JP2001224379A - HUMAN PROTEIN AND cDNA [9] - Google Patents
HUMAN PROTEIN AND cDNA [9]Info
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- JP2001224379A JP2001224379A JP2000035899A JP2000035899A JP2001224379A JP 2001224379 A JP2001224379 A JP 2001224379A JP 2000035899 A JP2000035899 A JP 2000035899A JP 2000035899 A JP2000035899 A JP 2000035899A JP 2001224379 A JP2001224379 A JP 2001224379A
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】この出願の発明は、精製ヒト
蛋白質、この蛋白質をコードしているＤＮＡ断片、この
ＤＮＡ断片の発現ベクター、この発現ベクターにより形
質転換した各種の細胞、およびこの蛋白質に対する抗体
に関するものである。この発明の蛋白質は、医薬品とし
て、あるいはこの蛋白質に対する抗体を作製するための
抗原として用いることができる。また、この蛋白質は、
細胞内蛋白質ネットワ−クを解明するための研究試薬と
して、あるいは低分子医薬と結合する蛋白質をスクリー
ニングするための蛋白質源として用いることができる。
この発明のヒトｃＤＮＡは、遺伝子診断用プローブや遺
伝子治療用遺伝子源として用いることができる。また、
このｃＤＮＡがコードしている蛋白質を大量生産するた
めの遺伝子源として用いることができる。これらのＤＮ
Ａをインビトロ翻訳あるいは宿主細胞内で発現しうる発
現ベクターは、この発明の蛋白質をインビトロであるい
は各種の宿主細胞内で生産するのに用いることができ
る。これらの遺伝子を導入して蛋白質を過剰発現させた
細胞は、対応するレセプターやリガンドの検出、新しい
低分子医薬のスクリーニングなどに利用できる。この発
明の蛋白質に対する抗体は、蛋白質を精製するための手
段、あるいは細胞内における蛋白質の発現量や局在部位
を調べるのに用いられる。The present invention relates to a purified human protein, a DNA fragment encoding the protein, an expression vector for the DNA fragment, various cells transformed with the expression vector, and an antibody against the protein. It is about. The protein of the present invention can be used as a pharmaceutical or as an antigen for producing an antibody against the protein. Also, this protein
It can be used as a research reagent for elucidating an intracellular protein network or as a protein source for screening for a protein that binds to a low-molecular-weight drug.
The human cDNA of the present invention can be used as a probe for gene diagnosis or a gene source for gene therapy. Also,
It can be used as a gene source for mass-producing the protein encoded by this cDNA. These DNs
An expression vector capable of in vitro translation or expression of A in a host cell can be used for producing the protein of the present invention in vitro or in various host cells. Cells into which these genes have been introduced to overexpress proteins can be used for detection of corresponding receptors and ligands, screening of new low-molecular-weight drugs, and the like. The antibody against the protein of the present invention is used for purifying the protein or for examining the expression level and localization of the protein in cells.
【０００２】[0002]
【従来の技術】ヒト蛋白質は、我々の身体を構成してい
る細胞の基本要素である。その中には、（１）細胞の形
態を維持したり、細胞内の物質輸送や細胞運動に関わっ
ている細胞骨格蛋白質、（２）細胞内の物質代謝に関与
する代謝酵素、（３）エネルギ−産生に関わる蛋白質、
（４）細胞の増殖・***に関わる情報伝達蛋白質、
（５）蛋白質の合成に関わる翻訳関連蛋白質、（６）蛋
白質の分解に関わるプロテア−ゼ関連蛋白質、（７）ゲ
ノムの複製に関与する蛋白質、（８）遺伝子の転写に関
与する転写因子、（９）ｍＲＮＡのスプライシングに関
与する核蛋白質などが含まれる。これらの蛋白質は、ヒ
ト細胞の働きを解明する上で重要であるのみならず、医
薬品の開発においても有用である。これまで知られてい
る低分子化合物医薬の多くは、細胞内のある特定の蛋白
質と結合し、その蛋白質の働きを増強したり、阻止した
りすることによって、その薬効を表す。したがって、一
揃いのヒト蛋白質を持っていれば、これらの低分子医薬
をスクリ−ニングする際の有力な道具となる。BACKGROUND OF THE INVENTION Human proteins are a fundamental element of the cells that make up our bodies. These include (1) cytoskeletal proteins that maintain cell morphology and are involved in intracellular substance transport and cell movement, (2) metabolic enzymes involved in intracellular substance metabolism, and (3) energy -Proteins involved in production,
(4) signaling proteins involved in cell growth and division,
(5) a translation-related protein involved in protein synthesis, (6) a protease-related protein involved in protein degradation, (7) a protein involved in genome replication, (8) a transcription factor involved in gene transcription, ( 9) Includes nuclear proteins involved in mRNA splicing. These proteins are not only important in elucidating the function of human cells, but also useful in drug development. Many of the low molecular compound drugs known so far exhibit their efficacy by binding to a specific protein in cells and enhancing or blocking the action of the protein. Therefore, having a complete set of human proteins is a powerful tool for screening these low-molecular-weight drugs.
【０００３】従来、ヒト蛋白質を得るには、ヒト組織や
培養細胞をすりつぶした後、各種の分離法を組み合わせ
て単一の蛋白質を精製する方法がとられてきた。これま
で知られている蛋白質のように、含有量が高く、活性が
分かっているものは、従来の方法で容易に単離精製でき
るが、まだ解析されていない蛋白質の多くは含量が低
く、かつその性質によっては単離するのが困難である。
また、ヒト組織の多くは入手困難である。したがって、
従来のように蛋白質を単離精製する方法では、ヒト蛋白
質を全てそろえることは不可能に近い。Hitherto, to obtain a human protein, a method has been adopted in which human tissues and cultured cells are ground and then a single protein is purified by combining various separation methods. Proteins with a high content and known activity, such as those known so far, can be easily isolated and purified by conventional methods, but many proteins that have not yet been analyzed have a low content, and It is difficult to isolate depending on its properties.
Also, many human tissues are difficult to obtain. Therefore,
With conventional methods for isolating and purifying proteins, it is almost impossible to prepare all human proteins.
【０００４】一方、ヒト蛋白質の構造情報は、ヒトゲノ
ムＤＮＡに書かれているので、この情報をすべて読み取
れば、全ヒト蛋白質の一次構造を推定することができ
る。ヒトゲノムプロジェクトの目的の一つはここにあ
る。ただ、ゲノム解読の結果得られるのは、ＤＮＡ配列
情報だけであり、蛋白質そのものは得られない。細胞内
では、ゲノムの情報はまずｍＲＮＡに転写され、ｍＲＮ
Ａの配列情報を翻訳して蛋白質が合成される。したがっ
て、このｍＲＮＡを鋳型にして作製したｃＤＮＡが合成
できれば、このｃＤＮＡを用いて対応する蛋白質も合成
することが可能となる。そこで、各種細胞から単離した
ｍＲＮＡを鋳型にして、ｃＤＮＡを合成し、ｃＤＮＡの
部分塩基配列を決定するいわゆるＥＳＴプロジェクトが
進行している。[0004] On the other hand, since the structural information of human proteins is written in human genomic DNA, the primary structure of all human proteins can be estimated by reading all this information. This is one of the goals of the Human Genome Project. However, as a result of genome decoding, only the DNA sequence information is obtained, and the protein itself cannot be obtained. In cells, genomic information is first transcribed into mRNA,
The protein is synthesized by translating the sequence information of A. Therefore, if a cDNA prepared using this mRNA as a template can be synthesized, a corresponding protein can also be synthesized using the cDNA. Therefore, a so-called EST project for synthesizing cDNA using mRNA isolated from various cells as a template and determining a partial base sequence of cDNA is in progress.
【０００５】[0005]
【発明が解決しようとする課題】蛋白質の取得を目的と
する場合、ｃＤＮＡに要求される必須要件は、蛋白質の
翻訳領域を全て含んでいること、いわゆる完全長ｃＤＮ
Ａであることである。しかしながら、従来法で合成した
ｃＤＮＡは、完全長である割合は低く、得られたものが
完全長かどうかを判定することも困難である。すなわ
ち、ＥＳＴとして知られているものの多くは蛋白質の翻
訳領域の一部のみ含んでいるｃＤＮＡ断片である。In order to obtain a protein, an essential requirement for a cDNA is that it includes all of the protein's translation region, that is, a so-called full-length cDN.
A. However, the ratio of cDNA synthesized by the conventional method to full length is low, and it is difficult to determine whether the obtained cDNA is full length. That is, most of what is known as ESTs are cDNA fragments containing only a part of the protein translation region.
【０００６】これに対して、この出願の発明者らは、独
自の完全長ｃＤＮＡ合成技術を完成させている（Kato,
S. et al., Gene 150:243-250, 1994）。そしてこの技
術で合成したヒト完全長ｃＤＮＡクロ−ンを解析するこ
とにより、ヒト蛋白質を完全長ｃＤＮＡの形で取得する
ことが可能となった。この技術を用いてヒト完全長ｃＤ
ＮＡをすべてクロ−ン化し、ヒト蛋白質バンクを作製す
ることが望まれている。In contrast, the inventors of the present application have completed a unique full-length cDNA synthesis technique (Kato,
S. et al., Gene 150: 243-250, 1994). By analyzing human full-length cDNA clones synthesized by this technique, it became possible to obtain human proteins in the form of full-length cDNA. Using this technique, human full-length cD
It has been desired to clone all NA to prepare a human protein bank.
【０００７】また、これまでのヒト疾患に関する研究の
結果、ほとんどの病気は何らかの形で遺伝子に異常があ
るために引き起こされることが明らかになりつつある。
これらの病気を治療するためには、異常な遺伝子の替わ
りに正常な遺伝子を導入する遺伝子治療が有望視されて
いる。この際も、ヒトの完全長ｃＤＮＡは、遺伝子治療
用の遺伝子源として用いることができる。[0007] As a result of research on human diseases, it is becoming clear that most diseases are caused by some form of genetic abnormality.
In order to treat these diseases, gene therapy in which a normal gene is introduced instead of an abnormal gene is expected to be promising. In this case, the human full-length cDNA can be used as a gene source for gene therapy.
【０００８】この出願の発明は、以上のとおりの事情に
鑑みてなされたものであって、新規の精製ヒト蛋白質、
この蛋白質をコードするＤＮＡ断片、このＤＮＡ断片の
発現ベクター、この発現ベクターにより形質転換された
細胞およびこの蛋白質に対する抗体を提供することを課
題としている。[0008] The invention of this application has been made in view of the circumstances described above, and comprises a novel purified human protein,
It is an object of the present invention to provide a DNA fragment encoding the protein, an expression vector for the DNA fragment, a cell transformed with the expression vector, and an antibody against the protein.
【０００９】[0009]
【課題を解決するための手段】この出願は、前記の課題
を解決するものとして、以下の(1)〜(7)の発明を提供す
る。 (1) 配列番号２、４、６、８、１０、１２、１４、１
６、１８または２０のいずれかのアミノ酸配列を有する
精製ヒト蛋白質。 (2) 前記発明(1)の蛋白質をコードするＤＮＡ断片。 (3) 前記発明(1)の蛋白質をコードするヒトｃＤＮＡで
あって、１、３、５、７、９、１１、１３、１５、１７
または１９の翻訳領域の塩基配列を有するＤＮＡ断片。 (4) 配列番号１、３、５、７、９、１１、１３、１
５、１７または１９のいずれかの塩基配列からなる前記
発明(3)のＤＮＡ断片。 (5) 前記発明(2)から(4)のいずれかのＤＮＡ断片をイ
ンビトロ翻訳あるいは宿主細胞内で発現しうる発現ベク
ター。 (6) 前記発明(5)の発現ベクターによる形質転換体であ
って、前記発明(1)の蛋白質を生産しうる形質転換細
胞。 (7) 前記発明(1)の蛋白質に対する抗体。This application provides the following inventions (1) to (7) to solve the above-mentioned problems. (1) SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 1
A purified human protein having the amino acid sequence of any of 6, 18, or 20. (2) A DNA fragment encoding the protein of the invention (1). (3) A human cDNA encoding the protein of the invention (1), which comprises 1, 3, 5, 7, 9, 11, 13, 15, 17
Or a DNA fragment having the nucleotide sequence of 19 translation regions. (4) SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 1
The DNA fragment according to the invention (3), comprising the nucleotide sequence of any one of 5, 17 and 19. (5) An expression vector capable of in vitro translation or expression in a host cell of the DNA fragment according to any one of the inventions (2) to (4). (6) A transformant using the expression vector of the invention (5), which is capable of producing the protein of the invention (1). (7) An antibody against the protein of the invention (1).
【００１０】[0010]
【発明の実施の形態】前記発明(1)の蛋白質は、ヒトの
臓器、細胞株などから単離する方法、この出願によって
提供されるアミノ酸配列に基づき化学合成によってペプ
チドを調製する方法、あるいは前記発明(2)〜(4)のＤＮ
Ａ断片を用いて組換えＤＮＡ技術で生産する方法などに
より取得することができるが、組換えＤＮＡ技術で取得
する方法が好ましく用いられる。例えば、前記発明(3)
または(4)のＤＮＡ断片（ｃＤＮＡ）を有するベクター
からインビトロ転写によってＲＮＡを調製し、これを鋳
型としてインビトロ翻訳を行なうことによりインビトロ
で蛋白質を発現できる。また翻訳領域を公知の方法によ
り適当な発現ベクターに組換えることにより、大腸菌、
枯草菌等の原核細胞や、酵母、昆虫細胞、哺乳動物細
胞、植物細胞等の真核細胞で、ＤＮＡ断片がコードして
いる蛋白質を大量に発現させることができる。BEST MODE FOR CARRYING OUT THE INVENTION The protein of the invention (1) can be isolated from human organs, cell lines, etc., by preparing a peptide by chemical synthesis based on the amino acid sequence provided by this application, or Inventions (2) to (4) DN
Although it can be obtained by a method of producing the fragment A by recombinant DNA technology, a method of obtaining by recombinant DNA technology is preferably used. For example, the invention (3)
Alternatively, a protein can be expressed in vitro by preparing RNA by in vitro transcription from a vector having the DNA fragment (cDNA) of (4) and performing in vitro translation using this as a template. Also, by recombining the translation region into an appropriate expression vector by a known method, E. coli,
In prokaryotic cells such as Bacillus subtilis and eukaryotic cells such as yeast, insect cells, mammalian cells, and plant cells, a large amount of proteins encoded by DNA fragments can be expressed.
【００１１】前記発明(1)の蛋白質をインビトロ翻訳で
ＤＮＡ断片を発現させて生産させる場合には、例えば前
記発明(3)または(4)のＤＮＡ断片の翻訳領域を、ＲＮＡ
ポリメラーゼプロモーターを有するベクターに組換え、
プロモーターに対応するＲＮＡポリメラーゼを含む、ウ
サギ網状赤血球溶解物や小麦胚芽抽出物などのインビト
ロ翻訳系に添加すれば、前記発明(1)の蛋白質をインビ
トロで生産することができる。ＲＮＡポリメラーゼプロ
モーターとしては、Ｔ７、Ｔ３、ＳＰ６などが例示でき
る。これらのＲＮＡポリメラーゼプロモーターを含むベ
クターとしては、ｐＫＡ１、ｐＣＤＭ８、ｐＴ３／Ｔ７
１８、ｐＴ７／３ １９、ｐＢluescript IIなどが例示
できる。When the protein of the invention (1) is produced by expressing a DNA fragment by in vitro translation, for example, the translation region of the DNA fragment of the invention (3) or (4) may be replaced with RNA.
Recombined into a vector having a polymerase promoter,
The protein of the invention (1) can be produced in vitro by adding it to an in vitro translation system such as a rabbit reticulocyte lysate or a wheat germ extract containing an RNA polymerase corresponding to the promoter. Examples of the RNA polymerase promoter include T7, T3, SP6 and the like. Vectors containing these RNA polymerase promoters include pKA1, pCDM8, pT3 / T7
18, pT7 / 319, pBluescript II and the like.
【００１２】前記発明(1)の蛋白質を大腸菌などの微生
物でＤＮＡ断片を発現させて生産させる場合には、微生
物中で複製可能なオリジン、プロモーター、リボソーム
結合部位、ＤＮＡクローニング部位、ターミネーター等
を有する発現ベクターに、例えば前記発明(3)または(4)
のＤＮＡ断片の翻訳領域を組換えた発現ベクターを作成
し、この発現ベクターで宿主細胞を形質転換したのち、
得られた形質転換体を培養すれば、このＤＮＡ断片がコ
ードしている蛋白質を微生物内で大量生産することがで
きる。この際、任意の翻訳領域の前後に開始コドンと停
止コドンを付加して発現させれば、任意の領域を含む蛋
白質断片を得ることができる。あるいは、他の蛋白質と
の融合蛋白質として発現させることもできる。この融合
蛋白質を適当なプロテアーゼで切断することによってこ
のｃＤＮＡがコードする蛋白質部分のみを取得すること
もできる。大腸菌用発現ベクターとしては、ｐＵＣ系、
ｐＢluescript II、ｐＥＴ発現システム、ｐＧＥＸ発現
システムなどが例示できる。When the protein of the invention (1) is produced by expressing a DNA fragment in a microorganism such as Escherichia coli, it has an origin, a promoter, a ribosome binding site, a DNA cloning site, a terminator and the like which can be replicated in the microorganism. Expression vector, for example, the invention (3) or (4)
After preparing an expression vector in which the translation region of the DNA fragment has been recombined and transforming a host cell with this expression vector,
By culturing the obtained transformant, the protein encoded by this DNA fragment can be mass-produced in a microorganism. At this time, a protein fragment containing an arbitrary region can be obtained by adding a start codon and a stop codon before and after an arbitrary translation region for expression. Alternatively, it can be expressed as a fusion protein with another protein. By cleaving this fusion protein with an appropriate protease, only the protein portion encoded by the cDNA can be obtained. Examples of expression vectors for Escherichia coli include the pUC system,
Examples include pBluescript II, pET expression system, pGEX expression system, and the like.
【００１３】前記発明(1)の蛋白質を、真核細胞でＤＮ
Ａ断片を発現させて生産させる場合には、例えば前記発
明(3)または(4)のＤＮＡ断片の翻訳領域を、プロモータ
ー、スプライシング領域、ポリ(A)付加部位等を有する
真核細胞用発現ベクターに組換え、真核細胞内に導入す
れば、前記発明(1)の蛋白質を真核細胞内で生産するこ
とができる。発現ベクターとしては、ｐＫＡ１、ｐＣＤ
Ｍ８、ｐＳＶＫ３、ｐＭＳＧ、ｐＳＶＬ、ｐＢＫ−ＣＭ
Ｖ、ｐＢＫ−ＲＳＶ、ＥＢＶベクター、ｐＲＳ、ｐＹＥ
Ｓ２などが例示できる。また、ｐＩＮＤ／Ｖ５−Ｈｉ
ｓ、ｐＦＬＡＧ−ＣＭＶ−２、ｐＥＧＦＰ−Ｎ１、ｐＥ
ＧＦＰ−Ｃ１などを発現ベクタ−として用いれば、Ｈｉ
ｓタグ、ＦＬＡＧタグ、ＧＦＰなど各種タグを付加した
融合蛋白質として発現させることもできる。真核細胞と
しては、サル腎臓細胞ＣＯＳ７、チャイニーズハムスタ
ー卵巣細胞ＣＨＯなどの哺乳動物培養細胞、出芽酵母、
***酵母、カイコ細胞、アフリカツメガエル卵細胞など
が一般に用いられるが、前記発明(1)の蛋白質を発現で
きるものであれば、いかなる真核細胞でもよい。発現ベ
クターを真核細胞に導入するには、電気穿孔法、リン酸
カルシウム法、リポソーム法、ＤＥＡＥデキストラン法
など公知の方法を用いることができる。[0013] The protein of the invention (1) can be used in a eukaryotic cell by DN.
When the A fragment is expressed and produced, for example, the translation region of the DNA fragment of the invention (3) or (4) may be a promoter, a splicing region, an expression vector for eukaryotic cells having a poly (A) addition site and the like. When the recombinant is introduced into eukaryotic cells, the protein of the invention (1) can be produced in eukaryotic cells. Examples of expression vectors include pKA1, pCD
M8, pSVK3, pMSG, pSVL, pBK-CM
V, pBK-RSV, EBV vector, pRS, pYE
S2 and the like can be exemplified. Also, pIND / V5-Hi
s, pFLAG-CMV-2, pEGFP-N1, pE
If GFP-C1 or the like is used as an expression vector, Hi
It can also be expressed as a fusion protein to which various tags such as s tag, FLAG tag, and GFP are added. Examples of eukaryotic cells include mammalian cultured cells such as monkey kidney cells COS7, Chinese hamster ovary cells CHO, budding yeast,
Fission yeast, silkworm cells, Xenopus egg cells and the like are generally used, and any eukaryotic cell may be used as long as it can express the protein of the invention (1). In order to introduce the expression vector into eukaryotic cells, known methods such as an electroporation method, a calcium phosphate method, a liposome method, and a DEAE dextran method can be used.
【００１４】前記発明(1)の蛋白質を原核細胞や真核細
胞で発現させたのち、培養物から目的蛋白質を単離精製
するためには、公知の分離操作を組み合わせて行うこと
ができる。例えば、尿素などの変性剤や界面活性剤によ
る処理、超音波処理、酵素消化、塩析や溶媒沈殿法、透
析、遠心分離、限外濾過、ゲル濾過、ＳＤＳ−ＰＡＧ
Ｅ、等電点電気泳動、イオン交換クロマトグラフィー、
疎水性クロマトグラフィー、アフィニティークロマトグ
ラフィー、逆相クロマトグラフィーなどがあげられる。After the protein of the invention (1) is expressed in prokaryotic or eukaryotic cells, the target protein can be isolated and purified from the culture by a combination of known separation procedures. For example, treatment with a denaturant such as urea or a surfactant, ultrasonic treatment, enzymatic digestion, salting out or solvent precipitation, dialysis, centrifugation, ultrafiltration, gel filtration, SDS-PAG
E, isoelectric focusing, ion exchange chromatography,
Examples include hydrophobic chromatography, affinity chromatography, and reverse phase chromatography.
【００１５】前記発明(1)の蛋白質には、配列番号２、
４、６、８、１０、１２、１４、１６、１８または２０
のアミノ酸配列のいかなる部分アミノ酸配列からなるペ
プチド断片（５アミノ酸残基以上）も含まれる。これら
のペプチド断片は抗体を作製するための抗原として用い
ることができる。また、前記発明(1)の蛋白質の多く
は、翻訳された後、細胞内で各種修飾を受ける。したが
って、これらの修飾された蛋白質も前記発明(1)の蛋白
質の範囲に含まれる。このような翻訳後修飾としては、
Ｎ末端メチオニンの脱離、Ｎ末端アセチル化、糖鎖付
加、細胞内プロテア−ゼによる限定分解、ミリストイル
化、イソプレニル化、リン酸化などが例示できる。The protein of the invention (1) includes SEQ ID NO: 2,
4, 6, 8, 10, 12, 14, 16, 18, or 20
And a peptide fragment (5 or more amino acid residues) consisting of any partial amino acid sequence of the above amino acid sequence. These peptide fragments can be used as antigens for producing antibodies. Many of the proteins of the invention (1) undergo various modifications in cells after being translated. Therefore, these modified proteins are also included in the scope of the protein of the invention (1). Such post-translational modifications include:
Examples include N-terminal methionine elimination, N-terminal acetylation, sugar chain addition, limited degradation by intracellular protease, myristoylation, isoprenylation, phosphorylation and the like.
【００１６】前記発明(2)〜(4)のＤＮＡ断片には、前記
(1)の蛋白質をコードするすべてのＤＮＡが含まれる。
このＤＮＡ断片は、化学合成による方法、ｃＤＮＡクロ
ーニングによる方法、ヒトゲノムライブラリーをスクリ
ーニングする方法などを用いて取得することができる。The DNA fragments of the inventions (2) to (4) include
All DNAs encoding the protein of (1) are included.
This DNA fragment can be obtained using a method based on chemical synthesis, a method based on cDNA cloning, a method for screening a human genomic library, and the like.
【００１７】前記発明(3)または(4)のＤＮＡ断片（ｃＤ
ＮＡ）は、例えばヒト細胞由来ｃＤＮＡライブラリーか
らクローン化することができる。ｃＤＮＡはヒト細胞か
ら抽出したポリ(A)+ＲＮＡを鋳型として合成する。ヒト
細胞としては、人体から手術などによって摘出されたも
のでも培養細胞でも良い。ｃＤＮＡは、岡山−Berg法
（Okayama, H. and Berg, P., Mol. Cell. Biol. 2:161
-170, 1982）、Gubler-Hoffman法（Gubler, U. and Hof
fman, J., Gene 25:263-269, 1983）などいかなる方法
を用いて合成してもよいが、完全長クローンを効率的に
得るためには、実施例にあげたようなキャッピング法
（Kato, S. et al., Gene 150:243-250, 1994）を用い
ることが望ましい。また市販のヒトｃＤＮＡライブラリ
ーを用いることもできる。ｃＤＮＡライブラリーから目
的のｃＤＮＡをクローン化するには、この出願によって
提供される前記発明(3)または(4)のｃＤＮＡ（配列番号
１、３、５、７、９、１１、１３、１５、１７または１
９）の任意部分の塩基配列に基づいてオリゴヌクレオチ
ドを合成し、これをプローブとして用いて、公知の方法
によりコロニーあるいはプラークハイブリダイゼーショ
ンによるスクリーニングを行えばよい。また、目的とす
るｃＤＮＡ断片の両末端にハイブリダイズするオリゴヌ
クレオチドを合成し、これをプライマーとして用いて、
ヒト細胞から単離したｍＲＮＡからＲＴ−ＰＣＲ法によ
り、前記発明(3)または(4)のｃＤＮＡ断片を調製するこ
ともできる。The DNA fragment of the invention (3) or (4) (cD
NA) can be cloned, for example, from a cDNA library derived from human cells. cDNA is synthesized using poly (A) + RNA extracted from human cells as a template. The human cells may be cells extracted from a human body by surgery or the like or cultured cells. The cDNA was prepared by the Okayama-Berg method (Okayama, H. and Berg, P., Mol. Cell. Biol. 2: 161
-170, 1982), Gubler-Hoffman method (Gubler, U. and Hof
fman, J., Gene 25: 263-269, 1983), but in order to obtain a full-length clone efficiently, the capping method (Kato , S. et al., Gene 150: 243-250, 1994). A commercially available human cDNA library can also be used. To clone a cDNA of interest from a cDNA library, the cDNA of the invention (3) or (4) provided by this application (SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17 or 1
Oligonucleotides may be synthesized based on the base sequence of any part of 9), and screening may be performed by colony or plaque hybridization by a known method using this as a probe. In addition, an oligonucleotide that hybridizes to both ends of the cDNA fragment of interest is synthesized, and using this as a primer,
The cDNA fragment of the invention (3) or (4) can also be prepared from mRNA isolated from human cells by RT-PCR.
【００１８】前記発明(3)のＤＮＡ断片は、配列番号
１、３、５、７、９、１１、１３、１５、１７または１
９の翻訳領域（Open Reading Frame：ＯＲＦ）の塩基配
列を有するｃＤＮＡであり、前記発明(4)のＤＮＡ断片
は、配列番号１、３、５、７、９、１１、１３、１５、
１７または１９のいずれかの塩基配列からなるｃＤＮＡ
である。それぞれのクローン番号（ＨＰ番号）、ｃＤＮ
Ａクローンが得られた細胞、ｃＤＮＡの全塩基数、コー
ドしている蛋白質のアミノ酸残基数をそれぞれ表１にま
とめて示した。[0018] The DNA fragment of the invention (3) may be any of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, or 1
9 is a cDNA having a nucleotide sequence of 9 translation regions (Open Reading Frame: ORF), and the DNA fragment of the invention (4) is SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15,
CDNA consisting of either 17 or 19 nucleotide sequence
It is. Each clone number (HP number), cDN
Table 1 summarizes the cells from which the A clone was obtained, the total number of bases in the cDNA, and the number of amino acid residues in the encoded protein.
【００１９】[0019]
【表１】 [Table 1]
【００２０】なお、配列番号１、３、５、７、９、１
１、１３、１５、１７または１９のいずれかの塩基配列
に基づいて合成したオリゴヌクレオチドプローブを用い
て、表１に示したヒト細胞株やヒト組織から作製したｃ
ＤＮＡライブラリーをスクリーニングすることにより、
前記発明(3)および(4)のｃＤＮＡと同一のクローンを容
易に得ることができる。In addition, SEQ ID NOs: 1, 3, 5, 7, 9, 1
Using an oligonucleotide probe synthesized based on any of the base sequences of 1, 13, 15, 17 or 19, c prepared from a human cell line or a human tissue shown in Table 1
By screening a DNA library,
A clone identical to the cDNA of the inventions (3) and (4) can be easily obtained.
【００２１】また、一般にヒト遺伝子は個体差による多
型が頻繁に認められる。従って配列番号１１から３０に
おいて、１または複数個のヌクレオチドの付加、欠失お
よび／または他のヌクレオチドによる置換がなされてい
るｃＤＮＡもこの発明の範囲に含まれる。Generally, polymorphisms due to individual differences are frequently observed in human genes. Accordingly, cDNAs in which one or more nucleotides are added, deleted and / or substituted by other nucleotides in SEQ ID NOS: 11 to 30 are also included in the scope of the present invention.
【００２２】同様に、これらの変更によって生じる１ま
たは複数個のアミノ酸の付加、欠失および／または他の
アミノ酸による置換がなされている蛋白質も、配列番号
１から１０のアミノ酸配列を有するそれぞれの蛋白質の
活性を有する限り、この発明の範囲に含まれる。Similarly, proteins in which one or more amino acids are added, deleted and / or substituted by other amino acids resulting from these changes are also proteins having the amino acid sequences of SEQ ID NOS: 1 to 10. As long as it has the activity of, it is included in the scope of the present invention.
【００２３】前記発明（3）および(4)のＤＮＡ断片に
は、配列番号１１から３０の塩基配列のいかなる部分塩
基配列からなるＤＮＡ断片（10bp以上）も含まれる。ま
た、センス鎖およびアンチセンス鎖からなるＤＮＡ断片
もこの範囲に含まれる。これらのＤＮＡ断片は遺伝子診
断用のプローブとして用いることができる。The DNA fragments of the inventions (3) and (4) include DNA fragments (10 bp or more) consisting of any partial nucleotide sequence of the nucleotide sequences of SEQ ID NOS: 11 to 30. Further, a DNA fragment consisting of a sense strand and an antisense strand is also included in this range. These DNA fragments can be used as probes for gene diagnosis.
【００２４】前記発明(7)の抗体は、前記発明(1)の蛋白
質を抗原として用いて動物を免役した後、血清から得る
ことが出きる。抗原としては配列番号１から１０のアミ
ノ酸配列に基づいて化学合成したペプチドや、真核細胞
や原核細胞で発現させた蛋白質を用いることが出きる。
あるいは、上記の真核細胞用発現ベクターを注射や遺伝
子銃によって、動物の筋肉や皮膚に導入した後、血清を
採取することによって作製することができる（例えば、
特開平７−３１３１８７号公報記載の方法）。動物とし
ては、マウス、ラット、ウサギ、ヤギ、ニワトリなどが
用いられる。免疫した動物の脾臓から採取したＢ細胞を
ミエロ−マと融合させてハイブリド−マを作製すれば、
前記発明(1)の蛋白質に対するモノクロ−ナル抗体を産
生することができる。The antibody of the invention (7) can be obtained from serum after immunization of an animal using the protein of the invention (1) as an antigen. As the antigen, a peptide chemically synthesized based on the amino acid sequence of SEQ ID NOS: 1 to 10 or a protein expressed in eukaryotic cells or prokaryotic cells can be used.
Alternatively, it can be prepared by introducing the above eukaryotic cell expression vector into an animal muscle or skin by injection or gene gun, and then collecting serum (for example,
Method described in JP-A-7-313187). As animals, mice, rats, rabbits, goats, chickens and the like are used. By fusing B cells collected from the spleen of the immunized animal with myeloma to produce a hybridoma,
A monoclonal antibody against the protein of the invention (1) can be produced.
【００２５】[0025]
【実施例】次に実施例を示してこの出願の発明をさらに
詳細かつ具体的に説明するが、この出願の発明は以下の
例によって限定されるものではない。なお、以下の実施
例において、ＤＮＡの組換えに関する基本的な操作およ
び酵素反応は、文献（"Molecular Cloning. A Laborato
ry Manual", Cold Spring Harbor Laboratory, 1989）
の記載に方従った。制限酵素および各種修飾酵素は特に
記載の無い場合は宝酒造社製のものを用いた。各酵素反
応の緩衝液組成、並びに反応条件は付属の説明書に従っ
た。ｃＤＮＡ合成は文献（Kato, S. et al., Gene 150:
243-250, 1994）の記載に従った。 実施例１：ｃＤＮＡクロ−ニング ｃＤＮＡライブラリーとして、ヒト完全長ｃＤＮＡライ
ブラリ−（ＷＯ９７／３３９９３、ＷＯ９８／１１２１
７、ＷＯ９８／２１３２８記載）を用いた。個々のライ
ブラリーから完全長ｃＤＮＡクローンを選択し、その全
塩基配列決定を行った。得られたクロ−ン（Ａ）〜
（Ｊ）の詳細は以下のとおりである。 （Ａ） ＨＰ１０５５２ ヒト骨肉腫細胞株Ｓａｏｓ−２ｃＤＮＡライブラリーか
ら得られたクローンＨＰ１０５５２のｃＤＮＡインサー
トの全塩基配列を決定したところ、１３２ｂｐの５’非
翻訳領域、７３８ｂｐのＯＲＦ、４８４ｂｐの３’非翻
訳領域からなる構造を有していた（配列番号１）。ＯＲ
Ｆは２４５アミノ酸残基（配列番号２）からなる蛋白質
をコードしており、インビトロ翻訳の結果、ＯＲＦから
予想される分子量２７，６０９より大きい３７ｋＤａの
翻訳産物が生成した（実施例２）。この蛋白質とＧＦＰ
との融合蛋白質は、凝集塊として発現が認められた（実
施例４）。Next, the present invention will be described in more detail and specifically with reference to examples, but the invention of this application is not limited by the following examples. In the following examples, basic operations and enzymatic reactions relating to DNA recombination are described in the literature ("Molecular Cloning. A Laborato
ry Manual ", Cold Spring Harbor Laboratory, 1989)
Was followed. Restriction enzymes and various modifying enzymes used were those manufactured by Takara Shuzo Co., Ltd. unless otherwise specified. The buffer composition and reaction conditions for each enzyme reaction were in accordance with the attached instructions. cDNA synthesis is described in the literature (Kato, S. et al., Gene 150:
243-250, 1994). Example 1: cDNA cloning As a cDNA library, a human full-length cDNA library (WO97 / 33993, WO98 / 1121)
7, WO98 / 21328). A full-length cDNA clone was selected from each library, and its entire nucleotide sequence was determined. The resulting clone (A)
Details of (J) are as follows. (A) HP10552 The entire nucleotide sequence of the cDNA insert of clone HP10552 obtained from the human osteosarcoma cell line Saos-2 cDNA library was determined. It had a structure consisting of regions (SEQ ID NO: 1). OR
F encodes a protein consisting of 245 amino acid residues (SEQ ID NO: 2). As a result of in vitro translation, a translation product of 37 kDa larger than the molecular weight of 27,609 predicted from the ORF was generated (Example 2). This protein and GFP
The fusion protein with was expressed as an aggregate (Example 4).
【００２６】クロ−ン（Ａ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、ＥＳＴの中に９０
％以上の相同性を有するもの（例えば、アクセション番
号ＡＩ９２９０８９）が登録されていたが、部分配列な
のでクロ−ン（Ａ）がコ−ドする蛋白質と同じ蛋白質を
コードしているかどうかは判定できない。 （Ｂ） ＨＰ１０５５３ ヒトフィブロサルコ−マ細胞株ＨＴ−１０８０ｃＤＮＡ
ライブラリーから得られたクローンＨＰ１０５５３のｃ
ＤＮＡインサートの全塩基配列を決定したところ、１６
９ｂｐの５’非翻訳領域、３３３ｂｐのＯＲＦ、１５１
ｂｐの３’非翻訳領域からなる構造を有していた（配列
番号３）。ＯＲＦは１１０アミノ酸残基（配列番号４）
からなる蛋白質をコードしており、インビトロ翻訳の結
果、ＯＲＦから予想される分子量１２，３８７より大き
い１４ｋＤａの翻訳産物が生成した（実施例２）。この
蛋白質とＧＦＰとの融合蛋白質は、細胞全体に発現が認
められた（実施例４）。When GenBank was searched using the base sequence of the clone (A) cDNA, 90% was found in the EST.
% (For example, accession number AI92989) has been registered. However, since it is a partial sequence, it cannot be determined whether clone (A) encodes the same protein as the protein encoded. . (B) HP10553 human fibrosarcoma cell line HT-1080 cDNA
C of clone HP10553 obtained from library
When the total nucleotide sequence of the DNA insert was determined, 16
9 bp 5 'untranslated region, 333 bp ORF, 151
bp 3 ′ untranslated region (SEQ ID NO: 3). ORF is 110 amino acid residues (SEQ ID NO: 4)
And a translation product of 14 kDa, which is larger than the molecular weight predicted from the ORF of 12,387, was generated as a result of in vitro translation (Example 2). Expression of the fusion protein of this protein and GFP was observed in the whole cell (Example 4).
【００２７】クロ−ン（Ｂ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、ＥＳＴの中に、９
０％以上の相同性を有するもの（例えば、アクセション
番号Ｚ４３８７１）が登録されていたが、部分配列なの
でクロ−ン（Ｂ）がコ−ドする蛋白質と同じ蛋白質をコ
ードしているかどうかは判定できない。 （Ｃ） ＨＰ１０５５８ ヒト骨肉腫細胞株Ｓａｏｓ−２ｃＤＮＡライブラリーか
ら得られたクローンＨＰ１０５５８のｃＤＮＡインサー
トの全塩基配列を決定したところ、３９ｂｐの５’非翻
訳領域、３７２ｂｐのＯＲＦ、２３２ｂｐの３’非翻訳
領域からなる構造を有していた（配列番号５）。ＯＲＦ
は１２３アミノ酸残基（配列番号６）からなる蛋白質を
コードしていた。インビトロ翻訳の結果、ＯＲＦから予
想される分子量１４，２２５より大きい２０ｋＤａの翻
訳産物が生成した（実施例２）。この蛋白質とＧＦＰと
の融合蛋白質は、核小体に局在が認められた（実施例
４）。When GenBank was searched using the base sequence of clone (B) cDNA, 9% was found in EST.
A protein having a homology of 0% or more (eg, Accession No. Z43871) has been registered, but since it is a partial sequence, it is determined whether clone (B) encodes the same protein as the protein encoded. Can not. (C) HP10558 The entire nucleotide sequence of the cDNA insert of clone HP10558, obtained from the human osteosarcoma cell line Saos-2 cDNA library, was determined. It had a structure consisting of regions (SEQ ID NO: 5). ORF
Encoded a protein consisting of 123 amino acid residues (SEQ ID NO: 6). As a result of the in vitro translation, a translation product of 20 kDa was generated which was larger than the molecular weight predicted from the ORF of 14,225 (Example 2). The fusion protein of this protein and GFP was localized in the nucleolus (Example 4).
【００２８】クロ−ン（Ｃ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、ＥＳＴの中に、９
０％以上の相同性を有するもの（例えば、アクセション
番号ＡＡ３２７０５６）が登録されていたが、部分配列
なのでクロ−ン（Ｃ）がコ−ドする蛋白質と同じ蛋白質
をコードしているかどうかは判定できない。 （Ｄ） ＨＰ１０５５９ ヒト骨肉腫細胞株Ｓａｏｓ−２ｃＤＮＡライブラリーか
ら得られたクローンＨＰ１０５５９のｃＤＮＡインサー
トの全塩基配列を決定したところ、３０５ｂｐの５’非
翻訳領域、７１４ｂｐのＯＲＦ、２７４ｂｐの３’非翻
訳領域からなる構造を有していた（配列番号７）。ＯＲ
Ｆは２３７アミノ酸残基（配列番号８）からなる蛋白質
をコードしていた。この蛋白質とＧＦＰとの融合蛋白質
は、核に局在が認められた（実施例４）。When GenBank was searched using the nucleotide sequence of the clone (C) cDNA, 9% was found in the EST.
A protein having a homology of 0% or more (eg, Accession No. AA327056) was registered, but since it is a partial sequence, it is determined whether clone (C) encodes the same protein as the protein encoded. Can not. (D) HP10559 The entire nucleotide sequence of the cDNA insert of clone HP10559 obtained from the human osteosarcoma cell line Saos-2 cDNA library was determined. It had a structure consisting of regions (SEQ ID NO: 7). OR
F coded for a protein consisting of 237 amino acid residues (SEQ ID NO: 8). The fusion protein of this protein and GFP was localized in the nucleus (Example 4).
【００２９】この蛋白質のアミノ酸配列を用いてプロテ
インデータベースを検索したところ、ヒト仮想蛋白質Ｋ
ＩＡＡ０２７６（アクセション番号ＢＡＡ１３４０５）
と類似性を有していた。図１に、クロ−ン（Ｄ）がコ−
ドするヒト蛋白質と、ヒト仮想蛋白質ＫＩＡＡ０２７６
のアミノ酸配列の比較を示す。−はギャップを、＊はこ
の発明の蛋白質と同一アミノ酸残基を、．はこの発明の
蛋白質と類似アミノ酸残基をそれぞれ表す。全領域にわ
たって、６９．６％の相同性を有していた。When a protein database was searched using the amino acid sequence of this protein, human hypothetical protein K
IAA0276 (Accession number BAA13405)
And similarities. In FIG. 1, the clone (D) is
Human protein KIAA0276
1 shows a comparison of the amino acid sequences of -Indicates a gap, * indicates the same amino acid residue as the protein of the present invention,. Represents a similar amino acid residue to the protein of the present invention. It had 69.6% homology over the entire region.
【００３０】クロ−ン（Ｄ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、９０％以上の相同
性を有するもの（アクセション番号Ａ７５３３４、特許
ＷＯ９４０１５４８）が、またＥＳＴの中に、９０％以
上の相同性を有するもの（例えば、アクセション番号Ａ
Ａ０９９９６６）が登録されていたが、いずれも部分配
列なのでクロ−ン（Ｄ）がコ−ドする蛋白質と同じ蛋白
質をコードしているかどうかは判定できない。 （Ｅ） ＨＰ１０５６０ ヒト骨肉腫細胞株Ｓａｏｓ−２ｃＤＮＡライブラリーか
ら得られたクローンＨＰ１０５６０のｃＤＮＡインサー
トの全塩基配列を決定したところ、１４７ｂｐの５’非
翻訳領域、３２４ｂｐのＯＲＦ、４４５ｂｐの３’非翻
訳領域からなる構造を有していた（配列番号９）。ＯＲ
Ｆは１０７アミノ酸残基（配列番号１０）からなる蛋白
質をコードしていた。この蛋白質とＧＦＰとの融合蛋白
質は、細胞全体に認められた（実施例４）。When GenBank was searched using the nucleotide sequence of clone (D) cDNA, it was found that those having 90% or more homology (Accession No. A75334, Patent WO9401548) had 90% homology in EST. Those having the above homology (for example, accession number A
A099966) has been registered, but since all of them are partial sequences, it cannot be determined whether clone (D) encodes the same protein as the encoded protein. (E) HP10560 The entire nucleotide sequence of the cDNA insert of clone HP10560, obtained from the human osteosarcoma cell line Saos-2 cDNA library, was determined. It had a structure consisting of regions (SEQ ID NO: 9). OR
F coded for a protein consisting of 107 amino acid residues (SEQ ID NO: 10). The fusion protein of this protein and GFP was found in the whole cell (Example 4).
【００３１】クロ−ン（Ｅ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、ＥＳＴの中に、９
０％以上の相同性を有するもの（例えば、アクセション
番号Ｃ１７８７０）が登録されていたが、部分配列なの
でクロ−ン（Ｅ）がコ−ドする蛋白質と同じ蛋白質をコ
ードしているかどうかは判定できない。 （Ｆ） ＨＰ１０５６１ ヒト胃癌ｃＤＮＡライブラリーから得られたクローンＨ
Ｐ１０５６１のｃＤＮＡインサートの全塩基配列を決定
したところ、５０ｂｐの５’非翻訳領域、６８１ｂｐの
ＯＲＦ、２７１ｂｐの３’非翻訳領域からなる構造を有
していた（配列番号１１）。ＯＲＦは２２６アミノ酸残
基（配列番号１２）からなる蛋白質をコードしており、
インビトロ翻訳の結果、ＯＲＦから予想される分子量２
２，５８１より大きい２９ｋＤａの翻訳産物が生成した
（実施例２）。この蛋白質とＧＦＰとの融合蛋白質は、
核小体に局在が認められた（実施例４）。When GenBank was searched using the nucleotide sequence of clone (E) cDNA, 9% was found in EST.
A protein having a homology of 0% or more (for example, accession number C17870) was registered. However, since it is a partial sequence, it is determined whether clone (E) encodes the same protein as the protein encoded. Can not. (F) HP10561 Clone H obtained from human gastric cancer cDNA library
When the entire base sequence of the cDNA insert of P10561 was determined, it had a structure consisting of a 50 bp 5 ′ untranslated region, a 681 bp ORF, and a 271 bp 3 ′ untranslated region (SEQ ID NO: 11). ORF encodes a protein consisting of 226 amino acid residues (SEQ ID NO: 12),
As a result of in vitro translation, the expected molecular weight of ORF 2
A 29 kDa translation product larger than 2,581 was produced (Example 2). The fusion protein of this protein and GFP is
Localization was observed in the nucleolus (Example 4).
【００３２】クロ−ン（Ｆ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、ＥＳＴの中に、９
０％以上の相同性を有するもの（例えば、アクセション
番号Ｗ８４３５３）が登録されていたが、部分配列なの
でクロ−ン（Ｆ）がコ−ドする蛋白質と同じ蛋白質をコ
ードしているかどうかは判定できない。 （Ｇ） ＨＰ１０５６２ ヒト骨肉腫細胞株Ｓａｏｓ−２ｃＤＮＡライブラリーか
ら得られたクローンＨＰ１０５６２のｃＤＮＡインサー
トの全塩基配列を決定したところ、２６７ｂｐの５’非
翻訳領域、１１８８ｂｐのＯＲＦ、２９８ｂｐの３’非
翻訳領域からなる構造を有していた（配列番号１３）。
ＯＲＦは３９５アミノ酸残基（配列番号１４）からなる
蛋白質をコードしており、インビトロ翻訳の結果、ＯＲ
Ｆから予想される分子量４３，４０５より大きい４８ｋ
Ｄａの翻訳産物が生成した（実施例２）。この蛋白質と
ＧＦＰとの融合蛋白質は、粒子状の発現と細胞全体に弱
く発現が認められた（実施例４）。When GenBank was searched using the nucleotide sequence of clone (F) cDNA, 9% was found in EST.
A protein having a homology of 0% or more (eg, accession number W84353) has been registered, but since it is a partial sequence, it is determined whether clone (F) encodes the same protein as the protein encoded. Can not. (G) HP10562 The entire nucleotide sequence of the cDNA insert of clone HP10562 obtained from the human osteosarcoma cell line Saos-2 cDNA library was determined. It had a structure consisting of regions (SEQ ID NO: 13).
ORF encodes a protein consisting of 395 amino acid residues (SEQ ID NO: 14).
48k larger than the expected molecular weight of 43,405 from F
A translation product of Da was produced (Example 2). The fusion protein of this protein and GFP was found to be expressed in the form of particles and weakly in the whole cell (Example 4).
【００３３】この蛋白質のアミノ酸配列を用いてプロテ
インデータベースを検索したところ、ヒト塩基性ロイシ
ンジッパー蛋白質ＬＺＩＰ（アクセション番号ＢＡＡ１
３４０５）と類似性を有していた。図２に、クロ−ン
（Ｇ）がコ−ドするヒト蛋白質と、ヒト塩基性ロイシン
ジッパー蛋白質ＬＺＩＰのアミノ酸配列の比較を示す。
−はギャップを、＊はこの発明の蛋白質と同一アミノ酸
残基を、．はこの発明の蛋白質と類似アミノ酸残基をそ
れぞれ表す。中間領域２０６アミノ酸残基において、４
３．７％の相同性を有していた。When a protein database was searched using the amino acid sequence of this protein, the human basic leucine zipper protein LZIP (accession number BAA1
3405). FIG. 2 shows a comparison of the amino acid sequences of the human protein encoded by clone (G) and the human basic leucine zipper protein LZIP.
-Indicates a gap, * indicates the same amino acid residue as the protein of the present invention,. Represents a similar amino acid residue to the protein of the present invention. At 206 amino acid residues in the middle region, 4
It had 3.7% homology.
【００３４】クロ−ン（Ｇ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、ＥＳＴの中に、９
０％以上の相同性を有するもの（例えば、アクセション
番号ＡＡ２０３１１０）が登録されていたが、部分配列
なのでクロ−ン（Ｇ）がコ−ドする蛋白質と同じ蛋白質
をコードしているかどうかは判定できない。 （Ｈ） ＨＰ１０５６４ ヒト骨肉腫細胞株Ｓａｏｓ−２ｃＤＮＡライブラリーか
ら得られたクローンＨＰ１０５６４のｃＤＮＡインサー
トの全塩基配列を決定したところ、５３ｂｐの５’非翻
訳領域、６９ｂｐのＯＲＦ、５４６ｂｐの３’非翻訳領
域からなる構造を有していた（配列番号１７）。ＯＲＦ
は２２アミノ酸残基（配列番号１６）からなる蛋白質を
コードしていた。この蛋白質とＧＦＰとの融合蛋白質
は、細胞全体に発現が認められた（実施例４）。When GenBank was searched using the nucleotide sequence of the clone (G) cDNA, 9% was found in the EST.
A protein having a homology of 0% or more (eg, Accession No. AA203110) was registered, but since it is a partial sequence, it is determined whether clone (G) encodes the same protein as the protein encoded. Can not. (H) HP10564 The complete nucleotide sequence of the cDNA insert of clone HP10564 obtained from the human osteosarcoma cell line Saos-2 cDNA library was determined. The 5bp untranslated region of 53bp, the ORF of 69bp and the 3 'untranslated of 546bp It had a structure consisting of regions (SEQ ID NO: 17). ORF
Encoded a protein consisting of 22 amino acid residues (SEQ ID NO: 16). Expression of the fusion protein of this protein and GFP was observed in the whole cell (Example 4).
【００３５】クロ−ン（Ｈ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、ＥＳＴの中に、９
０％以上の相同性を有するもの（例えば、アクセション
番号ＡＩ８７９１０５）が登録されていたが、部分配列
なのでクロ−ン（Ｈ）がコ−ドする蛋白質と同じ蛋白質
をコードしているかどうかは判定できない。 （Ｉ） ＨＰ１０５６９ ヒト類表皮癌細胞株ＫＢｃＤＮＡライブラリーから得ら
れたクローンＨＰ１０５６９のｃＤＮＡインサートの全
塩基配列を決定したところ、２６ｂｐの５’非翻訳領
域、２１３ｂｐのＯＲＦ、４０ｂｐの３’非翻訳領域か
らなる構造を有していた（配列番号１７）。ＯＲＦは７
０アミノ酸残基（配列番号１８）からなる蛋白質をコー
ドしており、インビトロ翻訳の結果、ＯＲＦから予想さ
れる分子量８，６９１とほぼ同じ９ｋＤａの翻訳産物が
生成した（実施例２）。この蛋白質とＧＦＰとの融合蛋
白質は、細胞全体に発現が認められた（実施例４）。When GenBank was searched using the nucleotide sequence of the clone (H) cDNA, 9% was found in the EST.
A protein having a homology of 0% or more (eg, Accession No. AI879105) was registered. However, since it is a partial sequence, it is determined whether clone (H) encodes the same protein as the protein encoded. Can not. (I) HP10569 The entire nucleotide sequence of the cDNA insert of clone HP10569 obtained from the human epidermoid carcinoma cell line KB cDNA library was determined. (SEQ ID NO: 17). ORF is 7
It encodes a protein consisting of 0 amino acid residues (SEQ ID NO: 18), and as a result of in vitro translation, a translation product of 9 kDa was generated, which is almost the same as the molecular weight of 8,691 predicted from ORF (Example 2). Expression of the fusion protein of this protein and GFP was observed in the whole cell (Example 4).
【００３６】クロ−ン（Ｉ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、ＥＳＴの中に、９
０％以上の相同性を有するもの（例えば、アクセション
番号ＡＩ３７６８４１）が登録されていたが、部分配列
なのでクロ−ン（Ｉ）がコ−ドする蛋白質と同じ蛋白質
をコードしているかどうかは判定できない。 （Ｊ） ＨＰ１０６０１ ヒトフィブロサルコ−マ細胞株ＨＴ−１０８０ｃＤＮＡ
ライブラリーから得られたクローンＨＰ１０６０１のｃ
ＤＮＡインサートの全塩基配列を決定したところ、９０
ｂｐの５’非翻訳領域、２０８８ｂｐのＯＲＦ、１１８
９ｂｐの３’非翻訳領域からなる構造を有していた（配
列番号１９）。ＯＲＦは６９５アミノ酸残基（配列番号
２０）からなる蛋白質をコードしており、インビトロ翻
訳の結果、ＯＲＦから予想される分子量７６，１０５よ
り大きい８１ｋＤａの翻訳産物が生成した（実施例
２）。この蛋白質とＧＦＰとの融合蛋白質は、核あるい
は粒子状の発現が認められた（実施例４）。When GenBank was searched using the nucleotide sequence of clone (I) cDNA, 9% was found in EST.
A protein having a homology of 0% or more (for example, Accession No. AI376841) was registered, but since it is a partial sequence, it is determined whether clone (I) encodes the same protein as the protein encoded. Can not. (J) HP10601 human fibrosarcoma cell line HT-1080 cDNA
C of clone HP10601 obtained from library
When the total base sequence of the DNA insert was determined, 90
5 bp untranslated region, 2088 bp ORF, 118
It had a structure consisting of a 9 bp 3 ′ untranslated region (SEQ ID NO: 19). The ORF encodes a protein consisting of 695 amino acid residues (SEQ ID NO: 20), and as a result of in vitro translation, a translation product of 81 kDa larger than the molecular weight of 76,105 predicted from the ORF was generated (Example 2). As for the fusion protein of this protein and GFP, nuclear or particulate expression was observed (Example 4).
【００３７】クロ−ン（Ｊ）ｃＤＮＡの塩基配列を用い
てＧｅｎＢａｎｋを検索したところ、ＥＳＴの中に、９
０％以上の相同性を有するもの（例えば、アクセション
番号Ｒ９７１２２）が登録されていたが、部分配列なの
でクロ−ン（Ｊ）がコ−ドする蛋白質と同じ蛋白質をコ
ードしているかどうかは判定できない。 実施例２：インビトロ翻訳による蛋白質合成 実施例１で単離したｃＤＮＡを有するプラスミドベクタ
ーを用いて、ＴNＴウサギ網状赤血球溶解物キット（プ
ロメガ社製）によるインビトロ転写／翻訳を行なった。
この際［35Ｓ］メチオニンを添加し、発現産物をラジオ
アイソトープでラベルした。いずれの反応もキットに付
属のプロトコールに従って行なった。When GenBank was searched using the nucleotide sequence of the clone (J) cDNA, 9% was found in the EST.
A protein having a homology of 0% or more (eg, Accession No. R97122) was registered, but since it is a partial sequence, it is determined whether clone (J) encodes the same protein as the protein encoded. Can not. Example 2: Protein Synthesis Example 1 by in vitro translation using a plasmid vector having the isolated cDNA, was subjected to in vitro transcription / translation by T N T rabbit reticulocyte lysate kit (Promega).
At this time, [ 35 S] methionine was added, and the expression product was labeled with a radioisotope. All reactions were performed according to the protocol attached to the kit.
【００３８】具体的な方法は次のとおりである。プラス
ミド２μｇを、ＴNＴウサギ網状赤血球溶解物１２．５
μｌ、緩衝液（キットに付属）０．５μｌ、アミノ酸混
合液（メチオニンを含まない）２μｌ、［35Ｓ］メチオ
ニン（アマーシャム社）２μｌ（０．３７ＭＢｑ／μ
ｌ）、Ｔ７ＲＮＡポリメラーゼ０．５μｌ、ＲＮａｓｉ
ｎ２０Ｕを含む総量２５μｌの反応液中で３０℃、９０
分間反応させた。反応液３μｌにＳＤＳサンプリングバ
ッファー（１２５ｍＭトリス塩酸緩衝液、ｐＨ６．８、
１２０ｍＭ２−メルカプトエタノール、２％ＳＤＳ溶
液、０．０２５％ブロモフェノールブルー、２０％グリ
セロール）２μｌを加え、９５℃３分間加熱処理した
後、ＳＤＳ−ポリアクリルアミドゲル電気泳動にかけ
た。オートラジオグラフィーを行ない、翻訳産物の分子
量を求めた。 実施例３：ＣＯＳ７細胞による発現 実施例１で単離したｃＤＮＡを保有する発現ベクターに
よって形質転換した大腸菌を１００μｇ／ｍｌアンピシ
リン含有２ｘＹＴ培地２ｍｌ中で３７℃２時間培養した
後、ヘルパーファージＭ１３ＫＯ７（５０μｌ）を添加
し、３７℃で一晩培養した。遠心によって分離した上澄
からポリエチレングリコール沈殿によって一本鎖ファー
ジ粒子を得た。これを１００μｌの１ｍＭトリス−０．
１ｍＭＥＤＴＡ、ｐＨ８（ＴＥ）に懸濁した。The specific method is as follows. Plasmid 2μg, T N T rabbit reticulocyte lysate 12.5
μl, buffer (included in the kit) 0.5 μl, amino acid mixture (without methionine) 2 μl, [ 35 S] methionine (Amersham) 2 μl (0.37 MBq / μm
l), 0.5 μl of T7 RNA polymerase, RNasi
n ° C at 90 ° C in a total volume of 25 μl
Allowed to react for minutes. To 3 μl of the reaction solution, add SDS sampling buffer (125 mM Tris-HCl buffer, pH 6.8,
2 μl of 120 mM 2-mercaptoethanol, 2% SDS solution, 0.025% bromophenol blue, 20% glycerol) was added, and the mixture was heated at 95 ° C. for 3 minutes, and then subjected to SDS-polyacrylamide gel electrophoresis. Autoradiography was performed to determine the molecular weight of the translation product. Example 3 Expression in COS7 Cells Escherichia coli transformed with the expression vector carrying the cDNA isolated in Example 1 was cultured in 2 ml of 2 × YT medium containing 100 μg / ml ampicillin at 37 ° C. for 2 hours, followed by helper phage M13KO7 (50 μl). ) Was added and the cells were cultured at 37 ° C. overnight. Single-stranded phage particles were obtained from the supernatant separated by centrifugation by polyethylene glycol precipitation. This was added to 100 μl of 1 mM Tris-0.
The cells were suspended in 1 mM EDTA, pH 8 (TE).
【００３９】サル腎臓由来培養細胞ＣＯＳ７は、１０％
ウシ胎児血清を含むダルベッコ改変イーグル（ＤＭＥ
Ｍ）培地中、５％ＣＯ2存在下、３７℃で培養した。１
ｘ105個のＣＯＳ７細胞を６穴プレート（ヌンク社、穴
の直径３ｃｍ）に植え、５％ＣＯ 2存在下、３７℃で２
２時間培養した。培地除去後、リン酸緩衝液で細胞表面
を洗浄し、さらに５０ｍＭトリス塩酸（ｐＨ７．５）を
含むＤＭＥＭ（ＴＤＭＥＭ）で再度洗浄した。この細胞
に一本鎖ファージ懸濁液１μｌ、ＤＭＥＭ培地０．６ｍ
ｌ、ＴＲＡＮＳＦＥＣＴＡＭTM（ＩＢＦ社）３μｌを懸
濁したものを添加し、５％ＣＯ2存在下、３７℃で３時
間培養した。サンプル液を除去後、ＴＤＭＥＭで細胞表
面を洗浄し、１０％ウシ胎児血清含有ＤＭＥＭを１穴あ
たり２ｍｌ加え、５％ＣＯ2存在下、３７℃にて２日間
培養した。培地を［35Ｓ］システインあるいは［35Ｓ］
メチオニンを含む培地に交換した後、１時間培養した。
遠心分離によって、培地と細胞を分けたあと、細胞画分
の蛋白質をＳＤＳ−ＰＡＧＥにかけた。 実施例４：緑色蛍光蛋白質（ＧＦＰ）融合蛋白質の発現 ＥｃｏＲＩ認識部位を付加した翻訳開始コドンから始ま
る２６merのセンスプライマーとＢａｍＨＩ認識部位を
を付加した停止コドンまでを含む２６merのアンチセン
スプライマーを用い、目的蛋白質をコ−ドするｃＤＮＡ
を鋳型としてＰＣＲにより翻訳領域を増幅した。ＰＣＲ
産物をＥｃｏＲＩとＢａｍＨＩで消化し、ＧＦＰ融合蛋
白質発現用ベクタ−ｐＥＧＦＰ−Ｎ１（Clontec社製）
のＥｃｏＲＩ−ＢａｍＨＩ部位に挿入した。塩基配列を
確認した後、得られた融合遺伝子発現ベクタ−を実施例
３に記載の方法によりＣＯＳ７細胞にトランスフェクト
した。蛍光顕微鏡により緑色蛍光の分布を観察し、目的
蛋白質の局在部位を調べた。 実施例５：抗体の作製 ＥｃｏＲＩ認識部位を付加した翻訳開始コドンから始ま
る２６merのセンスプライマーとＳａｌＩ認識配列を付
加した停止コドンまでを含む２６merのアンチセンスプ
ライマーを用い、各ｃＤＮＡを鋳型としてＰＣＲにより
翻訳領域を増幅した。ＰＣＲ産物をＥｃｏＲＩとＳａｌ
Ｉで消化し、ｐＧＥＸ−５Ｘ−１(ファルマシア社製)の
ＥｃｏＲＩとＳａｌＩ部位に挿入した。塩基配列を確認
した後、宿主大腸菌ＪＭ１０９の形質転換を行った。Ｌ
Ｂ培地中で３７℃、５時間培養し、ＩＰＴＧを最終濃度
が０．４ｍＭになるように加え、さらに３７℃で４時間
培養した。菌体を遠心により分離し、溶解溶液（５０ｍ
Ｍ Ｔｒｉｓ−ＨＣｌ ｐＨ７．５、１ｍＭ ＥＤＴＡ、
０．２ｍＭＰＭＦ）に溶かし、一度−８０℃で凍結させ
融解させた後、超音波破砕を行った。１０,０００ｘｇ
で３０分遠心し、上清にグルタチオンセファロース４Ｂ
を加え、４℃で１時間インキュベートした。ビーズを十
分洗浄した後、溶出溶液（５０ｍＭ Ｔｒｉｓ−ＨＣｌ
ｐＨ７．５、５０ｍＭグルタチオン）で融合蛋白質を溶
出した。得られた融合蛋白質を抗原として家兔に常法に
より免疫を行い抗血清を得た。抗血清はまず、４０％飽
和硫安沈殿画分をＧＳＴアフィニティーカラムによりＧ
ＳＴ抗体を除いた。素通り画分をさらにＧＳＴ融合蛋白
質の抗原カラムにより精製した。Monkey kidney-derived cultured cell COS7 is 10%
Dulbecco's modified Eagle containing fetal bovine serum (DME
M) 5% CO in mediumTwoThe cells were cultured at 37 ° C in the presence. 1
x10FiveOf COS7 cells in a 6-well plate (Nunc, well
3cm in diameter) and 5% CO Two2 at 37 ° C in the presence
Incubated for 2 hours. After removing the medium, cell surface with phosphate buffer
Was washed, and 50 mM Tris-HCl (pH 7.5) was further added.
Washed again with DMEM containing (TDMEM). This cell
1 μl of single-stranded phage suspension, 0.6 m of DMEM medium
1, TRANSFECTAMTM(IBF) Suspend 3 μl
Add the cloudy one and add 5% COTwo3 hours at 37 ° C in the presence
Culture was performed between the two. After removing the sample solution, remove the cell surface with TDMEM.
Wash the surface, and add 1 hole with DMEM containing 10% fetal bovine serum.
Add 2ml or 5% COTwo2 days at 37 ° C in the presence
Cultured. Change the medium to [35[S] cysteine or [35S]
After changing to a medium containing methionine, the cells were cultured for 1 hour.
After separating the cells from the medium by centrifugation, the cell fraction
Was subjected to SDS-PAGE. Example 4 Expression of Green Fluorescent Protein (GFP) Fusion Protein Beginning with a translation initiation codon to which an EcoRI recognition site has been added.
26mer sense primer and BamHI recognition site
26mer antisense containing up to the stop codon
CDNA encoding target protein using primers
Was used as a template to amplify the translation region by PCR. PCR
The product is digested with EcoRI and BamHI, and the GFP fusion protein is digested.
White matter expression vector-pEGFP-N1 (Clontec)
At the EcoRI-BamHI site. Base sequence
After confirmation, the obtained fusion gene expression vector
3. Transfect COS7 cells by the method described in 3.
did. Observe the distribution of green fluorescence with a fluorescence microscope,
The localization site of the protein was examined. Example 5: Preparation of antibody Beginning with a translation initiation codon to which an EcoRI recognition site has been added.
With a 26-mer sense primer and SalI recognition sequence
26-mer antisense probe including the added stop codon
PCR using PCR with each cDNA as template
The translation region was amplified. PCR products were EcoRI and Sal
I and digested with pGEX-5X-1 (Pharmacia)
It was inserted into EcoRI and SalI sites. Confirm base sequence
After that, the host E. coli JM109 was transformed. L
Incubate at 37 ° C. for 5 hours in B medium, and make IPTG the final concentration.
To 0.4 mM, and further at 37 ° C. for 4 hours.
Cultured. The cells were separated by centrifugation and the lysis solution (50 m
M Tris-HCl pH 7.5, 1 mM EDTA,
0.2 mM PMF) and freeze at -80 ° C once.
After melting, sonication was performed. 10,000xg
Centrifugation for 30 minutes, and glutathione Sepharose 4B was added to the supernatant.
Was added and incubated at 4 ° C. for 1 hour. Ten beads
After washing for 5 minutes, the elution solution (50 mM Tris-HCl
Dissolve the fusion protein at pH 7.5, 50 mM glutathione)
Issued. The obtained fusion protein is used as an antigen for the rabbit
Immunization was further performed to obtain an antiserum. Antisera should first be 40% saturated
Ammonium sulfate precipitate fraction was separated by GST affinity column into G
The ST antibody was removed. GST fusion protein
Purified by quality antigen column.
【００４０】[0040]
【発明の効果】以上詳しく説明したとおり、この出願に
よって、新規な精製ヒト蛋白質、これらの蛋白質をコー
ドしているＤＮＡ断片、このＤＮＡ断片の発現ベクタ
ー、この発現ベクターによる形質転換細胞、およびこの
蛋白質に対する抗体が提供される。この出願によって提
供される蛋白質は、いずれも細胞内で機能している蛋白
質と考えられるため、細胞内タ−ゲット蛋白質として、
対応するレセプターやリガンドの検出、新しい低分子医
薬のスクリーニングなどに利用できる。またこの蛋白質
に対する抗体を作製するための抗原として用いることが
できる。この出願によって提供されるＤＮＡ断片は、遺
伝子診断用プローブや遺伝子治療用遺伝子源として用い
ることができる。また、このＤＮＡ断片を用いることに
より、この蛋白質を大量に発現することができる。これ
ら遺伝子を導入してこの蛋白質を発現させた細胞は、こ
の蛋白質の修飾型を得るのに利用できる。この出願によ
って提供される抗体は、この発明の蛋白質の検出、定
量、精製などに利用できる。As described above in detail, according to the present application, a novel purified human protein, a DNA fragment encoding these proteins, an expression vector of this DNA fragment, a cell transformed with this expression vector, and this protein Are provided. Since all of the proteins provided by this application are considered to be proteins functioning in cells, as intracellular target proteins,
It can be used for detection of corresponding receptors and ligands, screening of new small molecule drugs, and the like. In addition, it can be used as an antigen for preparing an antibody against this protein. The DNA fragment provided by this application can be used as a probe for gene diagnosis or a gene source for gene therapy. By using this DNA fragment, the protein can be expressed in a large amount. Cells into which these proteins have been expressed by introducing these genes can be used to obtain modified forms of the proteins. The antibody provided by this application can be used for detection, quantification, purification, etc. of the protein of the present invention.
【００４１】[0041]
【配列表】 SEQUENCE LISTING <110> Japan Science and Technology Corporation <120> Human Proteins and cDNAs thereof (8) <130> NP00037-YS <140> <141> <160> 20 <170> PatentIn Ver. 2.1 <210> 1 <211> 1354 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (133)..(870) <400> 1 acccctcccc ctccccgcgg taccttgcac ttttctccct ccctgccccc tctcgagtcc 60 accctccggg ccttctgccc ctgatcgctt ggttttcctt gcagtcgcct gctgctgtcg 120 tcgggaggaa ag atg aat ggg agg gct gat ttt cga gag ccg aat gca gag 171 Met Asn Gly Arg Ala Asp Phe Arg Glu Pro Asn Ala Glu 1 5 10 gtt cca aga cca att ccc cac ata ggg cct gat tac att cca aca gag 219 Val Pro Arg Pro Ile Pro His Ile Gly Pro Asp Tyr Ile Pro Thr Glu 15 20 25 gaa gaa agg aga gtc ttc gca gaa tgc aat gat gaa agc ttc tgg ttc 267 Glu Glu Arg Arg Val Phe Ala Glu Cys Asn Asp Glu Ser Phe Trp Phe 30 35 40 45 aga tct gtg cct ttg gct gca aca agt atg ttg att act caa gga tta 315 Arg Ser Val Pro Leu Ala Ala Thr Ser Met Leu Ile Thr Gln Gly Leu 50 55 60 att agt aaa gga ata ctt tca agt cat ccc aaa tat ggt tcc atc cct 363 Ile Ser Lys Gly Ile Leu Ser Ser His Pro Lys Tyr Gly Ser Ile Pro 65 70 75 aaa ctt ata ctt gct tgt atc atg gga tac ttt gct gga aaa ctt tct 411 Lys Leu Ile Leu Ala Cys Ile Met Gly Tyr Phe Ala Gly Lys Leu Ser 80 85 90 tat gtg aaa act tgc caa gag aaa ttc aag aaa ctt gaa aat tcc ccc 459 Tyr Val Lys Thr Cys Gln Glu Lys Phe Lys Lys Leu Glu Asn Ser Pro 95 100 105 ctt gga gaa gct tta cga tca gga caa gca cga cga tct tca cca cct 507 Leu Gly Glu Ala Leu Arg Ser Gly Gln Ala Arg Arg Ser Ser Pro Pro 110 115 120 125 ggg cac tat tat caa aag tca aaa tat gac tca agt gtg agt ggt caa 555 Gly His Tyr Tyr Gln Lys Ser Lys Tyr Asp Ser Ser Val Ser Gly Gln 130 135 140 tca tct ttt gtg aca tcc cca gca gca gac aac ata gaa atg ctt cct 603 Ser Ser Phe Val Thr Ser Pro Ala Ala Asp Asn Ile Glu Met Leu Pro 145 150 155 cat tat gag cca att cca ttc agt tct tct atg aat gaa tct gct ccc 651 His Tyr Glu Pro Ile Pro Phe Ser Ser Ser Met Asn Glu Ser Ala Pro 160 165 170 act ggt att act gat cat att gtc caa gga cct gat ccc aac ctt gaa 699 Thr Gly Ile Thr Asp His Ile Val Gln Gly Pro Asp Pro Asn Leu Glu 175 180 185 gaa agt cct aaa aga aaa aat att aca tat gag gaa tta agg aat aag 747 Glu Ser Pro Lys Arg Lys Asn Ile Thr Tyr Glu Glu Leu Arg Asn Lys 190 195 200 205 aac aga gag tca tat gaa gta tct tta aca caa aag act gac ccc tca 795 Asn Arg Glu Ser Tyr Glu Val Ser Leu Thr Gln Lys Thr Asp Pro Ser 210 215 220 gtc agg cct atg cat gaa aga gtg cca aaa aaa gaa gtc aaa gta aac 843 Val Arg Pro Met His Glu Arg Val Pro Lys Lys Glu Val Lys Val Asn 225 230 235 aag tat gga gat act tgg gat gag tga aaaattacat cattggacat 890 Lys Tyr Gly Asp Thr Trp Asp Glu 240 245 gaaggagttt caacatccag cttcatctag gtggtcatga ttacctgcat gctttgagct 950 cagcagcagt cttcataaac acatttaaaa caagatcctg ggtttttgtg gtttgacttc 1010 tatggtgttt taaaaaaaca cagattttta gtgttaatat tgtgtaaatg tactcacctt 1070 agggattcat ttgaatgatg gtattatacc atgattgtat acagtttgtg aaattgttgc 1130 aagggcaaag ataactctta aaaaaccgtc gagattacaa tgctctagaa tcagcatata 1190 agaaaataaa tgatatctgc atgttgaatt ggggtggatg gggggagcaa gcataatttt 1250 taagtgtgaa gctttgcatc aagaaattat taaaaagctt tttttctcca gtattttctg 1310 tattatctta atgtttatgg caaataaaat gtaaaggaac atgc 1354 <210> 2 <211> 245 <212> PRT <213> Homo sapiens <400> 2 Met Asn Gly Arg Ala Asp Phe Arg Glu Pro Asn Ala Glu Val Pro Arg 1 5 10 15 Pro Ile Pro His Ile Gly Pro Asp Tyr Ile Pro Thr Glu Glu Glu Arg 20 25 30 Arg Val Phe Ala Glu Cys Asn Asp Glu Ser Phe Trp Phe Arg Ser Val 35 40 45 Pro Leu Ala Ala Thr Ser Met Leu Ile Thr Gln Gly Leu Ile Ser Lys 50 55 60 Gly Ile Leu Ser Ser His Pro Lys Tyr Gly Ser Ile Pro Lys Leu Ile 65 70 75 80 Leu Ala Cys Ile Met Gly Tyr Phe Ala Gly Lys Leu Ser Tyr Val Lys 85 90 95 Thr Cys Gln Glu Lys Phe Lys Lys Leu Glu Asn Ser Pro Leu Gly Glu 100 105 110 Ala Leu Arg Ser Gly Gln Ala Arg Arg Ser Ser Pro Pro Gly His Tyr 115 120 125 Tyr Gln Lys Ser Lys Tyr Asp Ser Ser Val Ser Gly Gln Ser Ser Phe 130 135 140 Val Thr Ser Pro Ala Ala Asp Asn Ile Glu Met Leu Pro His Tyr Glu 145 150 155 160 Pro Ile Pro Phe Ser Ser Ser Met Asn Glu Ser Ala Pro Thr Gly Ile 165 170 175 Thr Asp His Ile Val Gln Gly Pro Asp Pro Asn Leu Glu Glu Ser Pro 180 185 190 Lys Arg Lys Asn Ile Thr Tyr Glu Glu Leu Arg Asn Lys Asn Arg Glu 195 200 205 Ser Tyr Glu Val Ser Leu Thr Gln Lys Thr Asp Pro Ser Val Arg Pro 210 215 220 Met His Glu Arg Val Pro Lys Lys Glu Val Lys Val Asn Lys Tyr Gly 225 230 235 240 Asp Thr Trp Asp Glu 245 <210> 3 <211> 653 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (170)..(502) <400> 3 cagaagaggt agggcgccgc cgtgacagat tagtcctaaa gggaacgggg ttgttagttc 60 aattggctac cggaaaaaac caggctgggc tgggcgccgc catgacaacc gataccggaa 120 aaggcgggtc gttccccccg gacagcccta cgccggcaaa ggtctcgag atg cag gcg 178 Met Gln Ala 1 gcc cta gag gtc acc gct cgc tac tgt ggc cgg gag ctg gag cag tat 226 Ala Leu Glu Val Thr Ala Arg Tyr Cys Gly Arg Glu Leu Glu Gln Tyr 5 10 15 ggc cag tgt gtg gcg gcc aag ccg gaa tcc tgg cag cgg gac tgt cac 274 Gly Gln Cys Val Ala Ala Lys Pro Glu Ser Trp Gln Arg Asp Cys His 20 25 30 35 tac ctt aag atg agc att gcc cag tgc aca tcc tcc cac cca atc atc 322 Tyr Leu Lys Met Ser Ile Ala Gln Cys Thr Ser Ser His Pro Ile Ile 40 45 50 cgc cag atc cgc cag gcc tgt gct cag cct ttt gag gcc ttc gag gag 370 Arg Gln Ile Arg Gln Ala Cys Ala Gln Pro Phe Glu Ala Phe Glu Glu 55 60 65 tgt ctt cga cag aac gag gca gct gtg ggc aac tgt gca gag cat atg 418 Cys Leu Arg Gln Asn Glu Ala Ala Val Gly Asn Cys Ala Glu His Met 70 75 80 cgc cgc ttc ctg cag tgc gct gag cag gtg cag ccg cca cgc tca cct 466 Arg Arg Phe Leu Gln Cys Ala Glu Gln Val Gln Pro Pro Arg Ser Pro 85 90 95 gca act gtg gag gca cag cca ctt cct gcc tcc tga ggactcctct 512 Ala Thr Val Glu Ala Gln Pro Leu Pro Ala Ser 100 105 110 gacggcagga aaactggaca tgaatgactg cccccccgcc cctcccctgc agagtggcca 572 gatggagtcc tgagccctgg acatgggccc ggctttcctg gatatcagga cttccaataa 632 ataaagactc tgtatactgg g 653 <210> 4 <211> 110 <212> PRT <213> Homo sapiens <400> 4 Met Gln Ala Ala Leu Glu Val Thr Ala Arg Tyr Cys Gly Arg Glu Leu 1 5 10 15 Glu Gln Tyr Gly Gln Cys Val Ala Ala Lys Pro Glu Ser Trp Gln Arg 20 25 30 Asp Cys His Tyr Leu Lys Met Ser Ile Ala Gln Cys Thr Ser Ser His 35 40 45 Pro Ile Ile Arg Gln Ile Arg Gln Ala Cys Ala Gln Pro Phe Glu Ala 50 55 60 Phe Glu Glu Cys Leu Arg Gln Asn Glu Ala Ala Val Gly Asn Cys Ala 65 70 75 80 Glu His Met Arg Arg Phe Leu Gln Cys Ala Glu Gln Val Gln Pro Pro 85 90 95 Arg Ser Pro Ala Thr Val Glu Ala Gln Pro Leu Pro Ala Ser 100 105 110 <210> 5 <211> 643 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (40)..(411) <400> 5 gcggaagtac ggaccgtgaa ctggagtgga atcgcgact atg gga gct ccg ggg 54 Met Gly Ala Pro Gly 1 5 gga aag atc aac cgg ccc cga acg gag ctg aag aag aag ctg ttc aaa 102 Gly Lys Ile Asn Arg Pro Arg Thr Glu Leu Lys Lys Lys Leu Phe Lys 10 15 20 cgc cgg cgg gtg ttg aat cgg gag cgg cgt ctg agg cac cgg gtg gtc 150 Arg Arg Arg Val Leu Asn Arg Glu Arg Arg Leu Arg His Arg Val Val 25 30 35 ggg gct gtg ata gac caa ggg ctg atc acg cgg cac cac ctc aag aag 198 Gly Ala Val Ile Asp Gln Gly Leu Ile Thr Arg His His Leu Lys Lys 40 45 50 cgg gcg tcc agt gca cgt gcc aac att aca ctg tca ggg aag aag cgc 246 Arg Ala Ser Ser Ala Arg Ala Asn Ile Thr Leu Ser Gly Lys Lys Arg 55 60 65 aga aaa ctc ctc cag cag atc cgg ctt gcc cag aaa gag aag aca gcc 294 Arg Lys Leu Leu Gln Gln Ile Arg Leu Ala Gln Lys Glu Lys Thr Ala 70 75 80 85 atg gaa gtg gaa gcc cct tca aag cca gcc agg act agt gaa cca cag 342 Met Glu Val Glu Ala Pro Ser Lys Pro Ala Arg Thr Ser Glu Pro Gln 90 95 100 ctc aaa agg caa aag aag aca aaa gcc ccc cag gat gta gaa atg aag 390 Leu Lys Arg Gln Lys Lys Thr Lys Ala Pro Gln Asp Val Glu Met Lys 105 110 115 gac ctt gaa gat gag agc taa acctcttcca ctagaagatt ctcaactgga 441 Asp Leu Glu Asp Glu Ser 120 gccagccttc agactcagtg gttgtttcag aggactttga caaaagcaag gccccttttc 501 actctccaga tttcctccta cctaatggcc tactgacctc ccctagaggg atgtctttgg 561 gagggaagaa ggtacagaag aaagattgga gaagggtctc tctagcagtc aactccattt 621 gtaataaagc cctagcactc tg 643 <210> 6 <211> 123 <212> PRT <213> Homo sapiens <400> 6 Met Gly Ala Pro Gly Gly Lys Ile Asn Arg Pro Arg Thr Glu Leu Lys 1 5 10 15 Lys Lys Leu Phe Lys Arg Arg Arg Val Leu Asn Arg Glu Arg Arg Leu 20 25 30 Arg His Arg Val Val Gly Ala Val Ile Asp Gln Gly Leu Ile Thr Arg 35 40 45 His His Leu Lys Lys Arg Ala Ser Ser Ala Arg Ala Asn Ile Thr Leu 50 55 60 Ser Gly Lys Lys Arg Arg Lys Leu Leu Gln Gln Ile Arg Leu Ala Gln 65 70 75 80 Lys Glu Lys Thr Ala Met Glu Val Glu Ala Pro Ser Lys Pro Ala Arg 85 90 95 Thr Ser Glu Pro Gln Leu Lys Arg Gln Lys Lys Thr Lys Ala Pro Gln 100 105 110 Asp Val Glu Met Lys Asp Leu Glu Asp Glu Ser 115 120 <210> 7 <211> 1293 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (306)..(1019) <400> 7 gttaggctga gcctcttgct tgctgtgact ggtggagctg ccgcgctgtc cgcgttatct 60 cctcccggtg agaacgaacc gcagtgtcca ccggcgagga gccagccctg tcccggtcag 120 agaaagacga cgaggatacc tgggagcggg cggcggccgg gctgggccgc gccggtgcgg 180 gctggcgact ctgctcctcc gcttgctgct gtctctggga actgggtgcc agcgctgagg 240 ggcttccagc ggacagggac ccccttcccc ggctcccctg cccaccctgc cggggagggc 300 ggaag atg ccg gtg aag aag aag aga aaa tcc cct ggg gtg gca gca gca 350 Met Pro Val Lys Lys Lys Arg Lys Ser Pro Gly Val Ala Ala Ala 1 5 10 15 gta gcg gaa gac gga ggc ctc aaa aag tgt aaa atc tcc agc tat tgc 398 Val Ala Glu Asp Gly Gly Leu Lys Lys Cys Lys Ile Ser Ser Tyr Cys 20 25 30 aga tcc caa ccc cct gct aga cta ata agt gga gag gaa cat ttt tca 446 Arg Ser Gln Pro Pro Ala Arg Leu Ile Ser Gly Glu Glu His Phe Ser 35 40 45 agc aag aag tgc ctg gct tgg ttt tat gaa tat gca ggt cct gat gaa 494 Ser Lys Lys Cys Leu Ala Trp Phe Tyr Glu Tyr Ala Gly Pro Asp Glu 50 55 60 gtt gta ggg cca gaa gga atg gaa aaa ttt tgt gaa gac att ggt gtt 542 Val Val Gly Pro Glu Gly Met Glu Lys Phe Cys Glu Asp Ile Gly Val 65 70 75 gaa cct gaa aat att att atg tta gtt tta gcg tgg aaa ttg gag gct 590 Glu Pro Glu Asn Ile Ile Met Leu Val Leu Ala Trp Lys Leu Glu Ala 80 85 90 95 gaa agc atg gga ttt ttt acc aag gaa gaa tgg tta aag gga atg act 638 Glu Ser Met Gly Phe Phe Thr Lys Glu Glu Trp Leu Lys Gly Met Thr 100 105 110 tca tta cag tgt gac tgc aca gaa aag tta caa aac aaa ttt gac ttt 686 Ser Leu Gln Cys Asp Cys Thr Glu Lys Leu Gln Asn Lys Phe Asp Phe 115 120 125 ttg cgc tca cag ttg aat gat att tcg tca ttt aag aat atc tac aga 734 Leu Arg Ser Gln Leu Asn Asp Ile Ser Ser Phe Lys Asn Ile Tyr Arg 130 135 140 tat gcc ttt gat ttt gca agg gat aaa gat cag aga agc ctt gat att 782 Tyr Ala Phe Asp Phe Ala Arg Asp Lys Asp Gln Arg Ser Leu Asp Ile 145 150 155 gat act gct aaa tct atg tta gct ctt ctg ctt ggg agg aca tgg cca 830 Asp Thr Ala Lys Ser Met Leu Ala Leu Leu Leu Gly Arg Thr Trp Pro 160 165 170 175 ctg ttt tca gta ttt tac cag tac ctg gag caa tca aag tat cgt gtt 878 Leu Phe Ser Val Phe Tyr Gln Tyr Leu Glu Gln Ser Lys Tyr Arg Val 180 185 190 atg aac aaa gat caa tgg tac aat gta tta gaa ttc agc aga aca gtc 926 Met Asn Lys Asp Gln Trp Tyr Asn Val Leu Glu Phe Ser Arg Thr Val 195 200 205 cat gct gat ctt agt aac tat gat gaa gat ggt gct tgg cct gtt ctt 974 His Ala Asp Leu Ser Asn Tyr Asp Glu Asp Gly Ala Trp Pro Val Leu 210 215 220 ctt gat gaa ttt gtt gag tgg caa aaa gtc cgt cag aca tca tag 1019 Leu Asp Glu Phe Val Glu Trp Gln Lys Val Arg Gln Thr Ser 225 230 235 caagaactat gtgaagaaaa tgcaaacctt tcaattccca cgtgtataca agctaatgtg 1079 atgaggggga aaaaaatcca acgggtgcat tttcattcat atgaaagact tctcatagta 1139 cttttttttc ctttttttaa aggaggtttt tcttgttaca tgtgatgggc attgagccac 1199 acctcttctt agactgaata ttgaagtttt tgttttgagt tatgtttata acatttattt 1259 cagaacaata aagattcaga tttgtgacaa aggc 1293 <210> 8 <211> 237 <212> PRT <213> Homo sapiens <400> 8 Met Pro Val Lys Lys Lys Arg Lys Ser Pro Gly Val Ala Ala Ala Val 1 5 10 15 Ala Glu Asp Gly Gly Leu Lys Lys Cys Lys Ile Ser Ser Tyr Cys Arg 20 25 30 Ser Gln Pro Pro Ala Arg Leu Ile Ser Gly Glu Glu His Phe Ser Ser 35 40 45 Lys Lys Cys Leu Ala Trp Phe Tyr Glu Tyr Ala Gly Pro Asp Glu Val 50 55 60 Val Gly Pro Glu Gly Met Glu Lys Phe Cys Glu Asp Ile Gly Val Glu 65 70 75 80 Pro Glu Asn Ile Ile Met Leu Val Leu Ala Trp Lys Leu Glu Ala Glu 85 90 95 Ser Met Gly Phe Phe Thr Lys Glu Glu Trp Leu Lys Gly Met Thr Ser 100 105 110 Leu Gln Cys Asp Cys Thr Glu Lys Leu Gln Asn Lys Phe Asp Phe Leu 115 120 125 Arg Ser Gln Leu Asn Asp Ile Ser Ser Phe Lys Asn Ile Tyr Arg Tyr 130 135 140 Ala Phe Asp Phe Ala Arg Asp Lys Asp Gln Arg Ser Leu Asp Ile Asp 145 150 155 160 Thr Ala Lys Ser Met Leu Ala Leu Leu Leu Gly Arg Thr Trp Pro Leu 165 170 175 Phe Ser Val Phe Tyr Gln Tyr Leu Glu Gln Ser Lys Tyr Arg Val Met 180 185 190 Asn Lys Asp Gln Trp Tyr Asn Val Leu Glu Phe Ser Arg Thr Val His 195 200 205 Ala Asp Leu Ser Asn Tyr Asp Glu Asp Gly Ala Trp Pro Val Leu Leu 210 215 220 Asp Glu Phe Val Glu Trp Gln Lys Val Arg Gln Thr Ser 225 230 235 <210> 9 <211> 916 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (148)..(471) <400> 9 ctctctcggt ttgtctgggt catcttgtct gcccgccgct ggcctggccc cgtctgtctc 60 tctcagcagc tgtctttctc gcgcccactg gccggtctct cctcttcccc gcagttgcct 120 ccttctctgc ctgcctgggt ggccgcc atg ggc cgg aag cgg ctc atc act gat 174 Met Gly Arg Lys Arg Leu Ile Thr Asp 1 5 tcc tac ccg gtt gtg aag agg agg gag ggg ccc gct ggg cac agc aag 222 Ser Tyr Pro Val Val Lys Arg Arg Glu Gly Pro Ala Gly His Ser Lys 10 15 20 25 ggg gag ctg gca ccc gag cta ggg gag gag ccc cag ccc cgc gac gag 270 Gly Glu Leu Ala Pro Glu Leu Gly Glu Glu Pro Gln Pro Arg Asp Glu 30 35 40 gag gaa gcg gag ctg gag ctg ctg agg cag ttt gac ctg gcc tgg cag 318 Glu Glu Ala Glu Leu Glu Leu Leu Arg Gln Phe Asp Leu Ala Trp Gln 45 50 55 tac ggg ccc tgc acc ggg atc aca cgg ctg cag cgc tgg tgt cgg gcc 366 Tyr Gly Pro Cys Thr Gly Ile Thr Arg Leu Gln Arg Trp Cys Arg Ala 60 65 70 aag cag atg ggc ttg gag cct ccc cca gag gtg tgg cag gtg ctg aag 414 Lys Gln Met Gly Leu Glu Pro Pro Pro Glu Val Trp Gln Val Leu Lys 75 80 85 acc cac ccc gga gac ccc cgc ttc cag tgc agt ctc tgg cat ctc tat 462 Thr His Pro Gly Asp Pro Arg Phe Gln Cys Ser Leu Trp His Leu Tyr 90 95 100 105 ccc cta tga ggcaccacgt aagacctcct gcccttagct ctcttgctca 511 Pro Leu ccacccaaga acctcaggac agaagcgaga gcccattgct cctgctcagc tcagcccggc 571 tgcggaggaa cccttggcag gcagaacctg gaggtgtcag aggctcaact cctccatcta 631 accagcaggc tcccagagtc cccggaagag cctgcgcagc tgaagcagag tgcttctaga 691 tggagagtgg tcactgggga aaaggacctg gccatcacct tccaatacct gctgcctgtc 751 tccctgaccc atgatctggc aagttaggca cagtcagaca tggacagttg atccatgagg 811 aaaagatgct ctcccaccta aggccaggaa tctgagagca ggactggctg agctcccagg 871 gcaaggggtt cactaatgct tatcaataaa gaatattgag cctgg 916 <210> 10 <211> 107 <212> PRT <213> Homo sapiens <400> 10 Met Gly Arg Lys Arg Leu Ile Thr Asp Ser Tyr Pro Val Val Lys Arg 1 5 10 15 Arg Glu Gly Pro Ala Gly His Ser Lys Gly Glu Leu Ala Pro Glu Leu 20 25 30 Gly Glu Glu Pro Gln Pro Arg Asp Glu Glu Glu Ala Glu Leu Glu Leu 35 40 45 Leu Arg Gln Phe Asp Leu Ala Trp Gln Tyr Gly Pro Cys Thr Gly Ile 50 55 60 Thr Arg Leu Gln Arg Trp Cys Arg Ala Lys Gln Met Gly Leu Glu Pro 65 70 75 80 Pro Pro Glu Val Trp Gln Val Leu Lys Thr His Pro Gly Asp Pro Arg 85 90 95 Phe Gln Cys Ser Leu Trp His Leu Tyr Pro Leu 100 105 <210> 11 <211> 1002 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (51)..(731) <400> 11 ctattttctc acctggttcc cgcggcgagc cagcggcagc ggcggcggcg atg aga 56 Met Arg 1 cag aag cac tac ctt gag gct gca gcg cgg gga ctg cac gac agc tgc 104 Gln Lys His Tyr Leu Glu Ala Ala Ala Arg Gly Leu His Asp Ser Cys 5 10 15 ccg ggc caa gcc cgc tac ctc ctt ctc ttt ctc ttt tac agc tgg gcc 152 Pro Gly Gln Ala Arg Tyr Leu Leu Leu Phe Leu Phe Tyr Ser Trp Ala 20 25 30 tac act tcg tcg cac gat gat aag agc act ttt gaa gaa acg tgt cca 200 Tyr Thr Ser Ser His Asp Asp Lys Ser Thr Phe Glu Glu Thr Cys Pro 35 40 45 50 tac tgt ttc cag ctg ttg gtt ctg gat aac tct cga gtg cgt ctc aaa 248 Tyr Cys Phe Gln Leu Leu Val Leu Asp Asn Ser Arg Val Arg Leu Lys 55 60 65 ccc aaa gcc agg ttg aca ccc aaa ata cag aaa ctt ctt aat cga gaa 296 Pro Lys Ala Arg Leu Thr Pro Lys Ile Gln Lys Leu Leu Asn Arg Glu 70 75 80 gcg aga aac tat aca ctc agt ttt aaa gaa gca aaa atg gtg aaa aag 344 Ala Arg Asn Tyr Thr Leu Ser Phe Lys Glu Ala Lys Met Val Lys Lys 85 90 95 ttc aaa gac tcc aaa agt gta ttg ttg atc act tgt aaa aca tgc aac 392 Phe Lys Asp Ser Lys Ser Val Leu Leu Ile Thr Cys Lys Thr Cys Asn 100 105 110 aga aca gtg aaa cat cat ggt aaa agt aga agc ttt gtg tca aca ttg 440 Arg Thr Val Lys His His Gly Lys Ser Arg Ser Phe Val Ser Thr Leu 115 120 125 130 aag agc aat cct gcc act cct aca agt aaa ctc agc ctg aag aca cca 488 Lys Ser Asn Pro Ala Thr Pro Thr Ser Lys Leu Ser Leu Lys Thr Pro 135 140 145 gag aga agg act gca aac cca aat cat gac atg tct ggc tcg aaa ggc 536 Glu Arg Arg Thr Ala Asn Pro Asn His Asp Met Ser Gly Ser Lys Gly 150 155 160 aag agc cca gca tcg gtt ttc aga aca cct aca tct gga cag tca gta 584 Lys Ser Pro Ala Ser Val Phe Arg Thr Pro Thr Ser Gly Gln Ser Val 165 170 175 tct act tgc tcc tca aag aac acc agc aaa aca aag aaa cac ttc tct 632 Ser Thr Cys Ser Ser Lys Asn Thr Ser Lys Thr Lys Lys His Phe Ser 180 185 190 caa cta aaa atg tta ctt agt cag aat gaa tcc caa aag att cca aag 680 Gln Leu Lys Met Leu Leu Ser Gln Asn Glu Ser Gln Lys Ile Pro Lys 195 200 205 210 gtg gac ttc aga aat ttc tta tct tct ctg aag ggt gga ctt tta aaa 728 Val Asp Phe Arg Asn Phe Leu Ser Ser Leu Lys Gly Gly Leu Leu Lys 215 220 225 taa gaaatgcctg atgtcaattc tgaaactaaa gttggtaaaa caacttttta 781 aactcttatt cattttttga atacatggaa actagatctg aatgcaaact tttcttggca 841 tccttcagtg tttatgggga aaatacctca ttagtgtgaa tacctgaaac ctgcctacct 901 cataggacag ctgtgaggat caaaaaatat atgaaagttc cttgtagata catatctata 961 gatatatatg tgtatgtata taaagataga tatatacatt g 1002 <210> 12 <211> 226 <212> PRT <213> Homo sapiens <400> 12 Met Arg Gln Lys His Tyr Leu Glu Ala Ala Ala Arg Gly Leu His Asp 1 5 10 15 Ser Cys Pro Gly Gln Ala Arg Tyr Leu Leu Leu Phe Leu Phe Tyr Ser 20 25 30 Trp Ala Tyr Thr Ser Ser His Asp Asp Lys Ser Thr Phe Glu Glu Thr 35 40 45 Cys Pro Tyr Cys Phe Gln Leu Leu Val Leu Asp Asn Ser Arg Val Arg 50 55 60 Leu Lys Pro Lys Ala Arg Leu Thr Pro Lys Ile Gln Lys Leu Leu Asn 65 70 75 80 Arg Glu Ala Arg Asn Tyr Thr Leu Ser Phe Lys Glu Ala Lys Met Val 85 90 95 Lys Lys Phe Lys Asp Ser Lys Ser Val Leu Leu Ile Thr Cys Lys Thr 100 105 110 Cys Asn Arg Thr Val Lys His His Gly Lys Ser Arg Ser Phe Val Ser 115 120 125 Thr Leu Lys Ser Asn Pro Ala Thr Pro Thr Ser Lys Leu Ser Leu Lys 130 135 140 Thr Pro Glu Arg Arg Thr Ala Asn Pro Asn His Asp Met Ser Gly Ser 145 150 155 160 Lys Gly Lys Ser Pro Ala Ser Val Phe Arg Thr Pro Thr Ser Gly Gln 165 170 175 Ser Val Ser Thr Cys Ser Ser Lys Asn Thr Ser Lys Thr Lys Lys His 180 185 190 Phe Ser Gln Leu Lys Met Leu Leu Ser Gln Asn Glu Ser Gln Lys Ile 195 200 205 Pro Lys Val Asp Phe Arg Asn Phe Leu Ser Ser Leu Lys Gly Gly Leu 210 215 220 Leu Lys 225 <210> 13 <211> 1753 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (268)..(1455) <400> 13 gcctttgttt acaaccctgc catgatctcc ctcttgcaaa agcgagggct acagaacagg 60 cattcaggag tcctgtgctc cagtcacagc cttttctgtt cttcagctag gagacaccaa 120 accctcagga agatttacta tagctaagag aaaactgcag cagaaagggc gcggctacct 180 acttcttaaa ttccgtttgt ggaccctcag actcttagtc ccctactccc agatacagcg 240 gccctaccgt ggctcctggc aagaagc atg gat ctc gga atc cct gac ctg ctg 294 Met Asp Leu Gly Ile Pro Asp Leu Leu 1 5 gac gcg tgg ctg gag ccc cca gag gat atc ttc tcg aca gga tcc gtc 342 Asp Ala Trp Leu Glu Pro Pro Glu Asp Ile Phe Ser Thr Gly Ser Val 10 15 20 25 ctg gag ctg gga ctc cac tgc ccc cct cca gag gtt ccg gta act agg 390 Leu Glu Leu Gly Leu His Cys Pro Pro Pro Glu Val Pro Val Thr Arg 30 35 40 cta cag gaa cag gga ctg caa ggc tgg aag tcc ggt ggg gac cgt ggc 438 Leu Gln Glu Gln Gly Leu Gln Gly Trp Lys Ser Gly Gly Asp Arg Gly 45 50 55 tgt ggc ctt caa gag agt gag cct gaa gat ttc ttg aag ctt ttc att 486 Cys Gly Leu Gln Glu Ser Glu Pro Glu Asp Phe Leu Lys Leu Phe Ile 60 65 70 gat ccc aat gag gtg tac tgc tca gaa gca tct cct ggc agt gac agt 534 Asp Pro Asn Glu Val Tyr Cys Ser Glu Ala Ser Pro Gly Ser Asp Ser 75 80 85 ggc atc tct gag gac ccc tgc cat cca gac agt ccc cct gcc ccc agg 582 Gly Ile Ser Glu Asp Pro Cys His Pro Asp Ser Pro Pro Ala Pro Arg 90 95 100 105 gca acc agt tct cct atg ctc tat gag gtt gtc tat gag gca ggg gcc 630 Ala Thr Ser Ser Pro Met Leu Tyr Glu Val Val Tyr Glu Ala Gly Ala 110 115 120 ctg gag agg atg cag ggg gaa act ggg cca aat gta ggc ctt atc tcc 678 Leu Glu Arg Met Gln Gly Glu Thr Gly Pro Asn Val Gly Leu Ile Ser 125 130 135 atc cag cta gat cag tgg agc cca gca ttt atg gtg cct gat tcc tgc 726 Ile Gln Leu Asp Gln Trp Ser Pro Ala Phe Met Val Pro Asp Ser Cys 140 145 150 atg gtc agt gag ctg ccc ttt gat gct cat gcc cac atc ctg ccc aga 774 Met Val Ser Glu Leu Pro Phe Asp Ala His Ala His Ile Leu Pro Arg 155 160 165 gca ggc acc gta gcc cca gtg ccc tgt aca acc ctg ctg ccc tgt caa 822 Ala Gly Thr Val Ala Pro Val Pro Cys Thr Thr Leu Leu Pro Cys Gln 170 175 180 185 acc ctg ttc ctg acc gat gag gag aag cgt ctg ctg ggg cag gaa ggg 870 Thr Leu Phe Leu Thr Asp Glu Glu Lys Arg Leu Leu Gly Gln Glu Gly 190 195 200 gtt tcc ctg ccc tct cac ctg ccc ctc acc aag gca gag gag agg gtc 918 Val Ser Leu Pro Ser His Leu Pro Leu Thr Lys Ala Glu Glu Arg Val 205 210 215 ctc aag aag gtc agg agg aaa atc cgt aac aag cag tca gct cag gac 966 Leu Lys Lys Val Arg Arg Lys Ile Arg Asn Lys Gln Ser Ala Gln Asp 220 225 230 agt cgg cgg cgg aag aag gag tac att gat ggg ctg gag agc agg gtg 1014 Ser Arg Arg Arg Lys Lys Glu Tyr Ile Asp Gly Leu Glu Ser Arg Val 235 240 245 gca gcc tgt tct gca cag aac caa gaa tta cag aaa aaa gtc cag gag 1062 Ala Ala Cys Ser Ala Gln Asn Gln Glu Leu Gln Lys Lys Val Gln Glu 250 255 260 265 ctg gag agg cac aac atc tcc ttg gta gct cag ctc cgc cag ctg cag 1110 Leu Glu Arg His Asn Ile Ser Leu Val Ala Gln Leu Arg Gln Leu Gln 270 275 280 acg cta att gct caa act tcc aac aaa gct gcc cag acc agc act tgt 1158 Thr Leu Ile Ala Gln Thr Ser Asn Lys Ala Ala Gln Thr Ser Thr Cys 285 290 295 gtt ttg att ctt ctt ttt tcc ctg gct ctc atc atc ctg ccc agc ttc 1206 Val Leu Ile Leu Leu Phe Ser Leu Ala Leu Ile Ile Leu Pro Ser Phe 300 305 310 agt cca ttc cag agt cga cca gaa gct ggg tct gag gat tac cag cct 1254 Ser Pro Phe Gln Ser Arg Pro Glu Ala Gly Ser Glu Asp Tyr Gln Pro 315 320 325 cac gga gtg act tcc aga aat atc ctg acc cac aag gac gta aca gaa 1302 His Gly Val Thr Ser Arg Asn Ile Leu Thr His Lys Asp Val Thr Glu 330 335 340 345 aat ctg gag acc caa gtg gta gag tcc aga ctg agg gag cca cct gga 1350 Asn Leu Glu Thr Gln Val Val Glu Ser Arg Leu Arg Glu Pro Pro Gly 350 355 360 gcc aag gat gca aat ggc tca aca agg aca ctg ctt gag aag atg gga 1398 Ala Lys Asp Ala Asn Gly Ser Thr Arg Thr Leu Leu Glu Lys Met Gly 365 370 375 ggg aag cca aga ccc agt ggg cgc atc cgg tcc gtg ctg cat gca gat 1446 Gly Lys Pro Arg Pro Ser Gly Arg Ile Arg Ser Val Leu His Ala Asp 380 385 390 gag atg tga gctggaacag accttcctgg cccacttcct gatcacaagg 1495 Glu Met 395 aatcctgggc ttccttatgg ctttgcttcc cactgggatt cctacttagg tgtctgccct 1555 caggggtcca aatcacttca ggacacccca agagatgtcc tttagtctct gcctgaggcc 1615 tagtctgcat ttgtttgcat atatgagagg gtacctcaaa tacttctgtt atgtatctgt 1675 gattttattt cttctttggg tatagggttg aggggaaata agttttgagt gagaaataaa 1735 cgttttagct gaaattgt 1753 <210> 14 <211> 395 <212> PRT <213> Homo sapiens <400> 14 Met Asp Leu Gly Ile Pro Asp Leu Leu Asp Ala Trp Leu Glu Pro Pro 1 5 10 15 Glu Asp Ile Phe Ser Thr Gly Ser Val Leu Glu Leu Gly Leu His Cys 20 25 30 Pro Pro Pro Glu Val Pro Val Thr Arg Leu Gln Glu Gln Gly Leu Gln 35 40 45 Gly Trp Lys Ser Gly Gly Asp Arg Gly Cys Gly Leu Gln Glu Ser Glu 50 55 60 Pro Glu Asp Phe Leu Lys Leu Phe Ile Asp Pro Asn Glu Val Tyr Cys 65 70 75 80 Ser Glu Ala Ser Pro Gly Ser Asp Ser Gly Ile Ser Glu Asp Pro Cys 85 90 95 His Pro Asp Ser Pro Pro Ala Pro Arg Ala Thr Ser Ser Pro Met Leu 100 105 110 Tyr Glu Val Val Tyr Glu Ala Gly Ala Leu Glu Arg Met Gln Gly Glu 115 120 125 Thr Gly Pro Asn Val Gly Leu Ile Ser Ile Gln Leu Asp Gln Trp Ser 130 135 140 Pro Ala Phe Met Val Pro Asp Ser Cys Met Val Ser Glu Leu Pro Phe 145 150 155 160 Asp Ala His Ala His Ile Leu Pro Arg Ala Gly Thr Val Ala Pro Val 165 170 175 Pro Cys Thr Thr Leu Leu Pro Cys Gln Thr Leu Phe Leu Thr Asp Glu 180 185 190 Glu Lys Arg Leu Leu Gly Gln Glu Gly Val Ser Leu Pro Ser His Leu 195 200 205 Pro Leu Thr Lys Ala Glu Glu Arg Val Leu Lys Lys Val Arg Arg Lys 210 215 220 Ile Arg Asn Lys Gln Ser Ala Gln Asp Ser Arg Arg Arg Lys Lys Glu 225 230 235 240 Tyr Ile Asp Gly Leu Glu Ser Arg Val Ala Ala Cys Ser Ala Gln Asn 245 250 255 Gln Glu Leu Gln Lys Lys Val Gln Glu Leu Glu Arg His Asn Ile Ser 260 265 270 Leu Val Ala Gln Leu Arg Gln Leu Gln Thr Leu Ile Ala Gln Thr Ser 275 280 285 Asn Lys Ala Ala Gln Thr Ser Thr Cys Val Leu Ile Leu Leu Phe Ser 290 295 300 Leu Ala Leu Ile Ile Leu Pro Ser Phe Ser Pro Phe Gln Ser Arg Pro 305 310 315 320 Glu Ala Gly Ser Glu Asp Tyr Gln Pro His Gly Val Thr Ser Arg Asn 325 330 335 Ile Leu Thr His Lys Asp Val Thr Glu Asn Leu Glu Thr Gln Val Val 340 345 350 Glu Ser Arg Leu Arg Glu Pro Pro Gly Ala Lys Asp Ala Asn Gly Ser 355 360 365 Thr Arg Thr Leu Leu Glu Lys Met Gly Gly Lys Pro Arg Pro Ser Gly 370 375 380 Arg Ile Arg Ser Val Leu His Ala Asp Glu Met 385 390 395 <210> 15 <211> 668 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (54)..(122) <400> 15 ctttcttcct tttggtgcga gcttgctgtg gtttttgctc tgggtcctct ggg atg 56 Met 1 gcg cct ggc tgt ggc cgc gtg gtc tct cac gca ggg gcg ccg ggc ggg 104 Ala Pro Gly Cys Gly Arg Val Val Ser His Ala Gly Ala Pro Gly Gly 5 10 15 gga acg cgg cca ccc tga gtctggtgag tcgactgcgg cggcctgtgt 152 Gly Thr Arg Pro Pro 20 ccgaagtgtc cggggccgtg aacaagggca gcggcctggc ctcaggcctg cgttcccacg 212 tttggaaacg gggagcttcg tcgattttgt ttacatcatc gactatgcca gggagttctc 272 cagataagcc tggttttatt ttcgtcagtg aaaaggcctt accgtataac tgactttatg 332 cttgccctgc ccccgtataa aataacttaa aagcagcgtg cctggttaca gctgtttcca 392 cgtgcggtgc tcgtcgggag tgatcaccta ccctacaggt ggaagatgga tgcctgaagt 452 gtagactgct gctagctgaa taccatctgg gagcataaag gtgacctgaa ggatgtcctt 512 ggtgaggatt ttgaaaattt gatcttcaca agagttgcct ggatcatttg aaatttctgg 572 gagtctgagg agtactgaca taattacctg ctggagtctg taaatacaca tttaagacag 632 tgaggatgtg aataaatata ttaatgcaaa aaaaac 668 <210> 16 <211> 22 <212> PRT <213> Homo sapiens <400> 16 Met Ala Pro Gly Cys Gly Arg Val Val Ser His Ala Gly Ala Pro Gly 1 5 10 15 Gly Gly Thr Arg Pro Pro 20 <210> 17 <211> 279 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (27)..(239) <400> 17 atccctctcc acgacctcgg tcgagc atg ttc acc agg gcc cag gtg aga cgg 53 Met Phe Thr Arg Ala Gln Val Arg Arg 1 5 att ctg cag cgg gtg ccc ggg aag cag cga ttt ggc atc tac cgg ttc 101 Ile Leu Gln Arg Val Pro Gly Lys Gln Arg Phe Gly Ile Tyr Arg Phe 10 15 20 25 ctg ccc ttc ttt ttt gtc ctg gga gga acg atg gag tgg atc atg att 149 Leu Pro Phe Phe Phe Val Leu Gly Gly Thr Met Glu Trp Ile Met Ile 30 35 40 aaa gtg cgc gtg ggc cag gag acc ttc tat gat gtc tac cgt aga aaa 197 Lys Val Arg Val Gly Gln Glu Thr Phe Tyr Asp Val Tyr Arg Arg Lys 45 50 55 gcc tca gaa aga cag tat cag aga agg ctg gaa gat gaa tga 239 Ala Ser Glu Arg Gln Tyr Gln Arg Arg Leu Glu Asp Glu 60 65 70 gactgaactt cagcagtcaa taaagtcaat atgaattttt 279 <210> 18 <211> 70 <212> PRT <213> Homo sapiens <400> 18 Met Phe Thr Arg Ala Gln Val Arg Arg Ile Leu Gln Arg Val Pro Gly 1 5 10 15 Lys Gln Arg Phe Gly Ile Tyr Arg Phe Leu Pro Phe Phe Phe Val Leu 20 25 30 Gly Gly Thr Met Glu Trp Ile Met Ile Lys Val Arg Val Gly Gln Glu 35 40 45 Thr Phe Tyr Asp Val Tyr Arg Arg Lys Ala Ser Glu Arg Gln Tyr Gln 50 55 60 Arg Arg Leu Glu Asp Glu 65 70 <210> 19 <211> 3367 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (91)..(2178) <400> 19 cagatatact gagtgagccc tgagaagcag tctcagatcc tgacggtgca gcagcccgca 60 gcctcagcca gggagtccca gccgctttca atg gag gag aag ccc ggc cag cca 114 Met Glu Glu Lys Pro Gly Gln Pro 1 5 cag cct cag cac cat cac agc cac cac cat ccg cac cat cac cct cag 162 Gln Pro Gln His His His Ser His His His Pro His His His Pro Gln 10 15 20 cag cag cag cag cag ccg cac cac cac cac cat tat tat ttc tac aac 210 Gln Gln Gln Gln Gln Pro His His His His His Tyr Tyr Phe Tyr Asn 25 30 35 40 cac agc cac aac cac cac cac cac cat cat cac cag cag cct cac caa 258 His Ser His Asn His His His His His His His Gln Gln Pro His Gln 45 50 55 tac ctg cag cat gga gcc gag ggc agc ccc aag gcc cag cca aag ccg 306 Tyr Leu Gln His Gly Ala Glu Gly Ser Pro Lys Ala Gln Pro Lys Pro 60 65 70 ctg aaa cat gag cag aaa cac acc ctc cag cag cac cag gaa acg ccg 354 Leu Lys His Glu Gln Lys His Thr Leu Gln Gln His Gln Glu Thr Pro 75 80 85 aag aag aaa aca ggc tat ggt gaa cta aac ggt aat gct gga gaa aga 402 Lys Lys Lys Thr Gly Tyr Gly Glu Leu Asn Gly Asn Ala Gly Glu Arg 90 95 100 gaa ata tct tta aag aac ctg agt tct gat gaa gcc acc aac cct att 450 Glu Ile Ser Leu Lys Asn Leu Ser Ser Asp Glu Ala Thr Asn Pro Ile 105 110 115 120 tcc agg gtc ctc aat ggc aac cag caa gtt gta gac act agc ctg aag 498 Ser Arg Val Leu Asn Gly Asn Gln Gln Val Val Asp Thr Ser Leu Lys 125 130 135 cag act gta aag gcc aac acc ttt ggg aaa gca gga att aaa acc aag 546 Gln Thr Val Lys Ala Asn Thr Phe Gly Lys Ala Gly Ile Lys Thr Lys 140 145 150 aat ttc att cag aaa aac agt atg gac aaa aag aat ggg aag tct tat 594 Asn Phe Ile Gln Lys Asn Ser Met Asp Lys Lys Asn Gly Lys Ser Tyr 155 160 165 gaa aat aaa tct gga gag aat cag tct gta gat aag tct gat act ata 642 Glu Asn Lys Ser Gly Glu Asn Gln Ser Val Asp Lys Ser Asp Thr Ile 170 175 180 cca att cca aat ggt gtg gta aca aat aat tct ggt tat att act aat 690 Pro Ile Pro Asn Gly Val Val Thr Asn Asn Ser Gly Tyr Ile Thr Asn 185 190 195 200 ggt tat atg agt aaa gga gca gat aat gat ggt agt gga tct gag agc 738 Gly Tyr Met Ser Lys Gly Ala Asp Asn Asp Gly Ser Gly Ser Glu Ser 205 210 215 gga tat aca act cct aaa aaa agg aaa gct agg cgc aat agt gcc aag 786 Gly Tyr Thr Thr Pro Lys Lys Arg Lys Ala Arg Arg Asn Ser Ala Lys 220 225 230 ggt tgt gaa aac ctt aat ata gtg cag gac aaa ata atg caa caa gag 834 Gly Cys Glu Asn Leu Asn Ile Val Gln Asp Lys Ile Met Gln Gln Glu 235 240 245 acc agt gtc cca acc tta aaa cag gga ctt gaa act ttc aag cct gac 882 Thr Ser Val Pro Thr Leu Lys Gln Gly Leu Glu Thr Phe Lys Pro Asp 250 255 260 tat agt gaa caa aag gga aat cga gta gat ggt tcg aag ccc att tgg 930 Tyr Ser Glu Gln Lys Gly Asn Arg Val Asp Gly Ser Lys Pro Ile Trp 265 270 275 280 aag tat gaa act ggg cct gga gga aca agt cga gga aaa cct gct gtg 978 Lys Tyr Glu Thr Gly Pro Gly Gly Thr Ser Arg Gly Lys Pro Ala Val 285 290 295 ggt gat atg ctt cgg aaa agc tca gat agt aaa cct ggt gtg agc agc 1026 Gly Asp Met Leu Arg Lys Ser Ser Asp Ser Lys Pro Gly Val Ser Ser 300 305 310 aaa aag ttt gat gat cgg ccc aaa gga aag cat gct tca gct gtt gcc 1074 Lys Lys Phe Asp Asp Arg Pro Lys Gly Lys His Ala Ser Ala Val Ala 315 320 325 tcc aaa gag gac tcg tgg acc cta ttt aaa cca ccc cca gtt ttt cca 1122 Ser Lys Glu Asp Ser Trp Thr Leu Phe Lys Pro Pro Pro Val Phe Pro 330 335 340 gtg gac aat agc agt gct aaa ata gtt cct aaa ata agt tat gca agc 1170 Val Asp Asn Ser Ser Ala Lys Ile Val Pro Lys Ile Ser Tyr Ala Ser 345 350 355 360 aaa gtt aag gaa aac ctc aac aaa act ata cag aac tct tct gtg tca 1218 Lys Val Lys Glu Asn Leu Asn Lys Thr Ile Gln Asn Ser Ser Val Ser 365 370 375 cca act tca tct tca tca tct tca tca tct acc ggg gaa act cag acc 1266 Pro Thr Ser Ser Ser Ser Ser Ser Ser Ser Thr Gly Glu Thr Gln Thr 380 385 390 caa tca tca agt cgc tta tcc cag gtc cct atg tca gcg ctg aaa tct 1314 Gln Ser Ser Ser Arg Leu Ser Gln Val Pro Met Ser Ala Leu Lys Ser 395 400 405 gtt act tct gcc aac ttt tct aat ggg cct gtt tta gca ggg act gat 1362 Val Thr Ser Ala Asn Phe Ser Asn Gly Pro Val Leu Ala Gly Thr Asp 410 415 420 gga aat gtt tat cct cca ggg ggt cag cca ctg cta act act gct gct 1410 Gly Asn Val Tyr Pro Pro Gly Gly Gln Pro Leu Leu Thr Thr Ala Ala 425 430 435 440 aat act cta aca ccc atc tct tct ggg aca gat tca gtt ctc cag gac 1458 Asn Thr Leu Thr Pro Ile Ser Ser Gly Thr Asp Ser Val Leu Gln Asp 445 450 455 atg agt cta act tca gca gct gtt gaa caa att aag act agc ctt ttt 1506 Met Ser Leu Thr Ser Ala Ala Val Glu Gln Ile Lys Thr Ser Leu Phe 460 465 470 atc tat cct tca aat atg caa act atg ctg ttg agc aca gca caa gtg 1554 Ile Tyr Pro Ser Asn Met Gln Thr Met Leu Leu Ser Thr Ala Gln Val 475 480 485 gat ctg ccc tct cag aca gat cag caa aac ctg ggg gat atc ttc cag 1602 Asp Leu Pro Ser Gln Thr Asp Gln Gln Asn Leu Gly Asp Ile Phe Gln 490 495 500 aat cag tgg ggt tta tca ttt ata aat gag ccc agt gct ggc cct gag 1650 Asn Gln Trp Gly Leu Ser Phe Ile Asn Glu Pro Ser Ala Gly Pro Glu 505 510 515 520 act gtt act ggg aag tca tca gag cat aaa gtg atg gag gtg aca ttt 1698 Thr Val Thr Gly Lys Ser Ser Glu His Lys Val Met Glu Val Thr Phe 525 530 535 caa gga gaa tat cct gct act ttg gtt tca cag ggt gct gaa ata att 1746 Gln Gly Glu Tyr Pro Ala Thr Leu Val Ser Gln Gly Ala Glu Ile Ile 540 545 550 ccc tca gga act gag cat cct gtg ttt ccc aag gct tac gag ctg gag 1794 Pro Ser Gly Thr Glu His Pro Val Phe Pro Lys Ala Tyr Glu Leu Glu 555 560 565 aaa cgg act agt cct caa gtt ctg ggt agc att cta aaa tct ggg act 1842 Lys Arg Thr Ser Pro Gln Val Leu Gly Ser Ile Leu Lys Ser Gly Thr 570 575 580 act agt gag agt gga gcc tta tcc ttg gaa ccc agt cat ata ggt gac 1890 Thr Ser Glu Ser Gly Ala Leu Ser Leu Glu Pro Ser His Ile Gly Asp 585 590 595 600 ctg cag aaa gca gac acc agt agt caa ggt gct tta gtg ttt ctc tca 1938 Leu Gln Lys Ala Asp Thr Ser Ser Gln Gly Ala Leu Val Phe Leu Ser 605 610 615 aag gac tac gag ata gaa agt caa aat cct ctg gcc tct cct acg aac 1986 Lys Asp Tyr Glu Ile Glu Ser Gln Asn Pro Leu Ala Ser Pro Thr Asn 620 625 630 act ttg tta ggc tct gcc aaa gaa cag aga tac cag aga ggc cta gaa 2034 Thr Leu Leu Gly Ser Ala Lys Glu Gln Arg Tyr Gln Arg Gly Leu Glu 635 640 645 agg aat gat agc tgg ggt tct ttt gac ctg agg gct gct att gta tat 2082 Arg Asn Asp Ser Trp Gly Ser Phe Asp Leu Arg Ala Ala Ile Val Tyr 650 655 660 cac act aaa gaa atg gaa tct att tgg aat ttg cag aag caa gat ccc 2130 His Thr Lys Glu Met Glu Ser Ile Trp Asn Leu Gln Lys Gln Asp Pro 665 670 675 680 aaa agg ata atc act tac aat gaa gcc atg gat agt cca gat caa tga 2178 Lys Arg Ile Ile Thr Tyr Asn Glu Ala Met Asp Ser Pro Asp Gln 685 690 695 aggaccagac tgcctattcg taacctttct gcagcattag agccatcgtt catgggggac 2238 acaaggcttt tatgctccta gatcttcaac gcagcagagg aaccataagt agaatcacag 2298 gataatatat acaaatatat atatatacat atatatatat atagttattt aaaaaaggca 2358 actgaaagta attagacttc ttaaggaatc aaatttattt caagagacta cacatggtta 2418 tttaatctcc ggtactgaat aggttttttt tcttctgtta gtttttgttt ttaagtgtga 2478 atgcaagtga ttaatgaata cagacttaac aagtgtggtt ctaaagttcc tgctgtcatc 2538 aacttgggca acaaatgacc cactggaaag gcaaatccac ttaaaagatc tctgtatctt 2598 gttctgtgac tgaagtgata cactaatcac ggggaaccca gaatgattca acattttccc 2658 cccactcctc ccttgatctt tttggtttta ctttaattaa gccctgcgag aatgctggat 2718 aaatgccttg aagttagcag ggtgtatttt tttagcgaat atgatttgca tgtcttgcca 2778 ggagttaagc ggcctctggg gtgttgggga aatactttat ttctttccat ttattttttg 2838 tggggcgggg ataggggagg gcattgaagt tctacaattc tggaatagtt agttgatggt 2898 acatagttaa cttggcttcg gttacatatt ggactttaac aactgaagaa tctatgcgtg 2958 tcatttaaag aaaagttgca gaacaagcaa ttggcttaga tatacaatct ggaaaaatat 3018 tcctgtgccc atattttaat gtaattgtat aactgggagc aaaaatatat tctgcttttc 3078 aactgtaggt gctccagact tgctctccgt cactaacact aaatgtgctg ttttccttgt 3138 ttttcatcaa acatttaaga caaacttaga cctttctgta aattatcttt taatttctca 3198 gcaaaatcta aaaggggaag aaaaaagtcc atgaaaacta aaacttttca tgtttttagc 3258 cagtgagaag ataataaacc ctgactgtag aaggtgtgtt ttcatgcaaa ctatacttct 3318 gagcttgtta gcttctaatt atatcttaat aaatatattt tattactag 3367 <210> 20 <211> 695 <212> PRT <213> Homo sapiens <400> 20 Met Glu Glu Lys Pro Gly Gln Pro Gln Pro Gln His His His Ser His 1 5 10 15 His His Pro His His His Pro Gln Gln Gln Gln Gln Gln Pro His His 20 25 30 His His His Tyr Tyr Phe Tyr Asn His Ser His Asn His His His His 35 40 45 His His His Gln Gln Pro His Gln Tyr Leu Gln His Gly Ala Glu Gly 50 55 60 Ser Pro Lys Ala Gln Pro Lys Pro Leu Lys His Glu Gln Lys His Thr 65 70 75 80 Leu Gln Gln His Gln Glu Thr Pro Lys Lys Lys Thr Gly Tyr Gly Glu 85 90 95 Leu Asn Gly Asn Ala Gly Glu Arg Glu Ile Ser Leu Lys Asn Leu Ser 100 105 110 Ser Asp Glu Ala Thr Asn Pro Ile Ser Arg Val Leu Asn Gly Asn Gln 115 120 125 Gln Val Val Asp Thr Ser Leu Lys Gln Thr Val Lys Ala Asn Thr Phe 130 135 140 Gly Lys Ala Gly Ile Lys Thr Lys Asn Phe Ile Gln Lys Asn Ser Met 145 150 155 160 Asp Lys Lys Asn Gly Lys Ser Tyr Glu Asn Lys Ser Gly Glu Asn Gln 165 170 175 Ser Val Asp Lys Ser Asp Thr Ile Pro Ile Pro Asn Gly Val Val Thr 180 185 190 Asn Asn Ser Gly Tyr Ile Thr Asn Gly Tyr Met Ser Lys Gly Ala Asp 195 200 205 Asn Asp Gly Ser Gly Ser Glu Ser Gly Tyr Thr Thr Pro Lys Lys Arg 210 215 220 Lys Ala Arg Arg Asn Ser Ala Lys Gly Cys Glu Asn Leu Asn Ile Val 225 230 235 240 Gln Asp Lys Ile Met Gln Gln Glu Thr Ser Val Pro Thr Leu Lys Gln 245 250 255 Gly Leu Glu Thr Phe Lys Pro Asp Tyr Ser Glu Gln Lys Gly Asn Arg 260 265 270 Val Asp Gly Ser Lys Pro Ile Trp Lys Tyr Glu Thr Gly Pro Gly Gly 275 280 285 Thr Ser Arg Gly Lys Pro Ala Val Gly Asp Met Leu Arg Lys Ser Ser 290 295 300 Asp Ser Lys Pro Gly Val Ser Ser Lys Lys Phe Asp Asp Arg Pro Lys 305 310 315 320 Gly Lys His Ala Ser Ala Val Ala Ser Lys Glu Asp Ser Trp Thr Leu 325 330 335 Phe Lys Pro Pro Pro Val Phe Pro Val Asp Asn Ser Ser Ala Lys Ile 340 345 350 Val Pro Lys Ile Ser Tyr Ala Ser Lys Val Lys Glu Asn Leu Asn Lys 355 360 365 Thr Ile Gln Asn Ser Ser Val Ser Pro Thr Ser Ser Ser Ser Ser Ser 370 375 380 Ser Ser Thr Gly Glu Thr Gln Thr Gln Ser Ser Ser Arg Leu Ser Gln 385 390 395 400 Val Pro Met Ser Ala Leu Lys Ser Val Thr Ser Ala Asn Phe Ser Asn 405 410 415 Gly Pro Val Leu Ala Gly Thr Asp Gly Asn Val Tyr Pro Pro Gly Gly 420 425 430 Gln Pro Leu Leu Thr Thr Ala Ala Asn Thr Leu Thr Pro Ile Ser Ser 435 440 445 Gly Thr Asp Ser Val Leu Gln Asp Met Ser Leu Thr Ser Ala Ala Val 450 455 460 Glu Gln Ile Lys Thr Ser Leu Phe Ile Tyr Pro Ser Asn Met Gln Thr 465 470 475 480 Met Leu Leu Ser Thr Ala Gln Val Asp Leu Pro Ser Gln Thr Asp Gln 485 490 495 Gln Asn Leu Gly Asp Ile Phe Gln Asn Gln Trp Gly Leu Ser Phe Ile 500 505 510 Asn Glu Pro Ser Ala Gly Pro Glu Thr Val Thr Gly Lys Ser Ser Glu 515 520 525 His Lys Val Met Glu Val Thr Phe Gln Gly Glu Tyr Pro Ala Thr Leu 530 535 540 Val Ser Gln Gly Ala Glu Ile Ile Pro Ser Gly Thr Glu His Pro Val 545 550 555 560 Phe Pro Lys Ala Tyr Glu Leu Glu Lys Arg Thr Ser Pro Gln Val Leu 565 570 575 Gly Ser Ile Leu Lys Ser Gly Thr Thr Ser Glu Ser Gly Ala Leu Ser 580 585 590 Leu Glu Pro Ser His Ile Gly Asp Leu Gln Lys Ala Asp Thr Ser Ser 595 600 605 Gln Gly Ala Leu Val Phe Leu Ser Lys Asp Tyr Glu Ile Glu Ser Gln 610 615 620 Asn Pro Leu Ala Ser Pro Thr Asn Thr Leu Leu Gly Ser Ala Lys Glu 625 630 635 640 Gln Arg Tyr Gln Arg Gly Leu Glu Arg Asn Asp Ser Trp Gly Ser Phe 645 650 655 Asp Leu Arg Ala Ala Ile Val Tyr His Thr Lys Glu Met Glu Ser Ile 660 665 670 Trp Asn Leu Gln Lys Gln Asp Pro Lys Arg Ile Ile Thr Tyr Asn Glu 675 680 685 Ala Met Asp Ser Pro Asp Gln 690 695[Sequence List] SEQUENCE LISTING <110> Japan Science and Technology Corporation <120> Human Proteins and cDNAs then (8) <130> NP00037-YS <140> <141> <160> 20 <170> PatentIn Ver. 2.1 <210> 1 <211> 1354 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (133) .. (870) <400> 1 acccctcccc ctccccgcgg taccttgcac ttttctccct ccctgccccc tctcgagtcc 60 accctccggg ccttctgccc ctgatcgctt ggttttcctt gcagtcgcct gctgctgtcg gctgctgtcg gttggat Agg Atg ag gat Ag gat Ag gat Ag gat Ag gat Ag gat Ag gat Ag gat Ag gat Ag gag Agg gtt cca aga cca att ccc cac ata ggg cct gat tac att cca aca gag 219 Val Pro Arg Pro Ile Pro His Ile Gly Pro Asp Tyr Ile Pro Thr Glu 15 20 25 gaa gaa agg aga gtc ttc gca gaa tgc aat gat gaa agc ttc tgg ttc 267 Glu Glu Arg Arg Val Phe Ala Glu Cys Asn Asp Glu Ser Phe Trp Phe 30 35 40 45 aga tct gtg cct ttg gct gca aca agt atg ttg att act caa gga tta 315 Arg Ser Val Pro Leu Ala Ala Thr Ser Met Leu Ile Thr Gln Gly Leu 50 55 60 att agt aaa gga ata ctt tca agt cat ccc aaa tat ggt tcc atc cct 363 Ile Ser Lys Gly Ile Leu Ser Ser His Pro Lys Tyr Gly Ser Ile Pro 65 70 75 aaa ctt ata ctt gct tgt atc atg gga tac ttt gct gga aaa ctt tct 411 Lys Leu Ile Leu Ala Cys Ile Met Gly Tyr Phe Ala Gly Lys Leu Ser 80 85 90 tat gtg aaa act tgc caa gag aaa ttc aag aaa ctt gaa aat tcc ccc 459 Tyr Val Lys Thr Cys Gln Glu Lys Phe Lys Lys Leu Glu Asn Ser Pro 95 100 105 ctt gga gaa gct tta cga tca gga caa gca cga cga tct tca cca cct 507u Gly Glu Ala Leu Arg Ser Gly Gln Ala Arg Arg Ser Ser Pro Pro 110 115 120 125 ggg cac tat tat caa aag tca aaa tat gac tca agt gtg agt ggt caa 555 Gly His Tyr Tyr Gln Lys Ser Lys Tyr Asp Ser Ser Val Ser Gly Gln 130 135 140 tca tct ttt gtg aca tcc cca gca gca gac aac ata gaa atg ctt cct 603 Ser Ser Phe Val Thr Ser Pro Ala Ala Asp Asn Ile Glu Met Leu Pro 145 150 155 cat tat gag cca att cca ttc agt tct tct atg aat gaa tct gct ccc 651 His Tyr Glu Pro Ile Pro Phe Ser Ser Ser Met Asn Glu Ser Ala Pro 160 165 170 act ggt att act gat cat att gtc caa gga cct gat ccc aac ctt gaa 699 Thr Gly Ile Thr Asp His Ile Val Gln Gly Pro Asp Pro Asn Leu Glu 175 180 185 gaa agt cct aaa aga aaa aat att aca tat gag gaa tta agg aat aag 747 Glu Ser Pro Lys Arg Lys Asn Ile Thr Tyr Glu Glu Leu Arg Asn Lys 190 195 200 205 a ac aga gag tca tat gaa gta tct tta aca caa aag act gac ccc tca 795 Asn Arg Glu Ser Tyr Glu Val Ser Leu Thr Gln Lys Thr Asp Pro Ser 210 215 220 gtc agg cct atg cat gaa aga gtg cca aaa aaa gaa gtc aaa gta aac 843 Val Arg Pro Met His Glu Arg Val Pro Lys Lys Glu Val Lys Val Asn 225 230 235 aag tat gga gat act tgg gat gag tga aaaattacat cattggacat 890 Lys Tyr Gly Asp Thr Trp Asp Glu 240 245 gaaggagttt caacat ccg cttcatg 950 cagcagcagt cttcataaac acatttaaaa caagatcctg ggtttttgtg gtttgacttc 1010 tatggtgttt taaaaaaaca cagattttta gtgttaatat tgtgtaaatg tactcacctt 1070 agggattcat ttgaatgatg gtattatacc atgattgtat acagtttgtg aaattgttgc 1130 aagggcaaag ataactctta aaaaaccgtc gagattacaa tgctctagaa tcagcatata 1190 agaaaataaa tgatatctgc atgttgaatt ggggtggatg gggggagcaa gcataatttt 1250 taagtgtgaa gctttgcatc aagaaattat taaaaagctt tttttctcca gtattttctg 1310 tattatctta atgtttatgg caaataaaat gtaaaggaac atgc 1354 <210> 2 <211> 245 <212> PRT <213> Homo sapiens <400> 2 Met Asn Gly Arg Ala Asp Phe Arg Glu Pro Asn Ala Glu Val Pro Arg 1 5 10 15 Pro Ile Pro His Ile Gly Pro Asp Tyr Ile Pro Thr Glu Glu Glu Arg 20 25 30 Arg Val Phe Ala Glu Cys Asn Asp Glu Ser Phe Trp Phe Arg Ser Val 35 40 45 Pro Leu Ala Ala Thr Ser Met Leu Ile Thr Gln Gly Leu Ile Ser Lys 50 55 60 Gly Ile Leu Ser Ser His Pro Lys Tyr Gly Ser Ile Pro Lys Leu Ile 65 70 75 80 Leu Ala Cys Ile Met Gly Tyr Phe Ala Gly Lys Leu Ser Tyr Val Lys 85 90 95 Thr Cys Gln Glu Lys Phe Lys Lys Leu Glu Asn Ser Pro Leu Gly Glu 100 105 110 Ala Leu Arg Ser Gly Gln Ala Arg Arg Ser Ser Pro Pro Gly His Tyr 115 120 125 Tyr Gln Lys Ser Lys Tyr Asp Ser Ser Val Ser Gly Gln Ser Ser Phe 130 135 140 Val Thr Ser Pro Ala Ala Asp Asn Ile Glu Met Leu Pro His Tyr Glu 145 150 155 160 Pro Ile Pro Phe Ser Ser Ser Met Asn Glu Ser Ala Pro Thr Gly Ile 165 170 175 Thr Asp His Ile Val Gln Gly Pro Asp Pro Asn Leu Glu Glu Ser Pro 180 185 190 Lys Arg Lys Asn Ile Thr Tyr Glu Glu Leu Arg Asn Lys Asn Arg Glu 195 200 205 Ser Tyr Glu V al Ser Leu Thr Gln Lys Thr Asp Pro Ser Val Arg Pro 210 215 220 Met His Glu Arg Val Pro Lys Lys Glu Val Lys Val Asn Lys Tyr Gly 225 230 235 240 Asp Thr Trp Asp Glu 245 <210> 3 <211> 653 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (170) .. (502) <400> 3 cagaagaggt agggcgccgc cgtgacagat tagtcctaaa gggaacgggg ttgttagttc 60 aattggctac cggaaaaaac caggctgggc tgggcgccgc catgacaacc gataccggaa 120 aaggcgggtc gttccccccg gacagcccta cgccggcaaa ggtctcgag atg cag gcg 178 Met Gln Ala 1 gcc cta gag gtc acc gct cgc tac tgt ggc cgg gag ctg gag cag tat 226 Ala Leu Glu Val Thr Ala Arg Tyr Cys Gly Arg Glu Leu Glu Gln Tyr 5 10 15 ggc cag tgt gtg gcg gcc aag ccg gaa tcc tgg cag cgg gac tgt cac 274 Gly Gln Cys Val Ala Ala Lys Pro Glu Ser Trp Gln Arg Asp Cys His 20 25 30 35 tac ctt aag atg agc att gcc cag tgc aca tcc tcc cac cca atc atc 322 Tyr Leu Lys Met Ser Ile Ala Gln Cys Thr Ser Ser His Pro Ile Ile 40 45 50 cgc cag atc cgc cag gcc tgt gct cag cct ttt gag gcc ttc gag gag 370 Arg Gln Ile Arg Gln Ala Cys Ala Gln Pro Phe Glu Ala Phe Glu Glu 55 60 65 tgt ctt cga cag aac gag gca gct gtg ggc aac tgt gca gag cat atg 418 Cys Leu Arg Gln Asn Gla Ala Val Gly Asn Cys Ala Glu His Met 70 75 80 cgc cgc ttc ctg cag tgc gct gag cag gtg cag ccg cca cgc tca cc t 466 Arg Arg Phe Leu Gln Cys Ala Glu Gln Val Gln Pro Pro Arg Ser Pro 85 90 95 gca act gtg gag gca cag cca ctt cct gcc tcc tga ggactcctct 512 Ala Thr Val Glu Ala Gln Pro Leu Pro Ala Ser 100 105 110 gacggcagga aaactggaca tgaatgactg cccccccgcc cctcccctgc agagtggcca 572 gatggagtcc tgagccctgg acatgggccc ggctttcctg gatatcagga cttccaataa 632 ataaagactc tgtatactgg g 653 <210> 4 <211> 110 <212> PRT <213> Homo sapiens <400> 4 Met Gln Ala Ala Leu Glu Val Thr Ala Arg Tyr Cys Gly Arg Glu Leu 1 5 10 15 Glu Gln Tyr Gly Gln Cys Val Ala Ala Lys Pro Glu Ser Trp Gln Arg 20 25 30 Asp Cys His Tyr Leu Lys Met Ser Ile Ala Gln Cys Thr Ser Ser His 35 40 45 Pro Ile Ile Arg Gln Ile Arg Gln Ala Cys Ala Gln Pro Phe Glu Ala 50 55 60 Phe Glu Glu Cys Leu Arg Gln Asn Glu Ala Ala Val Gly Asn Cys Ala 65 70 75 80 Glu His Met Arg Arg Phe Leu Gln Cys Ala Glu Gln Val Gln Pro Pro 85 90 95 Arg Ser Pro Ala Thr Val Glu Ala Gln Pro Leu Pro Ala Ser 100 105 110 <210> 5 <211> 643 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (40) .. (411) <400> 5 gcggaagtac ggaccgtgaa ctggagtgga atcgcgact atg gga gct ccg ggg 54 Met Gly Ala Pro Gly 1 5 gga aag atc aac cgg ccc cga acg gag ctg aag aag aag ctg ttc aaa Lys Lyg Ars Lug Lys Leu Phe Lys 10 15 20 cgc cgg cgg gtg ttg aat cgg gag cgg cgt ctg agg cac cgg gtg gtc 150 Arg Arg Arg Val Leu Asn Arg Glu Arg Arg Leu Arg His Arg Val Val 25 30 35 ggg gct gtg ata gac caa ggg ctg atc acg cgg cac cac ctc aag aag 198 Gly Ala Val Ile Asp Gln Gly Leu Ile Thr Arg His His Leu Lys Lys 40 45 50 cgg gcg tcc agt gca cgt gcc aac att aca ctg tca ggg aag aag cgc 246 Arg Ala Ser Ser Ala Arg Ala Asn Ile Thr Leu Ser Gly Lys Lys Arg 55 60 65 aga aaa ctc ctc cag cag atc cgg ctt gcc cag aaa gag aag aca gcc 294 Arg Lys Leu Leu Gln Gln Ile Arg Leu Ala Gln Lys Glu Lys Thr Ala 70 75 80 85 atg gaa gtg gaa gcc cct tca aag cca gcc agg act agt gaa cca cag 342 Met Glu Val Glu Ala Pro Ser Lys Pro Ala Arg Thr Ser Glu Pro Gln 90 95 100 ctc aaa agg caa aag aag aca aaa gcc ccc cag gat gta gaa atg aag 390 Leu Lys Arg Gln Lys Lys Thr Lys Ala Pro Gln Asp Val Glu Met Lys 105 110 115 gac ctt gaa gat gag agc taa acctcttcca ctagaagatt ctcaactgga 441 Asp Leu Glu Asp Glu Ser 120 gccagccgcctgcctgcctgcctgcctgcc cctaatggcc tactgacctc ccctagaggg atgtctttgg 561 gagggaagaa ggtacagaag aaagattgga gaagggtctc tctagcagtc aactccattt 621 gtaataaagc cctagcactc tg 643 <210> 6 <211> 123 <212> PRT <213> Homo sapiens <400> 6 Met Gly Ala Pro Gly Gly Lys Ile Asn Arg Pro Arg Thr Glu Leu Lys 1 5 10 15 Lys Lys Leu Phe Lys Arg Arg Arg Val Leu Asn Arg Glu Arg Arg Leu 20 25 30 Arg His Arg Val Val Gly Ala Val Ile Asp Gln Gly Leu Ile Thr Arg 35 40 45 His His Leu Lys Lys Arg Ala Ser Ser Ala Arg Ala Asn Ile Thr Leu 50 55 60 Ser Gly Lys Lys Arg Arg Lys Leu Leu Gln Gln Ile Arg Leu Ala Gln 65 70 75 80 Lys Glu Lys Thr Ala Met Glu Val Glu Ala Pro Ser Lys Pro Ala Arg 85 90 95 Thr Ser Glu Pro Gln Leu Lys Arg Gln Lys Lys Thr Lys Ala Pro Gln 100 105 110 Asp Val Glu Met Lys Asp Leu Glu Asp Glu Ser 115 120 <210> 7 <211> 1293 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (306) .. (1019) <400> 7 gttaggctga gcctcttgct tgctgtgact ggtggagctg ccgcgctgtc cgcgttatct 60 cctcccggtg agaacgaacc gcagtgtcca ccggcgagga gccagccctg tcccggtcag 120 agaaagacga cgaggatacc tgggagcggg cggcggccgg gctgggccgc gccggtgcgg 180 gctggcgact ctgctcctcc gcttgctgct gtctctggga actgggtgcc agcgctgagg 240 ggcttccagc ggacagggac ccccttcccc ggctcccctg cccaccctgc cggggagggc 300 ggaag atg ccg gtg aag aag aag aga aaa tcc cct ggg gtg gca gca gca 350 Met Pro Val Lys Lys Lys Arg Lys Ser Pro Gly Val Ala Ala Ala 1 5 10 15 gta gcg gaa gac gga ggc ctc aaa aag tgt aaa atc tcc agc tat tgc 398 Val Ala Glu Asp Gly Gly Leu Lys Lys Cys Lys Ile Ser Ser Tyr Cys 20 25 30 aga tcc caa ccc cct gct aga cta ata agt gga gag gaa cat ttt tca 446 Arg Ser Gln Pro Pro Ala Arg Leu Ile Ser Gly Glu Glu His Phe Ser 35 40 45 agc aag aag tgc ctg gct tgg ttt tat gaa tat gca ggt cct gat gaa 494 Ser Lys Lys Cys Leu Ala Trp Phe Tyr Glu Tyr Ala Gly Pro Asp Glu 50 55 60 gtt gta ggg cca gaa gga atg gaa aaa ttt tgt gaa gtt att gt Val Val Gly Pro Glu Gly Met Glu Lys Phe Cys Glu Asp Ile Gly Val 65 70 75 gaa cct gaa aat att att atg tta gtt tta gcg tgg aaa ttg gag gct 590 Glu Pro Glu Asn Ile Ile Met Leu Val Leu Ala Trp Lys Leu Glu Ala 80 85 90 95 gaa agc atg gga ttt ttt acc aag gaa gaa tgg tta aag gga atg act 638 Glu Ser Met Gly Phe Phe Thr Lys Glu Glu Trp Leu Lys Gly Met Thr 100 105 110 tca tta cag tgt gac tgc aca gaa aag tta caa aac aaa ttt gac ttt 686 Ser Leu Gln Cys Asp Cys Thr Glu Lys Leu Gln Asn Lys Phe Asp Phe 115 120 125 ttg cgc tca cag ttg aat gat att tcg tca ttt aag aat atc tac aga 734 Leu Arg Ser Gln Leu Asn Asle Ser Ser Phe Lys Asn Ile Tyr Arg 130 135 140 tat gcc ttt gat ttt gca agg gat aaa gat cag aga agc ctt gat att 782 Tyr Ala Phe Asp Phe Ala Arg Asp Lys Asp Gln Arg Ser Leu Asp Ile 145 150 155 gat act gct aaa tct atg tta gct ctt ctg ctt ggg agg aca tgg cca 830 Asp Thr Ala Lys Ser Met Leu Ala Leu Leu Leu Gly Arg Thr Trp Pro 160 165 170 175 ctg ttt tca gta ttt tac cag tac ctg gag caa tca aag tat cgt gtt 878 Le u Phe Ser Val Phe Tyr Gln Tyr Leu Glu Gln Ser Lys Tyr Arg Val 180 185 190 atg aac aaa gat caa tgg tac aat gta tta gaa ttc agc aga aca gtc 926 Met Asn Lys Asp Gln Trp Tyr Asn Val Leu Glu Phe Ser Arg Thr Val 195 200 205 cat gct gat ctt agt aac tat gat gaa gat ggt gct tgg cct gtt ctt 974 His Ala Asp Leu Ser Asn Tyr Asp Glu Asp Gly Ala Trp Pro Val Leu 210 215 220 ctt gat gaa ttt gtt gag tgg caa aaa gtc cgt cag aca tca tag 1019 Leu Asp Glu Phe Val Glu Trp Gln Lys Val Arg Gln Thr Ser 225 230 235 caagaactat gtgaagaaaa tgcaaacctt tcaattccca cgtgtataca agctaatgtg 1079 atgaggggga aaaaaatcca acgggtgcat tttcattcat atgaaagact tctcatagta 1139 cttttttttc ctttttttaa aggaggtttt tcttgttaca tgtgatgggc attgagccac 1199 acctcttctt agactgaata ttgaagtttt tgttttgagt tatgtttata acatttattt 1259 cagaacaata aagattcaga tttgtgacaa aggc 1293 <210> 8 <211> 237 <212> PRT <213> Homo sapiens <400> 8 Met Pro Val Lys Lys Lys Arg Lys Ser Pro Gly Val Ala Ala Ala Val 1 5 10 15 Ala Glu Asp Gly Gly Leu Lys Lys Cys Lys Ile Ser Ser Tyr Cys Arg 20 25 30 Ser Gln Pro Pro Ala Arg Leu Ile Ser Gly Glu Glu His Phe Ser Ser 35 40 45 Lys Lys Cys Leu Ala Trp Phe Tyr Glu Tyr Ala Gly Pro Asp Glu Val 50 55 60 Val Gly Pro Glu Gly Met Glu Lys Phe Cys Glu Asp Ile Gly Val Glu 65 70 75 80 Pro Glu Asn Ile Ile Met Leu Val Leu Ala Trp Lys Leu Glu Ala Glu 85 90 95 Ser Met Gly Phe Phe Thr Lys Glu Glu Trp Leu Lys Gly Met Thr Ser 100 105 110 Leu Gln Cys Asp Cys Thr Glu Lys Leu Gln Asn Lys Phe Asp Phe Leu 115 120 125 Arg Ser Gln Leu Asn Asp Ile Ser Ser Phe Lys Asn Ile Tyr Arg Tyr 130 135 140 Ala Phe Asp Phe Ala Arg Asp Lys Asp Gln Arg Ser Leu Asp Ile Asp 145 150 155 160 Thr Ala Lys Ser Met Leu Ala Leu Leu Leu Gly Arg Thr Trp Pro Leu 165 170 175 Phe Ser Val Phe Tyr Gln Tyr Leu Glu Gln Ser Lys Tyr Arg Val Met 180 185 190 Asn Lys Asp Gln Trp Tyr Asn Val Leu Glu Phe Ser Arg Thr Val His 195 200 205 Ala Asp Leu S er Asn Tyr Asp Glu Asp Gly Ala Trp Pro Val Leu Leu 210 215 220 Asp Glu Phe Val Glu Trp Gln Lys Val Arg Gln Thr Ser 225 230 235 <210> 9 <211> 916 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (148) .. (471) <400> 9 ctctctcggt ttgtctgggt catcttgtct gcccgccgct ggcctggccc cgtctgtctc 60 tctcagcagc tgtctttctc gcgcccactg gccggtctct cctcttcccc gcagttgcct 120 ccttctctgc ctgcctgggt ggccgcc atg ggc cgg aag cgg ctc atc act gat 174 Met Gly Arg Lys Arg Leu Ile Thr Asp 1 5 tcc tac ccg gtt gtg aag agg agg gag ggg ccc gct ggg cac agc aag 222 Ser Tyr Pro Val Val Lys Arg Arg Glu Gly Pro Ala Gly His Ser Lys 10 15 20 25 ggg gag ctg gca ccc gag cta ggg gag gag ccc cag ccc cgc gac gag 270 Gly Glu Leu Ala Pro Glu Leu Gly Glu Glu Pro Gln Pro Arg Asp Glu 30 35 40 gag gaa gcg gag ctg gag ctg ctg agg cag ttt gac ctg gcc tgg cag 318 Glu Glu Ala Glu Leu Glu Leu Leu Arg Gln Phe Asp Leu Ala Trp Gln 50 55 tac ggg ccc tgc acc ggg atc aca cgg ctg cag cgc tgg tgt cgg gcc 366 Tyr Gly Pro Cys Thr Gly Ile Thr Arg Leu Gln Arg Trp Cys Arg Ala 60 65 70 aag cag atg ggc ttg gag cct ccc cca gag ggg cag gtg ctg aag 414 Lys Gln Met Gly Leu Glu Pro Pro Glu Val Trp Gln Val Leu Lys 75 80 85 acc cac ccc gga gac ccc cgc ttc cag tgc agt ctc tgg cat ctc tat 462 Thr His Pro Gly Asp Pro Arg Phe Gln Cys Ser Leu Trp His Leu Tyr 90 95 100 105 ccc cta tga ggcaccacgt aagacctcct gcccttagct ctcttgctca 511 Pro Leu ccacccaaga acctcaggac agaagcgaga gcccattgct cctgctcagc tcagcccggc 571 tgcggaggaa cccttggcag gcagaacctg gaggtgtcag aggctcaact cctccatcta 631 accagcaggc tcccagagtc cccggaagag cctgcgcagc tgaagcagag tgcttctaga 691 tggagagtgg tcactgggga aaaggacctg gccatcacct tccaatacct gctgcctgtc 751 tccctgaccc atgatctggc aagttaggca cagtcagaca tggacagttg atccatgagg 811 aaaagatgct ctcccaccta aggccaggaa tctgagagca ggactggctg agctcccagg 871 gcaaggggtt cactaatgct tatcaataaa gaatattgag cctgg 916 <210> 10 <211> 107 <212> PRT <213> Homo sapiens <400> 10 Met Gly Arg Lys Arg Leu Ile Thr Asp Ser Tyr Pro Val Val Lys Arg 1 5 10 15 Arg Glu Gly Pro Ala Gly His Ser Lys Gly Glu Leu Ala Pro Glu Leu 20 25 30 Gly Glu Glu Pro Gln Pro Arg Asp Glu Glu Glu Ala Glu Leu Glu Leu 35 40 45 Leu Arg Gln Phe Asp Leu Ala Trp Gln Tyr Gly Pro Cys Thr Gly Ile 50 55 60 Thr Arg Leu Gln Arg Trp Cys Arg Ala Lys Gln Met Gly Leu Glu Pro 65 70 75 80 Pro Pro Glu Val Trp Gln Val Leu Lys Thr His Pro Gly Asp Pro Arg 85 90 95 Phe Gln Cys Ser Leu Trp His Leu Tyr Pro Leu 100 105 <210> 11 <211> 1002 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (51) .. (731) <400> 11 ctattttctc acctggttcc cgcggcgagc cagcggcagc ggcggcgcg atg aga 56 Met Arg 1 cag aag cac tac ctt gag gct gca gcg cgg gga ctg cac gac agc tgc 104 Gln Lys His Tyr Leu Alu Ala Ag La Ag La Ag La Ag 15 ccg ggc caa gcc cgc tac ctc ctt ctc ttt ctc ttt tac agc tgg gcc 152 Pro Gly Gln Ala Arg Tyr Leu Leu Leu Phe Leu Phe Tyr Ser Trp Ala 20 25 30 tac act tcg tcg cac gat gat aag agc act tatt acg tgt cca 200 Tyr Thr Ser Ser His Asp Asp Lys Ser Thr Phe Glu Glu Thr Cys Pro 35 40 45 50 tac tgt ttc cag ctg ttg gtt ctg gat aac tct cga gtg cgt ctc aaa 248 Tyr Cys Phe Gln Leu Leu Val Leu Asp Asn Ser Arg Val Arg Leu Lys 55 60 65 ccc aaa gcc agg ttg aca ccc aaa ata cag aaa ctt ctt aat cga gaa 296 Pro Lys Ala Arg Leu Thr Pro Lys Ile Gln Lys Leu Leu Asn Arg Glu 70 75 80 gcg aga aac tat aca ctc agt ttt aaa gaa gca aaa atg gtg aaa aag 344 Ala Arg Asn Tyr Thr Leu Ser Phe Lys Glu Ala Lys Met Val Lys Lys 85 90 95 ttc aaa gac tcc aaa agt gta ttg ttg atc act tgt aaa aca tgc aac 39 2 Phe Lys Asp Ser Lys Ser Val Leu Leu Ile Thr Cys Lys Thr Cys Asn 100 105 110 aga aca gtg aaa cat cat ggt aaa agt aga agc ttt gtg tca aca ttg 440 Arg Thr Val Lys His His Gly Lys Ser Arg Ser Phe Val Ser Thr Leu 115 120 125 130 aag agc aat cct gcc act cct aca agt aaa ctc agc ctg aag aca cca 488 Lys Ser Asn Pro Ala Thr Pro Thr Ser Lys Leu Ser Leu Lys Thr Pro 135 140 145 gag aga agg act gca aac cca aat cat gac atg tct ggc tcg aaa ggc 536 Glu Arg Arg Thr Ala Asn Pro Asn His Asp Met Ser Gly Ser Lys Gly 150 155 160 aag agc cca gca tcg gtt ttc aga aca cct aca tct gga cag tca gta 584 Lys Ser Pro Ala Ser Val Phe Arg Thr Pro Thr Ser Gly Gln Ser Val 165 170 175 tct act tgc tcc tca aag aac acc agc aaa aca aag aaa cac ttc tct 632 Ser Thr Cys Ser Ser Lys Asn Thr Ser Lys Thr Lys Lys His Phe Ser 180 185 190 caa cta aaa atg tta ctt agt cag aat gaa tcc caa aag att cca aag 680 Gln Leu Lys Met Leu Leu Ser Gln Asn Glu Ser Gln Lys Ile Pro Lys 195 200 205 210 gtg gac ttc aga aat ttc tta tct tct ctg aaggt gg a ctt tta aaa 728 Val Asp Phe Arg Asn Phe Leu Ser Ser Leu Lys Gly Gly Leu Leu Lys 215 220 225 taa gaaatgcctg atgtcaattc tgaaactaaa gttggtaaaa caacttttta 781 aactcttatt cattttttga atacatggaa actagatctg aatgcaaact tttcttggca 841 tccttcagtg tttatgggga aaatacctca ttagtgtgaa tacctgaaac ctgcctacct 901 cataggacag ctgtgaggat caaaaaatat atgaaagttc cttgtagata catatctata 961 gatatatatg tgtatgtata taaagataga tatatacatt g 1002 <210> 12 <211> 226 <212> PRT <213> Homo sapiens <400> 12 Met Arg Gln Lys His Tyr Leu Glu Ala Ala Ala Arg Gly Leu His Asp 1 5 10 15 Ser Cys Pro Gly Gln Ala Arg Tyr Leu Leu Leu Phe Leu Phe Tyr Ser 20 25 30 Trp Ala Tyr Thr Ser Ser His Asp Asp Lys Ser Thr Phe Glu Glu Thr 35 40 45 Cys Pro Tyr Cys Phe Gln Leu Leu Val Leu Asp Asn Ser Arg Val Arg 50 55 60 Leu Lys Pro Lys Ala Arg Leu Thr Pro Lys Ile Gln Lys Leu Leu Asn 65 70 75 80 Arg Glu Ala Arg Asn Tyr Thr Leu Ser Phe Lys Glu Ala Lys Met Val 85 90 95 Lys Lys Phe Lys Asp Ser Lys Ser Val Leu Leu Ile Thr Cys Lys Thr 100 105 110 Cys Asn Arg Thr Val Lys His His Gly Lys Ser Arg Ser Phe Val Ser 115 120 125 Thr Leu Lys Ser Asn Pro Ala Thr Pro Thr Ser Lys Leu Ser Leu Lys 130 135 140 Thr Pro Glu Arg Arg Thr Ala Asn Pro Asn His Asp Met Ser Gly Ser 145 150 155 160 Lys Gly Lys Ser Pro Ala Ser Val Phe Arg Thr Pro Thr Ser Gly Gln 165 170 175 Ser Val Ser Thr Cys Ser Ser Lys Asn Thr Ser Lys Thr Lys Lys His 180 185 190 Phe Ser Gln Leu Lys Met Leu Leu Ser Gln Asn Glu Ser Gln Lys Ile 195 200 205 Pro Lys Val Asp Phe Arg Asn Phe Leu Ser Ser Leu Lys Gly Gly Leu 210 215 220 Leu Lys 225 <210> 13 <211> 1753 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (268) .. (1455) <400> 13 gcctttgttt acaaccctgc catgatctcc ctcttgcaaa agcgagggct acagaacagg 60 cattcaggag tcctgtgctc cagtcacagc cttttctgtt cttcagctag gagacaccaa 120 accctcagga agatttacta tagctaagag aaaactgcag cagaaagggc gcggctacct 180 acttcttaaa ttccgtttgt ggaccctcag actcttagtc ccctactccc agatacagcg 240 gccctaccgt ggctcctggc aagaagc atg gat ctc gga atc cct gac ctg ctg 294 Met Asp Leu Gly Ile Pro Asp Leu Leu 1 5 gac gcg tgg ctg gag ccc cca gag gat atc ttc tcg aca gga tcc gtc 342 Asp Ala Trp Leu Glu Pro Pro Glu Asp Ile Phe Ser Thr Gly Ser Val 10 15 20 25 ctg gag ctg gga ctc cac tgc ccc cct cca gag gtt ccg gta act agg 390 Leu Glu Leu Gly Leu His Cys Pro Pro Pro Glu Val Pro Val Thr Arg 30 35 40 cta cag gaa cag gga ctg caa ggc tgg aag tcc ggt ggg gac cgt ggc 438 Leu Gln Glu Gln Gly Leu Gln Gly Trp Lys Ser Gly Gly Asp Arg Gly 45 50 55 tgt ggc ctt caa gag agt gag cct gaa gat ttc ttg aag ctt ttc att 486 Cys Gly Leu Gln Glu Ser Glu Pro Glu Asp Phe Leu Lys Leu Phe Ile 60 65 70 gat ccc aat gag gtg tac tgc tca ga a gca tct cct ggc agt gac agt 534 Asp Pro Asn Glu Val Tyr Cys Ser Glu Ala Ser Pro Gly Ser Asp Ser 75 80 85 ggc atc tct gag gac ccc tgc cat cca gac agt ccc cct gcc ccc agg 582 Gly Ile Ser Glu Asp Pro Cys His Pro Asp Ser Pro Pro Ala Pro Arg 90 95 100 105 gca acc agt tct cct atg ctc tat gag gtt gtc tat gag gca ggg gcc 630 Ala Thr Ser Ser Pro Met Leu Tyr Glu Val Val Tyr Glu Ala Gly Ala 110 115 120 ctg gag agg atg cag ggg gaa act ggg cca aat gta ggc ctt atc tcc 678 Leu Glu Arg Met Gln Gly Glu Thr Gly Pro Asn Val Gly Leu Ile Ser 125 130 135 atc cag cta gat cag tgg agc cca gca ttt atg gtg cct gat tcc tgc 726 Ile Gln Leu Asp Gln Trp Ser Pro Ala Phe Met Val Pro Asp Ser Cys 140 145 150 atg gtc agt gag ctg ccc ttt gat gct cat gcc cac atc ctg ccc aga 774 Met Val Ser Glu Leu Pro Phe Asp Ala His Ala His Ile Leu Pro Arg 155 160 165 gca ggc acc gta gcc cca gtg ccc tgt aca acc ctg ctg ccc tgt caa 822 Ala Gly Thr Val Val Ala Pro Val Pro Cys Thr Thr Thr Leu Leu Pro Cys Gln 170 175 180 185 acc ctg ttg ttc ctg acc gat gag gag aag cgt ctg ctg ggg cag gaa ggg 870 Thr Leu Phe Leu Thr Asp Glu Glu Lys Arg Leu Leu Gly Gln Glu Gly 190 195 200 gtt tcc ctg ccc tct cac ctg ccc ctc acc aag gca gag gag agg gtc 918 Val Pro Ser His Leu Pro Leu Thr Lys Ala Glu Glu Arg Val 205 210 215 ctc aag aag gtc agg agg aaa atc cgt aac aag cag tca gct cag gac 966 Leu Lys Lys Val Arg Arg Lys Ile Arg Asn Lys Gln Ser Ala Gln Asp 220 225 230 agt cgg cgg cgg aag aag gag tac att gat ggg ctg gag agc agg gtg 1014 Ser Arg Arg Arg Lys Lys Glu Tyr Ile Asp Gly Leu Glu Ser Arg Val 235 240 245 gca gcc tgt tct gca cag aac caa gaa ttaca aaa gtc cag gag 1062 Ala Ala Cys Ser Ala Gln Asn Gln Glu Leu Gln Lys Lys Val Gln Glu 250 255 260 265 ctg gag agg cac aac atc tcc ttg gta gct cag ctc cgc cag ctg cag 1110 Leu Glu Arg His Asn Ile Ser Val Ala Gln Leu Arg Gln Leu Gln 270 275 280 acg cta att gct caa act tcc aac aaa gct gcc cag acc agc act tgt 1158 Thr Leu Ile Ala Gln Thr Ser Asn Lys Ala Ala Gln Thr Ser Thr Cys 285 290 295 295 gtt ttg att ctt ctt ttt tcc ctg gct ctc atc atc ctg ccc agc ttc 1206 Val Leu Ile Leu Leu Phe Ser Leu Ala Leu Ile Ile Leu Pro Ser Phe 300 305 310 agt cca ttc cag agt cga cca gaa gct ggg tct gag gat tac 1254 Ser Pro Phe Gln Ser Arg Pro Glu Ala Gly Ser Glu Asp Tyr Gln Pro 315 320 325 cac gga gtg act tcc aga aat atc ctg acc cac aag gac gta aca gaa 1302 His Gly Val Thr Ser Arg Asn Ile Leu Thr His Lys Asp Val Thr Glu 330 335 340 345 aat ctg gag acc caa gtg gta gag tcc aga ctg agg gag cca cct gga 1350 Asn Leu Glu Thr Gln Val Val Glu Ser Arg Leu Arg Glu Pro Gly 350 355 360 gcc aag gat gca aat ggc tca aca agg aca ctg ctt gag aag atg gga 1398 Ala Lys Asp Ala Asn Gly Ser Thr Arg Thr Leu Leu Glu Lys Met Gly 365 370 375 ggg aag cca aga ccc agt ggg cgc atc cgg tcc gtg ctg cat gca gat 1446 Gly Lys Pro Arg Pro Ser Gly Arg Ile Arg Ser Val Leu His Ala Asp 380 385 390 gag atg tga gctggaacag accttcctgg cccacttcct gatcacaagg 1495 Glu Met 395 aatcctgggc ttccttatgg ctttgcttcc cactgggatt cctacttagg tgtc tgccct 1555 caggggtcca aatcacttca ggacacccca agagatgtcc tttagtctct gcctgaggcc 1615 tagtctgcat ttgtttgcat atatgagagg gtacctcaaa tacttctgtgt atgtatctgt 1675 gattttatttt cttctttgattagttagttagttagttagttagttagttagttagttagttagttaga <210> 14 <211> 395 <212> PRT <213> Homo sapiens <400> 14 Met Asp Leu Gly Ile Pro Asp Leu Leu Asp Ala Trp Leu Glu Pro Pro 1 5 10 15 Glu Asp Ile Phe Ser Thr Gly Ser Val Leu Glu Leu Gly Leu His Cys 20 25 30 Pro Pro Glu Val Pro Val Thr Arg Leu Gln Glu Gln Gly Leu Gln 35 40 45 Gly Trp Lys Ser Gly Gly Asp Arg Gly Cys Gly Leu Gln Glu Ser Glu 50 55 60 Pro Glu Asp Phe Leu Lys Leu Phe Ile Asp Pro Asn Glu Val Tyr Cys 65 70 75 80 Ser Glu Ala Ser Pro Gly Ser Asp Ser Gly Ile Ser Glu Asp Pro Cys 85 90 95 His Pro Asp Ser Pro Pro Ala Pro Arg Ala Thr Ser Ser Pro Met Leu 100 105 110 Tyr Glu Val Val Tyr Glu Ala Gly Ala Leu Glu Arg Met Gln Gly Glu 115 120 125 Thr Gly Pro Asn Val Gly Leu Ile Ser Ile Gln Leu Asp Gln Trp Ser 130 135 140 Pro Ala Phe Met Val Pro Asp Ser Cys Met Val Ser Glu Leu Pro Phe 145 150 155 160 Asp Ala His Ala His Ile Leu Pro Arg Ala Gly Thr Val Ala Pro Val 165 170 175 Pro Cys Thr Thr Leu Leu Pro Cys Gln Thr Leu Phe Leu Thr Asp Glu 180 185 190 Glu Lys Arg Leu Leu Gly Gln Glu Gly Val Ser Leu Pro Ser His Leu 195 200 205 Pro Leu Thr Lys Ala Glu Glu Arg Val Leu Lys Lys Val Arg Arg Lys 210 215 220 Ile Arg Asn Lys Gln Ser Ala Gln Asp Ser Arg Arg Arg Lys Lys Glu 225 230 235 240 Tyr Ile Asp Gly Leu Glu Ser Arg Val Ala Ala Cys Ser Ala Gln Asn 245 250 255 Gln Glu Leu Gln Lys Lys Val Gln Glu Leu Glu Arg His Asn Ile Ser 260 265 270 Leu Val Ala Gln Leu Arg Gln Leu Gln Thr Leu Ile Ala Gln Thr Ser 275 280 285 Asn Lys Ala Ala Gln Thr Ser Thr Cys Val Leu Ile Leu Leu Phe Ser 290 295 300 300 Leu Ala Leu Ile Ile Leu Pro Ser Phe Ser Pro Phe Gln Ser Arg Pro 305 310 315 320 Glu Ala Gly Ser Glu Asp Tyr Gln Pro His Gly Val Thr Ser Arg Asn 325 330 335 Ile Leu Thr His Lys Asp Val Thr Glu Asn Leu Glu Thr Gln Val Val 340 345 350 Glu Ser Arg Leu Arg Glu Pro Pro Gly Ala Lys Asp Ala Asn Gly Ser 355 360 365 Thr Arg Thr Leu Leu Glu Lys Met Gly Gly Lys Pro Arg Pro Ser Gly 370 375 380 Arg Ile Arg Ser Val Leu His Ala Asp Glu Met 385 390 395 <210> 15 <211> 668 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (54) .. (122) <400> 15 ctttcttcct tttggtgcga gcttgctgtg gtttttgctc tgggtcctct ggg atg 56 Met 1 gcg cct ggc tgt ggc cgc gtg gtc tct cac gca ggg gcg ccg ggc ggg 104 Ala Pro Gly Cys Aly Gly Gly Aly G gga acg cgg cca ccc tga gtctggtgag tcgactgcgg cggcctgtgt 152 Gly Thr Arg Pro Pro 20 ccgaagtgtc cggggccgtg aacaagggca gcggcctggc ctcaggcctg cgttcccacg 212 tttggaaacg gggagcttcg tcgattttgt ttacatcatc gactatgcca gggagttctc 272 cagataagcc tggttttatt ttcgtcagtg aaaaggcctt accgtataac tgactttatg 332 cttgccctgc ccccgtataa aataacttaa aagcagcgtg cctggttaca gctgtttcca 392 cgtgcggtgc tcgtcgggag tgatcaccta ccctacaggt ggaagatgga tgcctgaagt 452 gtagactgct gctagctgaa taccatctgg gagcataaag gtgacctgaa ggatgtcctt 512 ggtgaggatt ttgaaaattt gatcttcaca agagttgcct ggatcatttg aaatttctgg 572 gagtctgagg agtactgaca taattacctg ctggcaatg ttaggagatag ttaggagatag ttaggagatag gg gg <210> 16 <211> 22 <212> PRT <213> Homo sapiens <400> 16 Met Ala Pro Gly Cys Gly Arg Val Val Ser His Ala Gly Ala Pro Gly 1 5 10 15 Gly Gly Thr Arg Pro Pro 20 <210> 17 <211> 279 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (27) .. (239) <400> 17 atccctctcc acgacctcgg tcgagc atg ttc acc agg gcc cag gtg aga cgg 53 Met Phe Thr Arg Ala Gln Val Arg Arg 1 5 att ctg cag cgg gtg ccc ggg aag cag cga ttt ggc atc tac cgg ttcln Ile Pro Gly Lys Gln Arg Phe Gly Ile Tyr Arg Phe 10 15 20 25 ctg ccc ttc ttt ttt gtc ctg gga gga acg atg gag tgg atc atg att 149 Leu Pro Phe Phe Phe Val Leu Gly Gly Thr Met Glu Trp Ile Met Ile 30 35 40 aaa gtg cgc gtg ggc cag gag acc ttc tat gat gtc tac cgt aga aaa 197 Lys Val Arg Val Gly Gln Glu Thr Phe Tyr Asp Val Tyr Arg Arg Lys 45 50 55 gcc tca gaa aga cag tat cag aga ag ctg gag tga 239 Ala Ser Glu Arg Gln Tyr Gln Arg Arg Leu Glu Asp Glu 60 65 70 gactgaactt cagcagtcaa taaagtcaat atgaattttt 279 <210> 18 <211> 70 <212> PRT <213> Homo sapiens <400> 18 Met Phe Thr Arg Ala Gln Val Arg Arg Ile Leu Gln Arg Val Pro Gly 1 5 10 15 Lys Gln Arg Phe Gly Ile Tyr Arg Phe Leu Pro Phe Phe Phe Phe Val Leu 20 25 30 Gly Gly Thr Met Glu Trp Ile Met Ile Lys Val Arg Val Gly Gln Glu 35 40 45 Thr Phe Tyr Asp Val Tyr Arg Arg Lys Ala Ser Glu Arg Gln Tyr Gln 50 55 60 Arg Arg Leu Glu Asp Glu 65 70 <210> 19 <211> 3367 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (91) .. (2178) <400> 19 cagatatact gagtgagccc tgagaagcag tctcagatcc tgacggtgca gcagcccgca 60 gcctcagcca gggagtccca gccgctttca atg gag gag aag ccc ggc cag cca 114 Met Glu Glu Lys Pro Gly Gln Pro 1 5 cag cct cag cac cat cac agc cac cac cat ccg cac cat cac cct cag 162 Gln Pro Gln His His His Ser His His His Pro His His His Pro Gln 10 15 20 cag cag cag cag cag ccg cac cac cac cac cat tat tat ttc tac aac 210 Gln Gln Gln Gln Gln Gln Pro His His His His Tyr Tyr Phe Tyr Asn 25 30 35 40 cac agc cac aac cac cac cac cac cat cat cac cag cag cct cac caa 258 His Ser His Asn His His His His His His Gln Gln Pro His Gln 45 50 55 tac ctg cag cat gga gcc gag ggc agc ccc aag gcc cag cca aag ccg 306 Tyr Leu Gln His Gly Ala Glu Gly Ser Pro Lys Ala Gln Pro Lys Pro 60 65 70 ctg aaa cat gag cag aaa cac acc ctc cag cag cac cag gaa acg ccg 354 Leu Lys His Glu Gln Lys His Thr Leu Gln Gln His Gln Glu Thr Pro 75 80 85 aag aag aaa aca ggc tat ggt gaa cta aac ggt aat gct gga gaa aga 402 Lys Lys Lys Thr Gly Tyr Gly Glu Leu Asn G ly Asn Ala Gly Glu Arg 90 95 100 gaa ata tct tta aag aac ctg agt tct gat gaa gcc acc aac cct att 450 Glu Ile Ser Leu Lys Asn Leu Ser Ser Asp Glu Ala Thr Asn Pro Ile 105 110 115 120 tcc agg gtc ctc aat ggc aac cag caa gtt gta gac act agc ctg aag 498 Ser Arg Val Leu Asn Gly Asn Gln Gln Val Val Asp Thr Ser Leu Lys 125 130 135 cag act gta aag gcc aac acc ttt ggg aaa gca gga att aaa acc aag 546 Gln Thr Val Lys Ala Asn Thr Phe Gly Lys Ala Gly Ile Lys Thr Lys 140 145 150 aat ttc att cag aaa aac agt atg gac aaa aag aat ggg aag tct tat 594 Asn Phe Ile Gln Lys Asn Ser Met Asp Lys Lys Asn Gly Lys Ser Tyr 155 160 165 gaa aat aaa tct gga gag aat cag tct gta gat aag tct gat act ata 642 Glu Asn Lys Ser Gly Glu Asn Gln Ser Val Asp Lys Ser Asp Thr Ile 170 175 180 cca att cca aat ggt gtg gta aca aat aat tct ggt tat att act aat 690 Pro Ile Pro Asn Gly Val Val Thr Asn Asn Ser Gly Tyr Ile Thr Asn 185 190 195 200 ggt tat atg agt aaa gga gca gat aat gat ggt agt gga tct gag agc 738 Gly Tyr Met Ser Lys Gly Al a Asp Asn Asp Gly Ser Gly Ser Glu Ser 205 210 215 gga tat aca act cct aaa aaa agg aaa gct agg cgc aat agt gcc aag 786 Gly Tyr Thr Thr Pro Lys Lys Arg Lys Ala Arg Arg Asn Ser Ala Lys 220 225 230 ggt tgt gaa aac ctt aat ata gtg cag gac aaa ata atg caa caa gag 834 Gly Cys Glu Asn Leu Asn Ile Val Gln Asp Lys Ile Met Gln Gln Glu 235 240 245 acc agt gtc cca acc tta aaa cag gga ctt gaa act ttc ag gac 882 Thr Ser Val Pro Thr Leu Lys Gln Gly Leu Glu Thr Phe Lys Pro Asp 250 255 260 tat agt gaa caa aag gga aat cga gta gat ggt tcg aag ccc att tgg 930 Tyr Ser Glu Gln Lys Gly Asn Arg Val Asp Gly Ser Lys Pro Ile Trp 265 270 275 280 280 aag tat gaa act ggg cct gga gga aca agt cga gga aaa cct gct gtg 978 Lys Tyr Glu Thr Gly Pro Gly Gly Thr Ser Arg Gly Lys Pro Ala Val 285 290 295 ggt gat atg ctt cgg aaa agc tca gat agt aaa cct ggt gtg agc agc 1026 Gly Asp Met Leu Arg Lys Ser Ser Asp Ser Lys Pro Gly Val Ser Ser 300 305 310 aaa aag ttt gat gat cgg ccc aaa gga aag cat gct tca gct gtt gcc 1074 Lys Lys PheAsp Asp Arg Pro Lys Gly Lys His Ala Ser Ala Val Ala 315 320 325 tcc aaa gag gac tcg tgg acc cta ttt aaa cca ccc cca gtt ttt cca 1122 Ser Lys Glu Asp Ser Trp Thr Leu Phe Lys Pro Pro Pro Val Phe Pro 330 335 340 gtg gac aat agc agt gct aaa ata gtt cct aaa ata agt tat gca agc 1170 Val Asp Asn Ser Ser Ala Lys Ile Val Pro Lys Ile Ser Tyr Ala Ser 345 350 355 360 aaa gtt aag gaa aac ctc aac aaa act ata cag aac tct tct gtg tca 1218 Lys Val Lys Glu Asn Leu Asn Lys Thr Ile Gln Asn Ser Ser Val Ser 365 370 375 cca act tca tct tca tca tct tca tca tct acc ggg gaa act cag acc 1266 Pro Thr Ser Ser Ser Ser Ser Ser Ser Ser Ser Thr Gly Glu Thr Gln Thr 380 385 390 caa tca tca agt cgc tta tcc cag gtc cct atg tca gcg ctg aaa tct 1314 Gln Ser Ser Ser Arg Leu Ser Gln Val Pro Met Ser Ala Leu Lys Ser 395 400 405 gtt act tct gcc aac ttt tct aat ggg cct gtt tta gca ggg act gat 1362 Val Thr Ser Ala Asn Phe Ser Asn Gly Pro Val Leu Ala Gly Thr Asp 410 415 420 gga aat gtt tat cct cca ggg ggt cag cca ctg cta act act gct gc t 1410 Gly Asn Val Tyr Pro Pro Gly Gly Gln Pro Leu Leu Thr Thr Ala Ala 425 430 435 440 aat act cta aca ccc atc tct tct ggg aca gat tca gtt ctc cag gac 1458 Asn Thr Leu Thr Pro Ile Ser Ser Gly Thr Asp Ser Val Leu Gln Asp 445 450 455 atg agt cta act tca gca gct gtt gaa caa att aag act agc ctt ttt 1506 Met Ser Leu Thr Ser Ala Ala Val Glu Gln Ile Lys Thr Ser Leu Phe 460 465 470 atc tat cct tca aat atg caa act atg ctg ttg agc aca gca caa gtg 1554 Ile Tyr Pro Ser Asn Met Gln Thr Met Leu Leu Ser Thr Ala Gln Val 475 480 485 gat ctg ccc tct cag aca gat cag caa aac ctg ggg gat atc ttc cag 1602 Asp Le Ser Gln Thr Asp Gln Gln Asn Leu Gly Asp Ile Phe Gln 490 495 500 aat cag tgg ggt tta tca ttt ata aat gag ccc agt gct ggc cct gag 1650 Asn Gln Trp Gly Leu Ser Phe Ile Asn Glu Pro Ser Ala Gly Pro Glu 505 510 515 520 act gtt act ggg aag tca tca gag cat aaa gtg atg gag gtg aca ttt 1698 Thr Val Thr Gly Lys Ser Ser Glu His Lys Val Met Glu Val Thr Phe 525 530 535 caa gga gaa tat cct gct act ttg gtt tca cag ggt gct gaa ata att 1746 Gln Gly Glu Tyr Pro Ala Thr Leu Val Ser Gln Gly Ala Glu Ile 540 545 550 ccc tca gga act gag cat cct gtg ttt ccc aag gct tac gag ctg gag 1794 Pro Ser Gly Thr Glu His Pro Val Phe Pro Lys Ala Tyr Glu Leu Glu 555 560 565 aaa aaa cgg act agt cct caa gtt ctg ggt agc att cta aaa tct ggg act 1842 Lys Arg Thr Ser Ser Gl Val Leu Gly Ser Ile Leu Lys Ser Gly Thr 570 575 580 580 act agt gag agt gga gcc tta tcc ttg gaa ccc agt cat ata ggt gac 1890 Thr Ser Glu Ser Gly Ala Leu Ser Leu Glu Pro Ser His Ile Gly Asp 585 590 595 600 600 ctg cag aaa gca gac acc agt agt caa ggt gct tta gtg ttt ctc tca 1938 Leu Gln Lys Ala Asp Thr Ser Ser Gln Gly Ala Leu Val Phe Leu Ser 605 610 615 aag gac tac gag ata gaa agt caa aat cct ctg gcc tct cct acg aac 1986 Lys Asp Tyr Glu Ile Glu Ser Gln Asn Pro Leu Ala Ser Pro Thr Asn 620 625 630 act ttg tta ggc tct gcc aaa gaa cag aga tac cag aga ggc cta gaa 2034 Thr Leu Leu Gly Ser Ala Lys Glu Gln Arg Tyr Gln Arg Gly Leu Glu 635 640 645 645 agg aat gat agc tgg ggt tct ttt gac ctg agg gct gct att gta tat 2082 Arg Asn Asp Ser Trp Gly Ser Phe Asp Leu Arg Ala Ala Ile Val Tyr 650 655 660 cac act aaa gaa atg gaa tct att tgg aat ttg cag aag caa gat ccc 2130 His Lys Glu Met Glu Ser Ile Trp Asn Leu Gln Lys Gln Asp Pro 665 670 675 680 aaa aaa agg ata atc act tac aat gaa gcc atg gat agt cca gat caa tga 2178 Lys Arg Ile Ile Thr Tyr Asn Glu Ala Met Asp Ser Pro Asp Gln 685 690 695 aggaccagac tgcctattcg taacctttct gcagcattag agccatcgtt catgggggac 2238 acaaggcttt tatgctccta gatcttcaac gcagcagagg aaccataagt agaatcacag 2298 gataatatat acaaatatat atatatacat atatatatat atagttattt aaaaaaggca 2358 actgaaagta attagacttc ttaaggaatc aaatttattt caagagacta cacatggtta 2418 tttaatctcc ggtactgaat aggttttttt tcttctgtta gtttttgttt ttaagtgtga 2478 atgcaagtga ttaatgaata cagacttaac aagtgtggtt ctaaagttcc tgctgtcatc 2538 aacttgggca acaaatgacc cactggaaag gcaaatccac ttaaaagatc tctgtatctt 2598 gttctgtgac tgaagtgata cactaatcac ggggaaccca gaatgattca acattttccc 2658 cccactcctc ccttg atctt tttggtttta ctttaattaa gccctgcgag aatgctggat 2718 aaatgccttg aagttagcag ggtgtatttt tttagcgaat atgatttgca tgtcttgcca 2778 ggagttaagc ggcctctggg gtgttgggga aatactttat ttctttccat ttattttttg 2838 tggggcgggg ataggggagg gcattgaagt tctacaattc tggaatagtt agttgatggt 2898 acatagttaa cttggcttcg gttacatatt ggactttaac aactgaagaa tctatgcgtg 2958 tcatttaaag aaaagttgca gaacaagcaa ttggcttaga tatacaatct ggaaaaatat 3018 tcctgtgccc atattttaat gtaattgtat aactgggagc aaaaatatat tctgcttttc 3078 aactgtaggt gctccagact tgctctccgt cactaacact aaatgtgctg ttttccttgt 3138 ttttcatcaa acatttaaga caaacttaga cctttctgta aattatcttt taatttctca 3198 gcaaaatcta aaaggggaag aaaaaagtcc atgaaaacta aaacttttca tgtttttagc 3258 cagtgagaag ataataaacc ctgactgtag aaggtgtgtt ttcatgcaaa ctatacttct 3318 gagcttgtta gcttctaatt atatcttaat aaatatattt tattactag 3367 <210> 20 <211> 695 <212> PRT <213> Homo sapiens <400> 20 Met Glu Glu Lys Pro Gly Gln Pro Gln Pro Gln His His His Ser His 1 5 10 15 His His Pro His His His Pro Gln Gln Gln Gln Gln Gln Pro His His 20 25 30 His His His Tyr Tyr Phe Tyr Asn His Ser His Asn His His His His 35 40 45 His His His Gln Gln Pro His Gln Tyr Leu Gln His Gly Ala Glu Gly 50 55 60 Ser Pro Lys Ala Gln Pro Lys Pro Leu Lys His Glu Gln Lys His Thr 65 70 75 80 Leu Gln Gln His Gln Glu Thr Pro Lys Lys Lys Thr Gly Tyr Gly Glu 85 90 95 Leu Asn Gly Asn Ala Gly Glu Arg Glu Ile Ser Leu Lys Asn Leu Ser 100 105 110 Ser Asp Glu Ala Thr Asn Pro Ile Ser Arg Val Leu Asn Gly Asn Gln 115 120 125 Gln Val Val Asp Thr Ser Leu Lys Gln Thr Val Lys Ala Asn Thr Phe 130 135 140 Gly Lys Ala Gly Ile Lys Thr Lys Asn Phe Ile Gln Lys Asn Ser Met 145 150 155 160 Asp Lys Lys Asn Gly Lys Ser Tyr Glu Asn Lys Ser Gly Glu Asn Gln 165 170 175 Ser Val Asp Lys Ser Asp Thr Ile Pro Ile Pro Asn Gly Val Val Thr 180 185 190 Asn Asn Ser Gly Tyr Ile Thr Asn Gly Tyr Met Ser Lys Gly Ala Asp 195 200 205 Asn Asp Gly Ser Gly Ser Glu Ser Gly Tyr Thr Thr Thr Pro Lys Lys Arg 210 215 220 Lys Ala Arg Arg Asn Ser Ala Lys Gly Cys Glu Asn Leu Asn Ile Val 225 230 235 240 Gln Asp Lys Ile Met Gln Gln Glu Thr Ser Val Pro Thr Leu Lys Gln 245 250 255 Gly Leu Glu Thr Phe Lys Pro Asp Tyr Ser Glu Gln Lys Gly Asn Arg 260 265 270 Val Asp Gly Ser Lys Pro Ile Trp Lys Tyr Glu Thr Gly Pro Gly Gly 275 280 285 285 Thr Ser Arg Gly Lys Pro Ala Val Gly Asp Met Leu Arg Lys Ser Ser 290 295 300 300 Asp Ser Lys Pro Gly Val Ser Ser Lys Lys Phe Asp Asp Arg Pro Lys 305 310 315 320 Gly Lys His Ala Ser Ala Val Ala Ser Lys Glu Asp Ser Trp Thr Leu 325 330 335 Phe Lys Pro Pro Pro Val Phe Pro Val Asp Asn Ser Ser Ala Lys Ile 340 345 350 Val Pro Lys Ile Ser Tyr Ala Ser Lys Val Lys Glu Asn Leu Asn Lys 355 360 365 Thr Ile Gln Asn Ser Ser Val Ser Pro Thr Ser Ser Ser Ser Ser Ser 370 375 380 Ser Ser Thr Gly Glu Thr Gln Thr Gln Ser Ser Ser Arg Leu Ser Gln 385 390 395 400 Val Pro Met Ser Ala Leu Lys Ser Val Thr Ser Ala Asn Phe Ser Asn 405 410 415 Gly Pro ValLeu Ala Gly Thr Asp Gly Asn Val Tyr Pro Pro Gly Gly 420 425 430 Gln Pro Leu Leu Thr Thr Ala Ala Asn Thr Leu Thr Pro Ile Ser Ser 435 440 445 Gly Thr Asp Ser Val Leu Gln Asp Met Ser Leu Thr Ser Ala Ala Val 450 455 460 Glu Gln Ile Lys Thr Ser Leu Phe Ile Tyr Pro Ser Asn Met Gln Thr 465 470 475 480 Met Leu Leu Ser Thr Ala Gln Val Asp Leu Pro Ser Gln Thr Asp Gln 485 490 495 Gln Asn Leu Gly Asp Ile Phe Gln Asn Gln Trp Gly Leu Ser Phe Ile 500 505 510 Asn Glu Pro Ser Ala Gly Pro Glu Thr Val Thr Gly Lys Ser Ser Glu 515 520 525 His Lys Val Met Glu Val Thr Phe Gln Gly Glu Tyr Pro Ala Thr Leu 530 535 540 Val Ser Gln Gly Ala Glu Ile Ile Pro Ser Gly Thr Glu His Pro Val 545 550 555 560 Phe Pro Lys Ala Tyr Glu Leu Glu Lys Arg Thr Ser Pro Gln Val Leu 565 570 575 Gly Ser Ile Leu Lys Ser Gly Thr Thr Ser Glu Ser Gly Ala Leu Ser 580 585 590 Leu Glu Pro Ser His Ile Gly Asp Leu Gln Lys Ala Asp Thr Ser Ser 595 600 605 Gln Gly Ala Leu Val Phe Leu Ser Lys Asp Tyr Glu Ile Glu Ser Gln 610 615 620 Asn Pro Leu Ala Ser Pro Thr Asn Thr Leu Leu Gly Ser Ala Lys Glu 625 630 635 640 Gln Arg Tyr Gln Arg Gly Leu Glu Arg Asn Asp Ser Trp Gly Ser Phe 645 650 655 Asp Leu Arg Ala Ala Ile Val Tyr His Thr Lys Glu Met Glu Ser Ile 660 665 670 Trp Asn Leu Gln Lys Gln Asp Pro Lys Arg Ile Ile Thr Tyr Asn Glu 675 680 685 Ala Met Asp Ser Pro Asp Gln 690 695
【図１】クロ−ンＨＰ１０５５９がコ−ドするヒト蛋白
質と、ヒト仮想蛋白質ＫＩＡＡ０２７６のアミノ酸配列
を比較した図である。FIG. 1 is a diagram comparing the amino acid sequences of human protein encoded by clone HP10559 and human hypothetical protein KIAA0276.
【図２】クロ−ンＨＰ１０５６２がコ−ドするヒト蛋白
質と、ヒト塩基性ロイシンジッパー蛋白質ＬＺＩＰのア
ミノ酸配列を比較した図である。FIG. 2 is a diagram comparing the amino acid sequences of human protein encoded by clone HP10562 and human basic leucine zipper protein LZIP.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ｃ１２Ｎ 1/21 Ｃ１２Ｎ 15/00 ＺＮＡＡ 5/10 5/00 Ａ Ｆターム(参考） 4B024 AA01 AA11 BA01 BA41 BA44 BA61 CA04 DA02 DA06 EA04 GA11 HA01 4B065 AA90X AA93Y AB01 BA02 CA24 CA25 CA44 4H045 AA10 AA11 BA10 BA41 CA40 CA41 DA01 DA75 EA20 EA50 FA74 ──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat ゛ (Reference) C12N 1/21 C12N 15/00 ZNAA 5/10 5/00 A F term (Reference) 4B024 AA01 AA11 BA01 BA41 BA44 BA61 CA04 DA02 DA06 EA04 GA11 HA01 4B065 AA90X AA93Y AB01 BA02 CA24 CA25 CA44 4H045 AA10 AA11 BA10 BA41 CA40 CA41 DA01 DA75 EA20 EA50 FA74
Claims (7)
１４、１６、１８または２０のいずれかのアミノ酸配列
を有する精製ヒト蛋白質。1. SEQ ID NOs: 2, 4, 6, 8, 10, 12,
A purified human protein having the amino acid sequence of any of 14, 16, 18 or 20.
片。2. A DNA fragment encoding the protein of claim 1.
ＮＡであって、１、３、５、７、９、１１、１３、１
５、１７または１９の翻訳領域の塩基配列を有するＤＮ
Ａ断片。3. A human cD encoding the protein of claim 1.
NA, 1, 3, 5, 7, 9, 11, 13, 1
DN having a base sequence of 5, 17, or 19 translation regions
A fragment.
３、１５、１７または１９のいずれかの塩基配列からな
る請求項３のＤＮＡ断片。4. SEQ ID NO: 1, 3, 5, 7, 9, 11, 1
4. The DNA fragment according to claim 3, comprising the base sequence of any one of 3, 15, 17 and 19.
をインビトロ翻訳あるいは宿主細胞内で発現しうる発現
ベクター。5. An expression vector capable of in vitro translation or expression in a host cell of the DNA fragment according to any one of claims 2 to 4.
体であって、請求項１の蛋白質を生産しうる形質転換細
胞。6. A transformant using the expression vector according to claim 5, which is capable of producing the protein according to claim 1.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000035899A JP2001224379A (en) | 2000-02-14 | 2000-02-14 | HUMAN PROTEIN AND cDNA [9] |
| PCT/JP2000/008631 WO2001042302A1 (en) | 1999-12-06 | 2000-12-06 | HUMAN PROTEIN AND cDNA |
| US09/890,688 US20030144475A1 (en) | 1999-12-06 | 2000-12-06 | Human protein and cdna |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000035899A JP2001224379A (en) | 2000-02-14 | 2000-02-14 | HUMAN PROTEIN AND cDNA [9] |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001224379A true JP2001224379A (en) | 2001-08-21 |
Family
ID=18560028
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000035899A Pending JP2001224379A (en) | 1999-12-06 | 2000-02-14 | HUMAN PROTEIN AND cDNA [9] |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2001224379A (en) |
-
2000
- 2000-02-14 JP JP2000035899A patent/JP2001224379A/en active Pending
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