專利名稱：：用于制備新的寡克隆抗體的方法用于制備新的寡克隆抗體的方法本發(fā)明涉及用于制備新的寡克隆抗體的方法，抗體自身以及其片段和其用途，以及抗原及配體。具體而言，本發(fā)明包含針對(duì)在冠狀動(dòng)脈斑塊中可能發(fā)現(xiàn)的抗原的抗體或其片段。本發(fā)明進(jìn)一步涉及用于免疫測(cè)定的、編碼這些抗體的核苷酸序列及這些抗體或其片段的氨基酸序列，還涉及這些抗體或其片段的配體。進(jìn)一步地，本發(fā)明包含涉及所述抗體或其片段或其配體的用途的診斷和治療應(yīng)用。
背景技術(shù)：
：急性冠狀動(dòng)脈綜合征(AcuteCoronarySyndrome，也簡(jiǎn)稱為ACS)為冠狀動(dòng)脈中斑塊破裂的表現(xiàn)。動(dòng)脈粥樣化斑塊的破裂或侵蝕伴隨動(dòng)脈的血栓和阻塞的形成可能引起心肌梗死禾口不穩(wěn)定型心絞痛(見"Newinsightsintoatheroscleroticplaquerupture"D.M.Braganza禾口M.R.Bennett,Postgrad.Med.J.2001；77；94-98作為一般參考)。動(dòng)脈粥樣化事件開始為形成非狹窄的脂肪條的脂質(zhì)滿載、單核細(xì)胞衍生的泡沫細(xì)胞和相關(guān)T細(xì)胞的內(nèi)皮下積累。病變(lesion)隨著發(fā)展采用了膽固醇酯的非細(xì)胞核心形式，以含有平滑肌細(xì)胞(VMSC)和炎性細(xì)胞(巨噬細(xì)胞和T淋巴細(xì)胞二者)的內(nèi)皮化纖維帽(fibrouscap)為界限。嚴(yán)重的病變中還存在新血管，并且鈣羥磷灰石的沉積物也可能出現(xiàn)于嚴(yán)重白勺病變中(JAL"Coronarydisease:Atherogenesiscurrentunderstandingofthecausesofatheroma，，PeterL.ffeissberg,Heart2000;83;247_252作為一般參考)。斑塊的細(xì)胞外脂質(zhì)核心由衍生自浸潤(rùn)動(dòng)脈壁的脂質(zhì)或衍生自死亡的泡沫細(xì)胞的游離膽固醇，膽固醇晶體以及膽固醇酯組成。脂質(zhì)核心可能通過(guò)引起對(duì)斑塊的肩部區(qū)域產(chǎn)生壓力而影響斑塊；例外，脂質(zhì)核心含有前血栓氧化脂質(zhì)且進(jìn)一步為衍生自巨噬細(xì)胞的組織因子所充滿，其中脂質(zhì)核心材料在暴露于循環(huán)血時(shí)是高度血栓形成性的(見，例如‘‘MechanismofPlaqueVulnerabilityandRupture，，PredimanK.Shah，JournaloftheAmericanCollegeofCardiology2003)0斑塊穩(wěn)定性還依賴于斑塊的血管平滑肌細(xì)胞(SMC)含量，因其能夠合成結(jié)構(gòu)上重要的I和III型膠原蛋白。相反，巨噬細(xì)胞和其他炎性細(xì)胞可釋放基質(zhì)金屬蛋白酶(MMP)，其降解膠原和細(xì)胞外基質(zhì)，從而有效地減弱斑塊(見，"Newinsightsintoatheroscleroticplaquerupture"D.M.Braganza禾口M.R.Bennett,Postgrad.Med.J.2001；77；94-98)。纖維帽的結(jié)構(gòu)組分包括基質(zhì)組分如衍生自SMC的膠原、彈性蛋白和蛋白聚糖。所述纖維帽防止斑塊的更深層組分與循環(huán)血接觸，并被觀察到在破裂的附近變薄(見，例如‘‘MechanismofPlaqueVulnerabilityandRupture，，PredimanK.Shah,JournaloftheAmericanCollegeofCardiology2003)0已經(jīng)顯示破裂的斑塊相對(duì)于完整的斑塊具有幾種組織形態(tài)學(xué)特征。因此，認(rèn)為當(dāng)其存在時(shí)，指示了對(duì)斑塊破裂的易感性(見，例如"MechanismofPlaqueVulnerabilityandRupture"PredimanK.Shah,JournaloftheAmericanCollegeofCardiology2003)。認(rèn)為斑塊形成所固有的可能原因之一是由對(duì)內(nèi)皮層的重復(fù)損傷所引起，所述損傷由四個(gè)“主要”危險(xiǎn)因素引起吸煙、高血壓、糖尿病和高脂血癥(高水平LDL和低水平HDL)。此外，損傷后內(nèi)皮紊亂在斑塊起始中起到至關(guān)重要的作用，因?yàn)橹|(zhì)可以更容易地從血流進(jìn)入到血管內(nèi)膜(tunicaintima)中。易感斑塊的破裂可自發(fā)發(fā)生，即沒(méi)有任何上文提到的誘因的發(fā)生或者在特定事件之后，如極度的體力活動(dòng)，嚴(yán)重的情感創(chuàng)傷和不同本質(zhì)或急性感染的壓力。斑塊破裂常常導(dǎo)致血栓形成，臨床表現(xiàn)為ACS。對(duì)斑塊破裂的血栓形成應(yīng)答很可能由斑塊上暴露的組成物的血栓形成性所調(diào)節(jié)；一般地，斑塊破裂發(fā)展于在具有壞死核心和被炎性細(xì)胞嚴(yán)重浸潤(rùn)的重疊薄纖維帽的病變中。由于血小板和壞死核心的物理接觸，腔血栓進(jìn)一步發(fā)展(見，例如，"Pathologicassessmentofthevulnerablehumancoronaryplaque”F.D.Kolodgie等人Heart2004；90；1385-1391)。纖維帽的破裂或侵蝕使高血栓生成性的膠原基質(zhì)和脂質(zhì)核心暴露于循環(huán)，不可避免地導(dǎo)致血小板積累和激活。這反過(guò)來(lái)導(dǎo)致纖維蛋白沉積以及血栓形成，其可能導(dǎo)致脈管阻塞，后者并非不可避免，如在沉默期的情況下(見，例如，“Coronarydisease:Atherogenesiscurrentunderstandingofthecausesofatheroma"PeterL.ffeissberg,Heart2000；83；247-252))。直到最近，動(dòng)脈粥樣化都被認(rèn)為是退化性的和慢性進(jìn)展的疾病，通過(guò)其對(duì)血流的機(jī)械性效應(yīng)引起癥狀，而現(xiàn)在理解這是能顯著變動(dòng)的動(dòng)態(tài)炎性過(guò)程。對(duì)動(dòng)脈粥樣化發(fā)生和進(jìn)展中的細(xì)胞和分子事件的近期研究集中注意于決定疾病結(jié)果的斑塊組分間的動(dòng)態(tài)相互作用上(JAL"Coronarydisease:Atherogenesis:currentunderstandingofthecausesofatheroma”PeterL.ffeissberg,Heart2000；83；247-252作為一般參考)。對(duì)于冠狀動(dòng)脈綜合征和幾種病原體之間的關(guān)系的數(shù)據(jù)存在著截然相反的數(shù)據(jù)，這些是需要評(píng)估的。在預(yù)期的研究中(見，例如"Impactofviralandbacterialinfectiousburdenonlongtermprognosisinpatientswithcoronaryarterydisease"RupprechtH.J.等人，Circulation2001，Jul3；104(1):25_31)，描述了一組1018個(gè)患者中中風(fēng)和8種不同病原體(單純皰疹病毒1-2，EB病毒(Epstein-Barr)，巨細(xì)胞病毒(Cytomegalovirus)，流感嗜血桿菌(Haemophilusinfluenzae),月市炎支原體(Mycoplasmapneumoniae)，幽門螺旋桿菌(Helicobacterpylori)和肺炎衣原體(Chlamydiapneumoniae))之間的關(guān)系；發(fā)現(xiàn)與六種到八種病原體陽(yáng)性血清相關(guān)的死亡率分別增加和12.6%。DePalma和他的小組("PatientswithAcuteCoronarySyndromeShowOligoclonalT-CellRecruitmentWithinUnstablePlaque"DePalma等人Circulation2006，113:640_646)對(duì)得自患急性冠狀動(dòng)脈綜合征的患者血液樣品以及直接來(lái)自其冠狀動(dòng)脈斑塊的T細(xì)胞進(jìn)行了其全部能力的研究?？贵w結(jié)構(gòu)存在五種類型的抗體(也叫做免疫球蛋白)IgG、IgA、IgD、IgM和IgE。在圖1中描繪了IgG的結(jié)構(gòu)，其包含兩條分子量大約為23KDa的輕鏈和兩條大約為53_70KDa的重鏈。這四條鏈通過(guò)二硫鍵彼此連接形成“Y”構(gòu)象。重鏈分類為y、n、a、S和￡，其中還有一些亞類，而輕鏈分類為K或入。每條重鏈包含一個(gè)恒定區(qū)和一個(gè)可變區(qū)，后者位于免疫球蛋白分子的N末端，長(zhǎng)度為大約100個(gè)氨基酸。具體而言，免疫球蛋白(Ig)重鏈和輕鏈的最可變部分為第三互補(bǔ)-決定區(qū)(⑶R3)，這是由V-D-J基因區(qū)段間的連接形成的一段短的氨基酸序列。⑶R3發(fā)現(xiàn)于與抗原互補(bǔ)的抗原受體(例如免疫球蛋白和T細(xì)胞受體)蛋白質(zhì)的可變結(jié)構(gòu)域。⑶R3部分的可變性是所生產(chǎn)的抗體數(shù)量升高的原因，這些抗體特異于任何抗原；所述可變性由在成熟B細(xì)胞產(chǎn)生過(guò)程中發(fā)生于骨髓中的V、D和J迷你基因的重排所決定。在此第一次重排發(fā)生后，當(dāng)成熟B細(xì)胞遇到抗原時(shí)，進(jìn)一步的超突變事件是抗體對(duì)于特定抗原的親和力增加的原因。經(jīng)常繪制“譜系樹”或“系統(tǒng)樹圖”以闡述免疫球蛋白通過(guò)可變區(qū)基因的體細(xì)胞超突變形成的多樣化。更具體地，過(guò)去已經(jīng)使用形象化發(fā)生中心B細(xì)胞突變的譜系關(guān)系的譜系樹生成，而證實(shí)發(fā)生中心作為體細(xì)胞超突變和親和力成熟的位置的作用。本發(fā)明包含的目的的實(shí)施例以下是本發(fā)明目的的示例性實(shí)施例，其通過(guò)全部公開內(nèi)容的教導(dǎo)可以更清楚。本發(fā)明的第一個(gè)目的包括編碼抗體重鏈且對(duì)應(yīng)于1-51、65_105、191-209、253-295、345-349、371-383和395-427中奇數(shù)號(hào)SequencelD的分離的多聚核苷酸序列。因此，本發(fā)明的第二個(gè)目的是編碼抗體重鏈且對(duì)應(yīng)于2-52，66-106、192-210、254-296,346-350,372-384和396-428中偶數(shù)號(hào)SequenceID的氨基酸序列。本發(fā)明的第三個(gè)目的是編碼抗體輕鏈且對(duì)應(yīng)于53-63、107-189、211_251、297-343、351-369、385-389和429-453中奇數(shù)號(hào)SequencelD的分離的多聚核苷酸分子。因此，本發(fā)明第四個(gè)目的是編碼抗體輕鏈且對(duì)應(yīng)于54-64，108-190、212-252、298-344,352-370,386-390和430-454中偶數(shù)號(hào)SequenceID的氨基酸序列。本發(fā)明的第五個(gè)目的包括表達(dá)載體，其包含編碼了對(duì)應(yīng)于2-390和396-454中偶數(shù)號(hào)SequenceID的氨基酸序列和其同源序列的一種或多種分離的多聚核苷酸分子，以及其互補(bǔ)序列。本發(fā)明另一個(gè)目的包括表達(dá)系統(tǒng)，其包含一種或多種本發(fā)明的分離的表達(dá)載體以及合適的宿主細(xì)胞。作為本發(fā)明進(jìn)一步的目的，提供了宿主細(xì)胞，包含一種或多種本發(fā)明的表達(dá)載體。本發(fā)明的另外一個(gè)目的包括生產(chǎn)重組抗體或其片段的方法，包括使用包含一種或多種分離的多聚核苷酸分子的本發(fā)明的表達(dá)系統(tǒng)，所述多聚核苷酸分子包含1-389和395-453中奇數(shù)號(hào)SequenceID以及其互補(bǔ)和同源序列。本發(fā)明進(jìn)一步的目的包括宿主細(xì)胞產(chǎn)生的分離的重組抗體或其片段，所述宿主細(xì)胞包含本發(fā)明的表達(dá)載體。本發(fā)明的另一個(gè)目的為包括使用一種或多種對(duì)應(yīng)于2-390和396-454中偶數(shù)號(hào)SequenceID的氨基酸序列和其同源序列的免疫測(cè)定。在本發(fā)明的另外一個(gè)實(shí)施方式中，提供了包含本發(fā)明的抗體或其任何片段以及連接在其上的治療部分的治療組合物。在本發(fā)明的進(jìn)一步的實(shí)施方式中，提供了包含連接在診斷部分上的本發(fā)明的抗體或其任何片段的診斷組合物。本發(fā)明更進(jìn)一步的實(shí)施方式是特異性結(jié)合于少一種本發(fā)明的抗體或其任何片段的配體。本發(fā)明進(jìn)一步的目的是用于篩選分子以鑒定對(duì)本發(fā)明的抗體或其任何片段具有最大結(jié)合親和力的分子的方法。作為本發(fā)明的另外一個(gè)實(shí)施方式是包括使用根據(jù)本發(fā)明鑒定的配體的免疫測(cè)定。在本發(fā)明的另外一個(gè)實(shí)施方式中，公開了治療或診斷組合物，其包含本發(fā)明的配體，所述配體共價(jià)連接至或者另外地在功能上結(jié)合于治療或診斷部分或?qū)嶓w。本發(fā)明的另一個(gè)實(shí)施方式是使用免疫抑制劑，免疫調(diào)諧劑或抗感染試劑用于制備治療冠狀動(dòng)脈疾病(如急性冠狀動(dòng)脈綜合征)或免疫相關(guān)病變的藥物組合物。在本發(fā)明進(jìn)一步的實(shí)施方式中，提供了用于鑒定引起免疫相關(guān)病變發(fā)展的病因?qū)W試劑的方法。本發(fā)明的另外一個(gè)實(shí)施方式是很可能在冠狀動(dòng)脈斑塊中發(fā)現(xiàn)的推定配體的氨基酸共有序列。在本發(fā)明的另外一個(gè)實(shí)施方式中，提供了顯示所述共有序列的4種肽。附圖簡(jiǎn)述圖1為IgG抗體分子和其Fab片段的結(jié)構(gòu)的示意表示。圖2表示用于抗體生產(chǎn)的重組形式。圖3表示人免疫球蛋白基因座的功能性基因區(qū)段的數(shù)量。圖4是制備根據(jù)本發(fā)明的抗體或其片段的示意表示。圖5顯示了對(duì)于冠狀動(dòng)脈斑塊樣品的重鏈的VDJ和VJ基因的分析。圖6a圖形顯示了與冠狀動(dòng)脈斑塊樣品相比，外周血樣品的輕鏈的同源性百分比。圖6b圖形顯示了與冠狀動(dòng)脈斑塊樣品相比，外周血樣品的重鏈的同源性百分比。圖7顯示了來(lái)自斑塊的重鏈的兩個(gè)克隆變體的核苷酸序列比對(duì)(#8e#24)。圖8顯示了來(lái)自斑塊的輕鏈的兩個(gè)克隆變體的氨基酸序列比對(duì)(#8e#15).圖9顯示了球蛋白(作為內(nèi)部對(duì)照)和標(biāo)準(zhǔn)球蛋白L48931的氨基酸序列的比對(duì)。圖10顯示了根據(jù)本發(fā)明使用的引物序列。A與K輕鏈可變區(qū)的5’退火的引物；B與K輕鏈恒定區(qū)的3’退火的引物；C與重鏈可變區(qū)的5’退火的引物；D與恒定區(qū)的3’退火的引物。圖11為譜系樹的示意表示。圖12為輕鏈的克隆相關(guān)組的突變譜系樹。圖13為重鏈的克隆相關(guān)組的突變譜系樹。圖14顯示了在H印-2細(xì)胞裂解物上的對(duì)Fab24的ELISA結(jié)果。圖15顯示了在合成配體上的對(duì)Fab24的ELISA結(jié)果。發(fā)明詳述定義在本發(fā)明中，除非另外有提供，術(shù)語(yǔ)“分離的多聚核苷酸”或“分離的核苷酸”指的是多聚核苷酸分子，其中多聚核苷酸的和核苷酸的與多聚核苷酸和核苷酸分別以相同意義可選地使用，其基本上沒(méi)有任何其他正常地在其天然發(fā)生環(huán)境中存在或與其相互作用的細(xì)胞物質(zhì)或組分，如其他核苷酸的或多聚核苷酸的序列的片段，蛋白質(zhì)或其它細(xì)胞組分。除非另外有提供，“互補(bǔ)序列，，指的是在嚴(yán)格條件下與目的序列雜交，產(chǎn)生分別在腺嘌呤和胸腺嘧啶殘基之間形成的兩個(gè)氫鍵，或胞嘧啶和鳥嘌呤殘基之間形成的三個(gè)氫鍵的序列，以及具有簡(jiǎn)并密碼子取代或沉默取代的其保守類似物，即，由于遺傳密碼的簡(jiǎn)并性對(duì)一個(gè)或兩個(gè)或三個(gè)連續(xù)核苷酸的取代產(chǎn)生了所編碼的相同氨基酸。在本發(fā)明的意義之內(nèi)的分離的多聚核苷酸，包括例如，基因或基因片段、外顯子、內(nèi)含子、mRNA、tRNA、rRNA、核酶、cDNA、質(zhì)粒、載體、分離的DNA、探針和引物。除非另外指出，除了上文所述特定的多聚核苷酸之外，本發(fā)明的分離的多聚核苷酸還包括其互補(bǔ)序列?！癱DNA”指的是連續(xù)編碼氨基酸序列的單鏈和雙鏈的互補(bǔ)DNA序列以及其任何同源序列和其任何片段，即其序列除去了內(nèi)含子，并可通過(guò)逆轉(zhuǎn)錄技術(shù)從分離的mRNA合成?！巴葱蛄小痹诒景l(fā)明的意義之內(nèi)指的是部分或幾乎與目的序列相同的任何序列；因此，這些單位為核苷酸或氨基酸時(shí)，兩個(gè)或多個(gè)序列的“同源性”或“一致性”來(lái)自對(duì)所述的核苷酸/氨基酸序列的總單位中占據(jù)相同位置的相同單位的數(shù)量的真實(shí)測(cè)量。例如，90%的同源性意味著在就最大匹配比對(duì)2個(gè)序列時(shí)，組成序列的每100個(gè)單位中有90個(gè)是相同的。在本發(fā)明之中，同源序列具有至少85%，優(yōu)選地90%、更優(yōu)選地95%，甚至更優(yōu)選至少99.5%的一致性。氨基酸的“保守取代”旨在表示為一種氨基酸被具有相同屬性的另一種氨基酸所取代，這樣，取代對(duì)肽的總體特征性屬性或功能沒(méi)有影響。這些保守取代的實(shí)例包括一種氨基酸用屬于如下相同組的另一種氨基酸所取代(i)具有帶電基團(tuán)的氨基酸，包括谷氨酸和天冬氨酸，賴氨酸，精氨酸和組氨酸；(ii)具有正電基團(tuán)的氨基酸，包括賴氨酸，精氨酸和組氨酸；(iii)具有負(fù)電基團(tuán)的氨基酸，包括谷氨酸和天冬氨酸；(iv)具有芳香基團(tuán)的氨基酸，包括苯丙氨酸，酪氨酸和色氨酸；(v)具有氮環(huán)基團(tuán)的氨基酸，包括組氨酸和色氨酸；(vi)具有大脂肪族非極性基團(tuán)的氨基酸，包括纈氨酸，亮氨酸和異亮氨酸；(vii)具有弱極性基團(tuán)的氨基酸，包含甲硫氨酸和半胱氨酸；(viii)具有小殘基基團(tuán)的氨基酸，包含絲氨酸，蘇氨酸，天冬氨酸，天冬酰胺，丙氨酸，谷氨酸，谷氨酰胺和脯氨酸；(ix)具有脂肪族基團(tuán)的氨基酸，包含纈氨酸，亮氨酸，異亮氨酸，甲硫氨酸和半胱氨酸；(x)具有小羥基基團(tuán)的氨基酸，包含絲氨酸和蘇氨酸。在下文的公開中、“CDR3”是一段短序列，指的是互補(bǔ)決定區(qū)，由編碼抗體的V-D-J基因(重鏈中)或V-J基因(輕鏈中)區(qū)段的連接形成。CDR3發(fā)現(xiàn)于與抗原互補(bǔ)的可變結(jié)構(gòu)域中?！皢蝹€(gè)克隆”指的是編碼抗體的CDR3區(qū)域的序列、其能夠特異性結(jié)合抗原/表位。顯示了相同⑶R3的序列被視為由相同克隆產(chǎn)生?！翱寺∽凅w”意指在與種系相比具有相同突變，相同VDJ或VJ基因用途以及相同D和J長(zhǎng)度的V區(qū)存在下，有一個(gè)或多個(gè)核苷酸或氨基酸的差異的任何序列?！爸脫Q突變”意指引起編碼其他氨基酸的核苷酸突變?！俺聊蛔儭币庵赣捎贒NA簡(jiǎn)并性而不引起所編碼的氨基酸變化的核苷酸突變?！氨磉_(dá)載體”意指任何用于轉(zhuǎn)運(yùn)遺傳信息的核苷酸分子?！胺蛛x的表達(dá)系統(tǒng)”意指用于氨基酸分子表達(dá)的系統(tǒng)，應(yīng)當(dāng)包括一種或多種包含編碼本發(fā)明的一種或多種氨基酸分子的核苷酸序列的表達(dá)載體以及將所述一種或多種載體轉(zhuǎn)染入的合適宿主細(xì)胞。本發(fā)明的“宿主細(xì)胞”意指包含一種或多種本發(fā)明的表達(dá)載體的細(xì)胞，其能夠產(chǎn)生對(duì)應(yīng)的所編碼的氨基酸序列或序列或其任何片段，通過(guò)例如將它們表達(dá)于其表面。根據(jù)本發(fā)明的“抗體”和“抗體片段”意指包括IgG、IgA、IgD、IgM或IgE中任何類型的全部抗體，也稱為免疫球蛋白以及其任何片段，如蛋白水解片段和/或重組片段，如Fab片段(在用木瓜蛋白酶消化Ig時(shí)產(chǎn)生)、F(ab’)2(在用胃蛋白酶消化免疫球蛋白時(shí)產(chǎn)生)、Fab’、Fv、單鏈抗體(scFv)和抗體的單鏈，例如重或輕單鏈。在本發(fā)明之內(nèi)的“配體”，意指結(jié)合本發(fā)明抗體的被識(shí)別的功能區(qū)域或其任何片段的任何試劑。根據(jù)本發(fā)明的“寡肽”為包含少于50個(gè)氨基酸殘基的氨基酸序列。在下文描述中，除非另外有提供，“種系”序列意指編碼抗體/免疫球蛋白或其無(wú)突變的任何片段的序列，因此，同源性百分比表示對(duì)突變事件的指示，任何類型的重鏈部分在與抗體接觸后會(huì)經(jīng)歷這些突變事件；更具體而言，所述的突變涉及抗體/免疫球蛋白或其任何片段的⑶R3部分。"RS突變”比率指的是在抗體/免疫球蛋白編碼序列的FR或⑶R3部分中發(fā)生的置換(R)和沉默(S)突變之間的比率。所述比率對(duì)于⑶R3高于對(duì)于FR序列，因?yàn)棰荝3為了適應(yīng)抗體的結(jié)構(gòu)經(jīng)歷了更高數(shù)量的突變事件。相反，F(xiàn)R—般為更保守的序列。p-值“P-值”表示了突變事件的顯著性。具體而言，重排的V區(qū)段的體細(xì)胞超突變過(guò)程以及對(duì)具有更高親和力的突變體的抗原選擇允許親和力的成熟，以產(chǎn)生具有對(duì)抗原改善的結(jié)合屬性的抗體。該過(guò)程導(dǎo)致直接參與抗原結(jié)合的CDR區(qū)域中置換突變(R)的積累。相反，沉默突變(S)在FR區(qū)域中積累，F(xiàn)R區(qū)域通常為更保守的序列以維持抗體的構(gòu)象。沒(méi)有抗體選擇時(shí)，隨機(jī)的突變過(guò)程導(dǎo)致R、S突變?cè)诳贵w重鏈和輕鏈序列上隨機(jī)分布。然而在選擇過(guò)程中，對(duì)于⑶R3的RS突變比率通常高于FR序列的比率。因此，通過(guò)由于偶然發(fā)生的突變的過(guò)量(對(duì)于CDR)或不足(對(duì)于FR)的多項(xiàng)分布模型而計(jì)算的P-值涉及抗原選擇過(guò)程的概率。低的P-值指示相比于對(duì)應(yīng)種系序列，重鏈和輕鏈的可變性的高概率是由于抗原_驅(qū)動(dòng)的抗體親和力成熟。顯著的p-值意指低于5%?！白V系樹”是研究B細(xì)胞分化途徑中體細(xì)胞超突變的有用手段，是通過(guò)對(duì)克隆相關(guān)細(xì)胞表達(dá)的抗體基因的分子分析進(jìn)行的。譜系樹通過(guò)圖表定義為有根的樹，其中節(jié)點(diǎn)對(duì)應(yīng)于B細(xì)胞受體基因序列(圖11)。對(duì)于兩個(gè)節(jié)點(diǎn)a和b，如果對(duì)應(yīng)于b的序列為對(duì)應(yīng)于a的序列的突變體，a與b至少差異為10一個(gè)突變并且比b離原始種系基因遠(yuǎn)至少一個(gè)突變，則稱b是a的子代。具有相同受體的兩個(gè)B細(xì)胞會(huì)對(duì)應(yīng)于相同的節(jié)點(diǎn)。樹上的節(jié)點(diǎn)可以是根節(jié)點(diǎn)，葉(終點(diǎn)序列)或內(nèi)部節(jié)點(diǎn)，其可以是分支節(jié)點(diǎn)(分枝點(diǎn))或通過(guò)節(jié)點(diǎn)。根意指表示了原始的B細(xì)胞。葉意指表示突變B細(xì)胞，其在取樣時(shí)是存活的并在觀察時(shí)無(wú)后代。內(nèi)部分支節(jié)點(diǎn)意指成熟過(guò)程中產(chǎn)生并具有超過(guò)一個(gè)后代的B細(xì)胞。內(nèi)部通過(guò)節(jié)點(diǎn)指的是恰恰具有一個(gè)子代的B細(xì)胞。樹干意指根到第一個(gè)分支節(jié)點(diǎn)的距離。根據(jù)第一個(gè)實(shí)施例，本發(fā)明涉及多聚核苷酸分子，其包含任何一條對(duì)應(yīng)于1-389和395-453中奇數(shù)號(hào)SequenceID的序列以及與其互補(bǔ)和同源的序列。本發(fā)明的多聚核苷酸序列編碼抗體或其任何片段的氨基酸序列，所述抗體或其任何片段結(jié)合很可能在冠狀動(dòng)脈斑塊中發(fā)現(xiàn)的抗原或其任何片段。優(yōu)選地，在本發(fā)明之內(nèi)，上文第一個(gè)實(shí)施方式中的分離的多聚核苷酸為cDNA分子。根據(jù)本領(lǐng)域熟知的步驟，通過(guò)逆轉(zhuǎn)錄從mRNA分子獲得cDNA。根據(jù)本發(fā)明的第一個(gè)目的，還提供對(duì)應(yīng)于2-390和396-454中偶數(shù)號(hào)SequenceID的氨基酸序列；以及其同源序列，和具有其保守替代和片段的任何序列。如所表示的，這些定義意指包括類似物序列，以包含那些序列，其在為氨基酸序列的情況下至少一個(gè)或多個(gè)氨基酸被衍生物如對(duì)應(yīng)的D-異構(gòu)物，或例如，對(duì)應(yīng)的硫酸化、糖基化或甲基化的氨基酸所取代；或者構(gòu)成序列的總氨基酸的一個(gè)或多個(gè)以及多至10%的氨基酸可被其衍生物所取代，例如半胱氨酸可被同型半胱氨酸所取代。還包括具有保守取代的序列。根據(jù)本發(fā)明，還包括編碼根據(jù)本發(fā)明第一個(gè)實(shí)施方式的抗體或其任何片段的多聚核苷酸序列，當(dāng)使用在ImMunoGeneTics中可得的數(shù)據(jù)庫(kù)(在網(wǎng)站http://imgt.cines.fr可得)時(shí)，所述多聚核苷酸序列具有與種系相比至少80%，優(yōu)選地至少90%，更優(yōu)選地至少95%，甚至更優(yōu)選地97%的同源性。另外，本發(fā)明第一個(gè)目的還包括超突變的氨基酸序列。因此，還包括編碼具有⑶R3部分的p-值小于5%，優(yōu)選地小于2%，更優(yōu)選地小于1%，甚至更優(yōu)選地小于1%。的氨基酸序列的多聚核苷酸序列以及其所編碼的氨基酸序列。如前文設(shè)定的，根據(jù)本發(fā)明，包括從分離自患者活性冠狀動(dòng)脈斑塊的合適樣品的mRNA上進(jìn)行的cDNA分子的合成。用于本發(fā)明的目的，所述的活性冠狀動(dòng)脈斑塊的合適樣品包括梗死發(fā)生事件后立即取樣的冠狀動(dòng)脈斑塊的樣品(即，所謂“新鮮樣品”)或者備選地，可取樣并將樣品在液氮中保存合適的一段時(shí)間以不損害或改變其組織學(xué)屬性并進(jìn)一步分析。對(duì)于本發(fā)明的目的，選擇了具有急性冠狀動(dòng)脈綜合征(ACS)的患者，這些患者已經(jīng)在入院48小時(shí)之內(nèi)經(jīng)歷了典型的胸痛，或暗示著心肌損傷的ECG變化。為了排除可能的混淆因素，排除具有近期的感染性疾病、免疫學(xué)障礙、免疫抑制性治療或腫瘤疾病的患者。根據(jù)熟知的方法從以上合適的樣品(即，從冠狀動(dòng)脈斑塊和外周血)中進(jìn)行mRNA分子的分離。作為一般參考，參見例如Molecularcloning.SambrookandRussell.Cold11SpringHarborLaboratoryPressColdSpringHarbor>NewYork.第三版2001。根據(jù)第二個(gè)實(shí)施方式，本發(fā)明的表達(dá)載體選自例如質(zhì)粒、粘粒、YAC、病毒顆?；蚴删w，且包含一種或多種根據(jù)本發(fā)明第一個(gè)實(shí)施方式的多聚核苷酸序列；在一個(gè)優(yōu)選的方面，表達(dá)載體為質(zhì)粒，包含一種或多種根據(jù)本發(fā)明第一個(gè)實(shí)施方式的多聚核苷酸序列。在本發(fā)明一個(gè)最優(yōu)選的實(shí)施方式中，表達(dá)載體(即，質(zhì)粒)包含一種或多種本發(fā)明的多聚核苷酸序列，其選自1-389和395-453中奇數(shù)號(hào)SequenceID。普通地，表達(dá)載體還包括復(fù)制的起點(diǎn)，可操作連接(S卩，以在引入細(xì)胞時(shí)允許核酸序列表達(dá)的方式連接于其上)的位于編碼序列上游的啟動(dòng)子，以及核糖體結(jié)合位點(diǎn)，RNA剪接位點(diǎn)，多聚腺苷酸化位點(diǎn)和轉(zhuǎn)錄序列。本領(lǐng)域技術(shù)人員將能夠構(gòu)建出適當(dāng)?shù)谋磉_(dá)載體，以及因此根據(jù)所選擇的宿主細(xì)胞的任何適當(dāng)?shù)谋磉_(dá)載體；例如，通過(guò)選擇宿主生物體所識(shí)別的啟動(dòng)子。在甚至更優(yōu)選的實(shí)施方式中，本發(fā)明的表達(dá)載體為Burioni等人(HumanAntibodies2001；10(3-4)149-54)描述的載體。根據(jù)本發(fā)明第三個(gè)實(shí)施方式的分離的表達(dá)系統(tǒng)可包含一個(gè)單個(gè)表達(dá)載體，其包含一種或多種本發(fā)明的任何多聚核苷酸序列。備選地，上述表達(dá)系統(tǒng)可包含兩種或多種表達(dá)載體，其中每種包含一種或多種本發(fā)明的任何多聚核苷酸分子。例如，表達(dá)載體可包含編碼抗體的輕鏈或其片段的本發(fā)明的多聚核苷酸分子，并且第二表達(dá)載體包括編碼抗體的重鏈或其片段的本發(fā)明的聚核苷酸分子。在本發(fā)明的一個(gè)實(shí)施方式中，表達(dá)系統(tǒng)包含單個(gè)表達(dá)載體，其包括包含1-389和395-453中奇數(shù)號(hào)SequenceID,并且編碼這些氨基酸序列且對(duì)應(yīng)于2_390和396-454中偶數(shù)號(hào)SequenceID及其任何同源序列的一種或多種多聚核苷酸分子。在本發(fā)明的一個(gè)優(yōu)選的實(shí)施方式中，表達(dá)系統(tǒng)包含一種表達(dá)載體，其包含編碼輕鏈的多聚核苷酸序列，即，選自對(duì)應(yīng)于53-63、107-189、211-251、297-343、351-369、385-389和429-453中奇數(shù)號(hào)SequencelD的序列，以及編碼重鏈的第二多聚核苷酸序列，S卩，選自對(duì)應(yīng)于1-51、65-105、191-209、253-295、345-349、371-383和395-427中奇數(shù)號(hào)SequenceID的序列。在本發(fā)明一個(gè)最優(yōu)選的實(shí)施方式中，表達(dá)系統(tǒng)包括包含編碼SequenceIDn°53所示的輕鏈的多聚核苷酸序列的載體，以及第二載體，其包含編碼分別在SequenceIDn°21、37、43和51中所示的重鏈的多聚核苷酸序列中的任意一種。組成本發(fā)明的表達(dá)系統(tǒng)的表達(dá)載體的制備包括根據(jù)本領(lǐng)域熟知的方法將適當(dāng)?shù)暮怂岱肿硬迦胍环N或多種載體，其一般包含一種或多種信號(hào)序列、復(fù)制起點(diǎn)、一種或多種標(biāo)志物基因序列、增強(qiáng)子元件、啟動(dòng)子以及轉(zhuǎn)錄終止序列。所述步驟的一般參考見，例如Phagedisplay、ColdSpringHarborLaboratoryPress.ColdSpringHarbor、紐約。例如，編碼本發(fā)明重鏈的序列與Flag或六組氨酸尾巴一起插入表達(dá)載體中，可易于檢測(cè)。根據(jù)本發(fā)明的先前實(shí)施方式的宿主細(xì)胞可以為例如原核細(xì)胞或真核細(xì)胞。合適的原核細(xì)胞包括革蘭氏陰性的和革蘭氏陽(yáng)性的，包括例如腸桿菌科如埃希氏12菌屬(Escherichia)(例如大腸桿菌(E.coli))，腸桿菌屬(Enterobacter)，歐文式菌屬(Erwinia)，克雷伯菌屬(Klebsiella)，變形桿菌屬(Proteus)，沙門氏菌屬(Salmonella)(例如鼠傷寒沙門氏菌(Salmonellatyphimurium))，沙雷氏菌屬(Serratia)(例如粘質(zhì)沙雷氏菌(Serratiamarcescans))和志賀氏菌屬(Shigella)以及桿菌屬(Bacilli)(如枯草芽孢桿菌(B.subtilis)和地衣芽孢桿菌(B.licheniformis))，假單胞菌屬(Pseudomonas)(如銅綠假單胞菌(P.aeruginosa))和鏈霉菌屬(Str印tomyces)。例如，可使用的公開可得的菌株為例如，大腸桿菌K12株MM294(ATCC31，446)；大腸桿菌X1776(ATCC31，537)；大腸桿菌株W3110(ATCC27,325)和K5772(ATCC53,635)或大腸桿菌XLl-Blue，表示了優(yōu)選的大腸桿菌株。除了原核細(xì)胞之外，真核微生物如絲狀真菌或酵母為合適的宿主細(xì)胞。通常使用的是釀酒酵母(Saccharomycescerevisiae)，也被稱為普通面包酵母；其他酵母為例如酵母屬(Saccharomyces)、巴斯德畢赤酵母(Pichiapastoris)，或克魯維酵母屬(Kluyveromyces)(如乳酸克魯維酵母(K.lactis)、脆壁克魯維酵母(K.fragilis)，保加利亞克魯維酵母(K.bulgaricuS)、魏氏克魯維酵母(K.wickeramii)、瓦爾特克魯維酵母(K.waltii)，果蠅克魯維酵母(K.drosophilarum)、耐熱克魯維酵母(K.thermotolerans)及馬克斯克魯維酵母(K.marxianus))，裂殖酵母屬(Schizosaccharomyces)(如粟酒裂殖酵母(Schizosaccharomycespombe)、子囊酵母屬(yarrowia)，漢森酵母屬(Hansenula),里氏木霉(Trichodermareesia),粗糖鏈抱霉(Neurosporacrassa)、許旺酵母屬(Schwanniomyces)(如西方許旺酵母(Schwanniomycesoccidentalis)、鏈孢霉屬(Neurospora)，青霉屬(Penicillium)，彎頸霉(Tolypociadium),曲霉屬(Aspergillus)(如構(gòu)巢曲霉(A.nidulans))，假絲酵母屬(Candida)，球擬酵母屬(Torulopsis)和紅酵母屬(Rhodotorula)。此外，用于制備表達(dá)系統(tǒng)的合適的真核細(xì)胞也可衍生自多細(xì)胞生物體，如來(lái)自無(wú)脊椎動(dòng)物細(xì)胞或植物細(xì)胞。植物細(xì)胞包括，例如根癌農(nóng)桿菌(Agrobacteriumtumeffaciens)和煙草(Nicotianatabacum)。此外，可使用昆蟲細(xì)胞，包括例如果蠅(Drosophila)S2和夜蛾(Spodoptera)Sf90反過(guò)來(lái)，哺乳類宿主細(xì)胞包括中國(guó)倉(cāng)鼠卵巢(CH0)和COS細(xì)胞。更特異性的實(shí)例進(jìn)一步包括由SV40轉(zhuǎn)化的猴腎CVI細(xì)胞系(C0S-7，ATCCCRL1651)；人胚腎細(xì)胞系，中國(guó)倉(cāng)鼠卵巢細(xì)胞/-DHFR，小鼠支持細(xì)胞，人肺細(xì)胞(W138，ATCCCCL75)；人肝細(xì)胞(HepG2，HB8065)；和小鼠乳腺腫瘤(MMT060562，ATCCCCL51)。對(duì)適當(dāng)?shù)乃拗骷?xì)胞的選擇被認(rèn)為是本領(lǐng)域技術(shù)人員已知的知識(shí)，S卩，原核細(xì)胞可用于制備抗體片段如Fab、而對(duì)于制備完整抗體如IgG時(shí)可使用真核細(xì)胞如酵母。用于細(xì)胞轉(zhuǎn)染和轉(zhuǎn)化以制備包含以上表達(dá)載體的上文公開的宿主細(xì)胞的方法依賴于所用的宿主細(xì)胞，且是本領(lǐng)域普通技術(shù)人員已知的。例如，用鈣或電穿孔的處理一般用于原核細(xì)胞，而用根癌農(nóng)桿菌的感染用于轉(zhuǎn)化特定植物細(xì)胞。對(duì)于哺乳類細(xì)胞，可使用如Graham和vanderEb,Virology,52456-457(1978)公開的磷酸鈣沉淀。然而，也可使用用于將多聚核苷酸序列引入細(xì)胞內(nèi)的其他方法例如核顯微注射、電穿孔、細(xì)菌與完整細(xì)胞的融合或多聚陽(yáng)離子。13此外，宿主細(xì)胞還可移植到動(dòng)物中以生產(chǎn)轉(zhuǎn)基因非-人動(dòng)物，用于制備人化抗體或其片段。優(yōu)選的非-人動(dòng)物包括例如小鼠、大鼠、兔、倉(cāng)鼠。根據(jù)本領(lǐng)域已知方法生產(chǎn)本發(fā)明第五個(gè)實(shí)施方式的重組抗體和其片段，包括使用本發(fā)明的分離的多聚核苷酸序列。具體而言，所述的方法包括以下步驟a)從合適的冠狀動(dòng)脈斑塊樣品中分離mRNA；b)進(jìn)行逆轉(zhuǎn)錄以獲得對(duì)應(yīng)的cDNA；c)制備包含從步驟b)中獲得的一種或多種cDNA分子以及任意一種上文公開的合適的宿主細(xì)胞的表達(dá)系統(tǒng)；d)在合適的生長(zhǎng)條件下培養(yǎng)宿主細(xì)胞；e)回收生產(chǎn)的抗體或其任何片段；以及f)純化所述抗體或其任何片段。具體而言，步驟a)-f)根據(jù)本領(lǐng)域已知方法進(jìn)行，從以下實(shí)施例會(huì)變得清楚。為評(píng)估對(duì)由統(tǒng)計(jì)上發(fā)生的突變或其它不同于冠狀動(dòng)脈斑塊的B細(xì)胞成熟中涉及的機(jī)制獲得的結(jié)果的影響，還在具有保守區(qū)域的一小部分基因上進(jìn)行克隆和測(cè)序。這樣，選擇球蛋白基因作為內(nèi)部參考；具體而言，使用標(biāo)準(zhǔn)球蛋白L48931。因此，本發(fā)明進(jìn)一步的目的是，本發(fā)明的宿主細(xì)胞生產(chǎn)的以及根據(jù)上文公開的方法產(chǎn)生的分離的重組抗體和其片段，包括IgG型免疫球蛋白(簡(jiǎn)稱為Ig)，而“其片段”優(yōu)選地包括IgG的Fab片段。優(yōu)選地，本發(fā)明的IgG的分離的重組抗體片段包含SequenceIDn°54中闡述的氨基酸序列，備選地，包含SequenceIDn°22、44、52和38中所示的任何一段氨基酸序列。根據(jù)本發(fā)明，還包括編碼可根據(jù)以上公開的過(guò)程生產(chǎn)的抗體或其任何片段的氨基酸序列，當(dāng)使用ImMunoGeneTics中可得的數(shù)據(jù)庫(kù)(通過(guò)網(wǎng)站http//imgt.cines.fr可得)時(shí)具有與種系相比至少80%，優(yōu)選地至少90%，更優(yōu)選地至少95%甚至更優(yōu)選地至少97%的同源性。此外，還包括氨基酸序列，其⑶R3部分p值小于5%，優(yōu)選地小于2%，更優(yōu)選地小于1%，甚至更優(yōu)選地小于1%。。根據(jù)本發(fā)明的另一個(gè)目的，提供了免疫測(cè)定，其包含使用根據(jù)本發(fā)明生產(chǎn)的抗體或其任何片段。免疫測(cè)定是基于抗原/抗體復(fù)合體形成的測(cè)試，可以是競(jìng)爭(zhēng)性或非競(jìng)爭(zhēng)性的。競(jìng)爭(zhēng)性免疫測(cè)定包括測(cè)試含有特定抗原的未知樣品，該抗原與另一標(biāo)記的抗原競(jìng)爭(zhēng)與抗體的結(jié)合；因此，反應(yīng)與未知樣品中抗原的濃度成反比。相反地，非競(jìng)爭(zhēng)性免疫測(cè)定(也叫做“三明治測(cè)定”)包括使用固定化的抗體，其被抗原結(jié)合，因此形成被標(biāo)記的抗體靶向的復(fù)合體；因此所述的方法的結(jié)果直接與抗原濃度成比例。廣泛使用的免疫測(cè)定包括例如，RIA(放射免疫測(cè)定(RadiolmmunoAssay))、Western印跡、ELISA(酶聯(lián)免疫吸附測(cè)定)、免疫染色、免疫沉淀、免疫電泳、免疫熒光、發(fā)光免疫測(cè)定(luminescentimmunoassay，LIA)、免疫組化，都是實(shí)驗(yàn)室實(shí)踐中常規(guī)使用的。根據(jù)本發(fā)明的優(yōu)選的免疫測(cè)定為ELISA測(cè)試。ELISA是已經(jīng)廣為接受的生化技術(shù)，其使得能夠?qū)o定樣品中的生物分子如抗體或其片段、抗原、蛋白質(zhì)、激素和其他有機(jī)分子進(jìn)行檢測(cè)和進(jìn)一步的定量；優(yōu)選地，根據(jù)本發(fā)明，上文提到的ELISA測(cè)試用于檢測(cè)特定的抗原。具體而言，ELISA測(cè)試可包括使用兩種抗體，其中一種——第一抗體——對(duì)目的分子(即抗原)有選擇性，將其固定化在ELISA板上。加入可能含有所述目的分子的混合物，允許孵育合適且足夠的時(shí)間，然后進(jìn)行第一步洗滌以移除未結(jié)合的物質(zhì)。進(jìn)一步加入偶聯(lián)于酶上并特異于目的分子和第一抗體之間形成的復(fù)合體的第二抗體。之后進(jìn)行ELISA板的第二步洗滌并加入顯色底物。所得的顏色變化可通過(guò)分光光度計(jì)技術(shù)評(píng)估，通過(guò)標(biāo)準(zhǔn)比色曲線直接與所形成的復(fù)合體的量相關(guān)，并因此與樣品中存在的目的分子濃度相關(guān)。待通過(guò)本發(fā)明的上述免疫測(cè)定進(jìn)行測(cè)試的樣品為例如梗死事件后立即取自患者的不穩(wěn)定冠狀動(dòng)脈斑塊，即，如前文所述的所謂“新鮮”樣品或在取樣后保存于液氮中的樣品；備選地，其可由全血或血清樣品構(gòu)成。當(dāng)包括在用于篩選有或沒(méi)有發(fā)展急性冠狀動(dòng)脈綜合征(ACS)或其它冠狀動(dòng)脈疾病的風(fēng)險(xiǎn)的人群的程序中時(shí)，根據(jù)本發(fā)明的免疫測(cè)定測(cè)試為有價(jià)值的診斷工具。作為本發(fā)明另外一個(gè)實(shí)施方式，公開了一種治療組合物，其包含本發(fā)明的抗體或其任何片段以及與其共價(jià)連接的治療部分。所述的治療組合物能夠選擇性地將治療試劑靶向至冠狀動(dòng)脈斑塊位點(diǎn)。所述被靶向的組合物的熟知優(yōu)勢(shì)包括減少要施用的有效成分的量，因此減少了其潛在的副作用等等。對(duì)于所述的目的，治療部分可包括非限制性實(shí)例放射性核素、藥物、激素、激素拮抗物、受體拮抗物、酶或被另一種試劑激活的酶原、自分泌因子或細(xì)胞因子、抗微生物試劑；也可使用毒素。還包括藥物和前藥。本發(fā)明的進(jìn)一步實(shí)施方式涉及包含與用于顯示冠狀動(dòng)脈斑塊位點(diǎn)的診斷性部分相連的本發(fā)明的抗體或其任何片段的診斷組合物。根據(jù)本發(fā)明的診斷組合物包含根據(jù)本發(fā)明生產(chǎn)的抗體或其任何片段，其共價(jià)連接至少一種診斷部分以選擇性靶向至冠狀動(dòng)脈斑塊位點(diǎn)，這樣定位了斑塊位點(diǎn)。因此，有可能精確地定位冠狀動(dòng)脈斑塊發(fā)展位點(diǎn)，甚至更好地理解發(fā)生的病變的發(fā)展程度。此外，這代表了在通過(guò)外科手術(shù)移除斑塊之前非常有用的工具。診斷部分使得能夠通過(guò)在醫(yī)藥領(lǐng)域使用的可視化技術(shù)進(jìn)行檢測(cè)，例如MRI(磁共振成像)、CT(計(jì)算機(jī)斷層攝影)、超聲，描述生態(tài)學(xué)，X-射線和本領(lǐng)域技術(shù)人員知識(shí)范圍內(nèi)的其他診斷技術(shù)。根據(jù)要使用的診斷技術(shù)選擇診斷部分的種類。根據(jù)本發(fā)明更進(jìn)一步的目的，提供了配體，也就是確實(shí)選擇性地結(jié)合抗體或其任何片段的分子。本發(fā)明的配體也可以為結(jié)合靶抗體或其片段的任何表面或內(nèi)部序列或構(gòu)象結(jié)構(gòu)域或任何其他部分的試劑。因此本發(fā)明的“配體”包括除了其結(jié)合目的靶標(biāo)沒(méi)有明顯生物學(xué)功能的試劑。這樣，蛋白質(zhì)，肽，多糖，糖蛋白，激素，受體，細(xì)胞表面抗原，抗體或其片段如Fab片段、F(ab')2、Fab’、Fv和單鏈抗體(scFv)或甚至抗獨(dú)特型抗體，毒素，病毒，底物，代謝物，過(guò)渡態(tài)類似物，協(xié)同因子，抑制子，藥物，染料，營(yíng)養(yǎng)物，生長(zhǎng)因子等等也非限制地包括在上文定義中。在一個(gè)優(yōu)選的實(shí)施方式中，本發(fā)明的配體為如上文定義的寡肽；優(yōu)選地為包含4-12個(gè)氨基酸的肽，更優(yōu)選地為包含4-10個(gè)氨基酸的肽，甚至更優(yōu)選地為包含6-8個(gè)氨基酸的肽。可通過(guò)對(duì)化合物文庫(kù)進(jìn)行篩選測(cè)試而對(duì)這些配體進(jìn)行鑒定。具體而言，根據(jù)本發(fā)明，所述的鑒定包括使用本發(fā)明提供的抗體或其任何片段。因此用于鑒定本公開抗體或其任何片段的配體的方法代表了本發(fā)明一個(gè)進(jìn)一步的目的。例如，所述的方法可能包括將抗體或其片段例如通過(guò)鏈霉親和素_生物素連接結(jié)合到固相上，隨后將待測(cè)分子與這樣制備的固相接觸以使其結(jié)合于互補(bǔ)抗體，然后洗滌以移除未結(jié)合的物質(zhì)；最后，結(jié)合程度能通過(guò)多種方法如ELISA測(cè)試進(jìn)行確定。優(yōu)選地，所述ELISA測(cè)試是這樣的測(cè)試，其中選自本發(fā)明的抗體中的第一抗體或其片段通過(guò)例如生物素/鏈霉親和素連接而連接于固相，然后加入含有待測(cè)分子的混合物，進(jìn)行一段合適的時(shí)間的孵育，隨后洗滌以移除未結(jié)合的物質(zhì)。之后，混入第二抗體并再次進(jìn)行孵育。這樣顯示對(duì)于本發(fā)明的抗體或其片段最高親和力的分子可進(jìn)行分離，鑒定以及根據(jù)熟知的方法進(jìn)行定量(如通過(guò)比色測(cè)量)。備選地，本發(fā)明的另外一個(gè)實(shí)施方式提供了免疫測(cè)定，其包括使用根據(jù)本發(fā)明鑒定的配體。對(duì)于本發(fā)明第二個(gè)目的，所述的免疫測(cè)定可以為上文已經(jīng)提到的免疫測(cè)定中任意一種。例如，用于所要求保護(hù)的發(fā)明的免疫酶測(cè)試可以為如實(shí)施例10中進(jìn)一步詳述的免疫組織學(xué)測(cè)定。能進(jìn)行上述免疫組織學(xué)測(cè)定以調(diào)查根據(jù)上述實(shí)施方式在本發(fā)明中鑒定和公開的配體在斑塊內(nèi)的存在情況。在本發(fā)明的另外一個(gè)實(shí)施方式中公開了治療組合物，其包含通過(guò)本發(fā)明上述方法鑒定的且共價(jià)連接于治療部分的配體。用于所述目的的治療部分可以為任意一種已經(jīng)在上文描述的部分。具體而言，這樣提供的治療組合物可選擇性地將治療試劑靶向至冠狀動(dòng)脈斑塊位點(diǎn)o還公開了診斷組合物，其包含通過(guò)本發(fā)明上述方法鑒定的且共價(jià)連接于診斷部分的配體。用于所述目的的診斷部分可以為任意一種已經(jīng)在上文描述的部分。用于本發(fā)明的另外一個(gè)實(shí)施方式要求保護(hù)免疫抑制化合物在制備用于治療冠狀動(dòng)脈疾病如急性冠狀動(dòng)脈綜合征(ACS)或免疫相關(guān)病變的藥物化合物中的用途。免疫相關(guān)病變包括以下病變，其中引發(fā)和控制免疫反應(yīng)的生理機(jī)制被改變了。免疫抑制化合物通過(guò)非限制性實(shí)例可選自糖皮質(zhì)激素，烷基化試劑，抗代謝物，氨甲蝶呤，硫唑嘌呤和巰基嘌呤，細(xì)胞毒性抗生素如更生霉素，蒽環(huán)霉素，絲裂霉素C，博萊霉16素、光輝霉素、環(huán)孢素、干擾素、類阿片、TNF結(jié)合蛋白質(zhì)、霉酚酸酯(mycophenolate)、小生物學(xué)試劑的一組；此外，還包含單克隆和多克隆抗體。在進(jìn)一步的實(shí)施方式中，本發(fā)明提供了用于鑒定、顯示和定性局部抗原特異性的和抗原驅(qū)動(dòng)的對(duì)免疫系統(tǒng)刺激的方法，提供了能用于鑒定病因?qū)W，用于確定靶標(biāo)和用于設(shè)計(jì)免疫治療和免疫預(yù)防的有用的細(xì)節(jié)。具體而言，所述方法包括測(cè)試本發(fā)明的抗體或其任何片段對(duì)于潛在地引起冠狀動(dòng)脈疾病發(fā)展作用的病原試劑的親和力的步驟。為了更好地理解本發(fā)明，非限制性地給出以下實(shí)施例。實(shí)施例1樣品采集la)冠狀動(dòng)脈粥樣化斑塊的取樣從經(jīng)歷冠狀動(dòng)脈切除術(shù)的急性冠狀動(dòng)脈綜合征患者的粥樣化斑塊獲得足夠量的組織，并將其儲(chǔ)存于液氮。lb)外周血的取樣同時(shí)取5ml來(lái)自相同患者(從其取得實(shí)施例la的組織)的外周血并儲(chǔ)存于用EDTA處理的管中。實(shí)施例2:mRNA提取2a)從冠狀動(dòng)脈斑塊中提取mRNA將根據(jù)實(shí)施例la取得的斑塊進(jìn)行勻漿，并根據(jù)常規(guī)方法學(xué)根據(jù)制造商提供的說(shuō)明書使用用于提取mRNA的商業(yè)試劑盒(Rneasy試劑盒、Qiagen、德國(guó))提取總mRNA。2b)從外周血樣品中提取mRNA在37°C下，將根據(jù)實(shí)施例lb采集的5ml外周血稀釋于等體積的PBS(磷酸緩沖鹽溶液)中，覆蓋于15ml的HistOpaque-1077(Sigma-AldriCh，圣路易斯，密蘇里)上，室溫下以300g離心30分鐘。在界面處使用巴斯德吸頭采集淋巴細(xì)胞，稀釋于15mlPBS中并以300g進(jìn)一步離心。將所得的沉淀重懸于15ml的PBS中，取出小的等分試樣以使用計(jì)數(shù)室(Burker)計(jì)數(shù)細(xì)胞。最后，將細(xì)胞懸液以300g離心，根據(jù)上文描述的步驟對(duì)所得的沉淀進(jìn)行mRNA提取。實(shí)施例3:mRNA逆轉(zhuǎn)錄3a)來(lái)自冠狀動(dòng)脈斑塊樣品的mRNA的逆轉(zhuǎn)錄根據(jù)制造商的說(shuō)明書，使用用于mRNA逆轉(zhuǎn)錄的商業(yè)試劑盒SuperscriptIIIRT(Sigma-Aldrich,圣路易斯，密蘇里)對(duì)來(lái)自實(shí)施例2a的冠狀動(dòng)脈斑塊樣品的mRNA進(jìn)行逆轉(zhuǎn)錄。根據(jù)標(biāo)準(zhǔn)步驟以寡聚(dT)為引物由總mRNA進(jìn)行cDNA合成。3b)來(lái)自外周血樣品的mRNA的逆轉(zhuǎn)錄對(duì)根據(jù)實(shí)施例2b獲得的mRNA進(jìn)行與實(shí)施例3a相同的步驟。實(shí)施例4cDNA序列的擴(kuò)增4a)來(lái)自冠狀動(dòng)脈斑塊樣品的cDNA序列的擴(kuò)增以lyl獲自實(shí)施例3a的cDNA進(jìn)行多聚酶鏈?zhǔn)椒磻?yīng)。設(shè)計(jì)反向引物以分別與編碼重鏈和輕鏈恒定區(qū)序列區(qū)段相退火(圖10B和D分別表示輕鏈和重鏈)。正向引物為“家族特異性的”，并設(shè)計(jì)為對(duì)應(yīng)于第一框架區(qū)中重鏈和輕鏈基因的5’末端(圖10A和C分別為輕鏈禾口重鏈)；JALPhagedisplay、ColdSpringHarborLaboratoryPress.ColdSpring17Harbor，紐約，第三版2001作為參考。對(duì)于重鏈，使用了特異于IgGl和IgG2同種型的引物，而對(duì)于輕鏈?zhǔn)褂昧颂禺愑贙同種型的引物。擴(kuò)增輪次以以下熱特性進(jìn)行94°C15秒、52°C1分鐘，72°C90秒。反應(yīng)進(jìn)行35個(gè)循環(huán)。每個(gè)反應(yīng)中包括陰性對(duì)照(相同混合物，不含DNA)和陽(yáng)性對(duì)照(插入了已知序列)。PCR產(chǎn)物在含溴化乙錠的2%瓊脂糖膠中進(jìn)行電泳分析。反應(yīng)產(chǎn)生了對(duì)應(yīng)輕鏈的三650bp條帶以及對(duì)應(yīng)重鏈的700bp條帶。根據(jù)制造商的說(shuō)明書使用用于DNA提取的商業(yè)試劑盒(QIAquickgelextractionkit;Qiagen，德國(guó))從膠中提取擴(kuò)增子(即PCR過(guò)程的產(chǎn)物)。最后通過(guò)標(biāo)準(zhǔn)方法回收PCR產(chǎn)物。4b)擴(kuò)增來(lái)自外周血樣品的cDNA序列使用實(shí)施例4a相同的步驟進(jìn)行對(duì)來(lái)自外周血樣品的cDNA序列(獲自實(shí)施例3b的cDNA)進(jìn)行擴(kuò)增。實(shí)施例5測(cè)序?qū)Ω鶕?jù)前面實(shí)施例獲得的序列進(jìn)行測(cè)序以進(jìn)行定量和定性分析。5.1)重鏈和輕鏈樣品處理挑取分別根據(jù)前面實(shí)施例4a和4b獲自冠狀動(dòng)脈斑塊樣品和外周血樣品的重鏈和輕鏈的克隆樣品以使用BigDye化學(xué)進(jìn)行測(cè)序并使用ABIPRISM3100測(cè)序儀進(jìn)行分析。使用ImMunoGeneTics中可得的數(shù)據(jù)庫(kù)(通過(guò)網(wǎng)站http://imgt.cines.fr可得)將所獲得的序列各自與種系片段比對(duì)，以分別對(duì)重鏈和輕鏈鑒定V，D，J以及V和J基因重現(xiàn)、與種系的同源性水平以及體細(xì)胞突變的程度。將CDR3的序列一致性用于鑒定克隆；如以上提到的，具有相同CDR3的序列被認(rèn)為來(lái)自相同的克隆。來(lái)自根據(jù)上文實(shí)施例4a獲得的冠狀動(dòng)脈斑塊樣品的重鏈的多聚核苷酸序列對(duì)應(yīng)于1-51、65-105、191-209、253-295、345-349、371-383和395-427中奇數(shù)號(hào)SequenceID且編碼對(duì)應(yīng)于2-52、66-106、192-210、254-296、346-350、372-384和396-428中偶數(shù)號(hào)SequencelD的氨基酸序列。來(lái)自根據(jù)上文實(shí)施例4a獲得的冠狀動(dòng)脈斑塊樣品的輕鏈的多聚核苷酸序列對(duì)應(yīng)于53-63、107-189、211-251、297-343、351-369、385-389和從429-453中奇數(shù)號(hào)SequenceID且編碼對(duì)應(yīng)于54-64、108-190、212-252、298-344、352-370、386-390和從430-454中偶數(shù)號(hào)SequenceID的氨基酸序列。5.2)球蛋白序列內(nèi)部參考對(duì)五個(gè)克隆的分析顯示所獲得的0-球蛋白序列與數(shù)據(jù)庫(kù)中存在的序列一致(見圖9，其報(bào)告了與標(biāo)準(zhǔn)球蛋白L48931的比對(duì))，這樣指出了沒(méi)有突變事件是由于過(guò)程變化導(dǎo)致的。5.3)來(lái)自冠狀動(dòng)脈斑塊樣品的輕鏈獲自根據(jù)實(shí)施例4a的冠狀動(dòng)脈斑塊樣品的克隆的分析結(jié)果在以下表I中顯示。對(duì)于每個(gè)克隆，V、D和J基因欄分別報(bào)告了被發(fā)現(xiàn)編碼重鏈的V，D和J可變部分的序列類型。同源性百分比指的是每條克隆自冠狀動(dòng)脈斑塊樣品的序列與上文公開的對(duì)應(yīng)種系序列之間同源性的百分比。表I5.4)來(lái)自冠狀動(dòng)脈斑塊樣品的重鏈對(duì)于根據(jù)實(shí)施例4a獲得的重鏈序列重復(fù)進(jìn)行與分析輕鏈序列所采用的相同的步馬聚o結(jié)果顯示于以下表II。表II5.5)來(lái)自外周血樣品的輕鏈對(duì)于獲自根據(jù)實(shí)施例4b獲得的外周血樣品的輕鏈序列重復(fù)上文公開的應(yīng)用于輕鏈分析的相同步驟。結(jié)果顯示于以下表III。表III5.6)來(lái)自外周血樣品的重鏈對(duì)于來(lái)自外周血樣品的重鏈序列重復(fù)相同的步驟，結(jié)果顯示于以下表IV。表IV因此，由于擴(kuò)增自斑塊的序列的克隆11、9、13和20顯示了與種系序列最高的分歧，所以選擇它們以與8號(hào)輕鏈一起表達(dá)。5.7)結(jié)果以上數(shù)據(jù)顯示來(lái)自冠狀動(dòng)脈斑塊樣品的重鏈和輕鏈分別都具有寡克隆模式以及特征性VDJ和VJ基因模式。此外，CDR3部分中的體細(xì)胞超突變對(duì)于冠狀動(dòng)脈斑塊樣品的重鏈和輕鏈比對(duì)于外周血樣品更頻繁；此外，來(lái)自冠狀動(dòng)脈斑塊樣品的輕鏈和重鏈序列發(fā)生更高數(shù)量的突變事件。5.8)突變譜系樹對(duì)根據(jù)先前實(shí)施例獲得的序列已經(jīng)繪制了譜系樹，目的是示例說(shuō)明通過(guò)免疫球蛋白可變區(qū)域(IGV)的體細(xì)胞超突變?cè)诿庖咔虻鞍椎目寺∠嚓P(guān)組內(nèi)的多樣化。5.8.1)譜系樹產(chǎn)生根據(jù)實(shí)施例5鑒定種系基因。通過(guò)使用nj算法和如Mega3軟件(http://WWW.megasoftware.net/)中實(shí)施的進(jìn)化p模型鑒定樹的分叉，其中使用種系序列作為樹的根。進(jìn)行手工校正以使根據(jù)序列目測(cè)檢查的拓?fù)鋵W(xué)最佳化。5.8.2)結(jié)果結(jié)果顯示與圖12和圖13。實(shí)施例6用來(lái)自冠狀動(dòng)脈斑塊樣品的序列以制備表汰系統(tǒng)以及轉(zhuǎn)化宿主細(xì)胞然后選擇輕鏈和重鏈的克隆用于轉(zhuǎn)染，具體而言，選擇冠狀動(dòng)脈斑塊樣品輕鏈的克隆8(對(duì)應(yīng)于SequenceIDn°53)和重鏈的克隆11、9、13和20(分別對(duì)應(yīng)序列IDn°21、43,51和37)以轉(zhuǎn)染入表達(dá)載體用于根據(jù)以下步驟制備可溶性Fab片段。將編碼根據(jù)上述實(shí)施例6所選擇的輕鏈且對(duì)應(yīng)于SequenceIDn°53的基因轉(zhuǎn)移至表達(dá)載體pRB/expr，依照的是Burioni等人Hum.Antibodies.2001；10(3-4)149-54中公開的步驟。Seq.IDn°53GAGCTCACGCAGTCTCCAGCCACCGTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTATTAGTTTCCACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGTCTCCTCATCTACGGAACATCCACCAGGGCCACTGGTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTCTGCGGTTTATTACTGTCAGCAGTATCATAACTGGCCTCCCCTCACTTTCGGCGGAGGGACC在包含編碼所選擇的輕鏈基因(選自實(shí)施例5中的克隆8)的表達(dá)載體中進(jìn)一步引入編碼對(duì)應(yīng)克隆11(對(duì)應(yīng)于SequenceIDn°21)的重鏈的基因，依照相同的Burioni等人HumAntibodies.2001；10(3-4):149_54公開的步驟。Seq.IDn°21CTCGAGTCTGGGGGAGGCTTGGGACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTTACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGATAGGGGGGAGAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGGGACAATTCTAAGAACACGCTGTATGTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCCTATATTTCTGCGCGAAAGATCAATTTCTATGGTTCGGGGAGTCAACAGCGGGTGATGCTTTTGATATCTGGGGCCAAGGGACA將表達(dá)載體引入大腸桿菌XL-1Blue以表達(dá)可溶性Fab。具體而言，在10ml具有氨芐青霉素(lOOng/ml，Sigma-Aldrich,圣路易斯，密蘇里)和四環(huán)素(10ng/ml，Sigma-Aldrich，圣路易斯，密蘇里)^SB(SuperBroth,Becton,Dickinson，新澤西)中接種來(lái)自新鮮平板的單個(gè)細(xì)菌菌落，在37°C下在定軌搖床中孵育過(guò)夜。之后，將2.5ml培養(yǎng)物接種至5升燒瓶中1升SB/amp-tet(上述SB、氨芐青霉素和四環(huán)素混合物)，生長(zhǎng)至光密度(0D_)為大約1.0。然后加入IPTG(異丙基-3-D-硫代半乳糖吡喃糖苷；Biorad，加尼弗尼亞)至終濃度為ImM，并在30°C下在定軌搖床中孵育細(xì)菌培養(yǎng)物過(guò)夜。這樣，將細(xì)菌在4°C下以3000rpm離心20分鐘，沉淀重懸于10mlPBS。接著加入50iUPMSF(來(lái)自100mM的儲(chǔ)備液)以抑制蛋白酶，并在冰上對(duì)細(xì)菌進(jìn)行三次超聲，每次運(yùn)行3分鐘。將細(xì)菌培養(yǎng)物在4°C下以18000rpm離心45分鐘，用0.22ym直徑的膜(Mi11ipore)小心過(guò)濾上清液。同時(shí)，用10倍體積的pbs洗滌柱子，隨后將過(guò)濾的上清液緩慢加至柱子。在用至少30倍體積的PBS洗滌之后，用100mM甘氨酸/HC1pH2.5洗脫Fab。收集10個(gè)級(jí)分(每個(gè)級(jí)分大約1ml)并立即用1MTris(pH9)中和。純化的Fab在SDS-PAGE膠中以非還原條件進(jìn)行測(cè)試，顯示了大約50kDa的單個(gè)條市o將相對(duì)條帶與至少兩種不同標(biāo)準(zhǔn)濃度BSA相比較以定量Fab。實(shí)施例7用來(lái)自動(dòng)脈粥樣化斑塊樣品的序列以制備表汰系統(tǒng)以及轉(zhuǎn)化宿主細(xì)胞重復(fù)與實(shí)施例6中所公開的相同步驟，將編碼克隆9的重鏈(對(duì)應(yīng)于SequenceIDn°43)的序列引入包含根據(jù)實(shí)施例5選擇的克隆8的輕鏈基因的表達(dá)載體。SeqIDn°43CTCGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGGCTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTGACTACTACATGAGTTGGATCCGCCAGGCTCCAGGGAAGGGGCTGGAATTTATATCATACATTAGTAGTGGTGGTGACACCATACACCACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAGAAGTCACTGTATCTCCAAATGAACAGCCTGAGAGTCGAGGACACGGCCGTATATTACTGTGCGTGCCGTGGGGTCTGGGGCCAGGGAACC實(shí)施例8用來(lái)自動(dòng)脈粥樣化斑塊樣品的序列以制備表達(dá)系統(tǒng)以及轉(zhuǎn)化宿主細(xì)胞重復(fù)與實(shí)施例6中所公開的相同步驟，將編碼克隆13的重鏈(對(duì)應(yīng)于SequenceIDn°51)的序列引入包含根據(jù)實(shí)施例5選擇的克隆8的輕鏈基因的表達(dá)載體。Seq.IDn°51CTCGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGCAGTGGTTACTACTGGACCTGGATCCGCCAGTACCCAGGGAGGGGCCTGGAGTGGATTGGATACATCTCTTACAGGGGGAGCACCTACTACAACCCGTCCCTCAAGAGTCGAGTTACAATATCACTAGACACGTCTAAGAACCAGTTTTTCTTGAACCTGACCTCTGTGACTGCCGCGGACACGGCCGTGTATTTCTGTGCGAGAGATCGGAGTAGAGCAACATCTGGTATTCTTGACTACTGGGGCCAGGGAACC實(shí)施例9用來(lái)自動(dòng)脈粥樣化斑塊樣品的序列以制備表達(dá)系統(tǒng)以及轉(zhuǎn)化宿主細(xì)胞重復(fù)與實(shí)施例6中所公開的相同步驟，將編碼克隆20的重鏈(對(duì)應(yīng)于SequenceIDn°37)的序列引入包含根據(jù)實(shí)施例5選擇的克隆8的輕鏈基因的表達(dá)載體。Seq.IDn°37CTCGAGTCGGGGGGAGGCTTCGTACAGCCTGGGGGGTCTCTGAGACTCTCCTGTGCAGC23CTCTGGATTCACCTTCAGGGACTATGCCATGGGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCCGGAGTGGGTCTCAATTATTAGTGCTAGTGGTGGTTCCATATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACACACTGTATCTGCAAATGAACAGTCTCAGAGCCGACGACACGGCTGTATACTACTGTGCAAGACAGACCAGCAGCAGATGGTATGATTGGTTCGACCCCTGGGGCCAGGGAACC實(shí)施例10免疫組織學(xué)測(cè)定新鮮的斑塊樣品在液氮中凍存，使用恒冷箱進(jìn)行切片。用冰冷的丙酮固定5ym厚的切片并用血清封閉液(2%serum,1%BSA、0.1%TritonX-100,0.05%Tween20)在室溫下封閉1小時(shí)。用根據(jù)本發(fā)明生產(chǎn)和鑒定的Fab以適當(dāng)?shù)南♂尪忍綔y(cè)經(jīng)固定的切片，室溫下孵育2小時(shí)。用PBS洗滌切片五次，加入FITC(異硫氰酸熒光素)-綴合的二級(jí)抗人FaMSigma-Aldrich，圣路易斯，密蘇里)的適當(dāng)稀釋液。室溫30分鐘后再次洗滌切片，并用熒光顯微鏡檢測(cè)這樣形成復(fù)合體配體/抗體。實(shí)施例11噬菌體文庫(kù)的抗體篩選根據(jù)制造商說(shuō)明書使用Fab-包被的高結(jié)合96-孔ELISA平板(Costar96w聚苯乙烯1/2面積平底HI-結(jié)合平底，cat#3690)進(jìn)行隨機(jī)噬菌體展示肽文庫(kù)的淘盤式篩選(Ph.D.-12噬菌體展示肽文庫(kù)試劑盒，目錄#E8110S，NewEnglandBiolabs，貝弗利，馬薩諸塞)，該文庫(kù)在絲狀噬菌體M13的cpIII衣殼蛋白N-末端表達(dá)十二肽。為了移除結(jié)合于抗體保守區(qū)域的噬菌體，通過(guò)在37°C下將擴(kuò)增的噬菌體與25yg人標(biāo)準(zhǔn)IgG庫(kù)(Endobulin、A.T.CJ06BA02、BaxterS.p.A.)結(jié)合1小時(shí)而從第二輪淘盤式篩選中進(jìn)行負(fù)篩選。如上文描述進(jìn)行四輪篩選，將擴(kuò)增的噬菌體在根據(jù)本發(fā)明生產(chǎn)和鑒定的Fab上進(jìn)行淘盤式篩選，相同的標(biāo)準(zhǔn)IgG庫(kù)用于負(fù)選擇。實(shí)施例12肽篩選及DNA序列分析所有從實(shí)施例11中獲得的噬菌體用來(lái)感染大腸桿菌菌株ER2537，隨機(jī)挑取的單個(gè)斑塊在根據(jù)本發(fā)明生產(chǎn)和鑒定的Fab以及標(biāo)準(zhǔn)IgG庫(kù)上進(jìn)行酶聯(lián)免疫測(cè)定。洗滌抗原包被的平板(Costar96w聚苯乙烯1/2面積平底HI-結(jié)合平底，cat#3690)并用PBS/BSA溶液在37°C下封閉1小時(shí)；加入50u1噬菌體(108個(gè)噬菌體每毫升)并在37°C下孵育2小時(shí)。用PBS(0.l%Tween-20；Sigma-Aldrich，圣路易斯，密蘇里)將平板洗滌10次；之后,加入50ii1的HRP-綴合的抗M13抗體(GEHealthcare27-9411-01)在PBS中13000的稀釋液。在37°C下2小時(shí)后，用PBS(0.5%Tween-20；Sigma-Aldrich，圣路易斯，密蘇里)洗滌平板，通過(guò)加入100ill底物(Sigma-Aldrich，圣路易斯，密蘇里)檢測(cè)特定的結(jié)合噬菌體，在室溫下30分鐘后讀出平板的450nm光密度。將在根據(jù)本發(fā)明的Fab上顯示(》45(1值>1，在IgG庫(kù)上顯示(45(1值<0.3的陽(yáng)性克隆評(píng)分為陽(yáng)性，并通過(guò)使用軟件P印itopehttp://p印Hope.tau.ac.il/index.html的序列分析而進(jìn)行評(píng)估。從肽序列分析鑒定出保守的氨基酸，基于序列中存在的保守殘基的量選擇了四種肽。已經(jīng)鑒定出四種肽并且相關(guān)序列對(duì)應(yīng)于391-394的SequenceID。實(shí)施例13酶聯(lián)免疫吸附測(cè)定Hep-2(ATCCCCL-23)細(xì)胞在補(bǔ)充有抗生素/抗真菌溶液(Invitrogen，抗生素/抗真菌溶液，液體15240-062)和10%FBS的E_Mem(Invitrogen0820234DJ)中生長(zhǎng)。細(xì)胞規(guī)則地每5天以110分組。五百萬(wàn)個(gè)細(xì)胞在PBS中進(jìn)行洗滌并用RIPA緩沖液(50mMTrisHCLph8+150mMNaCl+1%NP-40+0.5%NAdeossicolate+0.1%SDS)進(jìn)行裂解。用H印-2裂解物的系列稀釋液包被(PBS中1000ng、200ng、40ng和8ng)Elisa平板(Costar96w聚苯乙烯1/2面積平底HI-結(jié)合平底，cat#3690)，4°C過(guò)夜。在37°C下用PBS+BSA3%封閉2小時(shí)后，F(xiàn)ab24的系列稀釋液(20ug/mlUOug/ml,5ug/ml,2.5ug/ml)與包被的抗原在37°C下孵育1小時(shí)。在用PBS+Tween200.1%(SIGMAcod.PL379)洗滌后，平板與人IgG過(guò)氧化物酶(SIGMAcod.A2290)在37°C下孵育30分鐘。用PBS+Tween0.洗滌之后，將TMB底物加入孔中(PIERCETMB過(guò)氧化物酶底物試劑盒cod.SK4400)。450nm處用分光光度計(jì)分析ELISA平板。結(jié)果顯示于圖14。實(shí)施例14肽合成14.1)概述化學(xué)試劑，化學(xué)結(jié)構(gòu)部分以及技術(shù)的縮寫AA_氨基酸、AcOH-乙酸、ACN-乙腈、API-ES-大氣壓離子化電噴射、Btn-生物素、Boc-叔丁氧羰基、DCM-二氯甲烷、DIC-N，N-二異丙基碳化二亞胺、DIEA-N,N-二異丙基乙胺、DMF-N,N-二甲基亞砜、Et20-二乙醚、Fmoc-9-芴甲氧羰基、Adoa-8-氨基-3，6-二氧雜辛酸、HFIP-1，1,1,3,3,3-六氟-2-丙醇、H0Bt-N-羥基苯并三唑、MeOH-甲醇、Neg.ion-陰性離子、NHS-N-羥基琥珀酰亞胺、NMP-N-甲基吡咯烷酮、Pip-哌啶、Pos.ion-陽(yáng)性離子、HBTU-0-(苯并三氮唑基)_N，N，N，，N，-四甲基脲六氟磷酸、PyBOP-苯并三唑-1-基-氧-三-吡咯烷-磷六氟磷酸、tE-保留時(shí)間(分鐘)、試劑B(88552-TFAH20苯酚:TIPS-v/v/wt/v)、Su_琥珀酰亞胺、TFA-三氟乙酸、TIPS-三異丙醇硅烷、H20-水。用于合成多種肽用到的胺和非天然氨基酸名稱、結(jié)構(gòu)和縮寫在表V中給出。用于反應(yīng)、色譜純化和HPLC分析的溶劑為E.MerckOmni級(jí)溶劑，來(lái)自VWR公司(WestChester，PA)。NMP和DMF購(gòu)自PharmcoProductsInc.(Brookfield，CT)，并且為肽合成級(jí)或低水/無(wú)胺Biotech級(jí)品質(zhì)。哌啶(測(cè)序級(jí)，復(fù)餾99+%)和TFA(分光光度級(jí)或測(cè)序級(jí))購(gòu)自Sigma-Aldrich公司(密爾沃基，WI)或購(gòu)自Sigma-Alrich公司Fluka化學(xué)部。苯酚(99%)、DIEA、DIC和TIPS購(gòu)自Sigma-Aldrich公司。所使用的Fmoc-保護(hù)氨基酸、PyBop和HOBt購(gòu)自Nova-Biochem(圣地亞哥，CA，美國(guó))、AdvancedChemTech(路易斯維爾，KY，美國(guó))、Chem_ImpexInternational(WoodDale111,USA)禾口MultiplePeptideSystems(SanDiego,CA,USA)。Fmoc-Adoa和Btn-Adoa-Adoa-OH獲自NeoMPSCorp(圣地亞哥，CA)。分析性HPLC數(shù)據(jù)一般使用ShimadzuLC-10ATVP雙泵梯度系統(tǒng)獲得，其中采用了WatersX-Terr.aMS-C18(5.Oil，50X4.6mm；120A孑L徑)或WatersSunfire0BD-C8(4.6X50mm3.5y，120人孔徑)的柱子及梯度或等度洗脫系統(tǒng)，使用H20(0.1%TFA)作為洗脫劑A，ACN(0.1%TFA)為洗脫劑B。使用220和/或230nm處的UV完成化合物的檢測(cè)。制備性HPLC在配有裝了制備性流式細(xì)胞的SPD-10AVUV檢測(cè)器的ShimadzuLC-8A雙泵梯度系統(tǒng)上進(jìn)行。一般地，將含有粗肽的溶液加載到反相WatersSunfireOBDC8(50X250mm;粒度10.0y，120人孔徑)柱子上，使用連接于制備性LC-8A雙泵梯度系統(tǒng)的第三個(gè)泵。在將粗產(chǎn)品混合物的溶液應(yīng)用于制備性HPLC柱子之后，反應(yīng)溶劑及作為稀釋劑應(yīng)用的溶劑如DMF或DMS0在低有機(jī)相組合物條件下從柱子上洗脫。然后使用洗脫劑B至洗脫劑A的梯度洗脫將所需的產(chǎn)品洗脫。含有產(chǎn)品的級(jí)分基于其用分析性HPLC和質(zhì)譜分析確定的純度進(jìn)行合并。將合并的部分凍干以提供所需的產(chǎn)品。在AgilentLC-MSD1100質(zhì)譜儀上內(nèi)部獲得質(zhì)譜數(shù)據(jù)。對(duì)于級(jí)分選擇和產(chǎn)品定性的目的，通常使用API-ES在陽(yáng)性離子模式中獲得質(zhì)譜值。一般地，靶標(biāo)肽的分子量為2000;質(zhì)譜通常顯示強(qiáng)的二倍或三倍正電離子質(zhì)量值而不是弱的[M+H]+。一般采用這些用于選擇級(jí)分進(jìn)行收集和合并以從HPLC純化中獲得純肽。14.2)用于固相肽合成(SPPS)的一般方法14.2.1)通過(guò)公認(rèn)的自動(dòng)化操作流程在RaininptiSymphony肽合成儀上合成線性肽(十二條肽序列/合成)，其中使用Fmoc-Pal-Peg-PS樹脂(0.2mmol/g)和/或合適地預(yù)裝的樹脂，F(xiàn)moc-保護(hù)氨基酸和DMF中的PyBop-介導(dǎo)的酯激活。將剩余的肽序列通過(guò)SPPS方法一步步加載到Fmoc-Pal-Peg-PS和/或其他樹脂上，典型地為0.2mmol的規(guī)模。以在DMF中PyBop-DIEA試劑激活的4倍過(guò)量的每種氨基酸進(jìn)行氨基酸偶聯(lián)。生物素用4-倍過(guò)量的Btn-NHS酯偶聯(lián)到肽的N-末端。14.2.2)當(dāng)使用三苯甲基樹脂上預(yù)加載的二胺時(shí)，最后的乙?；笥?:1:1-DCMAcOHHFIP將整條受保護(hù)肽鏈從樹脂上裂解下來(lái)，在揮發(fā)物蒸發(fā)之后，在溶液中將最終的Btn-Adoa-Adoa偶聯(lián)到胺的C-末端。在RT下，粗的完全保護(hù)肽在溶液中用預(yù)形成的Btn-Adoa-Adoa-NHS酯的1.0等價(jià)物處理16h(總體積5.0mL/g的粗重量)。在給定氨基酸的典型偶聯(lián)過(guò)程中，6.OmL含有0.8mmol氨基酸的DMF溶液，接著是PyBOP(0.8mmol,DMF溶液，1.25mL)和DIEA(0.8mmol,DMF溶液，1.25mL)以自動(dòng)化的操作流程接連加入含有樹脂(0.2mmol)的反應(yīng)容器(RV)，用反復(fù)的氮?dú)鈿馀輸嚢铇渲?小時(shí)后用DMF(4.5mL，6X)將樹脂透徹洗滌，并使用溶于DMF(4.5mL)的25%Pip切割Fmoc-基團(tuán)10分鐘，接著用相同試劑進(jìn)行第二次處理10分鐘，以保證完全去保護(hù)。樹脂再次用DMF(5mL/g，6X)透徹洗滌；在DMF洗滌之間進(jìn)行DCM(10mL/g)洗滌以保證樹脂沒(méi)有殘留的Pip。肽合成之后，帶有完全保護(hù)肽的樹脂用試劑B(10.0mL/g樹脂或10.0mL/g粗的保護(hù)肽)切割4小時(shí)。揮發(fā)物在真空下移除得到膏狀物。這樣得到的膏狀物與Et20—并研碎以得到固體，將所述固體通過(guò)離心沉淀下來(lái)，接著再進(jìn)行3輪Et20洗滌和沉淀。所得的固體在真空下干燥以提供粗肽。麗2000的肽的200umol規(guī)模的合成給出200_300mg(理論值的90-110%)的粗肽。超過(guò)理論的產(chǎn)量最可能是由于潮濕和殘留溶劑。14.3)肽的純化_一般步驟在“協(xié)奏”的儀器上進(jìn)行漏2000的肽的200umol規(guī)模的合成于每個(gè)反應(yīng)容器(RV)提供了200-300mg的粗肽。粗肽(200_500mg)通過(guò)反相HPLC在一次運(yùn)行中進(jìn)行純化。溶于ACN(lOml)的粗肽(200mg)用H20稀釋到終體積50mL，對(duì)溶液進(jìn)行過(guò)濾。將過(guò)濾的溶液加載到已經(jīng)用溶于H20的10%ACN(0.1%TFA)預(yù)平衡的制備性HPLC柱子(Waters,SunfirePrepC8,50X250mm10u,120A)上。將溶液應(yīng)用于柱子上期間，停止來(lái)自制備性HPLC系統(tǒng)的平衡洗脫劑流。將溶液應(yīng)用于柱子之后，重新開始來(lái)自制備性HPLC系統(tǒng)的平衡洗脫劑流，洗脫劑組合物隨后轉(zhuǎn)換為20%ACN-H20(0.1%TFA)以10.0分鐘，此后開始速率為0.5%/分鐘ACN(0.1%TFA)進(jìn)入H20(0.1%TFA)的線性梯度洗脫，并且維持60分鐘。使用220nm處的UV作為產(chǎn)物洗脫指示來(lái)收集級(jí)分(15mL)。所收集的級(jí)分在分析性反相C8柱子(WatersSunfire0BD-C8，4.6X50mm,5u,12OA)上進(jìn)行分析，合并并凍干純度>95%的含有產(chǎn)物的級(jí)分以提供對(duì)應(yīng)的肽。分離之后，用HPLC和質(zhì)譜分析這些肽證實(shí)一致性和純度。肽的數(shù)據(jù)在表VI(序列，樹脂加載和產(chǎn)量)，表VII(HPLC和質(zhì)譜分析)和表VIII(肽結(jié)構(gòu))中提供。實(shí)施例15酶聯(lián)免疫吸附測(cè)定以重懸于PBS中的lOOng肽在4°C包被Elisa平板(Costar96w聚苯乙烯1/2面積平底HI-結(jié)合平底，cat#3690)過(guò)夜。用PBS+BSA(3%)在37°C下封閉2小時(shí)后，F(xiàn)ab24(20iig/ml)與包被的抗原在37°C孵育1小時(shí)。用PBS+Tween200.1%(SIGMAcod:PL379)洗滌后，在37°C將平板與抗人IgG過(guò)氧化物酶(SIGMAcod:A2290)孵育30分鐘。用PBS+Tween0.洗滌后，向孔內(nèi)加入TMB底物(PIERCETMB過(guò)氧化物酶底物試劑盒codSK4400)。在450nm處用分光光度計(jì)分析ELISA平板。結(jié)果顯示于圖15。表V-縮寫和結(jié)構(gòu)表VI-肽序列、樹脂加載和產(chǎn)量表VII-肽的HPLC和質(zhì)譜分析〔0352l100105110ValTrpGlyGinGlyThr115SequenceID5ctcgaggagtctgggggaggcttggtccagcctggggggtccctgaaactctcctgtgca60gcctctgggttcgccttcagtggctctgctctgcactgggtccgccaggcttccgggaga120gggctggagtgggttggccgtattagaaccaaagctaacaattacgcgacagtgtatggt180gcgtcggtgaagggcaggttcaccatctccaaagacaatgccaagaactcactgtatctg240caaatgaacagcctgagagccgaggacacggctgtgtattactgtgcgagactgcttggc300actggctggtacggagttgactactggggccagggaac338SequenceID6LeuGluGluSerGlyGlyGlyLeuValGinProGlyGlySerLeuLys855243A1LeuSerCys5AlaAla20GinAlaSerTrpValArg35LysAlaAsnAsnSerGlyPheGlyArgThr50ArgPheThrlieGly65GinMetAsnSerArgLeuLeuThrSequenceIDGly100Leu85ThrSer70ArgArg40AlaThrAspAsnAlaGluAsp10AlaPhe25GlyLeuGluTrpSerGlySerAla30Gly15LeuHisTyr55LysValTyrAlaLys75AlaGly60AsnVal45AlaArglieSerValLysSerLeuTyrGlyTrpTyrGly105Thr90ValAspTyrValTyrTyrTrpGly110Cys95GinLeu80AlaGlyctcgagtcggggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcc60tctggattcacctttagcagctatgccgtgagctgggtccgccaggctccagggaagggg120ctggagtgggtctcagctattagtggtagtggtggtagcacatattacgcagacttagtg180aagggccggttcgccatctccagagacaattccaagaacacgctgtatctgcaaatgaac240agcctgagagccgaggacacggccgtatattactatgcgaaagatcaaatgaacttaccg300tacaactggttcgacccctggggccagggaacc333SequenceID8LeuGluSerGlyGlyGlyLeuVal15SerCysAlaAlaSerGlyPheThr20ValArgGinAlaProGlyLysGlyGinProGlyGlySerLeuArgLeu1015PheSerSerTyrAlaValSerTrp2530LeuGluTrpValSerAlalieSerGlyThrSequenceID15ctcgaggagtctgggggaggcttggtcaagcctggagggtccctgaggctctcctgtgca60gcctctggattcaccttcagtgactactacatgagttggatccgccaggctccagggaag120gggctggaatttatatcatacattagcagtggtggtgacaccatacaccacgcagactct180gtgaagggccgattcaccatctccagggacaacgccaagaagtcactgtatctccaaatg240aacagcctgagagtcgaggatacggccgtatattactgtgcgtgccgtggggtctggggc300cagggaacc309SequenceID16LeuGluGluSerGlyGlyGlyLeuValLysProGlyGlySerLeuArg1LeuSerCysTrplieSerPhe65AsnSer50ThrArg35Gly5AlaAla20GinAlaProSerGlyGlyPheThr25Gly10PheSerAspTyrGlyAspThrlieSerArgLys40Hislie55AsnAlaSerLeuArgVal85GinAsp70GluAspThrGlyThrLeuHisAlaLysGluPheAspLysAlaVal90Ser75TyrSer60Leulie45ValTyr30Ser15MetSerTyrTyrCysAlaTyrlieLysGlyArgLeuGinCys95Met80ArgGlyValTrpGly100SequenceID17ctcgaggagtcatggggaggcttggtcaaggcctctggattcaccttcagtgactactacgggctggaatttatatcatacattagtagtgtgaagggccgattcaccatctccagggacaacagcctgagagtcgaggacacggccgtacagggaacc18cctggagggtccctgaggctctcctgtgcaatgagttggatccgccaggctccagggaagggtggtgacaccatacaccacgcagactctaacgcccagaagtcactgtatctccaaatgtattactgtgcgtgccgtggggtctggggcSequenceIDLeuGluGluSer1LeuSerCysTrplieSerSer50Arg35GlyAla20GinTrp5AlaGlyGlyLeuValSerGlyPheAlaProGlyLys10PheGlyAspThrlie55Lys40HisThr25GlyLeuGluHisAlaAspProGlySerAspPheGlySerTyrSer60lie45ValTyr30SerLeuArg15MetSerTyrLysGlylieArg6012018024030030941PheThrlieSerArgAspAsnAlaGinLysSerLeuTyrLeuGinMet65707580AsnSerLeuArgValGluAspThrAlaValTyrTyrCysAlaCysArg859095GlyValTrpGlyGinGly100SequenceID19ctcgagtcggggggaggcttggtccagcctggggggtccctgaaactctcctgtgcagcctctgggttcgccttcagtggctctgctctgcactgggtccgccaggcttccgggagagggctggagtgggttggccgtattagaaccaaagctaacaattacgcgacagtgtatggtgcgtcggtgaagggcaggttcaccatctccagagatgattcaaagagcacggcgtatctgctaatgaacagcctgaaaaccgaggacacggccgtctattactgtactagttatgataccagctatgataggagtggttattatttgaactactggggccagggaaccSequenceID20LeuGluSerGlyGlyGlyLeuValGinProGlyGlySerLeuLysLeu1SerCysAlaAla20AlaGly5SerValArgGin35AlaAsnAsnTyrGlyLeuValGinGlyPheAlaSerGlyArgThrLys50PheGly40ThrPro10PheSer25LeuGluGlyGlySerLeuGlySerAlaArg65MetAsnSerLeuThrlieSerArg70LysThr85Ala55AspAspSerLysGluAspThrAla90TrpValValTyrGlyGly45SerLeu30ArgLys15HisTrplieArgValLysGlySer75ValAla60ThrAlaTyrLeuTyrTyrCysThr95Leu80SerSequenceID22LeuGluSerGlyGlyGlyLeuGlyGinProGlyGlySerLeuArgLeu60120180240300345TyrAspThrSerTyrAspArgSerGlyTyrTyrLeuAsnTyrTrpGly100105110GinGlyThr115SequenceID21ctcgagtctgggggaggcttgggacagcctggggggtccctgagactctcctgtgcagcc60tctggatttacctttagcagctatgccatgagctgggtccgccaggctccagggaagggg120ctggagtgggtctcagctattagtgataggggggagagcacatactacgcagactccgtg180aagggccggttcaccatctccagggacaattctaagaacacgctgtatgtgcaaatgaac240agcctgagagccgaggacacggccctatatttctgcgcgaaagatcaatttctatggttc300ggggagtcaacagcgggtgatgcttttgatatctggggccaagggaca348421SerValAspThr65SerCysArg5SerAlaAla20AlaProArq50lieGin35GlyGluSerArgAspLeuArgAlaGlu85GlyPheGlyLysSerThrTyr55AsnSer70AspThrThrPhe25GlyLeu40TyrAlaLysAsnAlaLeu10SerGluAspSerThrSerTyrAlaTrpValSer45LysMet30Ala15SerTrpTyr90Leu75PheVal60TyrValGlyGinMetCysAlaLysAsp95lieSerArgPheAsn80GinPheLeuTrpPheGlyGluSerThrAlaGlyAspAlaPheAsplieTrp100105110GlyGinGlyThr115SequenceID23ctcgagtcgggcccaggactggtgaagccttcacagaccctgtccctcacctgcactgtc60tctggtggctccatcagcagtggttactactggacctggatccgccagtacccagggagg120ggcctggagtggattggatacatctcttacagggggagcacctactacaacccgtccctc180aagagtcgagttacaatatcactagacacgtctaagaaccagtttttcttgaacctgacc240tctgtgactgccgcggacacggccgtgtatttctgtgcgagagatcggagtagagcaaca300tctggtattcttgactactggggccagggaacc333SequenceIDLeuGluSer1ThrCysThrTrplieSerThr65SerTyr50lieArg35Arg24GlyVal20GinPro5SerGlyLeuValLysGlyGlyTyrProGlyPro10SerGlySerThrValSerArgSerLeuAspThr70AspTyr55SerSerlie25ArgGly40TyrAsnProSerSerGinThrLeuSerGlyTyrLeuGluTrpThrAlaAlaAla85SerThrGlylieLysAsnGinAlaValPhe75PheLeuAsp105Tyr90TyrTrpLeu60PheCysGlylie45LysTyr30GlySerLeu15TrpTyrSerArgLeuAsnLeuArgAlaGinGly110Asp95ThrThrlieValThr80ArgThr100SequenceID25ctcgaggagtcagggggaggtgtggtacagccagggcggtccctgagactcccctgtaca60SerLeuArgAlaGhAspThrAlaValTyrTyrCysAlaAsnArgPro859095ValArgGlyValAspTyrPheAspTyrTrpGlyGinGly100105Sequence工D29ctcgaggagtctgggggaggcttggtcaagcctggagggtccctgaggctctcctgtgca60gcctctggattcaccttcagtgactactacatgagttggatccgccaggctccagggaag120gggctggaatttatatcatacattagtagtggtggtgacaccatacaccacgcagactct180gtgaagggccgattcaccatctccagggacaacgccaagaagtcactgtatctccaaatg240aacagcctgagagtcgaggacacggccgtatattactgtgcgtgccgtggggtctggggc300cagggaacc309Sequence工D30LeuGhGhSetGlyGlyGlyLeuValLysProGlyGlySetLeuArgl5lo15LeuSetCysAlaAlaSetGlyPheThrPheSetAspTyrTyrMetSet202530TrpIleArgGlnAlaProGlyLysGlyLeuGhPheIleSetTyrIle354045SetSetGlyGlyAspThrIleHiSHiSAlaAspSetValLysGlyArg505560PheThrIleSetArgAspAshAlaLysLysSetLeuTyrLeuGlnMet65707580AshSetLeuArgValGhAspThrAlaValTyrTyrCysAlaCysArg859095GlyValTrpGlyGlnGlyThr100Sequence工D3lctcgagtcggggggaggcttggtccagcctggggggtccctgaaactctcctgtgcagcc60tctgggttcgccttcagtggctctgctctgcactgggtccgccaggcttccgggagaggg120ctggagtgggttggccgtattagaaccaaagctaacaattacgcgacagtgtatggtgcg180tcggtgaagggcaggttcaccatctccagagatgattcaaagagcacggcgtatctgcta240atgaacagcctgaaaaccgaggacacggccgtctattactgtactagttatgataccagc300tatgataggagtggttattatttgaactactggggccagggaacc345Sequence工D32LeuGhSerGlyGlyGlyLeuValGlnProGlyGlySetLeuLysLeu]l5lo15SetCysAlaAlaSetGlyPheAlaPheSetGlySetAlaLeuHiSTrp202530ValArgGlnAlaSetGlyArgGlyLeuGhTrpValGlyArgIleArg0715]3540450716]ThrLysAlaAsnAsnTyrAlaThrValTyrGlyAlaSerValLysGly0717]5055600718]ArgPheThrlieSerArgAspAspSerLysSerThrAlaTyrLeuLeu0719]657075800720]MetAsnSerLeuLysThrGluAspThrAlaValTyrTyrCysThrSer0721]8590950722]TyrAspThrSerTyrAspArgSerGlyTyrTyrLeuAsnTyrTrpGly0723]1001051100724]GinGlyThr0725]1150726]SequenceID330727]ctcgaggagtcaggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaag600728]gcttctggaggcaccttcagcagttatgctatcagctgggtgcgacaggcccctggacaa1200729]gggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaag1800730]ttccagggcagagtcacgaltaccgcggacaaatccacgagcacagcctacatggagctg2400731]agcagcctgagatctgaggacacggccgtgtattactgtgcgagagatcgaagtggggtt3000732]cttcgaagcagctcgccgalatggtacttcgatctctggggccgtggcacc3510733]SequenceID340734]LeuGluGluSerGlyAlaGluValLysLysProGlySerSerValLys0735]1510150736]ValSerCysLysAlaSerGlyGlyThrPheSerSerTyrAlalieSer0737]2025300738]TrpValArgGinAlaProGlyGinGlyLeuGluTrpMetGlyGlylie0739]3540450740]lieProliePheGlyThrAlaAsnTyrAlaGinLysPheGinGlyArg0741]5055600742]ValThrlieThrAlaAspLysSerThrSerThrAlaTyrMetGluLeu0743]657075800744]SerSerLeuArgSerGluAspThrAlaValTyrTyrCysAlaArgAsp0745]8590950746]ArgSerGlyValLeuArgSerSerSerProlieTrpTyrPheAspLeu0747]1001051100748]TrpGlyArgGlyThr0749]1150750]SequenceID350751]ctcgaggagtcagggggaggcgtggtccagcctgggaggtccctgagactctcctgtgca600752]gcgtctggattcagtttcagtaactatggcatgcactgggtccgccaggctccaggcaag1200753]ggactggagtgggtggcagttatatggcatgatggaagtaataaagactatggcgactcc18046gtgaagggccgattcagcatctccagagacaattccaggagaacgttgtatctgcaaatg240aacaacttgagagccgaggacacggctatatactactgtgcgagagaggggggttaccga300aacgtcgcggatatattgcgccccccacctgatgcttttgataactggggccaggggaca360SequenceID36LeuGluGluSerGlyGlyGlyValValGinProGlyArgSerLeuArg151015LeuSerCysAlaAlaSerGlyPheSerPheSerAsnTyrGlyMetHis202530TrpValArgGinAlaProGlyLysGlyLeuGluTrpValAlaVallie354045TrpHisAspGlySerAsnLysAspTyrGlyAspSerValLysGlyArg505560PheSerlieSerArgAspAsnSerArgArgThrLeuTyrLeuGinMet65707580AsnAsnLeuArgAlaGluAspThrAlalieTyrTyrCysAlaArgGlu859095GlyGlyTyrArgAsnValAlaAsplieLeuArgProProProAspAla100105110PheAspAsnTrpGlyGinGlyThr115120SequenceID37ctcgagtcggggggaggcttcgtacagcctggggggtctctgagactctcctgtgcagcc60tctggattcaccttcagggactatgccatgggctgggtccgccaggctccagggaagggg120ccggagtgggtctcaattattagtgctagtggtggttccatatactacgcagactccgtg180aagggccgattcaccatctccagagacaacgccaagaacacactgtatctgcaaatgaac240agtctcagagccgacgacacggctgtatactactgtgcaagacagaccagcagcagatgg300tatgattggttcgacccctggggccagggaacc333SequenceID38LeuGluSerGlyGlyGlyPheValGinProGlyGlySerLeuArgLeu151015SerCysAlaAlaSerGlyPheThrPheArgAspTyrAlaMetGlyTrp202530ValArgGinAlaProGlyLysGlyProGluTrpValSerlielieSer354045AlaSerGlyGlySerlieTyrTyrAlaAspSerValLysGlyArgPhe505560ThrlieSerArgAspAsnAlaLysAsnThrLeuTyrLeuGinMetAsn65707580SerLeuArgAlaAspAspThrAlaValTyrTyrCysAlaArgGinThr0793079407950796079707980799080008010802080308040805080608070808080908100811081208130814081585SerSerArgTrpTyrAspTrpPhe100SequenceID39ctcgaggagtctggggctgaggtgaagaaggcttctggagaccactatggtatcaactggtggatgggcggtatcatccctgtctttggcagagccaccattaccgcggacgactccacgacatttgacgacacggccgtctatttctgtggcggtaaagccctctccccctgggactacSequenceID40LeuGluGluSer9095AspProTrpGlyGinGlyThr105110cctgggtcctcggtgaaggtctcctgcaaggtgcgacaggcccctggacaagggcttgagacaactacctacgcacagaagttccagggcgggacggcctttttggagctgaccagactggcgacacctcaccaactgcatgtcctccggtggggccagggaacc1ValSerCysGinAlaPheThr65ThrGly50AlaPro35ThrLys20GlyGlyAlaGlu5AlaSerGlyValLysAspGinGlyLeuThrThrTyrGlu40GinHis25TrpAspPheAspAspSerAspThr85Thr70AlaAla55GlyThrLysAlaValTyrPheLys10TyrMetPhePheCys90ProGlySerSerlieAsnGlyGlyGlyGinLeu75AlaGly60Glulie45ArgTrp30lieAlaLeuThrValLys15ValArgProVallieThrProHisThrArgGin95Leu80Leu60120180240300345HisValLeuArgGlyGlyLysAlaLeuSerProTrpAspTyrTrpGly100105110GinGlyThr115SequenceID41ctcgaggagtctggggctgaagtgaagaagccggggtcctcggtgaaggtctcctgcacg60gcttctggaggcatcttcagcaattatgctgtcatctgggtgcgacaggcccctggacaa120gggcttgaatggatgggagggttcatccccatgtttgatacagcaaaccacgcacagcac180ctccagggcagagtcacgatcaccgcgggcgattccacgagcgtcgtctatctggaactg240cgcagcctgagatctgaagacaccgccatatatttttgcgcggcagccaaattgcaccct300aactggaactttggaactttctactttgactcctggggccagggaacc348SequenceID42LeuGluGluSerGlyAlaGluValLysLysProGlySerSerValLys151015ValSerCysThrAlaSerGlyGlyliePheSerAsnTyrAlaVallie202530TrpValArgGinAlaProGlyGinGlyLeuGluTrpMetGlyGlyPhe354045lieProMetPheAspThrAlaAsnHisAlaGinHisLeuGinGlyArg505560ValThrlieThrAlaGlyAspSerThrSerValValTyrLeuGluLeu65707580ArgSerLeuArgSerGluAspThrAlalieTyrPheCysAlaAlaAla859095LysLeuHisProAsnTrpAsnPheGlyThrPheTyrPheAspSerTrp100105110GlyGinGlyThr115SequenceID43ctcgagtctgggggaggcttggtcaagcctggagggtccctgaggctctcctgtgcagcc60tctggattcaccttcagtgactactacatgagttggatccgccaggctccagggaagggg120ctggaatttatatcatacat:tagtagtggtggtgacaccatacaccacgcagactctgtg180aagggccgattcaccatctc:cagggacaacgccaagaagtcactgtatctccaaatgaac240agcctgagagtcgaggacac:ggccgtatattactgtgcgtgccgtggggtctggggccag300ggaacc306SequenceID44LeuGluSerGlyGlyGlyLeuValLysProGlyGlySerLeuArgLeu151015SerCysAlaAlaSerGlyPheThrPheSerAspTyrTyrMetSerTrp202530lieArgGinAlaProGlyLysGlyLeuGluPhelieSerTyrlieSer354045SerGlyGlyAspThrlieHisHisAlaAspSerValLysGlyArgPhe505560ThrlieSerArgAspAsnAlaLysLysSerLeuTyrLeuGinMetAsn65707580SerLeuArgValGluAspThrAlaValTyrTyrCysAlaCysArgGly859095ValTrpGlyGinGlyThr100SequenceID45ctcgagtcggggggagacttggtacagcctggcgggtccctgagactctcctgtgtagcc60tctggattcacttttgatgattatgccatgcactgggtccggcagactccagggaagggc120ctggagtgggtctcaggtat；aagttggagaagtgattacagaggctatgcggactctgtg180aagggccgattcaccatctc:cagagacaacgccaagaactccctgtatcttcaaatgaac240gagctcacgcagtctccagccaccgtgtctgtgtctccaggggaaagagccaccctctcc60tgcagggccagtcagagtattagtttccacttagcctggtaccagcagaaacctggccag120gctcccaggctcctcatctatggggcatccaccagggccactggtatcccagccaggttc180agtggcagtgggtctgggacagagttcactctcaccatcagcagcctgcagtctgaagat240tctgcggtttattactgtcagcagtatcataactggcctcccctcactttcggcggaggg300acc303SequenceID56GluLeuThrGinSerProAlaThrValSerValSerProGlyGluArg52202530[1028]GlyGinAlaProArqLeuLeulieTyrGlyAlaSerThrArgAlaThr[1029]354045[1030]GlylieProAlaArgPheSerGlySerGlySerGlyThrGluPheThr[1031]505560[1032]LeuThrlieSerSerLeuGinSerGluAspSerAlaValTyrTyrCys[1033]65707580[1034]GinGinTyrHisAsnTrpProProLeuThrPheGlyGlyGlyThr[1035]859095[1036]SequenceID61[1037]ccagccaccgtgtctgtgtctccaggggaaagagccaccctctcctgcagggccagtcag60[1038]agtgttagcagtaacttagcctggtaccagcagaaacgtggccaggctcccagtctcctc120[1039]atctacggaacatctaccagggccactggtatcccagccaggttcagtggcagtgggtct180[1040]gggacagagttcactctcaccatcagcagcctgcagtctgaagattctgcggtttattac240[1041]tgtcagcagtatcataactggcctcccctcactttcggcggagggacc288[1042]SequenceID62[1043]ProAlaThrValSerValSerProGlyGluArgAlaThrLeuSerCys[1044]151015[1045]ArgAlaSerGinSerValSerSerAsnLeuAlaTrpTyrGinGinLys[1046]202530[1047]ArgGlyGinAlaProSerLeuLeulieTyrGlyThrSerThrArgAla[1048]354045[1049]ThrGlylieProAlaArgPheSerGlySerGlySerGlyThrGluPhe[1050]505560[1051]ThrLeuThrlieSerSerLeuGinSerGluAspSerAlaValTyrTyr[1052]65707580[1053]CysGinGinTyrHisAsnTrpProProLeuThrPheGlyGlyGlyThr[1054]859095[1055]SequenceID63[1056]ccagccaccgtgtctgtgtctccaggggaaagagccaccctctcctgcagggccagtcag60[1057]agtattagtttccacttagcctggtaccagcagaaacctggccaggctcccagtctcctc120[1058]atctacggaacatctaccagggccactggtatcccagccaggttcagtggcagtgggtct180[1059]gggacagagttcactctcaccatcagcagcctgcagtctgaagattttgcagtttattac240[1060]tgtcagcagtatcataactggcctcccctcactttcggcggagggacc288[1061]SequenceID64[1062]ProAlaThrValSerValSerProGlyGluArgAlaThrLeuSerCys[1063]151015[1064]ArgAlaSerGinSerlieSerPheHisLeuAlaTrpTyrGinGinLys[1065]20253054[1066]ProGlyGinAlaProSerLeuLeulieTyrGlyThrSerThrArgAla[1067]354045[1068]ThrGlylieProAlaArgPheSerGlySerGlySerGlyThrGluPhe[1069]505560[1070]ThrLeuThrlieSerSerLeuGinSerGluAspPheAlaValTyrTyr[1071]65707580[1072]CysGinGinTyrHisAsnTrpProProLeuThrPheGlyGlyGlyThr[1073]859095[1074]SequenceID65[1075]ctcgaggagtctggcccaggactggtgaagccttcggagaccctgtccctcacctgcact60[1076]gtctctggtgactccatgagtagttattattggaactggatccggcagtccccagggaag120[1077]ggactggaatggattggatatatctattacaatgggaactccaactacaacccctccctc180[1078]aggagtcgagtcaccatatcaattgacacgtccaagaagcagttctccctgaagctgacc240[1079]tctgcgaccgccgcagacacggccgtttatttctgtgcggggacggaatatgattatctt300[1080]tgggggacccccaatacggatgcatttgatatctggggccgagggacagtggtcgccgtc360[1081]tcctcagcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacc420[1082]tctgggggcacagcggccctgggctgcctggtca454[1083]SequenceID66[1084]LeuGluGluSerGlyProGlyLeuValLysProSerGluThrLeuSer[1085]151015[1086]LeuThrCysThrValSerGlyAspSerMetSerSerTyrTyrTrpAsn[1087]202530[1088]TrplieArgGinSerProGlyLysGlyLeuGluTrplieGlyTyrlie[1089]354045[1090]TyrTyrAsnGlyAsnSerAsnTyrAsnProSerLeuArgSerArgVal[1091]505560[1092]ThrlieSerlieAspThrSerLysLysGinPheSerLeuLysLeuThr[1093]65707580[1094]SerAlaThrAlaAlaAspThrAlaValTyrPheCysAlaGlyThrGlu[1095]859095[1096]TyrAspTyrLeuTrpGlyThrProAsnThrAspAlaPheAsplieTrp[1097]100105110[1098]GlyArgGlyThrValValAlaValSerSerAlaSerThrLysGlyPro[1099]115120125[1100]SerValPheProLeuAlaProSerSerLysSerThrSerGlyGlyThr[1101]130135140[1102]AlaAlaLeuGlyCysLeuVal[1103]145150[1104]SequenceID671105]1106]1107]1108]1109]1110]1111]1112]1113]1114]1115]1116]1117]1118]1119]1120]1121]1122]1123]1124]1125]1126]1127]1128]1129]ctcgaggagtctgggggaggcgtggtccagcctgggaggtccctaagactctcctgtgcagcctctggattcaccttcagtagctatggcatgcactgggtccgccaggctccaggcaaggggctggagtgggtggcagtgatatcgtatgatggaagtaataaaaagtatgcagactctgtgaagggccgattcaccatctccagagacgattccaagaaaacgctgtatctgcaaatgaacagtatgagacgtgaggacacggctgtgtatttctgtgcgaaagcggcgaatacagtaggtcgtccaggatggttcgacccctggggccagggaaccctggtcaccgtctcctcagcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctggtcaSequenceID68LeuGluGluSer1LeuSerCysTrpValSerPhe65AsnTyr50ThrArg35AspAla20GinGly5AlaGlyGlyValValSerGlyPheAlaProGlyGin10PheLys40LysThr25GlyLeuProGlyArgSerSerSerTyrGlySerAsnLys55AspSerlieSerArgAsp70GluSerMetArgArg85GlyArgProGlyTyrLysLysAspThrAlaGluTrpAlaAspSer60LeuVal45ValGly30AlaLeuArg15MetHisAlaAsnThrThrLeuVal115ValGlyArgProGlyTrp100105ThrValSerSerAlaSer120Val90PheThr75TyrPheTyrCysAlaAspProTrpValLysGlyLeuGinlieArgMet80AlaThrLysGlyPro125Gly110SerLys95GinGlyValPhe601201802403003604204451130]ProLeuAlaProSerSerLysSerThrSerGlyGlyThrAlaAlaLeu1131]1301351401132]GlyCysLeuVal1133]1451134]SequenceID691135]ctcgagtcggggggaggegegatacagccgggggagtccctgagactcttctgtgcagcc601136]tctggattcacctttcgcgactatgccatgggctgggtccgccgggctccagggaaggga1201137]ctggagtgggtctcatctatcaatgatagtggtgatagaacatattacgcagactccgtg1801138]aagggccgcttcaccatctccagagacaactccaagaattctctttatctgcaaatgacc2401139]agcctgagagccgcggacacggccatatattactgtgcgaaaggcttgatcggtctctca3001140]tcttttcatgtctggggccaagggacactggtcaccgtctcttcagcctccaccaagggc3601141]ccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctg4201142]ggctgcctggtea4331143]SequenceID70頁(yè)1144]1145]1146]1147]1148]1149]1150]1151]1152]1153]1154]1155]1156]1157]1158]1159]1160]1161]1162]1163]1164]1165]1166]1167]1168]1169]1170]1171]1172]1173]1174]1175]1176]1177]1178]1179]1180]1181]1182]Leu1PheValAspThr65SerlieValSerGluCysArgSer50lieLeuGlySerSerAlaArg35GlySerArgLeuSer115LysGlyAla20AlaAspArgAlaSer100AlaSerLysSer130SequencelD71Gly5SerProArgAspAla85SerSerThrGlyGlyGlyThrAsn70AspPheThrSerAlaPheLysTyr55SerThrHisLysGly135lieGinThrPhe25GlyLeu40TyrAlaLysAsnAlalieValTrp105GlyPro120GlyThrPro10ArgGluAspSerTyr90GlySerAlaGlyAspTrpSerLeu75TyrGinValAlaGluTyrValVal60TyrCysGlyPheLeu140SerAlaSer45LysLeuAlaThrPro125GlyLeuMet30SerGlyGinLysLeu110LeuCysArg15GlylieArgMetGly95ValAlaLeuLeuTrpAsnPheThr80LeuThrProValggggaggcttggtacagccgggggggtccctgagactatcttgtgcagcc60cctttagaaggcattccatgagttgggtccgccaggctccagggaagggg120tctcagctattagtggtagtgctggtagttcatactacgcagactccgtg180tcaccatttccagagacaatttcaagaacacattatatctgcaaatgaac240ccgaggacacggccatatattattgtgcgaaaagagtgtctgcttacctt300actcctttaactactacatagacgtctggqgcacaqggaccacggtcacc360cttccaccaagggcccatcggtcttccccctggcgccctqctccaggagc420gcacagcggccctgggctgcctggtca457SequenceIDLeuGluSer1SerValGlyThr65SerCysArgSer50lieLeuAlaGin35AlaSerArg72GlyAla20AlaGlyArgProGly5SerProSerAspGluGlyGlyGlySerAsn70AspLeuPheLysTyr55PheThrValGinThrPhe25GlyLeu40TyrAlaLysAsnAlaliePro10ArgGluAspThrTyrGlyArgTrpSerLeu75TyrGlyHislieVal60TyrCysSerSerSer45LysLeuAlaLeuMet30AlaGlyGinLysArg15SerlieArgMetArgLeuTrpSerPheAsn80Val57[1183859095[1184SerAlaTyrLeulieGlyAspTyrSerPheAsnTyrTyrlieAspVal[1185100105110[1186TrpGlyThrGlyThrThrValThrValSerSerAlaSerThrLysGly[1187115120125[1188ProSerValPheProLeuAlaProCysSerArgSerThrSerGlyGly[1189130135140[1190ThrAlaAlaLeuGlyCysLeuVal[1191145150[1192SequenceID73[1193ctcgagtcgggcccaggactggtgaagccttcacagaccctgtccctcacttgcacagtc60[1194tctggcggctccgtcagaagtggtggttactactggagctggatccgtcacctcccaggg120[1195aagggcctggagtggattgggtgcaccttttacgggggaaggacctactacagcccgtcc180[1196ctcaagagtcgagttaccatatcgacagacacgtctaagaaccagttctccctgaggctg240[1197acctctgtgactgccgcggacacggccgtgtattattgtgcgagagatgatggeggtaga300[1198cccatagacgtctggggcagagggaccacggtcgccgtctcctcagcctccaccaagggc360[1199ccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctg420[1200ggctgcctggtea433[1201SequenceID74[1202LeuGluSerGlyProGlyLeuValLysProSerGinThrLeuSerLeu[1203151015[1204ThrCysThrValSerGlyGlySerValArgSerGlyGlyTyrTyrTrp[1205202530[1206SerTrplieArgHisLeuProGlyLysGlyLeuGluTrplieGlyCys[1207354045[1208ThrPheTyrGlyGlyArgThrTyrTyrSerProSerLeuLysSerArg[1209505560[1210ValThrlieSerThrAspThrSerLysAsnGinPheSerLeuArgLeu[121165707580[1212ThrSerValThrAlaAlaAspThrAlaValTyrTyrCysAlaArgAsp[1213859095[1214AspGlyGlyArgProlieAspValTrpGlyArgGlyThrThrValAla[1215100105110[1216ValSerSerAlaSerThrLysGlyProSerValPheProLeuAlaPro[1217115120125[1218SerSerLysSerThrSerGlyGlyThrAlaAlaLeuGlyCysLeuVal[1219130135140[1220SequenceID75[1221ctcgagcagtctgggggaggcgtggtccagcccggggggtccctgagactctcctgtgca601222]gcctctggattcaccttcagtagccatggcatgaactgggtccgccaggctccagggaag1223]gggctggagtggcttgcattcataagtggtagtggtgataccatatttgacgccgactcc1224]gtgaagggccgattcaccatctccagagacaacgccgggaacttattgtatctggaaatg1225]aacagcctgcgagccgaggacacggctgtatattactgtgcaagagatcataccaggtgc1226]tattccttgagggggtgcggtatggacgtctggggccaagggaccacggtcaccgtcgcc1227]tcagcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctct1228]gggggcacagcggccctgggctgcctggtca3003604204511201802401229]SequenceID761230]LeuGluGinSerGlyGlyGlyValValGinProGlyGlySerLeuArg1231]1510151232]LeuSerCysAlaAlaSerGlyPheThrPheSerSerHisGlyMetAsn1233]2025301234]TrpValArgGinAlaProGlyLysGlyLeuGluTrpLeuAlaPhelie1235]3540451236]SerGlySerGlyAspThrliePheAspAlaAspSerValLysGlyArg1237]5055601238]PheThrlieSerArgAspAsnAlaGlyAsnLeuLeuTyrLeuGluMet1239]657075801240]AsnSerLeuArgAlaGluAspThrAlaValTyrTyrCysAlaArgAsp1241]8590951242]HisThrArgCysTyrSerLeuArgGlyCysGlyMetAspValTrpGly1243]1001051101244]GinGlyThrThrValThrValAlaSerAlaSerThrLysGlyProSer1245]1151201251246]ValPheProLeuAlaProSerSerLysSerThrSerGlyGlyThrAla1247]1301351401248]AlaLeuGlyCysLeuVal1249]1451501250]SequenceID771251]ctcgaggagtctgggggaggcgtggtccagcctgggaggtccctgagactctcctgtgca601252]gcctctggattcactttcaagaattatgccatgcactgggtccgccaggctccaggcaag1201253]gggctggagtgggtggcagttatatcatatgatgggaccaatgaatactacgcagactcc1801254]gtgaagggccgattcaccatctccagagacaattccaagaacacactgtatctgcaaatg2401255]agcagcctgagacttgaggacacgtctgtgttttactgtgcgagagacgtcccgcctaaa3001256]tcgccctgggtgccagctgccctctattggggccggggaaccctggtcaccgtctcctca3601257]gcctccaccaagggcccatcggtcttccccctggcacccctcctccaagagcacctctgg4201258]gggcacagcggccctgggctgcctggtca4491259]SequenceID781260]LeuGluGluSerGlyGlyGlyValValGinProGlyArgSerLeuArgLeuSerCysTrpValSerPhe65SerTyr50ThrArg35AspAla20Gin5AlaAlaGlyThrAsnlieSerArgSerGlyProGlySerLeuArgValProProGlyThrPheLys100ValLeu85SerAsp70GluGlu55AsnAspProTrp10PheThrPhe25LysGlyLeu40TyrTyrAlaSerLysAsnThrSerVal90AlaLysGluTrpAspAsnTyrAla30Ala15MetThr75PheSer60LeuVal45ValThrValSerLeu115LeuAlaProLeuPro130ProGlyLeuProGly145SequenceID79ctcgaggagtctggggctgagcttctggagacaccttcaaggacttgagtggatggggagttccaggmcagagtcaaaatagcagtctgagatctgacgacggaatggcttggycgtctgaagggcccatcggtcttcccgccctgggctgcctggtcaSequenceID80LeuGluGluSerLeu135ValPro105SerAlaSer120GinGluHisLeuAlaThrLysTrp140TyrTyrCysAlaLeuTyrValLysGlyLeuGinGly125GlyTrp110ProArg95GlyHislieArgMet80AspArgSerValHisSerGlyggtgaagaagcctgggtcctcacttttactatcacctggggatcagccctatccctgatacaccgcggacaaatccacgacacggccgtctattattgtggggccaagggaccacggtcacctggcaccctcctccaagacggtgaagatctcctgcaag60tgcgacaggcccctggacaa120taacaaattacgcacagaac180gaacagcctacatggaattg240cgagagagcgatcgatggcc300tcgtctcctcagcctccacc360gcacctctgggggcacagcg4204391lieSerCysTrpValSerPro50ValLys65Arg35lieLys20GinGlyAla5AlaSerAlaProAsplielieThrAlaAsp70GluValLysGlyProGlyLys10PheThr55LysAspThr25GinGlyLeu40AsnTyrProGlySerSerThrPheTrpAlaSerThrArgAsnGluGinThr75Asn60AlaMet45PheThr30GlyVal15lieArgGinAlaTyrMetGluLysThrlieArgLeu8060[1300SerSerLeuArgSerAspAspThrAlaValTyrTyrCysAlaArgGlu[1301859095[1302ArgSerMetAlaArgAlaValTrpGlyGinGlyThrThrVallieVal[1303100105110[1304SerSerAlaSerThrLysGlyProSerValPheProLeuAlaProSer[1305115120125[1306SerLysSerThrSerGlyGlyThrAlaAlaLeuGlyCysLeuVal[1307130135140[1308SequenceID81[1309ctcsagcagtctgggggaggcgtggtccagcctgagaggtccctgagactctcctgtgca60[1310gcctctggattcagtttcagtagttcttctatgcactgggtccgccaggctccaggcaag120[1311gggctggagtgggtggccgttatatcatatgatggaagcaatgaacactatgcagactcc180[1312gtgaagggccgtttcaccatctccagagacaattccaagaacacggtgtatctgcaaatg240[1313aacagcctgacacctgcggacacggctgcgtatttctgtgcgagagggggatggctccaa300[1314atacaatactactttgactactggggccaaggaaccctggtcaccgtctcctcagcctcc360[1315accaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcaca420[1316gcggccctgggctgcctggtca442[1317SequenceID82[1318LeuGluGinSerGlyGlyGlyValValGinProGluArgSerLeuArg[1319151015[1320LeuSerCysAlaAlaSerGlyPheSerPheSerSerSerSerMetHis[1321202530[1322TrpValArgGinAlaProGlyLysGlyLeuGluTrpValAlaVallie[1323354045[1324SerTyrAspGlySerAsnGluHisTyrAlaAspSerValLysGlyArg[1325505560[1326PheThrlieSerArgAspAsnSerLysAsnThrValTyrLeuGinMet[132765707580[1328AsnSerLeuThrProAlaAspThrAlaAlaTyrPheCysAlaArgGly[1329859095[1330GlyTrpLeuGinlieGinTyrTyrPheAspTyrTrpGlyGinGlyThr[1331100105110[1332LeuValThrValSerSerAlaSerThrLysGlyProSerValPhePro[1333115120125[1334LeuAlaProSerSerLysSerThrSerGlyGlyThrAlaAlaLeuGly[1335130135140[1336CysLeuVal[1337145[1338SequenceID83611339134013411342134313441345134613471348134913501351135213531354135513561357135813591360136113621363ctcgagtcgggcccaggactgctgaagccttcggagaccctgtcactcacctgcactgtctctggtggctccatcagttcctactactggacctggatccggcagaccccagggaagggactggagtggattgggtctatctctgacagtgggagcgccagctacaacccctccctcaagagtcgagtcactatatcagtggacacgtccacgaaccagttctccctgaagctgacctctgtgtccgccgcagacacggccgtatactactgtgcgagacatgtaaatatagattacgcttataacctaaattactttcactactggggccagggaaccctggtcaccgtctcctcagcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagsacctctgggggcacagcggccctgggctgcctggtcaSequenceID84LeuGluSerGly1ThrCysThrlieArgAsplie65ValSer50SerGin35GlyVal20ThrGlyLeuLeuLysGlyGlySerProGlyLysPro5SerSerAlaSerGly40Asnlie25LeuSerGluSerTyrGluTrpliePro10SerProSerLeuValAspThrTyr55ThrAsnGinPheSer70ThrAlaValTyrLys60LeuSerAlaAlaAsp85TyrAsnLeuAsnlieAspTyrAla100ThrTyr90PheSer75CysAlaThrLeuVal115TyrPheHisTyr105ValSerSerAlaSerThrLysGly120ThrLeuSerLeu15TyrTrpThrTrp30GlySerlieSer45SerArgValThrLysLeuThrSer80ArgHisValAsh95TrpGlyGinGly110ProSerValPhe125601201802403003604204451364]ProLeuAlaProSerSerLysSerThrSerGlyGlyThrAlaAlaLeu1365]1301351401366]GlyCysLeuVal1367]1451368]SequenceID851369]ctcgagtcgggcccaggactggtgaagccttcggagaccctgtccctcacttgcaatgtc601370]tctggaggctccatgaagaattacttctgggcctggatccggcagcccgcagggaaggga1201371]ctggagtggattgggtatatctattacagtgggaccaccaactacaacccctccctcaag1801372]agtcgagtcaccatatcagtggacacgtccgagaaccaattctccctgaggctgagctct2401373]gtgtccgccgcagacacggccgtctattattgtgcgagacttgtcggccccgattattgg3001374]agtggtgtcaactacttctacggaatggacgtctggggccaagggaccacggtcaccgtc3601375]tcctccgcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacc4201376]tctgggggcacagcggccctgggctgcctggtca4541377]SequenceID86621378]LeuGluSerGlyProGlyLeuVal1379]151380]ThrCysAsnValSerGlyGlySer1381]201382]lieArgGinProAlaGlyLysGly1383]35401384]TyrSerGlyThrThrAsnTyrAsn1385]50551386]lieSerValAspThrSerGluAsn1387]65701388]ValSerAlaAlaAspThrAlaVal1389]851390]ProAspTyrTrpSerGlyValAsn1391]1001392]GlyGinGlyThrThrValThrVal1393]1151201394]SerValPheProLeuAlaProSer1395]1301351396]AlaAlaLeuGlyCysLeuVal1397]1451501398]SequenceID871399]ctcgagtctgggggaggcgtggtccagcct1400]tctggattcaccttcactactcatggcatg1401]ctggagtgggtggcagttatacggtctgat1402]aagggccgattcaccatatccagagacgat1403]agcctgagagccgaggacacggctgtctac1404]cagggaaccctggtcaccgtctcctcagcc1405]gcaccctcctccaagagcacctctgggggc1406]SequenceID881407]LeuGluSerGlyGlyGlyValVal1408]151409]SerCysAlaAlaSerGlyPheThr1410]201411]ValArgGinSerProGlyLysGly1412]35401413]SerAspGlyLysThrLysTyrTyr1414]50551415]ThrlieSerArgAspAspSerLys1416]6570LysProSerGluThrLeuSerLeu1015MetLysAsnTyrPheTrpAlaTrp2530LeuGluTrplieGlyTyrlieTyr45ProSerLeuLysSerArgValThr60GinPheSerLeuArgLeuSerSer7580TyrTyrCysAlaArgLeuValGly9095TyrPheTyrGlyMetAspValTrp105110SerSerAlaSerThrLysGlyPro125SerLysSerThrSerGlyGlyThr140gggaggtccctgaaactctcctgtgcagcg60cactgggtccgccagtctccaggcaagggg120ggaaagactaaatactatgcagactccgtg180tcgaagaacacgctatatctgcaaatgaac240tactgtgcgagaaatctccaagactggggc300tccaccaagggcccatcggtcttccccctg360acagcggccctgggctgcctggtca415GinProGlyArgSerLeuLysLeu1015PheThrThrHisGlyMetHisTrp2530LeuGluTrpValAlaVallieArg45AlaAspSerValLysGlyArgPhe60AsnThrLeuTyrLeuGinMetAsn75801417]1418]1419]1420]1421]1422]1423]1424]1425]1426]1427]1428]1429]1430]1431]1432]1433]1434]1435]1436]1437]1438]1439]1440]1441]1442]1443]1444]1445]1446]1447]1448]1449]1450]1451]1452]1453]1454]1455]SerLeuArgAlaGluAsp85GinAspTrpGlyGinGly100LysGlyProSerValPhe115GlyGlyThrAlaAlaLeu130SequenceID89ctcgagtggggcgcaggactgatgagaggaccttcagtgactggagtggattggggagatagtcgagtcaccatattattgtgaccgccgcggacacggcgcccactttgactactggggggcccatcggtcttccccctctgggctgcctggtcaSequenceID90LeuGluTrpGlyThrAlaValThrProGly135LeuVal105LeuAla120CysLeuTyr90ThrProValTyrValSerCysSerSerAlaArgAsn95SerAlaSer110LysSerThr125LeuThrSergttgaagccttcggagaccctgactactggagctggatcccaataaaagtggaatatccaagacatgtccaagaggcagttgtgtattattgtgcaagaaccagggaacccaggtcaccgggcaccctcctccaagagcatgtccctcacctgcgcagtc60gccagcccccagggaagggg120cctacaacccgtccctgacg180tctccctgaggctgagctct240acgtggatcagggagatagt300tctcctcagcctccaccaag360cctctgggggcacagcggcc4204361ThrlieLyslie65ValGinThrProCysArgSer50LeuThrGlyValAlaVal20ProGin35GlyLeuAlaAspSer115SerlieAspAlaSer100SerAla5AspProSerMetAsp85AlaSer130Val145SequenceID91AlaLysSerGlyGluGlyThrSer70ThrHisSerThrLeuLeuLysArgLysTyr55LysAlaPheThrSer135ThrPhe25GlyLeu40AsnProArgGinValTyrAspTyr105LysGly120GlyGlyPro10SerGluSerPheTyr90TrpProThrSerAspTrpLeuSer75CysGlySerAlaGluAsplieThr60LeuAlaGinValAla140ThrLeuTyrGly45SerArgArgGlyTrp30GluArgLeuAsnThr110ProPhe125LeuGlySer15SerlieValSerVal95GinLeuCysLeuTrpAsnThrSer80AspValAlaLeu1456]gaggagtctgggggaggcttgggacagccg1457]tctggattcacctttagcagctatgccgtg1458]ctacagtgggtctcaactatcagtggttct1459]aggggccggtttaccgtctccagagacaat1460]agcctgagagccgaggacacggccgtttat1461]ttgcaccgctttctacaccagccttacttt1462]gtctcctcagcttccaccaagggcccatcg1463]acctctgggggcacagcggccctgggctgc1464]SequenceID921465]GluGluSerGlyGlyGlyLeuGly1466]151467]SerCysGluValSerGlyPheThr1468]201469]ValArgGinAlaProGlyLysGly1470]35401471]GlySerGlyGluAsnThrTyrTyr1472]50551473]ThrValSerArgAspAsnSerLys1474]65701475]SerLeuArgAlaGluAspThrAla1476]851477]TyrAsnAsplieLeuHisArgPhe1478]1001479]TrpGlyGinGlyThrLeuValThr1480]1151201481]ProSerValPheProLeuAlaPro1482]1301351483]ThrAlaAlaLeuGlyCysLeuVal1484]1451501485]SequenceID931486]ctcgagcagtctgggggaggcttggtcaag1487]ggctctggattcacgttcaatgactactac1488]gggctggagtggcttgcattcattagtagc1489]ctgaagggccgattcaccatctccagggac1490]aacagcctgagagtcgaggacacggccgta1491]gacgaatattacatggacgtctggggcaaa1492]accaagggcccatcggtcttccccctggca1493]gcggccctgggctgcctggtca1494]SequenceID94ggggggtccctgagactctcctgtgaagtg60acctgggtccgccaggctccagggaagggg120ggtgaaaacacatactacgcagactccgtg180tccaagaacactctgtatctacaaatgaac240ttctgtgcgagagtgccctataacgatatc300gactgctggggccagggaaccctggtcacc360gtcttccccctggcgccctgctccaggagc420ctggtca457GinProGlyGlySerLeuArgLeu1015PheSerSerTyrAlaValThrTrp2530LeuGinTrpValSerThrlieSer45AlaAspSerValArgGlyArgPhe60AsnThrLeuTyrLeuGinMetAsn7580ValTyrPheCysAlaArgValPro9095LeuHisGinProTyrPheAspCys105110ValSerSerAlaSerThrLysGly125CysSerArgSerThrSerGlyGly140cctggaggatccctgagactctcctgtgcg60ctggcttggatccgccaggctccagggaag120agtggttcttccatatactatgccgactct180aacgtccggaagtctctgtctctgcaaatg240tatttctgtgcgagagtcgttgtaccgacg300gggaccacggtcaccgtctcctcagcctcc360ccctcctccaagagcacctctgggggcaca42044265Leu1LeuTrpSerPhe65AsnValThrLeuGluSerlieSer50ThrSerValValGinSerCysArg35SerlieLeuProThr115AlaPro130LeuValAla20GinGlySerArgThr100ValGly5GlyAlaSerArgVal85AspSerSerSerGlySerProSerAsp70GluGluSerLysGlyLeuValGlyGlylie55AsnAspTyrAlaSer135PheThr25LysGly40TyrTyrValArgThrAlaTyrMet105SerThr120ThrSerLys10PheLeuAlaLysVal90AspLysGlyProAsnGluAspSer75TyrValGlyGlyGlyAspTrpSer60LeuPheTrpProThr140GlySerTyrLeu45LeuSerCysGlySer125AlaTyr30AlaLysLeuAlaLys110ValPheAlaLeuLeu15LeuPheGlyGinArg95GlyArgAlalieArgMet80ValThrProGlyCys145SequenceID951516]ctcgagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtc601517]tatggtgggtccttcagtgattactactggagctggatccgccagcccccagggaagggg1201518]ctggagtggattggggaaatcaatcatagtggacgcaccaagtacaacccgtccctcaag1801519]agtsgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctct2401520]gtgaccgccgcggacacggctgtatattactgtgcgagagtctyttccccccgtattacg3001521]atttttgaagtggtattccgctactactacatggacgtctggggcaaagggaccacggtc3601522]accgtctcctcagcttccaccaagggcccatcggtcttccccctggcgccctgctccagg4201523]agcacctctgggggcacagcggccctgggctgcctggtca460SequenceID96LeuGluTrpGly1ThrlieHislieCysArgSer50SerAlaVal20GinPro35GlyArgValAspAla5TyrProThrThrGlyGlyGlyLysSerLeuLeuLysGlyLysTyr55LysSerPhe25GlyLeu40AsnProPro10SerGluSerAsnGinPheSerAspTrpLeuSerGluTyrlieLys60LeuThrLeuTyrGly45SerTrp30GluArgLysLeuSer15SerlieValSerLeuTrpAsnThrSer661534]65701535]ValThrAlaAlaAspThrAlaVal1536]851537]ProArglieThrliePheGluVal1538]1001539]ValTrpGlyLysGlyThrThrVal1540]1151201541]GlyProSerValPheProLeuAla1542]1301351543]GlyThrAlaAlaLeuGlyCysLeu1544]1451501545]SequenceID971546]ctcgagtggggcgcggggctcttgaagcct1547]tatggtgggtccttcagtggttactactgg1548]ctggagtggattggggaaatcaatcaaagt1549]agtcgagtcaccatatcagtagacacgtct1550]gtgaccgccgcggacacggctatgtattac1551]ttggacccctggggccagggaaccctggtc1552]tcggtcttccccctggcaccctcctccaag1553]tgcctggtca1554]SequenceID981555]LeuGluTrpGlyAlaGlyLeuLeu1556]151557]ThrCysAlaValTyrGlyGlySer1558]201559]lieArgGinSerProGlyLysGly1560]35401561]GinSerGlySerThrHisTyrAsn1562]50551563]lieSerValAspThrSerLysAsn1564]65701565]ValThrAlaAlaAspThrAlaMet1566]851567]MetGlyGlyTrpLeuAspProTrp1568]1001569]SerSerAlaSerThrLysGlyPro1570]1151201571]SerLysSerThrSerGlyGlyThr1572]1301357580TyrTyrCysAlaArgValSerSer9095ValPheArgTyrTyrTyrMetAsp105110ThrValSerSerAlaSerThrLys125ProCysSerArgSerThrSerGly140Valtcggagaccctgtccctcacctgcgctgtc60acctggatccgccagtccccagggaagggg120ggaagcacccactacaacccgtcgttgaac180aagaaccagatcttcctgaacgtgaactct240tgtgcgagatactcgaatatgggtggctgg300atcgtctcctcagcctccaccaagggccca360agcacctctgggggcacagcggccctgggc420430LysProSerGluThrLeuSerLeu1015PheSerGlyTyrTyrTrpThrTrp2530LeuGluTrplieGlyGlulieAsn45ProSerLeuAsnSerArgValThr60GinliePheLeuAsnValAsnSer7580TyrTyrCysAlaArgTyrSerAsn9095GlyGinGlyThrLeuVallieVal105110SerValPheProLeuAlaProSer125AlaAlaLeuGlyCysLeuVal1401573]SequenceID991574]ctcgagtctgggggaggcctggtcaagcctggggggtccctgagactctcctgtgcagcc601575]tctggcttcagcttcagtgattatactatgaactgggtccgccaggctccagggaggggg1201576]ctggagtgggtctcatcaataagaagcactagtccttacatattctacgcagactcagtg1801577]aagggccgattcaccatctccagagacaacgccgcaaactcactgtatctgcaaatgaac2401578]agcctgcgagccgaggacacggctgtctattactgtgcgagcgcccgccctgttagtatg3001579]attcggggagttcccccccgctacaattaccacggtatggacgtctggggcctggggacc3601580]acggtcaccgtctcctcagcctccaccaagggcccatcggtcttccccctggcaccctcc4201581]tccaagagcacctctgggggcacagcggccctgggctgcctggtca4661582]SequenceID1001583]LeuGluSerGlyGlyGlyLeuValLysProGlyGlySerLeuArgLeu1584]1510151585]SerCysAlaAlaSerGlyPheSerPheSerAspTyrThrMetAsnTrp15861587158815891590159115921593159415951596159715981599160020ValArgGinAla35SerProSerThr50lieTyrSerArgAsp25ProGlyArgGlyLeu40TyrThr65SerLeuArgAlaProValSerMet100TrpGlu85lieArgliePhe55AsnAla70AspAlaAlaAsnThrAlaValGluTrpValAspSerSerMetAspVal115GlyProSerValGlyValGlyLeuGlyThrLys130Phe135Thr120Pro1601]SerGlyGlyThrAlaAlaLeuGly1602]1451501603]SequenceID1011604]ctcgagtctgggggaggcctggtcaagcct1605]tctggcttcagcttcagtgattatactatg1606]ctggagtgggtctcatcaataagaagcact1607]aagggccgattcaccatctccagagacaat1608]agcctgcgagccgaggacacggctgtctat1609]attcggggagttcccccccgctacaattac1610]acggtcaccgtctcctcagcctccaccaag1611]tccaagagcacctctgggggcacagcggccPro105ThrLeuCysTyr90ProValAlaLeuLeu75TyrArgThrProVal155Val60TyrCysTyrValSer140Ser45LysLeuAlaAsnSer125Ser30SerGlyGinSerTyr110SerlieArgArgPheMetAla95HisAlaLysSerAsn80ArgGlySerThrggggggtcccaactgggtccagtccttacagccgcaaacttactgtgcgacacggtatggggcccatcggctgggctgcctgagactctcctgtgcagcc60gccaggctccagggaggggg120tattctacgcagactcagtg180cactgtatctgcaaatgaac240gcgcccgccctgttagtatg300acgtctggggcctggggacc360tcttccccctggcaccctcc420tggtca466681612]SequenceID1021613]LeuGluSerGlyGlyGlyLeuVal1614]151615]SerCysAlaAlaSerGlyPheSer1616]201617]ValArgGinAlaProGlyArgGly1618]35401619]SerThrSerProTyrliePheTyr1620]50551621]ThrlieSerArgAspAsnAlaAla1622]65701623]SerLeuArgAlaGluAspThrAla1624]851625]ProValSerMetlieArgGlyVal1626]1001627]MetAspValTrpGlyLeuGlyThr1628]1151201629]ThrLysGlyProSerValPhePro1630]1301351631]SerGlyGlyThrAlaAlaLeuGly1632]1451501633]SequenceID1031634]ctcgagcagtctgggggaggcttggtaaac1635]gcctctggattcactttcagtaaggcctgg1636]gggctggagtgggttggccgtattaaaagc1637]gcacccgtgaaaggccgattctccatctcc1638]caaatgagcagcctgaaaaccgaggacaca1639]gcacacccggatgcttttgatatctggggc1640]tccaccaagggcccatcggtcttccccctg1641]acagcggccctgggctgcctggtca1642]SequenceID1041643]LeuGluGinSerGlyGlyGlyLeu1644]151645]LeuSerCysAlaAlaSerGlyPhe1646]201647]TrpValArgGinAlaProGlyLys1648]35401649]LysSerMetThrAspSerGlyThr1650]5055LysProGlyGlySerLeuArgLeu1015PheSerAspTyrThrMetAsnTrp2530LeuGluTrpValSerSerlieArg45AlaAspSerValLysGlyArgPhe60AsnSerLeuTyrLeuGinMetAsn7580ValTyrTyrCysAlaSerAlaArg9095ProProArgTyrAsnTyrHisGly105110ThrValThrValSerSerAlaSer125LeuAlaProSerSerLysSerThr140CysLeuVal155cctggggggtcccttagactctcctgtgca60atgacctgggtccgccaggctccagggaag120atgactgatagtgggacaacagactacgct180agagacgattC￡l￡l￡l￡l￡l￡lC￡ltgctgtatttg240gccgtgtattactgtgccacagatccaagg300caagggacaatggtcaccgtctcttcagcc360gcaccctcctccaagagcacctctgggggc420445ValAsnProGlyGlySerLeuArg1015ThrPheSerLysAlaTrpMetThr2530GlyLeuGluTrpValGlyArglie45ThrAspTyrAlaAlaProValLys60Gly65GinThrThrProArgMetAspMetPheSerProVal115AlaSerlieSerLeu130CysLeuArg100ThrProValLeu85AlaValSerSer70LysHisSerSerArgThrProSerLys135AspAspSerGluAspAspAla105AlaSer120SerThrThr90PheThrSerLys75AlaAspLysGlyAsnVallieGlyGly140MetTyrTrpPro125ThrLeuTyrTyrGly110SerCys95GinValAlaAlaLeu80AlaGlyPheLeuGly145SequenceID105ctcgagtcggggggaggctttctggattcaccttcagtaactggaatatgtttcagctataacggcagattcaccatctcagcctgagagctgaggacattctaaaatggacgtctggggggcccatcggtcttccccctctgggctgcctggtcaSequenceID106LeuGluSerGlyggtccagcctggggggtcccttatgctatacattgggtcctagtagcaatggggatagcacagagaccattccaagaacaggctgtgtattactgtgtgaccaagggaccacggtcaccgggcaccctcctccaagagcatgagactctcctgtgcagcc60gccaggctccagggaaggga120catattatgcaaagtctgtg180cgctgtatcttcagatgggc240ggtcccccctcctacgatat300tctcctcagcctccaccaag360cctctgggggcacagcggcc4204361SerValSerThr65SerLeuThrProCysArgAsn50lieLeuLeuValSerAlaAla20AlaGin35GlySerArgArgSer115SerAspArgAlaTyr100SerGly5SerProSerAspGlu85SerAlaLysSerGlyGlyGlyThrHis70AspLysSerThrLeuValGinPheLysTyr55SerMetMetThrSerThrPhe25GlyLeu40TyrAlaLysAsnAlaValAspVal105LysGly120GlyGlyPro10SerGluLysThrTyr90TrpProThrGlyAsnTyrSerLeu75TyrGlySerAlaGlyTyrValVal60TyrCysGinValAlaSerLeuAlaSer45AsnLeuValGlylie30AlaGlyGinArgThr110ProPhe125LeuGlyArg15HislieArgMetSer95ThrLeuCysLeuTrpSerPheGly80ProValAlaLeu70[1690]130135140[1691]Val[1692]145[1693]SequenceID107[1694]tctccttccaccctgtctgcatctgtcggcgacagagtcaccatcacttgccgggccagt60[1695]caaagtattagaacctggttggcctggtatcagcagaaaccagggaaagcccctaacctc120[1696]ctgatctatcatgcctccagtttggaaagtggggtcccatcaaggttcagcggtaatgga180[1697]tctgggacggaattcactctcaccatcaacagcctgcagcctgatgattttgcaacttat240[1698]tactgccaacactatattacttattcgtggacgttcggccaagggaccaaggtggaaatc300[1699]aaacgaactgtggctgcacc320[1700]SequenceID108[1701]SerProSerThrLeuSerAlaSerValGlyAspArgValThrlieThr[1702]151015[1703]CysArgAlaSerGinSerlieArgThrTrpLeuAlaTrpTyrGinGin[1704]202530[1705]LysProGlyLysAlaProAsnLeuLeulieTyrHisAlaSerSerLeu[1706]354045[1707]GluSerGlyValProSerArgPheSerGlyAsnGlySerGlyThrGlu[1708]505560[1709]PheThrLeuThrlieAsnSerLeuGinProAspAspPheAlaThrTyr[1710]65707580[1711]TyrCysGinHisTyrlieThrTyrSerTrpThrPheGlyGinGlyThr[1712]859095[1713]LysValGlulieLysArgThrValAlaAla[1714]100105[1715]SequenceID109[1716]tctccttccaccctgtctgcatctgtaggagacagagtcaccgtcacttgccgggccagt60[1717]cagagtattagtagctggttggcctggtatcagcagaaaccagggaaagcccctaaactc120[1718]ctgatctatgatgcctccagtttgcaaagtggggtcccatcaaggttcagcggcggtgga180[1719]tctgggacagaattcactctcaccatcaacagcctgcagcctgatgattttgcaacttat240[1720]tactgccaacagtataatagttatccgtggacgttcggccaagggaccaaggtggaaatc300[1721]aaacgaactgtggctgcacc320[1722]SequenceID110[1723]SerProSerThrLeuSerAlaSerValGlyAspArgValThrValThr[1724]151015[1725]CysArgAlaSerGinSerlieSerSerTrpLeuAlaTrpTyrGinGin[1726]202530[1727]LysProGlyLysAlaProLysLeuLeulieTyrAspAlaSerSerLeu[1728]3540451729]GinSerGlyValProSerArgPheSerGlyGlyGlySerGlyThrGlu1730]5055601731]PheThrLeuThrlieAsnSerLeuGinProAspAspPheAlaThrTyr1732]657075801733]TyrCysGinGinTyrAsnSerTyrProTrpThrPheGlyGinGlyThr1734]8590951735]LysValGlulieLysArgThrValAlaAla1736]1001051737]Sequence！ID1111738]tctccttccaccctgtctgc:atctgtaggagacaaagtcaccatcacttgccgggccagt601739]cagagtattagtaggtgggtggcctggtatcagcagaaaccagggacagcccctaaggtc1201740]ctgatctatgatgcctccag；gttggaaagtggggtcccatcaaggttcagcggcagtgga1801741]tctgggacagaattcactct,caccatcagtagcctgcagcctgatgattttgcaacttat2401742]tactgccaacagtataatag；ttatttgtggacgttcggccaagggaccaaggtggaaatc3001743]aaacgaactgtggctgcacc3201744]Sequence！ID1121745]SerProSerThrLeuSerAlaSerValGlyAspLysValThrlieThr1746]1510151747]CysArgAlaSerGinSerlieSerArgTrpValAlaTrpTyrGinGin1748]2025301749]LysProGlyThrAlaProLysValLeulieTyrAspAlaSerArgLeu1750]3540451751]GluSerGlyValProSerArgPheSerGlySerGlySerGlyThrGlu1752]5055601753]PheThrLeuThrlieSerSerLeuGinProAspAspPheAlaThrTyr1754]657075801755]TyrCysGinGinTyrAsnSerTyrLeuTrpThrPheGlyGinGlyThr1756]8590951757]LysValGlulieLysArgThrValAlaAla1758]1001051759]Sequence！ID1131760]tctccaccctccctgtctgc:atttgttggagacaaagtcaccatcacttgccgggcaagt601761]caggacatttacagagcttt,agcctggtatcagcagaagccagggaagcctcctaacctc1201762]ttgatctatcatgcctccag；tttgcaaagaggggtcccatcaaggttcagcggcagtgga1801763]tctgggacagatttcactct,caccatcagcagcctgcagcctgaagattttgcaacttat2401764]tactgtcaacagtttaatag；ttttccgctcactttcggcggacggaccaacgtggagatc3001765]aaccgaactgtggctgcacc3201766]Sequence！ID1141767]SerProProSerLeuSerAlaPheValGlyAspLysValThrlieThr1768]1510151769]CysArgAlaSerGinAsplieTyrArgAlaLeuAlaTrpTyrGinGin1770]2025301771]LysProGlyLysProProAsnLeuLeulieTyrHisAlaSerSerLeu1772]3540451773]GinArgGlyValProSerArgPheSerGlySerGlySerGlyThrAsp1774]5055601775]PheThrLeuThrlieSerSerLeuGinProGluAspPheAlaThrTyr1776]657075801777]TyrCysGinGinPheAsnSerPheProLeuThrPheGlyGlyArgThr1778]8590951779]AsnValGlulieAsnArgThrValAlaAla1780]1001051781]SequenceID1151782]tctccatcctccctgtctgcatctgtaggagacagaatcaccatcacttgccgggccagt601783]caagacattagtagttattt:agggtggtatcagcagaaaccagggacggcccctaagctc1201784]ctgatatatgctgcatccac:tttgcacagtggggtcccatcaaggttcagcggcagtgga1801785]tctgggacagaattcactctaggctgcagcctgaagactttgcagcttat2401786]tactgtcaacaggttgacagttatcctcgaactttcggcggagggaccaaggtggagatg3001787]aaacgaactgtggctgcacc3201788]SequenceID1161789]SerProSerSerLeuSerAlaSerValGlyAspArglieThrlieThr1790]1510151791]CysArgAlaSerGinAsplieSerSerTyrLeuGlyTrpTyrGinGin1792]2025301793]LysProGlyThrAlaProLysLeuLeulieTyrAlaAlaSerThrLeu1794]3540451795]HisSerGlyValProSerArgPheSerGlySerGlySerGlyThrGlu1796]5055601797]PheThrLeuThrlieAsnArgLeuGinProGluAspPheAlaAlaTyr1798]657075801799]TyrCysGinGinValAspSerTyrProArgThrPheGlyGlyGlyThr1800]8590951801]LysValGluMetLysArgThrValAlaAla1802]1001051803]SequenceID1171804]tctccatccatcctgtctgcatctgtaggagacagagtcaccatcacttgccgggccagt601805]caagacattagtagttattt:agggtggtatcagcagaaaccagggacggcccctaagctc1201806]ctgatatatgctgcatccac:tttgcacagtggggtcccatcaaggttcagcggcagtgga180180718081809181018111812181318141815181618171818181918201821182218231824182518321833183418351836183718381839184018411842184318441845tctgggacagaattcactctcacaatcaataggctgcagcctgaagactttgcagcttattactgtcaacaggttgacagttatcctcgaactttcggcggagggaccaaggtggagatgaaacgaactgtggctgcaccSequenceIDSerProSer1CysLysHisPhe65TyrArgAlaProSer50ThrCysValGly35GlyLeuGinGluLysSequenceID118lieSer20ThrValThrGinMet100119Leu5GinAlaProlieSerAspProSerAsn70AspAlaSerVallieLysVal85LysArgArg55ArgSerThrSerSer25LeuLeu40PheSerLeuGinTyrProValAla105Gly10TyrlieGlyProArg90AlaAspLeuTyrSerArgGlyAlaGly60AspValThrTrpGlu75ThrPheAla45SerPheGlyTyr30SerGlyAlaGlylie15GinThrThrAlaGly95ThrGinLeuGluTyr80ThrSequenceIDSerProAla1CysLysGinPhe65TyrArgAlaGinThr50ThrCysLysValGly35GlyLeuLeuGlu120SerSer20GlyValThrGinlieLeu5GinAlaProlieTyrGlyProProSer70AsnAlaSerVallieLysHis85LysArgArg55SerSerThrArgLys25CysLeu40PheSerLeuGinTyrProValAlaGly10AlaLeuGlyProTrp90AlaAspLeuTyrSerThrGlyAlaGly60AspValThrTrpGlu75ThrPheAla45SerPheGlyTyr30PheGlyAlaGinlie15GinThrThrThrGly95ThrGinLeuGluTyr80Thr2403003201826]tctccagcctccctatatgcgtctgttggcgacaccgtcaccatcacttgccgggcaagt601827]cagggcattagaaaagctttaggctggtatcagcagaaacaagggggagcccctaagtgc1201828]ctgctctatgctgcattcactttgcaaactggagtcccaccaaggttcagcggcagtgga1801829]tctgggacagaattcactctcacaatcagtagcctgcagcctgaagactttgcaacttat2401830]tactgtctacagcataattcttatccttggacgttcggccaagggaccaaggtggaaatc3001831]aaacgaactgtggctgcacc320741846]1001847]SequenceID1211848]tctccatcctccctgtctgcatctgtagga1849]cagagaattagtacctatgtaaattggtat1850]ctgatctatgccgcatccagtttgcaaagt1851]tctgggacagatttcactctcaccatcagc1852]tactgtcaacagagttacatatcttggacg1853]cgaactgtggctgcacc1854]SequenceID1221855]SerProSerSerLeuSerAlaSer1856]151857]CysArgAlaSerGinArglieSer1858]201859]LysProGlyLysGlyProLysLeu1860]35401861]GinSerGlyValProSerArgPhe1862]50551863]PheThrLeuThrlieSerSerLeu1864]65701865]TyrCysGinGinSerTyrlieSer1866]851867]ValGlulieLysArgThrValAla1868]1001869]SequenceID1231870]tctccatcctccctgtctgcatctgtagga1871]cagagcgttacgagatatttaaattggtat1872]ctgatctatgctgcatccagtttgcaaagt1873]tctgggacagatttcactctcaccatcagc1874]tactgtcaacagagttacagtaccccttgg1875]aaacgaactgtggctgcacc1876]SequenceID1241877]SerProSerSerLeuSerAlaSer1878]151879]CysArgAlaSerGinSerValThr1880]201881]LysProGlyLysAlaProLysVal1882]35401883]GinSerGlyValProSerArgPhe1884]5055105gacagaatcaccatcacttgccgggcaagt60cagcagaagccagggaaaggccctaagctc120ggggtcccatcaaggttcagtggcagtgga180agtctccagtctgaagactttgcaacttac240ttcggccaagggaccaaggtggaaatcaaa300317ValGlyAspArglieThrlieThr1015ThrTyrValAsnTrpTyrGinGin2530LeulieTyrAlaAlaSerSerLeu45SerGlySerGlySerGlyThrAsp60GinSerGluAspPheAlaThrTyr7580TrpThrPheGlyGinGlyThrLys9095Ala105gacagagtcaccatcacttgccgggcaagt60cagcagaaaccaggcaaagcccctaaggtc120ggggtcccatcaaggttcagtggcagtgga180agtctgcaacctgaagattttgcatcttac240acgttcggccaagggaccaaggtggaaatc300320ValGlyAspArgValThrlieThr1015ArgTyrLeuAsnTrpTyrGinGin2530LeulieTyrAlaAlaSerSerLeu45SerGlySerGlySerGlyThrAsp60[1885PheThrLeuThrlieSerSerLeuGinProGluAspPheAlaSerTyr[188665707580[1887TyrCysGinGinSerTyrSerThrProTrpThrPheGlyGinGlyThr[1888859095[1889LysValGlulieLysArgThrValAlaAla[1890100105[1891SequenceID125[1892tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaagt60[1893cagagcattagcagctatttaaattggtatcaacagaaaccagggaaagcccctaagctc120[1894ctgataaatgttgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtgca180[1895tctgggacaaatttcactctcaccatcagcagtctgcaacctgaagattttgcaacttac240[1896tactgtcagcagacttacaggagccctaggacgttcggccaagggaccaaggtggaaatc300[1897aaacgaactgtggctgcacc320[1898SequenceID126[1899SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr[1900151015[1901CysArgAlaSerGinSerlieSerSerTyrLeuAsnTrpTyrGinGin[1902202530[1903LysProGlyLysAlaProLysLeuLeulieAsnValAlaSerSerLeu[1904354045[1905GinSerGlyValProSerArgPheSerGlySerAlaSerGlyThrAsn[1906505560[1907PheThrLeuThrlieSerSerLeuGinProGluAspPheAlaThrTyr[190865707580[1909TyrCysGinGinThrTyrArgSerProArgThrPheGlyGinGlyThr[1910859095[1911LysValGlulieLysArgThrValAlaAla[1912100105[1913SequenceID127[1914tctccatcctccctgtctgcatctgtaggagacagagtcaccatcagttgccgggcaagt60[1915cagagcattagcgactatttacattggtatcagcagaaaccagggaaagcccctaacctc120[1916ctgatctatgctgcatccaatttgcacagtggggtcccatcgaggttcagtggcagtgga180[1917tctgggacagatttcactctcaccatcaacagtctgcaacctgaagattttgcaacttac240[1918tactgtcaacagagtttctctaccccgtggacgttcggccacgggaccaaggtggaaatc300[1919aaacgaactgtggctgcacc320[1920SequenceID128[1921SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieSer[1922151015[1923CysArgAlaSerGinSerlieSerAspTyrLeuHisTrpTyrGinGin761924]201925]LysProGlyLysAlaProAsnLeu1926]35401927]HisSerGlyValProSerArgPhe1928]50551929]PheThrLeuThrlieAsnSerLeu1930]65701931]TyrCysGinGinSerPheSerThr1932]851933]LysValGlulieLysArgThrVal1934]1001935]SequenceID1291936]tctccatcctccctgtctgc:atctgttgga1937]cagagcatcagcaactattt,aaattggtat1938]ctgatctctggtgcatccag；tttgcagagt1939]tttgggacagatttcagtctCclCCcltCclclC1940]tactgtcaacagggttacag；caccccgtac1941]aaacgaactgtggctgcacc1942]SequenceID1301943]SerProSerSerLeuSerAlaSer1944]151945]CysArgAlaSerGinSerlieSer1946]201947]LysProGlyLysAlaProLysLeu1948]35401949]GinSerGlyValProSerArgPhe1950]50551951]PheSerLeuThrlieAsnPheLeu1952]65701953]TyrCysGinGinGlyTyrSerThr1954]851955]LysLeuGluMetLysArgThrVal1956]1001957]SequenceID1311958]tctccatcctccctggctgc:atctgtcgga1959]cagagcatttccaactatgt,aaattggtat1960]ctaatctctgctgcatccaa,tttacaaagt1961]tctgggacagatttcactct,caccatcagt1962]tactgtcaacagagtcaggctgcccctctc2530LeulieTyrAlaAlaSerAsnLeu45SerGlySerGlySerGlyThrAsp60GinProGluAspPheAlaThrTyr7580ProTrpThrPheGlyHisGlyThr9095AlaAla105gacagagtcaccatcacttgccgggcaagt60cagcagaaaccagggaaagcccctaaactc120ggggtcccatctaggttcagtggcagtgga180tttctgcaatctgaagattttgctgtttac240acttttggccaggggaccaagctggagatg300320ValGlyAspArgValThrlieThr1015AsnTyrLeuAsnTrpTyrGinGin2530LeulieSerGlyAlaSerSerLeu45SerGlySerGlyPheGlyThrAsp60GinSerGluAspPheAlaValTyr7580ProTyrThrPheGlyGinGlyThr9095AlaAla105aacagagtcgccatcacttgccgggcaagt60cagcagaaaccagggaaagcccctaacctc120ggggtcccatcaaggttcactggcagtgga180agtctggaacctgaagattttgcaacttac240actttcggcggagggaccaaggtggagatc30077[1963aagcgaactgtggctgcacc320[1964SequenceID132[1965SerProSerSerLeuAlaAlaSerValGlyAsnArgValAlalieThr[1966151015[1967CysArgAlaSerGinSerlieSerAsnTyrValAsnTrpTyrGinGin[1968202530[1969LysProGlyLysAlaProAsnLeuLeulieSerAlaAlaSerAsnLeu[1970354045[1971GinSerGlyValProSerArgPheThrGlySerGlySerGlyThrAsp[1972505560[1973PheThrLeuThrlieSerSerLeuGluProGluAspPheAlaThrTyr[197465707580[1975TyrCysGinGinSerGinAlaAlaProLeuThrPheGlyGlyGlyThr[1976859095[1977LysValGlulieLysArgThrValAlaAla[1978100105[1979SequenceID133[1980tctccatcctccctggctgcatctgtcggagacagagtcgccatcacttgccgggcaagt60[1981cagagcatttccaactatgtaaattggtatcagcagaaaccagggaaagcccctaacctc120[1982ctaatctctgctgcatccaatttacaaagtggggtcccatcaaggttcactggcagtgga180[1983tctgggacagatttcactctcaccatcagtagtctggaacctgaagattttgcaacttac240[1984tactgtcaacagagtcaggctgcccctctcactttcggcggagggaccaaggtggagatc300[1985aagcgaactgtggctgcacc320[1986SequenceID134[1987SerProSerSerLeuAlaAlaSerValGlyAspArgValAlalieThr[1988151015[1989CysArgAlaSerGinSerlieSerAsnTyrValAsnTrpTyrGinGin[1990202530[1991LysProGlyLysAlaProAsnLeuLeulieSerAlaAlaSerAsnLeu[1992354045[1993GinSerGlyValProSerArgPheThrGlySerGlySerGlyThrAsp[1994505560[1995PheThrLeuThrlieSerSerLeuGluProGluAspPheAlaThrTyr[199665707580[1997TyrCysGinGinSerGinAlaAlaProLeuThrPheGlyGlyGlyThr[1998859095[1999LysValGlulieLysArgThrValAlaAla[2000100105[2001SequenceID135[2002]tctccatcctccctgggcgcatctgtaggg[2003]cagatcattaccacccatttaaattggtat[2004]ctgatctatggtgcatccaatttgcaagct[2005]tctgggactgatttcactctcaccatcagc[2006]tactgtcaccagacttacacgacccctctc[2007]aaacgaactgtggctgcacc[2008]SequenceID136[2009]SerProSerSerLeuGlyAlaSer[2010]15[2011]CysArgAlaSerGinlielieThr[2012]20[2013]LysProGlyLysAlaProAsnLeu[2014]3540[2015]GinAlaGlyValProSerArgPhe[2016]5055[2017]PheThrLeuThrlieSerSerLeu[2018]6570[2019]TyrCysHisGinThrTyrThrThr[2020]85[2021]LysValAsplieLysArgThrVal[2022]100[2023]SequenceID137[2024]tctccttcctccctgtctgcatctgtcgga[2025]cagaccattaccagggccttaaactggtac[2026]ctgatctttggtgcatccagcttgcaaagg[2027]tctgagacagatttcactctcaccatcagc[2028]tactgtcagcagactcagactagtcctcgc[2029]ataaagcgaactgtggctgcacc[2030]SequenceID138[2031]SerProSerSerLeuSerAlaSer[2032]15[2033]CysArgAlaSerGinThrlieThr[2034]20[2035]ThrProGlyLysGlyProLysLeu[2036]3540[2037]GinArgGlyValSerSerArgPhe[2038]5055[2039]PheThrLeuThrlieSerGlyLeu[2040]6570gacatcgtcaccatcacttgccgggcaagt60cagcaaaaaccaggcaaagcccctaacctc120ggggtcccatcgaggttcagtggcagtgga180agtctgcaaccagaagattttgcaacttac240actttcggcggagggaccaaggtggacatc300320ValGlyAsplieValThrlieThr1015ThrHisLeuAsnTrpTyrGinGin2530LeulieTyrGlyAlaSerAsnLeu45SerGlySerGlySerGlyThrAsp60GinProGluAspPheAlaThrTyr7580ProLeuThrPheGlyGlyGlyThr9095AlaAla105gacagagtcaccatctcttgccgggcaagt60CclclCclCclCclCctgggaaaggccctaaactc120ggggtctcatcgaggttcagtggcagtggc180ggtctgcagcctgaagattttgcgacttac240tacacctttggccaagggaccaagctggag300323ValGlyAspArgValThrlieSer1015ArgAlaLeuAsnTrpTyrGinHis2530LeuliePheGlyAlaSerSerLeu45SerGlySerGlySerGluThrAsp60GinProGluAspPheAlaThrTyr758079TyrCysGinGinThrGinThrSerProArgTyrThrPheGlyGinGly859095ThrLysLeuGlulieLysArgThrValAlaAla100105SequenceID139tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggccagtcagggcattgacaattatttagcctggtatcagcaaagaccagggaaagcccctaagctcctgatctatggtgcatccactttgcaaagtggggtcccatcaaggttcagcggcagtggatctgggacagtcttcactctcaccatcagcagcctgcagcctgaagattttgcaacttattactgtcaacagcttaatagttatccttcgatcaacttcggccaagggacacgactggagattaaacgaactgtggctgcaccSequenceIDSerProSer1CysArgGinPhe65TyrArgAlaProSer50ThrCysThrArgGly35GlyLeuGinLeu140SerSer20LysValThrGinLeu5GinAlaProlieLeu85lieSerGlyProSerSer70AsnAlaSerVallieLysArg55SerAspAsn25LeuLeu40PheSerSerLysArgLeuGinTyrProGly10TyrlieGlyProAspLeuTyrSerArgAlaGlyGly60AspValThrTrpSer90AlaAlaGlu75lieAsnAla45SerPhePheTyr30SerGlyAlaGlylie15GinThrThrThrGin95ThrGinLeuValTyr80GlyGlulieLysArgThrVal100105SequenceID141tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccaggcgagtcaggacattagttactatttaaattggtatcagcagaaaccagggaaagcccctaagctcctgatctacgatgcattgaatgtggaaacaggggtcccatcaaggttcggtggaagtggatctgggacagatttcactttcaccatcagcagcctgcagcctggagattttgcaatatattactgtcagcagtatgctaatttcccgtatacttttggccaggggaccaagctggagatcaaacgaactgtggctgcaccSequenceID142SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr151015CysGinAlaSerGinAsplieSerTyrTyrLeuAsnTrpTyrGinGin202530LysProGlyLysAlaProLysLeuLeulieTyrAspAlaLeuAsnVal60120180240300323601201802403003202080]2081]2082]2083]2084]2085]2086]2087]2088]2089]2090]2091]2092]2093]2094]2095]2096]2097]2098]2099]2100]2101]2102]2103]2104]2105]2106]2107]2108]2109]2110]2111]2112]2113]2114]2115]2116]2117]2118]GluThr50Thr35GlyValProSerPheThrliePhe65TyrCysGinGinArg55SerSer70AlaAsnPhePro40PheGlyGlySerLeuGinProTyr85LysArgThrValLysLeuGlulie100SequenceID143tctccatcctccctgtctgtatctgtaggacacgacattagcaactatttacattggtttctgatctacgatgcatccaatttggaaacatttgggacagattttactttcaccatcagctactgtcaacagtatggtaatctcccgtacaaacgaactgtggctgcaccSequenceID144Ala105Tyr90AlaGly75ThrGly60Asp45SerPhePheGlyGlyAlaGinThrAsplieGly95Tyr80ThrgacagagtcaccatcacttgccaggcgagtcagcagaaaccaggggaagcccctaagctcggggtcccatcaaggttcaggggaagtggaagcctgcagcctgaagatattgcaacatatacttttggccaggggaccaagctgcagatcSerProSerSer1CysGinAlaLeuSerValSerVal5HisAsplieSerLysProGluThr50ThrGly35GlyPheThrliePhe65TyrCysGinGinSerHisAsplieSerAsn2025GluAlaProLysLeuLeu40ValProSerArgPheArg55SerLeuGinGlyAspArg10TyrLeuHisValThrTrpSer70GlyAsnLeuProlieTyrAspGlySerProTyr85LysArgThrValLysLeuGinlie100SequenceID145tctccatcctccctgtccgcatctataggagagggcattagcaactatttaaattggtatctaatctacgatgcatccaatttggaatcacttgagacagattttactctcaccatcaactactgtcaacagtatgatagtctccctctcaaacgaactgtggctgcaccSequenceID146Ala105Tyr90AlaGlu75ThrGly60AspAla45PheliePheGlyPhe30SerGlyAlaGinlie15GinThrGinAsnLeuThrAspThrGly95Tyr80Thrgacagagtcagtatcgcttgccaggcgagtcagcagaaaccagggaaagcccctaagctcggggtcccatcaagatttagtggaagtggcagcctgcagcctgaagatattgcaacatatactttcggcggagggaccaaggtggagatc601201802403003206012018024030032081[21]9]SerProSerSerLeuSerAlaSerIleGlyAspArgValSerIleAla[2120]l5lo15[2121]CysGlnAlaSerGhGlyIleSerAsh／yrLeuAsh／rp／yrGlnGln[21221202530[2123]LysProGlyLysAlaProLysLeuLeuIle／yrAspAlaSerAshLeu[2124]354045[2125]GhSerGlyValProSerArgPheSer61ySer61yLeuGh／hrAsp[2126]505560[2127]Phe／hrLeu／hrIleAshSetLeuGlnPro61uAspIleAlaThrTyr[2128]65707580[2129]／yrCysGlnGln／yrAspSetLeuProLeu／hrPhe61y61y61y／hr[2130]859095[213]]LysValGhIleLysArg／hrValAlaAla[21321100105[2133]Sequence工D147[2134]tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccaggcgagt60[2135]caggacattagcaactatttaaattggtatCaaCagaaaCcagggaaagcccctaagctc120[2136]ctgatctacgatgcatccaatttgcaagcaggggtcccgtcaaggttcagtggaagtgga180[2137]tctgggacagattttactttcaccatcagcagcctgcagcctgaagatattgcaacatat240[2138]tactgtcaacagtatgataatctccctcccactttcggcggagggaccaaggtggagttc300[2139]aaacgaactgtggctgcacc320[2140]Sequence工D148[214]]SerProSerSerLeuSerAlaSerValGlyAspArgVal／hrIle／hr[21421l5lo15[2143]CysGlnAlaSetGlnAspIleSetAsh／yrLeuAsh／rp／yrGlnGln[2144]202530[2145]LysProGlyLysAlaProLysLeuLeuIle／yrAspAlaSetAshLeu[2146]354045[2147]GlnAlaGlyValProSetArgPheSet61ySet61ySet61y／hrAsp[2148]505560[2149]Phe／hrPhe／hrIleSerSerLeuGlnPro61uAspIleAlaThrTyr[2150]65707580[215]]／yrCysGlnGln／yrAspAshLeuProPro／hrPhe61y61y61y／hr[21521859095[2153]LysValGhPheLysArg／hrValAlaAla[2154]100105[2155]Sequence工D149[2156]tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgtcgggcgagt60[2157]cagggcattaataattatttagcctggtatcagcagaaaccagggaaagttccgcagctc120[2158]ctgatcgatgctgcatccactttgcaatcaggggtcccatctcggttcagtggcagtgga180[2159]tctgggacagatttcactctcaccatcagcagcctgcagcctgaagatgttgcaacttat240[2160]tactgtcaaaagtataacagtgccccattcactttcggccctgggaccaaagtggatatc300[2161]aaacgaactgtggctgcacc320[2162]SequenceID150[2163]SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr[2164]151015[2165]CysArgAlaSerGinGlylieAsnAsnTyrLeuAlaTrpTyrGinGin[2166]202530[2167]LysProGlyLysValProGinLeuLeulieAspAlaAlaSerThrLeu[2168]354045[2169]GinSerGlyValProSerArgPheSerGlySerGlySerGlyThrAsp[2170]505560[2171]PheThrLeuThrlieSerSerLeuGinProGluAspValAlaThrTyr[2172]65707580[2173]TyrCysGinLysTyrAsnSerAlaProPheThrPheGlyProGlyThr[2174]859095[2175]LysValAsplieLysArgThrValAlaAla[2176]100105[2177]SequenceID151[2178]tctccagccaccctgtctgtgtcgccaggggaaagagccaccctctcctgcagggccagt60[2179]cagagtattagcagcaacttagcctggtaccagcagagacctggccaggctcccaggctc120[2180]ctcatctatgatgcatccaccagggccactggtgtcccagccaggttcagtggcagtggg180[2181]tctgggacagagtacactctcaccatcagcagcctgcagtctgaagattttgcagtttat240[2182]tactgtcagcagtataagaactggcctccgtactcttttggccaggggaccaagctggac300[2183]ataaaacgaactgtggctgcacc323[2184]SequenceID152[2185]SerProAlaThrLeuSerValSerProGlyGluArgAlaThrLeuSer[2186]151015[2187]CysArgAlaSerGinSerlieSerSerAsnLeuAlaTrpTyrGinGin[2188]202530[2189]ArgProGlyGinAlaProArgLeuLeulieTyrAspAlaSerThrArg[2190]354045[2191]AlaThrGlyValProAlaArgPheSerGlySerGlySerGlyThrGlu[2192]505560[2193]TyrThrLeuThrlieSerSerLeuGinSerGluAspPheAlaValTyr[2194]65707580[2195]TyrCysGinGinTyrLysAsnTrpProProTyrSerPheGlyGinGly[2196]859095[2197ThrLysLeuAsplieLysArgThrValAlaAla[2198100105[2199SequenceID153[2200tctccagccaccctgtctgtgtctccaggggaaagagccaccctctcctgcagggccagt60[2201cagagtgttagcagcaacttagcctggtaccagcagaaagttggccaggctcccaggctc120[2202ctcatctatggtgcatccagcagggccactggtatcccagccaggttcagtggcactggg180[2203tctgggacagagttcactctcaccatcagcagcctgcagtctgaagattttgcagtttat240[2204tactgtcagcagtataatgactggtacacttttggccaggggaccaagctggagatcaaa300[2205cgaactgtggctgcacc317[2206SequenceID154[2207SerProAlaThrLeuSerValSerProGlyGluArgAlaThrLeuSer[2208151015[2209CysArgAlaSerGinSerValSerSerAsnLeuAlaTrpTyrGinGin[2210202530[2211LysValGlyGinAlaProArgLeuLeulieTyrGlyAlaSerSerArg[2212354045[2213AlaThrGlylieProAlaArgPheSerGlyThrGlySerGlyThrGlu[2214505560[2215PheThrLeuThrlieSerSerLeuGinSerGluAspPheAlaValTyr[221665707580[2217TyrCysGinGinTyrAsnAspTrpTyrThrPheGlyGinGlyThrLys[2218859095[2219LeuGlulieLysArgThrValAlaAla[2220100105[2221SequenceID155[2222tctccaggcaccctgtctgtgtctccagggggaagagccaccctctcctgcagggccagt60[2223cagagtgttggcagcaacttagtctggtatcaacataaacctggccaggctcccagactc120[2224ctcatctatggtgcatccaccagggccactggtatcccagccaggtttagtggcagtggg180[2225tctgggacagagttcactctcaccatcagcggcctgcagtctgaagattttgcaatttat240[2226tactgtcagcagtataataattggcctcgcgggacgttcggccaagggaccaaggtggaa300[2227gtcaaacgaactgtggctgcacc323[2228SequenceID156[2229SerProGlyThrLeuSerValSerProGlyGlyArgAlaThrLeuSer[2230151015[2231CysArgAlaSerGinSerValGlySerAsnLeuValTrpTyrGinHis[2232202530[2233LysProGlyGinAlaProArgLeuLeulieTyrGlyAlaSerThrArg[2234354045[2235AlaThrGlylieProAlaArgPheSerGlySerGlySerGlyThrGlu[2236505560[2237PheThrLeuThrlieSerGlyLeuGinSerGluAspPheAlalieTyr[223865707580[2239TyrCysGinGinTyrAsnAsnTrpProArgGlyThrPheGlyGinGly[2240859095[2241ThrLysValGluValLysArgThrValAlaAla[2242100105[2243SequenceID157[2244tctccaggcaccctgtctglgtctccaggggagagagccaccctctcctgcagggccagt60[2245cagaatattgacagcttcttagcctggtaccagcagaaacctggccaggctcccaggctc120[2246ctcatttatggtgcgtccaccagggccactggtatcccagccaggttcagtggcagtggg180[2247tctgggacagaattcactctcaccattagcagcctgcagtctgaagactttgcagtttat240[2248tactgtcaacagtatgataactggcctccggccacttttggccaggggaccaagctggag300[2249atgaaacgaactgtggctgcacc323[2250SequenceID158[2251SerProGlyThrLeuSerValSerProGlyGluArgAlaThrLeuSer[2252151015[2253CysArgAlaSerGinAsnlieAspSerPheLeuAlaTrpTyrGinGin[2254202530[2255LysProGlyGinAlaProArgLeuLeulieTyrGlyAlaSerThrArg[2256354045[2257AlaThrGlylieProAlaArgPheSerGlySerGlySerGlyThrGlu[2258505560[2259PheThrLeuThrlieSerSerLeuGinSerGluAspPheAlaValTyr[226065707580[2261TyrCysGinGinTyrAspAsnTrpProProAlaThrPheGlyGinGly[2262859095[2263ThrLysLeuGluMetLysArgThrValAlaAla[2264100105[2265SequenceID159[2266tctccagccaccctgtctglgtctccaggggacagagtcaccctctcctgcagggccagt60[2267cacagtgttagtagcaacttagcctggtaccagcagaaacctggccaggctcccaggctc120[2268ctcgtctatgatgcatccaccagggccactgatgtcccagccaggttcagtggcagtggg180[2269tctgggacagaattcactctcaccatcagcagcctgcagtctgaagattttgcagtttat240[2270tactgtcagcagtataataactggcctctgtggacgctcggccaagggaccaaggtggaa300[2271atcaaacgaactgtggctgcacc323[2272SequenceID160[2273SerProAlaThrLeuSerValSerProGlyAspArgValThrLeuSer[227415101585[2275CysArgAlaSerHisSerValSerSerAsnLeuAlaTrpTyrGinGin[2276202530[2277LysProGlyGinAlaProArgLeuLeuValTyrAspAlaSerThrArg[2278354045[2279AlaThrAspValProAlaArgPheSerGlySerGlySerGlyThrGlu[2280505560[2281PheThrLeuThrlieSerSerLeuGinSerGluAspPheAlaValTyr[228265707580[2283TyrCysGinGinTyrAsnAsnTrpProLeuTrpThrLeuGlyGinGly[2284859095[2285ThrLysValGlulieLysArgThrValAlaAla[2286100105[2287SequenceID161[2288tctccaggcaccctgtctttgtctccaggggaaagagccaccctctcctgcagggccagt60[2289cagactgttttcagccgctacttagcctggtaccagcagaaacctgggcggtctcccagg120[2290ctcctcatctatgttgcatccagcagggccactggcatcccagacaggttcagtggcagt180[2291gggtctgggacagacttcactctcaccatcagcagactggagcctgaagattttgcagtg240[2292tattactgtcagcaatatggtagctcaccgtacacttttggccaggggaccaaggtggag300[2293atcaaacgaactgtggctgcacc323[2294SequenceID162[2295SerProGlyThrLeuSerLeuSerProGlyGluArgAlaThrLeuSer[2296151015[2297CysArgAlaSerGinThrValPheSerArgTyrLeuAlaTrpTyrGin[2298202530[2299GinLysProGlyArgSerProArgLeuLeulieTyrValAlaSerSer[2300354045[2301ArgAlaThrGlylieProAspArgPheSerGlySerGlySerGlyThr[2302505560[2303AspPheThrLeuThrlieSerArgLeuGluProGluAspPheAlaVal[230465707580[2305TyrTyrCysGinGinTyrGlySerSerProTyrThrPheGlyGinGly[2306859095[2307ThrLysValGlulieLysArgThrValAlaAla[2308100105[2309SequenceID163[2310tctccaggcaccctgtccttgtctccaggggaaagagccaccctctcctgcagggccagt60[2311cagagtgttagtagtaggtacttagcctggtaccagcagaaacctggccaggctcccagg120[2312ctcctcatctatggtgcatccagcagggccactggcatcccagacaggttcagtggcagt180[2313gggtctgggacagacttcactctcaccatcaacagactggagcctgaagattttgcagtg24086[2314]tattactgtcagcagtatggtacctcaccg[2315]atcaaacgaactgtggctgcacc[2316]SequenceID164[2317]SerProGlyThrLeuSerLeuSer[2318]15[2319]CysArgAlaSerGinSerValSer[2320]20[2321]GinLysProGlyGinAlaProArg[2322]3540[2323]ArgAlaThrGlylieProAspArg[2324]5055[2325]AspPheThrLeuThrlieAsnArg[2326]6570[2327]TyrTyrCysGinGinTyrGlyThr[2328]85[2329]ThrLysLeuGlulieLysArgThr[2330]100[2331]SequenceID165[2332]tctccaggcaccctgtctttgtctccaggg[2333]gagagcataagcagcagctacttagcctgg[2334]ctcctcatctatggtgcatccaacagggcc[2335]gggtctgcgacagacttcactctcaccatc[2336]tattactgtcagcgttatgatacctcactc[2337]gaaatcaaacgaactgtggctgcacc[2338]SequenceID166[2339]SerProGlyThrLeuSerLeuSer[2340]15[2341]CysArgAlaSerGluSerlieSer[2342]20[2343]GinLysProGlyGinAlaProArg[2344]3540[2345]ArgAlaSerGlylieProAspArg[2346]5055[2347]AspPheThrLeuThrlieSerArg[2348]6570[2349]TyrTyrCysGinArgTyrAspThr[2350]85[2351]GlyThrLysValGlulieLysArg[2352]100tacacttttggccaggggaccaagctggag300323ProGlyGluArgAlaThrLeuSer1015SerArgTyrLeuAlaTrpTyrGin2530LeuLeulieTyrGlyAlaSerSer45PheSerGlySerGlySerGlyThr60LeuGluProGluAspPheAlaVal7580SerProTyrThrPheGlyGinGly9095ValAlaAla105gaaagagccaccctctcctgcagggccagt60taccagcagaaacctggccaggctcccagg120tctggcatcccagacaggttcattggcagt180agcagactggagcctgaagattttgcagtg240cggaggacgttcggccaagggaccaaggtg300326ProGlyGluArgAlaThrLeuSer1015SerSerTyrLeuAlaTrpTyrGin2530LeuLeulieTyrGlyAlaSerAsn45PhelieGlySerGlySerAlaThr60LeuGluProGluAspPheAlaVal7580SerLeuArgArgThrPheGlyGin9095ThrValAlaAla10587[2353SequenceID167[2354tctccaggcagcctgtctttgtctccaggggagagagccaccctctcttgcagggccagt60[2355cagagtgtgaggagcaactacgtagcctggtaccagaaggaacctggccgggctccccga120[2356ctcctcatctatggtgcatccaccagggccagtggcatcccagacaggttcagtggcagt180[2357gggtctggggcagacttcactctcaccatcagtggactggagcctgaagattttgcagtg240[2358tattactgtcagcagtatggtagctcaccggggacttttggccaggggacgaggctggag300[2359atcaaacgaactgtggctgcacc323[2360SequenceID168[2361SerProGlySerLeuSerLeuSerProGlyGluArgAlaThrLeuSer[2362151015[2363CysArgAlaSerGinSerValArgSerAsnTyrValAlaTrpTyrGin[2364202530[2365LysGluProGlyArgAlaProArgLeuLeulieTyrGlyAlaSerThr[2366354045[2367ArgAlaSerGlylieProAspArgPheSerGlySerGlySerGlyAla[2368505560[2369AspPheThrLeuThrlieSerGlyLeuGluProGluAspPheAlaVal[237065707580[2371TyrTyrCysGinGinTyrGlySerSerProGlyThrPheGlyGinGly[2372859095[2373ThrArgLeuGlulieLysArgThrValAlaAla[2374100105[2375SequenceID169[2376tctccagactccctgcctgtgtctctgggcgagagggccaccatcaactgcaagtccagc60[2377cagactattttatatggctccagtaataagaattccttggcttggtaccagcagaaacca120[2378ggacagcctcctaggctgctcatttcctgggcatctacccgggaatccggggtccctgac180[2379cgattcagtggcagcgggtctgggacagatttcactctcaccatcagtggcctgcaggct240[2380gaggatgtggcagtttattactgtcaacaatatcattctgttccgtggacgttcggccag300[2381gggaccaaggtggaattcaaacgaactgtggctgcacc338[2382SequenceID170[2383SerProAspSerLeuProValSerLeuGlyGluArgAlaThrlieAsn[2384151015[2385CysLysSerSerGinThrlieLeuTyrGlySerSerAsnLysAsnSer[2386202530[2387LeuAlaTrpTyrGinGinLysProGlyGinProProArgLeuLeulie[2388354045[2389SerTrpAlaSerThrArgGluSerGlyValProAspArgPheSerGly[2390505560[2391SerGlySerGlyThrAspPheThrLeuThrlieSerGlyLeuGinAla6570GluAspValAlaValTyrTyrCys85ThrPheGlyGinGlyThrLysVal100SequenceID171tctccagactccctgcctgtgtctctgggccagactattttatacggctccagtaataagggacagcctcctaggctgctcatttcctggcgattcagtggcagcgggtctgggacagatgaggatgtggcagtttattactgtcaacaagggaccaaggtggaattcaaacgaactgtgSequenceID1727580GinGinTyrHisSerValProTrp9095GluPheLysArgThrValAlaAla105110gagagggccaccatcaactgcaagtccagcaattccttggcttggtaccagcagaaaccagcatctacccgggaatccggggtccctgacttcactctcaccatcagtggcctgcaggcttatcattctgttccgtggacgttcggccaggctgcaccSerProAspSerLeu15CysLysSerSerGinProValSerLeuThrlieLeuLeuAlaTrp35AlaSer20TyrGinGinLysSerTrp50GlySerThrArgSer65GluAspValAlaGlu55PhePro40SerTyr25GlyGly10GlyGluArgAlaThrSerSerAsnSerGlyThrAsp70TyrTyrCysGinGinProProGlyValProThrLeuThrAsp60SerArg45ArgLys30LeulieAsn15AsnSerLeuliePheSerGlyVal85GlyThrLysValThrPheGlyGin100SequenceID173tctccagactccctgcctgtgtctctgggccagactattttatacggctccagtaataagggacagcctcctaggttgctcatttcctggcgattcagtggcagcgggtctgggacagatgaagatgtggcagtttattactgtcaacaagggaccaaggtggaattcaaacgaactgtgSequenceID174SerProAspSerLeuProValSer15CysLysSerSerGinThrlieLeu20Glu105Gin90Phelie75TyrHisSerValGlyLeuGinAla80TrpLysArgThrVal110Pro95AlaAlagagagggccaccatcaactgcaagtccagcaattcctkggcttggtaccagcagaaaccagcctctacccgggaatccggggtccctgacttcactctcaccatcagtggcctgcaggcttatcattctgttccgtggacgttcggccaggctgcaccLeuGlyGluArgAlaThrlieAsn1015TyrGlySerSerAsnLysAsnSer25306012018024030033860120180240300338[2431]LeuAlaTrpTyrGinGinLysProGlyGinProProArgLeuLeulie[2432]354045[2433]SerTrpAlaSerThrArgGluSerGlyValProAspArgPheSerGly[2434]505560[2435]SerGlySerGlyThrAspPheThrLeuThrlieSerGlyLeuGinAla[2436]65707580[2437]GluAspValAlaValTyrTyrCysGinGinTyrHisSerValProTrp[2438]859095[2439]ThrPheGlyGinGlyThrLysValGluPheLysArgThrValAlaAla[2440]100105110[2441]SequenceID175[2442]tctccagactccctgcctgt:gtctctgggcgagagggccaccatcaactgcaagtccagc60[2443]cagactattttatacggctccagtaataagaattccttggcttggtaccagcagaaacca120[2444]ggacagcctcctaggctgct,catttcctgggcatctacccgggaatccggggtccctgac180[2445]cgattcagtggcagcgggtc:tgggacagatttcactctcaccatcagtggcctgcaggct240[2446]gaagatgtggcagtttatta,ctgtcaacaatatcattccattccgtggacgttcggccag300[2447]gggaccaaggtggacttcaaacgaactgtggctgcacc338[2448]SequenceID176[2449]SerProAspSerLeuProValSerLeuGlyGluArgAlaThrlieAsn[2450]151015[2451]CysLysSerSerGinThrlieLeuTyrGlySerSerAsnLysAsnSer[2452]202530[2453]LeuAlaTrpTyrGinGinLysProGlyGinProProArgLeuLeulie[2454]354045[2455]SerTrpAlaSerThrArgGluSerGlyValProAspArgPheSerGly[2456]505560[2457]SerGlySerGlyThrAspPheThrLeuThrlieSerGlyLeuGinAla[2458]65707580[2459]GluAspValAlaValTyrTyrCysGinGinTyrHisSerlieProTrp[2460]859095[2461]ThrPheGlyGinGlyThrLysValAspPheLysArgThrValAlaAla[2462]100105110[2463]SequenceID177[2464]tctccagactccctggctgt:gtctctgggcgagagggccaccatcaactgcaagtccagc60[2465]cagagtgttttatacagctccaacaataagaacttcttagcttggtaccagcagaaacca120[2466]ggacagcctcctaaactgct,catttactgggcatctacccgggaatccggggtccctgac180[2467]cgattcagtggcagcgggtc:tgggacagagttcactctcaccatcagcaacctgcaggct240[2468]gaagatgtggcagattatta,ctgtcagcaatattatggtagtcctccgtggacgttcggc300[2469]caagggaccagggtggaaat丨caaacgaactgtggctgcacc34190SequenceIDSerProAsp1CysLeuTyrSer65GluTrpLysAlaTrp50GlyAspThrSerTrp35AlaSerValPhe178SerSer20TyrSerGlyAlaLeu5GinGinThrThrAsp85GinAlaSerGinArgGlu70TyrGlyValValLysGlu55PheTyrThrSerLeuLeuTyr25ProGly40SerGlyThrLeuCysGinGly10SerGinValThrGin90GluGluSerArgAsnProProProlie75TyrlieAsp60SerTyrLysAlaAsnLys45ArgAsnGlyArgThrLys30Leulie15AsnLeuPheSerLeuGinSerPro95ValAsnPhelieGlyAla80ProAlaGlyGinGlyThrArgValGlulieLysArgThr100105110AlaSequenceID179tctccagactccctggctgtgtctctgggcgagagggccaccatcaactgcaagtccagtcagagtgttttatacatctccaacaataagaactgcttagcttggtaccagcagaaaccaggacagcctcctaagctgctcatttactgggcatctacccgggaatccggggtccctgaccgattcagtggcagcgggtctgggacagatttcactctcaccatcagcagcctgcaggctgaagatgtggcagtttattactgtcagcagtattatagtactccttggacgttcggccaagggaccaaggtggaaatcaaacgaactgtggctgcaccSequenceID180SerProAspSer1CysLeuTyrSer65GluThrLysAlaTrp50GlyAspPheSerTrp35AlaSerValGlySequenceIDSer20TyrSerGlyAlaGin100181Leu5GinGinThrThrVal85GlyAlaSerGinArgAsp70TyrThrValValLysGlu55PheTyrLysSerLeuLeuTyr25ProGly40SerGlyThrLeuCysGinValGlu105Gly10lieGinValThrGin90lieGluSerProProlie75TyrLysArgAsnProAsp60SerTyrArgAlaAsnLys45ArgSerSerThrThrLys30LeuPheLeuThrVal110lie15AsnLeuSerGinPro95AlaAsnCyslieGlyAla80TrpAla6012018024030033891[2509tctccagactccctggctglgtctctgggcgagagggccaccatcaactgcaagtccagc60[2510cagcgtgttttccacaactcCclclCclcltclclclaactggttggcttggtaccagcagaaaccg120[2511ggacaacctcctaagctgctcatttactgggcatctacacgggaatccggggtccctgac180[2512cgattcagtggcagcgggtctgggacagatttcactctcaccatcagcagcctgcaggct240[2513gaagatgtggcagtttattactgtcagcagtattatagtgctccccggacgttcggccaa300[2514gggaccaaggtggaaatcaaacgaactgtggctgcacc338[2515SequenceID182[2516SerProAspSerLeuAlaValSerLeuGlyGluArgAlaThrlieAsn[2517151015[2518CysLysSerSerGinArgValPheHisAsnSerAsnAsnLysAsnTrp[2519202530[2520LeuAlaTrpTyrGinGinLysProGlyGinProProLysLeuLeulie[2521354045[2522TyrTrpAlaSerThrArgGluSerGlyValProAspArgPheSerGly[2523505560[2524SerGlySerGlyThrAspPheThrLeuThrlieSerSerLeuGinAla[252565707580[2526GluAspValAlaValTyrTyrCysGinGinTyrTyrSerAlaProArg[2527859095[2528ThrPheGlyGinGlyThrLysValGlulieLysArgThrValAlaAla[2529100105110[2530SequenceID183[2531tctccagactccctggctglgtctctgggcgagagggccaccatcaactgcaagtccagc60[2532cagagtgttttatacagctccagcaatgagaactacttagctkggtaccaacagaagcca120[2533gggcagcctcctaaactgctcatttactgggcatctacccgggaatccggggtccctgac180[2534cgattcaatgtcagcaggtctgggacagatttcactctcaccatcagcagcctgcaggct240[2535gcagatgtggcagtttattactgtcaccaatattacagtactccgtacacttttggccag300[2536gggaccaggctggagatcaagcgaactgtggctgcacc338[2537SequenceID184[2538SerProAspSerLeuAlaValSerLeuGlyGluArgAlaThrlieAsn[2539151015[2540CysLysSerSerGinSerValLeuTyrSerSerSerAsnGluAsnTyr[2541202530[2542LeuAlaTrpTyrGinGinLysProGlyGinProProLysLeuLeulie[2543354045[2544TyrTrpAlaSerThrArgGluSerGlyValProAspArgPheAsnVal[2545505560[2546SerArgSerGlyThrAspPheThrLeuThrlieSerSerLeuGinAla[254765707580[2548AlaAspValAlaValTyrTyrCysHisGinTyrTyrSerThrProTyr[2549859095[2550ThrPheGlyGinGlyThrArgLeuGlulieLysArgThrValAlaAla[2551100105110[2552SequenceID185[2553tctccagactccctggctgtgtctctgggcgagagggccaccatcaactgcaagtccagc60[2554cagagtgttttatacagctccagcaatgagaactacttagcttggtaccaacagaagcca120[2555gggcagcctcctaaactgctcatttactgggcatctacccgggaatccggggtccctgac180[2556cgattcagtggcagcgggtctgggacagatttcactctcaccatcagcagcctgcaggct240[2557gcagatgtggcagtttattactgtcaccaatattacagtactccgtacacttttggccag300[2558gggaccaggctggagatcaagsgaactgtggctgcacc338[2559SequenceID186[2560SerProAspSerLeuAlaValSerLeuGlyGluArgAlaThrlieAsn[2561151015[2562CysLysSerSerGinSerValLeuTyrSerSerSerAsnGluAsnTyr[2563202530[2564LeuAlaTrpTyrGinGinLysProGlyGinProProLysLeuLeulie[2565354045[2566TyrTrpAlaSerThrArgGluSerGlyValProAspArgPheSerGly[2567505560[2568SerGlySerGlyThrAspPheThrLeuThrlieSerSerLeuGinAla[256965707580[2570AlaAspValAlaValTyrTyrCysHisGinTyrTyrSerThrProTyr[2571859095[2572ThrPheGlyGinGlyThrArgLeuGlulieLysArgThrValAlaAla[2573100105110[2574SequenceID187[2575tctccagactccctggctgtgtctctgggcgagagggccaccatcaactgcaagtccagc60[2576cagagtgttttatacaactccaacaataagaactacttagcttggtaccagcagagacca120[2577ggacagcctcctaagctgctcattcgctgggcatctacccgggactccggggtccctgac180[2578cgattcagtggcagcgggtctgggacagatttcactctcaccatcagcagcctgcaggct240[2579gaggatgtggcagtttattactgtcagcaatattatagtagtcctcccactttcggccct300[2580gggaccaaagtggatatcaaacgaacggtggctgcacc338[2581SequenceID188[2582SerProAspSerLeuAlaValSerLeuGlyGluArgAlaThrlieAsn[2583151015[2584CysLysSerSerGinSerValLeuTyrAsnSerAsnAsnLysAsnTyr[2585202530[2586LeuAlaTrpTyrGinGinArgProGlyGinProProLysLeuLeulie9335ArgTrpAla50SerGlySer65GluAspValThrPheGlySequenceIDSerThrArgThrGlyAlaPro100189Asp70ValTyr85GlyThrAsp55PheTyrLys40SerThrCysGinValAsp105GlyValProLeuThrGin90lielie75TyrAsp60Ser45ArgPheSerGlySerLeuGinAla80ProTyrSerSerLysArgThrVal110Pro95AlaAlatctccagactccctggctgtgtctctgggcgagagggccaccatcaactgcaggtccagccagagtctttcatccacctccgacaataacaaccacttaagttggtaccaggtgaaaccaggacagtctcctagactgctcatttactgggcatctaaccgggaatcaggggtccctgaccgattcagcggcagcgggtctgggacagatttcactctcaccatcagcagcctgcaggctgaagatgtggcactctattactgtctacactattctaatactttttggacattcggccaagggaccagggtggaaatcaaacgaactgtggctgcaccSequenceID190AlaValSerLeuGlyGluSerProAspSerLeu15CysArgSerSerGinLeuSerTrp35AlaSer20TyrTyrSer65GluTrp50GlySerGlyAspValAlaGinSerAsnThrSerLeuSerSer25Gly10ThrArgSerAspAlaThrAsnValLysArgGlu55PheLeu85Asp70TyrTyrCysLeuGinSerProGlyValProThrLeuThrPro40SerHis90lie75TyrAsp60SerArg45ArgAsn30LeulieAsn15AsnHisLeuliePheSerGlySerLeuGinAla80PheTrp95SerAsnThr60120180240300338ThrPheGlyGinGlyThrArgValGlulieLysArgThrValAlaAla[2617]100105110[2618]SequenceID191[2619]caggtgaaactgctcgagtctgggggaggtgtggtacagccgggggggtccctgagactc60[2620]tcctgtgcagcctctggattcagctttagcagctataccatgtcctgggtccgccaggct120[2621]ccagggaaggggctggagtgggtctcaggtattagtggtagtgggagcgcatactacgga180[2622]gactccgtgaagggccggtttaccatctccagagacaattccaagaacacgctgtatctg240[2623]caaatgaacagcctgagagccgaggacacggccgtatattactgtgcgaaagcctccgcc300[2624]cagggggtagtggttctctccgcgggatttcgatactactttaactactggggccaggga360[2625]accctggtcaccgtctcctcagcttccaccaagggcccatcggtcttccccctggcgccc42094[2626][2661][2662]tgctccaggagcacctctgggggcacagcggcccSequenceID192LysLeuLeu5ArgLeuSer454Gin1SerThrSerGly65GinLysTyrSerValLeuMetGly50ArgMetAlaPheSer35liePheAsnSerAsn115ThrLys130SerGlyLeu20TrpSerThrSerAla100TyrGlyGlyValGlylieLeu85GinTrpProThrGluCysArgSerSer70ArgGlyGlySerSerAlaGinGly55ArgAlaValGinVal135AlaGlyGlyGly10GlyAlaSer25AlaPro40SerAlaAspAsnGluAspValVal105GlyThr120PheProGlyTyrSerThr90LeuLeuLeuValPheLysTyrLys75AlaSerValAlaValSerGlyGly60AsnValAlaThrPro140GinProPheLeu45AspThrTyrGlyVal125CysSer30GluSerLeuTyrPhe110SerGly15SerTrpValTyrCys95ArgSerSerArgGlyTyrValLysLeu80AlaTyrAlaSerThrSerGlyGlyThrAla145150SequenceID193caggtgaaactgctcgagtctgggggaggcttggtacagctcctgtgcagcctctggattcacctttagcagctatgccaccagggaaggggctggagtgggtctcagcttttagtggtagcagactccgtgaagggccggttcaccatctccagagacactgcaaatgaacagcctgagagccgaggacacggccgtatgcccagggggtagtggttctctccgcgggatttcgatactggaaccctggtcaccgtctcctcagcttccaccaagggccccctgctccaggagcacctctgggggcacagcggcccSequenceID194LeuLeuGluSerGlyGlyGlyLeu510LeuSerCysAlaAlaSerGlyPhe2025TrpValArgGinAlaProGlyLys40SerGlySerGlyGlyGlyThrTyrctggggggtccctgagactctgagctgggtccgccaggctgtggaggtggcacatactacattccaagaacacgctgtatattactgtgcgaaagcctccactttaactactggggccagcatcggtcttccccctggcgGinValLys1SerLeuArgAlaMetSer35SerAlaPheValThrGlyTyrGinProPheSer30LeuGlu45AlaAspGly15SerTrpSerGlyTyrValVal60120180240300360420457Lys65LeuAlaTyrAla50GlyArgPheThrGinMetAsnSer85Alalie70Leu55SerLysAlaTyrSer130ThrPhe115ThrSer100AsnLysSerGlyTyrGlyProGlyArgGinGlyTrpGlyArgAspAsnAlaGluSer135AlaAlaValVal105GinGly120ValPheAsp90Val60LysAsnThrLeuAlaValTyrLeuSerAlaSer75ThrTyr80CysThrLeuValProLeuAla140Thr125ProGly110ValTyr95PheArgSerSerCysSerArgSerThrSerGlyGlyThr145150SequenceID195caggtgaaactgctcgagtctgggggaggcttggtacagctcctgtgcagcctctggattcacctttagcagctataccaccagggaaggggctggagtgggtctcagcttttagtggtagcagactccgtgaagggccggttcaccatctccagagacactgcaaatgaacagcctgagagccgaggacacggccgtattccgcccagggggttctcgttctctccgcgggatttcgatcagggaaccctggtcaccgtctcctcagcttccaccaagggcgccctgctccaggagcacctctgggggcacagcggcccSequenceID196GluSerGlyGlyGlyLeuctggggggtccctgagactc60tgtcctgggtccgccaggct120gtggaggtggcacatactac180attccaagaacacgctgtat240attactgtgcgaaagccgcc300actactttaactactggggc360gcccatcggtcttccccctg420460Gin1SerValLysLeuLeuArgThrMetSer35PheLeu20TrpLeu5SerCysArgSerAla50GlyArgLys65LeuAlaArgPheGinMetAsnValSerGlySerThrLysTyrAlaAla100TyrPhe115Ser85Serlie70LeuAlaGinGly55SerArgAlaGinAsnTyrTrpAlaSer25AlaPro40GlyGlyArgAspAlaGlu10GlyGlyThrAsnAsp90LeuValPheThrGlyGinProPheLysTyrSer75ThrTyr60LysLeu45AlaSer30GluAsnAlaValAspThrLeuTyrGlyGly15SerTyrTrpValSerValGlyVal105GlyGinGly120ValLeuSerThrLeuVal125Ala110ThrTyr95GlyTyr80CysPheValSer962704]SerAlaSerThrLysGlyProSer2705]1301352706]ArgSerThrSerGlyGlyThrAla2707]1451502708]SequenceID1972709]caggtgaaactgctcgagtctgggggaggc2710]tcctgtgcagcctctggattcacctttagc2711]ccagggaaggggctggagtgggtctcagct2712]gcagactccgtgaagggccggttcaccatc2713]ctgcaaatgaacagcctgagagccgaggac2714]gcggtagtggttctctccgcgggatttcga2715]ctggtcaccgtctcctcagcttccaccaag2716]tccaggagcacctctgggggcacagcggcc2717]SequenceID1982718]GinValLysLeuLeuGluSerGly2719]152720]SerLeuArgLeuSerCysAlaAla2721]202722]AlaMetSerTrpValArgGinAla2723]35402724]SerAlaPheSerGlySerGlyGly2725]50552726]LysGlyArgPheThrlieSerArg2727]65702728]LeuGinMetAsnSerLeuArgAla2729]852730]AlaLysAlaSerAlaValValVal2731]1002732]PheAsnTyrTrpGlyGinGlyThr2733]1151202734]ThrLysGlyProSerValPhePro2735]1301352736]SerGlyGlyThrAlaAla2737]1451502738]SequenceID1992739]caggtgaaactgctcgagtctgggggaggc2740]tcctgtgcagcctctggattcacctttagc2741]ccagggaaggggctggagtgggtctcagct2742]gcagactccgtgaagggccggttcaccatcValPheProLeuAlaProCysSer140Alattggtacagcctggggggtccctgagactc60agctatgccatgagctgggtccgccaggct120tttagtggtagtggaggtggcacatactac180tccagagacaattccaagaacacgctgtat240acggccgtatattactgtgcgaaagcctcc300tactactttaactactggggccagggaacc360ggcccatcggtcttccccctggcgccctgc420c451GlyGlyLeuValGinProGlyGly1015SerGlyPheThrPheSerSerTyr2530ProGlyLysGlyLeuGluTrpVal45GlyThrTyrTyrAlaAspSerVal60AspAsnSerLysAsnThrLeuTyr7580GluAspThrAlaValTyrTyrCys9095LeuSerAlaGlyPheArgTyrTyr105110LeuValThrValSerSerAlaSer125LeuAlaProCysSerArgSerThr140ttggtacagcctggggggtccctgagactc60agctatgccatgagctgggtccgccaggct120tttagtggtagtggaggtggcacatactac180tccagagacaattccaagaacacggtgtat240[2743]ctgcaaatgaacagcctgagacctgaggacacggctatgtattactgtgtgaaagatcac300[2744]gtagcagtgcctggttttctctcttactttgaccactggggccagggaaccctggtcacc360[2745]gtctcctcagcttccaccaagggcccatcggtcttccccctggcgccctgctccaggagc420[2746]acctctgggggcacagcggcCC442[2747]Sequence工D200[2748]GlnValLysLeuLeuGluSetGlyGlyGlyLeuValGlnProGlyGly[2749]l5lo15[2750]SetLeuArgLeuSetCysAlaAlaSetGlyPhe／hrPheSetSet／yr[2751]202530[2752]AlaMetSet／rpValArgGlnAlaProGlyLysGlyLeuGlu／rpVal[2753]354045[2754]SetAlaPheSetglySetglyglygly／hr／yr／yrAlaAspSetVal[2755]505560[2756]LysGlyArgPhe／hrIleSetArgAspAsnSetLysAsn／hrVal／yr[2757]65707580[2758]LeuGlnMetAsnSetLeuArgProGluAsp／hrAlaMet／yr／yrCys[2759]859095[2760]ValLysAspHiSValAlaValProGlyPheLeuSet／yrPheAspHiS[2761]100105110[2762]／rpGlyGlnGly／hrLeuVal／hrValSetSetAlaSet／hrLysGly[2763]115120125[2764]ProSetValPheProLeuAlaProCysSetArgSet／hrSetGlyGly[2765]130135140[2766]／hrAlaAla[2767]145[2768]Sequence工D20l[2769]caggtgaaactgctcgagtctgggggaggcttggtacagcctggggggtccctgagactc60[2770]tcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggct120[2771]ccagggaaggggctggagtgggtctcagcttttagtggtagtggaggtggcacatactac180[2772]gcagactccgtgaagggccgattcaccatttccagagacaattccaagaacacggtgtat240[2773]ctgcaaatgaacagcctgagacctgaggacacggctatgtattactgtgtgaaagatcac300[2774]gtagcagtgcctggttttctctcttactttgaccactggggccagggaaccctggtcacc360[2775]gtctcctcagcctccaccaagggcccatcggtcttccccctggcgccctgctccaggagc420[2776]acctctgggggcacagcggcCC442[2777]Sequence工D202[2778]GlnValLysLeuLeu61uSetGlyGlyGlyLeuValGlnProGlyGly[2779]l5lo15[2780]SetLeuArgLeuSetCysAlaAlaSetGlyPhe／hrPheSetSet／yr[2781]202530AlaMetSerLys65LeuValTrpProAla50GlyGinLysGlySer35PheArgMetAspTrpSerPheAsnHis100GlyGin115ValPheValGlyThrSer85ValThrProSer130ThrAlaAla145SequenceID203caggtgaaactgctcgagtctcctgtgcagcgtctggattccaggcaaggggctggagtgggagactctgtgaagggccgctgcagatgaacagcctgagattgagagattaatgtctggtcagcctccaccaagggcccgggggcacagcggcccSequenceID204GinValLysLeuArgSerlie70LeuAlaLeuLeuGinAlaPro40GlyGlyGly55SerArgValValAla135ArgAspProGluProGly105ThrVal120ProCysGlyThrAsnAsp90PheSerSerLysGlyTyrSer75ThrLeuSerArgTyr60LysAlaSerAlaSer140Leu45AlaAsnMetTyrSer125ThrGluAspThrTyrPhe110ThrTrpSerValTyr95AspLysSerGlyValValTyr80CysHisGlyGlytgggggaggcgtggtccagcctgggaggtcccttagactc60catcttcagtagttatggcatgcattgggtccgccaggct120ggtggcgtttataccatttgatggaaagaacaaatactat180attcaccatctccagagacaattccgagaacacgctgtat240aactgatgacacggctgtgtattactgtgcgaaagaccgc300tcttgactactggggccagggatccctggtcaccgtctcc360atcggtcttccccctggcaccctcctccaagagcacctct4204361SerGlyAlaLys65LeuLeuArgMetPhe50GlyGinAlaLysHis35lieArgMetAspLeu20TrpProPheAsnArgLeu5SerValPheThrSer85lieGluCysArgAsplie70LeuSerAlaGinGly55SerGlyGlyGly10GlyArgGluArgAlaSer25AlaPro40LysAsnArgAspThrAspLeuMetGlyLysAsnAsp90SerValPheLysTyrSer75ThrVallieGlyTyr60GluGinProPheAlaGlyLeuLeu45GlyAsnValAspSer30GluAspThrTyrTyrGly15SerTrpSerLeuArgTyrValValTyr80CysTyr95TrpGly[2821]100105110[2822]GinGlySerLeuValThrValSerSerAlaSerThrLysGlyProSer[2823]115120125[2824]ValPheProLeuAlaProSerSerLysSerThrSerGlyGlyThrAla[2825]130135140[2826]Ala[2827]145[2828]Sequence；ID205[2829]caggtgaaactgctcgagtctggcccaggactggtggagccttcacagaccctgaccctc60[2830]acctgctctgtctctggcgg;ctccatcaccagtgatagttactactggggctggatccgc120[2831]cagcacccagggaagggcctggagtggattgggtacatcgttcacagtgggatcgcctac180[2832]tacaacccggccctcaaggg;tcgagctaccatatcactagacacctctaagaaccgggtg240[2833]tccctgaagctgagctctgc:gacggccgcggacacggccgtgtattactgtgcgagagat300[2834]agtagccgtaaggatcgagg;cttcagagcctggttcgacccctggggccagggaaccctg360[2835]gtcaccgtctcctcagcctccaccaagggcccatcggtcttccccctggcgccctgctcc420[2836]aggagcacctctgggggcacagcggccc448[2837]Sequence！ID206[2838]GinValLysLeuLeuGluSerGlyProGlyLeuValGluProSerGin[2839]151015[2840]ThrLeuThrLeuThrCysSerValSerGlyGlySerlieThrSerAsp[2841]202530[2842]SerTyrTyrTrpGlyTrplieArgGinHisProGlyLysGlyLeuGlu[2843]354045[2844]TrplieGlyTyrlieValHisSerGlylieAlaTyrTyrAsnProAla[2845]505560[2846]LeuLysGlyArgAlaThrlieSerLeuAspThrSerLysAsnArgVal[2847]65707580[2848]SerLeuLysLeuSerSerAlaThrAlaAlaAspThrAlaValTyrTyr[2849]859095[2850]CysAlaArgAspSerSerArgLysAspArgGlyPheArgAlaTrpPhe[2851]100105110[2852]AspProTrpGlyGinGlyThrLeuValThrValSerSerAlaSerThr[2853]115120125[2854]LysGlyProSerValPheProLeuAlaProCysSerArgSerThrSer[2855]130135140[2856]GlyGlyThrAlaAla[2857]145[2858]Sequence；ID207[2859]caggtgaaactgctcgagtctggcccaggactggtgaagccttcggagaccctgtccctc60acctgcaccgtctctggtggctccatcaatacttatatctggcactggatccggcagtccccagggaagggactggagtggattggtcacatctattacagtgggagctccttcgccaacccgtccctcaagagtcgcatttccatttcagtggccgcctctaagaaccagttcttcctcgatctgaactctgtgacggccgcggacacggccgtctattactgtgcgagagaacgaattctggctagtggctatgggagggactacaactccgggatggacgtctggggccagggaaccctggtcaccgtctcctcagcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggcccSequenceID208GinValLysLeuLeu15ThrLeuSerLeuThr20TrplieGluSerGlyProlieTrpGlyHis50ArgHis35lieCysThrValArgGinTyrTyrSerSer40SerSer25ProGly10GlylieSerlieSer65AspLeuAsnSerArgGluArglie100TrpSer70ThrGly55ValAlaSerAlaAlaAlaAspLeuGlyGlyLysPheAlaSerVal85LeuAlaSerGlyMetAspVal115GlyProSerValGlyGinGlyThr120ProTyr105LeuThr90GlyLys75AlaArgValThrValSerGlyAsn60AsnValAspValThrLysGlyProSerValPhe130135SerGlyGlyThrAlaAla145150SequenceID209LeuAlaProSer140LysProSerGlu15lieAsnThrTyr30LeuGluTrplie45ProSerLeuLysGinPhePheLeu80TyrTyrCysAla95TyrAsnSerGly110SerSerAlaSer125SerLysSerThrSequenceID210GinValLysLeuLeuGluSerGlyAlaGluValLysLysProGlyGlu120180240300360420451caggtgaaactgctcgagtctggggcagaggtgaaaaagcccggggagtctctgaagatc60[2890]tcctgtaagggttctggatacagctttaccagctactggatcggctgggtgcgccagatg120[2891]cccgggaaaggcctggagtggatggggatcatctatcctggtgactctgataccagatac180[2892]agcccgtccttccaaggccaggtcaccatctcagccgacaagtccatcagcaccgcctac240[2893]ctgcagtggagcagcctgaaggcctcggacaccgccatgtattactgtgcgagacccttg300[2894]gatacacgtggcccacactttgactactggggccagggaaccctggtcaccgtctcctca360[2895]gcttccaccaagggcccatcggtcttccccctggcgccctgctccaggagcacctctggg420[2896]ggcacagcggccc433[2899151015[2900SerLeuLyslieSerCysLysGlySerGlyTyrSerPheThrSerTyr[2901202530[2902TrplieGlyTrpValArgGinMetProGlyLysGlyLeuGluTrpMet[2903354045[2904GlylielieTyrProGlyAspSerAspThrArgTyrSerProSerPhe[2905505560[2906GinGlyGinValThrlieSerAlaAspLysSerlieSerThrAlaTyr[290765707580[2908LeuGinTrpSerSerLeuLysAlaSerAspThrAlaMetTyrTyrCys[2909859095[2910AlaArgProLeuAspThrArgGlyProHisPheAspTyrTrpGlyGin[2911100105110[2912GlyThrLeuValThrValSerSerAlaSerThrLysGlyProSerVal[2913115120125[2914PheProLeuAlaProCysSerArgSerThrSerGlyGlyThrAlaAla[2915130135140[2916SequenceID211[2917tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaagt60[2918cagaacattaggaagtatttaaattggtatcagcacaaaccagggaaagcccctaaactc120[2919ctgatctttcttgcatccaatttgcaaagtggagtcgcatccagattcagtggcagtgga180[2920tctggggctgatttcagtctcaccatcagcagtctgcaacctgaagattttgcaacttac240[2921tactgtcaagcttataacaatatccctactttcggccctgggaccaaagtggatatcaga300[2922cgaactgtggctgcacc317[2923SequenceID212[2924SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr[2925151015[2926CysArgAlaSerGinAsnlieArgLysTyrLeuAsnTrpTyrGinHis[2927202530[2928LysProGlyLysAlaProLysLeuLeuliePheLeuAlaSerAsnLeu[2929354045[2930GinSerGlyValAlaSerArgPheSerGlySerGlySerGlyAlaAsp[2931505560[2932PheSerLeuThrlieSerSerLeuGinProGluAspPheAlaThrTyr[293365707580[2934TyrCysGinAlaTyrAsnAsnlieProThrPheGlyProGlyThrLys[2935859095[2936ValAsplieArgArgThrValAlaAla[2937100105[2938SequenceID213[2939tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaagt60[2940cagaacattaggaagtatttaaattggtatcagcacaaaccagggaaagcccctaaactc120[2941ctgatctttcttgcatccaatttgcaaaatggagtcgcatccagattcagtggcagtgga180[2942tctggggctgatttcagtctcaccatcagcagtctgcaacctgaagattttgcaacttac240[2943tactgtcaagcttataacaatatccctactttcggccctgggaccaaagtggatatcaga300[2944cgaactgtggctgcacc317[2945SequenceID214[2946SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr[2947151015[2948CysArgAlaSerGinAsnlieArgLysTyrLeuAsnTrpTyrGinHis[2949202530[2950LysProGlyLysAlaProLysLeuLeuliePheLeuAlaSerAsnLeu[2951354045[2952GinAsnGlyValAlaSerArgPheSerGlySerGlySerGlyAlaAsp[2953505560[2954PheSerLeuThrlieSerSerLeuGinProGluAspPheAlaThrTyr[295565707580[2956TyrCysGinAlaTyrAsnAsnlieProThrPheGlyProGlyThrLys[2957859095[2958ValAsplieArgArgThrValAlaAla[2959100105[2960SequenceID215[2961tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaagt60[2962cagaacattaggaagtatttaaattggtatcagcacaaaccagggaaagcccctaaactc120[2963ctgatctttcttgcatccaatttgcaaagtggagtcgcatccagattcagtggcagtgga180[2964tctggggctgatttcagtctcaccatcagcagtctgcaacctgaagattttgcaacttac240[2965tactgtcaagcttataacaatatccctactttcggccccgggaccaaagtggatatcaga300[2966cgaactgtggctgcacc317[2967SequenceID216[2968SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr[2969151015[2970CysArgAlaSerGinAsnlieArgLysTyrLeuAsnTrpTyrGinHis[2971202530[2972LysProGlyLysAlaProLysLeuLeuliePheLeuAlaSerAsnLeu[2973354045[2974GinSerGlyValAlaSerArgPheSerGlySerGlySerGlyAlaAsp[2975505560[2976PheSerLeuThrlieSerSerLeuGinProGluAspPheAlaThrTyr[297765707580[2978TyrCysGinAlaTyrAsnAsnlieProThrPheGlyProGlyThrLys[2979859095[2980ValAsplieArgArgThrValAlaAla[2981100105[2982SequenceID217[2983tctccatcctccctatctgcatctgtaggagacagagtcaccatcacctgccgggcaagt60[2984cagaccattggcacctatttaaattggtatcagcacaaaccagggaaagcccctaagctc120[2985ctgatctatgttgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtgga180[2986tctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcagcttac240[2987tactgtcaacagagttacggtacccctccaacttttggccaggggaccaagctggagatc300[2988aaacgaactgtggctgcacc320[2989SequenceID218[2990SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr[2991151015[2992CysArgAlaSerGinThrlieGlyThrTyrLeuAsnTrpTyrGinHis[2993202530[2994LysProGlyLysAlaProLysLeuLeulieTyrValAlaSerSerLeu[2995354045[2996GinSerGlyValProSerArgPheSerGlySerGlySerGlyThrAsp[2997505560[2998PheThrLeuThrlieSerSerLeuGinProGluAspPheAlaAlaTyr[299965707580[3000TyrCysGinGinSerTyrGlyThrProProThrPheGlyGinGlyThr[3001859095[3002LysLeuGlulieLysArgThrValAlaAla[3003100105[3004SequencelD219[3005tctccatcctccctatctgcatctgtaggagacagagtcaccatcacctgccgggcaagt60[3006cagaccattggcacctatttaaactggtatcagcacaaaccagggaaagcccctaagctc120[3007ctgatctatgttgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtgga180[3008tctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcagcttac240[3009tactgtcaacagagttacggtacccctccaacttttggccaggggaccaagctggagatc300[3010aaacgaactgtggctgcacc320[3011SequenceID220[3012SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr[3013151015[3014CysArgAlaSerGinThrlieGlyThrTyrLeuAsnTrpTyrGinHis[3015202530[3016]LysProGlyLysAlaProLysLeuLeulieTyrValAlaSerSerLeu[3017]354045[3018]GinSerGlyValProSerArgPheSerGlySerGlySerGlyThrAsp[3019]505560[3020]PheThrLeuThrlieSerSerLeuGinProGluAspPheAlaAlaTyr[3021]65707580[3022]TyrCysGinGinSerTyrGlyThrProProThrPheGlyGinGlyThr[3023]859095[3024]LysLeuGlulieLysArgThrValAlaAla[3025]100105[3026]Sequence；ID221[3027]tctccatcctccctatctgcatctgtaggagacagagtcaccatcacctgccgggcaagt60[3028]cagaccattggcacctatttaaattggtatcagcacaaaccagggaaagcccctaagctc120[3029]ctgatctatgttgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtgga180[3030]tctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcagcttac240[3031]tactgtcaacagagttacggtacccctccaacttttggccaggggaccaagctggagatc300[3032]aaacgaactgtggctgcacc320[3033]SequenceID222[3034]SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr[3035]151015[3036]CysArgAlaSerGin‘ThrlieGlyThrTyrLeuAsnTrpTyrGinHis[3037]202530[3038]LysProGlyLysAlaProLysLeuLeulieTyrValAlaSerSerLeu[3039]354045[3040]GinSerGlyValProSerArgPheSerGlySerGlySerGlyThrAsp[3041]505560[3042]PheThrLeuThrlieSerSerLeuGinProGluAspPheAlaAlaTyr[3043]65707580[3044]TyrCysGinGinSer‘TyrGlyThrProProThrPheGlyGinGlyThr[3045]859095[3046]LysLeuGlulieLys.ArgThrValAlaAla[3047]100105[3048]SequenceID223[3049]tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaagt60[3050]cagagcattagaaattttctaaattggtatcagcagacaccagggaaagcccctaagctc120[3051]ctgatctatgctgcatccagtctgcaaagtggggtcccatcaaagttcagtggcagtgga180[3052]tctgggacagagttcactctcaccatcagcagtctgcaacctgaagattttgccacttat240[3053]tactgtcaacagagttacagtacccctctgacgttcggccaagggaccaaggtggaaatc300[3054]aaacgaactgtggctgcacc320SequenceIDSerProSer1CysThrGinPhe65TyrLysArgAlaProSer50ThrCysValGly35GlyLeuGinGlu224SerSer20LysValThrGinLeu5GinSerAlaSerValGlyAsp10SerlieArgAlaProLysProSerlieSer85LysSer70TyrLys55SerSerLeu40PheAsn25LeuPhelieGlyLeuGinProArgValThrLeuAsnTrpSerArgThrThrValProAla105Leu90AlaTyrSerGlu75ThrAlaGly60AspPheAla45SerPheGlyTyr30SerGlyAlaGinlie15GinThrGinSerLeuThrThrGly95GluTyr80Thrlie100SequenceID225tctccatcctccctgtctgcatctgtaggagacagagtcacagagcattggcggctatttaaattggtatcagcagaaacctgatctatactgcatccagtttgcaaagtggggtcccattctgggacagatttcactctcagcatcagcagtctgcaactactgtcaacagagttacactacccctaggacgttcggccaaacgaactgtggctgcaccSequenceID226Serccatcacttgccgggcaagt60cagggaaagcccctaacctc120caaggttcagtggcagtgga180ctgaagattttgcaacttac240aagggaccaaggtggaaatc300320Ser1CysLysGinPhe65TyrLysProSerSerArgAlaProSer50ThrCysValGly35GlySer20LysLeu5GinAlaProValProSerLeuSerlieAlaSerlieGlyAsnSerValGlyAsp10GinGluGinSer85LysSer70TyrArgArg55SerThrThrLeu40PheGly25LeuTyrlieGlyLeuGinProArgValThrLeuAsnTrpSerThrValProAla105Arg90AlaTyrSerGlu75ThrThrGly60AspPheAla45SerPheGlyTyr30SerGlyAlaGinlie15GinThrGinSerLeuThrThrGly95AspTyr80Thrlie100SequenceID227tctccatcctccctgtctgcatctgtaggagacacagtcaccatcacttgccgggcaagt60106[3094]cagaacatttactactatttatattggtatcagcagaaaccaggaaaagcccctaatctc120[3095]ctgatatatggtgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtggt180[3096]tctgggacagatttcactctcaccatcagcagtctacaacctgaagattttgcaacttac240[3097]tactgtcaacagacttacgacacgcctcccactttcggccctgggaccaaagttgatatc300[3098]aaacgaactgtggctgcacc320[3099]SequenceID228[3100]SerProSerSerLeuSerAlaSerValGlyAspThrValThrlieThr[3101]151015[3102]CysArgAlaSerGinAsnlieTyrTyrTyrLeuTyrTrpTyrGinGin[3103]202530[3104]LysProGlyLysAlaProAsnLeuLeulieTyrGlyAlaSerSerLeu[3105]354045[3106]GinSerGlyValProSerArgPheSerGlySerGlySerGlyThrAsp[3107]505560[3108]PheThrLeuThrlieSerSerLeuGinProGluAspPheAlaThrTyr[3109]65707580[3110]TyrCysGinGinThrTyrAspThrProProThrPheGlyProGlyThr[3111]859095[3112]LysValAsplieLysArgThrValAlaAla[3113]100105[3114]SequenceID229[3115]tctccttccaccctgtctgcatttgtaggagacagagtcaccatcacttgccgggccagt60[3116]caaagtattagtacctggttggcctggtatcagcaaaaaccagggaaagcccctaacctc120[3117]ctgatctataaggcgtctaatttagaaagtggggtcccatcaaggttcagcggcagtgga180[3118]tctgggacagagttcactctcaccatcagcagcctgcagcctgatgattttgcaacttat240[3119]tactgccagcagtttagaagtcattcgtacacttttggccaggggaccaagttagagatc300[3120]aaacgaactgtggctgcacc320[3121]SequenceID230[3122]SerProSerThrLeuSerAlaPheValGlyAspArgValThrlieThr[3123]151015[3124]CysArgAlaSerGinSerlieSerThrTrpLeuAlaTrpTyrGinGin[3125]202530[3126]LysProGlyLysAlaProAsnLeuLeulieTyrLysAlaSerAsnLeu[3127]354045[3128]GluSerGlyValProSerArgPheSerGlySerGlySerGlyThrGlu[3129]505560[3130]PheThrLeuThrlieSerSerLeuGinProAspAspPheAlaThrTyr[3131]65707580[3132]TyrCysGlnGinPheArgSerHisSerTyrThrPheGlyGinGlyThr3133]3134]3135]3136]3137]3138]3139]3140]3141]3142]3143]3144]3145]3146]3147]3148]3149]3150]3151]3152]3153]3154]3155]3156]3157]3158]3159]3160]3161]3162]3163]3164]3165]3166]3167]3168]3169]3170]3171]8590LysLeuGlulieLysArgThrValAlaAla100105SequenceID231tctccctccaccctgtctgcatctgtaggagacagagtcacagagtagtagtaactggttggcctggtatcagcagaaacctgatctataaggcgtctaatttagaaagtggggtcccattctgggacagaattcactctcaccatcagcagcctgcagctactgccaacagtccgtgacgttcggccaagggaccaagggctgcacc232SerAlaSerValGlyAsp95ccatcacttgccgggccagtctgggaaaggccccaaactccaaggttcagcggcagtggactgatgattttgcaacttactggaaatcaaacgaactgtgSequenceIDSerProSerThr1CysArgAlaLeu5GinSer20LysGlyProLysLysProGly35GlyValProSerSerSerSerAsn25LeuGluSer50ThrLeuThrlieLeu40PheArgValThrLeuAlaTrplieTyrLys10TrpPhe65TyrCysGinGinLysArgThrArg55SerLeuGinProAla45SerTyr30Serlie15GinThrGinSer85AlaAlaSer70ValThrPheGlySerGlySerGly60AspPheGin90Asp75GlyGlyAlaThrLysValAsnLeuThrGluThrGlu95Tyr80lieVal100SequenceID233tctccctccaccctgtctgcatctgtaggagacagagtcacagagtagtagtaactggttggcctggtatcagcagaaacctgatctataaggcgtctaatttagaaagtggggtcccattctgggacagaattcactctcaccatcagcagcctgcagctactgccaacagtccgtgacgttcggccaagggaccaagggctgcaccSequenceID234SerProSerThrLeuSerAlaSerValGlyAsp1510CysArgAlaSerGinSerSerSerAsnTrpLeu2025LysProGlyLysGlyProLysLeuLeulieTyr3540ccatcacttgccgggccagtctgggaaaggccccaaactccaaggttcagcggcagtggactgatgattttgcaacttactggaatcaggacgaactgtgArgValThrlieThr15AlaTrpTyrGinGin30LysAlaSerAsnLeu4560120180240300308601201802403003083172]3173]3174]3175]3176]3177]3178]3179]3180]3181]3182]3183]3184]3185]3186]3187]3188]3189]3190]3191]3192]3193]3194]3195]3196]3197]3198]3199]3200]3201]3202]3203]3204]3205]3206]3207]3208]3209]3210]GluSerGlyValProSerArgPheSerGlySer5055PheThrLeuThrlieSerSerLeuGinProAsp657075TyrCysGinGinSerValThrPheGlyGinGly8590GlyArgThrValAlaAla100SequenceID235tctccatcctcactgtctgcatctgtaggagacagagtcacagggtattggcagctggttagcctggtatcagcagaaacctgatctatgctgcgtccactttgcaaagtggggtcccattctgggacagatttcactctcaccatcaccagcctgcagctactgccaacagtataatagttacccgtacacttttggccaaacgaactgtggctgcaccSequenceID236SerAlaSerValGlySerGlyThrGlu60AspPheAlaThrTyr80ThrLysValGluSer95ccatcacttgtcgggcgagtcagagaaagcccctaagtcccaaggttcagcggcggtgggctgaagattttgcaacttataggggaccaagctggagatcSerProSerSer1CysArgAlaLeu5GinGlylieGlySer20LysAlaProLysLysProGlu35GlyValProSerGinSer50ThrLeuThrlieSer40PheSer25LeuGlyAsp10TrpLeulieTyrSerGlyGlyPhe65TyrCysGinGinArg55SerLeuGinProThr70AsnSerTyrProArgAlaAlaGly60AspValThrTrpTyr85LysArgThrValAla105Tyr90AlaGlu75ThrPheAla45SerPheGlyTyr30SerGlyAlaGinlie15GinThrThrThrGly95ThrGinLeuAspTyr80ThrLysLeuGlulie100SequenceID237tctccacccaccctgtctttgtctccaggggacagagccagagagtattggcaggcgcttagcctggtaccaacagaaacctcatccatgatgcatctcacagggccagtggcatcccactctggcacagacttcactctcaccatcagcagcctagagctactgtcaacagctcacaacctggtcgtacacttttggccagacgaactgtggctgcaccSequenceID238SerProProThrLeuSerLeuSerProGlyAsp60120180240300320ccctctcttgcagggccagt60ctggccaggctcccaggctc120ccaggttcagtggcagtggg180ctgacgattttgcaatttat240aggggaccaaggtggagatc300320ArgAlaThrLeuSer1CysArgAlaLysProAlaPhe65TyrSer50ThrGly35GlySer20Gin5GluSerlieGlyAlaProArgCysLysVallieProProLeuThrlieGinLeu40PheArg25Leu10ArgLeulieSerGlySerAlaTrpHisAspGinGluLeu85ArgSer70ThrArg55SerLeuGluProGly60AspThrArgThrTrpSerValTyr90AlaAsp75ThrPheAla45SerPheGlyTyr30SerGlyAlaGin15GinGinHisArgAspSer1CysArgHisLysArgAla50AspPhe65TyrTyrGlyThrProGlyThrAlaPro35ThrSer20GlyLeu5GinAsnlielieGinProProGlylieProThrLeuThrArg40ArgSer25LeuGly10SerCysGinLysHis85Glulie70TyrAsp55SerArgLeuGluGlySerSerlieLysGlyThrlieGly95Tyr80ThrlieArgArgThrValAla100105SequenceID239tctccaggcaccctgtctttgtctccaggggaaagagccacagaatattatcagcagttacataacttggtaccagcacactcctcatctatggtgcatctagcagggccactggcatccgggtctgggacagacttcactctcaccatcagcagactggtattactgtcaacactatggtagttcacttccgtacccctgagatcaaaggaactgtggctgcaccSequenceID240SerLeuSerProccctctcctgcagggccagt60aacctggccagcctcccagg120cagacagattcagtggcagt180agcctgaagattttgcagta240ttgggcaggggaccaagctg300326GluTyrLeuliePheSerGlyArglieTyrAlaThrThrGly45GlyTrp30AlaLeuSer15TyrGinSerSerPro75ProSer60GluAspLeu90ValAlaLeuGlulieLysGlyThr100105SequenceID241tctccaggcaccctgtctttgtctccaggggaaagagccacagagtgttagcagcacctacttagcctggtaccagcagactcctcatctatggtgcatccaacagggccactggcatccTyrAlaPheProPheSerGlyThrAlaGly95Val80Ginccctctcctgcagggccagtaacctggccaggctcccaggcagacaggttcagtggcagt60120180gggtctgggacagacttcactctcaccatcagcagactggtattactgtcagcaatatggtagctcaccggccactttcgatcaaacgaactgtggctgcaccSequenceID242SerLeuagcctgaagattttgcagtggcggagggaccaaggtggagSer1CysGinArgAsp65TyrProArgLysAla50PheGlyThrAlaTyrThrLysPro35ThrThrCysValSer20GlyGlyLeuGinLeu5GinGinlieThrSerAlaProlie70TyrGin85lieLysValProAsp55SerGlyArgSerProSerArg40ArgArgSerThrSer25LeuPheLeuSerGly10ThrLeuSerGluGluTyrlieGlyArgLeuTyrSer60GluAlaThrAlaPro90AlaAlaPro75AlaThrGly45GlyAspPheTrp30AlaSerPheGlyLeu15TyrSerGlyAlaGly95SerGinAsnThrVal80GlyGlulieLysArgThrVal100105SequenceID243tctccaggcaccctatctttgtctccaggggaaagaaccacagagtgttaggggcacctacatagcctggtaccagcagactcctcatctatggtgcatccagcagggccactggcatccgggtctgggacagacttcactctcaccgtcagcagactggtattactgtcagcagtatggtagctcaccgtggacgttcgatcaaacgaactgtggctgcaccSequenceID244SerSer1CysGinArgAsp65TyrProArgArgAla50PheGlyThrAlaTyrThrLysPro35ThrThrCysValSer20GlyGlyLeuGinGluLeu5GinGinlieThrSerAlaProVal70TyrGin85lieLysLeuValProAsp55SerGlyArgSerProArgArg40ArgArgSerThrGly25LeuPheLeuSerValGly10ThrLeuSerGluGluTyrlieGlyArglieTyrSer60GluThrThrAlaPro90AlaAlaPro75TrpThrGly45GlyAspPheTrp30AlaSerPheGlyLeu15TyrSerGlyAlaGin95SerGinSerThrVal80Gly240300323ccctctcctgcagggccagt60gacctggccaggctcccagg120cagacaggttcagtggcagt180agcctgaagattttgcagtg240gccaagggaccaaggtggaa300323111100105SequenceID245tctccaaactccctggctgtgtctctgggcgagagggccacagagtgttttatacagctccaacaataagaacttcttagggacagcctcctaagctgctcttttactgggcatctaccccgattcagtggcagcgggtctgggacagatttcactctcagaagatgtggcaatttattactgtcagcagtatcacagtagggaccaaggtggagatcaaacgaactgtggctgcaccSequenceID246AlaValSerLeuGlyGluccatcaactgcaagtccagccttggtaccagcagagaccagggaatccggggtccctgacccatcagcagcctgcaggctctcctccgacgttcggccaaSerProAsnSerLeu15CysLysSerSerGinLeuAlaTrp35AlaSer20TyrGinGinArg10SerArgSerAsnSerValLeuTyr25GlyGinProProAlaThrAsnTyrTrp50GlyPro40SerGlyValProSer65GluAspValAlaSerThrArgGluSerGlyValProAsp5560PheThrLeuThrlieSerLys45ArgLys30Leulie15AsnAsnPheLeuPhePheSerGlySerGlyThrAsp70lieTyrTyr85GlyThrLysVallie75TyrHisSerThrCysGinGin90lieLysArgThrSerLeuGinAla80ProThrPheGlyGinGlyThrLysValGlu100105SequenceID247tctccaaactccctggctgtgtctctgggcgagagggccacagagtgttttatacagctccaacaataagaacttcttagggacagcctcctaagctgctcttttactgggcatctaccccgattcagtggcagcgggtctgggacagatttcactctcagaagatgtggcaatttattactgtcagcagtatctcagtagggaccaaggtggagatcaaacgaactgtggctgcaccSequenceID248AlaValSerLeuGlyGluVal110Pro95AlaAlaccatcaactgcaagtccagccttggtaccagcagagaccagggaatccggggtccctgacccatcagcagcctgcaggctctcctccgacgttcggccaaSerProAsnSerLeu15CysLysSerSerGinLeuAlaTrp35TyrTrpAla50Ser20TyrGinGinArg10SerArgSerAsnSerValLeuTyr25GlyGinProProAlaThrAsnSerThrArgGlu55Pro40SerGlyValProAsp60Lys45ArgLys30Leulie15AsnAsnPheLeuPhePheSerGly6012018024030033860120180240300338[3328]SerGlySerGlyThrAspPheThrLeuThrlieSerSerLeuGinAla[3329]65707580[3330]GluAspValAlalieTyrTyrCysGinGinTyrLeuSerThrProPro[3331]859095[3332]ThrPheGlyGinGlyThrLysValGlulieLysArgThrValAlaAla[3333]100105110[3334]Sequence；ID249[3335]tctccagactccctggctgtgtctctgggc:gagagggccaccatcaactgcaagtccagc60[3336]cagagtgttttacacagctccaacaataagaactacttagcttggtaccagcagaaacca120[3337]ggacagcctc丨ctaagctgctcatttactgggcatctatccgggaatccggggtccctgag180[3338]cgattcagtg;gcagcgggtctgggacagatttcactctcaccatcagcagcctgcaggct240[3339]gaagatgtgg丨cagtttattactgtcagcaatattatagttctcctctcactttcggcgga300[3340]gggaccaaggtggagatcaaacgaactgtggctgcacc338[3341]Sequence！ID250[3342]SerProAspSerLeuAlaValSerLeuGlyGluArgAlaThrlieAsn[3343]151015[3344]CysLysSerSerGinSerValLeuHisSerSerAsnAsnLysAsnTyr[3345]202530[3346]LeuAlaTrpTyrGinGinLysProGlyGinProProLysLeuLeulie[3347]354045[3348]TyrTrpAlaSerlieArgGluSerGlyValProGluArgPheSerGly[3349]505560[3350]SerGlySerGlyThrAspPheThrLeuThrlieSerSerLeuGinAla[3351]65707580[3352]GluAspValAlaValTyrTyrCysGinGinTyrTyrSerSerProLeu[3353]859095[3354]ThrPheGlyGlyGlyThrLysValGlulieLysArgThrValAlaAla[3355]100105110[3356]Sequence；ID251[3357]tctccagactccctggctgtgtctctgggc:gagagggccaccatcaactgcaagtccagc60[3358]cagagtgttttatacagctccaacaataagaactacttagcttggtaccagcagaaacca120[3359]ggacagcctc丨ctaagctgctcatttactgggcatctacccgggaatccggggtccctgac180[3360]cgattcagtg;gcagcgggtctgggacagatttcactctcaccatcagcagcctgcaggct240[3361]gaagatgtgg丨cagtttattactgtcagcaatattatagtactccgacgttcggccaaggg300[3362]accaaggtgg；aaatcaaacgaactgtggctgcacc335[3363]Sequence；ID252[3364]SerProAspSerLeuAlaValSerLeuGlyGluArgAlaThrlieAsn[3365]151015[3366]CysLysSerSerGinSerValLeuTyrSerSerAsnAsnLysAsnTyrLeuAlaTrp35TyrTrpAla50SerGlySer65Glu20TyrGinSerThrThrGinLysArgAspPheGlyValGinGlyAlaAsp70ValTyr85ThrLysGlu55PheTyrValPro40SerThrCysGinGlu25GlyGinProProGlyValProLeuThrlie75TyrAsp60SerLys45Arg30LeuLeuliePheSerGlyGlyThrLysValGlulie100105SequenceID253ctcgagtctggggccgaggtgaagaagcctggggcctcagtctggatacaccttcggcgaccactatatgcactgggtgccctgagtggttgggaataatcaaccctaggagcggtaggacagggcagagtcaccatgaccagcgacacgtccacgagcaggcctgagatttgatgacacggccatgtatttctgtggaacggtcagtcatcacaccccaagattggttcgacccctggggtctccttggcctccaccaagggcccatcggtcttcccccacctctgggggcacagcggccctggSequenceID254GluValGin90LysArgThrValSerLeuGinAla80ThrTyrSerThrThrValAla110Pro95Alatgaaggtttcgtgcacgaca60ggcaggcccctggacaaagg120caacctacgcacagaagttc180cgttctacatggagctgagc240gagatgttagacgggcgcct300gccagggaaccctggtcacc360tggcaccctcctccaagagc420445LeuGluSerGlyAla15SerCysThrThrSerCysValArgProArg50ThrMet65GlyLeuThrThr20GinAlaPro35SerGlyArgSerAspArgTrpProArgGlySer130ThrArgPheAlaPro100GlyAsp85ArgGlyGlyThrThr70AspTyrGinThr55SerLysLysThrPhe25ProPro10GlyArg40TyrAlaThrSerValThrLeuValThrAlaMetlieGluGinSerThrGlyAlaSerValAspHisTyrTrpLeuLysGly45GinMet30liePhe75PhePhe60TyrMetLys15HislieArgGin115ValPheProLeuAla135Thr120ProThr105ValTyr90ProGinCysAspSerLeuAlaSerSerLysSer140GlyTrpSer125ThrGlyGluLeuArgPhe110ThrAsp95AspLysSerGlyValTrpAsnValSer80ValProGlyGlyThrAlaAlaLeu145SequenceID255ctcgagtctgggggaggcttggtcaagcctggagggtccctgagactctcctgtgcagcc60[3410]tctggattcagcttcagtgactactacatgacctggatccgccaggctccagggaagggg120[3411]ctggagtggctttcatacattagtggtagtggtcgcaccatatactacgcagactctgtg180[3412]aagggccgattcaccatctccagggacgacgccaagaactccctgtatctgcaaatgaac240[3413]agcctgagagccgaggacacggccgtgtattactgtgcgagagattccccaacgaggacg300[3414]tattccgattttaggggtggtcccaaccagcccgaatactactactacggtatggacgtc360[3415]tggggccaagggaccacggtcaccgtctcctcagcctccaccaagggcccatcggtcttc420[3416]cccctggcaccctcctccaagagca445SequenceIDLeuGluSer1SerCysAla256GlyAla20AlaGly5SerlieArgGin35GlyArgThrlieGlyLeuValLysGlyPheSerProGlyLysPhe25LeuPro10SerGlyGlyAspTyrGluTrpLeuSerLeuTyrGlySer50lieGly40TyrAlaAspSerThr65SerLeuArgAlaTyr55AlaLysAsnSerSerArgAspAsp70AspThrAlaValGlu85TyrSerAspPheLeu75TyrVal60TyrProThrArgThr100TyrGlyMetAspTyrTyrTyr115ValSerSerAlaSerThr130SerSerLysSer145SequenceID257Arg105TrpTyr90GlyGlyCysProGlyGinGlySer45LysLeuAlaAsnLys135Val120GlyProSerValMet30TyrGlyGinArgGin110ThrPhe140Thr125ProLeuArg15ThrlieArgMetAsp95ProValAlaLeuTrpSerPheAsn80SerGluThrProggggaggcttggtgaagcctggagggtccctgagactctcctgtggagcc60ggttcagtgactaccacatgagttggatccgccaggctccagggaagggc120tctcacacattagtggtagtggcgtttccaaatactacgcagactctgtg180tcaccatctccagggacaacgccaagaattcactgtatctacaaatggac240acgaggacacggccgtatattactgtgcgagagagtcgtggctggcaata300gccagggaaccctggtcaccgtctcctcagcctccaccaagggcccatcg360115gtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaacSequenceID258GlyLeuLeu1SerlieGlyGluSerGlyGly5SerCysArgSer50lieGlyAla20AlaProGin35GlyThr65SerLeuArgTrpLeuAlaValSerArgAspAspGlyGlyLysSerLysValLysPheArgTyr55AlaGly40TyrPhe25LeuPro10SerGlyAspTrplie100ThrSerAlaSer115LysSerThrSer130TyrPheProGlu145SequenceID259Glu85AspLysGlyAsn70AspThrLysAlaHisTrpGlyAlaAsnSerValTyr90GlyGluAspSerGlySerLeuTyrHisValSer45ValLys60TyrLeuMet30HisLeu75TyrCysAlaThrLeuValGlyGinMetArgArgLeu15SerTrplieSerArglieGlyProGlyThr135Gin105ValPheProLeuSer120AlaAlaLeuGlyThr110ProGlu95ValAsp80SerSerSerSerCys140Ala125LeuValLysAspSequenceID260LeuGluSerGlyGlyAsnLeuAlaGinProGly1510SerCysAlaAlaSerGlyPheMetPheGlyAsn2025ValArgGinAlaProGlyLysGlyLeuGluTrp3540GlySerLeuArgVal15TyrAspMetPheTrp30ValSerGlylieAsp45420445ctcgagtcggggggaaacttggcacagccgggggggtccctgagagtctcctgtgcagcc60[3470]tccggattcatgttcgggaattatgacatgttttgggtccgccaggctccagggaagggg120[3471]ctggagtgggtctcagggatcgatggtcgcagtgagaagacatactacgcagactccgtg180[3472]aagggccggttcagcgtctccagagacaattccaagaacacactgtatttacaattgaac240[3473]agactgagagccgaagacacggccgtttattactgtgcgaaacccccggacagtgggagc300[3474]cccatctattttgacaactggggccagggaaccctggtcaccgtctcgtcagcctccacc360[3475]aagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcg420[3476]gccctgggctgcctggtcaaggact445116GlyArg50ValSer65ArgAspValAlaLeuSerThrPro130ValSerSerArgGlyVal115SerGluArgAlaSer100SerLysThrAspSerLysAspGlu85ProSerLysAsn70AsplieAlaSerTyr55SerThrTyrSerThr135TyrLysAlaPheAlaAsnValAsp105LysThr120SerGlyAspThrTyr90AsnGlyGlySerVal60TyrLeu75TyrTrpProThrCysGlySerAla140LysLeuAlaGinGlyGinLysGly110PheArgPheLeuVal125AlaLeuPro95ThrProGlyAsn80ProLeuLeuCysLeu145SequenceID261ctcgagtcggggggaggcgtggtccggcccgggacgtccctgacactctcctgtgcagcc60[3500]tctggattcgtcttcacaacttatggcatgcactgggtccgccaggctccagggaagggg120[3501]ccggagtgggtggcagtcatttcaaccgatggaaataaaaaagcctatggcaactccgtg180[3502]aagggccgattcaccatctccagagacagattcagcaacacggtgtctttgcaaatggac240[3503]agcctgagaccagatgacacggctatttattactgcgcgaaggaagggctgcgtgggact300[3504]tacgttcgaggtgacctccagcattggggccagggcaccctggtcgtcgtctcttcggcc360[3505]tccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggc420[3506]acagcggccctgggctgcctggtca445SequenceIDLeu1SerValThrThr65SerLeuThrGluCysArgAsp50lieLeuArgLeuSerAlaGin35GlySerArgGlyVal262GlyAla20AlaAsnArgProGly5SerProLysAspAsp85ThrTyr100ValValGlyGlyGlyLysArg70AspValSerValPheLysAla55PheThrArgSerValArgValGly40TyrSerAlaGlyAlaPhe25ProGlyAsnlieAsp105SerPro10ThrGluAsnThrTyr90LeuGlyThrTrpSerVal75TyrGinThrLysThrTyrValVal60SerCysHisGlySerGlyAla45LysLeuAlaTrpProLeuThr15HisMet30ValGlyGinLyslieArgMetGlu95GinGly110SerValLeuTrpSerPheAsp80GlyGlyPhe117[3523]115120ProLeuAlaProSerSerLysSerThrSerGly130GlyCysLeuVal145SequenceID263135125GlyThrAlaAlaLeu140ctcgaggagtctgggggaggcgtggtccagcctggggggtccctgagactctcctgtgca60[3530]gcctctggattttccttcagtaactatggcatgcactgggtccgccaggctccaggcaag120[3531]gggctggagtgggtaactcttatatcagatgatggaagtaataaattctatgcagactcc180[3532]gtgaagggccgattcaccatctccagagacaattccaaaaacacgttgtatgtgcaaatg240[3533]aacagcctgagacctgaagacacggctatatactactgtgcgaaagggtcccgtgatctc300[3534]agtggttactattcgccggactactggggccagggaaccctggtcaccgtctcctcagcc360[3535]tccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggc420[3536]acagcggccctgggctgcctggtca445SequenceIDLeuGluGlu1LeuSerCys264SerAla20GinGlyGly5AlaSerGlyGlyAlaProGlyValValPheTrpValArg35AspGlySerAsnSerAsp50ThrPhe65AsnlieSerArgAsp70GluLys55AsnLys40PheSer25GlyLeuGinPro10PheSerSerLeuArgPro85SerSerArgAspAspGlyTyrTyrTyrSerLysThrAlaLeu100ThrValSerSerThrLeuVal115ProLeuAlaProSerSer130CysLeuValLys135Ala120SerSer105SerAlaAsnlie90ProGluAspThr75TyrAspThrLysThrSerGlyGlyAsnTrpSer60LeuTyrTyrGlyGly140GlySerTyrVal45ValTyrCysTrpPro125ThrGly30ThrLeuLeuArg15MetHisLysValAlaGly110SerGlyGinLys95GinlieArgMet80GlyGlyPheValAlaAlaLeuGly145SequenceID265ctcgaggagtctgggggaggcgtggtccagcctgggaggtgcctctggattccccttcagtagttatggcatgcactggggggctggagtgggtggcaggtgtttcatatgatggaagttccctgagactctcctgtgcatccgccaggctccaggcaagataaatactatgcggactcc60120180gtcaagggccgattcaccatctccagagacagttccaagaaacagcctgagacctgaggacacggctgtgtattactgtgggaatatacattattctaaacggtttggacgtctggggcctcttcagcctccaccaagggcccatcggacttccccctggtctggrggcacagcggccctgggctSequenceID266LeuGluGluSergcactctatatctgcaaatgcgagaccttccgcgatttttaagggaccacggtcaccgycmaccctcctccaagagcacc1LeuSerCysAla20GinGlyGlyGlyValVal5AlaSerGlyGlyAlaProGlyTrpValArg35AspGlySerTyrPhePro25GlyGinPro10PheSerGlySerLeuGluTrpArgSerTyrSerTyr50PheThr65AsnSerLeuArgLys55SerLys40TyrTyrAlaAsplieSerArgAsp70GluAspThrAlaPro85GlySerLysSerThr75TyrSer60LeulieTyrlieSerAlaliePhe100GlyGinGlyThrThrValThr115Val120lie105SerVal90LeuAsnTyrGlySerAlaSerVal45ValTyrCysLeuThr125Gly30AlaLysLeuAlaLeu15MetGlyGlyGinArgHisValArgMet80ProArg95AspValTrp110LysGlyProSequenceID268LeuGluSerGlyGlyGlyLeuValGinProGly1510SerCysAlaAlaSerGlyPheSerValSerSerGlySerLeuArgLeu15lieTyrMetSerTrp240300360420445SerAspPheProLeuAlaProSerSerLysSerThrSerGlyGlyThr[3585]130135140[3586]AlaAlaLeuGly[3587]145[3588]SequenceID267[3589]ctcgagtctgggggaggcttggtccagcctggggggtccctgagactctcctgtgcagcc60[3590]tctggattcagcgtcagtagcatctatatgagctgggtccgccaggctccagggaagggg120[3591]ctggagtgggtctcacttatttatgacggtggtagcacatactacgcagactccgtgaag180[3592]ggccgattcaccgtctccagggacaattccaagaacacgctctatcttcaaatgaacagc240[3593]ctgagaggtgaagacacggctatatattactgtgcgagaggggtcgaggactattacact300[3594]gataccagtggtttttacctgggttttgcctactggggccagggaaccccggtcaccgtc360[3595]tcctcagcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacc420[3596]tctgggggcacagcggccctgggct445ValArgAspVal65LeuAspGlyGly50SerArgTyrGinGin35GlySer20AlaProArgGlyTyrGly115PheAspGluThrAsnAsp85AspGlyLysTyrSer70ThrTyr55LysGly40Ala25LeuGluThr100ThrProSerVal130AlaAlaLeuGly145SequenceID269ThrValThrProLeuAlaAsnAlalieSerGlyAspThrLeuTyrTrpValSerValPro135Val120SerPhe105SerTyr90TyrTyr75CysLys60LeuSer45GlyAlaLeuGlyGinArgGlyPheAla110Lys30LeulieArgPheMetAsnTyrThrSer80GluVal95TyrTrpSerLysSerThr140SerAlaSerThrLysGly125SerGlyGlyThrProctcgagcagtctgggggaggcttggtccaaccgggggggtccctgagactctcctgtgca60[3620]ggctctggattcagtttcaaaagttatttcatgagttgggtccgccaggctccagggaag120[3621]gggctggagtgggtggccaacataaagcaatatggaggcgacaaatactatgcggactct180[3622]gtgaaaggacgattcaccatctccagagacgacgccaagaatttagtgtatctggaaatg240[3623]aagagcctgagagccgacgacacggccgtgtattactgtgcgagaggatccctagaggga300[3624]ttttttgagttcggtcagttaagtccgggatggttcgacttctggggccagggaaccctg360[3625]gtcaccgtctcctcagcctccaccaagggcccatcggtcttccccctggcaccctcctcc420[3626]aagagcacctctgggggcacagcgg445SequenceIDLeuGluGin1LeuSerCysTrpLysPhe65Lys270SerAla20GinGlyGly5GlySerValArg35TyrGlyGlyAspGin50ThrAlaGlylieSerArgGlyLeuValGlyPheProGlyLys55AspSerLeuArgAla85Asp70AspAspLys40TyrAlaThrSer25GlyLeuGinProGly10PheTyrLysAlaAlaAsnVal90LysGluTrpAspSer60LeuVal75TyrTyrGlySerSerTyrVal45ValPhe30AlaLeuArg15MetSerTyrCysAlaAsnLysGlyLeuGluArg95lieArgMet80GlySerLeuGluGlyPhePheGluPheGlyGinLeu100105AspPheTrpGlyGinGlyThrLeuValThrVal115120LysGlyProSerValPheProLeuAlaProSer130GlyGlyThrAla145SequenceID271135SerProGlyTrpPhe110SerSerAlaSerThr125SerLysSerThrSer140ctcgagtcgggcccaggactggtgaagccttcacagaccctgtccctcacctgcgttgtc60[3650]tctggtgactccatggataggggtggatacgcttggagctggaaccggcagccaccaggg120[3651]aagggactggagtggattgggtatatctattacagagggaccacctactacagcccgtcc180[3652]ctcaagagtcgagtcaccatgtctttagacacgtccaacaaccagatctccctgaaactg240[3653]agctctgtgaccgccgcggacacggccgtctattattgtgccagagtaccactcctaaat300[3654]tacgatattttgactggttattatactgtgaatgcttttgatgtctggggccaagggaca360[3655]atggtcaccgtctcttcagcctccaccaagggcccatcggtcttccccctggcaccctcc420[3656]tccaagagcacctctgggggcacag445SequenceIDLeu1ThrSerlieVal65SerProPheThrGluCysTrpTyr50ThrSerLeuAspSerValAsn35TyrMetValLeuVal115GlyLys130SerGlyGly145SequenceID272GlyVal20ArgArgSerThrAsn100TrpProThr273Pro5SerGinGlyLeuAla85TyrGlySerGlyGlyProThrAsp70AlaAspGinValLeuAspProThr55ThrAsplieGlyPhe135ValLysSerGly40TyrSerThrLeuMet25LysTyrAsnAlaThr105MetThr120ProLeuPro10AspGlySerAsnVal90GlyValAlaSerArgLeuProGin75TyrTyrThrProGinGlyGluSer60lieTyrTyrValSer140ThrLeuGlyTrp45LeuSerCysThrSer125SerTyr30lieLysLeuAlaVal110SerAlaLysSerSer15AlaGlySerLysArg95AshLeuTrpTyrArgLeu80ValAlaSerThr1213679]3680]3681]3682]3683]3684]3685]3686]3687]3688]3689]3690]3691]3692]3693]3694]3695]3696]3697]3698]3699]3700]3701]3702]3703]3704]3705]3706]3707]3708]ctcgagtcgggcccaggactggtgaagccttcgcagaccctgtccctcacctgcgctgtctctggtggctccatcagcagtgaaggtttctcctggagttggatccggcagccaccagggaagggactggagttcattggttatatttattacaatgggaggacctatttcaacccgtccctcaggagtcgagttagcatttccgcagacatgtccaagaaccaattttccctgaaactgccctctgtgaccgccgcggacacggccgtctatttctgtgccagtacaataggatacacctatggcccggaatacttccatcactggggccagggcacccgggtcaccgtctcctcagcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctggtcaSequenceID274GlyLeuValLysLeuGluSerGly1ThrCysSerTrpPro5SerGlyGlySerAlaVal20ArgGinProProlieVal65ProTyr50Serlie35TyrAsnGlyArglie25LysSerGinSerGluGlyLeuGluPro10SerThrLeuGlyThr55MetGly40TyrPheAsnProlieSerAlaAsp70AlaAspThrAlaSer60PhePhe45LeuPhe30lieSerLeu15SerTrpGlyTyrArgSerArgSerLysAsnGin75TyrPheSerLeuLysSerValThrAlaAlaAspThrAlaVal8590TyrGlyProGluTyrPhelieGlyTyrThrArgThr100ThrValSerSerVal115AlaProSerSerTyr105SerThrLysGlyCysAlaHisHisTrpProLeu130GlyCysLeuVal145SequenceID275Lys135Ala120SerThrSerLysGlyGly140Pro125ThrGly110SerSer95GinLeu80ThrGlyPheValAlaAlaLeu601201802403003604204453709]ctcgagtcgggcccaggactggtgaagccttcggagaccctgtccctcacctgcactgtc603710]tctggtggctccgtcaccagtagtagttatctctggggctggatccgccagcccccaggg1203711]aaggggctggactggattgggagtagtcattatagtgggagcacctaccacaacccgtcc1803712]ctcaagagtcgagtcaccacatccgtagacacgtccaagaaccggttctccctgaagctg2403713]agctctgtgaccgccgcagacacggctgtatattactgtgcgagacatgttgagggtgac3003714]tacggtgacttttttgaccactggggccagggaaccctggtcaccgtctcctcagcctcc3603715]accaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacg4203716]gcggccctgggctgcctggtcaagg4453717]SequenceID2763718]3719]3720]3721]3722]3723]3724]3725]3726]3727]3728]3729]3730]3731]3732]3733]3747]3748]3749]3750]3751]3752]3753]3754]3755]3756]Leu1ThrGlySerVal65SerSerValGluLeuValGluCysTrpHis50ThrSerGlyThrlie35TyrThrValGlyThr115Val20ArgSerSerThrAsp100ValPro5SerGinGlyValGlyGlyProSerAsp70AlaLeuGlyProThr55ThrValLysSerAla85TyrGlyAspAspSerSerAlaGly40TyrSerThrPheSer120Val25LysHisLysAlaPhe105ThrPro10ThrGlyAsnAsnSerSerLeuProArg75TyrGluSerAspSer60PheThrLeuSerVal90AspHisTyrTrpLysGlyProTrp45LeuSerCysGlySer125Tyr30lieLysLeuAlaSer15LeuGlySerLysLeuTrpSerArgLeu80HisArg95GinGlyThr110ValPheProLeuAlaProSerSerLysSerThrSerGlyGlyThrAlaAlaLeuGly[3735]130135140[3736]CysLeuValLys[3737]145[3738]SequenceID277[3739]ctcgagtcgggcccaggactggtgaagccttcggagaccctgtccctcacctgcacagtc60[3740]tctgctggctccatcagtagcaacagttatcactggggctggatccggcagcccccagga120[3741]aaggggctggaatggattggccatatttattatagtgggtccaccgactacaatccgtcc180[3742]cttcagagtcgagtcaccatatccattgacacgtccatgaatcgcttctccctaagggtg240[3743]aactctgtgaccgccgcagacacggctgtatatttctgtgcgagattctacggtagttca300[3744]tatgactactggggccggggaaccctggtcgccgtctcctcagcctccaccaagggccca360[3745]tcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggc420[3746]tgcctggtcaaggactacttccccg445SequenceIDLeu1ThrGlylieValGluCysTrpTyr50ThrSerThr278GlyVal20Arglie35TyrSerlieSerPro5SerGinGlylieGlyAlaProSerAspLeuGlyProValLysSerGly40AspThr55ThrSerlie25LysTyrMetPro10SerGlyAsnAsnSerSerLeuProArgGluAsnGluSer60PheThrLeuSerTrp45LeuTyr30lieGinSerLeuSer15HisGlySerArgLeuTrpHisArgVal1233757]3758]3759]3760]3761]3762]3763]3781]3782]3783]3784]3785]3786]3787]3788]3789]3790]3791]3792]3793]3794]3795]65Asn70AlaSerValThrAla85TyrAspTyrGlySerSerSerAla115Ser100SerAspThrAlaTyrTrpThrLysGlyPro120Val90GlyArg105SerVal75TyrGlyPheProPheCysAlaThrLeu80ArgPhe95AlaValLeu125Val110AlaProSer3764]SerLysSerThrSerGlyGlyThrAlaAlaLeuGlyCysLeuValLys3765]1301351403766]AspTyrPhePro3767]1453768]SequenceID2793769]ctcgagtcgggcccaggactggtgaagccttcggggaccctgtccctcacctgcgctgtt603770]tctggtggctccatcagcagtagttactggtggaattgggtccgccagccccccgggaag1203771]gggctggagtggattggggaaatctatcatagtggggtcaccaactccaacccgtccctc1803772]aagagtcgagtcaccatatcagtagacaagtcgaacaatcgctttaccctagagttgaac2403773]tctgtgaccgccgcggacacggccgtctattactgtgcgcgagatggaggccggggatat3003774]tgtagtggtaatagctgccactccgggtctctcccccccccctggttcgacccctggggc3603775]cagggaatcctggtcaccgtctcctcagcctccaccaagggcccatcggtcttccccctg4203776]gcaccctcctccaagagcacctctg4453777]SequenceID2803778]LeuGluSerGlyProGlyLeuValLysProSerGlyThrLeuSerLeu3779]1510153780]ThrCysAlaValSerGlyGlySerlieSerSerSerTyrTrpTrpAsnTrpValTyrThr65SerHis50lieArg35Ser20GinProProGlyValGlyArgProProSerAla130GlySerValAlaThrGlyTrp115SerValThrAspLys70AspAsn55SerTyr100PheAla85CysSerAspThrLysGlyThrGlyProTrpLys40SerAsnAlaAsn25GlyLeuGluTrpAsnProSerAsnArgVallie45LysPro135Ser105GlyGin120SerValTyr90CysPhe75TyrCysLeu60ThrLeu30GlyGlulieSerArgValAlaHisSerGlyGluLeuArgAsn80GlyGlylieLeuPheProLeu140Asp95SerLeuPro110ThrValSerVal125AlaProSerSer124LysSerThrSer145SequenceID281ctcgagtcgggcccaggacttctggtgcctccatcagcagaagggactggagtggattggctcaagagtcgagtctccataattctgtgaccgccgcagaatgattcgggggaatgttttgcctccaccaagggcccatcggcacagcggccctgggctgcctgSequenceID282GluSerGlyggtgaagccttcacagaccctgtccctcacctgcactgtctgaaacttactactggagctggatccggcagcccgccggggcgtatgtataccagcgggagtagcaactacaacccctccgtcggtcgacacgtccaagaaccagttctccctgaacctgcacggccgtgtattattgtgcgagagatgtattggtcacttgacatatggggccaagggacagtggtcaccgtctcttcaggtcttccccctggcaccctcctccaagagcacctctgggLeu1ThrCysThrPro5SerVal20ArgGinProAlaGlyLeuValLysGlyAlaSerSerTrplie35ThrSerGlySerlie25LysSerGinSerGluGlyLeuGluPro10SerThrLeuThrMetTyr50SerMetSerValVal65AsnSerValThrSer55ThrGly40AsnTyrAsnProValLeuValGlyThrVal115Ala85MetAsp70AlaAspThrAlaSerLysAsnGin75TyrSer60PheThr100ValThrValSerlieArgGlyAsn105SerAla120Val90ValTyrPheAspSerThrLysTrp45LeuSerCyslieGly125Tyr30lieLysLeuAlaTrp110ProSer15TyrGlySerAsnLeuTrpArgArgLeu80AspArg95GlyGinSerVal60120180240300360420444PheProLeuAlaProSerSerLysSerThrSerGlyGlyThrAlaAla[3825]130135140[3826]LeuGlyCy￡>Leu[3827]145[3828]SequenceID283[3829]ctcgagtcgggcccaggactggtgaagccttctcagaccctgtccctcacctgcactgtc60[3830]tctggtgcctccatcagcagtgaaacttactactggagctggatccggcagcccgccggg120[3831]aagggactggagtggattgggcgtatgtataccagcgggagtagcaactacaacccctcc180[3832]ctcaagagtcgagtctccatgtcggtcgacacgtccaagaaccagttctccctgaacctg240[3833]aattctgtgaccgccgcagacacggccgtgtattattgtgcgagagatgtattggtcact300[3834]atgattcgggggaatgtttttgacatatggggccaagggacagtggtcaccgtctcttca360[3835]gcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctgSequenceID284GlyLeuValLysLeuGluSerGly1ThrCysSerTrpThrVal20ArgPro5SerGlyMetVal65AsnTyr50SerGinSerGlySerMetSerVallie35ThrAlaSerProAlaValGlyThrPheSerValThrLeuValAla85MetAsp70AlaThr100ValThrSer55ThrAspArgGly40Asnlie25LysPro10SerTyrSerLysAlaGlyAsnProAsnSerGinSerGluLeuGluThrLeuThrVal115LeuAlaProSerlieValSerThrGlyAsn105AlaVal90ValGin75TyrPheSerThrPro130LeuGlyCysLeu145SequenceID285Ser135Ser120LysSerThrSerSer60PheTyrAspLysGly140Trp45LeuTyr30lieGlySerLeu15TyrTrpArgLysSerArgSerLeuAsnLeu80AspCyslieGly125GlyAlaArg95GlyGinSerValThrAlaAlaTrp110ProSequenceID286LeuGluSerGlyProGlyGinValLysProSerGinThrLeuSerLeu151015ThrCysThrValSerGlyGlySerlieGlySerGlySerTyrSerTrp202530AsnTrplieArgGinProAlaGlyArgGlyLeuGluTrplieGlyArg354045420444ctcgagtcgggcccaggacaggtgaagccttcacagaccctgtccctcacctgcactgtc60[3860]tctggtggctccatcggcagtggttcttactcctggaactggatccggcagcccgccggg120[3861]aggggactggagtggattgggcgaatctctgacagtgggaacaccaatttcaacccctcc180[3862]ctcaagagtcgagtcaccatgtcagtggacacgtccaagaaccagttcgccctgaaactg240[3863]acctctgtgaccgccgcagacacggccacatatttctgtgcgagagggagaggtattttg300[3864]actggtctctttgactattggggccagggatccctggtctccgtctcctcagcctccacc360[3865]aagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcg420[3866]gccctgggctgcctggtcaaggact445[3874lieSerAspSerGlyAsnThrAsnPheAsnProSerLeuLysSerArg[3875505560[3876ValThrMetSerValAspThrSerLysAsnGinPheAlaLeuLysLeu[387765707580[3878ThrSerValThrAlaAlaAspThrAlaThrTyrPheCysAlaArgGly[3879859095[3880ArgGlylieLeuThrGlyLeuPheAspTyrTrpGlyGinGlySerLeu[3881100105110[3882ValSerValSerSerAlaSerThrLysGlyProSerValPheProLeu[3883115120125[3884AlaProSerSerLysSerThrSerGlyGlyThrAlaAlaLeuGlyCys[3885130135140[3886LeuValLysAsp[3887145[3888SequenceID287[3889ctcgagtcgg^cccaggacaggtgaagccltcacagaccctgtccctcacctgcactgtc60[3890tctggtggctccatcggcagtggttcttactcctggaactggatccggcagcccgccggg120[3891aggggactggagtggattgggcgaatctctgacagtgggaacaccaatttcaacccctcc180[3892ctcaagagtcgagtcaccatgtcagtggacacgtccaagaaccagttcgccctgaaactg240[3893acctctgtgaccgccgcagacacggccacatatttctgtgcgagagggagaggtattttg300[3894actggtctctttgactattggggccagggatccctggtctccgtctcctcagcctccacc360[3895aagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcg420[3896gccctgggctgcctggtcaaggact445[3897SequenceID288[3898LeuGluSerGlyProGlyGinValLysProSerGinThrLeuSerLeu[3899151015[3900ThrCysThrValSerGlyGlySerlieGlySerGlySerTyrSerTrp[3901202530[3902AsnTrplieArgGinProAlaGlyArgGlyLeuGluTrplieGlyArg[3903354045[3904lieSerAspSerGlyAsnThrAsnPheAsnProSerLeuLysSerArg[3905505560[3906ValThrMetSerValAspThrSerLysAsnGinPheAlaLeuLysLeu[390765707580[3908ThrSerValThrAlaAlaAspThrAlaThrTyrPheCysAlaArgGly[3909859095[3910ArgGlylieLeuThrGlyLeuPheAspTyrTrpGlyGinGlySerLeu[3911100105110[3912ValSerValSerSerAlaSerThrLysGlyProSerValPheProLeu[3913]115120125[3914]AlaProSerSerLysSerThrSerGlyGlyThrAlaAlaLeuGlyCys[3915]130135140[3916]LeuValLysAsp[3917]145[3918]SequenceID289[3919]ctcgagtcgggcccaggactggtgaagccttcagagaccctgtccctcacctgcactgtc60[3920]tctggtggctccatcagcagtgggagtgactactggagctggatccggcagcccgccggg120[3921]aaggggctggagtggattgggcgaatctccaccaaagggagcaccagctacaacccctcc180[3922]ctccagagtcgagtcatcatatcactagacacgtccaagaaccagttttccctgaagctg240[3923]aggtctgtgaccgccgcagacacggccctttattactgagcgagagctttcccgccggag300[3924]aaggcagcagctggcactttcgacccttggggtcagggaaccctggtcatcgtctcctca360[3925]gcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctggg420[3926]ggcacagcggccctgggctgcctgg445855243ASequenceIDLeuGluSer290Gly1ThrCysSerTrplieSer50lieThrVal20lieArg35ThrLysPro5SerGlyLeuValLysGlyGinGlySerGlySerProAlaVal65ArgSerlieSerLeuValThrProProGluAsp70AlaAla85AlaAlaLys100ThrLeuVallie115ProLeuAlaProSerSer130CysLeuThr55ThrAspAlaGly40Serlie25LysPro10SerTyrSerLysAlaGlyAsnProAsnSerGluThrLeuSerGlySerLeuGluSer60PheTrp45LeuAsp30lieSerLeu15TyrTrpGlyArgGinSerArgSerLeuLysThrGlyLeu90PheGin75TyrTyrAlaArgValSerSerAla120LysSer135Thr105SerThrLysGlyAspProTrpLysThrSerGlyGly140Pro125ThrGly110SerAla95GinLeu80PheGlyPheValAlaAlaLeuGly145SequenceID291ctcgagtcgggcccaggactggtgaagccttcagagaccctctggtggctccatcagcagtgggagtgactactggagctaaggggctggagtggattgggcgaatctccaccaaagggatgtccctcacctgcactgtcggatccggcagcccgccggggcaccagctacaacccctcc60120180128ctccagagtcgagtcatcatatcactagacacgtccaagaaggtctgtgaccgccgcagacacggccctttattactgtgaaggcagcagctggcactttcgacccttggggtcagggaagcctccaccaagggcccatcggtcttccccctggcaccctggcacagcggccctgggctgcctggSequenceID292GlyLeuValLysaccagttttccctgaagctgcgagagctttcccgccggagccctggtcatcgtctcctcacctccaagagcacctctgggLeuGluSerGly1ThrCysSerTrpPro5SerGlyGlySerThrVal20ArgGinProAlalieSer50lielie35ThrLysGlySerGly40Serlie25LysSerGluSerGlyGlyLeuGluPro10SerThrLeuSerVal65ArgSerValThrThr55ThrSerlieSerLeuAsp70AlaAspThrAlaTyrAsnProLysAsnPheProProGlu100GlyThrLeuVal115Ala85LysAlaAlaAlaGin75TyrSer60PhelieValSerSer120Gly105AlaLeu90ThrPheTyrAspSerThrLysTrp45LeuSerCysProGly125Asp30lieGinLeuAlaTrp110ProSer15TyrGlySerLysLeuTrpArgArgLeu80AlaArg95GlyGinSerValSequenceID294LeuGluSerGlyProGlyLeuValLysProSer1510ThrCysThrValSerGlyGlySerlieSerSerGinThrLeuSerLeu15GlySerAspTyrTrp240300360420445PheProLeuAlaProSerSerLysSerThrSerGlyGlyThrAlaAla[3975]130135140[3976]LeuGlyCysLeu[3977]145[3978]SequenceID293[3979]ctcgagtcgggcccaggactggtgaagccttcacagaccctgtccctcacctgcactgtc60[3980]tctggtggctccatcagcagtggaagtgactactggtcctggatccggcagcccgccggg120[3981]aagggactggagtggattggccgaatctccaccagagggagcaccagctacaacccctcc180[3982]ctccagagtcgagtcaccatttcactagacacgtccaagaaccagttttccctgaagttg240[3983]acctctgtgaccgccgcagacacggccctttatttttgtgcgagagctttcccgccggag300[3984]aaaccagcagctggtactttcgacccctggggccagggaaccctggtcaccgtctcctca360[3985]gcctccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctggg420[3986]ggcacagcggccctgggctgcctgg445129SerTrplieVal65ThrSer50Thr20lieArg35ThrArgGinProAlaGlySerlieSerLeuSerValThrAsp70AlaPheProProGlyThrLeu115Ala85LysProThr55ThrAspAlaGly40Ser25LysTyrSerLysAlaGlyLeuGluAsnProAsnGlu100ValThrValSerThrAlaSer120Gly105AlaLeu90ThrGin75TyrSer60PheTrp45Leu30lieGlyArgGinSerArgSerLeuLysLeu80AlaPheSerThrPheCysAlaAspProLysGly125Trp110ProArg95GlyGinSerValPheProLeuAlaProSerSerLysSerThrSerGlyGlyThrAlaAla[4005]130135140[4006]LeuGlyCysLeu[4007]145[4008]SequenceID295[4009]ctcgagcagtctggggcggaggtgaagaagccgggggagtctctgaggatctcctgtaag60[4010]ggttctggatacagcttttccacctactggatcgcctgggtgcgccagatgcccgggaaa120[4011]ggcctggagtggatgggcatcatctatcctggtgactctgatgtcaagtacagcccgtct180[4012]ttccaaggccaggtcaccatctcagccgacaggtccatcggcgccgcctacctgcagtgg240[4013]agcagactgaaggcctcggacaccgccatgtatttctgtgcgagacaagatgataggggc300[4014]tattacttctatgactattggggccagggaaccctggtcaccgtctcctcagcttccacc360[4015]aagggcccatcggtcttccccctggcgccctgctccaggagcacctctgggggcacagcg420[4016]gccctgggctgcctggtcaaggact445SequenceIDLeuGluGin1lieTrpTyrSerCys296SerLys20GinGlyAla5GlySerValArg35GlyAspSerAspGluValLysGlyTyrMetProGlyPro50ValThr65SerArgLeuLysLys40LysSer25GlyProGlyGluSerSerThrTyrLeuGluTrpLys10PhelieSerAlaAsp70AlaSer85Val55ArgSerTyrSerProlieGlyAspThrAlaMet90Ser60AlaAla75TyrPheMet45PheTrp30GlyLeu15lieTyrCysAlalieGinGlyLeuGinArg95ArgAlalieGinTrp80Gin[4030]AspAspArgGlyTyrTyrPheTyrAspTyrTrpGlyGinGlyThrLeu[4031]100105110[4032]ValThrValSerSerAlaSerThrLysGlyProSerValPheProLeu[4033]115120125[4034]AlaProCysSerArgSerThrSerGlyGlyThrAlaAlaLeuGlyCys[4035]130135140[4036]LeuValLysAsp[4037]145[4038]SequenceID297[4039]tctccatctt(ocgtgtctgcatctgtagga.gacagagtcactatcacttgtcgggcgact60[4040]cagggtattaj？tagttggttagcctggtatcaacagaaaccagggaaaccacctaaactc120[4041]ctgatttttgj？tgcatctagtttgcaaagtggggtcccatcaaggttcagcggcagtgga180[4042]tctgggacagatttcactctcaccatcagcagtctacagcctgaagattttgcaacttac240[4043]ttttgtcaacaggctcacagtttcccgctcactttcggcggcgggaccaaggtggagatc300[4044]aaacgaactgtggctgcaccatct324[4045]SequenceID298[4046]SerProSerSerValSerAlaSerValGlyAspArgValThrlieThr[4047]151015[4048]CysArgAlaThrGinGlylieSerSerTrpLeuAlaTrpTyrGinGin[4049]202530[4050]LysProGlyLysProProLysLeuLeuliePheGlyAlaSerSerLeu[4051]354045[4052]GinSerGlyValProSerArgPheSerGlySerGlySerGlyThrAsp[4053]505560[4054]PheThrLeuThrlieSerSerLeuGinProGluAspPheAlaThrTyr[4055]65707580[4056]PheCysGinGinAlaHisSerPheProLeuThrPheGlyGlyGlyThr[4057]859095[4058]LysValGlulieLysArgThrValAlaAlaProSer[4059]100105[4060]SequenceID299[4061]tctccatcct(occtgtctgcatctgtaagagacagagtcaccatcacttgccaggcgagt60[4062]caggacattaj？caccaatttaaattggtatcagaagaaatcaggcaaacctcctaagctc120[4063]ttgatctacgatgcatccaatttggaaacaggggtcccatcaaggtttggtggaagtgga180[4064]tctgggacagattttactttcaccatcagcaacctgcagcctgaagattttgcaacatat240[4065]tactgtcaacattatgataatgtcccattcactttcggccctgggaccaaagtggatatc300[4066]agacgaactgtggctgcaccatct324[4067]SequenceID300[4068]SerProSerSerLeuSerAlaSerValArgAspArgValThrlieThr1CysGinAla5GinAsplieSerLysGluPhe65TyrSerGly35GlySer20LysProProLysThr50ThrCysLysValPheGinHisAspValProSerThrlieLeu40PheThr25Leu10AsnLeuTyr85ArgSer70AspArg55AsnLeuGlyGinProlieGlySerAsnTrpTyrAspGly60AspAla45SerAsnArgThrValProValGlu75ThrPheTyr30SerGlyAlaPhe90AlaProSerPheGlyPro15GinLysAsnLeuThrAspThrGly95Tyr80ThrlieArgArgThrValAla100105SequenceID301tctccatcctccctgtctgcatctgtaggagacagagtcacaggacataagcagaaatttaaattggtatcagcaaaagcctgatctacggtgcatccactttggaaacaggggtcccattctgggacagattttactttcaccatcagcagcctgcagctactgtcaacagtatgatgctctcccgtacacttttggccttacgaactgtggctgcaccatctSequenceID302SerAlaSerValccatcacttgccaggcgagt60cagggaaagcccctgtgctc120caaggttcagtggaggtgga180ctgaagatgttgccacattc240cggggaccaggctggagttc300324SerProSerSer1CysGinAlaLysProGluPhe65TyrThr50ThrGly35GlySer20LysLeu5GinAsplieSerAlaProValCysArgLeuSequenceIDPheGinGluValProSerThrlieGinLeu40PheArg25LeuGlyAsp10AsnLeulieSerGlyPhe100303Tyr85LeuSer70AspArg55SerLeuGinProTyrGlyArgValThrAsnTrpGlyGly60AspAla45SerTyr30Serlie15GinThrGinAlaLeuProArgThrValAla105Glu75ThrPheGlyAlaTyr90AlaProSerValGlyProThrLeuThrAspThrGly95Phe80Thrtctccatcctccctgtctgcatctgtaggagacagagtcacaggacattagcacctatttaaattggtatcagcagaaacctgatctacgatgcatccaatttggaaacacgggtcccatccatcacttgccaggcgagtcagggaaagcccctaaactccaaggttcggtggaagtgga601201801324108]tctggaaaagactttactctcaccatcaacagcctgcagcctgaagattttgcaacatat2404109]tactgtcaacagtatgatcattacccgatcaccttcggccaagggacacgactggagatt3004110]aaacgaactgtggctgcaccatct3244111]SequenceID3044112]SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr4113]1510154114]CysGinAlaSerGinAsplieSerThrTyrLeuAsnTrpTyrGinGin4115]2025304116]LysProGlyLysAlaProLysLeuLeulieTyrAspAlaSerAsnLeu4117]3540454118]GluThrArgValProSerArgPheGlyGlySerGlySerGlyLysAsp4119]5055604120]PheThrLeuThrlieAsnSerLeuGinProGluAspPheAlaThrTyr4121]657075804122]TyrCysGinGinTyrAspHisTyrProlieThrPheGlyGinGlyThr4123]8590954124]ArgLeuGlulieLysArgThrValAlaAlaProSer4125]1001054126]SequenceID3054127]tctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccaggcgagt604128]caggacattaacaacgacttaaattggtatcagcagaaaccagggaaagcccctaagctc1204129]ctgatgtacgatgcatccaatttggaagtgggggtcccatttaggtacagtggaagtgga1804130]tctgggacagattttactttcaccgtcggcagcctgcagcctgaagatgttgcaacatat2404131]tactgtcaacagtatcatgatctccctcacacttttggccaggggaccaagctggagttc3004132]taacgaactgtggctgcaccatct3244133]SequenceID3064134]SerProSerSerLeuSerAlaSerValGlyAspArgValThrlieThr4135]1510154136]CysGinAlaSerGinAsplieAsnAsnAspLeuAsnTrpTyrGinGin4137]2025304138]LysProGlyLysAlaProLysLeuLeuMetTyrAspAlaSerAsnLeu4139]3540454140]GluValGlyValProPheArgTyrSerGlySerGlySerGlyThrAsp4141]5055604142]PheThrPheThrValGlySerLeuGinProGluAspValAlaThrTyr4143]657075804144]TyrCysGinGinTyrHisAspLeuProHisThrPheGlyGinGlyThr4145]8590954146]LysLeuGluPheLeuArgThrValAlaAlaProSer4147]4148]4149]4150]4151]4152]4153]4154]4155]4156]4157]4158]4159]4160]4161]4162]4163]4164]4165]4166]4167]4168]4169]4170]4171]4172]4173]4174]4175]4176]4177]4178]4179]4180]4181]4182]4183]4184]4185]100105SequenceID307tctccactctccctgtctgcatctgtgggagacagaatcactgaccattggtagatatgtaaattggtatcagcagaggcctgatctatgctgcatctaccttgcatattgtggtcccattctggcacagatttcactctcaccatcaacagtctgcaacttctgtcaagagaattacagtgccacgcgcacttttggccaagcgaactgtggctgcaccatctSequenceID308SerProLeuSerccatctcttgccgggcaagtcaggggaagcccccaaactccaaggttcagtggcagtggcgtgaagactttgcaatttacaggggaccaaggtggagatc1CysArgAlaLeu5LeuArgProGly35ValSer20GluAlaProLysSerAlaSerValThrlieGlyHislie50ThrLeuPhe65PheCysLysValGinGluValProSerThrlieGluLeu40PheArg25LeuGly10TyrAspValTyrAsn70TyrSerArg55SerLeulieSerGlySerArgArglieThrAsnTrpAlaAsn85LysArgThrAlaValGinThrGly60AspGlu75ArgThrPhe90AlaProSerAla45SerPheGlyTyr30SerGlyAlaGinlieSer15GinGinThrLeuThrAsplieGly95Tyr80ThrlieLysArgThrValAla100105SequenceID309tctccatcctccctgtctgcatctgtaggagacagagtcacagaacattggcatctatttaaattggtatCclCCclCclclclCctgatctttggtgcatccactttgcaaagtggggtcccattctgggacagatttcactctcaccatcagcagtstgcaactactgtcaacagagttacagtacccctctcaccttcggcgSequenceID310SerSer1CysLysGinPheProSerSerArgAlaProGly35SerGly50ThrLeuSer20GinValThrLeu5GinAlaProlieAsnProSerSerAlalieGluSerValGlyLeu40PheArg55SerLeulie25LeuSerGinGly10TyrlieGlyProAspLeuPheSerAspArgAsnGlyValThrTrpAla45SerGly60AspLeuTyr30SerGlyAlalie15HisThrThrThrThrHisLeuAspTyr60120180240300324ccatcacttgccgggcaagt60cagggcaagcccctgagctc120caaggttcagtggcagtgga180ctgacgatttggcaacttac240gggggaccaaggtgg29565707580TyrCysGinGinSerTyrSerThrProLeuThrPheGlyGlyGlyThr859095LysValSequenceID311tctccatcctccctgtctgcttctgtaggagacagagtctccatcacttgccgggcaagtcagagcattagcaactatttaaattggtatcagcagacaccagggaaagcccctaaactcctgatctatgctgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtggatctgggacagatttcactctcaccatcagcagtctacaacctgaagattttgcaacttacttctgtcaacagagttacagtaccccgtggacgttcggccaagggaccaaggtggSequenceID312SerAlaSerValGlyAspArgValSerlieSerProSerSerLeu15CysArgAlaSerGinThrProGinPhe65PheSer50ThrGly35GlySer20LysAlaProLysSerlieSerAsn25Leu10TyrLeuValProSerLeuThrlieCysGinGinSer85Leu40PhelieSerGlySerAsnTrpTyrAlaArg55SerLeuGinProSer70TyrSerThrProGly60AspTrp90Glu75ThrPheAla45SerPheGlyTyr30SerGlyAlaGin15GinThrGinSerLeuThrAspThrGly95Tyr80ThrLysValSequenceID313tctccatcgtccctgtctgcatctataggagacatagtcacagggcacttccaattttgtaaattggtatcagcagaaacctgatctatactgcatccactttgcaaagtggggtcccattctgggacagatttcactctcaccatcagcagtctacaacttctgtcaacagagttacagtaccccgtggacgttcggccSequenceID314SerProSerSerLeuSerAlaSerlieGlyAsp1510CysArgAlaSerGinGlyThrSerAsnPheVal2025LysProGlyLysAlaProLysLeuLeulieTyr3540GinSerGlyValProSerArgPheSerGlySer5055ccatcacttgccgggcaagtcagggaaagcccctaaactccaaggttcagtggcagtggactgaagattttgcaacttacaagggaccaaggtggalieValThrlieThr15AsnTrpTyrGinGin30ThrAlaSerThrLeu45GlySerGlyThrAsp606012018024029560120180240296[4225]PheThrLeuThrlieSerSerLeuGinProGluAspPheAlaThrTyr65707580PheCysGinGinSerTyrSerThrProTrpThrPheGlyGinGlyThr859095LysValSequenceID315SequenceID316SerProSerSerLeuSerAlaSerValGlyAspArgValThrLeuThr151015CysArgAlaSerGinThrValAsnAsnTyrLeuHisTrpTyrGinGin202530LysProGlyLysAlaProLysLeuLeulieTyrAlaSerSerThrLeu354045GinSerGlyValThrSerArgPheSerGlySerGlySerGlyThrAsp505560PheThrLeuThrlieThrSerLeuGluValAspAspPheAlalieTyr65707580TyrCysGinGinSerTyrSerThrProTrpThrPheGlyGinGlyThr859095LysValGlulieLysArgThrValAlaAlaProSer100105SequenceID317tctccatccttcctgtctgcatctgtcggagacagagtcaccatcacttgccgggccagt60cagggcattaccacttatttagcctggtatcagcaaaaaccagggagagcccctaagctc120ctgatctattctgcatccactttgcaaagaggggtcccatcaagattcagcggcagtgga180tctgggacagagttcgctctcacaatcagcagcctgcagcctgaagattctgcaacttat240tactgtcaagaacttgatagttacccctacacttttggccaggggaccaagctggagttc300cactaactgtggctgcaccatct323SequenceID318SerProSerPheLeuSerAlaSerValGlyAspArgValThrlieThr151015CysArgAlaSerGinGlylieThrThrTyrLeuAlaTrpTyrGinGin202530tctccatcctcactgtctgcctctgtaggagacagagtcaccttgacttgccgggcaagtcagaccgttaacaactatttacattggtatcagcagaaaccagggaaagcccctaaactgctgatctacgcctcatccactttgcaaagtggggtcacgtcaaggttcagtggcagtggatctgggacagacttcactctcaccatcaccagtctcgaggttgacgattttgcaatttactactgtcaacagagttacagtaccccgtggacattcggccaagggaccaaagtggaaatcaaacgaactgtggctgcaccatct120180240300324136CN10855243A說(shuō)明書133/175頁(yè)[4264LysProGlyArgAlaProLysLeuLeulieTyrSerAlaSerThrLeu[4265354045[4266GinArgGlyValProSerArgPheSerGlySerGlySerGlyThrGlu[4267505560[4268PheAlaLeuThrlieSerSerLeuGinProGluAspSerAlaThrTyr[426965707580[4270TyrCysGinGluLeuAspSerTyrProTyrThrPheGlyGinGlyThr[4271859095[4272LysLeuGluPheHis[4273100[4274SequenceID319[4275tctccactcaocctgcccgtcacccctggagagtcggcctccatctcctgcaaatctagt60[4276cagagcctcc:gcagagtaatggatacaactatttggattggtacgtggtgaagccaggg120[4277cagtctccacaactcctgatctacttgggctctaatcgggcctccggggtccctgacagg180[4278ttcagtggcagtggatcaggcaccgattttacactggaaatcagtagagtggaggctgag240[4279gatgttggac:ttatttctgcatgcaagctctgcacactcctagcatgtacacttttggc300[4280caggggacca3ggtggagatcaaacgaactgtggctgcaccatct345[4281SequenceID320[4282SerProLeuThrLeuProValThrProGlyGluSerAlaSerlieSer[4283151015[4284CysLysSerSerGinSerLeuLeuGinSerAsnGlyTyrAsnTyrLeu[4285202530[4286AspTrpTyrValValLysProGlyGinSerProGinLeuLeulieTyr[4287354045[4288LeuGlySerAsnArgAlaSerGlyValProAspArgPheSerGlySer[4289505560[4290GlySerGlyThrAspPheThrLeuGlulieSerArgValGluAlaGlu[429165707580[4292AspValGlyLeuTyrPheCysMetGinAlaLeuHisThrProSerMet[4293859095[4294TyrThrPheGlyGinGlyThrThrValGlulieLysArgThrValAla[4295100105110[4296AlaProSer[4297115[4298SequenceID321[4299tctccactcaocctgcccgtcacccctggagagtcggcctccatctcctgcaaatctagt60[4300cagagcctcc:gcagagtaatggatacaactatttggattggtacgtggtgaagccaggg120[4301cagtctccacaactcctgatctacttgggctctaatcgggcctccggggtccctgacagg180[4302ttcagtggcagtggatcaggcaccgattttacactggaaatcagtagagtggaggctgag240137[4303gatgttggactttatttctgcatgcaacatgcaagctctcgtagcatgtacacttttggc300[4304caggggaccaegg313[4305SequenceID322[4306SerProLeuThrLeuProValThrProGlyGluSerAlaSerlieSer[4307151015[4308CysLysSerSerGinSerLeuLeuGinSerAsnGlyTyrAsnTyrLeu[4309202530[4310AspTrpTyrValValLysProGlyGinSerProGinLeuLeulieTyr[4311354045[4312LeuGlySerAsnArgAlaSerGlyValProAspArgPheSerGlySer[4313505560[4314GlySerGlyThrAspPheThrLeuGlulieSerArgValGluAlaGlu[431565707580[4316AspValGlyLeuTyrPheCysMetGinHisAlaSerSerArgSerMet[4317859095[4318TyrThrPheGlyGinGlyThrThr[4319100[4320SequenceID323[4321tctccaggcaccctgtctttgtctccaggggaaagagccaccctctcctgcagggccagt60[4322cagagtgttagcagttcctctttggcctggtaccaacagaaacctggccaggctcccagg120[4323gtcctcatctttgetgeagecagcagggccactggcatcccagacaggttcagtggcagt180[4324gggtctgggacagagttcactctcaccatcagcagggtggagcctgaagattttgcagtg240[4325tatttctgtcagcactatgataactcaccgaggttcacttttggccaggggaccaagctg300[4326gagaactaacgaactgtggctgcaccatct330[4327SequenceID324[4328SerProGlyThrLeuSerLeuSerProGlyGluArgAlaThrLeuSer[4329151015[4330CysArgAlaSerGinSerValSerSerSerSerLeuAlaTrpTyrGin[4331202530[4332GinLysProGlyGinAlaProArgValLeuliePheAlaAlaAlaSer[4333354045[4334ArgAlaThrGlylieProAspArgPheSerGlySerGlySerGlyThr[4335505560[4336GluPheThrLeuThrlieSerArgValGluProGluAspPheAlaVal[433765707580[4338TyrPheCysGinHisTyrAspAsnSerProArgPheThrPheGlyGin[4339859095[4340GlyThrLysLeuGluAsn[4341100[4342SequenceID325[4343tctccaggcaccctgtctttgtctccaggagaaagagccaccctctcctgcagggccagt60[4344cagaatgttggcggcagctacttagcctggtaccagcagaaacctggccaggctcccagg120[4345ctcctcatctatggtgcatccagcagggccactggcgtcccagacaggttcagtggcagt180[4346gggtctgggacagacttcattctcaccatcagcagactggagcctgaagattttgcagtg240[4347tattactgtcagcagtatggtagctcaccgggattcactttcggccctgggaccaaagtg300[4348gatatcaaacgaactgtggctgcaccatct330[4349SequenceID326[4350SerProGlyThrLeuSerLeuSerProGlyGluArgAlaThrLeuSer[4351151015[4352CysArgAlaSerGinAsnValGlyGlySerTyrLeuAlaTrpTyrGin[4353202530[4354GinLysProGlyGinAlaProArgLeuLeulieTyrGlyAlaSerSer[4355354045[4356ArgAlaThrGlyValProAspArgPheSerGlySerGlySerGlyThr[4357505560[4358AspPhelieLeuThrlieSerArgLeuGluProGluAspPheAlaVal[435965707580[4360TyrTyrCysGinGinTyrGlySerSerProGlyPheThrPheGlyPro[4361859095[4362GlyThrLysValAsplieLysArgThrValAlaAlaProSer[4363100105110[4364SequenceID327[4365tctccaggcaccctgtctttgtctccaggggaaagagccaccctctcgtgcagggccagt60[4366cagagtgttagcaacaacttcttagcctggtaccagcagaaacctggccaggctcccagg120[4367ctcctcatctatggtgcatccagcagggccactggcgtcccagacaggttcagtggcagt180[4368gggtctgggacagacttcattctcaccatcagcagactggagcctgaagattttgcagtg240[4369tattactgtcagcagtatggtagctcaccgggattcactttcggccctgggaccaaagtg300[4370gatatcaaacgaactgtggctgcaccatct330[4371SequenceID328[4372SerProGlyThrLeuSerLeuSerProGlyGluArgAlaThrLeuSer[4373151015[4374CysArgAlaSerGinSerValSerAsnAsnPheLeuAlaTrpTyrGin[4375202530[4376GinLysProGlyGinAlaProArgLeuLeulieTyrGlyAlaSerSer[4377354045[4378ArgAlaThrGlyValProAspArgPheSerGlySerGlySerGlyThr[4379505560[4380AspPhelieLeuThrlieSerArgLeuGluProGluAspPheAlaVal139657075TyrTyrCysGinGinTyrGlySerSerProGly8590GlyThrLysValAsplieLysArgThrValAla100105SequenceID329tctccaggcaccctgtctttgtctccaggggaaagagccacagagtgttagcaacaacttcttagcctggtaccagcagactcctcatctatggtgcatccagcagggccactgacatccgggtctgggacagacttcactctcaccatcagcagactggtattactgtcaacagtatgatacctcagttccggtcacttgaggtcttacgaactgtggctgcaccatctSequenceID330SerLeuSerPro80PheThrPheGlyPro95AlaProSer110ccctctcgtgcagggccagtaacctggccaggctcccaggcagacaggttcagtggcagtaggctgacgattttgctgtttcggcggagggaccaaggtgSerProGlyThrLeu15CysArgAlaSerGinArgAlaGinLysSer20GlyGinAlaProPro35ThrAsplieProGlyGluArg10SerValSerAsnAsnPheLeu25LeuLeulieTyrAlaThrAlaArgAla50PheThrLeuThrArg40ArgPheSerGlyAsp65TyrTyrCysGlyThrLysAsp55SerArgLeuGlulie70TyrAspThrSerGinGin85GluValLeuArgVal90ValAla75ProSer60AspGly45GlyAspThrTrp30AlaLeuSer15TyrGinSerSerSerGlyThrAlaValGluValLeuArgThr100105SequenceID331tctccaggcaccctgtctttgtctccaggggaaagagccacagagtgtcagcaacaacttcctagcctggtaccagcagactcctcatctatggtgcatccagcagggccactgacatccgggtctgggacagacttcactctcaccatcagcagactggtatcactgtcaacagtatggtacctcagttccggtcacttgagatcaaacgaactgtggctgcaccatctSequenceID332SerProGlyThrLeuSerLeuSerProGlyGlu1510CysArgAlaSerGinSerValSerAsnAsnPhe2025ValAlaAlaProPhePheSer110Gly95Val80GlyccctctcgtgcagggccagtaacctggccaggctcccaggcagacaggttcagtggcagtaggctgaggattttgctgtttcggcggagggaccaaggtgArgAlaThrLeuSer15LeuAlaTrpTyrGin306012018024030033060120180240300330140[4420]GinLysProGlyGinAlaProArgLeuLeulieTyrGlyAlaSerSer[4421]354045[4422]ArgAlaThrAsplieProAspArgPheSerGlySerGlySerGlyThr[4423]505560[4424]AspPheThrLeuThrlieSerArgLeuGluAlaGluAspPheAlaVal[4425]65707580[4426]TyrHisCysGinGinTyrGlyThrSerValProValThrPheGlyGly[4427]859095[4428]GlyThrLysValGlulieLysArgThrValAlaAlaProSer[4429]100105110[4430]SequenceID333[4431]tctccaggcaccctgtctttgtctccaggggaaagagccaccctctcgtgcagggccagt60[4432]cagagtgttagcaacaacttcttagcctggtaccagcagaaacctggccaggctcccagg120[4433]ctcctcatctatggtgcatccagcagggccactgacatcccagacaggttcagtggcagt180[4434]gggtctgggacagacttcactctcaccatcagcagactggaggctgaggattttgctgtt240[4435]tatcactgtcaacagtatggtacctcagttccggtcactttcggcggagggaccaaggtg300[4436]gagatcaaacgaactgtggctgcaccatct330[4437]SequenceID334[4438]SerProGlyThrLeuSerLeuSerProGlyGluArgAlaThrLeuSer[4439]151015[4440]CysArgAlaSerGinSerValSerAsnAsnPheLeuAlaTrpTyrGin[4441]202530[4442]GinLysProGlyGinAlaProArgLeuLeulieTyrGlyAlaSerSer[4443]354045[4444]ArgAlaThrAsplieProAspArgPheSerGlySerGlySerGlyThr[4445]505560[4446]AspPheThrLeuThrlieSerArgLeuGluAlaGluAspPheAlaVal[4447]65707580[4448]TyrHisCysGinGinTyrGlyThrSerValProValThrPheGlyGly[4449]859095[4450]GlyThrLysValGlulieLysArgThrValAlaAlaProSer[4451]100105110[4452]SequenceID335[4453]tctccaggcaccctgtctttgtctccaggggaaagagccaccctctcctgcagggccagt60[4454]cagagtgttagtaggagctacttagcctggtaccaacagaaacctggccaggctcccagg120[4455]ctcctcatctatggtgcatccagcagggccactggcatcccagacaggttcagtggcagt180[4456]gggtctgggacagacttcactctcagcatcagcggactggagcctgaagattttgcagtg240[4457]tatttctgtcagcagtttggtggctcacagtacacttttggccaggggaccaagctggag300[4458]atcaaacgaactgtggctgcaccatct327SequenceIDSerProGly1CysGinArgAsp65ArgLysAla50PheAlaPro35Thr336ThrSer20GlyLeu5GinSerLeuSerProGinGlylieProThrLeuSerlie70SerValSerAlaProAsp55SerArg40ArgArg25LeuGly10SerGluArgAlaThrTyrLeuAlaLeulieTyrPheSerGlyLeuGluGlySer60ProGlu75Gly45GlyTrp30AlaSerLeu15TyrSerGinSerSerAspPheGlyAlaThrVal80TyrPheCysGinGinPheGlyGlySerGinTyrThrPheGlyGinGly[4471]859095[4472]ThrLysLeuGlulieLysArgThrValAlaAlaProSer[4473]100105[4474]SequenceID337[4475]tctccagactccctggctgtgtctccgggcgggagggccaccatcaagtgcgcgtccagc60[4476]cagagtgttttggacaactccaaccataagaactccttggcgtggtaccagcagaaacca120[4477]ggactgcctcctaaactgctcatttactgggcatctacccggtattccggggtccctgac180[4478]cgattcagtggcagtgggtctgggacagatttcactctcaCC3.tC3-3.C3.3.cctgcaggct240[4479]gccgatgtggcagtttatttctgtcagcaatattatagtactccgtggaccttcggccag300[4480]gggaccaaggtggagc316SequenceIDSerProAsp1CysLeuTyrSer65AlaThrAlaAlaTrp50GlyAspPheSerTrp35AlaSerValGly338SerSer20TyrSerGlyAlaLeu5GinGinThrThrVal85GlyAlaSerGinArgAsp70TyrValValLysTyr55PheSerProPheThrLysLeuPro40SerThrCysValAsp25GlyGly10AsnGlyArgAlaThrSerAsnHisLeuProProGlyValProAsp60Lys45ArgLys30Leulie15AsnLeuLeuGinThrGin90PheSerAsnLeuGinlieAsn75TyrTyrSerThrPro95LysSerlieGlyAla80TrpGlu105Gin100SequenceID339tctccagactccctggctgtgtctccgggcgggagggccaccatcaagtgcgcgtccagc60cagagtgttttggacaactccaaccataagaactccttggggactgcctcctaaactgctcatttactgggcatctaccccgattcagtggcagtgggtctgggacagatttcactctcagaggatgtggctttttattactgtcagcaatattatagtagggaccaaggtggagatcaaacgaactgtggctgcaccatSequenceID340AlaValSerProGlyGlySer1CysLeuTyrSer65GluProAlaAlaTrp50GlyAspSerSerAspThrPheTrp35AlaSerValGlySer20TyrSerGlyAlaGin100Leu5GinGinThrThrSerGinArgAsp70TyrValLeuLysPhe85GlyThrTyr55PheTyrLysPro40SerThrCysValAsp25GlyGlyLeuGinGlu10510AsnLeuValThrcgtggtaccagcagaaaccaggtattccggggtccctgacccatcagcagcctgcaggctctccgtggaccttcggccagctSerProProlie75TyrGin90lieLysArgAsnProAsp60SerTyrArgAlaThrHisLys45ArgSerSerThrLys30LeuPheLeuThrVal110lie15AsnLeuSerGinLysSerlieGlyAla80TrpPro95AlaAlaProSerSequenceID341tctccagactccctggctgtgtctctgggcgagagggccacagagtcttttgtacagctccagcaataagaactacttagggacagtctcctaagttgctcatttactgggcttcttccccgattcagtggcagcgggtctgggacagatttcactctcagaggatgtggctttttattactgtcagcaatattataatagggaccaaggtggaagtcaaacgaactgtggctgcaccatSequenceID342AlaValSerLeuGlyGluccatcaactgcaagtccagccttggtaccagcagaaaccagggaatccggggtccctgccccatcagcagcctgcaggctctcctcgaacgttcggccagctSerProAspSerLeu15CysLysSerSerGinLysSerLeuAlaTyrTrp50SerGly65Trp35AlaSerGinSerLeuLeuTyr2025TyrGinGinLysProGly10SerArgAlaThrSerSerAsnGinLysSerSerArgSerGlyThrAsp70Glu55PhePro40SerGinSerProGlyValProThrLeuThrlie75Ala60SerLys45ArgLys30Leulie15AsnAsnTyrLeuliePheSerGly12018024030034260120180240300342SerLeuGinAla80GluAspValAlaPheTyrTyrCysGinGinTyr8590ThrPheGlyGinGlyThrLysValGluValLys100ProSerSequenceID343tctccagaatacttggctgtcggagtgttttagacagctcgggcagcctcctaaactactcgattcagtggcagcgggtcgttgatgtggcagtttattagggaccaaggSequenceID344SerProGluTyr105gtctctgggcgagagggccacaacaataagaacttcttggcatttattgggcatctaccctgggacagatttcactctcactgtcaggagtatttttgtaTyrAsnThrProArg95ArgThrValAlaAla110ccatcaactgcaagtccagccctggtaccaacaaaaaccagggaatccggggtccctgacccattagcagcctgcaggctctccgtggacgttcggccaa1CysLysSerLeuAlaTrp35TyrTrpAla50GlySer20TyrGinGinLysAlaValSerLeuGlyGlu10SerSerLeu5ArgSerValLeuArgAsnAsp25GlyGinProProAlaThrAsnPro40SerGlyValProSer65ValAspValAlaSerThrArgGlu55PheThrLeuThrSerGlyThrAsp70ValTyrTyrCysGin85GlyThrLysAsp60SerLys45ArgLys30Leulie15AsnAsnPheLeuliePheSerGlyGlu90lie75TyrPheCysThrSerLeuGinAla80ProTrp95ThrPheGlyGin100SequenceID345caggtgaaactgctcgagtcgggggctgaggtgaagaagctcctgcgagacttctggttacgattttaccagctacagtgcctggacaaggacttgagtggatgggatggatcagcccttgcacagactctccaggacagagtcaccttgaccaccgacaatggaactgcggagcctgagatccgacgacacggccatttagcagctggtacgagttggaccactggggccagggaatccSequenceID346GinValLysLeuLeuGluSerGlyAlaGluVal1510SerValLysValSerCysGluThrSerGlyTyr2025ctggggcctcagtgaaggtctcaactgggtgcgacaggccacaatggtaagagaaactatcatccacgaacacagcctacatttctgcgcgcgggaaggctggtcaccgtLysLysProGlyAla15AspPheThrSerTyr306012018024030031060120180240300350144[4576]SerValAsnTrpValArgGinAlaProGlyGinGlyLeuGluTrpMet[4577]354045[4578]GlyTrplieSerProTyrAsnGlyLysArgAsnTyrAlaGinThrLeu[4579]505560[4580]GinAspArgValThrLeuThrThrAspThrSerThrAsnThrAlaTyr[4581]65707580[4582]MetGluLeuArgSerLeuArgSerAspAspThrAlalieTyrPheCys[4583]859095[4584]AlaArgGluGlySerSerTrpTyrGluLeuAspHisTrpGlyGinGly[4585]100105110[4586]lieLeuValThr[4587]115[4588]SequenceID347[4589]caggtgaaactgctcgagtcgggggctgaggtgaagaagcctggggcctcagtgaaggtc60[4590]tcctgcgagacttctggttacgattttaccagctacagtgtcaactgggtgcgacaggcc120[4591]cctggacaagggcttgagtggatgggatggatcagcccttacaatggtaagagaaactat180[4592]gcacagactctccaggacagagtcaccttgaccaccgacacatccacgaacacagcctac240[4593]atggaactgcggagcctgagatccgacgacacggccatttatttctgcgcgcgggaaggc300[4594]agcagctggtacgagttggaccactggggccagggaatcctggtcaccgt350[4595]SequenceID348[4596]GinValLysLeuLeuGluSerGlyAlaGluValLysLysProGlyAla[4597]151015[4598]SerValLysValSerCysGluThrSerGlyTyrAspPheThrSerTyr[4599]202530[4600]SerValAsnTrpValArgGinAlaProGlyGinGlyLeuGluTrpMet[4601]354045[4602]GlyTrplieSerProTyrAsnGlyLysArgAsnTyrAlaGinThrLeu[4603]505560[4604]GinAspArgValThrLeuThrThrAspThrSerThrAsnThrAlaTyr[4605]65707580[4606]MetGluLeuArgSerLeuArgSerAspAspThrAlalieTyrPheCys[4607]859095[4608]AlaArgGluGlySerSerTrpTyrGluLeuAspHisTrpGlyGinGly[4609]100105110[4610]lieLeuValThr[4611]115[4612]SequenceID349[4613]caggtgaaactgctcgagtctgggggaggcttggtcaagcctggagggtccctgagactc60[4614]tcctgtgcaggctccggattcaccttcagtgactattccatgagctgggtccgccacgct120ccagggaggggcctggagtggcttgcagacattactggtggcagactctgtgaggggccgattcaccctctcccgggacactgcaaatggacagcctgagagtcgacgacacgggcaaatggttcgcgaatgagcccctttgaccactggggccagggaaSequenceID350GluSerGlyGlyGlyLeuttggtccttccgtgtactacacgccaagaggtcactgtatattactgtgccttgctctatcagtggtcacGinVal1SerLeuSerMetLysLeuArgSer35lieLeu20TrpAlaAsp50ArgGlyArg65LeuThrPheGinMetAspAlaLeuLeuGlyThrTyr100ValLeu5SerValGlyThrSer85GlyCysAlaGlyArgHisValLeu70LeuGly55SerAla40ProSer25Pro10GlyArgValGlySerValAsnArgSerArgMetAspAspSer105Asp90ProPheArgTyrAla75ThrValThrGlyTyr60LysLysPheProGly15AspGlyTyrSer30GluTrpLeuLeu45AlaAspSerValGlyPheAspHisArgSerLeuLysTyrTyr80CysTrp110Tyr95GlyGinVal115SequenceID351ggggaaagagccaccctctctggtaccagctaaaacctgggccactggcatcccagacagatcagtagactggagcctgaccggggatcactttcggcggtctSequenceID352GlyGluArgAlactgcagggccagtcagactgccaggctcccaggctcctcagttcagtggcggtgggtctgagattttgcactgtattgctagggaccacggtggagatcattagtagcacctacttagcctccatggtgcatccagcaggggacagacttcactctcaccgtcaacactacggtagctcaaacgaactgtggctgcacca1ThrTyrLeulieThrLeuSerCysArg5TrpTyrGinLeuHis35SerGlyGly50GluProGlu65LeuAla20GlyAlaSerSerGlySerGlyAspPheAla70Lys25ArgAla40AspPheAla10ProThr55LeuTyrCysCysThrThrLeuSerGinGinlieGlyGlyThrValAlaPro45liePro30AspSerSer15ArgLeuArgPheSerArgLeuGin75Thr60HisTyrGlySerSer8018024030035060120180240300303146ProGlylieThrPheGlyGlyGlyThrThrVal85ValAlaAlaProSer100SequenceID35390GlulieLysArgThr95ggagacagagtcaccatcacttgccgggcgagtcaggacattagcaattatttagcctgg60[4660]tttcagcagagacccgggaaagttcctaatctcctcatctatgctgcatccactttgcaa120[4661]tcaggggtcccatctcgattcagtggcagtggatctggaacagaattcactctcaccatc180[4662]agtagtctgcagcctgaagatggtgcaagttattactgtcaaaagtatgacggtgcccct240[4663]tggacgttcggccaggggaccaaggtggaaatcaaacgaactgtggctgcaccatctgtc300[4664]ttc303SequenceIDGlyAspArg1TyrLeuAla354ValTrp20AlaThrlieThrCysArg5PheGinGinArglieTyrAla35GlySerGlyThrPro25SerAlaSer10GlyLysGinValGlyValProAsplieProGlySer50GluAspSerThrLeuGin40PheThrLeuThrPro65TrpGlyAlaThrPheGlyGlu55TyrTyrCysGinAlaProSerVal100SequenceID355Gin85PheSer70GlyThrLysValGlu90Lys75lielie60TyrSer45SerAspLysArgAsn30ArgSerGlyThrSer15LeuPheLeuAlaVal95AsnLeuSerGinPro80Alaggagacagagtcaccatcacttgccaggcgagtcaggacattatcacctatttaaattgg60[4682]tatcagcagaaaccagggaaagcccctaaactcctgatctacgaagcatccgatttggaa120[4683]acaggggtcccatcaaggttcagtggaagtggatctgggacatattttactttcaccatc180[4684]agtagcctgcagtctgaagatattgcaacatattactgtcaacaatttgatagtctcccc240[4685]ctcactttcggcggagggaccaaggtggagatcaaacgaactgtggctgcaccatctgtc300[4686]tcc303SequenceID356GlyAspArgValThrlieThrCysGinAlaSer1510TyrLeuAsnTrpTyrGinGinLysProGlyLys2025lieTyrGluAlaSerAspLeuGluThrGlyValGinAsplielieThr15AlaProLysLeuLeu30ProSerArgPheSer1474693]4694]4695]4696]4697]4698]4699]4700]4701]4702]4703]4704]4705]4706]4707]4708]4709]4710]4711]4712]4713]4714]4715]4716]4717]4718]4719]4720]4721]4722]4723]4724]4725]4726]4727]4728]4729]4730]4731]35GlySerGlySerGlyThr50SerGluAsplieAla65LeuThrPheGlyTyr55Tyr40PheThrPheThrAlaProSerVal100SequenceID357Gly85SerThr70GlyThrTyrCysLysVallie60Phe45SerSerLeuGinGinGin75GlulieLys90AspSerLeuArgThrVal95Pro80AlaateSequenceIDGlyGluArg1AsnLeuAlalieTyrGly35GlySerGly50Gluccaccctctcctgcagggccagtcagagtgttagcagcaacttagcctgg60aacctggccaggctcccaggctcgtcatctatggtgcatccaccagggcc120cagccaggttcagtggcagtgggtctgggacagacttcactctcaccatc180agcctgaagattttgcagtttattactgtcageagegtagcgacttgcgg240aggggaccaaggtggagatcaaacgaactgtggctgcaccatctgtcttc300303358AlaTrp20AlaThrLeuSer5TyrGinGinCysLysArgAlaSer10GlyGinPro25ThrGlylieProGinSerValAlaProSerSer15LeuValSerThrArgAla40PheThrLeuThrPro65SerAspPheAlaPheGlyGinSerGlyThrAsp55TyrTyrCysGinProSerValPhe100SequenceID359Gly85lieVal70ThrLysValGlulie60ArgSerArg30AlaArgPheSer45AspSerLeuGlulie90Gin75LysArgThrAspLeuValAla95Arg80AlagtcSequenceID360ccaccctctcctgcagggccagtcagagtgtcagcagtagttacttagcc60agagacctggccggtctcccaggctcctcatctatggtgcatccagcagg120tcccagacaggttcagtggcagtgggtctgggacagagttcactctcacc180tgcagtctgaagattttgeagtttattactgtcagcagtatggcagcaca240ttggccaggggaccaaggtggagatgaaacgaactgtggctgcaccatct3003031484732]GlyGluArgAlaThrLeuSerCysArgAlaSerGinSerValSerSer4733]1510154734]SerTyrLeuAlaTrpTyrGinGinArgProGlyArgSerProArgLeu4735]2025304736]LeulieTyrGlyAlaSerSerArgAlaThrGlylieProAspArgPhe4737]3540454738]SerGlySerGlySerGlyThrGluPheThrLeuThrlieSerSerLeu4739]5055604740]GinSerGluAspPheAlaValTyrTyrCysGinGinTyrGlySerThr4741]657075804742]ProTyrThrPheGlyGinGlyThrLysValGluMetLysArgThrVal4743]8590954744]AlaAlaProSerVal4745]1004746]SequenceID3614747]ggggaaagagccaccctctcctgcagggccagtcagagtattaccagcagctacttagcc604748]tggttccagcagaaacctggccaggctcccaggctcctcatctttggtgcttccaccagg1204749]gccacaggcatcccagacaggttcagtggcagtgggtctgggacagacttcactctctcc1804750]atcagcagactggagcctgaagattttgcagtgtatttttgtcagcagtatggcagcaca2404751]ccgtacacttttggccaggggaccaaggtggagatgaaacgaactgtggctgcaccatct3004752]gtc3034753]SequenceID3624754]GlyGluArgAlaThrLeuSerCysArgAlaSerGinSerlieThrSer4755]1510154756]SerTyrLeuAlaTrpPheGinGinLysProGlyGinAlaProArgLeu4757]2025304758]LeuliePheGlyAlaSerThrArgAlaThrGlylieProAspArgPhe4759]3540454760]SerGlySerGlySerGlyThrAspPheThrLeuSerlieSerArgLeu4761]5055604762]GluProGluAspPheAlaValTyrPheCysGinGinTyrGlySerThr4763]657075804764]ProTyrThrPheGlyGinGlyThrLysValGluMetLysArgThrVal4765]8590954766]AlaAlaProSerVal4767]1004768]SequenceID3634769]ggggaaagagccaccctctcctgcagggccagtcagagtgtcagcacctatttagcctgg604770]taccaacagaaagctggccagcctcccaggctcctcatccacgatgcttccaagagggcc120[4771]actggcatcccagccaggttcagtggcagtgggtctgggacagacttcactctcaccatc180[4772]agcagcctggagcctgaggattttgcagtgtattactgtcagcagtatggtacctcaccg240[4773]ctcactttcggcggagggaccaaggtggagatcaaacgaactgtggctgcaccatctgtc300[4774]ttc303[4775]SequenceID364[4776]GlyGluArgAlaThrLeuSerCysArgAlaSerGinSerValSerThr[4777]151015[4778]TyrLeuAlaTrpTyrGinGinLysAlaGlyGinProProArgLeuLeu[4779]202530[4780]lieHisAspAlaSerLysArgAlaThrGlylieProAlaArgPheSer[4781]354045[4782]GlySerGlySerGlyThrAspPheThrLeuThrlieSerSerLeuGlu[4783]505560[4784]ProGluAspPheAlaValTyrTyrCysGinGinTyrGlyThrSerPro[4785]65707580[4786]LeuThrPheGlyGlyGlyThrLysValGlulieLysArgThrValAla[4787]859095[4788]AlaProSerValPhe[4789]100[4790]SequenceID365[4791]ggggaaagagccaccctctcctgcagggccagtcagagtattagtttccacttagcctgg60[4792]taccagcagaaacctggccaggctcccagtctcctcatctacggaacatccaccagggcc120[4793]actggtatcccagccaggttcagtggcagtgggtctgggacagagttcactctcaccatc180[4794]agcagcctgcagtctgaagattctgcggtttattactgtcagcagtatcataactggcct240[4795]cccctcactttcggcggagggaccaaggtggacatcaaacgaactgtggctgcaccatct300[4796]gtc303[4797]SequenceID366[4798]GlyGluArgAlaThrLeuSerCysArgAlaSerGinSerlieSerPhe[4799]151015[4800]HisLeuAlaTrpTyrGinGinLysProGlyGinAlaProSerLeuLeu[4801]202530[4802]lieTyrGlyThrSerThrArgAlaThrGlylieProAlaArgPheSer[4803]354045[4804]GlySerGlySerGlyThrGluPheThrLeuThrlieSerSerLeuGin[4805]505560[4806]SerGluAspSerAlaValTyrTyrCysGinGinTyrHisAsnTrpPro[4807]65707580[4808]ProLeuThrPheGlyGlyGlyThrLysValAsplieLysArgThrVal[4809]859095[4810AlaAlaProSerVal[4811100[4812SequenceID367[4813ggggaaagagocaccctctcctgcagggccagtcagagtattagtttccacttagcctgg60[4814taccagcagaaacctggccaggctcccaggctcctcatctatggggcatccaccagggcc120[4815actggtatcc^agccaggttcagtggcagtgggtctgggacagagttcactctcaccatc180[4816agcagcctgcagtctgaagattctgcggtttattactgtcagcagtatcataactggcct240[4817cccctcactttcggcggagggaccaaggtggacatcaaacgaactgtgactgcaccatct300[4818gtc303[4819SequenceID368[4820GlyGluArgAlaThrLeuSerCysArgAlaSerGinSerlieSerPhe[4821151015[4822HisLeuAlaTrpTyrGinGinLysProGlyGinAlaProArgLeuLeu[4823202530[4824lieTyrGlyAlaSerThrArgAlaThrGlylieProAlaArgPheSer[4825354045[4826GlySerGlySerGlyThrGluPheThrLeuThrlieSerSerLeuGin[4827505560[4828SerGluAspSerAlaValTyrTyrCysGinGinTyrHisAsnTrpPro[482965707580[4830ProLeuThrPheGlyGlyGlyThrLysValAsplieLysArgThrVal[4831859095[4832ThrAlaProSerVal[4833100[4834SequenceID369[4835ggggaaagagocaccctctcctgcagggccagtcagagtgtcagcagtagttacttagcc60[4836tggtatcaacagagacctggccggtctcccaggctcctcatctatggtgcatccagcagg120[4837gccactggcaxccagacaggttcagtggcagtgggtctgggacagacttcactctctcc180[4838atcagcagactggagcctgaagattttgcagtgtatttttgtcagcagtatggcagcaca240[4839ccgtacacttttggccaggggaccaaggtggagatgaaacgaactgtggctgcaccatct300[4840gtc303[4841SequenceID370[4842GlyGluArgAlaThrLeuSerCysArgAlaSerGinSerValSerSer[4843151015[4844SerTyrLeuAlaTrpTyrGinGinArgProGlyArgSerProArgLeu[4845202530[4846LeulieTyrGlyAlaSerSerArgAlaThrGlylieProAspArgPhe[4847354045[4848SerGlySerGlySerGlyThrAspPheThrLeuSerlieSerArgLeu1515055GluProGluAspPheAlaValTyrPheCysGin657075ProTyrThrPheGlyGinGlyThrLysValGlu85AlaAlaProSerVal100SequenceID371ggcccaggactggtgaagcctccgtcagcagtagtcattagagtggattgggagtatcaacgcgtcaccatatccgtagaaccgccgcagacacggctgtggctgctactcttactactaaccgtctcctcagcctccaccaaSequenceID372GlyProGlyLeuValLysProTrpGlu15ValSerGlyGlySerValSerSerSer2025ArgGinProProGlyThrGlyLeuGlu9060GinTyrGlySerThr80MetLysArgThrVal95ttgggagaccctgtccctcactactggggctggatccgccttattatgggagcaccaactcacgtccaggaaccagttctatattactgtacgagacatgctacttctacatggacgtctcctgcactgtagcccccaggacaacccgtcccctgaagctttgaggattgggggcaaaggctctggtggcgacgggactgccttaagagtgaactctctgtcctagttccgaccacggtcTyrPro35SerThrAsnTyrGly50ValAspThrSerLeu40ProThrLeuSer10HisTyrTyrTrplieGlyLeuThrTrpSer65ThrAlaAlaAspAsn55AsnGinPheSerArg70AlaValTyrTyrSerLeuLysSer60LysThr85GlyCysTyrSerLeu75ThrCysProSerSer100LysGlyThrThrVal120Tyr105ThrCys90TyrTyrArgTyrValSerSerSer45ArgLeuHisPheAla125Gly30lieValAsnValCys15TrpAsnThrSerThrlieTyrlieLeu80AspTyr110SerThrGlu95MetAspValTrpGly115SequenceID373ggcccaggactggtgaagccttgggagaccctgtccctcacctgcactgtctctggtggctccgtcagcagtagtcattactactggggctggatccgccagcccccagggacgggactggagtggattgggagtatcaattattatgggagcaccaactacaacccgtcccttaagagtcgcgtcaccatatccgtagacacgtccaggaaccagttctccctgaagctgaactctctgaccgccacagacacggctgtatattactgtacgagacatgttgaggattgtcctagttccggctgctactcttactactactacttctacatggacgtctggggcaaagggaccacggtc6012018024030036038360120180240300360152accgtctcctcagcctccaccaaSequenceID374Leu383Gly1ValArgTyrSer65ThrCysValProSerGinGly50ValAlaProTrpGlyGlyPro35SerAspThrSerGly20ProThrThrAspVal5SerGlyAsnSerThr85GlySer100LysGlyGly115SequenceID375gggggaggcgtggtccaaccatcttcgatacctatggcatgtggcggttatctggtttgattcaccatctccagagacaagacgaggatacggctatttatatgcccaatactttcagcaElCCclclSequenceID376GlyGlyGlyValLysValThrTyrArg70AlaCysThrProSerGlyAsn55AsnValTyrThrTrpSerLeu40ProGinTyrSerVal120GluThr10HisSer25GluSerPheTyrTrpLeuSerCys90TyrTyr105ThrValLeuTyrlieLysLeu75ThrTyrSerSerTyrGlySer60LysArgTyrSerLeuThrTrpSer45ArgLeuHisPheAla125Gly30lieValAsnValCys15TrpAsnThrSerThrlieTyrlieLeu80AspTyr110SerThrGlu95MetAsptggggggtcccttagactctgcactgggtccgccaggctctggaagtaatcaatactatgttccaggaatacactgtatcttactgtgcgagaatgggatttggggccagggcaccctggcctgtgcagcgtctggattccaggcaagggactggagtggcagagtccgtggagggccgatgcaaatgaacagcctgaaatttgtagtggtcccagttgctcaccgtctcctcagcctcc1AlaAlaProSerGlyPhe20LysVal5lieGinProPheSerAsn50ArgAsp65AspGluGly35GinTyrAsnAspThrGlyTyrAlaSerArgAspLeuGluGlyGlyThrTrp40SerTyr25ValSerLeuArgLeuSerCys1015GlyMetHisTrpValArgGlu55ThrLeuAlaValGluAla85Asn70lieTyrTyrTyrCysVallieGlyArg60MetTrp45PheVal30PheAlaGinGlyAspThrlieSerLeuGin75AlaArgMet90AsnSerLeuGlyPheCys95Lys80Ser60120180240300360365[4927]GlyProSerCysTyrAlaGinTyrPheGinHis100105LeuValThrValSerSerAlaSerThr115120SequenceID377gggggaggcttggtccagcctggggggtccctgaaactctaccttcagtgggtctactatacactgggtccgccaggcttgttggccgtattagagtcaaagctgtcggctacgagacaaggcaggttcaccatttccagagatgactcacagaacacggctgaaaaccgaggacacggccgtgtatttttgtactggctaactactacggtatggacgtctggggccaagggaccacggElCCclclSequenceID378GinProGlyGlySerLeuTrpGlyGinGlyThr110cctgtgcagcctctgggttc60ccgggaaagggctggagtgg120catatgctgcgtcggtgaag180cgtttctggaaatgcacagc240atggttcggggactaccgac300tcaccgtctcctcagcctcc360365GlyGlyGlyLeuVal15AlaSerGlyPheThrPheSerGlyPhe20LysGlyLeuGlu10ThrAlaSerGly35TyrGluThrThrSer25ValGlyArglieLysLeuSerCys15ArglieHisTrpValGly50SerArgAspAspTrp40AlaAlaSerValVal30Vallie65LeuLysThrGluGlyThrThrAsp100ValTyr55GinAsnThrAlaSer70ThrAlaValTyrLys60LeuArg45GlyArgAsp85AsnTyrTyrGlySerSerAlaSer120Met105ThrPhe90AspPhe75CysThrGluMetHisGlyTyrValTrpGlyGin110AlaGinAlaThrSer80GlySer95GlyThrLysPheThrValThr115SequenceID379gggggaaggctggcacagcccggggggtcgctgaggctctaactccttcagcagttatagtatgcattgggttcgccaggtgggtctccttcatcactggtagcggtcgaaccgttaagtcgattcactatctccagagacaatgacaagaaatcactttagaggcgaggacacggctgtatattactgtgtgacagattcccacgtggggccagggaaccctggtcaccgtctcctcagSequenceID380GlyGlyArgLeuAlaGinProGlyGlySerLeu1510cgtgtgtggtatctggagtactccagggaagggccttgagacgcagccgctttggagggcatttgcaattgagcagcctgcgctgaagacattggtggggcttgcaccaaArgLeuSerCysVal1560120180240300350[4966]ValSerGlyValAsnSerPheSerSerTyrSerMetHisTrpValArg[4967]202530[4968]GinAlaProGlyLysGlyLeuGluTrpValSerPhelieThrGlySer[4969]354045[4970]GlyArgThrValLysTyrAlaAlaAlaLeuGluGlyArgPheThrlie[4971]505560[4972]SerArgAspAsnAspLysLysSerLeuTyrLeuGinLeuSerSerLeu[4973]65707580[4974]ArgGlyGluAspThrAlaValTyrTyrCysValThrAspSerLeuLys[4975]859095[4976]ThrLeuValGlyProThrTrpGlyGinGlyThrLeuValThrValSer[4977]100105110[4978]SerAlaCysThr[4979]115[4980]SequenceID381[4981]gggggaaggctggcacagcccggggggtcgctgaggctctcgtgtgtggtatctggagta60[4982]aactccttcagcagttatagtatgcattgggttcgccaggctccagggaagggccttgag120[4983]tgggtctccttcatcactggtagcggtcgaaccgttaagtacgcagccgctttggagggc180[4984]cgattcactatctccagagacaatgacaagaaatcactttatttgcaattgagcagcctg240[4985]agaggcgaggacacggctgtatattactgtgtgacagattcgctgaagacattggtgggg300[4986]cccacgtggggccagggaaccctggtcaccgtctcctcagcttccaccaa350[4987]SequenceID382[4988]GlyGlyArgLeuAlaGinProGlyGlySerLeuArgLeuSerCysVal[4989]151015[4990]ValSerGlyValAsnSerPheSerSerTyrSerMetHisTrpValArg[4991]202530[4992]GinAlaProGlyLysGlyLeuGluTrpValSerPhelieThrGlySer[4993]354045[4994]GlyArgThrValLysTyrAlaAlaAlaLeuGluGlyArgPheThrlie[4995]505560[4996]SerArgAspAsnAspLysLysSerLeuTyrLeuGinLeuSerSerLeu[4997]65707580[4998]ArgGlyGluAspThrAlaValTyrTyrCysValThrAspSerLeuLys[4999]859095[5000]ThrLeuValGlyProThrTrpGlyGinGlyThrLeuValThrValSer[5001]100105110[5002]SerAlaSerThr[5003]115[5004]SequenceID383155tgggggaggctggcacagcccggggggtcgctgaggctctaactccttcagcagttatagtatgcattgggttcgccaggtgggtctccttcatcactggtagcggtcgaaccgttaagtcgattcactatctccagagacaatgacaagaaatcactttagaggcgaggacacggctgtatattactgtgtgacagattcccacgtggggccagggaaccctggtcaccgtctcctcagSequenceID384GinProGlyGlySerLeucgtgtgtggtatctggagtactccagggaagggccttgagacgcagccgctttggtgggcatttgcaattgagcagcctgcgctgaagacattggtggggcttccaccaaTrp1ValGlyArgLeuSerGlyVal20GlyAla5Asn10TyrSerMetHisGinAlaPro35ThrValGlyArg50ArgLysLysAspAsnAspSerPheSerSer25TrpValSerPheArgLeuSerCysVal15ValArgGlyLeuGlu40TyrAlaAlaAlaLeuValTrp30ThrSer65ArgGlyGluAspLys70AlaValAla55LysSerLeuTyrlie45ArgPheGly60GinLeuSerSerGlySerThrlieThrLeuValGly100ThrThr85ProThrTrpTyrTyrGlyGin105Cys90GlyLeu75ValThrAspSerThrLeuValThr110Leu95ValLeu80LysSerSerAlaSer115SequenceID385gccatggccgagctcacccagtctccatcctccctgtctgaccatcacttgccgggcaagtcagaccattagcatatattccagggaaaccccctaaactcctgatctattctgcatccctcaaggttcactggcagtggatctgggacagatttcactccctgaagattttgcaacttactactgtcaacagagttacacaagggacacgactggacttttacgaactgtggSequenceID386ThrGinSerProSerSerLeuSerAlacatctatgggagacagagtctaaattggtatcagcagaaagtttgcaaagtggggtcccatcaccatcagcagtctgcatgtagcttcataaccttcggcAlaMetAlaGluLeu15GlyAspArgValThrlieThr20TyrLeuAsnTrpTyrGinGin35lieTyrSerAlaSerArgLeu505510CysArgAlaSerGinThr25LysProGlyLysPro40GinSerGlyValSerMet15Serlielie30LysLeuLeuPro60Pro45SerArgPheThr6012018024030035060120180240300333156GlySerGlySerGlyThrAspPheThrLeuThr657075ProGluAspPheAlaThrTyrTyrCysGinGin8590lieThrPheGlyGinGlyThrArgLeuAspPhe100105SequenceID387gccatggccgagctcactcagtctccactccccctgcccgtccatctcctgcaggtctagtcagagcctcctccatagtatggtacctgcagaagccagggcagtctccacacctcctgagcctccggggtccctgacaggttcagtggcagtggatcagatcagcagagtggaggctgaggatgttggggtttattactcctcgaagttttggccaggggaccaagctggagSequenceID388AlaMetAlaGlu1GlySerSerPro65lieGluProAsnPro50AspSerAlaLeuGly35HisArgArgGinAla20TyrLeuPheValLeu5SerAsnLeuSerThrlieTyrlieGly70AlaThr100SequenceID389Glu85ProArgGinSerLeuTyr55SerGluSerSerProCysAsp40LeuGlyAspPheArg25TrpGlySerValGly105Leu10SerTyrSerGlylieSerSerLeuHis80SerTyrSerSerPhe95TyrGluLeuTrp110tcacccctggagagccggccatggatataattatttggattctatttgggttctaatcgggcacagattttacactgaaagcatgcaagctctacaaactProSerLeuAsnThr75ValGly90GinGlyLeuGinGinArg60AspTyrThrProValSerLys45AlaPheTyrLysLeu30ProSerThrCysLeu110Thr15LeuGlyGlyLeuMet95GluProHisGinValLys80GingccatggccgagctcacacagtctccaggcaccctgtcttaccctctcctgcagggccagccagactattagcaacaactaaagttggccaggctcccaggctcctcatctatggtgcatccagacaggttcagtggcagtgggtctgggtcggacttcagagcctgaagattttgcagtgtattactgtcagcagtatgttcggcccagggaccaaggtggaaatcaaacgatSequenceID390AlaMetAlaGluLeuThrGinSerProGlyThr1510GlyGluArgAlaThrLeuSerCysArgAlaSertgtctccaggggaaagagccacttagcctggtaccagcagccagcagggccactggcatcctctcaccatcagcagactggtacctcaccttcaaggacgLeuSerLeuSerPro15GinThrlieSerAsn6012018024030033360120180240300334[5083]202530[5084]AsnTyrLeuAlaTrpTyrGinGinLysValGlyGinAlaProArgLeu[5085]354045[5086]LeulieTyrGlyAlaSerSerArgAlaThrGlylieProAspArgPhe[5087]505560[5088]SerGlySerGlySerGlySerAspPheThrLeuThrlieSerArgLeu[5089]65707580[5090]GluProGluAspPheAlaValTyrTyrCysGinGinTyrGlyThrSer[5091]859095[5092]ProSerArgThrPheGlyProGlyThrLysValGlulieLysArg[5093]100105110[5094]SequenceID391[5095]ThrMetGlyPheThrAlaProArgPheProHisTyr[5096]1510[5097]SequenceID392[5098]MetGinSerProPheThrProHisPheAlaGluArg[5099]1510[5100]SequenceID393[5101]MetGinSerProlieValLeuProLeuSerLeuSer[5102]1510[5103]SequenceID394[5104]HisHisGluProGlyAlaTrpLeuProLeuSerPro[5105]1510[5106]SequenceID395[5107]gggggaggcttggcacagcctggggggtccctgagactctcctgtgcagcctctggattc60[5108]acctttagcagccatggcatgagctgggtccgccaggctccagggaaggggctggagtgg120[5109]gtctcagctattagtgggagtggtggtaacacttactacgcagactccgtgaagggccgg180[5110]ttcaccatctccagagacatttccaagaacacgctgtatctgcaaatgaacagcctgaga240[5111]gccgaagacacggccctatattactgtgcgagagggggcgcctatggttcggggagttat300[5112]aagtactggggccagggaaccctggtctccgtctcctcagcctccaccaagggcccatcg360[5113]gtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgc420[5114]ctggtcaaggactacttccccgaaccggtgacggtgtc458[5115]SequenceID396[5116]GlyGlyGlyLeuAlaGinProGlyGlySerLeuArgLeuSerCysAla[5117]151015[5118]AlaSerGlyPheThrPheSerSerHisGlyMetSerTrpValArgGin[5119]202530[5120]AlaProGlyLysGlyLeuGluTrpValSerAlalieSerGlySerGly[5121]3540455122]5123]5124]5125]5126]5127]5128]5129]5130]5131]5132]5133]5134]5135]5136]5137]5138]5139]5140]5141]5142]5143]5144]5145]5146]5147]5148]5149]5150]5151]5152]5153]5154]5155]5156]5157]5158]5159]5160]GlyAsn50AspArg65AlaSerSerLysGluGlyAlaThrlieAspSerSer115ThrSer130PheProTyrSerThrTyr100ThrSerGluTyrAlaLysTyr14SequenceID397Ala85LysLysGlyProAsn70LeuTyrGlyGlyVal5150Asp55ThrTyrTrpProSerLeuTyrGlySer120AlaValTyrCysGin105ValLysGlyLeuAla90GlyThr135ThrValPheAlaLeuGin75ArgThrProGlyArg60MetGlyLeuLeuCys140PheAsnGlyValThrSerAlaSer110ProlieSerLeuAla125LeuValTyr95ValSerLysArg80GlySerSerAsptggcacagcctggggggtccctgagactctcctgtgcagcctctggattc60gccatggcatgagctgggtccgccaggctccagggaaggggctggagtgg120ttagtgggagtggtggtaacacttactacgcagactccgtgaagggccgg180ccagagacatttccaagaacacgctgtatctgcaaatgaacagcctgaga240cggccctatattactgtgcgagagggggcgcctatggttcggggagttat300gccagggaaccctggtcaccgtctcctcagcctccaccaagggcccatcg360tggcaccctcctccaagagcacctctgggggcacagcggccctgggctgc420actacttccccgaaccggtgacggtgtc458SequenceIDGlyGlyGly398Leu1AlaAlaGlyArg65AlaSerSerSerProAsn50AspGluGlyAlaGlyPhe20LysGly35ThrlieAspSerSerTyrSerThrAla5ThrGlyTyrLysAla85LysTyr100ThrLysGinPheLeuAlaAsn70LeuTyrGlyProSerGluAsp55ThrTyrTrpProGlyGlySerTrp40SerLeuTyrGlySerHis25ValValTyrCysSer10GlySerLysLeuAla90GlyGin105ValPheLeuMetAlaGlyGin75ArgThrProArgSerlieArg60MetGlyLeuLeuLeuSerTrpSer45PheAsnGlyValAlaVal30GlyThrSerAlaCys15ArgSerlieLeuTyr95ValThr110ProSerAlaGinGlySerArg80GlySerSer5161]1151205162]LysSerThrSerGlyGlyThrAlaAlaLeuGly5163]1301355164]TyrPheProGluProValThrVal5165]1451505166]SequenceID3995175]5176]5177]5178]5179]5180]5181]5182]5183]5184]5185]5186]5187]5188]5189]5190]5191]5192]5193]5194]5195]5196]5197]5198]5199]125CysLeuValLysAsp1405167]gggggaggcgtggtccagcctgggaggtccctgagactctcctgtgcagcctctggattc605168]accttcagtagctatgacatgcactgggtccgccaggctccaggcaaggggctggagtgg1205169]gtggcaattatattggatgatggaagtaataaatactatgcagcctccgtgaagggccga1805170]ttcaccatctccagagacaacgccaagaactccctgcatctgcaaatgagcagcctgaga2405171]gccgaggacacggccctatattactgtgcgagagacctcccatatgctagtggccttgac3005172]tactggggacagggaaccctggtcaccgtctcgtcaccctccaccaagggcccatcggtc3605173]ttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctg4205174]gtcaaggactacttccccgaaccggtgacggtgtc455SequenceIDGlyGlyGly400Val1AlaSerGlyPhe20LysVal5ThrGinProGlyArgPheSerSerSerLeuArgLeuSer10AspMetHisTrpAlaProGly35LysSerAsn50ArgAsp65AlaAsnAspGluSerGlyLeuTyrAlaThrAsp100LysGlyLeuGluTyrAlaLysTrp40SerTyr25ValAlalielieValLysGlyAsn70AlaLeu85TyrTrpAlaSerValLysGlyArg5560SerLeuHisLeuGinMetLeu45PheVal30AspCys15ArgAlaGinGlyAspThrlieSerTyrGlyTyrGinGin75ArgCysAla90ThrLeuProSerThr115SerGlyGlyThrSerThr130ProGluProGlyProSerGlyValGly105PheAla135ValVal120AlaLeuGlyCysAspLeuProValThrProLeuAlaSerSerLeuArg80AlaLeu140Pro125ValVal110SerTyr95SerSerSerLysLysAspTyrPheProGluProValThr145150SequenceID401gggggaggcgtggtccagcctgggaggtccctgagactctaccttcagtagctatgacatgcactgggtccgccaggctcgtggcaattatattggatgatggaagtaataaatactatgcctgtgcagcctctggattccaggcaaggggctggagtggcagcctccgtgaagggccga60120180ttcaccatctccagagacaattccaagaacacgctgtatcgctgaggacacggctgtgtattactgtgcgaaagtgcgaaaataagtcctactttgactcctggggccagggaaccctggaccaagggcccatcggtcttccccctggcaccctcctccagcggccctgggctgcctggtcaaggactacttccccgaacSequenceID402GinProGlyArgSerLeutgcaaatgaacagcctgaga240tagggaaggtcaataaggtc300tcaccgtctcctcagcctcc360agagcacctctgggggcaca420cggtgacggtgtc473GlyGlyGlyVal1AlaSerGVal5ThrPheSerSerAlaProGly35LysTyrTyrAlaPheThrPheSerSerTyr2025LysGlyLeuGluTrpValArgMetHisAlalielie10AspLeuSerTrpSerAsn50AspAsnSerLysTrp40SerValLysGlyArg65AlaGluAspThrValAsnLysVal100ValAla55ThrLeuTyrLeuAsn70ValTyrTyrCysAla85AsnLysSerTyrGin75LysLeuValThr115ProSerSerLysPhe105ThrAla90AspSerLeuAla130LeuValLysAspSerSerAlaSer120ThrSerLysGlySer135PheProGluProGlyGlyArg60MetValTrpProLeu45PheAsnArgGlySer125AlaVal30AspThrSerlieGin110ValCys15ArgAsplieLeuGly95GlyCysLeuValLysAspTyrPheProGluProVal145150155SequenceID403gggggaggcttggtcgagcctggagggtccctgagactctaccttcagtgactactacatgagttgggtccgccaggctcattgcatacattagtactggtagtagttacataaattatgttcaccatctccagaaacaacgccaagaactcactgtatcgtcgacgacacggccgtgtattactgtgcgagatcgacaccccctcgtcctctttgaccactggggccagggaaccctggaccaagggcccatcggtcttccccctggcaccctcctccagcggccctgggctgcctggtcaaggactacttccccgaacSequenceID404GlyGlyGlyLeuValGluProGlyGlySerLeu1510AlaThrGlyPheThrPheSerAspTyrTyrMetThr140ThrValPheAlaLeuAlaGinGlySerArg80LysThrProGlycctgtgaagccactggattc60ctgggaaggggctggaatgg120cagactctaagaagggccga180tgcaactgaacagcctgaga240agagtttcggggagttatta300tcaccgtctcctcagcctcc360agagcacctctgggggcaca420cggtgacggtgtc473ArgLeuSerCysGlu15SerTrpValArgGin161AlaProSerTyr50ArgAsn65ValGly35lieAsnAspAspGlyGluLeuLeuValThr115Pro20LysAsnAlaThrLeu100ValGlyLeuGluTyrAlaLysAsn70ValTrp40Ser25lieAlaAsp55SerLeuAla85ProLeuTyrValLeuSerSerAlaLysTyrLeuTyrCysTyrlieLysGlyArg60LeuSer45Phe30ThrGlySerThrlieSerSerSerLysLeuAla130LeuValLysAspPhe105SerThr120ThrSerAla90AspLysGlyGin75ArgSerAsnSerLeuThrGinHisTrpGlyArg80SerPhe95GlyThrSer135PheProGluProGlyGlyCysLeuValLysAspTyrPheProGluProVal145150155SequenceID405gggggaggcttggtacagcctggggggtccctgagactctaccttaatcaactatgccatgagctgggtccgccaggctcgtctcagttattagtggaactggtgttggcacatactacgttcaccatctccagagacgattccaacaacacggtggatcgccgaggacacggccgtatattactgtgcgaaagatttcctctctaggctattggggccagggaatcctggtcaccgtcgccatcggtcttccccctggcaccctcctccaagagcacctggctgcctggtcaaggactacttccccgaaccggtgacggSequenceID406GlyGlyGlyLeuGin110ProSerValPhePro125ThrAlaAlaLeuGly140ThrValcctgtgcagcctctggatcc60cagggaaggggctggagtgg120cagactccgtgaggggccgg180tgcaaatgaatagcctgaga240aagtcttcggtgactacatt300cctcagcctccaccaagggc360ctgggggcacagcggccctg420tgtc4641AlaAlaProValGly50ArgAsp65AlaGluSerGlySer20LysGly35ThrTyrValGinPro5ThrLeulieLeuGluGlyGlyAsnAspAspThrGlyTyrAlaSerAsnTrp40SerTyr25ValSerLeuArgLeuSerCys1015AlaMetSerTrpValArgAla85Asn70ValAsp55ThrValValAspLeuTyrTyrCysAla90SerVallieArgGlyArg60GinMet75LysAspSer45PheVal30GlyAlaGinGlyThrThrlieSerAsnSerLeuPheGinVal95Arg80PheGlyAspTyrlieSerLeuGlyTyrTrpGlyGin100105ValAlaSerAlaSerThrLysGlyProSerVal115120SerSerLysSerThrSerGlyGlyThrAlaAla130135LysAspTyrPheProGluProValThrVal145150SequenceID407ggcccaggactggtgaagccttcggggaccctgtccctcatccatcagcagtagtaactggtggatttgggtccgccagctggattggagaaatcgatcatagtgggactaccaactacagtcaccatgtcagtggtcaagtccaagaaccagttctcccgccgcggacacggccgtctattactgtgcgagaggagcaatactggggccagggaatcttggtcaccgtctcctcagcctttccccctggcaccctcctccaagagcacctctgggggcagtcaaggactacttccccgaaccggtgacggtgtcSequenceID408GlyProGlyLeu1ValGinGlyVal65AlaTrpAlaSerSerProThr50ValAlaGlySerGlyGly20GlyPro35ThrLysAspPheThr115ThrSer130ProGluPhe145SequenceIDAsnSerThrAsp100LysGlyPro409Val5SerLysTyrLysAla85TyrGlyGlyValLyslieArgAsnAsn70ValTrpProThrThr150ProSerLeuPro55GinTyrGlySerAla135ValSerSerGlu40SerPheTyrGinGlyThr10AsnSer25TrpLeuSerCysGly105ValPhe120AlaLeulieLysLeuAla90lieProGlyGlylieLeuValThr110PheProLeuAlaPro125LeuGlyCysLeuVal140cctgcgctgtctctggtggc60ccccagggaagaggctggag120acccgtccctcaagagtcga180tgaagctgagctctgtgacc240aggataactggggattcgac300ccaccaagggcccatcggtc360cagcggccctgggctgcctg420455LeuTrpGlySerLys75ArgLeuLeuCysSerTrpGluArg60LeuGlyValAlaLeu140LeuThrlielie45ValSerAlaThrPro125ValTrp30AspThrSerLysVal110SerSerLysAspCys15ValHisMetValAsp95SerAlaArgSerSerThr80AsnSerLysTyr163[5317]ggcccaggactggtgaagccttcggggaccctgtccctcacctgcgctgtctctggtggc60tccatcagcagtagtaactggtggattttggtccgccagcccccagggaagaggctggag120tggattggagaaatcgatcatagtgggact3-CC3-3.Ct3.C3.acccgtccctcaagagtcga180gtcaccatgtcagtggtcaagtccaagaaccagttctccctgaagctgagctctgtgacc240gccgcggacacggccgtctattactgtgcgagaggagcaaaggataactggggattcgac300tactggggccagggaatcttggtcaccgtctcctcagcctccaccaagggcccatcggtc360ttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctg420gtcaaggactacttccccgaaccggtgacggtgtc455SequenceID410GlyProGlyLeuValLysProSerGlyThrLeuSerLeuThrCysAla151015ValSerGlyGlySerlieSerSerSerAsnTrpTrplieLeuValArgGinProGlyThr50ValVal65AlaAla2025GlyLysArgLeuGluTrp40SerLeuLysSerPro35ThrAsnLysAspThrLysTyrAsnSerLyslieGlyGlulie45ValAsn70AlaVal85TyrTrpProSerLeuLysSerArg5560GinPheSerLeuLysLeu30AspHisSerThrMetSerLys75ArgSerSerValTrpGlyPheAsp100AlaSerThrLysGlyProSer115TyrTyrCysAla90GlyGinGlylieLeuVal120Gly105PheGlyValProLeuAlaAlaLysThrPro125Val110SerAsp95SerThr80AsnSerSerLysSerThrSerGlyGlyThrAlaAla:LeuGlyCysLeuValLysAspTyr[5343]130135140[5344]PheProGluProValThrVal[5345]145150[5346]SequenceID411[5347]ggcccaggactggtgaagccttcggggaccctgtccctcacctgcgctgtctctggtggc60[5348]tccatcagcagtagtaactggtggatttgggtccgccagcccccagggaagaggctggag120[5349]tggattggagaaatcgatcatagtgggact3-CC3-3.Ct3.C3.acccgtccctcaagagtcga180[5350]gtcaccatgtcagtggtcaagtccaagaaccagttctccctgaagctgagctctgtgacc240[5351]gccgcggacacggccgtctattactgtgcgagaggagcaaaggataactggggattcgac300[5352]tactggggccagggaaccctggtctccgtctcctcagcctccaccaagggcccatcggtc360[5353]ttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctg420[5354]gtcaaggactacttccccgaaccggtgacggtgtc455[5355]SequenceID412164Gly1ValGinGlyVal65AlaTrpAlaSerProSerProThr50ValAlaGlySerGlyLeuGlyPro35ThrLysAspPheThr115ThrSer130ProGluGly20GlyAsnSerThrAsp100LysGlyProPhe145SequenceID413Val5SerLysTyrLysAla85TyrGlyGlyValLyslieArgAsnAsn70ValTrpProThrProSerLeuPro55GinTyrGlySerSerSerGlu40SerPheTyrGinGlyThr10AsnAla135ThrVal150Ser25TrpLeuSerCysGly105ValPhe120AlaLeulieLysLeuAla90ThrProGlyLeuTrpGlySerLys75ArgLeuLeuCysSerTrpGluArg60LeuGlyValAlaLeu140LeuThrlielie45ValSerAlaSerPro125ValTrp30AspThrSerLysVal110SerSerLysAspCys15ValHisMetValAsp95SerAlaArgSerSerThr80AsnSerLysTyrgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggatcc60[5378]accttaatcaactatgccatgagctgggtccgccaggctccagggaaggggctggagtgg120[5379]gtctcagttattagtggaactggtgttggcacatactacgcagactccgtgaggggccga180[5380]ttcaccatctccagagacaacgccaagaactcactgtctctgcaaacgaacagcctgaga240[5381]gccgaggacacggctgtctattattgcgttagattgtatagcagtggctgggacggctac300[5382]ttctatggactggacgtctggggccaagggaccacggtcaccgtctcctcagcctccacc360[5383]aagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcg420[5384]gccctgggctgcctggtcaaggactacttccccgaaccggtgacggtgtc470SequenceIDGlyGlyGly1AlaSerGlyAlaProGly35ValGlyThr50ArgAspAsn414LeuSer20LysTyrAlaVal5ThrGlyTyrLysGinLeuLeuAlaAsnProGlyGlylieGluAsp55SerAsnTyr25TrpVal40SerValSer10AlaSerArgLeuSerLeuLeuMetValGlyGinArgSerlieArg60ThrLeuSerTrpSer45PheVal30GlyThrAsnSerCys15ArgThrlieLeuAlaGinGlySerArg65AlaTrpValAlaGluAspThrPro130ValAspThrGlyVal115SerTyr100SerAla85Phe70ValTyrSerAlaSerTyrTyrCysGlyLeuAsp105LysVal90Val75ArgLeuTyrSerTrpGlyGin80SerGly95ThrThrSerLysLysAspTyrSerThr135ProGluProThr120SerGlyGlyThrGlyProSerGlyValLeuValLysAspTyrPheProGluProValThr145150155SequenceID415ggggctgaggtgaagaagactgggtcctcagtgaaggtgtagcttcacccagcgtttcctgcactgggtgcgacaggcccatggggtggatcacacctttcagtggaaatacctactacgctcaccattacgggggacaggtctgtgagtacagcctacatctgacgacacagccatctattactgtgtgatttttggtcaccctggtcaccgtctcctcagcctccaccaagggcccattcctccaagagcacctctgggggcacagcggccctgggctcccgaaccggtgacggtgtcSequenceID416LysAla140ValGly110ValPheProLeu125AlaLeuGlyCyscctgcatggtctccggaaac60ccggacaagcgcttgagtgg120cacagaaattccaggacaga180tggagttgagcagcctgaga240ttgactactggggcaaggga300cggtcttccccctggcaccc360gcctggtcaaggactacttc420440GlyAla1ValSerAlaProGlyGluValGlyAsn20GinLys5SerGly65SerAsn50AspGly35ThrTyrAspTrpGlyArgAspThrLysGly100PheAlaTyrAlaSerValThrPheThrLeuGluGlySerGinSer70lieGin55ThrAla85ThrLeuTyrValProLeuAlaProSerVal115ThrAlaAlaLeuGlyCys130Leu135Trp40LysAlaTyrThrPro120ValArg25MetSerValLysValSer10PheLeuHisTrpGlyPheGinTyrMetCysVal105SerVal90SerTrpAspGlu75lieVal30lieThrPro45LeuThrArg60LeuCysMet15ArgGinPheSerlieThrPheGlyLeuSerAlaSerSerSerLeuArg80TyrAsp95LysSerLysLysAspTyrSerThr125PhePro140Thr110SerGlyGlyGlyGluProVal[5435]ThrVal145SequenceID417ggggcrgaggtgaagaagacagcttcacccagcgtttcctatggggtggatcacacctttctcaccattacgggggacagtctgacgacacagccatctaaccctggtcaccgtctcctctcctccaagagcacctctggcccgaaccggtgacggtgtcSequenceID418GlyAlaGluValtgggtcctcagtgaaggtgtgcactgggtgcgacaggccccagtggaaatacctactacggtctgtgagtacagcctacattactgtgtgattttcggtcagcctccaccaagggcccatgggcacagcggccctgggctcctgcatggtccggacaagccacagaaatttggagttgagttgactactgcggtcttcccgcctggtcaactccggaaacgcttgagtggccaggacagacagcctgagagggcaagggacctggcacccggactacttc1ValSerGlyAsn20GinAlaLeuGluLysLysThrGlySerSerVal510SerPheThrGinArgPheLeuAlaProGly35ThrTyrTyrAlaGlyAsn50GlyAsp65SerAspTrpGlyArgSerValAspThrLysGin55ThrAlaArg25TrpMetGly40LysPheGinTrpAspSer70AlalieTyrTyr85ThrLeuValThrProSerVal115Gly100PheProLeuAlaPro120TyrCysVal105SerMetGlu75lieLysHislieArg60LeuValSerTrpVal90SerSerPheAlaSerLysSerThr45LeuSerGlySerThr125Val30ProThrSerLeuCys15ArgPhelieLeuAsp95LysThr110SerGlyMetGinSerThrArg80TyrGlyGly60120180240300360420440ThrAlaAlaLeuGlyCysLeuVal:LysAspTyrPheProGluProVal[5463]130135140[5464]ThrVal[5465]145[5466]SequenceID419[5467]ggggctgactttaagaagcctggggcctcagcgagggtctcctgcaaggcatcgggatac60[5468]accttcaccaactactacttccactgggtacgacaggcccctggacaagggcttgagtgg120[5469]atgggaataatcaaccctgttggtgaaactagagtcaatacagagaagttccgggacaga180[5470]gtcaccatgaccagggacacgtccacgaacacagtctacatggacctgagcagcctgaga240[5471]tctgaggatacggccgtctattattgtgcgaggtcatattattatgcttcggggagtcct300[5472]gaggaggacgatgcttttgatatctggggccaggggtcaatggtcatcgtctcttcagcc360ccaagagcacctctgggggcaaccggtgacggtgtctccaccaagggcccatcggtcttccccctggcaccctcctacagcggccctgggctgcctggtcaaggactacttccccgSequenceID420LysProGlyAlaSerAlaArgValSerGlyAla1AlaSerAlaProGluAspPheGlyTyr20GinLys5ThrPheArg65SerThr50AspGly35ArgValGluSerGlySerThrAspThrGlyAsnThrSerThrThrAsnLeuGluPro100lieAsn70AlaVal85GluGluTrp40GluLys55ThrValTyr25Met10TyrGlyPheArgPheHisTrplielieAspTyrAspTyrAspTyrCysArg60LeuAsn45ValVal30ProCys15ArgLysGinValGlyThrMetThrMetAsp75ArgSerAla90PheSerSerLeuArg80AlaSerMetVal115AlaProSerSerProLeu130GlyCysLeuValLys145SequenceID421ValSerSerAla120SerAla105SerThrAspLysThrSerGlylieGlyTyrTyrTrpAsp150Lys135TyrPheProGluPro125ThrPro155Gly140ValThrGly110SerAlaValTyr95GinGlyPheValAlaLeuSequenceID422GlyAlaGluValArgLysProGlyAlaSerVal1510AlaSerAlaTyrThrLeuThrAspTyrTyrMet2025ThrProGlyGinGlyLeuGluTrpMetGlylie3540ArgValSerCysArg15HisTrpValArgGin30lieAsnProSerGly45420476ggggctgaggtgaggaagcctggggcctcagtgagggtttcctgcagggcatctgcatac60[5498]accctcacagactactatatgcactgggtgcgacagacccctggacaagggcttgaatgg120[5499]atgggaataatcaaccctagtggtggtagcacaacctacgcacagaagttccagggcaga180[5500]gtcaccatgaccagggacacgtccaccagcacagtctacatggacctgagcagcctgaga240[5501]tctgaagacacggccgtgtattactgtgctaggtctgactacggacacttcgtgcaacac300[5502]tcctacttctacggtatggacgtctggggccaagggaccacggtcaccgtctcctcagcc360[5503]tccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggc420[5504]acagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacggtgtc476168GlySer50AspArg65SerPheThrProGluValThrLeu130ThrThrAspGinVal115AlaThrSerThrTyrThrAla85SerAlaGin55ThrSer70ValHis100ThrValTyrSerProSerSerTyrPheSerLys135LysValTyrTyrAla120SerPheTyrCysGinGlyMetAla90MetAsp75ArgGly105SerThrAspLysThrSerGlyArg60LeuSerValGlyGly140ValSerAspTrpPro125ThrThrSerTyrGly110SerMetThrLeuGly95GinValAlaAlaArg80HisGlyPheLeuGlyCysLeuValLysAspTyrPheProGluProValThrVal[5525]145150155[5526]SequenceID423[5527]gggggaggcttgctcaagccaggagggtccctgagactctcctgtgtagcctctggattc60[5528]agcataagcgacttctacatgagttggatccgccaggctccagggaaaggactggagtgg120[5529]atctcatacctcagtggtggcagtacttacaggagccacgcagactctgggaagggccga180[5530]ttcaccatctccagagacaacgccaagaattcactgtttttgcaaatgagtagcctggga240[5531]gtcgaggacacggccgtgtatttttgtgcgaggcatgtgggagtggcgactgcctttgat300[5532]atctggggccaagggacagtggtcactgtctcctcagcctccaccaagggcccatcggtc360[5533]ttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctg420[5534]gtcaaggactacttccccgaaccggtgacggtgtc455[5535]SequenceID424[5536]GlyGlyGlyLeuLeuLysProGlyGlySerLeuArgLeuSerCysVal1AlaAlaProThrSerGlyPhe20LysArg65ValThrAlaTyr50AspGluAlaSerGly35ArgAsnAspPheThrSerAlaThr5SerGlyHisLysAla85lieAsp100LysGlylieLeuAlaAsn70ValTrpProSerGluAsp55SerTyrGlySerAspPhe25lie10TyrMetSerTrpTrp40SerLeuPheGinValGlyPheCysSerLysLeuAla90ThrTyrLeuGlyGly105PheProGin75ArgValLeuArg60MetHisValAlaSer45PheSerValThrProlie30GlyThrSerGly15ArgGinGlySerlieSerLeuGly80ValAla95SerVal110SerSerSerLys169115120SerThrSerGlyGlyThrAlaAlaLeuGlyCys130135PheProGluProValThrVal145150SequenceID425125LeuValLysAspTyr140ggcccaggggtggtgaagccttcggagaccctgtccctcacctgcattgtctccggtgac60[5558]tccatgaccagttattactgggcctggctccggcagtcgtcagggaagggactggagtgg120[5559]attggatatgccttcaatacgaggaatgacgagtatagtccctccttcaggggtcgagcc180[5560]accatatcggtggacgcgtccaagagtcaggtctccctgcacttgacctctgtgacctct240[5561]gtggacacggccgtgtacttttgtgcgagactcccttactctatcaattactttgacttc300[5562]tggggccagggaaccgttgtcaccgtgtcctcagcctccaccaagggcccatcggtcttc360[5563]cccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctggtc420[5564]aaggactacttccccgaaccggtgacggtgtc452SequenceIDGlyPro1ValSerGlyGly426ValValLysProSerGluThrLeuSerLeuThr5SerMetSerSerGly35AsnAspGlu50AlaSerAsp65ValAspTyrPheSerThrThrSer130GluThrAspLys115GlyAsp20LysGlyLeuTyrSerProLysSerAlaThrSerGluGin70TyrSer55ValTrp40PheTyr25lieThr10TyrGlyArgGlyTrpTyrArgAlaTrpAlaSerLeuHisAla60ThrPhe45ThrLeu30AsnCys15ArgPhe100GlyVal85TrpGlyPheGinProSerValCysGlyAlaArg90ThrVal105ProLeuLeu75LeuProlieSerValThrlieGinThrArgSerValGlyProValThrAlaThrAla135Phe120LeuGlyCysLeuValAlaProTyrThrValSer80AsnSerlie95SerAlaSer110SerVal140Ser125LysAspLysSerTyrPheProGluProValThrVal145150SequenceID427ggaggaggcttggtcaagcctggcgggtccctgagactctactttcagtaacggctggatgagctgggtccgccaggctcgtcggccggattagaagcaaccccgacggtggcacaacagcctgcacagcctctggattcctgggaaggggctggagtggactacgctgcacccttcaaa60120180170[5590]ggcagattcaccatctcaagagatgattcaaaaaatacattgtttctgcaagtgaccagc240[5591]ctgaaaaccgaggacacaggcgtctattactgcatcacagatcggggtgactggaagtgg300[5592]ggggtccctagggacctcacctactggggccagggaaccctggtcaccgtctcctcagcc360[5593]tccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggc420[5594]acagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacggtgtc476[5595]SequenceID428[5596]GlyGlyGlyLeuValLysProGlyGlySetLeuArgLeuSetCysThr[5597]l5lo15[5598]AlaSetGlyPheThrPheSetAsnGlyTrpMetSetTrpValArgGln[5599]202530[5600]AlaProGlyLysGlyLeuGluTrpValGlyArgIleArgSetAsnPro[5601]354045[5602]AspGlyGlyThrThrAspTyrAlaAlaProPheLysGlyArgPheThr[5603]505560[5604]IleSetArgAspAspSetLysAsnThrLeuPheLeuGlnValThrSet[5605]65707580[5606]LeuLysThrGluAspThrGlyValTyrTyrCysIleThrAspArgGly[5607]859095[5608]AspTrpLysTrpGlyValProArgAspLeuThrTyrTrpGlyGlnGly[5609]100105110[5610]ThrLeuValThrValSetSetAlaSetThrLysGlyProSetValPhe[561]]115120125[5612]ProLeuAlaProSetSetLysSetThrSetGlyGlyThrAlaAlaLeu[5613]130135140[5614]GlyCysLeuValLysAspTyrPheProGluProValThrVal[5615]145150155[5616]SequenceID429[5617]gccatgatcgagctcacccagtctccagactccctggctgtgtctctgggcgagagggcc60[5618]accatcaactgcaagtccagccagagtattttatacagctccaacagtcagaactactta120[5619]gcttggtaccagcagaaaccaggacagcctcctaagctgctcatttactgggcatctacc180[5620]cgggaatccggggtccctgaccgattcagtggcagcgggtctgggacagatttcactctc240[5621]accatcagcagcctgcaggctgaagatgtggcagtttattactgtcagcattattatagt300[5622]actcctccgtgggcgttcggccaggggaccaaggtggaaatcaaacgaactgtggctgca360[5623]ccatctgtcttcatcttcccgccatctgatga392[5624]SequenceID430[5625]AlaMetIleGluLeuThrGlnSetProAspSetLeuAlaValSetLeu[5626]l5lo15[5627]216[5628]GlyGluArgAlaThrIleAsnCysLysSetSetGlnSetIleLeuTyr[5629]SerSerAsn35GinProPro50ProAsp20SerGinAsnTyrVal65ThrLysArgPheLeu40Tyr25AlaLeuLeulie55GlySerlieSerSerHisTyrTyrGlulieSer70GinLeu85ThrProProTrpTrpGlySerAlaGluAspTrpAlaSerTyrGinGin45Arg30LysProLys115Ser100ArgThrValAlaAla120Ala105ProVal90PheGly75AlaGlySerValThr60ThrValGinPheAspTyrTyrGlyGluPheThrGlySerGlyLeu80GinCys95LysVallie125Thr110PheProProSerAsp130SequenceID431agctcactcagtctccagactccctggctgtgtctctgggcgagagggcc60gcaagtccagccagagtgttttatacacctccaacaataggaaccactta120agcagaaaccaggacagcctcctaaactgctcatttactgggcatctacc180gggtccctgaccgattcagtggcagcgggtctgggacagatttcactctc240gcctgcaggctgaagatgtggcagtttattactgtcagcattattatagt300gggcgttcggccaggggaccaaggtggatttcaaacgaactgtggctgca360tcatcttcccgccatctgatga392SequenceIDAlaMetAla1GlyThrGinVal65ThrHisAspGluArgSerPro50ProlieTyrPheAsn35ProAspSerTyrLys432GluAla20AsnLysArgSerLeu5ThrArgLeuPheLeu85SerThr100ArgThrThrlieAsnLeuSer70GinProValGinAsnHislie55GlyAlaProAlaSerProCysLeu40TyrSerGluTrpAlaLys25AlaTrpGlyAspAsp10SerTrpAlaSerVal90PheAla105ProSerSerSerTyrSerGly75AlaGlyValLeuGinGinThr60ThrValGinPheAlaValSerGin45ArgAspTyrGlylieVal30LysGluPheTyrSer15LeuProSerThrCys95LysThr110PheProLeuTyrGlyGlyLeu80GinValPro172[5668[5669[5670[5671[5672[5673[5674[5675[5676[5677[5678[5679[5680[5681[5682[5683[5684[5685[5686[5687[5688[5689[5690[5691[5692[5693[5694[5695[5696[5697[5698[5699[5700[5701[5702[5703[5704[5705[5706115SerAsp130SequenceID433gccatggccgagctcacgcaaccctctcctgcggggccagagacctggcctggcgcccagccggacaggttcagtggcaggagcctgaagattttgcagtggccgggggaccagactggacgccatctgagSequenceID434AlaMetAlaGlu120125gtctccagccatcctgtctttcagagtgttcccagcaaccgctcctcgtctatgattctttgggtctggaacagccttcaatattactgtcaacagtacggttcaaacgaactgtggctgtgtctccaggtcttagcctgccagcagggcctctcaccatgttactcacccaccatctgtagagagagccgtaccagcagcactggcatccagcagaatgtctgacttttcttcatctcc1GlyGluArgAsnLeuLeu35LeuValTyr50GlySerAla20AlaTrpTyrGinThrGinSerProAlalie10AlaSerLeu5ThrLeuSerCysGly25ArgProSer65GluProGluAspAspSerSerGlySerGin40ArgAlaThrSer55ThrAlaPheThrGly70AlaValTyrTyrPhe85GlyArgGlyThrProLeuThrPhe100SerValPhelieCys90LeuArg105ArgHisLeuGlyGlyLeu75GinGinGluPheLeuGinLeulie60ThrSerLeuSerAla45ProlieTyrLysVal30ProAspSerGlyArg110Ser15ProArgArgArgProSerLeuPheMet80SerTyr95ThrValAlaAlaProSerValPhelieSer115120SequenceID435gccatggccgagctcacgcagtctccaggcaccctatctgaccctctcctgtagggccagtcagagtgtcgacagcaactaaacctggccaggctcccaggctcctcatttatggtgcgtccagacaggttcagtggcagtgggtctgggacagacttcagagcctgaggattttgtcgtgtattactgtcagcagtatcggccaagggacacgaSequenceID436AlaMetAlaGluLeuThrGinSerProGlyThr1510GlyAspArgAlaThrLeuSerCysArgAlaSertgtctccaggggatagagccacttagcctggttccagcagatagcagggccactggcatcctctcaccatcagcagactgttagcccgccgatcaccttcLeuSerValSerPro15GinSerValAspSer60120180240300360371601201802403003151735707]5708]5709]5710]5711]5712]5713]5714]5715]5716]5717]5718]5719]5720]5721]5722]5723]5724]5725]5726]5727]5728]5729]5730]5731]5732]5733]5734]5735]5736]5737]5738]5739]5740]5741]5742]5743]5744]5745]AsnTyrLeu35lieTyrGlySer20AlaLeu50Ser65GluTrpAlaProGluProlieThrGlyGlySerAspPhe85GlyPheGinGin40SerArg25LysProGly30ProTyr55Gly70ValThrValGinGlyAlaPheAspTyrTyrThrThrThrCys90Gly60Leu75GinSequenceIDAlaMetAla1GlyAsnLeuSer65GluProAlaGluArgTyrlie50GlyProlieAlaLeu35TyrSerGluThr438GluAla20AlaGlyGlyAspLeu5ThrTrpAlaSerPhe85GlyPhe100SerValThrLeuPheTyrGly70ValGinPheGinSerGinSer55ThrValGlylieSerProCysGin40ArgAspTyrThrArg25LysAlaPheTyrArg105ProProSerValPheliePhe115120SequenceID439gccatggccgagctcacgcagtctccaggcaccctgtctttccctctcctgcagggccagtcagactgttctcagcaattAla45ProAspGinlieThrlieSerGinTyrLeuArgLeuArgPheArgLeu80SerPro95PheGlyGinGlyThrArg100105SequenceID437gccatggccgagctcacgcagtctccagacaccctgtcttaccctctcctgtagggccagtcagagtgtcgacagcaactaagcctggccaggctcccaggctcctcatttatggtgcgtccagacaggttcagtggcagtgggtctgggacagacttcagagcctgaggattttgtcgtgtattactgtcagcagtatcggccaagggacacgactggagactaaacgaactgtggctgccgccatctgatgatgtctccaggggaaagagcc60acttagcctggttccagcag120atagcagggccactggcatc180ctctcaccatcagcagactg240ttagcccgccgatcaccttc300caccatctgtcttcatcttc360374Asp10AlaProThrThrCys90LeuGluProSerThrSerGlyGlyLeu75GinLeuGinGinlie60ThrGinThrAspSerLeuSerAla45ProlieTyrLysVal30ProAspSerLeuArg110Ser15AspArgArgArgProSerLeuPheLeu80ProSer95ThrValtgtctccaggggaaacagtcacttagcctggtaccagcag60120174[5746]aaacctggccaggctcccagggtcctcctctatggtgcatctagcagggccactggcatc180[5747]ccagacaggttcagtggcggtgggtctgggacagacttcactctaaccatcagcagactg240[5748]gagcctgaagattttgcagtgtattactgtcagcaatatgttagttcaccgtggacgttc300[5749]ggccaagggaccaaggtggaattcaaacgaactgtggctgcaccatctgtcttcatcttc360[5750]ccgccatctgatga374[5751]SequenceID440[5752]AlaMetAlaGluLeuThrGinSerProGlyThrLeuSerLeuSerPro[5753]151015[5754]GlyGluThrValSerLeuSerCysArgAlaSerGinThrValLeuSer[5755]202530[5756]AsnTyrLeuAlaTrpTyrGinGinLysProGlyGinAlaProArgVal[5757]354045[5758]LeuLeuTyrGlyAlaSerSerArgAlaThrGlylieProAspArgPhe[5759]505560[5760]SerGlyGlyGlySerGlyThrAspPheThrLeuThrlieSerArgLeu[5761]65707580[5762]GluProGluAspPheAlaValTyrTyrCysGinGinTyrValSerSer[5763]859095[5764]ProTrpThrPheGlyGinGlyThrLysValGluPheLysArgThrVal[5765]100105110[5766]AlaAlaProSerValPheliePheProProSerAsp[5767]115120[5768]SequenceID441[5769]gccatggccgagctcacgcagtctccaggcaccctgtctttgtctccaggggaaagagcc60[5770]accctctcctgcagggccagtcagagcattcgcagcaacttcttagcctggtaccagcag120[5771]aaacctggccaggctcccaggctcctcatctttggtgcatcgaacagggccactggcatc180[5772]ccagacaggttcagtggcagtgggtctgggacagacttcactctcaccatcagtagactg240[5773]gagcctgaagattttgcggtttattactgtcagcagtatagtagctcaccggacactttt300[5774]ggccaggggaccaagctggagatcaaacgaactgtggctgcaccatctgtcttcatcttc360[5775]ccgccatctgatga374[5776]SequenceID442[5777]AlaMetAlaGluLeuThrGinSerProGlyThrLeuSerLeuSerPro[5778]151015[5779]GlyGluArgAlaThrLeuSerCysArgAlaSerGinSerlieArgSer[5780]202530[5781]AsnPheLeuAlaTrpTyrGinGinLysProGlyGinAlaProArgLeu[5782]354045[5783]LeuliePheGlyAlaSerAsnArgAlaThrGlylieProAspArgPhe[5784]505560SerGlySerGlySerGlyThrAspPheThrLeu657075GluProGluAspPheAlaValTyrTyrCysGin8590ProAspThrPheGlyGinGlyThrLysLeuGlu100105AlaAlaProSerValPheliePheProProSer115120SequenceID443gccatggccgagctcacgcagtctccaggcaccctgtcttaccctctcctgcagggccagccagagcgttagtagcaactaaacctggccaggctcccaggctcctcatctatggtgcatccagacaggttcagtggcagtgggtctgggaccgacttcagagcctgaagattttgcagtttattactgtcaacattatgttcggccctgggaccaaagtggatgtcaaacgaactgtggttcccgccatctgatgaThrlieSerArgLeu80GinTyrSerSerSer95lieLysArgThrVal110AsptgtctccaggggaaagagtcacttaacctggtaccagcagccagaagggccactggcatcctctcaccataagcagactggtagctcacctccattccctctgcaccatctgtcttcatcSequenceIDAlaMetAla1GlyGluArgAsnTyrLeu35LeulieTyr50SerGlySer65GluProGluProProPhe444GluVal20ThrThrGinSerProGlyThrLeuSerLeu10AlaSerLeu5ThrLeuSerCysGlyGlySerAspTrpAlaSerTyrGinGin40ArgArg55ThrArg25LysProPro100ProPhe85PheGly70AlaValAlaPheGlySerValPheAspTyrTyrProGlyThrThrCys90LysGlyGlyGinSerGinVal30ProSerPro15SerSerLeu75Ginlie60ThrAla45ProAsplieHisTyrGlyValAspValArgLeuArgPheSerArglie120ValAlaAla115SequenceID445gccatggccgagctcacacagtctccagacaccctgtctcaccctctcttgcagggccagtgagagtattgatgggagaccagcctggccaggctcccaggctcctcatttatgatgtttccatacaggttcagaggcagtgggtctgggacagacttcagagcctgaagattttgcagtctactactgtcaacattatgThrLysValAspValLys105110PheProProSerLeu80SerSer95ArgThrAsp12560120180240300360377tgccaccaggggaaagggcc60gcttggcctggtaccagcag120ccaggagggccattggcgtc180ctctcaccatcggtggactg240gtttctcagtgtacactttg300[5824]gccaggggaccaggctgcgtcccacgaactgtggctgcaccatctgtcttcatcttcccgccatctga446ThrGinSerProAspThrLeuSerLeu360368SequenceIDAlaMetAlaGlu1GlyGluArgArgArgLeu35LeulieTyr50ArgGlySer65GluProGluTyrThrAla20AlaLeu5ThrLeuSerCysAspGlySerAspTrpValSerTyrGinGin40Arg10ArgAla25GinProSerGluSerGinValAlaProLeu100ValPhe85AlaGly70AlaArg55ThrAlaPheArgPhelieValGlyProPheAspTyrTyrlieThrGlyGlyVal60ThrAla45Prolie30ProLeu75GinHisGly105ProCys90CysValProSerTyrlieGlyGlyTyrArgThr110ProPro15AspGlyArgLeuArgPheGlyLeu80PheSer95ValAlaSerValPheliePhePro115120SequenceID447gccatggccgagctcacccagtctccatcctccctgtctgaccatcacttgccgggcaagtcaggacattagaaatgattccagggagagcccctaatctcctgatctatggtgcatccatttaggttcagcggcagtggatctggctcagatttcactccctgaagattttgcaacttattactgtctacaagatcacacaggggaccagggtggaaatcaaacgaactgtggctgcacccatctgatgacatctgtaggagacagagtctaagctggtatcagcagaaagtttacagaggggggtcccatcaccatcagcagcctgcagattaccctctaacgttcggccatctgtcttcatcttcccgSequenceIDAlaMetAla448Glu1GlyAsplieAspLeuTyr50SerArgVal20TrpGly65ProGluSer35GlyGlyAspAlaSerPheLeu5ThrTyrSerGlyAlaThrlieGinSerSer70ThrGinThrGinLeu55AspSerProCysLys40GinPheTyrTyrArg25ProArgThrCysSer10AlaGlyGlyLeuLeuSerSerArgValLeuGinAlaPro60lieSerAlaAspThr75GinAspPro45PheSerHislie30AsnArgSerAsnSer15ArgLeuPheLeuTyrValAsnLeuSerGin80Pro601201802403003603711778590LeuThrPheGlyGinGlyThrArgValGlulie100105AlaProSerValPheliePheProProSerAsp115120SequenceID449gccatggccgagctcacccagtctccatcctccctgtctgaccgtcacttgccgggcaagtcagaccattgccaactattccagggaaagcccctaacctcctgatccaagctgcttccatcaaggttcagtggcagtcgatctgggacagatttcactccctgaggattttgcaacttacttctgtcaacagagtttcacaagggaccaaagtggaaatcaaacgaactgtggctgcacccatctgatga95LysArgThrValAla110catctgtaggtaaattggtactttgcaaggtcaccatcacgcgccccctgcatctgtcttagacagagtctcagcaaaaatggggtcccacagtctgcaggacgttcggccatcttcccgSequenceIDAlaMetAla1GlyAspArg450GluLeuThrGinSerPro5ThrValThrCysVal20TrpTyrGinGinTyrLeuAsnTrpTyrGinGinLys3540AlaAlaSerThrLeuGinArg25ProSer10AlalieGin50GlySer65ProGluGlyGlyGlyValSerLeuSerGinLysAlaSerAlaThrLeu55AspPheThrLeuArgSerGlyThr70AspPheAlaThrTyrPheCysTrpThrPheAla85GinGlyThrLysGly100ValPheliePheVal105ProGin90GluThr75GinPro60lieSerlieLysPro45SerThrPheArglie30AsnArgSerSerThr110Ser15AlaLeuPheLeuValAsnLeuSerGin80ProAla95ValAlaSerAspAlaProSerValPheliePhePro115120SequenceID451gccatggccgagctcacccagtctccatcctccctgtctgaccatcacttgccggtcaagtcagaacattaacatctactccagggagagcccctaaactcctgatctatgctacatccatcaaggttcagtggcagtggatctgggacagacttcactccctgaagattttgcaacttactactgtcaacagagttacagggaccaagSequenceID452AlaMetAlaGluLeuThrGinSerProSerSercatctgttggagacagagtctaagttggtatcaacagaaaatttgcaaagtggggtcccatcaccatcagcagtctgcaagtgacccgacgttcggccaaLeuSerAlaSerVal60120180240300360371601201802403003091781GlyAspArg5ThrTyrLeulieSer35AlaVal20TrpTyrlieGinThrSerAsnGly65Tyr50SerGlySerGlyThrCysGinLys40GinArg25Pro10SerGlySerGlySerGinAsnAla15AsnlieThr70Leu55AspPheThrLeuArgValThr75lie30LysLeuLeuPro60liePro45SerArgPheSerSerSerLeuGin80ProGluAspPheAlaThrTyrTyrCysGinGinSerTyrSerAspPro[5912]859095[5913]ThrPheGlyGinGlyThrLys[5914]100[5915]SequenceID453[5916]accctcacctgccgggcaagtctgagcattagttactttttaaattggtatcagcagaaa60[5917]ccaggtaaagcccctaagctcctgatctatgctgcatcccgtttgcacagtggggtccca120[5918]tcaaggttcagtggcagtgggtctgggacagaattcactctcaccatcagcagtttgcaa180[5919]cctgaagatcttgcaacttactactgtcaacagagttacggtactcctgggactttcggc240[5920]cctgggaccaaagcggccttcaaacgaactgtggctgcaccatctgtcttcatcttcccg300[5921]ccatctgatga311SequenceIDThrLeuThr1TyrGinGinSerArg454CysLys20HisArg5ProGlyThr50AlaThr65ProGlyPhelieLeu35GluPheThrLeuAlaSerLeuSerGlyLysAlaSerGlyVallieSerTyr10LysLeuLeuTyrThrPheTyrLysPro100CysGin70AlaThr55GinPro40liePro25SerArgPheSerPheLeulieAla85ProPheSerAspSerTyrLysArgSerSerLeuGin60ProGly45ProGlyThr75ThrValAla90Tyr30SerGluThrAsn15AlaTrpAlaGlyAlaProGlySerAspLeuPheSer95Gly80Val179權(quán)利要求分離的多聚核苷酸分子，其包含1-389和395-453奇數(shù)號(hào)SequenceID中任意一種或其片段，并編碼包含2-390和396-454中偶數(shù)號(hào)SequenceID中任意一種的氨基酸序列或其片段。2.包含2-390和396-454的偶數(shù)號(hào)SequenceID中任意一種的氨基酸序列或任何同源序列或任何帶有保守取代的序列，其結(jié)合于在冠狀動(dòng)脈斑塊中可能發(fā)現(xiàn)的抗原或其任何片段。3.權(quán)利要求2的且對(duì)應(yīng)于SequenceIDn°22、38、44、52及54的分離的氨基酸序列。4.權(quán)利要求2的氨基酸序列，其具有至少80%，優(yōu)選地至少90%，更優(yōu)選地至少95%，甚至更優(yōu)選地至少97%的種系同源性；或其任何片段。5.權(quán)利要求2或3的氨基酸序列，其⑶R3部分的p-值低于5%，優(yōu)選地低于2%，更優(yōu)選地低于1%，甚至更優(yōu)選地低于1%。，或其任何片段。6.由權(quán)利要求1中多聚核苷酸分子編碼的權(quán)利要求2-5的氨基酸序列或其任何片段。7.包含一種或多種權(quán)利要求1的分離的多聚核苷酸分子的表達(dá)載體。8.權(quán)利要求7的表達(dá)載體，其包含SequenceIDn°53以及，可選地，任意一種SequenceIDn°21、37、43和51中所述的序列。9.權(quán)利要求7或8的表達(dá)載體，其選自質(zhì)粒、粘粒、YAC、病毒顆粒或噬菌體。10.包含權(quán)利要求7中一種或多種表達(dá)載體的表達(dá)系統(tǒng)。11.包含權(quán)利要求10的表達(dá)系統(tǒng)的分離的重組宿主細(xì)胞。12.權(quán)利要求11的分離的重組宿主細(xì)胞，其選自原核重組分離細(xì)胞如腸桿菌屬，埃希氏菌屬，歐文式菌屬，克雷伯菌屬，變形菌屬，沙門氏菌屬，沙雷氏菌屬和志賀氏菌屬，桿菌屬，假單胞菌屬和鏈霉菌屬；優(yōu)選地所述的原核重組分離細(xì)胞選自大腸桿菌，鼠傷寒沙門氏菌，粘質(zhì)沙雷氏菌，枯草芽孢桿菌，地衣芽孢桿菌，銅綠假單胞菌；甚至更優(yōu)選地所述的原核重組分離宿主細(xì)胞為大腸桿菌XLl-Blue；酵母重組宿主細(xì)胞如酵母屬，巴斯德畢赤酵母，或克魯維酵母屬如乳酸克魯維酵母、脆壁克魯維酵母、保加利亞克魯維酵母、魏氏克魯維酵母、瓦爾特克魯維酵母、果蠅克魯維酵母、耐熱克魯維酵母和馬克斯克魯維酵母，裂殖酵母屬如粟酒裂殖酵母，子囊酵母屬，漢森酵母屬，里氏木霉，粗糙鏈孢霉，許旺酵母屬如西方許旺酵母，鏈孢霉屬，青霉屬，彎頸霉，曲霉屬如構(gòu)巢曲霉，假絲酵母屬，球擬酵母屬和紅酵母屬；優(yōu)選地所述酵母重組宿主細(xì)胞為釀酒酵母；人重組的分離的宿主細(xì)胞如中國(guó)倉(cāng)鼠卵巢(CH0)，SV40轉(zhuǎn)化的猴腎CVI細(xì)胞系(C0S-7，ATCCCRL1651)，人胚腎細(xì)胞系，中國(guó)倉(cāng)鼠卵巢細(xì)胞/-DHFR，小鼠支持細(xì)胞，人肺細(xì)胞(W138，ATCCCCL75)；人肝細(xì)胞(HepG2，HB8065)；和小鼠乳腺腫瘤(MMT060562，ATCCCCL51)；植物分離的重組宿主細(xì)胞如根癌農(nóng)桿菌和煙草；昆蟲重組的分離的細(xì)胞，如果蠅S2和夜蛾Sf9。13.制備重組抗體或其任何片段的方法，其包括步驟a)制備包括表達(dá)載體以及包含所述表達(dá)載體的宿主細(xì)胞表達(dá)系統(tǒng)，所述表達(dá)載體包含一種或多種對(duì)應(yīng)于任意一種權(quán)利要求1的多聚核苷酸序列的多聚核苷酸分子；b)在合適的生長(zhǎng)條件下培養(yǎng)所述的宿主細(xì)胞；c)回收這樣生產(chǎn)的抗體或其任何片段；以及d)純化所述抗體或其任何片段。14.權(quán)利要求13的方法，其中步驟a)的一種或多種多聚核苷酸分子選自1-389和395-453的SequenceID的奇數(shù)號(hào)序列。15.權(quán)利要求13或14的方法，其中重組的分離的宿主細(xì)胞選自大腸桿菌、枯草芽孢桿菌、釀酒酵母或中國(guó)倉(cāng)鼠卵巢(CHO)。16.權(quán)利要求13-15中任何一項(xiàng)的方法，其用于制備IgG抗體或其任何片段。17.權(quán)利要求13-15中任何一項(xiàng)的方法，其用于制備IgG抗體Fab片段。18.權(quán)利要求13-15的方法生產(chǎn)的重組的分離的抗體或其任何片段。19.據(jù)權(quán)利要求13-15的方法生產(chǎn)的重組IgG抗體或其任何片段。20.據(jù)權(quán)利要求13-15的方法生產(chǎn)的重組IgGFab片段。21.據(jù)權(quán)利要求13-16的方法生產(chǎn)的，并包含SequenceIDn°22、38、44、52和54中任意一種所示的氨基酸序列的重組的分離的IgGFab片段。22.權(quán)利要求13-16進(jìn)一步生產(chǎn)的權(quán)利要求21的重組的分離的IgGFab片段。23.權(quán)利要求21的重組的分離的IgGFab片段，其結(jié)合于在冠狀動(dòng)脈斑塊中可能存在的抗原。24.治療組合物，其包含權(quán)利要求18-23中任何一項(xiàng)的重組抗體或其任何片段，可選地包含治療部分。25.權(quán)利要求24的治療組合物，其中治療部分選自放射性核素、藥物和前藥、激素、激素拮抗物、受體拮抗物、酶或另一種試劑激活的酶原、自分泌因子或細(xì)胞因子、抗微生物試劑和毒素。26.診斷組合物，其包含權(quán)利要求18-23中任何一項(xiàng)的重組抗體或其任何片段和診斷部分。27.權(quán)利要求24或25的治療組合物，其用于治療急性冠狀動(dòng)脈綜合征(ACS)。28.權(quán)利要求26的治療組合物，其用于診斷急性冠狀動(dòng)脈綜合征(ACS)。29.結(jié)合于權(quán)利要求2-6中任何一項(xiàng)的氨基酸序列的配體。30.結(jié)合于權(quán)利要求18-23中任何一項(xiàng)的重組抗體或其任何片段的配體。31.包含氨基酸共有序列且結(jié)合于權(quán)利要求18-23中任何一項(xiàng)的重組抗體或其任何片段的肽。32.權(quán)利要求31的肽，其具有對(duì)應(yīng)于391-394的SequenceID的氨基酸。33.權(quán)利要求29的配體，其通過(guò)包括使用權(quán)利要求2-6的分離的氨基酸序列的方法而選擇。34.權(quán)利要求30的配體，其通過(guò)包括使用權(quán)利要求18-23的重組抗體的方法而選擇。35.用于鑒定結(jié)合于權(quán)利要求18-23中任何一項(xiàng)權(quán)利要求的重組抗體或其任何片段的配體的方法，所述方法包括步驟a)將所述抗體或其任何片段結(jié)合于固相上；b)通過(guò)一個(gè)或多個(gè)洗滌步驟移除未結(jié)合的物質(zhì)；c)將候選分子與步驟a)中制備的固相接觸，并允許候選分子和固相孵育一段合適的時(shí)間；d)通過(guò)一個(gè)或多個(gè)洗滌步驟移除未結(jié)合的物質(zhì)；e)加入特異于步驟a)的抗體復(fù)合物的第二抗體，所述抗體復(fù)合物具有結(jié)合于其上的候選分子；以及f)鑒定步驟a)的抗體上所結(jié)合的分子。36.權(quán)利要求35的方法，其中步驟a)的抗體或其片段為權(quán)利要求18-23的抗體或其片段。37.用于鑒定結(jié)合于權(quán)利要求2-6中任何一項(xiàng)的氨基酸序列；或其任何片段的配體的方法，所述方法包括步驟a)將所述的氨基酸序列或其任何片段結(jié)合于固相上；b)通過(guò)一個(gè)或多個(gè)洗滌步驟移除未結(jié)合的物質(zhì)；c)將候選分子與步驟a)中制備的固相接觸，并允許候選分子和固相孵育一段合適的時(shí)間；d)通過(guò)一個(gè)或多個(gè)洗滌步驟移除未結(jié)合的物質(zhì)；e)加入特異于步驟a)的氨基酸序列復(fù)合物的第二抗體，所述氨基酸序列復(fù)合物具有結(jié)合于其上的候選分子；以及f)鑒定步驟a)上所結(jié)合的分子。38.權(quán)利要求36的方法，其中步驟a)的氨基酸序列或其任何片段為權(quán)利要求2-6的氨基酸序列或其任何片段。39.離體或體外診斷方法，其包括將選自全血，血清和冠狀動(dòng)脈斑塊片段的樣品與權(quán)利要求19-23中任何一項(xiàng)的抗體或其任何片段接觸的步驟。40.權(quán)利要求39的離體或體外診斷方法，其用于診斷患者中急性冠狀動(dòng)脈綜合征(ACS)。41.權(quán)利要求39的離體或體外診斷方法，其用于篩選具有急性冠狀動(dòng)脈綜合征(ACS)風(fēng)險(xiǎn)的群體。全文摘要提供了用于制備抗體或其片段的方法，使用包含編碼所述抗體或其片段的DNA序列的原核宿主細(xì)胞，其中所述DNA序列衍生自冠狀動(dòng)脈斑塊樣品。還提供了包含所述抗體的組合物。也描述了針對(duì)所述抗體的配體及含有所述配體的組合物。文檔編號(hào)C07K16/18GK101855243SQ200880115497公開日2010年10月6日申請(qǐng)日期2008年9月18日優(yōu)先權(quán)日2007年9月20日發(fā)明者M(jìn)·克萊門蒂,R·布廖尼申請(qǐng)人:伯拉考成像股份公司