專利名稱：細胞周期關卡與pik相關的激酶材料和方法
技術領域：
本發明廣泛涉及編碼細胞周期關卡有關磷脂酰肌醇激酶(PIK)的基因以及細胞中對DNA損傷反應必需的蛋白。關卡激酶在監督由于復制錯誤、DNA錯配、輻射處理或化療藥物而發生的DNA損傷中起作用。這些激酶在DNA損傷后導致細胞周期停滯的調節通路中，在DNA復制開始前給細胞通知和時間以修復損傷方面是必需的。更特別地，本發明涉及一種新的人與PIK相關的激酶，哺乳動物細胞周期監督1(MCCS1)，編碼PIK相關激酶的多核苷酸以及測定和調節該激酶和相關激酶酶活的方法。
背景真核細胞生長和分裂的過程是由G1期、S期、G2期和M期四個時相組成的體細胞或有絲分裂細胞周期。G1，S，和G2期統稱為細胞周期和分裂間期。在所有真核細胞種類中，細胞周期在其基本過程和調節方式上是結構和功能保守的。在G1(間)期，細胞的生物合成活性高速進展。當DNA合成開始時S(合成)期開始，在細胞核的DNA含量得到復制并形成相同的兩套染色體時S期結束。細胞然后進入G2(間)期直至有絲分裂開始。在有絲分裂中，染色體配對、分離并形成兩個新核，在胞質分裂時細胞本身分成兩個子細胞，每個子細胞得到含有兩套染色體中之一的一個核。有絲分裂和胞質分裂共同形成細胞周期的M(有絲分裂)期。胞質分裂結束M期并標志下一個細胞周期分裂間期的開始。細胞周期中事件進行的程序是嚴密調控的，一個細胞周期事件的開始依賴于前一個細胞周期事件的完成。這使細胞從一代到下一代遺傳物質的復制和分離保持忠實性。
術語“細胞周期關卡”指細胞復制過程中使不連續事件結合起來的蛋白、信號、步驟和反饋控制，使得在細胞周期中保持基本的依賴性。本發明特別涉及確保有絲分裂延遲直至DNA合成完成和/或DNA損傷的準確修復出現的細胞周期關卡。
細胞周期關卡的失效使個體傾向于或直接導致許多疾病狀態如癌癥，運動失調性毛細血管擴張癥，胚胎畸形以及多種與異常B和T細胞生成相關的免疫缺陷。后者與病理狀態如狼瘡，關節炎和自身免疫疾病有關。因此深入的研究著力集中在識別細胞周期關卡和關卡功能所必需的蛋白。
對酵母菌pombe裂殖酵母和釀酒酵母的基因分析已鑒定了幾種響應離子化輻射(IR)的細胞周期停滯和DNA修復重要的基因。綜述見Carr和Hoekstra，Trends in Cell Biology.532-40(1995)。在兩種酵母中均鑒定的一種這類基因是細胞周期停滯在G2期的DNA損傷關卡和監控DNA合成的完成并將細胞周期停滯在S期的相關關卡。該基因在pombe裂殖酵母[Seaton et al.，Gene，11983-89(1992)]中命名為rad3+，在啤酒酵母中命名為MECI/ESR1[Kato et al.，Nuc.Acids.Res.，22(15)3104-3112(1994)]，此后稱做rad3+。具有rak3+突變的細胞不能覺察或對DNA損傷有適當的反應，因而暴露于斷裂劑或事件(如IR，DNA損傷劑和影響染色體完整的突變)后比野生型細胞更快地喪失生存能力。見Weinert等，GENES & DEVELOPMENT，8652-665(1994)和Al-Khodairy等，EMBO J.，11(4)1343-1350(1992)。對IR的敏感性(放射敏感性)可通過關卡反應或直接DNA修復反應的缺陷而引起。
rad3+基因的產物是一個約270KD的蛋白，歸于一個正在壯大的高分子量PIK相關激酶的家族。見Hunter，Cell，831-4(1995)討論了該激酶家族。此基因家族成員中發現的催化區域一級結構與已詳細表征的磷脂酰肌醇激酶緊密相關。此結構關系最初暗示這些PIK相關激酶可能能磷酸化脂質。但當檢測PIK相關激酶底物專一性時，這些酶顯示蛋白激酶的作用并已證明磷酸化磷脂酰肌醇。Hartley等，Cell，82849-856(1995)，報道純化的樣品在蛋白激酶試驗中十分有活性，而不顯示脂質激酶活性。鑒定的其它PIK相關激酶包括釀酒酵母的TEL1基因產物，它影響端粒長度[Greenwell等，Cell82823-829(1995)]，melanogaster果蠅的Mei 41+基因產物，它對G2關卡和減數分裂進行十分重要[Hari等，Cell82815-821(1995)]，小鼠的DNA-PK基因產物，它在免疫球蛋白重排和DNA雙鏈斷裂的加工中是重要的，還有在G1/S過渡中重要的FRAP基因產物[Brown，E.等，Nature，377441-446(1995)]。DNA-PK基因的突變會導致嚴重的復合免疫缺陷綜合癥(SCID)缺陷(Hartley et al.，同上)。
人類關卡功能所需的分子成分鮮為人知。通過分析人疾病綜合癥共濟失調伴毛細血管擴張癥(AT)已經識別了哺乳動物關卡機制的必需的一種分子成分。AT病人顯示多種臨床癥狀，包括對多種腫瘤的易感性。AT病人的成纖維細胞是輻射敏感的，并在IR處理后，不能產生細胞周期停滯，導致抗放射DNA合成現象。這使人聯想起pombe裂殖酵母rad3缺陷，這樣的細胞不能對DNA損傷適當地覺察或反應。有趣的是負責AT的基因座運動失調性毛細血管擴張癥突變(ATM)基因最近在Savitsky等，Science，2681749-1753(1995)中描述，并且部分cDNA編碼具有與rads+基因相似氨基酸的蛋白。Savitsky et al.，HumanMolecular Genetics，4(11)2025-2032(1995)描述編碼全長ATM的cDNA的分離。rad3+酵母突變株和喪失有功能的ATM的哺乳動物細胞的放射敏感性增加提示這些蛋白可能包含關卡蛋白家族。
Kuerbitz等，Proc.Natl.Acad.Sci.USA，897492-7495(1992)證實抑癌基因p53是G1關卡和DNA損傷后觀察到的細胞周期停滯需要的。照射細胞導致p53水平增加，使p53應答基因轉錄活化。一種p53誘導的靶點是WAF1基因產物(也叫P21，CIPl和sdil)。WAF1是叫做細胞周期蛋白依賴性激酶抑制蛋白的一類擴展之中的細胞周期調節物的一個成員。細胞周期蛋白依賴性激酶的活性控制細胞周期的運轉。因而WAF1的轉錄活性在依賴于DNA損傷的p53的誘導和對細胞周期演進必需的激酶的抑制作用之間提供了直接的聯系。見Elledge和Harper，CurrentOpinion in Cell Biology，6847-852(1994)。p53基因的突變是人類癌癥中最常見的基因變化。例如，Baker等，Science，244217-221(1989)報道大約70％人結腸癌含有p53基因的缺失或突變拷貝。此外，Fearon等，Cell，61759-767(1990)報道乳腺癌、肺癌、膀胱癌和腦癌與p53基因所在的染色體17p區域的丟失有關。
目前，對哺乳動物細胞中G2關卡的分子成分相對知之甚少。咖啡因是一種取消G2關卡控制的化學實體。Russell等，Cancer Res.，551639-1642(1995)和Powell等，Cancer Res.，551643-1648(1995)報道其區別僅在于有或無有功能的p53存在的細胞系分析證明在那些缺少依賴于p53的G1關卡的細胞中，對IR有優先咖啡因增強的敏感性。因而，與含有完整G1關卡的細胞相比，缺乏G1和G2關卡的細胞中，潛在致死損傷到致死損傷的轉變更多。
當某些細胞遭受依賴于DNA損傷的細胞周期停滯時，其它細胞似乎通過啟動一種叫做細胞凋亡或程序性細胞死亡的內在自殺程序對DNA損傷起反應。決定哪種過程發生的因素不完全清楚。最近的工作證明p53在G1細胞周期過渡的調節和細胞凋亡中均起重要作用。Symonds等Cell，78703-711(1994)描述了作為抑制體內腫瘤生長和演進的依賴于p53的細胞凋亡。
高劑量的放射和化療用于治療腫瘤細胞以嚴重地損傷DNA致使細胞死亡。然而，即使具有p53基因突變的腫瘤細胞在G1關卡是缺損的，它們仍可修復放射或化療引起的DNA損傷。本發明預期比如腫瘤細胞中G2關卡的抑制作用可能導致一種狀態，在此狀態中腫瘤細胞不能修復DNA損傷，因此使腫瘤細胞對DNA損傷劑敏感。含有完整G1和G2關卡的正常細胞在G2關卡特異性抑制劑存在下仍能修復DNA損傷。因而，先用G2關卡特異性抑制劑再用放射或化療治療腫瘤會增加細胞殺傷效果，從而減少所需的毒性DNA—損傷劑的劑量。
因此本領域存在鑒別參與細胞周期關卡的哺乳動物蛋白以開發與缺陷細胞周期關卡相關的人類疾病狀態的療法，并分離編碼這些蛋白的基因的需要，它們可能對治療有用或能開發治療上有用的這些基因編碼蛋白的調制劑。
發明概述本發明提供對細胞周期關卡必需的新人類PIK相關激酶，它在細胞周期的G2期對損傷的和非復制的DNA都有反應。
一方面，本發明提供編碼細胞周期關卡PIK相關激酶MCCS1的純化并分離的多核苷酸(如DNAs和RNAs，其編碼鏈和非編碼鏈)，以及編碼其它細胞周期關卡PIK相關激酶的多核苷酸，這些多核苷酸與編碼MCCS1激酶結構域的MCCS1多核苷酸區域表現出約50％、60％或65％的核苷酸一致性(SEQ ID NO30的MCCS1α核苷酸6579-7562，SEQ ID NO32的MCCS1β核苷酸6457-7440)。換句話說，MCCS1樣PIK相關激酶與MCCS1激酶結構域(SEQ ID NO31的MCCS1α氨基酸2083-2410，或SEQ ID NO33的MCCS1β氨基酸2152-2480)顯示了40％，45％或50％氨基酸一致性。本發明預期的多核苷酸包括基因組DNAs，RNAs，cDNAs和完全或部分化學合成的DNAs。本發明優選的多核苷酸包含在SEQ ID NO30列出的MCCS1αDNA序列，SEQ ID NO3列出的部分MCCS1βDNA序列，SEQ ID NO32列出的全長MCCS1βDNA序列和在嚴格條件下可與其非編碼鏈雜交的或假如沒有基因冗余，可與其非編碼鏈雜交的DNA序列。典型的嚴格雜交條件如下在3×SSC，20mM NaPO4pH6.8中于65℃雜交，并在65℃用0.2×SSC洗。本領域技術人員已知這些條件的變化根據欲雜交序列的長度和GC核苷酸堿基含量而定。本領域的配方標準適合確定準確的雜交條件。見Sambrook et al.，9.47-9.51，分子克隆，冷泉港實驗室出版，冷泉港，紐約(1989)。SEQ ID NO30的MCCS1αDNA保藏在美國典型培養物保藏中心(ATCC)，12301 Parklawn Drive，Rockville，Maryland 20852，1995年11月3日，作為大腸桿菌DH5α的質粒pBSHFB/HT2-27插入片段被指定ATCC登記號No 69951。SEQ ID NO32的MCCS1βDNA作為大腸桿菌中517質粒的插入片段于1995年11月7日保藏于ATCC，指定ATCC登記號No 69950。
本發明提供的DNA序列信息使通過已知技術如上述DNA/DNA雜交和聚合酶鏈反應(PCR)克隆，分離和鑒定編碼相關分子的DNAs成為可能。作為一系列實施例，知道編碼MCCS1的cDNA序列使得有可能通過編碼該激酶的基因組DNA序列的DNA/DNA雜交分離和表達調控序列，如啟動子，操縱子等。相似地，知道編碼MCCS1β的部分cDNA序列便可能分離完整的cDNA。在嚴格條件下用本發明DNA序列進行的DNA/DNA雜交步驟同樣期望使編碼PIK相關激酶等位變種DNA分離；與PIK相關激酶同源的非人種的酶；以及其它具有一種或多種酶活性，或具有與MCCS1參加的細胞周期關卡通路中的成員或調節物相互作用能力的其它結構上相關的蛋白。本發明的多核苷酸當可檢測標記后還可用于雜交試驗以檢測細胞合成MCCS1的能力。本發明提供的DNA序列信息還可通過同源重組或“剔除”策略[見Capecchi，Science，2441288-1292(1989)]使不能表達功能MCCS1或表達MCCS1變異體的嚙齒動物的發育成為可能。這種嚙齒動物作為體內研究MCCS1活性和MCCS1調制劑的模型是有用的。本發明的多核苷酸也許是對識別構成疾病狀態基礎的MCCS1基因座中基因變化有用的診斷方法基礎。通過本發明還可得到通過那些通常表達同一基因的細胞調節的MCCS1表達的有關反義多核苷酸。
本發明也提供自主復制重組體構建物，如參入本發明多核苷酸的質粒和病毒DNA載體，特別是其中多核苷酸功能性與內源或異源表達控制DNA序列和轉錄終止子連接的載體。
根據本發明的另一方面，宿主細胞特別是單細胞的宿主細胞如原核和真核細胞，用本發明的DNAs以允許PIK相關激酶在此表達的方式被穩定轉化或轉染。本發明宿主細胞在MCCS1大規模生產的方法中十分有用，其中細胞生長于合適的培養基中，目的酶從細胞中或細胞所生長的培養基中分離。
仔細考慮了SEQ ID NO31，SEQ ID NO4或SEQ ID NO33中列出的部分或全部氨基酸序列的MCCS1產物。使用哺乳動物宿主細胞期望提供這些翻譯后修飾(豆蔻酰化，糖基化，截短，脂質化和酪氨酸、絲氨酸或蘇氨酸磷酸化)，因為可能是賦予本發明重組表達產物最佳生物活性所必需的。本發明的酶產物可以是全長多肽，片段或變體。變體包括MCCS1產物，其中一個或多個指定的(即天然編碼的)氨基酸被缺失或替換，或其中加入一個或多個非指定氨基酸(1)不喪失對MCCS1特異的激酶活性；或(2)失去對MCCS1特異的激酶活性；或(3)失去與細胞周期關卡通路的成員或調節物相互作用的能力。MCCS1底物和與MCCS1相互作用的蛋白可用不同方法鑒別。
MCCS1的底物可通過在激酶活性試驗中參入試驗化合物而鑒定。MCCS1激酶懸于激酶緩沖液，在試驗化合物(如酪蛋白，組蛋白H1或合適的底物肽)存在或不存在情況下溫孵。通過放射自顯影或液閃計數法測量由激酶轉移到試驗化合物上的磷酸摩爾數。將磷酸轉移到試驗化合物上表明試驗化合物是激酶的底物。
相互作用蛋白可通過下列試驗鑒定。
本發明預期的第一個試驗是雙雜交篩選。雙雜交系統在酵母中建立[Chien等，Proc.Natl.Acad.Sci.USA，889578-9582(1991)]并基于激活報告基因的轉錄因子在體內的功能重建。特別地，編碼與MCCS1相互作用的蛋白的多核苷酸通過如下分離用含有處于在啟動子的控制下報告基因的DNA構建物轉化或轉染合適的宿主細胞，該啟動子受具有DNA結合結構域和活化結構域的轉錄因子調節；在宿主細胞中表達編碼部分或全部MCCS1與轉錄因子DNA結合結構域或活化結構域第一次融合物的第一個雜種DNA序列；在宿主細胞中表達編碼部分或全部推定MCCS1結合蛋白與未參入第一次融合物的轉錄因子的DNA結合域或活化結構域第二次融合物的第二個雜種DNA序列文庫；通過檢測宿主細胞中報告基因產物的產生，而檢測特定宿主細胞中MCCS1相互作用蛋白與MCCS1的結合；并從特定宿主細胞中分離編碼相互作用蛋白的第二個雜交DNA序列。當前優選用于試驗的是驅動報告基因表達的lexA啟動子，lacZ報告基因是包含lexA DNA結合域和GAL4活性轉換結構域的轉錄因子，和酵母宿主細胞。
鑒定與MCCS1相互作用蛋白的其它方法包含固定 MCCS1或一種試驗蛋白，可監測地標記非固定化 結合伙伴，將結合伙伴一起溫育并測定結合標記的量。結合標記指示試驗蛋白與MCCS1的相互作用。
另一種確定MCCS1相互作用蛋白的方法包括在涂有(或浸漬)熒光劑的固體支持物上固定化MCCS1或其片段，用能激發熒光劑的化合物標記試驗蛋白，將標記的試驗蛋白與固定化的MCCS1接觸，檢測熒光劑的光發射，并鑒定作為導致熒光劑發光的試驗蛋白的相互作用蛋白。或者，在試驗中可固定化推定的相互作用蛋白并標記MCCS1。
本發明還包含抗體產物(如單克隆和多克隆抗體，單鏈抗體，嵌合抗體，嫁接CDR的抗體等)及其它對本發明MCCS1激酶特異的結合蛋白(如上面試驗中確定的)。結合蛋白可用分離的天然或重組酶發生。反過來，結合蛋白對純化重組體和天然產生的酶以及鑒定產生這種酶的細胞有用。本發明特別說明的單克隆抗體是由雜交瘤細胞系224C和224F產生的單克隆抗體，于1996年11月7日保藏于美國典型培養物保藏中心(ATCC)，12301 Parklawn Drive，Rockville，MD 20852并分別指定ATCC登記號Nos HB 12233和HB 12234。檢測和定量細胞及流體中蛋白的方法可包含“三明治”方法形式中的單個或多種抗體物質。結合蛋白在調制(即封閉，抑制或刺激)酶/底物或酶/調制劑相互作用中也是明顯有用的。對PIK相關激酶結合蛋白特異的抗獨特型抗體也在考慮之中。
本發明考慮到MCCS1基因中的突變，它導致MCCS1基因產物正常功能的喪失，構成無G2細胞周期關卡參與的人疾病狀態的基礎。恢復MCCS1活性的基因療法因而可能在治療那些疾病中(如睪丸癌)指出。有功能的MCCS1基因向合適細胞的轉運在體內或來自體內使用病毒載體(如腺病毒，相關腺病毒或逆轉錄病毒)或來自體內采用物理的DNA轉移方法(如質脂體或化學處理)實現。基因治療技術的敘述見Friedmann，Science，2441275-1281(1989)；Verma，Scientific；American68-84(1990)；Miller，Nature，35)455-460(1992)。換句話說，可以預期在其它人類疾病中阻礙MCCS1表達或抑制MCCS1活性的，對治療疾病將是有用的。預期反義療法或基因療法可能用于MCCS1表達的負調節。能特異地與MCCS1表達控制序列或MCCS1 RNA結合的反義核酸(優選10-20堿基對寡核苷酸)被導入細胞(如通過病毒載體或例如質脂體的膠體分散系統)。反義核酸與細胞中MCCS1靶序列結合并阻止靶序列的轉錄或翻譯。硫化磷的酯和甲基磷酸酯反義寡核苷酸被本發明特別期望于治療使用。反義寡核苷酸可在其5′端再被多聚L-賴氨酸，轉鐵蛋白多聚賴氨酸或膽固醇部分修飾。
再者，假如MCCS1基因之外如p53基因的基因突變導致一種特殊的癌癥形式，那么抑制MCCS1的轉錄或酶活及G2細胞周期關卡的試劑可用于使癌細胞對化療或放療更敏感。這種試劑的治療價值基于這樣一個事實，即目前的放療或化療在大多數情況下不能克服p53突變癌細胞來覺察和修正作為治療結果的DNA損傷的能力。因而腫瘤細胞可簡單地修復DNA損傷。所以本發明的調制劑可做為化療、放療的佐劑，或基本上直接作為化療藥。
調制MCCS1激酶活性的試劑可通過將試驗化合物與從天然表達PIK相關激酶的細胞中免疫純化的MCCS1，與表達該酶的重組原核或真核宿主細胞中得到的MCCS1或與純化的MCCS1溫育，然后測量被試化合物對MCCS1活性的影響來鑒定。PIK相關激酶的活性可通過測定該激酶從γ-32P-ATP向其本身(自身磷酸化)或外源性物質如脂質或蛋白轉移32P-磷酸鹽的摩爾數來測量。參入底物中磷酸鹽的量通過液閃計數或放射自顯影測定。被試化合物存在比不存在情況下向底物轉移的磷酸鹽的摩爾數增加表示該被試化合物為所述MCCS1激酶的激活劑。相反地，被試化合物存在比不存在情況下向底物轉移的磷酸鹽的摩爾數減少表示該調制劑為所述MCCS1激酶的抑制劑。另一方面，還期望了調節MCCS1和ATM或其中之一的試劑。調制MCCS1的試劑在上述ATM為進行磷酸化酶的激酶試驗中篩選。
在當前的優選試驗中，聯接到瓊脂糖珠的MCCS1特異抗體與從表達此激酶的宿主細胞制備的細胞裂解物溫育。珠子洗去非特異結合的蛋白，再重懸于激酶緩沖液中。加Aγ-32P-ATP和合適的外源性底物如脂質或肽啟動反應。激酶活性通過測定轉移到激酶本身或加入底物的32P-磷酸鹽的摩爾數測得。在優選的實施方案中，宿主細胞缺乏內源性MCCS1和/或ATM激酶活性。化合物調制MCCS1激酶活性的選擇性可通過比較其對MCCS1及對其它已知PIK相關激酶的活性來評價。本發明的重組MCCS1產物與其它重組PIK相關激酶產物在一系列獨立的試驗中的組合提供了一個和開發選擇性MCCS1調制劑的系統。
而且，組合文庫、肽和肽模擬物、確定的化學實物、寡核苷酸和天然產物文庫可用下面所述的實驗篩選作為調制劑的活性。
例如，鑒定MCCS1激酶活性的調制劑的試驗包括將激酶緩沖液中的MCCS1激酶樣品與γ-32P-ATP和外源性激酶底物，有或沒有被試化合物存在下一起溫育，并測量轉到底物上的磷酸鹽摩爾數。被試化合物存在比不存在情況下轉移到底物上的磷酸鹽摩爾數增多，表示被試化合物為所述MCCS1激酶的激活劑。反之，被試化合物存在比不存在情況下轉移到底物上的磷酸鹽摩爾數減少，表示該調制劑為所述MCCS1激酶的抑制劑。
再者，鑒定調制MCCS1與其它蛋白相互作用的化合物的方法可包括用包含在啟動子控制之下的報告基因的DNA構建物轉化或轉染合適的宿主細胞，該啟動子受具有DNA結合域和活化域的轉錄因子調節；在宿主細胞中表達編碼部分或全部MCCS1與轉錄因子DNA結合域或活化域第一次融合物的第一個雜種DNA序列；在宿主細胞中表達編碼部分或全部與MCCS1相互作用蛋白和未參入第一次融合物的轉錄因子的DNA結合域或活化域的第二個雜種DNA序列；在有或沒有被試化合物存在下，通過測定宿主細胞中報告基因產物的產量檢測在特定宿主細胞中相互作用蛋白與MCCS1的結合，從而評價被試化合物對MCCS1和相互作用蛋白間相互作用的影響；并鑒定與無調控化合物時報告基因產物的產量相比改變了報告基因產物產量的被試化合物作為調控化合物。當前優選用于試驗的是驅動報告基因表達的lexA啟動子，lacZ報告基因，包含lexADNA結合域和GAL4反式激活結構域的轉錄因子，和酵母宿主細胞。
鑒定調制MCCS1和一種相互作用蛋白間相互作用的化合物的另一種方法包括固定化化MCCS1或一種天然MCCS1相互作用蛋白，可檢測地標記未固定化的結合伙伴，將結合伙伴共同溫育并測定被試化合物對標記結合量的影響，其中被試化合物存在比不存在情況下標記結合量減少表示被試化合物為MCCS1與蛋白相互作用的抑制劑。反之，被試化合物存在比不存在情況下標記結合量增加表示此推定調制劑為MCCS1與蛋白相互作用的激活劑。
本發明預期的鑒定調節MCCS1和一種相互作用蛋白間結合的化合物的另一種方法包括在涂布(或浸漬)熒光劑的固體支持物上固定化MCCS1或其片段，用能激發熒光劑的化合物標記相互作用蛋白，將固定化的MCCS1與標記的相互作用蛋白在有或無被試化合物存在下相接觸，檢測熒光劑的光發射，并鑒定與無被試化合物存在下相比影響熒光劑光發射的那些被試化合物作為調制化合物。或者，在試驗中可固定化MCCS1相互作用蛋白并標記MCCS1。
本發明還提供用于鑒定調制MCCS1或ATM活性的化合物的基于細胞的互補實驗。該方法包括與細胞中基因改變有關的表型特征的互補。例如，esrl-1基因改變導致酵母細胞對DNA損傷的細胞敏感性[Kato等，Nuc.Acids.Res.，22(15)3104-3112(1994)]。esrl-1細胞在用DNA損傷劑如離子化輻射或斷裂劑處理后不能對DNA損傷覺察或適當地反應，基因改變細胞的表型特征通過在細胞中轉化和表達MCCS1或ATM被互補。有或無被試化合物存在下轉化的細胞用DNA損傷處理(如離子化輻射)并測量細胞對DNA損傷的敏感性。影響細胞對MCCS1和/或ATM的DNA損傷活性敏感性的試劑定為調制劑。
MCCS1的調制劑可能會影響其激酶活性、細胞中定位和/或其與細胞周期關卡通路成員的相互作用。MCCS1調制劑可配制于含有藥用載體的組合物中。這種組合物還可包括化療劑。指示劑量對體內MCCS1活性的調制會是足夠的。選擇的調制劑可包括如特異性與MCCS1或MCCS1核酸結合的多肽或肽，特異性與PIK相關激酶或PIK相關激酶核酸結合的寡核苷酸，和/或其它特異地與MCCS1或MCCS1核酸反應的非肽化合物(如分離或合成的有機分子)。本發明還期望影響野生型MCCS1酶活或細胞定位的MCCS1突變形式。目前優選的開發選擇性調制劑的靶點的PIK相關激酶區域包括比如下面四個區域MCCS1α氨基末端效應物結構域(SEQ ID NO31的1-1081氨基酸)，MCCS1β氨基末端效應物結構域(SEQ ID NO＝33的1-1150氨基酸)，MCCS1αrad3+結構域(SEQ ID NO＝31的1082-2082氨基酸)，MCCS1βrad3+結構域(SEQ ID NO＝33的1151-2151氨基酸)，MCCS1αPIK結構域(SEQ ID NO＝31的2083-2410氨基酸)，和MCCS1βPIK結構域(SEQ ID NO＝33的2152-2480氨基酸)。
詳細描述本發明由以下實施例來解釋。實施例1詳述編碼MCCS1激酶cDNAs的分離。實施例2描述了人MCCS1基因在人染色體3的定位。MCCS1基因在大腸桿菌和昆蟲細胞的重組表達分別在實施例3和4中描述。實施例4也介紹測定MCCS1激酶活性的試驗。實施例5描述MCCS1-特異的多克隆和單克隆抗體的產生。實施例6報道來自小鼠睪丸的MCCS1激酶相關活性的免疫沉淀。實施例7檢查MCCS1 mRNA在各種人組織和癌細胞株的表達。實施例8描述MCCS1 mRNA的分析和在小鼠睪丸中的蛋白表達。實施例9描述減數分裂細胞中MCCS1蛋白表達的分析。底物和MCCS1相互作用蛋白的測試在實施例10描述。實施例11描述調制劑和MCCS1激酶活性調制劑的測試。實施例12描述用于確定MCCS1和/或ATM調制劑的基于細胞的互補試驗，以及實施例13描述ATM的激酶活性。
實施例1編碼與PIK相關激酶MCCS1的cDNA通過系列PCR反應分離。
S.pombe rad3+(Hari等，見上)和釀酒酵母MEC1(Kato等，見上)的氨基酸序列的排列是七個簡并性寡核苷酸的設計基礎，該寡核苷酸在序列間編碼(或互補于)最高同源性/最低簡并性的區域并含有方便的剪切位點以便于擴增產物的克隆。然后寡核苷酸被用于基于PCR的試驗中以分離相關的人序列。
開始，PCR擴增在從大鼠T-細胞的cDNA制品，人外周血單核細胞(PBMC)，以及釀酒酵母基因組DNA上進行。用五對寡核苷酸(oDH15a/oDH16，oDH15b/oDH16，oDH17a/oDH16，oDH15a/oDH17b，和oDH15b/oDH17b)進行初步擴增。寡核苷酸引物序列包括肌苷，并對簡并的核苷酸位置以IUPAC命名列如下。
oDH15a(SEQ ID NO5)5′GCA GAC GGA TCC GGI WCI GAY GGI AAY HTI TAY 3′
oDH15b(SEQ ID NO6)5′GCA GAC GGA TCC GGI WCI GAY GGI AAY 3′oDH16(SEQ ID NO7)5′GCA GAC GAA TTC RCA RTY RAA RTC IAC RTG 3′oDH17a(SEQ ID NO8)5′GCA GAC GGA TCC AAR TTYCCI CCI RTI YTI TAY SAR TGG TT3′oDH17b(SEQ ID NO9)5′GCA GAC GAA TCC AAC CAYTSR TAI ARI AYI GGI GGR AAY TT 3′PCR在1×PCR緩沖液(Perkin Elmer Cetus，Emeryville，California)，2-3μMoDH引物，1.5mM MgCl2，200μMdNTPs，和0.5μlAmpli標記聚合酶的混合物中進行。反應在Perkin-Elmer Cetus Thermocycler480型儀器上完成，條件如下在94℃變性1分鐘，在64℃退火2分鐘，并于72℃延長1分鐘進行三次循環。再用60℃退火溫度循環三次，56℃退火循環三次，并以94℃變性1分鐘，54℃退火2分鐘和72℃延長1分鐘進行30個循環結束。PCR產物在2或4％Tris乙酸EDTA(TAE)瓊脂糖凝膠上分離，用溴化乙錠染色，通過UV熒光觀察DNA產物。
從酵母基因組DNA，大鼠T-細胞cDNA，和人PBMC cDNA的初步擴增中，僅用酵母基因組DNA(oDH17a/oDH16)的單個反應給出可見的擴增產物，得到具有釀酒酵母MEC1區域的期望大小的在這些引物間的產物。因此完成了利用大鼠T-細胞和PBMC cDNA的oDH17a/oDH16擴增的進一步分析。為了除去寡核苷酸和可能干擾隨后的PCR的“引物二聚體”，在再次PCR前純化初步的反應。
采用“嵌套”PCR方法，擴增用引物對oDH18a/oDH16和oDH18b/oDH16在前述反應條件下以94℃變性1分鐘，55℃退火1分鐘和72℃延長30秒的循環重復30次。oDH18a和oDH18b寡核苷酸引物的序列包括肌苷，并對簡并的核苷酸位置以IUPAC命名列如下。
oDH18a(SEQ ID NO10)5′GCA GAC GGA TCC YTI GGI YTI GGI GAY CGI CA 3′oDH18b(SEQ ID NO11)5′GCA GAC GGA TCC YTI GGI YTI GGI GAY AGR CA 3′在酵母基因組和人PBMC cDNA初步反應的再次擴增中可見大約90堿基對(bp)的產物(對這些引物期望大小的擴增產物)。在大鼠T-細胞cDNA初步反應的再次擴增中未見90bp產物，此反應不進一步分析。
除了大約90bp產物，也產生幾個其它非特異帶，盡管比初步反應用oDH17a/oDH16再次擴增時觀察到的明顯較少。在酵母基因組DNA初步反應的oDH18a/oDH16和oDH18b/oDH16再次擴增中出現了大約90bp產物，在人PBMC cDNA初步反應的再次擴增過程中僅oDH18a/oDH16反應產生了適當大小的片斷。推測這反應了在人基因(比較引物oDH18a和oDH18b)中密碼子的使用。來自人PMBC cDNA初步反應的oDH18a/oDH16再次擴增的大約90bp產物用膠純化并亞克隆到pBluescript SKII+克隆載體(Stra標記ene，La Jolla，California)并測序。
被90bp產物編碼序列的分析表明推斷的氨基酸序列與釀酒酵母MEC1和S.pombe rad3+相似，但相互不是相同的。為了確定編碼序列的較大區域和擴大序列比較，合成了一個非簡并寡核苷酸，oDH23 5’GACGCAGAATTCACCAGTCAAAGAATCAAAGAG 3’(SEQ ID NO12)，用于附加的擴增反應。用oDH17a/oDH23對純化的PBMC cDNA初步反應的再次擴增導致一個174bp擴增產物的產生。該片斷然后被純化，亞克隆并如上所述測序。概念翻譯產物的計算機分析確定其與MEC1和rad3+的關系(相似但不相同)。該PCR片斷然后被用作探針來篩選含有巨噬細胞cDNA的質粒文庫，采用的雜交條件如下硝基纖維素膜用放射性標記的探針在3×SSC，5×Denhardt’s，0.1％十二烷基肌氨酸鈉，20mM NaPO4pH6.8，100μg/ml單鏈鮭精DNA中于65℃溫育18到24小時。在0.2×SSC，0.1％SDS中于65℃30分鐘洗3次(更換洗滌緩沖液)。分離出四個陽性克隆，測定了每一個的核苷酸序列。四個序列的計算機分析證明它們是源自與來自S.pombe的rad3+基因同源的基因座的重疊克隆。克隆517(ATCC 69950)含有2.8kbp的插入并且其DNA和推斷的氨基酸序列分別列于SEQ ID NOs3和4。此克隆包含編碼氨基末端截短的870個氨基酸蛋白產物的讀碼框，該蛋白產物與rad3+的羧基端有39％相同。cDNA插入的蛋白產物被命名為MCCS1β。
克隆517的序列被用于設計寡核苷酸mo3 5’-CTACAGAGCCAAGGAG-3’(SEQ ID NO13)和mo6 5’-TCGAGCTATGCTAGTTGGGC-3’(SEQ ID NO14)，采用來自克隆517的膠純化的EcoRI片斷做為模板此寡核苷酸被用來產生探針。PCR條件如下50ng DNA片斷，1×PCR緩沖液(Perkin-Elmer Cetus)，1.5mM MgCl2，200μM dATP，dGTP，和TTP，1μMdCTP，50μCiα32P-dCTP，每種寡核苷酸10ng/ml，1U AmpliTaq(Perkin-Elmer Cetus)。反應在480型Perkin-Elmer Cetus Thermocycler上進行，在94℃首次變性循環4分鐘，隨后是94℃15秒，60℃15秒，72℃30秒的20次循環。未摻入的核苷酸用Stra標記ene Nuc-trap Push柱除去。
由于Northern印記分析顯示對應于克隆517mRNA的表達在睪丸最高，用產生自PCR的探針從人睪丸cDNA文庫(Stra標記ene#939202)中篩選了一百萬克隆并獲得十一個克隆。選擇兩個最長的克隆，HT2和HT9進行分析。HT2含有4.7Kb的插入(對應于SEQ ID NO30的核苷酸2974并伸展到比SEQ ID NO1較遠的下游)，HT9含有5485bp的插入(對應于SEQ ID NO30的核苷酸2152到7624)。核苷酸序列分析揭示在兩個cDNA克隆的共同區域有一個在HT9位于核苷酸3233的T單一堿基對插入。該核苷酸插入造成預期的氨基酸讀框遷移然后中止，認為是由逆轉錄酶在克隆HT9造成的錯誤。
為了分離含有附加2.5Kb的克隆，從三個附加cDNA文庫中各篩選了一百萬個克隆人胎腦cDNA文庫(Stra標記ene#93206)，人心臟cDNA文庫(Stra標記ene#93207)，以及人主動脈cDNA文庫(ClontechLaboratories#HL1136a，Palo Alto，California)。HT9的大多數5’區的序列被用于設計和合成兩個寡核苷酸，oHT9-1 5’-CCTAGTCCAGTAAAACTTGC-3’(SEQ ID NO15)和oTH9-4 5’-TTTGCGGCCCTTCCAATATC-3’(SEQ ID NO16)，它們被用于在產生上述探針的條件下產生一個317bp PCR探針。雖然從心臟或主動脈cDNA文庫中沒有分離到陽性克隆，但從胎腦文庫中得到了兩個陽性克隆。這些克隆之一，HFB2，包括一個cDNA4.5Kb插入片斷，該片斷包括大約2300bp的附加序列。HFB2插入片斷對應于SEQ ID NO30的核苷酸1到3194。
從克隆HFB2，HT9和HT2構建了編碼MCCS1α的復合cDNA。通過用限制酶KpnI和SalI消化HFB2產生一個含有復合克隆5’端的片斷，用KpnI和NotI消化HT9產生一個包括復合克隆3’端的片斷，然后將分離的片斷連接到已用SalI和NotI消化的pBS SK-(Stra標記ene)載體上，使這三個克隆連接在一起。含有一個核苷酸插入的HT9片斷區域被用含有克隆HT2的核苷酸3174到5282的EcoRV片斷取代。最終的含有一個7621bp插入片斷的質粒被命名為pBSHFB2HT2-27(ATCC69951)。DNA及推斷的插入片斷的氨基酸序列分別示于SEQ ID NOs1和2。cDNA的編碼區域以在333核苷酸的ATG開始，以在7560核苷酸的終止密碼子結束，預示一個2409氨基酸的編碼序列和265kD的蛋白。cDNA插入片斷的蛋白產物被命名為MCCS1α。在質粒pBSHFB2HT2-27(ATCC 69951)中插入片斷的隨后的序列分析揭示了在SEQ ID NO1的排序錯誤。改正的插入片斷DNA和推斷的氨基酸序列分別列于SEQ ID NOs23和24。質粒pBSHFB2HT2-27中插入片斷的更進一步的序列分析揭示了在SEQ ID NO23的排序錯誤。在核苷酸位置6317(SEQ ID NO23)，錯誤地包括了一個“G”并且在位置6338和6339之間序列丟失了一個“A”。MCCS1α的改正序列在SEQ IDNOs30和31提供。
比較MCCS1α的預期氨基酸序列和從克隆517預期的MCCS1β的部分氨基酸序列揭示在MCCS1α產物中存在七十個氨基酸缺失。MCCS1β克隆517氨基酸序列對應于SEQ ID NO31的MCCS1α氨基酸1611到2410。在MCCS1α中七十個氨基酸的缺失(即此處應插入七十個氨基酸以產生等同于MCCS1β的產物)發生在SEQ ID NO31的氨基酸2065和2066之間，激酶結構域上游的十七個氨基酸。因為兩種克隆都保持了可讀框，cDNA克隆pBSHFB2HT2-27明顯地產生自兩者之一的已剪切mRNA。含有激酶結構域的羧基端區域在MCCS1α(SEQ IDNO31的氨基酸2083到2410)和MCCS1β克隆(SEQ ID NO4的氨基酸543到870)是等同的。
含有MCCS1β(具有七十個氨基酸插入片斷)完全編碼序列的復合克隆示于SEQ ID NO32。從該克隆推斷的氨基酸序列示于SEQ IDNO33。此克隆是通過用HT2中所含有的HT2 3’端BstXI和NotI位點間的序列替換剪切第3229個核苷酸后面的BSTXI位點和pBSHFB2HT2-27(SEQ ID NO1)3’端多聚接頭序列中NotI位點之間的序列而構建的。所以該克隆含有連接到與SEQ ID NO3(編碼SEQ ID NO4的氨基酸1到870)克隆517的1到2610核苷酸相同序列的等同于SEQ ID NO1(編碼SEQ ID NO2的氨基酸1到1609)的MCCS1α核苷酸1到5159的序列。如上指明的，隨后的序列分析揭示在SEQ ID NO1的核苷酸1到5159中有錯。改正的MCCS1βDNA和推斷的包含出現于MCCS1αSEQID NOs23和24的相同改正的氨基酸序列列在SEQ ID NOs25和26。SEQ ID NO25克隆表示一個編碼全長MCCS1β激酶的cDNA。SEQ IDNOs32和33給出包括糾正MCCS1α克隆重測序識別的錯誤的MCCS1β的其它序列。
MCCS1產物可以基于同其它PIK相關激酶的相似性被分成三個區域氨基端區域(SEQ ID NO31的MCCS1α氨基酸1到1081和SEQ IDNO33的MCCS1β氨基酸1到1150)，與rad3+相似的區域(SEQ IDNO31的MCCS1α氨基酸1082到2082和SEQ ID NO33的MCCS1β氨基酸1151到2151)以及包括激酶結構域的PIK區域(SEQ ID NO31的MCCS1α氨基酸2083到2410和SEQ ID NO33的MCCS1β氨基酸2152到2480)。氨基端區域和rad3+區域是調控區域，它調節酶的激酶活性并參與與相關蛋白的相互作用。
MCCS1α和MCCS1β的核苷酸及氨基酸序列與其它PIK相關及非PIK相關激酶序列的比較結果見表1。特別地，MCCS1α的3’末端(編碼激酶區域的SEQ ID NO30的核苷酸6579到7562)，MCCS1β的3’末端(編碼激酶區域的SEQ ID NO32的核苷酸1627到2379)，MCCS1α的rad3+區域(SEQ ID NO30的核苷酸3576到6578)，MCCS1β的rad3+區域(SEQ ID NO3的克隆517核苷酸1到1626)，與人TAM[Savitsky等，見上]，人DNA-PK[Huntley等，Cell，82849-856(1995)]，人FRAP[Brown等，見上]，人p110[Hud等，Mol.Cell.Biol.，13(12)7677-7688(1993)]，釀酒酵母MEC1[Weinert等，Genes Dev.，8(6)652-665(1994)]，S.pombe rad3+[Seatond等見上和Hari等，Cell，82815-821(1995)]和cAMP依賴的蛋白激酶(PKA)[Beebe等，Mol.Endocrinol，4(3)465-475(1990)]的類似區域做了比較。在表1中對每一種激酶的核苷酸的相同性百分比見頂行，氨基酸的相同性百分比見中間行，氨基酸的相似百分比(即包括相同的氨基酸和氨基酸的保守變異)見底行。在此使用的保守變異表示生物學相似殘基。保守變異的實施例包括用疏水殘基如異亮氨酸，纈氨酸，亮氨酸或蛋氨酸取代另一個，或用單極殘基取代另一個，如用精氨酸取代賴氨酸，用谷氨酸取代天冬氨酸或用谷氨酰胺取代天冬酰胺等。在表中“ND”表示由于編碼此激酶(既rad3+)的核苷酸序列不能公開得到或激酶(既FRAP，p110β或PKA)缺少被比較的特殊結構域，因此沒有測定該值。
表1蛋白激酶 MCCS1α/MCCS1βMCCS1α MCCS1β激酶 rad3+ rad3+區域 區域 區域S.pombe rad3+ NDND ND5622 307246 53釀酒酵母 5142 44MECl 4521 246346 49人ATM 5041 413822 246046 47人DNA-PK 4339 432919 205345 49人FRAP 45ND ND37ND ND61ND ND人p110β45ND ND24ND ND54ND ND人PKA 39ND ND16ND ND39ND ND
實施例2通過基于PCR的試驗MCCS1基因定位于染色體3。含有各種從NIGMS人基因突變體細胞貯藏所[Drwinga等，Genomics，16311-314(1993)]得到的人染色體板人/嚙齒動物體細胞雜交體被用作模板。
基于MCCSlαcDNA序列的兩個寡核苷酸引物oDH23(SEQ IDNO12)和oDH26 5’TGGTTTCTGAGAACATTCCCTGA3’(SEQ IDNO19)被用來擴增該基因的一部分。引物產生237bp PCR產物。PCR條件由25μl反應體積中50ng基因組DNA，每個引物0.5μg，200μMdNTPs，1.5mM MgCl2，1×PCR緩沖液(Perkin Elmer-Cetus)，以及1單位的AMpli標記聚合酶(Perkin Elmer-Cetus)組成。在480型Cetus Thermocycler上，樣品變性4分鐘，然后按變性，退火，分別45秒，30秒和45秒的延伸時間共循環35次。生成的5μl PCR產物在3％瓊脂糖凝膠上電泳并用溴化乙錠染色。對應于人/嚙齒動物染色體3的雜交體的DNA生成陽性擴增產物。
在第二套擴增反應中，相同的寡核苷酸引物用于把MCCS1基因亞定位到染色體3上特定區域。用于這些擴增的模板由從帶有染色體3截短的病人得到的DNA樣品組成[Leach等，Genomics，24549-556(1994)]。擴增如前面段落描述的那樣進行。陽性擴增產物的形式將定位收縮于q21和q25.1之間。
實施例3編碼PIK相關激酶MCCS1β羧基端部分的多核苷酸通過在大腸桿菌中重組技術表達。
構建兩個大腸桿菌表達載體，表達針尖融合蛋白標記物表達/純化系統(Promega，Madison，Wisconsin)中激酶的COOH末端423或571氨基酸殘基。簡要地說，編碼激酶(SEQ ID NO3的核苷酸1339到2630或核苷酸898到2630)的羧基端部分的DNA序列在框架中被融合到一個來自propionibacterium shermanii轉羧酶復合物的13kD肽的羧基末端。該區域在大腸桿菌中經過生物素化，從而提供了一個監測表達和融合蛋白純化的方法。表達啟動自針尖Xa3的tac啟動子。融合蛋白表達用0.1M IPTG誘導并用鏈霉親和素堿性磷酸酶如生產商描述的以假-Western格式證明。
實施例4用桿狀病毒表達系統，MCCS1的重組體變型在酵母或在SF9昆蟲細胞也可以表達。FRAP激酶已被表達，純化并且在桿狀病毒表達系統[Brown等，見上]表達后有酶促活性。
MCCS1的編碼區在氨基端被融合到異源肽序列，如FLAG標記MDYKDDDDK(SEQ ID NO20)或一個六-組氨酸標記，并重新構建到適當的載體。一旦在昆蟲細胞表達，識別FLAG標記(Eastman Kodak，Rochester，New york)的單克隆抗體用于純化大量的FLAG-PIK相關激酶融合蛋白。感染的昆蟲細胞溫育48小時并在裂解緩沖液(25mM 2-甘油磷酸，50mM磷酸鈉pH7.2，0.5％Triton-X100，2mMEGTA，25mM氟化鈉，100μM釩酸鹽，1mM PMSF，1μl/ml亮抑酶肽，1μl/ml胃酶抑制劑，1mM苯甲脒，和2mM DTT)中裂解。表達的FLAG融合蛋白通過含有抗FLAG抗體M2親和樹脂(Eastman Kodak)的柱子純化。該柱用20倍柱體積的裂解緩沖液沖洗，然后5倍柱體積的0.5M氯化鋰，50mM Tris pH7.6，1mM DTT洗，然后用0.1M甘氨酸pH3.0隨后立即中和或通過用FLAG肽競爭洗脫來洗脫。對六-組氨酸標記的蛋白，Ni-NTA瓊脂糖(Qiagen)被用于蛋白純化。
專利申請U.S.S.N.08/558,666申請后不久，Antony M.Carr和合作者(個人通訊)描述了鑒定為ATR的基因。基于ATR和MCCS1之間氨基酸序列的比較，ATR看來好象編碼與MCCS1相同或密切相關蛋白。DNA和ATR的推斷氨基酸序列分別示于SEQ ID NOs28和29。ATR和MCCS1β之間的序列差異如下。ATR在N-末端包括附加的98個氨基酸殘基。在核苷酸位置1284(SEQ ID NO32)有一個保守堿基從MCCS1β的“A”變為ATR的“T”，并且在核苷酸位置4176有一個附加的保守堿基從MCCS1β的“C”變為ATR的“T”。
FLAG標記物融合在缺少開始66個ATR氨基酸的截短的ATR分子的氨基末端。FLAG標記物通過PCR如下加入。寡聚物FLAG-ATR(5′-CGGGATCCGCCATGGACTACAAGGACGATGACAAGATGTTGCTTGATTTC-3′)，和HFB24(5′CTTAAGCCGCATGAGCACACCGTC-3′)被用于下列PCR反應100ng pcDNAATR(從Antony M.Carr得到)做為模板；1×PCR緩沖液(Perkin-Elmer Cetus)；1.5mM MgCl2，dATP，dGTP，dCTP和TTP各200μM，每個引物10ng/μl；1UAmpli標記(Perkin-Elmer Cetus)。反應在94℃變性4分鐘，然后進行94℃30秒、60℃30秒和72℃30秒循環30次。得到的約800bp PCR產物用BamH1和Nhe1消化，連接到哺乳動物ATR表達質粒pcDNAAT用BamH1和BstXI消化得到的10kb片斷以及2.5kbBstXI到NheI片斷含有的編碼ATR序列的剩余部分。序列分析證實加上了FLAG標記。該質粒含有的插入片斷然后用于構建能表達FLAG標記的ATR截短物的桿狀病毒表達質粒。來自pDTMATR，BamH1到BstXl片斷含有的5’端ATR和BstXI到SalI片斷含有的3’ATR連接到已用BamHI和SalI消化的桿狀病毒表達載體pFB(Gibco.BRL)上。此質粒命名為pFMBCCSβFLAG。
ATR的全部編碼區氨基末端用PCR融合到六個組氨酸標記上。多核苷酸MCCS6his(5′-CGGGATCCAGCATGCATCACCATCACCATCACATGGGGGAACATGGGC-3.)和FrplR(″5′-CATGACCACTGGCCATTCCACACG-3′)用于PCR反應以向編碼ATR氨基端的序列加六個組氨酸標記。PCR條件如下100ng PstA 12ATR(從Antony M.Carr得到)做為模板；1×PCR緩沖液(Perkin-Elmer Cetus)；1.5mM MgCl2，dATP，dGTP，dCTP和TTP各200μM，每個引物10ng/μl；1U Ampli標記(Perkin-Elmer Cetus)。反應在94℃變性4分鐘，然后進行94℃30秒、60℃30秒和72℃30秒循環25次。約800bp PCR產物用BamH1和Msc1消化，連接到另外兩個片斷用BamH1和BstXI消化pcDNAATR得到的10kb片斷和含有ATR編碼序列的剩余部分的大約3kb MscI到BstXI片斷。序列分析證實加入了六個組氨酸標記得到的編碼以六個組氨酸標記的全長ATR分子的質粒被命名為pcDNA6hisATR。
為了構建表達ATR全部編碼序列的桿狀病毒表達質粒，pFMBCCSβFLAG的1.2kb BamHI到AgeI片斷連接到pcDAN6hisATR的BamI到AgeI片斷得到的稱作pFB/HisX6MCCS-1質粒轉化到大腸桿菌菌株DH5α(Gibco/BRL)用于篩選重組體。該質粒用Promega“Wizard”mini-prep試劑盒純化，然后用Gibco/BRL描述的Cellfectin方法轉化到大腸桿菌αSF9細胞(Invitrogen)中。
轉染后48小時收獲SF9細胞沉淀和轉染細胞產生的桿狀病毒。該病毒在4℃含有10％FBS，青鏈霉素和慶大霉素的Grace’s完全培養基中儲存。該病毒樣品用來制造高滴度(P2)病毒儲液。此P2病毒儲液用于感染50ml SF9細胞培養物。感染后48小時收集細胞并以低速離心，在不裂解的情況下沉淀細胞。裂解前細胞沉淀在-20℃儲存24小時。細胞在5ml裂解緩沖液(50mM Tris，pH8.0；500mM NaCl；1％NP40；100μMPMSF)中裂解。用抗AgDH2的多克隆抗體做探針通過免疫印記證實ATR的表達。FBHisX6 ATR桿狀病毒產生一種約300kDa蛋白，它與抗AgDH2抗體免疫反應并與小鼠睪丸細胞提取物中的蛋白共遷移。
P2病毒儲液還用于感染兩升SF9細胞培養物。感染后48小時收集細胞，低速離心，在不裂解的情況下沉淀細胞并儲存于-20℃。100ml此培養物的細胞沉淀在7.5ml裂解緩沖液(50mM磷酸鈉ph7.2；0.5％NP40；10mM咪唑，25mM氟化鈉，100μM Na3VO4；0.5mMAEBSF；1μg/ml亮抑酶肽；1μg/ml抑胃酶肽A)中裂解并在冰上保溫15分鐘。裂解物以10000×g離心30分鐘。去掉上清液，由于核破裂得到的裂解物中DNA通過20號針頭抽吸剪切。顆粒物質通過0.8微孔濾膜和0.2微孔濾膜過濾除去。澄清的裂解物調至含5mM β-巰基乙醇和0.4M NaCl。在澄清裂解物上樣前一個1ml Ni-NTA-瓊脂糖柱(Qiagen)用緩沖液A(0.4M NaCl；5mMβ-巰基乙醇；0.1％Triton X-100；50mM磷酸鈉，10mM咪唑；25mM氟化鈉，100μM Na3VO4；0.5mMAEBSF；1μg/ml亮抑酶肽；1μg/ml抑胃酶肽A)平衡。樣品以0.25ml/min的流速載樣，5ml緩沖液A洗，然后以10ml在緩沖液A中50到500mM咪唑的梯度洗脫。按0.5ml部分收集，并按下面方法試驗激酶活性。每部分的10c在激酶緩沖液，10μCi32PγATP，10μM ATP，以及5μg底物PHAS-1(Stra標記ena)并在37℃溫育20分鐘。反應液然后點到磷酸纖維素離心柱上，以2500×g離心，用0.5ml 75mM磷酸洗兩次并用0.5ml無水乙醇洗一次。磷酸纖維素盤然后轉移到閃爍管中，記錄每分鐘摻入到PHAS-1蛋白中的數目。發現4到9部分對PHAS-1有活性，免疫印跡分析證實ATR也存在于相同的部分中。
編碼質粒DNA的MCCS1轉化到一個esr1-1二倍體酵母菌株(Mataleu2-1 his4-4 can1 ura3 cyh2 ade6 ade2 esr1-1/MAT a leu2-27 his4 trp1met2 ade2 esr1-1)，細胞在含有半乳糖或葡萄糖的培養基中生長到對數中期。細胞沉淀等所有步驟在4℃進行。細胞糊重懸于緩沖液(20mMTris pH8.0，300mM NaCl，10％甘油，0.1mM PMSF，0.25mg/ml胃酶抑制劑，亮抑酶肽，和抑蛋白酶肽)中并在弗氏亞碎器中或用玻璃珠裂解。裂解用顯微鏡核實，隨后低速(10K)離心和高速(100K)離心，上清液上樣到預先用1×緩沖液洗過的1.5ml Ni-NTA瓊脂糖(Qiagen，Inc.，chatsworth，CA)柱上。柱子用6倍柱體積的緩沖液洗。該柱子分步用含10mM，50mM，100mM和250mM咪唑的緩沖液各8ml洗脫。分部收集并用每個洗脫峰的15μl進行Western分析。激酶活性如上描述測定。
實施例5對MCCS1特異的多克隆和單克隆抗體通過本領域標準技術產生。
兩種不同的細菌表達質粒，pGEX1-MEC和pGEX3-MEC，用于做為谷胱甘肽S轉移酶(GST)羧基端融合物的MCCS1多肽部分重組產物的構建。兩種質粒pGEX1-MEC和pGEX3-MEC分別用于在標準免疫接種方法中使用的抗原抗原AgDH-2和AgDH-3的產生。pGEX1-MEC含有編碼融合到pGEX1載體(Pharmacia Biotech，Milwaukee，Wisconsin)中GST的SEQ ID NO4的566到879氨基酸殘基的EcoRI片斷；pGEX3-MEC含有編碼融合到pGEX3載體(Pharmacia Biotech)中GST的SEQ ID NO4的118到576氨基酸殘基的EcoRI片斷。pGEXtac啟動子用0.1mM 1PTG誘導導致處于不溶形式(包含體)的每種融合蛋白的高水平表達。誘導的培養基用弗氏亞碎器裂解后，AgDH-2和AgDH-3提取物經含有0.1M NaCl，0.01M Tris pH7.5，和0.001MEDTA(STE)的35％葡萄糖溶液離心。然后沉淀液洗兩次并重懸于STE中。
為了在兔中產生單克隆抗血清，AgDH-2和AgDH-3進一步用制備SDS聚丙烯酰胺凝膠電泳純化，并從膠片上電洗脫出每個抗原。雌性新西蘭白兔的初級免疫接種是用與弗氏完全佐劑混合的每種抗原200μg注射到隨機的多個部位。隨后的免疫接種是用與弗氏非完全佐劑混合的100μg抗原在約21天間隔進行，測試血液在接種3，4和5次后抽取。人睪丸組織提取物的Western印記分析說明對免疫中大約270kD蛋白的抗體有活性，而非免疫前抗血清。另外，免疫血清顯示對實施例3描述的MCCS1針尖融合蛋白的活性，提供了MCCS1特異抗體產生的事實。
MCCS1特異抗體按如下方法純化。制備的AgDH-2和AgDH-3包含體偶合到溴化氰(CNBr)活化的瓊脂糖凝膠(Pharmacia，Alameda，CA)。2mg抗原溶解在1％SDS(終體積45ml)并在偶聯緩沖液(0.1MNaHCO3/0.1％SDS)中透析過夜。在用CNBr瓊脂糖溫育前加入0.5ml 5MNaCl到每一個制備抗原中。0.4gm凍干的CNBr瓊脂糖(每個抗原)重懸于1mM Hcl并在scintered玻璃漏斗中用250ml 1mM HCl洗，HCl在15分鐘內分幾部分加入。然后HCl洗過的CNBr瓊脂糖轉移到一個15ml撳帽管中并用5ml偶聯緩沖液沖洗二次。透析過的抗原樣品加入到洗過的瓊脂糖中，然后在緩慢旋轉輪上室溫溫育1.5小時。瓊脂糖用5ml偶聯緩沖液洗一次，用10ml 0.1M Tris pH8.0洗一次，然后在10ml 0.1M TrispH8.0中室溫溫育2小時以封閉樹脂上的任何剩余活性基團。用SDS-PAGE分析判斷偶聯效率為60-80％。抗原柱然后用15ml 6M鹽酸胍(除去未偶聯抗原)，25ml緩沖液A(30mM Tris pH7.4)，15ml緩沖液B(4.5M MgCl2/1mg/ml BSA/50mM Tris pH7.4)，然后用50ml緩沖液A洗。30ml來自已免疫動物(用AgDH-3免疫的兔4747和用AgDH-2免疫的兔4779)的兔血清經3小時流過此適當的抗原柱。柱子然后用20ml緩沖液A，40ml 1M鹽酸胍洗，再用另外20ml緩沖液A平衡。然后用10ml緩沖液B從抗原柱上洗脫下抗-AgDH-3和抗-AgDH-2抗體。按1ml部分收集，含IgG的部分合并，在1L磷酸鹽緩中液(PBS)中透析3小時，然后在1L含35％甘油的PBS中透析過夜。
通過用EDC按生產商(Pierce)所描述的把15-氨基酸肽(殘基1359-1373)偶聯到匙孔血藍蛋白上，然后把偶聯的免疫原注射到兔中來產生抗人ATM蛋白的抗肽抗體。隨后用等量體積的飽和氯化銨重懸并在PBS中透析，抗體首先從血清(#6076)中沉淀出來。使用按生產商描述的通過抗體肽偶聯到CNBr活化的瓊脂糖(Pharmacia)制備的肽柱實現親和純化。抗體然后結合到肽柱上并用2命令KCl-PBS洗。用20ml Sm NaI(在1mM硫代硫酸鈉中)實現洗脫，洗脫液立即在PBS中透析。
為了生成單克隆抗體，雌性Balb/c小鼠用50μg AgDH-2或AgDH-3免疫。另外的小鼠用已經與等摩爾比的mAb 61F3B結合的25到50μgAgDH-2或AgDH-3免疫，mAb 61F3B是對GST有特異活性的單克隆抗體。第三組小鼠用含AgDH-2或AgDH-3的聚丙烯酰胺凝膠片免疫。每組小鼠的免疫原在弗氏完全佐劑中制備，然后間隔約21天進行攻擊(弗氏非完全佐劑中25μg抗原)。產生單克隆抗體細胞株按如下方法分離。簡要地通過在補充以2mM L-谷氨酰胺，1mM丙酮酸鈉，100單位/ml青霉素，以及100μg/ml鏈霉素(RPMI)(Gibco，Cahada)的無血清RPMI1640中研磨免疫小鼠脾，形成單細胞懸液。該細胞懸液通過無菌70目Nitex細胞濾器(Bocton Dickinson，Parsippang，new Jersey)過濾，在200g離心5分鐘，洗兩次，在20ml無血清RPMI中重新懸浮沉淀。從三個新生Balb/c小鼠取出的胸腺細胞以此方法制備。
在融合前三天用含11％胎牛血清(FBS)(Hyclone Laboratories，Inc.，Logan，Utah)的RPMI保持在對數期的NS-1骨髓瘤細胞，在200g離心5分鐘，象前面描述的洗沉淀二次。洗后，每種細胞懸液在無血清RPMI中制成終體積10ml，取10μl按10∶100稀釋。取每種稀釋液20μl，與20μl含0.4％臺盼藍染色劑的0.85％鹽水(Gibco)混合，在血細胞計數計上計數。
2×108脾細胞與4×107NS-1細胞結合，離心，吸出上清液。輕拍試管取出細胞沉淀，并在1分鐘過程內攪拌加入2ml 37℃PEG 1500(在75mM Hepes，pH8.0中50％)(Boehringer Mannheim)，隨后在7分鐘內加入14ml無血清RPMI。另外加入16mlRPMI，細胞在200g離心10分鐘。傾去上清液后沉淀重懸于含15％FBS，100μM次黃嘌呤鈉，0.4μM氨基蝶呤，16μM胸苷(HAT)(Gibco)，25單位/ml IL-6(Mallinckrodt，Folerost，Pennsylvania)，和1.5×106胸腺細胞/ml的200ml RPMI中。板中的細胞在融合和篩選之間用18G針頭從每孔吸出約一半培養基并補充上述含10單位/ml IL-6和無胸腺細胞的接種培養基，進行3到4次。
當細胞生長達到60-80％融合度時(7-9天)，通過用AgDH2對AgDH3的ELISA篩選融合物。Immunlon4板(Dynatech，Cambridge，MA)用含100ng/孔蛋白的30mM碳酸鹽緩沖液，pH9.6于4℃覆蓋過夜。板用含100μg/孔0.5％魚皮明膠的PBS在37℃封閉1小時，用PBS洗三次，加入0.05％Tween 20(PBST)和50μl培養基上清液。37℃溫育30分鐘后，如上所述洗滌，加入在PBST中1∶10,000稀釋的偶聯山羊抗-小鼠IgG(fc)(Jackson ImmunoResearch，West Grove，PA)的辣根過氧化物酶50μl。板如上所述溫育，用PBST洗四次，加入由100μg/ml四甲基聯苯胺和含0.15μl/ml H2O2的100mM乙酸鈉，pH5.5組成的底物。在5-10分鐘加入50μl 15％H2SO4中止顏色反應。在板讀數器上讀取A490值。
在ELISA中呈陽性的雜交瘤的53個庫篩選與來自小鼠睪丸細胞裂解物的MCCS免疫印跡和免疫沉淀的能力。用小鼠睪丸提取物的免疫印跡分析在實施例6中描述。免疫沉淀完成如下。走6％聚丙烯酰胺凝膠并在192mM甘氨酸，25mM Tris堿，0.1％SDS，20％甲醇中轉移到Immobilon-PVDF膜上，然后在5％脫脂奶粉，20mM Tris pH7.5，100mMNaCl，0.1％Tween 20中封閉1小時，并切成適當數目的細條。初級抗體(孔上清液)在上面的封閉液中稀釋并室溫溫育1小時，在無奶封閉液中洗四次，在山羊抗小鼠IgG(H+L)HRP(BioRad #170-6516)中溫育，再在無奶封閉液洗，轉移到NEN Renaissance ECL試劑并顯影5分鐘。
免疫沉淀如下進行。50μl雜交瘤上清液于按實施例6所述制備的300μg睪丸細胞裂解物在冰上溫育1小時。加入30μl與兔抗-小鼠橋聯抗體(5μg/反應)(Pierce)預先結合的蛋白A瓊脂糖的50％勻漿，在4℃搖動溫育。免疫復合物在裂解緩沖液中洗三次，抗原/抗體復合物通過在SDS樣品緩沖液(2％SDS，20mM Tris pH6.8，20％甘油，0.001％溴酚藍)中煮沸洗脫。生成的上清液在6％SDS聚丙烯酰胺凝膠上分離，轉移到Immobilon-PVDE(Millipore)膜上并用親和純化的兔抗-AgDH2多克隆抗血清進行免疫印跡。克隆了四個雜交瘤并如實施例6所述在免疫印跡、免疫沉淀和免疫沉淀/激酶試驗中顯示其特性。這四個雜交瘤細胞株被指定為224B、224C(ATCC HB 12233)，244F(ATCCHB 12234)和224G。所有四個單克隆抗體經免疫印跡和免疫沉淀識別MCCS1。
實施例6MCCS1相關蛋白激酶活性用實施例5所述的MCCS1特異多克隆抗體免疫沉淀。
提取物從由Balb/c小鼠分離的新鮮睪丸組織制備。剪碎的睪丸在裂解液(50mM NaPO4，pH7.2；0.5％TritonX-100；2mM EDTA；2mM EGTA；25mM NaF；25mM 2-甘油磷酸鹽；1mM苯甲基氟磺酸[PMSF]；1μg/ml亮抑酶肽；1μg/ml胃酶抑制劑A；2mM DTT)中于冰上用緊密配合的dounce勻漿器勻漿10-15下，再在冰上保溫30分鐘。在TL-100臺式超速離心機(Beckman)，裂解物在13,000×g rpm上于4℃離心10分鐘以除去未破碎的細胞和其它不溶物。等分的細胞裂解物在液N2中快速冷凍并在-70℃保存。500μg睪丸提取物與5μg親和純化的抗-AgDH-2多克隆抗體或5μg純化的兔IgG(Zymed，So.San Francisco，CA)在1ml裂解緩沖液中在冰上于衡量離心管內溫育1小時。30μl蛋白A瓊脂糖玻璃柱(Repligen，Cambridge，MA)(已在裂解緩沖液中洗過)加入到提取物中，然后在搖動平臺上于4℃溫育另外的30分鐘。免疫復合物/蛋白A瓊脂糖玻璃柱用1ml裂解緩沖液洗四次，用1ml激酶緩沖液(25mMHepes pH7.7；50mM NaCl；10mM MgCl2；0.1％NP-40；2％甘油；1mMDTT)洗一次，然后含有10μCi ATP[50 Ci/mmol]的20μl激酶緩沖液中溫育20分鐘。在用6％聚丙烯酰胺凝膠分離前用20μl 2×SDS樣品緩沖液并加熱到100℃停止激酶反應。凝膠在20％甲醇/7％乙酸中固定化，放射自顯影前在Whatman 3MM紙上干燥。盡管在控制免疫沉淀中很少或沒有明顯的磷酸化作用，但使用抗-AgDH-2抗體的免疫沉淀在約300kD和約18kD處含有兩條主要的磷酸化條帶。另外，有幾個小的磷酸化產物，包括一個與MCCS1蛋白本身共遷移的產物，如由Western印跡分析所證實的(見實施例8對Western印跡的描述)。約300kD蛋白的磷氨基分析證實磷酸絲氨酸殘基的存在。5μg AgDH-2(而非AgDH-3)的加入顯著地減少或消除在免疫沉淀中發現的MCCS1相關激酶活性。
實施例7MCCS1在各種人組織中的表達形式由Northern印跡雜交檢查。
含有來自各種人組織源的大小分級的含polyA+RNA 2μg的尼龍膜從Clontech Laboratories，Inc.得到，嚴格遵守生產商提供的雜交方法，只是為了減少與相關序列的交叉雜交的可能性，最終的洗脫是在55℃進行，而非50℃。使用PCR產生的32P標記DNA雜交探針。編碼MCCS1α的COOH末端30％的DNA被用作模板在32P-dCTP存在下來擴增1.3kb片斷，使用的引物是279-3 5’TGGATGATGACAGCTGTGTC3’(SEQ IDNO21)和279-6 5’TGTAGTCGCTGCTCAATGTC3’(SEQ ID NO22)。
Northern印跡的結果顯示MCCS1在廣泛的人組織中做為一個約9kbmRNA被表達。睪丸組織含有高水平的MCCS1 mRNA，盡管轉錄在小腸，卵巢，前列腺，胸腺，脾，心臟，外周血淋巴細胞，結腸，腦，胎盤，骨骼肌肉，腎和胰中也被表達。
MCCS1 mRNA在人腫瘤細胞株的表達也是用從Clonetech得到的人腫瘤細胞株RNA印跡檢測。RNA印跡含有來自細胞株HL-60(早幼粒白血病)，Hela(子宮癌)，K-562(慢性成髓白血病)，MOLT-4(成淋巴細胞白血病)，Raji(布氏淋巴瘤)，SW480(結腸腺癌)，A549(肺癌)和G361(黑色素瘤)的RNA。Northern印跡分析按生產商指導的完成，雜交用MCCS1部分克隆HFB2的2.0kb Kpnl-Sall片斷在65℃完成。在HL-60，Hela，K-562，Raji，Sw480和G361細胞株觀察到表達，在G361細胞株發生最高水平的表達。在MOLT-4和A549細胞株中觀察到可測得但低水平的表達。
實施例8正常和輻射的小鼠睪丸和小鼠胚胎中MCCS1 mRNA和蛋白的表達通過原位雜交、免疫染色和/或免疫印跡檢查。原位雜交從雄性Balb/c小鼠收獲正常和輻照小鼠睪丸。組織切成6μm厚度的切片，放到Superfrost Plus(VWR Scientific)載玻片上，室溫空氣干燥過夜。如不立即使用，切片在-70℃保存。組織切片在含4％低聚甲醛的PBS中于4℃固定化20分鐘，在4℃每一級(70％，95％，100％乙醇)脫水1分鐘，然后室溫空氣干燥30分鐘。載玻片在0.25％(v/v)乙酸酐(Sigma)/0.1M三乙醇胺pH8.0溶液中攪動下室溫酰化10分鐘，攪動下在0.2×SSC中室溫沖洗10分鐘，并如上所述脫水和空氣干燥。組織與來自小鼠MCC S1 DNA并用地高辛標記的單鏈mRNA進行原位雜交，該mRNA通過體外RNA轉錄摻入地高辛-UTP(Boehringermannheim)。標記的核糖探針(見SEQ ID NO27中的序列)(1μg/切片)和焦磷酸二乙酯(depc)處理的水加入到雜交緩沖液，終濃度是50％甲醇胺，0.3M NaCl，20mM Tris pH7.5，10％葡聚糖磷酸酯，1×Denhard溶液，100mM二硫蘇糖醇(DTT)和5mM EDTA，無RNase 22×22蓋玻片覆蓋。在切片和探針溶液中的mRNA通過在爐中加熱載玻片到85℃10分鐘來變性。雜交在50℃過夜(12-16小時)完成。
雜交后，切片在4×SSC/10mM DTT中室溫洗1小時，然后在50％甲醇胺/2×SSC/10 mM DTT中50℃洗30分鐘，在500mM NaCl，10mM Tris-HCl，1mM EDTA，pH7.5(NTE緩沖液)的溶液中37℃洗30分鐘，在含10μg/ml RNase A(Boehringer Mannheim)的NTE緩沖液浴中37℃洗30分鐘，在NTE緩沖液中于37℃洗15分鐘，在2×SSC中室溫洗15分鐘，在0.1×SSC中室溫洗15分鐘，在100mM Tris-HCl，150mM NaCl，pH7.5(緩沖液1)中室溫洗2分鐘。為探測標記的核酸探針，切片在5％正常羊血清(Harlan Bioproducts for Science，Indianapolis，IN)和含0.3％Triton X-100(Sigma)的緩沖液1的溶液中于室溫，溫和攪動下封閉30分鐘，隨后150μl/切片羊α地高辛-金偶聯物(GoldmarkBiologicals，Philipburg，Pa)用于該組織并在室溫溫育2小時。載玻片然后在緩沖液1中5分鐘洗三次，在無菌去離子水中3分鐘洗5次，過量液體從載玻片上吸干，銀增強和始發溶液(Goldmark Biologicals)各2滴加入到每個玻片上。讓該化學反應室溫進行23分鐘，然后切片在無菌去離子水中徹底沖洗，在Nuclear Fast Red(載體)中對染，再在無菌去離子水中沖洗，室溫空氣干燥過夜并用Cytoseal 60(VWR)制成標本。
在正常和照射的小鼠二者的睪丸觀察到精原細胞和精母細胞的細胞質中的信號。照射的睪丸中表達水平未升高超過正常睪丸。免疫染色來自正常的雄性Balb/c小鼠的睪丸組織以6μm厚度切片，放到Superfrost Plus(VWR Scientific)載玻片上，室溫空氣干燥過夜。如不立即使用，切片在-70℃保存。切片在室溫于冷(4℃)丙酮中固定化10分鐘；一旦載玻片從丙酮中取出，讓溶劑從切片上揮發。每一個組織切片用150μl在1×TBS中含30％正常大鼠血清(Harlan Bioproducts)，5％正常山羊血清(Vector Laboratories)和1％牛血清白蛋白(Sigma)的溶液室溫封閉30分鐘。封閉后，從切片小心吸干溶液，來自相同兔的抗AgDH-3和AgDH-2單克隆抗體和免疫前血清在封閉溶液中按1∶50和1∶100稀釋，并取100μl到每一個組織切片，在37℃溫育30分鐘。從切片上小心地吸干抗體溶液，未結合的抗體通過在1×TBS洗載玻片三次，每次5分鐘，從切片除去。過量的TBS從載玻片上吸去，100μl存在于Elite Rabbit IgG VectastainABC試劑盒(Vector)中，根據產品插入片斷制備的生物素化的山羊抗兔抗體加入到每一個切片并在37℃溫育15分鐘。溫育后，載玻片在1×PBS中洗兩次，每次5分鐘。隨后，100μl在含有5％正常大鼠血清和1％BSA的溶液中1∶100稀釋的鏈親和素-金偶聯物(Goldmark Biologicals)加入到每一個切片中，室溫溫育1小時。載玻片然后在1×TBS中洗3次，每次5分鐘，100μl含1％戊二醛的TBS緩沖液室溫加入到載玻片上5分鐘。然后載玻片在TBA中洗3次，每次5分鐘，再在無菌去離子水中洗4次每次3分鐘。過量的液體從每個載玻片上吸干，銀增強和始發溶液(Goldmark biologicals)各兩滴加到每個切片上。讓該化學反應室溫進行13分鐘，然后切片在無菌去離子水中徹底淋洗，在Nuclear Fast Red(Vector)中對染，再在無菌去離子水中沖洗，室溫空氣干燥過夜并用Cytosea160(VWR)制成標本。
在帶有兩個多克隆抗體的精原細胞和初級精母細胞檢測到了信號，從相同動物的免疫前血清未檢測到信號。免疫印跡新獲得的小鼠睪丸用剃刀片在冷PBS中切碎，用松散結合的dounce勻漿器產生細胞懸液。然后該細胞懸液用等體積的2×SDS樣品緩沖液煮沸。每個提取物的50μg等份在6％聚丙烯酰胺凝膠上分離，轉移到Immobilon膜(Millipore，Bedford，MA)上并用實施例5中親和純化的抗體，以及HRP綴合的山羊抗兔二代抗體和Renaissance增強的化學發光試劑盒分析抗MCCS1反應性。從新鮮小鼠睪丸制備的提取物含有一種由親和純化的抗血清識別的高分子量種類(約294kD)。兩種免疫前血清都未見到對此蛋白的活性。重要地，從每一個親和純化血清獲得的信號在抗體與對應免疫原的預溫育后是被特異封閉的。
總的來說，在精原細胞和處于減數分裂早期階段的初級精母細胞中的小鼠睪丸檢測到高水平的MCCS1 mRNA和蛋白。這暗示MCCS1在減數分裂細胞分裂中起重要的作用。減數分裂是細胞分裂的特殊形式，它在較高等真核生物中產生生殖細胞。有兩個減數分裂的主要特征使其與有絲分裂區別開來。減數分裂細胞分裂導致含有一套染色體的細胞，而有絲分裂細胞分裂導致遺傳學上相同的含有兩套染色體的細胞。減數分裂早期，在“減數分裂”過程中，姐妹染色單體在一些區域配對和經歷相互重組。在這一過程中，這些細胞易受DNA鏈斷裂的影響。在減數分裂過程中，細胞對DNA鏈斷裂的反應可能與非生殖細胞對IR誘導的DNA損傷的反應相似。這種解釋進一步被研究證實，這些研究證明MEC1在芽胞形成過程中上調10到20倍，表明MCCS1除了在DNA修復中的作用外，在減數分裂過程中也起重要的作用。
實施例9為了識別在發育小鼠睪丸中表達MCCS1的細胞，進行了減數分裂細胞種群中MCCS1表達的Westem印跡分析。如上面實施例8所描述的檢查了純化的粗線期精母細胞，圓精子細胞，濃縮精子細胞，印跡副睪精子細胞的提取物。
粗線期精母細胞，圓和濃縮精子細胞通過用膠原酶和胰蛋白酶-DNase1順序解離從成熟小鼠脫莢膜的睪丸制備。細胞通過在含2％-4％BSA梯度的滋養林格碳酸氫鹽培養基(EKPB)中以單位重力沉降速度分離成分離的種群。粗線期精母細胞和圓精子細胞種群每種至少80％純度，而濃縮精子細胞約40-50％純度(主要污染有去核的殘余體和一些圓精子細胞)。精子從尾副睪獲得。精原細胞的純化種群直接溶解于含40mM DTT的SDS樣品緩沖液中，加熱到100℃5分鐘，在每個樣品中蛋白的數量由酰胺黑方法測定。
在粗線期精母細胞發現了高水平的MCCS1蛋白，在圓精子細胞中該水平顯著下降。MCCS1蛋白水平在濃縮精子細胞種群中低得幾乎不能測定，這可能反映了制備過程中圓精子細胞的存在(見上面)。副睪精子中沒有檢測到MCCS1蛋白。所以Western分析確證了免疫細胞活性數據，并提出了MCC所在減數分裂細胞中的作用。
實施例10MCCS1的底物和與MCCS1相互作用的蛋白(例如，細胞循環關卡途徑的成員和使MCCS1集中于細胞中的蛋白)可以通過各種試驗鑒定。A.底物鑒定MCCS1的底物可以通過在試驗中摻入試驗化合物來鑒定對激酶活性。MCCS1激酶重懸于20μl激酶緩沖液(25mM Hepes pH7.4，25mMKcl，10mM MgCl2，1mM DTT，2％甘油，0.1％NP40，0.5mM ATP，10uCiγ32P-ATP)并在4μg試驗化合物(如，酪蛋白，組蛋白H1，或適當的底物肽)存在或不存在下溫育30分鐘。反應在12％PAGE凝膠上分離并放射自顯影前于Whatman紙上干燥。被激酶轉移到試驗化合物的磷酸摩爾數用放射自顯影或閃爍計數測量。磷酸的轉移表明試驗化合物是激酶的底物。
蛋白PHAS-1以被鑒定為體外ATP的底物(實施例4)。PHAS-1是一個熱和酸穩定的蛋白，它在體內響應胰島素和生長因子的幾個部位磷酸化。PHAS-1結合到mRNA戴帽結合因子，EIF-4E，并阻止戴帽的mRNAs的翻譯。PHAS-1在特定絲氨酸殘基的磷酸化導致PHAS-1從EIF-4E的分離，因而釋放戴帽mRNA翻譯的抑制作用。該機理允許蛋白響應特定刺激的快速合成。PHAS-1可以被幾種蛋白激酶包括對雷帕霉素敏感的蛋白激酶在體內磷酸化。由于雷帕霉素敏感的蛋白激酶，FRAP，與ATR有關，在FRAP和ATR之間底物特異性上可能有重疊和PHAS-1在體內是這兩種蛋白激酶的底物的假設是合理的。為了檢驗這一假設，從小鼠睪丸細胞提取物免疫沉淀的ATR或由桿狀病毒感染的SF9細胞(實施例4)純化的His-標記ATR，在含10μgPHAS-1的激酶緩沖液(25mM Hepes pH7.4，25mM KCl，10mM MgCl2，1mM DTT，0.1％NP40，10μM ATP和10uCiγ32P-ATP)中于37℃溫育20分鐘。因為已知磷酸化的PHAS-1結合于磷酸纖維素紙上，該反應點滴到磷酸纖維素離心柱上，在2500×g離心，用0.5ml 75mM磷酸洗兩次，用0.5ml無水乙醇洗一次。然后把磷酸纖維素圓盤這一到閃爍計數管中，記錄每分鐘摻入到PHAS-1蛋白的數目。ATR容易地磷酸化PHAS-1，而陰性對照顯示較少或無PHAS-1磷酸化。為了定位那個殘基被磷酸化，合成了下列含有絲氨酸和蘇氨酸殘基代表PHAS-1序列的肽。
肽PH-1MSGGSSCQTPSRAIPATRR(SEQ ID NO36)肽PH-2GDYSTTPGGTLFSTTPGGTRR(SEQ ID NO37)肽PH-3ECRNSPVTKTRR(SEQ ID NO38)肽PH-4GVTSPSSDEPRR(SEQ ID NO39)
肽PH-5MEASQSHLRR(SEQ ID NO40)肽PH-6RRNSPEDKRAGG(SEQ ID NO41)肽PH-7GEESQFEMDIRR(SEQ ID NO42)在相同激酶反應中檢測的這些肽以測定那個肽被ATR磷酸化。該肽然后在如實施例11所述的試驗中被用作ATR或MCCS1底物以鑒別調制劑。
相同的激酶反應也被用于測定已知是其它蛋白激酶底物的如組氨酸H1(Upstate biotechnology，Inc.，Waltham，NY)和髓鞘堿性蛋白(GibcoBRL，Gaithersburg，MD)那樣的蛋白是否是MCCS1和ATR的底物。在試驗條件下沒有觀察到組氨酸H1或髓鞘堿性蛋白的磷酸化。而且，來自p53已知是DNA-PK底物的肽在試驗中也沒有被磷酸化。。B.相互作用蛋白的鑒別相互作用蛋白可以通過下列試驗鑒別。
本發明考慮的首次試驗是雙雜交篩選。雙雜交系統是由酵母發展的[Chien等，proc.Natl.Acad.Sci.USA，889578-9582(1991)]，它基于活化報道基因的轉錄因子的體內功能重建。特別地，編碼與MCCS1相互作用蛋白的多肽如下分離在通過具有DNA結合區域和一個活化區域的轉錄因子調節的啟動子控制下，轉化或轉染用包含報道基因的DNA結構的適當宿主細胞；在宿主細胞表達第一雜交DNA序列，該序列編碼部分或全部MCCS1和DNA結合區域或轉錄因子的活化區域的首次融合；在宿主細胞中表達第二雜交DNA序列庫，該序列編碼部分或全部推定MCCS1結合蛋白以及DNA結合區域或不摻入首次融合轉錄因子的活化區域；在特定宿主細胞通過測定宿主細胞中報道基因產物的生成來測定MCCS1結合蛋白與MCCS1的結合；并從該特定宿主細胞分離編碼相互作用蛋白的第二雜交DNA序列。目前在試驗中優選使用的是驅動報道基因表達的lexA，lacZ報道基因，包含lexA DNA結合區域和GAL4反式激活區域的轉錄因子，以及酵母宿主細胞。
鑒別與MCCS1相互作用蛋白的其它試驗包括固定化MCCS1或一種試驗蛋白，可測定地標記非固定化結合部分，一同溫育結合部分并測定標記結合體的數量。結合標記物表明試驗蛋白與MCCS1的相互作用。
鑒別MCCS1相互作用蛋白試驗的其它類型包括在覆蓋(或浸漬)熒光劑的固體載體上固定化MCCS1或其片斷，用能夠激發熒光劑的化合物標記試驗蛋白質，使固定化的MCCS1與標記的試驗蛋白接觸，檢測熒光劑的光發射，并鑒定做為試驗蛋白的相互作用蛋白，它導致由熒光劑形成的光發射。另外，在試驗中可固定化推斷的相互作用蛋白并標記MCCS1。
實施例11MCCS1的調制劑包含MCCS1變體和其它的分子。調制劑會影響MCCS1激酶活性，其在細胞中的位置，和/或其與細胞循環關卡途徑成員的相互作用。目前優選的做為突變或開發選擇性調制劑的靶點的MCCS1區域包括下列四個部分MCCS1α氨基末端效應子區域(SEQID NO31的氨基酸1到1081)，MCCS1β氨基末端效應子的區域(SEQID NO33的氨基酸1到1150)，MCCS1αrad3+區域(SEQ ID NO31的氨基酸1082到2082)，MCCS1βrad3+區域(SEQ ID NO33的氨基酸1151到2151)，MCCS1αPIK區域(SEQ ID NO31的氨基酸2083到2410)，以及MCCS1βPIK區域(SEQ ID NO33的氨基酸2152到2480)。
具有在激酶區域突變的MCCS1變體做為放射敏感劑可能是有用的。由本發明特別預期的突變是在氨基酸2241位的MCCS1α天冬氨酸，在2246位的天冬酰胺，和在SEQ ID NO31的2260位的MCCS1α天冬氨酸用丙氨酸或蛋氨酸取代，以及在MCCS1β的相應突變。在rad3+基因的類似突變導致酵母對放射超敏。另外，發現在帶有AT的病人中ATM的激酶區域突變，AT是一種造成放射敏感性的疾病。
此外，組合庫，肽和肽模仿物，限定的化學實體，寡核苷酸，以及天然產物庫可以在如下所述的那些試驗中篩選做為調制劑的活性。
例如，用于鑒別MCCS1激酶活性調制劑的試驗涉及在含γ-32P-ATP和存在或不存在試驗化合物的外源激酶底物的激酶緩沖液中溫育MCCS1激酶樣品，并測定轉移到底物的磷酸摩爾數。例如，2μg 50mM咪唑洗脫液加入到激酶緩沖液中。(見實施例6)。反應在37℃溫育20分鐘，在放射自顯影或Western分析前SDS-PAGE分析樣品。與不存在試驗底物下磷酸轉移到底物的摩爾數相比存在試驗底物下磷酸轉移到底物的摩爾數增加說明該試驗化合物是所說的MCCS1激酶的活化劑。相反，與不存在試驗化合物下磷酸轉移到底物的摩爾數相比存在試驗化合物下磷酸轉移到底物的摩爾數減少說明該試驗化合物是所說的MCCS1激酶的抑制劑。
而且，鑒別調節MCCS1與其它蛋白的相互作用的化合物的試驗可包括在通過具有DNA結合區域和一個活化區域的轉錄因子調節的啟動子控制下轉化或轉染帶有含報道基因的DNA結構的適當宿主細胞；在宿主細胞表達第一雜交DNA序列，該序列表達部分或全部MCCS1和DNA結合區域或轉錄因子的活化區域的首次融合；在宿主細胞中表達第二雜交DNA序列，該序列編碼部分或全部與MCCS1相互作用蛋白和DNA結合區域或不摻入首次融合轉錄因子的活化區域；通過在特定宿主細胞由測定報道基因產物在試驗化合物存在和不存在下在宿主細胞的產生來檢測相互作用蛋白對MCCS1的結合，評價試驗化合物在MCCS1和相互作用蛋白相互作用的影響；鑒別調節化合物為那些與不存在調節化合物時報道基因產物的產生相比報道基因產物的改變產生的化合物。目前在試驗中優選使用的是推動報道基因表達的lexA啟動子，lacZ報道基因，包含lexA DNA結合蛋白區域和GAL4反式激活區域的轉錄因子，以及酵母宿主細胞。
鑒別調節MCCS1與一種相互作用蛋白相互作用的其它試驗包括固定化MCCS1或天然MCCS1相互作用蛋白，可測定地標記非固定化結合部分，一同溫育結合部分并測定試驗化合物在標記結合物數量上的影響，其中與試驗化合物不存在時標記化合物的數量相比試驗化合物存在時標記結合物的減少，說明試驗劑是MCCS1與蛋白相互作用的抑制劑。相反，與試驗化合物不存在時標記化合物的數量相比試驗化合物存在時標記結合物的增加，說明推定的調制劑是MCCS1與蛋白相互作用的活化劑。而由本發明考慮的鑒別調節MCCS1和一種相互作用蛋白之間結合的化合物的其它方法包括在涂有(或浸漬)熒光試劑的固體載體上固定化MCCS1或其片斷，用能夠激發熒光試劑的化合物標記相互作用蛋白，在試驗化合物存在或不存在下用標記相互作用蛋白接觸固定化的MCCS1，檢測熒光劑的光發射，并鑒別做為那些與不存在試驗化合物下熒光劑的光發射相比影響熒光劑光發射的試驗化合物的調節化合物。或者，在試驗中可以固定化MCCS1相互作用蛋白和標記MCCS1。
實施例12用于鑒別MCCS1或ATM調制劑的基于相比的互補實驗描述如下。
在一種類型的試驗中，宿主細胞(例如esr-1酵母細胞)用如實施例4所述的編碼MCCS1 DNA轉化。esr 1-1酵母菌株對用紫外(UV)光處理正常地敏感，但表達MCCS1或ATR的esr 1-1酵母細胞對用UV處理不再敏感。轉化的酵母細胞中加入試驗化合物，并測定試驗化合物對轉化的宿主細胞UV敏感性的影響。MCCS1或ATR活性抑制劑的試驗化合物恢復對轉化的esr 1-1細胞的UV敏感性。或者，esr 1-1tel1雙突變酵母細胞代替esr 1-1酵母細胞被用作宿主細胞。TEL1基因是與ATM同源的，TEL1突變在Morrow等，Cell，82831-840(1995)中有描述。本發明也特別地考慮到esr 1-1或esr 1-1tel1雙突變體酵母宿主細胞可以用編碼ATM的DNA(SEQ ID NO34)轉化。
在另外的實施方案中，試驗包括斷裂劑或代替用UV光處理(如，IR，羥基脲，或DNA損傷劑)的過程。用于該實施方案的適當的宿主細胞可以是那些對其它斷裂劑或過程敏感的。
互補試驗的其它類型包含哺乳動物宿主細胞，如來自AT病人細胞的細胞株。如上對酵母宿主細胞所述，哺乳動物細胞用編碼MCCS1ATR，或ATM的DNA轉化，然后加入試驗化合物。是MCCS1，ATR或ATM活性抑制劑的試驗化合物會恢復未轉化的宿主細胞的表型(如，對IR的敏感性)。
以上試驗能被用于鑒別抑制MCCS1，ATR和ATM活性的化合物或僅抑制其中一種酶活性的化合物。
在試驗的另外類型中，酵母或哺乳宿主細胞被用編碼包括MCCS1和ATM區域的各種組合的嵌合多肽轉化。MCCS1和ATM顯示結構的相反性，并且包含MCCS1和ATM的部分的嵌合多肽在解釋MCCS1和ATM兩者活性位點和結合區域中是有用的。編碼嵌合體的多肽可以通過對技術人員已知的標準分子生物學技術制備并在此做為示范。該嵌合多肽在宿主細胞中被表達，該嵌合體的調制劑可由此處公開的試驗鑒別。
實施例13MCCS1和ATM都包含在減數分裂I關卡中。由于這里證明了MCCS1有激酶活性，進行試驗以確定是否ATM擁有激酶活性。為了確定ATM的激酶活性，ATM被從MRC-5成纖維細胞(ATCC #171-CCL)中用多克隆抗血清6076免疫沉淀。MRC-5細胞是人肺胚胎二倍體成纖維細胞。MRC-5細胞從第19代ATCC獲得并保持在補充以10％胎牛血清，100單位/ml青霉素，100mg/ml鏈霉素，和100mM非必需氨基酸的極限必需培養基中。培養基和培養基補充物由Gibco LifeTechnologies獲得。細胞株保存在37℃含5％C的水飽和溫育箱內。
MRC-5細胞提取物通過在冰上用0.5ml裂解緩沖液I(50mMNaPO4，pH7.2；0.5％TritonX-100；2mM EDTA；2nM EGTA；25mMNaF；25mM 2-甘油磷酸；1mM苯甲基氟磺酸[PMSF]；1μg/ml亮抑酶肽；1μg/ml胃酶抑制劑A；2mM DTT)裂解10cm平皿的對數期細胞制備。用橡膠刮鏟從平皿上刮下細胞并在杯角超聲器(Sonifier250，BransonUltrasonics Corp.，Danburg，CT)中于100輸出功率超聲90秒，裂解液然后在一個4℃microfuge澄清2分鐘。通過加入10μg純化的兔IgG(Zymad)和30μl蛋白A瓊脂糖糊(Pierce)，隨后搖動下在4℃溫育60分鐘進行預清除。向預清除裂解物中加入10μg親和純化的6076抗血清(或10μg用0.04mg P45肽預封閉30分鐘的6076)，在冰上溫育60分鐘。通過加入30μl蛋白A瓊脂糖糊并搖動下在4℃溫育30分鐘，隨后在裂解緩沖液I中洗四次收集免疫沉淀。
通過用激酶緩沖液(25μM Hepes pH7.7；50mM NaCl；10mM MgCl2；0.1％NP-40；2％甘油；1mMDTT)洗一次，隨后在25μl含10μmATP+10μCiγ32P-ATP[50 Ci/mmol]的激酶緩沖液中37℃溫育20分鐘，進行激酶反應。在用6％聚丙烯酰胺凝膠分離前用加入20μl2×SDS樣品緩沖液并煮5分鐘停止反應。凝膠干燥并在-80℃加入到X-射線膠片(Kodak，XAR-5)上過夜。
對數期MRC-5細胞的10cm平皿用PBS洗一次，然后在含2％透析過的胎牛血清的Dulbeco改進的Eagle培養基(無甲硫氨酸)中溫育30分鐘。加入200μCi35S-甲硫氨酸(1000Ci/mmol TRAN35S-LABEL，1CNRadiochemicals)標記細胞2小時。標記的細胞然后用PBS洗一次并在免疫沉淀前于-80℃冷凍。
免疫沉淀復合物在激酶緩沖液中的溫育產生一個具有分子量約350,000與ATM在聚丙烯酰胺凝膠上共遷移的磷酸化產物。
用實施例5的抗-AgDH-2(MCCS1)多克隆抗血清免疫沉淀的ATR免疫復合物獲得了相似的結果。因而ATR和ATM看來能夠自身磷酸化或與蛋白激酶有關系。
為了測定ATR和ATM在減數分裂中的作用，在小鼠精母細胞的表面涂片上利用免疫染色技術來固定化ATR和ATM到睪丸染色體上。識別ATR和ATM的抗體利用抗Cor1小鼠抗體。Cor1是突觸染色體的一個軸向/傾向元素的成分[Dobson等，J.Cell Sci.，1072749-2760(1994)]當軸向元素開始在突觸出現前，在減數分裂細線期中的每個同系物的姐妹染色單體之間形成時出現Cor1染色體染色。做為同源二倍體突觸，在它們之間形成了來自兩個同系匹配的軸向元素和中心元素，完成稱為聯會復合體(SC)的結構。
當Cor1的短延伸開始在突觸的任何跡象前出現時，ATR和ATM都不能測定。當同系物開始突觸時，兩種蛋白在配對叉都可見到；然而，兩種蛋白的位置和行為顯著地不同。在正常的合線期細胞核，同系物突觸階段，ATR以小量短暫地在沿突觸的(未配對)軸不連續的集落出現。做為同系物突觸，ATR從這些位置消失。然而，在常染色體二價體的近側末端附近常見的突觸延伸區域，沿突觸軸存在ATR集落的聚集。在兩個軸元素的相似位置檢測到ATR。在全部常染色體不能發現其同源配對體的細胞核中，ATR集落沿這些突觸的軸的全長被檢測到。雄性，此處X染色體無同系物，ATR集落位于沿未配對的軸。
ATM也可顯現為集落，并在合線期階段首次做為同系物突觸被檢測到，但是ATM定位比ATR困難。當同源常染色體的軸向元素接觸時，沿突觸的軸首次發現ATM。然而，粗線期中期階段，常染色體突觸已完成后，ATM集落出現在X染色體軸上。ATM定位持續保留在完全突觸的二價體進入粗線期，一種在小鼠卵母細胞中持續3天，在小鼠酵母細胞中持續6天的亞階段。在粗線期期間，集落的數目逐漸下降，在最終消失在中到晚粗線期之前短暫地穩定在粗線期中期。所以，ATR和ATM蛋白姐妹在減數分裂I的特有階段起重要和互補的作用。
ATR的參與看來在減數分裂前期的早期是短暫的，而ATM的作用似乎更長。然而，ATR和ATM兩者通過完成相似的關卡功能協調減數分裂前期的各種事件。
前述的用作說明的實施例涉及目前發明的優選實施方案，期待本領域技術人員想到的其許多的修改和變動。所以僅有如出現在附加權利要求那樣的限制應放在本發明的范圍內。
序列列表(1)總說明(i)申請人ICOS公司(ii)發明題目細胞周期關卡與PIK相關的激酶材料和方法(iii)序列數目42(iv)通訊地址(A)收信人Marshall，O’Toole，Gerstein，Murray&borun(B)街道6300 Sears Tower，233 S.Wacker Dr.
(C)城市芝加哥(D)州依利諾(E)國家美國(F)郵政編碼60606(v)計算機可讀方式(A)介質類型磁盤(B)計算機IBM PC兼容機(C)操作系統PC-DOS/MS-DOS(D)軟件PatentIn Release#1.0，#1.30版(vi)當前申請數據(A)申請號(B)歸檔號(C)分類(viii)代理人資料(A)姓名Noland，Greta E.
(B)注冊號35,302(C)參考/摘要號27866/33607(ix)電信資料(A)電話(312)474-6300(B)電傳(312)474-0488(C)用戶電報25-3856(2)SEQ ID NO1的說明(i)序列特征(A)長度7621個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型cDNA(vii)直接來源(B)克隆pBSHFB2HT2-27(ix)特征(A)姓名/符號CDS(B)位置333..7559(xi)序列描述SEQ ID NO1CTTGTGAAGA GAATGTTTTA CACTCTIGTT AGTGAAGTTT ATTCTTTAAA AGTCAATCGT 60CAAGGATTTA GCAAATGAAT TAGCACTTCG GATATACTTG TTTATTTAAT ATCTTTTTTG 120TTTATTTCAA AGAATTCAGT AATTGGATCA TAACGAGACT TCTGCGGATT GCAGCAACTC 180CCTCCTGTCA TTTGTTACAC AAGAAAATCT GTGAAGTCAT CTGTTCATTA TTATTTCTTT 240TTAAAAGCAA GAGTCCTGCT ATTTTTGGGG TACTCACAAA AGAATTATTA CAACTTTTTG 300AAGACTTGGT TTACCTCCAT AGAAGAAATG TG ATG GGT CAT GCT GTG GAA TGG 353Met Gly His Ala Val Glu Trp1 5CCA GTG GTC ATG AGC CGA TTT TTA AGT CAA TTA GAT GAA CAC ATG GGA 401Pro Val Val Met Ser Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly10 15 20TAT TTA CAA TCA GCT CCT TTG CAG TTG ATG AGT ATG CAA AAA TTA GAA 449Tyr Leu Gln Ser Ala Pro Leu Gln Leu Met Ser Met Gln Lys Leu Glu25 30 35TTT ATT GAA GTC ACT TTA TTA ACG GTT CTT ACT CGT ATT ATT GCA ATT 497Phe Ile Glu Val Thr Leu Leu Thr Val Leu Thr Arg Ile Ile Ala Ile40 45 50 55GTG TTT TTT AGA AGG CAA GAA CTC TTA CTT TGG CAG ATA GGT TGT GTT 545Val Phe Phe Arg Arg Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val60 65 70CTG CTA GAG TAT GGT AGT CCA AAA ATT AAA TCC CTA GCA ATT AGC TTT 593Leu Leu Glu Tyr Gly Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe75 80 85TTA ACA GAA CTT TTT CAG CTT GGA GGA CTA CCA GCA CAA CCA GCT AGC 641Leu Thr Glu Leu Phe Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser90 95 100ACT TTT TTC AGC TCA TTT TTG GAA TTA TTA AAA CAC CTT GTA GAA ATG 689Thr Phe Phe Ser Ser Phe Leu Glu Leu Leu Lys His Leu Val Glu Met105 110 115GAT ACT GAC CAA TTG AAA CTC TAT GAA GAG CCA TTA TCA AAG CTG ATA 737Asp Thr Asp Gln Leu Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile120 125 130 135AAG ACA CTA TTT CCC TTT GAA GCA GAA GCT TAT AGA AAT ATT GAA CCT 785Lys Thr Leu Phe Pro Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro140 145 150GTC TAT TTA AAT ATG CTG CTG GAA AAA CTC TGT GTC ATG TTT GAA GAC 833Val Tyr Leu Asn Met Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp155 160 165GGT GTG CTC ATG CGG CTT AAG TCT GAT TTG CTA AAA GCA GCT TTG TGC 881Gly Val Leu Met Arg Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys170 175 180CAT TTA CTG CAG TAT TTC CTT AAA TTT GTG CCA GCT GGG TAT GAA TCT 929His Leu Leu Gln Tyr Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser185 190 195GCT TTA CAA GTC AGG AAG GTC TAT GTG AGA AAT ATT TGT AAA GCT CTT 977Ala Leu Gln Val Arg Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu200 205 210 215TTG GAT GTG CTT GGA ATT GAG GTA GAT GCA GAG TAC TTG TTG GGC CCA 1025Leu Asp Val Leu Gly Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro220 225 230CTT TAT GCA GCT TTG AAA ATG GAA AGT ATG GAA ATC ATT GAG GAG ATT 1073Leu Tyr Ala Ala Leu Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile235 240 245CAA TGC CAA ACT CAA CAG GAA AAC CTC AGC AGT AAT AGT GAT GGA ATA 1121Gln Cys Gln Thr Gln Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile250 255 260TCA CCC AAA AGG CGT CGT CTC AGC TCG TCT CTA AAC CCT TCT AAA AGA 1169Ser Pro Lys Arg Arg Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg265 270 275GCA CCA AAA CAG ACT GAG GAA ATT AAA CAT GTG GAC ATG AAC CAA AAG 1217Ala Pro Lys Gln Thr Glu Glu Ile Lys His Val Asp Met Asn Gln Lys280 285 290 295AGC ATA TTA TGG AGT GCA CTG AAA CAG AAA GCT GAA TCC CTT CAG ATT 1265Ser Ile Leu Trp Ser Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile300 305 310TCC CTT GAA TAC AGT GGC CTA AAG AAT CCT GTT ATT GAG ATG TTA GAA 1313Ser Leu Glu Tyr Ser Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu315 320 325GGA ATT GCT GTT GTC TTA CAA CTG ACT GCT CTG TGT ACT GTT CAT TGT 1361Gly Ile Ala Val Val Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys330 335 340TCT CAT CAA AAC ATG AAC TGC CGT ACT TTC AAG GAC TGT CAA CAT AAA 1409Ser His Gln Asn Met Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys345 350 355TCC AAG AAG AAA CCT TCT GTA GTG ATA ACT TGG ATG TCA TTG GAT TTT 1457Ser Lys Lys Lys Pro Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe360 365 370 375TAC ACA ACA GTG CTT AAG AGC TGT AGA AGG TTG TTA GAA TCT GTT CAG 1505Tyr Thr Thr Val Leu Lys Ser Cys Arg Arg Leu Leu Glu Ser Val Gln380 385 390AAA CGG ACT GGA GGC AAC ATT GAT AAG GTG GTG AAA ATT TAT GAT GCT 1553Lys Arg Thr Gly Gly Asn Ile Asp Lys Val Val Lys Ile Tyr Asp Ala395 400 405TTG ATT TAT ATG CAA GTA AAC AGT TCA TTT GAA GAT CAT ATC CTG GAA 1601Leu Ile Tyr Met Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu Glu410 415 420GAT TTA TGT GGA ATG CTC TCA CTT CCA TGG ATT TAT TCC CAT TCT GAT 1649Asp Leu Cys Gly Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser Asp425 430 435GAT GGC TGT TTA AAG TTG ACC ACA TTT GCC GCT AAT CTT CTA ACA TTA 1697Asp Gly Cys Leu Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr Leu440 445 450 455AGC TGT AGG ATT TCA GAT AGC TAT TCA CCA CAG GCA CAA TCA CGA TGT 1745Ser Cys Arg Ile Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg Cys460 465 470GTG TTT CTT CTG ACT CTG TTT CCA AGA AGA ATA TTC CTT GAG TGG AGA 1793Val Phe Leu Leu Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp Arg475 480 485ACA GCA GTT TAC AAC TGG GCC CTG CAG AGC TCC CAT GAA GTA ATC CGG 1841Thr Ala Val Tyr Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile Arg490 495 500GCT AGT TGT GTT AGT GGA TTT TTT ATC TTA TTG CAG CAG CAG AAT TCT 1889Ala Ser Cys Val Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn Ser505 510 515TGT AAC AGA GTT CCC AAG ATT CTT ATA GAT AAA GTC AAA GAT GAT TCT 1937Cys Asn Arg Val Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp Ser520 525 530 535GAC ATT GTC AAG AAA GAA TTT GCT TCT ATA CTT GGT CAA CTT GTC TGT 1985Asp Ile Val Lys Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val Cys540 545 550ACT CTT CAC GGC ATG TTT TAT CTG ACA AGT TCT TTA ACA GAA CCT TTC 2033Thr Leu His Gly Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro Phe555 560 565TCT GAA CAC GGA CAT GTG GAC CTC TTC TGT AGG AAC TTG AAA GCC ACT 2081Ser Glu His Gly His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala Thr570 575 580TCT CAA CAT GAA TGT TCA TCT TCT CAA CTA AAA GCT TCT GTC TGC AAG 2129Ser Gln His Glu Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys Lys585 590 595CCA TTC CTT TTC CTA CTG AAA AAA AAA ATA CCT AGT CCA GTA AAA CTT 2177Pro Phe Leu Phe Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys Leu600 605 610 615GCT TTC ATA GAT AAT CTA CAT CAT CTT TGT AAG CAT CTT GAT TTT AGA 2225Ala Phe Ile Asp Asn Leu His His Leu Cys Lys His Leu Asp Phe Arg620 625 630GAA GAT GAA ACA GAT GTA AAA GCA GTT CTT GGA ACT TTA TTA AAT TTA 2273Glu Asp Glu Thr Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn Leu635 640 645ATG GAA GAT CCA GAC AAA GAT GTT AGA GTG GCT TTT AGT GGA AAT ATC 2321Met Glu Asp Pro Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn Ile650 655 660AAG CAC ATA TTG GAA TCC TTG GAC TCT GAA GAT GGA TTT ATA AAG GAG 2369Lys His Ile Leu Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys Glu665 670 675CTT TTT GTC TTA AGA ATG AAG GAA GCA TAT ACA CAT GCC CAA ATA TCA 2417Leu Phe Val Leu Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile Ser680 685 690 695AGA AAT AAT GAG CTG AAG GAT ACC TTG ATT CTT ACA ACA GGG GAT ATT 2465Arg Asn Asn Glu Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp Ile700 705 710GGA AGG GCC GCA AAA GGA GAT TTG GTA CCA TTT GCA CTC TTA CAC TTA 2513Gly Arg Ala Ala Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His Leu715 720 725TTG CAT TGT TTG TTA TCC AAG TCA GCA TCT GTC TCT GGA GCA GCA TAC 2561Leu His Cys Leu Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala Tyr730 735 740ACA GAA ATT AGA GCT CTG GTT GCA GCT AAA AGT GTT AAA CTG CAA AGT 2609Thr Glu Ile Arg Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln Ser745 750 755TTT TTC AGC CAG TAT AAG AAA CCC ATC TGT CAG TTT TTG GTA GAA TCC 2657Phe Phe Ser Gln Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu Ser760 765 770 775CTT CAC TCT AGT CAG ATG ACA GCA CTT CCG AAT ACT CCA TGC CAG AAT 2705Leu His Ser Ser Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln Asn780 785 790GCT GAC GTG CGA AAA CAA GAT GTG GCT CAC CAG AGA GAA ATG GCT TTA 2753Ala Asp Val Arg Lys Gln Asp Val Ala His Gln Arg Glu Met Ala Leu795 800 805AAT ACG TTG TCT GAA ATT GCC AAC GTT TTC GAC TTT CCT GAT CTT AAT 2801Asn Thr Leu Ser Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu Asn810 815 820CGT TTT CTT ACT AGG ACA TTA CAA GTT CTA CTA CCT GAT CTT GCT GCC 2849Arg Phe Leu Thr Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala Ala825 830 835AAA GCA AGC CCT GCA GCT TCT GCT CTC ATT CGA ACT TTA GGA AAA CAA 2897Lys Ala Ser Pro Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys Gln840 845 850 855TTA AAT GTC AAT CGT AGA GAG ATT TTA ATA AAC AAC TTC AAA TAT ATT 2945Leu Asn Val Asn Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr Ile860 865 870TTT TCT CAT TTG GTC TGT TCT TGT TCC AAA GAT GAA TTA GAA CGT GCC 2993Phe Ser His Leu Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg Ala875 880 885CTT CAT TAT CTG AAG AAT GAA ACA GAA ATT GAA CTG GGG AGC CTG TTG 3041Leu His Tyr Leu Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu Leu890 895 900AGA CAA GAT TTC CAA GGA TTG CAT AAT GAA TTA TTG CTG CGT ATT GGA 3089Arg Gln Asp Phe Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile Gly905 910 915GAA CAC TAT CAA CAG GTT TTT AAT GGT TTG TCA ATA CTT GCC TCA TTT 3137Glu His Tyr Gln Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser Phe920 925 930 935GCA TCC AGT GAT GAT CCA TAT CAG GGC CCG AGA GAT ATC ATA TCA CCT 3185Ala Ser Ser Asp Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser Pro940 945 950GAA CTG ATG GCT GAT TAT TTA CAA CCC AAA TTG TTG GGC ATT TTG GCT 3233Glu Leu Met Ala Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu Ala955 960 965TTT TTT AAC ATG CAG TTA CTG AGC TCT AGT GTT GGC ATT GAA GAT AAG 3281Phe Phe Asn Met Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp Lys970 975 980AAA ATG GCC TTG AAC AGT TTG ATG TCT TTG ATG AAG TTA ATG GGA CCC 3329Lys Met Ala Leu Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly Pro985 990 995AAA CAT GTC AGT TCT GTG AGG GTG AAG ATG ATG ACC ACA CTG AGA ACT 3377Lys His Val Ser Ser Val Arg Val Lys Met Met Thr Thr Leu Arg Thr01015GGC CTT CGA TTC AAG GAT GAT TTT CCT GAA TTG TGT TGC AGA GCT TGG 3425Gly Leu Arg Phe Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala Trp0GAC TGC TTT GTT CGC TGC CTG GAT CAT GCT TGT CTG GGC TCC CTT CTC 3473Asp Cys Phe Val Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu Leu5AGT CAT GTA ATA GTA GCT TTG TTA CCT CTT ATA CAC ATC CAG CCT AAA 3521Ser His Val Ile Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro Lys0GAA ACT GCA GCT ATC TTC CAC TAC CTC ATA ATT GAA AAC AGG GAT GCT 3569Glu Thr Ala Ala Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp Ala5GTG CAA GAT TTT CTT CAT GAA ATA TAT TTT TTA CCT GAT CAT CCA GAA 3617Val Gln Asp Phe Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro Glu01095TTA AAA AAG ATA AAA GCC GTT CTC CAG GAA TAC AGA AAG GAG ACC TCT 3665Leu Lys Lys Ile Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr Ser0GAG AGC ACT GAT CTT CAG ACA ACT CTT CAG CTC TCT ATG AAG GCC ATT 3713Glu Ser Thr Asp Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala Ile5CAA CAT GAA AAT GTC GAT GTT CGT ATT CAT GCT CTT ACA AGC TTG AAG 3761Gln His Glu Asn Val Asp Val Arg Ile His Ala Leu Thr Ser Leu Lys0GAA ACC TTG TAT AAA AAT CAG GAA AAA CTG ATA AAG TAT GCA ACA GAC 3809Glu Thr Leu Tyr Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr Asp5AGT GAA ACA GTA GAA CCT ATT ATC TCA CAG TTG GTG ACA GTG CTT TTG 3857Ser Glu Thr Val Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu Leu01175AAA GGT TGC CAA GAT GCA AAC TCT CAA GCT CGG TTG CTC TGT GGG GAA 3905Lys Gly Cys Gln Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly Glu0TGT TTA GGG GAA TTG GGG GCG ATA GAT CCA GGT CGA TTA GAT TTC TCA 3953Cys Leu Gly Glu Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe Ser5ACA ACT GAA ACT CAA GGA AAA GAT TTT ACA TTT GTG ACT GGA GTA GAA 4001Thr Thr Glu Thr Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val Glu0GAT TCA AGC TTT GCC TAT GGA TTA TTG ATG GAG CTA ACA AGA GCT TAC 4049Asp Ser Ser Phe Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala Tyr5CTT GCG TAT GCT GAT AAT AGC CGA GCT CCA GAT TCA GCT GCC TAT GCC 4097Leu Ala Tyr Ala Asp Asn Ser Arg Ala Pro Asp Ser Ala Ala Tyr Ala01255ATT CAG GAG TTG CTT TCT ATT TAT GAC TGT AGA GAG ATG GAG ACC AAC 4145Ile Gln Glu Leu Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr Asn0GGC CCA GGT CAC CAA TTG TGG AGG AGA TTT CCT GAG CAT GTT CGG GAA 4193Gly Pro Gly His Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg Glu5ATA CTA GAA CCT CAT CTA AAT ACC AGA TAC AAG AGT TCT CAG AAG TCA 4241Ile Leu Glu Pro His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys Ser0ACC GAT TGG TCT GGA GTA AAG AAG CCA ATT TAC TTA AGT AAA TTG GGT 4289Thr Asp Trp Ser Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu Gly5AGT AAC TTT GCA GAA TGG TCA GCA TCT TGG GCA GGT TAT CTT ATT ACA 4337Ser Asn Phe Ala Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile Thr01335AAG GTT CGA CAT GAT CTT GCC AGT AAA ATT TTC ACC TGC TGT AGC ATT 4385Lys Val Arg His Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser Ile0ATG ATG AAG CAT GAT TTC AAA GTG ACC ATC TAT CTT CTT CCA CAT ATT 4433Met Met Lys His Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His Ile5CTG GTG TAT GTC TTA CTG GGT TGT AAT CAA GAA GAT CAG CAG GAG GTT 4481Leu Val Tyr Val Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu Val0TAT GCA GAA ATT ATG GCA GTT CTA AAG CAT GAC GAT CAG CAT ACC ATA 4529Tyr Ala Glu Ile Met Ala Val Leu Lys His Asp Asp Gln His Thr Ile5AAT ACC CAA GAC ATT GCA TCT GAT CTG TGT CAA CTC AGT ACA CAG ACT 4577Asn Thr Gln Asp Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln Thr01415GTG TTC TCC ATG CTT GAC CAT CTC ACA CAG TGG GCA AGG CAC AAA TTT 4625Val Phe Ser Met Leu Asp His Leu Thr Gln Trp Ala Arg His Lys Phe0CAG GCA CTG AAA GCT GAG AAA TGT CCA CAC AGC AAA TCA AAC AGA AAT 4673Gln Ala Leu Lys Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg Asn5AAG GTA GAC TCA ATG GTA TCT ACT GTG GAT TAT GAA GAC TAT CAG AGT 4721Lys Val Asp Ser Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln Ser0GTA ACC CGT TTT CTA GAC CTC ATA CCC CAG GAT ACT CTG GCA GTA GCT 4769Val Thr Arg Phe Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val Ala5TCC TTT CGC TCC AAA GCA TAC ACA CGA GCT GTA ATG CAC TTT GAA TCA 4817Ser Phe Arg Ser Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu Ser01495TTT ATT ACA GAA AAG AAG CAA AAT ATT CAG GAA CAT CTT GGA TTT TTA 4865Phe Ile Thr Glu Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe Leu0CAG AAA TTG TAT GCT GCT ATG CAT GAA CCT GAT GGA GTG TCC GGA GTC 4913Gln Lys Leu Tyr Ala Ala Met His Glu Pro Asp Gly Val Ser Gly Val5AGT GCA ATT AGA AAG GCA GAA CCA TCT CTA AAA GAA CAG ATC CTT GAA 4961Ser Ala Ile Arg Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu Glu0CAT GAA AGC CTT GGC TTG CTG AGG GAT GCC ACT GCT TGT TAT GAC AGG 5009His Glu Ser Leu Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp Arg5GCT ATT CAG CTA GAA CCA GAC CAG ATC ATT CAT TAC CAT GGT GTA GTA 5057Ala Ile Gln Leu Glu Pro Asp Gln Ile Ile His Tyr His Gly Val Val01575AAG TCC ATG TTA GGT CTT GGT CAG CTG TCT ACT GTT ATC ACT CAG GTG 5105Lys Ser Met Leu Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln Val0AAT GGA GTG CAT GCT AAC AGG TCC GAG TGG ACA GAT GAA TTA AAC ACG 5153Asn Gly Val His Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn Thr5TAC AGA GTG GAA GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG GAA 5201Tyr Arg Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu0AAC TAT TTG GCA GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA CTG 5249Asn Tyr Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu5GGA CAG CTA TTA TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT TAT 5297Gly Gln Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr01655GAC TCA CTG AAA CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA GCT 5345Asp Ser Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Set Ala0GCA AGC TTT GAA AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT GTG 5393Ala Ser Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val5AGA TTG CAC ATG TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT TTC 5441Arg Leu His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe0CAG CAT TCT CCA GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG GTA 5489Gln His Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val5GCT CGA CTA GAA ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT ATC 5537Ala Arg Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile01735CTG GCT CTC CGG AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT TAC 5585Leu Ala Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr0AAT GAA ATG GTT GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT AGA 5633Asn Glu Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg5AAG GCT GGT CAC CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA GGG 5681Lys Ala Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly0GAA TCA CGA CTC GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC TGG 5729Glu Ser Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp5TCC AAG GGT GAT GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT GTT 5777Ser Lys Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val01815GAA TTA TGT TTT CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC ATG 5825Glu Leu Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met0TTA ATC CAT GGT CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA GAA 5873Leu Ile His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu5ACA GCT AAC TTT GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT GTG 5921Thr Ala Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val0ACC GCG TGC CTG CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC AAG 5969Thr Ala Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys5TAC TAT GAC AAA TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA AAG 6017Tyr Tyr Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys01895CAA GGT GAT CTC ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT CTA 6065Gln Gly Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu0CAA TAT GGA AAT CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA ACT 6113Gln Tyr Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr5CTA TGG CTT GAT TAT GGT ACA AAG GCA TAT GAA TGG GAA AAA GCT GGC 6161Leu Trp Leu Asp Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala Gly0CGC TCC GAT CGT GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC AAG 6209Arg Ser Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys5GTT ATC ACA GAG CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG ACT 6257Val Ile Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr01975GCT TTT TCA CAA TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA GTT 6305Ala Phe Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val0TTT GTT GTG CTT GAT GGA AAT AAT AGC CAA GTA TTT CTA GCC TAT CCT 6353Phe Val Val Leu Asp Gly Asn Asn Ser Gln Val Phe Leu Ala Tyr Pro5CAA CAA GCA ATG TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT CCC 6401Gln Gln Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro201020152020ATG CGT GTG AAC AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT ATG 6449Met Arg Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met202520302035AAA AAA TCC TTA GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA GAT 6497Lys Lys Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp2040204520502055AAG CTT CTA GAA TTG TGC AAT AAA CCG GTG GAA ATT CTT GCT TCT CTT 6545Lys Leu Leu Glu Leu Cys Asn Lys Pro Val Glu Ile Leu Ala Ser Leu206020652070CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC TAC 6593Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr207520802085ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA CTA 6641Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu209020952100ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA GAG 6689Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu2TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA CTA 6737Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu22135AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT TTG 6785Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu2AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG ACA 6833Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr2GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA TCT 6881Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser2GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT CCT 6929Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro2ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA TGG 6977Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp2200220522102215TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA ATG 7025Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met222022252230GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT CTC 7073Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu223522402245TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT CTT 7121Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu225022552260TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT CGC 7169Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg226522702275CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG GGT 7217Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly2280228522902295CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT CAG 7265Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln230023052310CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT CTT 7313Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu231523202325GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG AAT 7361Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn233023352340GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT GAC 7409Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp234523502355ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG ACA 7457Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr2360236523702375GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA GAA 7505Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu238023852390GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT CCA 7553Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro239524002405TAT ATG TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA AGTAAAAAAA 7609Tyr MetAAAAAAAAAA AA7621(2)SEQ ID NO2的說明(i)序列特征(A)長度2409個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型蛋白(xi)序列描述SEQ ID NO2Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Lys Leu Glu Phe Ile Glu Val Thr Leu Leu Thr Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Thr Val Leu Lys Ser Cys Arg370 375 380Arg Leu Leu Glu Ser Val Gln Lys Arg Thr Gly Gly Asn Ile Asp Lys385 390 395 400Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser Ser405 410 415Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu Pro420 425 430Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe435 440 445Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser450 455 460Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro Arg465 470 475 480Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln485 490 495Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe Ile500 505 510Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu Ile515 520 525Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala Ser530 535 540Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu Thr545 550 555 560Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu Phe565 570 575Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser Gln580 585 590Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys595 600 605Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His Leu610 615 620Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala Val625 630 635 640Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val Arg645 650 655Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp Ser660 665 670Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu Ala675 680 685Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu690 695 700Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu Val705 710 715 720Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser Ala725 730 735Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala740 745 750Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile755 760 765Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala Leu770 775 780Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val Ala785 790 795 800His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn Val805 810 815Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln Val820 825 830Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu835 840 845Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile Leu850 855 860Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys Ser865 870 875 880Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr Glu885 890 895Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His Asn900 905 910Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn Gly915 920 925Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly930 935 940Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro945 950 955 960Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser Ser965 970 975Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met Ser980 985 990Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val Lys995 10001005Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro0Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp His51040Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu Pro5Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr Leu0Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile Tyr5Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu Gln0Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu51120Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg Ile5His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys0Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile Ser5Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln0Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp51200Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe5Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu0Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala5Pro Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp0Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg Arg51280Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr Arg5Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys Pro0Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser5Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser Lys0Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val Thr51360Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys Asn5Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu Lys0His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu5Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu Thr0Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro51440His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr Val5Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile Pro0Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg5Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile0Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His Glu51520Pro Asp Gly Val Ser Gly Val Ser Ala Ile Arg Lys Ala Glu Pro Ser5Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg Asp0Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile5Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln Leu0Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser Glu51600Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu5Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser0Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys5Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu0Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln51680Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu Glu5His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser Gln0Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn Ser5Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser0Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp Leu51760Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala Tyr5Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val0Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala Leu5Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu Thr0Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu Leu51840Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile5Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu Asp0Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met Val5Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val0Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln51920Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala5Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg Asn0Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr Leu5Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile0Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn Ser52000Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr Ala200520102015Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu Ile202020252030Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val Gly203520402045Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro205020552060Val Glu Ile Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys2065207020752080Gly Ser Asp Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp208520902095Leu Arg Lys Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys2Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg2Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp2Val Asn Asn Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys22160Glu Lys Gly Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu2Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe2Leu Leu Pro Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr2Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg221022152220Ser Thr Ala Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp2225223022352240Arg His Gly Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val224522502255His Val Asp Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val226022652270Pro Glu Ile Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly Met227522802285Gly Pro Met Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr229022952300Met Arg Leu Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys2305231023152320Thr Phe Leu His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly232523302335His Ser Lys Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys234023452350Ala Lys Thr His Val Leu Asp Ile Glu Gln Arg Leu Gln Gly Val Ile235523602365Lys Thr Arg Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His237023752380Val His Tyr Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln2385239023952400Met Tyr Leu Gly Trp Thr Pro Tyr Met2405(2)SEQ ID NO3的說明(i)序列特征(A)長度2835個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型cDNA(vii)直接來源(B)克隆517(ix)特征(A)姓名/符號CDS(B)位置1..2610(xi)序列描述SEQ ID NO3GTG GAA GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG GAA AAC TAT 48Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr1 5 10 15TTG GCA GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA CTG GGA CAG 96Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu Gly Gln20 25 30CTA TTA TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT TAT GAC TCA 144Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser35 40 45CTG AAA CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA GCT GCA AGC 192Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser Ala Ala Ser50 55 60TTT GAA AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT GTG AGA TTG 240Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu65 70 75 80CAC ATG TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT TTC CAG CAT 288His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe Gln His85 90 95TCT CCA GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG GTA GCT CGA 336Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg100 105 110CTA GAA ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT ATC CTG GCT 384Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala115 120 125CTC CGG AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT TAC AAT GAA 432Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu130 135 140ATG GTT GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT AGA AAG GCT 480Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala145 150 155 160GGT CAC CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA GGG GAA TCA 528Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser165 170 175CGA CTC GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC TGG TCC AAG 576Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp Ser Lys180 185 190GGT GAT GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT GTT CAA TTA 624Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val Glu Leu195 200 205TGT TTT CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC ATG TTA ATC 672Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met Leu Ile210 215 220CAT GGT CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA GAA ACA GCT 720His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu Thr Ala225 230 235 240AAC TTT GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT GTG ACC GCG 768Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val Thr Ala245 250 255TGC CTG CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC AAG TAC TAT 816Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr260 265 270GAC AAA TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA AAG CAA GGT 864Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys Gln Gly275 280 285GAT CTC ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT CTA CAA TAT 912Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu Gln Tyr290 295 300GGA AAT CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA ACT CTA TGG 960Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr Leu Trp305 310 315 320CTT GAT TAT GGT ACA AAG TCA TAT GAA TGG GAA AAA GCT GGC CGC TCC 1008Leu Asp Tyr Gly Thr Lys Ser Tyr Glu Trp Glu Lys Ala Gly Arg Ser325 330 335GAT CGT GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC AAG GTT ATC 1056Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile340 345 350ACA GAG CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG ACT GCT TTT 1104Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe355 360 365TCA CAA TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA GTT TTT GTT 1152Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val370 375 380GTC TTG ATG GAA ATA ATA GCC AAA GTA TTT CTA GCC TAT CCT CAA CAA 1200Val Leu Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln385 390 395 400GCA ATG TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT CCC ATG CGT 1248Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg405 410 415GTG AAC AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT ATG AAA AAA 1296Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met Lys Lys420 425 430TCC TTA GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA GAT AAG CTT 1344Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu435 440 445CTA GAA TTG TGC AAT AAA CCG GTT GAT GGA AGT AGT TCC ACA TTA AGC 1392Leu Glu Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser Thr Leu Ser450 455 460ATG AGC ACT CAT TTT AAA ATG CTT AAA AAG CTG GTA GAA GAA GCA ACA 1440Met Ser Thr His Phe Lys Met Leu Lys Lys Leu Val Glu Glu Ala Thr465 470 475 480TTT AGT GAA ATC CTC ATT CCT CTA CAA TCA GTC ATG ATA CCT ACA CTT 1488Phe Ser Glu Ile Leu Ile Pro Leu Gln Ser Val Met Ile Pro Thr Leu485 490 495CCA TCA ATT CTG GGT ACC CAT GCT AAC CAT GCT AGC CAT GAA CCA TTT 1536Pro Ser Ile Leu Gly Thr His Ala Asn His Ala Ser His Glu Pro Phe500 505 510CCT GGA CAT TGG GCC TAT ATT GCA GGG TTT GAT GAT ATG GTG GAA ATT 1584Pro Gly His Trp Ala Tyr Ile Ala Gly Phe Asp Asp Met Val Glu Ile515 520 525CTT GCT TCT CTT CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT 1632Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp530 535 540GGA AAG TTC TAC ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG 1680Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys545 550 555 560GAT TGT AGA CTA ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA 1728Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg565 570 575AAA GAT GCA GAG TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA 1776Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala580 585 590GTT ATT CCA CTA AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC 1824Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn595 600 605ACT GCT GGT TTG AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA 1872Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly610 615 620GTG TAT ATG ACA GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA 1920Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser625 630 635 640GCA GCT TTA TCT GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC 1968Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro645 650 655AGG CAT CCT CCT ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT 2016Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp660 665 670CCT ACA TCA TGG TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA 2064Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala675 680 685GTA ATG TCA ATG GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT 2112Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly690 695 700GAA AAT ATT CTC TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT 2160Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp705 710 715 720TTC AAT TGT CTT TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT 2208Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile725 730 735GTG CCA TTT CGC CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG 2256Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met740 745 750GGA ACA GAG GGT CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG 2304Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu755 760 765ATG CGT GAT CAG CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA 2352Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu770 775 780CAT GAT CCT CTT GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA 2400His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys785 790 795 800GCG CCA CTG AAT GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC 2448Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr805 810 815CAT GTT CTT GAC ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA 2496His Val Leu Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg820 825 830AAT AGA GTG ACA GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC 2544Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr835 840 845CTT ATA CAA GAA GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT 2592Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu850 855 860GGT TGG ACT CCA TAT ATG TGAAATGAAA TTATGTAAAA GAATATGTTA2640Gly Trp Thr Pro Tyr Met865 870ATAATCTAAA AGTAATGCAT TTGGTATGAA TCTGTGGTTG TATCTGTTCA ATTCTAAAGT 2700ACAACATAAA TTTACGTTCT CAGCAACTGT TATTTCTCTC TGATCATTAA TTATATGTAA 2760AATAATATAC ATTCAGTTAT TAAGAAATAA ACTGCTTTCT TAATAAAAAA AAAAAAAAAA 2820AAAAAAAAAA AAAAA2835(2)SEQ ID NO4的說明(i)序列特征(A)長度870個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型蛋白(xi)序列描述SEQ ID NO4Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr1 5 10 15Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu Gly Gln20 25 30Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser35 40 45Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser Ala Ala Ser50 55 60Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu65 70 75 80His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe Gln His85 90 95Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg100 105 110Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala115 120 125Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu130 135 140Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala145 150 155 160Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser165 170 175Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp Ser Lys180 185 190Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val Glu Leu195 200 205Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met Leu Ile210 215 220His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu Thr Ala225 230 235 240Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val Thr Ala245 250 255Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr260 265 270Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys Gln Gly275 280 285Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu Gln Tyr290 295 300Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr Leu Trp305 310 315 320Leu Asp Tyr Gly Thr Lys Ser Tyr Glu Trp Glu Lys Ala Gly Arg Ser325 330 335Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile340 345 350Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe355 360 365Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val370 375 380Val Leu Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln385 390 395 400Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg405 410 415Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met Lys Lys420 425 430Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu435 440 445Leu Glu Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser Thr Leu Ser450 455 460Met Ser Thr His Phe Lys Met Leu Lys Lys Leu Val Glu Glu Ala Thr465 470 475 480Phe Ser Glu Ile Leu Ile Pro Leu Gln Ser Val Met Ile Pro Thr Leu485 490 495Pro Ser Ile Leu Gly Thr His Ala Asn His Ala Ser His Glu Pro Phe500 505 510Pro Gly His Trp Ala Tyr Ile Ala Gly Phe Asp Asp Met Val Glu Ile515 520 525Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp530 535 540Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys545 550 555 560Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg565 570 575Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala580 585 590Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn595 600 605Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly610 615 620Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser625 630 635 640Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro645 650 655Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp660 665 670Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala675 680 685Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly690 695 700Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp705 710 715 720Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile725 730 735Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met740 745 750Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu755 760 765Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu770 775 780His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys785 790 795 800Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr805 810 815His Val Leu Asp Ile Glu Gln Arg Leu Gln GIy Val Ile Lys Thr Arg820 825 830Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr835 840 845Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu850 855 860Gly Trp Thr Pro Tyr Met865 870(2)SEQ ID NO5的說明(i)序列特征(A)長度33堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oDH15a(ix)特征(A)姓名/符號修飾的堿基(B)位置組(15，18，24，30)(D)其它資料在這些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO5GCAGACGGAT CCGGNWCNGA YGGNAAYHTN TAY 33(2)SEQ ID NO6的說明(i)序列特征(A)長度27個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(ix)特征(A)姓名/符號修飾的堿基(B)位置組(15，18，24)(D)其它資料在這些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO6GCAGACGGAT CCGGNWCNGA YGGNAAY27(2)SEQ ID NO7的說明(i)序列特征(A)長度30個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oDH16(ix)特征(A)姓名/符號修飾的堿基(B)位置24(D)其它資料在這些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO7GCAGACGAAT TCRCARTYRA ARTCNACRTG 30(2)SEQ ID NO8的說明(i)序列特征(A)長度41個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oDH17a(ix)特征(A)姓名/符號修飾的堿基(B)位置組(21，24，27，30)(D)其它資料在這些位置的核苷酸是肌苷。
(xi)序列描述SEQ ID NO8GCAGACGGAT CCAARTTYCC NCCNRTNYTN TAYSARTGGT T41(2)SEQ ID NO9的說明(i)序列特征(A)長度41個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oDH17b(ix)特征(A)姓名/符號修飾的堿基(B)位置組(24，27，30，33)(D)其它資料在這些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO9GCAGACGAAT CCAACCAYTS RTANARAYN GGNGGRAAYT T41(2)SEQ ID NO10的說明(i)序列特征(A)長度32個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oDH18a(ix)特征(A)姓名/符號修飾的堿基(B)位置組(15，18，21，24，30)(D)其它資料在這些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO10GCAGACGGAT CCYTNGGNYT NGGNGAYCGN CA 32(2)SEQ ID NO11的說明(i)序列特征(A)長度32個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oDH18b(ix)特征(A)姓名/符號修飾的堿基(B)位置組(15，18，21)(D)其它資料在這些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO11GCAGACGGAT CCYTNGGNYT NGGNGAYAGR CA 32(2)SEQ ID NO12的說明(i)序列特征(A)長度33個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oDH23(xi)序列描述SEQ ID NO12GACGCAGAAT TCACCAGTCA AAGAATCAAA GAG 33(2)SEQ ID NO13的說明(i)序列特征(A)長度16個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物mo3(xi)序列描述SEQ ID NO13CTACAGAGCC AAGGAG16(2)SEQ ID NO14的說明(i)序列特征(A)長度22個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物mo6(xi)序列描述SEQ ID NO14TCGAGCTATG CTACTAGTGG GC 22(2)SEQ ID NO15的說明(i)序列特征(A)長度17個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oHT9-1(xi)序列描述SEQ ID NO15CCAGTAAACT TGCTTTC 17(2)SEQ ID NO16的說明(i)序列特征(A)長度20個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oHT9-4(xi)序列描述SEQ ID NO16TTTGCGGCCC TTCCAATATC20(2)SEQ ID NO17的說明(i)序列特征(A)長度7440個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型cDNA(vii)直接來源(B)克隆MCCS1beta(ix)特征(A)姓名/符號CDS(B)位置1..7437(xi)序列描述SEQ ID NO17ATG GGT CAT GCT GTG GAA TGG CCA GTG GTC ATG AGC CGA TTT TTA AGT 48Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15CAA TTA GAT GAA CAC ATG GGA TAT TTA CAA TCA GCT CCT TTG CAG TTG 96Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30ATG AGT ATG CAA AAA TTA GAA TTT ATT GAA GTC ACT TTA TTA ACG GTT 144Met Ser Met Gln Lys Leu Glu Phe Ile Glu Val Thr Leu Leu Thr Val35 40 45CTT ACT CGT ATT ATT GCA ATT GTG TTT TTT AGA AGG CAA GAA CTC TTA 192Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60CTT TGG CAG ATA GGT TGT GTT CTG CTA GAG TAT GGT AGT CCA AAA ATT 240Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80AAA TCC CTA GCA ATT AGC TTT TTA ACA GAA CTT TTT CAG CTT GGA GGA 288Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95CTA CCA GCA CAA CCA GCT AGC ACT TTT TTC AGC TCA TTT TTG GAA TTA 336Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110TTA AAA CAC CTT GTA GAA ATG GAT ACT GAC CAA TTG AAA CTC TAT GAA 384Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125GAG CCA TTA TCA AAG CTG ATA AAG ACA CTA TTT CCC TTT GAA GCA GAA 432Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140GCT TAT AGA AAT ATT GAA CCT GTC TAT TTA AAT ATG CTG CTG GAA AAA 480Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160CTC TGT GTC ATG TTT GAA GAC GGT GTG CTC ATG CGG CTT AAG TCT GAT 528Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175TTG CTA AAA GCA GCT TTG TGC CAT TTA CTG CAG TAT TTC CTT AAA TTT 576Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190GTG CCA GCT GGG TAT GAA TCT GCT TTA CAA GTC AGG AAG GTC TAT GTG 624Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205AGA AAT ATT TGT AAA GCT CTT TTG GAT GTG CTT GGA ATT GAG GTA GAT 672Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220GCA GAG TAC TTG TTG GGC CCA CTT TAT GCA GCT TTG AAA ATG GAA AGT 720Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240ATG GAA ATC ATT GAG GAG ATT CAA TGC CAA ACT CAA CAG GAA AAC CTC 768Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255AGC AGT AAT AGT GAT GGA ATA TCA CCC AAA AGG CGT CGT CTC AGC TCG 816Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270TCT CTA AAC CCT TCT AAA AGA GCA CCA AAA CAG ACT GAG GAA ATT AAA 864Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285CAT GTG GAC ATG AAC CAA AAG AGC ATA TTA TGG AGT GCA CTG AAA CAG 912His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300AAA GCT GAA TCC CTT CAG ATT TCC CTT GAA TAC AGT GGC CTA AAG AAT 960Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320CCT GTT ATT GAG ATG TTA GAA GGA ATT GCT GTT GTC TTA CAA CTG ACT 1008Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335GCT CTG TGT ACT GTT CAT TGT TCT CAT CAA AAC ATG AAC TGC CGT ACT 1056Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350TTC AAG GAC TGT CAA CAT AAA TCC AAG AAG AAA CCT TCT GTA GTG ATA 1104Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365ACT TGG ATG TCA TTG GAT TTT TAC ACA ACA GTG CTT AAG AGC TGT AGA 1152Thr Trp Met Ser Leu Asp Phe Tyr Thr Thr Val Leu Lys Ser Cys Arg370 375 380AGG TTG TTA GAA TCT GTT CAG AAA CGG ACT GGA GGC AAC ATT GAT AAG 1200Arg Leu Leu Glu Ser Val Gln Lys Arg Thr Gly Gly Asn Ile Asp Lys385 390 395 400GTG GTG AAA ATT TAT GAT GCT TTG ATT TAT ATG CAA GTA AAC AGT TCA 1248Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser Ser405 410 415TTT GAA GAT CAT ATC CTG GAA GAT TTA TGT GGA ATG CTC TCA CTT CCA 1296Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu Pro420 425 430TGG ATT TAT TCC CAT TCT GAT GAT GGC TGT TTA AAG TTG ACC ACA TTT 1344Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe435 440 445GCC GCT AAT CTT CTA ACA TTA AGC TGT AGG ATT TCA GAT AGC TAT TCA 1392Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser450 455 460CCA CAG GCA CAA TCA CGA TGT GTG TTT CTT CTG ACT CTG TTT CCA AGA 1440Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro Arg465 470 475 480AGA ATA TTC CTT GAG TGG AGA ACA GCA GTT TAC AAC TGG GCC CTG CAG 1488Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln485 490 495AGC TCC CAT GAA GTA ATC CGG GCT AGT TGT GTT AGT GGA TTT TTT ATC 1536Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe Ile500 505 510TTA TTG CAG CAG CAG AAT TCT TGT AAC AGA GTT CCC AAG ATT CTT ATA 1584Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu Ile515 520 525GAT AAA GTC AAA GAT GAT TCT GAC ATT GTC AAG AAA GAA TTT GCT TCT 1632Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala Ser530 535 540ATA CTT GGT CAA CTT GTC TGT ACT CTT CAC GGC ATG TTT TAT CTG ACA 1680Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu Thr545 550 555 560AGT TCT TTA ACA GAA CCT TTC TCT GAA CAC GGA CAT GTG GAC CTC TTC 1728Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu Phe565 570 575TGT AGG AAC TTG AAA GCC ACT TCT CAA CAT GAA TGT TCA TCT TCT CAA 1776Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser Gln580 585 590CTA AAA GCT TCT GTC TGC AAG CCA TTC CTT TTC CTA CTG AAA AAA AAA 1824Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys595 600 605ATA CCT AGT CCA GTA AAA CTT GCT TTC ATA GAT AAT CTA CAT CAT CTT 1872Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His Leu610 615 620TGT AAG CAT CTT GAT TTT AGA GAA GAT GAA ACA GAT GTA AAA GCA GTT 1920Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala Val625 630 635 640CTT GGA ACT TTA TTA AAT TTA ATG GAA GAT CCA GAC AAA GAT GTT AGA 1968Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val Arg645 650 655GTG GCT TTT AGT GGA AAT ATC AAG CAC ATA TTG GAA TCC TTG GAC TCT 2016Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp Ser660 665 670GAA GAT GGA TTT ATA AAG GAG CTT TTT GTC TTA AGA ATG AAG GAA GCA 2064Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu Ala675 680 685TAT ACA CAT GCC CAA ATA TCA AGA AAT AAT GAG CTG AAG GAT ACC TTG 2112Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu690 695 700ATT CTT ACA ACA GGG GAT ATT GGA AGG GCC GCA AAA GGA GAT TTG GTA 2160Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu Val705 710 715 720CCA TTT GCA CTC TTA CAC TTA TTG CAT TGT TTG TTA TCC AAG TCA GCA 2208Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser Ala725 730 735TCT GTC TCT GGA GCA GCA TAC ACA GAA ATT AGA GCT CTG GTT GCA GCT 2256Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala740 745 750AAA AGT GTT AAA CTG CAA AGT TTT TTC AGC CAG TAT AAG AAA CCC ATC 2304Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile755 760 765TGT CAG TTT TTG GTA GAA TCC CTT CAC TCT AGT CAG ATG ACA GCA CTT 2352Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala Leu770 775 780CCG AAT ACT CCA TGC CAG AAT GCT GAC GTG CGA AAA CAA GAT GTG GCT 2400Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val Ala785 790 795 800CAC CAG AGA GAA ATG GCT TTA AAT ACG TTG TCT GAA ATT GCC AAC GTT 2448His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn Val805 810 815TTC GAC TTT CCT GAT CTT AAT CGT TTT CTT ACT AGG ACA TTA CAA GTT 2496Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln Val820 825 830CTA CTA CCT GAT CTT GCT GCC AAA GCA AGC CCT GCA GCT TCT GCT CTC 2544Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu835 840 845ATT CGA ACT TTA GGA AAA CAA TTA AAT GTC AAT CGT AGA GAG ATT TTA 2592Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile Leu850 855 860ATA AAC AAC TTC AAA TAT ATT TTT TCT CAT TTG GTC TGT TCT TGT TCC 2640Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys Ser865 870 875 880AAA GAT GAA TTA GAA CGT GCC CTT CAT TAT CTG AAG AAT GAA ACA GAA 2688Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr Glu885 890 895ATT GAA CTG GGG AGC CTG TTG AGA CAA GAT TTC CAA GGA TTG CAT AAT 2736Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His Asn900 905 910GAA TTA TTG CTG CGT ATT GGA GAA CAC TAT CAA CAG GTT TTT AAT GGT 2784Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn Gly915 920 925TTG TCA ATA CTT GCC TCA TTT GCA TCC AGT GAT GAT CCA TAT CAG GGC 2832Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly930 935 940CCG AGA GAT ATC ATA TCA CCT GAA CTG ATG GCT GAT TAT TTA CAA CCC 2880Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro945 950 955 960AAA TTG TTG GGC ATT TTG GCT TTT TTT AAC ATG CAG TTA CTG AGC TCT 2928Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser Ser965 970 975AGT GTT GGC ATT GAA GAT AAG AAA ATG GCC TTG AAC AGT TTG ATG TCT 2976Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met Ser980 985 990TTG ATG AAG TTA ATG GGA CCC AAA CAT GTC AGT TCT GTG AGG GTG AAG 3024Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val Lys995 10001005ATG ATG ACC ACA CTG AGA ACT GGC CTT CGA TTC AAG GAT GAT TTT CCT 3072Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro0GAA TTG TGT TGC AGA GCT TGG GAC TGC TTT GTT CGC TGC CTG GAT CAT 3120Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp His51040GCT TGT CTG GGC TCC CTT CTC AGT CAT GTA ATA GTA GCT TTG TTA CCT 3168Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu Pro5CTT ATA CAC ATC CAG CCT AAA GAA ACT GCA GCT ATC TTC CAC TAC CTC 3216Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr Leu0ATA ATT GAA AAC AGG GAT GCT GTG CAA GAT TTT CTT CAT GAA ATA TAT 3264Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile Tyr5TTT TTA CCT GAT CAT CCA GAA TTA AAA AAG ATA AAA GCC GTT CTC CAG 3312Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu Gln0GAA TAC AGA AAG GAG ACC TCT GAG AGC ACT GAT CTT CAG ACA ACT CTT 3360Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu51120CAG CTC TCT ATG AAG GCC ATT CAA CAT GAA AAT GTC GAT GTT CGT ATT 3408Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg Ile5CAT GCT CTT ACA AGC TTG AAG GAA ACC TTG TAT AAA AAT CAG GAA AAA 3456His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys0CTG ATA AAG TAT GCA ACA GAC AGT GAA ACA GTA GAA CCT ATT ATC TCA 3504Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile Ser5CAG TTG GTG ACA GTG CTT TTG AAA GGT TGC CAA GAT GCA AAC TCT CAA 3552Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln0GCT CGG TTG CTC TGT GGG GAA TGT TTA GGG GAA TTG GGG GCG ATA GAT 3600Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp51200CCA GGT CGA TTA GAT TTC TCA ACA ACT GAA ACT CAA GGA AAA GAT TTT 3648Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe5ACA TTT GTG ACT GGA GTA GAA GAT TCA AGC TTT GCC TAT GGA TTA TTG 3696Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu0ATG GAG CTA ACA AGA GCT TAC CTT GCG TAT GCT GAT AAT AGC CGA GCT 3744Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala5CCA GAT TCA GCT GCC TAT GCC ATT CAG GAG TTG CTT TCT ATT TAT GAC 3792Pro Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp0TGT AGA GAG ATG GAG ACC AAC GGC CCA GGT CAC CAA TTG TGG AGG AGA 3840Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg Arg51280TTT CCT GAG CAT GTT CGG GAA ATA CTA GAA CCT CAT CTA AAT ACC AGA 3888Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr Arg5TAC AAG AGT TCT CAG AAG TCA ACC GAT TGG TCT GGA GTA AAG AAG CCA 3936Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys Pro0ATT TAC TTA AGT AAA TTG GGT AGT AAC TTT GCA GAA TGG TCA GCA TCT 3984Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser5TGG GCA GGT TAT CTT ATT ACA AAG GTT CGA CAT GAT CTT GCC AGT AAA 4032Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser Lys0ATT TTC ACC TGC TGT AGC ATT ATG ATG AAG CAT GAT TTC AAA GTG ACC 4080Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val Thr51360ATC TAT CTT CTT CCA CAT ATT CTG GTG TAT GTC TTA CTG GGT TGT AAT 4128Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys Asn5CAA GAA GAT CAG CAG GAG GTT TAT GCA GAA ATT ATG GCA GTT CTA AAG 4176Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu Lys0CAT GAC GAT CAG CAT ACC ATA AAT ACC CAA GAC ATT GCA TCT GAT CTG 4224His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu5TGT CAA CTC AGT ACA CAG ACT GTG TTC TCC ATG CTT GAC CAT CTC ACA 4272Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu Thr0CAG TGG GCA AGG CAC AAA TTT CAG GCA CTG AAA GCT GAG AAA TGT CCA 4320Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro51440CAC AGC AAA TCA AAC AGA AAT AAG GTA GAC TCA ATG GTA TCT ACT GTG 4368His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr Val5GAT TAT GAA GAC TAT CAG AGT GTA ACC CGT TTT CTA GAC CTC ATA CCC 4416Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile Pro0CAG GAT ACT CTG GCA GTA GCT TCC TTT CGC TCC AAA GCA TAC ACA CGA 4464Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg5GCT GTA ATG CAC TTT GAA TCA TTT ATT ACA GAA AAG AAG CAA AAT ATT 4512Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile0CAG GAA CAT CTT GGA TTT TTA CAG AAA TTG TAT GCT GCT ATG CAT GAA 4560Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His Glu51520CCT GAT GGA GTG TCC GGA GTC AGT GCA ATT AGA AAG GCA GAA CCA TCT 4608Pro Asp Gly Val Ser Gly Val Ser Ala Ile Arg Lys Ala Glu Pro Ser5CTA AAA GAA CAG ATC CTT GAA CAT GAA AGC CTT GGC TTG CTG AGG GAT 4656Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg Asp0GCC ACT GCT TGT TAT GAC AGG GCT ATT CAG CTA GAA CCA GAC CAG ATC 4704Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile5ATT CAT TAC CAT GGT GTA GTA AAG TCC ATG TTA GGT CTT GGT CAG CTG 4752Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln Leu0TCT ACT GTT ATC ACT CAG GTG AAT GGA GTG CAT GCT AAC AGG TCC GAG 4800Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser Glu51600TGG ACA GAT GAA TTA AAC ACG TAC AGA GTG GAA GCA GCT TGG AAA TTG 4848Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu5TCA CAG TGG GAT TTG GTG GAA AAC TAT TTG GCA GCA GAT GGA AAA TCT 4896Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser0ACA ACA TGG AGT GTC AGA CTG GGA CAG CTA TTA TTA TCA GCC AAA AAA 4944Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys5AGA GAT ATC ACA GCT TTT TAT GAC TCA CTG AAA CTA GTG AGA GCA GAA 4992Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu0CAA ATT GTA CCT CTT TCA GCT GCA AGC TTT GAA AGA GGC TCC TAC CAA 5040Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln51680CGA GGA TAT GAA TAT ATT GTG AGA TTG CAC ATG TTA TGT GAG TTG GAG 5088Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu Glu5CAT AGC ATC AAA CCA CTT TTC CAG CAT TCT CCA GGT GAC AGT TCT CAA 5136His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser Gln0GAA GAT TCT CTA AAC TGG GTA GCT CGA CTA GAA ATG ACC CAG AAT TCC 5184Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn Ser5TAC AGA GCC AAG GAG CCT ATC CTG GCT CTC CGG AGG GCT TTA CTA AGC 5232Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser0CTC AAC AAA AGA CCA GAT TAC AAT GAA ATG GTT GGA GAA TGC TGG CTG 5280Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp Leu51760CAG AGT GCC AGG GTA GCT AGA AAG GCT GGT CAC CAC CAG ACA GCC TAC 5328Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala Tyr5AAT GCT CTC CTT AAT GCA GGG GAA TCA CGA CTC GCT GAA CTG TAC GTG 5376Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val0GAA AGG GCA AAG TGG CTC TGG TCC AAG GGT GAT GTT CAC CAG GCA CTA 5424Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala Leu5ATT GTT CTT CAA AAA GGT GTT GAA TTA TGT TTT CCT GAA AAT GAA ACC 5472Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu Thr0CCA CCT GAG GGT AAG AAC ATG TTA ATC CAT GGT CGA GCT ATG CTA CTA 5520Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu Leu51840GTG GGC CGA TTT ATG GAA GAA ACA GCT AAC TTT GAA AGC AAT GCA ATT 5568Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile5ATG AAA AAA TAT AAG GAT GTG ACC GCG TGC CTG CCA GAA TGG GAG GAT 5616Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu Asp0GGG CAT TTT TAC CTT GCC AAG TAC TAT GAC AAA TTG ATG CCC ATG GTC 5664Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met Val5ACA GAC AAC AAA ATG GAA AAG CAA GGT GAT CTC ATC CGG TAT ATA GTT 5712Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val0CTT CAT TTT GGC AGA TCT CTA CAA TAT GGA AAT CAG TTC ATA TAT CAG 5760Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln51920TCA ATG CCA CGA ATG TTA ACT CTA TGG CTT GAT TAT GGT ACA AAG GCA 5808Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala5TAT GAA TGG GAA AAA GCT GGC CGC TCC GAT CGT GTA CAA ATG AGG AAT 5856Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg Asn0GAT TTG GGT AAA ATA AAC AAG GTT ATC ACA GAG CAT ACA AAC TAT TTA 5904Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr Leu5GCT CCA TAT CAA TTT TTG ACT GCT TTT TCA CAA TTG ATC TCT CGA ATT 5952Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile0TGT CAT TCT CAC GAT GAA GTT TTT GTT GTG CTT GAT GGA AAT AAT AGC 6000Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn Ser52000CAA GTA TTT CTA GCC TAT CCT CAA CAA GCA ATG TGG ATG ATG ACA GCT 6048Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr Ala200520102015GTG TCA AAG TCA TCT TAT CCC ATG CGT GTG AAC AGA TGC AAG GAA ATC 6096Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu Ile202020252030CTC AAT AAA GCT ATT CAT ATG AAA AAA TCC TTA GAG AAG TTT GTT GGA 6144Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val Gly203520402045GAT GCA ACT CGC CTA ACA GAT AAG CTT CTA GAA TTG TGC AAT AAA CCG 6192Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro205020552060GTT GAT GGA AGT AGT TCC ACA TTA AGC ATG AGC ACT CAT TTT AAA ATG 6240Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys Met2065207020752080CTT AAA AAG CTG GTA GAA GAA GCA ACA TTT AGT GAA ATC CTC ATT CCT 6288Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile Pro208520902095CTA CAA TCA GTC ATG ATA CCT ACA CTT CCA TCA ATT CTG GGT ACC CAT 6336Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr His2GCT AAC CAT GCT AGC CAT GAA CCA TTT CCT GGA CAT TGG GCC TAT ATT 6384Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr Ile2GCA GGG TTT GAT GAT ATG GTG GAA ATT CTT GCT TCT CTT CAG AAA CCA 6432Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys Pro2AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC TAC ATC ATG ATG 6480Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met22160TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA CTA ATG GAA TTC 6528Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu Phe2AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA GAG TCT CGT AGA 6576Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg2AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA CTA AAT GAT GAA 6624Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu2TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT TTG AGA CCT ATT 6672Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro Ile221022152220CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG ACA GGA AAA GAA 6720Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys Glu2225223022352240CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA TCT GAA AAA CTC 6768Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu224522502255AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT CCT ATT TTT CAT 6816Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe His226022652270GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA TGG TAC AGT AGT 6864Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser227522802285AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA ATG GTT GGT TAT 6912Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly Tyr229022952300ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT CTC TTT GAT TCT 6960Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp Ser2305231023152320TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT CTT TTC AAT AAG 7005Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn Lys232523302335GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT CGC CTG ACT CAT 7056Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr His234023452350AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG GGT CTT TTT CGA 7204Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg235523602365AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT CAG CGA GAG CCT 7152Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro237023752380TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT CTT GTG GAA TGG 7200Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp2385239023952400AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG AAT GAA ACT GGA 7248Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr Gly240524102415GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT GAC ATT GAG CAG 7296Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu Gln242024252430CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG ACA GGA CTG CCG 7344Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu Pro243524402445TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA GAA GCT ACT GAT 7392Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr Asp245024552460GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT CCA TAT ATG 7437Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met246524702475TGA 7440(2)SEQ ID NO18的說明(i)序列特征(A)長度2479個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型蛋白(xi)序列描述SEQ ID NO18Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Lys Leu Glu Phe Ile Glu Val Thr Leu Leu Thr Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Thr Val Leu Lys Ser Cys Arg370 375 380Arg Leu Leu Glu Ser Val Gln Lys Arg Thr Gly Gly Asn Ile Asp Lys385 390 395 400Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser Ser405 410 415Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu Pro420 425 430Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe435 440 445Ala Ala Asn Leu Leu Thr Leu Sar Cys Arg Ile Ser Asp Ser Tyr Ser450 455 460Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro Arg465 470 475 480Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln485 490 495Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe Ile500 505 510Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu Ile515 520 525Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala Ser530 535 540Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu Thr545 550 555 560Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu Phe565 570 575Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser Gln580 585 590Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys595 600 605Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His Leu610 615 620Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala Val625 630 635 640Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val Arg645 650 655Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp Ser660 665 670Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu Ala675 680 685Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu690 695 700Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu Val705 710 715 720Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser Ala725 730 735Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala740 745 750Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile755 760 765Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala Leu770 775 780Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val Ala785 790 795 800His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn Val805 810 815Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln Val820 825 830Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu835 840 845Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile Leu850 855 860Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys Ser865 870 875 880Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr Glu885 890 895Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His Asn900 905 910Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn Gly915 920 925Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly930 935 940Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro945 950 955 960Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser Ser965 970 975Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met Ser980 985 990Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val Lys995 10001005Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro0Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp His51040Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu Pro5Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr Leu0Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile Tyr5Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu Gln0Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu51120Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg Ile5His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys0Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile Ser5Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln0Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp51200Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe5Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu0Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala5Pro Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp0Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg Arg51280Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr Arg5Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys Pro0Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser5Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser Lys0Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val Thr51360Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys Asn5Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu Lys0His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu5Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu Thr0Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro51440His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr Val5Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile Pro0Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg5Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile0Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His Glu5l520Pro Asp Gly Val Ser Gly Val Ser Ala Ile Arg Lys Ala Glu Pro Ser5Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg Asp0Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile5Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln Leu0Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser Glu51600Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu5Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser0Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys5Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu0Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln51680Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu Glu5His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser Gln0Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn Ser5Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser0Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp Leu51760Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala TTr5Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val0Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala Leu5Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu Thr0Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu Leu51640Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile5Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu Asp0Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met Val5Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val0Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln51920Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala5Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg Asn0Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr Leu5Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile0Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn Ser52000Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr Ala200520102015Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu Ile202020252030Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val Gly203520402045Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro205020552060Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys Met2065207020752080Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile Pro208520902095Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr His2Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr Ile2Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys Pro2Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met22160Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu Phe2Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg2Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu2Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro Ile221022152220Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys Glu2225223022352240Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu224522502255Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe His226022652270Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser227522802285Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly Tyr229022952300Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp Ser2305231023152320Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn Lys232523302335Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr His234023452350Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg235523602365Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro237023752380Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp2385239023952400Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr Gly240524102415Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu Gln242024252430Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu Pro243524402445Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr Asp245024552460Glu Asn Leu Leu Cys Gln Met Tyr Leu G1y Trp Thr Pro Tyr Met246524702475(2)SEQ ID NO19的說明(i)序列特征(A)長度23個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物oDH26(xi)序列描述SEQ ID NO19TGGTTTCTGA GAACATTCCC TGA 23(2)SEQ ID NO20的說明(i)序列特征(A)長度9個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型肽(vii)直接來源(B)克隆FLAG標記(xi)序列描述SEQ ID NO20Met Asp Tyr Lys Asp Asp Asp Asp Lys1 5(2)SEQ ID NO21的說明(i)序列特征(A)長度20個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物279-3(xi)序列描述SEQ ID NO21TGGATGATGA CAGCTGTGTC 20(2)SEQ ID NO22的說明(i)序列特征(A)長度20個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(vii)直接來源(B)克隆引物279-6(xi)序列描述SEQ ID NO22TGTAGTCGCT GCTCAATGTC 20(2)SEQ ID NO23的說明(i)序列特征(A)長度7624個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型cDNA(ix)特征(A)姓名/符號CDS(B)位置333..7562(xi)序列描述SEQ ID NO23CTTGTGAAGA GAATGTTTTA CACTCTIGTT AGTGAAGTTT ATTCTTTAAA AGTCAATCGT60CAAGGATTTA GCAAATGAAT TAGCACTTCG GATATACTTG TTTATTTAAT ATCTTTTTTG120TTTATTTCAA AGAATTCAGT AATTGGATCA TAACGAGACT TCTGCGGATT GCAGCAACTC180CCTCCTGTCA TTTGTTACAC AAGAAAATCT GTGAAGTCAT CTGTTCATTA TTATTTCTTT240TTAAAAGCAA GAGTCCTGCT ATTTTTGGGG TACTCACAAA AGAATTATTA CAACTTTTTG300AAGACTTGGT TTACCTCCAT AGAAGAAATG TG ATG GGT CAT GCT GTG GAA TGG 353Met Gly His Ala Val Glu Trp1 5CCA GTG GTC ATG AGC CGA TTT TTA AGT CAA TTA GAT GAA CAC ATG GGA 401Pro Val Val Met Ser Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly10 15 20TAT TTA CAA TCA GCT CCT TTG CAG TTG ATG AGT ATG CAA AAT TTA GAA 449Tyr Leu Gln Set Ala Pro Leu Gln Leu Met Ser Met Gln Asn Leu Glu25 30 35TTT ATT GAA GTC ACT TTA TTA ATG GTT CTT ACT CGT ATT ATT GCA ATT 497Phe Ile Glu Val Thr Leu Leu Met Val Leu Thr Arg Ile Ile Ala Ile40 45 50 55GTG TTT TTT AGA AGG CAA GAA CTC TTA CTT TGG CAG ATA GGT TGT GTT 545Val Phe Phe Arg Arg Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val60 65 70CTG CTA GAG TAT GGT AGT CCA AAA ATT AAA TCC CTA GCA ATT AGC TTT 593Leu Leu Glu Tyr Gly Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe75 80 85TTA ACA GAA CTT TTT CAG CTT GGA GGA CTA CCA GCA CAA CCA GCT AGC 641Leu Thr Glu Leu Phe Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser90 95 100ACT TTT TTC AGC TCA TTT TTG GAA TTA TTA AAA CAC CTT GTA GAA ATG 689Thr Phe Phe Ser Ser Phe Leu Glu Leu Leu Lys His Leu Val Glu Met105 110 115GAT ACT GAC CAA TTG AAA CTC TAT GAA GAG CCA TTA TCA AAG CTG ATA 737Asp Thr Asp Gln Leu Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile120 125 130 135AAG ACA CTA TTT CCC TTT GAA GCA GAA GCT TAT AGA AAT ATT GAA CCT 785Lys Thr Leu Phe Pro Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro140 145 150GTC TAT TTA AAT ATG CTG CTG GAA AAA CTC TGT GTC ATG TTT GAA GAC 833Val Tyr Leu Asn Met Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp155 160 165GGT GTG CTC ATG CGG CTT AAG TCT GAT TTG CTA AAA GCA GCT TTG TGC 881Gly Val Leu Met Arg Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys170 175 180CAT TTA CTG CAG TAT TTC CTT AAA TTT GTG CCA GCT GGG TAT GAA TCT 929His Leu Leu Gln Tyr Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser185 190 195GCT TTA CAA GTC AGG AAG GTC TAT GTG AGA AAT ATT TGT AAA GCT CTT 977Ala Leu Gln Val Arg Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu200 205 210 215TTG GAT GTG CTT GGA ATT GAG GTA GAT GCA GAG TAC TTG TTG GGC CCA 1025Leu Asp Val Leu Gly Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro220 225 230CTT TAT GCA GCT TTG AAA ATG GAA AGT ATG GAA ATC ATT GAG GAG ATT 1073Leu Tyr Ala Ala Leu Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile235 240 245CAA TGC CAA ACT CAA CAG GAA AAC CTC AGC AGT AAT AGT GAT GGA ATA 1121Gln Cys Gln Thr Gln Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile250 255 260TCA CCC AAA AGG CGT CGT CTC AGC TCG TCT CTA AAC CCT TCT AAA AGA 1169Ser Pro Lys Arg Arg Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg265 270 275GCA CCA AAA CAG ACT GAG GAA ATT AAA CAT GTG GAC ATG AAC CAA AAG 1217Ala Pro Lys Gln Thr Glu Glu Ile Lys His Val Asp Met Asn Gln Lys280 285 290 295AGC ATA TTA TGG AGT GCA CTG AAA CAG AAA GCT GAA TCC CTT CAG ATT 1265Ser Ile Leu Trp Ser Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile300 305 310TCC CTT GAA TAC AGT GGC CTA AAG AAT CCT GTT ATT GAG ATG TTA GAA 1313Ser Leu Glu Tyr Ser Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu315 320 325GGA ATT GCT GTT GTC TTA CAA CTG ACT GCT CTG TGT ACT GTT CAT TGT 1361Gly Ile Ala Val Val Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys330 335 340TCT CAT CAA AAC ATG AAC TGC CGT ACT TTC AAG GAC TGT CAA CAT AAA 1409Ser His Gln Asn Met Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys345 350 355TCC AAG AAG AAA CCT TCT GTA GTG ATA ACT TGG ATG TCA TTG GAT TTT 1450Ser Lys Lys Lys Pro Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe360 365 370 375TAC ACA AAA GTG CTT AAG AGC TGT AGA AGT TTG TTA GAA TCT GTT CAG 1505Tyr Thr Lys Val Leu Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln380 385 390AAA CTG GAC CTG GAG GCA ACC ATT GAT AAG GTG GTG AAA ATT TAT GAT 1553Lys Leu Asp Leu Glu Ala Thr Ile Asp Lys Val Val Lys Ile Tyr Asp395 400 405GCT TTG ATT TAT ATG CAA GTA AAC AGT TCA TTT GAA GAT CAT ATC CTG 1601Ala Leu Ile Tyr Met Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu410 415 420GAA GAT TTA TGT GGA ATG CTC TCA CTT CCA TGG ATT TAT TCC CAT TCT 1645Glu Asp Leu Cys Gly Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser425 430 435GAT GAT GGC TGT TTA AAG TTG ACC ACA TTT GCC GCT AAT CTT CTA ACA 1697Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr440 445 450 455TTA AGC TGT AGG ATT TCA GAT AGC TAT TCA CCA CAG GCA CAA TCA CGA 1745Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg460 465 470TGT GTG TTT CTT CTG ACT CTG TTT CCA AGA AGA ATA TTC CTT GAG TGG 1793Cys Val Phe Leu Leu Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp475 480 485AGA ACA GCA GTT TAC AAC TGG GCC CTG CAG AGC TCC CAT GAA GTA ATC 1841Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile490 495 500CGG GCT AGT TGT GTT AGT GGA TTT TTT ATC TTA TTG CAG CAG CAG AAT 1889Arg Ala Ser Cys Val Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn505 510 515TCT TGT AAC AGA GTT CCC AAG ATT CTT ATA GAT AAA GTC AAA GAT GAT 1937Ser Cys Asn Arg Val Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp520 525 530 535TCT GAC ATT GTC AAG AAA GAA TTT GCT TCT ATA CTT GGT CAA CTT GTC 1985Ser Asp Ile Val Lys Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val540 545 550TGT ACT CTT CAC GGC ATG TTT TAT CTG ACA AGT TCT TTA ACA GAA CCT 2033Cys Thr Leu His Gly Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro555 560 565TTC TCT GAA CAC GGA CAT GTG GAC CTC TTC TGT AGG AAC TTG AAA GCC 2081Phe Ser Glu His Gly His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala570 575 580ACT TCT CAA CAT GAA TGT TCA TCT TCT CAA CTA AAA GCT TCT GTC TGC 2129Thr Ser Gln His Glu Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys585 590 595AAG CCA TTC CTT TTC CTA CTG AAA AAA AAA ATA CCT AGT CCA GTA AAA 2177Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys600 605 610 615CTT GCT TTC ATA GAT AAT CTA CAT CAT CTT TGT AAG CAT CTT GAT TTT 2225Leu Ala Phe Ile Asp Asn Leu His His Leu Cys Lys His Leu Asp Phe620 625 630AGA GAA GAT GAA ACA GAT GTA AAA GCA GTT CTT GGA ACT TTA TTA AAT 2273Arg Glu Asp Glu Thr Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn635 640 645TTA ATG GAA GAT CCA GAC AAA GAT GTT AGA GTG GCT TTT AGT GGA AAT 2321Leu Met Glu Asp Pro Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn650 655 660ATC AAG CAC ATA TTG GAA TCC TTG GAC TCT GAA GAT GGA TTT ATA AAG 2369Ile Lys His Ile Leu Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys665 670 675GAG CTT TTT GTC TTA AGA ATG AAG GAA GCA TAT ACA CAT GCC CAA ATA 2417Glu Leu Phe Val Leu Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile680 685 690 695TCA AGA AAT AAT GAG CTG AAG GAT ACC TTG ATT CTT ACA ACA GGG GAT 2465Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp700 705 710ATT GGA AGG GCC GCA AAA GGA GAT TTG GTA CCA TTT GCA CTC TTA CAC 2513Ile Gly Arg Ala Ala Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His715 720 725TTA TTG CAT TGT TTG TTA TCC AAG TCA GCA TCT GTC TCT GGA GCA GCA 2561Leu Leu His Cys Leu Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala730 735 740TAC ACA GAA ATT AGA GCT CTG GTT GCA GCT AAA AGT GTT AAA CTG CAA 2609Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln745 750 755AGT TTT TTC AGC CAG TAT AAG AAA CCC ATC TGT CAG TTT TTG GTA GAA 2657Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu760 765 770 775TCC CTT CAC TCT AGT CAG ATG ACA GCA CTT CCG AAT ACT CCA TGC CAG 2705Ser Leu His Ser Ser Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln780 785 790AAT GCT GAC GTG CGA AAA CAA GAT GTG GCT CAC CAG AGA GAA ATG GCT 2753Asn Ala Asp Val Arg Lys Gln Asp Val Ala His Gln Arg Glu Met Ala795 800 805TTA AAT ACG TTG TCT GAA ATT GCC AAC GTT TTC GAC TTT CCT GAT CTT 2801Leu Asn Thr Leu Ser Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu810 815 820AAT CGT TTT CTT ACT AGG ACA TTA CAA GTT CTA CTA CCT GAT CTT GCT 2849Asn Arg Phe Leu Thr Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala825 830 835GCC AAA GCA AGC CCT GCA GCT TCT GCT CTC ATT CGA ACT TTA GGA AAA 2897Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys840 845 850 855CAA TTA AAT GTC AAT CGT AGA GAG ATT TTA ATA AAC AAC TTC AAA TAT 2945Gln Leu Asn Val Asn Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr860 865 870ATT TTT TCT CAT TTG GTC TGT TCT TGT TCC AAA GAT GAA TTA GAA CGT 2993Ile Phe Ser His Leu Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg875 880 885GCC CTT CAT TAT CTG AAG AAT GAA ACA GAA ATT GAA CTG GGG AGC CTG 3041Ala Leu His Tyr Leu Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu890 895 900TTG AGA CAA GAT TTC CAA GGA TTG CAT AAT GAA TTA TTG CTG CGT ATT 3089Leu Arg Gln Asp Phe Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile905 910 915GGA GAA CAC TAT CAA CAG GTT TTT AAT GGT TTG TCA ATA CTT GCC TCA 3237Gly Glu His Tyr Gln Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser920 925 930 935TTT GCA TCC AGT GAT GAT CCA TAT CAG GGC CCG AGA GAT ATC ATA TCA 3185Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser940 945 950CCT GAA CTG ATG GCT GAT TAT TTA CAA CCC AAA TTG TTG GGC ATT TTG 3233Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu955 960 965GCT TTT TTT AAC ATG CAG TTA CTG AGC TCT AGT GTT GGC ATT GAA GAT 3281Ala Phe Phe Asn Met Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp970 975 980AAG AAA ATG GCC TTG AAC AGT TTG ATG TCT TTG ATG AAG TTA ATG GGA 3329Lys Lys Met Ala Leu Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly985 990 995CCC AAA CAT GTC AGT TCT GTG AGG GTG AAG ATG ATG ACC ACA CTG AGA 3377Pro Lys His Val Ser Ser Val Arg Val Lys Met Met Thr Thr Leu Arg01015ACT GGC CTT CGA TTC AAG GAT GAT TTT CCT GAA TTG TGT TGC AGA GCT 3425Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala0TGG GAC TGC TTT GTT CGC TGC CTG GAT CAT GCT TGT CTG GGC TCC CTT 3473Trp Asp Cys Phe Val Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu5CTC AGT CAT GTA ATA GTA GCT TTG TTA CCT CTT ATA CAC ATC CAG CCT 3521Leu Ser His Val Ile Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro0AAA GAA ACT GCA GCT ATC TTC CAC TAC CTC ATA ATT GAA AAC AGG GAT 3569Lys Glu Thr Ala Ala Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp5GCT GTG CAA GAT TTT CTT CAT GAA ATA TAT TTT TTA CCT GAT CAT CCA 3617Ala Val Gln Asp Phe Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro01095GAA TTA AAA AAG ATA AAA GCC GTT CTC CAG GAA TAC AGA AAG GAG ACC 3665Glu Leu Lys Lys Ile Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr0TCT GAG AGC ACT GAT CTT CAG ACA ACT CTT CAG CTC TCT ATG AAG GCC 3713Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala5ATT CAA CAT GAA AAT GTC GAT GTT CGT ATT CAT GCT CTT ACA AGC TTG 3761Ile Gln His Glu Asn Val Asp Val Arg Ile His Ala Leu Thr Ser Leu0AAG GAA ACC TTG TAT AAA AAT CAG GAA AAA CTG ATA AAG TAT GCA ACA 3809Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr5GAC AGT GAA ACA GTA GAA CCT ATT ATC TCA CAG TTG GTG ACA GTG CTT 3857Asp Ser Glu Thr Val Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu01175TTG AAA GGT TGC CAA GAT GCA AAC TCT CAA GCT CGG TTG CTC TGT GGG 3905Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly0GAA TGT TTA GGG GAA TTG GGG GCG ATA GAT CCA GGT CGA TTA GAT TTC 3953Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe5TCA ACA ACT GAA ACT CAA GGA AAA GAT TTT ACA TTT GTG ACT GGA GTA 4001Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val0GAA GAT TCA AGC TTT GCC TAT GGA TTA TTG ATG GAG CTA ACA AGA GCT 4049Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala5TAC CTT GCG TAT GCT GAT AAT AGC CGA GCT CAA GAT TCA GCT GCC TAT 4097Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala Gln Asp Ser Ala Ala Tyr01255GCC ATT CAG GAG TTG CTT TCT ATT TAT GAC TGT AGA GAG ATG GAG ACC 4145Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr0AAC GGC CTA GGT CAC CAA TTG TGG AGG AGA TTT CCT GAG CAT GTT CGG 4193Asn Glu Pro Gly His Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg5GAA ATA CTA GAA CCT CAT CTA AAT ACC AGA TAC AAG AGT TCT CAG AAG 4241Glu Ile Leu Glu Pro His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys0TCA ACC GAT TGG TCT GGA GTA AAG AAG CCA ATT TAC TTA AGT AAA TTG 4289Ser Thr Asp Trp Ser Gly Val Lys Lys Pro Ile Tyr Leu Sar Lys Leu5GGT AGT AAC TTT GCA GAA TGG TCA GCA TCT TGG GCA GGT TAT CTT ATT 4337Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile01335ACA AAG GTT CGA CAT GAT CTT GCC AGT AAA ATT TTC ACC TGC TGT AGC 4385Thr Lys Val Arg His Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser0ATT ATG ATG AAG CAT GAT TTC AAA GTG ACC ATC TAT CTT CTT CCA CAT 4433Ile Met Met Lys His Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His5ATT CTG GTG TAT GTC TTA CTG GGT TGT AAT CAA GAA GAT CAG CAG GAG 4481Ile Leu Val Tyr Val Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu0GTT TAT GCA GAA ATT ATG GCA GTT CTA AAG CAT GAC GAT CAG CAT ACC 4529Val Tyr Ala Glu Ile Met Ala Val Leu Lys His Asp Asp Gln His Thr5ATA AAT ACC CAA GAC ATT GCA TCT GAT CTG TGT CAA CTC AGT ACA CAG 4577Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln01415ACT GTG TTC TCC ATG CTT GAC CAT CTC ACA CAG TGG GCA AGG CAC AAA 4625Thr Val Phe Ser Met Leu Asp His Leu Thr Gln Trp Ala Arg His Lys0TTT CAG GCA CTG AAA GCT GAG AAA TGT CCA CAC AGC AAA TCA AAC AGA 4673Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg5AAT AAG GTA GAC TCA ATG GTA TCT ACT GTG GAT TAT GAA GAC TAT CAG 4721Asn Lys Val Asp Ser Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln0AGT GTA ACC CGT TTT CTA GAC CTC ATA CCC CAG GAT ACT CTG GCA GTA 4769Ser Val Thr Arg Phe Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val5GCT TCC TTT CGC TCC AAA GCA TAC ACA CGA GCT GTA ATG CAC TTT GAA 4817Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu01495TCA TTT ATT ACA GAA AAG AAG CAA AAT ATT CAG GAA CAT CTT GGA TTT 4865Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe0TTA CAG AAA TTG TAT GCT GCT ATG CAT GAA CCT GAT GGA GTG GCC GGA 4913Leu Gln Lys Leu Tyr Ala Ala Met His Glu Pro Asp Gly Val Ala Gly5GTC AGT GCA ATT AGA AAG GCA GAA CCA TCT CTA AAA GAA CAG ATC CTT 4961Val Ser Ala Ile Arg Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu0GAA CAT GAA AGC CTT GGC TTG CTG AGG GAT GCC ACT GCT TGT TAT GAC 5009Glu His Glu Ser Leu Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp5AGG GCT ATT CAG CTA GAA CCA GAC CAG ATC ATT CAT TAC CAT GGT GTA 5057Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile Ile His Tyr His Gly Val01575GTA AAG TCC ATG TTA GGT CTT GGT CAG CTG TCT ACT GTT ATC ACT CAG 5105Val Lys Ser Met Leu Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln0GTG AAT GGA GTG CAT GCT AAC AGG TCC GAG TGG ACA GAT GAA TTA AAC 5153Val Asn Gly Val His Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn5ACG TAC AGA GTG GAA GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG 5201Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val0GAA AAC TAT TTG GCA GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA 5245Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg5CTG GGA CAG CTA TTA TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT 5297Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe01655TAT GAC TCA CTG AAA CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA 5345Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser0GCT GCA AGC TTT GAA AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT 5393Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile5GTG AGA TTG CAC ATG TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT 5441Val Arg Leu His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu0TTC CAG CAT TCT CCA GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG 5485Phe Gln His Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp5GTA GCT CGA CTA GAA ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT 5537Val Ala Arg Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro01735ATC CTG GCT CTC CGG AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT 5585Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp0TAC AAT GAA ATG GTT GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT 5633Tyr Asn Glu Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala5AGA AAG GCT GGT CAC CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA 5681Arg Lys Ala Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala0GGG GAA TCA CGA CTC GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC 5729Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu5TGG TCC AAG GGT GAT GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT 5777Trp Ser Lys Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly01815GTT GAA TTA TGT TTT CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC 5825Val Glu Leu Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn0ATG TTA ATC CAT GGT CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA 5573Met Leu Ile His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu5GAA ACA GCT AAC TTT GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT 5921Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp0GTG ACC GCG TGC CTG CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC 5969Val Thr Ala Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala5AAG TAC TAT GAC AAA TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA 6017Lys Tyr Tyr Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu01895AAG CAA GGT GAT CTC ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT 6065Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser0CTA CAA TAT GGA AAT CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA 6113Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu5ACT CTA TGG CTT GAT TAT GGT ACA AAG GCA TAT GAA TGG GAA AAA GCT 6161Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala0GGC CGC TCC GAT CGT GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC 6209Gly Arg Ser Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn5AAG GTT ATC ACA GAG CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG 6257Lys Val Ile Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu01975ACT GCT TTT TCA CAA TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA 6305Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu0GTT TTT GTT GTG CTT GAT GGA AAT AAT AGC CAA GTA TTT CTA GCC TAT 6353Val Phe Val Val Leu Asp Gly Asn Asn Ser Gln Val Phe Leu Ala Tyr5CCT CAA CAA GCA ATG TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT 6401Pro Gln Gln Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr201020152020CCC ATG CGT GTG AAC AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT 6449Pro Met Arg Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His202520302035ATG AAA AAA TCC TTA GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA 6497Met Lys Lys Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr2040204520502055GAT AAG CTT CTA GAA TTG TGC AAT AAA CCG GTG GAA ATT CTT GCT TCT 6545Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro Val Glu Ile Leu Ala Ser206020652070CTT CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC 6593Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe207520802085TAC ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA 6641Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg209020952100CTA ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA 6689Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala2GAG TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA 6737Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro22135CTA AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT 6785Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala G1y2TTG AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG 6833Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met2ACA GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA 6881Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu2TCT GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT 6929Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro2CCT ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA 6977Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser2200220522102215TGG TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA 7025Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser222022252230ATG GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT 7073Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile223522402245CTC TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT 7121Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys225022552260CTT TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT 7163Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe226522702275CGC CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG 7217Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu2280228522902295GGT CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT 7265Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp230023052310CAG CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT 7313Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro231523202325CTT GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG 7361Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu233023352340AAT GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT 7409Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu234523502355GAC ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG 7457Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val2360236523702375ACA GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA 7505Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln238023852390GAA GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT 7553Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr239524002405CCA TAT ATG TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA 7602Pro Tyr Met2410AGTAAAAAAA AAAAAAAAAA AA 7624(2)SEQ ID NO24的說明(i)序列特征(A)長度2410個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型蛋白(xi)序列描述SEQ ID NO24Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe0Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp51040His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu5Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr0Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile5Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu0Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr51120Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg5Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu0Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile5Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser0Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile51200Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp5Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu0Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg5Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr0Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg51280Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr5Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys0Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala5Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser0Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val51360Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys5Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu0Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp5Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu0Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys51440Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr5Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile0Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr5Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn0Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His51520Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro5Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg0Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln5Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln0Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser51600Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys5Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys0Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys5Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala0Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr51680Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu5Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser0Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn5Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu0Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp51760Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala5Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr0Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala5Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu0Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu51840Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala5Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu0Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met5Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile0Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr51920Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys5Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg0Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr5Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg0Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn52000Ser Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060Pro Val Glu Ile Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu2065207020752080Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp208520902095Asp Leu Arg Lys Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn2Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile2Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu2Trp Val Asn Asn Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr22160Lys Glu Lys Gly Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met2Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu2Phe Leu Leu Pro Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg2Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys221022152220Arg Ser Thr Ala Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly2225223022352240Asp Arg His Gly Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys224522502255Val His Val Asp Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu226022652270Val Pro Glu Ile Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly227522802285Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val229022952300Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu2305231023152320Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys232523302335Gly His Ser Lys Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu234023452350Lys Ala Lys Thr His Val Leu Asp Ile Glu Gln Arg Leu Gln Gly Val235523602365Ile Lys Thr Arg Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly237023752380His Val His Tyr Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys2385239023952400Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met24052410(2)SEQ ID NO25的說明(i)序列特征(A)長度7502個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型cDNA(ix)特征(A)姓名/符號CDS(B)位置1..7440(xi)序列描述SEQ ID NO25ATG GGT CAT GCT GTG GAA TGG CCA GTG GTC ATG AGC CGA TTT TTA AGT 45Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15CAA TTA GAT GAA CAC ATG GGA TAT TTA CAA TCA GCT CCT TTG CAG TTG 95Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30ATG AGT ATG CAA AAT TTA GAA TTT ATT GAA GTC ACT TTA TTA ATG GTT 144Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45CTT ACT CGT ATT ATT GCA ATT GTG TTT TTT AGA AGG CAA GAA CTC TTA 152Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60CTT TGG CAG ATA GGT TGT GTT CTG CTA GAG TAT GGT AGT CCA AAA ATT 240Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80AAA TCC CTA GCA ATT AGC TTT TTA ACA GAA CTT TTT CAG CTT GGA GGA 255Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95CTA CCA GCA CAA CCA GCT AGC ACT TTT TTC AGC TCA TTT TTG GAA TTA 336Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110TTA AAA CAC CTT GTA GAA ATG GAT ACT GAC CAA TTG AAA CTC TAT GAA 354Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125GAG CCA TTA TCA AAG CTG ATA AAG ACA CTA TTT CCC TTT GAA GCA GAA 432Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140GCT TAT AGA AAT ATT GAA CCT GTC TAT TTA AAT ATG CTG CTG GAA AAA 480Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160CTC TGT GTC ATG TTT GAA GAC GGT GTG CTC ATG CGG CTT AAG TCT GAT 528Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175TTG CTA AAA GCA GCT TTG TGC CAT TTA CTG CAG TAT TTC CTT AAA TTT 576Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190GTG CCA GCT GGG TAT GAA TCT GCT TTA CAA GTC AGG AAG GTC TAT GTG 624Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205AGA AAT ATT TGT AAA GCT CIT TTG GAT GTG CTT GGA ATT GAG GTA GAT 672Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220GCA GAG TAC TTG TTG GGC CCA CTT TAT GCA GCT TTG AAA ATG GAA AGT 720Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240ATG GAA ATC ATT GAG GAG ATT CAA TGC CAA ACT CAA CAG GAA AAC CTC 768Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255AGC AGT AAT AGT GAT GGA ATA TCA CCC AAA AGG CGT CGT CTC AGC TCG 816Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270TCT CTA AAC CCT TCT AAA AGA GCA CCA AAA CAG ACT GAG GAA ATT AAA 864Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285CAT GTG GAC ATG AAC CAA AAG AGC ATA TTA TGG AGT GCA CTG AAA CAG 912His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300AAA GCT GAA TCC CTT CAG ATT TCC CTT GAA TAC AGT GGC CTA AAG AAT 960Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320CCT GTT ATT GAG ATG TTA GAA GGA ATT GCT GTT GTC TTA CAA CTG ACT 1008Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335GCT CTG TGT ACT GTT CAT TGT TCT CAT CAA AAC ATG AAC TGC CGT ACT 1056Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350TTC AAG GAC TGT CAA CAT AAA TCC AAG AAG AAA CCT TCT GTA GTG ATA 1104Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365ACT TGG ATG TCA TTG GAT TTT TAC ACA AAA GTG CTT AAG AGC TGT AGA 1152Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380AGT TTG TTA GAA TCT GTT CAG AAA CTG GAC CTG GAG GCA ACC ATT GAT 1200Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400AAG GTG GTG AAA ATT TAT GAT GCT TTG ATT TAT ATG CAA GTA AAC AGT 1248Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415TCA TTT GAA GAT CAT ATC CTG GAA GAT TTA TGT GGA ATG CTC TCA CTT 1296Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430CCA TGG ATT TAT TCC CAT TCT GAT GAT GGC TGT TTA AAG TTG ACC ACA 1344Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445TTT GCC GCT AAT CTT CTA ACA TTA AGC TGT AGG ATT TCA GAT AGC TAT 1392Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460TCA CCA CAG GCA CAA TCA CGA TGT GTG TTT CTT CTG ACT CTG TTT CCA 1440Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480AGA AGA ATA TTC CTT GAG TGG AGA ACA GCA GTT TAC AAC TGG GCC CTG 1486Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495CAG AGC TCC CAT GAA GTA ATC CGG GCT AGT TGT GTT AGT GGA TTT TTT 1536Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510ATC TTA TTG CAG CAG CAG AAT TCT TGT AAC AGA GTT CCC AAG ATT CTT 1584Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525ATA GAT AAA GTC AAA GAT GAT TCT GAC ATT GTC AAG AAA GAA TTT GCT 1632Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540TCT ATA CTT GGT CAA CTT GTC TGT ACT CTT CAC GGC ATG TTT TAT CTG 1680Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560ACA AGT TCT TTA ACA GAA CCT TTC TCT GAA CAC GGA CAT GTG GAC CTC 1728Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575TTC TGT AGG AAC TTG AAA GCC ACT TCT CAA CAT GAA TGT TCA TCT TCT 1776Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590CAA CTA AAA GCT TCT GTC TGC AAG CCA TTC CTT TTC CTA CTG AAA AAA 1824Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605AAA ATA CCT AGT CCA GTA AAA CTT GCT TTC ATA GAT AAT CTA CAT CAT 1872Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620CTT TGT AAG CAT CTT GAT TTT AGA GAA GAT GAA ACA GAT GTA AAA GCA 1920Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640GTT CTT GGA ACT TTA TTA AAT TTA ATG GAA GAT CCA GAC AAA GAT GTT 1968Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655AGA GTG GCT TTT AGT GGA AAT ATC AAG CAC ATA TTG GAA TCC TTG GAC 2016Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670TCT GAA GAT GGA TTT ATA AAG GAG CTT TTT GTC TTA AGA ATG AAG GAA 2064Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685GCA TAT ACA CAT GCC CAA ATA TCA AGA AAT AAT GAG CTG AAG GAT ACC 2112Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700TTG ATT CTT ACA ACA GGG GAT ATT GGA AGG GCC GCA AAA GGA GAT TTG 2160Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720GTA CCA TTT GCA CTC TTA CAC TTA TTG CAT TGT TTG TTA TCC AAG TCA 2208Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735GCA TCT GTC TCT GGA GCA GCA TAC ACA GAA ATT AGA GCT CTG GTT GCA 2256Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750GCT AAA AGT GTT AAA CTG CAA AGT TTT TTC AGC CAG TAT AAG AAA CCC 2304Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765ATC TGT CAG TTT TTG GTA GAA TCC CTT CAC TCT AGT CAG ATG ACA GCA 2352Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780CTT CCG AAT ACT CCA TGC CAG AAT GCT GAC GTG CGA AAA CAA GAT GTG 2400Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800GCT CAC CAG AGA GAA ATG GCT TTA AAT ACG TTG TCT GAA ATT GCC AAC 2448Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815GTT TTC GAC TTT CCT GAT CTT AAT CGT TTT CTT ACT AGG ACA TTA CAA 2496Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830GTT CTA CTA CCT GAT CTT GCT GCC AAA GCA AGC CCT GCA GCT TCT GCT 2544Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845CTC ATT CGA ACT TTA GGA AAA CAA TTA AAT GTC AAT CGT AGA GAG ATT 2592Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860TTA ATA AAC AAC TTC AAA TAT ATT TTT TCT CAT TTG GTC TGT TCT TGT 2640Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880TCC AAA GAT GAA TTA GAA CGT GCC CTT CAT TAT CTG AAG AAT GAA ACA 2688Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895GAA ATT GAA CTG GGG AGC CTG TTG AGA CAA GAT TTC CAA GGA TTG CAT 2736Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910AAT GAA TTA TTG CTG CGT ATT GGA GAA CAC TAT CAA CAG GTT TTT AAT 2784Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925GGT TTG TCA ATA CTT GCC TCA TTT GCA TCC AGT GAT GAT CCA TAT CAG 2832Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940GGC CCG AGA GAT ATC ATA TCA CCT GAA CTG ATG GCT GAT TAT TTA CAA 2880Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960CCC AAA TTG TTG GGC ATT TTG GCT TTT TTT AAC ATG CAG TTA CTG AGC 2928Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975TCT AGT GTT GGC ATT GAA GAT AAG AAA ATG GCC TTG AAC AGT TTG ATG 2976Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990TCT TTG ATG AAG TTA ATG GGA CCC AAA CAT GTC AGT TCT GTG AGG GTG 3024Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005AAG ATG ATG ACC ACA CTG AGA ACT GGC CTT CGA TTC AAG GAT GAT TTT 3072Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe0CCT GAA TTG TGT TGC AGA GCT TGG GAC TGC TTT GTT CGC TGC CTG GAT 3120Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp51040CAT GCT TGT CTG GGC TCC CTT CTC AGT CAT GTA ATA GTA GCT TTG TTA 3168His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu5CCT CTT ATA CAC ATC CAG CCT AAA GAA ACT GCA GCT ATC TTC CAC TAC 3216Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr0CTC ATA ATT GAA AAC AGG GAT GCT GTG CAA GAT TTT CTT CAT GAA ATA 3264Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile5TAT TTT TTA CCT GAT CAT CCA GAA TTA AAA AAG ATA AAA GCC GTT CTC 3312Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu0CAG GAA TAC AGA AAG GAG ACC TCT GAG AGC ACT GAT CTT CAG ACA ACT 3360Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr51120CTT CAG CTC TCT ATG AAG GCC ATT CAA CAT GAA AAT GTC GAT GTT CGT 3408Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg5ATT CAT GCT CTT ACA AGC TTG AAG GAA ACC TTG TAT AAA AAT CAG GAA 3456Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu0AAA CTG ATA AAG TAT GCA ACA GAC AGT GAA ACA GTA GAA CCT ATT ATC 3504Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile5TCA CAG TTG GTG ACA GTG CTT TTG AAA GGT TGC CAA GAT GCA AAC TCT 3552Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser0CAA GCT CGG TTG CTC TGT GGG GAA TGT TTA GGG GAA TTG GGG GCG ATA 3600Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile51200GAT CCA GGT CGA TTA GAT TTC TCA ACA ACT GAA ACT CAA GGA AAA GAT 3648Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp5TTT ACA TTT GTG ACT GGA GTA GAA GAT TCA AGC TTT GCC TAT GGA TTA 3696Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu0TTG ATG GAG CTA ACA AGA GCT TAC CTT GCG TAT GCT GAT AAT AGC CGA 3744Leu Met Glu Leu Thr Arg Ala Tyr Leu AAa Tyr Ala Asp Asn Ser Arg5GCT CAA GAT TCA GCT GCC TAT GCC ATT CAG GAG TTG CTT TCT ATT TAT 3792Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr0GAC TGT AGA GAG ATG GAG ACC AAC GGC CCA GGT CAC CAA TTG TGG AGG 3840Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg51280AGA TTT CCT GAG CAT GTT CGG GAA ATA CTA GAA CCT CAT CTA AAT ACC 3888Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr5AGA TAC AAG AGT TCT CAG AAG TCA ACC GAT TGG TCT GGA GTA AAG AAG 3936Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys0CCA ATT TAC TTA AGT AAA TTG GGT AGT AAC TTT GCA GAA TGG TCA GCA 3984Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala5TCT TGG GCA GGT TAT CTT ATT ACA AAG GTT CGA CAT GAT CTT GCC AGT 4032Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser0AAA ATT TTC ACC TGC TGT AGC ATT ATG ATG AAG CAT GAT TTC AAA GTG 4080Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val51360ACC ATC TAT CTT CTT CCA CAT ATT CTG GTG TAT GTC TTA CTG GGT TGT 4128Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys5AAT CAA GAA GAT CAG CAG GAG GTT TAT GCA GAA ATT ATG GCA GTT CTA 4176Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu0AAG CAT GAC GAT CAG CAT ACC ATA AAT ACC CAA GAC ATT GCA TCT GAT 4224Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp5CTG TGT CAA CTC AGT ACA CAG ACT GTG TTC TCC ATG CTT GAC CAT CTC 4272Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu0ACA CAG TGG GCA AGG CAC AAA TTT CAG GCA CTG AAA GCT GAG AAA TGT 4320Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys51440CCA CAC AGC AAA TCA AAC AGA AAT AAG GTA GAC TCA ATG GTA TCT ACT 4368Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr5GTG GAT TAT GAA GAC TAT CAG AGT GTA ACC CGT TTT CTA GAC CTC ATA 4416Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile0CCC CAG GAT ACT CTG GCA GTA GCT TCC TTT CGC TCC AAA GCA TAC ACA 4464Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr5CGA GCT GTA ATG CAC TTT GAA TCA TTT ATT ACA GAA AAG AAG CAA AAT 4512Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn0ATT CAG GAA CAT CTT GGA TTT TTA CAG AAA TTG TAT GCT GCT ATG CAT 4560Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His51520GAA CCT GAT GGA GTG GCC GGA GTC AGT GCA ATT AGA AAG GCA GAA CCA 4608Glu Pro Asp Gly Val Ala Gly Val ser Ala Ile Arg Lys Ala Glu Pro5TCT CTA AAA GAA CAG ATC CTT GAA CAT GAA AGC CTT GGC TTG CTG AGG 4656Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg0GAT GCC ACT GCT TGT TAT GAC AGG GCT ATT CAG CTA GAA CCA GAC CAG 4704Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln5ATC ATT CAT TAC CAT GGT GTA GTA AAG TCC ATG TTA GGT CTT GGT CAG 4752Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln0CTG TCT ACT GTT ATC ACT CAG GTG AAT GGA GTG CAT GCT AAC AGG TCC 4800Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser51600GAG TGG ACA GAT GAA TTA AAC ACG TAC AGA GTG GAA GCA GCT TGG AAA 4848Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys5TTG TCA CAG TGG GAT TTG GTG GAA AAC TAT TTG GCA GCA GAT GGA AAA 4896Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys0TCT ACA ACA TGG AGT GTC AGA CTG GGA CAG CTA TTA TTA TCA GCC AAA 4944Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys5AAA AGA GAT ATC ACA GCT TTT TAT GAC TCA CTG AAA CTA GTG AGA GCA 4992Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala0GAA CAA ATT GTA CCT CTT TCA GeT GCA AGC TTT GAA AGA GGC TCC TAC 5040Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr51680CAA CGA GGA TAT GAA TAT ATT GTG AGA TTG CAC ATG TTA TGT GAG TTG 5088Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu5GAG CAT AGC ATC AAA CCA CTT TTC CAG CAT TCT CCA GGT GAC AGT TCT 5136Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser0CAA GAA GAT TCT CTA AAC TGG GTA GCT CGA CTA GAA ATG ACC CAG AAT 5184Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn5TCC TAC AGA GCC AAG GAG CCT ATC CTG GCT CTC CGG AGG GCT TTA CTA 5232Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu0AGC CTC AAC AAA AGA CCA GAT TAC AAT GAA ATG GTT GGA GAA TGC TGG 5280Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp51760CTG CAG AGT GCC AGG GTA GCT AGA AAG GCT GGT CAC CAC CAG ACA GCC 5328Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala5TAC AAT GCT CTC CTT AAT GCA GGG GAA TCA CGA CTC GCT GAA CTG TAC 5376Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr0GTG GAA AGG GCA AAG TGG CTC TGG TCC AAG GGT GAT GTT CAC CAG GCA 5424Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala5CTA ATI GTT CTT CAA AAA GGT GTT GAA TTA TGT TTT CCT GAA AAT GAA 5472Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu0ACC CCA CCT GAG GGT AAG AAC ATG TTA ATC CAT GGT CGA GCT ATG CTA 5520Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu51840CTA GTG GGC CGA TTT ATG GAA GAA ACA GCT AAC TTT GAA AGC AAT GCA 5568Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala5ATT ATG AAA AAA TAT AAG GAT GTG ACC GCG TGC CTG CCA GAA TGG GAG 5616Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu0GAT GGG CAT TTT TAC CTT GCC AAG TAC TAT GAC AAA TTG ATG CCC ATG 5664Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met5GTC ACA GAC AAC AAA ATG GAA AAG CAA GGT GAT CTC ATC CGG TAT ATA 5712Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile0GTT CTT CAT TTT GGC AGA TCT CTA CAA TAT GGA AAT CAG TTC ATA TAT 5760Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr51920CAG TCA ATG CCA CGA ATG TTA ACT CTA TGG CTT GAT TAT GGT ACA AAG 5808Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys5GCA TAT GAA TGG GAA AAA GCT GGC CGC TCC GAT CGT GTA CAA ATG AGG 5856Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg0AAT GAT TTG GGT AAA ATA AAC AAG GTT ATC ACA GAG CAT ACA AAC TAT 5904Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr5TTA GCT CCA TAT CAA TTT TTG ACT GCT TTT TCA CAA TTG ATC TCT CGA 5952Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg0ATT TGT CAT TCT CAC GAT GAA GTT TTT GTT GTG CTT GAT GGA AAT AAT 6000Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn52000AGC CAA GTA TTT CTA GCC TAT CCT CAA CAA GCA ATG TGG ATG ATG ACA 6048Ser Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015GCT GTG TCA AAG TCA TCT TAT CCC ATG CGT GTG AAC AGA TGC AAG GAA 6096Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030ATC CTC AAT AAA GCT ATT CAT ATG AAA AAA TCC TTA GAG AAG TTT GTT 6144Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045GGA GAT GCA ACT CGC CTA ACA GAT AAG CTT CTA GAA TTG TGC AAT AAA 6192Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060CCG GTT GAT GGA AGT AGT TCC ACA TTA AGC ATG AGC ACT CAT TTT AAA 6240Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys2065207020752080ATG CTT AAA AAG CTG GTA GAA GAA GCA ACA TTT AGT GAA ATC CTC ATT 6288Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile208520902095CCT CTA CAA TCA GTC ATG ATA CCT ACA CTT CCA TCA ATT CTG GGT ACC 6336Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr2CAT GCT AAC CAT GCT AGC CAT GAA CCA TTT CCT GGA CAT TGG GCC TAT 6384His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr2ATT GCA GGG TTT GAT GAT ATG GTG GAA ATT CTT GCT TCT CTT CAG AAA 6432Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys2CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC TAC ATC ATG 6480Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met22l60ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA CTA ATG GAA 6528Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu2TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA GAG TCT CGT 6576Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg2AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA CTA AAT GAT 6624Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp2GAA TCT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT TTG AGA CCT 6672Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro221022152220ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG ACA GGA AAA 6720Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys2225223022352240GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA TCT GAA AAA 6768Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys224522502255CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT CCT ATT TTT 6816Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe226022652270CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA TGG TAC AGT 6864His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser227522802285AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA ATG GTT GGT 6912Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly229022952300TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT CTC TTT GAT 6960Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp2305231023152320TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT CTT TTC AAT 7008Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn232523302335AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT CGC CTG ACT 7056Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr234023452350CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG GGT CTT TTT 7104His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe235523602365CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT CAG CGA GAG 7152Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu237023752380CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT CTT GTG GAA 7200Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu2385239023952400TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG AAT GAA ACT 7248Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr240524102415GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT GAC ATT GAG 7296Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu242024252430CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG ACA GGA CTG 7344Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu243524402445CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA GAA GCT ACT 7392Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr245024552460GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT CCA TAT ATG 7440Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met2465247024752480TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA AGTAAAAAAA AAAAAAAAAA7500AA 7502(2)SEQ ID NO26的說明(i)序列特征(A)長度2480個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型蛋白(xi)序列描述SEQ ID NO26Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe0Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp51040His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu5Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr0Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile5Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu0Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr51120Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg5Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu0Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile5Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser0Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile51200Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp5Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu0Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg5Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr0Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg51280Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr5Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys0Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala5Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser0Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val51360Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys5Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu0Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp5Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu14101415 1420Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys51440Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr5Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile0Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr5Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn0Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His51520Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro5Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg0Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln5Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln0Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser51600Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys5Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys0Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys5Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala0Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr51680Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu5Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser0Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn5Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu0Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp51760Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala5Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr0Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala5Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu0Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu51840Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala5Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu0Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met5Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile0Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr51920Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys5Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg0Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr5Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg0Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn52000Ser Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys2065207020752080Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile208520902095Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr2His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr2Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys2Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met22160Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu2Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg2Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp2Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro221022152220Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys2225223022352240Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys224522502255Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe226022652270His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser227522802285Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly229022952300Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp2305231023152320Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn232523302335Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr234023452350His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe235523602365Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu237023752380Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu2385239023952400Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr240524102415Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu242024252430Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu243524402445Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr245024552460Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met2465247024752480(2)SEQ ID NO27的說明(i)序列特征(A)長度878個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型DNA(xi)序列描述SEQ ID NO27ATCCATTGTG TTGGAAAGGA ATGATGAATG TGGGATTATT GAATGGGTGA ACAATACTGC 60TGGCTTGAGA CCTATTCTGA CCAAAATATA TAAAGAAAAG GGAGTGTATA TGACAGGAAA 120GGAGCTTCGC CAGTGTATGC TACCAAAGTC AGCAGCTTTA TCTGAAAAAC TCAAAGTATT 180CCAAGAATTA CTCCTGCCCA GGCATCCTCC TGTTTTTCAT GAGTGGTTTC TGAGAACATT 240CCCTGATCCT ACATCATGGT ACAGTAGCAG ATCTGCATAT TGCCGCTCTA CTGCAGTCAT 300GTCAATGGTT GGCTACATCC TGGGGCTTGG AGACCGTCAT GGTGAAAACA TTCTTTTTGA 360CTCTTTCACT GGTGAATGTG TACATGTAGA TTTCAACTGT CTTTTTAATA AGGGAGAAAC 420GTTTGAAGTT CCGGAAATTG TACCATTTCG ACTGACTCAT AATATGGTTA ATGGAATGGG 480TCCTATGGGA ACAGAGGGTC TATTTCGAAG AGCATGTGAA GTTACACTGA GACTGATGAG 540GGATCAGAGA GAACCTTTAA TGAGTGTCTT AAAGACTTTT CTACACGATC CTCTAGTGGA 600GTGGAGTAAA CCAGTGAAAG GACACTCCAA AGCACCACTG AATGAAACCG GGGAAGTTGT 660CAATGAGAAG GCCAAGACCC ATGTTCTTGA CATTGAACAA CGACTACAAG GTGTGATCAA 720AACCCGAAAT AGAGTAACAG GGCTGCCATT ATCTATTGAA GGACATGTGC ATTACCTCAT 780ACAAGAAGCT ACTGATGAAA ACTTACTCTG TCAGATGTAC CTTGGTTGGA CCCCATATAT 840GTAAAATAAA ATTATTTCAA AGAAAAAAAA AAAAAAAA 878(2)SEQ ID NO28的說明(i)序列特征(A)長度7935個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型cDNA(ix)特征(A)姓名/符號CDS(B)位置1..7932(xi)序列描述SEQ ID NO28ATG GGG GAA CAT GGC CTG GAG CTG GCT TCC ATG ATC CCC GCC CTG CGG 48Met Gly Glu His Gly Leu Glu Leu Ala Ser Met Ile Pro Ala Leu Arg1 5 10 15GAG CTG GGC AGT GCC ACA CCA GAG GAA TAT AAT ACA GTT GTA GAG AAG 96Glu Leu Gly Ser Ala Thr Pro Glu Glu Tyr Asn Thr Val Val Gln Lys20 25 30CCA AGA CAA ATT CTG TGT CAA TTC ATT GAC CGG ATA CTT ACA GAT GTA 144Pro Arg Gln Ile Leu Cys Gln Phe Ile Asp Arg Ile Leu Thr Asp Val35 40 45AAT GTT GTT GCT GTA GAA CTT GTA AAG AAA ACT GAC TCT CAG CCA ACC 192Asn Val Val Ala Val Glu Leu Val Lys Lys Thr Asp Ser Gln Pro Thr50 55 60TCC GTG ATG TTG CTT GAT TTC ATC CAG CAT ATC ATG AAA TCC TCC CCA 240Ser Val Met Leu Leu Asp Phe Ile Gln His Ile Met Lys Ser Ser Pro65 70 75 80CTT ATG TTT GTA AAT GTG AGT GGA AGC CAT GAG CGC AAA GGC AGT TGT 288Leu Met Phe Val Asn Val Ser Gly Ser His Glu Arg Lys Gly Ser Cys85 90 95ATT GAA TTC AGT AAT TGG ATC ATA ACG AGA CTT CTG CGG ATT GCA GCA 336Ile Glu Phe Ser Asn Trp Ile Ile Thr Arg Leu Leu Arg Ile Ala Ala100 105 110ACT CCC TCC TGT CAT TTG TTA CAC AAG AAA ATC TGT GAA GTC ATC TGT 384Thr Pro Ser Cys His Leu Leu His Lys Lys Ile Cys Glu Val Ile Cys115 120 125TCA TTA TTA TTT CTT TTT AAA AGC AAG AGT CCT GCT ATT TTT GGG GTA 432Ser Leu Leu Phe Leu Phe Lys Ser Lys Ser Pro Ala Ile Phe Gly Val130 135 140CTC ACA AAA GAA TTA TTA CAA CTT TTT GAA GAC TTG GTT TAC CTC CAT 480Leu Thr Lys Glu Leu Leu Gln Leu Phe Glu Asp Leu Val Tyr Leu His145 150 155 160AGA AGA AAT GTG ATG GGT CAT GCT GTG GAA TGG CCA GTG GTC ATG AGC 528Arg Arg Asn Val Met Gly His Ala Val Glu Trp Pro Val Val Met Ser165 170 175CGA TTT TTA AGT CAA TTA GAT GAA CAC ATG GGA TAT TTA CAA TCA GCT 576Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala180 185 190CCT TTG CAG TTG ATG AGT ATG CAA AAT TTA GAA TTT ATT GAA GTC ACT 624Pro Leu Gln Leu Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr195 200 205TTA TTA ATG GTT CTT ACT CGT ATT ATT GCA A7T GTG TTT TTT AGA AGG 672Leu Leu Met Val Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg210 215 220CAA GAA CTC TTA CTT TGG CAG ATA GGT TGT GTT CTG CTA GAG TAT GGT 720Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly225 230 235 240AGT CCA AAA ATT AAA TCC CTA GCA ATT AGC TTT TTA ACA GAA CTT TTT 768Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe245 250 255CAG CTT GGA GGA CTA CCA GCA CAA CCA GCT AGC ACT TTT TTC AGC TCA 816Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser260 265 270TTT TTG GAA TTA TTA AAA CAC CTT GTA GAA ATG GAT ACT GAC CAA TTG 864Phe Leu Glu Leu Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu275 280 285AAA CTC TAT GAA GAG CCA TTA TCA AAG CTG ATA AAG ACA CTA TTT CCC 912Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro290 295 300TTT GAA GCA GAA GCT TAT AGA AAT ATT GAA CCT GTC TAT TTA AAT ATG 960Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met305 310 315 320CTG CTG GAA AAA CTC TGT GTC ATG TTT GAA GAC GGT GTG CTC ATG CGG 1008Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg325 330 335CTT AAG TCT GAT TTG CTA AAA GCA GCT TTG TGC CAT TTA CTG CAG TAT 1056Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr340 345 350TTC CTT AAA TTT GTG CCA GCT GGG TAT GAA TCT GCT TTA CAA GTC AGG 1104Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg355 360 365AAG GTC TAT GTG AGA AAT ATT TGT AAA GCT CTT TTG GAT GTG CTT GGA 1152Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly370 375 380ATT GAG GTA GAT GCA GAG TAC TTG TTG GGC CCA CTT TAT GCA GCT TTG 1200Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu385 390 395 400AAA ATG GAA AGT ATG GAA ATC ATT GAG GAG ATT CAA TGC CAA ACT CAA 1248Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln405 410 415CAG GAA AAC CTC AGC AGT AAT AGT GAT GGA ATA TCA CCC AAA AGG CGT 1296Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg420 425 430CGT CTC AGC TCG TCT CTA AAC CCT TCT AAA AGA GCA CCA AAA CAG ACT 1344Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr435 440 445GAG GAA ATT AAA CAT GTG GAC ATG AAC CAA AAG AGC ATA TTA TGG AGT 1392Glu Glu Ile Lys His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser450 455 460GCA CTG AAA CAG AAA GCT GAA TCC CTT CAG ATT TCC CTT GAA TAC AGT 1440Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser465 470 475 480GGC CTA AAG AAT CCT GTT ATT GAG ATG TTA GAA GGA ATT GCT GTT GTC 1488Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val485 490 495TTA CAA CTG ACT GCT CTG TGT ACT GTT CAT TGT TCT CAT CAA AAC ATG 1536Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met500 505 510AAC TGC CGT ACT TTC AAG GAC TGT CAA CAT AAA TCC AAG AAG AAA CCT 1584Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro515 520 525TCT GTA GTG ATA ACT TGG ATG TCA TTG GAT TTT TAC ACA AAA GTG CTT 1632Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu530 535 540AAG AGC TGT AGA AGT TTG TTA GAA TCT GTT CAG AAA CTG GAC CTG GAG 1680Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu545 550 555 560GCA ACC ATT GAT AAG GTG GTG AAA ATT TAT GAT GCT TTG ATT TAT ATG 1728Ala Thr Ile Asp Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met565 570 575CAA GTA AAC AGT TCA TTT GAA GAT CAT ATC CTG GAA GAT TTA TGT GGT 1776Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly580 585 590ATG CTC TCA CTT CCA TGG ATT TAT TCC CAT TCT GAT GAT GGC TGT TTA 1824Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu595 600 605AAG TTG ACC ACA TTT GCC GCT AAT CTT CTA ACA TTA AGC TGT AGG ATT 1872Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile610 615 620TCA GAT AGC TAT TCA CCA CAG GCA CAA TCA CGA TGT GTG TTT CTT CTG 1920Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu625 630 635 640ACT CTG TTT CCA AGA AGA ATA TTC CTT GAG TGG AGA ACA GCA GTT TAC 1968Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr645 650 655AAC TGG GCC CTG CAG AGC TCC CAT GAA GTA ATC CGG GCT AGT TGT GTT 2016Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val660 665 670AGT GGA TTT TTT ATC TTA TTG CAG CAG CAG AAT TCT TGT AAC AGA GTT 2064Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val675 680 685CCC AAG ATT CTT ATA GAT AAA GTC AAA GAT GAT TCT GAC ATT GTC AAG 2112Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys690 695 700AAA GAA TTT GCT TCT ATA CTT GGT CAA CTT GTC TGT ACT CTT CAC GGC 2160Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly705 710 715 720ATG TTT TAT CTG ACA AGT TCT TTA ACA GAA CCT TTC TCT GAA CAC GGA 2208Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly725 730 735CAT GTG GAC CTC TTC TGT AGG AAC TTG AAA GCC ACT TCT CAA CAT GAA 2256His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu740 745 750TGT TCA TCT TCT CAA CTA AAA GCT TCT GTC TGC AAG CCA TTC CTT TTC 2304Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe755 760 765CTA CTG AAA AAA AAA ATA CCT AGT CCA GTA AAA CTT GCT TTC ATA GAT 2352Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp770 775 780AAT CTA CAT CAT CTT TGT AAG CAT CTT GAT TTT AGA GAA GAT GAA ACA 2400Asn Leu His His Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr785 790 795 800GAT GTA AAA GCA GTT CTT GGA ACT TTA TTA AAT TTA ATG GAA GAT CCA 2448Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro805 810 815GAC AAA GAT GTT AGA GTG GCT TTT AGT GGA AAT ATC AAG CAC ATA TTG 2496Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu820 825 830GAA TCC TTG GAC TCT GAA GAT GGA TTT ATA AAG GAG CTT TTT GTC TTA 2544Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu835 840 845AGA ATG AAG GAA GCA TAT ACA CAT GCC CAA ATA TCA AGA AAT AAT GAG 2592Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu850 855 860CTG AAG GAT ACC TTG ATT CTT ACA ACA GGG GAT ATT GGA AGG GCC GCA 2640Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala865 870 875 880AAA GGA GAT TTG GTA CCA TTT GCA CTC TTA CAC TTA TTG CAT TGT TTG 2688Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu885 890 895TTA TCC AAG TCA GCA TCT GTC TCT GGA GCA GCA TAC ACA GAA ATT AGA 2736Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg900 905 910GCT CTG GTT GCA GCT AAA AGT GTT AAA CTG CAA AGT TTT TTC AGC CAG 2784Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln915 920 925TAT AAG AAA CCC ATC TGT CAG TTT TTG GTA GAA TCC CTT CAC TCT AGT 2832Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser930 935 940CAG ATG ACA GCA CTT CCG AAT ACT CCA TGC CAG AAT GCT GAC GTG CGA 2880Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg945 950 955 960AAA CAA GAT GTG GCT CAC CAG AGA GAA ATG GCT TTA AAT ACG TTG TCT 2928Lys Gln Asp Val Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser965 970 975GAA ATT GCC AAC GTT TTC GAC TTT CCT GAT CTT AAT CGT TTT CTT ACT 2976Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr980 985 990AGG ACA TTA CAA GTT CTA CTA CCT GAT CTT GCT GCC AAA GCA AGC CCT 3024Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro995 10001005GCA GCT TCT GCT CTC ATT CGA ACT TTA GGA AAA CAA TTA AAT GTC AAT 3072Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn0CGT AGA GAG ATT TTA ATA AAC AAC TTC AAA TAT ATT TTT TCT CAT TTG 3120Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu51040GTC TGT TCT TGT TCC AAA GAT GAA TTA GAA CGT GCC CTT CAT TAT CTG 3168Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu5AAG AAT GAA ACA GAA ATT GAA CTG GGG AGC CTG TTG AGA CAA GAT TTC 3216Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe0CAA GGA TTG CAT AAT GAA TTA TTG CTG CGT ATT GGA GAA CAC TAT CAA 3264Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln5CAG GTT TTT AAT GGT TTG TCA ATA CTT GCC TCA TTT GCA TCC AGT GAT 3312Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp0GAT CCA TAT CAG GGC CCG AGA GAT ATC ATA TCA CCT GAA CTG ATG GCT 3360Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala51120GAT TAT TTA CAA CCC AAA TTG TTG GGC ATT TTG GCT TTT TTT AAC ATG 3408Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met5CAG TTA CTG AGC TCT AGT GTT GGC ATT GAA GAT AAG AAA ATG GCC TTG 3456Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu0AAC AGT TTG ATG TCT TTG ATG AAG TTA ATG GGA CCC AAA CAT GTC AGT 3504Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser5TCT GTG AGG GTG AAG ATG ATG ACC ACA CTG AGA ACT GGC CTT CGA TTC 3552Ser Val Arg Val Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe0AAG GAT GAT TTT CCT GAA TTG TGT TGC AGA GCT TGG GAC TGC TTT GTT 3600Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val51200CGC TGC CTG GAT CAT GCT TGT CTG GGC TCC CTT CTC AGT CAT GTA ATA 3648Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile5GTA GCT TTG TTA CCT CTT ATA CAC ATC CAG CCT AAA GAA ACT GCA GCT 3696Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala0ATC TTC CAC TAC CTC ATA ATT GAA AAC AGG GAT GCT GTG CAA GAT TTT 3744Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe5CTT CAT GAA ATA TAT TTT TTA CCT GAT CAT CCA GAA TTA AAA AAG ATA 3792Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile0AAA GCC GTT CTC CAG GAA TAC AGA AAG GAG ACC TCT GAG AGC ACT GAT 3840Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp51280CTT CAG ACA ACT CTT CAG CTC TCT ATG AAG GCC ATT CAA CAT GAA AAT 3888Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn5GTC GAT GTT CGT ATT CAT GCT CTT ACA AGC TTG AAG GAA ACC TTG TAT 3936Val Asp Val Arg Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr0AAA AAT CAG GAA AAA CTG ATA AAG TAT GCA ACA GAC AGT GAA ACA GTA 3984Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val5GAA CCT ATT ATC TCA CAG TTG GTG ACA GTG CTT TTG AAA GGT TGC CAA 4032Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln0GAT GCA AAC TCT CAA GCT CGG TTG CTC TGT GGG GAA TGT TTA GGG GAA 4080Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu51360TTG GGG GCG ATA GAT CCA GGT CGA TTA GAT TTC TCA ACA ACT GAA ACT 4128Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr5CAA GGA AAA GAT TTT ACA TTT GTG ACT GGA GTA GAA GAT TCA AGC TTT 4176Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe0GCC TAT GGA TTA TTG ATG GAG CTA ACA AGA GCT TAC CTT GCG TAT GCT 4224Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala5GAT AAT AGC CGA GCT CAA GAT TCA GCT GCC TAT GCC ATT CAG GAG TTG 4272Asp Asn Ser Arg Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu0CTT TCT ATT TAT GAC TGT AGA GAG ATG GAG ACC AAC GGC CCA GGT CAC 4320Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His51440CAA TTG TGG AGG AGA TTT CCT GAG CAT GTT CGG GAA ATA CTA GAA CCT 4368Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro5CAT CTA AAT ACC AGA TAC AAG AGT TCT CAG AAG TCA ACC GAT TGG TCT 4416His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser0GGA GTA AAG AAG CCA ATT TAC TTA AGT AAA TTG GGT AGT AAC TTT GCA 4464Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala5GAA TGG TCA GCA TCT TGG GCA GGT TAT CTT ATT ACA AAG GTT CGA CAT 4512Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His0GAT CTT GCC AGT AAA ATT TTC ACC TGC TGT AGC ATT ATG ATG AAG CAT 4560Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His51520GAT TTC AAA GTG ACC ATC TAT CTT CTT CCA CAT ATT CTG GTG TAT GTC 4608Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val5TTA CTG GGT TGT AAT CAA GAA GAT CAG CAG GAG GTT TAT GCA GAA ATT 4656Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile0ATG GCA GTT CTA AAG CAT GAC GAT CAG CAT ACC ATA AAT ACC CAA GAC 4704Met Ala Val Leu Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp5ATT GCA TCT GAT CTG TGT CAA CTC AGT ACA CAG ACT GTG TTC TCC ATG 4752Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met0CTT GAC CAT CTC ACA CAG TGG GCA AGG CAC AAA TTT CAG GCA CTG AAA 4800Leu Asp His Leu Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys51600GCT GAG AAA TGT CCA CAC AGC AAA TCA AAC AGA AAT AAG GTA GAC TCA 4848Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser5ATG GTA TCT ACT GTG GAT TAT GAA GAC TAT CAG AGT GTA ACC CGT TTT 4896Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe0CTA GAC CTC ATA CCC CAG GAT ACT CTG GCA GTA GCT TCC TTT CGC TCC 4944Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser5AAA GCA TAC ACA CGA GCT GTA ATG CAC TTT GAA TCA TTT ATT ACA GAA 4992Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu0AAG AAG CAA AAT ATT CAG GAA CAT CTT GGA TTT TTA CAG AAA TTG TAT 5040Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr51680GCT GCT ATG CAT GAA CCT GAT GGA GTG GCC GGA GTC AGT GCA ATT AGA 5088Ala Ala Met His Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg5AAG GCA GAA CCA TCT CTA AAA GAA CAG ATC CTT GAA CAT GAA AGC CTT 5136Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu0GGC TTG CTG AGG GAT GCC ACT GCT TGT TAT GAC AGG GCT ATT CAG CTA 5184Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu5GAA CCA GAC CAG ATC ATT CAT TAT CAT GGT GTA GTA AAG TCC ATG TTA 5232Glu Pro Asp Gln Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu0GGT CTT GGT CAG CTG TCT ACT GTT ATC ACT CAG GTG AAT GGA GTG CAT 5280Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His51760GCT AAC AGG TCC GAG TGG ACA GAT GAA TTA AAC ACG TAC AGA GTG GAA 5328Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu5GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG GAA AAC TAT TTG GCA 5376Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala0GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA CTG GGA CAG CTA TTA 5424Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu5TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT TAT GAC TCA CTG AAA 5472Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys0CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA GCT GCA AGC TTT GAA 5520Leu Val Arg Ala Glu Gln Ile VAl Pro Leu Ser Ala Ala Ser Phe Glu51840AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT GTG AGA TTG CAC ATG 5568Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met5TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT TTC CAG CAT TCT CCA 5616Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro0GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG GTA GCT CGA CTA GAA 5664Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu5ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT ATC CTG GCT CTC CGG 5712Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg0AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT TAC AAT GAA ATG GTT 5760Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val51920GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT AGA AAG GCT GGT CAC 5808Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His5CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA GGG GAA TCA CGA CTC 5856His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu0GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC TGG TCC AAG GGT GAT 5904Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp5GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT GTT GAA TTA TGT TTT 5952Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe0CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC ATG TTA ATC CAT GGT 6000Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly52000CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA GAA ACA GCT AAC TTT 6048Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe200520102015GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT GTG ACC GCG TGC CTG 6096Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu202020252030CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC AAG TAC TAT GAC AAA 6144Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys203520402045TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA AAG CAA GGT GAT CTC 6192Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu205020552060ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT CTA CAA TAT GGA AAT 6240Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn2065207020752080CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA ACT CTA TGG CTT GAT 6288Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp208520902095TAT GGT ACA AAG GCA TAT GAA TGG GAA AAA GCT GGC CGC TCC GAT CGT 6336Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg2GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC AAG GTT ATC ACA GAG 6384Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu2CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG ACT GCT TTT TCA CAA 6432His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln2TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA GTT TTT GTT GTC TTG 6480Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val Val Leu22160ATG GAA ATA ATA GCC AAA GTA TTT CTA GCC TAT CCT CAA CAA GCA ATG 6528Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met2TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT CCC ATG CGT GTG AAC 6576Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn2AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT ATG AAA AAA TCC TTA 6624Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu2GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA GAT AAG CTT CTA GAA 6672Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu221022152220TTG TGC AAT AAA CCG GTT GAT GGA AGT AGT TCC ACA TTA AGC ATG AGC 6720Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser2225223022352240ACT CAT TTT AAA ATG CTT AAA AAG CTG GTA GAA GAA GCA ACA TTT AGT 6765Thr His Phe Lys Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser224522502255GAA ATC CTC ATT CCT CTA CAA TCA GTC ATG ATA CCT ACA CTT CCA TCA 6816Glu Ile Leu Ile Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser226022652270ATT CTG GGT ACC CAT GCT AAC CAT GCT AGC CAT GAA CCA TTT CCT GGA 6864Ile Leu Gly Thr His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly227522802285CAT TGG GCC TAT ATT GCA GGG TTT GAT GAT ATG GTG GAA ATT CTT GCT 6911His Trp Ala Tyr Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala229022952300TCT CTT CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG 6961Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys2305231023152320TTC TAC ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT 7006Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys232523302335AGA CTA ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT 7056Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp234023452350GCA GAG TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT 7104Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile235523602365CCA CTA AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT 7151Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala237023752380GGT TTG AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT 7201Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr2385239023952400ATG ACA GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT 7246Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala240524102415TTA TCT GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT 7296Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His242024252430CCT CCT ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA 7344Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr243524402445TCA TGG TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG 7392Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met245024552460TCA ATG GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT 7440Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Ast2465247024752450ATT CTC TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT 7488Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn248524902495TGT CTT TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA 7536Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro250025052510TTT CGC CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA 7584Phe Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr251525202525GAG GGT CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT 7632Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg253025352540GAT CAG CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT 7680Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp2545255025552560CCT CTT GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA 7725Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro256525702575CTG AAT GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT 7776Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val258025852590CTT GAC ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA 7824Leu Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg259526002605GTG ACA GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA 7872Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile261026152620CAA GAA GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG 7920Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp2625263026352640ACT CCA TAT ATG TGA 7935Thr Pro Tyr Met(2)SEQ ID NO29的說明(i)序列特征(A)長度2644個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型蛋白(xi)序列描述SEQ ID NO29Met Gly Glu His Gly Leu Glu Leu Ala Ser Met Ile Pro Ala Leu Arg1 5 10 15Glu Leu Gly Ser Ala Thr Pro Glu Glu Tyr Asn Thr Val Val Gln Lys20 25 30Pro Arg Gln Ile Leu Cys Gln Phe Ile Asp Arg Ile Leu Thr Asp Val35 40 45Asn Val Val Ala Val Glu Leu Val Lys Lys Thr Asp Ser Gln Pro Thr50 55 60Ser Val Met Leu Leu Asp Phe Ile Gln His Ile Met Lys Ser Ser Pro65 70 75 80Leu Met Phe Val Asn Val Ser Gly Ser His Glu Arg Lys Gly Ser Cys85 90 95Ile Glu Phe Ser Asn Trp Ile Ile Thr Arg Leu Leu Arg Ile Ala Ala100 105 110Thr Pro Ser Cys His Leu Leu His Lys Lys Ile Cys Glu Val Ile Cys115 120 125Ser Leu Leu Phe Leu Phe Lys Ser Lys Ser Pro Ala Ile Phe Gly Val130 135 140Leu Thr Lys Glu Leu Leu Gln Leu Phe Glu Asp Leu Val Tyr Leu His145 150 155 160Arg Arg Asn Val Met Gly His Ala Val Glu Trp Pro Val Val Met Ser165 170 175Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala180 185 190Pro Leu Gln Leu Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr195 200 205Leu Leu Met Val Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg210 215 220Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly225 230 235 240Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe245 250 255Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser260 265 270Phe Leu Glu Leu Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu275 280 285Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro290 295 300Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met305 310 315 320Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg325 330 335Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr340 345 350Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg355 360 365Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly370 375 380Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu385 390 395 400Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln405 410 415Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg420 425 430Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr435 440 445Glu Glu Ile Lys His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser450 455 460Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser465 470 475 480Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val485 490 495Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met500 505 510Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro515 520 525Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu530 535 540Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu545 550 555 560Ala Thr Ile Asp Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met565 570 575Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly580 585 590Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu595 600 605Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile610 615 620Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu625 630 635 640Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr645 650 655Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val660 665 670Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val675 680 685Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys690 695 700Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly705 710 715 720Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly725 730 735His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu740 745 750Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe755 760 765Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp770 775 780Asn Leu His His Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr785 790 795 800Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro805 810 815Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu820 825 830Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu835 840 845Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu850 855 860Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala865 870 875 880Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu885 890 895Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg900 905 910Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln915 920 925Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser930 935 940Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg945 950 955 960Lys Gln Asp Val Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser965 970 975Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr980 985 990Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro995 10001005Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn0Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu51040Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu5Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe0Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln5Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp0Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala51120Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met5Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu0Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser5Ser Val Arg Val Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe0Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val51200Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile5Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala0Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe5Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile0Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp51280Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn5Val Asp Val Arg Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr0Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val5Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln0Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu51360Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr5Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe0Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala5Asp Asn Ser Arg Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu0Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His51440Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro5His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser0Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala5Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His0Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His51520Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val5Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile0Met Ala Val Leu Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp5Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met0Leu Asp His Leu Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys51600Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser5Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe0Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser5Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu0Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr51680Ala Ala Met His Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg5Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu0Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu5Glu Pro Asp Gln Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu0Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His51760Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu5Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala0Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu5Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys0Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu51840Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met5Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro0Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu5Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg0Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val51920Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His5His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu0Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp5Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe0Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly52000Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe200520102015Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu202020252030Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys Tys Tyr Asp Lys203520402045Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu205020552060Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asp2065207020752050Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp208520902095Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg2Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu2His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln2Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val Val Leu22160Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met2Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn2Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu2Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu221022152220Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser2225223022352240Thr His Phe Lys Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser224522502255Glu Ile Leu Ile Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser226022652270Ile Leu Gly Thr His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly227522802285His Trp Ala Tyr Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala229022952300Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys2305231023152320Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys232523302335Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp234023452350Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile235523602365Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala237023752380Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr2385239023952400Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala240524102415Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His242024252430Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr243524402445Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met245024552460Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn2465247024752480Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn248524902495Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro250025052510Phe Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr251525202525Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg253025352540Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp2545255025552560Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro256525702575Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val258025852590Leu Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg259526002605Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile261026152620Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp2625263026352640Thr Pro Tyr Met(2)SEQ ID NO30的說明(i)序列特征(A)長度7624個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型cDNA(ix)特征(A)姓名/符號CDS(B)位置333..7562(xi)序列描述SEQ ID NO30CTTGTGAAGA GAATGTTTTA CACTCTTGTT AGTGAAGTTT ATTCTTTAAA AGTCAATCGT60CAAGGATTTA GCAAATGAAT TAGCACTTCG GATATACTTG TTTATTTAAT ATCTTTTTTG120TTTATTTCAA AGAATTCAGT AATTGGATCA TAACGAGACT TCTGCGGATT GCAGCAACTC180CCTCCTGTCA TTTGTTACAC AAGAAAATCT GTGAAGTCAT CTGTTGATTA TTATTTCTTT240TTAAAAGCAA GAGTCCTGCT ATTTTTGGGG TACTCACAAA AGAATTATTA CAACTTTTTG300AAGACTTGGT TTACCTCCAT AGAAGAAATG TG ATG GGT CAT GCT GTG GAA TGG 353Met Gly His Ala Val Glu Trp1 5CCA GTG GTC ATG AGC CGA TTT TTA AGT CAA TTA GAT GAA CAC ATG GGA 401Pro Val Val Met Ser Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly10 15 20TAT TTA CAA TCA GCT CCT TTG CAG TTG ATG AGT ATG CAA AAT TTA GAA 449Tyr Leu Gln Ser Ala Pro Leu Gln Leu Met Ser Met Gln Asn Leu Glu25 30 35TTT ATT GAA GTC ACT TTA TTA ATG GTT CTT ACT CGT ATT ATT GCA ATT 497Phe Ile Glu Val Thr Leu Leu Met Val Leu Thr Arg Ile Ile Ala Ile40 45 50 55GTG TTT TTT AGA AGG CAA GAA CTC TTA CTT TGG CAG ATA GGT TGT GTT 545Val Phe Phe Arg Arg Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val60 65 70CTG CTA GAG TAT GGT AGT CCA AAA ATT AAA TCC CTA GCA ATT AGC TTT 593Leu Leu Glu Tyr Gly Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe75 80 85TTA ACA GAA CTT TTT CAG CTT GGA GGA CTA CCA GCA CAA CCA GCT AGC 641Leu Thr Glu Leu Phe Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser90 95 100ACT TTT TTC AGC TCA TTT TTG GAA TTA TTA AAA CAC CTT GTA GAA ATG 689Thr Phe Phe Ser Ser Phe Leu Glu Leu Leu Lys His Leu Val Glu Met105 110 115GAT ACT GAC CAA TTG AAA CTC TAT GAA GAG CCA TTA TCA AAG CTG ATA 737Asp Thr Asp Gln Leu Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile120 125 130 135AAG ACA CTA TTT CCC TTT GAA GCA GAA GCT TAT AGA AAT ATT GAA CCT 785Lys Thr Leu Phe Pro Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro140 145 150GTC TAT TTA AAT ATG CTG CTG GAA AAA CTC TGT GTC ATG TTT GAA GAC 833Val Tyr Leu Asn Met Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp155 160 165GGT GTG CTC ATG CGG CTT AAG TCT GAT TTG CTA AAA GCA GCT TTG TGC 881Gly Val Leu Met Arg Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys170 175 180CAT TTA CTG CAG TAT TTC CTT AAA TTT GTG CCA GCT GGG TAT GAA TCT 929His Leu Leu Gln Tyr Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser185 190 195GCT TTA CAA GTC AGG AAG GTC TAT GTG AGA AAT ATT TGT AAA GCT CTT 977Ala Leu Gln Val Arg Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu200 205 210 215TTG GAT GTG CTT GGA ATT GAG GTA GAT GCA GAG TAC TTG TTG GGC CCA 1025Leu Asp Val Leu Gly Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro220 225 230CTT TAT GCA GCT TTG AAA ATG GAA AGT ATG GAA ATC ATT GAG GAG ATT 1073Leu Tyr Ala Ala Leu Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile235 240 245CAA TGC CAA ACT CAA CAG GAA AAC CTC AGC AGT AAT AGT GAT GGA ATA 1121Gln Cys Gln Thr Gln Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile250 255 260TCA CCC AAA AGG CGT CGT CTC AGC TCG TCT CTA AAC CCT TCT AAA AGA 1169Ser Pro Lys Arg Arg Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg265 270 275GCA CCA AAA CAG ACT GAG GAA ATT AAA CAT GTG GAC ATG AAC CAA AAG 1217Ala Pro Lys Gln Thr Glu Glu Ile Lys His Val Asp Met Asn Gln Lys280 285 290 295AGC ATA TTA TGG AGT GCA CTG AAA CAG AAA GCT GAA TCC CTT CAG ATT 1265Ser Ile Leu Trp Ser Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile300 305 310TCC CTT GAA TAC AGT GGC CTA AAG AAT CCT GTT ATT GAG ATG TTA GAA 1313Ser Leu Glu Tyr Ser Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu315 320 325GGA ATT GCT GTT GTC TTA CAA CTG ACT GCT CTG TGT ACT GTT CAT TGT 1361Gly Ile Ala Val Val Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys330 335 340TCT CAT CAA AAC ATG AAC TGC CGT ACT TTC AAG GAC TGT CAA CAT AAA 1409Ser His Gln Asn Met Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys345 350 355TCC AAG AAG AAA CCT TCT GTA GTG ATA ACT TGG ATG TCA TTG GAT TTT 1457Ser Lys Lys Lys Pro Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe360 365 370 375TAC ACA AAA GTG CTT AAG AGC TGT AGA AGT TTG TTA GAA TCT GTT CAG 1505Tyr Thr Lys Val Leu Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln380 385 390AAA CTG GAC CTG GAG GCA ACC ATT GAT AAG GTG GTG AAA ATT TAT GAT 1553Lys Leu Asp Leu Glu Ala Thr Ile Asp Lys Val Val Lys Ile Tyr Asp395 400 405GCT TTG ATT TAT ATG CAA GTA AAC AGT TCA TTT GAA GAT CAT ATC CTG 1601Ala Leu Ile Tyr Met Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu410 415 420GAA GAT TTA TGT GGA ATG CTC TCA CTT CCA TGG ATT TAT TCC CAT TCT 1649Glu Asp Leu Cys Gly Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser425 430 435GAT GAT GGC TGT TTA AAG TTG ACC ACA TTT GCC GCT AAT CTT CTA ACA 1697Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr440 445 450 455TTA AGC TGT AGG ATT TCA GAT AGC TAT TCA CCA CAG GCA CAA TCA CGA 1745Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg460 465 470TGT GTG TTT CTT CTG ACT CTG TTT CCA AGA AGA ATA TTC CTT GAG TGG 1793Cys Val Phe Leu Leu Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp475 480 485AGA ACA GCA GTT TAC AAC TGG GCC CTG CAG AGC TCC CAT GAA GTA ATC 1841Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile490 495 500CGG GCT AGT TGT GTT AGT GGA TTT TTT ATC TTA TTG CAG CAG CAG AAT 1889Arg Ala Ser Cys Val Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn505 510 515TCT TGT AAC AGA GTT CCC AAG ATT CTT ATA GAT AAA GTC AAA GAT GAT 1937Ser Cys Asn Arg Val Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp520 525 530 535TCT GAC ATT GTC AAG AAA GAA TTT GCT TCT ATA CTT GGT CAA CTT GTC 1985Ser Asp Ile Val Lys Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val540 545 550TGT ACT CTT CAC GGC ATG TTT TAT CTG ACA AGT TCT TTA ACA GAA CCT 2033Cys Thr Leu His Gly Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro555 560 565TTC TCT GAA CAC GGA CAT GTG GAC CTC TTC TGT AGG AAC TTG AAA GCC 2081Phe Ser Glu His Gly His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala570 575 580ACT TCT CAA CAT GAA TGT TCA TCT TCT CAA CTA AAA GCT TCT GTC TGC 2129Thr Ser Gln His Glu Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys585 590 595AAG CCA TTC CTT TTC CTA CTG AAA AAA AAA ATA CCT AGT CCA GTA AAA 2177Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys600 605 610 615CTT GCT TTC ATA GAT AAT CTA CAT CAT CTT TGT AAG CAT CTT GAT TTT 2225Leu Ala Phe Ile Asp Asn Leu His His Leu Cys Lys His Leu Asp Phe620 625 630AGA GAA GAT GAA ACA GAT GTA AAA GCA GTT CTT GGA ACT TTA TTA AAT 2273Arg Glu Asp Glu Thr Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn635 640 645TTA ATG GAA GAT CCA GAC AAA GAT GTT AGA GTG GCT TTT AGT GGA AAT 2321Leu Met Glu Asp Pro Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn650 655 660ATC AAG CAC ATA TTG GAA TCC TTG GAC TCT GAA GAT GGA TTT ATA AAG 2369Ile Lys His Ile Leu Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys665 670 675GAG CTT TTT GTC TTA AGA ATG AAG GAA GCA TAT ACA CAT GCC CAA ATA 2417Glu Leu Phe Val Leu Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile680 685 690 695TCA AGA AAT AAT GAG CTG AAG GAT ACC TTG ATT CTT ACA ACA GGG GAT 2465Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp700 705 710ATT GGA AGG GCC GCA AAA GGA GAT TTG GTA CCA TTT GCA CTC TTA CAC 2513Ile Gly Arg Ala Ala Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His715 720 725TTA TTG CAT TGT TTG TTA TCC AAG TCA GCA TCT GTC TCT GGA GCA GCA 2561Leu Leu His Cys Leu Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala730 735 740TAC ACA GAA ATT AGA GCT CTG GTT GCA GCT AAA AGT GTT AAA CTG CAA 2609Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln745 750 755AGT TTT TTC AGC CAG TAT AAG AAA CCC ATC TGT CAG TTT TTG GTA GAA 2657Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu760 765 770 775TCC CTT CAC TCT AGT CAG ATG ACA GCA CTT CCG AAT ACT CCA TGC CAG 2705Ser Leu His Ser Ser Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln780 785 790AAT GCT GAC GTG CGA AAA CAA GAT GTG GCT CAC CAG AGA GAA ATG GCT 2753Asn Ala Asp Val Arg Lys Gln Asp Val Ala His Gln Arg Glu Met Ala795 800 805TTA AAT ACG TTG TCT GAA ATT GCC AAC GTT TTC GAC TTT CCT GAT CTT 2801Leu Asn Thr Leu Ser Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu810 815 820AAT CGT TTT CTT ACT AGG ACA TTA CAA GTT CTA CTA CCT GAT CTT GCT 2849Asn Arg Phe Leu Thr Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala825 830 835GCC AAA GCA AGC CCT GCA GCT TCT GCT CTC ATT CGA ACT TTA GGA AAA 2897Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys840 845 850 855CAA TTA AAT GTC AAT CGT AGA GAG ATT TTA ATA AAC AAC TTC AAA TAT 2945Gln Leu Asn Val Asn Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr860 865 870ATT TTT TCT CAT TTG GTC TGT TCT TGT TCC AAA GAT GAA TTA GAA CGT 2993Ile Phe Ser His Leu Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg875 880 885GCC CTT CAT TAT CTG AAG AAT GAA ACA GAA ATT GAA CTG GGG AGC CTG 3041Ala Leu His Tyr Leu Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu890 895 900TTG AGA CAA GAT TTC CAA GGA TTG CAT AAT GAA TTA TTG CTG CGT ATT 3089Leu Arg Gln Asp Phe Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile905 910 915GGA GAA CAC TAT CAA CAG GTT TTT AAT GGT TTG TCA ATA CTT GCC TCA 3137Gly Glu His Tyr Gln Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser920 925 930 935TTT GCA TCC AGT GAT GAT CCA TAT CAG GGC CCG AGA GAT ATC ATA TCA 3185Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser940 945 950CCT GAA CTG ATG GCT GAT TAT TTA CAA CCC AAA TTG TTG GGC ATT TTG 3233Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu955 960 965GCT TTT TTT AAC ATG CAG TTA CTG AGC TCT AGT GTT GGC ATT GAA GAT 3281Ala Phe Phe Asn Met Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp970 975 980AAG AAA ATG GCC TTG AAC AGT TTG ATG TCT TTG ATG AAG TTA ATG GGA 3329Lys Lys Met Ala Leu Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly985 990 995CCC AAA CAT GTC AGT TCT GTG AGG GTG AAG ATG ATG ACC ACA CTG AGA 3377Pro Lys His Val Ser Ser Val Arg Val Lys Met Met Thr Thr Leu Arg01015ACT GGC CTT CGA TTC AAG GAT GAT TTT CCT GAA TTG TGT TGC AGA GCT 3425Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala0TGG GAC TGC TTT GTT CGC TGC CTG GAT CAT GCT TGT CTG GGC TCC CTT 3473Trp Asp Cys Phe Val Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu5CTC AGT CAT GTA ATA GTA GCT TTG TTA CCT CTT ATA CAC ATC CAG CCT 5521Leu Ser His Val Ile Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro0AAA GAA ACT GCA GCT ATC TTC CAC TAC CTC ATA ATT GAA AAC AGG GAT 3569Lys Glu Thr Ala Ala Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp5GCT GTG CAA GAT TTT CTT CAT GAA ATA TAT TTT TTA CCT GAT CAT CCA 3617Ala Val Gln Asp Phe Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro01095GAA TTA AAA AAG ATA AAA GCC GTT CTC CAG GAA TAC AGA AAG GAG ACC 3665Glu Leu Lys Lys Ile Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr0TCT GAG AGC ACT GAT CTT CAG ACA ACT CTT CAG CTC TCT ATG AAG GCC 3713Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala5ATT CAA CAT GAA AAT GTC GAT GTT CGT ATT CAT GCT CTT ACA AGC TTG 3762Ile Gln His Glu Asn Val Asp Val Arg Ile His Ala Leu Thr Ser Leu0AAG GAA ACC TTG TAT AAA AAT CAG GAA AAA CTG ATA AAG TAT GCA ACA 3809Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr5GAC AGT GAA ACA GTA GAA CCT ATT ATC TCA CAG TTG GTG ACA GTG CTT 3857Asp Ser Glu Thr Val Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu01175TTG AAA GGT TGC CAA GAT GCA AAC TCT CAA GCT CGG TTG CTC TGT GGG 3905Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly0GAA TGT TTA GGG GAA TTG GGG GCG ATA GAT CCA GGT CGA TTA GAT TTC 3953Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe5TCA ACA ACT GAA ACT CAA GGA AAA GAT TTT ACA TTT GTG ACT GGA GTA 4001Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val0GAA GAT TCA AGC TTT GCC TAT GGA TTA TTG ATG GAG CTA ACA AGA GCT 4049Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala5TAC CTT GCG TAT GCT GAT AAT AGC CGA GCT CAA GAT TCA GCT GCC TAT 4097Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala Gln Asp Ser Ala Ala Tyr01255GCC ATT CAG GAG TTG CTT TCT ATT TAT GAC TGT AGA GAG ATG GAG ACC 4145Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr0AAC GGC CCA GGT CAC CAA TTG TGG AGG AGA TTT CCT GAG CAT GTT CGG 4193Asn Gly Pro Gly His Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg5GAA ATA CTA GAA CCT CAT CTA AAT ACC AGA TAC AAG AGT TCT CAG AAG 4241Glu Ile Leu Glu Pro His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys0TCA ACC GAT TGG TCT GGA GTA AAG AAG CCA ATT TAC TTA AGT AAA TTG 4289Ser Thr Asp Trp Ser Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu5GGT AGT AAC TTT GCA GAA TGG TCA GCA TCT TGG GCA GGT TAT CTT ATT 4337Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile01335ACA AAG GTT CGA CAT GAT CTT GCC AGT AAA ATT TTC ACC TGC TGT AGC 4385Thr Lys Val Arg His Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser0ATT ATG ATG AAG CAT GAT TTC AAA GTG ACC ATC TAT CTT CTT CCA CAT 4433Ile Met Met Lys His Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His5ATT CTG GTG TAT GTC TTA CTG GGT TGT AAT CAA GAA GAT CAG CAG GAG 4481Ile Leu Val Tyr Val Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu0GTT TAT GCA GAA ATT ATG GCA GTT CTA AAG CAT GAC GAT CAG CAT ACC 4529Val Tyr Ala Glu Ile Met Ala Val Leu Lys His Asp Asp Gln His Thr5ATA AAT ACC CAA GAC ATT GCA TCT GAT CTG TGT CAA CTC AGT ACA CAG 4577Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln01415ACT GTG TTC TCC ATG CTT GAC CAT CTC ACA CAG TGG GCA AGG CAC AAA 4625Thr Val Phe Ser Met Leu Asp His Leu Thr Gln Trp Ala Arg His Lys0TTT CAG GCA CTG AAA GCT GAG AAA TGT CCA CAC AGC AAA TCA AAC AGA 4673Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg5AAT AAG GTA GAC TCA ATG GTA TCT ACT GTG GAT TAT GAA GAC TAT CAG 4721Asn Lys Val Asp Ser Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln0AGT GTA ACC CGT TTT CTA GAC CTC ATA CCC CAG GAT ACT CTG GCA GTA 4769Ser Val Thr Arg Phe Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val5GCT TCC TTT CGC TCC AAA GCA TAC ACA CGA GCT GTA ATG CAC TTT GAA 4617Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu01495TCA TTT ATT ACA GAA AAG AAG CAA AAT ATT CAG GAA CAT CTT GGA TTT 4865Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe0TTA CAG AAA TTG TAT GCT GCT ATG CAT GAA CCT GAT GGA GTG GCC GGA 4913Leu Gln Lys Leu Tyr Ala Ala Met His Glu Pro Asp Gly Val Ala Gly5GTC AGT GCA ATT AGA AAG GCA GAA CCA TCT CTA AAA GAA CAG ATC CTT 4961Val Ser Ala Ile Arg Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu0GAA CAT GAA AGC CTT GGC TTG CTG AGG GAT GCC ACT GCT TGT TAT GAC 5009Glu His Glu Ser Leu Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp5AGG GCT ATT CAG CTA GAA CCA GAC CAG ATC ATT CAT TAC CAT GGT GTA 5057Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile Ile His Tyr His Gly Val01575GTA AAG TCC ATG TTA GGT CTT GGT CAG CTG TCT ACT GTT ATC ACT CAG 5105Val Lys Ser Met Leu Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln0GTG AAT GGA GTG CAT GCT AAC AGG TCC GAG TGG ACA GAT GAA TTA AAC 5153Val Asn Gly Val His Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn5ACG TAC AGA GTG GAA GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG 5201Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val0GAA AAC TAT TTG GCA GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA 5245Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg5CTG GGA CAG CTA TTA TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT 5297Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe01655TAT GAC TCA CTG AAA CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA 5345Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser0GCT GCA AGC TTT GAA AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT 5393Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile5GTG AGA TTG CAC ATG TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT 5441Val Arg Leu His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu0TTC CAG CAT TCT CCA GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG 5489Phe Gln His Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp5GTA GCT CGA CTA GAA ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT 5537Val Ala Arg Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro01735ATC CTG GCT CTC CGG AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT 5585Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp0TAC AAT GAA ATG GTT GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT 5633Tyr Asn Glu Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala5AGA AAG GCT GGT CAC CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA 5681Arg Lys Ala Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala0GGG GAA TCA CGA CTC GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC 5729Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu5TGG TCC AAG GGT GAT GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT 5777Trp Ser Lys Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly01815GTT GAA TTA TGT TTT CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC 5825Val Glu Leu Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn0ATG TTA ATC CAT GGT CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA 5873Met Leu Ile His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu5GAA ACA GCT AAC TTT GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT 5921Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp0GTG ACC GCG TGC CTG CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC 5963Val Thr Ala Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala5AAG TAC TAT GAC AAA TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA 6017Lys Tyr Tyr Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu01895AAG CAA GGT GAT CTC ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT 6065Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser0CTA CAA TAT GGA AAT CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA 6113Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu5ACT CTA TGG CTT GAT TAT GGT ACA AAG GCA TAT GAA TGG GAA AAA GCT 6161Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala0GGC CGC TCC GAT CGT GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC 6209Gly Arg Ser Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn5AAG GTT ATC ACA GAG CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG 6257Lys Val Ile Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu01975ACT GCT TTT TCA CAA TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA 6305Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu0GTT TTT GTT GTC TTG ATG GAA ATA ATA GCC AAA GTA TTT CTA GCC TAT 6353Val Phe Val Val Leu Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr5CCT CAA CAA GCA ATG TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT 6401Pro Gln Gln Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr201020152020CCC ATG CGT GTG AAC AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT 6449Pro Met Arg Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His202520302035ATG AAA AAA TCC TTA GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA 6497Met Lys Lys Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr2040204520502055GAT AAG CTT CTA GAA TTG TGC AAT AAA CCG GTG GAA ATT CTT GCT TCT 6545Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro Val Glu Ile Leu Ala Ser206020652070CTT CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC 6593Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe207520802085TAC ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA 6641Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg209020952100CTA ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA 6689Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala2GAG TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA 6737Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro22135CTA AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT 6785Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly2TTG AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG 6833Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met2ACA GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA 6881Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu2TCT GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT 6929Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro2CCT ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA 6977Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser2200220522102215TGG TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA 7025Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser222022252230ATG GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT 7073Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile223522402245CTC TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT 7121Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys225022552260CTT TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT 7169Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe226522702275CGC CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG 7217Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu2280228522902295GGT CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT 7265Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp230023052310CAG CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT 7313Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro231523202325CTT GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG 7361Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu233023352340AAT GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT 7409Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu234523502355GAC ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG 7457Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val2360236523702375ACA GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA 7505Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln238023852390GAA GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT 7553Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr239524002405CCA TAT ATG TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA 7602Pro Tyr Met2410AGTAAAAAAA AAAAAAAAAA AA 7624(2)SEQ ID NO31的說明(i)序列特征(A)長度2410個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型蛋白(xi)序列描述SEQ ID NO31Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe0Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp51040His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu5Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr0Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile5Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu0Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr51120Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg5Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu0Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile5Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser0Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile51200Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp5Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu0Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg5Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr0Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg51280Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr5Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys0Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala5Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser0Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val51360Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys5Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu0Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp5Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu0Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys51440Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr5Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile0Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr5Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn0Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His51520Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro5Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg0Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln5Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln0Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser51500Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys5Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys0Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys5Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala0Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Gyr51680Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu5Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser0Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn5Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu0Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp51760Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala5Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr0Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala5Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu0Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu51840Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala5Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu0Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met5Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile0Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr51920Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys5Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg0Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr5Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg0Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Met Glu Ile Ile52000Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060Pro Val Glu Ile Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu2065207020752080Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp208520902095Asp Leu Arg Lys Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn2Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile2Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu2Trp Val Asn Asn Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr22160Lys Glu Lys Gly Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met2Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu2Phe Leu Leu Pro Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg2Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys221022152220Arg Ser Thr Ala Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly2225223022352240Asp Arg His Gly Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys224522502255Val His Val Asp Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu226022652270Val Pro Glu Ile Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly227522802285Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val229022952300Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu2305231023152320Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys232523302335Gly His Ser Lys Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu234023452350Lys Ala Lys Thr His Val Leu Asp Ile Glu Gln Arg Leu Gln Gly Val235523602365Ile Lys Thr Arg Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly237023752380His Val His Tyr Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys2385239023952400Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met24052410(2)SEQ ID NO32的說明(i)序列特征(A)長度7502個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型cDNA(ix)特征(A)姓名/符號CDS(B)位置1..7440(xi)序列描述SEQ ID NO32ATG GGT CAT GCT GTG GAA TGG CCA GTG GTC ATG AGC CGA TTT TTA AGT 48Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15CAA TTA GAT GAA CAC ATG GGA TAT TTA CAA TCA GCT CCT TTG GAG TTG 96Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30ATG AGT ATG CAA AAT TTA GAA TTT ATT GAA GTC ACT TTA TTA ATG GTT 144Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45CTT ACT CGT ATT ATT GCA ATT GTG TTT TTT AGA AGG CAA GAA CTC TTA 192Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60CTT TGG CAG ATA GGT TGT GTT CTG CTA GAG TAT GGT AGT CCA AAA ATT 240Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80AAA TCC CTA GCA ATT AGC TTT TTA ACA GAA CTT TTT CAG CTT GGA GGA 288Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95CTA CCA GCA CAA CCA GCT AGC ACT TTT TTC AGC TCA TTT TTG GAA TTA 336Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110TTA AAA CAC CTT GTA GAA ATG GAT ACT GAC CAA TTG AAA CTC TAT GAA 384Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125GAG CCA TTA TCA AAG CTG ATA AAG ACA CTA TTT CCC TTT GAA GCA GAA 432Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140GCT TAT AGA AAT ATT GAA CCT GTC TAT TTA AAT ATG CTG CTG GAA AAA 480Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160CTC TGT GTC ATG TTT GAA GAC GGT GTG CTC ATG CGG CTT AAG TCT GAT 528Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175TTG CTA AAA GCA GCT TTG TGC CAT TTA CTG CAG TAT TTC CTT AAA TTT 576Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190GTG CCA GCT GGG TAT GAA TCT GCT TTA CAA GTC AGG AAG GTC TAT GTG 624Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205AGA AAT ATT TGT AAA GCT CTT TTG GAT GTG CTT GGA ATT GAG GTA GAT 672Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220GCA GAG TAC TTG TTG GGC CCA CTT TAT GCA GCT TTG AAA ATG GAA AGT 720Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240ATG GAA ATC ATT GAG GAG ATT CAA TGC CAA ACT CAA CAG GAA AAC CTC 768Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255AGC AGT AAT AGT GAT GGA ATA TCA CCC AAA AGG CGT CGT CTC AGC TCG 816Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270TCT CTA AAC CCT TCT AAA AGA GCA CCA AAA CAG ACT GAG GAA ATT AAA 864Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285CAT GTG GAC ATG AAC CAA AAG AGC ATA TTA TGG AGT GCA CTG AAA CAG 912His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300AAA GCT GAA TCC CTT CAG ATT TCC CTT GAA TAC AGT GGC CTA AAG AAT 960Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320CCT GTT ATT GAG ATG TTA GAA GGA ATT GCT GTT GTC TTA CAA CTG ACT 1008Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335GCT CTG TGT ACT GTT CAT TGT TCT CAT CAA AAC ATG AAC TGC CGT ACT 1056Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350TTC AAG GAC TGT CAA CAT AAA TCC AAG AAG AAA CCT TCT GTA GTG ATA 1104Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365ACT TGG ATG TCA TTG GAT TTT TAC ACA AAA GTG CTT AAG AGC TGT AGA 1152Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380AGT TTG TTA GAA TCT GTT CAG AAA CTG GAC CTG GAG GCA ACC ATT GAT 1200Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400AAG GTG GTG AAA ATT TAT GAT GCT TTG ATT TAT ATG CAA GTA AAC AGT 1248Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415TCA TTT GAA GAT CAT ATC CTG GAA GAT TTA TGT GGA ATG CTC TCA CTT 1296Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430CCA TGG ATT TAT TCC CAT TCT GAT GAT GGC TGT TTA AAG TTG ACC ACA 1344Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445TTT GCC GCT AAT CTT CTA ACA TTA AGC TGT AGG ATT TCA GAT AGC TAT 1392Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460TCA CCA CAG GCA CAA TCA CGA TGT GTG TTT CTT CTG ACT CTG TTT CCA 1440Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480AGA AGA ATA TTC CTT GAG TGG AGA ACA GCA GTT TAC AAC TGG GCC CTG 1488Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495CAG AGC TCC CAT GAA GTA ATC CGG GCT AGT TGT GTT AGT GGA TTT TTT 1536Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510ATC TTA TTG CAG CAG CAG AAT TCT TGT AAC AGA GTT CCC AAG ATT CTT 1584Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525ATA GAT AAA GTC AAA GAT GAT TCT GAC ATT GTC AAG AAA GAA TTT GCT 1632Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540TCT ATA CTT GGT CAA CTT GTC TGT ACT CTT CAC GGC ATG TTT TAT CTG 1680Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560ACA AGT TCT TTA ACA GAA CCT TTC TCT GAA CAC GGA CAT GTG GAC CTC 1728Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575TTC TGT AGG AAC TTG AAA GCC ACT TCT CAA CAT GAA TGT TCA TCT TCT 1776Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590CAA CTA AAA GCT TCT GTC TGC AAG CCA TTC CTT TTC CTA CTG AAA AAA 1824Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605AAA ATA CCT AGT CCA GTA AAA CTT GCT TTC ATA GAT AAT CTA CAT CAT 1872Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620CTT TGT AAG CAT CTT GAT TTT AGA GAA GAT GAA ACA GAT GTA AAA GCA 1920Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640GTT CTT GGA ACT TTA TTA AAT TTA ATG GAA GAT CCA GAC AAA GAT GTT 1968Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655AGA GTG GCT TTT AGT GGA AAT ATC AAG CAC ATA TTG GAA TCC TTG GAC 2016Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670TCT GAA GAT GGA TTT ATA AAG GAG CTT TTT GTC TTA AGA ATG AAG GAA 2064Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685GCA TAT ACA CAT GCC CAA ATA TCA AGA AAT AAT GAG CTG AAG GAT ACC 2112Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700TTG ATT CTT ACA ACA GGG GAT ATT GGA AGG GCC GCA AAA GGA GAT TTG 2160Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720GTA CCA TTT GCA CTC TTA CAC TTA TTG CAT TGT TTG TTA TCC AAG TCA 2208Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735GCA TCT GTC TCT GGA GCA GCA TAC ACA GAA ATT AGA GCT CTG GTT GCA 2256Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750GCT AAA AGT GTT AAA CTG CAA AGT TTT TTC AGC CAG TAT AAG AAA CCC 2304Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765ATC TGT CAG TTT TTG GTA GAA TCC CTT CAC TCT AGT CAG ATG ACA GCA 2352Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780CTT CCG AAT ACT CCA TGC CAG AAT GCT GAC GTG CGA AAA CAA GAT GTG 2400Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800GCT CAC CAG AGA GAA ATG GCT TTA AAT ACG TTG TCT GAA ATT GCC AAC 2448Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815GTT TTC GAC TTT CCT GAT CTT AAT CGT TTT CTT ACT AGG ACA TTA CAA 2496Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830GTT CTA CTA CCT GAT CTT GCT GCC AAA GCA AGC CCT GCA GCT TCT GCT 2544Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845CTC ATT CGA ACT TTA GGA AAA CAA TTA AAT GTC AAT CGT AGA GAG ATT 2592Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860TTA ATA AAC AAC TTC AAA TAT ATT TTT TCT CAT TTG GTC TGT TCT TGT 2640Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880TCC AAA GAT GAA TTA GAA CGT GCC CTT CAT TAT CTG AAG AAT GAA ACA 2688Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895GAA ATT GAA CTG GGG AGC CTG TTG AGA CAA GAT TTC CAA GGA TTG CAT 2736Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910AAT GAA TTA TTG CTG CGT ATT GGA GAA CAC TAT CAA CAG GTT TTT AAT 2784Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925GGT TTG TCA ATA CTT GCC TCA TTT GCA TCC AGT GAT GAT CCA TAT CAG 2832Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940GGC CCG AGA GAT ATC ATA TCA CCT GAA CTG ATG GCT GAT TAT TTA CAA 2880Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960CCC AAA TTG TTG GGC ATT TTG GCT TTT TTT AAC ATG CAG TTA CTG AGC 2928Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975TCT AGT GTT GGC ATT GAA GAT AAG AAA ATG GCC TTG AAC AGT TTG ATG 2976Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990TCT TTG ATG AAG TTA ATG GGA CCC AAA CAT GTC AGT TCT GTG AGG GTG 3024Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005AAG ATG ATG ACC ACA CTG AGA ACT GGC CTT CGA TTC AAG GAT GAT TTT 3072Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe0CCT GAA TTG TGT TGC AGA GCT TGG GAC TGC TTT GTT CGC TGC CTG GAT 3120Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp51040CAT GCT TGT CTG GGC TCC CTT CTC AGT CAT GTA ATA GTA GCT TTG TTA 3168His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu5CCT CTT ATA CAC ATC CAG CCT AAA GAA ACT GCA GCT ATC TTC CAC TAC 3216Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr0CTC ATA ATT GAA AAC AGG GAT GCT GTG CAA GAT TTT CTT CAT GAA ATA 3264Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile5TAT TTT TTA CCT GAT CAT CCA GAA TTA AAA AAG ATA AAA GCC GTT CTC 3312Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu0CAG GAA TAC AGA AAG GAG ACC TCT GAG AGC ACT GAT CTT CAG ACA ACT 3360Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr51120CTT CAG CTC TCT ATG AAG GCC ATT CAA CAT GAA AAT GTC GAT GTT CGT 3408Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg5ATT CAT GCT CTT ACA AGC TTG AAG GAA ACC TTG TAT AAA AAT CAG GAA 3456Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu0AAA CTG ATA AAG TAT GCA ACA GAC AGT GAA ACA GTA GAA CCT ATT ATC 3504Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile5TCA CAG TTG GTG ACA GTG CTT TTG AAA GGT TGC CAA GAT GCA AAC TCT 3552Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser0CAA GCT CGG TTG CTC TGT GGG GAA TGT TTA GGG GAA TTG GGG GCG ATA 3600Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile51200GAT CCA GGT CGA TTA GAT TTC TCA ACA ACT GAA ACT CAA GGA AAA GAT 3648Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp5TTT ACA TTT GTG ACT GGA GTA GAA GAT TCA AGC TTT GCC TAT GGA TTA 3696Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu0TTG ATG GAG CTA ACA AGA GCT TAC CTT GCG TAT GCT GAT AAT AGC CGA 3744Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg5GCT CAA GAT TCA GCT GCC TAT GCC ATT CAG GAG TTG CTT TCT ATT TAT 3792Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr0GAC TGT AGA GAG ATG GAG ACC AAC GGC CCA GGT CAC CAA TTG TGG AGG 3840Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg51280AGA TTT CCT GAG CAT GTT CGG GAA ATA CTA GAA CCT CAT CTA AAT ACC 3888Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr5AGA TAC AAG AGT TCT CAG AAG TCA ACC GAT TGG TCT GGA GTA AAG AAG 3936Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys0CCA ATT TAC TTA AGT AAA TTG GGT AGT AAC TTT GCA GAA TGG TCA GCA 3984Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala5TCT TGG GCA GGT TAT CTT ATT ACA AAG GTT CGA CAT GAT CTT GCC AGT 4032Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser0AAA ATT TTC ACC TGC TGT AGC ATT ATG ATG AAG CAT GAT TTC AAA GTG 4080Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val51360ACC ATC TAT CTT CTT CCA CAT ATT CTG GTG TAT GTC TTA CTG GGT TGT 4128Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys5AAT CAA GAA GAT CAG CAG GAG GTT TAT GCA GAA ATT ATG GCA GTT CTA 4176Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu0AAG CAT GAC GAT CAG CAT ACC ATA AAT ACC CAA GAC ATT GCA TCT GAT 4224Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp5CTG TGT CAA CTC AGT ACA CAG ACT GTG TTC TCC ATG CTT GAC CAT CTC 4272Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu0ACA CAG TGG GCA AGG CAC AAA TTT CAG GCA CTG AAA GCT GAG AAA TGT 4320Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys51440CCA CAC AGC AAA TCA AAC AGA AAT AAG GTA GAC TCA ATG GTA TCT ACT 4368Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr5GTG GAT TAT GAA GAC TAT CAG AGT GTA ACC CGT TTT CTA GAC CTC ATA 4416Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile0CCC CAG GAT ACT CTG GCA GTA GCT TCC TTT CGC TCC AAA GCA TAC ACA 4464Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr5CGA GCT GTA ATG CAC TTT GAA TCA TTT ATT ACA GAA AAG AAG CAA AAT 4512Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn0ATT CAG GAA CAT CTT GGA TTT TTA CAG AAA TTG TAT GCT GCT ATG CAT 4560Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His51520GAA CCT GAT GGA GTG GCC GGA GTC AGT GCA ATT AGA AAG GCA GAA CCA 4609Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro5TCT CTA AAA GAA CAG ATC CTT GAA CAT GAA AGC CTT GGC TTG CTG AGG 4656Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg0GAT GCC ACT GCT TGT TAT GAC AGG GCT ATT CAG CTA GAA CCA GAC CAG 4704Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln5ATC ATT CAT TAC CAT GGT GTA GTA AAG TCC ATG TTA GGT CTT GGT CAG 4752Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln0CTG TCT ACT GTT ATC ACT CAG GTG AAT GGA GTG CAT GCT AAC AGG TCC 4800Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser51600GAG TGG ACA GAT GAA TTA AAC ACG TAC AGA GTG GAA GCA GCT TGG AAA 4848Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys5TTG TCA CAG TGG GAT TTG GTG GAA AAC TAT TTG GCA GCA GAT GGA AAA 4896Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys0TCT ACA ACA TGG AGT GTC AGA CTG GGA CAG CTA TTA TTA TCA GCC AAA 4944Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys5AAA AGA GAT ATC ACA GCT TTT TAT GAC TCA CTG AAA CTA GTG AGA GCA 4992Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala0GAA CAA ATT GTA CCT CTT TCA GCT GCA AGC TTT GAA AGA GGC TCC TAC 5040Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr51680CAA CGA GGA TAT GAA TAT ATT GTG AGA TTG CAC ATG TTA TGT GAG TTG 5088Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu5GAG CAT AGC ATC AAA CCA CTT TTC CAG CAT TCT CCA GGT GAC AGT TCT 5136Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser0CAA GAA GAT TCT CTA AAC TGG GTA GCT CGA CTA GAA ATG ACC CAG AAT 5184Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn5TCC TAC AGA GCC AAG GAG CCT ATC CTG GCT CTC CGG AGG GCT TTA CTA 5232Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu0AGC CTC AAC AAA AGA CCA GAT TAC AAT GAA ATG GTT GGA GAA TGC TGG 5280Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp51760CTG CAG AGT GCC AGG GTA GCT AGA AAG GCT GGT CAC CAC CAG ACA GCC 5328Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala5TAC AAT GCT CTC CTT AAT GCA GGG GAA TCA CGA CTC GCT GAA CTG TAC 5376Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr0GTG GAA AGG GCA AAG TGG CTC TGG TCC AAG GGT GAT GTT CAC CAG GCA 5424Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala5CTA ATT GTT CTT CAA AAA GGT GTT GAA TTA TGT TTT CCT GAA AAT GAA 5472Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu0ACC CCA CCT GAG GGT AAG AAC ATG TTA ATC CAT GGT CGA GCT ATG CTA 5520Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu51840CTA GTG GGC CGA TTT ATG GAA GAA ACA GCT AAC TTT GAA AGC AAT GCA 5568Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala5ATT ATG AAA AAA TAT AAG GAT GTG ACC GCG TGC CTG CCA GAA TGG GAG 5616Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu0GAT GGG CAT TTT TAC CTT GCC AAG TAC TAT GAC AAA TTG ATG CCC ATG 5664Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met5GTC ACA GAC AAC AAA ATG GAA AAG CAA GGT GAT CTC ATC CGG TAT ATA 5712Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile0GTT CTT CAT TTT GGC AGA TCT CTA CAA TAT GGA AAT CAG TTC ATA TAT 5760Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr51920CAG TCA ATG CCA CGA ATG TTA ACT CTA TGG CTT GAT TAT GGT ACA AAG 5808Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys5GCA TAT GAA TGG GAA AAA GCT GGC CGC TCC GAT CGT GTA CAA ATG AGG 5656Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg0AAT GAT TTG GGT AAA ATA AAC AAG GTT ATC ACA GAG CAT ACA AAC TAT 5904Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr5TTA GCT CCA TAT CAA TTT TTG ACT GCT TTT TCA CAA TTG ATC TCT CGA 5952Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg0ATT TGT CAT TCT CAC GAT GAA GTT TTT GTT GTC TTG ATG GAA ATA ATA 6000Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Met Glu Ile Ile52000GCC AAA GTA TTT CTA GCC TAT CCT CAA CAA GCA ATG TGG ATG ATG ACA 6048Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015GCT GTG TCA AAG TCA TCT TAT CCC ATG CGT GTG AAC AGA TGC AAG GAA 6096Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030ATC CTC AAT AAA GCT ATT CAT ATG AAA AAA TCC TTA GAG AAG TTT GTT 6144Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045GGA GAT GCA ACT CGC CTA ACA GAT AAG CTT CTA GAA TTG TGC AAT AAA 6192Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060CCG GTT GAT GGA AGT AGT TCC ACA TTA AGC ATG AGC ACT CAT TTT AAA 6240Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys2065207020752080ATG CTT AAA AAG CTG GTA GAA GAA GCA ACA TTT AGT GAA ATC CTC ATT 6268Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile208520902095CCT CTA CAA TCA GTC ATG ATA CCT ACA CTT CCA TCA ATT CTG GGT ACC 6336Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr2CAT GCT AAC CAT GCT AGC CAT GAA CCA TTT CCT GGA CAT TGG GCC TAT 6364His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr2ATT GCA GGG TTT GAT GAT ATG GTG GAA ATT CTT GCT TCT CTT CAG AAA 6432Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys2CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC TAC ATC ATG 6480Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met22160ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA CTA ATG GAA 6528Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu2TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA GAG TCT CGT 6576Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg2AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA CTA AAT GAT 6624Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp2GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT TTG AGA CCT 6672Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro221022152220ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG ACA GGA AAA 6720Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys2225223022352240GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA TCT GAA AAA 6768Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys224522502255CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT CCT ATT TTT 6816Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe226022652270CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA TGG TAC AGT 6864His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser227522802285AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA ATG GTT GGT 6912Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly229022952300TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT CTC TTT GAT 6960Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp2305231023152320TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT CTT TTC AAT 7008Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn232523302335AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT CGC CTG ACT 7056Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr234023452350CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG GGT CTT TTT 7104His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe235523602365CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CTG GAT CAG CGA GAG 7152Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu237023752380CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT CTT GTG GAA 7200Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu2385239023952400TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG AAT GAA ACT 7148Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Let Asn Glu Thr240524102415GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT GAC ATT GAG 7196Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu242024252430CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG ACA GGA CTG 7346Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu243524402445CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA GAA GCT ACT 7332Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr245024552460GAT GAA AAC TTA CTA TGC ACG ATG TAT CTT GGT TGG ACT CCA TAT ATG 7440Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met2465247024752480TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA AGTAAAAAAA AAAAAAAAAA7510AA 7512(2)SEQ ID NO33的說明(i)序列特征(A)長度2480個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型蛋白(xi)序列描述SEQ ID NO33Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895Glu Ile Glu Leu Gly Ser Leu Leu Arg Glu Asp Phe Gln Gly Leu His900 905 910Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe0Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp51040His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu5Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr0Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile5Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu0Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr51120Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg5Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu0Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile5Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser0Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile51200Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp5Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu0Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg5Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr0Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg51280Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr5Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys0Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala5Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser0Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val51360Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys5Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu0Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp5Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu0Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys51440Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr5Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile0Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr5Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn0Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His51520Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro5Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg0Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln5Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Glnl57015751580Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg ser51600Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys5Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys0Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys5Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala0Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr51680Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu5Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser0Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn5Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu0Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp51760Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala5Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr0Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala5Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu0Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu51840Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala5Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu0Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met5Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile0Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr51920Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys5Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg0Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr5Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg0Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Met Glu Ile Ile52000Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045Gly Asp Ala Thr Arg Leu Thr Asp Lys Let Leu Glu Leu Cys Asn Lys205020552060Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys2065207020752080Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile208520902095Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr2His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr2Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys2Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met22160Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu2Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg2Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp2Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro221022152220Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys2225223022352240Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys224522502255Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe226022652270His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser227522802285Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly229022952300Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp2305231023152320Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn232523302335Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr234023452350His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe235523602365Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu237023752380Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu2385239023952400Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr240524102415Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu242024252430Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu243524402445Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr245024552460Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met2465247024752480(2)SEQ ID NO34的說明(i)序列特征(A)長度9385個堿基對(B)類型核苷酸(C)鏈型單鏈(D)拓撲結構線性(ii)分子類型cDNA(ix)特征(A)姓名/符號CDS(B)位置190..9357(xi)序列描述SEQ ID NO34GCGAGAGGAG TCGGGATCTG CGCTGCAGCC ACCGCCGCGG TTGATACTAC TTTGACCTTC60CGAGTGCAGT GAGGCATACA TCACAATTTG GAATTATGCA TTGGTTTATC AATTTACTTG120TTTATTGTCA CCCTGCTGCC CAGATATGAC TTCATGAGGA CAGTGATGTG TGTTCTGAAA180TTGTGAACC ATG AGT CTA GTA CTT AAT GAT CTG CTT ATC TGC TGC CGT228Met Ser Leu Val Leu Asn Asp Leu Leu Ile Cys Cys Arg1 5 10CAA CTA GAA CAT GAT AGA GCT ACA GAA CGA AAG AAA GAA GTT GAG AAA 276Gln Leu Glu His Asp Arg Ala Thr Glu Arg Lys Lys Glu Val Glu Lys15 20 25TTT AAG CGC CTG ATT CGA GAT CCT GAA ACA ATT AAA CAT CTA GAT CGG 324Phe Lys Arg Leu Ile Arg Asp Pro Glu Thr Ile Lys His Leu Asp Arg30 35 40 45CAT TCA GAT TCC AAA CAA GGA AAA TAT TTG AAT TGG GAT GCT GTT TTT 372His Ser Asp Ser Lys Gln Gly Lys Tyr Leu Asn Trp Asp Ala Val Phe50 55 60AGA TTT TTA CAG AAA TAT ATT CAG AAA GAA ACA GAA TGT CTG AGA ATA 420Arg Phe Leu Gln Lys Tyr Ile Gln Lys Glu Thr Glu Cys Leu Arg Ile65 70 75GCA AAA CCA AAT GTA TCA GCC TCA ACA CAA GCC TCC AGG CAG AAA AAG 468Ala Lys Pro Asn Val Ser Ala Ser Thr Gln Ala Ser Arg Gln Lys Lys80 85 90ATG CAG GAA ATC AGT AGT TTG GTC AAA TAC TTC ATC AAA TGT GCA AAC 516Met Gln Glu Ile Ser Ser Leu Val Lys Tyr Phe Ile Lys Cys Ala Asn95 100 105AGA AGA GCA CCT AGG CTA AAA TGT CAA GAA CTC TTA AAT TAT ATC ATG 564Arg Arg Ala Pro Arg Leu Lys Cys Gln Glu Leu Leu Asn Tyr Ile Met110 115 120 125GAT ACA GTG AAA GAT TCA TCT AAT GGT GCT ATT TAC GGA GCT GAT TGT 612Asp Thr Val Lys Asp Ser Ser Asn Gly Ala Ile Tyr Gly Ala Asp Cys130 135 140AGC AAC ATA CTA CTC AAA GAC ATT CTT TCT GTG AGA AAA TAC TGG TGT 660Ser Asn Ile Leu Leu Lys Asp Ile Leu Ser Val Arg Lys Tyr Trp Cys145 150 155GAA ATA TCT CAG CAA CAG TGG TTA GAA TTG TTC TCT GTG TAC TTC AGG 708Glu Ile Ser Gln Gln Gln Trp Leu Glu Leu Phe Ser Val Tyr Phe Arg160 165 170CTC TAT CTG AAA CCT TCA CAA GAT GTT CAT AGA GTT TTA GTG GCT AGA 756Leu Tyr Leu Lys Pro Ser Gln Asp Val His Arg Val Leu Val Ala Arg175 180 185ATA ATT CAT GCT GTT ACC AAA GGA TGC TGT TCT CAG ACT GAC GGA TTA 804Ile Ile His Ala Val Thr Lys Gly Cys Cys Ser Gln Thr Asp Gly Leu190 195 200 205AAT TCC AAA TTT TTG GAC TTT TTT TCC AAG GCT ATT CAG TGT GCG AGA 852Asn Ser Lys Phe Leu Asp Phe Phe Ser Lys Ala Ile Gln Cys Ala Arg210 215 220CAA GAA AAG AGC TCT TCA GGT CTA AAT CAT ATC TTA GCA GCT CTT ACT 900Gln Glu Lys Ser Ser Ser Gly Leu Asn His Ile Leu Ala Ala Leu Thr225 230 235ATC TTC CTC AAG ACT TTG GCT GTC AAC TTT CGA ATT CGA GTG TGT GAA 948Ile Phe Leu Lys Thr Leu Ala Val Asn Phe Arg Ile Arg Val Cys Glu240 245 250TTA GGA GAT GAA ATT CTT CCC ACT TTG CTT TAT ATT TGG ACT CAA CAT 996Leu Gly Asp Glu Ile Leu Pro Thr Leu Leu Tyr Ile Trp Thr Gln His255 260 265AGG CTT AAT GAT TCT TTA AAA GAA GTC ATT ATT GAA TTA TTT CAA CTG 1044Arg Leu Asn Asp Ser Leu Lys Glu Val Ile Ile Glu Leu Phe Gln Leu270 275 280 285CAA ATT TAT ATC CAT CAT CCG AAA GGA GCC AAA ACC CAA GAA AAA GGT 1092Gln Ile Tyr Ile His His Pro Lys Gly Ala Lys Thr Gln Glu Lys Gly290 295 300GCT TAT GAA TCA ACA AAA TGG AGA AGT ATT TTA TAC AAC TTA TAT GGT 1140Ala Tyr Glu Ser Thr Lys Trp Arg Ser Ile Leu Tyr Ast Leu Tyr Asp305 310 315CTG CTA GTG AAT GAG ATA AGT CAT ATA GGA AGT AGA GGA AAG TAT TCT 1168Leu Leu Val Asn Glu Ile Ser His Ile Gly Ser Arg Gly Lys Tyr Ser320 325 330TCA GGA TTT CGT AAT ATT GCC GTC AAA GAA AAT TTG ATT GAA TTG ATG 1236Ser Gly Phe Arg Asn Ile Ala Val Lys Glu Asn Leu Ile Glu Leu Met335 340 345GCA GAT ATC TGT CAC CAG GTT TTT AAT GAA GAT ACC AGA TCC TTG GAG 1254Ala Asp Ile Cys His Gln Val Phe Asp Glu Asp Thr Arg Ser Leu Glu350 355 360 365ATT TCT CAA TCT TAC ACT ACT ACA CAA AGA GAA TCT AGT GAT TAC AGT 1332Ile Ser Gln Ser Tyr Thr Thr Thr Gln Arg Glu Ser Ser Asp Tyr Ser370 375 380GTC CCT TGC AAA AGG AAG AAA ATA GAA CTA GGC TGG GAA GTA ATA AAA 1360Val Pro Cys Lys Arg Lys Lys Ile Glu Leu Gly Trp Glu Val Ile Lys385 390 395GAT CAC CTT CAG AAG TCA CAG AAT GAT TTT GAT CTT GTG CCT TGG CCA 1423Asp His Leu Gln Lys Ser Gln Asn Asp Phe Asp Leu Val Pro Trp Leu400 405 410CAG ATT GCA ACC CAA TTA ATA TCA AAG TAT CCT GCA AGT TTA CCT AAC 1475Gln Ile Ala Thr Gln Leu Ile Ser Lys Tyr Pro Ala Ser Leu Pro Asn415 420 425TGT GAG CTG TCT CCA TTA CTG ATG ATA CTA TCT CAG CTT CTA CCC CAA 1524Cys Glu Leu Ser Pro Leu Leu Met Ile Leu Ser Gln Leu Leu Pro Gln430 435 440 445CAG CGA CAT GGG GAA CGT ACA CCA TAT GTG TTA GGA TGC CTT ACG GAA 1572Gln Arg His Gly Glu Arg Thr Pro Tyr Val Leu Arg Cys Leu Thr Glu450 455 460GTT GCA TTG TGT CAA GAC AAG AGG TCA AAC CTA GAA AGC TCA CAA AAG 1622Val Ala Leu Cys Gln Asp Lys Arg Ser Asn Leu Glu Ser Ser Gln Lys465 470 475TCA GAT TTA TTA AAA CTC TGG AAT AAA ATT TGG TGT ATT ACC TTT CGT 1663Ser Asp Leu Leu Lys Leu Trp Asn Lys Ile Trp Cys Ile Thr Phe Arg480 485 490GGT ATA AGT TCT GAG CAA ATA CAA GCT GAA AAC TTT GGC TTA CTT GGA 1716Gly Ile Ser Ser Glu Gln Ile Gln Ala Glu Asn Phe Gly Leu Leu Gly495 500 505GCC ATA ATT CAG GGT AGT TTA GTT GAG GTT GAC AGA GAA TTC TGG AAG 1764Ala Ile Ile Gln Gly Ser Leu Val Glu Val Asp Arg Glu Phe Trp Lys510 515 520 525TTA TTT ACT GGG TCA GCC TGC AGA CCT TCA TGT CCT GCA GTA TGC TGT 1812Leu Phe Thr Gly Ser Ala Cys Arg Pro Ser Cys Pro Ala Val Cys Cys530 535 540TTG ACT TTG GCA CTG ACC ACC AGT ATA GTT CCA GGA GCG GTA AAA ATG 1860Leu Thr Leu Ala Leu Thr Thr Ser Ile Val Pro Gly Ala Val Lys Met545 550 555GGA ATA GAG CAA AAT ATG TGT GAA GTA AAT AGA AGC TTT TCT TTA AAG 1908Gly Ile Glu Gln Asn Met Cys Glu Val Asr Arg Ser Phe Ser Leu Lys560 565 570GAA TCA ATA ATG AAA TGG CTC TTA TTC TAT CAG TTA GAG GGT GAC TTA 1956Glu Ser Ile Met Lys Trp Leu Leu Phe Tyr Gln Leu Glu Gly Asp Leu575 580 585GAA AAT AGC ACA GAA GTG CCT CCA ATT CTT CAC AGT AAT TTT CCT CAT 2004Glu Asn Ser Thr Glu Val Pro Pro Ile Leu His Ser Asn Phe Pro His590 595 600 605CTT GTA CTG GAG AAA ATT CTT GTG AGT CTC ACT ATG AAA AAC GTT AAA 2052Leu Val Leu Glu Lys Ile Leu Val Ser Leu Thr Met Lys Asn Cys Lys610 615 620GCT GCA ATG AAT TTT TTC CAA AGC GTG CCA GAA TGT GAA CAC CAC CAA 2123Ala Ala Met Asn Phe Phe Gln Ser Val Pro Glu Cys Glu His His Gln625 630 635AAA GAT AAA GAA GAA CTT TCA GTC TCA GAA GTA GAA GAA CTA TTT CTT 2143Lys Asp Lys Glu Glu Leu Ser Phe Ser Glu Val Glu Glu Leu The Leu640 645 650CAG ACA ACT TTT GAC AAG ATG GAC TTT TTA ACC ATT GTG AGA GAA TGT 2196Gln Thr Thr Phe Asp Lys Met Asp Phe Leu Thr Ile Val Arg Glu Cys655 660 665GGT ATA GAA AAG CAC CAG TCC AGT ATT GGC TTC TCT GTC CAC CAG AAT 2244Gly Ile Glu Lys His Gln Ser Ser Ile Gly Phe Ser Val His Gln Asn670 675 680 685CTC AAG GAA TCA CTG GAT CGC TGT CTT CTG GGA TTA TCA GAA CAG CTT 2292Leu Lys Glu Ser Leu Asp Arg Cys Leu Leu Gly Leu Ser Glu Gln Leu690 695 700CTG AAT AAT TAC TCA TCT GAG ATT ACA AAT TCA GAA ACT TTT GTC CGG 2343Leu Asn Asn Tyr Ser Ser Glu Ile Thr Asn Ser Glu Thr Leu Val Arg705 710 715TGT TCA CGT CTT TTG GTG GGT GTC CTT GGC GGC TGC TGT TAC ATG GGT 2353Cys Ser Arg Leu Leu Val Gly Val Leu Gly Cys Tyr Cys Tyr Met Gly720 725 730GTA ATA GCT GAA GAG GAA GCA TAT AAG TCA GAA TTA TTC CAG AAA GCT 2436Val Ile Ala Glu Glu Glu Ala Tyr Lys Ser Glu Leu Phe Gln Lys Ala735 740 754AAC TCT CTA ATG CAA TGT GCA GGA GAA AGT ATC ACT CTG TTT AAA AAC 2454Asn Ser Leu Met Gln Cys Ala Gly Glu Ser Ile Thr Leu Phe Lys Asn750 755 760 765AAG ACA AAT GAG GAA TTC AGA ATT GGT TCC TTG AGA AAT ATG ATG CAG 2533Lys Thr Asn Glu Glu Phe Arg Ile Gly Ser Leu Arg Asn Met Met Gln770 775 750CTA TGT ACA CGT TGC TTG AGC AAC TGT ACC AAG AAG AGT CCA AAT AAG 2581Leu Cys Thr Arg Cys Leu Ser Asn Cys Thr Lys Lys Ser Pro Asn Lys785 790 795ATT GCA TCT GGC TTT TTC CTG CGA TTG TTA ACA TCA AAG CTA ATG AAT 2623Ile Ala Ser Gly Phe Phe Leu Arg Leu Leu Thr Ser Lys Leu Met Asn800 805 810GAC ATT GCA GAT ATT TGT AAA AGT TTA GCA TCC TTC ATC AAA AAG CCA 2676Asp Ile Ala Asp Ile Cys Lys Ser Leu Ala Ser Phe Ile Lys Lys Pro815 820 825TTT GAC CGT GGA GAA GTA GAA TCA ATG GAA GAT GAT ACT AAT GGA AAT 2724Phe Asp Arg Gly GLu Val Glu Ser Met Glu Asp Asp Thr Asn Gly Asn830 835 840 845CTA ATG GAG GTG GAG GAT CAG TCA TCC ATG AAT CTA TTT AAC GAT TAC 2772Leu Met Glu Val Glu Asp Gln Ser Ser Met Asn Leu Phe Asn Asp Tyr850 855 860CCT GAT AGT AGT GTT AGT GAT GCA AAC GAA CCT GGA GAG AGC CAA AGT 2820Pro Asp Ser Ser Val Ser Asp Ala Asn Glu Pro Gly Glu Ser Gln Ser865 870 875ACC ATA GGT GCC ATT AAT CCT TTA GCT GAA GAA TAT CTG TCA AAG CAA 2868Thr Ile Gly Ala Ile Asn Pro Leu Ala Glu Glu Tyr Leu Ser Lys Gln880 885 890GAT CTA CTT TTC TTA GAC ATG CTC AAG TTC TTG TGT TTG TGT GTA ACT 2916Asp Leu Leu Phe Leu Asp Met Leu Lys Phe Leu Cys Leu Cys Val Thr895 900 905ACT GCT CAG ACC AAT ACT GTG TCC TTT AGG GCA GCT GAT ATT CGG AGG 2964Thr Ala Gln Thr Asn Thr Val Ser Phe Arg Ala Ala Asp Ile Arg Arg910 915 920 925AAA TTG TTA ATG TTA ATT GAT TCT AGC ACG CTA GAA CCT ACC AAA TCC 3012Lys Leu Leu Met Leu Ile Asp Ser Ser Thr Leu Glu Pro Thr Lys Ser930 935 940CTC CAC CTG CAT ATG TAT CTA ATG CTT TTA AAG GAG CTT CCT GGA GAA 3060Leu His Leu His Met Tyr Leu Met Leu Leu Lys Glu Leu Pro Gly Glu945 950 955GAG TAC CCC TTG CCA ATG GAA GAT GTT CTT GAA CTT CTG AAA CCA CTA 3108Glu Tyr Pro Leu Pro Met Glu Asp Val Leu Glu Leu Leu Lys Pro Leu960 965 970TCC AAT GTG TGT TCT TTG TAT CGT CGT GAC CAA GAT GTT TGT AAA ACT 3156Ser Asn Val Cys Ser Leu Tyr Arg Arg Asp Gln Asp Val Cys Lys Thr975 980 985ATT TTA AAC CAT GTC CTT CAT GTA GTG AAA AAC CTA GGT CAA AGC AAT 3204Ile Leu Asn His Val Leu His Val Val Lys Asn Leu Gly Gln Ser Asn990 995 10001005ATG GAC TCT GAG AAC ACA AGG GAT GCT CAA GGA CAG TTT CTT ACA GTA 3252Met Asp Ser Glu Asn Thr Arg Asp Ala Gln Gly Gln Phe Leu Thr Val0ATT GGA GCA TTT TGG CAT CTA ACA AAG GAG AGG AAA TAT ATA TTC TCT 3300Ile Gly Ala Phe Trp His Leu Thr Lys Glu Arg Lys Tyr Ile Phe Ser5GTA AGA ATG GCC CTA GTA AAT TGC CTT AAA ACT TTG CTT GAG GCT GAT 3348Val Arg Met Ala Leu Val Asn Cys Leu Lys Thr Leu Leu Glu Ala Asp0CCT TAT TCA AAA TGG GCC ATT CTT AAT GTA ATG GGA AAA GAC TTT CCT 3396Pro Tyr Ser Lys Trp Ala Ile Leu Asn Val Met Gly Lys Asp Phe Pro5GTA AAT GAA GTA TTT ACA CAA TTT CTT GCT GAC AAT CAT CAC CAA GTT 3444Val Asn Glu Val Phe Thr Gln Phe Leu Ala Asp Asn His His Gln Val01085CGC ATG TTG GCT GCA GAG TCA ATC AAT AGA TTG TTC CAG GAC ACG AAG 3492Arg Met Leu Ala Ala Glu Ser Ile Asn Arg Leu Phe Gln Asp Thr Lys0GGA GAT TCT TCC AGG TTA CTG AAA GCA CTT CCT TTG AAG CTT CAG CAA 3540Gly Asp Ser Ser Arg Leu Leu Lys Ala Leu Pro Leu Lys Leu Gln Gln5ACA GCT TTT GAA AAT GCA TAC TTG AAA GCT CAG GAA GGA ATG AGA GAA 3555Thr Ala Phe Glu Asn Ala Tyr Leu Lys Ala Gln Glu Gly Met Arg Glu0ATG TCC CAT AGT GCT GAG AAC CCT GAA ACT TTG GAT GAA ATT TAT AAT 3636Met Ser His Ser Ala Glu Asn Pro Glu Thr Leu Asp Glu Ile Tyr Asn5AGA AAA TCT GTT TTA CTG ACG TTG ATA GCT GTG GTT TTA TCC TGT AGC 3654Arg Lys Ser Val Leu Thu Thr Leu Ile Ala Val Val Leu Ser Cys Ser01165CCT ATC TGC GAA AAA CAG GCT TTG TTT GCC CTG TGT AAA TCT GTG AAA 3732Pro Ile Cys Glu Lys Gln Ala Leu Phe Ala Leu Cys Lys Ser Val Lys0GAG AAT GGA TTA GAA CCT CAC CTT GTG AAA AAG GTT TTA GAG AAA GTT 3750Glu Asn Gly Leu Glu Pro His Leu Val Lys Lys Val Leu Glu Lys Val5TCT GAA ACT TTT GGA TAT AGA CGT TTA GAA GAC TTT ATG GCA TCT CAT 3828Ser Glu Thr Phe Gly Tyr Arg Arg Leu Glu Asp Phe Met Ala Ser His0TTA GAT TAT CTG GTT TTG GAA TGG CTA AAT CTT CAA GAT ACT GAA TAC 3876Leu Asp Tyr Leu Val Leu Glu Trp Leu Asn Leu Gln Asp Thr Glu Tyr5AAC TTA TCT TCT TTT CCT TTT ATT TTA TTA AAC TAC ACA AAT ATT GAG 3924Asn Leu Ser Ser Phe Pro Phe Ile Leu Leu Asn Tyr Thr Asn Ile Glu01245GAT TTC TAT AGA TCT TGT TAT AAG GTT TTG ATT CCA CAT CTG GTG ATT 3972Asp Phe Tyr Arg Ser Cys Tyr Lys Val Leu Ile Pro His Leu Val Ile0AGA AGT CAT TTT GAT GAG GTG AAG TCC ATT GTT AAT CAG ATT CAA GAG 4022Arg Ser His Phe Asp Glu Val Lys Ser Ile Ala Asn Gln Ile Gln Glu5GAC TGG AAA AGT CTT CTA ACA GAC TGC TTT CCA AAG ATT CTT GTA AAT 4063Asp Trp Lys Ser Leu Leu Thr Asp Cys Phe Pro Lys Ile Leu Val Asn0ATT CTT CCT TAT TTT GCC TAT GAG GGT ACC AGA GAC AGT GGG ATG GCA 4116Ile Leu Pro Tyr Phe Ala Tyr Glu Gly Thr Arg Asp Ser Gly Met Ala5CAG CAA AGA GAG ACT GCT ACC AAG GTC TAT GAT ATG CTT AAA AGT GAA 4164Gln Gln Arg Glu Ahr Ala Thr Lys Val Tyr Asp Met Leu Lys Ser Glu01325AAC TTA TTG GGA AAA CAG ATT GAT CAC TTA TTC ATT AGT AAT TTA CCA 4211Asn Leu Leu Gly Lys Gln Ile Asp His Leu Phe Ile Ser Asn Leu Pro0GAG ATT GTG GTG GAG TTA TTG ATG ACG TTA CAT GAG CCA GCA AAT TCT 4260Glu Ile Val Val Glu Leu Leu Met Thr Leu His Glu Pro Ala Asp Ser5AGT GCC AGT CAG AGC ACT GAC CTC TGT GAC TTT TCA GGG GAT TTG GAT 4308Ser Ala Ser Gln Ser Thr Asp Leu Cys Asp Phe Ser Gly Asp Leu Asp0CCT GCT CCT AAT CCA CCT CAT TTT CCA TCG CAT GTG ATT AAA GCA ACA 4356Pro Ala Pro Asn Pro Pro His Phe Pro Ser His Val Ile Lys Ala Thr5TTT GCC TAT ATC AGC AAT TGT CAT AAA ACC AAG TTA AAA AGC ATT TTA 4404Phe Ala Tyr Ile Ser Asn Cys His Lys Thr Lys Leu Lys Ser Ile Leu01405GAA ATT CTT TCC AAA AGC CCT GAT TCC TAT CAG AAA ATT CTT CTT GCC 4452Glu Ile Leu Ser Lys Ser Pro Asp Ser Tyr Gln Lys Ile Leu Leu Ala0ATA TGT GAG CAA GCA GCT GAA ACA AAT AAT GTT TAT AAG AAG CAC AGA 4500Ile Cys Glu Gln Ala Ala Glu Thr Asn Asn Val Tyr Lys Lys His Arg5ATT CTT AAA ATA TAT CAC CTG TTT GTT AGT TTA TTA CTG AAA GAT ATA 4548Ile Leu Lys Ile Tyr His Leu Phe Val Ser Leu Leu Leu Lys Asp Ile0AAA AGT GGC TTA GGA GGA GCT TGG GCC TTT GTT CTT CGA GAC GTT ATT 4596Lys Ser Gly Leu Gly Gly Ala Trp Ala Phe Val Leu Arg Asp Val Ile5TAT ACT TTG ATT CAC TAT ATC AAC CAA AGG CCT TCT TGT ATC ATG GAT 4644Tyr Thr Leu Ile His Tyr Ile Asn Gln Arg Pro Ser Cys Ile Met Asp01485GTG TCA TTA CGT AGC TTC TCC CTT TGT TGT GAC TTA TTA AGT CAG GTT 4692Val Ser Leu Arg Ser Phe Ser Leu Cys Cys Asp Leu Leu Ser Gln Val0TGC CAG ACA GCC GTG ACT TAC TGT AAG GAT GCT CTA GAA AAC CAT CTT 4740Cys Gln Thr Ala Val Thr Tyr Cys Lys Asp Ala Leu Glu Asn His Leu5CAT GTT ATT GTT GGT ACA CTT ATA CCC CTT GTG TAT GAG CAG GTG GAG 4788His Val Ile Val Gly Thr Leu Ile Pro Leu Val Tyr Glu Gln Val Glu0GTT CAG AAA CAG GTA TTG GAC TTG TTG AAA TAC TTA GTG ATA GAT AAC 4836Val Gln Lys Gln Val Leu Asp Leu Leu Lys Tyr Leu Val Ile Asp Asn5AAG GAT AAT GAA AAC CTC TAT ATC ACG ATT AAG CTT TTA GAT CCT TTT 4884Lys Asp Asn Glu Asn Leu Tyr Ile Thr Ile Lys Leu Leu Asp Pro Phe01565CCT GAC CAT GTT GTT TTT AAG GAT TTG CGT ATT ACT CAG CAA AAA ATC 4932Pro Asp His Val Val Phe Lys Asp Leu Arg Ile Thr Gln Gln Lys Ile0AAA TAC AGT AGA GGA CCC TTT TCA CTC TTG GAG GAA ATT AAC CAT TTT 4980Lys Tyr Ser Arg Gly Pro Phe Ser Leu Leu Glu Glu Ile Asn His Phe5CTC TCA GTA AGT GTT TAT GAT GCA CTT CCA TTG ACA AGA CTT GAA GGA 5026Leu Ser Val Ser Val Tyr Asp Ala Leu Pro Leu Thr Arg Leu Glu Gly0CTA AAG GAT CTT CGA AGA CAA CTG GAA CTA CAT AAA GAT CAG ATG GTG 5076Leu Lys Asp Leu Arg Arg Gln Leu Glu Leu His Lys Asp Gln Met Val5GAC ATT ATG AGA GCT TCT CAG GAT AAT CCG CAA GAT GGG ATT ATG GTG 5124Asp Ile Met Arg Ala Ser Gln Asp Asn Pro Gln Asp Gly Ile Met Val01645AAA CTA GTT GTC AAT TTG TTG CAG TTA TCC AAG ATG GCA ATA AAC CAC 5172Lys Leu Val Val Asn Leu Leu Gln Leu Ser Lys Met Ala Ile Asn His0ACT GGT GAA AAA GAA GTT CTA GAG GCT GTT GGA AGC TGC TTG GGA GAA 5220Thr Gly Glu Lys Glu Val Leu Glu Ala Val Gly Ser Cys Leu Gly Glu5GTG GGT CCT ATA GAT TTC TCT ACC ATA GCT ATA CAA CAT AGT AAA GAT 5268Val Gly Pro Ile Asp Phe Ser Thr Ile Ala Ile Gln His Ser Lys Asp0GCA TCT TAT ACC AAG GCC CTT AAG TTA TTT GAA GAT AAA GAA CTT CAG 5316Ala Ser Tyr Thr Lys Ala Leu Lys Leu Phe Glu Asp Lys Glu Leu Gln5TGG ACC TTC ATA ATG CTG ACC TAC CTG AAT AAC ACA CTG GTA GAA GAT 5364Trp Thr Phe Ile Met Leu Thr Tyr Leu Asn Asn Thr Leu Val Glu Asp01725TGT GTC AAA GTT CGA TCA GCA GCT GTT ACC TGT TTG AAA AAC ATT TTA 5412Cys Val Lys Val Arg Ser Ala Ala Val Thr Cys Leu Lys Asn Ile Leu0GCC ACA AAG ACT GGA CAT AGT TTC TGG GAG ATT TAT AAG ATG ACA ACA 5460Ala Thr Lys Thr Gly His Ser Phe Trp Glu Ile Tyr Lys Met Thr Thr5GAT CCA ATG CTG GCC TAT CTA CAG CCT TTT AGA ACA TCA AGA AAA AAG 5508Asp Pro Met Leu Ala Tyr Leu Gln Pro Phe Arg Thr Ser Arg Lys Lys0TTT TTA GAA GTA CCC AGA TTT GAC AAA GAA AAC CCT TTT GAA GGC CTG 5556Phe Leu Glu Val Pro Arg Phe Asp Lys Glu Asn Pro Phe Glu Gly Leu5GAT GAT ATA AAT CTG TGG ATT CCT CTA AGT GAA AAT CAT GAC ATT TGG 5604Asp Asp Ile Asn Leu Trp Ile Pro Leu Ser Glu Asn His Asp Ile Trp01805ATA AAG ACA CTG ACT TGT GCT TTT TTG GAC AGT GGA GGC ACA AAA TGT 5652Ile Lys Thr Leu Thr Cys Ala Phe Leu Asp Ser Gly Gly Thr Lys Cys0GAA ATT CTT CAA TTA TTA AAG CCA ATG TGT GAA GTG AAA ACT GAC TTT 5700Glu Ile Leu Gln Leu Leu Lys Pro Met Cys Glu Val Lys Thr Asp Phe5TGT CAG ACT GTA CTT CCA TAC TTG ATT CAT GAT ATT TTA CTC CAA GAT 5748Cys Gln Thr Val Leu Pro Tyr Leu Ile His Asp Ile Leu Leu Gln Asp0ACA AAT GAA TCA TGG AGA AAT CTG CTT TCT ACA CAT GTT CAG GGA TTT 5796Thr Asn Glu Ser Trp Arg Asn Leu Leu Ser Thr His Val Gln Gly Phe5TTC ACC AGC TGT CTT CGA CAC TTC TCG CAA ACG AGC CGA TCC ACA ACC 5844Phe Thr Ser Cys Leu Arg His Phe Ser Gln Thr Ser Arg Ser Thr Thr01885CCT GCA AAC TTG GAT TCA GAG TCA GAG CAC TTT TTC CGA TGC TGT TTG 5892Pro Ala Asn Leu Asp Ser Glu Ser Glu His Phe Phe Arg Cys Cys Leu0GAT AAA AAA TCA CAA AGA ACA ATG CTT GCT GTT GTG GAC TAC ATG AGA 5940Asp Lys Lys Ser Gln Arg Thr Met Leu Ala Val Val Asp Tyr Met Arg5AGA CAA AAG AGA CCT TCT TCA GGA ACA ATT TTT AAT GAT GCT TTC TGG 5988Arg Gln Lys Arg Pro Ser Ser Gly Thr Ile Phe Asn Asp Ala Phe Trp0CTG GAT TTA AAT TAT CTA GAA GTT GCC AAG GTA GCT CAG TCT TGT GCT 6036Leu Asp Leu Asn Tyr Leu Glu Val Ala Lys Val Ala Gln Ser Cys Ala5GCT CAC TTT ACA GCT TTA CTC TAT GCA GAA ATC TAT GCA GAT AAG AAA 6084Ala His Phe Thr Ala Leu Leu Tyr Ala Glu Ile Tyr Ala Asp Lys Lys01965AGT ATG GAT GAT CAA GAG AAA AGA AGT CTT GCA TTT GAA GAA GGA AGC 6132Ser Met Asp Asp Gln Glu Lys Arg Ser Leu Ala Phe Glu Glu Gly Ser0CAG AGT ACA ACT ATT TCT AGC TTG AGT GAA AAA AGT AAA GAA GAA ACT 6180Gln Ser Thr Thr Ile Ser Ser Leu Ser Glu Lys Ser Lys Glu Glu Thr5GGA ATA AGT TTA CAG GAT CTT CTC TTA GAA ATC TAC AGA AGT ATA GGG 6228Gly Ile Ser Leu Gln Asp Leu Leu Leu Glu Ile Tyr Arg Ser Ile Gly200020052010GAG CCA GAT AGT TTG TAT GGC TGT GGT GGA GGG AAG ATG TTA CAA CCC 6276Glu Pro Asp Ser Leu Tyr Gly Cys Gly Gly Gly Lys Met Leu Gln Pro201520202025ATT ACT AGA CTA CGA ACA TAT GAA CAC GAA GCA ATG TGG GGC AAA GCC 6324Ile Thr Arg Leu Arg Thr Tyr Glu His Glu Ala Met Trp Gly Lys Ala2030203520402045CTA GTA ACA TAT GAC CTC GAA ACA GCA ATC CCC TCA TCA ACA CGC CAG 6372Leu Val Thr Tyr Asp Leu Glu Thr Ala Ile Pro Ser Ser Thr Arg Gln205020552060GCA GGA ATC ATT CAG GCC TTG CAG AAT TTG GGA CTC TGC CAT ATT CTT 6420Ala Gly Ile Ile Gln Ala Leu Gln Asn Leu Gly Leu Cys His Ile Leu206520702075TCC GTC TAT TTA AAA GGA TTG GAT TAT GAA AAT AAA GAC TGG TGT CCT 6468Ser Val Tyr Leu Lys Gly Leu Asp Tyr Glu Asn Lys Asp Trp Cys Pro208020852090GAA CTA GAA GAA CTT CAT TAC CAA GCA GCA TGG AGG AAT ATG CAG TGG 6516Glu Leu Glu Glu Leu His Tyr Gln Ala Ala Trp Arg Asn Met Gln Trp209521002105GAC CAT TGC ACT TCC GTC AGC AAA GAA GTA GAA GGA ACC AGT TAC CAT 6564Asp His Cys Thr Ser Val Ser Lys Glu Val Glu Gly Thr Ser Tyr His22125GAA TCA TTG TAC AAT GCT CTA CAA TCT CTA AGA GAC AGA GAA TTC TCT 6612Glu Ser Leu Tyr Asn Ala Leu Gln Ser Leu Arg Asp Arg Glu Phe Ser2ACA TTT TAT GAA AGT CTC AAA TAT GCC AGA GTA AAA GAA GTG GAA GAG 6660Thr Phe Tyr Glu Ser Leu Lys Tyr Ala Arg Val Lys Glu Val Glu Glu2ATG TGT AAG CGC AGC CTT GAG TCT GTG TAT TCG CTC TAT CCC ACA CTT 6705Met Cys Lys Arg Ser Leu Glu Ser Val Tyr Ser Leu Tyr Pro Thr Leu2AGC AGG TTG CAG GCC ATT GGA GAG CTG GAA AGC ATT GGG GAG CTT TTC 6756Ser Arg Leu Gln Ala Ile Gly Glu Leu Glu Ser Ile Gly Glu Leu Phe2TCA AGA TCA GTC ACA CAT AGA CAA CTC TCT GAA GTA TAT ATT AAG TGG 6804Ser Arg Ser Val Thr His Arg Gln Leu Ser Glu Val Tyr Ile Lys Trp22205CAG AAA CAC TCC CAG CTT CTC AAG GAC AGT GAT TTT AGT TTT CAG GAG 6852Gln Lys His Ser Gln Leu Leu Lys Asp Ser Asp Phe Ser Phe Gln Glu221022152220CCT ATC ATG GCT CTA CGC ACA GTC ATT TTG GAG ATC CTG ATG GAA AAG 6900Pro Ile Met Ala Leu Arg Thr Val Ile Leu Glu Ile Leu Met Glu Lys222522302235GAA ATG GAC AAC TCA CAA AGA GAA TGT ATT AAG GAC ATT CTC ACC AAA 6948Glu Met Asp Asn Ser Gln Arg Glu Cys Ile Lys Asp Ile Leu Thr Lys224022452250CAC CTT GTA GAA CTC TCT ATA CTG GCC AGA ACT TTC AAG AAC ACT CAG 6996His Leu Val Glu Leu Ser Ile Leu Ala Arg Thr Phe Lys Asn Thr Gln225522602265CTC CCT GAA AGG GCA ATA TTT CAA ATT AAA CAG TAC AAT TCA GTT AGC 7044Leu Pro Glu Arg Ala Ile Phe Gln Ile Lys Gln Tyr Asn Ser Val Ser2270227522802285TGT GGA GTC TCT GAG TGG CAG CTG GAA GAA GCA CAA GTA TTC TGG GCA 7092Cys Gly Val Ser Glu Trp Gln Leu Glu Glu Ala Gln Val Phe Trp Ala229022952300AAA AAG GAG CAG AGT CTT GCC CTG AGT ATT CTC AAG CAA ATG ATC AAG 7140Lys Lys Glu Gln Ser Leu Ala Leu Ser Ile Leu Lys Gln Met Ile Lys230523102315AAG TTG GAT GCC AGC TGT GCA GCG AAC AAT CCC AGC CFA AAA CTT ACA 7188Lys Leu Asp Ala Ser Cys Ala Ala Asn Asn Pro Ser Leu Lys Leu Thr232023252330TAC ACA GAA TGT CTG AGG GTT TGT GGC AAC TGG TTA GCA GAA ACG TGC 7236Tyr Thr Glu Cys Leu Arg Val Cys Gly Asn Trp Leu Ala Glu Thr Cys233523402345TTA GAA AAT CCT GCG GTC ATC ATG CAG ACC TAT CTA GAA AAG GCA GTA 7284Leu Glu Asn Pro Ala Val Ile Met Gln Thr Tyr Leu Glu Lys Ala Val2350235523602365GAA GTT GCT GGA AAT TAT GAT GGA GAA AGT AGT GAT GAG CTA AGA AAT 7332Glu Val Ala Gly Asn Tyr Asp Gly Glu Ser Ser Asp Glu Leu Arg Asn237023752380GGA AAA ATG AAG GCA TTT CTC TCA TTA GCC CGG TTT TCA GAT ACT CAA 7380Gly Lys Met Lys Ala Phe Leu Ser Leu Ala Arg Phe Ser Asp Thr Gln238523902395TAC CAA AGA ATT GAA AAC TAC ATG AAA TCA TCG GAA TTT GAA AAC AAG 7428Tyr Gln Arg Ile Glu Asn Tyr Met Lys Ser Ser Glu Phe Glu Asn Lys240024052410CAA GCT CTC CTG AAA AGA GCC AAA GAG GAA GTA GGT CTC CTT AGG GAA 7476Gln Ala Leu Leu Lys Arg Ala Lys Glu Glu Val Gly Leu Leu Arg Glu241524202425CAT AAA ATT CAG ACA AAC AGA TAC ACA GTA AAG GTT CAG CGA GAG CTG 7524His Lys Ile Gln Thr Asn Arg Tyr Thr Val Lys Val Gln Arg Glu Leu2430243524402445GAG TTG GAT GAA TTA GCC CTG CGT GCA CTG AAA GAG GAT CGT AAA CGC 7572Glu Leu Asp Glu Leu Ala Leu Arg Ala Leu Lys Glu Asp Arg Lys Arg245024552460TTC TTA TGT AAA GCA GTT GAA AAT TAT ATC AAC TGC TTA TTA AGT GGA 7620Phe Leu Cys Lys Ala Val Glu Asn Tyr Ile Asn Cys Leu Leu Ser Gly246524702475GAA GAA CAT GAT ATG TGG GTA TTC CGG CTT TGT TCC CTC TGG CTT GAA 7668Glu Glu His Asp Met Trp Val Phe Arg Leu Cys Ser Leu Trp Leu Glu248024852490AAT TCT GGA GTT TCT GAA GTC AAT GGC ATG ATG AAG AGA GAC GGA ATG 7716Asn Ser Gly Val Ser Glu Val Asn Gly Met Met Lys Arg Asp Gly Met249525002505AAG ATT CCA ACA TAT AAA TTT TTG CCT CTT ATG TAC CAA TTG GCT GCT 7764Lys Ile Pro Thr Tyr Lys Phe Leu Pro Leu Met Tyr Gln Leu Ala Ala25525AGA ATG GGG ACC AAG ATG ATG GGA GGC CTA GGA TTT CAT GAA GTC CTC 7812Arg Met Gly Thr Lys Met Met Gly Gly Leu Gly Phe His Glu Val Leu253025352540AAT AAT CTA ATC TCT AGA ATT TCA ATG GAT CAC CCC CAT CAC ACT TTG 7860Asn Asn Leu Ile Ser Arg Ile Ser Met Asp His Pro His His Thr Leu254525502555TTT ATT ATA CTG GCC TTA GCA AAT GCA AAC AGA GAT GAA TTT CTG ACT 7908Phe Ile Ile Leu Ala Leu Ala Asn Ala Asn Arg Asp Glu Phe Leu Thr256025652570AAA CCA GAG GTA GCC AGA AGA AGC AGA ATA ACT AAA AAT GTG CCT AAA 7956Lys Pro Glu Val Ala Arg Arg Ser Arg Ile Thr Lys Asn Val Pro Lys257525802585CAA AGC TCT CAG CTT GAT GAG GAT CGA ACA GAG GCT GCA AAT AGA ATA 8004Gln Ser Ser Gln Leu Asp Glu Asp Arg Thr Glu Ala Ala Asn Arg Ile2590259526002605ATA TGT ACT ATC AGA AGT AGG AGA CCT CAG ATG GTC AGA AGT GTT GAG 8052Ile Cys Thr Ile Arg Ser Arg Arg Pro Gln Met Val Arg Ser Val Glu261026152620GCA CTT TGT GAT GCT TAT ATT ATA TTA GCA AAC TTA GAT GCC ACT CAG 8100Ala Leu Cys Asp Ala Tyr Ile Ile Leu Ala Asn Leu Asp Ala Thr Gln262526302635TGG AAG ACT CAG AGA AAA GGC ATA AAT ATT CCA GCA GAC CAG CCA ATT 8148Trp Lys Thr Gln Arg Lys Gly Ile Asn Ile Pro Ala Asp Gln Pro Ile264026452650ACT AAA CTT AAG AAT TTA GAA GAT GTT GTT GTC CCT ACT ATG GAA ATT 8196Thr Lys Leu Lys Asn Leu Glu Asp Val Val Val Pro Thr Met Glu Ile265526602665AAG GTG GAC CAC ACA GGA GAA TAT GGA AAT CTG GTG ACT ATA CAG TCA 8244Lys Val Asp His Thr Gly Glu Tyr Gly Asn Leu Val Thr Ile Gln Ser2670267526802685TTT AAA GCA GAA TTT CGC TTA GCA GGA GGT GTA AAT TTA CCA AAA ATA 8292Phe Lys Ala Glu Phe Arg Leu Ala Gly Gly Val Asn Leu Pro Lys Ile269026952700ATA GAT TGT GTA GGT TCC GAT GGC AAG GAG AGG AGA CAG CTT GTT AAG 8340Ile Asp Cys Val Gly Ser Asp Gly Lys Glu Arg Arg Gln Leu Val Lys270527102715GGC CGT GAT GAC CTG AGA CAA GAT GCT GTC ATG CAA CAG GTC TTC CAG 8388Gly Arg Asp Asp Leu Arg Gln Asp Ala Val Met Gln Gln Val Phe Gln272027252730ATG TGT AAT ACA TTA CTG CAG AGA AAC ACG GAA ACT AGG AAG AGG AAA 8436Met Cys Asn Thr Leu Leu Gln Arg Asn Thr Glu Thr Arg Lys Arg Lys273527402745TTA ACT ATC TGT ACT TAT AAG GTG GTT CCC CTC TCT CAG CGA AGT GGT 8484Leu Thr Ile Cys Thr Tyr Lys Val Val Pro Leu Ser Gln Arg Ser Gly2750275527602765GTT CTT GAA TGG TGC ACA GGA ACT GTC CCC ATT GGT GAA TTT CTT GTT 8532Val Leu Glu Trp Cys Thr Gly Thr Val Pro Ile Gly Glu Phe Leu Val277027752780AAC AAT GAA GAT GGT GCT CAT AAA AGA TAC AGG CCA AAT GAT TTC AGT 8580Asn Asn Glu Asp Gly Ala His Lys Arg Tyr Arg Pro Asn Asp Phe Ser278527902795GCC TTT CAG TGC CAA AAG AAA ATG ATG GAG GTG CAA AAA AAG TCT TTT 8628Ala Phe Gln Cys Gln Lys Lys Met Met Glu Val Gln Lys Lys Ser Phe280028052810GAA GAG AAA TAT GAA GTC TTC ATG GAT GTT TGC CAA AAT TTT CAA CCA 8676Glu Glu Lys Tyr Glu Val Phe Met Asp Val Cys Gln Asn Phe Gln Pro281528202825GTT TTC CGT TAC TTC TGC ATG GAA AAA TTC TTG GAT CCA GCT ATT TGG 8724Val Phe Arg Tyr Phe Cys Met Glu Lys Phe Leu Asp Pro Ala Ile Trp2830283528402845TTT GAG AAG CGA TTG GCT TAT ACG CGC AGT GTA GCT ACT TCT TCT ATT 8772Phe Glu Lys Arg Leu Ala Tyr Thr Arg Ser Val Ala Thr Ser Ser Ile285028552860GTT GGT TAC ATA CTT GGA CTT GGT GAT AGA CAT GTA CAG AAT ATC TTG 8820Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Val Gln Asn Ile Leu286528702875ATA AAT GAG CAG TCA GCA GAA CTT GTA CAT ATA GAT CTA GGT GTT GCT 8868Ile Asn Glu Gln Ser Ala Glu Leu Val His Ile Asp Leu Gly Val Ala288028852890TTT GAA CAG GGC AAA ATC CTT CCT ACT CCT GAG ACA GTT CCT TTT AGA 8916Phe Glu Gln Gly Lys Ile Leu Pro Thr Pro Glu Thr Val Pro Phe Arg289529002905CTC ACC AGA GAT ATT GTG GAT GGC ATG GGC ATT ACG GGT GTT GAA GGT 8964Leu Thr Arg Asp Ile Val Asp Gly Met Gly Ile Thr Gly Val Glu Gly29925GTC TTC AGA AGA TGC TGT GAG AAA ACC ATG GAA GTG ATG AGA AAC TCT 9012Val Phe Arg Arg Cys Cys Glu Lys Thr Met Glu Val Met Arg Asn Ser293029352940CAG GAA ACT CTG TTA ACC ATT GTA GAG GTC CTT CTA TAT GAT CCA CTC 9060Gln Glu Thr Leu Leu Thr Ile Val Glu Val Leu Leu Tyr Asp Pro Leu294529502955TTT GAC TGG ACC ATG AAT CCT TTG AAA GCT TTG TAT TTA CAG CAG AGG 9108Phe Asp Trp Thr Met Asn Pro Leu Lys Ala Leu Tyr Leu Gln Gln Arg296029652970CCG GAA GAT GAA ACT GAG CTT CAC CCT ACT CTG AAT GCA GAT GAC CAA 9156Pro Glu Asp Glu Thr Glu Leu His Pro Thr Leu Asn Ala Asp Asp Gln297529802985GAA TGC AAA CGA AAT CTC AGT GAT ATT GAC CAG AGT TTC GAC AAA GTA 9204Glu Cys Lys Arg Asn Leu Ser Asp Ile Asp Gln Sar Phe Asp Lys Val2990299530003005GCT GAA CGT GTC TTA ATG AGA CTA CAA GAG AAA CTG AAA GGA GTG GAA 9252Ala Glu Arg Val Leu Met Arg Leu Gln Glu Lys Leu Lys Gly Val Glu301030153020GAA GGC ACT GTG CTC AGT GTT GGT GGA CAG GTG AAT TTG CTC ATA CAG 9300Glu Gly Thr Val Leu Ser Val Gly Gly Gln Val Asn Leu Leu Ile Gln302530303035CAG GCC ATA GAC CCC AAA AAT CTC AGC CGA CTT TTC CCA GGA TGG AAA 9348Gln Ala Ile Asp Pro Lys Asn Leu Ser Arg Leu Phe Pro Gly Trp Lys304030453050GCT TGG GTG TGATCTTCAG TATATGAATT ACCCTTTC 9385Ala Trp Val3055(2)SEQ ID NO35的說明(i)序列特征(A)長度3056個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型蛋白(xi)序列描述SEQ ID NO35Met Ser Leu Val Leu Asn Asp Leu Leu Ile Cys Cys Arg Gln Leu Glu1 5 10 15His Asp Arg Ala Thr Glu Arg Lys Lys Glu Val Glu Lys Phe Lys Arg20 25 30Leu Ile Arg Asp Pro Glu Thr Ile Lys His Leu Asp Arg His Ser Asp35 40 45Ser Lys Gln Gly Lys Tyr Leu Asn Trp Asp Ala Val Phe Arg Phe Leu50 55 60Gln Lys Tyr Ile Gln Lys Glu Thr Glu Cys Leu Arg Ile Ala Lys Pro65 70 75 80Asn Val Ser Ala Ser Thr Gln Ala Ser Arg Gln Lys Lys Met Gln Glu85 90 95Ile Ser Ser Leu Val Lys Tyr Phe Ile Lys Cys Ala Asn Arg Arg Ala100 105 110Pro Arg Leu Lys Cys Gln Glu Leu Leu Asn Tyr Ile Met Asp Thr Val115 120 125Lys Asp Ser Ser Asn Gly Ala Ile Tyr Gly Ala Asp Cys Ser Asn Ile130 135 140Leu Leu Lys Asp Ile Leu Ser Val Arg Lys Tyr Trp Cys Glu Ile Ser145 150 155 160Gln Gln Gln Trp Leu Glu Leu Phe Ser Val Tyr Phe Arg Leu Tyr Leu165 170 175Lys Pro Ser Gln Asp Val His Arg Val Leu Val Ala Arg Ile Ile His180 185 190Ala Val Thr Lys Gly Cys Cys Ser Gln Thr Asp Gly Leu Asn Ser Lys195 200 205Phe Leu Asp Phe Phe Ser Lys Ala Ile Gln Cys Ala Arg Gln Glu Lys210 215 220Ser Ser Ser Gly Leu Asn His Ile Leu Ala Ala Leu Thr Ile Phe Leu225 230 235 240Lys Thr Leu Ala Val Asn Phe Arg Ile Arg Val Cys Glu Leu Gly Asp245 250 255Glu Ile Leu Pro Thr Leu Leu Tyr Ile Trp Thr Gln His Arg Leu Asn260 265 270Asp Ser Leu Lys Glu Val Ile Ile Glu Leu Phe Gln Leu Gln Ile Tyr275 280 285Ile His His Pro Lys Gly Ala Lys Thr Gln Glu Lys Gly Ala Tyr Glu290 295 300Ser Thr Lys Trp Arg Ser Ile Leu Tyr Asn Leu Tyr Asp Leu Leu Val305 310 315 320Asn Glu Ile Ser His Ile Gly Ser Arg Gly Lys Tyr Ser Ser Gly Phe325 330 335Arg Asn Ile Ala Val Lys Glu Asn Leu Ile Glu Leu Met Ala Asp Ile340 345 350Cys His Gln Val Phe Asn Glu Asp Thr Arg Ser Leu Glu Ile Ser Gln355 360 365Ser Tyr Thr Thr Thr Gln Arg Glu Ser Ser Asp Tyr Ser Val Pro Cys370 375 380Lys Arg Lys Lys Ile Glu Leu Gly Trp Glu Val Ile Lys Asp His Leu385 390 395 400Gln Lys Ser Gln Asn Asp Phe Asp Leu Val Pro Trp Leu Gln Ile Ala405 410 415Thr Gln Leu Ile Ser Lys Tyr Pro Ala Ser Leu Pro Asn Cys Glu Leu420 425 430Ser Pro Leu Leu Met Ile Leu Ser Gln Leu Leu Pro Gln Gln Arg His435 440 445Gly Glu Arg Thr Pro Tyr Val Leu Arg Cys Leu Thr Glu Val Ala Leu450 455 460Cys Gln Asp Lys Arg Ser Asn Leu Glu Ser Ser Gln Lys Ser Asp Leu465 470 475 480Leu Lys Leu Trp Asn Lys Ile Trp Cys Ile Thr Phe Arg Gly Ile Ser485 490 495Ser Glu Gln Ile Gln Ala Glu Asn Phe Gly Leu Leu Gly Ala Ile Ile500 505 510Gln Gly Ser Leu Val Glu Val Asp Arg Glu Phe Trp Lys Leu Phe Thr515 520 525Gly Ser Ala Cys Arg Pro Ser Cys Pro Ala Val Cys Cys Leu Thr Leu530 535 540Ala Leu Thr Thr Ser Ile Val Pro Gly Ala Val Lys Met Gly Ile Glu545 550 555 560Gln Asn Met Cys Glu Val Asn Arg Ser Phe Ser Leu Lys Glu Ser Ile565 570 575Met Lys Trp Leu Leu Phe Tyr Gln Leu Glu Gly Asp Leu Glu Asn Ser580 585 590Thr Glu Val Pro Pro Ile Leu His Ser Asn Phe Pro His Leu Val Leu595 600 605Glu Lys Ile Leu Val Ser Leu Thr Met Lys Asn Cys Lys Ala Ala Met610 615 620Asn Phe Phe Gln Ser Val Pro Glu Cys Glu His His Gln Lys Asp Lys625 630 635 640Glu Glu Leu Ser Phe Ser Glu Val Glu Glu Leu Phe Leu Gln Thr Thr645 650 655Phe Asp Lys Met Asp Phe Leu Thr Ile Val Arg Glu Cys Gly Ile Glu660 665 670Lys His Gln Ser Ser Ile Gly Phe Ser Val His Gln Asn Leu Lys Glu675 680 685Ser Leu Asp Arg Cys Leu Leu Gly Leu Ser Glu Gln Leu Leu Asn Asn690 695 700Tyr Ser Ser Glu Ile Thr Asn Ser Glu Thr Leu Val Arg Cys Ser Arg705 710 715 720Leu Leu Val Gly Val Leu Gly Cys Tyr Cys Tyr Met Gly Val Ile Ala725 730 735Glu Glu Glu Ala Tyr Lys Ser Glu Leu Phe Gln Lys Ala Asn Ser Leu740 745 750Met Gln Cys Ala Gly Glu Ser Ile Thr Leu Phe Lys Asn Lys Thr Asn755 760 765Glu Glu Phe Arg Ile Gly Ser Leu Arg Asn Met Met Gln Leu Cys Thr770 775 780Arg Cys Leu Ser Asn Cys Thr Lys Lys Ser Pro Asn Lys Ile Ala Ser785 790 795 800Gly Phe Phe Leu Arg Leu Leu Thr Ser Lys Leu Met Asn Asp Ile Ala805 810 815Asp Ile Cys Lys Ser Leu Ala Ser Phe Ile Lys Lys Pro Phe Asp Arg820 825 830Gly Glu Val Glu Ser Met Glu Asp Asp Thr Asn Gly Asn Leu Met Glu835 840 845Val Glu Asp Gln Ser Ser Met Asn Leu Phe Asn Asp Tyr Pro Asp Ser850 855 860Ser Val Ser Asp Ala Asn Glu Pro Gly Glu Ser Gln Ser Thr Ile Gly865 870 875 880Ala Ile Asn Pro Leu Ala Glu Glu Tyr Leu Ser Lys Gln Asp Leu Leu885 890 895Phe Leu Asp Met Leu Lys Phe Leu Cys Leu Cys Val Thr Thr Ala Gln900 905 910Thr Asn Thr Val Ser Phe Arg Ala Ala Asp Ile Arg Arg Lys Leu Leu915 920 925Met Leu Ile Asp Ser Ser Thr Leu Glu Pro Thr Lys Ser Leu His Leu930 935 940His Met Tyr Leu Met Leu Leu Lys Glu Leu Pro Gly Glu Glu Tyr Pro945 950 955 960Leu Pro Met Glu Asp Val Leu Glu Leu Leu Lys Pro Leu Ser Asn Val965 970 975Cys Ser Leu Tyr Arg Arg Asp Gln Asp Val Cys Lys Thr Ile Leu Asn980 985 990His Val Leu His Val Val Lys Asn Leu Gly Gln Ser Asn Met Asp Ser995 10001005Glu Asn Thr Arg Asp Ala Gln Gly Gln Phe Leu Thr Val Ile Gly Ala0Phe Trp His Leu Thr Lys Glu Arg Lys Tyr Ile Phe Ser Val Arg Met51040Ala Leu Val Asn Cys Leu Lys Thr Leu Leu Glu Ala Asp Pro Tyr Ser5Lys Trp Ala Ile Leu Asn Val Met Gly Lys Asp Phe Pro Val Asn Glu0Val Phe Thr Gln Phe Leu Ala Asp Asn His His Gln Val Arg Met Leu5Ala Ala Glu Ser Ile Asn Arg Leu Phe Gln Asp Thr Lys Gly Asp Ser0Ser Arg Leu Leu Lys Ala Leu Pro Leu Lys Leu Gln Gln Thr Ala Phe51120Glu Asn Ala Tyr Leu Lys Ala Gln Glu Gly Met Arg Glu Met Ser His5Ser Ala Glu Asn Pro Glu Thr Leu Asp Glu Ile Tyr Asn Arg Lys Ser0Val Leu Leu Thr Leu Ile Ala Val Val Leu Ser Cys Ser Pro Ile Cys5Glu Lys Gln Ala Leu Phe Ala Leu Cys Lys Ser Val Lys Glu Asn Gly0Leu Glu Pro His Leu Val Lys Lys Val Leu Glu Lys Val Ser Glu Thr51200Phe Gly Tyr Arg Arg Leu Glu Asp Phe Met Ala Ser His Leu Asp Tyr5Leu Val Leu Glu Trp Leu Asn Leu Gln Asp Thr Glu Tyr Asn Leu Ser0Ser Phe Pro Phe Ile Leu Leu Asn Tyr Thr Asn Ile Glu Asp Phe Tyr5Arg Ser Cys Tyr Lys Val Leu Ile Pro His Leu Val Ile Arg Ser His0Phe Asp Glu Val Lys Ser Ile Ala Asn Gln Ile Gln Glu Asp Trp Lys51280Ser Leu Leu Thr Asp Cys Phe Pro Lys Ile Leu Val Asn Ile Leu Pro5Tyr Phe Ala Tyr Glu Gly Thr Arg Asp Ser Gly Met Ala Gln Gln Arg0Glu Thr Ala Thr Lys Val Tyr Asp Met Leu Lys Ser Glu Asn Leu Leu5Gly Lys Gln Ile Asp His Leu Phe Ile Ser Asn Leu Pro Glu Ile Val0Val Glu Leu Leu Met Thr Leu His Glu Pro Ala Asn Ser Ser Ala Ser51360Gln Ser Thr Asp Leu Cys Asp Phe Ser Gly Asp Leu Asp Pro Ala Pro5Asn Pro Pro His Phe Pro Ser His Val Ile Lys Ala Thr Phe Ala Tyr0Ile Ser Asn Cys His Lys Thr Lys Leu Lys Ser Ile Leu Glu Ile Leu5Ser Lys Ser Pro Asp Ser Tyr Gln Lys Ile Leu Leu Ala Ile Cys Glu0Gln Ala Ala Glu Thr Asn Asn Val Tyr Lys Lys His Arg Ile Leu Lys51440Ile Tyr His Leu Phe Val Ser Leu Leu Leu Lys Asp Ile Lys Ser Gly5Leu Gly Gly Ala Trp Ala Phe Val Leu Arg Asp Val Ile Tyr Thr Leu0Ile His Tyr Ile Asn Gln Arg Pro Ser Cys Ile Met Asp Val Ser Leu5Arg Ser Phe Ser Leu Cys Cys Asp Leu Leu Ser Gln Val Cys Gln Thr0Ala Val Thr Tyr Cys Lys Asp Ala Leu Glu Asn His Leu His Val Ile51520Val Gly Thr Leu Ile Pro Leu Val Tyr Glu Gln Val Glu Val Gln Lys5Gln Val Leu Asp Leu Leu Lys Tyr Leu Val Ile Asp Asn Lys Asp Asn0Glu Asn Leu Tyr Ile Thr Ile Lys Leu Leu Asp Pro Phe Pro Asp His5Val Val Phe Lys Asp Leu Arg Ile Thr Gln Gln Lys Ile Lys Tyr Ser0Arg Gly Pro Phe Ser Leu Leu Glu Glu Ile Asn His Phe Leu Ser Val51600Ser Val Tyr Asp Ala Leu Pro Leu Thr Arg Leu Glu Gly Leu Lys Asp5Leu Arg Arg Gln Leu Glu Leu His Lys Asp Gln Met Val Asp Ile Met0Arg Ala Ser Gln Asp Asn Pro Gln Asp Gly Ile Met Val Lys Leu Val5Val Asn Leu Leu Gln Leu Ser Lys Met Ala Ile Asn His Thr Gly Glu0Lys Glu Val Leu Glu Ala Val Gly Ser Cys Leu Gly Glu Val Gly Pro51680Ile Asp Phe Ser Thr Ile Ala Ile Gln His Ser Lys Asp Ala Ser Tyr5Thr Lys Ala Leu Lys Leu Phe Glu Asp Lys Glu Leu Gln Trp Thr Phe0Ile Met Leu Thr Tyr Leu Asn Asn Thr Leu Val Glu Asp Cys Val Lys5Val Arg Ser Ala Ala Val Thr Cys Leu Lys Asn Ile Leu Ala Thr Lys0Thr Gly His Ser Phe Trp Glu Ile Tyr Lys Met Thr Thr Asp Pro Met51760Leu Ala Tyr Leu Gln Pro Phe Arg Thr Ser Arg Lys Lys Phe Leu Glu5Val Pro Arg Phe Asp Lys Glu Asn Pro Phe Glu Gly Leu Asp Asp Ile0Asn Leu Trp Ile Pro Leu Ser Glu Asn His Asp Ile Trp Ile Lys Thr5Leu Thr Cys Ala Phe Leu Asp Ser Gly Gly Thr Lys Cys Glu Ile Leu0Gln Leu Leu Lys Pro Met Cys Glu Val Lys Thr Asp Phe Cys Gln Thr51840Val Leu Pro Tyr Leu Ile His Asp Ile Leu Leu Gln Asp Thr Asn Glu5Ser Trp Arg Asn Leu Leu Ser Thr His Val Gln Gly Phe Phe Thr Ser0Cys Leu Arg His Phe Ser Gln Thr Ser Arg Ser Thr Thr Pro Ala Asn5Leu Asp Ser Glu Ser Glu His Phe Phe Arg Cys Cys Leu Asp Lys Lys0Ser Gln Arg Thr Met Leu Ala Val Val Asp Tyr Met Arg Arg Gln Lys51920Arg Pro Ser Ser Gly Thr Ile Phe Asn Asp Ala Phe Trp Leu Asp Leu5Asn Tyr Leu Glu Val Ala Lys Val Ala Gln Ser Cys Ala Ala His Phe0Thr Ala Leu Leu Tyr Ala Glu Ile Tyr Ala Asp Lys Lys Ser Met Asp5Asp Gln Glu Lys Arg Ser Leu Ala Phe Glu Glu Gly Ser Gln Ser Thr0Thr Ile Ser Ser Leu Ser Glu Lys Ser Lys Glu Glu Thr Gly Ile Ser52000Leu Gln Asp Leu Leu Leu Glu Ile Tyr Arg Ser Ile Gly Glu Pro Asp200520102015Ser Leu Tyr Gly Cys Gly Gly Gly Lys Met Leu Gln Pro Ile Thr Arg202020252030Leu Arg Thr Tyr Glu His Glu Ala Met Trp Gly Lys Ala Leu Val Thr203520402045Tyr Asp Leu Glu Thr Ala Ile Pro Ser Ser Thr Arg Gln Ala Gly Ile205020552060Ile Gln Ala Leu Gln Asn Leu Gly Leu Cys His Ile Leu Ser Val Tyr2065207020752080Leu Lys Gly Leu Asp Tyr Glu Asn Lys Asp Trp Cys Pro Glu Leu Glu208520902095Glu Leu His Tyr Gln Ala Ala Trp Arg Asn Met Gln Trp Asp His Cys2Thr Ser Val Ser Lys Glu Val Glu Gly Thr Ser Tyr His Glu Ser Leu2Tyr Asn Ala Leu Gln Ser Leu Arg Asp Arg Glu Phe Ser Thr Phe Tyr2Glu Ser Leu Lys Tyr Ala Arg Val Lys Glu Val Glu Glu Met Cys Lys22160Arg Ser Leu Glu Ser Val Tyr Ser Leu Tyr Pro Thr Leu Ser Arg Leu2Gln Ala Ile Gly Glu Leu Glu Ser Ile Gly Glu Leu Phe Ser Arg Ser2Val Thr His Arg Gln Leu Ser Glu Val Tyr Ile Lys Trp Gln Lys His2Ser Gln Leu Leu Lys Asp Ser Asp Phe Ser Phe Gln Glu Pro Ile Met221022152220Ala Leu Arg Thr Val Ile Leu Glu Ile Leu Met Glu Lys Glu Met Asp2225223022352240Asn Ser Gln Arg Glu Cys Ile Lys Asp Ile Leu Thr Lys His Leu Val224522502255Glu Leu Ser Ile Leu Ala Arg Thr Phe Lys Asn Thr Gln Leu Pro Glu226022652270Arg Ala Ile Phe Gln Ile Lys Gln Tyr Asn Ser Val Ser Cys Gly Val227522802285Ser Glu Trp Gln Leu Glu Glu Ala Gln Val Phe Trp Ala Lys Lys Glu229022952300Gln Ser Leu Ala Leu Ser Ile Leu Lys Gln Met Ile Lys Lys Leu Asp2305231023152320Ala Ser Cys Ala Ala Asn Asn Pro Ser Leu Lys Leu Thr Tyr Thr Glu232523302335Cys Leu Arg Val Cys Gly Asn Trp Leu Ala Glu Thr Cys Leu Glu Asn234023452350Pro Ala Val Ile Met Gln Thr Tyr Leu Glu Lys Ala Val Glu Val Ala235523602365Gly Asn Tyr Asp Gly Glu Ser Ser Asp Glu Leu Arg Asn Gly Lys Met237023752380Lys Ala Phe Leu Ser Leu Ala Arg Phe Ser Asp Thr Gln Tyr Gln Arg2385239023952400Ile Glu Asn Tyr Met Lys Ser Ser Glu Phe Glu Asn Lys Gln Ala Leu240524102415Leu Lys Arg Ala Lys Glu Glu Val Gly Leu Leu Arg Glu His Lys Ile242024252430Gln Thr Asn Arg Tyr Thr Val Lys Val Gln Arg Glu Leu Glu Leu Asp243524402445Glu Leu Ala Leu Arg Ala Leu Lys Glu Asp Arg lys Arg Phe Leu Cys245024552460Lys Ala Val Glu Asn Tyr Ile Asn Cys Leu Leu Ser Gly Glu Glu His2465247024752480Asp Met Trp Val Phe Arg Leu Cys Ser Leu Trp Leu Glu Asn Ser Gly248524902495Val Ser Glu Val Asn Gly Met Met Lys Arg Asp Gly Met Lys Ile Pro250025052510Thr Tyr Lys Phe Leu Pro Leu Met Tyr Gln Leu Ala Ala Arg Met Gly251525202525Thr Lys Met Met Gly Gly Leu Gly Phe His Glu Val Leu Asn Asn Leu253025352540Ile Ser Arg Ile Ser Met Asp His Pro His His Thr Leu Phe Ile Ile2545255025552560Leu Ala Leu Ala Asn Ala Asn Arg Asp Glu Phe Leu Thr Lys Pro Glu256525702575Val Ala Arg Arg Ser Arg Ile Thr Lys Asn Val Pro Lys Gln Ser Ser258025852590Gln Leu Asp Glu Asp Arg Thr Glu Ala Ala Asn Arg Ile Ile Cys Thr259526002605Ile Arg Ser Arg Arg Pro Gln Met Val Arg Ser Val Glu Ala Leu Cys261026152620Asp Ala Tyr Ile Ile Leu Ala Asn Leu Asp Ala Thr Gln Trp Lys Thr2625263026352640Gln Arg Lys Gly Ile Asn Ile Pro Ala Asp Gln Pro Ile Thr Lys Leu264526502655Lys Asn Leu Glu Asp Val Val Val Pro Thr Met Glu Ile Lys Val Asp266026652670His Thr Gly Glu Tyr Gly Asn Leu Val Thr Ile Gln Ser Phe Lys Ala267526802685Glu Phe Arg Leu Ala Gly Gly Val Asn Leu Pro Lys Ile Ile Asp Cys269026952700Val Gly Ser Asp Gly Lys Glu Arg Arg Gln Leu Val Lys Gly Arg Asp2705271027152720Asp Leu Arg Gln Asp Ala Val Met Gln Gln Val Phe Gln Met Cys Asn272527302735Thr Leu Leu Gln Arg Asn Thr Glu Thr Arg Lys Arg Lys Leu Thr Ile274027452750Cys Thr Tyr Lys Val Val Pro Leu Ser Gln Arg Ser Gly Val Leu Glu275527602765Trp Cys Thr Gly Thr Val Pro Ile Gly Glu Phe Leu Val Asn Asn Glu277027752780Asp Gly Ala His Lys Arg Tyr Arg Pro Asn Asp Phe Ser Ala Phe Gln2785279027952800Cys Gln Lys Lys Met Met Glu Val Gln Lys Lys Ser Phe Glu Glu Lys280528102815Tyr Glu Val Phe Met Asp Val Cys Gln Asn Phe Gln Pro Val Phe Arg282028252830Tyr Phe Cys Met Glu Lys Phe Leu Asp Pro Ala Ile Trp Phe Glu Lys283528402845Arg Leu Ala Tyr Thr Arg Ser Val Ala Thr Ser Ser Ile Val Gly Tyr285028552860Ile Leu Gly Leu Gly Asp Arg His Val Gln Asn Ile Leu Ile Asn Glu2865287028752880Gln Ser Ala Glu Leu Val His Ile Asp Leu Gly Val Ala Phe Glu Gln288528902895Gly Lys Ile Leu Pro Thr Pro Glu Thr Val Pro Phe Arg Leu Thr Arg290029052910Asp Ile Val Asp Gly Met Gly Ile Thr Gly Val Glu Gly Val Phe Arg291529202925Arg Cys Cys Glu Lys Thr Met Glu Val Met Arg Asn Ser Gln Glu Thr293029352940Leu Leu Thr Ile Val Glu Val Leu Leu Tyr Asp Pro Leu Phe Asp Trp2945295029552960Thr Met Asn Pro Leu Lys Ala Leu Tyr Leu Gln Gln Arg Pro Glu Asp296529702975Glu Thr Glu Leu His Pro Thr Leu Asn Ala Asp Asp Gln Glu Cys Lys298029852990Arg Asn Leu Ser Asp Ile Asp Gln Ser Phe Asp Lys Val Ala Glu Arg299530003005Val Leu Met Arg Leu Gln Glu Lys Leu Lys Gly Val Glu Glu Gly Thr301030153020Val Leu Ser Val Gly Gly Gin Val Asn Leu Leu Ile Gln Gln Ala Ile3025303030353040Asp Pro Lys Asn Leu Ser Arg Leu Phe Pro Gly Trp Lys Ala Trp Val304530503055(2)SEQ ID NO36的說明(i)序列特征(A)長度19個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型肽(xi)序列描述SEQ ID NO36Met Ser Gly Gly Ser Ser Cys Gln Thr Pro Ser Arg Ala Ile Pro Ala1 5 10 15Thr Arg Arg(2)SEQ ID NO37的說明(i)序列特征(A)長度21個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型肽(xi)序列描述SEQ ID NO37Gly Asp Tyr Ser Thr Thr Pro Gly Gly Thr Leu Phe Ser Thr Thr Pro1 5 10 15Gly Gly Thr Arg Arg20(2)SEQ ID NO38的說明(i)序列特征(A)長度12個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型肽(xi)序列描述SEQ ID NO38Glu Cys Arg Asn Ser Pro Val Thr Lys Thr Arg Arg1 5 10(2)SEQ ID NO39的說明(i)序列特征(A)長度12個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型肽(xi)序列描述SEQ ID NO39Gly Val Thr Ser Pro Ser Ser Asp Glu Pro Arg Arg1 5 10(2)SEQ ID NO40的說明(i)序列特征(A)長度10個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型肽(xi)序列描述SEQ ID NO40Met Glu Ala Ser Gln Ser His Leu Arg Arg1 5 10(2)SEQ ID NO41的說明(i)序列特征(A)長度12個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型肽(xi)序列描述SEQ ID NO41Arg Arg Asn Ser Pro Glu Asp Lys Arg Ala Gly Gly1 5 10(2)SEQ ID NO42的說明(i)序列特征(A)長度12個氨基酸(B)類型氨基酸(D)拓撲結構線性(ii)分子類型肽(xi)序列描述SEQ ID NO42Gly Glu Glu Ser Gln Phe Glu Met Asp Ile Arg Arg1 5 10
權利要求
1.包含編碼SEQ ID NO31列出的PIK-相關激酶MCCS1α氨基酸序列的多核苷酸的純化并分離的多核苷酸。
2.包含編碼SEQ ID NO33列出的PIK-相關激酶MCCS1β氨基酸序列的多核苷酸的純化并分離的多核苷酸。
3.權利要求1或2的多核苷酸，它為DNA。
4.權利要求3的DNA，它為cDNA。
5.由SEQ ID NO30列出的DNA序列組成的MCCS1αcDNA。
6.由SEQ ID NO32列出的DNA序列組成的MCCS1βDNA。
7.權利要求3的DNA，它為基因組DNA。
8.權利要求3的DNA的RNA轉錄物。
9.權利要求3的DNA，它為全部或部分化學合成的DNA。
10.一種DNA，它包含選自編碼全長哺乳動物MCCS1激酶的DNAa)在嚴格條件下與SEQ ID NO30 DNA的非編碼鏈雜交的DNA；b)在嚴格條件下與SEQ ID NO3 DNA的非編碼鏈雜交的DNA；和c)在嚴格條件下與SEQ ID NO32 DNA的非編碼鏈雜交的DNA。
11.包含權利要求3或10的DNA的載體。
12.權利要求11的載體，其中所述DNA被可行地連接到一個表達控制DNA序列上。
13.以允許MCCS1激酶在所述宿主細胞中表達的方式，用權利要求3或10的DNA穩定轉化或轉染的宿主細胞。
14.產生PIK相關激酶MCCS1的方法，此方法包含在適當的營養培養基中生長權利要求11的宿主細胞并從所述細胞或其生長的培養基中分離MCCS1激酶。
15.包含由SEQ ID NO31組成的PIK相關激酶MCCS1α氨基酸序列的純化分離多肽。
16.包含由SEQ ID NO33組成的PIK相關激酶MCCS1α氨基酸序列的純化分離多肽。
17.能特異地與PIK相關激酶MCCS1結合的多肽或肽。
18.權利要求17的抗體產物。
19.權利要求18的單克隆抗體。
20.產生權利要求19單克隆抗體的雜交瘤細胞系。
21.鑒定MCCS1激酶活性調制劑的方法，它包含步驟a)有或無被試化合物存在下，在激酶緩沖液中將MCCS1激酶樣品與γ-32P-ATP和外源性激酶底物一起溫育，并b)測量轉移到所述底物的磷酸鹽摩爾數；其中存在被試化合物情況下轉移到所述底物的32P-磷酸鹽摩爾數比不存在被試化合物情況下轉移到所述底物的32P-磷酸鹽摩爾數增加表示所述被試化合物是所述MCCS1激酶的激活劑，其中存在被試化合物情況下轉移到所述底物的32P-磷酸鹽摩爾數比不存在被試化合物情況下轉移到所述底物的32P-磷酸鹽摩爾數減少表示所述被試化合物是所述MCCS1激酶的抑制劑。
22.雜交瘤細胞系224C。
23.雜交瘤細胞系224F。
24.鑒定抑制MCCS1的化合物的方法，它包含步驟a)在基因改變的細胞中表達MCCS1，從而降低細胞對DNA損傷的敏感性，所述的敏感性與基因改變相關；b)在有或無被試調制劑化合物存在下，將步驟(a)的基因改變細胞經DNA損傷處理；c)測量細胞對DNA損傷的敏感性；并d)鑒定作為MCCS1活性的抑制劑、恢復細胞對DNA損傷敏感性的被試化合物。
25.鑒定抑制ATM的化合物的方法，它包含步驟a)在基因改變的細胞中表達ATM，從而降低細胞對DNA損傷的敏感性，所述的敏感性與基因改變有關；b)有或無被試調制劑化合物存在下，將步驟(a)的基因改變細胞經DNA損傷處理；c)測量細胞對DNA損傷的敏感性；并d)鑒定作為ATM活性抑制劑、恢復細胞對DNA損傷敏感性的被試化合物。
26.鑒定ATM激酶活性調制劑的方法，它包含步驟a)有或無被試化合物存在下，在激酶緩沖液中將ATM激酶樣品與γ-32P-ATP和外源性激酶底物一起溫育，并b)測量轉移到所述底物的磷酸鹽摩爾數；其中存在被試化合物情況下轉移到所述底物的32P-磷酸鹽摩爾數比不存在被試化合物情況下轉移到所述底物的32P-磷酸鹽摩爾數增加表示所述被試化合物是所述ATM激酶的激活劑，存在被試化合物情況下轉移到所述底物的32P-磷酸鹽摩爾數比不存在被試化合物情況下轉移到所述底物的32P-磷酸鹽摩爾數減少表示所述被試化合物是所述ATM激酶的抑制劑。
全文摘要
本發明廣泛涉及編碼細胞中對DNA損傷反應所必要的、細胞周期關卡磷脂酰肌醇激酶(PIK)相關蛋白的基因。這些PIK相關激酶在DMA損傷后停滯細胞周期以在有絲分裂或DNA復制起始之前使DNA修復的調節通路中是需要的。更特別地,本發明提供一種新的人細胞周期關卡PIK相關激酶MCCS1和編碼MCCS1的多核苷酸序列。本發明還提供了鑒別如作為化療和放射佐劑有用的MCCS1調制劑的方法。而且,提供了鑒別細胞周期關卡磷脂酰肌醇激酶(PIK)－相關蛋白、定為ATM的調制劑的方法。
文檔編號C12N9/12GK1199420SQ96192586
公開日1998年11月18日 申請日期1996年11月18日 優先權日1995年11月16日
發明者M·F·霍艾克斯特拉, D·A·霍爾茨曼, K·S·基加恩 申請人:艾科斯有限公司