EP1581618A2

EP1581618A2 - Therapeutic polypeptides, nucleic acids encoding same, and methods of use

Info

Publication number: EP1581618A2
Application number: EP03747643A
Authority: EP
Inventors: Enrique Alvarez; David W. Anderson; Ferenc L. Boldog; Elina Catterton; Shlomit R. Edinger; Elma R. Fernandes; Valerie L. Gerlach; Linda Gorman; William M. Grosse; Xiaojia Guo; Weizhen Ji; Ramesh Kekuda; Li Li; John R. Macdougall; Muralidhara Padigaru; Meera Patturajan; Jeffrey D. Peterson; Luca Rastelli; Richard A. Shimkets; David J. Stone
Original assignee: CuraGen Corp
Current assignee: CuraGen Corp
Priority date: 2002-05-02
Filing date: 2003-05-02
Publication date: 2005-10-05
Also published as: WO2003093432A3; WO2003093432A2; AU2003232034A1; CA2485089A1

Abstract

The present invention provides novel isolated polynucleotides and small molecule target polypeptides encoded by the polynucleotides. Antibodies that immunospecifically bind to a novel small molecule target polypeptide or any derivative, variant, mutant or fragment of that polypeptide, polynucleotide or antibody are disclosed, as are methods in which the small molecule target polypeptide, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states. More specifically, the present invention discloses methods of using recombinantly expressed and/or endogenously expressed proteins in various screening procedures for the purpose of identifying therapeutic antibodies and therapeutic small molecules associated with diseases. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

Description

THERAPEUTIC POLYPEPTIDES, NUCLEIC ACIDS ENCODING SAME, AND METHODS OF USE

FIELD OF THE INVENTION

The present invention relates to both novel polypeptides, and the nucleic acids encoding them as well as polypeptides that are targets of small molecule drugs. Those polypeptides have properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.

BACKGROUND OF THE INVENTION

Eukaryotic ceils are characterized by biochemical and physiological processes which under normal conditions are exquisitely balanced to achieve the preservation and propagation of the cells. When such cells are components of multicellular organisms such as vertebrates, or more particularly organisms such as mammals, the regulation of the biochemical and physiological processes involves intricate signaling pathways. Frequently, such signaling pathways involve extracellular signaling proteins, cellular receptors that bind the signaling proteins, and signal transducing components located within the cells.

Signaling proteins may be classified as endocrine effectors, paracrine effectors or autocrine effectors. Endocrine effectors are signaling molecules secreted by a given organ into the circulatory system, which are then transported to a distant target organ or tissue. The target cells include the receptors for the endocrine effector, and when the endocrine effector binds, a signaling cascade is induced. Paracrine effectors involve secreting cells and receptor cells in close proximity to each other, for example two different classes of cells in the same tissue or organ. One class of cells secretes the paracrine effector, which then reaches the second class of cells, for example by diffusion through the extracellular fluid. The second class of cells contains the receptors for the paracrine effector; binding of the effector results in induction of the signaling cascade that elicits the corresponding biochemical or physiological effect. Autocrine effectors are highly analogous to paracrine effectors, except that the same cell type that secretes the autocrine effector also contains the receptor. Thus the autocrine effector binds to receptors on the same cell, or on identical neighboring cells. The binding process then elicits the characteristic biochemical or physiological effect.

Signaling processes may elicit a variety of effects on cells and tissues including by way of nonlimiting example induction of cell or tissue proliferation, suppression of growth or proliferation, induction of differentiation or maturation of a cell or tissue, and suppression of differentiation or maturation of a cell or tissue.

Many pathological conditions involve dysregulation of expression of important effector proteins. In certain classes of pathologies the dysregulation is manifested as diminished or suppressed level of synthesis and secretion of protein effectors. In other classes of pathologies the dysregulation is manifested as increased or up-regulated level of synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by altered or mis-regulated levels of a protein effector of interest. Therefore there is a need to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There also is a need to provide the protein effector as a product of manufacture. Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest. In addition, there is a need for a method of treatment of a pathological condition brought on by a increased or up-regulated levels of the protein effector of interest.

Small molecule targets have been implicated in various disease states or pathologies. These targets may be proteins, and particularly enzymatic proteins, which are acted upon by small molecule drugs for the purpose of altering target function and achieving a desired result. Cellular, animal and clinical studies can be performed to elucidate the genetic contribution to the etiology and pathogenesis of conditions in which small molecule targets are implicated in a variety of physiologic, pharmacologic or native states. These studies utilize the core technologies at CuraGen Corporation to look at differential gene expression, protein-protein interactions, large-scale sequencing of expressed genes and the association of genetic variations such as, but not limited to, single nucleotide polymorphisms (SNPs) or splice variants in and between biological samples from experimental and control groups. The goal of such studies is to identify potential avenues for therapeutic intervention in order to prevent, treat the consequences or cure the conditions.

In order to treat diseases, pathologies and other abnormal states or conditions in which a mammalian organism has been diagnosed as being, or as being at risk for becoming, other than in a normal state or condition, it is important to identify new therapeutic agents. Such a procedure includes at least the steps of identifying a target component within an affected tissue or organ, and identifying a candidate therapeutic agent that modulates the functional attributes of the target. The target component may be any biological macromolecule implicated in the disease or pathology. Commonly the target is a polypeptide or protein with specific functional attributes. Other classes of macromolecule may be a nucleic acid, a polysaccharide, a lipid such as a complex lipid or a glycolipid; in addition a target may be a sub-cellular structure or extra-cellular structure that is comprised of more than one of these classes of macromolecule. Once such a target has been identified, it may be employed in a screening assay in order to identify favorable candidate therapeutic agents from among a large population of substances or compounds. Antibodies are multichain proteins that bind specifically to a given antigen, and bind poorly, or not at all, to substances deemed not to be cognate antigens. Antibodies are comprised of two short chains termed light chains and two long chains termed heavy chains. These chains are constituted of immunoglobulin domains, of which generally there are two classes: one variable domain per chain, one constant domain in light chains, and three or more constant domains in heavy chains. The antigen-specific portion of the immunoglobulin molecules resides in the variable domains; the variable domains of one light chain and one heavy chain associate with each other to generate the antigen-binding moiety. Antibodies that bind immunospecifically to a cognate or target antigen bind with high affinities. Accordingly, they are useful in assaying specifically for the presence of the antigen in a sample. In addition, they have the potential of inactivating the activity of the antigen.

Therefore there is a need to assay for the level of a protein effector of interest in a biological sample from such a subject, and to compare this level with that characteristic of a nonpathological condition. In particular, there is a need for such an assay based on the use of an antibody that binds immunospecifically to the antigen. There further is a need to inhibit the activity of the protein effector in cases where a pathological condition arises from elevated or excessive levels of the effector based on the use of an antibody that binds immunospecifically to the effector. Thus, there is a need for the antibody as a product of manufacture. There further is a need for a method of treatment of a pathological condition brought on by an elevated or excessive level of the protein effector of interest based on administering the antibody to the subject.

SUMMARY OF THE INVENTION

The invention is based in part upon the discovery of isolated polypeptides including amino acid sequences selected from mature forms of the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174. The novel nucleic acids and polypeptides are referred to herein as NOVla, NONlb, ΝOVlc, ΝONld, ΝOV2a, NOV2b, NOV2c, NOV2d, NON3a, ΝON3b, etc. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as "ΝONX" nucleic acid or polypeptide sequences.

The invention also is based in part upon variants of a mature form of the amino acid sequence selected from the group consisting of SEQ ID ΝO:2n, wherein n is an integer between 1 and 174, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. In another embodiment, the invention includes the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174. In another embodiment, the invention also comprises variants of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. The invention also involves fragments of any of the mature forms of the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, or any other amino acid sequence selected from this group. The invention also comprises fragments from these groups in which up to 15% of the residues are changed.

In another embodiment, the invention encompasses polypeptides that are naturally occurring allelic variants of the sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174. These allelic variants include amino acid sequences that are the translations of nucleic acid sequences differing by a single nucleotide from nucleic acid sequences selected from the group consisting of SEQ ID NOS: 2n-l, wherein n is an integer between 1 and 174. The variant polypeptide where any amino acid changed in the chosen sequence is changed to provide a conservative substitution.

In another embodiment, the invention comprises a pharmaceutical composition involving a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 and a pharmaceutically acceptable carrier. In another embodiment, the invention involves a kit, including, in one or more containers, this pharmaceutical composition.

In another embodiment, the invention includes the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease being selected from a pathology associated with a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 wherein said therapeutic is the polypeptide selected from this group.

In another embodiment, the invention comprises a method for determining the presence or amount of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 in a sample, the method involving providing the sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the polypeptide, thereby determining the presence or amount of polypeptide in the sample.

In another embodiment, the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 in a first mammalian subject, the method involving measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in this sample to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

In another embodiment, the invention involves a method of identifying an agent that binds to a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. The agent could be a cellular receptor or a downstream effector.

In another embodiment, the invention involves a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including providing a cell expressing the polypeptide of the invention and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent.

In another embodiment, the invention involves a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of the invention, wherein the test animal recombinantly expresses the polypeptide of the invention; measuring the activity of the polypeptide in the test animal after administering the test compound; and comparing the activity of the protein in the test animal with the activity of the polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the polypeptide of the invention. The recombinant test animal could express a test protein transgene or express the transgene under the control of a promoter at an increased level relative to a wild-type test animal The promoter may or may not b the native gene promoter of the transgene.

In another embodiment, the invention involves a method for modulating the activity of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including introducing a cell sample expressing the polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.

In another embodiment, the invention involves a method of treating or preventing a pathology associated with a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including administering the polypeptide to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject. The subject could be human.

In another embodiment, the invention involves a method of treating a pathological state in a mammal, the method including administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 or a biologically active fragment thereof.

In another embodiment, the invention involves an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide having an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174; a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174; a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 or any variant of the polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and the complement of any of the nucleic acid molecules.

In another embodiment, the invention comprises an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant.

In another embodiment,' the invention involves an isolated nucleic acid molecule including a nucleic acid sequence encoding a polypeptide having an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174 that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.

In another embodiment, the invention comprises an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 2n-l, wherein n is an integer between 1 and 174.

In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of the nucleotide sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174; a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174; and a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.

In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174, or a complement of the nucleotide sequence.

In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the nucleic acid molecule has a nucleotide sequence in which any nucleotide specified in the coding sequence of the chosen nucleotide sequence is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides in the chosen coding sequence are so changed, an isolated second polynucleotide that is a complement of the first polynucleotide, or a fragment of any of them.

In another embodiment, the invention includes a vector involving the nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174. This vector can have a promoter operably linked to the nucleic acid molecule. This vector can be located within a cell.

In another embodiment, the invention involves a method for determining the presence or amount of a nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174 in a sample, the method including providing the sample; introducing the sample to a probe that binds to the nucleic acid molecule; and determining the presence or amount of the probe bound to the nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in the sample. The presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type. The cell type can be cancerous.

In another embodiment, the invention involves a method for determining the presence of or predisposition for a disease associated with altered levels of a nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174 in a first mammalian subject, the method including measuring the amount of the nucleic acid in a sample from the first mammalian subject; and comparing the amount of the nucleic acid in the sample of step (a) to the amount of the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

The invention further provides an antibody that binds immunospecifically to a NOVX polypeptide. The NOVX antibody may be monoclonal, humanized, or a fully human antibody. Preferably, the antibody has a dissociation constant for the binding of the NOVX polypeptide to the antibody less than 1 x 10^"9 M. More preferably, the NOVX antibody neutralizes the activity of the NOVX polypeptide.

In a further aspect, the invention provides for the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, associated with a NOVX polypeptide. Preferably the therapeutic is a NOVX antibody.

In yet a further aspect, the invention provides a method of treating or preventing a NOVX-associated disorder, a method of treating a pathological state in a mammal, and a method of treating or preventing a pathology associated with a polypeptide by administering a NOVX antibody to a subject in an amount sufficient to treat or prevent the disorder.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting.

Other features and advantages of the invention will be apparent from the following detailed description and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a bar diagram showing the activation of 786-0 epithelial cell BrdU incorporation by CG51051-06 protein.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as "NOVX nucleic acids" or "NOVX polynucleotides" and the corresponding encoded polypeptides are referred to as "NOVX polypeptides" or "NOVX proteins." Unless indicated otherwise, "NOVX" is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.

Table A indicates the homology of NOVX polypeptides to known protein families. Thus, the nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table A will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table A.

Pathologies, diseases, disorders and condition and the like that are associated with NOVX sequences include, but are not limited to: e g., cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), vascular calcification, fibrosis, atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, metabolic disturbances associated with obesity, transplantation, osteoarthritis, rheumatoid arthritis, osteochondrodysplasia, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, ute s cancer, fertility, glomerulonephritis, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, psoriasis, skin disorders, graft versus host disease, AIDS, bronchial asthma, lupus, Crohn's disease; inflammatory bowel disease, ulcerative colitis, multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, schizophrenia, depression, asthma, emphysema, allergies, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation, neuroprotection, fertility, or regeneration (in vitro and in vivo).

NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.

Consistent with other known members of the family of proteins, identified in column 5 of Table A, the NOVX polypeptides of the present invention show homology to, and contain domains that are characteristic of, other members of such protein families. Details of the sequence relatedness and domain analysis for each NOVX are presented in Example A.

The NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function. Specifically, the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit diseases associated with the protein families listed in Table A.

The NOVX nucleic acids and polypeptides are also useful for detecting specific cell types. Details of the expression analysis for each NOVX are presented in Example C. Accordingly, the NOVX nucleic acids, polypeptides, antibodies and related compounds according to the invention will have diagnostic and therapeutic applications in the detection of a variety of diseases with differential expression in normal vs. diseased tissues, e.g. detection of a variety of cancers.

Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

NOVX clones

The NOVX genes and their corresponding encoded proteins are useful for preventing, treating or ameliorating medical conditions, e.g. , by protein or gene therapy. Pathological conditions can be diagnosed by determining the amount of the new protein in a sample or by determining the presence of mutations in the new genes. Specific uses are described for each of the NOVX genes, based on the tissues in which they are most highly expressed. Uses include developing products for the diagnosis or treatment of a variety of diseases and disorders.

The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. These include serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) a biological defense weapon.

In one specific embodiment, the invention includes an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 174; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 174, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) an amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 174; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; and (e) a fragment of any of (a) through (d).

In another specific embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 174; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 174 wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 174; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 174, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; (e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 174 or any variant of said polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and (f) the complement of any of said nucleic acid molecules.

In yet another specific embodiment, the invention includes an isolated nucleic acid molecule, wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 174; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 174 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; (c) a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 174; and (d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 174 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.

NOVX Nucleic Acids and Polypeptides

One aspect of the invention pertains to isolated nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e.g., NOVX mRNAs) and fragments for use as PCR primers for the amplification and/or mutation of NOVX nucleic acid molecules. As used herein, the term "nucleic acid molecule" is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof. The nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double-stranded DNA.

A NOVX nucleic acid can encode a mature NOVX polypeptide. As used herein, a "mature" form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product encoded by the corresponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product "mature" form arises, by way of nonlimiting example, as a result of one or more naturally occurring processing steps that may take place within the cell (e.g., host cell) in which the gene product arises. Examples of such processing steps leading to a "mature" form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+l to residue N remaining. Further as used herein, a "mature" form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.

The term "probe", as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single- stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.

The term "isolated" nucleic acid molecule, as used herein, is a nucleic acid that is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an "isolated" nucleic acid is free of sequences which naturally flank the nucleic acid (t^'.e., sequences located at the 5'- and 3 '-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an "isolated" nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium, or of chemical precursors or other chemicals.

A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, or a complement of this nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, as a hybridization probe, NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), MOLECULAR CLONING: A LABORATORY MANUAL 2^nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989; and Ausubel, et al, (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993.)

A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template with appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.

As used herein, the term "oligonucleotide" refers to a series of linked nucleotide residues. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of a NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2π-l, wherein n is an integer between 1 and 174, that it can hydrogen bond with few or no mismatches to the nucleotide sequence shown in SEQ ID NO:2rø-l, wherein n is an integer between 1 and 174, thereby forming a stable duplex.

As used herein, the term "complementary" refers to Watson-Crick or Hoogsteen base pairing between nucleotides units of a nucleic acid molecule, and the term "binding" means the physical or chemical interaction between two polypeptides or compounds or associated polypeptides or compounds or combinations thereof. Binding includes ionic, non-ionic, van der Waals, hydrophobic interactions, and the like. A physical interaction can be either direct or indirect. Indirect interactions may be through or due to the effects of another polypeptide or compound. Direct binding refers to interactions that do not take place through, or due to, the effect of another polypeptide or compound, but instead are without other substantial chemical intermediates.

A "fragment" provided herein is defined as a sequence of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, and is at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice.

A full-length NOVX clone is identified as containing an ATG translation start codon and an in-frame stop codon. Any disclosed NOVX nucleotide sequence lacking an ATG start codon therefore encodes a truncated C-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 5' direction of the disclosed sequence. Any disclosed NOVX nucleotide sequence lacking an in-frame stop codon similarly encodes a truncated N-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 3' direction of the disclosed sequence.

A "derivative" is a nucleic acid sequence or amino acid sequence formed from the native compounds either directly, by modification or partial substitution. An "analog" is a nucleic acid sequence or amino acid sequence that has a stmcture similar to, but not identical to, the native compound, e.g. they differs from it in respect to certain components or side chains. Analogs may be synthetic or derived from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. A "homolog" is a nucleic acid sequence or amino acid sequence of a particular gene that is derived from different species.

Derivatives and analogs may be full length or other than full length. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the proteins under stringent, moderately stringent, or low stringent conditions. See e.g. Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993, and below.

A "homologous nucleic acid sequence" or "homologous amino acid sequence," or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences include those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for a NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO:2n-l, wherein n is an integer between 1 and 174, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

A NOVX polypeptide is encoded by the open reading frame ("ORF") of a NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG "start" codon and terminates with one of the three "stop" codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bonafide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.

The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g. from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174; or an anti-sense strand nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174; or of a naturally occurring mutant of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174.

Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe has a detectable label attached, e.g. the label can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express a NOVX protein, such as by measuring a level of a NOVX-encoding nucleic acid in a sample of cells from a subject e.g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.

"A polypeptide having a biologically-active portion of a NOVX polypeptide" refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a "biologically-active portion of NOVX" can be prepared by isolating a portion of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, that encodes a polypeptide having a NOVX biological activity (the biological activities of the NOVX proteins are described below), expressing the encoded portion of NOVX protein (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of NOVX.

NOVX Single Nucleotide Polymorphisms

Variant sequences are also included in this application. A variant sequence can include a single nucleotide polymorphism (SNP). A SNP can, in some instances, be referred to as a "cSNP" to denote that the nucleotide sequence containing the SNP originates as a cDNA. A SNP can arise in several ways. For example, a SNP may be due to a substitution of one nucleotide for another at the polymorphic site. Such a substitution can be either a transition or a transversion. A SNP can also arise from a deletion of a nucleotide or an insertion of a nucleotide, relative to a reference allele. In this case, the polymorphic site is a site at which one allele bears a gap with respect to a particular nucleotide in another allele. SNPs occurring within genes may result in an alteration of the amino acid encoded by the gene at the position of the SNP. Intragenic SNPs may also be silent, when a codon including a SNP encodes the same amino acid as a result of the redundancy of the genetic code. SNPs occurring outside the region of a gene, or in an intron within a gene, do not result in changes in any amino acid sequence of a protein but may result in altered regulation of the expression pattern. Examples include alteration in temporal expression, physiological response regulation, cell type expression regulation, intensity of expression, and stability of transcribed message.

SeqCalling assemblies produced by the exon linking process were selected and extended using the following criteria. Genomic clones having regions with 98% identity to all or part of the initial or extended sequence were identified by BLASTN searches using the relevant sequence to query human genomic databases. The genomic clones that resulted were selected for further analysis because this identity indicates that these clones contain the genomic locus for these SeqCalling assemblies. These sequences were analyzed for putative coding regions as well as for similarity to the known DNA and protein sequences. Programs used for these analyses include Grail, Genscan, BLAST, HMMER, FASTA, Hybrid and other relevant programs.

Some additional genomic regions may have also been identified because selected SeqCalling assemblies map to those regions. Such SeqCalling sequences may have overlapped with regions defined by homology or exon prediction. They may also be included because the location of the fragment was in the vicinity of genomic regions identified by similarity or exon prediction that had been included in the original predicted sequence. The sequence so identified was manually assembled and then may have been extended using one or more additional sequences taken from CuraGen Corporation's human SeqCalling database. SeqCalling fragments suitable for inclusion were identified by the CuraTools™ program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed.

The regions defined by the procedures described above were then manually integrated and corrected for apparent inconsistencies that may have arisen, for example, from miscalled bases in the original fragments or from discrepancies between predicted exon junctions, EST locations and regions of sequence similarity, to derive the final sequence disclosed herein. When necessary, the process to identify and analyze SeqCalling assemblies and genomic clones was reiterated to derive the full length sequence (Alderbom et al., Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).

Variants are reported individually but any combination of all or a select subset of variants are also included as contemplated NOVX embodiments of the invention.

NOVX Nucleic Acid and Polypeptide Variants

The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO:2«, wherein n is an integer between 1 and 174.

In addition to the human NOVX nucleotide sequences of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, it will be appreciated by those skilled in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e.g. , the human population). Such genetic polymorphism in the NOVX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms "gene" and "recombinant gene" refer to nucleic acid molecules comprising an open reading frame (ORF) encoding a NOVX protein, preferably a vertebrate NOVX protein. Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the NOVX genes. Any and all such nucleotide variations and resulting amino acid polymorphisms in the NOVX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the NOVX polypeptides, are intended to be within the scope of the invention.

Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from a human SEQ ID NO:2n-l, wherein n is an integer between 1 and 174, are intended to be within the scope of the invention. Nucleic acid molecules corresponding to natural allelic variants and homologues of the NOVX cDNAs of the invention can be isolated based on their homology to the human NOVX nucleic acids disclosed herein using the human cDNAs, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions.

Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term "hybridizes under stringent conditions" is intended to describe conditions for hybridization and washing under which nucleotide sequences at least about 65% homologous to each other typically remain hybridized to each other.

Homologs (i.e., nucleic acids encoding NOVX proteins derived from species other than human) or other related sequences (e.g., paralogs) can be obtained by low, moderate or high stringency hybridization with all or a portion of the particular human sequence as a probe using methods well known in the art for nucleic acid hybridization and cloning.

As used herein, the phrase "stringent hybridization conditions" refers to conditions under which a probe, primer or oligonucleotide will hybridize to its target sequence, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5 °C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30 °C for short probes, primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about 60 °C for longer probes, primers and oligonucleotides. Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide.

Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6X SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg ml denatured salmon sperm DNA at 65°C, followed by one or more washes in 0.2X SSC, 0.01% BSA at 50°C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, corresponds to a naturally-occurring nucleic acid molecule. As used herein, a "naturally-occurring" nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein).

In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6X SSC, 5X Reinhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55 °C, followed by one or more washes in IX SSC, 0.1% SDS at 37 °C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Krieger, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY.

In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5X SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40°C, followed by one or more washes in 2X SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50°C. Other conditions of low stringency that may be . used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78: 6789-6792.

Conservative Mutations

In addition to naturally-occurring allelic variants of NOVX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174, thereby leading to changes in the amino acid sequences of the encoded NOVX protein, without altering the functional ability of that NOVX protein. For example, nucleotide substitutions leading to amino acid substitutions at "non-essential" amino acid residues can be made in the sequence of SEQ ID NO:2«, wherein n is an integer between 1 and 174. A "non-essential" amino acid residue is a residue that can be altered from the wild-type sequences of the NOVX proteins without altering their biological activity, whereas an "essential" amino acid residue is required for such biological activity. For example, amino acid residues that are conserved among the NOVX proteins of the invention are predicted to be particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.

Another aspect of the invention pertains to nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity. Such NOVX proteins differ in amino acid sequence from SEQ ID NO:2rc-l, wherein n is an integer between 1 and 174, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 40% homologous to the amino acid sequences of SEQ ID NO:2«, wherein n is an integer between 1 and 174. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NO :2w, wherein n is an integer between 1 and 174; more preferably at least about 70% homologous to SEQ ID NO:2«, wherein n is an integer between 1 and 174; still more preferably at least about 80% homologous to SEQ ID NO:2«, wherein n is an integer between 1 and 174; even more preferably at least about 90%) homologous to SEQ ID NO:2«, wherein n is an integer between 1 and 174; and most preferably at least about 95% homologous to SEQ ID NO:2M, wherein n is an integer between 1 and 174.

An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 174, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

Mutations can be introduced any one of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted, non-essential amino acid residues. A "conservative amino acid substitution" is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art. These families include amino acids with basic side chains (e.g. , lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis of a nucleic acid of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

The relatedness of amino acid families may also be determined based on side chain interactions. Substituted amino acids may be fully conserved "strong" residues or fully conserved "weak" residues. The "strong" group of conserved amino acid residues may be any one of the following groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other. Likewise, the "weak" group of conserved residues may be any one of the following: CSA, ATV, SAG, STNK, STPA, SGND, SNDEQK, NDEQHK, NEQHRK, HF Y, wherein the letters within each group represent the single letter amino acid code.

In one embodiment, a mutant NOVX protein can be assayed for (i) the ability to form proteimprotein interactions with other NOVX proteins, other cell-surface proteins, or biologically-active portions thereof, (ii) complex formation between a mutant NOVX protein and a NOVX ligand; or (iii) the ability of a mutant NOVX protein to bind to an intracellular target protein or biologically-active portion thereof; (e.g. avidin proteins).

In yet another embodiment, a mutant NOVX protein can be assayed for the ability to regulate a specific biological function (e.g., regulation of insulin release).

Interfering RNA

In one aspect of the invention, NOVX gene expression can be attenuated by RNA interference. One approach well-known in the art is short interfering RNA (siRNA) mediated gene silencing where expression products of a NOVX gene are targeted by specific double stranded NOVX derived siRNA nucleotide sequences that are complementary to at least a 19-25 nt long segment of the NOVX gene transcript, including the 5' untranslated (UT) region, the ORF, or the 3' UT region. See, e.g., PCT applications WO00/44895, WO99/32619, WOOl/75164, WOOl/92513, WO 01/29058, WOOl/89304, WO02/16620, and WO02/29858, each incorporated by reference herein in their entirety. Targeted genes can be a NOVX gene, or an upstream or downstream modulator of the NOVX gene. Nonlimiting examples of upstream or downstream modulators of a NOVX gene include, e.g., a transcription factor that binds the NOVX gene promoter, a kinase or phosphatase that interacts with a NOVX polypeptide, and polypeptides involved in a NOVX regulatory pathway.

According to the methods of the present invention, NOVX gene expression is silenced using short interfering RNA. A NOVX polynucleotide according to the invention includes a siRNA polynucleotide. Such a NOVX siRNA can be obtained using a NOVX polynucleotide sequence, for example, by processing the NOVX ribopolynucleotide sequence in a cell-free system, such as but not limited to a Drosophila extract, or by transcription of recombinant double stranded NOVX RNA or by chemical synthesis of nucleotide sequences homologous to a NOVX sequence. See, e.g., Tuschl, Zamore, Lehmann, Barrel and Sharp (1999), Genes & Dev. 13: 3191-3197, incorporated herein by reference in its entirety. When synthesized, a typical 0.2 micromolar-scale RNA synthesis provides about 1 milligram of siRNA, which is sufficient for 1000 transfection experiments using a 24-well tissue culture plate format. The most efficient silencing is generally observed with siRNA duplexes composed of a 21-nt sense strand and a 21-nt antisense strand, paired in a manner to have a 2-nt 3' overhang. The sequence of the 2-nt 3' overhang makes an additional small contribution to the specificity of siRNA target recognition. The contribution to specificity is localized to the unpaired nucleotide adjacent to the first paired bases. In one embodiment, the nucleotides in the 3' overhang are ribonucleotides. In an alternative embodiment, the nucleotides in the 3' overhang are deoxyribonucleotides. Using 2'-deoxyribonucleotides in the 3' overhangs is as efficient as using ribonucleotides, but deoxyribonucleotides are often cheaper to synthesize and are most likely more nuclease resistant.

A contemplated recombinant expression vector of the invention comprises a NOVX DNA molecule cloned into an expression vector comprising operatively-linked regulatory sequences flanking the NOVX sequence in a manner that allows for expression (by transcription of the DNA molecule) of both strands. An RNA molecule that is antisense to NOVX mRNA is transcribed by a first promoter (e.g., a promoter sequence 3' of the cloned DNA) and an RNA molecule that is the sense strand for the NOVX mRNA is transcribed by a second promoter (e.g., a promoter sequence 5' of the cloned DNA). The sense and antisense strands may hybridize in vivo to generate siRNA constructs for silencing of the NOVX gene. Alternatively, two constmcts can be utilized to create the sense and anti-sense strands of a siRNA constmct. Finally, cloned DNA can encode a constmct having secondary structure, wherein a single transcript has both the sense and complementary antisense sequences from the target gene or genes. In an example of this embodiment, a hairpin RNAi product is homologous to all or a portion of the target gene. In another example, a hairpin RNAi product is a siRNA. The regulatory sequences flanking the NOVX sequence may be identical or may be different, such that their expression may be modulated independently, or in a temporal or spatial manner.

In a specific embodiment, siRNAs are transcribed intracellularly by cloning the NOVX gene templates into a vector containing, e.g., a RNA pol III transcription unit from the smaller nuclear RNA (snRNA) U6 or the human RNase P RNA HI. One example of a vector system is the GeneSuppressor™ RNA Interference kit (commercially available from Imgenex). The U6 and HI promoters are members of the type III class of Pol III promoters. The +1 nucleotide of the U6-like promoters is always guanosine, whereas the +1 for HI promoters is adenosine. The termination signal for these promoters is defined by five consecutive thymidines. The transcript is typically cleaved after the second uridine. Cleavage at this position generates a 3' UU overhang in the expressed siRNA, which is similar to the 3' overhangs of synthetic siRNAs. Any sequence less than 400 nucleotides in length can be transcribed by these promoter, therefore they are ideally suited for the expression of around 21 -nucleotide siRNAs in, e.g., an approximately 50-nucleotide RNA stem-loop transcript.

A siRNA vector appears to have an advantage over synthetic siRNAs where long term knock-down of expression is desired. Cells transfected with a siRNA expression vector would experience steady, long-term mRNA inhibition. In contrast, cells transfected with exogenous synthetic siRNAs typically recover from mRNA suppression within seven days or ten rounds of cell division. The long-term gene silencing ability of siRNA expression vectors may provide for applications in gene therapy.

In general, siRNAs are chopped from longer dsRNA by an ATP-dependent ribonuclease called DICER. DICER is a member of the RNase III family of double-stranded RNA-specific endonucleases. The siRNAs assemble with cellular proteins into an endonuclease complex. In vitro studies in Drosophila suggest that the siRNAs/protein complex (siRNP) is then transferred to a second enzyme complex, called an RNA-induced silencing complex (RISC), which contains an endoribonuclease that is distinct from DICER. RISC uses the sequence encoded by the antisense siRNA strand to find and destroy mRNAs of complementary sequence. The siRNA thus acts as a guide, restricting the ribonuclease to cleave only mRNAs complementary to one of the two siRNA strands.

A NOVX mRNA region to be targeted by siRNA is generally selected from a desired NOVX sequence beginning 50 tolOO nt downstream of the start codon. Alternatively, 5' or 3' UTRs and regions nearby the start codon can be used but are generally avoided, as these may be richer in regulatory protein binding sites. UTR-binding proteins and/or translation initiation complexes may interfere with binding of the siRNP or RISC endonuclease complex. An initial BLAST homology search for the selected siRNA sequence is done against an available nucleotide sequence library to ensure that only one gene is targeted. Specificity of target recognition by siRNA duplexes indicate that a single point mutation located in the paired region of an siRNA duplex is sufficient to abolish target mRNA degradation. See, Elbashir et al. 2001 EMBO J. 20(23):6877-88. Hence, consideration should be taken to accommodate SNPs, polymorphisms, allelic variants or species-specific variations when targeting a desired gene.

In one embodiment, a complete NOVX siRNA experiment includes the proper negative control. A negative control siRNA generally has the same nucleotide composition as the NOVX siRNA but lack significant sequence homology to the genome. Typically, one would scramble the nucleotide sequence of the NOVX siRNA and do a homology search to make sure it lacks homology to any other gene.

Two independent NOVX siRNA duplexes can be used to knock-down a target NOVX gene. This helps to control for specificity of the silencing effect. In addition, expression of two independent genes can be simultaneously knocked down by using equal concentrations of different NOVX siRNA duplexes, e.g., a NOVX siRNA and an siRNA for a regulator of a NOVX gene or polypeptide. Availability of siRNA-associating proteins is believed to be more limiting than target mRNA accessibility.

A targeted NOVX region is typically a sequence of two adenines (AA) and two thymidines (TT) divided by a spacer region of nineteen (N19) residues (e.g., AA(N19)TT). A desirable spacer region has a G/C-content of approximately 30% to 70%, and more preferably of about 50%. If the sequence AA(N19)TT is not present in the target sequence, an alternative target region would be AA(N21). The sequence of the NOVX sense siRNA corresponds to (N19)TT or N21, respectively. In the latter case, conversion of the 3' end of the sense siRNA to TT can be performed if such a sequence does not naturally occur in the NOVX polynucleotide. The rationale for this sequence conversion is to generate a symmetric duplex with respect to the sequence composition of the sense and antisense 3' overhangs. Symmetric 3' overhangs may help to ensure that the siRNPs are formed with approximately equal ratios of sense and antisense target RNA-cleaving siRNPs. See, e.g., Elbashir, Lendeckel and Tuschl (2001). Genes & Dev. 15: 188-200, incorporated by reference herein in its entirely. The modification of the overhang of the sense sequence of the siRNA duplex is not expected to affect targeted mRNA recognition, as the antisense siRNA strand guides target recognition.

Alternatively, if the NOVX target mRNA does not contain a suitable AA(N21) sequence, one may search for the sequence NA(N21). Further, the sequence of the sense strand and antisense strand may still be synthesized as 5' (N19)TT, as it is believed that the sequence of the 3 '-most nucleotide of the antisense siRNA does not contribute to specificity. Unlike antisense or ribozyme technology, the secondary structure of the target mRNA does not appear to have a strong effect on silencing. See, Harborth, et αl. (2001) J. Cell Science 114: 4557-4565, incoφorated by reference in its entirety.

Transfection of NOVX siRNA duplexes can be achieved using standard nucleic acid transfection methods, for example, OLIGOFECT AMINE Reagent (commercially available from Invitrogen). An assay for NOVX gene silencing is generally performed approximately 2 days after transfection. No NOVX gene silencing has been observed in the absence of transfection reagent, allowing for a comparative analysis of the wild-type and silenced NOVX phenotypes. In a specific embodiment, for one well of a 24-well plate, approximately 0.84 μg of the siRNA duplex is generally sufficient. Cells are typically seeded the previous day, and are transfected at about 50% confluence. The choice of cell culture media and conditions are routine to those of skill in the art, and will vary with the choice of cell type. The efficiency of transfection may depend on the cell type, but also on the passage number and the confluency of the cells. The time and the manner of formation of siRNA-liposome complexes (e.g. inversion versus vortexing) are also critical. Low transfection efficiencies are the most frequent cause of unsuccessful NOVX silencing. The efficiency of transfection needs to be carefully examined for each new cell line to be used. Preferred cell are derived from a mammal, more preferably from a rodent such as a rat or mouse, and most preferably from a human. Where used for therapeutic treatment, the cells are preferentially autologous, although non-autologous cell sources are also contemplated as within the scope of the present invention.

For a control experiment, transfection of 0.84 μg single-stranded sense NOVX siRNA will have no effect on NOVX silencing, and 0.84 μg antisense siRNA has a weak silencing effect when compared to 0.84 μg of duplex siRNAs. Control experiments again allow for a comparative analysis of the wild-type and silenced NOVX phenotypes. To control for transfection efficiency, targeting of common proteins is typically performed, for example targeting of lamin A/C or transfection of a CMV-driven EGFP-expression plasmid (e.g. commercially available from Clontech). In the above example, a determination of the fraction of lamin A/C knockdown in cells is determined the next day by such techniques as immunofluorescence, Western blot, Northern blot or other similar assays for protein expression or gene expression. Lamin A/C monoclonal antibodies may be obtained from Santa Cruz Biotechnology.

Depending on the abundance and the half life (or turnover) of the targeted NOVX polynucleotide in a cell, a knock-down phenotype may become apparent after 1 to 3 days, or even later. In cases where no NOVX knock-down phenotype is observed, depletion of the NOVX polynucleotide may be observed by immunofluorescence or Western blotting. If the NOVX polynucleotide is still abundant after 3 days, cells need to be split and transferred to a fresh 24-well plate for re-transfection. If no knock-down of the targeted protein is observed, it may be desirable to analyze whether the target mRNA (NOVX or a NOVX upstream or downstream gene) was effectively destroyed by the transfected siRNA duplex. Two days after transfection, total RNA is prepared, reverse transcribed using a target-specific primer, and PCR-amplified with a primer pair covering at least one exon-exon junction in order to control for amplification of pre-mRNAs. RT/PCR of a non-targeted mRNA is also needed as control. Effective depletion of the mRNA yet undetectable reduction of target protein may indicate that a large reservoir of stable NOVX protein may exist in the cell. Multiple transfection in sufficiently long intervals may be necessary until the target protein is finally depleted to a point where a phenotype may become apparent. If multiple transfection steps are required, cells are split 2 to 3 days after transfection. The cells may be transfected immediately after splitting.

An inventive therapeutic method of the invention contemplates administering a NOVX siRNA construct as therapy to compensate for increased or aberrant NOVX expression or activity. The NOVX ribopolynucleotide is obtained and processed into siRNA fragments, or a NOVX siRNA is synthesized, as described above. The NOVX siRNA is administered to cells or tissues using known nucleic acid transfection techniques, as described above. A NOVX siRNA specific for a NOVX gene will decrease or knockdown NOVX transcription products, which will lead to reduced NOVX polypeptide production, resulting in reduced NOVX polypeptide activity in the cells or tissues.

The present invention also encompasses a method of treating a disease or condition associated with the presence of a NOVX protein in an individual comprising administering to the individual an RNAi constmct that targets the mRNA of the protein (the mRNA that encodes the protein) for degradation. A specific RNAi construct includes a siRNA or a double stranded gene transcript that is processed into siRNAs. Upon treatment, the target protein is not produced or is not produced to the extent it would be in the absence of the treatment.

Where the NOVX gene function is not correlated with a known phenotype, a control sample of cells or tissues from healthy individuals provides a reference standard for determining NOVX expression levels. Expression levels are detected using the assays described, e.g., RT-PCR, Northern blotting, Western blotting, ELISA, and the like. A subject sample of cells or tissues is taken from a mammal, preferably a human subject, suffering from a disease state. The NOVX ribopolynucleotide is used to produce siRNA constructs, that are specific for the NOVX gene product. These cells or tissues are treated by administering NOVX siRNA' s to the cells or tissues by methods described for the transfection of nucleic acids into a cell or tissue, and a change in NOVX polypeptide or polynucleotide expression is observed in the subject sample relative to the control sample, using the assays described. This NOVX gene knockdown approach provides a rapid method for determination of a NOVX minus (NOVX^") phenotype in the treated subject sample. The NOVX^" phenotype observed in the treated subject sample thus serves as a marker for monitoring the course of a disease state during treatment.

In specific embodiments, a NOVX siRNA is used in therapy. Methods for the generation and use of a NOVX siRNA are known to those skilled in the art. Example techniques are provided below.

Production of RNAs

Sense RNA (ssRNA) and antisense RNA (asRNA) of NOVX are produced using known methods such as transcription in RNA expression vectors. In the initial experiments, the sense and antisense RNA are about 500 bases in length each. The produced ssRNA and asRNA (0.5 μM) in 10 mM Tris-HCl (pH 7.5) with 20 mM NaCl were heated to 95° C for 1 min then cooled and annealed at room temperature for 12 to 16 h. The RNAs are precipitated and resuspended in lysis buffer (below). To monitor annealing, RNAs are electrophoresed in a 2% agarose gel in TBE buffer and stained with ethidium bromide. See, e.g., Sambrook et al., Molecular Cloning. Cold Spring Harbor Laboratory Press, Plainview, N.Y. (1989).

Lysate Preparation

Untreated rabbit reticulocyte lysate (Ambion) are assembled according to the manufacturer's directions. dsRNA is incubated in the lysate at 30° C for 10 min prior to the addition of mRNAs. Then NOVX mRNAs are added and the incubation continued for an additional 60 min. The molar ratio of double stranded RNA and mRNA is about 200: 1. The NOVX mRNA is radiolabeled (using known techniques) and its stability is monitored by gel electrophoresis.

In a parallel experiment made with the same conditions, the double stranded RNA is internally radiolabeled with a ³²P-ATP. Reactions are stopped by the addition of 2 X proteinase K buffer and deproteinized as described previously (Tuschl et al., Genes Dev., 13:3191-3197 (1999)). Products are analyzed by electrophoresis in 15% or 18% polyacrylamide sequencing gels using appropriate RNA standards. By monitoring the gels for radioactivity, the natural production of 10 to 25 nt RNAs from the double stranded RNA can be determined.

The band of double stranded RNA, about 21-23 bps, is eluded. The efficacy of these 21-23 mers for suppressing NOVX transcription is assayed in vitro using the same rabbit reticulocyte assay described above using 50 nanomolar of double stranded 21-23 mer for each assay. The sequence of these 21-23 mers is then determined using standard nucleic acid sequencing techmques.

RNA Preparation

21 nt RNAs, based on the sequence determined above, are chemically synthesized using Expedite RNA phosphoramidites and thymidine phosphoramidite (Proligo, Germany). Synthetic oligonucleotides are deprotected and gel-purified (Elbashir, Lendeckel, & Tuschl, Genes & Dev. 15, 188-200 (2001)), followed by Sep-Pak C18 cartridge (Waters, Milford, Mass., USA) purification (Tuschl, et al., Biochemistry, 32:11658-11668 (1993)).

These RNAs (20 μM) single strands are incubated in annealing buffer (100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate) for 1 min at 90° C followed by 1 h at 37° C.

Cell Culture

A cell culture known in the art to regularly express NOVX is propagated using standard conditions. 24 hours before transfection, at approx. 80% confluency, the cells are trypsinized and diluted 1:5 with fresh medium without antibiotics (1-3 X 105 cells/ml) and transferred to 24-well plates (500 ml/well). Transfection is performed using a commercially available lipofection kit and NOVX expression is monitored using standard techniques with positive and negative control. A positive control is cells that naturally express NOVX while a negative control is cells that do not express NOVX. Base-paired 21 and 22 nt siRNAs with overhanging 3' ends mediate efficient sequence-specific mRNA degradation in lysates and in cell culture. Different concentrations of siRNAs are used. An efficient concentration for suppression in vitro in mammalian culture is between 25 nM to 100 nM final concentration. This indicates that siRNAs are effective at concentrations that are several orders of magnitude below the concentrations applied in conventional antisense or ribozyme gene targeting experiments.

The above method provides a way both for the deduction of NOVX siRNA sequence and the use of such siRNA for in vitro suppression. In vivo suppression may be performed using the same siRNA using well known in vivo transfection or gene therapy transfection techniques.

Antisense Nucleic Acids

Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2τι-l, wherein n is an integer between 1 and 174, or fragments, analogs or derivatives thereof. An "antisense" nucleic acid comprises a nucleotide sequence that is complementary to a "sense" nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of a NOVX protein of SEQ ID NO:2«, wherein n is an integer between 1 and 174, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, are additionally provided.

In one embodiment, an antisense nucleic acid molecule is antisense to a "coding region" of the coding strand of a nucleotide sequence encoding a NOVX protein. The term "coding region" refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a "noncoding region" of the coding strand of a nucleotide sequence encoding the NOVX protein. The term "noncoding region" refers to 5' and 3' sequences which flank the coding region that are not translated into amino acids (t.e., also referred to as 5' and 3' untranslated regions).

Given the coding strand sequences encoding the NOVX protein disclosed herein, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of NOVX mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of NOVX mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of NOVX mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids (e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used). Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5 -carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracii, beta-D-mannosylqueosine, 5'-methoxycarboxymethyluracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).

The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the maj or groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred. In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands mn parallel to each other. See, e.g., Gaultier, et al., 1987. Nucl. Acids Res. 15: 6625-6641. The antisense nucleic acid molecule can also comprise a 2^*-o-methylribonucleotide (See, e.g., Inoue, et al. 1987. Nucl. Acids Res. 15: 6131-6148) or a chimeric RNA-DNA analogue (See, e.g., Inoue, et al, 1987. FEBSLett. 215: 327-330.

Ribozymes and PNA Moieties

Nucleic acid modifications include, by way of non-limiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.

In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Geriach 1988. Nature 334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO:2Λ-1, wherein n is an integer between 1 and 174). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a NOVX-encoding mRNA. See, e.g., U.S. Patent 4,987,071 to Cech, et al. and U.S. Patent 5,116,742 to Cech, et al. NOVX mRNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel et al, (1993) Science 261:1411-1418.

Alternatively, NOVX gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the NOVX nucleic acid (e.g., the NOVX promoter and/or enhancers) to form triple helical stmctures that prevent transcription of the NOVX gene in target cells. See, e.g., Helene, 199 . Anticancer Drug Des. 6: 569-84; Helene, et al. 1992. Ann. NY. Acad. Sci. 660: 27-36; Maher, 1992. Bioassays 14: 807-15.

In various embodiments, the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e.g., Hyrup, et ah, 1996. Bioorg Med Chem 4: 5-23. As used herein, the terms "peptide nucleic acids" or "PNAs" refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleotide bases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomer can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al, 1996. supra; Perry-O'Keefe, et al., 1996. Proc. Natl. Acad. Sci. USA 93: 14670-14675.

PNAs of NOVX can be used in therapeutic and diagnostic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e.g., inducing transcription or translation arrest or inhibiting replication. PNAs of NOVX can also be used, for example, in the analysis of single base pair mutations in a gene (e.g., PNA directed PCR clamping; as artificial restriction enzymes when used in combination with other enzymes, e.g., S_\ nucleases (See, Hyrup, et al., I996.supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al., 1996, supra; Perry-O'Keefe, et al, 1996. supra).

In another embodiment, PNAs of NOVX can be modified, e.g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of NOVX can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes (e.g., RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleotide bases, and orientation (see, Hyrup, et al., 1996. supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al., 1996. supra and Finn, et al, 1996. Nucl Acids Res 24: 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g.,

5'-(4-methoxytrityl)amino-5'-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5* end of DNA. See, e.g., Mag, et al, 1989. Nucl Acid Res 17: 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5* PNA segment and a 3' DNA segment. See, e.g., Finn, et al, 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5' DNA segment and a 3' PNA segment. See, e.g., Petersen, et al, 1975. Bioorg. Med. Chem. Lett. 5: 1119-11124.

In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al, 1989. Proc. Natl. Acad. Sci. U.S.A. 86: 6553-6556; Lemaitre, et al, 1987. Proc. Natl. Acad. Sci. 84: 648-652; PCT Publication No. WO88/09810) or the blood-brain barrier (see, e.g. , PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e.g., Krol, etal, 1988. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988. Pharm. Res. 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.

NOVX Polypeptides

A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in any one of SEQ ID NO:2«, wherein n is an integer between 1 and 174. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in any one of SEQ ID NO:2«, wherein n is an integer between 1 and 174, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

In general, a NOVX variant that preserves NOVX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence. Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.

One aspect of the invention pertains to isolated NOVX proteins, and biologically-active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-NOVX antibodies. In one embodiment, native NOVX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, NOVX proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.

An "isolated" or "purified" polypeptide or protein or biologically-active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the NOVX protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language "substantially free of cellular material" includes preparations of NOVX proteins in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly-produced. In one embodiment, the language "substantially free of cellular material" includes preparations of NOVX proteins having less than about 30% (by dry weight) of non-NOVX proteins (also referred to herein as a "contaminating protein"), more preferably less than about 20% of non-NOVX proteins, still more preferably less than about 10% of non-NOVX proteins, and most preferably less than about 5% of non-NOVX proteins. When the NOVX protein or biologically-active portion thereof is recombinantly-produced, it is also preferably substantially free of culture medium, t.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the NOVX protein preparation.

The language "substantially free of chemical precursors or other chemicals" includes preparations of NOVX proteins in which the protein is separated from chemical precursors or other chemicals that are involved in the synthesis of the protein. In one embodiment, the language "substantially free of chemical precursors or other chemicals" includes preparations of NOVX proteins having less than about 30% (by dry weight) of chemical precursors or non-NOVX chemicals, more preferably less than about 20% chemical precursors or non-NOVX chemicals, still more preferably less than about 10% chemical precursors or non-NOVX chemicals, and most preferably less than about 5% chemical precursors or non-NOVX chemicals.

Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g., the amino acid sequence of SEQ ID NO:2«, wherein n is an integer between 1 and 174) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of a NOVX protein. Typically, biologically-active portions comprise a domain or motif with at least one activity of the NOVX protein. A biologically-active portion of a NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length. Moreover, other biologically-active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native NOVX protein.

In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2«, wherein n is an integer between 1 and 174. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2«, wherein n is an integer between 1 and 174, and retains the functional activity of the protein of SEQ ID NO:2«, wherein n is an integer between 1 and 174, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence of SEQ ID NO:2«, wherein n is an integer between 1 and 174, and retains the functional activity of the NOVX proteins of SEQ ID NO:2«, wherein n is an integer between 1 and 174.

Determining Homology Between Two or More Sequences

To determine the percent homology of two amino acid sequences or of two nucleic acids, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are homologous at that position (i.e., as used herein amino acid or nucleic acid "homology" is equivalent to amino acid or nucleic acid "identity").

The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970. JMol Biol 48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%), 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence of SEQ ID NO:2»-l, wherein n is an integer between 1 and 174.

The term "sequence identity" refers to the degree to which two polynucleotide or polypeptide sequences are identical on a residue-by-residue basis over a particular region of comparison. The term "percentage of sequence identity" is calculated by comparing two optimally aligned sequences over that region of comparison, determining the number of positions at which the identical nucleic acid base (e.g., A, T, C, G, U, or I, in the case of nucleic acids) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the region of comparison (i.e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity. The term "substantial identity" as used herein denotes a characteristic of a polynucleotide sequence, wherein the polynucleotide comprises a sequence that has at least 80 percent sequence identity, preferably at least 85 percent identity and often 90 to 95 percent sequence identity, more usually at least 99 percent sequence identity as compared to a reference sequence over a comparison region.

Chimeric and Fusion Proteins

The invention also provides NOVX chimeric or fusion proteins. As used herein, a NOVX "chimeric protein" or "fusion protein" comprises a NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An "NOVX polypeptide" refers to a polypeptide having an amino acid sequence corresponding to a NOVX protein of SEQ ID NO:2«, wherein n is an integer between 1 and 174, whereas a "non-NOVX polypeptide" refers to a polypeptide having an amino acid sequence corresponding to a protein that is not substantially homologous to the NOVX protein, e.g., a protein that is different from the NOVX protein and that is derived from the same or a different organism. Within a NOVX fusion protein the NOVX polypeptide can correspond to all or a portion of a NOVX protein. In one embodiment, a NOVX fusion protein comprises at least one biologically-active portion of a NOVX protein. In another embodiment, a NOVX fusion protein comprises at least two biologically-active portions of a NOVX protein. In yet another embodiment, a NOVX fusion protein comprises at least three biologically-active portions of a NOVX protein. Within the fusion protein, the term "operatively-linked" is intended to indicate that the NOVX polypeptide and the non-NOVX polypeptide are fused in-frame with one another. The non-NOVX polypeptide can be fused to the N-terminus or C-terminus of the NOVX polypeptide.

In one embodiment, the fusion protein is a GST-NO VX fusion protein in which the NOVX sequences are fused to the C-terminus of the GST (glutathione S-transferase) sequences. Such fusion proteins can facilitate the purification of recombinant NOVX polypeptides. In another embodiment, the fusion protein is a NOVX protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression and or secretion of NOVX can be increased through use of a heterologous signal sequence.

In yet another embodiment, the fusion protein is a NOVX-immunoglobulin fusion protein in which the NOVX sequences are fused to sequences derived from a member of the immunoglobulin protein family. The NOVX-immunoglobulin fusion proteins of the invention can be incoφorated into pharmaceutical compositions and administered to a subject to inhibit an interaction between a NOVX ligand and a NOVX protein on the surface of a cell, to thereby suppress NOVX-mediated signal transduction in vivo. The NOVX-immunoglobulin fusion proteins can be used to affect the bioavailability of a NOVX cognate ligand. Inhibition of the NOVX ligand/NOVX interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, as well as modulating (e.g. promoting or inhibiting) cell survival. Moreover, the NOVX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-NOVX antibodies in a subject, to purify NOVX ligands, and in screening assays to identify molecules that inhibit the interaction of NOVX with a NOVX ligand.

A NOVX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e.g., Ausubel, etal (eds.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). A NOVX-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the NOVX protein. NOVX Agonists and Antagonists

The invention also pertains to variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists. Variants of the NOVX protein can be generated by mutagenesis (e.g., discrete point mutation or truncation of the NOVX protein). An agonist of the NOVX protein can retain substantially the same, or a subset of, the biological activities of the naturally occurring form of the NOVX protein. An antagonist of the NOVX protein can inhibit one or more of the activities of the naturally occurring form of the NOVX protein by, for example, competitively binding to a downstream or upstream member of a cellular signaling cascade which includes the NOVX protein. Thus, specific biological effects can be elicited by treatment with a variant of limited function. In one embodiment, treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the protein has fewer side effects in a subject relative to treatment with the naturally occurring form of the NOVX proteins.

Variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists can be identified by screening combinatorial libraries of mutants (e.g. , truncation mutants) of the NOVX proteins for NOVX protein agonist or antagonist activity. In one embodiment, a variegated library of NOVX variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of NOVX variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential NOVX sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of NOVX sequences therein. There are a variety of methods which can be used to produce libraries of potential NOVX variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential NOVX sequences. Methods for synthesizing degenerate oligonucleotides are well-known within the art. See, e.g., Narang, 1983. Tetrahedron 39: 3; Itakura, et al, 1984. Annu. Rev. Biochem. 53: 323; Itakura, et al, 1984. Science 198: 1056; Ike, et al, 1983. Nucl. Acids Res. 11: 477. Polypeptide Libraries

In addition, libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of a NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pahs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S_t nuclease, and ligating the resulting fragment library into an expression vector. By this method, expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the NOVX proteins.

Various techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screemng cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of NOVX proteins. The most widely used techniques, which are amenable to high throughput analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique that enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify NOVX variants. See, e.g., Arkin and Yourvan, 1992. Proc. Natl. Acad. Sci. USA 89: 7811-7815; Delgrave, etal, 1993. Protein Engineering 6:321 -33 .

Anti-NOVX Antibodies

Included in the invention are antibodies to NOVX proteins, or fragments of NOVX proteins. The term "antibody" as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, t^'.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, F_ab, F_a ' and F(ab')2 fragments, and an F_ab expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgGj, IgG , and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.

An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecifically bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence of SEQ ID NO:2«, wherein n is an integer between 1 and 174, and encompasses an epitope thereof such that an antibody raised against the peptide forms a specific immune complex with the full length protein or with any fragment that contains the epitope. Preferably, the antigenic peptide comprises at least 10 amino acid residues, or at least 15 amino acid residues, or at least 20 amino acid residues, or at least 30 amino acid residues. Preferred epitopes encompassed by the antigenic peptide are regions of the protein that are located on its surface; commonly these are hydrophilic regions.

In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981, Proc. Nat. Acad. Sci. USA 78: 3824-3828; Kyte and Doolittle 1982, J Mol. Biol. 157: 105-142, each incoφorated herein by reference in their entirety. Antibodies that are specific for one or more domains within an antigenic protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

The term "epitope" includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. A NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (KD) is <1 μM, preferably < 100 nM, more preferably < 10 nM, and most preferably < 100 pM to about 1 pM, as measured by assays including radioligand binding assays or similar assays known to skilled artisans.

A protein of the invention, or a derivative, fragment, analog, homolog or ortholog thereof, may be utilized as an immunogen in the generation of antibodies that immunospecifically bind these protein components.

Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, incoφorated herein by reference). Some of these antibodies are discussed below.

Polyclonal Antibodies

For the production of polyclonal antibodies, various suitable host animals (e.g., rabbit, goat, mouse or other mammal) may be immunized by one or more injections with the native protein, a synthetic variant thereof, or a derivative of the foregoing. An appropriate immunogenic preparation can contain, for example, the naturally occurring immunogenic protein, a chemically synthesized polypeptide representing the immunogenic protein, or a recombinantly expressed immunogenic protein. Furthermore, the protein may be conjugated to a second protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. The preparation can further include an adjuvant. Various adjuvants used to increase the immunological response include, but are not limited to, Freund's (complete and incomplete), mineral gels (e.g., aluminum hydroxide), surface active substances (e.g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, etc.), adjuvants usable in humans such as Bacille Calmette-Guerin and Corynebacterium parvum, or similar immunostimulatory agents. Additional examples of adjuvants which can be employed include MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).

The polyclonal antibody molecules directed against the immunogenic protein can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as affinity chromatography using protein A or protein G, which provide primarily the IgG fraction of immune semm. Subsequently, or alternatively, the specific antigen which is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffinity chromatography. Purification of immunoglobulins is discussed, for example, by D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia PA, Vol. 14, No. 8 (April 17, 2000), pp. 25-28).

Monoclonal Antibodies

The term "monoclonal antibody" (MAb) or "monoclonal antibody composition", as used herein, refers to a population of antibody molecules that contain only one molecular species of antibody molecule consisting of a unique light chain gene product and a unique heavy chain gene product. In particular, the complementarity determining regions (CDRs) of the monoclonal antibody are identical in all the molecules of the population. MAbs thus contain an antigen binding site capable of immunoreacting with a particular epitope of the antigen characterized by a unique binding affinity for it.

Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro.

The immunizing agent will typically include the protein antigen, a fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice. Academic Press, (1986) pp. 59-103). Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells. Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, California and the American Type Culture Collection, Manassas, Virginia. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).

The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is an objective, especially important in therapeutic applications of monoclonal antibodies, to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen.

After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods (Goding,1986). Suitable culture media for this puφose include, for example, Dulbecco's Modified Eagle's Medium and RPMI- 1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.

The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.

The monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Patent No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S. Patent No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.

Humanized Antibodies

The antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin. Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')₂ or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., Nature, 321. -522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. (See also U.S. Patent No. 5,225,539.) In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies can also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)). Human Antibodies

Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed "human antibodies", or "fully human antibodies" herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Barr Vims in vitro (see Cole, et al, 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).

In addition, human antibodies can also be produced using additional techniques, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)). Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al. (Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature 368 856-859 (1994)); Morrison ( Nature 368, 812-13 (1994)); Fishwild et al,( Nature Biotechnology 14, 845-51 (1996)); Neuberger (Nature Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol. 13 65-93 (1995)).

Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal's endogenous antibodies in response to challenge by an antigen. (See PCT publication WO94/02602). The endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host's genome. The human genes are incoφorated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The preferred embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse™ as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.

An example of a method of producing a nonhuman host, exemplified as a mouse, lacking expression of an endogenous immunoglobulin heavy chain is disclosed in U.S. Patent No. 5,939,598. It can be obtained by a method including deleting the J segment genes from at least one endogenous heavy chain locus in an embryonic stem cell to prevent rearrangement of the locus and to prevent formation of a transcript of a rearranged immunoglobulin heavy chain locus, the deletion being effected by a targeting vector containing a gene encoding a selectable marker; and producing from the embryonic stem cell a transgenic mouse whose somatic and germ cells contain the gene encoding the selectable marker.

A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Patent No. 5,916,771. It includes introducing an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell. The hybrid cell expresses an antibody containing the heavy chain and the light chain.

In a further improvement on this procedure, a method for identifying a clinically relevant epitope on an immunogen, and a correlative method for selecting an antibody that binds immunospecifically to the relevant epitope with high affinity, are disclosed in PCT publication WO 99/53049.

F_ab Fragments and Single Chain Antibodies

According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Patent No. 4,946,778). In addition, methods can be adapted for the construction of F_ab expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal F_ab fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof. Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F^yμ fragment produced by pepsin digestion of an antibody molecule; (ii) an F_ab fragment generated by reducing the disulfide bridges of an F(_ab-)₂ fragment; (iii) an F_ab fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) F_v fragments.

Bispecific Antibodies

Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for an antigenic protein of the invention. The second binding target is any other antigen, and advantageously is a cell-surface protein or receptor or receptor subunit.

Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture often different antibody molecules, of which only one has the correct bispecific stmcture. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published 13 May 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).

Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CHI) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121:210 (1986).

According to another approach described in WO 96/27011, the interface between a pah of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture. The preferred interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.

Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab') bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al., Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab')₂ fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab' fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab'-TNB derivatives is then reconverted to the Fab' -thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab'-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.

Additionally, Fab' fragments can be directly recovered from E. coli and chemically coupled to form bispecific antibodies. Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized bispecific antibody F(ab')₂ molecule. Each Fab' fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets.

Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148(5):1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab' portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The "diabody" technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (V_L) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the VH and V domains of one fragment are forced to pair with the complementary V and V_H domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al, J. Immunol. 152:5368 (1994).

Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

Exemplary bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention. Alternatively, an anti-antigenic arm of an immunoglobulin molecule can be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD 16) so as to focus cellular defense mechanisms to the cell expressing the particular antigen. Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen. These antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody of interest binds the protein antigen described herein and further binds tissue factor (TF).

Heteroconjugate Antibodies

Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Patent No. 4,676,980), and for treatment of HIV infection (WO 91/00360; WO 92/200373; EP 03089). It is contemplated that the antibodies can be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins can be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this puφose include iminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, for example, in U.S. Patent No. 4,676,980. Effector Function Engineering

It can be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residue(s) can be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated can have improved intemalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al., J. Exp Med., 176: 1191-1195 (1992) and Shopes, J. Immunol., 148: 2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity can also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research, 53: 2560-2565 (1993). Alternatively, an antibody can be engineered that has dual Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3: 219-230 (1989).

Immunoconjugates

The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate).

Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include ²¹²Bi, ¹³¹1, ¹³¹In, ⁹⁰Y, and ¹⁸⁶Re.

Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as l,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al., Science, 238: 1098 (1987). Carbon- 14-labeled l-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See WO94/11026.

In another embodiment, the antibody can be conjugated to a "receptor" (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a "ligand" (e.g., avidin) that is in turn conjugated to a cytotoxic agent.

Immunoliposomes

The antibodies disclosed herein can also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Patent No. 5,013,556.

Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab' fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al .,_J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. See Gabizon et al, J. National Cancer Inst, 81(19): 1484 (1989).

Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention

In one embodiment, methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme linked immunosorbent assay (ELISA) and other immunologically mediated techniques known within the art. In a specific embodiment, selection of antibodies that are specific to a particular domain of an NOVX protein is facilitated by generation of hybridomas that bind to the fragment of an NOVX protein possessing such a domain. Thus, antibodies that are specific for a desired domain within an NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

Antibodies directed against a NOVX protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of a NOVX protein (e.g., for use in measuring levels of the NOVX protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies specific to a NOVX protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain, are utilized as pharmacologically active compounds (referred to hereinafter as "Therapeutics").

An antibody specific for a NOVX protein of the invention (e.g., a monoclonal antibody or a polyclonal antibody) can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells. Moreover, such an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein. Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include ¹²⁵I, ¹³¹I, ³⁵S or ³H.

Antibody Therapeutics

Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject. An antibody preparation, preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds. In this case, the antibody binds to the target and masks a binding site of the naturally occurring ligand, wherein the ligand serves as an effector molecule. Thus the receptor mediates a signal transduction pathway for which ligand is responsible.

Alternatively, the effect may be one in which the antibody elicits a physiological result by virtue of binding to an effector binding site on the target molecule. In this case the target, a receptor having an endogenous ligand which may be absent or defective in the disease or pathology, binds the antibody as a surrogate effector ligand, initiating a receptor-based signal transduction event by the receptor.

A therapeutically effective amount of an antibody of the invention relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target, and in other cases, promotes a physiological response. The amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered. Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the invention may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg/kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.

Pharmaceutical Compositions of Antibodies

Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington : The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa. : 1995; Dmg Absoφtion Enhancement : Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Dmg Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.

If the antigenic protein is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7893 (1993). The formulation herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition can comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the puφose intended.

The active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal dmg delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.

The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

Sustained-release preparations can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT ™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.

ELISA Assay

An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., F_ab or F(_ab)₂) can be used. The term "labeled", with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fiuorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fiuorescently-labeled streptavidin. The term "biological sample" is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term "biological sample", therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in "ELISA: Theory and Practice: Methods in Molecular Biology", Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, NJ, 1995; "Immunoassay", E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, CA, 1996; and "Practice and Theory of Enzyme Immunoassays", P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques. NOVX Recombinant Expression Vectors and Host Cells

Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding a NOVX protein, or derivatives, fragments, analogs or homologs thereof. As used herein, the term "vector" refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid", which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g. , non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are referred to herein as "expression vectors". In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. In the present specification, "plasmid" and "vector" can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retrovimses, adenoviruses and adeno-associated viruses), which serve equivalent functions.

The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, "operably-linked" is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).

The term "regulatory sequence" is intended to includes promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., NOVX proteins, mutant forms of NOVX proteins, fusion proteins, etc.).

The recombinant expression vectors of the invention can be designed for expression of NOVX proteins in prokaryotic or eukaryotic cells. For example, NOVX proteins can be expressed in bacterial cells such as Escherichia coli, insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.

Expression of proteins in prokaryotes is most often carried out in Escherichia coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three puφoses: (ϊ) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988. Gene 67: 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, NJ.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.

Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al, (1988) Gene 69:301-315) and pET lid (Studier et al, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89). One strategy to maximize recombinant protein expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See, e.g., Gottesman, GΕNΕ EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in E. coli (see, e.g., Wada, et al, 1992. Nucl Acids Res. 20: 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.

In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSecl (Baldari, etal, 1987. EMBOJ. 6: 229-234), pMFa (Kurjan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al, 1987. Gene 54: 113-123), pYES2 (Invitrogen Coφoration, San Diego, Calif), and picZ (InVitrogen Coφ, San Diego, Calif).

Alternatively, NOVX can be expressed in insect cells using baculovirus expression vectors. Baculovims vectors available for expression of proteins in cultured insect cells (e.g., SF9 cells) include the pAc series (Smith, etal, 1983. Mol. Cell. Biol. 3: 2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology 170: 31-39).

In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDMS (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al, 1987. EMBO J. 6: 187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, adenovims 2, cytomegalovirus, and simian vims 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al, MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y., 1989.

In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al, 1987. Genes Dev. 1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol. 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins (Banerji, et al, 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et l, 1985. Science 230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Grass, 1990. Science 249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).

The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively-linked to a regulatory sequence in a manner that allows for expression (by transcription of the DNA molecule) of an RNA molecule that is antisense to NOVX mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen that direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen that direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated vims in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see, e.g., Weintraύb, et al, "Antisense RNA as a molecular tool for genetic analysis," Reviews-Trends in Genetics, Vol. 1(1) 1986.

Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms "host cell" and "recombinant host cell" are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but also to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.

A host cell can be any prokaryotic or eukaryotic cell. For example, NOVX protein can be expressed in bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art. Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms "transformation" and "transfection" are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.

For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e.g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Various selectable markers include those that confer resistance to drags, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding NOVX or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drag selection (e.g., cells that have incoφorated the selectable marker gene will survive, while the other cells die).

A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) NOVX protein. Accordingly, the invention further provides methods for producing NOVX protein using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding NOVX protein has been introduced) in a suitable medium such that NOVX protein is produced. In another embodiment, the method further comprises isolating NOVX protein from the medium or the host cell.

Transgenic NOVX Animals

The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which NOVX protein-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in wliich exogenous NOVX sequences have been introduced into their genome or homologous recombinant animals in which endogenous NONX sequences have been altered. Such animals are useful for studying the function and/or activity of ΝONX protein and for identifying and/or evaluating modulators of NONX protein activity. As used herein, a "transgenic animal" is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, etc. A transgene is exogenous DΝA that is integrated into the genome of a cell from which a transgenic animal develops and that remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a "homologous recombinant animal" is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous ΝOVX gene has been altered by homologous recombination between the endogenous gene and an exogenous DΝA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal.

A transgenic animal of the invention can be created by introducing ΝOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retro viral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human ΝOVX cDΝA sequences, i.e., any one of SEQ ID ΝO:2«-l, wherein n is an integer between 1 and 174, can be introduced as a transgene into the genome of a non-human animal. Alternatively, a non-human homologue of the human NOVX gene, such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Patent Nos. 4,736,866; 4,870,009; and 4,873,191; and Hogan, 1986. In: MANIPULATING THE MOUSE EMBRYO, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the NOVX transgene in its genome and/or expression of NOVX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene-encoding NOVX protein can further be bred to other transgenic animals carrying other transgenes. To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g. , functionally disrupt, the NOVX gene. The NOVX gene can be a human gene (e.g., the cDNA of any one of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174), but more preferably, is a non-human homologue of a human NOVX gene. For example, a mouse homologue of human NOVX gene of SEQ ID NO:2rc-l, wherein n is an integer between 1 and 174, can be used to constmct a homologous recombination vector suitable for altering an endogenous NOVX gene in the mouse genome. In one embodiment, the vector is designed such that, upon homologous recombination, the endogenous NOVX gene is functionally dismpted (i.e., no longer encodes a functional protein; also referred to as a "knock out" vector).

Alternatively, the vector can be designed such that, upon homologous recombination, the endogenous NOVX gene is mutated or otherwise altered but still encodes functional protein (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous NOVX protein). In the homologous recombination vector, the altered portion of the NOVX gene is flanked at its 5'- and 3'-termini by additional nucleic acid of the NOVX gene to allow for homologous recombination to occur between the exogenous NOVX gene carried by the vector and an endogenous NOVX gene in an embryonic stem cell. The additional flanking NOVX nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5'- and 3'-termini) are included in the vector. See, e.g., Thomas, et al, 1987. Cell 51 : 503 for a description of homologous recombination vectors. The vector is ten introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced NOVX gene has homologously-recombined with the endogenous NOVX gene are selected. See, e.g., Li, et al, 1992. Cell 69: 915.

The selected cells are then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras. See, e.g., Bradley, 1987. In: TERATOCARCINOMAS AND EMBRYONIC STEM CELLS: A PRACTICAL APPROACH, Robertson, ed. IRL, Oxford, pp. 113-152. A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously-recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously-recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination vectors and homologous recombinant animals are described further in Bradley, 1991. Curr. Opin. Biotechnol. 2: 823-829; PCT International Publication Nos.: WO 90/11354; WO 91/01140; WO 92/0968; and WO 93/04169.

In another embodiment, transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage PI. For a description of the cre/loxP recombinase system, See, e.g., Lakso, et al, 1992. Proc. Natl. Acad. Sci. USA 89: 6232-6236. Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae. See, O'Gorman, et al, 1991. Science 251:1351-1355. If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of "double" transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.

Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al, 1997. Nature 385: 810-813. In brief, a cell (e.g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter Go phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g., the somatic cell) is isolated.

Pharmaceutical Compositions

The NOVX nucleic acid molecules, NOVX proteins, and anti-NOVX antibodies (also referred to herein as "active compounds") of the invention, and derivatives, fragments, analogs and homologs thereof, can be incoφorated into pharmaceutical compositions suitable for administration. Such compositions typically comprise the nucleic acid molecule, protein, or antibody and a pharmaceutically acceptable carrier. As used herein, "pharmaceutically acceptable carrier" is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absoφtion delaying agents, and the like, compatible with pharmaceutical administration. Suitable carriers are described in the most recent edition of Remington's Pharmaceutical Sciences, a standard reference text in the field, which is incoφorated herein by reference. Preferred examples of such carriers or diluents include, but are not limited to, water, saline, finger's solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incoφorated into the compositions.

A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.

Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL (BASF, Parsippany, NJ.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absoφtion of the injectable compositions can be brought about by including in the composition an agent which delays absoφtion, for example, aluminum monostearate and gelatin.

Sterile injectable solutions can be prepared by incoφorating the active compound (e.g., a NOVX protein or anti-NOVX antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incoφorating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the puφose of oral therapeutic administration, the active compound can be incoφorated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer.

Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.

The compounds can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.

In one embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Coφoration and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Patent No. 4,522,811.

It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals.

The nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e.g., U.S. Patent No. 5,328,470) or by stereotactic injection (see, e.g., Chen, et al, 1994. Proc. Natl. Acad. Sci. USA 91: 3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retro viral vectors, the pharmaceutical preparation can include one or more cells that produce the gene delivery system. The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

Screening and Detection Methods

The isolated nucleic acid molecules of the invention can be used to express NOVX protein (e.g., via a recombinant expression vector in a host cell in gene therapy applications), to detect NOVX mRNA (e.g., in a biological sample) or a genetic lesion in a NOVX gene, and to modulate NOVX activity, as described further, below. In addition, the NOVX proteins can be used to screen drugs or compounds that modulate the NOVX protein activity or expression as well as to treat disorders characterized by insufficient or excessive production of NOVX protein or production of NOVX protein forms that have decreased or aberrant activity compared to NOVX wild-type protein (e.g.; diabetes (regulates insulin release); obesity (binds and transport lipids); metabolic disturbances associated with obesity, the metabolic syndrome X as well as anorexia and wasting disorders associated with chronic diseases and various cancers, and infectious disease(possesses anti-microbial activity) and the various dyshpidemias. In addition, the anti-NOVX antibodies of the invention can be used to detect and isolate NOVX proteins and modulate NOVX activity. In yet a further aspect, the invention can be used in methods to influence appetite, absoφtion of nutrients and the disposition of metabolic substrates in both a positive and negative fashion.

The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

Screening Assays

The invention provides a method (also referred to herein as a "screening assay") for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drags) that bind to NOVX proteins or have a stimulatory or inhibitory effect on, e.g., NOVX protein expression or NOVX protein activity. The invention also includes compounds identified in the screening assays described herein.

In one embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of the membrane-bound form of a NOVX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the "one-bead one-compound" library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g., Lam, 199 '. Anticαncer Drug Design 12: 145.

A "small molecule" as used herein, is meant to refer to a composition that has a molecular weight of less than about 5 kD and most preferably less than about 4 kD. Small molecules can be, e.g., nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic molecules. Libraries of chemical and/or biological mixtures, such as fungal, bacterial, or algal extracts, are known in the art and can be screened with any of the assays of the invention.

Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt, et αl., 1993. Proc. Nαtl. Acαd. Sci. U.S.A. 90: 6909; Erb, et αl, 1994. Proc. Nαtl. Acαd. Sci. U.S.A. 91: 11422; Zuckermann, et αl, 1994. J. Med. Chem. 37: 2678; Cho, et αl, 1993. Science 261: 1303; Carrell, et αl, l994. Angew. Chem. Int. Ed. Engl. 33: 2059; Carell, et αl, 1994. Angew. Chem. Int. Ed. Engl. 33: 2061; and Gallop, et αl., 1994. J. Med. Chem. 37: 1233.

Libraries of compounds may be presented in solution (e.g., Houghten, 1992. Biotechniques 13: 412-421), or on beads (Lam, 1991. Nature 354: 82-84), on chips (Fodor, 1993. Nature 364: 555-556), bacteria (Ladner, U.S. Patent No. 5,223,409), spores (Ladner, U.S. Patent 5,233,409), plasmids (Cull, et al, 1992. Proc. Natl. Acad. Sci. USA 89: 1865-1869) or on phage (Scott and Smith, 1990. Science 249: 386-390; Devlin, 1990. Science 249: 404-406; Cwirla, et al, 1990. Proc. Natl. Acad. Sci. U.S.A. 87: 6378-6382; Felici, 1991. J. Mol. Biol. 222: 301-310; Ladner, U.S. Patent No. 5,233,409.).

In one embodiment, an assay is a cell-based assay in which a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to a NOVX protein determined. The cell, for example, can of mammalian origin or a yeast cell. Determining the ability of the test compound to bind to the NOVX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the NOVX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex. For example, test compounds can be labeled with ¹²⁵1, ³⁵S, ¹⁴C, or ³H, either directly or indirectly, and the radioisotope detected by direct counting of radioemission or by scintillation counting. Alternatively, test compounds can be enzymatically-labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product. In one embodiment, the assay comprises contacting a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX protein or a biologically-active portion thereof as compared to the known compound.

In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX or a biologically-active portion thereof can be accomplished, for example, by determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule. As used herein, a "target molecule" is a molecule with which a NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses a NOVX interacting protein, a molecule on the surface of a second cell, a molecule in the extracellular milieu, a molecule associated with the internal surface of a cell membrane or a cytoplasmic molecule. A NOVX target molecule can be a non-NOVX molecule or a NOVX protein or polypeptide of the invention. In one embodiment, a NOVX target molecule is a component of a signal transduction pathway that facilitates transduction of an extracellular signal (e.g. a signal generated by binding of a compound to a membrane-bound NOVX molecule) through the cell membrane and into the cell. The target, for example, can be a second intercellular protein that has catalytic activity or a protein that facilitates the association of downstream signaling molecules with NOVX.

Determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e. intracellular Ca²⁺, diacylglycerol, IP₃, etc.), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising a NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.

In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting a NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the NOVX protein or biologically-active portion thereof. Binding of the test compound to the NOVX protein can be determined either directly or indirectly as described above. In one such embodiment, the assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX or biologically-active portion thereof as compared to the known compound.

In still another embodiment, an assay is a cell-free assay comprising contacting NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to modulate (e.g. stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX can be accomplished, for example, by determining the ability of the NOVX protein to bind to a NOVX target molecule by one of the methods described above for determining direct binding. In an alternative embodiment, determining the ability of the test compound to modulate the activity of NOVX protein can be accomplished by determining the ability of the NOVX protein further modulate a NOVX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.

In yet another embodiment, the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of a NOVX target molecule.

The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton^® X-100, Triton^® X-l 14, Thesit^®, Isotridecypoly(ethylene glycol ether)_n, N-dodecyl~N,N-dimethyl-3-ammonio-l -propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1 -propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-l-propane sulfonate (CHAPSO).

In more than one embodiment of the above assay methods of the invention, it may be desirable to immobilize either NOVX protein or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to NOVX protein, or interaction of NOVX protein with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided that adds a domain that allows one or both of the proteins to be bound to a matrix. For example, GST-NO VX fusion proteins or GST-target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, MO) or glutathione derivatized microtiter plates, that are then combined with the test compound or the test compound and either the non-adsorbed target protein or NOVX protein, and the mixture is incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads or microtiter plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described, supra. Alternatively, the complexes can be dissociated from the matrix, and the level of NOVX protein binding or activity determined using standard techniques.

Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either the NOVX protein or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated NOVX protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques well-known within the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, 111.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with NOVX protein or target molecules, but which do not interfere with binding of the NOVX protein to its target molecule, can be derivatized to the wells of the plate, and unbound target or NOVX protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the NOVX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the NOVX protein or target molecule.

In another embodiment, modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (i.e., statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of NOVX mRNA or protein expression. Alternatively, when expression of NOVX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of NOVX mRNA or protein expression. The level of NOVX mRNA or protein expression in the cells can be determined by methods described herein for detecting NOVX mRNA or protein.

In yet another aspect of the invention, the NOVX proteins can be used as "bait proteins" in a two-hybrid assay or three hybrid assay (see, e.g. , U.S. Patent No. 5,283,317; Zervos, et al, 1993. Cell 72: 223-232; Madura, et al, 1993. J. Biol. Chem. 268: 12046-12054; Barrel, et al, 1993. Biotechniques 14: 920-924; Iwabuchi, et al, 1993. Oncogene 8: 1693-1696; and Brent WO 94/10300), to identify other proteins that bind to or interact with NOVX ("NOVX-binding proteins" or "NOVX-bp") and modulate NOVX activity. Such NOVX-binding proteins are also involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.

The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for NOVX is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g. , GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein ("prey" or "sample") is fused to a gene that codes for the activation domain of the known transcription factor. If the "bait" and the "prey" proteins are able to interact, in vivo, forming a NOVX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.

The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

Detection Assays

Portions or fragments of the cDNA sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. By way of example, and not of limitation, these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample. Some of these applications are described in the subsections, below.

Chromosome Mapping

Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174, or fragments or derivatives thereof, can be used to map the location of the NOVX genes, respectively, on a chromosome. The mapping of the NOVX sequences to chromosomes is an important first step in correlating these sequences with genes associated with disease.

Briefly, NOVX genes can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp in length) from the NOVX sequences. Computer analysis of the NOVX, sequences can be used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers can then be used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to the NOVX sequences will yield an amplified fragment. Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e.g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e.g., D'Eustachio, et al, 1983. Science 220: 919-924. Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.

PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular sequence to a particular chromosome. Three or more sequences can be assigned per day using a single thermal cycler. Using the NOVX sequences to design oligonucleotide primers, sub-localization can be achieved with panels of fragments from specific chromosomes.

Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal spread can further be used to provide a precise chromosomal location in one step. Chromosome spreads can be made using cells whose division has been blocked in metaphase by a chemical like colcemid that disrupts the mitotic spindle. The chromosomes can be treated briefly with trypsin, and then stained with Giemsa. A pattern of light and dark bands develops on each chromosome, so that the chromosomes can be identified individually. The FISH technique can be used with a DNA sequence as short as 500 or 600 bases. However, clones larger than 1,000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. Preferably 1,000 bases, and more preferably 2,000 bases, will suffice to get good results at a reasonable amount of time. For a review of this technique, see, Verma, et al, HUMAN CHROMOSOMES: A MANUAL OF BASIC TECHNIQUES (Pergamon Press, New York 1988).

Reagents for chromosome mapping can be used individually to mark a single chromosome or a single site on that chromosome, or panels of reagents can be used for marking multiple sites and/or multiple chromosomes. Reagents corresponding to noncoding regions of the genes actually are preferred for mapping puφoses. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping. Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found, e.g., in McKusick, MENDELIAN INHERITANCE IN MAN, available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, e.g., Egeland, et al, 1987. Nature, 325: 783-787.

Moreover, differences in the DNA sequences between individuals affected and unaffected with a disease associated with the NOVX gene, can be determined. If a mutation is observed in some or all of the affected individuals but not in any unaffected individuals, then the mutation is likely to be the causative agent of the particular disease. Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that DNA sequence. Ultimately, complete sequencing of genes from several individuals can be performed to confirm the presence of a mutation and to distinguish mutations from polymoφhisms.

Tissue Typing

The NOVX sequences of the invention can also be used to identify individuals from minute biological samples. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification. The sequences of the invention are useful as additional DNA markers for RFLP ("restriction fragment length polymoφhisms," described in U.S. Patent No. 5,272,057).

Furthermore, the sequences of the invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual's genome. Thus, the NOVX sequences described herein can be used to prepare two PCR primers from the 5'- and 3'-termini of the sequences. These primers can then be used to amplify an individual's DNA and subsequently sequence it.

Panels of corresponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences. The sequences of the invention can be used to obtain such identification sequences from individuals and from tissue. The NOVX sequences of the invention uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Much of the allelic variation is due to single nucleotide polymoφhisms (SNPs), which include restriction fragment length polymoφhisms (RFLPs).

Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification puφoses. Because greater numbers of polymoφhisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If coding sequences, such as those of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

Predictive Medicine

The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) puφoses to thereby treat an individual prophylactically. Accordingly, one aspect of the invention relates to diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant NOVX expression or activity. The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, and hematopoietic disorders, and the various dyshpidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in a NOVX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive puφose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity.

Another aspect of the invention provides methods for determining NOVX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (referred to herein as "pharmacogenomics"). Pharmacogenomics allows for the selection of agents (e.g., drags) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e.g., the genotype of the individual examined to determine the ability of the individual to respond to a particular agent.)

Yet another aspect of the invention pertains to monitoring the influence of agents (e.g., drags, compounds) on the expression or activity of NOVX in clinical trials.

These and other agents are described in further detail in the following sections.

Diagnostic Assays

An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample. An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO:2«-l, wherein n is an integer between 1 and 174, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to NOVX mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays of the invention are described herein.

An agent for detecting NOVX protein is an antibody capable of binding to NOVX protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab')₂) can be used. The term "labeled", with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fiuorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fiuorescently-labeled streptavidin. The term "biological sample" is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of NOVX genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of NOVX protein include introducing into a subject a labeled anti-NOVX antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

In one embodiment, the biological sample contains protein molecules from the test subject. Alternatively, the biological sample can contain mRNA molecules from the test subject or genomic DNA molecules from the test subject. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject.

In another embodiment, the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting NOVX protein, mRNA, or genomic DNA, such that the presence of NOVX protein, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of NOVX protein, mRNA or genomic DNA in the control sample with the presence of NOVX protein, mRNA or genomic DNA in the test sample.

The invention also encompasses kits for detecting the presence of NOVX in a biological sample. For example, the kit can comprise: a labeled compound or agent capable of detecting NOVX protein or mRNA in a biological sample; means for determining the amount of NOVX in the sample; and means for comparing the amount of NOVX in the sample with a standard. The compound or agent can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect NOVX protein or nucleic acid.

Prognostic Assays

The diagnostic methods described herein can furthermore be utilized to identify subjects having or at risk of developing a disease or disorder associated with aberrant NOVX expression or activity. For example, the assays described herein, such as the preceding diagnostic assays or the following assays, can be utilized to identify a subject having or at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. Alternatively, the prognostic assays can be utilized to identify a subject having or at risk for developing a disease or disorder. Thus, the invention provides a method for identifying a disease or disorder associated with aberrant NOVX expression or activity in which a test sample is obtained from a subject and NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) is detected, wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject having or at risk of developing a disease or disorder associated with aberrant NOVX expression or activity. As used herein, a "test sample" refers to a biological sample obtained from a subject of interest. For example, a test sample can be a biological fluid (e.g., serum), cell sample, or tissue.

Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) to treat a disease or disorder associated with aberrant NOVX expression or activity. For example, such methods can be used to determine whether a subject can be effectively treated with an agent for a disorder. Thus, the invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with aberrant NOVX expression or activity in which a test sample is obtained and NOVX protein or nucleic acid is detected (e.g., wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject that can be administered the agent to treat a disorder associated with aberrant NOVX expression or activity).

The methods of the invention can also be used to detect genetic lesions in a NOVX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by aberrant cell proliferation and/or differentiation. In various embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding a NOVX-protein, or the misexpression of the NOVX gene. For example, such genetic lesions can be detected by ascertaining the existence of at least one of: (i) a deletion of one or more nucleotides from a NOVX gene; (ii) an addition of one or more nucleotides to a NOVX gene; (iii) a substitution of one or more nucleotides of a NOVX gene, (iv) a chromosomal rearrangement of a NOVX gene; (v) an alteration in the level of a messenger RNA transcript of a NOVX gene, (vi) aberrant modification of a NOVX gene, such as of the methylation pattern of the genomic DNA, (vii) the presence of a non- wild-type splicing pattern of a messenger RNA transcript of a NOVX gene, (viii) a non- wild-type level of a NOVX protein, (ix) allelic loss of a NOVX gene, and (x) inappropriate post-translational modification of a NOVX protein. As described herein, there are a large number of assay techniques known in the art which can be used for detecting lesions in a NOVX gene. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.

In certain embodiments, detection of the lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Patent Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran, et al, 1988. Science 241: 1077-1080; andNakazawa, et al, 1994. Proc. Natl. Acad. Sci. USA 91 : 360-364), the latter of which can be particularly useful for detecting point mutations in the NOVX-gene (see, Abravaya, et al, 1995. Nucl. Acids Res. 23: 675-682). This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers that specifically hybridize to a NOVX gene under conditions such that hybridization and amplification of the NOVX gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any of the techniques used for detecting mutations described herein.

Alternative amplification methods include: self sustained sequence replication (see, Guatelli, etal, 1990. Proc. Natl. Acad. Sci. USA 87: 1874-1878), transcriptional amplification system (see, Kwoh, etal, 1989. Proc. Natl. Acad, Sci. USA 86: 1173-1177); Qβ Replicase (see, Lizardi, et al, 1988. BioTechnology 6: 1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.

In an alternative embodiment, mutations in a NOVX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, e.g., U.S. Patent No. 5,493,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.

In other embodiments, genetic mutations in NOVX can be identified by hybridizing a sample and control nucleic acids, e.g., DNA or RNA, to high-density arrays containing hundreds or thousands of oligonucleotides probes. See, e.g., Cronin, et al, 1996. Human Mutation 1: 244-255; Kozal, et al, 1996. Nat. Med. 2: 753-759. For example, genetic mutations in NOVX can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin, et al, supra. Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA in a sample and control to identify base changes between the sequences by making linear arrays of sequential overlapping probes. This step allows the identification of point mutations. This is followed by a second hybridization array that allows the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants or mutations detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.

In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the NOVX gene and detect mutations by comparing the sequence of the sample NOVX with the corresponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxim and Gilbert, 1977. Proc. Natl. Acad. Sci. USA 74: 560 or Sanger, 1977. Proc. Natl. Acad. Sci. USA 74: 5463. It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (see, e.g., Naeve, et al, 1995. Biotechniques 19: 448), including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94/16101; Cohen, et l, 1996. Adv. Chromatography 36: 127-162; and Griffin, et al, 1993. Appl. Biochem. Biotechnol. 38: 147-159).

Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA DNA heteroduplexes. See, e.g., Myers, et al, 1985. Science 230: 1242. In general, the art technique of "mismatch cleavage" starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S_t nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al, 1988. Proc. Natl. Acad. Sci. USA 85: 4397; Saleeba, et al, 1992. Methods Enzymol. 217: 286-295. In an embodiment, the control DNA or RNA can be labeled for detection.

In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called "DNA mismatch repair" enzymes) in defined systems for detecting and mapping point mutations in NOVX cDNAs obtained from samples of cells. For example, the mutY enzyme of E. coli cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. See, e.g., Hsu, et al, 1994. Car cinogenesis 15: 1657-1662. According to an exemplary embodiment, a probe based on a NOVX sequence, e.g. , a wild-type NOVX sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e.g., U.S. Patent No. 5,459,039.

In other embodiments, alterations in electrophoretic mobility will be used to identify mutations in NOVX genes. For example, single strand conformation polymoφhism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids. See, e.g., Orita, et al, 1989. Proc. Natl. Acad. Sci. USA: 86: 2766; Cotton, 1993. Mutat. Res. 285: 125-144; Hayashi, 1992. Genet. Anal. Tech. Appl. 9: 73-79. Single-stranded DNA fragments of sample and control NOVX nucleic acids will be denatured and allowed to renature. The secondary stmcture of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In one embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility. See, e.g., Keen, et al, 1991. Trends Genet. 7: 5.

In yet another embodiment, the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGΕ). See, e.g., Myers, et al, 1985. Nature 313: 495. When DGGΕ is used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA. See, e.g., Rosenbaum and Reissner, 1987 ^'. Biophys. Chem. 265: 12753. Examples of other techniques for detecting point mutations include, but are not limited to, selective oligonucleotide hybridization, selective amplification, or selective primer extension. For example, oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions that permit hybridization only if a perfect match is found. See, e.g., Saiki, etal, 1986. Nature 324: 163; Saiki, et al, 1989. Proc. Natl. Acad. Sci. USA 86: 6230. Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.

Alternatively, allele specific amplification technology that depends on selective PCR amplification may be used in conjunction with the instant invention. Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization; see, e.g., Gibbs, et al, 1989. Nucl. Acids Res. 17: 2437-2448) or at the extreme 3'-terminus of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (see, e.g., Prossner, 1993. Tibtech. 11: 238). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection. See, e.g., Gasparini, et al, 1992. Mol. Cell Probes 6: . It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification. See, e.g., Barany, 991. Proc. Natl. Acad. Sci. USA 88: 189. In such cases, ligation will occur only if there is a perfect match at the 3 '-terminus of the 5' sequence, making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification.

The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e.g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving a NOVX gene.

Furthermore, any cell type or tissue, preferably peripheral blood leukocytes, in which NOVX is expressed may be utilized in the prognostic assays described herein. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.

Pharmacogenomics

Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

In conjunction with such treatment, the pharmacogenomics (i.e., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drag) of the individual may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drag. Thus, the pharmacogenomics of the individual permits the selection of effective agents (e.g., drags) for prophylactic or therapeutic treatments based on a consideration of the individual's genotype. Such pharmacogenomics can further be used to determine appropriate dosages and therapeutic regimens. Accordingly, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual.

Pharmacogenomics deals with clinically significant hereditary variations in the response to drags due to altered drug disposition and abnormal action in affected persons. See e.g., Eichelbaum, 1996. Clin. Exp. Pharmacol. Physiol., 23: 983-985; Linder, 1997. Clin. Chem., 43: 254-266. In general, two types of pharmacogenetic conditions can be differentiated. Genetic conditions transmitted as a single factor altering the way drugs act on the body (altered drag action) or genetic conditions transmitted as single factors altering the way the body acts on drugs (altered drug metabolism). These pharmacogenetic conditions can occur either as rare defects or as polymoφhisms. For example, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymopathy in which the main clinical complication is hemolysis after ingestion of oxidant drags (anti-malarials, sulfonamides, analgesics, nitrofurans) and consumption of fava beans.

As an illustrative embodiment, the activity of drag metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymoφhisms of drag metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome pregnancy zone protein precursor enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drag response and serious toxicity after taking the standard and safe dose of a drag. These polymoφhisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymoφhic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its C YP2D6-formed metabolite moφbine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.

Thus, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual. In addition, pharmacogenetic studies can be used to apply genotyping of polymoφhic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug responsiveness phenotype. This knowledge, when applied to dosing or drag selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with a NOVX modulator, such as a modulator identified by one of the exemplary screening assays described herein.

Monitoring of Effects During Clinical Trials

Monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX (e.g., the ability to modulate aberrant cell proliferation and/or differentiation) can be applied not only in basic drug screening, but also in clinical trials. For example, the effectiveness of an agent determined by a screening assay as described herein to increase NONX gene expression, protein levels, or upregulate ΝONX activity, can be monitored in clinical trails of subjects exhibiting decreased ΝONX gene expression, protein levels, or downregulated ΝONX activity. Alternatively, the effectiveness of an agent determined by a screening assay to decrease ΝONX gene expression, protein levels, or downregulate ΝONX activity, can be monitored in clinical trails of subjects exhibiting increased ΝONX gene expression, protein levels, or upregulated ΝONX activity. In such clinical trials, the expression or activity of ΝOVX and, preferably, other genes that have been implicated in, for example, a cellular proliferation or immune disorder can be used as a "read out" or markers of the immune responsiveness of a particular cell.

By way of example, and not of limitation, genes, including ΝOVX, that are modulated in cells by treatment with an agent (e.g., compound, drag or small molecule) that modulates NOVX activity (e.g., identified in a screening assay as described herein) can be identified. Thus, to study the effect of agents on cellular proliferation disorders, for example, in a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of NOVX and other genes implicated in the disorder. The levels of gene expression (i.e., a gene expression pattern) can be quantified by Northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of protein produced, by one of the methods as described herein, or by measuring the levels of activity of NOVX or other genes. In this manner, the gene expression pattern can serve as a marker, indicative of the physiological response of the cells to the agent. Accordingly, this response state may be determined before, and at various points during, treatment of the individual with the agent.

In one embodiment, the invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, protein, peptide, peptidomimetic, nucleic acid, small molecule, or other drag candidate identified by the screening assays described herein) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent; (ii) detecting the level of expression of a NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i.e., to decrease the effectiveness of the agent.

Methods of Treatment

The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant NOVX expression or activity. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

These methods of treatment will be discussed more fully, below. Diseases and Disorders

Diseases and disorders that are characterized by increased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that antagonize (i.e., reduce or inhibit) activity. Therapeutics that antagonize activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to: (i) an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; (ii) antibodies to an aforementioned peptide; (iii) nucleic acids encoding an aforementioned peptide; (iv) administration of antisense nucleic acid and nucleic acids that are "dysfunctional" (i.e., due to a heterologous insertion within the coding sequences of coding sequences to an aforementioned peptide) that are utilized to "knockout" endogenous function of an aforementioned peptide by homologous recombination (see, e.g., Capecchi, 1989. Science 244: 1288-1292); or (v) modulators ( i.e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide of the invention) that alter the interaction between an aforementioned peptide and its binding partner.

Diseases and disorders that are characterized by decreased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that increase (i.e., are agonists to) activity. Therapeutics that upregulate activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to, an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; or an agonist that increases bioavailability.

Increased or decreased levels can be readily detected by quantifying peptide and/or RNA, by obtaining a patient tissue sample (e.g., from biopsy tissue) and assaying it in vitro for RNA or peptide levels, structure and/or activity of the expressed peptides (or mRNAs of an aforementioned peptide). Methods that are well-known within the art include, but are not limited to, immunoassays (e.g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc.) and/or hybridization assays to detect expression of mRNAs (e.g., Northern assays, dot blots, in situ hybridization, and the like).

Prophylactic Methods

In one aspect, the invention provides a method for preventing, in a subject, a disease or condition associated with an aberrant NOVX expression or activity, by administering to the subject an agent that modulates NOVX expression or at least one NOVX activity. Subjects at risk for a disease that is caused or contributed to by aberrant NOVX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of the NOVX aberrancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending upon the type of NOVX aberrancy, for example, a NOVX agonist or NOVX antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein. The prophylactic methods of the invention are further discussed in the following subsections.

Therapeutic Methods

Another aspect of the invention pertains to methods of modulating NOVX expression or activity for therapeutic puφoses. The modulatory method of the invention involves contacting a cell with an agent that modulates one or more of the activities of NOVX protein activity associated with the cell. An agent that modulates NOVX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of a NOVX protein, a peptide, a NOVX peptidomimetic, or other small molecule. In one embodiment, the agent stimulates one or more NOVX protein activity. Examples of such stimulatory agents include active NOVX protein and a nucleic acid molecule encoding NOVX that has been introduced into the cell. In another embodiment, the agent inhibits one or more NOVX protein activity. Examples of such inhibitory agents include antisense NOVX nucleic acid molecules and anti-NOVX antibodies. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject). As such, the invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant expression or activity of a NOVX protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., up-regulates or down-regulates) NOVX expression or activity. In another embodiment, the method involves administering a NONX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant ΝONX expression or activity.

Stimulation of ΝONX activity is desirable in situations in which ΝOVX is abnormally downregulated and/or in which increased ΝOVX activity is likely to have a beneficial effect. One example of such a situation is where a subject has a disorder characterized by aberrant cell proliferation and/or differentiation (e.g., cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia).

Determination of the Biological Effect of the Therapeutic

In various embodiments of the invention, suitable in vitro or in vivo assays are performed to determine the effect of a specific Therapeutic and whether its administration is indicated for treatment of the affected tissue.

In various specific embodiments, in vitro assays may be performed with representative cells of the type(s) involved in the patient's disorder, to determine if a given Therapeutic exerts the desired effect upon the cell type(s). Compounds for use in therapy may be tested in suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects. Similarly, for in vivo testing, any of the animal model system known in the art may be used prior to administration to human subjects.

Prophylactic and Therapeutic Uses of the Compositions of the Invention

The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

As an example, a cDNA encoding the NOVX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from diseases, disorders, conditions and the like, including but not limited to those listed herein.

Both the novel nucleic acid encoding the NOVX protein, and the NOVX protein of the invention, or fragments thereof, may also be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. A further use could be as an anti-bacterial molecule (i.e., some peptides have been found to possess anti-bacterial properties). These materials are further useful in the generation of antibodies, which immunospecifically-bind to the novel substances of the invention for use in therapeutic or diagnostic methods.

The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. EXAMPLES

Example A: Polynucleotide and Polypeptide Sequences, and Homology Data

Example 1.

The NO VI clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1 A.

Table 1A. NOV1 Sequence Analysis

NOVla, CG103910-02 SEQ ID NO: 1 1224 bp

DNA Sequence foRF StartTATG at 1 jORF Stop: TGA at 1041

ATGCACGTGCGCTCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGGCACCCCTGTTCCT GCTGCGCTCCGCCCTGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTCATCCACCGGCGCC TCCGCAGCCAGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCG CGCCCGCACCTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGC GGTGGAGGAGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCC AGGGCCCCCCTCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTC GTCAACCTCGTGGAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGA TCTTTCCAAGATCCCAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCC GGGAACGCTTCGACAATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGG GAATCGGATCTCTTCCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGA CATCACAGCCACCAGCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGG AGACGCTGGATGGGCAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAAC AAGCAGCCCTTCATGGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGG GAGCAAACAGCGCAGCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAACG TGGCAGGTCCACTTCATCAACCCGGAAACGGTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCAATGC CATCTCCGTCCTCTACTTCGATGACAGCTCCAACGTCATCCTGAAGAAATACAGAAACATGGTGGTCC GGGCCTGTGGCTGCCACTAGCTCCTCCGAGAATTCAGACCCTTTGGGGCCAAGTTTTTCTGGATCCTC

CATTGCTCGCCTTGGCCAGGAACCAGCAGACCAACTGCCTTTTGTGAGACCTTCCCCTCCCTATCCCC

NOVla, CGI 03910-02 SEQ ID NO: 2 347 aa MW at 39545.6kD Protein Sequence

MHVRS RAAAPHS VA WAP FL RSA ADFS DNEVHSSFIHRR RSQERREMQREI SI G PHRP RPHLQGKHNSAPMFM DLY AMAVEEGGGPGGQGFSYPYKAVFSTQGPPLASLQDSHFLTDADMVMSF VNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDYIRERFDNETFRISVYQVLQEHLGR ESDLFL DSRT ASEEGWLVFDITATSNHWWNPRHNLGLQ SVETLDGQSINPKLAGLIGRHGPQN KQPFMVAFFKATEVHFRSIRSTGSKQRSQNRSKTPKNQEALRMANVAGPLHQPGNGAQAL CAHAAQC HLRPL R

NOVlb, CG103910-03 SEQ ID NO: 3 1226 bp

DNA Sequence ORF Start: ATG at 1 (ORF Stop: TGA at 976

ATGCACGTGCGCTCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGGCACCCCTGTTCCT GCTGCGCTCCGCCCTGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTCATCCACCGGCGCC TCCGCAGCCAGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCG CGCCCGCACCTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGC GGTGGAGGAGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCC AGGGCCCCCCTCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTC GTCAACCTCGTGGAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGA TCTTTCCAAGATCCCAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCC GGGAACGCTTCGACAATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGG GAATCGGATCTCTTCCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGA CATCACAGCCACCAGCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGG AGACGCTGGATGGGCAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAAC AAGCAGCCCTTCATGGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGG GAGCAAACAGCGCAGCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAACG TGGCAGGACTGGATCATCGCGCCTGAAGGCTACGCCGCCTACTACTGTGAGGGGGAGTGTGCCTTCCC TCTGAACTCCTACATGAACGCCACCAACCACGCCATCGTGCAGACGCTGGTCCACTTCATCAACCCGG

AAACGGTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCTATGCCATCTCCGTCCTCTACTTCGATGAC

AGTTCCAACGTCATCCTGAAGAAATACAGATACATGGTGGTCCGGGCCTGTGGCTGCCACTAGCTCCT

CC

NOVlb, CG103910-03 SEQ ID NO: 4 325 aa MW at 37269.9kD Protein Sequence

MHVRSLRAAAPHSFVAL AP F LRSA ADFSLDNEVHSSFIHRR RSQERREMQREILSILG PHRP RPHLQGKHNSAPMFMLD YNAMAVEEGGGPGGQGFSYPYKAVFSTQGPP ASLQDSHFLTDADMVMSF V VEHDKEFFHPRYHHREFRFD SKIPEGEAVTAAEFRIYKDYIRERFDNETFRISVYQV QEHLGR ESD FLLDSRTL ASEEG LVFDITATSNH VVNPRHNLGLQ SVETLDGQSINPKIiAGLIGRHGPQN KQPFMVAFFKATEVHFRSIRSTGSKQRSQNRSKTPKNQEA RMANVAGLDHRA

NOVlc, CG103910-01 SEQ ID NO: 5 1878 bp DNA Sequence ORF Start: ATG at 123 ORF Stop: TAG at 1418

GGGCGCAGCGGGGCCCGTCTGCAGCAAGTGACCGACGGCCGGGACGGCCGCCTGCCCCCTCTGCCACC

TGGGGCGGTGCGGGCCCGGAGCCCGGAGCCCGGGTAGCGCGTAGAGCCGGCGCGATGCACGTGCGCTC

ACTGCGAGCTGCGGCGCCGCACAGGTTCGTGGCGCTCTGGGCACCCCTGTTCCTGCTGCGCTCCGCCC TGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTCATCCACCGGCGCCTCCGCAGCCAGGAG CGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCGCGCCCGCACCTCCA GGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGCGGTGGAGGAGGGCG GCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCCAGGGCCCCCCTCTG GCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTCGTCAACCTCGTGGA ACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGATCTTTCCAAGATCC CAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCCGGGAACGCTTCGAC AATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGGGAATCGGATCTCTT CCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGACATCACAGCCACCA GCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGGAGACGCTGGATGGG CAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAACAAGCAGCCCTTCAT GGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGGGAGCAAACAGCGCA GCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAACGTGGCAGAGAACAGC AGCAGCGACCAGAGGCAGGCCTGTAAGAAGCACGAGCTGTATGTCAGCTTCCGAGACCTGGGCTGGCA GGACTGGATCATCGCGCCTGAAGGCTACGCCGCCTACTACTGTGAGGGGGAGTGTGCCTTCCCTCTGA iACTCCTACATGAACGCCACCAACCACGCCATCGTGCAGACGCTGGTCCACTTCATCAACCCGGAAACG GTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCAATGCCATCTCCGTCCTCTACTTCGATGACAGCTC CAACGTCATCCTGAAGAAATACAGAAACATGGTGGTCCGGGCCTGTGGCTGCCACTAGCTCCTCCGAG AATTCAGACCCTTTGGGGCCAAGTTTTTCTGGATCCTCCATTGCTCGCCTTGGCCAGGAACCAGCAGA

CCAACTGCCTTTTGTGAGACCTTCCCCTCCCTATCCCCAACTTTAAAGGTGTGAGAGTATTAGGAAAC lATGAGCAGCATATGGCTTTTGATCAGTTTTTCAGTGGCAGCATCCAATGAACAAGATCCTACAAGCTG

TGCAGGCAAAACCTAGCAGGAAAAAAAAACAACGCATAAAGAAAAATGGCCGGGCCAGGTCATTGGCT

GGGAAGTCTCAGCCATGCACGGACTCGTTTCCAGAGGTAATTATGAGCGCCTACCAGCCAGGCCACCC

AGCCGTGGGAGGAAGGGGGCGTGGCAAGGGGTGGGCACATTGGTGTCTGTGCGAAAGGAAAATTGACC

CGGAAGTTCCTGTAATAAATGTCACAATAAAACGAATGAATG

NOVlc, CG103910-01 SEQ ID NO: 6 431 aa MW at 49312.4kD Protein Sequence

MHVRSLRAAAPHSFVA APLF LRSALADFSLDNEVHSSFIHRRLRSQERREMQREI SI G PHRP RPHLQG HNSAPMF LDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPP AS QDSHFLTDADMVMSF VNLVEHDKEFFHPRYHHRΞFRFD SKIPEGEAVTAAEFRIY DYIRERFDNETFRISVYQVLQEH GR ESD F LDSRT ASEEGW VFDITATS HWWNPRHNLGLQLSVET DGQSINP AGLIGRHGPQN QPFMVAFFKATEVHFRSIRSTGS QRSQNRSKTPKNQEA RMANVAENSSSDQRQACKKHE YVSFR DLGWQD IIAPEGYAAYYCEGECAFPLNSYMNATNHAIVQTLVHFINPETVPKPCCAPTQLNAISV Y FDDSSNVI KKYR WRACGCH

NOVld, CG103910-04 SEQ ID NO: 7 997 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: end of sequence

CACCGGATCCACCATGCACGTGCGCTCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGG CACCCCTGTTCCTGCTGCGCTCCGCCCTGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTC ATCCACCGGCGCCTCCGCAGCCAGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTT GCCCCACCGCCCGCGCCCGCACCTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGT ACAACGCCATGGCGGTGGAGGAGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCC GTCTTCAGTACCCAGGGCCCCCCTCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACAT GGTCATGAGCTTCGTCAACCTCGTGGAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAG AGTTCCGGTTTGATCTTTCCAAGATCCCAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTAC AAGGACTACATCCGGGAACGCTTCGACAATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGA GCACTTGGGCAGGGAATCGGATCTCTTCCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCT GGCTGGTGTTTGACATCACAGCCACCAGCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTG CAGCTCTCGGTGGAGACGCTGGATGGGCAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCA CGGGCCCCAGAACAAGCAGCCCTTCATGGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCA TCCGGTCCACGGGGAGCAAACAGCGCAGCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTG CGGATGGCCAACGTGGCAGGACTGGATCATCGCGCC

NOVld, CG103910-04 SEQ ID NO: 8 325 aa MW at Protein Sequence !37269.9kD

MHVRSLRAAAPHSFVALWAPLFL RSA ADFS DNEVHSSFIHRRLRSQERREMQREI SILGLPHRP RPHLQGKHNSAPMF LDLY AMAVEEGGGPGGQGFSYPYKAVFSTQGPPLASLQDSHFLTDADMVMSF VNLVEHDKEFFHPRYHHREFRFD SKIPEGEAVTAAEFRIYKDYIRERFDNETFRISVYQVLQEHLGR ESDLFL DSRT WASEEG LVFDITATSNH VVNPRHNLGLQLSVETLDGQSINPKliAG IGRHGPQN KQPFMVAFFKATEVHFRSIRSTGSKQRSQNRSKTPKNQEALRMANVAGLDHRA

NOVle, 13382317 SNP CG103910-02 SEQ ID NO: 9 SNP at position 1193 DNA Sequence ORF Start: ATG at 1 fORF Stop: TGA at

1042

ATGCACGTGCGCTCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGGCACCCCTGTTCCTGC TGCGCTCCGCCCTGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTCATCCACCGGCGCCTCCG CAGCCAGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCGCGCCCG CACCTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGCGGTGGAGG AGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCCAGGGCCCCCC TCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTCGTCAACCTCGTG GAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGATCTTTCCAAGATCC CAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCCGGGAACGCTTCGACAA TGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGGGAATCGGATCTCTTCCTG CTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGACATCACAGCCACCAGCAACC ACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGGAGACGCTGGATGGGCAGAGCAT CAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAACAAGCAGCCCTTCATGGTGGCTTTC TTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGGGAGCAAACAGCGCAGCCAGAACCGCT CCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAACGTGGCAGGTCCACTTCATCAACCCGGAAA CGGTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCAATGCCATCTCCGTCCTCTACTTCGATGACAGCTC CAACGTCATCCTGAAGAAATACAGAAACATGGTGGTCCGGGCCTGTGGCTGCCACTAGCTCCTCCGAGAA

TTCAGACCCTTTGGGGCCAAGTTTTTCTGGATCCTCCATTGCTCGCCTTGGCCAGGAACCAGCAGACCAA

CTCCCTTTTGTGAGACCTTCCCCTCCCTATCCCC

NOVle, 13382317 SNP CG103910-02J SEQ ID NO: 10 325 aa SNP: No change in Protein Sequence JProtein sequence HVRSLRAAAPHSFVAL APLF RSA ADFS DNEVHSSFIHRRLRSQERRE QREILSILGLPHRP RPH QG HNSAPMFMLD YNAMAVEEGGGPGGQGFSYPY AVFSTQGPPLASLQDSHFLTDADMVMSF VNLVEHD EFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIY DYIRERFDNETFRISVYQVQEH GR ESD FL DSRT ASEEG LVFDITATSNH VVNPRHNLGLQLSVET DGQSINP LAGLIGRHGPQN KQPF VAFFKATEVHFRSIRSTGSKQRSQNRSKTPKNQEA RMANVAGPLHQPGNGAQALLCAHAAQC HLRPLLR

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table IB. Table IB. Comparison of the NOV1 protein sequences.

NOVla MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILS

NOVlb MHVRSLRAAAPHSFVALWAPLFLLRS LADFSLDNEVHSSFIHRRLRSQERREMQREILS

NOVlc MHVRSLRAAAPHSFVAL APLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILS

NOVld MHVRS RAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILS

NOVla ILGLPHRPRPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFST GPPLAS

NOVlb ILGLPHRPRPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLAS

NOVlc ILGLPHRPRPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLAS

NOVld I G PHRPRPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLAS

NOVla LQDSHF TDADMVMSFVNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFR1YKDY

NOVlb LQDSHFLTDADMVMSFVNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDY

NOVlc QDSHFLTDADMVMSFVNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDY

NOVld LQDSHF TDADMVMSFVNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDY

NOVla IRERFDNETFRISVYQVLQEHLGRESDLFLLDSRTL ASEEGWLVFDITATSNHWVVNPR

NOVlb IRERFDNETFRISVYQVLQEHLGRESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPR

NOVlc IRERFDNETFRISVYQVLQEHLGRESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPR

NOVld IRERFDNETFRISVYQVLQEHLGRESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPR

NOVla HNLGLQLSVETLDGQSINPKLAGLIGRHGPQNK PFMVAFFKATEVHFRSIRSTGSKQRS

NOVlb HNLGLQLSVETLDGQSINPKLAGLIGRHGPQNKQPF VAFFKATEVHFRSIRSTGSKQRS

NOVlc HNLGLQLSVETLDGQSINPKLAGLIGRHGPQNKQPFMVAFFKATEVHFRSIRSTGSKQRS

NOVld HNLGLQLSVETLDGQSINPKLAGLIGRHGPQNKQPFMVAFFKATEVHFRSIRSTGSKQRS

NOVla QNRSKTPKNQEALRMANVAG PLHQPGN GAQALLCA

NOVlb QNRSKTPKNQEALRMANVAG LDHRA

NOVlc QNRSKTPKNQEALRMANVAENSSSDQRQACKKHELYVSFRDLG QD IIAPEGYAAYYCE

NOVld QNRSKTPKNQEALRMANVAG LDHRA

NOVla HAAQCHLRPLLR- NOVlb NOVlc GECAFPLNSYMNATNHAIVQTLVHFINPETVPKPCCAPTQLNAISVLYFDDSSNVILKKY NOVld

NOVla NOVlb NOVlc RNMVVRACGCH NOVld

NOVla (SEQ ID NO 2)

NOVlb (SEQ ID NO 4)

NOVlc (SEQ ID NO

NOVld (SEQ ID NO

Further analysis of the NOVla protein yielded the following properties shown in Table IC.

Table IC. Protein Sequence Properties NOVla

SignalP analysis: Cleavage site between residues 30 and 31

PSORT II analysis:

PSG: a new signal peptide prediction method N-region: length 7; pos.chg 2; neg.chg 0 H-region: length 17; peak value 9.51 PSG score: 5.11

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 0.94 possible cleavage site: between 29 and 30

>» Seems to have a cleavable signal peptide (1 to 29)

ALOM: Klein et al's method for TM region allocation Init position for calculation: 30

Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 6.10 (at 124) ALOM score: 6.10 (number of TMSs: 0)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 14 Charge difference: -5.5 C(-1.5) - N( 4.0) N >= C: N-terminal side will be inside

MITDISC: discrimination of mitochondrial targeting seq R content: 3 Hyd Moment(75): 6.00 Hyd Moment(95): 9.57 G content: 0 D/E content: 1 S/T content: 3 Score: -0.96

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 35 LRSIAL

NUCDISC: discrimination of nuclear localization signals pat4 : none pat : none bipartite: none content of basic residues: 11.5% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals:

XXRR-like motif in the N-terminus: HVRS none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none NMYR: N-myristoylation pattern : none

Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none

Tyrosines in the tail: none

Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs : none checking 71 PROSITE riboso al protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none

NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6

COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23) :

44.4 %: extracellular, including cell wall

22.2 %: Golgi

11.1 % : vacuolar

11.1 %: nuclear

11.1 %: endoplasmic reticulum

» prediction for CG103910-02 is exc (k=9)

A search of the NOVla protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table ID.

In a BLAST search of public sequence databases, the NOVla protein was found to have homology to the proteins shown in the BLASTP data in Table IE.

PFam analysis predicts that the NOVla protein contains the domains shown in the Table IF.

Example 2.

The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.

Table 2A. NOV2 Sequence Analysis

NOV2a, CGI 06298-02 JSEQ ID NO: 11 1162 bp DNA Sequence ORF Start: ATG at 19 JORF Stop: TGA at 832

CTACTGAGAATATCTAACATGTTGTTACTAATCAATGTCATTCTGACCTTGTGGGTTTCCTGTGCTAA jTGGACAAGTGAAACCTTGTGATTTTCCAGACATTAAACATGGAGGTCTATTTCATGAGAATATGCGTA GACCATACTTTCCAGTAGCTGTAGGACAATCTTACTCCTATTACTGTGACCAAAATTTTGTGACTCCT TCAGGAAGTTACTGGGATTACATTCACTGCACACAAGATGGGTGGTTGCCAACAGTCCCATGCCTCAG AACATGCTCAAAATCAGATATAGAAATTGAAAATGGATTCATTTCTGAATCTTCCTCTATTTATATTT TAAATAAAGAAATACAATATAAATGTAAACCAGGATATGCAACAGCAGATGGAAATTCTTCAGGTTCA ATTACATGTTTGCAAAATGGATGGTCAGCACAACCAATTTGCATTAAATTTTGTGATATGCCTGTTTT TGAGAATTCCAGAGCCAAGAGTAATGGCATGCGGTTTAAGCTCCATGACACATTGGACTACGAATGCT ACGATGGATATGAAATCAGTTATGGAAACACCACAGGTTCCATAGTGTGTGGTGAAGATGGGTGGTCC CATTTCCCAACATGTTATAATTCTTCAGAAAAGTGTGGGCCTCCTCCACCTATTAGCAATGGTGATAC CACCTCCTTTCTACTAAAAGTGTATGTGCCACAGTCAAGAGTCGAGTACCAATGCCAGTCCTACTATG AACTTCAGGGTTCTAATTATGTAACATGTAGTAATGGAGAGTGGTCGGAACCACCAAGATGCATACGT ATCCACTTCTGCAGATGATCATGTCCAAGTTTGAGCTCCAAACTATGCAAGTGGCAAGACTGAAGAAG AAATTAGTATCCTCAAATCAAAATAGTTTACAAGTATCTTCAAACTTGATTTCATAGAAAAGTGTTAG

GTTTCAGAGATAAATTCTGAGTCTCAAATTTGATTGAATGGGGAGATGGACACTCCTAAGATGGGTTT

CACAGCAAAAGCATTACCTCTTCTCACAATCAAGAACAGGAAAGGATTATAATTATCTGAAGTATAAG iATCAGTTCCATGATACAAGCAAGACTTTCAGTCTTCAAAACTAAAGAAGCAAAGAGCATTCAAGCACA

GAATTC

NOV2a, CGI 06298-02 SEQ ID NO: 12 271 aa MW at 30635. lkD Protein Sequence

MLLLI VILTL VSCANGQVKPCDFPDI HGGLFHENMRRPYFPVAVGQSYSYYCDQNFVTPSGSYWD YIHCTQDGWLPTVPCLRTCSKSDIEIENGFISESSSIYILNKEIQYKCKPGYATADGNSSGSITCLQN G SAQPICIKFCDMPVFENSRAKSNGMRFKLHDTLDYECYDGYEISYG TTGSIVCGEDG SHFPTCY NSSEKCGPPPPISNGDTTSFLLKVYVPQSRVEYQCQSYYELQGSNYVTCSNGE SEPPRCIRIHFCR

NOV2b, CG106298-01 SEQ ID NO: 13 2033 bp

DNA Sequence ORF Start: ATG at 78 lORF TAA at 1812

AATAATAATGAAAGATTTCAAACCCCAAACAGTGCAACTGAAACTTTTGCATTACTATACTACTGAGA

ATATCTAACATGTTGTTACTAATCAATGTCATTCTGACCTTGTGGGTTTCCTGTGCTAATGGACAAGA

AGTGAAACCTTGTGATTTTCCAGAAATTCAACATGGAGGTCTATATTATAAGAGTTTGCGTAGACTAT ACTTTCCAGCAGCTGCAGGACAATCTTATTCCTATTACTGTGATCAAAATTTTGTGACTCCTTCAGGA AGTTACTGGGATTACATTCATTGCACACAAGATGGTTGGTCACCAACGGTCCCATGCCTCAGAACATG CTCAAAATCAGATGTAGAAATTGAAAATGGATTCATTTCTGAATCTTCCTCTATTTATATTTTAAATG AAGAAACACAATATAATTGTAAACCAGGATATGCAACAGCAGATGGAAATTCTTCAGGATCAATTACA TGTTTGCAAAATGGATGGTCAACACAACCAATTTGCATTAAATTTTGTGATATGCCTGTTTTTGAGAA TTCCAGAGCCAAGAGTAATGGCATGTGGTTTAAGCTCCATGACACATTGGACTATGAATGCTATGATG GATATGAAAGCAGTTATGGAAACACCACAGATTCCATAGTGTGTGGTGAAGATGGCTGGTCCCATTTG CCAACATGCTATAATTCTTCAGAAAGCTGTGGGCCTCCTCCACCTATTAGCAATGGAGATACCACGTC CTTCCCGCAAAAAGTGTATCTGCCATGGTCAAGAGTCGAGTACCAGTGCCAGTCCTACTATGAACTTC AGGGTTCTAAATATGTAACATGTAGTAATGGAGACTGGTCAGAACCACCAAGATGCATATCAATGAAA CCTTGTGAGTTTCCAGAAATTCAACATGGACATCTATATTATGAGAATACGCGTAGACCATACTTTCC AGTAGCTACAGGACAATCTTACTCCTATTACTGTGACCAAAATTTTGTGACTCCTTCAGGAAGTTACT GGGATTACATTCACTGCACACAAGATGGGTGGTTGCCAACAGTCCCATGCCTCAGAACATGCTCAAAA TCAGATATAGAAATTGAAAATGGATTCATTTCTGAATCTTCCTCTATTTATATTTTAAATAAAGAAAT ACAATATAAATGTAAACCAGGATATGCAACAGCAGATGGAAATTCTTCAGGTTCAATTACATGTTTGC AAAATGGATGGTCAGCACAACCAATTTGCATTAT^ATTTTGTGATATGCCTGTTTTTGAGAATTCCAGA GCCAAGAGTAATGGCATGCGGTTTAAGCTCCATGACACATTGGACTACGAATGCTACGATGGATATGA AATCAGTTATGGAAACACCACAGGTTCCATAGTGTGTGGTGAAGATGGGTGGTCCCATTTCCCAACAT GTTATAATTCTTCAGAAAAGTGTGGGCCTCCTCCACCTATTAGCAATGGTGATACCACCTCCTTTCTA CTAAAAGTGTATGTGCCACAGTCAAGAGTCGAGTACCAATGCCAGTCCTACTATGAACTTCAGGGTTC TAATTATGTAACATGTAGTAATGGAGAGTGGTCGGAACCACCAAGATGCATACATCCATGTATAATAA CTGAAGAAAACATGAATAAAAATAACATACAGTTAAAAGGAAAAAGTGACATAAAATATTATGCAAAA ACAGGGGATACCATTGAATTTATGTGTAAATTGGGATATAATGCGAATACATCAGTTCTATCATTTCA AGCAGTGTGTAGGGAAGGCATAGTGGAATACCCCAGATGCGAATAAGGCAGCATTGTTACCCTAAATG TATGTCCAACTTCCACTTCTCACTCTTATGGTCTCAAAGCTTGCAAAGATAGCTTCTGATATTGTTGT

AATTTCTACTTTATTTCAAAGAAAATTAATATAATAGTTTCAATTTGCAACTTAATATGTTCTCAAAA

ATATGTTAAAACAAACTAAATTATTGCTTATGCTTGTACTAAAATAATAAAAACTACCCTT

NOV2b, CGI 06298-01 !SEQ ID NO: 14 578 aa MW at 65309.0kD Protein Sequence ML INVI TLVSCANGQEV PCDFPEIQHGGLYYKS RRLYFPAAAGQSYSYYCDQNFV PSGSY DYIHCTQDGWSPWPCLRTCSKSDVEIENGFISESSSIYILNΞETQYNCKPGYATADGNSSGSITC Q NGWSTQPICIKFCDMPVFENSRAKSNGMWFKLHDTLDYECYDGYESSYGNTTDSIVCGEDGWSH PTC YNSSESCGPPPPISNGDTTSFPQKVYLPWSRVΞYQCQSYYELQGSKYVTCSNGDWSEPPRCISMKPCE FPEIQHGHLYYENTRRPYFPVATGQSYSYYCDQNFVTPSGSYDYIHCTQDG PTVPCLRTCSKSDI EIENGFISESSSIYI KEIQYKCKPGYATADGNSSGSITCLQNGWSAQPICI FCDMPVFENSRAKS NGRFKLHDTLDYECYDGYEISYGNTTGSIVCGEDGWSHFPTCYNSSEKCGPPPPISNGDTTSFL KV Y PQSRVEYQCQS YELQGSNY CSNGE SE PRCIH CII EE 1NKN IQ GKSDI YY TGD TIEFMCKLGYNANTSVLSFQAVCREGIVEYPRCE

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 2B.

Table 2B. Comparison of the NOV2 protein sequences.

NOV2a LLINVILTLWVSCANGQ-VKPCDFPDIKHGG FHENMRRPYFPVAVGQSYSYYCDQNF

NOV2b MLLLINVILTLWVSCANGQEVKPCDFPEIQHGGLYYKSLRRLYFPAAAGQSYSYYCDQNF

NOV2a VTPSGSY DYIHCTQDG LPTVPCLRTCSKSDIEIENGFISESSSIYILNKEIQYKCKPG

NOV2b VTPSGSYWDYIHCTQDGWSPTVPCLRTCSKSDVEIENGFISESSSIYILNEETQYNCKPG

NOV2a YATADGNSSGSITCLQNGWSAQPICIKFCDMPVFENSRAKSNGMRFKLHDTLDYECYDGY

NOV2b YATADGNSSGSITCLQNGWSTQPICIKFCDMPVFENSRAKSNGMWFKLHDTLDYECYDGY

NOV2a EISYGNTTGSIVCGEDGWSHFPTCYNSSEKCGPPPPISNGDTTSFLLKVYVPQSRVEYQC

NOV2b ESSYGNTTDSIVCGEDGWSHLPTCYNSSESCGPPPPISNGDTTSFPQKVYLPWSRVEYQC

NOV2a QSYYELQGSNYVTCSNGE SEPPRCIRIHFCR

NOV2b QSYYELQGSKYVTCSNGDWSEPPRCISMKPCEFPEIQHGHLYYENTRRPYFPVATGQSYS

NOV2a

NOV2b YYCDQNFVTPSGSY DYIHCTQDG LPTVPCLRTCSKSDIEIENGFISESSSIYILNKE1

NOV2a

NOV2b QYKCKPGYATADGNSSGSITCLQNG SAQPICIKFCDMPVFENSRAKSNGMRFKLHDTLD

NOV2a

NOV2b YECYDGYEISYGNTTGSIVCGEDGWSHFPTCYNSSEKCGPPPPISNGDTTSFL KVYVPQ

NOV2a

NOV2b SRVEYQCQSYYE QGSNYVTCSNGE SEPPRCIHPCIITEENMNKN1Q GKSDIKYYA

NOV2a

NOV2b KTGDTIEFMCKLGYNANTSVLSFQAVCREGIVEYPRCE

NOV2a (SEQ ID NO: 12) NOV2b (SEQ ID NO: 14)

Further analysis of the NO V2a protein yielded the following properties shown in Table 2C.

Table 2C. Protein Sequence Properties NO 2a

SignalP analysis: Cleavage site between residues 19 and 20 PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 0; pos.chg 0; neg.chg 0 H-region: length 20; peak value 9.20 PSG score: 4.80

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 1.38 possible cleavage site: between 18 and 19

»> Seems to have a cleavable signal peptide (1 to 18)

ALOM: Klein et al's method for TM region allocation Init position for calculation: 19

Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 8.27 (at 137) ALOM score: 8.27 (number of TMSs: 0)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 9 Charge difference: 0.0 C( 1.0) - N( 1.0) N >= C: N-terminal side will be inside

MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.43 Hyd Moment (95) : 4.91 G content: 1 D/E content: 1 S/T content: 2 Score: -5.38

Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found

NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 7.4% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals: none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2: none NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none

NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 76.7

COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23)

44.4 %: extracellular, including cell wall

33.3 %: nuclear

22.2 % : mitochondrial

» prediction for CG106298-02 is exc (k=9)

A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D.

In a BLAST search of public sequence databases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2E.

PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2F.

Example 3.

The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.

Table 3A. NO 3 Sequence Analysis

|NOV3a, CGI 10590-02 jSEQ ID NO: 15 1487 bp [DNA Sequence ORF Start: ATG at 112 ORF Stop: TGA at 1303 jGGAGAAGGCCAGTGCCCAGGTTAGTGAGCAGTGCCCGGCGCCCGCTTCCCTCACCTCCTTTTCCAGCC

TTTGCACAGCTTGAAGGTTCTGTCACCTTTTGCAGTGGTCCAAATGAGAAAAAAGTGGAAAATGGGAG

GCATGAAATACATCTTTTCGTTGTTGTTCTTTCTTTTGCTAGAAGGAGGCAAAACAGAGCAAGTAAAA CATTCAGAGACATATTGCATGTTTCAAGACAAGAAGTACAGAGTGGGTGAGAGATGGCATCCTTACCT GGAACCTTATGGGTTGGTTTACTGCGTGAACTGCATCTGCTCAGAGAATGGGAATGTGCTTTGCAGCC GAGTCAGATGTCCAAATGTTCATTGCCTTTCTCCTGTGCATATTCCTCATCTGTGCTGCCCTCGCTGC CCAGACTCCTTACCCCCAGTGAACAATAAGGTGACCAGCAAGTCTTGCGAGTACAATGGGACAACTTA CCAACATGGAGAGCTGTTCGTAGCTGAAGGGCTCTTTCAGAATCGGCAACCCAATCAATGCACCCAGT GCAGCTGTTCGGAGGGAAACGTGTATTGTGGTCTCAAGACTTGCCCCAAATTAACCTGTGCCTTCCCA GTCTCTGTTCCAGATTCCTGCTGCCGGGTATGCAGAGGAGATGGAGAACTGTCATGGGAACATTCTGA TGGTGATATCTTCCGGCAACCTGCCAACAGAGAAGCAAGACATTCTTACCACCGCTCTCACTATGATC CTCCACCAAGCCGACAGGCTGGAGGTCTGTCCCGCTTTCCTGGGGCCAGAAGTCACCGGGGAGCTCTT ATGGATTCCCAGCAAGCATCAGGAACCATTGTGCAAATTGTCATCAATAACAAACACAAGCATGGACA AGTGTGTGTTTCCAATGGAAAGACCTATTCTCATGGCGAGTCCTGGCACCCAAACCTCCGGGCATTTG GCATTGTGGAGTGTGTGCTATGTACTTGTAATGTCACCAAGCAAGAGTGTAAGAAAATCCACTGCCCC AATCGATACCCCTGCAAGTATCCTCAAAAAATAGACGGAAAATGCTGCAAGGTGTGTCCAGGTAAAAA AGCAAAAGAACTTCCAGGCCAAAGCTTTGACAATAAAGGATACTTCTGCGGGGAAGAAACGATGCCTG TGTATGAGTCTGTATTCATGGAGGATGGGGAGACAACCAGAAAAATAGCACTGGAGACTGAGAGACCA CCTCAGGCATTCTCCAGCACTTCCATATTGAGAAGATCTCCAAGAGGATGTTTGAGGAGCTTCCTCAC TTCAAGCTGGTGACCAGAACAACCCTGAGCCAGTGGAAGATCTTCACCGAAGGAGAAGCTCAGATCAG CCAGATGTGTTCAAGTCGTGTATGCAGAACAGAGCTTGAAGATTTAGTCAAGGTTTTGTACCTGGAGA

GATCTGAAAAGGGCCACTGTTAGGCAAGACAGACAGTATTGGATAGGGTAAAGCAAGAA

NOV3a, CGI 10590-02 SEQ ID NO: 16 397 aa MW at 44841.9kD Protein Sequence

MRKKWKMGGMKYIFSLLFFLLLEGGKTEQVKHSETYCMFQDKKYRVGERWHPYLEPYGLVYCVNCICS ENGNVLCSRVRCPNVHCLSPVHIPHLCCPRCPDSLPPVNNKVTSKSCEYNGTTYQHGELFVAEGLFQN RQPNQCTQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCRGDGELSWEHSDGDIFRQPANREARH SYHRSHYDPPPSRQAGGLSRFPGARSHRGALMDSQQASGTIVQIVINN HKHGQVCVSNGKTYSHGES WHPNLRAFGIVΞC/LCTCNVTKQECKKIHCPNRYPCKYPQKIDGKCCVCPGKKAKELPGQSFDN GY FCGEETMPVYESVFMEDGETTRKIALETERPPQAFSSTSILRRSPRGCLRSFLTSSW

|NOV3b, CGI 10590-01 SEQ ID NO: 17 1440 bp

DNA Sequence RF Start: ATG at 18 JORF Stop: TAG at 1374

TGAGAAAAAAGTGGAAAATGGGAGGCATGAAATACATCTTTTCGTTGTTGTTCTTTCTTTTGCTAGAA

GGAGGCAAAACAGAGCAAGTAAAACATTCAGAGACATATTGCATGTTTCAAGACAAGAAGTACAGAGT GGGTGAGAGATGGCATCCTTACCTGGAACCTTATGGGTTGGTTTACTGCGTGAACTGCATCTGCTCAG AGAATGGGAATGTGCTTTGCAGCCGAGTCAGATGTCCAAATGTTCATTGCCTTTCTCCTGTGCATATT CCTCATCTGTGCTGCCCTCGCTGCCCAGAAGACTCCTTACCCCCAGTGAACAATAAGGTGACCAGCAA GTCTTGCGAGTACAATGGGACAACTTACCAACATGGAGAGCTGTTCGTAGCTGAAGGGCTCTTTCAGA ATCGGCAACCCAATCAATGCACCCAGTGCAGCTGTTCGGAGGGAAACGTGTATTGTGGTCTCAAGACT TGCCCCAAATTAACCTGTGCCTTCCCAGTCTCTGTTCCAGATTCCTGCTGCCGGGTATGCAGAGGAGA TGGAGAACTGTCATGGGAACATTCTGATGGTGATATCTTCCGGCAACCTGCCAACAGAGAAGCAAGAC ATTCTTACCACCGCTCTCACTATGATCCTCCACCAAGCCGACAGGCTGGAGGTCTGTCCCGCTTTCCT GGGGCCAGAAGTCACCGGGGAGCTCTTATGGATTCCCAGCAAGCATCAGGAACCATTGTGCAAATTGT CATCAATAACAAACACAAGCATGGACAAGTGTGTGTTTCCAATGGAAAGACCTATTCTCATGGCGAGT CCTGGCACCCAAACCTCCGGGCATTTGGCATTGTGGAGTGTGTGCTATGTACTTGTAATGTCACCAAG CAAGAGTGTAAGAAAATCCACTGCCCCAATCGATACCCCTGCAAGTATCCTCAAAAAATAGACGGAAA ATGCTGCAAGGTGTGTCCAGGTAAAAAAGCAAAAGAAGAACTTCCAGGCCAAAGCTTTGACAATAAAG GCTACTTCTGCGGGGAAGAAACGATGCCTGTGTATGAGTCTGTATTCATGGAGGATGGGGAGACAACC AGAAAAATAGCACTGGAGACTGAGAGACCACCTCAGGTAGAGGTCCACGTTTGGACTATTCGAAAGGG CATTCTCCAGCACTTCCATATTGAGAAGATCTCCAAGAGGATGTTTGAGGAGCTTCCTCACTTCAAGC TGGTGACCAGAACAACCCTGAGCCAGTGGAAGATCTTCACCGAAGGAGAAGCTCAGATCAGCCAGATG TGTTCAAGTCGTGTATGCAGAACAGAGCTTGAAGATTTAGTCAAGGTTTTGTACCTGGAGAGATCTGA AAAGGGCCACTGTTAGGCAAGACAGACAGTATTGGATAGGGTAAAGCAAGAAAACTCAAGCTGCAGCT GGACTGCAGGCT

NOV3b, CGI 10590-01 SEQ ID NO: 18 452 aa MW at 51425.5kD Protein Sequence

MGGMKYIFS LFFLLLEGGKTEQV HSETYCMFQDKKYRVGERWHPYLEP GLVYCVNCICSENGNVL CSRVRCPNVHCLSPVHIPHLCCPRCPEDSIiPPVNNKVTSKSCEYNGTTYQHGELFVAEGLFQNRQPNQ CTQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCRGDGELS EHSDGDIFRQPANREARHSYHRS HYDPPPSRQAGGLSRFPGARSHRGALMDSQQASGTIVQIVINNKHKHGQVCVSNGKTYSHGES HPNL RAFGIVECVLCTCNVTKQECKKIHCPNRYPCKYPQKIDGKCCKVCPGKKAKEELPGQSFDNKGYFCGE ETMPVYESVFMEDGETTRKIALETERPPQVEVHVWTIRKGILQHFHIEKISKRMFEELPHFKLVTRTT LSQWKIFTEGEAQISQMCSSRVCRTELEDLVKVLYLERSEKGHC

NOV3c, 13382325 SNP SEQ ID NO: 19 1487 bp, SNP: T/C at CGI 10590-02 position 454 DNA Sequence ORF Start: ATG at 112 ORF Stop: 1303

GGAGAAGGCCAGTGCCCAGGTTAGTGAGCAGTGCCCGGCGCCCGCTTCCCTCACCTCCTTTTCCAGCCTTT

GCACAGCTTGAAGGTTCTGTCACCTTTTGCAGTGGTCCAAATGAGAAAAAAGTGGAAAATGGGAGGCATGA

AATACATCTTTTCGTTGTTGTTCTTTCTTTTGCTAGAAGGAGGCAAAACAGAGCAAGTAAAACATTCAGAG ACATATTGCATGTTTCAAGACAAGAAGTACAGAGTGGGTGAGAGATGGCATCCTTACCTGGAACCTTATGG GTTGGTTTACTGCGTGAACTGCATCTGCTCAGAGAATGGGAATGTGCTTTGCAGCCGAGTCAGATGTCCAA ATGTTCATTGCCTTTCTCCTGTGCATATTCCTCATCTGTGCTGCCCTCGCTGCCCAGACTCCTTACCCCCA GTGAACAATAAGGTGACCAGCAAGTCTCGCGAGTACAATGGGACAACTTACCAACATGGAGAGCTGTTCGT AGCTGAAGGGCTCTTTCAGAATCGGCAACCCAATCAATGCACCCAGTGCAGCTGTTCGGAGGGAAACGTGT ATTGTGGTCTCAAGACTTGCCCCAAATTAACCTGTGCCTTCCCAGTCTCTGTTCCAGATTCCTGCTGCCGG GTATGCAGAGGAGATGGAGAACTGTCATGGGAACATTCTGATGGTGATATCTTCCGGCAACCTGCCAACAG AGAAGCAAGACATTCTTACCACCGCTCTCACTATGATCCTCCACCAAGCCGACAGGCTGGAGGTCTGTCCC GCTTTCCTGGGGCCAGAAGTCACCGGGGAGCTCTTATGGATTCCCAGC7VAGCATCAGGAACCATTGTGCAA ATTGTCATCAATAACAAACACAAGCATGGACAAGTGTGTGTTTCCAATGGAAAGACCTATTCTCATGGCGA GTCCTGGCACCCAAACCTCCGGGCATTTGGCATTGTGGAGTGTGTGCTATGTACTTGTAATGTCACCAAGC AAGAGTGTAAGAAAATCCACTGCCCCAATCGATACCCCTGCAAGTATCCTCAAAAAATAGACGGAAAATGC TGCAAGGTGTGTCCAGGTAAAAAAGCAAAAGAACTTCCAGGCCAAAGCTTTGACAATAAAGGATACTTCTG CGGGGAAGAAACGATGCCTGTGTATGAGTCTGTATTCATGGAGGATGGGGAGACAACCAGAAAAATAGCAC TGGAGACTGAGAGACCACCTCAGGCATTCTCCAGCACTTCCATATTGAGAAGATCTCCAAGAGGATGTTTG AGGAGCTTCCTCACTTCAAGCTGGTGACCAGAACAACCCTGAGCCAGTGGAAGATCTTCACCGAAGGAGAA GCTCAGATCAGCCAGATGTGTTCAAGTCGTGTATGCAGAACAGAGCTTGAAGATTTAGTCAAGGTTTTGTA

CCTGGAGAGATCTGAAAAGGGCCACTGTTAGGCAAGACAGACAGTATTGGATAGGGTAAAGCAAGAA

NOV3c, 13382325 SNP ISEQ ID NO: 20 397 aa SNP: Cys to Arg at 115 CGI 10590-02 Protein Sequence

MR K KMGGMKYIFSLLFFLLLEGGKTEQVKHSETYCMFQDK YRVGERWHPYLEPYGLVYCVNCICSENG NVLCSRVRCPNVHCLSPVHIPHLCCPRCPDSLPPVNNKVTSKSREYNGTTYQHGELFVAEGLFQNRQPNQC TQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCRGDGELSWEHSDGDIFRQPANREARHSYHRSHYDP PPSRQAGGLSRFPGARSHRGALMDSQQASGTIVQIVINNKHKHGQVCVSNGKTYSHGES HPNLRAFGIVE CVLCTCNVTKQECKKIHCPNRYPCKYPQKIDGKCCKVCPGKKAKELPGQSFDNKGYFCGEETMPVYESVFM EDGETTRKIALETERPPQAFSSTSILRRSPRGCLRSFLTSS

NOV3d, 13382326 SNP SEQ ID NO: 21 1440 bp SNP: A/G at CGI 10590-02 756 DNA Sequence ORF Start: ATG at ORF Stop: end of 112 sequence GGAGAAGGCCAGTGCCCAGGTTAGTGAGCAGTGCCCGGCGCCCGCTTCCCTCACCTCCTTTTCCAGCCTTT GCACAGCTTGAAGGTTCTGTCACCTTTTGCAGTGGTCCAAATGAGAAAAAAGTGGAAAATGGGAGGCATGA AATACATCTTTTCGTTGTTGTTCTTTCTTTTGCTAGAAGGAGGCAAAACAGAGCAAGTAAAACATTCAGAG ACATATTGCATGTTTCAAGACAAGAAGTACAGAGTGGGTGAGAGATGGCATCCTTACCTGGAACCTTATGG GTTGGTTTACTGCGTGAACTGCATCTGCTCAGAGAATGGGAATGTGCTTTGCAGCCGAGTCAGATGTCCAA ATGTTCATTGCCTTTCTCCTGTGCATATTCCTCATCTGTGCTGCCCTCGCTGCCCAGACTCCTTACCCCCA GTGAACAATAAGGTGACCAGCAAGTCTTGCGAGTACAATGGGACAACTTACCAACATGGAGAGCTGTTCGT AGCTGAAGGGCTCTTTCAGAATCGGCAACCCAATCAATGCACCCAGTGCAGCTGTTCGGAGGGAAACGTGT ATTGTGGTCTCAAGACTTGCCCCAAATTAACCTGTGCCTTCCCAGTCTCTGTTCCAGATTCCTGCTGCCGG GTATGCAGAGGAGATGGAGAACTGTCATGGGAACATTCTGATGGTGATATCTTCCGGCAACCTGCCAACAG AGAAGCAAGACATTCTTACCACCGCTCTCACTATGATCCTCCACCGAGCCGACAGGCTGGAGGTCTGTCCC GCTTTCCTGGGGCCAGAAGTCACCGGGGAGCTCTTATGGATTCCCAGCAAGCATCAGGAACCATTGTGCAA ATTGTCATCAATAACAAACACAAGCATGGACAAGTGTGTGTTTCCAATGGAAAGACCTATTCTCATGGCGA GTCCTGGCACCCAAACCTCCGGGCATTTGGCATTGTGGAGTGTGTGCTATGTACTTGTAATGTCACCAAGC AAGAGTGTAAGAAAATCCACTGCCCCAATCGATACCCCTGCAAGTATCCTCAAAAAATAGACGGAAAATGC TGCAAGGTGTGTCCAGGTAAAAAAGCAAAAGAACTTCCAGGCCAAAGCTTTGACAATAAAGGATACTTCTG CGGGGAAGAAACGATGCCTGTGTATGAGTCTGTATTCATGGAGGATGGGGAGACAACCAGAAAAATAGCAC TGGAGACTGAGAGACCACCTCAGGCATTCTCCAGCACTTCCATATTGAGAAGATCTCCAAGAGGATGTTTG AGGAGCTTCCTCACTTCAAGCTGGTGACCAGAACAACCCTGAGCCAGTGGAAGATCTTCACCGAAGGAGAA GCTCAGATCAGCCAGATGTGTTCAAGTCGTGTATGCAGAACAGAGCTTGAAGATTTAGTCAAGGTTTTGTA CCTGGAGAGATCTGAAAAGGGCCACTGTTAGGCAAGACAGACAGTATTGGATAGGGTAAAGCAAGAA

NOV3d, 13382326 SNP SEQ ID NO: 22 397 aa SNP: No change in protein CGI 10590-02 sequence Protein Sequence

MRKKWKMGGMKYIFSLLFFL.LLEGGKTΞQVKHSETYC FQDK YRVGERWHPYLEPYGLVYCVNCICSENG NVLCSRVRCPNVHCIiSPVHIPHLCCPRCPDS PPVNNKVTSKSCEYNGTTYQHGELFVAEGLFQNRQPNQC TQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCRGDGELSWEHSDGDIFRQPANREARHSYHRSHYDP PPSRQAGGLSRFPGARSHRGALMDSQQASGTIVQIVINNKHKHGQVCVSNGKTYSHGESWHPNLRAFGIVE CVLCTClWTKQECKKIHCPlSrRYPCKYPQKIDGKCCKVCPGK AKELPGQSFDNKGYFCGEETMPVYESVFM EDGETTRKIALETERPPQAFSSTSILRRSPRGCLRSFLTSSW

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 3B.

Table 3B. Comparison of the NOV3 protein sequences.

NOV3a MRKK GGMKYIFSLLFFLLLEGGKTEQVKHSETYCMFQDKKYRVGERHPYLEPYGLV

NOV3b MGGMKYIFSLLFFLLLEGGKTEQVKHSETYCMFQDKKYRVGER HPYLEPYGLV

NOV3a YCVNCICSENGNVLCSRVRCPNVHCLSPVHIPHLCCPRCP-DSLPPVNNKVTSKSCEYNG

NOV3b YCVNCICSENGNVLCSRVRCPNVHCLSPVHIPHLCCPRCPEDSLPPVNNKVTSKSCEYNG

NOV3a TTY HGELFVAEGLFQNRQPNQCTQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCR

NOV3b TTYQHGELFVAEGLFQNRQPNQCTQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCR

NOV3a GDGELSWEHSDGDIFRQPANREARHSYHRSHYDPPPSRQAGGLSRFPGARSHRGALMDSQ

NOV3b GDGELSWEHSDGDIFRQPANREARHSYHRSHYDPPPSRQAGGLSRFPGARSHRGALMDSQ

NOV3a QASGTIVQIVINNKHKHGQVCVSNGKTYSHGESWHPNLRAFGIVECVLCTCNVTKQECKK

NOV3b QASGTIVQIVINNKHKHGQVCVSNGKTYSHGESWHPNLRAFGIVECVLCTCNVTKQECKK

NOV3a IHCPNRYPCKYPQKIDGKCCKVCPGKECAK-ELPGQSFDNKGYFCGEETMPVYESVFMEDG

NOV3b IHCPNRYPCKYPQKIDGKCCKVCPGKKAKEELPGQSFDNKGYFCGEETMPVYESVFMEDG

NOV3a ETTRKIALETERPP QAFSSTSILRRS PRGCLRS-FLTSS —

NOV3b ETTRKIALETERPPQVEVHVWTIRKGILQHFHIEKISKRMFEELPHFKLVTRTTLSQ KI

NOV3a

NOV3b FTEGEAQISQMCSSRVCRTELEDLVKVLYLERSEKGHC

NOV3a (SEQ ID NO: 16)

NOV3b (SEQ ID NO: 18)

Further analysis of the NOV3a protein yielded the following properties shown in Table 3C.

Table 3C. Protein Sequence Properties NOV3a

SignalP analysis: Cleavage site between residues 28 and 29

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 11; pos.chg 5; neg.chg 0 H-region: length 11; peak value 12.14 PSG score: 7.74

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -1.64 possible cleavage site: between 27 and 28

>» Seems to have a cleavable signal peptide (1 to 27)

ALOM: Klein et al's method for TM region allocation Init position for calculation: 28

Tentative number of TMS(s) for the threshold 0.5: number of TMS(s) .. fixed PERIPHERAL Likelihood = 1.80 (at 277) ALOM score: 1.80 (number of TMSs: 0)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 13 Charge difference: -6.5 C(-0.5) - N( 6.0) N >= C: N-terminal side will be inside

MITDISC: discrimination of mitochondrial targeting seg R content: 1 Hyd Moment(75): 6.12 Hyd Moment (95): 9.66 G content: 2 D/E content: 1 S/T content: 1 Score: -4.32

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 12 MRK|KW

NUCDISC: discrimination of nuclear localization signals pat4: none pat7: PGKKAKE (4) at 323 bipartite: none content of basic residues: 13.1% NLS Score: -0.13

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals :

XXRR-like motif in the N-terminus: RKK none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs : none

NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 94.1

COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23)

66.7 %: extracellular, including cell wall

11.1 % : mitochondrial

11.1 %: vacuolar

11.1 %: nuclear

» prediction for CG110590-02 is exc (k=9)

A search of the NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3D.

In a BLAST search of public sequence databases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3E.

PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3F.

Example 4.

The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A.

Table 4A. NOV4 Sequence Analysis

NOV4a, CGI 14555-01 SEQ ID NO: 23 1710 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: TAA at 1534

GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAG

ATGACACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGT GGGGTGCCAGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCA TGGACGTCCAATAGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCG GTGGACTTGTGGGGACATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTG GCCAATAATGGGTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGA AATGCTCATCGTGGGACGCTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGT ACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGC ATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATA CCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCC CACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGT AAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCT GGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCA TGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCT GGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGT CTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGG GCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTG AGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGC TCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTA GTCTTTGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAG AACCTATGCAGAAATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCG ACTCAGCTGTCACTGATGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAAT TATGTCAAAAACAGGATTGTCTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTAT

TGGGAAGCTTAAATGAATTGAAGCTATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGT

ACTAATCTAA

NOV4a, CGI 14555-01 SEQ ID NO: 24 507 aa MW at 55327.3kD Protein Sequence

MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNESWERRHGRPI DPDTLTLL SVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLA-SJNGFAISAALLMACSLQAGAFEMLIV GRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKEST PYLFGV IWPAWQLLSLPFLPDSPRYLLLEKHNEARAVKAFQTFLG ADVSQEVEEVLAESRVQRSIRLVSVL ELLRAPYVR QVV VIVTMACYQLCGLNAI FYTNSIFG AGIPLAKIPYVTLSTGGIETLAAVFSGL VIEHLGRRPLLIGGFGLMGLFFGTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEF FQQSQRPAAFIIAGTVN LSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAE ISQAFSKRNKAYPPEEKIDSAVTDGKINGRP

!NOV4b, 247847074 SEQ ID NO: 25 1203 bp

DNA Sequence JORF Start: at 1 JORF Stop: end of sequence

TTGTACAAAAAAGCAGGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAA TAATGGGTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGC TCATCGTGGGACGTTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTC AGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGG CGTGTTCACTGGGCAGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGT TTGGAGTGATTGTGGTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGC TACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGC AGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGT CCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCC TGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGAT CCCTCCGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCT CTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTC TTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTAT CGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTG GTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCC AACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTT TGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCT ATGCAGAAATCAGCCAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC

NOV4b, 247847074 SEQ ID NO: 26 401 aa MW at 43391.7kD Protein Sequence

LYKKAGSAAAPFTGTRKHTLIiANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYL SEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIWPAWQLLSLPFLPDSPR YLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVR QVVTVIVTMA CYQLCGLNAI FYTNSIFGKAGIPPAKIPYVTLSTGGIETIiAAVFSGLVIEHLGRRPLLIGGFGLMGL FFGTLTITLTLQDHAPWVPYLSIVGIIΛIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLS NFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEGKGGRA

NOV4c, 247847070 SEQ ID NO: 27 1087 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

GGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAA

TTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGT

TTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACC

CAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGC

AGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTG

GTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGA

GAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACATTTCCCAAG

AGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTG

CTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTG

TGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGA

TCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGACCACGCCCCC

TGGGTCCCCTACCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGG

CATCCCGTTCATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAG

GCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGAC

ACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCC

TGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC

NOV4c, 247847070 SEQ ID NO: 28 362 aa MW at 39164.5kD Protein Sequence

GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISP KEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKEST PYLFGVIWPAWQLLSLPFLPDSPRYLLLE KHNEARAVKAFQTFLGKADISQEVEEVI-AESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLC GLNAI FYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSDHAP VPYLSIVGILAIIASFCSGPGG IPFILTGEFFQQSQRPAAFIIAGTVN LSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLP ΞTKNRTYAEISQAFLEGKGGRA

NOV4d, 247847055 SEQ ID NO: 29 1189 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

GGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAA

TTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGC

TTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACC

CAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGC

AGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTG

GTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGA

GAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAG

AGGTAGAGGAGGTCCTGGCTGAGAGCCACGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTG CTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTG TGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGA TCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATT GAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGACCCT CACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGG CCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAG CAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGG GCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTA TCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGC CAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC

NOV4d, 247847055 SEQ ID NO: 30 396 aa MW at 42768.9kD Protein Sequence

GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISP KEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIWPAWQLLSLPFLPDSPRYLLLE KHNΕARAVT^FQTFLG ADVSQEVEEVIjAESHVQRSIRLVSVLELLRAPYVR QVVTVIVTMACYQLC GLNAIWFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTL TITLTLQDHAPWVPYLSIVGIIJAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVG LLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEGKGGRA

NOV4e, 247847059 SEQ ID NO: 31 1189 bp

DNA Sequence JORF Start: at 1 JORF Stop: end of sequence

GGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAA

TTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGC

TTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACC

CAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGC

AGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTG

GTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGA

GAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACATTTCCCAAG

AGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTG

CTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTG

TGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGA

TCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATT

GAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGACCCT

CACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGG

CCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAG

CAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGG

GCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTA

TCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGC

CAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC

NOV4e, 247847059 SEQ ID NO: 32 396 aa !MW at 42801.9kD Protein Sequence

GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISP KEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKEST PYLFGVIWPAWQLLSLPFLPDSPRYLLLE KHl^ARAVKAFQTFLGKUDISQEVEEVIJ^SRVQRSIRLVSVLELLRAPYVR QVVTVIVTMACYQLC GLNAI FYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTL TITLTLQDHAP VPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVG LLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEG GGRA

NOV4f, 247847047 SEQ ID NO: 33 1189 bp

DNA Sequence ORF Start: at 1 JORF Stop: end of sequence

GGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAA

TTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGC

TTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACC

CAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGC

AGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTG

GTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGA GAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAG AGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTG CTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTG TGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGA TCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATT GAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGACCCT CACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGG CCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAG CAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGG GCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTA TCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGC CAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC

NOV4f, 247847047 SEQ ID NO: 34 396 aa MW at 42803.9kD Protein Sequence

GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISP KEIRGSLGQVTAIFICIGVFTGQIiLGLPELLGKEST PYLFGVIWPAWQLLSLPFLPDSPRYLLLE KHNEARAVKAFQTFLGKADVSQEVEEVIJAESRVQRS IRLVSVLELLRAPYVRWQVVTVIVTMACYQLC GLNAI FYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTL ITLTLQDHAP VPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVN LSNFAVG LLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEGKGGRA

NOV4g, CGI 14555-02 SEQ ID NO: 35 1682 bp

DNA Sequence uFstart- ATG at 14 JORF Stop: TAA at 1634

GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAG

ATGACACCAGCCACGCCAGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGTCCACCTGAGGAGT GGGGTGCCAGGTGGAAGGAGAAGAAAGGACTGGTCCTGCTCGCTCCTCGTGGCCTCCCTCGCGGGCGC CTTCGGCTCCCCCTTCCTCTACGGCTACAACCTGTCGGTGGTGAATGCCCCCACCCCGTACATCAAGG CCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAATAGACCCAGACACTCTGACTCTGCTC TGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGACATTAATTGTGAAGATGATTGG AAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAATTTCTGCTGCATTGCTGA TGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAGATGCTCATCGTGGGACGCTTCATCATGGGCATAGAT GGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTC TCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCCG AGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCAG CTGCTGAGCCTTCCCTTTCTCCTGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAG AGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGG CTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTC CGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTG GTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGA GTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGA CCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGGCCCTCACCATCACGCTGACCCT GCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCT GCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCT GCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCAT TCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTATCTACC TGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGGCATTTTCCAAAAGG AACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGATGGTAAGATAAATGGAAGGCC TTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTG

NOV4g, CGI 14555-02 SEQ ID NO: 36 540 aa MW at 58796.3kD Protein Sequence

MARKQNRNSKELGLVPLTDDTSHARPPGPGRALLECVHLRSGVPGGRRRKDWSCSLLVASLAGAFGSP FLYGYNLSWNAPTPYIKAFYNES ERRHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLG RKHTLLANNGFAISAALLMACSLQAGAFE LIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQV TAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIWPAWQLLSLPFLLDSPRYLLLEKHNEARAVKA FQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVR QVVTVIVTMACYQLCGLNAIWFYTN SIFG AGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGALTITLTLQDHA PWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVN LSNFAVGLLFPFIQKSL DTYCFLVFATICITGAIYLYFVLPΞTKNRTYAEISQAFS RNKAYPPEEKIDSAVTDGKINGRP

NOV4h, CGI 14555-03 SEQ ID NO: 37 1757 bp

DNA Sequence ORF Start: ATG at 14 ORF Stop: TAA at 1709

GTCACTGAGACCCATGGCAAGGAAGCAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAG

ATGACACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGT GGGGTGCCAGGTGGAAGGAGAAGAAAGCAGCCTCTACGGAGCACCTCCTCTGCAGCAGGCTCCTCAAC AACATATGTGGCCAGTGCTGCTATTAAGATCCCATTTCACAGGTGGGCAAGCTTAGCCCCAGAAAAGT CAAGTCACTTGCTCAGACTCCTACAGCTGAGGGGACTGGCCCTGGAGGTAAAGCTGATATCACTTGGC TCAAAGCCCCAAAGCTCTATCTCGTGGCTGGTGGCACTAGAGGAGACAAACGAGATTGGCAGAGACTG GTCCTGCTCGCTCCTCGTGGCCTCCCTCGCGGGCGCCTTCGGCTCCTCCTTCCTCTACGGCTACAACC TGTCGGTGGTGAATGCCCCCACCCCGCACACTTTGCTGGCCAATAATGGGTTTGCAATTTCTGCTGCA TTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCATCATGGG CATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCC GTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGC CTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGT TGTCCAGCTGCTGAGCCTTCCCTTTCTCCTGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACG AGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAG GTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCC CTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATG CAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTC ACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGG ACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGGCCCTCACCATCACGC TGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGGCCATCATCGCC TCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCG GCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCC CATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCT ATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGGCATTTTC CAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGATGGTAAGATAAATG GAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTG

NOV4h, CGI 14555-03 SEQ ID NO: 38 565 aa MW at 61112.6kD Protein Sequence

MARKQNRNS ELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKQPLRSTSSAAGSSTTYVA SAAIKIPFHR ASIAPEKSSHLLRLLQLRGLALEVKLISLGSKPQSSISWLVALEETNEIGRD SCSL LVASIAGAFGSSFLYGYNLSVVNAPTPHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGG VALSV PMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLG EST PYIiFGVIWPAWQLL SLPFLLDSPRYL LEKHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVR QVVTVIVTMACYQLCGLNAIWFYTNSIFGKΑGIPLA IPYVTLSTGGIETIiAAVFSGLVIEHLGRRPL LIGGFGLMGLFFGALTITLTLQDHAP VPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAF 11 GTVN LSNFAVGLLFPFIQKSLDTYCFLVFA ICITGAIYLYFVLPETKNRTYAEISQAFSKRNK AYPPEEKIDSAV DGKINGRP

NOV4 CGI 14555-04 jSEQ ED NO: 39 1502 bp

DNA Sequence ORF Start: ATG at 14 JORF Stop: TAA at 1454

GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAG

ATGACACCAGCCACGCCAGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGTCCACCTGAGGAGT GGGGTGCCAGGTGGAAGGAGAAGAAAGGACTGGTCCTGCTCGCTCCTCGTGGCCTCCCTCGCGGGCGC CTTCGGCTCCCCCTTCCTCTACGGCTACAACCTGTCGGTGGTGAATGCCCCCACCCCGTACATCAAGG CCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAATAGACCCAGACACTCTGACTCTGCTC TGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGACATTAATTGTGAAGATGATTGG AAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAATTTCTGCTGCATTGCTGA TGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAGATGCTCATCGTGGGACGCTTCATCATGGGCATAGAT GGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTC TCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCCG AGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCAG CTGCTGAGCCTTCCCTTTCTCCTGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAG lAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGG CTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTC CGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTG GTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGA GTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGCATCCCGTTCATCTTGACTGGTGAGTTC TTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGC TGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAA TTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAA ATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCAC TGATGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACA GGATTG

NO V4i, CGI 14555-04 SEQ ID NO: 40 480 aa MW at 52522.9kD Protein Sequence

MAR QNRNSKELGLVPLTDDTSHARPPGPGRALLECVHLRSGVPGGRRR D SCSLLVASLAGAFGSP FLYGYNLSWNAPTPYIKAFYNES ERRHGRPIDPDTLTLL SVTVSIFAIGGLVGTLIVKMIGKVLG RKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYIiSEISPKEIRGSLGQV TAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIWPAWQLLSLPFLLDSPRYLLLEKHNEARAVKA FQTFLGKAIDVSQEVEEVIiAESRVQRSIRLVSVLELLRAPYVR QVVTVIVTMACYQLCGLNAIWFYTN SIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVGLL FPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVTDGKI NGRP

NOV4J, 13379365 SNP in SEQ ID NO: 41 SNP: G/A at position 86 CGI 14555-01 ORF Start: ATG at 14 ORF Stop: TAA at 1535 DNA Sequence

GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATGA

CACCAGCCACGCCAGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTGCC

AGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAAT

AGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGAC

ATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAAT

TTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCAT

CATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGAT

CCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCT

GCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCA

GCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGC

TGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAG

CCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGT

GGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAG

CATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGAC

TTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGG

GCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTA

CCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT

GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTC

CAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTA

GTCTTTGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACC

TATGCAGAAATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCT

GTCACTGATGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAAC

AGGATTGTCTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATTGGGAAGCTTAAATGA

ATTGAAGCTATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTAATCTAA

NOV4J, 13379365 SNP in SEQ ID NO: 42 507aa SNP: Gly to CGI 14555-01 Arg at position Protein Sequence 25

MARKQNRNSKΞLGLVPLTDDTSHARPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNESWERRHGRPIDPDT LTLL SVTVSIFAIGGLVGTLIVKMIGKVLGRKHTL1ANNGFAISAALLMACSLQAGAFEMLIVGRFIMGID GGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKEST PYLFGVIWPAWQLLSL, PFLPDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVBAESRVQRSIRLVSVLELLRAPYVR QVVTVI VTMACYQLCGLNAIWFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGL FFGTLTITLTLQDHAP VPYIiSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVN LSNFAV GLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRN AYPPEEKIDSAVTDGKIN GRP

NOV4k, 13379364 SNP in SEQ ID NO:43 SNP: G/A at position 97 CGI 14555-01 ORF Start: ATG at 14 ORF Stop: TAA at 1535 DNA Sequence

GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATGA

CACCAGCCACGCCGGGCCTCCAGGACCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTGCC AGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAAT AGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGAC ATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAAT TTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCAT CATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGAT CCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCT GCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCA GCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGC TGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAG CCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGT GGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAG CATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGAC TTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGG GCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTA CCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTC CAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGC TACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGA AATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGA TGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTGT CTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATTGGGAAGCTTAAATGAATTGAAGC

TATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTAATCTAA

NOV4k, 13379364 SNP SEQ ID NO: 507 aa SNP : Gly to Gly at position 28 CGI 14555-01 44 Protein Sequence

MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNES ERRHGRPIDPDT LTLL SVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGID GGVALSVLPMYLSEISPKEIRGSLGQV AIFICIGVFTGQLLGLPELLGKESTWPYLFGVIWPAWQLLSL PFLPDSPRYLLLEKHNEARAVKAFQTFLGK-ADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVR QVVTVI VTMACYQLCGIjNAI FYTNSIFGKAGIPIiAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGL FFGTLTITLTLQDHAP VPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVN LSNFAV GLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVTDGKIN GRP

NOV41, 13379363 SNP CGI 14555-01 jSEQ ID NO:45 SNP: A/G at position 289 DNA Sequence ORF Start: ATG at ORF Stop: TAA at 1535 position 14

GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATGA

CACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTGCC AGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAAT AGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGAC GTTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAAT TTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCAT CATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGAT CCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCT GCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCA GCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGC TGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAG CCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGT GGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAG CATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGAC TTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGG GCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTA CCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCA TGCAGGCACCGTCAACTGGCTCTC CAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGC TACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGA AATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGA TGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTGT CTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATTGGGAAGCTTAAATGAATTGAAGC

TATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTAATCTAA

NOV41, 13379363 SNP SEQ ID NO: 507 SNP: no change in the protein CGI 14555-01 46 aa sequence Protein Sequence

MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNESWERRHGRPIDPDT LTLL SV VSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGID GGVALSVLPMYLSEISPKEIRGSLGQV AIFICIGVFTGQLLGLPELLGKESTWPYIiFGVIWPAWQLLSL PFLPDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVR QVVTVI VTMACYQLCGLNAI FY NSIFGKAGIPLA IPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGL FFGTLTITLTLQDHAP VPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVN LSNFAV GLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKls TYAEISQAFS RN AYPPEEKIDSAVTDGKIN GRP

NOV4m, 13379362 SNP CGI 14555-01 EQ ID NO: 47 [ShyTc/T at position 672 DNA Sequence ORF Start: ATG at ORF Stop: TAA at 1535 position 14

GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATGA

CACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTGCC AGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAAT AGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGAC ATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAAT TTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCAT CATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGAT CCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCT GCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCA GCTGCTGAGCCTTCCCTTTCTCCTGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGC TGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAG CCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGT GGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAG CATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGAC TTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGG GCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTA CCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTC CAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGC TACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGA AATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGA TGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTGT CTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATTGGGAAGCTTAAATGAATTGAAGC

TATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTAATCTAA

NOV4m, 13379362 SEQ ID NO: 48 1507 aa ISNP: Pro to Leu at position 220 SNP CGI 14555-01 Protein Sequence

MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNESWERRHGRPIDPD TLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMG IDGGVAIiSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKEST PYLFGVIWPAWQL LSLPFLLDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVR QV VTVIVT ACYQLCGLNAI FYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGF GLMGLFFGTLTITLTLQDHAP VPYIiSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVN LSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSA VTDGKINGRP

NOV4n, 13379620 SNP jSEQ ID NO: 49 SNP: T/C at position 963

CGI 14555-01 ORF Start: ATG at ORF Stop: TAA at 1535 DNA Sequence position 14

GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATG

ACACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTG CCAGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCC AATAGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGG GGACATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTT GCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACG CTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCA AGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTT CTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGC CGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACG AGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTC CTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGT CCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGT TCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGATCCCATACGTCACCTTGAGTACA GGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCT CATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACG CCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGT GGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGG CACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCT ACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACC AAAAACAGAACCTATGCAGAAATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAA AATCGACTCAGCTGTCACTGATGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACA ATTATGTCAAAAACAGGATTGTCTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATT

GGGAAGCTTAAATGAATTGAAGCTATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTA

ATCTAA

NOV4n, 13379620 SNP CGI 14555- SEQ ID NO: 50 507 aa SNP: Leu to Pro at

01 position 317

Protein Sequence

MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNES E RRHGRPIDPDTLTL SVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLM ACSLQAGAFEMLIVGRFI GIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTG QLLGLPELLGKEST PYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQTFL GKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIV MACYQLCGLNAIWFY TNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTLT ITLTLQDHAP VPY S VGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWL SNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRN AY PPEEKIDSAVTDGKINGRP

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 4B. Table 4B. Comparison of the NOV4 protein sequences.

NOV4a MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRK- NOV4b NOV4c NOV4d NOV4e NOV4f NOV4g MARKQNRNSKELGLVPLTDDTSHARPPGPGRALLECVHLRSGVPGGRRRKD NOV4h MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKQPLRSTSSAA NO 4i MARKQNRNSKELGLVPLTDDTSHARPPGPGRALLECVRLRSGVPGGRRRKDW

NO 4a -YIKAFYNES ER NOV4b NOV4c NOV4d NOV4e NOV4f NOV4g SCSLLV AS AGAFGSPFLYGYNLS VVNAPTPYIKAFYNESWER NOV4h GSSTTYVASAAIKIPFHRWASLAPEKSSHLLRLLQLRGLALEVKLISLGSKPQSSISWLV NOV4i SCSLLV ASLAGAFGSPFLYGYNLS VVNAPTPYIKAFYNESWER

NOV4a RHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLM NOV4b LYKKAGSAAAPFTGTRKHTLLANNGFAISAALLM NOV4c GSAAAPFTGTRKHTLLANNGF_AISAALLM NOV4d GSAAAPFTGTRKHTLLANNGFAISAALLM NOV4e GSAAAPFTGTRKH_TLLANNGF_AISA_AL_LM NOV4f GSAAA_PFTG_TRKHTLLANN_GFAI_SA_ALLM NOV4g RHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLM NOV4h ALEETNEIGRD SCSLLVASLAGAFGSSFLYGYNLSWNAPTPHTLLANNGFAISAALLM NOV4i RHGRPIDPDTLTLL SVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLM

NOV4 ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4b ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4c ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NO 4d ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4e ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4f ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4g ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4h ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4i ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT

NOV4a GQLLGLPELLGKEST PYLFGVIWPAWQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4b GQLLGLPELLGKEST PYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4c GQLLGLPELLGKEST PYLFGVIWPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4d GQLLGLPELLGKESTWPYLFGVI VPAWQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4e GQLLGLPELLGKESTWPYLFGVIWPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4f GQLLGLPELLGKESTWPYLFGVIWPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4g GQLLGLPELLGKEST PYLFGVIVVPAVVQLLSLPFLLDSPRYLLLEKHNEARAVKAFQT NOV4h GQLLGLPELLGKEST PYLFGVIVVPAWQLLSLPFLLDSPRYLLLEKHNEARAVKAFQT NOV4i GQLLGLPELLGKEST PYLFGVIVVPAVVQLLSLPFLLDSPRYLLLEKHNEARAVKAFQT

NOV4a FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4b FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVR QWTVIVTMACYQLCGLNAI NOV4c FLGKADISQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4d FLGKADVSQEVEEVLAESHVQRSIRLVSVLELLRAPYVR QWTVIVTMACYQLCGLNAI NOV4e FLGKADISQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4f FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVR QVVTVIVTMACYQLCGLNAI NOV4g FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4h FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4i FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI

NOV4a FYTNSIFGKAGI PLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4b WFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF N0V4c WFYTNSIFGKAGI PPAKIPYVTLSTGGIETLAAVFS NOV4d WFYTNSIFGKAGI PPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4e WFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGL GLFF NOV4f WFYTNSIFGKAGIPLAKIPYVTLSTGG1ETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4g WFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4h WFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4i WFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFS

NOV4a GTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4b GTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4c DHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4d GTLTITLTLQDHAPWVPYLSI GILAII SFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4e GTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4f GTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4g GALTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4h GALTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4i _GI_PF_IL_TGEFF_QQ_SQR_PA_AFIIA_G

NOV4a TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFS NOV4b TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4c TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4d TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4e TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4f TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4g TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFS NOV4h TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFS NOV4i TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFS

NOV4a KRNKAYPPEEKIDSAVTDGKINGRP NOV4b E GKG-GRA NOV4c _E GKG-_GRA NOV4d B _GK_G-_GRA NOV4e _B GKG-_GRA NOV4f _{B G}K_G-_GRA NOV4g KRNKAYPPEEKIDSAVTDGKINGRP NOV4h KRNKAYPPEEKIDSAVTDGKINGRP NOV4i KRNKAYPPEEKIDSAVTDGKINGRP

NOV4a (SEQ ID NO 24) NOV4b (SEQ ID NO 26) NOV4c (SEQ ID NO 28) NOV4d (SEQ ID NO 30) NOV4e (SEQ ID NO 32) NOV4f (SEQ ID NO 34) NOV4g (SEQ ID NO 33) NOV4h (SEQ ID NO 38) NOV4i (SEQ ID NO 40) Further analysis of the NOV4a protein yielded the following properties shown in Table 4C.

Table 4C. Protein Sequence Properties NOV4a

SignalP analysis: No Known Signal Sequence Predicted

PSORT II analysis:

PSG : a new signal peptide prediction method

N-region : length 11 ; pos . chg 4 ; neg . chg 1 H-region : length 7 ; peak value 1 . 99 PSG score : -2. 41

GvH : von Heijne ' s method for signal seq. recognition GvH score ( threshold: -2 . 1 ) : -4 . 97 possible cleavage site : between 24 and 25

»> Seems to have no N-terminal signal peptide

ALOM: Klein et al ' s method for TM region allocation

Init position for calculation: 1

Tentative number of TMS(s) for the threshold 0 .5: 9

INTEGRAL Likelihood = -6.48 Transmembrane 79 - 95

INTEGRAL Likelihood = -1.75 Transmembrane 120 - 136

INTEGRAL Likelihood = 0.47 Transmembrane 140 - 156

INTEGRAL Likelihood = -3.40 Transmembrane 171 - 187

INTEGRAL Likelihood = -5.73 Transmembrane 200 - 216

INTEGRAL Likelihood = -0.32 Transmembrane 283 - 299

INTEGRAL Likelihood = -2.23 Transmembrane 351 - 367

INTEGRAL Likelihood = -5.89 Transmembrane 378 - 394

INTEGRAL Likelihood = -5.26 Transmembrane 449 - 465

PERIPHERAL Likelihood = 1.01 {at 419)

ALOM score: -6.48 (number of TMSs: 9)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 86 Charge difference: 5.0 C( 4.5) - N(-0.5) C > N: C-terminal side will be inside

>» membrane topology: type 3b

MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 10.97 Hyd Moment (95) : 13.25 G content: 1 D/E content: 2 S/T content: 2 Score: -3.59

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 17 NRN|SK

NUCDISC: discrimination of nuclear localization signals pat4: RRRK (5) at 47 pat7: PGGRRRK (5) at 44 bipartite: none content of basic residues: 9.1% NLS Score: 0.27 ; KDEL : ER retention motif in the C-terminus : none

ER Membrane Retention Signals:

XXRR-like motif in the N-terminus: ARKQ none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1

COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues

esults (k = 9/23) :

66 7 endoplasrαic reticulum

11 1 %: vacuolar

11 1 mitochondrial

11 1 5- . Golgi

» prediction for CG114555-01 is end (k=9) A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4D.

In a BLAST search of public sequence databases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4E.

PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4F.

Example 5.

The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A.

Table 5A. NOV5 Sequence Analysis

NOV5a, CGI 81662-01 SEQ ID NO: 51 1492 bp DNA Sequence ORF Start: ATG at 4 ORF Stop: TAA at 940

GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACC

CCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGG AAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGG CATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGC AATAATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAA GAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCC TGGCAGCATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGGACCA ACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCA CTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTA CCACATAATGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCC TAATCTGTTAAATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTG TGGATATCTATGAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTA GAGTTATGTGAAATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAG ATCCCTTCAAAGCAAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAG AAGAACTTGATGGAATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCC

TTCCCTTTGCCTGTGGTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTT

IGGGTGCTGCTGCTACTCAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGA

GGAGGAAGAAAAAGTCCCATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCAT

CAGCTCCTCCCTCAGTGGTACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTA

ATGGATGTGAGGTAGCCGAAGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCT

GCACACTCACATTATCTTGCTATCACTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATT lATAGCTGTATCTAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACAAA

NO V5a, CGI 81662-01 SEQ ID NO: 52 312 aa MW at 36492.6kD Protein Sequence

MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRH FRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADIl^QDAKNΥHAW QHRQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVP HNESAWNYLKGILQDRGLSKYPl^ILLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALE LCEILAKEKDTIRKEY RYIGRSLQSKHSTENDSPTNVQQ

NOV5b, CGI 81662-02 SEQ ID NO: 53 1487 bp DNA Sequence ORF Start: ATG at 17 ORF Stop: TAA at 953

CGGCCGCGTCGACGAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGC

AGCCGGCGCAACCCCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCG GCCGAGGCTGGGGAAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTA TGTCCTATACAGGCATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGA ACTACATCACTGCAATAATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTA GTGGAATGGCTAAGAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAA GAATTATCATGCCTGGCAGCATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGC AGTATGTGGACCAACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTT ATTTCTAACACCACTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAAT GATTAAACTAGTACCACATAATGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTC TTTCCAAATATCCTAATCTGTTAAATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTA ATTGCCTTTCTTGTGGATATCTATGAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCT TAATAAAGCATTAGAGTTATGTGAAATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGA GATACATTGGAAGATCCCTTCAAAGCAAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAA TAACACCATCCAGAAGAACTTGATGGAATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCAC IACGAGAGTGGTCCTTCCCTTTGCCTGTGGTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGA

ACTGATGCTCCTTGGGTGCTGCTGCTACTCAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAG

TCATTGGATGGGAGGAGGAAGAAAAAGTCCCATAAAGGAACTTTTGTAGTCTTATCAACATATAATCT

[AATCCCTTAGCATCAGCTCCTCCCTCAGTGGTACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGG

TCACTTGTATGTAATGGATGTGAGGTAGCCGAAGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCA

TCAGAGCTGGTCTGCACACTCACATTATCTTGCTATCACTGTAACCAACTAATGCCAAAAGAACGGTT

TTGTAATAAAATTATAGCTGTATCTAAAAACAAAAAAAAAAAAAAAAAACCAAAAAAAT

NO V5b, CGI 81662-02 SEQ ID NO: 54 312 aa MW at 36492.6kD Protein Sequence

MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRH FRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDAKNYHA QHRQV /IQEFKXiWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNϋRAVLEREVQYTLEMI LVP HNESA NYLKGILQDRGLSKYPNLIiNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALE LCEILAKEKDTIRKEY RYIGRSLQSKHSTENDSPTNVQQ

NOV5c, 307686795 SEQ ID NO: 55 1487 bp DNA Sequence ORF Start: at 2 ORF Stop: TAA at 953

CGGCCGCGTCGACGAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGC AGCCGGCGCAACCCCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCG GCCGAGGCTGGGGAAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTA TGTCCTATACAGGCATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGA ACTACATCACTGCAATAATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTA GTGGAATGGCTAAGAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAA GAATTATCATGCCTGGCAGCATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGC AGTATGTGGACCAACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTT ATTTCTAACACCACTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAAT GATTAAACTAGTACCACATAATGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTC TTTCCAAATATCCTAATCTGTTAAATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTA ATTGCCTTTCTTGTGGATATCTATGAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCT TAATAAAGCATTAGAGTTATGTGAAATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGA GATACATTGGAAGATCCCTTCAAAGCAAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAA TAACACCATCCAGAAGAACTTGATGGAATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCAC ACGAGAGTGGTCCTTCCCTTTGCCTGTGGTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGA

ACTGATGCTCCTTGGGTGCTGCTGCTACTCAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAG

TCATTGGATGGGAGGAGGAAGAAAAAGTCCCATAAAGGAACTTTTGTAGTCTTATCAACATATAATCT lAATCCCTTAGCATCAGCTCCTCCCTCAGTGGTACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGG

TCACTTGTATGTAATGGATGTGAGGTAGCCGAAGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCA TCAGAGCTGGTCTGCACACTCACATTATCTTGCTATCACTGTAACCAACTAATGCCAAAAGAACGGTT TGTAATAAAATTATAGCTGTATCTAAAAACAAAAAAAAAAAAAAAAAACCAAAAAAAT

NOV5c, 307686795 SEQ ID NO: 56 317 aa MW at 37049.2kD Protein Sequence

GRVDEMAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSY VLYRHFRRVLLKSLQKDLHEEMNYITAIIΞEQPKNYQV HHRRVLVEWLRDPSQELEFIADILNQDAK NYHA QHRQ VIQΞFliWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEM IKLVPHNESA NYIi GILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDIIi NKALELCEILAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ

NOV5d, CG181662-03 SEQ ID NO: 57 1344 bp DNA Sequence ORF Start: ATG at 17 ORF Stop: TAA at 1154

TCGGTCCGCAGCCGAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGC AGCCGGCGCAACCCCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCG GCCGAGGCTGGGGAAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTA TGTCCTGTACAGGGACAGAGCAGAATGGGCTGATATAGATCCGGTGCCGCAGAATGATGGCCCCAATC CCGTGGTCCAGATCATTTATAGTGACAAATTTAGAGATGTTTATGATTACTTCCGAGCTGTCCTGCAG CGTGATGAAAGAAGTGAACGAGCTTTTAAGCTAACCCGGGATGCTATTGAGTTAAATGCAGCCAATTA TACAGTGTGGCATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACT ACATCACTGCAATAATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTG GAATGGCTAAGAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAA TTATCATGCCTGGCAGCATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGT ATGTGGACCAACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATT TCTAACACCACTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGAT TAAACTAGTACCACATAATGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTT CCAAATATCCTAATCTGTTAAATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATT GCCTTTCTTGTGGATATCTATGAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAA TAAAGCATTAGAGTTATGTGAAATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGAT ACATTGGAAGATCCCTTCAAAGCAAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAA CACCATCCAGAAGAACTTGATGGAATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACG

AGAGTTCCTTCCCTTTTGTGGTGTAAAAGTGCATCACACAGGTATTGCTTTTTACAGACTGATGCTCC

TTGGTGCTGCTGCATCTATCTCAGACTAGCTCTAGTATGTGATCTCTAAGCA

NOV5d, CGI 81662-03 SEQ ID NO: 58 379 aa MW at 44408.2kD Protein Sequence

MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVliYRD RAEWADIDPVPQOT3GPNPWQIIYSDKFRDVYDYFRAVLQRDERSERAFKLTRDAIELNAANYTVWHF RRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDAKNYHA Q HRQ VIQEFKLWDΪTELQYVDQLLKEDVR]1NSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKIJVPH NESANYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALEL CEILAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ

NOV5e, CGI 81662-04 SEQ ID NO: 59 1156 bp DNA Sequence ORF Start: ATG at 11 ORF Stop: end of sequence

CACCGGATCCATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGG

CGCAACCCCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAG GCTGGGGAAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCT GTACAGGGACAGAGCAGAATGGGCTGATATAGATCCGGTGCCGCAGAATGATGGCCCCAATCCCGTGG TCCAGATCATTTATAGTGACAAATTTAGAGATGTTTATGATTACTTCCGAGCTGTCCTGCAGCGTGAT GAAAGAAGTGAACGAGCTTTTAAGCTAACCCGGGATGCTATTGAGTTAAATGCAGCCAATTATACAGT GTGGCATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCA CTGCAATAATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGG CTAAGAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCA TGCCTGGCAGCATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGG ACCAACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAAC ACCACTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACT AGTACCACATAATGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAAT ATCCTAATCTGTTAAATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTT CTTGTGGATATCTATGAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGC ATTAGAGTTATGTGAAATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTG GAAGATCCCTTCAAAGCAAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAA

NOV5e, CGI 81662-04 SEQ ID NO: 60 379 aa MW at 44408.2kD Protein Sequence

MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRD RAΞ ADIDPVPQNDGPNPVVQIIYSDKFRDVYDYFRAVLQRDERSERAFKLTRDAIELNAANYTV HF

RRVLLKSLQKDLHEEMNΎITAIIEEQPKNYQV HHRRVLVE LRDPSQELEFIADILNQDA NYHA Q

HRQ VIQEFKL DHELQYVDQLLKEDVRNNSV NQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPH NESA NYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDIIJNKALEL CEIIIA EKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ

NOV5f, 13382357 SNP CGI 81662-01 SEQ ID NO: 1492 bp, SNP atposition DNA Sequence 61 310 C/T

ORF Start: ORF Stop: TAA at 940 [ATG at 4 _ j

GAGATGGCGGCCΆCCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGC

CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA jGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGGCAT TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGTATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT GAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTGTGGATATCTAT GAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG

GTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT

CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC

CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG

TACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA

AGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC

TATCACTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAAA

AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACAAA

NOV5f, 13382357 SNP CGI 81662- SEQ ID NO: 312 aa SNP: His to Tyr at 01 162 position 103

Protein Sequence

MAATEGVGEAAQGGΞPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRHF RRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVYHRRVLVE RDPSQELEFIADILNQDAKNYHA QH RQ VIQEFKLWDNELQYVDQLLKEDλ^RNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNE SAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEI LAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ

NOV5g, 13377970 SNP CGI 81662-01 SEQ ID 1492 bp, SNP at position DNA Sequence NO: 63 457 G/C

ORF Start: ORF Stop: TAA at 940 ATG at 4

GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACCC CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA GCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGGCAT TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATCAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT GAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTGTGGATATCTAT G2AGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG

GTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT

CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC

CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG

TACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA iAGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC iTATCACTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAΆAAAAAAAAAAAAAACAAA

NOV5&T3377970 SNP SEQ ID NO: 64 312 SNP: Glu to Gin at CGI 81662-01 aa position 152 Protein Sequence

MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRHF RRVL KS QKD HEE^1 YITAIIEEQPKN Q HHRRVLVEW RDPSQE EFIADIL QD K HA QH RQWVIQEFKLWDNQLQYVDQLLKEDVRNNSVNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNE SANYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEI LAKEKDTIRKEY RYIGRSLQSKHSTENDSPTNVQQ

NOV5h, 13378241 SNP CG181662-01 SEQ ID 1492 bp, SNP at position DNA Sequence NO: 65 729 C/A

ORF Start: ORF Stop: TAA at 940 ATG at 4

GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACCC

CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA GCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGGCAT TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT GAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCATACCTAATTGCCTTTCTTGTGGATATCTAT GAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG

GTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT

CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC

CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG

TACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA

AGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC

TATCACTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAAA iAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACAAA

NOV5h, 13378241 SNP CG181662-01 SEQ ID 312 SNP: no change in the Protein Sequence j NO: 66 aa protein sequence

MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRHF RRVLLKSLQKIDLHEEMNYITAIIEEQPKNYQV HHRRVLVEWLRDPSQELEFIADIIjNQDAKNYHA QH RQVWIQEFKLWDNELQYVDQLLKEDVRNNSVlrøQRYF/ISlSrrTGYNDRAVLEREVQYTLEMIKLVPHNE SAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDN EDILNKALELCEI LAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ

NOV5i, 13377901 SNP CGI 81662-01 SEQ ID 1492 bp, SNP at position DNA Sequence NO: 67 1330 G/T

ORF ORF Stop: TAA at 940

Start: ATG at

4

GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACCC CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA GCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGGCAT TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC ;AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT IGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA !AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTGTGGATATCTAT GAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG

GTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT

CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC

CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG

TACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA

AGTTTGGTTCAGTAAGCATGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC

TATCACTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAAA

AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACAAA ^jNOV5i, 13377901 SNP CG181662-01 SEQ ID NO: 68 312 aa SNP: Not in coding Protein Sequence region jMAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRHF jRRVLLKSLQKDLHEEMNYITAIIEEQPKlvrYQV HHRRVLVEWLRDPSQELEFIADILNQDAKNYHAWQH jRQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNE SAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEI LAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ

|NOV5j, 13377900 SNP CG181662-01 SEQ ID 1492 bp, SNP at position DNA Sequence NO: 69 1385 A/C

ORF Start: I ORF Stop: TAA at 940 ATG at 4

GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACCC

CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA GCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGGCAT TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT GAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTGTGGATATCTAT GAAGACATGCTAGAAAATCAGTGTGACAA.TAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAAT-ACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG

GTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT

CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC

CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG iTACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA jAGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC

TATCCCTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAAA lAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACAAA

NOV5j, 13377900 SNP CG181662-01 SEQ ID NO: 70 j 312 aa SNP: Not in coding Protein Sequence region

MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRHF RRVLLKSLQKDLHEΞMNYITAIIEEQPKNYQV HHRRVLVE LRDPSQELEFIADILNQDAKNYHAWQH RQ VIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNE SAϊmYLKGILQDRG SKYP r I^Q LD Q SHSSPY IAFL DIYEDM E QCD KEDI ls^KA E CEI IiAKEKDTIRKEY RYIGRSLQSKHSTENDSP NVQQ A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 5B.

Table 5B. Comparison of the NOV5 protein sequences.

NOV5a MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF

NOV5b MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF

NOV5c GRVDEMAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF

NOV5d MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF

NOV5e MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF

NOV5a VSLDSPSYVLYR

NOV5b VSLDSPSYVLYR ^•

NOV5C VSLDSPSYVLYR

NOV5d VSLDSPSYVLYRDRAEWADIDPVPQNDGPNPVVQIIYSDKFRDVYDYFRAVLQRDERSER

NOV5e VSLDSPSYVLYRDRAE ADIDPVPQNDGPNPWQIIYSDKFRDVYDYFRAVLQRDERSER

NOV5a HFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQV HHRRVL

NOV5b HFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQV HHRRVL

N V5c HFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQV HHRRVL

NOV5d AFKLTRDAIELNAANYTV HFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVL

NOV5e AFKLTRDAIELNAANYTVHFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQV HHRRVL

N0V5a VEWLRDPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNS

NOV5b VE LRDPSQELEFIADILNQDAKNYHA QHRQWVIQEFKL DNELQYVDQLLKEDVRNNS

NOV5c VEWLRDPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNS

NOV5d VE LRDPSQELEFIADILNQDAKNYHA QHRQ VIQEFKL DNELQYVDQLLKEDVRNNS

NOV5e VEWLRDPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNS

NOV5a V NQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESANYLKGILQDRGLSKYPNL

NOV5b V NQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESANYLKGILQDRGLSKYPNL

NOV5c V NQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESA NYLKGILQDRGLSKYPNL

NOV5d V NQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESANYLKGILQDRGLSKYPNL

NOV5e VWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESANYLKGILQDRGLSKYPNL

NOV5a LNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY

NOV5b LNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY

NOV5c LNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY

NOV5d LNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY

NOV5e LNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY

NOV5a RYIGRSLQSKHSTENDSPTNVQQ

NOV5b WRYIGRSLQSKHSTENDSPTNVQQ

NOV5C WRYIGRSLQSKHSTENDSPTNVQQ

NOV5d WRYIGRSLQSKHSTENDSPTNVQQ

NOV5e WRYIGRSLQSKHSTENDSPTNVQQ

NOV5a (SEQ ID NO 52)

NOV5b (SEQ ID NO 54)

NOV5c (SEQ ID NO 56)

NOV5d (SEQ ID NO 58)

NOV5e (SEQ ID NO 60)

Further analysis of the NOV5a protein yielded the following properties shown in Table 5C. Table 5C. Protein Sequence Properties NOV5a

SignalP analysis: No Known Signal Sequence Predicted

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 9; pos.chg 0; neg.chg 2 H-region: length 5; peak value 0.00 PSG score: -4.40

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -11.19 possible cleavage site: between 13 and 14

>» Seems to have no N-terminal signal peptide

ALOM: Klein et al's method for TM region allocation Init position for calculation: 1

Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 6.42 (at 240) ALOM score: 6.42 (number of TMSs: 0)

MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 6.27 Hyd Moment (95) : 4.56 G content: 2 D/E content: 2 S/T content: 1 Score: -7.86

NUCDISC: discrimination of nuclear localization signals pat4 : none pat7: none bipartite: none content of basic residues: 9.9% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals : none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2 : 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1: none type 2 : none

NMYR: N-myristoylation pattern : none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none

Tyrosines in the tail: none

NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 55.5

COIL: Lupas ' s algorithm to detect coiled-coil regions

249 D 0.58

250 I 0.58

251 Y 0.82

252 E 0.82

253 D 0.93

254 M 0.93

255 L 0.97

256 E 0.97

257 N 0.97

258 Q 0.97

259 C 0.97

260 D 0.97

261 N 0.97

262 K 0.97

263 E 0.97

264 D 0.97

265 I 0.97

266 L 0.97

267 N 0.97

268 K 0.97

269 A 0.97

270 L 0.97

271 E 0.97

272 L 0.97

273 C 0.97 -

274 E 0.97

275 I 0.97

276 L 0.97

277 A 0.97

278 K 0.97

279 E 0.97

280 K 0.97

281 D 0.97

282 T 0.97

283 I 0.86

284 R 0.70

285 K 0.70 286 E 0 . 70

287 Y 0 .70 total: 39 residues

Final Results (k = 9/23) :

78.3 %: nuclear

8.7 % : mitochondrial

8.7 % : cytoplasmic

4.3 % : peroxisomal

» prediction for CG181662-01 is nuc (k=23)

A search of the NOV5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5D.

In a BLAST search of public sequence databases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5E.

PFam analysis predicts that the NOV5a-protein contains the domains shown in the Table 5F.

Example 6.

The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.

Table 6A. NOV6 Sequence Analysis

NOV6a, CG182223-01 SEQ ID NO: 71 4683 bp DNA Sequence ORF Start: ATG at 7 ORF Stop: TAA at 4588

GTCAAAATGAGTCTGCTGATGTTTACACAACTACTGCTCTGTGGATTTTTATATGTTCGGGTTGATGG

ATCGCGTCTTCGCCAGGAGGACTTTCCCCCGCGGATTGTGGAGCATCCTTCCGATGTCATCGTCTCTA AGGGCGAGCCCACGACTCTGAACTGCAAGGCGGAGGGCCGGCCAACGCCCACCATTGAGTGGTACAAA GATGGGGAGCGAGTGGAGACTGACAAGGACGATCCCCGGTCCCACAGGATGCTTCTGCCCAGCGGATC CTTATTCTTCTTGCGCATCGTGCACGGGCGCAGGAGTAAACCTGATGAAGGAAGCTACGTTTGTGTTG CGAGGAACTATCTTGGTGAAGCAGTGAGTCGAAATGCGTCTCTGGAAGTGGCATTGTTACGAGATGAC TTCCGACAAAACCCCACAGATGTTGTAGTGGCAGCTGGAGAGCCTGCAATCCTGGAGTGCCAGCCTCC CCGGGGACACCCAGAACCCACCATCTACTGGAAAAAAGACAAAGTTCGAATTGATGACAAGGAAGAAA GAATAAGTATCCGTGGTGGAAAACTGATGATCTCCAATACCAGGAAAAGTGATGCAGGGATGTATACT TGTGTTGGTACCAATATGGTGGGAGAAAGGGACAGTGACCCAGCAGAGCTGACTGTCTTTGAACGACC CACATTTCTCAGGAGGCCAATTAACCAGGTGGTACTGGAGGAAGAAGCTGTAGAATTTCGTTGTCAAG TCCAAGGAGATCCTCAACCAACTGTGAGGTGGAAAAAGGATGATGCAGACTTGCCAAGAGGAAGGTAT GACATCAAAGACGATTACACACTAAGAATTAAAAAGACCATGAGTACAGATGAAGGCACCTATATGTG TATTGCTGAGAATCGGGTTGGAAAAATGGAAGCCTCTGCTACACTCACCGTCCGAGCTCCCCCACAGT TTGTGGTTCGGCCAAGAGATCAGATTGTTGCTCAAGGTCGAACAGTGACATTTCCCTGTGAAACTAAA GGAAACCCACAGCCAGCTGTTTTTTGGCAGAAAGAAGGCAGCCAGAACCTACTTTTCCCAAACCAACC CCAGCAGCCCAACAGTAGATGCTCAGTGTCACCAACTGGAGACCTCACAATCACCAACATTCAACGTT CCGACGCGGGTTACTACATCTGCCAGGCTTTAACTGTGGCAGGAAGCATTTTAGCAAAAGCTCAACTG GAGGTTACTGATGTTTTGACAGATAGACCTCCACCTATAATTCTACAAGGCCCAGCCAACCAAACGCT GGCAGTGGATGGTACAGCGTTACTGAAATGTAAAGCCACTGGTGATCCTCTTCCTGTAATTAGCTGGT TAAAGGAGGGATTTACTTTTCCGGGTAGAGATCCAAGAGCAACAATTCAAGAGCAAGGCACACTGCAG ATTAAGAATTTACGGATTTCTGATACTGGCACTTATACTTGTGTGGCTACAAGTTCAAGTGGAGAGAC TTCCTGGAGTGCAGTGCTGGATGTGACAGAGTCTGGAGCAACAATCAGTAAAAACTATGATTTAAGTG ACCTGCCAGGGCCACCATCCAAACCGCAGGTCACTGATGTTACTAAGAACAGTGTCACCTTGTCCTGG CAGCCAGGTACCCCTGGAACCCTTCCAGCAAGTGCATATATCATTGAGGCTTTCAGCCAATCAGTGAG CAACAGCTGGCAGACCGTGGCAAACCATGTAAAGACCACCCTCTATACTGTAAGAGGACTGCGGCCCA ATACAATCTACTTATTCATGGTCAGAGCGATCAACCCCCAAGGTCTCAGTGACCCAAGTCCCATGTCA GATCCTGTGCGCACACAAGATATCAGCCCACCAGCACAAGGAGTGGACCACAGGCAAGTGCAGAAAGA GCTAGGAGATGTCCTTGTCCGTCTTCATAATCCAGTTGTGCTGACTCCCACCACGGTTCAGGTCACAT GGACGGTTGATCGCCAACCCCAGTTTATCCAAGGCTACCGAGTGATGTATCGTCAGACTTCAGGTCTG CAGGCGACATCTTCGTGGCAGAATTTAGATGCCAAAGTCCCGACTGAACGAAGTGCTGTCTTAGTCAA CCTGAAAAAGGGGGTGACTTATGAAATTAAAGTACGGCCATATTTTAATGAGTTCCAAGGAATGGATA GTGAATCTAAAACGGTTCGTACTACTGAAGAAGCCCCAAGTGCCCCACCACAGTCTGTCACTGTACTG ACAGTTGGAAGCTACAATAGCACAAGTATTAGTGTTTCCTGGGATCCTCCTCCTCCAGATCACCAGAA TGGAATTATCCAAGAATACAAGATCTGGTGTCTAGGAAATGAAACGCGATTCCATATCAACAAAACTG TGGATGCAGCCATTCGGTCCGTAATAATTGGTGGATTATTCCCAGGTATTCAATACCGGGTAGAGGTT GCAGCTAGTACCAGTGCAGGGGTTGGAGTAAAGAGTGAGCCACAGCCAATAATAATAGGGAGACGCAA TGAAGTTGTCATTACTGAAAACAATAACAGCATAACTGAGCAAATCACTGATGTGGTGAAGCAACCAG CCTTTATAGCTGGTATTGGTGGTGCCTGCTGGGTAATTCTGATGGGTTTTAGCATATGGTTGTATTGG CGAAGAAAGAAGAGGAAGGGACTCAGTAATTATGCTTTTTCTTTTTTCATAGTTACGTTTCAAAGAGG AGATGGAGGACTAATGAGCAATGGAAGCCGTCCAGGTCTTCTCAATGCTGGTGATCCCAGCTATCCAT GGCTTGCTGATTCTTGGCCAGCCACGAGCTTGCCAGTAAATAATAGCAACAGTGGCCCAAATGAGATT GGAAATTTTGGCCGTGGAGATGTGCTGCCACCAGTTCCAGGCCAAGGGGATAAAACAGCAACGATGCT CTCAGATGGAGCCATTTATAGTAGCATTGACTTCACTACCAAAACCAGTTACAACAGTTCCAGCCAAA TAACACAGGCTACCCCATATGCCACGACACAGATCTTGCATTCCAACAGCATACATGAATTGGCTGTC GATCTGCCTGATCCACAATGGAAAAGCTCAATTCAGCAAAAAACAGATCTGATGGGATTTGGTTATTC TCTACCTGATCAGAACAAAGGTAACAATTTACTTTACATTCCTGACTACCGATTGGCTGAGGGATTGT CTAATAGAATGCCACACAACCAGTCTCAGGATTTCAGCACCACCAGCTCTCACAACAGCTCAGAAAGG AGTGGCAGTCTTTCAGGTGGGAAAGGTGGAAAAAAGAAGAAAAATAAAAACTCTTCTAAACCACAGAA A2^CAATGGATCCACTTGGGCCAATGTCCCTCTACCTCCCCCCCCAGTCCAGCCCCTTCCTGGCACGG AGCTGGAACACTATGCAGTGGAACAACAAGAAAATGGGTATGACAGTGATAGCTGGTGCCCACCATTG CCAGTACAAACTTACTTACACCAAGGTCTGGAAGATGAACTGGAAGAAGATGATGATAGGGTCCCAAC ACCTCCTGTTCGAGGCGTGGCTTCTTCTCCTGCTATCTCCTTTGGACAGCAGTCCACTGCAACTCTTA CTCCATCCCCACGGGAAGAGATGCAACCCATGCTGCAGGCTCACCTGGATGAGTTGACAAGAGCCTAT CAGTTTGATATAGCAAAACAAACATGGCACATTCAAAGCAATAATCAACCTCCACAGCCTCCAGTTCC ACCGTTAGGTTATGTGTCTGGAGCCTTGATTTCTGATTTGGAAACGGATGTTGCAGATGATGATGCCG ACGACGAAGAGGAAGCTTTAGAAATCCCCAGGCCCCTGAGAGCACTGGACCAGACTCCTGGATCCAGC ATGGACAATCTAGACAGCTCTGTGACAGGTAACGGAAGACCTCGACCTACCAGCCCATTTTCTACTGA CAGTAACACCAGTGCAGCCCTGAGTCAAAGTCAGAGGCCTCGGCCCACTAAAAAACACAAGGGAGGGC GGATGGACCAACAACCAGCATTGCCTCATCGAAGGGAAGGAATGACAGATGATCTTCCACCACCACCA GATCCCCCGCCAGGTCAGGGTTTAAGGCAGCAAATAGGCCCGAGCCAGCAGGCTGGTAACGTGGAAAA CTCAGCAGAGAGAAAAGGAAGCTCTCTAGAGAGACAACATGCATCCAGCTTAGAAGACACAAAGAGCT CATTGGATTGTCCAGCTAGAACCTCCCTAGAGTGGCAGCGACAAACCCAGGAATGGATAAGCTCCACA GAACGACAAGAAGATATACGGAAAGCCCCACACAAACAAGGTTTTTCAGAGGAGGCCTTGGTGCCCTA TAGCAAGCCCAGTTTCCCATCTCCAGGTGGCCACAGCTCATCAGGAACAGCTTCTTCTAAGGGATCCA CTGGACCTAGGAAAACCGAGGTGTTGAGAGCAGGCCACCAGCGCAATGCCAGCGACCTTCTTGACATA GGATATATGGGCTCCAACAGTCAAGGACAGTTTACAGGTGAATTATGTAAGTGCTTAGGTCATTTAAA AGGCTATCGTGATTCAGAAAGAATCTTGGGTTAATAACATTGCCACATTAAACAAATTTCAGATTAAT AGAAAACTTGCTCTGTTACAAAAACAATCAATTGCAATTTTCAACAAGTTTGGTCATAA

NOV6a, CGI 82223-01 SEQ ID NO: 72 1527 aa MW at 167842.2kD Protein Sequence

MSLLMFTQLLLCGFLY VDGSRLRQEDFPPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDG ERVETDKDDPRSHRMLLPSGSLFFLRIVHGRRSKPDEGSYVCVARNYLGEAVSRNASLEVALLRDDFR QNPTDVWAAGEPAILECQPPRGHPEPTIY KKDKVRIDDKEERISIRGGKLMISN RKSDAGMYTCV GTNMVGERDSDPAEL VFERPTFLRRPINQWLEEEAVEFRCQVQGDPQP VR KKDDADLPRGRYDI KDDYTLRIl^TMSTDEGTYMCIAENRVGKMFASATLTVRAPPQFVVRPRDQIVAQGRTVTFPCETKGN PQPAVFWQKEGSQNLLFPNQPQQPNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAGSILAKAQLEV TDVLTDRPPPIILQGPANQTLAVDGTALL.KCKATGDPLPVIS LKΞGFTFPGRDPRATIQEQGTLQIK NLRISDTGTYTCVATSSSGETS SAVLDVTΞSGATISKNYDLSDLPGPPSKPQVTDVTKNSVTLSWQP GTPGTLPASAYIIEAFSQSVSNSWQ VAISTEΓVKTTIJYTVRGLRPNTIYLFMVRAINPQGLSDPSPMSDP VRTQDISPPAQGVDHRQVQKELGDVLVRLHNPVVLTPTTVQVTWTVDRQPQFIQGYRVMYRQTSGLQA TSS QNLDAKVPTERSAVLVNLKKGVTYEII^ PyFNEFQGIDSESKTVRTTEEAPSAPPQSVTVLTV GSYNSTSISVSVIDPPPPDHQNGIIQEYKI CLGNETRFHINKTVDAAIRSVIIGGLFPGIQYRVEVAA STSAGVGVKSEPQPIIIGRRNEWITENNNSITEQITDWKQPAFIAGIGGACWVILMGFSIWLYWRR KKRKGLSNYAFSFFIVTFQRGDGGMSNGSRPGLLNAGDPSYPWADSWPATS PVNNSNSGPNEIGN FGRGDVLPPVPGQGDKTATMLSDGAIYSSIDFTTKTSYNSSSQITQATPYATTQILHSNSIHELAVDL PDPQWKSSIQQKTDLMGFGYSLPDQNKGNNLLYIPDYRLAEGLSNRMPHNQSQDFSTTSSHNSSERSG S SGG GGKKKKNKNSSKPQKNNGSTWANVPLPPPPVQPLPGTELEHYAVEQQENGYDSDSWCPPLPV QTYLHQGLEDELEEDDDRVPTP VRGVASSPAISFGQQSTATLTPSPREΞMQPMLQAHLDΞLTRAYQF DIAKQTWHIQSNNQPPQPPVPPLGYVSGALISDLETDVADDDADDEEEALEIPRPLRALDQTPGSSMD NLDSSVTGNGRPRPTSPFSTDSN SAALSQSQRPRPTKHKGGRMDQQPA PHRREGMTDDLPPPPDP PPGQGLRQQIGPSQQAGNVENSAERKGSSLΞRQHASSLEDTKSSLDCPARTSLEWQRQTQEWTSSTΞR QEDIRKAPHKQGFSEEALVPYSKPSFPSPGGHSSSGTASSKGSTGPRKTEVLRAGHQRNASDLLDIGY MGSNSQGQFTGELCKCLGHLKGYRDSERILG

Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.

Table 6B. Protein Sequence Properties NOV6a

SignalP analysis: Cleavage site between residues 22 and 23

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 0; pos.chg 0; neg.chg 0 H-region: length 17; peak value 9.00 PSG score: 4.60

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.73 possible cleavage site: between 15 and 16

>» Seems to have no N-terminal signal peptide

ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1

Tentative number of TMS(s) for the threshold 0.5: 2 INTEGRAL Likelihood = -2.81 Transmembrane 1 - 17 INTEGRAL Likelihood = -3.98 Transmembrane 860 - 876 PERIPHERAL Likelihood = 1.01 (at 792) ALOM score: -3.98 (number of TMSs : 2)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 8 Charge difference: 0.0 C( 1.0) - N( 1.0) N >- C: N-terminal side will be inside

>» membrane topology: type 3a

MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75) : 4.50 Hyd Moment (95) : 2.47 G content: 1 D/E content: 1 S/T content: 2 Score: -4.61

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 28 VRV|DG

NUCDISC: discrimination of nuclear localization signals pat4: RRKK (5) at 883 pat4: RKKR (5) at 884 pat4: KKRK (5) at 885 pat4: KKKK (5) at 1097 pat4: KKHK (3) at 1330 pat7: PTVR KK (3) at 254 pat7: PTKKHKG (4) at 1328 bipartite: none content of basic residues: 10.3%

NLS Score: 1.57

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals : none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

COIL: Lupas' s algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23)

39.1 % : mitochondrial

34.8 %: nuclear

17.4 %: endoplasmic reticulum 4.3 % : cytoplasmic 4.3 %: peroxisomal

» prediction for CG182223-01 is mit (k=23)

A search of the NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6C.

In a BLAST search of public sequence databases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6D.

PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E.

Example 7.

The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A.

Table 7A. NOV7 Sequence Analysis

NOV7a, CGI 83585-01 SEQ ID NO: 73 1385 bp DNA Sequence [ORF Start: ATG at 145 JORF Stop: TAG at 1264

CTTGTATATATAATGGTAGACTGTAAAGGGTACCTTCCCCACCTGATATTCTGGAATGTCAGTTTGTA

GGTGGAGATTGCGACTTCTTTTTCCTTAGCAGAGCCAAGCTCCATTCAGCTGGTTACCACTTTGTGGG

TGTCTTTAATGAAGCTTATAAATGGCAGGAAGCAAACATTCCCGTGGTTTGGCATGGATATTGGTGGA

ACCCTGGTTAAGTTGGTTTACTTTGAACCGAAGGATATCACGGCAGAAGAAGAGCAGGAAGAAGTGGA GAACCTGAAGAGCATCCGGAAGTATTTGACTTCTAATACTGCTTATGGGAAAACTGGGATCCGAGACG TCCACCTGGAACTGAAAAACCTGACCATGTGTGGACGCAAAGGGAACCTGCACTTCATCCGCTTTCCC AGCTGTGCCATGCACAGGTTCATTCAGATGGGCAGCGAGAAGAACTTCTCTAGCCTTCACACCACCCT CTGTGCCACAGGAGGCGGGGCTTTCAAATTCGAAGAGGACTTCAGAATGATTGCTGACCTGCAGCTGC ATAAACTGGATGAACTGGACTGTCTGATTCAGGGCCTGCTTTATGTCGACTCTGTTGGCTTCAACGGC AAGCCAGAATGTTACTATTTTGAAAATCCCACAAATCCTGAATTGTGTCAAAAAAAGCCGTACTGCCT TGATAACCCATACCCTATGTTGCTGGTTAACATGGGCTCAGGTGTCAGCATTCTAGCCGTGTACTCCA AGGACAACTATAAAAGAGTTACAGGGACCAGTCTTGGAGGTGGAACATTCCTAGGCCTATGTTGCTTG CTGACTGGTTGTGAGACCTTTGAAGAAGCTCTGGAAATGGCAGCTAAAGGCGACAGCACCAATGTTGA TAAACTGGTGAAGGACATTTACGGAGGAGACTATGAACGATTTGGCCTTCAAGGATCTGCTGTAGCAT CAAGCTTGGGCAACATGATGAGTAAAGAAAAGCGAGATTCCATCAGCAAGGAAGACCTCGCCCGGGCC ACATTGGTCACCATCACCAACAACATTGGCTCCATTGCTCGGATGTGTGCGTTGAATGAGAACATAGA CAGAGTTGTGTTTGTTGGAAATTTTCTCAGAATCAATATGGTCTCCATGAAGCTGCTGGCATATGCCA TGGATTTTTGGTCCAAAGGACAACTGAAAGCTCTGTTTTTGGAACATGAGGGTTATTTTGGAGCCGTT GGGGCACTGTTGGAACTGTTCAAAATGACTGATGATAAGTAGAGACGAGCAGTGGAGGAAACAGCCTC CCAAAAGGACAGAGAACTAAAAAATTGCTGCTGGAGAAGGTGAAAGTCGCTTTGGGACGGAAGCCAAG

CCATTATGGCAGATGAACCTGCTGG

NOV7a, CG183585-01 SEQ ID NO: 74 373 aa MW at 41664.6kD Protein Sequence

MKLINGRKQTFP FGMDIGGTLVKLVYFEPKDITAEEEQEΞVENLKSIRKYLTSNTAYGKTGIRDVHL ELKNLTMCGRKGNIiHFIRFPSCA HRFIQMGSEKNFSSLHTTLCATGGGAFKFEEDFRMIADLQLHKL DELDCLIQGLLYVDSVGFNGKPECYYFENPTNPELCQKKPYCLDNPYPMLLVNMGSGVSILAVYSKDN YKRVTGTSLGGGTFLGLCCLLTGCETFEEALEMAAKGDSTNVDKLVKDIYGGDYERFGLQGSAVASSL GNM SKEKPJDSIS EDLARATLVTITNNIGSIARMCAI.NENIDRVVFVGNFLRIN1WSMKLLAYAMDF SKGQLKALFLEHEGYFGAVGALLELFKMTDDK

Further analysis of the NOV7a protein yielded the following properties shown in Table 7B.

Table 7B. Protein Sequence Properties NOV7a

SignalP analysis: No Known Signal Sequence Predicted

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region : length 8 ; pos . chg 3; neg . chg 0 H-region : length 8; peak value 5.54 PSG score : 1. 14

GvH : von Heijne ' s method for signal seq. recognition GvH score (threshold: -2.1): -10.98 possible cleavage site: between 59 and 60

»> Seems to have no N-terminal signal peptide

Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 0.95 (at 212) ALOM score: 0.42 (number of TMSs: 0)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 6 Charge difference: -2.0 C( 1.0) - N( 3.0) N >= C: N-terminal side will be inside

MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 10.35 Hyd Moment (95) : 1.52 G content: 2 D/E content: 1 S/T content: 1 Score: -4.69

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 17 GRKIQT

NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 11.3% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals: none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none

COIL: Lupas 's algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23)

60.9 %: cytoplasmic

21.7 %: nuclear

17 .4 % : mitochondrial

» prediction for CG183585-01 is cyt (k=23)

A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7C.

In a BLAST search of public sequence databases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7D.

PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7E.

Table 7E. Domain Analysis of NO 7a

Identities/

Pfam Domain NOV7a Match Region j Similarities Expect Value for the Matched Region

Fumble 12..367 196/401 (49%) 2.3e-234 346/401 (86%) Example 8.

The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.

Table 8A. NOV8 Sequence Analysis

NOV8a, CGI 83860-01 SEQ ID NO: 75 1858 bp DNA Sequence ORF Start: ATG at 72 ORF Stop: TGA at 786

CAGGTAGCCCGGCTCAGCCCTTCGCTTTCCAGCTGCGTCCTGCTCCCGGCCGCCCAGGGAGCCCAGTG

GCGATGAGGGCACTGCTGGCGCTTTGCCTTCTCCTTGGCTGGCTGCGCTGGGGCCCGGCGGGCGCCCA GCAGTCCGGAGAGTACTGCCACGGCTGGGTGGACGTGCAGGGCAACTACCACGAGGGCTTCCAGTGCC CAGAGGACTTCGACACGCTGGACGCTACCATCTGCTGCGGCTCCTGCGCGCTCCGCTACTGTTGCGCC GCGGTCGACGCCAGGCTGGAGCAGGGCGGCTGCACCAACGACCGCCGCGAACTGGAGCACCCAGGCAT CACTGCGCAGCCTGTCTACGTCCCCTTTCTCATCGTCGGCTCCATCTTCATTGCGTTCATCATCCTGG GCTCTGTAGTGGCTATTTATTGTTGCACCTGTTTGAGACCCAAGGAGCCCTCGCAGCAGCCAATCCGC TTCTCACTCCGCAGCTATCAGACAGAGACCCTGCCCATGATCCTGACCTCCACCAGCCCCAGGGCACC CTCCCGGCAGTCCAGCACAGCCACGAGCTCCAGCTCCACAGGCGGCTCCATCCGCAGGTTCTCCTTTG CCAGGGCTGAGCCGGGCTGCCTGGTGCCCTCACCGCCCCCGCCATACACCACCAGCCACTCAATCCAC CTGGCTCAGCCATCTGGTTTCCTGGTGTCACCCCAGTATTTCGCTTACCCCCTCCAGCAGGAGCCCCC ACTGCCTGGGAAGAGCTGTCCAGACTTCAGTTCCAGTTGACACGCCCAGGCCATGAATCCACAACTCA GTCAGATGGCAGACAGGTGGAGCCCTGCTCCCATTGCCACATGCAATTCTGAGAAAATTTCCCTTGTA

ACTGATCAGTGTCATGGAGGAGCATGCTAGGAAAACACAGCACCTTCTAATTTGAAAGTTCCTGTCTC

CAATCACAGAAAGGCTAAACCAGAGAACTGTTTTCTGGTTTTGCAAACATGTGATCATTACATTTCAA

TCTATGCTACTTTTATTCAAAATATGCAGCAGTTTGACTTTAAAGTTGCAAACTGGCTAAAAACGTTT

TACTGGACATTCAGCTATATTGCTTAGAAAAGGGCTACATGTTTCTTTTTCATATAAGTTGTTCATTG

AGTTATGATAGGAATATATTCATAAATAAGCAAAGAAAAATACCTAATTGTAATTATCAAAGGTTCAC

TTAAAAAAATTAACTATTAGGTAAACTTAAGGGGGCAGTGAAAAATCTATTTATGATTTCGGGAGTAA

CCTAACCATGAATAATATTAGCATAATGAGAACATTTACTTTTTAAATAAATAACTAAATTTTGTTTA

CAATATGAGTTTTTCCAGAATACAAGGTTTCAATAATCACATGAGGAGTTTAAAGTTTTAAATATATA

CTGAGACATTCATTGTAACACAGAGTGTATGTAAAATCATTTCCCCCACTCACTGGAGGGAGTATTTA

TTGCAGACTTTTTGTTCAGCAACATTTAGTGTTTCAGTGAAAGTTGGACAGTTGGGGCTTAAAACATT

TATTTGTAAAATGAGCTATGTTCAAATGTAAATATTTGTAATTTAATGTATTTACCACATTGACTGTA

CTAATTATTTAGTAGTCATACTGTAATTTTTATGTTAATAATAACTGGAGTTCAAAGTCTAGCTATTG

GTATAATCATCTAATATTATATATATCTCCAGTGCCCCTGAATTTTATGTTTGATGACTATATATTTG

GGCATATATCTTGTTGGATTAGAATAAATAAAACACTTTATATTTTCATGAACTCTAAAAAAAAAAAA

AAAAAAAAAAAAAAAAAAAGGG

NO V8a, CGI 83860-01 SEQ ID NO: 76 238 aa MW at 25860. lkD Protein Sequence

MRALLALCLLLGWLR GPAGAQQSGEYCHG VDVQGNYHEGFQCPEDFDTLDATICCGSCALRYCCAA VDARLEQGGCTNDRRELEHPGITAQPVYVPFLIVGSIFIAFIILGSWAIYCCTCLRPKEPSQQPIRF SLRSYQTETLPMILTSTSPRAPSRQSSTATSSSSTGGSIRRFSFARAEPGCLVPSPPPPYTTSHSIHL AQPSGFLVSPQYFAYPLQQEPPLPGKSCPDFSSS

Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.

Table 8 . Protein Sequence Properties NOV8a

SignalP analysis: Cleavage site between residues 22 and 23

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 2; pos.chg 1; neg.chg 0 H-region: length 12; peak value 10.66 PSG score: 6.26

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 1.27 possible cleavage site: between 21 and 22

>» Seems to have a cleavable signal peptide (1 to 21)

ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 22

Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1

INTEGRAL ' Likelihood =-11.04 Transmembrane 100 - 116 PERIPHERAL Likelihood = 1.27 (at 53) ALOM score: -11.04 (number of TMSs: 1)

MTOP: Prediction of membrane topology (Hart ann et al.) Center position for calculation: 10 Charge difference: -1.5 C( 0.5) - N( 2.0) N >= C: N-terminal side will be inside

>» membrane topology: type la (cytoplasmic tail 117 to 238)

MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 6.25 Hyd Moment (95) : 8.60 G content: 4 D/E content: 1 S/T content: 1 Score: -4.46

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 25 LR |GP

NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 6.7% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals:

XXRR-like motif in the N-terminus: RALL none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: too long tail

NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 89

COIL: Lupas 's algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23)

44.4 %: extracellular, including cell wall

22.2 %: Golgi

22.2 %: endoplas ic reticulum

11.1 %: plasma membrane

» prediction for CG183860-01 is exc (k=9)

A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8C.

In a BLAST search of public sequence databases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8D.

Example 9.

The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A.

Table 9A. NOV9 Sequence Analysis

NOV9a, CG184416-01 SEQ ID NO: 77 1321 bp DNA Sequence ORF Start: ATG at 39 ORF Stop: TGA at 1284

CTGCCCCATGCAGCCCTGAGCCCCACAGCAAGTCTGCCATGGGCCGCGGGGCCCGTGTCCCCTCGGAG

GCCCCGGGGGCAGGCGTCGAGCGCCGCTGGCTTGGAGCCGCGCTGGTCGCCCTGTGCCTCCTCCCCGC GCTGGTGCTGCTGGCCCGGCTGGGGGCCCCGGCGGTGCCGGCCTGGAGCGCAGCGCAGGGAGACGTCG CTGCGCTGGGCCTCTCGGCGGTCCCCCCCACCCGGGTCCCGGGCCCACTGGCCCCCCGCAGACGCCGC TACACGCTGACTCCAGCCAGGCTGCGCTGGGACCACTTCAACCTCACCTACAGGATCCTCTCCTTCCC GCGGAACCTGCTGAGCCCGCGGGAGACGCGGCGGGCCCTAGCTGCCGCCTTCCGCATGTGGAGCGACG TGTCCCCCTTCAGCTTCCGCGAGGTGGCCCCCGAGCAGCCCAGCGACCTCCGGATAGGCTTCTACCCG ATCAACCACACGGACTGCCTGGTCTCCGCGCTGCACCACTGCTTCGACGGCCCCACGGGGGAGCTGGC CCACGCCTTCTTCCCCCCGCACGGCGGCATCCACTTCGACGACAGCGAGTACTGGGTCCTGGGCCCCA CGCGCTACAGCTGGAAGAAAGGCGTGTGGCTCACGGACCTGGTGCACGTGGCGGCCCACGAGATCGGC CACGCGCTGGGCCTGATGCACTCACAACACGGCCGGGCGCTCATGCACCTGAACGCCACGCTGCGCGG CTGGAAGGCGTTGTCCCAGGACGAGCTGTGGGGGCTGCACCGGCTCTACGGTGAGTCCCTTTGTCGGG CGGGAGGGCGGGGACCGGGCGGTCCTGAGCCAGGCGTGCTCCCCACGCTCCCGATAGGATGCCTCGAC AGGCTGTTCGTGTGCGCGTCCTGGGCGCGGAGGGGCTTCTGCGACGCTCGCCGGCGGCTCATGAAGAG GCTCTGCCCCAGCAGCTGCGACTTCTGCTACGAATTCCCCTTCCCCACGGTGGCCACCACCCCACCGC CCCCCAGGACCAAAACCAGGCTGGTGCCCGAGGGCAGGAACGTGACCTTCCGCTGCGGCCAGAAGATC CTCCACAAGAAAGGGAAAGTGTACTGGTACAAGGACCAGGAGCCCCTGGAGTTCTCCTACCCCGGCTA CCTGGCCCTGGGCGAGGCGCACCTGAGCATCATCGCCAACGCCGTCAATGAGGGCACCTACACCTGCG TGGTGCGCCGCCAGCAGCGCGTGCTGACCACCTACTCCTGGCGAGTCCGTGTGCGGGGCTGAGCCCGG CTGATAAAGCACTTTCTCTCTGAAAAAAA

NOV9a, CGI 84416-01 SEQ ID NO: 78 415 aa MW at 46304.0kD Protein Sequence

MGRGARVPSEAPGAGVERR LGAALVALCLLPALVLLARLGAPAVPA SAAQGDVAALGLSAVPPTRV PGPLAPRRRRYTLTPARLR DHFNLTYRILSFPRNLLSPRETRRALAAAFRM SDVSPFSFREVAPEQ PSDLRIGFYPINHTDCLVSALHHCFDGPTGELAHAFFPPHGGIHFDDSEY VLGPTRYSWKKGVWLTD LVHVAAHEIGHALGLMHSQHGRALMHLNATLRGWKALSQDEL GLHRLYGESLCRAGGRGPGGPΞPGV LPTLPIGCLDRLFVCAS ARRGFCDARRRLMKRLCPSSCDFCYEFPFPTVATTPPPPRTKTRLVPΞGR NVTFRCGQKILHKKGKVYWYKDQEPLEFSYPGYLALGEAHLSIIANAVNEGTYTCWRRQQRVLTTYS WRVRVRG

Further analysis ofthe NOV9aprotein yielded the followingproperties shown in Table 9B.

Table 9B. Protein Sequence Properties NO 9a

SignalP analysis: I Cleavage site between residues 45 and 46

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 10; pos.chg 2; neg.chg 1 H-region: length 6; peak value -6.74 PSG score: -11.14

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 1.31 possible cleavage site: between 37 and 38

»> Seems to have no N-terminal signal peptide

INTEGRAL Likelihood =-10.40 Transmembrane 21 - 37 PERIPHERAL Likelihood = 0.79 (at 272) ALOM score: -10.40 (number of TMSs: 1)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 28 Charge difference: 0.0 C( 1.0) - N( 1.0) N >= C: N-terminal side will be inside

>» membrane topology: type 2 (cytoplasmic tail 1 to 21)

MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment (75): 4.37 Hyd Moment (95): 11.61 G content: 4 D/E content: 2 S/T content: 1 Score: -6.42

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 16 ARV|PS NUCDISC: discrimination of nuclear localization signals pat4: PRRR (4) at 74 pat4: RRRR (5) at 75 pat7: PLAPRRR (3) at 71 pat7: PRRRRYT (5) at 74 bipartite: RRQQRVLTTYS RVRVR at 398 content of basic residues: 12.8% NLS Score: 1.27

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals:

XXRR-like motif in the N-terminus: GRGA none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2 : 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: found TLPI at 275

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23) :

39.1 % : mitochondrial 30.4 % : cytoplasmic

8.7 % : vacuolar

8.7 % : endoplasmic reticulum

4.3 %: Golgi

4.3 %: vesicles of secretory system

4.3 % : nuclear

» prediction for CG184416-01 is mit (k=23)

A search of the NOV9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 9C.

In a BLAST search of public sequence databases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9D.

PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E.

Example 10.

The NOV10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10A.

Table 10A. NO 10 Sequence Analysis

NOV10a, CG185200-01 SEQ ID NO: 79 2050 bp DNA Sequence ORF Start: ATG at 66 ORF Stop: TAA at 918

AGCACCATTTAAAGCCACTGGGAAATTTGTTGTCTAGTGGTTGTGGGTGAATAAAGGAGGGCAGAATG

GATGATTTCATCTCCATTAGCCTGCTGTCTCTGGCTΑTGTTGGTGGGATGTTACGTGGCCGGAATCAT TCCCTTGGCTGTTAATTTCTCAGAGGAACGACTGAAGCTGGTGACTGTTTTGGGTGCTGGCCTTCTCT GTGGAACTGCTCTGGCAGTCATCGTGCCTGAAGGAGTACATGCCCTTTATGAAGATATTCTTGAGGGA AAACACCACCAAGCAAGTGAAACACATAATGTGATTGCATCAGACAAAGCAGCAGAAAAATCAGTTGT CCATGAACATGAGCACAGCCACGACCACACACAGCTGCATGCCTATATTGGTGTTTCCCTCGTTCTGG GCTTCGTTTTCATGTTGCTGGTGGACCAGATTGGTAACTCCCATGTGCATTCTACTGACGCTGATGGT GTTGCTTTGGGAGCAGCAGCATCTACTTCACAGACCAGTGTCCAGTTAATTGTGTTTGTGGCAATCAT GCTACATAAGGCACCAGCTGCTTTTGGACTGGTTTCCTTCTTGATGCATGCTGGCTTAGAGCGGAATC GAATCAGAAAGCACTTGCTGGTCTTTGCATTGGCAGCACCAGTTACGTCCATGGTGACATACTTAGGA CTGAGTAAGAGCAGTAAAGAAGCCCTTTCAGAGGTGAACGCCACGGGAGTGGCCATGCTTTTCTCTGC CGGGACATTTCTTTATGTTGCCACAGTACATGTCCTCCCTGAGGTGGGCGGAATAGGGCACAGCCACA AGCCCGATGCCACGGGAGGGAGAGGCCTCAGCCGCCTGGAAGTGGCAGCCCTGGTTCTGGGTTGCCTC ATCCCTCTCATCCTGTCAGTAGGACACCAGCATTAAATGTTCAAGGTCCAGCCTTGGTCCAGGGCCGT TTGCCATCCAGTGAGAACAGCCGGCACGTGACAGCTACTCACTTCCTCAGTCTCTTGTCTCACCTTGC

GCATCTCTACATGTATTCCTAGAGTCCAGAGGGGAGGTGAGGTTAAAACCTGAGTAATGGAAAAGCTT

TTAGAGTAGAAACACATTTACGTTGCAGTTAGCTATAGACATCCCATTGTGTTATCTTTTAAAAGGCC

CTTGACATTTTGCGTTTTAATATTTCTCTTAACCCTATTCTCAGGGAAGATGGAATTTAGTTTTAAGG

IAAAAGAGGAGAACTTCATACTCACAATGAAATAGTGATTATGAAAATACAGTGTTCTGTAATTAAGCT

ATGTCTCTTTCTTCTTAGTTTAGAGGCTCTGCTACTTTATCCATTGATTTTTAACATGGTTCCCACCA

TGTAAGACTGGTGCTTTAGCATCTATGCCACATGCGTTGATGGAAGGTCATAGCACCCACTCACTTAG

1ATGCTAAAGGTGATTCTAGTTAATCTGGGATTAGGGTCAGGAAAATGATAGCAAGACACATTGAAAGC

TCTCTTTATACTCAAAAGAGATATCCATTGAAAAGGGATGTCTAGAGGGATTTAAACAGCTCCTTTGG

CACGTGCCTCTCTGAATCCAGCCTGCCATTCCATCAAATGGAGCAGGAGAGGTGGGAGGAGCTTCTAA

AGAGGTGACTGGTATTTTGTAGCATTCCTTGTCAAGTTCTCCTTTGCAGAATACCTGTCTCCACATTC

CTAGAGAGGAGCCAAGTTCTAGTAGTTTCAGTTCTAGGCTTTCCTTCAAGAACAGTCAGATCACAAAG

TGTCTTTGGAAATTAAGGGATATTAAATTTTAAGTGATTTTTGGATGGTTATTGATATCTTTGTAGTA

GCTTTTTTTAAAAGACTACCAAAATGTATGGTTGTCCTTTTTTTTTGTTTTTTTTTTTTTTAATTATT

TCTCTTAGCAGATCAGCAATCCCTCTAGGGACCTAAATACTAGGTCAGCTTTGGCGACACTGTGTCTT

CTCACATAACCACCTGTAGCAAGATGGATCATAAATGAGAAGTGTTTGCCTATTGATTTAAAGCTTAT

TGGAATCATG

NOVlOa, CG185200-01 SEQ ID NO: 80 j 284 aa MW at 29900.4kD Protein Sequence

M)DFISISLLSI-AMLVGCYVAGIIPLAVNFSEERLKLVTVLGAGLLCGTALAVIVPEGVHALYEDILE GKHHQASETHNVIASD AAE SWHEHEHSHDHTQLHAYIGVSLVLGFVPMLLVDQIGNSHVHSTDAD GVALGAAASTSQTSVQLIVPVAIMLHKΑPAAFGLVSFLMHAGLERNRIRKHLLVFALAAPVTSMVTYL GLSKSSK2ALSEVNATGVAMLFSAGTFLYVATVHVLPEVGGIGHSHKPDATGGRGLSRLEVAALVLGC LIPLILSVGHQH

NOVlOb, CGI 85200-02 SEQ ID NO: 81 1120 bp

|DNA Sequence foRp Start ATG at 94 |ORF Stop: TAA at 1015

GGAACCACCACACCTGTTTAAAGAACCTAAGCACCATTTAAAGCCACTGGAAATTTGTTGTCTAGTGG

TTGTGGGTGAATAAAGGAGGGCAGAATGGATGATTTCATCTCCATTAGCCTGCTGTCTCTGGCTATGT

TGGTGGGATGTTACGTGGCCGGAATCATTCCCTTGGCTGTTAATTTCTCAGAGGAACGACTGAAGCTG GTGACTGTTTTGGGTGCTGGCCTTCTCTGTGGAACTGCTCTGGCAGTCATCGTGCCTGAAGGAGTACA TGCCCTTTATGAAGATATTCTTGAGGGAAAACACCACCAAGCAAGTGAAACACATAATGTGATTGCAT CAGACAAAGCAGCAGAAAAATCAGTTGTCCATGAACATGAGCACAGCCACGACCACACACAGCTGCAT GCCTATATTGGTGTTTCCCTCGTTCTGGGCTTCGTTTTCATGTTGCTGGTGGACCAGATTGGTAACTC CCATGTGCATTCTACTGACGATCCAGAAGCAGCAAGGTCTAGCAATTCCAAAATCACCACCACGCTGG GTCTGGTTGTCCATGCTGCAGCTGATGGTGTTGCTTTGGGAGCAGCAGCATCTACTTCACAGACCAGT GTCCAGTTAATTGTGTTTGTGGCAATCATGCTACATAAGGCACCAGCTGCTTTTGGACTGGTTTCCTT CTTGATGCATGCTGGCTTAGAGCGGAATCGAATCAGAAAGCACTTGCTGGTCTTTGCATTGGCAGCAC CAGTTATGTCCATGGTGACATACTTAGGACTGAGTAAGAGCAGTAAAGAAGCCCTTTCAGAGGTGAAC GCCACGGGAGTGGCCATGCTTTTCTCTGCCGGGACATTTCTTTATGTTGCCACAGTACATGTCCTCCC TGAGGTGGGCGGAATAGGGCACAGCCACAAGCCCGATGCCGCGGGAGGGAGAGGCCTCAGCCGCCTGG AAGTGGCAGCCCTGGTTCTGGGTTGCCTCATCCCTCTCATCCTGTCAGTAGGACACCAGCATTAAATG TTCAAGGTCCAGCCTTGGTCCAGGGCCGTTTGCCATCCAGTGAGAACAGCCGGCACGTGACAGCTACT

CACTTCCTCAGTCTCTTGTCTCACCTAAGGCG

NOV1 Ob, CGI 85200-02 SEQ ID NO: 82 307 aa MW at 32221. OkD Protein Sequence

MDDFISISLLSLAI^VGCYVAGIIPLAVNFSEERLKLVTVLGAGLLCGTALAVIVPEGVHALYEDILΞ GKHHQASETHNVIASDKAAEKSVVHEHEHSHDHTQLHAYIGVSLVLGFVFMLLVDQIGNSHVHSTDDP EAARSSNSKITTTLGLVVHAAADGVALGAAASTSQTSVQLIVFVAIMLHKAPAAFGLVSFLMHAGLER NRIRKHLLVFALAAPVMS VTYLGLSKSSKEALSEVNATGVAMLFSAGTFLYVATVHVLPEVGGIGHS HKPDAAGGRGLSRLEVAALVLGCLIPLILSVGHQH

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 10B.

Table 10B. Comparison of the NOV10 protein sequences.

NOVlOa MDDFISISLLSLAMLVGCYVAGIIPLAVNFSEERLKLVTVLGAGLLCGTALAVIVPEGVH

NOVlOb MDDFISISLLSLAMLVGCYVAGIIPLAVNFSEERLKLVTVLGAGLLCGTALAVIVPEGVH

NOVlOa ALYEDILEGKHHQASETHNVIASDKAAEKSWHEHEHSHDHTQLHAYIGVSLVLGFVFML

NOVlOb ALYEDILEGKHHQASETHNVIASDKAAEKSWHEHEHSHDHTQLHAYIGVSLVLGFVFML

NOVlOa LVDQIGNSHVHSTD ADGVALGAAASTSQTSVQLIVFV

NOVlOb LVDQIGNSHVHSTDDPEAARSSNSKITTTLGLWHAAADGVALGAAASTSQTSVQLIVFV

NOVlOa AIMLHKAPAAFGLVSFLMHAGLERNRIRKHLLVFALAAPVTSMVTYLGLSKSSKEALSEV

NOVlOb AIMLHKAPAAFGLVSFLMHAGLERNRIRKHLLVFALAAPVMSMVTYLGLSKSSKEALSEV

NOVlOa NATGVAMLFSAGTFLYVATVHVLPEVGGIGHSHKPDATGGRGLSRLEVAALVLGCLIPLI

NOV10b NATGVAMLFSAGTFLYVATVHVLPEVGGIGHSHKPDAAGGRGLSRLEVAALVLGCLIPLI

NOVlOa LSVGHQH

NOVlOb LSVGHQH

NOVlOa (SEQ ID NO: 80) NOVlOb (SEQ ID NO: 82)

Further analysis of the NOVlOa protein yielded the following properties shown in Table IOC.

Table IOC. Protein Sequence Properties NOVlOa

SignalP analysis: Cleavage site between residues 62 and 63

PSORT II analysis: PSG: a new signal peptide prediction method

N-region: length 3; pos.chg 0; neg.chg 2 H-region: length 28; peak value 0.00 PSG score: -4.40

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -1.40 possible cleavage site: between 52 and 53

>» Seems to have no N-terminal signal peptide

ALOM: Klein et al's method for TM region allocation

Init position for calculation: 1

Tentative number of TMS(s) for the threshold 0.5: 7

INTEGRAL Likelihood = -6.48 Transmembrane 12 - 28

INTEGRAL Likelihood = -5.68 Transmembrane 38 - 54

INTEGRAL Likelihood = -8.49 Transmembrane 106 - 122

INTEGRAL Likelihood = -1.97 Transmembrane 153 - 169

INTEGRAL Likelihood = -3.13 Transmembrane 188 - 204

INTEGRAL Likelihood = -1.01 Transmembrane 221 - 237

INTEGRAL Likelihood = -8.81 Transmembrane 265 - 281

PERIPHERAL Likelihood = 9.18 (at 135)

ALOM score: -8.81 (number of TMSs : 7)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 19 Charge difference: 1.0 C( 0.0) - N(-1.0) C > N: C-terminal side will be inside

>» membrane topology: type 3b

MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 8.48 Hyd Moment ( 95) : 7.98 G content : 0 D/E content: 2 S/T content: 0 Score: -6.50

NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite : none content of basic residues: 5.3% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals : none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2 : 2nd peroxisomal targeting signal : none

VAC: possible vacuolar targeting motif: none RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23) :

55.6 : endoplasmic reticulum

11.1 %: Golgi

11.1 %: vacuolar

11.1 %: vesicles of secretory system

11.1 %: mitochondrial

» prediction for CG185200-01 is end (k=9)

A search of the NOVlOa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10D.

In a BLAST search of public sequence databases, the NOVlOa protein was found to have homology to the proteins shown in the BLASTP data in Table 10E.

PFam analysis predicts that the NOVlOa protein contains the domains shown in the Table 10F.

Table 10F. Domain Analysis of NOVlOa

Identities/

Pfam Domain NOVlOa Match Region Similarities Expect Value for the Matched Region

Zip 4..279 78/407 (19%) 2.1e-34 214/407 (53%)

Example 11.

The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11 A.

Table 11 A. NOV11 Sequence Analysis

NOVlla, CG50513-01 SEQ ID NO: 83 1598 bp DNA Sequence ORF Start: at 1 JORF Stop: TGA at 1354

AAACAGCCACTTGTTTCATCCCACCTGGGCATTAGGTTGACTTCAAAGATGCCTCAGTTACTGCAAAA CATTAATGGGATCATCGAGGCCTTCAGGCGCTATGCAAGGACGGAGGGCAACTGCACAGCGCTCACeC GAGGGGAGCTGAAAAGACTCTTGGAGCAAGAGTTTGCCGATGTGATTGTGAAACCCCACGATCCAGCA ACTGTGGATGAGGTCCTGCGTCTGCTGGATGAAGACCACACAGGGACTGTGGAATTCAAGGAATTCCT GGTCTTAGTGTTTAAAGTTGCCCAGGCCTGTTTCAAGACACTGAGCGAGAGTGCTGAGGGAGCCTGCG GCTCTCAAGAGTCTGGAAGCCTCCACTCTGGGGCCTCGCAGGAGCTGGGCGAAGGACAGAGAAGTGGC ACTGAAGTGGGAAGGGCGGGGAAAGGGCAGCATTATGAGGGGAGCAGCCACAGACAGAGCCAGCAGGG TTCCAGAGGGCAGAACAGGCCTGGGGTTCAGACCCAGGGTCAGGCCACTGGCTCTGCGTGGGTCAGCA GCTATGACAGGCAAGCTGAGTCCCAGAGCCAGGAAAGAATAAGCCCGCAGATACAACTCTCTGGGCAG ACAGAGCAGACCCAGAAAGCTGGAGAAGGCAAGAGGAATCAGACAACAGAGATGAGGCCAGAGAGACA GCCACAGACCAGGGAACAGGACAGAGCCCACCAGACAGGTGAGACTGTGACTGGATCTGGAACTCAGA CCCAGGCAGGTGCCACCCAGACTGTGGAGCAGGACAGCAGCCACCAGACAGGAAGCACCAGCACCCAG ACACAGGAGTCCACCAATGGCCAGAACAGAGGGACTGAGATCCACGGTCAAGGCAGGAGCCAGACCAG CCAGGCTGTGACAGGAGGACACACTCAGATACAGGCAGGGTCACACACCGAGACTGTGGAGCAGGACA GAAGCCAAACTGTAAGCCACGGAGGGGCTAGAGAACAGGGACAGACCCAGACGCAGCCAGGCAGTGGT CAAAGATGGATGCAAGTGAGCAACCCTGAGGCAGGAGAGACAGTACCGGGAGGACAGGCCCAGACTGG GGCAAGCACTGAGTCAGGAAGGCAGGAGTGGAGCAGCACTCACCCAAGGCGCTGTGTGACAGAAGGGC AGGGAGACAGACAGCCCACAGTGGTTGGTGAGGAATGGGTTGATGACCACTCAAGGGAGACAGTGATC CTCAGGCTGGACCAGGGCAACTTGCATACCAGTGTTTCCTCAGCACAGGGCCAGGATGCAGCCCAGTC AGAAGAGAAGCGAGGCATCACAGCTAGAGAGCTGTATTCCTACTTGAGAAGCACCAAGCCATGACTTC CCCGACTCCAATGTCCAGTACTGGAAGAAGACAGCTGGAGAGAGTTTGGCTTGTCCTGCATGGCCAAT

CCAGTGGGTGCATCCCTGGACATCAGCTCTTCATTATGCAGCTTCCCTTTTAGGTCTTTCTCAATGAG jATAATTTCTGCAAGGAGCTTTCTATCCTGAACTCTTCTTTCTTACCTGCTTTGCGGTGCAGACCCTCT

CAGGAGCAGGAAGACTCAGAACAAGTCACCCCTT

NOV1 la, CG50513-01 SEQ ID NO: 84 451 aa MW at 48908.6kD Protein Sequence

KQPLVSSHLGIRLTS MPQLLQNINGIIEAFRRYARTEGNCTALTRGELKRLLEQEFADVIVKPHDPA TVDEVLRLLDEDHTGTVEFKEFLVLVFKVAQACFKTLSESAEGACGSQESGSLHSGASQELGEGQRSG TEVGRAGKGQHYEGSSHRQSQQGSRGQNRPGVQTQGQATGSA VSSYDRQAESQSQERISPQIQLSGQ TEQTQKAGEGK^QTTEMRPERQPQTREQDRAHQTGEWTGSGTQTQAGATQTVEQDSSHQTGSTSTQ TQESTNGQNRGTEIHGQGRSQTSQAVTGGHTQIQAGSHTETVEQDRSQTVSHGGAREQGQTQTQPGSG QRWMQVSNPEAGETVPGGQAQTGASTESGRQEWSSTHPRRWTEGQGDRQPTWGEEWVDDHSRETVI LRLDQGNLHTSVSSAQGQDAAQSEEKRGITARELYSYLRSTKP

NOV1 lb, 273654175 SEQ ID NO: 85 151 bp

DNA Sequence RF Start: at 2 JORF Stop: at End of Sequence

ACCGGATCCTTACTGCAAAACATTAATGGGATCATCGAGGCCTTCAGGCGCTATGCAAGGACGGAGG

GCAACTGCACAGCGCTCACCCGAGGGGAGCTGAAAAGACTCTTGGAGCAAGAGTTTGCCGATGTGATT

GTGAAACTCGAGGGC

NOV1 lb, 273654175 SEQ ID NO: 86 50 aa MW at 5608.3kD Protein Sequence J

TGSLLQNINGIIEAFRRYARTEGNCTALTRGELKRLLEQEFADVIVKLEG

NOV1 lc, CG50513-02 SEQ ID NO: 87 1039 bp

DNA Sequence ORF Start: at 1 JORF Stop: end of sequence

GTCAATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCCATGAGCCAGGCCTGTAACACAGAGCC CTGTCCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTCAGCTACCTGTGGAGTTGGAATTCAGA CCCGAGATGTGTACTGCCTGCACCCAGGGGAGACCCCTGCCCCTCCTGAGGAGTGCCGAGATGAAAAG CCCCATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCTGGCTGGCACATTGAAGAATGGCAGCA GTGTTCCAGGACTTGTGGCGGGGGAACTCAGAACAGAAGAGTCACCTGTCGGCAGCTGCTAACGGATG GCAGCTTTTTGAATCTCTCAGATGAATTGTGCCAAGGACCCAAGGCATCGTCTCACAAGTCCTGTGCC AGGACAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCGAAGTGTTCTGTCAGTTGTGGTGTTGG AATCCAGAGAAGAAAGCAGGTGTGTCAAAGGCTGGCAGCCAAAGGTCGGCGCATCCCCCTCAGTGAGA TGATGTGCAGGGATCTACCAGGGTTCCCTCTTGTAAGATCTTGCCAGATGCCTGAGTGCAGTAAAATC AAATCAGAGATGAAGACAAAACTTGGTGAGCAGGGTCCGCAGATCCTCAGTGTCCAGAGAGTCTACAT TCAGACAAGGGAAGAGAAGCGTATTAACCTGACCATTGGTAGCAGAGCCTATTTGCTGCCCAACACAT CCGTGATTATTAAGTGCCCAGTGCGACGATTCCAGAAATCTCTGATCCAGTGGGAGAAGGATGGCCGT TGCCTGCAGAACTCCAAACGGCTTGGCATCACCAAGTCAGGCTCACTAAAAATCCACGGTCTTGCTGC CCCCGACATCGGCGTGTACCGGTGCATTGCAGGCTCTGCACAGGAAACAGGTGTGCTCAAGCTCATTG GTACTGACAACCGGCTCATTGCACGCCCAACCCTCANGGAGCCTATGAGGGAATATCCTGGGATGGAC CACAACGAAGCCAATAGTT

|NWΪ 1CTCG50513-02 JSEQ ID NO: 88 J346 aa JMW at 38248.6kD Protein Sequence

VNDSLCDMVHRPPAMSQACNTEPCPPR HVGS GPCSATCGVGIQTRDVYCLHPGETPAPPEECRDEK PHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQNRRVTCRQLLTDGSFLNLSDELCQGPKASSHKSCA RTDCPPHLAVGD SKCSVSCGVGIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKI KSEMKTKLGEQGPQILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWE DGR CLQNSKRLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETGVL LIGTDNRLIARPTLXEPMREYPGMD HNEANS

NOV1 Id, CG50513-03 JSEQ ID NO: 89 6303 bp

DNA Sequence ORF Start: ATG at 425 ORF Stop: TAA at 4268

TATAATTATTAATAGAGACCTTTCAAAGGACAAATTCTGTGAAATAAAGTGGTTTTCTGAAGAGCCTA

CTAATAGGACAGTGTGTTAATATCACTAATAAGAGAGTAATGATTATAAAAAGGAATAAATTTATTGA

AATTGCAAGATACTTTTCTCCTTTGATTAATATACTGCTAGTTTAGTTTTCTACATTTTCAAATAGAA

CTGGGGAATTTGTGTCGTAGATATTCTTGACAACTAAAGAGATGGTGGCTGAATTTTTGGGAATGGTT

GATAACACTTGATATTTTTAGTTTCCAATTTGGAAGAGCTCTGTCTCTTGGGATGTCAAATATTATAT

TCGTCAATTAATGAATGTGTTAATTTATTATAGAAATGATATTCTCACAATGATTTCATTTGTAGTGA

TGGATTTAAAGAGATAATGCCCTATGACCACTTCCAACCTCTTCCTCGCTGGGAACATAATCCTTGGA

CTGCATGTTCCGTGTCCTGTGGAGGAGGGATTCAGAGACGGAGCTTTGTGTGTGTAGAGGAATCCATG CATGGAGAGATATTGCAGGTGGAAGAATGGAAGTGCATGTACGCACCCAAACCCAAGGTTATGCAAAC TTGTAATCTGTTTGATTGCCCCAAGTGGATTGCCATGGAGTGGTCTCAGTGCACAGTGACTTGTGGCC GAGGGTTACGGTACCGGGTTGTTCTGTGTATTAACCACCGCGGAGAGCATGTTGGGGGCTGCAATCCA CAACTGAAGTTACACATCAAAGAAGAATGTGTCATTCCCATCCCGTGTTATAAACCAAAAGAAAAAAG TCCAGTGGAAGCAAAATTGCCTTGGCTGAAACAAGCACAAGAACTAGAAGAGACCAGAATAGCAACAG AAGAACCAACGTTCATTCCAGAACCCTGGTCAGCCTGCAGTACCACGTGTGGGCCGGGTGTGCAGGTC CGTGAGGTGAAGTGCCGTGTGCTCCTCACATTCACGCAGACTGAGACTGAGCTGCCCGAGGAAGAGTG TGAAGGCCCCAAGCTGCCCACCGAACGGCCCTGCCTCCTGGAAGCATGTGATGAGAGCCCGGCCTCCC GAGAGCTAGACATCCCTCTCCCTGAGGACAGTGAGACGACTTACGACTGGGAGTACGCTGGGTTCACC CCTTGCACAGCAACATGCGTGGGAGGCCATCAAGAAGCCATAGCAGTGTGCTTACATATCCAGACCCA GCAGACAGTCAATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCCATGAGCCAGGCCTGTAACA CAGAGCCCTGTCCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTCAGCTACCTGTGGAGTTGGA ATTCAGACCCGAGATGTGTACTGCCTGCACCCAGGGGAGACCCCTGCCCCTCCTGAGGAGTGCCGAGA TGAAAAGCCCCATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCTGGCTGGCACATTGAAGAAT GGCAGCAGTGTTCCAGGACTTGTGGCGGGGGAACTCAGAACAGAAGAGTCACCTGTCGGCAGCTGCTA ACGGATGGCAGCTTTTTGAATCTCTCAGATGAATTGTGCCAAGGACCCAAGGCATCGTCTCACAAGTC CTGTGCCAGGACAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCGAAGTGTTCTGTCAGTTGTG GTGTTGGAATCCAGAGAAGAAAGCAGGTGTGTCAAAGGCTGGCAGCCAAAGGTCGGCGCATCCCCCTC AGTGAGATGATGTGCAGGGATCTACCAGGGTTCCCTCTTGTAAGATCTTGCCAGATGCCTGAGTGCAG TAAAATCAAATCAGAGATGAAGACAAAACTTGGTGAGCAGGGTCCGCAGATCCTCAGTGTCCAGAGAG TCTACATTCAGACAAGGGAAGAGAAGCGTATTAACCTGACCATTGGTAGCAGAGCCTATTTGCTGCCC AACACATCCGTGATTATTAAGTGCCCCGTGCGACGATTCCAGAAATCTCTGATCCAGTGGGAGAAGGA TGGCCGTTGCCTGCAGAACTCCAAACGGCTTGGCATCACCAAGTCAGGCTCACTAAAAATCCACGGTC TTGCTGCCCCCGACATCGGCGTGTACCGGTGCATTGCAGGCTCTGCACAGGAAACAGTTGTGCTCAAG CTCATTGGTACTGACAACCGGCTCATCGCACGCCCAGCCCTCAGGGAGCCTATGAGGGAATATCCTGG GATGGACCACAGCGAAGCCAATAGTTTGGGAGTCACATGGCACAAAATGAGGCAAATGTGGAATAACA AAAATGACCTTTATCTGGATGATGACCACATTAGTAACCAGCCTTTCTTGAGAGCTCTGTTAGGCCAC TGCAGCAATTCTGCAGGAAGCACCAACTCCTGGGAGTTGAAGAATAAGCAGTTTGAAGCAGCAGTTAA ACAAGGAGCATATAGCATGGATACAGCCCAGTTTGATGAGCTGATAAGAAACATGAGTCAGCTCATGG AAACCGGAGAGGTCAGCGATGATCTTGCGTCCCAGCTGATATATCAGCTGGTGGCCGAATTAGCCAAG GCACAGCCAACACACATGCAGTGGCGGGGCATCCAGGAAGAGACACCTCCTGCTGCTCAGCTCAGAGG GGAAACAGGGAGTGTGTCCCAAAGCTCGCATGCAAAAAACTCAGGCAAGCTGACATTCAAGCCGAAAG GACCTGTTCTCATGAGGCAAAGCCAACCTCCCTCAATTTCATTTAATAAAACAATAAATTCCAGGATT GGAAATACAGTATACATTACAAAAAGGACAGAGGTCATCAATATACTGTGTGACCTTATTACCCCCAG TGAGGCCACATATACATGGACCAAGGATGGAACCTTGTTACAGCCCTCAGTAAAAATAATTTTGGATG GAACTGGGAAGATACAGATACAGAATCCTACAAGGAAAGAACAAGGCATATATGAATGTTCTGTAGCT AATCATCTTGGTTCAGATGTGGAAAGTTCTTCTGTGCTGTATGCAGAGGCACCTGTCATCTTGTCTGT TGAAAGAAATATCACCAAACCAGAGCACAACCATCTGTCTGTTGTGGTTGGAGGCATCGTGGAGGCAG CCCTTGGAGCAAACGTGACAATCCGATGTCCTGTAAAAGGTGTCCCTCAGCCTAATATAACTTGGTTG AAGAGAGGAGGATCTCTGAGTGGCAATGTTTCCTTGCTTTTCAATGGATCCCTGTTGTTGCAGAATGT TTCCCTTGAAAATGAAGGAACCTACGTCTGCATAGCCACCAATGCTCTTGGAAAGGCAGTGGCAACAT CTGTACTCCACTTGCTGGAACGAAGATGGCCAGAGAGTAGAATCGTATTTCTGCAAGGACATAAAAAG TACATTCTCCAGGCAACCAACACTAGAACCAACAGCAATGACCCAACAGGAGAACCCCCGCCTCAAGA GCCTTTTTGGGAGCCTGGTAACTGGTCACATTGTTCTGCCACCTGTGGTCATTTGGGAGCCCGCATTC AGAGACCCCAGTGTGTGATGGCCAATGGGCAGGAAGTGAGTGAGGCCCTGTGTGATCACCTCCAGAAG CCACTGGCTGGGTTTGAGCCCTGTAACATCCGGGACTGCCCAGCGAGGTGGTTCACAAGTGTGTGGTC ACAGTGCTCTGTGTCTTGCGGTGAAGGATACCACAGTCGGCAGGTGACGTGCAAGCGGACAAAAGCCA ATGGAACTGTGCAGGTGGTGTCTCCAAGAGCATGTGCCCCTAAAGACCGGCCTCTGGGAAGAAAACCA TGTTTTGGTCATCCATGTGTTCAGTGGGAACCAGGGAACCGGTGTCCTGGACGTTGCATGGGCCGTGC TGTGAGGATGCAGCAGCGTCACACAGCTTGTCAACACAACAGCTCTGACTCCAACTGTGATGACAGAA AGAGACCCACCTTAAGAAGGAACTGCACATCAGGGGCCTGTGATGTGTGTTGGCACACAGGCCCTTGG AAGCCCTGTACAGCAGCCTGTGGCAGGGGTTTCCAGTCTCGGAAAGTCGACTGTATCCACACAAGGAG TTGCAAACCTGTGGCCAAGAGACACTGTGTACAGAAAAAGAAACCAATTTCCTGGCGGCACTGTCTTG GGCCCTCCTGTGATAGAGACTGCACAGACACAACTCACTACTGTATGTTTGTAAAACATCTTAATTTG TGTTCTCTAGACCGCTACAAACAAAGGTGCTGCCAGTCATGTCAAGAGGGATAAACCTTTGGAGGGGT CATGATGCTGCTGTGAAGATAAAAGTAGAATATAAAAGCTCTTTTCCCCATGTCGCTGATTCAAAAAC

ATGTATTTCTTAAAAGACTAGATTCTATGGATCAAACAGAGGTTGATGCAAAAACACCACTGTTAAGG

TGTAAAGTGAAATTTTCCAATGGTAGTTTTATATTCCAATTTTTTAAAATGATGTATTCAAGGATGAA

CAAAATACTATAGCATGCATGCCACTGCACTTGGGACCTCATCATGTCAGTTGAATCGAGAAATCACC iAAGATTATGAGTGCATCCTCACGTGCTGCCTCTTTCCTGTGATATGTAGACTAGCACAGAGTGGTACA

TCCTAAAAACTTGGGAAACACAGCAACCCATGACTTCCTCTTCTCTCAAGTTGCAGGTTTTCAACAGT jTTTATAAGGTATTTGCATTTTAGAAGCTCTGGCCAGTAGTTGTTAAGATGTTGGCATTAATGGCATTT

TCATAGATCCTTGGTTTAGTCTGTGAAAAAGAAACCATCTCTCTGGATAGGCTGTCACACTGACTGAC

CTAAGGGTTCATGGAAGCATGGCATCTTGTCCTTGCTTTTAGAACACCCATGGAAGAAAACACAGAGT

AGATATTGCTGTCATTTATACAACTACAGAAATTTATCTATGACCTAATGAGGCATCTCGGAAGTCAA

AGAAGAGGGAAAGTTAACCTTTTCTACTGATTTCGTAGTATATTCAGAGCTTTCTTTTAAGAGCTGTG

AATGAAACTTTTTCTAAGCACTATTCTATTGCACACAAACAGAAAACCAAAGCCTTATTAGACCTAAT

TTATGCATAAAGTAGTATTCCTGAGAACTTTATTTTGGAAAATTTATAAGAAAGTAATCCAAATAAGA

AACACGATAGTTGAAAATAATTTTTATAGTAAATAATTGTTTTGGGCTGATTTTTCAGTAAATCCAAA

GTGACTTAGGTTAGAAGTTACACTAAGGACCAGGGGTTGGAATCAGAATTTAGTTTAAGATTTGAGGA

AAAGGGTAAGGGTTAGTTTCAGTTTTAGGATTAGAGCTAGAATTGGGTTAGGTGAGAAAGAAAGTTAA

GGTTAAGGCTAGAGTTGTCTTTAAGGGTTAGGGTTAGGACCAGGTTAGGTCAGGGTTGGATTGGGTTT

AGATTGGGGCCAGTGCTGGTGTTAGTGATAGTGTCAGGATGGAGGTTAGGTTTGGAGTAAGCGTTGTT

GCTGAAGTGAGTTCAGGCTAGCATTAAATTGTAAGTTCTGAAGCTGATTTGGTTATGGGGTCTTTCCC

CTGTATACTACCAGTTGTGTCTTTAGATGGCACACAAGTCCAAATAAGTGGTCATACTTCTTTATTCA

GGGTCTCAGCTGCCTGTACACCTGCTGCCTACATCTTCTTGGCAACAAAGTTACCTGCCACAGGCTCT

GCTGAGCCTAGTTCCTGGTCAGTAATAACTGAACAGTGCATTTTGGCTTTGGATGTGTCTGTGGACAA

GCTTGCTGAGTTTCTCTACCATATTCTGAGCACACGGTCTCTTTTGTTCTAATTTCAGCTTCACTGAC

ACTGGGTTGAGCACTACTGTATGTGGAGGGTTTGGTGATTGGGAATGGATGGGGGACAGTGAGGAGGA

CACACCAGCCCATTAGTTGTTAATCATCAATCACATCTGATTGTTGAAGGTTATTAAATTAAAAGAAA

GATCATTTGTAACATACTCTTTGTATATATTTATTATATGAAAGGTGCAATATTTTATTTTGTACAGT

ATGTAATAAAGACATGGGACATATATTTTTCTTATTAACAAAATTTCATATTAAATTGCTTCACTTTG iTATTTAAAGTTAAAAGTTACTATTTTTCATTTGCTATTGTACTTTCATTGTTGTCATTCAATTGACAT

TCCTGTGTACTGTATTTTACTACTGTTTTTATAACATGAGAGTTAATGTTTCTGTTTCATGATCCTTA iTGTAATTCAGAAATAAATTTACTTTGATTATTCAGTGGCATCCTTAT

NOVlld, CG50513-03 SEQ ID NO: 90 1281 aa MW at 142825.9kD Protein Sequence

MPYDHFQPLPRWEHNP TACSVSCGGGIQRRSFVCVEESMHGEILQVEE KCMYAPKPKVMQTCNLFD CPKWI MEWSQCTVTCGRGLRYRWLCINHRGEHVGGCNPQLKLHIKEECVIPIPCY PKEKS VEAK LPWLKQAQELEETRIATEEPTFIPEP SACSTTCGPGVQVREVKCRVLLTFTQTETELPEEECEGPKL PTERPCLLEACDESPASRELDIPLPEDSETTYD EYAGFTPCTATCVGGHQEAIAVCLHIQTQQTVND SLCDMVHRPPA SQACNTEPCPPR HVGS GPCSATCGVGIQTRDVYCLHPGETPAPPEECRDEKPHA LQACNQFDCPPGWHIEE QQCSRTCGGGTQNRRVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTD CPPHLAVGDWSKCSVSCGVGIQRRKQVCQRLAA GRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSE MKT LGEQGPQILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQ SLIQ EKDGRCLQ NSIRLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETVVXjKLIGTDNRLIARPALREP REYPGMDHSE ANSLGVTWHKl^Q NNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNSWELKNKQFEAAVKQGAYS MDTAQFDELIRNMSQL ETGEVSDDLASQLIYQLVAELAKAQPTH QWRGIQEETPPAAQLRGETGSV SQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSRIGNTVYITKRTEVINILCDLITPSEATYT TKDGTLLQPSVKIILDGTGKIQIQNPTRKEQGIYECSVANHLGSDVESSSVLYAEAPVILSVERNIT KPEHNHLSVWGGIVEAALGANVTIRCPVKGVPQPNITWL RGGSLSGNVSLLFNGSLLLQNVSLENE GTYVCIATNALG AVATSVLHLLERR PESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPF EP GNWSHCSATCGHLGARIQRPQCVMANGQEVSEALCDHLQKPLAGFEPCNIRDCPAR FTSV SQCSVS CGEGYHSRQVTCKRTKANGTVQWSPRACAPKDRPLGRKPCFGHPCVQWEPGNRCPGRCMGRAVRMQQ RHTACQHNSSDSNCDDRKRPTLRRNCTSGACDVCWHTGP KPCTAACGRGFQSRKVDCIHTRSCKPVA KRHCVQKKKPIS RHCLGPSCDRDCTDTTHYCMFVKHLNLCSLDRYKQRCCQSCQEG

NOVl le, CG50513-04 SEQ ID NO: 91 7260 bp DNA Sequence ORF Start: ATG at 136 ORF Stop: TAA at 5209

CGCACGAGGTGTTGACGGGCGGCTTCTGCCAACTTCTCCCCAGCGCGCGCCGAGCCCGCGCGGCCCCG

GGGCTGCACGTCCCAGATACTTCTGCGGCGCAAGGCTACAACTGAGACCCGGAGGAGACTAGACCCCA

TGGCTTCCTGGACGAGCCCCTGGTGGGTGCTGATAGGGATGGTCTTCATGCACTCTCCCCTCCCGCAG ACCACAGCTGAGAAATCTCCTGGAGCCTATTTCCTTCCCGAGTTTGCACTTTCTCCTCAGGGAAGTTT TCTGGAAGACACAACAGGGGAGCAGTTCCTCACTTATCGCTATGATGACCAGACCTCAAGAAACACTC GTTCAGATGAAGACAAAGATGGCAACTGGGATGCTTGGGGCGACTGGAGTGACTGCTCCCGGACCTGT GGGGGAGGAGCATCATATTCTCTGCGGAGATGTTTGACTGGAAGGAATTGTGAAGGGCAGAACATTCG GTACAAGACATGCAGCAATCATGACTGCCCTCCAGATGCAGAAGATTTCAGAGCCCAGCAGTGCTCAG CCTACAATGATGTCCAGTATCAGGGGCATTACTATGAATGGCTTCCACGATATAATGATCCTGCTGCC CCGTGTGCACTCAAGTGTCATGCACAAGGACAAAACTTGGTGGTGGAGCTGGCACCTAAGGTACTGGA TGGAACTCGTTGCAACACGGACTCCTTGGACATGTGTATCAGTGGCATCTGTCAGGCAGTGGGCTGCG ATCGGCAACTGGGAAGCAATGCCAAGGAGGACAACTGTGGAGTCTGTGCCGGCGATGGCTCCACCTGC AGGCTTGTACGGGGACAATCAAAGTCACACGTTTCTCCTGAAAAAAGAGAAGAAAATGTAATTGCTGT TCCTTTGGGAAGTCGAAGTGTGAGAATTACAGTGAAAGGACCTGCCCACCTCTTTATTGAATCAAAAA CACTTCAAGGAAGCAAAGGAGAACACAGCTTTAACAGCCCCGGCGTCTTTGTCGTAGAAAACACAACA GTGGAATTTCAGAGGGGCTCCGAGAGGCAAACTTTTAAGATTCCAGGACCTCTGATGGCTGATTTCAT CTTCAAGACCAGGTACACTGCAGCCAAAGACAGCGTGGTTCAGTTCTTCTTTTACCAGCCCATCAGTC ATCAGTGGAGACAAACTGACTTCTTTCCCTGCACTGTGACGTGTGGAGGAGGTTATCAGCTCAATTCT GCTGAATGTGTGGATATCCGCTTGAAGAGGGTAGTTCCTGACCATTATTGTCACTACTACCCTGAAAA TGTAAAACCAAAACCAAAACTGAAGGAATGCAGCATGGATCCCTGCCCATCAAGTGATGGATTTAAAG AGATAATGCCCTATGACCACTTCCAACCTCTTCCTCGCTGGGAACATAATCCTTGGACTGCATGTTCC GTGTCCTGTGGAGGAGGGATTCAGAGACGGAGCTTTGTGTGTGTAGAGGAATCCATGCATGGAGAGAT ATTGCAGGTGGAAGAATGGAAGTGCATGTACGCACCCAAACCCAAGGTTATGCAAACTTGTAATCTGT TTGATTGCCCCAAGTGGATTGCCATGGAGTGGTCTCAGTGCACAGTGACTTGTGGCCGAGGGTTACGG TACCGGGTTGTTCTGTGTATTAACCACCGCGGAGAGCATGTTGGGGGCTGCAATCCACAACTGAAGTT ACACATCAAAGAAGAATGTGTCATTCCCATCCCGTGTTATAAACCAAAAGAAAAAAGTCCAGTGGAAG CAAAATTGCCTTGGCTGAAACAAGCACAAGAACTAGAAGAGACCAGAATAGCAACAGAAGAACCAACG TTCATTCCAGAACCCTGGTCAGCCTGCAGTACCACGTGTGGGCCGGGTGTGCAGGTCCGTGAGGTGAA GTGCCGTGTGCTCCTCACATTCACGCAGACTGAGACTGAGCTGCCCGAGGAAGAGTGTGAAGGCCCCA AGCTGCCCACCGAACGGCCCTGCCTCCTGGAAGCATGTGATGAGAGCCCGGCCTCCCGAGAGCTAGAC ATCCCTCTCCCTGAGGACAGTGAGACGACTTACGACTGGGAGTACGCTGGGTTCACCCCTTGCACAGC AACATGCGTGGGAGGCCATCAAGAAGCCATAGCAGTGTGCTTACATATCCAGACCCAGCAGACAGTCA ATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCCATGAGCCAGGCCTGTAACACAGAGCCCTGT CCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTCAGCTACCTGTGGAGTTGGAATTCAGACCCG AGATGTGTACTGCCTGCACCCAGGGGAGACCCCTGCCCCTCCTGAGGAGTGCCGAGATGAAAAGCCCC ATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCTGGCTGGCACATTGAAGAATGGCAGCAGTGT TCCAGGACTTGTGGCGGGGGAACTCAGAACAGAAGAGTCACCTGTCGGCAGCTGCTAACGGATGGCAG CTTTTTGAATCTCTCAGATGAATTGTGCCAAGGACCCAAGGCATCGTCTCACAAGTCCTGTGCCAGGA CAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCGAAGTGTTCTGTCAGTTGTGGTGTTGGAATC CAGAGAAGAAAGCAGGTGTGTCAAAGGCTGGCAGCCAAAGGTCGGCGCATCCCCCTCAGTGAGATGAT GTGCAGGGATCTACCAGGGTTCCCTCTTGTAAGATCTTGCCAGATGCCTGAGTGCAGTAAAATCAAAT CAGAGATGAAGACAAAACTTGGTGAGCAGGGTCCGCAGATCCTCAGTGTCCAGAGAGTCTACATTCAG ACAAGGGAAGAGAAGCGTATTAACCTGACCATTGGTAGCAGAGCCTATTTGCTGCCCAACACATCCGT GATTATTAAGTGCCCCGTGCGACGATTCCAGAAATCTCTGATCCAGTGGGAGAAGGATGGCCGTTGCC TGCAGAACTCCAAACGGCTTGGCATCACCAAGTCAGGCTCACTAAAAATCCACGGTCTTGCTGCCCCC GACATCGGCGTGTACCGGTGCATTGCAGGCTCTGCACAGGAAACAGTTGTGCTCAAGCTCATTGGTAC TGACAACCGGCTCATCGCACGCCCAGCCCTCAGGGAGCCTATGAGGGAATATCCTGGGATGGACCACA GCGAAGCCAATAGTTTGGGAGTCACATGGCACAAAATGAGGCAAATGTGGAATAACAAAAATGACCTT TATCTGGATGATGACCACATTAGTAACCAGCCTTTCTTGAGAGCTCTGTTAGGCCACTGCAGCAATTC TGCAGGAAGCACCAACTCCTGGGAGTTGAAGAATAAGCAGTTTGAAGCAGCAGTTAAACAAGGAGCAT ATAGCATGGATACAGCCCAGTTTGATGAGCTGATAAGAAACATGAGTCAGCTCATGGAAACCGGAGAG 'GTCAGCGATGATCTTGCGTCCCAGCTGATATATCAGCTGGTGGCCGAATTAGCCAAGGCACAGCCAAC ACACATGCAGTGGCGGGGCATCCAGGAAGAGACACCTCCTGCTGCTCAGCTCAGAGGGGAAACAGGGA IGTGTGTCCCAAAGCTCGCATGCAAAAAACTCAGGCAAGCTGACATTCAAGCCGAAAGGACCTGTTCTC 'ATGAGGCAAAGCCAACCTCCCTCAATTTCATTTAATAAAACAATAAATTCCAGGATTGGAAATACAGT JATACATTACAAAAAGGACAGAGGTCATCAATATACTGTGTGACCTTATTACCCCCAGTGAGGCCACAT ATACATGGACCAAGGATGGAACCTTGTTACAGCCCTCAGTAAAAATAATTTTGGATGGAACTGGGAAG ATACAGATACAGAATCCTACAAGGAAAGAACAAGGCATATATGAATGTTCTGTAGCTAATCATCTTGG TTCAGATGTGGAAAGTTCTTCTGTGCTGTATGCAGAGGCACCTGTCATCTTGTCTGTTGAAAGAAATA JTCACCAAACCAGAGCACAACCATCTGTCTGTTGTGGTTGGAGGCATCGTGGAGGCAGCCCTTGGAGCA AACGTGACAATCCGATGTCCTGTAAAAGGTGTCCCTCAGCCTAATATAACTTGGTTGAAGAGAGGAGG ATCTCTGAGTGGCAATGTTTCCTTGCTTTTCAATGGATCCCTGTTGTTGCAGAATGTTTCCCTTGAAA ATGAAGGAACCTACGTCTGCATAGCCACCAATGCTCTTGGAAAGGCAGTGGCAACATCTGTATTCCAC TTGCTGGAACGAAGATGGCCAGAGAGTAGAATCGTATTTCTGCAAGGACATAAAAAGTACATTCTCCA

GGCAACCAACACTAGAACCAACAGCAATGACCCAACAGGAGAACCCCCGCCTCAAGAGCCTTTTΓGGG

AGCCTGGTAACTGGTCACATTGTTCTGCCACCTGTGGTCATTTGGGAGCCCGCATTCAGAGACCCCAG TGTGTGATGGCCAATGGGCAGGAAGTGAGTGAGGCCCTGTGTGATCACCTCCAGAAGCCACTGGCTGG GTTTGAGCCCTGTAACATCCGGGACTGCCCAGCGAGGTGGTTCACAAGTGTGTGGTCACAGTGCTCTG TGTCTTGCGGTGAAGGATACCACAGTCGGCAGGTGACGTGCAAGCGGACAAAAGCCAATGGAACTGTG CAGGTGGTGTCTCCAAGAGCATGTGCCCCTAAAGACCGGCCTCTGGGAAGAAAACCATGTTTTGGTCA TCCATGTGTTCAGTGGGAACCAGGGAACCGGTGTCCTGGACGTTGCATGGGCCGTGCTGTGAGGATGC AGCAGCGTCACACAGCTTGTCAACACAACAGCTCTGACTCCAACTGTGATGACAGAAAGAGACCCACC TTAAGAAGGAACTGCACATCAGGGGCCTGTGATGTGTGTTGGCACACAGGCCCTTGGAAGCCCTGTAC AGCAGCCTGTGGCAGGGGTTTCCAGTCTCGGAAAGTCGACTGTATCCACACAAGGAGTTGCAAACCTG TGGCCAAGAGACACTGTGTACAGAAAAAGAAACCAATTTCCTGGCGGCACTGTCTTGGGCCCTCCTGT GATAGAGACTGCACAGACACAACTCACTACTGTATGTTTGTAAAACATCTTAATTTGTGTTCTCTAGA CCGCTACAAACAAAGGTGCTGCCAGTCATGTCAAGAGGGATAAACCTTTGGAGGGGTCATGATGCTGC TGTGAAGATAAAAGTAGAATATAAAAGCTCTTTTCCCCATGTCGCTGATTCAAAAACATGTATTTCTT

AAAAGACTAGATTCTATGGATCAAACAGAGGTTGATGCAAAAACACCACTGTTAAGGTGTAAAGTGAA

ATTTTCCAATGGTAGTTTTATATTCCAATTTTTTAAAATGATGTATTCAAGGATGAACAAAATACTAT

AGCATGCATGCCACTGCACTTGGGACCTCATCATGTCAGTTGAATCGAGAAATCACCAAGATTATGAG

TGCATCCTCACGTGCTGCCTCTTTCCTGTGATATGTAGACTAGCACAGAGTGGTACATCCTAAAAACT

TGGGAAACACAGCAACCCATGACTTCCTCTTCTCTCAAGTTGCAGGTTTTCAACAGTTTTATAAGGTA iTTTGCATTTTAGAAGCTCTGGCCAGTAGTTGTTAAGATGTTGGCATTAATGGCATTTTCATAGATCCT iTGGTTTAGTCTGTGAAAAAGAAACCATCTCTCTGGATAGGCTGTCACACTGACTGACCTAAGGGTTCA

TGGAAGCATGGCATCTTGTCCTTGCTTTTAGAACACCCATGGAAGAAAACACAGAGTAGATATTGCTG

ITCATTTATACAACTACAGAAATTTATCTATGACCTAATGAGGCATCTCGGAAGTCAAAGAAGAGGGAA

AGTTAACCTTTTCTACTGATTTCGTAGTATATTCAGAGCTTTCTTTTAAGAGCTGTGAATGAAACTTT

TTCTAAGCACTATTCTATTGCACACAAACAGAAAACCAAAGCCTTATTAGACCTAATTTATGCATAAA GTAGTATTCCTGAGAACTTTATTTTGGAAAATTTATAAGAAAGTAATCCAAATAAGAAACACGATAGT TGAAAATAATTTTTATAGTAAATAATTGTTTTGGGCTGATTTTTCAGTAAATCCAAAGTGACTTAGGT

TAGAAGTTACACTAAGGACCAGGGGTTGGAATCAGAATTTAGTTTAAGATTTGAGGAAAAGGGTAAGG GTTAGTTTCAGTTTTAGGATTAGAGCTAGAATTGGGTTAGGTGAGAAAGAAAGTTAAGGTTAAGGCTA GAGTTGTCTTTAAGGGTTAGGGTTAGGACCAGGTTAGGTCAGGGTTGGATTGGGTTTAGATTGGGGCC

AGTGCTGGTGTTAGTGATAGTGTCAGGATGGAGGTTAGGTTTGGAGTAAGCGTTGTTGCTGAAGTGAG

TTCAGGCTAGCATTAAATTGTAAGTTCTGAAGCTGATTTGGTTATGGGGTCTTTCCCCTGTATACTAC CAGTTGTGTCTTTAGATGGCACACAAGTCCAAATAAGTGGTCATACTTCTTTATTCAGGGTCTCAGCT

GCCTGTACACCTGCTGCCTACATCTTCTTGGCAACAAAGTTACCTGCCACAGGCTCTGCTGAGCCTAG TTCCTGGTCAGTAATAACTGAACAGTGCATTTTGGCTTTGGATGTGTCTGTGGACAAGCTTGCTGAGT TTCTCTACCATATTCTGAGCACACGGTCTCTTTTGTTCTAACTTCAGCTTCACTGACACTGGGTTGAG

CACTACTGTATGTGGAGGGTTTGGTGATTGGGAATGGATGGGGGACAGTGAGGAGGACACACCAGCCC jATTAGTTGTTAATCATCAATCACATCTGATTGTTGAAGGTTATTAAATTAAAAGAAAGATCATTTGTA

ACATACTCTTTGTATATATTTATTATATGAAAGGTGCAATATTTTATTTTGTACAGTATGTAATAAAG

ACATGGGACATATATTTTTCTTATTAACAAAATTTCATATTAAATTGCTTCACTTTGTATTTAAAGTT

AAAAGTTACTATTTTTCATTTGCTATTGTACTTTCATTGTTGTCATTCAATTGACATTCCTGTGTACT GTATTTTACTACTGTTTTTATAACATGAGAGTTAATGTTTCTGTTTCATGATCCTTATGTAATTCAGA

AATAAATTTACTTTGATTATTCAGTGGCATCCTTATAAAAAAAAAAAAAAAA

NOVl le, CG50513-04 SEQ ID NO: 92 1691 aa MW at 188743.8kD Protein Sequence

MASWTSPWWVLIGMVFMHSPLPQTTAEKSPGAYFLPEFALSPQGSFLEDTTGEQFLTYRYDDQTSRNT RSDED DGNWDAWGD SDCSRTCGGGASYSLRRCLTGRNCEGQNIRYKTCSNHDCPPDAΞDFRAQQCS AYNDVQYQGHYYE LPRYNDPAAPCAL CHAQGQNLWELAPKVLDGTRCNTDSLDMCISGICQAVGC DRQLGSNAKEDNCGVCAGDGSTCRLVRGQSKSHVSPEKREENVIAVPLGSRSVRITVKGPAHLFIESK TLQGSKGEHSFNSPGVFWENTTVEFQRGSERQTFKIPGPLMADFIFKTRYTAAKDSWQFFFYQPIS HQWRQTDFFPCTVTCGGGYQLNSAECVDIRLKRWPDHYCHYYPENVKP PKLKECSMDPCPSSDGFK EIMPYDHFQPLPR EHNP TACSVSCGGGIQRRSFVCVEESMHGEILQVEEW CMYAPKPKV QTCNI. FDCPK IAME SQCTVTCGRGLRYRWLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKP EKSPVE AKLP LKQAQELEETRIATEEPTFIPEP SACSTTCGPGVQVREVKCRVLLTFTQTETELPEEECEGP KLPTERPCLLEACDESPASRELDIPLPEDSETTYD EYAGFTPCTATCVGGHQEAIAVCLHIQTQQTV NDSLCDMVHRPPAMSQACNTEPCPPRWHVGS GPCSATCGVGIQTRDVYCLHPGETPAPPEECRDEKP HALQACNQFDCPPG HIEEWQQCSRTCGGGTQNRRVTCRQLLTDGSFLNLSDELCQGPKASSHKSCAR TDCPPHLAVGD SKCSVSCGVGIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKIK SEMKTKLGEQGPQILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQ EKDGRC LQNSKRLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETVVLKLIGTDNRLIARPALREPMREYPGMDH SEANSLGVT HKMRQMrøsTNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNS ELKNKQFEAAVKQGA YSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELA AQPTHMQ RGIQEETPPAAQLRGETG SVSQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSRIGNTVYITKRTEVINILCDLITPSEAT YT TKDGTLLQPSV IILDGTGKIQIQNPTR EQGIYECSVANHLGSDVESSSVLYAEAPVILSVERN ITKPEHNHLSVWGGIVEAALGANVTIRCPVKGVPQPNITWLKRGGSLSGNVSLLFNGSLLLQNVSLE NEGTYVCIATNALGKAVATSVFHLLERR PESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPFW EPGNWSHCSATCGHLGARIQRPQCrVMANGQEVSEALCDHLQKPLAGFEPCNIRDCPAR FTSVWSQCS VSCGEGYHSRQVTCKRT ANGTVQWSPRACAP DRPLGRKPCFGHPCVQ EPGNRCPGRCMGRAVRM QQRHTACQHNSSDSNCDDR RPTLRRNCTSGACDVC HTGPWKPCTAACGRGFQSRKVDCIHTRSCKP VAKRHCVQKKKPISWRHCLGPSCDRDCTDTTHYCMFVKHLNLCSLDRYKQRCCQSCQEG

|NOVl lf, CG50513-05 [SEQ ID NO: 93 J6294 bp

DNA Sequence ORF Start: ATG at 416 ORF Stop: TAA at 4259

TAATAGAGACCTTTCAAAGGACAAATTCTGTGAAATAAAGTGGTTTTCTGAAGAGCCTACTAATAGGA

CAGTGTGTTAATATCACTAATAAGAGAGTAATGATTATAAAAAGGAATAAATTTATTGAAATTGCAAG

ATACTTTTCTCCTTTGATTAATATACTGCTAGTTTAGTTTTCTACATTTTCAAATAGAACTGGGGAAT

TTGTGTCGTAGATATTCTTGACAACTAAAGAGATGGTGGCTGAATTTTTGGGAATGGTTGATAACACT

TGATATTTTTAGTTTCCAATTTGGAAGAGCTCTGTCTCTTGGGATGTCAAATATTATATTCGTCAATT

AATGAATGTGTTAATTTATTATAGAAATGATATTCTCACAATGATTTCATTTGTAGTGATGGATTTAA

AGAGATAATGCCCTATGACCACTTCCAACCTCTTCCTCGCTGGGAACATAATCCTTGGACTGCATGTT

CCGTGTCCTGTGGAGGAGGGATTCAGAGACGGAGCTTTGTGTGTGTAGAGGAATCCATGCATGGAGAG ATATTGCAGGTGGAAGAATGGAAGTGCATGTACGCACCCAAACCCAAGGTTATGCAAACTTGTAATCT GTTTGATTGCCCCAAGTGGATTGCCATGGAGTGGTCTCAGTGCACAGTGACTTGTGGCCGAGGGTTAC GGTACCGGGTTGTTCTGTGTATTAACCACCGCGGAGAGCATGTTGGGGGCTGCAATCCACAACTGAAG TTACACATCAAAGAAGAATGTGTCATTCCCATCCCGTGTTATAAACCAAAAGAAAAAAGTCCAGTGGA AGCAAAATTGCCTTGGCTGAAACAAGCACAAGAACTAGAAGAGACCAGAATAGCAACAGAAGAACCAA CGTTCATTCCAGAACCCTGGTCAGCCTGCAGTACCACGTGTGGGCCGGGTGTGCAGGTCCGTGAGGTG AAGTGCCGTGTGCTCCTCACATTCACGCAGACTGAGACTGAGCTGCCCGAGGAAGAGTGTGAAGGCCC CAAGCTGCCCACCGAACGGCCCTGCCTCCTGGAAGCATGTGATGAGAGCCCGGCCTCCCGAGAGCTAG ACATCCCTCTCCCTGAGGACAGTGAGACGACTTACGACTGGGAGTACGCTGGGTTCACCCCTTGCACA GCAACATGCGTGGGAGGCCATCAAGAAGCCATAGCAGTGTGCTTACATATCCAGACCCAGCAGACAGT CAATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCCATGAGCCAGGCCTGTAACACAGAGCCCT GTCCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTCAGCTACCTGTGGAGTTGGAATTCAGACC CGAGATGTGTACTGCCTGCACCCAGGGGAGACCCCTGCCCCTCCTGAGGAGTGCCGAGATGAAAAGCC CCATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCTGGCTGGCACATTGAAGAATGGCAGCAGT GTTCCAGGACTTGTGGCGGGGGAACTCAGAACAGAAGAGTCACCTGTCGGCAGCTGCTAACGGATGGC AGCTTTTTGAATCTCTCAGATGAATTGTGCCAAGGACCCAAGGCATCGTCTCACAAGTCCTGTGCCAG GACAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCGAAGTGTTCTGTCAGTTGTGGTGTTGGAA TCCAGAGAAGAAAGCAGGTGTGTCAAAGGCTGGCAGCCAAAGGTCGGCGCATCCCCCTCAGTGAGATG LATGTGCAGGGATCTACCAGGGCTCCCTCTTGTAAGATCTTGCCAGATGCCTGAGTGCAGTAAAATCAA ATCAGAGATGAAGACAAAACTTGGTGAGCAGGGTCCGCAGATCCTCAGTGTCCAGAGAGTCTACATTC 'AGACAAGGGAAGAGAAGCGTATTAACCTGACCATTGGTAGCAGAGCCTATTTGCTGCCCAACACATCC GTGATTATTAAGTGCCCAGTGCGACGATTCCAGAAATCTCTGATCCAGTGGGAGAAGGATGGCCGTTG CCTGCAGAACTCCAAACGGCTTGGCATCACCAAGTCAGGCTCACTAAAAATCCACGGTCTTGCTGCCC CCGACATCGGCGTGTACCGGTGCATTGCAGGCTCTGCACAGGAAACAGTTGTGCTCAAGCTCATTGGT ACTGACAACCGGCTCATCGCACGCCCAGCCCTCAGGGAGCCTATGAGGGAATATCCTGGGATGGACCA CAGCGAAGCCAATAGTTTGGGAGTCACATGGCACAAAATGAGGCAAATGTGGAATAACAAAAATGACC TTTATCTGGATGATGACCACATTAGTAACCAGCCTTTCTTGAGAGCTCTGTTAGGCCACTGCAGCAAT TCTGCAGGAAGCACCAACTCCTGGGAGTTGAAGAATAAGCAGTTTGAAGCAGCAGTTAAACAAGGAGC ATATAGCATGGATACAGCCCAGTTTGATGAGCTGATAAGAAACATGAGTCAGCTCATGGAAACCGGAG AGGTCAGCGATGATCTTGCGTCCCAGCTGATATATCAGCTGGTGGCCGAATTAGCCAAGGCACAGCCA ACACACATGCAGTGGCGGGGCATCCAGGAAGAGACACCTCCTGCTGCTCAGCTCAGAGGGGAAACAGG GAGTGTGTCCCAAAGCTCGCATGCAAAAAACTCAGGCAAGCTGACATTCAAGCCGAAAGGACCTGTTC TCATGAGGCAAAGCCAACCTCCCTCAATTTCATTTAATAAAACAATAAATTCCAGGATTGGAAATACA GTATACATTACAAAAAGGACAGAGGTCATCAATATACTGTGTGACCTTATTACCCCCAGTGAGGCCAC ATATACATGGACCAAGGATGGAACCTTGTTACAGCCCTCAGTAAAAATAATTTTGGATGGAACTGGGA AGATACAGATACAGAATCCTACAAGGAAAGAACAAGGCATATATGAATGTTCTGTAGCTAATCATCTT GGTTCAGATGTGGAAAGTTCTTCTGTGCTGTATGCAGAGGCACCTGTCATCTTGTCTGTTGAAAGAAA TATCACCAAACCAGAGCACAACCATCTGTCTGTTGTGGTTGGAGGCATCGTGGAGGCAGCCCTTGGAG CAAACGTGACAATCCGATGTCCTGTAAAAGGTGTCCCTCAGCCTAATATAACTTGGTTGAAGAGAGGA GGATCTCTGAGTGGCAATGTTTCCTTGCTTTTCAATGGATCCCTGTTGTTGCAGAATGTTTCCCTTGA AAATGAAGGAACCTACGTCTGCATAGCCACCAATGCTCTTGGAAAGGCAGTGGCAACATCTGTACTCC ACTTGCTGGAACGAAGATGGCCAGAGAGTAGAATCGTATTTCTGCAAGGACATAAAAAGTACATTCTC CAGGCAACCAACACTAGAACCAACAGCAATGACCCAACAGGAGAACCCCCGCCTCAAGAGCCTTTTTG GGAGCCTGGTAACTGGTCACATTGTTCTGCCACCTGTGGTCATTTGGGAGCCCGCATTCAGAGACCCC AGTGTGTGATGGCCAATGGGCAGGAAGTGAGTGAGGCCCTGTGTGATCACCTCCAGAAGCCACTGGCT GGGTTTGAGCCCTGTAACATCCGGGACTGCCCAGCGAGGTGGTTCACAAGTGTGTGGTCACAGTGCTC TGTGTCTTGCGGTGAAGGATACCACAGTCGGCAGGTGACGTGCAAGCGGACAAAAGCCAATGGAACTG TGCAGGTGGTGTCTCCAAGAGCATGTGCCCCTAAAGACCGGCCTCTGGGAAGAAAACCATGTTTTGGT CATCCATGTGTTCAGTGGGAACCAGGGAACCGGTGTCCTGGACGTTGCATGGGCCGTGCTGTGAGGAT GCAGCAGCGTCACACAGCTTGTCAACACAACAGCTCTGACTCCAACTGTGATGACAGAAAGAGACCCA CCTTAAGAAGGAACTGCACATCAGGGGCCTGTGATGTGTGTTGGCACACAGGCCCTTGGAAGCCCTGT ACAGCAGCCTGTGGCAGGGGTTTCCAGTCTCGGAAAGTCGACTGTATCCACACAAGGAGTTGCAAACC TGTGGCCAAGAGACACTGTGTACAGAAAAAGAAACCAATTTCCTGGCGGCACTGTCTTGGGCCCTCCT GTGATAGAGACTGCACAGACACAACTCACTACTGTATGTTTGTAAAACATCTTAATTTGTGTTCTCTA GACCGCTACAAACAAAGGTGCTGCCAGTCATGTCAAGAGGGATAAACCTTTGGAGGGGTCATGATGCT GCTGTGAAGATAAAAGTAGAATATAAAAGCTCTTTTCCCCATGTCGCTGATTCAAAAACATGTATTTC

TTAAAAGACTAGATTCTATGGATCAAACAGAGGTTGATGCAAAAACACCACTGTTAAGGTGTAAAGTG

AAATTTTCCAATGGTAGTTTTATATTCCAATTTTTTAAAATGATGTATTCAAGGATGAACAAAATACT

ATAGCATGCATGCCACTGCACTTGGGACCTCATCATGTCAGTTGAATCGAGAAATCACCAAGATTATG

AGTGCATCCTCACGTGCTGCCTCTTTCCTGTGATATGTAGACTAGCACAGAGTGGTACATCCTAAAAA

CTTGGGAAACACAGCAACCCATGACTTCCTCTTCTCTCAAGTTGCAGGTTTTCAACAGTTTTATAAGG

TATTTGCATTTTAGAAGCTCTGGCCAGTAGTTGTTAAGATGTTGGCATTAATGGCATTTTCATAGATC

CTTGGTTTAGTCTGTGAAAAAGAAACCATCTCTCTGGATAGGCTGTCACACTGACTGACCTAAGGGTT

CATGGAAGCATGGCATCTTGTCCTTGCTTTTAGAACACCCATGGAAGAAAACACAGAGTAGATATTGC

TGTCATTTATACAACTACAGAAATTTATCTATGACCTAATGAGGCATCTCGGAAGTCAAAGAAGAGGG

AAAGTTAACCTTTTCTACTGATTTCGTAGTATATTCAGAGCTTTCTTTTAAGAGCTGTGAATGAAACT

TTTTCTAAGCACTATTCTATTGCACACAAACAGAAAACCAAAGCCTTATTAGACCTAATTTATGCATA

AAGTAGTATTCCTGAGAACTTTATTTTGGAAAATTTATAAGAAAGTAATCCAAATAAGAAACACGATA GTTGAAAATAATTTTTATAGTAAATAATTGTTTTGGGCTGATTTTTCAGTAAATCCAAAGTGACTTAG GTTAGAAGTTACACTAAGGACCAGGGGTTGGAATCAGAATTTAGTTTAAGATTTGAGGAAAAGGGTAA

GGGTTAGTTTCAGTTTTAGGATTAGAGCTAGAATTGGGTTAGGTGAGAAAGAAAGTTAAGGTTAAGGC TAGAGTTGTCTTTAAGGGTTAGGGTTAGGACCAGGTTAGGTCAGGGTTGGATTGGGTTTAGATTGGGG CCAGTGCTGGTGTTAGTGATAGTGTCAGGATGGAGGTTAGGTTTGGAGTAAGCGTTGTTGCTGAAGTG AGTTCAGGCTAGCATTAAATTGTAAGTTCTGAAGCTGATTTGGTTATGGGGTCTTTCCCCTGTATACT ACCAGTTGTGTCTTTAGATGGCACACAAGTCCAAATAAGTGGTCATACTTCTTTATTCAGGGTCTCAG CTGCCTGTACACCTGCTGCCTACATCTTCTTGGCAACAAAGTTACCTGCCACAGGCTCTGCTGAGCCT

AGTTCCTGGTCAGTAATAACTGAACAGTGCATTTTGGCTTTGGATGTGTCTGTGGACAAGCTTGCTGA

GTTTCTCTACCATATTCTGAGCACACGGTCTCTTTTGTTCTAATTTCAGCTTCACTGACACTGGGTTG

AGCACTACTGTATGTGGAGGGTTTGGTGATTGGGAATGGATGGGGGACAGTGAGGAGGACACACCAGC

CCATTAGTTGTTAATCATCAATCACATCTGATTGTTGAAGGTTATTAAATTAAAAGAAAGATCATTTG

TAACATACTCTTTGTATATATTTATTATATGAAAGGTGCAATATTTTATTTTGTACAGTATGTAATAA

AGACATGGGACATATATTTTTCTTATTAACAAAATTTCATATTAAATTGCTTCACTTTGTATTTAAAG

TTAAAAGTTACTATTTTTCATTTGCTATTGTACTTTCATTGTTGTCATTCAATTGACATTCCTGTGTA

CTGTATTTTACTACTGTTTTTATAACATGAGAGTTAATGTTTCTGTTTCATGATCCTTATGTAATTCA

GAAATAAATTTACTTTGATTATTCAGTGGCATCCTTAT

NOVl lf, CG50513-05 SEQ ID NO: 94 1281 aa MW at 142791.9kD Protein Sequence

MPYDHFQPLPRWEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEE CMYAPKPKV QTCNLFD CPKWIAMEWSQCTVTCGRGLRYRWLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEKSPVEAK LP LKQAQELΞETRIATEEPTFIPEP SACSTTCGPGVQVREVKCRVLLTFTQTETELPEEECEGPKL PTERPCLLEACDESPASRELDIPLPEDSETTYD EYAGFTPCTATCVGGHQEAIAVCLHIQTQQTVND SLCDiVIVHRPPAMSQACNTEPCPPR HVGS GPCSATCGVGIQTRDVYCLHPGΞTPAPPEECRDEKPHA LQACNQFDCPPGWHIEE QQCSRTCGGGTQNRRVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTD CPPHLAVGD SKCSVSCGVGIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGLPLVRSCQ PECSKIKSE KTKLGEQGPQILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQ EKDGRCLQ NSKRLGIT SGSLKIHGIiAAPDIGVYRCIAGSAQETVVLKLIGTDNRLIARPALREPMREYPGMDHSE ANSLGVT HKMRQMWNNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNSWELKN QFEAAV QGAYS MDTAQFDΞLIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQ RGIQEETPPAAQLRGETGSV SQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSRIGNTVYITKRTEVINILCDLITPSEATYT WTKDGTLLQPSVKIILDGTGKIQIQNPTRKEQGIYECSVANHLGSDVESSSVLYAEAPVILSVERNIT KPEHNHLSVWGGIVEAALGANVTIRCPV GVPQPNIT LKRGGSLSGNVSLLFNGSLLLQNVSLENE GTYVCIATNALGKAVATSVLHLLERRWPESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPFWEP GNWSHCSATCGHLGARIQRPQCVMANGQEVSEALCDHLQKPLAGFEPCNIRDCPAR FTSV SQCSVS CGEGYHSRQVTCKRTKANGTVQWSPRACAPKDRPLGRKPCFGHPCVQWEPGNRCPGRCMGRAVRMQQ RHTACQHNSSDSNCDDRKRPTLRRNCTSGACDVCWHTGP KPCTAACGRGFQSRKVDCIHTRSCKPVA KRHCVQKK PIS RHCLGPSCDRDCTDTTHYCMFV HLNLCS DRYKQRCCQSCQEG

NOV 11 g, CG50513-06 SEQ ID NO: 95 2912 bp DNA Sequence ORF Start: ATG at 98 ORF Stop: TAA at 2876

CAGCTTTAACAGCCCCGGCGTCTTTGTCGTAGAAAACACAACAGTGGAATTTTAGAGGGGCTCCGAGA

GGCAAACTTTTAAGATTCCAGGCCCTTTGATGGCTGATTTCATCTTCAAGACCAGGTACACTGCAGCC

AAAGACAGCGTGGTTCAGTTCTTCTTTTACCAGCCCATCAGTCATCAGTGGAGACAAACTGACTTCTT TCCCTGCACTGTGACGTGTGGAGGAGGTTATCAGCTCAATTCTGCTGAATGTGTGGATATCCGCTTGA AGAGGGTAGTTCCTGACCATTATTGTCACTACTACCCTGAAAATGTAAAACCAAAACCAAAACTGAAG GAATGCAGCATGGATCCCTGCCCATCAAGTGATGGATTTAAAGAGATAATGCCCTATGACCACTTCCA ACCTCTTCCTCGCTGGGAACATAATCCTTGGACTGCATGTTCCGTGTCCTGTGGAGGAGGGATTCAGA GACGGAGCTTTGTGTGTGTAGAGGAATCCATGCATGGAGAGATATTGCAGGTGGAAGAATGGAAGTGC ATGTACGCACCCAAACCCAAGGTTATGCAAACTTGTAATCTGTTTGATTGCCCCAAGTGGATTGCCAT GGAGTGGTCTCAGTGCACAGTGACTTGTGGCCGAGGGTTACGGTACCGGGTTGTTCTGTGTATTAACC ACCGCGGAGAGCATGTTGGGGGCTGCAATCCACAACTGAAGTTACACATCAAAGAAGAATGTGTCATT CCCATCCCGTGTTATAAACCAAAAGAAAAAAGTCCAGTGGAAGCAAAATTGCCTTGGCTGAAACAAGC ACAAGAACTAGAAGAGACCAGAATAGCAACAGAAGAACCAACGTTCATTCCAGAACCCTGGTCAGCCT GCAGTACCACGTGTGGGCCGGGTGTGCAGGTCCGTGAGGTGAAGTGCCGTGTGCTCCTCACATTCACG CAGACTGAGACTGAGCTGCCCGAGGAAGAGTGTGAAGGCCCCAAGCTGCCCACCGAACGGCCCTGCCT CCTGGAAGCATGTGATGAGAGCCCGGCCTCCCGAGAGCTAGACATCCCTCTCCCTGAGGACAGTGAGA CGACTTACGACTGGGAGTACGCTGGGTTCACCCCTTGCACAGCAACATGCGTGGGAGGCCATCAAGAA GCCATAGCAGTGTGCTTACATATCCAGACCCAGCAGACAGTCAATGACAGCTTGTGTGATATGGTCCA CCGTCCTCCAGCCATGAGCCAGGCCTGTAACACAGAGCCCTGTCCCCCCAGGTGGCATGTGGGCTCTT GGGGGCCCTGCTCAGCTACCTGTGGAGTTGGAATTCAGACCCGAGATGTGTACTGCCTGCACCCAGGG GAGACCCCTGCCCCTCCTGAGGAGTGCCGAGATGAAAAGCCCCATGCTTTACAAGCATGCAATCAGTT TGACTGCCCTCCTGGCTGGCACATTGAAGAATGGCAGCAGTGTTCCAGGACTTGTGGCGGGGGAACTC AGAACAGAAGAGTCACCTGTCGGCAGCTGCTAACGGATGGCAGCTTTTTGAATCTCTCAGATGAATTG TGCCAAGGACCCAAGGCATCGTCTCACAAGTCCTGTGCCAGGACAGACTGTCCTCCACATTTAGCTGT GGGAGACTGGTCGAAGTGTTCTGTCAGTTGTGGTGTTGGAATCCAGAGAAGAAAGCAGGTGTGTCAAA GGCTGGCAGCCAAAGGTCGGCGCATCCCCCTCAGTGAGATGATGTGCAGGGATCTACCAGGGTTCCCT ^!CTTGTAAGATCTTGCCAGATGCCTGAGTGCAGTAAAATCAAATCAGAGATGAAGACAAAACTTGGTGA IGCAGGGTCCGCAGATCCTCAGTGTCCAGAGAGTCTACATTCAGACAAGGGAAGAGAAGCGTATTAACC TGACCATTGGTAGCAGAGCCTATTTGCTGCCCAACACATCCGTGATTATTAAGTGCCCAGTGCGACGA TTCCAGAAATCTCTGATCCAGTGGGAGAAGGATGGCCGTTGCCTGCAGAACTCCAAACGGCTTGGCAT CACCAAGTCAGGCTCACTAAAAATCCACGGTCTTGCTGCCCCCGACATCGGCGTGTACCGGTGCATTG CAGGCTCTGCACAGGAAACAGTTGTGCTCAAGCTCATTGGTACTGACAACCGGCTCATCGCACGCCCA GCCCTCAGGGAGCCTATGAGGGAATATCCTGGGATGGACCACAGCGAAGCCAATAGTTTGGGAGTCAC ATGGCACAAAATGAGGCAAATGTGGAATAACAAAAATGACCTTTATCTGGATGATGACCACATTAGTA ACCAGCCTTTCTTGAGAGCTCTGTTAGGCCACTGCAGCAATTCTGCAGGAAGCACCAACTCCTGGGAG TTGAAGAATAAGCAGTTTGAAGCAGCAGTTAAACAAGGAGCATATAGCATGGATACAGCCCAGTTTGA TGAGCTGATAAGAAACATGAGTCAGCTCATGGAAACCGGAGAGGTCAGCGATGATCTTGCGTCCCAGC TGATATATCAGCTGGTGGCCGAATTAGCCAAGGCACAGCCAACACACATGCAGTGGCGGGGCATCCAG GAAGAGACACCTCCTGCTGCTCAGCTCAGAGGGGAAACAGGGAGTGTGTCCCAAAGCTCGCATGCAAA AAACTCAGGCAAGCTGACATTCAAGCCGAAAGGACCTGTTCTCATGAGGCAAAGCCAACCTCCCTCAA TTTCATTTAATAAAACAATAAATTCCAGGATTGGAAATACAGTATACATTACAAAAAGGACAGAGGTC ATCAATATACTGTGTGACCTTATTACCCCCAGTGAGGCCACATATACATGGACCAAGGATGGAACCTT GTTACAGCCCTCAGTAAAGTAAGTAAAATAAAAATGCAGTATTCATTTTTGCAAAA

NOVl lg, CG50513-06 SEQ ID NO: 96 926 aa MW at 104117.1kD Protein Sequence

MADFIFKTRYTAAKDSWQFFFYQPISHQ RQTDFFPCTVTCGGGYQLNSAECVDIRLKRWPDHYCH YYPENVKP P LECSMDPCPSSDGFKEIMPYDHFQPLPRWEHNP TACSVSCGGGIQRRSFVCVEΞS ffiGEILQ EE C YAPKPKMQTC LFDCPK IA E SQCVTCG GLRYRVVCINHRGEHVGGC PQLKLHIKEECVIPIPCYKPKEKSPVEAKLP LKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQ VREVKCRVLLTFTQTETΞLPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSΞTTYDWEYAGF TPCTATCVGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPRWHVGS GPCSATCGV GIQTRDVYCLHPGETPAPPEECRDE PHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQNRRVTCRQL LTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGDWSKCSVSCGVGIQRRKQVCQRLAAGRRIP LSEMMCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQILSVQRVYIQTREEKRINLTIGSRAYLL PNTSVIIKCPVRRFQKSLIQWΞ DGRCLQNSKRLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETWL X,IGTDNRLIARPALREPMREYPGMDHSEANSLGVTVraKMRQMNNNDLYLDDDHISNQPFLRALLG HCSNSAGSTNS ELNKQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELA KAQPTHMQ RGIQEETPPAAQLRGETGSVSQSSHANSGKLTFKPKGPVLMRQSQPPSISFNTINSR IGNTVYITKRTEVINILCDLITPSEATYT TKDGTLLQPSVK

NOV1 lh, CG50513-07 SEQ ID NO: 97 1377 bp

DNA Sequence RF Start aTr jORF Stop: end of sequence

TGGGAACATAATCCTTGGACTGCATGTTCCGTGTCCTGTGGAGGAGGGATTCAGAGACGGAGCTTTGT GTGTGTAGAGGAATCCATGCATGGAGAGATATTGCAGGTGGAAGAATGGAAGTGCATGTACGCACCCA AACCCAAGGTTATGCAAACTTGTAATCTGTTTGATTGCCCCAAGTGGATTGCCATGGAGTGGTCTCAG TGCACAGTGACTTGTGGCCGAGGGTTACGGTACCGGGTTGTTCTGTGTATTAACCACCGCGGAGAGCA TGTTGGGGGCTGCAATCCACAACTGAAGTTACACATCAAAGAAGAATGTGTCATTCCCATCCCGTGTT ATAAACCAAAAGAAAAAAGTCCAGTGGAAGCAAAATTGCCTTGGCTGAAACAAGCACAAGAACTAGAA GAGACCAGAATAGCAACAGAAGAACCAACGTTCATTCCAGAACCCTGGTCAGCCTGCAGTACCACGTG TGGGCCGGGTGTGCAGGTCCGTGAGGTGAAGTGCCGTGTGCTCCTCACATTCACGCAGACCGAGACTG AGCTGCCCGAGGAAGAGTGTGAAGGCCCCAAGCTGCCCACCGAACGGCCCTGCCTCCTGGAAGCATGT GATGAGAGCCCGGCCTCCCGAGAGCTAGACATCCCTCTCCCTGAGGACAGTGAGACGACTTACGACTG GGAGTACGCTGGGTTCACCCCTTGCACAGCAACATGCGTGGGAGGCCATCAAGAAGCCATAGCAGTGT GCTTACATATCCAGACCCAGCAGACAGTCAATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCC ATGAGCCAGGCCTGTAACACAGAGCCCTGTCCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTC AGCTACCTGTGGAGTTGGAATTCAGACCCGAGATGTGTACTGCCTGCACCCAGGGGAGACCCCTGCCC CTCCTGAGGAGTGCCGAGATGAAAAGCCCCATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCT GGCTGGCACATTGAAGAATGGCAGCAGTGTTCCAGGACTTGTGGCGGGGGAACTCAGAACAGAAGAGT CACCTGTCGGCAGCTGCTAACGGATGGCAGCTTTTTGAATCTCTCAGATGAATTGTGCCAAGGACCCA AGGCATCGTCTCACAAGTCCTGTGCCAGGACAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCG AAGTGTTCTGTCAGTTGTGGTGTTGGAATCCAGAGAAGAAAGCAGGTGTGTCAAAGGCTGGCAGCCAA AGGTCGGCGCATCTCCCTCAGTGAGATGATGTGCAGGGATCTACCAGGGCTCCCTCTTGTAAGATCTT GCCAGATGCCTGAGTGC

NOVl lh, CG50513-07 SEQ ID NO: 98 459 aa MW at 51217.0kD Protein Sequence EHNPWTACSVSCGGGIQRRSFVCVEΞSMHGEILQVEE CMYAPKPKVMQTCNLFDCPKWIAME SQ CTVTCGRGLRYRWLCINHRGEHVGGCNPQLKLHIKEECVIPIPCY P EKSPVEAKLP LKQAQELE ETRIATEEPTFIPEP SACSTTCGPGVQVREVKCRVLLTFTQTETELPEEECEGPKLPTERPCLLEAC DESPASRELDIPLPEDSETTYDWEYAGFTPCTATCVGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPA MSQACNTEPCPPRHVGSWGPCSATCGVGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPP GHIEE QQCSRTCGGGTQNRRVTCRQLLTDGSFLNLSDELCQGP ASSHKSCARTDCPPHLAVGD S KCSVSCGVGIQRRKQVCQRLAAKGRRISLSEMMCRDLPGLPLVRSCQMPEC

NOVl li, 13376798 SNP for SEQ ID NO: J1598 bp SNP: position 58, T/A CG50513-01 99 DNA Sequence ORF Start: at ORF Stop: TGA at 1354 1

AAACAGCCACTTGTTTCATCCCACCTGGGCATTAGGTTGACTTCAAAGATGCCTCAGATACTGCAAAAC ATTAATGGGATCATCGAGGCCTTCAGGCGCTATGCAAGGACGGAGGGCAACTGCACAGCGCTCACCCGA GGGGAGCTGAAAAGACTCTTGGAGCAAGAGTTTGCCGATGTGATTGTGAAACCCCACGATCCAGCAACT GTGGATGAGGTCCTGCGTCTGCTGGATGAAGACCACACAGGGACTGTGGAATTCAAGGAATTCCTGGTC TTAGTGTTTAAAGTTGCCCAGGCCTGTTTCAAGACACTGAGCGAGAGTGCTGAGGGAGCCTGCGGCTCT CAAGAGTCTGGAAGCCTCCACTCTGGGGCCTCGCAGGAGCTGGGCGAAGGACAGAGAAGTGGCACTGAA GTGGGAAGGGCGGGGAAAGGGCAGCATTATGAGGGGAGCAGCCACAGACAGAGCCAGCAGGGTTCCAGA GGGCAGAACAGGCCTGGGGTTCAGACCCAGGGTCAGGCCACTGGCTCTGCGTGGGTCAGCAGCTATGAC AGGCAAGCTGAGTCCCAGAGCCAGGAAAGAATAAGCCCGCAGATACAACTCTCTGGGCAGACAGAGCAG ACCCAGAAAGCTGGAGAAGGCAAGAGGAATCAGACAACAGAGATGAGGCCAGAGAGACAGCCACAGACC AGGGAACAGGACAGAGCCCACCAGACAGGTGAGACTGTGACTGGATCTGGAACTCAGACCCAGGCAGGT GCCACCCAGACTGTGGAGCAGGACAGCAGCCACCAGACAGGAAGCACCAGCACCCAGACACAGGAGTCC ACCAATGGCCAGAACAGAGGGACTGAGATCCACGGTCAAGGCAGGAGCCAGACCAGCCAGGCTGTGACA GGAGGACACACTCAGATACAGGCAGGGTCACACACCGAGACTGTGGAGCAGGACAGAAGCCAAACTGTA AGCCACGGAGGGGCTAGAGAACAGGGACAGACCCAGACGCAGCCAGGCAGTGGTCAAAGATGGATGCAA GTGAGCAACCCTGAGGCAGGAGAGACAGTACCGGGAGGACAGGCCCAGACTGGGGCAAGCACTGAGTCA GGAAGGCAGGAGTGGAGCAGCACTCACCCAAGGCGCTGTGTGACAGAAGGGCAGGGAGACAGACAGCCC ACAGTGGTTGGTGAGGAATGGGTTGATGACCACTCAAGGGAGACAGTGATCCTCAGGCTGGACCAGGGC AACTTGCATACCAGTGTTTCCTCAGCACAGGGCCAGGATGCAGCCCAGTCAGAAGAGAAGCGAGGCATC ACAGCTAGAGAGCTGTATTCCTACTTGAGAAGCACCAAGCCATGACTTCCCCGACTCCAATGTCCAGTA

CTGGAAGAAGACAGCTGGAGAGAGTTTGGCTTGTCCTGCATGGCCAATCCAGTGGGTGCATCCCTGGAC

ATCAGCTCTTCATTATGCAGCTTCCCTTTTAGGTCTTTCTCAATGAGATAATTTCTGCAAGGAGCTTTC

TATCCTGAACTCTTCTTTCTTACCTGCTTTGCGGTGCAGACCCTCTCAGGAGCAGGAAGACTCAGAACA

AGTCACCCCTT

NOVlli, 13376798 SNP for SEQ ID NO: 451 aa ISNP: Leu to lie at CG50513-01 100 (position 20 Protein Sequence

KQPLVSSHLGIRLTS MPQILQNINGIIEAFRRYARTEGNCTALTRGELKRLLEQEFADVIVKPHDPAT VDEVLRLLDEDHTGTVEFKEFLVLVFKVAQACFKTLSESAEGACGSQESGSLHSGASQELGEGQRSGTE VGRAGKGQHYEGSSHRQSQQGSRGQNRPGVQTQGQATGSAVSSYDRQAESQSQERISPQIQLSGQTEQ TQKAGEGKRNQTTEMRPERQPQTREQDRAHQTGETVTGSGTQTQAGATQTVEQDSSHQTGSTSTQTQES TNGQNRGTEIHGQGRSQTSQAVTGGHTQIQAGSHTETVEQDRSQTVSHGGAREQGQTQTQPGSGQRWMQ VSNPEAGETVPGGQAQTGASTESGRQEWSSTHPRRCVTEGQGDRQPTVVGEE VDDHSRETVILRLDQG NLHTSVSSAQGQDAAQSEE RGITARELYSYLRSTKP

NOVllj, 13376799 SNP for SEQ ID NO: 1598 bp, SNP: T/C at position

CG50513-01 101 1516

DNA Sequence ORF Start: at 1 ORF Stop: TGA at 1354 lAAACAGCCACTTGTTTCATCCCACCTGGGCATTAGGTTGACTTCAAAGATGCCTCAGTTACTGCAAAAC ATTAATGGGATCATCGAGGCCTTCAGGCGCTATGCAAGGACGGAGGGCAACTGCACAGCGCTCACCCGA GGGGAGCTGAAAAGACTCTTGGAGCAAGAGTTTGCCGATGTGATTGTGAAACCCCACGATCCAGCAACT GTGGATGAGGTCCTGCGTCTGCTGGATGAAGACCACACAGGGACTGTGGAATTCAAGGAATTCCTGGTC TTAGTGTTTAAAGTTGCCCAGGCCTGTTTCAAGACACTGAGCGAGAGTGCTGAGGGAGCCTGCGGCTCT CAAGAGTCTGGAAGCCTCCACTCTGGGGCCTCGCAGGAGCTGGGCGAAGGACAGAGAAGTGGCACTGAA GTGGGAAGGGCGGGGAAAGGGCAGCATTATGAGGGGAGCAGCCACAGACAGAGCCAGCAGGGTTCCAGA GGGCAGAACAGGCCTGGGGTTCAGACCCAGGGTCAGGCCACTGGCTCTGCGTGGGTCAGCAGCTATGAC AGGCAAGCTGAGTCCCAGAGCCAGGAAAGAATAAGCCCGCAGATACAACTCTCTGGGCAGACAGAGCAG ACCCAGAAAGCTGGAGAAGGCAAGAGGAATCAGACAACAGAGATGAGGCCAGAGAGACAGCCACAGACC AGGGAACAGGACAGAGCCCACCAGACAGGTGAGACTGTGACTGGATCTGGAACTCAGACCCAGGCAGGT GCCACCCAGACTGTGGAGCAGGACAGCAGCCACCAGACAGGAAGCACCAGCACCCAGACACAGGAGTCC ACCAATGGCCAGAACAGAGGGACTGAGATCCACGGTCAAGGCAGGAGCCAGACCAGCCAGGCTGTGACA GGAGGACACACTCAGATACAGGCAGGGTCACACACCGAGACTGTGGAGCAGGACAGAAGCCAAACTGTA AGCCACGGAGGGGCTAGAGAACAGGGACAGACCCAGACGCAGCCAGGCAGTGGTCAAAGATGGATGCAA GTGAGCAACCCTGAGGCAGGAGAGACAGTACCGGGAGGACAGGCCCAGACTGGGGCAAGCACTGAGTCA GGAAGGCAGGAGTGGAGCAGCACTCACCCAAGGCGCTGTGTGACAGAAGGGCAGGGAGACAGACAGCCC ACAGTGGTTGGTGAGGAATGGGTTGATGACCACTCAAGGGAGACAGTGATCCTCAGGCTGGACCAGGGC AACTTGCATACCAGTGTTTCCTCAGCACAGGGCCAGGATGCAGCCCAGTCAGAAGAGAAGCGAGGCATC ACAGCTAGAGAGCTGTATTCCTACTTGAGAAGCACCAAGCCATGACTTCCCCGACTCCAATGTCCAGTA

CTGGAAGAAGACAGCTGGAGAGAGTTTGGCTTGTCCTGCATGGCCAATCCAGTGGGTGCATCCCTGGAC

ATCAGCTCTTCATTATGCAGCTTCCCTTTTAGGTCTTTCTCAATGAGATAATTTCTGCAAGGAGCTCTC iTATCCTGAACTCTTCTTTCTTACCTGCTTTGCGGTGCAGACCCTCTCAGGAGCAGGAAGACTCAGAACA

AGTCACCCCTT

NOVl lj, 13376799 SNP for SEQ ID NO: 102 451 aa SNP: not in coding region

CG50513-01

Protein Sequence QPLVSSHLGIRLTSKMPQLLQNINGIIEAFRRYARTEGNCTALTRGELKRLLEQEFADVIVKPHDPAT VDEVLRLLDEDHTGTVΞFKEFLVLVFKVAQACFKTLSESAEGACGSQESGSLHSGASQELGEGQRSGTE VGRAGKGQHYEGSSHRQSQQGSRGQNRPGVQTQGQATGSAWVSSYDRQAESQSQERISPQIQLSGQTEQ TQKAGEGKRNQTTEMRPERQPQTREQDRAHQTGETVTGSGTQTQAGATQTVEQDSSHQTGSTSTQTQES TNGQNRGTEIHGQGRSQTSQAVTGGHTQIQAGSHTETVEQDRSQTVSHGGAREQGQTQTQPGSGQRWMQ VSNPEAGETVPGGQAQTGASTESGRQE SSTHPRRCVTEGQGDRQPTVVGEE VDDHSRETVILRLDQG NLHTSVSSAQGQDAAQSEEKRGITARELYSYLRSTKP

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 1 IB.

Table 11B. Comparison of the NOV11 protein sequences.

NOVlla

NOVllb

NOVllc

NOVlld

NOVlle MAS TSP VLIGMVFMHSPLPQTTAEKSPGAYFLPEFALSPQGSFLEDTTGEQFLTYRY

NOVllf

NOVllg

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld

NOVlle DDQTSRNTRSDEDKDGN DA GD SDCSRTCGGGASYSLRRCLTGRNCEGQNIRYKTCSN

NOVllf

NOVllg NOVllh

NOVlla

NOVllb

NOVllc

NOVlld

NOVlle HDCPPDAEDFRAQQCSAYNDVQYQGHYYE LPRYNDPAAPCALKCHAQGQNLWELAPKV

NOVllf

NOVllg

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld

NOVlle LDGTRCNTDSLDMCISGICQAVGCDRQLGSNAKEDNCGVCAGDGSTCRLVRGQSKSHVSP

NOVllf

NOVllg

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld

NOVlle EKREENVIAVPLGSRSVRITVKGPAHLFIESKTLQGSKGEHSFNSPGVFWENTTVEFQR

NOVllf

NOVllg

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld

NOVlle GSERQTFKIPGPLMADFIFKTRYTAAKDSVVQFFFYQPISHQ RQTDFFPCTVTCGGGYQ

NOVllf

NOVllg -MADFI FKTRYTAAKDSWQFFFYQPISHQ RQTDFFPCTVTCGGGYQ NOVllh

NOVlla NOVllb NOVllc NOVlld MPYDHFQPLP NOVlle LNSAECVDIRLKRWPDHYCHYYPENVKPKPKLKECSMDPCPSSDGFKEIMPYDHFQPLP NOVllf MPYDHFQPLP NOVllg LNSAECVDIRLKRVVPDHYCHYYPENVKPKPKLKECS DPCPSSDGFKEIMPYDHFQPLP NOVllh

NOVlla NOVllb NOVllc NOVlld RWEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEE KCMYAPKPKVMQTCNLFDCP NOVlle RWEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEEWKCMYAPKPKVMQTCNLFDCP NOVllf RWEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEEWKCMYAPKPKVMQTCNLFDCP NOVllg R EHNP T AC S VS CGGGI QRRS FVCVEESMHGE I LQVEE KCMYAPKPKVMQTCNLFDC P NOVllh -WEHNP TACSVSCGGGIQRRSFVCVEESMHGEILQVEE KCMYAPKPKVMQTCNLFDCP

NOVlla NOVllb

NOVllc

NOVlld K IAMEWSQCTVTCGRGLRYRWLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK

NOVlle K IAMEWSQCTVTCGRGLRYRVVLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK

NOVllf KWIAME SQCTVTCGRGLRYRVVLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK

NOVllg K IAME SQCTVTCGRGLRYRWLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK

NOVllh KWIAME SQCTVTCGRGLRYRVVLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK

NOVlla KQPLVSSHLGIRLTSKMPQLLQNINGIIEAFRRYARTEGNCTALTRGEL

NOVllb TGSLLQNINGIIEAFRRYARTEGNCTALTRGEL

NOVllc

NOVlld SPVEAKLPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT

NOVlle SPVEAKLP LKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT

NOVllf SPVEAKLPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT

NOVllg SPVEAKLPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT

NOVllh SPVEAKLP LKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT

NOVlla KRLLEQEFADVIVKPHDPATVDEVLRLLDEDHTGTVEFKEFLVLVFKVAQACFKTLSESA

NOVllb KRLLEQEFADVIVKLEG

NOVllc

NOVlld ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYDWEYAGFTPCTATC

NOVlle ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYD EYAGFTPCTATC

NOVllf ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYD EYAGFTPCTATC

NOVllg ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYD EYAGFTPCTATC

NOVllh ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYDWEYAGFTPCTATC

NOVlla EGACGSQESGSLHSGASQELGEGQRSGTEVGRAGKGQHYEGSSHRQSQQGSRGQNRPGVQ

NOVllb

NOVllc VNDSLCDMVHRPPAMSQACNTEPCPPR HVGS GPCSATCG

NOVlld VGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPRWHVGS GPCSATCG

NOVlle VGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPR HVGS GPCSATCG

NOVllf VGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPRWHVGS GPCSATCG

NOVllg VGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPRWHVGS GPCSATCG

NOVllh VGGHQEAIAVCLHIQTQQTVNDSLCD VHRPPAMSQACNTEPCPPRWHVGS GPCSATCG

NOVlla TQGQATGSA VSSYDRQAESQSQERISPQIQLSGQTEQTQKAGEGKRNQTTEMRPERQPQ

NOVllb

NOVllc VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQ

NOVlld VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQ

NOVlle VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPG HIEE QQCSRTCGGGTQ

NOVllf VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPG HIEE QQCSRTCGGGTQ

NOVllg VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPG HIEE QQCSRTCGGGTQ

NOVllh VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPG HIEE QQCSRTCGGGTQ

NOVlla TREQDRAHQTGETVTGSGTQTQAGATQTVEQDSSHQTGSTSTQTQESTNGQNRGTEIHGQ

NOVllb

NOVllc NR RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGDWSKCSVSCGV

NOVlld NR RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGD SKCSVSCGV

NOVlle NR RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGD S CSVSCGV

NOVllf NR RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGD SKCSVSCGV

NOVllg NR RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGD SKCSVSCGV

NOVllh NR RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGD SKCSVSCGV

NOVlla GRSQTSQAVTGGHTQIQAGSHTETVEQDRSQTVSHGGAREQGQTQTQPGSGQRMQVSNP

NOVllb

NOVllc GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQ

NOVlld GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQ NOVlle GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQ

NOVllf GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGLPLVRSCQ PECSKIKSEMKTKLGEQGPQ

NOVllg GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQ

NOVllh GIQRRKQVCQRLAAKGRRISLSEMMCRDLPGLPLVRSCQMPEC

NOVlla EAGETVPGGQAQTGASTESGRQE SSTHPRRCVTEGQGDRQPTVVGEEWVDDHSRETVIL

NOVllb

NOVllc ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQ EKDGRCLQNSK

NOVlld ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWEKDGRCLQNSK

NOVlle ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWEKDGRCLQNSK

NOVllf ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQ EKDGRCLQNSK

NOVllg ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQ EKDGRCLQNSK

NOVllh

NOVlla RLDQGNLHTSVSSAQGQDAAQSEEKRGITARELYSYLRSTKP

NOVllb

NOVllc RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETGVLKLIGTDNRLIARPTLXEPMREYPG

NOVlld RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETVVLKLIGTDNRLIARPALREPMREYPG

NOVlle RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETWLKLIGTDNRLIARPALREPMREYPG

NOVllf RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETVVLKLIGTDNRLIARPALREPMREYPG

NOVllg RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETVVLKLIGTDNRLIARPALREPMREYPG

NOVllh

NOVlla

NOVllb

NOVllc MDHNEANS

NOVlld MDHSEANSLGVT HKMRQMNNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNS ELKN

NOVlle MDHSEANSLGVT HKMRQMNNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNS ELKN

NOVllf MDHSEANSLGVTWHKMRQMNNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNS ELKN

NOVllg MDHSEANSLGVT HKMRQMNNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNS ELKN

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld KQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQ

NOVlle KQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQ

NOVllf KQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQ

NOVllg KQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQ

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld WRGIQEETPPAAQLRGETGSVSQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSR

NOVlle WRGIQEETPPAAQLRGETGSVSQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSR

NOVllf WRGIQEETPPAAQLRGETGSVSQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSR

NOVllg RGIQEETPPAAQLRGETGSVSQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSR

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld IGNTVYITKRTEVINILCDLITPSEATYT TKDGTLLQPSVKIILDGTGKIQIQNPTRKE

NOVlle IGNTVYITKRTEVINILCDLITPSEATYT TKDGTLLQPSVKIILDGTGKIQIQNPTRKE

NOVllf IGNTVYITKRTEVINILCDLITPSEATYT TKDGTLLQPSVKIILDGTGKIQIQNPTRKE

NOVllg IGNTVYITKRTEVINILCDLITPSEATYT TKDGTLLQPSVK NOVllh

NOVlla

NOVllb

NOVllc

NOVlld QGIYECSVANHLGSDVESSSVLYAEAPVILSVERNITKPEHNHLSVWGGIVEAALGANV

NOVlle QGIYECSVANHLGSDVESSSVLYAEAPVILSVERNITKPEHNHLSVWGGIVEAALGANV

NOVllf QGIYECSVANHLGSDVESSSVLYAEAPVILSVERNITKPEHNHLSVVVGGIVEAALGANV

NOVllg

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld TIRCPVKGVPQPNIT LKRGGSLSGNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAV

NOVlle TIRCPVKGVPQPNIT LKRGGSLSGNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAV

NOVllf TIRCPVKGVPQPNIT LKRGGSLSGNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAV

NOVllg

NOVllh

NOVlla

NOVllb

NOVllc .

NOVlld ATSVLHLLERR PESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPFWEPGN SHCS

NOVlle ATSVFHLLERRWPESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPF EPGN SHCS

NOVllf ATSVLHLLERR PESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPFWEPGNWSHCS

NOVllg

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld ATCGHLGARIQRPQCVMANGQEVSEALCDHLQKPLAGFEPCNIRDCPARWFTSVWSQCSV

NOVlle ATCGHLGARIQRPQCVMANGQEVSEALCDHLQKPLAGFEPCNIRDCPAR FTSVWSQCSV

NOVllf ATCGHLGARIQRPQCVMANGQEVSEALCDHLQ PLAGFEPCNIRDCPAR FTSV SQCSV

NOVllg

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld SCGEGYHSRQVTCKRTKANGTVQVVSPRACAPKDRPLGRKPCFGHPCVQWEPGNRCPGRC

NOVlle SCGEGYHSRQVTCKRTKANGTVQWSPRACAPKDRPLGRKPCFGHPCVQ EPGNRCPGRC

NOVllf SCGEGYHSRQVTCKRTKANGTVQWSPRACAPKDRPLGRKPCFGHPCVQWEPGNRCPGRC

NOVllg

NOVllh

NOVlla

NOVllb

NOVllc

NOVlld MGRAVRMQQRHTACQHNSSDSNCDDRKRPTLRRNCTSGACDVC HTGP KPCTAACGRGF

NOVlle MGRAVRMQQRHTACQHNSSDSNCDDRKRPTLRRNCTSGACDVCWHTGPWKPCTAACGRGF

NOVllf MGRAVRMQQRHTACQHNSSDSNCDDRKRPTLRRNCTSGACDVC HTGP KPCTAACGRGF

NOVllg

NOVllh

NOVlla NOVllb

NOVllc

NOVlld QSRKVDCIHTRSCKPVAKRHCVQKKKPIS RHCLGPSCDRDCTDTTHYCMFVKHLNLCSL

NOVlle QSRKVDCIHTRSCKPVAKRHCVQKKKPIS RHCLGPSCDRDCTDTTHYCMFVKHLNLCSL

NOVllf QSRKVDCIHTRSCKPVAKRHCVQKKKPIS RHCLGPSCDRDCTDTTHYCMFVKHLNLCSL

NOVllg

NOVllh

NOVlla NOVllb NOVllc NOVlld DRYKQRCCQSCQEG NOVlle DRYKQRCCQSCQEG NOVllf DRYKQRCCQSCQEG NOVllg NOVllh

NOVlla (SEQ ID NO 84) NOVllb (SEQ ID NO 86) NOVllc (SEQ ID NO 88) NOVlld (SEQ ID NO 90) NOVlle (SEQ ID NO 92) NOVllf (SEQ ID NO 94) NOVllg (SEQ ID NO 96) NOVllh (SEQ ID NO 98)

Further analysis of the NO VI la protein yielded the following properties shown in Table l lC.

Table 11C. Protein Sequence Properties NOVlla

SignalP analysis: No Known Signal Sequence Predicted

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 1; pos.chg 1; neg.chg 0 H-region: length 10; peak value 5.49 PSG score: 1.09

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -10.00 possible cleavage site: between 26 and 27

>» Seems to have no N-terminal signal peptide

Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 0.63 (at 90) ALOM score: 0.63 (number of TMSs: 0)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 6 Charge difference: 0.5 C( 2.5) - N( 2.0) C > N: C-terminal side will be inside

>»Caution: Inconsistent mtop result with signal peptide MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75): 5.65 Hyd Moment (95) : 4.29 G content: 2 D/E content: 1 S/T content: 4 Score: -4.11

Gavel: prediction of cleavage sites for mitochondrial preseq R-3 motif at 35 FRRY|A

NUCDISC: discrimination of nuclear localization signals pat4: none pat7 : none bipartite: none content of basic residues: 10.0% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals:

KKXX-like motif in the C-terminus: RSTK

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: found RLTSKMPQL at 12 VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

COIL: Lupas' s algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23) :

73.9 %: nuclear

13.0 % : mitochondrial

13.0 %: cytoplasmic

» prediction for CG50513-01 is nuc (k=23)

A search of the NO VI la protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1 ID.

In a BLAST search of public sequence databases, the NO VI la protein was found to have homology to the proteins shown in the BLASTP data in Table 1 IE.

PFam analysis predicts that the NO VI la protein contains the domains shown in the Table 1 IF.

Example 12.

The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12 A.

Table 12A. NOV12 Sequence Analysis OV12a, CG50949-03 SEQ ID NO: 103 2432 bp DNA Sequence ORF Start: ATG at 112 ORF Stop: TAG at 1870

GGACACTGACATGGACTGAAGGAGTAGAAAACATGCCTGAGAAGCCAGGGGCCAAGATGGATCTTCTC CTCGACATCAGCTAAGCCTGGAGGACTCTCCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATG

CATCTCCAGCAAGAACACCTTCAGCTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCA GGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGC ATCTCCAGCCCAGGCATCTCCAGCTGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAG CCCAGGCATCTCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCC TCATCCGGCAGGTCATCATCCGCCAGGTCGGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGT TAGAGCAACACCAGTGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGG CCACCAGGGAGAGCCCAGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCG CTCATCGGGTGCGTGCTCCTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCA GGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACG GGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTG CTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTA CTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGG ATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAA TGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGAT CGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCC ACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACC CGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGC AGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACATCGCCC TCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGA CAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAA GACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTTGG TCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGC CAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAG CTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCT GGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCC TCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGTAGGCAGAGGTCCCCTCAGCGTCCCCATATTCGGG GGGTGTTCTGGACAGGGTCAAATGTGATGCCTGGGGTCAATCCCAGCTGTCTGTGTTTCTTTCCCTGC

TTTTCTTCCCTCAGAACAGAGCTCAGCGGGTTGAAAAAGGGTGGACCTACAGGCCAGGCAGGCAGTTG

CTGGGCAGATGTTCTCCCAGAAGTATTTTTTTGTGTAAGGTTGCAATGGACTTTGAAAACGTTTCAGT

TTCTGCAGAGGATTTTGTGATAGTCTTTGTTATCAAGCATTTATGCATGGGAATCCGCTCTTCATGGC

CTTTCCCAGCTCTGTTTGTTTTAGTCTTTTTGATTTTCTTTTTGTTGTTGTTGTTGTCTTTTTTTAAA

AACACAAGTGACTCCATTTTAACTCTGACAACTTTCACAGCTGTCACCAGAATGCTCCCTGAGAACTA

CCATTCTTTCCCTTTCCCACTTAAAATATTTCATCAGAACCTCACCACTATCATAAAAGAGTATAAAG

TAATAAAATAATAAAAAGCGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

NOV12a, CG50949-03 SEQ ID NO: 104 586 aa MW at 63152.3kD Protein Sequence

MERDSHGNAS PARTP SAGAS PAQAS PAGTPPGRAS PAQAS PAQAS PAGTPPGRAS PAQAS PAGTPPGR ASPGRASPAQASPAQASPARASPAXiASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSP ARSAPATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALWSLIILFQFWQGHTGIRYKEQRESC PKi VRCDGVVDC LKSDELGCVRFD DKSLLKIYSGSSHQ LPICSSNWNDSYSEKTCQQLGFESAH RTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK P Q VSLHFGTTHI CGGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAAS I AE 11 INSNYTD EEDDYDIALMRLSKPLTLSAHIHPACLP HGQTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLID FKKCNDYLλTϊυSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS GTGCGQRNKPGVY TKVTEVLP IYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRV

NOV12b, 197192399 SEQ ID NO: 105 717 bp DNA Sequence ORF Start: at 1 JORF Stop: end of sequence

TCCCTGTGGATTGGATCCATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCA&GTGAG TCTGCACTTCGGTACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCG CCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAAC CTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGA GGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTG CTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAG ACCAGGGAGACAGATGACAAGACATCCCCCTCCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAA GAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTC GTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG TACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAA AGTGACAGAAGTTCTTCCCTGGATTTACAGCCTCGAG

NOV12b, 197192399 SEQ ID NO: 106 239 aa MW at 26529.8kD Protein Sequence

SLWIGSIVGGAIΛSDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGK TRETDDKTSPSLREVQVNLIDFK CNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS GTGCGQRNKPGVYT VTEVLP IYSLE

NOV12c, 257499999 SEQ ID NO: 107 717 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

TCCCTGTGGATTGGATCCATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAG TCTGCACTTCGGTACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCG CCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAAC CTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGA GGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTG CTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAG ACCAGGGAGACAGATGACAAGACATCCCCCTCCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAA GAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTC GTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG TACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAA AGTGACAGAAGTTCTTCCCTGGATTTACAGCCTCGAG

NOV12c, 257499999 SEQ ID NO: 108 239 aa MW at 26529.8kD Protein Sequence

SL IGSIVGGALASDSK P QVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREICVLEGWKVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACIiPMHGQTFSLNETCWITGFGK TRETDDKTSPSLREVQVNLIDFI CNDYLVYDSYLTPR MCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSLE

NOV12d, 257450010 SEQ ID NO: 109 1101 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

GGATCCACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGG GGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGC TTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTAC TCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCT CCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATA GCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGAC GCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAA GGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCA ACAGCAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACC CTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTG CTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGC AGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGG ATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGT CTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAA ACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGA TCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACC CAGGGTGCTCGAG

NOV12d, 257450010 SEQ ID NO: 110 367 aa MW at 40822.7kD Protein Sequence

GSTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFD DKSLLKIYSGSSHQWLPICSSNWNDSY SEKTCQQLGFERSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK P QVSLHFGTTHICGGTLID AQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAAS I AE 11 INSNYTDEEDDYDI ALMRLSKPLT LSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDD TSPFLREVQVNLIDFKKCNDYLVYDSYLTPR ^MCAGDL GGRDSCQGDSGGP VCEQNNR G TS G GCGQ NKPGVYT V EVLPWI SKME SLQQDTAPSRLGTSSGGDPGGAPRVLE NOV12e, 252417780 SEQ ID NO: 111 1203 bp DNA Sequence ORF Start: at ORF Stop: end of sequence

ACCGGATCCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCT

GTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAG

TCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGA

CTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCC

ACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGG

TCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGG

GCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCA

CCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTC

GTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCC

TGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACA

TCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATG

CATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGA

TGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACT

ACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGAC

TCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGT

CACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTC

TTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGA

ACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC

NOV12e, 252417780 SEQ ID NO: 112 401 aa MW at 44688.8kD Protein Sequence

TGSHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDWDKSLLKIYSGSSHQ LPICSSNWND SYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTG RIVGGALASDS P QVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNIiHQLP EAASIAE11INSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLP HGQTFS NETCWITGFGKTRETD DKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGV TS GTGCGQRNKPGVYTKVTEVLP IYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG

NOV12f, 252417791 SEQ ID NO: 113 l llO bp DNA Sequence ORF Start: at 2 jORF Stop: end of sequence

ACCGGATCCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCT

GTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAG

TCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGA

CTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGGTCTGAATGCCCTTCCCAGCGGTATA

TCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCC

TCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCT

CATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGG

GCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATC

ATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCC

CCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATG

AGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGG

GAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTAC

CCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGC

CTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGC

CAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGA

GGTAAGATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAG

GAGCACCCAGGGTGCTCGAGGGC

NOV12f, 252417791 SEQ ID NO: 114 370 aa |MW at 41118.0kD Protein Sequence

TGSHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWND SYSEKTCQQLGFERSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWP QVSLHFGTTHICGGTL IDAQWVLTAAHCFFVTREKVLEG VYAG SNLHQLPEAASIAE11INSNYTDEEDDYDIALMRLSKP LTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLT PRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTSWGTGCGQRlvTKPGVYTKVTEVLPWIYSKME VRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12g, 252417821 SEQ ID NO: 115 1203 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence

ACCGGATCCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCT

GTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAG

TCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGA

CTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCC

ACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGG

TCTGAATGCCCTTTCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGG

GCGGATCGTGGGAGGGGCGCTGGTCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCA

CCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTC

GTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCC

TGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACA

TCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATG

CATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGA

TGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACT

ACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGAC

TCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGT

CACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTC

TTCCCTGGATTTACAGCAAGATGGAGGTAAAATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGA

ACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC

NOV12g, 252417821 SEQ ID NO: 116 401 aa MW at 44749. OkD Protein Sequence

TGSHTGIRYKEQRESCPIOLAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQ LPICSSNND SYSEKTCQQLGFΞSAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPFQRYISLQCSHCGLRA TG RIVGGALVSDSKWP QVSLHFGTTHICGGTLIDAQ VLTAAHCFFVTREKVLΞG KVYAGTSNLHQLP EAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETD DKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPR CAGDLRGGRDSCQGDSGGPLVCEQNi YLAGV TS GTGCGQRNKPGVYTKVTEVLP IYSKMEVKSLQQDTAPSRLGTSSGGDPGGAPRVLEG

NOV12h, 252417840 SEQ ID NO: 117 1203 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

ACCGGATCCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCT

GTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAG

TCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACAGGAATGA

CTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCC

ACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGG

TCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGG

GCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCA

CCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTC

GTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCC

TGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACA

TCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATG

CATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGA

TGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACT

ACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGAC

TCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGT

CACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTC

TTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGA

ACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC

NOV12h, 252417840 SEQ ID NO: 118 401 aa MW at 44658.8kD Protein Sequence

TGSHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDWDKS LKIYSGSSHQWLPICSSNRND SYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTG RIVGGALASDSK PWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLP EAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETD DKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPR MCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGV TSWGTGCGQRNKPGVYTKVTEVLP IYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG

NOV12i, 257474313 SEQ ID NO: 119 1779 bp

DNA Sequence JORF Start: at 1 lORF Stop: end of sequence

ACCGGATCCACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAGCTGGAG

CATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCA

GCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCTGGTAC

ACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAG

CCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGGTCATCATCCGCCAGGTCA

GCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAGTGGGGGCTGTACCCAT

CCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCCAGGTACGAGCCTGC

CCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTCCTCCTCATTGCC

CTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCA

GAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACG

AGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAG

TGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTT

CGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGAT

ACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG

TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAA

GTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCC

AGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTG

TACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAG

CAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGT

CCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGG

ATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGT

CAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGA

TGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGT

GAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAA

ACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCC

TGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGG

GTGCTCGAGGGC

NOV12i, 257474313 SEQ ID NO: 120 593 aa MW at 63798.0 D Protein Sequence

TGS MERDSHGNASPARTPSAGASPAQAS AGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGT PPGRAS GRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAV I RSSPARSAPATRATRESPGTSLPKFT REGQKQLPLIGCVLLLIALWSLIILFQF QGHTGIRYKEQ RESCPΗAVRCDGVVDCKLKSDELGCVRFD DKSLLKIYSGSSHQWLPICSSlvTWNDSYSEKTCQQLGF ESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK PWQVSLHFGTTHICGGTLIDAQ VLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINS NYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQV NLIDFKKC1VTDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWY1--AGVTS GTGCGQRNK PGVYTKVTEVLP IYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG

NOV12J, 257474324 SEQ ID NO: 121 1626 bp

DNA Sequence pRF Start: at 1 JORF Stop: end of sequence

ACCGGATCCACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAGCTGGAG

CATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCA

GCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCTGGTAC

ACCTCCAGGCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGGTCATCATCCG

CCAGGTCAGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAGTGGGGGCT

GTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCCAGGTAC

GAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTCCTCC

TCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTAC

AAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAA

GAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCT

CCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAG

CTGGGTTTCGAGAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACT GAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGA GTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCC GCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAA CCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGG AGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCT GCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAA GACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCA AGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTT CGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTG GTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCA AAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCA CCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC

NOV12J, 257474324 SEQ ID NO: 122 542 aa MW at 58367.2kD Protein Sequence

TGST ERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGT PPGRASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGT SLPKFTWREGQKQLPLIGCVLLLIALWSLIILFQF QGHTGIRYKEQRESCPKHAVRCDGWDCKLK SDELGCVRFDWDKSLLKIYSGSSHQ LPICSSNWNDSYSEKTCQQLGFERSECPSQRYISLQCSHCGL RAMTGRIVGGALASDSK P QVSLHFGTTHICGGTLIDAQ VLTAAHCFFVTREKVLEG KVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGK TRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG

NOV12k, CG50949-06 SEQ ID NO: 123 1780 bp

DNA Sequence ORF Start: ATG at 14 ORF Stop: end of sequence

CACCGGATCCACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAGCTGGAG

CATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCA GCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCTGGTAC ACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAG CCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGGTCATCATCCGCCAGGTCA GCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAGTGGGGGCTGTACCCAT CCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCCAGGTACGAGCCTGC CCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTCCTCCTCATTGCC CTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCA GAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACG AGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAG TGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTT CGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGAT ACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAA GTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCC AGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTG TACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAG CAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGT CCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGG ATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGT CAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGA TGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGT GAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAA ACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCC TGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGG GTG

NOV12k, CG50949-06 SEQ ID NO: 124 586 aa MW at 63152.3kD Protein Sequence

MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASP GTPPGRASPAQASPAGTPPGR ASPGRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSP ARSAPATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALWSLIILFQFWQGHTGIRYKEQRESC PKHAVRCDGWDCKLKSDELGCVRFD DKSLLKIYSGSSHQ LPICSSNWNDSYSEKTCQQLGFESAH RTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRA TGRIVGGALASDSKWPWQ :VSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEI IINSNYTD |EEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLID FKKCNDYLVYDSYLTPR^MCAGDLRGGRDSCQGDSGGPLVCEQNLSM YLAGVTS GTGCGQRNKPGVY KVTEVLP IYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRV

NOV121, 268669017 SEQ ID NO: 125 1218 bp

DNA Sequence ORF Start: at 1 [ORF Stop: end of sequence

ACCGGATCCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCA

AGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGG

TTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAG

CAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGA

CAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAG

GAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACT

GAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGA

GTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCC

GCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAA

CCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGG

AGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCT

GCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAA

GACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCA

AGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTT

CGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTG

GTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCA

AAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCA

CCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC

NOV121, 268669017 SEQ ID NO: 126 406 aa MW at 45335.5kD Protein Sequence

TGSQF QGHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDWDKSLLKIYSGSSHQ LPICS SNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGL RAMTGRIVGGAIASDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIAL RLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGK TRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG

[NOV12m, CG50949-05 SEQ ID NO: 127 2310 bp

DNA Sequence JORF Start: ATG at 88 (ORF StopTTAA at 1699

CGCCCGGGCAGGTTGAGAAGCCAGGGGCCAAGATGGATCTTCTCCTCGACATCAGCTAAGCCTGGAGG

ACTCTTCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAG

CTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCA TCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGC TGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCAGGCAT CTCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGC AGGTCATCATCCGCCAGGTCAGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAAC ACCAGTGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGG AGAGCCCAGTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCC AAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAG GTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTA GCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGG ACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCA GGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGAC TGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTG AGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGC CGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCA ACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAG GAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCC TGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCA AGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTC AAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCT TCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCT GGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACC AAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGAGCGAGGTGCGATTCAGAAAATCCTA ACCAGCTGGCCTGCTGCTCTGCACAGCACCGGCTGCTGTGAAGACTCTGGCCATGGTGACTGGCCATG TGTGGCATCATCTGGGCTAATGGCCACCGGGCACCATCAGACTCCCACCTCCACTGTCTGCTGCCTCT

GTGTGTGTGTGTGTGTGTGTGTGTGTGCATATGTGTGCATTGCCACTCTCCCAAGTTTTTCAGAAACC

AGCAGAGCTGTCAACTCTTCTCAAAATCCCAGGCTGGAAATTACCTGGAGACAAGAGTTGAGTACCGT

GGATGTTCCTACAGGAGTGTCCATAGATGGATGGAGGAGGTGGAGCCCAGAGCCCAAGGAAGAGCTGG

GAATTCTTGCTTCTCTGACCCTCACTTACAGACTAGCCCAGTGTGGGCAGATGCCAGCGGCCCAGGTG

GCGCCATTGCTGTCCTGGGATGGATCGTGGGTTTTGGTGGATGCAGCTTCCCAGGGCCTGGACCGTCT

TCGGTGAAAAGCTGCTCCCGTTGGCTTTATGAGCATCAAGTCCTCACCCAGACCCCCTGCTGGTGCCG

TGGATGTCACCAGTCGGACTGTGCTGTGGCTAACCAGGCTGACAACTGAGATGAGGATTCACTGTA

NOV12m, CG50949-05 SEQ ID NO: 128 537 aa MW at 58084.3kD Protein Sequence

MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGR ASPGRASPAQASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVP IRSSPARSAPATRATRESPVQF QGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKS LLKIYSGSSHQWLPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRS ECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK P QVSLHFGTTHICGGTLIDAQWVLTAAHCFFV TREKVLEG KVYAGTSNLHQLPEAASIAE11INSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMH GQTFSLNETC ITGFGKTRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDS CQGDSGGPLVCEQNNR YLAGVTS GTGCGQRNKPGVYTKVTEVLP IYSKMESEVRFRKS

NOV12n, 317431859 SEQ ID NO: 129 11707 bp

DNA Sequence JORF Start: at 1 JORF Stop: end of sequence

ACCGGATCCACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAGCTGGAG

CATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCA

GCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCTGGTAC

ACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGG

CTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGGTCATCATCCGCCAGGTCAGCCTCGGTGACAACC

TCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAGTGGGGGCTGTACCCATCCGATCATCTCCTGC

CAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCCAGGTACGAGCCTGCCCAAGTTCACCTGGC

GGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTCCTCCTCATTGCCCTGGTGGTTTCGCTC

ATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCC

CAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGA

GGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGT

AGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCG

GACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCC

AGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGA

CTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGT

GAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTG

CCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGC

AACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGA

GGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACC

CTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGC

AAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTT

CAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACC

TTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGC

TGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACAC

CAAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGAGCGAGGTGCGATTCAGAAAATCCC

TCGAGGGC

NOV12n, 317431859 SEQ ID NO: 130 569 aa MW at 61684.8kD Protein Sequence TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGT PPGRASPGRASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVP RSSPA RSAPATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALWSLIILFQFWQGHTGIRYKEQRESCP KHAVRCDGVVDCKLKSDELGCVRFD DKSLLKIYSGSSHQWLPICSSN NDSYSEKTCQQLGFESAHR TTEVAHRDFANSFSILRY STIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQV SLHFGTTHICGGTLIDAQ VLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDE EDDYDIALMRLSKPLTLSAHIHPACLP HGQTFSLNETC ITGFGKTRETDDKTSPFLREVQVNXilDF KKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS GTGCGQRNKPGVYT KVTEVLP IYSKMESEVRFRKSLEG

NOV12o, CG50949-01 SEQ ID NO: 131 1314 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 1264

ATGGAGAGCCCAGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCAT CGGGTGCGTGCTCCTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCC ACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTG GTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAA AATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAG AGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTT GCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCC TTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGG GAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATC TGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGA GAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCT CCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATG CGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGAC CTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACAT CCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTAT GACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGG AGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGG GCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCTGGATT TACAGCAAGATGGAGAGCGAGGTGCGATTCACAAAATCCTAACCAGCTGGCCTGCTGCTCTGCACAGC ACCGGCTGCTGTGAAGACTCTG

NOV12o, CG50949-01 SEQ ID NO: 132 421 aa MW at 47484.5kD Protein Sequence

MESPGTSLPKFTWREGQKQLPLIGCVLLLIALWSLIILFQF QGHTGIRYKEQRESCPKHAVRCDGV VDCKLKSDELGCVRFD DKSLLKIYSGSSHQWLPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDF ANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHI CGGTLIDAQ VLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEEDDYDIALM RLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQVNLIDFKKCNDYLVY DSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS GTGCGQRNKPGVYTKVTΞVLP I YSKMESEVRFTKS

NOV12p, CG50949-02 SEQ ID NO: 133 1146 bp

DNA Sequence JORF Start: at 1 ]ORF Stop: end of sequence

TTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGC TGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACT GGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAAC TGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGA GGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCC TCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCC ATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCA CTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACT GCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCAC CAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGA CTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCC TCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGG GAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATG CAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGG GCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTG GCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGAC AGAAGTTCTTCCCTGGATTTACAGCAAGATGGΛGAGCGAGGTGCGATTCACAAAATCC

NOV12p, CG50949-02 SEQ ID NO: 134 382 aa MW at 43224.3kD Protein Sequence

FQF QGHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDWDKSLLKIYSGSSHQ LPICSSN WNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRA MTGRIVGGAIΛSDSK P QVSLHFGTTHICGGTLIDAQ VLTAAHCFFVTREKVLEG KVYAGTSNLH QLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTR ETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRM CAGDLRGGRDSCQGDSGGPLVCEQNNR YL AGVTSWGTGCGQRNKPGVYTKVTEVLP IYSKMΞSEVRFTKS

NOV12q, CG50949-04 SEQ ID NO: 135 762 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

ATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGTACCAC CCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGA CCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAG GCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACATCGC CCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATG GACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGAC AAGACATCCCCCTCCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTT GGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCT GCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACC AGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCC CTGGATTTACAGC

NOV12q, CG50949-04 SEQ ID NO: 136 1231 aa MW at 25643.8kD Protein Sequence

IVGGALASDSK P QVSLHFGTTHICGGTLIDAQ VLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPΞ AASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDD KTSPSLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVT S GTGCGQRNKPGVYTKVTEVLP IYS

NOV12r, CG50949-07 SEQ ID NO: 137 1219 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

ACCGGATCCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCA

AGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGG

TTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAG

CAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGA

CAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAG

GAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACT

GAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGA

GTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCC

GCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAA

CCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGG

AGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCT

GCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAA

GACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCA

AGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTT

CGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTG

GTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCA

AAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCA

CCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC

NOV12r, CG50949-07 SEQ ID NO: 138 406 aa MW at 45335.5kD Protein Sequence TGSQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFD DKSLLKIYSGSSHQ LPICS SNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGL RAMTGRIVGGALASDSKWP QVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKΛπ^EG KVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGK TRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS GTGCGQRNKPGVYTKVTEVLP IYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG

NOV12s, 13374729 SNP for SEQ ID NO: 2432 bp SNP: position 902 A/C

CG50949-03 139

DNA Sequence ORF Start: ORF Stop: TAG at 1870 ATG at 112

GGACACTGACATGGACTGAAGGAGTAGAAAACATGCCTGAGAAGCCAGGGGCCAAGATGGATCTTCTCCT

CGACATCAGCTAAGCCTGGAGGACTCTCCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATGCATC

TCCAGCAAGAACACCTTCAGCTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGG GCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAG CCCAGGCATCTCCAGCTGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATC TCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGG TCATCATCCGCCAGGTCGGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAG TGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCC AGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTC CTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGT ACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAA GAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCC CATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCCGCAGCTGG GTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAG ATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGT GGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTG GGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCG GGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACA CCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACAT CCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTT GGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACT TCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCT TCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG TACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAG TGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAG CAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGTAGGCAGAGGTCCCCTCAGCG

TCCCCATATTCGGGGGGTGTTCTGGACAGGGTCAAATGTGATGCCTGGGGTCAATCCCAGCTGTCTGTGT

TTCTTTCCCTGCTTTTCTTCCCTCAGAACAGAGCTCAGCGGGTTGAAAAAGGGTGGACCTACAGGCCAGG

CAGGCAGTTGCTGGGCAGATGTTCTCCCAGAAGTATTTTTTTGTGTAAGGTTGCAATGGACTTTGAAAAC

GTTTCAGTTTCTGCAGAGGATTTTGTGATAGTCTTTGTTATCAAGCATTTATGCATGGGAATCCGCTCTT

CATGGCCTTTCCCAGCTCTGTTTGTTTTAGTCTTTTTGATTTTCTTTTTGTTGTTGTTGTTGTCTTTTTT

TAAAAACACAAGTGACTCCATTTTAACTCTGACAACTTTCACAGCTGTCACCAGAATGCTCCCTGAGAAC

TACCATTCTTTCCCTTTCCCACTTAAAATATTTCATCAGAACCTCACCACTATCATAAAAGAGTATAAAG

TAATAAAATAATAAAAAGCGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

NOV12s, 13374729 SNP for SEQ ID NO: 586 aa SNP: Gin to Pro at position

CG50949-03 140 264

Protein Sequence ERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGRAS PGRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSPARSA PATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALWSLIILFQFWQGHTGIRYKEQRESCPKHAVR CDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQ LPICSSNVINDSYSEKTCPQLGFESAHRTTEVAHR DFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRA TGRIVGGALASDSK P QVSLHFGTTHI CGGTLIDAQ VLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEEDDYDIALMRL SKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYL P MCAGD GG DSCQGDSGGPLVCEQ ^T Y AG S GTGCGQRNKPGV K E IYSKME RSLQQDTAPSRLGTSSGGDPGGAPRV

NOV12t, 13374730 SNP for SEQ ID NO: 141 2432 bp, SNP: 1313 T/C

CG50949-03 ORF Start: ATG at ORF Stop: TAG at 1870

DNA Sequence 112

GGACACTGACATGGACTGAAGGAGTAGAAAACATGCCTGAGAAGCCAGGGGCCAAGATGGATCTTCTCCT

CGACATCAGCTAAGCCTGGAGGACTCTCCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATGCATC

TCCAGCAAGAACACCTTCAGCTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGG GCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAG CCCAGGCATCTCCAGCTGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATC TCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGG TCATCATCCGCCAGGTCGGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAG TGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCC AGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTC CTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGT ACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAA GAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCC CATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGG GTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAG ATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGT GGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTG GGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCG GGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCACCATCAACAGCAATTACA CCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACAT CCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTT GGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACT TCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCT TCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG TACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAG TGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAG CAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGTAGGCAGAGGTCCCCTCAGCG

TCCCCATATTCGGGGGGTGTTCTGGACAGGGTCAAATGTGATGCCTGGGGTCAATCCCAGCTGTCTGTGT jTTCTTTCCCTGCTTTTCTTCCCTCAGAACAGAGCTCAGCGGGTTGAAAAAGGGTGGACCTACAGGCCAGG

CAGGCAGTTGCTGGGCAGATGTTCTCCCAGAAGTATTTTTTTGTGTAAGGTTGCAATGGACTTTGAAAAC

GTTTCAGTTTCTGCAGAGGATTTTGTGATAGTCTTTGTTATCAAGCATTTATGCATGGGAATCCGCTCTT

CATGGCCTTTCCCAGCTCTGTTTGTTTTAGTCTTTTTGATTTTCTTTTTGTTGTTGTTGTTGTCTTTTTT

TAAAAACACAAGTGACTCCATTTTAACTCTGACAACTTTCACAGCTGTCACCAGAATGCTCCCTGAGAAC TACCATTCTTTCCCTTTCCCACTTAAAATATTTCATCAGAACCTCACCACTATCATAAAAGAGTATAAAG

TAATAAAATAATAAAAAGCGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

NOV12t, 13374730 SNP for SEQ ID NO: 586 aa SNP: He to Thr at position 401

CG50949-03 142

Protein Sequence

MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGRAS PGRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSPARSA PATRATRESPGTSLPKFT REGQKQLPLIGCVLLLIALWSLIILFQFWQGHTGIRYKEQRESCPKHAVR CDGVVDCKXiKSDELGC/RFD DKSLLKIYSGSSHQ LPICSSNrøTDSYSEKTCQQLGFESAHRTTEVAHR DFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHI CGGTLIDAQWVLTAAHCFFVTREKVLEGWICVYAGTSNLHQLPEAASIAEITINSl^TDEEDDYDIAIMRL SKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYL TPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNB YIΛGVTSWGTGCGQRNKPGVYTKVTEVLP IYSKMEV RSLQQDTAPSRLGTSSGGDPGGAPRV

NOV12u, 13374731 SNP for SEQ ID NO: 143 2432 bp SNP: 1350 T/G

CG50949-03 ORF Start: ATG at 112 ORF Stop: TAG at 1870

DNA Sequence

GGACACTGACATGGACTGAAGGAGTAGAAAACATGCCTGAGAAGCCAGGGGCCAAGATGGATCTTCTCCT CGACATCAGCTAAGCCTGGAGGACTCTCCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATGCATC

TCCAGCAAGAACACCTTCAGCTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGG GCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAG CCCAGGCATCTCCAGCTGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATC TCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGG TCATCATCCGCCAGGTCGGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAG TGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCC AGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTC CTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGT ACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAA GAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCC CATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGG GTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAG ATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGT GGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTG GGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCG GGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACA CCGATGAGGAGGACGACTAGGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACAT

CCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTT

GGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACT

TCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCT

TCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG

TACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAG iTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAG

CAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGTAGGCAGAGGTCCCCTCAGCG iTCCCCATATTCGGGGGGTGTTCTGGACAGGGTCAAATGTGATGCCTGGGGTCAATCCCAGCTGTCTGTGT

TTCTTTCCCTGCTTTTCTTCCCTCAGAACAGAGCTCAGCGGGTTGAAAAAGGGTGGACCTACAGGCCAGG

CAGGCAGTTGCTGGGCAGATGTTCTCCCAGAAGTATTTTTTTGTGTAAGG

TTGCAATGGACTTTGAAAACGTTTCAGTTTCTGCAGAGGATTTTGTGATAGTCTTTGTTATCAAGCATTT

ATGCATGGGAATCCGCTCTTCATGGCCTTTCCCAGCTCTGTTTGTTTTAGTCTTTTTGATTTTCTTTTTG

TTGTTGTTGTTGTCTTTTTTTAAAAACACAAGTGACTCCATTTTAACTCTGACAACTTTCACAGCTGTCA

CCAGAATGCTCCCTGAGAACTACCATTCTTTCCCTTTCCCACTTAAAATATTTCATCAGAACCTCACCAC

TATCATAAAAGAGTATAAAGTAATAAAATAATAAAAAGCGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

AA

NOV12u, 13374731 SNP for SEQ ID NO: 586 aa • SNP: Tyr to STOP at position

CG50949-03 144 413

Protein Sequence

MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGRAS PGRAS AQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSPARSA PATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALWSLIILFQFWQGHTGIRYKEQRESCPKHAVR CDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHR DFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHI CGGTLIDAQ VLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEEDD*

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 12B.

Table 12B. Comparison of the NOV12 protein sequences.

N0V12a MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP

NOV12b

NOV12c

NOV12d

NOV12e

NOV12f

NOV12g N0V12h N0V121 TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP N0V12J TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP N0V12 MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP N0V121 N0V12m MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP N0V12n TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP N0V12o N0V12p NO I2q NOV12r

NOV12a AQASPAGTPPGRASPGRASPAQASPAQAS PARASPALASLSRSSSGRSSSARSAS NOV12b NOV12c NOV12d NOV12e NOV12f NOV12g NOV12h NOV12i AQASPAGTPPGRASPGRASPAQASPAQAS- -PARASPALASLSRSSSGRSSSARSAS NOV12J QASPAGTPPGRASP ALASLSRSSSGRSSSARSAS NOV12k AQASPAG PPGRASPGRASPAQASPAQAS- -PARASPALASLSRSSSGRSSSARSAS NOV121 NOV12m AQASPAGTPPGRASPGRASPAQASPAQASPAQASPARASPALASLSRSSSGRSSSARSAS NOV12n AQASPAGTPPGRASPGRASPAQAS PARASPALASLSRSSSGRSSSARSAS NOVI2o NOV12p NOV12q NOV12r

NOV12a VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFT REGQKQLPLIGC NOV12b NOV12c NOV12d NOV12e NOV12f NOVI2g NOV12h NOV12i VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFTWREGQKQLPLIGC NOV12J VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFT REGQKQLPLIGC NOV12k VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFT REGQKQLPLIGC NOV121 NOV12m VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESP NOV12n VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFTWREGQKQLPLIGC NOV12o MESPGTSL_PKFT REGQKQLPLIG_C NOV12p NOV12q NOVI2r

NOV12a VLLLIALWSLIILFQF QGHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDW

NOV12b

NOV12c

NOV12d -—GSTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDW

NOV12e -TGSHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDW

NOV12f -TGSHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFD

NOV12g -TGSHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFD NOV12h TGSHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDW NOV12i VLLLIALVVSLIILFQF QGHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFD NOV12J VLLLIALVVSLIILFQF QGHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFDW NOV12k VLLLIALWSLIILFQF QGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFD N0V121 TGSQF QGHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFD NOV12m VQF QGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12n VLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFD NOV12o VLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFD NOV12p FQFWQGHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFD NOV12q NOV12r -TGSQF QGHTGIRYKEQRESCPKHAVRCDGWDCKLKSDELGCVRFD

NOV12a DKSLLKIYSGSSHQ LPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12b NOV12c NOV12d DKSLLKIYSGSSHQWLPICSSN NDSYSEKTCQQLGFE NOV12e DKSLLKIYSGSSHQ LPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12f DKSLLKIYSGSSHQWLPICSSN NDSYSEKTCQQLGFE OV12g DKSLLKIYSGSSHQ LPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12h DKSLLKIYSGSSHQWLPICSSNRNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12i DKSLLKIYSGSSHQ LPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12J DKSLLKIYSGSSHQ LPICSSN NDSYSEKTCQQLGFE NOV12k DKSLLKIYSGSSHQ LPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV121 DKSLLKIYSGSSHQ LPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12m DKSLLKIYSGSSHQ LPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12n DKSLLKIYSGSSHQ LPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12o DKSLLKIYSGSSHQ LPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NO 12p DKSLLKIYSGSSHQ LPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12q NOV12r DKSLLKIYSGSSHQ LPICSSN NDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY

NOV12a NSTIQESLHRSECPSQRYISLQCSHCGLRA TGRIVGGALASDSKWP QVSLHFGTTHIC NOV12b SL IGSIVGGALASDSKWP QVSLHFGTTHIC NOV12c _SL IGSIVGGALASDSKWP QVSLHFGTTHIC NOV12d RSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK PWQVSLHFGTTHIC NOV12e NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK P QVSLHFGTTHIC NOV12f RSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK PWQVSLHFGTTHIC NOV12g NSTIQESLHRSECPFQRYISLQCSHCGLRAMTGRIVGGALVSDSK PWQVSLHFGTTHIC NOV12h NSTIQESLHRSECPSQRYISLQCSHCGLRA TGRIVGGALASDSK P QVSLHFGTTHIC NOV12i NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWP QVSLHFGTTHIC NOV12J RSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK PWQVSLHFGTTHIC NOV12k NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK PWQVSLHFGTTHIC NOV121 NSTIQESLHRSECPSQRYISLQCSHCGLRA TGRIVGGALASDSK P QVSLHFGTTHIC NOV12 NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK P QVSLHFGTTHIC NOV12n NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12o NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK P QVSLHFGTTHIC NOV12p NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK PWQVSLHFGTTHIC NOVl2q I_VGGALAS_DSK P _QV_SLHF_GTTHI_C NOV12r NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK PWQVSLHFGTTHIC

NOV12a GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12b GGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12c GGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOVl2d GGTLIDAQ VLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOVl2e GGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12f GGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12g GGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED N0V12h GGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED

N0V12i GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED

N0V12J GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED

N0V12k GGTLIDAQWVLTAAHCFFVTPJ5KVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED

NOV121 GGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED

NOV12m GGTLIDAQ VLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED

NOV12n GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED

NOV12o GGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED

NOV12p GGTLIDAQ VLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED

NOV12q GGTLIDAQWVLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED

NOV12r GGTLIDAQ VLTAAHCFFVTREKVLEG KVYAGTSNLHQLPEAASIAEIIINSNYTDEED

NOV12a DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ

NOV12b DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPSLREVQ

NOV12c DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPSLREVQ

N0V12d DYDIAL RLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ

N0V12e DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQ

N0V12f DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ

N0V12g DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQ

N0V12h DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQ

N0V12i DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ

N0V12J DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQ

N0V12k DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ

N0V121 DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ

N0V12 DYDIALMRLS PLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQ

N0V12n DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQ

N0V12O DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ

N0V12p DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQ

N0V12q DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPSLREVQ

N0V12r DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETC ITGFGKTRETDDKTSPFLREVQ

N0V12a VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12b VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12C VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12d VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTS

N0V12e VNLIDFKKCNDYLVYDSYLTPR MCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTSW

N0V12f VNLIDFKKCNDYLVYDSYLTPRMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTS

N0V12g VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12h VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12i VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12J VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12k VNLIDFKKCNDYLVYDSYLTPRM CAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW

N0V121 VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12m VNLIDFKKCNDYLVYDSYLTPR CAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12n VNLIDFKKCNDYLVYDSYLTPRM CAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTSW

N0V12O VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12p VNLIDF KCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12q VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12r VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNR YLAGVTS

N0V12a GTGCGQRNKPGVYTKVTEVLP IYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRV

N0V12b GTGCGQRNKPGVYTKVTEVLP IYSLE

N0V12c GTGCGQRNKPGVYTKVTEVLPWIYSLE

N0V12d GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLE-

N0V12e GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG

N0V12f GTGCGQRNKPGVYTKVTEVLP IYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG

N0V12g GTGCGQRNKPGVYTKVTEVLPWIYSKMEVKSLQQDTAPSRLGTSSGGDPGGAPRVLEG N0V12h GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG N0V12i GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAFSRLGTSSGGDPGGAPRVLEG NOV12J GTGCGQRNKPGVYTKVTEVLP IYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12k GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRV NOV121 GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12m GTGCGQRNKPGVYTKVTEVLPWIYSKMESEVRFRKS NOV12n GTGCGQRNKPGVYTKVTEVLPWIYSKMESEVRFRKSLEG NOV12o GTGCGQRNKPGVYTKVTEVLPWIYSKMESEVRFTKS N0V12p GTGCGQRNKPGVYTKVTEVLP IYSKMESEVRFTKS NOV12q GTGCGQRNKPGVYTKVTEVLP IYS NOV12r GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG

NOV12a (SEQ ID NO 104) NOV12b (SEQ ID NO 106) NOV12c (SEQ ID NO 108) NOV12d (SEQ ID NO 110) NOV12e (SEQ ID NO 112) NOV12f (SEQ ID NO 114) NOV12g (SEQ ID NO 116) NOV12h (SEQ ID NO 118) NOV12i (SEQ ID NO 120) NOV12J (SEQ ID NO 122) NOV12 (SEQ ID NO 124) NOV121 (SEQ ID NO 126) NOV12m (SEQ ID NO 128) NOV12n (SEQ ID NO 130) NOV12o (SEQ ID NO 132) NOV12p (SEQ ID NO 134) NOV12q (SEQ ID NO 136) NOV12r (SEQ ID NO 138)

Further analysis of the NOV12a protein yielded the following properties shown in Table 12C.

Table 12C. Protein Sequence Properties NOV12a

SignalP analysis: No Known Signal Sequence Predicted

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 4; pos.chg 1; neg.chg 2 H-region: length 8; peak value 0.00 PSG score: -4.40

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -6.21 possible cleavage site: between 24 and 25

>» Seems to have no N-terminal signal peptide

Tentative number of TMS(s) for the threshold 0.5: Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood =-15.71 Transmembrane 168 - 184 PERIPHERAL Likelihood = 2.86 (at 354) ALOM score: -15.71 (number of TMSs: 1)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 175 Charge difference: 0.5 C( 2.5) - N( 2.0) C > N: C-terminal side will be inside

>» membrane topology: type lb (cytoplasmic tail 168 to 586)

MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75) : 10.42 Hyd Moment (95) : 7.40 G content: 0 D/E content: 2 S/T content: 0 Score: -5.39

NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 10.2% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals :

XXRR-like motif in the N-terminus: ERDS none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2: none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: too long tail

Dileucine motif in the tail: found LL at 173 LL at 174 checking 63 PROSITE DNA binding motifs : none checking 71 PROSITE ribosomal protein motifs : none checking 33 PROSITE prokaryotic DNA binding motifs : none

NNCN: Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 94 . 1

COIL: Lupas ' s algorithm to detect coiled-coil regions total : 0 residues

Final Results (k = 9/23)

69.6 nuclear

13.0 mitochondrial

4.3 vacuolar

4.3 9- ■ plasma membrane

4.3 Q.. cytoplasmic

4.3 9"5, .• vesicles of secretory system

» prediction for CG50949-03 is nuc (k=23)

A search of the NOV12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12D.

In a BLAST search of public sequence databases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12E.

PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12F.

Example 13.

The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13 A.

Table 13A. NOV13 Sequence Analysis

NOV13a, CG51018-01 SEQ ID NO: 145 3447 bp

DNA Sequence fORF Start: ATG at 55 ORF Stop: TGA at 2932

GGTAGCCGACGCGCCGGCCGGCGCGTGACCTTGCCCCTCTTGCTCGCCTTGAAAATGGAAAAGATGCT

CGCAGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCCTCCTCCCTGCCGAGGCCAGGCAGCGGTCAC GTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGCAGACGGCCCTTCTGGAGAGTTCC TGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCTCGCAGTGTCAACACCCATGACTA TGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAATTCTTGGACATTGGTCCTGATGTCACCCGAG TGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAGTTCTCCCTCAAGACCTTCAAGAGGAAGTCC GAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTCCACGGGCACCATGACTGGGCTGGCCATCCA GTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGGCCCGGCCCCTGAGGGAGAATGTGCCACGGG TCATAATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCGAGGTGGCTGCTAAGGCACGGGAC ACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGTAGACTTCAACACCTTGAAGTCCATTGGGAG TGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATTTCAGCCAGATTGAGACGCTGACCTCCGTCT TCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACCCTGGAGCATAACTGTGCCCACTTCTGCATC AACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGGCTACATTCTCAACTCGGATCAGACGACTTG CAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACTGTGAGCAGCTCTGTGTGAATGTGCCGGGCT CCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGGATGGGAAGAGGTGTGTGGCTGTGGAC TACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTGTGTAAATGCTGATGGCTCCTACCTTTGCCA GTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAACGTGCACAAAGATAGACTACTGTGCCTCAT CTAATCATGGATGTCAGTACGAGTGTGTTAACACAGATGATTCCTATTCCTGCCACTGCCTGAAAGGC TTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGATCAACTACTGTGCACTGAACAAACCGGGCTG TGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACTGCCGCTGCCACCGTGGCTACACTCTGGACC CCAATGGCAAACCCTGCAGCCGAGTGGACCACTGTGCACAGCAGGACCATGGCTGTGAGCAGCTGTGT CTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTCCTCATCAACGAGGACCTCAAGAC CTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGAATACTCCTGTGTCAACATGGACA GATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTCCGCAGCGATGGGAAGACGTGTGCAAAATTG GACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTCGTGTGTAAGCAGTGAAGATTCGTTTGTGTG CCAGTGCTTTGAAGGTTATATACTCCGTGAAG^TGGAAAAACCTGCAGAAGGAAAGATGTCTGCCAAG CTATAGACCATGGCTGTGAACACATTTGTGTGAACAGTGACGACTCATACACGTGCGAGTGCTTGGAG GGATTCCGGCTCACTGAGGATGGGAAACGCTGCCGAATTTCCTCAGGGAAGGATGTCTGCAAATCAAC CCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACATCTGCAAATGeTCAGAGGGAT TTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGCCCAATTGACCTGGTCTTTGTG ATCGATGGATCCAAGAGTCTTGGAGAAGAGAATTTTGAGGTCGTGAAGCAGTTTGTCACTGGAATTAT AGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCCAGTATTCCACACAGGTCCACA CAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAAGCCGTGGCCCACATGAAATAC ATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGAGAGAAGTTTTACCCAAGGAGA AGGGGCCAGGCCCTTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGTTCACCGACGGACGGGCTCAGG ATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATGGTATCACTATGTATGCTGTTGGGGTAGGA AAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAACAAGCATCTCTTCTATGCCGA AGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAGAAAGGCATCTGTGAAGCTCTAGAAGACT CCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTCCAACAGCCAACAGAATCTGAG CCAGTCACCATAAATATCCAAGACCTACTTTCCTGTTCTAATTTTGCAGTGCAACACAGATATCTGTT TGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAACAAAACCTTCAGGAAGCCCTT TGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTCCAGAACCTTGCAAACGAAGAA GTAAGAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGAAGCCCTGGAAAATCGCCTGAG ATACAGATGAAGATTAGAAATCGCGACACATTTGTAGTCATTGTATCACGGATTACAATGAACGCAGT GCAGAGCCCCAAAGCTCAGGCTATTGTTAAATCAATAATGTTGTGAAGTAAAACAATCAGTACTGAGA AACCTGGTTTGCCACAGAACAAAGACAAGAAGTATACACTAACTTGTATAAATTTATCTAGGAAAAAA ATCCTTCAGAATTCTAAGATGAATTTACCAGGTGAGAATGAATAAGCTATGCAAGGTATTTTGTAATA TACTGTGGACACAACTTGCTTCTGCCTCATCCTGCCTTAGTGTGCAATCTCATTTGACTATACGATAA NOV13c, 274051251 SEQ ID NO: 149 2893 bp

DNA Sequence JORF Start: at 2 ORF Stop: end of sequence

CACCAGATCTCCCACCATGGAAAAGATGCTCGCAGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCC TCCTCCCTGCCGAGGCCAGGGAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACC CACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGA CAGCTCTCGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAAT TCTTGGACATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAG TTCTCCCTCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTC CACGGGCACCATGACTGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGG CCCGGCCCCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCC GTGGCCGAGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGT AGACTTCAACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATT TCAGCCAGATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACC CTGGAGCATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGG CTACATTCTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACT GTGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCT GAGGATGGGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTG TGTAAATGCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAA CGTGCACAAAGATAGACTACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGAT GATTCCTATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGAT CAACTACTGTGCACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACT GCCGCTGCCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCA CAGCAGGACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGA AGGCTTCCTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATG GTTGTGAATACTCCTGTGTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTC CGCAGCGATGGGAAGACGTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTC GTGTGTAAGCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAA AAACCTGCAGAAGGAAAGATGTCTGCCAAGCTATAGACCATGGCTGTGAACACATTTGTGTGAACAGT GACGACTCATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAG GAAGGATGTCTGCAAATCAACCCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACA TCTGCAAATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGC CCAATTGACCTGGTCTTTGTGATCGATGGATCCAAGAGTCTTGGAGAAGAGAATTTTGAGGTCGTGAA GCAGTTTGTCACTGGGATTATAGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCC AGTATTCCACACAGGTCCACACAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAA GCCGTGGCCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGA GAGAAGTTTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGT TCACCGACGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATGGTATCACT ATGTATGCTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAA CAAGCATCTCTTCTATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAGAAAGGCA TCTGTGAAGCTCTAGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTC CAACAGCCAACAGAATCTGAGCCAGTCACCATAAATATCCAAGACCTACTTTCCTGTTCTAATTTTGC AGTGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAA CAAAACCTTCAGGAAGCCCTTTGGAAG7^AAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTC CAGAACCTTGCAAACGAAGAAGTAAGAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGA AGCCCTGGAAAATCGCCTGAGATACAGAGTCGACGGC

NOV13c, 274051251 SEQ ID NO: 150 ! 964 aa MW at 107650.5kD Protein Sequence

TRSPTMEK LAGCFLIILLGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENKRADLVFIID SSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSL TF RKSEVERAVKRMRHLS TG MTGLAIQYALNIAFSEAEGARPLRENVPRVI IVTDGRPQDSVAEVAA ARDTGILIFAIGVGQV DFNTL SIGSEPHEDTTVFLVANFSQIETLTSVFQKKLCTAHMCSTLEH CAHFCINIPGSYVCRCKQG

YIIJNSDQTTCRIQDLCAMEDHNCEQLCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASE HGCEHEC V ADGSYLCQCHEGFALNPDEKTCTKIDYCASS HGCQHECV TDDSYSCHCLKGFTLNPDKKTCRRI NYCALNKPGCEHECVNMEESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSE GFLI EDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHS CVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAEDGKRCRR KDVCKSTHHGCEHICλraNGNSYICKCSEGFVLAEDGRRCKKCTEGPlDLVFVIDGSKSLGEENFEVVK QFV GIIDSLTISPKAARVGLLQYSTQVHTEFTLR FNSAKDMK-XΑVAHMKYMGKGS TGIiALKH FE RSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSE ASKAKANGI MYAVGVGKAIEEELQEIASEP N KHLFYAEDFST DEISEKLKKGICEALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFA VQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME ALE RLRYRVDG

NOV13d, 274051253 SEQ ID NO: 151 2893 bp DNA Sequence ORF Start: at 2 jORF Stop: end ofsequence

CACCAGATCTCCCACCATGGAAAAGATGCTCGCAGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCC TCCTCCCTGCCGAGGCCAGGGAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACC CACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGA CAGCTCTCGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAAT TCTTGGACATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAG TTCTCCCTCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTC CACGGGCACCATGACTGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGG CCCGGCCCCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCC GTGGCCGAGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGT AGACTTCAACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATT TCAGCCAGATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACC CTGGAGCATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGG CTACATTCTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACT GTGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCT GAGGATGGGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTG TGTAAATGCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAA CGTGCACAAAGATAGACTACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGAT GATTCCTATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGAT CAACTACTGTGCACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACT GCCGCTGCCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCA CAGCAGGACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGA AGGCΓTCCTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATG GTTGTGAATACTCCTGTGTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTC CGCAGCGATGGGAAGACGTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTC GTGTGTAAGCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAA AAACCTGCAGAAGGAAAGATGTCTGCCAAGCTATAGACCATGGCTGTGAACACATTTGTGTGAACAGT GACGACTCATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAG GAAGGATGTCTGCAAATCAACCCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACA TCTGCAAATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGC CCAATTGACCTGGTCTTTGTGATCGATGGATCCAAGAGTCTTGGAGAAGAGAATTTTGAGGTCGTGAA GCAGTTTGTCACTGGGATTATAGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCC AGTATTCCACACAGGTCCACACAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAA GCCGTGGCCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGA GAGAAGTTTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGT TCACCGACGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATGGTATCACT ATGTATGCTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAA CAAGCATCTCTTCTATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAGAAAGGCA TCTGTGAAGCTCTAGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTC CAACAGCCAACAGAATCTGAGCCAGTCACCATAAATATCCAAGACCTACTTTCCTGTTCTAATTTTGC AGTGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAA CAAAACCTTCAGGAAGCCCTTTGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTC CAGAACCTTGCAAACGAAGAAGTAAGAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGA AGCCCTGGAAAATCGCCTGAGATACAGAGTCGACGGC

NOV13d, 274051253 SEQ ID NO: 152 964 aa MW at l07650.5kD Protein Sequence

TRSPTME MLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENKRADLVFIID SSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSΪVKNEFSLKTFKRKSEVERAVKR RHLS TGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAA ARDTGILIFAIGVGQV DFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKKXiCTAHMCSTLEHNCAHFCINIPGSYVCRCKQG YILNSDQTTCRIQDLCAMEDH CEQLCV VPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHEC VNADGSYLCQCHEGFALNPDE TCTKIDYCASSlrøGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRI NYCALN PGCEHECVNMEESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSE GFLINEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHS CVSSEDSFVCQCFEGYILREDG TCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAEDGKRCRR KDVCKSTHJEΪGCEHICVNNGNSYICKCSEGFVLAEDGRRCK CTEGPIDLVFVIDGSKSLGEENFEVV QFVTGIIDSLTISP ΛARVGLLQYSTQVHTEFTLRNFNSAKDM KAVAHMKYMGKGSMTGLALKH FE RSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSE AS AKANGITMYAVGVGKAIEEELQEIASEP N KHLFYAEDFSTMDEISEKLKKGICEALEDSDGRQDSPAGΞLP TVQQPTESEPVTINIQDLLSCSNFA VQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME ALENRLRYRVDG

NOV13e, 306562753 SEQ ID NO: 153 2836 bp DNA Sequence

ORF Start: at 2 ORF Stop: end of sequence

CACCAGATCTCCCACCATGGAAAAGATGCTCGCAGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCC TCCTCCCTGCCGAGGCCAGGGAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACC CACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGA CAGCTCTCGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAAT TCTTGGACATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAG TTCTCCCTCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTC CACGGGCACCATGACCGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGG CCCGGCCCCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCC GTGGCCGAGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGT AGACTTCAACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATT TCAGCCAGATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACC CTGGAGCATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGG CTACATTCTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACT GTGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCT GAGGATGGGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTG TGTAAATGCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAA CGTGCACAAAGATAGACTACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGAT GATTCCTATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGAT CAACTACTGTGCACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACT GCCGCTGCCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCA CAGCAGGACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGA AGGCTTCCTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATG GTTGTGAATACTCCTGTGTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTC CGCAGCGATGGGAAGACGTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTC GTGTGTAAGCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAA AAACCTGCAGAAGGAAAGATGTCTGCCAAGCTATAGACCATGGCTGTGAACACATTTGTGTGAACAGT GACGACTCATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAG GAAGGATGTCTGCAAATCAACCCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACA TCTGCAAATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGC CCAATTGACCTGGTCTTTGTGATCGATGGATCCAAGAGTCTTGGAGAAGAGAATTTTGAGGTCGTGAA GCAGTTTGTCACTGGAATTATAGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCC AGTATTCCACACAGGTCCACACAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAA GCCGTGGCCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGA GAGAAGTTTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGT TCACCGACGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATGGTATCACT ATGTATGCTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAA CAAGCATCTCTTCTATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAGAAAGGCA TCTGTGAAGCTCTAGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTC CAACAGCCAACAGTGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCT TTCCCATTCAACAAAACCTTCAGGAAGCCCTTTGGAAGAAAAACACGATCAATGCAAATGTGAAAACC TTATAATGTTCCAGAACCTTGCAAACGAAGAAGTAAGAAAATTAACACAGCGCTTAGAAGAAATGACA CAGAGAATGGAAGCCCTGGAAAATCGCCTGAGATACAGAGTCGACGGC NOV13e, 306562753 SEQ ID NO: 154 945 aa MW t l05588.3kD Protein Sequence RSPTMΞKMLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCE2M RADLVFIID SSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNΞFSL TF RKSEVERAVKR RHLS iTGTMTGIiAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAAKARDTGILIFAIGVGQV DFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKKLCTAHMCSTLEHNCAHFCINIPGSYVCRCKQG lLNSDQTTCRIQDLCA EDH CEQLCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHEC 'VNADGSYLCQCHEGFAIjNPDE TCTKIDYCASS HGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRI NYCALN PGCEHECVNMEESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSE GFLINEDLKTCSRVDYCLLSDHGCEYSCVN DRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHS CVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAEDGKRCRR KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCTEGPIDLVFVIDGSKSLGEENFEVVK QFVTGIIDSLTISPKAARVGLLQYSTQVHTEFTLRNFNSADMKKAVAHMKYMGKGSMTGIαAL HMFE RSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSEWASKAKANGIT YAVGVGKAIEEELQEIASEP N KHLFYAEDFSTMDEISEKLKKGICEALEDSDGRQDSPAGELPKTVQQPTVQHRYLFEEDNLLRSTQKL SHSTKPSGSPLEEKHDQCKCENLI FQNLANEEVRKLTQRLEEMTQRMEALE RLRYRVDG

NOV13f, CG51018-02 SEQ ID NO: 155 J2742 bp

DNA Sequence JQRF Start: at 1 JORF Stop: end of sequence

AGGCAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGCAGACGGCCCT TCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCTCGCAGTGTCA ACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAATTCTTGGACATTGGTCCT GATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAGTTCTCCCTCAAGACCTT CAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTCCACGGGCACCATGACTG GGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGGCCCGGCCCCTGAGGGAG AATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCGAGGTGGCTGC TAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGTAGACTTCAACACCTTGA AGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATTTCAGCCAGATTGAGACG CTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACCCTGGAGCATAACTGTGC CCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGGCTACATTCTCAACTCTG ATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACTGTGAGCAGCTCTGTGTG AATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGGATGGGAAGAGGTG TGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTGTGTAAATGCTGATGGCT CCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATAAGAAAACGTGCACAAAGATAGAC TACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGATGATTCCTATTCCTGCCA CTGTCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAGCCTGCAGAAGGATCAACTACTGTGCACTGA ACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACTGCCGCTGCCACCGTGGC TACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCACAGCAGGACCATGGCTG TGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTCCTCATCAACG AGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGAATACTCCTGT GTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTCCGCAGCGATGGGAAGAC GTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTCGTGTGTAAGCAGTGAAG ATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAAAAACCTGCAGAAGGAAA GATGTCTGCCAAGCTATAGACCATGGCTGTGAACACATTTGTGTGAACAGTGACGACTCATACACGTG CGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAGGAAGGATGTCTGCAAAT CAACCCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACATCTGCAAATGCTCAGAG GGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGCCCAATTGACCTGGTCTT TGTGATCGATGGATCCAAGAGTCTTGGAGAAGAGAATTTTGAGGTCGTGAAGCAGTTTGTCACTGGAA TTATAGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCCAGTATTCCACACAGGTC CACACAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAAGCCGTGGCCCACATGAA ATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATCTTTGAGAGAAGTTTTACCCAAG GAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGTTCACCGACGGACGGGCT CAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATTGTATCACTATGTATGCTGTTGGGGT AGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAACAAGCATCTCTTCTATG CCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAGAAAGGCATCTGTGAAGCTCTAGAA GACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTCCAACAGCCAACAGTGCA ACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAACAAAAC CTTCAGGAAGCCC TTGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTCCAGAAC CTTGCAAACGAAGAAGTAAGAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGAAGCCCT GGAAAATCGCCTGAGATACAGA

NOV13f, CG51018-02 SEQ ID NO: 156 914 aa MW at l02314.4kD Protein Sequence

RQRSRGRSISRGRHARTHPQTALLESSCENKRADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGP DVTRVGLLQYGSTVKNEFSLKTFKR SEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRE NVPRVIMIVTDGRPQDSVAEVAA ARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIET LTSVFQKKLCTAHMCSTLEH CAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCA EDHNCEQLCV NVPGSFVCQCYSGYALAEDGKRCVAVDYCASE HGCEHECVNADGSYLCQCHEGFALNPDKKTCTKID YCASS HGCQHECVNTDDSYSCHCLKGFTLNPD ACRRI YCALWKPGCEHECVN EESYYCRCHRG YTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKTCSRVDYCLLSDHGCEYSC VNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCVSSEDSFVCQCFEGYILREDGKTCRRK DVCQAIDHGCEHIC^SDDSYTCECLEGFRLAEDGKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSE GFVLAΞDGRRCKKCTΞGPIDLVFVIDGSKSLGEENFEW QFVTGIIDSLTISPKAARVGLLQYSTQV HTEFTLRNFNSAKDMKKAVAHMKYMGKGSMTGLALKHIFERSFTQGEGARPLSTRVPRAAIVFTDGRA QDDVSE ASKAKANCITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALE DSDGRQDSPAGELPKTVQQPTVQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQN LANEEVRKLTQRLEEMTQRMEALENRLRYR

|NOV13g, CG51018-03 jSEQ ID NO: 157 ;2756 bp

DNA Sequence JORF Start: ATG at o [ORF Stop: TGA at 2718

TGACCTTGCCCCTCTTGCTCGCCTTGAAAATGGAAAAGATGCTCGCAGGCTGCTTTCTGCTGATCCTC

GGACAGATCGTCCTCCTCCCTGCCGAGGCCAGGGAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAG ACACGCTCGGACCCACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAACATGCGGGCAGACCTGG TTTTCATCATTGACAGCTCTCGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTG GACATCTTGCAATTCTTGGACATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCAC TGTCAAGAATGAGTTCTCCCTCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGA TGCGGCATCTGTCCACGGGCACCATGACCGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCA GAAGCAGAGGGGGCCCGGCCCCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAG ACCTCAGGACTCCGTGGCCGAGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTG GTGTGGGCCAGGTAGACTTCAACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTC CTTGTGGCCAATTTCAGCCAGATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCA CATGTGCAGCACCCTGGAGCATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCA GGTGCAAACAAGGCTACATTCTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATG GAGGACCACAACTGTGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGG CTACGCCCTGGCTGAGGATGGGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCATCTAATCACGGAT GTCAGCACGAGTGTGTTAACACAGATGATTCCTATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAAT CCAGATAAGAAAACCTGCAGAAGGATCAACTACTGTGCACTGAACAAACCGGGCTGTGAGCATGAGTG CGTCAACATGGAGGAGAGCTACTACTGCCGCTGCCACCGTGGCTACACTCTGGACCCCAATGGCAAAA CCTGCAGCCGAGTGGACCACTGTGCACAGCAGGACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAG GATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTCCTCATCAACGAGGACCTCAAGACCTGCTCCCGGGT GGATTACTGCCTGCTGAGTGACCATGGTTGTGAATACTCCTGTGTCAACATGGACAGATCCTTTGCCT GTCAGTGTCCTGAGGGACACGTGCTCCGCAGCGATGGGAAGACGTGTGCAAAATTGGACTCTTGTGCT CTGGGGGACCACGGTTGTGAACATTCGTGTGTAAGCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGA AGGTTATATACTCCGTGAAGATGGAAAAACCTGCAGAAGGAAAGATGTCTGCCAAGCTATAGACCATG GCTGTGAACACATTTGTGTGAACAGTGATGACTCATACACGTGCGAGTGCTTGGAGGGATTCCGGCTC GCTGAGGATGGGAAACGCTGCCGAAGGAAGGATGTCTGCAAATCAACCCACCATGGCTGCGAACACAT TTGTGTTAATAATGGGAATTCCTACATCTGCAAATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAA GACGGTGCAAGAAATGCACTGAAGGCCCAATTGACCTGGTCTTTGTGATCGATGGATCCAAGAGTCTT GGAGAAGAGAATTTTGAGGTCGTGAAGCAGTTTGTCACTGGAATTATAGATTCCTTGACAATTTCCCC CAAAGCCGCTCGAGTGGGGCTGCTCCAGTATTCCACACAGGTCCACACAGAGTTCACTCTGAGAAACT TCAACTCAGCCAAAGACATGAAAAAAGCCGTGGCCCACATGAAATACATGGGAAAGGGCTCTATGACT GGGCTGGCCCTGAAACACATGTTTGAGAGAAGTTTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCAC AAGGGTGCCCAGAGCAGCCATTGTGTTCACCGACGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCA GTAAAGCCAAGGCCAATGGTATCACTATGTATGCTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTA CAAGAGATTGCCTCTGAGCCCACAAACAAGCATCTCTTCTATGCCGAAGACTTCAGCACAATGGATGA GATAAGTGAAAAACTCAAGAAAGGCATCTGTGAAGCTCTAGAAGACTCCGATGGAAGACAGGACTCTC CAGCAGGGGAACTGCCAAAAACGGTCCAACAGCCAACAGTGCAACACAGATATCTGTTTGAAGAAGAC iAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAACAAAACCTTCAGGAAGCCCTTTGGAAGAAAA ACACGATCAATGCAAATGTGAAAACCTTATAATGTTCCAGAACCTTGCAAACGAAGAAGTAAGAAAAT TAACACAGCGCTTAGAAGAAATGACACAGAGAATGGAAGCCCTGGAAAATCGCCTGAGATACAGATGA AGATTAGAAATCGCGACACATTTGTAAAGGGCGAAT

NOV13g, CG51018-03 SEQ ID NO: 158 896 aa MW at 100259.6kD Protein Sequence

ME LAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCElSIMRADLVFIIDSSRSV ΪTTHDYAKVIvΕFIVDILQFLDIGPDVTRVGLLQYGSTV NEFSL TFKRKSEVERAVKRMRHLSTGTMT GLAIQYALNIAFSEAEGARPLRE VPRVIMIVTDGRPQDSVAEVAA ARDTGILIFAIGVGQVDFNTL KSIGSEPHEDHVFLVANFSQIETLTSVFQ KLCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNS DQTTCRIQDLCA EDHNCEQLCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASSNHGCQHECVNTDD SYSCHCIiKGFTLNPD KTCRRINYCALNKPGCEHECVNMEESYYCRCHRGYTLDPNGKTCSRVDHCAQ QDHGCEQLCLNTEDSFVCQCSEGFLINEDL TCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLR SDG TCAKLDSCALGDHGCEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICV SD DSYTCECLEGFRLAEDGKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCTEGP IDLVFVIDGSKSLGEENFEWKQFVTGIIDSLTISPKAARVGLLQYSTQVHTEFTLRNFNSAKDM KA VAHMKYMGKGSMTGLAL HMFERSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSΞ AS AKANGITM YAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKL GICEALEDSDGRQDSPAGELPKTVQ QPTVQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQC CENLIMFQNIiANEEVRKLTQRLEEMTQ R EALENRLRYR

NOV13h, 13374217 SNP for SEQ ID NO: 3447 bp SNP: 462 T/C

CG51018-01 159

DNA Sequence ORF Start: ORF Stop: end of sequence ATG at 55

GGTAGCCGACGCGCCGGCCGGCGCGTGACCTTGCCCCTCTTGCTCGCCTTGAAAATGGAAAAGATGCTCGC

AGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCCTCCTCCCTGCCGAGGCCAGGCAGCGGTCACGTGGGA GGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAAC AAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCTCGCAGTGTCAACACCCATGACTATGCAAAGGTCAA GGAGTTCATCGTGGACATCTTGCAATTCTTGGACATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAAT ATGGCAGCACTGTCAAGAATGAGTTCTCCCTCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTC AAGAGGATGCGGCATCTGTCCACGGGCACCATGACCGGGCTGGCCATCCAGTATGCCCTGAACATCGCATT CTCAGAAGCAGAGGGGGCCCGGCCCCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGA GACCTCAGGACTCCGTGGCCGAGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGT GTGGGCCAGGTAGACTTCAACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGT GGCCAATTTCAGCCAGATTGAGACGCTGACCTCCGTCTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCA GCACCCTGGAGCATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAA GGCTACATTCTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACTG TGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGG ATGGGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTGTGTAAAT GCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGA^AAAACGTGCACAA GATAGACTACTGTGCCTCATCTAATCATGGATGTCAGTACGAGTGTGTTAACACAGATGATTCCTATTCCT GCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGATCAACTACTGTGCACTG AACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACTGCCGCTGCCACCGTGGCTA CACTCTGGACCCCAATGGCAAACCCTGCAGCCGAGTGGACCACTGTGCACAGCAGGACCATGGCTGTGAGC AGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTCCTCATCAACGAGGACCTC AAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGAATACTCCTGTGTCAACATGGA CAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTCCGCAGCGATGGGAAGACGTGTGCAAAATTGG ACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTCGTGTGTAAGCAGTGAAGATTCGTTTGTGTGCCAG TGCTTTGAAGGTTATATACTCCGTGAAGATGGAAAAACCTGCAGAAGGAAAGATGTCTGCCAAGCTATAGA CCATGGCTGTGAACACATTTGTGTGAACAGTGACGACTCATACACGTGCGAGTGCTTGGAGGGATTCCGGC TCACTGAGGATGGGAAACGCTGCCGAATTTCCTCAGGGAAGGATGTCTGCAAATCAACCCACCATGGCTGC GAACACATTTGTGTTAATAATGGGAATTCCTACATCTGCAAATGCTCAGAGGGATTTGTTCTAGCTGAGGA CGGAAGACGGTGCAAGAAATGCACTGAAGGCCCAATTGACCTGGTCTTTGTGATCGATGGATCCAAGAGTC TTGGAGAAGAGAATTTTGAGGTCGTGAAGCAGTTTGTCACTGGAATTATAGATTCCTTGACAATTTCCCCC AAAGCCGCTCGAGTGGGGCTGCTCCAGTATTCCACACAGGTCCACACAGAGTTCACTCTGAGAAACTTCAA CTCAGCCAAAGACATGAAAAAAGCCGTGGCCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGG CCCTGAAACACATGTTTGAGAGAAGTTTTACCCAAGGAGAAGGGGCCAGGCCCTTTTCCACAAGGGTGCCC AGAGCAGCCATTGTGTTCACCGACGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGC CAATGGTATCACTATGTATGCTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTG AGCCCACAAACAAGCATCTCTTCTATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAG AAAGGCATCTGTGAAGCTCTAGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAAC GGTCCAACAGCCAACAGAATCTGAGCCAGTCACCATAAATATCCAAGACCTACTTTCCTGTTCTAATTTTG CAGTGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAACA AAACCTTCAGGAAGCCCTTTGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTCCAGAA CCTTGCAAACGAAGAAGTAAGAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGAAGCCCTGG AAAATCGCCTGAGATACAGATGAAGATTAGAAATCGCGACACATTTGTAGTCATTGTATCACGGATTACAA

TGAACGCAGTGCAGAGCCCCAAAGCTCAGGCTATTGTTAAATCAATAATGTTGTGAAGTAAAACAATCAGT

ACTGAGAAACCTGGTTTGCCACAGAACAAAGACAAGAAGTATACACTAACTTGTATAAATTTATCTAGGAA

AAAAATCCTTCAGAATTCTAAGATGAATTTACCAGGTGAGAATGAATAAGCTATGCAAGGTATTTTGTAAT

ATACTGTGGACACAACTTGCTTCTGCCTCATCCTGCCTTAGTGTGCAATCTCATTTGACTATACGATAAAG

TTTGCACAGTCTTACTTCTGTAGAACACTGGCCATAGGAAATGCTGTTTTTTTGTACTGGACTTTACCTTG

ATATATGTATATGGATGTATGCATAAAATCATAGGACATATGTACTTGTGGAACAAGTTGGATTTTTTATA

CAATATTAAAATTCACCACTTCAGAGAAAAGTAAAAAAA

NOV13h, 13374217 SNP SEQ ID NO: 959 aa SNP: no change in the protein for 1160 sequence

CG51018-01

Protein Sequence

MEKMLAGCFLLILGQIVLLPAEARQRSRGRSISRGRHARTHPQTALLESSCENKRADLVFIIDSSRSVNTH DYAKTEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFKRKSEVERAVRRHLSTGTMTGLAIQY ALNIAFSEAEGARPLRENVPRVIMI TDGRPQDSVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHE DHVFLVANFSQIETLTSVFQIOLCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCA MEDHNCEQLCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD EKTCTKIDYCASSNHGCQYECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCAL KPGCEHECVrøffiESYYC RCHRGYTLDPNGKPCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKTCSRVDYCLLSDHGCEY SCVNMDRSFACQCPEGHVLRSDGTCAKLDSCALGDHGCEHSCVSSEDSFVCQCFEGYILREDGKTCRR D VCQAIDHGCEHICVNSDDSYTCΞCLEGFRLTEDGKRCRISSGKDVCKSTHHGCEHICVNNGNSYICKCSEG FVLAEDGRRCKKCTEGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSIiTISPKAARVGLLQYSTQVHTEF TLRNFNSAKD KAVAHMKYMGKGSMTGIiALKHMFERSFTQGEGARPFSTRVPRAAIVFTDGRAQDDVSEW ASKAKANGITMYAVGVG AIEΞELQEIASEPTNHLFYAEDFSTMDEISE LKKGICEALEDSDGRQDSPA GELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFEΞDNLLRSTQKLSHST PSGSPLEEKHDQCKCEN LIMFQNLANEEVRKLTQRLEEMTQRMEALENRLRYR

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 13B.

Table 13B. Comparison of the NOV13 protein sequences.

NOV13a MEKMLAGCFLLILGQIVLLPAEARQRSRGRSISRGRHARTHPQTALLESSCENKR

NOV13b

NOV13c TRSPTMEKMLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENKR

NOV13d TRSPTMEKMLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENKR

NOV13e TRSPTMEK LAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENKR

NOV13f RQRSRGRSISRGRHARTHPQTALLESSCENKR

NOV13g EKMLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENMR

NOV13a ADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFK

NOV13b

N0V13c ADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVϊCEFSLKTFK

N0V13d ADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFK

N0V13e ADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKEFSLKTFK NOV13f ADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFK N0V13g ADLVFIIDSSRSVNTHDYA VKEFIVDILQFLDIGPDVTRVGLLQYGSTVK EFSLKTFK

NOV13a RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVI IVTDGRPQD N0V13b NOV13c RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVI IVTDGRPQD NOV13d RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQD N0V13e RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQD N0V13f RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQD N0V13g RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQD

NOV13a SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK NOV13b NOV13c SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQK NOV13d SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK N0V13e SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK N0V13f SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVF KK N0V13g SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK

N0V13a LCTAH CSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV N0V13b NOV13c LCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOV13d LCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOVI3e LCTAH CSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOVI3f LCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOV13g LCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV

NOV13a NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD

NOV13b

NOV13c NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD

NOV13d NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLC CHEGFALNPD

NOV13e NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD

NOV13f NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD

NOV13g NVPGSFVCQCYSGYALAEDGKRCVAVDYCASS

NOV13a EKTCTKIDYCASSNHGCQYECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH

NOV13b

NOV13c EKTCTK1DYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH

NOV13d EKTCT IDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH

NOV13e EKTCTKIDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH

NOV13f KKTCTKIDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKACRRINYCALNKPGCEH

NOV13g NHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH

NOV13a ECVNMEESYYCRCHRGYTLDPNGKP-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL

NOV13b ALEGFSESHLA-LH—LAVNP-GKNFCHFGVH—TRFVSLATACAPAGD—TCQVPAWL

NOV13C ECVNMEESYYCRCHRGYTLDPNGKT-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL

NOV13d ECVNMEESYYCRCHRGYTLDPNGKT-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL

NOV13e ECVNMEESYYCRCHRGYTLDPNGKT-CSRVDHCAQQDHGCEQLCLNTEDSFVC CSEGFL

NOV13f ECVNMEESYYCRCHRGYTLDPNGKT-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL

NOV13g ECVNMEESYYCRCHRGYTLDPNG T-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL

NOV13a INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH

NOV13b LTDKRP—PAVSLAGVSAP TKVPSTHH P GKVTVIDQWIAFLEVDEIDLH

NOV13C INEDL TCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH

NOV13d INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH

NOV13e INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH

NOV13f INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH N0V13g INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDG TCAKLDSCALGDH

N0V13a G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL

NOVI3b LPEEGGCLVI CLPGLA KACDPAGLIEAKGLS-MHGEASRVD—VSGQG

N0V13c G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL

NOV13d G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL

N0V13e G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL

N0V13f G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL

N0V13g G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL

N0V13a EGFRLTEDGKRCRISSGKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT

N0V13b QGLGQPHEG DVIVVLLIGVIAVDDDLGNG GCLRQLVQVA-GAR V

N0V13C EGFRLAEDGKRCRR KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT

N0V13d EGFRLAEDGKRCRR KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT

N0V13e EGFRLAEDGKRCRR KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT

N0V13f EGFRLAEDGKRCRR KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT

N0V13g EGFRLAEDGKRCRR KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT

N0V13a EGPIDLVFVIDGSKSLGEENFEWKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL

N0V13b HLPA—LQDLLP GHE—EAVG GSEHPLGVNERASTDVGGAEV—QTHLPRPL

N0V13c EGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL

N0V13d EGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL

N0V13e EGPIDLVFVIDGSKSLGEENFEWKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL

N0V13f EGPIDLVFVIDGSKSLGEENFEWKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL

N0V13g EGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL

N0V13a RNFNSAKDMKKAVAHMKY GKGSMTGLALKH FERSFTQGEGARPFSTRVPRAAIVFTDG

N0V13b AIRGQRP SHDP PG HGPQSAVGTLEGDIPLG-RAFRPVEAFLDG

N0V13c RNFNSAKDMKKAVAH KYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDG

N0V13d RNFNSAKDMKKAVAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDG

N0V13e RNFNSAKD KKAVAHMKY GKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDG

N0V13f RNFNSAKDMKKAVAHMKYMGKGSMTGLALKHIFERSFTQGEGARPLSTRVPRAAIVFTDG

N0V13g RNFNSAKDMKKAVAH KYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDG

N0V13a —RAQDDVSE ASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS

N0V13b GVVSQD

N0V13c —RAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS

N0V13d —RAQDDVSE ASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS

N0V13e —RAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS

N0V13f --RAQDDVSEWASKAKANCITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFST DEIS

N0V13g —RAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS

N0V13a EKLKKGICEALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFE

N0V13b

N0V13c EKLKKGICEALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFE

N0V13d EKLKKGICEALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFE

N0V13e E LKKGICEALEDSDGRQDSPAGELPKTVQQPT VQHRYLFE

N0V13f EKLKKGICEALEDSDGRQDSPAGELPKTVQQPT VQHRYLFE

N0V13g EKLKKGICEALEDSDGRQDSPAGELPKTVQQPT VQHRYLFE

N0V13a EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME

N0V13b

N0V13c EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME

N0V13d EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME

N0V13e EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLI FQNLANEEVRKLTQRLEEMTQRE

N0V13f EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME

N0V13g EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME NOV13a ALENRLRYR

NOV13b

NOV13c ALENRLRYRVDG

NOV13d ALENRLRYRVDG

NOV13e ALENRLRYRVDG

NOVl3f ALENRLRYR

NOVl3g ALENRLRYR

NOV13a (SEQ ID NO 146)

NOV13b (SEQ ID NO 148)

NOVl3c (SEQ ID NO 150)

NOVl3d (SEQ ID NO 152)

NOVl3e (SEQ ID NO 154)

NOVl3f (SEQ ID NO 156)

NOVl3g (SEQ ID NO 158)

Further analysis of the NOVl 3a protein yielded the following properties shown in Table 13C.

Table 13C. Protein Sequence Properties NOV13a

SignalP analysis: 1 Cleavage site between residues 24 and 25

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 3; pos.chg 1; neg.chg 1 H-region: length 18; peak value 10.51 PSG score: 6.11

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -0.88 possible cleavage site: between 23 and 24

»> Seems to have a cleavable signal peptide (1 to 23)

ALOM: Klein et al's method for TM region allocation Init position for calculation: 24

Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 1.27 (at 188) ALOM score: 1.27 (number of TMSs: 0)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 11 Charge difference: 4.0 C( 5.0) - N( 1.0) C > N: C- erminal side will be inside

>»Caution: Inconsistent mtop result with signal peptide MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Momen (75) : 8.86 Hyd Moment(95): 9.72 G content: 2 D/E content: 2 S/T content: 0 Score: -7.20

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 49 ART | HP

NDCDISC: discrimination of nuclear localization signals pat4: none p t7 : none bipartite: none content of basic residues: 11.4% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals: none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none RNA-binding motif: none

Actinάn-type actin- -binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Prenylation motif: none memYQRL: transport motif from cell surface to Golgi : none

Tyrosines in the tail : none

NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination

Prediction: nuclear

Reliability: 76.7

COIL: Lupas 's algorithm to detect coiled-coil regions

925 M 0.82

926 F 0.94

927 Q 1.00

928 N 1.00

929 L 1.00

930 A 1.00

931 N 1.00

932 E 1.00

933 E 1.00

934 V 1.00

935 R 1.00

936 K 1.00

937 L 1.00

938 T 1.00

939 Q 1.00

940 R 1.00

941 L 1.00

942 E 1.00

943 E 1.00

944 M 1.00

945 T 1.00

946 Q 1.00

947 R 1.00

948 M 1.00

949 E 1.00

950 A 1.00

951 L 1.00

952 E 1.00

953 N 1.00 954 R 1.00

955 L 1.00

956 R 1.00

957 Y 1.00

958 R 0.99 total: 34 residues

Final Results (k = 9/23) :

60.9 % : nuclear

17.4 %: mitochondrial

8.7 % : cytoplasmic

8.7 %: extracellular, including cell wall

4.3 %: peroxisomal

» prediction for CG51018-01 is nuc (k=23)

A search of the NOVl 3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13D.

In a BLAST search of public sequence databases, the NOVl 3a protein was found to have homology to the proteins shown in the BLASTP data in Table 13E.

PFam analysis predicts that the NOVl 3a protein contains the domains shown in the Table 13F.

Example 14.

The NOVl 4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A.

Table 14A. NOV14 Sequence Analysis

NOV14a, CG51051-07 SEQ ID NO: 161 1495 bp

DNA Sequence jORF Start: ATG at 46 lθ stop?TAG at 1486

TCAAGCTCTGCTTTAGTTTCCAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTC

GATTCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATG ATTTGTGTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAA TCCACGGACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCC TGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGC TGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCC ACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCT AACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCG ATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGAT CCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAAC AGGGTATACAACAAATAGCAAAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGAC CTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTT ACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACA CTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATG CCACTGTATGTGTGTATGACAACAGCAPA.TTGACATGCGAATGTGAGCACAACACTACAGGTCCAGAC TGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAA AGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATAT GGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACA GTTTCTTCTGTTCAAGTTGCAAACCACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCA GAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCG AGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGC TCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCAC

NOV14a, CG51051-07 SEQ ID NO: 162 480 aa MW at 53945. OkD Protein Sequence

I^LSRFLSIHAL VTVSSVMQPYPLV GHYDLCKTQIYTEEGKV DYMACQPΞSTDMTKYLKV LDPP DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPEL FDFEGRHPSTFWQSATWKEYPKPLQVNITL S SKTIELTDNIVITFESGRPDQMILEKSLDYGRT QPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEI DRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLHA VC /YDNS LTCECEHNTTGPDCGKCK NYQGRP SP GSYLPIP GTAN CIPSISSIGNPPKFls i PNISSLEVSNPKQVAP IALSTVSSVQVANHKRANVC DNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF

NOV14b, CG51051-14 SEQ ID NO: 163 1369 bp

DNA Sequence JQRF Star ATG at 46 jORF StopTTAG at 1360

TCAAGCTCTGCTTTAGTTTCCAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTC

GATTCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATG ATTTGTGTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAA TCCACGGACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCC TGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGC TGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCC ACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCT AACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCG ATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGAT CCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAAC AGGGTATACAACAAATAGCAAAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGAC CTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTT ACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACA CTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATG CCACTGTATGTGTGTATGACAACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGAC TGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAA AGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTACGAATGTCTGCGACAACGAGCTCC TGCACTGCCAGJ^ACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGC ATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCC CCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCT AGGTGTCAC

NOV14b, CG51051-14 SEQ ID NO: 164 438 aa MW at 49339.7kD Protein Sequence

MYLSRFLSIHAL VTVSSVMQPYPLV GHYDLCKTQIYTEEG VWDY ACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTF QSAT KEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRT QPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNS IIHFEIKDRFAFFAGPRLRNMASLYGQLDTTK LRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDI VRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKK YQGRPWSP GSYLPIPKGTANTCIPSISSIGT VCDNELI^CQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCG SDSGQGAPPHGSPALLLLTTLLGTASPLVF

NOV14c, 254537195 SEQ ID NO: 165 1398 bp

DNA Sequence (oRF StartTat ϊ fORF StopTend of sequence

AGATCTGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACAC GGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGA AAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAAT CCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTT TGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTC TCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTT GAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTA TCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCAC AGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATA ATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCT CTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGC TGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATC TCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAG CAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATC AGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCC AGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGT TTCTAACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACC ACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAAC GTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGG CAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCA CGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCCTCGAG

NO V 14c, 254537195 SEQ ID NO: 166 466 aa MW at 52338.1kD Protein Sequence

RSV QPYPLV GHYDLCKTQIYTEEGi AroYMACQPESTDMTKYLKVKLDPPDITCGDPPETFCAMGN PYMCNNECDASTPELAHPPELMFDFEGRHPSTF QSATWKEYP PLQVNITLSWSKTIELTDNIVITF ESGRPDQMILEKSLDYGRT QPYQYYATDCLDAFHMDPKSVKDLSQHTVLEIICTEEYSTGYTT SKI IHFEIFJJRFAFFAGPRLPJJMASLYGQLDTT KLRDFFTVTDLRIRLLRPAVGEIFVDELHLARYFYAI SDIKVRGRCKCNLHAVCVYDNSKLTCECEHNTTGPDCGKCIOX YQGRP SPGSYLPIPKGTANTCIP SISSIGNPPKF RIWPNISSLΞVSNPKQVAP LALSTVSSVQVANHKRANVCDNELLHCQNGGTCHNN VRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTASPLVFLE

NOV14d, 254537282 SEQ ID NO: 167 750 bp

DNA Sequence ORF Start: at 1 JORF Stop: end of sequence

AGATCTTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATAT TACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTG ATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATCCCTCC ACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTGTCTTG GAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCAAATGA TCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACTGCTTA GATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATCATTTG CACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCACTTTGAAATCAAAGACAGGT TCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAG AAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGGGAAAT ATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGGACTCG AG

NOV14d, 254537282 SEQ ID NO: 168 250 aa MW at 28958.6kD Protein Sequence

RSCQPESTDMTKYLKVKLDPPDITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPS TF QSAT EYPKPLQVNITLS SKTIELTDNIVITFESGRPDQMILEKSLDYGRT QPYQYYATDCL DAFH DPKSVKDLSQHTVLEIICTEEYSTGYTTNSKIIHFEI DRFAFFAGPRLRN ASLYGQLDTTK KLRDFFTVTDLRIRLLRPAVGEIFVDELHLARYFYAISDIKVRGLE

NOV14e, CG51051-09 SEQ ID NO: 169 1480 bp DNA Sequence ORF Start: ATG at 26 ORF Stop: end of sequence

AGGCTCCGCGGCCGCCCCCTTCACCATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA

CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTA TCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTT GAGGTTTCTAACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGC AAACCACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACA ACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAG GCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCT GACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTC

|NOV14e, CG51051-09 SEQ ID NO: 170 480 aa MW t 53945.0kD Protein Sequence

MYLSRFLSIHALVTVSSV QPYPLV GHYDLCKTQIYTEEG VWDYMACQPESTD TKYLKVKLDPP

DITCGDPPETFCAMGNPY CNNECDASTPELAHPPELMFDFEGRHPSTFWQSAT KEYPKPLQVNITL

S SKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHiyiDP SVKDLSQHTVLEI

ICTEEYSTGYTTNSKIIHFEIIΦRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG

EIFVDELHIARYFYAISDIKVRGRCKCWLimTVCVYDNSKLTCECEHNTTGPDCGKCKK-STYQGRP S

GSYLPIPKGTANTCIPSISSIGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANHKRA VC

DlffiLLHCQNGGTCHNNVRCLCPAAYTGlLCE LRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS

PLVF

NOV14£ 304965116 SEQ ID NO: 171 1465 bp

DNA Sequence ORF Start: at 2 [ORF Stop: end of sequence

CACCAGATCTCCCACCATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTACGGTGTCCT CAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAA GAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGT GAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCT ACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGAT TTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCA GGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAAT CTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAG TATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCA TACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCJ^AAATAATCC ACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTAC GGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTT AAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAG ACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAA TTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGG CCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTA TTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCT AACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAA GAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGC GCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGC TGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCT GCTGGGAACCGCCAGCCCCCTGGTGTTCCTCGAGGGC

NOV14f, 304965116 SEQ ID NO: 172 488 aa MW at 54786.9kD Protein Sequence

TRSPTMYLSRFLSIHAL TVSSVMQPYPLVWGHYDLCKTQIYTEEG Vli'7DYMACQPESTDMTKYLKV KLDPPDITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQ VNITLSWS TIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQH VLEIICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTK LRDFFTVTDLRIRLL iRPAVGEIFVDELHLARYFYAISDIKVRGRCKC]sTLHA VCVYDNSKLTCECEHmTGPDCGKCK NYQG RPWSPGSYLPIPKGTANTCIPSISS GNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANHK RANVCDNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTL LGTASPLVFLEG NOV14g, 273711018 SEQ ID NO: 173 2818 bp

DNA Sequence ORF Start: at 2 ORF Stop: end of sequence

CACCAGATCTAGGCAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGC AGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCT CGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAATTCTTGGA CATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAGTTCTCCC TCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTCCACGGGC ACCATGACTGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGGCCCGGCC CCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCG AGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGTAGACTTC AACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATTTCAGCCA GATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACCCTGGAGC ATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGGCTACATT CTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACTGTGAGCA GCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGGATG GGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTGTGTAAAT GCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAACGTGCAC AAAGATAGACTACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGATGATTCCT ATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGATCAACTAC TGTGCACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACTGCCGCTG CCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCACAGCAGG ACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTC CTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGA ATACTCCTGTGTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTCCGCAGCG ATGGGAAGACGTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTCGTGTGTA AGCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAAAAACCTG CAGAAGGAAAGATGTCTGCCAAGCTATAGACCATGGCTGTGAACACATTTGTGTGAACAGTGACGACT CATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAGGAAGGAT ^TCTGCAAATCAACCCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACATCTGCAA iATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGCCCAATTG ACCTGGTCTTTGTGATCGATGGATCCAAGAGTCTTGGAGAAGAGAATTTTGAGGTCGTGAAGCAGTTT GTCACTGGAATTATAGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTGCAGTATTC CACACAGGTCCACACAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAAGCCGTGG CCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGAGAGAAGT TTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGTTCACCGA CGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATGGTATCACTATGTATG CTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAACAAGCAT CTCTTCTATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAGAAAGGCATCTGTGA AGCTCTAGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTCCAACAGC CAACAGAATCTGAGCCAGTCACCATAAATATCCAAGACCTACTTTCCTGTTCTAATTTTGCAGTGCAA CACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACΑAAAGCTTTCCCATTCAACAAAACC TTCAGGAAGCCCTTTGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTCCAGAACC TTGCAAACGAAGAAGTΪvAGAAΑATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGAAGCCCTG GAAAATCGCCTGAGATACAGAGTCGACGGC

NOV14g, 273711018 SEQ ID NO: 174 939 aa MW at 104995.2kD Protein Sequence

TRSRQRSRGRSISRGRHARTHPQTALLESSCE3OTCRADLVFIIDSSRSV THDYAKVKEFIVDILQFLD IGPDVTRVGLLQYGSIVKNEFSLKTFKRKSEVERAVKR RHLSTGT TGLAIQYALNIAFSEAEGARP LRENVPRVI IVTDGRPQDSVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQ IETLTSVFQKKLCTAH CSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQ LCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDEKTCT KIDYCASSlrøGCQHECVlsrrDDSYSCHCLKGFTLNPϋKKTCRRINYCAIJvTKPGCEHECVNMEESYΥCRC HRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKTCSRVDYCLLSDHGCE YSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCVSSEDSFVCQCFEGYILREDGKTC RRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAEDGKRCRRKDVCKSTHHGCEHICVNNGNSYICK CSEGFVLAEDGRRCKKCTEGPIDLVFVIDGSKSLGEENFEWKQFVTGIIDSLTISPKAARVGLLQYS TQVHTEFTLRNFNSAKDMKKAVAHMKYMGKGSMTGIJALKHMFERSFTQGEGARPLSTRVPRAAIVFTD GRAQDDVSE ASKAKJ STGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICE ALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFEEDNLLRSTQKLSHSTKP SGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRMEALE10RLRYRVDG

NOV14h, 273711053 SEQ IDNO: 175 2347 bp DNA Sequence ORF Start: at 2 ORF Stop: end ofsequence

CACCAGATCTAGGCAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGC AGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCT CGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAATTCTTGGA CATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAGTTCTCCC TCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTCCACGGGC ACCATGACCGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGGCCCGGCC CCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCG AGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGTAGACTTC AACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATTTCAGCCA GATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACCCTGGAGC ATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGGCTACATT CTCAACTCGGATCAGACGACΓTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACTGTGAGCA GCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGGATG GGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTGTGTAAAT GCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAACGTGCAC AAAGATAGACTACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGATGATTCCT ATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGATCAACTAC TGTGCACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACTGCCGCTG CCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCACAGCAGG ACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTC CTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGA ATACTCCTGTGTCAACATGGACAGATCCTTTGCCΓGTCAGΓGΓCCTGAGGGACACGTGCTCCGCAGCG ATGGGAAGACGTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTCGTGTGTA AGCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAAAAACCTG CAGAAGGAAAGATGTCTGCCAAGCTATAGACCATGGCTGTGAACACATTTGTGTGAACAGTGACGACT CATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAGGAAGGAT GTCTGCAAATCAACCCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACATCTGCAA |ATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAGTATCACTATGTATGCTGTTG GGGTAGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAACAAGCATCTCTTC ITATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAGAAAGGCATCTGTGAAGCTCT ;AGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTCCAACAGCCAACAG TGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAACA AAACCTTCAGGAAGCCCTTTGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTCCA GAACCTTGCAAACGAAGAAGTAAGAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGAAG CCCTGGAAAATCGCCTGAGATACAGAGTCGACGGC

NOV14h, 273711053 SEQ ID NO: 176 782 aa MW at 87838.8kD Protein Sequence

TRSRQRSRGRSISRGRHARTHPQTALLESSCENKRADLVFIIDSSRSVNTHDYAKVKEFIV ILQFLD IGPDVTRVGLLQYGSTVIOVTEFSLKTFKRKSEVERAVKRMRHLSTGT TGLAIQYALNIAFSEAEGARP LRENVPRVIMIVTDGRPQDSVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQ IETLTSVFQKKLCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQ LCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDEKTCT KIDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNMEESYYCRC HRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKTCSRVDYCLLSDHGCE YSCWMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCΞHSCVSSEDSFVCQCFEGYILREDGKTC RKDVCQ IDHGCEHIC SDDSYTCEC EGF AEDGRC RKIVC S HHGCΞHICNNGNS IC CSEGFVIJffiDGRRCKSITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEAL EDSDGRQDSPAGELPKTVQQPTVQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQ NLA ΞEVRKLTQRLEE TQRMEALENRLRYRVDG

NOV14i, 274051275 SEQ ID NO: 177 2761 bp DNA Sequence ORF Start: at 2 JORF Stop: end of sequence

CACCAGATCTAGGCAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGC AGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCT CGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAATTCTTGGA CATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAGTTCTCCC TCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTCCACGGGC ACCATGACCGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGGCCCGGCC CCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCG AGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGTAGACTTC AACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATTTCAGCCA GATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACCCTGGAGC ATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGGCTACATT CTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACTGTGAGCA GCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGGATG GGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTGTGTAAAT GCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAACGTGCAC AAAGATAGACTACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGATGATTCCT ATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGATCAACTAC TGTGCACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACTGCCGCTG CCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCACAGCAGG ACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTC CTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGA ATACTCCTGTGTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTCCGCAGCG ATGGGAAGACGTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTCGTGTGTA AGCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAAAAACCTG CAGAAGGAAAGATGTCTGCCAAGCTATAGACCATGGCTGTG_AACACATTTGTGTGAACAGTGACGACT CATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAGGAAGGAT. GTCTGCAAATCAACCCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACATCTGCAA ATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGCCCAATTG _IACCTGGTCTTTGTGATCGATGGATCCAAGAGTCTTGGAGAAGAGAATTTTGAGGTCGTGAAGCAGTTT GTCACTGGAATTATAGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCCAGTATTC CACACAGGTCCACACAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAAGCCGTGG CCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGAGAGAAGT TTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGTTCACCGA CGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATGGTATCACTATGTATG ICTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAACAAGCAT CTCTTCTATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAGAAAGGCATCTGTGA AGCTCTAGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTCCAACAGC CAACAGTGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCAT TCAACAAAACCTTCAGGAAGCCCTTTGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAAT GTTCCAGAACCTTGCAAACGAAGAAGTAAGAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAA ITGGAAGCCCTGGAAAATCGCCTGAGATACAGAGTCGACGGC

NOVHi, 274051275 SEQ ID NO: 178 920 aa MW at l02933.0kD Protein Sequence

TRSRQRSRGRSISRGRHARTHPQTALLESSCEIΩRADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLD IGPDVTRVGLLQYGSTVKNEFSLKTFKRKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARP LRE VPRVIMIVTDGRPQDSVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQ IETLTSVFQKKLCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQ LCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECV ADGSYLCQCHEGFALNPDEKTCT KIDYCASSNHGCQHECVNTDDSYSCHCLKGFTIiNPDKKTCRRINYCALNKPGCEHECVNMEESYYCRC HRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKTCSRVDYCLLSDHGCE YSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCVSSEDSFVCQCFEGYILREDGKTC RRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAEDGKRCRRKDVCKSTHHGCEHICVNNGNSYICK CSEGFVLAEDGRRGKKCTEGPIDLVFVIDGSKSLGEENFΞWKQFVTGIIDSLTISPKAARVGLLQYS TQVHTEFTLP^FNSAKDMKKAVAH KYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTD GRAQDDVSEWASKAKANGIT yAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICE ALEDSDGRQDSPAGELPKTVQQP VQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIM FQNLANEE^'VRKLTQRLEEMTQRMEALENRLRYRVDG

NOV14J, CG51051-01 SEQ ID NO: 179 1908 bp

DNA Sequence fc>RF Start: ATG at 230 (ORF Stop: TAG at 1670

GGCTTCCACCAAAGTCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTGGTTTTGG

IGATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCATACAT lACATATGTGTATATATATGTAAACTAGACAAAGATCGCAGATCATAAAGCAAGCTCTGCTTTAGTTTC

CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA

CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTA TCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTT GAGGTTTCTAACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGC AAACCACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACA ACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAG GCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCT GACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCACCTCCAGCCACACCGGACGGGC CTGTGCCGTGGGGAAGCAGACACAACCCAAACATTTGCTACTAACATAGGAAACACACACATACAGAC

ACCCCCACTCAGACAGTGTACAAACTAAGAAGGCCTAACTGAACTAAGCCATATTTATCACCCGTGGA

CAGCACATCCGAGTCAGGACTGTTAATTTCTGACTCCAGAGGAGTTGGCAGCTGTTGATATTATCACT

GCAA

NOV14j, CG51051-01 SEQ ID NO: 180 480 aa MW at 53945.0 D Protein Sequence

MYLSRFLSIHALWVTVSSV QPYPLV GHYDLCKTQIYTEEGKV DYMACQPΞSTD TKYLKVKLDPP DITCGDPPETFCAMGNPY CNNECDASTPELAHPPELMFDFEGRHPSTF QSAT KEYPKPLQVNITL SWSKTIΞLTDNIVITFESGRPDQMILEKSLDYGRT QPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHIARYFYAISDIKVRGRCKCNLHA VC tYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSP GSYLPIPKGTANTCIPSISSIGNPPKFNRI PNISSLEVSNPKQVAPKIJALSTVSSVQVANHKRAIVTVC DNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF

NOV14k, CG51051-02 SEQ ID NO: 181 1343 bp DNA Sequence ORF Start: ATG at 18 ORF Stop: End of Sequence

ATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTACGGTGTCC

TCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGA

AGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAG

TGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCC

TACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGA

TTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCC

AGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAA

TCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCA

GTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGC

ATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATC

CACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTA

CGGACAGCTGGATACAACCAAGAAACTCAGGGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGT

TAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCA

GACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAA

ATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTACCAGG

GCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCGCTGCAAATACCTGTATCCCCAGT

ATTTCCAGTATTGGTAAGTGTTATTGTAACCCTTTGGGCTCAATCCATGATCGTTGTAATGGCTCAGG

ATTTTGTGAGTGTAAGACTGGAACAACAGGGCCTAAGTGTGATGAGTGTCTGCCGGGCAATTCCTGGC

ACTACGGCTGTCAACCGAATGTCTGCGACAACGAGCTCCTGCCACCATGTATTTGTCAAGATTCCTGT

CGATTCTATCTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCTCGAGAAGGG

NOV14k, CG51051-02 SEQ ID NO: 182 442 aa MW at 50335.9kD Protein Sequence

MYLSRFLSimVLWVTVSSVMQPYPLV GHYDLCKTQIYTEEGKVra)YMACQPESTDMTKYLKVKLDPP

DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPEL FDFEGRHPSTFWQSATWKEYPKPLQVNITL

S SKTIELTDNIVITFESGRPDQMILEKSLDYGRT QPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI

ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG

EIFVDELHLAΛYFYAISDII^GRCKCNLHATVC^^

GSYLPIPKGAANTCIPSISSIGKCYCNPLGSIHDRCNGSGFCECKTGTTGPKCDECLPGNSWHYGCQP

NVCDNΞLLPPCICQDSCRFYLWPGRAPARLPREG

INOV141, CG51051-03 SEQ ID NO: 183 1544 bp

DNA Sequence ORF Start: ATG at 230 ORF Stop: TAG at 1517

GGCTTCCACCAAAGTCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTGGTTTTGG

GATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCATACAT

ACATATGTGTATATATATGTAAACTAGACAAAGATCGCAGATCATAAAGCAAGCTCTGCTTTAGTTTC

CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGCGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTCGA ATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTG TGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTC CGACTCTGGTCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAA CCGCCAGCCCCCTGGTGTTTTAGGTGTCACCTCCAGCCACACCGGACG

NOV141, CG51051-03 SEQ ID NO: 184 429 aa MW at 48439.7kD Protein Sequence

^RXLS F S IH V VSSVMQPYPLV GHYD CKTQI TEEGKV DYMACQ ESTDMTK K D P

DITCGDPPETFCAMGNPYMC NECDASTPEIIAHPPELMFDFEGRHPSTF QSATWKEYPKPLQVNITL

SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRT QPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI

ICTEEYSTGYTTNSKIIHFΞIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFF VTDLRIRLLRPAVG

EIFVDELHIΛRYFYAISDIKARGRCKCNLHATVCVYDN^

GSYLPIPKGTANTS CDNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPP

HGS PALLLLTTLLG AS PLVF

NOV14m, CG51051-04 SEQ ID NO: 185 1771 bp DNA Sequence ORF Start: ATG at 230 ORF Stop: TAG at 1544

GGCTTCCACCAAAGTCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTGGTTTTGG

GATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCATACAT

IACATATGTGTATATATATGTAAACTAGACAAAGATCGCAGATCATAAAGCAAGCTCTGCTTTAGTTTC

CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA

CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTA TCCCCAGTATTTCCAGTATTGGTACGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGG ACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCG GTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGC TGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCACCTCCAGCCACA CCGGACGGGCCTGTGCCGTGGGGAAGCAGACACAACCCAAACATTTGCTACTAACATAGGAAACACAC ACATACAGACACCCCCACTCAGACAGTGTACAAACTAAGAAGGCCTAACTGAACTAAGCCATATTTAT CACCCGTGGACAGCACATCCGAGTCAAGACTGTTAATTTCTGACTCCAGAGGAGTTGGCAGCTGTTGA :TAT

NOV14m, CG51051-04 SEQ ID NO: 186 438 aa MW at 49339.7kD Protein Sequence

MYLSRFLSIHAL VTVSSVMQPYPLV GHYDLCKTQIYTEEGKVlrøYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLHATVCv/YDNSKLTCECEHl^TGPDCGKCKKYQGRPWSP GSYLPIPKGTANTCIPSISSIGT1WCDNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCG SDSGQGAPPHGSPALLLLTTLLGTASPLVF

NOV14n, CG51051-05 SEQ ID NO: 187 1771 bp DNA Sequence ORF Start: ATG at 230 ORF Stop: TAG at 1544

GGCTTCCACCAAAGTCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTGGTTTTGG

GATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCATACAT

IACATATGTGTATATATATGTAAACTAGACAAAGATCGCAGATCATAAAGCAAGCTCTGCTTTAGTTTC

CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA

CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTA TCCCCAGTATTTCCAGTATTGGTACGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGG ACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCG GTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGC TGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCACCTCCAGCCACA CCGGACGGGCCTGTGCCGTGGGGAAGCAGACACAACCCAAACATTTGCTACTAACATAGGAAACACAC

ACATACAGACACCCCCACTCAGACAGTGTACAAACTAAGAAGGCCTAACTGAACTAAGCCATATTTAT

CACCCGTGGACAGCACATCCGAGTCAAGACTGTTAATTTCTGACTCCAGAGGAGTTGGCAGCTGTTGA

TAT

NOV14n, CG51051-05 SEQ ID NO: 188 438 aa MW at 49339.7kD Protein Sequence j nTLSRFLSIHALWVTVSSλ QPYPLVWGHΥDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP

DITCGDPPETFCAMGNPY CNNECDASTPELAHPPELMFDFEGRHPSTF QSAT KEYPKPLQVNITL

S SKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHI^PKSVKDLSQHTVLEI

ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG

EIFVDELHLARYFYAISDlKVRGRCKCNLHATV TYDNSK^^

GS LP I PKGTANTCI PS I S S IGTNVCDlffiLLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGS CG

SDSGQGAPPHGSPALLLLTTLLGTAS PLVF

NOV14o, CG51051-06 SEQ ID NO: 189 1290 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: end of sequence

ATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGCTACGGTGTCCTCAGTGATGCAGCCCTA CCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGG ATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCG GATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGA GTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATC CCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTG TCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCA AATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACT GCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATC ATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCACTTTGAAATCAAAGA CAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAA CCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGG GAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGG AAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAATTGACATGCGAATGTG AGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCA GGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAC GAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCC TGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGC TCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCTCGAGAAGGGCAATTCCACCACACTGGAC

NOV14o, CG51051-06 SEQ ID NO: 190 430 aa MW at 48548.6kD Protein Sequence

MYLSRFLSIHALWATVSSVMQPYPLV GHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNIIECDASTPELAHPPELMFDFEGRHPSTF QSATWKEYPKPLQVNITL SWSK IE DNIVITFESG PDQMI E S DYGRTW P Q TDC D FH ©PKS ^DLSQHT L₁EI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRMMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHI-Z YFYAISDIKVRGRCKCNLHATVCVYBNS IiTCECEHNTTGPDCGKCKKNYQGRP SP GSYLPIPKGTANTCIPSISSIGTNVCDNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEΞAGSCG SDSGQGAPPHGSLEKGNSTTLD

NOV14p, CG51051-08 SEQ ID NO: 191 1837 bp

DNA Sequence JORF Start: ATG at 230 jORF StopTlAG at 1610

GGCTTCCACCAAAGTCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTGGTTTTGG

GATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCATACAT

ACATATGTGTATATATATGTAAACTAGACAAAGATCGCAGATCATAAAGCAAGCTCTGCTTTAGTTTC

CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA

CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTA TCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTT GAGGTTTCTAACCCAAAACAAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGAC GTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGT GCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTG CTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCACCTCCAGCCACACC GGACGGGCCTGTGCCGTGGGGAAGCAGACACAACCCAAACATTTGCTACTAACATAGGAAACACACAC

ATACAGACACCCCCACTCAGACAGTGTACAAACTAAGAAGGCCTAACTGAACTAAGCCATATTTATCA

CCCGTGGACAGCACATCCGAGTCAAGACTGTTAATTTCTGACTCCAGAGGAGTTGGCAGCTGTTGATA

NOV14p, CG51051-08 SEQ ID NO: 192 460 aa MW at 51857.6kD Protein Sequence MYLSRFLSIHJΛWVTVSSV QPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPY CNNECDASTPELAHPPELMFDFEGRHPSTFWQSAT KEYPKPLQVNITL S SKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI I CTEEYSTGYTTNSKI HFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG El FVDELHLARYF YAI SD I VRGRCKCNLHATVCVYDNS KLTCECEHNTTGPDCGKCKKNYQGRPWSP GSYLPIPKGTANTCIPSISSIGNPPKFls iWPNISSLEVSNPKQANVCDNELLHCQNGGTCHNNVRCL CPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTASPLVF

NOV14q, CG51051-10 SEQ ID NO: 193 1426 bp DNA Sequence ORF Start: at 29 ORF Stop: end of sequence

AGGCTCCGCGGCCGCCCCCTTCACCGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGT

GTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACG GACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGAC GTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCAC ACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGG AAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGA CAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATG GACGAACATGGCAGCCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAA TCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTA TACAACAAATAGCAAAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCC TACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTC ACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGC ACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTG TATGTGTGTATGACAACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGG AAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCAC TGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGA ATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCT TCTGTTCAAGTTGCAAACCACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGG AGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGC TGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCA GCGCTGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCAAGGGTGGGCGCGCC

NOV14q, CG51051-10 SEQ ID NO: 194 462 aa MW t 51852.6kD Protein Sequence

VMQPYPLVWGHYDLCKTQIYTEEGKV DYMACQPESTD TKYLKVKLDPPDITCGDPPETFCAMGNPY MCNNECDASTPELAHPPEL FDFEGRHPSTF QSAT KEYPKPLQVNITLS SKTIELTDNIVITFES RPDQMI ΞKS DYGRT QPYQ DCLDAFH^roPKSVKD SQHTVLEIIC EEYS G TNSKIIH FEIKDRFAFFAGPRLRNiLASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVGEIFVDELHLARYFYAISD IK GRCKCl^HATVCVYDNSKLTCECEHHTTGPDCGKCKKNYQGRP SPGSYLPIPKGTANTCIPSI SSIGNPPKFl^IWPNISSLEVSNPKQVAPKIJ ^STVSSVQVANHKRANVCDNELLHCQNGGTCHNNVR CLCPAAYTGI CEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTASPLVF SfOV14r, CGS 1051-11 ^" s^ ID OTr95^~~]778 bp

DNA Sequence )ORF Start: at 2 JORF StopTend of sequence

GGCTCCGCGGCCGCCCCCTTCACCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGTGA

AACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTAC

ATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATTT

TGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGG

TTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATCT

GGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAGTA

TTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCATA

CGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCAC

TTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGG

ACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAA

GACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGAC

ATAAAGGTGCGAGGAAAGGGTGGGCGCGCC

NOV14r, CG51051-11 SEQ ID Nθ7Ϊ96l259 aa MW at 29645.3kD Protein Sequence GSAAAPFTCQPESTDMTKYLKVKLDPPDITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDF ^GRHPSTF QSAT KEYPKPLQVNITLS SKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQY DC υAFH mPKSV D SQH VLEIIC EEYS GYT NSK IHFEIKDRFAFFAGPR IAS YG QLDTTKKLRDFFTVTDLRIRLLRPAVGEI FVDELHLARYF AI SD I KVRGKGGRA

|NOV14s, CG51051-12 SEQ ID NO: 197 )1452 bp

DNA Sequence ϊ Sta ATG at 7 lORF Stop: end of sequence

AGATCTATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCA

GCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAAGAAGGGAAAG TTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGTGAAACTCGAT CCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAA TAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAA GACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATC ACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCC AGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCA CAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTA GAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCACTTTGAAAT CAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGG ATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCC GTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGT GCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAATTGACATGCG AATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGG AGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTAT TGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAAC AAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAAGAGAGCGAAT GTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTG CCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCG ACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAACC GCCAGCCCCCTGGTGTTC

NOV14s, CG51051-12 SEQ ID NO: 198 480 aa MW at 53945.0kD Protein Sequence

MYLSRFLSIHALV3VTVSSVMQPYPLV GHYDLCKTQIYTEEGKV DYMACQPESTD TKYLKVKLDPP DITCGDPPETPCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTF QSAT KEYPKPLQVNITL S SK E TD IVI FESG PDQ I EKS DYGR WQPYQ YATDC DAFH C)PKSVKD SQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNi LASLYGQl-DTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKC iαsiYQGRPWSP GSYLPIPKGTANTCIPSISSIGNPPKFlNmiWPNISSLEVSNPKQVAPKIJ^STVSSVQVANHKRANVC DNELLHCQNGGTCmiNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF

NOV14t, CG51051-13 SEQ ID NO: 199 750 bp

DNA Sequence foRF Start: at 1 ORF Stop: end of sequence

TGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATAT

TACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTG

ATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATCCCTCC

ACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTGTCTTG

GAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCAAATGA

TCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACTGCTTA

GATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATCATTTG

CACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCACTTTGAAATCAAAGACAGGT

TCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAG

AAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGGGAAAT

ATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGGA

NOV14t, CG51051-13 SEQ ID NO: 200 246 aa MW at 28473.OkD Protein Sequence )

CQPESTDMTKYLKVKLDPPDITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTF WQS_ATWK_EYPKP_LQVNITLSWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDA FHMDPKSVKDLSQHTVLΞIICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKL IRDFFTVTDLRIRLLRPAVGEIFVDELHLARYFYAISDIKVRG

NOV14u, CG51051-15 SEQ ID NO: 201 1465 bp

DNA Sequence JO F Start: ATG at 17 ORF Stop: end of sequence

CACCAGATCTCCCACCATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTACGGTGTCCT

_CAGT_GATGCAGCCC_TACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAA GAAGGGAAAGTTTGGGATTACATGGCCTGCCAGc'cGGAATCCACGGACATGACAAAATATCTGAAAGT GAA_ACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCT _ACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGAT TTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCA GG_TT_AAC_ATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAAT CTGGGCG_TCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAG _TATT_ATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCA _TACGGTC_TTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCC _ACT_TTGA_AATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTAC _GGA_CAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTT _AA_GACCA_GCCGT_TGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAG _ACATA_AAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAA TT_GAC_ATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGG _CC_GACCT_TGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTA _TTT_CCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCT A_ACCC_AA_AACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAA GA_GAGCG_AATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGC _GCT_GCC_TGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGC _TGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCT GCTGGGAACCGCCAGCCCCCTGGTGTTC

NOV14u, CG51051-15 SEQ ID NO: 202 480 aa MW at 53945.0kD Protein Sequence

MY_LSRFLSIHALWVTVSSVMQPYPLV GHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP _DI_TCG_DP_PETFCAMGNPYMCNNECDASTPΞLAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIE_LTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI _IC_TEEYS_TGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG ΞI_FVDELHLARYFYAISDIKVRGRCKCNLK^TVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSP GS_YLPIPKGTANTCIPSISSIGNPPKFNRIWPNISSLEVSNPKQVAPLALSTVSSVQVANHKRANVC _DN_ELLH_CQNGGTCHNtsTVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF

NOV14v, CG51051-16 SEQ ID NO: 203 1467 bp

DNA Sequence ORF Start: ATG at 16 ORF Stop: TAG at 1456

CACCGCGGCCGCACCATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTACGGTGTCCTC

_AG_TG_ATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAAG _AA_GGG_AAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGTG AAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTA CA_TG_TG_CAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATT TT_GAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAG GT_TAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATC TG_GG_CG_TCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAGT AT_TATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCAT AC_GGTC_TTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCA CT_TTGA_AATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACG GA_CAGC_TGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTA AG_ACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGA _CA_TA_AA_GGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAAT T_GACAT_GCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGGC CG_ACCT_TGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTAT TTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTA ACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAAG AGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCG CTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCT GCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTG CTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTCGACGGC

NON14v, CG51051-16 SEQ ID NO: 204 480 aa MW at 53945.0kD Protein Sequence lytYLSRFLSIHiUj VTVSSV QPYPLVWGHYDLCKTQIYTEEGIWWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPEI.AHPPELMFDFEGRHPSTF QSATWKEYPKPLQVNITL S SKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEH1STTTGPDCGKCKKΪIYQGRPWSP GSYLPI KGTANTC I PS I S S IGNPPKFNRIWPNI S SLEVSNPKQVAPKLALSTVS SVQVANHKRANVC DNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF

NOV14w, 13380736 SNP for SEQ ID NO: 1495 bp, SNP: 217 A/G CG51051-07 205 DNA Sequence ORF Start: ORF Stop: TAG at 1486 ATG at 46 CAAGCTCTGCTTTAGTTTCCAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGAT

TCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGT GTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGAC ATGGCAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTG TGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTG AGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCC AAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTAC CTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCT ATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAG CATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCA CTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGAC AGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCA GCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGG GCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAATTGACATGCGAAT GTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCA GGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAATCC TCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAAGTTGCTCCCA AATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAAGAGAGCGAATGTCTGCGACAACGAG CTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGG CATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCC CGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTG TCAC

NOV14w, 13380736 SNP for SEQ ID NO: 480 aa SNP: Thr to Ala at position 58 CG51051-07 206 Protein Sequence

IvrYLSRFLSIHAL VTVSSVMQPYPLV GHYOLCKTQIYTEEGKVWDYl^CQPESTDi ^YLKVKLDPPDIT CGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTF QSATWKEYPKPLQVNITLS SKTI ELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEIICTEEYSTG YTTNSKIIHFΞIKDRFAFFAGPRLRH ASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVGEIFVDELHLARY FYAI SD IKVRGRCKCNLKATVCrVYDNS LTCECΞHNTTGPDCGKCKKNYQGRP S PGSYLPI PKGTANTC I PSISSIGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANHIOΪANVCDNELLHCQNGGTCH2ΛNVR CLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTASPLVF

NOV14x, 13380734 SNP for SEQ ID NO: 207 1495 bp, SNP: 872 T/G CG51051-07 ORF Start: ATG at 46 ORF Stop: TAG at 1486 DNA Sequence

TCAAGCTCTGCTTTAGTTTCCAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGAT

TCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGT GTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGAC ATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTG TGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTG AGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCC AAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTAC CTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCT ATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAG CATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCA CTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGAC AGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCA GCCGTTGGGGAAATATTTGGAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGT GCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAATTGACATGCGAAT GTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCA GGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAATCC TCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAAGTTGCTCCCA, AATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAAGAGAGCGAATGTCTGCGACAACGAG CTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGG CATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCC CGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTG TCAC

NOV14x, 13380734 SNP for SEQ ID NO: 480 aa SNP: Val to Gly at position 276 CG51051-07 208 Protein Sequence

MYLSRFLSIHALWVTVSSV QPYPLVWGHYDLCKTQIYTEEGKVW)YX^CQPESTDMTKYLKVKLDPPDIT CGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSAT KEYPKPLQVNITLS SKTI ELTDNIVITFESGRPDQMILEKSLDYGRT QPYQYYATDCLDAFHMDPKSVKDLSQHTVLEIICTEEYSTG YTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVGEIFGDELHLARY FYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSPGSYLPIPKGTANTCI PSISSIGNPPKFNRI PNISSLEVSNPKQVAPKIJUSTVSSVQVAlsraKRANVCDNELIJΪCQNGGTCHNNVR CLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTASPLVF

NOV14y, 13382329 SNP for SEQ ID NO: 209 |1495 bp SNP: 1448 T/A CG51051-07 ORF Start: ATG at 46 ORF Stop: TAG at 1486 DNA Sequence

TCAAGCTCTGCTTTAGTTTCCAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGAT

TCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGT GTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGAC ATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTG TGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTG AGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCC AAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTAC CTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCT ATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAG CATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCA CTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGAC AGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCA GCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGT GCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAATTGACATGCGAAT GTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCA GGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAATCC TCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAAGTTGCTCCCA AATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAAGAGAGCGAATGTCTGCGACAACGAG CTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGG CATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCC CGCACGGCTCCCCAGCGCTGCTGCTGCAGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTG TCAC

NOVl4y, 13382329 SNP for SEQ ID NO: 480 aa SNP: Leu to Gin at position 468

CG51051-07 210

Protein Sequence

^rYLSRF SIHA V VSSVMQPYP V GHYD CKT IYTEEGKΛ DYMACQPES DMTK KVKLDPPDIT CGDPPETFCA GNPYMCNNECDASTPEIjAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITLSWSKTI ELTDNIVITFESGRPDQMILEKSLDYGRT QPYQYYATDCLDAFHMDPKSVKDLSQHTVLEIICTEEYSTG YTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVGEIFVDΞLHLARY FYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRP SPGSYLPIPKGTANTCI PSISSIGNPPKFMRIWPNISSLEVSNPKQVAPKLALSTVSSVQVAlrø SAjrvCDNELLHCQNGGTCH2ΩWR CLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLQTTLLGTASPLVF

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 14B.

Table 14B. Comparison of the NOV14 protein sequences.

N0V14a MYLSRFLSIHAL VTVSSVMQPYPLV GHYDLCKTQIYTEEGKV DY ACQPEST

N0V14b MYLSRFLSIHALWX^TVSSVMQPYPLVWGHYDLCKTQIYTEEGKV DYMACQPEST

N0V14C RSVMQPYPLVWGHYDLCKTQIYTEEGKV DYMACQPEST

N0V14d RSCQPEST

NOV14e MYLSRFLSIHALWVTVSSV QPYPLVWGHYDLCKTQIYTEEGKV DY ACQPEST

N0V14f TRSPTMYLSRFLSIHALWVTVSSVMQPYPLV GHYDLCKTQIYTEEGKVWDYMACQPEST

N0V14g TRSRQRS-RGRSISRGRHARTHPQTALLESSCENK-RADLVFIID—SSR—SV

N0Vl4h TRSRQRS-RGRSISRGRHARTHPQTALLESSCENK-RADLVFIID—SSR—SV

N0V14i TRSRQRS-RGRSISRGRHARTHPQTALLESSCENK-RADLVFIID—SSR—SV

NOVl4j MYLSRFLSIHAL VTVSSVMQPYPLVWGHYDLCKTQIYTEEGKV DYMACQPEST

NOVl k MYLSRFLSIHAL VTVSSVMQPYPLVWGHYDLCKTQIYTEEGKV DYMACQPEST

NOV141 MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKV DYMACQPEST

NOVl4m MYLSRFLSIHALWVTVSSVMQPYPLV GHYDLCKTQIYTEEGKVWDYMACQPEST

N0V14n YLSRFLSIHAL VTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDY ACQPEST

N0V14O MYLSRFLSIHAL ATVSSVMQPYPLV GHYDLCKTQIYTEEGKV DYMACQPEST

N0Vl4p MYLSRFLSIHALWVTVSSVMQPYPLV GHYDLCKTQIYTEEGKV DYMACQPEST

NOVl4q VMQPYPLV GHYDLCKTQIYTEEGKV DYMACQPEST

NOVl4r GSAAAPFTCQPEST

NOV14S MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLC TQIYTEEGKVWDYMACQPEST

NOVl4t CQPEST

NOV14U MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKV DYMACQPEST

N0V14V MYLSRFLSIHALWVTVSSV QPYPLV GHYDLCKTQIYTEEGKV DYMACQPEST

NOVl4a DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR

NOVl4b DMTKYL VKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR

NQV14C D TKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPEL FDFE-GR

NOVl4d D TKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPEL FDFE-GR

NOVl4e DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR

NOVl4f DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR

NOVl4g NTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFKRKSEVERAVKRMR

NOVl4h NTHDYAKVKΞFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFKR SEVERAVKRMR

NOV14Ϊ NTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFKRKSEVERAVKRMR

NOV14J DMTKYLKVKLDPPDITCG-DP-PETFCA GNPY CNNECDASTPELAHPPELMFDFE-GR

N0V14k DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR

N0V141 DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPEL FDFE-GR NOVl m DMTKYLKVKLDPPDITCG-DP- PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOVl n DMTKYLKVKLDPPDITCG-DP- PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOVl4o DMTKYLKVKLDPPDITCG-DP- PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14p DMTKYLKVKLDPPDITCG-DP-^■PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOVl4q DMTKYLKVKLDPPDITCG-DP- PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOVl r DMTKYLKVKLDPPDITCG-DP- PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOVl s DMTKYLKVKLDPPDITCG-DP- PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOVl4 DMTKYLKVKLDPPDITCG-DP- PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOVl u DMTKYLKVKLDPPDITCG-DP-^■PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOVl4 DMTKYLKVKLDPPDITCG-DP- PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR

NOVl4a HPSTF QSAT KEYPKPLQVNITLS SK-TIELTDNI—VITFES-GRP-D—Q ILEKS NOVl4b HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4c HPSTF QSAT KEYPKPLQVNITLS SK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4d HPSTF QSAT KEYPKPLQVNITLS SK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4e HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl f HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl g HLSTG—TMTG—LAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAAKA NOVl4h HLSTG—TMTG—LAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAAKA NOVl i HLSTG—TMTG—LAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAAKA NOVl j HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl k HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl 1 HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4m HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4n HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4o HPSTF QSAT KEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl p HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4q HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4r HPSTF QSAT KEYPKPLQVNITLS SK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4s HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4t HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4u HPSTF QSAT KEYPKPLQVNITLS SK-TIELTDNI—VITFES-GRP-D—QMILEKS NOVl4 HPSTFWQSATWKEYPKPLQVNITLSWSK-TIELTDNI—VITFES-GRP-D—QMILEKS

NOVl a LDYGRTWQPYQYYATDC— DAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4b LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl c LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4d LDYGRTWQPYQYYATDC— DAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4e LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4f LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl g RDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKKLCTAH-MCS .NOVl4h RDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKKLCTAH-MCS NOVl i RDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKKLCTAH-MCS NOVl4j LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4k LDYGRTWQPYQYYATDC— DAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl41 LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl m LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4n LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4o LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOV14p LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4q LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4r LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4s LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4t LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4u LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4v LDYGRTWQPYQYYATDC—LDAF HMDPKS-VKDLSQHTVLEIICTEEYSTGYTTNS NOVl4a KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14b KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14C KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14d KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14e KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14f KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14g TLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCVNVPGSFVC

NOV14h TLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCVNVPGSFVC

NOV14i TLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCVNVPGSFVC

NOV14J KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOVl k KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV141 KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14m KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14n KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

N0V14O KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

N0V14p KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14q KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14r KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14S KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14t KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14U KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14v KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD

NOV14a ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14b ELHLARYFYAISDIK VRGRCKCNLH— TVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14C ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14d ELHLARYFYAISDIK VRGLE

NOV14e ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14f ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14g QC-YSGYALAE-DGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDEKTCTK

NOVl4h QC-YSGYALAE-DGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDEKTCTK

NOV14i QC-YSGYALAE-DGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDEKTCTK

NOV14J ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14k ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV141 ELHLARYFYAISDIK ARGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOVl4m ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14n ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

N0V14O ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14p ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14q ELHLARYFYAISDIK VRGRCKCNLH— TVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14r ELHLARYFYAISDIK VRGKGGRA

NOV14S ELHLARYFYAISDIK VRGRCKCNLH—ATVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14t ELHLARYFYAISDIK VRG

NOV14U ELHLARYFYAISDIK VRGRCKCNLH— TVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14V ELHLARYFYAISDIK VRGRCKCNLH— TVCVYDNSKLTCEC-EHNTTGPD CGK

NOV14a CKKNYQG-RPW SPGSY-LPIPKG-TANT C—I—PSISSIGNPPKFNRIW

NOVl4b CKKNYQG-RPW SPGSY-LPIPKG-TANT C—I—PSISSIG

NOV14C CKKNYQG-RPW SPGSY-LPIPKG-TANT C—I—PSISSIGNPPKFNRIW

NOV14d

NOVl4e CKKNYQG-RPW SPGSY-LPIPKG-TANT C—I—PSISSIGNPPKFNRIW

NOVl4f CKKNYQG-RPW SPGSY-LPIPKG-TANT C—I—PSISSIGNPPKFNRIW

NOVl4g IDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNME

NOVl4h IDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNME

NOV14i IDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNME OV14J CKKNYQG-RPW SPGSY-LPIPKG-TANT C—I—PSISSIGNPPKFNRIW

NOVl4k CKKNYQG-RPW SPGSY-LPIPKG-AANT C—I—PSISSIG NOVl41 -CKKNYQG-RPW SPGSY-LPIPKG-TAN— NOVl4m -CKKNYQG-RPW SPGSY-LPIPKG-TANT- -—C—I—PSISSIG NOVl4n -CKKNYQG-RPW SPGSY-LPIPKG-TANT- -—C—I—PSISSIG NOVl4o -CKKNYQG-RPW SPGSY-LPIPKG-TANT- —C—I—PSISSIG NOV14p -CKKNYQG-RPW SPGSY-LPIPKG-TANT- —C—I—PSISSIGNPPKFNRIW NOVl4q -CKKNYQG-RPW SPGSY-LPIPKG-TANT- —C—I—PSISSIGNPPKFNRIW NOVl4r NOVl4s CKKNYQG-RPW SPGSY-LPIPKG-TANT C—I—PSISSIGNPPKFNRIW NOV14t NOVl4u CKKNYQG-RPW SPGSY-LPIPKG-TANT C—I—PSISSIGNPPKFNRIW NOV14v CKKNYQG-RPW SPGSY-LPIPKG-TANT C—I—PSISSIGNPPKFNRIW

NOVl4a PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN—ELLHCQNGG- -T NOVl4b TNVCD —ELLHC_QNGG- -T NOVl4c PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN—ELLHCQNGG- -T NOVl4d NOVl4e PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN—ELLHCQNGG T NOVl4f PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN—ELLHCQNGG T NOVl4g ESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKT NOV14h ESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKT NOVl4i ESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKT NOVl4j PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN—ELLHCQNGG T NOVl4k KCYCN—PLGSIHD R NOVl 1 TSNVCD —ELLHCQNGG T NOVl4m TNVCDN—ELLHCQNGG T NOVl4n TNVCDN—ELLHCQNGG T NOVl4o TNVCD —ELLHC_QNGG T NOVl4p PNISSLEVSNPK QANVCD —ELLHCQNGG T NOVl q PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN—ELLHCQNGG T NOVl4r NOVl4s PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCD —ELLHCQNGG- NOVl4 NOVl4u PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCD —ELLHCQNGG- -T NOV14v PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN—ELLHCQNGG- -T

NOVl4a CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD- -SGQGAPPHGSPALLL NOVl b CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD- -SGQGAPPHGSPALLL NOVl4c CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD- -SGQGAPPHGSPALLL NOVl4d NOVl4e CHNNVRCLCPAAYTGILCE KLRCEEAGSCGSD SGQGAPPHGSPALLL NOVl4f CHNNVRCLCPAAYTGILCE KLRCEEAGSCGSD SGQGAPPHGSPALLL NOVl g CSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCV NOVl h CSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCV NOVl4i CSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCV NOVl4j CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD SGQGAPPHGSPALLL NOVl k CNGSGFCECKTGTTGPKCD- -ECLPGNSWHYGCQP NVCDNELLPPCICQDSCR NOVl 1 CHN VRCLCPAAYTGILCE- -KLRCEEAGSCGSD SGQGAPPHGSPALLL NOVl m CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD SGQGAPPHGSPALLL NOVl4 CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD SGQGAPPHGSPALLL NOVl4o CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD SGQGAPPHGSLEKGN NOVl p CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD SGQGAPPHGSPALLL NOVl4q CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD SGQGAPPHGSPALLL NOVl r NOVl4s CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD- -SGQGAPPHGSPALLL NOVl4t NOVl4u CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD- -SGQGAPPHGSPALLL NOVl4 CHNNVRCLCPAAYTGILCE- -KLRCEEAGSCGSD- -SGQGAPPHGSPALLL N0V14a L TTLLGTASPLVF

N0V14b L TTLLGTASPLVF

NOV14c L TTLLGTASPLVFLE

NOV14d

NOV14e L TTLLGTASPLVF

NOV14f L TTLLGTASPLVFLEG

NOV14g SSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAED

NOV14h SSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAED

NOV14i SSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAED

N0V14J L TTLLGTASPLVF

N0V14k F YLWPGRAPARLPREG

N0V141 L TTLLGTASPLVF

N0V14m L TTLLGTASPLVF

N0V14n L TTLLGTASPLVF

N0V14O S TTLD

N0V14p L TTLLGTASPLVF

N0V14q L TTLLGTASPLVF

N0V14r

N0V14S L TTLLGTASPLVF

N0V14t

N0V14U L TTLLGTASPLVF

N0V14v L TTLLGTASPLVF

N0V14a

N0V14b

N0V14c

N0V14d

N0V14e

N0V14f

N0V14g GKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCTEGPIDLVFVID

N0V14h GKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGR

N0V14i GKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCTEGPIDLVFVID

N0V14J

N0V14k

N0V141

N0V14m

N0V14n

NOV14o

N0V14p

N0V14q

N0V14r

N0V14s

N0V14t

N0V14u

N0V14v

N0V14a

N0Vl4b

N0V14c

N0V14d

N0V14e

N0V14f

N0V14g GSKSLGEENFEWKQFVTGIIDSLTISPKAARVGLLQYSTQVHTEFTLRNFNSAKDMKKA

N0V14h

N0V14i GSKSLGEENFEWKQFVTGIIDSLTISPKAARVGLLQYSTQVHTEFTLRNFNSAKDMKKA

N0V14J NOV14k

NOV141

NOV14m

NOV14n

NOV14o

NOV14p

NOV14q

NOV14r

NOV14s

NOV14t

NOV14u

NOV14v

NOV14a

NOV14b

NOV14c

NOV14d

NOV14e

NOV14f

NOVl4g VAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSEWASK

NOV14h

NOVl4i VAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSEWASK

NOV14J

NOV14k

NOV141

NOV14m

NOV14n

NOV14o

NOV14p

NOV14q

NOV14r

NOV14s

NOV14t

NOV14u

NOV14v

NOV14a

NOV14b

NOV14c

NOV14d

NOV14e

NOV14f

NOV14g AKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALEDS

NOV14h -RCKSITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALEDS

NOV14i AKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALEDS

NOVl4

NOV14k

NOV141

NOVl4m

NOV14n

NOV14o

NOV14p

NOV14q

NOV14r

NOV14s

NOV14t

NOVl4u NOVl4j (SEQ ID NO: 180)

NOVl4k (SEQ ID NO: 182)

NOVl41 (SEQ ID NO: 184)

NOVl4m (SEQ ID NO: 186)

NOVl4n (SEQ ID NO: 188)

NOVl4o (SEQ ID NO: 190)

NOV14p (SEQ ID NO: 192)

NOVl4q (SEQ ID NO: 194)

NOVl4r (SEQ ID NO: 196)

NOVl4s (SEQ ID NO: 198)

NOVl4t (SEQ ID NO: 200)

NOVl4u (SEQ ID NO: 204)

NOVl4 (SEQ ID NO: 206)

Further analysis ofthe NOVl4a protein yieldedthe following properties shown in Table 14C.

Table 14C. Protein Sequence Properties NOV14a

SignalP analysis: j Cleavage site betweenresidues 19 and 20

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 5; pos . chg 1; neg.chg 0 H-region: length 25; peak value 8.10 PSG score: 3.70

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.81 possible cleavage site: between 18 and 19

>» Seems to have no N-terminal signal peptide

INTEGRAL Likelihood = -2.87 Transmembrane 464 - 480 PERIPHERAL Likelihood = 3.34 (at 3) ALOM score: -2.87 (number of TMSs: 1)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 471 Charge difference: 0.5 C( 0.0) - N(-0.5) C > N: C-terminal side will be inside

>»Caution: Inconsistent mtop result with signal peptide >» Single TMS is located near the C-terminus

»> membrane topology: type Nt (cytoplasmic tail 1 to 463)

MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75) : 7.91 Hyd Moment(95): 7.87 G content: 1 D/E content: S/T content: Score: -2.60

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 15 SRF | LS

NUCDISC: discrimination of nuclear localization signals pat4: none pat7 : none bipartite: none content of basic residues: 9.6% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals :

XXRR-like motif in the N-terminus: YLSR none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2 : 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: too long tail

Dileucine motif in the tail: found LL at 266 LL at 412 checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs : none

NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 70.6

COIL: Lupas 's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23) :

30.4 %: nuclear

21.7 %: cytoplasmic

13.0 %: Golgi

13.0 %: mitochondrial

8.7 %: endoplas ic reticulum

4.3 %: peroxisomal

4.3 %: plasma membrane

4.3 vesicles of secretory system

» prediction for CG51051-07 is nuc (k=23)

A search of the NOVl 4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14D.

In a BLAST search of public sequence databases, the NOVl 4a protein was found to have homology to the proteins shown in the BLASTP data in Table 14E.

PFam analysis predicts that the NOVl 4a protein contains the domains shown in the Table 14F.

Example 15.

The NOVl 5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15 A.

Table 15A. NOV15 Sequence Analysis

NOVl 5a, CG52261-01 jSEQ ID NO: 211 937 bp DNA Sequence ORF Start: ATG at 317 ORF Stop: TAG at 644 iTCAGTCCTGGTCCCTCCCCTTCTTGGGTTCCTCATCCTGCTCTTCTAAATGTCGAGATGCCTGCAGCA

GTTACGCTTATCTCTGGCCACTATCTCTGCTTTTATCTCCTTTCTTAAAAGTCTTCAATGTCTCTAGG

CTGGTGTGTAAAGTCCTCTATCTTCAGTTACTACACCCTTTTCACCTTCAAAATCCTATGCGCACCTC

AAACTCAGCAAGTGTTAACTGAATTAGTCATCTTTGCTGCCATCGGCTGCCAACCTCCACTGTGGCCT

ACTGTGTGTTTCAAAGATGGCTCCGGAAATTATTCCCGTCCCACATGCTCTTTTGCAACGTGACCCTG

CCATCCCCAATGACAGTGGGAGTCCAATCCTCTCCTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGT CACCAAAAGGATGTGGCAGAAGTGGCACTGTTCAACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCT TTCTCCTGGTTCTACTAGAAGGCTCCCCCCTACAGAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCC AATGGCAGCCCAACGCACAGGAGAGGCTTGCATGTGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTT TCTGGTAACACTTCCCACCTGTCAGATGTGCTAGCGAGGGCACCTCCAGATGACTCCAGTCCTCAGCC AGCTGAGTCACCTGTCATTTGAATTCTTCCAGCTGAGGCTCCCAGACATTGTCAGACAGAGACAAGCC

ATCCACCATCTCTGTGCCCCGTCCAAACTCCTGACCCACGCAGTCCATAAGGAAGAGGTTCTATGCAA

CTAAGTTTGGGATGATGTGTTACACAGCAGTACCCACCACACCCAACAAAACCACCAGTGCTTCCTGG

CTCCCTCTGCCTAAGACATGTGTTTCTGCACATCCATTCACACAGCCAAGAAG

NOV15a, CG52261-01 SEQ ID NO: 212 109 aa MW at 12122.2kD Protein Sequence TFCNVTLPSPMTVGVQSSPLESGIαALRTLVT RM QK HCSTFEARLKRLYSFLLVLLEGSPLQKLA SLKPSSRANGSPTHRRGLHVLQSPAPDEPSFLVTLPTCQMC

NOVl 5b, 268667469 SEQ ID NO: 213 346 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence

CACCGGATCCATGCTCTTTTGCAACGTGACCCTGCCATCCCCAATGACAGTGGGAGTCCAATCCTCTC CTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGTCACCAAAAGGATGTGGCAGAAGTGGCACTGTTCA ACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCTTTCTCCTGGTTCTACTAGAAGGCTCCCCCCTACA GAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCCAATGGCAGCCCAACGCACGGGAGAGGCTTGCATG TGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTTTCTGGTAACACTTCCCACCTGTCAGATGTGCCTC GAGGGC

NOVl 5b, 268667469 SEQ ID NO: 214 115 aa MW at 12567.6kD Protein Sequence

TGSMLFCMVTLPSPMTVGVQSSPLESGLALRTLVT RMWQKWHCSTFEARLKRLYSFLLVLLEGSPLQ KLASL PSSRANGSPTHGRGLHVLQSPAPDEPSFLVTLPTCQMCLEG

NOV15c, CG52261-02 SEQ ID NO: 215 937 bp DNA Sequence ORF Start: ATG at 317 ORF Stop: TAG at 644 iTCAGTCCTGGTCCCTCCCCTTCTTGGGTTCCTCATCCTGCTCTTCTAAATGTCGAGATGCCTGCAGCA

GTTACGCTTATCTCTGGCCACTATCTCTGCTTTTATCTCCTTTCTTAAAAGTCTTCAATGTCTCTAGG

CTGGTGTGTAAAGTCCTCTATCTTCAGTTACTACACCCTTTTCACCTTCAAAATCCTATGCGCACCTC

AAACTCAGCAAGTGTTAACTGAATTAGTCATCTTTGCTGCCATCGGCTGCCAACCTCCACTGTGGCCT

ACTGTGTGTTTCAAAGATGGCTCCGGAAATTATTCCCGTCCCACATGCTCTTTTGCAACGTGACCCTG

CCATCCCCAATGACAGTGGGAGTCCAATCCTCTCCTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGT CACCAAAAGGATGTGGCAGAAGTGGCACTGTTCAACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCT TTCTCCTGGTTCTACTAGAAGGCTCCCCCCTACAGAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCC AATGGCAGCCCAACGCACAGGAGAGGCTTGCATGTGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTT TCTGGTAACACTTCCCACCTGTCAGATGTGCTAGCGAGGGCACCTCCAGATGACTCCAGTCCTCAGCC AGCTGAGTCACCTGTCATTTGAATTCTTCCAGCTGAGGCTCCCAGACATTGTCAGACAGAGACAAGCC ATCCACCATCTCTGTGCCCCGTCCAAACTCCTGACCCACGCAGTCCATAAGGAAGAGGTTCTATGCAA CTAAGTTTGGGATGATGTGTTACACAGCAGTACCCACCACACCCAACAAAACCACCAGTGCTTCCTGG

CTCCCTCTGCCTAAGACATGTGTTTCTGCACATCCATTCACACAGCCAAGAAG

NOV15c, CG52261-02 SEQ ID NO: 216 109 aa MW at 12122.2kD Protein Sequence LFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRM QK HCSTFΞARLKRLYSFLLVLLEGSPLQKLA SLKPSSRANGSPTHRRGLHVLQSPAPDEPSFLVTLPTCQMC

NOV15d, 13382342 SNP for SEQ ID NO: 217 937 bp SNP: 347 C/T

CG52261-01 ORF Start: ATG at ORF Stop: end of sequence

DNA Sequence 317

TCAGTCCTGGTCCCTCCCCTTCTTGGGTTCCTCATCCTGCTCTTCTAAATGTCGAGATGCCTGCAGCAGT TACGCTTATCTCTGGCCACTATCTCTGCTTTTATCTCCTTTCTTAAAAGTCTTCAATGTCTCTAGGCTGG TGTGTAAAGTCCTCTATCTTCAGTTACTACACCCTTTTCACCTTCAAAATCCTATGCGCACCTCAAACTC AGCAAGTGTTAACTGAATTAGTCATCTTTGCTGCCATCGGCTGCCAACCTCCACTGTGGCCTACTGTGTG TTTCAAAGATGGCTCCGGAAATTATTCCCGTCCCACATGCTCTTTTGCAACGTGACCCTGCCATCC CAA TGACAGTGGGAGTCCAATCCTCTCCTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGTCACCAAAAGGAT GTGGCAGAAGTGGCACTGTTCAACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCTTTCTCCTGGTTCTA CTAGAAGGCTCCCCCCTACAGAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCCAATGGCAGCCCAACGC ACAGGAGAGGCTTGCATGTGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTTTCTGGTAACACTTCCCAC CTGTCAGATGTGCTAGCGAGGGCACCTCCAGATGACTCCAGTCCTCAGCCAGCTGAGTCACCTGTCATTT GAATTCTTCCAGCTGAGGCTCCCAGACATTGTCAGACAGAGACAAGCCATCCACCATCTCTGTGCCCCGT CCAAACTCCTGACCCACGCAGTCCATAAGGAAGAGGTTCTATGCAACTAAGTTTGGGATGATGTGTTACA CAGCAGTACCCACCACACCCAACAAAACCACCAGTGCTTCCTGGCTCCCTCTGCCTAAGACATGTGTTTC TGCACATCCATTCACACAGCCAAGAAG

NOV15d, 13382342 SNP for SEQ ID NO: 109 aa SNP: Pro to Ser at position

CG522 1-01 218 11

Protein Sequence

MLFCNVTLPSSMTVGVQSSPLESGLALRTLVTKRM QK HCSTFEARL RLYSFLLVLLEGSPLQKLASL KPSSRANGSPTHRRGLHVLQSPAPDEPSFLVTLPTCQMC

NOV15e, 13382341 SNP for SEQ ID NO: 219 [937 bp SNP: 563 A/G

CG52261-01 ORF Start: ATG at ORF Stop: end of sequence

DNA Sequence 317

TCAGTCCTGGTCCCTCCCCTTCTTGGGTTCCTCATCCTGCTCTTCTAAATGTCGAGATGCCTGCAGCAGT TACGCTTATCTCTGGCCACTATCTCTGCTTTTATCTCCTTTCTTAAAAGTCTTCAATGTCTCTAGGCTGG TGTGTAAAGTCCTCTATCTTCAGTTACTACACCCTTTTCACCTTCAAAATCCTATGCGCACCTCAAACTC AGCAAGTGTTAACTGAATTAGTCATCTTTGCTGCCATCGGCTGCCAACCTCCACTGTGGCCTACTGTGTG TTTCAAAGATGGCTCCGGAAATTATTCCCGTCCCACATGCTCTTTTGCAACGTGACCCTGCCATCCCCAA TGACAGTGGGAGTCCAATCCTCTCCTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGTCACCAAAAGGAT GTGGCAGAAGTGGCACTGTTCAACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCTTTCTCCTGGTTCTA CTAGAAGGCTCCCCCCTACAGAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCCAATGGCAGCCCAACGC ACGGGAGAGGCTTGCATGTGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTTTCTGGTAACACTTCCCAC CTGTCAGATGTGCTAGCGAGGGCACCTCCAGATGACTCCAGTCCTCAGCCAGCTGAGTCACCTGTCATTT GAATTCTTCCAGCTGAGGCTCCCAGACATTGTCAGACAGAGACAAGCCATCCACCATCTCTGTGCCCCGT CCAAACTCCTGACCCACGCAGTCCATAAGGAAGAGGTTCTATGCAACTAAGTTTGGGATGATGTGTTACA CAGCAGTACCCACCACACCCAACAAAACCACCAGTGCTTCCTGGCTCCCTCTGCCTAAGACATGTGTTTC TGCACATCCATTCACACAGCCAAGAAG

NOV15e, 13382341 SNP for iSEQ ID NO: 109 aa SNP: Arg to Gly at position 83 CG52261-01 J220

Protein Sequence

MLFCNVTLPSPMTVGVQSSPLESGIjALRTLVTKRMWQ HCSTFEARLKRLYSFLLVLLEGSPLQKLASL KPS SRANGS PTHGRGLHVLQS PAPDEPS FLVTLPTCQMC A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 15B.

Table 15B. Comparison of the NOV15 protein sequences.

NOV15a MLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRM QKWHCSTFEARLKRLYSFLLV

NOV15b TGSMLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRM QK HCSTFEARLKRLYSFLLV

NOV15c MLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRMWQK HCSTFEARLKRLYSFLLV

NOV15a LLEGSPLQKLASLKPSSRANGSPTHRRGLHVLQSPAPDEPSFLVTLPTCQMC

NOV15b LLEGSPLQKLASLKPSSRANGSPTHGRGLHVLQSPAPDEPSFLVTLPTCQMCLEG

NOV15C LLEGSPLQKLASLKPSSRAGSPTHRRGLHVLQSPAPDEPSFLVTLPTCMC

NOV15a (SEQ ID NO: 212)

NOV15b (SEQ ID NO: 214)

NOV15c (SEQ ID NO: 216)

Further analysis oftheNOVl5aprotein yieldedthe following properties shown in Table 15C.

Table 15C. Protein Sequence Properties NOV15a

SignalP analysis: Cleavage site betweenresidues 65 and 66

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 0; pos.chg 0; neg.chg 0 H-region: length 21; peak value 7.16 PSG score: 2.76

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.57 possible cleavage site: between 18 and 19

>» Seems to have no N-terminal signal peptide

Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 3.18 (at 54) ALOM score: 3.18 (number of TMSs: 0)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 6 Charge difference: 1.0 C( 2.0) - N( 1.0) C > N: C-terminal side will be inside

>»Cau ion: Inconsistent mtop result with signal peptide MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 5.42 Hyd Moment (95) : 2.82 G content: 1 D/E content: 1 S/T content: 5 Score: -4.44

Gavel: prediction of cleavage sites for mitochondrial preseq R-3 motif at 53 KRLY1S

NUCDISC: discrimination of nuclear localization signals pat : none pat7 : none bipartite: none content of basic residues: 11.0% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals : none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2 : 2nd peroxisomal targeting signal : none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1: none type 2: none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23) :

65.2 %: nuclear

21.7 %: mitochondrial

8.7 % : cytoplasmic

4.3 % : peroxisomal | » prediction for CG52261-01 is nuc ( k=23 )

A search of the NOVl 5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15D.

In a BLAST search of public sequence databases, the NOVl 5a protein was found to have homology to the proteins shown in the BLASTP data in Table 15E.

Example 16.

The NOVl 6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16 A.

Table 16A. NOV16 Sequence Analysis

NOVl 6a, CG52414-02 SEQ ID NO: 221 3040 bp DNA Sequence ORF Start: ATG at 338 ORF Stop: TGA at 2819

TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAG

GCCAGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGG

CAGGTGGAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCAC

AGACTGAGGCTTGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACATGCTCTAAAGCCCT iTCACAGCAAGACCCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAATG

GCCTCTGCTGACAAGAATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCC ACCCAACCTCTCCATCACCATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCA TGCTGCCTGAGAGGAAGAACCCAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGG CAGGAGAGTTCAGAGAAGCGCCCTGGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGG CGCAGCCCAGTGGTTTGGAGTCAGCGGCGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCC TGCACCACTGCAGCATGCGCTACGGCCGCCTGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGC CAGGAGGCACCGTCCTTCCAGGGCACTGAGTCCCCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCC GCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGAGATGGACAGGCCCCACGCCCCGCACCCACCGC TGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTGTCCGTTCTGGCTACTCCCACCTGCCACGC CGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCCGCTGCCCTCCTCAAGGGGCGCTCGGT GCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTTTGCCTTCCCGAGCTTCCTGGAGG AGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTAAGGAAGAAATGAGCTCCATG CCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGGATCCCACACTCAGCCTC CCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCCAGTCCCCGGGCCCC GGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGCGGCACTACGGC CTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTGCAGCGGCA GCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCATCATCA CGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGCTG GTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCC CAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCG AGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCC GGATGCATCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGA CACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGG ACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGG CCGATCTGCACAGAGCAGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGG CCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGC ACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTG CTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGC TGGGGTGGTGCACTGCCTCGTGTCTGTGGTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGG CCGGCTGGCACCGTATCGCCATCATCTTCATCCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATC TTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCGGCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGT GGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCCTGGAAGGCCTTCCTCAACCTCTCGGCCATCG TGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGACAACATCGCCCACATCTTCGGCTTCCTC AGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCTTCGGCACCAGCGACAAGTACCGCAA GCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTCGCCGCCCTCGTGCTGTGGCTGT ACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCCCTTCACCAGCCGCTTCTGC GAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTGCCCCTCAGCCCTGCTG GAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGAGAGCCAGAGACCC

AAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGCGTGAGATAGA

TGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAAA

NOV16a, CG52414-02 SEQ ID NO: 222 827 aa MW at 93378.2kD Protein Sequence

MASADKNGGSVSSVSSSRLQSR PPNLSITIPPPE ETQAPGEQDSMLPERKNPAYLKSVSLQEPRSR QESSΞKRPGFRRQASLSQSIRKGAAQ FGVSGDWEGQRQQ QRRSLHHCSMRYGRLKASCQRDLELP SQEAPSFQGTESPKPCKMP IVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLP RR RMSVAHMSLQAAAALLKGRSVLDATGQRCRWKRSFAFPSFLEEDWDGADTFDSSFFS EEMSS MPDDVFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRK RHY GLGWGNWLNRSYRRSISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQ LVLRNKGVYESVKYIQQENF VGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQNDH SGCIQTQRKDCSETLATFV WQDDTGPPMDKSDLGQ RTSGAVCHQDPRTCEEPASSGAHI PDDITK PICTEQARSNRTGFLHMDCEIKGRPCCIGT GSCEITTREYCEFiVIHGYFHEEATLCSQVHCLD VCG LLPFLNPΞVPDQFYRL LSLFLHAGWHCLVSWFQMTILRDLEKLAGWHRIAIIFILSGITGNLASA IFLPYRAEVGPAGSQFGLLACLFVELFQSWPLLERP KAFLNLSAIVLFLFICGLLP IDNIAHIFGF LSGLLLAFAFLPYITFGTSDKYRKRALILVSLLAFAGLFAALVLWLYIYPIN P IEHLTCFPFTSRF CEKYELDQVLH

NOV16b, 305262879 SEQ ID NO: 223 694 bp DNA Sequence ORF Start: at 2 [ORF Stop: end of sequence

CACCAGATCTCAGCACGTCACCACCCAGCTGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGT ACATCCAGCAGGAGAACTTCTGGGTTGGCCCCAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTC TCACCCTGCATCCGGAAGGACGGGCAGATCGAGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGA CTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCATCCAGACCCAGCGGAAGGACTGCTCGGAGA CTTTGGCCACTTTTGTCAAGTGGCAGGATGACACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAG AAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGC CCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGCAGGCCAGGAGCAACCACACAG GCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAG ATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCA GGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCT ACAGGCTCGAGGGC

NOVl 6b, 305262879 SEQ ID NO: 224 231 aa MW at 26183.3kD Protein Sequence

TRSQHVTTQLVLRN GVYESVKYIQQENF VGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERD SGCCVQNDHSGCIQTQR DCSETLATFVK QDDTGPPMD SDLGQKRTSGAVCHQDPRTCEEPASSGA HIWPDDITK PICTEQARSNHTGFLH DCEIKGRPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQ VHCLDKVCGLLPFLNPEVPDQFYRLEG

NOV16c, 319073326 SEQ ID NO: 225 2506 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence

CACCAGATCTCCCACCATGGCCTCTGCTGACAAGAATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCC GCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCACCATCCCGCCACCCGAGAAAGAGACCCAGGCC CCTGGCGAGCAAGACAGCATGCTGCCTGAGAGGAAGAACCCAGCCTACTTGAAGAGCGTCAGCCTCCA GGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCTGGCTTCCGCCGCCAGGCCTCACTGT CCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGGCGACTGGGAGGGGCAGCGGCAG CAGTGGCAGCGCCGCAGCCCGCACCACTGCAGCATGCGCTACGGCCGCCTGAAGGCCTCGTGCCAGCG TGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCCCCAAAGCCCTGCAAGA TGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGAGATGGACAGGCCC CACGCCCTGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTGTCCGTTCTGG CTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCCGCTGCCC TCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGATGGTCAAGCGCAGCTTTGCC TTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTAA GGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAG GGATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGA GCCCCAGTCCCCGGGCCCCGGCGCGGTGAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCG GAAGAAGCGGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGTTACCGCCGCAGCATCA GCAGCACTGTGCAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACC TTCGTCCATGTCATCATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCA GCACGTCACCACCCAGCTGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGG AGAACTTCTGGGTTGGCCCCAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATC CGGAAGGACGGGCAGATCGAGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTG TGTCCAGAATGACCACTCCGGATGCATCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTT TTGTCAAGTGGCAGGATGACACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCG GGGGCTGTCTGCCACCAGGACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCC CGATGACATCACTAAGTGGCCGATCTGCACAGAGCAGGCCAGGAGCAACCACACAGGCTTCCTGCACA TGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAGATCACCACCCGG GAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCAGGTGCACTGCTT GGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCTACAGGCTCTGGC TGTCTCTCTTCCTACATGCTGGCGTGGTGCACTGCCTCGTGTCTGTGGTCTTTCAAATGACCATCCTG AGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCATCCTCAGTGGCATCACAGG CAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTGGGCCCGGCCGGCTCACAGTTCGGCC TCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCCTGGAAGGCCTTC CTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGACAACATCGC CCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCTTCGGCA CCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTCGCC GCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACCTCGAGGGC

NOV16c, 319073326 SEQ ID NO: 226 835 aa MW at 94253. lkD Protein Sequence

TRSPTMASAD NGGSVSSVSSSRLQSR PPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQ EPRSRWQESSEKRPGFRRQASLSQSIRKGAAQWFGVSGD EGQRQQ QRRSPHHCSMRYGRL ASCQR DLELPSQEAPSFQGTESPKPCKMP IVDPLARGRAFRHPEEMDRPHALHPPLTPGVLSLTSFTSVRSG YSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQRCRMVKRSFAFPSFLEEDWDGADTFDSSFFSK EEMSSMPDDVFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGERIASKVKHFAFDR KKROTGLG GNWLNRSYRRSISSTVQRQLΞSFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQ HVTTQLVLRNKGVYESVKYIQQENF VGPSSIDLIHLGA FSPCIRKDGQIEQLVLRERDLERDSGCC VQNDHSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGAHIWP DDITK PICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCL DKVCGLLPFLNPEVPDQFYRLWLSLFLHAGWHCLVSWFQMTILRDLEKLAGWHRIAIIFILSGITG NLASAIFLPYRAEVGPAGSQFGLLACLFVELFQS PLLERP AFLNLSAIVLFLFICGLLPWIDNIA HIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLLAFAGLFAALVLWLYIYPINWP IEHLTCFP FTSRFCEKYELDQVLHLEG

NOV16d, CG52414-01 SEQ ID NO: 227 2596 bp DNA Sequence ORF Start: ATG at 289 ORF Stop: TGA at 2413

TCAATTGACTTGATATGATTTATTATTTTTACTACTTATAAGAATGGAAATAAGTTCTCCTTAGTTTT

TTTCTTGGAGAAAGTCTGACATGTGAGGCACAGATGAGTTATTAAAGGCAGATGACTTTCCAGCCTTG

TCTTAAATGTTCCATTCTTTACCTTAGAAATTATTTAAATTTGTGTCCTGTCCCAGAGCATCCGCAAG

GGCGCAGCCCAGTGGTTTGGAGTCAGCGGCGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAG

CCTGCACCACTGCAGCATGCGCTACGGCCGCCTGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCA

GCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCCCCAAAGCCCTGCAAGATGCCCAAGATTGTGGAT CCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGAGATGGACAGGCCCCACGCCCTGCACCCACC GCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTGTCCGTTCTGGCTACTCCCACCTGCCAC GCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCCGCTGCCCTCCTCAAGGGGCGCTCG GTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTTTGCCTTCCCGAGCTTCCTGGA GGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTAAGGAAGAAATGAGCTCCA TGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGGATCCCACACTCAGCC iTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCCAGTCCCCGGGCC CCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGCGGCACTACG GCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTGCAGCGG CAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCATCAT CACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGC TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGC CCCAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGOAAGGACGGGCAGAT CGAGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACT CCGGCTGCATCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGAT GACACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCA GGACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGT GGCCGATCTGCACAGAGCAGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAG GGCCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCAT GCACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGC TGCTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACAT GCTGGCGTGGTGCACTGCCTCGTGTCTGTGGTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCT GGCCGGCTGGCACCGTATCGCCATCATCTTCATCCTCAGTGGCATCACAGGCAACCTCGCCAGTACCA TCTTTCTCCCATACCGGGCAGAGGTGGGCCCGGCCGGCTCACAGTTCGGCCTCCTCGCCTGCCTCTTC GTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCCTGGAAGGCCTTCCTCAACCTCTCGACCAT CGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGACAACATCGCCCACATCTTCGGCTTCC TCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCTTCGGCACCAGCGACAAGTACCGC AAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTCGCCGCCCTCGTGCTGTGGCT GTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCCCTTCACCAGCCGCTTCT GCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTGCCCCTCAGCCCTGC TGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGAGAGCCAGAGAC

CCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGCGTGAGATG

GTTGGTTAAGGC

NOV16d, CG52414-01 SEQ ID NO: 228 708 aa MW at 80098.6kD Protein Sequence

MRYGRLKASCQRDLELPSQEAPSFQGTESP PC MPKIVDPLARGRAFRHPEE DRPHALHPPLTPGV LSLTSFTSVRSGYSHLPRRKR SVAHMSLQAAAALLKGRSVLDATGQRCRWKRSFAFPSFLEEDWD GADTFDSSFFSKEEMSS PDDVFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKR IAS V HFAFDRK RHYGLGVVGNWLNRSYRRSISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVI CTYGIAPVGFAQHVTTQLVLRNKGVYESVKYIQQENF VGPSSIDLIHLGAKFSPCIRKDGQIEQLVL RERDLERDSGCCVQNDHSGCIQTQRKDCSETLATFVKWQDDTGPPrøKSDLGQl TSGAVCHQDPRTC EEPASSGAHI PDDITKWPICTEQARSNHTGFLH DCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH EΞATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLHAGWHCLVSWFQMTILRDLEKLAG HR IAIIFILSGITGNLASTIFLPYRAEVGPAGSQFGLLACLFVELFQS PLLERP AFLNLSTIVLFLF ICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLLAFAGLFAALVLWLYIYPI NWPWIEHLTCFPFTSRFCEKYELDQVLH

NOV16e, CG52414-03 SEQ ID NO: 229 2516 bp DNA Sequence ORF Start: ATG at 17 ORF Stop: end of sequence

CACCAGATCTCCCACCATGGCCTCTGCTGACAAGAATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCC

GCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCACCATCCCGCCACCCGAGAAAGAGACCCAGGCC CCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACCCAGCCTACTTGAAGAGCGTCAGCCTCCA GGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCTGGCTTCCGCCGCCAGGCCTCACTGT CCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGGCGACTGGGAGGGGCAGCGGCAG CAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCCTGAAGGCCTCGTGCCAGCG TGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCCCCAAAGCCCTGCAAGA TGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGAGATGGACAGGCCC CACGCCCCGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTGTCCGTTCTGG CTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCCGCTGCCC TCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTTTGCC iTTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTAA GGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAG GGATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGA GCCCCAGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCG GAAGAAGCGGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCA GCAGCACTGTGCAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACC TTCGTCCATGTCATCATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCA GCACGTCACCACCCAGCTGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGG AGAACTTCTGGGTTGGCCCCAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATC CGGAAGGACGGGCAGATCGAGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTG TGTCCAGAATGACCACTCCGGATGCATCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTT TTGTCAAGTGGCAGGATGACACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCG GGGGCTGTCTGCCACCAGGACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCC CGATGACATCACTAAGTGGCCGATCTGCACAGAGCAGGCCAGGAGCAACCACACAGGCTTCCTGCACA TGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAGATCACCACCCGG GAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCAGGTGCACTGCTT GGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCTACAGGCTCTGGC TGTCTCTCTTCCTACATGCTGGCGTGGTGCACTGCCTCGTGTCTGTGGTCTTTCAAATGACCATCCTG AGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCATCCTCAGTGGCATCACAGG CAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTGGGCCCGGCCGGCTCACAGTTCGGCC TCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCCTGGAAGGCCTTC CTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGACAACATCGC CCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCTTCGGCA CCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTCGCC GCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCAC

NOV16e, CG52414-03 SEQ ID NO: 230 827 aa MW at 93378.2kD

Protein Sequence 1

MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQEPRSR QESSEKRPGFRRQASLSQSIRKGAAQWFGVSGD EGQRQQ QRRSLHHCS RYGRLKASCQRDLELP SQEAPSFQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLP RRKEMSVAHMSLQAAAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSS MPDDVFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHY GLGWGN LNRSYRRSISSTVQRQLESFDSHRPYFTY LTFVHVIITLLVICTYGIAPVGFAQHVTTQ LVLRNKGVYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQNDH SGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCΞEPASSGAHIWPDDITK PICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCG LLPFLNPEVPDQFYRLWLSLFLHAGWHCLVSWFQMTILRDLE LAG HRIAIIFILSGITGNLASA IFLPYRAEVGPAGSQFGLLACLFVELFQS PLLERP KAFLNLSAIVLFLFICGLLP IDNIAHIFGF LSGLLLAFAFLPYITFGTSD YRKRALILVSLLAFAGLFAALVLWLYIYPIN P IEHLTCFPFTSRF CEKYELDQVLH

NOVlβf, 13379509 SNP for SEQ ID NO: 231 3040 bp SNP: 873 C/T

CG52414-02 ORF Start: ATG at ORF Stop: TGA at 2819

DNA Sequence 338

TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAGGCC

AGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGGCAGGTG

GAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCACAGACTGAGG

CTTGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACATGCTCTAAAGCCCTTCACAGCAAGAC

CCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAATGGCCTCTGCTGACAAG

AATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCAC CATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACC CAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCT GGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGG CGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCC TGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCC CCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGA GATGGACAGGCCCCACGCCCTGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTG TCCGTTCTGGCTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCC GCTGCCCTCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTT TGCCTTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTA AGGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGG ATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCC AGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGC GGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTG CAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCAT CATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGG TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCCC AGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCGAGCA GCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCA TCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGACACTGGGCCC CCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTG CGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGC AGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGC ACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGC AACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCC CAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGCTGGGGTGGTGCACTGCCTCGTGTCTGTG GTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCAT CCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCG GCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCC TGGAAGGCCTTCCTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGA CAACATCGCCCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCT TCGGCACCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTC GCCGCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTG

CCCCTCAGCCCTGCTGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGA

GAGCCAGAGACCCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGC

GTGAGATAGATGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAAA

NOVlθf, 13379509 SNP for SEQ ID NO: 827 aa SNP: Pro to Leu at position 179

CG52414-02 232

Protein Sequence

MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPE ETQAPGEQDSMLPERKNPAYLKSVSLQEPRSR QE SSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQ QRRSLHHCSMRYGRLKASCQRDLELPSQEAPS FQGTESPKPCKMP IVDPLARGRAFRHPEEMDRPHALHPPLTPGVLSLTSFTSVRSGYSHLPRRKR SVAH MSLQAAAALLKGRSVLDATGQRCRWKRSFAFPSFLEEDWDGADTFDSSFFSKEEMSSMPDDVFESPPLS AS FRGIPHSASPVSPDGVQIPLI03YGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGVVGNWLNRSYRR SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRN GVYESVKYIQQE NF VGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQNDHSGCIQTQRKDCSETLATFVK QDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGAHI PDDITK PICTEQARSNHTGFLHMDCEIKG RPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRL LSLFLHAGW HCLVSWFQMTILRDLEKLAG HRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQSW PLLERP KAFLNLSAIVLFLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLL AFAGLFAALVL LYIYPIN P IEHLTCFPFTSRFCEKYELDQVLH

NOV16g, 13381817 SNP for SEQ ID NO: 233 j3040 bp SNP: 971 G/A

CG52414-02 ORF Start: ATG at 338 ORF Stop: TGA at 2819

DNA Sequence

TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAGGCC AGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGGCAGGTG GAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCACAGACTGAGG

CTTGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACATGCTCTAAAGCCCTTCACAGCAAGAC CCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAATGGCCTCTGCTGACAAG AATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCAC CATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACC CAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCT GGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGG CGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCC TGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCC CCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGA GATGGACAGGCCCCACGCCCCGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTG TCCGTTCTGGCTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGACCCACATGAGCTTGCAAGCTGCC GCTGCCCTCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTT TGCCTTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTA AGGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGG ATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCC AGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGC GGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTG CAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCAT CATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGC TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCCC AGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCGAGCA GCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCA TCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGACACTGGGCCC CCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTG CGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGC AGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGC ACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGC AACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCC CAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGCTGGGGTGGTGCACTGCCTCGTGTCTGTG GTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCAT CCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCG GCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCC TGGAAGGCCTTCCTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGA CAACATCGCCCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCT TCGGCACCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTC GCCGCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTG

CCCCTCAGCCCTGCTGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGA iGAGCCAGAGACCCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGC

GTGAGATAGATGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAAA

NOV16g,13381817 SNP for SEQ ID NO: 827 aa ι SNP: Ala to Thr at position

CG52414-02 234 212

Protein Sequence ASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQEPRSRWQE SSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSLHHCSMRYGRLKASCQRDLELPSQEAPS FQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVTH MSLQAAAALLKGRSVLDATGQRCRWKRSFAFPSFLEEDWDGADTFDSSFFSKEEMSSMPDDVFESPPLS ASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGFJIIASKVKHFAFDRKKRHYGLGVVGNWLNRSYRR SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKGVYESVKYIQQE NFWVGPSSIDLIHLGA FSPCIRKDGQIEQLVLRERDLERDSGCCVQNDHSGCIQTQRKDCSETLATFVK QDDTGPP DKSDLGQKRTSGAVCHQDPRTCEEPASSGAHI PDDITK PICTEQARSNHTGFLHMDCEIKG RPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRL LSLFLHAGW HCLVSWFQMTILRDLEKLAGWHRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQS PLLERPWKAFLNLSAIVLFLFICGLLP IDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLL AFAGLFAALVLWLYIYPINWP IEHLTCFPFTSRFCEKYELDQVLH iNOV16h, 13382069 SNP for SEQ ID NO: 235 3040 bp SNP: 1247 C/T

CG52414-02 ORF Start: ATG at 338 ORF Stop: TAA at 1247 DNA Sequence

TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAGGCC AGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGGCAGGTG

GAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCACAGACTGAGG

CTTGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACATGCTCTAAAGCCCTTCACAGCAAGAC

CCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAATGGCCTCTGCTGACAAG

AATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCAC CATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACC CAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCC GGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGG CGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCC TGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCC CCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGA GATGGACAGGCCCCACGCCCCGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTG TCCGTTCTGGCTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCC GCTGCCCTCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTT TGCCTTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTA AGGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGG ATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGTAAATCCCTCTGAAGGAGTATGGCCGAGCCCC

AGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGC

GGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTG

CAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCAT

CATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGC

TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCCC

AGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCGAGCA

GCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCA

TCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGACACTGGGCCC

CCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTG

CGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGC

AGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGC

ACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGC

AACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCC

CAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGCTGGGGTGGTGCACTGCCTCGTGTCTGTG

GTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCAT

CCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCG jGCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCC

TGGAAGGCCTTCCTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGA

CAACATCGCCCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCT

TCGGCACCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTC

GCCGCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC

CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTG

CCCCTCAGCCCTGCTGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGA

GAGCCAGAGACCCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGC

GTGAGATAGATGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAAA

NOV16h, 13382069 SNP for SEQ ID NO: 827 aa SNP: Gin to STOP at position CG52414-02 1236 304

Protein Sequence

MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQEPRSR QE SSEKRPGFRRQASLSQSIRKGAAQ FGVSGDWEGQRQQ QRRSLHHCS RYGRLKASCQRDLELPSQΞAPS FQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAH MSLQAAAALL GRSVLDATGQRCRWKRSFAFPSFLEEDWDGADTFDSSFFSKEEMSSMPDDVFESPPLS ASYFRGIPHSASPVSPDGV*

NOV16i, 13381560 SNP for SEQ ID NO: 237 J3040 bp SNP: 2493 C/T

CG52414-02 ORF Start: ATG at 338 ORF Stop: TGA at 2819

DNA Sequence

TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAGGCC AGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGGCAGGTG GAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCACAGACTGAGG CTTGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACATGCTCTAAAGCCCTTCACAGCAAGAC

CCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAAXGGCCTCTGCTGACAAG

AATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCAC CATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACC CAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCT GGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGG CGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCC TGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCC CCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGA GATGGACAGGCCCCACGCCCCGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTG TCCGTTCTGGCTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCC GCTGCCCTCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTT TGCCTTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTA AGGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGG ATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCC AGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGC GGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTG CAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCAT CATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGC TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCCC AGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCGAGCA GCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCA TCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGACACTGGGCCC CCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTG CGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGC AGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGC ACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGC AACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCC CAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGCTGGGGTGGTGCACTGCCTCGTGTCTGTG GTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCAT CCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCG GCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCC TGGAAGGTCTTCCTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGA CAACATCGCCCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCT TCGGCACCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTC GCCGCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTG

CCCCTCAGCCCTGCTGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGA

GAGCCAGAGACCCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGC

GTGAGATAGATGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAAA

NOV16i, 13381560 SNP for _* SEQ ID NO: 827 aa JSNP: Ala to Val at position 719 CG52414-02 238

Protein Sequence

MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQEPRSRWQE SSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSLHHCSMRYGRLKASCQRDLELPSQEAPS FQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAH SLQAAAALL GRSVLDATGQRCRW RSFAFPSFLEEDWDGADTFDSSFFSKEEMSSMPDDVFESPPLS ASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGWGNWLNRSYRR SISSTVQRQLESFDSHRPYFTY LTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKGVYESVKYIQQE NF VGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQNDHSGCIQTQRKDCSETLATFVKW QDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGAHI PDDITKWPICTEQARSNHTGFLHMDCEIKG RPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRL LSLFLHAGW HCLVSWFQMTILRDLEKLAGWHRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVΞLFQS PLLERP KVFLNLSAIVLFLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLL AFAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRFCEKYELDQVLH A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 16B.

Table 16B. Comparison of the NOV16 protein sequences.

NOVl6a MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPA

NOV16b

NOVl6c TRSPTMASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPE ETQAPGEQDSMLPER NPA

NOV16d

NOV16e MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPA

NOVl6a YLKSVSLQEPRSR QESSEKRPGFRRQASLSQSIRKGAAQWFGVSGD EGQRQQWQRRSL

NOVl6b

NOVl6c YLKSVSLQEPRSR QESSEKRPGFRRQASLSQSIRKGAAQ FGVSGD EGQRQQ QRRSP

NOV16d

NOV16e YLKSVSLQEPRSRWQESSEKRPGFRRQASLSQSIRKGAAQ FGVSGD EGQRQQ QRRSL

NOV16a HHCSMRYGRLKASCQRDLELPSQEAPSFQGTESPKPCK PKIVDPLARGRAFRHPEEMDR

NOVl6b

NOVl6c HHCSMRYGRLKASCQRDLELPSQEAPSFQGTESPKPCKMPKIVDPLARGRAFRHPEEMDR

NOV16d MRYGRLKASCQRDLELPSQEAPSFQGTESPKPCK PKIVDPLARGRAFRHPEEMDR

NOV16e HHCSMRYGRLKASCQRDLELPSQEAPSFQGTESPKPCK PKIVDPLARGRAFRHPEEMDR

NOVl6a PHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQR NOVl6b NOVl6c PHALHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQR NOV16d PHALHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQR NOV16e PHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQR

NOVl6a CRWKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLSASYFRGIPHSA NOVl6b NOVl6c CRMVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLSASYFRGIPHSA NOVl6d CRWKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLSASYFRGIPHSA NOVl6e CRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLSASYFRGIPHSA

NOVl6a SPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGWGNWLNRSYRR NOVl6b NOVl6c SPVSPDGVQIPLKEYGRAPVPGPRRGERIASKVKHFAFDRKKRHYGLGVVGN LNRSYRR NOV16d SPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGWGN LNRSYRR NOV16e SPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGVVGN LNRSYRR

NOVl6a SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKG NOVl6b TRS_QH_VTT_QLVLR_NKG NOVl6c SISSTVQRQLESFDSHRPYFTY LTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKG NOV16d SISSTVQRQLESFDSHRPYFTY LTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKG NOV16e SISSTVQRQLESFDSHRPYFTY LTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRN G

NOVl6a VYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND NOVl6b VYESVKYIQQENFVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND NOVl6c VYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND NOV16d VYESVKYIQQENFVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND NOVlδe VYESVKYIQQENF VGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND

NOVl6a HSGCIQTQRKDCSETLATFVK QDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA NOVl6b HSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA NOVl6c HSGCIQTQRKDCSETLATFVK QDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA NOV16d HSGCIQTQRKDCSETLATFVKQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA

NOVlδe HSGCIQTQRKDCSETLATFVK QDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA

NOV16a HIWPDDITK PICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH

NOVl6b HIWPDDITK PICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH

NOV16c HIWPDDITKWPICTEQARSNHTGFLH DCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH

NOV16d HI PDDITK PICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH

NOV16e HIWPDDITKWPICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH

NOV16a EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRL LSLFLHAGWHCLVSWFQMTILRDL

NOVl6b EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLEG

NOV16C EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLHAGWHCLVSVVFQMTILRDL

NOV16d EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRL LSLFLHAGWHCLVSVVFQMTILRDL

NOVlδe EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRL LSLFLHAGWHCLVSVVFQMTILRDL

NOVl6a EKLAG HRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQS PLLER NOVl6b NOVl6c EKLAGWHRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQS PLLER NOVlδd EKLAG HRIAIIFILSGITGNLASTIFLPYRAEVGPAGSQFGLLACLFVELFQS PLLER NOV16e EKLAG HRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQS PLLER

NOVl6a P KAFLNLSAIVLFLFICGLLP IDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRAL NOVl6b NOVl6c P KAFLNLSAIVLFLFICGLLP IDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRAL NOVlβd P KAFLNLSTIVLFLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRAL NOV16e P KAFLNLSAIVLFLFICGLLP IDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRAL

NOVl6a ILVSLLAFAGLFAALVL LYIYPIN P IEHLTCFPFTSRFCEKYELDQVLH NOVl6b NOVl6c ILVSLLAFAGLFAALVL LYIYPINWP IEHLTCFPFTSRFCEKYELDQVLHLEG NOV16d ILVSLLAFAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRFCEKYELDQVLH NOV16e ILVSLLAFAGLFAALVL LYIYPIN PWIEHLTCFPFTSRFCEKYELDQVLH

NOVl6a (SEQ ID NO 222)

NOVl6b (SEQ ID NO 224)

NOVl6c (SEQ ID NO 226)

NOV16d (SEQ ID NO 228)

NOV16e (SEQ ID NO 230)

Further analysis of the NOVl 6a protein yielded the following properties shown in Table 16C.

Table 16C. Protein Sequence Properties NOVlόa

SignalP analysis: No Known Signal Sequence Predicted

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 6; pos.chg 1; neg.chg 1 H-region: length 11; peak value 5.03 PSG score: 0.62

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -7.64 possible cleavage site : between 21 and 22 >» Seems to have no N-terminal signal peptide

ALOM: Klein et al's method for TM region allocation

Init position for calculation: 1

Tentative number of TMS(s) for the threshold 0. 5: 7

INTEGRAL Likelihood = -6. .42 Transmembrane 381 - 397

INTEGRAL Likelihood = -4. .25 Transmembrane 630 - 646

INTEGRAL Likelihood = -3, .08 Transmembrane 666 - 682

INTEGRAL Likelihood = 0, .37 Transmembrane 697 - 713

INTEGRAL Likelihood = -9. .08 Transmembrane 720 - 736

INTEGRAL Likelihood = -4. .83 Transmembrane 742 - 758

INTEGRAL L Liikkeelliihhoooodd ==--1100...8833 Transmembrane 775 - 791

PERIPHERAL LLiikkeelliihhoooodd == 55...2255 (at 600)

ALOM score: -10.83 (number of TMSs: 7)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 388 Charge difference: 0.5 C( 1.5) - N( 1.0) C > N: C-terminal side will be inside

>»Caution: Inconsistent mtop result with signal peptide »> membrane topology: type 3b

MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 6.30 Hyd Moment (95): 5.24 G content: 2 D/E content: 2 S/T content: 10 Score: -3.23

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 32 SRK|PP

NUCDISC: discrimination of nuclear localization signals pat4: PRRK (4) at 204 pat4: RRKR (5) at 205 pat4: RKKR (5) at 335 pat4: KKRH (3) at 336 pat7: PRRKRMS (5) at 204 pat7: PGPRRGK (3) at 316 pat7: PRRGKRI (5) at 318 bipartite: KRIASKVKHFAFDRKKR at 322 content of basic residues: 11.6% NLS Score: 2.37

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals : none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23)

55 6 9- - erxdoplasiriic reticulurα

11 1 9 o- « _• vacuolar

11 1 9- - mitochondrial

11 1 vesicles of secretory system

11 1 9- - Golgi

» prediction for CG52414-02 is end (k=9)

A search of the NOVl 6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16D.

In a BLAST search of public sequence databases, the NOVl 6a protein was found to have homology to the proteins shown in the BLASTP data in Table 16E.

PFam analysis predicts that the NOVl 6a protein contains the domains shown in the Table 16F.

Example 17.

The NOVl 7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17 A.

Table 17A. NOV17 Sequence Analysis

NOV17a, CG52643-02 SEQ ID NO: 239 5573 bp DNA Sequence ORF Start: ATG at 408 ORF Stop: TGA at 2934

GGAGAGGGCTGCATTGCTGTTGCTCACTGACCTTCTTTTATGCTGGCCTTTGGTTCAGAATGGCACAT CATTCCTCGTTTTTGGCCCTCCAGCTGAACACCTGTTCTCTGTGGCACTGACTCCTCTTTCCATAGGG ACATCATACAACAGTCGCCTTTATCTGAGGTTGTGCAAAGAGGGATGGAGGAGAAAACAATGGAGAAT CCCTGGCAGATTTCCCCAGGACGAGAGAAGGATATCCAATTGCTCATCAGGGAAGGTGCTAGGTCTCC CAGCCAGACGCCCTCAGAGGCCGGTGTCAAGTCTCCCTCACCTCTGTGATGTGAAGTCAGCTCGTTCA

TGACCTGGGCAGGCAGAGGGTCAGAGGGGCAGATGGAGCACTCCTGGCCTGATGAAGACTCATCAAAA

TGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCTGGGATGG ATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGCCCAGAAG CTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGT TCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAG GCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCT CCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAG GTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTG CAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCT GTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGA AGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTAC AACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGC CCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCC ATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAA GACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAA TTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGC CAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCAT GCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTC CAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAG GGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAA GACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTT CTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCA AACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAG CCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAG CAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGG CTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCC CGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTT TGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCTTCA TCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATC GGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCAT CCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTG TGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGT GCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTA TGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAAT ACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTG GGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAAT CATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCA ATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTG GGTGAGGTATGAAGGGCCCAGAGCAGAGCCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGC CTCAAGCAGGTACGCTGTACATTTTTACAGACAAAAGCAAAAACCTGTACTCGCTTTGTGGTTCAACA

CTGGTCTCCTTGCAAGTTTCCTAGTATAAGGTATGCGCTGCTACCAAGATTGGGGTTTTTTCGTTAGG

JAAGTATGATTTATGCCTTGAGCTACGATGAGAACATATGCTGCTGTGTAAAGGGATCATTTCTGTGCC lAAGCTGCACACCGAGTGACCTGGGGACATCATGGAACCAAGGGATCCTGCTCTCCAAGCAGACACCTC

TGTCAGTTGCCTTCACATAGTCATTGTCCCTTACTGCCAGACCCAGCCAGACTTTGCCCTGACGGAGT

GGCCCGGAAGCAGAGGCCGACCAGGAGCAGGGGCCTCCCTCCCGAACTGAAAGCCCATCCGTCCTCGC

GTGGGACCGCATCTTCTCCCTCGCAGCTGCTTCTTGCTTTTCTTTCCATTTGACTTGCTGTAAGCCTG

AGGGAGAGCCAACAAGACTTACTGCATCTTGGGGGATGGGGAAATCACTCACTTTATTTTGGAAATTT

TTGATTAAAAAAAAATTTTATAATCTCAAATGCTAGTAAGCAGAAAGATGCTCTCCGAGGTCCAACTA

TATCCTTCCCTGCCTTAGGCCGAGTCTCGGGGGTGGTCACAACCCCACATCCCACAGCCAGAAAGAAC lAATGGTCATCTGAGAATACTGGCCCTGTCGACTATTGCCACCCTGCTTCTCCAAGAGCAGACCAGGCC lACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAAAAAACCAGAACAAGTTCTGTGTGCCTCC

TTTCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTACCCCAGATTCAGGGCAGACTGGGCTT

GCCTGGCAAGGTATGGGTGGCCTCCAGGCTCAATGCAGAAACCCCAAGGACACGAGTGGGGCCAGGTG

AGTTCCTGAAGCTATACCTTTTCAAAACAGATTTTGTTTTCCTACCTGTGGCCCATCCACTCCTCTCT

GGTACCCCATCCCCGCATCAGCACTGCAGAGAGAACACATTTCGGCGAGGGTTTTCTTACCCACATTC

CCCAATCAATACACACACACTGCAGAACCCAGAACAGAAGGCCACAGGCTGGCACTACTGCATTCTCC

TTATGTGTCTCAGGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAACCCACATAGCCCTCTGG JAGACCGCCTAGATCAGAGACTCAGCAAAAACAGGCTCGCCTTCCCTCTCCCACATATGAGTGGAACTT ACATGTGTCCTGGTTTGAATGATCATTTTGCAAGCCACACGGGTTGGGAGAGGTGGTCTCACCACAGA

CGTCTTTGCTAATTTGGCCACCTTCACCTACTGACATGACCAGGATTTTCCTTTGCCATTAAGGAATG

AACTCTTTCAAGGAGAGGAAACCCTAGACTCTGTGTCACTCTCAACACACACAGCTCCTTTCACTCCT

GCCTGACTGCCAAGCCACCTGCATCCCCCGCCCCAGATCTCATGAGATCAATCACTTGTATGTCTCAC

IGCAACTTGGTCCACCAAACGCCTGTCCCCTGTAACTCCTAGGGGTGCGCCTAGACAGGTACGTCTGTT

TTTTATTTTAAAAGATATGCTATGTAGATATAAGTTGAGGAAGCTCACCTCAAAAGCCTAGAATGCAG

TTTCACAGTAGCTGGGATGCATGGATGACCCATCTCACCCCTTTTTTTTTCCTGCCTCAATATCTTGA iTATGTTATGTTTACTCCCAATCTCCCATTTTTACCACTAAAATTCTCCAACTTTCATAAACTTTTTTT

TGGAAAAATTTCCATTGTATCAGCCCCTGACAGAAAAAGGATCTCTGAGCCTAAAGGAGGAAAAGTCC

CACCAACTACCAGACCAGAACACGAGCCCCTCTGGGCAGCAGGATTCCTAAGTCAAAGACCAGTTTGA

CCCAAACTGGCCTTTTAAAATAATCAGGAGTGACAGAGTCAACTTCTGCAGCACCTGCTTCTCCCCCA

CTGTCCCTTCCATCTTGGAATGTGTCTAAAAAAGCATAGCTGCCCTTTGCTGTCCTCAGAGTGCATTT

CCTGGAGACGGCAGGCTTAGGTCTCACTGACAGCATGCCAGACACAACTGAATCGAAGCAGGCCTGAA

GCCTAGGTCAGGGTTTCAGGAGTCCAGCCCCAGGAGGCAAAGTCACCAATGCAGGGAGGTAAATGCCT

TTTGGCAGGAAAACCAATAGAGTTGGTTGGGTGGGGAGTCAGGGGTGGGAGGAGAAGGAGGAAGAGGA

GGAAGGCCAGACTGGCCTGCCCTTTCTCCCATACTTCACCCCAGCAGAGGTTCATGGGACACAGTTGG

AAAGCCACTGGGAGGAAATGCCTCACTACAGGGGGGCCTCCTGTAGCAAGCCCAGCCGGTAATCCTCC iTAATGAACCCACAAGGTCAATTCACAACTGATATCTTAGCTATTAAAGAAGTACTGACTTTACCAAAA

GAATCATCAAGAAAGCTATTTATATAAACCCCCTCAGTCATTTTGAAATAAAATTAATTTTACAA

NOVl 7a, CG52643-02 SEQ ID NO: 240 842 aa MW at 93094.8kD Protein Sequence

MKPGGFWLHLTLLGASLPAALG MDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKK FCSRGSRCVLSR TGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLK GDTCTMAGYARLKNVLLALQTRLQPLQΞGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVL KKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAV HGDLRPPII KRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVP PVIRVYPESQAQEPGVAASLRCHAEGIPMPRIT LKNGVDVSTQMSKQLSLLANGSELHISSVRYEDT GAYTCIA NEVGVDEDISSLFIEDSARKTLANIL REEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHL KPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYI VAQPALSRVLWDIQAQKVLQSIGVDPLP AKLSYDKSHDQV VLS GDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGF IFNKSDPAVHKVDL.ETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS VLGPNGDVTGTPHTSPDGRFIVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQ YNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLI NGRQNTLRCEVSGIKGGTTWWVGEV

NOV17b, 259341359 SEQ ID NO: 241 2538 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

CTCGAGATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCT GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTG CCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACT GTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTC CTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGAC CCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGG AATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCAT GTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGA CGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCA GCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGC GCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGA CTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACA TGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAAT GTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAG ATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTC AGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAA GACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTT CATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAA ACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGG CACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGC AACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAG CACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCT CTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCA CAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCA CACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTT GGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAA GACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACT TCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACA GACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCAT AGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGA CCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGC AATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGG GAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCC ACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTC CTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGT GTGGGTGGGTGAGGTACTCGAG

NOV17b, 259341359 SEQ ID NO: 242 ! 846 aa MW at 93579.4kD Protein Sequence

LEMKPGGF LHLTLLGASLPAALG MDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCG KKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCF L GDTCTMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQ RLLVESLFRDLDADGNGHLSSSELAQH V KKQDLDED GCSPGD RFDD NSDSS REF 1.FQVVQ SIIAPED VSV V VG S^,^V TC AVHGDLRPPII KRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNΪTCHASGHEQLFQTΗVLQVN VPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYE DTGAYTCIAKNEVGVDEDISSLFIEDSARKTLMTIL REEGLSVGNMFYVFSDDGIIVIHPVDCΞIQR HLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLWDIQAQKVLQSIGVDP LPAKLSYDKSHDQVWVLS GDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRF GFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQA AHTHLGGYFFIQCRQDSPASAARQLLVDSVT DSVLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTES NQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQP GGTHRIMRDSGLFGQYLLTPARESLF LINGRQNTLRCEVSGIKGGTTW VGEVLE lNOV17c, 268824728 SEQ ID NO: 243 2511 bp

DNA Sequence JORF Start: at 1 ORF Stop: end of sequence

CTCGAGATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCT GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTG CCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACT GTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTC CTCAAAGGTGACACGTGCACCATTGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGAC CCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGG AATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCAT GTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGA CGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCA GCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGC GCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGA CTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACA TGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAAT GTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAG ATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTC AGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAA GACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTT CATTGAAGACTCAGCTAGAAAGACCCGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACG GTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTC ATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGC AGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACA TCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAG TCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGAT CACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCT TCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCT GCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTG CGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCC CCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGAT GTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTG GCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGG GCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTG CACATGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAAGAACTTAAA GGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGT TTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTG CGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTACTCGAG

NOV17c, 268824728 SEQ ID NO: 244 837 aa MW at 92565.3kD Protein Sequence

LEMKPGGF LHLTLLGASLPAALG MDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCG KKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLG RITVIHSKDCF LKGDTCTIAGYARL NVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQH VLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVTVGLSTVLTC AVHGDLRPPII KRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVN VPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRIT LKNGVDVSTQ S QLSLLANGSELHISSVRYE DTGAYTCIAKNEVGVDΞDISSLFIEDSARKTRLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIF MSYEEICPQREKNATQPCQ VSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDK SHDQV VLS GDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDP AVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGD VTGTPHTSPDGRFIVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAAL HMEPDLLFLELSTGKVGMLKNLKEPPAGPAQP GGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTL RCEVSGIKGGTTWWVGEVLE

[NOV17d, 268825987 SEQ ID NO: 245 2439 bp

DNA Sequence JORF Start: at 1 pRF Stop: end of sequence

CTCGAGATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCT GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCTGGG AAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCT ACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGC AGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGG CAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACT TACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTC CGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGAC CACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCA TCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGAT GATTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCA CGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGA GCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGA ATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAA TGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAA ATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCA AACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTAT CATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGA GCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTC AATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCA lAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCAC lATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACA iGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCAT TCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAG TCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTG CCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGC CTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAA CAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTG CACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCAT CTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTGCACA TGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAG CCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGG ACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGT GTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTACTCGAG

NOV17d, 268825987 SEQ ID NO: 246 813 aa MW at 89900.2kD Protein Sequence

LEMKPGGF LHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCG - FCSRGSRCVLSRKTGEPECLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQEGDS RQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTL REFYMAFQVVQLSIiAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPII KRNGLTLNFLDLEDINDFGED DSLYITKVTTIHMGNYTCHASGHEQLFQTRVLQVNVPPVIRVYPESQAQΞPGVAASLRCHAEGIPMPR IT LKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLA NILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHL PTEKIFMSYEEICPQREKNATQPCQWVSAV NVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPA LSYDKSHDQV VLSWGDVHKSRPSLQVIT EASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCV PQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAAADSPWL RVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHMEPDLLFLELSTGKVGMLKNLKE PPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTWWVGEVLE

NOVl 7e, 268825997 SEQ ID NO: 247 |2472 bp

DNA Sequence RF Start: at 1 ORF Stop: end of sequence

CTCGAGTGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGA GCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCG GGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAG TGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCA CTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTT TCCTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAG ACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGT GGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGC ATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTT GACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCT CAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCT GCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTG GACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCA CATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGA ATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTA AGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAAC TCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATG AAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTC TTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGG AAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGA GGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAAT GCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCC AGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACC CTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTG CACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCG CACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGT TTGGCTTCATCTTCAACAAGTCTGATCCTACAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTC AAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTA CTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCA CAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTC ATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCA GACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAA GCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACG GGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTAC CCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGT TCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTG GTGTGGGTGGGTGAGGTACTCGAG

NOV17e, 268825997 SEQ ID NO: 248 824 aa MW at 91376.7kD Protein Sequence

LE MDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSRGSRCVLSRKTGEPECQ CLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQ TRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLGCSPGDLLRF DDYNSDSSLTLREFYMAFQVVQLSIJAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPIIWKRNGLTLNFL DLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASL RCHAEGIPMPRIT LKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSL FIEDSARKTLANIL REEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKN ATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYD SHDQV VLSWGDV HKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPTVHKVDLETM PL KTIGLHHHGCVPQAiVIAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRF IVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELST G VGML NL EPPAGPAQP GGTHRI RDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTV VWVGEVLE

NOVl 7f, 275698334 SEQ ID NO: 249 2538 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

CTCGAGATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCT GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTG CCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACT GTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTC CTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGAC CCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGG AATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCAT GTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGA CGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCA GCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGC GCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGA CTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACA TGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAAT GTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAG ATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTC AGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAA GACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTT CATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAA ACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGG CACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGC AACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAG CACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCT CTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCA CAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCA CACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTT GGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAA GACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACT TCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACA GACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCAT AGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGA CCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGC AATCAATACAACATCTACGCGGCTCTGCACATGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGG GAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCC ACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTC CTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGT GTGGGTGGGTGAGGTACTCGAG

NOV17f, 275698334 SEQ ID NO: 250 846 aa MW at 93609.5kD Protein Sequence

LEMKPGGF LHLTLLGASLPAALG MDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCG KKFCSRGSRCVLSR TGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCF LKGDTCT AGYARL JNTVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQH

VLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYT^FQVVQLSLIAPEDRVSVTTVTVGLSTVLTC AVHGDLRPPII KRNGLTLNFLDLEDINΓJFGEDDSLYITKVTTIH GNYTCHASGHEQLFQTHVLQVN VPPVIRVYPΞSQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYE DTGAYTCIAKNΞVGVDEDISSLFIEDSARKTLANILREEGLSVGNMFYVFSDDGIIVIHPVDCEIQR HLKPTEKIFMSYEEICPQREKNATQPCQVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDP PAKLSYDKSHDQVWVLS GDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRF GFIFNKSDPAVHKVDLETMMPLKTIGLHRΉGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVT DSVLGPNGDVTGTPHTSPDGRFIVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTES QYNIYAALHMEPDLLFLELSTGKVGMLKNLKEPPAGPAQP GGTHRIMRDSGLFGQYLLTPARESLF LINGRQNTLRCEVSGIKGGTTWWVGEVLE

NOV17g, CG52643-04 SEQ ID NO: 251 2538 bp

DNA Sequence ORF Start: ATG at7lθRF Stop: endofsequence

CTCGAGATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCT

GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTG CCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACT GTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTC CTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGAC CCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGG AATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCAT GTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGA CGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCA GCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGC GCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGA CTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACA TGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAAT GTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAG ATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTC AGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAA GACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTT CATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAA ACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGG CACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGC AACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAG CACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCT CTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCA CAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCA CACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTT GGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAA GACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACT TCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACA GACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCAT AGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGA CCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGC AATCAATΆCAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGG GAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCC ACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTC CTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGT GTGGGTGGGTGAGGTA

NOV17g, CG52643-04 SEQ ID NO: 252842 aa (MW at 93094.8kD Protein Sequence KPGGFWLHLTLLGASLPAALG MDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGK FCSRGSRCVLSRKTGΞPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLK GDTCT AGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVL KKQD DED GCSPGDL RFDDYNSDSSL REF ^FQ VQ SI_J PEDRVSVTTVT G STV TCA HGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVP PVIRVYPESQAQEPGVAASLRCHAEGIPMPRIT L NGVDVSTQMSKQLSLLANGSELHISSVRYEDT GAYTCIA NEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHL KPTEKIFMSYEEICPQREIG^ATQPCQ ^SAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLP AKLSYDKSHDQVVΠ/LSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGF IFNKSDPAVHKVDLΞTMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS VLGPNGDVTGTPHTSPDGRFIVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQ YNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQP GGTHRIMRDSGLFGQYLLTPARESLFLI NGRQNTLRCEVSGIKGGTTW VGEV

NOV17h, 301380586 JSEQ ID NO: 253 2548 bp

DNA Sequence ORF Start: at 2 ORF Stop: end ofsequence

CACCGGATCCACCATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGG CTGCGCTGGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCA GAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTC CTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAAT GCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAA AACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGA CTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCAC TCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTC CTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGC TCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCC GATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTT CAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCT GACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACT TCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACC ATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCA GGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCA GCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTC TCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCG GTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCT CGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGC GTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGAT CCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAA AAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCC CAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGT GGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGG ACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTC ATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACAT CAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGC CCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGC GGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAG TGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGC GCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAG ATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCAC TGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGT CCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGG GGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTC ACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCA CAGTGGTGTGGGTGGGTGAGGTAGAATTCGGC

NOV17h, 301380586 SEQ ID NO: 254 849 aa MW at 93774.5kD Protein Sequence

TGSTMKPGGF LHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLAS CGKKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKD

CFLKGDTCT^GYARLKNVLIJALQTRLQPLQEGDSRQDPASQ KLLVESLFRDLDADGNGHLSSSEIJA

QHVLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVTVGLSTVL TCAVHGDLRPPII KRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQ VNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRIT LKNGVDVSTQMSKQLSLLANGSELHISSVR YEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEI QRHLKPTEKIFMSYEEICPQREKNATQPCQ VSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGV DPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHI RFGFIFNKSDPAVHKVDLET PLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDS VTDSVLGPNGDVTGTPHTSPDGRFIVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFT ESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQP GGTHRIMRDSGLFGQYLLTPARES LFLINGRQNTLRCEVSGIKGGTTW VGEVEFG

NOV17i, 289087852 SEQ ID NO: 255 1842bp DNA Sequence ORF Start: at 1 JORF Stop: end ofsequence

CTCGAGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAA GCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCC TGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAG CTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGC ACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTT GGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGC GAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGT GGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCC TGTGGCGAGAGGAAGATGCATCCACGTGGCCGGTTTCTTGTGTGTTCAATGCTGCGTGTGACCCTGCC CAGGGGCCGACTGCTTGGAGGGCATGCCCATTCCATTTGCTCCTCCCAGGCCTCAGCGTGGGAAACAT GTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACC TCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACC CAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACT GAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGC CGGCTAAGCTGTCCTATGGCAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAG TCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACC CTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCT TCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACC ATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTT CATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACT CTGTGCTTGGCCCCAATGGCGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTC AGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCT GTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATC AATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAG GTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAG AATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCA TCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGG CTCGAG

NOV17L 289087852 SEQ ID NO: 256. 614 aa MW at 67956.6kD Protein Sequence LEGLSTVLTCAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQ LFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRIT LKNGVDVSTQMSKQLSLLANGS ELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANIL REEDAST PVSCVFNAACDPA QGPTAWRACPFHLLLPGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQRE NAT QPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYG SHDQV VLSWGDVHK SRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVH VDLET MPLKT IGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIV SAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELSTGK VGMLKNLIOSPPAGPAQP GGTHRIMRDSGLFGQYLLTPARESLFLINGRQN LRCEVSGIKGGTTVV LE

NOV17J, 289081920 SEQ ID NO: 257 1713 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

CTCGAGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAA GCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCC TGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAG CTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGC ACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTT GGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGC GAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGT GGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCGCCTCAGCGTGG GAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAG AGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAA TGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGC CAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGAC CCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGT GCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCC GCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGG TTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCT CAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCT ACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTC ACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTT CATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCC AGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAA AGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCAC GGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTA CCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTG TTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGT GGTGTGGCTCGAG

NOV17J, 289081920 SEQ ID NO: 258 571 aa MW at 63363.4kD Protein Sequence

LEGLSTVLTCAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQ LFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGS ELHISSVRYΞDTGAYTCIAKNEVGVDEDISSLFIEDSARKTRLSVGNMFYVFSDDGIIVIHPVDCEIQ RHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVD PLPA LSYDKSHDQV VLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIR FGFIFNKSDPAVHKVDLET MPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSV TDSVLGPNGDVTGTPHTSPDGRFIVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTE SNQYNIYAALHTEPDLLFLELSTGϊVGMLKNLKEPPAGPAQP GGTHRIMRDSGLFGQYLLTPARESL FLINGRQNTLRCEVSGIKGGTTWWLE

NOV17k, 289098038 SEQ ID NO: 259 1740 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

CTCGAGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAA GCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCC TGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAG CTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGC ACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTT GGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGC GAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGT GGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCC TGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTC ATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGA AGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCC GGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAG AAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCA AGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCA GCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCA ACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAA GGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGG CCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCT GCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCAC CCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGC AGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGAC TTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCC GGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCG CAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTAC CTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGT GTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGCTCGAG

NOV17k, 289098038 SEQ ID NO: 260 580 aa MW at 64389.6kD Protein Sequence

LEGLSTVLTCAVHGDLRPPII KRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQ LFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRIT LKNGVDVSTQMSKQLSLLANGS ELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANIL REEGLSVGNMFYVFSDDGIIV IHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQ VSAVNVRNRYIYVAQPALSRVLWDIQAQ KVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPP TNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASA ARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISD LAFQRSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQP GGTHRIMRDSGLFGQY LLTPARESLFLINGRQNTLRCEVSGI GGTTW LE

NOV171, 311060818 SEQ ID NO: 261 2508 bp DNA Sequence ORF Start: at 13 ORF Stop: end of sequence

GCCAGGTGATGATATCTCAGATTCGCCTTCACCGGATCCTGGATGGACCCAGGAACCAGCAGAGGCCC GGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGC TTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTG CTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGT GTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAA AGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTAC GCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAG ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCA ATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTA CTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCG CGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCA CAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATC TGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGA TTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACG AGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGC CAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAAT CACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATG GGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAAT GAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAA CATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCA TCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGC TATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAA TGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAG CCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACAT GACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGA AGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTC CCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTC CACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCC CCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCT CTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACA GGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCA CGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCT CAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACG GAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCC ACCCGCAGGGCCAGCTCAGCCCCGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGAC AGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGT GAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTAGAATTCGGC

NOV171, 311060818 SEQ ID NO: 262 832 aa MW at 92208.6kD Protein Sequence | 1

YLRFAFTGSW DPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGK FCSRGSRCVLSRK TGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDTCT AGYARLK NVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVL KQDLDEDLLGCS PGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPIIWKRN GLTLNFLDLEDINDFGEDDSLYITKVTTIH GNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQAQE PGVAASLRCHAEGIPMPRIT LKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGV DEDISSLFIEDSARKTLANIL REEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEI CPQREKNATQPCQ VSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAICLSYDKSHDQV VLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVD LETMMPLKTIGLHHHGCVPQA AHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPH TSPDGRFIVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDL LFLELSTGKVGMLKNLKEPPAGPAQPRGGTHRI RDSGLFGQYLLTPARESLFLINGRQNTLRCEVSG IKGGTTW VGEVEFG

NOV17m, 311885703 SEQ ID NO: 263 2479 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence

CACCGGATCCTGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAG AGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCC TGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATG CCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAA ACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGAC TGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACT CCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCC TGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCT CAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCG ATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTC AGCTCAGCCTCGCCCCCGAGGACAGGGCCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTG ACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTT CCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCA TCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAG GTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAG CCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCT CAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGG TATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTC GCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCG TGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATC CAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAA AAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCC AGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTG GACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGA CGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCA TCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATC ;AGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCC CCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCG GCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGT GTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCG CTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGA TCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACT GAAAGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTC CACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGG GTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCA CTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCAC AGTGGTGTGGGTGGGTGAGGTAGAATTCGGC

NOVl 7m, 311885703 SEQ ID NO: 264 826 aa MW at 914l2.7kD Protein Sequence

TGSWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSRGSRCVLSRKTGEPEC QCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLAL QTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVL KQDLDEDLLGCSPGDLLR FDDYNSDSSLTLREFYMAFQVVQLSLAPEDRASVTTVTVGLSTVLTCAVHGDLRPPIIWKRNGLTLNF LDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQAQΞPGVAAS LRCHAEGIPMPRIT LKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISS LFIEDSARKTLANIL REEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREK NATQPCQV^SAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQV VLS GD VHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFN SDPAVHKVDLETMMP LKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGR FIVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNI AALHTEPDLLFLELS TGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTT W VGEVEFG

NOV17n, CG52643-01 SEQ ID NO: 265 1689 bp

DNA Sequence pRF Start: ATG at 199 |ORF Stop: TGA at 1147

TAGAATTCAGCGGCCGCTTAATTCTAGAACGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGT

GCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCC

TGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCC

GGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGA CAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAG ATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAA GACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGAC CCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTG TGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCA ATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGA GGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCG GCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCA GAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCC CAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAG CCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCC AAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCT TGCAAACATCCTGTGGCGAGAGGAAGGTACCAAGCTTCATTGTTTTGCGTCATGCCTGTGATCACGTG TGTTTGGTTCTATGATGGGCCGTCTTTCCATGATCTGCCACCAGCTTTCCCACACAAAGCAGCCCTAT

GGGAGCAGGAAGTCAATGTCAAATTCAAGTGGCATATGCATTGAATCAAATTTAAAATGTACTCCTGT

CTTTAATGAGAAATTTTTAAATGCAAAGCTTTCATTAAAAGTGGCTTGTAACCTCTGCTGAAGCAGAA

CAGTTGGTAAGGGTTCCTGGTCAGATCTGGGCCTTAAACTTTTTTCCAGTAGCTGACTGGTGTTGGGT

TTAGTGTTTTGCCTATCTTGTGTGGTTTTAAAAAGACAAAACAAGTTGTAGATCTCTACTAGATAGTC

ACTGTACCTTAAATATGCTTTGATTGAGGAAAACCCGAGGAAAAAGCTGCCATGATTTCTGCCAATGT

ATATTTTTAAATGTATAGATGTTTAGAAACATATTTATCAAGCAAATCTTTAGTAAGTTGAGCCATAT

IGAAGTTGCCATTTTTGTGCATCAAAGTGGTCTAAGATTGACAATTTCATATGGCTGA NOV17n, CG52643-01 SEQ ID NO: 266 316 aa MW at 35059.2kD Protein Sequence

MAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDL DEDLLGCSPGDLLRFDDYNSDSSLTLREFY AFQVVQLSLAPΞDRVSVTTVTVGLSTVLTCAVHGDLR PPII KRNGLTLNFLDLEDI1TOFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRV YPESQAQEPGVAASLRCHAEGIPMPRIT LKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTC IAKNEVGVDEDISSLFIEDSARKTLANIL REEGT LHCFASCL

NOV17o, CG52643-03 SEQ ID NO: 267 914 bp DNA Sequence ORF Start: at 12 ORF Stop: end of sequence

TGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGAGGAGTCACAGGCA

GAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTC

CTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAAT

GCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAA

AACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCGCCGTCATCCACAGCAAGGA

CTGTTTCCTCAAAGGTGACACGTGCACCATGGGCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCAC

TCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTC

CTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGC

TCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCC

GATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTT

CAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCC

GACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACT

TCCTGGACTTGGAAGACATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGG

GGGACCACAGTGGTGTGGGTGGGTGAGGTA

NOV17o, CG52643-03 SEQ ID NO: 268 ' 301 aa MW at 33218.2kD Protein Sequence

WMDPGTSRGPDVGVEESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSRGSRCVLSRKTGEPECQCL EACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRIAVIHSKDCFLKGDTCTMGGYARLKNVLLALQTR LQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLGCSPGDLLRFDD YNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVPTCAVHGDLRPPII KRNGLTLNFLDL EDINGRQNTLRCEVSGI GGTTW VGEV

|NOV17p, CG52643-05 SEQ ID NO: 269 2548 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: end of sequence

CACCGGATCCACCATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGG

CTGCGCTGGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCA GAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTC CTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAAT GCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAA AACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGA CTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCAC TCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTC CTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGC TCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCC GATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTT CAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCT GACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACT TCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACC ATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCA GGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCA GCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTC TCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCG GTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCT CGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGC GTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGAT CCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAA AAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCC CAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGT GGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGG ACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTC ATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACAT CAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGC CCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGC GGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAG TGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGC GCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAG ATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCAC TGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGT CCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGG GGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTC ACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCA CAGTGGTGTGGGTGGGTGAGGTA

|NOV17p, CG52643-05 |SEQ ID NO: 270 842 aa MW at 93094.8kD Protein Sequence

MKPGGF LHLTLLGASLPAALG MDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKK FCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHS DCFLK GDTCTMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVL KKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVTVGLSTVLTCAV HGDLRPPII KRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVP PVIRVYPESQAQEPGVAASLRCHAEGIPMPRIT L NGVDVSTQMSKQLSLLANGSELHISSVRYEDT GAYTCIAKNEVGVDΞDISSLFIEDSARKTLANIL REEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHL KPTEKIFMSYEEICPQREKNATQPCQ VSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLP AKLSYDKSHDQV VLS GDVH SRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGF IFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS VLGPNGDVTGTPHTSPDGRFIVSAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQ YNIYAALHTEPDLLFLELSTGKVGML NLKEPPAGPAQP GGTHRIMRDSGLFGQYLLTPARESLFLI NGRQNTLRCEVSGIKGGTTWWVGEV

NOV17q, CG52643-06 SEQ ID NO: 271 2460 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

TGGATGGACCCAGGAACCAGCAGAGGCCC

GGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGC

TTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTG

CTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGT

GTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAA

AGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTAC

GCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAG

ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCA

ATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTA

CTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCG

CGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCA

CAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATC

TGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGA

TTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACG

AGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGC

CAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAAT

CACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATG

GGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAAT

GAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAA

CATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCA

TCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGC

TATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAA

TGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAG

CCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACAT GACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGA AGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTC CCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTC CACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCC CCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCT CTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACA GGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCA CGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCT CAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACG GAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCC ACCCGCAGGGCCAGCTCAGCCCCGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGAC AGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGT GAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTA

NOV17q, CG52643-06 SEQ ID NO: 272 820 aa MW at 90832. lkD

Protein Sequence j MDPGTSRGPDVGVGESQAEΞPRSFEVTRREGLSSHNELLASCGKKFCSRGSRCVLSRKTGEPECQCL EACRPSYVPVCGSDGRFYENHCKLHRAACLLGK^ITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTR LQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLGCSPGDLLRFDD YNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPII RNGLTLNFLDL ED NBFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRC HAEGIPMPRIT L NGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFI EDSARKTLANIL REEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNAT QPCQ VSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS GDVHK SRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKT IGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIV SAAADSP LHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELSTGK VGMLKNLKEPPAGPAQPRGGTHRIMRDSGLFGQYLLTPARESLFLINGRQOTLRCEVSGIKGGTTVVW VGEV

NOV17r, 13382322 SNP for SEQ ID NO: 273 5573 bp SNP: 517 G/A

CG52643-02 ORF Start: ATG at ORF Stop: TGA at 2934

DNA Sequence 408

GGAGAGGGCTGCATTGCTGTTGCTCACTGACCTTCTTTTATGCTGGCCTTTGGTTCAGAATGGCACATCA

TTCCTCGTTTTTGGCCCTCCAGCTGAACACCTGTTCTCTGTGGCACTGACTCCTCTTTCCATAGGGACAT

CATACAACAGTCGCCTTTATCTGAGGTTGTGCAAAGAGGGATGGAGGAGAAAACAATGGAGAATCCCTGG

CAGATTTCCCCAGGACGAGAGAAGGATATCCAATTGCTCATCAGGGAAGGTGCTAGGTCTCCCAGCCAGA

CGCCCTCAGAGGCCGGTGTCAAGTCTCCCTCACCTCTGTGATGTGAAGTCAGCTCGTTCATGACCTGGGC lAGGCAGAGGGTCAGAGGGGCAGATGGAGCACTCCTGGCCTGATGAAGACTCATCAAAATGAAACCAGGAG

GCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCTGGGATGGATGGACCCAGGAAC CAGCAGAGGCCCGGATGTGGGTGTGGAGGAGTCACAGGCAGAGGAGCCCAGAAGCTTTGAAGTCACAAGA AGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCC GGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGT GCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTG GGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCT ACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAG ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAAT GGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTG GTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTT CTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACC GTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCA ACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACAT CACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAG ACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTG GAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGG CGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGC AGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATA TCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCT CAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAG ATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAA AAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCA GCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGAC CCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGC ACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCAC ACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGC TTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCA TCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCAT CCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTG CTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTG CAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCT GCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATC TACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGA AGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAG TGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAAC ACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTATGAAGGG

CCCAGAGCAGAGCCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGCCTCAAGCAGGTACGCTGT jACATTTTTACAGACAAAAGCAAAAACCTGTACTCGCTTTGTGGTTCAACACTGGTCTCCTTGCAAGTTTC

CTAGTATAAGGTATGCGCTGCTACCAAGATTGGGGTTTTTTCGTTAGGAAGTATGATTTATGCCTTGAGC

TACGATGAGAACATATGCTGCTGTGTAAAGGGATCATTTCTGTGCCAAGCTGCACACCGAGTGACCTGGG

GACATCATGGAACCAAGGGATCCTGCTCTCCAAGCAGACACCTCTGTCAGTTGCCTTCACATAGTCATTG

TCCCTTACTGCCAGACCCAGCCAGACTTTGCCCTGACGGAGTGGCCCGGAAGCAGAGGCCGACCAGGAGC

AGGGGCCTCCCTCCCGAACTGAAAGCCCATCCGTCCTCGCGTGGGACCGCATCTTCTCCCTCGCAGCTGC

TTCTTGCTTTTCTTTCCATTTGACTTGCTGTAAGCCTGAGGGAGAGCCAACAAGACTTACTGCATCTTGG

GGGATGGGGAAATCACTCACTTTATTTTGGAAATTTTTGATTAAAAAAAAATTTTATAATCTCAAATGCT

AGTAAGCAGAAAGATGCTCTCCGAGGTCCAACTATATCCTTCCCTGCCTTAGGCCGAGTCTCGGGGGTGG

TCACAACCCCACATCCCACAGCCAGAAAGAACAATGGTCATCTGAGAATACTGGCCCTGTCGACTATTGC

CACCCTGCTTCTCCAAGAGCAGACCAGGCCACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAA

AAAACCAGAACAAGTTCTGTGTGCCTCCTTTCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTA

CCCCAGATTCAGGGCAGACTGGGCTTGCCTGGCAAGGTATGGGTGGCCTCCAGGCTCAATGCAGAAACCC

CAAGGACACGAGTGGGGCCAGGTGAGTTCCTGAAGCTATACCTTTTCAAAACAGATTTTGTTTTCCTACC

TGTGGCCCATCCACTCCTCTCTGGTACCCCATCCCCGCATCAGCACTGCAGAGAGAACACATTTCGGCGA

GGGTTTTCTTACCCACATTCCCCAATCAATACACACACACTGCAGAACCCAGAACAGAAGGCCACAGGCT

GGCACTACTGCATTCTCCTTATGTGTCTCAGGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAAC

CCACATAGCCCTCTGGAGACCGCCTAGATCAGAGACTCAGCAAAAACAGGCTCGCCTTCCCTCTCCCACA

TATGAGTGGAACTTACATGTGTCCTGGTTTGAATGATCATTTTGCAAGCCACACGGGTTGGGAGAGGTGG

TCTCACCACAGACGTCTTTGCTAATTTGGCCACCTTCACCTACTGACATGACCAGGATTTTCCTTTGCCA

TTAAGGAATGAACTCTTTCAAGGAGAGGAAACCCTAGACTCTGTGTCACTCTCAACACACACAGCTCCTT

TCACTCCTGCCTGACTGCCAAGCCACCTGCATCCCCCGCCCCAGATCTCATGAGATCAATCACTTGTATG

TCTCACGCAACTTGGTCCACCAAACGCCTGTCCCCTGTAACTCCTAGGGGTGCGCCTAGACAGGTACGTC

TGTTTTTTATTTTAAAAGATATGCTATGTAGATATAAGTTGAGGAAGCTCACCTCAAAAGCCTAGAATGC

AGTTTCACAGTAGCTGGGATGCATGGATGACCCATCTCACCCCTTTTTTTTTCCTGCCTCAATATCTTGA

TATGTTATGTTTACTCCCAATCTCCCATTTTTACCACTAAAATTCTCCAACTTTCATAAACTTTTTTTTG jGAAAAATTTCCATTGTATCAGCCCCTGACAGAAAAAGGATCTCTGAGCCTAAAGGAGGAAAAGTCCCACC

AACTACCAGACCAGAACACGAGCCCCTCTGGGCAGCAGGATTCCTAAGTCAAAGACCAGTTTGACCCAAA

CTGGCCTTTTAAAATAATCAGGAGTGACAGAGTCAACTTCTGCAGCACCTGCTTCTCCCCCACTGTCCCT

TCCATCTTGGAATGTGTCTAAAAAAGCATAGCTGCCCTTTGCTGTCCTCAGAGTGCATTTCCTGGAGACG

GCAGGCTTAGGTCTCACTGACAGCATGCCAGACACAACTGAATCGAAGCAGGCCTGAAGCCTAGGTCAGG GTTTCAGGAGTCCAGCCCCAGGAGGCAAAGTCACCAATGCAGGGAGGTAAATGCCTTTTGGCAGGAAAAC CAATAGAGTTGGTTGGGTGGGGAGTCAGGGGTGGGAGGAGAAGGAGGAAGAGGAGGAAGGCCAGACTGGC

CTGCCCTTTCTCCCATACTTCACCCCAGCAGAGGTTCATGGGACACAGTTGGAAAGCCACTGGGAGGAAA TGCCTCACTACAGGGGGGCCTCCTGTAGCAAGCCCAGCCGGTAATCCTCCTAATGAACCCACAAGGTCAA TTCACAACTGATATCTTAGCTATTAAAGAAGTACTGACTTTACCAAAAGAATCATCAAGA AAGCTATTTATATAAACCCCCTCAGTCATTTTGAAATAAAATTAATTTTACAA

NOV17r, 13382322 SNP for SEQ ID NO: 842 aa SNP: Gly to Glu at position 37

CG52643-02 274

Protein Sequence KPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVEESQAEEPRSFEVTRREGLSSHNELLASCGKKFC SRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDTC TMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLD EDLLGCSPGDLLRFDDYNSDSSLTLREFY AFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPI I KRNGLTIiNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTRVLQVNVPPVIRVYPESQ AQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVG VDEDISSLFIEDSARKTLANIL REEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEIC PQREKNATQPCQV tSAVNVRϊπiYIYVAQPALSRVLVVDIQAQ VLQSIGVDPLPAKLSYDKSHDQVWVL.S WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMM PLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRF IVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELSTGK VGMLKNLKEPPAGPAQP GGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVV VG EV

NOV17s, 13382324 SNP for SEQ ID NO: 275 5573 bp SNP: 880 G/A

CG52643-02 ORF Start: ATG at ORF Stop: end of sequence

DNA Sequence 408

GGAGAGGGCTGCATTGCTGTTGCTCACTGACCTTCTTTTATGCTGGCCTTTGGTTCAGAATGGCACATCA

TTCCTCGTTTTTGGCCCTCCAGCTGAACACCTGTTCTCTGTGGCACTGACTCCTCTTTCCATAGGGACAT

CATACAACAGTCGCCTTTATCTGAGGTTGTGCAAAGAGGGATGGAGGAGAAAACAATGGAGAATCCCTGG

CAGATTTCCCCAGGACGAGAGAAGGATATCCAATTGCTCATCAGGGAAGGTGCTAGGTCTCCCAGCCAGA

CGCCCTCAGAGGCCGGTGTCAAGTCTCCCTCACCTCTGTGATGTGAAGTCAGCTCGTTCATGACCTGGGC

AGGCAGAGGGTCAGAGGGGCAGATGGAGCACTCCTGGCCTGATGAAGACTCATCAAAATGAAACCAGGAG

GCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCTGGGATGGATGGACCCAGGAAC CAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGCCCAGAAGCTTTGAAGTCACAAGA AGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCC GGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGT GCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTG GGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCT ACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCATCTGCAGCCACTCCAAGAAGGAGACAGCAG ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAAT GGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTG GTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTT CTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACC GTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCA ACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACAT CACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAG ACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTG GAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGG CGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGC AGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATA TCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCT CAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAG ATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAA AAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCA GCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGAC CCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGC ACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCAC ACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGC TTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCA TCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCAT CCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTG CTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTG CAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCT GCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATC TACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGA AGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAG TGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAAC ACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTATGAAGGG

CCCAGAGCAGAGCCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGCCTCAAGCAGGTACGCTGT

ACATTTTTACAGACAAAAGCAAAAACCTGT

ACTCGCTTTGTGGTTCAACACTGGTCTCCTTGCAAGTTTCCTAGTATAAGGTATGCGCTGCTACCAAGAT GGGGTTTTTTCGTTAGGAAGTATGATTTATGCCTTGAGCTACGATGAGAACATATGCTGCTGTGTAAAG

GGATCATTTCTGTGCCAAGCTGCACACCGAGTGACCTGGGGACATCATGGAACCAAGGGATCCTGCTCTC

CAAGCAGACACCTCTGTCAGTTGCCTTCACATAGTCATTGTCCCTTACTGCCAGACCCAGCCAGACTTTG

CCCTGACGGAGTGGCCCGGAAGCAGAGGCCGACCAGGAGCAGGGGCCTCCCTCCCGAACTGAAΛGCCCAT

CCGTCCTCGCGTGGGACCGCATCTTCTCCCTCGCAGCTGCTTCTTGCTTTTCTTTCCATTTGACTTGCTG

TAAGCCTGAGGGAGAGCCAACAAGACTTACTGCATCTTGGGGGATGGGGAAATCACTCACTTTATTTTGG

AAATTTTTGATTAAAAAAAAATTTTATAATCTCAAATGCTAGTAAGCAGAAAGATGCTCTCCGAGGTCCA

ACTATATCCTTCCCTGCCTTAGGCCGAGTCTCGGGGGTGGTCACAACCCCACATCCCACAGCCAGAAAGA

ACAATGGTCATCTGAGAATACTGGCCCTGTCGACTATTGCCACCCTGCTTCTCCAAGAGCAGACCAGGCC iACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAAAAAACCAGAACAAGTTCTGTGTGCCTCCTT

TCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTACCCCAGATTCAGGGCAGACTGGGCTTGCCT

GGCAAGGTATGGGTGGCCTCCAGGCTCAATGCAGAAACCCCAAGGACACGAGTGGGGCCAGGTGAGTTCC TGAAGCTATACCTTTTCAAAACAGATTTTGTTTTCCTACCTGTGGCCCATCCACTCCTCTCTGGTACCCC

ATCCCCGCATCAGCACTGCAGAGAGAACACATTTCGGCGAGGGTTTTCTTACCCACATTCCCCAATCAAT

ACACACACACTGCAGAACCCAGAACAGAAGGCCACAGGCTGGCACTACTGCATTCTCCTTATGTGTCTCA

GGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAACCCACATAGCCCTCTGGAGACCGCCTAGATC

AGAGACTCAGCAAAAACAGGCTCGCCTTCCCTCTCCCACATATGAGTGGAACTTACATGTGTCCTGGTTT

GAATGATCATTTTGCAAGCCACACGGGTTGGGAGAGGTGGTCTCACCACAGACGTCTTTGCTAATTTGGC

CACCTTCACCTACTGACATGACCAGGATTTTCCTTTGCCATTAAGGAATGAACTCTTTCAAGGAGAGGAA

ACCCTAGACTCTGTGTCACTCTCAACACACACAGCTCCTTTCACTCCTGCCTGACTGCCAAGCCACCTGC

ATCCCCCGCCCCAGATCTCATGAGATCAATCACTTGTATGTCTCACGCAACTTGGTCCACCAAACGCCTG

TCCCCTGTAACTCCTAGGGGTGCGCCTAGACAGGTACGTCTGTTTTTTATTTTAAAAGATATGCTATGTA

GATATAAGTTGAGGAAGCTCACCTCAAAAGCCTAGAATGCAGTTTCACAGTAGCTGGGATGCATGGATGA

CCCATCTCACCCCTTTTTTTTTCCTGCCTCAATATCTTGATATGTTATGTTTACTCCCAATCTCCCATTT

TTACCACTAAAATTCTCCAACTTTCATAAACTTTTTTTTGGAAAAATTTCCATTGTATCAGCCCCTGACA

GAAAAAGGATCTCTGAGCCTAAAGGAGGAAAAGTCCCACCAACTACCAGACCAGAACACGAGCCCCTCTG

GGCAGCAGGATTCCTAAGTCAAAGACCAGTTTGACCCAAACTGGCCTTTTAAAATAATCAGGAGTGACAG iAGTCAACTTCTGCAGCACCTGCTTCTCCCCCACTGTCCCTTCCATCTTGGAATGTGTCTAAAAAAGCATA

GCTGCCCTTTGCTGTCCTCAGAGTGCATTTCCTGGAGACGGCAGGCTTAGGTCTCACTGACAGCATGCCA

GACACAACTGAATCGAAGCAGGCCTGAAGCCTAGGTCAGGGTTTCAGGAGTCCAGCCCCAGGAGGCAAAG

TCACCAATGCAGGGAGGTAAATGCCTTTTGGCAGGAAAACCAATAGAGTTGGTTGGGTGGGGAGTCAGGG

GTGGGAGGAGAAGGAGGAAGAGGAGGAAGGCCAGACTGGCCTGCCCTTTCTCCCATACTTCACCCCAGCA

GAGGTTCATGGGACACAGTTGGAAAGCCACTGGGAGGAAATGCCTCACTACAGGGGGGCCTCCTGTAGCA

AGCCCAGCCGGTAATCCTCCTAATGAACCCACAAGGTCAATTCACAACTGATATCTTAGCTATTAAAGAA

GTACTGACTTTACCAAAAGAATCATCAAGAAAGCTATTTATATAAACCCCCTCAGTCATTTTGAAATAAA

ATTAATTTTACAA

NOV17s, 13382324 SNP for SEQ ID NO: 842 aa SNP: Arg to His at position

CG52643-02 276 158

Protein Sequence KPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFC SRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDTC TMAGYARLKNVLIiALQTHLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLD EDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPI IWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQ AQEPGVAASLRCHAEGIPMPRITWL NGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVG VDEDISSLFIEDSARKTLANILWREEGLSVGN FYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEIC PQRE NATQPCQ VSAVIWRI^YIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS GDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLET M PLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRF IVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELSTGK VGMLKNLF^PPAGPAQP GGTHRI RDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVG EV

NOV17t, 13381678 SNP for SEQ ID NO: 277 5573 bp SNP: 2677 C/T CG52643-02 ORF Start: ATG at ORF Stop: end of sequence DNA Sequence 408

GGAGAGGGCTGCATTGCTGTTGCTCACTGACCTTCTTTTATGCTGGCCTTTGGTTCAGAATGGCACATCA

TTCCTCGTTTTTGGCCCTCCAGCTGAACACCTGTTCTCTGTGGCACTGACTCCTCTTTCCATAGGGACAT

CATACAACAGTCGCCTTTATCTGAGGTTGTGCAAAGAGGGATGGAGGAGAAAACAATGGAGAATCCCTGG

CAGATTTCCCCAGGACGAGAGAAGGATATCCAATTGCTCATCAGGGAAGGTGCTAGGTCTCCCAGCCAGA

CGCCCTCAGAGGCCGGTGTCAAGTCTCCCTCACCTCTGTGATGTGAAGTCAGCTCGTTCATGACCTGGGC

AGGCAGAGGGTCAGAGGGGCAGATGGAGCACTCCTGGCCTGATGAAGACTCATCAAAATGAAACCAGGAG

GCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCTGGGATGGATGG

ACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGCCCAGAAGCTTTGA

AGTCACAAGA

AGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCC

GGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGT

GCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTG

GGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCT

ACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAG

ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAAT

GGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTG

GTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTT

CTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACC

GTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCA

ACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACAT

CACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAG

ACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTG

GAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGG

CGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGC

AGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATA

TCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCT

CAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAG

ATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAA

AAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCA

GCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGAC

CCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGC

ACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCAC

ACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGC

TTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCA

TCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCAT

CCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTG

CTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTG

CAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCT

GCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATC

TACGCGGCTCTGCACATGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGA

AGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAG

TGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAAC

ACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTATGAAGGG

CCCAGAGCAGAGCCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGCCTCAAGCAGGTACGCTGT

ACATTTTTACAGACAAAAGCAAAAACCTGTACTCGCTTTGTGGTTCAACACTGGTCTCCTTGCAAGTTTC

CTAGTATAAGGTATGCGCTGCTACCAAGATTGGGGTTTTTTCGTTAGGAAGTATGATTTATGCCTTGAGC

TACGATGAGAACATATGCTGCTGTGTAAAGGGATCATTTCTGTGCCAAGCTGCACACCGAGTGACCTGGG

GACATCATGGAACCAAGGGATCCTGCTCTCCAAGCAGACACCTCTGTCAGTTGCCTTCACATAGTCATTG

TCCCTTACTGCCAGACCCAGCCAGACTTTGCCCTGACGGAGTGGCCCGGAAGCAGAGGCCGACCAGGAGC

AGGGGCCTCCCTCCCGAACTGAAAGCCCATCCGTCCTCGCGTGGGACCGCATCTTCTCCCTCGCAGCTGC

TTCTTGCTTTTCTTTCCATTTGACTTGCTGTAAGCCTGAGGGAGAGCCAACAAGACTTACTGCATCTTGG

GGGATGGGGAAATCACTCACTTTATTTTGGAAATTTTTGATTAAAAAAAAATTTTATAATCTCAAATGCT

1AGTAAGCAGAAAGATGCTCTCCGAGGTCCAACTATATCCTTCCCTGCCTTAGGCCGAGTCTCGGGGGTGG

TCACAACCCCACATCCCACAGCCAGAAAGAACAATGGTCATCTGAGAATACTGGCCCTGTCGACTATTGC

CACCCTGCTTCTCCAAGAGCAGACCAGGCCACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAA

JAAAACCAGAACAAGTTCTGTGTGCCTCCTTTCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTA CCCCAGATTCAGGGCAGACTGGGCTTGCCTGGCAAGGTATGGGTGGCCTCCAGGCTCAATGCAGAAACCC

CAAGGACACGAGTGGGGCCAGGTGAGTTCCTGAAGCTATACCTTTTCAAAACAGATTTTGTTTTCCTACC jTGTGGCCCATCCACTCCTCTCTGGTACCCCATCCCCGCATCAGCACTGCAGAGAGAACACATTTCGGCGA

GGGTTTTCTTACCCACATTCCCCAATCAATACACACACACTGCAGAACCCAGAACAGAAGGCCACAGGCT

GGCACTACTGCATTCTCCTTATGTGTCTCAGGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAAC

CCACATAGCCCTCTGGAGACCGCCTAGATCAGAGACTCAGCAAAAACAGGCTCGCCTTCCCTCTCCCACA

TATGAGTGGAACTTACATGTGTCCTGGTTTGAATGATCATTTTGCAAGCCACACGGGTTGGGAGAGGTGG

TCTCACCACAGACGTCTTTGCTAATTTGGCCACCTTCACCTACTGACATGACCAGGATTTTCCTTTGCCA

TTAAGGAATGAACTCTTTCAAGGAGAGGAAACCCTAGACTCTGTGTCACTCTCAACACACACAGCTCCTT

TCACTCCTGCCTGACTGCCAAGCCACCTGCATCCCCCGCCCCAGATCTCATGAGATCAATCACTTGTATG

TCTCACGCAACTTGGTCCACCAAACGCCTGTCCCCTGTAACTCCTAGGGGTGCGCCTAGACAGGTACGTC iTGTTTTTTATTTTAAAAGATATGCTATGTAGATATAAGTTGAGGAAGCTCACCTCAAAAGCCTAGAATGC

AGTTTCACAGTAGCTGGGATGCATGGATGACCCATCTCACCCCTTTTTTTTTCCTGCCTCAATATCTTGA

TATGTTATGTTTACTCCCAATCTCCCATTTTTACCACTAAAATTCTCCAACTTTCATAAACTTTTTTTTG

GAAAAATTTCCATTGTATCAGCCCCTGACAGAAAAAGGATCTCTGAGCCTAAAGGAGGAAAAGTCCCACC

AACTACCAGACCAGAACACGAGCCCCTCTGGGCAGCAGGATTCCTAAGTCAAAGACCAGTTTGACCCAAA

CTGGCCTTTTAAAATAATCAGGAGTGACAGAGTCAACTTCTGCAGCACCTGCTTCTCCCCCACTGTCCCT

TCCATCTTGGAATGTGTCTAAAAAAGCATAGCTGCCCTTTGCTGTCCTCAGAGTGCATTTCCTGGAGACG

GCAGGCTTAGGTCTCACTGACAGCATGCCAGACACAACTGAATCGAAGCAGGCCTGAAGCCTAGGTCAGG

GTTTCAGGAGTCCAGCCCCAGGAGGCAAAGTCACCAATGCAGGGAGGTAAATGCCTTTTGGCAGGAAAAC

CAATAGAGTTGGTTGGGTGGGGAGTCAGGGGTGGGAGGAGAAGGAGGAAGAGGAGGAAGGCCAGACTGGC

CTGCCCTTTCTCCCATACTTCACCCCAGCAGAGGTTCATGGGACACAGTTGGAAAGCCACTGGGAGGAAA

TGCCTCACTACAGGGGGGCCTCCTGTAGCAAGCCCAGCCGGTAATCCTCCTAATGAACCCACAAGGTCAA

TTCACAACTGATATCTTAGCTATTAAAGAAGTACTGACTTTACCAAAAGAATCATCAAGAAAGCTATTTA

TATAAACCCCCTCAGTCATTTTGAAATAAAATTAATTTTACAA

NOV17t, 13381678 SNP for SEQ ID NO: 842 aa SNP: Thr to Met at position

CG52643-02 278 757

Protein Sequence

MKPGGF LHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKF CSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDT CTMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLK QDL DEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPP II KRNGLTLNFLDLEDINDFGEDDSLYIT VTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPES QAQEPGVAASLRCHAEGIPMPRIT L NGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEV GVDEDISSLFIEDSARKTLANILWRΞEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIF SYEEI CPQREKNATQPCQ VSAVNVRNRYIYVAQPALSRVLVVOIQAQKVLQSIGVDPLPAFiSYDKSHDQVWVL SWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETM MPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGR FIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALBMEPDLLFLELSTG KVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWV GEV

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 17B.

Table 17B. Comparison of the NO V17 protein sequences.

N0V17a

N0V17b

N0V17c

N0V17d LEMKPGGFWLHLTLLGASLPAALG MDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSH

N0V17e

N0V17f

NOV17g

NOV17h NOV17i

NOV17J

NOV17k

NOV171

NOV17

NOVl7n

NOV17o '

NOV17p

NOV17q

NOV17a

NOV17b

NOV17c

NOV17d NELLASCGKKFCSRGSRCVLSRKTGEPECLGKRITVIHSKDCFLKGDTCTMAGYARLKNV

NOV17e

NOV17f

NOV17g

NOV17h

NOV17i

NOV17J

NOV17k

NOV171

NOVl7m

NOV17n

NOV17o

NOV17p

NOV17q

NOV17a

NOV17b ^:

NOV17c

NOV17d LLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDE

NOV17e

NOV17f

NOV17g

NOV17h

NOV17i

NOV17J

NOV17k

NOV171

NOV17m

NOV17n

NOV17o

NOV17p

NOV17q

NOV17a MKPGGF LHLTL

NOV17b LEMKPGGF LHLTL

NOV17c LEMKPGGFWLHLTL

NOV17d DLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCA

NOV17e

NOV17f —LEMKPGGFWLHLTL

NOV17g MKPGGFWLHLTL

NOV17h -TGSTMKPGGFWLHLTL

NOV17i LEGLSTVLTCA

NOV17J LEGLSTVLTCA

NOV17k LEGLSTVLTCA NOV171

NOV17m

NOV17n

NOV17o

NOV17p MKPGGFWLHLTL

NOV17q

NOVl7a LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17b LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17c LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOVl7d VHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQ NOVl7e LEWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOVl7f LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOVl7g LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOVl7h LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOVl7i VHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQ NOVl7j VHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQ NOVl7k VHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQ NOVl71 -YLRFAFTGSWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOVl7m TGSWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOVl7n NOVl7o WMDPGTSRGPDVGVEESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17p LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOVl7q WMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR

NOVl7a GSRCVLSRKTGEP ECQCLEACRPSYVPVCGSDGRFYENHCKL NOVl7b GSRCVLSRKTGEP ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17c GSRCVLSRKTGEP ECQCLEACRPSYVPVCGSDGRFYENHCKL NOVl7d THVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSL NOVl7e GSRCVLSRKTGEP ECQCLEACRPSYVPVCGSDGRFYENHCKL NOVl7f GSRCVLSRKTGEP ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17g GSRCVLSRKTGEP ECQCLEACRPSYVPVCGSDGRFYENHCKL NOVl7h GSRCVLSRKTGEP ECQCLEACRPSYVPVCGSDGRFYENHCKL NOVl7i THVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSL NOV17J THVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSL NOVl7k THVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSL NOV171 GSRCVLSRKTGEP ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17m GSRCVLSRKTGEP ECQCLEACRPSYVPVCGSDGRFYENHCKL NOVl7n NOVl7o -GSRCVLSRKTGEP- -ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17p -GSRCVLSRKTGEP- -ECQCLEACRPSYVPVCGSDGRFYENHCKL NOVl7q -GSRCVLSRKTGEP- -ECQCLEACRPSYVPVCGSDGRFYENHCKL

NOVl7a HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ- NOVl7b HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ- NOVl7c HRAACLLGKRITVIHSKDCFLKGDTCTIAGYARLKNVLLALQTRLQPLQ EGDSRQ- NOV17d LANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREE NOVl7e HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ- NOV17f HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ- NOVl7g HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ- NOVl7h HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ- NOV17i LANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEDASTW NOV17J LANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTR NOVl7k LANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREE NOVl71 HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ- NOV17m HR_AACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ- NOV17n M_AGYARLKNVLLALQTRLQPLQ EGDSRQ- NOV17o HRAACLLGKRIAVIHSKDCFLKGDTCTMGGYARLKNVLLALQTRLQPLQ EGDSRQ-

NOV17p HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ-

NOV17q HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ EGDSRQ-

NOV17a DPASQK R LLVESLFRDLDAD— GNGHLSSSELAQHVL

NOV17b DPASQK R LLVESLFRDLDAD- GNGHLSSSELAQHVL

N0V17c DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

N0V17d GLSVGNMFYVFSDDGIIVIHPVDCEIQRHLK

N0V17e DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

N0V17f DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

N0V17g DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

N0V17h DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

N0V17i PVSCVFNAACDPAQGPTAWRACPFHLLLPGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLK

N0V17J LSVGNMFYVFSDDGIIVIHPVDCEIQRHLK

N0V17k GLSVGNMFYVFSDDGIIVIHPVDCEIQRHLK

N0V171 DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

NOVl7m DPASQK R LLVESLFRDLDAD GNGHLSSSELAQHVL

NOV17n DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

NOV17o DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

NOV17p DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

NOV17q DPASQK R LLVESLFRDLDAD—GNGHLSSSELAQHVL

NOV17a KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17b KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17c KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT

NOV17d PTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLWDIQAQKVLQS

NOV17e KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17f KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17g KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17h KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17i PTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQS

NOV17J PTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQS

NOV17k PTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQS

NOV171 KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17m KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRASVTTVT

NOV17n KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17o KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT

NOV17p KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17q KKQDLDEDLLGCSP GDLLRFDDYNSDSSLTLREFYMAFQWQLSLAPEDRVSVTTVT

NOV17a VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17b VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17C VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17d IGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFF

NOV17e VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17f VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17g VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17h VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17i IGVDPLPAKLSYGKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFF

NOV17J IGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFF

NOV17k IGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFF

NOV171 VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGED

NOV17m VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17n VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17o VGLSTVPTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINGR

NOV17p VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT

NOV17q VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17a CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17b CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17c CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOVl7d IPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFF

NOV17e CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17f CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17g CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17h CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17i IPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFF

NOVl7j IPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFF

NOV17k IPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFF

NOV171

NOV17m CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17n CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17o

NOV17p CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17q CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD

NOV17a VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN

NOV17b VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN

NOV17c VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTRLS

NOV17d IQCRQDSPASAARQLLVDSVTDSVLG

NOV17e VSTQMSKQLSLLANGSE

NOV17f VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN

NOV17g VSTQMSKQLSLLANGSE

NOV17h VSTQMSKQLSLLANGSE

NOV17i IQCRQDSPASAARQLLVDSVTDSVLG

NOV17J IQCRQDSPASAARQLLVDSVTDSVLG

NOV17k IQCRQDSPASAARQLLVDSVTDSVLG

NOV171

NOV17m VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN

NOV17n VSTQMSKQLSLLANGSE

NOV17o

NOV17p VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN

NOV17q VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN

NOV17a ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP

NOV17b ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP

NOV17C VGNMFYVFS DDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP

NOV17d

NOV17e

NOV17f ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP

NOV17g

NOV17h

NOV17i

NOV17J

NOV17k

NOV171

NOV17m ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP

NOV17n

NOV17o

NOV17p ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP

NOV17q ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP

NOV17a CQWVSAVNVRNRYIYVAQPALSRVLWDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS

NOV17b CQWVSAVNVRNRYIYVAQPALSRVLWDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS NOV17c CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS

NOV17d

NOV17e

NOV17f CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS

NOV17g

NOV17h

NOV17i

NOV17J

NOV17k

NOV171

NOV17m CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS

NOV17n

NOV17o

NOV17p CQWVSAVNVRNRYIYVAQPALSRVLWDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS

NOV17q CQWVSAVNVRNRYIYVAQPALSRVLWDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS

NOV17a WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA

NOV17b WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA

N0V17c WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA

N0V17d

N0V17e

N0V17f WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA

N0V17g

N0V17h

N0V17i

N0V17J

N0V17k

N0V171

N0V17m WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA

N0V17n

N0V17o

N0V17p WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA

N0V17q WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA

NOVl7a VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS

NOV17b VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS

NOVl7c VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS

NOV17d

NOV17e

NOVl7f VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS

NOV17g

NOV17h

NOV17i

NOV17J

NOV17k

NOV171

NOV17m VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS

NOV17n

NOV17o

NOV17p VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS

NOV17q VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS

NOV17a VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV17b VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV17C VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV17d PNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV17e NOV17f VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV17g

NOV17h

NOV17i PNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV17J PNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV17k PNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV171

NOV17m VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV17n

NOV17o

NOV17p VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

NOV17q VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ

RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL RSFTESNQYNIYAALHMEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL RSFTESNQYNIYAALHMEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL LHI_SSV_RY

RSFTESNQYNIYAALHMEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL LHI_SSVRY LHI_SSVRY

RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL

RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL LHI_SSVRY

RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPRGGTHRIMRDSGL

FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEV

FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEVLE

FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTWWVGEVLE

EDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVI

FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEVLE

EDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVI EDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVI

FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTWWLE

FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWLE DSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIR

FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTWWVGEVEFG

EDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGTKLHCFASCL QNTLRCEVSGIKGGTTVVWVGEV

FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEV

FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEV N0V17i

N0V17J

NOV17 k

N0V171 VYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVR

N0V17m

N0V17n

NOV17 o

NOV17p

NOV17 q

N0V17a

NOV17b

N0V17 c

N0V17d

N0V17e WDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHL

N0V17 f

N0V17g WDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHL

N0V17h VVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHL

N0V17i

N0V17J

N0V17k

N0V171 YEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIV

N0V17m

N0V17n

N0V17o

N0V17p

N0V17q

N0V17a

N0V17b

N0V17c

N0V17d '

N0V17e IRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPTVHKVDLETMMPLKTIGLHHHGCVPQ

NOV17f

NOV17g IRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQ

N0V17h IRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQ

N0V17i

N0V17J

N0V17k

N0V171 IHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRV

N0V17m

NOVl7n

NOV17o

NOV17p

NOVl7q

N0V17a

N0V17b

NOV17c

N0V17d

NOVl7e AMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAA

NOVl7f

NOV17g AMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAA

N0V17h AMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAA

NOV17i

NOV17J

NOV17k NOV171 LVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQH

NOV17m

NOV17n

NOV17o

NOV17p

NOV17q

NOVl7a NOV17b NOV17c NOV17d NOVl7e ADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLE NOVl7f NOVl7g ADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLE NOVl7h ADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLE NOV171 NOVl7j NOVl7k NOVl71 LIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVP

NOV17m

NOV17n

NOV17o

NOV17p

NOV17q

NOV17a

NOV17b

NOV17c

NOV17d

NOV17e LSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRC

NOV17f

NOV17g LSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRC

NOV17h LSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRC

NOV17i

NOV17J

NOV17k

NOV171 QAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSA

NOV17m

NOV17n

NOV17o

NOV17p

NOV17q

NOV17a

NOV17b

NOV17c

NOV17d

NOV17e EVSGIKGGTTWWVGEVLE

NOV17f

NOV17g EVSGIKGGTTWWVGEV

NOV17h EVSGIKGGTTWWVGEVEFG-

NOV17i

NOV17J

NOV17k

NOV171 AADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFL

NOV17m

NOV17n NOVl7o

NOV17p NOVl7q

NOVl7a NOV17b

NOVl7c NOVl7d

NOVl7e NOV17f

NOVl7g

NOV17h NOVl7i NOVl7j NOVl7k

NOVl71 ELSTGKVGMLKNLKEPPAGPAQPRGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLR

NOVl7m

NOV17n

NOVl7o

NOV17p NOVl7q

NOVl7a NOVl7b

NOVl7c NOVl7d NOVl7e NOVl7f NOVl7g

NOV17h NOVl7i NOVl7j

NOVl7k NOVl71 CEVSGIKGGTTVVWVGEVEFG

NOV17m NOVl7n NOVl7o NOV17p

NOVl7q

NOVl7a (SEQ ID NO 240)

NOVl7b ('SEQ ID NO 242)

NOVl7c (SEQ ID NO 244)

NOVl7d (SEQ ID NO 246)

NOVl7e (SEQ ID NO 248)

NOVl7f (SEQ ID NO 250)

NOVl7g (SEQ ID NO 252)

NOV17h (SEQ ID NO 254)

NOVl7i (SEQ ID NO 256)

NOVl7j (SEQ ID NO 258)

NOV17k (SEQ ID NO 260)

NOVl71 (SEQ ID NO ^• 262)

NOVl7m (SEQ ID NO . 264)

NOV17n (SEQ ID NO . 266)

NOVl7o (SEQ ID NO 268)

NOV17p (SEQ ID NO 270)

NOVl7q (SEQ ID NO : 272) Further analysis of the NOVl 7a protein yielded the following properties shown in Table 17C.

Table 17C. Protein Sequence Properties NOVl 7a

SignalP analysis: j Cleavage site between residues 23 and 24

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 2; pos.chg 1; neg.chg 0 H-region: length 22; peak value 8.15 PSG score: 3.75

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 2.14 possible cleavage site: between 22 and 23

>» Seems to have a cleavable signal peptide (1 to 22)

ALOM: Klein et al's method for TM region allocation Init position for calculation: 23

Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 3.39 (at 513) ALOM score: -0.27 (number of TMSs : 0)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 11 Charge difference: -4.5 C(-2.0) - N( 2.5) N >= C: N-terminal side will be inside

MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.60 Hyd Moment (95) : 5.25 G content: 4 D/E content: 1 S/T content: 2 Score: -6.75

NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 9.1% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals : none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 76.7

COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23) :

33.3 %: extracellular, including cell wall

22.2 %: vacuolar

22.2 %: mitochondrial

22.2 %: endoplasmic reticulum

» prediction for CG52643-02 is exc (k=9)

A search of the NOVl 7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D.

In a BLAST search of public sequence databases, the NOVl 7a protein was found to have homology to the proteins shown in the BLASTP data in Table 17E.

PFam analysis predicts that the NOVl 7a protein contains the domains shown in the Table 17F.

Example 18.

The NOVl 8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 18 A.

Table 18A. NOV18 Sequence Analysis

NOVl 8a, CG53270-01 SEQ ID NO: 279 1140 bp DNA Sequence ORF Start: ATG at 21 ORF Stop: TGA at 1122

CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATA

AATTTAGGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGC GATCAAGATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTG AGATTCTGGCCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGC AAGGTCTACATCGTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGC CCTGCATGAGGACGAAGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACC TGGACGTCGTCCACCGGGACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTG TCCGACTTCAGCTTCTCCAAGCGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTT CTGTGGGTCACCAGCGTATGCGGCCCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACG ACATCTGGAGCCTAGGCGTGATCCTCTACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAAC ATCAAGAAGATGCTGCGTATCCAGAAGGAGCACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGG CGAGTGCAAGGACCTCATCTACCACATGCTGCAGCCCGACGTCAACCGGCGGCTCCACATCGACGAGA TCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGGGATCTCCCTCTGTGGCCATCAACAAGGAGGGG GAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAACCTGGCTCTGACAAGAAGTCTGCCACCAA GCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGAGACAAAACCCGAGGGGACAGCAATGC AAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGTCGACTATGGAGACAGAGGAAGGG CCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGCCCAG

NOV18a, CG53270-01 SEQ ID NO: 280 367 aa MW at 41617.4kD Protein Sequence

MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAI IIDRKKAPADFLEKFLPREIEILAMLN HCSIIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDWHRD LKCDNLLLDEX1FNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQP VYDI SLGV ILYIMVCGSMPYDDSNIK^ LRIQEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWM QPKARGSPSVAIN EGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSE ILGFPS PSTMETEEGPPQQPPETRAQ

NOVl 8b, 274089779 SEQ ID NO: 281 802 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence

CACCGGATCCTACCTCCTGGGGATAAATTTAGGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACT CTGAGCGCCTGAAGTTCAATGTGGCGATCAAGATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTG GAGAAATTCCTTCCCCGGGAAATTGAGATTCTGGCCATGTTAAACCACTGCTCCATCATTAAGACCTA CGAGATCTTTGAGACATCACATGGCAAGGTCTACATCGTCATGGAGCTCGCGGTCCAGGGCGACCTCC TCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGAAGCTCGCAAGAAGTTCCACCAGCTTTCC TTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGGACCTCAAGTGTGACAACCTTCTCCT TGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAGCGCTGCCTGCGGGATGACAGTG GTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGCCCCAGAGGTGCTGCAGGGC ATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCTACATCATGGTCTGCGG CTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAGCACCGCGTCAACT TCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCAGCCCGACGTC AACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGGGTACCGGC

NOVl 8b, 274089779 SEQ ID NO: 282 267 aa MW at 30670.4kD Protein Sequence

TGSYLLGINLGEGSYAKV SAYSERLKF VAIKIIDR KAPADFLEKFLPREIEILAML HCSII TY EIFETSHG VYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAI YCHDLDVVHRDLKCDNLLL DKDFNIKLSDFSFSKRCLPJ3DSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDI SLGVILYI VCG SMPYDDSNI K LRIQ EHRVNFPRSKHLTGECKDLIYHMLQPDVMRRLHIDEILSHCWMGTG NOVlδc, CG53270-02 SEQ ID NO: 283 1132 bp DNA Sequence ORF Start: ATG at 15 ORF Stop: TGA at 1116

GCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAATTTA

GGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTC TGGCCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTC TACATCGTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCA TGAGGACGAAGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACG TCGTCCACCGGGACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGAC TTCAGCTTCTCCAAGCGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGG GTCACCAGCGTATGCGGCCCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCT GGAGCCTAGGCGTGATCCTCTACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAG AAGATGCTGCGTATCCAGAAGGAGCACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTG CAAGGACCTCATCTACCACATGCTGCAGCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCA GCCACTGCTGGATGCAGCCCAAGGCACGGGGATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGT TCCCGGGGAACTGAACCCTTGTGGACCCCCGAACCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGA GCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGAGACAAAACCCGAGGGGACAGCAATGCAAATGT CCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGTCGACTATGGAGACAGAGGAAGGGCCCCCC CAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGCCC

NOV18c, CG53270-02 SEQ ID NO: 284 367 aa MW at 41617.4kD Protein Sequence

MDDAAVLKRRGYLLGINLGEGSYA VKSAYSERLKFNVAI IIDRKKAPADFLEKFLPREIEILAMLN HCSIIKTYEIFETSHGKVYIVMEIAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRD LKCDNLLLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDI SLGV ILYIMVCGSMPYDDSNIKIv^LRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWM QPKARGSPSVAINKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQ.SE ILGFPSKPSTMETEEGPPQQPPETRAQ

NOV18d, 13382344 SNP for SEQ ID NO: 1140 bp SNP: 89 T/C

CG53270-01 285

DNA Sequence ORF Start: ORF Stop: end of sequence ATG at 21

CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT

TTAGGAGAGGGCTCCTACGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGG CCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATC GTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGA AGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGG ACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAG CGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGC CCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCT ACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAG CACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCA GCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGG GATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAA CCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGA GACAAAACCCGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGT CGACTATGGAGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGC CCAG

NOV18d, 13382344 SNP SEQ ID NO: 367 aa SNP: no change in protein for 286 sequence

CG53270-01

Protein Sequence

^mD V K G GI LGEGSY K KS SER KF AIKIID KKAPADF EKF PREIEILAMLNHCS IIKTYEIFETSHG VYIVMEIαAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRDLKCDNL LLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEE GPPQQPPETRAQ

NOV18e, 13382345 SNP for SEQ ID NO: 287 1140 bp SNP: 95 A/G

CG53270-01 ORF Start: ATG at 21 ORF Stop: TGA at 1122

DNA Sequence

CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT

TTAGGAGAGGGCTCCTATGCAAAGGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGG CCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATC GTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGA AGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGG ACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAG CGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGC CCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCT ACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAG CACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCA GCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGG GATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAA CCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGA GACAAAACCCGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGT CGACTATGGAGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGC CCAG

NOV18e, 13382345 SNP SEQ ID NO: 367 aa SNP: no change in protein for 288 sequence

CG53270-01

Protein Sequence

MDDAAVLKKRGYLLGIlsπ^GEGSYAi^^SAYSERLKFNVAIKIIDRKKAPADFLEKFLPREIEILAMLNHCS IIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDWHRDLKCDNL LLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEE GPPQQPPETRAQ

NOV18f, 13376391 SNP for SEQ ID NO: 289 1140 bp SNP: 310 A G

CG53270-01 ORF Start: ATG at 21 ORF Stop: TGA at 1122

DNA Sequence

CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT

TTAGGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGG CCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATC GTCATGGAGCTCGCGGTCCAGGGCGGCCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGA AGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGG ACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAG CGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGC CCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCT ACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAG CACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCA GCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGG GATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAA CCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGA GACAAAACCCGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGT CGACTATGGAGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGC CCAG

|NOV18f, 13376391 SNP for SEO ID NO: 367 aa SNP: Asp to Gly at position 97 CG53270-01 290 Protein Sequence

MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPREIEILAMLNHCS IIKTYEIFETSHGKVYIVMELAVQGGLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRDLKCDNL LLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPΞTKPEGTAMQMSRQSEILGFPSKPST ETEE GPPQQPPETRAQ

NOV18g, 13376390 SNP for SEQ ID NO: 291 1140 bp SNP: 978 C/T

CG53270-01 ORF Start: ATG at 21 ORF Stop: TGA at 1122

DNA Sequence

CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT

TTAGGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGG CCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATC GTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGA AGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGG ACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAG CGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGC CCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCT ACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAG CACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCA GCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGG GATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAA CCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGTCCCAGGCACAGCCTGA GACAAAACCCGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGT CGACTATGGAGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGC CCAG

NOV18g, 13376390 SNP for SEQ ID NO: 367 aa SNP: Pro to Ser at position 320 CG53270-01 1292

Protein Sequence roD LKERGY LGI LGEGSYA VKSAYSER Fl r AIKIIDRK AP DF E F PREIEI AM HCS IIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRDLKCDNL LLDIΦFNIKLSDFSFSIO^CLRDDSGP ^-^SKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQSQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEE GPPQQPPETRAQ

NOV18h, 13376389 SNP for SEQ ID NO: 293 1140 bp SNP: 996 A/G

CG53270-01 ORF Start: ATG at 21 ORF Stop: TGA at 1122

DNA Sequence

CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT

TTAGGAGAG

GGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAAGATCATCGA

CCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGGCCATGTTAA

ACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATCGTCATGGAG

CTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGAAGCTCGCAA

GAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGGACCTCAAGT

GTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAGCGCTGCCTG

CGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGCCCCAGAGGT

GCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCTACATCATGG

TCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAGCACCGCGTC

AACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCAGCCCGACGT

CAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGGGATCTCCCT

CTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAACCTGGCTCT

GACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGAGGCAAAACC CGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGTCGACTATGG AGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGCCCAG

NOV18h, 13376389 SNP for SEQ ID NO: 367 aa SNP: Thr to Ala at position 326

CG53270-01 294

Protein Sequence

MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPREIEILAMLNHCS IIKTYEIFETSHG VYIV ELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRDLKCDNL LLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGΞSSRGTEPL TPEPGSDKKSATKLEPEGEAQPQAQPEAKPEGTAMQMSRQSEILGFPSKPSTMETEE GPPQQPPETRAQ

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 18B.

Table 18B. Comparison of the NOV18 protein sequences.

NOVlδa MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPRE

NOV18b TGSYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPRE

NOV18C MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPRE

NOV18a IEILAMLNHCSIIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQL

NOVl8b IEILAMLNHCSIIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQL

NOV18C IEILAMLNHCSIIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQL

NOV18a SLAIKYCHDLDWHRDLKCDNLLLD DFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPA

NOVl8b SLAIKYCHDLDVVHRDLKCDNLLLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPA

NOV18c SLAIKYCHDLDVVHRDLKCDNLLLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPA

NOVl8a YAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGSMPYDDSNIKKMLRIQKEHRVNFPRSKH NOVl8b YAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGSMPYDDSNIKKMLR1QKEHRVNFPRSKH NOVl8c YAAPEVLQGIPYQPKVYD1 SLGVILYIMVCGSMPYDDSNIKKMLRIQKEHRVNFPRSKH

NOVl8a LTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAINKEGESSRGTEPLWTP NOVl8b LTGECKDLIYHMLQPDVNRRLHIDEILSHC MGTG NOVl8c LTGECKDLIYHMLQPDVNRRLHIDEILSHCW QPKARGSPSVAINKEGESSRGTEPL TP

NOVl8a EPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSE1LGFPSKPSTMETEEGPPQQ NOVl8b NOVl8c EPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEEGPPQQ

NOVl8a PPETRAQ

NOVl8b

NOVl8c PPETRAQ

NOVl8a (SEQ ID NO: 280)

NOVl8b (SEQ ID NO: 282)

NOVl8c (SEQ ID NO: 284)

Further analysis of the NOVl 8a protein yielded the following properties shown in Table 18C. Table 18C. Protein Sequence Properties NOV18a

SignalP analysis: No Known Signal Sequence Predicted

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 10; pos.chg 3; neg.chg 2 H-region: length 9; peak value 4.19 PSG score: -0.21

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.57 possible cleavage site: between 24 and 25

>» Seems to have no N-terminal signal peptide

Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 1.11 (at 86) ALOM score: -1.44 (number of TMSs: 0)

MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75): 8.48 Hyd Moment ( 95 ) : 7.98 G content: 0 D/E content: 2 S/T content: 0 Score: -6.50

NUCDISC: discrimination of nuclear localization signals pat4 : none pat7 : none bipartite: none content of basic residues: 14.2% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals: none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

Tyrosines in the tail: none

Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE riboso al protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none

COIL: Lupas 's algorithm to detect coiled-coil regions total: 0 residues

.esialt :s (k = 9/23) :

60. .9 % : nuclear

17..4 % : cytoplasmic

13..0 % : peroxisomal

8..7 % : mitochondrial

» prediction for CG53270-01 is nuc (k=23)

A search of the NOVl 8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18D.

In a BLAST search of public sequence databases, the NOVl 8a protein was found to have homology to the proteins shown in the BLASTP data in Table 18E.

PFam analysis predicts that the NOVl 8a protein contains the domains shown in the Table 18F.

Table 18F. Domain Analysis of NOV18a

Identities/

Pfam Domain NO V18a Match Region j Similarities | Expect Value for the Matched Region pkinase 12..272 94/304 (31%) 5.5e-73 204/304 (67%)

Example 19.

The NOVl 9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 19 A.

Table 19A. NOV19 Sequence Analysis

NOV19a, CG54254-04 SEQ ID NO: 295 2040 bp

DNA Sequence ]θRF Start: ATG at 1 ORF Stop: TGA at 2023

ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGT GATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGA CGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAAC GACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAA CCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTAT ACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGAC AACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGA TGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGC TCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGG CTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCT GGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACC TCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTG CAGAAACTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGA GCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGG GGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGG GACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGT CCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCG GCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCC CTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGC CACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCA CGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCC GTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCC CAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGACAC CCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAAC GCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTT CCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCT ACAACCGGGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTG GAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGT CCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCA CGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCCGCCCACCCGG

NOVl 9a, CG54254-04 SEQ ID NO: 296 674 aa MW at 74087.4kD Protein Sequence

MVVAHPTATATTTPTATVTATVVMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN DRGLTSIPADIPDDATTLYLQNNQI NAGIPQDLKTKV VQVIYLYENDLDEFPINLPRSLRELHLQD MN^TIAP DSL-J^IPLLΞKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSR HLSSIPSGLPHTLEELR LDDIMISTIPLHAFKGLNSLRRLVLDGNLLA QRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHL QKLYLQDNAI SHI PYNTIIAKMRELERLDLSNNNLTTLPRGLFDDLGNIAQLLLRNNP FCGCNLM LR DWVKARAAVVLSJVRGLMCQGPEK GMAIKDITSEMDECFETGPQGGVA AAAKTTASNHASATTPQGS LFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRIT KATLPASSFRLS LRLGHSPA VGSITETLVQGDKTEYLLTALEPKSTYIICIVΓVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQN AGPMASLPLAGIIGGAVALVFLFLVLGAICIWYVHQAGELLTRERAY RGSREKDDYMESGTKKDNSIL EIRGPGLQ LPINPYRAKEEYWHTIFPSNGSSLC ATHTIGYGTTRGYRDGGIPDIDYSYT

NOV19b, 247846813 SEQ ID NO: 297 1933 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence

AGGCTCCGCGGCCGCCCCCTTCACCGGATCCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCG ACAACGGCTTCATCTACTGCAACGACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCC ACCACCCTCTACCTGCAGAACAACCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGT CAACGTGCAGGTCATCTACCTATACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCC TCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCG CTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGC CGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGC CGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAG GGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGA CACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCC TCAACCTGCCCAGCGCCCACCTGCAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTAC AACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCC CCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTG GCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTC ATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTG TTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCT CTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGAC TCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCT GACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGC TGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAG TACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAA TGCCTACGTAGCTGATGAGACACCTGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCA CCACACTCAACCAGGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGG GCAGTGGCTCTGGTCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGA GCTGCTGACCCGGGAGAGGGCCTACAACCGGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGA CCAAGAAGGATAACTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTAC CGCGCCAAAGAGGAGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCAC ACACACCATTGGCTATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCT ACACACTCGAGGGCAAGGGTGGGCGCGCC

NO VI 9b, 247846813 SEQ ID NO: 298 644 aa MW at 70572.3kD Protein Sequence

GSAAAPFTGSIDSTTCPSVCRCDNGFIYCNDRGLTSIPADIPDDATTLYLQN QI NAGIPQDLKTKV NVQVIYLYENDLDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLE LHLDDNSVSTVSIEEDAFA DSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRIS IPLHAFKGLNS RRLVLDGNLLANQRIADD TFSRLQNLTELSLVR SLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELERLDLSN NLTTLP RGLFDDLGNLAQLLLRN PWFCGCNLM LRD VKARAAVVNVRGLMCQGPEKVRGMAIKDITSEMDEC FETGPQGGVANAAA TTASNHASATTPQGSLFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKAL TADSIRIT KATLPASSFRLS LRLGHSPAVGSITETLVQGDKTEYLLTALEPKSTYIIC VT ETSN AYVADETPVCAKAΞTADSYGPTTTLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAIC YVHQAGE LLTRERAYNRGSRKKDDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKAT HTIGYGTTRGYRDGGIPDIDYSYTLEGKGGRA

NOVl 9c, 247846825 SEQ ID NO: 299 785 bp

DNA Sequence ORF Start: at 2 ORF Stop: 784

AGGCTCCGCGGCCGCCCCCTTCACCGGATCCGACGCCACCACCCTCTATCTGCAGAACAACCAGATCA ACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAAT GACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGT GCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACT CCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTG AGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGA CAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGG ACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAG CTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACT CTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGC GGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGCTCGAG GGCAAGGGTGGGCGCGCCGACCCAGCTTTCTTGTACA

NOV19c, 247846825 SEQ ID NO: 300 261 aa MW at 29146.5kD Protein Sequence GSAAAPFTGSDATTLYLQMIsTQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQDNNV RTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDD :NRISTIPLi FKGLNSLRRLVLDGls iANQRIADDTFSRLQiπ_JTELSLVPJsISIJ^.PPLNLPSAHLQKL YLQDNAISHIPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGLEGKGGRADPAFLY

NOVl 9d, 247846967 SEQ ID NO: 301 1880 bp DNA Sequence

ORF Start: at 2 ORF Stop: 1879

AGGCTCCGCGGCCGCCCCCTTCACCGGATCCGACGCCACCACCCTCTATCTGCAGAACAACCAGATCA ACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAAT GACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGT GCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACT CCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTG AGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGA CAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGG ACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAG CTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAGCT CTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGC GGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTG GCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGT GAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCA TGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCC AATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCCCTGTTTAC CCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTG ATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAG GCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTC CATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCA CCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGACACCCGTGTGT GCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACGCTGGCCC CATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTTCCTGGTCC TGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCTACAACCGG GGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGAAATCCG CGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACACTA TCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCACGCGGGGC TACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACACTCGAGGGCAAGGGTGGGCGCCCCGA CCCAGCTTTCTTGTACACAGCTGGCATTATAAGAAGCCATTGCT

NOV19d, 247846967 SEQ ID NO: 302 626 aa MW at 68699.3kD Protein Sequence

GSAAAPFTGSDATTLYLQNNQILRØAGIPQDLKTKVLSWQVIYLYENDLDEFPINLPRSLRELHLQDN V RTIARDSLARIPLLE LHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDD RISTIPLHAFKGLNSLRRLVLDGNLIJ^QRIADDTFSRLQΪΓLTELSLVR SLAAPPLNLPSAHLQKL YLQDNAISHIPYNTLAKI^ELERLDLSNLNLNLTTLPRGLFDDLG LAQLLLR NP FCGCLSRLM LRD V ARAAVV VRGLMCQGPEKVRGMAIIODITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFT LKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAVGS ITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGP ASLPIΛGIIGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSRK DDYMESGTK DNSILEIR GPGLQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYTLEG GGRPD PAFLYTAGIIRSHC

NOV19e, 283841186 JSEQ ID NO: 303 2041 bp

DNA Sequence JORF Start: at 2 JORF Stop: end of sequence

CACCGGATCCATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGG CCACCGTTGTGATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATC GCCTTCCTGACGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCAT CTACTGCAACGACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTACC TGCAGAACAACCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTC ATCTACCTATACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCA CCTGCAGGACAACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGC jTGCACCTGGATGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAG CTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGA _|GGAGCTGCGGCTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCC iTGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGC CTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAG CGCCCACCTGCAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCA AGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTC GACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCAT GTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCC CTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGG CCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCC CCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACT ACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCC ATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCA CAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAG CCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCT GATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCA GGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGG TCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGG GAGAGGGCCTACAACCGGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAA CTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGG AGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGC TATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACACTCGAGGG C

NOV19e, 283841186 [SEQ ID NO: 304 680 aa MW at 74631. lkD Protein Sequence

TGSMVVAHPTATATTTPTATVTATVVMTTAT DLRD LFLCYGLIAFLTEVIDSTTCPSVCRCDNGFI YCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRS RELH LQDlsraVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLE ΞLRLDDNRISTIPLHAFKGIJSISLRRLVLDGNLlJ^QRIADDTFSRLQNLTELSLVRNSIjAAPPL LPS AHLQKLYLQDNAISHIPYNTliAKMRELERLDLSMSINLTTLPRGLFDDLGNLAQLLLR NP FCGCNLM LRDVWKARAAVVNVRGL CQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTP QGSLFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRIT KATLPASSFRLS LRLGH SPAVGSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQ EQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKKDDY ESGTKDN SILEIRGPGLQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYTLEG

|NOV19f, CG54254-01 SEQ ID NO: 305 2025 bp

DNA Sequence JORF Start: ATG at 1 ORF Stop: TGA at 2023

ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGT GATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGA CGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAAC GACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGATGCCACCACCCTCTACCTGCAGAACAA CCAGATCAACAACGCCGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTAT ACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGAC AACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGA TGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGC TCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGG CTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCT GGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACC TCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTG CAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGA GCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGG GGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGG GACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGT CCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCG GCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCC CTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGC CACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCA CGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCC GTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCC CAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGACAC CCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAAC GCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTT CCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCT ACAACCGGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTG GAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGT CCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTACGGCACCA CGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATGA

NOV19f, CG54254-01 SEQ ID NO: 306 674 aa MW at 74086.5kD Protein Sequence VVAHPTATATTTPTATVTATVVMTTAT DLRD LFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN DRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQD NNVRTIARDSIARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELR LDD R1STIPLHAFKGLNSLRRLVLDG LLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHL QKLYLQDNAI SHI PYNTIJA MRELERLDLSNNNLTTLPRGLFDDLGNIJAQLLLRNNP FCGC LM LR D VKARAAVVNV11GLMCQGPEKVKG AIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGS FTLKAKRPGLRLPDSNIDYPMATGDGA TLAIHVKALTADS IRITWKATLPAS SFRLS LRLGHS PA

VGSITETLVQGDKTEYLLTALEPKSTYIIC VT ETSNAYVADETPVCAKAETADSYGPTTTLNQEQN AGPMASLPIAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSR DDY ESGT KDNSIL EIRGPGLQMLPINPYRAKEEYWHTIFPSNGSSLC ATHTIGYGTTRGYRDGGIPDIDYSYT

|NOV19g, CG54254-02 SEQ ID NO: 307 1995 bp

DNA Sequence j₀RF Start: ATG at 1 JORF Stop: TGA at 1993

ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGT GATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGA CGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAAC GACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGATGCCACCACCCTCTACCTGCAGAACAA CCAGATCAACAACGCCGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTAT ACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGAC AACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGA TGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGC TCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGG CTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCT GGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACC TCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCTACCTGCAGGACAATGCCATC AGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAA CCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACA ACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTC AACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAG CGAGGTGGAGAGTGTTTTGAGACGGGCGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGG CCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGG CTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCAT CCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTT TCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAG GGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCAC CATGGAGACCAGCAATGCCTACGTAGCTGATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACA GCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCG GGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGT GCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCTACAACCGGGGCAGCAGGAAAAAGGATGACT ATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTG CCCATCAACCCGTACCGCGCCAAAGAAGAGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAG CCTCTGCAAGGCCACACACACCATTGGCTACGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCG jACATAGACTACTCCTACACATGA

NOV19g, CG54254-02 SEQ ID NO: 308 664 aa MW at 72982.3kD Protein Sequence iMWAHPTATATTTPTATVTATWMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN

DRGLTSIPADIPDDATTLYLQNNQI NAGIPQDLKTKV VQVIYLYE DLDEFPINLPRSLRELHLQD

NNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELR

LDDNRISTIPLHAFKGLNSLRRLVLDGNLLAMQRIADDTFSRLQNLTELSLVRNSLAAPPLYLQDNAI

SHIPYNTIAKMRELERLDLSNNNLTTLPRGLFDDLGNIiAQLLLR.^ VRGLMCQGPEKVRGMAI DITSEVESVLRRAPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRPG

LRLPDSNIDYPMATGDGA TLAIHVKALTADSIRIT KATLPASSFRLS LRLGHSPAVGSITETLVQ

GDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMASLPLA

GIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKKDDY ESGTKKDNSILEIRGPGLQML

PINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT

NOV19h, CG54254-03 SEQ ID NO: 309 1485 bp

DNA Sequence ORF Start: at 1 ORF Stop: end of sequence

ACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGACTCACATC CATCCCCGCAGATATCCCTGATGATGCCACCACCCTCTACCTGCAGAACAACCAGATCAACAACGCCG GCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGACCTGGAT GAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCAT TGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCA CCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAAC CACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCAT CTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACC TGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTG GTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAGCTCTACCTGCA GGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACC TGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTG CTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACG GGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCA AGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCT GCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGC CAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCA AGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTC CCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGA GACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCA TCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGACACCCGTGTGTGCCAAGGCA GAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACGCTGGC

NOV19h, CG54254-03 SEQ ID NO: 310 ^l 495 aa MW at 54572.3kD Protein Sequence

TTCPSVCRCDNGFIYC DRGLTSIPADIPDDATTLYLQNNQI AGIPQDLKTKVNVQVIYLYENDLD

EFPI LPRSLRELHLQD NVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQL LLFLSRN

HLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGL SLRRLVLDGNLLA QRIADDTFSRLQ LTELSL

VR SLAAPPL LPSAHLQKLYLQDNAISHIPY TLAKMRELERLDLSNNNLTTLPRGLFDDLGNLAQL

L Rl^mP FCGCN M RDi^KA AAVVNV GL CQGPEK RGIy-AIKDI SEm

AKTTASNHASATTPQGSLFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRIT KATL

PASSFRLS LRLGHSPAVGSITETLVQGDKTEYLLTALEPKSTYIIC VTMETSNAYVADETPVCA A

ETADSYGPTTTLNQEQNAG

NOV19i, CG54254-05 jSEQ ID NO: 311 |2041 bp DNA Sequence ORF Start: ATG at 11 ORF Stop: end of sequence

CACCGGATCCATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGG

CCACCGTTGTGATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATC GCCTTCCTGACGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCAT CTACTGCAACGACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTACC TGCAGAACAACCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTC

ATCTACCTATACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCA

CCTGCAGGACAACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGC

TGCACCTGGATGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAG

CTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGA

GGAGCTGCGGCTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCC

TGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGC

CTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAG

CGCCCACCTGCAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCA

AGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTC

GACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCAT

GTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCC

CTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGG

CCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCC

CCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACT

ACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCC

ATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCA

CAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAG

CCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCT

GATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCA

GGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGG

TCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGG

GAGAGGGCCTACAACCGGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAA

CTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGG

AGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGC

TATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACA

C

NOV19i, CG54254-05 SEQ ID NO: 312 674 aa MW at 74086.5kD Protein Sequence

MVVAHPTATATTTPTATVTATVVMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN

DRGLTSIPADIPDDATTLYLQNNQI NAGIPQDLKTKVNVQVI LYENDLDEFPINLPRSLRELHLQD

NNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADS QLKLLFLSRNHLSSIPSGLPHTLEELR

LDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHL

QKLYLQDNAISHIPY TIAIOymELERLDLSNNOTjTTLPRGLFDDLGNIAQLLLRIrøP FCGCNLMWLR

DWVKARAAVVNVRGLMCQGPEKVRGiAIiωiTSEIffiECFETGPQGGVANAAA TTASNHASATTPQG

LFTLKAKRPGLRLPDSNIDYPMATGDGA TLAIHVKALTADSIRIT KATLPASSFRLS LRLGHSPA

VGSITETLVQGDKTΞYLLTALEP STYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQN

AGPMASLPIAGIIGGAVALVFLFLVLGAICl^r QAGELLTRERAYl^GSRKJXDDYMESGTK DNSIL

EIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT

NOV19J, CG54254-06 SEQ ID NO: 313 2039 bp

DNA Sequence ORF Start: at 1 ORF Stop: TAG at 2020

ACCGCCACTGCCACCACTACGCCCACTGCCACTGTCACGGCCACCGTTGTGATGACCACGGCCACCAT GGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGAGGTCATCGACAGCA CCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGACTCACATCC ATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTACCTGCAGAACAACCAGATCAACAACGCCGG CATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGACCTGGATG AGTTCCCCATCAACCTGCCCCGCCCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATT GCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCAC CGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAACC ACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATC TCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCT GCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGG TGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAGCTCTACCTGCAG GACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCT GTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGC TGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGG GCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAA GGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTG CCAAGACCACGGCCAGCAACCACGCCACTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCC AAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAA GACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCC CCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGAG ACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCAT CTGCATGGTCACCATGGAGACCAGCAATGCCTATGTAGCTGATGAGACACCCGTGTGTGCCAAGGCAG AGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACGCTGGCCCCATGGCGAGC CTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTTCCTGGTCCTGGGGGCCAT CTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCTACAACCGGGGCAGCAGGA AAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGAAATCCGCGGCCCTGGG CTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACACTATCTTCCCCTC CAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTACGGCACCACGCGGGGCTACCGCCACT GCCACCACCTCCCCGACATAGACTACTCCTACACACGATCCCCGACATAGACTACTCCTACACATGA

NOV19j, CG54254-06 SEQ ID NO: 314 673 aa MW at 74202.6kD Protein Sequence

TATATTTPTATVTATVVMTTAT DLRD LFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCNDRGLTS

IPADIPDDATTLYLQN QI1SMAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRPLRELHLQDNNVRTI

ARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRI

STIPLHAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQ

DNAISHIPYNTIiAKMRELERLDLSMfcmLTTLPRGLFDDLGNI^QLLLRim^

AAVVNVRGLMCQGPEKVRGMAIKDITSE DECFETGPQGGVANAAA TTASNHATATTPQGSLFTLKA

KRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADS IRI TWKATLPAS S FRLS WLRLGHS PAVGS I E

TLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMAS

LPLAGI IGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSR KDDYMESGTKKDNS ILEIRGPG

LQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGTTRGYRHCHHLPDIDYSYTRSPT

NOVl 9k, CG54254-07 SEQ ID NO: 315 2049 bp

DNA Sequence ORF Start: ATG at 16 ORF Stop: TAG at 2038

CACCGCGGCCGCACCATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGT

CACGGCCACCGTTGTGATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGC TCATCGCCTTCCTGACGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGC TTCATCTACTGCAACGACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCT CTACCTGCAGAACAACCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGC AGGTCATCTACCTATACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAG CTGCACCTGCAGGACAACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGA GAAGCTGCACCTGGATGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCA AACAGCTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACG CTGGAGGAGCTGCGGCTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAA CAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCA GCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTG CCCAGCGCCCACCTGCAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCT GGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCC TGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAAC CTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCA GGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGA CGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACC ACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACAT TGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAG ACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTG GGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCT GACAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACG TAGCTGATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTC AACCAGGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGC TCTGGTCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGA CCCGGGAGAGGGCCTACAACCGGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAG GATAACTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAA AGAGGAGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCA TTGGCTATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATAG GTCGACGGC

NOVl 9k, CG54254-07 SEQ ID NO: 316 674 aa MW at 74086.5kD Protein Sequence

MWAHPTATATTTPTA VTATWMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN DRGLTSIPADIPDDATTLYLQ1JNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQD NVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADS QLKLLFLSRNHLSSIPSGLPHTLEELR LDDlv iSTIPLHAFKGI-NSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHL QKLYLQDNAI SHI YN IJAK ®ELE LDLSNNNLTT GLFDDLG1«-AQ L RMNP FCGCN M DIWKAP ^VVNVRGLMCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGS LFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRIT KATLPASSFRLS LRLGHSPA VGSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQN AGPMASLPLAGI IGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKKDDYMESGTKKDNS IL EIRGPGLQMLPINPYRA EEYWHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT

NOVl 91, 13375078 SNP for SEQ ID NO: J2040 bp SNP: 34 A G

CG54254-04 317

DNA Sequence ORF Start: ORF Stop: TGA at 2023 ATG at 1

ATGGTGGTGGCACACCCCACCGCCACTGCCACCGCCACGCCCACTGCCACTGTCACGGCCACCGTTGTGA TGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGA GGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGG GGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAACCAGATCA ACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGA CCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGC ACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGT CCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAA CCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATC TCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGC TGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCG CAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACTCTACCTGCAGGACAAT GCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACA ACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAA CAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTC AACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCG AGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAG CAACCACGCCTCTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGC CTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGA AGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAG TTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACA GAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCA ATGCCTACGTAGCTGATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCAC CACACTCAACCAGGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCA GTGGCTCTGGTCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGC TGACCCGGGAGAGGGCCTACAACCGGGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAA GGATAACTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAA GAGGAGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTG GCTATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCC GCCCACCCGG

NOV191, 13375078 SNP for SEQ ID NO: 674 aa ISNP: Thr to Ala at position 12

CG54254-04 318

Protein Sequence r VAHP ATAT P A V TVVMTTA MD D F C G IAFL EVIDS TCPS CRCDNGFI C D GLTSIPADIPDDATTLYLQlJ QI NAGIPQDLKTKVlWQVIYLYElsroLDEFPIl^PRSLRELHLQDNNVR TIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRI

STIPLHAFKGLNSLRRLVLDGNLLA QRIADDTFSRLQNLTΞLSLVRNSLAAPPLNLPSAHLQKLYLQDN

AISHIPYNTl-AKMRELERLDLSNNlsrLTTLPRGLFDDLGNJ^QLLL^

NVRGLMCQGPEKVRGMAIKDITSEMDECFETGPQGGVA AAAKTTAS HASATTPQGSLFTLKAKRPGLR

LPDSNIDYPMATGDGAKTLAIHVKALTADSIRIT KATLPASSFRLS LRLGHSPAVGSITETLVQGDKT

EYLLTALEPKSTYIIC VTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMASLPLAGIIGGA

VALVFLFLVLGAIC YVHQAGELLTRERAYNRGSREKDDY ESGTKKDNSILEIRGPGLQMLPINPYRA

EEYWHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT

|NOV19m, 13376406 SNP for SEQ ID NO: 319 2040 bp SNP: 47 C/T

CG54254-04 ORF Start: ATG at 1 ORF Stop: TGA at 2023 DNA Sequence

ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGTCACTGTCACGGCCACCGTTGTGAT

GACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGAGG

TCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGA

CTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAACCAGATCAACAA

CGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGACCTGG

ATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATT

GCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCACCGT

CAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAA

CCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATCT

CCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTG

GCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAA

TTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACTCTACCTGCAGGACAATGCCA

TCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAAC

CTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCC

TTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGC

GGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGAC

GAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGC

CTCTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACT

CCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACG

GCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCT

GGGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGA

CAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCT

GATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGA

GCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCC

TCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCC

TACAACCGGGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGA

AATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACA

CTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCACGCGGGGC

TACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCCGCCCACCCGG

NOV19m, 13376406 SNP for SEQ ID NO: J674 aa jSNP: Ala to Val at position 16 CG54254-04 1320

Protein Sequence

MVVAHPTATATTTPTVTVTATVVMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCNDRG

LTSIPADIPDDATTLYLQNNQINNAGIPQDLKTK^VQVIYLYENDLDEFPINLPRSLRE]^LQDlsπsTVRTI

ARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSR HLSSIPSGLPHTLEELRLDDNRISTI

PLHAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSIAAPPliαsTLPSAHLQKLYLQDNAISH

IPYNTLA MRELER DLSNNNL PRGLFDDLGNrAQ R NPWFCGCN rø DWVKARAA VNVRG

MCQGPEKVRGMAIKDITSE DECFETGPQGGVANAAAKTTAS HASATTPQGSLFTLKAKRPGLRLPDSNI

DYP ATGDGA TLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAVGSITETLVQGDKTEYLLTAL

EPKSTYIICiWTMETSNAYVADETPVCAKAETADSYGPTTTIiNQEQNAGPMASLPLAGIIGGAVALVFLFL

VLGAICWYVHQAGELLTRERAY RGSREDDYMESGTKECDNSILEIRGPGLQMLPINPYRAKEEYVVHTIF

PSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT

NOV19n, 13375079 SNP for SEQ ID NO: 321 2040 bp SNP: 106 T/C

CG54254-04 ORF Start: ATG at 1 ORF Stop: TGA at 2023

DNA Sequence ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGTGAT GACCACGGCCACCATGGACCTGCGGGACTGGCTGCTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGAGG TCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGA CTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAACCAGATCAACAA CGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGACCTGG ATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATT GCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCACCGT CAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGA GCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATCTCCACCATC CCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCA GCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGG CCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACTCTACCTGCAGGACAATGCCATCAGCCAC ATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCAC GCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTT GTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTC ATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTT TGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCA CCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATT GACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTC CATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACA GCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTG GAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGAC ACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACG CTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTTCCTG GTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCTACAACCG GGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGAAATCCGCG GCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACACTATCTTC CCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCACGCGGGGCTACCGGGA CGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCCGCCCACCCGG

NOV19n, 13375079 SNP for SEQ ID NO: 674 aa I SNP: Phe to Leu at position 36

CG54254-04 322

Protein Sequence

MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLLLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCNDRG

LTSIPADIPDDATTLYLQNNQIlrøAGIPQDLKTKVNVQVIYLYEra3LDEFPINLPRSLRELHLQDNNVRTI

ARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSR HLSSIPSGLPHTLEELRLDDNRISTI

PLHAFKGLNSLRRLVLDG LLANQRIADDTFSRLQNLTELSLVRNSIiAAPPLIJLPSAHLQKLYLQDNAISH

IPY TLA MRELERLDLSNNI^TTLPRGLFDDLGNLAQLLLRlsmPWFCGC IiM LRDWVKARAAVVN^

MCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTAS HASATTPQGSLFTL AKRPGLRLPDSNI

DYPMATGDGAKTLAIHV ALTADSIRITWKATLPASSFRLS LRLGHSPAVGSITETLVQGD TEYLLTAL

EPKSTYIICMVT ETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMASLPLAGIIGGAVALVFLFL

VLGAICWYVHQAGELLTRERAYITOGSREKDDYMESGTKKDNSILEIRGPGLQMLPINPYRA EEYVVHTIF

PSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT

NOV19o, 13376405 SNP for SEQ ID NO: 323 2040 bp SNP: 344 A/T

CG54254-04 ORF Start: ATG at 1 ORF Stop: TGA at 2023

DNA Sequence

ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGTGAT GACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGAGG TCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGA CTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAACCAGATCAACAA CGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGTGAATGACCTGG ATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATT GCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCACCGT CAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGA GCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATCTCCACCATC CCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCA GCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGG CCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACTCTACCTGCAGGACAATGCCATCAGCCAC ATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCAC GCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTT GTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTC ATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTT TGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCA CCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATT GACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTC CATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACA GCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTG GAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGAC ACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACG CTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTTCCTG GTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCTACAACCG GGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGAAATCCGCG GCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACACTATCTTC CCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCACGCGGGGCTACCGGGA CGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCCGCCCACCCGG

NOV19o, 13376405 SNP for SEQ ID NO: 674 aa SNP: Glu to Val at position 115

CG54254-04 324

Protein Sequence

MVVAHPTATATTTPTATVTATVVMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCNDRG

LTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKV^

ARDSILARIPLLEi LHLDDNSVSτVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTI

PLECAFKGLNSLRRLVLDGjrLIANQRIADDTFSRLQNLTELSLVRNSIiAAPPIj LPSAHLQ LYLQDNAISH

IPYimJ O^RELERLDLSNMrøiTTLPRGLFDDLGNIAQLLLRrøPWFOT

MCQGPE VRG AIKDITSEMDECFETGPQGGVANAAAKTTAS HASATTPQGSLFTLKAKRPGLRLPDSNI

DYP ATGDGAKTIαAIHVKALTADSIRIT ATLPASSFRLSWLRLGHSPAVGSITETLVQGDKTΞYLLTAL

EPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMASLPLAGIIGGAVALVFLFL

VLGAIC YVHQAGELLTRERAYNRGSREKDDYMESGTKIODNSILEIRGPGLQMLPINPYRA EEYVVHTIF

PSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 19B.

Table 19B. Comparison of the NOV19 protein sequences.

NOV19a MVVAHPTATATTTPTATVTATW TTATMDLRDLFLCYGLIAFLTEVIDSTTCPSV

NOV19b GSAAAPFTGSIDSTTCPSV

NOV19c

NOV19d

NOV19e TGSMWAHPTATATTTPTATVTATWMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSV

NOV19f MWAHPTATATTTPTATVTATVV TTATMDLRD LFLCYGLIAFLTEVIDSTTCPSV

NOV19g MWAHPTATATTTPTATVTATVVMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSV

NOV19h TTCPSV

NOV19i MWAHPTATATTTPTATVTATWMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSV

N0V19J TATATTTPTATVTATVVMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSV

NOVl9k MWAHPTATATTTPTATVTATWMTTATMDLRD LFLCYGLIAFLTEVIDSTTCPSV

NOV19a CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND

NOV19b CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND

NOV19C GSAAAPFTGSDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND

NOV19d GSAAAPFTGSDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND

NOV19e CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND

NOV19f CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND NOVl9g CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND

NOV19h CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND

NOV19i CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND

NOV19J CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKT VNVQVIYLYEND

NOV19k CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND

NOV19a LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19b LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19c LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19d LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19e LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19f LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19g LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19h LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19i LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19J LDEFPINLPRPLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19k LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK

NOV19a QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ

NOV19b QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ

NOV19C QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAF GLNSLRRLVLDGNLLANQ

NOV19d QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ

NOV19e QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ

NOV19f QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ

NOV19g QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ

NOV19h QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ

NOV19i QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ

NOV19J QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ

NOV19k QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLRAFKGLNSLRRLVLDGNLLANQ

NOV19a RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE

NOV19b RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE

NOV19c RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE

NOV19d RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE

NOV19e RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE

NOV19f RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAΪMRELE

NOV19g RIADDTFSRLQNLTELSLVRNSLAAPPL YLQDNAISH PYNTLAKMRELE

NOV19h RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAEMRELE

NOV19i RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE

NOVl9j RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQ LYLQDNAISHIPYNTLAKMRELE

NOV19k RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHL KLYLQDNAISHIPYNTLAKMRELE

NOV19a RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLM LRD V ARAAVVNVRGLMC

NOV19b RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLM LRD VKARAAVVNVRGLMC

NOV19c RLDLSNNNLTTLPRGLFDDLG-LEGKGGRADPAFLY

NOV19d RLDLSNNNLTTLPRGLFDDLG-NLAQLLLRNNP FCGCNLM LRD VKARAAVVNVRGLM

NOVl9e RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLM LRDWVKARAAWNVRGLMC

NOV19f RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNP FCGCNLM LRD VKARAAVVNVRGLMC

NOV19g RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNP FCGCNLMWLRD VKARAAVVNVRGL C

NOVl9h RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNP FCGCNLM LRD VKARAAWNVRGLMC

NOV19i RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNP FCGCNLMWLRDWVKARAAVVNVRGLMC

NOVl9j RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNP FCGCNLM LRD VKARAAWNVRGLMC

NOV19k RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNP FCGCNLM LRDWVKARAAVVNVRGLMC

NOVl9a QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP

NOVl9b QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP

NOVl9c N0V19d CQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKR

N0V19e QGPEKVRG AIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP

N0V19f QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP

N0V19g QGPEKVRGMAIKDITSEVESVLRRAPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP

NOV19h QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP

NOV19i QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP

NOV19J QGPEKVRG AIKDITSEMDECFETGPQGGVANAAAKTTASNHATATTPQGSLFTLKAKRP

NOVl9k QGPEKVRG AIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP

NOV19a GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRIT KATLPASSFRLS LRLGHSPAV

NOV19b GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV

N0V19c

NOV19d PGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPA

N0V19e GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV

N0V19f GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRIT KATLPASSFRLS LRLGHSPAV

N0V19g GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRIT KATLPASSFRLS LRLGHSPAV

N0V19 GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLS LRLGHSPAV

N0V19i GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRIT KATLPASSFRLS LRLGHSPAV

N0V19J GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV

N0V19k GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV

NOV19a GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT

N0V19b GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT

NOVl9c

NOV19d VGSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPT

NOV19e GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT

NOV19f GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT

NOV19g GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT

NOV19h GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT

NOV19i GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT

NOVl9j GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT

NOV19k GSITETLVQGDKTEYLLTALEPKSTYIIC VTMETSNAYVADETPVCAKAETADSYGPTT

NOVl9a TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSREK

NOVl9b TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSRKK

NOVl9c

NOV19d TTLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSRK

NOVl9e TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSRKK

NOV19f TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSRKK

NOV19g TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKK

NOV19h TLNQEQNAG

NOV19i TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSRKK

NOVl9j TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSRKK

NOV19k TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAIC YVHQAGELLTRERAYNRGSRKK

NOV19a DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGT

NOV19b DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGT

NOVl9c

NOV19d KDDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYG

NOV19e DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGT

NOV19f DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGT

NOV19g DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGT

NOV19h

NOV19i DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGT

NOVl9j DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGT

NOV19k DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYWHTIFPSNGSSLCKATHTIGYGT NOV19a TRGYRD-GGIPDIDYSYT

NOVl 9b TRGYRD-GGIPDIDYSYTLEGKGGRA

NOV19c

NOV19d TTRGYRDGGIPDIDYSYTLEGKGGRPDPAFLYTAGIIRSHC

NOV19e TRGYRD-GGIPDIDYSYTLEG

NOV19f TRGYRD-GGIPDIDYSYT

NOV19g TRGYRD-GGIPDIDYSYT

NOV19h

NOV19i TRGYRD-GGIPDIDYSYT

NOVl9j TRGYRHCHHLPDIDYSYTRSPT

NOV19k TRGYRD-GGIPDIDYSYT

NOVl9a (SEQ ID NO 296)

NOVl9b (SEQ ID NO 298)

NOVl9c (SEQ ID NO 300)

NOV19d (SEQ ID NO 302)

NOV19e (SEQ ID NO 304)

NOVl9f (SEQ ID NO 306)

NOV19g (SEQ ID NO 308)

NOV19h (SEQ ID NO 310)

NOV19i (SEQ ID NO 312)

NOVl9j (SEQ ID NO 314)

NOVl9k (SEQ ID NO 316)

Further analysis of the NOVl 9a protein yielded the following properties shown in Table 19C.

Table 19C. Protein Sequence Properties NOV19a

SignalP analysis: Cleavage site between residues 52 and 53

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 0; pos.chg 0; neg.chg 0 H-region: length 29; peak value 8.99 PSG score: 4.59

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.42 possible cleavage site: between 53 and 54

>» Seems to have no N-terminal signal peptide

ALOM: Klein et al ' s method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0. Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood =-10.46 Transmembrane 553 569 PERIPHERAL Likelihood = 4.93 (at 493) ALOM score: -10.46 (number of TMSs: 1)

MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 560 Charge difference: 4.5 C( 1.5) - N(-3.0) C > N: C-terminal side will be inside

>» membrane topology: type Nt (cytoplasmic tail 1 to 552)

MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment (75) : 3.83 Hyd Moment (95): 1.63 G content: 0 D/E content: 1 S/T content: 12 Score: -2.21

NUCDISC: discrimination of nuclear localization signals pa 4: none pat7: none bipartite: none content of basic residues: 9.2% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals : none

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2: none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: too long tail

Dileucine motif in the tail: found LL at 152 LL at 181 LL at 233 LL at 323 LL at 324 checking 63 PROSITE DNA binding motifs:

Leucine zipper pattern (PS00029) : *** found *** LFLSRNHLSSIPSGLPHTLEEL at 182 LDLSNNNLTTLPRGLFDDLGNL at 299 none checking 71 PROSITE ribosomal protein motifs : none checking 33 PROSITE prokaryotic DNA binding motifs : none

NNCN : Reinhardt ' s method for Cytoplasmic/Nuclear discrimination Prediction : nuclear Reliability : 55 . 5

COIL : Lupas ' s algorithm to detect coiled-coil regions total : 0 residues

Final Results ( k = 9/23 )

30.4 9- • nuclear

26.1 cytoplasmic

13.0 Golgi

13.0 mitochondrial

8.7 9o- -_* endoplasmic reticulum

4.3 9o, ■• vesicles of secretory system

4.3 Ό • peroxisomal

» prediction for CG54254-04 is nuc (k=23 )

A search of the NOVl 9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 19D.

In a BLAST search of public sequence databases, the NOVl 9a protein was found to have homology to the proteins shown in the BLASTP data in Table 19E.

PFam analysis predicts that the NOVl 9a protein contains the domains shown in the Table 19F.

Example 20.

The NOV20 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 20A.

Table 20A. NOV20 Sequence Analysis

NOV20a, CG96778-02 SEQ ID NO: 325 ^'fl365 b T DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 1363

ATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGATCACA GCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAGCAGA AAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATATGAT AAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACACAT TCCAGAGAACTGTGACTACAGTGTTTGCCCACTTTTGGAAGCTTGCACTCTATACCTAGATGCGTTTT TCCTTCTTCTAACTGGTTCCAACCTTAACTTGCACCTAAACCTTGGAGGTCTTGGACTTGGAACTTTT GATGCTTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAA TTCTTTGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAA TGACTGAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGT ATAAAGACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAA CGGAGGAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGCTAATA AAGCCTTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAGAAAGGAATTAAAC ATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATGT TTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAG CTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAA ACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGT TGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATT ATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATA CTTGGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAACTAATGAGGGATGCCAAAATCTATCA GATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAAAA ATTAA

NOV20a, CG96778-02 SEQ ID NO: 326 1454 aa MW at 50270.1kD Protein Sequence

MAAGFGRCCRVLRSISRFH RSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEYD KTGEYPVPLIRRA ELGLMNTHIPENCDYSVCPLLEACTLYLDAFFLLLTGSNLNLHLNLGGLGLGTF DACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQQ KKYLGRMTEEPLMCAYCVTEPGAGSDVAG IKTKAEKKGDEYIINGQKM ITNGGKANWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKΞLN MGQRCSDTRGIVFEDVKVPKElsrv/LIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERK TFGKLLVEHQAISFMIiAEMAMKVEIiARMSYQRAA EVDSGRRNTYYASIAKAFAGDIANQLATDAVQI LGGNGFNTEYPVE LMRDAKIYQIYEGTSQIQRLIVAREHIDKYKN

NOV20b, CG96778-01 SEQ ID NO: 327 13387 bp DNA Sequence ORF Start: ATG at 1387 jORF Stop: TAA at 2650

CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACAT GTTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAG GCATATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGG AACAAAGGAGACATGAATAGACAATTCCTAATCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACA

CCACCACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTT

CCTGGTACTTTCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTA

TAAATTCCCAGAAGACAAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGAT iGAATTTATGGGTGACCTTTATTGGGCAAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTAC

CACTCAAAACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCA

CTTCCATCATTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCA

CATCAGCGGACAAGTCATAAACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAA

TTCTCTTTTAAATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATG

TACTAATACTTTGAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAA

GGCTGACCACGGGGCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCAC

CGCGCCGCAAGTCCCCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCG

CCCTGGCTCTCTTTCCGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAG

IAAAACCAAACCAGGACTATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGAC

GGCGCACGCAAGGGTCACGGAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAG

CGCAGCGCCCCGTCCTTCCGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTC

CAGTGGGCGGGACCAGAGGAGTCCCGCGTTCGGGGAGTATGTCAAGGCCGTGACCCGTGTATTATTGT

CCGAGTGGCCGGAACGGAGAGCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGT

ATTTCTCGTTTTCATTGGAGATCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATT TAGTTTTGAGTTCACCGAACAGCAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAA TCATCCCAGTGGCTGCAGAATATGATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGG GAACTTGGTTTAATGAACACACACATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGC TTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTT TGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACT GAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAA GACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAG GAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCC TTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGG CCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAA TTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCT GGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTT CGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGTTGAAC TAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATGCT TCTATTGCAAAGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATACTTGG AGGCAATGGATTTAATACAGAATATCCTGTAGAAAAACTAATGAGGGATGCCAAAATCTATCAGATTT ATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAAAAATTAA AAAAATTACTGTAGAAATATTGAATAACTAGAACACAAGCCACTGTTTCAGCTCCAGAAAAAAGAAAG

GGCTTTAACGTTTTTTCCAGTGAAAACAAATCCTCTTATATTAAATCTAAGCAACTGCTTATTATAGT

AGTTTATACTTTTGCTTAACTCTGTTATGTCTCTTAAGCAGGTTTGGTTTTTATTAAAATGATGTGTT

TTCTTTAGTACCACTTTACTTGAATTACATTAACCTAGAAAACTACATAGGTTATTTTGATCTCTTAA

GATTAATGTAGCAGAAATTTCTTGGAATTTTATTTTTGTAATGACAGAAAAGTGGGCTTAGAAAGTAT

TCAAGATGTTACAAAATTTACATTTAGAAAATATTGTAGTATTTGAATACTGTCAACTTGACAGTAAC

TTTGTAGACTTAATGGTATTATTAAAGTTCTTTTTATTGCAGTTTGGAAAGCATTTGTGAAΑCTTTCT

GTTTGGCACAGAAACAGTCAAAATTTTGACATTCATATTCTCCTATTTTACAGCTACAAGAACTTTCT

TGAAAATCTTATTTAATTCTGAGCCCATATTTCACTTACCTTATTTAAAATAAATCAATAAAGCTTGC

CTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCTATTGTACACAATCTCATTTC jATATGTTTGCATTTTGGCAAAGAACTTAATAAAATTGTTCAGTGCTTATTATCAT

NOV20b, CG96778-01 SEQ ID NO: 328 421 aa MW at 46587.9kD Protein Sequence

MAAGFGRCCRVLRSISRFH RSQHT ANRQREPGLGFSFΞFTEQQKEFQATARKFAREEIIPVAAEYD KTGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIA GOT QQKKKYLGR TEEPL CAYCVTEPGAGSDVAGIKTKAEK3 GDEYIINGQKMWITNGGKAN YFLL ARSDPDPIS^PAN AFTGFIVEADTPGIQIGRK^IJMGQRCSDTRGIVFEDVICVPKENVLIGDGAGFKV AMGAFDKTRPWAAGAVGLAQRALDE ATKYALERKTFGKLLVEHQAI S FMLAEMAMKVELARMS YQRA A FΛΠSSGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQR LIVAREHIDKYKN

SEQ ID NO: 329 1288 bp TRSPTMAAGFGRCCRVLRSISRFH RSQHTKANRQRΞPGLGFSFEFTEQQKEFQATARKFAREEIIPV AAEYDKTGEYPVPLIRRA ELGLMNTHIPENCDYSVCPLLEACTLYLDAFFLLLTGSNLNLHLNLGGL GLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAG SDVAGIKTKAEKKGDEYIINGQKM ITNGGKANWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIG RELIMGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKY ALERKTFGKLLVEHQAISFMI_AEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLAT DAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKNVDG

NOV20e, 276657538 SEQ ID NO: 333 1300 bp DNA Sequence

ORF Start: at 2 ORF Stop: end ofsequence

CACCAGATCTCCCACCATGGCAGCGGGGTTCGGGCGATGCTGCAGGTGTTCTTTACAGGTCCTGAGAA GTATTTCTCGTTTTCATTGGAGATCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGA TTTAGTTTTGAGTTCACCGAACAGCAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGA AATCATCCCAGTGGCTGCAGAATATGATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCT GGGAACTTGGTTTAATGAACACACACATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGAT GCTTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTC TTTGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGA CTGAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATA AAGACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAACGG AGGAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAΆAGCTCCTGCTAATAAAG CCTTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAAAAAGGAATTAAACATG GGCCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTT AATTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAGCTG CTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAACT TTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGTTGA ACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATG CTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATACTT GGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAACTAATGAGGGATGCCAAAATCTATCAGAT TTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAAAAATG TCGACGGC

NOV20e, 276657538 SEQ ID NO: 334 433 aa MWat47805.2kD Protein Sequence RSPTMAAGFGRCCRCSLQVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREE

IIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNS GQMPIiIAGNDQQKKKYLGRMTEEPLMCAYCVTΞPGAGSDVAGIKTKAEKKGDEYIINGQKM ITNG

GKANVTCFLI_JARSDPDPKAPALΩVA.FTGFIVEADTPGIQIGK3Α3LN^

IGDGAGFKVAMGAFDKTRPVVAAGAVGIAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVE

LARMSYQRAA EVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQI

YEGTSQIQRLIVAREHIDKYKNVDG

NOV20f, 276657616 SEQ ID NO: 335 1147bp DNA Sequence ORF Start: at 2 ORF Stop: end ofsequence

CACC6AGATCTTTCACCGAACAGCAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAA CATCCCAGTGGCTGCAGAATATGATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGG

GAACTTGGTTTAATGAACACACACATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGC TGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTT

TGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACT

GAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAA

GACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAG

GAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCC

TTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGG

CCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAA

TTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCT

GGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTT

CGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGTTGAAC CCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGACAAGTCATAA

ACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAATTCTCTTTTAAATTTTAAGGAA

ACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTAATACTTTGAATCCGCCAAG

CAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAAGGCTGACCACGGGGCCGCTCTCCCTC

CAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCAAGTCCCCCCACCGTTCAGC

GCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTCCGCGCTGCGTCAGCC CGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGACTATCAGAGATTGCCCG

IGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCACGGAGCATGCGTTGGCT

ATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTCCGCAGCCCAACCGCCTCT

TCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGGAGTCCCGCGTTCGGGGAGT

ATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGAGCCAACATGGCAGCGGGGTT

CGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGATCACAGCATACAAAAGCCAAT CGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAGCAGAAAGAATTTCAAGCTACTG CTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATATGATAAAACTGGTGAATATCCAGT CCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACACATTCCAGAGAACTGTGTAGGTCTT GGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTG CTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTA TTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGA GTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGA TAACCAACGGAGGAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGC TAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAGAAAGGAATTA AACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATG TTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAGC TGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAACT TTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGTTGAAC TAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATGCTTC ATTGCAAAGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGC AATGGATTTAATACAGAATATCCTGTAGAAAAACTAATGAGGGATGCCAAAATCTATCAGATTTATGAAG GTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAAAAATTAAAAAAATTA

CTGTAGAAATATTGAATAACTAGAACACAAGCCACTGTTTCAGCTCCAGAAAAAAGAAAGGGCTTTAACG

TTTTTTCCAGTGAAAACAAATCCTCTTATATTAAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTT

TGCTTAACTCTGTTATGTCTCTTAAGCAGGTTTGGTTTTTATTAAAATGATGTGTTTTCTTTAGTACCAC TTACTTGAATTACATTAACCTAGAAAACTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAA

IATTTCTTGGAATTTTATTTTTGTAATGACAGAAAAGTGGGCTTAGAAAGTATTCAAGATGTTACAAAATT

TACATTTAGAAAATATTGTAGTATTTGAATACTGTCAACTTGACAGTAACTTTGTAGACTTAATGGTATT

ATTAAAGTTCTTTTTATTGCAGTTTGGAAAGCATTTGTGAAACTTTCTGTTTGGCACAGAAACAGTCAAA

ATTTTGACATTCATATTCTCCTATTTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGC

CCATATTTCACTTACCTTATTTAAAATAAATCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTG

GTCTCTAGGTAGCCTTTGGTCTATTGTACACAATCTCATTTCATATGTTTGCATTTTGGCAAAGAACTTA

IATAAAATTGTTCAGTGCTTATTATCAT

NOV20h, 13382351 SNP for SEQ ID NO: 421 aa SNP: Gly to Val at position 96 CG96778-01 ]340

Protein Sequence

MAAGFGRCCRVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEYDKT GEYPVPLIRRAWELGLMNTHIPENCVGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQ QKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKM ITNGGKANWYFLLARSDPD PKAPANKAFTGFIVEADTPGIQIGRKELI^GQRCSDTRGIVFEDVKVPKEISTVLIGDGAGFKVAMGAFDKT

RPWAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAI S FMLAEMAMKVELARMS YQRAA EVDSGRRlsT

TYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYK

N

NOV20i, 13382352 SNP for SEQ ID NO: 341 3387 bp SNP: 1717

CG96778-01 G/C

DNA Sequence ORF Start: ATG at ORF Stop: TAA at 11387 2650

CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACATG TTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAGGC IATATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGGAAC

AAAGGAGACATGAATAGACAATTCCTAATCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACACCAC

CACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTTCCTGG

TACTTTCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTATAAATT

CCCAGAAGACAAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGATGAATTTA

TGGGTGACCTTTATTGGGCAAAAGAAAΆTGTTAAGTTAGTATAAGATTTAGTATAAGCTACCACTCAAA

ACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCACTTCCATCA

TTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGA

CAAGTCATAAACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAATTCTCTTTTAA

ATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTAATACTTT

GAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAAGGCTGACCACGGG

GCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCAAGTCC

CCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTC

CGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGAC ATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCA

CGGAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTC

CGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGG

AGTCCCGCGTTCGGGGAGTATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGA

GCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGA

TCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAG CAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATAT GATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACAC ATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAACAATTGGCT TATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCT GGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGT GTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAG TATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAAAAGCTAATTGGTATTTTTTATTGGCA CGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACC CCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTC TTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATG GGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGAT GAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCA TTTATGCTGGCTGAAATGGCAATGAAAGTTGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAG GTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAAT CAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAA CTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCC CGTGAACACATTGACAAGTACAAAAATTAAAAAAATTACTGTAGAAATATTGAATAACTAGAACACAAG CCACTGTTTCAGCTCCAGAAAAAAGAAAGGGCTTTAACGTTTTTTCCAGTGAAAACAAATCCTCTTATA

TTAAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTTTGCTTAACTCTGTTATGTCTCTTAAGCAG

GTTTGGTTTTTATTAAAATGATGTGTTTTCTTTAGTACCACTTTACTTGAATTACATTAACCTAGAAAA

CTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAAATTTCTTGGAATTTTATTTTTGTAATG jACAGAAAAGTGGGCTTAGAAAGTATTCAAGATGTTACAAAATTTACATTTAGAAAATATTGTAGTATTT

GAATACTGTCAACTTGACAGTAACTTTGTAGACTTAATGGTATTATTAAAGTTCTTTTTATTGCAGTTT

GGAAAGCATTTGTGAAACTTTCTGTTTGGCACAGAAACAGTCAAAATTTTGACATTCATATTCTCCTAT

TTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGCCCATATTTCACTTACCTTATTTA

AAATAAATCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCT

ATTGTACACAATCTCATTTCATATGTTTGCATTTTGGCAAAGAACTTAATAAAATTGTTCAGTGCTTAT

TATCAT

NOV20i, 13382352 SNP for SEQ ID NO: 421 aa SNP: Glu to Gin at position

CG96778-01 342 111

Protein Sequence

MAAGFGRCCRVLRS SRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREE I IPVAAEYDK TGEYPVPLIRRA ELGLMNTHIPENCGGLGLGTFDACLISEQLAYGCTGVQTAIEGNSLGQMPIIIAGN DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYI INGQKM ITNGGKANWYFLLARS DPDPIv PANKAFTGFIVEADTPGIQIGRKELM lGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGA FDKTRP WAAGAVGLAQRALDE ATKYALERKTFGKLLVEHQAI S FMLAEMAMKVELARMS YQRAA EVD SGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVARE HIDKYKN

NOV20J, 13382353 SNP for SEQ ID NO: 343 J3387 bp SNP: 2204 C/T

CG96778-01 iORF Start: ATG at 1387 |ORF Stop: TAA at 2650

DNA Sequence j j

CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACATG

TTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAGGC

ATATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGGAAC

AAAGGAGACATGAATAGACAATTCCTAATCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACACCAC

CACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTTCCTGG

TACTTTCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTATAAATT

CCCAGAAGACAAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGATGAATTTA

TGGGTGACCTTTATTGGGCAAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTACCACTCAAA

ACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCACTTCCATCA

TTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGA

CAAGTCATAAACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAATTCTCTTTTAA

ATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTAATACTTT

GAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAAGGCTGACCACGGG

GCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCAAGTCC

CCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTC

CGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGAC

TATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCA

CGGAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTC

CGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGG

AGTCCCGCGTTCGGGGAGTATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGA

GCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGA

TCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAG CAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATAT GATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACAC ATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCT TATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCT GGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGT GTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAG TATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAAAAGCTAATTGGTATTTTTTATTGGCA CGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACC CCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTC TTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGTAATG GGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGAT GAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCA TTTATGCTGGCTGAAATGGCAATGAAAGTTGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAG GTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAAT CAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAA CTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCC CGTGAACACATTGACAAGTACAAAAATTAAAAAAATTACTGTAGAAATATTGAATAACTAGAACACAAG CCACTGTTTCAGCTCCAGAAAAAAGAAAGGGCTTTAACGTTTTTTCCAGTGAAAACAAATCCTCTTATA

TTAAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTTTGCTTAACTCTGTTATGTCTCTTAAGCAG

GTTTGGTTTTTATTAAAATGATGTGTTTTCTTTAGTACCACTTTACTTGAATTACATTAACCTAGAAAA

CTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAAATTTCTTGGAATTTTATTTTTGTAATG

ACAGAAAAGTGGGCTTAGAAAGTATTCAAGATGTTACAAAATTTACATTTAGAAAATATTGTAGTATTT

GAATACTGTCAACTTGACAGTAACTTTGTAGACTTAATGGTATTATTAAAGTTCTTTTTATTGCAGTTT

GGAAAGCATTTGTGAAACTTTCTGTTTGGCACAGAAACAGTCAAAATTTTGACATTCATATTCTCCTAT

TTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGCCCATATTTCACTTACCTTATTTA

AAATAAATCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCT

ATTGTACACAATCTCATTTCATATGTTTGCATTTTGGCAAAGAACTTAATAAAATTGTTCAGTGCTTAT

TATCAT

NOV20J, 13382353 SNP for SEQ ID NO: 344 421 aa SNP: Ala to Val at 273

CG96778-01

Protein Sequence MAAGFGRCCRVLRSISRFH RSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEYDK TGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDΞYIINGQKM ITNGGKAN YFLLARS DPDPKAPANKAFTGFIVEADTPGIQIGRKELlSMGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVyMGA FDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVD SGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVARE HIDKYKN

NOV20k, 13382354 SNP for SEQ ID NO: 345 3387 bp SNP: 2547 A/G

CG96778-01 ORF Start: ATG at 1387 ORF Stop: TAA at 2650

DNA Sequence

CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACATG

TTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAGGC

ATATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGGAAC

AAAGGAGACATGAATAGACAATTCCTAATCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACACCAC

CACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTTCCTGG

TACTTTCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTATAAATT

CCCAGAAGACAAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGATGAATTTA

TGGGTGACCTTTATTGGGCAAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTACCACTCAAA

ACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCACTTCCATCA

TTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGA

CAAGTCATAAACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAATTCTCTTTTAA

ATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTAATACTTT

GAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAAGGCTGACCACGGG

GCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCAAGTCC

CCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTC

CGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGAC iTATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCA

CGGAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTC

CGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGG

AGTCCCGCGTTCGGGGAGTATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGA

GCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGA

TCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAG CAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATAT GATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACAC ATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCT TATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCT GGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGT GTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAG TATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAAAAGCTAATTGGTATTTTTTATTGGCA CGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACC CCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTC TTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATG GGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGAT GAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCA TTTATGCTGGCTGAAATGGCAATGAAAGTTGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAG GTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAAT CAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGATTTAATACAGAATATCCTGTGGAAAAA CTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCC CGTGAACACATTGACAAGTACAAAAATTAAAAAAATTACTGTAGAAATATTGAATAACTAGAACACAAG CCACTGTTTCAGCTCCAGAAAAAAGAAAGGGCTTTAACGTTTTTTCCAGTGAAAACAAATCCTCTTATA

TTAAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTTTGCTTAACTCTGTTATGTCTCTTAAGCAG

GTTTGGTTTTTATTAAAATGATGTGTTTTCTTTAGTACCACTTTACTTGAATTACATTAACCTAGAAAA

CTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAAATTTCTTGGAATTTTATTTTTGTAATG

ACAGAAAAGTGGGCTTAGAAAGTATTCAAGATGTTACAAAATTTACATTTAGAAAATATTGTAGTATTT

IGAATACTGTCAACTTGACAGTAACTTTGTAGACTTAATGGTATTATTAAAGTTCTTTTTATTGCAGTTT

GGAAΆGCATTTGTGAAACTTTCTGTTTGGCACAGAAACΆGTCAAAATTTTGACATTCATATTCTCCTAT

TTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGCCCATATTTCACTTACCTTATTTA AAATAAΆTCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCT

ATTGTACACAATCTCATTTCATATGTTTGCATTTTGGCAAAGAACTTAATAAAATTGTTCAGTGCTTAT

TATCAT

NOV20k, 13382354 SNP SEQ ID NO: 421 aa SNP: no change in the protein for 346 sequence

CG96778-01

Protein Sequence

MAAGFGRCCRVLRSISRFH RSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREE11PVAAEYDK TGEYPVPLIRRA ELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKM ITNGGKANWYFLLARS DPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGA FDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVD SGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVARE HIDKYKN

NOV201, 12252113 SNP for SEQ ID NO: 347 3387 bp SNP: 3324

CG96778-01 T/C

DNA Sequence iORF Start: ATG at ORF Stop: TAA at 1387 2650

CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACATG

TTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAGGC

ATATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGGAAC

AAAGGAGACATGAATAGACAATTCCTAATCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACACCAC

CACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTTCCTGG

TACTTTCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTATAAATT

CCCAGAAGACAAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGATGAATTTA iTGGGTGACCTTTATTGGGCAAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTACCACTCAAA

ACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCACTTCCATCA

TTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGA

CAAGTCATAAACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAATTCTCTTTTAA

ATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTAATACTTT

GAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAAGGCTGACCACGGG

GCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCAAGTCC

CCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTC

CGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGAC

TATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCA

CGGAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTC

CGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGG lAGTCCCGCGTTCGGGGAGTATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGA

GCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGA

TCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAG CAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATAT GATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACAC ATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCT TATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCT GGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGT GTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAG TATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAAAAGCTAATTGGTATTTTTTATTGGCA CGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACC CCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTC TTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATG GGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGAT GAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCA TTTATGCTGGCTGAAATGGCAATGAAAGTTGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAG GTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAAT CAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAA CTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCC CGTGAACACATTGACAAGTACAAAAATTAAAAAAATTACTGTAGAAATATTGAATAACTAGAACACAAG CCACTGTTTCAGCTCCAGAAAAAAGAAAGGGCTTTAACGTTTTTTCCAGTGAAAACAAATCCTCTTATA TTAAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTTTGCTTAACTCTGTTATGTCTCTTAAGCAG

GTTTGGTTTTTATTAAAATGATGTGTTTTCTTTAGTACCACTTTACTTGAATTACATTAACCTAGAAAA

CTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAAATTTCTTGGAATTTTATTTTTGTAATG lACAGAAAAGTGGGCTTAGAAAGTATTCAAGATGTTACAAAATTTACATTTAGAAAATATTGTAGTATTT

GAATACTGTCAACTTGACAGTAACTTTGTAGACTTAATGGTATTATTAAAGTTCTTTTTATTGCAGTTT

GGAAAGCATTTGTGAAACTTTCTGTTTGGCACAGAAACAGTCAAAATTTTGACATTCATATTCTCCTAT

TTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGCCCATATTTCACTTACCTTATTTA jAAATAAATCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCT jATTGTACACAACCTCATTTCATATGTTTGCATTTTGGCAAAGAACTTAATAAAATTGTTCAGTGCTTAT

TATCAT

NOV201, 12252113 SNP for SEQ ID NO: 421 aa SNP is in the non coding

CG96778-01 348 region

Protein Sequence

MAAGFGRCCRVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEYDK TGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKANWYFLLARS DPDPKAPANKAFTGFIVEADTPGIQIGRKEIJvmGQRCSDTRGIVFEDVIWPKENVLIGDGAGFKVAMGA FDKTRPWAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVD SGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVARE HIDKYKN

A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 20B.

Table 20B. Comparison ofthe NOV20 protein sequences.

NOV20a MAAGFGRCCR VLRSISRFH RSQHTKANRQREPGLGFSFEFTEQQKEFQAT

NOV20b MAAGFGRCCR VLRSISRFH RSQHTKANRQREPGLGFSFEFTEQQKEFQAT

NOV20C TRSPTMAAGFGRCCR VLRSISRFH RSQHTKANRQREPGLGFSFEFTEQQKEFQAT

NOV20d TRSPTMAAGFGRCCR VLRSISRFH RSQHTKANRQREPGLGFSFEFTEQQKEFQAT

NOV20e TRSPTMAAGFGRCCRCSLQVLRSISRFH RSQHTKANRQREPGLGFSFEFTEQQKEFQAT

NOV20f TRSFTEQQKEFQAT

NOV20g MAAGFGRCCRCSLQVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQAT

NOV20a ARKFAREEIIPVAAEYDKTGEYPVPLIRRA ELGLMNTHIPENCDYSVCPLLEACTLYLD

NOV20b ARKFAREEIIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPEN C

NOV20c ARKFAREEIIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCG

NOV20d ARKFAREEIIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCDYSVCPLLEACTLYLD

NOV20e ARKFAREEIIPVAAEYDKTGEYPVPLIRRA ELGLMNTHIPENCG

NOV20f ARKFAREEIIPVAAEYDKTGEYPVPLIRRA ELGLMNTHIPENCG

NOV20g ARKFAREEIIPVAAEYDKTGEYPVPLIRRA ELGLMNTHIPENCG

NOV20a AFFLLLTGSNLNLHLNLGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN

NOV20b G GLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN

NOV20c G LGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN

NOV20d AFFLLLTGSNLNLHLNLGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN

NOV20e G LGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN

NOV20f GLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN

NOV20g G LGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN

NOV20a DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTΪCAEKKGDEYIINGQKM ITNGGKA

NOV20b DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKA

NOV20c DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKM ITNGGKA

NOV20d DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKM ITNGGKA

NOV20e DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKM ITNGGKA

NOV20f DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKA

NOV20g DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKM ITNGGKA

NOV20a N YFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP

NOV20b NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP

NOV20C N YFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP

NOV20d NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP

NOV20e NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGKKELNMGQRCSDTRGIVFEDVKVP

NOV20f N YFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP

NOV20g N YFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGKKELNMGQRCSDTRGIVFEDVKVP

NOV2Oa KENVLIGDGAGFKVAMGAFDKTRPWAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA

NOV2Ob KENVLIGDGAGFKVAMGAFDKTRPWAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA

NOV20C KENVLIGDGAGFKVAMGAFDKTRPWAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA

NOV20d KENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA

NOV20e KENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA

NOV20f KENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA

NOV2Og KENVLIGDGAGFKVAMGAFDKTRPWAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA

NOV20a ISFMLAEMAMKVELARSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG

NOV20b ISFMLAEMAMKVELARMSYQRAA EVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG

NOV20C ISFMLAEMAMKVELARMSYQRAA EVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG

N_OV20d ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG

N_OV20e ISFMLAEMAMKVELARMSYQRAA EVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG NOV20f ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG NOV20g ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG

NOV20a NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKN NOV20b NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKN NOV20c NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKNVDG NOV20d NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKNVDG NOV20e NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKNVDG NOV20f NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIVDG NOV20g NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKN

NOV20a (SEQ ID NO 326) NOV20b (SEQ ID NO 328) NOV20c (SEQ ID NO 330) NOV20d (SEQ ID NO 332) NOV20e (SEQ ID NO 334) NOV20f (SEQ ID NO 336) NOV20g (SEQ ID NO 338)

Further analysis ofthe NOV20a protein yielded the following properties shown in Table 20C.

Table 20C. Protein Sequence Properties NOV20a

SignalP analysis: INo Known Signal Sequence Predicted

PSORT II analysis:

PSG: a new signal peptide prediction method

N-region: length 10; pos . chg 2; neg.chg 0 H-region: length 2; peak value -5.86 PSG score: -10.26

GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -9.99 possible cleavage site: between 14 and 15

>» Seems to have no N-terminal signal peptide

Tentative number of TMS(s) for the threshold 0.5; 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 3.39 (at 126) ALOM score: -0.90 (number of TMSs : 0)

MITDISC: discrimination of mitochondrial targeting seq R content: 7 Hyd Moment(75): 6.98 Hyd Moment (95): 9.53 G content: 2 D/E content: 1 S/T content: 4 Score: 2.17

Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 39 NRQ|RE NUCDISC: discrimination of nuclear localization signals pat4: none pat7 : none bipartite: none content of basic residues: 12.1% NLS Score: -0.47

KDEL: ER retention motif in the C-terminus: none

ER Membrane Retention Signals:

KKXX-like motif in the C-terminus: DKYK

SKL: peroxisomal targeting signal in the C-terminus: none

PTS2: 2nd peroxisomal targeting signal: none

VAC: possible vacuolar targeting motif: none

RNA-binding motif: none

Actinin-type actin-binding motif: type 1 : none type 2 : none

NMYR: N-myristoylation pattern : none

Tyrosines in the tail: none

Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: Leucine zipper pattern (PS00029) : *** found *** LEACTLYLDAFFLLLTGSNLNL at 103 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none

COIL: Lupas ' s algorithm to detect coiled-coil regions total: 0 residues

Final Results (k = 9/23)

91.3 %: mitochondrial 4.3 % : nuclear 4.3 % : peroxisomal » prediction for CG96778-02 is mit ( k=23)

A search of the NOV20a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 20D.

In a BLAST search of public sequence databases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20E.

PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20F.

Example B: Sequencing Methodology and Identification of NOVX Clones

1. GeneCalling™ Technology: This is a proprietary method of performing differential gene expression profiling between two or more samples developed at CuraGen and described by Shimkets, et al., "Gene expression analysis by transcript profiling coupled to a gene database query" Nature Biotechnology 17:198-803 (1999). cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then digested with up to as many as 120 pairs of restriction enzymes and pairs of linker-adaptors specific for each pair of restriction enzymes were ligated to the appropriate end. The restriction digestion generates a mixture of unique cDNA gene fragments. Limited PCR amplification is performed with primers homologous to the linker adapter sequence where one primer is biotinylated and the other is fluorescently labeled. The doubly labeled material is isolated and the fluorescently labeled single strand is resolved by capillary gel electrophoresis. A computer algorithm compares the electropherograms from an experimental and control group for each of the restriction digestions. This and additional sequence-derived information is used to predict the identity of each differentially expressed gene fragment using a variety of genetic databases. The identity of the gene fragment is confirmed by additional, gene-specific competitive PCR or by isolation and sequencing of the gene fragment.

2. SeqCalling™ Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen's proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.

3. PathCalling™ Technology: The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.

The laboratory screening was performed using the methods summarized below: cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, CA) were then transferred from E.coli into a CuraGen Corporation proprietary yeast strain (disclosed in U. S. Patents 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).

Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Gal4-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95%) over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.

Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Corporation proprietary yeast strains N106' and YULH (U. S. Patents 6,057,101 and 6,083,693).

4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of cDNA ends (RACE), were used to isolate or complete the predicted sequence of the cDNA of the invention. Usually multiple clones were sequenced from one or more human samples to derive the sequences for fragments. Various human tissue samples from different donors were used for the RACE reaction. The sequences derived from these procedures were included in the SeqCalling Assembly process described in preceding paragraphs.

5. Exon Linking: The NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation's database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least 95% over 50 bp. In addition, sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.

6. Physical Clone: Exons were predicted by homology and the intron/exon boundaries were determined using standard genetic rules. Exons were further selected and refined by means of similarity determination using multiple BLAST (for example, tBlastN, BlastX, and BlastN) searches, and, in some instances, GeneScan and Grail. Expressed sequences from both public and proprietary databases were also added when available to further define and complete the gene sequence. The DNA sequence was then manually corrected for apparent inconsistencies thereby obtaining the sequences encoding the full-length protein.

The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.

Example C: Quantitative expression analysis of clones in various cells and tissues

The quantitative expression of various NOV genes was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ-PCR) performed on an Applied Biosystems (Foster City, CA) ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System.

RNA integrity of all samples was determined by visual assessment of agarose gel electropherograms using 28S and 18S ribosomal RNA staining intensity ratio as a guide (2:1 to 2.5:1 28s: 18s) and the absence of low molecular weight RNAs (degradation products). Control samples to detect genomic DNA contamination included RTQ-PCR reactions run in the absence of reverse transcriptase using probe and primer sets designed to amplify across the span of a single exon.

RNA samples were normalized in reference to nucleic acids encoding constitutively expressed genes (i.e., β-actin and GAPDH). Alternatively, non-normalized RNA samples were converted to single strand cDNA (sscDNA) using Superscript II (Invitrogen Corporation, Carlsbad, CA, Catalog No. 18064-147) and random hexamers according to the manufacturer's instructions. Reactions containing up to 10 μg of total RNA in a volume of 20 μl or were scaled up to contain 50 μg of total RNA in a volume of 100 1 and were incubated for 60 minutes at 42°C. sscDNA samples were then normalized in reference to nucleic acids as described above.

Probes and primers were designed according to Applied Biosystems Primer Express Software package (version I for Apple Computer's Macintosh Power PC) or a similar algorithm using the target sequence as input. Default reaction condition settings and the following parameters were set before selecting primers: 250 nM primer concentration; 58°- 60° C primer melting temperature (T_m) range; 59° C primer optimal Tm; 2° C maximum primer difference (if probe does not have 5' G, probe T_m must be 10° C greater than primer T_m; and 75 bp to 100 bp amplicon size. The selected probes and primers were synthesized by Synthegen (Houston, TX). Probes were double purified by HPLC to remove uncoupled dye and evaluated by mass spectroscopy to verify coupling of reporter and quencher dyes to the 5' and 3' ends of the probe, respectively. Then final concentrations were: 900 nM forward and reverse primers, and 200nM probe.

Normalized RNA was spotted in individual wells of a 96 or 384- well PCR plate (Applied Biosystems, Foster City, CA). PCR cocktails included a single gene-specific probe and primers set or two multiplexed probe and primers sets. PCR reactions were done using TaqMan® One-Step RT-PCR Master Mix (Applied Biosystems, Catalog No. 4313803) following manufacturer's instructions. Reverse transcription was performed at 48° C for 30 minutes followed by amplification/PCR cycles: 95° C IO min, then 40 cycles at 95° C for 15 seconds, followed by 60° C for 1 minute. Results were recorded as CT values (cycle at which a given sample crosses a threshold level of fluorescence) and plotted using a log scale, with the difference in RNA concentration between a given sample and the sample with the lowest CT value being represented as 2 to the power of delta CT. The percent relative expression was the reciprocal of the RNA difference multiplied by 100. CT values below 28 indicate high expression, between 28 and 32 indicate moderate expression, between 32 and 35 indicate low expression and above 35 reflect levels of expression that were too low to be measured reliably.

Normalized sscDNA was analyzed by RTQ-PCR using IX TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions. PCR amplification and analysis were done as described above. Panels 1, 1.1, 1.2, and 1.3D

Panels 1, 1.1, 1.2 and 1.3D included 2 control wells (genomic DNA control and chemistry control) and 94 wells of cDNA samples from cultured cell lines and primary normal tissues. Cell lines were derived from carcinomas (ca) including: lung, small cell (s cell var), non small cell (non-s or non-sm); breast; melanoma; colon; prostate; glioma (glio), astrocytoma (astro) and neuroblastoma (neuro); squamous cell (squam); ovarian; liver; renal; gastric and pancreatic from the American Type Culture Collection (ATCC, Bethesda, MD). Normal tissues were obtained from individual adults or fetuses and included: adult and fetal skeletal muscle, adult and fetal heart, adult and fetal kidney, adult and fetal liver, adult and fetal lung, brain, spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. The following abbreviations are used in reporting the results: metastasis (met); pleural effusion (pi. eff or pi effusion) and * indicates established from metastasis.

GENERAL_SCREENING_PANEL_V1.4, V1.5, V1.6 AND 1.7

Panels 1.4, 1.5, 1.6 and 1.7 were as described for Panels 1, 1.1, 1.2 and 1.3D, above except that normal tissue samples were pooled from 2 to 5 different adults or fetuses.

Panels 2D, 2.2, 2.3, and 2.4

Panels 2D, 2.2, 2.3 and 2.4 included 2 control wells and 94 wells containing RNA or cDNA from human surgical specimens procured through the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI), Ardais (Lexington, MA) or Clinomics BioSciences (Frederick, MD). Tissues included human malignancies and in some cases matched adjacent normal tissue (NAT). Information regarding histopathological assessment of tumor differentiation grade as well as the clinical stage of the patient from which samples were obtained was generally available. Normal tissue RNA and cDNA samples were purchased from various commercial sources such as Clontech (Palo Alto, CA), Research Genetics and Invitrogen (Carlsbad, CA).

HASS PANEL V1.0

The HASS Panel vl.O included 93 cDNA samples and two controls including: 81 samples of cultured human cancer cell lines subjected to serum starvation, acidosis and anoxia according to established procedures for various lengths of time; 3 human primary cells; 9 malignant brain cancers (4 medulloblastomas and 5 glioblastomas); and 2 controls. Cancer cell lines (ATCC) were cultured using recommended conditions and included: breast, prostate, bladder, pancreatic and CNS. Primary human cells were obtained from Clonetics (Walkersville, MD). Malignant brain samples were gifts from the Henry Ford Cancer Center.

ARDAIS PANEL V1.0

The ARDAIS Panel vl .0 included 2 controls and 22 test samples including: human lung adenocarcinomas, lung squamous cell carcinomas, and in some cases matched adjacent normal tissues (NAT) obtained from Ardais. Unmatched malignant and non-malignant RNA samples from lungs with gross histopathological assessment of tumor differentiation grade and stage and clinical state of the patient were obtained from Ardais.

ARDAIS PROSTATE V1.0

ARDAIS Prostate vl.O panel included 2 controls and 68 test samples of human prostate malignancies and in some cases matched adjacent normal tissues (NAT) obtained from Ardais. RNA from unmatched malignant and non-malignant prostate samples with gross histopathological assessment of tumor differentiation grade and stage and clinical state of the patient were also obtained from Ardais.

ARDAIS KIDNEY Vl.O

ARDAIS Kidney vl.O panel included 2 control wells and 44 test samples of human renal cell carcinoma and in some cases matched adjacent normal tissue (NAT) obtained from Ardais. RNA from unmatched renal cell carcinoma and normal tissue with gross histopathological assessment of tumor differentiation grade and stage and clinical state of the patient were also obtained from Ardais.

PANELS 3D, 3.1 AND 3.2

Panels 3D, 3.1, and 3.2 included two controls, 92 cDNA samples of cultured human cancer cell lines and 2 samples of human primary cerebellum. Cell lines (ATCC, National Cancer Institute (NCI), German tumor cell bank) were cultured as recommended and were derived from: squamous cell carcinoma of the tongue, melanoma, sarcoma, leukemia, lymphoma, and epidermoid, bladder, pancreas, kidney, breast, prostate, ovary, uterus, cervix, stomach, colon, lung and CNS carcinomas. Panels 4D, 4R, and 4.1D

Panels 4D, 4R, and 4. ID included 2 control wells and 94 test samples of RNA (Panel 4R) or cDNA (Panels 4D and 4. ID) from human cell lines or tissues related to inflammatory conditions. Controls included total RNA from normal tissues such as colon, lung (Stratagene, La Jolla, CA), thymus and kidney (Clontech, Palo Alto, CA). Total RNA from cirrhotic and lupus kidney was obtained from BioChain Institute, Inc., (Hayward, CA). Crohn's intestinal and ulcerative colitis samples were obtained from the National Disease Research Interchange (NDRI, Philadelphia, PA). Cells purchased from Clonetics (Walkersville, MD) included: astrocytes, lung fibroblasts, dermal fibroblasts, coronary artery smooth muscle cells, small airway epithelium, bronchial epithelium, microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells, and human umbilical vein endothelial. These primary cell types were activated by incubating with various cytokines (IL-1 beta -1-5 ng/ml, TNF alpha -5-10 ng/ml, IFN gamma -20-50 ng/ml, IL-4 -5-10 ng/ml, IL-9 -5-10 ng/ml, IL-13 5-10 ng/ml) or combinations of cytokines as indicated. Starved endothelial cells were cultured in the basal media (Clonetics, Walkersville, MD) with 0.1% serum.

Mononuclear cells were prepared from blood donations using Ficoll. LAK cells were cultured in culture media [DMEM, 5% FCS (Hyclone, Logan, UT), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, MD), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x 10^"5 M (Gibco), and 10 mM Hepes (Gibco)] and interleukin 2 for 4-6 days. Cells were activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, 5-10 ng/ml IL- 12, 20-50 ng/ml IFN gamma or 5-10 ng/ml IL-18 for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in culture media with -5 μg/ml PHA (phytohemagglutinin) or PWM (pokeweed mitogen; Sigma-Aldrich Corp., St. Louis, MO). Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing them 1:1 at a final concentration of -2x10⁶ cells/ml in culture media. The MLR samples were taken at various time points from 1- 7 days for RNA preparation.

Monocytes were isolated from mononuclear cells using CD 14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet (Miltenyi Biotec, Auburn, CA) according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culturing in culture media with 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culturing monocytes for 5-7 days in culture media with -50 ng/ml 10% type AB Human Serum (Life technologies, Rockville, MD) or MCSF (Macrophage colony stimulating factor; R&D, Minneapolis, MN). Monocytes, macrophages and dendritic cells were stimulated for 6 or 12-14 hours with 100 ng/ml lipopolysaccharide (LPS). Dendritic cells were also stimulated with 10 μg/ml anti-CD40 monoclonal antibody (Pharmingen, San Diego, CA) for 6 or 12-14 hours.

CD4+ lymphocytes, CD8+ lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positive VS selection columns and a Vario Magnet (Miltenyi Biotec, Auburn, CA) according to the manufacturer's instructions. CD45+RA and CD45+RO CD4+ lymphocytes were isolated by depleting mononuclear cells of CD8+, CD56+, CD14+ and CD19+ cells using CD8, CD56, CD14 and CD 19 Miltenyi beads and positive selection. CD45RO Miltenyi beads were then used to separate the CD45+RO CD4+ lymphocytes from CD45+RA CD4+ lymphocytes. CD45+RA CD4+, CD45+RO CD4 +and CD8+ lymphocytes were cultured in culture media at 10⁶ cells/ml in culture plates precoated overnight with 0.5 μg/ml anti-CD28 (Pharmingen, San Diego, CA) and 3 Dg/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD 8+ lymphocytes, isolated CD8+ lymphocytes were activated for 4 days on anti-CD28, anti-CD3 coated plates and then harvested and expanded in culture media with IL-2 (1 ng/ml). These CD8+ cells were activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as described above. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. Isolated NK cells were cultured in culture media with 1 ng/ml IL-2 for 4-6 days before RNA was prepared.

B cells were prepared from minced and sieved tonsil tissue (NDRI). Tonsil cells were pelleted and resupended at 10⁶ cells/ml in culture media. Cells were activated using 5 μg/ml PWM (Sigma- Aldrich Corp., St. Louis, MO) or -10 μg/ml anti-CD40 (Pharmingen, San Diego, CA) and 5-10 ng/ml IL-4. Cells were harvested for RNA preparation after 24, 48 and 72 hours.

To prepare primary and secondary Thl/Th2 and Trl cells, umbilical cord blood CD4+ lymphocytes (Poietic Systems, German Town, MD) were cultured at 10⁵10 cells/ml in culture media with IL-2 (4 ng/ml) in 6- well Falcon plates (precoated overnight with 10 μg/ml anti-CD28 (Pharmingen) and 2 μg/ml anti-CD3 (OKT3; ATCC) then washed twice with PBS).

To stimulate Thi phenotype differentiation, IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used; for Th2 phenotype differentiation, IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used; and for Trl phenotype differentiation, IL-10 (5 ng/ml) was used. After 4-5 days, the activated Thi, Th2 and Trl lymphocytes were washed once with DMEM and expanded for 4-7 days in culture media with IL-2 (1 ng/ml). Activated Thi, Th2 and Trl lymphocytes were re-stimulated for 5 days with anti-CD28/CD3 and cytokines as described above with the addition of anti-CD95L (1 μg/ml) to prevent apoptosis. After 4-5 days, the Thi, Th2 and Trl lymphocytes were washed and expanded in culture media with IL-2 for 4-7 days. Activated Thi and Th2 lymphocytes were maintained for a maximum of three cycles. RNA was prepared from primary and secondary Thi, Th2 and Trl after 6 and 24 hours following the second and third activations with plate-bound anti-CD3 and anti-CD28 mAbs and 4 days into the second and third expansion cultures.

Leukocyte cells lines Ramos, EOL-1, KU-812 were obtained from the ATCC. EOL-1 cells were further differentiated by culturing in culture media at 5 xlO⁵ cells/ml with 0.1 mM dbcAMP for 8 days, changing the media every 3 days and adjusting the cell concentration to 5 xlO⁵ cells/ml. RNA was prepared from resting cells or cells activated with PMA (10 ng/ml) and ionomycin (1 μg/ml) for 6 and 14 hours. RNA was prepared from resting CCD 1106 keratinocyte cell line (ATCC) or from cells activated with -5 ng/ml TNF alpha and 1 ng/ml IL-1 beta. RNA was prepared from resting NCI-H292, airway epithelial tumor cell line (ATCC) or from cells activated for 6 and 14 hours in culture media with 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13, and 25 ng/ml IFN gamma.

RNA was prepared by lysing approximately 10⁷ cells/ml using Trizol (Gibco BRL) then adding 1/10 volume of bromochloropropane (Molecular Research Corporation, Cincinnati, OH), vortexing, incubating for 10 minutes at room temperature and then spinning at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was placed in a 15 ml Falcon Tube and an equal volume of isopropanol was added and left at -20° C overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water with 35 μl buffer (Promega, Madison, WI) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse and incubated at 37° C for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with 1/10 volume of 3 M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down, placed in RNAse free water and stored at -80° C. AI comprehensive panel vl.O

Autoimmunity (AI) comprehensive panel vl.O included two controls and 89 cDNA test samples isolated from male (M) and female (F) surgical and postmortem human tissues that were obtained from the Backus Hospital and Clinomics (Frederick, MD). Tissue samples included : normal, adjacent (Adj); matched normal adjacent (match control); joint tissues (synovial (Syn) fluid, synovium, bone and cartilage, osteoarthritis (OA), rheumatoid arthritis (RA)); psoriatic; ulcerative colitis colon; Crohns disease colon; and emphysmatic, asthmatic, allergic and chronic obstructive pulmonary disease (COPD) lung.

AI.05 chondrosarcoma

AI.05 chondrosarcoma plates included SW1353 cells (ATCC) subjected to serum starvation and treated for 6 and 18 h with cytokines that are known to induce MMP (1, 3 and 13) synthesis (e.g. ILlbeta). These treatments included: IL-lβ (10 ng/ml), IL-lβ + TNF-α (50 ng/ml), IL-lβ + Oncostatin (50 ng/ml) and PMA (100 ng/ml). Supernatants were collected and analyzed for MMP 1, 3 and 13 production. RNA was prepared from these samples using standard procedures.

Panels 5D and 51

Panel 5D and 51 included two controls and cDNAs isolated from human tissues, human pancreatic islets cells, cell lines, metabolic tissues obtained from patients enrolled in the Gestational Diabetes study (described below), and cells from different stages of adipocyte differentiation, including differentiated (AD), midway differentiated (AM), and undifferentiated (U; human mesenchymal stem cells).

Gestational Diabetes study subjects were young (18 - 40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. Uterine wall smooth muscle (UT), visceral (Vis) adipose, skeletal muscle (SK), placenta (PI) greater omentum adipose (GO Adipose) and subcutaneous (SubQ) adipose samples (<1 cc) were collected, rinsed in sterile saline, blotted and flash frozen in liquid nitrogen. Patients included: Patient 2, an overweight diabetic Hispanic not on insulin; Patient 7-9, obese non-diabetic Caucasians with body mass index (BMI) greater than 30; Patient 10, an overweight diabetic Hispanic, on insulin; Patient 11, an overweight nondiabetic African American; and Patient 12, a diabetic Hispanic on insulin. Differentiated adipocytes were obtained from induced donor progenitor cells (Clonetics, Walkersville, MD). Differentiated human mesenchymal stem cells (HuMSCs) were prepared as described in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr 2 1999: 143-147. mRNA was isolated and sscDNA was produced from Trizol lysates or frozen pellets. Human cell lines (ATCC, NCI or German tumor cell bank) included: kidney proximal convoluted tubule, uterine smooth muscle cells, small intestine, liver HepG2 cancer cells, heart primary stromal cells and adrenal cortical adenoma cells. Cells were cultured, RNA extracted and sscDNA was produced using standard procedures

Panel 51 also contains pancreatic islets (Diabetes Research Institute at the University of Miami School of Medicine).

Human Metabolic RTQ-PCR Panel

Human Metabolic RTQ-PCR Panel included two controls (genomic DNA control and chemistry control) and 211 cDNAs isolated from human tissues and cell lines relevant to metabolic diseases. This panel identifies genes that play a role in the etiology and pathogenesis of obesity and/or diabetes. Metabolic tissues including placenta (PI), uterine wall smooth muscle (Ut), visceral adipose, skeletal muscle (Sk) and subcutaneous (SubQ) adipose were obtained from the Gestational Diabetes study (described above). Included in the panel are: Patients 7 and 8, obese non-diabetic Caucasians; Patient 12 a diabetic Caucasian with unknown BMI, on insulin (treated); Patient 13, an overweight diabetic Caucasian, not on insulin (untreated); Patient 15, an obese, untreated, diabetic Caucasian; Patient 17 and 25, untreated diabetic Caucasians of normal weight; Patient 18, an obese, untreated, diabetic Hispanic; Patient 19, a non-diabetic Caucasian of normal weight; Patient 20, an overweight, treated diabetic Caucasian; Patient 21 and 23, overweight non-diabetic Caucasians; Patient 22, a treated diabetic Caucasian of normal weight; Patient 23, an overweight non-diabetic Caucasian; and Patients 26 and 27, obese , treated, diabetic Caucasians.

Total RNA was isolated from metabolic tissues including: hypothalamus, liver, pancreas, pancreatic islets, small intestine, psoas muscle, diaphragm muscle, visceral (Vis) adipose, subcutaneous (SubQ) adipose and greater omentum (Go) from 12 Type II diabetic (Diab) patients and 12 non diabetic (Norm) at autopsy. Control diabetic and non-diabetic subjects were matched where possible for: age; sex, male (M); female (F); ethnicity, Caucasian (CC); Hispanic (HI); African American (AA); Asian (AS); and BMI, 20-25 (Low BM), 26-30 (Med BM) or overweight (Overwt), BMI greater than 30 (Hi BMI) (obese). RNA was extracted and ss cDNA was produced from cell lines (ATCC) by standard methods.

CNS Panels

CNS Panels CNSD.01, CNS Neurodegeneration Vl.O and CNS Neurodegeneration V2.0 included two controls and 46 to 94 test cDNA samples isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital). Brains were removed from calvaria of donors between 4 and 24 hours after death, and frozen at -80°C in liquid nitrogen vapor.

Panel CNSD.01

Panel CNSD.01 included two specimens each from: Alzheimer's disease, Parkinson's disease, Huntington's disease, Progressive Supemuclear Palsy (PSP), Depression, and normal controls. Collected tissues included: cingulate gyrus (Cing Gyr), temporal pole (Temp Pole), globus palladus (Glob palladus), substantia nigra (Sub Nigra), primary motor strip (Brodman Area 4), parietal cortex (Brodman Area 7), prefrontal cortex (Brodman Area 9), and occipital cortex (Brodman area 17). Not all brain regions are represented in all cases.

Panel CNS Neurodegeneration Vl.O

The CNS Neurodegeneration Vl.O panel included: six Alzheimer's disease (AD) brains and eight normals which included no dementia and no Alzheimer's like pathology (control) or no dementia but evidence of severe Alzheimer's like pathology (Control Path), specifically senile plaque load rated as level 3 on a scale of 0-3; 0 no evidence of plaques, 3 severe AD senile plaque load. Tissues collected included: hippocampus, temporal cortex (Brodman Area 21), parietal cortex (Brodman area 7), occipital cortex (Brodman area 17) superior temporal cortex (Sup Temporal Ctx) and inferior temporal cortex (Inf Temproal Ctx).

Gene expression was analyzed after normalization using a scaling factor calculated by subtracting the Well mean (CT average for the specific tissue) from the Grand mean (average CT value for all wells across all runs). The scaled CT value is the result of the raw CT value plus the scaling factor.

Panel CNS Neurodegeneration V2.0

The CNS Neurodegeneration V2.0 panel included sixteen cases of Alzheimer's disease (AD) and twenty-nine normal controls (no evidence of dementia prior to death) including fourteen controls (Control) with no dementia and no Alzheimer's like pathology and fifteen controls with no dementia but evidence of severe Alzheimer's like pathology (AH3), specifically senile plaque load rated as level 3 on a scale of 0-3; 0 no evidence of plaques, 3 severe AD senile plaque load. Tissues from the temporal cortex (Brodman Area 21) included the inferior and superior temporal cortex that was pooled from a given individual (Inf & Sup Temp Ctx Pool). A. CG103910-02: BMP7.

Expression of gene CGI 03910-02 was assessed using the primer-probe set Ag7249, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB and AC.

Table AA. Probe Name Ag7249

Table AB. General_screening_panel_vl.7

Table AC. Panel 4. ID

General_screeningjpanel_vl.7 Summary: Ag7249 Highest expression of this gene was detected in ovarian cancer cell line IGROV-1 (CT=28.8) and moderate expression was detected in cancer cell lines derived from melanoma, ovarian, lung, breast, colon and brain cancers. CG103910-02 gene expression is a marker of cancer vs normal tissue and is useful to detect cancers. Therapeutic modulation of this gene, expressed protein and/or the use of antibodies or small molecule drugs targeting this gene or gene product are useful in the treatment of melanoma, ovarian, lung, breast, colon and brain cancers. Gene expression was detected at low levels in certain regions of the central nervous system examined including: amygdala, hippocampus, thalamus, cerebellum, cerebral cortex, and spinal cord. Therapeutic modulation of this gene product is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Gene expression was detected at low levels in thyroid, fetal heart, kidney, and trachea.

Panel 4.1D Summary: Ag7249 Low expression of this gene was detected in activated Ramos B cells (CT=34.4). Lower but significant gene expression was detected in untreated Ramos B cells. B cells contribute to the immune response through various functional roles, including antibody production and are implicated in the production of auto-antibodies against self-antigens in autoimmune disorders. Therapeutic modulation of this gene, encoded protein and/or antibodies or small molecule drugs that antagonize its function reduce or eliminate the symptoms of patients suffering from asthma, allergies, chronic obstructive pulmonary disease, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, osteoarthritis, systemic lupus erythematosus and other autoimmune disorders.

B. CG103910-03: BMP7.

Expression of gene CG103910-03 was assessed using the primer-probe set Ag7250, described in Table BA. Results of the RTQ-PCR runs are shown in Tables BB, BC and BD.

Table BA. Probe Name Ag7250

Table BB. AI.05 chondrosarcoma

Table BC. General_screening_panel_vl.7

Table BD. Panel 4. ID

AI.05 chondrosarcoma Summary: Ag7250 Highest CG103910-03 gene expression was detected in activated chondrosarcoma cell line (CT=28.4). Gene expression was upregulated upon IL-1 treatment, a potent activator of pro-inflammatory cytokines and matrix metalloproteinases which participate in the destruction of cartilage observed in Osteoarthritis (OA). Modulation of gene expression or its encoded protein and/or the use of antibodies, small molecules or antisense targeting the gene or the encoded protein are important for preventing the degeneration of cartilage observed in OA.

General_screening_panel_vl.7 Summary: Ag7250 Highest gene expression was detected in ovarian cancer OVCAR cell line (CT=22.6). High gene expression was detected in cancer cell lines derived from melanoma, ovarian, lung, breast, colon and brain cancers. CG 103910- 03 gene expression is a marker useful to differentiate these cancers and to detect their presence in vitro and in vivo. Therapeutic modulation of this gene or encoded protein and/or use of antibodies or small molecule drug targeting the gene or the encoded protein is useful in the treatment of melanoma, ovarian, lung, breast, colon and brain cancers. Gene expression was high in all the regions of the central nervous system examined including: amygdala, hippocampus, thalamus, cerebellum, substantia nigra, cerebral cortex, and spinal cord. Therapeutic modulation of this gene or the encoded protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Among tissues with metabolic or endocrine function, gene expression was moderate in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, fetal liver and the gastrointestinal tract. Therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

Panel 4.1D Summary: Ag7250 Highest gene expression was detected in activated Ramos B cells (CT=28.4) with significant expression also detected in untreated Ramos B cells. B cells contribute to the immune response through various functional roles, including antibody production and are implicated in the production of auto-antibodies against self-antigens in autoimmune disorders. Therapeutic modulation of this gene, encoded protein and/or antibodies or small molecule drugs that antagonize its function reduce or eliminate the symptoms of patients suffering from asthma, allergies, chronic obstructive pulmonary disease, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, osteoarthritis, systemic lupus erythematosus and other autoimmune disorders.

C. CG183860-01: Novel Membrane Protein.

Expression of gene CG183860-01 was assessed using the primer-probe set Ag6837, described in Table CA. Results of the RTQ-PCR runs are shown in Tables CB, CC and CD. Table CA. Probe Name Ag6837

Table CB. CNS_neurodegeneration_vl .0

Table CC. General_screening_panel_vl.6

Table CD. Panel 4. ID

EOL-1 dbcAMP j 0.0 (Dermal fibroblast CCD 1070 IL-1 beta 0.0

EOL-1 dbcAMP PMA/ionomycin 10.0 |Dermal fibroblast IFΝ gamma 0.0

Dendritic cells none j 0.0 (Dermal fibroblast IL-4 2.2

Dendritic cells LPS 10.0 JDermal Fibroblasts rest 0.0

Dendritic cells anti-CD40 j 0.0 (Neutrophils TNFa+LPS 0.0

Monocytes rest 0.0 jNeutrophils rest 0.0

Monocytes LPS j O.o jColon 2.8

Macrophages rest j 0.0 (Lung 3.7

Macrophages LPS J 0.0 JThymus 0.0

HUNEC none |57.θ(Kidney 100.0

HUNEC starved J42 9J

CNS_neurodegeneration_vl.0 Summary: Ag6837 Highest CGI 83860 gene expression was detected in the hippocampus of an Alzheimer's patient (CT=31) and was also determined to be upregulated in the temporal cortex of Alzheimer's disease patients. Therapeutic modulation of the expression or function of this gene, encoded protein and/or use of antibodies or small molecule drug targeting the encoded protein to decrease neuronal cell death is useful in the treatment of this disease.

General_screening_panel_vl.6 Summary: Ag6837 Highest gene expression was detected in a prostate cancer cell line (CT=24.5) and high levels of expression were also seen in ovarian and brain cancer cell lines. CGI 83860 gene expression is a marker for differentiating cancerous from normal tissues and to detect the presence of these cancers. Therapeutic modulation of the expression or function of this gene, encoded protein and/or use of antibodies or small molecule drug targeting the encoded protein are effective in the treatment of cancer. Gene expression was also detected at higher levels in fetal kidney and lung (CTs=27-29) relative to expression in the corresponding adult tissues (CTs=32-33). The relative over expression of this gene in these fetal tissues suggests that the protein product may enhance lung and kidney growth or development in the fetus and are useful in a regenerative capacity in the adult.

Panel 4.1D Summary: Ag6837 Highest expression was seen in kidney (CT=32.7). Low but significant gene expression was detected in samples derived from human endothelium cells from umbilical vein and pulmonary artery (HUVEC and HPAEC). Therapeutic modulation of this gene, encoded protein and/or antibodies, small molecule drug targeting the encoded protein will reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases that involve endothelial cells, such as lupus erythematosus, asthma, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, osteoarthritis, and psoriasis. D. CG110590-02: SIMILAR TO CHORDIN-LIKE.

Expression of gene CGI 10590-02 was assessed using the primer-probe set Ag7182, described in Table DA. Results of the RTQ-PCR runs are shown in Table DB.

Table DA. Probe Name Ag7182

Table DB. General_screening_panel_vl.7

General_screeningjpanel_vl.7 Summary: Ag7182 Highest CGI 10590 gene expression was seen in adipose (CT=31.9). Therapeutic modulation of this gene and encoded protein is useful in the treatment of adipose related diseases such as obesity and diabetes. Low gene expression was seen in fetal and adult brain. Therapeutic modulation of this gene and/or encoded protein is useful in the treatment of neurological disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

E. CG184416-01: metalloprotease mmp21/22C.

Expression of gene CGI 84416-01 was assessed using the primer-probe set Ag7014, described in Table EA. Results of the RTQ-PCR runs are shown in Table EB.

Table EA. Probe Name Ag7014

Table EB. General_screening_panel_vl.6

General_screening_panel_vl.6 Summary: Ag7014 Highest gene expression was detected in an ovarian cancer cell line (CT=29.8), with low but significant expression in a prostate cancer cell line. Gene expression level is a marker of ovarian and prostate cancer tissue and for detecting the presence of these cancers in vitro or in vivo.

F. CG50513-01: Tumor-related protein (PDRC1).

Expression of gene CG50513-01 was assessed using the primer-probe sets Ag2752 and Ag5, described in Tables FA and FB. Results of the RTQ-PCR runs are shown in Tables FC, FD, FE and FF.

Table FA. Probe Name Ag2752

Table FB. Probe Name Ag5

Start SEQ ID

Primers Sequences Length Position No

Forward 5 ' -gtgatcctcaggctggacca-3 ' 20 1219 367

TET-5 ' -ccagtgtttcctcagcacagggcc-3 ' ^■

Probe TAMRA 24 1253 368

Reverse 5 ' -ttctgactgggctgcatcc-3 ' 19 1278 369 Table FC. Panel 1

Table FE. Panel 2D

Table FF. Panel 4D

Column A - Rel. Exp.(%) Ag2752, Run 162015236

Tissue Name Tissue Name

Secondary Thi act 0.0; HUVEC IL-lbeta 0.0

Secondary Th2 act 0.0 [HUVEC IFN gamma 0.0

Secondary Trl act O.O HUVEC TNF alpha + IFN gamma 0.0

Secondary Thi rest 0.0 HUVEC TNF alpha + IL4 0.0

Secondary Th2 rest 0.0 HUVEC IL-11 0.0

Panel 1 Summary: Ag5 Highest CG50513-01 gene expression was seen in trachea (CT=25.2) with low to moderate expression detected in normal tissues including: testis, colon, thymus, skeletal muscle, spinal cord, pituitary gland, salivary gland, thyroid, and adrenal gland. Therefore, therapeutic modulation of this gene, encoded protein and/or antibodies, small molecule drug targeting the protein are useful in the treatment of the diseases associated with these tissues including obesity, diabetes, fertility and hypogonadism. Low gene expression was also seen in breast, lung and brain cancer cell lines. Gene expression level is a marker of these cancer tissues and for detecting the presence of these cancers in vitro or in vivo. Therapeutic modulation of this gene gene, encoded protein and/or antibodies, small molecule drug targeting the protein is useful in the treatment of these cancers.

Panel 2D Summary: Ag2752 Highest gene expression was seen in normal prostate (CT=31.4) and significant expression was also seen in normal prostate and thyroid compared to cancer samples. Therapeutic modulation of this gene and/or encoded protein that increases the activity of this gene and the encoded protein are useful in the treatment of prostate and thyroid cancers.

Low gene expression was also detected in lung cancer which was higher than expression in normal lung. Therefore, expression level of this gene will be useful as marker to detect the presence of lung cancer and therapeutic modulation of this gene, encoded protein is useful in the treatment of lung cancer.

Panel 4D Summary: Ag2752 Significant gene expression was detected in resting and activated small airway epithelium (CTs=31.5) and modulation of the expression or activity of this gene and/or the protein encoded by it is useful in the treatment of asthma, COPD, and emphysema.

G. CG50949-03: MEMBRANE-TYPE MOSAIC SERINE PROTEASE.

Expression of gene CG50949-03 was assessed using the primer-probe sets Ag020b, Ag20 and Ag5238, described in Tables GA, GB and GC. Results of the RTQ-PCR runs are shown in Tables GD, GE and GF. Table GA. Probe Name Ag020b

Table GB. Probe Name Ag20

Table GC. Probe Name Ag5238

Table GD. General_screening_panel_vl.5

Table GE. General_screening_panel_vl.6 j Column A ■ - Rel. Exp.(%) Ag20, Run 277226634 j Tissue Name j A J Tissue Name | A jAdipose j 0.2 (Renal ca. TK-10 0.1

(Melanoma* Hs688(A).T j 0.0 (Bladder 3.9

(Melanoma* Hs688(B).T j 0.0 (Gastric ca. (liver met.) NCI-N87 42.3

(Melanoma* Ml 4 | 9.4 (Gastric ca. KATO III 1.5

(Melanoma* LOXIMVI j 0.4 jColon ca. SW-948 0.5

(Melanoma* SK-MEL-5 j 0.8 (Colon ca. SW480 0.6 Table GF. Panel 4. ID

General_screeningjpanel_vl.5 Summary: Ag5238 Highest gene expression was detected in T47D breast cancer cell line (CT=32.7) and low expression was also seen in melanoma, lung, gastric, and breast cancers cell lines. Expression level is a useful marker to differentiate these cancers from normal tissues and to detect the presence of these cancers in vitro or in vivo.

General_screeningjpanel_vl.6 Summary: Ag20 Highest gene expression was detected in T47D breast cancer cell line (CT=26). Moderate to low expression was also seen in melanoma, lung, colon, renal, pancreatic, renal, brain, gastric, and breast cancers cell lines. Expression is a useful marker to differentiate these cancers from normal tissues and to detect the presence of these cancers in vitro or in vivo.

Among tissues with metabolic or endocrine function, this gene was expressed at moderate to low levels in pancreas, adipose, thyroid, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene was expressed at low levels in most regions of the central nervous system examined including: amygdala, hippocampus, thalamus, cerebellum, and spinal cord. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

Panel 4.1D Summary: Ag20 Highest expression of this gene was seen in resting NCI-H292 cells (CT=30) with significant expression also detected in activated NCI-H292 cells, small airway epithelium, activated monocytes and macrophages, dendritic cells, and resting IL2 treated NK cells. Therefore, modulation of this gene and/or expressed protein with a functional therapeutic will alter the functions associated with these cell types and will relieve the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis. Ag5238 Highest expression using this probe-primer set was detected in activated macrophages (CT=33). Low gene expression was also seen in resting monocytes, keratinocytes and lung. Therefore, therapeutics modulation of this gene and/or expressed protein is important for the treatment of asthma, emphysema, inflammatory bowel disease, arthritis and psoriasis.

H. CG50949-05 and CG50949-06: MOSAIC SERINE PROTEASE.

Expression of gene CG50949-05 and CG50949-06 was assessed using the primer- probe sets Ag020b, Ag20 and Ag5241, described in Tables HA, HB and HC. Results of the RTQ-PCR runs are shown in Tables HD, HE and HF.

Table HA. Probe Name Ag020b

Table HB. Probe Name Ag20

Table HC. Probe Name Ag5241

Table HD. General_screeningjpanel_vl.5

Table HE. General_screening_panel_vl.6

Table HF. Panel 4.1D

Macrophages rest 3.2 0.0 Lung 3.1 0.0

Macrophages LPS 10.4 28.1 Thymus 0.0 0.0

HUVEC none 0.4 0.0 Kidney 4.5 3.4

HUVEC starved 2.8 0.0

General_screening_panel_vl.5 Summary: Ag5241 Highest gene expression was detected in T47D breast cancer cell line (CT=30.6) and moderate to low gene expression was detected in melanoma, colon, gastric, gastric, ovarian and breast cancer cell lines. CG50959 gene expression level is a useful marker to differentiate these cancers from normal tissues and to detect the presence of these cancers in vitro or in vivo. Furthermore, therapeutic modulation of this gene is useful in the treatment of these cancers.

Low gene expression was detected in fetal lung and brain. The relative over- expression in fetal tissue indicates that the expressed protein enhances lung and brain growth or development and acts in a regenerative capacity in the adult..

General_screening_panel_vl.6 Summary: Ag20 Highest expression of this gene was detected in T47D breast cancer cell line (CT=26) and moderate to low gene expression was also detected in melanoma, lung, colon, renal, pancreatic, renal, brain, gastric, and breast cancer cell lines. Expression level is a useful marker for differentiating these cancers from normal tissues and to detect the presence of these cancers. Among tissues with metabolic or endocrine function, this gene was expressed at moderate to low levels in pancreas, adipose, thyroid, fetal liver and gastrointestinal tract. Therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. Low gene expression levels was detected in the central nervous system including: amygdala, hippocampus, thalamus, cerebellum, and spinal cord. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in the diagnosis and/or treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

Panel 4.1D Summary: Ag20 Highest gene expression was seen in resting NCI-H292 (CT=30) and significant expression was detected in activated NCI-H292 cells, small airway epithelium, activated monocytes and macrophages, dendritic cells, and resting IL2 treated NK cells. Ag5241 Highest gene expression using this probe-primer set was detected in LPS activated monocytes (CT=33). Upon activation with pathogens such as LPS, monocytes contribute to innate and specific immunity by migrating to the site of tissue injury and releasing inflammatory cytokines. Modulation of gene expression and/or encoded protein prevents the recruitment of monocytes and the initiation of the inflammatory process, and relieves the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, rheumatoid arthritis, or osteoarthritis.

I. CG51018-01: Matrilin-2 precursor.

Expression of gene CG51018-01 was assessed using the primer-probe set Ag2764, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB, IC, ID and IE.

Table LA. Probe Name Ag2764

Table IB. CNS_neurodegeneration_vl.0

Table ID. Panel 2D

Table IE. Panel 5 Islet

CNS_neurodegeneration_vl.O Summary: Ag2764 This gene, a homolog of matrilin-2, is an intercellular matrix protein. The results of this panel shows expression in the brain. Glial scarring is a major inhibitor of CNS repair/regeneration involving intra and extra-cellular proteins. Reduction of expression levels of this gene or protein encoded by this gene decreases glial scarring in response to CNS injury, and promotes healing in spinal cord and/or brain trauma.

Panel 1.3D Summary: Ag2764 High gene expressed was detected in the thyroid gland (CT = 26.2), fetal kidney and fetal skeletal muscle (CTs = 27.1) and shows an association with normal tissue when compared to cancer cell lines. This gene was moderately expressed in pancreas, adrenal and pituitary glands, adipose, fetal and adult heart, fetal and adult liver, and adult skeletal muscle. The relative over expression of this gene in fetal skeletal muscle relative to adult skeletal muscle indicates that the protein product enhances muscular growth or development and acts in a regenerative capacity in the adult. Modulation of gene expression is useful in treatment of muscle related diseases treatment of weak or dystrophic muscle with the encoded protein restores muscle mass or function.

This gene is expressed in many tissues of the central nervous system including: amygdala, cerebellum, hippocampus, substantia nigra, thalamus, cerebral cortex, spinal cord, and the developing brain.

Panel 2D Summary: Ag2764 Highest gene expression was detected in normal thyroid tissue (CT = 24.7) and there was a strong association of gene expression in normal prostate tissue (CT = 25). This gene was overexpressed in normal thyroid tissue relative to samples derived from matched thyroid cancer tissue. Thus, therapeutic modulation of the activity or expression of this gene, encoded protein, and/or antibodies, small molecule drugs targeting the encoded protein is an effective treatment of thyroid and prostate cancers.

Panel 5 Islet Summary: Ag2764 Highest expression of this gene was seen in uterus of a non-diabetic but overweight patient (CT=25.9). High gene expression was seen in uterus, adipose, skeletal muscle, placenta, kidney and small intestine and moderate expression was seen in islet cells. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of metabolic/endocrine diseases including obesity and diabetes. J. CG51051-07 and CG51051-09: Netrin G1D like.

Expression of gene CG51051-07 and CG51051-09 was assessed using the primer- probe sets Ag290 and Ag040, described in Tables JA and JB. Results of the RTQ-PCR runs are shown in Tables JC and JD.

Table JA. Probe Name Ag290

Table JB. Probe Name Ag040

Start SEQ ID

Primers Sequences Length! Position No

Forward 15 ' -ggcacgtccctccgttct-3 ' 18 1292 394

TET-5 ' -ctgcgacaacgagctcctgcactg-

Probe ITAMRA 24 1266 395

Reverse i 5 ' -ctgttcaagttgcaaaccacaag-3 23 1232 396

Table JC. CNS_neurodegeneration_vl.O

Column A - Rel. Exp.(%) Ag040, Run 206975031 Column B - Rel. Exp.(%) Ag040, Run 269217520

Tissue Name B Tissue Name B

AD 1 Hippo 2.3 4.2 [Control (Path) 3 Temporal Ctx 2.2 j 5.3

AD 2 Hippo 18.6 38.7 Control (Path) 4 Temporal Ctx 16.3 23.2

AD 3 Hippo 1.4 4.0 AD 1 Occipital Ctx ^"gijlgj?

AD 4 Hippo 5.7 8.3 AD 2 Occipital Ctx (Missing) 0.0 0.0

AD 5 hippo 100.0 100.0 AD 3 Occipital Ctx 2.7 3.2

AD 6 Hippo 4.9 J 14.2 AD 4 Occipital Ctx 6.9 14.9

Table JP. Panel 1

CNS_neurodegeneration_vl.0 Summary: Ag040 This gene was downregulated in the temporal cortex of Alzheimer's diseased brain as analyzed by ANCOVA, with RNA quality as a covariate. This gene codes for Netrin like protein. Netrins are secreted proteins which have both neurotrophic and neuroprotective functions. They are believed to play a role in neurodevelopment, both in neuron survival and in axon guidance (Manitt C, Kennedy TE., 2002, Where the rubber meets the road: netrin expression and function in developing and adult nervous systems. Prog Brain Res. 137:425-42;PMID: 12440385). Therefore, up- regulation of this gene or its protein product, is useful preventing, treating or ameliorating symptoms associated with this disease.

Panel 1 Summary: Ag290 Highest gene expression was seen in thymus (CT=26). Indicating that this gene plays a role in T cell development. Targeting the encoded protein is useful for modulating immune function (T cell development) and is important for organ transplantation, AIDS treatment or post chemotherapy immune reconstitiution. Significant gene expression was seen in tissues with metabolic/endocrine function including pancreas, liver and gastrointestinal tract. Therapeutic gene and/or encoded protein modulation is useful in the treatment of metabolic/endocrine diseases including diabetes and obesity. High gene expression was detected in whole brain and cerebellum. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of neurological disorders such as ataxia, and autism.

K. CG51051-14: Netrin G1D like.

Expression of gene CG51051-14 was assessed using the primer-probe set Ag6679, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB, KC and KD.

Table KA. Probe Name Ag6679 jPrimersj Sequences JLengthjStart PositionjSEQ ID No

JForwardjδ ' -ccagtattggtacgaatgtctg-3 ' j 22 j 228 (397 jProbe JτET-5 ' -ctcctgcactgccagaacggag-3 ' -TAMRA )... ²?..., i 196 J398

JReverse j5 ' -acaggcagcgcacgt-3 ' 1 ¹⁵ I 166 J399

Table KB. CNS_neurodegeneration_vl.O

Table KC. General_screening_ρanel_vl.6

CNS_neurodegeneration_vl.0 Summary: Ag6679 This gene was dowmegulated in the temporal cortex of Alzheimer's diseased brain as analyzed by ANCOVA, with RNA quality as a covariate. This gene codes for Netrin like protein. Netrins are secreted proteins which have both neurotrophic and neuroprotective functions. They are believed to play a role in neurodevelopment, both in neuron survival and in axon guidance (Manitt C, Kennedy TE., 2002, Where the rubber meets the road: netrin expression and function in developing and adult nervous systems. Prog Brain Res. 137:425-42;PMID: 12440385). Therefore, up- regulation of this gene or its protein product, is useful preventing, treating or ameliorating symptoms associated with this disease. General_screening__panel_vl.6 Summary: Ag6679 Highest CG51051-14 gene expression was seen in U-118-MG brain cancer cell line (CT=28.1) and moderate to low gene expression was detected in melanoma, ovarian, breast, lung, renal and brain cancer cell lines. Gene expression is a marker of melanoma, ovarian, breast, and lung cancer useful in differentiating these tissues from normal tissues and detection of these cancers in vitro or in vivo. Therapeutic modulation of this gene, expressed protein is useful in the treatment of melanoma, ovarian, breast, lung, renal and brain cancers. Moderate to low gene expression was detected in tissues with metabolic or endocrine function such as: adipose, adrenal gland, pituitary gland, and fetal skeletal muscle. Modulation of gene activity is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. Significant gene expression was detected in central nervous system tissues including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

Panel 4.1D Summary: Ag6679 Highest gene expression was seen in kidney (CT=32.6). and low gene expression was seen in resting and activated dermal fibroblasts. Therefore, therapeutic modulation of this gene, its encoded protein is useful in the treatment of kidney and skin-related disorders such as lupus, glomerulonephritis and psoriasis.

L. CG52261-01: 3277237.

Expression of gene CG52261-01 was assessed using the primer-probe sets Ag2653 and Ag044, described in Tables LA and LB. Results of the RTQ-PCR runs are shown in Tables LC, LD, LE, LF and LG.

Table LA. Probe Name Ag2653

Probe TET-5 ' -tcctgacccacgcagtccataagga- TAMRA 25 777 404

Reverse 5 ' -tctgtgccccgtccaaa-3 ' 17 759 405

Table LC. Panel 1

Table LD. Panel 1.3D

Table LE. Panel 2.2

Table LG. Panel 5 Islet

Panel 1 Summary: Ag044 Highest CG52261 gene expression was seen in cerebellum (CT=28) and moderate expression was detected in central nervous system tissues including: ' amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Modulation of this gene and expressed protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Signigficant gene expression was also seen in fetal lung and two lung cancer cell lines indicating that gene expression level is useful as a marker to differentiate and detect the presence of lung cancer. Furthermore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of the lung cancer. Low expression of this gene was also seen in testis, thymus and heart.

Panel 1.3D Summary: Ag2653 Highest CG52261 gene expression was detected in fetal brain (CT=28.8) and moderate gene expression was seen in central nervous system tissues including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene and expressed protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Significant gene expression was also seen in brain, lung, colon and breast cancer cell lines. Expression levels of this gene are useful markers to detect the presence of these cancers. Modulation of this gene and/or encoded protein is useful in the treatment of the brain, lung, colon and breast cancers. This gene is expressed at moderate levels in tissues with metabolic or endocrine function including: adipose, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

Panel 2.2 Summary: Ag2653 Highest CG52261 gene expression was detected in normal lung (CT=30) and significant expression of this gene was seen in normal lung, colon, breast, ovary, kidney, uterus and stomach tissues collected from tumor margins compared to low gene expression detected in breast, thyroid, kidney, lung, ovary and colon cancer samples. Therefore, modulation of this gene, encoded protein and/or use of agonist targeting the encoded protein is useful in the treatment of these lung, colon, breast, ovary, kidney, uterus and stomach cancers.

Panel 4D Summary: Ag2653 Highest expression of this gene was seen in kidney (CT=28.6) and moderate to low expression was detected in activated and resting primary Thi, Trl, Th2 and secondary Thi cells, activated LAK cells, activated PBMC cells, activated B lymphocytes, endothelial cells, activated small airway epithelium, coronery artery SMC cells, astrocytes, NCI-H292 cells, activated lung, dermal fibroblasts, IBD colitis and Crohn's samples. Significant expression was seen in normal colon, thymus and lung tissues. Modulation of this gene, expressed protein and/or use of antibodies, small molecule drug targeting the encoded protein alter functions associated with these cell types and relief of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

Panel 5 Islet Summary: Ag2653 Highest expression of this gene was seen in adipose tissue from a diabetic patient (CT=32.6). Significant gene expression was seen in adipose, and skeletal muscle from either diabetic or non-diabetic but overweight patients. Low expression was seen in small intestine. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in treatment of metabolic diseases such as obesity and diabetes.

M. CG52414-02: Rhomboid.

Expression of gene CG52414-02 was assessed using the primer-probe sets Ag2648, Ag2786 and Ag7066, described in Tables MA, MB and MC. Results of the RTQ-PCR runs are shown in Tables MD, ME, MF, MG and MH.

Table MA. Probe Name Ag2648

Table MB. Probe Name Ag2786

Table MC. Probe Name Ag7066

Probe TET-5 ' -aggcctcactgtcccagagcatc-3 ' TAMRA 23 582 413

Reverse 5 ' -tccaaaccactgggctg-3 ' 17 615 414

Table MD. General_screening panel_vl.7

Table ME. Oncology_cell_line_screening_panel_v3.2

Table MF. Panel 1.3D

Column A ■ ■ Rel. Exp.(%) Ag2648, Run 156606391 Column B - ■ Rel. Exp.(%) Ag2786, Run 165527181

Tissue Name ... ! A J .^B ! Tissue Name A 1 B

Liver adenocarcinoma 20.9 j 16.5 Kidney (fetal) 17.1 j 17.7

Pancreas ^: 10.3|l3.0 Renal ca. 786-0 11.3 j 19.3

Pancreatic ca. CAPAN 2 19.1 J13.0 Renal ca. A498 100.0 j 100.0

Adrenal gland j 14.5 j 18.2 Renal ca. RXF 393 18.7 j 73.2

Thyroid 15.2)13.8 Renal ca. ACHN 17.7 j 7.5

Salivary gland 6.2 j 7.9 Renal ca. UO-31 63.3 j 34.9

Pituitary gland 3.1 j 4.4 Renal ca. TK-10 49.3 j 24.7

Brain (fetal) 2.9 j 6.6 _j Liver 2.4 j 4.5

Brain (whole) 4.7 (18.6 Liver (fetal) 7.9 j 10.7

Brain (amygdala) Jl7.3|32.1 Liver ca. (hepatoblast) HepG2 35.4 j 20.9

Brain (cerebellum) 2.1 j 9.3 Lung 33.2 j 40.3

General_screening_panel_vl.7 Summary: Ag7066 Highest CG52414 gene expression was seen in OVCAR-4 ovarian cancer cell line (CT=25.6) and high expression was detected in pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, melanoma and brain cancer cell lines. Expression of this gene is a useful marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene is effective in the treatment of pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, melanoma and brain cancers. Among tissues with metabolic or endocrine function, this gene was expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene is moderately expressed in central nervous system tissues including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

Oncology_cell_line_screening_panel_v3.2 Summary: Ag2648 Highest expression of this gene was detected in SU86.86 pancreatic cancer cell line (CT=30) and moderate gene expression was seen in lung, bone marrow, epidermoid, vulva, bone, bladder, pancreatic, renal, B cells and T cells, leukemia, lymphoma, cervical, gastric, colon, lung and brain cancer cell lines.

Panel 1.3D Summary: Ag2648/Ag2786 Highest expression of this gene was detected in renal cancer A498 cell line (CTs=28-28.9 and moderate gene expression was seen in pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, melanoma and brain cancer cell lines. Thus, expression of this gene is a useful marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene is effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Among tissues with metabolic or endocrine function, moderate gene expression was detected in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene showed moderate to low levels of expression in central nervous system tissues including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Modulation of this gene and/or encoded protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

Panel 2D Summary: Ag2648/Ag2786 Highest expression of this gene was detected in bladder and kidney cancers (CTs=26.4-28) and high to moderate gene expression was detected in cancer and normal samples derived from colon, prostate, liver, lung, kidney, breast, thyroid, ovary and stomach. Expression of this gene was higher in cancer samples especially gastric, bladder, breast, kidney and colon cancer compared to adjacent normal tissues. Expression of this gene is a useful marker to differentiate cancerous from normal adjacent tissues and to detect the presence of these cancers in vitro or in vivo. This gene codes for a protease belonging to Rhomboid family known to activate growth factors ligands (Urban et al. Cell 2001 Oct 19; 107(2): 173-82). Therefore this gene likely plays a role in tumor cell proliferation and invasion, by activating growth factors like TGFalpha and EGF that mediates cell growth and invasion. Targeting CG52414-02 protein with a human monoclonal antibody to inhibit the activity of this protein has therapeutic effect on tumors, particularly colon, gastric, kidney, ovarian and bladder tumors.

Panel 4D Summary: Ag2648/Ag2786 Highest expression of this gene was detected in LPS activated macrophages and monocytes (CTs=27-28.5) and high to moderate expression levels were detected in cell types significant in the immune response. These cells include: T-cell, B- cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal colon, lung, thymus and kidney tissues. Expression of this gene is stimulated in activated endothelial cells, small airway epithelium and fibroblasts. The ubiquitous pattern of expression indicates that this gene product is involved in homeostatic processes. Modulation of the gene, expressed protein and/or antibodies, small molecule drug targeting the encoded protein alters the functions of these cell types and leads to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

N. CG52643-02: 4324229RS.

Expression of gene CG52643-02 was assessed using the primer-probe sets Ag2812, Ag2822, Ag861, AglO, AgOlOb and Ag550, described in Tables NA, NB, NC, ND, NE and NF. Results of the RTQ-PCR runs are shown in Tables NG, NH and NI.

Table NA. Probe Name Ag2812

Table NB. Probe Name Ag2822

Table NC. Probe Name Ag861

Table ND. Probe Name AglO

Table NE. Probe Name AgOlOb

Table NF. Probe Name Ag550

Table NG. Panel 1

Table NH. Panel 2D

Panel 1 Summary: AglO/AgOlOb Highest expression of this gene was seen in NCI-H460 lung cancer cell line and cerebellum (CTs 22-24). High expression of this gene was also seen in melanoma, ovarian, lung, colon and liver cancer cell lines. Expression level of this gene is useful as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of this gene and/or expressed protein is useful in the treatment of melanoma, ovarian, lung, colon and liver cancers. Among tissues with metabolic or endocrine function, this gene was expressed at moderate levels in pancreas, adrenal gland, skeletal muscle, and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene was expressed at moderate to high levels in all regions of the central nervous system examined including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

Panel 2D Summary: Ag2812/Ag2822 Highest expression of this gene was seen in breast cancer sample (CTs=28-30). Moderate to low expression of this gene was also seen in normal and cancer samples from lung, ovary, bladder, breast, kidney, and prostate. Expression of this gene was higher in bladder and breast cancer samples. Therefore, expression level of this gene is useful as a marker to detect the presence of cancer, especially bladder and breast cancer. Furthermore, therapeutic modulation of this gene and/or expressed protein is useful in the treatment of lung, ovary, bladder, breast, kidney, and prostate cancers. Higher expression of this gene was seen in kidney cancer relative to the corresponding normal sample. Thus, modulation of the expression of this gene and/or encoded protein is useful in the treatment of kidney cancer.

Panel 4D Summary: Agl0/Ag2812/Ag2822 Highest expression of this gene was seen in thymus and activated Ramos B cells (CTs=30-32). Significant expression of this gene was also seen in resting Ramos B cells, activated primary Th2 cells and kidney. Therefore, therapeutic modulation of this gene, encoded protein leads to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

O. CG53270-01 and CG53270-02:.

Expression of gene CG53270-01 and CG53270-02 was assessed using the primer- probe sets Agl536 and Agl589, described in Tables OA and OB. Results of the RTQ-PCR runs are shown in Tables OC, OD, OE and DF. CG53270-02 represents the full length physical clone for CG53270-01.

Table OA. Probe Name Agl536

Table OB. Probe Name Agl589

Start SEQ ID

Primers Sequences Length Position No

ForwardJ5 ' -aagaagtctgccaccaagct-3 ' 20 936 436

JProbe TET-5 '-cacagcctgagacaaaacccgagg- TA RA 24 985 437

Reverse 5 ' -cctggacatttgcattgct-3 ' 19 1013 438 Table OC. AI_comprehensive panel_vl.O

Table OD. Panel 1.2

Table OE. Panel 2D

Table OF. Panel 4D

AI_comprehensive panel_vl.0 Summary: Agl589 Highest expression of this gene was seen in an asthma sample (CT=30). Moderate levels of expression of this gene were detected in samples derived from normal and orthoarthitis bone and adjacent bone, cartilage, synovium and synovial fluid samples, rheumatoid arthritis bone and cartilage, normal lung, COPD lung, emphysema, atopic asthma, asthma, Crohn's disease (normal matched control and diseased), ulcerative colitis(normal matched control and diseased), and psoriasis (normal matched control and diseased). Therefore, therapeutic modulation of this gene and/or expressed protein ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis.

Panel 1.2 Summary: Agl536 Highest expression of this gene was detected in testis (CT=26.4). Therefore, antibody or small molecule therapies targeting encoded protein modulates testis function and is important in the treatment of diseases that affect the testis, including fertility and hypogonadism. Moderate to low expression of this gene was also detected in melanoma, pancreatic, brain, lung, breast, ovarian, renal, liver and colon cancer cell lines. Modulation of this gene and/or encoded protein is useful in the treatment of melanoma, pancreatic, brain, lung, breast, ovarian, renal, liver and colon cancers. Among tissues with metabolic or endocrine function, this gene was expressed at low levels in pancreas, adrenal gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene was expressed at low levels in regions of the central nervous system including: amygdala, hippocampus, thalamus, cerebellum, and cerebral cortex. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

Panel 2D Summary: Agl536/Agl589 Highest expression of this gene was detected in breast cancer and normal prostate samples (CTs=30-32). Significant expression of this gene was seen in normal and cancer samples from prostate, lung, kidney, breast, bladder. Therefore, therapeutic modulations of this gene and/or encoded protein is useful in the treatment of prostate, lung, kidney, breast, bladder cancers.

Panel 4D Summary: Agl536/Agl589 Highest expression of this gene was detected in activated small airway epithelium and IL-4 activated NCI-H292 (CTs=31-32). Moderate expression of this gene was also seen in resting keratinocytes, activated bronchial epithelium, resting and activated mucoepidermoid NCI-H292 cells, activated lung fibroblasts and liver cirrhosis sample. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of liver cirrhosis and inflammatory lung disorders that include chronic obstructive pulmonary disease, asthma, allergy and emphysema.

P. CG54254-04: LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN.

Expression of gene CG54254-04 was assessed using the primer-probe sets Agl48 and Ag201, described in Tables PA and PB. Results of the RTQ-PCR runs are shown in Tables PC, PD, PE, PF and PG.

Table PA. Probe Name Agl48

Table PB. Probe Name Ag201

Start SEQ ID

Primers! Sequences Length Position No

Table PC. CNS_neurodegeneration_vl.O

Table PP. Panel 1

Colon ca. HCT-15 J 5.3 JMelanoma* (met) Hs688(B).T 1.3

Colon ca. HCC-2998 j 4.9 |Melanoma UACC-62 1.3

Gastric ca. * (liver met) NCI-N87 j 13.4 (Melanoma M14 3.3

Bladder j 3.4 JMelanoma LOX IMVI 13.1

Trachea j 10.7 JMelanoma* (met) SK-MEL-5 1.3

Kidney j 15.4 JMelanoma SK-MEL-28 0.6

Kidney (fetal) j 12.1 j

Table PE. Panel 1.3D

Column A - Rel. Exp.(%) Agl48, Run 150018164 Column B - Rel. Exp.(%) Ag201, Run 152827283

Tissue Name B Tissue Name B

Liver adenocarcinoma 3.7 3.1 Kidney (fetal) 4.6 6.4

Pancreas 2.4 4.6 Renal ca. 786-0 1.5 0.8

Pancreatic ca. CAP AN 2 4.7 1.7 Renal ca. A498 7.3 8.2

Adrenal gland 4.8 4.5 Renal ca. RXF 393 0.4 0.0

Thyroid 20.6 23.8 Renal ca. ACHN 0.9 1.2

Salivary gland 1.0 2.8 Renal ca. UO-31 2.0 1.1

Pituitary gland 4.5 2.0 Renal ca. TK-10 3.3 6.7

Brain (fetal) 8.4 11.3 Liver 0.9 0.0

Brain (whole) 28.5 40.1 Liver (fetal) 0.7 2.1

Brain (amygdala) 48.3 1 50.0 Liver ca. (hepatoblast) HepG2 4.0 2.2

Brain (cerebellum) 7.5 7.3 Lung 0.6 1.3

Brain (hippocampus) 97.9 94.6 Lung (fetal) 0.7 2.4

Brain (substantia nigra) 5.8 8.0 Lung ca. (small cell) LX-1 4.5 4.5

Brain (thalamus) 30.4 28.1 Lung ca. (small cell) NCI-H69 19.1 18.8

Cerebral Cortex 33.4 36.9 Lung ca. (s.cell var.) SHP-77 3.0 4.1

Spinal cord 6.4 10.2 Lung ca. (large cell)NCI-H460 3.6 4.9 glio/astro U87-MG 0.9 1.7 Lung ca. (non-sm. cell) A549 1.7 3.2 glio/astro U-118-MG 1.5 3.2 Lung ca. (non-s.cell) NCI-H23 6.7 8.0 astrocytoma SW1783 1.0 1.4 Lung ca. (non-s.cell) HOP-62 5.4 1.8 neuro*; met SK-N-AS 4.9 6.0 Lung ca. (non-s.cl) NCI-H522 4.8 4.8 astrocytoma SF-539 3.4 2.0 Lung ca. (squam.) SW 900 1.0 1.2 astrocytoma SNB-75 5.8 10.6 Lung ca. (squam.) NCI-H596 4.6 3.4 glioma SNB-19 3.4 4.0 Mammary gland 2.2 3.1 glioma U251 3.3 3.6 Breast ca.* (pl.ef) MCF-7 3.1 3.3 glioma SF-295 9.3 10.7 Breast ca.* (pl.ef) MDA-MB-231 1.8 2.4

Heart (fetal) 2.5 1.7 Breast ca.* (pl.ef) T47D 1.6 5.2

Heart 0.8 0.4 Breast ca. BT-549 1.7 1.2

Skeletal muscle (fetal) 100.0 100.0 Breast ca. MDA-N 4.4 7.5

Skeletal muscle 0.3 0.3 Ovary 2.8 2.0

Table PF. Panel 2D

Table PG. Panel 4D

CNS_neurodegeneration_vl.0 Summary: Agl48/Ag201 This gene was down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, up-regulation of this gene, expressed protein, and/or treatment with specific agonists targeting encoded protein is useful in reversing the dementia/memory loss associated with this disease and neuronal death.

Panel 1 Summary: Agl48 Highest expression of this gene was detected in cerebellum (CT=24.5) and this gene was expressed at high levels in all regions of the central nervous system examined including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in the diagnosis and treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Moderate gene expression levels was also seen in pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, melanoma and brain cancer cell lines. Thus, expression level of this gene is a useful marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene is an effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, melanoma and brain cancers. Among tissues with metabolic or endocrine function, this gene was expressed at moderate to low levels in pancreas, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

Panel 1.3D Summary: Agl48/Ag201 Highest expression of this gene was seen in fetal skeletal muscle (CTs=30). Expression of this gene was higher in fetal compared adult skeletal muscle (CTs=38). The relative overexpression of this gene in fetal skeletal muscle indicates that the protein product enhances muscular growth or development and has regenerative capacity in the adult. Therefore, therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in treatment of muscle related diseases. More specifically, treatment of weak or dystrophic muscle with the protein encoded by this gene restores muscle mass or function. Moderate expression of this gene was seen in all the regions of the brain examined including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Modulation of this gene, the expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

Panel 2D Summary: Agl48/Ag201 Highest expression of this gene was seen in breast cancer and normal kidney samples (CTs=30-31). Moderate to low expression of this gene was also seen in normal and cancer samples from stomach, ovary, liver, breast, kidney, metastatic melanoma, lung, prostate and colon. Expression of this gene is consistently higher in normal kidney compared to the corresponding cancer samples. This gene codes for fibronectin leucine repeat transmembrane protein 1 (FLRT1) acts as a matrix adhesion molecule or cell-cell adhesion molecule. This gene or encoded FLRT1 protein inhibits the growth of kidney cancer cells.

Panel 4D Summary: Agl48/Ag201 Highest expression of this gene was detected in IL13 activated NCI-NCI-H292 cells and thymus (CTs=31). This gene showed low wide spread expression in this panel with higher expression in resting and activated mucoepidermoid NCI-NCI-H292 cells, activated dermal fibroblasts, resting and activated basophils, eosinophils, PBMC cells, activated B lymphocytes and normal colon. Therefore, modulation of the gene and/or encoded protein alters functions associated with these cell types and leads to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis. Q. CG96778-01: Human medium-chain acyl-CoA dehydrogenase.

Expression of gene CG96778-01 was assessed using the primer-probe set Ag4326, described in Table QA. Results of the RTQ-PCR runs are shown in Table QB.

Table OA. Probe Name Ag4326

Table QB. General_screening_panel_ l.4

General_screeningjpanel_vl.4 Summary: Ag4326 Highest expression of this gene was mainly seen in NCI-N87 gastric cancer cell line (CT=34.1). Low expression of this gene was also seen in brain and breast cancer cell lines. Therefore, expression level of this gene is a usedful marker to detect the presence of gastric, brain and breast cancers. In addition, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of these cancers.

R. CG96778-02: Medium-chain acyl-CoA dehydrogenase.

Expression of gene CG96778-02 was assessed using the primer-probe set Ag6978, described in Table RA. Results of the RTQ-PCR runs are shown in Table RB. This sequence represents a physical full length clone.

Table RA. Probe Name Ag6978

SEQ ID

Primers Sequences JLengthj Start Position No

Forward 5 ' -acttggtttaatgaacacacacatt-3 ' 25 249 448

TET-5 ' -ccagagaactgtgactacagtgtttgccc-3 '

Probe TAMRA 29 274 449 (Reverse j5 ' -gtatagagtgcaagcttccaaaagt-3 ' 25 303 450

Table RB. General_screening_panel_vl.6

General_screening_panel_vl.6 Summary: Ag6978 Highest expression of this gene was seen in cerebellum (CT=29.6). Moderate to low expression of this gene was seen in all the regions of central nervous system examined including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Low expression of this gene was also seen in fetal and adult heart. Therefore, modulation of this gene and/or encoded protein will be useful in the treatment of heart related diseases.

Example D: Expression Data

Example Dl: Expression of CG50949-07 in stable CHO-K1 cells

A 2548 bp long BamHI-XhoI fragment containing the CG52643-05 sequence was subcloned into BamHI-XhoI digested pEE14.4/Sec to generate plasmid 2134. The resulting plasmid 2134 was transfected into CHO-K1 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Invitrogen/Gibco Stable clones were selected based on resistance against methionine sulfoximine. The expression and secretion levels of the selected clones were assessed by Western blot analysis using HRP conjugated V5 antibody. (The V5 epitope is fused to the gene of interest at the Cter, in the pEE14.4Sec vector.) The CG50949-07 protein is secreted as a 55 kDa protein.

Example D2: Expression of CGS2643-05 using Baculovirus expression system.

A 2.5 kb BamHI-EcoRI fragment containing the CG52643-05 sequence was subcloned into BamHI-EcoRI digested pBlueBac4.5/V5-His (CuraGen Corporation) insect expression vector to generate plasmid 2599. Following standard procedures (Invitrogen pBlueBac protocol), recombinant baculovirus was generated and plaque-purified. Fresh Sf9 cells in adherent culture were infected with the recombinant baculovirus. The culture media were harvested 5 days post-infection and assayed for CG52643-05 protein expression by Western blot under reducing conditions using an anti-V5 antibody. CG52643-05 is expressed as 111 kDa protein.

Example D3: Expression of CG51051-06 in human embryonic kidney 293 cells.

A 1.29 kb BamHI-XhoI fragment containing the CG51051-06 sequence was subcloned into BamHI-XhoI digested pCEP4/Sec vector to generate plasmid 209. The resulting plasmid 209 was transfected into 293 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Gibco/BRL). The cell pellet and supernatant were harvested 72h post transfection and examined for CG51051-06 expression by Western blot (reducing conditions) using an anti-V5 antibody. CG51051-06 is expressed as a 60 kDa protein secreted by 293 cells.

Example D4: Epithelial Cell survival assay PE51al)

Netrins are a family of guidance molecules that act to both attract and repel the growing axons of a broad range of neuronal cell types during development and are also involved in controling neuronal cell migration. Netrin signaling occurs through specific receptor complexes containing either the colorectal cancer (DCC) or neogenin protein (attractive receptor), or the UNC-5-related proteins (repellent receptor). Netrin-DCC signaling has also been shown to regulate cell death in epithelial cells in vitro, raising the interesting possibility that netrins may also regulate cell death in the developing nervous system (Livesey et al., Cell. Mol. Life Sci. 1999 Oct l;56(l-2):62-8). CG51051-06 is related to the netrin family of neuronal guidance molecules related to neuronal spreading, migration, development and survival. CG51051-06 may act as a chemotrophic/survival potentiating factor in neuronal repair or regeneration.

BrdU Incorporation. Proliferative activity is measured by treatment of serum-starved cultured cells with a given agent and measurement of BRDU incorporation during DNA synthesis. 789-0 and 769-P kidney epithelial cells were cultured in DMEM supplemented with 10% fetal bovine serum or 10% calf serum respectively. Cells were grown to confluence at 37°C in 10% CO₂/air. Cells were then starved in DMEM for 24- 72 h. pCEP4sec or pCEP4sec/CG51051-06 enriched conditioned medium was added (10 μL/100 μL of culture ) for 18 h. BrdU (10 μM final concentration) was then added and incubated with the cells for 5 h. BrdU incorporation was assayed according to the manufacturer's specifications (Boehringer Mannheim, Indianapolis, IN).

CG51051-06 has shown BrdU incorporation activity on 786-0 and 769-P kidney epithelial cells. As shown in Figure 1, CG51051-06 promotes growth and survival of epithelial cells demonstrating that the molecule is functional and may act as a chemotrophic/survival potentiating factor in neuronal repair or regeneration.

Example D5: Expression of CG51051-07 in human embryonic kidney 293 cells.

A 1.5 kb fragment containing the CG51051-07 sequence was subcloned into pCEP4- Sec-GATEWAY vector to generate plasmid 1729. The resulting plasmid 1729 was transfected into 293 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Gibco/BRL). The cell pellet and supernatant were harvested 72h post transfection and examined for CG51051-07 expression by Western blot (reducing conditions) using an anti-V5 antibody. CG51051-07 is expressed as a 67 kDa protein secreted by 293 cells.

Example D6: Expression of CG52643-05 in stable CHO-K1 cells

A 2548 bp long BamHI-EcoRI fragment containing the CG52643-05 sequence was subcloned into BamHI-EcoRI digested pEE14.4FL2_MSA to generate plasmid 2809. The resulting plasmid 2809 was transfected into CHO-K1 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Invitrogen/Gibco Stable clones were selected based on resistance against methionine sulfoximine. The expression and secretion levels of the selected clones were assessed by Western blot analysis using HRP conjugated V5 antibody. (The V5 epitope is fused to the gene of interest at the Cter, in the pEE14.4Sec vector.) The CG52643-05 protein is secreted as a 178.4 kDa protein.

Example D7: Expression of CG52643-05 using Baculovirus expression system.

A 2.5 kb BamHI-EcoRI fragment containing the CG52643-05 sequence was subcloned into BamHI-EcoRI digested pBlueBac4.5/V5-His (CuraGen Corporation) insect expression vector to generate plasmid 2599. Following standard procedures (Invitrogen pBlueBac protocol), recombinant baculovirus was generated and plaque-purified. Fresh Sf9 cells in adherent culture were infected with the recombinant baculovirus. The culture media were harvested 5 days post-infection and assayed for CG52643-05 protein expression by Western blot under reducing conditions using an anti-N5 antibody. CG52643-05 is expressed as 111 kDa protein.

OTHER EMBODIMENTS

Although particular embodiments are disclosed herein in detail, this is done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications will be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims. The claims presented are representative of the inventions disclosed herein. Other, unclaimed inventions are also contemplated. Applicants reserve the right to pursue such inventions in later claims.

Claims

What is claimed is:

1. An isolated polypeptide comprising the mature form of an amino acid sequenced selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174.

2. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174.

3. An isolated polypeptide comprising an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174.

4. An isolated polypeptide, wherein the polypeptide comprises an amino acid sequence comprising one or more conservative substitutions in the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174.

5. The polypeptide of claim 1 wherein said polypeptide is naturally occurring.

6. A composition comprising the polypeptide of claim 1 and a carrier.

7. A kit comprising, in one or more containers, the composition of claim 6.

8. The use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease selected from a pathology associated with the polypeptide of claim 1, wherein the therapeutic comprises the polypeptide of claim 1.

9. A method for determining the presence or amount of the polypeptide of claim 1 in a sample, the method comprising:

(a) providing said sample; (b) introducing said sample to an antibody that binds immunospecifically to the polypeptide; and

(c) determining the presence or amount of antibody bound to said polypeptide, thereby determining the presence or amount of polypeptide in said sample.

10. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the polypeptide of claim 1 in a first mammalian subject, the method comprising: a) measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and b) comparing the expression of said polypeptide in the sample of step (a) to the expression of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, said disease, wherein an alteration in the level of expression of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to said disease.

11. A method of identifying an agent that binds to the polypeptide of claim 1 , the method comprising:

(a) introducing said polypeptide to said agent; and

(b) determining whether said agent binds to said polypeptide.

12. The method of claim 11 wherein the agent is a cellular receptor or a downstream effector.

13. A method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of the polypeptide of claim 1, the method comprising:

(a) providing a cell expressing the polypeptide of claim 1 and having a property or function ascribable to the polypeptide;

(b) contacting the cell with a composition comprising a candidate substance; and

(c) determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition in the absence of the substance, the substance is identified as a potential therapeutic agent.

14. A method for screening for a modulator of activity of or of latency or predisposition to a pathology associated with the polypeptide of claim 1, said method comprising:

(a) administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of claim 1, wherein said test animal recombinantly expresses the polypeptide of claim 1;

(b) measuring the activity of said polypeptide in said test animal after administering the compound of step (a); and

(c) comparing the activity of said polypeptide in said test animal with the activity of said polypeptide in a control animal not administered said polypeptide, wherein a change in the activity of said polypeptide in said test animal relative to said control animal indicates the test compound is a modulator activity of or latency or predisposition to, a pathology associated with the polypeptide of claim 1.

15. The method of claim 14, wherein said test animal is a recombinant test animal that expresses a test protein transgene or expresses said transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein said promoter is not the native gene promoter of said transgene.

16. A method for modulating the activity of the polypeptide of claim 1 , the method comprising contacting a cell sample expressing the polypeptide of claim 1 with a compound that binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.

17. A method of treating or preventing a pathology associated with the polypeptide of claim 1, the method comprising administering the polypeptide of claim 1 to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject.

18. The method of claim 17, wherein the subject is a human.

19. A method of treating a pathological state in a mammal, the method comprising administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 or a biologically active fragment thereof.

20. An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174.

21. The nucleic acid molecule of claim 20, wherein the nucleic acid molecule is naturally occurring.

22. A nucleic acid molecule, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 174.

23. An isolated nucleic acid molecule encoding the mature form of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174.

24. An isolated nucleic acid molecule comprising a nucleic acid selected from the group consisting of 2n-l, wherein n is an integer between 1 and 174.

25. The nucleic acid molecule of claim 20, wherein said nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-l, wherein n is an integer between 1 and 174, or a complement of said nucleotide sequence.

26. A vector comprising the nucleic acid molecule of claim 20.

27. The vector of claim 26, further comprising a promoter operably linked to said nucleic acid molecule.

28. A cell comprising the vector of claim 26.

29. An antibody that immunospecifically binds to the polypeptide of claim 1.

30. The antibody of claim 29, wherein the antibody is a monoclonal antibody.

31. The antibody of claim 29, wherein the antibody is a humanized antibody.

32. A method for determining the presence or amount of the nucleic acid molecule of claim 20 in a sample, the method comprising:

(a) providing said sample;

(b) introducing said sample to a probe that binds to said nucleic acid molecule; and

(c) determining the presence or amount of said probe bound to said nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in said sample.

33. The method of claim 32 wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.

34. The method of claim 33 wherein the cell or tissue type is cancerous.

35. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the nucleic acid molecule of claim 20 in a first mammalian subject, the method comprising: a) measuring the level of expression of the nucleic acid in a sample from the first mammalian subject; and b) comparing the level of expression of said nucleic acid in the sample of step (a) to the level of expression of the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of expression of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

36. A method of producing the polypeptide of claim 1 , the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174.

37. The method of claim 36 wherein the cell is a bacterial cell.

38. The method of claim 36 wherein the cell is an insect cell.

39. The method of claim 36 wherein the cell is a yeast cell.

40. The method of claim 36 wherein the cell is a mammalian cell.

41. A method of producing the polypeptide of claim 2, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-l, wherein n is an integer between 1 and 174.

42. The method of claim 41 wherein the cell is a bacterial cell.

43. The method of claim 41 wherein the cell is an insect cell.

44. The method of claim 41 wherein the cell is a yeast cell.

45. The method of claim 41 wherein the cell is a mammalian cell.