專利名稱:原鈣粘著蛋白蛋白質(zhì)及其應(yīng)用的制作方法
本申請(qǐng)是1993年12月23日提交的國際專利申請(qǐng)No.PCT/US93/12588的后續(xù)部分,前者本身又是1992年12月29日提交的美國專利申請(qǐng)序號(hào)No.07/998,003的后續(xù)部分。
發(fā)明的領(lǐng)域本申請(qǐng)總地涉及與細(xì)胞-細(xì)胞粘著相關(guān)的材料和方法。更具體地說,本發(fā)明涉及稱為原鈣粘著蛋白的新的粘著蛋白質(zhì),和編碼原鈣粘著蛋白的多核苷酸序列。本發(fā)明還涉及抑制原鈣粘著蛋白與其天然配體/抗配體結(jié)合的方法。
發(fā)明的背景在體內(nèi),細(xì)胞間粘著在形態(tài)發(fā)生和器官形成、白細(xì)胞外侵、腫瘤轉(zhuǎn)移和侵染,以及細(xì)胞接合的形成等過程中起著重要作用。此外,細(xì)胞-細(xì)胞粘著對(duì)于組織整合性的維持是很關(guān)鍵的。
細(xì)胞間粘著是由特異性細(xì)胞表面粘著分子介導(dǎo)的。已將細(xì)胞粘著分子分為至少四個(gè)家族,其中包括免疫球蛋白超家族、整聯(lián)蛋白超家族、選擇蛋白超家族和鈣粘著蛋白超家族。所有形成實(shí)體組織的細(xì)胞類型均表達(dá)鈣粘著蛋白超家族的某些成員,此提示鈣粘著蛋白參予大多數(shù)細(xì)胞類型的選擇性粘著。
已將鈣粘著蛋白總地描述為糖基化整合膜蛋白質(zhì),其具有由以鈣粘著蛋白所獨(dú)有的序列為特征的5個(gè)亞區(qū)域組成的N末端細(xì)胞外區(qū)域(似乎直接參予結(jié)合的是該區(qū)域的N末端113個(gè)氨基酸)、疏水跨膜區(qū)域及通過連環(huán)蛋白及其他細(xì)胞骨架相關(guān)蛋白質(zhì)與細(xì)胞骨架作用的C末端胞漿區(qū)域。但某些鈣粘著蛋白缺少胞漿區(qū)域并且似乎通過與具有胞漿區(qū)域之鈣粘著蛋白不同機(jī)制在細(xì)胞-細(xì)胞粘著中發(fā)揮功能。在具有胞漿區(qū)域的鈣粘著蛋白中,胞漿區(qū)域是細(xì)胞外區(qū)域的粘著功能所必需的。在不同細(xì)胞上表達(dá)的鈣粘著蛋白家族成員之間的結(jié)合是同嗜性的(即鈣粘著蛋白家族的成員與其自身的鈣粘著蛋白或密切相關(guān)的亞類結(jié)合)和Ca2+依賴性的。有關(guān)鈣粘著蛋白的最新綜述可參見Takeichi,Annu.Rev.Biochem.,59237-252(1990)和Takeichi,Science,2511451-1455(1991)。
已根據(jù)其參予Ca2+依賴性細(xì)胞粘著和其獨(dú)特的免疫學(xué)特性及組織定位鑒定了將要描述的第一類鈣粘著蛋白(小鼠上皮細(xì)胞中的E-鈣粘著蛋白、鳥肝臟中的L-CAM、小鼠胚泡中的桑椹胚粘著蛋白,及人上皮細(xì)胞中的CAM120/80)。隨著后來對(duì)N-鈣粘著蛋白的免疫學(xué)鑒定,發(fā)現(xiàn)其具有與E-鈣粘著蛋白不同的組織分布,已發(fā)現(xiàn)了一個(gè)Ca2+依賴性細(xì)胞-細(xì)胞粘著分子的新家族這一事實(shí)變得更加明確了。
編碼E-鈣粘著蛋白(參見Nagafuchi et al.,Nature,329341-343(1987))、N-鈣粘著蛋白(Hatta et al.,J.Cell,Biol.,106873-881(1988)),和P-鈣粘著蛋白(Nose etal.,EMBO J.,63655-3661(1987))之基因的分子克隆為包括一個(gè)細(xì)胞粘著分子家族的鈣粘著蛋白提供了結(jié)構(gòu)證據(jù)。L-CAM(Gallin et al.,Proc.Natl.Acad.Sci USA,842808-2812(1987))和桑椹胚粘著蛋白(Ringwald et al.,EMBO J.,63647-3653(1986))的克隆則揭示了它們與E-鈣粘著蛋白是相同的。比較E-、N-和P-鈣粘著蛋白的氨基酸序列顯示這三個(gè)亞類間氨基酸相似性水平約為45-58%。Liaw等人(EMBO J.,92701-2708(1990))描述了使用基于E-、N-和P-鈣粘著蛋白之保守區(qū)域的簡(jiǎn)并寡核苷酸,以PCR方法從牛微血管上皮細(xì)胞cDNA擴(kuò)增N-和P-鈣粘著蛋白。
Suzuki et al.,Cell Regulation,2261-270(1991)中報(bào)導(dǎo)了用PCR技術(shù)分離另外八種鈣粘著蛋白。繼后,有人描述了包括R-鈣粘著蛋白(Inuzuka et al.,Neuron,769-79(1991))、M-鈣粘著蛋白(Donalies,Proc.Natl.Acad.SciUSA,888024-8028(1991))、B-鈣粘著蛋白(Napolitano,J.Cell Biol.,113893-905(1991))和T-鈣粘著蛋白(Ranscht,Neuron,7391-402(1991))在內(nèi)的其他幾種鈣粘著蛋白。
此外,還描述了顯然與鈣粘著蛋白相關(guān)的蛋白質(zhì)如橋粒芯蛋白(Goodwin et al.,Biochem.Biophys.Res.Commun.,1731224-1230(1990)和Koch et al.,Eur.J.Cell Biol.,531-12(1990))和橋粒膠粘蛋白(desmocollins)(Molton et al.,J.Cell Science,97239-246(1990))。這些分子的細(xì)胞外區(qū)域在結(jié)構(gòu)上與典型鈣粘著蛋白的細(xì)胞外區(qū)域相關(guān),但又各有獨(dú)特的胞漿區(qū)域。Mahoney等人(Cell,67853-868(1991))描述了稱為fat的,也編碼鈣粘著蛋白相關(guān)蛋白質(zhì)的果蠅屬腫瘤抑制基因。fat腫瘤抑制基因包括34個(gè)鈣粘著蛋白樣亞區(qū)域,然后是4個(gè)EGF樣重復(fù)區(qū)、跨膜區(qū)域、及一個(gè)新的胞漿區(qū)域。對(duì)這些鈣粘著蛋白相關(guān)蛋白質(zhì)的鑒定證明了一個(gè)以存在鈣粘著蛋白細(xì)胞外區(qū)域基序?yàn)樘卣鞯拇蟮某易濉?br>
有關(guān)各種鈣粘著蛋白相關(guān)蛋白質(zhì)之組織表達(dá)的研究揭示,各亞類分子均具有獨(dú)特的組織分布模式。例如,E-鈣粘著蛋白見于上皮細(xì)胞中,而N-鈣粘著蛋白則見于神經(jīng)和肌肉細(xì)胞中。因?yàn)閭€(gè)別蛋白質(zhì)在特定發(fā)育階段似乎是由特異細(xì)胞和組織表達(dá)的,所以鈣粘著蛋白相關(guān)蛋白質(zhì)的表達(dá)似乎也是空間的并且在發(fā)育期間受到暫時(shí)調(diào)節(jié)的(如參見Takeichi(1991),文獻(xiàn)出處同上)。鈣粘著蛋白相關(guān)蛋白質(zhì)的異位表達(dá)和對(duì)鈣粘著蛋白相關(guān)蛋白質(zhì)固有表達(dá)的抑制阻止了正常組織結(jié)構(gòu)的形成(Detrick et al.,Neuron,4493-506(1990);Fujimori et al.,Development,110;97-104(1990);Kintner,Cell,69225-236(1992))。
當(dāng)考慮到蛋白質(zhì)的各個(gè)亞類可能在體內(nèi)正常生理過程(如小腸上皮細(xì)胞屏障的維持)和異常病理過程(如腫瘤轉(zhuǎn)移或炎癥)中發(fā)揮作用時(shí),不同的鈣粘著蛋白和鈣粘著蛋白相關(guān)蛋白質(zhì)的獨(dú)特的暫時(shí)和組織表達(dá)特征是特別重要的。鈣粘著蛋白相關(guān)蛋白質(zhì)的不同亞類或亞類組合很可能負(fù)責(zé)其中可期望進(jìn)行治療檢測(cè)和/或干預(yù)的不同的細(xì)胞-細(xì)胞粘著作用。例如,尋常天皰瘡(一種由于缺少細(xì)胞粘著能力而引起的以水皰形成為特征的自身免疫性皮膚病)病人的自身抗體可與對(duì)鈣粘著蛋白的體內(nèi)粘著功能提供直接支持的鈣粘著蛋白相關(guān)蛋白質(zhì)反應(yīng)(Amagai et al.,Cell,67869-877(1991))。研究還顯示,鈣粘著蛋白和鈣粘著蛋白相關(guān)蛋白質(zhì)除有粘著活性外,還可能有調(diào)節(jié)功能。據(jù)Matsunaga等人報(bào)導(dǎo)(Nature,33462-64(1988)),N-鈣粘著蛋白具有軸突過度生長(zhǎng)促進(jìn)活性。果蠅fat腫瘤抑制基因似乎可如哺乳動(dòng)物E-鈣粘著蛋白一樣調(diào)節(jié)細(xì)胞生長(zhǎng)并抑制腫瘤侵染(參見Mahoney et al.,文獻(xiàn)同上;Frixen et al.,J.Cell.Biol.,113173-185(1991);Chen et al.,J.Cell.Biol.,114319-327(1991);Vleminckx et al.,Cell,66107-119(1991))。因此,可以期望對(duì)在特定組織中表達(dá)的鈣粘著蛋白相關(guān)蛋白質(zhì)的調(diào)節(jié)活性進(jìn)行治療干預(yù)。
因此本領(lǐng)域仍要求鑒定并定性那些參與細(xì)胞-細(xì)胞粘著和/或調(diào)節(jié)過程的其他鈣粘著蛋白相關(guān)蛋白質(zhì)。此外,鈣粘著蛋白相關(guān)蛋白質(zhì)可在一定程度上形成開發(fā)治療和診斷劑的基礎(chǔ),而克隆編碼這些蛋白質(zhì)的基因是必要的。有關(guān)編碼鈣粘著蛋白相關(guān)蛋白質(zhì)之DNA序列及氨基酸序列的資料將得以用重組技術(shù)大批量生產(chǎn)這些蛋白質(zhì),并得以鑒定天然產(chǎn)生這些蛋白質(zhì)的組織/細(xì)胞。這些序列資料也將允許制備與鈣粘著蛋白相關(guān)蛋白質(zhì)發(fā)生特異反應(yīng)的抗體物質(zhì)或其他新的結(jié)合分子,這些物質(zhì)或分子則可用于調(diào)節(jié)所說的蛋白質(zhì)參予的天然配體/抗配體結(jié)合反應(yīng)。
發(fā)明的概要本發(fā)明提供與鈣粘著蛋白相關(guān)的材料及與細(xì)胞-細(xì)胞粘著相關(guān)的方法。一個(gè)方面,本發(fā)明提供純化的和分離的編碼新的細(xì)胞粘著分子的多核苷酸(如可以是正義和反義鏈的DNA和RNA),所說的新的細(xì)胞粘著分子本文中稱為原鈣粘著蛋白并包括原鈣粘著蛋白-42、原鈣粘著蛋白-43、原鈣粘著蛋白pc3、原鈣粘著蛋白pc4和原鈣粘著蛋白pc5。本發(fā)明優(yōu)選的多核苷酸序列包括基因組和cDNA序列以及完全或部分合成的DNA序列,及其生物學(xué)復(fù)制品(即體外制得的序列的拷貝)。還期望提供包含這些多核苷酸序列的生物學(xué)活性載體。
本發(fā)明的特別舉例的原鈣粘著蛋白多核苷酸序列是質(zhì)粒pRC/RSV-pc42和pRC/RSV-pc43中的插入片段,所說的質(zhì)粒已于1992年12月16日保存于美國典型培養(yǎng)物保藏中心(ATCC,12301ParklawnDrive,Rockville,Maryland 20852),ATCC保藏登記號(hào)分別為No.69162和69163。
通過公開本發(fā)明的DNA和氨基酸序列所提供的信息的科學(xué)價(jià)值是明顯的。例如,編碼原鈣粘著蛋白的部分或完整DNA的序列知識(shí)有可能以標(biāo)準(zhǔn)DNA/DNA雜交或PCR技術(shù)分離編碼該蛋白質(zhì)(或其變異體)的全長(zhǎng)cDNA或基因組DNA序列,并且就基因組DNA序列來說,還可分離用于指定原鈣粘著蛋白特異性調(diào)節(jié)序列如啟動(dòng)子、增強(qiáng)子等的基因組DNA序列?;蛘撸捎贸R?guī)技術(shù)化學(xué)合成本發(fā)明的DNA序列。雜交和PCR技術(shù)也允許分離編碼與本文特別舉例的原鈣粘著蛋白同源之異源原鈣粘著蛋白的DNA。
根據(jù)本發(fā)明的另一個(gè)方面,宿主細(xì)胞,特別是真核和原核細(xì)胞,是以允許在細(xì)胞中表達(dá)原鈣粘著蛋白多肽的方式用本發(fā)明的多核苷酸序列穩(wěn)定轉(zhuǎn)化或轉(zhuǎn)染的。當(dāng)表達(dá)原鈣粘著蛋白多肽產(chǎn)物的宿主細(xì)胞生長(zhǎng)于適當(dāng)?shù)呐囵B(yǎng)基中時(shí),特別適于大批量產(chǎn)生原鈣粘著蛋白多肽、其片段及變異體,從而能夠從細(xì)胞中或從培養(yǎng)細(xì)胞的培養(yǎng)基中分離所需的多肽產(chǎn)物。
本發(fā)明的新的原鈣粘著蛋白產(chǎn)物可以作為分離物從天然組織來源的得到,但更好是以涉及本發(fā)明之宿主細(xì)胞的重組方法產(chǎn)生。這些產(chǎn)物可以依據(jù)所選用的宿主細(xì)胞或重組生產(chǎn)和/或分離后加工方法的不同,以完全或部分糖基化、部分或完全去糖基化、或非糖基化的形式得到。
根據(jù)本發(fā)明的原鈣粘著蛋白變異體可以包括其中缺失或被置換一個(gè)或多個(gè)特定氨基酸的多肽類似物,或其中加入了一個(gè)或多個(gè)非天然編碼之氨基酸的多肽類似物(1)沒有丟失,并且更好是提高了一種或多種原鈣粘著蛋白特異的生物學(xué)活性或免疫學(xué)性質(zhì);或者(2)特異性損害特定配體/抗配體結(jié)合功能。本發(fā)明還預(yù)期包括對(duì)本發(fā)明原鈣粘著蛋白特異的抗體物質(zhì)(如單克隆和多克隆抗體、嵌合和人源化抗體、包括Fab、Fab′、F(ab′)2、FV或單一可變區(qū)在內(nèi)的抗體區(qū)域,以及單鏈抗體)??墒褂梅蛛x的天然、重組或合成原鈣粘著蛋白多肽產(chǎn)物或在其表面上表達(dá)這些產(chǎn)物的宿主細(xì)胞開發(fā)抗體物質(zhì)??梢岳每贵w物質(zhì)純化本發(fā)明的原鈣粘著蛋白多肽、檢測(cè)多肽的組織表達(dá)及作為原鈣粘著蛋白之配體/抗配體結(jié)合活性的拮抗劑。本發(fā)明特別舉例說明的單克隆抗體是由定名為38I2C的雜交瘤細(xì)胞系產(chǎn)生的原鈣粘著蛋白-43特異性單克隆抗體,所說的雜交瘤細(xì)胞系于1992年12月2日保存于ATCC,入藏登記號(hào)為ATCC No.HB11207。
在參照附圖閱讀下面的詳細(xì)描述之后將會(huì)明確了解本發(fā)明的許多其他方面和優(yōu)點(diǎn),其中附
圖1A-C顯示了排成行的本發(fā)明原鈣粘著蛋白氨基酸序列與N-鈣粘著蛋白和果蠅fat腫瘤抑制基因的氨基酸序列。
發(fā)明的詳細(xì)描述以下述實(shí)施例舉例說明本發(fā)明,其中實(shí)施例1、2和3描述用PCR技術(shù)分離原鈣粘著蛋白多核苷酸序列。實(shí)施例3還描述本發(fā)明的幾種原鈣粘著蛋白基因的染色體定位。實(shí)施例4描述用DNA/DNA雜交技術(shù)分離本發(fā)明的其他原鈣粘著蛋白多核苷酸序列。實(shí)施例5介紹包括編碼原鈣粘著蛋白-42或原鈣粘著蛋白-43之多核苷酸的表達(dá)質(zhì)粒的構(gòu)建以及用這些質(zhì)粒轉(zhuǎn)染L細(xì)胞的方法。實(shí)施例6描述抗原鈣粘著蛋白-42及原鈣粘著蛋白-43抗體的產(chǎn)生。實(shí)施例7介紹對(duì)表達(dá)原鈣粘著蛋白-42或原鈣粘著蛋白-43之被轉(zhuǎn)染的L細(xì)胞進(jìn)行免疫檢測(cè)的結(jié)果。實(shí)施例8描述了經(jīng)原鈣粘著蛋白-42、原鈣粘著蛋白-43或嵌合原鈣粘著蛋白-43/E-鈣粘著蛋白分子轉(zhuǎn)染的L細(xì)胞的細(xì)胞集合特性。實(shí)施例9描述了pc43的鈣結(jié)合性質(zhì)。實(shí)施例10、11和12分別說明以Northern印跡法、Western印跡法和原位雜交法檢測(cè)各種表達(dá)原鈣粘著蛋白-42和原鈣粘著蛋白-43之組織和細(xì)胞系的結(jié)果。實(shí)施例13描述鑒定與原鈣粘著蛋白-43共沉淀之120kDa蛋白質(zhì)的免疫沉淀實(shí)驗(yàn)。
實(shí)施例1使用聚合酶鏈反應(yīng)(PCR)分離編碼鈣粘著蛋白相關(guān)多肽的新的大鼠cDNA片段。
PCR引物的設(shè)計(jì)將已公布的L-CAM(Gallin et al.,文獻(xiàn)同上)、E-鈣粘著蛋白(Nagafuchi et al.,文獻(xiàn)同上)、小鼠P-鈣粘著蛋白(Nose et al.,文獻(xiàn)同上)、桑椹胚粘著蛋白(Ringwald etal.,文獻(xiàn)同上)、雞N-鈣粘著蛋白(Hatta et al.,文獻(xiàn)同上)、小鼠N-鈣粘著蛋白(Miyatani et al.,Science,245631-635(1989))和人P-鈣粘著蛋白(Shimoyama et al.,J.Cell.Biol.1091787-1794(1989))的氨基酸序列進(jìn)行比較,以鑒定保守氨基酸序列的兩個(gè)區(qū)域一個(gè)來自鈣粘著蛋白細(xì)胞外第三亞區(qū)域(EC-3)的中部,另一個(gè)來自細(xì)胞外第四亞區(qū)域(EC-4)的C末端,并設(shè)計(jì)分別在下面列出的以IUPAC-IUB生物化學(xué)命名法命名的相應(yīng)簡(jiǎn)并寡核苷酸,以用作PCR引物。
引物1(SEQ ID NO1)5′AARSSNNTNGAYTRY6A 3′引物2(SEQ ID NO2)3′TTRCTRTTRCGNGGNNN 5′使用Applied Biosystems 380B型DNA合成儀(Foster City,California)合成簡(jiǎn)并寡核苷酸。
經(jīng)PCR克隆cDNA序列基于大鼠腦cDNA制劑,以與Suzuki等人(Cell Regulation,2261-270(1991))所述者相似的方法進(jìn)行PCR。用Maniatis等人(Molecular CloningA Laboratory Manual,pp.196,ColdSpring Harbor,New YorkCold Spring Harbor Laboratory(1982))所述的異硫氰酸鈲/氯化銫方法從大鼠腦中制備總RNA。然后使用FastTrack試劑盒(Invitrogen,San Diego,California),分離腦poly(A)+RNAs并使用cDNA合成試劑盒(BoehringerMannheim Biochemicals,Indianapolis,Indiana)制備cDNA。向100ng模板cDNA和10μg各引物中加入2.5單位Taq DNA聚合酶(Boehringer Mannheim Biochemicals)以開始PCR反應(yīng),然后進(jìn)行35次反應(yīng)循環(huán)94℃變性1.5分鐘、45℃退火2分鐘、72C聚合3分鐘。對(duì)PCR反應(yīng)產(chǎn)物進(jìn)行瓊脂糖凝膠電泳,發(fā)現(xiàn)大小約為450堿基對(duì)(bp)和130bp的兩條主帶。450bp帶相當(dāng)于兩個(gè)引物位點(diǎn)之間所期望的長(zhǎng)度,這兩個(gè)引物位點(diǎn)分別對(duì)應(yīng)于鈣粘著蛋白細(xì)胞外第三亞區(qū)域(EC-3)的中部和鈣粘著蛋白細(xì)胞外第四亞區(qū)域(EC-4)的羧基末端;但130bp帶則不能從以前鑒定的任何鈣粘著蛋白序列推斷出來。用凍融法提取450bp和130bp帶。用T4多核苷酸激酶使所得片段在5′末端磷酸化并以序列分析的平端連接法平端連接到M13mp18(Boehringer Mannheim Biochemicals)的SmaI位點(diǎn),以進(jìn)行亞克隆。使用Sequenase試劑盒(United States Biochemicals,Cleveland,Ohio)以二脫氧核苷酸鏈終止法測(cè)定片段的序列。使用Beckman Microgenie程序(Fullerton,California)分析DNA和氨基酸序列。
cDNA序列的分析分離19個(gè)新的部分cDNA克隆??寺〉腄NA序列和由之推測(cè)的氨基酸序列(包括相當(dāng)于PCR引物的序列)如下所示RAT-123(分別為SEQ ID Nos3和4)、RAT-212(SEQ ID NOs5和6),RAT-214(SEQ ID NOs7和8),RAT-216(SEQ ID NOs9和10),RAT-218(SEQ ID NOs11和12),RAT-224(SEQ ID NOs13和14),RAT-312(SEQ ID NOs15和16),RAT-313(SEQ ID NOs17和18),RAT-314(SEQ ID NOs19和20),RAT-315(SEQ ID NOs21和22),RAT-316(SEQ ID NOs23和24),RAT-317(SEQID NOs25和26),RAT-321(SEQ ID NOs27和28),RAT-323(SEQ IDNOs29和30),RAT-336(SEQ ID NOs31和32),RAT-352(SEQ ID NOs33和34),RAT-411(SEQ ID NOs35和36),RAT-413(SEQID NOs37和38),和RAT-551(SEQ ID NOs39和40)。
推測(cè)的cDNA克隆的氨基酸序列與已知鈣粘著蛋白的序列同源但又不同。因此所描述的鈣粘著蛋白在細(xì)胞外第三亞區(qū)域(EC-3)中具有高度保守的、短的氨基酸序列,包括位于該亞區(qū)域之中間區(qū)的共有序列D-Y-E或D-F-E及在其末端的共有序列D-X-N-E-X-P-X-F(SEQ ID NO41)或D-X-D-E-X-P-X-F(SEQ ID NO42)(Hatta et al.,文獻(xiàn)同上)而除細(xì)胞外第五亞區(qū)域(EC-5)外的其他亞區(qū)域的相應(yīng)序列則分別是D-R-E和D-X-N-D-N-X-P-X-F(SEQ ID NO43)。相反,新克隆相當(dāng)于鈣粘著蛋白細(xì)胞外亞區(qū)域的推測(cè)的氨基酸序列則在一個(gè)末端包括序列D-Y-E或D-F-E,但在另一端則具有代替D-X-N-E-X-P-X-F或D-X-D-E-X-P-X-E的序列D-X-N-D-N-X-P-X-F。由部分克隆編碼的多肽是與以前鑒定的鈣粘著蛋白同源的,但與Genbank中的任何其他序列則沒有顯示明顯的同源性。因此,該部分cDNAs似乎包含鈣粘著蛋白相關(guān)分子的一個(gè)新的亞類。
實(shí)施例2結(jié)構(gòu)上與實(shí)施例1中所述的大鼠cDNAs相似的各種cDNA片段是使用實(shí)施例1中所述的引物1和2,以PCR方法從人、小鼠和非洲爪蟮腦cDNA制劑,以及從果蠅和C.elegans全身cDNA制劑中分離的。所得PCR片段的DNA序列和推測(cè)的氨基酸序列(包括相當(dāng)于PCR引物的序列)如下MOUSE-321(SEQ ID NOs44和45),MOUSE-322(SEQID NOs46和47)MOUSE-324(SEQ ID NOs48和49),MOUSE-326(SEQ ID NOs50和51),HUMAN-11(SEQ ID NOs52和53),HUMAN-13(SEQ ID NOs54和55),HUMAN-21(SEQ ID NOs56和57),HUMAN-24(SEQ ID NOs58和59),HUMAN-32(SEQ ID NOs60和61),HUMAN-42(SEQ ID NOs62和63),HUMAN-43(SEQ ID NOs64和65),HUMAN-212(SEQ ID NOs66和67),HUMAN-213(SEQ ID NOs68和69),HUMAN-215(SEQ ID NOs70和71),HUMAN-223(SEQ ID NOs72和73),HUMAN-410(SEQ ID NOs74和75),HUMAN-443(SEQ ID NOs76和77),XENOPUS-21(SEQ IDNOs78和79),XENOPUS-23(SEQ ID NOs80和81),XENOPUS-25(SEQID NOs82和83),XENOPUS-31(SEQ ID NOs84和85),DROSOPHILA-12(SEQ ID NOs86和87),DROSOPHILA-13(SEQ ID NOs88和89),DROSOPHILA-14(SEQ ID NOs90和91)和C.ELEGANS-41(SEQ IDNOs92和93)。比較所推測(cè)的氨基酸序列表明這些不同組克隆間有顯著的相似性。具體地說,有三組克隆似乎是種間同源的RAT-218、MOUSE-322和HUMAN-43;RAT-314、MOUSE-321和HUMAN-11;以及MOUSE-326和HUMAN-42。
實(shí)施例3為了確定由PCR產(chǎn)物限定的新蛋白質(zhì)的完整結(jié)構(gòu),分離兩個(gè)相當(dāng)于部分cDNA HUMAN-42和HUMAN-43的全長(zhǎng)人cDNAs。
全長(zhǎng)人cDNAs的分離用32P標(biāo)記的HUMAN-42和HUMAN-43DNA片段,以噬斑雜交方法(Ausubel et al.,Eds.,Current Protocols in MolecularBiology,Sections 6.1.1-6.1.4和6.2.1-6.2.3,John Wiley& Sons,New York(1987))篩選入ZapII載體中的人胎腦cDNA文庫(Stratagene,La Jolla,California)。噬斑純化陽性克隆,并使用輔助病毒,以Bluescript SK(+)質(zhì)粒形式用體內(nèi)切除方法切掉插入段。然后將此插入段序列亞克隆到M13載體(BoehringerMannheim,Biochemicals)中進(jìn)行測(cè)序。用各含有兩個(gè)cDNAs的探針分離幾個(gè)重疊cDNA克隆,所說的cDNA含有兩種稱為原鈣粘著蛋白-42(pc42)和原鈣粘著蛋白-43(pc43)的兩種新蛋白質(zhì)之推測(cè)的完整編碼序列。SEQ ID NOs94和95中分別列出pc42的DNA及其推測(cè)的氨基酸序列,同時(shí)SEQ ID NOs96和97中則分別列出pc43的DNA及其推測(cè)的氨基酸序列。
Sano等人在優(yōu)先權(quán)申請(qǐng)之后,在The EMBO Journal,12(6)2249-2256(1993)中發(fā)表了本發(fā)明原鈣粘著蛋白序列的克隆方法。在1991年12月9日美國細(xì)胞生物學(xué)學(xué)會(huì)的會(huì)議上已提出了pc43的推測(cè)的氨基酸序列。報(bào)告的摘要是作為Suzuki et al.,J.Cell.Biol.,11572a(Abstract416)(December9,1991)發(fā)表的。
全長(zhǎng)人克隆的分析將pc42和pc43的全長(zhǎng)cDNA序列與原來以PCR方法得到的各種DNA片段的序列相比較,表明MOUSE-326和HUMAN-42相當(dāng)于pc42之細(xì)胞外第四亞區(qū)域(EC-4)的-部分,并且RAT-314、MOUSE-321,和HUMAN-11相當(dāng)于pc43之細(xì)胞外第三亞區(qū)域(EC-3)的一部分,而RAT-218、MOUSE-322和HUMAN-43則相當(dāng)于pc43之細(xì)胞外第五亞區(qū)域(EC-5)的一部分。
pc42和pc43的總體結(jié)構(gòu)與典型鈣粘著蛋白相似,但這些新的分子也有不同的特征。兩種原鈣粘著蛋白cDNA序列都含有推測(cè)的翻譯起始位點(diǎn)并且翻譯的氨基酸序列隨典型的信號(hào)序列開始,但這些克隆卻沒有存在于所有已知鈣粘著蛋白前體中的前序列。該cDNAs編碼具有一個(gè)大的N末端細(xì)胞外區(qū)域和一個(gè)由跨膜序列連接之相對(duì)短的C末端胞漿區(qū)域的蛋白質(zhì)。pc42和pc43的細(xì)胞外區(qū)域長(zhǎng)度不同,并且pc42含有七個(gè)很類似于典型鈣粘著蛋白細(xì)胞外亞區(qū)域的亞區(qū)域,而pc43有六個(gè)這樣的亞區(qū)域。原鈣粘著蛋白胞漿區(qū)域的大小相似于典型鈣粘著蛋白的相應(yīng)區(qū)域,但序列并沒有顯示與已知鈣粘著蛋白或鈣粘著蛋白相關(guān)蛋白質(zhì)的序列有明顯的同源性。
下列表1中給出了人pc42和pc43、以及小鼠N-鈣粘著蛋白(SEQID NO98)(作為“典型”鈣粘著蛋白的一個(gè)例子給出的)的細(xì)胞外亞區(qū)域,和果蠅fat腫瘤抑制基因的細(xì)胞外第18個(gè)亞區(qū)域(EC-18,SEQ ID NO99)(fat的細(xì)胞外第18個(gè)亞區(qū)域是一個(gè)原型fat亞區(qū)域)之間的氨基酸同一性確定結(jié)果,例如其中“N-EC-1×pc42”表示N-鈣粘著蛋白的細(xì)胞外第一亞區(qū)域與水平軸上指示的pc42的細(xì)胞外亞區(qū)域可相比。
表1EC-1 EC-2 EC-3 EC-4 FEC-5 E5C-6 EC-7N-EC-1×pc4220272626 3129 17N-EC-1×pc4331232326 3124N-EC-2×pc4228303230 3731 19N-EC-2×pc4330283036 2930N-EC-3×pc4221263029 3130 22N-EC-3×pc4325182628 2825N-EC-4×pc4228282625 2927 17N-EC-4×pc4321252828 2924N-EC-5×pc4224212524 2419 12N-EC-5×pc4315212020 2516fat EC-18×pc42 22353234 4235 19fat EC-18×pc43 32303636 3329pc42和pc43、N-鈣粘著蛋白EC-1至EC-5及果蠅fat EC-18的細(xì)胞外亞區(qū)域之間的氨基酸同一性值基本上小于40%。這些同一性值與其他鈣粘著蛋白亞類的亞區(qū)域之間的同一性值差不多。然而,較高的同一性值表示pc42和pc43與fat比與N-鈣粘著蛋白關(guān)系更為密切。
下列表2中給出人pc42和pc43的細(xì)胞外亞區(qū)域間的氨基酸同一性確定結(jié)果。
表2pc42pc43EC-1 FC-2 EC-3 EC-4 EC-5 EC-6 EC-7EC-133272926252625EC-226382933342821EC-326324130323122EC-425343041393118EC-523322927363416EC-625252625282326各個(gè)EC-1、EC-2、EC-3、EC-4、EC-5亞區(qū)域和pc42和pc43之最后亞區(qū)域間的同一性值一般高于原鈣粘著蛋白與N-鈣粘著蛋白相比較所得到的值。這些結(jié)果提示,pc42和pc43相互間的關(guān)系比它們與典型鈣粘著蛋白的關(guān)系更為密切。
圖1A-C顯示pc42(EC-1至EC-7)、pc43(EC-1至EC-6)、小鼠N-鈣粘著蛋白(EC-1至EC-5)和果蠅fat EC-18的細(xì)胞外亞區(qū)域之排成行的推測(cè)的氨基酸序列。圖1A中一行上的序列延續(xù)到圖1B和1C中同一行上。對(duì)最大同源性部分引入缺口?!盎颉毙兄杏纱髮懽帜该枋龅陌被釟埢且源笥贜-鈣粘著蛋白、pc42、pc43和果蠅fat亞區(qū)域之一半的形式給出的?;蛐兄杏尚懽帜该枋龅陌被釟埢谌藀c42、pc43和果蠅fat中較不保守。圖1A-C顯示,其他鈣粘著蛋白細(xì)胞外區(qū)域重復(fù)的許多氨基酸特征在pc42和pc43序列中是保守的,其中包括鈣粘著蛋白序列基序DXD、DRE和DXNDNXPXF(SEQ ID NO43)、兩個(gè)甘氨酸殘基,和一個(gè)谷氨酸殘基。另外,pc42和pc43與N-鈣粘著蛋白相比,它們共享獨(dú)特的特征。在pc42和pc43之間,特定位點(diǎn)上的更多氨基酸是保守的,如接近pc42和pc43亞區(qū)域之氨基末端的DXDXGXN(SEQ ID NO100)原鈣粘著蛋白序列基序和接近亞區(qū)域之羧基末端的AXDXGXP(SEQ ID NO101)序列基序。再者,兩原鈣粘著蛋白在接近EC-1之羧基末端、EC-2和EC-4的中間,及最后一個(gè)重復(fù)序列的羧基末端共享一個(gè)與典型鈣粘著蛋白基序(N-鈣粘著蛋白的)并不顯著同源的區(qū)域。一個(gè)半胱氨酸殘基位于pc42和pc43之EC-4中部的相似位置上。一般說來,pc42和pc43的細(xì)胞外亞區(qū)域比N-鈣粘著蛋白的細(xì)胞外亞區(qū)域更相似于fat的EC-18。
可能變換的剪接對(duì)各種重疊原鈣粘著蛋白cDNA克隆的序列分析表明,有些克隆在3′末端含有獨(dú)特的序列,但5′末端序列是與其他克隆相同的。形成3′末端區(qū)域之邊界的序列與mRNA剪接的共有序列一致,提示這些克隆可能相應(yīng)于變換剪接的mRNAs。SEQ ID NOs102和103中列出變換剪接pc42mRNA的一個(gè)可能產(chǎn)物的DNA序列和由之推測(cè)的氨基酸序列。SEQ ID NO104和105,以及SEQ ID NOs106和107中分別列出變換剪接pc43mRNA之兩個(gè)可能產(chǎn)物的DNA序列及由之推測(cè)的氨基酸序列。
染色體定位用常規(guī)方法確定原鈣粘著蛋白413基因(SEQ ID NO37)和pc42及pc43基因的染色體定位。
簡(jiǎn)單地說,按以前已描述的方法(Seldin,et al.,J.Exp.Med.,167688-693(1988))喂養(yǎng)C3H/HeJ-gld和Mus spretus(西班牙)小鼠和[(C3H/HeJ-gld×Nus spretus)F1×C3H/HeJ-gld]種間回交小鼠。交配中選擇Mus spretus作為第二親代,因?yàn)榕c使用常規(guī)純系實(shí)驗(yàn)品系進(jìn)行交配相比,相對(duì)更易可確定信息性限制片段長(zhǎng)度變異體(RFLVs)。以分離分析法確定基因連鎖。
用限制性核酸內(nèi)切酶消化以標(biāo)準(zhǔn)技術(shù)從小鼠器官中分離的基因組DNA,并在0.9%瓊脂糖凝膠中電泳分離10μg樣品。將DNA轉(zhuǎn)移到Nytran膜(Schleicher&Schull,Inc.,Keene,NH)上,于65℃與適當(dāng)?shù)奶结橂s交并在嚴(yán)格條件下洗膜(各操作均參見Maniatis等人上述文獻(xiàn))。為了定位pc42基因,可使用相當(dāng)于SEQ ID NO94之核苷酸1419至1906的小鼠序列探針;為了定位pc43基因則使用相當(dāng)于SEQ ID NO96之核苷酸1060至1811的大鼠序列探針。為了定位原鈣粘著蛋白413基因可使用包含SEQ ID NO37中所列序列的探針。目前研究用作探針的其他克隆和用以確定無名DNA座位的RFLV是前已描述過的(染色體7、DNA片段、Washington12(D7Was12);甲狀旁腺激素(Pth);降鈣素(Calc);血紅蛋白,β鏈(Hbb);金屬硫蛋白-I(Mt-1)腺嘌呤磷酸核糖基轉(zhuǎn)移酶(Aprt);生長(zhǎng)激素受體(Ghr);前列腺素E受體EP2亞型(Ptgerep2);二氫葉酸還原酶-2(Dhfr2)成纖維細(xì)胞生長(zhǎng)因子a(Fgfa)和糖皮質(zhì)醇受體-1(Grl-1))。
將原鈣粘著蛋白基因的單元型分布與就整個(gè)小鼠基因組座位所確定的分布相比較,得以分別對(duì)其進(jìn)行圖譜分析以確定它在小鼠染色體上的特定區(qū)域定位。連鎖的可能性大小99%,并表明pc42基因和pc43基因排布為染色體18。原鈣粘著蛋白413基因的排布為染色體7。pc42和pc43基因圖譜限定的染色體18的區(qū)域相當(dāng)于ataxia(ax)座位(Burt,Anat.Rec.,19661-69(1980);Lyon,J,Hered.,4677-80(1955))和twirler(Tw)座位(Lyon,J.Embryol.Exp.Morphol.,6105-116(1958)),而原鈣粘著蛋白413基因圖譜限定的染色體7的區(qū)域相當(dāng)于Shaker(sh-1)座位(Kikuchi et al.,Acta Oto-Laryngol.,60287-303(1965)和Lord et al.,Am.Nat.,63453-442(1929))。這些基因座位已被卷入與之相關(guān)的小鼠遺傳性神經(jīng)疾病中。這一結(jié)果與顯示pc42和pc43在腦中,特別是大腦中被強(qiáng)表達(dá)的原位雜交實(shí)驗(yàn)結(jié)果(見實(shí)施例12)相一致。
實(shí)施例4使用實(shí)施例1中所述的大鼠原鈣粘著蛋白片段作為探針,分離兩種另外的新的人原鈣粘著蛋白cDNA和一種另外的新的大鼠原鈣粘著蛋白cDNA。
首先,使用大鼠克隆RAT-214(SEQ ID NO7)作為探針篩選大鼠腦cDNA文庫(Stratagene,La Jolla,CA)。最后的洗滌步驟是于50℃在0.1×SSC中用0.1%SDS洗兩次,每次15分鐘。鑒定含有編碼相關(guān)原鈣粘著蛋白氨基酸序列之部分cDNA插入段的各種不同的克隆。SEQ ID NO108中列出了一個(gè)定名為#6-2的新的大鼠克隆的核苷酸序列。SEQ ID NO108的前15個(gè)核苷酸是接頭序列而不是大鼠#6-2克隆的一部分。
用克隆#6-2之0.7kbp PstI片段篩選從Stratagene得到的人胎腦cDNA文庫。該片段似乎編碼大鼠原鈣粘著蛋白的EC-2和EC-3。篩選大約2×106個(gè)噬斑后,分離11個(gè)陽性克隆。對(duì)克隆進(jìn)行序列測(cè)定以鑒定稱為人pc3的新的人原鈣粘著蛋白全長(zhǎng)cDNA。SEQID NO109和110中列出了人pc3的核昔酸和推斷的氨基酸序列。
還使用大鼠克隆#6-2的0.7kbp PstI片段重篩選大鼠全長(zhǎng)cDNA克隆的Stratagene大鼠腦cDNA文庫。分離含有編碼新的原鈣粘著蛋白全長(zhǎng)cDNA之插入段的克隆。SEQ ID NO111和NO112中列出了該插入段的DNA和由之推斷的氨基酸序列。因?yàn)榛谛蛄斜容^,全長(zhǎng)大鼠cDNA似乎不是與人pc3克隆同源的,故將其定名為pc5。
同時(shí),使用定名為#43(SEQ ID NO113)的大鼠部分cDNA的0.8kbp EcoRI-PstI片段(該片段是用相當(dāng)于人pc43胞漿區(qū)域的探針篩選Stratagene大鼠腦cDNA文庫而得到的)作為探針探測(cè)Stratagene人cDNA文庫以篩選人原鈣粘著蛋白全長(zhǎng)cDNA。該片段似乎編碼克隆#43的EC-3至EC-6的開始部分。鑒定出的一個(gè)部分克隆編碼稱為人pc4的新的人原鈣粘著蛋白。SEQ ID NO114和115中列出了人pc4克隆的核苷酸序列和由之推斷的氨基酸序列。由pc4克隆編碼的氨基酸序列似乎在pc4之EC-2的中間開始并通過原鈣粘著蛋白的胞漿尾部延續(xù)。
實(shí)施例5使用pRC/RSV表達(dá)載體(Invitrogen,San Diego,California)在L細(xì)胞(ATCC CCLl)中表達(dá)編碼pc42和pc43的全長(zhǎng)人cDNA。經(jīng)用SspI消化然后用DNA聚合酶修成平末端并用XbaI消化(pc42),或者用SpeI和EcoRV雙消化(pc43)以從實(shí)施例2所述的Bluescript SK(+)克隆中分離cDNA。用HindIII消化pRC/RSV表達(dá)載體,然后修成平端并再次用XbaI消化以插入pc42序列,或者用XbaI消化然后修成平端并再用SpeI消化以插入pc43序列。將分離出的原鈣粘著蛋白DNA連接到線性化的pRC/RSV載體中。用CsCl梯度離心法純化所得到的稱為pRC/RSV-pc42的pc42表達(dá)質(zhì)粒(ATCC69162)和稱為pRC/RSV-pc43的pc43表達(dá)質(zhì)粒(ATCC69163),并用磷酸鈣法轉(zhuǎn)染到L細(xì)胞中。
pc42和pc43轉(zhuǎn)染體形態(tài)上相似于親本細(xì)胞。對(duì)經(jīng)pc42或pc43DNA序列轉(zhuǎn)染的L細(xì)胞的Northern印跡分析顯示,被轉(zhuǎn)染的細(xì)胞表達(dá)了有預(yù)期編碼特定原鈣粘著蛋白之大小的mRNA。
實(shí)施例6產(chǎn)生對(duì)pc42和pc43特異的兔多克隆抗體及對(duì)pc43特異的小鼠單克隆抗體。
對(duì)pc42和pc43特異的多克隆抗體的制備將編碼pc42和pc42之細(xì)胞外區(qū)域部分的DNA序列分別與麥芽糖結(jié)合蛋白編碼序列融合并在細(xì)菌中表達(dá)之。具體地說,用PCR方法制備相當(dāng)于之pc42之EC-4至EC-7和pc43之EC-3至EC-5的DNA并以正確讀碼亞克隆到pMAL表達(dá)載體(New England Biolabs.Beverly,Massachusetts)的多克隆位點(diǎn),所說的表達(dá)載體含有編碼直接在該多克隆位點(diǎn)之上游的麥芽糖結(jié)合蛋白質(zhì)的序列。然后用單步驟轉(zhuǎn)化法將所得質(zhì)粒導(dǎo)入E.Coli NM522細(xì)胞(Invitrogen,SanDiego,California)中。并按制造商所述加入IPTG誘導(dǎo)融合蛋白質(zhì)的表達(dá),用直鏈淀粉樹脂親和層析(New England Biolabs)從細(xì)胞提取物中純化融合蛋白質(zhì)。不經(jīng)進(jìn)一步純化即可使用該融合蛋白質(zhì)免疫兔。
用加在弗氏完全佐劑中的500μg純化的融合蛋白質(zhì)在四個(gè)皮下位點(diǎn)免疫兔以制備多克隆抗體。繼后用加在弗氏不完全佐劑中的100μg融合蛋白質(zhì)進(jìn)行免疫。使免疫血清穿過偶聯(lián)到麥芽糖結(jié)合蛋白質(zhì)上的瓊脂糖凝膠(New England Biolabs),并使用由純化的融合蛋白質(zhì)與CNBr Sepharose(Pharmacia)反應(yīng)而制得的Sepharose親和層析柱從免疫血清中純化多克隆抗體。進(jìn)一步證實(shí)了多克隆血清與純化的pc42融合蛋白質(zhì)和pc42轉(zhuǎn)染的細(xì)胞提取物(如實(shí)施例5中所述的)的反應(yīng)性。
對(duì)pc43特異的單克隆抗體的制備按照Kennett(Methods in Enzymol.,58345-359(1978))的方法,使用pc43融合蛋白質(zhì)(含有pc43的EC-3至EC-5亞區(qū)域)在小鼠體內(nèi)產(chǎn)生單克隆抗體。簡(jiǎn)單地說,在兩個(gè)皮下位點(diǎn)用pc43融合蛋白質(zhì)(100μg)免疫小鼠。將得自有最高滴度之小鼠的脾細(xì)胞與NS1骨髓瘤細(xì)胞系融合。以ELISA檢測(cè)法篩選與pc43融合蛋白質(zhì)及與麥芽糖結(jié)合蛋白質(zhì)有反應(yīng)性的所得雜交瘤的上清液。亞克隆與pc43細(xì)胞外區(qū)域有最高反應(yīng)性的融合孔。稱為38I2C的雜交瘤細(xì)胞系(ATCC HB11207)產(chǎn)生對(duì)pc43特異的IgG1亞型單克隆抗體。經(jīng)免疫印跡實(shí)施例5中所述的pc43L細(xì)胞轉(zhuǎn)染體進(jìn)一步證實(shí)由雜交瘤細(xì)胞系38I2C產(chǎn)生的單克隆抗體與pc43的反應(yīng)性。38I2C單克隆抗體是對(duì)人pc43特異的。
實(shí)施例7用免疫印跡法和免疫熒光顯微鏡檢法檢測(cè)用實(shí)施例5中制備的編碼pc42和pc43的DNA序列轉(zhuǎn)染的L細(xì)胞對(duì)原鈣粘著蛋白的表達(dá)。
免疫印跡分析對(duì)pc42和pc43轉(zhuǎn)染體的細(xì)胞提取物進(jìn)行SDS-PAGE分離,然后電轉(zhuǎn)印到PVDF膜(Millipore,Bedford,Massachusetts)上。在Tris緩沖鹽水(TBS)中將該膜與5%脫脂乳一起保溫2小時(shí),然后分別與pc42多克隆血清或pc43單克隆抗體保溫1小時(shí)。用含有0.05%吐溫20的TBS將膜洗3次(各5分鐘),并在同樣緩沖液中分別與結(jié)合有堿性磷酸酶的抗兔IgG抗體或抗小鼠IgG抗體(Promega,Madison,Wisconsin)保溫1小時(shí)。用含有0.05%吐溫20的TBS洗膜后,使用Western Blue溶液(Promega)顯現(xiàn)肉眼可見的反應(yīng)性帶。
抗pc42多克隆抗體著染pc42轉(zhuǎn)染的細(xì)胞中的,而不是親本L細(xì)胞中的分子量約為170kDa的帶。pc43特異性單克隆抗體(38I2C)和多克隆抗體著染pc43轉(zhuǎn)染之細(xì)胞中的兩條分子量約為150kDa的相鄰帶。pc43抗體并不著染親本L細(xì)胞中的帶。經(jīng)用pc42和pc43抗體著染電泳帶,所指示的分子量明顯大于由推斷的氨基酸序列預(yù)測(cè)的分子量。這種分子量的差異在各種鈣粘著蛋白相關(guān)蛋白質(zhì)間是常見的,并且可能歸因于糖基化作用和/或鈣粘著蛋白特異性的結(jié)構(gòu)特性。pc42抗體也著染可能是蛋白水解降解產(chǎn)物的較小帶。
當(dāng)用胰酶處理被轉(zhuǎn)染的細(xì)胞并制備細(xì)胞提取物,在SDS/PAGE上電泳分離并用適當(dāng)?shù)目贵w進(jìn)行免疫印跡分析時(shí),發(fā)現(xiàn)由被轉(zhuǎn)染的細(xì)胞表達(dá)的pc42和pc43多肽對(duì)蛋白水解高度敏感,并且容易通過0.01%胰蛋白酶處理消化。但與典型的鈣粘著蛋白相反,這些蛋白質(zhì)在1-5mM Ca2+存在下不能兔于被消化。
免疫熒光顯微鏡檢使被轉(zhuǎn)染的細(xì)胞生長(zhǎng)在被粘連蛋白預(yù)包被的蓋片上,并于室溫下用4%多聚甲醛固定5分鐘,或者在冰上用冷甲醇處理10分鐘,然后再用4%多聚甲醛固定。用TBS洗滌后,將細(xì)胞與含有1%BSA的TBS保溫30分鐘,再于室溫下在含有1%BSA的TBS中與抗pc42多克隆抗體或抗pc43單克隆抗體保溫1小時(shí)。然后用含有0.01%BSA的TBS洗蓋片并在室溫下分別與結(jié)合有FITC的抗兔抗體或抗小鼠抗體(Cappel,Durham,North Carolina)一起保溫60分鐘。再次用含有0.01%BSA的TBS洗細(xì)胞并進(jìn)行熒光顯微鏡檢。pc42特異性和pc43特異性多克隆抗體都著染表達(dá)原鈣粘著蛋白蛋白質(zhì)之被轉(zhuǎn)染細(xì)胞的細(xì)胞邊緣區(qū),主要是在細(xì)胞-細(xì)胞接觸部位。這些抗體不著染親本L細(xì)胞,兔預(yù)免疫血清均不著染pc42和pc43轉(zhuǎn)染體。
實(shí)施例8檢驗(yàn)被轉(zhuǎn)染的表達(dá)原鈣粘著蛋白蛋白質(zhì)之L細(xì)胞的細(xì)胞聚集特性。在含有10%胎牛血清的Dulbecco氏改動(dòng)的Eagle氏培養(yǎng)基(DMEM)(Gibco,Grand Island,New York)中于37℃和5%CO2環(huán)境下培養(yǎng)被轉(zhuǎn)染的L細(xì)胞。在旋轉(zhuǎn)振蕩器上于37℃用存在有1mMEGTA的0.01%胰蛋白酶將生長(zhǎng)至接近匯合的細(xì)胞處理25分鐘,然后離心收集之。加入大豆胰蛋白酶抑制劑后用無Ca2+的HEPES緩沖鹽水(HBS)將細(xì)胞洗3次,并重新懸浮于含有1%BSA的HBS中。在旋轉(zhuǎn)振蕩器上,于DMEM和含1%BSA、2mM CaCl2及20μg/ml脫氧核糖核酸酶之HBS的1∶1混合物中將重新懸浮的細(xì)胞于37℃保溫30分鐘至6小時(shí),以完成細(xì)胞聚集試驗(yàn)(Urushihara et al.,Dev.Biol.,70206-216(1979))。
在保溫不到1小時(shí)的期間內(nèi),pc42和pc43轉(zhuǎn)染體沒有顯示任何明顯的細(xì)胞聚集活性。這一結(jié)果正好與典型鈣粘著蛋白在相似實(shí)驗(yàn)中所發(fā)生的細(xì)胞聚集相反(Nagafuchi et al.,文獻(xiàn)同上;Hatta etal.,文獻(xiàn)同上)。但延長(zhǎng)被轉(zhuǎn)染細(xì)胞的保溫時(shí)間(超過1-2小時(shí))則可見細(xì)胞逐漸再聚集成小的聚集體。當(dāng)在Ca2+存在下經(jīng)用胰蛋白酶處理制備被轉(zhuǎn)染細(xì)胞的單細(xì)胞懸液時(shí)可得到相似的結(jié)果。當(dāng)試驗(yàn)未被轉(zhuǎn)染的L細(xì)胞或只用pRC/RSV載體轉(zhuǎn)染的L細(xì)胞時(shí),在相同條件下未觀察到再聚集現(xiàn)象。當(dāng)在細(xì)胞聚集試驗(yàn)中將用DiO(MolecularProbes,Eugene,OR)標(biāo)記的pc43轉(zhuǎn)染體與未被標(biāo)記的pc42轉(zhuǎn)染體一起保溫時(shí),標(biāo)記的和未標(biāo)記的細(xì)胞的聚集幾乎是互不相容的,此表明原鈣粘著蛋白結(jié)合是同嗜性的。
鑒于原鈣粘著蛋白胞漿區(qū)域沒有表現(xiàn)出與鈣粘著蛋白區(qū)域有明顯的同源性這一事實(shí),故進(jìn)行相應(yīng)實(shí)驗(yàn)以確定是否胞漿區(qū)域的差異可以說明在鈣粘著蛋白和原鈣粘著蛋白轉(zhuǎn)染體中觀察到的細(xì)胞聚集活性差異的原因。用E-鈣粘著蛋白的胞漿區(qū)域取代pc43的胞漿區(qū)域并分析用嵌合構(gòu)建體轉(zhuǎn)染之細(xì)胞的聚集。
用EcoRV消化實(shí)施例2中所述的含有pc43之完整編碼序列的Bluescript SK(+)克隆,然后再用XbaI部分消化以除去相當(dāng)于胞漿區(qū)域的序列,并經(jīng)瓊脂糖凝膠電泳純化質(zhì)粒DNA。使用從小鼠肺mRNA制得的小鼠cDNA作為模板,并使用相當(dāng)于接近胞漿區(qū)域序列之N末端的區(qū)域或含有小鼠E-鈣粘著蛋白之終止密碼子的區(qū)域作為特異性引物(Nagafuchi et al.,文獻(xiàn)同上),以PCR法合成相當(dāng)于小鼠E-鈣粘著蛋白之胞漿區(qū)域的cDNA。XbaI序列被包括在上游引物的5′末端。然后將E-鈣粘著蛋白胞漿區(qū)域cDNA亞克隆到線性化的pc43Bluescript克隆中。用SpeI和EcoRV切下含有所得完整嵌合序列的DNA并亞克隆到表達(dá)載體pRC/RSV載體的SpeI切平頭的XbaI位點(diǎn)中。最后,以磷酸鈣法用所得構(gòu)建體轉(zhuǎn)染L細(xì)胞。用G418篩選約10天后,用FITC標(biāo)記的38I2C抗pc43抗體著染轉(zhuǎn)化體并進(jìn)行FACS分析。分離一部分高標(biāo)記的細(xì)胞并克隆之。轉(zhuǎn)染體顯示有與親本L細(xì)胞相似的形態(tài),并使用pc43抗體以免疫熒光顯微鏡檢測(cè),在細(xì)胞周邊定位所表達(dá)的蛋白質(zhì)。
按下述方法分析嵌合轉(zhuǎn)染體的細(xì)胞聚集活性。室溫下用DiO將嵌合pc43轉(zhuǎn)染體標(biāo)記20分鐘。在1mM EGTA存在下用胰蛋白酶處理所得到的細(xì)胞并制成單細(xì)胞懸液。然后,將細(xì)胞與未標(biāo)記的其他類型轉(zhuǎn)染體混合并在旋轉(zhuǎn)振蕩器上保溫2小時(shí)。用熒光和相差顯微鏡檢查實(shí)驗(yàn)結(jié)果。在標(biāo)準(zhǔn)檢測(cè)培養(yǎng)基中,于多克隆抗pc43抗體(100ng/ml)存在下保溫轉(zhuǎn)染體以檢查抗體對(duì)細(xì)胞聚集的抑制作用。
在細(xì)胞聚集試驗(yàn)中,在40分鐘保溫時(shí)間內(nèi)嵌合pc43轉(zhuǎn)染體顯示了明顯的Ca2+依賴性細(xì)胞聚集作用。加入pc43特異性多克隆抗體后可抑制細(xì)胞聚集。
實(shí)施例9使用Maruyama等人(J.Biochem.,95511-519(1984))的方法,在加或不加鈣-45條件下經(jīng)Western印跡分析確定pc43的鈣結(jié)合特性。將實(shí)施例6中所述的含有pc43亞區(qū)域EC-3至EC-5的pc43融合蛋白質(zhì)與鈣結(jié)合蛋白質(zhì)鈣調(diào)蛋白相比較。對(duì)純化的pc43融合蛋白質(zhì)的樣品進(jìn)行SDS/PAGE并電泳轉(zhuǎn)移到PVDF膜上。使用放射自顯影響術(shù)檢測(cè)45Ca2+與pc43融合蛋白質(zhì)的結(jié)合,并確定該結(jié)合幾乎與45Ca2+對(duì)鈣調(diào)蛋白的結(jié)合一樣有效。相反,鈣沒有與純化的缺少pc43細(xì)胞外區(qū)域的麥芽糖結(jié)合蛋白質(zhì)結(jié)合。pc43亞區(qū)域EC-3至EC-5含有與見于E-鈣粘著蛋白中的推斷Ca2±結(jié)合基序高度同源的序列(參見(Ringwald et al.,EMBO J.,63647-3653(1987))。
實(shí)施例10用Northern印跡法檢測(cè)各種組織和細(xì)胞系中編碼pc42和pc43之mRNA的表達(dá)。
用異硫氰酸鈲法制備總RNA并使用FastTrack試劑盒(Invitrogen)分離poly(A)+RNAs。在變性條件下用0.8%瓊脂糖凝膠電泳分離RNA制劑并使用毛細(xì)管法將之轉(zhuǎn)移到硝酸纖維素濾膜上。按照Thomas(Proc.Natl.Acad.Sci.USA,775201-5205(1980))的方法進(jìn)行Northern印跡分析。最后于65℃在含有0.1%十二烷基硫酸鈉的0.2×標(biāo)準(zhǔn)檸檬酸鹽鹽水中將濾膜洗10分鐘。
原鈣粘著蛋白mRNA在成年大鼠組織中的表達(dá)在變性條件下電泳分離包括腦、心臟、肝臟、肺、皮膚、腎臟及肌肉在內(nèi)的大鼠組織中的總mRNA制劑(10μg mRNA/泳道),并轉(zhuǎn)移到硝酸纖維素濾膜上。將所得濾膜與32P標(biāo)記的eDNA片段MOUSE-326(其相當(dāng)于人pc42的EC-4)和RAT-218(相當(dāng)于人pc43的EC-5)雜交。兩種原鈣粘著蛋白的mRNA在腦組織中均呈高度表達(dá)。pc42探針檢測(cè)到-條大小為7kb的主帶和一條大小為4kb的付帶,可能代表替換剪接的產(chǎn)物。pc43探針與5kb大小的主帶以及較小的付帶雜交。
原鈣粘著蛋白mRNA在大鼠腦中的發(fā)育表達(dá)為了檢查對(duì)原鈣粘著蛋白之mRNA表達(dá)的發(fā)育調(diào)節(jié)作用,制備胚胎第17和20天、新生第5和11天的大鼠以及成年大鼠的腦mRNA,并對(duì)其進(jìn)行如上所述的用于檢查其他大鼠組織的Northern印跡分析。使用β-肌動(dòng)蛋白作為內(nèi)部標(biāo)準(zhǔn)。當(dāng)與β-肌動(dòng)蛋白表達(dá)比較時(shí),可見在腦的胚胎發(fā)育期間增加了表達(dá)pc42和pc43蛋白質(zhì)的mRNA水平。
人的細(xì)胞系中的原鈣粘著蛋白mRNA表達(dá)使用32P標(biāo)記的用于表達(dá)的pc42和pc43mRNA,以Northern印跡法檢測(cè)幾種神經(jīng)元和膠原細(xì)胞系(包括人SK-N-SH成神經(jīng)細(xì)胞瘤、人U251神經(jīng)膠質(zhì)瘤和小鼠Neuro-2a成神經(jīng)細(xì)胞瘤細(xì)胞系)。用HUMAN-42(相當(dāng)于人pc42的EC-4)和HUMAN-43(相當(dāng)于人pc43的EC-5)cDNA片段探查人細(xì)胞系,同時(shí)用MOUSE-326(相當(dāng)于人pc42的EC-4)和RAT-322(相當(dāng)于人pc43的EC-5)cDNA片段探查小鼠細(xì)胞系。發(fā)現(xiàn)SK-N-SH人成神經(jīng)細(xì)胞瘤細(xì)胞和U251人神經(jīng)膠質(zhì)瘤細(xì)胞表達(dá)pc43mRNA并發(fā)現(xiàn)Neuro-2a小鼠成神經(jīng)細(xì)胞瘤細(xì)胞表達(dá)pc42mRNA。
實(shí)施例11用Western印跡法和免疫熒光顯微鏡檢術(shù)檢測(cè)pc43蛋白質(zhì)在各種組織、提取物及細(xì)胞中的表達(dá)。
在大鼠心肌提取物中的表達(dá)切除后在液氮中冷凍心臟,在研缽中研成粒末、在加于0.5%Nonidet P40(在10mM PIPES(pH6.8)、50mMNaCl、250mM(NH4)2SO4、300mM蔗糖、3mM MgCl2中)內(nèi)的Polytron中簡(jiǎn)單研磨并微量離心15分鐘,以制備大鼠心臟無離子去污劑提取物。經(jīng)SDS/PAGE分離樣品并電泳轉(zhuǎn)移到硝酸纖維素膜上(Towbin et al.,PNAS 764350-4354(1979))。按實(shí)施例7中所述的免疫印跡法,使用兔抗pc43多克隆抗體檢測(cè)出兩條分子量為150kDa和140kDa的pc43蛋白質(zhì)帶。
在組織切片和細(xì)胞中的表達(dá)為了確定原鈣粘著蛋白在各種組織中的定位,切下人和成年大鼠組織,在溶于PBS中的30%蔗糖中4℃保溫30分鐘,在加于冷凍模中的OCT化合物(Tissue-Tek,Elkhart,Indiana)中包埋并快速冷凍。切出6微米切片并放在玻片上。用PBS洗玻片并在3%多聚甲醛中固定5分鐘。為了通透組織切片,將玻片在-20℃丙酮中浸泡10分鐘并風(fēng)干。用溶于PBS中的2%羊血精和1%BSA將切片封閉30分鐘后,室溫下與兔抗pc43多克隆抗血清保溫1小時(shí)。在含0.1%BSA的PBS中將切片淋洗3次并與含1%BSA(溶于PBS)的生物素化的抗兔血清(Vector Laboratories,Burlingame,California)一起保溫30分鐘。洗3次后,加入與FITC(Vetor Laboratories)結(jié)合的鏈霉抗生物素蛋白保留30分鐘,然后再洗3次。為進(jìn)行共定位研究,將適當(dāng)?shù)牡谝豢贵w與結(jié)合有TRITC的第二抗體一起使用。
A.肌肉pc43在大鼠心肌中的免疫定位顯示pc43以重復(fù)方式定位,而這是與pc43同肌節(jié)相關(guān)聯(lián)的情況是一致的。肌節(jié)是骨骼肌和心肌中粘連筋膜(fascia adherens)間的重復(fù)性收縮單位。與細(xì)胞骨架蛋白質(zhì)共定位顯示pc43存在于Z線中肌節(jié)的末端上,其中Z線是與結(jié)蛋白和肌動(dòng)蛋白結(jié)合蛋白質(zhì)粘著斑蛋白,以及α-輔肌動(dòng)蛋白相聯(lián)系的。F-肌動(dòng)蛋白的薄微絲是與Z線間的厚肌球蛋白絲相聯(lián)系的。相反,N-鈣粘著蛋白則定位于肌細(xì)胞肌細(xì)胞接觸部位的粘連筋膜接合處的心肌細(xì)胞末端上。pc43在心肌中的定位提示,pc43可能在收縮器向漿膜固著的肌肉收縮中起作用。
在大鼠骨賂肌中觀察到了pc43的相似定位。超結(jié)構(gòu)研究顯示肌營養(yǎng)不良蛋白(Duchenne肌營養(yǎng)不良癥中缺少的基因產(chǎn)物)是肌膜的一種成分(Porter et al.,J.Cell.Biol.,117997-1005(1992))。肌膜是與pc43所在的M和Z線上的收縮器相連的。
B.腦大鼠和人小腦冷凍切片上抗pc43多克隆抗體及單克隆抗體38I2C的反應(yīng)性分別顯示,pc43表達(dá)的主要部位是在含有許多小神經(jīng)元的Purkinje細(xì)胞和顆粒細(xì)胞層中。
C.胎盤在胎盤發(fā)育的早期階段(妊娠的5-7周)還觀察到單克隆抗體38I2C與人合胞體滋養(yǎng)層的強(qiáng)反應(yīng)性。顯示表達(dá)隨胎盤發(fā)育進(jìn)程而逐步降低一現(xiàn)象表明,pc43可能參予受精卵植入腦盤的過程。
D.成神經(jīng)細(xì)胞瘤和星狀細(xì)胞瘤細(xì)胞使用抗pc43抗體進(jìn)行的pc43在SK-N-SH成神經(jīng)細(xì)胞瘤細(xì)胞和UW28星狀細(xì)胞瘤細(xì)胞中的免疫細(xì)胞化學(xué)定位揭示了pc43的點(diǎn)狀細(xì)胞表面分布,并且在某些細(xì)胞中有一個(gè)在神經(jīng)元足部隆起之延伸頂端處的定位。在UW28星狀細(xì)胞瘤細(xì)胞的細(xì)胞-細(xì)胞接觸部位,pc43組織成一系列的平行線。這些線開始在接觸部位并延伸約5微米。用羅丹明-鬼筆環(huán)肽(Molecular Probes,Eugene,Oregon,按制造前所述方法)鑒定F-肌動(dòng)蛋白微絲顯示細(xì)胞中的微絲似乎終止在pc43線性結(jié)構(gòu)處(線性結(jié)構(gòu)從細(xì)胞接觸部位的細(xì)胞邊緣開始延伸)。
用pc43特異性抗體進(jìn)行的免疫印跡研究顯示,其可識(shí)別人SK-N-SH成神經(jīng)細(xì)胞瘤細(xì)胞和UW28星狀細(xì)胞瘤細(xì)胞中的分子量為140kDa的蛋白質(zhì)。
E.成骨細(xì)胞使用單克隆抗體38I2C進(jìn)行的pc43在兩個(gè)人成骨肉瘤細(xì)胞系(SaOS(ATCC HTB 85)和MG-63(ATCC CRL 1427))中和正常人小梁成骨細(xì)胞培養(yǎng)物(Civitelli et al.,J.Clin.Invest.,911888-1896(1993)中所述的培養(yǎng)系統(tǒng))中的免疫細(xì)胞化學(xué)定位研究顯示,pc43以與見于UW28星狀細(xì)胞瘤細(xì)胞中的相似方式在成骨細(xì)胞中表達(dá)。在細(xì)胞-細(xì)胞接觸部位,pc43被組織成似乎相當(dāng)于肌動(dòng)蛋白張力纖維的一系列平行線。另外,在某些細(xì)胞中,pc43似乎定位在接觸細(xì)胞隆起的頂端。Northern印跡分析為pc43在正常人小梁成骨細(xì)胞中表達(dá)提供了進(jìn)一步的證據(jù)。pc43特異性DNA探針與從正常人小梁成骨細(xì)胞分離之poly-A mRNA樣品中的5kb主帶雜交。
實(shí)施例12在大鼠組織的冰凍切片上使用原鈣粘著蛋白特異性RNA探針進(jìn)行原位雜交實(shí)驗(yàn)。
使用Promega公司(Madison,Wisconsin)介紹的標(biāo)準(zhǔn)方法制備正義和反義35S-核糖探針(riboprobes)。使用MOUSE-326cDNA克隆的約400bp EcoRI-XbaI片段作為pc42特異性探針。該片段編碼pc42之EC-3的中部至EC-4的末端。使用RAT-218cDNA克隆的約700bp SmaI片段作為pc43特異性探針。該片段編碼pc43之EC-3的末端至EC-5的末端。
收獲成年大鼠組織并直接用加在冰凍模中的OCT Compound(Tissue-TeK)包埋,并在95%乙醇/干冰溶中快速冷凍。將冷凍塊保存于-80℃下以備切片。使用恒冷切片機(jī)(Reichert-Jung,Model#2800 Frigocut N,Leica,Inc.,Gilroy,California)切出6微米組織切片。將切出的組織切片保存于-80℃。
所使用的原位方法是Angerer等人(Methods in Enzymology,152649-660,(1987))所述方法改動(dòng)方法。用焦碳酸二乙酯(DEPC,Sigma,St.Louis,Missouri)處理所有溶液以除去RNase污染。首先將組織切片置于4%多聚甲醛中4℃固定20分鐘。為除去多余的多聚甲醛并停止組織固定,在PBS(磷酸鹽緩沖鹽水)中洗玻片,在一系列不同濃度乙醇(70、95、100%)中變性處理并干燥之。為了防止在原位處理期間組織從玻片上脫離,在聚-L-賴氨酸溶液(Sigma)中將組織切片室溫處理10分鐘。為使組織中的所有RNA變性,將切片在70%甲酰胺/2×SSC(0.15M NaCl/0.3M檸檬酸鈉,pH7.0)溶液中70℃放置2分鐘,然后在冷卻的2×SSC中漂洗之,在一系列不同濃度的乙醇中脫水并干燥之。干燥后,將切片置于雜交緩沖液(50%甲酰胺/50mM DTT(二硫蘇糖醇)/0.3MNaCl/20mM Tris,pH8.0/5mM EDTA/1×Denhardt氏溶液(0.02%Ficoll 400型/0.02%聚乙烯吡咯烷酮/0.02%BSA)/10%葡聚糖硫酸酯)中于最終雜交溫度下預(yù)雜交約4小時(shí)。預(yù)雜交后,向各切片上加大約1×106cpm的適當(dāng)核糖探針。一般將切片于45℃雜交過夜(12-16小時(shí))。為確保所看到的雜交是特異的,在某些實(shí)驗(yàn)中通過將雜交溫度升高到50℃以增加雜交的嚴(yán)格性。鑒于45℃和50℃實(shí)驗(yàn)均給出差不多的結(jié)果,故將所使用的標(biāo)準(zhǔn)雜交溫度定為45℃。
為了除去過多的未雜交的探針,對(duì)切片進(jìn)行一系列洗滌。首先在4×SSC中淋洗切片以除去大部分雜交溶液和探針。然后于室溫下在4×SSC/50mMDTT中洗15分鐘。還在逐步增加的嚴(yán)格條件下進(jìn)行洗滌。于60℃在50%甲酰胺/2×SSC/50mM DTT中洗40分鐘。最后在室溫下洗滌4次,每次10分鐘兩次在2×SSC中,兩次在0.1×SSC中。在一系列漸增濃度的乙醇中使洗過的切片脫水并干燥之。
為了看到雜交的探針,將玻片浸于已在dH2O中1∶1稀釋的Kodak NTB2核乳液(International Biotechnology,New Haven,Connecticut)中。干燥后,4℃下將玻片在不透光盒中儲(chǔ)存適當(dāng)?shù)钠毓鈺r(shí)間。由兩個(gè)人單獨(dú)觀察原位玻片并記錄陽性或陰性雜交信號(hào)。
所有原位雜交研究均在大鼠組織上進(jìn)行。因?yàn)镹orthern印跡實(shí)驗(yàn)(參見實(shí)施例9)的結(jié)果表明pc42和pc43均在成年腦組織中表達(dá),所以進(jìn)行原位雜交研究以將這些分子的表達(dá)定位于特定類型的腦細(xì)胞上。在正常成年大鼠腦中看到的雜交是特異的(沒有看到與正文探針的本底雜交),并定位于腦的特定區(qū)域。所看到的pc42和pc43表達(dá)的總體特征是很相似的,其主要差異在于表達(dá)水平的不同。pc43的表達(dá)水平似乎低于pc42。兩種分子均在海馬的生發(fā)細(xì)胞和錐體細(xì)胞中、小腦及灰質(zhì)的神經(jīng)元的Purkinje細(xì)胞中表達(dá)。另外,pc42在白質(zhì)的膠質(zhì)細(xì)胞中表達(dá),但與pc43在膠質(zhì)瘤細(xì)胞系中的表達(dá)(如實(shí)施例9中所述)相反,沒有觀察到pc42在正常膠質(zhì)細(xì)胞中的表達(dá)。在脊髓中,兩種原鈣粘著蛋白在灰質(zhì)的運(yùn)動(dòng)神經(jīng)元中表達(dá),并且pc42還在白質(zhì)的膠質(zhì)細(xì)胞中表達(dá)。
當(dāng)分析兩種原鈣粘著蛋白分子在具有EAE(實(shí)驗(yàn)性應(yīng)變性腦脊髓炎)(Vandenbark et al.,Cell.Immunol.,1285-93(1974))之大鼠的腦和脊髓中的表達(dá)時(shí),發(fā)現(xiàn)如上所述的同樣結(jié)構(gòu)是陽性的。另外,觀察到pc42在EAE組織的白細(xì)胞浸潤液中的表達(dá)。經(jīng)兩個(gè)白細(xì)胞細(xì)胞系RBL-1/和y3的原位雜交分析進(jìn)一步證實(shí)pc42在白細(xì)胞中的表達(dá)。
在所試驗(yàn)的所有胚胎學(xué)發(fā)育日(E15-E19)均觀察到原鈣粘著蛋白-42和-43在大鼠胚胎的發(fā)育階段腦組織中的表達(dá)。另外,還在所試驗(yàn)的所有胚胎學(xué)發(fā)育日(E13-E19)觀察到原鈣粘著蛋白-43在發(fā)育階段大鼠心臟中的表達(dá)。這一發(fā)現(xiàn)是與顯示原鈣粘著蛋白-43在成年心臟中表達(dá)的免疫組織化學(xué)分析結(jié)果一致的。
為了確定原鈣粘著蛋白在神經(jīng)系統(tǒng)發(fā)育中的可能作用,還用原位雜交方法檢查原鈣粘著蛋白成員在發(fā)育階段的大鼠腦和成年大鼠腦中的表達(dá)分布圖。將處于出生后第0、6、14、30天(P0至P30)和3個(gè)月(年青成年期)之大鼠腦的一系列冠狀、矢狀和水平斷面切片與相當(dāng)于本發(fā)明的包括pc42、pc43、RAT-212、RAT-411及RAT-418在內(nèi)的各種原鈣粘著蛋白的經(jīng)標(biāo)記cDNA探針雜交。在發(fā)育的腦中,RAT-411在嗅球的神經(jīng)元即僧謂細(xì)胞和球旁細(xì)胞中以高水平表達(dá)。RAT-411mRNA的表達(dá)是瞬時(shí)的;表達(dá)出現(xiàn)在P0、P6達(dá)到降值,至P14減少,在P30時(shí)峰和成年大鼠腦中測(cè)不到表達(dá)。在成年大鼠中,發(fā)現(xiàn)pc43mRNA主要是在小腦的Purkinje細(xì)胞中表達(dá)。從大約在P6時(shí)Purkinje細(xì)胞分化之初即觀察到pc43mRNA在Purkinje細(xì)胞中的表達(dá)。其他原鈣粘著蛋白成員以很低的水平在發(fā)育中的和成年的大鼠腦的各個(gè)部位表達(dá)。這些結(jié)果表明在中樞神經(jīng)系統(tǒng)發(fā)育期間原鈣粘著蛋白成員被得以不同地表達(dá),并且提示RAT-411和pc43在嗅球神經(jīng)元和Purkinje細(xì)胞的發(fā)育期間分別具有特定的作用。
實(shí)施例13使用pc43特異性多克隆抗體和單克隆抗體38I2C進(jìn)行常規(guī)免疫沉淀,以鑒定與L細(xì)胞轉(zhuǎn)化體中pc43相互反應(yīng)的蛋白質(zhì)。
經(jīng)在含有[35S]甲硫氨酸(50μCi/ml)的Dulbecco氏改動(dòng)的Eagle氏培養(yǎng)基中保溫細(xì)胞過夜,代謝上標(biāo)記pc43和嵌合pc43轉(zhuǎn)染體。洗滌后,用含有Triton X-100的PBS裂解轉(zhuǎn)染體細(xì)胞并與抗pc43抗體一起保溫。然后使用蛋白A-Sepharose小珠收集免疫復(fù)合物。室溫下用洗滌緩沖液(50mM Tris-HCl、pH8.0,含有0.5M NaCl,0.1%卵白蛋白、0.5%NP-40、0.5%Triton X-100和1mM EDTA)將得到小珠洗5次。經(jīng)SDS-PAGE分離蛋白質(zhì)并進(jìn)行放射自顯影。
因?yàn)榭功?連環(huán)蛋白和抗β-連環(huán)蛋白抗體著染差不多大小的帶,所以嵌合pc43與很可能相當(dāng)于α-和β-連環(huán)蛋白的105kDa及95kDa帶共沉淀。另一方面,pc43與120kDa帶共沉淀。
雖然已通過特定方法和組成描述了本發(fā)明,但應(yīng)明確的是本領(lǐng)域技術(shù)人員可以對(duì)其進(jìn)行各種改動(dòng)和修飾。因此,僅該對(duì)本發(fā)明作出如出現(xiàn)于權(quán)利要求中的這些限制。
序列表(1)一般資料(i)申請(qǐng)人Suzuki,Shintaro(ii)發(fā)明名稱Protocadherin Materials and Methods(iii)序列數(shù)目115(iv)通訊地址(A)地址Marshall,O′Toole,Gerstein,Murray,&Borun(B)街道6300 Sears Tower,233 S.Wacker Drive(C)城市Chicago(D)州 Illinois(E)國家USA(F)郵政編碼60606(v)計(jì)算機(jī)可讀形式(A)介質(zhì)類型Floppy disk(B)計(jì)算機(jī)IBM PC compatible(C)操作系統(tǒng)PC-DOS/MS-DOS(D)軟件PatentIn Release #1.0,Version#1.25(vi)目前申請(qǐng)信息(A)申請(qǐng)?zhí)?B)提交日(C)分類(vii)在先申請(qǐng)信息(A)申請(qǐng)?zhí)朠CT/US93/12588(B)申請(qǐng)日23 DEC 1993(vii)在先申請(qǐng)信息(A)申請(qǐng)?zhí)朥S07/998,003(B)申請(qǐng)日29 DEC 1992(viii)律師/代理人信息(A)姓名Noland,Greta E.
(B)登記號(hào)35,302(C)參考/文件號(hào)32149(ix)電訊信息(A)電話312/474-6300(B)傳真312/474-0448(C)電傳25-3856(2)SEQ ID NO1的信息(i)序列特征(A)長(zhǎng)度17堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型DNA(xi)序列描述SEQ ID NO1AARSSNNTNG AYTRYGA 17(2)SEQ ID NO2的信息(i)序列特征(A)長(zhǎng)度17堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(i i)分子類型DNA(xi)序列描述SEQ ID NO2TTRCTRTTRC GNGGNNN 17(2)SEQ ID NO3的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)
(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO3AAGGGAGTGG ACTTTGAGGA GCAGCCTGAG CTTAGTCTCA TCCTCACGGC TTTGGATGGA 60GGGACTCCAT CCAGGTCTGG GACTGCATTG GTTCAAGTGG AAGTCATAGA TGCCAATGAC120AACGCACCGT A 131(2)SEQ ID NO4的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO4Lys Gly Val Asp Phe Glu Glu Gln Pro Glu Leu Ser Leu Ile Leu Thr1 5 10 15Ala Leu Asp Gly Gly Thr Pro Ser Arg Ser Gly Thr Ala Leu Val Gln20 25 30Val Glu Val Ile Asp Ala Asn Asp Asn Ala Pro35 40(2)SEQ ID NO5的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股
(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO5AAACGCATGG ATTTCGAGGA GTCTTCCTCC TACCAGATCT ATGTGCAAGC TACTGACCGG 60GGACCAGTAC CCATGGCGGG TCATTGCAAG GTGTTGGTGG ACATTATAGA TGTGAACGAC120AACGCACCTA A 131(2)SEQ ID NO6的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO6Lys Ala Met Asp Phe Glu Glu Ser Ser Ser Tyr Gln Ile Tyr Val Gln1 5 10 15Ala Thr Asp Arg Gly Pro Val Pro Met Ala Gly His Cys Lys Val Leu20 25 30Val Asp Ile Ile Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO7的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA
(xi)序列描述SEQ ID NO7AAGCGACTGG ACTTTGAGAC CCTGCAGACC TTCGAGTTCA GCGTGGGTGC CACAGACCAT 60GGCTCCCCCT CGCTCCGCAG TCAGGCTCTG GTGCGCGTGG TGGTGCTGGA CCACAATGAC120AATGCCCCCA A 131(2)SEQ ID NO8的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO8Lys Arg Leu Asp Phe Glu Thr Leu Gln Thr Phe Glu Phe Ser Val Gly1 5 10 15Ala Thr Asp His Gly Ser Pro Ser Leu Arg Ser Gln Ala Leu Val Arg20 25 30Val Val Val Leu Asp His Asn Asp Asn Ala Pro35 40(2)SEQ ID NO9的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO9AAGGGCCTGG ATTACGAGGC ACTGCAGTCC TTCGAGTTCT ACGTGGGCGC TACAGATGGA 60GGCTCACCCG CGCTCAGCAG CCAGACTCTG GTGCGGATGG TGGTGCTGGA TGACAACGAC120AACGCCCCTA A 131(2)SEQ ID NO10的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO10Lys Gly Leu Asp Tyr Glu Ala Leu Gln Ser Phe Glu Phe Tyr Val Gly1 5 10 15Ala Thr Asp Gly Gly Ser Pro Ala Leu Ser Ser Gln Thr Leu Val Arg20 25 30Met Val Val Leu Asp Asp Asn Asp Asn Ala Pro35 40(2)SEQ ID NO11的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO11AAGGCGTTTG ATTTTGAGGA TCAGAGAGAG TTCCAGCTAA CCGCTCATAT AAACGACGGA 60GGTACCCCGG TTTTGGCCAC CAACATCAGC GTGAACATAT TTGTTACTGA CCGCAATGAC120AACGCCCCGC A 131(2)SEQ ID NO12的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO12Lys Ala Phe Asp Phe Glu Asp Gln Arg Glu Phe Gln Leu Thr Ala His1 5 10 15Ile Asn Asp Gly Gly Thr Pro Val Leu Ala Thr Asn Ile Ser Val Asn20 25 30Ile Phe Val Thr Asp Arg Asn Asp Asn Ala Pro35 40(2)SEQ ID NO13的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO13AAGGCGGTGG ATTACGAAAT CACCAAGTCC TATGAGATAG ATGTTCAAGC CCAAGATCTG 60GGTCCCAATT CTATTCCTGC TCATTGCAAA ATTATAATTA AGGTCGTGGA TGTCAACGAC120AACGCTCCCA A 131(2)SEQ ID NO14的信息(i)序列特征
(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO14Lys Ala Val Asp Tyr Glu Ile Thr Lys Ser Tyr Glu Ile Asp Val Gln1 5 10 15Ala Gln Asp Leu Gly Pro Asn Ser Ile Pro Ala His Cys Lys Ile Ile20 25 30Ile Lys Val Val Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO15的信息(i)序列特征(A)長(zhǎng)度135堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO15TATGACCATG ATTACGAGAC AACCAAAGAA TATACACTGC GGATCCGGGC CCAGGATGGT 60GGCCGGACTC CACTTTCCAA CGTCTCCGGT CTAGTAACCG TGCAGGTCCT AGACATCAAC120GACAATGCCC CCCCA 135(2)SEQ ID NO16的信息(i)序列特征(A)長(zhǎng)度44氨基酸(B)類型氨基酸
(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO16Tyr Asp His Asp Tyr Glu Thr Thr Lys Glu Tyr Thr Leu Arg Ile Arg1 5 10 15Ala Gln Asp Gly Gly Arg Thr Pro Leu Ser Asn Val Ser Gly Leu Val20 25 30Thr Val Gln Val Leu Asp Ile Asn Asp Asn Ala Pro35 40(2)SEQ ID NO17的信息(i)序列特征(A)長(zhǎng)度129堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO17GGGGGGTCGA TTACGAGGAG AACGGCATGT TAGAGATCGA CGTGCAGGCC AGAGACCTAG 60GACCTAACCC AATTCCAGCC CATTGCAAGG TCACAGTCAA GCTCATCGAC CGCAATGATA120ACGCCCCCA129(2)SEQ ID NO18的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO18Arg Gly Val Asp Tyr Glu Glu Asn Gly Met Leu Glu Ile Asp Val Gln1 5 10 15Ala Arg Asp Leu Gly Pro Asn Pro Ile Pro Ala His Cys Lys Val Thr20 25 30Val Lys Leu Ile Asp Arg Asn Asp Asn Ala Pro35 40(2)SEQ ID NO19的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO19AAGGGGTTGG ACTACGAAGA CACCAAACTC CATGAGATTT ACATCCAGGC CAAAGACAAA 60GGTGCCAATC CGGAAGGAGC GCATTGCAAA GTACTGGTAG AGGTTGTGGA CGTTAACGAC120AATGCCCCTC A 131(2)SEQ ID NO20的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO20Lys Gly Leu Asp Tyr Glu Asp Thr Lys Leu His Glu Ile Tyr Ile Gln1 5 10 15Ala Lys Asp Lys Gly Ala Asn Pro Glu Gly Ala His Cys Lye Val Leu20 25 30Val Glu Val Val Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO21的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO21AAGGGTTTGG ACTTTGAGCA AGTAGATGTC TACAAAATCC GCGTTGACGC GACGGACAAA 60GGACACCCTC CGATGGCAGG CCATTGCACT GTTTTAGTGA GGGTATTGGA TGAAAACGAC120AATGCGCCTC T 131(2)SEQ ID NO22的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO22Lys Gly Leu Asp Phe Glu Gln Val Asp Val Tyr Lys Ile Arg Val Asp1 5 10 15
Ala Tnr Asp Lys Gly His Pro Pro Met Ala Gly His Cys Tnr Val Leu20 25 30Val Arg Val Leu Asp Glu Asn Asp Asn Ala Pro35 40(2)SEQ ID NO23的信息(i)序列特征(A)長(zhǎng)度134堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO23AAGGGTATAG ACTTCGAGCA GATCAAGGAC TTCAGCTTTC AAGTGGAAGC CCGGGACGCC 60GGCAGTCCCC AGGCGCTGTC CGGCAACTGC ACTGTCAACA TCTTGATAGT GGATCAGAAC120GACAACGCCC CTAA 134(2)SEQ ID NO24的信息(i)序列特征(A)長(zhǎng)度44氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO24Lys Gly Ile Asp Phe Glu Gln Ile Lys Asp Phe Ser Phe Gln Val Glu1 5 10 15Ala Arg Asp Ala Gly Ser Pro Gln Ala Leu Ala Gly Asn Thr Thr Val20 25 30Asn Ile Leu Ile Val Asp Gln Asn Asp Asn Ala Pro35 40(2)SEQ ID NO25的信息(i)序列特征(A)長(zhǎng)度134堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO25AAGCCGTTCG ACTATGAGCA AACCGCCAAC ACGCTGGCAC AGATTGACGC CGTGCTGGAA 60AAACAGGGCA GCAATAAATC GAGCATTCTG GATGCCACCA TTTTCCTGGC CGATAAAAAC120GACAATGCGC CAGA 134(2)SEQ ID NO26的信息(i)序列特征(A)長(zhǎng)度44氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO26Lys Pro Phe Asp Tyr Glu Gln Thr Ala Asn Thr Leu Ala Gln Ile Asp1 5 10 15Ala Val Leu Glu Lys Gln Gly Ser Asn Lys Ser Ser Ile Leu Asp Ala20 25 30Thr Ile Phe Leu Ala Asp Lys Asn Asp Asn Ala Pro35 40(2)SEQ ID NO27的信息(i)序列特征
(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO27AAGCGGCTGG ATTTCGAACA GTTCCAGCAG CACAAGCTGC TCGTAAGGGC TGTTGATGGA 60GGAATGCCGC CACTGAGCAG CGATGTGGTC GTCACTGTGG ATGTCACCGA CCTCAACGAT120AACGCGCCCT A 131(2)SEQ ID NO28的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO28Lys Arg Leu Asp Phe Glu Gln Phe Gln Gln His Lys Leu Leu Val Arg1 5 10 15Ala Val Asp Gly Gly Met Pro Pro Leu Ser Ser Asp Val Val Val Thr20 25 30Val Asp Val Thr Asp Leu Asn Asp Asn Ala Pro35 40(2)SEQ ID NO29的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸
(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO29AAGGGGATAG ACTTTGAGAG TGAGAATTAC TATGAATTTG ATGTGCGGGC TCGCGATGGG 60GGTTCTCCAG CCATGGAGCA ACATTGCAGC CTTCGAGTGG ATCTGCTGGA CGTAAATGAC120AACGCCCCAC T 131(2)SEQ ID NO30的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO30Lys Gly Ile Asp Phe Glu Ser Glu Asn Tyr Tyr Glu Phe Asp Val Arg1 5 10 15Ala Arg Asp Gly Gly Ser Pro Ala Met Glu Gln His Cys Ser Leu Arg20 25 30Val Asp Leu Leu Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO31的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型cDNA(xi)序列描述SEQ ID NO31AAGGCATTGG ACTTTGAGGC CCGGCGACTG TATTCGCTGA CAGTTCAGGC CACGGACCGA 60GGCGTGCCCT CGCTCACCGG GCGTGCCGAA GCGCTTATCC AGCTGCTAGA TGTCAACGAC120AACGCACCCA T 131(2)SEQ ID NO32的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO32Lys Ala Leu Asp Phe Glu Ala Arg Arg Leu Tyr Ser Leu Thr Val Gln1 5 10 15Ala Thr Asp Arg Gly Val Pro Ler Leu Thr Gly Arg Ala Glu Ala Leu20 25 30Ile Gln Leu Leu Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO33的信息(i)序列特征(A)長(zhǎng)度125堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO33AAGCCAATTG ATTACGAGGC AACTCCATAC TATAACATGG AAATTGTAGC CACAGACAGC 60GGAGGTCTTT CGGGAAAATG CACTGTGTCT ATACAGGTGG TGGATGTGAA CGACAACGCC120CCCAA125(2)SEQ ID NO34的信息(i)序列特征(A)長(zhǎng)度41氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO34Lys Pro Ile Asp Tyr Glu Ala Thr Pro Tyr Tyr Asn Met Glu Ile Val1 5 10 15Ala Thr Asp Ser Gly Gly Leu Ser Gly Lys Cys Thr Val Ser Ile Gln20 25 30Val Val Asp Val Ash Asp Asn Ala Pro35 40(2)SEQ ID NO35的信息(i)序列特征(A)長(zhǎng)度446堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO35AAGCGGGTAG ACTTCGAAAT GTGCAAAAGA TTTTACCTTG TGGTGGAAGC TAAAGACGGA 60GGCACCCCAG CCCTCAGCAC GGCAGCCACT GTCAGCATCG ACCTCACAGA TGTGAATGAT120AACCCTCCTC GGTTCAGCCA AGATGTCTAC AGTGCTGTCA TCAGTGAGGA TGCCTTAGAG 180GGGGACTCTG TCATTCTGCT GATAGCAGAA GATGTGGATA GCAAGCCTAA TGGACAGATT 240CGGTTTTCCA TCGTGGGTGG AGATAGGGAC AATGAATTTG CTGTCGATCC AATCTTGGGA 300CTTGTGAAAG TTAAGAAGAA ACTGGACCGG GAGCGGGTGT CAGGATACTC CCTGCTCATC 360CAGGCAGTAG ATAGTGGCAT TCCTGCAATG TCCTCAACGA CAACTGTCAA CATTGATATT 420TCTGATGTGA ACGACAACGC CCCCCT446(2)SEQ ID NO36的信息(i)序列特征(A)長(zhǎng)度148氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO36Lys Arg Val Asp Phe Glu Met Cys Lys Arg Phe Tyr Leu Val Val Glu1 5 10 15Ala Lys Asp Gly Gly Thr Pro Ala Leu Ser Thr Ala Ala Thr Val Ser20 25 30Ile Asp Leu Thr Asp Val Asn Asp Asn Pro Pro Arg Phe Ser Gln Asp35 40 45Val Tyr Asp Ala Val Ile Ser Glu Asp Ala Leu Glu Gly Asp Ser Val50 55 60Ile Leu Leu Ile Ala Glu Asp Val Asp Ser Lye Pro Aan Gly Gln Ile65 70 75 80Arg Phe Ser Ile Val Gly Gly Asp Arg Asp Asn Glu Phe Ala Val Asp85 90 95Pro Ile Leu Gly Leu Val Lys Val Lys Lys Lys Leu Asp Arg Glu Arg100 105 110Val Ser Gly Tyr Ser Leu Leu Ile Gln Ala Val Asp Ser Gly Ile Pro115 120 125Ala Met Ser Ser Thr Thr Thr Val Asn Ile Asp Ile Ser Asp Val Asn130 135 140Asp Asn Ala Pro145(2)SEQ ID NO37的信息(i)序列特征(A)長(zhǎng)度440堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO37AAGGGGGTTG ATTATGAGAC AAACCCACGG CTACGACTGG TGCTACAGGC AGAGAGTGGA60GGAGCCTTTG CTTTCTCGGT GCTGACCCTG ACCCTTCAAG ATGCCAATGA CAATGCTCCC 120CGTTTCCTGC AGCCTCACTA CGTGGCTTTC CTGCCAGAGT CCCGACCCTT GGAAGGGCCC 180CTGCTGCAGG TGGAAGCAGA CGACCTGGAT CAAGGCTCTG GAGGACAGAT CTCCTACAGT 240CTGGCTGCAT CCCAGCCAGC ACGGGGCTTG TTCCATGTAG ACCCAGCCAC AGGCACTATC 300ACTACCACAG CCATCCTGGA CCGGGAAATC TGGGCTGAAA CACGGCTGGT ACTGATGGCC 360ACAGACAGAG GAAGCCCAGC ATTGGTGGGC TCAGCTACCC TGACAGTGAT GGTCATCGAT 420ACCAACGACA ATGCTCCCCT 440(2)SEQ ID NO38的信息(i)序列特征(A)長(zhǎng)度146氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO38Lys Gly Val Asp Tyr Glu Thr Asn pro Arg Leu Arg Leu Val Leu Gln1 5 10 15
Ala Glu Ser Gly Gly Ala Phe Ala Phe Ser Val Leu Thr Leu Thr Leu20 25 30Gln Asp Ala Asn Asp Asn Ala Pro Arg Phe Leu Gln Pro His Tyr Val35 40 45Ala Phe Leu Pro Glu Ser Arg Pro Leu Glu Gly Pro Leu Leu Gln Val50 55 60Glu Ala Asn Asp Leu Asp Gln Gly Ser Gly Gly Gln Ile Ser Tyr Ser65 70 75 80Leu Ala Ala Ser Gln Pro Ala Arg Gly Leu Phe His Val Asp Pro Ala85 90 95Thr Gly Thr Ile Thr Thr Thr Ala Ile Leu Asp Arg Glu Ile Trp Ala100 105 110Glu Thr Arg Leu Val Leu Met Ala Thr Asp Arg Gly Ser Pro Ala Leu115 120 125Val Gly Ser Ala Thr Leu Thr Val Met Val Ile Asp Thr Asn Asp Asn130 135 140Ala Pro145(2)SEQ ID NO39的信息(i)序列特征(A)長(zhǎng)度124堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO39AAGGTCTCGA TTATGAGGCA ACTCCATATT ATAACGTGGA AATTGTAGCC ACAGATGGTG 60GGGGCCTTTC AGGAAAATGC ACTGTGGCTA TAGAAGTGGT GGATGTGAAC GACGGCGCTC120CAAT 124(2)SEQ ID NO40的信息(i)序列特征(A)長(zhǎng)度41氨基酸
(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO40Lys Gly Leu Asp Tyr Glu Ala Thr Pro Tyr Tyr Asn Val Glu Ile Val1 5 10 15Ala Thr Asp Gly Gly Ala Phe Asp Glu Asn Cys Thr Val Ala Ile Glu20 25 30Val Val Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO41的信息(i)序列特征(A)長(zhǎng)度8氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型DNA(xi)序列描述SEQ ID NO41Asp Xaa Asn Glu Xaa Pro Xaa Phe1 5(2)SEQ ID NO42的信息(i)序列特征(A)長(zhǎng)度8氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型DNA(xi)序列描述SEQ ID NO42Asp Xaa Asp Glu Xaa Pro Xaa phe1 5(2)SEQ ID NO43的信息(i)序列特征(A)長(zhǎng)度9氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型DNA(xi)序列描述SEQ ID NO43Asp Xaa Asn Asp Asn Xaa Pro Xaa Phe1 5(2)SEQ ID NO44的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO44AAGCGGATGG ATTTTGAAGA CACCAAACTC CATGAGATTT ACATCCAGGC CAAAGACAAA 60GGTGCCAATC CCGAAGGAGC GCATTGCAAA GTACTTGTAG AGGTTGTAGA CGTAAACGAC120AACGCCCCAG T 131(2)SEQ ID NO45的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO45Leu Arg Met Asp Phe Glu Asp Thr Lys Leu His Glu Ile Tyr Ile Gln1 5 10 15Ala Lys Asp Lys Gly Ala Asn Pro Glu Gly Ala His Cys Lys Val Leu20 25 30Val Glu Val Val Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO46的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO46AAGGCTTTGG ATTACGAGGA TCAGAGAGAG TTCCAACTAA CAGCTCATAT AAACGACGGA 60GGTACCCCAG TCTTAGCCAC CAACATCAGC GTGAACGTAT TTGTTACTGA CCGCAATGAT120AACGCCCCCT A 131(2)SEQ ID NO47的信息(i)序列特征
(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO47Lys Ala Leu Asp Tyr Glu Asp Gln Arg Glu Phe Gln Leu Thr Ala His1 5 10 15Ile Asn Asp Gly Gly Thr Pro Val Leu Ala Thr Asn Ile Ser Val Asn20 25 30Val Phe Val Thr Asp Arg Asn Asp Asn Ala Pro35 40(2)SEQ ID NO48的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO48AAGCGCTTGG ACTACGAGGA GAGTAACAAT TATGAAATTC ACGTGGATGC TACAGATAAA 60GGATACCCAC CTATGGTTGC TCACTGCACC GTACTCGTGG GAATCTTGGA TGAAAATGAC120AACGCACCCA T 131(2)SEQ ID NO49的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸
(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO49Lys Arg Leu Asp Tyr Glu Glu Ser Asn Asn Tyr Glu Ile His Val Asp1 5 10 15Ala Thr Asp Lys Gly Tyr Pro Pro Met Val Ala His Cys Thr Val Leu20 25 30Val Gly Ile Leu Asp Glu Asn Asp Asn Ala Pro35 40(2)SEQ ID NO50的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO50AAACCGGTGG ACTACGAGAA AGTCAAAGAC TATACCATCG AGATCGTGGC TGTGGATTCC 60GGCAACCCTC CACTCTCTAG CACCAACTCC CTCAAGGTGC AGGTGGTAGA CGTCAACGAT120AACGCCCCTC T 131(2)SEQ ID NO51的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO51Lys Pro Val Asp Tyr Glu Lys Val Lys Asp Tyr Thr Ile Glu Ile Val1 5 10 15Ala Val Asp Ser Gly Asn Pro Pro Leu Ser Ser Thr Asn Ser Leu Lys20 25 30Val Gln Val Val Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO52的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO52AAGCCTTTTG ATTTCGAGGA CACCAAACTC CATGAGATTT ACATCCAGGC CAAAGACAAG 60GGCGCCAATC CCGAAGGAGC ACATTGCAAA GTGTTGGTGG AGGTTGTGGA TGTGAACGAC120AATGCCCCTC A 131(2)SEQ ID NO53的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO53Lys Pro Phe Asp Phe Glu Asp Thr Lys Leu His Glu Ile Tyr Ile Gln1 5 10 15Ala Lys Asp Lys Gly Ala Asn Pro Glu Gly Ala His Cys Lys Val Leu20 25 30Val Glu Val Val Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO54的信息(i)序列特征(A)長(zhǎng)度122堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO54AAAGGTGTCG ATTACGAGGT GAGTCCACGG CTGCGACTGG TGCTGCAGGC AGAGAGTCGA 60GGAGCCTTTG CCTTCACTGT GCTGACCCTG ACCCTGCAAG ATGCCAACGA CAACGCCCCG120AG 122(2)SEQ ID NO55的信息(i)序列特征(A)長(zhǎng)度40氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO55Lys Gly Val Asp Tyr Glu Val Ser Pro Arg Leu Arg Leu Val Leu Gln1 5 10 15
Ala Glu Ser Arg Gly Ala Phe Ala Phe Thr Val Leu Thr Leu Thr Leu20 25 30Gln Asp Ala Asn Asp Asn Ala Pro35 40(2)SEQ ID NO56的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO56AAAGGGATTG ATTACGAGCA GTTGAGAGAC CTACAGCTGT GGGTGACAGC CAGCGACAGC 60GGGGACCCGC CTCTTAGCAG CAACGTGTCA CTGAGCCTGT TTGTGCTGGA CCAGAACGAC120AACGCCCCCC T 131(2)SEQ ID NO57的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO57Lys Gly Ile Asp Tyr Glu Gln Leu Arg Asp Leu Gln Leu Trp Val Thr1 5 10 15Ala Ser Asp Ser Gly Asp Pro Pro Leu Ser Ser Asn Val Ser Leu Ser20 25 30Leu Phe Val Leu Asp Gln Asn Asp Asn Ala Pro35 40(2)SEQ ID NO58的信息(i)序列特征(A)長(zhǎng)度125堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO58AAGGCGGTCG ATTTTGAGCG CACATCCTCT TATCAACTCA TCATTCAGGC CACCAATATG 60GCAGGAATGG CTTCCAATGC TACAGTCAAT ATTCAGATTG TTGATGAAAA CGACAACGCC120CCCCA125(2)SEQ ID NO59的信息(i)序列特征(A)長(zhǎng)度41氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO59Lys Ala Val Asp Phe Glu Arg Thr Ser Ser Tyr Gln Leu Ile Ile Gln1 5 10 15Ala Thr Asn Met Ala Gly Met Ala Ser Asn Ala Thr Val Asn Ile Gln20 25 30Ile Val Asp Glu Asn Asp Asn Ala Pro35 40(2)SEQ ID NO60的信息(i)序列特征
(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO60AAACGGCTAG ACTTTGAAAA GATACAAAAA TATGTTGTAT GGATAGACGC CAGAGATGGT 60GGTTTCCCTC CTTTCTCCTC TTACGAGAAA CTTGATATAA CAGTATTAGA TGTCAACGAT120AACGCGCCTA A 131(2)SEQ ID NO61的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO61Lys Arg Leu Asp Phe Glu Lys Ile Gln Lys Tyr Val Val Trp Ile Glu1 5 10 15Ala Arg Asp Gly Gly Phe Pro Pro Phe Ser Ser Tyr Glu Lys Leu Asp20 25 30Ile Thr Val Leu Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO62的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸
(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO62AAGGGGATCG ATTATGAGAA GGTCAAAGAC TACACCATTG AGATTGTGGC TGTGGACTCT 60GGCAACCCCC CACTCTCCAG CACTAACTCC CTCAAGGTGC AGGTGGTGGA CGTCAATGACl20AACGCACCGT G 131(2)SEQ ID NO63的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO63Lys Gly Ile Asp Tyr Glu Lys Val Lys Asp Tyr Thr Ile Glu Ile Val1 5 10 15Ala Val Asp Ser Gly Asn Pro Pro Leu Ser Ser Thr Asn Ser Leu Lys20 25 30Val Gln Val Val Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO64的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型cDNA(xi)序列描述SEQ ID NO64AAGGGACTCG ACTACGAGGA TCGGCGGGAA TTTGAATTAA CAGCTCATAT CAGCGATGGG 60GGCACCCCGG TCCTAGCCAC CAACATCAGC GTGAACATAT TTGTCACTGA TCGCAACGAT120AATGCCCCCG T 131(2)SEQ ID NO65的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO65Lys Gly Leu Asp Tyr Glu Asp Arg Arg Glu Phe Glu Leu Thr Ala His1 5 10 15Ile Ser Asp Gly Gly Thr Pro Val Leu Ala Thr Asn Ile Ser Val Asn20 25 30Ile phe Val Thr Asp Arg Asn Asp Asn Ala Pro35 40(2)SEQ ID NO66的信息(i)序列特征(A)長(zhǎng)度470堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO66AAGGGTTTGG ACTACGAGAC CACACAGGCC TACCAGCTCA CGGTCAACGC CACAGATCAA 60GACAACACCA GGCCTCTGTC CACCCTGGCC AACTTGGCCA TCATCATCAC AGATGTCCAG120GACATGGACC CCATCTTCAT CAACCTGCCT TACAGCACCA ACATCTACGA GCATTCTCCT180CCGGGCACGA CGGTGCGCAT CATCACCGCC ATAGACCAGG ATCAAGGACG TCCCCGGGGC240ATTGGCTACA CCATCGTTTC AGGGAATACC AACAGCATCT TTGCCCTGGA CTACATCAGC300GGAGTGCTGA CCTTGAATGG CCTGCTGGAC CGGGAGAACC CCCTGTACAG CCATGGCTTC360ATCCTGACTG TGAAGGGCAC GGAGCTGAAC GATGACCGCA CCCCATCTGA CGCTACAGTC420ACCACGACCT TCAATATCCT GGTTATTGAC ATCAACGACA ACGCCCCACT 470(2)SEQ ID NO67的信息(i)序列特征(A)長(zhǎng)度156氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO67Lys Gly Leu Asp Tyr Glu Thr Thr Gln Ala Tyr Gln Leu Thr Val Asn1 5 10 15Ala Thr Asp Gln Asp Asn Thr Arg Pro Leu Ser Thr Leu Ala Asn Leu20 25 30Ala Ile Ile Ile Thr Asp Val Gln Asp Met Asp Pro Ile Phe Ile Asn35 40 45Leu Pro Tyr Ser Thr Asn Ile Tyr Glu His Ser Pro Pro Gly Thr Thr50 55 60Val Arg Ile Ile Thr Ala Ile Asp Gln Asp Gln Gly Arg Pro Arg Gly65 70 75 80Ile Gly Tyr Thr Ile Val Ser Gly Asn Thr Asn Ser Ile Phe Ala Leu85 90 95Asp Tyr Ile Ser Gly Val Leu Thr Leu Asn Gly Leu Leu Asp Arg Glu100 105 110Asn Pro Leu Tyr Ser Gly Gly Phe Ile Leu Thr Val Lys Gly Thr Glu115 120 125
Leu Asn Asp Asp Arg Thr Pro Ser Asp Ala Thr Val Thr Thr Thr Phe130 135 140Asn Ile Leu Val Ile Asp Ile Asn Asp Asn Ala Pro145 150 155(2)SEQ ID NO68的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO68AAGGGGGTCG ATTACGAGGT ACTACAGGCC TTTGAGTTCC ACGTGAGCGC CACAGACCGA 60GGCTCACCGG GGCTCAGCAG CCAGGCTCTG GTGCGCGTGG TGGTGCTGGA CGACAATGAC120AACGCTCCCG T 131(2)SEQ ID NO69的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO69Lys Gly Val Asp Tyr Glu Val Leu Gln Ala Phe Glu Phe His Val Ser1 5 10 15Ala Thr Asp Arg Gly Ser Pro Gly Leu Ser Ser Gln Ala Leu Val Arg20 25 30val Val Val Leu Asp Asp Asn Asp Asn Ala Pro35 40(2)SEQ ID NO70的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO70AAGGGGCTGG ATTATGAGCA GTTCCAGACC CTACAACTGG GAGTGACCGC TAGTGACAGT 60GGAAACCCAC CATTAAGAAG CAATATTTCA CTGACCCTTT TCGTGCTGGA CCAGAATGAT120AACGCCCCAA A 131(2)SEQ ID NO71的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO71Lys Gly Leu Asp Tyr Glu Gln phe Gln Thr Leu Gln Leu Gly Val Thr1 5 10 15Ala Ser Asp Ser Gly Asn Pro Pro Leu Arg Ser Asn Ile Ser Leu Thr20 25 30Leu Phe Val Leu Asp Gln Asn Asp Asn Ala pro35 40(2)SEQ ID NO72的信息(i)序列特征
(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO72AAGCGGGTTG ATTACGAGGA TGTCCAGAAA TACTCGCTGA GCATTAAGGC CCAGGATGGG 60CGGCCCCCGC TCATCAATTC TTCAGGGGTG GTGTCTGTGC AGGTGCTGGA TGTCAACGAC120AATGCCCCGG A 131(2)SEQ ID NO73的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型肽(xi)序列描述SEQ ID NO 73Lys Arg Val Asp Tyr Glu Asp Val Gln Lys Tyr Ser Leu Ser Ile Lys1 5 10 15Ala Gln Asp Gly Arg Pro Pro Leu Ile Asn Ser Ser Gly Val Val Ser20 25 30Val Gln Val Leu Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO74的信息(i)序列特征(A)長(zhǎng)度125堿基對(duì)(B)類型核酸
(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO74AAACCGGTAG ACTTTGAGCT ACAGCAGTTC TATGAAGTAG CTGTGGTGGC TTGGAACTCT 60GAGGGATTTC ATGTCAAAAG GGTCATTAAA GTGCAACTTT TAGATGACAA CGACAATGCC120CCGAT125(2)SEQ ID NO75的信息(i)序列特征(A)長(zhǎng)度41氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO75Lys Pro Val Asp Phe Glu Leu Gln Gln Phe Tyr Glu Val Ala Val Val1 5 10 15Ala Trp Asn Ser Glu Gly Phe His Val Lys Arg Val Ile Lys Val Gln20 25 30Leu Leu Asp Asp Asn Asp Asn Ala Pro35 40(2)SEQ ID NO76的信息(i)序列特征(A)長(zhǎng)度125堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型cDNA(xi)序列描述SEQ ID NO76AAGGGATTAG ATTTTGAAAC TTTGCCCATT TACACATTGA TAATACAAGG AACTAACATG 60GCTGGTTTGT CCACTAATAC AACGGTTCTA GTTCACTTGC AGGATGAGAA TGATAACGCC120CCAAA125(2)SEQ ID NO77的信息(i)序列特征(A)長(zhǎng)度41氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO77Lys Gly Leu Asp Phe Glu Thr Leu Pro Ile Tyr Thr Leu Ile Ile Gln1 5 10 15Gly Thr Asn Met Ala Gly Leu Ser Thr Asn Thr Thr Val Leu Val His20 25 30Leu Gln Asp Glu Asn Asp Asn Ala Pro35 40(2)SEQ ID NO78的信息(i)序列特征(A)長(zhǎng)度134堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO78AAGCGGGCGG ATTTCGAGGC GATCCGGGAG TACAGTCTGA GGATCAAAGC GCAGGACGGG60GGGCGGCCTC CCCTCAGCAA CACCACGGGC ATGGTCACAG TGCAGGTCGT GGACGTCAAT 120GACAACGCAC CCCT 134(2)SEQ ID NO79的信息(i)序列特征(A)長(zhǎng)度44氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO79Lys Arg Ala Asp Phe Glu Ala Ile Arg Glu Tyr Ser Leu Arg Ile Lys1 5 10 15Ala Gln Asp Gly Gly Arg Pro Pro Leu Ser Asn Thr Thr Gly Met Val20 25 30Thr Val Gln Val Val Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO80的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO80AAGCGGTTGG ATTACGAAAA GGCATCGGAA TATGAAATCT ATGTTCAAGC CGCTGACAAA60GGCGCTGTCC CTATGGCTGG CCATTGCAAA GTGTTGCTGG AGATCGTGGA TGTCAACGAC 120AACGCCCCCT T131(2)SEQ ID NO81的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO81Lys Arg Leu Asp Tyr Glu Lys Ala Ser Glu Tyr Glu Ile Tyr Val Gln1 5 10 15Ala Ala Asp Lys Gly Ala Val Pro Met Ala Gly His Cys Lys Val Leu20 25 30Leu Glu Ile Val Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO82的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO82AAGGGGATCG ATTATGAGGA TCAGGTCTCT TACACATTAG CAGTAACAGC ACATGACTAT 60GGCATCCCTC AAAAATCAGA CACTACCTAT TTGGAAATCT TAGTAATTGA TGTTAACGAC120AACGCGCCCC A 131(2)SEQ ID NO83的信息(i)序列特征
(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO83Lys Gly Ile Asp Tyr Glu Asp G1n Val Ser Tyr Thr Leu Ala Val Thr1 5 10 15Ala His Asp Tyr Gly Ile Pro Gln Lys Ser Asp Thr Thr Tyr Leu Glu20 25 30Ile Leu Val Ile Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO84的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO84AAAGGGTTAG ATTTCGAGGG CACTAAAGAT TCAGCGTTTA AAATAGTGGC AGCTGACACA 60GGGAAGCCCA GCCTCAACCA GACAGCCCTG GTGAGAGTAG AGCTGGAGGA TGAGAACGAC120AACGCCCCAA T 131(2)SEQ ID NO85的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸
(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO85Lys Gly Leu Asp Phe Glu Gly Thr Lys Asp Ser Ala Phe Lys Ile Val1 5 10 15Ala Ala Asp Thr Gly Lys pro Ser Leu Asn Gln Thr Ala Leu Val Arg20 25 30Val Glu Leu Glu Asp Glu Asn Asp Asn Ala Pro35 40(2)SEQ ID NO86的信息(i)序列特征(A)長(zhǎng)度130堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO86AAGGGTGTGG ATTTTGAAAG TGTGCGTAGC TACAGGCTGG TTATTCGTGC TCAAGATGGA 60GGCAGCCCCT CCAGAAGTAA CACCACCCAG CTCTTGGTCA ACGTCATCGA TCGAATGACA120ATGCGCCGCT 130(2)SEQ ID NO87的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO87Lys Gly Val Asp Phe Glu Ser Val Arg Ser Tyr Arg Leu Val Ile Arg1 5 10 15Ala Gln Asp Gly Gly Ser Pro Ser Arg Ser Asn Thr Thr Gln Leu Leu20 25 30Val Asn Val Ile Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO88的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO88AAGGGTGTGG ACTTCGAGCT GACACATCTG TATGAGATTT GGATTGAGGC TGCCGATGGA 60GACACGCCAA GTCTGCGTAG TGTAACTCTT ATAACGCTCA ACGTAACGGA TGCCAATGAC120AATGCTCCCA A 131(2)SEQ ID NO89的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO89
Lys Gly Val Asp Phe Glu Leu Thr His Leu Tyr Glu Ile Trp Ile Glu1 5 10 15Ala Ala Asp Gly Asp Thr Pro Ser Leu Arg Ser Val Thr Leu Ile Thr20 25 30Leu Asn Val Thr Asp Ala Asn Asp Asn Ala Pro35 40(2)SEQ ID NO90的信息(i)序列特征(A)長(zhǎng)度441堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO90CAAGGCGTTT GATTTTGAAG AGACAAGTAG ATATGTGTTG AGTGTGGAAG CTAAGGATGG 60AGGAGTACAC ACAGCTCACT GTAATGTTCA AATAGAAATT GTTGACGAGA ATGACAATGC 120CCCAGAGGTG ACATTCATGT CCTTCTCTAA CCAGATTCCA GAGGATTCAG ACCTTGGAAC 180TGTAATAGCC CTCATAAAAG TGCGAGACAA GGATTCTGGG CAAAATGGCA TGGTGACATG 240CTATACTCAG GAAGAAGTTC CTTTCAAATT AGAATCCACC TCGAAGAATT ATTACAAGCT 300GGTGATTGCT GGAGCCCTAA ACCGGGAGCA GACAGCAGAC TACAACGTCA CAATCATAGC 360CACCGACAAG GGCAAACCAG CCCTTTCCTC CAGGACAAGC ATCACCGTGC ACATCTCCGA 420CATCAACGAT AATGCCCCCG T 441(2)SEQ ID NO91的信息(i)序列特征(A)長(zhǎng)度146氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO91Lys Ala Phe Asp Phe Glu Glu Thr Ser Arg Tyr Val Leu Ser Val Glu1 5 10 15Ala Lys Asp Gly Gly Val His Thr Ala His Cys Asn Val Gln Ile Glu20 25 30Ile Val Asp Glu Asn Asp Asn Ala Pro Glu Val Thr Phe Met Ser Phe35 40 45Ser Asn Gln Ile Pro Glu Asp Ser Asp Leu Gly Thr Val Ile Ala Leu50 55 60Ile Lys Val Arg Asp Lys Asp Ser Gly Gln Asn Gly Met Val Thr Cys65 70 75 80Tyr Thr Gln Glu Glu Val Pro Phe Lys Leu Glu Ser Thr Ser Lys Asn85 90 95Tyr Tyr Lys Leu Val Ile Ala Gly Ala Leu Asn Arg Glu Gln Thr Ala100 105 110Asp Tyr Asn Val Thr Ile Ile Ala Thr Asp Lys Gly Lys Pro Ala Leu115 120 125Ser Ser Arg Thr Ser Ile Thr Leu His Ile Ser Asp Ile Asn Asp Asn130 135 140Ala Pro145(2)SEQ ID NO92的信息(i)序列特征(A)長(zhǎng)度131堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO92AAGCGAGTGG ATTACGAGGC CACTCGGAAT TATAAGCTGA GAGTTAAGGC TACTGATCTT 60GGGATTCCAC CGAGATCTTC TAACATGACA CTGTTCATTC ATGTCCTTGA TGTTAACGAC 120AACGCTCCCT T 131(2)SEQ ID NO93的信息(i)序列特征(A)長(zhǎng)度43氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO93Lys Arg val Asp Tyr Glu Ala Thr Arg Asn Tyr Lys Leu Arg Val Lys1 5 10 15Ala Thr Asp Leu Gly Ile Pro Pro Arg Ser Ser Asn Met Thr Leu Phe20 25 30Ile His Val Leu Asp Val Asn Asp Asn Ala Pro35 40(2)SEQ ID NO94的信息(i)序列特征(A)長(zhǎng)度4104堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(ix)特征(A)名稱/鍵CDS(B)定位495..3572(xi)序列描述SEQ ID NO94CCTCTATTCG ACATTCTCTT TGGATTGTTT TGCTATAACT TGAAATTTGG GATGTCACAA 60ACGAAACTGT CATCTGTTTC CGCCAAACTG TGGTTCTGCT AATCTCCCAG GCTGGCAGCA 120TTGGAGACTT GCTGACTTCT TTCATCCCCC ACTCTTTTCA CCTGAAATTC CTTTCCTTGG 180TTTTGCTCTA AGTCCTATGC TTCAGTCAGG GGCCAACCAA ATCTCACTGC CTCCTTTTTA 240TCATGAAGCC TTTGATCACT GATAGTTCTT TTTATATCTT GAAAAATCAC CCTTCCCAGT 300ACAGTTAATA TTTAGTATCT CTACTCATCT TGGCACTTAC TCACAGCTCC ATAATTCAGT 360CGTTTTCGTA CCTCTTCATG GTGATGGGGA GCCCTTTGGA GGTGGTGACT GTGCTTTATA 420CTCCTCATGA TGCTTCACAT GTGGCAGGCG TGGAGTGCCC GGAGGCGGCC CTCCTGATTC 480TGGGGCCTCC CAGG ATG GAG CCC CTG AGG CAC AGC CCA GGC CCT GGG GGG530Met Glu Pro Leu Arg His Ser Pro Gly Pro Gly Gly1 5 10CAA CGG CTA CTG CTG CCC TCC ATG CTG CTA GCA CTG CTG CTC CTG CTG578Gln Arg Leu Leu Leu Pro Ser Met Leu Leu Ala Leu Leu Leu Leu Leu15 20 25GCT CCA TCC CCA GGC CAC GCC ACT CGG GTA GTG TAC AAG GTG CCG GAG626Ala Pro Ser Pro Gly His Ala Thr Arg Val Val Tyr Lys Val Pro Glu30 35 40GAA CAG CCA CCC AAC ACC CTC ATT GGG AGC CTC GCA GCC GAC TAT GGT674Glu Gln Pro Pro Asn Thr Leu Ile Gly Ser Leu Ala Ala Asp Tyr Gly45 50 55 60TTT CCA GAT GTG GGG CAC CTG TAC AAG CTA GAG GTG GGT GCC CCG TAC722Phe Pro Asp Val Gly His Leu Tyr Lys Leu Glu Val Gly Ala Pro Tyr65 70 75CTT CGC GTG GAT GGC AAG ACA GGT GAC ATT TTC ACC ACC GAG ACC TCC770Leu Arg Val Asp Gly Lys Thr Gly Asp Ile Phe Thr Thr Glu Thr Ser80 85 90ATC GAC CGT GAG GGG CTC CGT GAA TGC CAG AAC CAG CTC CCT GGT GAT818Ile Asp Arg Glu Gly Leu Arg Glu Cys Gln Asn Gln Leu Pro Gly Asp95 100 105CCC TGC ATC CTG GAG TTT GAG GTA TCT ATC ACA GAC CTC GTG CAG AAT866Pro Cys Ile Leu Glu Phe Glu Val Ser Ile Thr Asp Leu Val Gln Asn110 115 120GCG AGC CCC CGG CTG CTA GAG GGC CAG ATA GAA GTA CAA GAC ATC AAT914Ala Ser Pro Arg Leu Leu Glu Gly Gln Ile Glu Val Gln Asp Ile Asn125 130 135 140GAC AAC ACA CCC AAC TTC GCC TCA CCA GTC ATC ACT CTG GCC ATC CCT962Asp Asn Thr Pro Asn Phe Ala Ser Pro Val Ile Thr Leu Ala Ile Pro145 150 155GAG AAC ACC AAC ATC GGC TCA CTC TTC CCC ATC CCG CTG GCT TCA GAC 1010Glu Asn Thr Asn Ile Gly Ser Leu Phe Pro Ile Pro Leu Ala Ser Asp160 165 170CGT GAT GCT GGT CCC AAC GGT GTG GCA TCC TAT GAG CTG CAG GTG GCA 1058Arg Asp Ala Gly Pro Asn Gly Val Ala Ser Tyr Glu Leu Gln Val Ala175 180 185GAG GAC CAG GAG GAG AAG CAA CCA CAG CTC ATT GTG ATG GGC AAC CTG 1106Glu Asp Gin Glu Glu Lys Gln Pro Gln Leu Ile Val Met Gly Asn Leu190 195 200GAC CGT GAG CGC TGG GAC TCC TAT GAC CTC ACC ATC AAG GTG CAG GAT 1154Asp Arg Glu Arg Trp Asp Ser Tyr Asp Leu Thr Ile Lys Val Gln Asp205 210 215 220GGC GGC AGC CCC CCA CGC GCC ACG AGT GCC CTG CTG CGT GTC ACC GTG 1202Gly Gly Ser Pro Pro Arg Ala Thr Ser Ala Leu Leu Arg Val Thr Val225 230 235CTT GAC ACC AAT GAC AAC GCC CCC AAG TTT GAG CGG CCC TCC TAT GAG 1250Leu Asp Thr Asn Asp Asn Ala Pro Lys Phe Glu Arg Pro Ser Tyr Glu240 245 250GCC GAA CTA TCT GAG AAT AGC CCC ATA GGC CAC TCG GTC ATC CAG GTG 1298Ala Glu Leu Ser Glu Asn Ser Pro Ile Gly His Ser Val Ile Gln Val255 260 265AAG GCC AAT GAC TCA GAC CAA GGT GCC AAT GCA GAA ATC GAA TAC ACA 1346Lys Ala Asn Asp Ser Asp Gln Gly Ala Asn Ala Glu Ile Glu Tyr Thr270 275 280TTC CAC CAG GCG CCC GAA GTT GTG AGG CGT CTT CTT CGA CTG GAC AGG 1394Phe His Gln Ala Pro Glu Val Val Arg Arg Leu Leu Arg Leu Asp Arg285 290 295 300AAC ACT GGA CTT ATC ACT GTT CAG GGC CCG GTG GAC CGT GAG GAC CTA 1442Asn Thr Gly Leu Ile Thr Val Gln Gly Pro Val Asp Arg Glu Asp Leu305 310 315AGC ACC CTG CGC TTC TCA GTG CTT GCT AAG GAC CGA GGC ACC AAC CCC 1490Ser Thr Leu Arg Phe Ser Val Leu Ala Lys Asp Arg Gly Thr Asn Pro320 325 330AAG AGT GCC CGT GCC CAG GTG GTT GTG ACC GTG AAG GAC ATG AAT GAC 1538Lys Ser Ala Arg Ala Gln Val Val Val Thr Val Lys Asp Met Asn Asp335 340 345AAT GCC CCC ACC ATT GAG ATC CGG GGC ATA GGG CTA GTG ACT CAT CAA 1586Asn Ala Pro Thr Ile Glu Ile Arg Gly Ile Gly Leu Val Thr His Gln350 355 360GAT GGG ATG GCT AAC ATC TCA GAG GAT GTG GCA GAG GAG ACA GCT GTG 1634Asp Gly Met Ala Asn Ile Ser Glu Asp Val Ala Glu Glu Thr Ala Val365 370 375 380GCC CTG GTG CAG GTG TCT GAC CGA GAT GAG GGA GAG AAT GCA GCT GTC 1682Ala Leu Val Gln Val Ser Asp Arg Asp Glu Gly Glu Asn Ala Ala Val385 390 395ACC TGT GTG GTG GCA GGT GAT GTG CCC TTC CAG CTG CGC CAG GCC AGT 1730Thr Cys Val Val Ala Gly Asp Val Pro Phe Gln Leu Arg Gln Ala Ser400 405 410GAG ACA GGC AGT GAC AGC AAG AAG AAG TAT TTC CTG CAG ACT ACC ACC 1778Glu Thr Gly Ser Asp Ser Lys Lys Lys Tyr Phe Leu Gln Thr Thr Thr415 420 425CCG CTA GAC TAC GAG AAG GTC AAA GAC TAC ACC ATT GAG ATT GTG GCT 1826Pro Leu Asp Tyr Glu Lys Val Lys Asp Tyr Thr Ile Glu Ile Val Ala430 435 440GTG GAC TCT GGC AAC CCC CCA CTC TCC AGC ACT AAC TCC CTC AAG GTG 1874Val Asp Ser Gly Asn Pro Pro Leu Ser Ser Thr Asn Ser Leu Lys Val445 450 455 460CAG GTG GTG GAC GTC AAT GAC AAC GCA CCT GTC TTC ACT CAG AGT GTC 1922Gln Val Val Asp Val Asn Asp Asn Ala Pro Val Phe Thr Gln Ser Val465 470 475ACT GAG GTC GCC TTC CCG GAA AAC AAC AAG CCT GGT GAA GTG ATT GCT 1970Thr Glu Val Ala Phe Pro Glu Asn Asn Lys Pro Gly Glu Val Ile Ala480 485 490GAG ATC ACT GCC AGT GAT GCT GAC TCT GGC TCT AAT GCT GAG CTG GTT 2018Glu Ile Thr Ala Ser Asp Ala Asp Ser Gly Ser Asn Ala Glu Leu Val495 500 505TAC TCT CTG GAG CCT GAG CCG GCT GCT AAG GGC CTC TTC ACC ATC TCA 2066Tyr Ser Leu Glu Pro Glu Pro Ala Ala Lys Gly Leu Phe Thr Ile Ser510 515 520CCC GAG ACT GGA GAG ATC CAG GTG AAG ACA TCT CTG GAT CGG GAA CAG 2114Pro Glu Thr Gly Glu Ile Gln Val Lys Thr Ser Leu Asp Arg Glu Gln525 530 535 540CGG GAG AGC TAT GAG TTG AAG GTG GTG GCA GCT GAC CGG GGC AGT CCT 2162Arg Glu Ser Tyr Glu Leu Lys Val Val Ala Ala Asp Arg Gly Ser Pro545 550 555AGC CTC CAG GGC ACA GCC ACT GTC CTT GTC AAT GTG CTG GAC TGC AAT 2210Ser Leu Gln Gly Thr Ala Thr Val Leu Val Asn Val Leu Asp Cys Asn560 565 570GAC AAT GAC CCC AAA TTT ATG CTG AGT GGC TAC AAC TTC TCA GTG ATG 2258Asp Asn Asp Pro Lys Phe Met Leu Ser Gly Tyr Asn Phe Ser Val Met575 580 585GAG AAC ATG CCA GCA CTG AGT CCA GTG GGC ATG GTG ACT GTC ATT GAT 2306Glu Asn Met Pro Ala Leu Ser Pro Val Gly Met Val Thr Val Ile Asp590 595 600GGA GAC AAG GGG GAG AAT GCC CAG GTG CAG CTC TCA GTG GAG CAG GAC 2354Gly Asp Lys Gly Glu Asn Ala Gln Val Gln Leu Ser Val Glu Gln Asp605 610 615 620AAC GGT GAC TTT GTT ATC CAG AAT GGC ACA GGC ACC ATC CTA TCC AGC 2402Asn Gly Asp Phe Val Ils Gln Asn Gly Thr Gly Thr Ile Leu Ser Ser625 630 635CTG AGC TTT GAT CGA GAG CAA CAA AGC ACC TAC ACC TTC CAG CTG AAG 2450Leu Ser Phe Asp Arg Glu Gln Gln Ser Thr Tyr Thr Phe Gln Leu Lys640 645 650GCA GTG GAT GGT GGC GTC CCA CCT CGC TCA GCT TAC GTT GGT GTC ACC2498Ala Val Asp Gly Gly Val Pro Pro Arg Ser Ala Tyr Val Gly Val Thr655 660 665ATC AAT GTG CTG GAC GAG AAT GAC AAC GCA CCC TAT ATC ACT GCC CCT2546Ile Asn Val Leu Asp Glu Asn Asp Asn Ala Pro Tyr Ile Thr Ala Pro670 675 680TCT AAC ACC TCT CAC AAG CTG CTG ACC CCC CAG ACA CGT CTT GGT GAG2594Ser Asn Thr Ser His Lys Leu Leu Thr Pro Gln Thr Arg Leu Gly Glu685 690 695 700ACG GTC AGC CAG GTG GCA GCC GAG GAC TTT GAC TCT GGT GTC AAT GCC2642Thr Val Ser Gln Val Ala Ala Glu Asp Phe Asp Ser Gly Val Asn Ala705 710 715GAG CTG ATC TAC AGC ATT GCA GGT GGC AAC CCT TAT GGA CTC TTC CAG2690Glu Leu Ile Tyr Ser Ile Ala Gly Gly Asn Pro Tyr Gly Leu Phe Gln720 725 730ATT GGG TCA CAT TCA GGT GCC ATC ACC CTG GAG AAG GAG ATT GAG CGG2738Ile Gly Ser His Ser Gly Ala Ile Thr Leu Glu Lys Glu Ile Glu Arg735 740 745CGC CAC CAT GGG CTA CAC CGC CTG GTG GTG AAG GTC AGT GAC CGC GGC2786Arg His His Gly Leu His Arg Leu Val Val Lys Val Ser Asp Arg Gly750 755 760AAG CCC CCA CGC TAT GGC ACA GCC TTG GTC CAT CTT TAT GTC AAT GAG2834Lys Pro Pro Arg Tyr Gly Thr Ala Leu Val His Leu Tyr Val Asn Glu765 770 775 780ACT CTG GCC AAC CGC ACG CTG CTG GAG ACC CTC CTG GGC CAC AGC CTG2882Thr Leu Ala Asn Arg Thr Leu Leu Glu Thr Leu Leu Gly His Ser Leu785 790 795GAC ACG CCG CTG GAT ATT GAC ATT GCT GGG GAT CCA GAA TAT GAG CGC2930Aap Thr Pro Leu Asp Ile Asp Ile Ala Gly Asp Pro Glu Tyr Glu Arg800 805 810TCC AAG CAG CGT GGC AAC ATT CTC TTT GGT GTG GTG GCT GGT GTG GTG2978Ser Lys Gln Arg Gly Asn Ile Leu Phe Gly Val Val Ala Gly Val Val815 820 825GCC GTG GCC TTG CTC ATC GCC CTG GCG GTT CTT GTG CGC TAC TGC AGA3026Ala Val Ala Leu Leu Ile Ala Leu Ala Val Leu Val Arg Tyr Cys Arg830 835 840CAG CGG GAG GCC AAA AGT GGT TAC CAG GCT GGT AAG AAG GAG ACC AAG3074Gln Arg Glu Ala Lys Ser Gly Tyr Gln Ala Gly Lys Lys Glu Thr Lys845 850 855 860GAC CTG TAT GCC CCC AAG CCC AGT GGC AAG GCC TCC AAG GGA AAC AAA3122Asp Leu Tyr Ala Pro Lys Pro Ser Gly Lys Ala Ser Lys Gly Asn Lys865 870 875AGC AAA GGC AAG AAG AGC AAG TCC CCA AAG CCC GTG AAG CCA GTG GAG3170Ser Lys Gly Lys Lys Ser Lys Ser Pro Lys Pro Val Lys Pro Val Glu880 885 890GAC GAG GAT GAG GCC GGG CTG CAG AAG TCC CTC AAG TTC AAC CTG ATG3218Asp Glu Asp Glu Ala Gly Leu Gln Lys Ser Leu Lys Phe Aen Leu Met895 900 905AGC GAT GCC CCT GGG GAC AGT CCC CGC ATC CAC CTG CCC CTC AAC TAC3266Ser Asp Ala Pro Gly Asp Ser Pro Arg Ile His Leu Pro Leu Asn Tyr910 915 920CCA CCA GGC AGC CCT GAC CTG GGC CGC CAC TAT CGC TCT AAC TCC CCA3314Pro Pro Gly Ser Pro Asp Leu Gly Arg His Tyr Arg Ser Asn Ser Pro925 930 935 940CTG CCT TCC ATC CAG CTG CAG CCC CAG TCA CCC TCA GCC TCC AAG AAG3362Leu Pro Ser Ile Gln Leu Gln Pro Gln Ser Pro Ser Ala Ser Lys Lys945 950 955CAC CAG GTG GTA CAG GAC CTG CCA CCT GCA AAC ACA TTC GTG GGC ACC3410His Gln Val Val Gln Asp Leu Pro Pro Ala Asn Thr Phe Val Gly Thr960 965 970GGG GAC ACC ACG TCC ACG GGC TCT GAG CAG TAC TCC GAC TAC AGC TAC3458Gly Asp Thr Thr Ser Thr Gly Ser Glu Gln Tyr Ser Asp Tyr Ser Tyr975 980 985CGC ACC AAC CCC CCC AAA TAC CCC AGC AAG CAG GTA GGC CAG CCC TTT3506Arg Thr Asn Pro Pro Lys Tyr Pro Ser Lys Gln Val Gly Gln Pro Phe990 995 1000CAG CTC AGC ACA CCC CAG CCC CTA CCC CAC CCC TAC CAC GGA GCC ATC3554Gln Leu Ser Thr Pro Gln Pro Leu Pro His Pro Tyr His Gly Ala Ile1005101010151020TGG ACC GAG GTG TGG GAG TGATGGAGCA GGTTTACTGT GCCTGCCCGT 3602Trp Thr Glu Val Trp Glu1025GTTGGGGGCC AGCCTGAGCC AGCAGTGGGA GGTGGGGCCT TAGTGCCTCA CCGGGCACAC 3662GGATTAGGCT GAGTGAAGAT TAAGGGAGGG TGTGCTCTGT GGTCTCCTCC CTGCCCTCTC 3722CCCACTGGGG AGAGACCTGT GATTTGCCAA GTCCCTGGAC CCTGGACCAG CTACTGGGCC 3782TTATGGGTTG GGGGTGGTAG GCAGGTGAGC GTAAGTGGGG AGGGAAATGG GTAAGAAGTC 3842TACTCCAAAC CTAGGTCTCT ATGTCAGACC AGACCTAGGT GCTTCTCTAG GAGGGAAACA 3902GGGAGACCTG GGGTCCTGTG GATAACTGAG TGGGGAGTCT GCCAGGGGAG GGCACCTTCC 3962CATTGTGCCT TCTGTGTGTA TTGTGCATTA ACCTCTTCCT CACCACTAGG CTTCTGGGGC 4022TGGGTCCCAC ATGCCCTTGA CCCTGACAAT AAAGTTCTCT ATTTTTGGAA AAAAAAAAAA 4082AAAAAAAAAA AAAAAAAAAA AA 4104(2)SEQ ID NO95的信息(i)序列特征(A)長(zhǎng)度1026氨基酸(B)類型氨基酸(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO95Met Glu Pro Leu Arg His Ser Pro Gly Pro Gly Gly Gln Arg Leu Leu1 5 10 15Leu Pro Ser Met Leu Leu Ala Leu Leu Leu Leu Leu Ala Pro Ser Pro20 25 30Gly His Ala Thr Arg Val Val Tyr Lys Val Pro Glu Glu Gln Pro Pro35 40 45Asn Thr Leu Ile Gly Ser Leu Ala Ala Asp Tyr Gly Phe Pro Asp Val50 55 60Gly His Leu Tyr Lys Leu Glu Val Gly Ala Pro Tyr Leu Arg val Asp65 70 75 80Gly Lys Thr Gly Asp Ile Phe Thr Thr Glu Thr Ser Ile Asp Arg Glu85 90 95Gly Leu Arg Glu Cys Gln Asn Gln Leu Pro Gly Asp Pro Cys Ile Leu100 105 110Glu Phe Glu Val Ser Ile Thr Asp Leu Val Gln Asn Ala Ser Pro Arg115 120 125Leu Leu Glu Gly Gln Ile Glu Val Gln Asp Ile Asn Asp Asn Thr Pro130 135 140Asn Phe Ala Ser Pro Val Ile Thr Leu Ala Ile Pro Glu Asn Thr Asn145 150 155 160Ile Gly Ser Leu Phe Pro Ile Pro Leu Ala Ser Asp Arg Asp Ala Gly165 170 175Pro Asn Gly Val Ala Ser Tyr Glu Leu Gln Val Ala Glu Asp Gln Glu180 185 190Glu Lys Gln Pro Gln Leu Ile Val Met Gly Asn Leu Asp Arg Glu Arg195 200 205Trp Asp Ser Tyr Asp Leu Thr Ile Lys Val Gln Asp Gly Gly Ser Pro210 215 220Pro Arg Ala Thr Ser Ala Leu Leu Arg Val Thr Val Leu Asp Thr Asn225 230 235 240Asp Asn Ala Pro Lys Phe Glu Arg Pro Ser Tyr Glu Ala Glu Leu Ser245 250 255Glu Asn Ser Pro Ile Gly His Ser Val Ile Gln Val Lye Ala Asn Asp260 265 270
Ser Asp Gln Gly Ala Asn Ala Glu Ile Glu Tyr Thr Phe His Gln Ala275 280 285Pro Glu Val Val Arg Arg Leu Leu Arg Leu Asp Arg Asn Thr Gly Leu290 295 300Ile Thr Val Gln Gly Pro Val Asp Arg Glu Asp Leu Ser Thr Leu Arg305 310 315 320Phe Ser Val Leu Ala Lys Asp Arg Gly Thr Asn Pro Lys Ser Ala Arg325 330 335Ala Gln Val Val Val Thr Val Lys Asp Met Asn Asp Asn Ala Pro Thr340 345 350Ile Glu Ile Arg Gly Ile Gly Leu Val Thr His Gln Asp Gly Met Ala355 360 365Asn Ile Ser Glu Aep Val Ala Glu Glu Thr Ala Val Ala Leu Val Gln370 375 380Val Ser Asp Arg Asp Glu Gly Glu Asn Ala Ala Val Thr Cys Val Val385 390 395 400Ala Gly Asp Val Pro Phe Gln Leu Arg Gln Ala Ser Glu Thr Gly Ser405 410 415Asp Ser Lys Lys Lys Tyr Phe Leu Gln Thr Thr Thr Pro Leu Asp Tyr420 425 430Glu Lys Val Lys Asp Tyr Thr Ile Glu Ile Val Ala Val Asp Ser Gly435 440 445Asn Pro Pro Leu Ser Ser Thr Asn Ser Leu Lys Val Gln Val Val Asp450 455 460Val Asn Asp Asn Ala Pro Val Phe Thr Gln Ser Val Thr Glu Val Ala465 470 475 480Phe Pro Glu Asn Asn Lys Pro Gly Glu Val Ile Ala Glu Ile Thr Ala485 490 495Ser Asp Ala Asp Ser Gly Ser Asn Ala Glu Leu Val Tyr Ser Leu Glu500 505 510Pro Glu Pro Ala Ala Lys Gly Leu Phe Thr Ile Ser Pro Glu Thr Gly515 520 525Glu Ile Gln Val Lys Thr Ser Leu Asp Arg Glu Gln Arg Glu Ser Tyr530 535 540Glu Leu Lys Val Val Ala Ala Asp Arg Gly Ser Pro Ser Leu Gln Gly545 550 555 560Thr Ala Thr Val Leu Val Asn Val Leu Asp Cys Asn Asp Asn Asp Pro565 570 575Lys Phe Met Leu Ser Gly Tyr Asn Phe Ser Val Met Glu Asn Met Pro580 585 590
Ala Leu Ser Pro Val Gly Met Val Thr Val Ile Asp Gly Asp Lys Gly595 600 605Glu Asn Ala Gln Val Gln Leu Ser Val Glu Gln Asp Asn Gly Asp Phe610 615 620Val Ile Gln Asn Gly Thr Gly Thr Ile Leu Ser Ser Leu Ser Phe Asp625 630 635 640Arg Glu Gln Gln Ser Thr Tyr Thr Phe Gln Leu Lys Ala Val Asp Gly645 650 655Gly Val Pro Pro Arg Ser Ala Tyr Val Gly Val Thr Ile Asn Val Leu660 665 670Asp Glu Asn Asp Asn Ala Pro Tyr Ile Thr Ala Pro Ser Asn Thr Ser675 680 685His Lys Leu Leu Thr Pro Gln Thr Arg Leu Gly Glu Thr Val Ser Gln690 695 700Val Ala Ala Glu Asp Phe Asp Ser Gly Val Asn Ala Glu Leu Ile Tyr705 710 715 720Ser Ile Ala Gly Gly Asn Pro Tyr Gly Leu Phe Gln Ile Gly Ser Mis725 730 735Ser Gly Ala Ile Thr Leu Glu Lys Glu Ile Glu Arg Arg His His Gly740 745 750Leu His Arg Leu Val Val Lys Val Ser Asp Arg Gly Lys Pro Pro Arg755 760 765Tyr Gly Thr Ala Leu Val His Leu Tyr Val Asn Glu Thr Leu Ala Asn770 775 780Arg Thr Leu Leu Glu Thr Leu Leu Gly His Ser Leu Asp Thr Pro Leu785 790 795 800Asp Ile Asp Ile Ala Gly Asp Pro Glu Tyr Glu Arg Ser Lys Gln Arg805 810 815Gly Asn Ile Leu Phe Gly Val val Ala Gly Val Val Ala Val Ala Leu820 825 830Leu Ile Ala Leu Ala Val Leu Val Arg Tyr Cys Arg Gln Arg Glu Ala835 840 845Lys Ser Gly Tyr Gln Ala Gly Lys Lys Glu Thr Lys Asp Leu Tyr Ala850 855 860Pro Lys Pro Ser Gly Lys Ala Ser Lys Gly Asn Lys Ser Lys Gly Lys865 870 875 880Lys Ser Lys Ser Pro Lys Pro Val Lys Pro Val Glu Asp Glu Asp Glu885 890 895Ala Gly Leu Gln Lys Ser Leu Lys Phe Asn Leu Met Ser Asp Ala Pro900 905 910
Gly Asp Ser Pro Arg Ile His Leu Pro Leu Asn Tyr Pro Pro Gly Ser915 920 925Pro Asp Leu Gly Arg Hia Tyr Arg Ser Asn Ser Pro Leu Pro Ser Ile930 935 940Gln Leu Gln Pro Gln Ser Pro Ser Ala Ser Lys Lys His Gln Val Val945 950 955 960Gln Asp Leu Pro Pro Ala Asn Thr Phe Val Gly Thr Gly Asp Thr Thr965 970 975Ser Thr Gly Ser Glu Gln Tyr Ser Asp Tyr Ser Tyr Arg Thr Asn Pro980 985 990Pro Lys Tyr Pro Ser Lys Gln Val Gly Gln Pro Phe Gln Leu Ser Thr995 10001005Pro Gln Pro Leu Pro His Pro Tyr His Gly Ala Ile Trp Thr Glu Val101010151020Trp Glu1025(2)SEQ ID NO96的信息(i)序列特征(A)長(zhǎng)度4705堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(ix)特征(A)名稱/鍵CDS(B)定位115..2827(xi)序列描述SEQ ID NO96CGAAAGCCAT GTCGGACTCG TCGCCCAGCG CCCAAGCGCT AACCCGCTGA AAGTTTCTCA 60GCGAAATCTC AGGGACGATC TGGACCCCGC TGAGAGGAAC TGCTTTTGAG TGAG ATG117Met1GTC CCA GAG GCC TGG AGG AGC GGA CTG GTA AGC ACC GGG AGG GTA GTG165Val Pro Glu Ala Trp Arg Ser Gly Leu Val Ser Thr Gly Arg Val Val5 10 15GGA GTT TTG CTT CTG CTT GGT GCC TTG AAC AAG GCT TCC ACG GTC ATT213Gly Val Leu Leu Leu Leu Gly Ala Leu Asn Lys Ala Ser Thr Val Ile20 25 30CAC TAT GAG ATC CCG GAG GAA AGA GAG AAG GGT TTC GCT GTG GGC AAC261His Tyr Glu Ile Pro Glu Glu Arg Glu Lys Gly Phe Ala Val Gly Asn35 40 45GTG GTG GCG AAC CTT GGT TTG GAT CTC GGT AGC CTC TCA GCC CGC AGG309Va1 Val Ala Asn Leu Gly Leu Asp Leu Gly Ser Leu Ser Ala Arg Arg50 55 60 65TTC CCG GTG GTG TCT GGA GCT AGC CGA AGA TTC TTT GAG GTG AAC CGG357Phe Pro Val Val Ser Gly Ala Ser Arg Arg Phe Phe Glu Val Asn Arg70 75 80GAG ACC GGA GAG ATG TTT GTG AAC GAC CGT CTG GAT CGA GAG GAG CTG405Glu Thr Gly Glu Met Phe Val Asn Asp Arg Leu Asp Arg Glu Glu Leu85 90 95TGT GGG ACA CTG CCC TCT TGC ACT GTA ACT CTG GAG TTG GTA GTG GAG453Cys Gly Thr Leu Pro Ser Cys Thr Val Thr Leu Glu Leu Val Val Glu100 105 110AAC CCG CTG GAG CTG TTC AGC GTG GAA GTG GTG ATC CAG GAC ATC AAC501Ash Pro Leu Glu Leu Phe Ser Val Glu Val Val Ile Gln Asp Ile Asn115 120 125GAC AAC AAT CCT GCT TTC CCT ACC CAG GAA ATG AAA TTG GAG ATT AGC549Asp Asn Asn Pro Ala Phe Pro Thr Gln Glu Met Lys Leu Glu Ile Ser130 135 140 145GAG GCC GTG GCT CCG GGG ACG CGC TTT CCG CTC GAG AGC GCG CAC GAT597Glu Ala Val Ala Pro Gly Thr Arg Phe Pro Leu Glu Ser Ala His Asp150 155 160CCC GAT CTG GGA AGC AAC TCT TTA CAA ACC TAT GAG CTG AGC CGA AAT645Pro Asp Leu Gly Ser Asn Ser Leu Gln Thr Tyr Glu Leu Ser Arg Asn165 170 175GAA TAC TTT GCG CTT CGC GTG CAG ACG CGG GAG GAC AGC ACC AAG TAC693Glu Tyr Phe Ala Leu Arg Val Gln Thr Arg Glu Asp Ser Thr Lys Tyr180 185 190GCG GAG CTG GTG TTG GAG CGC GCC CTG GAC CGA GAA CGG GAG CCT AGT741Ala Glu Leu Val Leu Glu Arg Ala Leu Asp Arg Glu Arg Glu Pro Ser195 200 205CTC CAG TTA GTG CTG ACG GCG TTG GAC GGA GGG ACC CCA GCT CTC TCC789Leu Gln Leu Val Leu Thr Ala Leu Asp Gly Gly Thr Pro Ala Leu Ser210 215 220 225GCC AGC CTG CCT ATT CAC ATC AAG GTG CTG GAC GCG AAT GAC AAT GCG837Ala Ser Leu Pro Ile His Ile Lys Val Leu Asp Ala Asn Asp Asn Ala230 235 240CCT GTC TTC AAC CAG TCC TTG TAC CGG GCG CGC GTT CCT GGA GGA TGC885Pro Val Phe Asn Gln Ser Leu Tyr Arg Ala Arg Val Pro Gly Gly Cys245 250 255ACC TCC GGC ACG CGC GTG GTA CAA GTC CTT GCA ACG GAT CTG GAT GAA933Thr Ser Gly Thr Arg Val Val Gln Val Leu Ala Thr Asp Leu Asp Glu260 265 270GGC CCC AAC GGT GAA ATT ATT TAC TCC TTC GGC AGC CAC AAC CGC GCC981Gly Pro Asn Gly Glu Ile Ile Tyr Ser Phe Gly Ser His Asn Arg Ala275 280 285GGC GTG CGG CAA CTA TTC GCC TTA GAC CTT GTA ACC GGG ATG CTG ACA1029Gly Val Arg Gln Leu Phe Ala Leu Asp Leu Val Thr Gly Met Leu Thr290 295 300 305ATC AAG GGT CGG CTG GAC TTC GAG GAC ACC AAA CTC CAT GAG ATT TAC1077Ile Lys Gly Arg Leu Asp Phe Glu Asp Thr Lys Leu His Glu Ile Tyr310 315 320ATC CAG GCC AAA GAC AAG GGC GCC AAT CCC GAA GGA GCA CAT TGC AAA1125Ile Gln Ala Lye Asp Lys Gly Ala Asn Pro Glu Gly Ala His Cys Lys325 330 335GTG TTG GTG GAG GTT GTG GAT GTG AAT GAC AAC GCC CCG GAG ATC ACA1173Val Leu Val Glu Val Val Asp Val Asn Asp Asn Ala Pro Glu Ile Thr340 345 350GTC ACC TCC GTG TAC AGC CCA GTA CCC GAG GAT GCC TCT GGG ACT GTC1221Val Thr Ser Val Tyr Ser Pro Val Pro Glu Asp Ala Ser Gly Thr Val355 360 365ATC GCT TTG CTC AGT GTG ACT GAC CTG GAT GCT GGC GAG AAC GGG CTG1269Ile Ala Leu Leu Ser Val Thr Asp Leu Asp Ala Gly Glu Asn Gly Leu370 375 380 385GTG ACC TGC GAA GTT CCA CCG GGT CTC CCT TTC AGC CTT ACT TCT TCC1317Val Thr Cys Glu Val Pro Pro Gly Leu Pro Phe Ser Leu Thr Ser Ser390 395 400CTC AAG AAT TAC TTC ACT TTG AAA ACC AGT GCA GAC CTG GAT CGG GAG1365Leu Lys Ash Tyr Phe Thr Leu Lys Thr Ser Ala Asp Leu Asp Arg Glu405 410 415ACT GTG CCA GAA TAC AAC CTC AGC ATC ACC GCC CGA GAC GCC GGA ACC1413Thr Val Pro Glu Tyr Asn Leu Ser Ile Thr Ala Arg Asp Ala Gly Thr420 425 430CCT TCC CTC TCA GCC CTT ACA ATA GTG CGT GTT CAA GTG TCC GAC ATC1461Pro Ser Leu Ser Ala Leu Thr Ile Val Arg Val Gln Val Ser Asp Ile435 440 445AAT GAC AAC CCT CCA CAA TCT TCT CAA TCT TCC TAC GAC GTT TAC ATT1509Asn Asp Asn Pro Pro Gln Ser Ser Gln Ser Ser Tyr Asp Val Tyr Ile450 455 460 465GAA GAA AAC AAC CTC CCC GGG GCT CCA ATA CTA AAC CTA AGT GTC TGG1557Glu Glu Asn Asn Leu Pro Gly Ala Pro Ile Leu Asn Leu Ser Val Trp470 475 480GAC CCC GAC GCC CCG CAG AAT GCT CGG CTT TCT TTC TTT CTC TTG GAG1605Asp Pro Asp Ala Pro Gln Asn Ala Arg Leu Ser Phe Phe Leu Leu Glu485 490 495CAA GGA GCT GAA ACC GGG CTA GTG GGT CGC TAT TTC ACA ATA AAT CGT1653Gln Gly Ala Glu Thr Gly Leu Val Gly Arg Tyr Phe Thr Ile Asn Arg500 505 510GAC AAT GGC ATA GTG TCA TCC TTA GTG CCC CTA GAC TAT GAG GAT CGG1701Asp Asn Gly Ile Val Ser Ser Leu Val Pro Leu Asp Tyr Glu Asp Arg515 520 525CGG GAA TTT GAA TTA ACA GCT CAT ATC AGC GAT GGG GGC ACC CCG GTC 1749Arg Glu Phs Glu Leu Thr Ala His Ils Ser Asp Gly Gly Thr Pro Val530 535 540 545CTA GCC ACC AAC ATC AGC GTG AAC ATA TTT GTC ACT GAT CGC AAT GAC 1797Leu Ala Thr Asn Ils Ser Val Asn Ils Phs Val Thr Asp Arg Asn Asp550 555 560AAT GCC CCC CAG GTC CTA TAT CCT CGG CCA GGT GGG AGC TCG GTG GAG 1845Asn Ala Pro Gln Val Leu Tyr Pro Arg Pro Gly Gly Ser Ser Val Glu565 570 575ATG CTG CCT CGA GGT ACC TCA GCT GGC CAC CTA GTG TCA CGG GTG GTA 1893Met Leu Pro Arg Gly Thr Ser Ala Gly His Leu Val Ser Arg Val Val580 585 590GGC TGG GAC GCG GAT GCA GGG CAC AAT GCC TGG CTC TCC TAC AGT CTC 1941Gly Trp Asp Ala Asp Ala Gly His Asn Ala Trp Leu Ser Tyr Ser Leu595 600 605TTT GGA TCC CCT AAC CAG AGC CTT TTT GCC ATA GGG CTG CAC ACT GGT 1989Phs Gly Ser Pro Asn Gln Ser Leu Phs Ala Ile Gly Leu His Thr Gly610 615 620 625CAA ATC AGT ACT GCC CGT CCA GTC CAA GAC ACA GAT TCA CCC AGG CAG 2037Gln Ils Ser Thr Ala Arg Pro Val Gln Asp Thr Asp Ser Pro Arg Gln630 635 640ACT CTC ACT GTC TTG ATC AAA GAC AAT GGG GAG CCT TCG CTC TCC ACC 2085Thr Leu Thr Val Leu Ile Lys Asp Asn Gly Glu Pro Ser Leu Ser Thr645 650 655ACT GCT ACC CTC ACT GTG TCA GTA ACC GAG GAC TCT CCT GAA GCC CGA 2133Thr Ala Thr Leu Thr Val Ser Val Thr Glu Asp Ser Pro Glu Ala Arg660 665 670GCC GAG TTC CCC TCT GGC TCT GCC CCC CGG GAG CAG AAA AAA AAT CTC 2181Ala Glu Phs Pro Ser Gly Ser Ala Pro Arg Glu Gln Lys Lys Asn Leu675 680 685ACC TTT TAT CTA CTT CTT TCT CTA ATC CTG GTT TCT GTG GGC TTC GTG 2229Thr Phs Tyr Leu Leu Leu Ser Leu Ils Leu Val Ser Val Gly Phs Val690 695 700 705GTC ACA GTG TTC GGA GTA ATC ATA TTC AAA GTT TAC AAG TGG AAG CAG 2277Val Thr Val Phs Gly Val Ils Ils Phs Lys Val Tyr Lys Trp Lys Gln710 715 720TCT AGA GAC CTA TAC CGA GCC CCG GTG AGC TCA CTG TAC CGA ACA CCA 2325Ser Arg Asp Leu Tyr Arg Ala Pro Val Ser Ser Leu Tyr Arg Thr Pro725 730 735GGG CCC TCC TTG CAC GCG GAC GCC GTG CGG GGA GGC CTG ATG TCG CCG 2373Gly Pro Ser Leu His Ala Asp Ala Val Arg Gly Gly Leu Met Ser Pro740 745 750CAC CTT TAC CAT CAG GTG TAT CTC ACC ACG GAC TCC CGC CGC AGC GAC 2421His Leu Tyr His Gln Val Tyr Leu Thr Thr Asp Ser Arg Arg Ser Asp755 760 765CCG CTG CTG AAG AAA CCT GGT GCA GCC AGT CCA CTG GCC AGC CGC CAG 2469Pro Leu Leu Lys Lys Pro Gly Ala Ala Ser Pro Leu Ala Ser Arg Gln770 775 780 785AAC ACG CTG CGG AGC TGT GAT CCG GTG TTC TAT AGG CAG GTG TTG GGT 2517Asn Thr Leu Arg Ser Cys Asp Pro Val Phe Tyr Arg Gln Val Leu Gly790 795 800GCA GAG AGC GCC CCT CCC GGA CAG CAA GCC CCG CCC AAC ACG GAC TGG 2565Ala Glu Ser Ala Pro Pro Gly Gln Gln Ala Pro Pro Asn Thr Asp Trp805 810 815CGT TTC TCT CAG GCC CAG AGA CCC GGC ACC AGC GGC TCC CAA AAT GGC 2613Arg Phe Ser Gln Ala Gln Arg Pro Gly Thr Ser Gly Ser Gln Asn Gly820 825 830GAT GAC ACC GGC ACC TGG CCC AAC AAC CAG TTT GAC ACA GAG ATG CTG 2661Asp Asp Thr Gly Thr Trp Pro Asn Asn Gln Phe Asp Thr Glu Met Leu835 840 845CAA GCC ATG ATC TTG GCG TCC GCC AGT GAA GCT GCT GAT GGG AGC TCC 2709Gln Ala Met Ile Leu Ala Ser Ala Ser Glu Ala Ala Asp Gly Ser Ser850 855 860 865ACC CTG GGA GGG GGT GCC GGC ACC ATG GGA TTG AGC GCC CGC TAC GGA 2757Thr Leu Gly Gly Gly Ala Gly Thr Met Gly Leu Ser Ala Arg Tyr Gly870 875 880CCC CAG TTC ACC CTG CAG CAC GTG CCC GAC TAC CGC CAG AAT GTC TAC 2805Pro Gln Phe Thr Leu Gln His Val Pro Asp Tyr Arg Gln Asn Val Tyr885 890 895ATC CCA GGC AGC AAT GCA CAC T GACCAACGCA GCTGGCAAGC GGATGGCAAG2857Ile Pro Gly Ser Asn Ala His900GCCCAGCAGG TGGCAATGGC AACAAGAAGA AGTCGGCAAG AAGGAGAAGA AGTAACATGG 2917AGGCCAGGCC AAGAGCCACA GGGCAGCCTC TCCCCGAACC AGCCCAGCTT CTCCTTACCT 2977GCACCCAGGC CTCAGAGTTT CAGGGCTAAC CCCCAGAATA CTGGTAGGGG CCAAGGCATC 3037TCCCTTGGAA ACAGAAACAA GTGCCATCAC ACCATCCCTT CCCCAGGTGT AATATCCAAA 3097GCAGTTCCGC TGGGAACCCC ATCCAATCAG TGGCTGTACC CATTTGGGTA GTGGGGTTCA 3157TGTAGACACC AAGAACCATT TGCCACACCC CGTTTAGTTA CAGCTGAACC CTCCATCTTC 3217CAAATCAATC AGGCCCATCC ATCCCATGCC TCCCTCCTCC CCACCCCACT CCAACAGTTC 3277CTCTTTCCCG AGTAAGGTGG TTGGGGTGTT GAAGTACCAA GTAACCTACA AGCCTCCTAG 3337TTCTGAAAAG TTGGAAGGGC ATCATGACCT CTTGGCCTCT CCTTTGATTC TCAATCTTCC 3397CCCAAAGCAT GGTTTGGTGC CAGCCCCTTC ACCTCCTTCC AGAGCCCAAG ATCAATGCTC 3457AAGTTTTGGA GGACATGATC ACCATCCCCA TGGTACTGAT GCTTGCTGGA TTTAGGGAGG 3517GCATTTTGCT ACCAAGCCTC TTCCCAACGC CCTGGGACCA GTCTTCTGTT TTGTTTTTCA 3577TTGTTTGAGC TTTCCACTGC ATGCCTTGAC TTCCCCCACC TCCTCCTCAA ACAAGAGACT 3637CCACTGCATG TTCCAAGACA GTATGGGGTG GTAAGATAAG GAAGGGAAGT GTGTGGATGT 3697GGATGGTGGG GGCATGGACA AAGCTTGACA CATCAAGTTA TCAAGGCCTT GGAGGAGGCT 3757CTGTATGTCC TCAGGGGACT GACAACATCC TCCAGATTCC AGCCATAAAC CAATAACTAG 3817GCTGGACCCT TCCCACTACA TAATAGGGCT CAGCCAGGCA GCCAGCTTTG GGCTGAGCTA 3877ACAGGACCAA TGGATTAACT GGCATTTCAG TCCAAGGAAG CTCGAAGCAG GTTTAGGACC 3937AGGTCCCCTT GAGAGGTCAG AGGGGCCTCT GTGGGTGCTG GGTACTCCAG AGGTGCCACT 3997GGTGGAAGGG TCAGCGGAGC CCCAGCAGGA AGGGTGGGCC AGCCAGGCCA TTCTTAGTCC 4057CTGGGTTGGG GAGGCAGGGA GCTAGGGCAG GGACCAAATG AACAGAAAGT CTCAGCCCAG 4117GATGGGGCTT CTTCAACAGG CCCCTGCCCT CCTGAAGCCT CAGTCCTTCA CCTTGCCAGG 4177TGCCGTTTCT CTTCCGTGAA GGCCACTGCC CAGGTCCCCA GTGCGCCCCC TAGTGGCCAT 4237AGCCTGGTTA AAGTTCCCCA GTGCCTCCTT GTGATAGACC TTCTTCTCCC ACCCCCTTCT 4297GCCCCTGGGT CCCCGGCCAT CCAGCGGGGC TGCCAGAGAA CCCCAGACCT GCCCTTACAG 4357TAGTGTAGCG CCCCCTCCCT CTTTCGGCTG GTGTAGAATA GCCAGTAGTG TAGTGCGGTG 4417TGCTTTTACG TGATGGCGGG TGGGCAGCGG GCGGCGGCGT CCGCGCAGCC GTCTGTCCTT 4477GATCTGCCCG CGGCGGCCCG TGTTGTGTTT TGTGCTGTGT CCAGCGCTAA GGCGACCCCC 4537TCCCCCGTAC TGACTTCTCC TATAAGCGCT TCTCTTCGCA TAGTCACGTA GCTCCCACCC 4597CACCCTCTTC CTGTGTCTCA CGCAAGTTTT ATACTCTAAT ATTTATATGG CTTTTTTTCT 4657TCGACAAAAA AATAATAAAA CGTTTCTTCT GAAAAAAAAA AAAAAAAA 4705(2)SEQ ID NO97的信息(i)序列特征(A)長(zhǎng)度904氨基酸(B)類型氨基酸(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO97Met Val Pro Glu Ala Trp Arg Ser Gly Leu Val Ser Thr Gly Arg Val1 5 10 15Val Gly Val Leu Leu Leu Leu Gly Ala Leu Asn Lys Ala Ser Thr Val20 25 30Ile His Tyr Glu Ile Pro Glu Glu Arg Glu Lys Gly Phe Ala Val Gly35 40 45Asn Val Val Ala Asn Leu Gly Leu Asp Leu Gly Ser Leu Ser Ala Arg50 55 60
Arg Phe Pro Val Val Ser Gly Ala Ser Arg Arg Phe Phe Glu Val Asn65 70 75 80Arg Glu Thr Gly Glu Met Phe Vai Asn Asp Arg Leu Asp Arg Glu Glu85 90 95Leu Cys Gly Thr Leu Pro Ser Cys Thr Val Thr Leu Glu Leu Val Val100 105 110Glu Asn Pro Leu Glu Leu Phe Ser Val Glu Val Val Ile Gln Asp Ile115 120 125Asn Asp Asn Asn Pro Ala Phe Pro Thr Gln Glu Met Lys Leu Glu Ile130 135 140Ser Glu Ala Val Ala Pro Gly Thr Arg Phe Pro Leu Glu Ser Ala His145 150 155 160Aap Pro Asp Leu Gly Ser Asn Ser Leu Gln Thr Tyr Glu Leu Ser Arg165 170 175Asn Glu Tyr Phe Ala Leu Arg Val Gln Thr Arg Glu Asp Ser Thr Lys180 185 190Tyr Ala Glu Leu Val Leu Glu Arg Ala Leu Asp Arg Glu Arg Glu Prol95 200 205Ser Leu Gln Leu Val Leu Thr Ala Leu Asp Gly Gly Thr Pro Ala Leu210 215 220Ser Ala Ser Leu Pro Ile His Ile Lys Val Leu Asp Ala Asn Asp Asn225 230 235 240Ala Pro Val Phe Asn Gln Ser Leu Tyr Arg Ala Arg Val Pro Gly Gly245 250 255Cys Thr Ser Gly Thr Arg Val Val Gln Val Leu Ala Thr Asp Leu Asp260 265 270Glu Gly Pro Asn Gly Glu Ile Ile Tyr Ser Phe Gly Ser His Asn Arg275 280 285Ala Gly Val Arg Gln Leu Phe Ala Leu Asp Leu Val Thr Gly Met Leu290 295 300Thr Ile Lys Gly Arg Leu Asp Phe Glu Asp Thr Lys Leu His Glu Ile305 310 315 320Tyr Ile Gln Ala Lys Asp Lys Gly Ala Asn Pro Glu Gly Ala His Cys325 330 335Lys Val Leu Val Glu Val Val Asp Val Asn Asp Asn Ala Pro Glu Ile340 345 350Thr Val Thr Ser Val Tyr Ser Pro Val Pro Glu Asp Ala Ser Gly Thr355 360 365Val Ile Ala Leu Leu Ser Val Thr Asp Leu Asp Ala Gly Glu Asn Gly370 375 380
Leu Val Thr Cys Glu Val Pro Pro Gly Leu Pro Phe Ser Leu Thr Ser385 390 395 400Ser Leu Lys Asn Tyr Phe Thr Leu Lys Thr Ser Ala Asp Leu Asp Arg405 410 415Glu Thr val Pro Glu Tyr Asn Leu Ser Ile Thr Ala Arg Asp Ala Gly420 425 430Thr Pro Ser Leu Ser Ala Leu Thr Ile Val Arg Val Gln Val Ser Asp435 440 445Ile Asn Asp Asn Pro Pro Gln Ser Ser Gln Ser Ser Tyr Asp Val Tyr450 455 460Ile Glu Glu Asn Asn Leu Pro Gly Ala Pro Ile Leu Asn Leu Ser Val465 470 475 480Trp Asp Pro Asp Ala Pro Gln Asn Ala Arg Leu Ser Phe Phe Leu Leu485 490 495Glu Gln Gly Ala Glu Thr Gly Leu Val Gly Arg Tyr Phe Thr Ile Asn500 505 510Arg Asp Asn Gly Ile Val Ser Ser Leu Val Pro Leu Asp Tyr Glu Asp515 520 525Arg Arg Glu Phe Glu Leu Thr Ala His Ile Ser Asp Gly Gly Thr Pro530 535 540Val Leu Ala Thr Asn Ile Ser Val Asn Ile Phe Val Thr Asp Arg Asn545 550 555 560Asp Asn Ala Pro Gln Val Leu Tyr Pro Arg Pro Gly Gly Ser Ser Val565 570 575Glu Met Leu Pro Arg Gly Thr Ser Ala Gly His Leu Val Ser Arg Val580 585 590Val Gly Trp Asp Ala Asp Ala Gly His Asn Ala Trp Leu Ser Tyr Ser595 600 605Leu Phe Gly Ser Pro Asn Gln Ser Leu Phe Ala Ile Gly Leu His Thr610 615 620Gly Gln Ile Ser Thr Ala Arg Pro Val Gln Asp Thr Asp Ser Pro Arg625 630 635 640Gln Thr Leu Thr Val Leu Ile Lys Asp Asn Gly Glu Pro Ser Leu Ser645 650 655Thr Thr Ala Thr Leu Thr Val Ser Val Thr Glu Asp Ser Pro Glu Ala660 665 670Arg Ala Glu Phe Pro Ser Gly Ser Ala Pro Arg Glu Gln Lys Lys Asn675 680 685Leu Thr Phe Tyr Leu Leu Leu Ser Leu Ile Leu Val Ser Val Gly Phe690 695 700
Val Val Thr Val Phe Gly Val Ile Ile Phe Lys Val Tyr Lys Trp Lys705 710 715 720Gln Sar Arg Asp Leu Tyr Arg Ala Pro Val Ser Ser Leu Tyr Arg Thr725 730 735Pro Gly Pro Ser Leu His Ala Asp Ala Val Arg Gly Gly Leu Met Ser740 745 750Pro His Leu Tyr His Gln Val Tyr Leu Thr Thr Asp Ser Arg Arg Ser755 760 765Asp Pro Leu Leu Lys Lys Pro Gly Ala Ala Ser Pro Leu Ala Ser Arg770 775 780Gln Asn Thr Leu Arg Ser Cys Asp Pro Val Phe Tyr Arg Gln Val Leu785 790 795 800Gly Ala Glu Ser Ala Pro Pro Gly Gln Gln Ala Pro Pro Asn Thr Asp805 810 815Trp Arg Phe Ser Gln Ala Gln Arg Pro Gly Thr Ser Gly Ser Gln Asn820 825 830Gly Asp Asp Thr Gly Thr Trp Pro Asn Asn Gln Phe Asp Thr Glu Met835 840 845Leu Gln Ala Met Ile Leu Ala Ser Ala Ser Glu Ala Ala Asp Gly Ser850 855 860Ser Thr Leu Gly Gly Gly Ala Gly Thr Met Gly Leu Ser Ala Arg Tyr865 870 875 880Gly Pro Gln Phe Thr Leu Gln His Val Pro Asp Tyr Arg Gln Asn Val885 890 895Tyr Ile Pro Gly Ser Asn Ala His900(2)SEQ ID NO98的信息(i)序列特征(A)長(zhǎng)度441氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO98Asp Trp Val Ile Pro Pro Ile Asn Leu Pro Glu Asn Ser Arg Gly Pro1 5 10 15Phe Pro Gln Glu Leu Val Arg Ile Arg Ser Asp Arg Asp Lys Asn Leu20 25 30
Ser Leu Arg Tyr Thr Val Thr Gly Pro Gly Ala Asp Gln Pro Pro Thr35 40 45Gly Ile Phe Ile Ile Asn Pro Ile Ser Gly Gln Leu Ser Val Thr Lys50 55 60Pro Leu Asp Arg Glu Gln Ile Ala Arg Phe His Leu Arg Ala His Ala65 70 75 80Val Asp Ile Asn Gly Asn Gln Val Glu Asn Pro Ile Asp Ile Val Ile85 90 95Asn Val Ile Asp Met Asn Asp Asn Arg Pro Glu Phe Thr Ala Met Thr100 105 110Phe Tyr Gly Glu Val Pro Glu Asn Arg Val Asp Ile Ile Val Ala Asn115 120 125Leu Thr Val Thr Asp Lys Asp Gln Pro His Thr Pro Ala Trp Asn Ala130 135 140Val Thr Arg Ile Ser Gly Gly Asp Pro Thr Gly Arg Phe Ala Ile Gln145 150 155 160Thr Asp Pro Asn Ser Asn Asp Gly Leu Val Thr Val Val Lys Pro Ile165 170 175Asp Phe Glu Thr Asn Arg Met Phe Val Leu Thr Val Ala Ala Glu Asn180 185 190Gln Val Pro Leu Ala Lys Gly Ile Gln His Pro Pro Gln Ser Thr Ala195 200 205Thr Val Ser Val Thr Val Ile Asp Val Asn Glu Asn Pro Tyr Phe Ala210 215 220Pro Asn Pro Lys Ile Ile Arg Gln Glu Glu Gly Leu His Ala Gly Thr225 230 235 240Met Leu Thr Thr Phe Thr Ala Gly Asp Pro Asp Arg Tyr Met Gln Gln245 250 255Asn Ile Arg Tyr Thr Lys Leu Ser Asp Pro Ala Asn Trp Leu Lys Ile260 265 270Asp Pro Val Asn Gly Gln Ile Thr Thr Ile Ala Val Leu Asp Arg Glu275 280 285Ser Pro Ash Val Lys Ash Asn Ile Tyr Asn Ala Thr Phe Leu Ala Ser290 295 300Asp Asn Gly Ile Pro Pro Met Ser Gly Thr Gly Thr Leu Gln Ile Tyr305 310 315 320Leu Leu Asp Ile Asn Asp Asn Ala Pro Gln Val Leu Pro Gln Glu Ala325 330 335Glu Thr Cys Glu Thr Pro Asp Pro Asn Ser Ile Asn Ile Thr Thr Ala340 345 350
Leu Asp Tyr Asp Ile Asp Pro Asn Ala Gly Pro Phe Ala Tyr Asp Leu355 360 365Pro Leu Ser Pro Val Thr Ile Lya Arg Aan Trp Thr Ile Thr Arg Leu370 375 380Asn Gly Asp Phe Ala Gln Leu Asn Leu Lya Ile Lys Phe Leu Glu Ala385 390 395 400Gly Ile Tyr Glu Val Pro Ile Ile Ile Thr Asp Ser Gly Asn Pro Pro405 410 415Lys Ser Asn Lys Ser Ile Leu Arg Val Arg Val Cys Gln Cys Asp Phe420 425 430Asn Gly Asp Cys Thr Asp Val Asp Arg435 440(2)SEQ ID NO99的信息(i)序列特征(A)長(zhǎng)度105氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO99Glu Asp Thr Val Tyr Ser Phe Asp Ile Pro Glu Asn Ala Gln Arg Gly1 5 10 15Tyr Gln Val Gly Gln Ile Val Ala Arg Asp Ala Asp Leu Gly Gln Asn20 25 30Ala Gln Leu Ser Tyr Gly Val Val Ser Asp Trp Ala Asn Asp Val Phe35 40 45Ser Leu Asn Pro Gln Thr Gly Met Leu Thr Leu Thr Ala Arg Leu Asp50 55 60Tyr Glu Glu Val Gln His Tyr Ile Leu Ile Val Gln Ala Gln Asp Asn65 70 75 80Gly Gln Pro Ser Leu Ser Thr Thr Ile Thr Val Tyr Cys Asn Val Leu85 90 95Asp Leu Asn Asp Asn Ala Pro Ile Phe100 105(2)SEQ ID NO100的信息(i)序列特征(A)長(zhǎng)度7氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO100Asp Xaa Asp Xaa Gly Xaa Asn1 5(2)SEQ ID NO101的信息(i)序列特征(A)長(zhǎng)度7氨基酸(B)類型氨基酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO101Ala Xaa Asp Xaa Gly Xaa Pro1 5(2)SEQ ID NO102的信息(i)序列特征(A)長(zhǎng)度4650堿基對(duì)(B)類型核酸(C)鏈型單股
(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(ix)特征(A)名稱/鍵CDS(B)定位495..4103(xi)序列描述SEQ ID NO102CCTCTATTCG ACATTCTCTT TGGATTGTTT TGCTATAACT TGAAATTTGG GATGTCACAA 60ACGAAACTGT CATCTGTTTC CGCCAAACTG TGGTTCTGCT AATCTCCCAG GCTGGCAGCA 120TTGGAGACTT GCTGACTTCT TTCATCCCCC ACTCTTTTCA CCTGAAATTC CTTTCCTTGG 180TTTTGCTCTA AGTCCTATGC TTCAGTCAGG GGCCAACCAA ATCTCACTGC CTCCTTTTTA 240TCATGAAGCC TTTGATCACT GATAGTTCTT TTTATATCTT GAAAAATCAC CCTTCCCAGT 300ACAGTTAATA TTTAGTATCT CTACTCATCT TGGCACTTAC TCACAGCTCC ATAATTCAGT 360CGTTTTCGTA CCTCTTCATG GTGATGGGGA GCCCTTTGGA GGTGGTGACT GTGCTTTATA 420CTCCTCATGA TGCTTCACAT GTGGCAGGCG TGGAGTGCCC GGAGGCGGCC CTCCTGATTC 480TGGGGCCTCC CAGG ATG GAG CCC CTG AGG CAC AGC CCA GGC CCT GGG GGG530Met Glu Pro Leu Arg His Ser Pro Gly Pro Gly Gly1 5 10CAA CGG CTA CTG CTG CCC TCC ATG CTG CTA GCA CTG CTG CTC CTG CTG578Gln Arg Leu Leu Leu Pro Ser Met Leu Leu Ala Leu Leu Leu Leu Leu15 20 25GCT CCA TCC CCA GGC CAC GCC ACT CGG GTA GTG TAC AAG GTG CCG GAG626Ala Pro Ser Pro Gly His Ala Thr Arg Val Val Tyr Lys Val Pro Glu30 35 40GAA CAG CCA CCC AAC ACC CTC ATT GGG AGC CTC GCA GCC GAC TAT GGT674Glu Gln Pro Pro Asn Thr Leu Ile Gly Ser Leu Ala Ala Asp Tyr Gly45 50 55 60TTT CCA GAT GTG GGG CAC CTG TAC AAG CTA GAG GTG GGT GCC CCG TAC722Phe Pro Asp Val Gly His Leu Tyr Lys Leu Glu Val Gly Ala Pro Tyr65 70 75CTT CGC GTG GAT GGC AAG ACA GGT GAC ATT TTC ACC ACC GAG ACC TCC770Leu Arg Val Asp Gly Lys Thr Gly Asp Ile Phe Thr Thr Glu Thr Ser80 85 90ATC GAC CGT GAG GGG CTC CGT GAA TGC CAG AAC CAG CTC CCT GGT GAT818Ile Asp Arg Glu Gly Leu Arg Glu Cys Gln Asn Gln Leu Pro Gly Asp95 100 105CCC TGC ATC CTG GAG TTT GAG GTA TCT ATC ACA GAC CTC GTG CAG AAT866Pro Cys Ile Leu Glu Phe Glu Val Ser Ile Thr Asp Leu Val Gln Asn110 115 120GCG AGC CCC CGG CTG CTA GAG GGC CAG ATA GAA GTA CAA GAC ATC AAT 914Ala Ser Pro Arg Leu Leu Glu Gly Gln Ile Glu Val Gln Asp Ile Asn125 130 135 140GAC AAC ACA CCC AAC TTC GCC TCA CCA GTC ATC ACT CTG GCC ATC CCT 962Asp Asn Thr Pro Asn Phe Ala Ser Pro Val Ile Thr Leu Ala Ile Pro145 150 155GAG AAC ACC AAC ATC GGC TCA CTC TTC CCC ATC CCG CTG GCT TCA GAC 1010Glu Asn Thr Asn Ile Gly Ser Leu Phe Pro Ile Pro Leu Ala Ser Asp160 165 170CGT GAT GCT GGT CCC AAC GGT GTG GCA TCC TAT GAG CTG CAG GTG GCA 1058Arg Asp Ala Gly Pro Asn Gly Val Ala Ser Tyr Glu Leu Gln Val Ala175 180 185GAG GAC CAG GAG GAG AAG CAA CCA CAG CTC ATT GTG ATG GGC AAC CTG 1106Glu Asp Gln Glu Glu Lys Gln Pro Gln Leu Ile Val Met Gly Asn Leu190 195 200GAC CGT GAG CGC TGG GAC TCC TAT GAC CTC ACC ATC AAG GTG CAG GAT 1154Asp Arg Glu Arg Trp Asp Ser Tyr Asp Leu Thr Ile Lys Val Gln Asp205 210 215 220GGC GGC AGC CCC CCA CGC GCC ACG AGT GCC CTG CTG CGT GTC ACC GTG 1202Gly Gly Ser Pro Pro Arg Ala Thr Ser Ala Leu Leu Arg Val Thr Val225 230 235CTT GAC ACC AAT GAC AAC GCC CCC AAG TTT GAG CGG CCC TCC TAT GAG 1250Leu Asp Thr Asn Asp Asn Ala Pro Lys Phe Glu Arg Pro Ser Tyr Glu240 245 250GCC GAA CTA TCT GAG AAT AGC CCC ATA GGC CAC TCG GTC ATC CAG GTG 1298Ala Glu Leu Ser Glu Asn Ser Pro Ile Gly His Ser Val Ile Gln Val255 260 265AAG GCC AAT GAC TCA GAC CAA GGT GCC AAT GCA GAA ATC GAA TAC ACA 1346Lys Ala Asn Asp Ser Asp Gln Gly Ala Asn Ala Glu Ile Glu Tyr Thr270 275 280TTC CAC CAG GCG CCC GAA GTT GTG AGG CGT CTT CTT CGA CTG GAC AGG 1394Phe His Gln Ala Pro Glu Val Val Arg Arg Leu Leu Arg Leu Asp Arg285 290 295 300AAC ACT GGA CTT ATC ACT GTT CAG GGC CCG GTG GAC CGT GAG GAC CTA 1442Asn Thr Gly Leu Ile Thr Val Gln Gly Pro Val Asp Arg Glu Asp Leu305 310 315AGC ACC CTG CGC TTC TCA GTG CTT GCT AAG GAC CGA GGC ACC AAC CCC 1490Ser Thr Leu Arg Phe Ser Val Leu Ala Lys Asp Arg Gly Thr Asn Pro320 325 330AAG AGT GCC CGT GCC CAG GTG GTT GTG ACC GTG AAG GAC ATG AAT GAC 1538Lys Ser Ala Arg Ala Gln Val Val Val Thr Val Lye Asp Met Asn Asp335 340 345AAT GCC CCC ACC ATT GAG ATC CGG GGC ATA GGG CTA GTG ACT CAT CAA 1586Asn Ala Pro Thr Ile Glu Ile Arg Gly Ile Gly Leu Val Thr His Gln350 355 360GAT GGG ATG GCT AAC ATC TCA GAG GAT GTG GCA GAG GAG ACA GCT GTG1634Asp Gly Met Ala Asn Ile Ser Glu Asp Val Ala Glu Glu Thr Ala Val365 370 375 380GCC CTG GTG CAG GTG TCT GAC CGA GAT GAG GGA GAG AAT GCA GCT GTC1682Ala Leu Val Gln Val Ser Asp Arg Asp Glu Gly Glu Asn Ala Ala Val385 390 395ACC TGT GTG GTG GCA GGT GAT GTG CCC TTC CAG CTG CGC CAG GCC AGT1730Thr Cys Val Val Ala Gly Asp Val Pro Phe Gln Leu Arg Gln Ala Ser400 405 410GAG ACA GGC AGT GAC AGC AAG AAG AAG TAT TTC CTG CAG ACT ACC ACC1778Glu Thr Gly Ser Asp Ser Lys Lys Lys Tyr Phe Leu Gln Thr Thr Thr415 420 425CCG CTA GAC TAC GAG AAG GTC AAA GAC TAC ACC ATT GAG ATT GTG GCT1826Pro Leu Asp Tyr Glu Lys Val Lys Asp Tyr Thr Ile Glu Ile Val Ala430 435 440GTG GAC TCT GGC AAC CCC CCA CTC TCC AGC ACT AAC TCC CTC AAG GTG1874Val Asp Ser Gly Asn Pro Pro Leu Ser Ser Thr Asn Ser Leu Lys Val445 450 455 460CAG GTG GTG GAC GTC AAT GAC AAC GCA CCT GTC TTC ACT CAG AGT GTC1922Gln Val Val Asp Val Asn Asp Asn Ala Pro Val Phe Thr Gln Ser Val465 470 475ACT GAG GTC GCC TTC CCG GAA AAC AAC AAG CCT GGT GAA GTG ATT GCT1970Thr Glu Val Ala Phe Pro Glu Asn Asn Lys Pro Gly Glu Val Ile Ala480 485 490GAG ATC ACT GCC AGT GAT GCT GAC TCT GGC TCT AAT GCT GAG CTG GTT2018Glu Ile Thr Ala Ser Asp Ala Asp Ser Gly Ser Asn Ala Glu Leu Val495 500 505TAC TCT CTG GAG CCT GAG CCG GCT GCT AAG GGC CTC TTC ACC ATC TCA2066Tyr Ser Leu Glu Pro Glu Pro Ala Ala Lye Gly Leu Phe Thr Ile Ser510 515 520CCC GAG ACT GGA GAG ATC CAG GTG AAG ACA TCT CTG GAT CGG GAA CAG2114Pro Glu Thr Gly Glu Ile Gln Val Lys Thr Ser Leu Asp Arg Glu Gln525 530 535 540CGG GAG AGC TAT GAG TTG AAG GTG GTG GCA GCT GAC CGG GGC AGT CCT2162Arg Glu Ser Tyr Glu Leu Lys Val Val Ala Ala Asp Arg Gly Ser Pro545 550 555AGC CTC CAG GGC ACA GCC ACT GTC CTT GTC AAT GTG CTG GAC TGC AAT2210Ser Leu Gln Gly Thr Ala Thr Val Leu Val Asn Val Leu Asp Cys Asn560 565 570GAC AAT GAC CCC AAA TTT ATG CTG AGT GGC TAC AAC TTC TCA GTG ATG2258Asp Asn Asp Pro Lys Phe Met Leu Ser Gly Tyr Asn Phe Ser Val Met575 580 585GAG AAC ATG CCA GCA CTG AGT CCA GTG GGC ATG GTG ACT GTC ATT GAT2306Glu Aan Met Pro Ala Leu Ser Pro Val Gly Met Val Thr Val Ile Asp590 595 600GGA GAC AAG GGG GAG AAT GCC CAG GTG CAG CTC TCA GTG GAG CAG GAC 2354Gly Asp Lys Gly Glu Asn Ala Gln Val Gln Leu Ser Val Glu Gln Asp605 610 615 620AAC GGT GAC TTT GTT ATC CAG AAT GGC ACA GGC ACC ATC CTA TCC AGC 2402Asn Gly Asp Phe Val Ile Gln Asn Gly Thr Gly Thr Ile Leu Ser Ser625 630 635CTG AGC TTT GAT CGA GAG CAA CAA AGC ACC TAC ACC TTC CAG CTG AAG 2450Leu Ser Phe Asp Arg Glu Gln Gln Ser Thr Tyr Thr Phe Gln Leu Lys640 645 650GCA GTG GAT GGT GGC GTC CCA CCT CGC TCA GCT TAC GTT GGT GTC ACC 2498Ala Val Asp Gly Gly Val Pro Pro Arg Ser Ala Tyr Val Gly Val Thr655 660 665ATC AAT GTG CTG GAC GAG AAT GAC AAC GCA CCC TAT ATC ACT GCC CCT 2546Ile Asn Val Leu Asp Glu Asn Asp Asn Ala Pro Tyr Ile Thr Ala Pro670 675 680TCT AAC ACC TCT CAC AAG CTG CTG ACC CCC CAG ACA CGT CTT GGT GAG 2594Ser Aen Thr Ser His Lys Leu Leu Thr Pro Gln Thr Arg Leu Gly Glu685 690 695 700ACG GTC AGC CAG GTG GCA GCC GAG GAC TTT GAC TCT GGT GTC AAT GCC 2642Thr Val Ser Gln Val Ala Ala Glu Asp Phe Asp Ser Gly Val Asn Ala705 710 715GAG CTG ATC TAC AGC ATT GCA GGT GGC AAC CCT TAT GGA CTC TTC CAG 2690Glu Leu Ile Tyr Ser Ile Ala Gly Gly Asn Pro Tyr Gly Leu Phe Gln720 725 730ATT GGG TCA CAT TCA GGT GCC ATC ACC CTG GAG AAG GAG ATT GAG CGG 2738Ile Gly Ser His Ser Gly Ala Ile Thr Leu Glu Lys Glu Ile Glu Arg735 740 745CGC CAC CAT GGG CTA CAC CGC CTG GTG GTG AAG GTC AGT GAC CGC GGC 2786Arg His His Gly Leu His Arg Leu Val Val Lys Val Ser Asp Arg Gly750 755 760AAG CCC CCA CGC TAT GGC ACA GCC TTG GTC CAT CTT TAT GTC AAT GAG 2834Lys Pro Pro Arg Tyr Gly Thr Ala Leu Val His Leu Tyr Val Asn Glu765 770 775 780ACT CTG GCC AAC CGC ACG CTG CTG GAG ACC CTC CTG GGC CAC AGC CTG 2882Thr Leu Ala Asn Arg Thr Leu Leu Glu Thr Leu Leu Gly His Ser Leu785 790 795GAC ACG CCG CTG GAT ATT GAC ATT GCT GGG GAT CCA GAA TAT GAG CGC 2930Asp Thr Pro Leu Asp Ile Asp Ile Ala Gly Asp Pro Glu Tyr Glu Arg800 805 810TCC AAG CAG CGT GGC AAC ATT CTC TTT GGT GTG GTG GCT GGT GTG GTG 2978Ser Lys Gln Arg Gly Asn Ile Leu Phe Gly Val Val Ala Gly Val Val815 820 825GCC GTG GCC TTG CTC ATC GCC CTG GCG GTT CTT GTG CGC TAC TGC AGA 3026Ala Val Ala Leu Leu Ile Ala Leu Ala Val Leu Val Arg Tyr Cys Arg830 835 840CAG CGG GAG GCC AAA AGT GGT TAC CAG GCT GGT AAG AAG GAG ACC AAG 3074Gln Arg Glu Ala Lys Ser Gly Tyr Gln Ala Gly Lys Lys Glu Thr Lys845 850 855 860GAC CTG TAT GCC CCC AAG CCC AGT GGC AAG GCC TCC AAG GGA AAC AAA 3122Aap Leu Tyr Ala Pro Lys Pro Ser Gly Lys Ala Ser Lys Gly Asn Lys865 870 875AGC AAA GGC AAG AAG AGC AAG TCC CCA AAG CCC GTG AAG CCA GTG GAG 3170Ser Lys Gly Lys Lys Ser Lys Ser Pro Lys Pro Val Lys Pro Val Glu880 885 890GAC GAG GAT GAG GCC GGG CTG CAG AAG TCC CTC AAG TTC AAC CTG ATG 3218Asp Glu Asp Glu Ala Gly Leu Gln Lys Ser Leu Lys Phe Asn Leu Met895 900 905AGC GAT GCC CCT GGG GAC AGT CCC CGC ATC CAC CTG CCC CTC AAC TAC 3266Ser Asp Ala Pro Gly Asp Ser Pro Arg Ile His Leu Pro Leu Asn Tyr910 915 920CCA CCA GGC AGC CCT GAC CTG GGC CGC CAC TAT CGC TCT AAC TCC CCA 3314Pro Pro Gly Ser Pro Asp Leu Gly Arg His Tyr Arg Ser Asn Ser Pro925 930 935 940CTG CCT TCC ATC CAG CTG CAG CCC CAG TCA CCC TCA GCC TCC AAG AAG 3362Leu Pro Ser Ile Gln Leu Gln Pro Gln Ser Pro Ser Ala Ser Lys Lys945 950 955CAC CAG GTG GTA CAG GAC CTG CCA CCT GCA AAC ACA TTC GTG GGC ACC 3410His Gln Val Val Gln Asp Leu Pro Pro Ala Asn Thr Phe Val Gly Thr960 965 970GGG GAC ACC ACG TCC ACG GGC TCT GAG CAG TAC TCC GAC TAC AGC TAC 3458Gly Asp Thr Thr Ser Thr Gly Ser Glu Gln Tyr Ser Asp Tyr Ser Tyr975 980 985CGC ACC AAC CCC CCC AAA TAC CCC AGC AAG CAG TTA CCT CAC CGC CGC 3506Arg Thr Asn Pro Pro Lys Tyr Pro Ser Lys Gln Leu Pro His Arg Arg990 995 1000GTC ACC TTC TCG GCC ACC AGC CAG GCC CAG GAG CTG CAG GAC CCA TCC 3554Val Thr Phe Ser Ala Thr Ser Gln Ala Gln Glu Leu Gln Asp Pro Ser1005101010151020CAG CAC AGT TAC TAT GAC AGT GGC CTG GAG GAG TCT GAG ACG CCG TCC 3602Gln His Ser Tyr Tyr Asp Ser Gly Leu Glu Glu Ser Glu Thr Pro Ser102510301035AGC AAG TCA TCC TCA GGG CCT CGA CTC GGT CCC CTG GCC CTG CCT GAG 3650Ser Lys Ser Ser Ser Gly Pro Arg Leu Gly Pro Leu Ala Leu Pro Glu104010451050GAT CAC TAT GAG CGC ACC ACC CCT GAT GGC AGC ATA GGA GAG ATG GAG 3698Asp His Tyr Glu Arg Thr Thr Pro Asp Gly Ser Ile Gly Glu Met Glu105510601065CAC CCC GAG AAT GAC CTT CGC CCT TTG CCT GAT GTC GCC ATG ACA GGC 3746His Pro Glu Asn Asp Leu Arg Pro Leu Pro Asp Val Ala Met Thr Gly107010751080ACA TGT ACC CGG GAG TGC AGT GAG TTT GGC CAC TCT GAC ACA TGC TGG 3794Thr Cys Thr Arg Glu Cys Ser Glu Phe Gly His Ser Asp Thr Cys Trp1085109010951100ATG CCT GGC CAG TCA TCT CCC AGC CGC CGG ACC AAG AGC AGC GCC CTC 3842Mer Pro Gly Gln Ser Ser Pro Ser Arg Arg Thr Lys Ser Ser Ala Leu110511101115AAA CTC TCC ACC TTC ATG CCT TAC CAG GAC CGA GGA GGG CAG GAG CCT 3890Lys Leu Ser Thr Phe Met Pro Tyr Gln Asp Arg Gly Gly Gln Glu Pro112011251130GCG GGC GCC GGC AGC CCC AGC CCC CCG GAA GAC CGG AAC ACC AAA ACG 3938Ala Gly Ala Gly Ser Pro Ser Pro Pro Glu Asp Arg Asn Thr Lys Thr113511401145GCC CCC GTG CGC CTC CTG CCC TCC TAC AGT GCC TTC TCC CAC AGT AGC 3986Ala Pro Val Arg Leu Leu Pro Ser Tyr Ser Ala Phe Ser His Ser Ser115011551160CAT GAT TCC TGC AAG GAC TCG GCC ACC TTG GAG GAA ATC CCC CTG ACC 4034His Asp Ser Cys Lys Asp Ser Ala Thr Leu Glu Glu Ile Pro Leu Thr1165117011751180CAG ACC TCG GAC TTC CCA CCC GCA GCC ACA CCG GCA TCT GCC CAG ACG 4082Gln Thr Ser Asp Phe Pro Pro Ala Ala Thr Pro Ala Ser Ala Gln Thr118511901195GCC AAG CGC GAG ATC TAC CTG TGAGCCCCCT ACTGGCCGGC CCCCCTCCCC 4133AlaLys Arg Glu Ile Tyr Leu1200CAGCGCCGGC CAGCTCCCAA ATGCCCATTC CAGGGCCTCA CTCTCCACCC CTTCAGCGTG 4193GACTTCCTGC CAGGGCCCAA GTGGGGGTAT CACTGACCTC ATGACCACGC TGGCCCTTCT 4253CCCATGCAGG GTCCAGGTCC TCTCCCCTCA TTTCCATCTC CCAGCCCAGG GGCCCCTTCC 4313CCTTTATGGG GCTTCCCCCA GCTGATGCCC AAGAGGGCTC CTCTGCAATG ACTGGGCTCC 4373TTCCCTTGAC TTCCAGGGAG CACCCCCTCG ATTTGGGCAG ATGGTGGAGT CAAGGGTGGG 4433CAGCGTACTT CTAACTCATT GTTTCCCTCA TGGCCGACCA GGGCGGGGAT AGCATGCCCA 4493ATTTTAGCCC TGAAGCAGGG CTGAACTGGG GAGCCCCTTT CCCTGGGAGC TCCCAGAGGA 4553AACTCTTGAC CACCAGTGGC TCCCTGAAGG GCTTTTGTTA CCAAAGGTGG GGTAGGGACG 4613GGGGTGGGAG TGGAGCGGAG GCCTTGTTTT CCCGTGG 4650(2)SEQ ID NO103的信息(i)序列特征(A)長(zhǎng)度1203氨基酸
(B)類型氨基酸(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO103Met Glu Pro Leu Arg His Ser Pro Gly Pro Gly Gly Gln Arg Leu Leu1 5 10 15Leu Pro Ser Met Leu Leu Ala Leu Leu Leu Leu Leu Ala Pro Ser Pro20 25 30Gly His Ala Thr Arg Val Val Tyr Lys Val Pro Glu Glu Gln Pro Pro35 40 45Asn Thr Leu Ile Gly Ser Leu Ala Ala Asp Tyr Gly Phe Pro Asp Val50 55 60Gly His Leu Tyr Lys Leu Glu Val Gly Ala Pro Tyr Leu Arg Val Asp65 70 75 80Gly Lys Thr Gly Asp Ile Phe Thr Thr Glu Thr Ser Ile Asp Arg Glu85 90 95Gly Leu Arg Glu Cys Gln Asn Gln Leu Pro Gly Asp Pro Cys Ile Leu100 105 110Glu Phe Glu Val Ser Ile Thr Asp Leu Val Gln Asn Ala Ser Pro Arg115 120 125Leu Leu Glu Gly Gln Ile Glu Val Gln Asp Ile Asn Asp Asn Thr Pro130 135 140Asn Phe Ala Ser Pro Val Ile Thr Leu Ala Ile Pro Glu Asn Thr Asn145 150 155 160Ile Gly Ser Leu Phe Pro Ile Pro Leu Ala Ser Asp Arg Asp Ala Gly165 170 175Pro Asn Gly Val Ala Ser Tyr Glu Leu Gln Val Ala Glu Asp Gln Glu180 185 190Glu Lys Gln Pro Gln Leu Ile Val Met Gly Asn Leu Asp Arg Glu Arg195 200 205Trp Asp Ser Tyr Asp Leu Thr Ile Lys Val Gln Asp Gly Gly Ser Pro210 215220Pro Arg Ala Thr Ser Ala Leu Leu Arg Val Thr Val Leu Asp Thr Asn225 230 235 240Asp Asn Ala Pro Lys Phe Glu Arg Pro Ser Tyr Glu Ala Glu Leu Ser245 250 255Glu Asn Ser Pro Ile Gly Mis Ser Val Ile Gln Val Lys Ala Asn Asp260 265 270Ser Asp Gln Gly Ala Asn Ala Glu Ile Glu Tyr Thr Phe His Gln Ala275 280 285
Pro Glu Val Val Arg Arg Leu Leu Arg Leu Asp Arg Asn Thr Gly Leu290 295 300Ile Thr Val Gln Gly Pro Val Asp Arg Glu Asp Leu Ser Thr Leu Arg305 310 315 320Phe Ser Val Leu Ala Lys Asp Arg Gly Thr Asn Pro Lys Ser Ala Arg325 330 335Ala Gln Val Val Val Thr Val Lys Asp Met Asn Asp Asn Ala Pro Thr340 345 350Ile Glu Ile Arg Gly Ile Gly Leu Val Thr His Gln Asp Gly Met Ala355 360 365Aen Ile Ser Glu Asp Val Ala Glu Glu Thr Ala Val Ala Leu Val Gln370 375 380Val Ser Asp Arg Asp Glu Gly Glu Asn Ala Ala Val Thr Cys Val Val385 390 395 400Ala Gly Asp Val Pro Phe Gln Leu Arg Gln Ala Ser Glu Thr Gly Ser405 410 415Asp Ser Lys Lys Lys Tyr Phe Leu Gln Thr Thr Thr Pro Leu Asp Tyr420 425 430Glu Lys Val Lys Asp Tyr Thr Ile Glu Ile Val Ala Val Asp Ser Gly435 440 445Asn Pro Pro Leu Ser Ser Thr Asn Ser Leu Lys Val Gln Val Val Asp450 455 460Val Asn Asp Asn Ala Pro Val Phe Thr Gln Ser Val Thr Glu Val Ala465 470 475 480Phe Pro Glu Asn Asn Lys Pro Gly Glu Val Ile Ala Glu Ile Thr Ala485 490 495Ser Asp Ala Asp Ser Gly Ser Asn Ala Glu Leu Val Tyr Ser Leu Glu500 505 510Pro Glu Pro Ala Ala Lys Gly Leu Phe Thr Ile Ser Pro Glu Thr Gly515 520 525Glu Ile Gln Val Lys Thr Ser Leu Asp Arg Glu Gln Arg Glu Ser Tyr530 535 540Glu Leu Lys Val Val Ala Ala Asp Arg Gly Ser Pro Ser Leu Gln Gly545 550 555 560Thr Ala Thr Val Leu Val Asn val Leu Asp Cys Asn Asp Asn Asp Pro565 570 575Lys Phe Met Leu Ser Gly Tyr Asn Phe Ser Val Met Glu Asn Met Pro580 585 590Ala Leu Ser Pro Val Gly Met Val Thr Val Ile Asp Gly Asp Lys Gly595 600 605Glu Asn Ala Gln Val Gln Leu Ser Val Glu Gln Asp Asn Gly Asp Phe610 615 620
Val Ile Gln Asn Gly Thr Gly Thr Ile Leu Ser Ser Leu Ser Phe Asp625 630 635 640Arg Glu Gln Gln Ser Thr Tyr Thr Phe Gln Leu Lys Ala Val Asp Gly645 650 655Gly Val Pro Pro Arg Ser Ala Tyr Val Gly Val Thr Ile Asn Val Leu660 665 670Asp Glu Asn Asp Asn Ala Pro Tyr Ile Thr Ala Pro Ser Asn Thr Ser675 680 685His Lys Leu Leu Thr Pro Gln Thr Arg Leu Gly Glu Thr Val Ser Gln690 695 700Val Ala Ala Glu Asp Phe Asp Ser Gly Val Asn Ala Glu Leu Ile Tyr705 710 715 720Ser Ile Ala Gly Gly Asn Pro Tyr Gly Leu Phe Gln Ile Gly Ser His725 730 735Ser Gly Ala Ile Thr Leu Glu Lys Glu Ile Glu Arg Arg His His Gly740 745 750Leu His Arg Leu Val Val Lys Val Ser Asp Arg Gly Lys Pro Pro Arg755 760 765Tyr Gly Thr Ala Leu Val His Leu Tyr Val Asn Glu Thr Leu Ala Asn770 775 780Arg Thr Leu Leu Glu Thr Leu Leu Gly His Ser Leu Asp Thr Pro Leu785 790 795 800Asp Ile Asp Ile Ala Gly Asp Pro Glu Tyr Glu Arg Ser Lye Gln Arg805 810 815Gly Asn Ile Leu Phe Gly Val Val Ala Gly Val Val Ala Val Ala Leu820 825 830Leu Ile Ala Leu Ala Val Leu Val Arg Tyr Cys Arg Gln Arg Glu Ala835 840 845Lys Ser Gly Tyr Gln Ala Gly Lys Lys Glu Thr Lys Asp Leu Tyr Ala850 855 860Pro Lys Pro Ser Gly Lys Ala Ser Lys Gly Asn Lys Ser Lys Gly Lys865 870 875 880Lys Ser Lys Ser Pro Lys Pro Val Lys Pro Val Glu Asp Glu Asp Glu885 890 895Ala Gly Leu Gln Lys Ser Leu Lys Phe Asn Leu Met Ser Asp Ala Pro900 905 910Gly Asp Ser Pro Arg Ile His Leu Pro Leu Asn Tyr Pro Pro Gly Ser915 920 925Pro Asp Leu Gly Arg His Tyr Arg Ser Asn Ser Pro Leu Pro Ser Ile930 935 940Gln Leu Gln Pro Gln Ser Pro Ser Ala Ser Lys Lys His Gln Val Val945 950 955 960
Gln Asp Leu Pro Pro Ala Asn Thr Phe Val Gly Thr Gly Asp Thr Thr965 970 975Ser Thr Gly Ser Glu Gln Tyr Ser Asp Tyr Ser Tyr Arg Thr Ash Pro980 985 990Pro Lys Tyr Pro Ser Lys Gln Leu Pro His Arg Arg Val Thr Phe Ser995 10001005Ala Thr Ser Gln Ala Gln Glu Leu Gln Asp Pro Ser Gln His Ser Tyr101010151020Tyr Asp Ser Gly Leu Glu Glu Ser Glu Thr Pro Ser Ser Lys Ser Ser1025103010351040Ser Gly Pro Arg Leu Gly Pro Leu Ala Leu Pro Glu Asp His Tyr Glu104510501055Arg Thr Thr Pro Asp Gly Ser Ile Gly Glu Met Glu His Pro Glu Asn106010651070Asp Leu Arg Pro Leu Pro Asp Val Ala Met Thr Gly Thr Cys Thr Arg107510801085Glu Cys Ser Glu Phe Gly His Ser Asp Thr Cys Trp Met Pro Gly Gln109010951100Ser Ser Pro Ser Arg Arg Thr Lys Ser Ser Ala Leu Lys Leu Ser Thr1105111011151120Phe Met Pro Tyr Gln Asp Arg Gly Gly Gln Glu Pro Ala Gly Ala Gly112511301135Ser Pro Ser Pro Pro Glu Asp Arg Asn Thr Lys Thr Ala Pro Val Arg114011451150Leu Leu Pro Ser Tyr Ser Ala Phe Ser His Ser Ser His Aep Ser Cys115511601165Lys Asp Ser Ala Thr Leu Glu Glu Ile Pro Leu Thr Gln Thr Ser Asp117011751180Phe Pro Pro Ala Ala Thr Pro Ala Ser Ala Gln Thr Ala Lys Arg Glu1185119011951200Ile Tyr Leu(2)SEQ ID NO104的信息(i)序列特征(A)長(zhǎng)度2789堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型cDNA(ix)特征(A)名稱/鍵CDS(B)定位115..2622(xi)序列描述SEQ ID NO104CGAAAGCCAT GTCGGACTCG TCGCCCAGCG CCCAAGCGCT AACCCGCTGA AAGTTTCTCA 60GCGAAATCTC AGGGACGATC TGGACCCCGC TGAGAGGAAC TGCTTTTGAG TGAG ATG 117Met1GTC CCA GAG GCC TGG AGG AGC GGA CTG GTA AGC ACC GGG AGG GTA GTG 165Val Pro Glu Ala Trp Arg Ser Gly Leu Val Ser Thr Gly Arg Val Val5 10 15GGA GTT TTG CTT CTG CTT GGT GCC TTG AAC AAG GCT TCC ACG GTC ATT 213Gly Val Leu Leu Leu Leu Gly Ala Leu Asn Lys Ala Ser Thr Val Ile20 25 30CAC TAT GAG ATC CCG GAG GAA AGA GAG AAG GGT TTC GCT GTG GGC AAC 261His Tyr Glu Ile Pro Glu Glu Arg Glu Lys Gly Phe Ala Val Gly Asn35 40 45GTG GTC GCG AAC CTT GGT TTG GAT CTC GGT AGC CTC TCA GCC CGC AGG 309Val Val Ala Asn Leu Gly Leu Asp Leu Gly Ser Leu Ser Ala Arg Arg50 55 60 65TTC CCG GTG GTG TCT GGA GCT AGC CGA AGA TTC TTT GAG GTG AAC CGG 357Phe Pro Val Val Ser Gly Ala Ser Arg Arg Phe Phe Glu Val Asn Arg70 75 80GAG ACC GGA GAG ATG TTT GTG AAC GAC CGT CTG GAT CGA GAG GAG CTG 405Glu Thr Gly Glu Met Phe Val Asn Asp Arg Leu Asp Arg Glu Glu Leu85 90 95TGT GGG ACA CTG CCC TCT TGC ACT GTA ACT CTG GAG TTG GTA GTG GAG 453Cys Gly Thr Leu Pro Ser Cys Thr Val Thr Leu Glu Leu Val Val Glu100 105 110AAC CCG CTG GAG CTG TTC AGC GTG GAA GTG GTG ATC CAG GAC ATC AAC 501Asn Pro Leu Glu Leu Phe Ser Val Glu Val Val Ile Gln Asp Ile Asn115 120 125GAC AAC AAT CCT GCT TTC CCT ACC CAG GAA ATG AAA TTG GAG ATT AGC 549Asp Asn Asn Pro Ala Phe Pro Thr Gln Glu Met Lys Leu Glu Ile Ser130 135 140 145GAG GCC GTG GCT CCG GGG ACG CGC TTT CCG CTC GAG AGC GCG CAC GAT 597Glu Ala Val Ala Pro Gly Thr Arg Phe Pro Leu Glu Ser Ala His Aspl50 155 160CCC GAT CTG GGA AGC AAC TCT TTA CAA ACC TAT GAG CTG AGC CGA AAT 645Pro Asp Leu Gly Ser Asn Ser Leu Gln Thr Tyr Glu Leu Ser Arg Asn165 170 175GAA TAC TTT GCG CTT CGC GTG CAG ACG CGG GAG GAC AGC ACC AAG TAC 693Glu Tyr Phe Ala Leu Arg Val Gln Thr Arg Glu Asp Ser Thr Lys Tyr180 185 190GCG GAG CTG GTG TTG GAG CGC GCC CTG GAC CGA GAA CGG GAG CCT AGT 741Ala Glu Leu Val Leu Glu Arg Ala Leu Asp Arg Glu Arg Glu Pro Ser195 200 205CTC CAG TTA GTG CTG ACG GCG TTG GAC GGA GGG ACC CCA GCT CTC TCC 789Leu Gln Leu Val Leu Thr Ala Leu Asp Gly Gly Thr Pro Ala Leu Ser210 215 220 225GCC AGC CTG CCT ATT CAC ATC AAG GTG CTG GAC GCG AAT GAC AAT GCG 837Ala Ser Leu Pro Ile His Ile Lys Val Leu Asp Ala Asn Asp Asn Ala230 235 240CCT GTC TTC AAC CAG TCC TTG TAC CGG GCG CGC GTT CCT GGA GGA TGC 885Pro Val Phe Asn Gln Ser Leu Tyr Arg Ala Arg Val Pro Gly Gly Cys245 250 255ACC TCC GGC ACG CGC GTG GTA CAA GTC CTT GCA ACG GAT CTG GAT GAA 933Thr Ser Gly Thr Arg Val Val Gln Val Leu Ala Thr Asp Leu Asp Glu260 265 270GGC CCC AAC GGT GAA ATT ATT TAC TCC TTC GGC AGC CAC AAC CGC GCC 981Gly Pro Asn Gly Glu Ile Ile Tyr Ser Phe Gly Ser His Asn Arg Ala275 280 285GGC GTG CGG CAA CTA TTC GCC TTA GAC CTT GTA ACC GGG ATG CTG ACA1029Gly Val Arg Gln Leu Phe Ala Leu Asp Leu Val Thr Gly Met Leu Thr290 295 300 305ATC AAG GGT CGG CTG GAC TTC GAG GAC ACC AAA CTC CAT GAG ATT TAC1077Ile Lys Gly Arg Leu Asp Phe Glu Asp Thr Lys Leu His Glu Ile Tyr310 315 320ATC CAG GCC AAA GAC AAG GGC GCC AAT CCC GAA GGA GCA CAT TGC AAA1125IleGln Ala Lys Asp Lys Gly Ala Asn Pro Glu Gly Ala His Cys Lys325 330 335GTG TTG GTG GAG GTT GTG GAT GTG AAT GAC AAC GCC CCG GAG ATC ACA1173Val Leu Val Glu Val Val Asp Val Asn Asp Asn Ala Pro Glu Ile Thr340 345 350GTC ACC TCC GTG TAC AGC CCA GTA CCC GAG GAT GCC TCT GGG ACT GTC1221Val Thr Ser Val Tyr Ser Pro Val Pro Glu Asp Ala Ser Gly Thr Val355 360 365ATC GCT TTG CTC AGT GTG ACT GAC CTG GAT GCT GGC GAG AAC GGG CTG1269Ile Ala Leu Leu Ser Val Thr Asp Leu Asp Ala Gly Glu Asn Gly Leu370 375 380 385GTG ACC TGC GAA GTT CCA CCG GGT CTC CCT TTC AGC CTT ACT TCT TCC1317Val Thr Cys Glu Val Pro Pro Gly Leu Pro Phe Ser Leu Thr Ser Ser390 395 400CTC AAG AAT TAC TTC ACT TTG AAA ACC AGT GCA GAC CTG GAT CGG GAG1365Leu Lys Asn Tyr Phe Thr Leu Lys Thr Ser Ala Asp Leu Asp Arg Glu405 410 415ACT GTG CCA GAA TAC AAC CTC AGC ATC ACC GCC CGA GAC GCC GGA ACC 1413Thr Val Pro Glu Tyr Asn Leu Ser Ile Thr Ala Arg Asp Ala Gly Thr420 425 430CCT TCC CTC TCA GCC CTT ACA ATA GTG CGT GTT CAA GTG TCC GAC ATC 1461Pro Ser Leu Ser Ala Leu Thr Ile Val Arg Val Gln Val Ser Asp Ile435 440 445AAT GAC AAC CCT CCA CAA TCT TCT CAA TCT TCC TAC GAC GTT TAC ATT 1509Asn Asp Asn Pro Pro Gln Ser Ser Gln Ser Ser Tyr Asp Val Tyr Ile450 455 460 465GAA GAA AAC AAC CTC CCC GGG GCT CCA ATA CTA AAC CTA AGT GTC TGG 1557Glu Glu Asn Asn Leu Pro Gly Ala Pro Ile Leu Asn Leu Ser Val Trp470 475 480GAC CCC GAC GCC CCG CAG AAT GCT CGG CTT TCT TTC TTT CTC TTG GAG 1605Asp Pro Asp Ala Pro Gln Asn Ala Arg Leu Ser Phe Phe Leu Leu Glu485 490 495CAA GGA GCT GAA ACC GGG CTA GTG GGT CGC TAT TTC ACA ATA AAT CGT 1653Gln Gly Ala Glu Thr Gly Leu Val Gly Arg Tyr Phe Thr Ile Asn Arg500 505 510GAC AAT GGC ATA GTG TCA TCC TTA GTG CCC CTA GAC TAT GAG GAT CGG 1701Asp Asn Gly Ile Val Ser Ser Leu Val Pro Leu Asp Tyr Glu Asp Arg515 520 525CGG GAA TTT GAA TTA ACA GCT CAT ATC AGC GAT GGG GGC ACC CCG GTC 1749Arg Glu Phe Glu Leu Thr Ala His Ile Ser Asp Gly Gly Thr Pro Val530 535 540 545CTA GCC ACC AAC ATC AGC GTG AAC ATA TTT GTC ACT GAT CGC AAT GAC 1797Leu Ala Thr Asn Ile Ser Val Asn Ile Phe Val Thr Asp Arg Asn Asp550 555 560AAT GCC CCC CAG GTC CTA TAT CCT CGG CCA GGT GGG AGC TCG GTG GAG 1845Asn Ala Pro Gln Val Leu Tyr Pro Arg Pro Gly Gly Ser Ser Val Glu565 S70 575ATG CTG CCT CGA GGT ACC TCA GCT GGC CAC CTA GTG TCA CGG GTG GTA 1893Met Leu Pro Arg Gly Thr Ser Ala Gly His Leu Val Ser Arg Val Val580 585 590GGC TGG GAC GCG GAT GCA GGG CAC AAT GCC TGG CTC TCC TAC AGT CTC 1941Gly Trp Asp Ala Asp Ala Gly His Asn Ala Trp Leu Ser Tyr Ser Leu595 600 605TTT GGA TCC CCT AAC CAG AGC CTT TTT GCC ATA GGG CTG CAC ACT GGT 1989Phe Gly Ser Pro Asn Gln Ser Leu Phe Ala Ile Gly Leu His Thr Gly610 615 620 625CAA ATC AGT ACT GCC CGT CCA GTC CAA GAC ACA GAT TCA CCC AGG CAG 2037Gln Ile Ser Thr Ala Arg Pro Val Gln Asp Thr Asp Ser Pro Arg Gln630 635 640ACT CTC ACT GTC TTG ATC AAA GAC AAT GGG GAG CCT TCG CTC TCC ACC 2085Thr Leu Thr Val Leu Ile Lye Asp Asn Gly Glu Pro Ser Leu Ser Thr645 650 655ACT GCT ACC CTC ACT GTG TCA GTA ACC GAG GAC TCT CCT GAA GCC CGA2133Thr Ala Thr Leu Thr Val Ser Val Thr Glu Asp Ser Pro Glu Ala Arg660 665 670GCC GAG TTC CCC TCT GGC TCT GCC CCC CGG GAG CAG AAA AAA AAT CTC2181Ala Glu Phe Pro Ser Gly Ser Ala Pro Arg Glu Gln Lye Lye Asn Leu675 680 685ACC TTT TAT CTA CTT CTT TCT CTA ATC CTG GTT TCT GTG GGC TTC GTG2229Thr Phe Tyr Leu Leu Leu Ser Leu Ile Leu Val Ser Val Gly Phe Val690 695 700 705GTC ACA GTG TTC GGA GTA ATC ATA TTC AAA GTT TAC AAG TGG AAG CAG2277Val Thr Val Phe Gly Val Ile Ile Phe Lys Val Tyr Lys Trp Lys Gln710 715 720TCT AGA GAC CTA TAC CGA GCC CCG GTG AGC TCA CTG TAC CGA ACA CCA2325Ser Arg Asp Leu Tyr Arg Ala Pro Val Ser Ser Leu Tyr Arg Thr Pro725 730 735GGG CCC TCC TTG CAC GCG GAC GCC GTG CGG GGA GGC CTG ATG TCG CCG2373Gly Pro Ser Leu His Ala Asp Ala Val Arg Gly Gly Leu Met Ser Pro740 745 750CAC CTT TAC CAT CAG GTG TAT CTC ACC ACG GAC TCC CGC CGC AGC GAC2421His Leu Tyr His Gln Val Tyr Leu Thr Thr Asp Ser Arg Arg Ser Asp755 760 765CCG CTG CTG AAG AAA CCT GGT GCA GCC AGT CCA CTG GCC AGC CGC CAG2469Pro Leu Leu Lys Lys Pro Gly Ala Ala Ser Pro Leu Ala Ser Arg Gln770 775 780 785AAC ACG CTG CGG AGC TGT GAT CCG GTG TTC TAT AGG CAG GTG TTG GGT2517Asn Thr Leu Arg Ser Cys Asp Pro Val Phe Tyr Arg Gln Val Leu Gly790 795 800GCA GAG AGC GCC CCT CCC GGA CAG GTA AGG TTT AGC AAG TCA TGC TTG2565Ala Glu Ser Ala Pro Pro Gly Gln Val Arg Phe Ser Lys Ser Cys Leu805 810 815ACC CTG TTA GTG CCT TTT TAT TCC TAC ATC ATA TTG AGA AGG CTG GAG2613Thr Leu Leu Val Pro Phe Tyr Ser Tyr Ile Ile Leu Arg Arg Leu Glu820 825 830CTG TTT TTT TAGTGATGAA GATGTTTTCC TGGTGATGCA TTCACACTTT2662Leu Phe Phe835CAACTGGCTC TTCCTAGATC AAAGTTAGTG CCTTTGTGAG ATGGTGGCCT GCCAGAGTGT 2722GGTTTGTGGT CCCATTTCAG GGGGAAGATA CTTGACTCAT CTGTGGACCT AATTCACATC 2782CTCAGCG2789(2)SEQ ID NO105的信息(i)序列特征(A)長(zhǎng)度836氨基酸
(B)類型氨基酸(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO105Met Val Pro Glu Ala Trp Arg Ser Gly Leu Val Ser Thr Gly Arg Val1 5 10 15Val Gly Val Leu Leu Leu Leu Gly Ala Leu Asn Lys Ala Ser Thr Val20 25 30Ile His Tyr Glu Ile Pro Glu Glu Arg Glu Lys Gly Phe Ala Val Gly35 40 45Asn Val Val Ala Asn Leu Gly Leu Asp Leu Gly Ser Leu Ser Ala Arg50 55 60Arg Phe Pro Val Val Ser Gly Ala Ser Arg Arg Phe Phe Glu Val Asn65 70 75 80Arg Glu Thr Gly Glu Met Phe Val Asn Asp Arg Leu Asp Arg Glu Glu85 90 95Leu Cys Gly Thr Leu Pro Ser Cys Thr Val Thr Leu Glu Leu Val Val100 105 110Glu Asn Pro Leu Glu Leu Phe Ser Val Glu Val Val Ile Gln Asp Ile115 120 125Asn Asp Asn Asn Pro Ala Phe Pro Thr Gln Glu Met Lys Leu Glu Ile130 135 140Ser Glu Ala Val Ala Pro Gly Thr Arg Phe Pro Leu Glu Ser Ala His145 150 155 160Asp Pro Asp Leu Gly Ser Asn Ser Leu Gln Thr Tyr Glu Leu Ser Arg165 170 175Asn Glu Tyr Phe Ala Leu Arg Val Gln Thr Arg Glu Asp Ser Thr Lys180 185 190Tyr Ala Glu Leu Val Leu Glu Arg Ala Leu Asp Arg Glu Arg Glu Pro195 200 205Ser Leu Gln Leu Val Leu Thr Ala Leu Asp Gly Gly Thr Pro Ala Leu210 215 220Ser Ala Ser Leu Pro Ile His Ile Lys Val Leu Asp Ala Asn Asp Asn225 230 235 240Ala Pro Val Phe Asn Gln Ser Leu Tyr Arg Ala Arg Val Pro Gly Gly245 250 255Cys Thr Ser Gly Thr Arg Val Val Gln Val Leu Ala Thr Asp Leu Asp260 265 270Glu Gly Pro Asn Gly Glu Ile Ile Tyr Ser Phe Gly Ser His Asn Arg275 280 285
Ala Gly Val Arg Gln Leu Phe Ala Leu Asp Leu Val Thr Gly Met Leu290 295 300Thr Ile Lys Gly Arg Leu Asp Phe Glu Asp Thr Lys Leu His Glu Ile305 310 315 320Tyr Ile Gln Ala Lye Asp Lys Gly Ala Asn Pro Glu Gly Ala His Cys325 330 335Lys Val Leu Val Glu Val Val Asp Val Asn Asp Asn Ala Pro Glu Ile340 345 350Thr Val Thr Ser Val Tyr Ser Pro Val Pro Glu Asp Ala Ser Gly Thr355 360 365Val Ile Ala Leu Leu Ser Val Thr Asp Leu Asp Ala Gly Glu Asn Gly370 375 380Leu Val Thr Cys Glu Val Pro Pro Gly Leu Pro Phe Ser Leu Thr Ser385 390 395 400Ser Leu Lys Asn Tyr Phe Thr Leu Lys Thr Ser Ala Asp Leu Asp Arg405 410 415Glu Thr Val Pro Glu Tyr Asn Leu Ser Ile Thr Ala Arg Asp Ala Gly420 425 430Thr Pro Ser Leu Ser Ala Leu Thr Ile Val Arg Val Gln Val Ser Asp435 440 445Ile Asn Asp Asn Pro Pro Gln Ser Ser Gln Ser Ser Tyr Asp Val Tyr450 455 460Ile Glu Glu Asn Asn Leu Pro Gly Ala Pro Ile Leu Asn Leu Ser Val465 470 475 480Trp Asp Pro Asp Ala Pro Gln Asn Ala Arg Leu Ser Phe Phe Leu Leu485 490 495Glu Gln Gly Ala Glu Thr Gly Leu Val Gly Arg Tyr Phe Thr Ile Asn500 505 510Arg Asp Asn Gly Ile Val Ser Ser Leu Val Pro Leu Asp Tyr Glu Asp515 520 525Arg Arg Glu Phe Glu Leu Thr Ala His Ile Ser Asp Gly Gly Thr Pro530 535 540Val Leu Ala Thr Asn Ile Ser Val Asn Ile Phe Val Thr Asp Arg Asn545 550 555 560Asp Asn Ala Pro Gln Val Leu Tyr Pro Arg Pro Gly Gly Ser Ser Val565 570 575Glu Met Leu Pro Arg Gly Thr Ser Ala Gly His Leu Val Ser Arg Val580 585 590Val Gly Trp Asp Ala Asp Ala Gly His Asn Ala Trp Leu Ser Tyr Ser595 600 605Leu Phe Gly Ser Pro Asn Gln Ser Leu Phe Ala Ile Gly Leu His Thr610 615 620
Gly Gln Ile Ser Thr Ala Arg Pro Val Gln Asp Thr Asp Ser Pro Arg625 630 635 640Gln Thr Leu Thr Val Leu Ile Lys Asp Asn Gly Glu Pro Ser Leu Ser645 650 655Thr Thr Ala Thr Leu Thr Val Ser Val Thr Glu Asp Ser Pro Glu Ala660 665 670Arg Ala Glu Phe Pro Ser Gly Ser Ala Pro Arg Glu Gln Lys Lys Asn675 680 685Leu Thr Phe Tyr Leu Leu Leu Ser Leu Ile Leu Val Ser Val Gly Phe690 695 700Val Val Thr Val Phe Gly Val Ile Ile Phe Lys Val Tyr Lys Trp Lys705 710 715 720Gln Ser Arg Asp Leu Tyr Arg Ala Pro Val Ser Ser Leu Tyr Arg Thr725 730 735Pro Gly Pro Ser Leu His Ala Asp Ala Val Arg Gly Gly Leu Met Ser740 745 750Pro His Leu Tyr His Gln Val Tyr Leu Thr Thr Asp Ser Arg Arg Ser755 760 765Asp Pro Leu Leu Lys Lys Pro Gly Ala Ala Ser Pro Leu Ala Ser Arg770 775 780Gln Asn Thr Leu Arg Ser Cys Asp Pro Val Phe Tyr Arg Gln Val Leu785 790 795 800Gly Ala Glu Ser Ala Pro Pro Gly Gln Val Arg Phe Ser Lys Ser Cys805 810 815Leu Thr Leu Leu Val Pro Phe Tyr Ser Tyr Ile Ile Leu Arg Arg Leu820 825 830Glu Leu Phe Phe835(2)SEQ ID NO106的信息(i)序列特征(A)長(zhǎng)度2751堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(ix)特征(A)名稱/鍵CDS
(B)定位115..2160(xi)序列描述SEQ ID NO106CGAAAGCCAT GTCGGACTCG TCGCCCAGCG CCCAAGCGCT AACCCGCTGA AAGTTTCTCA 60GCGAAATCTC AGGGACGATC TGGACCCCGC TGAGAGGAAC TGCTTTTGAG TGAG ATG 117Met1GTC CCA GAG GCC TGG AGG AGC GGA CTG GTA AGC ACC GGG AGG GTA GTG 165Val Pro Glu Ala Trp Arg Ser Gly Leu Val Ser Thr Gly Arg Val Val5 10 15GGA GTT TTG CTT CTG CTT GGT GCC TTG AAC AAG GCT TCC ACG GTC ATT 213Gly Val Leu Leu Leu Leu Gly Ala Leu Asn Lys Ala Ser Thr Val Ile20 25 30CAC TAT GAG ATC CCG GAG GAA AGA GAG AAG GGT TTC GCT GTG GGC AAC 261His Tyr Glu Ile Pro Glu Glu Arg Glu Lys Gly Phe Ala Val Gly Asn35 40 45GTG GTC GCG AAC CTT GGT TTG GAT CTC GGT AGC CTC TCA GCC CGC AGG 309Val Val Ala Ash Leu Gly Leu Asp Leu Gly Ser Leu Ser Ala Arg Arg50 55 60 65TTC CCG GTG GTG TCT GGA GCT AGC CGA AGA TTC TTT GAG GTG AAC CGG 357Phe Pro Val Val Ser Gly Ala Ser Arg Arg Phe Phe Glu Val Asn Arg70 75 80GAG ACC GGA GAG ATG TTT GTG AAC GAC CGT CTG GAT CGA GAG GAG CTG 405Glu Thr Gly Glu Met Phe Val Asn Asp Arg Leu Asp Arg Glu Glu Leu85 90 95TGT GGG ACA CTG CCC TCT TGC ACT GTA ACT CTG GAG TTG GTA GTG GAG 453Cys Gly Thr Leu Pro Ser Cys Thr Val Thr Leu Glu Leu Val Val Glu100 105 110AAC CCG CTG GAG CTG TTC AGC GTG GAA GTG GTG ATC CAG GAC ATC AAC 501Asn Pro Leu Glu Leu Phe Ser Val Glu Val Val Ile Gln Asp Ile Asn115 120 125GAC AAC AAT CCT GCT TTC CCT ACC CAG GAA ATG AAA TTG GAG ATT AGC 549Asp Asn Asn Pro Ala Phe Pro Thr Gln Glu Met Lys Leu Glu Ile Ser130 135 140 145GAG GCC GTG GCT CCG GGG ACG CGC TTT CCG CTC GAG AGC GCG CAC GAT 597Glu Ala Val Ala Pro Gly Thr Arg Phe Pro Leu Glu Ser Ala His Asp150 155 160CCC GAT CTG GGA AGC AAC TCT TTA CAA ACC TAT GAG CTG AGC CGA AAT 645Pro Asp Leu Gly Ser Asn Ser Leu Gln Thr Tyr Glu Leu Ser Arg Asn165 170 175GAA TAC TTT GCG CTT CGC GTG CAG ACG CGG GAG GAC AGC ACC AAG TAC 693Glu Tyr Phe Ala Leu Arg Val Gln Thr Arg Glu Asp Ser Thr Lys Tyr180 185 190GCG GAG CTG GTG TTG GAG CGC GCC CTG GAC CGA GAA CGG GAG CCT AGT 741Ala Glu Leu Val Leu Glu Arg Ala Leu Asp Arg Glu Arg Glu Pro Ser195 200 205CTC CAG TTA GTG CTG ACG GCG TTG GAC GGA GGG ACC CCA GCT CTC TCC 789Leu Gln Leu Val Leu Thr Ala Leu Asp Gly Gly Thr Pro Ala Leu Ser210 215 220 225GCC AGC CTG CCT ATT CAC ATC AAG GTG CTG GAC GCG AAT GAC AAT GCG 837Ala Ser Leu Pro Ile His Ile Lys Val Leu Asp Ala Asn Asp Asn Ala230 235 240CCT GTC TTC AAC CAG TCC TTG TAC CGG GCG CGC GTT CCT GGA GGA TGC 885Pro Val Phe Asn Gln Ser Leu Tyr Arg Ala Arg Val Pro Gly Gly Cys245 250 255ACC TCC GGC ACG CGC GTG GTA CAA GTC CTT GCA ACG GAT CTG GAT GAA 933Thr Ser Gly Thr Arg Val Val Gln Val Leu Ala Thr Asp Leu Asp Glu260 265 270GGC CCC AAC GGT GAA ATT ATT TAC TCC TTC GGC AGC CAC AAC CGC GCC 981Gly Pro Asn Gly Glu Ile Ile Tyr Ser Phe Gly Ser His Asn Arg Ala275 280 285GGC GTG CGG CAA CTA TTC GCC TTA GAC CTT GTA ACC GGG ATG CTG ACA1029Gly Val Arg Gln Leu Phe Ala Leu Asp Leu Val Thr Gly Met Leu Thr290 295 300 305ATC AAG GGT CGG CTG GAC TTC GAG GAC ACC AAA CTC CAT GAG ATT TAC1077Ile Lys Gly Arg Leu Asp Phe Glu Asp Thr Lys Leu His Glu Ile Tyr310 315 320ATC CAG GCC AAA GAC AAG GGC GCC AAT CCC GAA GGA GCA CAT TGC AAA1125Ile Gln Ala Lys Asp Lys Gly Ala Asn Pro Glu Gly Ala His Cys Lys325 330 335GTG TTG GTG GAG GTT GTG GAT GTG AAT GAC AAC GCC CCG GAG ATC ACA1173Val Leu Val Glu Val Val Asp Val Asn Asp Asn Ala Pro Glu Ile Thr340 345 350GTC ACC TCC GTG TAC AGC CCA GTA CCC GAG GAT GCC TCT GGG ACT GTC1221Val Thr Ser Val Tyr Ser Pro Val Pro Glu Asp Ala Ser Gly Thr Val355 360 365ATC GCT TTG CTC AGT GTG ACT GAC CTG GAT GCT GGC GAG AAC GGG CTG1269Ile Ala Leu Leu Ser Val Thr Asp Leu Asp Ala Gly Glu Asn Gly Leu370 375 380 385GTG ACC TGC GAA GTT CCA CCG GGT CTC CCT TTC AGC CTT ACT TCT TCC1317Val Thr Cys Glu Val Pro Pro Gly Leu Pro Phe Ser Leu Thr Ser Ser390 395 400CTC AAG AAT TAC TTC ACT TTG AAA ACC AGT GCA GAC CTG GAT CGG GAG1365Leu Lys Asn Tyr Phe Thr Leu Lys Thr Ser Ala Asp Leu Asp Arg Glu405 410 415ACT GTG CCA GAA TAC AAC CTC AGC ATC ACC GCC CGA GAC GCC GGA ACC1413Thr Val Pro Glu Tyr Asn Leu Ser Ile Thr Ala Arg Asp Ala Gly Thr420 425 430CCT TCC CTC TCA GCC CTT ACA ATA GTG CGT GTT CAA GTG TCC GAC ATC1461Pro Ser Leu Ser Ala Leu Thr Ile Val Arg Val Gln Val Ser Asp Ile435 440 445AAT GAC AAC CCT CCA CAA TCT TCT CAA TCT TCC TAC GAC GTT TAC ATT 1509Asn Asp Asn Pro Pro Gln Ser Ser Gln Ser Ser Tyr Asp Val Tyr Ile450 455 460 465GAA GAA AAC AAC CTC CCC GGG GCT CCA ATA CTA AAC CTA AGT GTC TGG 1557Glu Glu Asn Asn Leu Pro Gly Ala Pro Ile Leu Asn Leu Ser Val Trp470 475 480GAC CCC GAC GCC CCG CAG AAT GCT CGG CTT TCT TTC TTT CTC TTG GAG 1605Asp Pro Asp Ala Pro Gln Asn Ala Arg Leu Ser Phe Phe Leu Leu Glu485 490 495CAA GGA GCT GAA ACC GGG CTA GTG GGT CGC TAT TTC ACA ATA AAT CGT 1653Gln Gly Ala Glu Thr Gly Leu Val Gly Arg Tyr Phe Thr Ile Asn Arg500 505 510GAC AAT GGC ATA GTG TCA TCC TTA GTG CCC CTA GAC TAT GAG GAT CGG 1701Asp Asn Gly Ile Val Ser Ser Leu Val Pro Leu Asp Tyr Glu Asp Arg515 520 525CGG GAA TTT GAA TTA ACA GCT CAT ATC AGC GAT GGG GGC ACC CCG GTC 1749Arg Glu Phe Glu Leu Thr Ala His Ile Ser Asp Gly Gly Thr Pro Val530 535 540 545CTA GCC ACC AAC ATC AGC GTG AAC ATA TTT GTC ACT GAT CGC AAT GAC 1797Leu Ala Thr Asn Ile Ser Val Asn Ile Phe Val Thr Asp Arg Asn Asp550 555 560AAT GCC CCC CAG GTC CTA TAT CCT CGG CCA GGT GGG AGC TCG GTG GAG 1845Asn Ala Pro Gln Val Leu Tyr Pro Arg Pro Gly Gly Ser Ser Val Glu565 570 575ATG CTG CCT CGA GGT ACC TCA GCT GGC CAC CTA GTG TCA CGG GTG GTA 1893Met Leu Pro Arg Gly Thr Ser Ala Gly His Leu Val Ser Arg Val Val580 585 590GGC TGG GAC GCG GAT GCA GGG CAC AAT GCC TGG CTC TCC TAC AGT CTC 1941Gly Trp Asp Ala Asp Ala Gly His Ash Ala Trp Leu Ser Tyr ser Leu595 600 605TTT GGA TCC CCT AAC CAG AGC CTT TTT GCC ATA GGG CTG CAC ACT GGT 1989Phe Gly Ser Pro Asn Gln Ser Leu Phe Ala Ile Gly Leu His Thr Gly610 615 620 625CAA ATC AGT ACT GCC CGT CCA GTC CAA GAC ACA GAT TCA CCC AGG CAG 2037Gln Ile Ser Thr Ala Arg Pro Val Gln Asp Thr Asp Ser Pro Arg Gln630 635 640ACT CTC ACT GTC TTG ATC AAA GAC AAT GGG GAG CCT TCG CTC TCC ACC 2085Thr Leu Thr Val Leu Ile Lys Asp Asn Gly Glu Pro Ser Leu Ser Thr645 650 655ACT GCT ACC CTC ACT GTG TCA GTA ACC GAG GAC TCT CCT GAA GCC CGA 2133Thr Ala Thr Leu Thr Val Ser Val Thr Glu Asp Ser Pro Glu Ala Arg660 665 670GCC GAG TTC CCC TCT GGC TCT GCC AGT TAAACCTTCT TTAATTATGG 2180Ala Glu Phe Pro Ser Gly Ser Ala Ser675 680ATTAGCCATT AACATTTTTG AAACGTGGAC CATTTAACCT CGGCCTACCC CCTCCAACTG 2240TCCTGGTGAT GAGTTCATTA GCTAAGTTAA ATTAATTGAA CTTTGATCTA AACCAAAACA 2300AATCAGGAAA ATAAAGCTGT AAAGGAACTT ATCAAGCATT CCAAAACCAA CTAGAAATTA 2360CTTGAAGTTT CGAGTGAGCA TTGCCTGTGC CAGTATTCTT CATTATAGGA TTATAAACTC 2420GTTTTTTTCC CAAAGCGCAT GTCTACGCCA GGCAGAGGAG TAATTATTCA GCCAATTTCA 2480TGGATGTAAC GATGGATATA AATAATTGAT AGCACCTAGA GGCTTCCAGT TTGGGTGGAA 2540GGCTAAAAGT AGAGGGGAAC TCACTCACTT GAGAAATGAT ATTTAAGTGA ATAAATAGTT 2600CTCTTCTATG AAACTATTAC TATTTAGTTC TCTGGAAAAC TTAAGTGTAT TAATGATTAG 2660AACATCAAAT CCTAAGTAAA GAAATGACAT TTTAAATATA AAAAGCCAAA CTTTAAATAA 2720ATCATAGAGA CCTCAGACAT AATATAGGAA A 2751(2)SEQ ID NO107的信息(i)序列特征(A)長(zhǎng)度682氨基酸(B)類型氨基酸(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO107Met Val Pro Glu Ala Trp Arg Ser Gly Leu Val Ser Thr Gly Arg Val1 5 10 15Val Gly Val Leu Leu Leu Leu Gly Ala Leu Asn Lys Ala Ser Thr Val20 25 30Ile His Tyr Glu Ile Pro Glu Glu Arg Glu Lys Gly Phe Ala Val Gly35 40 45Asn Val Val Ala Asn Leu Gly Leu Asp Leu Gly Ser Leu Ser Ala Arg50 55 60Arg Phe Pro Val Val Ser Gly Ala Ser Arg Arg Phe Phe Glu Val Asn65 70 75 80Arg Glu Thr Gly Glu Met Phe Val Asn Asp Arg Leu Asp Arg Glu Glu85 90 95Leu Cys Gly Thr Leu Pro Ser Cys Thr Val Thr Leu Glu Leu Val Val100 105 110Glu Asn Pro Leu Glu Leu Phe Ser Val Glu Val Val Ile Gln Asp Ile115 120 125Asn Asp Asn Asn Pro Ala Phe Pro Thr Gln Glu Met Lys Leu Glu Ile130 135 140Ser Glu Ala Val Ala Pro Gly Thr Arg Phe Pro Leu Glu Ser Ala His145 150 155 160Asp Pro Asp Leu Gly Ser Asn Ser Leu Gln Thr Tyr Glu Leu Ser Arg165 170 175Asn Glu Tyr Phe Ala Leu Arg Val Gln Thr Arg Glu Asp Ser Thr Lye180 185 190Tyr Ala Glu Leu Val Leu Glu Arg Ala Leu Asp Arg Glu Arg Glu Pro195 200 205Ser Leu Gln Leu Val Leu Thr Ala Leu Asp Gly Gly Thr Pro Ala Leu210 215 220Ser Ala Ser Leu Pro Ile His Ile Lys Val Leu Asp Ala Asn Asp Asn225 230 235 240Ala Pro Val Phe Asn Gln Ser Leu Tyr Arg Ala Arg Val Pro Gly Gly245 250 255Cys Thr Ser Gly Thr Arg Val Val Gln Val Leu Ala Thr Asp Leu Asp260 265 270Glu Gly Pro Asn Gly Glu Ile Ile Tyr Ser Phe Gly Ser His Asn Arg275 280 285Ala Gly Val Arg Gln Leu Phe Ala Leu Asp Leu Val Thr Gly Met Leu290 295 300Thr Ile Lys Gly Arg Leu Asp Phe Glu Asp Thr Lys Leu His Glu Ile305 310 315 320Tyr Ile Gln Ala Lys Asp Lys Gly Ala Asn Pro Glu Gly Ala His Cys325 330 335Lys Val Leu Val Glu Val Val Asp Val Asn Asp Asn Ala Pro Glu Ile340 345 350Thr Val Thr Ser Val Tyr Ser Pro Val Pro Glu Asp Ala Ser Gly Thr355 360 365Val Ile Ala Leu Leu Ser Val Thr Asp Leu Asp Ala Gly Glu Asn Gly370 375 380Leu Val Thr Cys Glu Val Pro Pro Gly Leu Pro Phe Ser Leu Thr Ser385 390 395 400Ser Leu Lys Asn Tyr Phe Thr Leu Lys Thr Ser Ala Asp Leu Asp Arg405 410 415Glu Thr Val Pro Glu Tyr Asn Leu Ser Ile Thr Ala Arg Asp Ala Gly420 425 430Thr Pro Ser Leu Ser Ala Leu Thr Ile Val Arg Val Gln Val Ser Asp435 440 445Ile Asn Asp Asn Pro Pro Gln Ser Ser Gln Ser Ser Tyr Asp Val Tyr450 455 460Ile Glu Glu Asn Asn Leu Pro Gly Ala Pro Ile Leu Asn Leu Ser Val465 470 475 480Trp Asp Pro Asp Ala Pro Gln Asn Ala Arg Leu Ser Phe Phe Leu Leu485 490 495Glu Gln Gly Ala Glu Thr Gly Leu Val Gly Arg Tyr Phe Thr Ile Asn500 505 510Arg Asp Asn Gly Ile Val Ser Ser Leu Val Pro Leu Asp Tyr Glu Asp515 520 525Arg Arg Glu Phe Glu Leu Thr Ala His Ile Ser Asp Gly Gly Thr Pro530 535 540Val Leu Ala Thr Asn Ile Ser Val Asn Ile Phe Val Thr Asp Arg Asn545 550 555 560Asp Asn Ala Pro Gln Val Leu Tyr Pro Arg Pro Gly Gly Ser Ser Val565 570 575Glu Met Leu Pro Arg Gly Thr Ser Ala Gly His Leu Val Ser Arg Val580 585 590Val Gly Trp Asp Ala Asp Ala Gly His Asn Ala Trp Leu Ser Tyr Ser595 600 605Leu Phe Gly Ser Pro Asn Gln Ser Leu Phe Ala Ile Gly Leu His Thr610 615 620Gly Gin Ile Ser Thr Ala Arg Pro Val Gln Asp Thr Asp Ser Pro Arg625 630 635 640Gln Thr Leu Thr Val Leu Ile Lys Asp Asn Gly Glu Pro Ser Leu Ser645 650 655Thr Thr Ala Thr Leu Thr Val Ser Val Thr Glu Asp Ser Pro Glu Ala660 665 670Arg Ala Glu Phe Pro Ser Gly Ser Ala Ser675 680(2)SEQ ID NO108的信息(i)序列特征(A)長(zhǎng)度2831堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性
(ii)分子類型cDNA(xi)序列描述SEQ ID NO108GAATTCGGCA CGAGGCTGAA CTGAGGGTGA CGGACATAAA CGACTATTCT CCAGTGTTCA60GTGAAAGAGA AATGATACTG AGGATACCAG AAAACAGTGC TCGGGGAAAT ACATTCCCTT 120TAAACAATGC TCTGGACTCA GACGTAGATA TCAACAATAT CCAGACCTAT AGGCTCAGCT 180CAAACTCTCA TTTCCTGGTT GTAACCCGCA ACCGCAGTGA TGGCAGGAAG TACCCAGAGC 240TGGTGCTGGA GAAAGAACTG GATCGAGAGG AGGAACCTGA GCTGAGGTTA ACGCTGACAG 300CTTTGGATGG TGGCTCTCCT CCCCGGTCTG GGACGACACA GGTCCTCATT GAAGTAGTGG 360ACACCAACGA TAATGCACCC GAGTTTCAGC AGCCAACATA CCAAGTGCAA ACTCCCGAGA 420ACAGTCCCAC CGGCTCTCTG GTACTCACAG TCTCAGCCAA TGACTTAGAC AGTGGAGACT 480ATGGGAAAGT CTTGTACGCA CTTTCGCAAC CCTCAGAAGA TATTAGCAAA ACATTCGAGG 540TAAACCCTGT AACCGGGGAA ATTCGCCTAC GAAAAGAGGT GAATTTTGAA ACTATTCCTT 600CGTATGAAGT GGTTATCAAG GGGACGGACG GGGGAGGTCT CTCAGGAAAA TGCACTCTGT 660TACTGCAGGT GGTGGACGTG AATGACAATG CCCCAGAAGT GATGCTATCT GCGCTAACCA 720ACCCAGTCCC AGAAAATTCC CCCGATGAGG TAGTGGCTGT TTTCAGTGTT AGAGATCCTG 780ACTCTGGGAA CAACGGAAAA GTGATTGCAT CCATCGAGGA AGACCTGCCC TTTCTTCTAA 840AATCTTCAGG AAAGAACTTT TACACTTTAG TAACCAAGGG AGCACTTGAC AGGGAAGAAA 900GAGAGCAATT GAACATCACC ATCACAGTCA CTGACCTGGG CATACCCAGG CTCACCACCC 960AACACACCAT AACAGTGCAG GTGGCAGACA TCAACGACAA TGCCCCCTCC TTCACCCAAA 1020CCTCCTACAC CATGTTTGTC CGCGAGAACA ACAGCCCCGC CCTGCACATA GGCACCATCA 1080GCGCCACAGA CTCAGACTCA GGATCCAATG CCCACATCAC CTACTCGCTG CTACCGCCCC 1140AAGACCCACA GCTGGCCCTC GACTCGCTCA TCTCCATCAA TGTAGACAAC GGGCAGCTGT 1200TCGCGCTCAG GGCGCTAGAC TATGAGGCTC TGCAGGGCTT CGAGTTCCAT GTGGGCGCCA 1260CAGACCAAGG CTCGCCCGCG CTCAGCAGCC AGGCTCTGGT GCACGTGGTG GTGTTGGACG 1320ACAATGACAA TGCGCCCTTC GTGCTCTACC CGCTGCAAAA CGCCTCTGCA CCCTTCACTG 1380AGCTGCTGCC CAGGGCGGCA GAGCCTGGAT ACCTGGTTAC CAAGGTGGTA GCTGTGGACC 1440GCGACTCTGG CCAGAATGCC TGGCTGTCAT TCCAGCTGCT CAAGGCCACG GAGCCCGGGC 1500TGTTCAACGT ATGGGCGCAC AATGGCGAGG TACGCACCTC CAGGCTGCTG AGCGAGCGCG 1560ACGCACCCAA GCACAAGCTG CTGCTGTTGG TCAAGGACAA TGGAGATCCT CCACGCTCTG 1620CCAGTGTTAC TCTGCACGTG CTAGTGGTGG ATGCCTTCTC TCAGCCCTAC CTGCCTCTGC 1680CAGAGGTGGC GCACGACCCT GCACAAGAAG AAGATGCGCT AACACTCTAC CTGGTCATAG 1740CTTTGGCATC TGTGTCTTCT CTCTTCCTCT TGTCTGTGCT GCTGTTCGTG GGGGTGAGGC 1800TCTGCAGGAG GGCCAGGGCA GCCTCTCTGA GTGCCTATTC TGTGCCTGAA GGCCACTTTC 1860CTGGCCAGCT GGTGGATGTC AGAGGTATGG GGACCCTGTC CCAGAGCTAC CAGTATGATG 1920TATGTCTGAT GGGGGATTCT TCTGGGACCA GCGAATTTAA CTTCTTAAAG CCAGTTCTGC 1980CTAGCTCTCT GCACCAGTGC TCTGGGAAAG AAATAGAGGA AAATTCCACA CTCCAGAATA 2040GTTTTGGGTT TCATCATTAA TAGAAAACTA CTTTACAGAT ATTTAATTCC AAATATCATC 2100TTGTTGATTA ACTAAAGTCT GTTCACATGT AGCTAGCTAG CAACGATTTT AATGTTCACT 2160TTACCCATCT TTTTTCAGGG TCATGTCTAA AGCTACAAGT TTGNCTTTAC TTATACTTGT 2220CGCACAGAAT NNNNNNNNNN TGGTGTATAA GTCACAGTCA TGGGATACTG GCACAAGATG 2280GCAGCTTGAT TGCTCAGTTA TGGCTGCAAA GGGGNGCTTG AGTTTAGGGA ATGTGTTAGA 2340GCTGGAATAA GTTTTCTGAG AAATGTGTAA GACAAATTTC TTTTGCACAT TCCCTGTGTT 2400CCTGTACCCC TGTTTCCAGA ACTACGAAAT GTGTCATCAG AAGGCATGCT CACATTTTCC 2460CCTTTGTTTG CGTGACCCGG GTGCCAGAAA TTAAATAAAA TTAGCATGGA GTTCAATGCA 2520GCATTAAAAC AAAGTTACTT CTACAAACCT TTTATTCGAC GGTTAAAATT GTAACTTCCC 2580CACCCATGAG GCTGGCTGTA AGAACCAGTA TGAATGGGTG TCTATCGCAA CCTTATTTTC 2640AAAAATCAAA CAAAAGGAGA AATGAGAGAC CAAACAACAC GCTACAGGAA AGATTTCATA 2700AGGATGTATG TATGGACACA AAAACTGGGA TACAGACATT TTAAATCTGT TGGTACCACA 2760TGGTGGCGCT GCAGGCTAAA GAAATGCAAG GGAAATTAAA AAGAGGCTGA GCTAGAAGTC 2820AAAAAAAAAA A 2831(2)SEQ ID NO109的信息(i)序列特征(A)長(zhǎng)度3353堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(ix)特征(A)名稱/鍵CDS(B)定位763..3123(xi)序列描述SEQ ID NO109GTATTTTTCC ACAGTTTAAA ATTTTCATAA AATCATAACT CTCTGACTTT ATGTAGAAAG60GATACCACAC TGGAATTAAC GTGTAGCTTT TTCTTGATGT AATCCAACCA ATGGGAGCAC 120AATTCTGGTA CATAGGCTGT CTAGAATTTG AAAGAAATTA AAGAATTCAT TTTGTTTTGC 180TGATAAATTT TTAAGAAATC ACGTGGCTTT ATGTTATTAT TATTACAAGA TGACTGATCA 240CTATTATGTC TTCTTTCACT TCTCAATTTC CCTCAGAACA CTACACCCAG ACTACAGGCT 300CTGGAGGGTG GGGACCATGT CTGGGTTGTT TACTGATGTA TTTCATAATT TGGCACATAG 360AGACCAATAA TACTCCTTTA AATGAAGAAA TTAATAATTA CCATTGCGTG ATATTGTGAT 420TACATCATTT CCTCCCAATT TCCAAACTCC TAATAGAATA GAGAATAGAT CAATTGTAGC 480AATTCGTTTC GAAGCAAAGA CAACGCATGG TGGCGCTGCA GGCTAAGGCT TCAAAAAAAG 540GAAAAGGAAA AAGCCCATGA AATGCTACTA GCTACTTCAG ACCTCTTTCA GCCTAAGAGG 600AAAGCCTGTT AGCAGAGCAC GGACCAGTGT CTCCGGAGAA TGCTATTCTC CTACATTTCC 660GAACAGGTTA TCAACGCACA GATCGATCAC TGCCTCTGTC CCATCGCTCC CTGAAGTAGC 720TCTGACTCCG GTTCCTTGAA AGGGGCGTGT ACAGAAGTAA AG ATG GAG CCT GCA 774Met Glu Pro Ala1GGG GAG CGC TTT CCC GAA CAA AGG CAA GTC CTG ATT CTC CTT CTT TTA 822Gly Glu Arg Phe Pro Glu Gln Arg Gln Val Leu Ile Leu Leu Leu Leu5 10 15 20CTG GAA GTG ACT CTG GCA GGC TGG GAA CCC CGT CGC TAT TCT GTG ATG 870Leu Glu Val Thr Leu Ala Gly Trp Glu Pro Arg Arg Tyr Ser Val Met25 30 35GAG GAA ACA GAG AGA GGT TCT TTT GTA GCC AAC CTG GCC AAT GAC CTA 918Glu Glu Thr Glu Arg Gly Ser Phe Val Ala Asn Leu Ala Asn Asp Leu40 45 50GGG CTG GGA GTG GGG GAG CTA GCC GAG CGG GGA GCC CGG GTA GTT TCT 966Gly Leu Gly Val Gly Glu Leu Ala Glu Arg Gly Ala Arg Val Va1 Ser55 60 65GAG GAT AAC GAA CAA GGC TTG CAG CTT GAT CTG CAG ACC GGG CAG TTG1014Glu Asp Asn Glu Gln Gly Leu Gln Leu Asp Leu Gln Thr Gly Gln Leu70 75 80ATA TTA AAT GAG AAG CTG GAC CGG GAG AAG CTG TGT GGC CCT ACT GAG1062Ile Leu Asn Glu Lys Leu Asp Arg Glu Lys Leu Cys Gly Pro Thr Glu85 90 95 100CCC TGT ATA ATG CAT TTC CAA GTG TTA CTG AAA AAA CCT TTG GAA GTA1110Pro Cys Ile Met His Phe Gln Val Leu Leu Lys Lys Pro Leu Glu Val105 110 115TTT CGA GCT GAA CTA CTA GTG ACA GAC ATA AAC GAT CAT TCT CCT GAG1158Phe Arg Ala Glu Leu Leu Val Thr Asp Ile Asn Asp His Ser Pro Glu120 125 130TTT CCT GAA AGA GAA ATG ACC CTG AAA ATC CCA GAA ACT AGC TCC CTT1206Phe Pro Glu Arg Glu Met Thr Leu Lys Ile Pro Glu Thr Ser Ser Leu135 140 145GGG ACT GTG TTT CCT CTG AAA AAA GCT CGG GAC TTG GAC GTG GGC AGC1254Gly Thr Val Phe Pro Leu Lys Lys Ala Arg Asp Leu Asp Val Gly Ser150 155 160AAT AAT GTT CAA AAC TAC AAT ATT TCT CCC AAT TCT CAT TTC CAT GTT1302Asn Asn Val Gln Asn Tyr Asn Ile Ser Pro Asn Ser His Phe His Val165 170 175 180TCC ACT CGC ACC CGA GGG GAT GGC AGG AAA TAC CCA GAG CTG GTG CTG1350Ser Thr Arg Thr Arg Gly Asp Gly Arg Lys Tyr Pro Glu Leu Val Leu185 190 195GAC ACA GAA CTG GAT CGC GAG GAG CAG GCC GAG CTC AGA TTA ACC TTG1398Asp Thr Glu Leu Asp Arg Glu Glu Gln Ala Glu Leu Arg Leu Thr Leu200 205 210ACA GCG GTG GAC GGT GGC TCT CCA CCC CGA TCT GGC ACC GTC CAG ATC1446Thr Ala Val Asp Gly Gly Ser Pro Pro Arg Ser Gly Thr Val Gln Ile215 220 225CTC ATC TTG GTC TTG GAC GCC AAT GAC AAT GCC CCG GAG TTT GTG CAG1494Leu Ile Leu Val Leu Asp Ala Asn Asp Asn Ala Pro Glu Phe Val Gln230 235 240GCG CTC TAC GAG GTG CAG GTC CCA GAG AAC AGC CCA GTA GGC TCC CTA1542Ala Leu Tyr Glu Val Gln Val Pro Glu Asn Ser Pro Val Gly Ser Leu245 250 255 260GTT GTC AAG GTC TCT GCT AGG GAT TTA GAC ACT GGG ACA AAT GGA GAG 1590Val Val Lys Val Ser Ala Arg Asp Leu Asp Thr Gly Thr Asn Gly Glu265 270 275ATA TCA TAC TCC CTT TAT TAC AGC TCT CAG GAG ATA GAC AAA CCT TTT 1638Ile Ser Tyr Ser Leu Tyr Tyr Ser Ser Gln Glu Ile Asp Lys Pro Phe280 285 290GAG CTA AGC AGC CTT TCA GGA GAA ATT CGA CTA ATT AAA AAA CTA GAT 1686Glu Leu Ser Ser Leu Ser Gly Glu Ile Arg Leu Ile Lys Lys Leu Asp295 300 305TTT GAG ACA ATG TCT TCA TAT GAT CTA GAT ATA GAG GCA TCT GAT GGC 1734Phe Glu Thr Met Ser Ser Tyr Asp Leu Asp Ile Glu Ala Ser Asp Gly310 315 320GGG GGA CTT TCT GGA AAA TGC TCT GTC TCT GTT AAG GTG CTG GAT GTT 1782Gly Gly Leu Ser Gly Lys Cys Ser Val Ser Val Lys Val Leu Asp Val325 330 335 340AAC GAT AAC TTC CCG GAA CTA AGT ATT TCA TCA CTT ACC AGC CCT ATT 1830Asn Asp Asn Phe Pro Glu Leu Ser Ile Ser Ser Leu Thr Ser Pro Ile345 350 355CCC GAG AAT TCT CCA GAG ACA GAA GTG GCC CTG TTT AGG ATT AGA GAC 1878Pro Glu Asn Ser Pro Glu Thr Glu Val Ala Leu Phe Arg Ile Arg Asp360 365 370CGA GAC TCT GGA GAA AAT GGA AAA ATG ATT TGC TCA ATT CAG GAT GAT 1926Arg Asp Ser Gly Glu Asn Gly Lys Met Ile Cys Ser Ile Gln Asp Asp375 380 385GTT CCT TTT AAG CTA AAA CCT TCT GTT GAG AAT TTC TAC AGG CTG GTA 1974Val Pro Phe Lys Leu Lys Pro Ser Val Glu Asn Phe Tyr Arg Leu Val390 395 400ACA GAA GGG GCG CTG GAC AGA GAG ACC AGA GCC GAG TAC AAC ATC ACC 2022Thr Glu Gly Ala Leu Asp Arg Glu Thr Arg Ala Glu Tyr Asn Ile Thr405 410 415 420ATC ACC ATC ACA GAC TTG GGG ACT CCA AGG CTG AAA ACC GAG CAG AGC 2070Ile Thr Ile Thr Asp Leu Gly Thr Pro Arg Leu Lys Thr Glu Gln Ser425 430 435ATA ACC GTG CTG GTG TCG GAC GTC AAT GAC AAC GCC CCC GCC TTC ACC 2118Ile Thr Val Leu Val Ser Asp Val Asn Asp Asn Ala Pro Ala Phe Thr440 445 450CAA ACC TCC TAC ACC CTG TTC GTC CGC GAG AAC AAC AGC CCC GCC CTG 2166Gln Thr Ser Tyr Thr Leu Phe Val Arg Glu Asn Asn Ser Pro Ala Leu455 460 465CAC ATC GGC AGT GTC AGC GCC ACA GAC AGA GAC TCG GGC ACC AAC GCC 2214His Ile Gly Ser Val Ser Ala Thr Asp Arg Asp Ser Gly Thr Asn Ala470 475 480CAG GTC ACC TAC TCG CTG CTG CCG CCC CAG GAC CCG CAC CTG CCC CTA 2262Gln Val Thr Tyr Ser Leu Leu Pro Pro Gln Asp Pro His Leu Pro Leu485 490 495 500ACC TCC CTG GTC TCC ATT AAC ACG GAC AAC GGC CAC CTG TTC GCT CTC 2310Thr Ser Leu Val Ser Ile Asn Thr Asp Asn Gly His Leu Phe Ala Leu505 510 515CAG TCG CTG GAC TAC GAG GCC CTG CAG GCT TTC GAG TTC CGC GTG GGC 2358Gln Ser Leu Asp Tyr Glu Ala Leu Gln Ala Phe Glu Phe Arg Val Gly520 525 530GCC ACA GAC CGC GGC TTC CCG GCG CTG AGC AGC GAG GCG CTG GTG CGA 2406Ala Thr Aep Arg Gly Phe Pro Ala Leu Ser Ser Glu Ala Leu Val Arg535 540 545GTG CTG GTG CTG GAC GCC AAC GAC AAC TCG CCC TTC GTG CTG TAC CCG 2454Val Leu Val Leu Asp Ala Asn Asp Asn Ser Pro Phe Val Leu Tyr Pro550 555 560CTG CAG AAC GGC TCC GCG CCC TGC ACC GAG CTG GTG CCC CGG GCG GCC 2502Leu Gln Asn Gly Ser Ala Pro Cys Thr Glu Leu Val Pro Arg Ala Ala565 570 575 580GAG CCG GGC TAC CTG GTG ACC AAG GTG GTG GCG GTG GAC GGC GAC TCG 2550Glu Pro Gly Tyr Leu Val Thr Lys Val Val Ala Val Asp Gly Asp Ser585 590 595GGC CAG AAC GCC TGG CTG TCG TAC CAG CTG CTC AAG GCC ACG GAG CCC 2598Gly Gln Asn Ala Trp Leu Ser Tyr Gln Leu Leu Lys Ala Thr Glu Pro600 605 610GGG CTG TTC GGC GTG TGG GCG CAC AAT GGC GAG GTG CGC ACC GCC AGG 2646Gly Leu Phe Gly Val Trp Ala His Ash Gly Glu Val Arg Thr Ala Arg615 620 625CTG CTG AGC GAG CGC GAC GTG GCC AAG CAC AGG CTA GTG GTG CTG GTC 2694Leu Leu Ser Glu Arg Asp Val Ala Lys His Arg Leu Val Val Leu Val630 635 640AAG GAC AAT GGC GAG CCT CCG CGC TCG GCC ACA GCC ACG CTG CAA GTG 2742Lys Asp Asn Gly Glu Pro Pro Arg Ser Ala Thr Ala Thr Leu Gln Val645 650 655 660CTC CTG GTG GAC GGC TTC TCT CAG CCC TAC CTG CCG CTC CCA GAG GCG 2790Leu Leu Val Asp Gly Phe Ser Gln Pro Tyr Leu Pro Leu Pro Glu Ala665 670 675GCC CCG GCC CAA GCC CAG GCC GAC TCG CTT ACC GTC TAC CTG GTG GTG 2838Ala Pro Ala Gln Ala Gln Ala Asp Ser Leu Thr Val Tyr Leu Val Val680 685 690GCA TTG GCC TCG GTG TCT TCG CTC TTC CTC TTC TCG GTG TTC CTG TTC 2886Ala Leu Ala Ser Val Ser Ser Leu Phe Leu Phe Ser Val Phe Leu Phe695 700 705GTG GCA GTG CGG CTG TGC AGG AGG AGC AGG GCG GCC TCA GTG GGT CGC 2934Val Ala Val Arg Leu Cys Arg Arg Ser Arg Ala Ala Ser Val Gly Arg710715 720TGC TCG GTG CCC GAG GGC CCC TTT CCA GGG CAT CTG GTG GAC GTG AGC 2982Cys Ser Val Pro Glu Gly Pro Phe Pro Gly His Leu Val Asp Val Ser725 730 735 740GGC ACC GGG ACC CrT TCC CAG AGC TAC CAG TAC GAG GTG TGT CTG ACG3030Gly Thr Gly Thr Leu Ser Gln Ser Tyr Gln Tyr Glu Val Cys Leu Thr745 750 755GGA GGC TCT GAA AGT AAT GAT TTC AAG TTC TTG AAG CCT ATA TTC CCA3078Gly Gly Ser Glu Ser Asn Asp Phe Lys Phe Leu Lys Pro Ile Phe Pro760 765 770AAT ATT GTA AGC CAG GAC TCT AGG AGG AAA TCA GAA TTT CTA GAA3123Asn Ile Val Ser Gln Asp Ser Arg Arg Lys Ser Glu Phe Leu Glu775 780 785TAATGTAGGT ATCTGTAGCT TTCCGACCGT CTGTTAATTT TGTCTTCCTC ACTTTTCACC 3183TTAGTTTTTT TTAACCCTTT AGTAATCTTG AATTCTACTT TTTTTTAAAT TTCTACTGTT 3243GTCTTTAGTA ATGTTACTCA TTTCCTTTGT CTGATTGTTA GTTTTCAAAT TATTGTATTA 3303TTATAAATAT TTTATATCAG GAAAGTTCAT ATTTCTGAAT AAATTAATAG 3353(2)SEQ ID NO110的信息(i)序列特征(A)長(zhǎng)度787氨基酸(B)類型氨基酸(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO110Met Glu Pro Ala Gly Glu Arg Phe Pro Glu Gln Arg Gln Val Leu Ile1 5 10 15Leu Leu Leu Leu Leu Glu Val Thr Leu Ala Gly Trp Glu Pro Arg Arg20 25 30Tyr Ser Val Mer Glu Glu Thr Glu Arg Gly Ser Phe Val Ala Asn Leu35 40 45Ala Asn Asp Leu Gly Leu Gly Val Gly Glu Leu Ala Glu Arg Gly AlaS0 55 60Arg Val Val Ser Glu Asp Asn Glu Gln Gly Leu Gln Leu Asp Leu Gln65 70 75 80Thr Gly Gln Leu Ile Leu Asn Glu Lys Leu Asp Arg Glu Lys Leu Cys85 90 95Gly Pro Thr Glu Pro Cys Ile Met His Phe Gln Val Leu Leu Lys Lys100 105 110Pro Leu Glu Val Phe Arg Ala Glu Leu Leu Val Thr Asp Ile Asn Asp115 120 125
His Ser Pro Glu Phe Pro Glu Arg Glu Met Thr Leu Lys Ile Pro Glu130 135 140Thr Ser Ser Leu Gly Thr Val Phe Pro Leu Lys Lys Ala Arg Asp Leu145 150 155 160Asp Val Gly Ser Asn Asn Val Gln Asn Tyr Asn Ile Ser Pro Asn Ser165 170 175His Phe His Val Ser Thr Arg Thr Arg Gly Asp Gly Arg Lys Tyr Pro180 185 190Glu Leu Val Leu Asp Thr Glu Leu Asp Arg Glu Glu Gln Ala Glu Leu195 200 205Arg Leu Thr Leu Thr Ala Val Asp Gly Gly Ser Pro Pro Arg Ser Gly210 215 220Thr Val Gln Ile Leu Ile Leu Val Leu Asp Ala Asn Asp Asn Ala Pro225 230 23S 240Glu Phe Val Gln Ala Leu Tyr Glu Val Gln Val Pro Glu Asn Ser Pro245 250 255Val Gly Ser Leu Val Val Lys Val Ser Ala Arg Asp Leu Asp Thr Gly260 265 270Thr Asn Gly Glu Ile Ser Tyr Ser Leu Tyr Tyr Ser Ser Gln Glu Ile275 280 285Asp Lys Pro Phe Glu Leu Ser Ser Leu Ser Gly Glu Ile Arg Leu Ile290 295 300Lys Lys Leu Asp Phe Glu Thr Met Ser Ser Tyr Asp Leu Asp Ile Glu305 310 315 320Ala Ser Asp Gly Gly Gly Leu Ser Gly Lys Cys Ser Val Ser Val Lys325 330 335Val Leu Asp Val Asn Asp Asn Phe Pro Glu Leu Ser Ile Ser Ser Leu340 345 350Thr Ser Pro Ile Pro Glu Ash Ser Pro Glu Thr Glu Val Ala Leu Phe355 360 365Arg Ile Arg Asp Arg Asp Ser Gly Glu Asn Gly Lys Met Ile Cys Ser370 375 380Ile Gln Asp Asp Val Pro Phe Lys Leu Lys Pro Ser Val Glu Asn Phe385 390 395 400Tyr Arg Leu Val Thr Glu Gly Ala Leu Asp Arg Glu Thr Arg Ala Glu405 410 415Tyr Asn Ile Thr Ile Thr Ile Thr Asp Leu Gly Thr Pro Arg Leu Lys420 425 430Thr Glu Gln Ser Ile Thr Val Leu Val Ser Asp Val Asn Asp Asn Ala435 440 445
Pro Ala Phe Thr Gln Thr Ser Tyr Thr Leu Phe Val Arg Glu Asn Asn450 455 460Ser Pro Ala Leu His Ile Gly Ser Val Ser Ala Thr Asp Arg Asp Ser465 470 475 480Gly Thr Asn Ala Gln Val Thr Tyr Ser Leu Leu Pro Pro Gln Asp Pro485 490 495His Leu Pro Leu Thr Ser Leu Val Ser Ile Asn Thr Asp Asn Gly His500 505 510Leu Phe Ala Leu Gln Ser Leu Asp Tyr Glu Ala Leu Gln Ala Phe Glu515 520 525Phe Arg Val Gly Ala Thr Asp Arg Gly Phe Pro Ala Leu Ser Ser Glu530 535 540Ala Leu Val Arg Val Leu Val Leu Asp Ala Asn Asp Asn Ser Pro Phe545 550 555 560Val Leu Tyr Pro Leu Gln Asn Gly Ser Ala Pro Cys Thr Glu Leu Val565 570 575Pro Arg Ala Ala Glu Pro Gly Tyr Leu Val Thr Lys Val Val Ala Val580 585 590Asp Gly Asp Ser Gly Gln Asn Ala Trp Leu Ser Tyr Gln Leu Leu Lys595 600 605Ala Thr Glu Pro Gly Leu Phe Gly Val Trp Ala His Asn Gly Glu Val610 615 620Arg Thr Ala Arg Leu Leu Ser Glu Arg Asp Val Ala Lys His Arg Leu625 630 635 640Val Val Leu Val Lys Asp Asn Gly Glu Pro Pro Arg Ser Ala Thr Ala645 650 655Thr Leu Gln Val Leu Leu Val Asp Gly Phe Ser Gln Pro Tyr Leu Pro660 665 670Leu Pro Glu Ala Ala Pro Ala Gln Ala Gln Ala Asp Ser Leu Thr Val675 680 685Tyr Leu Val Val Ala Leu Ala Ser Val Ser Ser Leu Phe Leu Phe Ser690 695 700Val Phe Leu Phe Val Ala Val Arg Leu Cys Arg Arg Ser Arg Ala Ala705 710 715 720
Ser Val Gly Arg Cys Ser Val Pro Glu Gly Pro Phe Pro Gly His Leu725 730 735Val Asp Val Ser Gly Thr Gly Thr Leu Ser Gln Ser Tyr Gln Tyr Glu740 745 750Val Cys Leu Thr Gly Gly Ser Glu Ser Asn Asp Phe Lys Phe Leu Lys755 760 765Pro Ile Phe Pro Asn Ile Val Ser Gln Asp Ser Arg Arg Lys Ser Glu770 775 780Phe Leu Glu785(2)SEQ ID NO111的信息(i)序列特征(A)長(zhǎng)度3033堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(ix)特征(A)名稱/鍵CDS(B)定位138..2528(xi)序列描述SEQ ID NO111GTGATTGGAC GTGTTTTTGT GACTATTTGG GAAGAAGACA CCTTCCTAAT CAGATTTACT 60CCAATATCTT CCCGGACCCT CATGAGTGGA TTGCAATTGA CTTGAAGAAG CAGCACCCTC120AGGACTGAAT CTGAACA ATG GAG ACA GCA CTA GCA AAA ATA CCA CAG CAA 170Met Glu Thr Ala Leu Ala Lys Ile Pro Gln Gln1 5 10AGG CAA GTC TTT TTT CTT ACT ATA TTG TCG TTA TTG TGG AAG TCT AGC 218Arg Gln Val Phe Phe Leu Thr Ile Leu Ser Leu Leu Trp Lys Ser Ser15 20 25TCT GAG GCC ATT AGA TAT TCC ATG CCA GAA GAA ACA GAG AGT GGC TAT 266Ser Glu Ala Ile Arg Tyr Ser Met Pro Glu Glu Thr Glu Ser Gly Tyr30 35 40ATG GTG GCT AAC CTG GCG AAA GAT CTG GGG ATC AGG GTT GGA GAA CTG 314Met Val Ala Asn Leu Ala Lys Asp Leu Gly Ile Arg Val Gly Glu Leu45 50 55TCC TCT AGA GGA GCT CAA ATC CAT TAC AAA GGA AAC AAA GAA CTT TTG 362Ser Ser Arg Gly Ala Gln Ile His Tyr Lys Gly Asn Lys Glu Leu Leu60 65 70 75CAG CTG GAT GCA GAG ACT GGG AAT TTG TTC TTA AAG GAA AAA CTA GAC 410Gln Leu Asp Ala Glu Thr Gly Asn Leu Phe Leu Lys Glu Lys Leu Asp80 85 90AGA GAA CTG CTG TGT GGA GAG ACA GAA CCC TGT GTG CTG AAC TTC CAG 458Arg Glu Leu Leu Cys Gly Glu Thr Glu Pro Cys Val Leu Asn Phe Gln95 100 105ATC ATA CTG GAA AAC CCT ATG CAG TTC TTC CAA ACT GAA CTG CAG CTC 506Ile Ile Leu Glu Asn Pro Mer Gln Phe Phe Gln Thr Glu Leu Gln Leu110 115 120ACA GAT ATA AAC GAC CAT TCT CCA GAG TTC CCC AAC AAG AAA ATG CTT 554Thr Asp Ile Asn Asp His Ser Pro Glu Phe Pro Asn Lys Lys Met Leu125 130 135CTA ACA ATT CCT GAG AGT GCC CAT CCA GGG ACT GTG TTT CCT CTG AAG 602Leu Thr Ile Pro Glu Ser Ala His Pro Gly Thr Val Phe Pro Leu Lys140 145 150 155GCA GCT CGG GAC TCT GAC ATA GGG AGC AAC GCT GTT CAG AAC TAC ACA 650Ala Ala Arg Asp Ser Asp Ile Gly Ser Asn Ala Val Gln Asn Tyr Thr160 165 170GTC AAT CCC AAC CTC CAT TTC CAC GTC GTT ACT CAC AGT CGC ACA GAT 698Val Asn Pro Asn Leu His Phs His Val Val Thr His Ser Arg Thr Asp175 180 185GGC AGG AAA TAC CCA GAG CTG GTG CTG GAC AGA GCC CTG GAT AGG GAG 746Gly Arg Lye Tyr Pro Glu Leu Val Leu Asp Arg Ala Leu Asp Arg Glu190 195 200GAG CAG CCT GAG CTC ACT TTA ATC CTC ACT GCT CTG GAT GGT GGA GCT 794Glu Gln Pro Glu Leu Thr Leu Ile Leu Thr Ala Leu Asp Gly Gly Ala205 210 215CCT TCC AGG TCA GGA ACC ACC ACA GTT CAC ATA GAA GTT GTG GAC ATC 842Pro Ser Arg Ser Gly Thr Thr Thr Val His Ile Glu Val Val Asp Ile220 225230 235AAT GAT AAC TCC CCC CAG TTT GTA CAG TCA CTC TAT AAG GTG CAA GTT 890Asn Asp Asn Ser Pro Gln Phe Val Gln Ser Leu Tyr Lys Val Gln Val240 245 250CCT GAG AAT AAT CCC CTC AAT GCC TTT GTT GTC ACG GTC TCT GCC ACG 938Pro Glu Asn Asn Pro Leu Asn Ala Phe Val Val Thr Val Ser Ala Thr255 260 265GAT TTA GAT GCT GGG GTA TAT GGC AAT GTG ACC TAT TCT CTG TTT CAA 986Asp Leu Asp Ala Gly Val Tyr Gly Asn Val Thr Tyr Ser Leu Phe Gln270 275 280GGG TAT GGG GTA TTT CAA CCA TTT GTA ATA GAC GAA ATC ACT GGA GAA1034Gly Tyr Gly Val Phe Gln Pro Phe Val Ile Asp Glu Ile Thr Gly Glu285 290 295ATC CAT CTG AGC AAA GAG CTG GAT TTT GAG GAA ATT AGC AAT CAT AAC1082Ile His Leu Ser Lys Glu Leu Asp Phe Glu Glu Ile Ser Asn His Asn300 305 310 315ATA GAA ATC GCA GCC ACA GAT GGA GGA GGC CTT TCA GGA AAA TGC ACT1130Ile Glu Ile Ala Ala Thr Asp Gly Gly Gly Leu Ser Gly Lys Cys Thr320 325 330GTG GCT GTA CAG GTG TTG GAT GTG AAT GAC AAC GCC CCA GAG TTG ACA1178Val Ala Val Gln Val Leu Asp Val Asn Asp Asn Ala Pro Glu Leu Thr335 340 345ATT AGG AAG CTC ACA GTC CTG GTC CCA GAA AAT TCC GCA GAG ACT GTA1226Ile Arg Lys Leu Thr Val Leu Val Pro Glu Asn Ser Ala Glu Thr Val350 355 360GTT GCT GTT TTT AGT GTT TCT GAT TCT GAT TCG GGG GAC AAT GGA AGG 1274Val Ala Val Phe Ser Val Ser Asp Ser Asp Ser Gly Asp Asn Gly Arg365 370 375ATG GTG TGT TCT ATT CCG AAC AAT ATC CCA TTT CTC CTG AAA CCC ACA 1322Met Val Cys Ser Ile Pro Asn Asn Ile Pro Phe Leu Leu Lys Pro Thr380 385 390 395TTT GAG AAT TAT TAC ACG TTA GTG ACT GAG GGG CCA CTT GAT AGA GAG 1370Phe Glu Asn Tyr Tyr Thr Leu Val Thr Glu Gly Pro Leu Asp Arg Glu400 405 410AAC AGA GCT GAG TAC AAC ATC ACC ATC ACG GTC TCA GAT CTG GGC ACA 1418Asn Arg Ala Glu Tyr Asn Ile Thr Ile Thr Val Ser Asp Leu Gly Thr415 420 425CCC AGG CTC ACA ACC CAG CAC ACC ATA ACA GTG CAA GTG TCC GAC ATC 1466Pro Arg Leu Thr Thr Gln His Thr Ile Thr Val Gln Val Ser Asp Ile430 435 440AAC GAC AAC GCC CCT GCC TTC ACC CAA ACC TCC TAC ACC ATG TTT GTC 1514Asn Asp Asn Ala Pro Ala Phe Thr Gln Thr Ser Tyr Thr Met Phe Val445 450 455CAC GAG AAC AAC AGC CCC GCC CTG CAC ATA GGC ACC ATC AGT GCC ACA 1562His Glu Asn Asn Ser Pro Ala Leu His Ile Gly Thr Ile Ser Ala Thr460 465 470 475GAC TCA GAC TCA GGC TCC AAT GCC CAC ATC ACC TAC TCG CTG CTG CCG 1610Asp Ser Asp Ser Gly Ser Asn Ala His Ile Thr Tyr Ser Leu Leu Pro480 485 490CCT GAT GAC CCG CAG CTG GCC CTC GAC TCA CTC ATC TCC ATC AAT GTT 1658Pro Asp Asp Pro Gln Leu Ala Leu Asp Ser Leu Ile Ser Ile Asn Val495 500 505GAC AAT GGG CAG CTG TTC GCG CTC AGA GCT CTA GAC TAT GAG GCA CTG 1706Asp Asn Gly Gln Leu Phe Ala Leu Arg Ala Leu Asp Tyr Glu Ala Leu510 515 520CAG TCC TTC GAG TTC TAC GTG GGC GCT ACA GAT GGA GGC TCA CCC GCG 1754Gln Ser Phe Glu Phe Tyr Val Gly Ala Thr Asp Gly Gly Ser Pro Ala525 530 535CTC AGC AGC CAG ACT CTG GTG CGG ATG GTG GTG CTG GAT GAC AAT GAC 1802Leu Ser Ser Gln Thr Leu Val Arg Met Val Val Leu Asp Asp Asn Asp540 545 550 555AAT GCC CCC TTC GTG CTC TAC CCA CTG CAG AAT GCC TCA GCA CCC TGT 1850Asn Ala Pro Phe Val Leu Tyr Pro Leu Gln Asn Ala Ser Ala Pro Cys560 565 570ACT GAG CTA CTG CCT AGG GCA GCA GAG CCC GGC TAC CTG ATC ACC AAA 1898Thr Glu Leu Leu Pro Arg Ala Ala Glu Pro Gly Tyr Leu Ile Thr Lys575 580 585GTG GTG GCT GTG GAT CGC GAC TCT GGA CAG AAT GCT TGG CTG TCG TTC 1946Val Val Ala Val Asp Arg Asp Ser Gly Gln Asn Ala Trp Leu Ser Phe590 595 600CAG CTA CTT AAA GCT ACA GAG CCA GGG CTG TTC AGT GTA TGG GCA CAC 1994Gln Leu Leu Lys Ala Thr Glu Pro Gly Leu Phe Ser Val Trp Ala His605 610 615AAT GGT GAA GTG CGC ACC ACT AGG CTG CTG AGT GAG CGA GAT GCT CAG2042Asn Gly Glu Val Arg Thr Thr Arg Leu Leu Ser Glu Arg Asp Ala Gln620 625 630 635AAG CAC AAG CTA CTG CTG CTG GTC AAG GAC AAT GGC GAT CCT CTG CGC2090Lys His Lys Leu Leu Leu Leu Val Lys Asp Asn Gly Asp Pro Leu Arg640 645 650TCT GCC AAT GTC ACT CTT CAC GTG CTA GTG GTG GAT GGC TTC TCG CAG2138Ser Ala Asn Val Thr Leu His Val Leu Val Val Asp Gly Phe Ser Gln655 660 665CCT TAC CTA CCA TTG GCT GAG GTG GCA CAG GAT TCC ATG CAA GAT AAT2186Pro Tyr Leu Pro Leu Ala Glu Val Ala Gln Asp Ser Met Gln Asp Asn670 675 680TAC GAC GTT CTC ACA CTG TAC CTA GTC ATT GCC TTG GCA TCT GTA TCT2234Tyr Asp Val Leu Thr Leu Tyr Leu Val Ile Ala Leu Ala Ser Val Ser685 690 695TCT CTC TTC CTC TTG TCT GTA GTG CTG TTT GTG GGG GTG AGG CTG TGC2282Ser Leu Phe Leu Leu Ser Val Val Leu Phe Val Gly Val Arg Leu Cys700 705 710 715AGG AGG GCC AGG GAG GCC TCC TTG GGT GAC TAC TCT GTG CCT GAG GGA2330Arg Arg Ala Arg Glu Ala Ser Leu Gly Asp Tyr Ser Val Pro Glu Gly720 725 730CAC TTT CCT AGC CAC TTG GTG GAT GTC AGC GGT GCC GGG ACC CTG TCC2378His Phe Pro Ser His Leu Val Asp Val Ser Gly Ala Gly Thr Leu Ser735 740 745CAG AGT TAT CAA TAT GAG GTG TGT CTT AAT GGA GGT ACT AGA ACA AAT2426Gln Ser Tyr Gln Tyr Glu Val Cys Leu Asn Gly Gly Thr Arg Thr Asn750 755 760GAG TTT AAC TTT CTT AAA CCA TTG TTT CCT ATC CTT CCG ACC CAG GCT2474Glu Phe Asn Phe Leu Lys Pro Leu Phe Pro Ile Leu Pro Thr Gln Ala765 770 775GCT GCT GCT GAA GAA AGA GAA AAC GCT GTT GTG CAC AAT AGC GTT GGA2522Ala Ala Ala Glu Glu Arg Glu Asn Ala Val Val His Asn Ser Val Gly780 785 790 795TTC TAT TAGAGCACTG ATTTTGAAGT GGTGGTTACC TCATTTTTCC TTAACTATCC 2578Phe TyrCTGATGTAGA ATGGTGTAGT GCCGTGAATC AACTCCTGAG ATATATGTTC ATTTTATCCT 2638TTGTTTTGAA TCAAACTATT CAGATGTGAT CCTACTCTAG AGAATTTGGT TCTACTCCAT 2698TGTGTTTGTT TAGATTTCTA CGCCATACCA GTGCATGCTG GGTTGTTTTT TTTTTTACAA 2758TTATTATAAC TTTGCTTTGG AGGGGAACTC ATATTCGCTG TAACGAATTG GAACCACTTT 2818CATTGTTAGA GATGCCTTGC TTTGTTGTGT TATTTCAGAC AGGGTCTTAA ATTGTAGCCC 2878TGGGTGACCT GAAATGACTA TGTACAGACT GACTTTGAAT TTGTGGCAGT CCATCTGCCT 2938CTGTTGTCCT ATGTTGGGAT TGTGAGCATG CATGAGTAGG CTCAGCTGTG GTGAGCGACC 2998TTAATAAAAA TCAAATACTA AAAAAAAAAA AAAAA 3033(2)SEQ ID NO112的信息(i)序列特征(A)長(zhǎng)度797氨基酸(B)類型氨基酸(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO112Met Glu Thr Ala Leu Ala Lys Ile Pro Gln Gln Arg Gln Val Phe Phe1 5 10 15Leu Thr Ile Leu Ser Leu Leu Trp Lys Ser Ser Ser Glu Ala Ile Arg20 25 30Tyr Ser Met Pro Glu Glu Thr Glu Ser Gly Tyr Met Val Ala Asn Leu35 40 45Ala Lys Asp Leu Gly Ile Arg Val Gly Glu Leu Ser Ser Arg Gly Ala50 55 60Gln Ile His Tyr Lys Gly Asn Lys Glu Leu Leu Gln Leu Asp Ala Glu65 70 75 80Thr Gly Asn Leu Phe Leu Lys Glu Lys Leu Asp Arg Glu Leu Leu Cys85 90 95Gly Glu Thr Glu Pro Cys Val Leu Asn Phe Gln Ile Ile Leu Glu Asn100 105 110Pro Met Gln Phe Phe Gln Thr Glu Leu Gln Leu Thr Asp Ile Asn Asp115 120 125His Ser Pro Glu Phe Pro Asn Lys Lys Met Leu Leu Thr Ile Pro Glu130 135 140Ser Ala His Pro Gly Thr val Phe Pro Leu Lys Ala Ala Arg Asp Ser145 150 155 160Asp Ile Gly Ser Asn Ala Val Gln Asn Tyr Thr Val Asn Pro Asn Leu165 170 175His Phe His Val Val Thr His Ser Arg Thr Asp Gly Arg Lys Tyr Pro180 185 190Glu Leu Val Leu Asp Arg Ala Leu Asp Arg Glu Glu Gln Pro Glu Leu195 200 205Thr Leu Ile Leu Thr Ala Leu Asp Gly Gly Ala Pro Ser Arg Ser Gly210 215 220Thr Thr Thr Val His Ile Glu Val Val Asp Ile Asn Asp Asn Ser Pro225 230 235 240
Gln Phe Val Gln Ser Leu Tyr Lys Val Gln Val Pro Glu Asn Asn Pro245 250 255Leu Asn Ala Phe Val Val Thr Val Ser Ala Thr Asp Leu Asp Ala Gly260 265 270Val Tyr Gly Asn Val Thr Tyr Ser Leu Phe Gln Gly Tyr Gly Val Phe275 280 285Gln Pro Phe Val Ile Asp Glu Ile Thr Gly Glu Ile His Leu Ser Lys290 295 300Glu Leu Asp Phe Glu Glu Ile Ser Ash His Asn Ile Glu Ile Ala Ala305 310 315 320Thr Asp Gly Gly Gly Leu Ser Gly Lys Cys Thr Val Ala Val Gln Val325 330 335Leu Asp Val Asn Asp Asn Ala Pro Glu Leu Thr Ile Arg Lys Leu Thr340 345 350Val Leu Val Pro Glu Asn Ser Ala Glu Thr Val Val Ala Val Phe Ser355 360 365Val Ser Asp Ser Asp Ser Gly Asp Asn Gly Arg Met Val Cye Ser Ile370 375 380Pro Asn Asn Ile Pro Phe Leu Leu Lys Pro Thr Phe Glu Asn Tyr Tyr385 390 395 400Thr Leu Val Thr Glu Gly Pro Leu Asp Arg Glu Asn Arg Ala Glu Tyr405 410 415Asn Ile Thr Ile Thr Val Ser Asp Leu Gly Thr Pro Arg Leu Thr Thr420 425 430Gln His Thr Ile Thr Val Gln Val Ser Asp Ile Asn Asp Asn Ala Pro435 440 445Ala Phe Thr Gln Thr Ser Tyr Thr Met Phe Val His Glu Asn Asn Ser450 455 460Pro Ala Leu His Ile Gly Thr Ile Ser Ala Thr Asp Ser Asp Ser Gly465 470 475 480Ser Asn Ala His Ile Thr Tyr Ser Leu Leu Pro Pro Asp Asp Pro Gln485 490 495Leu Ala Leu Asp Ser Leu Ile Ser Ile Asn Val Asp Asn Gly Gln Leu500 505 510Phe Ala Leu Arg Ala Leu Asp Tyr Glu Ala Leu Gln Ser Phe Glu Phe515 520 525Tyr Val Gly Ala Thr Asp Gly Gly Ser Pro Ala Leu Ser Ser Gln Thr530 535 540Leu Val Arg Met Val Val Leu Asp Asp Asn Asp Asn Ala Pro Phe Val545 550 555 560Leu Tyr Pro Leu Gln Asn Ala Ser Ala Pro Cys Thr Glu Leu Leu Pro565 570 575
Arg Ala Ala Glu Pro Gly Tyr Leu Ile Thr Lys Val Val Ala Val Asp580 585 590Arg Asp Ser Gly Gln Asn Ala Trp Leu Ser Phe Gln Leu Leu Lys Ala595 600 605Thr Glu Pro Gly Leu Phe Ser Val Trp Ala His Asn Gly Glu Val Arg610 615 620Thr Thr Arg Leu Leu Ser Glu Arg Asp Ala Gln Lys His Lys Leu Leu625 630 635 640Leu Leu Val Lys Asp Asn Gly Asp Pro Leu Arg Ser Ala Asn Val Thr645 650 655Leu His Val Leu Val Val Asp Gly Phe Ser Gln Pro Tyr Leu Pro Leu660 665 670Ala Glu Val Ala Gln Asp Ser Met Gln Asp Asn Tyr Asp Val Leu Thr675 680 685Leu Tyr Leu Val Ile Ala Leu Ala Ser Val Ser Ser Leu Phe Leu Leu690 695 700Ser Val Val Leu Phe Val Gly Val Arg Leu Cys Arg Arg Ala Arg Glu705 710 715 720Ala Ser Leu Gly Asp Tyr Ser Val Pro Glu Gly His Phe Pro Ser His725 730 735Leu Val Asp Val Ser Gly Ala Gly Thr Leu Ser Gln Ser Tyr Gln Tyr740 745 750Glu Val Cye Leu Asn Gly Gly Thr Arg Thr Asn Glu Phe Asn Phe Leu755 760 765Lys Pro Leu Phe Pro Ile Leu Pro Thr Gln Ala Ala Ala Ala Glu Glu770 775 780Arg Glu Asn Ala Val Val His Asn Ser Val Gly Phe Tyr785 790 795(2)SEQ ID NO113的信息(i)序列特征(A)長(zhǎng)度2347堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(xi)序列描述SEQ ID NO113AAAACACGGG GGAAATGACA GTAGCAAAGA ATCTGGACTA TGAAGAATGC TCATTGTATG60AAATGGAAAT ACAGGCTGAA GATGTGGGGG CGCTTCTGGG GAGGAGCAAA GTGCTAATTA 120TGGTAGAAGA TGTAAATGAC AATCGGCCAG AAGTGACCAT TACATCCTTG TTTAACCCGG 180TATTGGAAAA TTCTCTTCCC GGGACAGTAA TTGCCTTCTT GAATGTGCAT GACCGAGACT 240CTGGAAAGAA CGGCCAAGTT GTCTGTTACA CGCATGATAA CTTACCTTTT AAATTAGAAA 300AGTCAATAGA TAATTATTAT AGATTGGTGA CATGGAAATA TTTGGACCGA GAAAAAGTCT 360CCATCTACAA TATCACAGTG ATAGCCTCAG ATCTAGGAGC CCACTCTGTC ACTGAAACTT 420ACATTGCCCT GATTGTGGCA GACACTAATG ACAACCCTCC TCGTTTTCCT CACACCTCCT 480ACACAGCCTA TATTCCAGAG AACAACCTGA GGGGCGCCTC CATCTTCTCA CTGACTGCAC 540ATGATCCTGA CAGTCAGGAA AATGCACAGG TCACTTACTC TGTGTCTGAG GACACCATAC 600AGGGAGTGCC TTTGTCCTCT TATATCTCCA TCAACTCAGA TACTGGTGTC CTGTATGCAC 660TGCACTCTTT TGACTTCGAG AAGATACAAG ACTTGCAGCT ACTGGTTGTT GCCACTGACA 720GTGGAAGCCC ACCTCTCAGC AGCAATGTGT CATTGAGCTT GTTTGTGTTG GACCAGAACG 780ACAACGCACC TGAGATTCTA TATCCTAGCT TCCCCACAGA TGGCTCCACT GGTGTGGAAC 840TAGCACCCCG CTCTGCACAG CCTGGATACC TAGTGACCAA AGTGGTGGCA GTGGACAAAG 900ACTCAGGACA GAATGCTTGG CTGTCCTACC GTCTGCTGAA GGCCAGCGAA CCTGGGCTCT 960TCTCTGTAGG ACTTCACACG GGTGAGGTGC GTACAGCGAG GGCCCTGCTG GACAGAGATG 1020CTCTCAAACA GAATCTGGTG ATGGCCGTGC AGGACCATGG CCAACCCCCT CTCTCGGCCA 1080CTGTAACTCT CACTGTGGCA GTGGCTAACA GCATCCCTGA GGTGTTGGCT GACTTGAGCA 1140GCATTAGGAC CCCTGGGGTA CCAGAGGATT CTGATATCAC GCTCCACCTG GTGGTGGCAG 1200TGGCTGTGGT CTCCTGTGTC TTCCTTGTCT TTGTCATTGT CCTCCTAGCT CTCAGGCTTC 1260AGCGCTGGCA GAAGTCTCGC CAGCTCCAGG GCTCCAAAGG TGGATTGGCT CCTGCACCTC 1320CATCACATTT TGTGGGCATC GACGGGGTAC AGGCTTTTCT ACAAACCTAT TCTCATGAAG 1380TCTCGCTCAC TTCAGGCTCC CAGACAAGCC ACATTATCTT TCCTCAGCCC AACTATGCAG 1440ACATGCTCAT TAACCAAGAA GGCTGTGAGA AAAATGATTC CTTATTAACA TCCATAGATT 1500TTCATGAGAG TAACCGTGAA GATGCTTGCG CCCCGCAAGC CCCGCCCAAC ACTGACTGGC 1560GTTTCTCTCA AGCCCAGAGA CCCGGCACGA GCGGATCCCA AAATGGGGAT GAAACCGGCA 1620CCTGGCCCAA CAACCAGTTC GATACAGAGA TGCTGCAAGC CATGATCTTG GCCTCTGCCA 1680GTGAAGCCGC TGATGGGAGC TCCACTCTGG GAGGGGGCAC TGGCACTATG GGTTTGAGCG 1740CTCGATATGG ACCCCAGTTT ACCCTGCAGC ACGTGCCTGA CTACCGCCAG AACGTGTACA 1800TCCCTGGCAG CAATGCCACA CTGACCAACG CAGCTGGCAA ACGAGATGGC AAGGCTCCGG 1860CAGGCGGCAA TGGCAACAAC AACAAGTCGG GCAAGAAAGA GAAGAAGTAA TATGGAGGCC 1920AGGCCTTGAG CCACAGGGCA GCCTCCCTCC CCAGCCAGTC CAGCTTGTCC TTACTTGTAC 1980CCAGGCCTCA GAATTTCAGG GCTCACCCCA GGATTCTGGT AGGAGCCACA GCCAGGCCAT 2040GCTCCCCGTT GGGAAACAGA AACAAGTGCC CAAGCCAACA CCCCCTCTTT GTACCCTAGG 2100GGGGTTGAAT ATGCAAAGAG AGTTCTGCTG GGACCCCCTA TCCAATCAGT GATTGTACCC 2160ACATAGGTAG CAGGGTTAGT GTGGATACAC ACACACACAC ACACACACAC ACACACACAA 2220CCCTTGTCCT CCGCAGTGCC TGCCACTTTC TGGGACTTTC TCATCCCCCT ACGCCCTTCC 2280TTTATCCTCT CCCACCCAGA CACAGCTGCT GGAGAATAAA TTTGGGGATG CTGATGCTAA 2340AAAAAAA2347(2)SEQ ID NO114的信息(i)序列特征(A)長(zhǎng)度2972堿基對(duì)(B)類型核酸(C)鏈型單股(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型cDNA(ix)特征(A)名稱/鍵CDS(B)定位2..1849(xi)序列描述SEQ ID NOl14A GAG GCT GCT CAC CAC CTG GTC CTC ACG GCC TCG GAT GGC GGC AAG 46Glu Ala Ala His His Leu Val Leu Thr Ala Ser Asp Gly Gly Lys1 5 10 15CCG CCT CGC TCT AGC ACA GTG CGC ATC CAC CTG ACA GTG TTG GAT ACA94Pro Pro Arg Ser Ser Thr Val Arg Ile His Val Thr Val Leu Asp Thr20 25 30AAT GAC AAT GCC CCG GTT TTT CCT CAC CCG ATT TAC CGA GTG AAA GTC 142Asn Asp Asn Ala Pro Val Phe Pro His Pro Ile Tyr Arg Val Lys Val35 40 45CTT GAG AAC ATG CCC CCA GGC ACG CGG CTG CTT ACT GTA ACA GCC AGC 190Leu Glu Asn Met Pro Pro Gly Thr Arg Leu Leu Thr Val Thr Ala Ser50 55 60GAC CCG GAT GAG GGA ATC AAC GGA AAA GTG GCA TAC AAA TTC CGG AAA 238Asp Pro Asp Glu Gly Ile Asn Gly Lys Val Ala Tyr Lys Phe Arg Lys65 70 75ATT AAT GAA AAA CAA ACT CCG TTA TTC CAG CTT AAT GAA AAT ACT GGG 286Ile Asn Glu Lys Gln Thr Pro Leu Phe Gln Leu Asn Glu Asn Thr Gly80 85 90 95GAA ATA TCA ATA GCA AAA AGT CTA GAT TAT GAA GAA TGT TCA TTT TAT 334Glu Ile Ser Ile Ala Lys Ser Leu Asp Tyr Glu Glu Cys Ser Phe Tyr100 105 110GAA ATG GAA ATA CAA GCC GAA GAT GTG GGG GCA CTT CTG GGG AGG ACC 382Glu Met Glu Ile Gln Ala Glu Asp Val Gly Ala Leu Leu Gly Arg Thr115 120 125AAA TTG CTC ATT TCT GTG GAA GAT GTA AAT GAC AAT AGA CCA GAA GTG 430Lys Leu Leu Ile Ser Val Glu Asp Val Asn Asp Asn Arg Pro Glu Val130 135 140ATC ATT ACG TCT TTG TTT AGC CCA GTG TTA GAA AAT TCT CTT CCC GGG 478Ile Ile Thr Ser Leu Phe Ser Pro Val Leu Glu Asn Ser Leu Pro Gly145 150 155ACA GTA ATT GCC TTC TTG AGT GTG CAT GAC CAA GAC TCT GGA AAG AAT 526Thr Val Ile Ala Phe Leu Ser Val His Asp Gln Asp Ser Gly Lys Asn160 165 170 175GGT CAA GTT GTC TGT TAC ACA CGT GAT AAT TTA CCT TTT AAA TTA GAA 574Gly Gln Val Val Cys Tyr Thr Arg Asp Asn Leu Pro Phe Lys Leu Glu180 185 190AAG TCA ATA GGT AAT TAT TAT AGA TTA GTG ACA AGG AAA TAT TTG GAC 622Lys Ser Ile Gly Asn Tyr Tyr Arg Leu Val Thr Arg Lys Tyr Leu Asp195 200 205CGA GAA AAT GTC TCT ATC TAC AAT ATC ACA GTG ATG GCC TCA GAT CTA 670Arg Glu Asn Val Ser Ile Tyr Asn Ile Thr Val Met Ala Ser Asp Leu210 215 220GGA ACA CCA CCT CTG TCC ACT GAA ACT CAA ATC GCT CTG CAC GTG GCA 718Gly Thr Pro Pro Leu Ser Thr Glu Thr Gln Ile Ala Leu His Val Ala225 230 235GAC ATT AAC GAC AAC CCT CCT ACT TTC CCT CAT GCC TCC TAC TCA GCG 766Asp Ile Asn Asp Asn Pro Pro Thr Phe Pro His Ala Ser Tyr Ser Ala240 245 250 255TAT ATC CTA GAG AAC AAC CTG AGA GGA GCC TCC ATC TTT TCC TTG ACT 814Tyr Ile Leu Glu Asn Asn Leu Arg Gly Ala Ser Ile Phe Ser Leu Thr260 265 270GCA CAC GAC CCC GAC AGC CAG GAG AAT GCC CAG GTC ACT TAC TCT GTG 862Ala His Asp Pro Asp Ser Gln Glu Asn Ala Gln Val Thr Tyr Ser Val275 280 285ACC GAG GAC ACG CTG C AG GGG GCG CCC CTG TCC TCG TAT ATC TCC ATC 910Thr Glu Asp Thr Leu Gln Gly Ala Pro Leu Ser Ser Tyr Ile Ser Ile290 295 300AAC TCT GAC ACC GGT GTC CTG TAT GCG CTG CAA TCT TTC GAC TAT GAG 958Asn Ser Asp Thr Gly Val Leu Tyr Ala Leu Gln Ser Phe Asp Tyr Glu305 310 315CAG ATC CGA GAC CTG CAG CTA CTG GTA ACA GCC AGC GAC AGC GGG GAC 1006Gln Ile Arg Asp Leu Gln Leu Leu Val Thr Ala Ser Asp Ser Gly Asp320 325 330 335CCG CCC CTC AGC AGC AAC ATG TCA CTG AGC CTG TTC GTG CTG GAC CAG 1054Pro Pro Leu Ser Ser Asn Met Ser Leu Ser Leu Phe Val Leu Asp Gln340 345 350AAT GAC AAC GCG CCC GAG ATC CTG TAC CCC GCC CTC CCC ACA GAC GGT 1102Asn Asp Asn Ala Pro Glu Ile Leu Tyr Pro Ala Leu Pro Thr Asp Gly355 360 365TCC ACT GGC GTG GAG CTG GCG CCC CGC TCC GCA GAG CGT GGC TAC CTG 1150Ser Thr Gly Val Glu Leu Ala Pro Arg Ser Ala Glu Arg Gly Tyr Leu370 375 380GTG ACC AAG GTG GTG GCG GTG GAC AGA GAC TCG GGC CAG AAC GCC TGG 1198Val Thr Lys Val Val Ala Val Asp Arg Asp Ser Gly Gln Asn Ala Trp385 390 395CTG TCC TAC CGC CTG CTC AAG GCC AGC GAG CCG GGA CTC TTC TCG GTG 1246Leu Ser Tyr Arg Leu Leu Lys Ala Ser Glu Pro Gly Leu Phe Ser Val400 405 410 415GGT CTG CAC ACG GGC GAG GTG CGC ACG GCG CGA GCC CTG CTG GAC AGA 1294Gly Leu His Thr Gly Glu Val Arg Thr Ala Arg Ala Leu Leu Asp Arg420 425 430GAC GCG CTC AAG CAG AGC CTC GTG GTG GCC GTC CAG GAC CAT GGC CAG 1342Asp Ala Leu Lys Gln Ser Leu Val Val Ala Val Gln Asp His Gly Gln435 440 445CCC CCT CTC TCC GCC ACT GTC ACG CTC ACC GTA GCC GTG GCT GAC AGC 1390Pro Pro Leu Ser Ala Thr Val Thr Leu Thr Val Ala Val Ala Asp Ser450 455 460ATC CCC GAA GTC CTG ACC GAG TTG GGC AGT CTG AAG CCT TCG GTC GAC 1438Ile Pro Glu Val Leu Thr Glu Leu Gly Ser Leu Lys Pro Ser Val Asp465 470 475CCG AAC GAT TCG AGC CTT ACA CTC TAT CTC GTG GTG GCA GTG GCT GCC 1486Pro Asn Asp Ser Ser Leu Thr Leu Tyr Leu Val Val Ala Val Ala Ala480 485 490 495ATC TCC TGT GTC TTC CTC GCC TTT GTC GCT GTG CTT CTG GGG CTC AGG 1534Ile Ser Cys Val Phe Leu Ala Phe Val Ala Val Leu Leu Gly Leu Arg500 505 510CTG AGG CGC TGG CAC AAG TCA CGC CTG CTC CAG GAT TCC GGT GGC AGA 1582Leu Arg Arg Trp His Lys Ser Arg Leu Leu Gln Asp Ser Gly Gly Arg515 520 525TTG GTA GGC GTG CCT GCC TCA CAT TTT GTG GGT GTT GAG GAG GTA CAG1630Leu Val Gly Val Pro Ala Ser His Phe Val Gly Val Glu Glu Val Gln530 535 540GCT TTC CTG CAG ACC TAT TCC CAG GAA GTC TCC CTC ACC GCC GAC TCG1678Ala Phe Leu Gln Thr Tyr Ser Gln Glu Val Ser Leu Thr Ala Asp Ser545 550 555CGG AAG AGT CAC CTG ATC TTT CCC CAG CCC AAC TAC GCA GAC ATG CTC1726Arg Lys Ser His Leu Ile Phe Pro Gln Pro Asn Tyr Ala Asp Met Leu560 565 570 575ATC AGT CAG GAG GGC TGT GAG AAA AAT GAT TCT TTG TTA ACA TCC GTA1774Ile Ser Gln Glu Gly Cys Glu Lye Asn Asp Ser Leu Leu Thr Ser Val580 585 590GAT TTT CAT GAA TAT AAG AAT GAA GCT GAT CAT GGT CAG GTG AGT TTA1822Asp Phe His Glu Tyr Lys Asn Glu Ala Asp His Gly Gln Val Ser Leu595 600 605GTT CTT TGC TTG CTT TTA ATT TCC AGA TGAATTTTAT TTGGCATAAA 1869Val Leu Cys Leu Leu Leu Ile Ser Arg610 615TTATGTTTTG AAAAACATTG TGAAGATAGT TGAAAATAAT TTTTAAGGTG TATCACAGAG 1929TTTTGGGTTT ATTTTGGTGG TGTTACCAAA AAATTGAACT CTAATAGTCA TAGGTTATTG 1989TTTCATTTGC TTTTAAACGA CTTGGAAAAG ATTGTTCCAC CATTTTAAAC CTTCCAGTAT 2049TTTATTCCTA TTATCACTCA TTCACTTAAG AAGTAGCTAC CCGTCCATAC TGGTAATTTT 2109GCTATTGTTT GTTTGTGTGT GTGTGTGTGT GTGTGTGTGT GTGTGTGTAT CCCAAACTAG 2169AACTTCAGAA AATTATCAAG AAGTCTAAAG CCTTGTTATT AGCTTAGCAA AAGTAAAATA 2229TATCTCAGAA TTTTTAGGGT TATGTTTAGC ATTTGAACCT GTAACTAGGC TCTTGTATAT 2289TTCTTCACTT TAAACCTCTT TTCTGAGCCC TGTTTCTGTA CCAGTGCCCT TCAAAACTTT 2349AATACTTCTT ACCATCCTTC AAAACATGAA CAAACTTTAA AGATGGATCT TGGTGGGAGA 2409TGAGACTGGT TACTAAATAT TAAGTATGTG AGTCAGTGGT CACCTGGGCT CCATCCCCAT 2469GGAGACATGA AATCTAAAGC CTAGAATGTC CATTGCTCCC CCAAACAAAA AACAAAAGCA 2529AAAACATTAG ATCTGAATTA AAATGTAATT TTAAACTGTT GAAAGTGACT TTTGTAAAAT 2589ATGTAAGAAC ATATTTCAAT ACAATTCCAA TTAGCTGTTT CGGTTGTGCA TTGATGTGAA 2649GTGGTGAGAA TGTTGATATT AAGAACCAAT GTTTCAGGTA CACAAGTTCT AAATAAGCTG 2709ATCAATTCAA TTAAAGTTAT TCAGTCTTGG CTGGACACAG TGCCTCATGT CTGAAATCCC 2769AGCACTTTGG GAGGCTGGGG CAGGAGGACC GCTTGAGCCC CGGGGGTTTG AAACTGCAGT 2829GAGCTATGAT CATGCCACTG CACTCCAGCC TAGGTGGCAG AACTAGACCC TGTCTCTAAA 2889AAAACTATTA TTAGGCCGCG TGCGGTGGCT CACGCCTGTA ATCCCAGCAC TTTGGGAGAC 2949TGAGGTGGGT GGATCACCTG AGC 2972(2)SEQ ID NO115的信息(i)序列特征(A)長(zhǎng)度616氨基酸(B)類型氨基酸(D)拓?fù)浣Y(jié)構(gòu)線性(ii)分子類型蛋白質(zhì)(xi)序列描述SEQ ID NO115Glu Ala Ala His His Leu Val Leu Thr Ala Ser Asp Gly Gly Lys Pro1 5 10 15Pro Arg Ser Ser Thr Val Arg Ile His Val Thr Val Leu Asp Thr Asn20 25 30Asp Asn Ala Pro Val Phe Pro His Pro Ile Tyr Arg Val Lys Val Leu35 40 45Glu Asn Met Pro Pro Gly Thr Arg Leu Leu Thr Val Thr Ala Ser Asp50 55 60Pro Asp Glu Gly Ile Asn Gly Lys Val Ala Tyr Lys Phe Arg Lye Ile65 70 75 80Asn Glu Lys Gln Thr Pro Leu Phe Gln Leu Asn Glu Asn Thr Gly Glu85 90 95Ile Ser Ile Ala Lys Ser Leu Asp Tyr Glu Glu Cys Ser Phe Tyr Glu100 105 110Met Glu Ile Gln Ala Glu Asp Val Gly Ala Leu Leu Gly Arg Thr Lys115 120 125Leu Leu Ile Ser Val Glu Asp Val Asn Asp Asn Arg Pro Glu Val Ile130 135 140Ile Thr Ser Leu Phe Ser Pro Val Leu Glu Asn Ser Leu Pro Gly Thr145 150 155 160Val Ile Ala Phe Leu Ser Val His Asp Gln Asp Ser Gly Lys Asn Gly165 170 175Gln Val Val Cys Tyr Thr Arg Asp Asn Leu Pro Phe Lys Leu Glu Lys180 185 190Ser Ile Gly Asn Tyr Tyr Arg Leu Val Thr Arg Lys Tyr Leu Asp Arg195 200 205Glu Asn Val Ser Ile Tyr Asn Ile Thr Val Met Ala Ser Asp Leu Gly210 215 220Thr Pro Pro Leu Ser Thr Glu Thr Gln Ile Ala Leu His Val Ala Asp225 230 235 240
Ile Asn Asp Asn Pro Pro Thr Phe Pro His Ala Ser Tyr Ser Ala Tyr245 250 255Ile Leu Glu Aan Asn Leu Arg Gly Ala Ser Ile Phe Ser Leu Thr Ala260 265 270His Asp Pro Asp Ser Gln Glu Asn Ala Gln Val Thr Tyr Ser Val Thr275 280 28SGlu Asp Thr Leu Gln Gly Ala Pro Leu Ser Ser Tyr Ile Ser Ile Asn290 295 300Ser Asp Thr Gly Val Leu Tyr Ala Leu Gln Ser Phe Asp Tyr Glu Gln305 310 315 320Ile Arg Asp Leu Gln Leu Leu Val Thr Ala Ser Asp Ser Gly Asp Pro325 330 335Pro Leu Ser Ser Asn Met Ser Leu Ser Leu Phe Val Leu Asp Gln Asn340 345 350Asp Asn Ala Pro Glu Ile Leu Tyr Pro Ala Leu Pro Thr Asp Gly Ser355 360 365Thr Gly Val Glu Leu Ala Pro Arg Ser Ala Glu Arg Gly Tyr Leu Val370 375 380Thr Lys Val Val Ala Val Asp Arg Asp Ser Gly Gln Asn Ala Trp Leu385 390 395 400Ser Tyr Arg Leu Leu Lys Ala Ser Glu Pro Gly Leu Phe Ser Val Gly405 410 415Leu His Thr Gly Glu Val Arg Thr Ala Arg Ala Leu Leu Asp Arg Asp420 425 430Ala Leu Lys Gln Ser Leu Val Val Ala Val Gln Asp His Gly Gln Pro435 440 445Pro Leu Ser Ala Thr Val Thr Leu Thr Val Ala Val Ala Asp Ser Ile450 455 460Pro Glu Val Leu Thr Glu Leu Gly Ser Leu Lys Pro Ser Val Asp Pro465 470 475 480Asn Asp Ser Ser Leu Thr Leu Tyr Leu Val Val Ala Val Ala Ala Ile485 490 495Ser Cys Val Phe Leu Ala Phe Val Ala Val Leu Leu Gly Leu Arg Leu500 505 510Arg Arg Trp His Lys Ser Arg Leu Leu Gln Asp Ser Gly Gly Arg Leu515 520 525Val Gly Val Pro Ala Ser His Phe Val Gly Val Glu Glu Val Gln Ala530 535 540
Phe Leu Gln Thr Tyr Ser Gln Glu Val Ser Leu Thr Ala Asp Ser Arg545 550 555 560Lys Ser Hia Leu Ile Phe Pro Gln Pro Asn Tyr Ala Asp Met Leu Ile565 570 575Ser Gln Glu Gly Cys Glu Lys Asn Asp Ser Leu Leu Thr Ser Val Asp580 585 590Phe His Glu Tyr Lys Asn Glu Ala Asp His Gly Gln Val Ser Leu Val595 600 605Leu Cys Leu Leu Leu Ile Ser Arg610 61權(quán)利要求
1.純化并分離的編碼人原鈣粘著蛋白pc3的多核苷酸序列。
2.純化并分離的編碼人原鈣粘著蛋白pc4的多核苷酸序列。
3.純化并分離的編碼大鼠原鈣粘著蛋白pc5的多核苷酸序列。
4.根據(jù)權(quán)利要求1、2或3的多核苷酸序列,其為DNA序列。
5.根據(jù)權(quán)利要求4的DNA序列,其為cDNA序列。
6.根據(jù)權(quán)利要求4的DNA序列,其為基因組DNA序列。
7.根據(jù)權(quán)利要求4的DNA序列,其為完全或部分地化學(xué)合成的DNA序列。
8.根據(jù)權(quán)利要求1的多核苷酸序列,其包含SEQ ID NO109的人原鈣粘著蛋白pc3編碼序列。
9.根據(jù)權(quán)利要求2的多核苷酸序列,其包括SEQ ID NO111的人原鈣粘著蛋白pc4編碼序列。
10.根據(jù)權(quán)利要求3的多核苷酸序列,其包括SEQ ID NO114的大鼠原鈣粘著蛋白pc5編碼序列。
11.包含根據(jù)權(quán)利要求4之DNA序列的生物學(xué)功能性DNA載體。
12.根據(jù)權(quán)利要求11的載體,其中所說的DNA序列可操作地連接到表達(dá)控制DNA序列上。
13.以允許在所說的宿主細(xì)胞中表達(dá)原鈣粘著蛋白多肽的方式用根據(jù)權(quán)利要求4的DNA序列轉(zhuǎn)化或轉(zhuǎn)染的宿主細(xì)胞。
14.生產(chǎn)原鈣粘著蛋白多肽的方法,其包括在適當(dāng)?shù)臓I養(yǎng)培養(yǎng)基中培養(yǎng)根據(jù)權(quán)利要求13的宿主細(xì)胞以及從所說的細(xì)胞中或從其賴以生長(zhǎng)的培養(yǎng)基中分離原鈣粘著蛋白多肽。
15.純化并分離的人原鈣粘著蛋白pc3多肽。
16.純化并分離的人原鈣粘著蛋白pc4多肽。
17.純化并分離的大鼠原鈣粘著蛋白pc5多肽。
18.對(duì)人原鈣粘著蛋白pc3特異的抗體物質(zhì)。
19.對(duì)人原鈣粘著蛋白pc4特異的抗體物質(zhì)。
20.對(duì)大鼠原鈣粘著蛋白pc5特異的抗體物質(zhì)。
21.根據(jù)權(quán)利要求18、19或20的抗體物質(zhì),其為單克隆抗體。
22.產(chǎn)生根據(jù)權(quán)利要求21的單克隆抗體的雜交瘤細(xì)胞系。
23.調(diào)節(jié)人原鈣粘著蛋白pc3的結(jié)合活性的方法,其包括使所說的原鈣粘著蛋白與根據(jù)權(quán)利要求18的對(duì)所說的原鈣粘著蛋白特異的抗體物質(zhì)接觸。
24.調(diào)節(jié)人原鈣粘著蛋白pc3的結(jié)合活性的方法,其包括使所說的原鈣粘著蛋白與所說原鈣粘著蛋白的肽配體接觸。
25.調(diào)節(jié)人原鈣粘著蛋白pc4的結(jié)合活性的方法,其包括使所說的原鈣粘著蛋白與根據(jù)權(quán)利要求19的對(duì)所說的原鈣粘著蛋白特異的抗體物質(zhì)接觸。
26.調(diào)節(jié)人原鈣粘著蛋白pc4的結(jié)合活性的方法,其包括使所說的原鈣粘著蛋白與所說原鈣粘著蛋白的肽配體接觸。
27.調(diào)節(jié)大鼠原鈣粘著蛋白pc5的結(jié)合活性的方法,其包括使所說的原鈣粘著蛋白與根據(jù)權(quán)利要求20對(duì)所說的原鈣粘著蛋白特異的抗體物質(zhì)接觸。
28.調(diào)節(jié)大鼠原鈣粘著蛋白pc5的結(jié)合活性的方法,其包括使所說的原鈣粘著蛋白與所說原鈣粘著蛋白的肽配體接觸。
全文摘要
本發(fā)明提供了編碼稱為原鈣粘著蛋白的鈣粘著蛋白樣多肽的多核苷酸序列及其變異體,并提供了重組生產(chǎn)它們的方法和材料。本發(fā)明還公開了對(duì)原鈣粘著蛋白特異的抗體物質(zhì),這些抗體物質(zhì)可用于調(diào)節(jié)原鈣粘著蛋白的天然結(jié)合和/或調(diào)節(jié)活性。
文檔編號(hào)C07K16/00GK1134172SQ95190790
公開日1996年10月23日 申請(qǐng)日期1995年6月26日 優(yōu)先權(quán)日1994年6月27日
發(fā)明者S·鈴木 申請(qǐng)人:多亨尼眼科研究院