專利名稱：新型化合物的制作方法
技術(shù)領(lǐng)域：
本發(fā)明涉及新鑒定的化合物及編碼該多肽的多核苷酸，本發(fā)明還涉及它們在診斷中的應(yīng)用，以及它們在鑒定有潛在治療作用的激動劑和拮抗劑的化合物中的用途，本發(fā)明還涉及所述多肽和多核苷酸的制備。本發(fā)明所述的多核苷酸及多肽還涉及具有信號序列的蛋白，該信號序列可使所述蛋白分泌于胞外或者與膜相連(下文往往統(tǒng)稱為分泌蛋白或分泌多肽)。
背景技術(shù)：
由于“功能基因組”，即以基因組或基因?yàn)榛A(chǔ)的高通量生物學(xué)的出現(xiàn)，使得藥物開發(fā)方法現(xiàn)正經(jīng)歷一場重大變革。以鑒定基因或基因產(chǎn)物作治療靶標(biāo)為手段的方法迅速取代了原來以“定位克隆”為基礎(chǔ)的方法。一種表型，即一種生物功能或一種疾病被鑒定出來后，接著就根據(jù)其遺傳圖譜位置回溯到負(fù)責(zé)基因(responsible gene)。
功能基因組在很大程度上依賴于高通量DNA測序技術(shù)和各種生物信息學(xué)工具，從現(xiàn)有的多種分子生物學(xué)數(shù)據(jù)庫中鑒定出有潛在價值的基因序列。需要不斷對其他基因及其蛋白/多肽進(jìn)行鑒定和定性以作為藥物開發(fā)的靶標(biāo)。
那些天然分泌到血液、淋巴或其他體液中，或者分泌到細(xì)胞膜上的蛋白及多肽是研發(fā)藥物的首要目標(biāo)。原因在于該目標(biāo)可以相對容易地將治療蛋白靶向其作用位置(體液或細(xì)胞膜)。真核細(xì)胞和原核細(xì)胞將蛋白質(zhì)分泌入胞外區(qū)間的天然通道分別為內(nèi)質(zhì)網(wǎng)和內(nèi)膜(Palade，1975，Science，189，347；Milstein，Brownlee，Harrison，and Mathews，1972，Nature New Biol.，239，117；Blobel，and Dobberstein，1975，J.Cell.Biol.，67，835).反之，現(xiàn)在還沒有發(fā)現(xiàn)一條將蛋白質(zhì)由細(xì)胞外輸入細(xì)胞內(nèi)的天然通道(除了胞吐作用，即蛇毒液中的毒素侵入細(xì)胞的機(jī)制外)。因此，將蛋白治療物靶入細(xì)胞就面臨著巨大困難。
分泌型及膜關(guān)聯(lián)型蛋白包括但不僅限于所有肽激素及其受體(包括但不限于胰島素、生長激素、趨化因子、細(xì)胞因子、神經(jīng)肽、整聯(lián)蛋白、激肽釋放酶、核纖層蛋白、黑色素、利尿鈉激素、neuropsin，神經(jīng)營養(yǎng)蛋白，垂體激素、多效蛋白(pleiotropins)，前列腺素、分泌粒蛋白、選擇蛋白、血小板球蛋白、胸腺素)，乳腺癌及腸癌基因產(chǎn)物、苗條蛋白(leptin)、肥胖基因蛋白及其受體、血清白蛋白、過氧化物歧化酶、剪接體蛋白、7TM(跨膜蛋白)蛋白也稱為G-蛋白偶聯(lián)受體、免疫球蛋白、幾個家族的絲氨酸蛋白酶(包括但不限于血液凝固級聯(lián)反應(yīng)蛋白、消化酶)、脫氧核糖核酸酶I、等。
FDA或外國機(jī)構(gòu)承認(rèn)治療作用的分泌型或膜-關(guān)聯(lián)型蛋白包括但不限于所有肽類激素及其受體(包括但不限于胰島素、胰高血糖素、生長激素、絨毛膜促性腺素、促卵泡激素、促黃體素釋放激素(luteinizing hormone)、降鈣素、促腎上腺皮質(zhì)激素(ACTH)、血管升壓素、白細(xì)胞介素、干擾素、免疫球蛋白、乳鐵傳遞蛋白、(有多家公司銷售的不同產(chǎn)品)、組織型纖溶酶原激活物(Alteplase by Genentech)、hyaulorindase(Wydase by Wyeth-Ayerst)，α鏈球菌脫氧核糖核酸酶(Pulmozyme\by Genentech)，Chymodiactin(chymopapain by Knoll)，糖腦苷酶(Ceredase by Genzyme)，鏈激酶(Kabikinase by Pharmacia)(Streptase by Astra)等。這表明分泌型及膜-關(guān)聯(lián)型蛋白質(zhì)作為治療靶標(biāo)已有確證的歷史。顯然，需要對其他能夠預(yù)防、減緩或糾正功能紊亂或疾病的分泌型及膜關(guān)聯(lián)型蛋白質(zhì)進(jìn)行鑒定及定性，所述功能紊亂或疾病包括但不限于糖尿病、乳腺癌、前列腺癌、結(jié)腸癌及其他惡性腫瘤、高血壓及低血壓、肥胖癥、過食癥、厭食癥、生長畸形、哮喘、燥狂抑郁病、癡呆、精神狂亂、智力低下、亨廷頓氏病、圖雷特氏(Tourette)綜合征、精神分裂癥、生長發(fā)育、精神發(fā)育或性發(fā)育障礙、以及血液級聯(lián)反應(yīng)系統(tǒng)功能紊亂(包括導(dǎo)致卒中(stroke)的那些功能紊亂)。本發(fā)明中含前導(dǎo)序列的蛋白還可以用來進(jìn)一步闡明目前還未完全理解的蛋白輸送機(jī)制，因而可以用作研究工具。
發(fā)明概述本發(fā)明涉及表I中列出的基因的特定多肽及多核苷酸，包括制備其的重組材料和方法。這類多肽和多核苷酸與治療特定疾病的方法相關(guān)，所述疾病包括但不限于表III和V所列疾病，下文稱作“本發(fā)明所述疾病”。另一方面，本發(fā)明涉及用本發(fā)明提供材料鑒別激動劑和拮抗劑(例如，抑制劑)的方法，以及用鑒別出的化合物治療與表I所列基因的多肽和/或多核苷酸失衡相關(guān)的病癥的方法。另一方面，本發(fā)明還涉及用來檢測與表I所列基因活性或水平異常有關(guān)的疾病的診斷試驗(yàn)。本發(fā)明另一方面涉及多肽以及多核苷酸，所述多核苷酸包括序列表中所列的任何核苷酸序列，所述多肽包括上述多核苷酸編碼的多肽。另一方面，本發(fā)明還涉及包括序列表所列任一多肽序列的多肽及其制備所用的重組材料和方法。本發(fā)明另一方面還涉及使用所述多肽和多核苷酸的方法。所述使用包括治療因本發(fā)明所述基因的表達(dá)、產(chǎn)量、功能或代謝異常而引發(fā)的疾病、異常及紊亂(這些情況下文統(tǒng)稱疾病)，本領(lǐng)域技術(shù)人員能夠很容易地從與每個所附序列公開的其它蛋白的同源性方面理解這些疾病。另一方面，本發(fā)明涉及用本發(fā)明提供的材料鑒定激動劑和拮抗劑的方法，以及治療與鑒定出的化合物失衡相關(guān)的疾病的方法。本發(fā)明另一方面還涉及檢測與本發(fā)明所述分泌型蛋白的活性或水平異常有關(guān)的疾病的診斷試驗(yàn)。
發(fā)明描述第一方面，本發(fā)明涉及表I中所列基因的多肽。所述多肽包括(a)由包括序列表中所列序列的多核苷酸編碼的分離多肽，本發(fā)明中提到序列表中所列多核苷酸或多肽時，要參考序列表部分的序列列表；(b)一種分離多肽，該多肽包括與序列表中多肽序列具有至少95％，96％，97％，98％，或99％同一性的多肽序列；(c)一種分離多肽，該多肽包括序列表中所列的多肽序列；(d)一種分離多肽，該多肽與序列表中列出的多肽序列之間具有至少95％，96％，97％，98％，或99％的同一性；(e)序列表中列出的多肽序列；以及(f)一種分離多肽，該多肽具有或包括與序列表所列多肽序列之間的同一性指數(shù)為0.95，0.96，0.97，0.98，或0.99的多肽序列；(g)(a)～(f)中所述多肽的片段及變體。
本發(fā)明所述多肽是表II中基因家族的成員。因此根據(jù)表III和V中的理由，它們具有治療和診斷的價值。表I中基因的多肽及多核苷酸的生物學(xué)特性在本發(fā)明中稱為表I中基因的多肽及多核苷酸的“生物學(xué)活性”。優(yōu)選地，本發(fā)明所述多肽具有表I中基因的至少一種生物學(xué)活性。
本發(fā)明所述多肽還包括上述多肽的變體，其中包括所有的等位形式及剪接變體。所述多肽可以是從標(biāo)準(zhǔn)多肽通過添加、缺失及取代變化而來，這些變化可以是保守或非保守的，或其任何組合。具體優(yōu)選變體為這樣的多肽，其中，例如，以任一組合插入、取代或缺失50～30、30～20、20～10、10～5、5～3、3～2、2～1個氨基酸。
本發(fā)明所述多肽的優(yōu)選片段包括這樣的分離多肽，該分離多肽包括其中含有來自序列表所列氨基酸序列的至少30、50或100個連續(xù)氨基酸的氨基酸序列，或者這樣的分離多肽，該分離多肽包括其中含有將序列表所列氨基酸序列截短或缺失至少30、50或100個連續(xù)氨基酸的氨基酸序列。優(yōu)選片段是能介導(dǎo)表I中基因的多肽和多核苷酸的生物學(xué)活性的生物活性片段，包括那些具有近似活性或改良活性的片段，或者是不良活性降低的片段。另外優(yōu)選的片段是在動物體，尤其是人體中具有抗原性或免疫原性的片段。
可以通過肽合成技術(shù)利用本發(fā)明所述多肽片段制備本發(fā)明中相應(yīng)的全長多肽；因此，這些變體可以當(dāng)作制備本發(fā)明全長多肽的中間體。本發(fā)明中的多肽可以是“成熟”蛋白的形式，也可以是前體或融合蛋白等更大蛋白的一部分。通常，包括一段額外的氨基酸序列是有利的，其中所述氨基酸序列含有分泌或前導(dǎo)序列、前序列，有助于純化的序列，例如多組氨酸殘基，或者在重組過程中用來保持穩(wěn)定的一段額外的氨基酸序列。
本發(fā)明所述多肽可以任何適當(dāng)?shù)姆绞街苽洌缈梢苑蛛x自天然來源的材料，分離自含表達(dá)系統(tǒng)(見下文)的基因工程宿主細(xì)胞，或者化學(xué)合成，例如使用自動肽合成儀，或者上述方法的組合。制備所述肽方法為本領(lǐng)域技術(shù)人員所熟知。
另一方面，本發(fā)明涉及表I中所列基因的多肽。這些多肽包括(a)一種分離多核苷酸，其中包含與序列表中多核苷酸序列之間具有至少95％，96％，97％，98％，或99％同一性的多核苷酸序列；(b)一種分離多核苷酸，其中包含序列表中所列的多核苷酸；(c)一種分離多核苷酸，該多核苷酸與序列表中列出的多核苷酸之間具有至少95％，96％，97％，98％，或99％的同一性；(d)序列表中列出的分離多核苷酸；(e)一種分離的多核苷酸，其中包含編碼如下多肽序列的多核苷酸序列所述多肽序列與序列表中多肽序列之間具有至少95％，96％，97％，98％，或99％的同一性；(f)一種分離多核苷酸，其中包含編碼序列表中多肽的多核苷酸序列；(g)一種分離的多核苷酸，其具有如下核苷酸序列所述序列編碼的多肽與序列表中多肽序列之間具有至少95％，96％，97％，98％，或99％的同一性；(h)一種分離多核苷酸，該多核苷酸編碼序列表中的多肽；(i)一種分離多核苷酸，該多核苷酸具有或包含與序列表所列多核苷酸序列之間的同一性指數(shù)為0.95，0.96，0.97，0.98，或0.99的多核苷酸序列；(j)一種分離多核苷酸，其具有或包含編碼如下多肽序列的多核苷酸序列所述多肽序列與序列表中所列多肽序列之間的同一性指數(shù)為0.95，0.96，0.97，0.98，或0.99；以及上述多核苷酸的片段或變體，或者上述多核苷酸全長序列的互補(bǔ)多核苷酸。
本發(fā)明所述多核苷酸的優(yōu)選片段包括一段分離的多核苷酸，該分離的多核苷酸含有如下核苷酸序列所述核苷酸序列具有至少15、30、50或100個來自序列表中所列序列的連續(xù)核苷酸；或者所述分離的多核苷酸包括如下序列所述序列具有序列表中序列截短或缺失了至少30、50或100個連續(xù)核苷酸的序列。
本發(fā)明所述多核苷酸的優(yōu)選變體包括剪接變體、等位變體以及多態(tài)性變體，包括含1個或多個單個核苷酸多態(tài)性(SNPs)的多核苷酸。
本發(fā)明所述多核苷酸還包括編碼符合下述條件多肽變體的多核苷酸即所述多肽變體中包含序列表中的氨基酸序列，以及該氨基酸序列中以任一組合取代、刪除或添加了50～30、30～20、20～10、10～5、5～3、3～2、2～1或1個氨基酸殘基的多肽變體。
另一方面，本發(fā)明提供了本發(fā)明所述DNA序列的RNA轉(zhuǎn)錄物的多核苷酸。因此，本發(fā)明提供了具有下述特征的RNA多核苷酸(a)其中包括編碼序列表中多肽的DNA序列的RNA轉(zhuǎn)錄物；(b)其本身為編碼序列表中多肽的DNA序列的RNA轉(zhuǎn)錄物；(c)其中包括序列表中DNA序列的RNA轉(zhuǎn)錄物；或者(d)其本身是序列表中DNA序列的RNA轉(zhuǎn)錄物；以及與其互補(bǔ)的RNA多核苷酸。
序列表中多核苷酸序列與表II中多核苷酸序列之間具有同源性。序列表中多核苷酸序列是編碼序列表中多肽的cDNA。編碼序列表中多肽的多核苷酸序列可以與序列表中多肽編碼序列相同，或者它也可以是序列表中序列之外的序列，由于遺傳密碼的豐余性(簡并性)，這些序列也可以編碼序列表中的多肽。序列表中所列序列的多肽與表II中基因家族的其他蛋白相關(guān)，與表II中多肽之間具有同源性和/或結(jié)構(gòu)類似性。本發(fā)明所述的優(yōu)選多肽及多核苷酸期望與其他同源多肽及多核苷酸之間具有類似的生物功能/特性。另外，本發(fā)明優(yōu)選多肽及多核苷酸具有表I中所列基因的至少1種活性。
本發(fā)明所述多核苷酸可以用標(biāo)準(zhǔn)克隆及篩選技術(shù)從cDNA文庫中得到，該cDNA文庫源自表IV中組織的mRNA(參見，例如，Sambrook等，分子克隆實(shí)驗(yàn)指南，第二版，Cold Spring Harbor Laboratory Press，Cold SpringHarbor，N.Y.(1989)).
本發(fā)明所述多核苷酸還可以從天然來源獲得，例如基因組DNA文庫，或者可以用公知或商業(yè)化技術(shù)合成。
當(dāng)將本發(fā)明所述多核苷酸用于重組生產(chǎn)本發(fā)明所述多肽時，所述多核苷酸可以包括成熟多肽的編碼序列本身，或者與其他編碼序列位于同一閱讀框的成熟多肽的編碼序列，例如編碼前導(dǎo)或分泌序列、前-、原-、前原-蛋白序列、或其他融合肽部分的序列。例如，有助于融合多肽純化的標(biāo)記序列可以被編碼。在本發(fā)明該方面的特定優(yōu)選實(shí)施例中，所述標(biāo)記序列為六組氨酸肽，如pQE載體(Qiagen，Inc.)中提供，以及見Gentz等，Proc NatlAcad Sci USA(1989)86821-824一文中的描述，或者為一HA標(biāo)簽。多核苷酸也可以包括非編碼的5′及3′序列，例如轉(zhuǎn)錄、非翻譯序列，剪接及多腺苷酸信號，核糖體結(jié)合位點(diǎn)及穩(wěn)定mRNA的序列。
與序列表中多核苷酸序列相同或者具有足夠同一性的多核苷酸可以用作cDNA及基因組DNA的雜交探針，或者作為核酸擴(kuò)增反應(yīng)(例如，PCR)的引物。所述探針可以用來分離編碼本發(fā)明所述多肽的全長cDNA及基因組克隆，以及可以用來分離其他與序列表中序列間有高度序列相似性(通常至少為95％的同一性)的其他基因的cDNA及基因組克隆(包括編碼人源平行進(jìn)化同源物(paralogs)的基因以及其他物種來源的直向同源物(orthologs)及平行進(jìn)化同源物的基因)。優(yōu)選的探針及引物通常包括至少15個核苷酸，優(yōu)選地，至少30個核苷酸以及可以具有至少50個，如果不是至少100個核苷酸的話。具體優(yōu)選探針為30～50個核苷酸。具體優(yōu)選的引物為20～25個核苷酸。
編碼本發(fā)明所述多肽的多核苷酸，包括來自其他物種的同系物，可以通過包括下述步驟的方法來獲得用具有序列表中序列或其片段的標(biāo)記探針(優(yōu)選至少15個核苷酸)在嚴(yán)謹(jǐn)條件下篩選文庫，分離出含序列表中多核苷酸序列的全長cDNA及基因組克隆。所述雜交技術(shù)為本領(lǐng)域技術(shù)人員所熟知。優(yōu)選的嚴(yán)謹(jǐn)雜交條件包括42℃下在含下列成分的溶液中溫育過夜50％甲酰胺，5×SSC(150mM NaCI，15mM檸檬酸三鈉)、50mM磷酸鈉(pH7.6)，5×Denhardt′s溶液、10％葡聚糖硫酸酯、以及20mg/ml變性剪切后的鮭魚精DNA；然后在65℃下用0.1×SSC洗滌濾膜。因此，本發(fā)明還包括在嚴(yán)謹(jǐn)條件下用標(biāo)記探針篩選文庫獲得的分離多核苷酸，優(yōu)選地，該多核苷酸具有至少100個核苷酸殘基，所述探針為序列表中序列或其片段，優(yōu)選至少15個核苷酸。
本領(lǐng)域技術(shù)人員應(yīng)該理解，多數(shù)情況下，分離的cDNA序列是不完整的，因此編碼多肽的區(qū)域不會延伸至5’末端。這是反轉(zhuǎn)錄酶所造成的結(jié)果，該酶本身具有低“持續(xù)合成能力”(多聚反應(yīng)過程中該酶與模板結(jié)合的能力的一個指標(biāo))，因而在第一鏈cDNA合成過程中不能完成對mRNA模板的DNA拷貝。
現(xiàn)有數(shù)種本領(lǐng)域技術(shù)人員熟知的方法可以得到全長cDNA，或者延伸短cDNA，例如以cDNA末端快速擴(kuò)增法(RACE)為基礎(chǔ)的方法(參見，例如，F(xiàn)rohman et al.，Proc Nat Acad Sci USA 85，8998-9002，1988)。該技術(shù)近來的改進(jìn)，以Marathon(商標(biāo)名)技術(shù)(Clontech Laboratories Inc.)為代表，例如已經(jīng)大大簡化了較長cDNA的篩選。在Marathon(商標(biāo)名)技術(shù)中，cDNA由提取自選擇組織的mRNA制備而得到，并且在每個末端都連接上“銜接頭”序列。然后，結(jié)合使用基因特異性引物和銜接頭特異性寡核苷酸引物，通過核酸擴(kuò)增(PCR)來擴(kuò)增“丟失的”cDNA 5’末端。然后用“嵌套”引物重復(fù)PCR反應(yīng)，也就是說，設(shè)計在擴(kuò)增產(chǎn)物內(nèi)部退火的引物(通常一個為銜接頭特異性引物，該引物與銜接頭序列的3′端再退火，另一引物為基因特異性引物，該引物與已知基因序列的5′端再退火)。然后，用DNA測序儀分析該反應(yīng)產(chǎn)物，通過下述方法構(gòu)建全長cDNA即將產(chǎn)物與現(xiàn)有cDNA直接連接得到全長序列，或者利用新的序列信息設(shè)計5′引物進(jìn)行單獨(dú)的全長PCR擴(kuò)增。
本發(fā)明所述重組多肽可以用本領(lǐng)域技術(shù)人員熟知的方法通常從含表達(dá)系統(tǒng)的遺傳工程構(gòu)建的宿主細(xì)胞中制備得到。因此，另一方面，本發(fā)明涉及含本發(fā)明所述一個或多個多核苷酸的表達(dá)系統(tǒng)，涉及用所述表達(dá)系統(tǒng)通過遺傳工程手段構(gòu)建的宿主細(xì)胞，以及涉及用重組技術(shù)制備本發(fā)明所述多肽。還可以以用源自本發(fā)明所述DNA構(gòu)建體的RNA利用無細(xì)胞翻譯系統(tǒng)來制備所述蛋白。
就重組制備而言，可以用遺傳工程手段構(gòu)建宿主細(xì)胞以導(dǎo)入本發(fā)明所述多核苷酸的表達(dá)系統(tǒng)或者其部分。可以用多種常規(guī)實(shí)驗(yàn)指南中描述的方法將多核苷酸引入宿主細(xì)胞，例如Davis等，Basic Methods in MolecularBiology(1986)and Sambrook et al.(ibis)。將多核苷酸導(dǎo)入宿主細(xì)胞的優(yōu)選方法包括，例如，磷酸鈣轉(zhuǎn)染、DEAE-葡聚糖介導(dǎo)的轉(zhuǎn)染、轉(zhuǎn)位(transvection)、顯微注射、陽離子脂質(zhì)-介導(dǎo)的轉(zhuǎn)染、電穿孔、轉(zhuǎn)導(dǎo)、刮擦上樣(scrapeloading)、彈道導(dǎo)入(ballistic introduction)或感染。
合適宿主的代表性實(shí)例包括細(xì)菌細(xì)胞，例如鏈球菌、葡萄球菌、大腸桿菌、鏈霉菌及枯草芽孢桿菌細(xì)胞；真菌細(xì)胞，例如酵母細(xì)胞和曲霉菌細(xì)胞；昆蟲細(xì)胞例如果蠅S2和草地夜蛾Sf9細(xì)胞；動物細(xì)胞例如CHO、COS、HeLa、C127、3T3、BHK、HEK 293和Bowes黑色素瘤細(xì)胞；以及植物細(xì)胞。
大量的表達(dá)系統(tǒng)都可以使用，例如，染色體、附加體及病毒來源的系統(tǒng)，例如，源自下述的載體細(xì)菌質(zhì)粒、嗜菌體、轉(zhuǎn)座子、酵母附加體、插入元件、酵母染色體元件、病毒如桿狀病毒、乳多空病毒、如SV40、痘苗病毒、腺病毒、禽痘病毒、偽狂犬病毒及反轉(zhuǎn)錄病毒，以及來源其組合的載體，例如源自質(zhì)粒及嗜菌體遺傳元件的載體，例如粘粒及嗜菌粒。所述表達(dá)系統(tǒng)可以包含調(diào)控及實(shí)施表達(dá)的控制區(qū)。通常，任一能夠在宿主細(xì)胞中維持、增殖或表達(dá)多核苷酸以生成多肽的系統(tǒng)或載體都可以使用。合適的多核苷酸序列可以通過多種熟知及常規(guī)技術(shù)中的任一種插入到表達(dá)系統(tǒng)，所述技術(shù)例如，Sambrook et al.，(ibid)一書中描述的方法?？梢詫⒑线m的分泌信號導(dǎo)入目的多肽從而使得翻譯后的蛋白能夠分泌到內(nèi)質(zhì)網(wǎng)腔、周質(zhì)間隙或胞外環(huán)境。這些信號相對于所述多肽可以是內(nèi)源性的，也可以是異源性信號。
如果本發(fā)明所述多肽的表達(dá)是為了用于篩選實(shí)驗(yàn)，那么通常優(yōu)選在細(xì)胞表面制備所述多肽。這種情況下，可以在用于篩選實(shí)驗(yàn)前收獲細(xì)胞。如果多肽分泌入培養(yǎng)基中，那么就回收培養(yǎng)基以回收及純化多肽。如果在胞內(nèi)生成，那么在回收多肽之前必須首先裂解細(xì)胞。
可以采用本領(lǐng)域熟知的方法從重組細(xì)胞培養(yǎng)物中回收和純化本發(fā)明所述多肽，其中包括硫酸銨或乙醇沉淀、酸抽提、陰離子或陽離子交換層析、磷酸纖維素層析、疏水作用層析、親和層析、羥基磷灰石層析以及凝集素層析。最優(yōu)選地，用高效液相色譜來純化。當(dāng)多肽在胞內(nèi)合成、分離和/或純化過程中變性時，可以使用本領(lǐng)域熟知的蛋白重折疊技術(shù)重新生成活性構(gòu)象。
本發(fā)明所述多肽可以用作診斷試劑，檢測相關(guān)基因中的突變。突變形式的基因可以通過cDNA或基因組序列的序列表中的多核苷酸來鑒定，且其與功能紊亂相關(guān)。本發(fā)明將提供一診斷工具，該診斷工具可以增加，或確定，疾病或疾病易感性的診斷，這些疾病由基因的低表達(dá)、過表達(dá)或變化的時空表達(dá)引起。帶有基因突變的個體可以通過多種本領(lǐng)域熟知的技術(shù)在DNA水平上檢測。
待診斷核酸可以從受試者細(xì)胞中獲得，例如從血液、尿液、唾液、組織活檢或尸檢材料中獲得?；蚪MDNA可以直接用于檢測，或者在分析前用PCR，優(yōu)選用RT-PCR的方法進(jìn)行酶擴(kuò)增，或者用其他擴(kuò)增技術(shù)。RNA或cDNA也可以以類似的方式應(yīng)用。通過擴(kuò)增產(chǎn)物與正?；蛐拖啾却笮∩系淖兓瘉頇z測缺失或者插入。通過將擴(kuò)增DNA與標(biāo)記后的表1中基因的核苷酸序列雜交檢測點(diǎn)突變。用RNA酶消化或熔解溫度的差異從錯配的二螺旋中區(qū)分出完全匹配的序列。還可以DNA片段在有或無變性試劑存在的情況下，在凝膠中電泳遷移率的改變，或者通過直接DNA測序(參見，例如，Myers et al.，Science(1985)2301242)檢測DNA序列的差異。還可以用核酸酶保護(hù)試驗(yàn)檢測出特定位點(diǎn)上的序列變化，所述方法例如RNA酶及S1保護(hù)或者化學(xué)切割方法(見，Cotton et al.，Proc Natl Acad Sci USA(1985)854397-4401)。
可以構(gòu)建包含表I中基因的多核苷酸序列或其片段的寡核苷酸探針陣列以實(shí)施高效篩選，例如對基因突變的高效篩選。所述陣列優(yōu)選為高密度陣列或載網(wǎng)(grids)。
陣列技術(shù)的方法為本領(lǐng)域熟知，具有廣泛用途，并且可以用來發(fā)現(xiàn)分子遺傳學(xué)中的大量問題，包括基因表達(dá)、基因連鎖及基因變異性，參見，例如，M.Chee et al.，Science，274，610-613(1996)以及本發(fā)明引述的其他文獻(xiàn)。
也可以通過檢測多肽或mRNA表達(dá)的異常減少或增加來診斷或測定受試者對本發(fā)明所述疾病的易感性。多核苷酸數(shù)量的表達(dá)減少或增加可以用本領(lǐng)域熟知的任一方法在RNA水平上測量出來，所述方法例如，核酸擴(kuò)增、如PCR、RT-PCR、RNA酶保護(hù)、Northern印跡及其他雜交方法。陣列技術(shù)還可以用于測定蛋白水平，例如本發(fā)明所述多肽在來自宿主的樣本中的含量，這已為本領(lǐng)域技術(shù)人員所熟知。所述陣列方法包括放射免疫測定、競爭結(jié)合試驗(yàn)、Western印跡分析及ELISA試驗(yàn)。
因此另一方面，本發(fā)明涉及一種診斷試劑盒，其中包括(a)本發(fā)明所述多核苷酸，優(yōu)選序列表中的核苷酸序列，或者其片段或RNA轉(zhuǎn)錄本；(b)與(a)中多核苷酸互補(bǔ)的核苷酸序列；(c)本發(fā)明所述多肽，優(yōu)選序列表中的多肽或其片段；或者(d)抗本發(fā)明所述多肽的抗體，優(yōu)選抗序列表中的多肽的抗體。
可以理解的是，在任一所述試劑盒中，(a)，(b)，(c)或(d)中都包含一基本組分。該試劑盒可以用來診斷疾病或?qū)膊〉囊赘行?，具體為本發(fā)明所述疾病。
本發(fā)明所述核苷酸序列對于染色體定位研究很有價值。將序列表中序列特異性地靶向，且雜交到單個人源染色體特定位點(diǎn)上。在本發(fā)明的染色體上對相關(guān)序列作圖是這些序列和基因相關(guān)疾病間建立的重要的第一步。一旦將序列定位到確切的染色體位點(diǎn)上，就可以在染色體上該序列的物理位置與遺傳圖譜資料間建立相關(guān)關(guān)系。所述資料見于，例如，V.McKusick，Mendelian Inheritance in Man(available online through Johns HopkinsUniversity Welch Medical Library)。然后，通過連鎖分析(物理鄰接基因的共遺傳)，鑒定出已定位到同一染色體區(qū)域中的基因與疾病間的相關(guān)關(guān)系?；蚪M序列(基因片段等)的確切人染色體定位可以用放射雜交(RH)作圖方法確定(Walter，M.Spillett，D.，Thomas，P.，Weissenbach，J.，and Goodfellow，P.，(1994)一種構(gòu)建全基因組放射雜交圖譜的方法，Nature Genetics 7，22-28)。大量的RH試驗(yàn)板(panel)獲自Research Genetics(Huntsville，AL，USA)例如GeneBridge4 RH板(Hum Mol Genet 1996 Mar；5(3)339-46 A radiationhybrid map of the human genome.Gyapay G，Schmitt K，F(xiàn)izames C，Jones H，Vega-Czarny N，Spillett D，Muselet D，Proud′homme JF，Dib C，Auffray C，Morissette J，Weissenbach J，Goodfellow PN)。為了用所述試驗(yàn)板確定基因的染色體定位，使用根據(jù)RH DNA上目的基因設(shè)計的引物進(jìn)行93次PCR反應(yīng)。這些DNA中的每一個都包括保存在倉鼠背景(人/倉鼠雜交細(xì)胞系)中的隨機(jī)人基因組片段。這些PCR反應(yīng)得到93個分值，表示目的基因的PCR產(chǎn)物的存在與否。將這些分值與用已知位點(diǎn)基因組序列的PCR產(chǎn)物得到的分值進(jìn)行比較。所述比較在該網(wǎng)址上進(jìn)行，即http//www.genome.wi.mit.edu/。
本發(fā)明所述多核苷酸序列還是進(jìn)行組織表達(dá)研究的有效工具。通過檢測編碼多肽的mRNA，所述研究可以確定本發(fā)明所述多核苷酸的表達(dá)模式，這樣可以通過檢測編碼肽的mRNA為組織中所編碼的多肽的表達(dá)模式提供啟示。
所用的技術(shù)為本領(lǐng)域熟知，包括對排列在載網(wǎng)上的克隆的原位雜交技術(shù)，例如cDNA微陣列雜交(Schena et al，Science，270，467-470，1995 andShalon et al，Genome Res，6，639-645，1996)以及核酸擴(kuò)增技術(shù)如PCR。優(yōu)選方法使用Perkin Elmer公司提供的TAQMAN(商標(biāo)名)技術(shù)。這些試驗(yàn)的結(jié)果可以為器官中多肽的正常功能提供啟示。此外，mRNA的正常表達(dá)模式與同一基因的變化形式(例如，所述基因具有多肽編碼的潛在或調(diào)節(jié)性突變方面的改變)所編碼的mRNA的表達(dá)模式間的對比研究，可以為本發(fā)明所述多肽的作用提供有價值的發(fā)現(xiàn)，或者對其在疾病中的不適當(dāng)表達(dá)所起的作用提供有價值的發(fā)現(xiàn)。這些不適當(dāng)表達(dá)可以是時間、空間或單純量上的變化。
本發(fā)明另一方面還涉及抗體。本發(fā)明所述多肽或其片段，或表達(dá)它們的細(xì)胞，都可以用作制備抗體的免疫原，以制備針對本發(fā)明所述多肽的免疫特異性抗體?！懊庖咛禺愋浴币辉~是指所述抗體與本發(fā)明所述多肽間的親和力明顯大于其與現(xiàn)有技術(shù)中其他相關(guān)多肽間的親和力。
抗本發(fā)明所述多肽的抗體可以通過常規(guī)方法向動物，優(yōu)選非人動物，施用多肽或含表位片段、或細(xì)胞獲得。就制備單克隆抗體而言，任一能夠通過連續(xù)細(xì)胞系培養(yǎng)獲得抗體的技術(shù)都可以使用。實(shí)例包括雜交瘤技術(shù)(Kohler，G.and Milstein，C.，Nature(1975)256495-497)、trioma技術(shù)、人B-細(xì)胞雜交瘤技術(shù)(Kozbor et al.，Immunology Today(1983)472)以及EBV-雜交瘤技術(shù)(Cole et al.，Monoclonal Antibodies and Cancer Therapy，77-96，Alan R.Liss，Inc.，1985)。
用于制備單鏈抗體的技術(shù)，例如序列號為No.4,946,778的美國專利中描述的技術(shù)，也可以調(diào)整后用來制備抗本發(fā)明所述多肽的單鏈抗體。另外，轉(zhuǎn)基因鼠，或其他生物，包括其他哺乳動物，也可以用于表達(dá)人源抗體。
上述抗體可以用于分離或鑒定表達(dá)所述多肽的克隆，或者通過親和層析純化所述多肽?？贡景l(fā)明所述多肽的抗體也可以用來治療本發(fā)明所述疾病。
本發(fā)明所述多肽及多核苷酸還可以用作疫苗。因此，另一方面，本發(fā)明涉及一種激發(fā)哺乳動物免疫應(yīng)答的方法，該方法包括用本發(fā)明所述多肽接種哺乳動物，使所述哺乳動物足以產(chǎn)生抗體和/或T細(xì)胞免疫應(yīng)答，包括，例如，產(chǎn)細(xì)胞因子的T細(xì)胞或細(xì)胞毒性T細(xì)胞，以使所述動物抗御疾病，而無論疾病是否已在個體中存在。哺乳動物體內(nèi)的免疫應(yīng)答還可以通過這樣的方法來激發(fā)，該方法包括通過能指導(dǎo)多核苷酸表達(dá)并且能在體內(nèi)編碼所述多肽的載體運(yùn)載本發(fā)明所述多肽，誘導(dǎo)免疫應(yīng)答產(chǎn)生抗體，保護(hù)所述動物免遭本發(fā)明所述疾病。上述載體施用的一種方法是將其包裹顆?；?qū)⑵浒陬w粒中使其加速進(jìn)入目的細(xì)胞。所述核酸載體包括DNA、RNA、修飾后的核酸、或DNA/RNA雜合體。就用作疫苗而言，多肽或核酸載體通常以疫苗制劑(組合物)的形式提供。所述制劑可以進(jìn)一步包括一適當(dāng)載體。由于多肽可以在胃中消化，所以優(yōu)選通過非胃腸道途徑給藥(例如，皮下、肌內(nèi)、靜脈內(nèi)、或皮內(nèi)注射)。適于非胃腸道給藥的制劑包括含水及不含水的無菌注射液，其中可含有抗氧化劑、緩沖液、抑菌劑以及能使制劑與受體血液等張的溶質(zhì)；以及含水及不含水無菌懸液，其中可包括懸浮劑或增稠劑。所述制劑可以配制成單位劑量或多劑量包裝，例如，密封安瓿和小瓶，以及可以凍干方式保存，只需在使用前加入無菌液態(tài)載體。所述疫苗制劑還可包括佐劑系統(tǒng)用來增強(qiáng)制劑的免疫原性，例如水包油系統(tǒng)以及其他本領(lǐng)域已知系統(tǒng)。劑量要根據(jù)疫苗的比活性來確定，根據(jù)常規(guī)經(jīng)驗(yàn)也可以容易地確定。
本發(fā)明所述多肽具有1種或多種與1種或多種病理狀態(tài)有關(guān)的生物功能，所述病理狀態(tài)具體為本發(fā)明所述疾病。因此，鑒定出能夠刺激或抑制所述多肽的功能或水平的化合物是有用的。因此，另一方面，本發(fā)明提供了一種篩選能夠刺激或抑制所述多肽功能或水平的化合物的方法。上述方法能夠鑒定出可治療及預(yù)防本發(fā)明所述疾病的激動劑或拮抗劑?？蓮娜缦露喾N來源鑒定上述化合物，例如，細(xì)胞、無細(xì)胞制劑、化學(xué)文庫、化合物系列、以及天然產(chǎn)物混合物。鑒定出的激動劑或拮抗劑可以為天然或修飾后的所述多肽的底物、配體、受體、酶等(依情況而定)；其結(jié)構(gòu)或功能的模擬體(參見，Coligan et al.，Current Protocols in Immunology 1(2)Chapter 5(1991))或小分子。所述小分子優(yōu)選分子量低于2,000道爾頓，更優(yōu)選為300～1,000道爾頓，最優(yōu)選400～700道爾頓。優(yōu)選這些小分子為有機(jī)分子。
該篩選方法通過與候選化合物直接或間接連接的標(biāo)記物，可以簡便地檢測出候選化合物與多肽、與含所述多肽的細(xì)胞或細(xì)胞膜、或與其融合蛋白的結(jié)合。
替換地，所述篩選方法可以包括檢測(定性或定量)候選化合物與多肽同標(biāo)記競爭物(例如激動劑或拮抗劑)之間的競爭結(jié)合。另外，這些篩選方法可以測試候選化合物是否能引發(fā)由所述多肽被激發(fā)或被抑制所產(chǎn)生的信號，所述方法使用適于含多肽細(xì)胞的檢測系統(tǒng)。通常在存在已知激動劑的情況下測定活性抑制劑，觀察候選化合物存在時激動劑的活化效果。另外，篩選方法可以簡單地包括將候選化合物與含本發(fā)明所述多肽的溶液混合，形成一混合物，測量混合物中表I所列基因的活性，并且將表I所列基因的混合物的活性與不含候選化合物的對照混合物進(jìn)行比較。
本發(fā)明所述多肽可以用于常規(guī)低通量篩選方法以及還可用于高通量篩選(HTS)方式。所述HTS方式不僅可以使用96孔微量滴定板，還可以使用最近出現(xiàn)的384孔微量滴定板，而且還可用新出現(xiàn)的方法，例如Schullek etal，Anal Biochem.，246，20-29，(1997)一書描述的毫微孔方法。
融合蛋白，例如由Fc部分和表I中基因的多肽形成的融合蛋白，如上所述，也可用于高通量篩選試驗(yàn)，來鑒定本發(fā)明所述多肽的拮抗劑(see D.Bennett et al.，J Mol Recognition，852-58(1995)；and K.Johanson et al.，JBiol Chem，270(16)9459-9471(1995))。
本發(fā)明所述的多核苷酸、多肽及抗該多肽的抗體也可以用于篩選方法，檢測所加入的化合物對細(xì)胞中mRNA及多肽的產(chǎn)量的影響。例如，構(gòu)建ELISA試驗(yàn)，用本領(lǐng)域常規(guī)方法使用單克隆及多克隆抗體測定分泌型多肽及細(xì)胞連接型多肽的水平。用該方法能從適當(dāng)制備后的細(xì)胞或組織中篩選出可抑制或增加多肽產(chǎn)量的試劑(也分別稱為拮抗劑或激動劑)。
通過本領(lǐng)域已知的常規(guī)受體結(jié)合技術(shù)可用本發(fā)明所述多肽鑒定膜結(jié)合受體或可溶性受體。這些技術(shù)包括，但不限于，配體結(jié)合及交聯(lián)試驗(yàn)，其中所述多肽用放射性同位素(例如，碘125)標(biāo)記、化學(xué)修飾(例如，生物素化)、或融合到適于檢測或純化的肽序列上，以及與推定受體的來源物(細(xì)胞、細(xì)胞膜、細(xì)胞上清液、組織提取物、體液)孵育。其他方法包括生物物理學(xué)技術(shù)如表面胞質(zhì)基因組共振及光譜學(xué)方法。這些篩選方法還可用于鑒定能夠與多肽競爭性結(jié)合多肽受體的激動劑及拮抗劑。完成該試驗(yàn)的常規(guī)技術(shù)為本領(lǐng)域熟知。
本發(fā)明多肽的拮抗劑的實(shí)例包括抗體或者，在某些情況下，與配體緊密相關(guān)的多核苷酸或蛋白，可以是所述多肽的底物，受體，酶等，例如配體片段、底物、受體、酶的片段等；或者可與本發(fā)明多肽結(jié)合但不能激發(fā)應(yīng)答的小分子，該多肽的活性從而受到抑制。
篩選方法還涉及使用轉(zhuǎn)基因技術(shù)及表I中的基因。構(gòu)建轉(zhuǎn)基因動物的技術(shù)已很成熟。例如，可將表I中的基因通過微注射導(dǎo)入受精卵的雄性原核，通過反轉(zhuǎn)錄病毒轉(zhuǎn)移入植入前或植入后的胚胎，或者將遺傳工程修飾后的胚胎干細(xì)胞例如通過電穿孔注射入宿主胚泡。特別有用的轉(zhuǎn)基因動物是所謂的“敲入(knock-in)”動物，其中該動物基因組中的動物基因被人源的等同基因所取代。敲入轉(zhuǎn)基因動物可用于藥物探索過程，用作靶標(biāo)確認(rèn)，其中所述化合物對于人靶標(biāo)是特異性的。其他有用的轉(zhuǎn)基因動物為所謂的“敲除(knock-out)”動物，其中本發(fā)明所述多肽的且被細(xì)胞中內(nèi)源DNA序列編碼的動物直向進(jìn)化物的表達(dá)被部分或完全廢除?；蚯贸梢园邢蛱禺惣?xì)胞或組織，由于技術(shù)局限可能只發(fā)生在某些細(xì)胞或組織中，或者可以發(fā)生在全部，或基本上全部動物細(xì)胞中。轉(zhuǎn)基因動物技術(shù)還賦予一完整的動物表達(dá)-克隆系統(tǒng)，其中導(dǎo)入的基因被表達(dá)生成大量本發(fā)明所述多肽。
可用于上述方法的篩選試劑盒構(gòu)成本發(fā)明的另一方面。所述篩選試劑盒包括(a)本發(fā)明所述多肽；(b)表達(dá)本發(fā)明所述多肽的重組細(xì)胞；(c)表達(dá)本發(fā)明所述多肽的細(xì)胞膜；或者(d)抗本發(fā)明所述多肽的抗體；所述多肽優(yōu)選是序列表中所列多肽。
應(yīng)該理解的是，任一種所述試劑盒中，(a)，(b)，(c)或(d)可以包括一基本組分。
術(shù)語表提供下列定義以便更好地理解本發(fā)明中經(jīng)常出現(xiàn)的術(shù)語。
本發(fā)明中的“抗體”包括多克隆及單克隆抗體，嵌合、單鏈、及人源化抗體，以及Fab片段，包括Fab的產(chǎn)物或其他免疫球蛋白表達(dá)文庫的產(chǎn)物。
“分離的”是指通過人工改變了其天然狀態(tài)，即如果其是天然生成的，那么就將其從原初的環(huán)境中改變或移取出來，或者這兩種情況都同時發(fā)生。例如，生物活體中天然存在的多核苷酸或多肽不是“分離的”，但是從其天然狀態(tài)下的共存物中分離出來的同樣的多核苷酸或多肽就是“分離的”。本發(fā)明中使用的該術(shù)語就是這個含義。另外，通過轉(zhuǎn)化、基因操作或其他任一重組方法導(dǎo)入到生物體中的多核苷酸或多肽都是“分離的”，即使其仍存在于該生物體中，所述生物體可以是存活的或死亡后的。
“分泌蛋白的活性或者分泌多肽的活性”或者“分泌蛋白的生物活性或者分泌多肽的生物活性”是指所述分泌蛋白的代謝或生理功能，包括近似的活性或增強(qiáng)的活性或者減小了不需要的副作用的活性。另外還包括所述分泌蛋白的抗原活性及免疫原活性。
“分泌蛋白基因”是指包含了任一附著核苷酸序列的多核苷酸或其等位變體和/或其互補(bǔ)體。
“多核苷酸”通常是指任一多核糖核酸(RNA)或多脫氧核糖核酸(DNA)，可以是修飾后的或者未經(jīng)修飾的RNA或DNA?！岸嗪塑账帷卑ǎ幌抻?，單鏈及雙鏈DNA，DNA為單鏈和雙鏈區(qū)的混合體，單鏈及雙鏈RNA，以及由單鏈和雙鏈區(qū)形成的RNA混合體，包含DNA和RNA的雜合分子，所述DNA和RNA可以是單鏈或更通常為雙鏈或者單鏈及雙鏈區(qū)的混合體。此外，“多核苷酸”是指三鏈區(qū)，包含RNA或DNA或者同時包含二者。術(shù)語“多核苷酸”還包括含1個或多個修飾堿基的DNA或RNA以及為穩(wěn)定或其他原因?qū)羌苄揎椇蟮腄NAs或RNA?！靶揎棥眽A基包括，例如三苯甲基化的(tritylated)堿基以及肌苷等非常見堿基。可對DNA及RNA作多種修飾；因此“多核苷酸”包括自然界中常見的多核苷酸的化學(xué)、酶促或代謝方式修飾的形式，以及以病毒及細(xì)胞為特征的化學(xué)形式DNA及RNA。
“多核苷酸″還包括相對短的多核苷酸，通常稱為寡核苷酸。
“多肽″是指含2個或多個通過肽鍵或修飾后的肽鍵(即肽等排物(isostere))彼此相連的氨基酸的任一多肽。
短鏈“多肽″，通常稱為肽、寡肽或寡聚體，長鏈多肽，通常稱為蛋白質(zhì)。多肽可以包括除20種基因編碼氨基酸外的氨基酸。“多肽”包括經(jīng)天然加工如翻譯后加工或者經(jīng)本領(lǐng)域熟知的化學(xué)修飾技術(shù)加工后的氨基酸序列。所述修飾在基礎(chǔ)課本和更詳盡的專著以及大量研究文獻(xiàn)中都有詳細(xì)的描述。修飾可以發(fā)生在多肽的任一位置，包括肽骨架、氨基酸側(cè)鏈以及氨基和羧基末端。應(yīng)該理解的是同一類修飾可以同等程度或不同程度出現(xiàn)在特定多肽的數(shù)個位點(diǎn)。另外，特定的多肽可以包括多種類型的修飾。多肽可以是分支狀的(遍在蛋白化的結(jié)果)，可以是環(huán)形的，有或無分支。環(huán)形、分支狀及分支環(huán)形多肽可以得自翻譯后的天然加工或者可用合成方法來制備。所述修飾包括乙?；?、?；?、ADP-核糖基化、酰胺化、生物素化、共價連接黃素、共價連接亞鐵血紅素部分、共價連接核苷酸或核苷酸衍生物、共價連接脂類或脂類衍生物、共價連接磷脂酸肌醇(phosphotidylinositol)、交聯(lián)、環(huán)化、形成二硫鍵、去甲基化、生成共價交聯(lián)、生成胱氨酸、生成焦谷氨酸、甲?；ⅵ?羧化、糖基化、GPI錨定、羥基化、碘化、甲基化、豆蔻?；?、氧化、蛋白酶處理、磷酸化、異戊二烯化、外消旋化、硒代化(selenoylation)、磺化、轉(zhuǎn)運(yùn)-RNA介導(dǎo)的蛋白添加氨基酸如精氨酸化，以及遍在蛋白化(參見，例如，蛋白結(jié)構(gòu)及分子特性，2nd Ed.，T.E.Creighton，W.H.Freeman and Company，New York，1993；Wold，F(xiàn).，Post-translational ProteinModificationsPerspectives and Prospects，1-12，in Post-translational CovalentModification of Proteins，B.C.Johnson，Ed.，Academic Press，New York，1983；Seifter et al.，“Analysis for protein modifications and nonprotein cofactors″，Meth Enzymol，182，626-646，1990，and Rattan etal.，“Protein SynthesisPosttranslational Modifications and Aging″，Ann NY Acad Sci，663，48-62，1992)。
多肽序列“片段″是指比參考序列短但是基本保留了與標(biāo)準(zhǔn)多肽同樣的生物功能或活性的多肽序列。多核苷酸序列“片段″是指比序列表中所列參考序列短的多核苷酸序列。
“變體″是指這樣的多肽或多核苷酸序列，它們不同于參考多核苷酸或參考多肽，但是基本保留了參考多核苷酸或參考多肽的特性。多核苷酸的常見變體在核苷酸序列上不同于參考的多核苷酸。變體核苷酸序列的改變可能導(dǎo)致也可能不導(dǎo)致由所述參考多核苷酸編碼的多肽氨基酸序列的變化。核苷酸改變導(dǎo)致參考序列編碼的多肽中氨基酸取代、添加、缺失、融合及截短，討論見下文。多肽的常見變體在氨基酸序列上不同于參考多肽。通常，改變是有限度的從而使參考多肽的序列與變體的序列在整體上是十分近似的，并且多個區(qū)域是相同的。變體和參考多肽之間可因任一組合的1個或多個取代、插入、缺失而在氨基酸序列上不同。取代或插入的氨基酸殘基可以是也可以不是遺傳密碼子編碼的氨基酸殘基。常見的保守取代包括Gly，Ala；Val，Ile，Leu；Asp，Glu；Asn，Gln；Ser，Thr；Lys，Arg；以及Phe和Tyr。多核苷酸或多肽的變體可以是天然生成的如等位基因，或者也可以是天然生成的但不為人所知的變體。多核苷酸及多肽的非天然生成的變體可用誘變技術(shù)制備或直接合成。另外還包括的變體是具有1個或多個翻譯后修飾的多肽，例如糖基化、磷酸化、甲基化、ADP核糖基化等。實(shí)施方案包括N-末端氨基酸的甲基化、絲氨酸及蘇氨酸的磷酸化以及C-末端甘氨酸的修飾。
“等位基因″是指基因組特定座位上的2個或多個不同形式基因中的一種形式的基因。
“多態(tài)性″是指一群體內(nèi)基因組特定位置上核苷酸序列(以及編碼的多肽序列，如果相關(guān))的不同。
“單核苷酸多態(tài)性”(SNP)是指一群體內(nèi)基因組單個核苷酸位置上核苷酸的可變性。SNP可發(fā)生于基因組的一基因內(nèi)或基因間區(qū)中。SNPs可以用等位基因特異性擴(kuò)增來分析。這項操作需要至少3個引物。其中的一普通引物用來與待分析的多態(tài)性反相互補(bǔ)。該普通引物從多態(tài)性堿基起為50-1500個堿基。另外兩個(或多個)引物除了最后的3’堿基為與構(gòu)成多態(tài)性的2個(或多個)等位基因之一匹配而擺動外是相同的。然后在樣本DNA上進(jìn)行兩個(或多個)PCR反應(yīng)，每個PCR反應(yīng)都使用上述普通引物和1個等位特異性引物。
本發(fā)明中的“剪接變體”是指由這樣的RNA分子制備得到的cDNA分子，所述RNA分子最初從同一基因組的DNA序列轉(zhuǎn)錄而來，但是其經(jīng)過了可選擇性的RNA剪接?？蛇x擇性的RNA剪接發(fā)生在對初始RNA轉(zhuǎn)錄物進(jìn)行剪接時，通常是為了除去內(nèi)含子，這樣就會制備出不只1個的mRNA分子，其中的每一個都編碼不同的氨基酸序列。剪接變體一詞也指上述cDNA分子編碼的蛋白質(zhì)。
“同一性”是指通過序列對比測定出的兩個或多個多肽序列或者是兩個或多個多核苷酸序列之間的關(guān)系。通常，同一性是指在所比較的序列長度內(nèi)兩多肽序列之間氨基酸與氨基酸的精確對應(yīng)，或兩多核苷酸序列之間核苷酸與核苷酸的精確對應(yīng)。
“％同一性”-對于不完全對應(yīng)的序列，可以測定“％同一性”。通常，為得到序列間最大相關(guān)程度要將待比較的兩序列對齊。這其中包括為提高對齊程度在其中的1個序列插入或者在兩個序列中都插入“間隙”?？梢栽谒刃蛄腥L范圍內(nèi)測定％同一性(稱為整體對齊)，這特別適用于長度相等或非常近似的序列，或者也可以在較短的確定長度的序列的范圍內(nèi)測定(稱為局部對齊)，這更適用于不等長序列。
“相似性”是對兩多肽序列間相關(guān)程度作進(jìn)一步更精確的測量。通常，“相似性”意指兩多肽鏈的氨基酸間的對比，是在殘基逐一對比水平上的對比，不僅將確切對應(yīng)的計算在內(nèi)(如同一性的計算)，而且還要把所比序列中不確切對應(yīng)的計算在內(nèi)。在進(jìn)化的基礎(chǔ)上，一殘基可能要取代另一殘基。這種可能性有一相關(guān)“分值”，然后從中測算出兩序列間的“％相似性”。
比較兩或多序列間同一性及相似性的方法為本領(lǐng)域所熟知。因此例如，Wisconsin Sequence Analysis Package，version 9.1(Devereux J et al，NucleicAcids Res，12，387-395，1984，available from Genetics Computer Group，Madison，Wisconsin，USA)中的程序，例如程序BESTFIT和GAP，可用來測定兩核苷酸序列間的％同一性以及兩多肽序列間的％同一性和％相似性。BESTFIT使用Smith和Waterman的“局部同源性″算法(J Mol Biol，147，195-197，1981，Advances in Applied Mathematics，2，482-489，1981)，找出兩序列間最相似的單個區(qū)域。BESTFIT更適于比較長度上不近似的兩多核苷酸或兩多肽序列，該程序?qū)⑤^短序列假定為較長序列的一部分。比較過程中，GAP將兩序列對齊，根據(jù)Neddleman和Wunsch的算法(J Mol Biol，48，443-453，1970)，找出“最大相似性”。GAP更適于比較近似等長的序列，在全長序列上對齊。優(yōu)選地，每個程序中使用的參數(shù)“間隙權(quán)值″和“長度權(quán)值″對于多核苷酸序列分別為50和3，對于多肽序列則分別為12和4。優(yōu)選地，在將待比的兩序列最佳對齊時測定％同一性和相似性。
用于測定序列間同一性和/或相似性的其他程序也為本領(lǐng)域所已知，例如BLAST程序家族(Altschul S F et al，J Mol Biol，215，403-410，1990，Altschul S F et al，Nucleic Acids Res.，25389-3402，1997，available from theNational Center for Biotechnology Information(NCBD，Bethesda，Maryland，USA and accessible through the home page of the NCBI at www.ncbi.nlm.nih.gov)和FASTA(Pearson W R，Methods in Enzymology，183，63-99，1990；Pearson W R and Lipman D J，Proc Nat Acad Sci USA，85，2444-2448，1988，available as part of the Wisconsin Sequence Analysis Package)。
優(yōu)選地，使用BLOSUM62氨基酸取代矩陣(Henikoff S and HenikoffJ G，Proc.Nat.Acad Sci.USA，89，10915-10919，1992)進(jìn)行多肽序列對比，其中包括在對比前首先將核苷酸序列翻譯為氨基酸序列。
優(yōu)選地，使用BESTFIT程序測定多核苷酸或多肽查詢序列與多核苷酸或多肽標(biāo)準(zhǔn)序列之間的％同一性，其中將所述查詢序列與所述標(biāo)準(zhǔn)序列最大限度地對齊，并將程序的參數(shù)值設(shè)為缺省值。
“同一性指數(shù)”是指序列相關(guān)程度的測量，其可用來比較候選序列(多核苷酸或多肽)和標(biāo)準(zhǔn)序列。因此，例如，與標(biāo)準(zhǔn)多核苷酸序列之間的同一性指數(shù)為0.95的候選多核苷酸序列可認(rèn)為與標(biāo)準(zhǔn)序列是相同的，候選多核苷酸序列內(nèi)平均每100個核苷酸中有5個與標(biāo)準(zhǔn)序列不同。所述差異選自至少1個核苷酸缺失、取代、包括轉(zhuǎn)換和顛換、或插入。這些差異可出現(xiàn)在標(biāo)準(zhǔn)序列5′或3′末端或者兩末端之間的任一位置，可以單個核苷酸的形式散布在標(biāo)準(zhǔn)序列的核苷酸中或者也可以1個或多個連續(xù)核苷酸成組的方式出現(xiàn)在標(biāo)準(zhǔn)序列內(nèi)。換句話說，為了得到一與標(biāo)準(zhǔn)序列間同一性指數(shù)為0.95的多核苷酸序列，可以對標(biāo)準(zhǔn)序列的核苷酸平均每100個中的5個缺失、替換或插入，或其任一組合，如上文所述。必要時同樣可采用其他同一性指數(shù)，例如0.96，0.97，0.98和0.99。
類似地，就多肽而言，與標(biāo)準(zhǔn)多肽序列之間的同一性指數(shù)為0.95的候選多肽序列可認(rèn)為與標(biāo)準(zhǔn)序列是相同的，候選多肽序列內(nèi)平均每100個氨基酸中有5個與標(biāo)準(zhǔn)序列不同。所述差異選自至少1個氨基酸缺失、取代、包括保守和非保守、或插入。這些差異可出現(xiàn)在標(biāo)準(zhǔn)序列的氨基或羧基末端或者兩末端之間的任一位置，可以單個氨基酸的形式散布在標(biāo)準(zhǔn)序列的氨基酸中或者也可以1個或多個連續(xù)氨基酸成組的方式出現(xiàn)在標(biāo)準(zhǔn)序列內(nèi)。換句話說，為了得到一與標(biāo)準(zhǔn)序列間同一性指數(shù)為0.95的多肽序列，可以對標(biāo)準(zhǔn)序列的氨基酸平均每100個中的5個缺失、取代或插入，或其任一組合，如上文所述。必要時同樣采用其他同一性指數(shù)，例如0.96，0.97，0.98和0.99。
特定數(shù)目核苷酸或氨基酸差異間的相關(guān)程度及同一性指數(shù)可以表述為na≤Xa-(xa·I)。
其中，na為核苷酸或氨基酸差異的數(shù)目，xa為序列表中所列序列的核苷酸或氨基酸的總數(shù)，I為同一性指數(shù)，·為乘法運(yùn)算符，以及其中當(dāng)xa和I的乘積非整數(shù)時要將其下舍為最接近的整數(shù)，然后再被xa減。
“同系物″是本領(lǐng)域的一廣義詞匯，意指一與標(biāo)準(zhǔn)序列間有很高序列相關(guān)程度的多核苷酸或多肽序列。所述的相關(guān)程度可通過上述的測定同一性和/或相似性的方法對相關(guān)程度定量。屬于這一廣義詞匯的有“直向進(jìn)化物″及“平行進(jìn)化物″?！爸毕蜻M(jìn)化物″是指另一物種中與所述多核苷酸或多肽功能等價的多核苷酸或多肽。“平行進(jìn)化物″是指屬于功能類似的同一物種中的多核苷酸或多肽。
“融合蛋白″是指由兩個，通常為互不相關(guān)的兩個，融合基因或其片段編碼的蛋白質(zhì)。在一個實(shí)施例中，EP-A-0 464 533-A公開了包括免疫球蛋白分子恒定區(qū)的不同部分和另一種人蛋白質(zhì)或其部分的融合蛋白質(zhì)。多數(shù)情況下，用免疫球蛋白Fc區(qū)域作為融合蛋白質(zhì)的一部分有助于用于治療和診斷，可以提高藥物動力學(xué)特性[參見，例如，EP-A 0232 262]。另一方面，在某些用途時，在融合蛋白表達(dá)、檢測及純化后，需將Fc部分去掉。
所有出版物及參考文獻(xiàn)，包括但不限于該說明書中引用的專利和專利申請，作為一個整體在此引入作為參考，如同每一單篇出版物或參考文獻(xiàn)專門單獨(dú)地引入作為參考。本申請請求優(yōu)先權(quán)的任一專利申請也被完整引入作為參考，方式同上述出版物及參考文獻(xiàn)。
表1
表II
表III
(表III續(xù))
表IV.用SybrMan檢測的組織特異性mRNA的定量表達(dá)用SYBR-Green定量PCR(Applied Biosystems，F(xiàn)oster City，CA；seeSchmittgen T.D.et al.，Analytical Biochemistry 285194-204，2000)以及從各種人組織中制備的人cDNA測定基因的組織特異性mRNA的定量表達(dá)模式。使用序列表中的第一個核酸序列為每個基因設(shè)計基因特異性PCR引物。結(jié)果表示為每種組織1ng mRNA庫中檢測到的每一特定基因的mRNA的拷貝數(shù)。對每一組織RNA都進(jìn)行兩次mRNA平行測量。
表VI(續(xù))
表V.其他以特異性組織中mRNA表達(dá)為基礎(chǔ)的疾病
序列表<110>史密斯克萊恩比徹姆公司(SMITHKLINE BEECHAM CORPORATION)<120>新型化合物<130>GP50025<140>TO BE ASSIGNED<141>2001-04-26<150>60/199,963<151>2000-04-27<150>60/203,336<151>2000-05-11<150>60/207,087<151>2000-05-25<150>60/207,546<151>2000-05-26<160>78<170>FastSEQ for Windows Version 3.0<210>1<211>831<212>DNA<213>人(Homo sapiens)<400>1atgcgtggcc ttgttatggc tcccctgctc attctcctgg ttggtgggac tgaagccttt 60cgtatctgtg ccttcaatgc ccacagactg acactggcca agctaaccaa ggagtcagtg120atggatacct tagttcagat cctagcccga tgtgatatca tggtgcttca ggaggtagta180gattcttccc agaatactgt cccctttctg cttcaaaaac ttaaaagttc caggagttac240agcttcctaa acagctcatt gctggggcgc agcacataca aggaaaagta tgtgtatatc300tacaggtctg acaagacaca ggtcctaaat ttctaccaat acaacgacac agatgatatt360tttgcccgag aaccatttgt ggcccatttc actctcccta gcaaaactct tccaagtgtg420gtgctggttc ctctccacac cactcccaag gatgttgaga aggagctgaa tgccctctat480gatgtgtttc tggatgtcta ccagcgctgg cagaatgaga atgtgattct gcttggagac540ttcaatgcag actgtgcatc gctgacaaaa aaacgtctga aaagcctgct actccggact600aaggcaggct tccactgggt gattcctgat ggggaggata ctacagtgcg ggccagtact660aactgtacct atgaccgaat tgtggtgcat ggacagggct gccaaatgct gctgaaggct720gcagctacct ttgactttcc caagaggttt cagctgactg aggaagaggc tctccgcatc780agtgaccatt atcctgtaga agtggaactg agccaggcca ctccactgag t 831<210>2<211>1443<212>DNA<213>人(Homo sapiens)<400>2atgctaggcc gatttcaacc cttctccttg gtccggagtt tcagactggg atttggagcc 60tgctgctatc caaaccaaaa atgtgctact cagaccatca gaccccctga ctccaggtgc120ctagtccaag cagtttctca gaactttaat tttgcaaagg atgtgttgga tcagtggtcc180cagctggaaa aggacggact cagagggcct taccccgccc tctggaaggt tagtgccaaa240ggagaagagg acaaatggag ctttgaaagg atgactcaac tctccaagaa ggccgccagc 300atcctctcag acacctgtgc ccttagccat ggagaccggc tgatgataat cttgccccca 360acacctgaag cctactggat ctgcctggcc tgtgtgcgct tgggaatcac ctttgtgcct 420gggagccccc agctgactgc caagaaaatt cgctatcaat tacgcatgtc taaggcccag 480tgcattgtgg ctaatgaagc tatggcccca gttgtaaact ctgccgtgtc cgactgcccc 540accttgaaaa ccaagctcct ggtgtcagat aagagctatg atgggtggtt ggatttcaag 600aagttgattc aagttgcccc tccaaagcag acctacatga ggaccaaaag ccaagatcca 660atggccatat tcttcaccaa gggtacaaca ggagctccca aaatggtcga gtattcccag 720tatggtttgg gaatgggatt cagccaggct tccagacggt ggatggatct ccagccaaca 780gatgtcttgt ggagtctggg tgatgccttt ggtggatctt tatccctgag cgctgtcttg 840ggaacttggt tccaaggagc ctgtgtgttt ctgtgtcaca tgccaacctt ctgccctgag 900actgttctaa atgtcctgtc cagatttccc atcaccactc tatctgcaaa tccagagatg 960taccaggaac tgcttcagca caagtgtttc accagctaca gattcaagag tctgaagcag1020tgtgtggctg caggaggacc catcagccct ggggtgattg aggactggaa acgcatcact1080aagttggaca tctatgaagg ctatgggcag acggaaactg gtctactctg tgccacttcc1140aaaacaataa aattgaagcc aagctctctg gggaagccat tgccacctta tattgtccag1200attgtggatg aaaactcaaa tctcctgcct ccaggggaag aaggaaatat tgcaatccgc1260ataaaactaa accaacctgc ttctctgtac tgtccacaca tggtgagctg ggaggaatat1320gcttcagcaa gaggccacat gctttacctc acaggtgaca gagggatcat ggatgaagac1380ggctacttct ggtggtctgg tagagttgat gatgttgcca atgcattggg tcagagattg1440tga 1443<210>3<211>1752<212>DNA<213>人(Homo sapiens)<400>3atgctaggcc gatttcaacc cttctccttg gtccggagtt tcagactggg atttggagcc 60tgctgctatc caaaccaaaa atgtgctact cagaccatca gaccccctga ctccaggtgc120ctagtccaag cagtttctca gaactttaat tttgcaaagg atgtgttgga tcagtggtcc180cagctggaaa aggacggact cagagggcct taccccgccc tctggaaggt tagtgccaaa240ggagaagagg acaaatggag ctttgaaagg atgactcaac tctccaagaa ggccgccagc300atcctctcag acacctgtgc ccttagccat ggagaccggc tgatgataat cttgccccca360acacctgaag cctactggat ctgcctggcc tgtgtgcgct tgggaatcac ctttgtgcct420gggagccccc agctgactgc caagaaaatt cgctatcaat tacgcatgtc taaggcccag480tgcattgtgg ctaatgaagc tatggcccca gttgtaaact ctgccgtgtc cgactgcccc540accttgaaaa ccaagctcct ggtgtcagat aagagctatg atgggtggtt ggatttcaag600aagttgattc aagttgcccc tccaaagcag acctacatga ggaccaaaag ccaagatcca660atggccatat tcttcaccaa gggtacaaca ggagctccca aaatggtcga gtattcccag720tatggtttgg gaatgggatt cagccaggct tccagacggt ggatggatct ccagccaaca780gatgtcttgt ggagtctggg tgatgccttt ggtggatctt tatccctgag cgctgtcttg840ggaacttggt tccaaggagc ctgtgtgttt ctgtgtcaca tgccaacctt ctgccctgag900actgttctaa atgtcctgtc cagatttccc atcaccactc tatctgcaaa tccagagatg960taccaggaac tgcttcagca caagtgtttc accagctaca gattcaagag tctgaagcag 1020tgtgtggctg caggaggacc catcagccct ggggtgattg aggactggaa acgcatcact 1080aagttggaca tctatgaagg ctatgggcag acggaaactg gtctactctg tgccacttcc 1140aaaacaataa aattgaagcc aagctctctg gggaagccat tgccacctta tattgtccag 1200attgtggatg aaaactcaaa tctcctgcct ccaggggaag aaggaaatat tgcaatccgc 1260ataaaactaa accaacctgc ttctctgtac tgtccacaca tggtgagctg ggaggaatat 1320gcttcagcaa gaggccacat gctttacctc acaggtgaca gagggatcat ggatgaagac 1380ggctacttct ggtggtctgg tagagttgat gatgttgcca atgcattggg tcagagattt 1440tctcgccccg gggcggcggc ggcggcaagt gcggtgggag cgccgcctgg aggctggcac 1500tcattatgtg cctctgttcc cattctgcag gtggtgaagc cccctaatgt cctgactcca 1560cagttcctgt cccatgacca gggccagctc accaaagagc tacagcagca cataaagtca 1620gtgacaggcc catgcaagta ccaaaggaag gtggagtttg tcccagagct gccaaaaacc 1680gtcactggca agattaaacg ggaacttcaa gtttggtcag atgtagtcag cagtgaactc 1740agaaatgact ga 1752
<210>4<211>1746<212>DNA<213>人(Homo sapiens)<400>4atgccactga agcattatct ccttttgctg gtgggctgcc aagcctgggg tgcagggttg 60gcctaccatg gctgccctag cgagtgtacc tgctccaggg cctcccaggt ggagtgcacc 120ggggcacgca ttgtggcggt gcccacccct ctgccctgga acgccatgag cctgcagatc 180ctcaacacgc acatcactga actcaatgag tccccgttcc tcaatatttc agccctcatc 240gccctgagga ttgagaagaa tgagctgtcg cgcatcacgc ctggggcctt ccgaaacctg 300ggctcgctgc gctatctcag cctcgccaac aacaagctgc aggttctgcc catcggcctc 360ttccagggcc tggacagcct tgagtctctc cttctgtcca gtaaccagct gttgcagatc 420cagccggccc acttctccca gtgcagcaac ctcaaggagc tgcagttgca cggcaaccac 480ctggaataca tccctgacgg agccttcgac cacctggtag gactcacgaa gctcaatctg 540ggcaagaata gcctcaccca catctcaccc agggtcttcc agcacctggg caatctccag 600gtcctccggc tgtatgagaa caggctcacg gatatcccca tgggcacttt tgatgggctt 660gttaacctgc aggaactggc tctacagcag aaccagattg gactgctctc ccctggtctc 720ttccacaaca accacaacct ccagagactc tacctgtcca acaaccacat ctcccagctg 780ccacccagca tcttcatgca gctgccccag ctcaaccgtc ttactctctt tgggaattcc 840ctgaaggagc tctctctggg gatcttcggg cccatgccca acctgcggga gctttggctc 900tatgacaacc acatctcttc tctacccgac aatgtcttca gcaacctccg ccagttgcag 960gtcctgattc ttagccgcaa tcagatcagc ttcatctccc cgggtgcctt caacgggcta1020acggagcttc gggagctgtc cctccacacc aacgcactgc aggacctgga cgggaatgtc1080ttccgcatgt tggccaacct gcagaacatc tccctgcaga acaatcgcct cagacagctc1140ccagggaata tcttcgccaa cgtcaatggc ctcatggcca tccagctgca gaacaaccag1200ctggagaact tgcccctcgg catcttcgat cacctgggga aactgtgtga gctgcggctg1260tatgacaatc cctggaggtg tgactcagac atccttccgc tccgcaactg gctcctgctc1320aaccagccta ggttagggac ggacactgta cctgtgtgtt tcagcccagc caatgtccga1380ggccagtccc tcattatcat caatgtcaac gttgctgttc caagcgtcca tgtacctgag1440gtgcctagtt acccagaaac accatggtac ccagacacac ccagttaccc tgacaccaca1500tccgtctctt ctaccactga gctaaccagc cctgtggaag actacactga tctgactacc1560attcaggtca ctgatgaccg cagcgtttgg ggcatgaccc atgcccatag cgggctggcc1620attgccgcca ttgtaattgg cattgtcgcc ctggcctgct ccctggctgc ctgcgtcggc1680tgttgctgct gcaagaagag gagccaagct gtcctgatgc agatgaaggc acccaatgag1740tgttaa 1746<210>5<211>1887<212>DNA<213>人(Homo sapiens)<400>5atgcccggtg ctccagactg gagccttaat tcctccagaa atgcacgcag cctggagggg 60ctgcctctgt gtccgtggtg ggctctcttc gtcccgagag cagctgcgct ggttggactt 120caaaggaagc aggaaaacag ctcagatatc ttctttagct ctcctttcac ggtgacccca 180gacgccctac caacagccat tacatgggag cacattccgt ttgcaaagct ggcgggtcta 240attgcagggc ctttggtgga gatgtgcagg cagaggctaa gcaaagagtt tgaggccttg 300aaaggggaat tcagggacct cgggcactgt cttccaggag cccagcgagg gaacagaatc 360actaaacgaa acaagtgcgg tcagagccgt caggcgctca tcggccagag acaggaagat 420gcaggctccg ctcctctgca gatgcacccc agtgtcgctg cgctgggggc aggagctgcg 480ctgcgggaga ttcagcccct gcaaagggaa ccagagctgt catcagggcc caggaacagc 540cggctcctgt gctggggcag ccctgccacc tggaacccca cgtacctgtc ccgtgtccta 600gggcagcagg tggccgtgac tgtgacagag gctggtctcc aggctgtgcc ctggggaccc 660agcagagaat ttaatgccaa gggctctagc tcagcgagca ttagagtggg acagccccag 720aagcttaggc tcagagtcca gaggtccagg agacagtgtc cccctgtcca gtcctcacag780gacctcccac caggcggctc ccaggatggt gacttgaagg aacccacaga gagggtcact 840cgggacttat ccagtggggc cccgaggggc cgcaacctgc cagcgcctga ccagcctcaa 900cccccgctgc agaggggaac ccgtctgcgg ctccgccagc gccgtcgccg tctgctcatc 960aagaaaatgc cagctgcggc gaccatcccg gccaacagct cggacgcgcc cttcatccgg1020ccgggacccg ggacgctgga tggccgctgg gtcagcctgc accggagcca gcaggagcgc1080aagcgggtga tgcaggaggc ctgcgccaag taccgggcga gcagcagccg ccgggccgtc1140acgccccgcc acgtgtcccg tatcttcgtg gaggaccgcc accgcgtgct ctactgcgag1200gtgcccaagg ccggctgctc caattggaag cgggtgctca tggtgctggc cggcctggcc1260tcgtccactg ccgacatcca gcacaacacc gtccactatg gcagcgctct caagcgcctg1320gacaccttcg accgccaggg tatcttgcac cgtctcagca cctacaccaa gatgctcttt1380gtccgcgagc ccttcgagag gctggtgtcc gccttccgcg acaagtttga gcaccccaac1440agctactatc acccggtctt cggcaaggcc atcctggccc ggtaccgcgc caatgcctct1500cgggaggccc tgcggaccgg ctctggggtg cgttttcccg agttcgtcca gtacctgctg1560gacgtgcacc ggcccgtggg gatggacatt cactgggacc atgtcagccg gctctgcagc1620ccctgcctca tcgactacga tttcgtaggc aagttcgaga gcatggagga cgatgccaac1680ttcttcctga gcctcatccg cgcgccgcgg aacctgacct tcccccggtt caaggaccgg1740cactcgcagg aggcgcggac cacagcgagg atcgcccacc agtacttcgc ccaactctcg1800gccctgcaaa ggcagcgcac ctacgacttc tactacatgg attacctgat gttcaactat1860tccaagccct ttgcagatct gtactga1887<210>6<211>1275<212>DNA<213>人(Homo sapiens)<400>6atgaccctgc gacctggaac aatgcggctg gcctgcatgt tctcttccat cctgctgttc 60ggagctgcag gcctcctcct cttcatcagc ctgcaggacc ctacggagct cgccccccag 120caggtgccag gaataaagtt caacatcagg ccaaggcagc cccaccacga cctcccacca 180ggcggctccc aggatggtga cttgaaggaa cccacagaga gggtcactcg ggacttatcc 240agtggggccc cgaggggccg caacctgcca gcgcctgacc agcctcaacc cccgctgcag 300aggggaaccc gtctgcggct ccgccagcgc cgtcgccgtc tgctcatcaa gaaaatgcca 360gctgcggcga ccatcccggc caacagctcg gacgcgccct tcatccggcc gggacccggg 420acgctggatg gccgctgggt cagcctgcac cggagccagc aggagcgcaa gcgggtgatg 480caggaggcct gcgccaagta ccgggcgagc agcagccgcc gggccgtcac gccccgccac 540gtgtcccgta tcttcgtgga ggaccgccac cgcgtgctct actgcgaggt gcccaaggcc 600ggctgctcca attggaagcg ggtgctcatg gtgctggccg gcctggcctc gtccactgcc 660gacatccagc acaacaccgt ccactatggc agcgctctca agcgcctgga caccttcgac 720cgccagggta tcttgcaccg tctcagcacc tacaccaaga tgctctttgt ccgcgagccc 780ttcgagaggc tggtgtccgc cttccgcgac aagtttgagc accccaacag ctactatcac 840ccggtcttcg gcaaggccat cctggcccgg taccgcgcca atgcctctcg ggaggccctg 900cggaccggct ctggggtgcg ttttcccgag ttcgtccagt acctgctgga cgtgcaccgg 960cccgtgggga tggacattca ctgggaccat gtcagccggc tctgcagccc ctgcctcatc1020gactacgatt tcgtaggcaa gttcgagagc atggaggacg atgccaactt cttcctgagc1080ctcatccgcg cgccgcggaa cctgaccttc ccccggttca aggaccggca ctcgcaggag1140gcgcggacca cagcgaggat cgcccaccag tacttcgccc aactctcggc cctgcaaagg1200cagcgcacct acgacttcta ctacatggat tacctgatgt tcaactattc caagcccttt1260gcagatctgt actga 1275<210>7<211>1917<212>DNA<213>人(Homo sapiens)<400>7atggcaggag gctcagccac gacctggggt taccctgtgg ccctgctact gctggttgcc 60accctggggc tgggtaggtg gctccagccc gaccctggcc tcccaggcct ccggcacagc 120tacgactgtg ggatcaaggg aatgcagctg ctggtgttcc ccaggccagg ccagactctc 180cgcttcaagg tggtggatga atttgggaac cgatttgatg tcaacaactg ctccatctgc 240taccactggg tcacctccag gccgcaggag cctgcagtct tctcggccga ttacagaggc 300tgccacgtgc tggagaagga tgggcgtttc cacctgaggg tgttcatgga ggctgtgctg 360cccaatggtc gtgtggatgt ggcacaagac gctactctga tctgtcccaa acctgacccc 420tcccggactc tggactccca gctggcacca cccgccatgt tctctgtctc aaccccacaa 480accctttcct tcctccccac ctctggccat acctcccaag gctctggcca tgcctttccc 540agcccactgg acccagggca cagctctgtc cacccaaccc ctgctttacc atcccctgga 600cctggaccta ccctcgccac cctggctcaa ccccactggg gcaccttgga acactgggat 660gtgaacaaac gagattacat aggtacccac ctgagccagg agcagtgcca ggtggcctca 720gggcacctcc cctgcatcgt gagaagaact tcaaaagaag cctgtcagca ggctggctgc 780tgctatgaca acaccagaga ggttccctgt tactatggca acacagctac tgtccagtgc 840ttcagagatg gctacttcgt cctcgtagtg tcccaagaaa tggccttgac acacaggatc 900acactggcca acatccacct ggcctatgcc cccaccagct gctccccaac acagcacacg 960gaagctttcg tggtcttcta cttccctctc acccactgtg gaaccacaat gcaggtggct1020ggcgaccagc tcatctatga gaactggctg gtgtctggca tccacatcca aaaggggcca1080cagggttcca tcacgcggga cagcaccttc cagcttcatg tgcgctgtgt cttcaacgcc1140agtgacttcc tgcccattca ggcatccatt ttcccacccc catcgcctgc tcctatgacc1200cagcccggcc ccctgcggct tgagctgcgg attgccaaag acgagacctt cagctcgtac1260tatggggagg atgactatcc catcgtgagg ctgctccgag aaccagtcca tgtggaggtc1320cggcttctgc agaggacaga ccccaacctg gtcctgctgc tgcaccagtg ctggggcgct1380cccagtgcca accccttcca gcagccccag tggcccatcc tgtcagacgg atgccctttc1440aagggcgaca gctacagaac ccaaatggta gccttggacg gggccacacc tttccagtcg1500cactaccagc gattcactgt tgctaccttc gccctcctgg actcaggctc ccagagagcc1560ctcagaggac tggtttactt gttctgcagc acctctgcct gccacacctc agggctggag1620acttgctcca ctgcatgtag cactggcact acaagacagc gacgatcctc aggtcaccgt1680aatgacactg ccaggcccca ggacatcgtg agctctccgg ggccagtggg ctttgaggat1740tcttatgggc aggagcccac acttgggccc acagactcca atgggaactc cagcctgaga1800cctctccttt gggcggtcct tttgctgcca gctgttgccc tggtccttgg gtttggtgtc1860tttgtgggcc tgagccagac ctgggcccag aagctctggg aaagcaacag acagtga 1917<210>8<211>687<212>DNA<213>人(Homo sapiens)<400>8atgaaacctc ttgctcagct tctcctcttt ctcctccagt ttcagaaagg gaatctagtt 60tcacaaagca gctcaacccc attgatggtg aatggggttc tgggggagtc agtaactctt 120cccctggagt ttcctgcagg agagaggatc cagttcatca cttggctttg caatggaaca 180tcttttgcct tcctagaacc ctatgaaggc aaaagtccaa aaatctacgt gactcatccg 240aaatggcaaa agcgactgag cttcacccag tcctactccc cgcagctcag caacctggag 300atggaaaaca taggctttta cagtgcccag atagccacag agacctctgc aaagctgtcc 360agttacactc tgaggatatt caagcagctg ccaaggcctc aagttagagt ggattctatc 420atctctgaaa atgggatctg taatgccatc ttgaggtgtt ctgtggagga aggaggagag 480accatcacat atgagtggac atcaatggga ccaggggctg ctgtgtccca cgtgggcctt 540catgacctgg attggatcta cacttgcaca gctctgaatc ctgttagcta cagcaactct 600actcttaccc ttgctgcaca gctttgtgca agtaagagtc cccttctggt ctctctagca 660ccccttggaa atgttttgtc tggtctc 687<210>9<211>933<212>DNA<213>人(Homo sapiens)<400>9atgaaacctc ttgctcagct tctcctcttt ctcctccagt ttcagaaagg gaatctagtt 60tcacaaagca gctcaacccc attgatggtg aatggggttc tgggggagtc agtaactctt 120cccctggagt ttcctgcagg agagaggatc cagttcatca cttggctttg caatggaaca 180tcttttgcct tcctagaacc ctatgaaggc aaaagtccaa aaatctacgt gactcatccg 240aaatggcaaa agcgactgag cttcacccag tcctactccc cgcagctcag caacctggag 300atggaaaaca taggctttta cagtgcccag atagccacag agacctctgc aaagctgtcc 360agttacactc tgaggatatt caagcagctg ccaaggcctc aagttagagt ggattctatc 420atctctgaaa atgggatctg taatgccatc ttgaggtgtt ctgtggagga aggaggagag 480accatcacat atgagtggac atcaatggga ccaggggctg ctgtgtccca cgtgggcctt 540catgacctgg attggatcta cacttgcaca gctctgaatc ctgttagcta cagcaactct 600actcttaccc ttgctgcaca gctttgtgca agttccaagg cagctgaagg cacctattgc 660ccagtgaaat ggattttcct ggggaacagg cttcttctcc ttgtgttcct tggtgtccta 720cgaacttggc atattcaggc acaggtgctc agcaaaccct tgaggcctaa ctcaggggaa 780cttgtgaatc tttcctcaat cccataccct tgggaaccat ctcacacagc tgatgccact 840tggcttggga agtggggtgg aagtgagggg gagagaaaga gcacgtggaa tataagcacc 900acgaaaagac actggaaaag cttctataaa taa 933<210>10<211>2526<212>DNA<213>人(Homo sapiens)<400>10atgaagctgt ggattcatct cttttattca tctctccttg cctgtatatc tttacactcc 60caaactccag tgctctcatc cagaggctct tgtgattctc tttgcaattg tgaggaaaaa 120gatggcacaa tgctaataaa ttgtgaagca aaaggtatca agatggtatc tgaaataagt 180gtgccaccat cacgaccttt ccaactaagc ttattaaata acggcttgac gatgcttcac 240acaaatgact tttctgggct taccaatgct atttcaatac accttggatt taacaatatt 300gcagatattg agataggtgc atttaatggc cttggcctcc tgaaacaact tcatatcaat 360cacaattctt tagaaattct taaagaggat actttccatg gactggaaaa cctggaattc 420ctgcaagcag ataacaattt tatcacagtg attgaaccaa gtgcctttag caagctcaac 480agactcaaag tgttaatttt aaatgacaat gctattgaga gtcttcctcc aaacatcttc 540cgatttgttc ctttaaccca tctagatctt cgtggaaatc aattacaaac attgccttat 600gttggttttc tcgaacacat tggccgaata ttggatcttc agttggagga caacaaatgg 660gcctgcaatt gtgacttatt gcagttaaaa acttggttgg agaacatgcc tccacagtct 720ataattggtg atgttgtctg caacagccct ccatttttta aaggaagtat actcagtaga 780ctaaagaagg aatctatttg ccctactcca ccagtgtatg aagaacatga ggatccttca 840ggatcattac atctggcagc aacatcttca ataaatgata gtcgcatgtc aactaagacc 900acgtccattc taaaactacc caccaaagca ccaggtttga taccttatat tacaaagcca 960tccactcaac ttccaggacc ttactgccct attccttgta actgcaaagt cctatcccca1020tcaggacttc taatacattg tcaggagcgc aacattgaaa gcttatcaga tctgagacct1080cctccgcaaa atcctagaaa gctcattcta gcgggaaata ttattcacag tttaatgaag1140tctgatctag tggaatattt cactttggaa atgcttcact tgggaaacaa tcgtattgaa1200gttcttgaag aaggatcgtt tatgaaccta acgagattac aaaaactcta tctaaatggt1260aaccacctga ccaaattaag taaaggcatg ttccttggtc tccataatct tgaatactta1320tatcttgaat acaatgccat taaggaaata ctgccaggaa cctttaatcc aatgcctaaa1380cttaaagtcc tgtatttaaa taacaacctc ctccaagttt taccaccaca tattttttca1440ggggttcctc taactaaggt aaatcttaaa acaaaccagt ttacccatct acctgtaagt1500aatattttgg atgatcttga tttactaacc cagattgacc ttgaggataa cccctgggac1560tgctcctgtg acctggttgg actgcagcaa tggatacaaa agttaagcaa gaacacagtg1620acagatgaca tcctctgcac ttcccccggg catctcgaca aaaaggaatt gaaagcccta1680aatagtgaaa ttctctgtcc aggtttagta aataacccat ccatgccaac acagactagt1740taccttatgg tcaccactcc tgcaacaaca acaaatacgg ctgatactat tttacgatct1800cttacggacg ctgtgccact gtctgttcta atattgggac ttctgattat gttcatcact1860attgttttct gtgctgcagg gatagtggtt cttgttcttc accgcaggag aagatacaaa1920aagaaacaag tagatgagca aatgagagac aacagtcctg tgcatcttca gtacagcatg1980tatggccata aaaccactca tcacactact gaaagaccct ctgcctcact ctatgaacag2040cacatggtga gccccatggt tcatgtctat agaagtccat cctttggtcc aaagcatctg2100gaagaggaag aagagaggaa tgagaaagaa ggaagtgatg caaaacatct ccaaagaagt2160cttttggaac aggaaaatca ttcaccactc acagggtcaa atatgaaata caaaaccacg2220aaccaatcaa cagaattttt atccttccaa gatgccagct cattgtacag aaacatttta2280gaaaaagaaa gggaacttca gcaactggga atcacagaat acctaaggaa aaacattgct2340cagctccagc ctgatatgga ggcacattat cctggagccc acgaagagct gaagttaatg2400gaaacattaa tgtactcacg tccaaggaag gtattagtgg aacagacaaa aaatgagtat2460tttgaactta aagctaattt acatgctgaa cctgactatt tagaagtcct ggagcagcaa2520acatag 2526
<210>11<211>726<212>DNA<213>人(Homo sapiens)<400>11atgggaaacc ctggcctggc ctggctggtg ctgctgggct tggtgctgct tctgagctct 60ttcatggaga gaggaggcca cagtcccagc cctgctgccc tgtcggccat ggaaaaccta 120atcacctatg ctgtccagaa gggccacctg tcatccagtt atgttcagcc acttcttgtg 180aaaggcgaga actgcctggc ccctcggcag aagacaagcc tgaagaaggc ttgccccggc 240gttgtcccac ggtctgtgtg gggagccagg gagacccact gtcccaggat gactctccca 300gcgaagtatg gcatcattat ccacactgcc gggaggacct gcaacatttc tgatgagtgc 360cgcctgctgg tccgggacat ccagtctttc tacatagaca ggctcaagtc atgcgacatt 420ggttataact tcctggtggg ccaggatggc gccatttatg aaggggtggg ctggaatgtc 480caaggctcct ccacccctgg ctacgatgac attgccctgg gcattacctt catgggcacc 540ttcacaggta taccacccaa tgctgcagca ctagaggcag cccaagacct gatccagtgt 600gccatggtca aagggtacct gactcccaac tacctgctgg tgggccacag tgatgtggcc 660cgaaccttgt ctcctgggca ggctttgtac aacatcatca gcacctggcc tcatttcaaa 720cactga726<210>12<211>1110<212>DNA<213>人(Homo sapiens)<400>12atgctgccgt ggcttcttgt cttctctgct ctgggtctcc aggcctgggg tgattcctcc 60tggaacaaaa cacaagctaa acaggtatca gaggggctcc agtacctatt tgagaacatc 120tcccagctca ctgaaaaaga tgtctccacc acggtctctc gcaaggcatg gggggcagaa 180gctgttggct gcagtattca gctgaccacg ccagtgaatg tccttgttat acaccatgtc 240cctggactgg agtgtcacga ccggacagtc tgcagccaga gactgcggga actgcaggcc 300catcatgtcc acaacaacag tgggtgtgat gtggcctaca acttcctggt tggggatgat 360ggcagggtgt atgaaggtgt tggctggaat atccaaggag tgcacaccca aggctacaac 420aacatctccc tgggctttgc cttcttcggc actaagaaag gccacagtcc cagccctgct 480gccctgtcgg ccatggaaaa cctaatcacc tatgctgtcc agaagggcca cctgtcatcc 540agttatgttc agccacttct tgtgaaaggc gagaactgcc tggcccctcg gcagaagaca 600agcctgaaga aggcttgccc cggcgttgtc ccacggtctg tgtggggagc cagggagacc 660cactgtccca ggatgactct cccagcgaag tatggcatca ttatccacac tgccgggagg 720acctgcaaca tttctgatga gtgccgcctg ctggtccggg acatccagtc tttctacata 780gacaggctca agtcatgcga cattggttat aacttcctgg tgggccagga tggcgccatt 840tatgaagggg tgggctggaa tgtccaaggc tcctccaccc ctggctacga tgacattgcc 900ctgggcatta ccttcatggg caccttcaca ggtataccac ccaatgctgc agcactagag 960gcagcccaag acctgatcca gtgtgccatg gtcaaagggt acctgactcc caactacctg1020ctggtgggcc acagtgatgt ggcccgaacc ttgtctcctg ggcaggcttt gtacaacatc1080atcagcacct ggcctcattt caaacactga 1110<210>13<211>1149<212>DNA<213>人(Homo sapiens)<400>13atggccccgc gcgcgggaca gccggggctc caggggctgc tgctcgtggc ggcggcgctg 60agccagcccg cggcaccctg ccccttccag tgctactgct tcggcggccc caagctgctg 120ctgcgctgcg cgtcgggagc cgagctccgc cagcctccgc gggacgtgcc gcccgacgcg 180cgcaacctca ccatcgtagg cgccaacctg acggtgctgc gcgcggccgc cttcgccggc 240ggggacgggg acggcgacca ggcggcgggc gtgcgcctgc cgctcctgag cgcgctgcgc 300ctcacgcaca accacatcga ggtggtggag gacggcgcct tcgacgggct gcccagcctg 360gcggcgctcg acctcagcca caacccgctg cgcgccctgg gcggcggcgc cttccgcggg 420ctgcccgcgc tgcgctcgct gcagctcaac cacgcgctgg tgcgcggcgg ccccgcgctg 480ctggccgcgc tggacgctgc gctggcaccg ctggccgagc ttcgcctgct gggcctagcg 540ggcaacgcgc tgagccgtct gccgccagcc gccctgcgcc tggcgcgcct ggagcagctg 600gacgtgcgcc tcaacgcgct ggccggcctg gaccccgacg agctgcgcgc gctggagcgc 660gatggcggcc tccccgggcc gcgcctgctg ctcgccgaca accccctgcg ctgcggctgt 720gccgcacgcc ccctgctggc ctggctgcgc aacgccacgg agcgcgtgcc cgactcgcgg 780cgcctgcgct gcgccgcccc gcgggcgctg ctagaccggc cgctactgga cctggacggg 840gcgcggcttc gctgcgcgga cagcggcgcc gacgctcgcg gagaggaggc ggaggccgcc 900ggcccggagc tggaagcctc ctacgtgttc ttcgggctgg tgctggcact catcggcctc 960atcttcctca tggtgctcta cctaaaccgc cgcggcatcc agcgctggat gcgcaacctg1020cgcgaggcgt gccgggacca gatggagggc taccactacc gctacgagca ggacgccgac1080ccgcgccgcg cgcccgcgcc cgccgcgccc gcgggctccc gcgccacctc cccgggctcg1140gggctctga1149<210>14<211>558<212>DNA<213>人(Homo sapiens)<400>14atgatgctgc tgttgctgtg tctggggttg accctcgtct gtgcccagga ggaagaaaac 60aatgatgctg tgacaagcaa cttcgatctg tcaaagattt caggagagtg gtattcggtt 120ctcttggcct ctgactgcag ggaaaagata gaagaagatg gaagcatgag ggtttttgtc 180aaacacattg attacctggg gaattcttct ctgactttta aattgcatga aatagaaaat 240ggaaactgta ctgaaattaa tttggcttgt aaaccaacag aaaagaatgc catatgtagt 300actgactata acggacttaa tgtcattgac atacttgaaa cggactatga taattatata 360tatttttata acaagaatat caagaatggg gaaacattcc taatgctgga gctctatgtt 420cgaacaccgg atgtgagctc acaactcaag gagaggtttg tgaaatattg tgaagaacat 480gggattgata aggaaaacat atttgacttg accaaagttg atcgctgtct ccaggcccga 540gatgagggag cagcctag 558<210>15<211>1761<212>DNA<213>人(Homo sapiens)<400>15atgcattaca accttcaggg tcccacgaga agaatcagaa tttctttgtt aaacgatgga 60ggactcaaaa tagccaatgt gactaaagct gatgctggaa cttacacctg catggcagaa 120aaccagtttg ggaaagcaaa tggcacaaca catttggttg ttacggaacc aacaagaata 180actttggcac catctaacat ggatgtttct gttggtgaaa gcgtcatatt gccctgccag 240gtacaacatg acccgctgtt agacatcatc tttacctggt atttcaatgg ggcccttgca 300gattttaaga aagatggatc tcactttgag aaagttggtg ggagttcatc tggtgattta 360atgatcagaa acattcagct gaaacacagt gggaaatatg tttgtatggt gcaaacgggg 420gtggacagtg tttcatctgc tgctgacctc atagtaagag gttcacctgg accaccagaa 480aatgtgaagg tagatgaaat tacagacaca acagcccaac tctcttggaa agaaggtaaa 540gacaaccata gcccagttat atcctattct atccaggctc ggacaccttt ctccgtgggt 600tggcaaaccg tcacaacagt gcctgaggtc atcgatggga agacgcacac agccactgta 660gttgagttaa acccatgggt ggaatatgaa tttcgggttg tagccagtaa caaaattgga 720ggtggagaac caagtttacc ctcagaaaaa gtaagaactg aagaggcagt tccagaagtg 780cctccttctg aagtcaatgg aggaggcgga agccggtctg aacttgtgat aacctgggat 840ccagtccctg aagaactaca gaatggtgaa ggttttgggt atgttgttgc tttccgccct 900cttggggtta ccacctggat ccagacagtg gtgacatccc ctgacacccc aagatatgtc 960tttaggaatg aaagcatcgt gccatattca ccatatgaag ttaaagtggg tgtttataat1020aacaaaggtg aaggaccatt tagcccagtg acaacagtgt tctctgcaga agaagagcct1080acagtggccc catctcaagt ctctgcaaat agcctatctt cctcagaaat tgaggtttca1140tggaacacca ttccttggaa gttgagcaat ggacatttac tgggctatga ggtgcggtac1200tggaatgggg gtggaaagga ggaatcatcc agtaagatga aagtggcagg aaatgagaca1260tcagccagac tacggggcct gaagagcaac ctggcctatt acacggctgt ccgggcttac1320aacagtgccg gcgctgggcc ttttagcgcc acagttaatg taaccaccaa gaaaacgcct1380cccagtcagc caccaggaaa tgttgtttgg aatgccacag acactaaagt gttacttaat1440tgggagcaag ttaaagccat ggagaatgag tcagaagtaa caggatataa agttttctat1500aggactagca gtcaaaataa cgtacaagta ctgaacacaa ataaaacttc agctgaactt1560gtgctgccca ttaaagagga ctacattatt gaagtcaagg ccacaacaga tggaggggat1620gggaccagta gtgaacagat caggattcca cgaataacca gtatggatgc aagaggatcc1680acttcagcca tctcgaatgt ccaccctatg tcaagttata tgcctatagt actgttctta1740attgtatatg tcctgtggtg a 1761<210>16<211>3081<212>DNA<213>人(Homo sapiens)<400>16atgctggtgg tggaaagagt aatggttctt cccattgggt tcccccttgg tgtgagtgat 60gattccacac tgcatggccc gatttttatt caagaaccaa gtcctgtaat gttccctttg 120gattctgagg agaaaaaagt gaagctcaat tgtgaagtta aaggaaatcc aaaacctcat 180atcaggtgga agttaaatgg aacagatgtt gacactggta tggatttccg ctacagtgtt 240gttgaaggga gcttgttgat caataacccc aataaaaccc aagatgctgg aacgtaccag 300tgcacagcga caaactcgtt tggaacaatt gttagcagag aagcaaagct tcagtttgct 360tatcttgaca actttaaaac aagaacaaga agcactgtgt ctgtccgtcg aggtcaagga 420atggtgctac tgtgtggccc gccaccccat tctggagagc tgagttatgc ctggatcttc 480aatgaatacc cttcctatca ggataatcgc cgctttgttt ctcaagagac tgggaatctg 540tatattgcca aagtagaaaa atcagatgtt gggaattata cctgtgtggt taccaatacc 600gtgacaaacc acaaggtcct ggggccacct acaccactaa tattgagaaa tgatggagtg 660atgggtgaat atgagcccaa aatagaagtg cagttcccag aaacagttcc gactgcaaaa 720ggagcaacgg tgaagctgga atgctttgct ttaggaaatc cagtaccaac tattatctgg 780cgaagagctg atggaaagcc aatagcaagg aaagccagaa gacacaagtc aaatggaatt 840cttgagatcc ctaattttca gcaggaggat gctggtttat atgaatgtgt agctgaaaat 900tccagaggga aaaatgtagc aaggggacag ctaactttct atgctcaacc taattggatt 960caaaaaataa atgatattca cgtggccatg gaagaaaatg tcttttggga atgtaaagca1020aatggaaggc ctaagcctac atacaagtgg ctaaaaaatg gcgaacctct gctaactcgg1080gatagaattc aaattgagca aggaacactc aacataacaa tagtgaacct ctcagatgct1140ggcatgtatc agtgtttggc agagaataaa catggagtta tcttttccaa cgcagagctt1200agtgttatag ctgtaggtcc agatttttca agaacactct tgaaaagagt aactcttgtc1260aaagtgggag gtgaagttgt cattgagtgt aagccaaaag cgtctccaaa acctgtttac1320acctggaaga aaggaaggga tatattaaaa gaaaatgaaa gaattaccat ttctgaagat1380ggaaacctca gaatcatcaa cgttactaaa tcagacgctg ggagttatac ctgtatagcc1440actaaccatt ttggaactgc tagcagtact ggaaacttgg tagtgaaaga tccaacaagg1500gtaatggtac ccccttccag tatggatgtc actgttggag agagtattgt tttaccgtgc1560caggtaacgc atgatcactc gctagacatc gtgtttactt ggtcatttaa tggacacctg1620atagactttg acagagatgg ggaccacttt gaaagagttg gaggggattc agctggtgat1680ttgatgatcc gaaacatcca actgaagcat gctgggaaat atgtctgcat ggtccaaaca1740agtgtggaca ggctatctgc tgctgcagac ctgattgtaa gaggtcctcc aggtccccca1800gaggctgtga caatagacga aatcacagat accactgctc agctctcctg gagacccggg1860cctgacaacc acagccccat caccatgtat gtcattcaag ccaggactcc attctccgtg1920ggctggcaag cagtcagtac agtcccagaa ctcattgatg ggaagacatt cacagcgacc1980gtggtgggtt tgaacccttg ggttgaatat gaattccgca cagttgcagc caacgtgatt2040gggattgggg agcccagccg cccctcagag aaacggagaa cagaagaagc tctccccgaa2100gtcacaccag cgaatgtcag tggtggcgga ggcagcaaat ctgaactggt tataacctgg2160gagacggtcc ctgaggaatt acagaatggt cgaggctttg gttatgtggt ggccttccgg2220ccctacggta aaatgatctg gatgctgaca gtgctggcct cagctgatgc ctctagatac2280gtgttcagga atgagagcgt gcaccccttc tctccctttg aggttaaagt aggtgtcttc2340aacaacaaag gagaaggccc tttcagtccc accacggtgg tgtattctgc agaagaagaa2400cccaccaaac caccagccag tatctttgcc agaagtcttt ctgccacaga tattgaagtt2460ttctgggcct ccccactgga gaagaataga ggacgaatac aaggttatga ggttaaatat2520tggagacatg aagacaaaga agaaaatgct agaaaaatac gaacagttgg aaatcagaca2580tcaacaaaaa tcacgaactt aaaaggcagt gtgctgtatc acttagctgt caaggcatat2640aattctgctg ggacaggccc ctctagtgca acagtcaatg tgacaacccg aaagccacca2700ccaagtcaac cccccggaaa catcatatgg aattcatcag actccaaaat tatcctgaat2760tgggatcaag tgaaggccct ggataatgag tcggaagtaa aaggatacaa agtcttgtac2820agatggaaca gacaaagcag cacatctgtc attgaaacaa ataaaacatc ggtggagctt2880tctttgcctt tcgatgaaga ttatataata gaaattaagc cattcagcga cggaggagat2940ggcagcagca gtgaacaaat tcgaattcca aagatatcaa atgcctacgc gagaggatct3000ggggcttcca cttcgaatgc atgtacgctg tcagccatca gtacaataat gatttccctc3060acagctaggt ccagtttatg a 3081<210>17<211>2535<212>DNA<213>人(Homo sapiens)<400>17atggacaacc cacaggctct gccactcttc ctactcctgg cctccttggt agggatcctc 60accctcagag cctcttctgg acttcagcaa accaacttct cctctgcctt ctcttcagac 120tcaaagagct cttcccaggg gctgggtgtg gaagttccct ccatcaaacc tcccagctgg 180aaagttccag atcagttcct ggattcaaaa gcctctgctg gaatctctga ttccagctgg 240tttcctgagg ccctgagttc caacatgtct gggtccttct ggtcaaatgt ttctgctgag 300ggccaagatt tgagcccggt ttcccccttc tctgaaaccc ctggttctga agtatttcct 360gatatttcgg atcctcaagt tcctgccaaa gaccccaagc cttccttcac tgttaagacc 420ccagcttcaa acatttctac tcaagtctcc cataccaaac tgtctgttga ggccccagat 480tcaaaattct ccccggatga tatggatctt aaactctctg cccagagccc tgaatccaaa 540ttttctgcag agacccactc agctgcaagc tttccccagc aggtgggggg cccactcgct 600gtgctggtgg ggaccaccat ccggctcccc ctagtcccaa tccccaaccc tgggcccccc 660acctctctgg tggtctggcg ccggggctca aaggtgctgg cagctggggg cctggggcca 720ggggcacctc tgatcagcct ggaccctgct caccgagacc acctgcgatt tgaccaggcc 780cggggggttc tggagctcgc ctctgcccag ctggacgatg caggggtcta cacggctgag 840gtcatccggg caggggtctc ccagcagact cacgagttca cggtgggtgt gtatgagccc 900ctaccccagc tgtcggttca gcccaaggct ccagagacag aggagggggc ggccgagctc 960cggctgcgct gcctggggtg ggggccaggt cgcggggagc tgagctggag ccgggacgga1020cgcgccctgg aggcggcgga atcggaggga gccgagacgc cccggatgcg ctcagagggc1080gaccagctgc tcatcgtgcg ccctgtgcgc agcgaccacg cccggtacac ttgccgcgtc1140cgcagcccct tcggccacag ggaggctgcc gccgacgtca gcgtcttcta cggcccggac1200ccgccgacca tcacggtctc ctcggaccgc gacgccgcgc ctgcccgctt tgtcaccgcg1260ggcagtaacg tgaccttgcg ctgcgccgcc gcctcgcggc cgcccgccga catcacgtgg1320agcctggcgg acccggccga ggccgcggtg cccgcggggt cgcgcctcct gctgcccgcg1380gtcggaccgg gccacgcagg cacctacgcc tgcctggcgg cgaacccgcg taccggccgc1440cgccgccgct cgctgctcaa ccttacagtg gcggacctgc cccccggggc cccacagtgc1500tcagttgaag ggggtcccgg ggaccgcagc ctccgcttcc gctgctcgtg gcccggcggg1560gcccctgctg cctccctgca gttccagggt ctccccgaag gcatccgcgc cgggccagtg1620tcctctgtgc tgctggcggc cgtccccgcc cacccccggc tcagcggcgt ccccatcacc1680tgccttgctc gccacctggt ggccacgcgt acctgcacag tcacgccgga ggccccccga1740gaggtgctgc tgcatccgct ggtggcagag acacggttgg gggaggcaga ggtggcactg1800gaggcctctg gttgtccccc accctcacgg gcatcctggg cccgggaagg gaggcccctg1860gctccaggag gcgggagtcg cctgcggctc agtcaagatg ggcggaaact ccacatcggc1920aacttcagcc tggattggga cctgggaaat tactccgtgc tgtgcagtgg ggcgctgggt1980gctggcggtg accagatcac cctcattgat gggcctgctc tgggcaggac ttccacctac2040agggactggg tctccctgct catcctgggg cctcaggagc ggtcagccgt ggtgcccctt2100ccacctcgga acccagggac ctggaccttt cggatcctgc ccatcctggg gggccagcca2160gggactccat cacaaagccg ggtctaccgg gccggcccca cgttgagcca tggggccatc2220gctggcatcg tcctgggctc cctgctgggc ctggcgctgc tagccgtact tctcctcctt2280tgcatctgct gcctgtgccg ctttcgtgga aagactcctg agaaaaagaa gcatccttct2340accttggtcc ccgtggtcac cccctcagaa aagaagatgc atagtgtgac cccagtggag2400atttcatggc ctctggacct caaagtccct ctggaggacc acagctcaac tagggcctac2460caagccacag accccagttc agttgtctct gtaggcggag gctcaaagac tgttcgcgca2520gccacacagg tgtga 2535
<210>18<211>2349<212>DNA<213>人(Homo sapiens)<400>18atggacaacc cacaggctct gccactcttc ctactcctgg cctccttggt agggatcctc 60accctcagag cctcttctgg acttcagcaa accaacttct cctctgcctt ctcttcagac 120tcaaagagct cttcccaggg gctgggtgtg gaagttccct ccatcaaacc tcccagctgg 180aaagttccag atcagttcct ggattcaaaa gcctctgctg gaatctctga ttccagctgg 240tttcctgagg ccctgagttc caacatgtct gggtccttct ggtcaaatgt ttctgctgag 300ggccaagatt tgagcccggt ttcccccttc tctgaaaccc ctggttctga agtatttcct 360gatatttcgg atcctcaagt tcctgccaaa gaccccaagc cttccttcac tgttaagacc 420ccagcttcaa acatttctac tcaagtctcc cataccaaac tgtctgttga ggccccagat 480tcaaaattct ccccggatga tatggatctt aaactctctg cccagagccc tgaatccaaa 540ttttctgcag agacccactc agctgcaagc tttccccagc aggtgggggg cccactcgct 600gtgctggtgg ggaccaccat ccggctcccc ctagtcccaa tccccaaccc tgggcccccc 660acctctctgg tggtctggcg ccggggctca aaggtgctgg cagctggggg cctggggcca 720ggggcacctc tgatcagcct ggaccctgct caccgagacc acctgcgatt tgaccaggcc 780cggggggttc tggagctcgc ctctgcccag ctggacgatg caggggtcta cacggctgag 840gtcatccggg caggggtctc ccagcagact cacgagttca cggtgggtgt gtatgagccc 900ctaccccagc tgtcggttca gcccaaggct ccagagacag aggagggggc ggccgagctc 960cggctgcgct gcctggggtg ggggccaggt cgcggggagc tgagctggag ccgggacgga1020cgcgccctgg aggcggcgga atcggaggga gccgagacgc cccggatgcg ctcagagggc1080gaccagctgc tcatcgtgcg ccctgtgcgc agcgaccacg cccggtacac ttgccgcgtc1140cgcagcccct tcggccacag ggaggctgcc gccgacgtca gcgtcttcta cggcccggac1200ccgccgacca tcacggtctc ctcggaccgc gacgccgcgc ctgcccgctt tgtcaccgcg1260ggcagtaacg tgaccttgcg ctgcgccgcc gcctcgcggc cgcccgccga catcacgtgg1320agcctggcgg acccggccga ggccgcggtg cccgcggggt cgcgcctcct gctgcccgcg1380gtcggaccgg gccacgcagg cacctacgcc tgcctggcgg cgaacccgcg taccggccgc1440cgccgccgct cgctgctcaa ccttacagtg gcggacctgc cccccggggc cccacagtgc1500tcagttgaag ggggtcccgg ggaccgcagc ctccgcttcc gctgctcgtg gcccggcggg1560gcccctgctg cctccctgca gttccagggt ctccccgaag gcatccgcgc cgggccagtg1620tcctctgtgc tgctggcggc cgtccccgcc cacccccggc tcagcggcgt ccccatcacc1680tgccttgctc gccacctggt ggccacgcgt acctgcacag tcacgccgga ggccccccga1740gaggtgctgc tgcatccgct ggtggcagag acacggttgg gggaggcaga ggtggcactg1800gaggcctctg gttgtccccc accctcacgg gcatcctggg cccgggaagg gaggcccctg1860gctccaggag gcgggagtcg cctgcggctc agtcaagatg ggcggaaact ccacatcggc1920aacttcagcc tggattggga cctgggaaat tactccgtgc tgtgcagtgg ggcgctgggt1980gctggcggtg accagatcac cctcattggc cccacgttga gccatggggc catcgctggc2040atcgtcctgg gctccctgct gggcctggcg ctgctagccg tacttctcct cctttgcatc2100tgctgcctgt gccgctttcg tggaaagact cctgagaaaa agaagcatcc ttctaccttg2160gtccccgtgg tcaccccctc agaaaagaag atgcatagtg tgaccccagt ggagatttca2220tggcctctgg acctcaaagt ccctctggag gaccacagct caactagggc ctaccaagcc2280acagacccca gttcagttgt ctctgtaggc ggaggctcaa agactgttcg cgcagccaca2340caggtgtga2349<210>19<211>789<212>DNA<213>人(Homo sapiens)<400>19atggactctc ttgttacagc aaacaccaaa ttttgctttg atctttttca agagataggc 60aaagatgatc gtcataaaaa catatttttc tctcccctga gcctctcagc tgcccttggt 120atggtacgct tgggtgctag aagtgacagt gcacatcaga ttgatgaggc tgggtcctta 180aacaatgaga gcggactggt cagctgctac tttgggcagc ttctctccaa attagacagg 240atcaagactg attacacact gagtattgcc aacaggcttt atggagagca ggaattccca 300atctgtcagg aatacttaga tggtgtgatt caattttacc acacgacgat tgaaagtgtt 360gatttccaaa aaaaccctga aaaatccaga caagagatta acttctgggt tgaatgtcaa 420tcccaaggta aaatcaagga actcttcagc aaggacgcta ttaatgctga gactgtgctg 480gtactggtga atgctgttta cttcaaggcc aaatgggaaa catactttga ccatgaaaac 540acggtggatg cacctttctg tctaaatgcg aatgaaaaca agagtgtgaa gatgatgacg 600caaaaaggcc tctacagaat tggcttcata gaggaggtga aggcacagat cctggaaatg 660aggtacacca aggggaagct cagcatgttc gtgctgctgc catctcactc taaagataac 720ctgaagggtc tggaagaggt aaatcttcat ttccacatct ctacaaaata tttaatgata 780gatctttag 789<210>20<211>1185<212>DNA<213>人(Homo sapiens)<400>20atggactctc ttgttacagc aaacaccaaa ttttgctttg atctttttca agagataggc 60aaagatgatc gtcataaaaa catatttttc tctcccctga gcctctcagc tgcccttggt 120atggtacgct tgggtgctag aagtgacagt gcacatcaga ttgatgaggt actacacttc 180aacaaaacga cagagcctct ggatcagcag gctgggtcct taaacaatga gagcggactg 240gtcagctgct actttgggca gcttctctcc aaattagaca ggatcaagac tgattacaca 300ctgagtattg ccaacaggct ttatggagag caggaattcc caatctgtca ggaatactta 360gatggtgtga ttcaatttta ccacacgacg attgaaagtg ttgatttcca aaaaaaccct 420gaaaaatcca gacaagagat taacttctgg gttgaatgtc aatcccaagg taaaatcaag 480gaactcttca gcaaggacgc tattaatgct gagactgtgc tggtactggt gaatgctgtt 540tacttcaagg ccaaatggga aacatacttt gaccatgaaa acacggtgga tgcacctttc 600tgtctaaatg cgaatgaaaa caagagtgtg aagatgatga cgcaaaaagg cctctacaga 660attggcttca tagaggaggt gaaggcacag atcctggaaa tgaggtacac caaggggaag 720ctcagcatgt tcgtgctgct gccatctcac tctaaagata acctgaaggg tctggaagag 780cttgaaagga aaatcaccta tgaaaaaatg gtggcctgga gcagctcaga aaacatgtca 840gaagaatcgg tggtcctgtc cttcccccgg ttcaccctgg aagacagcta tgatctcaat 900tccattttac aagacatggg cattacggat atctttgatg aaacgagggc tgatcttact 960ggaatctctc caagtcccaa tttgtacttg tcaaaaatta tccacaaaac ctttgtggag1020gtggatgaaa acggtaccca ggcagctgca gccactgggg ctgttgtctc ggaaaggtca1080ctacgatctt gggtggagtt taatgccaac cacccttttc tctttttcat tagacacaac1140aaaacccaaa ccattctctt ttatggcagg gtctgctctc cttaa1185<210>21<211>1416<212>DNA<213>人(Homo sapiens)<400>21atgtcggtgc cgctgctcaa gatcggggtc gtgctgagca ccatggccat gatcactaac 60tggatgtccc agacgctgcc ctcgctggtg ggcctcaaca ccaccaagct ctcggcggcc 120ggcggcggga cgctggaccg cagcaccggc gtgctgccca ccaaccctga ggagagctgg 180caggtgtaca gctctgccca ggacagcgag ggcaggtgta tctgcacagt ggtcgctcca 240cagcagacca tgtgttcacg ggatgcccgc acaaaacagc tgaggcagct actggagaag 300gtgcagaaca tgtctcaatc catagaggtc ttggacaggc ggacccagag agacttgcag 360tacgtggaga agatggagaa ccaaatgaaa ggactggagt ccaagttcaa acaggcgata 420aaagcgaaaa tggatgaact taggcctttg atacctgtgt tggaagagta caaggccgat 480gccaaattgg tattgcagtt taaagaggag gtccagaatc tgacgtcagt gcttaacgag 540ctgcaagagg aaattggcgc ctatgactac gatgaacttc agagcagagt gtccaatctt 600gaagaaaggc tccgtgcatg catgcaaaaa ctagcttgcg ggaagttgac gggcatcagt 660gaccccgtga ctgtcaagac ctccggctcg aggttcggat cctggatgac agaccctctc 720gcccctgaag gcgataaccg ggtgtggtac atggacggct atcacaacaa ccgcttcgta 780cgtgagtaca agtccatggt tgacttcatg aacacggaca atttcacctc ccaccgtctc 840ccccacccct ggtcgggcac ggggcaggtg gtctacaacg gttctatcta cttcaacaag 900ttccagagcc acatcatcat caggtttgac ctgaagacag agaccatcct caagacccgc 960agcctggact atgccggtta caacaacatg taccactacg cctggggtgg ccactcggac1020atcgacctca tggtggacga gagcgggctg tgggccgtgt acgccaccaa ccagaacgct1080ggcaacatcg tggtcagtag gctggacccc gtgtccctgc agaccctgca gacctggaac1140acgagctacc ccaagcgcag cgccggggag gccttcatca tctgcggcac gctgtacgtc1200accaacggct actcaggggg taccaaggtc cactatgcat accagaccaa tgcctccacc1260tatgaataca tcgacatccc attccagaac aaatactccc acatctccat gctggactac1320aaccccaagg accgggccct gtatgcctgg aacaacggcc accagatcct ctacaacgtg1380accctcttcc acgtcatccg ctccgacgag ttgtag 1416<210>22<211>1458<212>DNA<213>人(Homo sapiens)<400>22atgtcggtgc cgctgctcaa gatcggggtc gtgctgagca ccatggccat gatcactaac 60tggatgtccc agacgctgcc ctcgctggtg ggcctcaaca ccaccaagct ctcggcggcc 120ggcggcggga cgctggaccg cagcaccggc gtgctgccca ccaaccctga ggagagctgg 180caggtgtaca gctctgccca ggacagcgag ggcaggtgta tctgcacagt ggtcgctcca 240cagcagacca tgtgttcacg ggatgcccgc acaaaacagc tgaggcagct actggagaag 300gtgcagaaca tgtctcaatc catagaggtc ttggacaggc ggacccagag agacttgcag 360tacgtggaga agatggagaa ccaaatgaaa ggactggagt ccaagttcaa acaggtggag 420gagattataa gctacacctg gcccaggcag tttaaggcga taaaagcgaa aatggatgaa 480cttaggcctt tgatacctgt gttggaagag tacaaggccg atgccaaatt ggtattgcag 540tttaaagagg aggtccagaa tctgacgtca gtgcttaacg agctgcaaga ggaaattggc 600gcctatgact acgatgaact tcagagcaga gtgtccaatc ttgaagaaag gctccgtgca 660tgcatgcaaa aactagcttg cgggaagttg acgggcatca gtgaccccgt gactgtcaag 720acctccggct cgaggttcgg atcctggatg acagaccctc tcgcccctga aggcgataac 780cgggtgtggt acatggacgg ctatcacaac aaccgcttcg tacgtgagta caagtccatg 840gttgacttca tgaacacgga caatttcacc tcccaccgtc tcccccaccc ctggtcgggc 900acggggcagg tggtctacaa cggttctatc tacttcaaca agttccagag ccacatcatc 960atcaggtttg acctgaagac agagaccatc ctcaagaccc gcagcctgga ctatgccggt1020tacaacaaca tgtaccacta cgcctggggt ggccactcgg acatcgacct catggtggac1080gagagcgggc tgtgggccgt gtacgccacc aaccagaacg ctggcaacat cgtggtcagt1140aggctggacc ccgtgtccct gcagaccctg cagacctgga acacgagcta ccccaagcgc1200agcgccgggg aggccttcat catctgcggc acgctgtacg tcaccaacgg ctactcaggg1260ggtaccaagg tccactatgc ataccagacc aatgcctcca cctatgaata catcgacatc1320ccattccaga acaaatactc ccacatctcc atgctggact acaaccccaa ggaccgggcc1380ctgtatgcct ggaacaacgg ccaccagatc ctctacaacg tgaccctctt ccacgtcatc1440cgctccgacg agttgtag 1458<210>23<211>861<212>DNA<213>人(Homo sapiens)<400>23atgctgcatc tgctggcgct cttcctgcac tgcctccctc tggcctctgg ggactatgac 60atctgcaaat cctgggtgac cacagatgag ggccccacct gggagttcta cgcctgccag 120cccaaggtga tgcgcctgaa ggactacgtc aaggtgaagg tggagccctc aggcatcaca 180tgtggagacc cccctgagag gttctgctcc catgagaatc cctacctatg cagcaacgag 240tgtgacgcct ccaacccgga cctggcccac ccgcccaggc tcatgttcga caaggaggag 300gagggcctgg ccacctactg gcagagcatc acctggagcc gctaccccag cccgctggaa 360gccaacatca ccctttcgtg gaacaagacc gtggagctga ccgacgacgt ggtgatgacc 420ttcgagtacg gccggcccac ggtcatggtc ctggagaagt ccctggacaa cgggcgcacc 480tggcagccct accagttcta cgccgaggac tgcatggagg ccttcggtat gtccgcccgc 540cgggcccgcg acatgtcatc ctccagcgcg caccgcgtgc tctgcaccga ggagtactcg 600cgctgggcag gctccaagaa ggagaagcac gtgcgcttcg aggtgcggga ccgcttcgcc 660atctttgccg gccccgacct gcgcaacatg gacaacctct acacgcggct ggagagcgcc 720aagggcctca aggagttctt caccctcacc gacctgcgca tgcggctgct gcgcccggcg 780ctgggcggca cctatgtgca gcgggagaac ctctacaagt acttctacgc catctccaac 840atcgaggtca tcggcaggta a 861<210>24<211>1602<212>DNA<213>人(Homo sapiens)<400>24atgctgcatc tgctggcgct cttcctgcac tgcctccctc tggcctctgg ggactatgac 60atctgcaaat cctgggtgac cacagatgag ggccccacct gggagttcta cgcctgccag 120cccaaggtga tgcgcctgaa ggactacgtc aaggtgaagg tggagccctc aggcatcaca 180tgtggagacc cccctgagag gttctgctcc catgagaatc cctacctatg cagcaacgag 240tgtgacgcct ccaacccgga cctggcccac ccgcccaggc tcatgttcga caaggaggag 300gagggcctgg ccacctactg gcagagcatc acctggagcc gctaccccag cccgctggaa 360gccaacatca ccctttcgtg gaacaagacc gtggagctga ccgacgacgt ggtgatgacc 420ttcgagtacg gccggcccac ggtcatggtc ctggagaagt ccctggacaa cgggcgcacc 480tggcagccct accagttcta cgccgaggac tgcatggagg ccttcggtat gtccgcccgc 540cgggcccgcg acatgtcatc ctccagcgcg caccgcgtgc tctgcaccga ggagtactcg 600cgctgggcag gctccaagaa ggagaagcac gtgcgcttcg aggtgcggga ccgcttcgcc 660atctttgccg gccccgacct gcgcaacatg gacaacctct acacgcggct ggagagcgcc 720aagggcctca aggagttctt caccctcacc gacctgcgca tgcggctgct gcgcccggcg 780ctgggcggca cctatgtgca gcgggagaac ctctacaagt acttctacgc catctccaac 840atcgaggtca tcggcaggtg caagtgcaac ctgcacgcca acctgtgctc catgcgcgag 900ggcagcctgc agtgcgagtg cgagcacaac accaccggcc ccgactgcgg caagtgcaag 960aagaatttcc gcacccggtc ctggcgggcc ggctcctacc tgccgctgcc ccatggctct1020cccaacgcct gtacgcctcc ctccccaagg gagctgggag cagactgcga atgctacggt1080cactccaacc gctgcagcta cattgacttc ctgaatgtgg tgacctgcgt cagctgcaag1140cacaacacgc gaggtcagca ctgccagcac tgccggctgg gctactaccg caacggctcg1200gcagagctgg atgatgagaa cgtctgcatt gagtgtaact gcaaccagat aggctccgtg1260cacgaccggt gcaacgagac cggcttctgc gagtgccgcg agggcgcggc gggccccaag1320tgcgacgact gcctccccac gcactactgg cgccagggct gctaccccaa cgtgtgcgac1380gacgaccagc tgctgtgcca gaacggaggc acctgcctgc agaaccagcg ctgcgcctgc1440ccgcgcggct acaccggcgt gcgctgcgag cagccccgct gcgaccccgc cgacgatgac1500ggcggtctgg actgcgaccg cgcgcccggg gccgccccgc gccccgccac cctgctcggc1560tgcctgctgc tgctggggct ggccgcccgc ctgggccgct ga 1602<210>25<211>1488<212>DNA<213>人(Homo sapiens)<400>25atgtttgcga acagtccagg gtgctccaac atgcttcatt atgtttactg tgcctgtggc 60catggtttgc agctggtgag aagtgtgtca agctctgtgg atgaaggagg cacatgccat 120tgtatggttc acctacccaa caaccccatc cccctggagc agctggaaca gctacaaagt 180acagctcagg agctcatttg caagtatgag cagaagctgt ctagatgtgc acgcgccatt 240gaagataaag acaatgaggt tctggaaatg agtcacatgc tgaagtcctg gaatcccagt 300gcccttgctt ctccctatga gaacccaggc ttcaacctgc tgtgcctgga gctggaggga 360gcacaggagt tggtgactca acttaaagcc atgggaggtg ttagtgtggc tggggacctc 420ctccaccaac ttcagagcca ggtgactaac gccagtctca cactcaaact tttggctgac 480tctgaccagt gcagctttgg tgctctccag caggaggtgg atgtccttga gagtcaacta 540agtgaatgtg agagagaaaa ggagaaagaa ggcctttgga caccctggac cacccctccc 600cccgcttctt gtgcccatgg aggcctccag gaagttagca aatcccttgt ggtgcagctc 660actcggagag gcttctcata taaggcaggt ccctggggcc gagactcagc acccaatcca 720gcctcttccc tttactgggt tgctcctcta cgtacagatg gcaggtactt tgactactat 780cggctgcccc catcctataa tgacctcgca ctgatgaaaa actatgaaga gaggaagatg 840ggctatggtg atggcagtgg aaacgttgtg tacaagaact ttatgtactt taactactgt 900ggcacaagtg acatggccaa aatggacctt tcctccaaca cactggtgct gtggcgtctg 960ctgcctggtg ccacctataa caaccgcttt tcctgtgctg gtgtgccctg gaaggactta1020gattttgctg gtgatgagaa ggggctgtgg gttctgtatg ccactgagga gagcaagggc1080aacctggttg tgagtcgtct caacgctagc accctagaag tggagaaaac ctggcgtacc1140agccagtaca agccagccct gtcaggggcc ttcatggcct gtggggtgct ctatgcctta1200cactcactga acacccacca agaggagatc ttctatgctt ttgacaccac caccgggcag1260gagcgccgcc tcagcatcct gttggacaag atgctggaaa agctgcaggg catcaactac1320tgcccctcag accacaagcc gtatgtcttc agtgatggtt acctgataaa ttatgacctc1380accttcctga caatgaagac caggctacca agaccaccca ccaggaggcc ctctggggct1440catgctccac caaaacctgt caaacctaac gaggcttcca gaccctga 1488<210>26<211>1053<212>DNA<213>人(Homo sapiens)<400>26atgagaaatc ataagaaggt gactaacgcc agtctcacac tcaaactttt ggctgactct 60gaccagtgca gctttggtgc tctccagcag gaggtggatg tccttgagag tcaactaagt 120gaatcttctt gtgcccatgg aggcctccag gaagttagca aatcccttgt ggtgcagctc 180actcggagag gcttctcata taaggcaggt ccctggggcc gagactcagc acccaatcca 240gcctcttccc tttactgggt tgctcctcta cgtacagatg gcagttatgg ctgtcaccca 300ataattctga atgcagggac ttggcctagg tactttgact actatcggct gtgcaaatcc 360tataatgacc tcgcactgct gaaaaactat gaagagagga agatgggcta tggtgatggc 420agtggaaacg ttgtgtacaa gaactttatg tactttaact actgtggcac aagtgacatg 480gccaaaatgg acctttcctc caacacactg gtgctgtggc gtctgctgcc tggtgccacc 540tataacaacc gcttttcctg tgctggtgtg ccctggaagg acttagattt tgctggtgat 600gagaaggggc tgtgggttct gtatgccact gaggagagca agggcaacct ggttgtgagt 660cgtctcaacg ctagcaccct agaagtggag aaaacctggc gtaccagcca gtacaagcca 720gccctgtcag gggccttcat ggcctgtggg gtgctctatg ccttacactc actgaacacc 780caccaagagg agatcttcta tgcttttgac accaccaccg ggcaggagcg ccgcctcagc 840atcctgttgg acaagatgct ggaaaagctg cagggcatca actactgccc ctcagaccac 900aagccgtatg tcttcagtga tggttacctg ataaattatg acctcacctt cctgacaatg 960aagaccaggc taccaagacc acccaccagg aggccctctg gggctcatgc tccaccaaaa1020cctgtcaaac ctaacgaggc ttccagaccc tga 1053<210>27<211>1860<212>DNA<213>人(Homo sapiens)<400>27atgggccgtg gtcgagccct tcttcccatt gagatgctgc aactgtcctt acgggaagaa 60agtgacacgg caaggatggg ggcccaggag cagattggtc tgcaggatga gatacaagct 120gcaaatgcag gaattagtgg gtccccagga gtggacgggg tagtggacgg tggatcttcc 180aggggtgacc cggccctgac agtgtctgtg tgtgaagttc ctcctgtgag gtcaccgttc 240agaacccacc cccaacttcc tgtgcggctt cctcgaaatc ttgagttctc agttcctgag 300agaagaaccc tgaggaacag acttacctca gcaaccctgg cacctccaac ccgacacatg 360ctactgctgc tgctactgct gccacccctg ctctgtggga gagtgggggc taaggaacag 420aaggattacc tgctgacaat gcagaagtcc gtgacggtgc aggagggcct gtgtgtctct 480gtgctttgct ccttctccta cccccaaaat ggctggactg cctccgatcc agttcatggc 540tactggttcc gggcagggga ccatgtaagc cggaacattc cagtggccac aaacaaccca 600gctcgagcag tgcaggagga gactcgggac cgattccacc tccttgggga cccacagaac 660aaggattgta ccctgagcat cagagacacc agagagagtg atgcagggac atacgtcttt 720tgtgtagaga gaggaaatat gaaatggaat tataaatatg accagctctc tgtgaatgtg 780acagccctga ctcacatgcc caccttctcc atcccgggga ccctggagtc tggccacccc 840aggaacctga cctgctctgt gccctgggcc tgtgaacagg ggacgccccc cacgatcacc 900tggatggggg cctccgtgtc ctccctggac cccactatca ctcgctcctc gatgctcagc 960ctcatcccac agccccagga ccatggcacc agcctcacct gtcaggtgac cttgcctggg1020gccggcgtga ccatgaccag ggctgtccga ctcaacatat cctatcctcc tcagaacttg1080accatgactg tcttccaagg agatggcaca gcatccacaa ccttgaggaa tggctcggcc1140ctttcagtcc tggagggcca gtccctgcac cttgtctgtg ctgtcgacag caatccccct1200gccaggctga gctggacctg ggggagcctg accctgagcc cctcacagtc ctcgaacctt1260ggggtgctgg agctgcctcg agtgcatgtg aaggatgaag gggaattcac ctgccgagct1320cagaaccctc taggctccca gcacatttcc ctgagcctct ccctgcaaaa cgagtacaca1380ggcaaaatga ggcctatatc aggagtgacg ctaggggcat tcgggggagc tggagccaca1440gccctggtct tcctgtactt ctgcatcatc ttcgttgtag tgaggtcctg caggaagaaa1500tcggcaaggc cagcagtggg cgtgggggat acaggcatgg aggacgcaaa cgctgtcagg1560ggctcagcct ctcagatgga ggaaggaact cctgggcctc cttcctggat gctctctggt1620gcatgctggc cccactgctc tgcactgact cccttctctt cctccattca gggacccctg1680attgaatccc cggcagatga cagcccccca caccatgctc cgccagccct ggccaccccc1740tccccagagg aaggagagat ccagtatgca tccctcagct tccacaaagc gaggcctcag1800tacccacagg aacaggaggc catcggctat gagtactccg agatcaacat ccccaagtga1860<210>28<211>1473<212>DNA<213>人(Homo sapiens)<400>28atgctactgc tgctgctact gctgccaccc ctgctctgtg ggagagtggg ggctaaggaa 60cagaaggatt acctgctgac aatgcagaag tccgtgacgg tgcaggaggg cctgtgtgtc 120tctgtgcttt gctccttctc ctacccccaa aatggctgga ctgcctccga tccagttcat 180ggctactggt tccgggcagg ggaccatgta agccggaaca ttccagtggc cacaaacaac 240ccagctcgag cagtgcagga ggagactcgg gaccgattcc acctccttgg ggacccacag 300aacaaggatt gtaccctgag catcagagac accagagaga gtgatgcagg gacatacgtc 360ttttgtgtag agagaggaaa tatgaaatgg aattataaat atgaccagct ctctgtgaat 420gtgacagccc tgactcacat gcccaccttc tccatcccgg ggaccctgga gtctggccac 480cccaggaacc tgacctgctc tgtgccctgg gcctgtgaac aggggacgcc ccccacgatc 540acctggatgg gggcctccgt gtcctccctg gaccccacta tcactcgctc ctcgatgctc 600agcctcatcc cacagcccca ggaccatggc accagcctca cctgtcaggt gaccttgcct 660ggggccggcg tgaccatgac cagggctgtc cgactcaaca tatcctatcc tcctcagaac 720ttgaccatga ctgtcttcca aggagatggc acagcatcca caaccttgag gaatggctcg 780gccctttcag tcctggaggg ccagtccctg caccttgtct gtgctgtcga cagcaatccc 840cctgccaggc tgagctggac ctgggggagc ctgaccctga gcccctcaca gtcctcgaac 900cttggggtgc tggagctgcc tcgagtgcat gtgaaggatg aaggggaatt cacctgccga 960gctcagaacc ctctaggctc ccagcacatt tccctgagcc tctccctgca aaacgagtac1020acaggcaaaa tgaggcctat atcaggagtg acgctagggg cattcggggg agctggagcc1080acagccctgg tcttcctgta cttctgcatc atcttcgttg tagtgaggtc ctgcaggaag1140aaatcggcaa ggccagcagt gggcgtgggg gatacaggca tggaggacgc aaacgctgtc1200aggggctcag cctctcaggg acccctgact gaatcctgga aagatggcaa ccccctgaag1260aagcctcccc cagctgttgc cccctcgtca ggggaggaag gagagctcca ttatgcaacc1320ctcagcttcc ataaagtgaa gcctcaggac ccgcagggac aggaggccac tgacagtgaa1380tactcggaga tcaagatcca caagcgagaa actgcagaga ctcaggcctg tttgaggaat1440cacaacccct ccagcaaaga agtcagaggc tga 1473<210>29<211>1389<212>DNA<213>人(Homo sapiens)<400>29atgctgccac tttggactct ttcactgctg ctgggagcag tagcaggaaa agaagtttgc 60tacgaaagac tcggctgctt cagtgatgac tccccatggt caggaattac ggaaagaccc 120ctccatatat tgccttggtc tccaaaagat gtcaacaccc gcttcctcct atatactaat 180gagaacccaa acaactttca agagatcagt gcggttaatt cttcaactat ccaagcctca 240tattttggaa cagacaagat cacccgtatc aacatagctg gatggaaaac agatggcaaa 300tggcagagag acatgtgcaa tgtgttgcta cagctggaag atataaattg cattaattta 360gattggatca acggttcacg ggaatacatc catgctgtaa acaatctccg tgttgttggt 420gctgaggtgg cttattttat tgatgttctc atgaaaaaat ttgaatattc cccttctaaa 480gtgcacttga ttggccacag cttgggagca cacctggctg gggaagctgg gtcaaggata 540ccaggccttg gaagaataac tggtaagcat gccctgcagt tgggccttga gtgtgcaacc 600gagggctacc tgttatctgc tactctggct aacaatgtca acttcgtaga tacaaatcac 660atggatgcaa ctcccataat cccccagtgg atgaggggca cttcgggaac cagtaaccct 720cttcctgtta cttcctctct gtgcttatgg ttggctgatc ttggctcggt ctcactcgta 780tgtttgtggc ctgaaatggc ttccttcttt gactgtaacc atgcccgaag ttatcaattt 840tatgctgaaa gcattcttaa tcctgatgca tttattgctt atccttgtag atcctacaca 900tcttttaaag caggaaattg cttcttttgt tccaaagaag gttgcccaac aatgggtcat 960tttgctgata gatttcactt caaaaatatg aagactaatg gatcacatta ttttttaaac1020acagggtccc tttccccatt tgcccgttgg aggcacaaat tgtctgttaa actcagtgga1080agcgaagtca ctcaaggaac tgtctttctt cgtgtaggcg gggcagttag gaaaactggg1140gagtttgcca ttgtcagtgg aaaacttgag ccaggcatga cttacacaaa attaatcgat1200gcagatgtta acgttggaaa cattacaagt gttcagttca tctggaaaaa acatttgttt1260gaagattctc agaataagtt gggagcagaa atggtgataa atacatctgg gaaatatgga1320tataaatcta ccttctgtag ccaagacatt atgggaccta atattctcca gaacctgaaa1380ccatgctaa1389<210>30<211>768<212>DNA<213>人(Homo sapiens)<400>30atggtgctgc tgctggtgat cctcatcccg gtgctggtga gctcggccgg cacgtcggcg 60cactacgaga tgctgggcac ctgccgcatg gtctgcgacc cctacggggg caccaaggcg 120cccagcaccg ctgccacgcc cgaccgcggc ctcatgcagt ccctgcccac cttcatccag 180ggccccaaag gcgaggccgg caggcccggg aaggcgggtc cgcgcgggcc ccccggagag 240cccgggccac ccggccccat ggggcccccg ggcgagaagg gcgagccggg ccgccaaggc 300ctgccgggcc cgcccggggc gcccggcctg aacgcggccg gggccatcag cgccgccacc 360tacagcacgg ggcccaagat cgccttctac gccggcctca agcggcagca tgaaggctac 420gaggtgctca agttcgacga cgtggtcacc aacctcggaa accactacga ccccaccacc 480ggcaagttca cctgctccat cccgggcatc tacttcttca cctaccacgt cctgatgcgc 540ggaggggacg gcaccagcat gtgggctgat ctctgcaaaa acaaccaggt gcgtgctagt 600gcaattgccc aagatgctga tcagaattac gactatgcca gtaacagtgt ggttcttcat 660ttggagccgg gagatgaagt ctatatcaaa ttagatggcg ggaaagccca tggaggaaac 720aacaacaaat acagcacgtt ttctggattt attatttatg ctgactga 768<210>31<211>2355<212>DNA<213>人(Homo sapiens)<400>31atggagggcg acggcgggac cccatgggcc ctggcgctgc tgcgcacctt cgacgcgggc 60gagttcacgg gctgggagaa ggtgggctcg ggcggcttcg ggcaggtgta caaggtgcgc 120catgtccact ggaagacctg gctggccatc aagtgctcgc ccagcctgca cgtcgacgac 180agggagcgca tggagctttt ggaagaagcc aagaagatgg agatggccaa gtttcgctac 240atcctgcctg tgtatggcat ctgccgcgaa cctgtcggcc tggtcatgga gtacatggag 300acgggctccc tggaaaagct gctggcttcg gagccattgc catgggatct ccggttccga 360atcatccacg agacggcggt gggcatgaac ttcctgcact gcatggcccc gccactcctg 420cacctggacc tcaagcccgc gaacatcctg ctggatgccc actaccacgt caagatttct 480gattttggtc tggccaagtg caacgggctg tcccactcgc atgacctcag catggatggc 540ctgtttggca caatcgccta cctccctcca gagcgcatca gggagaagag ccggctcttc 600gacaccaagc acgatgtata cagctttgcg atcgtcatct ggggcgtgct cacacagaag 660aagccgtttg cagatgagaa gaacatcctg cacatcatgg tgaaggtggt gaagggccac 720cgccccgagc tgccgcccgt gtgcagagcc cggccgcgcg cctgcagcca cctgatacgc 780ctcatgcagc ggtgctggca gggggatccg cgagttaggc ccaccttcca agaaattact 840tctgaaaccg aggacctgtg tgaaaagcct gatgacgaag tgaaagaaac tgctcatgat 900ctggacgtga aaagcccccc ggagcccagg agcgaggtgg tgcctgcgag gctcaagcgg 960gcctctgccc ccaccttcga taacgactac agcctctccg agctgctctc acagctggac1020tctggagttt cccaggctgt cgagggcccc gaggagctca gccgcagctc ctctgagtcc1080aagctgccat cgtccggcag tgggaagagg ctctcggggg tgtcctcggt ggactccgcc1140ttctcttcca gaggatcact gtcgctgtcc tttgagcggg aaccttcaac cagcgatctg1200ggcaccacag acgtccagaa gaagaagctt gtggatgcca tcgtgtccgg ggacaccagc1260aaactgatga agatcctgca gccgcaggac gtggacctgg cactggacag cggtgccagc1320ctgctgcacc tggcggtgga ggccgggcaa gaggagtgcg ccaagtggct gctgctcaac1380aatgccaacc ccaacctgag caaccgtagg ggctccaccc cgttgcacat ggccgtggag1440aggagggtgc ggggtgtcgt ggagctcctg ctggcgcgga agatcagtgt caacgccaag1500gatgaggacc agtggacagc cctccacttt gcagcccaga acggggacga gtctagcaca1560cggctgctgt tggagaagaa cgcctcggtc aacgaggtgg actttgaggg ccggacgccc1620atgcacgtgg cctgccagca cgggcaggag aatatcgtgc gcatcctgct gcgccgaggc1680gtggacgtga gcctgcaggg caaggatgcc tggctgccac tgcactacgc tgcctggcag1740ggccacctgc ccatcgtcaa gctgctggcc aagcagccgg gggtgagtgt gaacgcccag1800acgctggatg ggaggacgcc attgcacctg gccgcacagc gcgggcacta ccgcgtggcc1860cgcatcctca tcgacctgtg ctccgacgtc aacgtctgca gcctgctggc acagacaccc1920ctgcacgtgg ccgcggagac ggggcacacg agcactgcca ggctgctcct gcatcggggc1980gctggcaagg aggccatgac ctcagacggc tacaccgctc tgcacctggc tgcccgcaac2040ggacacctgg ccactgtcaa gctgcttgtc gaggagaagg ccgatgtgct ggcccgggga2100cccctgaacc agacggcgct gcacctggct gccgcccacg ggcactcgga ggtggtggag2160gagttggtca gcgccgatgt cattgacctg ttcgacgagc aggggctcag cgcgctgcac2220ctggccgccc agggccggca cgcacagacg gtggagactc tgctcaggca tggggcccac2280atcaacctgc agagcctcaa gttccagggc ggccatggcc ccgccgccac gctcctgcgg2340cgaagcaaga cctag 2355<210>32<211>759<212>DNA<213>人(Homo sapiens)<400>32atggcagccc ccgccctgct gctcctagca ctgctgctgc ccgtgggggc ctggcccggg 60ctgcccagga ggccctgtgt gcactgctgc cgcccggcct ggccccctgg accctatgcc 120cgggtgagtg acagggacct gtggaggggg gacctgtgga gggggctgcc tcgagtacgg 180cccactatag acatcgaaat cctcaaaggt gagaagggtg aggccggcgt ccgaggtcgg 240gccggcagga gcgggaaaga ggggccgcca ggcgcccggg gcctgcaggg ccgcagaggc 300cagaaggggc aggtggggcc gccgggcgcc gcgtgccgac gtgcctacgc cgccttctcc 360gtgggccggc gcgagggcct gcacagctcc gaccacttcc aggcggtgcc cttcgacacg 420gagctggtga acctggacgg cgccttcgac ctggccgcgg gccgcttcct ctgcacggtg 480cccggcgtct acttcctcag cctcaacgtg cacacctgga actacaagga gacctacctg 540cacatcatgc tgaaccggcg gcccgcggcc gtgctctacg cgcagcccag cgagcgcagc 600gtcatgcagg cccagagcct gatgctgctg ctggcggcgg gcgacgccgt ctgggtgcgc 660atgttccagc gcgaccggga caacgccatc tacggcgagc acggagacct ctacatcacc 720ttcagcggcc acctggtcaa gccggccgcc gagctgtag759<210>33<211>1782<212>DNA<213>人(Homo sapiens)<400>33atgcccagct cgctgttcgc agacctggag cgcaacggca gcggcggcgg cggcggcggc 60agcagcggag ggggagagac cctggatgac caaagagccc tgcagctcgc gctcgaccag 120ctctccctgc tggggctgga cagtgacgag ggcgcctctc tgtacgacag cgagccgcgc 180aagaagagcg tgaacatgac cgagtgcgtg ccagtaccca gttctgagca tgtcgccgag 240atcgtggggc ggcaaggtag gtcgaggagg gatggggagc tggatcccag cggcatctcc 300ccagatgact tttctgggat tctcgggttt ggttcgggac gactgcagtc actgggggag 360ggccaggcag ccaatgggct gttcctcgag cgcctcgcgg gtgggatccg ctgcccagcc 420cgtggcgcgg cccgaggttg taaaatcaaa gcgctgcggg cgaagaccaa tacttacatc 480aagaccccag ttcgcgggga ggagcctgtc tttgttgtga cgggcaggaa ggaggatgtg 540gccatggctc ggagggagat catctctgct gccgagcact tctccatgat ccgcgcctcc 600cggaataaga acacggcact caacggcgcg gtgcctgggc cgcccaacct gcccgggcag 660accaccatcc aagtgcgggt accctaccgc gtggtggggc tcgtggtggg gcccaaaggc 720gccacaatca agcgcatcca gcagcagacg cacacgtaca tcgtgacgcc cagccgggat 780aaggagccgg tgttcgaggt gaccggcatg ccagagaacg tggatcgcgc tcgagaggag 840attgaggcgc acattgctct gcgtaccggc ggcatcattg agctcacaga cgagaacgac 900ttccacgcca acggcaccga tgtgggcttc gatctgcatc atgggtccgg cggtgcttcc 960acagactctt atttcggcgg cgggaccagc agcagcgcag cggctaccca gcgcctggcg1020gactacagcc cccctagccc cgccctgagc tttgcgcaca acggaaacaa taacaataac1080ggcaatgggt acacctacac agcgggggga gaagcctcag tgccatcccc cgacggctgc1140cccgagctgc agcccacttt tgacccggct cccgctcccc cacctggggc accacttatc1200tgggcccagt tcgagcggtc cccgggaggc ggacctgcag ctccggtatc ttcttcctgc1260tcttcttctg catcttcgtc tgcttcttcc tcctccgtgg tcttccccgg gggtggcgcc1320agtgcgccct ccaacgccaa cctggggcta ttggtgcacc gccggctgca ccctggcacc1380agctgcccgc gcctgtctcc acccttgcac atggccccgg gggcgggaga gcaccacctg1440gctcgccggg tgcgcagcga cccgggtgga ggaggcctgg cctacgccgc ttatgccaac1500gggctggggg cacagctgcc tggcttgcag ccgtcggaca cgtcgggctc ctcctcttcg1560tccagctcct cctccagctc ttcatcctct tcctccgggc ttcggcgtaa aggcagccgc1620gactgctccg tgtgcttcga gagcgaagtg attgccgcgc tggtgccctg tggccacaac1680ctcttctgca tggagtgcgc caatcgcatc tgtgagaaga gcgagcccga gtgcccggtc1740tgccacaccg cggtcactca ggccatccgc atcttttctt aa 1782<210>34<211>1419<212>DNA<213>人(Homo sapiens)<400>34atgcccagct cgctgttcgc agacctggag cgcaacggca gcggcggcgg cggcggcggc 60agcagcggag ggggagagac cctggatgac caaagagccc tgcagctcgc gctcgaccag 120ctctccctgc tggggctgga cagtgacgag ggcgcctctc tgtacgacag cgagccgcgc 180aagaagagcg tgaacatgac cgagtgcgtg ccagtaccca gttctgagca tgtcgccgag 240atcgtggggc ggcaaggttg taaaatcaaa gcgctgcggg cgaagaccaa tacttacatc 300aagaccccag ttcgcgggga ggagcctgtc tttgttgtga cgggcaggaa ggaggatgtg 360gccatggctc ggagggagat catctctgct gccgagcact tctccatgat ccgcgcctcc 420cggaataaga acacggcact caacggcgcg gtgcctgggc cgcccaacct gcccgggcag 480accaccatcc aagtgcgggt accctaccgc gtggtggggc tcgtggtggg gcccaaaggc 540gccacaatca agcgcatcca gcagcagacg cacacgtaca tcgtgacgcc cagccgggat 600aaggagccgg tgttcgaggt gaccggcatg ccagagaacg tggatcgcgc tcgagaggag 660attgaggcgc acattgctct gcgtaccggc ggcatcattg agctcacaga cgagaacgac 720ttccacgcca acggcaccga tgtgggcttc gatctgcatc atgggtccgg cgggtccggc 780ccaggcagcc tctggagcaa gcccaccccc agcatcacgc ccacccccgg ccgcaagcct 840ttctctagct accgcaacga cagctccagc tcgcttggca gtgcttccac agactcttat 900ttcggcggcg ggaccagcag cagcgcagcg gctacccagc gcctggcgga ctacagccct 960gcgccctcca acgccaacct ggggctattg gtgcaccgcc ggctgcaccc tggcaccagc1020tgcccgcgcc tgtctccacc cttgcacatg gccccggggg cgggagagca ccacctggct1080cgccgggtgc gcagcgaccc gggtggagga ggcctggcct acgccgctta tgccaacggg1140ctgggggcac agctgcctgg cttgcagccg tcggacacgt cgggctcctc ctcttcgtcc1200agctcctcct ccagctcttc atcctcttcc tccgggcttc ggcgtaaagg cagccgcgac1260tgctccgtgt gcttcgagag cgaagtgatt gccgcgctgg tgccctgtgg ccacaacctc1320ttctgcatgg agtgcgccaa tcgcatctgt gagaagagcg agcccgagtg cccggtctgc1380cacaccgcgg tcactcaggc catccgcatc ttttcttaa 1419<210>35<211>1824<212>DNA<213>人(Homo sapiens)
<400>35atgtggggcc tggtgaggct cctgctggcc tggctgggtg gctggggctg catggggcgt 60ctggcagccc cagcccgggc ctgggcaggg tcccgggaac acccagggcc tgctctgctg 120cggactcgaa ggagctgggt ctggaaccag ttctttgtca ttgaggaata tgctggtcca 180gagcctgttc tcattggcaa gctgcactcg gatgttgacc ggggagaggg ccgcaccaag 240tacctgttga ccggggaggg ggcaggcacc gtatttgtga ttgatgaggc cacaggcaat 300attcatgtta ccaagagcct tgaccgggag gaaaaggcgc aatatgtgct actggcccaa 360gccgtggacc gagcctccaa ccggcccctg gagcccccat cagagttcat catcaaagtg 420caagacatca acgacaatcc acccattttt ccccttgggc cctaccatgc caccgtgccc 480gagatgtcca atgtcgggac atcagtgatc caggtgactg ctcacgatgc tgatgacccc 540agctatggga acagtgccaa gctggtgtac actgttctgg atggactgcc tttcttctct 600gtggaccccc agactggagt ggtgcgtaca gccatcccca acatggaccg ggagacacag 660gaggagttct tggtggtgat ccaggccaag gacatgggcg gccacatggg ggggctgtca 720ggcagcacta cggtgactgt cacgctcagc gatgtcaacg acaacccccc caagttccca 780cagagcctat accagttctc cgtggtggag acagctggac ctggcacact ggtgggccgg 840ctccgggccc aggacccaga cctgggggac aacgccctga tggcatacag catcctggat 900ggggaggggt ctgaggcctt cagcatcagc acagacttgc agggtcgaga cgggctcctc 960actgtccgca agcccctaga ctttgagagc cagcgctcct actccttccg tgtcgaggcc1020accaacacgc tcattgaccc agcctatctg cggcgagggc ccttcaagga tgtggcctct1080gtgcgtgtgg cagtgcaaga tgccccagag ccacctgcct tcacccaggc tgcctaccac1140ctgacagtgc ctgagaacaa ggccccgggg accctggtag gccagatctc cgcggctgac1200ctggactccc ctgccagccc aatcagatac tccatcctcc cccactcaga tccggagcgt1260tgcttctcta tccagcccga ggaaggcacc atccatacag cagcacccct ggatcgcgag1320gctcgcgcct ggcacaacct cactgtgctg gctacagagc tcgtccctta tacccctgct1380tatgcctcag gggctcctcc acccttttgt cttcatactg catatgaaaa ctgcccttgt1440atatgtggat atctgaatgt gtcagtgaag gcctatatga atgtgcacat gtgggccatg1500gtcttagtct ttgcagaaca caaaggagga gggagaggac cagggaggca ggctgttgac1560ggacagaagc agtcaactag gtgggagctg agccagaact gcaattatct cccaaagtcc1620agagaagggg tccacccagg aaccagcatg agagctcagg cctctcaact ccagggctcc1680agaggcacac acaggaactg cacacgcatc gcctgccaca ctcgtgtgaa tcccatcctg1740tatcactcac ctacacctgg gcacagaact acatacacct gtggacatga atatgcaccc1800tcttatgccg agtcaaacac ctga 1824<210>36<211>2346<212>DNA<213>人(Homo sapiens)<400>36atgtggggcc tggtgaggct cctgctggcc tggctgggtg gctggggctg catggggcgt 60ctggcagccc cagcccgggc ctgggcaggg tcccgggaac acccagggcc tgctctgctg 120cggactcgaa ggagctgggt ctggaaccag ttctttgtca ttgaggaata tgctggtcca 180gagcctgttc tcattggcaa gctgcactcg gatgttgacc ggggagaggg ccgcaccaag 240tacctgttga ccggggaggg ggcaggcacc gtatttgtga ttgatgaggc cacaggcaat 300attcatgtta ccaagagcct tgaccgggag gaaaaggcgc aatatgtgct actggcccaa 360gccgtggacc gagcctccaa ccggcccctg gagcccccat cagagttcat catcaaagtg 420caagacatca acgacaatcc acccattttt ccccttgggc cctaccatgc caccgtgccc 480gagatgtcca atgtcgggac atcagtgatc caggtgactg ctcacgatgc tgatgacccc 540agctatggga acagtgccaa gctggtgtac actgttctgg atggactgcc tttcttctct 600gtggaccccc agactggagt ggtgcgtaca gccatcccca acatggaccg ggagacacag 660gaggagttct tggtggtgat ccaggccaag gacatgggcg gccacatggg ggggctgtca 720ggcagcacta cggtgactgt cacgctcagc gatgtcaacg acaacccccc caagttccca 780cagagcctat accagttctc cgtggtggag acagctggac ctggcacact ggtgggccgg 840ctccgggccc aggacccaga cctgggggac aacgccctga tggcatacag catcctggat 900ggggaggggt ctgaggcctt cagcatcagc acagacttgc agggtcgaga cgggctcctc 960actgtccgca agcccctaga ctttgagagc cagcgctcct actccttccg tgtcgaggcc1020accaacacgc tcattgaccc agcctatctg cggcgagggc ccttcaagga tgtggcctct1080gtgcgtgtgg cagtgcaaga tgccccagag ccacctgcct tcacccaggc tgcctaccac1140ctgacagtgc ctgagaacaa ggccccgggg accctggtag gccagatctc cgcggctgac1200ctggactccc ctgccagccc aatcagatac tccatcctcc cccactcaga tccggagcgt1260tgcttctcta tccagcccga ggaaggcacc atccatacag cagcacccct ggatcgcgag1320gctcgcgcct ggcacaacct cactgtgctg gctacagagc tcgacagttc tgcacaggcc1380tcgcgcgtgc aagtggccat ccagaccctg gatgagaatg acaatgctcc ccagctggct1440gagccctacg atacttttgt gtgtgactct gcagctcctg gccagctgat tcaggtcatc1500cgggccctgg acagagatga agttggcaac agtagccatg tctcctttca aggtcctctg1560ggccctgatg ccaactttac tgtccaggac aaccgagatg gctccgccag cctgctgctg1620ccctcccgcc ctgctccacc ccgccatgcc ccctacttgg ttcccataga actgtgggac1680tgggggcagc cggcgctgag cagcactgcc acagtgactg ttagtgtgtg ccgctgccag1740cctgacggct ctgtggcatc ctgctggcct gaggctcacc tctcagctgc tgggctcagc1800accggcgccc tgcttgccat catcacctgt gtgggtgccc tgcttgccct ggtggtgctc1860ttcgtggccc tgcggcggca gaagcaagaa gcactgatgg tactggagga ggaggacgtc1920cgagagaaca tcatcaccta cgacgacgag ggcggcggcg aggaggacac cgaggccttc1980gacatcacgg ccttgcagaa cccggacggg gcggcccccc cggcgcccgg ccctcccgcg2040cgccgagacg tgttgccccg ggcccgggtg tcgcgccagc ccagaccccc cggccccgcc2100gacgtggcgc agctcctggc gctgcggctc cgcgaggcgg acgaggaccc cggcgtaccc2160ccgtacgact cggtgcaggt gtacggctac gagggccgcg gctcctcttg cggctccctc2220agctccctgg gctccggcag cgaagccggc ggcgcccccg gccccgcgga gccgctggac2280gactggggtc cgctcttccg caccctggcc gagctgtatg gggccaagga gcccccggcc2340ccctga 2346<210>37<211>1923<212>DNA<213>人(Homo sapiens)<400>37atggccagag gccattacat ttatgtggat acctcctttg gcaagcaggg ggagaaagct 60gtgctgctaa gtcctgactt acaggctgag gaatggagct gcctccgttt ggtctaccag 120ataaccacat cttcggagtc tctgtcagat cccagccagc tgaacctcta catgagattt 180gaagatgaaa gctttgatcg cttgctttgg tcagctaagg aaccttcaga cagctggctc 240atagccagct tggatttgca aaacagttcc aagaaattca agattttaat agaaggtgta 300ctaggacagg gaaacacagc cagcatcgca ctatttgaaa tcaagatgac aaccggctac 360tgtattgaat gtgactttga agaaaatcat ctctgtggct ttgtgaaccg ctggaatccc 420aatgtgaact ggtttgttgg aggaggaagt attcggaatg tccactccat tctcccacag 480gatcacacct tcaagagtga actgggccac tacatgtacg tggactcagt ttatgtgaag 540cacttccagg aggtggcaca gctcatctcc ccgttgacca cggcccccat ggctggctgc 600ctgtcatttt attaccagat ccagcagggg aatgacaatg tcttttccct ttacactcgg 660gatgtggctg gcctttacga ggaaatctgg aaagcagaca ggccagggaa tgctgcctgg 720aaccttgcgg aggtcgagtt cacatgccat tttcctctgc aggttatttt tgaagttgct 780ttcaatggtc ccaagggagg ttatgttgcc ctggatgata tttcattctc tcctgttcac 840tgccagaatc agacagaact tctgttcagt gccgtggaag ccagctgcaa ttttgagcaa 900gatctctgca acttttacca agataaagaa ggtccaggtt ggacccgagt gaaagtaaaa 960ccaaacatgt atcgggctgg agaccacact acaggcttag ggtattacct gctagccaac1020acaaagttca catctcagcc tggctacatt ggaaggctct atgggccctc cctaccagga1080aacttgcagt attgtctgcg ttttcattat gccatctatg gatttttaaa aatgagtgac1140accctagcag tttacatctt tgaagagaac catgtggttc aagagaagat ctggtctgtg1200ttggagtccc caaggggtgt ttggatgcaa gctgaaatca cctttaagaa gcccatgcct1260accaaggtgg ttttcatgag cctatgcaaa agtttctggg actgtgggct tgtagccctg1320gatgacatta caatacaatt gggaagctgc tcatcttcag agaaacttcc acctccacct1380ggagagtgta ctttcgagca agatgaatgt acatttactc aggagaaaag aaaccggagc1440agctggcaca ggaggagggg agaaactccc acttcctaca caggaccaaa gggagatcac1500actactgggg taggctacta catgtacatt gaggcctccc atatggtgta tggacaaaaa1560gcacgcctct tgtccaggcc tctgcgagga gtctctggaa aacactgctt gacctttttc1620taccacatgt atggaggggg cactggcctg ctgagtgttt atctgaaaaa ggaagaagac1680agtgaagagt ccctcttatg gaggagaaga ggtgaacaga gcatttcctg gctacgagca1740ctgattgaat acagctgtga gaggcaacac cagataattt ttgaagccat tcgaggagta1800tcaataagaa gtgatattgc cattgatgat gttaaatttc aggcaggacc ctgtggagaa1860atggaagata caactcaaca atcatcagga tattctgagg acttaaatga aattgagtat1920taa 1923<210>38<211>2061<212>DNA<213>人(Homo sapiens)<400>38atgctgttaa ggggcgtcct cctggcgttg caagccctgc agctcgccgg tgccctcgac 60ctgcccgctg ggtcctgtgc ctttgaagag agcacttgcg gctttgactc cgtgttggcc 120tctctgccgt ggattttaaa tgaggaaggc cattacattt atgtggatac ctcctttggc 180aagcaggggg agaaagctgt gctgctaagt cctgacttac aggctgagga atggagctgc 240ctccgtttgg tctaccagat aaccacatct tcggagtctc tgtcagatcc cagccagctg 300aacctctaca tgagatttga agatgaaagc tttgatcgct tgctttggtc agctaaggaa 360ccttcagaca gctggctcat agccagcttg gatttgcaaa acagttccaa gaaattcaag 420attttaatag aaggtgtact aggacaggga aacacagcca gcatcgcact atttgaaatc 480aagatgacaa ccggctactg tattgaatgt gactttgaag aaaatcatct ctgtggcttt 540gtgaaccgct ggaatcccaa tgtgaactgg tttgttggag gaggaagtat tcggaatgtc 600cactccattc tcccacagga tcacaccttc aagagtgaac tgggccacta catgtacgtg 660gactcagttt atgtgaagca cttccaggag gtggcacagc tcatctcccc gttgaccacg 720gcccccatgg ctggctgcct gtcattttat taccagatcc agcaggggaa tgacaatgtc 780ttttcccttt acactcggga tgtggctggc ctttacgagg aaatctggaa agcagacagg 840ccagggaatg ctgcctggaa ccttgcggag gtcgagttca catgccattt tcctctgcag 900gttatttttg aagttgcttt caatggtccc aagggaggtt atgttgccct ggatgatatt 960tcattctctc ctgttcactg ccagaatcag acagaacttc tgttcagtgc cgtggaagcc1020agctgcaatt ttgagcaaga tctctgcaac ttttaccaag ataaagaagg tccaggttgg1080acccgagtga aagtaaaacc aaacatgtat cgggctggag accacactac aggcttaggg1140tattacctgc tagccaacac aaagttcaca tctcagcctg gctacattgg aaggctctat1200gggccctccc taccaggaaa cttgcagtat tgtctgcgtt ttcattatgc catctatgga1260tttttaaaaa tgagtgacac cctagcagtt tacatctttg aagagaacca tgtggttcaa1320gagaagatct ggtctgtgtt ggagtcccca aggggtgttt ggatgcaagc tgaaatcacc1380tttaagaagc ccatgcctac caaggtggtt ttcatgagcc tatgcaaaag tttctgggac1440tgtgggcttg tagccctgga tgacattaca atacaattgg gaagctgctc atcttcagag1500aaacttccac ctccacctgg agagtgtact ttcgagcaag atgaatgtac atttactcag1560gagaaaagaa accggagcag ctggcacagg aggaggggag aaactcccac ttcctacaca1620ggaccaaagg gagatcacac tactggggta ggctactaca tgtacattga ggcctcccat1680atggtgtatg gacaaaaagc acgcctcttg tccaggcctc tgcgaggagt ctctggaaaa1740cactgcttga cctttttcta ccacatgtat ggagggggca ctggcctgct gagtgtttat1800ctgaaaaagg aagaagacag tgaagagtcc ctcttatgga ggagaagagg tgaacagagc1860atttcctggc tacgagcact gattgaatac agctgtgaga ggcaacacca gataattttt1920gaagccattc gaggagtatc aataagaagt gatattgcca ttgatgatgt taaatttcag1980gcaggaccct gtggagaaat ggaagataca actcaacaat catcaggata ttctgaggac2040ttaaatgaaa ttgagtatta a 2061<210>39<211>465<212>DNA<213>人(Homo sapiens)<400>39atgaccttgt ccccaacaca gccacctctg tttcacctgc cttacgtcca gaaatgcttt 60atccctactg tggagcagct gactctgggg atcccatgcc agaatcatgg ggagatagac 120catggccagg atatatttcc agcagagaag ctctgtcatc tgcaggattg caaggtgaac 180cttcacagag ctgcctgcgg tgagtgtatt gttgcaccca agacttccag cttcccttac 240tgtcagggga cctgcctgac cctcaacagt gagcttcatc aatccaactt tgcactcaaa 300gtttgcacta taagagggga gtgcctattg atctgttcct ggctctttca gacctgtagt 360cccaccaagg tcattctctt ctccctaacg gtccaggatg acgaacgtaa gatgagcgtt 420cactgtgtga acgcatcctt gatagagaag tgtggctgct cttga 465
<210>40<211>277<212>PRT<213>人(Homo sapiens)<400>40Met Arg Gly Leu Val Met Ala Pro Leu Leu Ile Leu Leu Val Gly Gly1 5 10 15Thr Glu Ala Phe Arg Ile Cys Ala Phe Asn Ala His Arg Leu Thr Leu20 25 30Ala Lys Leu Thr Lys Glu Ser Val Met Asp Thr Leu Val Gln Ile Leu35 40 45Ala Arg Cys Asp Ile Met Val Leu Gln Glu Val Val Asp Ser Ser Gln50 55 60Asn Thr Val Pro Phe Leu Leu Gln Lys Leu Lys Ser Ser Arg Ser Tyr65 70 75 80Ser Phe Leu Asn Ser Ser Leu Leu Gly Arg Ser Thr Tyr Lys Glu Lys85 90 95Tyr Val Tyr Ile Tyr Arg Ser Asp Lys Thr Gln Val Leu Asn Phe Tyr100 105 110Gln Tyr Asn Asp Thr Asp Asp Ile Phe Ala Arg Glu Pro Phe Val Ala115 120 125His Phe Thr Leu Pro Ser Lys Thr Leu Pro Ser Val Val Leu Val Pro130 135 140Leu His Thr Thr Pro Lys Asp Val Glu Lys Glu Leu Asn Ala Leu Tyr145 150 155 160Asp Val Phe Leu Asp Val Tyr Gln Arg Trp Gln Asn Glu Asn Val Ile165 170 175Leu Leu Gly Asp Phe Asn Ala Asp Cys Ala Ser Leu Thr Lys Lys Arg180 185 190Leu Lys Ser Leu Leu Leu Arg Thr Lys Ala Gly Phe His Trp Val Ile195 200 205Pro Asp Gly Glu Asp Thr Thr Val Arg Ala Ser Thr Asn Cys Thr Tyr210 215 220Asp Arg Ile Val Val His Gly Gln Gly Cys Gln Met Leu Leu Lys Ala225 230 235 240Ala Ala Thr Phe Asp Phe Pro Lys Arg Phe Gln Leu Thr Glu Glu Glu245 250 255Ala Leu Arg Ile Ser Asp His Tyr Pro Val Glu Val Glu Leu Ser Gln260 265 270Ala Thr Pro Leu Ser275<210>41<211>480<212>PRT<213>人(Homo sapiens)<400>41Met Leu Gly Arg Phe Gln Pro Phe Ser Leu Val Arg Ser Phe Arg Leu1 5 10 15Gly Phe Gly Ala Cys Cys Tyr Pro Asn Gln Lys Cys Ala Thr Gln Thr20 25 30Ile Arg Pro Pro Asp Ser Arg Cys Leu Val Gln Ala Val Ser Gln Asn35 40 45Phe Asn Phe Ala Lys Asp Val Leu Asp Gln Trp Ser Gln Leu Glu Lys50 55 60Asp Gly Leu Arg Gly Pro Tyr Pro Ala Leu Trp Lys Val Ser Ala Lys65 70 75 80Gly Glu Glu Asp Lys Trp Ser Phe Glu Arg Met Thr Gln Leu Ser Lys85 90 95Lys Ala Ala Ser Ile Leu Ser Asp Thr Cys Ala Leu Ser His Gly Asp100 105 110Arg Leu Met Ile Ile Leu Pro Pro Thr Pro Glu Ala Tyr Trp Ile Cys115 120 125Leu Ala Cys Val Arg Leu Gly Ile Thr Phe Val Pro Gly Ser Pro Gln130 135 140Leu Thr Ala Lys Lys Ile Arg Tyr Gln Leu Arg Met Ser Lys Ala Gln145 150 155 160Cys Ile Val Ala Asn Glu Ala Met Ala Pro Val Val Asn Ser Ala Val165 170 175Ser Asp Cys Pro Thr Leu Lys Thr Lys Leu Leu Val Ser Asp Lys Ser180 185 190Tyr Asp Gly Trp Leu Asp Phe Lys Lys Leu Ile Gln Val Ala Pro Pro195 200 205Lys Gln Thr Tyr Met Arg Thr Lys Ser Gln Asp Pro Met Ala Ile Phe210 215 220Phe Thr Lys Gly Thr Thr Gly Ala Pro Lys Met Val Glu Tyr Ser Gln225 230 235 240Tyr Gly Leu Gly Met Gly Phe Ser Gln Ala Ser Arg Arg Trp Met Asp245 250 255Leu Gln Pro Thr Asp Val Leu Trp Ser Leu Gly Asp Ala Phe Gly Gly260 265 270Ser Leu Ser Leu Ser Ala Val Leu Gly Thr Trp Phe Gln Gly Ala Cys275 280 285Val Phe Leu Cys His Met Pro Thr Phe Cys Pro Glu Thr Val Leu Asn290 295 300Val Leu Ser Arg Phe Pro Ile Thr Thr Leu Ser Ala Asn Pro Glu Met305 310 315 320Tyr Gln Glu Leu Leu Gln His Lys Cys Phe Thr Ser Tyr Arg Phe Lys325 330 335Ser Leu Lys Gln Cys Val Ala Ala Gly Gly Pro Ile Ser Pro Gly Val340 345 350Ile Glu Asp Trp Lys Arg Ile Thr Lys Leu Asp Ile Tyr Glu Gly Tyr355 360 365Gly Gln Thr Glu Thr Gly Leu Leu Cys Ala Thr Ser Lys Thr Ile Lys370 375 380Leu Lys Pro Ser Ser Leu Gly Lys Pro Leu Pro Pro Tyr Ile Val Gln385 390 395 400Ile Val Asp Glu Asn Ser Asn Leu Leu Pro Pro Gly Glu Glu Gly Asn405 410 415Ile Ala Ile Arg Ile Lys Leu Asn Gln Pro Ala Ser Leu Tyr Cys Pro420 425 430His Met Val Ser Trp Glu Glu Tyr Ala Ser Ala Arg Gly His Met Leu435 440 445Tyr Leu Thr Gly Asp Arg Gly Ile Met Asp Glu Asp Gly Tyr Phe Trp450 455 460Trp Ser Gly Arg Val Asp Asp Val Ala Asn Ala Leu Gly Gln Arg Leu465 470 475 480<210>42<211>583<212>PRT<213>人(Homo sapiens)<400>42Met Leu Gly Arg Phe Gln Pro Phe Ser Leu Val Arg Ser Phe Arg Leu1 5 10 15Gly Phe Gly Ala Cys Cys Tyr Pro Asn Gln Lys Cys Ala Thr Gln Thr20 25 30Ile Arg Pro Pro Asp Ser Arg Cys Leu Val Gln Ala Val Ser Gln Asn35 40 45Phe Asn Phe Ala Lys Asp Val Leu Asp Gln Trp Ser Gln Leu Glu Lys50 55 60Asp Gly Leu Arg Gly Pro Tyr Pro Ala Leu Trp Lys Val Ser Ala Lys65 70 75 80Gly Glu Glu Asp Lys Trp Ser Phe Glu Arg Met Thr Gln Leu Ser Lys85 90 95Lys Ala Ala Ser Ile Leu Ser Asp Thr Cys Ala Leu Ser His Gly Asp100 105 110Arg Leu Met Ile Ile Leu Pro Pro Thr Pro Glu Ala Tyr Trp Ile Cys115 120 125Leu Ala Cys Val Arg Leu Gly Ile Thr Phe Val Pro Gly Ser Pro Gln130 135 140Leu Thr Ala Lys Lys Ile Arg Tyr Gln Leu Arg Met Ser Lys Ala Gln145 150 155 160Cys Ile Val Ala Asn Glu Ala Met Ala Pro Val Val Asn Ser Ala Val165 170 175Ser Asp Cys Pro Thr Leu Lys Thr Lys Leu Leu Val Ser Asp Lys Ser180 185 190Tyr Asp Gly Trp Leu Asp Phe Lys Lys Leu Ile Gln Val Ala Pro Pro195 200 205Lys Gln Thr Tyr Met Arg Thr Lys Ser Gln Asp Pro Met Ala Ile Phe210 215 220Phe Thr Lys Gly Thr Thr Gly Ala Pro Lys Met Val Glu Tyr Ser Gln225 230 235 240Tyr Gly Leu Gly Met Gly Phe Ser Gln Ala Ser Arg Arg Trp Met Asp245 250 255Leu Gln Pro Thr Asp Val Leu Trp Ser Leu Gly Asp Ala Phe Gly Gly260 265 270Ser Leu Ser Leu Ser Ala Val Leu Gly Thr Trp Phe Gln Gly Ala Cys275 280 285Val Phe Leu Cys His Met Pro Thr Phe Cys Pro Glu Thr Val Leu Asn290 295 300Val Leu Ser Arg Phe Pro Ile Thr Thr Leu Ser Ala Asn Pro Glu Met305 310 315 320Tyr Gln Glu Leu Leu Gln His Lys Cys Phe Thr Ser Tyr Arg Phe Lys325 330 335Ser Leu Lys Gln Cys Val Ala Ala Gly Gly Pro Ile Ser Pro Gly Val340 345 350Ile Glu Asp Trp Lys Arg Ile Thr Lys Leu Asp Ile Tyr Glu Gly Tyr355 360 365Gly Gln Thr Glu Thr Gly Leu Leu Cys Ala Thr Ser Lys Thr Ile Lys370 375 380Leu Lys Pro Ser Ser Leu Gly Lys Pro Leu Pro Pro Tyr Ile Val Gln385 390 395 400Ile Val Asp Glu Asn Ser Asn Leu Leu Pro Pro Gly Glu Glu Gly Asn405 410 415Ile Ala Ile Arg Ile Lys Leu Asn Gln Pro Ala Ser Leu Tyr Cys Pro420 425 430His Met Val Ser Trp Glu Glu Tyr Ala Ser Ala Arg Gly His Met Leu435 440 445Tyr Leu Thr Gly Asp Arg Gly Ile Met Asp Glu Asp Gly Tyr Phe Trp450 455 460Trp Ser Gly Arg Val Asp Asp Val Ala Asn Ala Leu Gly Gln Arg Phe465 470 475 480Ser Arg Pro Gly Ala Ala Ala Ala Ala Ser Ala Val Gly Ala Pro Pro485 490 495Gly Gly Trp His Ser Leu Cys Ala Ser Val Pro Ile Leu Gln Val Val500 505 510Lys Pro Pro Asn Val Leu Thr Pro Gln Phe Leu Ser His Asp Gln Gly515 520 525Gln Leu Thr Lys Glu Leu Gln Gln His Ile Lys Ser Val Thr Gly Pro530 535 540Cys Lys Tyr Gln Arg Lys Val Glu Phe Val Pro Glu Leu Pro Lys Thr545 550 555 560Val Thr Gly Lys Ile Lys Arg Glu Leu Gln Val Trp Ser Asp Val Val565 570 575Ser Ser Glu Leu Arg Asn Asp580<210>43<211>581<212>PRT<213>人(Homo sapiens)<400>43Met Pro Leu Lys His Tyr Leu Leu Leu Leu Val Gly Cys Gln Ala Trp1 5 10 15Gly Ala Gly Leu Ala Tyr His Gly Cys Pro Ser Glu Cys Thr Cys Ser20 25 30Arg Ala Ser Gln Val Glu Cys Thr Gly Ala Arg Ile Val Ala Val Pro35 40 45Thr Pro Leu Pro Trp Asn Ala Met Ser Leu Gln Ile Leu Asn Thr His50 55 60Ile Thr Glu Leu Asn Glu Ser Pro Phe Leu Asn Ile Ser Ala Leu Ile65 70 75 80Ala Leu Arg Ile Glu Lys Asn Glu Leu Ser Arg Ile Thr Pro Gly Ala85 90 95Phe Arg Asn Leu Gly Ser Leu Arg Tyr Leu Ser Leu Ala Asn Asn Lys100 105 110Leu Gln Val Leu Pro Ile Gly Leu Phe Gln Gly Leu Asp Ser Leu Glu115 120 125Ser Leu Leu Leu Ser Ser Asn Gln Leu Leu Gln Ile Gln Pro Ala His130 135 140Phe Ser Gln Cys Ser Asn Leu Lys Glu Leu Gln Leu His Gly Asn His145 150 155 160Leu Glu Tyr Ile Pro Asp Gly Ala Phe Asp His Leu Val Gly Leu Thr165 170 175Lys Leu Asn Leu Gly Lys Asn Ser Leu Thr His Ile Ser Pro Arg Val180 185 190Phe Gln His Leu Gly Asn Leu Gln Val Leu Arg Leu Tyr Glu Asn Arg195 200 205Leu Thr Asp Ile Pro Met Gly Thr Phe Asp Gly Leu Val Asn Leu Gln210 215 220Glu Leu Ala Leu Gln Gln Asn Gln Ile Gly Leu Leu Ser Pro Gly Leu225 230 235 240Phe His Asn Asn His Asn Leu Gln Arg Leu Tyr Leu Ser Asn Asn His245 250 255Ile Ser Gln Leu Pro Pro Ser Ile Phe Met Gln Leu Pro Gln Leu Asn260 265 270Arg Leu Thr Leu Phe Gly Asn Ser Leu Lys Glu Leu Ser Leu Gly Ile275 280 285Phe Gly Pro Met Pro Asn Leu Arg Glu Leu Trp Leu Tyr Asp Asn His290 295 300Ile Ser Ser Leu Pro Asp Asn Val Phe Ser Asn Leu Arg Gln Leu Gln305 310 315 320Val Leu Ile Leu Ser Arg Asn Gln Ile Ser Phe Ile Ser Pro Gly Ala325 330 335Phe Asn Gly Leu Thr Glu Leu Arg Glu Leu Ser Leu His Thr Asn Ala340 345 350Leu Gln Asp Leu Asp Gly Asn Val Phe Arg Met Leu Ala Asn Leu Gln355 360 365Asn Ile Ser Leu Gln Asn Asn Arg Leu Arg Gln Leu Pro Gly Asn Ile370 375 380Phe Ala Asn Val Asn Gly Leu Met Ala Ile Gln Leu Gln Asn Asn Gln385 390 395 400Leu Glu Asn Leu Pro Leu Gly Ile Phe Asp His Leu Gly Lys Leu Cys405 410 415Glu Leu Arg Leu Tyr Asp Asn Pro Trp Arg Cys Asp Ser Asp Ile Leu420 425 430Pro Leu Arg Asn Trp Leu Leu Leu Asn Gln Pro Arg Leu Gly Thr Asp435 440 445Thr Val Pro Val Cys Phe Ser Pro Ala Asn Val Arg Gly Gln Ser Leu450 455 460Ile Ile Ile Asn Val Asn Val Ala Val Pro Ser Val His Val Pro Glu465 470 475 480Val Pro Ser Tyr Pro Glu Thr Pro Trp Tyr Pro Asp Thr Pro Ser Tyr485 490 495Pro Asp Thr Thr Ser Val Ser Ser Thr Thr Glu Leu Thr Ser Pro Val500 505 510Glu Asp Tyr Thr Asp Leu Thr Thr Ile Gln Val Thr Asp Asp Arg Ser515 520 525Val Trp Gly Met Thr His Ala His Ser Gly Leu Ala Ile Ala Ala Ile530 535 540Val Ile Gly Ile Val Ala Leu Ala Cys Ser Leu Ala Ala Cys Val Gly545 550 555 560Cys Cys Cys Cys Lys Lys Arg Ser Gln Ala Val Leu Met Gln Met Lys565 570 575Ala Pro Asn Glu Cys580<210>44<211>628<212>PRT<213>人(Homo sapiens)<400>44Met Pro Gly Ala Pro Asp Trp Ser Leu Asn Ser Ser Arg Asn Ala Arg1 5 10 15Ser Leu Glu Gly Leu Pro Leu Cys Pro Trp Trp Ala Leu Phe Val Pro20 25 30Arg Ala Ala Ala Leu Val Gly Leu Gln Arg Lys Gln Glu Asn Ser Ser35 40 45Asp Ile Phe Phe Ser Ser Pro Phe Thr Val Thr Pro Asp Ala Leu Pro50 55 60Thr Ala Ile Thr Trp Glu His Ile Pro Phe Ala Lys Leu Ala Gly Leu65 70 75 80Ile Ala Gly Pro Leu Val Glu Met Cys Arg Gln Arg Leu Ser Lys Glu85 90 95Phe Glu Ala Leu Lys Gly Glu Phe Arg Asp Leu Gly His Cys Leu Pro100 105 110Gly Ala Gln Arg Gly Asn Arg Ile Thr Lys Arg Asn Lys Cys Gly Gln115 120 125Ser Arg Gln Ala Leu Ile Gly Gln Arg Gln Glu Asp Ala Gly Ser Ala130 135 140Pro Leu Gln Met His Pro Ser Val Ala Ala Leu Gly Ala Gly Ala Ala145 150 155 160Leu Arg Glu Ile Gln Pro Leu Gln Arg Glu Pro Glu Leu Ser Ser Gly165 170 175Pro Arg Asn Ser Arg Leu Leu Cys Trp Gly Ser Pro Ala Thr Trp Asn180 185 190Pro Thr Tyr Leu Ser Arg Val Leu Gly Gln Gln Val Ala Val Thr Val195 200 205Thr Glu Ala Gly Leu Gln Ala Val Pro Trp Gly Pro Ser Arg Glu Phe210 215 220Asn Ala Lys Gly Ser Ser Ser Ala Ser Ile Arg Val Gly Gln Pro Gln225 230 235 240Lys Leu Arg Leu Arg Val Gln Arg Ser Arg Arg Gln Cys Pro Pro Val245 250 255Gln Ser Ser Gln Asp Leu Pro Pro Gly Gly Ser Gln Asp Gly Asp Leu260 265 270Lys Glu Pro Thr Glu Arg Val Thr Arg Asp Leu Ser Ser Gly Ala Pro275 280 285Arg Gly Arg Asn Leu Pro Ala Pro Asp Gln Pro Gln Pro Pro Leu Gln290 295 300Arg Gly Thr Arg Leu Arg Leu Arg Gln Arg Arg Arg Arg Leu Leu Ile305 310 315 320Lys Lys Met Pro Ala Ala Ala Thr Ile Pro Ala Asn Ser Ser Asp Ala325 330 335Pro Phe Ile Arg Pro Gly Pro Gly Thr Leu Asp Gly Arg Trp Val Ser340 345 350Leu His Arg Ser Gln Gln Glu Arg Lys Arg Val Met Gln Glu Ala Cys355 360 365Ala Lys Tyr Arg Ala Ser Ser Ser Arg Arg Ala Val Thr Pro Arg His370 375 380Val Ser Arg Ile Phe Val Glu Asp Arg His Arg Val Leu Tyr Cys Glu385 390 395 400Val Pro Lys Ala Gly Cys Ser Asn Trp Lys Arg Val Leu Met Val Leu405 410 415Ala Gly Leu Ala Ser Ser Thr Ala Asp Ile Gln His Asn Thr Val His420 425 430Tyr Gly Ser Ala Leu Lys Arg Leu Asp Thr Phe Asp Arg Gln Gly Ile435 440 445Leu His Arg Leu Ser Thr Tyr Thr Lys Met Leu Phe Val Arg Glu Pro450 455 460Phe Glu Arg Leu Val Ser Ala Phe Arg Asp Lys Phe Glu His Pro Asn465 470 475 480Ser Tyr Tyr His Pro Val Phe Gly Lys Ala Ile Leu Ala Arg Tyr Arg485 490 495Ala Asn Ala Ser Arg Glu Ala Leu Arg Thr Gly Ser Gly Val Arg Phe500 505 510Pro Glu Phe Val Gln Tyr Leu Leu Asp Val His Arg Pro Val Gly Met515 520 525Asp Ile His Trp Asp His Val Ser Arg Leu Cys Ser Pro Cys Leu Ile530 535 540Asp Tyr Asp Phe Val Gly Lys Phe Glu Ser Met Glu Asp Asp Ala Asn545 550 555 560Phe Phe Leu Ser Leu Ile Arg Ala Pro Arg Asn Leu Thr Phe Pro Arg565 570 575Phe Lys Asp Arg His Ser Gln Glu Ala Arg Thr Thr Ala Arg Ile Ala580 585 590His Gln Tyr Phe Ala Gln Leu Ser Ala Leu Gln Arg Gln Arg Thr Tyr
595 600 605Asp Phe Tyr Tyr Met Asp Tyr Leu Met Phe Asn Tyr Ser Lys Pro Phe610 615 620Ala Asp Leu Tyr625<210>45<211>424<212>PRT<213>人(Homo sapiens)<400>45Met Thr Leu Arg Pro Gly Thr Met Arg Leu Ala Cys Met Phe Ser Ser1 5 10 15Ile Leu Leu Phe Gly Ala Ala Gly Leu Leu Leu Phe Ile Ser Leu Gln20 25 30Asp Pro Thr Glu Leu Ala Pro Gln Gln Val Pro Gly Ile Lys Phe Asn35 40 45Ile Arg Pro Arg Gln Pro His His Asp Leu Pro Pro Gly Gly Ser Gln50 55 60Asp Gly Asp Leu Lys Glu Pro Thr Glu Arg Val Thr Arg Asp Leu Ser65 70 75 80Ser Gly Ala Pro Arg Gly Arg Asn Leu Pro Ala Pro Asp Gln Pro Gln85 90 95Pro Pro Leu Gln Arg Gly Thr Arg Leu Arg Leu Arg Gln Arg Arg Arg100 105 110Arg Leu Leu Ile Lys Lys Met Pro Ala Ala Ala Thr Ile Pro Ala Asn115 120 125Ser Ser Asp Ala Pro Phe Ile Arg Pro Gly Pro Gly Thr Leu Asp Gly130 135 140Arg Trp Val Ser Leu His Arg Ser Gln Gln Glu Arg Lys Arg Val Met145 150 155 160Gln Glu Ala Cys Ala Lys Tyr Arg Ala Ser Ser Ser Arg Arg Ala Val165 170 175Thr Pro Arg His Val Ser Arg Ile Phe Val Glu Asp Arg His Arg Val180 185 190Leu Tyr Cys Glu Val Pro Lys Ala Gly Cys Ser Asn Trp Lys Arg Val195 200 205Leu Met Val Leu Ala Gly Leu Ala Ser Ser Thr Ala Asp Ile Gln His210 215 220Asn Thr Val His Tyr Gly Ser Ala Leu Lys Arg Leu Asp Thr Phe Asp225 230 235 240Arg Gln Gly Ile Leu His Arg Leu Ser Thr Tyr Thr Lys Met Leu Phe245 250 255Val Arg Glu Pro Phe Glu Arg Leu Val Ser Ala Phe Arg Asp Lys Phe260 265 270Glu His Pro Asn Ser Tyr Tyr His Pro Val Phe Gly Lys Ala Ile Leu275 280 285Ala Arg Tyr Arg Ala Asn Ala Ser Arg Glu Ala Leu Arg Thr Gly Ser290 295 300Gly Val Arg Phe Pro Glu Phe Val Gln Tyr Leu Leu Asp Val His Arg305 310 315 320Pro Val Gly Met Asp Ile His Trp Asp His Val Ser Arg Leu Cys Ser325 330 335Pro Cys Leu Ile Asp Tyr Asp Phe Val Gly Lys Phe Glu Ser Met Glu340 345 350Asp Asp Ala Asn Phe Phe Leu Ser Leu Ile Arg Ala Pro Arg Asn Leu355 360 365Thr Phe Pro Arg Phe Lys Asp Arg His Ser Gln Glu Ala Arg Thr Thr
370 375 380Ala Arg Ile Ala His Gln Tyr Phe Ala Gln Leu Ser Ala Leu Gln Arg385 390 395 400Gln Arg Thr Tyr Asp Phe Tyr Tyr Met Asp Tyr Leu Met Phe Asn Tyr405 410 415Ser Lys Pro Phe Ala Asp Leu Tyr420<210>46<211>638<212>PRT<213>人(Homo sapiens)<400>46Met Ala Gly Gly Ser Ala Thr Thr Trp Gly Tyr Pro Val Ala Leu Leu1 5 10 15Leu Leu Val Ala Thr Leu Gly Leu Gly Arg Trp Leu Gln Pro Asp Pro20 25 30Gly Leu Pro Gly Leu Arg His Ser Tyr Asp Cys Gly Ile Lys Gly Met35 40 45Gln Leu Leu Val Phe Pro Arg Pro Gly Gln Thr Leu Arg Phe Lys Val50 55 60Val Asp Glu Phe Gly Asn Arg Phe Asp Val Asn Asn Cys Ser Ile Cys65 70 75 80Tyr His Trp Val Thr Ser Arg Pro Gln Glu Pro Ala Val Phe Ser Ala85 90 95Asp Tyr Arg Gly Cys His Val Leu Glu Lys Asp Gly Arg Phe His Leu100 105 110Arg Val Phe Met Glu Ala Val Leu Pro Asn Gly Arg Val Asp Val Ala115 120 125Gln Asp Ala Thr Leu Ile Cys Pro Lys Pro Asp Pro Ser Arg Thr Leu130 135 140Asp Ser Gln Leu Ala Pro Pro Ala Met Phe Ser Val Ser Thr Pro Gln145 150 155 160Thr Leu Ser Phe Leu Pro Thr Ser Gly His Thr Ser Gln Gly Ser Gly165 170 175His Ala Phe Pro Ser Pro Leu Asp Pro Gly His Ser Ser Val His Pro180 185 190Thr Pro Ala Leu Pro Ser Pro Gly Pro Gly Pro Thr Leu Ala Thr Leu195 200 205Ala Gln Pro His Trp Gly Thr Leu Glu His Trp Asp Val Asn Lys Arg210 215 220Asp Tyr Ile Gly Thr His Leu Ser Gln Glu Gln Cys Gln Val Ala Ser225 230 235 240Gly His Leu Pro Cys Ile Val Arg Arg Thr Ser Lys Glu Ala Cys Gln245 250 255Gln Ala Gly Cys Cys Tyr Asp Asn Thr Arg Glu Val Pro Cys Tyr Tyr260 265 270Gly Asn Thr Ala Thr Val Gln Cys Phe Arg Asp Gly Tyr Phe Val Leu275 280 285Val Val Ser Gln Glu Met Ala Leu Thr His Arg Ile Thr Leu Ala Asn290 295 300Ile His Leu Ala Tyr Ala Pro Thr Ser Cys Ser Pro Thr Gln His Thr305 310 315 320Glu Ala Phe Val Val Phe Tyr Phe Pro Leu Thr His Cys Gly Thr Thr325 330 335Met Gln Val Ala Gly Asp Gln Leu Ile Tyr Glu Asn Trp Leu Val Ser340 345 350Gly Ile His Ile Gln Lys Gly Pro Gln Gly Ser Ile Thr Arg Asp Ser
355 360 365Thr Phe Gln Leu His Val Arg Cys Val Phe Asn Ala Ser Asp Phe Leu370 375 380Pro Ile Gln Ala Ser Ile Phe Pro Pro Pro Ser Pro Ala Pro Met Thr385 390 395 400Gln Pro Gly Pro Leu Arg Leu Glu Leu Arg Ile Ala Lys Asp Glu Thr405 410 415Phe Ser Ser Tyr Tyr Gly Glu Asp Asp Tyr Pro Ile Val Arg Leu Leu420 425 430Arg Glu Pro Val His Val Glu Val Arg Leu Leu Gln Arg Thr Asp Pro435 440 445Asn Leu Val Leu Leu Leu His Gln Cys Trp Gly Ala Pro Ser Ala Asn450 455 460Pro Phe Gln Gln Pro Gln Trp Pro Ile Leu Ser Asp Gly Cys Pro Phe465 470 475 480Lys Gly Asp Ser Tyr Arg Thr Gln Met Val Ala Leu Asp Gly Ala Thr485 490 495Pro Phe Gln Ser His Tyr Gln Arg Phe Thr Val Ala Thr Phe Ala Leu500 505 510Leu Asp Ser Gly Ser Gln Arg Ala Leu Arg Gly Leu Val Tyr Leu Phe515 520 525Cys Ser Thr Ser Ala Cys His Thr Ser Gly Leu Glu Thr Cys Ser Thr530 535 540Ala Cys Ser Thr Gly Thr Thr Arg Gln Arg Arg Ser Ser Gly His Arg545 550 555 560Asn Asp Thr Ala Arg Pro Gln Asp Ile Val Ser Ser Pro Gly Pro Val565 570 575Gly Phe Glu Asp Ser Tyr Gly Gln Glu Pro Thr Leu Gly Pro Thr Asp580 585 590Ser Asn Gly Asn Ser Ser Leu Arg Pro Leu Leu Trp Ala Val Leu Leu595 600 605Leu Pro Ala Val Ala Leu Val Leu Gly Phe Gly Val Phe Val Gly Leu610 615 620Ser Gln Thr Trp Ala Gln Lys Leu Trp Glu Ser Asn Arg Gln625 630 635<210>47<211>229<212>PRT<213>人(Homo sapiens)<400>47Met Lys Pro Leu Ala Gln Leu Leu Leu Phe Leu Leu Gln Phe Gln Lys1 5 10 15Gly Asn Leu Val Ser Gln Ser Ser Ser Thr Pro Leu Met Val Asn Gly20 25 30Val Leu Gly Glu Ser Val Thr Leu Pro Leu Glu Phe Pro Ala Gly Glu35 40 45Arg Ile Gln Phe Ile Thr Trp Leu Cys Asn Gly Thr Ser Phe Ala Phe50 55 60Leu Glu Pro Tyr Glu Gly Lys Ser Pro Lys Ile Tyr Val Thr His Pro65 70 75 80Lys Trp Gln Lys Arg Leu Ser Phe Thr Gln Ser Tyr Ser Pro Gln Leu85 90 95Ser Asn Leu Glu Met Glu Asn Ile Gly Phe Tyr Ser Ala Gln Ile Ala100 105 110Thr Glu Thr Ser Ala Lys Leu Ser Ser Tyr Thr Leu Arg Ile Phe Lys115 120 125Gln Leu Pro Arg Pro Gln Val Arg Val Asp Ser Ile Ile Ser Glu Asn
130 135 140Gly Ile Cys Asn Ala Ile Leu Arg Cys Ser Val Glu Glu Gly Gly Glu145 150 155 160Thr Ile Thr Tyr Glu Trp Thr Ser Met Gly Pro Gly Ala Ala Val Ser165 170 175His Val Gly Leu His Asp Leu Asp Trp Ile Tyr Thr Cys Thr Ala Leu180 185 190Asn Pro Val Ser Tyr Ser Asn Ser Thr Leu Thr Leu Ala Ala Gln Leu195 200 205Cys Ala Ser Lys Ser Pro Leu Leu Val Ser Leu Ala Pro Leu Gly Asn210 215 220Val Leu Ser Gly Leu225<210>48<211>310<212>PRT<213>人(Homo sapiens)<400>48Met Lys Pro Leu Ala Gln Leu Leu Leu Phe Leu Leu Gln Phe Gln Lys1 5 10 15Gly Asn Leu Val Ser Gln Ser Ser Ser Thr Pro Leu Met Val Asn Gly20 25 30Val Leu Gly Glu Ser Val Thr Leu Pro Leu Glu Phe Pro Ala Gly Glu35 40 45Arg Ile Gln Phe Ile Thr Trp Leu Cys Asn Gly Thr Ser Phe Ala Phe50 55 60Leu Glu Pro Tyr Glu Gly Lys Ser Pro Lys Ile Tyr Val Thr His Pro65 70 75 80Lys Trp Gln Lys Arg Leu Ser Phe Thr Gln Ser Tyr Ser Pro Gln Leu85 90 95Ser Asn Leu Glu Met Glu Asn Ile Gly Phe Tyr Ser Ala Gln Ile Ala100 105 110Thr Glu Thr Ser Ala Lys Leu Ser Ser Tyr Thr Leu Arg Ile Phe Lys115 120 125Gln Leu Pro Arg Pro Gln Val Arg Val Asp Ser Ile Ile Ser Glu Asn130 135 140Gly Ile Cys Asn Ala Ile Leu Arg Cys Ser Val Glu Glu Gly Gly Glu145 150 155 160Thr Ile Thr Tyr Glu Trp Thr Ser Met Gly Pro Gly Ala Ala Val Ser165 170 175His Val Gly Leu His Asp Leu Asp Trp Ile Tyr Thr Cys Thr Ala Leu180 185 190Asn Pro Val Ser Tyr Ser Asn Ser Thr Leu Thr Leu Ala Ala Gln Leu195 200 205Cys Ala Ser Ser Lys Ala Ala Glu Gly Thr Tyr Cys Pro Val Lys Trp210 215 220Ile Phe Leu Gly Asn Arg Leu Leu Leu Leu Val Phe Leu Gly Val Leu225 230 235 240Arg Thr Trp His Ile Gln Ala Gln Val Leu Ser Lys Pro Leu Arg Pro245 250 255Asn Ser Gly Glu Leu Val Asn Leu Ser Ser Ile Pro Tyr Pro Trp Glu260 265 270Pro Ser His Thr Ala Asp Ala Thr Trp Leu Gly Lys Trp Gly Gly Ser275 280 285Glu Gly Glu Arg Lys Ser Thr Trp Asn Ile Ser Thr Thr Lys Arg His290 295 300Trp Lys Ser Phe Tyr Lys305 310<210>49<211>841<212>PRT<213>人(Homo sapiens)<400>49Met Lys Leu Trp Ile His Leu Phe Tyr Ser Ser Leu Leu Ala Cys Ile1 5 10 15Ser Leu His Ser Gln Thr Pro Val Leu Ser Ser Arg Gly Ser Cys Asp20 25 30Ser Leu Cys Asn Cys Glu Glu Lys Asp Gly Thr Met Leu Ile Asn Cys35 40 45Glu Ala Lys Gly Ile Lys Met Val Ser Glu Ile Ser Val Pro Pro Ser50 55 60Arg Pro Phe Gln Leu Ser Leu Leu Asn Asn Gly Leu Thr Met Leu His65 70 75 80Thr Asn Asp Phe Ser Gly Leu Thr Asn Ala Ile Ser Ile His Leu Gly85 90 95Phe Asn Asn Ile Ala Asp Ile Glu Ile Gly Ala Phe Asn Gly Leu Gly100 105 110Leu Leu Lys Gln Leu His Ile Asn His Asn Ser Leu Glu Ile Leu Lys115 120 125Glu Asp Thr Phe His Gly Leu Glu Asn Leu Glu Phe Leu Gln Ala Asp130 135 140Asn Asn Phe Ile Thr Val Ile Glu Pro Ser Ala Phe Ser Lys Leu Asn145 150 155 160Arg Leu Lys Val Leu Ile Leu Asn Asp Asn Ala Ile Glu Ser Leu Pro165 170 175Pro Asn Ile Phe Arg Phe Val Pro Leu Thr His Leu Asp Leu Arg Gly180 185 190Asn Gln Leu Gln Thr Leu Pro Tyr Val Gly Phe Leu Glu His Ile Gly195 200 205Arg Ile Leu Asp Leu Gln Leu Glu Asp Asn Lys Trp Ala Cys Asn Cys210 215 220Asp Leu Leu Gln Leu Lys Thr Trp Leu Glu Asn Met Pro Pro Gln Ser225 230 235 240Ile Ile Gly Asp Val Val Cys Asn Ser Pro Pro Phe Phe Lys Gly Ser245 250 255Ile Leu Ser Arg Leu Lys Lys Glu Ser Ile Cys Pro Thr Pro Pro Val260 265 270Tyr Glu Glu His Glu Asp Pro Ser Gly Ser Leu His Leu Ala Ala Thr275 280 285Ser Ser Ile Asn Asp Ser Arg Met Ser Thr Lys Thr Thr Ser Ile Leu290 295 300Lys Leu Pro Thr Lys Ala Pro Gly Leu Ile Pro Tyr Ile Thr Lys Pro305 310 315 320Ser Thr Gln Leu Pro Gly Pro Tyr Cys Pro Ile Pro Cys Asn Cys Lys325 330 335Val Leu Ser Pro Ser Gly Leu Leu Ile His Cys Gln Glu Arg Asn Ile340 345 350Glu Ser Leu Ser Asp Leu Arg Pro Pro Pro Gln Asn Pro Arg Lys Leu355 360 365Ile Leu Ala Gly Asn Ile Ile His Ser Leu Met Lys Ser Asp Leu Val370 375 380Glu Tyr Phe Thr Leu Glu Met Leu His Leu Gly Asn Asn Arg Ile Glu385 390 395 400Val Leu Glu Glu Gly Ser Phe Met Asn Leu Thr Arg Leu Gln Lys Leu
405 410 415Tyr Leu Asn Gly Asn His Leu Thr Lys Leu Ser Lys Gly Met Phe Leu420 425 430Gly Leu His Asn Leu Glu Tyr Leu Tyr Leu Glu Tyr Asn Ala Ile Lys435 440 445Glu Ile Leu Pro Gly Thr Phe Asn Pro Met Pro Lys Leu Lys Val Leu450 455 460Tyr Leu Asn Asn Asn Leu Leu Gln Val Leu Pro Pro His Ile Phe Ser465 470 475 480Gly Val Pro Leu Thr Lys Val Asn Leu Lys Thr Asn Gln Phe Thr His485 490 495Leu Pro Val Ser Asn Ile Leu Asp Asp Leu Asp Leu Leu Thr Gln Ile500 505 510Asp Leu Glu Asp Asn Pro Trp Asp Cys Ser Cys Asp Leu Val Gly Leu515 520 525Gln Gln Trp Ile Gln Lys Leu Ser Lys Asn Thr Val Thr Asp Asp Ile530 535 540Leu Cys Thr Ser Pro Gly His Leu Asp Lys Lys Glu Leu Lys Ala Leu545 550 555 560Asn Ser Glu Ile Leu Cys Pro Gly Leu Val Asn Asn Pro Ser Met Pro565 570 575Thr Gln Thr Ser Tyr Leu Met Val Thr Thr Pro Ala Thr Thr Thr Asn580 585 590Thr Ala Asp Thr Ile Leu Arg Ser Leu Thr Asp Ala Val Pro Leu Ser595 600 605Val Leu Ile Leu Gly Leu Leu Ile Met Phe Ile Thr Ile Val Phe Cys610 615 620Ala Ala Gly Ile Val Val Leu Val Leu His Arg Arg Arg Arg Tyr Lys625 630 635 640Lys Lys Gln Val Asp Glu Gln Met Arg Asp Asn Ser Pro Val His Leu645 650 655Gln Tyr Ser Met Tyr Gly His Lys Thr Thr His His Thr Thr Glu Arg660 665 670Pro Ser Ala Ser Leu Tyr Glu Gln His Met Val Ser Pro Met Val His675 680 685Val Tyr Arg Ser Pro Ser Phe Gly Pro Lys His Leu Glu Glu Glu Glu690 695 700Glu Arg Asn Glu Lys Glu Gly Ser Asp Ala Lys His Leu Gln Arg Ser705 710 715 720Leu Leu Glu Gln Glu Asn His Ser Pro Leu Thr Gly Ser Asn Met Lys725 730 735Tyr Lys Thr Thr Asn Gln Ser Thr Glu Phe Leu Ser Phe Gln Asp Ala740 745 750Ser Ser Leu Tyr Arg Asn Ile Leu Glu Lys Glu Arg Glu Leu Gln Gln755 760 765Leu Gly Ile Thr Glu Tyr Leu Arg Lys Asn Ile Ala Gln Leu Gln Pro770 775 780Asp Met Glu Ala His Tyr Pro Gly Ala His Glu Glu Leu Lys Leu Met785 790 795 800Glu Thr Leu Met Tyr Ser Arg Pro Arg Lys Val Leu Val Glu Gln Thr805 810 815Lys Asn Glu Tyr Phe Glu Leu Lys Ala Asn Leu His Ala Glu Pro Asp820 825 830Tyr Leu Glu Val Leu Glu Gln Gln Thr835 840<210>50<211>241<212>PRT
<213>人(Homo sapiens)<400>50Met Gly Asn Pro Gly Leu Ala Trp Leu Val Leu Leu Gly Leu Val Leu1 5 10 15Leu Leu Ser Ser Phe Met Glu Arg Gly Gly His Ser Pro Ser Pro Ala20 25 30Ala Leu Ser Ala Met Glu Asn Leu Ile Thr Tyr Ala Val Gln Lys Gly35 40 45His Leu Ser Ser Ser Tyr Val Gln Pro Leu Leu Val Lys Gly Glu Asn50 55 60Cys Leu Ala Pro Arg Gln Lys Thr Ser Leu Lys Lys Ala Cys Pro Gly65 70 75 80Val Val Pro Arg Ser Val Trp Gly Ala Arg Glu Thr His Cys Pro Arg85 90 95Met Thr Leu Pro Ala Lys Tyr Gly Ile Ile Ile His Thr Ala Gly Arg100 105 110Thr Cys Asn Ile Ser Asp Glu Cys Arg Leu Leu Val Arg Asp Ile Gln115 120 125Ser Phe Tyr Ile Asp Arg Leu Lys Ser Cys Asp Ile Gly Tyr Asn Phe130 135 140Leu Val Gly Gln Asp Gly Ala Ile Tyr Glu Gly Val Gly Trp Asn Val145 150 155 160Gln Gly Ser Ser Thr Pro Gly Tyr Asp Asp Ile Ala Leu Gly Ile Thr165 170 175Phe Met Gly Thr Phe Thr Gly Ile Pro Pro Asn Ala Ala Ala Leu Glu180 185 190Ala Ala Gln Asp Leu Ile Gln Cys Ala Met Val Lys Gly Tyr Leu Thr195 200 205Pro Asn Tyr Leu Leu Val Gly His Ser Asp Val Ala Arg Thr Leu Ser210 215 220Pro Gly Gln Ala Leu Tyr Asn Ile Ile Ser Thr Trp Pro His Phe Lys225 230 235 240His<210>51<211>369<212>PRT<213>人(Homo sapiens)<400>51Met Leu Pro Trp Leu Leu Val Phe Ser Ala Leu Gly Leu Gln Ala Trp1 5 10 15Gly Asp Ser Ser Trp Asn Lys Thr Gln Ala Lys Gln Val Ser Glu Gly20 25 30Leu Gln Tyr Leu Phe Glu Asn Ile Ser Gln Leu Thr Glu Lys Asp Val35 40 45Ser Thr Thr Val Ser Arg Lys Ala Trp Gly Ala Glu Ala Val Gly Cys50 55 60Ser Ile Gln Leu Thr Thr Pro Val Asn Val Leu Val Ile His His Val65 70 75 80Pro Gly Leu Glu Cys His Asp Arg Thr Val Cys Ser Gln Arg Leu Arg85 90 95Glu Leu Gln Ala His His Val His Asn Asn Ser Gly Cys Asp Val Ala100 105 110Tyr Asn Phe Leu Val Gly Asp Asp Gly Arg Val Tyr Glu Gly Val Gly115 120 125Trp Asn Ile Gln Gly Val His Thr Gln Gly Tyr Asn Asn Ile Ser Leu
130 135 140Gly Phe Ala Phe Phe Gly Thr Lys Lys Gly His Ser Pro Ser Pro Ala145 150 155 160Ala Leu Ser Ala Met Glu Asn Leu Ile Thr Tyr Ala Val Gln Lys Gly165 170 175His Leu Ser Ser Ser Tyr Val Gln Pro Leu Leu Val Lys Gly Glu Asn180 185 190Cys Leu Ala Pro Arg Gln Lys Thr Ser Leu Lys Lys Ala Cys Pro Gly195 200 205Val Val Pro Arg Ser Val Trp Gly Ala Arg Glu Thr His Cys Pro Arg210 215 220Met Thr Leu Pro Ala Lys Tyr Gly Ile Ile Ile His Thr Ala Gly Arg225 230 235 240Thr Cys Asn Ile Ser Asp Glu Cys Arg Leu Leu Val Arg Asp Ile Gln245 250 255Ser Phe Tyr Ile Asp Arg Leu Lys Ser Cys Asp Ile Gly Tyr Asn Phe260 265 270Leu Val Gly Gln Asp Gly Ala Ile Tyr Glu Gly Val Gly Trp Asn Val275 280 285Gln Gly Ser Ser Thr Pro Gly Tyr Asp Asp Ile Ala Leu Gly Ile Thr290 295 300Phe Met Gly Thr Phe Thr Gly Ile Pro Pro Asn Ala Ala Ala Leu Glu305 310 315 320Ala Ala Gln Asp Leu Ile Gln Cys Ala Met Val Lys Gly Tyr Leu Thr325 330 335Pro Asn Tyr Leu Leu Val Gly His Ser Asp Val Ala Arg Thr Leu Ser340 345 350Pro Gly Gln Ala Leu Tyr Asn Ile Ile Ser Thr Trp Pro His Phe Lys355 360 365His<210>52<211>382<212>PRT<213>人(Homo sapiens)<400>52Met Ala Pro Arg Ala Gly Gln Pro Gly Leu Gln Gly Leu Leu Leu Val1 5 10 15Ala Ala Ala Leu Ser Gln Pro Ala Ala Pro Cys Pro Phe Gln Cys Tyr20 25 30Cys Phe Gly Gly Pro Lys Leu Leu Leu Arg Cys Ala Ser Gly Ala Glu35 40 45Leu Arg Gln Pro Pro Arg Asp Val Pro Pro Asp Ala Arg Asn Leu Thr50 55 60Ile Val Gly Ala Asn Leu Thr Val Leu Arg Ala Ala Ala Phe Ala Gly65 70 75 80Gly Asp Gly Asp Gly Asp Gln Ala Ala Gly Val Arg Leu Pro Leu Leu85 90 95Ser Ala Leu Arg Leu Thr His Asn His Ile Glu Val Val Glu Asp Gly100 105 110Ala Phe Asp Gly Leu Pro Ser Leu Ala Ala Leu Asp Leu Ser His Asn115 120 125Pro Leu Arg Ala Leu Gly Gly Gly Ala Phe Arg Gly Leu Pro Ala Leu130 135 140Arg Ser Leu Gln Leu Asn His Ala Leu Val Arg Gly Gly Pro Ala Leu145 150 155 160Leu Ala Ala Leu Asp Ala Ala Leu Ala Pro Leu Ala Glu Leu Arg Leu165 170 175Leu Gly Leu Ala Gly Asn Ala Leu Ser Arg Leu Pro Pro Ala Ala Leu180 185 190Arg Leu Ala Arg Leu Glu Gln Leu Asp Val Arg Leu Asn Ala Leu Ala195 200 205Gly Leu Asp Pro Asp Glu Leu Arg Ala Leu Glu Arg Asp Gly Gly Leu210 215 220Pro Gly Pro Arg Leu Leu Leu Ala Asp Asn Pro Leu Arg Cys Gly Cys225 230 235 240Ala Ala Arg Pro Leu Leu Ala Trp Leu Arg Asn Ala Thr Glu Arg Val245 250 255Pro Asp Ser Arg Arg Leu Arg Cys Ala Ala Pro Arg Ala Leu Leu Asp260 265 270Arg Pro Leu Leu Asp Leu Asp Gly Ala Arg Leu Arg Cys Ala Asp Ser275 280 285Gly Ala Asp Ala Arg Gly Glu Glu Ala Glu Ala Ala Gly Pro Glu Leu290 295 300Glu Ala Ser Tyr Val Phe Phe Gly Leu Val Leu Ala Leu Ile Gly Leu305 310 315 320Ile Phe Leu Met Val Leu Tyr Leu Asn Arg Arg Gly Ile Gln Arg Trp325 330 335Met Arg Asn Leu Arg Glu Ala Cys Arg Asp Gln Met Glu Gly Tyr His340 345 350Tyr Arg Tyr Glu Gln Asp Ala Asp Pro Arg Arg Ala Pro Ala Pro Ala355 360 365Ala Pro Ala Gly Ser Arg Ala Thr Ser Pro Gly Ser Gly Leu370 375 380<210>53<211>185<212>PRT<213>人(Homo sapiens)<400>53Met Met Leu Leu Leu Leu Cys Leu Gly Leu Thr Leu Val Cys Ala Gln1 5 10 15Glu Glu Glu Asn Asn Asp Ala Val Thr Ser Asn Phe Asp Leu Ser Lys20 25 30Ile Ser Gly Glu Trp Tyr Ser Val Leu Leu Ala Ser Asp Cys Arg Glu35 40 45Lys Ile Glu Glu Asp Gly Ser Met Arg Val Phe Val Lys His Ile Asp50 55 60Tyr Leu Gly Asn Ser Ser Leu Thr Phe Lys Leu His Glu Ile Glu Asn65 70 75 80Gly Asn Cys Thr Glu Ile Asn Leu Ala Cys Lys Pro Thr Glu Lys Asn85 90 95Ala Ile Cys Ser Thr Asp Tyr Asn Gly Leu Asn Val Ile Asp Ile Leu100 105 110Glu Thr Asp Tyr Asp Asn Tyr Ile Tyr Phe Tyr Asn Lys Asn Ile Lys115 120 125Asn Gly Glu Thr Phe Leu Met Leu Glu Leu Tyr Val Arg Thr Pro Asp130 135 140Val Ser Ser Gln Leu Lys Glu Arg Phe Val Lys Tyr Cys Glu Glu His145 150 155 160Gly Ile Asp Lys Glu Asn Ile Phe Asp Leu Thr Lys Val Asp Arg Cys165 170 175Leu Gln Ala Arg Asp Glu Gly Ala Ala180 185<210>54
<211>586<212>PRT<213>人(Homo sapiens)<400>54Met His Tyr Asn Leu Gln Gly Pro Thr Arg Arg Ile Arg Ile Ser Leu1 5 10 15Leu Asn Asp Gly Gly Leu Lys Ile Ala Asn Val Thr Lys Ala Asp Ala20 25 30Gly Thr Tyr Thr Cys Met Ala Glu Asn Gln Phe Gly Lys Ala Asn Gly35 40 45Thr Thr His Leu Val Val Thr Glu Pro Thr Arg Ile Thr Leu Ala Pro50 55 60Ser Asn Met Asp Val Ser Val Gly Glu Ser Val Ile Leu Pro Cys Gln65 70 75 80Val Gln His Asp Pro Leu Leu Asp Ile Ile Phe Thr Trp Tyr Phe Asn85 90 95Gly Ala Leu Ala Asp Phe Lys Lys Asp Gly Ser His Phe Glu Lys Val100 105 110Gly Gly Ser Ser Ser Gly Asp Leu Met Ile Arg Asn Ile Gln Leu Lys115 120 125His Ser Gly Lys Tyr Val Cys Met Val Gln Thr Gly Val Asp Ser Val130 135 140Ser Ser Ala Ala Asp Leu Ile Val Arg Gly Ser Pro Gly Pro Pro Glu145 150 155 160Asn Val Lys Val Asp Glu Ile Thr Asp Thr Thr Ala Gln Leu Ser Trp165 170 175Lys Glu Gly Lys Asp Asn His Ser Pro Val Ile Ser Tyr Ser Ile Gln180 185 190Ala Arg Thr Pro Phe Ser Val Gly Trp Gln Thr Val Thr Thr Val Pro195 200 205Glu Val Ile Asp Gly Lys Thr His Thr Ala Thr Val Val Glu Leu Asn210 215 220Pro Trp Val Glu Tyr Glu Phe Arg Val Val Ala Ser Asn Lys Ile Gly225 230 235 240Gly Gly Glu Pro Ser Leu Pro Ser Glu Lys Val Arg Thr Glu Glu Ala245 250 255Val Pro Glu Val Pro Pro Ser Glu Val Asn Gly Gly Gly Gly Ser Arg260 265 270Ser Glu Leu Val Ile Thr Trp Asp Pro Val Pro Glu Glu Leu Gln Asn275 280 285Gly Glu Gly Phe Gly Tyr Val Val Ala Phe Arg Pro Leu Gly Val Thr290 295 300Thr Trp Ile Gln Thr Val Val Thr Ser Pro Asp Thr Pro Arg Tyr Val305 310 315 320Phe Arg Asn Glu Ser Ile Val Pro Tyr Ser Pro Tyr Glu Val Lys Val325 330 335Gly Val Tyr Asn Asn Lys Gly Glu Gly Pro Phe Ser Pro Val Thr Thr340 345 350Val Phe Ser Ala Glu Glu Glu Pro Thr Val Ala Pro Ser Gln Val Ser355 360 365Ala Asn Ser Leu Ser Ser Ser Glu Ile Glu Val Ser Trp Asn Thr Ile370 375 380Pro Trp Lys Leu Ser Asn Gly His Leu Leu Gly Tyr Glu Val Arg Tyr385 390 395 400Trp Asn Gly Gly Gly Lys Glu Glu Ser Ser Ser Lys Met Lys Val Ala405 410 415Gly Asn Glu Thr Ser Ala Arg Leu Arg Gly Leu Lys Ser Asn Leu Ala420 425 430Tyr Tyr Thr Ala Val Arg Ala Tyr Asn Ser Ala Gly Ala Gly Pro Phe435 440 445Ser Ala Thr Val Asn Val Thr Thr Lys Lys Thr Pro Pro Ser Gln Pro450 455 460Pro Gly Asn Val Val Trp Asn Ala Thr Asp Thr Lys Val Leu Leu Asn465 470 475 480Trp Glu Gln Val Lys Ala Met Glu Asn Glu Ser Glu Val Thr Gly Tyr485 490 495Lys Val Phe Tyr Arg Thr Ser Ser Gln Asn Asn Val Gln Val Leu Asn500 505 510Thr Asn Lys Thr Ser Ala Glu Leu Val Leu Pro Ile Lys Glu Asp Tyr515 520 525Ile Ile Glu Val Lys Ala Thr Thr Asp Gly Gly Asp Gly Thr Ser Ser530 535 540Glu Gln Ile Arg Ile Pro Arg Ile Thr Ser Met Asp Ala Arg Gly Ser545 550 555 560Thr Ser Ala Ile Ser Asn Val His Pro Met Ser Ser Tyr Met Pro Ile565 570 575Val Leu Phe Leu Ile Val Tyr Val Leu Trp580 585<210>55<211>1026<212>PRT<213>人(Homo sapiens)<400>55Met Leu Val Val Glu Arg Val Met Val Leu Pro Ile Gly Phe Pro Leu1 5 10 15Gly Val Ser Asp Asp Ser Thr Leu His Gly Pro Ile Phe Ile Gln Glu20 25 30Pro Ser Pro Val Met Phe Pro Leu Asp Ser Glu Glu Lys Lys Val Lys35 40 45Leu Asn Cys Glu Val Lys Gly Asn Pro Lys Pro His Ile Arg Trp Lys50 55 60Leu Asn Gly Thr Asp Val Asp Thr Gly Met Asp Phe Arg Tyr Ser Val65 70 75 80Val Glu Gly Ser Leu Leu Ile Asn Asn Pro Asn Lys Thr Gln Asp Ala85 90 95Gly Thr Tyr Gln Cys Thr Ala Thr Asn Ser Phe Gly Thr Ile Val Ser100 105 110Arg Glu Ala Lys Leu Gln Phe Ala Tyr Leu Asp Asn Phe Lys Thr Arg115 120 125Thr Arg Ser Thr Val Ser Val Arg Arg Gly Gln Gly Met Val Leu Leu130 135 140Cys Gly Pro Pro Pro His Ser Gly Glu Leu Ser Tyr Ala Trp Ile Phe145 150 155 160Asn Glu Tyr Pro Ser Tyr Gln Asp Asn Arg Arg Phe Val Ser Gln Glu165 170 175Thr Gly Asn Leu Tyr Ile Ala Lys Val Glu Lys Ser Asp Val Gly Asn180 185 190Tyr Thr Cys Val Val Thr Asn Thr Val Thr Asn His Lys Val Leu Gly195 200 205Pro Pro Thr Pro Leu Ile Leu Arg Asn Asp Gly Val Met Gly Glu Tyr210 215 220Glu Pro Lys Ile Glu Val Gln Phe Pro Glu Thr Val Pro Thr Ala Lys225 230 235 240Gly Ala Thr Val Lys Leu Glu Cys Phe Ala Leu Gly Asn Pro Val Pro245 250 255Thr Ile Ile Trp Arg Arg Ala Asp Gly Lys Pro Ile Ala Arg Lys Ala260 265 270Arg Arg His Lys Ser Asn Gly Ile Leu Glu Ile Pro Asn Phe Gln Gln275 280 285Glu Asp Ala Gly Leu Tyr Glu Cys Val Ala Glu Asn Ser Arg Gly Lys290 295 300Asn Val Ala Arg Gly Gln Leu Thr Phe Tyr Ala Gln Pro Asn Trp Ile305 310 315 320Gln Lys Ile Asn Asp Ile His Val Ala Met Glu Glu Asn Val Phe Trp325 330 335Glu Cys Lys Ala Asn Gly Arg Pro Lys Pro Thr Tyr Lys Trp Leu Lys340 345 350Asn Gly Glu Pro Leu Leu Thr Arg Asp Arg Ile Gln Ile Glu Gln Gly355 360 365Thr Leu Asn Ile Thr Ile Val Asn Leu Ser Asp Ala Gly Met Tyr Gln370 375 380Cys Leu Ala Glu Asn Lys His Gly Val Ile Phe Ser Asn Ala Glu Leu385 390 395 400Ser Val Ile Ala Val Gly Pro Asp Phe Ser Arg Thr Leu Leu Lys Arg405 410 415Val Thr Leu Val Lys Val Gly Gly Glu Val Val Ile Glu Cys Lys Pro420 425 430Lys Ala Ser Pro Lys Pro Val Tyr Thr Trp Lys Lys Gly Arg Asp Ile435 440 445Leu Lys Glu Asn Glu Arg Ile Thr Ile Ser Glu Asp Gly Asn Leu Arg450 455 460Ile Ile Asn Val Thr Lys Ser Asp Ala Gly Ser Tyr Thr Cys Ile Ala465 470 475 480Thr Asn His Phe Gly Thr Ala Ser Ser Thr Gly Asn Leu Val Val Lys485 490 495Asp Pro Thr Arg Val Met Val Pro Pro Ser Ser Met Asp Val Thr Val500 505 510Gly Glu Ser Ile Val Leu Pro Cys Gln Val Thr His Asp His Ser Leu515 520 525Asp Ile Val Phe Thr Trp Ser Phe Asn Gly His Leu Ile Asp Phe Asp530 535 540Arg Asp Gly Asp His Phe Glu Arg Val Gly Gly Asp Ser Ala Gly Asp545 550 555 560Leu Met Ile Arg Asn Ile Gln Leu Lys His Ala Gly Lys Tyr Val Cys565 570 575Met Val Gln Thr Ser Val Asp Arg Leu Ser Ala Ala Ala Asp Leu Ile580 585 590Val Arg Gly Pro Pro Gly Pro Pro Glu Ala Val Thr Ile Asp Glu Ile595 600 605Thr Asp Thr Thr Ala Gln Leu Ser Trp Arg Pro Gly Pro Asp Asn His610 615 620Ser Pro Ile Thr Met Tyr Val Ile Gln Ala Arg Thr Pro Phe Ser Val625 630 635 640Gly Trp Gln Ala Val Ser Thr Val Pro Glu Leu Ile Asp Gly Lys Thr645 650 655Phe Thr Ala Thr Val Val Gly Leu Asn Pro Trp Val Glu Tyr Glu Phe660 665 670Arg Thr Val Ala Ala Asn Val Ile Gly Ile Gly Glu Pro Ser Arg Pro675 680 685Ser Glu Lys Arg Arg Thr Glu Glu Ala Leu Pro Glu Val Thr Pro Ala690 695 700Asn Val Ser Gly Gly Gly Gly Ser Lys Ser Glu Leu Val Ile Thr Trp705 710 715 720Glu Thr Val Pro Glu Glu Leu Gln Asn Gly Arg Gly Phe Gly Tyr Val
725 730 735Val Ala Phe Arg Pro Tyr Gly Lys Met Ile Trp Met Leu Thr Val Leu740 745 750Ala Ser Ala Asp Ala Ser Arg Tyr Val Phe Arg Asn Glu Ser Val His755 760 765Pro Phe Ser Pro Phe Glu Val Lys Val Gly Val Phe Asn Asn Lys Gly770 775 780Glu Gly Pro Phe Ser Pro Thr Thr Val Val Tyr Ser Ala Glu Glu Glu785 790 795 800Pro Thr Lys Pro Pro Ala Ser Ile Phe Ala Arg Ser Leu Ser Ala Thr805 810 815Asp Ile Glu Val Phe Trp Ala Ser Pro Leu Glu Lys Asn Arg Gly Arg820 825 830Ile Gln Gly Tyr Glu Val Lys Tyr Trp Arg His Glu Asp Lys Glu Glu835 840 845Asn Ala Arg Lys Ile Arg Thr Val Gly Asn Gln Thr Ser Thr Lys Ile850 855 860Thr Asn Leu Lys Gly Ser Val Leu Tyr His Leu Ala Val Lys Ala Tyr865 870 875 880Asn Ser Ala Gly Thr Gly Pro Ser Ser Ala Thr Val Asn Val Thr Thr885 890 895Arg Lys Pro Pro Pro Ser Gln Pro Pro Gly Asn Ile Ile Trp Asn Ser900 905 910Ser Asp Ser Lys Ile Ile Leu Asn Trp Asp Gln Val Lys Ala Leu Asp915 920 925Asn Glu Ser Glu Val Lys Gly Tyr Lys Val Leu Tyr Arg Trp Asn Arg930 935 940Gln Ser Ser Thr Ser Val Ile Glu Thr Asn Lys Thr Ser Val Glu Leu945 950 955 960Ser Leu Pro Phe Asp Glu Asp Tyr Ile Ile Glu Ile Lys Pro Phe Ser965 970 975Asp Gly Gly Asp Gly Ser Ser Ser Glu Gln Ile Arg Ile Pro Lys Ile980 985 990Ser Asn Ala Tyr Ala Arg Gly Ser Gly Ala Ser Thr Ser Asn Ala Cys995 10001005Thr Leu Ser Ala Ile Ser Thr Ile Met Ile Ser Leu Thr Ala Arg Ser101010151020Ser Leu1025<210>56<211>844<212>PRT<213>人(Homo sapiens)<400>56Met Asp Asn Pro Gln Ala Leu Pro Leu Phe Leu Leu Leu Ala Ser Leu1 5 10 15Val Gly Ile Leu Thr Leu Arg Ala Ser Ser Gly Leu Gln Gln Thr Asn20 25 30Phe Ser Ser Ala Phe Ser Ser Asp Ser Lys Ser Ser Ser Gln Gly Leu35 40 45Gly Val Glu Val Pro Ser Ile Lys Pro Pro Ser Trp Lys Val Pro Asp50 55 60Gln Phe Leu Asp Ser Lys Ala Ser Ala Gly Ile Ser Asp Ser Ser Trp65 70 75 80Phe Pro Glu Ala Leu Ser Ser Asn Met Ser Gly Ser Phe Trp Ser Asn85 90 95Val Ser Ala Glu Gly Gln Asp Leu Ser Pro Val Ser Pro Phe Ser Glu
100 105 110Thr Pro Gly Ser Glu Val Phe Pro Asp Ile Ser Asp Pro Gln Val Pro115 120 125Ala Lys Asp Pro Lys Pro Ser Phe Thr Val Lys Thr Pro Ala Ser Asn130 135 140Ile Ser Thr Gln Val Ser His Thr Lys Leu Ser Val Glu Ala Pro Asp145 150 155 160Ser Lys Phe Ser Pro Asp Asp Met Asp Leu Lys Leu Ser Ala Gln Ser165 170 175Pro Glu Ser Lys Phe Ser Ala Glu Thr His Ser Ala Ala Ser Phe Pro180 185 190Gln Gln Val Gly Gly Pro Leu Ala Val Leu Val Gly Thr Thr Ile Arg195 200 205Leu Pro Leu Val Pro Ile Pro Asn Pro Gly Pro Pro Thr Ser Leu Val210 215 220Val Trp Arg Arg Gly Ser Lys Val Leu Ala Ala Gly Gly Leu Gly Pro225 230 235 240Gly Ala Pro Leu Ile Ser Leu Asp Pro Ala His Arg Asp His Leu Arg245 250 255Phe Asp Gln Ala Arg Gly Val Leu Glu Leu Ala Ser Ala Gln Leu Asp260 265 270Asp Ala Gly Val Tyr Thr Ala Glu Val Ile Arg Ala Gly Val Ser Gln275 280 285Gln Thr His Glu Phe Thr Val Gly Val Tyr Glu Pro Leu Pro Gln Leu290 295 300Ser Val Gln Pro Lys Ala Pro Glu Thr Glu Glu Gly Ala Ala Glu Leu305 310 315 320Arg Leu Arg Cys Leu Gly Trp Gly Pro Gly Arg Gly Glu Leu Ser Trp325 330 335Ser Arg Asp Gly Arg Ala Leu Glu Ala Ala Glu Ser Glu Gly Ala Glu340 345 350Thr Pro Arg Met Arg Ser Glu Gly Asp Gln Leu Leu Ile Val Arg Pro355 360 365Val Arg Ser Asp His Ala Arg Tyr Thr Cys Arg Val Arg Ser Pro Phe370 375 380Gly His Arg Glu Ala Ala Ala Asp Val Ser Val Phe Tyr Gly Pro Asp385 390 395 400Pro Pro Thr Ile Thr Val Ser Ser Asp Arg Asp Ala Ala Pro Ala Arg405 410 415Phe Val Thr Ala Gly Ser Asn Val Thr Leu Arg Cys Ala Ala Ala Ser420 425 430Arg Pro Pro Ala Asp Ile Thr Trp Ser Leu Ala Asp Pro Ala Glu Ala435 440 445Ala Val Pro Ala Gly Ser Arg Leu Leu Leu Pro Ala Val Gly Pro Gly450 455 460His Ala Gly Thr Tyr Ala Cys Leu Ala Ala Asn Pro Arg Thr Gly Arg465 470 475 480Arg Arg Arg Ser Leu Leu Asn Leu Thr Val Ala Asp Leu Pro Pro Gly485 490 495Ala Pro Gln Cys Ser Val Glu Gly Gly Pro Gly Asp Arg Ser Leu Arg500 505 510Phe Arg Cys Ser Trp Pro Gly Gly Ala Pro Ala Ala Ser Leu Gln Phe515 520 525Gln Gly Leu Pro Glu Gly Ile Arg Ala Gly Pro Val Ser Ser Val Leu530 535 540Leu Ala Ala Val Pro Ala His Pro Arg Leu Ser Gly Val Pro Ile Thr545 550 555 560Cys Leu Ala Arg His Leu Val Ala Thr Arg Thr Cys Thr Val Thr Pro565 570 575Glu Ala Pro Arg Glu Val Leu Leu His Pro Leu Val Ala Glu Thr Arg580 585 590Leu Gly Glu Ala Glu Val Ala Leu Glu Ala Ser Gly Cys Pro Pro Pro595 600 605Ser Arg Ala Ser Trp Ala Arg Glu Gly Arg Pro Leu Ala Pro Gly Gly610 615 620Gly Ser Arg Leu Arg Leu Ser Gln Asp Gly Arg Lys Leu His Ile Gly625 630 635 640Asn Phe Ser Leu Asp Trp Asp Leu Gly Asn Tyr Ser Val Leu Cys Ser645 650 655Gly Ala Leu Gly Ala Gly Gly Asp Gln Ile Thr Leu Ile Asp Gly Pro660 665 670Ala Leu Gly Arg Thr Ser Thr Tyr Arg Asp Trp Val Ser Leu Leu Ile675 680 685Leu Gly Pro Gln Glu Arg Ser Ala Val Val Pro Leu Pro Pro Arg Asn690 695 700Pro Gly Thr Trp Thr Phe Arg Ile Leu Pro Ile Leu Gly Gly Gln Pro705 710 715 720Gly Thr Pro Ser Gln Ser Arg Val Tyr Arg Ala Gly Pro Thr Leu Ser725 730 735His Gly Ala Ile Ala Gly Ile Val Leu Gly Ser Leu Leu Gly Leu Ala740 745 750Leu Leu Ala Val Leu Leu Leu Leu Cys Ile Cys Cys Leu Cys Arg Phe755 760 765Arg Gly Lys Thr Pro Glu Lys Lys Lys His Pro Ser Thr Leu Val Pro770 775 780Val Val Thr Pro Ser Glu Lys Lys Met His Ser Val Thr Pro Val Glu785 790 795 800Ile Ser Trp Pro Leu Asp Leu Lys Val Pro Leu Glu Asp His Ser Ser805 810 815Thr Arg Ala Tyr Gln Ala Thr Asp Pro Ser Ser Val Val Ser Val Gly820 825 830Gly Gly Ser Lys Thr Val Arg Ala Ala Thr Gln Val835 840<210>57<211>782<212>PRT<213>人(Homo sapiens)<400>57Met Asp Asn Pro Gln Ala Leu Pro Leu Phe Leu Leu Leu Ala Ser Leu1 5 10 15Val Gly Ile Leu Thr Leu Arg Ala Ser Ser Gly Leu Gln Gln Thr Asn20 25 30Phe Ser Ser Ala Phe Ser Ser Asp Ser Lys Ser Ser Ser Gln Gly Leu35 40 45Gly Val Glu Val Pro Ser Ile Lys Pro Pro Ser Trp Lys Val Pro Asp50 55 60Gln Phe Leu Asp Ser Lys Ala Ser Ala Gly Ile Ser Asp Ser Ser Trp65 70 75 80Phe Pro Glu Ala Leu Ser Ser Asn Met Ser Gly Ser Phe Trp Ser Asn85 90 95Val Ser Ala Glu Gly Gln Asp Leu Ser Pro Val Ser Pro Phe Ser Glu100 105 110Thr Pro Gly Ser Glu Val Phe Pro Asp Ile Ser Asp Pro Gln Val Pro115 120 125Ala Lys Asp Pro Lys Pro Ser Phe Thr Val Lys Thr Pro Ala Ser Asn130 135 140Ile Ser Thr Gln Val Ser His Thr Lys Leu Ser Val Glu Ala Pro Asp145 150 155 160Ser Lys Phe Ser Pro Asp Asp Met Asp Leu Lys Leu Ser Ala Gln Ser165 170 175Pro Glu Ser Lys Phe Ser Ala Glu Thr His Ser Ala Ala Ser Phe Pro180 185 190Gln Gln Val Gly Gly Pro Leu Ala Val Leu Val Gly Thr Thr Ile Arg195 200 205Leu Pro Leu Val Pro Ile Pro Asn Pro Gly Pro Pro Thr Ser Leu Val210 215 220Val Trp Arg Arg Gly Ser Lys Val Leu Ala Ala Gly Gly Leu Gly Pro225 230 235 240Gly Ala Pro Leu Ile Ser Leu Asp Pro Ala His Arg Asp His Leu Arg245 250 255Phe Asp Gln Ala Arg Gly Val Leu Glu Leu Ala Ser Ala Gln Leu Asp260 265 270Asp Ala Gly Val Tyr Thr Ala Glu Val Ile Arg Ala Gly Val Ser Gln275 280 285Gln Thr His Glu Phe Thr Val Gly Val Tyr Glu Pro Leu Pro Gln Leu290 295 300Ser Val Gln Pro Lys Ala Pro Glu Thr Glu Glu Gly Ala Ala Glu Leu305 310 315 320Arg Leu Arg Cys Leu Gly Trp Gly Pro Gly Arg Gly Glu Leu Ser Trp325 330 335Ser Arg Asp Gly Arg Ala Leu Glu Ala Ala Glu Ser Glu Gly Ala Glu340 345 350Thr Pro Arg Met Arg Ser Glu Gly Asp Gln Leu Leu Ile Val Arg Pro355 360 365Val Arg Ser Asp His Ala Arg Tyr Thr Cys Arg Val Arg Ser Pro Phe370 375 380Gly His Arg Glu Ala Ala Ala Asp Val Ser Val Phe Tyr Gly Pro Asp385 390 395 400Pro Pro Thr Ile Thr Val Ser Ser Asp Arg Asp Ala Ala Pro Ala Arg405 410 415Phe Val Thr Ala Gly Ser Asn Val Thr Leu Arg Cys Ala Ala Ala Ser420 425 430Arg Pro Pro Ala Asp Ile Thr Trp Ser Leu Ala Asp Pro Ala Glu Ala435 440 445Ala Val Pro Ala Gly Ser Arg Leu Leu Leu Pro Ala Val Gly Pro Gly450 455 460His Ala Gly Thr Tyr Ala Cys Leu Ala Ala Asn Pro Arg Thr Gly Arg465 470 475 480Arg Arg Arg Ser Leu Leu Asn Leu Thr Val Ala Asp Leu Pro Pro Gly485 490 495Ala Pro Gln Cys Ser Val Glu Gly Gly Pro Gly Asp Arg Ser Leu Arg500 505 510Phe Arg Cys Ser Trp Pro Gly Gly Ala Pro Ala Ala Ser Leu Gln Phe515 520 525Gln Gly Leu Pro Glu Gly Ile Arg Ala Gly Pro Val Ser Ser Val Leu530 535 540Leu Ala Ala Val Pro Ala His Pro Arg Leu Ser Gly Val Pro Ile Thr545 550 555 560Cys Leu Ala Arg His Leu Val Ala Thr Arg Thr Cys Thr Val Thr Pro565 570 575Glu Ala Pro Arg Glu Val Leu Leu His Pro Leu Val Ala Glu Thr Arg580 585 590Leu Gly Glu Ala Glu Val Ala Leu Glu Ala Ser Gly Cys Pro Pro Pro595 600 605Ser Arg Ala Ser Trp Ala Arg Glu Gly Arg Pro Leu Ala Pro Gly Gly
610 615 620Gly Ser Arg Leu Arg Leu Ser Gln Asp Gly Arg Lys Leu His Ile Gly625 630 635 640Asn Phe Ser Leu Asp Trp Asp Leu Gly Asn Tyr Ser Val Leu Cys Ser645 650 655Gly Ala Leu Gly Ala Gly Gly Asp Gln Ile Thr Leu Ile Gly Pro Thr660 665 670Leu Ser His Gly Ala Ile Ala Gly Ile Val Leu Gly Ser Leu Leu Gly675 680 685Leu Ala Leu Leu Ala Val Leu Leu Leu Leu Cys Ile Cys Cys Leu Cys690 695 700Arg Phe Arg Gly Lys Thr Pro Glu Lys Lys Lys His Pro Ser Thr Leu705 710 715 720Val Pro Val Val Thr Pro Ser Glu Lys Lys Met His Ser Val Thr Pro725 730 735Val Glu Ile Ser Trp Pro Leu Asp Leu Lys Val Pro Leu Glu Asp His740 745 750Ser Ser Thr Arg Ala Tyr Gln Ala Thr Asp Pro Ser Ser Val Val Ser755 760 765Val Gly Gly Gly Ser Lys Thr Val Arg Ala Ala Thr Gln Val770 775 780<210>58<211>262<212>PRT<213>人(Homo sapiens)<400>58Met Asp Ser Leu Val Thr Ala Asn Thr Lys Phe Cys Phe Asp Leu Phe1 5 10 15Gln Glu Ile Gly Lys Asp Asp Arg His Lys Asn Ile Phe Phe Ser Pro20 25 30Leu Ser Leu Ser Ala Ala Leu Gly Met Val Arg Leu Gly Ala Arg Ser35 40 45Asp Ser Ala His Gln Ile Asp Glu Ala Gly Ser Leu Asn Asn Glu Ser50 55 60Gly Leu Val Ser Cys Tyr Phe Gly Gln Leu Leu Ser Lys Leu Asp Arg65 70 75 80Ile Lys Thr Asp Tyr Thr Leu Ser Ile Ala Asn Arg Leu Tyr Gly Glu85 90 95Gln Glu Phe Pro Ile Cys Gln Glu Tyr Leu Asp Gly Val Ile Gln Phe100 105 110Tyr His Thr Thr Ile Glu Ser Val Asp Phe Gln Lys Asn Pro Glu Lys115 120 125Ser Arg Gln Glu Ile Asn Phe Trp Val Glu Cys Gln Ser Gln Gly Lys130 135 140Ile Lys Glu Leu Phe Ser Lys Asp Ala Ile Asn Ala Glu Thr Val Leu145 150 155 160Val Leu Val Asn Ala Val Tyr Phe Lys Ala Lys Trp Glu Thr Tyr Phe165 170 175Asp His Glu Asn Thr Val Asp Ala Pro Phe Cys Leu Asn Ala Asn Glu180 185 190Asn Lys Ser Val Lys Met Met Thr Gln Lys Gly Leu Tyr Arg Ile Gly195 200 205Phe Ile Glu Glu Val Lys Ala Gln Ile Leu Glu Met Arg Tyr Thr Lys210 215 220Gly Lys Leu Ser Met Phe Val Leu Leu Pro Ser His Ser Lys Asp Asn225 230 235 240Leu Lys Gly Leu Glu Glu Val Asn Leu His Phe His Ile Ser Thr Lys
245250255Tyr Leu Met Ile Asp Leu260<210>59<211>394<212>PRT<213>人(Homo sapiens)<400>59Met Asp Ser Leu Val Thr Ala Asn Thr Lys Phe Cys Phe Asp Leu Phe1 5 10 15Gln Glu Ile Gly Lys Asp Asp Arg His Lys Asn Ile Phe Phe Ser Pro20 25 30Leu Ser Leu Ser Ala Ala Leu Gly Met Val Arg Leu Gly Ala Arg Ser35 40 45Asp Ser Ala His Gln Ile Asp Glu Val Leu His Phe Asn Lys Thr Thr50 55 60Glu Pro Leu Asp Gln Gln Ala Gly Ser Leu Asn Asn Glu Ser Gly Leu65 70 75 80Val Ser Cys Tyr Phe Gly Gln Leu Leu Ser Lys Leu Asp Arg Ile Lys85 90 95Thr Asp Tyr Thr Leu Ser Ile Ala Asn Arg Leu Tyr Gly Glu Gln Glu100 105 110Phe Pro Ile Cys Gln Glu Tyr Leu Asp Gly Val Ile Gln Phe Tyr His115 120 125Thr Thr Ile Glu Ser Val Asp Phe Gln Lys Asn Pro Glu Lys Ser Arg130 135 140Gln Glu Ile Asn Phe Trp Val Glu Cys Gln Ser Gln Gly Lys Ile Lys145 150 155 160Glu Leu Phe Ser Lys Asp Ala Ile Asn Ala Glu Thr Val Leu Val Leu165 170 175Val Asn Ala Val Tyr Phe Lys Ala Lys Trp Glu Thr Tyr Phe Asp His180 185 190Glu Asn Thr Val Asp Ala Pro Phe Cys Leu Asn Ala Asn Glu Asn Lys195 200 205Ser Val Lys Met Met Thr Gln Lys Gly Leu Tyr Arg Ile Gly Phe Ile210 215 220Glu Glu Val Lys Ala Gln Ile Leu Glu Met Arg Tyr Thr Lys Gly Lys225 230 235 240Leu Ser Met Phe Val Leu Leu Pro Ser His Ser Lys Asp Asn Leu Lys245 250 255Gly Leu Glu Glu Leu Glu Arg Lys Ile Thr Tyr Glu Lys Met Val Ala260 265 270Trp Ser Ser Ser Glu Asn Met Ser Glu Glu Ser Val Val Leu Ser Phe275 280 285Pro Arg Phe Thr Leu Glu Asp Ser Tyr Asp Leu Asn Ser Ile Leu Gln290 295 300Asp Met Gly Ile Thr Asp Ile Phe Asp Glu Thr Arg Ala Asp Leu Thr305 310 315 320Gly Ile Ser Pro Ser Pro Asn Leu Tyr Leu Ser Lys Ile Ile His Lys325 330 335Thr Phe Val Glu Val Asp Glu Asn Gly Thr Gln Ala Ala Ala Ala Thr340 345 350Gly Ala Val Val Ser Glu Arg Ser Leu Arg Ser Trp Val Glu Phe Asn355 360 365Ala Asn His Pro Phe Leu Phe Phe Ile Arg His Asn Lys Thr Gln Thr370 375 380Ile Leu Phe Tyr Gly Arg Val Cys Ser Pro385 390<210>60<211>471<212>PRT<213>人(Homo sapiens)<400>60Met Ser Val Pro Leu Leu Lys Ile Gly Val Val Leu Ser Thr Met Ala1 5 10 15Met Ile Thr Asn Trp Met Ser Gln Thr Leu Pro Ser Leu Val Gly Leu20 25 30Asn Thr Thr Lys Leu Ser Ala Ala Gly Gly Gly Thr Leu Asp Arg Ser35 40 45Thr Gly Val Leu Pro Thr Asn Pro Glu Glu Ser Trp Gln Val Tyr Ser50 55 60Ser Ala Gln Asp Ser Glu Gly Arg Cys Ile Cys Thr Val Val Ala Pro65 70 75 80Gln Gln Thr Met Cys Ser Arg Asp Ala Arg Thr Lys Gln Leu Arg Gln85 90 95Leu Leu Glu Lys Val Gln Asn Met Ser Gln Ser Ile Glu Val Leu Asp100 105 110Arg Arg Thr Gln Arg Asp Leu Gln Tyr Val Glu Lys Met Glu Asn Gln115 120 125Met Lys Gly Leu Glu Ser Lys Phe Lys Gln Ala Ile Lys Ala Lys Met130 135 140Asp Glu Leu Arg Pro Leu Ile Pro Val Leu Glu Glu Tyr Lys Ala Asp145 150 155 160Ala Lys Leu Val Leu Gln Phe Lys Glu Glu Val Gln Asn Leu Thr Ser165 170 175Val Leu Asn Glu Leu Gln Glu Glu Ile Gly Ala Tyr Asp Tyr Asp Glu180 185 190Leu Gln Ser Arg Val Ser Asn Leu Glu Glu Arg Leu Arg Ala Cys Met195 200 205Gln Lys Leu Ala Cys Gly Lys Leu Thr Gly Ile Ser Asp Pro Val Thr210 215 220Val Lys Thr Ser Gly Ser Arg Phe Gly Ser Trp Met Thr Asp Pro Leu225 230 235 240Ala Pro Glu Gly Asp Asn Arg Val Trp Tyr Met Asp Gly Tyr His Asn245 250 255Asn Arg Phe Val Arg Glu Tyr Lys Ser Met Val Asp Phe Met Asn Thr260 265 270Asp Asn Phe Thr Ser His Arg Leu Pro His Pro Trp Ser Gly Thr Gly275 280 285Gln Val Val Tyr Asn Gly Ser Ile Tyr Phe Asn Lys Phe Gln Ser His290 295 300Ile Ile Ile Arg Phe Asp Leu Lys Thr Glu Thr Ile Leu Lys Thr Arg305 310 315 320Ser Leu Asp Tyr Ala Gly Tyr Asn Asn Met Tyr His Tyr Ala Trp Gly325 330 335Gly His Ser Asp Ile Asp Leu Met Val Asp Glu Ser Gly Leu Trp Ala340 345 350Val Tyr Ala Thr Asn Gln Asn Ala Gly Asn Ile Val Val Ser Arg Leu355 360 365Asp Pro Val Ser Leu Gln Thr Leu Gln Thr Trp Asn Thr Ser Tyr Pro370 375 380Lys Arg Ser Ala Gly Glu Ala Phe Ile Ile Cys Gly Thr Leu Tyr Val385 390 395 400Thr Asn Gly Tyr Ser Gly Gly Thr Lys Val His Tyr Ala Tyr Gln Thr
405 410 415Asn Ala Ser Thr Tyr Glu Tyr Ile Asp Ile Pro Phe Gln Asn Lys Tyr420 425 430Ser His Ile Ser Met Leu Asp Tyr Asn Pro Lys Asp Arg Ala Leu Tyr435 440 445Ala Trp Asn Asn Gly His Gln Ile Leu Tyr Asn Val Thr Leu Phe His450 455 460Val Ile Arg Ser Asp Glu Leu465 470<210>61<211>485<212>PRT<213>人(Homo sapiens)<400>61Met Ser Val Pro Leu Leu Lys Ile Gly Val Val Leu Ser Thr Met Ala1 5 10 15Met Ile Thr Asn Trp Met Ser Gln Thr Leu Pro Ser Leu Val Gly Leu20 25 30Asn Thr Thr Lys Leu Ser Ala Ala Gly Gly Gly Thr Leu Asp Arg Ser35 40 45Thr Gly Val Leu Pro Thr Asn Pro Glu Glu Ser Trp Gln Val Tyr Ser50 55 60Ser Ala Gln Asp Ser Glu Gly Arg Cys Ile Cys Thr Val Val Ala Pro65 70 75 80Gln Gln Thr Met Cys Ser Arg Asp Ala Arg Thr Lys Gln Leu Arg Gln85 90 95Leu Leu Glu Lys Val Gln Asn Met Ser Gln Ser Ile Glu Val Leu Asp100 105 110Arg Arg Thr Gln Arg Asp Leu Gln Tyr Val Glu Lys Met Glu Asn Gln115 120 125Met Lys Gly Leu Glu Ser Lys Phe Lys Gln Val Glu Glu Ile Ile Ser130 135 140Tyr Thr Trp Pro Arg Gln Phe Lys Ala Ile Lys Ala Lys Met Asp Glu145 150 155 160Leu Arg Pro Leu Ile Pro Val Leu Glu Glu Tyr Lys Ala Asp Ala Lys165 170 175Leu Val Leu Gln Phe Lys Glu Glu Val Gln Asn Leu Thr Ser Val Leu180 185 190Asn Glu Leu Gln Glu Glu Ile Gly Ala Tyr Asp Tyr Asp Glu Leu Gln195 200 205Ser Arg Val Ser Asn Leu Glu Glu Arg Leu Arg Ala Cys Met Gln Lys210 215 220Leu Ala Cys Gly Lys Leu Thr Gly Ile Ser Asp Pro Val Thr Val Lys225 230 235 240Thr Ser Gly Ser Arg Phe Gly Ser Trp Met Thr Asp Pro Leu Ala Pro245 250 255Glu Gly Asp Asn Arg Val Trp Tyr Met Asp Gly Tyr His Asn Asn Arg260 265 270Phe Val Arg Glu Tyr Lys Ser Met Val Asp Phe Met Asn Thr Asp Asn275 280 285Phe Thr Ser His Arg Leu Pro His Pro Trp Ser Gly Thr Gly Gln Val290 295 300Val Tyr Asn Gly Ser Ile Tyr Phe Asn Lys Phe Gln Ser His Ile Ile305 310 315 320Ile Arg Phe Asp Leu Lys Thr Glu Thr Ile Leu Lys Thr Arg Ser Leu325 330 335Asp Tyr Ala Gly Tyr Asn Asn Met Tyr His Tyr Ala Trp Gly Gly His
340 345 350Ser Asp Ile Asp Leu Met Val Asp Glu Ser Gly Leu Trp Ala Val Tyr355 360 365Ala Thr Asn Gln Asn Ala Gly Asn Ile Val Val Ser Arg Leu Asp Pro370 375 380Val Ser Leu Gln Thr Leu Gln Thr Trp Asn Thr Ser Tyr Pro Lys Arg385 390 395 400Ser Ala Gly Glu Ala Phe Ile Ile Cys Gly Thr Leu Tyr Val Thr Asn405 410 415Gly Tyr Ser Gly Gly Thr Lys Val His Tyr Ala Tyr Gln Thr Asn Ala420 425 430Ser Thr Tyr Glu Tyr Ile Asp Ile Pro Phe Gln Asn Lys Tyr Ser His435 440 445Ile Ser Met Leu Asp Tyr Asn Pro Lys Asp Arg Ala Leu Tyr Ala Trp450 455 460Asn Asn Gly His Gln Ile Leu Tyr Asn Val Thr Leu Phe His Val Ile465 470 475 480Arg Ser Asp Glu Leu485<210>62<211>286<212>PRT<213>人(Homo sapiens)<400>62Met Leu His Leu Leu Ala Leu Phe Leu His Cys Leu Pro Leu Ala Ser1 5 10 15Gly Asp Tyr Asp Ile Cys Lys Ser Trp Val Thr Thr Asp Glu Gly Pro20 25 30Thr Trp Glu Phe Tyr Ala Cys Gln Pro Lys Val Met Arg Leu Lys Asp35 40 45Tyr Val Lys Val Lys Val Glu Pro Ser Gly Ile Thr Cys Gly Asp Pro50 55 60Pro Glu Arg Phe Cys Ser His Glu Asn Pro Tyr Leu Cys Ser Asn Glu65 70 75 80Cys Asp Ala Ser Asn Pro Asp Leu Ala His Pro Pro Arg Leu Met Phe85 90 95Asp Lys Glu Glu Glu Gly Leu Ala Thr Tyr Trp Gln Ser Ile Thr Trp100 105 110Ser Arg Tyr Pro Ser Pro Leu Glu Ala Asn Ile Thr Leu Ser Trp Asn115 120 125Lys Thr Val Glu Leu Thr Asp Asp Val Val Met Thr Phe Glu Tyr Gly130 135 140Arg Pro Thr Val Met Val Leu Glu Lys Ser Leu Asp Asn Gly Arg Thr145 150 155 160Trp Gln Pro Tyr Gln Phe Tyr Ala Glu Asp Cys Met Glu Ala Phe Gly165 170 175Met Ser Ala Arg Arg Ala Arg Asp Met Ser Ser Ser Ser Ala His Arg180 185 190Val Leu Cys Thr Glu Glu Tyr Ser Arg Trp Ala Gly Ser Lys Lys Glu195 200 205Lys His Val Arg Phe Glu Val Arg Asp Arg Phe Ala Ile Phe Ala Gly210 215 220Pro Asp Leu Arg Asn Met Asp Asn Leu Tyr Thr Arg Leu Glu Ser Ala225 230 235 240Lys Gly Leu Lys Glu Phe Phe Thr Leu Thr Asp Leu Arg Met Arg Leu245 250 255Leu Arg Pro Ala Leu Gly Gly Thr Tyr Val Gln Arg Glu Asn Leu Tyr
260 265 270Lys Tyr Phe Tyr Ala Ile Ser Asn Ile Glu Val Ile Gly Arg275 280 285<210>63<211>533<212>PRT<213>人(Homo sapiens)<400>63Met Leu His Leu Leu Ala Leu Phe Leu His Cys Leu Pro Leu Ala Ser1 5 10 15Gly Asp Tyr Asp Ile Cys Lys Ser Trp Val Thr Thr Asp Glu Gly Pro20 25 30Thr Trp Glu Phe Tyr Ala Cys Gln Pro Lys Val Met Arg Leu Lys Asp35 40 45Tyr Val Lys Val Lys Val Glu Pro Ser Gly Ile Thr Cys Gly Asp Pro50 55 60Pro Glu Arg Phe Cys Ser His Glu Asn Pro Tyr Leu Cys Ser Asn Glu65 70 75 80Cys Asp Ala Ser Asn Pro Asp Leu Ala His Pro Pro Arg Leu Met Phe85 90 95Asp Lys Glu Glu Glu Gly Leu Ala Thr Tyr Trp Gln Ser Ile Thr Trp100 105 110Ser Arg Tyr Pro Ser Pro Leu Glu Ala Asn Ile Thr Leu Ser Trp Asn115 120 125Lys Thr Val Glu Leu Thr Asp Asp Val Val Met Thr Phe Glu Tyr Gly130 135 140Arg Pro Thr Val Met Val Leu Glu Lys Ser Leu Asp Asn Gly Arg Thr145 150 155 160Trp Gln Pro Tyr Gln Phe Tyr Ala Glu Asp Cys Met Glu Ala Phe Gly165 170 175Met Ser Ala Arg Arg Ala Arg Asp Met Ser Ser Ser Ser Ala His Arg180 185 190Val Leu Cys Thr Glu Glu Tyr Ser Arg Trp Ala Gly Ser Lys Lys Glu195 200 205Lys His Val Arg Phe Glu Val Arg Asp Arg Phe Ala Ile Phe Ala Gly210 215 220Pro Asp Leu Arg Asn Met Asp Asn Leu Tyr Thr Arg Leu Glu Ser Ala225 230 235 240Lys Gly Leu Lys Glu Phe Phe Thr Leu Thr Asp Leu Arg Met Arg Leu245 250 255Leu Arg Pro Ala Leu Gly Gly Thr Tyr Val Gln Arg Glu Asn Leu Tyr260 265 270Lys Tyr Phe Tyr Ala Ile Ser Asn Ile Glu Val Ile Gly Arg Cys Lys275 280 285Cys Asn Leu His Ala Asn Leu Cys Ser Met Arg Glu Gly Ser Leu Gln290 295 300Cys Glu Cys Glu His Asn Thr Thr Gly Pro Asp Cys Gly Lys Cys Lys305 310 315 320Lys Asn Phe Arg Thr Arg Ser Trp Arg Ala Gly Ser Tyr Leu Pro Leu325 330 335Pro His Gly Ser Pro Asn Ala Cys Thr Pro Pro Ser Pro Arg Glu Leu340 345 350Gly Ala Asp Cys Glu Cys Tyr Gly His Ser Asn Arg Cys Ser Tyr Ile355 360 365Asp Phe Leu Asn Val Val Thr Cys Val Ser Cys Lys His Asn Thr Arg370 375 380Gly Gln His Cys Gln His Cys Arg Leu Gly Tyr Tyr Arg Asn Gly Ser385 390 395 400Ala Glu Leu Asp Asp Glu Asn Val Cys Ile Glu Cys Asn Cys Asn Gln405 410 415Ile Gly Ser Val His Asp Arg Cys Asn Glu Thr Gly Phe Cys Glu Cys420 425 430Arg Glu Gly Ala Ala Gly Pro Lys Cys Asp Asp Cys Leu Pro Thr His435 440 445Tyr Trp Arg Gln Gly Cys Tyr Pro Asn Val Cys Asp Asp Asp Gln Leu450 455 460Leu Cys Gln Asn Gly Gly Thr Cys Leu Gln Asn Gln Arg Cys Ala Cys465 470 475 480Pro Arg Gly Tyr Thr Gly Val Arg Cys Glu Gln Pro Arg Cys Asp Pro485 490 495Ala Asp Asp Asp Gly Gly Leu Asp Cys Asp Arg Ala Pro Gly Ala Ala500 505 510Pro Arg Pro Ala Thr Leu Leu Gly Cys Leu Leu Leu Leu Gly Leu Ala515 520 525Ala Arg Leu Gly Arg530<210>64<211>495<212>PRT<213>人(Homo sapiens)<400>64Met Phe Ala Asn Ser Pro Gly Cys Ser Asn Met Leu His Tyr Val Tyr1 5 10 15Cys Ala Cys Gly His Gly Leu Gln Leu Val Arg Ser Val Ser Ser Ser20 25 30Val Asp Glu Gly Gly Thr Cys His Cys Met Val His Leu Pro Asn Asn35 40 45Pro Ile Pro Leu Glu Gln Leu Glu Gln Leu Gln Ser Thr Ala Gln Glu50 55 60Leu Ile Cys Lys Tyr Glu Gln Lys Leu Ser Arg Cys Ala Arg Ala Ile65 70 75 80Glu Asp Lys Asp Asn Glu Val Leu Glu Met Ser His Met Leu Lys Ser85 90 95Trp Asn Pro Ser Ala Leu Ala Ser Pro Tyr Glu Asn Pro Gly Phe Asn100 105 110Leu Leu Cys Leu Glu Leu Glu Gly Ala Gln Glu Leu Val Thr Gln Leu115 120 125Lys Ala Met Gly Gly Val Ser Val Ala Gly Asp Leu Leu His Gln Leu130 135 140Gln Ser Gln Val Thr Asn Ala Ser Leu Thr Leu Lys Leu Leu Ala Asp145 150 155 160Ser Asp Gln Cys Ser Phe Gly Ala Leu Gln Gln Glu Val Asp Val Leu165 170 175Glu Ser Gln Leu Ser Glu Cys Glu Arg Glu Lys Glu Lys Glu Gly Leu180 185 190Trp Thr Pro Trp Thr Thr Pro Pro Pro Ala Ser Cys Ala His Gly Gly195 200 205Leu Gln Glu Val Ser Lys Ser Leu Val Val Gln Leu Thr Arg Arg Gly210 215 220Phe Ser Tyr Lys Ala Gly Pro Trp Gly Arg Asp Ser Ala Pro Asn Pro225 230 235 240Ala Ser Ser Leu Tyr Trp Val Ala Pro Leu Arg Thr Asp Gly Arg Tyr245 250 255Phe Asp Tyr Tyr Arg Leu Pro Pro Ser Tyr Asn Asp Leu Ala Leu Met
260 265 270Lys Asn Tyr Glu Glu Arg Lys Met Gly Tyr Gly Asp Gly Ser Gly Asn275 280 285Val Val Tyr Lys Asn Phe Met Tyr Phe Asn Tyr Cys Gly Thr Ser Asp290 295 300Met Ala Lys Met Asp Leu Ser Ser Asn Thr Leu Val Leu Trp Arg Leu305 310 315 320Leu Pro Gly Ala Thr Tyr Asn Asn Arg Phe Ser Cys Ala Gly Val Pro325 330 335Trp Lys Asp Leu Asp Phe Ala Gly Asp Glu Lys Gly Leu Trp Val Leu340 345 350Tyr Ala Thr Glu Glu Ser Lys Gly Asn Leu Val Val Ser Arg Leu Asn355 360 365Ala Ser Thr Leu Glu Val Glu Lys Thr Trp Arg Thr Ser Gln Tyr Lys370 375 380Pro Ala Leu Ser Gly Ala Phe Met Ala Cys Gly Val Leu Tyr Ala Leu385 390 395 400His Ser Leu Asn Thr His Gln Glu Glu Ile Phe Tyr Ala Phe Asp Thr405 410 415Thr Thr Gly Gln Glu Arg Arg Leu Ser Ile Leu Leu Asp Lys Met Leu420 425 430Glu Lys Leu Gln Gly Ile Asn Tyr Cys Pro Ser Asp His Lys Pro Tyr435 440 445Val Phe Ser Asp Gly Tyr Leu Ile Asn Tyr Asp Leu Thr Phe Leu Thr450 455 460Met Lys Thr Arg Leu Pro Arg Pro Pro Thr Arg Arg Pro Ser Gly Ala465 470 475 480His Ala Pro Pro Lys Pro Val Lys Pro Asn Glu Ala Ser Arg Pro485 490 495<210>65<211>350<212>PRT<213>人(Homo sapiens)<400>65Met Arg Asn His Lys Lys Val Thr Asn Ala Ser Leu Thr Leu Lys Leu1 5 10 15Leu Ala Asp Ser Asp Gln Cys Ser Phe Gly Ala Leu Gln Gln Glu Val20 25 30Asp Val Leu Glu Ser Gln Leu Ser Glu Ser Ser Cys Ala His Gly Gly35 40 45Leu Gln Glu Val Ser Lys Ser Leu Val Val Gln Leu Thr Arg Arg Gly50 55 60Phe Ser Tyr Lys Ala Gly Pro Trp Gly Arg Asp Ser Ala Pro Asn Pro65 70 75 80Ala Ser Ser Leu Tyr Trp Val Ala Pro Leu Arg Thr Asp Gly Ser Tyr85 90 95Gly Cys His Pro Ile Ile Leu Asn Ala Gly Thr Trp Pro Arg Tyr Phe100 105 110Asp Tyr Tyr Arg Lcu Cys Lys Ser Tyr Asn Asp Leu Ala Leu Leu Lys115 120 125Asn Tyr Glu Glu Arg Lys Met Gly Tyr Gly Asp Gly Ser Gly Asn Val130 135 140Val Tyr Lys Asn Phe Met Tyr Phe Asn Tyr Cys Gly Thr Ser Asp Met145 150 155 160Ala Lys Met Asp Leu Ser Ser Asn Thr Leu Val Leu Trp Arg Leu Leu165 170 175Pro Gly Ala Thr Tyr Asn Asn Arg Phe Ser Cys Ala Gly Val Pro Trp
180 185 190Lys Asp Leu Asp Phe Ala Gly Asp Glu Lys Gly Leu Trp Val Leu Tyr195 200 205Ala Thr Glu Glu Ser Lys Gly Asn Leu Val Val Ser Arg Leu Asn Ala210 215 220Ser Thr Leu Glu Val Glu Lys Thr Trp Arg Thr Ser Gln Tyr Lys Pro225 230 235 240Ala Leu Ser Gly Ala Phe Met Ala Cys Gly Val Leu Tyr Ala Leu His245 250 255Ser Leu Asn Thr His Gln Glu Glu Ile Phe Tyr Ala Phe Asp Thr Thr260 265 270Thr Gly Gln Glu Arg Arg Leu Ser Ile Leu Leu Asp Lys Met Leu Glu275 280 285Lys Leu Gln Gly Ile Asn Tyr Cys Pro Ser Asp His Lys Pro Tyr Val290 295 300Phe Ser Asp Gly Tyr Leu Ile Asn Tyr Asp Leu Thr Phe Leu Thr Met305 310 315 320Lys Thr Arg Leu Pro Arg Pro Pro Thr Arg Arg Pro Ser Gly Ala His325 330 335Ala Pro Pro Lys Pro Val Lys Pro Asn Glu Ala Ser Arg Pro340 345 350<210>66<211>619<212>PRT<213>人(Homo sapiens)<400>66Met Gly Arg Gly Arg Ala Leu Leu Pro Ile Glu Met Leu Gln Leu Ser1 5 10 15Leu Arg Glu Glu Ser Asp Thr Ala Arg Met Gly Ala Gln Glu Gln Ile20 25 30Gly Leu Gln Asp Glu Ile Gln Ala Ala Asn Ala Gly Ile Ser Gly Ser35 40 45Pro Gly Val Asp Gly Val Val Asp Gly Gly Ser Ser Arg Gly Asp Pro50 55 60Ala Leu Thr Val Ser Val Cys Glu Val Pro Pro Val Arg Ser Pro Phe65 70 75 80Arg Thr His Pro Gln Leu Pro Val Arg Leu Pro Arg Asn Leu Glu Phe85 90 95Ser Val Pro Glu Arg Arg Thr Leu Arg Asn Arg Leu Thr Ser Ala Thr100 105 110Leu Ala Pro Pro Thr Arg His Met Leu Leu Leu Leu Leu Leu Leu Pro115 120 125Pro Leu Leu Cys Gly Arg Val Gly Ala Lys Glu Gln Lys Asp Tyr Leu130 135 140Leu Thr Met Gln Lys Ser Val Thr Val Gln Glu Gly Leu Cys Val Ser145 150 155 160Val Leu Cys Ser Phe Ser Tyr Pro Gln Asn Gly Trp Thr Ala Ser Asp165 170 175Pro Val His Gly Tyr Trp Phe Arg Ala Gly Asp His Val Ser Arg Asn180 185 190Ile Pro Val Ala Thr Asn Asn Pro Ala Arg Ala Val Gln Glu Glu Thr195 200 205Arg Asp Arg Phe His Leu Leu Gly Asp Pro Gln Asn Lys Asp Cys Thr210 215 220Leu Ser Ile Arg Asp Thr Arg Glu Ser Asp Ala Gly Thr Tyr Val Phe225 230 235 240Cys Val Glu Arg Gly Asn Met Lys Trp Asn Tyr Lys Tyr Asp Gln Leu
245 250 255Ser Val Asn Val Thr Ala Leu Thr His Met Pro Thr Phe Ser Ile Pro260 265 270Gly Thr Leu Glu Ser Gly His Pro Arg Asn Leu Thr Cys Ser Val Pro275 280 285Trp Ala Cys Glu Gln Gly Thr Pro Pro Thr Ile Thr Trp Met Gly Ala290 295 300Ser Val Ser Ser Leu Asp Pro Thr Ile Thr Arg Ser Ser Met Leu Ser305 310 315 320Leu Ile Pro Gln Pro Gln Asp His Gly Thr Ser Leu Thr Cys Gln Val325 330 335Thr Leu Pro Gly Ala Gly Val Thr Met Thr Arg Ala Val Arg Leu Asn340 345 350Ile Ser Tyr Pro Pro Gln Asn Leu Thr Met Thr Val Phe Gln Gly Asp355 360 365Gly Thr Ala Ser Thr Thr Leu Arg Asn Gly Ser Ala Leu Ser Val Leu370 375 380Glu Gly Gln Ser Leu His Leu Val Cys Ala Val Asp Ser Asn Pro Pro385 390 395 400Ala Arg Leu Ser Trp Thr Trp Gly Ser Leu Thr Leu Ser Pro Ser Gln405 410 415Ser Ser Asn Leu Gly Val Leu Glu Leu Pro Arg Val His Val Lys Asp420 425 430Glu Gly Glu Phe Thr Cys Arg Ala Gln Asn Pro Leu Gly Ser Gln His435 440 445Ile Ser Leu Ser Leu Ser Leu Gln Asn Glu Tyr Thr Gly Lys Met Arg450 455 460Pro Ile Ser Gly Val Thr Leu Gly Ala Phe Gly Gly Ala Gly Ala Thr465 470 475 480Ala Leu Val Phe Leu Tyr Phe Cys Ile Ile Phe Val Val Val Arg Ser485 490 495Cys Arg Lys Lys Ser Ala Arg Pro Ala Val Gly Val Gly Asp Thr Gly500 505 510Met Glu Asp Ala Asn Ala Val Arg Gly Ser Ala Ser Gln Met Glu Glu515 520 525Gly Thr Pro Gly Pro Pro Ser Trp Met Leu Ser Gly Ala Cys Trp Pro530 535 540His Cys Ser Ala Leu Thr Pro Phe Ser Ser Ser Ile Gln Gly Pro Leu545 550 555 560Ile Glu Ser Pro Ala Asp Asp Ser Pro Pro His His Ala Pro Pro Ala565 570 575Leu Ala Thr Pro Ser Pro Glu Glu Gly Glu Ile Gln Tyr Ala Ser Leu580 585 590Ser Phe His Lys Ala Arg Pro Gln Tyr Pro Gln Glu Gln Glu Ala Ile595 600 605Gly Tyr Glu Tyr Ser Glu Ile Asn Ile Pro Lys610 615<210>67<211>490<212>PRT<213>人(Homo sapiens)<400>67Met Leu Leu Leu Leu Leu Leu Leu Pro Pro Leu Leu Cys Gly Arg Val1 5 10 15Gly Ala Lys Glu Gln Lys Asp Tyr Leu Leu Thr Met Gln Lys Ser Val20 25 30Thr Val Gln Glu Gly Leu Cys Val Ser Val Leu Cys Ser Phe Ser Tyr
35 40 45Pro Gln Asn Gly Trp Thr Ala Ser Asp Pro Val His Gly Tyr Trp Phe50 55 60Arg Ala Gly Asp His Val Ser Arg Asn Ile Pro Val Ala Thr Asn Asn65 70 75 80Pro Ala Arg Ala Val Gln Glu Glu Thr Arg Asp Arg Phe His Leu Leu85 90 95Gly Asp Pro Gln Asn Lys Asp Cys Thr Leu Ser Ile Arg Asp Thr Arg100 105 110Glu Ser Asp Ala Gly Thr Tyr Val Phe Cys Val Glu Arg Gly Asn Met115 120 125Lys Trp Asn Tyr Lys Tyr Asp Gln Leu Ser Val Asn Val Thr Ala Leu130 135 140Thr His Met Pro Thr Phe Ser Ile Pro Gly Thr Leu Glu Ser Gly His145 150 155 160Pro Arg Asn Leu Thr Cys Ser Val Pro Trp Ala Cys Glu Gln Gly Thr165 170 175Pro Pro Thr Ile Thr Trp Met Gly Ala Ser Val Ser Ser Leu Asp Pro180 185 190Thr Ile Thr Arg Ser Ser Met Leu Ser Leu Ile Pro Gln Pro Gln Asp195 200 205His Gly Thr Ser Leu Thr Cys Gln Val Thr Leu Pro Gly Ala Gly Val210 215 220Thr Met Thr Arg Ala Val Arg Leu Asn Ile Ser Tyr Pro Pro Gln Asn225 230 235 240Leu Thr Met Thr Val Phe Gln Gly Asp Gly Thr Ala Ser Thr Thr Leu245 250 255Arg Asn Gly Ser Ala Leu Ser Val Leu Glu Gly Gln Ser Leu His Leu260 265 270Val Cys Ala Val Asp Ser Asn Pro Pro Ala Arg Leu Ser Trp Thr Trp275 280 285Gly Ser Leu Thr Leu Ser Pro Ser Gln Ser Ser Asn Leu Gly Val Leu290 295 300Glu Leu Pro Arg Val His Val Lys Asp Glu Gly Glu Phe Thr Cys Arg305 310 315 320Ala Gln Asn Pro Leu Gly Ser Gln His Ile Ser Leu Ser Leu Ser Leu325 330 335Gln Asn Glu Tyr Thr Gly Lys Met Arg Pro Ile Ser Gly Val Thr Leu340 345 350Gly Ala Phe Gly Gly Ala Gly Ala Thr Ala Leu Val Phe Leu Tyr Phe355 360 365Cys Ile Ile Phe Val Val Val Arg Ser Cys Arg Lys Lys Ser Ala Arg370 375 380Pro Ala Val Gly Val Gly Asp Thr Gly Met Glu Asp Ala Asn Ala Val385 390 395 400Arg Gly Ser Ala Ser Gln Gly Pro Leu Thr Glu Ser Trp Lys Asp Gly405 410 415Asn Pro Leu Lys Lys Pro Pro Pro Ala Val Ala Pro Ser Ser Gly Glu420 425 430Glu Gly Glu Leu His Tyr Ala Thr Leu Ser Phe His Lys Val Lys Pro435 440 445Gln Asp Pro Gln Gly Gln Glu Ala Thr Asp Ser Glu Tyr Ser Glu Ile450 455 460Lys Ile His Lys Arg Glu Thr Ala Glu Thr Gln Ala Cys Leu Arg Asn465 470 475 480His Asn Pro Ser Ser Lys Glu Val Arg Gly485 490<210>68
<211>462<212>PRT<213>人(Homo sapiens)<400>68Met Leu Pro Leu Trp Thr Leu Ser Leu Leu Leu Gly Ala Val Ala Gly1 5 10 15Lys Glu Val Cys Tyr Glu Arg Leu Gly Cys Phe Ser Asp Asp Ser Pro20 25 30Trp Ser Gly Ile Thr Glu Arg Pro Leu His Ile Leu Pro Trp Ser Pro35 40 45Lys Asp Val Asn Thr Arg Phe Leu Leu Tyr Thr Asn Glu Asn Pro Asn50 55 60Asn Phe Gln Glu Ile Ser Ala Val Asn Ser Ser Thr Ile Gln Ala Ser65 70 75 80Tyr Phe Gly Thr Asp Lys Ile Thr Arg Ile Asn Ile Ala Gly Trp Lys85 90 95Thr Asp Gly Lys Trp Gln Arg Asp Met Cys Asn Val Leu Leu Gln Leu100 105 110Glu Asp Ile Asn Cys Ile Asn Leu Asp Trp Ile Asn Gly Ser Arg Glu115 120 125Tyr Ile His Ala Val Asn Asn Leu Arg Val Val Gly Ala Glu Val Ala130 135 140Tyr Phe Ile Asp Val Leu Met Lys Lys Phe Glu Tyr Ser Pro Ser Lys145 150 155 160Val His Leu Ile Gly His Ser Leu Gly Ala His Leu Ala Gly Glu Ala165 170 175Gly Ser Arg Ile Pro Gly Leu Gly Arg Ile Thr Gly Lys His Ala Leu180 185 190Gln Leu Gly Leu Glu Cys Ala Thr Glu Gly Tyr Leu Leu Ser Ala Thr195 200 205Leu Ala Asn Asn Val Asn Phe Val Asp Thr Asn His Met Asp Ala Thr210 215 220Pro Ile Ile Pro Gln Trp Met Arg Gly Thr Ser Gly Thr Ser Asn Pro225 230 235 240Leu Pro Val Thr Ser Ser Leu Cys Leu Trp Leu Ala Asp Leu Gly Ser245 250 255Val Ser Leu Val Cys Leu Trp Pro Glu Met Ala Ser Phe Phe Asp Cys260 265 270Asn His Ala Arg Ser Tyr Gln Phe Tyr Ala Glu Ser Ile Leu Asn Pro275 280 285Asp Ala Phe Ile Ala Tyr Pro Cys Arg Ser Tyr Thr Ser Phe Lys Ala290 295 300Gly Asn Cys Phe Phe Cys Ser Lys Glu Gly Cys Pro Thr Met Gly His305 310 315 320Phe Ala Asp Arg Phe His Phe Lys Asn Met Lys Thr Asn Gly Ser His325 330 335Tyr Phe Leu Asn Thr Gly Ser Leu Ser Pro Phe Ala Arg Trp Arg His340 345 350Lys Leu Ser Val Lys Leu Ser Gly Ser Glu Val Thr Gln Gly Thr Val355 360 365Phe Leu Arg Val Gly Gly Ala Val Arg Lys Thr Gly Glu Phe Ala Ile370 375 380Val Ser Gly Lys Leu Glu Pro Gly Met Thr Tyr Thr Lys Leu Ile Asp385 390 395 400Ala Asp Val Asn Val Gly Asn Ile Thr Ser Val Gln Phe Ile Trp Lys405 410 415Lys His Leu Phe Glu Asp Ser Gln Asn Lys Leu Gly Ala Glu Met Val420 425 430Ile Asn Thr Ser Gly Lys Tyr Gly Tyr Lys Ser Thr Phe Cys Ser Gln435 440 445Asp Ile Met Gly Pro Asn Ile Leu Gln Asn Leu Lys Pro Cys450 455 460<210>69<211>255<212>PRT<213>人(Homo sapiens)<400>69Met Val Leu Leu Leu Val Ile Leu Ile Pro Val Leu Val Ser Ser Ala1 5 10 15Gly Thr Ser Ala His Tyr Glu Met Leu Gly Thr Cys Arg Met Val Cys20 25 30Asp Pro Tyr Gly Gly Thr Lys Ala Pro Ser Thr Ala Ala Thr Pro Asp35 40 45Arg Gly Leu Met Gln Ser Leu Pro Thr Phe Ile Gln Gly Pro Lys Gly50 55 60Glu Ala Gly Arg Pro Gly Lys Ala Gly Pro Arg Gly Pro Pro Gly Glu65 70 75 80Pro Gly Pro Pro Gly Pro Met Gly Pro Pro Gly Glu Lys Gly Glu Pro85 90 95Gly Arg Gln Gly Leu Pro Gly Pro Pro Gly Ala Pro Gly Leu Asn Ala100 105 110Ala Gly Ala Ile Ser Ala Ala Thr Tyr Ser Thr Gly Pro Lys Ile Ala115 120 125Phe Tyr Ala Gly Leu Lys Arg Gln His Glu Gly Tyr Glu Val Leu Lys130 135 140Phe Asp Asp Val Val Thr Asn Leu Gly Asn His Tyr Asp Pro Thr Thr145 150 155 160Gly Lys Phe Thr Cys Ser Ile Pro Gly Ile Tyr Phe Phe Thr Tyr His165 170 175Val Leu Met Arg Gly Gly Asp Gly Thr Ser Met Trp Ala Asp Leu Cys180 185 190Lys Asn Asn Gln Val Arg Ala Ser Ala Ile Ala Gln Asp Ala Asp Gln195 200 205Asn Tyr Asp Tyr Ala Ser Asn Ser Val Val Leu His Leu Glu Pro Gly210 215 220Asp Glu Val Tyr Ile Lys Leu Asp Gly Gly Lys Ala His Gly Gly Asn225 230 235 240Asn Asn Lys Tyr Ser Thr Phe Ser Gly Phe Ile Ile Tyr Ala Asp245 250255<210>70<211>784<212>PRT<213>人(Homo sapiens)<400>70Met Glu Gly Asp Gly Gly Thr Pro Trp Ala Leu Ala Leu Leu Arg Thr1 5 10 15Phe Asp Ala Gly Glu Phe Thr Gly Trp Glu Lys Val Gly Ser Gly Gly20 25 30Phe Gly Gln Val Tyr Lys Val Arg His Val His Trp Lys Thr Trp Leu35 40 45Ala Ile Lys Cys Ser Pro Ser Leu His Val Asp Asp Arg Glu Arg Met50 55 60Glu Leu Leu Glu Glu Ala Lys Lys Met Glu Met Ala Lys Phe Arg Tyr65 70 75 80Ile Leu Pro Val Tyr Gly Ile Cys Arg Glu Pro Val Gly Leu Val Met85 90 95Glu Tyr Met Glu Thr Gly Ser Leu Glu Lys Leu Leu Ala Ser Glu Pro100 105 110Leu Pro Trp Asp Leu Arg Phe Arg Ile Ile His Glu Thr Ala Val Gly115 120 125Met Asn Phe Leu His Cys Met Ala Pro Pro Leu Leu His Leu Asp Leu130 135 140Lys Pro Ala Asn Ile Leu Leu Asp Ala His Tyr His Val Lys Ile Ser145 150 155 160Asp Phe Gly Leu Ala Lys Cys Asn Gly Leu Ser His Ser His Asp Leu165 170 175Ser Met Asp Gly Leu Phe Gly Thr Ile Ala Tyr Leu Pro Pro Glu Arg180 185 190Ile Arg Glu Lys Ser Arg Leu Phe Asp Thr Lys His Asp Val Tyr Ser195 200 205Phe Ala Ile Val Ile Trp Gly Val Leu Thr Gln Lys Lys Pro Phe Ala210 215 220Asp Glu Lys Asn Ile Leu His Ile Met Val Lys Val Val Lys Gly His225 230 235 240Arg Pro Glu Leu Pro Pro Val Cys Arg Ala Arg Pro Arg Ala Cys Ser245 250 255His Leu Ile Arg Leu Met Gln Arg Cys Trp Gln Gly Asp Pro Arg Val260 265 270Arg Pro Thr Phe Gln Glu Ile Thr Ser Glu Thr Glu Asp Leu Cys Glu275 280 285Lys Pro Asp Asp Glu Val Lys Glu Thr Ala His Asp Leu Asp Val Lys290 295 300Ser Pro Pro Glu Pro Arg Ser Glu Val Val Pro Ala Arg Leu Lys Arg305 310 315 320Ala Ser Ala Pro Thr Phe Asp Asn Asp Tyr Ser Leu Ser Glu Leu Leu325 330 335Ser Gln Leu Asp Ser Gly Val Ser Gln Ala Val Glu Gly Pro Glu Glu340 345 350Leu Ser Arg Ser Ser Ser Glu Ser Lys Leu Pro Ser Ser Gly Ser Gly355 360 365Lys Arg Leu Ser Gly Val Ser Ser Val Asp Ser Ala Phe Ser Ser Arg370 375 380Gly Ser Leu Ser Leu Ser Phe Glu Arg Glu Pro Ser Thr Ser Asp Leu385 390 395 400Gly Thr Thr Asp Val Gln Lys Lys Lys Leu Val Asp Ala Ile Val Ser405 410 415Gly Asp Thr Ser Lys Leu Met Lys Ile Leu Gln Pro Gln Asp Val Asp420 425 430Leu Ala Leu Asp Ser Gly Ala Ser Leu Leu His Leu Ala Val Glu Ala435 440 445Gly Gln Glu Glu Cys Ala Lys Trp Leu Leu Leu Asn Asn Ala Asn Pro450 455 460Asn Leu Ser Asn Arg Arg Gly Ser Thr Pro Leu His Met Ala Val Glu465 470 475 480Arg Arg Val Arg Gly Val Val Glu Leu Leu Leu Ala Arg Lys Ile Ser485 490 495Val Asn Ala Lys Asp Glu Asp Gln Trp Thr Ala Leu His Phe Ala Ala500 505 510Gln Asn Gly Asp Glu Ser Ser Thr Arg Leu Leu Leu Glu Lys Asn Ala515 520 525Ser Val Asn Glu Val Asp Phe Glu Gly Arg Thr Pro Met His Val Ala530 535 540Cys Gln His Gly Gln Glu Asn Ile Val Arg Ile Leu Leu Arg Arg Gly545 550 555 560Val Asp Val Ser Leu Gln Gly Lys Asp Ala Trp Leu Pro Leu His Tyr565 570 575Ala Ala Trp Gln Gly His Leu Pro Ile Val Lys Leu Leu Ala Lys Gln580 585 590Pro Gly Val Ser Val Asn Ala Gln Thr Leu Asp Gly Arg Thr Pro Leu595 600 605His Leu Ala Ala Gln Arg Gly His Tyr Arg Val Ala Arg Ile Leu Ile610 615 620Asp Leu Cys Ser Asp Val Asn Val Cys Ser Leu Leu Ala Gln Thr Pro625 630 635 640Leu His Val Ala Ala Glu Thr Gly His Thr Ser Thr Ala Arg Leu Leu645 650 655Leu His Arg Gly Ala Gly Lys Glu Ala Met Thr Ser Asp Gly Tyr Thr660 665 670Ala Leu His Leu Ala Ala Arg Asn Gly His Leu Ala Thr Val Lys Leu675 680 685Leu Val Glu Glu Lys Ala Asp Val Leu Ala Arg Gly Pro Leu Asn Gln690 695 700Thr Ala Leu His Leu Ala Ala Ala His Gly His Ser Glu Val Val Glu705 710 715 720Glu Leu Val Ser Ala Asp Val Ile Asp Leu Phe Asp Glu Gln Gly Leu725 730 735Ser Ala Leu His Leu Ala Ala Gln Gly Arg His Ala Gln Thr Val Glu740 745 750Thr Leu Leu Arg His Gly Ala His Ile Asn Leu Gln Ser Leu Lys Phe755 760 765Gln Gly Gly His Gly Pro Ala Ala Thr Leu Leu Arg Arg Ser Lys Thr770 775 780<210>71<211>252<212>PRT<213>人(Homo sapiens)<400>71Met Ala Ala Pro Ala Leu Leu Leu Leu Ala Leu Leu Leu Pro Val Gly1 5 10 15Ala Trp Pro Gly Leu Pro Arg Arg Pro Cys Val His Cys Cys Arg Pro20 25 30Ala Trp Pro Pro Gly Pro Tyr Ala Arg Val Ser Asp Arg Asp Leu Trp35 40 45Arg Gly Asp Leu Trp Arg Gly Leu Pro Arg Val Arg Pro Thr Ile Asp50 55 60Ile Glu Ile Leu Lys Gly Glu Lys Gly Glu Ala Gly Val Arg Gly Arg65 70 75 80Ala Gly Arg Ser Gly Lys Glu Gly Pro Pro Gly Ala Arg Gly Leu Gln85 90 95Gly Arg Arg Gly Gln Lys Gly Gln Val Gly Pro Pro Gly Ala Ala Cys100 105 110Arg Arg Ala Tyr Ala Ala Phe Ser Val Gly Arg Arg Glu Gly Leu His115 120 125Ser Ser Asp His Phe Gln Ala Val Pro Phe Asp Thr Glu Leu Val Asn130 135 140Leu Asp Gly Ala Phe Asp Leu Ala Ala Gly Arg Phe Leu Cys Thr Val145 150 155 160Pro Gly Val Tyr Phe Leu Ser Leu Asn Val His Thr Trp Asn Tyr Lys165 170 175Glu Thr Tyr Leu His Ile Met Leu Asn Arg Arg Pro Ala Ala Val Leu180 185 190Tyr Ala Gln Pro Ser Glu Arg Ser Val Met Gln Ala Gln Ser Leu Met195 200 205Leu Leu Leu Ala Ala Gly Asp Ala Val Trp Val Arg Met Phe Gln Arg210 215 220Asp Arg Asp Asn Ala Ile Tyr Gly Glu His Gly Asp Leu Tyr Ile Thr225 230 235 240Phe Ser Gly His Leu Val Lys Pro Ala Ala Glu Leu245 250<210>72<211>593<212>PRT<213>人(Homo sapiens)<400>72Met Pro Ser Ser Leu Phe Ala Asp Leu Glu Arg Asn Gly Ser Gly Gly1 5 10 15Gly Gly Gly Gly Ser Ser Gly Gly Gly Glu Thr Leu Asp Asp Gln Arg20 25 30Ala Leu Gln Leu Ala Leu Asp Gln Leu Ser Leu Leu Gly Leu Asp Ser35 40 45Asp Glu Gly Ala Ser Leu Tyr Asp Ser Glu Pro Arg Lys Lys Ser Val50 55 60Asn Met Thr Glu Cys Val Pro Val Pro Ser Ser Glu His Val Ala Glu65 70 75 80Ile Val Gly Arg Gln Gly Arg Ser Arg Arg Asp Gly Glu Leu Asp Pro85 90 95Ser Gly Ile Ser Pro Asp Asp Phe Ser Gly Ile Leu Gly Phe Gly Ser100 105 110Gly Arg Leu Gln Ser Leu Gly Glu Gly Gln Ala Ala Asn Gly Leu Phe115 120 125Leu Glu Arg Leu Ala Gly Gly Ile Arg Cys Pro Ala Arg Gly Ala Ala130 135 140Arg Gly Cys Lys Ile Lys Ala Leu Arg Ala Lys Thr Asn Thr Tyr Ile145 150 155 160Lys Thr Pro Val Arg Gly Glu Glu Pro Val Phe Val Val Thr Gly Arg165 170 175Lys Glu Asp Val Ala Met Ala Arg Arg Glu Ile Ile Ser Ala Ala Glu180 185 190His Phe Ser Met Ile Arg Ala Ser Arg Asn Lys Asn Thr Ala Leu Asn195 200 205Gly Ala Val Pro Gly Pro Pro Asn Leu Pro Gly Gln Thr Thr Ile Gln210 215 220Val Arg Val Pro Tyr Arg Val Val Gly Leu Val Val Gly Pro Lys Gly225 230 235 240Ala Thr Ile Lys Arg Ile Gln Gln Gln Thr His Thr Tyr Ile Val Thr245 250 255Pro Ser Arg Asp Lys Glu Pro Val Phe Glu Val Thr Gly Met Pro Glu260 265 270Asn Val Asp Arg Ala Arg Glu Glu Ile Glu Ala His Ile Ala Leu Arg275 280 285Thr Gly Gly Ile Ile Glu Leu Thr Asp Glu Asn Asp Phe His Ala Asn290 295 300Gly Thr Asp Val Gly Phe Asp Leu His His Gly Ser Gly Gly Ala Ser305 310 315 320Thr Asp Ser Tyr Phe Gly Gly Gly Thr Ser Ser Ser Ala Ala Ala Thr325 330 335Gln Arg Leu Ala Asp Tyr Ser Pro Pro Ser Pro Ala Leu Ser Phe Ala340 345 350His Asn Gly Asn Asn Asn Asn Asn Gly Asn Gly Tyr Thr Tyr Thr Ala355 360 365Gly Gly Glu Ala Ser Val Pro Ser Pro Asp Gly Cys Pro Glu Leu Gln370 375 380Pro Thr Phe Asp Pro Ala Pro Ala Pro Pro Pro Gly Ala Pro Leu Ile385 390 395 400Trp Ala Gln Phe Glu Arg Ser Pro Gly Gly Gly Pro Ala Ala Pro Val405 410 415Ser Ser Ser Cys Ser Ser Ser Ala Ser Ser Ser Ala Ser Ser Ser Ser420 425 430Val Val Phe Pro Gly Gly Gly Ala Ser Ala Pro Ser Asn Ala Asn Leu435 440 445Gly Leu Leu Val His Arg Arg Leu His Pro Gly Thr Ser Cys Pro Arg450 455 460Leu Ser Pro Pro Leu His Met Ala Pro Gly Ala Gly Glu His His Leu465 470 475 480Ala Arg Arg Val Arg Ser Asp Pro Gly Gly Gly Gly Leu Ala Tyr Ala485 490 495Ala Tyr Ala Asn Gly Leu Gly Ala Gln Leu Pro Gly Leu Gln Pro Ser500 505 510Asp Thr Ser Gly Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser515 520 525Ser Ser Ser Ser Gly Leu Arg Arg Lys Gly Ser Arg Asp Cys Ser Val530 535 540Cys Phe Glu Ser Glu Val Ile Ala Ala Leu Val Pro Cys Gly His Asn545 550 555 560Leu Phe Cys Met Glu Cys Ala Asn Arg Ile Cys Glu Lys Ser Glu Pro565 570 575Glu Cys Pro Val Cys His Thr Ala Val Thr Gln Ala Ile Arg Ile Phe580 585 590Ser<210>73<211>472<212>PRT<213>人(Homo sapiens)<400>73Met Pro Ser Ser Leu Phe Ala Asp Leu Glu Arg Asn Gly Ser Gly Gly1 5 10 15Gly Gly Gly Gly Ser Ser Gly Gly Gly Glu Thr Leu Asp Asp Gln Arg20 25 30Ala Leu Gln Leu Ala Leu Asp Gln Leu Ser Leu Leu Gly Leu Asp Ser35 40 45Asp Glu Gly Ala Ser Leu Tyr Asp Ser Glu Pro Arg Lys Lys Ser Val50 55 60Asn Met Thr Glu Cys Val Pro Val Pro Ser Ser Glu His Val Ala Glu65 70 75 80Ile Val Gly Arg Gln Gly Cys Lys Ile Lys Ala Leu Arg Ala Lys Thr85 90 95Asn Thr Tyr Ile Lys Thr Pro Val Arg Gly Glu Glu Pro Val Phe Val100 105 110Val Thr Gly Arg Lys Glu Asp Val Ala Met Ala Arg Arg Glu Ile Ile115 120 125Ser Ala Ala Glu His Phe Ser Met Ile Arg Ala Ser Arg Asn Lys Asn130 135 140Thr Ala Leu Asn Gly Ala Val Pro Gly Pro Pro Asn Leu Pro Gly Gln145 150 155 160Thr Thr Ile Gln Val Arg Val Pro Tyr Arg Val Val Gly Leu Val Val165 170 175Gly Pro Lys Gly Ala Thr Ile Lys Arg Ile Gln Gln Gln Thr His Thr180 185 190Tyr Ile Val Thr Pro Ser Arg Asp Lys Glu Pro Val Phe Glu Val Thr195 200 205Gly Met Pro Glu Asn Val Asp Arg Ala Arg Glu Glu Ile Glu Ala His210 215 220Ile Ala Leu Arg Thr Gly Gly Ile Ile Glu Leu Thr Asp Glu Asn Asp225 230 235 240Phe His Ala Asn Gly Thr Asp Val Gly Phe Asp Leu His His Gly Ser245 250 255Gly Gly Ser Gly Pro Gly Ser Leu Trp Ser Lys Pro Thr Pro Ser Ile260 265 270Thr Pro Thr Pro Gly Arg Lys Pro Phe Ser Ser Tyr Arg Asn Asp Ser275 280 285Ser Ser Ser Leu Gly Ser Ala Ser Thr Asp Ser Tyr Phe Gly Gly Gly290 295 300Thr Ser Ser Ser Ala Ala Ala Thr Gln Arg Leu Ala Asp Tyr Ser Pro305 310 315 320Ala Pro Ser Asn Ala Asn Leu Gly Leu Leu Val His Arg Arg Leu His325 330 335Pro Gly Thr Ser Cys Pro Arg Leu Ser Pro Pro Leu His Met Ala Pro340 345 350Gly Ala Gly Glu His His Leu Ala Arg Arg Val Arg Ser Asp Pro Gly355 360 365Gly Gly Gly Leu Ala Tyr Ala Ala Tyr Ala Asn Gly Leu Gly Ala Gln370 375 380Leu Pro Gly Leu Gln Pro Ser Asp Thr Ser Gly Ser Ser Ser Ser Ser385 390 395 400Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Gly Leu Arg Arg Lys405 410 415Gly Ser Arg Asp Cys Ser Val Cys Phe Glu Ser Glu Val Ile Ala Ala420 425 430Leu Val Pro Cys Gly His Asn Leu Phe Cys Met Glu Cys Ala Asn Arg435 440 445Ile Cys Glu Lys Ser Glu Pro Glu Cys Pro Val Cys His Thr Ala Val450 455 460Thr Gln Ala Ile Arg Ile Phe Ser465 470<210>74<211>607<212>PRT<213>人(Homo sapiens)<400>74Met Trp Gly Leu Val Arg Leu Leu Leu Ala Trp Leu Gly Gly Trp Gly1 5 10 15Cys Met Gly Arg Leu Ala Ala Pro Ala Arg Ala Trp Ala Gly Ser Arg20 25 30Glu His Pro Gly Pro Ala Leu Leu Arg Thr Arg Arg Ser Trp Val Trp35 40 45Asn Gln Phe Phe Val Ile Glu Glu Tyr Ala Gly Pro Glu Pro Val Leu50 55 60Ile Gly Lys Leu His Ser Asp Val Asp Arg Gly Glu Gly Arg Thr Lys65 70 75 80Tyr Leu Leu Thr Gly Glu Gly Ala Gly Thr Val Phe Val Ile Asp Glu
85 90 95Ala Thr Gly Asn Ile His Val Thr Lys Ser Leu Asp Arg Glu Glu Lys100 105 110Ala Gln Tyr Val Leu Leu Ala Gln Ala Val Asp Arg Ala Ser Asn Arg115 120 125Pro Leu Glu Pro Pro Ser Glu Phe Ile Ile Lys Val Gln Asp Ile Asn130 135 140Asp Asn Pro Pro Ile Phe Pro Leu Gly Pro Tyr His Ala Thr Val Pro145 150 155 160Glu Met Ser Asn Val Gly Thr Ser Val Ile Gln Val Thr Ala His Asp165 170 175Ala Asp Asp Pro Ser Tyr Gly Asn Ser Ala Lys Leu Val Tyr Thr Val180 185 190Leu Asp Gly Leu Pro Phe Phe Ser Val Asp Pro Gln Thr Gly Val Val195 200 205Arg Thr Ala Ile Pro Asn Met Asp Arg Glu Thr Gln Glu Glu Phe Leu210 215 220Val Val Ile Gln Ala Lys Asp Met Gly Gly His Met Gly Gly Leu Ser225 230 235 240Gly Ser Thr Thr Val Thr Val Thr Leu Ser Asp Val Asn Asp Asn Pro245 250 255Pro Lys Phe Pro Gln Ser Leu Tyr Gln Phe Ser Val Val Glu Thr Ala260 265 270Gly Pro Gly Thr Leu Val Gly Arg Leu Arg Ala Gln Asp Pro Asp Leu275 280 285Gly Asp Asn Ala Leu Met Ala Tyr Ser Ile Leu Asp Gly Glu Gly Ser290 295 300Glu Ala Phe Ser Ile Ser Thr Asp Leu Gln Gly Arg Asp Gly Leu Leu305 310 315 320Thr Val Arg Lys Pro Leu Asp Phe Glu Ser Gln Arg Ser Tyr Ser Phe325 330 335Arg Val Glu Ala Thr Asn Thr Leu Ile Asp Pro Ala Tyr Leu Arg Arg340 345 350Gly Pro Phe Lys Asp Val Ala Ser Val Arg Val Ala Val Gln Asp Ala355 360 365Pro Glu Pro Pro Ala Phe Thr Gln Ala Ala Tyr His Leu Thr Val Pro370 375 380Glu Asn Lys Ala Pro Gly Thr Leu Val Gly Gln Ile Ser Ala Ala Asp385 390 395 400Leu Asp Ser Pro Ala Ser Pro Ile Arg Tyr Ser Ile Leu Pro His Ser405 410 415Asp Pro Glu Arg Cys Phe Ser Ile Gln Pro Glu Glu Gly Thr Ile His420 425 430Thr Ala Ala Pro Leu Asp Arg Glu Ala Arg Ala Trp His Asn Leu Thr435 440 445Val Leu Ala Thr Glu Leu Val Pro Tyr Thr Pro Ala Tyr Ala Ser Gly450 455 460Ala Pro Pro Pro Phe Cys Leu His Thr Ala Tyr Glu Asn Cys Pro Cys465 470 475 480Ile Cys Gly Tyr Leu Asn Val Ser Val Lys Ala Tyr Met Asn Val His485 490 495Met Trp Ala Met Val Leu Val Phe Ala Glu His Lys Gly Gly Gly Arg500 505 510Gly Pro Gly Arg Gln Ala Val Asp Gly Gln Lys Gln Ser Thr Arg Trp515 520 525Glu Leu Ser Gln Asn Cys Asn Tyr Leu Pro Lys Ser Arg Glu Gly Val530 535 540His Pro Gly Thr Ser Met Arg Ala Gln Ala Ser Gln Leu Gln Gly Ser545 550 555 560Arg Gly Thr His Arg Asn Cys Thr Arg Ile Ala Cys His Thr Arg Val565 570 575Asn Pro Ile Leu Tyr His Ser Pro Thr Pro Gly His Arg Thr Thr Tyr580 585 590Thr Cys Gly His Glu Tyr Ala Pro Ser Tyr Ala Glu Ser Asn Thr595 600 605<210>75<211>781<212>PRT<213>人(Homo sapiens)<400>75Met Trp Gly Leu Val Arg Leu Leu Leu Ala Trp Leu Gly Gly Trp Gly1 5 10 15Cys Met Gly Arg Leu Ala Ala Pro Ala Arg Ala Trp Ala Gly Ser Arg20 25 30Glu His Pro Gly Pro Ala Leu Leu Arg Thr Arg Arg Ser Trp Val Trp35 40 45Asn Gln Phe Phe Val Ile Glu Glu Tyr Ala Gly Pro Glu Pro Val Leu50 55 60Ile Gly Lys Leu His Ser Asp Val Asp Arg Gly Glu Gly Arg Thr Lys65 70 75 80Tyr Leu Leu Thr Gly Glu Gly Ala Gly Thr Val Phe Val Ile Asp Glu85 90 95Ala Thr Gly Asn Ile His Val Thr Lys Ser Leu Asp Arg Glu Glu Lys100 105 110Ala Gln Tyr Val Leu Leu Ala Gln Ala Val Asp Arg Ala Ser Asn Arg115 120 125Pro Leu Glu Pro Pro Ser Glu Phe Ile Ile Lys Val Gln Asp Ile Asn130 135 140Asp Asn Pro Pro Ile Phe Pro Leu Gly Pro Tyr His Ala Thr Val Pro145 150 155 160Glu Met Ser Asn Val Gly Thr Ser Val Ile Gln Val Thr Ala His Asp165 170 175Ala Asp Asp Pro Ser Tyr Gly Asn Ser Ala Lys Leu Val Tyr Thr Val180 185 190Leu Asp Gly Leu Pro Phe Phe Ser Val Asp Pro Gln Thr Gly Val Val195 200 205Arg Thr Ala Ile Pro Asn Met Asp Arg Glu Thr Gln Glu Glu Phe Leu210 215 220Val Val Ile Gln Ala Lys Asp Met Gly Gly His Met Gly Gly Leu Ser225 230 235 240Gly Ser Thr Thr Val Thr Val Thr Leu Ser Asp Val Asn Asp Asn Pro245 250 255Pro Lys Phe Pro Gln Ser Leu Tyr Gln Phe Ser Val Val Glu Thr Ala260 265 270Gly Pro Gly Thr Leu Val Gly Arg Leu Arg Ala Gln Asp Pro Asp Leu275 280 285Gly Asp Asn Ala Leu Met Ala Tyr Ser Ile Leu Asp Gly Glu Gly Ser290 295 300Glu Ala Phe Ser Ile Ser Thr Asp Leu Gln Gly Arg Asp Gly Leu Leu305 310 315 320Thr Val Arg Lys Pro Leu Asp Phe Glu Ser Gln Arg Ser Tyr Ser Phe325 330 335Arg Val Glu Ala Thr Asn Thr Leu Ile Asp Pro Ala Tyr Leu Arg Arg340 345 350Gly Pro Phe Lys Asp Val Ala Ser Val Arg Val Ala Val Gln Asp Ala355 360 365Pro Glu Pro Pro Ala Phe Thr Gln Ala Ala Tyr His Leu Thr Val Pro370 375 380Glu Asn Lys Ala Pro Gly Thr Leu Val Gly Gln Ile Ser Ala Ala Asp385 390 395 400Leu Asp Ser Pro Ala Ser Pro Ile Arg Tyr Ser Ile Leu Pro His Ser405 410 415Asp Pro Glu Arg Cys Phe Ser Ile Gln Pro Glu Glu Gly Thr Ile His420 425 430Thr Ala Ala Pro Leu Asp Arg Glu Ala Arg Ala Trp His Asn Leu Thr435 440 445Val Leu Ala Thr Glu Leu Asp Ser Ser Ala Gln Ala Ser Arg Val Gln450 455 460Val Ala Ile Gln Thr Leu Asp Glu Asn Asp Asn Ala Pro Gln Leu Ala465 470 475 480Glu Pro Tyr Asp Thr Phe Val Cys Asp Ser Ala Ala Pro Gly Gln Leu485 490 495Ile Gln Val Ile Arg Ala Leu Asp Arg Asp Glu Val Gly Asn Ser Ser500 505 510His Val Ser Phe Gln Gly Pro Leu Gly Pro Asp Ala Asn Phe Thr Val515 520 525Gln Asp Asn Arg Asp Gly Ser Ala Ser Leu Leu Leu Pro Ser Arg Pro530 535 540Ala Pro Pro Arg His Ala Pro Tyr Leu Val Pro Ile Glu Leu Trp Asp545 550 555 560Trp Gly Gln Pro Ala Leu Ser Ser Thr Ala Thr Val Thr Val Ser Val565 570 575Cys Arg Cys Gln Pro Asp Gly Ser Val Ala Ser Cys Trp Pro Glu Ala580 585 590His Leu Ser Ala Ala Gly Leu Ser Thr Gly Ala Leu Leu Ala Ile Ile595 600 605Thr Cys Val Gly Ala Leu Leu Ala Leu Val Val Leu Phe Val Ala Leu610 615 620Arg Arg Gln Lys Gln Glu Ala Leu Met Val Leu Glu Glu Glu Asp Val625 630 635 640Arg Glu Asn Ile Ile Thr Tyr Asp Asp Glu Gly Gly Gly Glu Glu Asp645 650 655Thr Glu Ala Phe Asp Ile Thr Ala Leu Gln Asn Pro Asp Gly Ala Ala660 665 670Pro Pro Ala Pro Gly Pro Pro Ala Arg Arg Asp Val Leu Pro Arg Ala675 680 685Arg Val Ser Arg Gln Pro Arg Pro Pro Gly Pro Ala Asp Val Ala Gln690 695 700Leu Leu Ala Leu Arg Leu Arg Glu Ala Asp Glu Asp Pro Gly Val Pro705 710 715 720Pro Tyr Asp Ser Val Gln Val Tyr Gly Tyr Glu Gly Arg Gly Ser Ser725 730 735Cys Gly Ser Leu Ser Ser Leu Gly Ser Gly Ser Glu Ala Gly Gly Ala740 745 750Pro Gly Pro Ala Glu Pro Leu Asp Asp Trp Gly Pro Leu Phe Arg Thr755 760 765Leu Ala Glu Leu Tyr Gly Ala Lys Glu Pro Pro Ala Pro770 775 780<210>76<211>640<212>PRT<213>人(Homo sapiens)<400>76Met Ala Arg Gly His Tyr Ile Tyr Val Asp Thr Ser Phe Gly Lys Gln1 5 10 15Gly Glu Lys Ala Val Leu Leu Ser Pro Asp Leu Gln Ala Glu Glu Trp20 25 30Ser Cys Leu Arg Leu Val Tyr Gln Ile Thr Thr Ser Ser Glu Ser Leu35 40 45Ser Asp Pro Ser Gln Leu Asn Leu Tyr Met Arg Phe Glu Asp Glu Ser50 55 60Phe Asp Arg Leu Leu Trp Ser Ala Lys Glu Pro Ser Asp Ser Trp Leu65 70 75 80Ile Ala Ser Leu Asp Leu Gln Asn Ser Ser Lys Lys Phe Lys Ile Leu85 90 95Ile Glu Gly Val Leu Gly Gln Gly Asn Thr Ala Ser Ile Ala Leu Phe100 105 110Glu Ile Lys Met Thr Thr Gly Tyr Cys Ile Glu Cys Asp Phe Glu Glu115 120 125Asn His Leu Cys Gly Phe Val Asn Arg Trp Asn Pro Asn Val Asn Trp130 135 140Phe Val Gly Gly Gly Ser Ile Arg Asn Val His Ser Ile Leu Pro Gln145 150 155 160Asp His Thr Phe Lys Ser Glu Leu Gly His Tyr Met Tyr Val Asp Ser165 170 175Val Tyr Val Lys His Phe Gln Glu Val Ala Gln Leu Ile Ser Pro Leu180 185 190Thr Thr Ala Pro Met Ala Gly Cys Leu Ser Phe Tyr Tyr Gln Ile Gln195 200 205Gln Gly Asn Asp Asn Val Phe Ser Leu Tyr Thr Arg Asp Val Ala Gly210 215 220Leu Tyr Glu Glu Ile Trp Lys Ala Asp Arg Pro Gly Asn Ala Ala Trp225 230 235 240Asn Leu Ala Glu Val Glu Phe Thr Cys His Phe Pro Leu Gln Val Ile245 250 255Phe Glu Val Ala Phe Asn Gly Pro Lys Gly Gly Tyr Val Ala Leu Asp260 265 270Asp Ile Ser Phe Ser Pro Val His Cys Gln Asn Gln Thr Glu Leu Leu275 280 285Phe Ser Ala Val Glu Ala Ser Cys Asn Phe Glu Gln Asp Leu Cys Asn290 295 300Phe Tyr Gln Asp Lys Glu Gly Pro Gly Trp Thr Arg Val Lys Val Lys305 310 315 320Pro Asn Met Tyr Arg Ala Gly Asp His Thr Thr Gly Leu Gly Tyr Tyr325 330 335Leu Leu Ala Asn Thr Lys Phe Thr Ser Gln Pro Gly Tyr Ile Gly Arg340 345 350Leu Tyr Gly Pro Ser Leu Pro Gly Asn Leu Gln Tyr Cys Leu Arg Phe355 360 365His Tyr Ala Ile Tyr Gly Phe Leu Lys Met Ser Asp Thr Leu Ala Val370 375 380Tyr Ile Phe Glu Glu Asn His Val Val Gln Glu Lys Ile Trp Ser Val385 390 395 400Leu Glu Ser Pro Arg Gly Val Trp Met Gln Ala Glu Ile Thr Phe Lys405 410 415Lys Pro Met Pro Thr Lys Val Val Phe Met Ser Leu Cys Lys Ser Phe420 425 430Trp Asp Cys Gly Leu Val Ala Leu Asp Asp Ile Thr Ile Gln Leu Gly435 440 445Ser Cys Ser Ser Ser Glu Lys Leu Pro Pro Pro Pro Gly Glu Cys Thr450 455 460Phe Glu Gln Asp Glu Cys Thr Phe Thr Gln Glu Lys Arg Asn Arg Ser465 470 475 480Ser Trp His Arg Arg Arg Gly Glu Thr Pro Thr Ser Tyr Thr Gly Pro485 490 495Lys Gly Asp His Thr Thr Gly Val Gly Tyr Tyr Met Tyr Ile Glu Ala500 505 510Ser His Met Val Tyr Gly Gln Lys Ala Arg Leu Leu Ser Arg Pro Leu515 520 525Arg Gly Val Ser Gly Lys His Cys Leu Thr Phe Phe Tyr His Met Tyr530 535 540Gly Gly Gly Thr Gly Leu Leu Ser Val Tyr Leu Lys Lys Glu Glu Asp545 550 555 560Ser Glu Glu Ser Leu Leu Trp Arg Arg Arg Gly Glu Gln Ser Ile Ser565 570 575Trp Leu Arg Ala Leu Ile Glu Tyr Ser Cys Glu Arg Gln His Gln Ile580 585 590Ile Phe Glu Ala Ile Arg Gly Val Ser Ile Arg Ser Asp Ile Ala Ile595 600 605Asp Asp Val Lys Phe Gln Ala Gly Pro Cys Gly Glu Met Glu Asp Thr610 615 620Thr Gln Gln Ser Ser Gly Tyr Ser Glu Asp Leu Asn Glu Ile Glu Tyr625 630 635 640<210>77<211>686<212>PRT<213>人(Homo sapiens)<400>77Met Leu Leu Arg Gly Val Leu Leu Ala Leu Gln Ala Leu Gln Leu Ala1 5 10 15Gly Ala Leu Asp Leu Pro Ala Gly Ser Cys Ala Phe Glu Glu Ser Thr20 25 30Cys Gly Phe Asp Ser Val Leu Ala Ser Leu Pro Trp Ile Leu Asn Glu35 40 45Glu Gly His Tyr Ile Tyr Val Asp Thr Ser Phe Gly Lys Gln Gly Glu50 55 60Lys Ala Val Leu Leu Ser Pro Asp Leu Gln Ala Glu Glu Trp Ser Cys65 70 75 80Leu Arg Leu Val Tyr Gln Ile Thr Thr Ser Ser Glu Ser Leu Ser Asp85 90 95Pro Ser Gln Leu Asn Leu Tyr Met Arg Phe Glu Asp Glu Ser Phe Asp100 105 110Arg Leu Leu Trp Ser Ala Lys Glu Pro Ser Asp Ser Trp Leu Ile Ala115 120 125Ser Leu Asp Leu Gln Asn Ser Ser Lys Lys Phe Lys Ile Leu Ile Glu130 135 140Gly Val Leu Gly Gln Gly Asn Thr Ala Ser Ile Ala Leu Phe Glu Ile145 150 155 160Lys Met Thr Thr Gly Tyr Cys Ile Glu Cys Asp Phe Glu Glu Asn His165 170 175Leu Cys Gly Phe Val Asn Arg Trp Asn Pro Asn Val Asn Trp Phe Val180 185 190Gly Gly Gly Ser Ile Arg Asn Val His Ser Ile Leu Pro Gln Asp His195 200 205Thr Phe Lys Ser Glu Leu Gly His Tyr Met Tyr Val Asp Ser Val Tyr210 215 220Val Lys His Phe Gln Glu Val Ala Gln Leu Ile Ser Pro Leu Thr Thr225 230 235 240Ala Pro Met Ala Gly Cys Leu Ser Phe Tyr Tyr Gln Ile Gln Gln Gly
245 250 255Asn Asp Asn Val Phe Ser Leu Tyr Thr Arg Asp Val Ala Gly Leu Tyr260 265 270Glu Glu Ile Trp Lys Ala Asp Arg Pro Gly Asn Ala Ala Trp Asn Leu275 280 285Ala Glu Val Glu Phe Thr Cys His Phe Pro Leu Gln Val Ile Phe Glu290 295 300Val Ala Phe Asn Gly Pro Lys Gly Gly Tyr Val Ala Leu Asp Asp Ile305 310 315 320Ser Phe Ser Pro Val His Cys Gln Asn Gln Thr Glu Leu Leu Phe Ser325 330 335Ala Val Glu Ala Ser Cys Asn Phe Glu Gln Asp Leu Cys Asn Phe Tyr340 345 350Gln Asp Lys Glu Gly Pro Gly Trp Thr Arg Val Lys Val Lys Pro Asn355 360 365Met Tyr Arg Ala Gly Asp His Thr Thr Gly Leu Gly Tyr Tyr Leu Leu370 375 380Ala Asn Thr Lys Phe Thr Ser Gln Pro Gly Tyr Ile Gly Arg Leu Tyr385 390 395 400Gly Pro Ser Leu Pro Gly Asn Leu Gln Tyr Cys Leu Arg Phe His Tyr405 410 415Ala Ile Tyr Gly Phe Leu Lys Met Ser Asp Thr Leu Ala Val Tyr Ile420 425 430Phe Glu Glu Asn His Val Val Gln Glu Lys Ile Trp Ser Val Leu Glu435 440 445Ser Pro Arg Gly Val Trp Met Gln Ala Glu Ile Thr Phe Lys Lys Pro450 455 460Met Pro Thr Lys Val Val Phe Met Ser Leu Cys Lys Ser Phe Trp Asp465 470 475 480Cys Gly Leu Val Ala Leu Asp Asp Ile Thr Ile Gln Leu Gly Ser Cys485 490 495Ser Ser Ser Glu Lys Leu Pro Pro Pro Pro Gly Glu Cys Thr Phe Glu500 505 510Gln Asp Glu Cys Thr Phe Thr Gln Glu Lys Arg Asn Arg Ser Ser Trp515 520 525His Arg Arg Arg Gly Glu Thr Pro Thr Ser Tyr Thr Gly Pro Lys Gly530 535 540Asp His Thr Thr Gly Val Gly Tyr Tyr Met Tyr Ile Glu Ala Ser His545 550 555 560Met Val Tyr Gly Gln Lys Ala Arg Leu Leu Ser Arg Pro Leu Arg Gly565 570 575Val Ser Gly Lys His Cys Leu Thr Phe Phe Tyr His Met Tyr Gly Gly580 585 590Gly Thr Gly Leu Leu Ser Val Tyr Leu Lys Lys Glu Glu Asp Ser Glu595 600 605Glu Ser Leu Leu Trp Arg Arg Arg Gly Glu Gln Ser Ile Ser Trp Leu610 615 620Arg Ala Leu Ile Glu Tyr Ser Cys Glu Arg Gln His Gln Ile Ile Phe625 630 635 640Glu Ala Ile Arg Gly Val Ser Ile Arg Ser Asp Ile Ala Ile Asp Asp645 650 655Val Lys Phe Gln Ala Gly Pro Cys Gly Glu Met Glu Asp Thr Thr Gln660 665 670Gln Ser Ser Gly Tyr Ser Glu Asp Leu Asn Glu Ile Glu Tyr675 680 685<210>78<211>154<212>PRT
<213>人(Homo sapiens)<400>78Met Thr Leu Ser Pro Thr Gln Pro Pro Leu Phe His Leu Pro Tyr Val1 5 10 15Gln Lys Cys Phe Ile Pro Thr Val Glu Gln Leu Thr Leu Gly Ile Pro20 25 30Cys Gln Asn His Gly Glu Ile Asp His Gly Gln Asp Ile Phe Pro Ala35 40 45Glu Lys Leu Cys His Leu Gln Asp Cys Lys Val Asn Leu His Arg Ala50 55 60Ala Cys Gly Glu Cys Ile Val Ala Pro Lys Thr Ser Ser Phe Pro Tyr65 70 75 80Cys Gln Gly Thr Cys Leu Thr Leu Asn Ser Glu Leu His Gln Ser Asn85 90 95Phe Ala Leu Lys Val Cys Thr Ile Arg Gly Glu Cys Leu Leu Ile Cys100 105 110Ser Trp Leu Phe Gln Thr Cys Ser Pro Thr Lys Val Ile Leu Phe Ser115 120 125Leu Thr Val Gln Asp Asp Glu Arg Lys Met Ser Val His Cys Val Asn130 135 140Ala Ser Leu Ile Glu Lys Cys Gly Cys Ser145 150
權(quán)利要求
1.一種分離的多肽，該多肽選自(a)由包括表I中序列的多核苷酸編碼的分離多肽；(b)包括表I中多肽序列的分離多肽；和(c)表I中基因的多肽序列。
2.一種分離的多核苷酸，該多核苷酸選自(a)一種分離的多核苷酸，其中包括表I中的多核苷酸序列；(b)表I中基因的分離多核苷酸；(c)一種分離的多核苷酸，其中包括編碼表I中多肽的多核苷酸序列；(d)編碼表I中多肽的分離的多核苷酸序列；(e)一種多核苷酸，該多核苷酸是(a)到(d)中多核苷酸的RNA等價物；或者與上述分離的多核苷酸互補(bǔ)的多核苷酸序列。
3.一種表達(dá)載體，其中包括多核苷酸，該多核苷酸在所述表達(dá)載體出現(xiàn)在相容性宿主細(xì)胞中時能夠生成權(quán)利要求1中所述的多肽。
4.一種制備重組宿主細(xì)胞的方法，其中包括下述步驟將包含能生成權(quán)利要求1中所述多肽的多核苷酸的表達(dá)載體導(dǎo)入細(xì)胞從而使得所述宿主細(xì)胞能夠在合適的培養(yǎng)條件下生成所述的多肽。
5.一種用權(quán)利要求4所述方法制備而成的重組宿主細(xì)胞。
6.表達(dá)所述多肽的權(quán)利要求5中所述宿主細(xì)胞的細(xì)胞膜。
7.一種制備多肽的方法，其中包括將權(quán)利要求5中所述宿主細(xì)胞培養(yǎng)在足以制備出所述多肽的條件下，然后從培養(yǎng)基中回收所述多肽。
全文摘要
本發(fā)明公開了表I中所列基因的多肽和多核苷酸，以及用重組技術(shù)制備所述多肽的方法。本發(fā)明還公開了所列基因的多肽和多核苷酸用于診斷試驗(yàn)的方法。
文檔編號A61P1/00GK1439017SQ01811752
公開日2003年8月27日 申請日期2001年4月26日 優(yōu)先權(quán)日2000年4月27日
發(fā)明者潘卡杰·阿加沃爾, 保羅·R·默多克, 薩菲亞·K·里茲維, 蘭德爾·F·史密斯, 向朝英, 卡倫·S·卡布尼克, 賴英塔, 謝青 申請人:史密絲克萊恩比徹姆公司, 史密斯克萊·比奇曼公司