專利名稱：新型化合物的制作方法
技術(shù)領(lǐng)域：
本發(fā)明涉及新鑒定的多肽及編碼所述多肽的多核苷酸，它們在診斷中的應(yīng)用，以及它們在鑒定可能作為在治療有潛在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結(jié)合(下文往往統(tǒng)稱為分泌蛋白或分泌多肽)。
背景技術(shù)：
藥物發(fā)現(xiàn)方法由于涉及“功能基因組”學(xué)，即以基因組或基因為基礎(chǔ)的高流通量(high throughput)生物學(xué)，而正經(jīng)歷一場重大變革。這種方法作為將基因和基因產(chǎn)物鑒定為治療靶標(biāo)的手段，迅速取代了原來以“定位克隆”為基礎(chǔ)的方法。生物功能或遺傳疾病的表型得到鑒定，接著可根據(jù)其遺傳圖譜位置回溯到負(fù)責(zé)基因(responsible gene)。
功能基因組學(xué)在很大程度上依賴于高流通量DNA測序技術(shù)和各種生物信息學(xué)工具，以便從現(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。對鑒定和定性其它基因及其有關(guān)蛋白/多肽的需求一直都存在，這是藥物發(fā)現(xiàn)的靶標(biāo)。
那些天然分泌到血液、淋巴或其它體液中，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)。原因在于可以相對容易地將蛋白治療靶向它們的作用位置(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)胞質(zhì)的天然通道(除了胞吐作用，即蛇毒液中毒素侵入細(xì)胞的機(jī)制外)。因此，將蛋白治療物靶入細(xì)胞面臨著巨大困難。
分泌型及膜結(jié)合型蛋白包括但不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)，乳腺癌及結(jié)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、超過氧化物歧化酶、剪接體蛋白、7TM(跨膜)蛋白也稱為G-蛋白偶聯(lián)型受體、免疫球蛋白、絲氨酸蛋白酶的幾個家族(包括但不限于血液凝固級聯(lián)反應(yīng)的蛋白、消化酶)、脫氧核糖核酸酶I等。
FDA或外國機(jī)構(gòu)批準(zhǔn)基于分泌型蛋白或膜結(jié)合蛋白的治療物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，Genentech)、hyaulorindase(Wydase，Wyeth-Ayerst)，α鏈道酶(Pulmozyme\，Genentech)，Chymodiactin(chymopapain，Knoll)，糖腦苷酶(Ceredase，Genzyme)，鏈激酶(Kabikinase，Pharmacia)(Streptase，Astra)等。這表明分泌型及膜結(jié)合型蛋白質(zhì)作為治療靶標(biāo)已有確證的歷史。顯然，需要對其它能夠預(yù)防、減緩或糾正功能紊亂或疾病的分泌型及膜結(jié)合型蛋白質(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)腸癌及其它惡性腫瘤、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)育障礙、精神發(fā)育障礙或性發(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)致中風(fēng)(stroke)的那些功能紊亂)。本發(fā)明中含信號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中列出基因的具體多肽及多核苷酸，包括用于制備它們的重組材料和方法。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)明提供的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。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、功能和、或代謝的異常而引發(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公開的每個所附序列與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。
發(fā)明詳述第一方面，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的一種序列的多核苷酸編碼的分離的多肽，本發(fā)明中提到序列表中所列多核苷酸或多肽時，在序列表部分的序列列表中有相應(yīng)參照；(b)一種分離的多肽，該多肽包括與序列表中的一種多肽序列具有至少95％，96％，97％，98％，或99％同一性的多肽序列；(c)一種分離的多肽，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)序列表中列出的一種多肽序列；以及(f)一種分離的多肽，該多肽具有或包括與序列表所列的多肽序列之間的同一性指數(shù)(Indentity Index)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)明多肽據(jù)信是表II中基因家族的成員。因此根據(jù)表III和V中所列的理由，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)明多肽具有表I中基因的至少一種生物學(xué)活性。
本發(fā)明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。所述多肽可以是從參考多肽通過保守或非保守的插入、缺失及取代，或其任何組合變化而來。具體優(yōu)選的變體是那些以任意組合插入、取代或缺失了數(shù)個(如50～30、30～20、20～10、10～5、5～3、3～2、2～1個或1個)氨基酸的變體。
本發(fā)明多肽的優(yōu)選片段包括這樣的分離的多肽，該分離的多肽包括一種氨基酸序列，該序列具有來自序列表所列的一種氨基酸序列的至少30、50或100個連續(xù)氨基酸，或者該序列具有將序列表所列的一種氨基酸序列中截短或缺失至少30、50或100個連續(xù)氨基酸所得的氨基酸序列。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。還優(yōu)選在動物體，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)明多肽的片段制備相應(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，也可以是如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，或者在重組生產(chǎn)過程中用來保持穩(wěn)定的一段額外的氨基酸序列。
本發(fā)明多肽可以以任何適當(dāng)?shù)姆绞街苽洌缈梢詮奶烊粊碓捶蛛x，從含表達(dá)系統(tǒng)(見下文)的基因工程宿主細(xì)胞分離，或者例如使用自動肽合成儀化學(xué)合成，或者上述方法的組合。制備所述多肽的方法為本領(lǐng)域技術(shù)人員所熟知。
另一方面，本發(fā)明涉及表I中所列基因的多核苷酸。這些多核苷酸包括(a)一種分離的多核苷酸，其中包含與序列表中一種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一種多核苷酸；(c)一種分離的多核苷酸，該多核苷酸與序列表中列出的一種多核苷酸之間具有至少95％，96％，97％，98％，或99％的同一性；(d)序列表中列出的一種分離的多核苷酸；(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的一種多肽序列之間具有至少95％，96％，97％，98％，或99％的同一性；(f)一種分離的多核苷酸，其中包含編碼序列表中一種多肽的多核苷酸序列；(g)一種分離的多核苷酸，其具有如下多核苷酸序列所述序列編碼的多肽與序列表中一種多肽序列之間具有至少95％，96％，97％，98％，或99％的同一性；(h)一種分離的多核苷酸，該多核苷酸編碼序列表中的一種多肽；(i)一種分離的多核苷酸，該多核苷酸具有或包含與序列表所列的一種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)一種分離的多核苷酸，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的一種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)選片段包括一種分離的多核苷酸，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來自序列表中所列的一種序列的至少15、30、50或100個連續(xù)核苷酸；或者所述多核苷酸序列具有從序列表的一種序列中截短或缺失了至少30、50或100個連續(xù)核苷酸所得的序列。
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，包括其有1個或多個單核苷酸多態(tài)性(SNP)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的多肽變體的多核苷酸即所述多肽變體包含序列表中的一種氨基酸序列，并且該氨基酸序列中以任意組合取代、缺失或添加了50-30、30-20、20-10、10-5、5-3、3-2、2-1或1個氨基酸殘基。
另一方面，本發(fā)明提供了作為本發(fā)明所述DNA序列的RNA轉(zhuǎn)錄物的多核苷酸。因此，本發(fā)明提供了下述RNA多核苷酸以及與其互補(bǔ)的RNA多核苷酸(a)其包括編碼序列表中一種多肽的DNA序列的RNA轉(zhuǎn)錄物；(b)其本身為編碼序列表中一種多肽的DNA序列的RNA轉(zhuǎn)錄物；(c)其包括序列表中一種DNA序列的RNA轉(zhuǎn)錄物；或者(d)其本身是序列表中一種DNA序列的RNA轉(zhuǎn)錄物。
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序列。編碼序列表中多肽的多核苷酸序列可以與序列表中多肽的編碼序列相同，或者它也可以是序列表所列序列之外的序列，但由于遺傳密碼的豐余性(簡并性)，它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中基因家族的其它蛋白相關(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)選多肽及多核苷酸預(yù)計與它們的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)選的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，或者可以用公知的和商業(yè)化的技術(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，或者與其它編碼序列位于同一閱讀框的成熟多肽的編碼序列，所述其它序列例如編碼前導(dǎo)或分泌序列、前-、或原-、或前原-蛋白序列、或其它融合肽部分的序列。例如，可以編碼有助于融合多肽純化的標(biāo)記序列。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.)中提供的，以及見Gentz等，ProcNatl Acad Sci USA(1989)86821-824一文中的描述，或者為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，剪接及多腺苷酸化信號，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)明多肽的全長cDNA及基因組克隆，以及可以用來分離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)的其它基因(包括編碼人源平行進(jìn)化同系物(paralogs)的基因以及其它物種來源的直向同系物(orthologs)及平行進(jìn)化同系物的基因)的cDNA及基因組克隆。優(yōu)選的探針及引物通常包括至少15個核苷酸，優(yōu)選至少30個核苷酸，如果不是至少100個核苷酸，也可以為至少50個。特別優(yōu)選的探針為30-50個核苷酸。特別優(yōu)選的引物為20-25個核苷酸。
編碼本發(fā)明多肽的多核苷酸，包括來自其它物種的同系物，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，5xSSC(150mM NaCI，15mM檸檬酸三鈉)、50mM磷酸鈉(pH 7.6)，5xDenhardt′s溶液、10％葡聚糖硫酸酯、以及20μg/ml變性剪切后的鮭魚精DNA；然后在約65℃用0.1xSSC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的多核苷酸，優(yōu)選地，該多核苷酸具有至少100個核苷酸，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，很多情況下，分離的cDNA序列是不完整的，其編碼多肽的區(qū)域不會一直延伸至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”(聚合反應(yīng)過程中該酶保持與模板結(jié)合的能力的一個指標(biāo))，因而在第一鏈cDNA合成過程中不能合成mRNA模板的完整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)。近來該技術(shù)有一些改進(jìn)，以Marathon(商標(biāo)名)技術(shù)(Clontech Laboratories Inc.)為代表，例如已大大簡化了較長cDNA的篩選。在Marathon(商標(biāo)名)技術(shù)中，從選定組織提取mRNA，從中制備cDNA，并且在每個末端都連接“銜接頭(adaptor)”序列。然后，聯(lián)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)，所述嵌套引物是經(jīng)設(shè)計而在擴(kuò)增產(chǎn)物內(nèi)部退火的引物(通常，一個為與銜接頭序列的更偏3′側(cè)退火的銜接頭特異性引物，另一引物為與已知基因序列的更偏5′側(cè)退火的基因特異性引物)。然后，通過DNA測序分析該反應(yīng)產(chǎn)物，通過下述方法構(gòu)建全長cDNA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?？梢杂枚喾N常規(guī)實(shí)驗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 Molecular Biology(1986)和Sambrook等(同上)。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(scrape loading)、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和夜蛾(Spodoptera)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。
有多種表達(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、噬菌體、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，及來源于其組合的載體，例如源自質(zhì)粒及噬菌體遺傳元件的載體，例如粘粒及噬菌粒。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.，(如上)一書中描述的方法。可以將合適的分泌信號導(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)明多肽的表達(dá)是為了用于篩選實(shí)驗，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)驗前收獲細(xì)胞。如果多肽分泌入培養(yǎng)基中，那么可回收培養(yǎng)基以回收及純化所述多肽。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)明多肽可以用作診斷試劑，檢測相關(guān)基因中的突變。對突變形式的基因的檢測，其特征在于cDNA或基因組序列中列于序列表中的多核苷酸，且其與功能紊亂相關(guān)。本發(fā)明將提供一診斷工具，該診斷工具可以輔助診斷或明確診斷疾病或疾病易感性，所述疾病是由基因的低表達(dá)、過表達(dá)或表達(dá)在空間或時間上的變化引起。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。
用于診斷的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，或者用其它擴(kuò)增技術(shù)進(jìn)行酶性擴(kuò)增。RNA或cDNA也可以以類似的方式應(yīng)用。通過擴(kuò)增產(chǎn)物與正常基因型相比大小上的變化來檢測缺失和插入。通過將擴(kuò)增的DNA與標(biāo)記后的表1中基因的核苷酸序列雜交可檢測點(diǎn)突變。用RNA酶消化或解鏈溫度的差異可將錯配的雙螺旋體與完美匹配的序列區(qū)分。還可以以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)來檢測DNA序列的差異。還可以用核酸酶保護(hù)試驗或者化學(xué)切割方法檢測出特定位點(diǎn)上的序列變化，所述保護(hù)例如RNA酶及S1保護(hù)(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，并且可以用來研究分子遺傳學(xué)中的多種問題，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)明引述的其它文獻(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。表達(dá)的減少或增加可以用本領(lǐng)域熟知的任一檢測多核苷酸量的方法在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印跡法及其它雜交方法。用于測定蛋白，如本發(fā)明多肽在來自宿主的標(biāo)本中的水平的分析技術(shù)已為本領(lǐng)域技術(shù)人員所熟知。所述分析方法包括放射免疫測定、競爭結(jié)合試驗、Western印跡分析及ELISA試驗。
因此另一方面，本發(fā)明涉及一種診斷試劑盒，其包括(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)錄體；(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)中都包含一種基本組分。該試劑盒可以用來診斷疾病或?qū)膊〉囊赘行?，尤其是本發(fā)明所述疾病。
本發(fā)明所述多核苷酸序列對于染色體定位研究很有價值。序列表中的序列特異性地靶向單個人源染色體的特定位點(diǎn)并可與該位點(diǎn)雜交。在本發(fā)明的染色體上對相關(guān)序列作圖是使這些序列和基因相關(guān)疾病間建立關(guān)聯(lián)的重要的第一步。一旦將序列定位到確切的染色體位置，就可以將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 JohnsHopkins University 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)。為了用所述試驗板確定基因的染色體定位，使用根據(jù)RH DNA上的目的基因設(shè)計的引物進(jìn)行93次PCR反應(yīng)。這些DNA中的每一個都包括維持在倉鼠背景(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，它們指示目的基因的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。所述研究導(dǎo)致能確定本發(fā)明所述多核苷酸的表達(dá)模式，從而通過檢測編碼所述多肽的mRNA來指示組織中所編碼的多肽的表達(dá)模式。所用的技術(shù)為本領(lǐng)域熟知，包括對排列在載網(wǎng)上的克隆進(jìn)行原位雜交技術(shù)，例如cDNA微陣列雜交(Schena et al，Science，270，467-470，1995 and Shalon et al，Genome Res，6，639-645，1996)以及核苷酸擴(kuò)增技術(shù)如PCR。優(yōu)選的方法使用Perkin Elmer公司提供的TAQMAN(商標(biāo)名)技術(shù)。這些研究的結(jié)果可以為所述多肽在生物體內(nèi)的正常功能提供指示。此外，mRNA的正常表達(dá)模式與同一基因的替代形式(例如，多肽編碼能力有變或具有調(diào)節(jié)性突變的那些)所編碼的mRNA的表達(dá)模式間的對比研究，可以為本發(fā)明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、空間或單純量上的特性。
本發(fā)明另一方面還涉及抗體。本發(fā)明多肽或其片段，或表達(dá)它們的細(xì)胞，都可以用作免疫原，以制備針對本發(fā)明多肽具有免疫特異性的抗體?！懊庖咛禺愋浴币辉~是指所述抗體與本發(fā)明多肽間的親和力明顯大于其與現(xiàn)有技術(shù)中其它相關(guān)多肽間的親和力。
抗本發(fā)明多肽的抗體可以通過常規(guī)方法向動物，優(yōu)選非人動物，施用所述多肽或含表位的片段、或細(xì)胞而獲得。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，也可以調(diào)整后用來制備抗本發(fā)明多肽的單鏈抗體。另外，轉(zhuǎn)基因小鼠，或其它生物，包括其它哺乳動物，也可以用于表達(dá)人源化抗體。
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)明多肽的抗體也可以用來治療本發(fā)明所述疾病。
本發(fā)明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，該方法包括用足夠量的本發(fā)明多肽接種哺乳動物，使所述哺乳動物產(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渌镔|(zhì)，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)一步包括適當(dāng)?shù)妮d體。由于多肽可能在胃中被降解，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滲(instonic)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，只需在使用前臨時加入無菌液態(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)以及其它本領(lǐng)域已知系統(tǒng)。劑量取決于疫苗的比活性，可根據(jù)常規(guī)經(jīng)驗容易地確定。
本發(fā)明多肽具有與1種或多種病理狀態(tài)有關(guān)的1種或多種生物功能，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用于治療及預(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、化合物集合、以及天然產(chǎn)物混合物。如此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、與帶有所述多肽的細(xì)胞或細(xì)胞膜、或與其融合蛋白的結(jié)合。或者，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，這些篩選方法可以使用適于帶有該多肽的細(xì)胞的檢測系統(tǒng)，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。通常在有已知激動劑的情況下測定對激活作用的抑制劑，此時可觀察候選化合物存在時該激動劑的活化效果。另外，篩選方法可以簡單地包括將候選化合物與含本發(fā)明多肽的溶液混合，形成混合物，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)明多肽可以用于常規(guī)低容量篩選方法以及還可用于高流通量篩選(high-throughput screening)(HTS)方式。所述HTS方式不僅可以使用成熟的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 et al，Anal Biochem.，246，20-29，(1997)一書描述的毫微孔(nanowell)方法。
融合蛋白，例如由Fc部分和如上所述的表I中基因的多肽形成的融合蛋白，也可用于高流通量篩選試驗，來鑒定本發(fā)明多肽的拮抗劑(見D.Bennettet al.，J Mol Recognition，852-58(1995)；and K.Johanson et al.，J Biol 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設(shè)計篩選方法，來檢測所加入的化合物對細(xì)胞中mRNA及多肽的生產(chǎn)的影響。例如，可構(gòu)建ELISA試驗，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)胞結(jié)合型多肽的水平。用該方法能從適當(dāng)操作后的細(xì)胞或組織中發(fā)現(xiàn)可抑制或增加多肽的生產(chǎn)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，其中所述多肽被放射性同位素(例如，125I)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，然后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。其它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。完成所述試驗的常規(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)的寡核苷酸或蛋白，所述多肽的底物，受體，酶等，例如配體、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中的基因通過顯微注射導(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發(fā)現(xiàn)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。其它有用的轉(zhuǎn)基因動物有所謂的“敲除(knock-out)”動物，其中與本發(fā)明多肽相應(yīng)且被細(xì)胞中內(nèi)源DNA序列編碼的動物直向進(jìn)化同系物的表達(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)還提供了一種完整動物表達(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)明多肽的重組細(xì)胞；(c)表達(dá)本發(fā)明多肽的細(xì)胞膜；或者(d)抗本發(fā)明多肽的抗體；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)物或其它免疫球蛋白表達(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，那么已將其從原初的環(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、基因操作或其它任一重組方法導(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的。
“分泌型蛋白的活性或者分泌型多肽的活性”或者“分泌型蛋白的生物活性或者分泌型多肽的生物活性”是指所述分泌型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。
“分泌蛋白的基因”是指包含了所附任一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?，但不限于，單鏈及雙鏈DNA，單鏈和雙鏈區(qū)混合體的DNA，單鏈及雙鏈RNA，以及單鏈和雙鏈區(qū)混合的RNA，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與雙鏈區(qū)的混合體。此外，“多核苷酸”還指三鏈區(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個或多個已修飾的堿基的DNA或RNA以及為穩(wěn)定或其它原因?qū)羌苄揎椇蟮腄NA或RNA?！靶揎椀摹眽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?？蓪NA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)、酶促或代謝修飾形式，以及病毒及細(xì)胞特有的化學(xué)形式DNA及RNA?！岸嗪塑账帷暹€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彼此相連的氨基酸的任一多肽(即肽等排物(isostere))?！岸嚯摹奔瓤梢灾付替湺嚯模部梢灾搁L鏈多肽。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種由基因編碼的氨基酸以外的氨基酸。“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)鏈以及氨基或羧基末端。應(yīng)該理解的是相同的修飾可以以同等程度或不同程度出現(xiàn)在給定多肽的數(shù)個位點(diǎn)。另外，給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。修飾包括乙?；?、酰化、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、共價連接磷脂酰肌醇(phosphotidylinositol)、交聯(lián)、環(huán)化、形成二硫鍵、去甲基化、形成共價交聯(lián)、生成胱氨酸、生成焦谷氨酸、甲?；?、γ-羧基化、糖基化、GPI錨定形成、羥基化、碘化、甲基化、豆蔻?；?、氧化、蛋白裂解性加工、磷酸化、異戊二烯化、外消旋化、硒代化(selenoylation)、磺化、借助轉(zhuǎn)運(yùn)-RNA向蛋白添加氨基酸如精氨酸化，以及遍在化(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 Protein ModificationsPerspectives and Prospects，1-12，in Post-translational Covalent Modification ofProteins，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 SynthesisPosttranslationalModifications and Aging″，Ann NY Acad Sci，663，48-62，1992)。
多肽序列的“片段″是指比參考序列短但是基本保留了與參考多肽相同的生物功能或活性的多肽序列。多核苷酸序列的“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，但是保留了參考多核苷酸或參考多肽的基本特性。多核苷酸的常見變體在核苷酸序列上不同于參考多核苷酸。該變體的核苷酸序列的改變可能改變或不改變由所述參考多核苷酸編碼的多肽的氨基酸序列。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，改變是有限的，從而使參考多肽的序列與該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1個或多個取代、插入、缺失的任意組合而在氨基酸序列上不同。取代或插入的氨基酸殘基可以由或不由遺傳密碼子編碼。常見的保守取代包括Gly，Ala；Ala，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，或者也可以是不知道能天然生成的變體。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一個基因的2個或多個備選形式中的一種。
“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)基因組的單個核苷酸位置上出現(xiàn)核苷酸變化。SNP可發(fā)生于基因組的一個基因內(nèi)或多個基因間區(qū)域中。SNP可以用等位基因特異性擴(kuò)增(ASA)來分析。這項操作需要至少3個引物。其中用到一種共同引物，它與待分析的多態(tài)性反向互補(bǔ)。該共同引物從多態(tài)性堿基起為50-1500bp。另外兩個(或多個)引物是彼此基本相同的，但最后的3’堿基有所變動，以便與構(gòu)成多態(tài)性的2個(或多個)等位基因之一匹配。然后在標(biāo)本DNA上進(jìn)行兩個(或多個)PCR反應(yīng)，每個PCR反應(yīng)都使用上述共同引物和其中一種等位特異性引物。
本發(fā)明中的“剪接變體”是指來自相同的基因組DNA序列，但經(jīng)歷了不同的RNA剪接的的RNA分子。不同的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，它們導(dǎo)致制備出不只一種mRNA分子，其中的每一種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對應(yīng)性，或兩多核苷酸序列之間核苷酸與核苷酸的對應(yīng)性。
“％同一性”-對于不完全對應(yīng)的序列，可以測定“％同一性”。通常將兩種要進(jìn)行比較的序列對應(yīng)排列，以便得到序列間的最大相關(guān)程度。這包括為提高對應(yīng)排列程度，在其中的1或兩個序列中插入“間隙”?？梢跃兔恳粎⑴c比較的序列的全長來測定％同一性(稱為整體對應(yīng)排列)，這特別適用于長度相等或非常近似的序列，或者也可以就指定長度的較短序列進(jìn)行測定(稱為局部對應(yīng)排列)，這更適用于長度不等的多個序列。
“相似性”是對兩種多肽序列間相關(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，不僅涉及殘基對之間的確切對應(yīng)(如同一性的計算)，也涉及并非確切對應(yīng)的殘基對，其中所述確切對應(yīng)的殘基對是指，其中每一殘基來自參與對比的不同序列，所述并非確切對應(yīng)的殘基對是指，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”，可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，版本9.1(Devereux J et al，NucleicAcids Res，12，387-395，1984，可得自Genetics Computer Group，Madison，Wisconsin，USA)中的程序，例如程序BESTFIT和GAP，可用來測定兩種多核苷酸序列間的％同一性以及兩種多肽序列間的％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種多核苷酸或兩種多肽序列，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將兩序列對應(yīng)排列，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，期望對全長序列進(jìn)行對應(yīng)排列。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應(yīng)排列時測定％同一性和相似性。
用于測定序列間同一性和/或相似性的其它程序也為本領(lǐng)域所已知，例如BLAST程序家族(Altschul S F等，J Mol Biol，215，403-410，1990，AltschulS F等，Nucleic Acids Res.，25389-3402，1997，可得自National Center forBiotechnology Information(NCBI)，Bethesda，Maryland，USA，也可以從NCBI在www.ncbi.nlm.nih.Gov的主頁獲得)和FASTA(Pearson W R，Methods inEnzymology，183，63-99，1990；Pearson W R and Lipman D J，Proc Nat AcadSci USA，85，2444-2448，1988，是Wisconsin Sequence Analysis軟件包的一部分)。
優(yōu)選地，使用BLOSUM62氨基酸取代矩陣(Henikoff S and Henikoff J 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程序測定待測多核苷酸或多肽序列與作為參考的多核苷酸或多肽序列之間的％同一性，其中將所述待測序列與所述參考序列最進(jìn)行最佳對應(yīng)排列，并將程序的參數(shù)設(shè)為如上所述的缺省值。
“同一性指數(shù)”是序列相關(guān)程度的度量，其可用來比較候選序列(多核苷酸或多肽)和參考序列。因此，例如，與參考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)為與參考序列是相同的，只是相對于參考序列的每100個核苷酸，在候選多核苷酸序列上有平均最多達(dá)5處差異。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)在參考多核苷酸序列5′或3′末端或者兩末端之間的任一位置，可以單個地散布在參考序列的核苷酸之間，或者也可以以1個或多個連續(xù)集團(tuán)的方式散布在參考序列內(nèi)。換句話說，為了得到與參考多核苷酸序列間同一性指數(shù)為0.95的多核苷酸序列，可以使參考序列的每100個核苷酸中有平均最多達(dá)5個缺失、取代或插入，或其任一組合，如上文所述。必要時對其它同一性指數(shù)，例如0.96，0.97，0.98和0.99的情況也可以照此辦理。
類似地，就多肽而言，與參考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)為與參考序列是相同的，只是相對于參考序列的每100個氨基酸，在候選多肽序列上有平均最多達(dá)5處差異。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)在參考多肽序列的氨基末端或羧基末端或者兩末端之間的任一位置，可以單個地散布在參考序列的氨基酸之間，或者也可以以1個或多個連續(xù)集團(tuán)的方式散布在參考序列內(nèi)。換句話說，為了得到與參考序列間同一性指數(shù)為0.95的多肽序列，可以使參考序列的每100個氨基酸中有平均最多達(dá)5個缺失、取代或插入，或其任一組合，如上文所述。必要時對其它同一性指數(shù)，例如0.96，0.97，0.98和0.99的情況也可以照此辦理。
核苷酸或氨基酸差異數(shù)與同一性指數(shù)之間的關(guān)系可以表述為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，且其中當(dāng)xa和I的乘積為非整數(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)域的一個廣義詞匯，意指與參考序列間有很高的序列相關(guān)程度的多核苷酸或多肽序列。所述的相關(guān)程度可通過如上述測定兩種序列之間的同一性和/或相似性的程度來定量。屬于這一廣義詞匯范疇內(nèi)的有“直向進(jìn)化同系物″及“平行進(jìn)化同系物″?！爸毕蜻M(jìn)化同系物″是指與另一物種中的多核苷酸或多肽功能等價的多核苷酸或多肽?！捌叫羞M(jìn)化同系物″是指同一物種中功能類似的多核苷酸或多肽。
“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)。在一個舉例中，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)。
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表IV.用SybrMan檢測mRNA的組織特異性的定量表達(dá)用SYBR-Green定量PCR(Applied Biosystems，F(xiàn)oster City，CA；參見Schmittgen T.D.et al.，Analytical Biochemistry 285194-204，2000)以及從各種人組織中制備的人cDNA測定所述基因的mRNA的組織特異性定量表達(dá)模式。使用序列表中每個基因的第一種核酸序列設(shè)計基因特異性PCR引物。域循環(huán)(Ct)定義為部分循環(huán)數(shù)，在該循環(huán)數(shù)的情況下通過剪切探針生成的報告分子熒光達(dá)到10倍于背景的域值。在序列檢測系統(tǒng)軟件預(yù)測到一個以上的PCR產(chǎn)物的情況下，可用Taqman進(jìn)行特定的PCR擴(kuò)增(如在特定基因情況下所提示的那樣)。
在每種基因的第一個表中，顯示了對各種人組織中身份鑒別基因(geneof identification(GOI))mRNA的兩次平行檢測的結(jié)果(第3列和第4列)。表中顯示了每種組織RNA的兩次平行檢測的平均GOI mRNA拷貝數(shù)(第5列)。檢測了來自每種組織RNA的18S rRNA的平均值(第6列)并用以標(biāo)準(zhǔn)化。為使每種組織具有相同的18S rRNA量(50ng)，用50ng除以所測每種組織的18SrRNA的量(第6列)，計算出標(biāo)準(zhǔn)化系數(shù)(第7列)。每個GOI標(biāo)準(zhǔn)化系數(shù)乘以平均mRNA拷貝數(shù)即可得到每50ng總RNA中mRNA的拷貝數(shù)(第8列)。
倍數(shù)變化顯示在每種基因的第二個表中，其僅對有對照物的疾病組織進(jìn)行了計算。沒有對照物的所有標(biāo)本在倍數(shù)變化列中顯示空白。另外，倍數(shù)變化的數(shù)值是疾病標(biāo)本和正常標(biāo)本相比較的倍數(shù)變化。所以，任何正常標(biāo)本的后面沒有倍數(shù)變化數(shù)值。對于有成對腫瘤的患者(結(jié)腸，肺和乳腺)，每種腫瘤與其特定的正常對照物相比較。如果不存在與患者相匹配的正常/疾病對，那么每種疾病標(biāo)本要與同一組織類型的所有正常標(biāo)本的平均值相比較。例如，不能應(yīng)用來自提供阿爾茨海默(Alzheimer)腦的同一患者中的正常腦。在進(jìn)行倍數(shù)變化的檢測中，應(yīng)用3個正常腦標(biāo)本和4個阿爾茨海默腦標(biāo)本。取3個正常標(biāo)本的平均值，再將每個阿爾茨海默標(biāo)本與該平均值進(jìn)行比較。
縮寫ALZ阿爾茨海默氏病CTCLONTECH(1020 East Meadow Circle Palo Alto，CA 94303-4230，USA)KC由GSK研究者制備的標(biāo)本COPD慢性阻塞性肺病
Endo內(nèi)皮細(xì)胞的VEGF血管內(nèi)皮細(xì)胞生長因子bFGF堿性成纖維細(xì)胞生長因子BM骨髓Osteo成骨細(xì)胞OA骨關(guān)節(jié)炎RA類風(fēng)濕性關(guān)節(jié)炎PBL外周血淋巴細(xì)胞PBMNC外周血單核細(xì)胞HIV人類免疫缺陷病毒HSV單純皰疹病毒HPV人乳頭瘤病毒基因名稱sbg960509cbrecpt在正常和疾病標(biāo)本中總體表達(dá)最低。在全腦，胚胎肝臟和子宮中有最高的正常表達(dá)。在2份肺腫瘤標(biāo)本，一份乳腺腫瘤標(biāo)本和一份正常乳腺標(biāo)本中有最高的疾病表達(dá)。在4份結(jié)腸腫瘤的一份中下調(diào)提示其與結(jié)腸癌有關(guān)。在4份AD腦標(biāo)本的2份中下調(diào)和在全腦中的高表達(dá)，提示其參與阿爾茨海默氏病。在3份COPD肺標(biāo)本中都下調(diào)，和在4份哮喘肺標(biāo)本中都下調(diào)，提示在COPD和哮喘中存在該基因。在3份心臟標(biāo)本的2份中上調(diào)，提示其在非阻塞性和阻塞性DCM中的作用。由于Cts＞35，上述模式很難解釋。免疫細(xì)胞中有中度到低度的表達(dá)。在OA和RA滑膜中有中度表達(dá)。
基因名稱sbg960509cbrecpt
基因名稱sbg614126complfH在正常和疾病標(biāo)本中，有中度到低度的總體表達(dá)。在肝臟和胚胎肝臟中有最高的正常表達(dá)。在全腦，卵巢和子宮中可見較低(但仍然是明顯的)表達(dá)。在2份乳腺腫瘤樣品，一份正常腦標(biāo)本，一份正常肺標(biāo)本，多份OA滑膜標(biāo)本的一份中以及在HSV感染的MRC5細(xì)胞中有最高的疾病表達(dá)。在4份結(jié)腸腫瘤的一份中上調(diào)提示其在結(jié)腸腫瘤中的作用。在4份肺腫瘤的2份中下調(diào)，在4份乳腺腫瘤的1份中上調(diào)提示其在肺和乳腺癌中的作用。在全部3份COPD肺標(biāo)本中下調(diào)和全部4份哮喘肺中下調(diào)提示其參與慢性阻塞性肺疾病和哮喘。在3份心臟標(biāo)本的一份中上調(diào)提示其在DCM中的作用。在HSV中上調(diào)提示其作為潛在的宿主因子與單純皰疹病毒有關(guān)。在免疫細(xì)胞，RA和OA滑膜骨和軟骨有中度到低度的表達(dá)。
基因名稱sbg614126complfH
基因名稱sbg120703RNase在正常和疾病標(biāo)本中有中度到低度的總體表達(dá)。在全腦和唾液腺中有最高水平的正常表達(dá)。在胚胎肝臟和胸腺中有中度表達(dá)。在2份正常的肺標(biāo)本，一份肺腫瘤標(biāo)本，正常軟骨庫和HSV感染的MRC5細(xì)胞中有最高的疾病表達(dá)。在4份結(jié)腸腫瘤的一份中上調(diào)提示其在結(jié)腸癌中的作用。在4份肺腫瘤標(biāo)本的2份中下調(diào)提示其可能與肺癌有關(guān)。在4份乳腺腫瘤的2份中上調(diào)提示其參與乳腺癌。在所有3份COPD肺標(biāo)本中都下調(diào)提示其參與COPD。在所有3份心臟標(biāo)本中都上調(diào)提示在心臟疾病，如DCM和缺血中有該基因。在OA和RA的滑膜和OA的骨標(biāo)本中高表達(dá)提示其可能參與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎。在HSV中上調(diào)提示該基因作為潛在的宿主因子與單純皰疹病毒有關(guān)。在免疫細(xì)胞中有中度到低度的表達(dá)。

基因名稱sbg120703RNase
基因名稱sbg98530TS
在正常和疾病標(biāo)本中有中度的總體表達(dá)。在全腦，子宮內(nèi)膜和睪丸中有最高的正常表達(dá)。在正常心臟，骨骼肌和食管中有中度表達(dá)。在大部分胃腸道標(biāo)本和女性生殖道標(biāo)本中顯示表達(dá)。在一份結(jié)腸腫瘤標(biāo)本，所有3份心臟標(biāo)本，和軟骨細(xì)胞中有最高的疾病表達(dá)。數(shù)據(jù)突出顯示肌肉特異性表達(dá)模時。在4份結(jié)腸腫瘤的一份中上調(diào)，在4份乳腺腫瘤的2份中上調(diào)提示其參與結(jié)腸腫癌和乳腺癌。在所有3份COPD標(biāo)本中下調(diào)提示其在慢性阻塞性肺病中的作用。在HSV中下調(diào)提示其作為潛在的宿主因子與單純皰疹病毒有關(guān)。在免疫細(xì)胞中有中度到低度的總體表達(dá)。在軟骨細(xì)胞和OA和RA的滑膜中高表達(dá)提示其可能參與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎。

基因名稱sbg98530TS
基因名稱sbg563917RDP在正常和疾病標(biāo)本中有中度到低度的總體表達(dá)。在睪丸，肝臟，氣管和全腦中有最高的正常表達(dá)。在大多數(shù)胃腸道標(biāo)本中顯示良好表達(dá)。在T細(xì)胞，B細(xì)胞，中性粒細(xì)胞和嗜酸性粒細(xì)胞中有最高的疾病表達(dá)。在4份乳腺腫瘤的1份中上調(diào)提示其參與乳腺癌。在所有3份COPD肺中下調(diào)提示其參與慢性阻塞性肺病。在在缺血性心臟標(biāo)本中下調(diào)提示在缺血性心臟疾病中涉及該基因。在VEGF和bFGF治療的內(nèi)皮細(xì)胞中下調(diào)提示其在血管生成的作用。在HSV中上調(diào)提示其作為潛在的宿主因子與單純皰疹病毒有關(guān)。

基因名稱sbg563917RDP
基因名稱sbg618069LRR在正常和疾病標(biāo)本中有低的總體表達(dá)。在全腦，胎腦，小腦和胸腺中有最高的正常表達(dá)。在1份結(jié)腸腫瘤標(biāo)本，1份肺腫瘤標(biāo)本，和未感染的PBL細(xì)胞中有最高的疾病表達(dá)。在4份結(jié)腸腫瘤的2份中下調(diào)提示其在結(jié)腸癌中的作用。在4份肺腫瘤的一份中上調(diào)和4份乳腺腫瘤的2份中上調(diào)提示其在肺癌和乳腺癌中的作用。在所有3份COPD肺標(biāo)本中下調(diào)提示該基因在COPD中的作用。其在受到刺激的骨髓中上調(diào)。在HIV感染的細(xì)胞系中下調(diào)，和在免疫細(xì)胞中的中度表達(dá)提示其與HIV有關(guān)。在HSV中上調(diào)提示其作為潛在的宿主因子與單純皰疹病毒有關(guān)。

基因名稱sbg618069LRR
基因名稱sbg934114Relaxin在正常和疾病標(biāo)本中有低的總體表達(dá)。在睪丸，肝臟和全腦中有最高的正常表達(dá)。在3份正常肺標(biāo)本，一份正常腫瘤標(biāo)本中，HSV感染的MRC5細(xì)胞中，腺樣增殖體(adenoid)中和T細(xì)胞中有最高的疾病表達(dá)。在2份正常肺標(biāo)本中，1份肺腫瘤標(biāo)本中，1份正常乳腺標(biāo)本中，1份乳腺腫瘤標(biāo)本中和未感染的PBL標(biāo)本中有最高的疾病表達(dá)。在4份結(jié)腸腫瘤的1份中下調(diào)，在4份肺腫瘤的2份中下調(diào)提示其在結(jié)腸癌和肺癌中的作用。在所有3份COPD肺標(biāo)本中下調(diào)，和4份哮喘肺標(biāo)本的3份中上調(diào)提示COPD和哮喘涉及該基因。在3份心臟標(biāo)本的2份中上調(diào)提示其在肺阻塞性和阻塞性DCM中的作用。在OA軟骨庫中下調(diào)，在RA和OA滑膜，OA骨，和軟骨細(xì)胞中低表達(dá)提示其參與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎。在HIV感染的原代細(xì)胞系中下調(diào)提示其與HIV有關(guān)。在HSV中上調(diào)提示其作為潛在的宿主因子與單純皰疹病毒有關(guān)。
基因名稱sbg934114Relaxin
基因名稱sbg99174LOX-like在正常和疾病標(biāo)本中中度的總體表達(dá)。在全腦，肝臟，皮膚，脾臟，睪丸有最高的正常表達(dá)。在女性生殖道標(biāo)本中和胃腸道標(biāo)本中有相對好的表達(dá)。在一份正常肺標(biāo)本中，一份哮喘肺標(biāo)本中，中性粒細(xì)胞，嗜酸性粒細(xì)胞，2份RA滑膜標(biāo)本中和一份OA骨標(biāo)本中有最高的疾病表達(dá)。在4份肺腫瘤標(biāo)本的1份中下調(diào)提示其可能參與肺癌。在4份乳腺腫瘤的2份中上調(diào)提示其參與乳腺癌。在4份AD腦的1份中下調(diào)和在腦中觀察到的高表達(dá)提示其參與阿爾茨海默氏病。在3份COPD肺標(biāo)本的2份中下調(diào)提示其參與慢性阻塞性肺病。在4份哮喘肺標(biāo)本的1份中上調(diào)提示其在哮喘中的作用。在OA的軟骨中下調(diào)和在OA和RA的滑膜中高表達(dá)提示其可能參與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎。在T細(xì)胞中證實(shí)高表達(dá)為其在RA/OA中的作用提供了補(bǔ)充的證據(jù)。在其它免疫細(xì)胞中為中度表達(dá)。
基因名稱sbg99174LOX-like
基因名稱sbg995002PIGR(Taqman)在正常和疾病標(biāo)本中有極低的總體表達(dá)。在結(jié)腸和腮腺中有最高的正常表達(dá)。在一份肺腫瘤標(biāo)本中和一份結(jié)腸腫瘤標(biāo)本中有最高的疾病表達(dá)。在4份結(jié)腸腫瘤的1份中和4份肺腫瘤的1份中上調(diào)提示其在結(jié)腸癌和肺癌中的作用。在4份AD腦標(biāo)本的3份中下調(diào)和在全腦中高表達(dá)提示其參與阿爾茨海默氏病。在所有3份COPD肺標(biāo)本中下調(diào)提示該基因與COPD有關(guān)。在缺血性和非阻塞性DCM心臟標(biāo)本中下調(diào)提示該基因在心血管疾病中的作用。其在受到刺激的骨髓標(biāo)本中上調(diào)。在HSV中上調(diào)提示其作為潛在的宿主因子與單純皰疹病毒有關(guān)。其在中性粒細(xì)胞和嗜酸性粒細(xì)胞中高表達(dá)。

基因名稱sbg995002PIGR
基因名稱sbg1033026C1q在正常和疾病標(biāo)本中有低度到中度的總體表達(dá)。在皮下脂肪組織，皮下脂肪，全腦和心臟中有最高的正常表達(dá)。在3份心臟標(biāo)本中有最高的疾病表達(dá)。在4份肺腫瘤標(biāo)本的1份中下調(diào)和在4份乳腺腫瘤標(biāo)本的2份中上調(diào)提示該基因在肺癌和乳腺癌中的作用。在4份AD腦標(biāo)本的2份中上調(diào)提示其參與阿爾茨海默氏病。在所有3份心臟標(biāo)本中上調(diào)提示參與心血管疾病，例如非阻塞性和阻塞性DCM和缺血。其在所有免疫細(xì)胞中低表達(dá)。在OA的滑膜和骨標(biāo)本中和在RA的滑膜標(biāo)本中為低度到中度表達(dá)。

基因名稱sbg1033026C1q
基因名稱sbg1003675Rnase失敗基因名稱sbg1015258PLM在正常和疾病標(biāo)本中有低的總體表達(dá)。在子宮內(nèi)膜，下丘腦，肝臟小腸和睪丸中有最高的正常表達(dá)。在一份乳腺正常/腫瘤對中，一份正常的腦標(biāo)本中，二份阿爾茨海默氏病腦標(biāo)本中，B細(xì)胞和HSV感染的MRC5細(xì)胞中有最高的疾病表達(dá)。在4份肺腫瘤標(biāo)本的1份中下調(diào)，足以認(rèn)定其在肺癌中的作用。在4份乳腺腫瘤標(biāo)本的2份中上調(diào)提示其參與乳腺癌。在3份COPD標(biāo)本的2份中下調(diào)和在4份哮喘肺標(biāo)本的2份中下調(diào)提示其在慢性阻塞性肺病和哮喘中的作用。在阻塞性DCM心臟標(biāo)本中上調(diào)提示其在心血管疾病中有潛在的作用。在受到刺激的骨髓標(biāo)本中下調(diào)。在OA的軟骨庫中下調(diào)提示在骨關(guān)節(jié)炎中涉及該基因。在HSV感染的MRC5細(xì)胞中上調(diào)提示該基因可能是HSV中的宿主因子。在所有免疫細(xì)胞(除B細(xì)胞外)中低表達(dá)，在B細(xì)胞中中度表達(dá)。

基因名稱sbg1015258PLM
基因名稱sbg1003328IG(Taqman)中度的總體表達(dá)。在全腦，胎腦和小腦中有最高的正常表達(dá)，在結(jié)腸和乳腺中其表達(dá)水平略低。在結(jié)腸和肺腫瘤對，以及在正常和阿爾茨海默氏病腦中有最高的疾病表達(dá)。在4份乳腺腫瘤標(biāo)本的2份中明顯上調(diào)，在4份乳腺腫瘤標(biāo)本的1份中輕微上調(diào)提示在乳腺癌中涉及該基因。
在所有3份COPD標(biāo)本中下調(diào)可能提示與慢性阻塞性肺病有關(guān)。在4份哮喘標(biāo)本的1份中下調(diào)提示其在哮喘中該基因的潛在作用。在HSV感染的MRC5細(xì)胞中下調(diào)提示該基因可能在HSV中起作用。在所有3份OA的滑膜標(biāo)本中，所有3份RA滑膜標(biāo)本中，所有2份OA骨標(biāo)本中高表達(dá)，以及在T細(xì)胞和B細(xì)胞中確定的高表達(dá)提示在骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎中涉及該基因。
基因名稱sbg99174LOX-like
基因名稱sbg1003328IG
基因名稱sbg1020829SGLT在正常和疾病標(biāo)本中有低的總體表達(dá)。在全腦，腎臟和胸腺中有最高的正常表達(dá)。在腺樣增殖體，扁桃體，T細(xì)胞，B細(xì)胞和嗜酸性粒細(xì)胞中有最高的疾病表達(dá)。其有極高的免疫細(xì)胞特異性。在4份肺腫瘤標(biāo)本的1份中下調(diào)和4份乳腺腫瘤標(biāo)本的1份中上調(diào)提示其參與肺和乳腺腫瘤。在4份AD腦標(biāo)本的3份中上調(diào)提示其參與阿爾茨海默氏病。在所有3份COPD標(biāo)本中下調(diào)提示其在慢性阻塞性肺病中的作用。在受到刺激的骨髓中下調(diào)。在HSV感染的MRC5細(xì)胞中上調(diào)提示該基因可能是HSV中的宿主因子。在OA和RA標(biāo)本中中度到高度的表達(dá)提示其在骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎中的潛在作用。
基因名稱sbg1020829SGLT
基因名稱sbg1005450UDPGT其有低度到中度的總體表達(dá)。在子宮內(nèi)膜，食管和脾臟有最高的正常表達(dá)，在小腦，下丘腦，直腸和子宮有較低的表達(dá)水平。在一份OA滑膜標(biāo)本中有最高的疾病表達(dá)。在4份結(jié)腸腫瘤標(biāo)本的1份中下調(diào)可足以作出有關(guān)結(jié)腸癌的疾病斷言。在4份肺腫瘤標(biāo)本的1份中上調(diào)提示該基因在肺癌中潛在的作用。在4份AD腦標(biāo)本的2份中下調(diào)提示其參與阿爾茨海默氏病。在所有3份COPD肺標(biāo)本中和所有4份哮喘肺標(biāo)本中下調(diào)提示其參與慢性阻塞性肺病和哮喘。在HSV感染的MRC5細(xì)胞中上調(diào)提示該基因可能是HSV中的宿主因子。該基因在B細(xì)胞和樹突細(xì)胞中中度表達(dá)。
基因名稱sbg1005450UDPGT
基因名稱sbg1002620Tia有中度總體表達(dá)。在全腦，子宮內(nèi)膜，子宮肌層，胎盤和直腸中有最高的正常表達(dá)。在一份結(jié)腸正常/腫瘤對中，正常肺標(biāo)本中，一份哮喘肺標(biāo)本中，中性粒細(xì)胞，嗜酸性粒細(xì)胞，一份RA滑膜標(biāo)本中有最高的疾病表達(dá)。在代表胃腸道的所有標(biāo)本中的高水平表達(dá)提示該基因在IBS，IBD和Crohn’s病中的潛在作用。在3份COPD肺標(biāo)本的1份中下調(diào)提示其參與慢性阻塞性肺病。在4份哮喘肺標(biāo)本的1份中上調(diào)提示其在哮喘中的作用。在OA的滑膜和骨標(biāo)本中和在RA滑膜標(biāo)本中高表達(dá)。在軟骨細(xì)胞中也高表達(dá)。在免疫細(xì)胞中有不同水平的表達(dá)，其中在中性粒細(xì)胞和嗜酸性粒細(xì)胞中有最高的表達(dá)，在樹突細(xì)胞中有最低的表達(dá)。在B細(xì)胞和T細(xì)胞中以及OA的標(biāo)本中確定的高表達(dá)表明，該基因與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎有關(guān)。
基因名稱sbg1002620TIa
基因名稱sbg1002620TIb中度到高度的總體表達(dá)。在全腦，子宮內(nèi)膜，空腸，胎盤，胸腺和膀胱有最高的正常表達(dá)。在一份結(jié)腸正常/腫瘤對中，一份正常的肺標(biāo)本中，一份哮喘肺標(biāo)本中，中性粒細(xì)胞中和嗜酸性粒細(xì)胞中有最高的疾病表達(dá)。在所有胃腸道標(biāo)本中的強(qiáng)表達(dá)提示該基因與IBS，IBD和Crohn’s病有關(guān)。在4份肺腫瘤標(biāo)本的1份中下調(diào)可足以作出有關(guān)肺癌的疾病斷言。在所有3份COPD肺標(biāo)本中下調(diào)提示其參與慢性阻塞性肺病。在4份哮喘肺標(biāo)本的1份中上調(diào)提示其在哮喘中的作用。在3份心臟標(biāo)本的2份中上調(diào)該基因可能在非阻塞性和阻塞性擴(kuò)張型心肌病中起作用。在RA和OA的滑膜標(biāo)本中高表達(dá)，以及在軟骨細(xì)胞和T細(xì)胞中高表達(dá)提示與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎有關(guān)。

基因名稱sbg1002620TIb
基因名稱sbg102200MCTa中度到低度的總體表達(dá)。在皮下脂肪組織，全腦，胎腦，小腦和胚胎肝臟中有最高的正常表達(dá)。在4份肺腫瘤標(biāo)本的2份中，一份正傳肺標(biāo)本，一份正常乳腺標(biāo)本，和CT肺標(biāo)本中有最高的疾病表達(dá)。在4份乳腺癌標(biāo)本的1份中下調(diào)提示該基因與乳腺癌有關(guān)。在所有3份COPD肺標(biāo)本中下調(diào)提示該基因參與慢性阻塞性肺病。在OA和RA滑膜中，以及在PBL，腺樣增殖體，扁桃體，T細(xì)胞，B細(xì)胞和軟骨細(xì)胞中中度表達(dá)提示其參與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎。

基因名稱sbg102200MCTa
基因名稱sbg102200MCTb高度到中度的總體表達(dá)。在全腦，肝臟，胚胎肝臟和胸腺有最高的正常表達(dá)。在一份結(jié)腸正常/腫瘤對，一份肺正常正常/腫瘤對，一份哮喘肺標(biāo)本，樹突細(xì)胞，未感染HIV和感染的HIV的PBL細(xì)胞中有最高的疾病表達(dá)。在4份乳腺腫瘤標(biāo)本的2份中上調(diào)可足以作出有關(guān)乳腺癌的疾病斷言。在4份AD腦標(biāo)本的1份中上調(diào)提示其在阿爾茨海默氏病中潛在的作用。在所有3份COPD肺標(biāo)本中下調(diào)提示其參與慢性阻塞性肺病。在4份哮喘肺標(biāo)本的1份中上調(diào)提示該基因在肺癌中潛在的作用。在所有免疫細(xì)胞中高表達(dá)。在OA和RA滑膜標(biāo)本中，OA骨標(biāo)本中，和軟骨細(xì)胞中也有高度到中度的表達(dá)，這提示其參與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎。

基因名稱sbg102200MCTb
基因名稱sbg1020380LYG失敗基因名稱sbg1007026SGLT良好到中度的總體表達(dá)。在全腦，小腦，下丘腦，空腸，胚胎肝臟，直腸和子宮中可見最高的正常表達(dá)。該基因在代表中樞神經(jīng)系統(tǒng)，女性生殖器官和胃腸道的標(biāo)本中顯示系統(tǒng)特異性表達(dá)。在疾病標(biāo)本中觀察到的表達(dá)證實(shí)了在正常標(biāo)本中觀察到的表達(dá)，其中在正常和阿爾茨海默氏病腦標(biāo)本中觀察到最高水平的表達(dá)。在4份結(jié)腸腫瘤標(biāo)本的1份中上調(diào)和在4份乳腺腫瘤標(biāo)本的2份中上調(diào)，以及在4份肺腫瘤的一份中下調(diào)提示該基因在結(jié)腸癌和乳腺癌中有潛在作用。在4份阿爾茨海默氏病標(biāo)本的2份中下調(diào)提示其參與阿爾茨海默氏病。在所有3份COPD標(biāo)本中下調(diào)和在4份哮喘肺標(biāo)本的2份中上調(diào)提示該基因在慢性阻塞性肺病中的潛在作用。在VEGF治療的內(nèi)皮細(xì)胞系中上調(diào)提示該基因在血管生成中可能的作用。在受到刺激的骨髓標(biāo)本中下調(diào)。在RA和OA的滑膜標(biāo)本中，OA的骨標(biāo)本中，和軟骨細(xì)胞中的高表達(dá)，以及在T細(xì)胞，B細(xì)胞，中性粒細(xì)胞和嗜酸性粒細(xì)胞中確定的高表達(dá)提示，該基因與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎有關(guān)。
基因名稱sbg1007026SGLT
基因名稱sbg1012732GLUT高度到中度的總體表達(dá)。該基因在所有參與分析的正常標(biāo)本中的表達(dá)是相對普遍的，其中在全腦，胎腦，小腦，腎臟，胚胎肝臟和胎盤中表達(dá)水平最高。該基因在疾病標(biāo)本中也有相當(dāng)普遍的表達(dá)。在所有3份COPD標(biāo)本中下調(diào)提示該基因在慢性阻塞性肺病中潛在的作用。在所有3份疾病心臟的標(biāo)本中上調(diào)提示其參與心血管疾病，如非阻塞性和阻塞性DCM和缺血。在HSV感染的MRC5細(xì)胞中下調(diào)提示該基因在HSV中可能起作用。在分化的成骨細(xì)胞中上調(diào)。在RA和OA的滑膜標(biāo)本中，在OA的骨標(biāo)本中和軟骨細(xì)胞中的高表達(dá)，和在T細(xì)胞，B細(xì)胞，樹突細(xì)胞，中性粒細(xì)胞和嗜酸性粒細(xì)胞中確定的高表達(dá)提示，該基因與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎有關(guān)。
基因名稱sbg1012732GLUT
基因名稱sbg1012732GLUTb與sbg1012732GLUT相同。
基因名稱sbg1018172CSP中度到低度的總體表達(dá)。在全腦，腎臟，甲狀腺和子宮可見最高的正常表達(dá)。該基因在代表女性生殖系統(tǒng)的所有標(biāo)本中表達(dá)。在許多正常/腫瘤肺標(biāo)本中和哮喘肺標(biāo)本中可見最高的疾病表達(dá)。在4份肺腫瘤標(biāo)本的2份中下調(diào)，4份乳腺腫瘤標(biāo)本的2份中上調(diào)提示其參與肺癌和乳腺癌。在所有3份COPD標(biāo)本中下調(diào)提示該基因在慢性阻塞性肺病中潛在的作用。在4份哮喘肺標(biāo)本的2份中上調(diào)提示其參與哮喘。在3份疾病心臟標(biāo)本的1份中上調(diào)提示其參與心血管疾病，如阻塞性DCM。在OA的軟骨庫中下調(diào)和在免疫細(xì)胞(特別是T細(xì)胞和B細(xì)胞)中確定的低表達(dá)提示，該基因與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎有關(guān)。在HSV感染的MRC5細(xì)胞中的上調(diào)提示該基因可能是HSV中的宿主因子。

基因名稱sbg1018172CSP
基因名稱sbg1004570ERGIC中度到低度的總體表達(dá)。該基因在所有參與分析的正常標(biāo)本中表達(dá)相當(dāng)普遍，其中在全腦，下丘腦，胰腺和胰頭有最高水平的表達(dá)。該表達(dá)模式提示該基因可能參與糖尿病和其它代謝性疾病。在結(jié)腸，乳腺和肺的正常/腫瘤對以及阿爾茨海默氏病腦標(biāo)本，T細(xì)胞，B細(xì)胞，樹突細(xì)胞和嗜酸性粒細(xì)胞中可見最高的疾病表達(dá)。在4份乳腺腫瘤標(biāo)本的2份中上調(diào)提示該基因在乳腺癌中的作用。在4份阿爾茨海默氏病腦標(biāo)本的2份中上調(diào)提示其參與阿爾茨海默氏病。在所有3份COPD標(biāo)本中和所有4份哮喘肺標(biāo)本中下調(diào)提示該基因在慢性阻塞性肺病和哮喘中潛在的作用。在受到刺激的骨髓中上調(diào)。
基因名稱sbg1004570ERGIC
基因名稱sbg1016995IGBrecpt中度到低度的總體表達(dá)。在全腦，肺中可見最高的正常表達(dá)，在子宮內(nèi)膜，回腸，直腸和皮膚有略低水平的表達(dá)。在皮膚中的高水平表達(dá)可能提示該基因在牛皮癬和狼瘡中可能的作用。在疾病板上的標(biāo)本中的表達(dá)模式提示該基因?qū)ο贅釉鲋丑w和扁桃體的極高特異性。在4份肺腫瘤標(biāo)本的2份中下調(diào)和在4份乳腺腫瘤標(biāo)本的2份中上調(diào)提示其參與肺癌和乳腺癌。在所有3份COPD標(biāo)本中下調(diào)提示該基因在慢性阻塞性肺病中的潛在作用。在受到刺激的骨髓中上調(diào)。在分化的成骨細(xì)胞中下調(diào)。在HIV感染的PBL細(xì)胞中上調(diào)提示該基因可能是HIV中的宿主因子。
基因名稱sbg1016995IGBrecpt
基因名稱sbg1151bSREC在正常和疾病標(biāo)本中有最高的總體表達(dá)。其表達(dá)相當(dāng)普遍，但在脂肪細(xì)胞，脂肪，全腦，胎腦和子宮內(nèi)膜中最高的正常表達(dá)。在一份結(jié)腸腫瘤標(biāo)本中，一份正常肺標(biāo)本中，軟骨細(xì)胞中和未感染的MRC5細(xì)胞中有最高的疾病表達(dá)。在阿爾茨海默氏病患者的腦中沒有明顯的變化。在4份肺腫瘤的1份中下調(diào)提示其可能參與肺癌。在4份乳腺腫瘤標(biāo)本的1份中上調(diào)可足以斷定其在乳腺癌中的作用。在4份哮喘肺的1份中上調(diào)提示其在哮喘中的作用。在HSV中下調(diào)提示其作為潛在的宿主因子與單純皰疹病毒有關(guān)。在免疫細(xì)胞中高表達(dá)。在來自O(shè)A患者的軟骨和骨標(biāo)本中高表達(dá)以及在軟骨細(xì)胞中的高表達(dá)提示其可能參與骨關(guān)節(jié)炎和類風(fēng)濕性關(guān)節(jié)炎。另外，在免疫細(xì)胞中(尤其是B細(xì)胞和T細(xì)胞中)確定的表達(dá)為其在RA/OA中的作用提供了附加的證據(jù)。
基因名稱sbg1151bSREC
基因名稱sbg1399854ANK低度總體表達(dá)。在全腦，胎腦和肝臟可見最高的正常表達(dá)。在代表女性生殖系統(tǒng)的所有標(biāo)本中可見良好的表達(dá)水平。在正常和阿爾茨海默氏病腦標(biāo)本中以及在樹突細(xì)胞中可見最高的疾病表達(dá)。在4份結(jié)腸腫瘤標(biāo)本的2份中上調(diào)和在4份乳腺腫瘤標(biāo)本的2份中上調(diào)，以及在4份肺腫瘤標(biāo)本的2份中下調(diào)提示該基因與結(jié)腸癌，乳腺癌和肺癌有關(guān)。在所有3份COPD標(biāo)本中下調(diào)和在4份哮喘標(biāo)本的2份中下調(diào)提示該基因在慢性阻塞性肺病和哮喘中的潛在作用。在OA的軟骨標(biāo)本中下調(diào)和在正常軟骨細(xì)胞和許多免疫細(xì)胞中的確定的低表達(dá)提示其參與骨關(guān)節(jié)炎。在HSV感染的HRC5細(xì)胞中上調(diào)提示該基因可能是HSV中的宿主因子。

基因名稱sbg1399854ANK
表V.基于特異性組織中mRNA表達(dá)的其它疾病
序列表<110>史密斯克萊恩·比徹姆公司(SMITHKLINE BEECHAM CORPORATION)史密斯克萊·比奇曼生物公司(SMITHKLINE BEECHAM p.l.c.)葛蘭素集團(tuán)有限公司(GLAXO GROUP，LIMITED)<120>新型化合物<130>GP50034<140>TO BE ASSIGNED<141>2001-09-13<150>60/232,463<151>2000-09-13<150>60/232,455<151>2000-09-13<150>60/237,293<151>2000-10-02<150>60/246,269<151>2000-11-07<150>60/252,049<151>2000-11-20<160>88<170>FastSEQ for Windows Version 4.0<210>1<211>1707<212>DNA<213>人(Homo sapiens)<400>1atgaaggaag cagagatgga cggtgaggca gtccgcttct gcacagataa ccagtgtgtc 60tccctgcacc cccaagaggt ggactctgtg gcaatggctc ctgcagcccc caagataccg 120aggctcgttc aggctacccc ggcatttatg gctgtgacct tggtcttctc tcttgtgact 180ctctttgtag tgggtaagcc cccagttcaa cagcagacaa gacctgttcc gaagcctgtg 240caagccgtaa ttctgggaga caacattact gggcatttac cttttgaacc caacaatcat 300caccactttg gcagggaggc agaaatgcga gagcttatcc agacatttaa aggccacatg 360gagaattcca gtgcctgggt agtagaaatc cagatgttga agtgcagagt ggacaatgtc 420aattcgcagc tccaggtgct cggtgatcat ctgggaaaca ccaatgctga catccagatg 480gtaaaaggag ttctaaagga tgccactaca ttgagtttgc agacacagat gttaaggagt 540tccctggagg gaaccaatgc tgagatccag aggctcaagg aagaccttga aaaggcagat 600gctttaactt tccagacgct gaatttctta aaaagcagtt tagaaaacac cagcattgag 660ctccacgtgc taagcagagg cttagaaaat gcaaactctg aaattcagat gttgaatgcc 720agagccaatg ctgagatcca gggactaaag gaaaatttgc agaacacaaa tgctttaaac 780tcccagaccc aggcctttat aaaaagcagt tttgacaaca ctagtgctga gatccagttc 840ttaagaggtc atttggaaag agctggtgat gaaattcacg tgttaaaaag ggatttgaaa 900atggtcacag cccagaccca aaaagcaaat ggccgtctgg accagacaga tactcagatt 960caggtattca agtcagagat ggaaaatgtg aataccttaa atgcccagat tcaggtctta1020aatggtcata tgaaaaatgc cagcagagag atacagaccc taaaacaagg aatgaagaat1080gcttcagcct taacttccca gacccagatg ttagacagca atctgcagaa ggccagtgcc1140gagatccaga ggttaagagg ggatctagag aacaccaaag ctctaaccat ggaaatccag1200caggagcaga gtcgcctgaa gaccctccat gtggtcatta cttcacagga acagctacaa1260agaacccaaa gtcagcttct ccagatggtc ctgcaaggct ggaagttcaa tggtggaagc1320ttatattatt tttctagtgt caagaagtct tggcatgagg ctgagcagtt ctgcgtgtcc1380cagggagccc atctggcatc tgtggcctcc aaggaggagc aggcatttct ggtagagttc1440acaagtaaag tgtactactg gatcggtctc actgacaggg gcacagaggg ctcctggcgc1500tggacagatg ggacaccatt caacgccgcc cagaacaaag cccctgttgt cttcgggttt1560tgggaaaaga atcagtctga caactggcgg cacaagaatg ggcagactga agactgtgtc1620caaattcagc agaagtggaa tgacatgacc tgtgacaccc cctatcagtg ggtgtgcaag1680aagcccatgg gccagggtgt ggcctga 1707<210>2<211>1095<212>DNA<213>人(Homo sapiens)<400>2atgtcgagac aaggaaaatt attttctgct tttggagtgg gttgttgtgt aacggcaggc 60ttgccaaagg acgataacac tcctagcacc attgcggatg tgcacaatgg ttatacgatg 120aatgttgtag agcaagttct aaaggatagt tttgtgttat ttttcccagg aacactttgt 180gattttccaa aaatacacca tggatttctg tatgatgaag aagattataa ccctttttcc 240caagttccta caggggaagt tttctattac tcctgtgaat ataattttgt gtctccttca 300aaatcctttt ggactcgcat aacatgcaca gaagaaggat ggtcaccaac accgaagtgt 360ctcagaatgt gttcctttcc ttttgtgaaa aatggtcatt ctgaatcttc aggactaata 420catctggaag gtgatactgt acaaattatt tgcaacacag gatacagcct tcaaaacaat 480gagaaaaaca tttcgtgtgt agaacggggc tggtccactc ctcccatatg cagcttcact 540atgaaaacat gtggatacat acctgaactc gagtacggtt atgttcagcc gtctgtccct 600ccctatcaac atggagtttc agtcgaggtg aattgcagaa atgaatatgc aatgattgga 660aataacatga ttacctgtat taatggaata tggacagagc ttcctatgtg tgttgagtct 720actgcatatt gtgggccccc tccatctatt aacaatggag ataccacctc attcccatta 780tcagtatatc ctccagggtc aacagtgacg taccgttgcc agtccttcta taaactccag 840ggctctgtaa ctgtaacatg cagaaataaa cagtggtcag aaccaccaag atgcctagat 900ccatgtgtgg tatctgaaga aaacatgaac aaaaataaca tacagttaaa atggagaaac 960gatggaaaac tctatgcaaa aacaggggat gctgttgaat tccagtgtaa attcccacat1020aaagcgatga tatcatcacc accatttcga gcaatctgtc aggaagggaa atttgaatat1080cctatatgtg aatga 1095<210>3<211>984<212>DNA<213>人(Homo sa piens)<400>3atgttgctct tattcagtgt aatcctaatc tcatgggtat ccactgttgg gggagaagga 60acactttgtg attttccaaa aatacaccat ggatttctgt atgatgaaga agattataac 120cctttttccc aagttcctac aggggaagtt ttctattact cctgtgaata taattttgtg 180tctccttcaa aatccttttg gactcgcata acatgcacag aagaaggatg gtcaccaaca 240ccgaagtgtc tcagaatgtg ttcctttcct tttgtgaaaa atggtcattc tgaatcttca 300ggactaatac atctggaagg tgatactgta caaattattt gcaacacagg atacagcctt 360caaaacaatg agaaaaacat ttcgtgtgta gaacggggct ggtccactcc tcccatatgc 420agcttcacta tgaaaacatg tggatacata cctgaactcg agtacggtta tgttcagccg 480tctgtccctc cctatcaaca tggagtttca gtcgaggtga attgcagaaa tgaatatgca 540atgattggaa ataacatgat tacctgtatt aatggaatat ggacagagct tcctatgtgt 600gttgagtcta ctgcatattg tgggccccct ccatctatta acaatggaga taccacctca 660ttcccattat cagtatatcc tccagggtca acagtgacgt accgttgcca gtccttctat 720aaactccagg gctctgtaac tgtaacatgc agaaataaac agtggtcaga accaccaaga 780tgcctagatc catgtgtggt atctgaagaa aacatgaaca aaaataacat acagttaaaa 840tggagaaacg atggaaaact ctatgcaaaa acaggggatg ctgttgaatt ccagtgtaaa 900ttcccacata aagcgatgat atcatcacca ccatttcgag caatctgtca ggaagggaaa 960tttgaatatc ctatatgtga atga984<210>4<211>465<212>DNA<213>人(Homo sapiens)<400>4atggcaccgg ccagagcagg atgctgcccc ctgctgctgc tgcttctggg gctgtgggtg 60gcagaggtcc tagtcagagc caagcccaag gacatgacat catctcagtg gtttaaaact 120cagcatgtgc agcccagccc tcaagcatgc aactcagcca tgagcatcat caataagtac 180acagaacggt gcaaagacct caacaccttc ctgcacgagc ccttctccag tgtggccatc 240acctgccaga cccccaacat agcctgcaag aatagctgta aaaactgcca ccagagccac 300gggcccatgt ccctgaccat gggtgagctc acctcaggga agtacccaaa ctgcaggtac 360aaagagaagc acctgaacac accttacata gtggcctgtg accctccaca acagggtgac 420ccagggtacc cacttgttcc tgtgcacttg gataaagttg tctaa 465<210>5<211>1509<212>DNA<213>人(Homo sapiens)<400>5atgcgccagc tgggagggtc tctccgcccc ccgcgcgcgg cccacggggc cgagcctctc 60cccagtgcgc tggggccctg cgctgggggt gaccgggacc tgggtcgggg aacccccgga 120tgggagccca ggcgcgccag ggtccccatc cacgagcagg tcgacccccc gcgagagggg 180ccccacctct tccagaacct cctgctcttc ctgtgggccc tgctgaactg tggtttgggg 240gtcagtgctc agggtccggg cgagtggacc ccgtgggtgt cctggacccg ctgctccagc 300tcctgcgggc gtggcgtctc tgtgcgcagc cggcgctgcc tccggcttcc tggggaagaa 360ccgtgctggg gagactccca tgagtaccgc ctctgccagt tgccagactg ccccccaggg 420gctgtgccct tccgagacct acagtgtgcc ctgtacaatg gccgccctgt cctgggcacc 480cagaagacct accagtgggt gcccttccat ggggcgccca accagtgcga cctcaactgc 540ctggctgagg ggcacgcctt ctaccacagc ttcggccgcg tcctggacgg caccgcctgc 600agcccgggtg cccagggggt ctgcgtggct ggccgctgcc ttagcgccgg ctgtgatggg 660ttgttgggct cgggtgccct cgaggaccgc tgtggccgct gcggaggcgc caacgactcg 720tgccttttcg tgcagcgcgt gtttcgtgac gccggtgcct tcgctgggta ctggaacgtg 780accctgatcc ccgagggcgc cagacacatc cgcgtggaac acaggagccg caaccacctg 840ggtatcctag gatcactgat ggggggcgat gggcgctacg tgcttaatgg gcactgggtg 900gtcagcccac cagggaccta cgaggcggcc ggcacgcatg tggtctacac ccgagacaca 960gggccccagg agacattgca agcagccggg cccacctccc atgacctgct cctacaggtc1020ctcctgcagg agcccaaccc tggcatcgag tttgagttct ggctccctcg ggagcgctac1080agccccttcc aggctcgtgt gcaggccctg ggctggcccc tgaggcagcc tcagccccgg1140ggggtggagc ctcagccccc cgcagcccct gctgtcaccc ctgcacagac cccaacgctg1200gccccagtgt tccaggcccg agtgctgggc caccaccacc aggcccagga gacccgctat1260gaggtgcgca tccagctcgt ctacaagaac cgctcgccac tgcgggcacg cgagtacgtg1320tgggcgccag gccactgccc ctgcccgatg ctggcacccc accgggacta cctgatggct1380gtccagcgtc ttgtcagccc cgacggcaca caggaccagc tgctgctgcc ccacgccggc1440tacgcccggc cctggagccc tgcggaggac agccgcatac gcctgactgc ccggcgctgt1500cctggctga1509<210>6<211>1356<212>DNA<213>人(Homo sapiens)<400>6atggactcgg cccctctgtt ccccaggccc cacctcttcc agaacctcct gctcttcctg 60tgggccctgc tgaactgtgg tttgggggtc agtgctcagg gtccgggcga gtggaccccg 120tgggtgtcct ggacccgctg ctccagctcc tgcgggcgtg gcgtctctgt gcgcagccgg 180cgctgcctcc ggcttcctgg ggaagaaccg tgctggggag actcccatga gtaccgcctc 240tgccagttgc cagactgccc cccaggggct gtgcccttcc gagacctaca gtgtgccctg 300tacaatggcc gccctgtcct gggcacccag aagacctacc agtgggtgcc cttccatggg 360gcgcccaacc agtgcgacct caactgcctg gctgaggggc acgccttcta ccacagcttc 420ggccgcgtcc tggacggcac cgcctgcagc ccgggtgccc agggggtctg cgtggctggc 480cgctgcctta gcgccggctg tgatgggttg ttgggctcgg gtgccctcga ggaccgctgt 540ggccgctgcg gaggcgccaa cgactcgtgc cttttcgtgc agcgcgtgtt tcgtgacgcc 600ggtgccttcg ctgggtactg gaacgtgacc ctgatccccg agggcgccag acacatccgc 660gtggaacaca ggagccgcaa ccacctgggt atcctaggat cactgatggg gggcgatggg 720cgctacgtgc ttaatgggca ctgggtggtc agcccaccag ggacctacga ggcggccggc 780acgcatgtgg tctacacccg agacacaggg ccccaggaga cattgcaagc agccgggccc 840acctcccatg acctgctcct acaggtcctc ctgcaggagc ccaaccctgg catcgagttt 900gagttctggc tccctcggga gcgctacagc cccttccagg ctcgtgtgca ggccctgggc 960tggcccctga ggcagcctca gccccggggg gtggagcctc agccccccgc agcccctgct 1020gtcacccctg cacagacccc aacgctggcc ccagtgttcc aggcccgagt gctgggccac 1080caccaccagg cccaggagac ccgctatgag gtgcgcatcc agctcgtcta caagaaccgc 1140tcgccactgc gggcacgcga gtacgtgtgg gcgccaggcc actgcccctg cccgatgctg 1200gcaccccacc gggactacct gatggctgtc cagcgtcttg tcagccccga cggcacacag 1260gaccagctgc tgctgcccca cgccggctac gcccggccct ggagccctgc ggaggacagc 1320cgcatacgcc tgactgcccg gcgctgtcct ggctga 1356<210>7<211>1296<212>DNA<213>人(Homo sapiens)<400>7atgatccgga ccccattgtc ggcctctgcc catcgcctgc tcctcccagg ctcccgcggc 60cgacccccgc gcaacatgca gcccacgggc cgcgagggtt cccgcgcgct cagccggcgg 120tatctgcggc gtctgctgct cctgctactg ctgctgctgc tgcggcagcc cgtaacccgc 180gcggagacca cgccgggcgc ccccagagcc ctctccacgc tgggctcccc cagcctcttc 240accacgccgg gtgtccccag cgccctcact accccaggcc tcactacgcc aggcaccccc 300aaaaccctgg accttcgggg tcgcgcgcag gccctgatgc ggagtttccc actcgtggac 360gggtatgtag gtctgaacag ctctcaaaag ctggcctgcc tcattggcgt ggagggtggt 420cactcactgg acagcagcct ctctgtgctg cgcagtttct atgtgctggg ggtgcgctac 480ctgacactta ccttcacctg cagtacacca tgggcagaga gttccaccaa gttcagacac 540cacatgtaca ccaacgtcag cggattgaca agctttggtg agaaagtagt agaggagttg 600aaccgcctgg gcatgatgat agatttgtcc tatgcatcgg acaccttgat aagaagggtc 660ctggaagtgt ctcaggctcc tgtgatcttc tcccactcag ctgccagagc tgtgtgtgac 720aatttgttga atgttcccga tgatatcctg cagcttctga agaagaacgg tggcatcgtg 780atggtgacac tgtccatggg ggtgctgcag tgcaacctgc ttgctaacgt gtccactgtg 840gcagatgatt cgaatcgatg ctcggtaccc gtcattggat ctgagttcat cgggattggt 900ggaaattatg acgggactgg ccggttccct caggggctgg aggatgtgtc cacataccca 960gtcctgatag aggagttgct gagtcgtagc tggagcgagg aagagcttca aggtgtcctt1020cgtggaaacc tgctgcgggt cttcagacaa gtggaaaagg tgagagagga gagcagggcg1080cagagccccg tggaggctga gtttccatat gggcaactga gcacatcctg ccactcccac1140ctcgtgcctc agaatggaca ccaggctact catctggagg tgaccaagca gccaaccaat1200cgggtcccct ggaggtcctc aaatgcctcc ccataccttg ttccaggcct tgtggctgct1260gccaccatcc caaccttcac ccagtggctc tgctga 1296<210>8<211>1443<212>DNA<213>人(Homo sapiens)<400>8atgcagccct ccggcctcga gggtcccggc acgtttggtc ggtggcctct gctgagtctg 60ctgctcctgc tgctgctgct ccagcctgta acctgtgcct acaccacgcc aggccccccc 120agagccctca ccacgctggg cgcccccaga gcccacacca tgccgggcac ctacgctccc 180tcgaccacac tcagtagtcc cagcacccag ggcctgcaag agcaggcacg ggccctgatg 240cgggacttcc cgctcgtgga cggccacaac gacctgcccc tggtcctaag gcaggtttac 300cagaaagggc tacaggatgt taacctgcgc aatttcagct acggccagac cagcctggac 360aggcttagag atggcctcgt gggcgcccag ttctggtcag cctatgtgcc atgccagacc 420caggaccggg atgccctgcg cctcaccctg gagcagattg acctcatacg ccgcatgtgt 480gcctcctatt ctgagctgga gcttgtgacc tcggctaaag gtctgaacag ctctcaaaag 540ctggcctgcc tcattggcgt ggagggtggt cactcactgg acagcagcct ctctgtgctg 600cgcagtttct atgtgctggg ggtgcgctac ctgacactta ccttcacctg cagtacacca 660tgggcagaga gttccaccaa gttcagacac cacatgtaca ccaacgtcag cggattgaca 720agctttggtg agaaagtagt agaggagttg aaccgcctgg gcatgatgat agatttgtcc 780tatgcatcgg acaccttgat aagaagggtc ctggaagtgt ctcaggctcc tgtgatcttc 840tcccactcag ctgccagagc tgtgtgtgac aatttgttga atgttcccga tgatatcctg 900cagcttctga agaagaacgg tggcatcgtg atggtgacac tgtccatggg ggtgctgcag 960tgcaacctgc ttgctaacgt gtccactgtg gcagatcact ttgaccacat cagggcagtc1020attggatctg agttcatcgg gattggtgga aattatgacg ggactggccg gttccctcag1080gggctggagg atgtgtccac atacccagtc ctgatagagg agttgctgag tcgtagctgg1140agcgaggaag agcttcaagg tgtccttcgt ggaaacctgc tgcgggtctt cagacaagtg1200gaaaaggtga gagaggagag cagggcgcag agccccgtgg aggctgagtt tccatatggg1260caactgagca catcctgcca ctcccacctc gtgcctcaga atggacacca ggctactcat1320ctggaggtga ccaagcagcc aaccaatcgg gtcccctgga ggtcctcaaa tgcctcccca1380taccttgttc caggccttgt ggctgctgcc accatcccaa ccttcaccca gtggctctgc1440tga 1443<210>9<211>1116<212>DNA<213>人(Homo sapiens)<400>9atggatgcag ccacagctcc aaagcaagcc tggcccccat ggcccccgct ccttttcctc 60ctcctcctac ctggagggag cggtggcagc tgccctgctg tgtgtgactg cacctcccag 120ccccaggctg tgctctgtgg ccacaggcaa ctggaggctg tacctggagg actcccactg 180gacactgagc tcctggacct gagtgggaac cgcctcccga aggctcagcc cctggtgcgg 240ctccaggagc tacgcctgtc aggggcatgc ctcacctcca ttgctgccca tgccttccat 300ggcttgactg ccttccacct cctggatgtg gcagataacg cccttcagac actagaggaa 360acagctttcc cttctccaga caaactggtc accttgaggc tgtctggcaa ccccctaacc 420tgtgactgcc gcctcctctg gctgctccgg ctccgccacc tggactttgg catgtccccc 480cctgcctgtg ctggccccca tcatgtccag gggaagagcc tgaaggagtt ttcagacatc 540ctgcctccag ggcacttcac ctgcaaacca gccctgatcc gaaagtcggg gcctcgatgg 600gtcattgcag aggagggcgg gcatgcggtt ttctcctgct ctggagatgg agacccagcc 660cccactgtct cctggatgag gcctcatggg gcttggctgg gcagggctgg gagagtaagg 720gtcctagagg atgggacact ggagatccgc tcagtgcagc tacgggacag aggggcctat 780gtctgtgtgg ttagcaatgt cgctgggaat gactccctga ggacctggct ggaagtcatc 840caggtggaac caccaaacgg cacactttct gaccccaaca tcaccgtgcc agggatccca 900gggccttttt ttctggatag cagaggtgtg gccatggtgc tggcagtcgg cttcctcccc 960ttcctcacct cagtgaccct ctgctttggc ctgattgccc tttggagcaa gggcaaaggt1020cgggtcaaac atcacatgac ctttgacttt gtggcacctc ggccctctgg ggataaaaac1080tctgggggta accgggtcac tgccaagctc ttctga 1116<210>10<211>1779<212>DNA<213>人(Homo sapiens)<400>10atggatgcag ccacagctcc aaagcaagcc tggcccccat ggcccccgct ccttttcctc 60ctcctcctac ctggagggag cggtggcagc tgccctgctg tgtgtgactg cacctcccag 120ccccaggctg tgctctgtgg ccacaggcaa ctggaggctg tacctggagg actcccactg 180gacactgagc tcctggacct gagtgggaac cgcctgtggg ggctccagca gggaatgctc 240tcccgcctga gcctgctcca ggaattggac ctcagctaca accagctctc aacccttgag 300cctggggcct tccatggcct acaaagccta ctcaccctga ggctgcaggg caatcggctc 360agaatcatgg ggcctggggt cttctcaggc ctctctgctc tgaccctgct ggacctccgc 420ctcaaccaga ttgttctctt cctagatgga gcttttgggg agctaggcag cctccagaag 480ctggaggttg gggacaacca cctggtattt gtggctccgg gggcctttgc agggctagcc 540aagttgagca ccctcaccct ggagcgctgc aacctcagca cagtgcctgg cctagccctt 600gcccgtctcc cggcactagt ggccctaagg cttagagaac tggatattgg gaggctgcca 660gctggggccc tgcgggggct ggggcagctc aaggagctgg agatccacct ctggccatct 720ctggaggctc tggaccctgg gagcctggtt gggctcaatc tcagcagcct ggccatcact 780cgctgcaatc tgagctcggt gcccttccaa gcactgtacc acctcagctt cctcagggtc 840ctggatctgt cccagaatcc catctcagcc atcccagccc gaaggctcag ccccctggtg 900cggctccagg agctacgcct gtcaggggca tgcctcacct ccattgctgc ccatgccttc 960catggcttga ctgccttcca cctcctggat gtggcagata acgcccttca gacactagag1020gaaacagctt tcccttctcc agacaaactg gtcaccttga ggctgtctgg caacccccta1080acctgtgact gccgcctcct ctggctgctc cggctccgcc acctggactt tggcatgtcc1140ccccctgcct gtgctggccc ccatcatgtc caggggaaga gcctgaagga gttttcagac1200atcctgcctc cagggcactt cacctgcaaa ccagccctga tccgaaagtc ggggcctcga1260tgggtcattg cagaggaggg cgggcatgcg gttttctcct gctctggaga tggagaccca1320gcccccactg tctcctggat gaggcctcat ggggcttggc tgggcagggc tgggagagta1380agggtcctag aggatgggac actggagatc cgctcagtgc agctacggga cagaggggcc1440tatgtctgtg tggttagcaa tgtcgctggg aatgactccc tgaggacctg gctggaagtc1500atccaggtgg aaccaccaaa cggcacactt tctgacccca acatcaccgt gccagggatc1560ccagggcctt tttttctgga tagcagaggt gtggccatgg tgctggcagt cggcttcctc1620cccttcctca cctcagtgac cctctgcttt ggcctgattg ccctttggag caagggcaaa1680ggtcgggtca aacatcacat gacctttgac tttgtggcac ctcggccctc tggggataaa1740aactctgggg gtaaccgggt cactgccaag ctcttctga 1779<210>11<211>429<212>DNA<213>人(Homo sapiens)<400>11atggccaggt acatgctgct gctgctcctg gcggtatggg tgctgaccgg ggagctgtgg 60ccgggagctg aggcccgggc agcgccttac ggggtcaggc tttgcggccg agaattcatc 120cgagcagtca tcttcacctg cgggggctcc cggtggagac gatcagacat cctggcccac 180gaggctatgg gagatacctt cccggatgca gatgctgatg aagacagtct ggcaggcgag 240ctggatgagg ccatggggtc cagcgagtgg ctggccctga ccaagtcacc ccaggccttt 300tacagggggc gacccagctg gcaaggaacc cctggggttc ttcggggcag ccgagatgtc 360ctggctggcc tttccagcag ctgctgcaag tgggggtgta gcaaaagtga aatcagtagc 420ctttgctag 429<210>12<211>692<212>DNA<213>人(Homo sapiens)<400>12atgtctgaag aagtgaccta cgcgacactc acatttcagg attctgctgg agcaaggaat 60aaccgagatg gaaataacct aagaaaaaga gggcatccag ctccatctcc catttggcgt 120catgctgctc tgggtctggt aactctttgc ctgatgttgc tgattgggct ggtgacgttg 180gggatgatgt ttttgcagat atctaatgac attaactcag attcagagaa attgagtcaa 240cttcagaaaa ccatccaaca gcagcaggat aacttatccc agcaactggg caactccaac 300aacttgtcca tggaggagga atttctcaag tcacagatct ccagtctact gaagaggcag 360gaacaaatgg ccatcaaact gtgccaagag ctaatcattc atacttcaga ccacagatgt 420aatccatgtc ctaagatgtg gcaatggtac caaaatagtt gctactattt tacaacaaat 480gaggagaaaa cctgggctaa cagtagaaag gactgcatag acaagaactc caccctagtg 540aagatagaca gtttggaaga aaaggatttt cttatgtcac agccattact catgttttcg 600ttcttttggc tgggattatc atgggactcc tctggcagaa gttggttctg ggaagatggc 660tctgttccct ctccatcctt gtacgtctct aa 692<210>13<211>585<212>DNA<213>人(Homo sapiens)<400>13atgtggctgt ccccagctct gctgcttctc atcctcccag gttactccat tgccgctaaa 60atcactggtc caacaacagt gaatggctcg gagcagggct cattgactgt gcagtgtgct 120tatggctcag gctgggagac ctacttgaag tggcggtgtc aaggagctga ttggaattac 180tgtaacatcc ttgttaaaac aaatggatca gagcaggagg taaagaagaa tcgagtttcc 240atcagggaca atcagaaaaa ccacatgttc accgtgacca tggagaatct caaaagagat 300gatgctgaca gttattggtg tgggactgag agacctggaa ttgatcttgg ggtcaaagtt 360caagtgacca ttaacccagg cacacaaact gcagtctcag aatggacaac cacaacagca 420agcctggctt tcacagctgc agccacccag aagaccagca gccccctcac caggtccccg 480ctcaagagca cccacttcct gttcctgttc ctcctggagc tgcctctgct cctgagcatg 540ctggggaccg tcctctgggt gaacagacca caaagaaggt cttga 585<210>14<211>1002<212>DNA<213>人(Homo sapiens)<400>14atgaggatct ggtggcttct gcttgccatt gaaatctgca cagggaacat aaactcacag 60gacacctgca ggcaagggca ccctggaatc cctgggaacc ccggtcacaa tggtctgcct 120ggaagagatg gacgagacgg agcgaagggt gacaaaggcg atgcaggaga accaggacgt 180cctggcagcc cggggaagga tgggacgagt ggagagaagg gagaacgagg agcagatgga 240aaagttgaag caaaaggcat caaaggtgat caaggctcaa gaggatcccc aggaaaacat 300ggccccaagg ggcttgcagg gcccatggga gagaagggcc tccgaggaga gactgggcct 360caggggcaga aggggaataa gggtgacgtg ggtcccactg gtcctgaggg gccaaggggc 420aacattgggc ctttgggccc aactggttta ccgggcccca tgggccctat tggaaagcct 480ggtcccaaag gagaagctgg acccacgggg ccccagggtg agccaggagt ccggggaata 540agaggctgga aaggagatcg aggagagaaa gggaaaatcg gtgagactct agtcttgcca 600aaaagtgctt tcactgtggg gctcacggtg ctgagcaagt ttccttcttc agatatgccc 660attaaatttg ataagatcct gtataacgaa ttcaaccatt atgatacagc agcggggaaa 720ttcacgtgcc acattgctgg ggtctattac ttcacctacc acatcactgt tttctccaga 780aatgttcagg tgtctttggt caaaaatgga gtaaaaatac tgcacaccaa agatgcttac 840atgagctctg aggaccaggc ctctggcggc attgtcctgc agctgaagct cggggatgag 900gtgtggctgc aggtgacagg aggagagagg ttcaatggct tgtttgctga tgaggacgat 960gacacaactt tcacagggtt ccttctgttc agcagcccgt ga 1002<210>15<211>678<212>DNA<213>人(Homo sapiens)<400>15atgaggatct ggtggcttct gcttgccatt gaaatctgca cagggaacat aaactcacag 60gacacctgca ggcaagggca ccctggaatc cctgggaacc ccggtcacaa tggtctgcct120ggaagagatg gacgagacgg agcgaagggt gacaaaggcg atgcaggaga agctggaccc180acggggcccc agggtgagcc aggagtccgg ggaataagag gctggaaagg agatcgagga240gagaaaggga aaatcggtga gactctagtc ttgccaaaaa gtgctttcac tgtggggctc300acggtgctga gcaagtttcc ttcttcagat atgcccatta aatttgataa gatcctgtat360aacgaattca accattatga tacagcagcg gggaaattca cgtgccacat tgctggggtc420tattacttca cctaccacat cactgttttc tccagaaatg ttcaggtgtc tttggtcaaa480aatggagtaa aaatactgca caccaaagat gcttacatga gctctgagga ccaggcctct540ggcggcattg tcctgcagct gaagctcggg gatgaggtgt ggctgcaggt gacaggagga600gagaggttca atggcttgtt tgctgatgag gacgatgaca caactttcac agggttcctt660ctgt tcagca gcccgtga 678<210>16<211>618<212>DNA<213>人(Homo sapiens)<400>16atgatgagaa ctctcatcac cacacaccca ctgcccctgc ttctattgcc gcagcagctg 60ctgcagctgg tgcagtttca agaggtggat acagattttg atttcccaga agaagataaa120aaagaagaat ttgaagagtg tttggaaaaa ttttttagta cagggcccgc cagaccacct180accaaagaaa aagtcaaaag acgtgtcctt attgaacctg gaatgccact aaatcatata240gagtactgta accatgaaat catgggaaaa aatgtttact acaaacaccg ttgggtggca300gaacattact tccttcttat gcaatatgac gagctccaaa aaatctgtta caacagattt360gtgccatgta agaatggaat taggaaatgt aacaggagca aaggtcttgt agaaggagtg420tattgtaatt taacagaagc atttgaaata ccagcgtgta aatacgaatc actttatagg480aagggctacg tccttatcac ttgttcatgg caaaatgaaa tgcaaaaacg tattcctcat540actataaatg atctcgtgga gccacctgaa cacagaagtt tcctcagtga ggatggtgtc600tttgtcatat cgccctag 618<210>17<211>288<212>DNA<213>人(Homo sapiens)<400>17atggaggtgg tgctgatctt tctatgcagc ctgttggccc acattgtcct ggccgatgca 60gttgagaggg agaagcaaat tgaccctttt cattatgact accagaccct gaggattagg120gggttggtat gtgctgtggt cctcttctcc attgggatcc tccttatcct aggttgcaga180tgcaagtgca gtttcaatca gaagcccagg accccaggag aggaggaagc ccaggtggag240aacctcatca ctgcaaatgc aacaaagctc cagaaagcag agagctga 288<210>18<211>1788<212>DNA<213>人(Homo sapiens)<400>18atggaggtgg gaatgggatg ctgggcccgg gaggtgctgg tccccgaggg gcccttgtac 60cgcgtggctg gcacagctgt ctccatctcc tgcaatgtga ccggctatga gggccctgcc120cagcagaact tcgagtggtt cctgtatagg cccgaggccc cagatactgc actgggcatt180gtcagtacca aggataccca gttctcctat gctgtcttca agtcccgagt ggtggcgggt240gaggtgcagg tgcagcgcct acaaggtgat gccgtggtgc tcaagattgc ccgcctgcag300gcccaggatg ccggcattta tgagtgccac accccctcca ctgatacccg ctacctgggc360agctacagcg gcaaggtgga gctgagagtt cttccagatg tcctccaggt gtctgctgcc420cccccagggc cccgaggccg ccaggcccca acctcacccc cacgcatgac ggtgcatgag480gggcaggagc tggcactggg ctgcctggcg aggacaagca cacagaagca cacacacctg540gcagtgtcct ttgggcgatc tgtgcccgag gcaccagttg ggcggtcaac tctgcaggaa600gtggtgggaa tccggtcaga cttggccgtg gaggctggag ctccctatgc tgagcgattg660gctgcagggg agcttcgtct gggcaaggaa gggaccgatc ggtaccgcat ggtagtaggg720ggtgcccagg caggggacgc aggcacctac cactgcactg ccgctgagtg gattcaggat 780cctgatggca gctgggccca gattgcagag aaaagggccg tcctggccca cgtggatgtg 840cagacgctgt ccagccagct ggcagtgaca gtggggcctg gtgaacgtcg gatcggccca 900ggggagccct tggaactgct gtgcaatgtg tcaggggcac ttcccccagc aggccgtcat 960gctgcatact ctgtaggttg ggagatggca cctgcggggc acctggggcc cggccgcctg1020gtagcccagc tggacacaga gggtgtgggc agcctgggcc ctggctatga gggccgacac1080attgccatgg agaaggtggc atccagaaca taccggctac ggctagaggc tgccaggcct1140ggtgatgcgg gcacctaccg ctgcctcgcc aaagcctatg ttcgagggtc tgggacccgg1200cttcgtgaag cagccagtgc ccgttcccgg cctctccctg tacatgtgcg ggaggaaggt1260gtggtgctgg aggctgtggc atggctagca ggaggcacag tgtaccgcgg ggagactgcc1320tccctgctgt gcaacatctc tgtgcggggt ggccccccag gactgcggct ggccgccagc1380tggtgggtgg agcgaccaga ggacggagag ctcagctctg tccctgccca gctggtgggt1440ggcgtaggcc aggatggtgt ggcagagctg ggagtccggc ctggaggagg ccctgtcagc1500gtagagctgg tggggccccg aagccatcgg ctgagactac acagcttggg gcccgaggat1560gaaggcgtgt accactgtgc ccccagcgcc tgggtgcagc atgccgacta cagctggtac1620caggcgggca gtgcccgctc agggcctgtt acagtctacc cctacatgca tgccctggac1680accctatttg tgcctctgct ggtgggtaca ggggtggccc tagtcactgg tgccactgtc1740cttggtacca tcacttgctg cttcatgaag aggcttcgaa aacggtga 1788<210>19<211>1842<212>DNA<213>人(Homo sapiens)<400>19atgggcgccc tcaggcccac gctgctgccg ccttcgctgc cgctgctgct gctgctaatg 60ctaggaatgg gatgctgggc ccgggaggtg ctggtccccg aggggccctt gtaccgcgtg 120gctggcacag ctgtctccat ctcctgcaat gtgaccggct atgagggccc tgcccagcag 180aacttcgagt ggttcctgta taggcccgag gccccagata ctgcactggg cattgtcagt 240accaaggata cccagttctc ctatgctgtc ttcaagtccc gagtggtggc gggtgaggtg 300caggtgcagc gcctacaagg tgatgccgtg gtgctcaaga ttgcccgcct gcaggcccag 360gatgccggca tttatgagtg ccacaccccc tccactgata cccgctacct gggcagctac 420agcggcaagg tggagctgag agttcttcca gatgtcctcc aggtgtctgc tgccccccca 480gggccccgag gccgccaggc cccaacctca cccccacgca tgacggtgca tgaggggcag 540gagctggcac tgggctgcct ggcgaggaca agcacacaga agcacacaca cctggcagtg 600tcctttgggc gatctgtgcc cgaggcacca gttgggcggt caactctgca ggaagtggtg 660ggaatccggt cagacttggc cgtggaggct ggagctccct atgctgagcg attggctgca 720ggggagcttc gtctgggcaa ggaagggacc gatcggtacc gcatggtagt agggggtgcc 780caggcagggg acgcaggcac ctaccactgc actgccgctg agtggattca ggatcctgat 840ggcagctggg cccagattgc agagaaaagg gccgtcctgg cccacgtgga tgtgcagacg 900ctgtccagcc agctggcagt gacagtgggg cctggtgaac gtcggatcgg cccaggggag 960cccttggaac tgctgtgcaa tgtgtcaggg gcacttcccc cagcaggccg tcatgctgca1020tactctgtag gttgggagat ggcacctgcg ggggcacctg ggcccggccg cctggtagcc1080cagctggaca cagagggtgt gggcagcctg ggccctggct atgagggccg acacattgcc1140atggagaagg tggcatccag aacataccgg ctacggctag aggctgccag gcctggtgat1200gcgggcacct accgctgcct cgccaaagcc tatgttcgag ggtctgggac ccggcttcgt1260gaagcagcca gtgcccgttc ccggcctctc cctgtacatg tgcgggagga aggtgtggtg1320ctggaggctg tggcatggct agcaggaggc acagtgtacc gcggggagac tgcctccctg1380ctgtgcaaca tctctgtgcg gggtggcccc ccaggactgc ggctggccgc cagctggtgg1440gtggagcgac cagaggacgg agagctcagc tctgtccctg cccagctggt gggtggcgta1500ggccaggatg gtgtggcaga gctgggagtc cggcctggag gaggccctgt cagcgtagag1560ctggtggggc cccgaagcca tcggctgaga ctacacagct tggggcccga ggatgaaggc1620gtgtaccact gtgcccccag cgcctgggtg cagcatgccg actacagctg gtaccaggcg1680ggcagtgccc gctcagggcc tgttacagtc tacccctaca tgcatgccct ggacacccta1740tttgtgcctc tgctggtggg tacaggggtg gccctagtca ctggtgccac tgtccttggt1800accatcactt gctgcttcat gaagaggctt cgaaaacggt ga 1842<210>20<211>1791<212>DNA<213>人(Homo sapiens)<400>20atggccgcca actccaccag cgacctccac actcccggga cgcagctgag cgtggctgac 60atcatcgtca tcactgtgta ttttgctctg aacgtggccg tgggcatatg gtcctcttgt 120cgggccagta ggaacacggt gaatggctac ttcctggcag gccgggacat gacgtggtgg 180ccgattggag cctccctctt cgccagcagc gagggctctg gcctcttcat tggactggcg 240ggctcaggcg cggcaggagg tctggccgtg gcaggcttcg agtggaatgc cacgtacgtg 300ctgctggcac tggcatgggt gttcgtgccc atctacatct cctcagagat cgtcacctta 360cctgagtaca ttcagaagcg ctacgggggc cagcggatcc gcatgtacct gtctgtcctg 420tccctgctac tgtctgtctt caccaagata tcgctggacc tgtacgcggg ggctctgttt 480gtgcacatct gcctgggctg gaacttctac ctctccacca tcctcacgct cggcatcaca 540gccctgtaca ccatcgcagg gggcctggct gctgtaatct acacggacgc cctgcagacg 600ctcatcatgg tggtgggggc tgtcatcctg acaatcaaag cttttgacca gatcggtggt 660tacgggcagc tggaggcagc ctacgcccag gccattccct ccaggaccat tgccaacacc 720acctgccacc tgccacgtac agacgccatg cacatgtttc gagaccccca cacaggggac 780ctgccgtgga ccgggatgac ctttggcctg accatcatgg ccacctggta ctggtgcacc 840gaccaggtca tcgtgcagcg atcactgtca gcccgggacc tgaaccatgc caaggcgggc 900tccatcctgg ccagctacct caagatgctc cccatgggcc tgatcataat gccgggcatg 960atcagccgcg cattgttccc agatgatgtg ggctgcgtgg tgccgtccga gtgcctgcgg1020gcctgcgggg ccgaggtcgg ctgctccaac atcgcctacc ccaagctggt catggaactg1080atgcccatcg gtctgcgggg gctgatgatc gcagtgatgc tggcggcgct catgtcgtcg1140ctgacctcca tcttcaacag cagcagcacc ctcttcacta tggacatctg gaggcggctg1200cgtccccgct ccggcgagcg ggagctcctg ctggtgggac ggctggtcat agtggcactc1260atcggcgtga gtgtggcctg gatccccgtc ctgcaggact ccaacagcgg gcaactcttc1320atctacatgc agtcagtgac cagctccctg gccccaccag tgactgcagt ctttgtcctg1380ggcgtcttct ggcgacgtgc caacgagcag ggggccttct ggggcctgat agcagggctg1440gtggtggggg ccacgaggct ggtcctggaa ttcctgaacc cagccccacc gtgcggagag1500ccagacacgc ggccagccgt cctggggagc atccactacc tgcacttcgc tgtcgccctc1560tttgcactca gtggtgctgt tgtggtggct ggaagcctgc tgaccccacc cccacagagt1620gtccagattg agaaccttac ctggtggacc ctggctcagg atgtgccctt gggaactaaa1680gcaggtgatg gccaaacacc ccagaaacac gccttctggg cccgtgtctg tggcttcaat1740gccatcctcc tcatgtgtgt caacatattc ttttatgcct acttcgcctg a 1791<210>21<211>1182<212>DNA<213>人(Homo sapiens)<400>21atggattcct taaagaatga gaactatgat ctggtatttg ttgaagcatt tgatttctgt 60tctttcctga ttgctgagaa gcttgtgaaa ccatttgtgg ccattcttcc caccacattc 120ggctctttgg attttgggct accaagcccc ttgtcttatg ttccagtatt cccttccttg 180ctgactgatc acatggactt ctggggccga gtgaagaatt ttctgatgtt ctttagtttc 240tccaggagcc aatgggacat gcagtctaca tttgacaaca ccatcaagga gcatttccca 300gaaggctcta ggccagtttt gtctcatctt ctactgaaag cagagttgtg gtttgttaac 360tctgattttg cctttgattt tgcccggccc ctgcttccca acactgttta tattggaggc 420ttgatggaaa aacctattaa accagtacca caagacttgg acaacttcat tgccaacttt 480ggggatgcag ggtttgtcct tgtggccttt ggctccatgt tgaacaccca tcagtcccag 540gaagtcctca agaagatgca caatgccttt gcccacctcc ctcaaggagt gatatggaca 600tgtcagagtt ctcattggcc cagagatgtt catttggcca caaatgtgaa aattgtggac 660tggcttcctc agagtgacct cctggctcac cccagcatcc gtctttttgt cactcatggt 720gggcagaaca gcgtaatgga ggccatccgt catggtgtgc ccatggtggg attaccagtc 780aatggagacc agcatggaaa catggtccga gtagtagcca aaaattatgg tgtctctatc 840cggttgaatc aggtcacagc cgacacactg acacttacaa tgaaacaagt catagaagac 900aagaggtaca agtcggcagt ggtggcagcc agtgtcatcc tgcactctca gcccctgagc 960cccgcacagc ggctggtggg ctggatcgac cacatcctcc agactggggg agcgacgcac1020ctcaagccct atgccttcca gcagccttgg catgagcagt acctcattga tgtctttgtg1080tttctgctgg ggctcactct gggcactatg tggctttgtg ggaagctgct gggtgtggtg1140gccaggtggc tgcgtggggc caggaaggtg aagaagacat ga 1182<210>22<211>1572<212>DNA<213>人(Homo sapiens)<400>22atggttgggc agcgggtgct gcttctagtg gccttccttc tttctggggt cctgctctca 60gaggctgcca aaatcctgac aatatctaca ctgggtggaa gccattacct actgttggac 120cgggtgtctc agattcttca agagcatggt cataatgtga ctatgcttca tcagagtgga 180aagtttttga tcccagatat taaagaggag gaaaaatcat accaagttat caggtggttt 240tcacctgaag atcatcaaaa aagaattaag aagcattttg atagctacat agaaacagca 300ttggatggca gaaaagaatc tgaagccctt gtaaagctaa tggaaatatt tgggactcaa 360tgtagttatt tgctaagcag aaaggatata atggattcct taaagaatga gaactatgat 420ctggtatttg ttgaagcatt tgatttctgt tctttcctga ttgctgagaa gcttgtgaaa 480ccatttgtgg ccattcttcc caccacattc ggctctttgg attttgggct accaagcccc 540ttgtcttatg ttccagtatt cccttccttg ctgactgatc acatggactt ctggggccga 600gtgaagaatt ttctgatgtt ctttagtttc tccaggagcc aatgggacat gcagtctaca 660tttgacaaca ccatcaagga gcatttccca gaaggctcta ggccagtttt gtctcatctt 720ctactgaaag cagagttgtg gtttgttaac tctgattttg cctttgattt tgcccggccc 780ctgcttccca acactgttta tattggaggc ttgatggaaa aacctattaa accagtacca 840caagacttgg acaacttcat tgccaacttt ggggatgcag ggtttgtcct tgtggccttt 900ggctccatgt tgaacaccca tcagtcccag gaagtcctca agaagatgca caatgccttt 960gcccacctcc ctcaaggagt gatatggaca tgtcagagtt ctcattggcc cagagatgtt1020catttggcca caaatgtgaa aattgtggac tggcttcctc agagtgacct cctggctcac1080cccagcatcc gtctttttgt cactcatggt gggcagaaca gcgtaatgga ggccatccgt1140catggtgtgc ccatggtggg attaccagtc aatggagacc agcatggaaa catggtccga1200gtagtagcca aaaattatgg tgtctctatc cggttgaatc aggtcacagc cgacacactg1260acacttacaa tgaaacaagt catagaagac aagaggtaca agtcggcagt ggtggcagcc1320agtgtcatcc tgcactctca gcccctgagc cccgcacagc ggctggtggg ctggatcgac1380cacatcctcc agactggggg agcgacgcac ctcaagccct atgccttcca gcagccttgg1440catgagcagt acctcattga tgtctttgtg tttctgctgg ggctcactct gggcactatg1500tggctttgtg ggaagctgct gggtgtggtg gccaggtggc tgcgtggggc caggaaggtg1560aagaagacat ga1572<210>23<211>759<212>DNA<213>人(Homo sapiens)<400>23atgagctgcg tcctgggtgg tgtcatcccc ttggggctgc tgttcctggt ctgcggatcc 60caaggctacc tcctgcccaa cgtcactctc ttagaggagc tgctcagcaa ataccagcac 120aacgagtctc actcccgggt ccgcagagcc atccccaggg aggacaagga ggagatcctc 180atgctgcaca acaagcttcg gggccaggtg cagcctcagg cctccaacat ggagtacatg 240acctgggatg acgaactgga gaagtctgct gcagcgtggg ccagtcagtg catctgggag 300cacgggccca ccagtctgct ggtgtccatc gggcagaacc tgggcgctca ctggggcagg 360tatcgctctc cggggttcca tgtgcagtcc tggtatgacg aggtgaagga ctacacctac 420ccctacccga gcgagtgcaa cccctggtgt ccagagaggt gctcggggcc catgtgcacg 480cactacacac agatagtttg ggccaccacc aacaagatcg gttgtgctgt gaacacctgc 540cggaagatga ctgtctgggg agaagtttgg gagaacgcgg tctactttgt ctgcaattat 600tctccaaagg ggaactggat tggagaagcc ccctacaaga atggccggcc ctgctctgag 660tgcccaccca gctatggagg cagctgcagg aacaacttgt gttaccgagg taggaaattt 720actcccaaca cttttgcaat gaatttgccc tcagtctga759<210>24<211>1494<212>DNA<213>人(Homo sapiens)<400>24atgagctgcg tcctgggtgg tgtcatcccc ttggggctgc tgttcctggt ctgcggatcc 60caaggctacc tcctgcccaa cgtcactctc ttagaggagc tgctcagcaa ataccagcac 120aacgagtctc actcccgggt ccgcagagcc atccccaggg aggacaagga ggagatcctc 180atgctgcaca acaagcttcg gggccaggtg cagcctcagg cctccaacat ggagtacatg 240acctgggatg acgaactgga gaagtctgct gcagcgtggg ccagtcagtg catctgggag 300cacgggccca ccagtctgct ggtgtccatc gggcagaacc tgggcgctca ctggggcagg 360tatcgctctc cggggttcca tgtgcagtcc tggtatgacg aggtgaagga ctacacctac 420ccctacccga gcgagtgcaa cccctggtgt ccagagaggt gctcggggcc catgtgcacg 480cactacacac agatagtttg ggccaccacc aacaagatcg gttgtgctgt gaacacctgc 540cggaagatga ctgtctgggg agaagtttgg gagaacgcgg tctactttgt ctgcaattat 600tctccaaagg ggaactggat tggagaagcc ccctacaaga atggccggcc ctgctctgag 660tgcccaccca gctatggagg cagctgcagg aacaacttgt gttaccgaga agaaacctac 720actccaaaac ctgaaacgga cgagatgaat gaggtggaaa cggctcccat tcctgaagaa 780aaccatgttt ggctccaacc gagggtgatg agacccacca agcccaagaa aacctctgcg 840gtcaactaca tgacccaagt cgtcagatgt gacaccaaga tgaaggacag gtgcaaaggg 900tccacgtgta acaggtacca gtgcccagca ggctgcctga accacaaggc gaagatcttt 960ggaactctgt tctatgaaag ctcgtctagc atatgccgcg ccgccatcca ctacgggatc1020ctggatgaca agggaggcct ggtggatatc accaggaacg ggaaggtccc cttcttcgtg1080aagtctgaga gacacggcgt gcagtccctc agcaaataca aaccttccag ctcattcatg1140gtgtcaaaag tgaaagtgca ggatttggac tgctacacga ccgttgctca gctgtgcccg1200tttgaaaagc cagcaactca ctgcccaaga atccattgtc cggcacactg caaagacgaa1260ccttcctact gggctccggt gtttggaacc aacatctatg cagatacctc aagcatctgc1320aagacagccg tgcacgcggg agtcatcagc aacgagagtg ggggtgacgt ggacgtgatg1380cccgtggata aaaagaagac ctacgtgggc tcgctcagga atggagttca gtctgaaagc1440ctggggactc ctcgggatgg aaaggccttc cggatctttg ctgtcaggca gtga 1494<210>25<211>1315<212>DNA<213>人(Homo sapiens)<400>25batgctgcac aacaagcttc ggggccaggt gcagcctcag gcctccaaca tggagtacat 60gacctgggat gacgaactgg agaagtctgc tgcagcgtgg gccagtcagt gcatctggga 120gcacgggccc accagtctgc tggtgtccat cgggcagaac ctgggcgctc actggggcag 180gtatcgctct ccggggttcc atgtgcagtc ctggtatgac gaggtgaagg actacaccta 240cccctacccg agcgagtgca acccctggtg tccagagagg tgctcggggc ccatgtgcac 300gcactacaca cagatagttt gggccaccac caacaagatc ggttgtgctg tgaacacctg 360ccggaagatg actgtctggg gagaagtttg ggagaacgcg gtctactttg tctgcaatta 420ttctccaaag gggaactgga ttggagaagc cccctacaag aatggccggc cctgctctga 480gtgcccaccc agctatggag gcagctgcag gaacaacttg tgttaccgag aagaaaccta 540cactccaaaa cctgaaacgg acgagatgaa tgaggtggaa acggctccca ttcctgaaga 600aaaccatgtt tggctccaac cgagggtgat gagacccacc aagcccaaga aaacctctgc 660ggtcaactac atgacccaag tcgtcagatg tgacaccaag atgaaggaca ggtgcaaagg 720gtccacgtgt aacaggtacc agtgcccagc aggctgcctg aaccacaagg cgaagatctt 780tggaactctg ttctatgaaa gctcgtctag catatgccgc gccgccatcc actacgggat 840cctggatgac aagggaggcc tggtggatat caccaggaac gggaaggtcc ccttcttcgt 900gaagtctgag agacacggcg tgcagtccct cagcaaatac aaaccttcca gctcattcat 960ggtgtcaaaa gtgaaagtgc aggatttgga ctgctacacg accgttgctc agctgtgccc1020gtttgaaaag ccagcaactc actgcccaag aatccattgt ccggcacact gcaaagacga1080accttcctac tgggctccgg tgtttggaac caacatctat gcagatacct caagcatctg1140caagacagcc gtgcacgcgg gagtcatcag caacgagagt gggggtgacg tggacgtgat1200gcccgtggat aaaaagaaga cctacgtggg ctcgctcagg aatggagttc agtctgaaag1260cctggggact cctcgggatg gaaaggcctt ccggatcttt gctgtcaggc agtga 1315<210>26<211>927<212>DNA<213>人(Homo sapiens)<400>26atggttgggg gcgtcctcgc ctcgctgggc ttcgtcttct cggctttcgc cagcgatctg 60ctgcatctct acctcggcct gggcctcctc gctggctttg gttgggccct ggtgttcgcc 120cccgccctag gcaccctctc gcgttacttc tcccgccgtc gagtcttggc ggtggggctg 180gcgctcaccg gcaacggggc ctcctcgctg ctcctggcgc ccgccttgca gcttcttctc 240gatactttcg gctggcgggg cgctctgctc ctcctcggcg cgatcaccct ccacctcacc 300ccctgtggcg ccctgctgct acccctggtc cttcctggag accccccagc cccaccgcgt 360agtcccctag ctgccctcgg cctgagtctg ttcacacgcc gggccttctc aatctttgct 420ctaggcacag ccctggttgg gggcgggtac ttcgttcctt acgtgcactt ggctccccac 480gctttagacc ggggcctggg gggatacgga gcagcgctgg tggtggccgt ggctgcgatg 540ggggatgcgg gcgcccggct ggtctgcggg tggctggcag accaaggctg ggtgcccctc 600ccgcggctgc tggccgtatt cggggctctg actgggctgg ggctgtgggt ggtggggctg 660gtgcccgtgg tgggcggcga agagagctgg gggggtcccc tgctggccgc ggctgtggcc 720tatgggctga gcgcggggag ttacgccccg ctggttttcg gtgtactccc cgggctggtg 780ggcgtcggag gtgtggtgca ggccacaggg ctggtgatga tgctgatgag cctcgggggg 840ctcctgggcc ctcccctgtc aggtaaggac ctgagctcac agatctgcct acaactatcc 900tctgcccctg gggttcgagg cttctaa 927<210>27<211>1344<212>DNA<213>人(Homo sapiens)<400>27atgacccccc agcccgccgg acccccggat gggggctggg gctgggtggt ggcggccgca 60gccttcgcga taaacgggct gtcctacggg ctgctgcgct cgctgggcct tgccttccct 120gaccttgccg agcactttga ccgaagcgcc caggacactg cgtggatcag cgccctggcc 180ctggccgtgc agcaggcagc cagccccgtg ggcagcgccc tgagcacgcg ctggggggcc 240cgccccgtgg tgatggttgg gggcgtcctc gcctcgctgg gcttcgtctt ctcggctttc 300gccagcgatc tgctgcatct ctacctcggc ctgggcctcc tcgctggctt tggttgggcc 360ctggtgttcg cccccgccct aggcaccctc tcgcgttact tctcccgccg tcgagtcttg 420gcggtggggc tggcgctcac cggcaacggg gcctcctcgc tgctcctggc gcccgccttg 480cagcttcttc tcgatacttt cggctggcgg ggcgctctgc tcctcctcgg cgcgatcacc 540ctccacctca ccccctgtgg cgccctgctg ctacccctgg tccttcctgg agacccccca 600gccccaccgc gtagtcccct agctgccctc ggcctgagtc tgttcacacg ccgggccttc 660tcaatctttg ctctaggcac agccctggtt gggggcgggt acttcgttcc ttacgtgcac 720ttggctcccc acgctttaga ccggggcctg gggggatacg gagcagcgct ggtggtggcc 780gtggctgcga tgggggatgc gggcgcccgg ctggtctgcg ggtggctggc agaccaaggc 840tgggtgcccc tcccgcggct gctggccgta ttcggggctc tgactgggct ggggctgtgg 900gtggtggggc tggtgcccgt ggtgggcggc gaagagagct gggggggtcc cctgctggcc 960gcggctgtgg cctatgggct gagcgcgggg agttacgccc cgctggtttt cggtgtactc1020cccgggctgg tgggcgtcgg aggtgtggtg caggccacag ggctggtgat gatgctgatg1080agcctcgggg ggctcctggg ccctcccctg tcaggcttcc taagggatga gacaggagac1140ttcaccgcct ctttcctcct gtctggttct ttgatcctct ccggcagctt catctacata1200gggttgccca gggcgctgcc ctcctgtggt ccagcctccc ctccagccac gcctccccca1260gagacggggg agctgcttcc cgctccccag gcagtcttgc tgtccccagg aggccctggc1320tccactctgg acaccacttg ttga 1344<210>28<211>1375<212>DNA<213>人(Homo sapiens)<400>28batggcgcgc aggacagagc cccccgacgg gggctgggga tgggtggtgg tgctctcagc 60gttcttccag tcggcgcttg tgtttggggt gctccgctcc tttggggtct tcttcgtgga 120gtttgtggcg gcgtttgagg agcaggcagc gcgcgtctcc tggatcgcct ccataggaat 180cgcggtgcag cagtttggga gcccggtagg cagtgccctg agcacgaagt tcgggcccag 240gcccgtggtg atgactggag gcatcttggc tgcgctgggg atgctgctcg cctcttttgc 300tacttccttg acccacctat acctgagtat tgggttgctg tcaggctctg gctgggcttt 360gaccttcgct ccgaccctgg cctgcctgtc ctgttatttc tctcgccgac gatccctggc 420caccgggctg gcactgacag gcgtgggcct ctcctccttc acatttgccc cctttttcca 480gtggctgctc agccactacg cctggagggg gtccctgctg ctggtgtctg ccctctccct 540ccacctagtg gcctgtggtg ctctcctccg cccaccctcc ctggctgagg accctgctgt 600gggtggtccc agggcccaac tcacctctct cctccatcat ggccccttcc tccgttacac 660tgttgccctc accctgatca acactggcta cttcattccc tacctccacc tggtggccca 720tctccaggac ctggattggg acccactacc tgctgccttc ctactctcag ttgttgctat 780ttctgacctc gtggggcgtg tggtctccgg atggctggga gatgcagtcc cagggcctgt 840gacacgactc ctgatgctct ggaccacctt gactggggtg tcactagccc tgttccctgt 900agctcaggct cccacagccc tggtggctct ggctgtggcc tacggcttca catcaggggc 960tctggcccca ctggccttct ccgtgctgcc tgaactaata gggactagaa ggatttactg1020tggcctggga ctgttgcaga tgatagagag catcgggggg ctgctggggc ctcctctctc1080aggctacctc cgggatgtgt caggcaacta cacggcttct tttgtggtgg ctggggcctt1140ccttctttca gggagtggca ttctcctcac cctgccccac ttcttctgct tctcaactac1200tacctccggg cctcaggacc ttgtaacaga agcactagat actaaagttc ccctacccaa1260ggaggggctg gaaggaggac tgaactccac agagtcaggc ccagaaagcc aaagcttgac1320agctccaggt cttctcttgc cacgtcttgg tctccacaga accacagtgc cttaa 1375<210>29<211>510<212>DNA<213>人(Homo sapiens)<400>29atgaccatga agacctctgg ggccacttgt gatgcaaaca gtgtgatgaa ctgcgggatc 60cgcgggtctg aaatgtttgc tgagatggat ttgagggcca taaaacctta ccagactctg 120atcaaaaaag tcgggcagag acattgcgtg gaccctgctg tcatcgcagc catcatctcc 180agggaaagcc atgggggatc tgtcctgcaa gacggctggg accacagggg acttaaattt 240ggcttgatgc agcttgataa acaaacgtac caccctgtcg gtgcctggga tagcaaagag 300cacctttcac aggctactgg gattctaaca gagagaatta aggcaatcca gaaaaaattc 360cccacgtgga gtgttgctca gcacctcaaa ggtggtctct cagcttttaa gtcaggaatt 420gaagcgattg ccaccccatc ggacatagac aatgacttcg tcaatgatat cattgctcga 480gctaagttct ataaaagaca aagcttctag 510<210>30<211>561<212>DNA<213>人(Homo sapiens)<400>30atgaagcctc acctacatcc acgcctgtac cacggctgct atggggacat catgaccatg 60aagacctctg gggccacttg tgatgcaaac agtgtgatga actgcgggat ccgcgggtct 120gaaatgtttg ctgagatgga tttgagggcc ataaaacctt accagactct gatcaaaaaa 180gtcgggcaga gacattgcgt ggaccctgct gtcatcgcag ccatcatctc cagggaaagc 240catgggggat ctgtcctgca agacggctgg gaccacaggg gacttaaatt tggcttgatg 300cagcttgata aacaaacgta ccaccctgtc ggtgcctggg atagcaaaga gcacctttca 360caggctactg ggattctaac agagagaatt aaggcaatcc agaaaaaatt ccccacgtgg 420agtgttgctc agcacctcaa aggtggtctc tcagctttta agtcaggaat tgaagcgatt 480gccaccccat cggacataga caatgacttc gtcaatgata tcattgctcg agctaagttc 540tataaaagac aaagcttcta g 561<210>31<211>2028<212>DNA<213>人(Homo sapiens)<400>31atggagagcg gcaccagcag ccctcagcct ccacagttag atcccctgga tgcgtttccc 60cagaagggct tggagcctgg ggacatcgcg gtgctagttc tgtacttcct ctttgtcctg 120gctgttggac tatggtccac agtgaagacc aaaagagaca cagtgaaagg ctacttcctg 180gctggagggg acatggtgtg gtggccagtg ggtgcatcct tgtttgccag caatgttgga 240agtggacatt tcattggcct ggcagggtca ggtgctgcta cgggcatttc tgtatcagct 300tatgaactta atggcttgtt ttctgtgctg atgttggcct ggatcttcct acccatctac 360attgctggtc aggtcaccac gatgccagaa tacctacgga agcgcttcgg tggcatcaga 420atccccatca tcctggctgt actctaccta tttatctaca tcttcaccaa gatctcggta 480gacatgtatg caggtgccat cttcatccag cagtctttgc acctggatct gtacctggcc 540atagttgggc tactggccat cactgctgta tacacggttg ctggtggcct ggctgctgtg 600atctacacgg atgccctgca gacgctgatc atgcttatag gagcgctcac cttgatgggc 660tacagtttcg ccgcggttgg tgggatggaa ggactgaagg agaagtactt cttggccctg 720gctagcaacc ggagtgagaa cagcagctgc gggctgcccc gggaagatgc cttccatatt 780ttccgagatc cgctgacatc tgatctcccg tggccggggg tcctatttgg aatgtccatc 840ccatccctct ggtactggtg cacggatcag gtgattgtcc agcggactct ggctgccaag 900aacctgtccc atgccaaagg aggtgctctg atggctgcat acctgaaggt gctgcccctc 960ttcataatgg tgttccctgg gatggtcagc cgcatcctct tcccagatca agtggcctgt1020gcagatccag agatctgcca gaagatctgc agcaacccct caggctgttc ggacatcgcg1080tatcccaaac tcgtgctgga actcctgccc acagggctcc gtgggctgat gatggctgtg1140atggtggcgg ctctcatgtc ctccctcacc tccatcttta acagtgccag caccatcttc1200accatggacc tctggaatca cctccggcct cgggcatctg agaaggagct catgattgtg1260ggcagggtgt ttgtgctgct gctggtcctg gtctccatcc tctggatccc tgtggtccag1320gccagccagg gcggccagct cttcatctat atccagtcca tcagctccta cctgcagccg1380cctgtggcgg tggtcttcat catgggatgt ttctggaaga ggaccaatga aaagggtgcc1440ttctggggcc tgatctcggg cctgctcctg ggcttggtta ggctggtcct ggactttatt1500tacgtgcagc ctcgatgcga ccagccagat gagcgcccgg tcctggtgaa gagcattcac1560tacctctact tctccatgat cctgtccacg gtcaccctca tcactgtctc caccgtgagc1620tggttcacag agccaccctc caaggagatg gtcagccacc tgacctggtt tactcgtcac1680gaccccgtgg tccagaagga acaagcacca ccagcagctc ccttgtctct taccctctct1740cagaacggga tgccagaggc cagcagcagc agcagcgtcc agttcgagat ggttcaagaa1800aacacgtcta aaacccacag ctgtgacatg accccaaagc agtccaaagt ggtgaaggcc1860atcctgtggc tctgtggaat acaggagaag ggcaaggaag agctcccggc cagagcagaa1920gccatcatag tttccctgga agaaaacccc ttggtgaaga ccctcctgga cgtcaacctc1980attttctgcg tgagctgcgc catctttatc tggggctatt ttgcttag 2028<210>32<211>1458<212>DNA<213>人(Homo sapiens)<400>32atggagccct gttggggaga aggcttgttt catctagcac ccccacgcca ccatccccag 60aaggctgact ggcatttctg tccacagcac attcaggaat tcaccaatga gacatggcag 120gcgcgtactg gagagccact gcccgatcac ctagtcctgc ttatgtggtc cctcatcgtg 180tctctgtatc ccctgggagg cctctttgga gcactgcttg caggtccctt ggccatcacg 240ctgggaagga agaagtccct cctggtgaat aacatctttg tggtgtcagc agcaatcctg 300tttggattca gccgcaaagc aggctccttt gagatgatca tgctgggaag actgctcgtg 360ggagtcaatg caggtgtgag catgaacatc cagcccatgt acctggggga gagcgcccct 420aaggagctcc gaggagctgt ggccatgagc tcagccatct ttacggctct ggggatcgtg 480atgggacagg tggtcggact cagggagctc ctaggtggcc ctcaggcctg gcccctgctg 540ctggccagct gcctggtgcc cggggcgctc cagctcgcct ccctgcctct gctccctgaa 600agcccgcgct acctcctcat tgactgtgga gacaccgagg cctgcctggc agcactacgg 660cggctccggg gctccgggga cttggcaggg gagctggagg agctggagga ggagcgcgct 720gcctgccagg gctgccgtgc ccggcgccca tgggagctgt tccagcatcg ggccctgagg 780agacaggtga caagcctcgt ggttctgggc agtgccatgg agctctgcgg gaatgactcg 840gtgtacgcct acgcctcctc cgtgttccgg aaggcaggag tgccggaagc gaagatccag 900tacgcgatca tcgggactgg gagctgcgag ctgctcacgg cggttgttag ttgtgtggta 960atcgagaggg tgggtcggcg cgtgctgctc atcggtgggt acagcctgat gacctgctgg1020gggagcatct tcactgtggc cctgtgcctg cagagctcct tcccctggac actctacctg1080gccatggcct gcatctttgc cttcatcctc agctttggca ttggccctgc cggagtgacg1140gggatcctgg ccacagagct gtttgaccag atggccaggc ctgctgcctg catggtctgc1200ggggcgctca tgtggatcat gctcatcctg gtcggcctgg gatttccctt tatcatggag1260gccttgtccc acttcctcta tgtccctttc cttggtgtct gtgtctgtgg ggccatctac1320actggcctgt tccttcctga gaccaaaggc aagaccttcc aagagatctc caaggaatta1380cacagactca acttccccag gcgggcccag ggccccacgt ggaggagcct ggaggttatc1440cagtcaacag aactctag 1458<210>33<211>1491<212>DNA<213>人(Homo sapiens)<400>33atgagagcgc tccgaagact gattcagggc aggatcctgc tcctgaccat ctgcgctgcc 60ggcattggtg ggacttttca gtttggctat aacctctcta tcatcaatgc cccgaccttg 120cacattcagg aattcaccaa tgagacatgg caggcgcgta ctggagagcc actgcccgat 180cacctagtcc tgcttatgtg gtccctcatc gtgtctctgt atcccctggg aggcctcttt 240ggagcactgc ttgcaggtcc cttggccatc acgctgggaa ggaagaagtc cctcctggtg 300aataacatct ttgtggtgtc agcagcaatc ctgtttggat tcagccgcaa agcaggctcc 360tttgagatga tcatgctggg aagactgctc gtgggagtca atgcaggtgt gagcatgaac 420atccagccca tgtacctggg ggagagcgcc cctaaggagc tccgaggagc tgtggccatg 480agctcagcca tctttacggc tctggggatc gtgatgggac aggtggtcgg actcagggag 540ctcctaggtg gccctcaggc ctggcccctg ctgctggcca gctgcctggt gcccggggcg 600ctccagctcg cctccctgcc tctgctccct gaaagcccgc gctacctcct cattgactgt 660ggagacaccg aggcctgcct ggcagcacta cggcggctcc ggggctccgg ggacttggca 720ggggagctgg aggagctgga ggaggagcgc gctgcctgcc agggctgccg tgcccggcgc 780ccatgggagc tgttccagca tcgggccctg aggagacagg tgacaagcct cgtggttctg 840ggcagtgcca tggagctctg cgggaatgac tcggtgtacg cctacgcctc ctccgtgttc 900cggaaggcag gagtgccgga agcgaagatc cagtacgcga tcatcgggac tgggagctgc 960gagctgctca cggcggttgt tagttgtgtg gtaatcgaga gggtgggtcg gcgcgtgctg1020ctcatcggtg ggtacagcct gatgacctgc tgggggagca tcttcactgt ggccctgtgc1080ctgcagagct ccttcccctg gacactctac ctggccatgg cctgcatctt tgccttcatc1140ctcagctttg gcattggccc tgccggagtg acggggatcc tggccacaga gctgtttgac1200cagatggcca ggcctgctgc ctgcatggtc tgcggggcgc tcatgtggat catgctcatc1260ctggtcggcc tgggatttcc ctttatcatg gaggccttgt cccacttcct ctatgtccct1320ttccttggtg tctgtgtctg tggggccatc tacactggcc tgttccttcc tgagaccaaa1380ggcaagacct tccaagagat ctccaaggaa ttacacagac tcaacttccc caggcgggcc1440cagggcccca cgtggaggag cctggaggtt atccagtcaa cagaactcta g 1491<210>34<211>1501<212>DNA<213>人(Homo sapiens)<400>34batgctccac gccctcctgc gatctagaat gattcagggc aggatcctgc tcctgaccat 60ctgcgctgcc ggcattggtg ggacttttca gtttggctat aacctctcta tcatcaatgc 120cccgaccttg cacattcagg aattcaccaa tgagacatgg caggcgcgta ctggagagcc 180actgcccgat cacctagtcc tgcttatgtg gtccctcatc gtgtctctgt atcccctggg 240aggcctcttt ggagcactgc ttgcaggtcc cttggccatc acgctgggaa ggaagaagtc 300cctcctggtg aataacatct ttgtggtgtc agcagcaatc ctgtttggat tcagccgcaa 360agcaggctcc tttgagatga tcatgctggg aagactgctc gtgggagtca atgcaggtgt 420gagcatgaac atccagccca tgtacctggg ggagagcgcc cctaaggagc tccgaggagc 480tgtggccatg agctcagcca tctttacggc tctggggatc gtgatgggac aggtggtcgg 540actcagggag ctcctaggtg gccctcaggc ctggcccctg ctgctggcca gctgcctggt 600gcccggggcg ctccagctcg cctccctgcc tctgctccct gaaagcccgc gctacctcct 660cattgactgt ggagacaccg aggcctgcct ggcagcacta cggcggctcc ggggctccgg 720ggacttggca ggggagctgg aggagctgga ggaggagcgc gctgcctgcc agggctgccg 780tgcccggcgc ccatgggagc tgttccagca tcgggccctg aggagacagg tgacaagcct 840cgtggttctg ggcagtgcca tggagctctg cgggaatgac tcggtgtacg cctacgcctc 900ctccgtgttc cggaaggcag gagtgccgga agcgaagatc cagtacgcga tcatcgggac 960tgggagctgc gagctgctca cggcggttgt tagttgtgtg gtaatcgaga gggtgggtcg1020gcgcgtgctg ctcatcggtg ggtacagcct gatgacctgc tgggggagca tcttcactgt1080ggccctgtgc ctgcagagct ccttcccctg gacactctac ctggccatgg cctgcatctt1140tgccttcatc ctcagctttg gcattggccc tgccggagtg acggggatcc tggccacaga1200gctgtttgac cagatggcca ggcctgctgc ctgcatggtc tgcggggcgc tcatgtggat1260catgctcatc ctggtcggcc tgggatttcc ctttatcatg gaggccttgt cccacttcct1320ctatgtccct ttccttggtg tctgtgtctg tggggccatc tacactggcc tgttccttcc1380tgagaccaaa ggcaagacct tccaagagat ctccaaggaa ttacacagac tcaacttccc1440caggcgggcc cagggcccca cgtggaggag cctggaggtt atccagtcaa cagaactcta1500g1501<210>35<211>4077<212>DNA<213>人(Homo sapiens)<400>35atggtagtgg tgaagcccat gaacacaatg gctccggtgg tcacccggaa taccggtctt 60attctctatg agggtcagtc tcggcccctc acaggccctg caggcagtgg tccgcaaaac 120ttggtcatca gcgatgagga tgacctagaa gcagtgcggc tagaggtggt ggctgggctc 180cggcatggtc accttgtcat tctgggtgct tccagtggca gctctgctcc caagagcttt 240acagtggctg agctggcagc cggccaggtg gtctaccagc atgatgacag agacggctcg 300ctgagcgaca acctggtgct tcgcatggtg gatggaggag gcaggcacca ggtacagttt 360ctgttcccca tcaccttagt gcctgtggat gaccagccac ctgttctcaa tgccaacacg 420gggctgacac tggcagaggg tgaaacagtg cccatcctgc ccctttccct gagtgcaact 480gacatggatt cagatgattc tctgctgctt tttgtgctgg agtcaccctt cttaactacg 540gggcatctgc ttctccgcca aactcaccct ccccatgaga agcaggaact tctcagaggc 600ctttggagga aggagggggc attttatgag cgaacagtga cagagtggca gcagcaggac 660ataacagagg gcaggctgtt ctatagacac tctgggcccc atagtcctgg gccagtcaca 720gaccagttca catttagagt ccaggataac catgaccctc ctaatcagtc cgggctacag 780cggtttgtga ttcgtatcca tcctgtggat cgcctccctc cggagctggg cagtggctgt 840ccccttcgta tggtggtaca ggaatcccag ctcacaccac tgaggaagaa gtggctgcgc 900tacactgacc tggacacaga tgaccgagaa ctacgttaca cagtgactca gtcccccaca 960gacacagacg aaaatcacct gccagcccca ctgggtacct tggtcttgac tgacaacccc1020tcagtcgtgg tgacccattt tacccaagcc cagatcaacc atcataaaat tgcttacaga1080cccccgggtc aagaactggg cgtggctact cgagtggccc agttccagtt ccaggtggaa1140gaccgagctg ggaatgtggc tccaggtacc tttacccttt acttgcatcc cgtggacaac1200cagccacctg agatcctcaa caccggcttc actattcagg agaagggtca ccacatcctg1260agtgagacag agttgcacgt gaatgatgta gacactgatg ttgcccatat ctctttcact1320ctcactcagg cacccaaaca tggccacatg agagtgtctg gacagatcct gcatgtaggg1380ggtctcttcc acttggagga cataaaacag ggccgagttt cctatgccca taatggggac1440aagtccctga ctgatagctg ctccttggaa gtcagtgaca gacatcatgt ggtgcccatc1500actctcagag taaatgtccg gccagtggat gatgaagtgc ccatactgag ccatcctact1560ggcactctgg agtcctatct agatgtctta gaaaatgggg ctactgaaat cactgccaat1620gttattaagg ggaccaatga ggaaactgat gacttgatgt tgactttcct cttggaagat1680ccacctttgt atggggaaat cttggtcaat ggcattccag cagagcagtt tactcaaagg1740gacatcttgg agggctctgt tgtatatacc cacaccagtg gtgagatagg cctattgcct1800aaagcggatt cttttaacct gagtctgtca gatatgtctc aagaatggag aattggtggc1860aatactatcc aaggagttac tatatgggtg accatcctgc ctgttgatag ccaggcccca1920gaaatctttg taggtgaaca gttgatagta atggaaggtg ataaaagtgt tataacatca1980gtgcatataa gtgctgaaga tgtcgactcc ctgaatgatg acatcttgtg cactatagtt2040attcagccta cttcaggtta tgttgaaaac atttctccag caccaggctc tgagaaatca2100agagcaggga ttgccataag tgctttcaac ttgaaagatc tcaggcaggg ccacataaac2160tatgtccaga gtgtccataa aggggtggaa cctgtggagg accgatttgt atttcgttgt2220tctgatggca ttaacttttc agagagacag ttcttcccca ttgtaatcat tcccaccaat2280gatgaacagc cagagatgtt tatgagagaa tttatggtga tggaaggcat gagtctggta2340attgatacac ccattctcaa tgctgctgat gctgatgttc ccctggatga tttaactttc2400actattaccc aattccccac tcatggtcac atcatgaatc agctgataaa tggcacggtt2460ttggtcgaaa gcttcacctt ggatcagatc atagagagtt ccagcattat ttatgagcat2520gatgactccg agacccagga agacagtttt gtgattaaac taacagatgg gaagcactct2580gtggaaaaga cggtcctcat tatagttatc cctgttgatg atgagacgcc cagaatgact2640atcaataatg gactagaaat agaaattggg gataccaaga ttatcaacaa caaaatatta2700atggcaacag atttagattc agaagacaaa tctttggttt atattattcg ttatgggcca2760ggacatggct tattacagag acgaaaacct actggtgcct ttgaaaatat cacactgggc2820atgaatttta cccaggatga agtagacaga aacttaattc agtatgtcca tttggggcaa2880gagggcattc gggacctaat taaatttgat gtgactgatg gaataaatcc cctcatagat2940cgttactttt atgtgtccat cgggagcatt gacattgtct tccctgatgt gataagtaag3000ggagtgtcct tgaaagaagg tggcaaagtc actcttacaa cagacctact aagcactagt3060gacttgaaca gtcctgatga aaacttggtt tttaccatca ccagggctcc catgcgaggt3120cacctggaat gcacggatca gcctggtgtg tccatcacgt ctttcactca gctgcaactg3180gctggaaaca aaatctacta catccacaca gctgatgatg aagtgaaaat ggacagtttt3240gagtttcaag tcaccgatgg acgtaaccct gtctttcgga cattccgtat ctccattagc3300gatgtggaca ataaaaagcc agtggtcacc atccacaagc tggttgtcag tgaaagtgaa3360aacaagctga ttactccttt tgagctcact gtcgaagaca gagatactcc tgacaagctc3420ctgaaattca ctatcaccca ggtgcctatt catggccatc tcctattcaa caataccaga3480cctgtcatgg tttttaccaa gcaagacttg aatgaaaact taatcagcta caaacatgat3540ggcactgagt caagtgaaga tagcttctcc ttcacagtga ctgatggcac ccatacagac3600ttctatgttt ttcctgatac ggtgtttgaa acaaggagac cccaagtgat gaagatccag3660gtcttggctg ttgacaacag tgtcccccaa atcgcagtga ataagggggc ctctacactt3720cgcactctag ccactggcca cttggggttc atgatcacaa gcaaaatatt gaaagtggag3780gacagagaca gcttacacat ttctcttaga tttatcgtga cagaggcccc tcaacatgga3840tatcttctca acctggacaa aggcaaccac agcatcactc agttcacaca agctgacatt3900gatgacatga aaatatgcta tgtcttaaga gaaggggcta atgccacaag tgatatgttc3960tattttgcag ttgaagatgg tggtaagtat tcccctctcc tggtagtgac cgcaaggaga4020gacgcttttc ttggttgctc tctgatgaca ttattacaag aagtcttcat caagtaa 4077<210>36<211>9318<212>DNA<213>人(Homo sapiens)<400>36atggcacgat cttggctcac tgcaacctcc acctcccggc ccgctgcctt cggcagggcg 60ttgctgtccc ctggtctcgc gggggctgca ggggtccctg ctgaggaggc catagtgctg 120gcgaaccgcg gactccgggt gcctttcggc cgtgaagtct ggctggatcc cctgcatgac 180ctggtgttgc aggtgcagcc cggggaccgc tgcgcggttt cggtactaga caacgacgca 240ctggcccagc gaccgggccg cctgagtccc aagcgcttcc cgtgcgactt tggccctggc 300gaggtgcgct actctcacct gggcgcgcgc agcccgtctc gggaccgcgt ccggctgcag 360ctgcgctatg acgcgcccgg aggggcagta gtgctaccac tggtactgga ggtggaggtg 420gtcttcaccc agctggaggt tgtgactcgg aacttgcctc tggtcgtgga agaactgctg 480gggaccagca atgccctgga cgcgcggagc ctggagttcg ccttccagcc cgagacagag 540gagtgccgcg tgggcatcct gtccggcttg ggcgcgctgc ctcgctatgg agaactcctc 600cactacccgc aggtccctgg aggagccaga gagggaggcg ccccggagac tctcctgatg 660gactgcaaag ctttccagga actaggcgtg cgctatcgcc acacagccgc cagtcgctca 720ccaaacaggg actggatacc catggtggtg gagctgcgtt cacgaggggc tcctgtgggc 780agccctgctt tgaaacgcga gcacttccag gttctggtga ggatccgagg aggggccgag 840aacactgcac ccaagcccag tttcgtggcc atgatgatga tggaggtgga ccagtttgta 900ctgacggccc tgaccccaga catgctggca gccgaggatg ctgagtctcc ctctgacctg 960ttgatcttca accttacttc tccattccag cctggccagg gctacttggt gagcaccgat1020gatcgcagcc tgcccctttc ctccttcact cagagggatc tgcggctcct gaagattgcc1080taccagcccc cttctgaaga ctctgaccag gagcgcctct ttgaactgga attggaggta1140gtggatctag aaggagcagc ttcagaccct tttgccttca tggtagtggt gaagcccatg1200aacacaatgg ctccggtggt cacccggaat accggtctta ttctctatga gggtcagtct1260cggcccctca caggccctgc aggcagtggt ccgcaaaact tggtcatcag cgatgaggat1320gacctagaag cagtgcggct agaggtggtg gctgggctcc ggcatggtca ccttgtcatt1380ctgggtgctt ccagtggcag ctctgctccc aagagcttta cagtggctga gctggcagcc1440ggccaggtgg tctaccagca tgatgacaga gacggctcgc tgagcgacaa cctggtgctt1500cgcatggtgg atggaggagg caggcaccag gtacagtttc tgttccccat caccttagtg1560cctgtggatg accagccacc tgttctcaat gccaacacgg ggctgacact ggcagagggt1620gaaacagtgc ccatcctgcc cctttccctg agtgcaactg acatggattc agatgattct1680ctgctgcttt ttgtgctgga gtcacccttc ttaactacgg ggcatctgct tctccgccaa1740actcaccctc cccatgagaa gcaggaactt ctcagaggcc tttggaggaa ggagggggca1800ttttatgagc gaacagtgac agagtggcag cagcaggaca taacagaggg caggctgttc1860tatagacact ctgggcccca tagtcctggg ccagtcacag accagttcac atttagagtc1920caggataacc atgaccctcc taatcagtcc gggctacagc ggtttgtgat tcgtatccat1980cctgtggatc gcctccctcc ggagctgggc agtggctgtc cccttcgtat ggtggtacag2040gaatcccagc tcacaccact gaggaagaag tggctgcgct acactgacct ggacacagat2100gaccgagaac tacgttacac agtgactcag ccccccacag acacagacga aaatcacctg2160ccagccccac tgggtacctt ggtcttgact gacaacccct cagtcgtggt gacccatttt2220acccaagccc agatcaacca tcataaaatt gcttacagac ccccgggtca agaactgggc2280gtggctactc gagtggccca gttccagttc caggtggaag accgagctgg gaatgtggct2340ccaggtacct ttacccttta cttgcatccc gtggacaacc agccacctga gatcctcaac2400accggcttca ctattcagga gaagggtcac cacatcctga gtgagacaga gttgcacgtg2460aatgatgtag acactgatgt tgcccatatc tctttcactc tcactcaggc acccaaacat2520ggccacatga gagtgtctgg acagatcctg catgtagggg gtctcttcca cttggaggac2580ataaaacagg gccgagtttc ctatgcccat aatggggaca agtccctgac tgatagctgc2640tccttggaag tcagtgacag acatcatgtg gtgcccatca ctctcagagt aaatgtccgg2700ccagtggatg atgaagtgcc catactgagc catcctactg gcactctgga gtcctatcta2760gatgtcttag aaaatggggc tactgaaatc actgccaatg ttattaaggg gaccaatgag2820gaaactgatg acttgatgtt gactttcctc ttggaagatc cacctttgta tggggaaatc2880ttggtcaatg gcattccagc agagcagttt actcaaaggg acatcttgga gggctctgtt2940gtatataccc acaccagtgg tgagataggc ctattgccta aagcggattc ttttaacctg3000agtctgtcag ataagtctca agaatggaga attggtggca atactatcca aggagttact3060atatgggtga ccatcctgcc tgttgatagc caggccccag aaatctctgt aggtgaacag3120ttgatagtaa tggaaggtga taaaagtgtt ataacatcag tgcatataag tgctgaagat3180gtcgactccc tgaatgatga catcttgtgc actatagtta ttcagcctac ttcaggttat3240gttgaaaaca tttctccagc accaggctct gagaaatcaa gagcagggat tgccataagt3300gctttcaact tgaaagatct caggcagggc cacataaact atgtccagag tgtccataaa3360ggggtggaac ctgtggagga ccgatttgta tttcgttgtt ctgatggcat taacttttca3420gagagacagt tcttccccat tgtaatcatt cccaccaatg atgaacagcc agagatgttt3480atgagagaat ttatggtgat ggaaggcatg agtctggtaa ttgatacacc cattctcaat3540gctgctgatg ctgatgttcc cctggatgat ttaactttca ctattaccca attccccact3600catggtcaca tcatgaatca gctgataaat ggcacggttt tggtcgaaag cttcaccttg3660gatcagatca tagagagttc cagcattatt tatgagcatg atgactccga gacccaggaa3720gacagttttg tgattaaact aacagatggg aagcactctg tggaaaagac ggtcctcatt3780atagttatcc ctgttgatga tgagacgccc agaatgacta tcaataatgg actagaaata3840gaaattgggg ataccaagat tatcaacaac aaaatattaa tggcaacaga tttagattca3900gaagacaaat ctttggttta tattattcgt tatgggccag gacatggctt attacagaga3960cgaaaaccta ctggtgcctt tgaaaatatc acactgggca tgaattttac ccaggatgaa4020gtagacagaa acttaattca gtatgtccat ttggggcaag agggcattcg ggacctaatt4080aaatttgatg tgactgatgg aataaatccc ctcatagatc gttactttta tgtgtccatc4140gggagcattg acattgtctt ccctgatgtg ataagtaagg gagtgtcctt gaaagaaggt4200ggcaaagtca ctcttacaac agacctacta agcactagtg acttgaacag tcctgatgaa4260aacttggttt ttaccatcac cagggctccc atgcgaggtc acctggaatg cacggatcag4320cctggtgtgt ccatcacgtc tttcactcag ctgcaactgg ctggaaacaa aatctactac4380atccacacag ctgatgatga agtgaaaatg gacagttttg agtttcaagt caccgatgga4440cgtaaccctg tctttcggac attccgtatc tccattagcg atgtggacaa taaaaagcca4500gtggtcacca tccacaagct ggttgtcagt gaaagtgaaa acaagctgat tactcctttt4560gagctcactg tcgaagacag agatactcct gacaagctcc tgaaattcac tatcacccag4620gtgcctattc atggccatct cctattcaac aataccagac ctgtcatggt ttttaccaag4680caagacttga atgaaaactt aatcagctac aaacatgatg gcactgagtc aagtgaagat4740agcttctcct tcacagtgac tgatggcacc catacagact tctatgtttt tcctgatacg4800gtgtttgaaa caaggagacc ccaagtgatg aagatccagg tcttggctgt tgacaacagt4860gtcccccaaa tcgcagtgaa taagggggcc tctacacttc gcactctagc cactggccac4920ttggggttca tgatcacaag caaaatattg aaagtggagg acagagacag cttacacatt4980tctcttagat ttatcgtgac agaggcccct caacatggat atcttctcaa cctggacaaa5040ggcaaccaca gcatcactca gttcacacaa gctgacattg atgacatgaa aatatgctat5100gtcttaagag aaggggctaa tgccacaagt gatatgttct attttgcagt tgaagatggt5160ggtggaaaca agttaacgta ccagaatttt cgtctgaatt gggcatggat ctcctttgaa5220aaggaatatt acctggtcaa tgaggactcc aaatttctag atgttgttct taaacgtaga5280ggttacttgg gagaaacttc ttttataagt attggcacaa gagacagaac tgcagaaaaa5340gacaaagact tcaagggcaa agcacagaaa caagtgcagt tcaacccagg ccagaccagg5400gccacatggc gagtgcggat cctgagtgat ggggagcatg agcagtctga aacctttcag5460gtggtactct cagagcccgt gctggctgcc ttggaattcc ccacagtcgc cactgttgag5520atcgttgatc caggagatga gccaactgtg tttattcccc agtccaaata ctccgttgaa5580gaagatgttg gtgagctgtt cattcccatc aggaggagcg gagatgtgag ccaggagttg5640atggtggtct gttataccca acaaggaaca gcaactggaa ctgtgccgac ttccgtgttg5700tcttactctg attacatatc caggcctgag gaccacacca gtgttgtccg ctttgacaaa5760gatgaacggg agaaactgtg tcggatagtc ataattgatg actctttgta cgaggaggag5820gaaaccttcc atgtccttct gagcatgccc atggggggaa gaatcggatc agagttccca5880ggggctcaag ttacaatcgt tcctgacaaa gatgatggtc catctgattc caaatttaat5940gttgctgaga actacagttt actgcctttc acctgttttc aaggtagcat agccacggca6000gaggcagcca cccagggagg gggacgcagc accagacaag tagctgcagt caaaaaagac6060aaagacttca agggcaaagc acagaaacaa gtgcagttca acccaggcca gaccagggcc6120acatggcgag tgcggatcct gagtgatggg gagcatgagc agtctgaaac ctttcaggtg6180gtactctcag agcccgtgct ggctgccttg gaattcccca cagtcgccac tgttgagatc6240gttgatccag gagatgcatg cccatggggg gaagaatcgg atcagagttc ccaggggctc6300aagttacaat cgttcctgac aaagatgatg gtgagtacta atttacttga aaattctttt6360tcccgggaag atcaacatca ggaacaactt tctagacaga aaaaatggga atctaaaaca6420atgataatat acacatttat tttatgtgag acagaaaagc cctgcattct tgagctgatg6480gacgatgtgc tctatgagga ggtagaggag ctccgcctgg tactcggcac tccacaaagc6540aactctccct ttggggctgc agttggtgaa caaaatgaaa ctctcataag gatccgagat6600gatgctgata agactgttat taaatttgga gaaaccaaat ttagtgtcac tgaacccaaa6660gaacctggag agtcggtggt tataagaatt ccagtgattc gccaaggaga cacttcaaag6720gtttccattg tgagagtcca caccaaggat ggctcggcca cctctggaga agactaccac6780cctgtgtcag aagaaattga gtttaaggaa ggggaaaccc agcacgtggt tgaaatcgaa6840gttacctttg acggggtgag agagatgaga gaggccttca ctgttcacct aaaacctgat6900gaaaatatga tagcagagat gcagctttcc aactttgagc tcaccctcag ccctgatggc6960acaagagttg gaaaccacaa gtgctccaac ctcctggatt atactgaagt gaagactcat7020tatggtttct tgactgatgc taccaaaaat ccagaaataa ttggagagac atatccttac7080cagtacagct tgtccatcag aggttccact accttgcgct tctaccggaa cctgaaccta7140gaggcctgtt tatgggagtt cgttagctac tatgacatgt cagaactcct tgctgactgc7200agatcagtgt tgaatgcaag catatttcat gagatggcac ctgaaggaaa gcaaagtaaa7260tgcttggtaa attctacttt atactctatt ttggaatgtc atgagagcct tccaaacttt7320tgcatttcag cattaaggat gggaaaatgg agaaaaataa aaagcaaacc atcagcacag7380actccatgtg ctcagaggct tcgtggtttt attgaccacc ccaggaaaca gcccctgcag7440caagccagtg ctgacccagg catgctcccc gtgatctcca ctagagagct ttccaacttt7500gagctcaccc tcagccctga tggcacaaga gttggaaacc acaagtgctc caacctcctg7560gattatactg aagtgaagac tcattatggt ttcttgactg atgctaccaa aaatccagaa7620ataattggag agacatatcc ttaccagtac agcttgtcca tcagaggttc cactaccttg7680cgcttctacc ggaacctgaa cctagaggcc tgtttatggg agttcgttag ctactatgac7740atgtcagaac tccttgctga ctgtggtggc accattggaa cagatggaca ggtcctaaac7800ctagtgcagt cctatgtgac ccttcgagtc cctctgtatg tttcctacgt gttccattcc7860cccgtggggg taggaggctg gcagcatttt gacttgaagt cagagcttcg tctaactttt7920gtgtacgaca ccgccatctt gtggaatgat ggaattggca gccccccaga ggctgaactt7980caaggttctc tctatccaac cagcatgcgc atcggtgatg aggggcgctt ggccgtgcac8040ttcaagacag aggctcagtt ccatggctta tttgtgctgt cacatcccgc atcctttaca8100agctcagtga tcatgtcagc tgatcatcca ggcctgacat tttccctccg cctcataagg8160agtgaaccaa cctataacca gccagtacag cagtggagct ttgtctctga ctttgccgta8220cgtgactact cagggaccta tactgtgaag ctggtgccat gcactgcccc atcacatcag8280gaataccgcc tgccagtcac ctgcaacccc agagaacctg tcacctttga ccttgacatc8340cgattccaac aggtcagtga tccagtggct gctgagttta gcttgaacac ccaaatgtac8400ctgctctcta agaagagtct ctggttgtct gatggatcca tgggattcgg gcaagagagt8460gatgttgctt ttgcagaagg tgatataatt tatggtcgtg tcatggtgga tcctgtccag8520aatctgggtg actcctttta ctgcagcatt gagaaggtgt ttctatgcac tggagctgat8580ggctatgttc ccaagtatag tccaatgaat gcagaatatg gctgcttagc cgactctcct8640tcactcttat atagatttaa aattgtggac aaagctcagc cagagacaca agcgaccagt8700tttggaaatg tcctatttaa tgccaaacta gcagtggatg accctgaagc cattctctta8760gtgaatcagc ctggatctga tggatttaaa gtcgactcaa caccactctt tcaggtcgct8820ctaggccgag aatggtatat acatacgatc tatacagtga gatcgaaaga caatgccaat8880cgaggtattg gcaaaagaag tgtggagtac cattctctgg tgagtcaagg aaagccccaa8940tccaccacca agagccggaa gaagagagag atcaggagca caccctcact ggcatgggag9000attggtgctg aaaacagtcg aggaacaaac atccagcaca ttgccctgga ccgcaccaag9060aggcagatcc cccatgggag agcacctcca gatggcatcc tcccctggga gctcaacagc9120cccagctctg cagtcagcct ggtcactgtg gtgggaggca ccacggtagg gttactcacc9180atctgcctca ctgtcattgc agtgctgatg tgcaggggca aggaaagttt cagggggaag9240gatgccccga aaggctccag cagcagtgag cccatggtgc ccccacagag ccatcacaat9300gacagctcag aagtttga 9318<210>37<211>1374<212>DNA<213>人(Homo sapiens)<400>37atggggtgta gtggagcctg gggcttgagc tgcccttgtc cacagacgcc atcctgggcc 60tggaggaaga tgcggacgcc atccatgagg aaccggagtg gcgccgtgtg gagcagggcc 120tctgtcccct tctctgcctg ggaagtagag gtgcagatga gggtgacggg actggggcgc 180cggggagccc agggcatggc cgtgtggtac acccggggca ggggccatgt aggctctgtc 240cttggggggc tggcttcgtg ggacggcatc gggatcttct ttgactctcc ggcagaggat 300actcaggaca gtcctgccat ccgtgtgctg gccagcgacg ggcacatccc ctctgagcag 360cctggggatg gagctagcca agggctgggc tcctgtcatt gggacttccg gaaccggcca 420caccccttca gagcacggat cacctactgg gggcagaggc tgcgcatgtc cttgaacagt 480ggcctcactc ccagtgatcc aggtgagttc tgtgtggatg tggggcccct gcttttggtc 540cctggaggtt tctttggggt ctcagcagcc accggcaccc tggcagatga tcatgatgtc 600ctgtccttcc tgaccttcag cctgagtgag cccagcccag aggttccccc tcagcccttc 660ctggagatgc agcacgtccg cctggcgagg cagctggaag ggctgtgggc aaggctgggc 720ttgggcacca gggaggatgt aactccaaaa tcagactctg aagctcaagg agaaggggaa 780aggctctttg acctggagga gacgctgggc agacaccgcc ggatcctgca ggctctgcgg 840ggtctctcca agcagctggc ccaggctgag agacaatgga agaagcagct gggcccccag 900gccaagccag gcctgacgga ggctggggat gcagctgtcc gcatggctgc agaagcccag 960gtctcctacc tgcctgtggg cattgagcat catttcttag agctggacca catcctgggc1020ctcctgcagg aggagcttcg gggcccggcg aaggcagcag ccaaggcccc ccgcccacct1080ggccagcccc caagggcctc ctcgtgcctg cagcctggca tcttcctgtt ctacctcctc1140attcagactg taggcttctt cggctacgtg cacttcaggc gcccggtgcc ccggccggcg1200aagaccatgg cgttcatggt gaagaccatg gtgggcggcc agctgaagaa cctcactggg1260agcctgggag gcggcgagga taagggagat ggggacaagt cggcagccga agctcagggc1320atgagccggg aggagtacga ggagtatcag aagcaactcg tggaagagaa gtga 1374<210>38<211>1581<212>DNA<213>人(Homo sapiens)<400>38atgccggcgg tcagtggtcc aggtccctta ttctgccttc tcctcctgct cctggacccc 60cacagccctg agacggggtg tcctcctcta cgcaggtttg agtacaagct cagcttcaaa 120ggcccaaggc tggcattgcc tggggctgga atacccttct ggagccatca tggagacgcc 180atcctgggcc tggaggaagt gcggctgacg ccatccatga ggaaccggag tggcgccgtg 240tggagcaggg cctctgtccc cttctctgcc tgggaagtag aggtgcagat gagggtgacg 300ggactggggc gccggggagc ccagggcatg gccgtgtggt acacccgggg caggggccat 360gtaggctctg tccttggggg gctggcttcg tgggacggca tcgggatctt ctttgactct 420ccggcagagg atactcagga cagtcctgcc atccgtgtgc tggccagcga cgggcacatc 480ccctctgagc agcctgggga tggagctagc caagggctgg gctcctgtca ttgggacttc 540cggaaccggc cacacccctt cagagcacgg atcacctact gggggcagag gctgcgcatg 600tccttgaaca gtggcctcac tcccagtgat ccaggtgagt tctgtgtgga tgtggggccc 660ctgcttttgg tccctggagg tttctttggg gtctcagcag ccaccggcac cctggcagat 720gatcatgatg tcctgtcctt cctgaccttc agcctgagtg agcccagccc agaggttccc 780cctcagccct tcctggagat gcagcacgtc cgcctggcga ggcagctgga agggctgtgg 840gcaaggctgg gcttgggcac cagggaggat gtaactccaa aatcagactc tgaagctcaa 900ggagaagggg aaaggctctt tgacctggag gagacgctgg gcagacaccg ccggatcctg 960caggctctgc ggggtctctc caagcagctg gcccaggctg agagacaatg gaagaagcag1020ctggggcccc caggccaagc caggcctgac ggaggctggg ccctggatgc ttcctgccag1080attccatcca ccccagggag gggtggccac ctctccatgt cactcaataa ggactctgcc1140aaggtcggtg ccctgctcca tggacagtgg actctgctcc aggccctgca agagatgagg1200gatgcagctg tccgcatggc tgcagaagcc caggtctcct acctgcctgt gggcattgag1260catcatttct tagagctgga ccacatcctg ggcctcctgc aggaggagct tcggggcccg1320gcgaaggcag cagccaaggc cccccgccca cctggccagc ccccaagggc ctcctcgtgc1380ctgcagcctg gcatcttcct gttctacctc ctcattcaga ctgtaggctt cttcggctac1440gtgcacttca ggcaggagct gaacaagagc cttcaggagt gtctgtccac aggcagcctt1500cctctgggtc ctgcaccaca cacccccagg gccctgggga ttctgaggag gcagcctctc1560cctgccagca tgcctgcctg a 1581<210>39<211>2715<212>DNA<213>人(Homo sapiens)<400>39atgctcttgg ctctatgttc atctctggct cttatttttg cagctcctgt cagtggacag 60cttgagcatt cagggaacta ctactgcaca gctgacaatg gctttggccc ccagcacagt 120gaggtggtga gtctctctgt cactgtccct gtgtctcatc ctgtcctcac cctcagctct 180gctgaggccc tgacttttga aggagccact gtgacacttc actcttcgct gatcctgcaa 240gctccacttt ctgtgtttga aggagacttc gtggttctga ggtgccgggc aaaggcggaa 300gtaacactga atactatgta caagaatggt aacgtcctga cattccttaa taaaagctct 360gacttccata ttcatcacgc aagtctcaaa gacaatggtg catatcactt tactggattt 420aacggaagta atttctctgt ttcttccaac atagtcaaaa tccaagtcca agagcatctc 480ctgccccagt ggttcctgaa ggcacctgat cccactgtgg cccttagtga gatattctca 540gtcaatagag gtccacttct gacaggcaca ggctcccgag ttatgactcc ctggatttac 600ttccctactg aggactggaa cttcactctt attcccatta ctgtggacga tgcttgcaaa 660aggccttgtg ctcctcgggc tccttgggaa gttggaagtc taacaccagg aaagagtttc 720cagcagaagg ggaacccaga cctgctcatg ggcccttttg atgttcttca cttgtccctc 780atcacacttt tttgcaacat ggcaggttct ttgttttatt atatggaact tggagaaaag 840aaagatgcat tatttgttac aggaaatgaa agcagaagct atcattggtt ccagaagttc 900agccttgctg gtgggcaaga agcagatcaa aagttgtggt ttccccctgg actgatgagt 960caggatattt tcatatatat cagacaaggt gagagttgtc ttgtgattga gatgtttcat1020caggtctaca gacggcctgc tggaggtgtt ccagtagagc atatgagtgt atgggctctc1080agggtgaata gttcgggact cttcgcctac gctgatggct ggctctttac tctctttcag1140ctccagtctg tggacaatct gagcccatca actcagtctc aaacacacga aggccatgaa1200aagttatgtc ccttcctggc catagggcca cctgcacata gcaggggcag cttcctcaga1260gcaaagaaga gtctagttgc atacatcaaa ggaaatcaac tctccttccc tccagtagaa1320gacctattgc ctaagtccca atggccctgc atccaggtgc ttcccaggaa tatagctgca1380gctgcacaca aacctgtgat ttccgtccat cctccatgga ccacattctt caaaggagag1440agagtgactc tgacttgcaa tggatttcag ttctatgcaa cagagaaaac aacatggtat1500catcggcact actggggaga aaagttgacc ctgaccccag gaaacaccct cgaggttcgg1560gaatctggac tgtacagatg ccaggcccgg ggctccccac gaagtaaccc tgtgcgcttg1620ctcttttctt caggtgagaa agaagactgt gtctctgaca agaatcctgc tacaaatcac1680actccaatgt ccaggaagag atcctcatgt agttctctaa gtgccacttc tttcatagct1740cctgctctga gactcgactc cttaatcctg caggcaccat attctgtgtt tgaaggtgac1800acattggttc tgagatgcca cagaagaagg aaagagaaat tgactgctgt gaaatatact1860tggaatggaa acattctttc catttctaat aaaagctggg atcttcttat cccacaagca1920agttcaaata acaatggcaa ttatcgatgc attggatatg gagacgagaa tgatgtattt1980agatcaaatt tcaaaataat taaaattcaa gggatccctg tgtctggggt gctcctggag2040acccagccct cagggggcca ggctgttgaa ggggagatgc tggtccttgt ctgctccgtg2100gctgaaggca caggggatac cacattctcc tggcaccgag aggacatgca ggagagtctg2160gggaggaaaa ctcagcgttc cctgagagca gagctggagc tccctgccat cagacagagc2220catgcagggg gatactactg tacagcagac aacagctacg gccctgtcca gagcatggtg2280ctgaatgtca ctgtgagaga gaccccaggc aacagagatg gccttgtcgc cgcgggagcc2340actggagggc tgctcagtgc tcttctcctg gctgtggccc tgctgtttca ctgctggcgt2400cggaggaagt cagtacaccc caaaaaggga gatttggtat actctgagat ccagactact2460cagctgggag aagaagagga aggaaatcat ggcaataaaa atcaagaact agaacttgtt2520aatgtaggag agagtttttc tcacagggca tgcatatgga gtactctaat gggaacttgc2580caaacaatcg ggggtgctaa tacctccagg acacttctag aggataagga tgtctcagtt2640gtctactctg aggtaaagac acaacaccca gataactcag ctggaaagat cagctctaag2700gatgaagaaa gttaa 2715<210>40<211>1548<212>DNA<213>人(Homo sapiens)<400>40atgctgctgt gggcgtcctt gctggccttt gctccagtct gtggacaatc tgcagctgca 60cacaaacctg tgatttccgt ccatcctcca tggaccacat tcttcaaagg agagagagtg 120actctgactt gcaatggatt tcagttctat gcaacagaga aaacaacatg gtatcatcgg 180cactactggg gagaaaagtt gaccctgacc ccaggaaaca ccctcgaggt tcgggaatct 240ggactgtaca gatgccaggc ccggggctcc ccacgaagta accctgtgcg cttgctcttt 300tcttcagact ccttaatcct gcaggcacca tattctgtgt ttgaaggtga cacattggtt 360ctgagatgcc acagaagaag gaaagagaaa ttgactgctg tgaaatatac ttggaatgga 420aacattcttt ccatttctaa taaaagctgg gatcttctta tcccacaagc aagttcaaat 480aacaatggca attatcgatg cattggatat ggagatgaga atgatgtatt tagatcaaat 540ttcaaaataa ttaaaattca agaactattt ccacatccag agctgaaagc tacagactct 600cagcctacag aggggaattc tgtaaacctg agctgtgaaa cacagcttcc tccagagcgg 660tcagacaccc cacttcactt caacttcttc agagatggcg aggtcatcct gtcagactgg 720agcacgtacc cggaactcca gctcccaacc gtctggagag aaaactcagg atcctattgg 780tgtggtgctg aaacagtgag gggtaacatc cacaagcaca gtccctcgct acagatccat 840gtgcagcgga tccctgtgtc tggggtgctc ctggagaccc agccctcagg gggccaggct 900gttgaagggg agatgctggt ccttgtctgc tccgtggctg aaggcacagg ggataccaca 960ttctcctggc accgagagga catgcaggag agtctgggga ggaaaactca gcgttccctg1020agagcagagc tggagctccc tgccatcaga cagagccatg cagggggata ctactgtaca1080gcagacaaca gctacggccc tgtccagagc atggtgctga atgtcactgt gagagagacc1140ccaggcaaca gagatggcct tgtcgccgcg ggagccactg gagggctgct cagtgctctt1200ctcctggctg tggccctgct gtttcactgc tggcgtcgga ggaagtcagg agttggtttc1260ttgggagacg aaaccaggct ccctcccgct ccaggcccag gagagtcctc ccattccatc1320tgccctgccc aggtggagct tcagtcgttg tatgttgatg tacaccccaa aaagggagat1380ttggtatact ctgagatcca gactactcag ctgggagaag aagaggaagc taatacctcc1440aggacacttc tagaggataa ggatgtctca gttgtctact ctgaggtaaa gacacaacac1500ccagataact cagctggaaa gatcagctct aaggatgaag aaagttaa 1548<210>41<211>2494<212>DNA<213>人(Homo sapiens)<400>41batggctgtg ggaggaggac acaaaggagt tagatgtcct ccctctgctc gcagctccca 60ggtgcccacg tgctgcgctg gctggaggca gcaaggggac gagtgtggga ttgcggtgtg 120cgaaggcaac tccacgtgct cagagaacga ggtgtgcgtg aggcctggcg agtgccgctg 180ccgccacggc tacttcggtg ccaactgcga caccaagtgc ccgcgccagt tctggggccc 240cgactgcaag gagctgtgta gctgccaccc acacgggcag tgcgaggacg tgacaggcca 300gtgtacttgt cacgcgcggc gctggggcgc gcgctgcgag catgcgtgcc agtgccagca 360cggcacgtgc cacccccgga gcggcgcgtg ccgctgtgag tccggctggt ggggcgcgca 420gtgcgccagc gcgtgctact gcagcgccac gtcgcgctgc gacccacaga ccggcgcctg 480cctgtgccac gcaggctggt ggggccgcag ctgcaacaac cagtgcgcct gcaactcgtc 540tccctgcgag cagcagagcg gccgctgtca gtgccgcgag cgtacgttcg gcgcgcgctg 600cgatcgctac tgccagtgct tccgcggccg ctgccaccct gtggacggca cgtgtgcctg 660cgagccgggc taccgcggca agtactgtcg cgagccgtgc cccgccggct tctacggctt 720gggctgtcgc cgccggtgtg gccagtgcaa gggccagcag ccgtgcacgg tggccgaggg 780ccgctgcttg acgtgcgagc ccggctggaa cggaaccaag tgcgaccagc cttgcgccac 840cggtttctat ggcgagggct gcagccaccg ctgtccgcca tgccgcgacg ggcatgcctg 900taaccatgtc accggcaagt gtacgcgctg caacgcgggc tggatcggcg accggtgcga 960gaccaagtgt agcaatggca cttacggcga ggactgcgcc ttcgtgtgcg ccgactgcgg1020cagcggacac tgcgacttcc agtcggggcg ctgcctgtgc agccctggcg tccacgggcc1080ccactgtaac gtgacgtgcc cgcccggact ccacggcgcg gactgtgctc aggcctgcag1140ctgccacgag gacacgtgcg acccggtcac tggtgcctgc cacctagaaa ccaaccagcg1200caagggcgtg atgggcgcgg gcgcgctgct cgtcctgctc gtctgcctgc tgctctcgct1260gctcggctgc tgctgcgctt gccgcggcaa ggaccctacg cgccgacccc gcccccgcag1320ggagctttcg cttgggagga agaaggcgcc gcaccgacta tgcgggcgct tcagtcgcat1380cagcatgaag ctgccccgga tcccgctccg gaggcagaaa ctacccaaag tcgtagtggc1440ccaccacgac ctggataaca cactcaactg cagcttcctg gagccaccct cagggctgga1500gcagccctca ccatcctggt cctctcgggc ctccttctcc tcgtttgaca ccactgatga1560aggccctgtg tactgtgtac cccatgagga ggcaccagcg gagagccggg accccgaagt1620ccccactgtc cctgccgagg cgccggcgcc gtcccctgtg cccttgacca cgccagcctc1680cgccgaggag gcgatacccc tccccgcgtc ctccgacagc gagcggtcgg cgtccagcgt1740ggaggggccc ggaggggctc tgtacgcgcg cgtggcccga cgcgaggccc ggccggcccg1800ggcccggggc gagattgggg gcctgtcgct gtcgccatcg cccgagcgca ggaaaccgcc1860gccacctgac cccgccacca agcctaaggt gtcctggatc cacggcaagc acagcgccgc1920tgcagctggc cgtgcgccct caccaccgcc gccaggctcc gaggccgcgc ccagccccag1980caagaggaaa cggacgccca gcgacaaatc ggcgcatacg gtcgaacacg gcagcccccg2040gacccgcgac ccaacgccgc gccccccggg gctgcccgag gaggcgacag ccctcgctgc2100gccctcgccg cccagggccc gagcgcgcgc cgcgccccgg cctcttggag cccacggacg2160ccggcggtcc cccgcgaagc gcgccgaggc tgcctccatg ttggccgctg acgtgcgcgg2220caagactcgc agcctgggcc gcgccgaggt ggccctgggc gcgcagggcc ccagggaaaa2280gccggcgccc ccacagaaag ccaagcgctc cgtgccgcca gcctcgcccg cccgcgcgcc2340cccagcgacc gaaaccccgg ggcctgagaa ggcggcgacc gacttgcccg cgcctgagac2400cccccggaag aagaccccca tccagaagcc gccgcgcaag aagagccggg aggcggcggg2460cgagctgggc agggcgggcg cacccaccct gtag2494<210>42<211>2614<212>DNA<213>人(Homo sapiens)<400>42batggagggc gcagggcccc ggggggccgg gccggcgcgg cgccggggag ccggggggcc 60gccgtcaccg ctgctgccgt cgctgctgct gctgctgctg ctctggatgc tgccggacac 120cgtggcgcct caggaactga accctcgcgg ccgcaacgtg tgccgtgctc ccggctccca 180ggtgcccacg tgctgcgctg gctggaggca gcaaggggac gagtgtggga ttgcggtgtg 240cgaaggcaac tccacgtgct cagagaacga ggtgtgcgtg aggcctggcg agtgccgctg 300ccgccacggc tacttcggtg ccaactgcga caccaagtgc ccgcgccagt tctggggccc 360cgactgcaag gagctgtgta gctgccaccc acacgggcag tgcgaggacg tgacaggcca 420gtgtacttgt cacgcgcggc gctggggcgc gcgctgcgag catgcgtgcc agtgccagca 480cggcacgtgc cacccccgga gcggcgcgtg ccgctgtgag tccggctggt ggggcgcgca 540gtgcgccagc gcgtgctact gcagcgccac gtcgcgctgc gacccacaga ccggcgcctg 600cctgtgccac gcaggctggt ggggccgcag ctgcaacaac cagtgcgcct gcaactcgtc 660tccctgcgag cagcagagcg gccgctgtca gtgccgcgag cgtacgttcg gcgcgcgctg 720cgatcgctac tgccagtgct tccgcggccg ctgccaccct gtggacggca cgtgtgcctg 780cgagccgggc taccgcggca agtactgtcg cgagccgtgc cccgccggct tctacggctt 840gggctgtcgc cgccggtgtg gccagtgcaa gggccagcag ccgtgcacgg tggccgaggg 900ccgctgcttg acgtgcgagc ccggctggaa cggaaccaag tgcgaccagc cttgcgccac 960cggtttctat ggcgagggct gcagccaccg ctgtccgcca tgccgcgacg ggcatgcctg1020taaccatgtc accggcaagt gtacgcgctg caacgcgggc tggatcggcg accggtgcga1080gaccaagtgt agcaatggca cttacggcga ggactgcgcc ttcgtgtgcg ccgactgcgg1140cagcggacac tgcgacttcc agtcggggcg ctgcctgtgc agccctggcg tccacgggcc1200ccactgtaac gtgacgtgcc cgcccggact ccacggcgcg gactgtgctc aggcctgcag1260ctgccacgag gacacgtgcg acccggtcac tggtgcctgc cacctagaaa ccaaccagcg1320caagggcgtg atgggcgcgg gcgcgctgct cgtcctgctc gtctgcctgc tgctctcgct1380gctcggctgc tgctgcgctt gccgcggcaa ggaccctacg cgccgacccc gcccccgcag1440ggagctttcg cttgggagga agaaggcgcc gcaccgacta tgcgggcgct tcagtcgcat1500cagcatgaag ctgccccgga tcccgctccg gaggcagaaa ctacccaaag tcgtagtggc1560ccaccacgac ctggataaca cactcaactg cagcttcctg gagccaccct cagggctgga1620gcagccctca ccatcctggt cctctcgggc ctccttctcc tcgtttgaca ccactgatga1680aggccctgtg tactgtgtac cccatgagga ggcaccagcg gagagccggg accccgaagt1740ccccactgtc cctgccgagg cgccggcgcc gtcccctgtg cccttgacca cgccagcctc1800cgccgaggag gcgatacccc tccccgcgtc ctccgacagc gagcggtcgg cgtccagcgt1860ggaggggccc ggaggggctc tgtacgcgcg cgtggcccga cgcgaggccc ggccggcccg1920ggcccggggc gagattgggg gcctgtcgct gtcgccatcg cccgagcgca ggaaaccgcc1980gccacctgac cccgccacca agcctaaggt gtcctggatc cacggcaagc acagcgccgc2040tgcagctggc cgtgcgccct caccaccgcc gccaggctcc gaggccgcgc ccagccccag2100caagaggaaa cggacgccca gcgacaaatc ggcgcatacg gtcgaacacg gcagcccccg2160gacccgcgac ccaacgccgc gccccccggg gctgcccgag gaggcgacag ccctcgctgc2220gccctcgccg cccagggccc gagcgcgcgc cgcgccccgg cctcttggag cccacggacg2280ccggcggtcc cccgcgaagc gcgccgaggc tgcctccatg ttggccgctg acgtgcgcgg2340caagactcgc agcctgggcc gcgccgaggt ggccctgggc gcgcagggcc ccagggaaaa2400gccggcgccc ccacagaaag ccaagcgctc cgtgccgcca gcctcgcccg cccgcgcgcc2460cccagcgacc gaaaccccgg ggcctgagaa ggcggcgacc gacttgcccg cgcctgagac2520cccccggaag aagaccccca tccagaagcc gccgcgcaag aagagccggg aggcggcggg2580cgagctgggc agggcgggcg cacccaccct gtag 2614<210>43<211>402<212>DNA<213>人(Homo sapiens)<400>43atcgactgcc gcgcggagca gggccgtacg ccgctcatgg tggccgtggg gctgccggac 60cccgcgctgc gcgcgcgctt cgtgcggctg ctgctcgagc agggtgctgc agtgaacctg 120cgagacgagc gcggccgcac cgcactcagc ctggcgtgcg agcgaggcca cctggacgcc 180gtgcagctgc tggtgcagtt cagcggtgac cccgaggcgg ccgactctgc gggcaacagc 240ccggtgatgt gggcggcggc ctgcggccac ggggcggtgc tcgagttcct ggtgcggtcc 300ttccgccgcc taggcctgcg cctcgaccgc accaaccgtg cggggctcac cgcgctgcaa 360ctggccgccg cccgcggcca cgggacctgt gtgcaggccc tc402<210>44<211>975<212>DNA<213>人(Homo sapiens)<400>44atgctcaaac ccaaggacct gtgcccccga gcggggacgc gcaccttcct ggaggccatg 60caggcgggca aagtgcactt ggcccgcttc gtgttggatg cgctggaccg cagcatcatc 120gactgccgcg cggagcaggg ccgtacgccg ctcatggtgg ccgtggggct gccggacccc 180gcgctgcgcg cgcgcttcgt gcggctgctg ctcgagcagg gtgctgcagt gaacctgcga 240gacgagcgcg gccgcaccgc actcagcctg gcgtgcgagc gaggccacct ggacgccgtg 300cagctgctgg tgcagttcag cggtgacccc gaggcggccg actctgcggg caacagcccg 360gtgatgtggg cggcggcctg cggccacggg gcggtgctcg agttcctggt gcggtccttc 420cgccgcctag gcctgcgcct cgaccgcacc aaccgtgcgg ggctcaccgc gctgcaactg 480gccgccgccc gcggccacgg gacctcggcg ggcggccacg gcggcgaggc tggctcagcg 540ggcaagaatt cgggccggca ccgggcgcag ggcagcgaac ggcccgagct gggtcggagc 600atgagcctgg ctctaggtgc ggtaaccgag gaggaggctg cccgcctgcg ggctggggcc 660ctgatggccc taccaaactc gccccagtct tcggggactg ggcggtggcg ctcacaggag 720gtgctggagg gagcgccccc aaccttagcg caagccccca ttggcctcag tccccacccg 780gagggcggcc ccggctctgg ccgcctgggt ttgcgccgac gctccacagc cccagatatc 840cccagcctgg tcggggaggc gccagggccc gagagtggcc cggagttaga ggccaacgct 900ctgtctgtct cggtgcctgg gccgaaccct tggcaggcgg gcaccgaggc tgtggtgctg 960cgtgctcagc ggtaa 975<210>45<211>568<212>PRT<213>人(Homo sapiens)<400>45Met Lys Glu Ala Glu Met Asp Gly Glu Ala Val Arg Phe Cys Thr Asp1 5 10 15Asn Gln Cys Val SeT Leu His Pro Gln Glu Val Asp Ser Val Ala Met20 25 30Ala Pro Ala Ala Pro Lys Ile Pro Arg Leu Val Gln Ala Thr Pro Ala35 40 45Phe Met Ala Val Thr Leu Val Phe Ser Leu Val Thr Leu Phe Val Val50 55 60Gly Lys Pro Pro Val Gln Gln Gln Thr Arg Pro Val Pro Lys Pro Val65 70 75 80Gln Ala Val Ile Leu Gly Asp Asn Ile Thr Gly His Leu Pro Phe Glu85 90 95Pro Asn Asn His His His Phe Gly Arg Glu Ala Glu Met Arg Glu Leu100 105 110Ile Gln Thr Phe Lys Gly His Met Glu Asn Ser Ser Ala Trp Val Val115 120 125Glu Ile Gln Met Leu Lys Cys Arg Val Asp Asn Val Asn Ser Gln Leu130 135 140Gln Val Leu Gly Asp His Leu Gly Asn Thr Asn Ala Asp Ile Gln Met145 150 155 160Val Lys Gly Val Leu Lys Asp Ala Thr Thr Leu Ser Leu Gln Thr Gln165 170 175Met Leu Arg Ser Ser Leu Glu Gly Thr Asn Ala Glu I1e Gln Arg Leu180 185 190Lys Glu Asp Leu Glu Lys Ala Asp Ala Leu Thr Phe Gln Thr Leu Asn195 200 205Phe Leu Lys Ser Ser Leu Glu Asn Thr Ser Ile Glu Leu His Val Leu210 215 220Ser Arg Gly Leu Glu Asn Ala Asn Ser Glu Ile Gln Met Leu Asn Ala225 230 235 240Arg Ala Asn Ala Glu Ile Gln Gly Leu Lys Glu Asn Leu Gln Asn Thr245 250 255Asn Ala Leu Asn Ser Gln Thr Gln Ala Phe Ile Lys Ser Ser Phe Asp260 265 270Asn Thr Ser Ala Glu Ile Gln Phe Leu Arg Gly His Leu Glu Arg Ala275 280 285Gly Asp Glu Ile His Val Leu Lys Arg Asp Leu Lys Met Val Thr Ala290 295 300Gln Thr Gln Lys Ala Asn Gly Arg Leu Asp Gln Thr Asp Thr Gln Ile305 310 315 320Gln Val Phe Lys Ser Glu Met Glu Asn Val Asn Thr Leu Asn Ala Gln325 330 335Ile Gln Val Leu Asn Gly His Met Lys Asn Ala Ser Arg Glu Ile Gln340 345 350Thr Leu Lys Gln Gly Met Lys Asn Ala Ser Ala Leu Thr Ser Gln Thr355 360 365Gln Met Leu Asp Ser Asn Leu Gln Lys Ala Ser Ala Glu Ile Gln Arg370 375 380Leu Arg Gly Asp Leu Glu Asn Thr Lys Ala Leu Thr Met Glu Ile Gln385 390 395 400Gln Glu Gln Ser Arg Leu Lys Thr Leu His Val Val Ile Thr Ser Gln405 410 415Glu Gln Leu Gln Arg Thr Gln Ser Gln Leu Leu Gln Met Val Leu Gln420 425 430Gly Trp Lys Phe Asn Gly Gly Ser Leu Tyr Tyr Phe Ser Ser Val Lys435 440 445Lys Ser Trp His Glu Ala Glu Gln Phe Cys Val Ser Gln Gly Ala His450 455 460Leu Ala Ser Val Ala Ser Lys Glu Glu Gln Ala Phe Leu Val Glu Phe465 470 475 480Thr Ser Lys Val Tyr Tyr Trp Ile Gly Leu Thr Asp Arg Gly Thr Glu485 490 495Gly Ser Trp Arg Trp Thr Asp Gly Thr Pro Phe Asn Ala Ala Gln Asn500 505 510Lys Ala Pro Val Val Phe Gly Phe Trp Glu Lys Asn Gln Ser Asp Asn515 520 525Trp Arg His Lys Asn Gly Gln Thr Glu Asp Cys Val Gln Ile Gln Gln530 535 540Lys Trp Asn Asp Met Thr Cys Asp Thr Pro Tyr Gln Trp Val Cys Lys545 550 555 560Lys Pro Met Gly Gln Gly Val Ala565<210>46<211>364<212>PRT<213>人(Homo sapiens)<400>46Met Ser Arg Gln Gly Lys Leu Phe Ser Ala Phe Gly Val Gly Cys Cys1 5 10 15Val Thr Ala Gly Leu Pro Lys Asp Asp Asn Thr Pro Ser Thr Ile Ala20 25 30Asp Val His Asn Gly Tyr Thr Met Asn Val Val Glu Gln Val Leu Lys35 40 45Asp Ser Phe Val Leu Phe Phe Pro Gly Thr Leu Cys Asp Phe Pro Lys50 55 60Ile His His Gly Phe Leu Tyr Asp Glu Glu Asp Tyr Asn Pro Phe Ser65 70 75 80Gln Val Pro Thr Gly Glu Val Phe Tyr Tyr Ser Cys Glu Tyr Asn Phe85 90 95Val Ser Pro Ser Lys Ser Phe Trp Thr Arg Ile Thr Cys Thr Glu Glu100 105 110Gly Trp Ser Pro Thr Pro Lys Cys Leu Arg Met Cys Ser Phe Pro Phe115 120 125Val Lys Asn Gly His Ser Glu Ser Ser Gly Leu Ile His Leu Glu Gly130 135 140Asp Thr Val Gln Ile Ile Cys Asn Thr Gly Tyr Ser Leu Gln Asn Asn145 150 155 160Glu Lys Asn Ile Ser Cys Val Glu Arg Gly Trp Ser Thr Pro Pro Ile165 170 175Cys Ser Phe Thr Met Lys Thr Cys Gly Tyr Ile Pro Glu Leu Glu Tyr180 185 190Gly Tyr Val Gln Pro Ser Val Pro Pro Tyr Gln His Gly Val Ser Val195 200 205Glu Val Asn Cys Arg Asn Glu Tyr Ala Met Ile Gly Asn Asn Met Ile210 215 220Thr Cys Ile Asn Gly Ile Trp Thr Glu Leu Pro Met Cys Val Glu Ser225 230 235 240Thr Ala Tyr Cys Gly Pro Pro Pro Ser Ile Asn Asn Gly Asp Thr Thr245 250 255Ser Phe Pro Leu Ser Val Tyr Pro Pro Gly Ser Thr Val Thr Tyr Arg260 265 270Cys Gln Ser Phe Tyr Lys Leu Gln Gly Ser Val Thr Val Thr Cys Arg275 280 285Asn Lys Gln Trp Ser Glu Pro Pro Arg Cys Leu Asp Pro Cys Val Val290 295 300Ser Glu Glu Asn Met Asn Lys Asn Asn Ile Gln Leu Lys Trp Arg Asn305 310 315 320Asp Gly Lys Leu Tyr Ala Lys Thr Gly Asp Ala Val Glu Phe Gln Cys325 330 335Lys Phe Pro His Lys Ala Met Ile Ser Ser Pro Pro Phe Arg Ala Ile340 345 350Cys Gln Glu Gly Lys Phe Glu Tyr Pro Ile Cys Glu355 360<210>47<211>327<212>PRT<213>人(Homo sapiens)<400>47Met Leu Leu Leu Phe Ser Val Ile Leu Ile Ser Trp Val Ser Thr Val1 5 10 15Gly Gly Glu Gly Thr Leu Cys Asp Phe Pro Lys Ile His His Gly Phe20 25 30Leu Tyr Asp Glu Glu Asp Tyr Asn Pro Phe Ser Gln Val Pro Thr Gly35 40 45Glu Val Phe Tyr Tyr Ser Cys Glu Tyr Asn Phe Val Ser Pro Ser Lys50 55 60Ser Phe Trp Thr Arg Ile Thr Cys Thr Glu Glu Gly Trp Ser Pro Thr65 70 75 80Pro Lys Cys Leu Arg Met Cys Ser Phe Pro Phe Val Lys Asn Gly His85 90 95Ser Glu Ser Ser Gly Leu Ile His Leu Glu Gly Asp Thr Val Gln Ile100 105 110lle Cys Asn Thr Gly Tyr Ser Leu Gln Asn Asn Glu Lys Asn Ile Ser115 120 125Cys Val Glu Arg Gly Trp Ser Thr Pro Pro Ile Cys Ser Phe Thr Met130 135 140Lys Thr Cys Gly Tyr Ile Pro Glu Leu Glu Tyr Gly Tyr Val Gln Pro145 150 155 160Ser Val Pro Pro Tyr Gln His Gly Val Ser Val Glu Val Asn Cys Arg165 170 175Asn Glu Tyr Ala Met Ile Gly Asn Asn Met Ile Thr Cys Ile Asn Gly180 185 190Ile Trp Thr Glu Leu Pro Met Cys Val Glu Ser Thr Ala Tyr Cys Gly195 200 205Pro Pro Pro Ser Ile Asn Asn Gly Asp Thr Thr Ser Phe Pro Leu Ser210 215 220Val Tyr Pro Pro Gly Ser Thr Val Thr Tyr Arg Cys Gln Ser Phe Tyr225 230 235 240Lys Leu Gln Gly Ser Val Thr Val Thr Cys Arg Asn Lys Gln Trp Ser245 250 255Glu Pro Pro Arg Cys Leu Asp Pro Cys Val Val Ser Glu Glu Asn Met260 265 270Asn Lys Asn Asn Ile Gln Leu Lys Trp Arg Asn Asp Gly Lys Leu Tyr275 280 285Ala Lys Thr Gly Asp Ala Val Glu Phe Gln Cys Lys Phe Pro His Lys290 295 300Ala Met Ile Ser Ser Pro Pro Phe Arg Ala Ile Cys Gln Glu Gly Lys305 310 315 320Phe Glu Tyr Pro Ile Cys Glu325<210>48<211>154<212>PRT<213>人(Homo sapiens)<400>48Met Ala Pro Ala Arg Ala Gly Cys Cys Pro Leu Leu Leu Leu Leu Leu1 5 10 15Gly Leu Trp Val Ala Glu Val Leu Val Arg Ala Lys Pro Lys Asp Met20 25 30Thr Ser Ser Gln Trp Phe Lys Thr Gln His Val Gln Pro Ser Pro Gln35 40 45Ala Cys Asn Ser Ala Met Ser Ile Ile Asn Lys Tyr Thr Glu Arg Cys50 55 60Lys Asp Leu Asn Thr Phe Leu His Glu Pro Phe Ser Ser Val Ala Ile65 70 75 80Thr Cys Gln Thr Pro Asn Ile Ala Cys Lys Asn Ser Cys Lys Asn Cys85 90 95His Gln Ser His Gly Pro Met Ser Leu Thr Met Gly Glu Leu Thr Ser100 105 110Gly Lys Tyr Pro Asn Cys Arg Tyr Lys Glu Lys His Leu Asn Thr Pro115 120 125Tyr Ile Val Ala Cys Asp Pro Pro Gln Gln Gly Asp Pro Gly Tyr Pro130 135 140Leu Val Pro Val His Leu Asp Lys Val Val145 150<210>49<211>502<212>PRT<213>人(Homo sapiens)<400>49Met Arg Gln Leu Gly Gly Ser Leu Arg Pro Pro Arg Ala Ala His Gly1 5 10 15Ala Glu Pro Leu Pro Ser Ala Leu Gly Pro Cys Ala Gly Gly Asp Arg20 25 30Asp Leu Gly Arg Gly Thr Pro Gly Trp Glu Pro Arg Arg Ala Arg Val35 40 45Pro Ile His Glu Gln Val Asp Pro Pro Arg Glu Gly Pro His Leu Phe50 55 60Gln Asn Leu Leu Leu Phe Leu Trp Ala Leu Leu Asn Cys Gly Leu Gly65 70 75 80Val Ser Ala Gln Gly Pro Gly Glu Trp Thr Pro Trp Val Ser Trp Thr85 90 95Arg Cys Ser Ser Ser Cys Gly Arg Gly Val Ser Val Arg Ser Arg Arg100 105 110Cys Leu Arg Leu Pro Gly Glu Glu Pro Cys Trp Gly Asp Ser His Glu115 120 125Tyr Arg Leu Cys Gln Leu Pro Asp Cys Pro Pro Gly Ala Val Pro Phe130 135 140Arg Asp Leu Gln Cys Ala Leu Tyr Asn Gly Arg Pro Val Leu Gly Thr145 150 155 160Gln Lys Thr Tyr Gln Trp Val Pro Phe His Gly Ala Pro Asn Gln Cys165 170 175Asp Leu Asn Cys Leu Ala Glu Gly His Ala Phe Tyr His Ser Phe Gly180 185 190Arg Val Leu Asp Gly Thr Ala Cys Ser Pro Gly Ala Gln Gly Val Cys195 200 205Val Ala Gly Arg Cys Leu Ser Ala Gly Cys Asp Gly Leu Leu Gly Ser210 215 220Gly Ala Leu Glu Asp Arg Cys Gly Arg Cys Gly Gly Ala Asn Asp Ser225 230 235 240Cys Leu Phe Val Gln Arg Val Phe Arg Asp Ala Gly Ala Phe Ala Gly245 250 255Tyr Trp Asn Val Thr Leu Ile Pro Glu Gly Ala Arg His Ile Arg Val260 265 270Glu His Arg Ser Arg Asn His Leu Gly Ile Leu Gly Ser Leu Met Gly275 280 285Gly Asp Gly Arg Tyr Val Leu Asn Gly His Trp Val Val Ser Pro Pro290 295 300Gly Thr Tyr Glu Ala Ala Gly Thr His Val Val Tyr Thr Arg Asp Thr305 310 315 320Gly Pro Gln Glu Thr Leu Gln Ala Ala Gly Pro Thr Ser His Asp Leu325 330 335Leu Leu Gln Val Leu Leu Gln Glu Pro Asn Pro Gly Ile Glu Phe Glu340 345 350Phe Trp Leu Pro Arg Glu Arg Tyr Ser Pro Phe Gln Ala Arg Val Gln355 360 365Ala Leu Gly Trp Pro Leu Arg Gln Pro Gln Pro Arg Gly Val Glu Pro370 375 380Gln Pro Pro Ala Ala Pro Ala Val Thr Pro Ala Gln Thr Pro Thr Leu385 390 395 400Ala Pro Val Phe Gln Ala Arg Val Leu Gly His His His Gln Ala Gln405 410 415Glu Thr Arg Tyr Glu Val Arg Ile Gln Leu Val Tyr Lys Asn Arg Ser420 425 430Pro Leu Arg Ala Arg Glu Tyr Val Trp Ala Pro Gly His Cys Pro Cys435 440 445Pro Met Leu Ala Pro His Arg Asp Tyr Leu Met Ala Val Gln Arg Leu450 455 460Val Ser Pro Asp Gly Thr Gln Asp Gln Leu Leu Leu Pro His Ala Gly465 470 475 480Tyr Ala Arg Pro Trp Ser Pro Ala Glu Asp Ser Arg Ile Arg Leu Thr485 490 495Ala Arg Arg Cys Pro Gly500<210>50<211>451<212>PRT<213>人(Homo sapiens)<400>50Met Asp Ser Ala Pro Leu Phe Pro Arg Pro Hi s Leu Phe Gln Asn Leu1 5 10 15Leu Leu Phe Leu Trp Ala Leu Leu Asn Cys Gly Leu Gly Val Ser Ala20 25 30Gln Gly Pro Gly Glu Trp Thr Pro Trp Val Ser Trp Thr Arg Cys Ser35 40 45Ser Ser Cys Gly Arg Gly Val Ser Val Arg Ser Arg Arg Cys Leu Arg50 55 60Leu Pro Gly Glu Glu Pro Cys Trp Gly Asp Ser His Glu Tyr Arg Leu65 70 75 80Cys Gln Leu Pro Asp Cys Pro Pro Gly Ala Val Pro Phe Arg Asp Leu85 90 95Gln Cys Ala Leu Tyr Asn Gly Arg Pro Val Leu Gly Thr Gln Lys Thr100 105 110Tyr Gln Trp Val Pro Phe His Gly Ala Pro Asn Gln Cys Asp Leu Asn115 120 125Cys Leu Ala Glu Gly His Ala Phe Tyr His Ser Phe Gly Arg Val Leu130 135 140Asp Gly Thr Ala Cys Ser Pro Gly Ala Gln Gly Val Cys Val Ala Gly145 150 155 160Arg Cys Leu Ser Ala Gly Cys Asp Gly Leu Leu Gly Ser Gly Ala Leu165 170 175Glu Asp Arg Cys Gly Arg Cys Gly Gly Ala Asn Asp Ser Cys Leu Phe180 185 190Val Gln Arg Val Phe Arg Asp Ala Gly Ala Phe Ala Gly Tyr Trp Asn195 200 205Val Thr Leu Ile Pro Glu Gly Ala Arg His Ile Arg Val Glu His Arg210 215 220Ser Arg Asn His Leu Gly Ile Leu Gly Ser Leu Met Gly Gly Asp Gly225 230 235 240Arg Tyr Val Leu Asn Gly His Trp Val Val Ser Pro Pro Gly Thr Tyr245 250 255Glu Ala Ala Gly Thr His Val Val Tyr Thr Arg Asp Thr Gly Pro Gln260 265 270Glu Thr Leu Gln Ala Ala Gly Pro Thr Ser His Asp Leu Leu Leu Gln275 280 285Val Leu Leu Gln Glu Pro Asn Pro Gly Ile Glu Phe Glu Phe Trp Leu290 295 300Pro Arg Glu Arg Tyr Ser Pro Phe Gln Ala Arg Val Gln Ala Leu Gly305 310 315 320Trp Pro Leu Arg Gln Pro Gln Pro Arg Gly Val Glu Pro Gln Pro Pro325 330 335Ala Ala Pro Ala Val Thr Pro Ala Gln Thr Pro Thr Leu Ala Pro Val340 345 350Phe Gln Ala Arg Val Leu Gly His His His Gln Ala Gln Glu Thr Arg355 360 365Tyr Glu Val Arg Ile Gln Leu Val Tyr Lys Asn Arg Ser Pro Leu Arg370 375 380Ala Arg Glu Tyr Val Trp Ala Pro Gly His Cys Pro Cys Pro Met Leu385 390 395 400Ala Pro His Arg Asp Tyr Leu Met Ala Val Gln Arg Leu Val Ser Pro405 410 415Asp Gly Thr Gln Asp Gln Leu Leu Leu Pro His Ala Gly Tyr Ala Arg420 425 430Pro Trp Ser Pro Ala Glu Asp Ser Arg Ile Arg Leu Thr Ala Arg Arg435 440 445Cys Pro Gly450<210>51<211>431<212>PRT<213>人(Homo sapiens)<400>51Met Ile Arg Thr Pro Leu Ser Ala Ser Ala Hi s Arg Leu Leu Leu Pro1 5 10 15Gly Ser Arg Gly Arg Pro Pro Arg Asn Met Gln Pro Thr Gly Arg Glu20 25 30Gly Ser Arg Ala Leu Ser Arg Arg Tyr Leu Arg Arg Leu Leu Leu Leu35 40 45Leu Leu Leu Leu Leu Leu Arg Gln Pro Val Thr Arg Ala Glu Thr Thr50 55 60Pro Gly Ala Pro Arg Ala Leu Ser Thr Leu Gly Ser Pro Ser Leu Phe65 70 75 80Thr Thr Pro Gly Val Pro Ser Ala Leu Thr Thr Pro Gly Leu Thr Thr85 90 95Pro Gly Thr Pro Lys Thr Leu Asp Leu Arg Gly Arg Ala Gln Ala Leu100 105 110Met Arg Ser Phe Pro Leu Val Asp Gly Tyr Val Gly Leu Asn Ser Ser115 120 125Gln Lys Leu Ala Cys Leu Ile Gly Val Glu Gly Gly His Ser Leu Asp130 135 140Ser Ser Leu Ser Val Leu Arg Ser Phe Tyr Val Leu Gly Val Arg Tyr145 150 155 160Leu Thr Leu Thr Phe Thr Cys Ser Thr Pro Trp Ala Glu Ser Ser Thr165 170 175Lys Phe Arg His His Met Tyr Thr Asn Val Ser Gly Leu Thr Ser Phe180 185 190Gly Glu Lys Val Val Glu Glu Leu Asn Arg Leu Gly Met Met Ile Asp195 200 205Leu Ser Tyr Ala Ser Asp Thr Leu Ile Arg Arg Val Leu Glu Val Ser210 215 220Gln Ala Pro Val Ile Phe Ser His Ser Ala Ala Arg Ala Val Cys Asp225 230 235 240Asn Leu Leu Asn Val Pro Asp Asp Ile Leu Gln Leu Leu Lys Lys Asn245 250 255Gly Gly Ile Val Met Val Thr Leu Ser Met Gly Val Leu Gln Cys Asn260 265 270Leu Leu Ala Asn Val Ser Thr Val Ala Asp Asp Ser Asn Arg Cys Ser275 280 285Val Pro Val Ile Gly Ser Glu Phe Ile Gly Ile Gly Gly Asn Tyr Asp290 295 300Gly Thr Gly Arg Phe Pro Gln Gly Leu Glu Asp Val Ser Thr Tyr Pro305 310 315 320Val Leu Ile Glu Glu Leu Leu Ser Arg Ser Trp Ser Glu Glu Glu Leu325 330 335Gln Gly Val Leu Arg Gly Asn Leu Leu Arg Val Phe Arg Gln Val Glu340 345 350Lys Val Arg Glu Glu Ser Arg Ala Gln Ser Pro Val Glu Ala Glu Phe355 360 365Pro Tyr Gly Gln Leu Ser Thr Ser Cys His Ser His Leu Val Pro Gln370 375 380Asn Gly His Gln Ala Thr His Leu Glu Val Thr Lys Gln Pro Thr Asn385 390 395 400Arg Val Pro Trp Arg Ser Ser Asn Ala Ser Pro Tyr Leu Val Pro Gly405 410 415Leu Val Ala Ala Ala Thr Ile Pro Thr Phe Thr Gln Trp Leu Cys420 425 430<210>52<211>480<212>PRT<213>人(Homo sapiens)<400>52Met Gln Pro Ser Gly Leu Glu Gly Pro Gly Thr Phe Gly Arg Trp Pro1 5 10 15Leu Leu Ser Leu Leu Leu Leu Leu Leu Leu Leu Gln Pro Val Thr Cys20 25 30Ala Tyr Thr Thr Pro Gly Pro Pro Arg Ala Leu Thr Thr Leu Gly Ala35 40 45Pro Arg Ala His Thr Met Pro Gly Thr Tyr Ala Pro Ser Thr Thr Leu50 55 60Ser Ser Pro Ser Thr Gln Gly Leu Gln Glu Gln Ala Arg Ala Leu Met65 70 75 80Arg Asp Phe Pro Leu Val Asp Gly His Asn Asp Leu Pro Leu Val Leu85 90 95Arg Gln Val Tyr Gln Lys Gly Leu Gln Asp Val Asn Leu Arg Asn Phe100 105 110Ser Tyr Gly Gln Thr Ser Leu Asp Arg Leu Arg Asp Gly Leu Val Gly115 120 125Ala Gln Phe Trp Ser Ala Tyr Val Pro Cys Gln Thr Gln Asp Arg Asp130 135 140Ala Leu Arg Leu Thr Leu Glu Gln Ile Asp Leu Ile Arg Arg Met Cys145 150 155 160Ala Ser Tyr Ser Glu Leu Glu Leu Val Thr Ser Ala Lys Gly Leu Asn165 170 175Ser Ser Gln Lys Leu Ala Cys Leu Ile Gly Val Glu Gly Gly His Ser180 185 190Leu Asp Ser Ser Leu Ser Val Leu Arg Ser Phe Tyr Val Leu Gly Val195 200 205Arg Tyr Leu Thr Leu Thr Phe Thr Cys Ser Thr Pro Trp Ala Glu Ser210 215 220Ser Thr Lys Phe Arg His His Met Tyr Thr Asn Val Ser Gly Leu Thr225 230 235 240Ser Phe Gly Glu Lys Val Val Glu Glu Leu Asn Arg Leu Gly Met Met245 250 255Ile Asp Leu Ser Tyr Ala Ser Asp Thr Leu Ile Arg Arg Val Leu Glu260 265 270Val Ser Gln Ala Pro Val Ile Phe Ser His Ser Ala Ala Arg Ala Val275 280 285Cys Asp Asn Leu Leu Asn Val Pro Asp Asp Ile Leu Gln Leu Leu Lys290 295 300Lys Asn Gly Gly Ile Val Met Val Thr Leu Ser Met Gly Val Leu Gln305 310 315 320Cys Asn Leu Leu Ala Asn Val Ser Thr Val Ala Asp His Phe Asp His325 330 335Ile Arg Ala Val Ile Gly Ser Glu Phe Ile Gly Ile Gly Gly Asn Tyr340 345 350Asp Gly Thr Gly Arg Phe Pro Gln Gly Leu Glu Asp Val Ser Thr Tyr355 360 365Pro Val Leu Ile Glu Glu Leu Leu Ser Arg Ser Trp Ser Glu Glu Glu370 375 380Leu Gln Gly Val Leu Arg Gly Asn Leu Leu Arg Val Phe Arg Gln Val385 390 395 400Glu Lys Val Arg Glu Glu Ser Arg Ala Gln Ser Pro Val Glu Ala Glu405 410 415Phe Pro Tyr Gly Gln Leu Ser Thr Ser Cys His Ser His Leu Val Pro420 425 430Gln Asn Gly His Gln Ala Thr His Leu Glu Val Thr Lys Gln Pro Thr435 440 445Asn Arg Val Pro Trp Arg Ser Ser Asn Ala Ser Pro Tyr Leu Val Pro450 455 460Gly Leu Val Ala Ala Ala Thr Ile Pro Thr Phe Thr Gln Trp Leu Cys465 470 475 480<210>53<211>371<212>PRT<213>人(Homo sapiens)<400>53Met Asp Ala Ala Thr Ala Pro Lys Gln Ala Trp Pro Pro Trp Pro Pro1 5 10 15Leu Leu Phe Leu Leu Leu Leu Pro Gly Gly Ser Gly Gly Ser Cys Pro20 25 30Ala Val Cys Asp Cys Thr Ser Gln Pro Gln Ala Val Leu Cys Gly His35 40 45Arg Gln Leu Glu Ala Val Pro Gly Gly Leu Pro Leu Asp Thr Glu Leu50 55 60Leu Asp Leu Ser Gly Asn Arg Leu Pro Lys Ala Gln Pro Leu Val Arg65 70 75 80Leu Gln Glu Leu Arg Leu Ser Gly Ala Cys Leu Thr Ser Ile Ala Ala85 90 95His Ala Phe His Gly Leu Thr Ala Phe His Leu Leu Asp Val Ala Asp100 105 110Asn Ala Leu Gln Thr Leu Glu Glu Thr Ala Phe Pro Ser Pro Asp Lys115 120 125Leu Val Thr Leu Arg Leu Ser Gly Asn Pro Leu Thr Cys Asp Cys Arg130 135 140Leu Leu Trp Leu Leu Arg Leu Arg His Leu Asp Phe Gly Met Ser Pro145 150 155 160Pro Ala Cys Ala Gly Pro His His Val Gln Gly Lys Ser Leu Lys Glu165 170 175Phe Ser Asp Ile Leu Pro Pro Gly His Phe Thr Cys Lys Pro Ala Leu180 185 190Ile Arg Lys Ser Gly Pro Arg Trp Val Ile Ala Glu Glu Gly Gly His195 200 205Ala Val Phe Ser Cys Ser Gly Asp Gly Asp Pro Ala Pro Thr Val Ser210 215 220Trp Met Arg Pro His Gly Ala Trp Leu Gly Arg Ala Gly Arg Val Arg225 230 235 240Val Leu Glu Asp Gly Thr Leu Glu Ile Arg Ser Val Gln Leu Arg Asp245 250 255Arg Gly Ala Tyr Val Cys Val Val Ser Asn Val Ala Gly Asn Asp Ser260 265 270Leu Arg Thr Trp Leu Glu Val Ile Gln Val Glu Pro Pro Asn Gly Thr275 280 285Leu Ser Asp Pro Asn Ile Thr Val Pro Gly Ile Pro Gly Pro Phe Phe290 295 300Leu Asp Ser Arg Gly Val Ala Met Val Leu Ala Val Gly Phe Leu Pro305 310 315 320Phe Leu Thr Ser Val Thr Leu Cys Phe Gly Leu Ile Ala Leu Trp Ser325 330 335Lys Gly Lys Gly Arg Val Lys His His Met Thr Phe Asp Phe Val Ala340 345 350Pro Arg Pro Ser Gly Asp Lys Asn Ser Gly Gly Asn Arg Val Thr Ala355 360 365Lys Leu Phe370<210>54<211>592<212>PRT<213>人(Homo sapiens)<400>54Met Asp Ala Ala Thr Ala Pro Lys Gln Ala Trp Pro Pro Trp Pro Pro1 5 10 15Leu Leu Phe Leu Leu Leu Leu Pro Gly Gly Ser Gly Gly Ser Cys Pro20 25 30Ala Val Cys Asp Cys Thr Ser Gln Pro Gln Ala Val Leu Cys Gly His35 40 45Arg Gln Leu Glu Ala Val Pro Gly Gly Leu Pro Leu Asp Thr Glu Leu50 55 60Leu Asp Leu Ser Gly Asn Arg Leu Trp Gly Leu Gln Gln Gly Met Leu65 70 75 80Ser Arg Leu Ser Leu Leu Gln Glu Leu Asp Leu Ser Tyr Asn Gln Leu85 90 95Ser Thr Leu Glu Pro Gly Ala Phe His Gly Leu Gln Ser Leu Leu Thr100 105 110Leu Arg Leu Gln Gly Asn Arg Leu Arg Ile Met Gly Pro Gly Val Phe115 120 125Ser Gly Leu Ser Ala Leu Thr Leu Leu Asp Leu Arg Leu Asn Gln Ile130 135 140Val Leu Phe Leu Asp Gly Ala Phe Gly Glu Leu Gly Ser Leu Gln Lys145 150 155 160Leu Glu Val Gly Asp Asn His Leu Val Phe Val Ala Pro Gly Ala Phe165 170 175Ala Gly Leu Ala Lys Leu Ser Thr Leu Thr Leu Glu Arg Cys Asn Leu180 185 190Ser Thr Val Pro Gly Leu Ala Leu Ala Arg Leu Pro Ala Leu Val Ala195 200 205Leu Arg Leu Arg Glu Leu Asp Ile Gly Arg Leu Pro Ala Gly Ala Leu210 215 220Arg Gly Leu Gly Gln Leu Lys Glu Leu Glu Ile Hi s Leu Trp Pro Ser225 230 235 240Leu Glu Ala Leu Asp Pro Gly Ser Leu Val Gly Leu Asn Leu Ser Ser245 250 255Leu Ala Ile Thr Arg Cys Asn Leu Ser Ser Val Pro Phe Gln Ala Leu260 265 270Tyr His Leu Ser Phe Leu Arg Val Leu Asp Leu Ser Gln Asn Pro Ile275 280 285Ser Ala Ile Pro Ala Arg Arg Leu Ser Pro Leu Val Arg Leu Gln Glu290 295 300Leu Arg Leu Ser Gly Ala Cys Leu Thr Ser Ile Ala Ala His Ala Phe305 310 315 320His Gly Leu Thr Ala Phe His Leu Leu Asp Val Ala Asp Asn Ala Leu325 330 335Gln Thr Leu Glu Glu Thr Ala Phe Pro Ser Pro Asp Lys Leu Val Thr340 345 350Leu Arg Leu Ser Gly Asn Pro Leu Thr Cys Asp Cys Arg Leu Leu Trp355 360 365Leu Leu Arg Leu Arg His Leu Asp Phe Gly Met Ser Pro Pro Ala Cys370 375 380Ala Gly Pro His His Val Gln Gly Lys Ser Leu Lys Glu Phe Ser Asp385 390 395 400Ile Leu Pro Pro Gly His Phe Thr Cys Lys Pro Ala Leu Ile Arg Lys405 410 415Ser Gly Pro Arg Trp Val Ile Ala Glu Glu Gly Gly His Ala Val Phe420 425 430Ser Cys Ser Gly Asp Gly Asp Pro Ala Pro Thr Val Ser Trp Met Arg435 440 445Pro His Gly Ala Trp Leu Gly Arg Ala Gly Arg Val Arg Val Leu Glu450 455 460Asp Gly Thr Leu Glu Ile Arg Ser Val Gln Leu Arg Asp Arg Gly Ala465 470 475 480Tyr Val Cys Val Val Ser Asn Val Ala Gly Asn Asp Ser Leu Arg Thr485 490 495Trp Leu Glu Val Ile Gln Val Glu Pro Pro Asn Gly Thr Leu Ser Asp500 505 510Pro Asn Ile Thr Val Pro Gly Ile Pro Gly Pro Phe Phe Leu Asp Ser5l5 520 525Arg Gly Val Ala Met Val Leu Ala Val Gly Phe Leu Pro Phe Leu Thr530 535 540Ser Val Thr Leu Cys Phe Gly Leu Ile Ala Leu Trp Ser Lys Gly Lys545 550 555 560Gly Arg Val Lys His His Met Thr Phe Asp Phe Val Ala Pro Arg Pro565 570 575Ser Gly Asp Lys Asn Ser Gly Gly Asn Arg Val Thr Ala Lys Leu Phe580 585 590<210>55<211>142<212>PRT<213>人(Homo sapiens)<400>55Met Ala Arg Tyr Met Leu Leu Leu Leu Leu Ala Val Trp Val Leu Thr1 5 10 15Gly Glu Leu Trp Pro Gly Ala Glu Ala Arg Ala Ala Pro Tyr Gly Val20 25 30Arg Leu Cys Gly Arg Glu Phe Ile Arg Ala Val Ile Phe Thr Cys Gly35 40 45Gly Ser Arg Trp Arg Arg Ser Asp Ile Leu Ala His Glu Ala Met Gly50 55 60Asp Thr Phe Pro Asp Ala Asp Ala Asp Glu Asp Ser Leu Ala Gly Glu65 70 75 80Leu Asp Glu Ala Met Gly Ser Ser Glu Trp Leu Ala Leu Thr Lys Ser85 90 95Pro Gln Ala Phe Tyr Arg Gly Arg Pro Ser Trp Gln Gly Thr Pro Gly100 105 110Val Leu Arg Gly Ser Arg Asp Val Leu Ala Gly Leu Ser Ser Ser Cys115 120 125Cys Lys Trp Gly Cys Ser Lys Ser Glu Ile Ser Ser Leu Cys130 135 140<210>56<211>230<212>PRT<213>人(Homo sapiens)<400>56Met Ser Glu Glu Val Thr Tyr Ala Thr Leu Thr Phe Gln Asp Ser Ala1 5 10 15Gly Ala Arg Asn Asn Arg Asp Gly Asn Asn Leu Arg Lys Arg Gly His20 25 30Pro Ala Pro Ser Pro Ile Trp Arg His Ala Ala Leu Gly Leu Val Thr35 40 45Leu Cys Leu Met Leu Leu Ile Gly Leu Val Thr Leu Gly Met Met Phe50 55 60Leu Gln Ile Ser Asn Asp Ile Asn Ser Asp Ser Glu Lys Leu Ser Gln65 70 75 80Leu Gln Lys Thr Ile Gln Gln Gln Gln Asp Asn Leu Ser Gln Gln Leu85 90 95Gly Asn Ser Asn Asn Leu Ser Met Glu Glu Glu Phe Leu Lys Ser Gln100 105 110Ile Ser Ser Leu Leu Lys Arg Gln Glu Gln Met Ala Ile Lys Leu Cys115 120 125Gln Glu Leu Ile Ile His Thr Ser Asp His Arg Cys Asn Pro Cys Pro130 135 140Lys Met Trp Gln Trp Tyr Gln Asn Ser Cys Tyr Tyr Phe Thr Thr Asn145 150 155 160Glu Glu Lys Thr Trp Ala Asn Ser Arg Lys Asp Cys Ile Asp Lys Asn165 170 175Ser Thr Leu Val Lys Ile Asp Ser Leu Glu Glu Lys Asp Phe Leu Met180 185 190Ser Gln Pro Leu Leu Met Phe Ser Phe Phe Trp Leu Gly Leu Ser Trp195 200 205Asp Ser Ser Gly Arg Ser Trp Phe Trp Glu Asp Gly Ser Val Pro Ser210 215 220Pro Ser Leu Tyr Val Ser225 230<210>57<211>194<212>PRT<213>人(Homo sapiens)<400>57Met Trp Leu Ser Pro Ala Leu Leu Leu Leu Ile Leu Pro Gly Tyr Ser1 5 10 15Ile Ala Ala Lys Ile Thr Gly Pro Thr Thr Val Asn Gly Ser Glu Gln20 25 30Gly Ser Leu Thr Val Gln Cys Ala Tyr Gly Ser Gly Trp Glu Thr Tyr35 40 45Leu Lys Trp Arg Cys Gln Gly Ala Asp Trp Asn Tyr Cys Asn Ile Leu50 55 60Val Lys Thr Asn Gly Ser Glu Gln Glu Val Lys Lys Asn Arg Val Ser65 70 75 80Ile Arg Asp Asn Gln Lys Asn His Met Phe Thr Val Thr Met Glu Asn85 90 95Leu Lys Arg Asp Asp Ala Asp Ser Tyr Trp Cys Gly Thr Glu Arg Pro100 105 110Gly Ile Asp Leu Gly Val Lys Val Gln Val Thr Ile Asn Pro Gly Thr115 120 125Gln Thr Ala Val Ser Glu Trp Thr Thr Thr Thr Ala Ser Leu Ala Phe130 135 140Thr Ala Ala Ala Thr Gln Lys Thr Ser Ser Pro Leu Thr Arg Ser Pro145 150 155 160Leu Lys Ser Thr His Phe Leu Phe Leu Phe Leu Leu Glu Leu Pro Leu165 170 175Leu Leu Ser Met Leu Gly Thr Val Leu Trp Val Asn Arg Pro Gln Arg180 185 190Arg Ser<210>58<211>333<212>PRT<213>人(Homo sapiens)<400>58Met Arg Ile Trp Trp Leu Leu Leu Ala Ile Glu Ile Cys Thr Gly Asn1 5 10 15Ile Asn Ser Gln Asp Thr Cys Arg Gln Gly His Pro Gly Ile Pro Gly20 25 30Asn Pro Gly His Asn Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Ala35 40 45Lys Gly Asp Lys Gly Asp Ala Gly Glu Pro Gly Arg Pro Gly Ser Pro50 55 60Gly Lys Asp Gly Thr Ser Gly Glu Lys Gly Glu Arg Gly Ala Asp Gly65 70 75 80Lys Val Glu Ala Lys Gly Ile Lys Gly Asp Gln Gly Ser Arg Gly Ser85 90 95Pro Gly Lys His Gly Pro Lys Gly Leu Ala Gly Pro Met Gly Glu Lys100 105 110Gly Leu Arg Gly Glu Thr Gly Pro Gln Gly Gln Lys Gly Asn Lys Gly115 120 125Asp Val Gly Pro Thr Gly Pro Glu Gly Pro Arg Gly Asn Ile Gly Pro130 135 140Leu Gly Pro Thr Gly Leu Pro Gly Pro Met Gly Pro Ile Gly Lys Pro145 150 155 160Gly Pro Lys Gly Glu Ala Gly Pro Thr Gly Pro Gln Gly Glu Pro Gly165 170 175Val Arg Gly Ile Arg Gly Trp Lys Gly Asp Arg Gly Glu Lys Gly Lys180 185 190Ile Gly Glu Thr Leu Val Leu Pro Lys Ser Ala Phe Thr Val Gly Leu195 200 205Thr Val Leu Ser Lys Phe Pro Ser Ser Asp Met Pro Ile Lys Phe Asp210 215 220Lys Ile Leu Tyr Asn Glu Phe Asn His Tyr Asp Thr Ala Ala Gly Lys225 230 235 240Phe Thr Cys His Ile Ala Gly Val Tyr Tyr Phe Thr Tyr His Ile Thr245 250 255Val Phe Ser Arg Asn Val Gln Val Ser Leu Val Lys Asn Gly Val Lys260 265 270Ile Leu His Thr Lys Asp Ala Tyr Met Ser Ser Glu Asp Gln Ala Ser275 280 285Gly Gly Ile Val Leu Gln Leu Lys Leu Gly Asp Glu Val Trp Leu Gln290 295 300Val Thr Gly Gly Glu Arg Phe Asn Gly Leu Phe Ala Asp Glu Asp Asp305 310 315 320Asp Thr Thr Phe Thr Gly Phe Leu Leu Phe Ser Ser Pro325 330<210>59<211>225<212>PRT<213>人(Homo sapiens)<400>59Met Arg Ile Trp Trp Leu Leu Leu Ala Ile Glu Ile Cys Thr Gly Asn1 5 10 15Ile Asn Ser Gln Asp Thr Cys Arg Gln Gly His Pro Gly Ile Pro Gly20 25 30Asn Pro Gly His Asn Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Ala35 40 45Lys Gly Asp Lys Gly Asp Ala Gly Glu Ala Gly Pro Thr Gly Pro Gln50 55 60Gly Glu Pro Gly Val Arg Gly Ile Arg Gly Trp Lys Gly Asp Arg Gly65 70 75 80Glu Lys Gly Lys Ile Gly Glu Thr Leu Val Leu Pro Lys Ser Ala Phe85 90 95Thr Val Gly Leu Thr Val Leu Ser Lys Phe Pro Ser Ser Asp Met Pro100 105 110Ile Lys Phe Asp Lys Ile Leu Tyr Asn Glu Phe Asn His Tyr Asp Thr115 120 125Ala Ala Gly Lys Phe Thr Cys His Ile Ala Gly Val Tyr Tyr Phe Thr130 135 140Tyr His Ile Thr Val Phe Ser Arg Asn Val Gln Val Ser Leu Val Lys145 150 155 160Asn Gly Val Lys Ile Leu His Thr Lys Asp Ala Tyr Met Ser Ser Glu165 170 175Asp Gln Ala Ser Gly Gly Ile Val Leu Gln Leu Lys Leu Gly Asp Glu180 185 190Val Trp Leu Gln Val Thr Gly Gly Glu Arg Phe Asn Gly Leu Phe Ala195 200 205Asp Glu Asp Asp Asp Thr Thr Phe Thr Gly Phe Leu Leu Phe Ser Ser210 215 220Pro225<210>60<211>205<212>PRT<213>人(Homo sapiens)<400>60Met Met Arg Thr Leu Ile Thr Thr His Pro Leu Pro Leu Leu Leu Leu1 5 10 15Pro Gln Gln Leu Leu Gln Leu Val Gln Phe Gln Glu Val Asp Thr Asp20 25 30Phe Asp Phe Pro Glu Glu Asp Lys Lys Glu Glu Phe Glu Glu Cys Leu35 40 45Glu Lys Phe Phe Ser Thr Gly Pro Ala Arg Pro Pro Thr Lys Glu Lys50 55 60Val Lys Arg Arg Val Leu Ile Glu Pro Gly Met Pro Leu Asn His Ile65 70 75 80Glu Tyr Cys Asn His Glu Ile Met Gly Lys Asn Val Tyr Tyr Lys His85 90 95Arg Trp Val Ala Glu His Tyr Phe Leu Leu Met Gln Tyr Asp Glu Leu100 105 110Gln Lys Ile Cys Tyr Asn Arg Phe Val Pro Cys Lys Asn Gly Ile Arg115 120 125Lys Cys Asn Arg Ser Lys Gly Leu Val Glu Gly Val Tyr Cys Asn Leu130 135 140Thr Glu Ala Phe Glu Ile Pro Ala Cys Lys Tyr Glu Ser Leu Tyr Arg145 150 155 160Lys Gly Tyr Val Leu Ile Thr Cys Ser Trp Gln Asn Glu Met Gln Lys165 170 175Arg Ile Pro His Thr Ile Asn Asp Leu Val Glu Pro Pro Glu His Arg180 185 190Ser Phe Leu Ser Glu Asp Gly Val Phe Val Ile Ser Pro195 200 205<210>61<211>95<212>PRT<213>人(Homo sapiens)<400>61Met Glu Val Val Leu Ile Phe Leu Cys Ser Leu Leu Ala His Ile Val1 5 10 15Leu Ala Asp Ala Val Glu Arg Glu Lys Gln Ile Asp Pro Phe His Tyr20 25 30Asp Tyr Gln Thr Leu Arg Ile Arg Gly Leu Val Cys Ala Val Val Leu35 40 45Phe Ser Ile Gly Ile Leu Leu Ile Leu Gly Cys Arg Cys Lys Cys Ser50 55 60Phe Asn Gln Lys Pro Arg Thr Pro Gly Glu Glu Glu Ala Gln Val Glu65 70 75 80Asn Leu Ile Thr Ala Asn Ala Thr Lys Leu Gln Lys Ala Glu Ser85 90 95<210>62<211>595<212>PRT<213>人(Homo sapiens)<400>62Met Glu Val Gly Met Gly Cys Trp Ala Arg Glu Val Leu Val Pro Glu1 5 10 15Gly Pro Leu Tyr Arg Val Ala Gly Thr Ala Val Ser Ile Ser Cys Asn20 25 30Val Thr Gly Tyr Glu Gly Pro Ala Gln Gln Asn Phe Glu Trp Phe Leu35 40 45Tyr Arg Pro Glu Ala Pro Asp Thr Ala Leu Gly Ile Val Ser Thr Lys50 55 60Asp Thr Gln Phe Ser Tyr Ala Val Phe Lys Ser Arg Val Val Ala Gly65 70 75 80Glu Val Gln Val Gln Arg Leu Gln Gly Asp Ala Val Val Leu Lys Ile85 90 95Ala Arg Leu Gln Ala Gln Asp Ala Gly Ile Tyr Glu Cys His Thr Pro100 105 110Ser Thr Asp Thr Arg Tyr Leu Gly Ser Tyr Ser Gly Lys Val Glu Leu115 120 125Arg Val Leu Pro Asp Val Leu Gln Val Ser Ala Ala Pro Pro Gly Pro130 135 140Arg Gly Arg Gln Ala Pro Thr Ser Pro Pro Arg Met Thr Val His Glu145 150 155 160Gly Gln Glu Leu Ala Leu Gly Cys Leu Ala Arg Thr Ser Thr Gln Lys165 170 175His Thr His Leu Ala Val Ser Phe Gly Arg Ser Val Pro Glu Ala Pro180 185 190Val Gly Arg Ser Thr Leu Gln Glu Val Val Gly Ile Arg Ser Asp Leu195 200 205Ala Val Glu Ala Gly Ala Pro Tyr Ala Glu Arg Leu Ala Ala Gly Glu210 215 220Leu Arg Leu Gly Lys Glu Gly Thr Asp Arg Tyr Arg Met Val Val Gly225 230 235 240Gly Ala Gln Ala Gly Asp Ala Gly Thr Tyr His Cys Thr Ala Ala Glu245 250 255Trp Ile Gln Asp Pro Asp Gly Ser Trp Ala Gln Ile Ala Glu Lys Arg260 265 270Ala Val Leu Ala His Val Asp Val Gln Thr Leu Ser Ser Gln Leu Ala275 280 285Val Thr Val Gly Pro Gly Glu Arg Arg Ile Gly Pro Gly Glu Pro Leu290 295 300Glu Leu Leu Cys Asn Val Ser Gly Ala Leu Pro Pro Ala Gly Arg His305 310 315 320Ala Ala Tyr Ser Val Gly Trp Glu Met Ala Pro Ala Gly His Leu Gly325 330 335Pro Gly Arg Leu Val Ala Gln Leu Asp Thr Glu Gly Val Gly Ser Leu340 345 350Gly Pro Gly Tyr Glu Gly Arg His Ile Ala Met Glu Lys Val Ala Ser355 360 365Arg Thr Tyr Arg Leu Arg Leu Glu Ala Ala Arg Pro Gly Asp Ala Gly370 375 380Thr Tyr Arg Cys Leu Ala Lys Ala Tyr Val Arg Gly Ser Gly Thr Arg385 390 395 400Leu Arg Glu Ala Ala Ser Ala Arg Ser Arg Pro Leu Pro Val His Val405 410 415Arg Glu Glu Gly Val Val Leu Glu Ala Val Ala Trp Leu Ala Gly Gly420 425 430Thr Val Tyr Arg Gly Glu Thr Ala Ser Leu Leu Cys Asn Ile Ser Val435 440 445Arg Gly Gly Pro Pro Gly Leu Arg Leu Ala Ala Ser Trp Trp Val Glu450 455 460Arg Pro Glu Asp Gly Glu Leu Ser Ser Val Pro Ala Gln Leu Val Gly465 470 475 480Gly Val Gly Gln Asp Gly Val Ala Glu Leu Gly Val Arg Pro Gly Gly485 490 495Gly Pro Val Ser Val Glu Leu Val Gly Pro Arg Ser His Arg Leu Arg500 505 510Leu His Ser Leu Gly Pro Glu Asp Glu Gly Val Tyr His Cys Ala Pro515 520 525Ser Ala Trp Val Gln His Ala Asp Tyr Ser Trp Tyr Gln Ala Gly Ser530 535 540Ala Arg Ser Gly Pro Val Thr Val Tyr Pro Tyr Met His Ala Leu Asp545 550 555 560Thr Leu Phe Val Pro Leu Leu Val Gly Thr Gly Val Ala Leu Val Thr565 570 575Gly Ala Thr Val Leu Gly Thr Ile Thr Cys Cys Phe Met Lys Arg Leu580 585 590Arg Lys Arg595<210>63<211>613<212>PRT<213>人(Homo sapiens)<400>63Met Gly Ala Leu Arg Pro Thr Leu Leu Pro Pro Ser Leu Pro Leu Leu1 5 10 15Leu Leu Leu Met Leu Gly Met Gly Cys Trp Ala Arg Glu Val Leu Val20 25 30Pro Glu Gly Pro Leu Tyr Arg Val Ala Gly Thr Ala Val Ser Ile Ser35 40 45Cys Asn Val Thr Gly Tyr Glu Gly Pro Ala Gln Gln Asn Phe Glu Trp50 55 60Phe Leu Tyr Arg Pro Glu Ala Pro Asp Thr Ala Leu Gly Ile Val Ser65 70 75 80Thr Lys Asp Thr Gln Phe Ser Tyr Ala Val Phe Lys Ser Arg Val Val85 90 95Ala Gly Glu Val Gln Val Gln Arg Leu Gln Gly Asp Ala Val Val Leu100 105 110Lys Ile Ala Arg Leu Gln Ala Gln Asp Ala Gly Ile Tyr Glu Cys His115 120 125Thr Pro Ser Thr Asp Thr Arg Tyr Leu Gly Ser Tyr Ser Gly Lys Val130 135 140Glu Leu Arg Val Leu Pro Asp Val Leu Gln Val Ser Ala Ala Pro Pro145 150 155 160Gly Pro Arg Gly Arg Gln Ala Pro Thr Ser Pro Pro Arg Met Thr Val165 170 175His Glu Gly Gln Glu Leu Ala Leu Gly Cys Leu Ala Arg Thr Ser Thr180 185 190Gln Lys His Thr His Leu Ala Val Ser Phe Gly Arg Ser Val Pro Glu195 200 205Ala Pro Val Gly Arg Ser Thr Leu Gln Glu Val Val Gly Ile Arg Ser210 215 220Asp Leu Ala Val Glu Ala Gly Ala Pro Tyr Ala Glu Arg Leu Ala Ala225 230 235 240Gly Glu Leu Arg Leu Gly Lys Glu Gly Thr Asp Arg Tyr Arg Met Val245 250 255Val Gly Gly Ala Gln Ala Gly Asp Ala Gly Thr Tyr His Cys Thr Ala260 265 270Ala Glu Trp Ile Gln Asp Pro Asp Gly Ser Trp Ala Gln Ile Ala Glu275 280 285Lys Arg Ala Val Leu Ala His Val Asp Val Gln Thr Leu Ser Ser Gln290 295 300Leu Ala Val Thr Val Gly Pro Gly Glu Arg Arg Ile Gly Pro Gly Glu305 310 315 320Pro Leu Glu Leu Leu Cys Asn Val Ser Gly Ala Leu Pro Pro Ala Gly325 330 335Arg His Ala Ala Tyr Ser Val Gly Trp Glu Met Ala Pro Ala Gly Ala340 345 350Pro Gly Pro Gly Arg Leu Val Ala Gln Leu Asp Thr Glu Gly Val Gly355 360 365Ser Leu Gly Pro Gly Tyr Glu Gly Arg His Ile Ala Met Glu Lys Val370 375 380Ala Ser Arg Thr Tyr Arg Leu Arg Leu Glu Ala Ala Arg Pro Gly Asp385 390 395 400Ala Gly Thr Tyr Arg Cys Leu Ala Lys Ala Tyr Val Arg Gly Ser Gly405 410 415Thr Arg Leu Arg Glu Ala Ala Ser Ala Arg Ser Arg Pro Leu Pro Val420 425 430His Val Arg Glu Glu Gly Val Val Leu Glu Ala Val Ala Trp Leu Ala435 440 445Gly Gly Thr Val Tyr Arg Gly Glu Thr Ala Ser Leu Leu Cys Asn Ile450 455 460Ser Val Arg Gly Gly Pro Pro Gly Leu Arg Leu Ala Ala Ser Trp Trp465 470 475 480Val Glu Arg Pro Glu Asp Gly Glu Leu Ser Ser Val Pro Ala Gln Leu485 490 495Val Gly Gly Val Gly Gln Asp Gly Val Ala Glu Leu Gly Val Arg Pro500 505 510Gly Gly Gly Pro Val Ser Val Glu Leu Val Gly Pro Arg Ser His Arg515 520 525Leu Arg Leu His Ser Leu Gly Pro Glu Asp Glu Gly Val Tyr His Cys530 535 540Ala Pro Ser Ala Trp Val Gln His Ala Asp Tyr Ser Trp Tyr Gln Ala545 550 555 560Gly Ser Ala Arg Ser Gly Pro Val Thr Val Tyr Pro Tyr Met His Ala565 570 575Leu Asp Thr Leu Phe Val Pro Leu Leu Val Gly Thr Gly Val Ala Leu580 585 590Val Thr Gly Ala Thr Val Leu Gly Thr Ile Thr Cys Cys Phe Met Lys595 600 605Arg Leu Arg Lys Arg610<210>64<211>596<212>PRT<213>人(Homo sapiens)<400>64Met Ala Ala Asn Ser Thr Ser Asp Leu His Thr Pro Gly Thr Gln Leu1 5 10 15Ser Val Ala Asp Ile Ile Val Ile Thr Val Tyr Phe Ala Leu Asn Val20 25 30Ala Val Gly Ile Trp Ser Ser Cys Arg Ala Ser Arg Asn Thr Val Asn35 40 45Gly Tyr Phe Leu Ala Gly Arg Asp Met Thr Trp Trp Pro Ile Gly Ala50 55 60Ser Leu Phe Ala Ser Ser Glu Gly Ser Gly Leu Phe Ile Gly Leu Ala65 70 75 80Gly Ser Gly Ala Ala Gly Gly Leu Ala Val Ala Gly Phe Glu Trp Asn85 90 95Ala Thr Tyr Val Leu Leu Ala Leu Ala Trp Val Phe Val Pro Ile Tyr100 105 110Ile Ser Ser Glu Ile Val Thr Leu Pro Glu Tyr Ile Gln Lys Arg Tyr115 120 125Gly Gly Gln Arg Ile Arg Met Tyr Leu Ser Val Leu Ser Leu Leu Leu130 135 140Ser Val Phe Thr Lys Ile Ser Leu Asp Leu Tyr Ala Gly Ala Leu Phe145 150 155 160Val His Ile Cys Leu Gly Trp Asn Phe Tyr Leu Ser Thr Ile Leu Thr165 170 175Leu Gly Ile Thr Ala Leu Tyr Thr Ile Ala Gly Gly Leu Ala Ala Val180 185 190Ile Tyr Thr Asp Ala Leu Gln Thr Leu Ile Met Val Val Gly Ala Val195 200 205Ile Leu Thr Ile Lys Ala Phe Asp Gln Ile Gly Gly Tyr Gly Gln Leu210 215 220Glu Ala Ala Tyr Ala Gln Ala Ile Pro Ser Arg Thr Ile Ala Asn Thr225 230 235 240Thr Cys His Leu Pro Arg Thr Asp Ala Met His Met Phe Arg Asp Pro245 250 255His Thr Gly Asp Leu Pro Trp Thr Gly Met Thr Phe Gly Leu Thr Ile260 265 270Met Ala Thr Trp Tyr Trp Cys Thr Asp Gln Val Ile Val Gln Arg Ser275 280 285Leu Ser Ala Arg Asp Leu Asn His Ala Lys Ala Gly Ser Ile Leu Ala290 295 300Ser Tyr Leu Lys Met Leu Pro Met Gly Leu Ile Ile Met Pro Gly Met305 310 315 320Ile Ser Arg Ala Leu Phe Pro Asp Asp Val Gly Cys Val Val Pro Ser325 330 335Glu Cys Leu Arg Ala Cys Gly Ala Glu Val Gly Cys Ser Asn Ile Ala340 345 350Tyr Pro Lys Leu Val Met Glu Leu Met Pro Ile Gly Leu Arg Gly Leu355 360 365Met Ile Ala Val Met Leu Ala Ala Leu Met Ser Ser Leu Thr Ser Ile370 375 380Phe Asn Ser Ser Ser Thr Leu Phe Thr Met Asp Ile Trp Arg Arg Leu385 390 395 400Arg Pro Arg Ser Gly Glu Arg Glu Leu Leu Leu Val Gly Arg Leu Val405 410 415Ile Val Ala Leu Ile Gly Val Ser Val Ala Trp Ile Pro Val Leu Gln420 425 430Asp Ser Asn Ser Gly Gln Leu Phe Ile Tyr Met Gln Ser Val Thr Ser435 440 445Ser Leu Ala Pro Pro Val Thr Ala Val Phe Val Leu Gly Val Phe Trp450 455 460Arg Arg Ala Asn Glu Gln Gly Ala Phe Trp Gly Leu Ile Ala Gly Leu465 470 475 480Val Val Gly Ala Thr Arg Leu Val Leu Glu Phe Leu Asn Pro Ala Pro485 490 495Pro Cys Gly Glu Pro Asp Thr Arg Pro Ala Val Leu Gly Ser Ile His500 505 510Tyr Leu His Phe Ala Val Ala Leu Phe Ala Leu Ser Gly Ala Val Val515 520 525Val Ala Gly Ser Leu Leu Thr Pro Pro Pro Gln Ser Val Gln Ile Glu530 535 540Asn Leu Thr Trp Trp Thr Leu Ala Gln Asp Val Pro Leu Gly Thr Lys545 550 555 560Ala Gly Asp Gly Gln Thr Pro Gln Lys His Ala Phe Trp Ala Arg Val565 570 575Cys Gly Phe Asn Ala Ile Leu Leu Met Cys Val Asn Ile Phe Phe Tyr580 585 590Ala Tyr Phe Ala595<210>65<211>393<212>PRT<213>人(Homo sapiens)<400>65Met Asp Ser Leu Lys Asn Glu Asn Tyr Asp Leu Val Phe Val Glu Ala1 5 10 15Phe Asp Phe Cys Ser Phe Leu Ile Ala Glu Lys Leu Val Lys Pro Phe20 25 30Val Ala Ile Leu Pro Thr Thr Phe Gly Ser Leu Asp Phe Gly Leu Pro35 40 45Ser Pro Leu Ser Tyr Val Pro Val Phe Pro Ser Leu Leu Thr Asp His50 55 60Met Asp Phe Trp Gly Arg Val Lys Asn Phe Leu Met Phe Phe Ser Phe65 70 75 80Ser Arg Ser Gln Trp Asp Met Gln Ser Thr Phe Asp Asn Thr Ile Lys85 90 95Glu His Phe Pro Glu Gly Ser Arg Pro Val Leu Ser His Leu Leu Leu100 105 110Lys Ala Glu Leu Trp Phe Val Asn Ser Asp Phe Ala Phe Asp Phe Ala115 120 125Arg Pro Leu Leu Pro Asn Thr Val Tyr Ile Gly Gly Leu Met Glu Lys130 135 140Pro Ile Lys Pro Val Pro Gln Asp Leu Asp Asn Phe Ile Ala Asn Phe145 150 155 160Gly Asp Ala Gly Phe Val Leu Val Ala Phe Gly Ser Met Leu Asn Thr165 170 175His Gln Ser Gln Glu Val Leu Lys Lys Met His Asn Ala Phe Ala His180 185 190Leu Pro Gln Gly Val Ile Trp Thr Cys Gln Ser Ser His Trp Pro Arg195 200 205Asp Val His Leu Ala Thr Asn Val Lys Ile Val Asp Trp Leu Pro Gln210 215 220Ser Asp Leu Leu Ala His Pro Ser Ile Arg Leu Phe Val Thr His Gly225 230 235 240Gly Gln Asn Ser Val Met Glu Ala Ile Arg His Gly Val Pro Met Val245 250 255Gly Leu Pro Val Asn Gly Asp Gln His Gly Asn Met Val Arg Val Val260 265 270Ala Lys Asn Tyr Gly Val Ser Ile Arg Leu Asn Gln Val Thr Ala Asp275 280 285Thr Leu Thr Leu Thr Met Lys Gln Val Ile Glu Asp Lys Arg Tyr Lys290 295 300Ser Ala Val Val Ala Ala Ser Val Ile Leu His Ser Gln Pro Leu Ser305 310 315 320Pro Ala Gln Arg Leu Val Gly Trp Ile Asp His Ile Leu Gln Thr Gly325 330 335Gly Ala Thr His Leu Lys Pro Tyr Ala Phe Gln Gln Pro Trp His Glu340 345 350Gln Tyr Leu Ile Asp Val Phe Val Phe Leu Leu Gly Leu Thr Leu Gly355 360 365Thr Met Trp Leu Cys Gly Lys Leu Leu Gly Val Val Ala Arg Trp Leu370 375 380Arg Gly Ala Arg Lys Val Lys Lys Thr385 390<210>66<211>523<212>PRT<213>人(Homo sapiens)<400>66Met Val Gly Gln Arg Val Leu Leu Leu Val Ala Phe Leu Leu Ser Gly1 5 10 15Val Leu Leu Ser Glu Ala Ala Lys Ile Leu Thr Ile Ser Thr Leu Gly20 25 30Gly Ser His Tyr Leu Leu Leu Asp Arg Val Ser Gln Ile Leu Gln Glu35 40 45His Gly His Asn Val Thr Met Leu His Gln Ser Gly Lys Phe Leu Ile50 55 60Pro Asp Ile Lys Glu Glu Glu Lys Ser Tyr Gln Val Ile Arg Trp Phe65 70 75 80Ser Pro Glu Asp His Gln Lys Arg Ile Lys Lys His Phe Asp Ser Tyr85 90 95Ile Glu Thr Ala Leu Asp Gly Arg Lys Glu Ser Glu Ala Leu Val Lys100 105 110Leu Met Glu Ile Phe Gly Thr Gln Cys Ser Tyr Leu Leu Ser Arg Lys115 120 125Asp Ile Met Asp Ser Leu Lys Asn Glu Asn Tyr Asp Leu Val Phe Val130 135 140Glu Ala Phe Asp Phe Cys Ser Phe Leu Ile Ala Glu Lys Leu Val Lys145 150 155 160Pro Phe Val Ala Ile Leu Pro Thr Thr Phe Gly Ser Leu Asp Phe Gly165 170 175Leu Pro Ser Pro Leu Ser Tyr Val Pro Val Phe Pro Ser Leu Leu Thr180 185 190Asp His Met Asp Phe Trp Gly Arg Val Lys Asn Phe Leu Met Phe Phe195 200 205Ser Phe Ser Arg Ser Gln Trp Asp Met Gln Ser Thr Phe Asp Asn Thr210 215 220Ile Lys Glu His Phe Pro Glu Gly Ser Arg Pro Val Leu Ser His Leu225 230 235 240Leu Leu Lys Ala Glu Leu Trp Phe Val Asn Ser Asp Phe Ala Phe Asp245 250 255Phe Ala Arg Pro Leu Leu Pro Asn Thr Val Tyr Ile Gly Gly Leu Met260 265 270Glu Lys Pro Ile Lys Pro Val Pro Gln Asp Leu Asp Asn Phe Ile Ala275 280 285Asn Phe Gly Asp Ala Gly Phe Val Leu Val Ala Phe Gly Ser Met Leu290 295 300Asn Thr His Gln Ser Gln Glu Val Leu Lys Lys Met His Asn Ala Phe305 310 315 320Ala His Leu Pro Gln Gly Val Ile Trp Thr Cys Gln Ser Ser His Trp325 330 335Pro Arg Asp Val His Leu Ala Thr Asn Val Lys Ile Val Asp Trp Leu340 345 350Pro Gln Ser Asp Leu Leu Ala His Pro Ser Ile Arg Leu Phe Val Thr355 360 365His Gly Gly Gln Asn Ser Val Met Glu Ala Ile Arg His Gly Val Pro370 375 380Met Val Gly Leu Pro Val Asn Gly Asp Gln His Gly Asn Met Val Arg385 390 395 400Val Val Ala Lys Asn Tyr Gly Val Ser Ile Arg Leu Asn Gln Val Thr405 410 415Ala Asp Thr Leu Thr Leu Thr Met Lys Gln Val Ile Glu Asp Lys Arg420 425 430Tyr Lys Ser Ala Val Val Ala Ala Ser Val Ile Leu His Ser Gln Pro435 440 445Leu Ser Pro Ala Gln Arg Leu Val Gly Trp Ile Asp His Ile Leu Gln450 455 460Thr Gly Gly Ala Thr His Leu Lys Pro Tyr Ala Phe Gln Gln Pro Trp465 470 475 480His Glu Gln Tyr Leu Ile Asp Val Phe Val Phe Leu Leu Gly Leu Thr485 490 495Leu Gly Thr Met Trp Leu Cys Gly Lys Leu Leu Gly Val Val Ala Arg500 505 510Trp Leu Arg Gly Ala Arg Lys Val Lys Lys Thr515 520<210>67<211>252<212>PRT<213>人(Homo sapiens)<400>67Met Ser Cys Val Leu Gly Gly Val Ile Pro Leu Gly Leu Leu Phe Leul 5 10 15Val Cys Gly Ser Gln Gly Tyr Leu Leu Pro Asn Val Thr Leu Leu Glu20 25 30Glu Leu Leu Ser Lys Tyr Gln His Asn Glu Ser His Ser Arg Val Arg35 40 45Arg Ala Ile Pro Arg Glu Asp Lys Glu Glu Ile Leu Met Leu His Asn50 55 60Lys Leu Arg Gly Gln Val Gln Pro Gln Ala Ser Asn Met Glu Tyr Met65 70 75 80Thr Trp Asp Asp Glu Leu Glu Lys Ser Ala Ala Ala Trp Ala Ser Gln85 90 95Cys Ile Trp Glu His Gly Pro Thr Ser Leu Leu Val Ser Ile Gly Gln100 105 110Asn Leu Gly Ala His Trp Gly Arg Tyr Arg Ser Pro Gly Phe His Val115 120 125Gln Ser Trp Tyr Asp Glu Val Lys Asp Tyr Thr Tyr Pro Tyr Pro Ser130 135 140Glu Cys Asn Pro Trp Cys Pro Glu Arg Cys Ser Gly Pro Met Cys Thr145 150 155 160His Tyr Thr Gln Ile Val Trp Ala Thr Thr Asn Lys Ile Gly Cys Ala165 170 175Val Asn Thr Cys Arg Lys Met Thr Val Trp Gly Glu Val Trp Glu Asn180 185 190Ala Val Tyr Phe Val Cys Asn Tyr Ser Pro Lys Gly Asn Trp Ile Gly195 200 205Glu Ala Pro Tyr Lys Asn Gly Arg Pro Cys Ser Glu Cys Pro Pro Ser210 215 220Tyr Gly Gly Ser Cys Arg Asn Asn Leu Cys Tyr Arg Gly Arg Lys Phe225 230 235 240Thr Pro Asn Thr Phe Ala Met Asn Leu Pro Ser Val245 250<210>68<211>497<212>PRT<213>人(Homo sapiens)<400>68Met Ser Cys Val Leu Gly Gly Val Ile Pro Leu Gly Leu Leu Phe Leu1 5 10 15Val Cys Gly Ser Gln Gly Tyr Leu Leu Pro Asn Val Thr Leu Leu Glu20 25 30Glu Leu Leu Ser Lys Tyr Gln His Asn Glu Ser His Ser Arg Val Arg35 40 45Arg Ala Ile Pro Arg Glu Asp Lys Glu Glu Ile Leu Met Leu His Asn50 55 60Lys Leu Arg Gly Gln Val Gln Pro Gln Ala Ser Asn Met Glu Tyr Met65 70 75 80Thr Trp Asp Asp Glu Leu Glu Lys Ser Ala Ala Ala Trp Ala Ser Gln85 90 95Cys Ile Trp Glu His Gly Pro Thr Ser Leu Leu Val Ser Ile Gly Gln100 105 110Asn Leu Gly Ala His Trp Gly Arg Tyr Arg Ser Pro Gly Phe His Val115 120 125Gln Ser Trp Tyr Asp Glu Val Lys Asp Tyr Thr Tyr Pro Tyr Pro Ser130 135 140Glu Cys Asn Pro Trp Cys Pro Glu Arg Cys Ser Gly Pro Met Cys Thr145 150 155 160His Tyr Thr Gln Ile Val Trp Ala Thr Thr Asn Lys Ile Gly Cys Ala165 170 175Val Asn Thr Cys Arg Lys Met Thr Val Trp Gly Glu Val Trp Glu Asn180 185 190Ala Val Tyr Phe Val Cys Asn Tyr Ser Pro Lys Gly Asn Trp Ile Gly195 200 205Glu Ala Pro Tyr Lys Asn Gly Arg Pro Cys Ser Glu Cys Pro Pro Ser210 215 220Tyr Gly Gly Ser Cys Arg Asn Asn Leu Cys Tyr Arg Glu Glu Thr Tyr225 230 235 240Thr Pro Lys Pro Glu Thr Asp Glu Met Asn Glu Val Glu Thr Ala Pro245 250 255Ile Pro Glu Glu Asn His Val Trp Leu Gln Pro Arg Val Met Arg Pro260 265 270Thr Lys Pro Lys Lys Thr Ser Ala Val Asn Tyr Met Thr Gln Val Val275 280 285Arg Cys Asp Thr Lys Met Lys Asp Arg Cys Lys Gly Ser Thr Cys Asn290 295 300Arg Tyr Gln Cys Pro Ala Gly Cys Leu Asn His Lys Ala Lys Ile Phe305 310 315 320Gly Thr Leu Phe Tyr Glu Ser Ser Ser Ser Ile Cys Arg Ala Ala Ile325 330 335His Tyr Gly Ile Leu Asp Asp Lys Gly Gly Leu Val Asp Ile Thr Arg340 345 350Asn Gly Lys Val Pro Phe Phe Val Lys Ser Glu Arg His Gly Val Gln355 360 365Ser Leu Ser Lys Tyr Lys Pro Ser Ser Ser Phe Met Val Ser Lys Val370 375 380Lys Val Gln Asp Leu Asp Cys Tyr Thr Thr Val Ala Gln Leu Cys Pro385 390 395 400Phe Glu Lys Pro Ala Thr His Cys Pro Arg Ile His Cys Pro Ala His405 410 415Cys Lys Asp Glu Pro Ser Tyr Trp Ala Pro Val Phe Gly Thr Asn Ile420 425 430Tyr Ala Asp Thr Ser Ser Ile Cys Lys Thr Ala Val His Ala Gly Val435 440 445Ile Ser Asn Glu Ser Gly Gly Asp Val Asp Val Met Pro Val Asp Lys450 455 460Lys Lys Thr Tyr Val Gly Ser Leu Arg Asn Gly Val Gln Ser Glu Ser465 470 475 480Leu Gly Thr Pro Arg Asp Gly Lys Ala Phe Arg Ile Phe Ala Val Arg485 490 495Gln<210>69<211>438<212>PRT<213>人(Homo sapiens)<400>69Asx Met Leu His Asn Lys Leu Arg Gly Gln Val Gln Pro Gln Ala Ser1 5 10 15Asn Met Glu Tyr Met Thr Trp Asp Asp Glu Leu Glu Lys Ser Ala Ala20 25 30Ala Trp Ala Ser Gln Cys Ile Trp Glu His Gly Pro Thr Ser Leu Leu35 40 45Val Ser Ile Gly Gln Asn Leu Gly Ala His Trp Gly Arg Tyr Arg Ser50 55 60Pro Gly Phe His Val Gln Ser Trp Tyr Asp Glu Val Lys Asp Tyr Thr65 70 75 80Tyr Pro Tyr Pro Ser Glu Cys Asn Pro Trp Cys Pro Glu Arg Cys Ser85 90 95Gly Pro Met Cys Thr His Tyr Thr Gln Ile Val Trp Ala Thr Thr Asn100 105 110Lys Ile Gly Cys Ala Val Asn Thr Cys Arg Lys Met Thr Val Trp Gly115 120 125Glu Val Trp Glu Asn Ala Val Tyr Phe Val Cys Asn Tyr Ser Pro Lys130 135 140Gly Asn Trp Ile Gly Glu Ala Pro Tyr Lys Asn Gly Arg Pro Cys Ser145 150 155 160Glu Cys Pro Pro Ser Tyr Gly Gly Ser Cys Arg Asn Asn Leu Cys Tyr165 170 175Arg Glu Glu Thr Tyr Thr Pro Lys Pro Glu Thr Asp Glu Met Asn Glu180 185 190Val Glu Thr Ala Pro Ile Pro Glu Glu Asn His Val Trp Leu Gln Pro195 200 205Arg Val Met Arg Pro Thr Lys Pro Lys Lys Thr Ser Ala Val Asn Tyr210 215 220Met Thr Gln Val Val Arg Cys Asp Thr Lys Met Lys Asp Arg Cys Lys225 230 235 240Gly Ser Thr Cys Asn Arg Tyr Gln Cys Pro Ala Gly Cys Leu Asn His245 250 255Lys Ala Lys Ile Phe Gly Thr Leu Phe Tyr Glu Ser Ser Ser Ser Ile260 265 270Cys Arg Ala Ala Ile His Tyr Gly Ile Leu Asp Asp Lys Gly Gly Leu275 280 285Val Asp Ile Thr Arg Asn Gly Lys Val Pro Phe Phe Val Lys Ser Glu290 295 300Arg His Gly Val Gln Ser Leu Ser Lys Tyr Lys Pro Ser Ser Ser Phe305 310 315 320Met Val Ser Lys Val Lys Val Gln Asp Leu Asp Cys Tyr Thr Thr Val325 330 335Ala Gln Leu Cys Pro Phe Glu Lys Pro Ala Thr His Cys Pro Arg Ile340 345 350His Cys Pro Ala His Cys Lys Asp Glu Pro Ser Tyr Trp Ala Pro Val355 360 365Phe Gly Thr Asn Ile Tyr Ala Asp Thr Ser Ser Ile Cys Lys Thr Ala370 375 380Val His Ala Gly Val Ile Ser Asn Glu Ser Gly Gly Asp Val Asp Val385 390 395 400Met Pro Val Asp Lys Lys Lys Thr Tyr Val Gly Ser Leu Arg Asn Gly405 410 415Val Gln Ser Glu Ser Leu Gly Thr Pro Arg Asp Gly Lys Ala Phe Arg420 425 430Ile Phe Ala Val Arg Gln435<210>70<211>308<212>PRT<213>人(Homo sapiens)<400>70Met Val Gly Gly Val Leu Ala Ser Leu Gly Phe Val Phe Ser Ala Phe1 5 10 15Ala Ser Asp Leu Leu His Leu Tyr Leu Gly Leu Gly Leu Leu Ala Gly20 25 30Phe Gly Trp Ala Leu Val Phe Ala Pro Ala Leu Gly Thr Leu Ser Arg35 40 45Tyr Phe Ser Arg Arg Arg Val Leu Ala Val Gly Leu Ala Leu Thr Gly50 55 60Asn Gly Ala Ser Ser Leu Leu Leu Ala Pro Ala Leu Gln Leu Leu Leu65 70 75 80Asp Thr Phe Gly Trp Arg Gly Ala Leu Leu Leu Leu Gly Ala Ile Thr85 90 95Leu His Leu Thr Pro Cys Gly Ala Leu Leu Leu Pro Leu Val Leu Pro100 105 110Gly Asp Pro Pro Ala Pro Pro Arg Ser Pro Leu Ala Ala Leu Gly Leu115 120 125Ser Leu Phe Thr Arg Arg Ala Phe Ser Ile Phe Ala Leu Gly Thr Ala130 135 140Leu Val Gly Gly Gly Tyr Phe Val Pro Tyr Val His Leu Ala Pro His145 150 155 160Ala Leu Asp Arg Gly Leu Gly Gly Tyr Gly Ala Ala Leu Val Val Ala165 170 175Val Ala Ala Met Gly Asp Ala Gly Ala Arg Leu Val Cys Gly Trp Leu180 185 190Ala Asp Gln Gly Trp Val Pro Leu Pro Arg Leu Leu Ala Val Phe Gly195 200 205Ala Leu Thr Gly Leu Gly Leu Trp Val Val Gly Leu Val Pro Val Val210 215 220Gly Gly Glu Glu Ser Trp Gly Gly Pro Leu Leu Ala Ala Ala Val Ala225 230 235 240Tyr Gly Leu Ser Ala Gly Ser Tyr Ala Pro Leu Val Phe Gly Val Leu245 250 255Pro Gly Leu Val Gly Val Gly Gly Val Val Gln Ala Thr Gly Leu Val260 265 270Met Met Leu Met Ser Leu Gly Gly Leu Leu Gly Pro Pro Leu Ser Gly275 280 285Lys Asp Leu Ser Ser Gln Ile Cys Leu Gln Leu Ser Ser Ala Pro Gly290 295 300Val Arg Gly Phe305<210>71<211>447<212>PRT<213>人(Homo sapiens)<400>71Met Thr Pro Gln Pro Ala Gly Pro Pro Asp Gly Gly Trp Gly Trp Val1 5 10 15Val Ala Ala Ala Ala Phe Ala Ile Asn Gly Leu Ser Tyr Gly Leu Leu20 25 30Arg Ser Leu Gly Leu Ala Phe Pro Asp Leu Ala Glu His Phe Asp Arg35 40 45Ser Ala Gln Asp Thr Ala Trp Ile Ser Ala Leu Ala Leu Ala Val Gln50 55 60Gln Ala Ala Ser Pro Val Gly Ser Ala Leu Ser Thr Arg Trp Gly Ala65 70 75 80Arg Pro Val Val Met Val Gly Gly Val Leu Ala Ser Leu Gly Phe Val85 90 95Phe Ser Ala Phe Ala Ser Asp Leu Leu His Leu Tyr Leu Gly Leu Gly100 105 110Leu Leu Ala Gly Phe Gly Trp Ala Leu Val Phe Ala Pro Ala Leu Gly115 120 125Thr Leu Ser Arg Tyr Phe Ser Arg Arg Arg Val Leu Ala Val Gly Leu130 135 140Ala Leu Thr Gly Asn Gly Ala Ser Ser Leu Leu Leu Ala Pro Ala Leu145 150 155 160Gln Leu Leu Leu Asp Thr Phe Gly Trp Arg Gly Ala Leu Leu Leu Leu165 170 175Gly Ala Ile Thr Leu His Leu Thr Pro Cys Gly Ala Leu Leu Leu Pro180 185 190Leu Val Leu Pro Gly Asp Pro Pro Ala Pro Pro Arg Ser Pro Leu Ala195 200 205Ala Leu Gly Leu Ser Leu Phe Thr Arg Arg Ala Phe Ser Ile Phe Ala210 215 220Leu Gly Thr Ala Leu Val Gly Gly Gly Tyr Phe Val Pro Tyr Val His225 230 235 240Leu Ala Pro His Ala Leu Asp Arg Gly Leu Gly Gly Tyr Gly Ala Ala245 250 255Leu Val Val Ala Val Ala Ala Met Gly Asp Ala Gly Ala Arg Leu Val260 265 270Cys Gly Trp Leu Ala Asp Gln Gly Trp Val Pro Leu Pro Arg Leu Leu275 280 285Ala Val Phe Gly Ala Leu Thr Gly Leu Gly Leu Trp Val Val Gly Leu290 295 300Val Pro Val Val Gly Gly Glu Glu Ser Trp Gly Gly Pro Leu Leu Ala305 310 315 320Ala Ala Val Ala Tyr Gly Leu Ser Ala Gly Ser Tyr Ala Pro Leu Val325 330 335Phe Gly Val Leu Pro Gly Leu Val Gly Val Gly Gly Val Val Gln Ala340 345 350Thr Gly Leu Val Met Met Leu Met Ser Leu Gly Gly Leu Leu Gly Pro355 360 365Pro Leu Ser Gly Phe Leu Arg Asp Glu Thr Gly Asp Phe Thr Ala Ser370 375 380Phe Leu Leu Ser Gly Ser Leu Ile Leu Ser Gly Ser Phe Ile Tyr Ile385 390 395 400Gly Leu Pro Arg Ala Leu Pro Ser Cys Gly Pro Ala Ser Pro Pro Ala405 410 415Thr Pro Pro Pro Glu Thr Gly Glu Leu Leu Pro Ala Pro Gln Ala Val420 425 430Leu Leu Ser Pro Gly Gly Pro Gly Ser Thr Leu Asp Thr Thr Cys435 440 445<210>72<211>458<212>PRT<213>人(Homo sapiens)<400>72Asx Met Ala Arg Arg Thr Glu Pro Pro Asp Gly Gly Trp Gly Trp Val1 5 10 15Val Val Leu Ser Ala Phe Phe Gln Ser Ala Leu Val Phe Gly Val Leu20 25 30Arg Ser Phe Gly Val Phe Phe Val Glu Phe Val Ala Ala Phe Glu Glu35 40 45Gln Ala Ala Arg Val Ser Trp Ile Ala Ser Ile Gly Ile Ala Val Gln50 55 60Gln Phe Gly Ser Pro Val Gly Ser Ala Leu Ser Thr Lys Phe Gly Pro65 70 75 80Arg Pro Val Val Met Thr Gly Gly Ile Leu Ala Ala Leu Gly Met Leu85 90 95Leu Ala Ser Phe Ala Thr Ser Leu Thr His Leu Tyr Leu Ser Ile Gly100 105 110Leu Leu Ser Gly Ser Gly Trp Ala Leu Thr Phe Ala Pro Thr Leu Ala115 120 125Cys Leu Ser Cys Tyr Phe Ser Arg Arg Arg Ser Leu Ala Thr Gly Leu130 135 140Ala Leu Thr Gly Val Gly Leu Ser Ser Phe Thr Phe Ala Pro Phe Phe145 150 155 160Gln Trp Leu Leu Ser His Tyr Ala Trp Arg Gly Ser Leu Leu Leu Val165 170 175Ser Ala Leu Ser Leu His Leu Val Ala Cys Gly Ala Leu Leu Arg Pro180 185 190Pro Ser Leu Ala Glu Asp Pro Ala Val Gly Gly Pro Arg Ala Gln Leu195 200 205Thr Ser Leu Leu His His Gly Pro Phe Leu Arg Tyr Thr Val Ala Leu210 215 220Thr Leu Ile Asn Thr Gly Tyr Phe Ile Pro Tyr Leu His Leu Val Ala225 230 235 240His Leu Gln Asp Leu Asp Trp Asp Pro Leu Pro Ala Ala Phe Leu Leu245 250 255Ser Val Val Ala Ile Ser Asp Leu Val Gly Arg Val Val Ser Gly Trp260 265 270Leu Gly Asp Ala Val Pro Gly Pro Val Thr Arg Leu Leu Met Leu Trp275 280 285Thr Thr Leu Thr Gly Val Ser Leu Ala Leu Phe Pro Val Ala Gln Ala290 295 300Pro Thr Ala Leu Val Ala Leu Ala Val Ala Tyr Gly Phe Thr Ser Gly305 310 315 320Ala Leu Ala Pro Leu Ala Phe Ser Val Leu Pro Glu Leu Ile Gly Thr325 330 335Arg Arg Ile Tyr Cys Gly Leu Gly Leu Leu Gln Met Ile Glu Ser Ile340 345 350Gly Gly Leu Leu Gly Pro Pro Leu Ser Gly Tyr Leu Arg Asp Val Ser355 360 365Gly Asn Tyr Thr Ala Ser Phe Val Val Ala Gly Ala Phe Leu Leu Ser370 375 380Gly Ser Gly Ile Leu Leu Thr Leu Pro His Phe Phe Cys Phe Ser Thr385 390 395 400Thr Thr Ser Gly Pro Gln Asp Leu Val Thr Glu Ala Leu Asp Thr Lys405 410 415Val Pro Leu Pro Lys Glu Gly Leu Glu Gly Gly Leu Asn Ser Thr Glu420 425 430Ser Gly Pro Glu Ser Gln Ser Leu Thr Ala Pro Gly Leu Leu Leu Pro435 440 445Arg Leu Gly Leu His Arg Thr Thr Val Pro450 455<210>73<211>169<212>PRT<213>人(Homo sapiens)<400>73Met Thr Met Lys Thr Ser Gly Ala Thr Cys Asp Ala Asn Ser Val Met1 5 10 15Asn Cys Gly Ile Arg Gly Ser Glu Met Phe Ala Glu Met Asp Leu Arg20 25 30Ala Ile Lys Pro Tyr Gln Thr Leu Ile Lys Lys Val Gly Gln Arg His35 40 45Cys Val Asp Pro Ala Val Ile Ala Ala Ile Ile Ser Arg Glu Ser His50 55 60Gly Gly Ser Val Leu Gln Asp Gly Trp Asp His Arg Gly Leu Lys Phe65 70 75 80Gly Leu Met Gln Leu Asp Lys Gln Thr Tyr His Pro Val Gly Ala Trp85 90 95Asp Ser Lys Glu His Leu Ser Gln Ala Thr Gly Ile Leu Thr Glu Arg100 105 110Ile Lys Ala Ile Gln Lys Lys Phe Pro Thr Trp Ser Val Ala Gln His115 120 125Leu Lys Gly Gly Leu Ser Ala Phe Lys Ser Gly Ile Glu Ala Ile Ala130 135 140Thr Pro Ser Asp Ile Asp Asn Asp Phe Val Asn Asp Ile Ile Ala Arg145 150 155 160Ala Lys Phe Tyr Lys Arg Gln Ser Phe165<210>74<211>186<212>PRT<213>人(Homo sapiens)<400>74Met Lys Pro His Leu His Pro Arg Leu Tyr His Gly Cys Tyr Gly Asp1 5 10 15Ile Met Thr Met Lys Thr Ser Gly Ala Thr Cys Asp Ala Asn Ser Val20 25 30Met Asn Cys Gly Ile Arg Gly Ser Glu Met Phe Ala Glu Met Asp Leu35 40 45Arg Ala Ile Lys Pro Tyr Gln Thr Leu Ile Lys Lys Val Gly Gln Arg50 55 60His Cys Val Asp Pro Ala Val Ile Ala Ala Ile Ile Ser Arg Glu Ser65 70 75 80His Gly Gly Ser Val Leu Gln Asp Gly Trp Asp His Arg Gly Leu Lys85 90 95Phe Gly Leu Met Gln Leu Asp Lys Gln Thr Tyr His Pro Val Gly Ala100 105 110Trp Asp Ser Lys Glu His Leu Ser Gln Ala Thr Gly Ile Leu Thr Glu115 120 125Arg Ile Lys Ala Ile Gln Lys Lys Phe Pro Thr Trp Ser Val Ala Gln130 135 140His Leu Lys Gly Gly Leu Ser Ala Phe Lys Ser Gly Ile Glu Ala Ile145 150 155 160Ala Thr Pro Ser Asp Ile Asp Asn Asp Phe Val Asn Asp Ile Ile Ala165 170 175Arg Ala Lys Phe Tyr Lys Arg Gln Ser Phe180 185<210>75<211>675<212>PRT<213>人(Homo sapiens)<400>75Met Glu Ser Gly Thr Ser Ser Pro Gln Pro Pro Gln Leu Asp Pro Leu1 5 10 15Asp Ala Phe Pro Gln Lys Gly Leu Glu Pro Gly Asp Ile Ala Val Leu20 25 30Val Leu Tyr Phe Leu Phe Val Leu Ala Val Gly Leu Trp Ser Thr Val35 40 45Lys Thr Lys Arg Asp Thr Val Lys Gly Tyr Phe Leu Ala Gly Gly Asp50 55 60Met Val Trp Trp Pro Val Gly Ala Ser Leu Phe Ala Ser Asn Val Gly65 70 75 80Ser Gly His Phe Ile Gly Leu Ala Gly Ser Gly Ala Ala Thr Gly Ile85 90 95Ser Val Ser Ala Tyr Glu Leu Asn Gly Leu Phe Ser Val Leu Met Leu100 105 110Ala Trp Ile Phe Leu Pro Ile Tyr Ile Ala Gly Gln Val Thr Thr Met115 120 125Pro Glu Tyr Leu Arg Lys Arg Phe Gly Gly Ile Arg Ile Pro Ile Ile130 135 140Leu Ala Val Leu Tyr Leu Phe Ile Tyr Ile Phe Thr Lys Ile Ser Val145 150 155 160Asp Met Tyr Ala Gly Ala Ile Phe Ile Gln Gln Ser Leu His Leu Asp165 170 175Leu Tyr Leu Ala Ile Val Gly Leu Leu Ala Ile Thr Ala Val Tyr Thr180 185 190Val Ala Gly Gly Leu Ala Ala Val Ile Tyr Thr Asp Ala Leu Gln Thr195 200 205Leu Ile Met Leu Ile Gly Ala Leu Thr Leu Met Gly Tyr Ser Phe Ala210 215 220Ala Val Gly Gly Met Glu Gly Leu Lys Glu Lys Tyr Phe Leu Ala Leu225 230 235 240Ala Ser Asn Arg Ser Glu Asn Ser Ser Cys Gly Leu Pro Arg Glu Asp245 250 255Ala Phe His Ile Phe Arg Asp Pro Leu Thr Ser Asp Leu Pro Trp Pro260 265 270Gly Val Leu Phe Gly Met Ser Ile Pro Ser Leu Trp Tyr Trp Cys Thr275 280 285Asp Gln Val Ile Val Gln Arg Thr Leu Ala Ala Lys Asn Leu Ser His290 295 300Ala Lys Gly Gly Ala Leu Met Ala Ala Tyr Leu Lys Val Leu Pro Leu305 3l0 315 320Phe Ile Met Val Phe Pro Gly Met Val Ser Arg Ile Leu Phe Pro Asp325 330 335Gln Val Ala Cys Ala Asp Pro Glu Ile Cys Gln Lys Ile Cys Ser Asn340 345 350Pro Ser Gly Cys Ser Asp Ile Ala Tyr Pro Lys Leu Val Leu Glu Leu355 360 365Leu Pro Thr Gly Leu Arg Gly Leu Met Met Ala Val Met Val Ala Ala370 375 380Leu Met Ser Ser Leu Thr Ser Ile Phe Asn Ser Ala Ser Thr Ile Phe385 390 395 400Thr Met Asp Leu Trp Asn His Leu Arg Pro Arg Ala Ser Glu Lys Glu405 410 415Leu Met Ile Val Gly Arg Val Phe Val Leu Leu Leu Val Leu Val Ser420 425 430Ile Leu Trp Ile Pro Val Val Gln Ala Ser Gln Gly Gly Gln Leu Phe435 440 445Ile Tyr Ile Gln Ser Ile Ser Ser Tyr Leu Gln Pro Pro Val Ala Val450 455 460Val Phe Ile Met Gly Cys Phe Trp Lys Arg Thr Asn Glu Lys Gly Ala465 470 475 480Phe Trp Gly Leu Ile Ser Gly Leu Leu Leu Gly Leu Val Arg Leu Val485 490 495Leu Asp Phe Ile Tyr Val Gln Pro Arg Cys Asp Gln Pro Asp Glu Arg500 505 510Pro Val Leu Val Lys Ser Ile His Tyr Leu Tyr Phe Ser Met Ile Leu515 520 525Ser Thr Val Thr Leu Ile Thr Val Ser Thr Val Ser Trp Phe Thr Glu530 535 540Pro Pro Ser Lys Glu Met Val Ser His Leu Thr Trp Phe Thr Arg His545 550 555 560Asp Pro Val Val Gln Lys Glu Gln Ala Pro Pro Ala Ala Pro Leu Ser565 570 575Leu Thr Leu Ser Gln Asn Gly Met Pro Glu Ala Ser Ser Ser Ser Ser580 585 590Val Gln Phe Glu Met Val Gln Glu Asn Thr Ser Lys Thr His Ser Cys595 600 605Asp Met Thr Pro Lys Gln Ser Lys Val Val Lys Ala Ile Leu Trp Leu610 615 620Cys Gly Ile Gln Glu Lys Gly Lys Glu Glu Leu Pro Ala Arg Ala Glu625 630 635 640Ala Ile Ile Val Ser Leu Glu Glu Asn Pro Leu Val Lys Thr Leu Leu645 650 655Asp Val Asn Leu Ile Phe Cys Val Ser Cys Ala Ile Phe Ile Trp Gly660 665 670Tyr Phe Ala675<210>76<211>485<212>PRT<213>人(Homo sapiens)<400>76Met Glu Pro Cys Trp Gly Glu Gly Leu Phe His Leu Ala Pro Pro Arg1 5 10 15His His Pro Gln Lys Ala Asp Trp His Phe Cys Pro Gln His Ile Gln20 25 30Glu Phe Thr Asn Glu Thr Trp Gln Ala Arg Thr Gly Glu Pro Leu Pro35 40 45Asp His Leu Val Leu Leu Met Trp Ser Leu Ile Val Ser Leu Tyr Pro50 55 60Leu Gly Gly Leu Phe Gly Ala Leu Leu Ala Gly Pro Leu Ala Ile Thr65 70 75 80Leu Gly Arg Lys Lys Ser Leu Leu Val Asn Asn Ile Phe Val Val Ser85 90 95Ala Ala Ile Leu Phe Gly Phe Ser Arg Lys Ala Gly Ser Phe Glu Met100 105 110Ile Met Leu Gly Arg Leu Leu Val Gly Val Asn Ala Gly Val Ser Met115 120 125Asn Ile Gln Pro Met Tyr Leu Gly Glu Ser Ala Pro Lys Glu Leu Arg130 135 140Gly Ala Val Ala Met Ser Ser Ala Ile Phe Thr Ala Leu Gly Ile Val145 150 155 160Met Gly Gln Val Val Gly Leu Arg Glu Leu Leu Gly Gly Pro Gln Ala165 170 175Trp Pro Leu Leu Leu Ala Ser Cys Leu Val Pro Gly Ala Leu Gln Leu180 185 190Ala Ser Leu Pro Leu Leu Pro Glu Ser Pro Arg Tyr Leu Leu Ile Asp195 200 205Cys Gly Asp Thr Glu Ala Cys Leu Ala Ala Leu Arg Arg Leu Arg Gly210 215 220Ser Gly Asp Leu Ala Gly Glu Leu Glu Glu Leu Glu Glu Glu Arg Ala225 230 235 240Ala Cys Gln Gly Cys Arg Ala Arg Arg Pro Trp Glu Leu Phe Gln His245 250 255Arg Ala Leu Arg Arg Gln Val Thr Ser Leu Val Val Leu Gly Ser Ala260 265 270Met Glu Leu Cys Gly Asn Asp Ser Val Tyr Ala Tyr Ala Ser Ser Val275 280 285Phe Arg Lys Ala Gly Val Pro Glu Ala Lys Ile Gln Tyr Ala Ile Ile290 295 300Gly Thr Gly Ser Cys Glu Leu Leu Thr Ala Val Val Ser Cys Val Val305 310 315 320Ile Glu Arg Val Gly Arg Arg Val Leu Leu Ile Gly Gly Tyr Ser Leu325 330 335Met Thr Cys Trp Gly Ser Ile Phe Thr Val Ala Leu Cys Leu Gln Ser340 345 350Ser Phe Pro Trp Thr Leu Tyr Leu Ala Met Ala Cys Ile Phe Ala Phe355 360 365Ile Leu Ser Phe Gly Ile Gly Pro Ala Gly Val Thr Gly Ile Leu Ala370 375 380Thr Glu Leu Phe Asp Gln Met Ala Arg Pro Ala Ala Cys Met Val Cys385 390 395 400Gly Ala Leu Met Trp Ile Met Leu Ile Leu Val Gly Leu Gly Phe Pro405 410 415Phe Ile Met Glu Ala Leu Ser His Phe Leu Tyr Val Pro Phe Leu Gly420 425 430Val Cys Val Cys Gly Ala Ile Tyr Thr Gly Leu Phe Leu Pro Glu Thr435 440 445Lys Gly Lys Thr Phe Gln Glu Ile Ser Lys Glu Leu His Arg Leu Asn450 455 460Phe Pro Arg Arg Ala Gln Gly Pro Thr Trp Arg Ser Leu Glu Val Ile465 470 475 480Gln Ser Thr Glu Leu485<210>77<211>496<212>PRT<213>人(Homo sapiens)<400>77Met Arg Ala Leu Arg Arg Leu Ile Gln Gly Arg Ile Leu Leu Leu Thr1 5 10 15Ile Cys Ala Ala Gly Ile Gly Gly Thr Phe Gln Phe Gly Tyr Asn Leu20 25 30Ser Ile Ile Asn Ala Pro Thr Leu His Ile Gln Glu Phe Thr Asn Glu35 40 45Thr Trp Gln Ala Arg Thr Gly Glu Pro Leu Pro Asp His Leu Val Leu50 55 60Leu Met Trp Ser Leu Ile Val Ser Leu Tyr Pro Leu Gly Gly Leu Phe65 70 75 80Gly Ala Leu Leu Ala Gly Pro Leu Ala Ile Thr Leu Gly Arg Lys Lys85 90 95Ser Leu Leu Val Asn Asn Ile Phe Val Val Ser Ala Ala Ile Leu Phe100 105 110Gly Phe Ser Arg Lys Ala Gly Ser Phe Glu Met Ile Met Leu Gly Arg115 120 125Leu Leu Val Gly Val Asn Ala Gly Val Ser Met Asn Ile Gln Pro Met130 135 140Tyr Leu Gly Glu Ser Ala Pro Lys Glu Leu Arg Gly Ala Val Ala Met145 150 155 160Ser Ser Ala Ile Phe Thr Ala Leu Gly Ile Val Met Gly Gln Val Val165 170 175Gly Leu Arg Glu Leu Leu Gly Gly Pro Gln Ala Trp Pro Leu Leu Leu180 185 190Ala Ser Cys Leu Val Pro Gly Ala Leu Gln Leu Ala Ser Leu Pro Leu195 200 205Leu Pro Glu Ser Pro Arg Tyr Leu Leu Ile Asp Cys Gly Asp Thr Glu210 215 220Ala Cys Leu Ala Ala Leu Arg Arg Leu Arg Gly Ser Gly Asp Leu Ala225 230 235 240Gly Glu Leu Glu Glu Leu Glu Glu Glu Arg Ala Ala Cys Gln Gly Cys245 250 255Arg Ala Arg Arg Pro Trp Glu Leu Phe Gln Hi s Arg Ala Leu Arg Arg260 265 270Gln Val Thr Ser Leu Val Val Leu Gly Ser Ala Met Glu Leu Cys Gly275 280 285Asn Asp Ser Val Tyr Ala Tyr Ala Ser Ser Val Phe Arg Lys Ala Gly290 295 300Val Pro Glu Ala Lys Ile Gln Tyr Ala Ile Ile Gly Thr Gly Ser Cys305 310 315 320Glu Leu Leu Thr Ala Val Val Ser Cys Val Val Ile Glu Arg Val Gly325 330 335Arg Arg Val Leu Leu Ile Gly Gly Tyr Ser Leu Met Thr Cys Trp Gly340 345 350Ser Ile Phe Thr Val Ala Leu Cys Leu Gln Ser Ser Phe Pro Trp Thr355 360 365Leu Tyr Leu Ala Met Ala Cys Ile Phe Ala Phe Ile Leu Ser Phe Gly370 375 380Ile Gly Pro Ala Gly Val Thr Gly Ile Leu Ala Thr Glu Leu Phe Asp385 390 395 400Gln Met Ala Arg Pro Ala Ala Cys Met Val Cys Gly Ala Leu Met Trp405 410 415Ile Met Leu Ile Leu Val Gly Leu Gly Phe Pro Phe Ile Met Glu Ala420 425 430Leu Ser His Phe Leu Tyr Val Pro Phe Leu Gly Val Cys Val Cys Gly435 440 445Ala Ile Tyr Thr Gly Leu Phe Leu Pro Glu Thr Lys Gly Lys Thr Phe450 455 460Gln Glu Ile Ser Lys Glu Leu His Arg Leu Asn Phe Pro Arg Arg Ala465 470 475 480Gln Gly Pro Thr Trp Arg Ser Leu Glu Val Ile Gln Ser Thr Glu Leu485 490 495<210>78<211>500<212>PRT<213>人(Homo sapiens)<400>78Asx Met Leu His Ala Leu Leu Arg Ser Arg Met Ile Gln Gly Arg Ile1 5 10 15Leu Leu Leu Thr Ile Cys Ala Ala Gly Ile Gly Gly Thr Phe Gln Phe20 25 30Gly Tyr Asn Leu Ser Ile Ile Asn Ala Pro Thr Leu His Ile Gln Glu35 40 45Phe Thr Asn Glu Thr Trp Gln Ala Arg Thr Gly Glu Pro Leu Pro Asp50 55 60His Leu Val Leu Leu Met Trp Ser Leu Ile Val Ser Leu Tyr Pro Leu65 70 75 80Gly Gly Leu Phe Gly Ala Leu Leu Ala Gly Pro Leu Ala Ile Thr Leu85 90 95Gly Arg Lys Lys Ser Leu Leu Val Asn Asn Ile Phe Val Val Ser Ala100 105 110Ala Ile Leu Phe Gly Phe Ser Arg Lys Ala Gly Ser Phe Glu Met Ile115 120 125Met Leu Gly Arg Leu Leu Val Gly Val Asn Ala Gly Val Ser Met Asn130 135 140Ile Gln Pro Met Tyr Leu Gly Glu Ser Ala Pro Lys Glu Leu Arg Gly145 150 155 160Ala Val Ala Met Ser Ser Ala Ile Phe Thr Ala Leu Gly Ile Val Met165 170 175Gly Gln Val Val Gly Leu Arg Glu Leu Leu Gly Gly Pro Gln Ala Trp180 185 190Pro Leu Leu Leu Ala Ser Cys Leu Val Pro Gly Ala Leu Gln Leu Ala195 200 205Ser Leu Pro Leu Leu Pro Glu Ser Pro Arg Tyr Leu Leu Ile Asp Cys210 215 220Gly Asp Thr Glu Ala Cys Leu Ala Ala Leu Arg Arg Leu Arg Gly Ser225 230 235 240Gly Asp Leu Ala Gly Glu Leu Glu Glu Leu Glu Glu Glu Arg Ala Ala245 250 255Cys Gln Gly Cys Arg Ala Arg Arg Pro Trp Glu Leu Phe Gln His Arg260 265 270Ala Leu Arg Arg Gln Val Thr Ser Leu Val Val Leu Gly Ser Ala Met275 280 285Glu Leu Cys Gly Asn Asp Ser Val Tyr Ala Tyr Ala Ser Ser Val Phe290 295 300Arg Lys Ala Gly Val Pro Glu Ala Lys Ile Gln Tyr Ala Ile Ile Gly305 310 315 320Thr Gly Ser Cys Glu Leu Leu Thr Ala Val Val Ser Cys Val Val Ile325 330 335Glu Arg Val Gly Arg Arg Val Leu Leu Ile Gly Gly Tyr Ser Leu Met340 345 350Thr Cys Trp Gly Ser Ile Phe Thr Val Ala Leu Cys Leu Gln Ser Ser355 360 365Phe Pro Trp Thr Leu Tyr Leu Ala Met Ala Cys Ile Phe Ala Phe Ile370 375 380Leu Ser Phe Gly Ile Gly Pro Ala Gly Val Thr Gly Ile Leu Ala Thr385 390 395 400Glu Leu Phe Asp Gln Met Ala Arg Pro Ala Ala Cys Met Val Cys Gly405 410 415Ala Leu Met Trp Ile Met Leu Ile Leu Val Gly Leu Gly Phe Pro Phe420 425 430Ile Met Glu Ala Leu Ser His Phe Leu Tyr Val Pro Phe Leu Gly Val435 440 445Cys Val Cys Gly Ala Ile Tyr Thr Gly Leu Phe Leu Pro Glu Thr Lys450 455 460Gly Lys Thr Phe Gln Glu Ile Ser Lys Glu Leu His Arg Leu Asn Phe465 470 475 480Pro Arg Arg Ala Gln Gly Pro Thr Trp Arg Ser Leu Glu Val Ile Gln485 490 495Ser Thr Glu Leu500<210>79<211>1358<212>PRT<213>人(Homo sapiens)<400>79Met Val Val Val Lys Pro Met Asn Thr Met Ala Pro Val Val Thr Arg1 5 10 15Asn Thr Gly Leu Ile Leu Tyr Glu Gly Gln Ser Arg Pro Leu Thr Gly20 25 30Pro Ala Gly Ser Gly Pro Gln Asn Leu Val Ile Ser Asp Glu Asp Asp35 40 45Leu Glu Ala Val Arg Leu Glu Val Val Ala Gly Leu Arg His Gly His50 55 60Leu Val Ile Leu Gly Ala Ser Ser Gly Ser Ser Ala Pro Lys Ser Phe65 70 75 80Thr Val Ala Glu Leu Ala Ala Gly Gln Val Val Tyr Gln His Asp Asp85 90 95Arg Asp Gly Ser Leu Ser Asp Asn Leu Val Leu Arg Met Val Asp Gly100 105 1l0Gly Gly Arg His Gln Val Gln Phe Leu Phe Pro Ile Thr Leu Val Pro115 120 125Val Asp Asp Gln Pro Pro Val Leu Asn Ala Asn Thr Gly Leu Thr Leu130 135 140Ala Glu Gly Glu Thr Val Pro Ile Leu Pro Leu Ser Leu Ser Ala Thr145 150 155 160Asp Met Asp Ser Asp Asp Ser Leu Leu Leu Phe Val Leu Glu Ser Pro165 170 175Phe Leu Thr Thr Gly His Leu Leu Leu Arg Gln Thr His Pro Pro His180 185 190Glu Lys Gln Glu Leu Leu Arg Gly Leu Trp Arg Lys Glu Gly Ala Phe195 200 205Tyr Glu Arg Thr Val Thr Glu Trp Gln Gln Gln Asp Ile Thr Glu Gly210 215 220Arg Leu Phe Tyr Arg His Ser Gly Pro His Ser Pro Gly Pro Val Thr225 230 235 240Asp Gln Phe Thr Phe Arg Val Gln Asp Asn His Asp Pro Pro Asn Gln245 250 255Ser Gly Leu Gln Arg Phe Val Ile Arg Ile His Pro Val Asp Arg Leu260 265 270Pro Pro Glu Leu Gly Ser Gly Cys Pro Leu Arg Met Val Val Gln Glu275 280 285Ser Gln Leu Thr Pro Leu Arg Lys Lys Trp Leu Arg Tyr Thr Asp Leu290 295 300Asp Thr Asp Asp Arg Glu Leu Arg Tyr Thr Val Thr Gln Ser Pro Thr305 310 315 320Asp Thr Asp Glu Asn His Leu Pro Ala Pro Leu Gly Thr Leu Val Leu325 330 335Thr Asp Asn Pro Ser Val Val Val Thr His Phe Thr Gln Ala Gln Ile340 345 350Asn His His Lys Ile Ala Tyr Arg Pro Pro Gly Gln Glu Leu Gly Val355 360 365Ala Thr Arg Val Ala Gln Phe Gln Phe Gln Val Glu Asp Arg Ala Gly370 375 380Asn Val Ala Pro Gly Thr Phe Thr Leu Tyr Leu His Pro Val Asp Asn385 390 395 400Gln Pro Pro Glu Ile Leu Asn Thr Gly Phe Thr Ile Gln Glu Lys Gly405 410 415His His Ile Leu Ser Glu Thr Glu Leu His Val Asn Asp Val Asp Thr420 425 430Asp Val Ala His Ile Ser Phe Thr Leu Thr Gln Ala Pro Lys His Gly435 440 445His Met Arg Val Ser Gly Gln Ile Leu His Val Gly Gly Leu Phe His450 455 460Leu Glu Asp Ile Lys Gln Gly Arg Val Ser Tyr Ala His Asn Gly Asp465 470 475 480Lys Ser Leu Thr Asp Ser Cys Ser Leu Glu Val Ser Asp Arg His His485 490 495Val Val Pro Ile Thr Leu Arg Val Asn Val Arg Pro Val Asp Asp Glu500 505 510Val Pro Ile Leu Ser His Pro Thr Gly Thr Leu Glu Ser Tyr Leu Asp515 520 525Val Leu Glu Asn Gly Ala Thr Glu Ile Thr Ala Asn Val Ile Lys Gly530 535 540Thr Asn Glu Glu Thr Asp Asp Leu Met Leu Thr Phe Leu Leu Glu Asp545 550 555 560Pro Pro Leu Tyr Gly Glu Ile Leu Val Asn Gly Ile Pro Ala Glu Gln565 570 575Phe Thr Gln Arg Asp Ile Leu Glu Gly Ser Val Val Tyr Thr His Thr580 585 590Ser Gly Glu Ile Gly Leu Leu Pro Lys Ala Asp Ser Phe Asn Leu Ser595 600 605Leu Ser Asp Met Ser Gln Glu Trp Arg Ile Gly Gly Asn Thr Ile Gln610 615 620Gly Val Thr Ile Trp Val Thr Ile Leu Pro Val Asp Ser Gln Ala Pro625 630 635 640Glu Ile Phe Val Gly Glu Gln Leu Ile Val Met Glu Gly Asp Lys Ser645 650 655Val Ile Thr Ser Val His Ile Ser Ala Glu Asp Val Asp Ser Leu Asn660 665 670Asp Asp Ile Leu Cys Thr Ile Val Ile Gln Pro Thr Ser Gly Tyr Val675 680 685Glu Asn Ile Ser Pro Ala Pro Gly Ser Glu Lys Ser Arg Ala Gly Ile690 695 700Ala Ile Ser Ala Phe Asn Leu Lys Asp Leu Arg Gln Gly His Ile Asn705 710 715 720Tyr Val Gln Ser Val His Lys Gly Val Glu Pro Val Glu Asp Arg Phe725 730 735Val Phe Arg Cys Ser Asp Gly Ile Asn Phe Ser Glu Arg Gln Phe Phe740 745 750Pro Ile Val Ile Ile Pro Thr Asn Asp Glu Gln Pro Glu Met Phe Met755 760 765Arg Glu Phe Met Val Met Glu Gly Met Ser Leu Val Ile Asp Thr Pro770 775 780Ile Leu Asn Ala Ala Asp Ala Asp Val Pro Leu Asp Asp Leu Thr Phe785 790 795 800Thr Ile Thr Gln Phe Pro Thr His Gly His Ile Met Asn Gln Leu Ile805 810 815Asn Gly Thr Val Leu Val Glu Ser Phe Thr Leu Asp Gln Ile Ile Glu820 825 830Ser Ser Ser Ile Ile Tyr Glu His Asp Asp Ser Glu Thr Gln Glu Asp835 840 845Ser Phe Val Ile Lys Leu Thr Asp Gly Lys His Ser Val Glu Lys Thr850 855 860Val Leu Ile Ile Val Ile Pro Val Asp Asp Glu Thr Pro Arg Met Thr865 870 875 880Ile Asn Asn Gly Leu Glu Ile Glu Ile Gly Asp Thr Lys Ile Ile Asn885 890 895Asn Lys Ile Leu Met Ala Thr Asp Leu Asp Ser Glu Asp Lys Ser Leu900 905 910Val Tyr Ile Ile Arg Tyr Gly Pro Gly His Gly Leu Leu Gln Arg Arg915 920 925Lys Pro Thr Gly Ala Phe Glu Asn Ile Thr Leu Gly Met Asn Phe Thr930 935 940Gln Asp Glu Val Asp Arg Asn Leu Ile Gln Tyr Val His Leu Gly Gln945 950 955 960Glu Gly Ile Arg Asp Leu Ile Lys Phe Asp Val Thr Asp Gly Ile Asn965 970 975Pro Leu Ile Asp Arg Tyr Phe Tyr Val Ser Ile Gly Ser Ile Asp Ile980 985 990Val Phe Pro Asp Val Ile Ser Lys Gly Val Ser Leu Lys Glu Gly Gly995 10001005Lys Val Thr Leu Thr Thr Asp Leu Leu Ser Thr Ser Asp Leu Asn Ser101010151020Pro Asp Glu Asn Leu Val Phe Thr Ile Thr Arg Ala Pro Met Arg Gly1025103010351040His Leu Glu Cys Thr Asp Gln Pro Gly Val Ser Ile Thr Ser Phe Thr104510501055Gln Leu Gln Leu Ala Gly Asn Lys Ile Tyr Tyr Ile His Thr Ala Asp106010651070Asp Glu Val Lys Met Asp Ser Phe Glu Phe Gln Val Thr Asp Gly Arg107510801085Asn Pro Val Phe Arg Thr Phe Arg Ile Ser Ile Ser Asp Val Asp Asn109010951100Lys Lys Pro Val Val Thr Ile His Lys Leu Val Val Ser Glu Ser Glu1105111011151120Asn Lys Leu Ile Thr Pro Phe Glu Leu Thr Val Glu Asp Arg Asp Thr112511301135Pro Asp Ly s Leu Leu Lys Phe Thr Ile Thr Gln Val Pro Ile His Gly114011451150His Leu Leu Phe Asn Asn Thr Arg Pro Val Met Val Phe Thr Lys Gln115511601165Asp Leu Asn Glu Asn Leu Ile Ser Tyr Lys His Asp Gly Thr Glu Ser117011751180Ser Glu Asp Ser Phe Ser Phe Thr Val Thr Asp Gly Thr His Thr Asp1185119011951200Phe Tyr Val Phe Pro Asp Thr Val Phe Glu Thr Arg Arg Pro Gln Val120512101215Met Lys Ile Gln Val Leu Ala Val Asp Asn Ser Val Pro Gln Ile Ala122012251230Val Asn Lys Gly Ala Ser Thr Leu Arg Thr Leu Ala Thr Gly His Leu123512401245Gly Phe Met Ile Thr Ser Lys Ile Leu Lys Val Glu Asp Arg Asp Ser125012551260Leu His Ile Ser Leu Arg Phe Ile Val Thr Glu Ala Pro Gln His Gly1265127012751280Tyr Leu Leu Asn Leu Asp Lys Gly Asn His Ser Ile Thr Gln Phe Thr128512901295Gln Ala Asp Ile Asp Asp Met Lys Ile Cys Tyr Val Leu Arg Glu Gly130013051310Ala Asn Ala Thr Ser Asp Met Phe Tyr Phe Ala Val Glu Asp Gly Gly131513201325Lys Tyr Ser Pro Leu Leu Val Val Thr Ala Arg Arg Asp Ala Phe Leu133013351340Gly Cys Ser Leu Met Thr Leu Leu Gln Glu Val Phe Ile Lys134513501355<210>80<211>3105<212>PRT<213>人(Homo sapiens)<400>80Met Ala Arg Ser Trp Leu Thr Ala Thr Ser Thr Ser Arg Pro Ala Ala1 5 10 15Phe Gly Arg Ala Leu Leu Ser Pro Gly Leu Ala Gly Ala Ala Gly Val20 25 30Pro Ala Glu Glu Ala Ile Val Leu Ala Asn Arg Gly Leu Arg Val Pro35 40 45Phe Gly Arg Glu Val Trp Leu Asp Pro Leu His Asp Leu Val Leu Gln50 55 60Val Gln Pro Gly Asp Arg Cys Ala Val Ser Val Leu Asp Asn Asp Ala65 70 75 80Leu Ala Gln Arg Pro Gly Arg Leu Ser Pro Lys Arg Phe Pro Cys Asp85 90 95Phe Gly Pro Gly Glu Val Arg Tyr Ser His Leu Gly Ala Arg Ser Pro100 105 110Ser Arg Asp Arg Val Arg Leu Gln Leu Arg Tyr Asp Ala Pro Gly Gly115 120 125Ala Val Val Leu Pro Leu Val Leu Glu Val Glu Val Val Phe Thr Gln130 135 140Leu Glu Val Val Thr Arg Asn Leu Pro Leu Val Val Glu Glu Leu Leu145 150 155 160Gly Thr Ser Asn Ala Leu Asp Ala Arg Ser Leu Glu Phe Ala Phe Gln165 170 175Pro Glu Thr Glu Glu Cys Arg Val Gly Ile Leu Ser Gly Leu Gly Ala180 185 190Leu Pro Arg Tyr Gly Glu Leu Leu His Tyr Pro Gln Val Pro Gly Gly195 200 205Ala Arg Glu Gly Gly Ala Pro Glu Thr Leu Leu Met Asp Cys Lys Ala210 215 220Phe Gln Glu Leu Gly Val Arg Tyr Arg His Thr Ala Ala Ser Arg Ser225 230 235 240Pro Asn Arg Asp Trp Ile Pro Met Val Val Glu Leu Arg Ser Arg Gly245 250 255Ala Pro Val Gly Ser Pro Ala Leu Lys Arg Glu His Phe Gln Val Leu260 265 270Val Arg Ile Arg Gly Gly Ala Glu Asn Thr Ala Pro Lys Pro Ser Phe275 280 285Val Ala Met Met Met Met Glu Val Asp Gln Phe Val Leu Thr Ala Leu290 295 300Thr Pro Asp Met Leu Ala Ala Glu Asp Ala Glu Ser Pro Ser Asp Leu305 310 315 320Leu Ile Phe Asn Leu Thr Ser Pro Phe Gln Pro Gly Gln Gly Tyr Leu325 330 335Val Ser Thr Asp Asp Arg Ser Leu Pro Leu Ser Ser Phe Thr Gln Arg340 345 350Asp Leu Arg Leu Leu Lys Ile Ala Tyr Gln Pro Pro Ser Glu Asp Ser355 360 365Asp Gln Glu Arg Leu Phe Glu Leu Glu Leu Glu Val Val Asp Leu Glu370 375 380Gly Ala Ala Ser Asp Pro Phe Ala Phe Met Val Val Val Lys Pro Met385 390 395 400Asn Thr Met Ala Pro Val Val Thr Arg Asn Thr Gly Leu Ile Leu Tyr405 410 4l5Glu Gly Gln Ser Arg Pro Leu Thr Gly Pro Ala Gly Ser Gly Pro Gln420 425 430Asn Leu Val Ile Ser Asp Glu Asp Asp Leu Glu Ala Val Arg Leu Glu435 440 445Val Val Ala Gly Leu Arg His Gly His Leu Val Ile Leu Gly Ala Ser450 455 460Ser Gly Ser Ser Ala Pro Lys Ser Phe Thr Val Ala Glu Leu Ala Ala465 470 475 480Gly Gln Val Val Tyr Gln His Asp Asp Arg Asp Gly Ser Leu Ser Asp485 490 495Asn Leu Val Leu Arg Met Val Asp Gly Gly Gly Arg His Gln Val Gln500 505 510Phe Leu Phe Pro Ile Thr Leu Val Pro Val Asp Asp Gln Pro Pro Val515 520 525Leu Asn Ala Asn Thr Gly Leu Thr Leu Ala Glu Gly Glu Thr Val Pro530 535 540Ile Leu Pro Leu Ser Leu Ser Ala Thr Asp Met Asp Ser Asp Asp Ser545 550 555 560Leu Leu Leu Phe Val Leu Glu Ser Pro Phe Leu Thr Thr Gly His Leu565 570 575Leu Leu Arg Gln Thr His Pro Pro His Glu Lys Gln Glu Leu Leu Arg580 585 590Gly Leu Trp Arg Lys Glu Gly Ala Phe Tyr Glu Arg Thr Val Thr Glu595 600 605Trp Gln Gln Gln Asp Ile Thr Glu Gly Arg Leu Phe Tyr Arg His Ser6l0 615 620Gly Pro His Ser Pro Gly Pro Val Thr Asp Gln Phe Thr Phe Arg Val625 630 635 640Gln Asp Asn His Asp Pro Pro Asn Gln Ser Gly Leu Gln Arg Phe Val645 650 655Ile Arg Ile His Pro Val Asp Arg Leu Pro Pro Glu Leu Gly Ser Gly660 665 670Cys Pro Leu Arg Met Val Val Gln Glu Ser Gln Leu Thr Pro Leu Arg675 680 685Lys Lys Trp Leu Arg Tyr Thr Asp Leu Asp Thr Asp Asp Arg Glu Leu690 695 700Arg Tyr Thr Val Thr Gln Pro Pro Thr Asp Thr Asp Glu Asn His Leu705 710 715 720Pro Ala Pro Leu Gly Thr Leu Val Leu Thr Asp Asn Pro Ser Val Val725 730 735Val Thr His Phe Thr Gln Ala Gln Ile Asn His His Lys Ile Ala Tyr740 745 750Arg Pro Pro Gly Gln Glu Leu Gly Val Ala Thr Arg Val Ala Gln Phe755 760 765Gln Phe Gln Val Glu Asp Arg Ala Gly Asn Val Ala Pro Gly Thr Phe770 775 780Thr Leu Tyr Leu His Pro Val Asp Asn Gln Pro Pro Glu Ile Leu Asn785 790 795 800Thr Gly Phe Thr Ile Gln Glu Lys Gly His His Ile Leu Ser Glu Thr805 810 815Glu Leu His Val Asn Asp Val Asp Thr Asp Val Ala His Ile Ser Phe820 825 830Thr Leu Thr Gln Ala Pro Lys His Gly His Met Arg Val Ser Gly Gln835 840 845Ile Leu His Val Gly Gly Leu Phe His Leu Glu Asp Ile Lys Gln Gly850 855 860Arg Val Ser Tyr Ala His Asn Gly Asp Lys Ser Leu Thr Asp Ser Cys865 870 875 880Ser Leu Glu Val Ser Asp Arg His His Val Val Pro Ile Thr Leu Arg885 890 895Val Asn Val Arg Pro Val Asp Asp Glu Val Pro Ile Leu Ser His Pro900 905 910Thr Gly Thr Leu Glu Ser Tyr Leu Asp Val Leu Glu Asn Gly Ala Thr915 920 925Glu Ile Thr Ala Asn Val Ile Lys Gly Thr Asn Glu Glu Thr Asp Asp930 935 940Leu Met Leu Thr Phe Leu Leu Glu Asp Pro Pro Leu Tyr Gly Glu Ile945 950 955 960Leu Val Asn Gly Ile Pro Ala Glu Gln Phe Thr Gln Arg Asp Ile Leu965 970 975Glu Gly Ser Val Val Tyr Thr His Thr Ser Gly Glu Ile Gly Leu Leu980 985 990Pro Lys Ala Asp Ser Phe Asn Leu Ser Leu Ser Asp Lys Ser Gln Glu995 10001005Trp Arg Ile Gly Gly Asn Thr Ile Gln Gly Val Thr Ile Trp Val Thr101010151020Ile Leu Pro Val Asp Ser Gln Ala Pro Glu Ile Ser Val Gly Glu Glnl025103010351040Leu Ile Val Met Glu Gly Asp Lys Ser Val Ile Thr Ser Val His Ile104510501055Ser Ala Glu Asp Val Asp Ser Leu Asn Asp Asp Ile Leu Cys Thr Ile106010651070Val Ile Gln Pro Thr Ser Gly Tyr Val Glu Asn Ile Ser Pro Ala Pro107510801085Gly Ser Glu Lys Ser Arg Ala Gly Ile Ala Ile Ser Ala Phe Asn Leu109010951100Lys Asp Leu Arg Gln Gly His Ile Asn Tyr Val Gln Ser Val His Lys1105111011151120Gly Val Glu Pro Val Glu Asp Arg Phe Val Phe Arg Cys Ser Asp Gly112511301135Ile Asn Phe Ser Glu Arg Gln Phe Phe Pro Ile Val Ile Ile Pro Thr114011451150Asn Asp Glu Gln Pro Glu Met Phe Met Arg Glu Phe Met Val Met Glu115511601165Gly Met Ser Leu Val Ile Asp Thr Pro Ile Leu Asn Ala Ala Asp Ala117011751180Asp Val Pro Leu Asp Asp Leu Thr Phe Thr Ile Thr Gln Phe Pro Thr1185119011951200His Gly His Ile Met Asn Gln Leu Ile Asn Gly Thr Val Leu Val Glu120512101215Ser Phe Thr Leu Asp Gln Ile Ile Glu Ser Ser Ser Ile Ile Tyr Glu122012251230His Asp Asp Ser Glu Thr Gln Glu Asp Ser Phe Val Ile Lys Leu Thr123512401245Asp Gly Lys His Ser Val Glu Lys Thr Val Leu Ile Ile Val Ile Pro125012551260Val Asp Asp Glu Thr Pro Arg Met Thr Ile Asn Asn Gly Leu Glu Ile1265127012751280Glu Ile Gly Asp Thr Lys Ile Ile Asn Asn Lys Ile Leu Met Ala Thr128512901295Asp Leu Asp Ser Glu Asp Lys Ser Leu Val Tyr Ile Ile Arg Tyr Gly130013051310Pro Gly His Gly Leu Leu Gln Arg Arg Lys Pro Thr Gly Ala Phe Glu131513201325Asn Ile Thr Leu Gly Met Asn Phe Thr Gln Asp Glu Val Asp Arg Asn133013351340Leu Ile Gln Tyr Val His Leu Gly Gln Glu Gly Ile Arg Asp Leu Ile1345135013551360Lys Phe Asp Val Thr Asp Gly Ile Asn Pro Leu Ile Asp Arg Tyr Phe136513701375Tyr Val Ser Ile Gly Ser Ile Asp Ile Val Phe Pro Asp Val Ile Ser138013851390Lys Gly Val Ser Leu Lys Glu Gly Gly Lys Val Thr Leu Thr Thr Asp139514001405Leu Leu Ser Thr Ser Asp Leu Asn Ser Pro Asp Glu Asn Leu Val Phe141014151420Thr Ile Thr Arg Ala Pro Met Arg Gly His Leu Glu Cys ThrAsp Gln1425143014351440Pro Gly Val Ser Ile Thr Ser Phe Thr Gln Leu Gln Leu Ala Gly Asn144514501455Lys Ile Tyr Tyr Ile His Thr Ala Asp Asp Glu Val Lys Met Asp Ser146014651470Phe Glu Phe Gln Val Thr Asp Gly Arg Asn Pro Val Phe Arg Thr Phe147514801485Arg Ile Ser Ile Ser Asp Val Asp Asn Lys Lys Pro Val Val Thr Ilel49014951500His Lys Leu Val Val Ser Glu Ser Glu Asn Lys Leu Ile Thr Pro Phe1505151015151520Glu Leu Thr Val Glu Asp Arg Asp Thr Pro Asp Lys Leu Leu Lys Phe152515301535Thr Ile Thr Gln Val Pro Ile His Gly His Leu Leu Phe Asn Asn Thr154015451550Arg Pro Val Met Val Phe Thr Lys Gln Asp Leu Asn Glu Asn Leu Ile155515601565Ser Tyr Lys His Asp Gly Thr Glu Ser Ser Glu Asp Ser Phe Ser Phe157015751580Thr Val Thr Asp Gly Thr His Thr Asp Phe Tyr Val Phe Pro Asp Thr1585159015951600Val Phe Glu Thr Arg Arg Pro Gln Val Met Lys Ile Gln Val Leu Ala160516101615Val Asp Asn Ser Val Pro Gln Ile Ala Val Asn Lys Gly Ala Ser Thr162016251630Leu Arg Thr Leu Ala Thr Gly His Leu Gly Phe Met Ile Thr Ser Lys163516401645Ile Leu Lys Val Glu Asp Arg Asp Ser Leu His Ile Ser Leu Arg Phe165016551660Ile Val Thr Glu Ala Pro Gln His Gly Tyr Leu Leu Asn Leu Asp Lys1665167016751680Gly Asn His Ser Ile Thr Gln Phe Thr Gln Ala Asp Ile Asp Asp Met168516901695Lys Ile Cys Tyr Val Leu Arg Glu Gly Ala Asn Ala Thr Ser Asp Met170017051710Phe Tyr Phe Ala Val Glu Asp Gly Gly Gly Asn Lys Leu Thr Tyr Gln171517201725Asn Phe Arg Leu Asn Trp Ala Trp Ile Ser Phe Glu Lys Glu Tyr Tyr173017351740Leu Val Asn Glu Asp Ser Lys Phe Leu Asp Val Val Leu Lys Arg Arg1745175017551760Gly Tyr Leu Gly Glu Thr Ser Phe Ile Ser Ile Gly Thr Arg Asp Arg176517701775Thr Ala Glu Lys Asp Lys Asp Phe Lys Gly Lys Ala Gln Lys Gln Val178017851790Gln Phe Asn Pro Gly Gln Thr Arg Ala Thr Trp Arg Val Arg Ile Leu179518001805Ser Asp Gly Glu His Glu Gln Ser Glu Thr Phe Gln Val Val Leu Ser181018151820Glu Pro Val Leu Ala Ala Leu Glu Phe Pro Thr Val Ala Thr Val Glu1825183018351840Ile Val Asp Pro Gly Asp Glu Pro Thr Val Phe Ile Pro Gln Ser Lys184518501855Tyr Ser Val Glu Glu Asp Val Gly Glu Leu Phe Ile Pro Ile Arg Arg186018651870Ser Gly Asp Val Ser Gln Glu Leu Met Val Val Cys Tyr Thr Gln Gln187518801885Gly Thr Ala Thr Gly Thr Val Pro Thr Ser Val Leu Ser Tyr Ser Asp189018951900Tyr Ile Ser Arg Pro Glu Asp His Thr Ser Val Val Arg Phe Asp Lys1905191019151920Asp Glu Arg Glu Lys Leu Cys Arg Ile Val Ile Ile Asp Asp Ser Leu192519301935Tyr Glu Glu Glu Glu Thr Phe His Val Leu Leu Ser Met Pro Met Gly194019451950Gly Arg Ile Gly Ser Glu Phe Pro Gly Ala Gln Val Thr Ile Val Pro195519601965Asp Lys Asp Asp Gly Pro Ser Asp Ser Lys Phe Asn Val Ala Glu Asn197019751980Tyr Ser Leu Leu Pro Phe Thr Cys Phe Gln Gly Ser Ile Ala Thr Ala1985199019952000Glu Ala Ala Thr Gln Gly Gly Gly Arg Ser Thr Arg Gln Val Ala Ala200520102015Val Lys Lys Asp Lys Asp Phe Lys Gly Lys Ala Gln Lys Gln Val Gln202020252030Phe Asn Pro Gly Gln Thr Arg Ala Thr Trp Arg Val Arg Ile Leu Ser203520402045Asp Gly Glu His Glu Gln Ser Glu Thr Phe Gln Val Val Leu Ser Glu205020552060Pro Val Leu Ala Ala Leu Glu Phe Pro Thr Val Ala Thr Val Glu Ile2065207020752080Val Asp Pro Gly Asp Ala Cys Pro Trp Gly Glu Glu Ser Asp Gln Ser208520902095Ser Gln Gly Leu Lys Leu Gln Ser Phe Leu Thr Lys Met Met Val Ser210021052110Thr Asn Leu Leu Glu Asn Ser Phe Ser Arg Glu Asp Gln His Gln Glu211521202125Gln Leu Ser Arg Gln Lys Lys Trp Glu Ser Lys Thr Met Ile Ile Tyr213021352140Thr Phe Ile Leu Cys Glu Thr Glu Lys Pro Cys Ile Leu Glu Leu Met214521502155 2160Asp Asp Val Leu Tyr Glu Glu Val Glu Glu Leu Arg Leu Val Leu Gly216521702175Thr Pro Gln Ser Asn Ser Pro Phe Gly Ala Ala Val Gly Glu Gln Asn218021852190Glu Thr Leu Ile Arg Ile Arg Asp Asp Ala Asp Lys Thr Val Ile Lys219522002205Phe Gly Glu Thr Lys Phe Ser Val Thr Glu Pro Lys Glu Pro Gly Glu221022152220Ser Val Val Ile Arg Ile Pro Val Ile Arg Gln Gly Asp Thr Ser Lys2225223022352240Val Ser Ile Val Arg Val His Thr Lys Asp Gly Ser Ala Thr Ser Gly224522502255Glu Asp Tyr His Pro Val Ser Glu Glu Ile Glu Phe Lys Glu Gly Glu226022652270Thr Gln His Val Val Glu Ile Glu Val Thr Phe Asp Gly Val Arg Glu227522802285Met Arg Glu Ala Phe Thr Val His Leu Lys Pro Asp Glu Asn Met Ile229022952300Ala Glu Met Gln Leu Ser Asn Phe Glu Leu Thr Leu Ser Pro Asp Gly2305231023152320Thr Arg Val Gly Asn His Lys Cys Ser Asn Leu Leu Asp Tyr Thr Glu232523302335Val Lys Thr His Tyr Gly Phe Leu Thr Asp Ala Thr Lys Asn Pro Glu234023452350Ile Ile Gly Glu Thr Tyr Pro Tyr Gln Tyr Ser Leu Ser Ile Arg Gly235523602365Ser Thr Thr Leu Arg Phe Tyr Arg Asn Leu Asn Leu Glu Ala Cys Leu237023752380Trp Glu Phe Val Ser Tyr Tyr Asp Met Ser Glu Leu Leu Ala Asp Cys2385239023952400Arg Ser Val Leu Asn Ala Ser Ile Phe His Glu Met Ala Pro Glu Gly240524102415Lys Gln Ser Lys Cys Leu Val Asn Ser Thr Leu Tyr Ser Ile Leu Glu242024252430Cys His Glu Ser Leu Pro Asn Phe Cys Ile Ser Ala Leu Arg Met Gly243524402445Lys Trp Arg Lys Ile Lys Ser Lys Pro Ser Ala Gln Thr Pro Cys Ala245024552460Gln Arg Leu Arg Gly Phe Ile Asp His Pro Arg Lys Gln Pro Leu Gln2465247024752480Gln Ala Ser Ala Asp Pro Gly Met Leu Pro Val Ile Ser Thr Arg Glu248524902495Leu Ser Asn Phe Glu Leu Thr Leu Ser Pro Asp Gly Thr Arg Val Gly250025052510Asn His Lys Cys Ser Asn Leu Leu Asp Tyr Thr Glu Val Lys Thr His251525202525Tyr Gly Phe Leu Thr Asp Ala Thr Lys Asn Pro Glu Ile Ile Gly Glu253025352540Thr Tyr Pro Tyr Gln Tyr Ser Leu Ser Ile Arg Gly Ser Thr Thr Leu2545255025552560Arg Phe Tyr Arg Asn Leu Asn Leu Glu Ala Cys Leu Trp Glu Phe Val256525702575Ser Tyr Tyr Asp Met Ser Glu Leu Leu Ala Asp Cys Gly Gly Thr Ile258025852590Gly Thr Asp Gly Gln Val Leu Asn Leu Val Gln Ser Tyr Val Thr Leu259526002605Arg Val Pro Leu Tyr Val Ser Tyr Val Phe His Ser Pro Val Gly Val261026152620Gly Gly Trp Gln His Phe Asp Leu Lys Ser Glu Leu Arg Leu Thr Phe2625263026352640Val Tyr Asp Thr Ala Ile Leu Trp Asn Asp Gly Ile Gly Ser Pro Pro264526502655Glu Ala Glu Leu Gln Gly Ser Leu Tyr Pro Thr Ser Met Arg Ile Gly266026652670Asp Glu Gly Arg Leu Ala Val His Phe Lys Thr Glu Ala Gln Phe His267526802685Gly Leu Phe Val Leu Ser His Pro Ala Ser Phe Thr Ser Ser Val Ile269026952700Met Ser Ala Asp His Pro Gly Leu Thr Phe Ser Leu Arg Leu Ile Arg2705271027152720Ser Glu Pro Thr Tyr Asn Gln Pro Val Gln Gln Trp Ser Phe Val Ser272527302735Asp Phe Ala Val Arg Asp Tyr Ser Gly Thr Tyr Thr Val Lys Leu Val274027452750Pro Cys Thr Ala Pro Ser His Gln Glu Tyr Arg Leu Pro Val Thr Cys275527602765Asn Pro Arg Glu Pro Val Thr Phe Asp Leu Asp Ile Arg Phe Gln Gln277027752780Val Ser Asp Pro Val Ala Ala Glu Phe Ser Leu Asn Thr Gln Met Tyr2785279027952800Leu Leu Ser Lys Lys Ser Leu Trp Leu Ser Asp Gly Ser Met Gly Phe280528102815Gly Gln Glu Ser Asp Val Ala Phe Ala Glu Gly Asp Ile Ile Tyr Gly282028252830Arg Val Met Val Asp Pro Val Gln Asn Leu Gly Asp Ser Phe Tyr Cys283528402845Ser Ile Glu Lys Val Phe Leu Cys Thr Gly Ala Asp Gly Tyr Val Pro285028552860Lys Tyr Ser Pro Met Asn Ala Glu Tyr Gly Cys Leu Ala Asp Ser Pro2865287028752880Ser Leu Leu Tyr Arg Phe Lys Ile Val Asp Lys Ala Gln Pro Glu Thr288528902895Gln Ala Thr Ser Phe Gly Asn Val Leu Phe Asn Ala Lys Leu Ala Val290029052910Asp Asp Pro Glu Ala Ile Leu Leu Val Asn Gln Pro Gly Ser Asp Gly291529202925Phe Lys Val Asp Ser Thr Pro Leu Phe Gln Val Ala Leu Gly Arg Glu293029352940Trp Tyr Ile His Thr Ile Tyr Thr Val Arg Ser Lys Asp Asn Ala Asn2945295029552960Arg Gly Ile Gly Lys Arg Ser Val Glu Tyr His Ser Leu Val Ser Gln296529702975Gly Lys Pro Gln Ser Thr Thr Lys Ser Arg Lys Lys Arg Glu Ile Arg298029852990Ser Thr Pro Ser Leu Ala Trp Glu Ile Gly Ala Glu Asn Ser Arg Gly299530003005Thr Asn Ile Gln His Ile Ala Leu Asp Arg Thr Lys Arg Gln Ile Pro301030153020His Gly Arg Ala Pro Pro Asp Gly Ile Leu Pro Trp Glu Leu Asn Ser3025303030353040Pro Ser Ser Ala Val Ser Leu Val Thr Val Val Gly Gly Thr Thr Val304530503055Gly Leu Leu Thr Ile Cys Leu Thr Val Ile Ala Val Leu Met Cys Arg306030653070Gly Lys Glu Ser Phe Arg Gly Lys Asp Ala Pro Lys Gly Ser Ser Ser307530803085Ser Glu Pro Met Val Pro Pro Gln Ser His His Asn Asp Ser Ser Glu309030953100Val3105<210>81<211>457<212>PRT<213>人(Homo sapiens)<400>81Met Gly Cys Ser Gly Ala Trp Gly Leu Ser Cys Pro Cys Pro Gln Thr1 5 10 15Pro Ser Trp Ala Trp Arg Lys Met Arg Thr Pro Ser Met Arg Asn Arg20 25 30Ser Gly Ala Val Trp Ser Arg Ala Ser Val Pro Phe Ser Ala Trp Glu35 40 45Val Glu Val Gln Met Arg Val Thr Gly Leu Gly Arg Arg Gly Ala Gln50 55 60Gly Met Ala Val Trp Tyr Thr Arg Gly Arg Gly His Val Gly Ser Val65 70 75 80Leu Gly Gly Leu Ala Ser Trp Asp Gly Ile Gly Ile Phe Phe Asp Ser85 90 95Pro Ala Glu Asp Thr Gln Asp Ser Pro Ala Ile Arg Val Leu Ala Ser100 105 110Asp Gly His Ile Pro Ser Glu Gln Pro Gly Asp Gly Ala Ser Gln Gly115 120 125Leu Gly Ser Cys His Trp Asp Phe Arg Asn Arg Pro His Pro Phe Arg130 135 140Ala Arg Ile Thr Tyr Trp Gly Gln Arg Leu Arg Met Ser Leu Asn Ser145 150 155 160Gly Leu Thr Pro Ser Asp Pro Gly Glu Phe Cys Val Asp Val Gly Pro165 170 175Leu Leu Leu Val Pro Gly Gly Phe Phe Gly Val Ser Ala Ala Thr Gly180 185 190Thr Leu Ala Asp Asp His Asp Val Leu Ser Phe Leu Thr Phe Ser Leu195 200 205Ser Glu Pro Ser Pro Glu Val Pro Pro Gln Pro Phe Leu Glu Met Gln210 215 220His Val Arg Leu Ala Arg Gln Leu Glu Gly Leu Trp Ala Arg Leu Gly225 230 235 240Leu Gly Thr Arg Glu Asp Val Thr Pro Lys Ser Asp Ser Glu Ala Gln245 250 255Gly Glu Gly Glu Arg Leu Phe Asp Leu Glu Glu Thr Leu Gly Arg His260 265 270Arg Arg Ile Leu Gln Ala Leu Arg Gly Leu Ser Lys Gln Leu Ala Gln275 280 285Ala Glu Arg Gln Trp Lys Lys Gln Leu Gly Pro Gln Ala Lys Pro Gly290 295 300Leu Thr Glu Ala Gly Asp Ala Ala Val Arg Met Ala Ala Glu Ala Gln305 310 315 320Val Ser Tyr Leu Pro Val Gly Ile Glu His His Phe Leu Glu Leu Asp325 330 335His Ile Leu Gly Leu Leu Gln Glu Glu Leu Arg Gly Pro Ala Lys Ala340 345 350Ala Ala Lys Ala Pro Arg Pro Pro Gly Gln Pro Pro Arg Ala Ser Ser355 360 365Cys Leu Gln Pro Gly Ile Phe Leu Phe Tyr Leu Leu Ile Gln Thr Val370 375 380Gly Phe Phe Gly Tyr Val His Phe Arg Arg Pro Val Pro Arg Pro Ala385 390 395 400Lys Thr Met Ala Phe Met Val Lys Thr Met Val Gly Gly Gln Leu Lys405 410 415Asn Leu Thr Gly Ser Leu Gly Gly Gly Glu Asp Lys Gly Asp Gly Asp420 425 430Lys Ser Ala Ala Glu Ala Gln Gly Met Ser Arg Glu Glu Tyr Glu Glu435 440 445Tyr Gln Lys Gln Leu Val Glu Glu Lys450 455<210>82<211>526<212>PRT<213>人(Homo sapiens)<400>82Met Pro Ala Val Ser Gly Pro Gly Pro Leu Phe Cys Leu Leu Leu Leu1 5 10 15Leu Leu Asp Pro His Ser Pro Glu Thr Gly Cys Pro Pro Leu Arg Arg20 25 30Phe Glu Tyr Lys Leu Ser Phe Lys Gly Pro Arg Leu Ala Leu Pro Gly35 40 45Ala Gly Ile Pro Phe Trp Ser His His Gly Asp Ala Ile Leu Gly Leu50 55 60Glu Glu Val Arg Leu Thr Pro Ser Met Arg Asn Arg Ser Gly Ala Val65 70 75 80Trp Ser Arg Ala Ser Val Pro Phe Ser Ala Trp Glu Val Glu Val Gln85 90 95Met Arg Val Thr Gly Leu Gly Arg Arg Gly Ala Gln Gly Met Ala Val100 105 110Trp Tyr Thr Arg Gly Arg Gly His Val Gly Ser Val Leu Gly Gly Leu115 120 125Ala Ser Trp Asp Gly Ile Gly Ile Phe Phe Asp Ser Pro Ala Glu Asp130 135 140Thr Gln Asp Ser Pro Ala Ile Arg Val Leu Ala Ser Asp Gly His Ile145 150 155 160Pro Ser Glu Gln Pro Gly Asp Gly Ala Ser Gln Gly Leu Gly Ser Cys165 170 175His Trp Asp Phe Arg Asn Arg Pro His Pro Phe Arg Ala Arg Ile Thr180 185 190Tyr Trp Gly Gln Arg Leu Arg Met Ser Leu Asn Ser Gly Leu Thr Pro195 200 205Ser Asp Pro Gly Glu Phe Cys Val Asp Val Gly Pro Leu Leu Leu Val210 215 220Pro Gly Gly Phe Phe Gly Val Ser Ala Ala Thr Gly Thr Leu Ala Asp225 230 235 240Asp His Asp Val Leu Ser Phe Leu Thr Phe Ser Leu Ser Glu Pro Ser245 250 255Pro Glu Val Pro Pro Gln Pro Phe Leu Glu Met Gln His Val Arg Leu260 265 270Ala Arg Gln Leu Glu Gly Leu Trp Ala Arg Leu Gly Leu Gly Thr Arg275 280 285Glu Asp Val Thr Pro Lys Ser Asp Ser Glu Ala Gln Gly Glu Gly Glu290 295 300Arg Leu Phe Asp Leu Glu Glu Thr Leu Gly Arg His Arg Arg Ile Leu305 310 315 320Gln Ala Leu Arg Gly Leu Ser Lys Gln Leu Ala Gln Ala Glu Arg Gln325 330 335Trp Lys Lys Gln Leu Gly Pro Pro Gly Gln Ala Arg Pro Asp Gly Gly340 345 350Trp Ala Leu Asp Ala Ser Cys Gln Ile Pro Ser Thr Pro Gly Arg Gly355 360 365Gly His Leu Ser Met Ser Leu Asn Lys Asp Ser Ala Lys Val Gly Ala370 375 380Leu Leu His Gly Gln Trp Thr Leu Leu Gln Ala Leu Gln Glu Met Arg385 390 395 400Asp Ala Ala Val Arg Met Ala Ala Glu Ala Gln Val Ser Tyr Leu Pro405 410 415Val Gly Ile Glu His His Phe Leu Glu Leu Asp His Ile Leu Gly Leu420 425 430Leu Gln Glu Glu Leu Arg Gly Pro Ala Lys Ala Ala Ala Lys Ala Pro435 440 445Arg Pro Pro Gly Gln Pro Pro Arg Ala Ser Ser Cys Leu Gln Pro Gly450 455 460Ile Phe Leu Phe Tyr Leu Leu Ile Gln Thr Val Gly Phe Phe Gly Tyr465 470 475 480Val His Phe Arg Gln Glu Leu Asn Lys Ser Leu Gln Glu Cys Leu Ser485 490 495Thr Gly Ser Leu Pro Leu Gly Pro Ala Pro His Thr Pro Arg Ala Leu500 505 510Gly Ile Leu Arg Arg Gln Pro Leu Pro Ala Ser Met Pro Ala515 520 525<210>83<211>904<212>PRT<213>人(Homo sapiens)<400>83Met Leu Leu Ala Leu Cys Ser Ser Leu Ala Leu Ile Phe Ala Ala Pro1 5 10 15Val Ser Gly Gln Leu Glu His Ser Gly Asn Tyr Tyr Cys Thr Ala Asp20 25 30Asn Gly Phe Gly Pro Gln His Ser Glu Val Val Ser Leu Ser Val Thr35 40 45Val Pro Val Ser His Pro Val Leu Thr Leu Ser Ser Ala Glu Ala Leu50 55 60Thr Phe Glu Gly Ala Thr Val Thr Leu His Ser Ser Leu Ile Leu Gln65 70 75 80Ala Pro Leu Ser Val Phe Glu Gly Asp Phe Val Val Leu Arg Cys Arg85 90 95Ala Lys Ala Glu Val Thr Leu Asn Thr Met Tyr Lys Asn Gly Asn Val100 105 110Leu Thr Phe Leu Asn Lys Ser Ser Asp Phe His Ile His His Ala Ser115 120 125Leu Lys Asp Asn Gly Ala Tyr His Phe Thr Gly Phe Asn Gly Ser Asn130 135 140Phe Ser Val Ser Ser Asn Ile Val Lys Ile Gln Val Gln Glu His Leu145 150 155 160Leu Pro Gln Trp Phe Leu Lys Ala Pro Asp Pro Thr Val Ala Leu Ser165 170 175Glu Ile Phe Ser Val Asn Arg Gly Pro Leu Leu Thr Gly Thr Gly Ser180 185 190Arg Val Met Thr Pro Trp Ile Tyr Phe Pro Thr Glu Asp Trp Asn Phe195 200 205Thr Leu Ile Pro Ile Thr Val Asp Asp Ala Cys Lys Arg Pro Cys Ala210 215 220Pro Arg Ala Pro Trp Glu Val Gly Ser Leu Thr Pro Gly Lys Ser Phe225 230 235 240Gln Gln Lys Gly Asn Pro Asp Leu Leu Met Gly Pro Phe Asp Val Leu245 250 255His Leu Ser Leu Ile Thr Leu Phe Cys Asn Met Ala Gly Ser Leu Phe260 265 270Tyr Tyr Met Glu Leu Gly Glu Lys Lys Asp Ala Leu Phe Val Thr Gly275 280 285Asn Glu Ser Arg Ser Tyr His Trp Phe Gln Lys Phe Ser Leu Ala Gly290 295 300Gly Gln Glu Ala Asp Gln Lys Leu Trp Phe Pro Pro Gly Leu Met Ser305 310 315 320Gln Asp Ile Phe Ile Tyr Ile Arg Gln Gly Glu Ser Cys Leu Val Ile325 330 335Glu Met Phe His Gln Val Tyr Arg Arg Pro Ala Gly Gly Val Pro Val340 345 350Glu His Met Ser Val Trp Ala Leu Arg Val Asn Ser Ser Gly Leu Phe355 360 365Ala Tyr Ala Asp Gly Trp Leu Phe Thr Leu Phe Gln Leu Gln Ser Val370 375 380Asp Asn Leu Ser Pro Ser Thr Gln Ser Gln Thr His Glu Gly His Glu385 390 395 400Lys Leu Cys Pro Phe Leu Ala Ile Gly Pro Pro Ala His Ser Arg Gly405 410 415Ser Phe Leu Arg Ala Lys Lys Ser Leu Val Ala Tyr Ile Lys Gly Asn420 425 430Gln Leu Ser Phe Pro Pro Val Glu Asp Leu Leu Pro Lys Ser Gln Trp435 440 445Pro Cys Ile Gln Val Leu Pro Arg Asn Ile Ala Ala Ala Ala His Lys450 455 460Pro Val Ile Ser Val His Pro Pro Trp Thr Thr Phe Phe Lys Gly Glu465 470 475 480Arg Val Thr Leu Thr Cys Asn Gly Phe Gln Phe Tyr Ala Thr Glu Lys485 490 495Thr Thr Trp Tyr His Arg His Tyr Trp Gly Glu Lys Leu Thr Leu Thr500 505 510Pro Gly Asn Thr Leu Glu Val Arg Glu Ser Gly Leu Tyr Arg Cys Gln515 520 525Ala Arg Gly Ser Pro Arg Ser Asn Pro Val Arg Leu Leu Phe Ser Ser530 535 540Gly Glu Lys Glu Asp Cys Val Ser Asp Lys Asn Pro Ala Thr Asn His545 550 555 560Thr Pro Met Ser Arg Lys Arg Ser Ser Cys Ser Ser Leu Ser Ala Thr565 570 575Ser Phe Ile Ala Pro Ala Leu Arg Leu Asp Ser Leu Ile Leu Gln Ala580 585 590Pro Tyr Ser Val Phe Glu Gly Asp Thr Leu Val Leu Arg Cys His Arg595 600 605Arg Arg Lys Glu Lys Leu Thr Ala Val Lys Tyr Thr Trp Asn Gly Asn610 615 620Ile Leu Ser Ile Ser Asn Lys Ser Trp Asp Leu Leu Ile Pro Gln Ala625 630 635 640Ser Ser Asn Asn Asn Gly Asn Tyr Arg Cys Ile Gly Tyr Gly Asp Glu645 650 655Asn Asp Val Phe Arg Ser Asn Phe Lys Ile Ile Lys Ile Gln Gly Ile660 665 670Pro Val Ser Gly Val Leu Leu Glu Thr Gln Pro Ser Gly Gly Gln Ala675 680 685Val Glu Gly Glu Met Leu Val Leu Val Cys Ser Val Ala Glu Gly Thr690 695 700Gly Asp Thr Thr Phe Ser Trp His Arg Glu Asp Met Gln Glu Ser Leu705 710 715 720Gly Arg Lys Thr Gln Arg Ser Leu Arg Ala Glu Leu Glu Leu Pro Ala725 730 735Ile Arg Gln Ser His Ala Gly Gly Tyr Tyr Cys Thr Ala Asp Asn Ser740 745 750Tyr Gly Pro Val Gln Ser Met Val Leu Asn Val Thr Val Arg Glu Thr755 760 765Pro Gly Asn Arg Asp Gly Leu Val Ala Ala Gly Ala Thr Gly Gly Leu770 775 780Leu Ser Ala Leu Leu Leu Ala Val Ala Leu Leu Phe His Cys Trp Arg785 790 795 800Arg Arg Lys Ser Val His Pro Lys Lys Gly Asp Leu Val Tyr Ser Glu805 810 815Ile Gln Thr Thr Gln Leu Gly Glu Glu Glu Glu Gly Asn His Gly Asn820 825 830Lys Asn Gln Glu Leu Glu Leu Val Asn Val Gly Glu Ser Phe Ser His835 840 845Arg Ala Cys Ile Trp Ser Thr Leu Met Gly Thr Cys Gln Thr Ile Gly850 855 860Gly Ala Asn Thr Ser Arg Thr Leu Leu Glu Asp Lys Asp Val Ser Val865 870 875 880Val Tyr Ser Glu Val Lys Thr Gln His Pro Asp Asn Ser Ala Gly Lys885 890 895Ile Ser Ser Lys Asp Glu Glu Ser900<210>84<211>515<212>PRT<213>人(Homo sapiens)<400>84Met Leu Leu Trp Ala Ser Leu Leu Ala Phe Ala Pro Val Cys Gly Gln1 5 10 15Ser Ala Ala Ala His Lys Pro Val Ile Ser Val His Pro Pro Trp Thr20 25 30Thr Phe Phe Lys Gly Glu Arg Val Thr Leu Thr Cys Asn Gly Phe Gln35 40 45Phe Tyr Ala Thr Glu Lys Thr Thr Trp Tyr His Arg His Tyr Trp Gly50 55 60Glu Lys Leu Thr Leu Thr Pro Gly Asn Thr Leu Glu Val Arg Glu Ser65 70 75 80Gly Leu Tyr Arg Cys Gln Ala Arg Gly Ser Pro Arg Ser Asn Pro Val85 90 95Arg Leu Leu Phe Ser Ser Asp Ser Leu Ile Leu Gln Ala Pro Tyr Ser100 105 110Val Phe Glu Gly Asp Thr Leu Val Leu Arg Cys His Arg Arg Arg Lys115 120 125Glu Lys Leu Thr Ala Val Lys Tyr Thr Trp Asn Gly Asn Ile Leu Ser130 135 140Ile Ser Asn Lys Ser Trp Asp Leu Leu Ile Pro Gln Ala Ser Ser Asn145 150 155 160Asn Asn Gly Asn Tyr Arg Cys Ile Gly Tyr Gly Asp Glu Asn Asp Val165 170 175Phe Arg Ser Asn Phe Lys Ile Ile Lys Ile Gln Glu Leu Phe Pro His180 185 190Pro Glu Leu Lys Ala Thr Asp Ser Gln Pro Thr Glu Gly Asn Ser Val195 200 205Asn Leu Ser Cys Glu Thr Gln Leu Pro Pro Glu Arg Ser Asp Thr Pro210 215 220Leu His Phe Asn Phe Phe Arg Asp Gly Glu Val Ile Leu Ser Asp Trp225 230 235 240Ser Thr Tyr Pro Glu Leu Gln Leu Pro Thr Val Trp Arg Glu Asn Ser245 250 255Gly Ser Tyr Trp Cys Gly Ala Glu Thr Val Arg Gly Asn Ile His Lys260 265 270His Ser Pro Ser Leu Gln Ile His Val Gln Arg Ile Pro Val Ser Gly275 280 285Val Leu Leu Glu Thr Gln Pro Ser Gly Gly Gln Ala Val Glu Gly Glu290 295 300Met Leu Val Leu Val Cys Ser Val Ala Glu Gly Thr Gly Asp Thr Thr305 310 315 320Phe Ser Trp His Arg Glu Asp Met Gln Glu Ser Leu Gly Arg Lys Thr325 330 335Gln Arg Ser Leu Arg Ala Glu Leu Glu Leu Pro Ala Ile Arg Gln Ser340 345 350His Ala Gly Gly Tyr Tyr Cys Thr Ala Asp Asn Ser Tyr Gly Pro Val355 360 365Gln Ser Met Val Leu Asn Val Thr Val Arg Glu Thr Pro Gly Asn Arg370 375 380Asp Gly Leu Val Ala Ala Gly Ala Thr Gly Gly Leu Leu Ser Ala Leu385 390 395 400Leu Leu Ala Val Ala Leu Leu Phe His Cys Trp Arg Arg Arg Lys Ser405 410 415Gly Val Gly Phe Leu Gly Asp Glu Thr Arg Leu Pro Pro Ala Pro Gly420 425 430Pro Gly Glu Ser Ser His Ser Ile Cys Pro Ala Gln Val Glu Leu Gln435 440 445Ser Leu Tyr Val Asp Val His Pro Lys Lys Gly Asp Leu Val Tyr Ser450 455 460Glu Ile Gln Thr Thr Gln Leu Gly Glu Glu Glu Glu Ala Asn Thr Ser465 470 475 480Arg Thr Leu Leu Glu Asp Lys Asp Val Ser Val Val Tyr Ser Glu Val485 490 495Lys Thr Gln His Pro Asp Asn Ser Ala Gly Lys Ile Ser Ser Lys Asp500 505 510Glu Glu Ser515<210>85<211>831<212>PRT<213>人(Homo sapiens)<400>85Asx Met Ala Val Gly Gly Gly His Lys Gly Val Arg Cys Pro Pro Ser1 5 10 15Ala Arg Ser Ser Gln Val Pro Thr Cys Cys Ala Gly Trp Arg Gln Gln20 25 30Gly Asp Glu Cys Gly Ile Ala Val Cys Glu Gly Asn Ser Thr Cys Ser35 40 45Glu Asn Glu Val Cys Val Arg Pro Gly Glu Cys Arg Cys Arg Hi s Gly50 55 60Tyr Phe Gly Ala Asn Cys Asp Thr Lys Cys Pro Arg Gln Phe Trp Gly65 70 75 80Pro Asp Cys Lys Glu Leu Cys Ser Cys His Pro His Gly Gln Cys Glu85 90 95Asp Val Thr Gly Gln Cys Thr Cys His Ala Arg Arg Trp Gly Ala Arg100 105 110Cys Glu His Ala Cys Gln Cys Gln His Gly Thr Cys His Pro Arg Ser115 120 125Gly Ala Cys Arg Cys Glu Ser Gly Trp Trp Gly Ala Gln Cys Ala Ser130 135 140Ala Cys Tyr Cys Ser Ala Thr Ser Arg Cys Asp Pro Gln Thr Gly Ala145 150 155 160Cys Leu Cys His Ala Gly Trp Trp Gly Arg Ser Cys Asn Asn Gln Cys165 170 175Ala Cys Asn Ser Ser Pro Cys Glu Gln Gln Ser Gly Arg Cys Gln Cys180 185 190Arg Glu Arg Thr Phe Gly Ala Arg Cys Asp Arg Tyr Cys Gln Cys Phe195 200 205Arg Gly Arg Cys His Pro Val Asp Gly Thr Cys Ala Cys Glu Pro Gly210 215 220Tyr Arg Gly Lys Tyr Cys Arg Glu Pro Cys Pro Ala Gly Phe Tyr Gly225 230 235 240Leu Gly Cys Arg Arg Arg Cys Gly Gln Cys Lys Gly Gln Gln Pro Cys245 250 255Thr Val Ala Glu Gly Arg Cys Leu Thr Cys Glu Pro Gly Trp Asn Gly260 265 270Thr Lys Cys Asp Gln Pro Cys Ala Thr Gly Phe Tyr Gly Glu Gly Cys275 280 285Ser His Arg Cys Pro Pro Cys Arg Asp Gly His Ala Cys Asn His Val290 295 300Thr Gly Lys Cys Thr Arg Cys Asn Ala Gly Trp Ile Gly Asp Arg Cys305 310 315 320Glu Thr Lys Cys Ser Asn Gly Thr Tyr Gly Glu Asp Cys Ala Phe Val325 330 335Cys Ala Asp Cys Gly Ser Gly His Cys Asp Phe Gln Ser Gly Arg Cys340 345 350Leu Cys Ser Pro Gly Val His Gly Pro His Cys Asn Val Thr Cys Pro355 360 365Pro Gly Leu His Gly Ala Asp Cys Ala Gln Ala Cys Ser Cys His Glu370 375 380Asp Thr Cys Asp Pro Val Thr Gly Ala Cys His Leu Glu Thr Asn Gln385 390 395 400Arg Lys Gly Val Met Gly Ala Gly Ala Leu Leu Val Leu Leu Val Cys405 410 415Leu Leu Leu Ser Leu Leu Gly Cys Cys Cys Ala Cys Arg Gly Lys Asp420 425 430Pro Thr Arg Arg Pro Arg Pro Arg Arg Glu Leu Ser Leu Gly Arg Lys435 440 445Lys Ala Pro His Arg Leu Cys Gly Arg Phe Ser Arg Ile Ser Met Lys450 455 460Leu Pro Arg Ile Pro Leu Arg Arg Gln Lys Leu Pro Lys Val Val Val465 470 475 480Ala His His Asp Leu Asp Asn Thr Leu Asn Cys Ser Phe Leu Glu Pro485 490 495Pro Ser Gly Leu Glu Gln Pro Ser Pro Ser Trp Ser Ser Arg Ala Ser500 505 510Phe Ser Ser Phe Asp Thr Thr Asp Glu Gly Pro Val Tyr Cys Val Pro515 520 525His Glu Glu Ala Pro Ala Glu Ser Arg Asp Pro Glu Val Pro Thr Val530 535 540Pro Ala Glu Ala Pro Ala Pro Ser Pro Val Pro Leu Thr Thr Pro Ala545 550 555 560Ser Ala Glu Glu Ala Ile Pro Leu Pro Ala Ser Ser Asp Ser Glu Arg565 570 575Ser Ala Ser Ser Val Glu Gly Pro Gly Gly Ala Leu Tyr Ala Arg Val580 585 590Ala Arg Arg Glu Ala Arg Pro Ala Arg Ala Arg Gly Glu Ile Gly Gly595 600 605Leu Ser Leu Ser Pro Ser Pro Glu Arg Arg Lys Pro Pro Pro Pro Asp610 615 620Pro Ala Thr Lys Pro Lys Val Ser Trp Ile His Gly Lys His Ser Ala625 630 635 640Ala Ala Ala Gly Arg Ala Pro Ser Pro Pro Pro Pro Gly Ser Glu Ala645 650 655Ala Pro Ser Pro Ser Lys Arg Lys Arg Thr Pro Ser Asp Lys Ser Ala660 665 670His Thr Val Glu His Gly Ser Pro Arg Thr Arg Asp Pro Thr Pro Arg675 680 685Pro Pro Gly Leu Pro Glu Glu Ala Thr Ala Leu Ala Ala Pro Ser Pro690 695 700Pro Arg Ala Arg Ala Arg Ala Ala Pro Arg Pro Leu Gly Ala His Gly705 710 715 720Arg Arg Arg Ser Pro Ala Lys Arg Ala Glu Ala Ala Ser Met Leu Ala725 730 735Ala Asp Val Arg Gly Lys Thr Arg Ser Leu Gly Arg Ala Glu Val Ala740 745 750Leu Gly Ala Gln Gly Pro Arg Glu Lys Pro Ala Pro Pro Gln Lys Ala755 760 765Lys Arg Ser Val Pro Pro Ala Ser Pro Ala Arg Ala Pro Pro Ala Thr770 775 780Glu Thr Pro Gly Pro Glu Lys Ala Ala Thr Asp Leu Pro Ala Pro Glu785 790 795 800Thr Pro Arg Lys Lys Thr Pro Ile Gln Lys Pro Pro Arg Lys Lys Ser805 810 815Arg Glu Ala Ala Gly Glu Leu Gly Arg Ala Gly Ala Pro Thr Leu820 825 830<210>86<211>871<212>PRT<213>人(Homo sapiens)<400>86Asx Met Glu Gly Ala Gly Pro Arg Gly Ala Gly Pro Ala Arg Arg Arg1 5 10 15Gly Ala Gly Gly Pro Pro Ser Pro Leu Leu Pro Ser Leu Leu Leu Leu20 25 30Leu Leu Leu Trp Met Leu Pro Asp Thr Val Ala Pro Gln Glu Leu Asn35 40 45Pro Arg Gly Arg Asn Val Cys Arg Ala Pro Gly Ser Gln Val Pro Thr50 55 60Cys Cys Ala Gly Trp Arg Gln Gln Gly Asp Glu Cys Gly Ile Ala Val65 70 75 80Cys Glu Gly Asn Ser Thr Cys Ser Glu Asn Glu Val Cys Val Arg Pro85 90 95Gly Glu Cys Arg Cys Arg His Gly Tyr Phe Gly Ala Asn Cys Asp Thr100 105 110Lys Cys Pro Arg Gln Phe Trp Gly Pro Asp Cys Lys Glu Leu Cys Ser115 120 125Cys His Pro His Gly Gln Cys Glu Asp Val Thr Gly Gln Cys Thr Cys130 135 140His Ala Arg Arg Trp Gly Ala Arg Cys Glu His Ala Cys Gln Cys Gln145 150 155 160His Gly Thr Cys His Pro Arg Ser Gly Ala Cys Arg Cys Glu Ser Gly165 170 175Trp Trp Gly Ala Gln Cys Ala Ser Ala Cys Tyr Cys Ser Ala Thr Ser180 185 190Arg Cys Asp Pro Gln Thr Gly Ala Cys Leu Cys His Ala Gly Trp Trp195 200 205Gly Arg Ser Cys Asn Asn Gln Cys Ala Cys Asn Ser Ser Pro Cys Glu210 215 220Gln Gln Ser Gly Arg Cys Gln Cys Arg Glu Arg Thr Phe Gly Ala Arg225 230 235 240Cys Asp Arg Tyr Cys Gln Cys Phe Arg Gly Arg Cys His Pro Val Asp245 250 255Gly Thr Cys Ala Cys Glu Pro Gly Tyr Arg Gly Lys Tyr Cys Arg Glu260 265 270Pro Cys Pro Ala Gly Phe Tyr Gly Leu Gly Cys Arg Arg Arg Cys Gly275 280 285Gln Cys Lys Gly Gln Gln Pro Cys Thr Val Ala Glu Gly Arg Cys Leu290 295 300Thr Cys Glu Pro Gly Trp Asn Gly Thr Lys Cys Asp Gln Pro Cys Ala305 310 315 320Thr Gly Phe Tyr Gly Glu Gly Cys Ser His Arg Cys Pro Pro Cys Arg325 330 335Asp Gly His Ala Cys Asn His Val Thr Gly Lys Cys Thr Arg Cys Asn340 345 350Ala Gly Trp Ile Gly Asp Arg Cys Glu Thr Lys Cys Ser Asn Gly Thr355 360 365Tyr Gly Glu Asp Cys Ala Phe Val Cys Ala Asp Cys Gly Ser Gly His370 375 380Cys Asp Phe Gln Ser Gly Arg Cys Leu Cys Ser Pro Gly Val His Gly385 390 395 400Pro His Cys Asn Val Thr Cys Pro Pro Gly Leu His Gly Ala Asp Cys405 410 415Ala Gln Ala Cys Ser Cys His Glu Asp Thr Cys Asp Pro Val Thr Gly420 425 430Ala Cys His Leu Glu Thr Asn Gln Arg Lys Gly Val Met Gly Ala Gly435 440 445Ala Leu Leu Val Leu Leu Val Cys Leu Leu Leu Ser Leu Leu Gly Cys450 455 460Cys Cys Ala Cys Arg Gly Lys Asp Pro Thr Arg Arg Pro Arg Pro Arg465 470 475 480Arg Glu Leu Ser Leu Gly Arg Lys Lys Ala Pro His Arg Leu Cys Gly485 490 495Arg Phe Ser Arg Ile Ser Met Lys Leu Pro Arg Ile Pro Leu Arg Arg500 505 510Gln Lys Leu Pro Lys Val Val Val Ala His His Asp Leu Asp Asn Thr515 520 525Leu Asn Cys Ser Phe Leu Glu Pro Pro Ser Gly Leu Glu Gln Pro Ser530 535 540Pro Ser Trp Ser Ser Arg Ala Ser Phe Ser Ser Phe Asp Thr Thr Asp545 550 555 560Glu Gly Pro Val Tyr Cys Val Pro His Glu Glu Ala Pro Ala Glu Ser565 570 575Arg Asp Pro Glu Val Pro Thr Val Pro Ala Glu Ala Pro Ala Pro Ser580 585 590Pro Val Pro Leu Thr Thr Pro Ala Ser Ala Glu Glu Ala Ile Pro Leu595 600 605Pro Ala Ser Ser Asp Ser Glu Arg Ser Ala Ser Ser Val Glu Gly Pro610 615 620Gly Gly Ala Leu Tyr Ala Arg Val Ala Arg Arg Glu Ala Arg Pro Ala625 630 635 640Arg Ala Arg Gly Glu Ile Gly Gly Leu Ser Leu Ser Pro Ser Pro Glu645 650 655Arg Arg Lys Pro Pro Pro Pro Asp Pro Ala Thr Lys Pro Lys Val Ser660 665 670Trp Ile His Gly Lys His Ser Ala Ala Ala Ala Gly Arg Ala Pro Ser675 680 685Pro Pro Pro Pro Gly Ser Glu Ala Ala Pro Ser Pro Ser Lys Arg Lys690 695 700Arg Thr Pro Ser Asp Lys Ser Ala His Thr Val Glu His Gly Ser Pro705 710 715 720Arg Thr Arg Asp Pro Thr Pro Arg Pro Pro Gly Leu Pro Glu Glu Ala725 730 735Thr Ala Leu Ala Ala Pro Ser Pro Pro Arg Ala Arg Ala Arg Ala Ala740 745 750Pro Arg Pro Leu Gly Ala His Gly Arg Arg Arg Ser Pro Ala Lys Arg755 760 765Ala Glu Ala Ala Ser Met Leu Ala Ala Asp Val Arg Gly Lys Thr Arg770 775 780Ser Leu Gly Arg Ala Glu Val Ala Leu Gly Ala Gln Gly Pro Arg Glu785 790 795 800Lys Pro Ala Pro Pro Gln Lys Ala Lys Arg Ser Val Pro Pro Ala Ser805 810 815Pro Ala Arg Ala Pro Pro Ala Thr Glu Thr Pro Gly Pro Glu Lys Ala820 825 830Ala Thr Asp Leu Pro Ala Pro Glu Thr Pro Arg Lys Lys Thr Pro Ile835 840 845Gln Lys Pro Pro Arg Lys Lys Ser Arg Glu Ala Ala Gly Glu Leu Gly850 855 860Arg Ala Gly Ala Pro Thr Leu865 870<210>87<211>134<212>PRT<213>人(Homo sapiens)<400>87Ile Asp Cys Arg Ala Glu Gln Gly Arg Thr Pro Leu Met Val Ala Val1 5 10 15Gly Leu Pro Asp Pro Ala Leu Arg Ala Arg Phe Val Arg Leu Leu Leu20 25 30Glu Gln Gly Ala Ala Val Asn Leu Arg Asp Glu Arg Gly Arg Thr Ala35 40 45Leu Ser Leu Ala Cys Glu Arg Gly His Leu Asp Ala Val Gln Leu Leu50 55 60Val Gln Phe Ser Gly Asp Pro Glu Ala Ala Asp Ser Ala Gly Asn Ser65 70 75 80Pro Val Met Trp Ala Ala Ala Cys Gly His Gly Ala Val Leu Glu Phe85 90 95Leu Val Arg Ser Phe Arg Arg Leu Gly Leu Arg Leu Asp Arg Thr Asn100 105 110Arg Ala Gly Leu Thr Ala Leu Gln Leu Ala Ala Ala Arg Gly His Gly115 120 125Thr Cys Val Gln Ala Leu130<210>88<211>324<212>PRT<213>人(Homo sapiens)<400>88Met Leu Lys Pro Lys Asp Leu Cys Pro Arg Ala Gly Thr Arg Thr Phe1 5 10 15Leu Glu Ala Met Gln Ala Gly Lys Val His Leu Ala Arg Phe Val Leu20 25 30Asp Ala Leu Asp Arg Ser Ile Ile Asp Cys Arg Ala Glu Gln Gly Arg35 40 45Thr Pro Leu Met Val Ala Val Gly Leu Pro Asp Pro Ala Leu Arg Ala50 55 60Arg Phe Val Arg Leu Leu Leu Glu Gln Gly Ala Ala Val Asn Leu Arg65 70 75 80Asp Glu Arg Gly Arg Thr Ala Leu Ser Leu Ala Cys Glu Arg Gly His85 90 95Leu Asp Ala Val Gln Leu Leu Val Gln Phe Ser Gly Asp Pro Glu Ala100 105 110Ala Asp Ser Ala Gly Asn Ser Pro Val Met Trp Ala Ala Ala Cys Gly115 120 125His Gly Ala Val Leu Glu Phe Leu Val Arg Ser Phe Arg Arg Leu Gly130 135 140Leu Arg Leu Asp Arg Thr Asn Arg Ala Gly Leu Thr Ala Leu Gln Leu145 150 155 160Ala Ala Ala Arg Gly His Gly Thr Ser Ala Gly Gly His Gly Gly Glu165 170 175Ala Gly Ser Ala Gly Lys Asn Ser Gly Arg His Arg Ala Gln Gly Ser180 185 190Glu Arg Pro Glu Leu Gly Arg Ser Met Ser Leu Ala Leu Gly Ala Val195 200 205Thr Glu Glu Glu Ala Ala Arg Leu Arg Ala Gly Ala Leu Met Ala Leu210 215 220Pro Asn Ser Pro Gln Ser Ser Gly Thr Gly Arg Trp Arg Ser Gln Glu225 230 235 240Val Leu Glu Gly Ala Pro Pro Thr Leu Ala Gln Ala Pro Ile Gly Leu245 250 255Ser Pro His Pro Glu Gly Gly Pro Gly Ser Gly Arg Leu Gly Leu Arg260 265 270Arg Arg Ser Thr Ala Pro Asp Ile Pro Ser Leu Val Gly Glu Ala Pro275 280 285Gly Pro Glu Ser Gly Pro Glu Leu Glu Ala Asn Ala Leu Ser Val Ser290 295 300Val Pro Gly Pro Asn Pro Trp Gln Ala Gly Thr Glu Ala Val Val Leu305 310 315 320Arg Ala Gln Arg
權(quán)利要求
1.一種分離的多肽，該多肽選自(a)一種分離的多肽，由包含表I所列的一種序列的多核苷酸編碼；(b)一種分離的多肽，包含表I所列的一種多肽序列；和(c)表I所列的一種基因的多肽序列。
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，其包含表I所列的一種多核苷酸序列；(b)表I所列的一種基因的分離的多核苷酸；(c)一種分離的多核苷酸，其包含編碼表I所列的一種多肽的多核苷酸序列；(d)一種分離的多核苷酸，編碼表I所列的一種多肽；(e)一種多核苷酸，該多核苷酸是(a)到(d)的多核苷酸的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，其包含多核苷酸，當(dāng)所述表達(dá)載體出現(xiàn)在相容性宿主細(xì)胞中時，該多核苷酸能夠產(chǎn)生權(quán)利要求1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產(chǎn)生權(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)胞在合適的培養(yǎng)條件下產(chǎn)生所述的多肽。
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。
6.一種膜，其為表達(dá)所述多肽的權(quán)利要求5所述重組宿主細(xì)胞的膜。
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，然后從所述培養(yǎng)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)明還公開了在診斷試驗中利用表I所列基因的多肽和多核苷酸的方法。
文檔編號A61K38/00GK1474869SQ01818830
公開日2004年2月11日 申請日期2001年9月13日 優(yōu)先權(quán)日2000年9月13日
發(fā)明者潘卡杰·阿加沃爾, 約翰·P·戈格斯韋爾, 賴英塔, 謝爾比·A·馬滕森, 蘭德爾·F·史密斯, 杰伊·C·斯特魯姆, 謝青, A 馬滕森, F 史密斯, C 斯特魯姆, P 戈格斯韋爾, 潘卡杰 阿加沃爾 申請人:史密絲克萊恩比徹姆公司, 史密絲克萊比奇曼公司, 葛蘭素集團(tuán)有限公司