WO2001012660A2 - Proteines humaines a domaines hydrophobes et adn codant pour ces proteines - Google Patents

Proteines humaines a domaines hydrophobes et adn codant pour ces proteines Download PDF

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Publication number
WO2001012660A2
WO2001012660A2 PCT/JP2000/005356 JP0005356W WO0112660A2 WO 2001012660 A2 WO2001012660 A2 WO 2001012660A2 JP 0005356 W JP0005356 W JP 0005356W WO 0112660 A2 WO0112660 A2 WO 0112660A2
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protein
present
amino acid
sequences
proteins
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PCT/JP2000/005356
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WO2001012660A3 (fr
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Seishi Kato
Tomoko Kimura
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Sagami Chemical Research Center
Protegene Inc.
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Priority to EP00950056A priority Critical patent/EP1206536A2/fr
Priority to AU63214/00A priority patent/AU6321400A/en
Publication of WO2001012660A2 publication Critical patent/WO2001012660A2/fr
Publication of WO2001012660A3 publication Critical patent/WO2001012660A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals

Definitions

  • membrane proteins play important roles, as signal receptors, ion channels, transporters and the like in the material transport and the signal transduction through the cell membrane.
  • Examples thereof include receptors for various cytokines , ion channels for the sodium ion, the potassium ion, the chloride ion and the like, transporters for saccharides and amino acids and the like.
  • the genes for many of them have already been cloned. It has been clarified that abnormalities in these membrane proteins are involved in a number of previously cryptogenic diseases. Therefore, discovery of a new membrane protein is expected to lead to elucidation of the causes of many diseases, so that isolation of new genes encoding the membrane proteins has been desired.
  • a general method is the so-called expression cloning method, in which a cDNA library is introduced into eukaryotic cells to express cDNAs , and the cells secreting, or expressing on the surface of membrane, the protein having the activity of interest are then screened.
  • a cDNA library is introduced into eukaryotic cells to express cDNAs , and the cells secreting, or expressing on the surface of membrane, the protein having the activity of interest are then screened.
  • genes for proteins with known functions can be cloned by using this method.
  • a secretory protein or a membrane protein possesses at least one hydrophobic domain within the protein. After synthesis on ribosomes, such domain works as a secretory signal or remains in the phospholipid membrane to be entrapped in the membrane. Accordingly, if the existence of a highly hydrophobic domain is observed in the amino acid sequence of a protein encoded by a cDNA when the whole base sequence of the full-length cDNA is determined, it is considered that the cDNA encodes a secretory protein or a membrane protein.
  • the main object of the present invention is to provide novel human proteins having hydrophobic domains , DNAs encoding these proteins, expression vectors for these DNAs, transformed eukaryotic cells that are capable of expressing these DNAs and antibodies directed to these proteins.
  • the present invention provides a human protein having hydrophobic domain (s), namely a protein comprising any one of an amino acid sequence selected from the group consisting of SEQ ID NOS: 1 to 10, 31 to 40, 61 to 70, 91 to 100 and 121 to 130.
  • Fig. 5 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03499.
  • Fig. 6 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03500.
  • Fig. 8 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10703.
  • Fig. 9 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10711.
  • Fig. ' 10 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10712.
  • Fig. 11 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03010.
  • Fig. 12 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03576.
  • Fig. 13 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03611.
  • Fig. 14 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03612.
  • Fig. 15 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10407.
  • Fig. 17 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10714.
  • Fig. 18 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10716.
  • Fig. 19 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10717.
  • Fig. 20 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10718.
  • Fig. 21 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03745.
  • Fig. 22 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03747.
  • Fig. 23 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10719.
  • Fig. 24 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10720.
  • Fig. 25 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10721.
  • Fig. 26 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10725.
  • Fig. 27 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10727.
  • Fig. 32 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03831.
  • Fig. 35 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10704.
  • Fig. 38 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10733.
  • Fig. 39 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10734.
  • Fig. 40 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10756.
  • Fig. 41 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP03670.
  • Fig. 45 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10765.
  • Fig. 47 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10770.
  • Fig. 50 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10776.
  • the proteins of the present invention can be obtained, for example, by a method for isolating proteins from human organs, cell lines or the like, a method for preparing peptides by the chemical synthesis based on the amino acid sequences of the present invention, or a method for producing proteins by the recombinant DNA technology using the DNAs encoding the hydrophobic domains of the present invention.
  • the method for producing proteins by the recombinant DNA technology is preferably employed.
  • the proteins can be expressed in vitro by preparing an RNA by in vitro transcription from a vector having the cDNA of the present invention, and then carrying out in vitro translation using this RNA as a template.
  • the protein of the present invention can be produced in vitro by incorporating the translated region of this cDNA into a vector having an RNA polymerase promoter, and then adding the vector to an in vitro translation system such as a rabbit reticulocyte lysate or a wheat germ extract, which contains an RNA polymerase corresponding to the promoter.
  • an in vitro translation system such as a rabbit reticulocyte lysate or a wheat germ extract, which contains an RNA polymerase corresponding to the promoter.
  • the RNA polymerase promoters are exemplified by T7 , T3, SP6 and the like.
  • the vectors containing promoters for these RNA polymerases are exemplified by pKAl , pCDM8 , pT3/T7 18, pT7/3 19, pBluescript II and the like.
  • the protein of the present invention can be expressed in the secreted form or the form incorporated in the microsome membrane when a canine pancreas microsome or the like is added to the reaction system.
  • the protein of the present invention is produced by expressing the DNA in a microorganism such as Escherichia coli etc.
  • a recombinant expression vector in which the translated region of the cDNA of the present invention is incorporated into an expression vector having an origin which is capable of replicating in the microorganism, a promoter, a ribosome-binding site, a cDNA-cloning site, a terminator and the like is constructed. After transformation of the host cells with this expression vector, the resulting transformant is cultivated, whereby the protein encoded by the cDNA can be produced in large quantities in the microorganism.
  • a protein fragment containing any translated region can be obtained by adding an initiation codon and a termination codon in front of and behind the selected translated region to express the protein.
  • the protein can be expressed as a fusion protein with another protein. Only the portion of the protein encoded by the cDNA can be obtained by cleaving this fusion protein with a suitable protease.
  • the expression vectors for Escherichia coli are exemplified by the pUC series, pBluescript II, the pET expression system, the pGEX expression system and the like.
  • the protein of the present invention is produced by expressing the DNA in eukaryotic cells
  • the protein of the present invention can be produced as a secretory protein, or as a membrane protein on the surface of cell membrane, by incorporating the translated region of the cDNA into an expression vector for eukaryotic cells that has a promoter, a splicing region, a poly (A) addition site and the like, and then introducing the vector into the eukaryotic cells.
  • the expression vectors are exemplified by pKAl , pED6dpc2 , pCDM8 , pSVK3 , pMSG, pSVL, pBK-CMV, pBK-RSV, EBV vectors, pRS , pYES2 and the like.
  • eukaryotic cells to be used in general include mammalian cultured cells such as monkey kidney COS7 cells, Chinese hamster ovary CHO cells and the like, budding yeasts, fission yeasts, silkworm cells, Xenopus oocytes and the like. Any eukaryotic cells may be used as long as they are capable of expressing the proteins of the present invention.
  • the expression vector can be introduced into the eukaryotic cells by using a method known in the art such as the electroporation method, the calcium phosphate method, the liposome method, the DEAE-dextran method and the like.
  • membrane proteins undergo the processing on the cell surface to be converted to the secreted forms .
  • Such proteins or peptides in the secreted forms shall also come within the scope of the protein of the present invention.
  • expression of the proteins in appropriate eukaryotic cells affords the proteins to which sugar chains are added. Accordingly, such proteins or peptides to which sugar chains are added shall also come within the scope of the protein of the present invention.
  • the DNAs of the present invention include all the DNAs encoding the above-mentioned proteins . These DNAs can be obtained by using a method for chemical synthesis, a method for cDNA cloning and the like.
  • the cDNAs of the present invention can be cloned, for example, from cDNA libraries derived from the human cells.
  • the cDNAs are synthesized by using poly (A) + RNAs extracted from human cells as templates.
  • the human cells may be cells delivered from the human body, for example, by the operation or may be the cultured cells.
  • the cDNAs can be synthesized by using any method such as the Okayama-Berg method [Okayama, H. and Berg, P., Mol. Cell. Biol. 2: 161- 170 (1982)], the Gubler-Hoffman method [Gubler, U. and Hoffman, J. , Gene 25: 263-269 (1983)] and the like.
  • cDNAs of the present invention can be cloned from the cDNA libraries by synthesizing an oligonucleotide on the basis of base sequences of any portion in the cDNA of the present invention and screening the cDNA libraries using this oligonucleotide as a probe for colony or plaque hybridization according to a method known in the art.
  • the cDNAs of the present invention are characterized in that they comprise any one of the base sequences represented by SEQ ID NOS: 11 to 20, 41 to 50, 71 to 80, 101 to 110 and 131 to 140 or the base sequences represented by SEQ ID NOS: 21 to 30, 51 to 60, 81 to 90, 111 to 120 and 141 to 150.
  • Tables 1 and 2 summarizes the clone number (HP number) , the cell from which the cDNA clone was obtained, the total number of bases of the cDNA, and the number of the amino acid residues of the encoded protein, for each of the cDNAs .
  • any protein in which one or plural amino acids are added, deleted and/or substituted with other amino acids resulting from the above-mentioned changes shall come within the scope of the present invention, as long as the protein possesses the activity of the protein having any one of the amino acid sequences represented by SEQ ID NOS: 1 to 10, 31 to 40, 61 to 70, 91 to 100 and 121 to 130.
  • the cDNAs of the present invention also include cDNA fragments (of 10 bp or more) containing any partial base sequence in the base sequences represented by SEQ ID NOS: 11 to 20, 41 to 50, 71 to 80, 101 to 110 and 131 to 140 or in the base sequences represented by SEQ ID NOS: 21 to 30, 51 to 60, 81 to 90, 111 to 120 and 141 to 150. Also, DNA fragments consisting of a sense strand and an anti-sense strand shall come within this scope. These DNA fragments can be utilized as the probes for the genetic diagnosis.
  • the antibody of the present invention can be obtained from a serum after immunizing an animal using the protein of the present invention as an antigen.
  • a peptide that is chemically synthesized based on the amino acid sequence of the present invention and a protein expressed in eukaryotic or prokaryotic cells can be used as an antigen.
  • an antibody can be prepared by introducing the above-mentioned expression vector for eukaryotic cells into the muscle or the skin of an animal by injection or by using a gene gun and then collecting a serum therefrom (JP-A 7-313187) .
  • Animals that can be used include a mouse, a rat, a rabbit, a goat, a chicken and the like.
  • a monoclonal antibody directed to the protein of the present invention can be produced by fusing B cells collected from the spleen of the immunized animal with myelomas to generate hybridomas .
  • the polynucleotides provided by the present invention can be used by the research community for various purposes.
  • the polynucleotides can be used to express recombinant protein for analysis, characterization or therapeutic use; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in disease states) ; as molecular weight markers on Southern gels ; as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions; to compare with endogenous DNA sequences in patients to identify potential genetic disorders; as probes to hybridize and thus discover novel, related DNA sequences; as a source of information to derive PCR primers for genetic fingerprinting; as a probe to "subtract-out" known sequences in the process of discovering other novel polynucleotides; for selecting and making oligomers for attachment to a "gene chip” or other support, including for examination of expression patterns; to raise anti-protein antibodies using DNA immun
  • the protein binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction)
  • the protein can be used to identify the other protein with which binding occurs or to identify inhibitors of the binding interaction. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction. Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products.
  • Polynucleotides and proteins of the present invention can also be used as nutritional sources or supplements. Such uses include without limitation use as a protein or amino acid supplement, use as a carbon source, use as a nitrogen source and use as a source of carbohydrate.
  • the protein or polynucleotide of the invention can be added to the feed of a particular organism or can be administered as a separate solid or liquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules.
  • the protein or polynucleotide of the invention can be added to the medium in or on which the microorganism is cultured. Cytokine and Cell Proliferation/Differentiation Activity
  • a protein of the present invention may exhibit cytokine, cell proliferation (either inducing or inhibiting) or cell differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations.
  • cytokine cytokine
  • cell proliferation either inducing or inhibiting
  • cell differentiation either inducing or inhibiting
  • the activity of a protein of the present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for cell lines including, without limitation, 32D, DA2 , DA1G, T10, B9 , B9/11, BaF3, MC9/G, M+ (preB M+) , 2E8, RB5 , DAI, 123, T1165, HT2, CTLL2, TF-1, Mo7e and CMK.
  • the activity of a protein of the invention may, among other means, be measured by the following methods:
  • Assays for T-cell or thymocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986; Bertagnolli et al . , J. Immunol. 145:1706-1712, 1990; Bertagnolli et al .
  • Assays for cytokine production and/or proliferation of spleen cells, lymph node cells or thymocytes include, without limitation, those described in: Polyclonal T cell stimulation, Kruisbeek, A.M. and Shevach, E.M. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto.
  • APC-T cell interactions as well as direct T-cell effects by measuring proliferation and cytokine production include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans); Weinberger et al . , Proc. Natl. Acad. Sci. USA 77:6091-6095, 1980; Weinberger et al . , Eur. J. Immun.
  • a protein of the present invention may also exhibit immune stimulating or immune suppressing activity, including without limitation the activities for which assays are described herein.
  • a protein may be useful in the treatment of various immune deficiencies and disorders (including severe combined immunodeficiency (SCID) ) , e.g., in regulating (up or down) growth and proliferation of T and/or B lymphocytes, as well as effecting the cytolytic activity of NK cells and other cell populations.
  • SCID severe combined immunodeficiency
  • Assays for proteins that influence early steps of T-cell commitment and development include, without limitation, those described in: Antica et al . , Blood 84:111- 117, 1994; Fine et al . , Cellular Immunology 155:111-122, 1994; Galy et al . , Blood 85:2770-2778, 1995; Toki et al . , Proc. Nat. Acad Sci. USA 88:7548-7551, 1991.
  • Hematopoiesis Regulating Activity A protein of the present invention may be useful in regulation of hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell deficiencies.
  • a protein of the present invention which induces tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normally formed, has application in the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals.
  • Such a preparation employing a tendon/ligament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue.
  • Assays for tissue generation activity include, without limitation, those described in: International Patent
  • Assays for activin/inhibin activity include, without limitation, those described in: Vale et al . , Endocrinology 91:562-572, 1972; Ling et al . , Nature 321:779- 782, 1986; Vale et al . , Nature 321:776-779, 1986; Mason et al., Nature 318:659-663, 1985; Forage et al., Proc. Natl. Acad. Sci. USA 83:3091-3095, 1986.
  • a protein of the present invention may have chemotactic or chemokinetic activity (e.g., act as a chemokine) for mammalian cells, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells.
  • Chemotactic and chemokinetic proteins can be used to mobilize or attract a desired cell population to a desired site of action.
  • Chemotactic or chemokinetic proteins provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of localized infections. For example, attraction of lymphocytes, monocytes or neutrophils to tumors or sites of infection may result in improved immune responses against the tumor or infecting agent.
  • a protein or peptide has chemotactic activity for a particular cell population if it can stimulate, directly or indirectly, the directed orientation or movement of such cell population.
  • the protein or peptide has the ability to directly stimulate directed movement of cells. Whether a particular protein has chemotactic activity for a population of cells can be readily determined by employing such protein or peptide in any known assay for cell chemotaxis .
  • the activity of a protein of the invention may, among other means , be measured by the following methods :
  • Assays for chemotactic activity consist of assays that measure the ability of a protein to induce the migration of cells across a membrane as well as the ability of a protein to induce the adhesion of one cell population to another cell population.
  • Suitable assays for movement and adhesion include, without limitation, those described in: Current Protocols in Immunology, Ed by J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley- Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 6.12.1-6.12.28; Taub et al.' J. Clin. Invest.
  • Assay for hemostatic and thrombolytic activity include, without limitation, those described in: Linet et al., J. Clin. Pharmacol. 26:131-140, 1986; Burdick et al . , Thrombosis Res. 45:413-419, 1987; Humphrey et al . , Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467- 474, 1988.
  • the activity of a protein of the invention may, among other means, be measured by the following methods:
  • Proteins exhibiting such activities can be used to treat inflammatory conditions including chronic or acute conditions) , including without limitation inflammation associated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS) ) , ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting from over production of cytokines such as TNF or IL-1. Proteins of the invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or material.
  • a protein of the invention may exhibit other anti-tumor activities .
  • a protein may inhibit tumor growth directly or indirectly (such as, for example, via ADCC) .
  • a protein may exhibit its tumor inhibitory activity by acting on tumor tissue or tumor precursor tissue, by inhibiting formation of tissues necessary to support tumor growth (such as, for example, by inhibiting angiogenesis) , by causing production of other factors, agents or cell types which inhibit tumor growth, or by suppressing, eliminating or inhibiting factors, agents or cell types which promote tumor growth.
  • the present invention is specifically illustrated in more detail by the following Examples, but Examples are not intended to restrict the present invention.
  • the basic procedures with regard to the recombinant DNA and the enzymatic reactions were carried out according to the literature ["Molecular Cloning. A Laboratory Manual", Cold Spring Harbor Laboratory, 1989] . Unless otherwise stated, restriction enzymes and various modifying enzymes to be used were those available from Takara Shuzo.
  • the buffer compositions and the reaction conditions for each of the enzyme reactions were as described in the attached instructions.
  • the cDNA synthesis was carried out according to the literature [Kato, S. et al . , Gene 150: 243-250 (1994) ] .
  • Full-length cDNA clones were selected from the respective libraries and the whole base sequences thereof were determined to construct a homo-protein cDNA bank consisting of the full-length cDNA clones.
  • the hydrophobicity/hydrophilicity profiles were determined for the proteins encoded by the full-length cDNA clones registered in the homo-protein cDNA bank by the Kyte- Doolittle method [Kyte, J. & Doolittle, R. F., J. Mol. Biol. 157: 105-132 (1982)] to examine the presence or absence of a hydrophobic domain.
  • a clone that has a hydrophobic region being assumed as a secretory signal or a transmembrane domain in the amino acid sequence of the encoded protein was selected as a clone candidate.
  • the plasmid vector bearing the cDNA of the present invention was used for in vitro transcription/translation with a T N T rabbit reticulocyte lysate kit (Promega) .
  • T N T rabbit reticulocyte lysate kit Promega
  • [ 35 S]methionine was added to label the expression product with a radioisotope.
  • Each of the reactions was carried out according to the protocols attached to the kit.
  • Escherichia coli cells harboring the expression vector for the protein of the present invention were cultured at 37 °C for 2 hours in 2 ml of the 2 x YT culture medium containing 100 ⁇ g/ml of ampicillin, the helper phage M13K07 (50 ⁇ 1) was added thereto, and the cells were then cultured at 37 °C overnight.
  • Single-stranded phage particles were obtained by polyethylene glycol precipitation from a supernatant separated by centrifugation. The particles were suspended in 100 ⁇ l of 1 mM Tris-0.1 mM EDTA, pH 8 (TE) .
  • the cultured cells derived from monkey kidney, COS7 were cultured at 37 °C in the presence of 5% C0 2 in the Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal calf serum.
  • DMEM Dulbecco's modified Eagle's medium
  • 1 x 10 5 C0S7 cells were inoculated into a 6-well plate (Nunc, well diameter: 3 cm) and cultured at 37 °C for 22 hours in the presence of 5% C0 2 . After the medium was removed, the cell surface was washed with a phosphate buffer solution followed by DMEM containing 50 mM Tris- hydrochloride (pH 7.5) (TDMEM) .
  • a plasmid vector containing the cDNA of the present invention was dissolved in a phosphate buffer solution (PBS: 145 mM NaCI, 2.68 mM KC1 , 8.09 mM Na 2 HP0 4 , 2 mM KH 2 P0 4 , pH 7.2) to a concentration of 2 ⁇ g/ ⁇ l. 25 ⁇ l each
  • ⁇ HP03171> (SEQ ID NOS: 1, 11 and 21) Determination of the whole base sequence of the cDNA insert of clone HP03171 obtained from cDNA library of human thymus revealed the structure consisting of a 90-bp 5 '-untranslated region, a 804-bp ORF, and a 1148-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 267 amino acid residues and there existed one putative transmembrane domain.
  • Figure 1 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein.
  • the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively.
  • the both proteins shared a homology of 43.0% in the entire region.
  • the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AL036384) among ESTs . However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP03444> (SEQ ID NOS: 3, 13 and 23) Determination of the whole base sequence of the cDNA insert of clone HP03444 obtained from cDNA library of human kidney revealed the structure consisting of a 209-bp 5 '-untranslated region, a 1248-bp ORF, and a 460-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 415 amino acid residues and there existed a putative secretory signal at the N-terminus .
  • Figure 3 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. D78874) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP03478> (SEQ ID NOS: 4, 14 and 24) Determination of the whole base sequence of the cDNA insert of clone HP03478 obtained from cDNA library of human umbilical cord blood revealed the structure consisting of a 224-bp 5 '-untranslated region, a 1143-bp ORF, and a 891-bp 3 '-untranslated region.
  • the ORF encodes a protein consisting of 380 amino acid residues and there existed five putative transmembrane domains .
  • Figure 4 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
  • Table 6 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and Halocynthia roretzi HrPET-1 protein (HR) .
  • HP human protein of the present invention
  • HR Halocynthia roretzi HrPET-1 protein
  • the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively.
  • the both proteins shared a homology of 36.8% in the entire region.
  • the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example ,
  • Table 7 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and Chinese hamster hypothetical protein 2BE2121 (CH) .
  • HP human protein of the present invention
  • CH Chinese hamster hypothetical protein 2BE2121
  • the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively.
  • the both proteins shared a homology of 44.8% in the entire region.
  • FIG. 10 depicts the hydrophobicity/hydrophilicity profile , obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
  • the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. W22566) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP03611> (SEQ ID NOS: 33, 43 and 53) Determination of the whole base sequence of the cDNA insert of clone HP03611 obtained from cDNA library of human kidney revealed the structure consisting of a 189-bp 5 '-untranslated region, a 1464-bp ORF, and a 105-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 487 amino acid residues and there existed eleven putative transmembrane domains.
  • Figure 13 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight. The search of the protein database using the amino acid sequence of the present protein revealed that the protein was similar to human cystine/glutamate transporter
  • Table 13 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and human cystine/glutamate transporter (CG) .
  • HP human protein of the present invention
  • CG human cystine/glutamate transporter
  • the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example ,
  • Figure 14 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 39 kDa that was somewhat larger than the molecular weight of 37,930 predicted from the ORF.
  • Table 14 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and human monocarboxylate transporter
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AI742291) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10407> (SEQ ID NOS: 35, 45 and 55) Determination of the whole base sequence of the cDNA insert of clone HP10407 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 100-bp 5 '-untranslated region, a 1053-bp ORF, and a 332-bp 3 '-untranslated region.
  • the ORF encodes a protein consisting of 350 amino acid residues and there existed at least four putative transmembrane ⁇ domains.
  • Figure 15 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein.
  • ⁇ HP10713> (SEQ ID NOS: 36, 46 and 56) Determination of the whole base sequence of the cDNA insert of clone HP10713 obtained from cDNA library of human kidney revealed the structure consisting of a 79-bp 5 '-untranslated region, a 2004-bp ORF, and a 611-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 667 amino acid residues and there existed nine putative transmembrane domains.
  • Figure 16 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
  • the search of the protein database using the amino acid sequence of the present protein revealed that the protein was similar to mouse retinoic acid-responsive protein (Accession No. AAC16016) .
  • Table 15 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and mouse retinoic acid- responsive protein (MM) .
  • HP human protein of the present invention
  • MM mouse retinoic acid- responsive protein
  • the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively.
  • the both proteins shared a homology of 74.1% in the entire region.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AI760170) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10714> (SEQ ID NOS: 37, 47 and 57) Determination of the whole base sequence of the cDNA insert of clone HP10714 obtained from cDNA library of human umbilical cord blood revealed the structure consisting of a 82-bp 5 '-untranslated region, a 1395-bp ORF, and a 1820-bp 3 '-untranslated region.
  • the ORF encodes a protein consisting of 464 amino acid residues and there existed a putative secretory signal at the N-terminus.
  • Figure 17 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA861134) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10716> (SEQ ID NOS: 38, 48 and 58) Determination of the whole base sequence of the cDNA insert of clone HP10716 obtained from cDNA library - of human umbilical cord blood revealed the structure consisting of a 60-bp 5 '-untranslated region, a 1413-bp ORF, and a 653- bp 3 '-untranslated region.
  • the ORF encodes a protein consisting of 470 amino acid residues and there existed one putative transmembrane domain at the N-terminus.
  • Figure 18 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 61 kDa that was larger than the molecular weight of 52,086 predicted from the ORF.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example. Accession No. AI478174) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10718> (SEQ ID NOS: 40, 50 and 60) Determination of the whole base sequence of the cDNA insert of clone HP10718 obtained from cDNA library of human umbilical cord blood revealed the structure consisting of a 86-bp 5 '-untranslated region, a 813-bp ORF, and a 889- bp 3 '-untranslated region.
  • the ORF encodes a protein consisting of 270 amino acid residues and there existed three putative transmembrane domains.
  • Figure 20 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 28 kDa that was smaller than the molecular weight of 31,116 predicted from the ORF.
  • the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example. Accession No. AA176107) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • the region from position 466 to position 778 of the cDNA of the present invention matched with the region from position 2 to position 314 of human ubiquitin-conjugating enzyme E2 variant 1 (Accession NO. NM_003349) although no match was observed in another region.
  • ⁇ HP03745> (SEQ ID NOS: 61, 71 and 81) Determination of the whole base sequence of the cDNA insert of clone HP03745 obtained from cDNA library of human kidney revealed the structure consisting of a 99-bp 5 '-untranslated region, a 1170-bp ORF, and a 107-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 389 amino acid residues and there existed at least nine putative transmembrane domains.
  • Figure 21 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
  • Table 18 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and human solute carrier family 7
  • HP SVDNMKLP EMTAPL—PPLSGLALFLIVFFSLVFSVFAIVIGIILYNKWQEQSRK
  • the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA262924) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10719> (SEQ ID NOS: 63, 73 and 83) Determination of the whole base sequence of the cDNA insert of clone HP10719 obtained from cDNA library of human kidney revealed the structure consisting of a 54-bp 5 '-untranslated region, a 786-bp ORF, and a 576-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 261 amino acid residues and there existed a putative secretory signal at the N-terminus and one putative transmembrane domain in the inner portion.
  • Figure 23 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein.
  • Table 20 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and mouse endomucin (MM) .
  • HP human protein of the present invention
  • MM mouse endomucin
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example. Accession No. AA486620) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10720> (SEQ ID NOS: 64, 74 and 84) Determination of the whole base sequence of the cDNA insert of clone HP10720 obtained from cDNA library of human kidney revealed the structure consisting of a 25-bp 5 '-untranslated region, a 669-bp ORF, and a 653-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 222 amino acid residues and there existed a putative secretory signal at the N-terminus and one putative transmembrane domain in the inner portion.
  • Figure 24 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AI792241) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10721> SEQ ID NOS: 65, 75 and 85
  • ⁇ HP10725> (SEQ ID NOS: 66, 76 and 86) Determination of the whole base sequence of the cDNA insert of clone HP10725 obtained from cDNA library of human kidney revealed the structure consisting of a 235-bp 5 '-untranslated region, a 789-bp ORF, and a 713-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 262 amino acid residues and there existed one putative transmembrane domain.
  • Figure 26 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
  • GenBank using the base sequences of the present cDNA has- revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AI127782) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10727> SEQ ID NOS: 67, 77 and 87
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. R80316) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10728> (SEQ ID NOS: 68, 78 and 88) Determination of the whole base sequence of the cDNA insert of clone HP10728 obtained from cDNA library of human umbilical cord blood revealed the structure consisting of a 221-bp 5 '-untranslated region, a 732-bp ORF, and a 902- bp 3 '-untranslated region.
  • the ORF encodes a protein consisting of 243 amino acid residues and there existed one putative transmembrane domain at the N-terminus.
  • Figure 28 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 30 kDa that was larger than the molecular weight of 26,534 predicted from the ORF.
  • the ORF encodes a protein consisting of 428 amino acid residues and there existed one putative transmembrane domain.
  • Figure 29 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 50 kDa that was somewhat larger than the molecular weight of 48,992 predicted from the ORF.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. C19105) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. T35949) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP03800> (SEQ ID NOS: 91, 101 and 111) Determination of the whole base sequence of the cDNA insert of clone HP03800 obtained from cDNA library of human umbilical cord blood revealed the structure consisting of a 67-bp 5 '-untranslated region, a 1431-bp ORF, and a 135- bp 3 '-untranslated region.
  • the ORF encodes a protein consisting of 476 amino acid residues and there existed a putative secretory signal at the N-terminus.
  • Figure 31 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein.
  • Table 21 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and mosquito vitellogenic carboxypeptidase (VC) .
  • HP human protein of the present invention
  • VC mosquito vitellogenic carboxypeptidase
  • the both proteins shared a homology of 44.5% in the entire region.
  • the C-terminal portion beginning from alanine at position 182 matched with human probable carboxypeptidase (Accession No. AAC23787) except one amino acid residue.
  • ⁇ HP03831> (SEQ ID NOS: 92, 102 and 112) Determination of the whole base sequence of the cDNA insert of clone HP03831 obtained from cDNA library of human kidney revealed the structure consisting of a 191-bp 5 '-untranslated region, a 681-bp ORF, and a 223-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 226 amino acid residues and there existed four putative transmembrane domains.
  • Figure 32 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
  • the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example , Accession No . N41613) among ESTs .
  • they since they are partial sequences , it can not be j udged whether or not they encode the same protein as the protein of the present invention .
  • HP MRFTY . *.. CT RCFVF The search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example. Accession No. F06459) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention. ⁇ HP03880> (SEQ ID NOS: 94, 104 and 114)
  • Table 24 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and rat phosphatidylethanolamine-binding protein (RN) .
  • HP human protein of the present invention
  • RN rat phosphatidylethanolamine-binding protein
  • the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively.
  • the both proteins shared a homology of 37.6% in the region of 133 amino acid residues other than the N-terminal region.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. H83784) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10704> (SEQ ID NOS: 95, 105 and 115) Determination of the whole base sequence of the cDNA insert of clone HP10704 obtained from cDNA library of human kidney revealed the structure consisting of a 141-bp 5 '-untranslated region, a 1326-bp ORF, and a 399-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 441 amino acid residues and there existed eight putative transmembrane domains.
  • Figure 35 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
  • ⁇ HP10715> (SEQ ID NOS: 96, 106 and 116) Determination of the whole base sequence of the cDNA insert of clone HP10715 obtained from cDNA library of human umbilical cord blood revealed the structure consisting of a 49-bp 5 '-untranslated region, a 798-bp ORF, and a 1351- bp 3 '-untranslated region.
  • the ORF encodes a protein consisting of 265 amino acid residues and there existed two putative transmembrane domains.
  • Figure 36 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein.
  • ⁇ HP10733> (SEQ ID NOS: 98, 108 and 118) Determination of the whole base sequence of the cDNA insert of clone HP10733 obtained from cDNA library of human umbilical cord blood revealed the structure consisting of a 102-bp 5 '-untranslated region, a 1203-bp ORF, and a 222-bp 3 '-untranslated region.
  • the ORF encodes a protein consisting of 400 amino acid residues and there existed a putative secretory signal at the N-terminus and one putative transmembrane domain in the inner portion.
  • Figure 38 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example , Accession No . AI286184 ) among ESTs . However , since they are partial sequences , it can not be j udged whether or not they encode the same protein as the protein of the present invention .
  • Table 27 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and human sodium channel ⁇ 2 subunit (SC) .
  • HP human protein of the present invention
  • SC human sodium channel ⁇ 2 subunit
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. C03216) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10756> (SEQ ID NOS: 100, 110 and 120) Determination of the whole base sequence of the cDNA insert of clone HP10756 obtained from cDNA library of human kidney revealed the structure consisting of a 49-bp 5 '-untranslated region, a 783-bp ORF, and a 166-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 260 amino acid residues and there existed a putative secretory signal at the N-terminus.
  • Figure 40 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 27 kDa that was almost identical with the molecular weight of 27,356 predicted from the ORF.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AW027769) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • Mycobacterium tuberculosis hypothetical protein Rv0235c (MT) .
  • the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively.
  • the both proteins shared a homology of 41.7% in the entire region other than the N-terminal region.
  • the region from alanine at position 293 to proline at position 502 matched with human putative novel protein c360B4.1
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example. Accession No. AI792834) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AI792771) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • ⁇ HP10773> (SEQ ID NOS: 129, 139 and 149) Determination of the whole base sequence of the cDNA insert of clone HP10773 obtained from cDNA library of human kidney revealed the structure consisting of a 186-bp 5 '-untranslated region, a 489-bp ORF, and a 499-bp 3'- untranslated region.
  • the ORF encodes a protein consisting of 162 amino acid residues and there existed four putative transmembrane domains.
  • Figure 49 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte- Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
  • GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. N33828) among ESTs. However, since they are partial sequences, it can not be judged whether or not they encode the same protein as the protein of the present invention.
  • Cells into which these genes are introduced to express these proteins can be utilized for detection of the corresponding receptors or ligands, screening of novel small molecule pharmaceuticals and the like.
  • the antibody of the present invention can be utilized for the detection, quantification, purification and the like of the protein of the present invention.
  • the present invention also provides genes corresponding to the polynucleotide sequences disclosed herein. "Corresponding genes" are the regions of the genome that are transcribed to produce the mRNAs from which cDNA polynucleotide sequences are derived and may include contiguous regions of the genome necessary for the regulated expression of such genes.
  • Corresponding genes may therefore include but are not limited to coding sequences, 5' and 3' untranslated regions, alternatively spliced exons , introns , promoters, enhancers, and silencer or suppressor elements.
  • the corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and/or amplification of genes in appropriate genomic libraries or other sources of genomic materials.
  • An "isolated gene” is a gene that has been separated from the adjacent coding sequences, if any, present in the genome of the organism from which the gene was isolated.

Abstract

La présente invention concerne des protéines humaines comprenant des domaines hydrophobes, des ADN codant pour ces protéines, des vecteurs d'expression pour ces ADN, des cellules eucaryotes transformées capables d'exprimer ces ADN et des anticorps dirigés contre ces protéines.
PCT/JP2000/005356 1999-08-17 2000-08-10 Proteines humaines a domaines hydrophobes et adn codant pour ces proteines WO2001012660A2 (fr)

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US7241862B2 (en) 1998-05-15 2007-07-10 Genentech, Inc. Polypeptides that induce cell proliferation or induce fetal hemoglobin
EP1688430A3 (fr) * 1999-03-23 2006-11-02 Genentech, Inc. Polypeptides sécrétés et transmembranaires ainsi que les acides nucléiques codant pour ceux-ci
EP1396543A2 (fr) * 1999-07-08 2004-03-10 Research Association for Biotechnology Amorces pour la synthèse de cADN de pleine longueur et leur utilisation
EP1396543A3 (fr) * 1999-07-08 2004-03-31 Research Association for Biotechnology Amorces pour la synthèse de cADN de pleine longueur et leur utilisation
US7235632B1 (en) * 1999-11-12 2007-06-26 Commissariat A L'energie Atomique Isolated mammalian protein present at the surface of all lymphoid progenitor cells and all mature NK cells and uses thereof
WO2001051635A3 (fr) * 2000-01-13 2002-05-02 Genentech Inc Nouveaux polypeptides stra6
US7855278B2 (en) 2000-01-13 2010-12-21 Genentech, Inc. Antibodies to Stra6 polypeptides
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US7939650B2 (en) 2000-01-13 2011-05-10 Genentech, Inc. Stra6 polypeptides
WO2001051635A2 (fr) * 2000-01-13 2001-07-19 Genentech, Inc. Nouveaux polypeptides stra6
US7173115B2 (en) 2000-01-13 2007-02-06 Genentech, Inc. Stra6 polypeptides
WO2002077027A1 (fr) * 2000-03-23 2002-10-03 Curagen Corporation Proteine humaine de type stra6 et acides nucleiques codant cette proteine
WO2002006312A3 (fr) * 2000-07-13 2003-03-20 Novartis Ag Gene associe a une maladie
WO2002006312A2 (fr) * 2000-07-13 2002-01-24 Novartis Ag Gene associe a une maladie
WO2002006479A3 (fr) * 2000-07-14 2003-07-17 Max Planck Gesellschaft Sequences d'adn provoquant l'apoptose
WO2002006479A2 (fr) * 2000-07-14 2002-01-24 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Sequences d'adn provoquant l'apoptose
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AU6321400A (en) 2001-03-13

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