JPH10286089A - Human gene - Google Patents
Human geneInfo
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- JPH10286089A JPH10286089A JP9096908A JP9690897A JPH10286089A JP H10286089 A JPH10286089 A JP H10286089A JP 9096908 A JP9096908 A JP 9096908A JP 9690897 A JP9690897 A JP 9690897A JP H10286089 A JPH10286089 A JP H10286089A
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- Prior art keywords
- leu
- ser
- glu
- arg
- ala
- Prior art date
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、ヒトの疾患の予
防、診断及び治療の指針として有用な遺伝子、より詳し
くはラット、マウス、酵母、線虫、公知のヒト遺伝子等
と類似性を有する新規なヒト遺伝子に関し、該遺伝子の
ｃＤＮＡ解析、染色体へのマッピング及びｃＤＮＡの機
能解析により、該遺伝子を用いた遺伝子診断並びに新し
い治療薬の開発に利用可能な遺伝子に関する。[0001] The present invention relates to a gene useful as a guide for the prevention, diagnosis and treatment of human diseases, and more specifically, to a novel gene having similarity to rat, mouse, yeast, nematode, known human genes and the like. The present invention relates to a gene that can be used for gene diagnosis and development of a new therapeutic drug using the gene by analyzing the cDNA of the gene, mapping it to a chromosome, and analyzing the function of the cDNA.
【０００２】[0002]
【従来の技術】生物の遺伝情報は、細胞の核内に存在す
るＡ、Ｃ、Ｇ及びＴの４種の塩基の並び（ＤＮＡ）とし
て蓄積され、この遺伝情報は個々の生物の系統維持と個
体発生のために保存されている。ヒトの場合、その塩基
数は約３０億（３×１０9）といわれ、その中に５〜１
０万の遺伝子があると推測されている。これらの遺伝情
報は、遺伝子（ＤＮＡ）からｍＲＮＡが転写され、次に
蛋白質に翻訳されるという流れに沿って調節蛋白質、構
造蛋白質、酵素等の創製を通して、生命現象の維持に関
与している。2. Description of the Related Art Genetic information of an organism is accumulated as a sequence (DNA) of four types of bases A, C, G and T existing in the nucleus of a cell. Reserved for ontogeny. In the case of humans, the number of bases is said to be about 3 billion (3 × 10 9 ), of which 5 to 1
It is estimated that there are 10,000 genes. Such genetic information is involved in the maintenance of life phenomena through the creation of regulatory proteins, structural proteins, enzymes, etc. along with the flow of mRNA transcribed from genes (DNA) and then translated into proteins.
【０００３】上記遺伝子から蛋白質翻訳までの流れの異
常は、細胞の増殖・分化等の生命維持システムの異常を
惹起し、各種疾患の原因となるとされている。これまで
の遺伝子解析の結果から、インスリン受容体やＬＤＬ受
容体等の各種受容体、細胞の増殖・分化に係わる例えば
プロテアーゼやＡＴＰａｓｅ、スーパーオキシドディス
ムターゼのような代謝酵素等の遺伝子が、医薬品開発に
とって有用な素材となると考えられた。[0003] Abnormalities in the flow from the above genes to protein translation cause abnormalities in life support systems such as cell proliferation and differentiation, and are thought to cause various diseases. From the results of gene analysis to date, various receptors such as insulin receptor and LDL receptor, and genes related to cell growth and differentiation, such as proteases, ATPase, and metabolic enzymes such as superoxide dismutase, have been identified for drug development. It was thought to be a useful material.
【０００４】しかしながら、ヒト遺伝子の解析や、かか
る解析された遺伝子の機能と各種疾患との係わり等につ
いての研究は、まだ始まったばかりであり、不明な点が
多く、更なる新しい遺伝子の解析、それらの遺伝子の機
能解析及び疾患との係わりの研究、ひいては解析された
遺伝子の利用による遺伝子診断や該遺伝子の医薬用途へ
の応用研究等が当業界で望まれている。[0004] However, the analysis of human genes and the relationship between the functions of the analyzed genes and various diseases has only just begun, and there are many unclear points. There is a need in the art for functional analysis of the gene and research on the relationship with the disease, and further, gene diagnosis using the analyzed gene and research on application of the gene to medical use.
【０００５】[0005]
【発明が解決しようとする課題】上記の如く、新たなヒ
ト遺伝子が提供できれば、各細胞での発現レベルやその
構造及び機能を解析でき、またその発現物の解析等によ
り、之等の関与する疾患、例えば遺伝子病、癌等の病態
解明や診断、治療等が可能となると考えられ、本発明
は、かかる新たなヒトの遺伝子の提供を目的としてい
る。As described above, if a new human gene can be provided, the expression level in each cell, its structure and function can be analyzed, and its expression can be analyzed by analyzing its expression. It is considered that elucidation of pathological conditions, diagnosis, treatment, and the like of diseases, for example, genetic diseases, cancers, and the like, are possible, and the present invention aims to provide such new human genes.
【０００６】[0006]
【課題を解決するための手段】本発明者らは、上記目的
より以下の如く鋭意研究を重ねた。即ち、本発明者ら
は、まずヒト胎児脳、成人血管、胎盤の各種組織より抽
出したｍＲＮＡよりｃＤＮＡを合成し、これをベクター
に組込んでライブラリーを構築し、該ライブラリーでト
ランスフォームした大腸菌コロニーを寒天培地上に形成
させ、該コロニーをランダムにピックアップして９６ウ
ェルマイクロプレートに移し、各種のヒト遺伝子を含む
大腸菌クローンを作製、登録した。次いで、之等の各ク
ローンを培養後、ＤＮＡを抽出精製し、得られるｃＤＮ
Ａを鋳型としてデオキシターミネーター法により４種の
塩基特異的に停止する伸長反応を行ない、自動ＤＮＡシ
ークエンサーにより、登録された各クローンの有するヒ
ト遺伝子の５’末端から約４００塩基配列を決定し、か
くして得られたヒト遺伝子の塩基配列情報より、公知の
バクテリア、酵母、線虫、マウス、ヒト等の各種動植物
種に類似性を有する新規なファミリー遺伝子を検索し
た。尚、上記ｃＤＮＡ解析方法については、本発明者の
ひとりである藤原らの文献に細述されている（藤原
力, 細胞工学, 14,645-654(1995)）。Means for Solving the Problems The present inventors have intensively studied as follows in view of the above objects. That is, the present inventors first synthesized cDNA from mRNA extracted from various tissues of human fetal brain, adult blood vessels, and placenta, incorporated this into a vector to construct a library, and transformed the library. Escherichia coli colonies were formed on an agar medium, and the colonies were randomly picked up and transferred to a 96-well microplate to prepare and register Escherichia coli clones containing various human genes. Next, after culturing each of these clones, the DNA is extracted and purified, and the resulting cDN
Using A as a template, an elongation reaction for terminating the four bases specifically was performed by the deoxyterminator method, and about 400 base sequences were determined from the 5 'end of the human gene of each registered clone by an automatic DNA sequencer. Based on the nucleotide sequence information of the obtained human genes, novel family genes having similarity to various animal and plant species such as known bacteria, yeast, nematodes, mice, and humans were searched. The above-mentioned cDNA analysis method is described in detail in a document by one of the present inventors, Fujiwara et al. (Fujiwara
Force, Cell Engineering, 14 , 645-654 (1995)).
【０００７】その結果、検索されたグループ（レセプタ
ー、ＤＮＡ結合ドメインを有する転写調節因子やシグナ
ル伝達系因子、代謝酵素等）中に、既知の遺伝子と相同
性を有する新規な遺伝子を見い出し、ここに本発明を完
成するに至った。As a result, a novel gene having homology to a known gene was found in the searched group (receptor, transcription regulatory factor having DNA binding domain, signal transduction factor, metabolic enzyme, etc.). The present invention has been completed.
【０００８】即ち、本発明によれば、配列番号：１、：
４、：７、：１０、：１３、：１６及び：１９で示され
るアミノ酸配列をコードする塩基配列を含むことを特徴
とする新規なヒト遺伝子、前記各アミノ酸配列をコード
する配列番号：２、：５、：８、：１１、：１４、：１
７及び：２０で示される塩基配列を含むことを特徴とす
るヒト遺伝子、並びに配列番号：３、：６、：９、：１
２、：１５、：１８及び：２１で示される塩基配列であ
ることを特徴とする新規なヒト遺伝子が提供される。That is, according to the present invention, SEQ ID NO: 1,
A novel human gene comprising a nucleotide sequence encoding an amino acid sequence represented by 4,: 7,: 10,: 13,: 16 and: 19; SEQ ID NO: 2, encoding each amino acid sequence; : 5,: 8,: 11,: 14,: 1
And a human gene comprising the nucleotide sequences of SEQ ID NOs: 7 and: 20, and SEQ ID NOs: 3, 6, 6, 9 and 1
The present invention provides a novel human gene having a nucleotide sequence represented by 2,: 15,: 18 and: 21.
【０００９】以下、本明細書におけるアミノ酸、ペプチ
ド、塩基配列、核酸等の略号による表示は、ＩＵＰＡ
Ｃ、ＩＵＢの規定、「塩基配列又はアミノ酸配列を含む
明細書等の作成のためのガイドライン」（特許庁編）及
び当該分野における慣用記号に従うものとする。Hereinafter, the abbreviations of amino acids, peptides, base sequences, nucleic acids and the like in this specification are referred to as IUPA.
C, IUB rules, "Guidelines for the preparation of specifications containing base sequences or amino acid sequences" (Japan Patent Office), and commonly used symbols in the art.
【００１０】[0010]
【発明の実施の形態】本発明遺伝子の一具体例として
は、後述する実施例１−５に示される「ＧＥＮ−５０２
Ｃ０７」、「ＧＥＮ−５６０Ｄ０６ｌ」、「ＧＥＮ−５
６０Ｄ０６ｓ」、「ＧＥＮ−１２８Ｂ１０」、「ＧＥＮ
−５０６Ｇ１０−ａ」、「ＧＥＮ−５０６Ｇ１０−ｂ」
及び「ＧＥＮ−４２５Ｇ０８」とそれぞれ名付けられた
各クローンの有するＤＮＡ配列から演繹されるものを挙
げることができ、それらの各塩基配列は、配列表に示さ
れる通りである。BEST MODE FOR CARRYING OUT THE INVENTION As a specific example of the gene of the present invention, “GEN-502” described in Example 1-5 described later is used.
C07 "," GEN-560D06l "," GEN-5
60D06s "," GEN-128B10 "," GEN
-506G10-a "," GEN-506G10-b "
And "GEN-425G08", which can be deduced from the DNA sequence of each clone respectively named, and their base sequences are as shown in the sequence listing.
【００１１】これら各クローンの有する遺伝子は、同配
列表に示される各アミノ酸でコードされるヌクレオチド
（核酸）のオープンリーディングフレームを有してお
り、それぞれ後記実施例に示される分子量を有している
と計算された。従って、本明細書においては、以下本発
明に係わる各ヒト遺伝子を、後記実施例１−５に示す名
称にて表示することがある。The genes of these clones have open reading frames of nucleotides (nucleic acids) encoded by the respective amino acids shown in the same sequence listing, and have the molecular weights shown in the Examples below. It was calculated. Therefore, in the present specification, each human gene according to the present invention may be indicated by the name shown in Examples 1-5 below.
【００１２】以下、本発明ヒト遺伝子につき詳述すれ
ば、本発明ヒト遺伝子のそれぞれは、上述した通り、ラ
ット、マウス、酵母、線虫及び他のヒト遺伝子と類似性
を有し、それら類似性ある遺伝子の情報に基づくヒト遺
伝子の解析と、それら解析された遺伝子の機能と各種疾
患との係わりについての研究に利用でき、該遺伝子と関
係ある疾患への遺伝子診断並びに該遺伝子の医薬用途へ
の応用研究に用いることが可能である。即ち、本発明遺
伝子によりコードされる蛋白質（遺伝子産物）の機能
は、既知の相同性遺伝子のそれより類推でき、また本発
明遺伝子の提供によれば、その候補遺伝子を発現ベクタ
ーに組込み、リコンビナントを作製し、酵素活性や結合
活性等の機能を調べることもできる。Hereinafter, the human gene of the present invention will be described in detail. Each of the human genes of the present invention has similarities to rat, mouse, yeast, nematode and other human genes as described above. Analysis of human genes based on information on a certain gene, and use for research on the relationship between the function of the analyzed gene and various diseases, gene diagnosis for diseases related to the gene, and pharmaceutical use of the gene It can be used for applied research. That is, the function of the protein (gene product) encoded by the gene of the present invention can be inferred from that of a known homologous gene, and according to the provision of the gene of the present invention, the candidate gene is incorporated into an expression vector, and the recombinant is used. It can also be prepared and examined for functions such as enzyme activity and binding activity.
【００１３】本発明遺伝子は、例えば配列番号：２で示
されるように、一本鎖ＤＮＡ配列で表されるが、本発明
遺伝子には、かかる一本鎖ＤＮＡ配列に相補的なＤＮＡ
配列や之等の両者を含むコンポーネントもまた包含され
る。尚、配列番号：３ｎ−１（ｎ＝１−７の整数）に示
す本発明遺伝子の配列は、これによりコードされる各ア
ミノ酸残基を示すコドンの一つの組合わせ例であり、本
発明遺伝子はこれに限らず、各アミノ酸残基に対して任
意のコドンを組合わせ選択したＤＮＡ塩基配列を有する
ことも勿論可能である。尚、該コドンの選択は常法に従
うことができ、例えば利用する宿主のコドン使用頻度を
考慮することができる〔Ncl.Acids Res., 9, 43-74 (19
81)〕。The gene of the present invention is represented by a single-stranded DNA sequence, for example, as shown in SEQ ID NO: 2. The gene of the present invention includes a DNA complementary to the single-stranded DNA sequence.
Components that include both arrays and components are also included. The sequence of the gene of the present invention shown in SEQ ID NO: 3n-1 (n is an integer of 1 to 7) is an example of one combination of codons indicating each amino acid residue encoded thereby, and The present invention is not limited to this, and it is of course possible to have a DNA base sequence selected by combining arbitrary codons for each amino acid residue. The selection of the codon can be performed according to a conventional method, for example, considering the codon usage frequency of the host to be used [Ncl. Acids Res., 9 , 43-74 (19
81)].
【００１４】更に本発明遺伝子には、上記で示されるア
ミノ酸配列の一部のアミノ酸乃至アミノ酸配列を置換、
欠失、付加等により改変してなり、同様の機能を有する
同効物をコードするＤＮＡ配列もまた包含される。之等
改変体の製造、改変（変異）等は天然に生じることもあ
り、また翻訳後の修飾により、或は遺伝子工学的手法に
より天然の遺伝子（本発明遺伝子）を、例えばサイトス
ペシフィック・ミュータゲネシス〔Methods in Enzymol
ogy, 154, p350, 367-382 (1987); 同 100, p468 (198
3); Nucleic Acids Research, 12, p9441 (1984); 続生
化学実験講座１「遺伝子研究法II」、日本生化学会編,
p105 (1986)〕等の方法により改変したり、リン酸トリ
エステル法やリン酸アミダイト法等の化学合成手段〔J.
Am. Chem. Soc., 89, p4801 (1967); 同91, p3350 (19
69); Science, 150, p178 (1968); Tetrahedron Lett.,
22, p1859 (1981); 同24, p245 (1983)〕により変異さ
せたＤＮＡを合成したり、それらの組合せにより収得す
ることができる。The gene of the present invention may further comprise a partial amino acid to amino acid sequence substitution of the amino acid sequence shown above,
A DNA sequence which is modified by deletion, addition, etc. and has the same function and encodes the same compound is also included. The production, modification (mutation), etc. of such modified products may occur naturally, and the natural gene (the gene of the present invention) may be prepared by post-translational modification or by genetic engineering techniques, for example, by site-specific mutagenesis. (Methods in Enzymol
ogy, 154 , p350, 367-382 (1987); same 100 , p468 (198
3); Nucleic Acids Research, 12 , p9441 (1984);
p105 (1986)] or chemical synthesis means such as the phosphate triester method and the phosphate amidite method (J.
Am. Chem. Soc., 89 , p4801 (1967); id. 91 , p3350 (19
69); Science, 150 , p178 (1968); Tetrahedron Lett.,
22 , p1859 (1981); ibid., 24 , p245 (1983)], and can be obtained by a combination thereof.
【００１５】本発明遺伝子は、これを利用して、即ち例
えばこれを微生物のベクターに組込み、形質転換された
微生物を培養することによって、上記各遺伝子でコード
される蛋白を容易にかつ安定して発現できる。By utilizing the gene of the present invention, that is, for example, by incorporating the gene into a microorganism vector and culturing the transformed microorganism, the protein encoded by each of the above genes can be easily and stably obtained. Can be expressed.
【００１６】また本発明の遺伝子を利用して得られる各
蛋白は、之等を用いて、特異抗体を作成することもでき
る。ここで抗原として用いられるコンポーネントは、上
記遺伝子工学的手法に従って大量に産生される蛋白を用
いることができ、得られる抗体はポリクローナル抗体及
びモノクローナル抗体のいずれでもよく、之等抗体はそ
れぞれの蛋白の精製、測定、識別等に有利に利用でき
る。Each protein obtained by using the gene of the present invention can be used to prepare a specific antibody. As the component used as the antigen, a protein produced in large amounts according to the above-mentioned genetic engineering technique can be used, and the obtained antibody may be either a polyclonal antibody or a monoclonal antibody. , Measurement, identification and the like.
【００１７】本発明遺伝子の製造は、本発明によって開
示された本発明遺伝子についての配列情報によれば、一
般的遺伝子工学的手法により容易に実施できる〔Molecu
larCloning 2nd Ed, Cold Spring Harbor Laboratory P
ress (1989)；続生化学実験講座「遺伝子研究法Ｉ、I
I、III」、日本生化学会編 (1986)等参照〕。The production of the gene of the present invention can be easily carried out by general genetic engineering techniques based on the sequence information on the gene of the present invention disclosed by the present invention [Molecu
larCloning 2nd Ed, Cold Spring Harbor Laboratory P
ress (1989);
I, III ", edited by The Biochemical Society of Japan (1986)].
【００１８】これは例えばヒトｃＤＮＡライブラリー
（各遺伝子の発現される適当な起源細胞より常法に従い
調製されたもの）から、本発明遺伝子に特有の適当なプ
ローブや抗体を用いて所望クローンを選択することによ
り実施できる〔Proc. Natl. Acad. Sci. USA., 78, 661
3 (1981); Science, 222, 778 (1983)等〕。The desired clone is selected from, for example, a human cDNA library (prepared from an appropriate source cell in which each gene is expressed) using an appropriate probe or antibody specific to the gene of the present invention. Natl. Acad. Sci. USA., 78 , 661.
3 (1981); Science, 222 , 778 (1983), etc.].
【００１９】上記方法において、起源細胞としては、目
的の遺伝子を発現する各種の細胞、組織や之等に由来す
る培養細胞等が例示され、これからの全ＲＮＡの分離、
ｍＲＮＡの分離や精製、ｃＤＮＡへの変換（合成）とそ
のクローニング等はいずれも常法に従い実施できる。ま
た、ｃＤＮＡライブラリーは市販されてもおり、本発明
においてはそれらｃＤＮＡライブラリー、例えばクロー
ンテック社（ClontechLab. Inc.）より市販の各種ｃＤ
ＮＡライブラリー等を用いることもできる。In the above method, examples of the source cell include various cells expressing the target gene, cultured cells derived from tissues and the like, and the separation of total RNA therefrom.
Isolation and purification of mRNA, conversion to cDNA (synthesis), cloning thereof, and the like can all be carried out according to conventional methods. In addition, cDNA libraries are also commercially available. In the present invention, these cDNA libraries, for example, various cDNAs available from ClontechLab. Inc.
An NA library or the like can also be used.
【００２０】ｃＤＮＡライブラリーからの本発明遺伝子
のスクリーニングは、前記通常の方法に従い実施するこ
とができる。該スクリーニング方法としては、例えばｃ
ＤＮＡの産生する蛋白質に対して、該蛋白質特異抗体を
使用した免疫的スクリーニングにより、対応するｃＤＮ
Ａクローンを選択する方法、目的のＤＮＡ配列に選択的
に結合するプローブを用いたプラークハイブリダイゼー
ション、コロニーハイブリダイゼーション等や之等の組
合せを例示できる。ここで用いられるプローブとして
は、本発明遺伝子のＤＮＡ配列に関する情報をもとにし
て化学合成されたＤＮＡ配列等を用いるのが一般的であ
り、勿論既に取得された本発明遺伝子やその断片もかか
るプローブとして利用できる。The screening of the gene of the present invention from the cDNA library can be carried out according to the above-mentioned usual method. The screening method includes, for example, c
By performing an immunoscreening on a protein produced by DNA using the protein-specific antibody, the corresponding cDN
Examples of the method include selecting a clone A, plaque hybridization using a probe that selectively binds to a target DNA sequence, colony hybridization, and combinations thereof. As the probe used here, a DNA sequence or the like chemically synthesized based on information on the DNA sequence of the gene of the present invention is generally used. Of course, the gene of the present invention or a fragment thereof which has already been obtained is also used. Can be used as a probe.
【００２１】更に各細胞、組織より抽出、単離精製され
た天然抽出物の部分アミノ酸配列情報に基づき、センス
・プライマー、アンチセンス・プライマーをスクリーニ
ング用プローブとして用いることもできる。Further, based on partial amino acid sequence information of a natural extract extracted, isolated and purified from each cell or tissue, sense primers and antisense primers can be used as screening probes.
【００２２】また、本発明遺伝子の取得に際しては、Ｐ
ＣＲ法〔Science, 230, 1350-1354(1985)〕によるＤＮ
Ａ／ＲＮＡ増幅法が好適に利用できる。殊にライブラリ
ーから全長のｃＤＮＡが得られ難いような場合に、レー
ス法（ＲＡＣＥ：Rapid amplification of cDNA ends；
実験医学、12(6), 35-38 (1994)）、殊に５′−レース
（５′−ＲＡＣＥ）法〔Frohman,M.A., et al., Proc.N
atl.Acad.Sci., USA.,8, 8998-9002 (1988)〕の採用が
好適である。かかるＰＣＲ法の採用に際して使用される
プライマーは、既に本発明によって明らかにされた本発
明遺伝子の配列情報に基づいて適宜設定することがで
き、これは常法に従い合成することができる。When obtaining the gene of the present invention,
DN by CR method [Science, 230 , 1350-1354 (1985)]
The A / RNA amplification method can be suitably used. Particularly, when it is difficult to obtain a full-length cDNA from the library, the lace method (RACE: Rapid amplification of cDNA ends;
Experimental Medicine, 12 (6), 35-38 (1994)), especially the 5'-RACE method [Frohman, MA, et al., Proc.
Atl. Acad. Sci., USA., 8 , 8998-9002 (1988)] is preferred. Primers to be used when employing such a PCR method can be appropriately set based on the sequence information of the gene of the present invention which has already been revealed by the present invention, and can be synthesized according to a conventional method.
【００２３】尚、増幅させたＤＮＡ／ＲＮＡ断片の単離
精製は、前記の通り常法に従うことができ、例えばゲル
電気泳動法等によればよい。The isolation and purification of the amplified DNA / RNA fragment can be carried out by a conventional method as described above, for example, by gel electrophoresis.
【００２４】上記で得られる本発明遺伝子或は各種ＤＮ
Ａ断片等の塩基配列の決定も、常法に従うことができ、
例えばジデオキシ法〔Proc. Natl. Acad. Sci. USA., 7
4, 5463-5467 (1977)〕やマキサム−ギルバート法〔Met
hod in Enzymology, 65, 499(1980)〕等により行なうこ
とができる。かかる塩基配列の決定は、市販のシークエ
ンスキット等を用いても容易に行ない得る。The gene of the present invention or various DNs obtained above
The determination of the base sequence of the A fragment and the like can be performed according to a conventional method,
For example, the dideoxy method [Proc. Natl. Acad. Sci. USA., 7
4 , 5463-5467 (1977)) or the Maxam-Gilbert method (Met
hod in Enzymology, 65 , 499 (1980)]. Such determination of the nucleotide sequence can be easily performed even using a commercially available sequence kit or the like.
【００２５】本発明遺伝子の利用によれば、通常の遺伝
子組換え技術〔例えば、Science, 224, p1431 (1984);
Biochem. Biophys. Res. Comm., 130, p692 (1985); Pr
oc.Natl. Acad. Sci., USA., 80, p5990 (1983)及び前
記引用文献等参照〕に従うことにより各組換え体蛋白を
得ることができる。該蛋白の製造は、より詳細には、本
発明遺伝子が宿主細胞中で発現できる組換えＤＮＡを作
成し、これを宿主細胞に導入して形質転換し、該形質転
換体を培養することにより行なわれる。According to the use of the gene of the present invention, conventional gene recombination techniques [for example, Science, 224 , p1431 (1984);
Biochem. Biophys. Res. Comm., 130 , p692 (1985); Pr
oc. Natl. Acad. Sci., USA, 80 , p5990 (1983) and the above-cited references] can be used to obtain each recombinant protein. More specifically, the production of the protein is carried out by preparing a recombinant DNA capable of expressing the gene of the present invention in a host cell, introducing it into a host cell, transforming the same, and culturing the transformant. It is.
【００２６】ここで宿主細胞としては、真核生物及び原
核生物のいずれも用いることができる。該真核生物の細
胞には、脊椎動物、酵母等の細胞が含まれ、脊椎動物細
胞としては、例えばサルの細胞であるＣＯＳ細胞〔Cel
l, 23, 175-182 (1981)〕やチャイニーズ・ハムスター
卵巣細胞及びそのジヒドロ葉酸レダクターゼ欠損株〔Pr
oc. Natl. Acad. Sci., USA., 77, 4216-4220 (1980)〕
等がよく用いられているが、之等に限定される訳ではな
い。脊椎動物の発現ベクターとしては、通常発現しよう
とする遺伝子の上流に位置するプロモーター、ＲＮＡの
スプライス部位、ポリアデニル化部位及び転写終了配列
等を保有するものを使用でき、これは更に必要により複
製起点を有していてもよい。該発現ベクターの例として
は、例えば、ＳＶ４０の初期プロモーターを保有するｐ
ＳＶ２dhfr〔Mol. Cell. Biol., 1, 854 (1981)〕等を
例示できる。また、真核微生物としては、酵母が一般に
よく用いられ、中でもサッカロミセス属酵母を有利に利
用できる。該酵母等の真核微生物の発現ベクターとして
は、例えば酸性ホスフアターゼ遺伝子に対するプロモー
ターを有するｐＡＭ８２〔Proc. Natl. Acad. Sci., US
A., 80, 1-5 (1983)〕等を利用できる。As the host cell, any of eukaryotes and prokaryotes can be used. The eukaryotic cells include cells such as vertebrates and yeast, and the vertebrate cells include, for example, COS cells [Cel cells]
l, 23 , 175-182 (1981)) and Chinese hamster ovary cells and their dihydrofolate reductase-deficient strains (Pr
oc. Natl. Acad. Sci., USA., 77 , 4216-4220 (1980)]
Are often used, but are not limited to these. As a vertebrate expression vector, a vector having a promoter, an RNA splice site, a polyadenylation site, a transcription termination sequence, and the like, which is usually located upstream of the gene to be expressed, can be used. You may have. Examples of such expression vectors include, for example, p40 carrying the early promoter of SV40.
SV2 dhfr [Mol. Cell. Biol., 1 , 854 (1981)] and the like. As eukaryotic microorganisms, yeasts are generally used, and among them, yeasts belonging to the genus Saccharomyces can be advantageously used. Examples of expression vectors for eukaryotic microorganisms such as the yeast include pAM82 having a promoter for the acid phosphatase gene [Proc. Natl. Acad. Sci., US
A., 80 , 1-5 (1983)].
【００２７】また、本発明遺伝子の発現ベクターとして
は、原核生物遺伝子融合ベクターを好ましく利用するこ
とができ、該ベクターの具体例としては、例えば分子量
２６０００のＧＳＴドメイン（S. japonic um 由来）を
有するｐＧＥＸ−２ＴＫやｐＧＥＸ−４Ｔ−２等を例示
することができる。[0027] As the expression vector of the gene of the present invention, prokaryotic gene fusion vectors can be favorably utilized as a specific example of the vector has, for example, GST domain with a molecular weight of 26000 (S. japonic um derived) Examples include pGEX-2TK and pGEX-4T-2.
【００２８】原核生物の宿主としては、大腸菌や枯草菌
が一般によく用いられる。之等を宿主とする場合、例え
ば該宿主菌中で複製可能なプラスミドベクターを用い、
このベクター中に本発明遺伝子が発現できるように該遺
伝子の上流にプロモーター及びＳＤ（シヤイン・アンド
・ダルガーノ）塩基配列、更に蛋白合成開始に必要な開
始コドン（例えばＡＴＧ）を付与した発現プラスミドを
利用するのが好ましい。上記宿主としての大腸菌として
は、エシエリヒア・コリ（Escherichia coli）Ｋ１２株
等がよく用いられ、ベクターとしては一般にｐＢＲ３２
２及びその改良ベクターがよく用いられるが、之等に限
定されず公知の各種の菌株及びベクターをも利用でき
る。プロモーターとしては、例えばトリプトファン（tr
p） プロモーター、lpp プロモーター、lac プロモータ
ー、PL/PR プロモーター等を使用できる。Escherichia coli and Bacillus subtilis are commonly used as prokaryotic hosts. When these are used as a host, for example, using a plasmid vector that is replicable in the host bacterium,
In order to express the gene of the present invention in this vector, an expression plasmid having a promoter and an SD (Shine and Dalgarno) base sequence upstream of the gene and an initiation codon (eg, ATG) necessary for initiation of protein synthesis is used. Is preferred. Escherichia coli K12 strain or the like is often used as Escherichia coli as the host, and the vector is generally pBR32
2 and its improved vector are often used, but not limited thereto, and various known strains and vectors can also be used. As a promoter, for example, tryptophan (tr
p) Promoters, lpp promoters, lac promoters, PL / PR promoters and the like can be used.
【００２９】かくして得られる所望の組換えＤＮＡの宿
主細胞への導入方法及びこれによる形質転換方法として
は、一般的な各種方法を採用できる。また得られる形質
転換体は、常法に従い培養でき、該培養により本発明遺
伝子によりコードされる目的の蛋白が生産、発現され
る。該培養に用いられる培地としては、採用した宿主細
胞に応じて慣用される各種のものを適宜選択利用でき、
その培養も宿主細胞の生育に適した条件下で実施でき
る。As a method for introducing the desired recombinant DNA thus obtained into a host cell and a transformation method using the same, various general methods can be employed. The obtained transformant can be cultured according to a conventional method, and the target protein encoded by the gene of the present invention is produced and expressed by the culture. As the medium used for the culture, various types commonly used depending on the host cell employed can be appropriately selected and used,
The culture can also be performed under conditions suitable for the growth of the host cell.
【００３０】上記により、形質転換体の細胞内、細胞外
乃至は細胞膜上に目的とする組換え蛋白が発現、生産、
蓄積乃至分泌される。As described above, the desired recombinant protein can be expressed, produced, or expressed inside or outside the cell of the transformant or on the cell membrane.
It is accumulated or secreted.
【００３１】各組換え蛋白は、所望により、その物理的
性質、化学的性質等を利用した各種の分離操作〔「生化
学データーブックII」、1175-1259頁、第１版第１刷、1
980年 6月23日株式会社東京化学同人発行；Biochemistr
y, 25(25), 8274-8277 (1986); Eur. J. Biochem., 16
3, 313-321 (1987) 等参照〕により分離、精製できる。
該方法としては、具体的には例えば通常の再構成処理、
蛋白沈澱剤による処理（塩析法）、遠心分離、浸透圧シ
ョック法、超音波破砕、限外濾過、分子篩クロマトグラ
フィー（ゲル濾過）、吸着クロマトグラフィー、イオン
交換クロマトグラフィー、アフィニティクロマトグラフ
ィー、高速液体クロマトグラフィー（ＨＰＬＣ）等の各
種液体クロマトグラフィー、透析法、之等の組合せ等を
例示でき、特に好ましい上記方法としては所望の蛋白を
結合させたカラムを利用したアフィニティクロマトグラ
フィーを例示できる。Each of the recombinant proteins may be subjected to various separation operations utilizing its physical properties, chemical properties, etc. [Biochemical Data Book II, pages 1175-1259, 1st edition, 1st print, 1st edition, if desired.
June 23, 980 Published by Tokyo Chemical Co., Ltd .; Biochemistr
y, 25 (25), 8274-8277 (1986); Eur. J. Biochem., 16
3 , 313-321 (1987), etc.].
As the method, specifically, for example, a normal reconstruction process,
Treatment with protein precipitant (salting out method), centrifugation, osmotic shock method, sonication, ultrafiltration, molecular sieve chromatography (gel filtration), adsorption chromatography, ion exchange chromatography, affinity chromatography, high-performance liquid Examples thereof include various liquid chromatography such as chromatography (HPLC), dialysis, combinations thereof, and the like. Particularly preferred examples of the above method include affinity chromatography using a column to which a desired protein is bound.
【００３２】また、本発明によって明らかにされた本発
明遺伝子の配列情報を基にすれば、例えば該遺伝子の一
部又は全部の塩基配列を利用することにより、各種ヒト
組織における本発明遺伝子の発現の検出を行なうことが
できる。これは常法に従って行なうことができ、例えば
ＲＴ−ＰＣＲ（Reverse transcribed-Polymerase chain
reaction）（Kawasaki, E.S., et al., Amplification
of RNA. In PCR Protocol, A Guide to methods and a
pplications, Academic Press, Inc., SanDiego, 21-27
(1991)〕によるＲＮＡ増幅により、またノーザンブロッ
ティング解析〔Molecular Cloning, Cold Spring Harbo
r Laboratory(1989)〕等により、いずれも良好に実施し
得る。Further, based on the sequence information of the gene of the present invention revealed by the present invention, the expression of the gene of the present invention in various human tissues can be carried out, for example, by utilizing a partial or entire nucleotide sequence of the gene. Can be detected. This can be performed according to a conventional method, for example, RT-PCR (Reverse transcribed-Polymerase chain).
reaction) (Kawasaki, ES, et al., Amplification
of RNA.In PCR Protocol, A Guide to methods and a
pplications, Academic Press, Inc., SanDiego, 21-27
(1991)], and Northern blotting analysis [Molecular Cloning, Cold Spring Harbo
r Laboratory (1989)].
【００３３】尚、前記ＰＣＲ法を採用する場合におい
て、用いられるプライマーは、本発明遺伝子のみを特異
的に増幅できる本発明遺伝子に特有のものである限り何
等限定はなく、本発明遺伝情報に基いてその配列を適宜
設定することができる。通常これは常法に従って２０〜
３０ヌクレオチド程度の部分配列を有するものとするこ
とができる。その好適な例は、後記実施例１−５に示す
通りである。When the PCR method is employed, the primers used are not particularly limited as long as they are specific to the gene of the present invention capable of specifically amplifying only the gene of the present invention. Thus, the arrangement can be appropriately set. Usually this is 20-
It may have a partial sequence of about 30 nucleotides. Preferred examples thereof are as shown in Examples 1-5 described below.
【００３４】しかして、本発明はかかる新規なヒト遺伝
子に特有の検出に有用なプライマー及び／又はプローブ
をも提供するものである。Thus, the present invention also provides primers and / or probes useful for detection unique to such a novel human gene.
【００３５】[0035]
【発明の効果】本発明によれば、新規なヒト遺伝子が提
供され、該遺伝子を用いれば、該遺伝子の各種組織での
発現の検出や、その構造及び機能を解析でき、また、該
遺伝子でコードされるヒト蛋白の遺伝子工学的製造が可
能となり、これらにより、その発現物の解析等により、
之等の関与する疾患、例えば遺伝子病、癌等の病態解明
や診断、治療等が可能となる。According to the present invention, a novel human gene is provided, and by using the gene, the expression of the gene in various tissues can be detected, and its structure and function can be analyzed. Genetically engineered production of the encoded human protein becomes possible.
This makes it possible to elucidate, diagnose, and treat diseases associated with the disease, such as genetic diseases and cancer.
【００３６】[0036]
【実施例】以下、本発明を更に詳しく説明するため、実
施例を挙げる。The present invention will now be described in further detail with reference to examples.
【００３７】[0037]
【実施例１】ヒトｒａｂ７ＧＴＰ結合類似タンパク遺伝
子 （１）ヒトｒａｂ７ＧＴＰ結合類似タンパク遺伝子のク
ローニング及びＤＮＡシークエンシング ヒト胎児脳、成人血管、胎盤の各組織より抽出したｍＲ
ＮＡをクローンテック社より購入して出発材料とした。
上記ｍＲＮＡよりｃＤＮＡを合成し、ベクターλＺＡＰ
II（ストラタジーン社製）に挿入し、ｃＤＮＡライブラ
リーを構築した（大塚ＧＥＮリサーチ・インスティチュ
ート、大塚製薬株式会社）。インビボ・エキシジョン法
（in vivo excision: Short, J. M., et al., Nucleic
Acids Res., 16, 7583-7600 (1988)）によって寒天培地
上にヒト遺伝子を含む大腸菌コロニーを形成させ、ラン
ダムにそのコロニーをピックアップし、９６ウエルマイ
クロプレートにヒト遺伝子を含む大腸菌クローンを登録
した。登録されたクローンは、−８０℃にて保存した。Example 1 Human rab7GTP-binding similar protein gene (1) Cloning and DNA sequencing of human rab7GTP-binding similar protein gene mR extracted from human fetal brain, adult blood vessels, and placenta
NA was purchased from Clonetech and used as starting material.
CDNA is synthesized from the above mRNA, and the vector λZAP
II (Stratagene) to construct a cDNA library (Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd.). In vivo excision: Short, JM, et al., Nucleic
Acids Res., 16 , 7583-7600 (1988)), an E. coli colony containing a human gene was formed on an agar medium, the colony was randomly picked up, and an E. coli clone containing a human gene was registered in a 96-well microplate. . The registered clone was stored at -80 ° C.
【００３８】次に登録した各クローンを１．５ｍｌのＬ
Ｂ培地で一昼夜培養し、プラスミド自動抽出装置ＰＩ−
１００（クラボウ社製）を用いてＤＮＡを抽出精製し
た。尚、コンタミした大腸菌のＲＮＡは、ＲＮase処理
により分解除去した。最終的に３０μｌに溶解し、２μ
ｌはミニゲルによりおおまかにＤＮＡのサイズ及び量を
チェックした。その７μｌをシークエンス反応用に用
い、残りの２１μｌは、プラスミドＤＮＡとして４℃に
保存した。また、この方法は若干のプログラム変更によ
って後記実施例で示されるＦＩＳＨ（fluoresence in s
itu hybridization）のプローブ用としても使用可能な
コスミドを抽出することができる。Next, each of the registered clones was placed in 1.5 ml of L
Culture in B medium all day and night, automatic plasmid extractor PI-
DNA was extracted and purified using 100 (manufactured by Kurabo Industries, Ltd.). The contaminated RNA of Escherichia coli was decomposed and removed by RNase treatment. Finally, dissolve in 30 μl and add 2 μl
For l, the size and amount of DNA were roughly checked by minigel. 7 μl thereof was used for a sequencing reaction, and the remaining 21 μl was stored at 4 ° C. as plasmid DNA. In addition, this method can be applied to FISH (fluoresence in ss
Cosmids that can also be used as probes for itu hybridization) can be extracted.
【００３９】続いてＴ３、Ｔ７、或は合成オリゴヌクレ
オチド・プライマーを用いるサンガーらのジデオキシタ
ーミネーター法（Sanger, F., et al., Proc. Natl. A
cad.Sci., U.S.A., 74, 5463-5467 (1977)）或はジデオ
キシターミネーター法にＰＣＲ法を加味した方法である
サイクルシークエンス法（Carothers, A.M., et al., B
io. Techniques, 7, 494-499 (1989)）を実施した。之
等の方法は少量のプラスミドＤＮＡ（およそ０．１−
０．５μｇ）をテンプレート（鋳型）として４種の塩基
を特異的に停止する伸長反応させる方法である。Subsequently, the dideoxy terminator method of Sanger et al. Using T3, T7 or synthetic oligonucleotide primers (Sanger, F., et al., Proc. Natl. A
cad. Sci., USA, 74 , 5463-5467 (1977)) or a cycle sequence method (Carothers, AM, et al., B) which is a method in which the PCR method is added to the dideoxy terminator method.
io. Techniques, 7 , 494-499 (1989)). These methods use a small amount of plasmid DNA (approximately 0.1-
0.5 μg) as a template (template) to carry out an elongation reaction to specifically stop four kinds of bases.
【００４０】シークエンスプライマーとして、ＦＩＴＣ
（fluorescein isothiocyanate）蛍光標識したものを使
用し、Ｔａｑポリメラーゼにより約２５サイクル反応さ
せた。蛍光標識したＤＮＡ断片につき、自動ＤＮＡシー
クエンサー、ＡＬＦTMＤＮＡシークエンサー（ファルマ
シア社製）によりｃＤＮＡの５’末端側から約４００塩
基の配列を決定した。FITC was used as a sequencing primer.
(Fluorescein isothiocyanate) Fluorescein-labeled one was used and reacted for about 25 cycles with Taq polymerase. For the fluorescently labeled DNA fragment, a sequence of about 400 bases from the 5 ′ end of the cDNA was determined by an automatic DNA sequencer, ALF ™ DNA sequencer (Pharmacia).
【００４１】３’非翻訳領域は、各遺伝子の異質性（he
terogeneity）が高く、個々の遺伝子を区別するのに適
しているので、場合によっては、３’側のシークエンス
も行なった。[0041] The 3 'untranslated region corresponds to the heterogeneity of each gene (he
In some cases, 3′-sequencing was also performed due to high terogeneity and suitable for distinguishing individual genes.
【００４２】ＤＮＡシークエンサーで得られた膨大な塩
基配列情報を、６４ビットのコンピューターＤＥＣ３４
００に転送し、コンピュターによるホモロジー解析を行
なった。該ホモロジー解析は、ＵＷＧＣＧのＦＡＳＴＡ
プログラム（Pearson, W.R.and Lipman, D. J., Proc.N
atl.Acad.Sci., USA., 85, 2444-2448 (1988)）による
データーベース（GenBank, EMBL）検索により行なっ
た。The vast amount of base sequence information obtained by the DNA sequencer is converted to a 64-bit computer DEC34.
00 and transferred to a computer for homology analysis. The homology analysis was performed using FAWG of UWGCG.
Programs (Pearson, WRand Lipman, DJ, Proc.N
Atl. Acad. Sci., USA., 85 , 2444-2448 (1988)) and a database (GenBank, EMBL) search.
【００４３】ヒト胎児脳ｃＤＮＡライブラリーについて
の上記解析方法は、藤原ら〔Fujiwara, T., et al., DN
A Res., 2, 107-111 (1991)〕に詳述されている。The above analysis method for the human fetal brain cDNA library is described by Fujiwara et al. [Fujiwara, T., et al., DN.
A Res., 2 , 107-111 (1991)].
【００４４】上記と同様な方法で、構築されたヒト胎盤
ｃＤＮＡライブラリーから無作為に選択したおよそ５０
４０のＥＳＴｓ（expressed sequence tags:発現遺伝子
断片の部分ＤＮＡ配列）の配列決定を実施した。In the same manner as described above, approximately 50 randomly selected human human placenta cDNA libraries were constructed.
Forty ESTs (expressed sequence tags: partial DNA sequences of expressed gene fragments) were sequenced.
【００４５】ＦＡＳＴＡプログラムによるGene Bankと
ＥＭＢＬの配列検索の中で、ＧＥＮ−５０２Ｃ０７と命
名したクローンが、ラットのｒａｂ７ＧＴＰ結合タンパ
ク（accession no. X96663）に対して、最も強く相同性
を示すことを発見した。In a sequence search of Gene Bank and EMBL by the FASTA program, it was found that a clone named GEN-502C07 showed the strongest homology to rat rab7 GTP-binding protein (accession no. X96663). did.
【００４６】テンプレート（鋳型）としてベクター（pB
luescript vector: ストラタジーン社製（Stratagen
e)）内に挿入された二本鎖ＤＮＡと、プライマーとして
の合成オリゴヌクレオチドとを使用して、サンガーらの
ジデオキシ・チェーン・ターミネェーション法によっ
て、全コード領域を含むｃＤＮＡの塩基配列を決定し、
他のいくつかのｒａｂ関連遺伝子のＤＮＡ配列と比較し
た。A vector (pB
luescript vector: manufactured by Stratagene (Stratagen
e) The nucleotide sequence of the cDNA containing the entire coding region is determined by the dideoxy chain termination method of Sanger et al., using the double-stranded DNA inserted in (1) and a synthetic oligonucleotide as a primer. And
The DNA sequence of several other rab-related genes was compared.
【００４７】本発明遺伝子に関連するシグナル伝達分子
のＲａｓ関連ファミリーのメンバーであるＲａｂタンパ
クは、真核細胞内に存在するＧＴＰに結合する低分子タ
ンパクである。このタンパクは、エキソサイトーシス系
とエンドサイトーシス系の両経路の制御に重要な役割を
担っており、既に３０種以上のＲａｂ関連タンパク質が
報告されている。それらはＧＴＰ／ＧＤＰ結合とＧＴＰ
加水分解能に対する領域において、Ｒａｓタンパクと相
同性を有している。多くのＲａｂタンパクは全ての細胞
に存在し、膜輸送の機能を有する。しかしながら、いく
つかのＲａｂタンパクは組織特異性を示す。例えばＲａ
ｂ３ａは神経末端で神経伝達物質の遊離の調節に関与す
ることが提唱され、脳に特異的発現が見られている〔Fi
scher von Mollard, G., et al., Nature, 349, 79-81
(1991)〕。更に、脂肪細胞においてＲａｂ３ｄ〔Baldin
i, G., et al., Proc. Natl. Acad. Sci., U.S.A., 89,
5049-5052 (1992)〕の、また上皮細胞においてＲａｂ
１７〔Lutcke, A., et al.,J. Cell Biol., 121, 553-5
64 (1993)〕の、特異的発現もそれぞれ報告されてい
る。Rab protein, a member of the Ras-related family of signaling molecules related to the gene of the present invention, is a small protein that binds to GTP present in eukaryotic cells. This protein plays an important role in controlling both exocytosis and endocytosis pathways, and 30 or more Rab-related proteins have already been reported. They are GTP / GDP binding and GTP
It has homology to Ras protein in the region for hydrolytic resolution. Many Rab proteins are present in all cells and have a function of membrane transport. However, some Rab proteins show tissue specificity. For example, Ra
b3a has been proposed to be involved in the regulation of neurotransmitter release at nerve endings, and specific expression has been observed in the brain [Fi
scher von Mollard, G., et al., Nature, 349 , 79-81
(1991)]. Furthermore, Rab3d [Baldin
i, G., et al., Proc. Natl. Acad. Sci., USA, 89 ,
5049-5052 (1992)] and Rab in epithelial cells.
17 [Lutcke, A., et al., J. Cell Biol., 121 , 553-5
64 (1993)].
【００４８】配列番号：３に、上記ＧＥＮ−５０２Ｃ０
７と命名されたｃＤＮＡクローンの核酸配列を、配列番
号：２に、そのクローンのコーディング領域の核酸配列
を、また配列番号：１に、該核酸配列でコードされる推
定アミノ酸配列を、それぞれ示す。SEQ ID NO: 3 shows that the above-mentioned GEN-502C0
The nucleic acid sequence of the cDNA clone designated as No. 7 is shown in SEQ ID NO: 2, the nucleic acid sequence of the coding region of the clone, and SEQ ID NO: 1 shows the deduced amino acid sequence encoded by the nucleic acid sequence.
【００４９】このｃＤＮＡは、２４４３塩基からなり、
２０３アミノ酸をコードする６０９塩基のオープン・リ
ーディング・フレームを含んでいた。上記核酸配列に
は、翻訳開始部位と思われる（Kozak, M., J. Biol. Ch
em., 266, 19867-19870 (1991)）配列、即ち（Ａ／Ｇ）
ＣＣＡＴＧＧ配列が、その３８−４４番目の核酸残基の
位置に認められ、また３’非翻訳領域にはＡｌｕ配列が
含まれていた。This cDNA consists of 2443 bases,
It contained an open reading frame of 609 bases encoding 203 amino acids. The above nucleic acid sequence appears to be a translation initiation site (Kozak, M., J. Biol. Ch.
em., 266 , 19867-19870 (1991)) sequence, that is, (A / G)
The CCATGG sequence was found at position 38-44 of the nucleic acid residue, and the 3 'untranslated region contained an Alu sequence.
【００５０】また、このｃＤＮＡは、翻訳領域におい
て、ラットｒａｂＧＴＰ結合類似タンパク（X96663）と
８９％相同性を示した。In addition, this cDNA showed 89% homology with the rat rabGTP-binding similar protein (X96663) in the translation region.
【００５１】本発明遺伝子でコードされる推定アミノ酸
配列と、ラットＲａｂＧＴＰ結合タンパク（X96663）と
は、９４％同一性を示した。更に、１８６アミノ酸にお
いてＲａｂ関連ＧＴＰ結合タンパク（M94043）と５５
％、Ｒａｂ７結合タンパクとは１７８アミノ酸領域に亘
り３５％の同一性を示した。The deduced amino acid sequence encoded by the gene of the present invention showed 94% identity with rat Rab GTP binding protein (X96663). Furthermore, at 186 amino acids, Rab-related GTP-binding protein (M94043) and 55
%, 35% identity over the 178 amino acid region with the Rab7 binding protein.
【００５２】本遺伝子産物の推定されたアミノ酸配列
は、ＲａｓタンパクにおけるＧＴＰ結合に重要な部位と
同様に、４つの保存された領域（Pai, E. F., et al.,
Nature, 341, 209-214 (1989): Valencia, A., et al.,
Biochemistry, 30, 4637-4648(1991)）を有していた
が、２つのモチーフにおいて個々の残基の置換が検出さ
れた。The deduced amino acid sequence of the gene product shows four conserved regions (Pai, EF, et al., 1988), as well as sites important for GTP binding in Ras protein.
Nature, 341 , 209-214 (1989): Valencia, A., et al.,
Biochemistry, 30 , 4637-4648 (1991)), but substitution of individual residues in the two motifs was detected.
【００５３】アミノ酸配列を示す配列番号：１の１４−
２１番目の位置に示されるホスフェート結合ループを構
築するモチーフＩ（ＧxxxxＧＫＳ／Ｔ、xは如何なる残
基でもよい、以下同じ）及び１２５−１２８番目の位置
に示されるグアニン特異領域（ＮＫxＤ）と呼ばれるモ
チーフＩＩＩは、保存されていた。しかしながら、６２
−６８番目の位置に示されるモチーフＩＩにおいては、
ラットｒａｂＧＴＰタンパク（X96663）と同様に、γ−
ホスフェートと相互作用する一致領域（ＷＤＴＡＧＱ
Ｅ）内のＴｈｒがＩｌｅによって置換されていた。14- of SEQ ID NO: 1 showing the amino acid sequence
A motif I (GxxxxGKS / T, where x is any residue, the same applies hereinafter) for constructing a phosphate binding loop shown at position 21 and a motif called a guanine-specific region (NKxD) shown at positions 125-128 III was preserved. However, 62
In motif II shown at position −68,
Similar to rat rabGTP protein (X96663), γ-
Coincident regions that interact with phosphate (WDTAGQ
Thr in E) was replaced by Ile.
【００５４】また、グアニン基とその側鎖が間接的に作
用するＥxＳＡ配列（モチーフＩＶ）内の１５３−１５
６番目の位置のＡｌａがＶａｌによって置換されてい
た。この置換はマウスＲａｂ２３におけるＲxＳＶの置
換に類似している（Olkkonen, V.M., et al., Gene, 13
8, 207-211 (1994)）。Further, the 153-15 in the ExSA sequence (motif IV) in which the guanine group and its side chain act indirectly.
Ala at position 6 was replaced by Val. This substitution is similar to the substitution of RxSV in mouse Rab23 (Olkkonen, VM, et al., Gene, 13
8 , 207-211 (1994)).
【００５５】本発明遺伝子がＧＴＰ結合とＧＴＰａｓｅ
活性とを保有しているかどうかは不明ではある。ＲＡＢ
５においては、保存領域のアミノ酸置換がエンドサイト
−シス活性を下げるという報告もあることから、上記ア
ミノ酸の置換は、之等の活性になんらかの影響を及ぼす
かも知れない。The gene of the present invention has GTP binding and GTPase
It is unknown whether it has activity. RAB
In 5, it has been reported that amino acid substitutions in conserved regions decrease endocytic activity, so that substitution of the above amino acids may have some effect on their activity.
【００５６】更に本発明遺伝子の特徴は、Ｃ末端高可変
領域と２つの連続したシスティンをＣ末端に含んでいる
ことである。Further, a feature of the gene of the present invention is that it contains a C-terminal hypervariable region and two consecutive cysteines at the C-terminal.
【００５７】保存されたモチーフＩＶからの下流領域
は、Ｒａｓ関連タンパク間の配列と同様、その長さにお
いて可変的であった。この領域は特異的な標的と膜との
相互作用に係わっている（Chavrier, P., et al., Natu
re, 3 53, 769-772 (1991)）。The downstream region from the conserved motif IV was variable in length, as was the sequence between Ras-related proteins. This region is involved in specific target-membrane interactions (Chavrier, P., et al., Natu
re, 3 53, 769-772 (1991 )).
【００５８】全ての低分子量ＧＴＰ結合タンパクは、Ｃ
末端付近に少なくとも一つのシスティン残基を含んでい
て、膜相互作用に必要なＣ末端システィン・モチーフ
は、Ｃaax、ＣＣax、ＣＣ或はＣxＣ（"a"は脂肪族残
基）である。殆どのＲａｂタンパクは、Ｃ末端にＣxＣ
（例としてＲａｂ３Ａ）或はＣＣ（例としてＲａｂ１
Ａ）のどちらかを所有している。All low molecular weight GTP binding proteins are C
The C-terminal cysteine motif containing at least one cysteine residue near the end and required for membrane interaction is Caax, CCax, CC or CxC ("a" is an aliphatic residue). Most Rab proteins have CxC at the C-terminus.
(For example, Rab3A) or CC (for example, Rab1
A) You own either.
【００５９】上記結果に鑑みて、本発明遺伝子はＲａｂ
７ＧＴＰ結合類似タンパクをコードする新規なヒト遺伝
子であると結論付けられる。In view of the above results, the gene of the present invention is Rab
It is concluded that this is a novel human gene encoding a 7GTP binding analogous protein.
【００６０】（２）ノーザンブロット分析 正常ヒト組織におけるヒトｒａｂ７ＧＴＰ結合類似タン
パクｍＲＮＡの発現をランダム・オリゴヌクレオチド・
プライミング法によって、標識したヒトｃＤＮＡクロー
ンをプローブとするノーザンブロットにより評価した。(2) Northern blot analysis Expression of human rab7GTP-binding analogous mRNA in normal human tissues was determined by random oligonucleotide analysis.
The priming method was evaluated by Northern blot using a labeled human cDNA clone as a probe.
【００６１】ノーザンブロット分析は、製品使用法に従
い、ヒトＭＴＮブロット（Human Multiple Tissue Noth
ern blot; クローンテック社製、ラ・ジョラ（La Joll
a）、カリフォルニア、米国）を用いて実施した。[0061] Northern blot analysis was performed according to the product usage, using human MTN blot (Human Multiple Tissue Noth).
ern blot; Clonetech, La Joll
a), California, USA).
【００６２】即ち、上記クローンＧＥＮ−５０２Ｃ０７
のｃＤＮＡ挿入部は、３’非翻訳領域内にＡｌｕ配列を
含んでいたので、他のｍＲＮＡに対する非特異的ハイブ
リダイゼーションを予防するために、ノーザンブロット
分析用のプローブをベクター（pBluescript vector）の
ｃＤＮＡ挿入部の５’末端の上流ベクター上に存在する
ＥｃｏＲＩサイトと５８０番目（配列番号：３の配列番
号に対応）に存在するＥｃｏＲＶサイト内で割裂するこ
とによって、制限酵素断片を調製した。更に上記の特異
的な制限酵素断片をＰＣＲで増幅し、ＰＣＲ増幅産物を
［32Ｐ］−ｄＣＴＰ（ランダムプライムドＤＮＡラベリ
ングキット、ベーリンガーマンハイム社）により標識し
てプローブとした。That is, the above clone GEN-502C07
Since the cDNA insertion portion contained an Alu sequence in the 3 ′ untranslated region, a probe for Northern blot analysis was inserted into the cDNA of the vector (pBluescript vector) to prevent nonspecific hybridization to other mRNA. A restriction enzyme fragment was prepared by cleavage at the EcoRI site present on the upstream vector at the 5 'end of the insertion site and the EcoRV site present at the 580th position (corresponding to SEQ ID NO: 3). Further, the above specific restriction enzyme fragment was amplified by PCR, and the PCR amplification product was labeled with [ 32 P] -dCTP (random primed DNA labeling kit, Boehringer Mannheim) to obtain a probe.
【００６３】ブロットを４時間プレハイブリ後、４２℃
で一晩、５０％ホルムアミド／５×ＳＳＣ／１０×デン
ハルツ溶液／２％ＳＤＳ溶液（１００μｇ／ｍｌ変性サ
ケ***ＤＮＡ含有）の溶液中でハイブリした。２×ＳＳ
Ｃ／０．０５％ＳＤＳにて室温下にて６０分、２回洗浄
後、次いで０．１×ＳＳＣ／０．０１％ＳＤＳにて６５
℃下に６０分間で３回洗浄した。フィルターを−８０℃
下に３日間、Ｘ線フィルム（コダック社製）に対して露
光した。After prehybridizing the blot for 4 hours,
Overnight in a solution of 50% formamide / 5 × SSC / 10 × Denhartz solution / 2% SDS solution (containing 100 μg / ml denatured salmon sperm DNA). 2 x SS
After washing twice with C / 0.05% SDS at room temperature for 60 minutes, then 65% with 0.1 × SSC / 0.01% SDS.
The plate was washed three times at 60 ° C for 60 minutes. Filter at -80 ° C
Exposure to X-ray film (Kodak) for 3 days below.
【００６４】３日間の露光の結果、試験した全てのヒト
組織（心臓、脳、胎盤、肺、肝臓、骨格筋、腎臓、膵
臓、脾臓、甲状腺、膀胱、コウ丸、卵巣、大腸、小腸、
末梢血リンパ球）内に、３．６ｋｂのｍＲＮＡが発現し
ていることが明らかとなった。しかしながら、脳、胎
盤、骨格筋においては、わずかに検出された。As a result of the three-day exposure, all human tissues tested (heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thyroid, bladder, ko gan, ovary, large intestine, small intestine,
It was revealed that 3.6 kb of mRNA was expressed in peripheral blood lymphocytes). However, it was slightly detected in brain, placenta and skeletal muscle.
【００６５】（３）ダイレクト・Ｒ−バンディングＦＩ
ＳＨ（Fluoresence in situ hybridization）によるコ
スミド・クローンと染色体の局在 ＦＩＳＨ分析用のプローブを調整するために、ＧＥＮ−
５０２Ｃ０７遺伝子に相当する配列を含むコスミド・ク
ローンを単離した。即ち、下記表１に示す塩基配列のプ
ライマーＰ１とＰ２とを合成し、之等のプライマーを用
いてＰＣＲを行ない、コスミド・クローンのスクリーニ
ングを行なった。反応条件としては、９４℃３０秒、５
５℃４５秒及び７２℃４５秒のサイクルを３５サイクル
行なった。(3) Direct R-Banding FI
Localization of cosmid clone and chromosome by SH (Fluoresence in situ hybridization) In order to prepare a probe for FISH analysis, GEN-
A cosmid clone containing the sequence corresponding to the 502C07 gene was isolated. That is, primers P1 and P2 having the nucleotide sequences shown in Table 1 below were synthesized, PCR was performed using these primers, and cosmid clones were screened. The reaction conditions were 94 ° C. for 30 seconds, 5
35 cycles of 5 ° C. for 45 seconds and 72 ° C. for 45 seconds were performed.
【００６６】[0066]
【表１】 [Table 1]
【００６７】かくして単離されたひとつのコスミド・ク
ローンを複製プロメタフェーズＲ−バンドと組み合わせ
たＦＩＳＨに基づく技術であるダイレクト・Ｒ−バンデ
ィング・フルオレッセン・インサイチュー・ハイブリダ
イゼーション（ＦＩＳＨ）によるマッピングのためのプ
ローブとして使用し、該ＦＩＳＨ法によって、ＧＥＮ−
５０２Ｃ０７の染色体マッピングを行なった〔Takahash
i, E., et al., Hum.Genet., 86, 14-16 (1990)〕。One cosmid clone thus isolated was combined with a replication prometaphase R-band for mapping by FISH-based technology, direct R-banding fluorescein in situ hybridization (FISH). Used as a probe for GEN- by the FISH method.
Chromosome mapping of 502C07 was performed [Takahash
i, E., et al., Hum. Genet., 86 , 14-16 (1990)].
【００６８】また、該クローンに存在する反復配列の抑
制のために、リクター〔Lichter P.et al., Proc. Nat
l. Sci. U.S.A., 87, 6634-6638 (1990)〕の記載に従っ
て、２０倍過度のヒトＣｏｔ−Ｉ ＤＮＡ（ＢＲＬ社
製）を用いた。In order to suppress repetitive sequences present in the clone, Lecter [Lichter P. et al., Proc. Nat.
l. Sci. USA, 87 , 6634-6638 (1990)], a 20-fold excess of human Cot-I DNA (BRL) was used.
【００６９】標識、ハイブリダイゼーション、洗浄、検
出は、通常の方法に従い実施した。プロビア１００フィ
ルム（フジＩＳＯ１００；ブシ・フィルム社製）を顕微
鏡写真撮影のために用いた（フィルター・コンビネーシ
ョン、ニコンＢ−２Ａ）。Labeling, hybridization, washing and detection were carried out according to the usual methods. Provia 100 film (Fuji ISO 100; manufactured by Bushi Film Co., Ltd.) was used for microphotographing (filter combination, Nikon B-2A).
【００７０】試験した１００のＲ−バンド***前中期プ
レートの４７％が、第１染色体のバンドｑ３２．１の位
置で相同染色体上に完全な１対のスポットを示した。ま
た、プレートの４１％がどちらか或は相同染色体上に不
完全な単一又は一対のスポットを明らかにした。残りの
１２％は、検出可能なスポットを示さなかった。上記の
結果から、ＧＥＮ−５０２Ｃ０７は、染色体バンド１ｑ
３２上にマップされた。47% of the 100 R-band premetaphase plates tested showed a complete pair of spots on homologous chromosomes at band q32.1 on chromosome 1. Also, 41% of the plates revealed incomplete single or paired spots on either or homologous chromosomes. The remaining 12% showed no detectable spots. From the above results, GEN-502C07 shows that chromosome band 1q
32.
【００７１】本実施例によれば、新規なヒトｒａｂ７Ｇ
ＴＰ結合類似タンパク遺伝子が提供され、該遺伝子を用
いれば、該遺伝子の各種組織での発現の検出や、ヒトｒ
ａｂ７ＧＴＰ結合類似タンパクの遺伝子工学的製造が可
能となり、これらにより、発現タンパクとｒａｂによる
細胞内小胞輸送の制御機構の解明の研究や之等の関与す
る疾患、例えば癌、神経性疾患、等の病態解明や診断、
治療等が可能となると考えられる。According to this example, a novel human rab7G
The present invention provides a TP-binding similar protein gene, which can be used to detect the expression of the gene in various tissues,
Genetically engineered production of ab7GTP-binding analogous proteins has become possible, which enables studies on the elucidation of the regulation mechanism of intracellular vesicle transport by expressed proteins and rab, and diseases involving them, such as cancer and neurological diseases. Elucidation of pathological condition and diagnosis,
It is considered that treatment or the like is possible.
【００７２】[0072]
【実施例２】ミエロイド抗原ＣＤ３３関連蛋白遺伝子
（ＧＥＮ−５６０Ｄ０６ｌ及びＧＥＮ−５６０Ｄ０６
ｓ） （１）ミエロイド抗原ＣＤ３３関連蛋白遺伝子のクロー
ニング及びＤＮＡシークエンシング イムノグロブリン（Ｉｇ）・スーパーファミリーに属す
るメンバーは、細胞−細胞間相互作用を介在している分
子として働く〔Williams, A.F., Annu. Rev. Immunol.,
6, 381 (1988)〕。Example 2 Myeloid antigen CD33-related protein genes (GEN-560D061 and GEN-560D06)
s) (1) Cloning and DNA Sequencing of the Myeloid Antigen CD33-Related Protein Gene Members belonging to the immunoglobulin (Ig) superfamily act as molecules that mediate cell-cell interactions [Williams, AF, Annu Rev. Immunol.,
6 , 381 (1988)].
【００７３】近年、シアル酸結合蛋白として特徴付けら
れているシアロアドヘシンファミリーが、Ｉｇスーパー
ファミリーのサブ・グループのメンバーとして、Ｂ細胞
特異的マーカー〔Wilson, G.L., et al., J. Exp. Me
d., 173, 137 (1991): Stamenkovic, I., and Seed,
B., Nature, 345, 74 (1990)〕、オリゴデンドロサイト
とシュワン細胞上に発現されているミエリン関連糖蛋白
（ＭＡＧ）〔Fujita, N.,et al., B.B.R.C., 1 65, 116
2 (1989)〕、ミエロイド分化抗原ＣＤ３３〔Peiper, S.
C., et al., Blood, 72, 314 (1988): Simmons, D.L.,
and Seed, B., J.Immunol., 141, 2797 (1988)：Tchili
an, E.Z., et al., Blood, 83, 3188 (1994)）及び組織
マクロファージの個体群中に発現されているシアロアド
ヘシン〔Crocker, P.R., et al., Embo., 13, 4490 (19
94)〕等が報告されている。In recent years, the sialoadhesin family, which has been characterized as a sialic acid binding protein, has been identified as a member of the Ig superfamily subgroup by a B cell specific marker [Wilson, GL, et al., J. Exp. Me
d., 173 , 137 (1991): Stamenkovic, I., and Seed,
B., Nature, 345, 74 ( 1990) ], myelin-associated glycoprotein which is expressed in oligodendrocytes and on Schwann cells (MAG) [Fujita, N., et al., BBRC, 1 65, 116
2 (1989)], myeloid differentiation antigen CD33 (Peiper, S.
C., et al., Blood, 72 , 314 (1988): Simmons, DL,
and Seed, B., J. Immunol., 141 , 2797 (1988): Tchili
an, EZ, et al., Blood, 83 , 3188 (1994)) and sialoadhesin expressed in a population of tissue macrophages [Crocker, PR, et al., Embo., 13 , 4490 (19).
94)] has been reported.
【００７４】これまでは、このファミリーがＣＤ２２に
属していると考えられており、上記４つのメンバーがＩ
ｇスーパーファミリーのサブ・グループ制定された〔Cr
ocker, P.R., et al., Embo., 13, 4490 (1994): Muckl
ow, S., et al., Genomics,28, 344 (1995): Kelm, S.,
et al., Curr. Biol., 4, 965 (1994): Freeman, S.
D., et al., Blood, 85, 2005 (1995)〕。Previously, this family was thought to belong to CD22, and the four members
Established a sub-group of the super family [Cr
ocker, PR, et al., Embo., 13 , 4490 (1994): Muckl
ow, S., et al., Genomics, 28 , 344 (1995): Kelm, S.,
et al., Curr.Biol., 4 , 965 (1994): Freeman, S.
D., et al., Blood, 85 , 2005 (1995)].
【００７５】之等の分子は、細胞表面上の特異的シアル
化したグリカンの認知を通して、シアル酸を含む〔Kel
m, S., et al., Curr. Biol., 4, 965 (1994)〕細胞表
面グリカンに結合することによって細胞接着を媒介する
ことができる。上記特異的認知によって好中球に対する
シアロアドヘシン、ニューロンに対するミエリン関連糖
蛋白、リンパ球に対するＣＤ２２及び赤血球に対するＣ
Ｄ３３の選択的結合に導くとされている〔Kelm, S., et
al., Curr. Biol., 4, 965 (1994): Freeman, S.D., e
t al., Blood, 85, 2005 (1995)〕。These molecules contain sialic acid through the recognition of specific sialylated glycans on the cell surface [Kel
m, S., et al., Curr. Biol., 4 , 965 (1994)] can mediate cell adhesion by binding to cell surface glycans. Due to the specific cognition, sialoadhesin for neutrophils, myelin-related glycoprotein for neurons, CD22 for lymphocytes and C for erythrocytes
It has been shown to lead to selective binding of D33 [Kelm, S., et al.
al., Curr. Biol., 4 , 965 (1994): Freeman, SD, e.
t al., Blood, 85 , 2005 (1995)].
【００７６】上記の蛋白は、この区別可能なサブ・グル
ープ間の配列類似性を共有するが、Ｉｇ様領域の隣接し
たＣ２−セットと同様にＮ末端Ｖ−セットＩｇ様領域ド
メインのＩｇスーパーファミリーの他のメンバーとシア
ロアドヘシンのメンバーのある程度の相同性が維持され
ていた〔Freeman, S.D., et al., Blood, 85, 2005 (19
95)〕。The above proteins share sequence similarity between these distinct subgroups, but share the Ig superfamily of N-terminal V-set Ig-like region domains as well as adjacent C2-sets of Ig-like regions. Some homology of sialoadhesin members to other members of the family was maintained [Freeman, SD, et al., Blood, 85 , 2005 (19
95)].
【００７７】本例では、実施例１−（１）に準じて、ヒ
ト胎盤ｃＤＮＡライブラリーから無作為に選択したｃＤ
ＮＡクローンのＤＮＡ配列を決定し、公知の遺伝子とＤ
ＮＡ配列を比較することによって、ＧＥＮ−５６０Ｄ０
６と名付けられた１．９ｋｂのｃＤＮＡクローンがミエ
ロイド抗原ＣＤ３３に対して高い相同性を有することを
明らかにする。In this example, according to Example 1- (1), a cD randomly selected from a human placenta cDNA library was used.
The DNA sequence of the NA clone was determined and the known gene and D
By comparing NA sequences, GEN-560D0
The 1.9 kb cDNA clone, designated No. 6, reveals high homology to the myeloid antigen CD33.
【００７８】尚、このクローンは遺伝子の５’末端部分
が欠失していたので、欠けているセグメントを単離する
ために、新たにヒト胎盤ｃＤＮＡライブラリーのスクリ
ーニングを行なった。Since this clone lacked the 5 'end of the gene, a new human placenta cDNA library was screened in order to isolate the missing segment.
【００７９】即ち、プローブとして［32Ｐ］ランダム−
標識ｃＤＮＡを持つラムダ・ｔｒｐｌＥＸベクターを用
いて胎盤のｍＲＮＡ（ストラトジーン社製）から構築さ
れたｃＤＮＡライブラリー（約１００万のプラーク）を
スクリーニングし、１２の付加的なｃＤＮＡクローンを
得た。それらの中から、３つのクローンが全体のオープ
ン・リーディング・フレームをカバーしていることが後
に判明した。That is, [ 32 P] random-
Using a lambda trplEX vector having a labeled cDNA, a cDNA library (about 1 million plaques) constructed from placental mRNA (manufactured by Stratogene) was screened to obtain 12 additional cDNA clones. Among them, it was later found that three clones covered the entire open reading frame.
【００８０】それらのＤＮＡ配列を［35Ｓ］ｄＡＴＰを
用いるジデオキシ・ターミネーション法によって決定し
た〔Sanger, F., et al., Proc. Natl. Acad. Sci. U.
S.A., 74, 560 (1977)〕。The DNA sequences were determined by the dideoxy termination method using [ 35 S] dATP [Sanger, F., et al., Proc. Natl. Acad. Sci.
SA, 74 , 560 (1977)].
【００８１】その結果、ＧＥＮ−５６０Ｄ０６遺伝子に
ついて、配列番号：６に２８０９塩基の核酸配列からな
る全長配列、配列番号：５に１３２６塩基のオープン・
リーディング・フレームを含む核酸配列並びに配列番
号：４に核酸配列によってコードされる４４２アミノ酸
残基からなる推定アミノ酸配列を示す。As a result, regarding the GEN-560D06 gene, SEQ ID NO: 6 shows a full-length sequence consisting of a 2809 nucleotides nucleic acid sequence, and SEQ ID NO: 5 has an open nucleotide sequence of 1326 nucleotides.
The nucleic acid sequence containing the reading frame and SEQ ID NO: 4 show the deduced amino acid sequence consisting of 442 amino acid residues encoded by the nucleic acid sequence.
【００８２】ＧＥＮ−５６０Ｄ０６遺伝子の５’非コー
ド配列は、２３６のＧＣリッチ配列から成っていて、ポ
リＡティルによって続く４つの可能性あるポリアデニレ
ーション・シグナル（ＡＡＴＡＡＡ）が３’非コード領
域上に見られた。The 5 'non-coding sequence of the GEN-560D06 gene consists of 236 GC-rich sequences, with four possible polyadenylation signals (AATAAA) followed by a poly-A tail on the 3' non-coding region. Was seen in
【００８３】上記完全なフォームに加えて、このｃＤＮ
Ａクローンがおそらくオールターナティブ・（二者択一
的な）スプライシングによってオリジナルなクローンの
ヌクレオチド配列の１２１６−１３９１塩基目の間の１
７６塩基対が欠けていることが分かった。該１７６塩基
対欠失は、リーディング・フレームのシフトの結果とし
てであって、この転写体から推定タンパクの計算された
サイズは、３４２アミノ酸であった。In addition to the complete form described above, this cDN
The A clone is supposed to be the one between bases 1216-1391 of the nucleotide sequence of the original clone, possibly due to alternative (alternative) splicing.
It was found that 76 base pairs were missing. The 176 base pair deletion was the result of a reading frame shift, and the calculated size of the putative protein from this transcript was 342 amino acids.
【００８４】従って、前記長い方のｃＤＮＡクローンで
あるＧＥＮ−５６０Ｄ０６遺伝子をＧＥＮ−５６０Ｄ０
６ｌ遺伝子とし、該クローンより１７６塩基対が欠失し
た遺伝子をＧＥＮ−５６０Ｄ０６ｓ遺伝子とした。Therefore, the longer cDNA clone, GEN-560D06 gene, was replaced with GEN-560D0 gene.
This gene was designated as a 6l gene, and the gene having 176 base pairs deleted from the clone was designated as a GEN-560D06s gene.
【００８５】上記ＧＥＮ−５６０Ｄ０６ｓ遺伝子につい
て、配列番号：９に１７４１塩基からなる全配列を、配
列番号：８に１０２６塩基のオープン・リーディング・
フレームを含む核酸配列を、また配列番号：７に上記核
酸配列によってコードされる３４２アミノ酸残基からな
るアミノ酸配列を、それぞれ示す。Regarding the above-mentioned GEN-560D06s gene, the entire sequence consisting of 1741 nucleotides is shown in SEQ ID NO: 9 and the open reading sequence of 1026 nucleotides is shown in SEQ ID NO: 8.
The nucleic acid sequence containing the frame is shown, and SEQ ID NO: 7 shows the amino acid sequence consisting of 342 amino acid residues encoded by the nucleic acid sequence.
【００８６】データ・ベースの公知のタンパクと推定蛋
白のコンピュータ分析により、本発明遺伝子によってコ
ードされる推定タンパク配列は、ミエロイド抗原ＣＤ３
３の膜貫通に対して高い相同性を示していて（５６
％）、配列的に２５の疎水性残基（３３３−３５７塩
基）を含んでいた。該領域は膜貫通領域をもコードして
いるようであった。By computer analysis of known proteins and putative proteins in the database, the putative protein sequence encoded by the gene of the present invention was identified as a myeloid antigen CD3.
3 show high homology to the transmembrane (56
%), Which sequenced to contain 25 hydrophobic residues (333-357 bases). The region also appeared to encode a transmembrane region.
【００８７】加えてタンパクの推定された成熟体は、細
胞外領域（配列番号：４に示す２０−３３３の３１４ア
ミノ酸残基）と８５アミノ酸残基の細胞質領域からなっ
ている。In addition, the predicted mature form of the protein consists of an extracellular region (314 amino acid residues of 20-333 shown in SEQ ID NO: 4) and a cytoplasmic region of 85 amino acid residues.
【００８８】本発明遺伝子の細胞外領域において、配列
番号：４の２０−１３１アミノ酸残基、１３２−２２４
アミノ酸残基及び２２５−３２６アミノ酸残基の３つの
Ｉｇに関連したセグメントと、Ｉｇスーパーファミリー
に属しているメンバーにおいて観察されたＩｇ様ドメイ
ンのＶ−セットとの２つのＣ２−セットに対する類似性
が明らかになった〔Williams, A.F., Annu. Rev. Immun
ol., 6, 381 (1988):Williams, A.F., Immunol. Today,
8, 298 (1987): Williams, A. F., et al.,Cold Sprin
g Harbor Symp. Quant. Biol., 54, 637 (1989)〕。In the extracellular region of the gene of the present invention, amino acid residues 20-131 of SEQ ID NO: 4, 132-224
The similarity to two C2-sets of amino acid residues and three Ig-related segments of 225-326 amino acid residues and the V-set of Ig-like domains observed in members belonging to the Ig superfamily. Revealed [Williams, AF, Annu. Rev. Immun
ol., 6 , 381 (1988): Williams, AF, Immunol. Today,
8 , 298 (1987): Williams, AF, et al., Cold Sprin
g Harbor Symp. Quant. Biol., 54 , 637 (1989)].
【００８９】シアロアドヘシンファミリーの他のメンバ
ーと同様に、ＣＤ３３の所望の構造と、この新規な遺伝
子のアミノ酸配列の比較に基づき、推定されたタンパク
はＮ末端Ｖドメインと膜貫通領域と細胞質の尾部に続く
２つの隣接Ｃ２様ドメインの構造を有すると考えられ、
特に、このタンパクの第１と第２のＩｇ様のドメイン
は、ＣＤ３３のそれと高い相同性（７２％アミノ酸同
一）を示した。As with the other members of the sialoadhesin family, based on a comparison of the desired structure of CD33 and the amino acid sequence of this novel gene, the deduced protein has an N-terminal V domain, a transmembrane region and cytoplasmic Thought to have the structure of two adjacent C2-like domains following the tail,
In particular, the first and second Ig-like domains of this protein showed high homology (72% amino acid identity) to that of CD33.
【００９０】Ｉｇスーパーファミリーを定義するペプチ
ドの特異的なモチーフの保存より、この新規な分子がＣ
Ｄ３３と同様にＩｇ遺伝子スーパーファミリーのメンバ
ーとして分類することができると提言された〔William
s, A.F., Annu. Rev. Immunol., 6, 381 (1988)〕。Due to the conservation of specific motifs of the peptides defining the Ig superfamily, this novel molecule
It has been proposed that it can be classified as a member of the Ig gene superfamily in the same way as D33 [William
s, AF, Annu. Rev. Immunol., 6 , 381 (1988)].
【００９１】（３）ノーザンブロット分析 種々の組織においてこの遺伝子の発現を試験するため
に、ヒトＭＴＮブロット・システム（クローンテック社
製）を用い、実施例１−（２）と同様にしてＧＥＮ−５
６０Ｄ０６ｃＤＮＡクローン全領域をプローブとするノ
ーザンブロット分析を行なった。(3) Northern blot analysis In order to test the expression of this gene in various tissues, the GEN-blot was performed in the same manner as in Example 1- (2) using a human MTN blot system (Clontech). 5
Northern blot analysis was performed using the entire region of the 60D06 cDNA clone as a probe.
【００９２】ブロットを６時間プレハイブリダイズさせ
た後、４２℃で１８時間、５０％ホルムアミド／５×Ｓ
ＳＰＥ／１０×デンハルツ溶液／２％ＳＤＳ溶液（１０
０μｇ／ｍｌ変性サケ***ＤＮＡ含有）の溶液中でハイ
ブリダイズした。ブロットは２×ＳＳＣ／０．０５％Ｓ
ＤＳにて室温下に２回溶液を交換し、４０分間洗浄した
後、０．１×ＳＳＣ／０．１％ＳＤＳにて５０℃下に４
０分間で２回洗浄した。フィルターは−８０℃下、１８
時間、Ｘ線フィルム（コダック社製）に対して露光し
た。The blots were prehybridized for 6 hours and then incubated at 42 ° C. for 18 hours in 50% formamide / 5 × S
SPE / 10 × Denhartz solution / 2% SDS solution (10
(Containing 0 μg / ml denatured salmon sperm DNA). Blot is 2 × SSC / 0.05% S
The solution was exchanged twice at room temperature with DS, washed for 40 minutes, and then washed with 0.1 × SSC / 0.1% SDS at 50 ° C. for 4 minutes.
Washed twice for 0 minutes. Filter at -80 ° C, 18
Exposure was performed for an X-ray film (manufactured by Kodak Company) for a time.
【００９３】心臓、脳、胎盤、肺、肝臓、骨格筋、腎
臓、膵臓、脾臓、甲状腺、卵巣、前立腺、コウ丸、小
腸、大腸及び末梢血リンパ球の１６の成人組織と、胎児
心臓、胎児脳、胎児肺、胎児肝臓及び胎児腎臓の５つの
胎児組織とから、ｍＲＮＡを使用するノーザン・ブロッ
ト分析の結果、この遺伝子は胎盤に特異的に発現するこ
とが明らかになった。Sixteen adult tissues of heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thyroid, ovary, prostate, komaru, small intestine, large intestine and peripheral blood lymphocytes, fetal heart, fetus Northern blot analysis using mRNA from five fetal tissues, brain, fetal lung, fetal liver and fetal kidney, revealed that this gene was specifically expressed in the placenta.
【００９４】４つの異なるサイズからなる７．５ｋｂ、
５．０ｋｂ、４．１ｋｂ及び１．９ｋｂの転写体が観察
されたので、プローブとしてｃＤＮＡ配列の一部を使用
してそれらの更なる特徴付けを行なった。7.5 kb of four different sizes,
Since 5.0 kb, 4.1 kb and 1.9 kb transcripts were observed, their further characterization was performed using a portion of the cDNA sequence as a probe.
【００９５】その結果、配列番号：６の１２１６−１３
９１番目のヌクレオチドで推定膜貫通領域に相同するＰ
ＣＲ産物の１７６塩基対が、プローブとして使用された
全体のｃＤＮＡと同様に、同じバンドで検出された。最
も短い転写体は、１８９１−１８９６番目の位置でポリ
アデニレーション・シグナルに使用されているようであ
る。なぜなら、オリジナルなｃＤＮＡ（配列番号：６の
２４９１−２８０５番目に相当）の３’末端側の３１５
塩基対のＰＣＲ産物をプローブとして使用した時、１．
９ｋｂの最も小さい転写体は検出されず、従って、この
１．９ｋｂの産物は１つの異なるポリＡサイトの使用の
ように見えることを示しているからである。事実、本発
明者らは、オリジナル・クローンの１９１８番目（配列
番号：６）でポリＡを含んでいるｃＤＮＡクローンを得
ている。As a result, 1216-13 of SEQ ID NO: 6
A P homologous to the putative transmembrane region at nucleotide 91
176 base pairs of the CR product were detected in the same band, as was the entire cDNA used as a probe. The shortest transcript appears to be used for the polyadenylation signal at positions 1891-1896. This is because 315 at the 3 'end of the original cDNA (corresponding to positions 2491-2805 of SEQ ID NO: 6).
When a base pair PCR product was used as a probe:
The 9 kb smallest transcript was not detected, thus indicating that the 1.9 kb product appeared to use one different polyA site. In fact, we have obtained a cDNA clone containing polyA at position 1918 (SEQ ID NO: 6) of the original clone.
【００９６】更に、おそらくオールターナティブ（二者
択一的）・スプライシングによる膜貫通領域と細胞質尾
部を欠く３４２のアミノ酸をコードするスプライスした
転写体を、２つのクローンのうちの１つから単離した。In addition, a spliced transcript encoding 342 amino acids lacking a transmembrane region and a cytoplasmic tail, presumably due to alternative splicing, was isolated from one of the two clones.
【００９７】このクローンは３番目のＩｇ様ドメインの
末端に相同する１２１５番目（配列番号：６）のヌクレ
オチドまで膜貫通型と同一であるオープン・リーディン
グ・フレームを持っていた。その後、１７６塩基対の欠
失は、リーディング・フレームのシフトを生じている。This clone had an open reading frame identical to the transmembrane type up to nucleotide 1215 (SEQ ID NO: 6) homologous to the end of the third Ig-like domain. Subsequently, the 176 base pair deletion has resulted in a reading frame shift.
【００９８】更なる１６アミノ酸をコードする別のフレ
ームと１４３９番目（配列番号：６）のヌクレオチドの
ＴＧＡターミネーション・コドンは、膜貫通フォームを
提供していない。膜貫通型の所望の構造との比較に基づ
いて、オールターナティブ（二者択一的）にスプライス
したフォームの産物は、膜貫通領域と細胞質尾部を欠い
ている。Another frame encoding an additional 16 amino acids and the TGA termination codon at nucleotide 1439 (SEQ ID NO: 6) do not provide a transmembrane form. Based on a comparison to the desired transmembrane structure, the product of the alternatively spliced foam lacks the transmembrane region and the cytoplasmic tail.
【００９９】３つの大きな転写体は、更に下流にオール
ターナティブ（二者択一的）なポリＡシグナルによって
もたらされているかも知れない。かわりとして、２つ又
はそれ以上の細胞質変異体を産生するＩｇ−遺伝子スー
パーファミリーに属するＭＡＧ、ＣＥＡ或はマウスＣＤ
３３のような他の接着分子〔Tchilian, E.Z., et al.,
Blood, 83, 3188 (1994): Williams, A.F., Immunol. T
oday, 8, 298 (1987):Williams, A. F., et al., Cold
Spring Harbor Symp. Quant. Biol., 54, 637(1989)〕
のように、この新規な遺伝子は、オールターナティブ・
（二者択一的な）スプライシングによって細胞質領域に
おいて異なった同位体を産生するかもしれない。The three large transcripts may be driven further downstream by an alternative poly-A signal. Alternatively, a MAG, CEA or mouse CD belonging to the Ig-gene superfamily that produces two or more cytoplasmic variants
33 (Tchilian, EZ, et al.,
Blood, 83 , 3188 (1994): Williams, AF, Immunol. T
oday, 8 , 298 (1987): Williams, AF, et al., Cold.
Spring Harbor Symp.Quant.Biol., 54 , 637 (1989)]
This novel gene is an alternative
(Alternative) splicing may produce different isotopes in the cytoplasmic region.
【０１００】ＭＡＧは、シアロアドヘシンのメンバーで
あると報告されている。これは細胞質領域において区別
される２つの型の同位体を産生するミエリン形成におい
て重要な役割を持っており、それらの発現は進化の段階
の特別な方法において調節されることが提言される〔La
i, C., et al., Proc. Natl. Acad. Sci. U.S.A., 84,
4337 (1987)〕。ＭＡＧに対するこの証拠から、本発明
者らは胎盤の進化の段階はおそらく本発明遺伝子の発現
を調節する一つの重要な因子であって、それが胎盤の成
長において重要な役割を演ずると考える。MAG has been reported to be a member of sialoadhesin. It has an important role in myelination that produces two types of isotopes that are distinct in the cytoplasmic region, and it is suggested that their expression is regulated in a special way at the stage of evolution [La
i, C., et al., Proc. Natl. Acad. Sci. USA, 84 ,
4337 (1987)]. From this evidence for MAG, we believe that the stage of placental evolution is probably one important factor that regulates the expression of the genes of the present invention, and that it plays an important role in placental growth.
【０１０１】また、得られた配列がキメラでないことの
確認及びスプライシング産物を確認する目的で、以下に
示す逆転写−ＰＣＲ（ＲＴ−ＰＣＲ）法を実施した。In order to confirm that the obtained sequence was not a chimera and to confirm a spliced product, the following reverse transcription-PCR (RT-PCR) method was carried out.
【０１０２】（４）ＲＴ−ＰＣＲ 正常に分娩された胎盤から抽出されたＰoly（Ａ）＋Ｒ
ＮＡの１μｇをランダム・プライマーｐ（ｄＮ）６（ベ
ーリンガー・マインハイムＧｍｂＨ社製）で逆転写して
ｃＤＮＡを得、これを下記表２に示す塩基配列の遺伝子
特異的プライマーＦ７及びＲを用いたＰＣＲにより増幅
させた。(4) RT-PCR Poly (A) + R extracted from a placenta normally delivered
1 μg of NA was reverse-transcribed with random primer p (dN) 6 (Boehringer-Mainheim GmbH) to obtain cDNA, which was subjected to PCR using gene-specific primers F7 and R having the nucleotide sequences shown in Table 2 below. Amplified.
【０１０３】[0103]
【表２】 [Table 2]
【０１０４】尚、 ここで用いたＦ７及びＲ６プライマ
ーは常法に従い合成されたものであり、上記ＰＣＲの反
応条件は、９４℃３０秒、５５℃３０秒、７２℃３０秒
のサイクルを２５サイクル行なった。ＲＴ−ＰＣＲ産物
は２％アガロース・ゲル電気泳動により分析した。その
結果、両転写体が胎盤内に発現したが、オールターナテ
ィブ（二者択一的）にスプライシングしたフォームに相
同する転写体が膜貫通型のそれより、発現量が少ないと
考えられた。The F7 and R6 primers used herein were synthesized according to a conventional method, and the reaction conditions of the PCR were 25 cycles of 94 ° C. for 30 seconds, 55 ° C. for 30 seconds, and 72 ° C. for 30 seconds. Done. RT-PCR products were analyzed by 2% agarose gel electrophoresis. As a result, although both transcripts were expressed in the placenta, it was considered that the transcripts homologous to the alternatively (alternatively) spliced form had a lower expression level than the transmembrane type.
【０１０５】上記のことから、本発明者らの示すデータ
はＣＤ３３のような細胞−細胞間相互作用と関連してい
るらしい胎盤特異的遺伝子産物の存在を示唆している。From the above, the data presented by the present inventors suggest the presence of a placenta-specific gene product, such as CD33, which may be associated with cell-cell interactions.
【０１０６】本例によれば、新規なヒトＧＥＮ−５６０
Ｄ０６遺伝子が提供され、該遺伝子を用いれば、該遺伝
子の胎盤組織での発現の検出や、ヒトＧＥＮ−５６０Ｄ
０６遺伝子の遺伝子工学的製造が可能となり、これらに
より、前述したようにＣＤ３３のような細胞−細胞間相
互作用と関連の研究や胎盤の進化及び機能の解析や、こ
れが関与する各種疾患、例えば、欠損により不妊症等の
診断等を行なうことができ、またこれらの治療及び予防
薬のスクリーニングや評価等をも行なうことができる。According to this example, the novel human GEN-560
The D06 gene is provided, and if the gene is used, the expression of the gene in placental tissue can be detected or the human GEN-560D
Genetic engineering production of the 06 gene is enabled, and as described above, cell-cell interactions such as CD33 and related studies, analysis of placental evolution and function, and various diseases involving this, for example, The deficiency enables diagnosis of infertility and the like, and screening and evaluation of these therapeutic and preventive drugs.
【０１０７】[0107]
【実施例３】脳脂肪酸結合蛋白遺伝子 （１）脳脂肪酸結合蛋白遺伝子のクローニング及びＤＮ
Ａシークエンシング 長鎖脂肪酸やそのＣｏＡ誘導体又は小分子の疎水性のリ
ガンドに対して高い親和性で結合する脂肪酸結合蛋白
(ＦＡＢＰ)は、いくつかの組織の細胞質において豊富に
発現されている。Example 3 Brain Fatty Acid Binding Protein Gene (1) Cloning of Brain Fatty Acid Binding Protein Gene and DN
A-sequencing Fatty acid binding proteins that bind with high affinity to long chain fatty acids, their CoA derivatives or small molecule hydrophobic ligands
(FABP) is abundantly expressed in the cytoplasm of some tissues.
【０１０８】該ＦＡＢＰは脂肪酸の細胞内への取り込み
を高めて、β−酸化、リン脂質のような脂肪酸代謝の過
程に関連する酵素に関して刺激的な効果を持っている(V
eerkamp, J. H., and Matman, R. G., Prog. Lipid Re
s., 34, 17-52(1995))。The FABP enhances the uptake of fatty acids into cells and has a stimulating effect on enzymes involved in the process of fatty acid metabolism, such as β-oxidation and phospholipids (V
eerkamp, JH, and Matman, RG, Prog. Lipid Re
s., 34 , 17-52 (1995)).
【０１０９】小分子１４−１６ｋＤａ蛋白であるＦＡＢ
Ｐは、単離された臓器の由来から命名されている。ＦＡ
ＢＰの少なくとも８つの構造的に異なったタイプが存在
し、脳、肝臓、心臓又は筋肉、そして腸の、表皮の、回
腸の肥満細胞とミエリンから単離されている。細胞質性
のレチノ−ル酸結合蛋白ＩとＩＩもＦＡＢＰファミリー
のメンバーである。ヒトＦＡＢＰｓは腸、心臓、骨格
筋、肝臓、及び脂肪から単離されているが、未だ脳から
は単離されていない。FAB, a Small Molecule 14-16 kDa Protein
P is named from the origin of the isolated organ. FA
There are at least eight structurally different types of BP that have been isolated from brain, liver, heart or muscle, and intestinal, epidermal, ileal mast cells and myelin. Cytoplasmic retinoic acid binding proteins I and II are also members of the FABP family. Human FABPs have been isolated from intestine, heart, skeletal muscle, liver, and fat, but not yet from the brain.
【０１１０】実施例１−（１）と同様の方法でヒト胎児
脳ｃＤＮＡライブラリーから任意に選択したｃＤＮＡク
ローンの配列解析とデータ・ベースの検索の結果、脂肪
酸結合蛋白のメンバーに対してその最も強い相同性を示
した一つのクローンを見つけ出し、該クローンをＧＥＮ
−１２８Ｂ１０と命名した。As a result of sequence analysis and database search of a cDNA clone arbitrarily selected from the human fetal brain cDNA library in the same manner as in Example 1- (1), One clone showing strong homology was found and the clone was identified as GEN.
It was named -128B10.
【０１１１】上記該ＧＥＮ−１２８Ｂ１０クローンの塩
基配列は、配列番号：１２で示されるように７５４塩基
からなり、配列番号：１１で示される３９６塩基のオー
プン・リーディング・フレームを含んでいた。また、配
列番号：１０に前記核酸配列でコードされる１３２のア
ミノ酸残基からなる推定アミノ酸配列を示す。開始コド
ンは、配列番号：１２の塩基配列番号の５２番目から始
まり、４４８番目が終始コドンを示していた。The nucleotide sequence of the above-mentioned GEN-128B10 clone consisted of 754 nucleotides as shown in SEQ ID NO: 12 and contained an open reading frame of 396 nucleotides shown in SEQ ID NO: 11. In addition, SEQ ID NO: 10 shows a deduced amino acid sequence consisting of 132 amino acid residues encoded by the nucleic acid sequence. The start codon started from the 52nd position of the base sequence number of SEQ ID NO: 12, and the 448th position showed a termination codon.
【０１１２】ＦＡＳＴＡプログラムの相同性検索によっ
て、単離された遺伝子がラット脳(Bennett, E., et a
l., J. Neurochem., 63, 1616-1624(1994))、マウス脳
(Feng,L., et al., Neuron, 12(4) 895-908 (1994))、
トリ網膜(Godbout, R., Exp. Eye Res., 56, 95-106(19
93))、ＦＡＢＰをコードする遺伝子と８１−８６％相同
性を示した。また推定された産物は、ヒト骨格筋ＦＡＢ
Ｐ(Peeters, R. A., etal., Biochem. J., 276, 203-20
7(1991))と６５％、そしてヒトミエリン蛋白Ｐ２(Hayas
aka, K., et al., Biochem. Biophys. Res. Commun., 1
81(1), 204-207(1991))と５９％相同性を示した。ラッ
ト、マウス脳、やトリ網膜ＦＡＢＰと８７から９１％ア
ミノ酸配列の同一性を示した。The isolated gene was isolated from rat brain (Bennett, E., et al.) By homology search of FASTA program.
l., J. Neurochem., 63 , 1616-1624 (1994)), mouse brain
(Feng, L., et al., Neuron, 12 (4) 895-908 (1994)),
Avian retina (Godbout, R., Exp.Eye Res., 56 , 95-106 (19
93)), showing 81-86% homology with the gene encoding FABP. The estimated product is human skeletal muscle FAB.
P (Peeters, RA, etal., Biochem. J., 276 , 203-20
7 (1991)) and 65%, and human myelin protein P2 (Hayas
aka, K., et al., Biochem. Biophys. Res. Commun., 1
81 ( 1), 204-207 (1991)). It showed 87-91% amino acid sequence identity with rat, mouse brain and avian retina FABP.
【０１１３】ヒト筋ＦＡＢＰに関連する部位特異的突然
変異(Prinsen, C. F.M. and Veerkamp, J. H., Bioche
m. J., 314, 253-260 (1996))やクリオ・スタログラフ
ィー(Zanotti, G., et al., J. Biol. Chem., 267, 185
41-18550 (1992))により、Phe-17, Arg-107, Arg-127又
はTyr-129のアミノ酸がオレイン酸に結合する能力と重
要な役割を演じることを示している。これらのアミノ酸
は他の種のＦＡＢＰと同様にヒト脳ＦＡＢＰにおいても
厳格に保存されている。Site-specific mutations associated with human muscle FABP (Prinsen, CFM and Veerkamp, JH, Bioche
m. J., 314 , 253-260 (1996)) and cryo stalography (Zanotti, G., et al., J. Biol. Chem., 267 , 185).
41-18550 (1992)) show that Phe-17, Arg-107, Arg-127 or Tyr-129 amino acids play an important role in the ability to bind oleic acid. These amino acids are strictly conserved in human brain FABPs as well as other species of FABPs.
【０１１４】（２）ノーザンブロット分析 正常ヒト成人組織におけるヒト脳ＦＡＢＰｍＲＮＡの発
現を、ＧＥＮ−１２８Ｂ１０ｃＤＮＡクローンの３’非
翻訳領域に相当する部位をＰＣＲにより増幅し、該ＰＣ
Ｒ産物を精製し、［32Ｐ］−ｄＣＴＰ（ランダムプライ
ムドＤＮＡラベリングキット、ベーリンガーマンハイム
社）により標識してプローブとし、実施例１−（２）に
準じてノーザンブロッティングを行なった。(2) Northern blot analysis The expression of human brain FABP mRNA in normal human adult tissues was determined by amplifying a site corresponding to the 3 'untranslated region of the GEN-128B10 cDNA clone by PCR, and
The R product was purified and labeled with [ 32 P] -dCTP (random primed DNA labeling kit, Boehringer Mannheim) to obtain a probe, and Northern blotting was performed according to Example 1- (2).
【０１１５】ノーザンブロット分析の結果、脳において
およそ１．２Kbの転写物と骨格筋において小さなｍＲＮ
Ａが検出されたが、試験した他の組織の心臓、胎盤、
肺、肝臓、腎臓及び膵臓では検出されなかった。骨格筋
に発現されたｍＲＮＡはＤＮＡシークエンスにより今回
単離された脳ＦＡＢＰｃＤＮＡと同一であることが示さ
れ、脳に発現されているｍＲＮＡより小分子の転写物が
骨格筋にも存在していることが判明した。さらにヒト胎
児脳において成人に比べ多量に発現されていることが判
明した。このことは、胎児脳においてＦＡＢＰが重要な
役割を果たしていることを伺わせるものである。加えて
トリ網膜ＦＡＢＰと同じく、マウスとラット脳ＦＡＢＰ
ｓはそれぞれ組織発達の早期段階で必要であると考えら
れており、それはヒト脳も同様に胎生期の期間中ＦＡＢ
Ｐが必要と考えられる。The results of Northern blot analysis showed that the transcript of approximately 1.2 Kb in the brain and small mRN in skeletal muscle.
A was detected, but the heart, placenta,
It was not detected in lung, liver, kidney and pancreas. DNA sequence shows that mRNA expressed in skeletal muscle is identical to brain FABP cDNA isolated this time, and transcripts of smaller molecules than mRNA expressed in brain are also present in skeletal muscle. There was found. Furthermore, it was found that the expression was higher in human fetal brain than in adults. This suggests that FABP plays an important role in fetal brain. In addition, mouse and rat brain FABP as well as avian retinal FABP
s are each thought to be required at an early stage of tissue development, which indicates that the human brain also has FAB during fetal life.
P is considered necessary.
【０１１６】本発明ヒト脳ＦＡＢＰ遺伝子は、ヒト脳Ｆ
ＡＢＰ蛋白の発現及び検出に利用でき、かくして該蛋白
の関与する各種の疾患の診断、病態解明、例えば、脳発
育不全、神経性疾患等の各種疾患の診断等を行なうこと
ができ、また上記疾患の治療及び予防薬のスクリーニン
グや評価に利用できる。The human brain FABP gene of the present invention
It can be used for the expression and detection of ABP protein, and thus can diagnose various diseases involving the protein, elucidate the condition of the disease, for example, diagnose various diseases such as cerebral dysfunction, neurological disease, etc. It can be used for screening and evaluation of therapeutic and prophylactic drugs.
【０１１７】[0117]
【実施例４】ＳＲＥ−ＺＢＰ関連ジンクフィンガー遺伝
子 （１）ＳＲＥ−ＺＢＰ関連ジンクフィンガー遺伝子のク
ローニング及びＤＮＡシークエンシング ｃ−ｆｏｓ遺伝子の５’上流域に存在する血清反応エレ
メント(ＳＲＥ)は、核蛋白であるｃ−ｆｏｓの転写を制
御する血清反応因子(ＳＲＦ)の標的結合部位である(Gil
man, M.Z., et al., Mol Cell Biol., 6, 4305-4316 (1
986); Norman,C., et al., Cell, 55, 989-1003(1988);
Kadonaga, J.T., et al., Cell, 51,1079-1090(198
7))。ｃ−ｆｏｓＳＲＥはプロテイン・カイネースＣに
対する反応(Gilman, M.Z., Genes Devel., 2, 394-402
(1988))と成長因子によって誘導される介在シグナル(Gr
eenberg, M.E., et al., Mol. Cell Biol., 6, 1050-10
57(1986))の為に必要である。加えてグルココルチコイ
ド・レセプターは、ｃ−ｆｏｓＳＲＥに対して結合し、
ｃ−ｆｏｓプロモーターの活性化を抑制することによっ
て、線維芽細胞の成長を抑制する(Karagianni, N. and
Tsawdaroglou, N., Oncogene, 9, 2327-2334(1994))。
これらの知見はＳＲＥが複数のＳＲＥ結合蛋白の標的と
なる多機能のエレメントであることを提言している。Example 4 SRE-ZBP-Related Zinc Finger Gene (1) Cloning and DNA Sequencing of SRE-ZBP-Related Zinc Finger Gene The serum reaction element (SRE) present in the 5 ′ upstream region of the c-fos gene is a nuclear protein Is a target binding site of serum response factor (SRF) that controls the transcription of c-fos (Gil
man, MZ, et al., Mol Cell Biol., 6 , 4305-4316 (1
986); Norman, C., et al., Cell, 55 , 989-1003 (1988);
Kadonaga, JT, et al., Cell, 51 , 1079-1090 (198
7)). c-fosSRE reacts with protein kinase C (Gilman, MZ, Genes Devel., 2 , 394-402)
(1988)) and an intervening signal (Gr
eenberg, ME, et al., Mol.Cell Biol., 6 , 1050-10
57 (1986)). In addition, the glucocorticoid receptor binds to c-fosSRE,
Suppress fibroblast growth by suppressing c-fos promoter activation (Karagianni, N. and
Tsawdaroglou, N., Oncogene, 9 , 2327-2334 (1994)).
These findings suggest that the SRE is a multifunctional element targeted by multiple SRE binding proteins.
【０１１８】ＳＲＥ−ＺＢＰ(血清反応エレメント結合
ジンクフィンガー蛋白:Attar, R.M.and Gilman, M.Z.,
Mol. Cell Biol., 12, 2432-2443(1992))は、クラペル
・タイプの保存された配列を含んでいるＣ2Ｈ2ジンクフ
ィンガー蛋白のファミリーのメンバーである。ＳＲＥ−
ＺＢＰのジンクフィンガー領域は、ｃ−ｆｏｓＳＲＥに
直接的に結合する(Rosenberg, U.B., et al., Nature,
319, 336-339(1986))。ジンクフィンガー・モチーフは
当初アフリカツメガエルの転写因子IIIAのアミノ酸配列
内で同定された(Miller, J. et al., EMBO J., 4, 1609
-1614(1985))、このループ様のモチーフは、亜鉛イオン
を持つシスティンとヒスチジンの２つのペアの相互作用
によって形作られており、そしてＲＮＡと／或はＤＮＡ
分子に結合することによって転写を制御すると考えられ
ている(Kadonaga, J.T., et al.,Cell, 51, 1079-1090
(1987); Stanojevic, D., et al., Nature, 3 41, 331-3
35(1989))。本発明者らは、ＳＲＥ−ＺＢＰに対する相
同物であると推定される新規なヒトジンクフィンガー遺
伝子の単離と染色体座位を報告する。SRE-ZBP (Serum reaction element binding zinc finger protein: Attar, RMand Gilman, MZ,
Mol. Cell Biol., 12, 2432-2443 (1992)) is a member of a family of C 2 H 2 zinc finger proteins that contain conserved sequences Kuraperu type. SRE-
The zinc finger region of ZBP binds directly to c-fosSRE (Rosenberg, UB, et al., Nature,
319 , 336-339 (1986)). The zinc finger motif was originally identified within the amino acid sequence of Xenopus transcription factor IIIA (Miller, J. et al., EMBO J., 4 , 1609).
-1614 (1985)), this loop-like motif is formed by the interaction of two pairs of cystine and histidine with zinc ions, and RNA and / or DNA
It is thought to regulate transcription by binding to molecules (Kadonaga, JT, et al., Cell, 51 , 1079-1090
(1987); Stanojevic, D., et al., Nature, 3 41 , 331-3.
35 (1989)). We report the isolation and chromosomal locus of a novel human zinc finger gene putatively homologous to SRE-ZBP.
【０１１９】実施例１−（１）と同様の方法でヒト胎児
脳ｃＤＮＡライブラリーから任意に選択したｃＤＮＡク
ローンの配列と公知の遺伝子とのホモロジーをデータ・
ベースの検索によって比較した。その経過において、本
発明者らは、ｃ−ｆｏｓ血清反応エレメントに結合する
蛋白であるＳＲＥ−ＺＢＰをコードする遺伝子に対して
核酸配列において６５．２％の同一性を呈した１つのク
ローンを見つけ、該クローンをＧＥＮ−５０６Ｇ１０と
命名した。該クローンは５’と３’末端配列が欠けてい
たので、本発明者らは前記で得られたｃＤＮＡクローン
を[32Ｐ]ランダムプライミング法により標識し、これを
プローブとして、ヒト膵臓のｍＲＮＡから構築されたｃ
ＤＮＡライブラリー(ＺＡＰ ＥｘｐｒｅｓｓTMＥｃｏ
ＲＩ／ＸｈｏｌｃＤＮＡライブラリー；ストラトジーン
社製)に対してスクリーニングした。得られたクローン
のＤＮＡ配列をＡＢＩ ＰＲＩＳＭTM３７７自動ＤＮＡ
シークエンサーで配列決定した。The homology between the sequence of a cDNA clone arbitrarily selected from a human fetal brain cDNA library and a known gene in the same manner as in Example 1- (1) was
Compared by base search. In the course of this, we found one clone that exhibited 65.2% identity in nucleic acid sequence to the gene encoding SRE-ZBP, a protein that binds to the c-fos serum response element. The clone was named GEN-506G10. Since the clone lacked the 5 ′ and 3 ′ terminal sequences, the present inventors labeled the cDNA clone obtained above by the [ 32 P] random priming method and used it as a probe to obtain mRNA from human pancreas. Constructed c
DNA library (ZAP Express ™ Eco
(RI / Xhol cDNA library; manufactured by Stratogene). The DNA sequence of the resulting clone was converted to ABI PRISM ™ 377 automated DNA.
Sequenced on a sequencer.
【０１２０】上記方法によって、本発明者らは２つのｃ
ＤＮＡクローンを得、５’非翻訳領域が１７１塩基で、
３’非翻訳領域が２９０塩基であって、５６２アミノ酸
をコードする１６８６塩基の蛋白質翻訳領域を含んでい
るクローンをＧＥＮ−５０６Ｇ１０−ａと命名した。According to the above method, the present inventors have found that two c
A DNA clone was obtained and the 5 'untranslated region was 171 bases,
A clone having a 3 'untranslated region of 290 bases and containing a protein translation region of 1686 bases encoding 562 amino acids was named GEN-506G10-a.
【０１２１】ＧＥＮ−５０６Ｇ１０−ａ遺伝子につい
て、配列番号：１５に２１６８塩基の核酸配列からなる
全配列、配列番号：１４に１６８３塩基のオープン・リ
ーディング・フレームを含む核酸配列並びに配列番号：
１３に該核酸配列でコードされる５６１アミノ酸の推定
アミノ酸配列を示す。Regarding the GEN-506G10-a gene, SEQ ID NO: 15 has the entire sequence consisting of a nucleic acid sequence of 2168 bases, SEQ ID NO: 14 has the nucleic acid sequence containing an open reading frame of 1683 bases, and SEQ ID NO: 14.
13 shows the deduced amino acid sequence of 561 amino acids encoded by the nucleic acid sequence.
【０１２２】開始コドンは、配列番号：１５の塩基配列
番号の１７２−１７４番目であり、１８３６−１８３８
番目が終始コドンを示していた。The start codon is at positions 172-174 of the base sequence number of SEQ ID NO: 15, and is 1836-1838.
The third indicated a codon throughout.
【０１２３】ＧＥＮ−５０６Ｇ１０−ａ遺伝子に存在す
るポリＡテイルを続ける可能性をもつポリアデニレーシ
ョン・シグナルが、終始コドンから２６１塩基下流に見
られた。推定された産物はＳＲＥ−ＺＢＰに対して６７
％の相同性が明らかになった。モチーフ・ライブラリー
ＰＲＯＳＩＴＥ(Bairoch, A., Nucleic Acids Res.,20,
2013-2018(1992))を使用するＭｏｔｉｆＦｉｎｄｅｒ
プログラムでの分析は、推定されたＧＥＮ−５０６Ｇ１
０−ａ蛋白がＣＸ2ＣＸ3ＦＸ5ＬＸ2ＨＸ3Ｈの共通配列
を持つＡＴＰ／ＧＴＰ結合部位モチーフ(Ｐループ)と７
つのＣ2Ｈ2ジンクフィンガー領域を保有することを指摘
した。A polyadenylation signal with the potential to continue the poly A tail present in the GEN-506G10-a gene was found 261 bases downstream from the stop codon. The estimated product was 67 against SRE-ZBP.
% Homology was revealed. Motif Library PROSITE (Bairoch, A., Nucleic Acids Res., 20 ,
2013-2018 (1992)) MotifFinder
The analysis in the program is based on the estimated GEN-506G1
0-a protein has an ATP / GTP binding site motif (P loop) having a common sequence of CX 2 CX 3 FX 5 LX 2 HX 3 H and 7
It was noted that it possessed two C 2 H 2 zinc finger regions.
【０１２４】もう一方のｃＤＮＡクローンは、ＧＥＮ−
５０６Ｇ１０−ｂと命名され、該クローンは、５’非翻
訳領域が１５７塩基で、３’非翻訳領域が２６５塩基で
ある２０１アミノ酸をコードする６０３塩基のオープン
・リーディング・フレームを含んでいた。The other cDNA clone was GEN-
Designated as 506G10-b, the clone contained a 603 base open reading frame encoding 201 amino acids with a 5 'untranslated region of 157 bases and a 3' untranslated region of 265 bases.
【０１２５】ＧＥＮ−５０６Ｇ１０−ｂ遺伝子につい
て、配列番号：１８に１０５１塩基の核酸配列からなる
全配列、配列番号：１７に６０３塩基のオープン・リー
ディング・フレームを含む核酸配列並びに配列番号：１
６に該核酸配列でコードされる２０１アミノ酸の推定ア
ミノ酸配列を示す。Regarding the GEN-506G10-b gene, SEQ ID NO: 18 shows the entire sequence consisting of a nucleic acid sequence of 1051 bases, SEQ ID NO: 17 shows the nucleic acid sequence containing an open reading frame of 603 bases, and SEQ ID NO: 1.
6 shows the predicted amino acid sequence of 201 amino acids encoded by the nucleic acid sequence.
【０１２６】ＧＥＮ−５０６Ｇ１０−ｂ遺伝子にあるポ
リＡテイルを続ける可能性をもつポリアデニレーション
・シグナルが、終始コドンから２４７塩基下流に見られ
た。A polyadenylation signal with the potential to continue the poly A tail at the GEN-506G10-b gene was found 247 bases downstream from the stop codon.
【０１２７】このｃＤＮＡによって推定された蛋白は、
ＡＴＰ−ＧＴＰ結合部位と７つのＣ2Ｈ2ジンクフィンガ
ー領域のどちらも含んでいなかった。２つのｃＤＮＡの
３’非翻訳領域は同じコスミドクローンに含まれている
ことが確認されたので、本発明者らは２つのタイプの転
写物が二者択一的なスプライシングによって産生された
と考えた。両クローンは、ＳＲＥ−ＺＢＰの５’領域に
対して塩基配列で６５％とアミノ酸配列で６７％の同一
性を明らかした。より大きなｃＤＮＡによって推定され
た蛋白のジンクフィンガー領域は、ｃ−ｆｏｓ血清反応
エレメントに直接結合する分子であるＳＲＥ−ＺＢＰの
それらに対して５４％の相同性を示した。The protein deduced from this cDNA is
Both ATP-GTP binding site and seven C 2 H 2 zinc finger region did not contain. Since it was confirmed that the 3 'untranslated regions of the two cDNAs were contained in the same cosmid clone, we considered that two types of transcripts were produced by alternative splicing. . Both clones revealed 65% nucleotide sequence identity and 67% amino acid sequence identity to the 5 'region of SRE-ZBP. The zinc finger region of the protein, deduced by the larger cDNA, showed 54% homology to those of SRE-ZBP, a molecule that directly binds to the c-fos serum response element.
【０１２８】（２）ノーザンブロット分析 正常ヒト組織におけるＧＥＮ−５０６Ｇ１０−ａｍＲＮ
Ａの発現を実施例１−（２）と同様にして、ランダム・
オリゴヌクレオチド・プライミング法によって標識した
ヒトｃＤＮＡクローンをプローブとするノーザンブロッ
トにより評価した。(2) Northern blot analysis GEN-506G10-amRN in normal human tissues
The expression of A was determined in the same manner as in Example 1- (2).
Evaluation was performed by Northern blot using a human cDNA clone labeled by the oligonucleotide priming method as a probe.
【０１２９】ノーザンブロット分析は、製品使用法に従
い、ヒトＭＴＮブロット（Human Multiple Tissue Noth
ern blot ; クローンテック社製、パロ・アルト、カリ
フォルニア、米国）を用いて実施した。[0129] Northern blot analysis was performed according to the product usage according to human MTN blot (Human Multiple Tissue Noth).
ern blot; Clonetech, Palo Alto, California, USA).
【０１３０】即ち、上記ジンクフィンガー領域を含むＧ
ＥＮ−５０６Ｇ１０ｃＤＮＡクローンのＰＣＲ増幅産物
を［32Ｐ］−ｄＣＴＰランダムプライムドＤＮＡラベリ
ングキット（ベーリンガーマンハイム社）により標識し
てプローブとした。That is, G containing the above zinc finger region
The PCR amplification product of the EN-506G10 cDNA clone was labeled with a [ 32 P] -dCTP random primed DNA labeling kit (Boehringer Mannheim) to obtain a probe.
【０１３１】ブロッティングメンブランは、４２℃で一
晩、５０％ホルムアミド／５×ＳＳＰＥ／１０×デンハ
ルツ溶液／２％ＳＤＳ溶液（１００μｇ／ｍｌ変性サケ
***ＤＮＡ含有）溶液中でハイブリダイズされた。２×
ＳＳＣ／０．０１％ＳＤＳにて室温下にて２回洗浄後、
次いで０．１×ＳＳＣ／０．０５％ＳＤＳにて５０℃下
に４０分間で１回洗浄した。メンブランは−７０℃下に
１８時間、Ｘ線フィルム(コダック社製)に対して露光し
た。The blotting membrane was hybridized at 42 ° C. overnight in a 50% formamide / 5 × SSPE / 10 × Denhartz solution / 2% SDS solution (containing 100 μg / ml denatured salmon sperm DNA). 2x
After washing twice with SSC / 0.01% SDS at room temperature,
Then, the plate was washed once with 0.1 × SSC / 0.05% SDS at 50 ° C. for 40 minutes. The membrane was exposed to an X-ray film (manufactured by Kodak) at -70 ° C for 18 hours.
【０１３２】その結果、２．３ｋｂの転写物が試験した
全てのヒト組織内に発現していることが明らかとなっ
た。加えて、１．３ｋｂの転写物が心臓、脳、胎盤及び
肺に特異的に観察された。小さな転写物はおそらくＧＥ
Ｎ−５０６Ｇ１０−ａの３’部分が欠失したＧＥＮ−５
０６Ｇ１０−ｂに相同していると考えられた。As a result, it was clarified that the 2.3 kb transcript was expressed in all the human tissues tested. In addition, a 1.3 kb transcript was specifically observed in heart, brain, placenta and lung. Small transcripts are probably GE
GEN-5 in which the 3 'portion of N-506G10-a has been deleted
It appeared to be homologous to 06G10-b.
【０１３３】（３）ＦＩＳＨによるコスミド・クローン
と染色体の局在 ＧＥＮ−５０６Ｇ１０遺伝子の染色体の局在を調べるた
めに実施例１−（３）と同様に、ＦＩＳＨによって染色
体の局在を調べた。(3) Localization of cosmid clones and chromosomes by FISH In order to investigate chromosome localization of the GEN-506G10 gene, chromosome localization was performed by FISH in the same manner as in Example 1- (3).
【０１３４】本発明者らは、ヒト膵臓ｃＤＮＡライブラ
リーから得られた前記のＧＥＮ−５０６Ｇ１０−ａｃＤ
ＮＡクローンを［32Ｐ］−ランダム標識してプローブと
して用い、正常ヒト染色体ＤＮＡから構築されたヒト・
コスミド・ライブラリーをスクリーニングした。その結
果、２つのコスミド・クローンを単離した。本発明者ら
は、新規な遺伝子の染色体の局在を決定するためにこれ
らの２つのコスミドの各々でＦＩＳＨ試験を実施した。The present inventors have determined that the above-mentioned GEN-506G10-acD obtained from a human pancreatic cDNA library.
The NA clone was [ 32 P] -randomly labeled and used as a probe to generate a human clone constructed from normal human chromosomal DNA.
The cosmid library was screened. As a result, two cosmid clones were isolated. We performed a FISH test on each of these two cosmids to determine the chromosomal localization of the novel gene.
【０１３５】１００のＲ−バンド染色体を試験し、２つ
の両クローンが第７染色体のバンドｑ２２．１−２２．
３上の位置で特にシグナルが明らかになることが分かっ
た。従ってＧＥＮ−５０６Ｇ１０は、７番目染色体、バ
ンドｑ２２．１−２２．３上にマップされた。The 100 R-band chromosomes were examined and two clones were found to have the chromosome 7 band q22.1-22.
It was found that a signal was particularly apparent at the position above 3. Thus, GEN-506G10 was mapped on chromosome 7, band q22.1-22.3.
【０１３６】上記の如く、本発明者らは、推定された産
物が血清反応エレメント結合蛋白、ＳＲＥ−ＺＢＰに対
する相同物である新規なジンクフィンガーｃＤＮＡの単
離と局在について記載した。しかしながら、ＳＲＥ−Ｚ
ＢＰはＳＲＦｓのような他のＳＲＥ結合蛋白と高い程度
の相同性を示さなかったが、そのジンクフィンガーモチ
ーフはｃ−ｆｏｓＳＲＥの３’部分に直接結合すること
が知られている(Atter, R.M. and Gilman, V.Z., Mol.
Cell Biol., 12, 2432-2443(1992))。というのは、ジン
クフィンガーモチーフは、アフリカツメガエルの転写因
子IIIAで当初同定され、数百のＣ2Ｈ2ジンクフィンガー
蛋白が単離されている(Becker, K.G., et al., Hum. Mo
l. Genet., 4, 685-691(1994))。これらの蛋白は、ＲＮ
Ａと、又はＤＮＡに結合することによって転写を制御す
ると考えられている。As described above, the present inventors have described the isolation and localization of a novel zinc finger cDNA whose putative product is a homolog of the serum response element binding protein, SRE-ZBP. However, SRE-Z
Although BP did not show a high degree of homology with other SRE binding proteins such as SRFs, its zinc finger motif is known to bind directly to the 3 'portion of c-fosSRE (Atter, RM and Gilman, VZ, Mol.
Cell Biol., 12 , 2432-2443 (1992)). The zinc finger motif was originally identified in Xenopus transcription factor IIIA, and hundreds of C 2 H 2 zinc finger proteins have been isolated (Becker, KG, et al., Hum. Mo.
l. Genet., 4 , 685-691 (1994)). These proteins are RN
It is believed that transcription is controlled by binding to A or to DNA.
【０１３７】推定された蛋白は７つのうちの６つがＣＸ
2ＣＸ3ＦＸ5ＬＸ2ＨＸ3Ｈの共通配列からなる７つのＣ2
Ｈ2ジンクフィンガー領域を保有することが報告されて
いる。共通配列「Ｈ2／Ｃ2」リンクによってつなげられ
た４つは、ＴＧＥＫＰＹＸ配列である(Becker, K.G., e
t al., Hum. Mol. Genet., 4, 685-691(1994))。[0137] Six of the seven estimated proteins were CX.
7 C 2 consisting of a common sequence of 2 CX 3 FX 5 LX 2 HX 3 H
To possess of H 2 zinc finger region has been reported. Four, which are linked by a common sequence "H 2 / C 2" link is TGEKPYX sequence (Becker, KG, e
tal., Hum. Mol. Genet., 4 , 685-691 (1994)).
【０１３８】ノーザンブロット分析より、確認された
２．３ｋｂ転写物によって推定された蛋白のジンクフィ
ンガー領域が、ＭＭＺＦＰＲ、ＨＳＨＦ、ＨＵＭＺＮＦ
７及びＲＮＵ２７１８６のような他のジンクフィンガー
蛋白のそれらに対して４８−５７％同一であることを明
らかにした。The zinc finger region of the protein deduced from the 2.3 kb transcript confirmed by Northern blot analysis was MMZFPR, HSHF, HUMZNF.
7 and 48-57% identical to those of other zinc finger proteins such as RNU27186.
【０１３９】ＭＭＺＦＰＲは、***形成の調整の役割を
持つと考えられているネズミの蛋白である(Burke, P.S.
and Wolgemuth, D.J., Nucl. Acids Res., 20, 2827-2
834(1992))。試験管内においてヒト・ミエロイド細胞株
の最終分化を誘導するＨＳＨＦは、おそらく細胞の分化
の過程に関連する(Pannute, A., et al., Nucl. Acids
Res., 16, 4227-4237(1988))。ＨＵＭＺＮＦ７も試験管
内おいてヒト・ミエロイド細胞株の最終分化を誘導する
かもしれない(Lania, L., et al., Genomics,6, 333-34
0(1990))。ラットのオリゴデンドロサイトに見つけられ
たＲＮＵ２７１８６は、ミエリン誘導グリア細胞内の配
列特異的転写の抑制物として作用する(Pott, U., et a
l., J. Neurochem., 65, 1955-1966(1995))。転写の抑
制物としてこれらの遺伝子産物の機能がショウジョウバ
エのクラッペル遺伝子のそれに対して類似しているので
(Licht, J.D., et al., Nature, 346, 76-79(1990))、
ＧＥＮ−５０６Ｇ１０−ａの産物は類似の役割を演じる
かもしれない。さらにこの推定された蛋白は、共通配列
Ａ／ＧＸ4ＧＫＳ／Ｔに相同するＡＴＰ／ＧＴＰ結合部
位を含んでいて、Ｐループと呼ばれている(Saraste,
M., et al., Trends Biochem. Sci., 15, 430-434(199
0))。ＡＴＰ或はＧＴＰとの結合を通して、この産物は
細胞内のシグナル伝達を促進しているようである。MMZFPR is a murine protein thought to have a role in regulating spermatogenesis (Burke, PS
and Wolgemuth, DJ, Nucl. Acids Res., 20 , 2827-2
834 (1992)). HSHF, which induces terminal differentiation of human myeloid cell lines in vitro, is probably involved in the process of cell differentiation (Pannute, A., et al., Nucl. Acids
Res., 16 , 4227-4237 (1988)). HUMZNF7 may also induce terminal differentiation of human myeloid cell lines in vitro (Lania, L., et al., Genomics, 6 , 333-34).
0 (1990)). RNU27186 found in rat oligodendrocytes acts as a repressor of sequence-specific transcription in myelin-induced glial cells (Pott, U., et a).
l., J. Neurochem., 65 , 1955-1966 (1995)). Because the function of these gene products as repressors of transcription is similar to that of the Drosophila kappel gene,
(Licht, JD, et al., Nature, 346 , 76-79 (1990)),
The product of GEN-506G10-a may play a similar role. Furthermore, this putative protein contains an ATP / GTP binding site homologous to the consensus sequence A / GX 4 GKS / T and is called the P loop (Saraste,
M., et al., Trends Biochem.Sci., 15 , 430-434 (199
0)). Through binding to ATP or GTP, this product appears to promote intracellular signaling.
【０１４０】本発明ヒトＳＲＥ−ＺＢＰ関連ジンクフィ
ンガー遺伝子は、ヒトＳＲＥ−ＺＢＰ関連ジンクフィン
ガー蛋白の発現及び検出に利用でき、かくして該蛋白の
関与する各種の疾患の診断、病態解明、例えば、悪性腫
瘍のような各種疾患の診断等を行なうことができ、また
上記疾患の治療及び予防薬のスクリーニングや評価に利
用できる。The human SRE-ZBP-related zinc finger gene of the present invention can be used for the expression and detection of human SRE-ZBP-related zinc finger protein. Thus, diagnosis and elucidation of various diseases involving the protein, for example, malignant tumors And the like, and can be used for screening and evaluation of therapeutic and prophylactic agents for the above-mentioned diseases.
【０１４１】[0141]
【実施例５】ヒトＮＭＬＹ６遺伝子 （１）ヒトＮＭＬＹ６遺伝子のクローニング及びＤＮＡ
シークエンシング 実施例１−（１）と同様の方法でヒト胎児脳ｃＤＮＡラ
イブラリーから任意に選択したｃＤＮＡクローンの配列
解析と公知の遺伝子とのホモロジーをデータ・ベースの
検索の結果、マウスＬｙ−６ファミリー蛋白質と高い相
同性を有するヒトＮＭＬＹ６遺伝子と考えられるアミノ
酸配列をコードするｃＤＮＡ配列を有するクローンを見
つけ、該クローンをＧＥＮ−４２５Ｇ０８と命名した。Example 5 Human NMLY6 gene (1) Cloning and DNA of human NMLY6 gene
Sequencing The sequence analysis of a cDNA clone arbitrarily selected from a human fetal brain cDNA library in the same manner as in Example 1- (1) and a homology with a known gene as a result of a database-based search revealed that mouse Ly-6 A clone having a cDNA sequence encoding an amino acid sequence considered to be a human NMLY6 gene having high homology to the family proteins was found, and the clone was named GEN-425G08.
【０１４２】上記で得られたクローンのｃＤＮＡ配列
は、ＡＢＩ ＰＲＩＳＭＴＭ３７７自動ＤＮＡシークエ
ンサーによる配列決定の結果、４４７塩基の推定アミノ
酸翻訳領域を含んでおり、これによってコードされるア
ミノ酸配列は、１４９アミノ酸残基を有し、全長ｃＤＮ
Ａクローンの核酸配列は、９０１塩基からなっていた。
その全配列は、配列番号：２１に示す通りであり、オー
プン・リーディング・フレームを含む核酸配列は配列番
号：２０に、該酸配列でコードされるアミノ酸の推定ア
ミノ酸配列は配列番号：１９に示す通りであった。The cDNA sequence of the clone obtained above contains a deduced amino acid translation region of 447 bases as a result of sequencing by an ABI PRISM ™ 377 automatic DNA sequencer, and the amino acid sequence encoded thereby has 149 amino acid residues. With full length cDN
The nucleic acid sequence of the A clone consisted of 901 bases.
The entire sequence is as shown in SEQ ID NO: 21, the nucleic acid sequence containing the open reading frame is shown in SEQ ID NO: 20, and the deduced amino acid sequence of the amino acid encoded by the acid sequence is shown in SEQ ID NO: 19 It was right.
【０１４３】他のＬｙ−６ファミリー蛋白質と本ヒトＮ
ＭＬＹ６とのアミノ酸配列を比較検討し、またアミノ酸
翻訳開始領域に保存されている塩基配列（Kozak,M., J.
Biol.Chem., 266, 19867-19870 (1991)）と該ヒトＮＭ
ＬＹ６遺伝子の５′領域の比較より決定された開始コド
ンは、配列番号：２４の塩基配列の２番号のＡＴＧトリ
プレットである１４７−１４９番目に位置していた。ま
た、ポリアデニレーション・シグナル（ＡＡＴＡＡＡ）
は、同塩基配列番号の８７９−８８４番目に位置してい
た。Other Ly-6 Family Proteins and the Human N
The amino acid sequence was compared with that of MLY6, and the nucleotide sequence conserved in the amino acid translation initiation region (Kozak, M., J. Am.
Biol. Chem., 266 , 19867-19870 (1991)) and the human NM.
The start codon determined by comparison of the 5 'region of the LY6 gene was located at positions 147 to 149, which is the ATG triplet of No. 2 in the nucleotide sequence of SEQ ID NO: 24. In addition, polyadenylation signal (AATAAA)
Was located at positions 879-884 of the same base sequence number.
【０１４４】（２）ノーザンブロット分析 正常ヒト組織におけるＧＥＮ−４２５Ｇ０８−ｍＲＮＡ
の発現を実施例１−（２）と同様にして、ランダム・オ
リゴヌクレオチド・プライミング法によって標識したヒ
トｃＤＮＡクローンをプローブとするノーザンブロット
により評価した。(2) Northern blot analysis GEN-425G08-mRNA in normal human tissues
Was evaluated by Northern blot using a human cDNA clone labeled by the random oligonucleotide priming method as a probe in the same manner as in Example 1- (2).
【０１４５】ノーザンブロット分析は、製品使用法に従
い、ヒトＭＴＮブロット（HumanMultiple Tissue Nothe
rn blot ; クローンテック社製、パロ・アルト、カリフ
ォルニア、米国）を用いて実施した。[0145] Northern blot analysis was performed according to the product usage according to the human MTN blot (Human Multiple Tissue No.
rn blot; Clonetech, Palo Alto, California, USA).
【０１４６】即ち、上記ＧＥＮ−４２５Ｇ０８ｃＤＮＡ
クローンのＰＣＲ増幅産物を［32Ｐ］−ｄＣＴＰ（ラン
ダムプライムドＤＮＡラベリングキット、ベーリンガー
マンハイム社）により標識してプローブとした。That is, the above-mentioned GEN-425G08 cDNA
The PCR amplification product of the clone was labeled with [ 32 P] -dCTP (random primed DNA labeling kit, Boehringer Mannheim) to obtain a probe.
【０１４７】ブロッティングは、６５℃で一晩、１Ｍ
ＮａＣｌ／５０ｍＭトリスＨＣｌ（ｐＨ７．５）／２×
デンハルツ溶液／１０％デキストランサルフェート／１
％ＳＤＳ溶液（１００μｇ／ｍｌ変性サケ***ＤＮＡ含
有）の溶液中でハイブリダイズした。２×ＳＳＣ／０．
１％ＳＤＳにて室温下にて２回洗浄後、次いで０．１×
ＳＳＣ／０．１％ＳＤＳにて６５℃下に４０分間で１回
洗浄した。フィルターは−７０℃下に１８時間、Ｘ線フ
ィルム(コダック社製)に対して露光した。Blotting was performed at 65 ° C. overnight with 1M
NaCl / 50 mM Tris HCl (pH 7.5) / 2 ×
Denhardt's solution / 10% dextran sulfate / 1
Hybridization was carried out in a solution of a% SDS solution (containing 100 μg / ml denatured salmon sperm DNA). 2 × SSC / 0.
After washing twice with 1% SDS at room temperature, then 0.1 ×
The plate was washed once with SSC / 0.1% SDS at 65 ° C. for 40 minutes. The filter was exposed to an X-ray film (manufactured by Kodak) at -70 ° C for 18 hours.
【０１４８】その結果、約１ｋｂの転写体が試験した全
て（１６）のヒト成人組織内に発現していることが明ら
かとなった。As a result, it was revealed that a transcript of about 1 kb was expressed in all (16) human adult tissues tested.
【０１４９】（３）ＦＩＳＨによるコスミド・クローン
と染色体の局在 ＧＥＮ−４２５Ｇ０８遺伝子の染色体の局在を調べるた
めに実施例１−（３）と同様に、ＦＩＳＨによって染色
体の局在を調べた。(3) Localization of cosmid clones and chromosomes by FISH To examine the chromosome localization of the GEN-425G08 gene, the chromosome localization was examined by FISH as in Example 1- (3).
【０１５０】その結果、ヒトＮＭＬＹ６遺伝子は、第８
染色体のバンドｑ２４．３上に位置することが分かっ
た。即ちＧＥＮ−４２５Ｇ０８は、染色体バンド８ｑ２
４．３上にマップされた。As a result, the human NMLY6 gene
It was found to be located on chromosome band q24.3. That is, GEN-425G08 is chromosome band 8q2
4.3 Mapped to above.
【０１５１】Ｌｙ−６ファミリーに属する蛋白質に対す
る抗体は、遺伝子治療のターゲットとなる血液幹細胞の
精製（van de Rijn, M., et al., proc.Natl.Acad.Sc
i., USA., 86, 4634-4638 (1989)）、血液細胞の分化の
研究（van de Rijn, M., et al., proc.Natl.Acad.Sc
i., USA., 8 6, 4634-4638 (1989); Classon, B.J. and
Coverdale, L., Proc.Natl.Acad.Sci., USA., 91, 5296
-5300 (1994)）、免疫細胞の活性化（Malek, T.R., et
al., J.Exp.Med., 164, 709-722 (1986)）、活性型免疫
細胞の産生抑制（Haque,A., et al., Immunology, 69,
558-563 (1990)）等に利用されており、また、抗腫瘍効
果も認められている（Lu, L., et al., J.Immunol., 14
2, 719-725 (1989)）。本実施例により提供されるヒト
ＮＭＬＹ６遺伝子の利用によれば、該遺伝子の各組織で
の発現の検出や、ヒトＮＭＬＹ６蛋白の遺伝子工学的製
造及びそれを用いた抗体の作成が可能となり、これによ
り、上記のような血液幹細胞の精製、血液細胞の分化の
研究、免疫細胞の活性化、免疫細胞の活性化の抑制、腫
瘍の治療等が可能となる。また、ヒトＮＭＬＹ６蛋白を
ターゲットとした化合物のスクリーニングも可能とな
り、かくして得られる化合物には、抗ヒトＮＭＬＹ６蛋
白抗体と同様の有用性がある。Antibodies against proteins belonging to the Ly-6 family were purified from blood stem cells as targets for gene therapy (van de Rijn, M., et al., Proc. Natl. Acad. Sc.
i., USA., 86 , 4634-4638 (1989)), studies on the differentiation of blood cells (van de Rijn, M., et al., proc. Natl. Acad. Sc.
.. i, USA, 8 6 , 4634-4638 (1989); Classon, BJ and
Coverdale, L., Proc. Natl. Acad. Sci., USA., 91 , 5296
-5300 (1994)), activation of immune cells (Malek, TR, et.
al., J. Exp. Med., 164 , 709-722 (1986)), suppression of production of activated immune cells (Haque, A., et al., Immunology, 69 ,
558-563 (1990)), and also has an antitumor effect (Lu, L., et al., J. Immunol., 14
2 , 719-725 (1989)). According to the use of the human NMLY6 gene provided by this example, it is possible to detect the expression of the gene in each tissue, to produce the human NMLY6 protein by genetic engineering, and to prepare an antibody using the same. Thus, purification of blood stem cells as described above, study of blood cell differentiation, activation of immune cells, suppression of activation of immune cells, treatment of tumors, and the like can be performed. In addition, screening of compounds targeting human NMLY6 protein is also possible, and the compounds thus obtained have the same utility as anti-human NMLY6 protein antibodies.
【０１５２】[0152]
【０１５３】配列番号：１ 配列の長さ：２０３ 配列の型：アミノ酸 トポロジー：直線状 配列の種類：蛋白 配列： Met Gly Ser Arg Asp His Leu Phe Lys Val Leu Val Val Gly Asp Ala 1 5 10 15 Ala Val Gly Lys Thr Ser Leu Val Gln Arg Tyr Ser Gln Asp Ser Phe 20 25 30 Ser Lys His Tyr Lys Ser Thr Val Gly Val Asp Phe Ala Leu Lys Val 35 40 45 Leu Gln Trp Ser Asp Tyr Glu Ile Val Arg Leu Gln Leu Trp Asp Ile 50 55 60 Ala Gly Gln Glu Arg Phe Thr Ser Met Thr Arg Leu Tyr Tyr Arg Asp 65 70 75 80 Ala Ser Ala Cys Val Ile Met Phe Asp Val Thr Asn Ala Thr Thr Phe 85 90 95 Ser Asn Ser Gln Arg Trp Lys Gln Asp Leu Asp Ser Lys Leu Thr Leu 100 105 110 Pro Asn Gly Glu Pro Val Pro Cys Leu Leu Leu Ala Asn Lys Cys Asp 115 120 125 Leu Ser Pro Trp Ala Val Ser Arg Asp Gln Ile Asp Arg Phe Ser Lys 130 135 140 Glu Asn Gly Phe Thr Gly Trp Thr Glu Thr Ser Val Lys Glu Asn Lys 145 150 155 160 Asn Ile Asn Glu Ala Met Arg Val Leu Ile Glu Lys Met Met Arg Asn 165 170 175 Ser Thr Glu Asp Ile Met Ser Leu Ser Thr Gln Gly Asp Tyr Ile Asn 180 185 190 Leu Gln Thr Lys Ser Ser Ser Trp Ser Cys Cys 195 200 SEQ ID NO: 1 Sequence length: 203 Sequence type: Amino acid Topology: Linear Sequence type: Protein Sequence: Met Gly Ser Arg Asp His Leu Phe Lys Val Leu Val Val Gly Asp Ala 1 5 10 15 Ala Val Gly Lys Thr Ser Leu Val Gln Arg Tyr Ser Gln Asp Ser Phe 20 25 30 Ser Lys His Tyr Lys Ser Thr Val Gly Val Asp Phe Ala Leu Lys Val 35 40 45 Leu Gln Trp Ser Asp Tyr Glu Ile Val Arg Leu Gln Leu Trp Asp Ile 50 55 60 Ala Gly Gln Glu Arg Phe Thr Ser Met Thr Arg Leu Tyr Tyr Arg Asp 65 70 75 80 Ala Ser Ala Cys Val Ile Met Phe Asp Val Thr Asn Ala Thr Thr Phe 85 90 95 Ser Asn Ser Gln Arg Trp Lys Gln Asp Leu Asp Ser Lys Leu Thr Leu 100 105 110 Pro Asn Gly Glu Pro Val Pro Cys Leu Leu Leu Ala Asn Lys Cys Asp 115 120 125 Leu Ser Pro Trp Ala Val Ser Arg Asp Gln Ile Asp Arg Phe Ser Lys 130 135 140 Glu Asn Gly Phe Thr Gly Trp Thr Glu Thr Ser Val Lys Glu Asn Lys 145 150 155 160 Asn Ile Asn Glu Ala Met Arg Val Leu Ile Glu Lys Met Met Met Arg Asn 165 170 175 Ser Thr Glu Asp I le Met Ser Leu Ser Thr Gln Gly Asp Tyr Ile Asn 180 185 190 Leu Gln Thr Lys Ser Ser Ser Trp Ser Cys Cys 195 200
【０１５４】配列番号：２ 配列の長さ：６０９ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列： ATGGGCAGCC GCGACCACCT GTTCAAAGTG CTGGTGGTGG GGGACGCCGC AGTGGGCAAG 60 ACGTCGCTGG TGCAGCGATA TTCCCAGGAC AGCTTCAGCA AACACTACAA GTCCACGGTG 120 GGAGTGGATT TTGCTCTGAA GGTTCTCCAG TGGTCTGACT ACGAGATAGT GCGGCTTCAG 180 CTGTGGGATA TTGCAGGGCA GGAGCGCTTC ACCTCTATGA CACGATTGTA TTATCGGGAT 240 GCCTCTGCCT GTGTTATTAT GTTTGACGTT ACCAATGCCA CTACCTTCAG CAACAGCCAG 300 AGGTGGAAAC AGGACCTAGA CAGCAAGCTC ACACTACCCA ATGGAGAGCC GGTGCCCTGC 360 CTGCTCTTGG CCAACAAGTG TGATCTGTCC CCTTGGGCAG TGAGCCGGGA CCAGATTGAC 420 CGGTTCAGTA AAGAGAACGG TTTCACAGGT TGGACAGAAA CATCAGTCAA GGAGAACAAA 480 AATATTAATG AGGCTATGAG AGTCCTCATT GAAAAGATGA TGAGAAATTC CACAGAAGAT 540 ATCATGTCTT TGTCCACCCA AGGGGACTAC ATCAATCTAC AAACCAAGTC CTCCAGCTGG 600 TCCTGCTGC 609SEQ ID NO: 2 Sequence length: 609 Sequence type: nucleic acid Number of strands: single strand Topology: linear Sequence type: DNA (cDNA) Sequence: ATGGGCAGCC GCGACCACCT GTTCAAAGTG CTGGTGGTGG GGGACGCCGC AGTGGGCAAG 60 ACGTCGCTGG TGCAGCGATA TTTTCCCAGGAGCT AACACTACAA GTCCACGGTG 120 GGAGTGGATT TTGCTCTGAA GGTTCTCCAG TGGTCTGACT ACGAGATAGT GCGGCTTCAG 180 CTGTGGGATA TTGCAGGGCA GGAGCGCTTC ACCTCTATGA CACGATTGTA TTATCGGGAT 240 GCCTCTGCCT GTGTTATTAT GTTTGACGTT ACCAATGCCA CTACCTTCAG CAACAGCCAG 300 AGGTGGAAAC AGGACCTAGA CAGCAAGCTC ACACTACCCA ATGGAGAGCC GGTGCCCTGC 360 CTGCTCTTGG CCAACAAGTG TGATCTGTCC CCTTGGGCAG TGAGCCGGGA CCAGATTGAC 420 CGGTTCAGTA AAGAGAACGG TTTCACAGGT TGGACAGAAA CATCAGTCAA GGAGAACAAA 480 AATATTAATG AGGCTATGAG AGTCCTCATT GAAAAGATGA TGAGAAATTC CACAGAAGAT 540 ATCATGTCTT TGTCCACCCA AGGGGACTAC ATCAATCTAC AAACCAAGTC CTCCAGCTGG 600 TCCTGCTGC 609
【０１５５】配列番号：３ 配列の長さ：２４４３ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列の特徴： 特徴を表わす記号：CDS 存在位置：４１．．６４９ 特徴を決定した方法：Ｅ 配列： CCACACTTCC CGCCTCCCTA AAACGCACAC CCCGCTAGCC ATG GGC AGC CGC GAC 55 Met Gly Ser Arg Asp 1 5 CAC CTG TTC AAA GTG CTG GTG GTG GGG GAC GCC GCA GTG GGC AAG ACG 103 His Leu Phe Lys Val Leu Val Val Gly Asp Ala Ala Val Gly Lys Thr 10 15 20 TCG CTG GTG CAG CGA TAT TCC CAG GAC AGC TTC AGC AAA CAC TAC AAG 151 Ser Leu Val Gln Arg Tyr Ser Gln Asp Ser Phe Ser Lys His Tyr Lys 25 30 35 TCC ACG GTG GGA GTG GAT TTT GCT CTG AAG GTT CTC CAG TGG TCT GAC 199 Ser Thr Val Gly Val Asp Phe Ala Leu Lys Val LeuGln Trp Ser Asp 40 45 50 TAC GAG ATA GTG CGG CTT CAG CTG TGG GAT ATT GCA GGG CAG GAG CGC 247 Tyr Glu Ile Val Arg Leu Gln Leu Trp Asp Ile Ala Gly Gln Glu Arg 55 60 65 TTC ACC TCT ATG ACA CGA TTG TAT TAT CGG GAT GCC TCT GCC TGT GTT 295 Phe Thr Ser Met Thr Arg Leu Tyr Tyr Arg Asp Ala Ser Ala Cys Val 70 75 80 85 ATT ATG TTT GAC GTT ACC AAT GCC ACT ACC TTC AGC AAC AGC CAG AGG 343 Ile Met Phe Asp Val Thr Asn Ala Thr Thr Phe Ser Asn Ser Gln Arg 90 95 100 TGG AAA CAG GAC CTA GAC AGC AAG CTC ACA CTA CCC AAT GGA GAG CCG 391 Trp Lys Gln Asp Leu Asp Ser Lys Leu Thr Leu Pro Asn Gly Glu Pro 105 110 115 GTG CCC TGC CTG CTC TTG GCC AAC AAG TGT GAT CTG TCC CCT TGG GCA 439 Val Pro Cys Leu Leu Leu Ala Asn Lys Cys Asp Leu Ser Pro Trp Ala 120 125 130 GTG AGC CGG GAC CAG ATT GAC CGG TTC AGT AAA GAG AAC GGT TTC ACA 487 Val Ser Arg Asp Gln Ile Asp Arg Phe Ser Lys Glu Asn Gly Phe Thr 135 140 145 GGT TGG ACA GAA ACA TCA GTC AAG GAG AAC AAA AAT ATT AAT GAG GCT 535 Gly Trp Thr Glu Thr Ser Val Lys Glu Asn Lys Asn Ile Asn Glu Ala 150 155 160 165 ATG AGA GTC CTC ATT GAA AAG ATG ATG AGA AAT TCC ACA GAA GAT ATC 583 Met Arg Val Leu Ile Glu Lys Met Met Arg Asn Ser Thr Glu Asp Ile 170 175 180 ATG TCT TTG TCC ACC CAA GGG GAC TAC ATC AAT CTA CAA ACC AAG TCC 631 Met Ser Leu Ser Thr Gln Gly Asp Tyr Ile Asn Leu Gln Thr Lys Ser 185 190 195 TCC AGC TGG TCC TGC TGC TAGTAGTGTT TGGCTTATTT TCCATCCCAG 679 Ser Ser Trp Ser Cys Cys 200 TTCTGGGAGG TCTTTTAAGT CTCTTCCCTT TGGTTGCCCA CCTGACCATT TTATTAAGTA 739 CATTTGAATT GTCTCCTGAC TACTGTCCAG TAAGGAGGCC CATTGTCACT TAGAAAAGAC 799 ACCTGGAACC CATGTGCATT TCTGCATCTC CTGGATTAGC CTTTCACATG TTGCTGACTC 859 ACATTAGTGC CAGTTAGTGC CTTCGGTGTA AGATCTTCTC ATCAGCCCTC AATTTGTGAT 919 CCGGAATTTT GTGAGAAGGA TTAGAAATCA GCACCTGCGT TTTAGAGATC ATAATTCTCA 979 CCTACTTCTG AGCTTATTTT TCCATTTGAT ATTCATTGAT ATCATGACTT CCAATTGAGA 1039 GGAAAATGAG ATCAAATGTC ATTTCCCAAA TTTCTTGTAG GCCGTTGTTT CAGATTCTTT 1099 CTGTCTTGGA ATGTAAACAT CTGATTCTGG AATGCAGAAG GAGGGGTCTG GGCATCTGTG 1159 GATTTTTGGC TACTAGAAGT GTCCCAGAAG TCACTGTATT TTTGAAACTT CTAACGTCAT 1219 AATTAAGTTT CTCTTGTCTT GGCATCAAGA ATAGTCAAGT TTTTTGGCCG GGCATGGTGG 1279 CTCATGCCTG TAATCCCAGC ACTTGGGGAG GCCAAGGCAG GCGGATCACA TGAGGCCAGG 1339 AATTCGAGAC CAACCTGGTC AGCATGGCAA AACCCCGTCT CTACTAAAAG TACAAAAATT 1399 AGCCAGGCGT GATGGCACGT GTCTGTAATC CCAGCTACTC TGGAGACTGA GGTGGGAGAA 1459 TCGCTTGAGA CTGGGAGGCA GAGGTTGCAG TGAACCGAGA TCATGCCACC GCACTTCAGC 1519 CTGGGTGACA GAGAAGGACT CCGTCTCAAA AAAAAAAGAA AAAAGAATAG TCATTTTTAA 1579 ACTACCTATC TCATGCAATG AAAGCATTTT CTTCCACAAA GAGCTTAATC CTCATGATAG 1639 GATTGCCTAG TGTCTCCCAT TTGCAGGTTT CTGGGTTGAT GTCTTAATGC ATAATACTGC 1699 AAGTGACATC AGCTGGCTGT GATGCTTCGA AATAGGTCTG CTCCTCACAG CTTTGGGAAT 1759 CTGAATGGAA GAAGAAAAGA GAGAAGTTAA CAACCTCCAC TGGGGCAACT TTGTGAACAT 1819 GTAGGCACTT AGTCATAGGA AACATATTAT GTGCAGGTCC TAGCCTGGGG TAGGAAAGTA 1879 GATAGACAGA AAATCATTAG GTAATTTAAG TACTAAATTG GGCAGGGCTT TTTAGTATCA 1939 AATCACTACT AGACCGTTTA ATTTGTTAAA TTATCTCTAG GATGGTGATT TATAACCTAC 1999 CCAAAGTTAT CGATATTCTT ACTAAACTCT GAGGCCTGAA GTTCTGTGAT AGACCTTAAA 2059 TAAGTGTCCT AAGTCAGTGG TTCCCAAATC TGGCTGGTCG GGAATACCTG GGAAGTTTGT 2119 TAAAATTTTT TAAAAATGTT TTAAGATTTT TGGGTCCTGA GCCAGGCGTG GTGGCTCACA 2179 CCTGTAATCC CAGCACTTTG GGAGGCTGAG GCAGGTGGAT CGCCTGAGGT CAGGAGTTCA 2239 AGATCAACCT GGCCAACATA CTGAAACCCC GTCTCTACTA AAAATAAGAA AAATTAGCTG 2299 GGCGTGGTGG CGGGCACCTG TAATCCCAGC TACTTGGGAG GCTGAGGCAG GAGAATCACT 2359 TGAACCTGGG AGTTAGAGGT TGCAGTGAGC TGAGATCACA CCATTGCGCT TCAGCCTGGG 2419 CAACAAGAGT GAAACTCCAT CTCC 2443SEQ ID NO: 3 Sequence length: 2443 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence characteristics: Characterizing symbol: CDS Location: 41. . 649 Method for Characterization: E Sequence: CCACACTTCC CGCCTCCCTA AAACGCACAC CCCGCTAGCC ATG GGC AGC CGC GAC 55 Met Gly Ser Arg Asp 15 CAC CTG TTC AAA GTG CTG GTG GTG GGG GAC GCC GCA GTG GGC AAG ACG 103 His Leu Phe Lys Val Val Val Gly Asp Ala Ala Val Gly Lys Thr 10 15 20 TCG CTG GTG CAG CGA TAT TCC CAG GAC AGC TTC AGC AAA CAC TAC AAG 151 Ser Leu Val Gln Arg Tyr Ser Gln Asp Ser Phe Ser Lys His Tyr Lys 25 30 35 TCC ACG GTG GGA GTG GAT TTT GCT CTG AAG GTT CTC CAG TGG TCT GAC 199 Ser Thr Val Gly Val Asp Phe Ala Leu Lys Val LeuGln Trp Ser Asp 40 45 50 TAC GAG ATA GTG CGG CTT CAG CTG TGG GAT ATT GCA GGG CAG GAG CGC 247 Tyr Glu Ile Val Arg Leu Gln Leu Trp Asp Ile Ala Gly Gln Glu Arg 55 60 65 TTC ACC TCT ATG ACA CGA TTG TAT TAT CGG GAT GCC TCT GCC TGT GTT 295 Phe Thr Ser Met Thr Arg Leu Tyr Tyr Arg Asp Ala Ser Ala Cys Val 70 75 80 85 ATT ATG TTT GAC GTT ACC AAT GCC ACT ACC TTC AGC AAC AGC CAG AGG 343 Ile Met Phe Asp Val Thr Asn Ala Thr Thr Phe Ser Asn Ser Gln Arg 90 95 100 TGG AA A CAG GAC CTA GAC AGC AAG CTC ACA CTA CCC AAT GGA GAG CCG 391 Trp Lys Gln Asp Leu Asp Ser Lys Leu Thr Leu Pro Asn Gly Glu Pro 105 110 115 GTG CCC TGC CTG CTC TTG GCC AAC AAG TGT GAT CTG TCC CCT TGG GCA 439 Val Pro Cys Leu Leu Leu Ala Asn Lys Cys Asp Leu Ser Pro Trp Ala 120 125 130 GTG AGC CGG GAC CAG ATT GAC CGG TTC AGT AAA GAG AAC GGT TTC ACA 487 Val Ser Arg Asp Gln Ile Asp Arg Phe Ser Lys Glu Asn Gly Phe Thr 135 140 145 GGT TGG ACA GAA ACA TCA GTC AAG GAG AAC AAA AAT ATT AAT GAG GCT 535 Gly Trp Thr Glu Thr Ser Val Lys Glu Asn Lys Asn Ile Asn Glu Ala 150 155 160 165 165 ATG AGA GTC CTC ATT GAA AAG ATG ATG AGA AAT TCC ACA GAA GAT ATC 583 Met Arg Val Leu Ile Glu Lys Met Met Arg Asn Ser Thr Glu Asp Ile 170 175 180 ATG TCT TTG TCC ACC CAA GGG GAC TAC ATC AAT CTA CAA ACC AAG TCC 631 Met Ser Leu Ser Thr Gln Gly Asp Tyr Ile Asn Leu Gln Thr Lys Ser 185 190 195 TCC AGC TGG TCC TGC TGC TAGTAGTGTT TGGCTTATTTTCCATCCCAG 679 Ser Ser Trp Ser Cys Cys 200 TTCTGGGAGG TCTTTTAAGT CTCTTCCCTT TGGTTGCCCA CCTGA CCATT TTATTAAGTA 739 CATTTGAATT GTCTCCTGAC TACTGTCCAG TAAGGAGGCC CATTGTCACT TAGAAAAGAC 799 ACCTGGAACC CATGTGCATT TCTGCATCTC CTGGATTAGC CTTTCACATG TTGCTGACTC 859 ACATTAGTGC CAGTTAGTGC CTTCGGTGTA AGATCTTCTC ATCAGCCCTC AATTTGTGAT 919 CCGGAATTTT GTGAGAAGGA TTAGAAATCA GCACCTGCGT TTTAGAGATC ATAATTCTCA 979 CCTACTTCTG AGCTTATTTT TCCATTTGAT ATTCATTGAT ATCATGACTT CCAATTGAGA 1039 GGAAAATGAG ATCAAATGTC ATTTCCCAAA TTTCTTGTAG GCCGTTGTTT CAGATTCTTT 1099 CTGTCTTGGA ATGTAAACAT CTGATTCTGG AATGCAGAAG GAGGGGTCTG GGCATCTGTG 1159 GATTTTTGGC TACTAGAAGT GTCCCAGAAG TCACTGTATT TTTGAAACTT CTAACGTCAT 1219 AATTAAGTTT CTCTTGTCTT GGCATCAAGA ATAGTCAAGT TTTTTGGCCG GGCATGGTGG 1279 CTCATGCCTG TAATCCCAGC ACTTGGGGAG GCCAAGGCAG GCGGATCACA TGAGGCCAGG 1339 AATTCGAGAC CAACCTGGTC AGCATGGCAA AACCCCGTCT CTACTAAAAG TACAAAAATT 1399 AGCCAGGCGT GATGGCACGT GTCTGTAATC CCAGCTACTC TGGAGACTGA GGTGGGAGAA 1459 TCGCTTGAGA CTGGGAGGCA GAGGTTGCAG TGAACCGAGA TCATGCCACC GCACTTCAGC 1519 CTGGGTGACA GAGAAGGACT CCGTCTCAAA AAAAAAAGAA AAAAGAATAG TCATT TTTAA 1579 ACTACCTATC TCATGCAATG AAAGCATTTT CTTCCACAAA GAGCTTAATC CTCATGATAG 1639 GATTGCCTAG TGTCTCCCAT TTGCAGGTTT CTGGGTTGAT GTCTTAATGC ATAATACTGC 1699 AAGTGACATC AGCTGGCTGT GATGCTTCGA AATAGGTCTG CTCCTCACAG CTTTGGGAAT 1759 CTGAATGGAA GAAGAAAAGA GAGAAGTTAA CAACCTCCAC TGGGGCAACT TTGTGAACAT 1819 GTAGGCACTT AGTCATAGGA AACATATTAT GTGCAGGTCC TAGCCTGGGG TAGGAAAGTA 1879 GATAGACAGA AAATCATTAG GTAATTTAAG TACTAAATTG GGCAGGGCTT TTTAGTATCA 1939 AATCACTACT AGACCGTTTA ATTTGTTAAA TTATCTCTAG GATGGTGATT TATAACCTAC 1999 CCAAAGTTAT CGATATTCTT ACTAAACTCT GAGGCCTGAA GTTCTGTGAT AGACCTTAAA 2059 TAAGTGTCCT AAGTCAGTGG TTCCCAAATC TGGCTGGTCG GGAATACCTG GGAAGTTTGT 2119 TAAAATTTTT TAAAAATGTT TTAAGATTTT TGGGTCCTGA GCCAGGCGTG GTGGCTCACA 2179 CCTGTAATCC CAGCACTTTG GGAGGCTGAG GCAGGTGGAT CGCCTGAGGT CAGGAGTTCA 2239 AGATCAACCT GGCCAACATA CTGAAACCCC GTCTCTACTA AAAATAAGAA AAATTAGCTG 2299 GGCGTGGTGG CGGGCACCTG TAATCCCAGC TACTTGGGAG GCTGAGGCAG GAGAATCACT 2359 TGAACCTGGG AGTTAGAGGT TGCAGTGAGC TGAGATCACA CCATTGCGCT TCAGCCTGGG 2419 CAACAAGAGT GAAACTCCAT CTCC 2443
【０１５６】配列番号：４ 配列の長さ：４４２ 配列の型：アミノ酸 トポロジー：直線状 配列の種類：蛋白 配列： Met Leu Pro Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln 1 5 10 15 Glu Arg Arg Phe Gln Leu Glu Gly Pro Glu Ser Leu Thr Val Gln Glu 20 25 30 Gly Leu Cys Val Leu Val Pro Cys Arg Leu Pro Thr Thr Leu Pro Ala 35 40 45 Ser Tyr Tyr Gly Tyr Gly Tyr Trp Phe Leu Glu Gly Ala Asp Val Pro 50 55 60 Val Ala Thr Asn Asp Pro Asp Glu Glu Val Gln Glu Glu Thr Arg Gly 65 70 75 80 Arg Phe His Leu Leu Trp Asp Pro Arg Arg Lys Asn Cys Ser Leu Ser 85 90 95 Ile Arg Asp Ala Arg Arg Arg Asp Asn Ala Ala Tyr Phe Phe Arg Leu 100 105 110 Lys Ser Lys Trp Met Lys Tyr Gly Tyr Thr Ser Ser Lys Leu Ser Val 115 120 125 Arg Val Met Ala Leu Thr His Arg Pro Asn Ile Ser Ile Pro Gly Thr 130 135 140 Leu Glu Ser Gly His Pro Ser Asn Leu Thr Cys Ser Val Pro Trp Val 145 150 155 160 Cys Glu Gln Gly Thr Pro Pro Ile Phe Ser Trp Met Ser Ala Ala Pro 165 170 175 Thr Ser Leu Gly Pro Arg Thr Thr Gln Ser Ser Val Leu Thr Ile Thr 180 185 190 Pro Arg Pro Gln Asp His Ser Thr Asn Leu Thr Cys Gln Val Thr Phe 195 200 205 Pro Gly Ala Gly Val Thr Met Glu Arg Thr Ile Gln Leu Asn Val Ser 210 215 220 Tyr Ala Pro Gln Lys Val Ala Ile Ser Ile Phe Gln Gly Asn Ser Ala 225 230 235 240 Ala Phe Lys Ile Leu Gln Asn Thr Ser Ser Leu Pro Val Leu Glu Gly 245 250 255 Gln Ala Leu Arg Leu Leu Cys Asp Ala Asp Gly Asn Pro Pro Ala His 260 265 270 Leu Ser Trp Phe Gln Gly Phe Pro Ala Leu Asn Ala Thr Pro Ile Ser 275 280 285 Asn Thr Gly Val Leu Glu Leu Pro Gln Val Gly Ser Ala Glu Glu Gly 290 295 300 Asp Phe Thr Cys Arg Ala Gln His Pro Leu Gly Ser Leu Gln Ile Ser 305 310 315 320 Leu Ser Leu Phe Val His Trp Lys Pro Glu Gly Arg Ala Gly Gly Val 325 330 335 Leu Gly Ala Val Trp Gly Ala Ser Ile Thr Thr Leu Val Phe Leu Cys 340 345 350 Val Cys Phe Ile Phe Arg Val Lys Thr Arg Arg Lys Lys Ala Ala Gln 355 360 365 Pro Val Gln Asn Thr Asp Asp Val Asn Pro Val Met Val Ser Gly Ser 370 375 380 Arg Gly His Gln His Gln Phe Gln Thr Gly Ile Val Ser Asp His Pro 385 390 395 400 Ala Glu Ala Gly Pro Ile Ser Glu Asp Glu Gln Glu Leu His Tyr Ala 405 410 415 Val Leu His Phe His Lys Val Gln Pro Gln Glu Pro Lys Val Thr Asp 420 425 430 Thr Glu Tyr Ser Glu Ile Lys Ile His Lys 435 440 SEQ ID NO: 4 Sequence length: 442 Sequence type: amino acid Topology: linear Sequence type: protein Sequence: Met Leu Pro Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln 1 5 10 15 Glu Arg Arg Phe Gln Leu Glu Gly Pro Glu Ser Leu Thr Val Gln Glu 20 25 30 Gly Leu Cys Val Leu Val Pro Cys Arg Leu Pro Thr Thr Leu Pro Ala 35 40 45 Ser Tyr Tyr Gly Tyr Gly Tyr Trp Phe Leu Glu Gly Ala Asp Val Pro 50 55 60 Val Ala Thr Asn Asp Pro Asp Glu Glu Val Gln Glu Glu Thr Arg Gly 65 70 75 80 Arg Phe His Leu Leu Trp Asp Pro Arg Arg Lys Asn Cys Ser Leu Ser 85 90 95 Ile Arg Asp Ala Arg Arg Arg Asp Asn Ala Ala Tyr Phe Phe Arg Leu 100 105 110 Lys Ser Lys Trp Met Lys Tyr Gly Tyr Thr Ser Ser Lys Leu Ser Val 115 120 125 Arg Val Met Ala Leu Thr His Arg Pro Asn Ile Ser Ile Pro Gly Thr 130 135 140 Leu Glu Ser Gly His Pro Ser Asn Leu Thr Cys Ser Val Pro Trp Val 145 150 155 160 Cys Glu Gln Gly Thr Pro Pro Ile Phe Ser Trp Met Ser Ala Ala Pro 165 170 175 Thr Ser Leu Gly Pr o Arg Thr Thr Gln Ser Ser Val Leu Thr Ile Thr 180 185 190 Pro Arg Pro Gln Asp His Ser Thr Asn Leu Thr Cys Gln Val Thr Phe 195 200 205 Pro Gly Ala Gly Val Thr Met Glu Arg Thr Ile Gln Leu Asn Val Ser 210 215 220 Tyr Ala Pro Gln Lys Val Ala Ile Ser Ile Phe Gln Gly Asn Ser Ala 225 230 235 240 Ala Phe Lys Ile Leu Gln Asn Thr Ser Ser Leu Pro Val Leu Glu Gly 245 250 255 Gln Ala Leu Arg Leu Leu Cys Asp Ala Asp Gly Asn Pro Pro Ala His 260 265 270 Leu Ser Trp Phe Gln Gly Phe Pro Ala Leu Asn Ala Thr Pro Ile Ser 275 280 285 Asn Thr Gly Val Leu Glu Leu Pro Gln Val Gly Ser Ala Glu Glu Gly 290 295 300 Asp Phe Thr Cys Arg Ala Gln His Pro Leu Gly Ser Leu Gln Ile Ser 305 310 315 320 Leu Ser Leu Phe Val His Trp Lys Pro Glu Gly Arg Ala Gly Gly Val 325 330 335 Leu Gly Ala Val Trp Gly Ala Ser Ile Thr Thr Lele Val Phe Leu Cys 340 345 350 Val Cys Phe Ile Phe Arg Val Lys Thr Arg Arg Lys Lys Ala Ala Gln 355 360 365 Pro Val Gln Asn Thr Asp Asp Val Asn Pro Val Met Val Ser Gly Ser 370 375 380 Arg Gly His Gln His G ln Phe Gln Thr Gly Ile Val Ser Asp His Pro 385 390 395 400 Ala Glu Ala Gly Pro Ile Ser Glu Asp Glu Gln Glu Leu His Tyr Ala 405 410 415 Val Leu His Phe His Lys Val Gln Pro Gln Glu Pro Lys Val Thr Asp 420 425 430 Thr Glu Tyr Ser Glu Ile Lys Ile His Lys 435 440
【０１５７】配列番号：５ 配列の長さ：１３２６ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列： ＡＴＧＣＴＡＣＣＧＣ ＴＧＣＴＧＣＴＧＣＣ ＣＣＴＧＣＴＧＴＧＧ ＧＣＡ
ＧＧＧＧＣＣＣ ＴＧＧＣＴＣＡＧＧＡ ＧＣＧＧＡＧＡＴＴＣ ６０ ＣＡＧＣＴＧＧＡＧＧ ＧＧＣＣＡＧＡＧＴＣ ＡＣＴＧＡＣＧＧＴＧ ＣＡＧ
ＧＡＧＧＧＴＣ ＴＧＴＧＣＧＴＣＣＴ ＣＧＴＡＣＣＣＴＧＣ １２０ ＡＧＡＴＴＧＣＣＣＡ ＣＴＡＣＣＣＴＴＣＣ ＡＧＣＣＴＣＧＴＡＣ ＴＡＴ
ＧＧＴＴＡＴＧ ＧＣＴＡＣＴＧＧＴＴ ＣＣＴＧＧＡＡＧＧＧ １８０ ＧＣＴＧＡＴＧＴＴＣ ＣＡＧＴＧＧＣＣＡＣ ＡＡＡＣＧＡＣＣＣＡ ＧＡＣ
ＧＡＡＧＡＡＧ ＴＧＣＡＧＧＡＧＧＡ ＧＡＣＣＣＧＧＧＧＣ ２４０ ＣＧＡＴＴＣＣＡＣＣ ＴＣＣＴＣＴＧＧＧＡ ＴＣＣＣＡＧＡＡＧＧ ＡＡＧ
ＡＡＣＴＧＣＴ ＣＣＣＴＧＡＧＣＡＴ ＣＡＧＡＧＡＴＧＣＣ ３００ ＣＧＧＡＧＧＡＧＧＧ ＡＣＡＡＴＧＣＴＧＣ ＡＴＡＣＴＴＣＴＴＴ ＣＧＧ
ＴＴＧＡＡＧＴ ＣＣＡＡＡＴＧＧＡＴ ＧＡＡＡＴＡＣＧＧＴ ３６０ ＴＡＴＡＣＡＴＣＴＴ ＣＣＡＡＧＣＴＣＴＣ ＴＧＴＧＣＧＴＧＴＧ ＡＴＧ
ＧＣＣＣＴＧＡ ＣＣＣＡＣＡＧＧＣＣ ＣＡＡＣＡＴＣＴＣＣ ４２０ ＡＴＣＣＣＡＧＧＧＡ ＣＣＣＴＧＧＡＧＴＣ ＴＧＧＣＣＡＴＣＣＣ ＡＧＣ
ＡＡＴＣＴＧＡ ＣＣＴＧＣＴＣＴＧＴ ＧＣＣＣＴＧＧＧＴＣ ４８０ ＴＧＴＧＡＧＣＡＧＧ ＧＧＡＣＧＣＣＣＣＣ ＣＡＴＣＴＴＣＴＣＣ ＴＧＧ
ＡＴＧＴＣＡＧ ＣＴＧＣＣＣＣＣＡＣ ＣＴＣＣＣＴＧＧＧＣ ５４０ ＣＣＣＡＧＧＡＣＣＡ ＣＣＣＡＧＴＣＣＴＣ ＧＧＴＧＣＴＣＡＣＡ ＡＴＣ
ＡＣＣＣＣＡＣ ＧＧＣＣＣＣＡＧＧＡ ＣＣＡＣＡＧＣＡＣＣ ６００ ＡＡＣＣＴＣＡＣＣＴ ＧＴＣＡＧＧＴＧＡＣ ＧＴＴＣＣＣＴＧＧＡ ＧＣＣ
ＧＧＴＧＴＧＡ ＣＣＡＴＧＧＡＧＡＧ ＡＡＣＣＡＴＣＣＡＧ ６６０ ＣＴＣＡＡＴＧＴＣＴ ＣＣＴＡＴＧＣＴＣＣ ＡＣＡＧＡＡＡＧＴＧ ＧＣＣ
ＡＴＣＡＧＣＡ ＴＣＴＴＣＣＡＡＧＧ ＡＡＡＣＡＧＣＧＣＡ ７２０ ＧＣＣＴＴＣＡＡＡＡ ＴＣＣＴＧＣＡＡＡＡ ＣＡＣＣＴＣＧＴＣＣ ＣＴＣ
ＣＣＴＧＴＣＣ ＴＧＧＡＧＧＧＣＣＡ ＧＧＣＴＣＴＧＣＧＧ ７８０ ＣＴＧＣＴＣＴＧＴＧ ＡＴＧＣＴＧＡＣＧＧ ＣＡＡＣＣＣＣＣＣＴ ＧＣＡ
ＣＡＣＣＴＧＡ ＧＣＴＧＧＴＴＣＣＡ ＧＧＧＣＴＴＣＣＣＣ ８４０ ＧＣＣＣＴＧＡＡＣＧ ＣＣＡＣＣＣＣＣＡＴ ＣＴＣＣＡＡＴＡＣＣ ＧＧＧ
ＧＴＣＣＴＧＧ ＡＧＣＴＧＣＣＴＣＡ ＡＧＴＡＧＧＧＴＣＴ ９００ ＧＣＡＧＡＡＧＡＡＧ ＧＡＧＡＴＴＴＣＡＣ ＣＴＧＣＣＧＴＧＣＴ ＣＡＧ
ＣＡＴＣＣＴＣ ＴＧＧＧＣＴＣＣＣＴ ＧＣＡＡＡＴＣＴＣＴ ９６０ ＣＴＧＡＧＴＣＴＣＴ ＴＴＧＴＧＣＡＴＴＧ ＧＡＡＡＣＣＡＧＡＡ ＧＧＣ
ＡＧＧＧＣＴＧ ＧＴＧＧＴＧＴＣＣＴ ＧＧＧＡＧＣＡＧＴＣ １０２０ ＴＧＧＧＧＡＧＣＴＡ ＧＣＡＴＣＡＣＡＡＣ ＣＣＴＧＧＴＴＴＴＣ ＣＴＣ
ＴＧＴＧＴＴＴ ＧＣＴＴＣＡＴＣＴＴ ＣＡＧＡＧＴＧＡＡＧ １０８０ ＡＣＴＡＧＡＡＧＧＡ ＡＧＡＡＡＧＣＡＧＣ ＣＣＡＧＣＣＡＧＴＧ ＣＡＡ
ＡＡＣＡＣＧＧ ＡＴＧＡＴＧＴＧＡＡ ＣＣＣＣＧＴＣＡＴＧ １１４０ ＧＴＣＴＣＡＧＧＣＴ ＣＣＡＧＧＧＧＴＣＡ ＴＣＡＧＣＡＣＣＡＧ ＴＴＣ
ＣＡＧＡＣＡＧ ＧＣＡＴＡＧＴＴＴＣ ＡＧＡＣＣＡＣＣＣＴ １２００ ＧＣＴＧＡＧＧＣＴＧ ＧＣＣＣＣＡＴＣＴＣ ＡＧＡＡＧＡＴＧＡＧ ＣＡＧ
ＧＡＧＣＴＣＣ ＡＣＴＡＣＧＣＴＧＴ ＣＣＴＡＣＡＣＴＴＣ １２６０ ＣＡＣＡＡＧＧＴＧＣ ＡＡＣＣＴＣＡＧＧＡ ＡＣＣＡＡＡＧＧＴＣ ＡＣＣ
ＧＡＣＡＣＴＧ ＡＧＴＡＣＴＣＡＧＡ ＡＡＴＣＡＡＧＡＴＡ １３２０ ＣＡＣＡＡＧ
１３２６SEQ ID NO: 5 Sequence length: 1326 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence: ATGCTACGCGCTGCTGCTGCCCCTGCTGTGG GCA
GGGGCCC TGGCTCAGGA GCGGAGATCTC 60 CAGCTGGAGG GGCCAGAGTC ACTGACGGGTG CAG
GAGGGGTC TGTGCGTCCT CGTACCCTGC 120 AGATTGCCCA CTACCCTTCC AGCCTCGCTAC TAT
GGTTATG GCTACTGGTT CCTGGAAGGG 180 GCTGATGTTC CAGTGGCCAC AAACGACCCA GAC
GAAGAAG TGCAGGAGGA GACCCGGGGC 240 CGATTCCACC TCCTCTGGGA TCCCAGAAGG AAG
AACTGCT CCCTGAGCAT CAGAGATGCC 300 CGGAGGAGGGG ACAATGCTGC ATACTTCTTTT CGG
TTGAAGT CCAAATGGAT GAAATACGGT 360 TATACATCTT CCAAGCTCTC TGTGCGTGTGTG ATG
GCCCTGA CCCACAGGCC CAACATCTCC 420 ATCCCAGGGA CCCTGGAGTC TGGCCATCCC AGC
AATCTGA CCTGCTCTGT GCCCTGGGTC 480 TGTGAGCAGGG GGACGCCCCC CATCTTCTCC TGG
AGTTCAG CTGCCCCCAC CTCCCTGGGC 540 CCCAGGACCA CCCATCCCTC GGTGCTCACA ATC
ACCCCAC GGCCCCAGGA CCACAGCACC 600 AACCTCACCT GTCAGGTGAC GTTCCCTGGA GCC
GGTGTGA CCATGGAGAG AACCATCCAG 660 CTCAATGTCT CCTATGCTCC ACAGAAAGTTG GCC
ATCAGCA TCTTCCAAGG AAACACGCGCA 720 GCCTTCAAAA TCCTGCAAAA CACCTCGTCC CTC
CCTGTCC TGGAGGGCCA GGCTCTGCGG 780 CTGCTCTGTG ATGCTGACGG CAACCCCCCCT GCA
CACCTGA GCTGGTTCCA GGGCTTCCCC 840 GCCCTCGAACG CCACCCCCAT CTCCAATCACC GGG
GTCCTGG AGCTGCCTCA AGTAGGGTCT 900 GCAGAAGAAG GAGATTTCAC CTGCCGTGCT CAG
CATCCTC TGGGCTCCCT GCAATCTCT 960 CTGAGTCTCT TTGTGCATTG GAAACCAGAA GGC
AGGGCTG GTGGTGTCCT GGGAGCAGTC 1020 TGGGGAGCTA GCATCACAAC CCTGGTTTTC CTC
TGTGTTT GCTTCATCTT CAGAGTGAAG 1080 ACTAGAAGGA AGAAAGCAGCCCAGCCAGTG CAA
AACACGG ATGATGTGAA CCCCGTCATG 1140 GTTCCAGGCT CCAGGGGTCA TCAGCACCAG TTC
CAGACAG GCATAGTTTC AGACCACCCT 1200 GCTGAGGCTGGCCCCATCTC AGAAGATGAG CAG
GAGCTCC ACTACGCTTGT CCTACACTTC 1260 CACAAGGTGC AACCTCAGGA ACCAAAGGTC ACC
GACACTG AGTACTCGA AATCAAGATA 1320 CACAAG
1326
【０１５８】配列番号：６ 配列の長さ：２８０９ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：ＤＮＡ （ｃＤＮＡ） 配列の特徴： 特徴を表わす記号：CDS 存在位置：２３７．．１５６２ 特徴を決定した方法：Ｅ 配列： GCGGGACACA GTCTCTTCTC CTCTGCTCTT CTTTGGGCAG AGGGTCTCAA AGTTTCCGTC 60 TGCTCTGTGC AGAGGGAGTG GAGCTCCGAG GGCTTGTGGC TTCGCAGTTC CTCTTCTGTG 120 AACAGCCGAG ATCACGCGCT CCTCCCCAGC CACCCGTTCC TCCCCGCAGT CCTTCCCCTC 180 CACTCCCTTC CCCTTCTCTG CTCATGCAGG GAGCCCAGAA AGCCTCCGCC TCAGAG 236 ATG CTA CCG CTG CTG CTG CCC CTG CTG TGG GCA GGG GCC CTG GCT CAG 284 Met Leu Pro Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln 1 5 10 15 GAG CGG AGA TTC CAG CTG GAG GGG CCA GAG TCA CTG ACG GTG CAG GAG 332 Glu Arg Arg Phe Gln Leu Glu Gly Pro Glu Ser Leu Thr Val Gln Glu 20 25 30 GGT CTG TGC GTC CTC GTA CCC TGC AGA TTG CCC ACT ACC CTT CCA GCC 380 Gly Leu Cys Val Leu Val Pro Cys Arg Leu Pro Thr Thr Leu Pro Ala 35 40 45 TCG TAC TAT GGT TAT GGC TAC TGG TTC CTG GAA GGG GCT GAT GTT CCA 428 Ser Tyr Tyr Gly Tyr Gly Tyr Trp Phe Leu Glu Gly Ala Asp Val Pro 50 55 60 GTG GCC ACA AAC GAC CCA GAC GAA GAA GTG CAG GAG GAG ACC CGG GGC 476 Val Ala Thr Asn Asp Pro Asp Glu Glu Val Gln Glu Glu Thr Arg Gly 65 70 75 80 CGA TTC CAC CTC CTC TGG GAT CCC AGA AGG AAG AAC TGC TCC CTG AGC 524 Arg Phe His Leu Leu Trp Asp Pro Arg Arg Lys Asn Cys Ser Leu Ser 85 90 95 ATC AGA GAT GCC CGG AGG AGG GAC AAT GCT GCA TAC TTC TTT CGG TTG 572 Ile Arg Asp Ala Arg Arg Arg Asp Asn Ala Ala Tyr Phe Phe Arg Leu 100 105 110 AAG TCC AAA TGG ATG AAA TAC GGT TAT ACA TCT TCC AAG CTC TCT GTG 620 Lys Ser Lys Trp Met Lys Tyr Gly Tyr Thr Ser Ser Lys Leu Ser Val 115 120 125 CGT GTG ATG GCC CTG ACC CAC AGG CCC AAC ATC TCC ATC CCA GGG ACC 668 Arg Val Met Ala Leu Thr His Arg Pro Asn Ile Ser Ile Pro Gly Thr 130 135 140 CTG GAG TCT GGC CAT CCC AGC AAT CTG ACC TGC TCT GTG CCC TGG GTC 716 Leu Glu Ser Gly His Pro Ser Asn Leu Thr Cys Ser Val Pro Trp Val 145 150 155 160 TGT GAG CAG GGG ACG CCC CCC ATC TTC TCC TGG ATG TCA GCT GCC CCC 764 Cys Glu Gln Gly Thr Pro Pro Ile Phe Ser Trp Met Ser Ala Ala Pro 165 170 175 ACC TCC CTG GGC CCC AGG ACC ACC CAG TCC TCG GTG CTC ACA ATC ACC 812 Thr Ser Leu Gly Pro Arg Thr Thr Gln Ser Ser Val Leu Thr Ile Thr 180 185 190 CCA CGG CCC CAG GAC CAC AGC ACC AAC CTC ACC TGT CAG GTG ACG TTC 860 Pro Arg Pro Gln Asp His Ser Thr Asn Leu Thr Cys Gln Val Thr Phe 195 200 205 CCT GGA GCC GGT GTG ACC ATG GAG AGA ACC ATC CAG CTC AAT GTC TCC 908 Pro Gly Ala Gly Val Thr Met Glu Arg Thr Ile Gln Leu Asn Val Ser 210 215 220 TAT GCT CCA CAG AAA GTG GCC ATC AGC ATC TTC CAA GGA AAC AGC GCA 956 Tyr Ala Pro Gln Lys Val Ala Ile Ser Ile Phe Gln Gly Asn Ser Ala 225 230 235 240 GCC TTC AAA ATC CTG CAA AAC ACC TCG TCC CTC CCT GTC CTG GAG GGC 1004 Ala Phe Lys Ile Leu Gln Asn Thr Ser Ser Leu Pro Val Leu Glu Gly 245 250 255 CAG GCT CTG CGG CTG CTC TGT GAT GCT GAC GGC AAC CCC CCT GCA CAC 1052 Gln Ala Leu Arg Leu Leu Cys Asp Ala Asp Gly Asn Pro Pro Ala His 260 265 270 CTG AGC TGG TTC CAG GGC TTC CCC GCC CTG AAC GCC ACC CCC ATC TCC 1100 Leu Ser Trp Phe Gln Gly Phe Pro Ala Leu Asn Ala Thr Pro Ile Ser 275 280 285 AAT ACC GGG GTC CTG GAG CTG CCT CAA GTA GGG TCT GCA GAA GAA GGA 1148 Asn Thr Gly Val Leu Glu Leu Pro Gln Val Gly Ser Ala Glu Glu Gly 290 295 300 GAT TTC ACC TGC CGT GCT CAG CAT CCT CTG GGC TCC CTG CAA ATC TCT 1196 Asp Phe Thr Cys Arg Ala Gln His Pro Leu Gly Ser Leu Gln Ile Ser 305 310 315 320 CTG AGT CTC TTT GTG CAT TGG AAA CCA GAA GGC AGG GCT GGT GGT GTC 1244 Leu Ser Leu Phe Val His Trp Lys Pro Glu Gly Arg Ala Gly Gly Val 325 330 335 CTG GGA GCA GTC TGG GGA GCT AGC ATC ACA ACC CTG GTT TTC CTC TGT 1292 Leu Gly Ala Val Trp Gly Ala Ser Ile Thr Thr Leu Val Phe Leu Cys 340 345 350 GTT TGC TTC ATC TTC AGA GTG AAG ACT AGA AGG AAG AAA GCA GCC CAG 1340 Val Cys Phe Ile Phe Arg Val Lys Thr Arg Arg Lys Lys Ala Ala Gln 355 360 365 CCA GTG CAA AAC ACG GAT GAT GTG AAC CCC GTC ATG GTC TCA GGC TCC 1388 Pro Val Gln Asn Thr Asp Asp Val Asn Pro Val Met Val Ser Gly Ser 370 375 380 AGG GGT CAT CAG CAC CAG TTC CAG ACA GGC ATA GTT TCA GAC CAC CCT 1436 Arg Gly His Gln His Gln Phe Gln Thr Gly Ile Val Ser Asp His Pro 385 390 395 400 GCT GAG GCT GGC CCC ATC TCA GAA GAT GAG CAG GAG CTC CAC TAC GCT 1484 Ala Glu Ala Gly Pro Ile Ser Glu Asp Glu Gln Glu Leu His Tyr Ala 405 410 415 GTC CTA CAC TTC CAC AAG GTG CAA CCT CAG GAA CCA AAG GTC ACC GAC 1532 Val Leu His Phe His Lys Val Gln Pro Gln Glu Pro Lys Val Thr Asp 420 425 430 ACT GAG TAC TCA GAA ATC AAG ATA CAC AAG TGAGGAATTG TCCAAAGCCA 1582 Thr Glu Tyr Ser Glu Ile Lys Ile His Lys 435 440 TAACCTTGAT TGGAGAGAAC ATGGTACCTC TCAGTGTATT GGTTACTAGG GCTGCCACAG 1642 CAATGTACCA CAAACCGAGT GACATAAACA CAGAACTTTA TTTTCGTATA GTTTCAGATG 1702 TTAGAGGTCT GAGAACAAGG TGTTATCAGG GTTGGTCCCT TCTAAGGCCT CTCTTGTTGG 1762 CTTGTAGATG GCTGTCTCCT CCTTGTGTCT TCACATGGTC TTTCCTCTGA GTGTGTTTGT 1822 GTCCTAATCT TCTCTTCTTA TAAAGACACT AGTCATATTG GATTAGGGCC TCCCCATGAC 1882 CTAATTTAAA TAAATTAACT ATTTAAAGAC CCTCCAAATA CAGTAACCTT CTGGATATTA 1942 GATTTAGGAC TTCCAACATA TAATTTTAGA AGGGAACAAT TTAGCCCATA ACACTGTGTC 2002 CAATTCTTTT AAAATTAATG TTTTTGTTGT AAATGGACTA TATAAATACC TTCGTATATA 2062 TGGCAGACCG CAGACTTCTG TCCAAGAGAA CTGAGTTCAA CTCCATCTAT GCCAGCCTGG 2122 GCAACAGAGC GAGACTCCAA CTCAGAAAAA GCAAAACAAA ACAAACAAAC AAGCAAAAAA 2182 CCACAATTAG ACTGACAGCT GACTTTTTTA GGAGCAATAT TGGAAGGCTA AATGCAATAG 2242 AAAGATGTCT TTGATGCCTT AAGAGAAATA AATGTTGTTT TAGAAAGCCT ACTCAATGAA 2302 AACACATTTT AAGACTGAAA GTGAAATATA GATATTTTAA GGAAAACCAA AATATGTGAG 2362 TGTTAATAAA GAAAAGATTT CTCAAATAAA TTCTAAAACA TATAATTCAG GTATTAGGAA 2422 AGTGATCCCA GATTAGATTT TTGAGATCCA AAAAAAATGC AAAACCTAGG AAAGTAGCAA 2482 ATATGTGAGC AAAATGAAAC AAATACTTGT TGTAAAAATG ATGGTTTGTA GAGGGGTCAA 2542 ACATCAAATG TAATATTGAA ATACCAATAT TATATAGCCC AGAAACTATA ATAACATAAA 2602 GTTCAGAAGA GTGTAAATAG AATTTATATT ACCATAAAGT CCTTTATATT TTTCCAGAGA 2662 AAATTAAATG TTATGATGAA TGTTACATTT GGATAATTTA TTATTGTAAT CTCGAGGAAA 2722 TTTACTTAAA GAATCGAAGC CAAGTTTACC ACCTGTGAAC TAGAGGAAGT ATAAAAGGTG 2782 ATAGAAACAT TATTCAGTCA AACCAGA 2809SEQ ID NO: 6 Sequence length: 2809 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence characteristics: Characterizing symbol: CDS Location: 237. . 1562 method to determine the characteristics: E SEQ: GCGGGACACA GTCTCTTCTC CTCTGCTCTT CTTTGGGCAG AGGGTCTCAA AGTTTCCGTC 60 TGCTCTGTGC AGAGGGAGTG GAGCTCCGAG GGCTTGTGGC TTCGCAGTTC CTCTTCTGTG 120 AACAGCCGAG ATCACGCGCT CCTCCCCAGC CACCCGTTCC TCCCCGCAGT CCTTCCCCTC 180 CACTCCCTTC CCCTTCTCTG CTCATGCAGG GAGCCCAGAA AGCCTCCGCC TCAGAG 236 ATG CTA CCG CTG CTG CTG CCC CTG CTG TGG GCA GGG GCC CTG GCT CAG 284 Met Leu Pro Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln 1 5 10 15 GAG CGG AGA TTC CAG CTG GAG GGG CCA GAG TCA CTG ACG GTG CAG GAG 332 Glu Arg Arg Phe Gln Leu Glu Gly Pro Glu Ser Leu Thr Val Gln Glu 20 25 30 GGT CTG TGC GTC CTC GTA CCC TGC AGA TTG CCC ACT ACC CTT CCA GCC 380 Gly Leu Cys Val Leu Val Pro Cys Arg Leu Pro Thr Thr Leu Pro Ala 35 40 45 TCG TAC TAT GGT TAT GGC TAC TGG TTC CTG GAA GGG GCT GAT GTT CCA 428 Ser Tyr Tyr Gly Tyr Gly Tyr Trp Phe Leu Glu Gly Ala Asp Val Pro 50 55 60 GTG GCC ACA AAC GAC CCA GAC GAA GAA GTG CAG GAG GAG ACC CGG GGC 476 Val Ala Thr Asn Asp Pro Asp Glu Glu Val Gln Glu Glu Thr Arg Gly 65 70 75 80 CGA TTC CAC CTC CTC TGG GAT CCC AGA AGG AAG AAC TGC TCC CTG AGC 524 Arg Phe His Leu Leu Trp Asp Pro Arg Arg Lys Asn Cys Ser Leu Ser 85 90 95 ATC AGA GAT GCC CGG AGG AGG GAC AAT GCT GCA TAC TTC TTT CGG TTG 572 Ile Arg Asp Ala Arg Arg Arg Asp Asn Ala Ala Tyr Phe Phe Arg Leu 100 105 110 AAG TCC AAA TGG ATG AAA TAC GGT TAT ACA TCT TCC AAG CTC TCT GTG 620 Lys Ser Lys Trp Met Lys Tyr Gly Tyr Thr Ser Ser Lys Leu Ser Val 115 120 125 CGT GTG ATG GCC CTG ACC CAC AGG CCC AAC ATC TCC ATC CCA GGG ACC 668 Arg Val Met Ala Leu Thr His Arg Pro Asn Ile Ser Ile Pro Gly Thr 130 135 140 CTG GAG TCT GGC CAT CCC AGC AAT CTG ACC TGC TCT GTG CCC TGG GTC 716 Leu Glu Ser Gly His Pro Ser Asn Leu Thr Cys Ser Val Pro Trp Val 145 150 155 160 TGT GAG CAG GGG ACG CCC CCC ATC TTC TCC TGG ATG TCA GCT GCC CCC 764 Cys Glu Gln Gly Thr Pro Pro Ile Phe Ser Trp Met Ser Ala Ala Pro 165 170 175 ACC TCC CTG GGC CCC AGG ACC ACC CAG TCC TCG GTG CTC ACA ATC ACC 812 Thr Ser Leu Gly Pro Arg T hr Thr Gln Ser Ser Val Leu Thr Ile Thr 180 185 190 CCA CGG CCC CAG GAC CAC AGC ACC AAC CTC ACC TGT CAG GTG ACG TTC 860 Pro Arg Pro Gln Asp His Ser Thr Asn Leu Thr Cys Gln Val Thr Phe 195 200 205 CCT GGA GCC GGT GTG ACC ATG GAG AGA ACC ATC CAG CTC AAT GTC TCC 908 Pro Gly Ala Gly Val Thr Met Glu Arg Thr Ile Gln Leu Asn Val Ser 210 215 220 TAT GCT CCA CAG AAA GTG GCC ATC AGC ATC TTC CAA GGA AAC AGC GCA 956 Tyr Ala Pro Gln Lys Val Ala Ile Ser Ile Phe Gln Gly Asn Ser Ala 225 230 235 240 GCC TTC AAA ATC CTG CAA AAC ACC TCG TCC CTC CCT GTC CTG GAG GGC 1004 Ala Phe Lys Ile Leu Gln Asn Thr Ser Ser Leu Pro Val Leu Glu Gly 245 250 255 CAG GCT CTG CGG CTG CTC TGT GAT GCT GAC GGC AAC CCC CCT GCA CAC 1052 Gln Ala Leu Arg Leu Leu Cys Asp Ala Asp Gly Asn Pro Pro Ala His 260 265 270 CTG AGC TGG TTC CAG GGC TTC CCC GCC CTG AAC GCC ACC CCC ATC TCC 1100 Leu Ser Trp Phe Gln Gly Phe Pro Ala Leu Asn Ala Thr Pro Ile Ser 275 280 285 AAT ACC GGG GTC CTG GAG CTG CCT CAA GTA GGG TCT GCA GAA GAA GGA 1148 Asn Thr G ly Val Leu Glu Leu Pro Gln Val Gly Ser Ala Glu Glu Gly 290 295 300 GAT TTC ACC TGC CGT GCT CAG CAT CCT CTG GGC TCC CTG CAA ATC TCT 1196 Asp Phe Thr Cys Arg Ala Gln His Pro Leu Gly Ser Leu Gln Ile Ser 305 310 315 320 CTG AGT CTC TTT GTG CAT TGG AAA CCA GAA GGC AGG GCT GGT GGT GTC 1244 Leu Ser Leu Phe Val His Trp Lys Pro Glu Gly Arg Ala Gly Gly Val 325 330 335 CTG GGA GCA GTC TGG GGA GCT AGC ATC ACA ACC CTG GTT TTC CTC TGT 1292 Leu Gly Ala Val Trp Gly Ala Ser Ile Thr Thr Leu Val Phe Leu Cys 340 345 350 GTT TGC TTC ATC TTC AGA GTG AAG ACT AGA AGG AAG AAA GCA GCC CAG 1340 Val Cys Phe Ile Phe Arg Val Lys Thr Arg Arg Lys Lys Ala Ala Gln 355 360 365 CCA GTG CAA AAC ACG GAT GAT GTG AAC CCC GTC ATG GTC TCA GGC TCC 1388 Pro Val Gln Asn Thr Asp Asp Val Asn Pro Val Met Val Ser Gly Ser 370 375 380 380 AGG GGT CAT CAG CAC CAG TTC CAG ACA GGC ATA GTT TCA GAC CAC CCT 1436 Arg Gly His Gln His Gln Phe Gln Thr Gly Ile Val Ser Asp His Pro 385 390 395 400 GCT GAG GCT GGC CCC ATC TCA GAA GAT GAG CAG GAG CTC CAC TAC GCT 1484 Ala Glu Ala Gly Pro Ile Ser Glu Asp Glu Gln Glu Leu His Tyr Ala 405 410 415 GTC CTA CAC TTC CAC AAG GTG CAA CCT CAG GAA CCA AAG GTC ACC GAC 1532 Val Leu His Phe His Lys Val Gln Pro Gln Glu Pro Lys Val Thr Asp 420 425 430 ACT GAG TAC TCA GAA ATC AAG ATA CAC AAG TGAGGAATTG TCCAAAGCCA 1582 Thr Glu Tyr Ser Glu Ile Lys Ile His Lys 435 440 TAACCTTGAT TGGATTGAGAAC ATGGTACCTC TCAGTGTATT GGTTACGAGTACGATCCATCGAGTCAGTCAGTGAGCATGAC GTTGGTCCCT TCTAAGGCCT CTCTTGTTGG 1762 CTTGTAGATG GCTGTCTCCT CCTTGTGTCT TCACATGGTC TTTCCTCTGA GTGTGTTTGT 1822 GTCCTAATCT TCTCTTCTTA TAAAGACACT AGTCATATTG GATTAGGGCC TCCCCATGAC 1882 CTAATTTAAA TAAATTAACT ATTTAAAGAC CCTCCAAATA CAGTAACCTT CTGGATATTA 1942 GATTTAGGAC TTCCAACATA TAATTTTAGA AGGGAACAAT TTAGCCCATA ACACTGTGTC 2002 CAATTCTTTT AAAATTAATG TTTTTGTTGT AAATGGACTA TATAAATACC TTCGTATATA 2062 TGGCAGACCG CAGACTTCTG TCCAAGAGAA CTGAGTTCAA CTCCATCTAT GCCAGCCTGG 2122 GCAACAGAGC GAGACTCCAA CTCAGAAAAA GCAAAACAAA ACAAACAAAC AAGCAAAAAA 2182 CCACAATTAG ACTGACAGCT GACTTTTTTA GGAGCAATAT TGGAAGGCTA AATGCAATAG 2242 AAAGATGTCT TTGATGCCTT AAGAGAAATA AATGTTGTTT TAGAAAGCCT ACTCAATGAA 2302 AACACATTTT AAGACTGAAA GTGAAATATA GATATTTTAA GGAAAACCAA AATATGTGAG 2362 TGTTAATAAA GAAAAGATTT CTCAAATAAA TTCTAAAACA TATAATTCAG GTATTAGGAA 2422 AGTGATCCCA GATTAGATTT TTGAGATCCA AAAAAAATGC AAAACCTAGG AAAGTAGCAA 2482 ATATGTGAGC AAAATGAAAC AAATACTTGT TGTAAAAATG ATGGTTTGTA GAGGGGTCAA 2542 ACATCAAATG TAATATTGAA ATACCAATAT TATATAGCCC AGAAACTATA ATAACATAAA 2602 GTTCAGAAGA GTGTAAATAG AATTTATATT ACCATAAAGT CCTTTATATT TTTCCAGAGA 2662 AAATTAAATG TTATGATGAA TGTTACATTT GGATAATTTA TTATTGTAAT CTCGAGGAAA 2722 TTTACTTAAAGATCGATCACGATCACGATCACGATCAGGATCACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATACGAGATCAAGATACGAGATCAGAGATCAGATACGA
【０１５９】配列番号：７ 配列の長さ：３４２ 配列の型：アミノ酸 トポロジー：直線状 配列の種類：蛋白 配列： Met Leu Pro Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln 1 5 10 15 Glu Arg Arg Phe Gln Leu Glu Gly Pro Glu Ser Leu Thr Val Gln Glu 20 25 30 Gly Leu Cys Val Leu Val Pro Cys Arg Leu Pro Thr Thr Leu Pro Ala 35 40 45 Ser Tyr Tyr Gly Tyr Gly Tyr Trp Phe Leu Glu Gly Ala Asp Val Pro 50 55 60 Val Ala Thr Asn Asp Pro Asp Glu Glu Val Gln Glu Glu Thr Arg Gly 65 70 75 80 Arg Phe His Leu Leu Trp Asp Pro Arg Arg Lys Asn Cys Ser Leu Ser 85 90 95 Ile Arg Asp Ala Arg Arg Arg Asp Asn Ala Ala Tyr Phe Phe Arg Leu 100 105 110 Lys Ser Lys Trp Met Lys Tyr Gly Tyr Thr Ser Ser Lys Leu Ser Val 115 120 125 Arg Val Met Ala Leu Thr His Arg Pro Asn Ile Ser Ile Pro Gly Thr 130 135 140 Leu Glu Ser Gly His Pro Ser Asn Leu Thr Cys Ser Val Pro Trp Val 145 150 155 160 Cys Glu Gln Gly Thr Pro Pro Ile Phe Ser Trp Met Ser Ala Ala Pro 165 170 175 Thr Ser Leu Gly Pro Arg Thr Thr Gln Ser Ser Val Leu Thr Ile Thr 180 185 190 Pro Arg Pro Gln Asp His Ser Thr Asn Leu Thr Cys Gln Val Thr Phe 195 200 205 Pro Gly Ala Gly Val Thr Met Glu Arg Thr Ile Gln Leu Asn Val Ser 210 215 220 Tyr Ala Pro Gln Lys Val Ala Ile Ser Ile Phe Gln Gly Asn Ser Ala 225 230 235 240 Ala Phe Lys Ile Leu Gln Asn Thr Ser Ser Leu Pro Val Leu Glu Gly 245 250 255 Gln Ala Leu Arg Leu Leu Cys Asp Ala Asp Gly Asn Pro Pro Ala His 260 265 270 Leu Ser Trp Phe Gln Gly Phe Pro Ala Leu Asn Ala Thr Pro Ile Ser 275 280 285 Asn Thr Gly Val Leu Glu Leu Pro Gln Val Gly Ser Ala Glu Glu Gly 290 295 300 Asp Phe Thr Cys Arg Ala Gln His Pro Leu Gly Ser Leu Gln Ile Ser 305 310 315 320 Leu Ser Leu Phe Val His Trp Ser Ser Ala Pro Val Pro Asp Arg His 325 330 335 Ser Phe Arg Pro Pro Cys 340 SEQ ID NO: 7 Sequence length: 342 Sequence type: amino acid Topology: linear Sequence type: protein Sequence: Met Leu Pro Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln 1 5 10 15 Glu Arg Arg Phe Gln Leu Glu Gly Pro Glu Ser Leu Thr Val Gln Glu 20 25 30 Gly Leu Cys Val Leu Val Pro Cys Arg Leu Pro Thr Thr Leu Pro Ala 35 40 45 Ser Tyr Tyr Gly Tyr Gly Tyr Trp Phe Leu Glu Gly Ala Asp Val Pro 50 55 60 Val Ala Thr Asn Asp Pro Asp Glu Glu Val Gln Glu Glu Thr Arg Gly 65 70 75 80 Arg Phe His Leu Leu Trp Asp Pro Arg Arg Lys Asn Cys Ser Leu Ser 85 90 95 Ile Arg Asp Ala Arg Arg Arg Asp Asn Ala Ala Tyr Phe Phe Arg Leu 100 105 110 Lys Ser Lys Trp Met Lys Tyr Gly Tyr Thr Ser Ser Lys Leu Ser Val 115 120 125 Arg Val Met Ala Leu Thr His Arg Pro Asn Ile Ser Ile Pro Gly Thr 130 135 140 Leu Glu Ser Gly His Pro Ser Asn Leu Thr Cys Ser Val Pro Trp Val 145 150 155 160 Cys Glu Gln Gly Thr Pro Pro Ile Phe Ser Trp Met Ser Ala Ala Pro 165 170 175 Thr Ser Leu Gly P ro Arg Thr Thr Gln Ser Ser Val Leu Thr Ile Thr 180 185 190 Pro Arg Pro Gln Asp His Ser Thr Asn Leu Thr Cys Gln Val Thr Phe 195 200 205 Pro Gly Ala Gly Val Thr Met Glu Arg Thr Ile Gln Leu Asn Val Ser 210 215 220 Tyr Ala Pro Gln Lys Val Ala Ile Ser Ile Phe Gln Gly Asn Ser Ala 225 230 235 240 Ala Phe Lys Ile Leu Gln Asn Thr Ser Ser Leu Pro Val Leu Glu Gly 245 250 255 Gln Ala Leu Arg Leu Leu Cys Asp Ala Asp Gly Asn Pro Pro Ala His 260 265 270 Leu Ser Trp Phe Gln Gly Phe Pro Ala Leu Asn Ala Thr Pro Ile Ser 275 280 285 Asn Thr Gly Val Leu Glu Leu Pro Gln Val Gly Ser Ala Glu Glu Gly 290 295 300 Asp Phe Thr Cys Arg Ala Gln His Pro Leu Gly Ser Leu Gln Ile Ser 305 310 315 320 Leu Ser Leu Phe Val His Trp Ser Ser Ala Pro Val Pro Asp Arg His 325 330 335 Ser Phe Arg Pro Pro Cys 340
【０１６０】配列番号：８ 配列の長さ：１０２６ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列： ATGCTACCGC TGCTGCTGCC CCTGCTGTGG GCAGGGGCCC TGGCTCAGGA GCGGAGATTC 60 CAGCTGGAGG GGCCAGAGTC ACTGACGGTG CAGGAGGGTC TGTGCGTCCT CGTACCCTGC 120 AGATTGCCCA CTACCCTTCC AGCCTCGTAC TATGGTTATG GCTACTGGTT CCTGGAAGGG 180 GCTGATGTTC CAGTGGCCAC AAACGACCCA GACGAAGAAG TGCAGGAGGA GACCCGGGGC 240 CGATTCCACC TCCTCTGGGA TCCCAGAAGG AAGAACTGCT CCCTGAGCAT CAGAGATGCC 300 CGGAGGAGGG ACAATGCTGC ATACTTCTTT CGGTTGAAGT CCAAATGGAT GAAATACGGT 360 TATACATCTT CCAAGCTCTC TGTGCGTGTG ATGGCCCTGA CCCACAGGCC CAACATCTCC 420 ATCCCAGGGA CCCTGGAGTC TGGCCATCCC AGCAATCTGA CCTGCTCTGT GCCCTGGGTC 480 TGTGAGCAGG GGACGCCCCC CATCTTCTCC TGGATGTCAG CTGCCCCCAC CTCCCTGGGC 540 CCCAGGACCA CCCAGTCCTC GGTGCTCACA ATCACCCCAC GGCCCCAGGA CCACAGCACC 600 AACCTCACCT GTCAGGTGAC GTTCCCTGGA GCCGGTGTGA CCATGGAGAG AACCATCCAG 660 CTCAATGTCT CCTATGCTCC ACAGAAAGTG GCCATCAGCA TCTTCCAAGG AAACAGCGCA 720 GCCTTCAAAA TCCTGCAAAA CACCTCGTCC CTCCCTGTCC TGGAGGGCCA GGCTCTGCGG 780 CTGCTCTGTG ATGCTGACGG CAACCCCCCT GCACACCTGA GCTGGTTCCA GGGCTTCCCC 840 GCCCTGAACG CCACCCCCAT CTCCAATACC GGGGTCCTGG AGCTGCCTCA AGTAGGGTCT 900 GCAGAAGAAG GAGATTTCAC CTGCCGTGCT CAGCATCCTC TGGGCTCCCT GCAAATCTCT 960 CTGAGTCTCT TTGTGCATTG GTCATCAGCA CCAGTTCCAG ACAGGCATAG TTTCAGACCA 1020 CCCTGC 1026SEQ ID NO: 8 Sequence length: 1026 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence: ATGCTACCGC TGCTGCTGCC CCTGCTGTGG GCAGGGGCCC TGGCTCAGGA GCGGAGATTC 60 CAGCTGGAGG GGCCAGGGTCAGTGACGGTCGG TGTGCGTCCT CGTACCCTGC 120 AGATTGCCCA CTACCCTTCC AGCCTCGTAC TATGGTTATG GCTACTGGTT CCTGGAAGGG 180 GCTGATGTTC CAGTGGCCAC AAACGACCCA GACGAAGAAG TGCAGGAGGA GACCCGGGGC 240 CGATTCCACC TCCTCTGGGA TCCCAGAAGG AAGAACTGCT CCCTGAGCAT CAGAGATGCC 300 CGGAGGAGGG ACAATGCTGC ATACTTCTTT CGGTTGAAGT CCAAATGGAT GAAATACGGT 360 TATACATCTT CCAAGCTCTC TGTGCGTGTG ATGGCCCTGA CCCACAGGCC CAACATCTCC 420 ATCCCAGGGA CCCTGGAGTC TGGCCATCCC AGCAATCTGA CCTGCTCTGT GCCCTGGGTC 480 TGTGAGCAGG GGACGCCCCC CATCTTCTCC TGGATGTCAG CTGCCCCCAC CTCCCTGGGC 540 CCCAGGACCA CCCAGTCCTC GGTGCTCACA ATCACCCCAC GGCCCCAGGA CCACAGCACC 600 AACCTCACCT GTCAGGTGAC GTTCCCTGGA GCCGGTGTGA CCATGGAGAG AACCATCCAG 660 CTCAATGTCT CCTATGCTCC ACAGAAAGTG GCCATCAGCA TCTTCCAA GG AAACAGCGCA 720 GCCTTCAAAA TCCTGCAAAA CACCTCGTCC CTCCCTGTCC TGGAGGGCCA GGCTCTGCGG 780 CTGCTCTGTG ATGCTGACGG CAACCCCCCT GCACACCTGA GCTGGTTCCA GGGCTTCCCC 840 GCCCTGAACG CCACCCCCAT CTCCAATACC GGGGTCCTGG AGCTGCCTCA AGTAGGGTCT 900 GCAGAAGAAG GAGATTTCAC CTGCCGTGCT CAGCATCCTC TGGGCTCCCT GCAAATCTCT 960 CTGAGTCTCT TTGTGCATTG GTCATCAGCA CCAGTTCCAG ACAGGCATAG TTTCAGACCA 1020 CCCTGC 1026
【０１６１】配列番号：９ 配列の長さ：１７４１ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列の特徴： 特徴を表わす記号：CDS 存在位置：２３７．．１２６２ 特徴を決定した方法：Ｅ 配列： GCGGGACACA GTCTCTTCTC CTCTGCTCTT CTTTGGGCAG AGGGTCTCAA AGTTTCCGTC 60 TGCTCTGTGC AGAGGGAGTG GAGCTCCGAG GGCTTGTGGC TTCGCAGTTC CTCTTCTGTG 120 AACAGCCGAG ATCACGCGCT CCTCCCCAGC CACCCGTTCC TCCCCGCAGT CCTTCCCCTC 180 CACTCCCTTC CCCTTCTCTG CTCATGCAGG GAGCCCAGAA AGCCTCCGCC TCAGAG 236 ATG CTA CCG CTG CTG CTG CCC CTG CTG TGG GCA GGG GCC CTG GCT CAG 284 Met Leu Pro Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln 1 5 10 15 GAG CGG AGA TTC CAG CTG GAG GGG CCA GAG TCA CTG ACG GTG CAG GAG 332 Glu Arg Arg Phe Gln Leu Glu Gly Pro Glu Ser Leu Thr Val Gln Glu 20 25 30 GGT CTG TGC GTC CTC GTA CCC TGC AGA TTG CCC ACT ACC CTT CCA GCC 380 Gly Leu Cys Val Leu Val Pro Cys Arg Leu Pro Thr Thr Leu Pro Ala 35 40 45 TCG TAC TAT GGT TAT GGC TAC TGG TTC CTG GAA GGG GCT GAT GTT CCA 428 Ser Tyr Tyr Gly Tyr Gly Tyr Trp Phe Leu Glu Gly Ala Asp Val Pro 50 55 60 GTG GCC ACA AAC GAC CCA GAC GAA GAA GTG CAG GAG GAG ACC CGG GGC 476 Val Ala Thr Asn Asp Pro Asp Glu Glu Val Gln Glu Glu Thr Arg Gly 65 70 75 80 CGA TTC CAC CTC CTC TGG GAT CCC AGA AGG AAG AAC TGC TCC CTG AGC 524 Arg Phe His Leu Leu Trp Asp Pro Arg Arg Lys Asn Cys Ser Leu Ser 85 90 95 ATC AGA GAT GCC CGG AGG AGG GAC AAT GCT GCA TAC TTC TTT CGG TTG 572 Ile Arg Asp Ala Arg Arg Arg Asp Asn Ala Ala Tyr Phe Phe Arg Leu 100 105 110 AAG TCC AAA TGG ATG AAA TAC GGT TAT ACA TCT TCC AAG CTC TCT GTG 620 Lys Ser Lys Trp Met Lys Tyr Gly Tyr Thr Ser Ser Lys Leu Ser Val 115 120 125 CGT GTG ATG GCC CTG ACC CAC AGG CCC AAC ATC TCC ATC CCA GGG ACC 668 Arg Val Met Ala Leu Thr His Arg Pro Asn Ile Ser Ile Pro Gly Thr 130 135 140 CTG GAG TCT GGC CAT CCC AGC AAT CTG ACC TGC TCT GTG CCC TGG GTC 716 Leu Glu Ser Gly His Pro Ser Asn Leu Thr Cys Ser Val Pro Trp Val 145 150 155 160 TGT GAG CAG GGG ACG CCC CCC ATC TTC TCC TGG ATG TCA GCT GCC CCC 764 Cys Glu Gln Gly Thr Pro Pro Ile Phe Ser Trp Met Ser Ala Ala Pro 165 170 175 ACC TCC CTG GGC CCC AGG ACC ACC CAG TCC TCG GTG CTC ACA ATC ACC 812 Thr Ser Leu Gly Pro Arg Thr Thr Gln Ser Ser Val Leu Thr Ile Thr 180 185 190 CCA CGG CCC CAG GAC CAC AGC ACC AAC CTC ACC TGT CAG GTG ACG TTC 860 Pro Arg Pro Gln Asp His Ser Thr Asn Leu Thr Cys Gln Val Thr Phe 195 200 205 CCT GGA GCC GGT GTG ACC ATG GAG AGA ACC ATC CAG CTC AAT GTC TCC 908 Pro Gly Ala Gly Val Thr Met Glu Arg Thr Ile Gln Leu Asn Val Ser 210 215 220 TAT GCT CCA CAG AAA GTG GCC ATC AGC ATC TTC CAA GGA AAC AGC GCA 956 Tyr Ala Pro Gln Lys Val Ala Ile Ser Ile Phe Gln Gly Asn Ser Ala 225 230 235 240 GCC TTC AAA ATC CTG CAA AAC ACC TCG TCC CTC CCT GTC CTG GAG GGC 1004 Ala Phe Lys Ile Leu Gln Asn Thr Ser Ser Leu Pro Val Leu Glu Gly 245 250 255 CAG GCT CTG CGG CTG CTC TGT GAT GCT GAC GGC AAC CCC CCT GCA CAC 1052 Gln Ala Leu Arg Leu Leu Cys Asp Ala Asp Gly Asn Pro Pro Ala His 260 265 270 CTG AGC TGG TTC CAG GGC TTC CCC GCC CTG AAC GCC ACC CCC ATC TCC 1100 Leu Ser Trp Phe Gln Gly Phe Pro Ala Leu Asn Ala Thr Pro Ile Ser 275 280 285 AAT ACC GGG GTC CTG GAG CTG CCT CAA GTA GGG TCT GCA GAA GAA GGA 1148 Asn Thr Gly Val Leu Glu Leu Pro Gln Val Gly Ser Ala Glu Glu Gly 290 295 300 GAT TTC ACC TGC CGT GCT CAG CAT CCT CTG GGC TCC CTG CAA ATC TCT 1196 Asp Phe Thr Cys Arg Ala Gln His Pro Leu Gly Ser Leu Gln Ile Ser 305 310 315 320 CTG AGT CTC TTT GTG CAT TGG TCA TCA GCA CCA GTT CCA GAC AGG CAT 1244 Leu Ser Leu Phe Val His Trp Ser Ser Ala Pro Val Pro Asp Arg His 325 330 335 AGT TTC AGA CCA CCC TGC TGAGGCTGGC CCCATCTCAG AAGATGAGCA 1292 Ser Phe Arg Pro Pro Cys 340 GGAGCTCCAC TACGCTGTCC TACACTTCCA CAAGGTGCAA CCTCAGGAAC CAAAGGTCAC 1352 CGACACTGAG TACTCAGAAA TCAAGATACA CAAGTGAGGA ATTGTCCAAA GCCATAACCT 1412 TGATTGGAGA GAACATGGTA CCTCTCAGTG TATTGGTTAC TAGGGCTGCC ACAGCAATGT 1472 ACCACAAACC GAGTGACATA AACACAGAAC TTTATTTTCG TATAGTTTCA GATGTTAGAG 1532 GTCTGAGAAC AAGGTGTTAT CAGGGTTGGT CCCTTCTAAG GCCTCTCTTG TTGGCTTGTA 1592 GATGGCTGTC TCCTCCTTGT GTCTTCACAT GGTCTTTCCT CTGAGTGTGT TTGTGTCCTA 1652 ATCTTCTCTT CTTATAAAGA CACTAGTCAT ATTGGATTAG GGCCTCCCCA TGACCTAATT 1712 TAAATAAATT AACTATTTAA AGACCCTCC 1741SEQ ID NO: 9 Sequence length: 1741 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence characteristics: Characterizing symbol: CDS Location: 237. . 1262 method to determine the characteristics: E SEQ: GCGGGACACA GTCTCTTCTC CTCTGCTCTT CTTTGGGCAG AGGGTCTCAA AGTTTCCGTC 60 TGCTCTGTGC AGAGGGAGTG GAGCTCCGAG GGCTTGTGGC TTCGCAGTTC CTCTTCTGTG 120 AACAGCCGAG ATCACGCGCT CCTCCCCAGC CACCCGTTCC TCCCCGCAGT CCTTCCCCTC 180 CACTCCCTTC CCCTTCTCTG CTCATGCAGG GAGCCCAGAA AGCCTCCGCC TCAGAG 236 ATG CTA CCG CTG CTG CTG CCC CTG CTG TGG GCA GGG GCC CTG GCT CAG 284 Met Leu Pro Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln 1 5 10 15 GAG CGG AGA TTC CAG CTG GAG GGG CCA GAG TCA CTG ACG GTG CAG GAG 332 Glu Arg Arg Phe Gln Leu Glu Gly Pro Glu Ser Leu Thr Val Gln Glu 20 25 30 GGT CTG TGC GTC CTC GTA CCC TGC AGA TTG CCC ACT ACC CTT CCA GCC 380 Gly Leu Cys Val Leu Val Pro Cys Arg Leu Pro Thr Thr Leu Pro Ala 35 40 45 TCG TAC TAT GGT TAT GGC TAC TGG TTC CTG GAA GGG GCT GAT GTT CCA 428 Ser Tyr Tyr Gly Tyr Gly Tyr Trp Phe Leu Glu Gly Ala Asp Val Pro 50 55 60 GTG GCC ACA AAC GAC CCA GAC GAA GAA GTG CAG GAG GAG ACC CGG GGC 476 Val Ala Thr Asn Asp Pro Asp Glu Glu Val Gln Glu Glu Thr Arg Gly 65 70 75 80 CGA TTC CAC CTC CTC TGG GAT CCC AGA AGG AAG AAC TGC TCC CTG AGC 524 Arg Phe His Leu Leu Trp Asp Pro Arg Arg Lys Asn Cys Ser Leu Ser 85 90 95 ATC AGA GAT GCC CGG AGG AGG GAC AAT GCT GCA TAC TTC TTT CGG TTG 572 Ile Arg Asp Ala Arg Arg Arg Asp Asn Ala Ala Tyr Phe Phe Arg Leu 100 105 110 AAG TCC AAA TGG ATG AAA TAC GGT TAT ACA TCT TCC AAG CTC TCT GTG 620 Lys Ser Lys Trp Met Lys Tyr Gly Tyr Thr Ser Ser Lys Leu Ser Val 115 120 125 CGT GTG ATG GCC CTG ACC CAC AGG CCC AAC ATC TCC ATC CCA GGG ACC 668 Arg Val Met Ala Leu Thr His Arg Pro Asn Ile Ser Ile Pro Gly Thr 130 135 140 CTG GAG TCT GGC CAT CCC AGC AAT CTG ACC TGC TCT GTG CCC TGG GTC 716 Leu Glu Ser Gly His Pro Ser Asn Leu Thr Cys Ser Val Pro Trp Val 145 150 155 160 TGT GAG CAG GGG ACG CCC CCC ATC TTC TCC TGG ATG TCA GCT GCC CCC 764 Cys Glu Gln Gly Thr Pro Pro Ile Phe Ser Trp Met Ser Ala Ala Pro 165 170 175 ACC TCC CTG GGC CCC AGG ACC ACC CAG TCC TCG GTG CTC ACA ATC ACC 812 Thr Ser Leu Gly Pro Arg Th r Thr Gln Ser Ser Val Leu Thr Ile Thr 180 185 190 CCA CGG CCC CAG GAC CAC AGC ACC AAC CTC ACC TGT CAG GTG ACG TTC 860 Pro Arg Pro Gln Asp His Ser Thr Asn Leu Thr Cys Gln Val Thr Phe 195 200 205 CCT GGA GCC GGT GTG ACC ATG GAG AGA ACC ATC CAG CTC AAT GTC TCC 908 Pro Gly Ala Gly Val Thr Met Glu Arg Thr Ile Gln Leu Asn Val Ser 210 215 220 TAT GCT CCA CAG AAA GTG GCC ATC AGC ATC TTC CAA GGA AAC AGC GCA 956 Tyr Ala Pro Gln Lys Val Ala Ile Ser Ile Phe Gln Gly Asn Ser Ala 225 230 235 240 GCC TTC AAA ATC CTG CAA AAC ACC TCG TCC CTC CCT GTC CTG GAG GGC 1004 Ala Phe Lys Ile Leu Gln Asn Thr Ser Ser Leu Pro Val Leu Glu Gly 245 250 255 CAG GCT CTG CGG CTG CTC TGT GAT GCT GAC GGC AAC CCC CCT GCA CAC 1052 Gln Ala Leu Arg Leu Leu Cys Asp Ala Asp Gly Asn Pro Pro Ala His 260 265 270 CTG AGC TGG TTC CAG GGC TTC CCC GCC CTG AAC GCC ACC CCC ATC TCC 1100 Leu Ser Trp Phe Gln Gly Phe Pro Ala Leu Asn Ala Thr Pro Ile Ser 275 280 285 AAT ACC GGG GTC CTG GAG CTG CCT CAA GTA GGG TCT GCA GAA GAA GGA 1148 Asn Thr G ly Val Leu Glu Leu Pro Gln Val Gly Ser Ala Glu Glu Gly 290 295 300 GAT TTC ACC TGC CGT GCT CAG CAT CCT CTG GGC TCC CTG CAA ATC TCT 1196 Asp Phe Thr Cys Arg Ala Gln His Pro Leu Gly Ser Leu Gln Ile Ser 305 310 315 320 CTG AGT CTC TTT GTG CAT TGG TCA TCA GCA CCA GTT CCA GAC AGG CAT 1244 Leu Ser Leu Phe Val His Trp Ser Ser Ala Pro Val Pro Asp Arg His 325 330 335 AGT TTC AGA CCA CCC TGC TGAGGCTGGC CCCATCTCAG AAGATGCA Ser Phe Arg Pro Pro Cys 340 GGAGCTCCAC TACGCTGTCC TACACTTCCA CAAGGTGCAA CCTCAGGAAC CAAAGGTCAC 1352 CGACACTGAG TACTCAGAAA TCAAGATACA CAAGTGAGGA ATTGTCCAAA GCCATAACCT 1412 TGATTGGAGA GAACATGGTA CCTCTCAGTG TATTGGTTAC TAGGGCTGCC ACAGCAATGT 1472 ACCACAAACC GAGTGACATA AACACAGAAC TTTATTTTCG TATAGTTTCA GATGTTAGAG 1532 GTCTGAGAAC AAGGTGTTAT CAGGGTTGGT CCCTTCTAAG GCCTCTCTTG TTGGCTTGTA 1592 GATGGCTGTC TCCTCCTTGT GTCTTCACAT GGTCTTTCCT CTGAGTGTGT TTGTGTCCTA 1652 ATCTTCTCTT CTTATAAAGA CACTAGTCAT ATTGGATTAG GGCCTCCCCA TGACCTAATT 1712 TAAATAAATT AACTATTTAA AGACCCTCC 1741
【０１６２】配列番号：１０ 配列の長さ：１３２ 配列の型：アミノ酸 トポロジー：直線状 配列の種類：蛋白 配列： Met Val Glu Ala Phe Cys Ala Thr Trp Lys Leu Thr Asn Ser Gln Asn 1 5 10 15 Phe Asp Glu Tyr Met Lys Ala Leu Gly Val Gly Phe Ala Thr Arg Gln 20 25 30 Val Gly Asn Val Thr Lys Pro Thr Val Ile Ile Ser Gln Glu Gly Asp 35 40 45 Lys Val Val Ile Arg Thr Leu Ser Thr Phe Lys Asn Thr Glu Ile Ser 50 55 60 Phe Gln Leu Gly Glu Glu Phe Asp Glu Thr Thr Ala Asp Asp Arg Asn 65 70 75 80 Cys Lys Ser Val Val Ser Leu Asp Gly Asp Lys Leu Val His Ile Gln 85 90 95 Lys Trp Asp Gly Lys Glu Thr Asn Phe Val Arg Glu Ile Lys Asp Gly 100 105 110 Lys Met Val Met Thr Leu Thr Phe Gly Asp Val Val Ala Val Arg His 115 120 125 Tyr Glu Lys Ala 130 SEQ ID NO: 10 Sequence length: 132 Sequence type: amino acid Topology: Linear Sequence type: Protein Sequence: Met Val Glu Ala Phe Cys Ala Thr Trp Lys Leu Thr Asn Ser Gln Asn 1 5 10 15 Phe Asp Glu Tyr Met Lys Ala Leu Gly Val Gly Phe Ala Thr Arg Gln 20 25 30 Val Gly Asn Val Thr Lys Pro Thr Val Ile Ile Ser Gln Glu Gly Asp 35 40 45 Lys Val Val Ile Arg Thr Leu Ser Thr Phe Lys Asn Thr Glu Ile Ser 50 55 60 Phe Gln Leu Gly Glu Glu Phe Asp Glu Thr Thr Ala Asp Asp Arg Asn 65 70 75 80 Cys Lys Ser Val Val Ser Leu Asp Gly Asp Lys Leu Val His Ile Gln 85 90 95 Lys Trp Asp Gly Lys Glu Thr Asn Phe Val Arg Glu Ile Lys Asp Gly 100 105 110 Lys Met Val Met Thr Leu Thr Phe Gly Asp Val Val Ala Val Arg His 115 120 125 Tyr Glu Lys Ala 130
【０１６３】配列番号：１１ 配列の長さ：３９６ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列： ATGGTGGAGG CTTTCTGTGC TACCTGGAAG CTGACCAACA GTCAGAACTT TGATGAGTAC 60 ATGAAGGCTC TAGGCGTGGG CTTTGCCACT AGGCAGGTGG GAAATGTGAC CAAACCAACG 120 GTAATTATCA GTCAAGAAGG AGACAAAGTG GTCATCAGGA CTCTCAGCAC ATTCAAGAAC 180 ACGGAGATTA GTTTCCAGCT GGGAGAAGAG TTTGATGAAA CCACTGCAGA TGATAGAAAC 240 TGTAAGTCTG TTGTTAGCCT GGATGGAGAC AAACTTGTTC ACATACAGAA ATGGGATGGC 300 AAAGAAACAA ATTTTGTAAG AGAAATTAAG GATGGCAAAA TGGTTATGAC CCTTACTTTT 360 GGTGATGTGG TTGCTGTTCG CCACTATGAG AAGGCA 396SEQ ID NO: 11 Sequence length: 396 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence: ATGGTGGAGG CTTTCTGTGC TACCTGGAAG CTGACCAACA GTCAGAACTT TGATGAGAGTAC 60 ATGAAGGCTC TAGGCGTGGG CTTTGCCAGAGGCGT GAAATGTGAC CAAACCAACG 120 GTAATTATCA GTCAAGAAGG AGACAAAGTG GTCATCAGGA CTCTCAGCAC ATTCAAGAAC 180 ACGGAGATTA GTTTCCAGCT GGGAGAAGAG TTTGATGAAA CCACTGCAGA TGATAGAAAC 240 TGTAAGTCTG TTGTTAGCCT GGATGGAGAC AAACTTGTTC ACATACAGAA ATGGGATGGC 300 AAAGAAACAA ATTTTGTAAG AGAAATTAAG GATGGCAAAA TGGTTATGAC CCTTACTTTT 360 GGTGATGTGG TTGCTGTTCG CCACTATGAG AAGGCA 396
【０１６４】配列番号：１２ 配列の長さ：７５４ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列の特徴： 特徴を表わす記号：CDS 存在位置：５２．．４４８ 特徴を決定した方法：Ｅ 配列： ATTAGACCAG AAGATCCCCG CTCCTGTCTC TAAAGAGGGG AAAGGGCAAG G ATG GTG 57 Met Val 1 GAG GCT TTC TGT GCT ACC TGG AAG CTG ACC AAC AGT CAG AAC TTT GAT 105 Glu Ala Phe Cys Ala Thr Trp Lys Leu Thr Asn Ser Gln Asn Phe Asp 5 10 15 GAG TAC ATG AAG GCT CTA GGC GTG GGC TTT GCC ACT AGG CAG GTG GGA 153 Glu Tyr Met Lys Ala Leu Gly Val Gly Phe Ala Thr Arg Gln Val Gly 20 25 30 AAT GTG ACC AAA CCA ACG GTA ATT ATC AGT CAA GAA GGA GAC AAA GTG 201 Asn Val Thr Lys Pro Thr Val Ile Ile Ser Gln Glu Gly Asp Lys Val 35 40 45 50 GTC ATC AGG ACT CTC AGC ACA TTC AAG AAC ACG GAG ATT AGT TTC CAG 249 Val Ile Arg Thr Leu Ser Thr Phe Lys Asn Thr Glu Ile Ser Phe Gln 55 60 65 CTG GGA GAA GAG TTT GAT GAA ACC ACT GCA GAT GAT AGA AAC TGT AAG 297 Leu Gly Glu Glu Phe Asp Glu Thr Thr Ala Asp Asp Arg Asn Cys Lys 70 75 80 TCT GTT GTT AGC CTG GAT GGA GAC AAA CTT GTT CAC ATA CAG AAA TGG 345 Ser Val Val Ser Leu Asp Gly Asp Lys Leu Val His Ile Gln Lys Trp 85 90 95 GAT GGC AAA GAA ACA AAT TTT GTA AGA GAA ATT AAG GAT GGC AAA ATG 393 Asp Gly Lys Glu Thr Asn Phe Val Arg Glu Ile Lys Asp Gly Lys Met 100 105 110 GTT ATG ACC CTT ACT TTT GGT GAT GTG GTT GCT GTT CGC CAC TAT GAG 441 Val Met Thr Leu Thr Phe Gly Asp Val Val Ala Val Arg His Tyr Glu 115 120 125 130 AAG GCA T AAAAATGTTC CTGGTCGGGG CTTGGAAGAG CTCTTCAGTT TTTCTGTTTC 498 Lys Ala CTCAAGTCTC AGTGCTATCC TATTACAACA TGGCTGATCA TTAATTAGAA GGTTATCCTT 558 GGTGTGGAGG TGGAAAATGG TGATTTAAAA ACTTGTTACT CCAAGCAACT TGCCCAATTT 618 TAATCTGAAA ATTTATCATG TTTTATAATT TGAATTAAAG TTTTGTCCCC CCCCCCCTTT 678 TTTTTATAAA CAAGTGAATA CATTTTATAA TTTCTTTTGG AATGTAAATC AAATTTGAAT 738 AAAAATCTTA CACGTG 754SEQ ID NO: 12 Sequence length: 754 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence characteristics: Characterizing symbol: CDS Location: 52. . 448 Method for Characterization: E Sequence: ATTAGACCAG AAGATCCCCG CTCCTGTCTC TAAAGAGGGG AAAGGGCAAG G ATG GTG 57 Met Val 1 GAG GCT TTC TGT GCT ACC TGG AAG CTG ACC AAC AGT CAG AAC TTT GAT 105 Glu Ala Phe Cys Ala Thr Trp Lys Ser Gln Asn Phe Asp 5 10 15 GAG TAC ATG AAG GCT CTA GGC GTG GGC TTT GCC ACT AGG CAG GTG GGA 153 Glu Tyr Met Lys Ala Leu Gly Val Gly Phe Ala Thr Arg Gln Val Gly 20 25 30 AAT GTG ACC AAA CCA ACG GTA ATT ATC AGT CAA GAA GGA GAC AAA GTG 201 Asn Val Thr Lys Pro Thr Val Ile Ile Ser Gln Glu Gly Asp Lys Val 35 40 45 50 GTC ATC AGG ACT CTC AGC ACA TTC AAG AAC ACG GAG ATT AGT TTC CAG 249 Val Ile Arg Thr Leu Ser Thr Phe Lys Asn Thr Glu Ile Ser Phe Gln 55 60 65 CTG GGA GAA GAG TTT GAT GAA ACC ACT GCA GAT GAT AGA AAC TGT AAG 297 Leu Gly Glu Glu Phe Asp Glu Thr Thr Ala Asp Asp Arg Asn Cys Lys 70 75 80 TCT GTT GTT AGC CTG GAT GGA GAC AAA CTT GTT CAC ATA CAG AAA TGG 345 Ser Val Val Ser Leu Asp Gly Asp Lys Leu Val His Ile Gln Lys Trp 85 90 95 GAT GGC AAA GAA ACA AAT TTT GTA AGA GAA ATT AAG GAT GGC AAA ATG 393 Asp Gly Lys Glu Thr Asn Phe Val Arg Glu Ile Lys Asp Gly Lys Met 100 105 110 GTT ATG ACC CTT ACT TTT GGT GAT GTG GTT GCT GTT CGC CAC TAT GAG 441 Val Met Thr Leu Thr Phe Gly Asp Val Val Ala Val Arg His Tyr Glu 115 120 125 130 AAG GCA T AAAAATGTTC CTGGTCGGGG CTTGGAAGAG CTCTTCAGTT TTTCTGTTTC 498 Lys Ala CTCAAGTCTC AGTGCTATCC TATTACAACA TGGCTGATCA TTAATTAGAA GGTTATCCTT 558 GGTGTGGAGG TGGAAAATGG TGATTTAAAA ACTTGTTACT CCAAGCAACT TGCCCAATTT 618 TAATCTGAAA ATTTATCATG TTTTATAATT TGAATTAAAG TTTTGTCCCC CCCCCCCTTT 678 TTTTTATAAA CAAGTGAATA CATTTTATAA TTTCTTTTGG AATGTAAATC AAATTTGAAT 738 AAAAATCTTA CACGTG 754
【０１６５】配列番号：１３ 配列の長さ：５６１ 配列の型：アミノ酸 トポロジー：直線状 配列の種類：蛋白 配列： Met Asn Ser Ser Leu Thr Ala Gln Arg Arg Gly Ser Asp Ala Glu Leu 1 5 10 15 Gly Pro Trp Val Met Ala Ala Arg Ser Lys Asp Ala Ala Pro Ser Gln 20 25 30 Arg Asp Gly Leu Leu Pro Val Lys Val Glu Glu Asp Ser Pro Gly Ser 35 40 45 Trp Glu Pro Asn Tyr Pro Ala Ala Ser Pro Asp Pro Glu Thr Ser Arg 50 55 60 Leu His Phe Arg Gln Leu Arg Tyr Gln Glu Val Ala Gly Pro Glu Glu 65 70 75 80 Ala Leu Ser Arg Leu Arg Glu Leu Cys Arg Arg Trp Leu Arg Pro Glu 85 90 95 Leu Leu Ser Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe 100 105 110 Leu Thr Ile Leu Pro Glu Glu Leu Gln Ala Trp Val Arg Glu His Cys 115 120 125 Pro Glu Ser Gly Glu Glu Ala Val Ala Val Val Arg Ala Leu Gln Arg 130 135 140 Ala Leu Asp Gly Thr Ser Ser Gln Gly Met Val Thr Phe Glu Asp Thr 145 150 155 160 Ala Val Ser Leu Thr Trp Glu Glu Trp Glu Arg Leu Asp Pro Ala Arg 165 170 175 Arg Asp Phe Cys Arg Glu Ser Ala Gln Lys Asp Ser Gly Ser Thr Val 180 185 190 Pro Pro Ser Leu Glu Ser Arg Val Glu Asn Lys Glu Leu Ile Pro Met 195 200 205 Gln Gln Ile Leu Glu Glu Ala Glu Pro Gln Gly Gln Leu Gln Glu Ala 210 215 220 Phe Gln Gly Lys Arg Pro Leu Phe Ser Lys Cys Gly Ser Thr His Glu 225 230 235 240 Asp Arg Val Glu Lys Gln Ser Gly Asp Pro Leu Pro Leu Lys Leu Glu 245 250 255 Asn Ser Pro Glu Ala Glu Gly Leu Asn Ser Ile Ser Asp Val Asn Lys 260 265 270 Asn Gly Ser Ile Glu Gly Glu Asp Ser Lys Asn Asn Glu Leu Gln Asn 275 280 285 Ser Ala Arg Cys Ser Asn Leu Val Leu Cys Gln His Ile Pro Lys Ala 290 295 300 Glu Arg Pro Thr Asp Ser Glu Glu His Gly Asn Lys Cys Lys Gln Ser 305 310 315 320 Phe His Met Val Thr Trp His Val Leu Lys Pro His Lys Ser Asp Ser 325 330 335 Gly Asp Ser Phe His His Ser Ser Leu Phe Glu Thr Gln Arg Gln Leu 340 345 350 His Glu Glu Arg Pro Tyr Lys Cys Gly Asn Cys Gly Lys Ser Phe Lys 355 360 365 Gln Arg Ser Asp Leu Phe Arg His Gln Arg Ile His Thr Gly Glu Lys 370 375 380 Pro Tyr Gly Cys Gln Glu Cys Gly Lys Ser Phe Ser Gln Ser Ala Ala 385 390 395 400 Leu Thr Lys His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Thr Cys 405 410 415 Leu Lys Cys Gly Glu Arg Phe Arg Gln Asn Ser His Leu Asn Arg His 420 425 430 Gln Ser Thr His Ser Arg Asp Lys His Phe Lys Cys Glu Glu Cys Gly 435 440 445 Glu Thr Cys His Ile Ser Asn Leu Phe Arg His Gln Arg Leu His Lys 450 455 460 Gly Glu Arg Pro Tyr Lys Cys Glu Glu Cys Glu Lys Ser Phe Lys Gln 465 470 475 480 Arg Ser Asp Leu Phe Lys His His Arg Ile His Thr Gly Glu Lys Pro 485 490 495 Tyr Gly Cys Ser Val Cys Gly Lys Arg Phe Asn Gln Ser Ala Thr Leu 500 505 510 Ile Lys His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Leu 515 520 525 Glu Cys Gly Glu Arg Phe Arg Gln Ser Thr His Leu Ile Arg His Gln 530 535 540 Arg Ile His Gln Asn Lys Val Leu Ser Ala Gly Arg Gly Gly Ser Arg 545 550 555 560 LeuSEQ ID NO: 13 Sequence length: 561 Sequence type: amino acid Topology: Linear Sequence type: Protein Sequence: Met Asn Ser Ser Leu Thr Ala Gln Arg Arg Gly Ser Asp Ala Glu Leu 1510 15 Gly Pro Trp Val Met Ala Ala Arg Ser Lys Asp Ala Ala Pro Ser Gln 20 25 30 Arg Asp Gly Leu Leu Pro Val Lys Val Glu Glu Asp Ser Pro Gly Ser 35 40 45 Trp Glu Pro Asn Tyr Pro Ala Ala Ser Pro Asp Pro Glu Thr Ser Arg 50 55 60 Leu His Phe Arg Gln Leu Arg Tyr Gln Glu Val Ala Gly Pro Glu Glu 65 70 75 80 Ala Leu Ser Arg Leu Arg Glu Leu Cys Arg Arg Trp Leu Arg Pro Glu 85 90 95 Leu Leu Ser Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe 100 105 110 Leu Thr Ile Leu Pro Glu Glu Leu Gln Ala Trp Val Arg Glu His Cys 115 120 125 Pro Glu Ser Gly Glu Glu Ala Val Ala Val Val Arg Ala Leu Gln Arg 130 135 140 Ala Leu Asp Gly Thr Ser Ser Gln Gly Met Val Thr Phe Glu Asp Thr 145 150 155 160 Ala Val Ser Leu Thr Trp Glu Glu Trp Glu Arg Leu Asp Pro Ala Arg 165 170 175 Arg Asp Phe Cys Arg Glu Ser Ala Gln Lys Asp Ser Gly Ser Thr Val 180 185 190 Pro Pro Ser Leu Glu Ser Arg Val Glu Asn Lys Glu Leu Ile Pro Met 195 200 205 Gln Gln Ile Leu Glu Glu Ala Glu Pro Gln Gly Gln Leu Gln Glu Ala 210 215 220 Phe Gln Gly Lys Arg Pro Leu Phe Ser Lys Cys Gly Ser Thr His Glu 225 230 235 240 Asp Arg Val Glu Lys Gln Ser Gly Asp Pro Leu Pro Leu Lys Leu Glu 245 250 255 Asn Ser Pro Glu Ala Glu Gly Leu Asn Ser Ile Ser Asp Val Asn Lys 260 265 270 Asn Gly Ser Ile Glu Gly Glu Asp Ser Lys Asn Asn Glu Leu Gln Asn 275 280 285 Ser Ala Arg Cys Ser Asn Leu Val Leu Cys Gln His Ile Pro Lys Ala 290 295 300 Glu Arg Pro Thr Asp Ser Glu Glu His Gly Asn Lys Cys Lys Gln Ser 305 310 315 320 Phe His Met Val Thr Trp His Val Leu Lys Pro His Lys Ser Asp Ser 325 330 335 Gly Asp Ser Phe His His Ser Ser Leu Phe Glu Thr Gln Arg Gln Leu 340 345 350 His Glu Glu Arg Pro Tyr Lys Cys Gly Asn Cys Gly Lys Ser Phe Lys 355 360 365 Gln Arg Ser Asp Leu Phe Arg His Gln Arg Ile His Thr Gly Glu Lys 370 375 380 Pro Tyr Gly Cys Gl n Glu Cys Gly Lys Ser Phe Ser Gln Ser Ala Ala 385 390 395 400 Leu Thr Lys His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Thr Cys 405 410 415 Leu Lys Cys Gly Glu Arg Phe Arg Gln Asn Ser His Leu Asn Arg His 420 425 430 Gln Ser Thr His Ser Arg Asp Lys His Phe Lys Cys Glu Glu Cys Gly 435 440 445 Glu Thr Cys His Ile Ser Asn Leu Phe Arg His Gln Arg Leu His Lys 450 455 460 Gly Glu Arg Pro Tyr Lys Cys Glu Glu Cys Glu Lys Ser Phe Lys Gln 465 470 475 480 Arg Ser Asp Leu Phe Lys His His Arg Ile His Thr Gly Glu Lys Pro 485 490 495 Tyr Gly Cys Ser Val Cys Gly Lys Arg Phe Asn Gln Ser Ala Thr Leu 500 505 510 Ile Lys His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Leu 515 520 525 Glu Cys Gly Glu Arg Phe Arg Gln Ser Thr His Leu Ile Arg His Gln 530 535 540 Arg Ile His Gln Asn Lys Val Leu Ser Ala Gly Arg Gly Gly Ser Arg 545 550 555 560 Leu
【０１６６】配列番号：１４ 配列の長さ：１６８３ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列： ATGAATTCCA GCTTGACCGC CCAGAGGCGC GGCAGTGACG CCGAGTTGGG ACCCTGGGTG 60 ATGGCTGCGA GGTCCAAGGA CGCGGCGCCG TCCCAACGCG ACGGACTTTT GCCCGTGAAA 120 GTGGAGGAAG ACTCACCCGG AAGTTGGGAG CCCAACTATC CCGCGGCTTC GCCGGACCCC 180 GAAACTTCTC GACTGCACTT TAGGCAGCTG CGTTACCAGG AGGTGGCTGG ACCGGAAGAG 240 GCGCTGAGCC GGCTCCGAGA ACTCTGTCGT CGGTGGCTGA GACCCGAGCT GCTCTCCAAG 300 GAGCAGATCC TGGAGCTGCT GGTGCTGGAG CAGTTCCTCA CCATCCTGCC CGAGGAGCTT 360 CAAGCCTGGG TGCGAGAGCA CTGCCCAGAG AGCGGGGAGG AGGCGGTGGC CGTGGTGCGG 420 GCTCTGCAGC GAGCGCTCGA TGGAACCTCA TCCCAGGGGA TGGTGACTTT CGAGGACACG 480 GCTGTGTCTC TAACCTGGGA GGAGTGGGAG CGCCTGGACC CAGCACGGAG GGACTTCTGC 540 AGAGAGAGTG CGCAGAAGGA TTCCGGGAGC ACAGTTCCGC CGAGTTTGGA AAGCAGAGTG 600 GAGAACAAAG AGTTGATTCC AATGCAACAA ATTTTAGAAG AAGCGGAGCC ACAGGGGCAA 660 CTACAAGAAG CGTTCCAGGG GAAGCGCCCC CTGTTTTCTA AGTGTGGCAG TACCCATGAG 720 GACAGGGTGG AAAAGCAGTC CGGAGACCCC TTGCCCCTGA AACTTGAAAA TTCTCCTGAA 780 GCAGAAGGAC TCAACAGCAT CTCAGATGTC AATAAGAATG GTTCCATAGA AGGGGAAGAC 840 TCTAAAAATA ATGAATTGCA GAACAGTGCC AGGTGTTCCA ACCTTGTTCT ATGTCAGCAC 900 ATCCCGAAAG CAGAGAGGCC CACTGACAGT GAGGAACACG GGAACAAGTG CAAGCAAAGT 960 TTCCACATGG TGACGTGGCA CGTGCTGAAA CCTCACAAGT CTGACAGTGG AGACAGTTTC 1020 CATCATTCCA GCCTTTTTGA GACCCAGAGG CAGCTCCATG AAGAAAGACC TTATAAATGT 1080 GGTAACTGTG GGAAGAGTTT CAAACAACGC TCTGACCTCT TTAGACACCA GAGAATCCAC 1140 ACAGGTGAGA AACCCTATGG CTGCCAAGAA TGTGGGAAAA GCTTCAGCCA GAGTGCTGCC 1200 CTGACCAAGC ACCAGAGGAC ACACACAGGC GAGAAGCCGT ACACCTGTCT GAAATGTGGG 1260 GAGCGCTTCA GGCAGAATTC ACACCTAAAT CGTCATCAAA GTACCCACAG TAGAGACAAA 1320 CATTTTAAAT GTGAGGAATG CGGGGAAACC TGTCATATTT CCAACCTTTT TAGACATCAG 1380 AGACTACATA AAGGGGAAAG ACCCTATAAG TGTGAAGAAT GCGAGAAGAG CTTCAAACAG 1440 CGCTCTGACC TCTTTAAACA CCACAGAATC CACACTGGGG AGAAGCCCTA TGGATGTTCC 1500 GTCTGTGGGA AACGCTTCAA TCAGAGTGCA ACCCTCATTA AACACCAGAG AATTCACACT 1560 GGGGAAAAGC CTTACAAATG TCTTGAATGT GGGGAAAGAT TTAGACAAAG TACACACCTT 1620 ATCCGACACC AAAGAATTCA TCAAAATAAA GTGCTGTCGG CTGGGCGTGG TGGCTCGCGC 1680 CTG 1683SEQ ID NO: 14 Sequence length: 1683 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence: ATGAATTCCA GCTTGACCGC CCAGAGGCGC GGCAGTGACG CCGAGTTGGG ACCCTGGGTG 60 ATGGCTGCGA GGTCCAGCGA TCCGCGGCCGTC ACGGACTTTT GCCCGTGAAA 120 GTGGAGGAAG ACTCACCCGG AAGTTGGGAG CCCAACTATC CCGCGGCTTC GCCGGACCCC 180 GAAACTTCTC GACTGCACTT TAGGCAGCTG CGTTACCAGG AGGTGGCTGG ACCGGAAGAG 240 GCGCTGAGCC GGCTCCGAGA ACTCTGTCGT CGGTGGCTGA GACCCGAGCT GCTCTCCAAG 300 GAGCAGATCC TGGAGCTGCT GGTGCTGGAG CAGTTCCTCA CCATCCTGCC CGAGGAGCTT 360 CAAGCCTGGG TGCGAGAGCA CTGCCCAGAG AGCGGGGAGG AGGCGGTGGC CGTGGTGCGG 420 GCTCTGCAGC GAGCGCTCGA TGGAACCTCA TCCCAGGGGA TGGTGACTTT CGAGGACACG 480 GCTGTGTCTC TAACCTGGGA GGAGTGGGAG CGCCTGGACC CAGCACGGAG GGACTTCTGC 540 AGAGAGAGTG CGCAGAAGGA TTCCGGGAGC ACAGTTCCGC CGAGTTTGGA AAGCAGAGTG 600 GAGAACAAAG AGTTGATTCC AATGCAACAA ATTTTAGAAG AAGCGGAGCC ACAGGGGCAA 660 CTACAAGAAG CGTTCCAGGG GAAGCGCCCCGTGTTC GGCAG TACCCATGAG 720 GACAGGGTGG AAAAGCAGTC CGGAGACCCC TTGCCCCTGA AACTTGAAAA TTCTCCTGAA 780 GCAGAAGGAC TCAACAGCAT CTCAGATGTC AATAAGAATG GTTCCATAGA AGGGGAAGAC 840 TCTAAAAATA ATGAATTGCA GAACAGTGCC AGGTGTTCCA ACCTTGTTCT ATGTCAGCAC 900 ATCCCGAAAG CAGAGAGGCC CACTGACAGT GAGGAACACG GGAACAAGTG CAAGCAAAGT 960 TTCCACATGG TGACGTGGCA CGTGCTGAAA CCTCACAAGT CTGACAGTGG AGACAGTTTC 1020 CATCATTCCA GCCTTTTTGA GACCCAGAGG CAGCTCCATG AAGAAAGACC TTATAAATGT 1080 GGTAACTGTG GGAAGAGTTT CAAACAACGC TCTGACCTCT TTAGACACCA GAGAATCCAC 1140 ACAGGTGAGA AACCCTATGG CTGCCAAGAA TGTGGGAAAA GCTTCAGCCA GAGTGCTGCC 1200 CTGACCAAGC ACCAGAGGAC ACACACAGGC GAGAAGCCGT ACACCTGTCT GAAATGTGGG 1260 GAGCGCTTCA GGCAGAATTC ACACCTAAAT CGTCATCAAA GTACCCACAG TAGAGACAAA 1320 CATTTTAAAT GTGAGGAATG CGGGGAAACC TGTCATATTT CCAACCTTTT TAGACATCAG 1380 AGACTACATA AAGGGGAAAG ACCCTATAAG TGTGAAGAAT GCGAGAAGAG CTTCAAACAG 1440 CGCTCTGACC TCTTTAAACA CCACAGAATC CACACTGGGG AGAAGCCCTA TGGATGTTCC 1500 GTCTGTGGGA AACGCTTCAA TCAGAGTGCA ACCCTCATTA AACACCAGAG AATTC ACACT 1560 GGGGAAAAGC CTTACAAATG TCTTGAATGT GGGGAAAGAT TTAGACAAAG TACACACCTT 1620 ATCCGACACC AAAGAATTCA TCAAAATAAA GTGCTGTCTCCTCTGCGCGTGG TGGCTCGCGC 1680 CTG 1683
【０１６７】配列番号：１５ 配列の長さ：２１６８ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列の特徴： 特徴を表わす記号：CDS 存在位置：１７２．．１８５７ 特徴を決定した方法：Ｅ 配列： CGAGAGAGTT GTAGGCGCAA AGCTGAGGAA AGGAGAGTGT GGAGAGGGGC CTGGTGTGGT 60 GGGGCCCGGT GTTTGGGACC GGAGGGTGTT GACGGCTGAT GAGTTCCTTG GGTTTGCTCT 120 TTCTTCACCT GAAAAGAAGA CTCCAGGAAG GGCAGCACAT GCCGGAGAAA G ATG AAT 177 Met Asn 1 TCC AGC TTG ACC GCC CAG AGG CGC GGC AGT GAC GCC GAG TTG GGA CCC 225 Ser Ser Leu Thr Ala Gln Arg Arg Gly Ser Asp Ala Glu Leu Gly Pro 5 10 15 TGG GTG ATG GCT GCG AGG TCC AAG GAC GCG GCG CCG TCC CAA CGC GAC 273 Trp Val Met Ala Ala Arg Ser Lys Asp Ala Ala Pro Ser Gln Arg Asp 20 25 30 GGA CTT TTG CCC GTG AAA GTG GAG GAA GAC TCA CCC GGA AGT TGG GAG 321 Gly Leu Leu Pro Val Lys Val Glu Glu Asp Ser Pro Gly Ser Trp Glu 35 40 45 50 CCC AAC TAT CCC GCG GCT TCG CCG GAC CCC GAA ACT TCT CGA CTG CAC 369 Pro Asn Tyr Pro Ala Ala Ser Pro Asp Pro Glu Thr Ser Arg Leu His 55 60 65 TTT AGG CAG CTG CGT TAC CAG GAG GTG GCT GGA CCG GAA GAG GCG CTG 417 Phe Arg Gln Leu Arg Tyr Gln Glu Val Ala Gly Pro Glu Glu Ala Leu 70 75 80 AGC CGG CTC CGA GAA CTC TGT CGT CGG TGG CTG AGA CCC GAG CTG CTC 465 Ser Arg Leu Arg Glu Leu Cys Arg Arg Trp Leu Arg Pro Glu Leu Leu 85 90 95 TCC AAG GAG CAG ATC CTG GAG CTG CTG GTG CTG GAG CAG TTC CTC ACC 513 Ser Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe Leu Thr 100 105 110 ATC CTG CCC GAG GAG CTT CAA GCC TGG GTG CGA GAG CAC TGC CCA GAG 561 Ile Leu Pro Glu Glu Leu Gln Ala Trp Val Arg Glu His Cys Pro Glu 115 120 125 130 AGC GGG GAG GAG GCG GTG GCC GTG GTG CGG GCT CTG CAG CGA GCG CTC 609 Ser Gly Glu Glu Ala Val Ala Val Val Arg Ala Leu Gln Arg Ala Leu 135 140 145 GAT GGA ACC TCA TCC CAG GGG ATG GTG ACT TTC GAG GAC ACG GCT GTG 657 Asp Gly Thr Ser Ser Gln Gly Met Val Thr Phe Glu Asp Thr Ala Val 150 155 160 TCT CTA ACC TGG GAG GAG TGG GAG CGC CTG GAC CCA GCA CGG AGG GAC 705 Ser Leu Thr Trp Glu Glu Trp Glu Arg Leu Asp Pro Ala Arg Arg Asp 165 170 175 TTC TGC AGA GAG AGT GCG CAG AAG GAT TCC GGG AGC ACA GTT CCG CCG 753 Phe Cys Arg Glu Ser Ala Gln Lys Asp Ser Gly Ser Thr Val Pro Pro 180 185 190 AGT TTG GAA AGC AGA GTG GAG AAC AAA GAG TTG ATT CCA ATG CAA CAA 801 Ser Leu Glu Ser Arg Val Glu Asn Lys Glu Leu Ile Pro Met Gln Gln 195 200 205 210 ATT TTA GAA GAA GCG GAG CCA CAG GGG CAA CTA CAA GAA GCG TTC CAG 849 Ile Leu Glu Glu Ala Glu Pro Gln Gly Gln Leu Gln Glu Ala Phe Gln 215 220 225 GGG AAG CGC CCC CTG TTT TCT AAG TGT GGC AGT ACC CAT GAG GAC AGG 897 Gly Lys Arg Pro Leu Phe Ser Lys Cys Gly Ser Thr His Glu Asp Arg 230 235 240 GTG GAA AAG CAG TCC GGA GAC CCC TTG CCC CTG AAA CTT GAA AAT TCT 945 Val Glu Lys Gln Ser Gly Asp Pro Leu Pro Leu Lys Leu Glu Asn Ser 245 250 255 CCT GAA GCA GAA GGA CTC AAC AGC ATC TCA GAT GTC AAT AAG AAT GGT 993 Pro Glu Ala Glu Gly Leu Asn Ser Ile Ser Asp Val Asn Lys Asn Gly 260 265 270 TCC ATA GAA GGG GAA GAC TCT AAA AAT AAT GAA TTG CAG AAC AGT GCC 1041 Ser Ile Glu Gly Glu Asp Ser Lys Asn Asn Glu Leu Gln Asn Ser Ala 275 280 285 290 AGG TGT TCC AAC CTT GTT CTA TGT CAG CAC ATC CCG AAA GCA GAG AGG 1089 Arg Cys Ser Asn Leu Val Leu Cys Gln His Ile Pro Lys Ala Glu Arg 295 300 305 CCC ACT GAC AGT GAG GAA CAC GGG AAC AAG TGC AAG CAA AGT TTC CAC 1137 Pro Thr Asp Ser Glu Glu His Gly Asn Lys Cys Lys Gln Ser Phe His 310 315 320 ATG GTG ACG TGG CAC GTG CTG AAA CCT CAC AAG TCT GAC AGT GGA GAC 1185 Met Val Thr Trp His Val Leu Lys Pro His Lys Ser Asp Ser Gly Asp 325 330 335 AGT TTC CAT CAT TCC AGC CTT TTT GAG ACC CAG AGG CAG CTC CAT GAA 1233 Ser Phe His His Ser Ser Leu Phe Glu Thr Gln Arg Gln Leu His Glu 340 345 350 GAA AGA CCT TAT AAA TGT GGT AAC TGT GGG AAG AGT TTC AAA CAA CGC 1281 Glu Arg Pro Tyr Lys Cys Gly Asn Cys Gly Lys Ser Phe Lys Gln Arg 355 360 365 370 TCT GAC CTC TTT AGA CAC CAG AGA ATC CAC ACA GGT GAG AAA CCC TAT 1329 Ser Asp Leu Phe Arg His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr 375 380 385 GGC TGC CAA GAA TGT GGG AAA AGC TTC AGC CAG AGT GCT GCC CTG ACC 1377 Gly Cys Gln Glu Cys Gly Lys Ser Phe Ser Gln Ser Ala Ala Leu Thr 390 395 400 AAG CAC CAG AGG ACA CAC ACA GGC GAG AAG CCG TAC ACC TGT CTG AAA 1425 Lys His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Thr Cys Leu Lys 405 410 415 TGT GGG GAG CGC TTC AGG CAG AAT TCA CAC CTA AAT CGT CAT CAA AGT 1473 Cys Gly Glu Arg Phe Arg Gln Asn Ser His Leu Asn Arg His Gln Ser 420 425 430 ACC CAC AGT AGA GAC AAA CAT TTT AAA TGT GAG GAA TGC GGG GAA ACC 1521 Thr His Ser Arg Asp Lys His Phe Lys Cys Glu Glu Cys Gly Glu Thr 435 440 445 450 TGT CAT ATT TCC AAC CTT TTT AGA CAT CAG AGA CTA CAT AAA GGG GAA 1569 Cys His Ile Ser Asn Leu Phe Arg His Gln Arg Leu His Lys Gly Glu 455 460 465 AGA CCC TAT AAG TGT GAA GAA TGC GAG AAG AGC TTC AAA CAG CGC TCT 1617 Arg Pro Tyr Lys Cys Glu Glu Cys Glu Lys Ser Phe Lys Gln Arg Ser 470 475 480 GAC CTC TTT AAA CAC CAC AGA ATC CAC ACT GGG GAG AAG CCC TAT GGA 1665 Asp Leu Phe Lys His His Arg Ile His Thr Gly Glu Lys Pro Tyr Gly 485 490 495 TGT TCC GTC TGT GGG AAA CGC TTC AAT CAG AGT GCA ACC CTC ATT AAA 1713 Cys Ser Val Cys Gly Lys Arg Phe Asn Gln Ser Ala Thr Leu Ile Lys 500 505 510 CAC CAG AGA ATT CAC ACT GGG GAA AAG CCT TAC AAA TGT CTT GAA TGT 1761 His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Leu Glu Cys 515 520 525 530 GGG GAA AGA TTT AGA CAA AGT ACA CAC CTT ATC CGA CAC CAA AGA ATT 1809 Gly Glu Arg Phe Arg Gln Ser Thr His Leu Ile Arg His Gln Arg Ile 535 540 545 CAT CAA AAT AAA GTG CTG TCG GCT GGG CGT GGT GGC TCG CGC CTG TAA 1857 His Gln Asn Lys Val Leu Ser Ala Gly Arg Gly Gly Ser Arg Leu * 550 555 560 TCCCAGCACT TTGGGAGGCC AAGGCAGGCA GATCATTTGA GATCAGGAGT TTGAAACCAG 1917 CCTGGCCAAC ATGGTAAAAT CCTGTCTTTA CTAAAAATAC AGAAATGAGC CGGGCATGGT 1977 GGTGCATGCC TGTAAGCCCA GCTATTCGGG AGGCTGAGGT AGGAGAATCA CTTGAACCCA 2037 GGAGGCGGAA GTTGCAGTGA GCTGAGATCA TGCCACTGCA CTCCAGCCTG GGCAACAGAG 2097 CGAGACTCCA TTTCAAAAAA GAAATAAAGT GCTGTCATTT TGATATGTTT CAAAAAAAAA 2157 AAAAAAAAAA A 2168SEQ ID NO: 15 Sequence length: 2168 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence characteristics: Characterizing symbol: CDS Location: 172. . 1857 method to determine the characteristics: E SEQ: CGAGAGAGTT GTAGGCGCAA AGCTGAGGAA AGGAGAGTGT GGAGAGGGGC CTGGTGTGGT 60 GGGGCCCGGT GTTTGGGACC GGAGGGTGTT GACGGCTGAT GAGTTCCTTG GGTTTGCTCT 120 TTCTTCACCT GAAAAGAAGA CTCCAGGAAG GGCAGCACAT GCCGGAGAAA G ATG AAT 177 Met Asn 1 TCC AGC TTG ACC GCC CAG AGG CGC GGC AGT GAC GCC GAG TTG GGA CCC 225 Ser Ser Leu Thr Ala Gln Arg Arg Gly Ser Asp Ala Glu Leu Gly Pro 5 10 15 TGG GTG ATG GCT GCG AGG TCC AAG GAC GCG GCG CCG TCC CAA CGC GAC 273 Trp Val Met Ala Ala Arg Ser Lys Asp Ala Ala Pro Ser Gln Arg Asp 20 25 30 GGA CTT TTG CCC GTG AAA GTG GAG GAA GAC TCA CCC GGA AGT TGG GAG 321 Gly Leu Leu Pro Val Lys Val Glu Glu Asp Ser Pro Gly Ser Trp Glu 35 40 45 50 CCC AAC TAT CCC GCG GCT TCG CCG GAC CCC GAA ACT TCT CGA CTG CAC 369 Pro Asn Tyr Pro Ala Ala Ser Pro Asp Pro Glu Thr Ser Arg Leu His 55 60 65 TTT AGG CAG CTG CGT TAC CAG GAG GTG GCT GGA CCG GAA GAG GCG CTG 417 Phe Arg Gln Leu Arg Tyr Gln Glu Val Ala Gly Pro Glu Glu Ala Leu 70 75 80 AGC CGG CTC CGA GA A CTC TGT CGT CGG TGG CTG AGA CCC GAG CTG CTC 465 Ser Arg Leu Arg Glu Leu Cys Arg Arg Trp Leu Arg Pro Glu Leu Leu 85 90 95 TCC AAG GAG CAG ATC CTG GAG CTG CTG GTG CTG GAG CAG TTC CTC ACC 513 Ser Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe Leu Thr 100 105 110 ATC CTG CCC GAG GAG CTT CAA GCC TGG GTG CGA GAG CAC TGC CCA GAG 561 Ile Leu Pro Glu Glu Leu Gln Ala Trp Val Arg Glu His Cys Pro Glu 115 120 125 130 AGC GGG GAG GAG GCG GTG GCC GTG GTG CGG GCT CTG CAG CGA GCG CTC 609 Ser Gly Glu Glu Ala Val Ala Val Val Arg Ala Leu Gln Arg Ala Leu 135 140 145 GAT GGA ACC TCA TCC CAG GGG ATG GTG ACT TTC GAG GAC ACG GCT GTG 657 Asp Gly Thr Ser Ser Gln Gly Met Val Thr Phe Glu Asp Thr Ala Val 150 155 160 TCT CTA ACC TGG GAG GAG TGG GAG CGC CTG GAC CCA GCA CGG AGG GAC 705 Ser Leu Thr Trp Glu Glu Trp Glu Arg Leu Asp Pro Ala Arg Arg Asp 165 170 175 TTC TGC AGA GAG AGT GCG CAG AAG GAT TCC GGG AGC ACA GTT CCG CCG 753 Phe Cys Arg Glu Ser Ala Gln Lys Asp Ser Gly Ser Thr Val Pro Pro 180 185 190 AGT TTG G AA AGC AGA GTG GAG AAC AAA GAG TTG ATT CCA ATG CAA CAA 801 Ser Leu Glu Ser Arg Val Glu Asn Lys Glu Leu Ile Pro Met Gln Gln 195 200 205 210 ATT TTA GAA GAA GCG GAG CCA CAG GGG CAA CTA CAA GAA GCG TTC CAG 849 Ile Leu Glu Glu Ala Glu Pro Gln Gly Gln Leu Gln Glu Ala Phe Gln 215 220 225 GGG AAG CGC CCC CTG TTT TCT AAG TGT GGC AGT ACC CAT GAG GAC AGG 897 Gly Lys Arg Pro Leu Phe Ser Lys Cys Gly Ser Thr His Glu Asp Arg 230 235 240 GTG GAA AAG CAG TCC GGA GAC CCC TTG CCC CTG AAA CTT GAA AAT TCT 945 Val Glu Lys Gln Ser Gly Asp Pro Leu Pro Leu Lys Leu Glu Asn Ser 245 250 255 CCT GAA GCA GAA GGA CTC AAC AGC ATC TCA GAT GTC AAT AAG AAT GGT 993 Pro Glu Ala Glu Gly Leu Asn Ser Ile Ser Asp Val Asn Lys Asn Gly 260 265 270 270 TCC ATA GAA GGG GAA GAC TCT AAA AAT AAT GAA TTG CAG AAC AGT GCC 1041 Ser Ile Glu Gly Glu Asp Ser Lys Asn Asn Glu Leu Gln Asn Ser Ala 275 280 285 290 AGG TGT TCC AAC CTT GTT CTA TGT CAG CAC ATC CCG AAA GCA GAG AGG 1089 Arg Cys Ser Asn Leu Val Leu Cys Gln His Ile Pro Lys Ala Glu Arg 295 300 305 CCC ACT GAC AGT GAG GAA CAC GGG AAC AAG TGC AAG CAA AGT TTC CAC 1137 Pro Thr Asp Ser Glu Glu His Gly Asn Lys Cys Lys Gln Ser Phe His 310 315 320 ATG GTG ACG TGG CAC GTG CTG AAA CCT CAC AAG TCT GAC AGT GGA GAC 1185 Met Val Thr Trp His Val Leu Lys Pro His Lys Ser Asp Ser Gly Asp 325 330 335 AGT TTC CAT CAT TCC AGC CTT TTT GAG ACC CAG AGG CAG CTC CAT GAA 1233 Ser Phe His His Ser Ser Leu Phe Glu Thr Gln Arg Gln Leu His Glu 340 345 350 GAA AGA CCT TAT AAA TGT GGT AAC TGT GGG AAG AGT TTC AAA CAA CGC 1281 Glu Arg Pro Tyr Lys Cys Gly Asn Cys Gly Lys Ser Phe Lys Gln Arg 355 360 365 370 TCT GAC CTC TTT AGA CAC CAG AGA ATC CAC ACA GGT GAG AAA CCC TAT 1329 Ser Asp Leu Phe Arg His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr 375 380 385 GGC TGC CAA GAA TGT GGG AAA AGC TTC AGC CAG AGT GCT GCC CTG ACC 1377 Gly Cys Gln Glu Cys Gly Lys Ser Phe Ser Gln Ser Ala Ala Leu Thr 390 395 400 AAG CAC CAG AGG ACA CAC ACA GGC GAG AAG CCG TAC ACC TGT CTG AAA 1425 Lys His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Thr Cys Leu Lys 405 410 415 TGT GGG GAG CGC TTC AGG CAG AAT TCA CAC CTA AAT CGT CAT CAA AGT 1473 Cys Gly Glu Arg Phe Arg Gln Asn Ser His Leu Asn Arg His Gln Ser 420 425 430 ACC CAC AGT AGA GAC AAA CAT TTT AAA TGT GAG GAA TGC GGG GAA ACC 1521 Thr His Ser Arg Asp Lys His Phe Lys Cys Glu Glu Cys Gly Glu Thr 435 440 445 450 TGT CAT ATT TCC AAC CTT TTT AGA CAT CAG AGA CTA CAT AAA GGG GAA 1569 Cys His Ile Ser Asn Leu Phe Arg His Gln Arg Leu His Lys Gly Glu 455 460 465 AGA CCC TAT AAG TGT GAA GAA TGC GAG AAG AGC TTC AAA CAG CGC TCT 1617 Arg Pro Tyr Lys Cys Glu Glu Cys Glu Lys Ser Phe Lys Gln Arg Ser 470 475 480 GAC CTC TTT AAA CAC CAC AGA ATC CAC ACT GGG GAG AAG CCC TAT GGA 1665 Asp Leu Phe Lys His His Arg Ile His Thr Gly Glu Lys Pro Tyr Gly 485 490 495 TGT TCC GTC TGT GGG AAA CGC TTC AAT CAG AGT GCA ACC CTC ATT AAA 1713 Cys Ser Val Cys Gly Lys Arg Phe Asn Gln Ser Ala Thr Leu Ile Lys 500 505 510 CAC CAG AGA ATT CAC ACT GGG GAA AAG CCT TAC AAA TGT CTT GAA TGT 1761 His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Leu Glu Cys 515 520 525 530 GGG GAA AGA TTT AGA CAA AGT ACA CAC CTT ATC CGA CAC CAA AGA ATT 1809 Gly Glu Arg Phe Arg Gln Ser Thr His Leu Ile Arg His Gln Arg Ile 535 540 545 CAT CAA AAT AAA GTG CTG TCG GCT GGG CGT GGT GGC TCG CGC CTG TAA 1857 His Gln Asn Lys Val Leu Ser Ala Gly Arg Gly Gly Ser Arg Leu * 550 555 560 TGTAAGCCCA GCTATTCGGG AGGCTGAGGT AGGAGAATCA CTTGAACCCA 2037 GGAGGCGGAA GTTGCAGTGA GCTGAGATCA TGCCACTGCA CTCCAGCCTG GGCAACAGAG 2097 CGAGACTCCA TTTCAAAAAA GAAATAAAGT GCTGTCATTT TGATATGTTT CAAAAAAAAA
【０１６８】配列番号：１６ 配列の長さ：２０１ 配列の型：アミノ酸 トポロジー：直線状 配列の種類：蛋白 配列： Met Asn Ser Ser Leu Thr Ala Gln Arg Arg Gly Ser Asp Ala Glu Leu 1 5 10 15 Gly Pro Trp Val Met Ala Ala Arg Ser Lys Asp Ala Ala Pro Ser Gln 20 25 30 Arg Asp Gly Leu Leu Pro Val Lys Val Glu Glu Asp Ser Pro Gly Ser 35 40 45 Trp Glu Pro Asn Tyr Pro Ala Ala Ser Pro Asp Pro Glu Thr Ser Arg 50 55 60 Leu His Phe Arg Gln Leu Arg Tyr Gln Glu Val Ala Gly Pro Glu Glu 65 70 75 80 Ala Leu Ser Arg Leu Arg Glu Leu Cys Arg Arg Trp Leu Arg Pro Glu 85 90 95 Leu Leu Ser Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe 100 105 110 Leu Thr Ile Leu Pro Glu Glu Leu Gln Ala Trp Val Arg Glu His Cys 115 120 125 Pro Glu Ser Gly Glu Glu Ala Val Ala Val Val Arg Ala Leu Gln Arg 130 135 140 Ala Leu Asp Gly Thr Ser Ser Gln Gly Met Val Thr Phe Glu Asp Thr 145 150 155 160 Ala Val Ser Leu Thr Trp Glu Glu Trp Glu Arg Leu Asp Pro Ala Arg 165 170 175 Arg Asp Phe Cys Arg Glu Ser Ala Gln Lys Asp Ser Gly Ser Thr Val 180 185 190 Pro Pro Ser Asp Thr Val Tyr Gly Pro 195 200 SEQ ID NO: 16 Sequence length: 201 Sequence type: amino acid Topology: Linear Sequence type: Protein Sequence: Met Asn Ser Ser Leu Thr Ala Gln Arg Arg Gly Ser Asp Ala Glu Leu 1 5 10 15 Gly Pro Trp Val Met Ala Ala Arg Ser Lys Asp Ala Ala Pro Ser Gln 20 25 30 Arg Asp Gly Leu Leu Pro Val Lys Val Glu Glu Asp Ser Pro Gly Ser 35 40 45 Trp Glu Pro Asn Tyr Pro Ala Ala Ser Pro Asp Pro Glu Thr Ser Arg 50 55 60 Leu His Phe Arg Gln Leu Arg Tyr Gln Glu Val Ala Gly Pro Glu Glu 65 70 75 80 Ala Leu Ser Arg Leu Arg Glu Leu Cys Arg Arg Trp Leu Arg Pro Glu 85 90 95 Leu Leu Ser Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe 100 105 110 Leu Thr Ile Leu Pro Glu Glu Leu Gln Ala Trp Val Arg Glu His Cys 115 120 125 Pro Glu Ser Gly Glu Glu Ala Val Ala Val Val Arg Ala Leu Gln Arg 130 135 140 Ala Leu Asp Gly Thr Ser Ser Gln Gly Met Val Thr Phe Glu Asp Thr 145 150 155 160 Ala Val Ser Leu Thr Trp Glu Glu Trp Glu Arg Leu Asp Pro Ala Arg 165 170 175 Arg Asp Phe Cy s Arg Glu Ser Ala Gln Lys Asp Ser Gly Ser Thr Val 180 185 190 Pro Pro Ser Asp Thr Val Tyr Gly Pro 195 200
【０１６９】配列番号：１７ 配列の長さ：６０３ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列： ATGAATTCCA GCTTGACCGC CCAGAGGCGC GGCAGTGACG CCGAGTTGGG ACCCTGGGTG 60 ATGGCTGCGA GGTCCAAGGA CGCGGCGCCG TCCCAACGCG ACGGACTTTT GCCCGTGAAA 120 GTGGAGGAAG ACTCACCCGG AAGTTGGGAG CCCAACTATC CCGCGGCTTC GCCGGACCCC 180 GAAACTTCTC GACTGCACTT TAGGCAGCTG CGTTACCAGG AGGTGGCTGG ACCGGAAGAG 240 GCGCTGAGCC GGCTCCGAGA ACTCTGTCGT CGGTGGCTGA GACCCGAGCT GCTCTCCAAG 300 GAGCAGATCC TGGAGCTGCT GGTGCTGGAG CAGTTCCTCA CCATCCTGCC CGAGGAGCTT 360 CAAGCCTGGG TGCGAGAGCA CTGCCCAGAG AGCGGGGAGG AGGCGGTGGC CGTGGTGCGG 420 GCTCTGCAGC GAGCGCTCGA TGGAACCTCA TCCCAGGGGA TGGTGACTTT CGAGGACACG 480 GCTGTGTCTC TAACCTGGGA GGAGTGGGAG CGCCTGGACC CAGCACGGAG GGACTTCTGC 540 AGAGAGAGTG CGCAGAAGGA TTCCGGGAGC ACAGTTCCGC CGAGTGACAC TGTTTATGGA 600 CCG 603SEQ ID NO: 17 Sequence length: 603 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence: ATGAATTCCA GCTTGACCGC CCAGAGGCGC GGCAGTGACG CCGAGTTGGG ACCCTGGGTG 60 ATGGCTGCGA GGTCCAGCGA CGCGGCCGTC ACGGACTTTT GCCCGTGAAA 120 GTGGAGGAAG ACTCACCCGG AAGTTGGGAG CCCAACTATC CCGCGGCTTC GCCGGACCCC 180 GAAACTTCTC GACTGCACTT TAGGCAGCTG CGTTACCAGG AGGTGGCTGG ACCGGAAGAG 240 GCGCTGAGCC GGCTCCGAGA ACTCTGTCGT CGGTGGCTGA GACCCGAGCT GCTCTCCAAG 300 GAGCAGATCC TGGAGCTGCT GGTGCTGGAG CAGTTCCTCA CCATCCTGCC CGAGGAGCTT 360 CAAGCCTGGG TGCGAGAGCA CTGCCCAGAG AGCGGGGAGG AGGCGGTGGC CGTGGTGCGG 420 GCTCTGCAGC GAGCGCTCGA TGGAACCTCA TCCCAGGGGA TGGTGACTTT CGAGGACACG 480 GCTGTGTCTC TAACCTGGGA GGAGTGGGAG CGCCTGGACC CAGCACGGAG GGACTTCTGC 540 AGAGAGAGTG CGCAGAAGGA TTCCGGGAGC ACAGTTCCGC CGAGTGACAC TGTTTATGGA 600 CCG 603
【０１７０】配列番号：１８ 配列の長さ：１０５１ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列の特徴： 特徴を表わす記号：CDS 存在位置：１５８．．７６０ 特徴を決定した方法：Ｅ 配列： GCGCAAAGCT GAGGAAAGGA GAGTGTGGAG AGGGGCCTGG TGTGGTGGGG CCCGGTGTTT 60 GGGACCGGAG GGTGTTGACG GCTGATGAGT TCCTTGGGTT TGCTCTTTCT TCACCTGAAA 120 AGAAGACTCC AGGAAGGGCA GCACATGCCG GAGAAAG ATG AAT TCC AGC TTG ACC 175 Met Asn Ser Ser Leu Thr 1 5 GCC CAG AGG CGC GGC AGT GAC GCC GAG TTG GGA CCC TGG GTG ATG GCT 223 Ala Gln Arg Arg Gly Ser Asp Ala Glu Leu Gly Pro Trp Val Met Ala 10 15 20 GCG AGG TCC AAG GAC GCG GCG CCG TCC CAA CGC GAC GGA CTT TTG CCC 271 Ala Arg Ser Lys Asp Ala Ala Pro Ser Gln Arg Asp Gly Leu Leu Pro 25 30 35 GTG AAA GTG GAG GAA GAC TCA CCC GGA AGT TGG GAG CCC AAC TAT CCC 319 Val Lys Val Glu Glu Asp Ser Pro Gly Ser Trp Glu Pro Asn Tyr Pro 40 45 50 GCG GCT TCG CCG GAC CCC GAA ACT TCT CGA CTG CAC TTT AGG CAG CTG 367 Ala Ala Ser Pro Asp Pro Glu Thr Ser Arg Leu His Phe Arg Gln Leu 55 60 65 70 CGT TAC CAG GAG GTG GCT GGA CCG GAA GAG GCG CTG AGC CGG CTC CGA 415 Arg Tyr Gln Glu Val Ala Gly Pro Glu Glu Ala Leu Ser Arg Leu Arg 75 80 85 GAA CTC TGT CGT CGG TGG CTG AGA CCC GAG CTG CTC TCC AAG GAG CAG 463 Glu Leu Cys Arg Arg Trp Leu Arg Pro Glu Leu Leu Ser Lys Glu Gln 90 95 100 ATC CTG GAG CTG CTG GTG CTG GAG CAG TTC CTC ACC ATC CTG CCC GAG 511 Ile Leu Glu Leu Leu Val Leu Glu Gln Phe Leu Thr Ile Leu Pro Glu 105 110 115 GAG CTT CAA GCC TGG GTG CGA GAG CAC TGC CCA GAG AGC GGG GAG GAG 559 Glu Leu Gln Ala Trp Val Arg Glu His Cys Pro Glu Ser Gly Glu Glu 120 125 130 GCG GTG GCC GTG GTG CGG GCT CTG CAG CGA GCG CTC GAT GGA ACC TCA 607 Ala Val Ala Val Val Arg Ala Leu Gln Arg Ala Leu Asp Gly Thr Ser 135 140 145 150 TCC CAG GGG ATG GTG ACT TTC GAG GAC ACG GCT GTG TCT CTA ACC TGG 655 Ser Gln Gly Met Val Thr Phe Glu Asp Thr Ala Val Ser Leu Thr Trp 155 160 165 GAG GAG TGG GAG CGC CTG GAC CCA GCA CGG AGG GAC TTC TGC AGA GAG 703 Glu Glu Trp Glu Arg Leu Asp Pro Ala Arg Arg Asp Phe Cys Arg Glu 170 175 180 AGT GCG CAG AAG GAT TCC GGG AGC ACA GTT CCG CCG AGT GAC ACT GTT 751 Ser Ala Gln Lys Asp Ser Gly Ser Thr Val Pro Pro Ser Asp Thr Val 185 190 195 TAT GGA CCG TAAGAGCTGA CCGCTGTCTG AAGGCTTGCC CACAGACCTT 800 Tyr Gly Pro 200 ACACTCAAAA GGATTCTCTA AAAAGTGAAT TCTTTGATGT TGATCAAACC ATGCCTTACG 860 CCTAATGACT TTTCCACATT CACTGCATTC ATAAGACTTT GCTCTTGTGA GAATTCGCTC 920 ATGCCCCAAA AGCAAAGATC TTTGATTGAA GGGTTTGCCA TCCTCATCAT ATCTGCCCTG 980 CTTCCACCTT GTTTGCGCAT TCTGATCTTG AATAAAGGTT AAGGTTTTGA AAAAAAAAAA 1040 AAAAAAAAAA A 1051SEQ ID NO: 18 Sequence length: 1051 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence characteristics: Characterizing symbol: CDS Location: 158. . 760 methods to determine the characteristics: E SEQ: GCGCAAAGCT GAGGAAAGGA GAGTGTGGAG AGGGGCCTGG TGTGGTGGGG CCCGGTGTTT 60 GGGACCGGAG GGTGTTGACG GCTGATGAGT TCCTTGGGTT TGCTCTTTCT TCACCTGAAA 120 AGAAGACTCC AGGAAGGGCA GCACATGCCG GAGAAAG ATG AAT TCC AGC TTG ACC 175 Met Asn Ser Ser Leu Thr 1 5 GCC CAG AGG CGC GGC AGT GAC GCC GAG TTG GGA CCC TGG GTG ATG GCT 223 Ala Gln Arg Arg Gly Ser Asp Ala Glu Leu Gly Pro Trp Val Met Ala 10 15 20 GCG AGG TCC AAG GAC GCG GCG CCG TCC CAA CGC GAC GGA CTT TTG CCC 271 Ala Arg Ser Lys Asp Ala Ala Pro Ser Gln Arg Asp Gly Leu Leu Pro 25 30 35 GTG AAA GTG GAG GAA GAC TCA CCC GGA AGT TGG GAG CCC AAC TAT CCC 319 Val Lys Val Glu Glu Asp Ser Pro Gly Ser Trp Glu Pro Asn Tyr Pro 40 45 50 GCG GCT TCG CCG GAC CCC GAA ACT TCT CGA CTG CAC TTT AGG CAG CTG 367 Ala Ala Ser Pro Asp Pro Glu Thr Ser Arg Leu His Phe Arg Gln Leu 55 60 65 70 CGT TAC CAG GAG GTG GCT GGA CCG GAA GAG GCG CTG AGC CGG CTC CGA 415 Arg Tyr Gln Glu Val Ala Gly Pro Glu Glu Ala Leu Ser Arg Leu Arg 75 80 85 G AA CTC TGT CGT CGG TGG CTG AGA CCC GAG CTG CTC TCC AAG GAG CAG 463 Glu Leu Cys Arg Arg Trp Leu Arg Pro Glu Leu Leu Ser Lys Glu Gln 90 95 100 ATC CTG GAG CTG CTG GTG CTG GAG CAG TTC CTC ACC ATC CTG CCC GAG 511 Ile Leu Glu Leu Leu Val Leu Glu Gln Phe Leu Thr Ile Leu Pro Glu 105 110 115 GAG CTT CAA GCC TGG GTG CGA GAG CAC TGC CCA GAG AGC GGG GAG GAG 559 Glu Leu Gln Ala Trp Val Arg Glu His Cys Pro Glu Ser Gly Glu Glu 120 125 130 GCG GTG GCC GTG GTG CGG GCT CTG CAG CGA GCG CTC GAT GGA ACC TCA 607 Ala Val Ala Val Val Arg Ala Leu Gln Arg Ala Leu Asp Gly Thr Ser 135 140 145 150 TCC CAG GGG ATG GTG ACT TTC GAG GAC ACG GCT GTG TCT CTA ACC TGG 655 Ser Gln Gly Met Val Thr Phe Glu Asp Thr Ala Val Ser Leu Thr Trp 155 160 165 GAG GAG TGG GAG CGC CTG GAC CCA GCA CGG AGG GAC TTC TGC AGA GAG 703 Glu Glu Trp Glu Arg Leu Asp Pro Ala Arg Arg Asp Phe Cys Arg Glu 170 175 180 AGT GCG CAG AAG GAT TCC GGG AGC ACA GTT CCG CCG AGT GAC ACT GTT 751 Ser Ala Gln Lys Asp Ser Gly Ser Thr Val Pro Pro Ser Asp Thr Val 185 190 195 TAT GGA CCG TAAGAGCTGA CCGCTGTCTG AAGGCTTGCC CACAGACCTT 800 Tyr Gly Pro 200 ACACTCAAAA GGATTCTCTA AAAAGTGAAT TCTTTGATGT TGATCAAACC ATGCCTTACG 860 CCTAATGACT TTTCCACATT CACTGCATTC ATAAGACTTT GCTCTTGTGA GAATTCGCTC 920 ATGCCCCAAA AGCAAAGATC TTTGATTGAA GGGTTTGCCA TCCTCATCAT ATCTGCCCTG 980 CTTCCACCTT GTTTGCGCAT TCTGATCTTG AATAAAGGTT AAGGTTTTGA AAAAAAAAAA 1040 AAAAAAAAAA A 1051
【０１７１】配列番号：１９ 配列の長さ：１４９ 配列の型：アミノ酸 トポロジー：直線状 配列の種類：蛋白 配列： Met Leu Pro Ala Ala Met Lys Gly Leu Gly Leu Ala Leu Leu Ala Val 1 5 10 15 Leu Leu Cys Ser Ala Pro Ala His Gly Leu Trp Cys Gln Asp Cys Thr 20 25 30 Leu Thr Thr Asn Ser Ser His Cys Thr Pro Lys Gln Cys Gln Pro Ser 35 40 45 Asp Thr Val Cys Ala Ser Val Arg Ile Thr Asp Pro Ser Ser Ser Arg 50 55 60 Lys Asp His Ser Val Asn Lys Met Cys Ala Ser Ser Cys Asp Phe Val 65 70 75 80 Lys Arg His Phe Phe Ser Asp Tyr Leu Met Gly Phe Ile Asn Ser Gly 85 90 95 Ile Leu Lys Val Asp Val Asp Cys Cys Glu Lys Asp Leu Cys Asn Gly 100 105 110 Ala Ala Gly Ala Gly His Ser Pro Gly Pro Trp Pro Gly Gly Ser Cys 115 120 125 Ser Ala Trp Gly Leu Pro Ser Ser Gly Leu Gly Pro Asp Val Ser Ser 130 135 140 Phe Pro Arg Gly Phe 145 SEQ ID NO: 19 Sequence length: 149 Sequence type: amino acid Topology: Linear Sequence type: Protein Sequence: Met Leu Pro Ala Ala Met Lys Gly Leu Gly Leu Ala Leu Leu Ala Val 1 5 10 15 Leu Leu Cys Ser Ala Pro Ala His Gly Leu Trp Cys Gln Asp Cys Thr 20 25 30 Leu Thr Thr Asn Ser Ser His Cys Thr Pro Lys Gln Cys Gln Pro Ser 35 40 45 Asp Thr Val Cys Ala Ser Val Arg Ile Thr Asp Pro Ser Ser Ser Arg 50 55 60 Lys Asp His Ser Val Asn Lys Met Cys Ala Ser Ser Cys Asp Phe Val 65 70 75 80 Lys Arg His Phe Phe Ser Asp Tyr Leu Met Gly Phe Ile Asn Ser Gly 85 90 95 Ile Leu Lys Val Asp Val Asp Cys Cys Glu Lys Asp Leu Cys Asn Gly 100 105 110 Ala Ala Gly Ala Gly His Ser Pro Gly Pro Trp Pro Gly Gly Ser Cys 115 120 125 Ser Ala Trp Gly Leu Pro Ser Ser Gly Leu Gly Pro Asp Val Ser Ser 130 135 140 Phe Pro Arg Gly Phe 145
【０１７２】配列番号：２０ 配列の長さ：４４７ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列： ATGCTGCCTG CAGCCATGAA GGGCCTCGGC CTGGCGCTGC TGGCCGTCCT GCTGTGCTCG 60 GCGCCCGCTC ATGGCCTGTG GTGCCAGGAC TGCACCCTGA CCACCAACTC CAGCCATTGC 120 ACCCCAAAGC AGTGCCAGCC GTCCGACACG GTGTGTGCCA GTGTCCGAAT CACCGATCCC 180 AGCAGCAGCA GGAAGGATCA CTCGGTGAAC AAGATGTGTG CCTCCTCCTG TGACTTCGTT 240 AAGCGACACT TTTTCTCAGA CTATCTGATG GGGTTTATTA ACTCTGGGAT CTTAAAGGTC 300 GACGTGGACT GCTGCGAGAA GGATTTGTGC AATGGGGCGG CAGGGGCAGG GCACAGCCCT 360 GGGCCCTGGC CGGGGGGCTC CTGCTCAGCC TGGGGCCTGC CCTCCTCTGG GCTGGGCCCT 420 GATGTCTCCT CCTTCCCACG GGGCTTC 447SEQ ID NO: 20 Sequence length: 447 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence: ATGCTGCCTG CAGCCATGAA GGGCCTCGGC CTGGCGCTGC TGGCCGTCCT GCTGTGCTCG 60 GCGCCCGCTC ATGGCCTGGCGTGCCAGGACGTGC CCACCAACTC CAGCCATTGC 120 ACCCCAAAGC AGTGCCAGCC GTCCGACACG GTGTGTGCCA GTGTCCGAAT CACCGATCCC 180 AGCAGCAGCA GGAAGGATCA CTCGGTGAAC AAGATGTGTG CCTCCTCCTG TGACTTCGTT 240 AAGCGACACT TTTTCTCAGA CTATCTGATG GGGTTTATTA ACTCTGGGAT CTTAAAGGTC 300 GACGTGGACT GCTGCGAGAA GGATTTGTGC AATGGGGCGG CAGGGGCAGG GCACAGCCCT 360 GGGCCCTGGC CGGGGGGCTC CTGCTCAGCC TGGGGCCTGC CCTCCTCTGG GCTGGGCCCT 420 GATGTCTCCT CCTTCCCACG GGGCTTC 447
【０１７３】配列番号：２１ 配列の長さ：９０１ 配列の型：核酸 鎖の数：一本鎖 トポロジー：直線状 配列の種類：DNA (cDNA) 配列の特徴： 特徴を表わす記号：CDS 存在位置：１４７．．５９３ 特徴を決定した方法：Ｅ 配列： ＣＧＧＡＴＴＣＣＧＧ ＴＣＣＧＣＡＧＧＡＧ ＡＣＣＧＡＡＧＧＣＡ ＣＡＧ
ＣＴＣＣＣＣＧ ＣＧＣＣＧＣＧＣＡＣ ＧＣＣＧＣＣＣＧＡＧ ６０ ＣＣＣＧＧＡＧＴＧＣ ＧＧＡＣＡＣＣＣＣＣ ＧＧＧＡＴＧＣＴＴＧ ＣＧＣ
ＣＣＣＡＧＡＧ ＧＡＣＣＣＧＣＧＣＣ ＣＣＡＡＧＣＣＣＣＣ １２０ ＧＣＧＣＣＧＣＣＣＣ ＣＡＧＧＣＣＣＡＣＣ ＣＧＧＡＧＣ ＡＴＧ ＣＴＧ
ＣＣＴ ＧＣＡ ＧＣＣ ＡＴＧ ＡＡＧ ＧＧＣ ＣＴＣ １７３ Ｍｅｔ Ｌｅｕ
Ｐｒｏ Ａｌａ Ａｌａ Ｍｅｔ Ｌｙｓ Ｇｌｙ Ｌｅｕ １
５ ＧＧＣ ＣＴＧ ＧＣＧ ＣＴＧ ＣＴＧ ＧＣＣ ＧＴＣ ＣＴＧ ＣＴＧ
ＴＧＣ ＴＣＧ ＧＣＧ ＣＣＣ ＧＣＴ ＣＡＴ ＧＧＣ ２２１ Ｇｌｙ Ｌｅｕ Ａｌａ Ｌｅｕ Ｌｅｕ Ａｌａ Ｖａｌ Ｌｅｕ Ｌｅｕ
Ｃｙｓ Ｓｅｒ Ａｌａ Ｐｒｏ Ａｌａ Ｈｉｓ Ｇｌｙ １０ １５
２０ ２５ ＣＴＧ ＴＧＧ ＴＧＣ ＣＡＧ ＧＡＣ ＴＧＣ ＡＣＣ ＣＴＧ ＡＣＣ
ＡＣＣ ＡＡＣ ＴＣＣ ＡＧＣ ＣＡＴ ＴＧＣ ＡＣＣ ２６９ Ｌｅｕ Ｔｒｐ Ｃｙｓ Ｇｌｎ Ａｓｐ Ｃｙｓ Ｔｈｒ Ｌｅｕ Ｔｈｒ
Ｔｈｒ Ａｓｎ Ｓｅｒ Ｓｅｒ Ｈｉｓ Ｃｙｓ Ｔｈｒ ３０
３５ ４０ ＣＣＡ ＡＡＧ ＣＡＧ ＴＧＣ ＣＡＧ ＣＣＧ ＴＣＣ ＧＡＣ ＡＣＧ
ＧＴＧ ＴＧＴ ＧＣＣ ＡＧＴ ＧＴＣ ＣＧＡ ＡＴＣ ３１７ Ｐｒｏ Ｌｙｓ Ｇｌｎ Ｃｙｓ Ｇｌｎ Ｐｒｏ Ｓｅｒ Ａｓｐ Ｔｈｒ
Ｖａｌ Ｃｙｓ Ａｌａ Ｓｅｒ Ｖａｌ Ａｒｇ Ｉｌｅ ４５ ５０
５５ ＡＣＣ ＧＡＴ ＣＣＣ ＡＧＣ ＡＧＣ ＡＧＣ ＡＧＧ ＡＡＧ ＧＡＴ
ＣＡＣ ＴＣＧ ＧＴＧ ＡＡＣ ＡＡＧ ＡＴＧ ＴＧＴ ３６５ Ｔｈｒ Ａｓｐ Ｐｒｏ Ｓｅｒ Ｓｅｒ Ｓｅｒ Ａｒｇ Ｌｙｓ Ａｓｐ
Ｈｉｓ Ｓｅｒ Ｖａｌ Ａｓｎ Ｌｙｓ Ｍｅｔ Ｃｙｓ ６０ ６５
７０ ＧＣＣ ＴＣＣ ＴＣＣ ＴＧＴ ＧＡＣ ＴＴＣ ＧＴＴ ＡＡＧ ＣＧＡ
ＣＡＣ ＴＴＴ ＴＴＣ ＴＣＡ ＧＡＣ ＴＡＴ ＣＴＧ ４１３ Ａｌａ Ｓｅｒ Ｓｅｒ Ｃｙｓ Ａｓｐ Ｐｈｅ Ｖａｌ Ｌｙｓ Ａｒｇ
Ｈｉｓ Ｐｈｅ Ｐｈｅ Ｓｅｒ Ａｓｐ Ｔｙｒ Ｌｅｕ ７５ ８０
８５ ＡＴＧ ＧＧＧ ＴＴＴ ＡＴＴ ＡＡＣ ＴＣＴ ＧＧＧ ＡＴＣ ＴＴＡ
ＡＡＧ ＧＴＣ ＧＡＣ ＧＴＧ ＧＡＣ ＴＧＣ ＴＧＣ ４６１ Ｍｅｔ Ｇｌｙ Ｐｈｅ Ｉｌｅ Ａｓｎ Ｓｅｒ Ｇｌｙ Ｉｌｅ Ｌｅｕ
Ｌｙｓ Ｖａｌ Ａｓｐ Ｖａｌ Ａｓｐ Ｃｙｓ Ｃｙｓ ９０ ９５
１００ １０５ ＧＡＧ ＡＡＧ ＧＡＴ ＴＴＧ ＴＧＣ ＡＡＴ ＧＧＧ ＧＣＧ ＧＣＡ
ＧＧＧ ＧＣＡ ＧＧＧ ＣＡＣ ＡＧＣ ＣＣＴ ＧＧＧ ５０９ Ｇｌｕ Ｌｙｓ Ａｓｐ Ｌｅｕ Ｃｙｓ Ａｓｎ Ｇｌｙ Ａｌａ Ａｌａ
Ｇｌｙ Ａｌａ Ｇｌｙ Ｈｉｓ Ｓｅｒ Ｐｒｏ Ｇｌｙ １１０
１１５ １２０ ＣＣＣ ＴＧＧ ＣＣＧ ＧＧＧ ＧＧＣ ＴＣＣ ＴＧＣ ＴＣＡ ＧＣＣ
ＴＧＧ ＧＧＣ ＣＴＧ ＣＣＣ ＴＣＣ ＴＣＴ ＧＧＧ ５５７ Ｐｒｏ Ｔｒｐ Ｐｒｏ Ｇｌｙ Ｇｌｙ Ｓｅｒ Ｃｙｓ Ｓｅｒ Ａｌａ
Ｔｒｐ Ｇｌｙ Ｌｅｕ Ｐｒｏ Ｓｅｒ Ｓｅｒ Ｇｌｙ １２５ １３０
１３５ ＣＴＧ ＧＧＣ ＣＣＴ ＧＡＴ ＧＴＣ ＴＣＣ ＴＣＣ ＴＴＣ ＣＣＡ
ＣＧＧ ＧＧＣ ＴＴＣ ＴＧＡＧＣＴＴＧＣＴ ６０３ Ｌｅｕ Ｇｌｙ Ｐｒｏ Ａｓｐ Ｖａｌ Ｓｅｒ Ｓｅｒ Ｐｈｅ Ｐｒｏ
Ａｒｇ Ｇｌｙ Ｐｈｅ １４０ １４５
ＣＣＣＣＴＧＡＧＣＣ ＴＧＴＧＧＣＴＧＣＣ ＣＴＣＴＣＣＣＣＡＧ ＣＣＴ
ＧＧＣＧＴＧＧ ＣＴＧＧＧＧＣＴＧＧ ＧＧＧＣＡＧＣＣＴＴ ６６３ ＧＧＣＣＣＡＧＣＴＣ ＣＧＴＧＧＣＴＧＴＧ ＧＣＣＴＧＴＧＧＣＴ ＣＴＣ
ＡＣＴＣＣＴＣ ＣＣＣＣＧＡＣＧＴＧ ＡＡＧＣＣＴＣＣＣＴ ７２３ ＧＴＣＴＣＴＣＣＧＣ ＣＡＧＣＴＣＴＧＡＧ ＴＣＣＣＡＧＧＣＡＧ ＣＴＧ
ＧＡＣＡＴＣＴ ＣＣＡＧＧＡＡＡＣＣ ＡＧＧＣＣＡＴＣＴＧ ７８３ ＧＧＣＡＧＧＡＧＧＣ ＣＴＧＧＧＧＡＴＧＡ ＧＧＧＴＧＧＧＧＧＧ ＧＧＡ
ＣＣＣＣＣＡＧ ＧＴＣＣＣＧＧＡＧＧ ＧＧＡＡＧＴＧＡＡＧ ８４３ ＣＡＡＣＡＧＣＣＣＡ ＧＣＴＧＧＡＡＧＧＧ ＣＧＴＣＴＴＣＴＧＣ ＧＧＡ
ＧＡＡＡＴＡＡ ＡＧＴＣＡＣＴＴＴＴ ＧＡＧＴＣＣＴＧ ９０１SEQ ID NO: 21 Sequence length: 901 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: DNA (cDNA) Sequence characteristics: Characterizing symbol: CDS Location: 147. . 593 Method of Characterization: E Sequence: CGGATTCCGG TCCGCAGGAG ACCGAAGGCA CAG
CTCCCCG CGCCGCGCAC GCCGCCCGAG 60 CCCGGAGTGC GGACACCCCC GGGATGCTTG CGC
CCCAGAG GACCCGCGCC CCAAGCCCCCC 120 GCGCCGCCCC CAGGCCCCACCCGGAGC ATG CTG
CCT GCA GCC ATG AAG GGC CTC 173 Met Leu
Pro Ala Ala Met Lys Gly Leu 1
5 GGC CTG GCG CTG CTG GCC GTC CTG CTG
TGC TCG GCG CCC GCT CAT GGC 221 Gly Leu Ala Leu Leu Ala Val Leu Leu
Cys Ser Ala Pro Ala His Gly 10 15
20 25 CTG TGG TGC CAG GAC TGC ACC CTG ACC
ACC AAC TCC AGC CAT TGC ACC 269 Leu Trp Cys Gln Asp Cys Thr Leu Thr
Thr Asn Ser Ser His Cys Thr 30
35 40 CCA AAG CAG TGC CAG CCG TCC GAC ACG
GTG TGT GCC AGT GTC CGA ATC 317 Pro Lys Gln Cys Gln Pro Ser Asp Thr
Val Cys Ala Ser Val Arg Ile 45 50
55 ACC GAT CCC AGC AGC AGC AGG AAG GAT
CAC TCG GTG AAC AAG ATG ATG TGT 365 Thr Asp Pro Ser Ser Ser Arg Lys Asp
His Ser Val Asn Lys Met Cys 60 65
70 GCC TCC TCC TGT GAC TTC GTT AAG CGA
CAC TTT TTC TCA GAC TAT CTG 413 Ala Ser Ser Cys Asp Phe Val Lys Arg
His Phe Phe Ser Asp Tyr Leu 75 80
85 ATG GGG TTT ATT AAC TCT GGG ATC TTA
AAG GTC GAC GTG GAC TGC TGC 461 Met Gly Phe Ile Asn Ser Gly Ile Leu
Lys Val Asp Val Asp Cys Cys 90 95
100 105 GAG AAG GAT TTG TGC AAT GGG GCG GCA
GGG GCA GGG CAC AGC CCT GGG 509 Glu Lys Asp Leu Cys Asn Gly Ala Ala
Gly Ala Gly His Ser Pro Gly 110
115 120 CCC TGG CCG GGG GGC TCC TGC TCA GCC
TGG GGC CTG CCC TCC TCT GGG 557 Pro Trp Pro Gly Gly Ser Cys Ser Ala
Trp Gly Leu Pro Ser Ser Gly 125 130
135 CTG GGC CCT GAT GTC TCC TCC TTC CCA
CGG GGC TTC TGAGCTTGCT 603 Leu Gly Pro Asp Val Ser Ser Phe Pro
Arg Gly Phe 140 145
CCCCTGAGCC TGTGGCTGCC CTCTCCCCAG CCT
GGCGTGG CTGGGGCTGG GGGCAGCCTTT 663 GGCCCAGCTCTCGTGGCTTGTG GCCTGTGGCT CTC
ACTCTCCC CCCCGACGTG AAGCCTCCCCT 723 GTCTCTCCGC CAGCTCTCGAG TCCCAGGCAG CTG
GACATCT CCAGGAAACC AGGCCATCTG 783 GGCAGGAGGC CTGGGGATGA GGGTGGGGGGGG GGA
CCCCCAG GTCCCGGAGGG GGAAGTGAAG 843 CAACAGCCCA GCTGGAAGGG CGTCTTCTGC GGA
GAAAATA AGTCACTTTTT GAGTCCTG 901
フロントページの続き (51)Int.Cl.6 識別記号 ＦＩ Ｃ１２Ｐ 21/08 Ｃ１２Ｐ 21/08 Ｃ１２Ｑ 1/68 Ｃ１２Ｑ 1/68 Ａ Ｇ０１Ｎ 33/53 Ｇ０１Ｎ 33/53 Ｄ // Ａ６１Ｋ 48/00 Ａ６１Ｋ 48/00 Ｇ０１Ｎ 33/577 Ｇ０１Ｎ 33/577 Ｂ (Ｃ１２Ｎ 15/09 ＺＮＡ Ｃ１２Ｒ 1:91） (Ｃ１２Ｎ 1/21 Ｃ１２Ｒ 1:19） (Ｃ１２Ｐ 21/02 Ｃ１２Ｒ 1:19） Continuation of the front page (51) Int.Cl. 6 Identification code FI C12P 21/08 C12P 21/08 C12Q 1/68 C12Q 1/68 A G01N 33/53 G01N 33/53 D // A61K 48/00 A61K 48 / 00 G01N 33/577 G01N 33/577 B (C12N 15/09 ZNA C12R 1:91) (C12N 1/21 C12R 1:19) (C12P 21/02 C12R 1:19)
Claims (3)
ードする塩基配列を含むことを特徴とするヒトｒａｂ７
ＧＴＰ結合類似タンパク遺伝子。1. A human rab7 comprising a base sequence encoding the amino acid sequence represented by SEQ ID NO: 1.
GTP binding analogous protein gene.
とを特徴とするヒトｒａｂ７ＧＴＰ結合類似タンパク遺
伝子。2. A human rab7 GTP binding analogous protein gene comprising the nucleotide sequence of SEQ ID NO: 2.
求項２に記載のヒトｒａｂ７ＧＴＰ結合類似タンパク遺
伝子。3. The human rab7 GTP binding analogous protein gene according to claim 2, which is a nucleotide sequence represented by SEQ ID NO: 3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9096908A JPH10286089A (en) | 1997-04-15 | 1997-04-15 | Human gene |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9096908A JPH10286089A (en) | 1997-04-15 | 1997-04-15 | Human gene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH10286089A true JPH10286089A (en) | 1998-10-27 |
Family
ID=14177471
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9096908A Pending JPH10286089A (en) | 1997-04-15 | 1997-04-15 | Human gene |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH10286089A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000059942A3 (en) * | 1999-04-02 | 2001-07-05 | Lilly Co Eli | Human obesity protein binding protrein-2 homolog and uses thereof |
| US6329169B1 (en) | 1995-09-29 | 2001-12-11 | Human Genome Sciences, Inc. | Nucleic acid molecules encoding cytostatin II |
| JP2018064554A (en) * | 1998-10-28 | 2018-04-26 | アボツト・モレキユラー・インコーポレイテツド | Cellular arrays and methods of detecting and using genetic disorder markers |
-
1997
- 1997-04-15 JP JP9096908A patent/JPH10286089A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6329169B1 (en) | 1995-09-29 | 2001-12-11 | Human Genome Sciences, Inc. | Nucleic acid molecules encoding cytostatin II |
| US6746674B2 (en) | 1995-09-29 | 2004-06-08 | Human Genome Sciences, Inc. | Cytostatin II |
| US7314722B2 (en) | 1995-09-29 | 2008-01-01 | Human Genome Sciences, Inc. | Cytostatin II antibodies and methods |
| JP2018064554A (en) * | 1998-10-28 | 2018-04-26 | アボツト・モレキユラー・インコーポレイテツド | Cellular arrays and methods of detecting and using genetic disorder markers |
| WO2000059942A3 (en) * | 1999-04-02 | 2001-07-05 | Lilly Co Eli | Human obesity protein binding protrein-2 homolog and uses thereof |
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