專利名稱：除蟲菌素糖苷配基合成酶基因的制作方法
技術(shù)領(lǐng)域：
本發(fā)明涉及編碼參與除蟲菌素化合物(它是一種聚酮化合物)的生物合成的多功能酶的DNA；由所述DNA所編碼的多肽；含有所述DNA的載體；用所述DNA或載體轉(zhuǎn)化過的宿主細(xì)胞；和用于生產(chǎn)除蟲菌素的方法。
背景技術(shù)：
聚酮化合物是含有多種天然物質(zhì)的一類化合物，所述天然物質(zhì)的結(jié)構(gòu)和功能不同。已知聚酮化合物包括具有多種生物學(xué)活性的化合物，如抗細(xì)菌劑、抗真菌劑、抗寄生蟲劑、抗昆蟲劑、抗腫瘤劑和免疫抑制劑、以及通過細(xì)菌、真菌和植物所生產(chǎn)的芳香化合物。
上述各種聚酮化合物是通過相同的生物合成機(jī)制合成的，該機(jī)制與脂肪酸的生物合成十分相似。就是說，聚酮化合物是通過以下步驟生物合成的連續(xù)縮合包括乙酸和丙酸在內(nèi)的低級(jí)脂肪酸，而隨后的反應(yīng)，如酮的還原、脫水和在延伸的?；鶊F(tuán)的β位置上的每一個(gè)羰基基團(tuán)的烯酰還原，類似于脂肪酸合成。多種聚酮化合物的各種重復(fù)的合成過程是由一種大分子、多功能酶復(fù)合體催化的，它具有每一種催化活性所需要的特殊活性部位(功能域)。例如，聚酮化合物生物合成的一般反應(yīng)方式披露于以下文獻(xiàn)中遺傳學(xué)年度綜述24，37(1990)，和微生物學(xué)年度綜述47，875(1993)。
業(yè)已證實(shí)，編碼聚酮化合物合成酶的DNA序列通常編碼聚酮化合物主鏈合成的所有必需的活性。所述編碼聚酮化合物合成酶的DNA序列由一些組件組成，即參與縮合步驟和縮合之后的修飾步驟的重復(fù)單元。每一種催化活性與每一個(gè)縮合步驟的特定羧酸成分的專一性有關(guān)，或與一個(gè)不同位點(diǎn)有關(guān)，該位點(diǎn)決定在特定縮合步驟之后所要獲得的修飾功能。例如，國際申請(qǐng)?zhí)朩O93/13663披露了編碼紅色糖多孢菌的聚酮化合物合成酶的基因的組成。該基因包括6個(gè)組件，每一個(gè)組件負(fù)責(zé)一個(gè)縮合步驟。就是說，?；鶄?cè)鏈延伸的正確序列和延伸鏈的修飾是由存在于每一個(gè)組件上的遺傳信息決定的。
就除蟲菌素糖苷配基的生物合成機(jī)制而言，業(yè)已報(bào)導(dǎo)了與其他聚酮化合物相似，除蟲菌素糖苷配基的合成單元是以低級(jí)脂肪酸，如乙酸和丙酸為其成分[J.Antibiot.，39，541-549(1986)]，而在紅色糖多孢菌中，聚酮化合物合成酶由存在于產(chǎn)除蟲菌素細(xì)菌中的組件組成[基因，115，119-125(1992)，Ann.New York Acad.of Sci.721，123-132(1994)]。
日本公開的未經(jīng)過審查的專利申請(qǐng)?zhí)?5391/91披露了一種與除蟲菌素生物合成相關(guān)的DNA片段，但沒有提供該DNA片段的核苷酸序列。該公開文獻(xiàn)僅僅推測(cè)有聚酮化合物合成酶的存在，這種酶參與了除蟲菌素糖苷配基的合成，以及部分組件的存在。因此，無法預(yù)測(cè)除蟲菌素聚酮合成酶的完整結(jié)構(gòu)。
類似地，MacNeil等報(bào)導(dǎo)了部分組件的功能域結(jié)構(gòu)[Ann.New YorkAcad.of Sci.721，123-132(1994)]。不過，他們沒有披露作為除蟲菌素聚酮化合物合成酶的證據(jù)的核苷酸序列。
在培育能用于新工藝中的細(xì)菌菌株時(shí)，改變聚酮化合物合成酶可能是一種十分有用的育種技術(shù)，所述新工藝可用于生產(chǎn)能用作獸藥和農(nóng)藥的新型除蟲菌素，并可以生產(chǎn)更有效的除蟲菌素衍生物。實(shí)現(xiàn)所述改變所需要的步驟包括測(cè)定編碼聚酮化合物合成酶的基因的完整核苷酸序列，根據(jù)該序列準(zhǔn)確地確定每一組件的功能域結(jié)構(gòu)，并導(dǎo)入需要的突變。不過，如上文所述，在實(shí)施所述改進(jìn)的育種時(shí)是非常困難的，因?yàn)檫€不了解除蟲菌素糖苷配基的聚酮化合物合成酶基因，并且該基因的核苷酸序列也是未知的。
本發(fā)明人研究了通過改進(jìn)與各種方法的聚酮化合物合成相關(guān)的DNA生產(chǎn)不同于由野生型菌株所產(chǎn)生的成分的方法。為了采用本方法，首先，我們必須分離參與一種聚酮化合物生物合成的DNA分子。
因此，本發(fā)明的一個(gè)目的是提供一種編碼參與除蟲菌素糖苷配基生物合成的多功能酶的DNA，以及用所述DNA生產(chǎn)除蟲菌素糖苷配基、改變了的除蟲菌素糖苷配基、除蟲菌素、和改進(jìn)了的除蟲菌素的方法。

發(fā)明內(nèi)容
為實(shí)現(xiàn)上述目的，發(fā)明人進(jìn)行深入的研究。結(jié)果，本發(fā)明人成功地分離了編碼參與除蟲菌素糖苷配基生物合成的多功能酶的DNA。本發(fā)明就是基于這一結(jié)果而完成的。
本發(fā)明涉及下面的(1)-(43)。
(1)一種編碼除蟲菌素糖苷配基合成酶的DNA(以下又被稱作除蟲菌素糖苷配基合成酶基因)。
在本發(fā)明的一種實(shí)施方案中，所述DNA源于一種野生型產(chǎn)除蟲菌素菌株或其突變菌株，如屬于鏈霉屬的菌株，特別是除蟲鏈霉菌。
(2)一種含有選自下列一組的核苷酸序列的DNASEQ ID NO1的1-11916和11971-30688號(hào)核苷酸，和SEQ ID NO2的1-14643和14824-31419號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼一種具有除蟲菌素糖苷配基合成酶活性的多肽的DNA。
上述術(shù)語“一種能在嚴(yán)格條件下與該DNA雜交的DNA”是指利用具有SEQ ID NO1或2的核苷酸序列的DNA通過菌落雜交、噬菌斑雜交或Southern雜交獲得的，例如，所述DNA可以通過以下方法鑒定在65℃下，在有0.7-1.0摩爾/升氯化鈉存在的條件下，用在它上面固定了來自菌落或噬菌斑的DNA的濾膜進(jìn)行雜交，接著在65℃下用0.1-2×SSC溶液(1×SSC溶液含有150mM/升氯化鈉，15mM/升檸檬酸鈉)洗滌。
雜交可以按照在實(shí)驗(yàn)方案中所介紹的方法進(jìn)行，如分子克隆，實(shí)驗(yàn)室手冊(cè)，第2版，冷泉港實(shí)驗(yàn)室出版社，1989(以下簡(jiǎn)稱為分子克隆第2版)，當(dāng)代分子生物學(xué)方法，John Wiley&Sons，1987-1997(以下簡(jiǎn)稱為當(dāng)代分子生物學(xué)方法)，DNA克隆1；核心技術(shù)，實(shí)踐方法，第2版，牛津大學(xué)，1995?？梢噪s交的DNA的具體例子包括與選自下列一組的核苷酸序列至少具有80％，或更優(yōu)選95％或更高同源性的DNASEQ ID NO1的1-11916號(hào)核苷酸和11971-30688號(hào)核苷酸，和SEQ IDNO2的1-14643號(hào)核苷酸和14824-31419號(hào)核苷酸。
下面的術(shù)語“一種能在嚴(yán)格條件下與該DNA雜交的DNA”也可以按上文所述方式定義。
(3)如上述(1)或(2)的DNA，其中，該DNA包括編碼除蟲菌素糖苷配基合成酶功能域的DNA。
(4)如上述(3)的DNA，其中，該DNA編碼選自下列一組的除蟲菌素糖苷配基合成酶功能域一種編碼具有?；D(zhuǎn)移酶活性和酰基載體蛋白活性的多肽的DNA；一種編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、β-酮脂酰-ACP還原酶活性和?；d體蛋白活性的多肽的DNA；一種編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性和?；d體蛋白活性的多肽的DNA；一種編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、和酰基載體蛋白活性的多肽的DNA；和一種編碼具有β-酮脂酰-ACP合成酶活性、酰基轉(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、?；d體蛋白活性和硫酯酶活性的多肽的DNA。
(5)如上述(4)的DNA，其中，所述編碼具有?；D(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA是包括SEQ ID NO1的85-1353號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；D(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA。
(6)如上述(4)的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性、酰基轉(zhuǎn)移酶活性、β-酮脂酰-ACP還原酶活性、和?；d體蛋白活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1441-6180、15217-19938和20008-24690號(hào)核苷酸和SEQ ID NO2的100-4692和14935-20334號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、β-酮脂酰-ACP還原酶活性、和酰基載體蛋白活性的多肽的DNA。
(7)如上述(4)的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、和?；d體蛋白活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的6256-11658和24781-30309號(hào)核苷酸，和SEQ ID NO2的20413-25734和25810-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、和酰基載體蛋白活性的多肽的DNA。
(8)如上述(4)的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、和?；d體蛋白活性的多肽的DNA是一種包括SEQ ID NO1的12076-15147號(hào)核苷酸或SEQ ID NO2的4771-7818號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA。
(9)如上述(4)的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、?；d體蛋白活性、和硫酯酶活性的多肽的DNA是一種包括SEQ ID NO2的7906-14619號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、酰基轉(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、?；d體蛋白活性、和硫酯酶活性的多肽的DNA。
(10)如上述(4)的DNA，其中，所述編碼具有?；D(zhuǎn)移酶活性的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的85-1032、7906-8829、13756-14694、16917-17862、21658-22584和26413-27336號(hào)核苷酸，和SEQ ID NO2的1648-2673、6322-7344、9676-10773、16543-17565、21991-23019和27367-28392號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；D(zhuǎn)移酶活性的多肽的DNA。
(11)如上述(4)的DNA，其中，所述編碼具有?；d體蛋白活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1096-1353、5935-6180、11413-11658、14902-15147、19693-19938、24445-24690和30064-30309號(hào)核苷酸，和SEQ ID NO2的4447-4692、7573-7818、13378-13659、20089-20334、25489-25734和30880-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；d體蛋白活性的多肽的DNA。
(12)如上述(4)的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性的多肽的DNA是一種包括選自下列一組的核苷酸序列SEQ ID NO1的1441-2742、6256-7545、12076-13368、15217-16506、20008-21297和24781-26079號(hào)核苷酸，和SEQ ID NO1的100-1383、4771-6060、7906-9258、14935-16224、20413-21705和25810-27102號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性的多肽的DNA。
(13)如上述(4)的DNA，其中，所述編碼具有β-酮脂酰-ACP還原酶活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的5143-5676、10609-11142、18886-19419、23602-24138和29227-29760號(hào)核苷酸和SEQ ID NO2的3634-4188、12547-13104、19285-19842、24685-25242和30076-30633號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP還原酶活性的多肽的DNA。
(14)如上述(4)的DNA，其中，所述編碼具有脫水酶活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的8947-9384和27475-27894號(hào)核苷酸，和SEQ ID NO2的10885-11289、23149-23529和28516-28878號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有脫水酶活性的多肽的DNA。
(15)如上述(4)的DNA，其中，所述編碼具有硫酯酶活性的多肽的DNA是一種具有SEQ ID NO2的13879-14619號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有硫酯酶活性的多肽的DNA。
(16)如上述(3)或(4)的DNA，其中，所述編碼除蟲菌素糖苷配基合成酶功能域的DNA是一種編碼具有增強(qiáng)了的或減弱了的所述功能域的活性的多肽的突變型DNA。
(17)如上述(16)的DNA，其中，所述編碼具有減弱了的除蟲菌素糖苷配基合成酶功能域的活性的多肽的DNA，是包括SEQ IDNO7的核苷酸序列的DNA。
(18)一種編碼除蟲菌素糖苷配基合成酶功能域的DNA，它包括選自下列一組的核苷酸序列SEQ ID NO1的85-1032、1096-1353、1441-2742、3148-4068、5143-5676、5935-6180、6156-7545、7906-8829、8947-9384、10609、11142、11413、11658、12076-13368、13756-14694、14902-15147、15217-16506、16917-17862、18886-19419、19693-19938、20008-21297-21658-22584、23602-24138、24445-24690、24781-26079、26413-27335、27475-27894、29227-29760和300064-30309號(hào)核苷酸，和SEQ ID NO2的100-1383、1648-2673、3634-4188、4447-4692、4771-6060、6322-7344、7573-7818、7906-9258、9676-10773、10885-11289、12547-13104、13378-13659、13879-14619、14935-16224、16543-17565、17689-18066、19285-19842、20089-20334、20413-21705、21991-23019、23149-23529、24685-25242、25489-25734、25810-27102、27367-28392、28516-28878、30076-30633、和30880-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有除蟲菊素糖苷配基合成酶功能域活性的多肽的DNA。
(19)一種包括SEQ ID NO1的85-1353號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有酰基轉(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA。
(20)一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1441-6180、15217-19938和20008-24690號(hào)核苷酸，和SEQ ID NO2的100-4692號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、酰基轉(zhuǎn)移酶活性、β-酮脂酰-ACP還原酶活性和?；d體蛋白活性的多肽的DNA。
(21)一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的6256-11658和24781-30309號(hào)核苷酸，和SEQ ID NO2的14935-20334、20413-25734、和25810-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性和?；d體蛋白活性的多肽的DNA。
(22)一種包括SEQ ID NO1的12076-15147號(hào)核苷酸或SEQ IDNO2的4771-7818號(hào)核苷酸的核苷酸序列的DNA；一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA。
(23)一種包括SEQ ID NO2的7906-14619號(hào)核苷酸的核苷酸序列的DNA；一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、?；d體蛋白活性和硫酯酶活性的多肽的DNA。
(24)一種包括選自下列一組的核苷酸序列的DNA列1的85-1032、7906-8829、13756-14694、16917-17862、21658-22584和26413-27336號(hào)核苷酸，和SEQ ID NO2的1648-2673、6322-7344、9676-10773、16543-17565、21991-23019和27367-28392號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；D(zhuǎn)移酶活性的多肽的DNA。
(25)一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1096-1353、5935-6180、11413-11658、14902-15147、19693-19938、24445-24690和30064-30309號(hào)核苷酸，和SEQ ID NO2的4447-4692、7573-7818、13378-13659、20089-20334、25489-25734和30880-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；d體蛋白活性的多肽的DNA。
(26)一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1441-2742、6256-7545、12076-13368、15217-16506、20008-21297和24781-26079號(hào)核苷酸，和SEQ ID NO1的100-1383、4771-6060、7906-9258、14935-16224、20413-21705和25810-27102號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性的多肽的DNA。
(27)一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的5143-5676、10609-11142、18886-19419、23602-24138和29227-29760號(hào)核苷酸，和SEQ ID NO2的3634-4188、12547-13104、19285-19842、24685-25242、和30076-30633號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP還原酶活性的多肽的DNA。
(28)一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的8947-9384和27475-27894號(hào)核苷酸，和SEQ ID NO2的10885-10289、17689-18066、23149-23529和28516-28878號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有脫水酶活性的多肽的DNA。
(29)一種包括SEQ ID NO2的13879-14619號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有硫酯酶活性的多肽的DNA。
(30)一種包括SEQ ID NO7所示核苷酸序列的DNA。
(31)一種由上述(1)-(29)中任一項(xiàng)所述的DNA編碼的多肽。
(32)一種包括SEQ ID NO3-6中任一項(xiàng)的氨基酸序列的多肽；或一種包括在上述在SEQ ID NO3-6中任一項(xiàng)的氨基酸序列中缺失、取代或添加了一個(gè)或多個(gè)氨基酸的氨基酸序列，并且具有除蟲菊素糖苷配基合成酶活性的多肽。
上述“包括在上述選擇氨基酸序列中缺失、取代或添加了一個(gè)或多個(gè)氨基酸的氨基酸序列，并且具有除蟲菊素糖苷配基合成酶活性的多肽”可以按照披露于以下文獻(xiàn)中的定點(diǎn)誘變方法制備分子克隆，第2版，當(dāng)代分子生物學(xué)方法，核酸研究10，6487(1982)，美國科學(xué)院院報(bào)，79，6409(1982)，基因，34，315(1985)，核酸研究，13，4431(1985)，和美國科學(xué)院院報(bào)82，488(1985)等。缺失、取代或添加的氨基酸的數(shù)量沒有特別限制，不過，它是可以用已知方法缺失、取代或添加的氨基酸的數(shù)量，如上述定點(diǎn)誘變方法，并且在1-數(shù)十個(gè)氨基酸，優(yōu)選1-20，更優(yōu)選1-10，更優(yōu)選1-5個(gè)氨基酸。
(33)一種包括選自下列一組的氨基酸序列的多肽SEQ ID NO3的29-344、366-451、481-914、1050-1356、1715-1892、1979-2060、2086-2515、2983-3128、3537-3714和3805-3886號(hào)氨基酸，SEQ ID NO4的36-466、596-908、978-1059、1083-1512、1653-1964、2306-2483、2575-2653、2680-3109、32030-3538、3878-4056、4159-4240、4271-4303、4815-5122、5753-5930和6032-6113號(hào)氨基酸，SEQ ID NO5的34-461、550-891、1212-1396、1483-1564、1591-2020、2108-2448、2525-2606、2636-3086、3226-3591、3629-3763、4183-4363、4460-4553和4627-4873號(hào)氨基酸，SEQ ID NO6的38-467、574-914、956-1081、1488-1673、1756-1837、1864-2294、2390-3732、2776-2902、3288-3473、3556-3637、3663-4093、4182-4523、4565-4685、5085-5270和5353-5434號(hào)氨基酸；或一種包括在上述選擇氨基酸序列中缺失、取代或添加了一個(gè)或多個(gè)氨基酸的氨基酸序列，并且具有除蟲菊素糖苷配基合成酶功能域活性的多肽。
上述“一種包括在上述選擇氨基酸序列中缺失、取代或添加了一個(gè)或多個(gè)氨基酸的氨基酸序列，并且具有除蟲菊素糖苷配基合成酶功能域活性的多肽”可以按照上述(32)中所獲得的方法獲得。
(34)一種包括上述(1)-(30)中任一項(xiàng)的DNA的重組載體。
(35)一種通過將上述(1)-(30)中任一項(xiàng)的DNA或上述(34)中的重組載體導(dǎo)入宿主細(xì)胞而獲得的轉(zhuǎn)化體。
(36)如上述(35)的轉(zhuǎn)化體，其中，所述宿主細(xì)胞是產(chǎn)除蟲菊素細(xì)菌菌株。
(37)如上述(35)或(36)的轉(zhuǎn)化體，其中，所述宿主細(xì)胞是除蟲鏈霉菌K2038(FERM BP2775)。
(38)一種生產(chǎn)除蟲菊素糖苷配基合成酶或除蟲菊素糖苷配基合成酶功能域多肽的方法，包括在一種培養(yǎng)基中培養(yǎng)上述(35)-(37)中任一項(xiàng)的轉(zhuǎn)化體，以便在該培養(yǎng)基中形成并積累所述酶或功能域多肽，和從所述培養(yǎng)基回收所述酶或功能域多肽。
(39)一種生產(chǎn)除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基的方法，包括在一種培養(yǎng)基中培養(yǎng)上述(35)-(37)中任一項(xiàng)的轉(zhuǎn)化體，以便在該培養(yǎng)基中形成并積累所述除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基，和從所述培養(yǎng)基回收所述除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基。
(40)一種生產(chǎn)除蟲菊素或改變了的除蟲菊素的方法，包括在一種培養(yǎng)基中培養(yǎng)上述(35)-(37)中任一項(xiàng)的轉(zhuǎn)化體，以便在該培養(yǎng)基中形成并積累所述除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基，將所述除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基糖基化，和回收除蟲菊素或改變了的除蟲菊素。
(41)如上述(40)的方法，其中，改變了的除蟲菊素是一種從除蟲菊素B1a變成除蟲菊素B2a的除蟲菊素。
(42)一種可以通過上述(40)的方法所獲得的改變了的除蟲菊素。
(43)一種具有相當(dāng)于上述(1)或(2)中的DNA的核苷酸序列上的5-60個(gè)連續(xù)核苷酸的序列的寡核苷酸；或一種與所述寡核苷酸具有序列互補(bǔ)性的寡核苷酸。
附圖簡(jiǎn)述


圖1是限制酶圖譜，表示除蟲鏈霉菌的除蟲菊素糖苷配基合成酶基因aveAI和aveAII的BamHI、BglII、ClaI、EcoRI、KpnI、MluI、PstI、StuI和XhoI位點(diǎn)。每一個(gè)箭頭表示每一個(gè)預(yù)測(cè)的轉(zhuǎn)錄方向。
圖2表示(1)除蟲菊素糖苷配基合成酶基因的染色體位置和合成酶單位的功能域序列，(2)合成除蟲菊素糖苷配基的估計(jì)步驟，和(3)由聚酮合成酶所合成的6，8a-seco-6，8a-脫氧-5-氧代除蟲菊素糖苷配基的結(jié)構(gòu)，所述合成酶是除蟲菊素糖苷配基合成酶基因aveAI和aveAII的基因產(chǎn)物，以及整合到該化合物的骨架中的低級(jí)脂肪酸的位置。在該圖中，SU表示合成酶單位，ACP表示?；d體蛋白，AT表示?；D(zhuǎn)移酶，DH表示脫水酶，DH*表示脫水酶樣功能域，估計(jì)它是無活性的，KR表示β-酮脂酰-ACP還原酶，KR*表示β-酮脂酰-ACP還原樣功能域，估計(jì)它是有活性的，但不是體現(xiàn)在聚酮化合物合成反應(yīng)上，KS表示β-酮脂酰-ACP合成酶，TE表示硫酯酶。
發(fā)明詳述下面將對(duì)本發(fā)明進(jìn)行詳細(xì)說明。
本發(fā)明涉及編碼除蟲菊素糖苷配基合成酶的基因的DNA序列，以及一種生產(chǎn)除蟲菊素糖苷配基-除蟲菊素的基本組成單位-的方法。根據(jù)本發(fā)明，有可能生產(chǎn)一種新型的與除蟲菊素相關(guān)的化合物或除蟲菊素的特殊成分，這一目的是這樣實(shí)現(xiàn)的修飾所述DNA，以便改變參與在縮合反應(yīng)之后的修飾反應(yīng)的羧酸的類型和數(shù)量，或其任意組合。
1.制備本發(fā)明的DNA可以從諸如除蟲鏈霉菌的屬于鏈霉菌屬的細(xì)菌中分離編碼除蟲菊素糖苷配基合成酶的DNA(除蟲菊素糖苷配基合成酶基因)。
分離除蟲菊素糖苷配基合成酶基因的方法的例子包括披露于日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?5391/91中的方法，披露于分子克隆，第2版中的菌落雜交等。
具體的例子包括這樣一種方法，該方法包括將用諸如Sau3AI的合適的限制酶部分消化過的除蟲鏈霉菌的染色體DNA連接到在單一的限制酶位點(diǎn)上切開的、能在大腸桿菌中復(fù)制的粘粒載體上，例如，該載體用BamHI消化過；用所獲得的重組DNA轉(zhuǎn)化大腸桿菌；通過菌落雜交從所獲得的轉(zhuǎn)化體中篩選具有除蟲菊素糖苷配基合成酶基因的轉(zhuǎn)化體。
通過上述方法所獲得的DNA的例子包括具有SEQ ID NO1和2所示核苷酸序列的DNA。
偶然發(fā)現(xiàn)，具有SEQ ID NO1或2的核苷酸序列的DNA是編碼聚酮化合物合成酶的一部分的DNA片段，這樣，通過上述方法獲得了分離的編碼除蟲菊素B5-O-甲基轉(zhuǎn)移酶的基因(aveD)(基因，206，175-180，1988)。
可以通過與三種類型的紅霉素聚酮化合物合成酶功能域的序列進(jìn)行比較，確定與本發(fā)明的除蟲菊素糖苷配基合成酶基因相關(guān)的組件、功能域和ORFs(自然，348，176-178，1990，科學(xué)，252，675-679，1991，或歐洲生物化學(xué)雜志204，39-49，1992)。
圖1表示除蟲鏈霉菌的基因組DNA(～65kbp)的除蟲菊素糖苷配基合成酶基因片段(aveAI和aveAII)的限制圖譜，以及預(yù)測(cè)的轉(zhuǎn)錄單位(箭頭)。
聚酮化合物是具有多種結(jié)構(gòu)和功能的天然有機(jī)化合物，這種化合物的共同特征是，其合成是由被稱為聚酮化合物合成酶的多功能酶完成的。
一種聚酮化合物合成酶具有底物專一性，并能催化低級(jí)脂肪酸組成單位的延伸(它在除了起始反應(yīng)以外的反應(yīng)中以二羧酸的CoA酯的形式使用)，即縮合以便形成聚酮化合物并具有催化活性和控制活性，由這種活性修飾由所述反應(yīng)所產(chǎn)生的β-羰基基團(tuán)。
所述縮合反應(yīng)是聚酮化合物合成的基礎(chǔ)反應(yīng)，它需要各種催化活性，包括?；d體蛋白(ACP)活性，β-酮脂酰-ACP合成酶(KS)活性和?；D(zhuǎn)移酶(AT)活性。
在很多場(chǎng)合下，通過所述縮合反應(yīng)所產(chǎn)生的β-羰基基團(tuán)是修飾過的，不過，根據(jù)一種組件，某些β-羰基基團(tuán)可以不進(jìn)行修飾，并可以被用于下一個(gè)縮合反應(yīng)。
在所述縮合反應(yīng)之后，與修飾β-羰基基團(tuán)相關(guān)的催化活性包括β-酮脂酰-ACP還原酶(KR)活性，脫水酶(DH)活性，烯酰還原酶(ER)活性。聚酮化合物鏈的生物合成是通過硫酯酶(TE)活性的作用將所述聚酮化合物鏈從聚酮化合物合成酶上切除而終止的。
在每一個(gè)縮合過程中，有所述修飾活性的全部或若干種起作用，由此決定了最終產(chǎn)物的結(jié)構(gòu)。
除蟲鏈霉菌的除蟲菊素糖苷配基合成酶基因(aveAI和aveAII)的特征是具有若干開放讀框，每一個(gè)讀框包括一個(gè)或多個(gè)被稱為組件的重復(fù)單位，與其他已知的聚酮化合物生物合成基因類似。一個(gè)組件被定義為編碼一次合成的活性的基因片段，即一次縮合反應(yīng)，和隨后的β-羰基基團(tuán)的各種修飾反應(yīng)。每一個(gè)組件編碼與聚酮化合物合成中縮合反應(yīng)相關(guān)的ACP、KS和AT，以及與β-羰基基團(tuán)修飾反應(yīng)相關(guān)的KR、DH和ER中的全部或若干種。另外，還存在一種不具有修飾反應(yīng)的任何功能域的組件。一種編碼所述組件的多肽被稱為合成酶單位(SU)。
圖2表示由除蟲鏈霉菌的除蟲菊素糖苷配基合成酶所合成的6，8a-seco-6，8a-脫氧-5-氧代除蟲菊素糖苷配基的生物合成途徑。
很顯然，PKS1與起始反應(yīng)相關(guān)，因?yàn)槠鹗冀M件(SUs)與其他組件不同，它對(duì)N-末端一側(cè)具有酰基轉(zhuǎn)移酶(AT)活性。很顯然，PKS-3與聚酮化合物的最終反應(yīng)相關(guān)，因?yàn)榻M件9(SU9)具有硫酯酶(TE)功能域。
包括源于除蟲鏈霉菌的除蟲菊素糖苷配基合成酶基因的測(cè)定的DNA示于SEQ ID NO1和2中。本發(fā)明的DNA包括編碼相應(yīng)的多功能酶的開放讀框(ORFs)，和相應(yīng)于SEQ ID NO1的11-11916號(hào)核苷酸和21971和30688號(hào)核苷酸以及SEQ ID NO2的31-14643號(hào)核苷酸和414824-31419號(hào)核苷酸的OFRs。由上述序列所編碼的各種肽的氨基酸序列示于SEQ ID NO3、4、5和6中。
上述每一種DNA包括一個(gè)編碼一種合成單位的組件，所述合成單位具有完成一次碳鏈延伸反應(yīng)所必需的所有催化活性。所述組件由SEQID NO1和2中的核苷酸表示。就是說，SEQ ID NO1中所表示的組件為，起始組件85-1353，組件11441-6180，組件26256-11658，組件312076-15147，組件415217-19938，組件520008-24690，組件624781-30309，和在SEQ ID NO2中被表示為，組件7100-4692，組件84771-7818，組件7906-14619，組件1014935-20334，組件1120413-25734，組件1225810-31125。
由所述組件所編碼的各種合成酶單位(SU)的氨基酸序列用下面的氨基酸表示。就是說，在SEQ ID NO3中所表示的序列為，起始SU29-451，SU1481-2060，SU22086-3886；在SEQ ID NO4中為，SU336-1059，
SU41083-2656，SU52680-4240，SU64271-6113；在SEQ ID NO5中為，SU734-1564，SU81591-2606，SU92636-4873；和SEQ ID NO6中為，SU1038-1837，SU111864-3637，SU123663-5434。
編碼除蟲菊素糖苷配基合成酶功能域的DNA(亞組件)用下面的核苷酸表示。就是說，在SEQ ID NO1中表示的DNA為，在起始組件中，ATs85-1032，ACPs1096-1353；在組件1中，KS11441-2742，AT13148-4068，KR15143-5676，ACP15935-6180；在組件2中，KS26256-7545，AT27906-8829，DH28947-9384；KR10609-11142ACP211413-11658在組件3中，KS312076-13368，AT313756-14694，ACP314902-15147；在組件4中，
KS415217-16506，AT416917-17862KR418886-19419ACP419693-19938在組件5中，KS520008-21297，AT521658-22584KR523602-24138ACP524445-24690在組件6中，KS624781-26079AT626413-27336DH627475-27894KR629227-29760ACP630064-30309；和在SEQ ID NO2中為，在組件7中，KS7100-1383，AT71648-2673，KR73634-4188ACP74447-4692在組件8中，KS84771-6060，AT86322-7344，ACP87573-7818；在組件8中，KS97906-9258，AT99676-10773，DH910885-11289，KR912547-13104，ACP913378-13659，TE913879-14619；
在組件10中，KS1014935-16224，AT1016543-17565，DH1017689-18066，KR1019285-19842，ACP1020089-20334；在組件11中，KS1120413-21705，AT1121991-23019，DH1123149-23529，KR1124685-25242，ACP1125489-25734；在組件12中，KS1225810-27102，AT1227367-28392，DH1228516-28878，KR1230076-30633，ACP1230880-31125。
由所述亞組件編碼的各種功能域的推測(cè)的氨基酸序列為在SEQ ID NO3中，ATs29-334，ACPs366-451，KS1481-914，AT11050-1356，KR11715-1892，ACP11979-2060，KS22086-2515，DH22983-3128，KR23537-3714，ACP23805-3886；在SEQ ID NO4中，KS336-466，
AT3596-908，ACP3978-1059，KS41083-1512，AT41653-1964，KR42306-2483，ACP42575-2656，KS52680-3109，AT532030-3538，KR53878-4056，ACP54159-4240，KS64271-4703，AT64815-5122，DH65753-5930，ACP66032-6113；在SEQ ID NO5中，KS734-461，AT7550-891，KR71212-1396，ACP71483-1564，KS81591-2020，AT82108-2448，ACP82525-2606，KS92636-3086，AT93226-3591，DH93629-3763，KR94183-4363，ACP94460-4553；TE94627-4873；和在SEQ ID NO6中，KS1038-467，AT10574-914，DH10956-1081，
KR101488-1673，ACP101756-1837，KS111864-2294，AT112390-2732，DH112776-2902，KR113288-3473，ACP113556-3637，KS123663-4093，AT124182-4523，DH124565-4685，KR125085-5270，ACP125353-5434。
通過比較與已知聚酮化合物合成酶基因有關(guān)的序列信息發(fā)現(xiàn)，在具有相同功能的功能域之間存在序列相似性。通過利用所述相似性，可以推測(cè)一種新型聚酮化合物合成酶基因的功能域。
換句話說，根據(jù)上述組件，可以確定從源于除蟲鏈霉菌的、具有SEQ ID NO1和2的核苷酸序列的DNA所獲得的功能域和ORF信息，與源于能夠產(chǎn)生除蟲菌素的其他細(xì)菌的，本發(fā)明的除蟲菊素糖苷配基合成酶基因相關(guān)的組件、功能域和ORFs。
使用具有SEQ ID NO1或2的核苷酸序列的DNA，可以通過以下方法獲得除蟲菊素糖苷配基合成酶基因。
用合適的限制酶消化具有SEQ ID NO1或2的核苷酸序列的DNA，分離DNA片段，并通過披露于分子克隆，第2版中的方法回收，并將由所述DNA片段組成的寡核苷酸用作探針或引物。
作為探針，優(yōu)選使用用洋地黃毒苷等標(biāo)記過的DNA片段?？蓪IG標(biāo)記&檢測(cè)試劑盒用于洋地黃毒苷標(biāo)記，該試劑盒可以從RocheDiagnostic公司購買。
通過披露于分子克隆，第2版等中的基因組克隆或cDNA克隆，由產(chǎn)生除蟲菌素的細(xì)菌制備文庫。
從上述文庫中選擇能與按上述方法獲得的探針雜交的克隆(或菌落)，然后通過披露分子克隆，第2版等中的方法從所述克隆中提取質(zhì)粒，并可最終由所述質(zhì)粒獲得除蟲菌素糖苷配基合成酶基因。另外，可以通過相同的方法獲得編碼除蟲菌素糖苷配基合成酶基因功能域的DNA(即亞組件)和組件。
另外，還可以通過用按上述方法制備的上述文庫和引物進(jìn)行直接PCR擴(kuò)增獲得除蟲菌素糖苷配基合成酶基因、亞組件和組件。
在按上述方法提取的質(zhì)粒中僅存在編碼除蟲菌素糖苷配基合成酶的部分DNA片段情況下，按照標(biāo)準(zhǔn)技術(shù)通過用諸如BamHI的合適的限制酶消化提取的質(zhì)粒制備該質(zhì)粒的限制圖譜。
可以按以下方法制備包括編碼完整除蟲菌素聚酮化合物合成酶的DNA的DNA限制酶圖譜尋找普遍存在于若干克隆中的限制酶片段，并在重疊部分結(jié)合所述克隆的片段，因此可以獲得編碼除蟲菌素聚酮化合物合成酶的DNA。
可以通過被普遍采用的核苷酸分子方法測(cè)定編碼除蟲菌素聚酮化合物合成酶的DNA的核苷酸序列，例如，雙脫氧方法(美國科學(xué)院院報(bào)，74，5463，1977)，或用諸如373A DNA測(cè)序儀(Perkin Elmer公司)的DNA測(cè)序分析儀分析。
具體地講，可以通過直接用雙鏈質(zhì)粒DNA作模板進(jìn)行一輪測(cè)序反應(yīng)測(cè)定DNA序列，其中，使用對(duì)各種序列專一的寡核苷酸引物?；蛘撸€可以通過以下方法測(cè)定DNA序列將一種DNA片段裂解成小片段；將所得到的片段隨機(jī)導(dǎo)入細(xì)菌噬菌體M13；用包括部分重疊的片段的文庫或質(zhì)粒載體制備一種重疊文庫，該文庫包括從其末端連續(xù)缺失的DNA片段；用對(duì)所述載體序列專一的寡核苷酸引物對(duì)每一種重組DNA進(jìn)行DNA測(cè)序?？梢杂靡环NDNA測(cè)序儀(例如，用Model4000L，LiCor)分析通過循環(huán)測(cè)序反應(yīng)所獲得的熒光標(biāo)記過的反應(yīng)劑。
另外，根據(jù)測(cè)定DNA的核苷酸序列，還可以使用DNA合成儀(Model8905，Perceptive BioSystems)等通過化學(xué)合成制備所需的DNA。
可以用現(xiàn)有的軟件，例如，GenetyxTM(軟件開發(fā))對(duì)所獲得的核苷酸序列數(shù)據(jù)進(jìn)行排列、編輯和分析。
利用通過上述方法所獲得的本發(fā)明的DNA和DNA片段，可以按照標(biāo)準(zhǔn)技術(shù)制備諸如反義寡核苷酸和有義寡核苷酸的寡核苷酸，它具有本發(fā)明的DNA序列的一部分，或者包括一種RNA的寡核苷酸。另外，根據(jù)上面所獲得的DNA序列信息，還可以用上述DNA合成儀合成所述寡核苷酸。
由此所獲得的寡核苷酸的例子包括具有相當(dāng)于通過上述方法所獲得的DNA的核苷酸序列上的5-60個(gè)連續(xù)核苷酸的序列的DNA，或具有互補(bǔ)于該DNA的序列的DNA。另外，本發(fā)明的寡核苷酸還包括具有互補(bǔ)于所述DNA的序列的RNA。
由此所獲得的寡核苷酸的例子包括相當(dāng)于SEQ ID NO1或2的核苷酸序列上的5-60個(gè)連續(xù)核苷酸的序列的DNA，或具有互補(bǔ)于該DNA的序列的DNA。當(dāng)將上述寡核苷酸中的某種寡核苷酸用作有義和反義引物時(shí)，優(yōu)選采用這樣的寡核苷酸，其中，其解鏈溫度(Tm)和堿基數(shù)在兩種寡核苷酸之間沒有明顯差別。
由此所獲得的寡核苷酸的例子包括具有SEQ ID NO9-14所示核苷酸序列的寡核苷酸。
另外，還可將所述寡核苷酸的衍生物(以下又稱之為寡核苷酸衍生物)用作本發(fā)明的寡核苷酸。
所述寡核苷酸衍生物的例子包括通過將上述寡核苷酸中的磷酸二酯磷酸鍵轉(zhuǎn)化成硫代磷酸鍵而獲得的寡核苷酸衍生物；通過將上述寡核苷酸中的磷酸二酯鍵轉(zhuǎn)化成N3’-P5’磷酰胺鍵而獲得的寡核苷酸衍生物；通過將上述寡核苷酸中的核糖和磷酸二酯磷酸鍵轉(zhuǎn)化成肽核酸鍵而獲得的寡核苷酸衍生物；通過用C-5 propynyl尿嘧啶取代上述寡核苷酸中的尿嘧啶而獲得的寡核苷酸衍生物；通過用C-5 propynyl胞嘧啶取代上述寡核苷酸中的胞嘧啶而獲得的寡核苷酸衍生物；通過用吩惡嗪修飾過的胞嘧啶取代上述寡核苷酸中的胞嘧啶而獲得的寡核苷酸衍生物；通過用2’-O-丙基核糖取代上述寡核苷酸中的核糖而獲得的寡核苷酸衍生物；和通過用2’-甲氧基乙氧基核糖取代上述寡核苷酸中的核糖而獲得的寡核苷酸衍生物等(細(xì)胞工程(Saibo Kogaku)16，1463，1997)。
2.制備本發(fā)明的多肽本發(fā)明的多肽可以用披露于分子克隆第2版或當(dāng)代分子生物學(xué)方法中的方法生產(chǎn)。例如，可以按照下述方法通過在宿主細(xì)胞中表達(dá)按第1節(jié)中所述方法獲得的本發(fā)明的DNA而生產(chǎn)。
根據(jù)本發(fā)明的DNA，如果必要，可以制備含有編碼本發(fā)明多肽的片段的合適長度的DNA片段。另外，可以通過以下方法制備可用于改善所述多肽的生產(chǎn)效率的DNA取代編碼所述多肽的片段的核苷酸序列上的一個(gè)核苷酸，以便使得一種密碼子最適合在宿主細(xì)胞中表達(dá)。
將所述DNA片段插在一種合適表達(dá)載體上的一個(gè)啟動(dòng)子下游的位點(diǎn)上，以便構(gòu)建一種重組載體。
將所述重組載體導(dǎo)入適于所述表達(dá)載體的宿主細(xì)胞中，以便能夠獲得能產(chǎn)生本發(fā)明多肽的轉(zhuǎn)化體。
作為宿主細(xì)胞，可以使用能表達(dá)所述目的基因的任何細(xì)菌細(xì)胞、酵母細(xì)胞、動(dòng)物細(xì)胞、昆蟲細(xì)胞、植物細(xì)胞等。
作為表達(dá)載體，可以使用能在上述宿主細(xì)胞中自主復(fù)制或能夠整合到其染色體上的任何載體，并且它在適于本發(fā)明DNA轉(zhuǎn)錄的位點(diǎn)上含有一個(gè)啟動(dòng)子。
當(dāng)原核細(xì)胞(例如，細(xì)菌細(xì)胞)被用作宿主細(xì)胞時(shí)，本發(fā)明多肽的優(yōu)選表達(dá)載體可以是能夠在原核細(xì)胞中自主復(fù)制的重組DNA結(jié)構(gòu)，并且它包括一個(gè)啟動(dòng)子、一個(gè)核糖體結(jié)合序列、本發(fā)明的DNA和一個(gè)終止子。所述載體還可以包括調(diào)控所述啟動(dòng)子的基因。
表達(dá)載體的例子包括pBTrp2，pBTac1，pBTac2(均由BoehringerMannheim生產(chǎn))，pKK233-2(由Pharmacia生產(chǎn))，pGEX(由Pharmacia生產(chǎn))，pSE280(由Invitrogen生產(chǎn))，pGEME-1(由Promega生產(chǎn))，pQE-8(由Qingen生產(chǎn))，pQE-9(由Qingen生產(chǎn))，pQE-70(由Qingen生產(chǎn))，pQE-60(由Qingen生產(chǎn))，pET-3(由Novagen生產(chǎn))，pET-11a(由Novagen生產(chǎn))，pKYP10(日本公開的未經(jīng)審查的專利申請(qǐng)110600/83)，pKYP200[農(nóng)業(yè)生物學(xué)化學(xué)48，669，1984]，pLSA1[農(nóng)業(yè)生物學(xué)化學(xué)53，277，1989]，pGEL1[美國科學(xué)院院報(bào)，82，4306，1985]，pBluescript II SK+(由Stratagene生產(chǎn))，pBluescript II SK(-)(由Stratagene生產(chǎn))，pTrS30[由大腸桿菌JM109制備/pTrS30(FERMBP-5407)]，pTrS32[由大腸桿菌JM109制備/pTrS32(FERMBP-5408)]，pUC19[基因，33，103，1985]，pSTV28(由TakaraShuzo有限公司生產(chǎn))，pUC118(由Takara Shuzo有限公司生產(chǎn))，pPA1(日本公開的未經(jīng)審查的專利申請(qǐng)233798/88)，pKC30(Rosenberg等，1983，參見酶學(xué)方法，101卷，123-138頁，學(xué)術(shù)出版社，San Diego)，pKK223-3(由Pharmacia生產(chǎn))，pDR540(由Pharmacia生產(chǎn))，pRIT2T(由Pharmacia生產(chǎn))，和ptrc99a[基因，69，301，1988]。
作為啟動(dòng)子，可以使用能夠在諸如大腸桿菌的宿主細(xì)胞中表達(dá)的任何啟動(dòng)子，包括源于大腸桿菌或噬菌體的啟動(dòng)子，如trp啟動(dòng)子(如Ptrp)，lac啟動(dòng)子(Plac)，PL啟動(dòng)子，PR啟動(dòng)子，和PSE啟動(dòng)子，SPO1啟動(dòng)子，SPO2啟動(dòng)子，和penP啟動(dòng)子。還可以使用人工設(shè)計(jì)的，修飾過的啟動(dòng)子，包括通過以串聯(lián)方式連接兩個(gè)Ptrp啟動(dòng)子所獲得的啟動(dòng)子(Ptrp×2)，tac啟動(dòng)子，lacT7啟動(dòng)子，和letI啟動(dòng)子。
優(yōu)選使用在SD序列(即核糖體結(jié)合序列)和起始密碼子之間具有合適距離(例如，6-28個(gè)堿基)的質(zhì)粒。
對(duì)于本發(fā)明重組DNA結(jié)構(gòu)的表達(dá)來說，終止子不是必需的，不過，優(yōu)選在僅挨著結(jié)構(gòu)基因下游的位置上有一個(gè)終止密碼子。
原核生物包括屬于埃希氏菌屬、沙雷氏菌屬、芽孢桿菌屬、短桿菌屬、棒桿菌屬、微桿菌屬和假單胞菌屬等的微生物。具體例子包括大腸桿菌XL1-Blue，大腸桿菌XL1-Blue，大腸桿菌DH1，大腸桿菌MC1000，大腸桿菌KY3276，大腸桿菌W1485，大腸桿菌JM109，大腸桿菌HB101，大腸桿菌No.49，大腸桿菌W3110，大腸桿菌NY49，無花果沙雷氏菌，居泉沙雷氏菌，液化沙雷氏菌，粘質(zhì)沙雷氏菌，枯草芽孢桿菌，解淀粉芽孢桿菌，產(chǎn)氨短桿菌，B.immariophilumATCC14068，解糖短桿菌ATCC14066，谷氨酸棒桿菌ATCC13032，谷氨酸棒桿菌ATCC14067，谷氨酸棒桿菌ATCC13869，嗜乙酰乙酸棒桿菌ATCC13870，嗜氨微桿菌ATCC15354，和假單胞菌D-0110。
重組DNA的導(dǎo)入，可以通過用于將DNA導(dǎo)入所述宿主細(xì)胞的任何方法完成例如，鈣離子方法[美國科學(xué)院院報(bào)，69，2110，1972]，原生質(zhì)體方法(日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?48394/88)和電穿孔[核酸研究，16，6127，1988]。
當(dāng)酵母細(xì)胞被用作宿主細(xì)胞時(shí)，可以使用的表達(dá)載體包括Yep13(ATCC37115)、Yep24(ATCC37051)、Ycp50(ATCC37419)、pSH19、pSH15、G-1、pXT1(由Stratagene生產(chǎn))、pG5(由Stratagene生產(chǎn))、pSVK3(由Pharmacia生產(chǎn))、pBPV、pMSG(由Pharmacia生產(chǎn))、和pSVLSV40(由Pharmacia生產(chǎn))。
作為啟動(dòng)子，可以使用能在酵母細(xì)胞中表達(dá)的任何啟動(dòng)子，包括PHO5啟動(dòng)子、PGK啟動(dòng)子、GAP啟動(dòng)子、ADH啟動(dòng)子、GDP啟動(dòng)子、AOX1啟動(dòng)子、gal1啟動(dòng)子、gal10啟動(dòng)子、熱激多肽啟動(dòng)子、MFα1啟動(dòng)子、和CUP1啟動(dòng)子。
宿主細(xì)胞的例子包括屬于酵母屬、裂殖酵母屬、克魯維酵母屬、絲胞酵母屬、許旺酵母屬、和畢赤酵母屬等的酵母菌株。具體例子包括釀酒酵母、粟酒裂殖酵母、乳酸克魯維酵母、茁芽絲胞酵母、河岸許旺酵母、或巴斯德畢赤酵母。
所述重組DNA的導(dǎo)入可以通過用于將DNA導(dǎo)入酵母細(xì)胞的任何方法完成，例如，電穿孔[酶學(xué)方法，194，182，1990]、原生質(zhì)球方法[美國科學(xué)院院報(bào)，81，4889，1984]、乙酸鋰方法[細(xì)菌學(xué)雜志，153，163]和披露于美國科學(xué)院院報(bào)中的方法，75，1929，1978。
當(dāng)動(dòng)物細(xì)胞被用作宿主細(xì)胞，可以使用的表達(dá)載體包括pcDNAI、pcDM8(由Funakoshi出售)、pAGE107(日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?2979/91)、pAS3-3(日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?27075/90)、pCDM8[自然，329，840，1987]、pcDNAI/Amp(由Invitrogen生產(chǎn))、pREP4(由Invitrogen生產(chǎn))、pAGE103[生物化學(xué)雜志，101，1307，1987]、pAGE210、pAMo、和pAMoA。
作為啟動(dòng)子，可以使用能在動(dòng)物細(xì)胞中表達(dá)的任何啟動(dòng)子，包括巨細(xì)胞病毒(CMV)的立即早期(IE)基因的啟動(dòng)子、SV40早期啟動(dòng)子或金屬硫蛋白啟動(dòng)子、逆轉(zhuǎn)錄病毒啟動(dòng)子、熱激啟動(dòng)子和SRα啟動(dòng)子。還可將人類CMV的IE基因的增強(qiáng)子與所述啟動(dòng)子一起使用。
宿主細(xì)胞包括小鼠骨髓瘤細(xì)胞、大鼠骨髓瘤細(xì)胞、小鼠雜交瘤細(xì)胞、人類Namalwa或Namalwa KJM1細(xì)胞、人類胎兒腎細(xì)胞、人類白血病細(xì)胞、非洲綠猿腎細(xì)胞、中國倉鼠CHO細(xì)胞、或HBT5637(日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?99/88)。
小鼠骨髓瘤細(xì)胞的具體例子包括SP2/O、和NSO等，大鼠骨髓瘤細(xì)胞的具體例子包括YB2/O，人類胎兒腎細(xì)胞的具體例子包括HEK293(ATCCCRL-1573)、和293等。人類白血病細(xì)胞的具體例子包括BALL-1，非洲綠猿腎細(xì)胞的具體例子包括COS-1、和COS-7等。
所述重組DNA的導(dǎo)入可以通過用于將DNA導(dǎo)入動(dòng)物細(xì)胞的任何方法完成例如，電穿孔[細(xì)胞技術(shù)，3，133，1990]、磷酸鈣方法(日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?27075/90)、脂轉(zhuǎn)染方法[美國科學(xué)院院報(bào)，84，7413，1987]和披露于病毒學(xué)，52，456，1973中的方法。
當(dāng)將昆蟲細(xì)胞用作宿主細(xì)胞時(shí)，可以通過披露于以下文獻(xiàn)中的方法表達(dá)一種多肽桿狀病毒表達(dá)載體，實(shí)驗(yàn)室手冊(cè)，W.H.Freeman andCompany，紐約(1992)；當(dāng)代分子生物學(xué)方法；分子生物學(xué)，實(shí)驗(yàn)室手冊(cè)；或生物技術(shù)，6，47(1988)。
更具體地講，可以將重組基因轉(zhuǎn)移載體和桿病毒共同導(dǎo)入昆蟲細(xì)胞中，以便獲得存在于來自培養(yǎng)的昆蟲細(xì)胞上清液中的重組病毒。然后，可以用所得到的重組病毒進(jìn)一步感染昆蟲細(xì)胞，以便表達(dá)所述多肽。
用于上述方法中的基因轉(zhuǎn)移載體的例子包括pVL1392、pVL1393、和pBlueBacIII(分別由Invitrogen出售)等。
桿狀病毒的例子包括苜蓿銀紋夜蛾核型多角體病毒，它能感染夜蛾科等。
昆蟲細(xì)胞的例子包括草地夜蛾卵巢細(xì)胞、粉紋夜蛾卵巢細(xì)胞、源于家蠶卵巢的培養(yǎng)細(xì)胞等。
草地夜蛾卵巢細(xì)胞的具體例子為Sf9和Sf21(桿病毒表達(dá)載體，實(shí)驗(yàn)室手冊(cè))，粉紋夜蛾卵巢細(xì)胞的具體例子為High5和BTI-TN-581-4(由Invitrogen生產(chǎn))、源于家蠶卵巢的培養(yǎng)細(xì)胞的具體例子為家蠶N4等。
可以通過磷酸鈣方法(日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?27075/90)或脂轉(zhuǎn)染方法[美國科學(xué)院院報(bào)，84，7413，1987]將所述重組基因轉(zhuǎn)移載體和桿病毒共同導(dǎo)入昆蟲細(xì)胞，以便進(jìn)行重組病毒生產(chǎn)。
當(dāng)植物細(xì)胞被用作宿主細(xì)胞時(shí)，表達(dá)載體的例子包括Ti質(zhì)粒、和煙草花葉病毒載體等。
作為啟動(dòng)子，可以使用能在植物細(xì)胞中表達(dá)的任何啟動(dòng)子，包括花椰菜花葉病毒(CaMV)35S啟動(dòng)子，和水稻肌動(dòng)蛋白1啟動(dòng)子等。
宿主細(xì)胞包括植物細(xì)胞，如煙草、馬鈴薯、番茄、胡蘿卜、大豆、蕓薹屬、苜蓿、水稻、小麥、和大麥等。
所述重組載體的導(dǎo)入可以通過用于將DNA導(dǎo)入植物細(xì)胞中的任何方法完成例如，農(nóng)桿菌屬方法(日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?40885/84，日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?0080/85，WO94/00977)、電穿孔(日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?51887/85)、和粒子槍方法(日本專利申請(qǐng)?zhí)?856，日本專利申請(qǐng)?zhí)?517813)。
根據(jù)披露于分子克隆第2版中的方法，所述基因可以直接表達(dá)，或者作為一種分泌型多肽或融合多肽形式表達(dá)。在酵母、動(dòng)物、昆蟲或植物細(xì)胞中的表達(dá)可以提供一種在它上面結(jié)合了糖或糖鏈的多肽。
本發(fā)明的多肽可以通過以下方法生產(chǎn)在一種培養(yǎng)基中培養(yǎng)由此獲得的轉(zhuǎn)化體，以便在該培養(yǎng)基中產(chǎn)生并積累本發(fā)明的多肽，以及從該培養(yǎng)基中回收所述多肽。
本發(fā)明的轉(zhuǎn)化體可以按照用于培養(yǎng)宿主細(xì)胞的常規(guī)方法在一種培養(yǎng)基中培養(yǎng)。
用于培養(yǎng)源于原核宿主(例如，大腸桿菌)或真核宿主(例如，酵母)的轉(zhuǎn)化體的培養(yǎng)基可以是天然的或合成的培養(yǎng)基，如含有碳源、氮源、無機(jī)鹽等的培養(yǎng)基，它能夠被有關(guān)生物同化，并能有效培養(yǎng)所述轉(zhuǎn)化體。
能夠被有關(guān)生物同化的任何碳源都可以用作碳源。說明性的例子包括碳水化合物，如葡萄糖、果糖、蔗糖、含有以上成分的糖漿、淀粉或淀粉水解產(chǎn)物；有機(jī)酸，如乙酸、丙酸；醇，如乙醇和丙醇等。
可以使用的氮源的例子包括各種無機(jī)或有機(jī)酸的銨鹽，如氨、氯化銨、硫酸銨、乙酸銨和磷酸銨；或含氮化合物；和胨、肉類提取物、酵母提取物、玉米漿、酪蛋白水解產(chǎn)物、大豆粉、大豆粉水解產(chǎn)物；各種發(fā)酵的細(xì)胞及其水解產(chǎn)物等。
可以使用的無機(jī)鹽包括磷酸二氫鉀、磷酸氫二鉀、磷酸鎂、硫酸鎂、氯化鈉、硫酸鐵、硫酸錳、硫酸銅和碳酸鈣等。
培養(yǎng)是在有氧條件下通過搖動(dòng)培養(yǎng)、在通氣條件下的深層旋動(dòng)培養(yǎng)完成的。培養(yǎng)溫度優(yōu)選為15-40℃，培養(yǎng)時(shí)間通常為5小時(shí)-7天。在培養(yǎng)期間，將pH保持在3.0-9.0。pH可以通過無機(jī)或有機(jī)酸、堿性溶液、尿素、碳酸鈣、和氨等調(diào)整。
另外，如果必要，在培養(yǎng)期間可以將諸如氨芐青霉素和四環(huán)素的抗生素添加到培養(yǎng)基中。
當(dāng)用一種含有誘導(dǎo)型啟動(dòng)子的表達(dá)載體轉(zhuǎn)化微生物時(shí)，如果必要，可以在補(bǔ)充了一種誘導(dǎo)物的培養(yǎng)基中培養(yǎng)轉(zhuǎn)化體。例如，當(dāng)含有l(wèi)ac啟動(dòng)子的表達(dá)載體被用于轉(zhuǎn)化時(shí)，可以在添加了異丙基β-D-硫代半乳糖吡喃糖苷等的培養(yǎng)基中培養(yǎng)轉(zhuǎn)化體；當(dāng)含有trp啟動(dòng)子的表達(dá)載體用于轉(zhuǎn)化時(shí)，可以在添加了吲哚乙酸等的培養(yǎng)基中培養(yǎng)轉(zhuǎn)化體。
用于培養(yǎng)用動(dòng)物細(xì)胞作為宿主所獲得的轉(zhuǎn)化體的培養(yǎng)基包括常用培養(yǎng)基，如RPMI1640培養(yǎng)基[美國醫(yī)學(xué)協(xié)會(huì)雜志，199，519，1967]、Eagle’s MEN培養(yǎng)基[科學(xué)，122，501，1952]、DMEM培養(yǎng)基[病毒學(xué)，8，396，1959]、199培養(yǎng)基[生物學(xué)醫(yī)學(xué)協(xié)會(huì)進(jìn)展，73，1，1950]，以及在上述培養(yǎng)基中添加了胎牛血清等的其他培養(yǎng)基。
培養(yǎng)通常是在存在5％二氧化碳的條件下在pH6-8，溫度為25-40℃下進(jìn)行1-7天。
另外，如果必要，在培養(yǎng)期間可以向培養(yǎng)基中添加諸如卡那霉素、青霉素和鏈霉素的抗生素。
用于培養(yǎng)用昆蟲細(xì)胞作宿主所獲得的轉(zhuǎn)化體的培養(yǎng)基包括常用的培養(yǎng)基，如TNM-FH培養(yǎng)基(由PharMingen生產(chǎn))、Sf-900II SFM培養(yǎng)基(由生命技術(shù)公司生產(chǎn))、ExCell400和ExCell405[均為GRH生物科學(xué)公司的產(chǎn)品]、或Grace’s昆蟲培養(yǎng)基[自然，195，788，1965]等。
培養(yǎng)通常是在pH6-7，溫度為25-30℃的條件下進(jìn)行1-5天。
另外，如果必要，在培養(yǎng)期間可以向培養(yǎng)基中添加諸如慶大霉素的抗生素。
用植物細(xì)胞作宿主所獲得的轉(zhuǎn)化體可以細(xì)胞形式培養(yǎng)，或在培養(yǎng)之前使其分化成植物細(xì)胞或器官。用于培養(yǎng)所述轉(zhuǎn)化體培養(yǎng)基的例子包括常用培養(yǎng)基，如MS培養(yǎng)基、White培養(yǎng)基、或另外補(bǔ)充了諸如生長素或細(xì)胞激動(dòng)素的植物激素的上述培養(yǎng)基的任一種。
培養(yǎng)通常是在pH5-9，溫度為20-40℃的條件下進(jìn)行3-60天。
另外，如果必要，在培養(yǎng)期間可以向培養(yǎng)基中添加諸如卡那霉素和潮霉素的抗生素。
如上文所述，本發(fā)明的多肽可以這樣生產(chǎn)培養(yǎng)由微生物-、動(dòng)物細(xì)胞-、或植物細(xì)胞-產(chǎn)生的具有重組載體的轉(zhuǎn)化體，其中，按一般方法在所述載體上插入了編碼本發(fā)明多肽的DNA，以便產(chǎn)生并積累所述多肽，然后從所述培養(yǎng)基中回收所述多肽。
用于生產(chǎn)本發(fā)明多肽的方法包括在宿主細(xì)胞中進(jìn)行細(xì)胞內(nèi)生產(chǎn)，通過宿主細(xì)胞進(jìn)行細(xì)胞外分泌或在宿主細(xì)胞外膜上生產(chǎn)，并且所述方法可以根據(jù)要使用的宿主細(xì)胞類型和/或要生產(chǎn)的多肽的結(jié)構(gòu)進(jìn)行選擇。
如果本發(fā)明的多肽是在宿主細(xì)胞內(nèi)或在宿主細(xì)胞外膜上生產(chǎn)的話，可以用以下方法將所述多肽從宿主細(xì)胞中有效地分泌到細(xì)胞外Paulson等[生物學(xué)化學(xué)雜志，164，17619，1989]，Lowe等[美國科學(xué)院院報(bào)，86，8227，1989，基因發(fā)育，4，1288，1990]或日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?36963/93和PCT WO94/23021。
更具體地講，本發(fā)明的多肽可以通過利用遺傳重組技術(shù)，以具有信號(hào)肽的形式表達(dá)而從宿主細(xì)胞中有效地分泌，所述信號(hào)肽被添加在含有本發(fā)明多肽的活性位點(diǎn)的部分的上游。
另外，可以按照披露于日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?27075/90中的方法，利用采用了二氫葉酸還原酶基因的基因擴(kuò)增系統(tǒng)提高其產(chǎn)量。
另外，可以讓導(dǎo)入了一個(gè)基因的動(dòng)物或植物細(xì)胞再分化，以便產(chǎn)生具有轉(zhuǎn)基因的動(dòng)物個(gè)體(轉(zhuǎn)基因非人動(dòng)物)或具有轉(zhuǎn)基因的植物個(gè)體(轉(zhuǎn)基因植物)，可將其用于生產(chǎn)本發(fā)明的多肽。
當(dāng)轉(zhuǎn)化體是動(dòng)物或植物個(gè)體時(shí)，可以按以下方法獲得所述多肽用一般方法飼養(yǎng)或培養(yǎng)所述個(gè)體，以便產(chǎn)生并積累所述多肽，然后從所述動(dòng)物或植物個(gè)體中回收所述多肽。
用動(dòng)物個(gè)體生產(chǎn)本發(fā)明多肽的方法包括使用通過用披露于以下文獻(xiàn)中的已知方法導(dǎo)入基因而獲得的動(dòng)物的方法美國臨床營養(yǎng)雜志，63，639S，1996；美國臨床營養(yǎng)雜志，63，627S，1996，和生物技術(shù)，9，830，1991。
例如，對(duì)于動(dòng)物個(gè)體來說，本發(fā)明的多肽可以按以下方法獲得飼養(yǎng)導(dǎo)入了編碼本發(fā)明多肽的DNA插入片段的轉(zhuǎn)基因非人動(dòng)物，以便在其體內(nèi)產(chǎn)生并積累所述多肽。然后從該動(dòng)物體內(nèi)回收所述多肽。所述多肽可以在動(dòng)物的乳液(日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?09192/88)、和卵中生產(chǎn)并積累。作為用于這一目的的啟動(dòng)子，可以使用任何啟動(dòng)子，只要它能在所述動(dòng)物體內(nèi)表達(dá)即可。例如，哺乳動(dòng)物腺細(xì)胞專一性啟動(dòng)子，如α-酪蛋白啟動(dòng)子、β-酪蛋白啟動(dòng)子、β-乳球蛋白啟動(dòng)子和乳清酸性蛋白啟動(dòng)子是優(yōu)選的。
用植物個(gè)體生產(chǎn)本發(fā)明多肽的方法包括培養(yǎng)按照以下文獻(xiàn)中所披露的已知方法導(dǎo)入編碼本發(fā)明多肽的基因所獲得的轉(zhuǎn)基因植物的方法，以便在植物體內(nèi)產(chǎn)生并積累所述多肽組織培養(yǎng)(Soshiki Baiyo)，20，1994；組織培養(yǎng)，21，1995；和生物技術(shù)趨勢(shì)，15，45，1997，然后從所述植物內(nèi)回收所述多肽。
為了分離并純化由本發(fā)明的轉(zhuǎn)化體所產(chǎn)生的所述多肽，可以使用分離和純化酶的常規(guī)方法。
例如，如果本發(fā)明的多肽是以可溶形式在細(xì)胞中表達(dá)的話，在培養(yǎng)結(jié)束之后，通過離心回收所述細(xì)胞，并懸浮在含水緩沖液中，然后用超聲波破碎器、French Press、Manton-Gaulin勻漿器、Dynomill等破碎，以便獲得無細(xì)胞提取物。
通過用于分離并純化酶的一般方法，可以從通過對(duì)所述無細(xì)胞提取物進(jìn)行離心而獲得的上清液中獲得純化產(chǎn)物，例如，溶劑萃取、用硫酸銨等進(jìn)行鹽析、脫鹽、用有機(jī)溶劑進(jìn)行沉淀、用諸如二乙基氨基乙基(DEAE)-Sepharose、DIAION FPR-75(由Mitsubishi化學(xué)公司生產(chǎn))等的樹脂進(jìn)行的陰離子交換層析，用S-Sepharose FF(由Pharmacia生產(chǎn))等的樹脂進(jìn)行陽離子交換層析，用諸如丁基Sepharose、丙基Sepharose等的樹脂進(jìn)行疏水性親和層析，用分子篩進(jìn)行凝膠過濾、親和層析、層析聚焦、或電泳，如等電聚焦等，以上方法單獨(dú)使用或組合使用。
當(dāng)所述蛋白是以包含體的形式在宿主細(xì)胞中表達(dá)時(shí)，用相同方法收集宿主細(xì)胞，破碎并離心，以便以沉淀級(jí)份的形式回收所述蛋白的包含體。然后，用一種蛋白變性劑溶解所述蛋白包含體。
用不含有蛋白變性劑的溶液或含有較低濃度的不會(huì)使所述蛋白發(fā)生變性的蛋白變性劑的溶液稀釋或透析所述溶解的蛋白溶液。因此，重建所述蛋白的正常三級(jí)結(jié)構(gòu)。在所述方法之后，可以通過類似于上文所述的純化或分離方法獲得所述蛋白的純化產(chǎn)物。
當(dāng)本發(fā)明的蛋白或其糖基化衍生物被從細(xì)胞中外泌時(shí)，可以從培養(yǎng)上清液中收集所述蛋白或其衍生物。就是說，以與上文所述離心相似的方法處理所述培養(yǎng)物獲得所述培養(yǎng)上清液。然后，可以用類似于上文所述的純化和分離方法從所述上清液中獲得純化產(chǎn)物。
由此獲得的蛋白的例子包括含有SEQ ID NO1所示氨基酸序列的蛋白。
另外，可以生產(chǎn)本發(fā)明蛋白和其他蛋白的融合蛋白，并用對(duì)所述融合蛋白有親和力的物質(zhì)通過親和層析純化。例如，可以按照披露于以下文獻(xiàn)中的方法以與蛋白A的融合蛋白形式生產(chǎn)本發(fā)明的蛋白Lowe等(美國科學(xué)院院報(bào)86，8227，1989；基因發(fā)育，41288，1990)，或日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?36963/93或823021/94，并用免疫球蛋白G通過親和層析純化。
另外，本發(fā)明的蛋白可以與Flag肽的融合蛋白形式生產(chǎn)，并可以用抗-Flag抗體通過親和層析純化所述融合蛋白(美國科學(xué)院院報(bào)86，8227，1989；基因發(fā)育，41288，1990)?？梢允褂每顾龅鞍妆旧淼目贵w，通過親和層析進(jìn)一步純化。
另外，根據(jù)由此所獲得的蛋白的信息，可以通過化學(xué)合成方法生產(chǎn)本發(fā)明蛋白，如Fmoc(芴甲氧基羰基)方法，tBoc(t-丁氧基羰基)方法等。還可以用由Advanced ChemTech、pERKIN-Elmer、Pharmacia、Protein Technology Instrument、Synthecell-Vega、PerSeptive、Shimadzu公司等所生產(chǎn)的肽合成儀進(jìn)行化學(xué)合成。
3.生產(chǎn)除蟲菌素糖苷配基或除蟲菌素除蟲菌素糖苷配基可以這樣生產(chǎn)在一種培養(yǎng)基中培養(yǎng)按上述第2節(jié)所制備的、具有除蟲菌素糖苷配基合成酶基因或其組件或亞組件的轉(zhuǎn)化體，以便在該培養(yǎng)基中生產(chǎn)并積累除蟲菌素糖苷配基，然后從該培養(yǎng)基中回收除蟲菌素糖苷配基。
當(dāng)用于制備轉(zhuǎn)化體的宿主能夠產(chǎn)生除蟲菌素時(shí)，可以在通過以上所述宿主中導(dǎo)入除蟲菌素糖苷配基合成酶基因或其組件或亞組件而獲得的轉(zhuǎn)化體的任一種中有效生產(chǎn)除蟲菌素糖苷配基或除蟲菌素。由此所獲得的轉(zhuǎn)化體能以高于該宿主的效率生產(chǎn)除蟲菌素糖苷配基或除蟲菌素。
當(dāng)用于制備轉(zhuǎn)化體的宿主不能產(chǎn)生除蟲菌素時(shí)，將除蟲菌素糖苷配基合成酶基因?qū)朐撍拗?，以便獲得能夠產(chǎn)生除蟲菌素糖苷配基的轉(zhuǎn)化體。
在生產(chǎn)除蟲菌素或除蟲菌素糖苷配基時(shí)，可以按照披露于第2節(jié)中的培養(yǎng)方法培養(yǎng)上述轉(zhuǎn)化體。
一種已知的除蟲菌素是一種具有16員環(huán)的大環(huán)內(nèi)酯，有2個(gè)糖殘基通過糖苷鍵連接在它上面?？梢酝ㄟ^本領(lǐng)域所熟知的方法將除蟲菌素糖苷配基轉(zhuǎn)化成除蟲菌素，例如，通過披露于細(xì)菌學(xué)雜志(175，2552-2563，1993)中的方法對(duì)除蟲菌素糖苷配基進(jìn)行糖基化。
4.生產(chǎn)修飾過的除蟲菌素糖苷配基或除蟲菌素除蟲菌素糖苷配基是通過由除蟲菌素糖苷配基合成酶通過延伸低級(jí)脂肪酸單位而形成的(在除了起始反應(yīng)以外的其他反應(yīng)中以二羧酸的CoA酯的形式使用)，即縮合以便得到聚酮化合物碳鏈，并在縮合期間修飾所產(chǎn)生的β-羰基基團(tuán)。如上文所述，除蟲菌素糖苷配基合成酶基因是由組件組成，每一個(gè)組件包括編碼除蟲菌素糖苷配基合成酶功能域的DNA(亞組件)。
亞組件編碼參與在聚酮化合物合成期間縮合的ACP、KS和AT，并且編碼參與β-羰基基團(tuán)修飾的KR、DH或ER。
因此，根據(jù)在上述第一節(jié)中所測(cè)定的有關(guān)除蟲菌素糖苷配基合成酶基因核苷酸信息，可以通過修飾一個(gè)亞組件在所述縮合過程中改變糖苷配基部分的碳鏈長度和β-碳原子上官能團(tuán)的類型。
另外，通過使一個(gè)亞組件選擇性地失活，可以導(dǎo)致具有可預(yù)測(cè)的新型除蟲菌素或其特定成分的產(chǎn)生。
舉例來說，通過取代所述除蟲菌素糖苷配基合成酶基因上的亞組件DH2片段或?qū)⑵滢D(zhuǎn)化成不具有脫水酶活性的無活性形式，可以將能產(chǎn)生除蟲菌素B1A和B2A的除蟲鏈霉菌K2038菌株轉(zhuǎn)化成僅能產(chǎn)生除蟲菌素B2A的菌株。
所述亞組件DH2片段可以用其無活性形式取代，或?qū)⑵滢D(zhuǎn)化成無活性形式，例如，通過根據(jù)披露于分子克隆，第2版中的一般方法讓上述菌株的亞組件DH2進(jìn)行同源重組，得到SEQ ID NO7所示的核苷酸序列。
因此所獲得的、能夠產(chǎn)生修飾過的(或改變了的除蟲菌素糖苷配基的菌株，可被用于按照生產(chǎn)除蟲菌素的一般方法生產(chǎn)并獲得修飾過的除蟲菌素糖苷配基或修飾過的除蟲菌素糖。
實(shí)施本發(fā)明的最佳方式提供下面的實(shí)施例只是出于說明目的，而不是要限定上文明確限定本發(fā)明的范圍。例1測(cè)定除蟲鏈霉菌的除蟲菌素糖苷配基合成酶基因的核苷酸序列按以下方法測(cè)定源于除蟲鏈霉菌的、編碼除蟲菌素糖苷配基合成酶的DNA的核苷酸序列(US5206155，F(xiàn)ERM BP-2773)。
從含有與編碼除蟲菌素B5-O-轉(zhuǎn)甲基酶的基因(AveD；基因，206，175-180，1998)共同分離的除蟲菌素糖苷配基合成酶基因(AveAI和AveAII)的片段的質(zhì)粒中亞克隆所述除蟲菌素糖苷配基合成酶基因上的連續(xù)的或重疊的DNA片段。然后測(cè)定該亞克隆中插入的DNA片段的核苷酸序列。
更具體地講，AveAI和AveAII的完整核苷酸序列可以通過以下方法測(cè)定亞克隆存在于
圖1所示AveAI和AveAII的BamHI限制圖譜上的3.4kbp、2.0kbp、0.5kbp、6.8kbp、7.0kbp、7.8kbp、3.7kbp、4.8kbp、1.3kbp、2.4kbp、0.7kbp、1.0kbp、5.4kbp、2.5kbp、1.9kbp、0.1kbp、7.0kbp、3.1kbp、4.7kbp和1.3kbp的BamHI處理過的片段；用外切核酸酶III和S1核酸酶處理上述亞克隆中的插入DNA片段，以便制備一系列缺失片段；然后用熒光標(biāo)記的引物進(jìn)行循環(huán)測(cè)序反應(yīng)，以便測(cè)定每一個(gè)缺失片段的核苷酸序列?；駻veAI和AveAII分別具有SEQ IDNO1和SEQ ID NO2所示的核苷酸序列。例2通過對(duì)組件2上的脫水酶功能域進(jìn)行核苷酸修飾單獨(dú)生產(chǎn)除蟲菌素B2a除蟲鏈霉菌K2033(FERM BP-2775)能產(chǎn)生除蟲菌素B1a和除蟲菌素B2a。
在例1中獲得并測(cè)序的源于所述產(chǎn)除蟲菌素菌株的除蟲菌素糖苷配基合成酶基因的信息(SEQ ID NO1和2)表明，除蟲菌素是通過圖2所示生物合成途徑生物合成的。
除蟲菌素B1a與除蟲菌素B2a的不同之處僅在于除蟲菌素B1a在其糖苷配基部分上的22-和33-位置之間具有一個(gè)雙鍵，而除蟲菌素B2a在糖苷配基部分上的22-和33-位置之間具有一個(gè)單鍵，并且在23-位置上有一個(gè)羥基基團(tuán)。
上面所發(fā)現(xiàn)的除蟲菌素生物合成途徑表明，SU2(DH2)的除蟲菌素糖苷配基合成酶功能域DH決定除蟲菌素B1a的糖苷配基部分的22-和23-位置之間的雙鍵的形式，而SU10(DH10)的除蟲菌素糖苷配基合成酶功能域DH不具有脫水酶活性。
根據(jù)通過將DH2轉(zhuǎn)化成象DH10那樣的不具有脫水酶活性的功能域可以獲得僅能產(chǎn)生除蟲菌素B2a的菌株這一構(gòu)思，按以下方法制備了不具有脫水酶活性的DH2。
在例1中獲得的除蟲菌素糖苷配基合成酶基因具有6個(gè)DH功能域DH2、DH6、DH9、DH10、DH11和DH12。比較上述功能域的核苷酸序列發(fā)現(xiàn)，DH10在脫水酶所共有的共有序列上明顯不同于其他DH功能域。
更具體地講，發(fā)現(xiàn)直接參與除蟲菌素糖苷配基形成的DH2、DH6、DH9、DH11和DH12氨基酸序列包括共有序列HXaaXaaXaaGXaaXaaXaaXaaP(SEQ ID NO13)或HXaaXaaXaaGXaaXaaXaaXaaS(SEQ ID NO14)，其中，H、G、P、S和Xaa分別表示組氨酸、甘氨酸、脯氨酸、絲氨酸和任何氨基酸；而DH10的相應(yīng)序列為YxaaXaaXaaGXaaXaaXaaXaaS(SEQ ID NO15)，其中，Y表示酪氨酸，而Xaa、G和S的定義如上文所述。
因此，用Y(Tyr)取代N-末端H(His)被認(rèn)為能產(chǎn)生沒有活性的脫水酶。
構(gòu)建一種DNA，它所具有的核苷酸序列編碼這樣的序列用DH10的相應(yīng)序列-Tyr-Glu-(SEQ ID NO6中的氨基酸1008-1017)取代了DH2的共有序列[-His-Ala-Val-Gly-Gly-Thr-Val-Leu-Leu-Ser-(SEQID NO16)，SEQ ID NO3中的氨基酸3037-3046]上的N-末端氨基酸序列-His-Ala-。就是說，按以下方法用序列5’-TAC-GAG-3’取代了DH2功能域的DNA序列5’-CAT-GCC-3’(SEQ ID NO1上的核苷酸9109-9114)。
用限制酶SmaI消化含有DH2功能域的aveAI片段的DNA片段，并將相當(dāng)于SEQ ID NO1上的核苷酸的7869-10196的2327bp的SmaI片段亞克隆到載體質(zhì)粒pUC19的SmaI位點(diǎn)上。
將Taq DNA聚合酶緩沖液，dATP、dCTP、dTTP和Taq聚合酶添加到所得到的重組質(zhì)粒中，然后將其分成兩等份。
向上述一份等份試樣中添加SEQ ID NO9所示核苷酸序列的引物(相當(dāng)于SEQ ID NO1中的核苷酸9098-9127)和具有SEQ ID NO10所示核苷酸序列的反義引物(相當(dāng)于SEQ ID NO1中核苷酸9193-9222的反義序列)。
向另一份等份試樣中添加具有SEQ ID NO11所示核苷酸序列的反義引物(相當(dāng)于SEQ ID NO1的核苷酸9098-9127的反義序列)和具有SEQ ID NO12所示核苷酸序列的引物(相當(dāng)于SEQ ID NO1的核苷酸8948-8977)。
在上述添加之后，在96℃下處理每一個(gè)等份試樣5分鐘，然后在以下條件下重復(fù)所述反應(yīng)5-10輪每一輪98℃ 15秒，68℃ 30秒。
在所述反應(yīng)之后，向每一個(gè)等份試樣添加外切核酸酶I和堿性磷酸酶，在37℃培養(yǎng)15分鐘，然后在80℃下處理10分鐘，使這兩種酶失活。
在使以上兩種酶失活之后，向每一種反應(yīng)溶液中添加Taq DNA聚合酶緩沖液，dATP、dGTP、dCTP、dTTP，具有SEQ ID NO12的核苷酸序列的引物(相當(dāng)于SEQ ID NO1的核苷酸8948-8977)，具有SEQ ID NO10的核苷酸序列的反義引物(相當(dāng)于SEQ ID NO1的核苷酸9193-9222的反義序列)和Taq DNA聚合酶。在96℃下處理每一種反應(yīng)溶液5分鐘，并在以下條件下重復(fù)所述反應(yīng)25輪每一輪為98℃ 15秒，68℃ 30秒。
在所述反應(yīng)之后，向每一個(gè)等份試樣添加外切核酸酶I和堿性磷酸酶，在37℃培養(yǎng)15分鐘，然后在80℃下處理10分鐘，使這兩種酶失活。
在所述酶失活之后，將限制酶XcmI和BsaAI添加到每一種反應(yīng)溶液中，以便獲得XcmI-BsaAI處理過的DNA片段。
將限制酶XcmI和BsaAI添加到具有插入的2327bp SmaI片段的上面制備的重組質(zhì)粒中，以便獲得XcmI-BsaAI處理過的載體片段。將XcmI-BsaAI處理過的載體片段\T4 DNA連接酶緩沖液、ATP和T4 DNA連接酶添加到XcmI-BsaAI處理過的DNA片段，然后在22℃下培養(yǎng)過夜，以便將這些片段連接在一起，從而獲得具有插入的XcmI-BsaAI處理的DNA片段的質(zhì)粒。
在用所述質(zhì)粒轉(zhuǎn)化大腸桿菌細(xì)胞之后，從單菌落中提取所述重組質(zhì)粒，并證實(shí)插入所述載體中的每一種DNA片段的核苷酸序列，從而篩選具有導(dǎo)入了想要的核苷酸取代的片段的克隆。
從所選擇的克隆中提取所述插入的DNA片段，然后按照披露于日本公開的未經(jīng)審查的專利申請(qǐng)?zhí)?44605/92中的方法通過同源重組與除蟲鏈霉菌K2038的染色體上的DH2片段進(jìn)行重組。
在一般除蟲菌素生產(chǎn)的條件下培養(yǎng)所得到的重組除蟲菌素鏈霉菌K2210，然后用甲醇提取所得到的細(xì)胞。
用下面所提供的兩種方法分析所得到的提取物。
(1)在硅凝膠上使用薄層層析的方法層析條件硅凝膠Merck硅凝膠板F254(Merk公司)展開液 正己烷/異丙醇＝85/15檢測(cè)UV(2)使用高效液相層析的方法層析條件柱，ODS-Sypersil-3(Elmer公司)移動(dòng)相 乙腈/甲醇/水＝60/14/26流速0.6毫升/分鐘檢測(cè)246納米溫度室溫在這兩種分析方法中，僅觀察到了與除蟲菌素B2a相同的峰。另外，通過在Sephadex LH-20和硅凝膠上層析純化所述培養(yǎng)提取物，以便得到純化產(chǎn)物。通過MR和質(zhì)譜法分析純化的產(chǎn)物，表明上述重組菌株只能產(chǎn)生除蟲菌素B2a。
就是說，按照上述方法可以單獨(dú)生產(chǎn)并獲得除蟲菌素B2a。工業(yè)應(yīng)用本發(fā)明可以提供編碼參與除蟲菌素生物合成的多功能酶的DNA，可將其用作藥物制劑、獸醫(yī)制劑和農(nóng)藥；由所述DNA所編碼的多肽；包括所述DNA的載體；用所述DNA或載體轉(zhuǎn)化過的宿主細(xì)胞；和生產(chǎn)除蟲菌素和修飾過的除蟲菌素的方法。
序列表獨(dú)立文本-SEQ ID NO9表示基于SEQ ID NO1的核苷酸9098-9127之間的序列的引物SEQ ID NO10表示基于SEQ ID NO1的核苷酸9193-9222之間的序列的反義引物SEQ ID NO11表示基于SEQ ID NO1的核苷酸9098-9127之間的序列的引物SEQ ID NO12表示基于SEQ ID NO1的核苷酸8948-8977之間的序列的引物本發(fā)明的范圍是由所附權(quán)利要求書限定的，并且可以理解的是，在不脫離本發(fā)明構(gòu)思和范圍的前提下，可以對(duì)其作出其他多種改變和改進(jìn)。因此，上述實(shí)施例被理解為在各方面都是說明性的，而不是限定性的。另外，權(quán)利要求書的等同內(nèi)容也屬于本發(fā)明的范圍。
在本說明書中所引用的所有專利、專利申請(qǐng)和其他文獻(xiàn)和在本說明書中所披露的內(nèi)容和/或日本專利申請(qǐng)?zhí)?46961/99(它是本申請(qǐng)的優(yōu)先權(quán)文件)的附圖被以其全文形式收作本文參考。
序列表<110>The Kitasato Institute<120>除蟲菌素糖苷配基合成酶基因<130>PH-775-PCT<140><141><150>JP99/46961<151>24-FEB-1999<160>16<170>PatentIn Ver.2.0<210>1<211>30692<212>DNA<213>除蟲鏈霉菌<220><221>CDS<222>(1)..(11916)<220><221>CDS<222>(11971)..(30687)<400>1gtg cag agg atg gac ggc ggg gaa gaa ccc cgc cct gcg gca ggg gag 48Val Gln Arg Met Asp Gly Gly Glu Glu Pro Arg Pro Ala Ala Gly Glu1 5 10 15gtc ctc gga gtg gcc gac gag gcg gac ggc ggc gtc gtc ttc gtt ttt 96Val Leu Gly Val Ala Asp Glu Ala Asp Gly Gly Val Val Phe Val Phe20 25 30ccc ggg cag ggc ccg caa tgg ccg ggc atg gga agg gaa ctt ctc gac 144Pro Gly Gln Gly Pro Gln Trp Pro Gly Met Gly Arg Glu Leu Leu Asp35 40 45gct tcc gac gtc ttc cgg gag agc gtc cgc gcc tgc gaa gcc gcg ttc 192Ala Ser Asp Val Phe Arg Glu Ser Val Arg Ala Cys Glu Ala Ala Phe50 55 60gcg ccc tac gtc gac tgg tcg gtg gag cag gtg ttg cgg gac tcg ccg 240Ala Pro Tyr Val Asp Trp Ser Val Glu Gln Val Leu Arg Asp Ser Pro65 70 75 80gac gct ccc ggg ctg gac cgg gtg gac gtc gtc cag ccg acc ctg ttc 288Asp Ala Pro Gly Leu Asp Arg Val Asp Val Val Gln Pro Thr Leu Phe85 90 95gcc gtc atg atc tcc ctg gcc gcc ctc tgg cgc tcg caa ggg gtc gag 336Ala Val Met Ile Ser Leu Ala Ala Leu Trp Arg Ser Gln Gly Val Glu100 105 110ccg tgc gcg gtg ctg gga cac agc ctg ggc gag atc gcg gca gcc cac 384Pro Cys Ala Val Leu Gly His Ser Leu Gly Glu Ile Ala Ala Ala His115 120 125gtc tcg gga ggc ctg tcc ctg gcc gac gcc gca cgc gtg gtg acg ctt 432Val Ser Gly Gly Leu Ser Leu Ala Asp Ala Ala Arg Val Val Thr Leu130 135 140tgg agc cag gca cag acc acc ctt gcc ggg acc ggc gcg ctc gtc tcc 480Trp Ser Gln Ala Gln Thr Thr Leu Ala Gly Thr Gly Ala Leu Val Ser145 150 155 160gtc gcc gcc acg ccg gat gag ctc ctg ccc cga atc gct ccg tgg acc 528Val Ala Ala Thr Pro Asp Glu Leu Leu Pro Arg Ile Ala Pro Trp Thr165 170 175gag gac aac ccg gcg cgg ctc gcc gtc gca gcc gtc aac gga ccc cgg 576Glu Asp Asn Pro Ala Arg Leu Ala Val Ala Ala Val Asn Gly Pro Arg180 185 190agc aca gtc gtt tcc ggt gcc cgc gag gcc gtc gcg gac ctg gtg gcc 624Ser Thr Val Val Ser Gly Ala Arg Glu Ala Val Ala Asp Leu Val Ala195 200 205gac ctc acc gcc gcg cag gtg cgc acg cgc atg atc ccg gtg gac gtt 672Asp Leu Thr Ala Ala Gln Val Arg Thr Arg Met Ile Pro Val Asp Val210 215 220ccc gcc cac tcc ccc ctg atg tac gcc atc gag gaa cgg gtc gtc agc 720Pro Ala His Ser Pro Leu Met Tyr Ala Ile Glu Glu Arg Val Val Ser225 230 235 240ggc ctg ctg ccc atc acc cca cgc ccc tcc cgc atc ccc ttc cac tcc 768Gly Leu Leu Pro Ile Thr Pro Arg Pro Ser Arg Ile Pro Phe His Ser245 250 255tcg gtg acc ggc ggc cgc ctc gac acc cgc gag cta gac gcg gcg tac 816Ser Val Thr Gly Gly Arg Leu Asp Thr Arg Glu Leu Asp Ala Ala Tyr260 265 270tgg tac cgc aac atg tcg agc acg gtc cgg ttc gag ccc gcc gcc cgg 864Trp Tyr Arg Asn Met Ser Ser Thr Val Arg Phe Glu Pro Ala Ala Arg275 280 285ctg ctt ctg cag cag ggg ccc aag acg ttc gtc gag atg agc ccg cac 912Leu Leu Leu Gln Gln Gly Pro Lys Thr Phe Val Glu Met Ser Pro His290 295 300ccg gtg ctg acc atg ggc ctc cag gag ctc gcc ccg gac ctg ggc gac 960Pro Val Leu Thr Met Gly Leu Gln Glu Leu Ala Pro Asp Leu Gly Asp305 310 315 320acc acc ggc acc gcc gac acc gtg atc atg ggc acg ctg cgc cgc ggc 1008Thr Thr Gly Thr Ala Asp Thr Val Ile Met Gly Thr Leu Arg Arg Gly325 330 335cag ggc acc ctg gac cac ttc ctg acg tct ctc gcc caa cta cgg ggg 1056Gln Gly Thr Leu Asp His Phe Leu Thr Ser Leu Ala Gln Leu Arg Gly340 345 350cat ggt gag acg tcg gcg acc acc gtc ctc tcg gca cgc ctg acc gcg 1104His Gly Glu Thr Ser Ala Thr Thr Val Leu Ser Ala Arg Leu Thr Ala355 360 365ctg tcc ccc acg cag cag cag tcg ctg ctc ctg gac ctg gtg cgc gcc 1152Leu Ser Pro Thr Gln Gln Gln Ser Leu Leu Leu Asp Leu Val Arg Ala370 375 380cac acc atg gcg gtg ctg aac gac gac gga aac gag cgc acc gcg tcg 1200His Thr Met Ala Val Leu Asn Asp Asp Gly Asn Glu Arg Thr Ala Ser385 390 395 400gat gcc ggc cca tcg gcg agt ttc gcc cac ctc ggc ttc gac tcc gtc 1248Asp Ala Gly Pro Ser Ala Ser Phe Ala His Leu Gly Phe Asp Ser Val405 410 415atg ggt gtc gaa ctg cgc aac cgc ctc agc aag gcc acg ggc ctg cgg 1296Met Gly Val Glu Leu Arg Asn Arg Leu Ser Lys Ala Thr Gly Leu Arg420 425 430ttg ccc gtg acg ctc atc ttc gac cac acc acg ccg gcc gcg gtc gcc 1344Leu Pro Val Thr Leu Ile Phe Asp His Thr Thr Pro Ala Ala Val Ala435 440 445gcg cgc ctt cgg acc gcg gcg ctc ggc cac ctc gac gag gac acc gcg 1392Ala Arg Leu Arg Thr Ala Ala Leu Gly His Leu Asp Glu Asp Thr Ala450 455 460ccc gta ccg gac tca ccc agc ggc cac gga ggc acg gca gcg gcg gac 1440Pro Val Pro Asp Ser Pro Ser Gly His Gly Gly Thr Ala Ala Ala Asp465 470 475 480gac ccg atc gcc atc atc ggc atg gca tgc cgt ttc ccg ggc gga gtc 1488Asp Pro Ile Ala Ile Ile Gly Met Ala Cys Arg Phe Pro Gly Gly Val485 490 495cgg tcc ccg aag gac ctg tgg gag ctg gcc gcc tcg ggc gga gac gcc 1536Arg Ser Pro Lys Asp Leu Trp Glu Leu Ala Ala Ser Gly Gly Asp Ala500 505 510atc ggg ccg ttc ccc acc gac cgc gga tgg ccc acg gaa cag cgt cac 1584Ile Gly Pro Phe Pro Thr Asp Arg Gly Trp Pro Thr Glu Gln Arg His515 520 525gcc cag gac ccc acg cag ccc ggc acg ttc tat ccg cag gga ggc ggg 1632Ala Gln Asp Pro Thr Gln Pro Gly Thr Phe Tyr Pro Gln Gly Gly Gly530 535 540ttc ctt cac gac gcg gcg cac ttc gac gcc ggc ttc ttc gga atc agt 1680Phe Leu His Asp Ala Ala His Phe Asp Ala Gly Phe Phe Gly Ile Ser545 550 555 560cca cgt gag gca ctg gcg atg gat ccg cag cag cgg ctg ctg ctg gag 1728Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu565 570 575acg tcc tgg gag gcg ttc gag cgg gcg gga atc gat ccg ctg tcg gta 1776Thr Ser Trp Glu Ala Phe Glu Arg Ala Gly Ile Asp Pro Leu Ser Val580 585 590cgc ggg tcc cgt acg ggc gtc ttc gcg ggc gcc ctc tcc ttc gac tac 1824Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Ala Leu Ser Phe Asp Tyr595 600 605ggc ccg cgt atg gac acc gcg tcg tcg gag ggc gcc gcg gac gtg gag 1872Gly Pro Arg Met Asp Thr Ala Ser Ser Glu Gly Ala Ala Asp Val Glu610 615 620ggc cac atc ctc acc ggt acc acg ggc agc gtc ctg tcg ggc cgt atc 1920Gly His Ile Leu Thr Gly Thr Thr Gly Ser Val Leu Ser Gly Arg Ile625 630 635 640gcc tac agc ttc ggg ctg gaa ggg ccg gcg atc acc gtg gac acg ggg 1968Ala Tyr Ser Phe Gly Leu Glu Gly Pro Ala Ile Thr Val Asp Thr Gly645 650 655tgc tcg gca tcg ctc gtg acg ctg cat ctg gcg tgc cag tcg ctg cgg 2016Cys Ser Ala Ser Leu Val Thr Leu His Leu Ala Cys Gln Ser Leu Arg660 665 670tcg ggt gag tgc acg ctc gcg ctg gcc ggc ggc gtc tcg gtc atg tcc 2064Ser Gly Glu Cys Thr Leu Ala Leu Ala Gly Gly Val Ser Val Met Ser675 680 685acc ctc ggc atg ttc atc gag ttc tcc cgg cag cgc ggg ctg tcg gtg 2112Thr Leu Gly Met Phe Ile Glu Phe Ser Arg Gln Arg Gly Leu Ser Val690 695 700gac ggc agg tgc aag gcg tac tcg gct gca gcc gac ggc acc ggc tgg 2160Asp Gly Arg Cys Lys Ala Tyr Ser Ala Ala Ala Asp Gly Thr Gly Trp705 710 715 720ggc gag ggc gtc ggg atg ctg ttg gtg gag cgg ttg tcg gat gcg gtg 2208Gly Glu Gly Val Gly Met Leu Leu Val Glu Arg Leu Ser Asp Ala Val725 730 735cgg ctg ggg cat cgg gtg ctg gcg gtg gta cgc ggc agt gcg gtc aac 2256Arg Leu Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn740 745 750cag gac ggt gcg tcg aat ggg ctg acg gcg ccg aac ggt ccg gct cag 2304Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ala Gln755 760 765gag cgg gtg atc cgg cag gcg ttg gcg aac gcg ggg ttg tcc gtg gcg 2352Glu Arg Val Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Ser Val Ala770 775 780gat gtg gat gtg gtg gag ggg cac ggg acg ggc acg acg ctg ggt gat 2400Asp Val Asp Val Val Glu Gly His Gly Thr Gly Thr Thr Leu Gly Asp785 790 795 800ccg atc gag gca cag gcg ttg ctc gcc acg tac ggg cag cgg gcc ggt 2448Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Arg Ala Gly805 810 815gac agg ccg ctg tgg ctg ggg tct ctg aag tcc aac atc ggg cac acc 2496Asp Arg Pro Leu Trp Leu Gly Ser Leu Lys Ser Asn Ile Gly His Thr820 825 830atg gct gcc gcg ggt gtg ggt ggg gtc atc aag atg gtg atg gcg ttg 2544Met Ala Ala Ala Gly Val Gly Gly Val Ile Lys Met Val Met Ala Leu835 840 845cgg gag ggg gtg ttg ccg cgg acg ttg cat gtg gat aag ccg tcg ccg 2592Arg Glu Gly Val Leu Pro Arg Thr Leu His Val Asp Lys Pro Ser Pro850 855 860cag gtg gac tgg tcc gcg ggg gcg gtg cgg ctg ctg acg gag gcg gtg 2640Gln Val Asp Trp Ser Ala Gly Ala Val Arg Leu Leu Thr Glu Ala Val865 870 875 880ccg tgg ccg ggg gac gcg gca ggg cgg ttg cgg cgg gcg gga gtg tcg 2688Pro Trp Pro Gly Asp Ala Ala Gly Arg Leu Arg Arg Ala Gly Val Ser885 890 895tcg ttc ggg atc ggc ggc acg aat gcg cat gtg att ttg gag gag gcg 2736Ser Phe Gly Ile Gly Gly Thr Asn Ala His Val Ile Leu Glu Glu Ala900 905 910ccg gcg gcg ggg ggc tgt gtt gcc ggg ggt ggg gtg ttg gag ggt gct 2784Pro Ala Ala Gly Gly Cys Val Ala Gly Gly Gly Val Leu Glu Gly Ala915 920 925ccg ggt ctt gcc att tcg gtg gct gag tcg gtg gcc gct cca gtg gct 2832Pro Gly Leu Ala Ile Ser Val Ala Glu Ser Val Ala Ala Pro Val Ala930 935 940gtg tct gcg ccg gtg gct gag tcg gtg ccg gtg ccg gtg ccg gtg ccg 2880Val Ser Ala Pro Val Ala Glu Ser Val Pro Val Pro Val Pro Val Pro945 950 955 960gtt cct gtg ccg gtg tcg gct agg tct gag gct ggg ttg cgg gcg cag 2928Val Pro Val Pro Val Ser Ala Arg Ser Glu Ala Gly Leu Arg Ala Gln965 970 975gcg gag gcg ttg cgt cag tac gtg gca gtc cgg ccg gac gtt tcg ctt 2976Ala Glu Ala Leu Arg Gln Tyr Val Ala Val Arg Pro Asp Val Ser Leu980 985 990gcc gat gtg ggt gcg ggt ctg gcc tgt ggg cgg gct gtg ctg gag cat 3024Ala Asp Val Gly Ala Gly Leu Ala Cys Gly Arg Ala Val Leu Glu His99510001005cgt gcg gtc gtc ctg gcc gcg gac cgt gag gag ctg gtg caa ggg ttg 3072Arg Ala Val Val Leu Ala Ala Asp Arg Glu Glu Leu Val Gln Gly Leu101010151020ggg gcg ctg gcg gcg ggt gag ccg gat cgg cgg gtg acc acg ggt cat 3120Gly Ala Leu Ala Ala Gly Glu Pro Asp Arg Arg Val Thr Thr Gly His1025 103010351040gcg ccg ggt ggt gac cgg ggc ggt gtc gtc ttc gtg ttt ccc gga cag 3168Ala Pro Gly Gly Asp Arg Gly Gly Val Val Phe Val Phe Pro Gly Gln104510501055ggt ggg cag tgg gcc ggg atg ggt gtg cgt ctg ctc gcc tcc tct ccg 3216Gly Gly Gln Trp Ala Gly Met Gly Val Arg Leu Leu Ala Ser Ser Pro106010651070gtg ttc gcc cgg cgg atg cag gcg tgc gag gag gct ctg gcg ccg tgg 3264Val Phe Ala Arg Arg Met Gln Ala Cys Glu Glu Ala Leu Ala Pro Trp107510801085gtg gac tgg tct gtg gtg gac atc ctg cgc cgg gac gcg ggg gat gcg 3312Val Asp Trp Ser Val Val Asp Ile Leu Arg Arg Asp Ala Gly Asp Ala109010951100gtg tgg gag cgg gcc gat gtg gtc cag cct gtg ctg ttc agc gtc atg 3360Val Trp Glu Arg Ala Asp Val Val Gln Pro Val Leu Phe Ser Val Met1105 111011151120gtg tct ttg gct gct ctg tgg cgt tcc tac ggt atc gaa ccc gac gcg 3408Val Ser Leu Ala Ala Leu Trp Arg Ser Tyr Gly Ile Glu Pro Asp Ala112511301135gtc ctt ggc cat tcc cag ggc gag atc gcg gcc gcg cat gtg tgt ggg 3456Val Leu Gly His Ser Gln Gly Glu Ile Ala Ala Ala His Val Cys Gly114011451150gcg ctg agc ctg aag gac gcg gcg aag act gtt gcg ctg cgc agc cgg 3504Ala Leu Ser Leu Lys Asp Ala Ala Lys Thr Val Ala Leu Arg Ser Arg115511601165gcg ctg gcc gct gtg cgg ggc cgg ggc ggc atg gcc tca gtg ccg ctg 3552Ala Leu Ala Ala Val Arg Gly Arg Gly Gly Met Ala Ser Val Pro Leu117011751180cct gcc cag gag gtg gag cag ctc att ggt gag cgg tgg gcg ggg cgg 3600Pro Ala Gln Glu Val Glu Gln Leu Ile Gly Glu Arg Trp Ala Gly Arg1185 119011951200ttg tgg gtg gcg gcg gtc aac ggc ccc cgc tcc acc gcc gtc tcg ggg 3648Leu Trp Val Ala Ala Val Asn Gly Pro Arg Ser Thr Ala Val Ser Gly120512101215gat gcc gag gcg gtg gac gag gtg ctg gcg tac tgt gcc ggc acc ggg 3696Asp Ala Glu Ala Val Asp Glu Val Leu Ala Tyr Cys Ala Gly Thr Gly122012251230gtg cgg gcc cgg cgg atc ccg gtc gac tat gcc tcg cac tgc ccc cat 3744Val Arg Ala Arg Arg Ile Pro Val Asp Tyr Ala Ser His Cys Pro His123512401245gtg cag ccc ctg cgg gag gag ttg ctg gag ctg ctg ggg gac atc agc 3792Val Gln Pro Leu Arg Glu Glu Leu Leu Glu Leu Leu Gly Asp Ile Ser125012551260ccg cag ccg tcc ggc gtg ccg ttc ttc tcc acg gtg gag ggc acc tgg 3840Pro Gln Pro Ser Gly Val Pro Phe Phe Ser Thr Val Glu Gly Thr Trp1265 127012751280ctg gac acc aca acc ctg gac gcc gcc tac tgg tac cgc aac ctg cac 3888Leu Asp Thr Thr Thr Leu Asp Ala Ala Tyr Trp Tyr Arg Asn Leu His128512901295cag ccg gtc cgt ttc agc gat gcc gtc cag gcc ctg gcg gat gac gga 3936Gln Pro Val Arg Phe Ser Asp Ala Val Gln Ala Leu Ala Asp Asp Gly130013051310cac cgc gtc ttc gtc gaa gtc agc ccc cac ccc acc ctc gtc ccc gcc 3984His Arg Val Phe Val Glu Val Ser Pro His Pro Thr Leu Val Pro Ala131513201325atc gaa gac acc acc gaa gac acc gcc gaa gac gtc acc gcg atc ggc 4032Ile Glu Asp Thr Thr Glu Asp Thr Ala Glu Asp Val Thr Ala Ile Gly133013351340agc ctc cgc cgc ggc gac aac gac acc cgc cgc ttc ctc acc gcc ctc 4080Ser Leu Arg Arg Gly Asp Asn Asp Thr Arg Arg Phe Leu Thr Ala Leu1345 135013551360gcc cac acc cat acc acc ggc atc ggc aca ccc acc acc tgg cac cac 4128Ala His Thr His Thr Thr Gly Ile Gly Thr Pro Thr Thr Trp His His136513701375cac tac acc cac cac cac acc cac ccc cac ccc cac acg cac ctc gac 4176His Tyr Thr His His His Thr His Pro His Pro His Thr His Leu Asp138013851390ctg ccc acc tac ccc ttc caa cac cag cac tac tgg ctc gag agc tca 4224Leu Pro Thr Tyr Pro Phe Gln His Gln His Tyr Trp Leu Glu Ser Ser139514001405cag ccg ggt gcc gga tcc ggt tcg ggt gcc ggt gcc ggt tcg ggt gcc 4272Gln Pro Gly Ala Gly Ser Gly Ser Gly Ala Gly Ala Gly Ser Gly Ala141014151420ggt tcc ggg cgg gca ggg act gcg ggc ggg acg gca gag gtg gag tcg 4320Gly Ser Gly Arg Ala Gly Thr Ala Gly Gly Thr Ala Glu Val Glu Ser1425 143014351440cgg ttc tgg gac gcg gtg gcc cgc cag gac ctg gaa acg gtc gcg acc 4368Arg Phe Trp Asp Ala Val Ala Arg Gln Asp Leu Glu Thr Val Ala Thr144514501455aca ctc gcc gtg ccc ccc tcc gcc ggc ctg gac acg gtg gtg ccc gca 4416Thr Leu Ala Val Pro Pro Set Ala Gly Leu Asp Thr Val Val Pro Ala146014651470ctc tcc gcc tgg cac cgc cac caa cac gac caa gcc cgc atc aac acc 4464Leu Ser Ala Trp His Arg His Gln His Asp Gln Ala Arg Ile Asn Thr147514801485tgg acc tac cag gaa acc tgg aaa ccc ctc acc ctc ccc acc acc cac 4512Trp Thr Tyr Gln Glu Thr Trp Lys Pro Leu Thr Leu Pro Thr Thr His149014951500caa ccc cac caa acc tgg ctc atc gcc atc ccc gaa acc cag acc cac 4560Gln Pro His Gln Thr Trp Leu Ile Ala Ile Pro Glu Thr Gln Thr His1505 151015151520cac ccc cac atc acc aac atc ctc acc aac ctc cac cac cac ggc atc 4608His Pro His Ile Thr Asn Ile Leu Thr Asn Leu His His His Gly Ile152515301535acc ccc atc ccc ctc acc ctc aac cac acc cac acc aac ccc caa cac 4656Thr Pro Ile Pro Leu Thr Leu Asn His Thr His Thr Asn Pro Gln His154015451550ctc cac cac acc ctc cac cac acc cga caa caa gcc caa aac cac acc 4704Leu His His Thr Leu His His Thr Arg Gln Gln Ala Gln Asn His Thr155515601565acc gga gcc atc acc ggc ctg ctc tcc ctc ctc gcc ctc gac gaa aca 4752Thr Gly Ala Ile Thr Gly Leu Leu Ser Leu Leu Ala Leu Asp Glu Thr157015751580ccc cac ccc cac cac ccc cac aca ccc acc ggc acc ctc ctc aac ctc 4800Pro His Pro His His Pro His Thr Pro Thr Gly Thr Leu Leu Asn Leu1585 159015951600acc ctc acc caa acc cac acc caa acc cac cca cca acc ccc ctc tgg 4848Thr Leu Thr Gln Thr His Thr Gln Thr His Pro Pro Thr Pro Leu Trp160516101615tac gcc acc acc aac gcc acc acc acc cac ccc aac gac ccc ctc aca 4896Tyr Ala Thr Thr Asn Ala Thr Thr Thr His Pro Asn Asp Pro Leu Thr162016251630cac ccc acc caa gcc caa acc tgg gga ctc gcc cgc acc acc ctc ctc 4944His Pro Thr Gln Ala Gln Thr Trp Gly Leu Ala Arg Thr Thr Leu Leu163516401645gaa cac ccc acc cac acc gcc gga atc atc gac ctc ccc acc acc ccc 4992Glu His Pro Thr His Thr Ala Gly Ile Ile Asp Leu Pro Thr Thr Pro165016551660acc ccc cac acc ctc cag cac ctc acc caa acc ctc acc caa ccc cac 5040Thr Pro His Thr Leu Gln His Leu Thr Gln Thr Leu Thr Gln Pro His1665 167016751680cac caa acc caa ctc gcc atc cgc acc acc ggc acc cac acc cgc cgc 5088His Gln Thr Gln Leu Ala Ile Arg Thr Thr Gly Thr His Thr Arg Arg168516901695ctc acc ccc acc acc ctc acc ccc aca cac caa cca ccc acc ccc acc 5136Leu Thr Pro Thr Thr Leu Thr Pro Thr His Gln Pro Pro Thr Pro Thr170017051710ccc cac gga acc acc ctc atc acc ggc gga acc ggc gcc ctc gcc acc 5184Pro His Gly Thr Thr Leu Ile Thr Gly Gly Thr Gly Ala Leu Ala Thr171517201725cac ctc acc cac cac ctc acc acc cac caa ccc acc caa cac ctc ctc 5232His Leu Thr His His Leu Thr Thr His Gln Pro Thr Gln His Leu Leu173017351740ctc acc agc cga acc ggc ccc cac acc ccc cac gca caa cac ctc acc 5280Leu Thr Ser Arg Thr Gly Pro His Thr Pro His Ala Gln His Leu Thr1745 175017551760acc caa ctc caa caa aaa ggc atc cac ctc acc atc acc acc tgc gac 5328Thr Gln Leu Gln Gln Lys Gly Ile His Leu Thr Ile Thr Thr Cys Asp176517701775acc agc aac cca gac caa ctc caa caa ctc ctc aac acc atc ccc cca 5376Thr Ser Asn Pro Asp Gln Leu Gln Gln Leu Leu Asn Thr Ile Pro Pro178017851790caa cac ccc ctc acc acc gtc atc cac acc gca ggc atc ctc gac gac 5424Gln His Pro Leu Thr Thr Val Ile His Thr Ala Gly Ile Leu Asp Asp179518001805gcc acc ctc acc aac ctc acc ccc acc caa ctc aac aac gtc ctc cgc 5472Ala Thr Leu Thr Asn Leu Thr Pro Thr Gln Leu Asn Asn Val Leu Arg181018151820gcc aaa gcc cac agc gcc cac ctc ctc cac caa ctc acc caa cac acc 5520Ala Lys Ala His Ser Ala His Leu Leu His Gln Leu Thr Gln His Thr1825 183018351840ccc ctc acc gcc ttc gtc ctc tac tcc tcc gcc gcc gcc acc ttc ggc 5568Pro Leu Thr Ala Phe Val Leu Tyr Ser Ser Ala Ala Ala Thr Phe Gly184518501855gca ccc ggc caa gcc aac tac gcc gca gcc aac gcc tac ctc gac gcc 5616Ala Pro Gly Gln Ala Asn Tyr Ala Ala Ala Asn Ala Tyr Leu Asp Ala186018651870ctc gcc cac cac cgc cac acc cac cac ctc ccc gcc acc agc atc gcc 5664Leu Ala His His Arg His Thr His His Leu Pro Ala Thr Ser Ile Ala187518801885tgg ggc acc tgg caa gga aac gga ctc gct gat tcg gac aag gcc cgc 5712Trp Gly Thr Trp Gln Gly Asn Gly Leu Ala Asp Ser Asp Lys Ala Arg189018951900gca tat ctc gac cgc cgc ggg ttt cga ccc atg tca ccc gag ttg gcc 5760Ala Tyr Leu Asp Arg Arg Gly Phe Arg Pro Met Ser Pro Glu Leu Ala1905 191019151920acg gca gcg gtc acg cag gcg atc gcg gac acc gaa cgg ccg tat gtc 5808Thr Ala Ala Val Thr Gln Ala Ile Ala Asp Thr Glu Arg Pro Tyr Val192519301935gtc atc gcc gac atc gac tgg agc aag atc gaa cac acc tct cag acc 5856Val Ile Ala Asp Ile Asp Trp Ser Lys Ile Glu His Thr Ser Gln Thr194019451950agc gac ctg gtg agc gcg gcc cgg gaa agg gag cca gct gtc cag cgc 5904Ser Asp Leu Val Ser Ala Ala Arg Glu Arg Glu Pro Ala Val Gln Arg195519601965ccc act cca ccg gcg gag ttg cac aaa acg ctg gcc cat cag acg tcg 5952Pro Thr Pro Pro Ala Glu Leu His Lys Thr Leu Ala His Gln Thr Ser197019751980gcc gac caa cgg gcc gca ttg ctc gag ctc gta cga gac cat gtg gcg 6000Ala Asp Gln Arg Ala Ala Leu Leu Glu Leu Val Arg Asp His Val Ala1985 199019952000gca gtg ctc cgg cac gcg gac ccg aaa gcc atc gcg ccc gac cag tcg 6048Ala Val Leu Arg His Ala Asp Pro Lys Ala Ile Ala Pro Asp Gln Ser200520102015ttc cgt gca ctc ggc ttc gat tca ctc acg gcc gtc gag ttc cga aac 6096Phe Arg Ala Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Phe Arg Asn202020252030ctg ctg atc aag gca aca gga ctc cgc ctt cct gtc tcg ctg gtc ttc 6144Leu Leu Ile Lys Ala Thr Gly Leu Arg Leu Pro Val Ser Leu Val Phe203520402045gac cac ccg acc cct gcc aaa ctc gcc gta cac ctg cag aac caa ctg 6192Asp His Pro Thr Pro Ala Lys Leu Ala Val His Leu Gln Asn Gln Leu205020552060cgg ggc aca gca gcg gag tcg gct cct tca gcg gca gcc gtt acc gcc 6240Arg Gly Thr Ala Ala Glu Ser Ala Pro Ser Ala Ala Ala Val Thr Ala2065 207020752080gag gct tct gtc acc gag ccg atc gcc atc gtt ggc atg gcc tgt cgt 6288Glu Ala Ser Val Thr Glu Pro Ile Ala Ile Val Gly Met Ala Cys Arg208520902095ttc ccc ggc gga gtg acc tcg gcg gac gac ttc tgg gat ctg atc tcc 6336Phe Pro Gly Gly Val Thr Ser Ala Asp Asp Phe Trp Asp Leu Ile Ser210021052110tcc gag cag gac gcg atc ggc gga ttc ccc acc gac cgc ggc tgg gac 6384Ser Glu Gln Asp Ala Ile Gly Gly Phe Pro Thr Asp Arg Gly Trp Asp211521202125ctg gac acg ctc tac gac ccc gac ccc gac cac ccc ggc acc tgc tac 6432Leu Asp Thr Leu Tyr Asp Pro Asp Pro Asp His Pro Gly Thr Cys Tyr213021352140acc cga aac ggc gga ttc ctc tac gac gca ggc cac ttc gac gcc gaa 6480Thr Arg Asn Gly Gly Phe Leu Tyr Asp Ala Gly His Phe Asp Ala Glu2145 215021552160ttc ttc ggc atc agc ccc cgc gaa gcc ctc gcc atg gac ccc cag caa 6528Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln216521702175cga ctc ctc ctc gaa acc gcc tgg gaa acc atc gaa cac gcc ggc atc 6576Arg Leu Leu Leu Glu Thr Ala Trp Glu Thr Ile Glu His Ala Gly Ile218021852190aac ccc cac acc ctc cac ggc acc ccc acc gga gtc ttc acc ggc acc 6624Asn Pro His Thr Leu His Gly Thr Pro Thr Gly Val Phe Thr Gly Thr219522002205aac gga cag gac tac gca ctt cgc gtg cac aac gcg ggc cag tca acc 6672Asn Gly Gln Asp Tyr Ala Leu Arg Val His Asn Ala Gly Gln Ser Thr221022152220gat ggt ttc gca ctg acc gga acc gcc ggc agc gtc atc tcc ggt cgt 6720Asp Gly Phe Ala Leu Thr Gly Thr Ala Gly Ser Val Ile Ser Gly Arg2225 223022352240atc tcg tac acg ttt ggt ttt gag ggt cct gcg gtg tcg gtg gac acg 6768Ile Ser Tyr Thr Phe Gly Phe Glu Gly Pro Ala Val Ser Val Asp Thr224522502255gct tgt tcc tcg tcg ttg gtg gct ttg cat ctg gcc tgt cag gcg ttg 6816Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys Gln Ala Leu226022652270cgt gcg ggt gag tgc tcg atg gcg ctt gcc ggg ggt gtg acg gtg atg 6864Arg Ala Gly Glu Cys Ser Met Ala Leu Ala Gly Gly Val Thr Val Met227522802285tcg tct ccg ggt gcc ttc gtg gag ttt tcg cgg cag cgg ggt ctg gcc 6912Ser Ser Pro Gly Ala Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala229022952300gcg gac ggg cat tgc aag gcg ttc tcg gcg gcg gcg gac ggg acc ggc 6960Ala Asp Gly His Cys Lys Ala Phe Ser Ala Ala Ala Asp Gly Thr Gly2305 231023152320tgg ggt gag ggt gtg ggg atg ctg ctg gtg gag cgg ctc tcc gac gcc 7008Trp Gly Glu Gly Val Gly Met Leu Leu Val Glu Arg Leu Ser Asp Ala232523302335cat cgc aac ggt cac cgt gtc ctg gcc gtg gtg cgt ggc agt gcg gtc 7056His Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val234023452350aac cag gac ggt gcg agc aac ggt ctg acc gcg ccc aac ggg ccg tcc 7104Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser235523602365cag cag cgt gtc atc cgc cag gcc ctc gcc aac gcc ggc ttg tcg gcc 7152Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Ser Ala237023752380ggt gat gtc gac gcg gtg gag gcc cac ggc acc ggc acc act ttg ggc 7200Gly Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Thr Leu Gly2385 239023952400gac ccg atc gag gcc cag gcc ctc ctc gcg acc tac gga cag gac cgt 7248Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Asp Arg240524102415gcc ggc gag ggg ccg ctg tgg ctg ggc tcg gtc aag tcc aat gtc ggt 7296Ala Gly Glu Gly Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Val Gly242024252430cac aca cag gct gcc gcg ggc gtc gcc ggg gtg atc aag atg gtg atg 7344His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met243524402445gcg ctg cgg cat ggt ctg ctg ccg cgg acg ttg cat gtg gat gag ccg 7392Ala Leu Arg His Gly Leu Leu Pro Arg Thr Leu His Val Asp Glu Pro245024552460tcg ccg cat gtg gac tgg tcc gcg ggt gcg gtg cag ctg ctg acg gag 7440Ser Pro His Val Asp Trp Ser Ala Gly Ala Val Gln Leu Leu Thr Glu2465 247024752480acg gtg ccc tgg ccc ggc ggg gag ggg cgg cta cgg cgg gca gga gtg 7488Thr Val Pro Trp Pro Gly Gly Glu Gly Arg Leu Arg Arg Ala Gly Val248524902495tca tca ttc ggc gtc agc ggc acc aac gcc cac gtc atc ctc gaa gaa 7536Ser Ser Phe Gly Val Ser Gly Thr Asn Ala His Val Ile Leu Glu Glu250025052510gca ccc gcc gac gac gtt ccg ggg gga cca ccc gcc ggc gag ggt gac 7584Ala Pro Ala Asp Asp Val Pro Gly Gly Pro Pro Ala Gly Glu Gly Asp251525202525gcg ggc agc gac gat gag gct gct gcc ggc agt cct ggg gtg tgg ccg 7632Ala Gly Ser Asp Asp Glu Ala Ala Ala Gly Ser Pro Gly Val Trp Pro253025352540tgg ctg gtg tcg gcc aag tcg cag ccg gcc ctg cgc gcc cag gcc cag 7680Trp Leu Val Ser Ala Lys Ser Gln Pro Ala Leu Arg Ala Gln Ala Gln2545 255025552560gcc ctg cac gcc cac ctc acc gac cac ccc ggc ctc gac ctc gcg gat 7728Ala Leu His Ala His Leu Thr Asp His Pro Gly Leu Asp Leu Ala Asp256525702575gtc gga tac acc ctc gcc cac gcc cgc gcc gtg ttc gac cac cgc gcc 7776Val Gly Tyr Thr Leu Ala His Ala Arg Ala Val Phe Asp His Arg Ala258025852590acc ctc atc gcc gcg gac cgc gac acg ttc ctg caa gca ctc cag gca 7824Thr Leu Ile Ala Ala Asp Arg Asp Thr Phe Leu Gln Ala Leu Gln Ala259526002605ctc gcc gca ggc gag ccc cac ccc gcc gtc atc cac agc agc gcc ccg 7872Leu Ala Ala Gly Glu Pro His Pro Ala Val Ile His Ser Ser Ala Pro261026152620ggc ggg acc ggg acc ggg gag gcc gca gga aag acc gca ttc atc tgc 7920Gly Gly Thr Gly Thr Gly Glu Ala Ala Gly Lys Thr Ala Phe Ile Cys2625 263026352640tcc gga cag ggc acc caa cgc ccc ggc atg gcc cac ggc ctc tac cac 7968Ser Gly Gln Gly Thr Gln Arg Pro Gly Met Ala His Gly Leu Tyr His264526502655acc cac ccc gtc ttc gcc gcc gca ctc aac gac atc tgc acc cac ctc 8016Thr His Pro Val Phe Ala Ala Ala Leu Asn Asp Ile Cys Thr His Leu266026652670gac ccc cac ctc gac cac ccc ctc ctc ccc ctc ctc acc caa aac gac 8064Asp Pro His Leu Asp His Pro Leu Leu Pro Leu Leu Thr Gln Asn Asp267526802685aac gac aac gag gac gcg gcc gca ctg ctc cag cag acc cgc tac gcc 8112Asn Asp Asn Glu Asp Ala Ala Ala Leu Leu Gln Gln Thr Arg Tyr Ala269026952700cag ccc gcc ctc ttc gcc ttc cag gtc gcc ctc cac cgc ctc ctc acc 8160Gln Pro Ala Leu Phe Ala Phe Gln Val Ala Leu His Arg Leu Leu Thr2705 271027152720gac ggc tac cac atc acc ccc cac tac tac gcc gga cac tcc ctc ggc 8208Asp Gly Tyr His Ile Thr Pro His Tyr Tyr Ala Gly His Ser Leu Gly272527302735gaa atc acc gcc gcc cac ctc gcc ggc atc ctc acc ctc acc gac gcc 8256Glu Ile Thr Ala Ala His Leu Ala Gly Ile Leu Thr Leu Thr Asp Ala274027452750acc acc ctc atc acc caa cgc gcc acc ctc atg caa acc atg ccc ccc 8304Thr Thr Leu Ile Thr Gln Arg Ala Thr Leu Met Gln Thr Met Pro Pro275527602765ggc acc atg acc acc ctc cac acc acc ccc cac cac atc acc cac cac 8352Gly Thr Met Thr Thr Leu His Thr Thr Pro His His Ile Thr His His277027752780ctc acc gcc cac gaa aac gac ctc gcc atc gcc gcc atc aac acc ccc 8400Leu Thr Ala His Glu Asn Asp Leu Ala Ile Ala Ala Ile Asn Thr Pro2785 279027952800acc tcc ctc gtc atc agc ggc acc ccc cac acc gtc caa cac atc acc 8448Thr Ser Leu Val Ile Ser Gly Thr Pro His Thr Val Gln His Ile Thr280528102815acc ctc tgc caa caa caa ggc atc aaa acc aaa acc ctc ccc acc aac 8496Thr Leu Cys Gln Gln Gln Gly Ile Lys Thr Lys Thr Leu Pro Thr Asn282028252830cac gcc ttc cac tcc ccc cac acc aac ccc atc ctc aac caa ctc cac 8544His Ala Phe His Ser Pro His Thr Asn Pro Ile Leu Asn Gln Leu His283528402845cag cac acc caa acc ctc acc tac cac cca ccc cac acc ccc ctc atc 8592Gln His Thr Gln Thr Leu Thr Tyr His Pro Pro His Thr Pro Leu Ile285028552860acc gcc aac acc cca ccc gac caa ctc ctc acc ccc cac tac tgg acc 8640Thr Ala Asn Thr Pro Pro Asp Gln Leu Leu Thr Pro His Tyr Trp Thr2865 287028752880caa caa gcc cgc aac acc gtc gac tac gcc acc acc acc caa acc ctc 8688Gln Gln Ala Arg Asn Thr Val Asp Tyr Ala Thr Thr Thr Gln Thr Leu288528902895cac caa cac ggc gtc acc acc tac atc gaa ctc gga ccc gac aac acc 8736His Gln His Gly Val Thr Thr Tyr Ile Glu Leu Gly Pro Asp Asn Thr290029052910ctc acc acc ctc acc cac cac aac ctc ccc aac ccc ccc acc acc acc 8784Leu Thr Thr Leu Thr His His Asn Leu Pro Asn Pro Pro Thr Thr Thr291529202925ctc acc ctc acc cac ccc cac cac cac ccc caa acc cac ctc ctc acc 8832Leu Thr Leu Thr His Pro His His His Pro Gln Thr His Leu Leu Thr293029352940aac ctc gcc aaa acc acc acc acc tgg cac ccc cac cac tac acc cac 8880Asn Leu Ala Lys Thr Thr Thr Thr Trp His Pro His His Tyr Thr His2945 295029552960cac gac aac caa ccc cac acc cac acc cac ctc gac ctc ccc acc tac 8928His Asp Asn Gln Pro His Thr His Thr His Leu Asp Leu Pro Thr Tyr296529702975ccc ttc caa cac cac cac tac tgg ctc gaa agc aca cag ccc ggt gcc 8976Pro Phe Gln His His His Tyr Trp Leu Glu Ser Thr Gln Pro Gly Ala298029852990ggc aac gtg tca gca gcc gga ctc gac ccc acc gaa cac ccc cta ctc 9024Gly Asn Val Ser Ala Ala Gly Leu Asp Pro Thr Glu His Pro Leu Leu299530003005ggc gcc aca ttg gaa ctg gcg act gac ggt gga gcg ctt ctt gca ggg 9072Gly Ala Thr Leu Glu Leu Ala Thr Asp Gly Gly Ala Leu Leu Ala Gly301030153020cgc ttg tct ttg agg tcg cat ccg tgg ctg gct gac cat gcc gtc ggc 9120Arg Leu Ser Leu Arg Ser His Pro Trp Leu Ala Asp His Ala Val Gly3025 303030353040ggc acg gtg ctg ctg tcg ggc gcc acc ttc ctc gaa ctc gcc ctt cat 9168Gly Thr Val Leu Leu Ser Gly Ala Thr Phe Leu Glu Leu Ala Leu His304530503055gcg ggc aca tac gtg ggc tgc gac cga gtg gat gag ctg acg ctg cat 9216Ala Gly Thr Tyr Val Gly Cys Asp Arg Val Asp Glu Leu Thr Leu His306030653070gcg ccg ctg gtg gtt cct gtg gat ggg ggt gtg agt gtg cag gtt ggg 9264Ala Pro Leu Val Val Pro Val Asp Gly Gly Val Ser Val Gln Val Gly307530803085gtt gcg gct gcg gat ggg gag ggg cgg cgt ttg gtg agt gtg tat gcg 9312Val Ala Ala Ala Asp Gly Glu Gly Arg Arg Leu Vat Ser Val Tyr Ala309030953100cgg ggt ggg agt gct tgt ggt ggg ggt ggt gcg tcg ggt ggg gtg tgg 9360Arg Gly Gly Ser Ala Cys Gly Gly Gly Gly Ala Ser Gly Gly Val Trp3105 311031153120acg tgt cat gcc tcg ggg gtg ctg gtt gag gct gct gct ggt ggt gtg 9408Thr Cys His Ala Ser Gly Val Leu Val Glu Ala Ala Ala Gly Gly Val312531303135gtg gtg gat ggt ctg gcg ggg gtg tgg ccg ccg cgg ggt gcg gtg gcg 9456Val Val Asp Gly Leu Ala Gly Val Trp Pro Pro Arg Gly Ala Val Ala314031453150gtg gat gtc gat ggt gtc cgt gac cgt ttg gct ggg gct ggt tgt gtt 9504Val Asp Val Asp Gly Val Arg Asp Arg Leu Ala Gly Ala Gly Cys Val315531603165ttg ggg ccg gtg ttt tcg ggg ctg cgt gcg gtg tgg cgt gat ggg ggg 9552Leu Gly Pro Val Phe Ser Gly Leu Arg Ala Val Trp Arg Asp Gly Gly317031753180gat ttg ctg gct gag gtg tgt ctg ccg gag gag gcg tgg ggt gat gcg 9600Asp Leu Leu Ala Glu Val Cys Leu Pro Glu Glu Ala Trp Gly Asp Ala3185 319031953200gct ggt ttt ggg ctg cat ccg gcg ttg ctg gat ggt gtg gtc cag ccg 9648Ala Gly Phe Gly Leu His Pro Ala Leu Leu Asp Gly Val Val Gln Pro320532103215ttg tcg gtg ttg ctt ccg ggt ggg acg ggg ttt ggg gag ggg gcg ggg 9696Leu Ser Val Leu Leu Pro Gly Gly Thr Gly Phe Gly Glu Gly Ala Gly322032253230ttc ggg gag ggt gtt cgg gtg ccg gct gtg tgg ggt ggt gtg tcg ctt 9744Phe Gly Glu Gly Val Arg Val Pro Ala Val Trp Gly Gly Val Ser Leu323532403245cac cgg gcg ggt gtg acc ggt gtg cgg gtg cgt gtg tcg gct gtc ggg 9792His Arg Ala Gly Val Thr Gly Val Arg Val Arg Val Ser Ala Val Gly325032553260cgg ggc ggc ggg cgt gag gcg gtg tcg gtc gtg gtc ggg gat gag gcg 9840Arg Gly Gly Gly Arg Glu Ala Val Ser Val Val Val Gly Asp Glu Ala3265 327032753280ggt gtg ccg gtg gcg tcg gtc gat cgt ctt gag ttg cgg cct gtg gat 9888Gly Val Pro Val Ala Ser Val Asp Arg Leu Glu Leu Arg Pro Val Asp328532903295atg ggt cag ttg cgt gct gtc tcg gtt tcg gcg ggg cgg cgg ggt tcg 9936Met Gly Gln Leu Arg Ala Val Ser Val Ser Ala Gly Arg Arg Gly Ser330033053310ctg tat gcg gtg cag tgg gct gag gtg ggt cct gtg ccg gtg tgt ggg 9984Leu Tyr Ala Val Gln Trp Ala Glu Val Gly Pro Val Pro Val Cys Gly331533203325cag gcg tgg gcg tgg cac gag gac gtg ggt gag agc ggt ggt ggg cct 10032Gln Ala Trp Ala Trp His Glu Asp Val Gly Glu Ser Gly Gly Gly Pro333033353340gtg ccg ggg gtg gtg gtg ttg cgg tgc ccg gat gcc ggt gcc ggt ggc 10080Val Pro Gly Val Val Val Leu Arg Cys Pro Asp Ala Gly Ala Gly Gly3345 335033553360ggt ggc ggt ggc ggt ggt ggc ggt ggt gtg ggt gag gtt gtt ggt ggg 10128Gly Gly Gly Gly Gly Gly Gly Gly Gly Val Gly Glu Val Val Gly Gly336533703375gtg ttg ggt gtg gtg cag ggg tgg ctg ggg ctg gag cgg ttt gcg ggt 10176Val Leu Gly Val Val Gln Gly Trp Leu Gly Leu Glu Arg Phe Ala Gly338033853390tcg cgg ctg gtg gtg gtg acc cgg ggt gcg gtg gtg gcc ggc ccg gag 10224Ser Arg Leu Val Val Val Thr Arg Gly Ala Val Val Ala Gly Pro Glu339534003405gac ggc ccg gtg gat gtg gtg ggt gcg tcg gtg tgg ggg ctg gtg cgt 10272Asp Gly Pro Val Asp Val Val Gly Ala Ser Val Trp Gly Leu Val Arg341034153420tcg gcg cag gct gag cat ccg gac cgg ttt gtc ctc ctc gac ctc gac 10320Ser Ala Gln Ala Glu His Pro Asp Arg Phe Val Leu Leu Asp Leu Asp3425 343034353440acc gac acc ggc acc gac ctc gac acc ggt gct ggt gct ggt tgg ggc 10368Thr Asp Thr Gly Thr Asp Leu Asp Thr Gly Ala Gly Ala Gly Trp Gly344534503455gtg gat ggt ggg cgt gtg gcg gcg gtg gtg gcg tgt ggt gag ccg cag 10416Val Asp Gly Gly Arg Val Ala Ala Val Val Ala Cys Gly Glu Pro Gln346034653470ttg gcg gtg cgt ggg gag cgg ttg ctg gcc gca cgc ctg aaa cga ctt 10464Leu Ala Val Arg Gly Glu Arg Leu Leu Ala Ala Arg Leu Lys Arg Leu347534803485gag tca tcc ggt gat gtt cca gcc cag cgg tcc ggt gac aca cga gcc 10512Glu Ser Ser Gly Asp Val Pro Ala Gln Arg Ser Gly Asp Thr Arg Ala349034953500cgg cgg tcc gac gtg cct gcc cag cgc tcc ggt ggc gtg cct gct cgg 10560Arg Arg Ser Asp Val Pro Ala Gln Arg Ser Gly Gly Val Pro Ala Arg3505 351035153520cgg tcg gtt gat gta tcg ggt cgg gag gtg ttg ccg tgg ttg tcg ggt 10608Arg Ser Val Asp Val Ser Gly Arg Glu Val Leu Pro Trp Leu Ser Gly352535303535ggg tcg gtg ttg gtg acg ggt ggg acg ggt gtg ctg ggt gcg gcg gtg 10656Gly Ser Val Leu Val Thr Gly Gly Thr Gly Val Leu Gly Ala Ala Val354035453550gcg cgg cat ctg gct ggt gtg tgt ggg gtg cgg gat ctg ctg ttg gtg 10704Ala Arg His Leu Ala Gly Val Cys Gly Val Arg Asp Leu Leu Leu Val355535603565agc cgg cgt ggt ccg gat gct ccg ggt gcg gag ggt ctg cgg gcg gag 10752Ser Arg Arg Gly Pro Asp Ala Pro Gly Ala Glu Gly Leu Arg Ala Glu357035753580ctg gcc gcg ttg ggg gcg gag gtg cgg att gtt gcg tgt gat gtg ggg 10800Leu Ala Ala Leu Gly Ala Glu Val Arg Ile Val Ala Cys Asp Val Gly3585 359035953600gag cgg cgg gag gtg gtc cgg ctg ctg gag ggt gtt cct gcc ggg tgt 10848Glu Arg Arg Glu Val Val Arg Leu Leu Glu Gly Val Pro Ala Gly Cys360536103615ccg ctg acg ggt gtc gtg cat gcg gct ggt gtg ctg gac gat gcg acg 10896Pro Leu Thr Gly Val Val His Ala Ala Gly Val Leu Asp Asp Ala Thr362036253630atc gcc tct ctc acg ccc gag cgg ctg ggc acg gtg ttc gcg gcc aag 10944Ile Ala Ser Leu Thr Pro Glu Arg Leu Gly Thr Val Phe Ala Ala Lys363536403645gtg gat gcc gct ctt ttg ctg gat gag ctg acg cgg ggt atg gag ctg 10992Val Asp Ala Ala Leu Leu Leu Asp Glu Leu Thr Arg Gly Met Glu Leu365036553660tcg gcg ttc gtg ctg ttc tcc tcg gcc gcg ggg atc ctg ggg tcg gcc 11040Ser Ala Phe Val Leu Phe Ser Ser Ala Ala Gly Ile Leu Gly Ser Ala3665 367036753680ggg cag ggc aac tac gcc gcg gcc aat gcc gct ctg gac gcg ctg gcg 11088Gly Gln Gly Asn Tyr Ala Ala Ala Asn Ala Ala Leu Asp Ala Leu Ala368536903695tac cgg cgg cgg gcg gcg ggt ctg ccg ggg gtg tcg ctg gcg tgg ggg 11136Tyr Arg Arg Arg Ala Ala Gly Leu Pro Gly Val Ser Leu Ala Trp Gly370037053710ctg tgg gaa gag gcc agc ggg atg acc ggg cac ctg gcc ggc acc gac 11184Leu Trp Glu Glu Ala Ser Gly Met Thr Gly His Leu Ala Gly Thr Asp371537203725cac cgg cgc atc atc cgt tcc ggt ctg cat ccc atg tcg acc ccg gac 11232His Arg Arg Ile Ile Arg Ser Gly Leu His Pro Met Ser Thr Pro Asp373037353740gca ctg gcc ctc ttc gat gcg gcc ctg gct ctg gac cgg ccg gtc ctg 11280Ala Leu Ala Leu Phe Asp Ala Ala Leu Ala Leu Asp Arg Pro Val Leu3745 375037553760ctg ccc gcc gac ctg cgt ccc gcc ccg ccc ctg ccg ccc ctg ctg cag 11328Leu Pro Ala Asp Leu Arg Pro Ala Pro Pro Leu Pro Pro Leu Leu Gln376537703775gac ctc ctg ccc gcc acc cgc cgc cgc acc acc cgc acc acc act acc 11376Asp Leu Leu Pro Ala Thr Arg Arg Arg Thr Thr Arg Thr Thr Thr Thr378037853790ggt ggt gcg gac aac ggc gcc cag ctg cac gcc cgg ctg gcc ggc cag 11424Gly Gly Ala Asp Asn Gly Ala Gln Leu His Ala Arg Leu Ala Gly Gln379538003805aca cac gaa caa cag cac acc acc ctc ctc gcc ctg gtc cgc tcc cac 11472Thr His Glu Gln Gln His Thr Thr Leu Leu Ala Leu Val Arg Ser His381038153820atc gcc acc gtc ctg ggc cac acc acc ccc gac acc atc ccc ccc gac 11520Ile Ala Thr Val Leu Gly His Thr Thr Pro Asp Thr Ile Pro Pro Asp3825 383038353840cgc gcg ttc cgc gac ctc ggc ttc gac tcc ctc acc gcc gtc gaa cta 11568Arg Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu384538503855cgc aac cgg ctc tcc cgc acc acc gga ctc cgc ctc ccc acc acc ctc 11616Arg Asn Arg Leu Ser Arg Thr Thr Gly Leu Arg Leu Pro Thr Thr Leu386038653870gcc ttc gac cac ccc aac ccc acc acc ctc acc cac cac ctc cac aca 11664Ala Phe Asp His Pro Asn Pro Thr Thr Leu Thr His His Leu His Thr387538803885caa ctc cag cca caa ccg gac aac gct gtc gcc ccc gtg ttg gcg gag 11712Gln Leu Gln Pro Gln Pro Asp Asn Ala Val Ala Pro Val Leu Ala Glu389038953900ctc gac aaa ctc gaa tcc gcc ctc tcc gcc ctc gac aaa acc gac agc 11760Leu Asp Lys Leu Glu Ser Ala Leu Ser Ala Leu Asp Lys Thr Asp Ser3905 391039153920gcc agc gaa aga gtc acc ctg cgg ctg aag tca ctc atg ttg agg tgg 11808Ala Ser Glu Arg Val Thr Leu Arg Leu Lys Ser Leu Met Leu Arg Trp392539303935aac gca ccc cag cat ccg aca gcc gaa agc gct gat gac gac gag aag 11856Asn Ala Pro Gln His Pro Thr Ala Glu Ser Ala Asp Asp Asp Glu Lys394039453950ttc aca tcg gca aca gag gct gag att ttc aaa ttc att gac aac gac 11904Phe Thr Ser Ala Thr Glu Ala Glu Ile Phe Lys Phe Ile Asp Asn Asp395539603965ctc ggc ctg tcc tgaaccggac gcctgccact ccgcccgtat ccgctgggcc 11956Leu Gly Leu Ser3970ctgctaggac gtga atg caa ttg gcg aat gaa gcg aag ctc ctg gaa tac 12006Met Gln Leu Ala Asn Glu Ala Lys Leu Leu Glu Tyr39753980ctc aag cgc gtc act gcg gac ctg gac cgc act cgc cgt cgc ctg tac 12054Leu Lys Arg Val Thr Ala Asp Leu Asp Arg Thr Arg Arg Arg Leu Tyr3985 399039954000gag gtg gtc gag cgt gag cag gag ccg atc gcg att gtg ggg atg gcg 12102Glu Val Val Glu Arg Glu Gln Glu Pro Ile Ala Ile Val Gly Met Ala400540104015tgt cgt tac cca ggc ggg gcg acg tca ccc acg cga ctg tgg cat ctc 12150Cys Arg Tyr Pro Gly Gly Ala Thr Ser Pro Thr Arg Leu Trp His Leu402040254030gtc aag tcc cag acg gac gct atc ggg gag ttc ccg acc gac cgt gga 12198Val Lys Ser Gln Thr Asp Ala Ile Gly Glu Phe Pro Thr Asp Arg Gly403540404045tgg aac ctg gag cag ctc tac gac ccg gac ccc gac cgc tca gga acc 12246Trp Asn Leu Glu Gln Leu Tyr Asp Pro Asp Pro Asp Arg Ser Gly Thr405040554060agt tac acg cgc agc gga ggg ttt ctc tat gac gcg ggc gac ttc gac 12294Ser Tyr Thr Arg Ser Gly Gly Phe Leu Tyr Asp Ala Gly Asp Phe Asp4065 407040754080gcc gcg ttc ttc gag ttg tca ccg cgt gag gcg ctg gca atg gac ccg 12342Ala Ala Phe Phe Glu Leu Ser Pro Arg Glu Ala Leu Ala Met Asp Pro408540904095cag cag cgc ctg ctg ctc gaa acc act tgg gaa acg ttc gaa cag ggc 12390Gln Gln Arg Leu Leu Leu Glu Thr Thr Trp Glu Thr Phe Glu Gln Gly410041054110gga atc gac ccg agg tcc atg cgc gga agc cgg acc ggg gtt ttc gtg 12438Gly Ile Asp Pro Arg Ser Met Arg Gly Ser Arg Thr Gly Val Phe Val411541204125ggg atc aat ccg gag gac tac acc acc gga tac aca cat cag ccc tca 12486Gly Ile Asn Pro Glu Asp Tyr Thr Thr Gly Tyr Thr His Gln Pro Ser413041354140aac gca gtc gag ggc tac ctg ctc act ggc agc gcg gca agc att gcg 12534Asn Ala Val Glu Gly Tyr Leu Leu Thr Gly Ser Ala Ala Ser Ile Ala4145 415041554160tca ggc cgt atc tcc tac aac ttc ggg ctc gaa ggc cct gcg atc act 12582Ser Gly Arg Ile Ser Tyr Asn Phe Gly Leu Glu Gly Pro Ala Ile Thr416541704175atc gac acc gcg tgt tcc tcc tcg ctc gtc gcc ctg cat ctg gcc tgc 12630Ile Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys418041854190caa gcg ctc cgg tcc ggt gaa tgc acc atg gcg ctc gca ggc ggc gcc 12678Gln Ala Leu Arg Ser Gly Glu Cys Thr Met Ala Leu Ala Gly Gly Ala419542004205tcc gtc atg gcc act ccc ttc gtc ttc acc gag ttc tct cgc cag cgg 12726Ser Val Met Ala Thr Pro Phe Val Phe Thr Glu Phe Ser Arg Gln Arg421042154220ggc ctg gcc gca gac ggc cgg tgc aag gcg ttt tcg gcg gcg gcg gac 12774Gly Leu Ala Ala Asp Gly Arg Cys Lys Ala Phe Ser Ala Ala Ala Asp4225 423042354240ggg acc ggc tgg tcc gag ggt gtg ggg atg ctg ctg gtg gag cgg ctc 12822Gly Thr Gly Trp Ser Glu Gly Val Gly Met Leu Leu Val Glu Arg Leu424542504255tcc gac gcc cgc cgc aac ggt cac cgt gtc ctg gcc gtc gtc cgc ggc 12870Ser Asp Ala Arg Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly426042654270agc gcc gtc aac cag gac ggc gca agc aac ggc ctg acc gca ccc aac 12918Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn427542804285ggt cgt tca caa gtc aag gtc atc cgc cag gct ttg gcc aac gca cac 12966Gly Arg Ser Gln Val Lys Val Ile Arg Gln Ala Leu Ala Asn Ala His429042954300ctc tcc cct gcc gat gtc gat gcg gtg gag gcc cac ggc acg ggg acc 13014Leu Ser Pro Ala Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr4305 431043154320acc ctg ggc gac ccg atc gag gct caa gcc ctc gtc gaa gcc tac ggt 13062Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Val Glu Ala Tyr Gly432543304335cag gac cgc ccc aac ggc cgc ccc ctc tgg ctc gga acc ctc aag tcc 13110Gln Asp Arg Pro Asn Gly Arg Pro Leu Trp Leu Gly Thr Leu Lys Ser434043454350aac atc ggg cac tcc atg gcc gct gcg ggt gtg ggc ggg gtc atc aag 13158Asn Ile Gly His Ser Met Ala Ala Ala Gly Val Gly Gly Val Ile Lys435543604365atg gtg atg gcg ctg cgg aat ggt ctg ctg ccg cgg acg ttg cat gtg 13206Met Val Met Ala Leu Arg Asn Gly Leu Leu Pro Arg Thr Leu His Val437043754380gat gag ccg tcg ccg cat gtg gac tgg tcc gcg ggt gcg gtg cag ctg 13254Asp Glu Pro Ser Pro His Val Asp Trp Ser Ala Gly Ala Val Gln Leu4385 439043954400ctg acg gag acg gtg ccc tgg ccc ggc ggg gag ggg cgg cta cgg cgg 13302Leu Thr Glu Thr Val Pro Trp Pro Gly Gly Glu Gly Arg Leu Arg Arg440544104415gca gga gtg tca tca ttc ggc gtc agc ggc acc aac gcc cac gtc atc 13350Ala Gly Val Ser Ser Phe Gly Val Ser Gly Thr Asn Ala His Val Ile442044254430ctc gag gaa gca ccc gcc cac aac atc ccg tca gac aca ccc gcc gac 13398Leu Glu Glu Ala Pro Ala His Asn Ile Pro Ser Asp Thr Pro Ala Asp443544404445gac gtc ccg gga gaa tca gcc gcc gac gag gat gcc ggt agt ggc gat 13446Asp Val Pro Gly Glu Ser Ala Ala Asp Glu Asp Ala Gly Ser Gly Asp445044554460gag gct gct gcc ggc agt cca ggg gtg tgg ccg tgg ctg gtg tcg gcc 13494Glu Ala Ala Ala Gly Ser Pro Gly Val Trp Pro Trp Leu Val Ser Ala4465 447044754480aag tcg cag ccg gcc ctg cgc gcc cag gcc cag gcc ctg cac gcc cac 13542Lys Ser Gln Pro Ala Leu Arg Ala Gln Ala Gln Ala Leu His Ala His448544904495ctc acc gac cac ccc ggc ctc gac ctc gcc gac gtc ggg tac acc ctc 13590Leu Thr Asp His Pro Gly Leu Asp Leu Ala Asp Val Gly Tyr Thr Leu450045054510gcc cac gcc cgc gcc gtg ttc gac cac cgc gcc acc ctc atc gcc gcc 13638Ala His Ala Arg Ala Val Phe Asp His Arg Ala Thr Leu Ile Ala Ala451545204525gac cgc gac acc ttc ctg caa gca ctc cag gca ctc gcc gca ggc gaa 13686Asp Arg Asp Thr Phe Leu Gln Ala Leu Gln Ala Leu Ala Ala Gly Glu453045354540ccc cac ccc gcc gtc atc cac agc agc gcc cca ggc ggg acc ggg acc 13734Pro His Pro Ala Val Ile His Ser Ser Ala Pro Gly Gly Thr Gly Thr4545 455045554560ggg gag gcc gca gga aag acc gca ttc atc tgc tcc gga cag ggc acc 13782Gly Glu Ala Ala Gly Lys Thr Ala Phe Ile Cys Ser Gly Gln Gly Thr456545704575caa cgc ccc ggc atg gcc cac ggc ctc tac cac acc cac ccc gtc ttc 13830Gln Arg Pro Gly Met Ala His Gly Leu Tyr His Thr His Pro Val Phe458045854590gcc gcc gca ctc aac gac atc tgc acc cac ctc gac ccc cac ctc gac 13878Ala Ala Ala Leu Asn Asp Ile Cys Thr His Leu Asp Pro His Leu Asp459546004605cac ccc ctc ctc ccc ctc ctc acc cag gac ccc aac acc cag gac acc 13926His Pro Leu Leu Pro Leu Leu Thr Gln Asp Pro Asn Thr Gln Asp Thr461046154620acc acc ctc gaa gaa gcg gcc gca ctg ctc cag cag acc cgc tac gcc 13974Thr Thr Leu Glu Glu Ala Ala Ala Leu Leu Gln Gln Thr Arg Tyr Ala4625 463046354640cag ccc gcc ctc ttc gcc ttc cag gtc gcc ctc cac cgc ctc ctc acc 14022Gln Pro Ala Leu Phe Ala Phe Gln Val Ala Leu His Arg Leu Leu Thr464546504655gac ggc tac cac atc acc ccc cac tac tac gcc gga cac tcc ctc ggc 14070Asp Gly Tyr His Ile Thr Pro His Tyr Tyr Ala Gly His Ser Leu Gly466046654670gaa atc acc gcc gcc cac ctc gcc ggc atc ctc acc ctc acc gac gcc 14118Glu Ile Thr Ala Ala His Leu Ala Gly Ile Leu Thr Leu Thr Asp Ala467546804685acc acc ctc atc acc caa cgc gcc acc ctc atg caa acc atg ccc ccc 14166Thr Thr Leu Ile Thr Gln Arg Ala Thr Leu Met Gln Thr Met Pro Pro469046954700ggc acc atg acc acc ctc cac acc acc ccc cac cac atc acc cac cac 14214Gly Thr Met Thr Thr Leu His Thr Thr Pro His His Ile Thr His His4705 471047154720ctc acc gcc cac gaa aac gac ctc gcc atc gcc gcc atc aac acc ccc 14262Leu Thr Ala His Glu Asn Asp Leu Ala Ile Ala Ala Ile Asn Thr Pro@ @ @ @ @ @ @472547304735acc tcc ctc gtc atc agc ggc acc ccc cac acc gtc caa cac atc acc 14310Thr Ser Leu Val Ile Ser Gly Thr Pro His Thr Val Gln His Ile Thr474047454750acc ctc tgc caa caa caa ggc atc aaa acc aaa acc ctc ccc acc aac 14358Thr Leu Cys Gln Gln Gln Gly Ile Lys Thr Lys Thr Leu Pro Thr Asn475547604765cac gcc ttc cac tcc ccc cac acc aac ccc atc ctc aac caa ctc cac 14406His Ala Phe His Ser Pro His Thr Asn Pro Ile Leu Asn Gln Leu His477047754780cag cac acc caa acc ctc acc tac cac cca ccc cac acc ccc ctc atc 14454Gln His Thr Gln Thr Leu Thr Tyr His Pro Pro His Thr Pro Leu Ile4785 479047954800acc gcc aac acc cca ccc gac caa ctc ctc acc ccc cac tac tgg acc 14502Thr Ala Asn Thr Pro Pro Asp Gln Leu Leu Thr Pro His Tyr Trp Thr480548104815caa caa gcc cgc aac acc gtc gac tac gcc acc acc acc caa acc ctc 14550Gln Gln Ala Arg Asn Thr Val Asp Tyr Ala Thr Thr Thr Gln Thr Leu482048254830cac caa cac ggc gtc acc acc tac atc gaa ctc gga ccc gac aac acc 14598His Gln His Gly Val Thr Thr Tyr Ile Glu Leu Gly Pro Asp Asn Thr483548404845ctc acc acc ctc acc cac gac aac ctc ccc aac acc ccc acc acc acc 14646Leu Thr Thr Leu Thr His Asp Asn Leu Pro Asn Thr Pro Thr Thr Thr485048554860ctc acc ctc acc cac ccc cac cac cac ccc caa acc cac ctc ctc acc 14694Leu Thr Leu Thr His Pro His His His Pro Gln Thr His Leu Leu Thr4865 487048754880aac ctc gcc aaa acc acc acc acc tgg cac ccc cac cac tac acc cac 14742Asn Leu Ala Lys Thr Thr Thr Thr Trp His Pro His His Tyr Thr His488548904895cac cac aac caa ccc cac acc cac acc cac ctc gac ctc ccc acc tac 14790His His Asn Gln Pro His Thr His Thr His Leu Asp Leu Pro Thr Tyr490049054910ccc ttc caa cac cac cac tac tgg ctc caa cca ccc ggc aag ccg agc 14838Pro Phe Gln His His His Tyr Trp Leu Gln Pro Pro Gly Lys Pro Ser491549204925gac ccg tca ccg agc gaa ggc cgt gag caa gcc acg acc cca tca acc 14886Asp Pro Ser Pro Ser Glu Gly Arg Glu Gln Ala Thr Thr Pro Ser Thr493049354940ccg ctg cgt gat gtc ctc gtg ggc aag tct ccg cag gag cga gac gaa 14934Pro Leu Arg Asp Val Leu Val Gly Lys Ser Pro Gln Glu Arg Asp Glu4945 495049554960gag ctg ttg cgc ctg gtg cgc acc cat gcg gcc gct gtg ctg ggc cat 14982Glu Leu Leu Arg Leu Val Arg Thr His Ala Ala Ala Val Leu Gly His496549704975gcc act ccc gaa gtg atc gtt ccg aac aag gcc ttc aaa gag ctg ggt 15030Ala Thr Pro Glu Val Ile Val Pro Asn Lys Ala Phe Lys Glu Leu Gly4980 4985 4990ttt gat tct ctc gcc gca att cag ctt cgt aat cga ctg ctt gct gac 15078Phe Asp Ser Leu Ala Ala Ile Gln Leu Arg Asn Arg Leu Leu Ala Asp499550005005gtt gac ctg ccg ctt ccg gcc acg ctg atc ttc gat tac ccc act ccg 15126Val Asp Leu Pro Leu Pro Ala Thr Leu Ile Phe Asp Tyr Pro Thr Pro501050155020atg gcg ctt tgc cag ttc ctc cgg gcg gcg atc gtc gga gcg gac aca 15174Met Ala Leu Cys Gln Phe Leu Arg Ala Ala Ile Val Gly Ala Asp Thr5025 503050355040ggc acg acc act cgt ctg ccg cta act gcg gtc ccc gcc gac gag ccg 15222Gly Thr Thr Thr Arg Leu Pro Leu Thr Ala Val Pro Ala Asp Glu Pro504550505055atc gcc atc gtc ggc atg gcc tgt cgg tac ccc ggt gat gta cgg acg 15270Ile Ala Ile Val Gly Met Ala Cys Arg Tyr Pro Gly Asp Val Arg Thr506050655070gtc gat gat ctc tgg cag gtg gtc agt ggt ggc cat gac gcg atc ggc 15318Val Asp Asp Leu Trp Gln Val Val Ser Gly Gly His Asp Ala Ile Gly507550805085gga ttc ccg acg aac cgt ggg tgg gac ctc gac acg ctg tac aac ccg 15366Gly Phe Pro Thr Asn Arg Gly Trp Asp Leu Asp Thr Leu Tyr Asn Pro509050955100gac ccg gac cac cac gga acc agc tac acc cgg agc ggc gga ttc ctt 15414Asp Pro Asp His His Gly Thr Ser Tyr Thr Arg Ser Gly Gly Phe Leu5105 511051155120tac gac gca ggc aat ttc gat ccc gac ttc ttc ggt atc agt ccg cgt 15462Tyr Asp Ala Gly Asn Phe Asp Pro Asp Phe Phe Gly Ile Ser Pro Arg512551305135gag gca ctg gcg atg gac ccg cag cag cgg ctg ctg ctg gaa aca gcg 15510Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Thr Ala514051455150tgg gag agc atc gaa cac gcc tgc atc aac ccc gac agc ctc cgt ggc 15558Trp Glu Ser Ile Glu His Ala Cys Ile Asn Pro Asp Ser Leu Arg Gly515551605165aca cca acc ggc gtc ttc gcc ggg ctg acc tac cac gac tac gcc gcg 15606Thr Pro Thr Gly Val Phe Ala Gly Leu Thr Tyr His Asp Tyr Ala Ala517051755180cgc ttt ccc aca gct ccg gca ggg ttc gag ggg tat ctc ggg cac gga 15654Arg Phe Pro Thr Ala Pro Ala Gly Phe Glu Gly Tyr Leu Gly His Gly5185 519051955200agc gca ggc agt atc gcc tcg ggt cgt gtc gcc tac gct ctc ggc ctg 15702Ser Ala Gly Ser Ile Ala Ser Gly Arg Val Ala Tyr Ala Leu Gly Leu520552105215gaa ggt ccg gcc ctc aca gtc gac act gcc tgc tct tcg tcc ctg gtc 15750Glu Gly Pro Ala Leu Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val522052255230gct ctg cac ctg gcc tgt cag gcg ctg cgg tcc ggc gag tgt tcc atg 15798Ala Leu His Leu Ala Cys Gln Ala Leu Arg Ser Gly Glu Cys Ser Met523552405245gcc ctc gcg ggt ggc gtc acg gtg atg tca acc ccg gcc ggg ttc gtg 15846Ala Leu Ala Gly Gly Val Thr Val Met Ser Thr Pro Ala Gly Phe Val525052555260gag ttt tcg cgg cag cgg ggc ctg gcc gtg gac ggg cgg tgc aag gcg 15894Glu Phe Ser Arg Gln Arg Gly Leu Ala Val Asp Gly Arg Cys Lys Ala5265 527052755280ttc tcg gca gcg gct gac ggc acc ggc tgg ggt gag ggt gtc gga atg 15942Phe Ser Ala Ala Ala Asp Gly Thr Gly Trp Gly Glu Gly Val Gly Met528552905295ctg ctg gtg gag cgg ctg tcg gac gcg cgg cgg ctc ggt cac cga atc 15990Leu Leu Val Glu Arg Leu Ser Asp Ala Arg Arg Leu Gly His Arg Ile530053055310ctc gcg gtg gtg cgt ggc agt gcg gtc aat cag gac ggt gcg agc aac 16038Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn531553205325ggg ctg acg gcg ccc aac ggg ccg tcc cag gag cgt gtc atc cgc ctg 16086Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Glu Arg Val Ile Arg Leu533053355340gcc ctg gcc aac gcg gac ctg acc ccc gcc gac gtc gat gcg gtg gag 16134Ala Leu Ala Asn Ala Asp Leu Thr Pro Ala Asp Val Asp Ala Val Glu5345 535053555360gcc cac ggc acc ggc acc act ttg ggc gac ccg atc gag gcc cag gcc 16182Ala His Gly Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala536553705375ctc ctc gcc acc tac gga cag gac cgc ccc ggc aac gaa ccg ctg tgg 16230Leu Leu Ala Thr Tyr Gly Gln Asp Arg Pro Gly Asn Glu Pro Leu Trp538053855390ctg ggc tcg atg aag tcg aac atc ggc cac gcg cag gct gcc gca ggt 16278Leu Gly Ser Met Lys Ser Asn Ile Gly His Ala Gln Ala Ala Ala Gly539554005405gtg ggc ggg gtc atc aag atg gtg atg gcg ctg cgg aat ggt ctg ctg 16326Val Gly Gly Val Ile Lys Met Val Met Ala Leu Arg Asn Gly Leu Leu541054155420ccg cgg acg ttg cat gtg gat gag ccg tcg ccg cat gtg gac tgg tcc 16374Pro Arg Thr Leu His Val Asp Glu Pro Ser Pro His Val Asp Trp Ser5425 543054355440gcg ggg gcg gtg cag ctg ctg acg gag acg gtg ccc tgg ccc ggc ggg 16422Ala Gly Ala Val Gln Leu Leu Thr Glu Thr Val Pro Trp Pro Gly Gly544554505455gag ggg cgg ctg cgg cgg gca gga gtg tca tcg ttc ggc gtc agc ggc 16470Glu Gly Arg Leu Arg Arg Ala Gly Val Ser Ser Phe Gly Val Ser Gly546054655470acc aac gcc cac gtc atc ctc gaa gaa gca ccc gcc cac aac atc ccg 16518Thr Asn Ala His Val Ile Leu Glu Glu Ala Pro Ala His Asn Ile Pro547554805485tca gac aca ccc gcc gac gac gcc ccg gga gaa gca gcc gcc gac gat 16566Ser Asp Thr Pro Ala Asp Asp Ala Pro Gly Glu Ala Ala Ala Asp Asp549054955500gtt ccg ggg gaa gcg gcc ggc gac gac gcc ggt acc ggc ggg gaa gcg 16614Val Pro Gly Glu Ala Ala Gly Asp Asp Ala Gly Thr Gly Gly Glu Ala5505 551055155520act ggt cct gct gcc ggc agt cca ggg gtg tgg ccg tgg ctg gtg tcg 16662Thr Gly Pro Ala Ala Gly Ser Pro Gly Val Trp Pro Trp Leu Val Ser552555305535gcc aag tcg cag ccg gcc ctg cgc gcc cag gcc cag gcc ctg cac gcc 16710Ala Lys Ser Gln Pro Ala Leu Arg Ala Gln Ala Gln Ala Leu His Ala554055455550cac ctc acc gac cac ccc ggc ctc gac ctc gcc gac gtc ggg tac acc 16758His Leu Thr Asp His Pro Gly Leu Asp Leu Ala Asp Val Gly Tyr Thr555555605565ctc gcc cac gcc cgc gcc gtg ttc gac cac cgc gcc acc ctc atc gcc 16806Leu Ala His Ala Arg Ala Val Phe Asp His Arg Ala Thr Leu Ile Ala557055755580gcc gac cgc gac acc ttc ctg caa gca ctc cag gca ctc gcc gca ggc 16854Ala Asp Arg Asp Thr Phe Leu Gln Ala Leu Gln Ala Leu Ala Ala Gly5585 559055955600gaa ccc cac ccc gcc gtc atc cac agc agc gcc cca ggc ggg acc ggg 16902Glu Pro His Pro Ala Val Ile His Ser Ser Ala Pro Gly Gly Thr Gly560556105615acc ggg gag gcc gca gga aag acc gca ttc atc tgc tcc gga cag ggc 16950Thr Gly Glu Ala Ala Gly Lys Thr Ala Phe Ile Cys Ser Gly Gln Gly562056255630acc caa cgc ccc ggc atg gcc cac ggc ctc tac cac acc cac ccc gtc 16998Thr Gln Arg Pro Gly Met Ala His Gly Leu Tyr His Thr His Pro Val563556405645ttc gcc gcc gca ctc aac gac atc tgc acc cac ctc gac ccc cac ctc 17046Phe Ala Ala Ala Leu Asn Asp Ile Cys Thr His Leu Asp Pro His Leu565056555660gac cac ccc ctc ctc ccc ctc ctc acc cag gac ccc aac acc cag gac 17094Asp His Pro Leu Leu Pro Leu Leu Thr Gln Asp Pro Asn Thr Gln Asp5665 567056755680acc acc acc ctc gaa gaa gcg gcc gca ctg ctc cag cag acc ccg tac 17142Thr Thr Thr Leu Glu Glu Ala Ala Ala Leu Leu Gln Gln Thr Pro Tyr568556905695gcc cag ccc gcc ctc ttc gcc ttc cag gtc gcc ctc cac cgc ctc ctc 17190Ala Gln Pro Ala Leu Phe Ala Phe Gln Val Ala Leu His Arg Leu Leu570057055710acc gac ggc tac cac atc acc ccc cac tac tac gcc gga cac tcc ctc 17238Thr Asp Gly Tyr His Ile Thr Pro His Tyr Tyr Ala Gly His Ser Leu571557205725ggc gaa atc acc gcc gcc cac ctc gcc ggc atc ctc acc ctc acc gac 17286Gly Glu Ile Thr Ala Ala His Leu Ala Gly Ile Leu Thr Leu Thr Asp573057355740gcc acc acc ctc atc acc caa cgc gcc acc ctc atg caa acc atg ccc 17334Ala Thr Thr Leu Ile Thr Gln Arg Ala Thr Leu Met Gln Thr Met Pro5745 575057555760ccc ggc acc atg acc acc ctc cac acc acc ccc cac cac atc acc cac 17382Pro Gly Thr Met Thr Thr Leu His Thr Thr Pro His His Ile Thr His576557705775cac ctc acc gcc cac gaa aac gac ctc gcc atc gcc gcc atc aac acc 17430His Leu Thr Ala His Glu Asn Asp Leu Ala Ile Ala Ala Ile Asn Thr578057855790ccc acc tcc ctc gtc atc agc ggc acc ccc cac acc gtc caa cac atc 17478Pro Thr Ser Leu Val Ile Ser Gly Thr Pro His Thr Val Gln His Ile579558005805acc acc ctc tgc caa caa caa ggc atc aaa acc aaa acc ctc ccc acc 17526Thr Thr Leu Cys Gln Gln Gln Gly Ile Lys Thr Lys Thr Leu Pro Thr581058155820aaa aac gcc ttc cac tcc ccc cac acc aac ccc atc ctc aac caa ctc 17574Lys Asn Ala Phe His Ser Pro His Thr Asn Pro Ile Leu Asn Gln Leu5825 583058355840cac cag cac acc caa acc ctc acc tac cac cca ccc cac acc ccc ctc 17622His Gln His Thr Gln Thr Leu Thr Tyr His Pro Pro His Thr Pro Leu584558505855atc acc gcc aac acc cca ccc gac caa ctc ctc acc ccc cac tac tgg 17670Ile Thr Ala Asn Thr Pro Pro Asp Gln Leu Leu Thr Pro His Tyr Trp586058655870acc caa caa gcc cgc aac acc gtc gac tac gcc acc acc acc caa acc 17718Thr Gln Gln Ala Arg Asn Thr Val Asp Tyr Ala Thr Thr Thr Gln Thr587558805885ctc cac caa cac ggc gtc acc acc tac atc gaa ctc gga ccc gac aac 17766Leu His Gln His Gly Val Thr Thr Tyr Ile Glu Leu Gly Pro Asp Asn589058955900acc ctc acc acc ctc acc cac cac aac ctc ccc aac acc ccc acc acc 17814Thr Leu Thr Thr Leu Thr His His Asn Leu Pro Asn Thr Pro Thr Thr5905 591059155920acc ctc acc ctc acc cac ccc cac cac cac ccc caa acc cac ctc ctc 17862Thr Leu Thr Leu Thr His Pro His His His Pro Gln Thr His Leu Leu592559305935acc aac ctc gcc aaa acc acc acc acc tgg cac ccc cac cac tac acc 17910Thr Asn Leu Ala Lys Thr Thr Thr Thr Trp His Pro His His Tyr Thr594059455950cac cac cac aac caa ccc cac acc cac acc cac ctc gac ctc ccc acc 17958His His His Asn Gln Pro His Thr His Thr His Leu Asp Leu Pro Thr595559605965tac ccc ttc caa cac cag cac tac tgg ctc gaa agc aca cag ccg ggt 18006Tyr Pro Phe Gln His Gln His Tyr Trp Leu Glu Ser Thr Gln Pro Gly597059755980gcc gga tcc ggt tcg ggt tcc ggt tcc ggg cgg gca ggg act gcg ggc 18054Ala Gly Ser Gly Ser Gly Ser Gly Ser Gly Arg Ala Gly Thr Ala Gly5985 599059956000ggg acg gca gag gtg gag tcg cgg ttc tgg gac gcg gtg gcc cgc cag 18102Gly Thr Ala Glu Val Glu Ser Arg Phe Trp Asp Ala Val Ala Arg Gln600560106015gac ctg gaa acg gtc gcg acc acg ctc gcc gtg ccc ccc tcc gcc ggc 18150Asp Leu Glu Thr Val Ala Thr Thr Leu Ala Val Pro Pro Ser Ala Gly602060256030ctg gac acg gtg gtg ccc gca ctc tcc gcc tgg cac cgc cac caa cac 18198Leu Asp Thr Val Val Pro Ala Leu Ser Ala Trp His Arg His Gln His603560406045gac caa gcc cgc atc aac acc tgg acc tac cag gaa acc tgg aaa ccc 18246Asp Gln Ala Arg Ile Asn Thr Trp Thr Tyr Gln Glu Thr Trp Lys Pro605060556060ctc acc ctc ccc acc acc cac caa ccc cac caa acc tgg ctc atc gcc 18294Leu Thr Leu Pro Thr Thr His Gln Pro His Gln Thr Trp Leu Ile Ala6065 607060756080atc ccc gaa acc cag acc cac cac ccc cac atc acc aac atc ctc acc 18342Ile Pro Glu Thr Gln Thr His His Pro His Ile Thr Asn Ile Leu Thr608560906095aac ctc cac cac cac ggc atc acc ccc atc ccc ctc acc ctc aac cac 18390Asn Leu His His His Gly Ile Thr Pro Ile Pro Leu Thr Leu Asn His610061056110acc cac acc aac ccc caa cac ctc cac cac acc cga caa caa gcc caa 18438Thr His Thr Asn Pro Gln His Leu His His Thr Arg Gln Gln Ala Gln611561206125aac cac acc acc gga ccc atc acc ggc ctg ctc tcc ctc ctc gcc ctc 18486Asn His Thr Thr Gly Pro Ile Thr Gly Leu Leu Ser Leu Leu Ala Leu613061356140gac gaa aca ccc cac ccc cac cac ccc cac aca ccc acc ggc acc ctc 18534Asp Glu Thr Pro His Pro His His Pro His Thr Pro Thr Gly Thr Leu6145 615061556160ctc aac ctc acc ctc acc caa acc cac acc caa acc cac cca cca acc 18582Leu Asn Leu Thr Leu Thr Gln Thr His Thr Gln Thr His Pro Pro Thr616561706175ccc ctc tgg tac gcc acc acc aac gcc acc acc acc cac ccc aac gac 18630Pro Leu Trp Tyr Ala Thr Thr Asn Ala Thr Thr Thr His Pro Asn Asp618061856190ccc ctc aca cac ccc acc caa gcc caa acc tgg gga ctc gcc cgc acc 18678Pro Leu Thr His Pro Thr Gln Ala Gln Thr Trp Gly Leu Ala Arg Thr619562006205acc ctc ctc gaa cac ccc acc cac acc gcc gga atc atc gac ctc ccc 18726Thr Leu Leu Glu His Pro Thr His Thr Ala Gly Ile Ile Asp Leu Pro621062156220acc acc ccc acc ccc cac acc ctc cac cac ctc acc caa acc ctc acc 18774Thr Thr Pro Thr Pro His Thr Leu His His Leu Thr Gln Thr Leu Thr6225 623062356240caa ccc cac cac caa acc caa ctc gcc atc cgc acc acc ggc acc cac 18822Gln Pro His His Gln Thr Gln Leu Ala Ile Arg Thr Thr Gly Thr His624562506255acc cgc cgc ctc acc ccc acc acc ctc acc ccc aca cac caa cca ccc 18870Thr Arg Arg Leu Thr Pro Thr Thr Leu Thr Pro Thr His Gln Pro Pro626062656270acc ccc acc ccc cac gga acc acc ctc atc acc ggc gga acc ggc gcc 18918Thr Pro Thr Pro His Gly Thr Thr Leu Ile Thr Gly Gly Thr Gly Ala627562806285ctc gcc acc cac ctc acc cac cac ctc acc acc cac caa ccc acc caa 18966Leu Ala Thr His Leu Thr His His Leu Thr Thr His Gln Pro Thr Gln629062956300cac ctc ctc ctc acc agc cga acc ggc ccc cac acc ccc cac gca caa 19014His Leu Leu Leu Thr Ser Arg Thr Gly Pro His Thr Pro His Ala Gln6305 631063156320cac ctc acc acc caa ctc caa caa aaa ggc atc cac ctc acc atc acc 19062His Leu Thr Thr Gln Leu Gln Gln Lys Gly Ile His Leu Thr Ile Thr632563306335acc tgc gac acc agc aac cca gac caa ctc caa caa ctc ctc aac acc 19110Thr Cys Asp Thr Ser Asn Pro Asp Gln Leu Gln Gln Leu Leu Asn Thr634063456350atc ccc cca caa cac ccc ctc acc acc gtc atc cac acc gca ggc atc 19158Ile Pro Pro Gln His Pro Leu Thr Thr Val Ile His Thr Ala Gly Ile635563606365ctc gac gac gcc acc ctc acc aac ctc acc ccc acc caa ctc aac aac 19206Leu Asp Asp Ala Thr Leu Thr Asn Leu Thr Pro Thr Gln Leu Asn Asn637063756380gtc ctc cgc gcc aaa gcc cac agc gcc cac ctc ctc cac caa ctc acc 19254Val Leu Arg Ala Lys Ala His Ser Ala His Leu Leu His Gln Leu Thr6385 639063956400caa cac acc ccc ctc aac gcc ttc gtc ctc tac tcc tcc gcc gcc gcc 19302Gln His Thr Pro Leu Asn Ala Phe Val Leu Tyr Ser Ser Ala Ala Ala640564106415acc ttc ggc gca ccc ggc caa gcc aac tac gcc gca gcc aac gcc tac 19350Thr Phe Gly Ala Pro Gly Gln Ala Asn Tyr Ala Ala Ala Asn Ala Tyr642064256430ctc gac gcc ctc gcc cac cac cgc cac acc cac cac ctc ccc gcc acc 19398Leu Asp Ala Leu Ala His His Arg His Thr His His Leu Pro Ala Thr643564406445agc atc gcc tgg ggc acc tgg caa gga aac gga ctg gcg act ggt caa 19446Ser Ile Ala Trp Gly Thr Trp Gln Gly Asn Gly Leu Ala Thr Gly Gln645064556460gtc agc gaa cat ctc cgc cgc cgc ggg atg ttc gcc atg ccg ccc gag 19494Val Ser Glu His Leu Arg Arg Arg Gly Met Phe Ala Met Pro Pro Glu6465 647064756480ttg gcg gtc aca gct gtt gac ggc gcg atc gcg agc ggg cgc ccg agt 19542Leu Ala Val Thr Ala Val Asp Gly Ala Ile Ala Ser Gly Arg Pro Ser648564906495ctc ctc gtc gcc gat atc gac tgg aag aaa ttg gga ccg gtt ctc tcc 19590Leu Leu Val Ala Asp Ile Asp Trp Lys Lys Leu Gly Pro Val Leu Ser650065056510agc aag tcg tcg gtc ttg ctc gag gac ctt ccc cag gca cag gga act 19638Ser Lys Ser Ser Val Leu Leu Glu Asp Leu Pro Gln Ala Gln Gly Thr651565206525gag gag gcg cgc agt acc gtt gag cag acg gag agc aca aac ctc cgg 19686Glu Glu Ala Arg Ser Thr Val Glu Gln Thr Glu Ser Thr Asn Leu Arg653065356540caa ctc ctc atg ggt cgg tca cgt tcc gag cag gaa gaa gag ctg ctc 19734Gln Leu Leu Met Gly Arg Ser Arg Ser Glu Gln Glu Glu Glu Leu Leu6545 655065556560agc ctc gtc cgc atc cac tcc gcg gca gtg ctc ggg cgc gac gac tcc 19782Ser Leu Val Arg Ile His Ser Ala Ala Val Leu Gly Arg Asp Asp Ser656565706575gag gcc atc ccg ccc ggt cgg ctg ttc agg gat cta ggg ttc gac tcg 19830Glu Ala Ile Pro Pro Gly Arg Leu Phe Arg Asp Leu Gly Phe Asp Ser658065856590ctt gcg gcg gtg gag ctt cgc aac cac ctc gca gca cag acg gag ctg 19878Leu Ala Ala Val Glu Leu Arg Asn His Leu Ala Ala Gln Thr Glu Leu659566006605gct ctg ccg acg act ctc gtc ttc gat tac ccc agc ccc acc aag ctc 19926Ala Leu Pro Thr Thr Leu Val Phe Asp Tyr Pro Ser Pro Thr Lys Leu661066156620gcc caa ttt ctg ctc tcc gag atc gcg gag ttc cag ccc gac aac tca 19974Ala Gln Phe Leu Leu Ser Glu Ile Ala Glu Phe Gln Pro Asp Asn Ser6625 663066356640act ccg ctt ccg cga ccc cgg gca gag ctc gat gag ccg atc gcc atc 20022Thr Pro Leu Pro Arg Pro Arg Ala Glu Leu Asp Glu Pro Ile Ala Ile664566506655gtt ggc atg gcc tgt cgc ttc ccc ggc gga gtg acc tcg gcg gac gac 20070Val Gly Met Ala Cys Arg Phe Pro Gly Gly Val Thr Ser Ala Asp Asp666066656670ttc tgg gat ctg atc tcc tcc gag cag gac gcg atc ggc gga ttc ccc 20118Phe Trp Asp Leu Ile Ser Ser Glu Gln Asp Ala Ile Gly Gly Phe Pro667566806685acc gac cgc ggc tgg gac ctg gac acg ctc tac gac ccc gac ccc gac 20166Thr Asp Arg Gly Trp Asp Leu Asp Thr Leu Tyr Asp Pro Asp Pro Asp669066956700cac ccc ggc acc tgc tac acc cga aac ggc gga ttc ctc tac gac gca 20214His Pro Gly Thr Cys Tyr Thr Arg Asn Gly Gly Phe Leu Tyr Asp Ala6705 671067156720ggc cac ttc gac gcc gaa ttc ttc ggc atc agc ccc cgc gaa gcc ctc 20262Gly His Phe Asp Ala Glu Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu672567306735gcc atg gac ccc cag caa cga ctc ctc ctc gaa acc gcc tgg gaa acc 20310Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Thr Ala Trp Glu Thr674067456750atc gaa cac gcc ggc atc aac ccc cac acc ctc cac ggc acc ccc acc 20358Ile Glu His Ala Gly Ile Asn Pro His Thr Leu His Gly Thr Pro Thr675567606765gga gtc ttc acc ggc acc aac gga cag gac cac gcg gca cac atc cgt 20406Gly Val Phe Thr Gly Thr Asn Gly Gln Asp His Ala Ala His Ile Arg677067756780cag gcc ccg agc ggt acc gag gga ttc gtc ctg acc ggg gca gcc acc 20454Gln Ala Pro Ser Gly Thr Glu Gly Phe Val Leu Thr Gly Ala Ala Thr6785 679067956800agc atc gcc tcc ggc cga atc tcc tac atc ctc ggg ttg gaa ggg cct 20502Ser Ile Ala Ser Gly Arg Ile Ser Tyr Ile Leu Gly Leu Glu Gly Pro680568106815gcg gtc acc ctc gac aca gcg tgt tcc tcc tcg ctc gtc gcc ctg cac 20550Ala Val Thr Leu Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His682068256830ctc gcc tgc cag tcc ctc agg tcc ggt gaa tgc acc atg gcc ttg gcc 20598Leu Ala Cys Gln Ser Leu Arg Ser Gly Glu Cys Thr Met Ala Leu Ala683568406845ggc ggg gcc acg gtc atg acc acc ccg atc acc ttc acc gaa ttc gcc 20646Gly Gly Ala Thr Val Met Thr Thr Pro Ile Thr Phe Thr Glu Phe Ala685068556860cgc caa cgc gga ctc gcc ccc gac ggg cgt tgc aag gcg ttc tcg gcg 20694Arg Gln Arg Gly Leu Ala Pro Asp Gly Arg Cys Lys Ala Phe Ser Ala6865 687068756880gcg gct gac ggt acc ggc tgg ggt gag ggt gtg ggg atg ctg ctg gtg 20742Ala Ala Asp Gly Thr Gly Trp Gly Glu Gly Val Gly Met Leu Leu Val688568906895gag cgg ctc tcc gac gcc cgc cgc aac ggt cac cgt gtc ctg gcc gtg 20790Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly His Arg Val Leu Ala Val690069056910gtg cgt ggc agt gcg gtc aac cag gac ggt gcg agc aac ggt ctg acc 20838Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr691569206925gcg ccc aac ggg ccc tcc cag cag cgc gtc atc cgc cag gcc ctc gcc 20886Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala693069356940aac gcg gac ctg acc ccc gcc gac gtc gat gcg gtg gag gcc cac ggc 20934Asn Ala Asp Leu Thr Pro Ala Asp Val Asp Ala Val Glu Ala His Gly6945 695069556960acc ggc acc act ttg ggc gac ccg atc gag gcc cag gcc atc ctc gcg 20982Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala Ile Leu Ala696569706975acc tac gga cag gac cgt ccc ggc aac ggg ccg ttg tgg ctg ggc tcc 21030Thr Tyr Gly Gln Asp Arg Pro Gly Asn Gly Pro Leu Trp Leu Gly Ser698069856990gtc aag tcc aac gtc gga cac aca cag gcc gcg gcg ggc gtg gcc gga 21078Val Lys Ser Asn Val Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly699570007005gtg atc aag atg gtg atg gcc ctc cgc cac cgg aca ctc cca ccg act 21126Val Ile Lys Met Val Met Ala Leu Arg His Arg Thr Leu Pro Pro Thr701070157020ctc cac gcg gat gag ccg tcg ccg cat gtg gac tgg tcc gcg ggt gcg 21174Leu His Ala Asp Glu Pro Ser Pro His Val Asp Trp Ser Ala Gly Ala7025 703070357040gtg cag ctg ctg acg gag acg gtg ccc tgg ccc ggc ggg gag ggg cgg 21222Val Gln Leu Leu Thr Glu Thr Val Pro Trp Pro Gly Gly Glu Gly Arg704570507055ccg cgg cgg gca gga gtg tca tca ttc ggc gtc agc ggc acc aac gcc 21270Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Val Ser Gly Thr Asn Ala706070657070cac gtc atc ctc gaa gaa gca ccc gcc gac gac gtt ccg ggg gga cca 21318His Val Ile Leu Glu Glu Ala Pro Ala Asp Asp Val Pro Gly Gly Pro707570807085ccc gcc gac gag gat gcc ggt agt ggc gag gag gct gct gcc ggc agt 21366Pro Ala Asp Glu Asp Ala Gly Ser Gly Glu Glu Ala Ala Ala Gly Ser709070957100cct ggg gtg tgg ccg tgg ctg gtg tcg gcc aag tcg cag ccg gcc ctg 21414Pro Gly Val Trp Pro Trp Leu Val Ser Ala Lys Ser Gln Pro Ala Leu7105 711071157120cgc gcc cag gcc cag gcc ctg cac gcc cac ctc acc gac cac ccc ggc 21462Arg Ala Gln Ala Gln Ala Leu His Ala His Leu Thr Asp His Pro Gly712571307135ctc gac ctc gcc gac gtc gga tac acc ctc gcc cac gcc cgc gcc gtg 21510Leu Asp Leu Ala Asp Val Gly Tyr Thr Leu Ala His Ala Arg Ala Val714071457150ttc gac cac cgc gcc acc ctc atc gcc gcc gac cgc gac acc ttc ctg 21558Phe Asp His Arg Ala Thr Leu Ile Ala Ala Asp Arg Asp Thr Phe Leu715571607165caa gca ctc cag gca ctc gcc gca ggc gaa ccc cac ccc gcc gtc atc 21606Gln Ala Leu Gln Ala Leu Ala Ala Gly Glu Pro His Pro Ala Val Ile717071757180cac agc agc gcc cca ggc ggg acc ggg acc ggg gag gcc gca gga aag 21654His Ser Ser Ala Pro Gly Gly Thr Gly Thr Gly Glu Ala Ala Gly Lys7185 719071957200acc gca ttc atc tgc tcc gga cag ggc acc caa cgc ccc ggc atg gcc 21702Thr Ala Phe Ile Cys Ser Gly Gln Gly Thr Gln Arg Pro Gly Met Ala720572107215cac ggc ctc tac cac acc cac ccc gtc ttc gcc gcc gca ctc aac gac 21750His Gly Leu Tyr His Thr His Pro Val Phe Ala Ala Ala Leu Ash Asp722072257230atc tgc acc cac ctc gac ccc cac ctc gac cac ccc ctc ctc ccc ctc 21798Ile Cys Thr His Leu Asp Pro His Leu Asp His Pro Leu Leu Pro Leu723572407245ctc acc caa aac gac aac gac aac gac aac gag gac gcg gcc gca ctg 21846Leu Thr Gln Asn Asp Asn Asp Asn Asp Asn Glu Asp Ala Ala Ala Leu725072557260ctc cag cag acc ccg tac gcc cag ccc gcc ctc ttc gcc ttc cag gtc 21894Leu Gln Gln Thr Pro Tyr Ala Gln Pro Ala Leu Phe Ala Phe Gln Val7265 727072757280gcc ctc cac cgc ctc ctc acc gac ggc tac cac atc acc ccc cac tac 21942Ala Leu His Arg Leu Leu Thr Asp Gly Tyr His Ile Thr Pro His Tyr728572907295tac gcc gga cac tcc ctc ggc gaa atc acc gcc gcc cac ctc gcc ggc 21990Tyr Ala Gly His Ser Leu Gly Glu Ile Thr Ala Ala His Leu Ala Gly730073057310atc ctc acc ctc acc gac gcc acc acc ctc atc acc caa cgc gcc acc 22038Ile Leu Thr Leu Thr Asp Ala Thr Thr Leu Ile Thr Gln Arg Ala Thr731573207325ctc atg caa acc atg ccc ccc ggc acc atg acc acc ctc cac acc acc 22086Leu Met Gln Thr Met Pro Pro Gly Thr Met Thr Thr Leu His Thr Thr733073357340cca cac cac atc acc cac cac ctc acc gcc cac gaa aac gac ctc gcc 22134Pro His His Ile Thr His His Leu Thr Ala His Glu Asn Asp Leu Ala7345 735073557360atc gcc gcc atc aac acc ccc acc tcc ctc gtc atc agc ggc acc ccc 22182Ile Ala Ala Ile Asn Thr Pro Thr Ser Leu Val Ile Ser Gly Thr Pro736573707375cac acc gtc caa cac atc acc acc ctc tgc caa caa caa ggc atc aaa 22230His Thr Val Gln His Ile Thr Thr Leu Cys Gln Gln Gln Gly Ile Lys738073857390acc aaa acc ctc ccc acc aac cac gcc ttc cac tcc ccc cac acc aac 22278Thr Lys Thr Leu Pro Thr Asn His Ala Phe His Ser Pro His Thr Asn739574007405ccc atc ctc aac caa ctc cac cag cac acc caa acc ctc acc tac cac 22326Pro Ile Leu Asn Gln Leu His Gln His Thr Gln Thr Leu Thr Tyr His741074157420cca ccc cac acc ccc ctc atc acc gcc aac acc cca ccc gac caa ctc 22374Pro Pro His Thr Pro Leu Ile Thr Ala Asn Thr Pro Pro Asp Gln Leu7425 743074357440ctc acc ccc cac tac tgg acc caa caa gcc cgc aac acc gtc gac tac 22422Leu Thr Pro His Tyr Trp Thr Gln Gln Ala Arg Asn Thr Val Asp Tyr744574507455gcc acc acc acc caa acc ctc cac caa cac ggc gtc acc acc tac atc 22470Ala Thr Thr Thr Gln Thr Leu His Gln His Gly Val Thr Thr Tyr Ile746074657470gaa ctc gga ccc gac aac acc ctc acc acc ctc acc cac cac aac ctc 22518Glu Leu Gly Pro Asp Asn Thr Leu Thr Thr Leu Thr His His Asn Leu747574807485ccc aac acc ccc acc acc acc ctc acc ctc acc cac ccc cac cac cac 22566Pro Asn Thr Pro Thr Thr Thr Leu Thr Leu Thr His Pro His His His749074957500ccc caa acc cac ctc ctc acc aac ctc gcc aaa acc acc acc acc tgg 22614Pro Gln Thr His Leu Leu Thr Asn Leu Ala Lys Thr Thr Thr Thr Trp7505 751075157520cac ccc cac cac tac acc cac cac cac aac caa ccc cac acc cac acc 22662His Pro His His Tyr Thr His His His Asn Gln Pro His Thr His Thr752575307535cac ctc gac ctc ccc acc tac ccc ttc caa cac cac cac tac tgg ctc 22710His Leu Asp Leu Pro Thr Tyr Pro Phe Gln His His His Tyr Trp Leu754075457550gaa cta ccc agc gcc caa acc agc ccc ggt caa agg cgt tct cgc cgc 22758Glu Leu Pro Ser Ala Gln Thr Ser Pro Gly Gln Arg Arg Ser Arg Arg755575607565tcg gct cca gac acc gcc gag tcg gag ttc tgg gac gcg gtg aac gag 22806Ser Ala Pro Asp Thr Ala Glu Ser Glu Phe Trp Asp Ala Val Asn Glu757075757580gaa gac ctc cag agc ctc gcc gaa acc ctc gac atc gac gcc tct gct 22854Glu Asp Leu Gln Ser Leu Ala Glu Thr Leu Asp Ile Asp Ala Ser Ala7585 759075957600ctg gac acg gtg gtg ccc gca ctc tcc gcc tgg cac cgc cac caa cac 22902Leu Asp Thr Val Val Pro Ala Leu Ser Ala Trp His Arg His Gln His760576107615gac caa gcc cgc atc aac acc tgg acc tac cag gaa acc tgg aaa ccc 22950Asp Gln Ala Arg Ile Asn Thr Trp Thr Tyr Gln Glu Thr Trp Lys Pro762076257630ctc acc ctc ccc acc acc cac caa ccc cac caa acc tgg ctc atc gcc 22998Leu Thr Leu Pro Thr Thr His Gln Pro His Gln Thr Trp Leu Ile Ala763576407645atc ccc gaa acc cag acc cac cac ccc cac atc acc aac atc ctc acc 23046Ile Pro Glu Thr Gln Thr His His Pro His Ile Thr Asn Ile Leu Thr765076557660aac ctc cac cac cac ggc atc acc ccc atc ccc ctc act gtc aac cac 23094Asn Leu His His His Gly Ile Thr Pro Ile Pro Leu Thr Val Asn His7665 767076757680acc cac acc aac ccc caa cac ctc cac cac acc ctc cac cac acc cga 23142Thr His Thr Asn Pro Gln His Leu His His Thr Leu His His Thr Arg768576907695caa caa gcc caa aac cac acc acc gga ccc atc acc ggc ctg ctc tcc 23190Gln Gln Ala Gln Asn His Thr Thr Gly Pro Ile Thr Gly Leu Leu Ser770077057710ctc ctc gcc ctc gac gaa aca ccc cac ccc cac cac ccc cac aca ccc 23238Leu Leu Ala Leu Asp Glu Thr Pro His Pro His His Pro His Thr Pro771577207725acc ggc acc ctc ctc aac ctc acc ctc ccc caa acc cac acc caa acc 23286Thr Gly Thr Leu Leu Asn Leu Thr Leu Pro Gln Thr His Thr Gln Thr773077357740cac cca cca acc ccc ctc tgg tac gcc acc acc aac gcc acc acc acc 23334His Pro Pro Thr Pro Leu Trp Tyr Ala Thr Thr Asn Ala Thr Thr Thr7745 775077557760cac ccc aac gac ccc ctc aca cac ccc acc caa gcc caa acc tgg gga 23382His Pro Asn Asp Pro Leu Thr His Pro Thr Gln Ala Gln Thr Trp Gly776577707775ctc gcc cgc acc acc ctc ctc gaa cac ccc acc cac acc gcc gga atc 23430Leu Ala Arg Thr Thr Leu Leu Glu His Pro Thr His Thr Ala Gly Ile778077857790atc gac ctc ccc acc acc ccc acc ccc cac acc ctc cac cac ctc acc 23478Ile Asp Leu Pro Thr Thr Pro Thr Pro His Thr Leu His His Leu Thr779578007805caa acc ctc acc caa ccc cac cac caa acc caa ctc gcc atc cgc acc 23526Gln Thr Leu Thr Gln Pro His His Gln Thr Gln Leu Ala Ile Arg Thr781078157820acc ggc acc cac acc cgc cgc ctc acc ccc acc acc ctc acc ccc aca 23574Thr Gly Thr His Thr Arg Arg Leu Thr Pro Thr Thr Leu Thr Pro Thr7825 783078357840cac caa cca ccc acc ccc acc ccc cac gga acc acc ctc atc acc ggc 23622His Gln Pro Pro Thr Pro Thr Pro His Gly Thr Thr Leu Ile Thr Gly784578507855gga acc ggc gcc ctc gcc acc cac ctc acc cac cac ctc acc acc cac 23670Gly Thr Gly Ala Leu Ala Thr His Leu Thr His His Leu Thr Thr His786078657870caa ccc acc caa cac ctc ctc ctc acc agc cga acc ggc ccc cac acc 23718Gln Pro Thr Gln His Leu Leu Leu Thr Ser Arg Thr Gly Pro His Thr787578807885ccc cac gca caa cac ctc acc acc caa ctc caa caa aaa ggc atc cac 23766Pro His Ala Gln His Leu Thr Thr Gln Leu Gln Gln Lys Gly Ile His789078957900ctc acc atc acc acc tgc gac acc agc aac cca gac caa ctc caa caa 23814Leu Thr Ile Thr Thr Cys Asp Thr Ser Asn Pro Asp Gln Leu Gln Gln7905 791079157920ctc ctc aac acc atc ccc cca caa cac ccc ctc acc acc gtc atc cac 23862Leu Leu Asn Thr Ile Pro Pro Gln His Pro Leu Thr Thr Val Ile His792579307935acc gca ggc gtc aat ctc ttc gcc ccc gtg tcg gaa acc gat gcc gaa 23910Thr Ala Gly Val Asn Leu Phe Ala Pro Val Ser Glu Thr Asp Ala Glu794079457950tcc ttc tct tcc gtt acg gca gcg aag gca acg ggc gcg gcg att ctg 23958Ser Phe Ser Ser Val Thr Ala Ala Lys Ala Thr Gly Ala Ala Ile Leu795579607965cat gag ttg ctg ctg gac cat gaa acg ctt gaa cac ttc att ctc ttc 24006His Glu Leu Leu Leu Asp His Glu Thr Leu Glu His Phe Ile Leu Phe797079757980tcg tcg ggc gcc ggc gct tgg ggc agc ggg aat cag tgc gca tac tcg 24054Ser Ser Gly Ala Gly Ala Trp Gly Ser Gly Asn Gln Cys Ala Tyr Ser7985 799079958000gcg gcc aac gca tac ctg gac gcg ctc gcg acg cat cgt cag aca cat 24102Ala Ala Asn Ala Tyr Leu Asp Ala Leu Ala Thr His Arg Gln Thr His800580108015gga ctt ccc ggg gca tcg atc gcc tgg ggc ccc tgg gcc gga aag ggc 24150Gly Leu Pro Gly Ala Ser Ile Ala Trp Gly Pro Trp Ala Gly Lys Gly802080258030atg tcg gcc ggt gat gcg gct cat ggt tac ctg gaa aag cgc ggc att 24198Met Ser Ala Gly Asp Ala Ala His Gly Tyr Leu Glu Lys Arg Gly Ile803580408045ctg ccg atg gag cca cgc atg gcg ctc gcg gca ttc cat cgt gcg cgg 24246Leu Pro Met Glu Pro Arg Met Ala Leu Ala Ala Phe His Arg Ala Arg805080558060gcg cag cgg ccg aat tcc aac ctg atc atc gcg gac atc gac tgg gag 24294Ala Gln Arg Pro Asn Ser Asn Leu Ile Ile Ala Asp Ile Asp Trp Glu8065 807080758080cgc ttc gtc ccc gcc ttc acc gct cga cgc cac agc ccg ctc atc gag 24342Arg Phe Val Pro Ala Phe Thr Ala Arg Arg His Ser Pro Leu Ile Glu808580908095gac att ccg gag gtt cgg caa gcg gct cag gag ctg gaa gca gct gcg 24390Asp Ile Pro Glu Val Arg Gln Ala Ala Gln Glu Leu Glu Ala Ala Ala810081058110tcg acg gca aag acg acc aca gct cag ccg att gcg acg tct ctc cgt 24438Ser Thr Ala Lys Thr Thr Thr Ala Gln Pro Ile Ala Thr Ser Leu Arg811581208125gag cga ttg gcc cga ctg acg tcc tca aag cag aac cag gtg ctg ctc 24486Glu Arg Leu Ala Arg Leu Thr Ser Ser Lys Gln Asn Gln Val Leu Leu813081358140ggc ctg att cgg aca ggc atc tgc acc gtt ctc ggc ctt cgt aat ccg 24534Gly Leu Ile Arg Thr Gly lle Cys Thr Val Leu Gly Leu Arg Asn Pro8145 815081558160gaa ggc atc gag gac caa cga gcc ttc cgc gac ctc ggc ttc gac tcg 24582Glu Gly Ile Glu Asp Gln Arg Ala Phe Arg Asp Leu Gly Phe Asp Ser816581708175ctg acg tcg gct cag ttc agc aag gaa ctc gcc aag gaa acc gga ctg 24630Leu Thr Ser Ala Gln Phe Ser Lys Glu Leu Ala Lys Glu Thr Gly Leu818081858190cca ctc ccc ccg tcc ctg gtc ttc gac tat ccc acc ccg cag gaa tgt 24678Pro Leu Pro Pro Ser Leu Val Phe Asp Tyr Pro Thr Pro Gln Glu Cys819582008205gct gcc cat ctg cgc aca caa ctc gtc gac cta gac gac gaa gag gac 24726Ala Ala His Leu Arg Thr Gln Leu Val Asp Leu Asp Asp Glu Glu Asp821082158220gcg gca ctg tcg aat gct ctc ccg caa gtg gcc cat cgg cgt acc gtc 24774Ala Ala Leu Ser Asn Ala Leu Pro Gln Val Ala His Arg Arg Thr Val8225 823082358240gag gac gaa ccg atc gcc atc atc ggt atg gca tgt cgc ttc ccc ggc 24822Glu Asp Glu Pro Ile Ala Ile Ile Gly Met Ala Cys Arg Phe Pro Gly824582508255ggc gta cgt tct gcc gac gac ctg tgg gaa ttg ctc gct tcg ggt aag 24870Gly Val Arg Ser Ala Asp Asp Leu Trp Glu Leu Leu Ala Ser Gly Lys826082658270gac gct atc ggc gtc ttc ccg acc gac cgc ggc tgg gac ctg gac acg 24918Asp Ala Ile Gly Val Phe Pro Thr Asp Arg Gly Trp Asp Leu Asp Thr827582808285ctc tac gac ccc gac ccc gac cac ccc ggc acc tgc tac acc cga aac 24966Leu Tyr Asp Pro Asp Pro Asp His Pro Gly Thr Cys Tyr Thr Arg Asn829082958300ggc gga ttc ctc tac ggc gca ggc cac ttc gac gcc gaa ttc ttc ggc 25014Gly Gly Phe Leu Tyr Gly Ala Gly His Phe Asp Ala Glu Phe Phe Gly8305 831083158320atc agc ccc cgc gaa gcc ctc gcc atg gac ccc cag caa cga ctc ctc 25062Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu832583308335ctc gaa acc gcc tgg gaa acc atc gaa cac gcc ggc atc aac ccc cac 25110Leu Glu Thr Ala Trp Glu Thr Ile Glu His Ala Gly Ile Asn Pro His834083458350acc ctc cac ggc acc ccc acc gga gtc ttc gcc gga atc aac gct caa 25158Thr Leu His Gly Thr Pro Thr Gly Val Phe Ala Gly Ile Asn Ala Gln835583608365gac cac gcc gcg cat atc cgc caa agc cgt gat gtg gag acc atc gag 25206Asp His Ala Ala His Ile Arg Gln Ser Arg Asp Val Glu Thr Ile Glu837083758380ggc tac gcc ctg acc ggc agt tcg gga agt gtg gcg tcc ggc cgg gtg 25254Gly Tyr Ala Leu Thr Gly Ser Ser Gly Ser Val Ala Ser Gly Arg Val8385 839083958400gcc tac acg ctc ggg ctc gaa ggc ccc gcg gtg tcg gtg gat acg gcg 25302Ala Tyr Thr Leu Gly Leu Glu Gly Pro Ala Val Ser Val Asp Thr Ala840584108415tgt tcg tcg tcg ttg gtg gcg ttg cat tgg gcg gcg cag gcg ttg cgt 25350Cys Ser Ser Ser Leu Val Ala Leu His Trp Ala Ala Gln Ala Leu Arg842084258430gcg ggt gag tgt tcg atg gcg ctt gcc ggg ggt gtg acg gtg atg tcg 25398Ala Gly Glu Cys Ser Met Ala Leu Ala Gly Gly Val Thr Val Met Ser843584408445tct ccg ggt acg ttt gtg gag ttc tca cgt cag cgg ggt ctg gcc gcg 25446Ser Pro Gly Thr Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Ala845084558460gac ggg cgg tgc aag gcc tat tcg gcg gct gct gac ggt acc ggc tgg 25494Asp Gly Arg Cys Lys Ala Tyr Ser Ala Ala Ala Asp Gly Thr Gly Trp8465 847084758480gcc gag ggt gtg ggg atg ctg ctg gtg gag cgg ctc tcc gac gcc cgt 25542Ala Glu Gly Val Gly Met Leu Leu Val Glu Arg Leu Ser Asp Ala Arg848584908495cgc aac ggt cac cgt gtc ctg gcc gtg gtg cgt ggc agt gcg gtc aac 25590Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn850085058510cag gac ggt gcg agc aac ggt ctg acc gcg ccc aac ggg ccc tcc cag 25638Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln851585208525cag cgt gtc atc cgt cag gcc ctg gcc aat gcg gga ctg acc ccg gcc 25686Gln Arg Val Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Thr Pro Ala853085358540gat gtc gac gca gtg gag ggc cac ggc acc ggg acc act ctg ggg gac 25734Asp Val Asp Ala Val Glu Gly His Gly Thr Gly Thr Thr Leu Gly Asp8545 855085558560ccg atc gag gcc cag gca ctc ctg gcc gcc tac gga caa cac cgc ccc 25782Pro Ile Glu Ala Gln Ala Leu Leu Ala Ala Tyr Gly Gln His Arg Pro856585708575cac cac cgc ccc ttg tgg ctg gga tcc ctc aaa tcc aac atc ggg cac 25830His His Arg Pro Leu Trp Leu Gly Ser Leu Lys Ser Asn Ile Gly His858085858590gca cag gcc gcc gcg ggc gtg ggc gga gtc atc aag atg gtg atg gcc 25878Ala Gln Ala Ala Ala Gly Val Gly Gly Val Ile Lys Met Val Met Ala859586008605ctg cgc aac ggg ctg ctg cca cag acc ctc cac gtg gac gag ccc acc 25926Leu Arg Asn Gly Leu Leu Pro Gln Thr Leu His Val Asp Glu Pro Thr861086158620ccc cag gtc gac tgg tcc aca ggc gca gta caa ctc ctg aca caa cct 25974Pro Gln Val Asp Trp Ser Thr Gly Ala Val Gln Leu Leu Thr Gln Pro8625 863086358640gtg ccc tgg ccc gcc gac ccg gcc ggc cgg cca cgc cac gcc ggc gtg 26022Val Pro Trp Pro Ala Asp Pro Ala Gly Arg Pro Arg His Ala Gly Val864586508655tca tca ttc ggc gtc agc ggc acc aac gcc cac atc atc ctc gaa gaa 26070Ser Ser Phe Gly Val Ser Gly Thr Asn Ala His Ile Ile Leu Glu Glu866086658670gca ccc act ccc cag gac agc gat acc gac gac gaa ccg cct gcc aac 26118Ala Pro Thr Pro Gln Asp Ser Asp Thr Asp Asp Glu Pro Pro Ala Asn867586808685gca cca gcc ctg ccc cat ccc ctc cct ctt ccc gtg ccg gtg tcg gcg 26166Ala Pro Ala Leu Pro His Pro Leu Pro Leu Pro Val Pro Val Ser Ala869086958700agg tct gag gcc ggg ttg cgg gcg cag gca cag gcg ttg cgc cag tac 26214Arg Ser Glu Ala Gly Leu Arg Ala Gln Ala Gln Ala Leu Arg Gln Tyr8705 871087158720gtg gca gcc cgc ccg gac atg tca cct gcc gac att ggt gcg ggt ctg 26262Val Ala Ala Arg Pro Asp Met Ser Pro Ala Asp Ile Gly Ala Gly Leu872587308735gcc cgc ggc cgg gcc gta ctg gaa cac cgc gcc gtc atc ctg gcc gcg 26310Ala Arg Gly Arg Ala Val Leu Glu His Arg Ala Val Ile Leu Ala Ala874087458750gac cgc gag gaa ctg gcg cag gca ctg aca gcc ctg gca gcc ggc gaa 26358Asp Arg Glu Glu Leu Ala Gln Ala Leu Thr Ala Leu Ala Ala Gly Glu875587608765ccc cac ccc cac atc acc aca ggc cac acc cgg ggc ggt gac cgc ggc 26406Pro His Pro His Ile Thr Thr Gly His Thr Arg Gly Gly Asp Arg Gly877087758780ggc gtc gtc ttc gtc ttc ccc gga cag ggc ggc cag tgg gcc ggg atg 26454Gly Val Val Phe Val Phe Pro Gly Gln Gly Gly Gln Trp Ala Gly Met8785 879087958800ggc ctg acc ctg ctc acc tcc tca ccc gtg ttc gcc gaa cac atc gac 26502Gly Leu Thr Leu Leu Thr Ser Ser Pro Val Phe Ala Glu His Ile Asp880588108815gca tgc gag aaa gcc ctc acc ccc tgg gtg ccc tgg tcc ctg acc gac 26550Ala Cys Glu Lys Ala Leu Thr Pro Trp Val Pro Trp Ser Leu Thr Asp882088258830atc ctg cac cgc gac ccc gac gac ccc gca tgg caa caa gcc gac gtg 26598Ile Leu His Arg Asp Pro Asp Asp Pro Ala Trp Gln Gln Ala Asp Val883588408845gtc cag ccc gtg ctc ttc agc atc atg gtc tcc ctc gcc gcc ctg tgg 26646Val Gln Pro Val Leu Phe Ser Ile Met Val Ser Leu Ala Ala Leu Trp885088558860cgc tcc tac ggc atc gaa ccc gac gcg gtc ctc ggc cac tcc cag gga 26694Arg Ser Tyr Gly Ile Glu Pro Asp Ala Val Leu Gly His Ser Gln Gly8865 887088758880gaa atc gcc gcc gcc cac atc tgc ggc gca ctc agc ctg aaa gac gcc 26742Glu Ile Ala Ala Ala His Ile Cys Gly Ala Leu Ser Leu Lys Asp Ala888588908895gcc aaa acc gtt gca ctg cgc agc cgc gca ctg gcc gcc gta cga ggc 26790Ala Lys Thr Val Ala Leu Arg Ser Arg Ala Leu Ala Ala Val Arg Gly890089058910cgg ggc gcc atg gcc tca ctg ccc ctg ccc gcc cag gac gtg cag cag 26838Arg Gly Ala Met Ala Ser Leu Pro Leu Pro Ala Gln Asp Val Gln Gln891589208925ctc att tcc gaa cgg tgg gaa ggg cag ttg tgg gtg gca gcc ctc aac 26886Leu Ile Ser Glu Arg Trp Glu Gly Gln Leu Trp Val Ala Ala Leu Asn893089358940ggc ccc cac tcc acc acc gtc tcc ggc gac acc aag gcg gtg gat gag 26934Gly Pro His Ser Thr Thr Val Ser Gly Asp Thr Lys Ala Val Asp Glu8945 895089558960gtg ctg gcg cac tgc acc gac acc ggc cta cgg gcc aaa cgc atc ccc 26982Val Leu Ala His Cys Thr Asp Thr Gly Leu Arg Ala Lys Arg Ile Pro896589708975gtc gac tac gcc tcc cac tgc ccc cac gtc caa ccc ctc cac gac gaa 27030Val Asp Tyr Ala Ser His Cys Pro His Val Gln Pro Leu His Asp Glu898089858990ctc ctg cac ctg ctg gga gac atc acc ccc cag ccg tcc acc gtg ccg 27078Leu Leu His Leu Leu Gly Asp Ile Thr Pro Gln Pro Ser Thr Val Pro899590009005ttc ttc tcc acc gtg gaa ggc acc tgg ctg gac acc aca acc ctg gac 27126Phe Phe Ser Thr Val Glu Gly Thr Trp Leu Asp Thr Thr Thr Leu Asp901090159020gcc gcc tac tgg tac cgc aac ctc cac cag ccc gtc cgc ttc agc cac 27174Ala Ala Tyr Trp Tyr Arg Asn Leu His Gln Pro Val Arg Phe Ser His9025 903090359040gcc atc cag acc ctg acc gac gac gga cac cgc gcc ttc atc gaa atc 27222Ala Ile Gln Thr Leu Thr Asp Asp Gly His Arg Ala Phe Ile Glu Ile904590509055agc ccc cac ccc acc ctc gtc ccc gcc atc gaa gac acc acc gaa aac 27270Ser Pro His Pro Thr Leu Val Pro Ala Ile Glu Asp Thr Thr Glu Asn906090659070acc acc gaa aac atc acc gcg acc ggc agc ctc cgc cgc ggc gac aac 27318Thr Thr Glu Asn Ile Thr Ala Thr Gly Ser Leu Arg Arg Gly Asp Asn907590809085gac acc cac cgc ttc ctc acc gcc ctc gcc cac acc cac acc acc ggc 27366Asp Thr His Arg Phe Leu Thr Ala Leu Ala His Thr His Thr Thr Gly909090959100atc ggc aca ccc acc acc tgg cac cac cac tac acc caa acc cac ccc 27414Ile Gly Thr Pro Thr Thr Trp His His His Tyr Thr Gln Thr His Pro9105 911091159120cac ccc aac ccc cac acc cac ctc gac ctg ccc acc tac ccc ttc caa 27462His Pro Asn Pro His Thr His Leu Asp Leu Pro Thr Tyr Pro Phe Gln912591309135cac cag cac tac tgg ctc caa cca ccc acc aca aca acc gac ctc acc 27510His Gln His Tyr Trp Leu Gln Pro Pro Thr Thr Thr Thr Asp Leu Thr914091459150acc acc ggc ctc acc ccc acc cac cac ccc ctc ctc acc gcc aca ctc 27558Thr Thr Gly Leu Thr Pro Thr His His Pro Leu Leu Thr Ala Thr Leu915591609165acc ctc gcc gac aac aac aca caa cta ctc acc ggc cgc ctc tcc cta 27606Thr Leu Ala Asp Asn Asn Thr Gln Leu Leu Thr Gly Arg Leu Ser Leu917091759180cgc acc cac ccc tgg ctc acc gac cac acc gtc gcc ggc atg gtc ctc 27654Arg Thr His Pro Trp Leu Thr Asp His Thr Val Ala Gly Met Val Leu9185 919091959200ctg ccg ggc acc gcg ctc ctc gaa ctc gcc ctc caa gcc ggc gaa cgg 27702Leu Pro Gly Thr Ala Leu Leu Glu Leu Ala Leu Gln Ala Gly Glu Arg920592109215gtg gac tgc cct cgg gtg gag gaa ctg acc ctg cac gca ccg ttg gtg 27750Val Asp Cys Pro Arg Val Glu Glu Leu Thr Leu His Ala Pro Leu Val922092259230atc ccg cac acc gag gac gtg acg ttg cag gtc acc gtt cgg gca gcc 27798Ile Pro His Thr Glu Asp Val Thr Leu Gln Val Thr Val Arg Ala Ala923592409245gat gag agt ggc cat cgc gcc ctc gcg atc cac tcg tac tcc ggc acc 27846Asp Glu Ser Gly His Arg Ala Leu Ala Ile His Ser Tyr Ser Gly Thr925092559260gcg tcg tcg gcg gac cgg gag tgg acc cgt cac gcc acg ggc ctc ctc 27894Ala Ser Ser Ala Asp Arg Glu Trp Thr Arg His Ala Thr Gly Leu Leu9265 927092759280aca cac cac gcc gac acc gat cac cgt gcc gac acg cac acg gac gcg 27942Thr His His Ala Asp Thr Asp His Arg Ala Asp Thr His Thr Asp Ala928592909295tgc ctt ggc ggg agc tgg ccc ccg ccc ggc gcg cag ccc atc gaa ctg 27990Cys Leu Gly Gly Ser Trp Pro Pro Pro Gly Ala Gln Pro Ile Glu Leu930093059310ggc gac gtc tac ggt cgt atg gcg gcg gac tcg gac atc gcc tac ggg 28038Gly Asp Val Tyr Gly Arg Met Ala Ala Asp Ser Asp Ile Ala Tyr Gly931593209325ccg gtc ttc cag ggg ctg cac gcc gcc tgg agg ttc ggc gac gat gtc 28086Pro Val Phe Gln Gly Leu His Ala Ala Trp Arg Phe Gly Asp Asp Val933093359340ctg gcc gag gtg cgt ctg ccg gaa gag gct ctg cgc gat gct ccg gcg 28134Leu Ala Glu Val Arg Leu Pro Glu Glu Ala Leu Arg Asp Ala Pro Ala9245 935093559360gcg gcc ttc ggt gtt cac ccg gcc ttg ctc gac gcg gcc ctg cac gcc 28182Ala Ala Phe Gly Val His Pro Ala Leu Leu Asp Ala Ala Leu His Ala936593709375acg gcg ctc acc ccc cag aac ggg gac ggc tcg acg gag aac gtc gcc 28230Thr Ala Leu Thr Pro Gln Asn Gly Asp Gly Ser Thr Glu Asn Val Ala938093859390cag gag agc atg cct gac cgc gca gcc cac cag gcg cga ctg ccg ttc 28278Gln Glu Ser Met Pro Asp Arg Ala Ala His Gln Ala Arg Leu Pro Phe939594009405agc tgg agc ggc gtg tcc ctg cac acg gcg ggc agt tcc gtg ttg cgc 28326Ser Trp Ser Gly Val Ser Leu His Thr Ala Gly Ser Ser Val Leu Arg941094159420gta cgg ctg tcg cgc agt ccg cag cac ggt aat gcc gtg gcc ctc acc 28374Val Arg Leu Ser Arg Ser Pro Gln His Gly Asn Ala Val Ala Leu Thr9425 943094359440gcg gcc gac gag gac ggt cgg ccg gtg gtg acg atc gag tcg ctc gcg 28422Ala Ala Asp Glu Asp Gly Arg Pro Val Val Thr Ile Glu Ser Leu Ala944594509455ctg cgg ccg gtg tcc acc gag gag ctg cgc gcg gcc gcg gat cgt acg 28470Leu Arg Pro Val Ser Thr Glu Glu Leu Arg Ala Ala Ala Asp Arg Thr946094659470ccc gag cac gag tcg ctc ttc cga ctg gac tgg gtt tcc gta cca gtg 28518Pro Glu His Glu Ser Leu Phe Arg Leu Asp Trp Val Ser Val Pro Val947594809485ccc gcc aac gcc cct tcg ccc acc gcg gac cgg ccc tgg gcg gtc atc 28566Pro Ala Asn Ala Pro Ser Pro Thr Ala Asp Arg Pro Trp Ala Val Ile949094959500ggc gcg ggc ctt ccc cac ctg ccc ggc ctg acg gag cac gag cac gtg 28614Gly Ala Gly Leu Pro His Leu Pro Gly Leu Thr Glu His Glu His Val9505 951095159520acc gcg tat gac gag ccg gcg gac ctg ctt ctg gct ctg gac cgc ggt 28662Thr Ala Tyr Asp Glu Pro Ala Asp Leu Leu Leu Ala Leu Asp Arg Gly952595309535gct ccg ccg ccc ggt gtg ctg gtc gta ggt ggt gtc gcc cac acc gaa 28710Ala Pro Pro Pro Gly Val Leu Val Val Gly Gly Val Ala His Thr Glu95409545 9550gcc cgg gag tat tcc gcc gaa gcc ccc ggg gag cgc ggg acc gag gcc 28758Ala Arg Glu Tyr Ser Ala Glu Ala Pro Gly Glu Arg Gly Thr Glu Ala955595609565tgc gag gcc cgg ccg gac gtc gtg cac gtg ggc gtc gtg cac acg gct 28806Cys Glu Ala Arg Pro Asp Val Val His Val Gly Val Val His Thr Ala957095759580gcc gtg cac gcg gct gcc gcg cag atg ttg gcc agg ctc cag gcc tgg 28854Ala Val His Ala Ala Ala Ala Gln Met Leu Ala Arg Leu Gln Ala Trp9585 959095959600ctg ggc gac gag cgc ctc gca gac agc cgg ctg ctc gtc ctg acg tgc 28902Leu Gly Asp Glu Arg Leu Ala Asp Ser Arg Leu Leu Val Leu Thr Cys960596109615ggc gcg gtc gcc cgc gcc tcc ggc gac gat gcg acg gac ctg ccc ggg 28950Gly Ala Val Ala Arg Ala Ser Gly Asp Asp Ala Thr Asp Leu Pro Gly962096259630gcc gcc gtg tgg ggg ctg gtg cgt tcg gcg cag tcc gag cac ccg gac 28998Ala Ala Val Trp Gly Leu Val Arg Ser Ala Gln Ser Glu His Pro Asp963596409645cgc atc acg ctg ctg gac ttc gag cgg ggc aca gag gcg gag ccc ggt 29046Arg Ile Thr Leu Leu Asp Phe Glu Arg Gly Thr Glu Ala Glu Pro Gly965096559660cag ctg gcg acg gcg ctg aac tgc ggg gag cgg cag ctt gcc gtc cgc 29094Gln Leu Ala Thr Ala Leu Asn Cys Gly Glu Arg Gln Leu Ala Val Arg9665 967096759680ccc gga ggg ctg ttc acg cca cgg ctg gtg cgc gcg cca cgt gtc gcc 29142Pro Gly Gly Leu Phe Thr Pro Arg Leu Val Arg Ala Pro Arg Val Ala968596909695gac gcc gta ccc gcc gta ccc gcc gtg gcc gta ccg tca gcg ggt cac 29190Asp Ala Val Pro Ala Val Pro Ala Val Ala Val Pro Ser Ala Gly His970097059710gca gcc gta ccg gca gcg ggt ccc ttc ctt ccg ggc gga acg gtg ctg 29238Ala Ala Val Pro Ala Ala Gly Pro Phe Leu Pro Gly Gly Thr Val Leu971597209725atc acc ggc gga acc ggt gtc ctg ggc cgg ctc gtg gcc cgg cat ctg 29286Ile Thr Gly Gly Thr Gly Val Leu Gly Arg Leu Val Ala Arg His Leu973097359740gtg gag gcg cac ggc gta cgg cat ctg ttg ctg gcg ggt cgg cgc gga 29334Val Glu Ala His Gly Val Arg His Leu Leu Leu Ala Gly Arg Arg Gly9745 975097559760ccg gac gcc gag ggt gcg ccg gag ttg cgg gcg gag ctc ggt ggg ctc 29382Pro Asp Ala Glu Gly Ala Pro Glu Leu Arg Ala Glu Leu Gly Gly Leu976597709775ggc gcg acg gtg gag gtc gtc gcc tgc gac gcg gcg gac cgg cag cag 29430Gly Ala Thr Val Glu Val Val Ala Cys Asp Ala Ala Asp Arg Gln Gln978097859790ctg gcc gac ctg ctg aca cgg atc ccc gac gat cgg ccg ctg acc ggt 29478Leu Ala Asp Leu Leu Thr Arg Ile Pro Asp Asp Arg Pro Leu Thr Gly979598009805gtc gtg cac agt gcg ggc atc ctg gac gac ggc gtg atc acg tcg ctg 29526Val Val His Ser Ala Gly Ile Leu Asp Asp Gly Val Ile Thr Ser Leu981098159820tcg ccg gag cgg ctc ggg gcc gtc ctc cgg gcc aag gcg gac gct gcg 29574Ser Pro Glu Arg Leu Gly Ala Val Leu Arg Ala Lys Ala Asp Ala Ala9825 983098359840ctg ctt ctc gac gag ctg acg cgc ggg gca gag ctg tcg gct ttc gtc 29622Leu Leu Leu Asp Glu Leu Thr Arg Gly Ala Glu Leu Ser Ala Phe Val984598509855atg ttc tcc tcc gcg tcg gcg gtg gtc ggc tcg ccc ggg cag ggc aac 29670Met Phe Ser Ser Ala Ser Ala Val Val Gly Ser Pro Gly Gln Gly Asn986098659870tac gcc gcc gcc aac gcc gtc ctc gac ttc ctt gct cat cgc cgc cgc 29718Tyr Ala Ala Ala Asn Ala Val Leu Asp Phe Leu Ala His Arg Arg Arg987598809885gcc gag ggg ctg ccc gcc gtc tct ctc gcc tgg ggc ctg tgg gaa gag 29766Ala Glu Gly Leu Pro Ala Val Ser Leu Ala Trp Gly Leu Trp Glu Glu989098959900ggc aca ggg atg acg ggc cac ctc gac gtc gac gac cat gcg cgg atc 29814Gly Thr Gly Met Thr Gly His Leu Asp Val Asp Asp His Ala Arg Ile9905 991099159920agc cgc gcg gga atg cgg ccg ctg ccg act gcc gag gct ctg gcg ctg 29862Ser Arg Ala Gly Met Arg Pro Leu Pro Thr Ala Glu Ala Leu Ala Leu992599309935ttc gac gcg gcc ttg gcc gac ggc gag ccg ttc ctg atg ccg gct cgg 29910Phe Asp Ala Ala Leu Ala Asp Gly Glu Pro Phe Leu Met Pro Ala Arg994099459950ctc gac ctc acg gcc gta cgg tct ggt gcc gcg tcc gca ccg gtg ccg 29958Leu Asp Leu Thr Ala Val Arg Ser Gly Ala Ala Ser Ala Pro Val Pro995599609965ccg ctg ctg caa ggt ctg ctt cag ctg cct cgg tcc cgc tcg gcc gcc 30006Pro Leu Leu Gln Gly Leu Leu Gln Leu Pro Arg Ser Arg Ser Ala Ala997099759980gcg gcc ccc ggc cat ggg gcc ccg gcg gcg gac gag gcg gcg gcc tgg 30054Ala Ala Pro Gly His Gly Ala Pro Ala Ala Asp Glu Ala Ala Ala Trp9985 99909995 10000cgt gag cgt ctg gcc cgg cag agt gcc ggt gag cgc agg cag gcg ctg 30102Arg Glu Arg Leu Ala Arg Gln Ser Ala Gly Glu Arg Arg Gln Ala Leu10005 10010 10015ctg cgc ctg gtg cgg tcg cat gtc gcg gcg gtg ctc ggc cat agc ggt 30150Leu Arg Leu Val Arg Ser His Val Ala Ala Val Leu Gly His Ser Gly10020 10025 10030gcc gac gga atc gac gca tcg cgg gcg ttc cgc gag ctg ggg ttc gac 30198Ala Asp Gly Ile Asp Ala Ser Arg Ala Phe Arg Glu Leu Gly Phe Asp10035 10040 10045tcg ctc acg gcg gtc gag ctg cgc aac cgt ctc acg gcc gcg acg ggc 30246Ser Leu Thr Ala Val Glu Leu Arg Asn Arg Leu Thr Ala Ala Thr Gly10050 10055 10060ctg cgg ctg cgg gcc acg ctg gcc ttc gat ttc ccg acc ccg gca gcg 30294Leu Arg Leu Arg Ala Thr Leu Ala Phe Asp Phe Pro Thr Pro Ala Ala10065 10070 10075 10080ctg gcc gag cac ttg ggc gag cgt ctg ctt ccc gac cag gag gcc acg 30342Leu Ala Glu His Leu Gly Glu Arg Leu Leu Pro Asp Gln Glu Ala Thr10085 10090 10095ggc gag caa gcc ggc gat cag ctc tcc ggc ggc agc gag gag gac gta 30390Gly Glu Gln Ala Gly Asp Gln Leu Ser Gly Gly Ser Glu Glu Asp Val10100 10105 10110cgc agc ctc ctg acg tcc att ccg atc ggc agg ctg cgg gac gcg ggg 30438Arg Ser Leu Leu Thr Ser Ile Pro Ile Gly Arg Leu Arg Asp Ala Gly10115 10120 10125ctc ctc ggg ccc ctg ctc acg ctc gcg gac acg ggc cgc ggc gcc tcg 30486Leu Leu Gly Pro Leu Leu Thr Leu Ala Asp Thr Gly Arg Gly Ala Ser10130 10135 10140ggc gcc gcc gca ggt ccg gag gac gcg ccg ccc tcc ggc cag gac aca 30534Gly Ala Ala Ala Gly Pro Glu Asp Ala Pro Pro Ser Gly Gln Asp Thr10145 10150 10155 10160ccg gct ccc gtc tcg atc gac gag atg gac atc gac gac ctg atg gat 30582Pro Ala Pro Val Ser Ile Asp Glu Met Asp Ile Asp Asp Leu Met Asp10165 10170 10175ctg gcg cac ggg cat ggc acc gca ccc gcc cgt gag ccc gcc gac gca 30630Leu Ala His Gly His Gly Thr Ala Pro Ala Arg Glu Pro Ala Asp Ala10180 10185 10190gag gac tcg tcg tca tca cga aac cgg aca cac cac aca cac gaa ggt 30678Glu Asp Ser Ser Ser Ser Arg Asn Arg Thr His His Thr His Glu Gly10195 10200 10205gag aca gcg tga 30690Glu Thr Ala10210<210>2<211>31422<212>DNA<213>除蟲鏈霉菌<220><221>CDS<222>(1)..(14643)<220><221>CDS<222>(14824)..(31419)<400>2atg gct aac gag gaa aag ctc cgc gac tat ctc aag cgc gtt act gcc 48Met Ala Asn Glu Glu Lys Leu Arg Asp Tyr Leu Lys Arg Val Thr Ala1 5 10 15gat ctc ctc aat gtg cgg cgt cga ctt cag cag att gaa tcg ggc gag 96Asp Leu Leu Asn Val Arg Arg Arg Leu Gln Gln Ile Glu Ser Gly Glu20 25 30cag gag ccg att gca att gtg ggg atg gcg tgc cgt ttt ccg ggg ggt 144Gln Glu Pro Ile Ala Ile Val Gly Met Ala Cys Arg Phe Pro Gly Gly35 40 45gtg gag tcg gcg gag gat ttc tgg gag ttg att gcg tcg ggt cgg gat 192Val Glu Ser Ala Glu Asp Phe Trp Glu Leu Ile Ala Ser Gly Arg Asp50 55 60gcg gtg ggg gag ttt ccg gtc gac cgg ggt tgg gac gtg gag gct ttc 240Ala Val Gly Glu Phe Pro Val Asp Arg Gly Trp Asp Val Glu Ala Phe65 70 75 80tat gat ccg gag ccg ggg cgg gcg ggt tcg tcg tat acg cgc cgg ggc 288Tyr Asp Pro Glu Pro Gly Arg Ala Gly Ser Ser Tyr Thr Arg Arg Gly85 90 95ggt ttc ctg gag ggt gcg gcg gag ttc gat gcg ggg ttt ttc ggg atc 336Gly Phe Leu Glu Gly Ala Ala Glu Phe Asp Ala Gly Phe Phe Gly Ile100 105 110agt ccg cgt gag gcg ttg gcg atg gat ccg cag cag cgg ttg atg ctg 384Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Met Leu115 120 125gag gtg tcc tgg gag gcg ttg gag cgg gcg ggc atc gac ccc gcc acg 432Glu Val Ser Trp Glu Ala Leu Glu Arg Ala Gly Ile Asp Pro Ala Thr130 135 140ttg cgc ggc agc cgg acg ggc gtc ttc gcc ggc ctc atg tcc cag gac 480Leu Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Leu Met Ser Gln Asp145 150 155 160tac gcg acc cgt ctg ctc tcg gtc ccc gac gac ctg gcc ggc tac ctg 528Tyr Ala Thr Arg Leu Leu Ser Val Pro Asp Asp Leu Ala Gly Tyr Leu165 170 175ggc aac ggc aac gcg gga agc atc ctg tcc gga cgc gtc gcc tac acc 576Gly Asn Gly Asn Ala Gly Ser Ile Leu Ser Gly Arg Val Ala Tyr Thr180 185 190ttc ggc ttc gag ggc ccc gcg gtg acg gtc gac acg gcg tgc tcg tcg 624Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser195 200 205tcg ctg gtg gca ctg cac ctc gcc tgc cag tca ctg cgc acc ggt gag 672Ser Leu Val Ala Leu His Leu Ala Cys Gln Ser Leu Arg Thr Gly Glu210 215 220tcc tcc ttc gcc ctc gcc gga ggc gtg acg gtc atg tcc acc ccg ggc 720Ser Ser Phe Ala Leu Ala Gly Gly Val Thr Val Met Ser Thr Pro Gly225 230 235 240atg ttc gtg gag ttc tcg cgg cag cgg ggt ctg tcg ccg gac ggc cgg 768Met Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ser Pro Asp Gly Arg245 250 255tgc aag gcg tac gcg tcg gct gcc gac ggc acc ggc atg tcc gag ggc 816Cys Lys Ala Tyr Ala Ser Ala Ala Asp Gly Thr Gly Met Ser Glu Gly260 265 270gtg ggg att ttg ctg ctg gag cgg ctg tcc gag gct gaa cgt cgt ggt 864Val Gly Ile Leu Leu Leu Glu Arg Leu Ser Glu Ala Glu Arg Arg Gly275 280 285cat cgg gtt ttg gcg gtg gtg cgg ggg agt gcg gtg aat cag gac ggt 912His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly290 295 300gcg tcg aat ggg ttg acg gcg ccg aat ggt ccg tcg cag cag cgg gtg 960Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val305 310 315 320att cgg cag gcg ttg gcg tgt gcg ggg ttg tct gtg gcg gat gtg gat 1008Ile Arg Gln Ala Leu Ala Cys Ala Gly Leu Ser Val Ala Asp Val Asp325 330 335gtg gtg gag ggg cac ggg acg ggc acg acg ctg ggt gat ccg atc gag 1056Val Val Glu Gly His Gly Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu340 345 350gcg cag gcg ttg ctc gcc acg tac ggg cag cgg gcc ggt gac acg ccg 1104Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Arg Ala Gly Asp Thr Pro355 360 365gtg tgg ttg ggg tcg gtg aag tcg aac atc ggg cat gcg cag gct gct 1152Val Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Ala Gln Ala Ala370 375 380gcg ggt gtg gcg ggt gtg atc aag atg gtg atg gcg ttg cgg gcg ggg 1200Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ala Leu Arg Ala Gly385 390 395 400gtg ttg ccg cgg acg ttg cat gtg gat gag ccg tcg tcg cag gtg gat 1248Val Leu Pro Arg Thr Leu His Val Asp Glu Pro Ser Ser Gln Val Asp405 410 415tgg tcg agt ggg tcg gtt cgt gtg ttg gcg gat gag gtg gag tgg ccg 1296Trp Ser Ser Gly Ser Val Arg Val Leu Ala Asp Glu Val Glu Trp Pro420 425 430ggg gtg gag ggt cgg ctg cgg cgt gcg ggg gtg tct gcg ttc ggg gtg 1344Gly Val Glu Gly Arg Leu Arg Arg Ala Gly Val Ser Ala Phe Gly Val435 440 445agt ggg acg aat gcg cat gtg att ttg gag gag gcg tcg ggg ggc gcg 1392Ser Gly Thr Asn Ala His Val Ile Leu Glu Glu Ala Ser Gly Gly Ala450 455 460ggt ggg ggt gcg ggc cgg ctg cag gag ttg ggt ccg ggg gtg gtg tcg 1440Gly Gly Gly Ala Gly Arg Leu Gln Glu Leu Gly Pro Gly Val Val Ser465 470 475 480ggt tcg ggg gtg gtg ccg tgg gtg gtg tcg gcg cgg tcg gag ttg gcg 1488Gly Ser Gly Val Val Pro Trp Val Val Ser Ala Arg Ser Glu Leu Ala485 490 495ttg cgg ggg cag gcg cgt cgg ttg cgt ggg gtt gtg gcg gtt ggt ggg 1536Leu Arg Gly Gln Ala Arg Arg Leu Arg Gly Val Val Ala Val Gly Gly500 505 510ggt gcg gat ggt gtg ggg gtg agt ccg gct ggg gtc ggg cgg gct ttg 1584Gly Ala Asp Gly Val Gly Val Ser Pro Ala Gly Val Gly Arg Ala Leu515 520 525gtg tcg gag cgg tcg gtg ttc gag cat cgt gcg gtg gtc gtg gcc gag 1632Val Ser Glu Arg Ser Val Phe Glu His Arg Ala Val Val Val Ala Glu530 535 540gac cgc gac gag ttc ctg cac gca ctc gac gca ctg gcc ggc ggc cgc 1680Asp Arg Asp Glu Phe Leu His Ala Leu Asp Ala Leu Ala Gly Gly Arg545 550 555 560ccc gtg ccc ggc gtc gtc gag gga cga acc acc tcg ggc gaa ctc gcc 1728Pro Val Pro Gly Val Val Glu Gly Arg Thr Thr Ser Gly Glu Leu Ala565 570 575gta ctc ttc gcc ggg cag gga acc cag cgc gca ggc atg ggc cgc gaa 1776Val Leu Phe Ala Gly Gln Gly Thr Gln Arg Ala Gly Met Gly Arg Glu580 585 590ctg tac gag gcg tac ccc gtc ttc gcc cag gcc atc gac gag atc tgc 1824Leu Tyr Glu Ala Tyr Pro Val Phe Ala Gln Ala Ile Asp Glu Ile Cys595 600 605gcg gag gcc gac acc gcc cgc acc gac ccc ggt gcc cct ggg ctg cgg 1872Ala Glu Ala Asp Thr Ala Arg Thr Asp Pro Gly Ala Pro Gly Leu Arg610 615 620gac gta ctc ttc gca ccg cag gac tct ccc gaa ggc cgg ctg atc gag 1920Asp Val Leu Phe Ala Pro Gln Asp Ser Pro Glu Gly Arg Leu Ile Glu625 630 635 640gac acg ggt ttc gcc cag ccc gcc ctg ttc gcc ttc gag gtg gcg ctg 1968Asp Thr Gly Phe Ala Gln Pro Ala Leu Phe Ala Phe Glu Val Ala Leu645 650 655ttc cgg ctg ctg gag acc tgg ggt ctg acg ccc gac tac gtc ctc ggc 2016Phe Arg Leu Leu Glu Thr Trp Gly Leu Thr Pro Asp Tyr Val Leu Gly660 665 670cat tcc gtc ggt gaa ctg gcg gcc gcc cat gtc gcc ggg atg ctc tgc 2064His Ser Val Gly Glu Leu Ala Ala Ala His Val Ala Gly Met Leu Cys675 680 685ctt gcc gac gcg gtg gca ctg gtg gtc gca cga ggc cgc ctg atg caa 2112Leu Ala Asp Ala Val Ala Leu Val Val Ala Arg Gly Arg Leu Met Gln690 695 700ggg ctc ccg tcc ggc gga gcc atg gtg gcc atc gag gcg tcc gag gac 2160Gly Leu Pro Ser Gly Gly Ala Met Val Ala Ile Glu Ala Ser Glu Asp705 710 715 720gag atc ctc ccg ctg ccc gac gaa tac gca tcc cgg gtc gcg cac gcc 2208Glu Ile Leu Pro Leu Pro Asp Glu Tyr Ala Ser Arg Val Ala His Ala725 730 735gcg gtg aac ggg ccg cgg tcg atc gtc ctc tcc ggg gac gag gac gcg 2256Ala Val Asn Gly Pro Arg Ser Ile Val Leu Ser Gly Asp Glu Asp Ala740 745 750gtc ctg gac ctc gcg cag caa tgg gcg gca cga ggc cgc cgc acc cgg 2304Val Leu Asp Leu Ala Gln Gln Trp Ala Ala Arg Gly Arg Arg Thr Arg755 760 765cgg ctg cgg acc agc cac gcc ttc cac tcg ccg cac atg gac gcc atg 2352Arg Leu Arg Thr Ser His Ala Phe His Ser Pro His Met Asp Ala Met770 775 780ttg ggc gac ttc cgc cgc gcg gcc gag cag gtc acc ttc agc gcc ccg 2400Leu Gly Asp Phe Arg Arg Ala Ala Glu Gln Val Thr Phe Ser Ala Pro785 790 795 800cgg att ccc gtc gtc tcc aac gtc acc ggc gcg ccc ctc ccc gcc gag 2448Arg Ile Pro Val Val Ser Asn Val Thr Gly Ala Pro Leu Pro Ala Glu805 810 815acc atg tgc acc ccg gac tac tgg gtc gaa cac gcc cgc agc acg gtc 2496Thr Met Cys Thr Pro Asp Tyr Trp Val Glu His Ala Arg Ser Thr Val820 825 830cgt ttc gcg gac ggc atc tca tgg ctt cag gaa cag ggc gtc acc acc 2544Arg Phe Ala Asp Gly Ile Ser Trp Leu Gln Glu Gln Gly Val Thr Thr835 840 845tgc ctc gaa atc ggc ccc gac ggc acg ctg tcg gcc ctc gca cag gac 2592Cys Leu Glu Ile Gly Pro Asp Gly Thr Leu Ser Ala Leu Ala Gln Asp850 855 860tcg ctc agt gca ccg gcc cgc gcc atc ccc gcc ctg cgg ccg gac cag 2640Ser Leu Ser Ala Pro Ala Arg Ala Ile Pro Ala Leu Arg Pro Asp Gln865 870 875 880ccg gag gca cgg tcg gtc atg acc gcc ctg gcg gag ttg ttc gtg gct 2688Pro Glu Ala Arg Ser Val Met Thr Ala Leu Ala Glu Leu Phe Val Ala885 890 895ggg acg gcg gtt gag tgg gcc ggt gtg ttc gag ggg act gct cgc gag 2736Gly Thr Ala Val Glu Trp Ala Gly Val Phe Glu Gly Thr Ala Arg Glu900 905 910gtc ggt gat gga tgc ggg gtg gag ctg ccg acg tat gcg ttt gag cgg 2784Val Gly Asp Gly Cys Gly Val Glu Leu Pro Thr Tyr Ala Phe Glu Arg915 920 925gag cga ttt tgg ctg gac gtg gag gag gga tct gcg gga ggt tcc ggg 2832Glu Arg Phe Trp Leu Asp Val Glu Glu Gly Ser Ala Gly Gly Ser Gly930 935 940gtt tcc ggg atg tgg ggt ggt ccg ttg tgg gag gcg gtc gag tgt ggt 2880Val Ser Gly Met Trp Gly Gly Pro Leu Trp Glu Ala Val Glu Cys Gly945 950 955 960gat gcg ggg gtg gtg gca tcg ctc ctt ggg gtg gat gag ggg gcg tcg 2928Asp Ala Gly Val Val Ala Ser Leu Leu Gly Val Asp Glu Gly Ala Ser965 970 975ctg ggt gcg gtg gtg tcg gcg ttg ggg gaa tgg ggg cgg gta cgg cac 2976Leu Gly Ala Val Val Ser Ala Leu Gly Glu Trp Gly Arg Val Arg His980 985 990gag cgt gaa gtg gtg gac ggg tgg cgc tat cgg gag gtg tgg cga ccc 3024Glu Arg Glu Val Val Asp Gly Trp Arg Tyr Arg Glu Val Trp Arg Pro99510001005gtt tcg ggc ggt ggt gta ggg ggg ctg tcg ggc gcg tgg ctg gtg gtg 3072Val Ser Gly Gly Gly Val Gly Gly Leu Ser Gly Ala Trp Leu Val Val101010151020tcc gag ggc gag gcg ggc ccg gtt gat gtg gtg gcg gag ggg ttg gag 3120Ser Glu Gly Glu Ala Gly Pro Val Asp Val Val Ala Glu Gly Leu Glu1025 103010351040cgg tgt ggg gcg cga gtg gtt cgg gtg gag gtg gaa gcg ggg tgt gtg 3168Arg Cys Gly Ala Arg Val Val Arg Val Glu Val Glu Ala Gly Cys Val104510501055agc agg gaa gtg ttg gcc ggc cac ctg cgt gag gcg gtc gat ggt gag 3216Ser Arg Glu Val Leu Ala Gly His Leu Arg Glu Ala Val Asp Gly Glu106010651070gct gtc ggc ggt gtc gtc tcc ctt gtg ggc tgg ggg agt ggc gtc gtg 3264Ala Val Gly Gly Val Val Ser Leu Val Gly Trp Gly Ser Gly Val Val107510801085cag gcg gga gtg gcg tct gtg ggg ttg gtg cag gcg ctg ggt gat gtg 3312Gln Ala Gly Val Ala Ser Val Gly Leu Val Gln Ala Leu Gly Asp Val109010951100ggc gtg ggg gcg cgg ctg tgg tgt gtg acg ggc ggg gcc gtg tcg gtg 3360Gly Val Gly Ala Arg Leu Trp Cys Val Thr Gly Gly Ala Val Ser Val1105 111011151120ggg ggc cgg gat gct gtg tgg ggg ccg gcc tcg ggt gtg gtg tgg ggg 3408Gly Gly Arg Asp Ala Val Trp Gly Pro Ala Ser Gly Val Val Trp Gly112511301135ctg ggc cgt gtg gtg ggg gcg gag gca ccg gac cgc tgg ggt ggg ctg 3456Leu Gly Arg Val Val Gly Ala Glu Ala Pro Asp Arg Trp Gly Gly Leu114011451150gtt gat gtg ccg gag ctc gtg gat gag cgg gtg gtc gat ggg ttg gta 3504Val Asp Val Pro Glu Leu Val Asp Glu Arg Val Val Asp Gly Leu Val115511601165ggt gtg ctg gcg ggt gtg ggg gga ggg ggt gag agt gag ttt gcc gtg 3552Gly Val Leu Ala Gly Val Gly Gly Gly Gly Glu Ser Glu Phe Ala Val117011751180cgg tct tcg ggg gcg ttt gtg cgg cgg ttg gtg cgg gcg ccg ttg gag 3600Arg Ser Ser Gly Ala Phe Val Arg Arg Leu Val Arg Ala Pro Leu Glu1185 119011951200gag gcc gtc gcg gag cgg gag tgg cgg ccc cgc ggc acc gta ctc gtc 3648Glu Ala Val Ala Glu Arg Glu Trp Arg Pro Arg Gly Thr Val Leu Val120512101215acc gga ggc acc ggc gag ttg ggt gcg cac gtc gcc cgg tgg atg gcc 3696Thr Gly Gly Thr Gly Glu Leu Gly Ala His Val Ala Arg Trp Met Ala122012251230cgg cgt ggc gcc gaa cac ctg ctg ctg gtg agc cga cgc ggg gag agc 3744Arg Arg Gly Ala Glu His Leu Leu Leu Val Ser Arg Arg Gly Glu Ser123512401245gcc cag gga gtc gaa gaa ctc cga gcg gac ttg atg ggc ttg ggc gcg 3792Ala Gln Gly Val Glu Glu Leu Arg Ala Asp Leu Met Gly Leu Gly Ala125012551260cgg gtg tcg gtg gtg gcg tgt gat gcg gcg gac cgt gag gcg ttg gcg 3840Arg Val Ser Val Val Ala Cys Asp Ala Ala Asp Arg Glu Ala Leu Ala1265 127012751280gag gtg ttg cgg tcg gcc gtt ccg gcg gag tgc ccg ctg ggt gtg gtg 3888Glu Val Leu Arg Ser Ala Val Pro Ala Glu Cys Pro Leu Gly Val Val128512901295gtg cat gcc gcg gga gtt gtg gat gac ggg gtg ttg gag ggg ttg tcg 3936Val His Ala Ala Gly Val Val Asp Asp Gly Val Leu Glu Gly Leu Ser130013051310tcc gag cgt gtc acg ggg gtg ctg cgg gcg aag gcg ctg gcg gcc tgg 3984Ser Glu Arg Val Thr Gly Val Leu Arg Ala Lys Ala Leu Ala Ala Trp131513201325aat ctg cat gag ttg acg cgg ggg gcg gat ctt tcg ggg ttc gtg gtg 4032Asn Leu His Glu Leu Thr Arg Gly Ala Asp Leu Ser Gly Phe Val Val133013351340ttc tcg tcg gct gcg gcg acg ttc ggg ccg gcg gga cag ggg agt tac 4080Phe Ser Ser Ala Ala Ala Thr Phe Gly Pro Ala Gly Gln Gly Ser Tyr1345 135013551360gcg gcg gcg aac gcg tat gtg gag gca atc gtt cgg cac cgg cgt ggt 4128Ala Ala Ala Asn Ala Tyr Val Glu Ala Ile Val Arg His Arg Arg Gly136513701375gag ggc ctg ccg ggg ttg gcg gtg gcg tgg ggt ccg tgg gct ggt ggg 4176Glu Gly Leu Pro Gly Leu Ala Val Ala Trp Gly Pro Trp Ala Gly Gly138013851390ggg atg gcg gag ggg gcc gtg ggg cag atg cgg cgt cgg ggt ctg gcg 4224Gly Met Ala Glu Gly Ala Val Gly Gln Met Arg Arg Arg Gly Leu Ala139514001405gcg atg acg ccg gag acg gcg ctg gtg gca ctg ggc cag gcg ttg gac 4272Ala Met Thr Pro Glu Thr Ala Leu Val Ala Leu Gly Gln Ala Leu Asp141014151420cat gac gag acc tgt gtg acg gtc gcc gac atc gac tgg gac cga ttc 4320His Asp Glu Thr Cys Val Thr Val Ala Asp Ile Asp Trp Asp Arg Phe1425 143014351440acc gcc aac tcc ctc ccc ggc tcc cga ctc tcg ccc ctc atc agc gac 4368Thr Ala Asn Ser Leu Pro Gly Ser Arg Leu Ser Pro Leu Ile Ser Asp144514501455atc ccc gaa gca cgc ctc gcc cgg gaa acc acc gga ctc gac acc gcc 4416Ile Pro Glu Ala Arg Leu Ala Arg Glu Thr Thr Gly Leu Asp Thr Ala146014651470acc gca tcc ccc gac tcg ttc tcc gca cgg ctc aag gcc atg gac acc 4464Thr Ala Ser Pro Asp Ser Phe Ser Ala Arg Leu Lys Ala Met Asp Thr147514801485gcc gag cag gaa cgt gcg ctt ctc gac ctg gtc cgt acg tac gcg gcg 4512Ala Glu Gln Glu Arg Ala Leu Leu Asp Leu Val Arg Thr Tyr Ala Ala149014951500acc gtg ctc gga cac agc acc ccc acc gcc gta cgc cct gag cga gcc 4560Thr Val Leu Gly His Ser Thr Pro Thr Ala Val Arg Pro Glu Arg Ala1505 151015151520ttc cgc gac ctg ggc ttc gtc tcc gtg agc gcc gtc gaa ctg cgc aac 4608Phe Arg Asp Leu Gly Phe Val Ser Val Ser Ala Val Glu Leu Arg Asn152515301535cgc ctc aac gcc gtc acc ggg ctc ctc ctg ccc acc acg ctg atc ttc 4656Arg Leu Asn Ala Val Thr Gly Leu Leu Leu Pro Thr Thr Leu Ile Phe154015451550gac tac ccc act ccc tcc gcg ctg gcc gga tac ctc aag gaa cag ctg 4704Asp Tyr Pro Thr Pro Ser Ala Leu Ala Gly Tyr Leu Lys Glu Gln Leu155515601565gag gag ggc gcg ggc ggc cag cgt gac att gct cct ccg gtc ccg gcg 4752Glu Glu Gly Ala Gly Gly Gln Arg Asp Ile Ala Pro Pro Val Pro Ala157015751580tcg cgt gtc gac gtt gac gag ccg att gcg att gtg ggg atg gcg tgc 4800Ser Arg Val Asp Val Asp Glu Pro Ile Ala Ile Val Gly Met Ala Cys1585 159015951600cgt ttt ccg ggg ggt gtg gag tcg gcg gag gac ttg tgg gaa ctg gtc 4848Arg Phe Pro Gly Gly Val Glu Ser Ala Glu Asp Leu Trp Glu Leu Val160516101615gcg tcg ggt cgg gat gcg gtg gga gag ttt ccg gtc gac cgg ggt tgg 4896Ala Ser Gly Arg Asp Ala Val Gly Glu Phe Pro Val Asp Arg Gly Trp162016251630gac gtg gag gct ttc tat gat ccg gag ccg ggg cgg gcg ggt tcg tcg 4944Asp Val Glu Ala Phe Tyr Asp Pro Glu Pro Gly Arg Ala Gly Ser Ser163516401645tat acg cgc cgg ggc ggt ttc ctg gag ggt gcg gcg gag ttc gat gcg 4992Tyr Thr Arg Arg Gly Gly Phe Leu Glu Gly Ala Ala Glu Phe Asp Ala165016551660ggg ttt ttc ggg atc agt ccg cgt gag gcg ttg gcg atg gat ccg cag 5040Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln1665 167016751680cag cgg ttg atg ctg gag gtg tcc tgg gag gcg ttg gag cgg gcg ggc 5088Gln Arg Leu Met Leu Glu Val Ser Trp Glu Ala Leu Glu Arg Ala Gly168516901695atc gac ccc gcc acg ttg cgc ggg tcc acg acc ggt gtc ttc gcc ggc 5136Ile Asp Pro Ala Thr Leu Arg Gly Ser Thr Thr Gly Val Phe Ala Gly170017051710atg tgc agt cag gac tac gcc gac ctc gtg cgc cgg gcc acc gag gac 5184Met Cys Ser Gln Asp Tyr Ala Asp Leu Val Arg Arg Ala Thr Glu Asp171517201725ctc gag ggc tac gcc atg acg ggc ctg tcc agc agc gtc aca tcc gga 5232Leu Glu Gly Tyr Ala Met Thr Gly Leu Ser Ser Ser Val Thr Ser Gly173017351740cgc gtc gcc tac acc ctg ggg ctc gag ggt ccg gcg gtg acg gtg gat 5280Arg Val Ala Tyr Thr Leu Gly Leu Glu Gly Pro Ala Val Thr Val Asp1745 175017551760acg gcg tgt tcg tcg tcg ttg gtg gcg ctg cat ctg gcg tgt cag gcg 5328Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys Gln Ala176517701775ttg agg tcg ggg gag tgt tcg ctg gcg ttg gcg ggg ggt gtg acg gtg 5376Leu Arg Ser Gly Glu Cys Ser Leu Ala Leu Ala Gly Gly Val Thr Val178017851790atg tcg acg ccg ggt gcg ttt gtg gag ttc tcg cgg cag cgg ggt ctg 5424Met Ser Thr Pro Gly Ala Phe Val Glu Phe Ser Arg Gln Arg Gly Leu179518001805tcg ccg gac ggc cgg tgc aag gcg tac ggg tcg ggg gcc gat ggg gtc 5472Ser Pro Asp Gly Arg Cys Lys Ala Tyr Gly Ser Gly Ala Asp Gly Val181018151820ggc tgg gcc gag ggt gtg ggt gtg ctg ttg gtg gag cgg ctg tcc gag 5520Gly Trp Ala Glu Gly Val Gly Val Leu Leu Val Glu Arg Leu Ser Glu1825 183018351840gct gaa cgt cgt ggt cat cgg gtt ttg gcg gtg gtg cgg ggg agt gcg 5568Ala Glu Arg Arg Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala184518501855gtg aat cag gac ggt gcg tcg aat ggg ttg acg gcg ccg aat ggt ccg 5616Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro186018651870tcg cag cag cgg gtg att cgg cag gcg ttg gcg tgt gcg ggg ttg tcc 5664Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Cys Ala Gly Leu Ser187518801885gtg gcg gat gtg gat gtg gtg gag ggg cac ggg acg ggt acg acg ttg 5712Val Ala Asp Val Asp Val Val Glu Gly His Gly Thr Gly Thr Thr Leu189018951900ggt gat ccg atc gag gcg cag gcg ttg ctc gcc act tat ggg cag ggt 5760Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Gly1905 191019151920cgt tcg ggg gag cgg ccg gtg tgg ttg ggg tcg gtg aag tcg aac arc 5808Arg Ser Gly Glu Arg Pro Val Trp Leu Gly Ser Val Lys Ser Asn Ile192519301935ggg cat gcg cag gct gct gcg ggt gtg gcg ggt gtg atc aag atg gtg 5856Gly His Ala Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val194019451950atg gcg ttg cgg gcg ggg gtg ttg ccg cgg acg ttg cat gtg gat gag 5904Met Ala Leu Arg Ala Gly Val Leu Pro Arg Thr Leu His Val Asp Glu195519601965ccg tcg tcg cag gtg gat tgg tcg agt ggg tcg gtt cgt gtg ttg gcg 5952Pro Ser Ser Gln Val Asp Trp Ser Ser Gly Ser Val Arg Val Leu Ala197019751980gat gag gtg gag tgg ccg ggg gtg gag ggt cgg ctg cgg cgt gcg ggg 6000Asp Glu Val Glu Trp Pro Gly Val Glu Gly Arg Leu Arg Arg Ala Gly1985 199019952000gtg tct gcg ttc ggg gtg agt ggg acg aat gcg cat gtg att ttg gag 6048Val Ser Ala Phe Gly Val Ser Gly Thr Asn Ala His Val Ile Leu Glu200520102015gag gcg tcc ggg ggc gcg gat ggg ggt gcg ggc cgg ctg cag gag ttg 6096Glu Ala Ser Gly Gly Ala Asp Gly Gly Ala Gly Arg Leu Gln Glu Leu202020252030ggt ccg ggg gtg gtg tcg ggt tcg ggg gtg gtg ccg tgg gtg gtg tcg 6144Gly Pro Gly Val Val Ser Gly Ser Gly Val Val Pro Trp Val Val Ser203520402045gcg cgg tcg gag ttg gcg ttg cgg ggg cag gcg cgt cgg ttg cgt ggg 6192Ala Arg Ser Glu Leu Ala Leu Arg Gly Gln Ala Arg Arg Leu Arg Gly2050 2055 2060gtt gtg gcg gtt ggt ggg ggt gcg gat ggt gtg ggg gtg agt ccg gct 6240Val Val Ala Val Gly Gly Gly Ala Asp Gly Val Gly Val Ser Pro Ala2065 2070 2075 2080ggg gtc ggg cgg gct ttg gtg tcg gag cgg tcg gtg ttc gag cat cgt 6288Gly Val Gly Arg Ala Leu Val Ser Glu Arg Ser Val Phe Glu His Arg208520902095gcg gtg gtc gtg gcc gag gac cgc gac gag ttc ctg cac gca ctc gac 6336Ala Val Val Val Ala Glu Asp Arg Asp Glu Phe Leu His Ala Leu Asp210021052110gca ctg gcc gag ggg gca ccc acc gcg ggg gtg gta cag ggt gtg gcc 6384Ala Leu Ala Glu Gly Ala Pro Thr Ala Gly Val Val Gln Gly Val Ala211521202125gga ccg gcg gcc gac gga aag atc gcc atg ctg ttc gga gga cag ggc 6432Gly Pro Ala Ala Asp Gly Lys Ile Ala Met Leu Phe Gly Gly Gln Gly213021352140acc cac tgg gaa ggc atg gcg cag gaa ctc ctc ggc tcc tca ccg gtc 6480Thr His Trp Glu Gly Met Ala Gln Glu Leu Leu Gly Ser Ser Pro Val2145 215021552160ttc gcc cag cag atg tcc gac tgc gcc caa gcc ctc gaa ccg tac ctg 6528Phe Ala Gln Gln Met Ser Asp Cys Ala Gln Ala Leu Glu Pro Tyr Leu216521702175gac tgg tct ctc ctc gac gtc ctg cgc ggc gca ccg gac gca ccc cct 6576Asp Trp Ser Leu Leu Asp Val Leu Arg Gly Ala Pro Asp Ala Pro Pro218021852190ctg caa cgc gtc gat gtc gtc cag ccc gtc ctc ttc gcg gtg atg gtc 6624Leu Gln Arg Val Asp Val Val Gln Pro Val Leu Phe Ala Val Met Val219522002205tcg ctg gcg gcg ctc tgg cgc tcg tac ggt gta cac ccg gac gcg gtg 6672Ser Leu Ala Ala Leu Trp Arg Ser Tyr Gly Val His Pro Asp Ala Val221022152220gcc ggg cac tcg cag ggc gag atc gca gcg gcc tac gtc gcc ggt gca 6720Ala Gly His Ser Gln Gly Glu Ile Ala Ala Ala Tyr Val Ala Gly Ala2225 223022352240ctc tcc ctc gac gac gcc gcc cgg gtc acc gcc ctg cgc agc cag gcg 6768Leu Ser Leu Asp Asp Ala Ala Arg Val Thr Ala Leu Arg Ser Gln Ala224522502255ctg gcc gca ctg gcc ggg cag ggg gcg atg gca tcg gtc ggt ctg ccg 6816Leu Ala Ala Leu Ala Gly Gln Gly Ala Met Ala Ser Val Gly Leu Pro226022652270gtc gag aag ctg gag ccg cgt ctt gcg aca tgg ggc gac cgt ctg gtc 6864Val Glu Lys Leu Glu Pro Arg Leu Ala Thr Trp Gly Asp Arg Leu Val227522802285atc gcc gcc gtg aac ggg gcg cgt tcg gcc gtg gtc tcc ggg gag ccg 6912Ile Ala Ala Val Asn Gly Ala Arg Ser Ala Val Val Ser Gly Glu Pro229022952300gaa gcg gtc gac gcc ctg gtg gag gag ctg tca cac gaa gac gta ccg 6960Glu Ala Val Asp Ala Leu Val Glu Glu Leu Ser His Glu Asp Val Pro2305 231023152320gcc cgc agg ctc atg gtc gac tgg gcg tcg cac tcc ccg cag gtc gag 7008Ala Arg Arg Leu Met Val Asp Trp Ala Ser His Ser Pro Gln Val Glu232523302335gcg atc cag ggg cgg ctg ctc gaa ctc ctc gcc ccc atc cgc gcg agg 7056Ala Ile Gln Gly Arg Leu Leu Glu Leu Leu Ala Pro Ile Arg Ala Arg234023452350acc ggc gac gtg ccc ttc tac tcc acc gtc acc ggc gaa cgc atc gac 7104Thr Gly Asp Val Pro Phe Tyr Ser Thr Val Thr Gly Glu Arg Ile Asp235523602365ggc acc gaa ctc gac gcc gac tac tgg tac cgc aac ctg cgc cag gtc 7152Gly Thr Glu Leu Asp Ala Asp Tyr Trp Tyr Arg Asn Leu Arg Gln Val237023752380gtc cgc ttc cgg gac gcg aca cag gcg ctg gtc cgc gcc ggc cac acc 7200Val Arg Phe Arg Asp Ala Thr Gln Ala Leu Val Arg Ala Gly His Thr2385 239023952400gtc ttc atc gag gcg tgc ccg cat ccg gcc gtc gcg gtc ggt gtg cag 7248Val Phe Ile Glu Ala Cys Pro His Pro Ala Val Ala Val Gly Val Gln240524102415gaa acc ctg gac gag atg ggt gac ttg gac agc ctg gtc gtc gga tct 7296Glu Thr Leu Asp Glu Met Gly Asp Leu Asp Ser Leu Val Val Gly Ser242024252430ctg cgc cgg ggc gaa ggc ggc ttg cga cgc ttc ctg atg tcc gtg gcc 7344Leu Arg Arg Gly Glu Gly Gly Leu Arg Arg Phe Leu Met Ser Val Ala243524402445gag ttg ttc gtg ggt ggg gtg gcg gtt gag tgg tcc ggt gtg ttc ggg 7392Glu Leu Phe Val Gly Gly Val Ala Val Glu Trp Ser Gly Val Phe Gly245024552460agt gtt ggt cgc ggg gtc gct ggt ggt tgc ggg gtg gag ctg ccg acg 7440Ser Val Gly Arg Gly Val Ala Gly Gly Cys Gly Val Glu Leu Pro Thr2465 247024752480tat gcg ttc gag cga gag cgc ttt tgg ctg gat gtg gag ggg gcg ccg 7488Tyr Ala Phe Glu Arg Glu Arg Phe Trp Leu Asp Val Glu Gly Ala Pro248524902495cgg ggt tcc ggg gtc tct ggg cag tgg ggt ggt cag ttg tcg gag gcg 7536Arg Gly Ser Gly Val Ser Gly Gln Trp Gly Gly Gln Leu Ser Glu Ala250025052510gtg gac acc gtg cgc ggc ggc atg ctg cgc gac tgc ctc gcc gga ctc 7584Val Asp Thr Val Arg Gly Gly Met Leu Arg Asp Cys Leu Ala Gly Leu251525202525gac ccc gcc gca cag gcc gag acc gtg ctg gac ctg gtc ctt acc cat 7632Asp Pro Ala Ala Gln Ala Glu Thr Val Leu Asp Leu Val Leu Thr His253025352540gcc gcg gcc gtc ctt gga cac ggc acc gcc gat gcg gtg gtg ccc gag 7680Ala Ala Ala Val Leu Gly His Gly Thr Ala Asp Ala Val Val Pro Glu2545 255025552560cgc gcc ttc cgc gac ctc ggt ttc gac tcc ctc acc gcc gtc gaa cta 7728Arg Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu256525702575cgc aac cgc ctc aac acc gcc acg ggc ctg cgc ttc ccg agg acc ctg 7776Arg Asn Arg Leu Asn Thr Ala Thr Gly Leu Arg Phe Pro Arg Thr Leu258025852590gtg ttc gac cat ccc cgc ccg gtg gca ctc gcg gca cac atc cac gag 7824Val Phe Asp His Pro Arg Pro Val Ala Leu Ala Ala His Ile His Glu259526002605cag ctg agc ggc gga agc ccg acc acc ggc act gcc ctt gcc ctt gcc 7872Gln Leu Ser Gly Gly Ser Pro Thr Thr Gly Thr Ala Leu Ala Leu Ala261026152620ctt cgg gcc ccg gca ccg cgt gtg gat gtc gac gag ccg att gcc att 7920Leu Arg Ala Pro Ala Pro Arg Val Asp Val Asp Glu Pro Ile Ala Ile2625 263026352640gtg ggg atg gcg tgc cgt ttt ccg ggg ggt gtg gag tcg gcg gag gat 7968Val Gly Met Ala Cys Arg Phe Pro Gly Gly Val Glu Ser Ala Glu Asp264526502655ttc tgg gag ttg atc gcg tcg ggt cgg gat gcg gtg ggg gag ttt ccg 8016Phe Trp Glu Leu Ile Ala Ser Gly Arg Asp Ala Val Gly Glu Phe Pro266026652670gtc gac cgg ggt tgg gac gtg gag gct ttc tat gat ccg gag ccg ggg 8064Val Asp Arg Gly Trp Asp Val Glu Ala Phe Tyr Asp Pro Glu Pro Gly267526802685cgg gcg ggt acg tcc tac acg cgg tgt ggt ggg ttt ttg cag ggt gcg 8112Arg Ala Gly Thr Ser Tyr Thr Arg Cys Gly Gly Phe Leu Gln Gly Ala269026952700gcg gag ttc gat gcg ggg ttt ttc ggg atc agt ccg cgt gag gcg ttg 8160Ala Glu Phe Asp Ala Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu2705 271027152720gcg atg gat ccg cag cag cgg ttg atg ctg gag gtg tcc tgg gag gcg 8208Ala Met Asp Pro Gln Gln Arg Leu Met Leu Glu Val Ser Trp Glu Ala272527302735ttg gag cgg gcg ggc atc gac ccc gcc acg ctg cac ggg tcc acg acc 8256Leu Glu Arg Ala Gly Ile Asp Pro Ala Thr Leu His Gly Ser Thr Thr274027452750ggt gtc ttc gcc ggc gtc tcg cag cag gac tac gcc gag ctc ctg cgc 8304Gly Val Phe Ala Gly Val Ser Gln Gln Asp Tyr Ala Glu Leu Leu Arg275527602765cgc ggc acc cag gac cac gag ggg tac gcg ctc acc ggc gtc tcc aac 8352Arg Gly Thr Gln Asp His Glu Gly Tyr Ala Leu Thr Gly Val Ser Asn277027752780agc gtc gtc tcc ggg cgg ctt tcc tac acc ttc ggc ttc gag ggt ccg 8400Ser Val Val Ser Gly Arg Leu Ser Tyr Thr Phe Gly Phe Glu Gly Pro2785 279027952800gcg gtg acg gtg gat acg gcg tgt tcg tcg tcg ttg gtg gcg ctg cat 8448Ala Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His280528102815ctg gcg tgt cag gcg ttg agg tcg ggg gag tgt tcg ctg gcg ttg gcg 8496Leu Ala Cys Gln Ala Leu Arg Ser Gly Glu Cys Ser Leu Ala Leu Ala282028252830ggg ggt gtg acg gtg atg tcg acg ccg ggt gcg ttt gtg gag ttc tcg 8544Gly Gly Val Thr Val Met Ser Thr Pro Gly Ala Phe Val Glu Phe Ser283528402845cgg cag cgg ggt ctg tcg ccg gac ggc cgg tgc aag gcg tac ggg tcg 8592Arg Gln Arg Gly Leu Ser Pro Asp Gly Arg Cys Lys Ala Tyr Gly Ser285028552860ggg gcc gat ggg gtc ggc tgg gcc gag ggt gtg ggt gtg ctg ttg gtg 8640Gly Ala Asp Gly Val Gly Trp Ala Glu Gly Val Gly Val Leu Leu Val2865 287028752880gag cgg ctg tcc gag gct gaa cgt cgt ggt cat cgg gtt ttg gcg gtg 8688Glu Arg Leu Ser Glu Ala Glu Arg Arg Gly His Arg Val Leu Ala Val288528902895gtg cgg ggg agt gcg gtg aat cag gac ggt gcg tcg aat ggg ttg acg 8736Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr290029052910gcg ccg aat ggt ccg tcg cag cag cgg gtg att cgg cag gcg ttg gcg 8784Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala291529202925tgt gcg ggg ttg tcc gtg gcg gat gtg gat gtg gtg gag ggg cac ggg 8832Cys Ala Gly Leu Ser Val Ala Asp Val Asp Val Val Glu Gly His Gly293029352940acg ggt acg acg ttg ggt gat ccg atc gag gcg cag gcg ttg ctc gcc 8880Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala2945 295029552960acg tac ggg cag ggt cgt tcg ggg gag cgg ccg gtg tgg ttg ggg tcg 8928Thr Tyr Gly Gln Gly Arg Ser Gly Glu Arg Pro Val Trp Leu Gly Ser296529702975gtg aag tcg aac atc ggg cat gcg cag gct gcc gcg ggt gtg gcc ggt 8976Val Lys Ser Asn Ile Gly His Ala Gln Ala Ala Ala Gly Val Ala Gly298029852990gtg atc aag atg gtc atg gcc ctg aac cac gaa ctg ttg ccg acc agc 9024Val Ile Lys Met Val Met Ala Leu Asn His Glu Leu Leu Pro Thr Ser299530003005ctg cac atc gac gaa ccc tcc ccc cac atc gac tgg tcg agc ggc ggc 9072Leu His Ile Asp Glu Pro Ser Pro His Ile Asp Trp Ser Ser Gly Gly301030153020gtc cgg ctt ctc acc gag ccc gta ccg tgg cag cag aac ggc cgg ccc 9120Val Arg Leu Leu Thr Glu Pro Val Pro Trp Gln Gln Asn Gly Arg Pro3025 303030353040agg cgc gcg ggc gtc tcc gcg ttc gga gtc agc ggg acc aac gcc cac 9168Arg Arg Ala Gly Val Ser Ala Phe Gly Val Ser Gly Thr Asn Ala His304530503055gtc atc atc gag cag gcg ccg gtc gag gcg cac gtc atc agt gag ccg 9216Val Ile Ile Glu Gln Ala Pro Val Glu Ala His Val Ile Ser Glu Pro306030653070gta ccg gct gag gcg cac gtc atc gtc gag cag gcg ccg gtc gag gcg 9264Val Pro Ala Glu Ala His Val Ile Val Glu Gln Ala Pro Val Glu Ala307530803085ccc cac gtg gtc gac gcc acc gga ccg gcg gac ctc acc gag ccg caa 9312Pro His Val Val Asp Ala Thr Gly Pro Ala Asp Leu Thr Glu Pro Gln309030953100gag gag gcg gct gaa ccg gag tgc gtc gct gac gcc gtg acc gag atg 9360Glu Glu Ala Ala Glu Pro Glu Cys Val Ala Asp Ala Val Thr Glu Met3105 311031153120tcg gct gaa ccg gag tgc gtc gcc gac gcc atg tcc gag atg tcg gct 9408Ser Ala Glu Pro Glu Cys Val Ala Asp Ala Met Ser Glu Met Ser Ala312531303135gag tgc gtc gcc gag gcc gtg tcc gac aag tcg gct gaa ccg gag tgc 9456Glu Cys Val Ala Glu Ala Val Ser Asp Lys Ser Ala Glu Pro Glu Cys314031453150gtc gcc gac gcc atg tcc gac aag ccg gcc ctc ctg ccc atc ccg tgg 9504Val Ala Asp Ala Met Ser Asp Lys Pro Ala Leu Leu Pro Ile Pro Trp315531603165ctg ctc tcc gcc aag tcc gag cga gcg ctg cgg ggc cag gcg cga cgg 9552Leu Leu Ser Ala Lys Ser Glu Arg Ala Leu Arg Gly Gln Ala Arg Arg317031753180ttg cgg cag ttc gct gcc agg gca tcc gat gcc cgg ccg gcc gac gtg 9600Leu Arg Gln Phe Ala Ala Arg Ala Ser Asp Ala Arg Pro Ala Asp Val3185 319031953200gcg cac gcc ctg gcg gca cag cgg tcc gtg ttc gat cac cgg gcc gtc 9648Ala His Ala Leu Ala Ala Gln Arg Ser Val Phe Asp His Arg Ala Val320532103215gtc gtg gcc gag gac cgc gac ggc ttc ctt cag gcc ctc gac gcg ctg 9696Val Val Ala Glu Asp Arg Asp Gly Phe Leu Gln Ala Leu Asp Ala Leu322032253230gcc gag ggc cgg tcg gcg gac ggc ctg atc gaa ggg tcg gtc ggc ccg 9744Ala Glu Gly Arg Ser Ala Asp Gly Leu Ile Glu Gly Ser Val Gly Pro323532403245cgt ggc ggc cac tca ggc cgc cgg cgc gga aag acc gcc atg ctg ttc 9792Arg Gly Gly His Ser Gly Arg Arg Arg Gly Lys Thr Ala Met Leu Phe325032553260gcc gga cag ggc acg caa cgc gtg gga atg ggc cgt cag ctg tat gcg 9840Ala Gly Gln Gly Thr Gln Arg Val Gly Met Gly Arg Gln Leu Tyr Ala3265 327032753280gct cac ccg gcc tac gcg gac gcg ctg gac cag gta ctg gcg gaa ctg 9888Ala His Pro Ala Tyr Ala Asp Ala Leu Asp Gln Val Leu Ala Glu Leu328532903295gac ggt cac ctg gac cag ccc ctg cgc ccg ctg atc cac gcc agt gcg 9936Asp Gly His Leu Asp Gln Pro Leu Arg Pro Leu Ile His Ala Ser Ala330033053310gat ctt gcg gat gtc gcg gat gcc gcg gat gtt ctg gac cgt acg cgg 9984Asp Leu Ala Asp Val Ala Asp Ala Ala Asp Val Leu Asp Arg Thr Arg331533203325tac gcc cag ccg gcg ctg ttc gcc gtc cag gtc gcg ctc ttc cgg cac 10032Tyr Ala Gln Pro Ala Leu Phe Ala Val Gln Val Ala Leu Phe Arg His333033353340ctg gaa cgt ctc ggc gtg cgc gcg gac ttc gtg gcc ggg cac tcg atc 10080Leu Glu Arg Leu Gly Val Arg Ala Asp Phe Val Ala Gly His Ser Ile3345 335033553360ggc gag ctc gcg gcc gcc cac gtc gcc ggg gtg ctt ccc ctg gca gca 10128Gly Glu Leu Ala Ala Ala His Val Ala Gly Val Leu Pro Leu Ala Ala336533703375gcc tgc cgc ctg gtg gcg gcc cgc ggg cgc ctg atg gag cag ctc gca 10176Ala Cys Arg Leu Val Ala Ala Arg Gly Arg Leu Met Glu Gln Leu Ala338033853390cca ggc ggc gcc atg gtc gcc gta cgg gcg agc gaa gcc gag gcg cga 10224Pro Gly Gly Ala Met Val Ala Val Arg Ala Ser Glu Ala Glu Ala Arg339534003405cag gcg ctc gac ggc cgg gaa gcc cgg gtg tcg gtc gcg gcc gtg aac 10272Gln Ala Leu Asp Gly Arg Glu Ala Arg Val Ser Val Ala Ala Val Asn341034153420gga ccc gcc tcg gtg gtg ttc tcc ggc gcc gag gac gag gtg ggg aac 10320Gly Pro Ala Ser Val Val Phe Ser Gly Ala Glu Asp Glu Val Gly Asn3425 343034353440atg gcg gac tgg ttc gcc gag cgc ggg cgg aga gtc aag cgc ctg cga 10368Met Ala Asp Trp Phe Ala Glu Arg Gly Arg Arg Val Lys Arg Leu Arg344534503455acc ggg cat gcc ttc cac tca ccg ctg atg gac ccg atg ctg gag gag 10416Thr Gly His Ala Phe His Ser Pro Leu Met Asp Pro Met Leu Glu Glu346034653470ttc cag cag gtc gcg gcc tcg ctg acc tac agc gaa cca gcc att ccc 10464Phe Gln Gln Val Ala Ala Ser Leu Thr Tyr Ser Glu Pro Ala Ile Pro347534803485atg gtg tcg acg ctc acc ggc gac atc gtg gcg gcg gga gaa ctg agc 10512Met Val Ser Thr Leu Thr Gly Asp Ile Val Ala Ala Gly Glu Leu Ser349034953500gac ccc gag tac tgg gtc cgg cag gta cgg cgg acc gtg cgc ttc ggc 10560Asp Pro Glu Tyr Trp Val Arg Gln Val Arg Arg Thr Val Arg Phe Gly3505 351035153520gac gcg atc agc cgc ctg cac acc gac gga gtc cgc acc ttc atg gaa 10608Asp Ala Ile Ser Arg Leu His Thr Asp Gly Val Arg Thr Phe Met Glu352535303535ctg ggc cca gac ggg acc ctg tcg gca ctg gcc gag gaa tgc cta gag 10656Leu Gly Pro Asp Gly Thr Leu Ser Ala Leu Ala Glu Glu Cys Leu Glu3540 3545 3550gcc acc gcc gac agc cac ccc gcc gac gac gac acc ggc acc ccg caa 10704Ala Thr Ala Asp Ser His Pro Ala Asp Asp Asp Thr Gly Thr Pro Gln355535603565gag aac ctg ctc atc ccg ctc cta cgg ccg gac agc ccg gaa ccc ggc 10752Glu Asn Leu Leu Ile Pro Leu Leu Arg Pro Asp Ser Pro Glu Pro Gly357035753580acc ctg ctc acc ggc ttg gcc cgg ctg cat acg cac gga gcg gcg gcg 10800Thr Leu Leu Thr Gly Leu Ala Arg Leu His Thr His Gly Ala Ala Ala3585 359035953600gtc aac tgg ccc gcc gcc ctg ccc gaa cgc gat cga gcc cgc cac ctc 10848Val Asn Trp Pro Ala Ala Leu Pro Glu Arg Asp Arg Ala Arg His Leu360536103615gac ctg ccg acc tac gcc ttc gat cac cac cgc tac tgg gtc gac acc 10896Asp Leu Pro Thr Tyr Ala Phe Asp His His Arg Tyr Trp Val Asp Thr362036253630tcg gcc ggc cac ccg ggg gac ctg tcg gca gcg ggg ctc ggc acc gcc 10944Ser Ala Gly His Pro Gly Asp Leu Ser Ala Ala Gly Leu Gly Thr Ala363536403645ggg cat ccc ctg ctc ggt tcc gcg gtg gca ctg gcc gag tcg cag gaa 10992Gly His Pro Leu Leu Gly Ser Ala Val Ala Leu Ala Glu Ser Gln Glu365036553660ctc ctc ttc acc ggc cgt ctc tcc ctg cgc aca cac ccg tgg ctg gcc 11040Leu Leu Phe Thr Gly Arg Leu Ser Leu Arg Thr His Pro Trp Leu Ala3665 367036753680gac cac gcc atc ttc ggt acc gtc ctg ctg ccc ggc acg gcc atc ctg 11088Asp His Ala Ile Phe Gly Thr Val Leu Leu Pro Gly Thr Ala Ile Leu368536903695gaa ctg gcc gtg cgc gca ggc gac gag gtc gac tgc ggc acc gtc gag 11136Glu Leu Ala Val Arg Ala Gly Asp Glu Val Asp Cys Gly Thr Val Glu370037053710gaa ctc acc ctg cgg aca ccg ctc gtc ctt ccc gaa cag ggc tcg gtg 11184Glu Leu Thr Leu Arg Thr Pro Leu Val Leu Pro Glu Gln Gly Ser Val371537203725atc ctg caa ctc tcc gtc ggg gca ccc cag ggc ccc cag acg ccc gag 11232Ile Leu Gln Leu Ser Val Gly Ala Pro Gln Gly Pro Gln Thr Pro Glu373037353740gag ccc gaa cgg cgc acc ttc gcc ctg tac gcc cgc gaa gac gac gga 11280Glu Pro Glu Arg Arg Thr Phe Ala Leu Tyr Ala Arg Glu Asp Asp Gly3745 375037553760ctg tcg tcc tcg tcc gcg gcg gcg acc ggc acc gag tgg acc tgc cac 11328Leu Ser Ser Ser Ser Ala Ala Ala Thr Gly Thr Glu Trp Thr Cys His376537703775gcc acc ggc gtc ctg acc ggc acc gcc cgg ccc gcg gag gag cac aca 11376Ala Thr Gly Val Leu Thr Gly Thr Ala Arg Pro Ala Glu Glu His Thr378037853790cag gaa ccg tgg ccg ccc gcc gac gca gca ccg gtg gac ctg gac ggc 11424Gln Glu Pro Trp Pro Pro Ala Asp Ala Ala Pro Val Asp Leu Asp Gly379538003805tgg tac gag cag ctg gcc ggc gcc ggc ctg gga tac ggg ccg gtg ttc 11472Trp Tyr Glu Gln Leu Ala Gly Ala Gly Leu Gly Tyr Gly Pro Val Phe381038153820cag ggg ctg cgc gag gtc tgg cgg cgc ggg gac gag gtg ttc gcc gtc 11520Gln Gly Leu Arg Glu Val Trp Arg Arg Gly Asp Glu Val Phe Ala Val3825 383038353840gtc acc ctg ccc gag agc acg gag gga cag gcg gcc gac gcc gcc cgg 11568Val Thr Leu Pro Glu Ser Thr Glu Gly Gln Ala Ala Asp Ala Ala Arg384538503855tac gcc ctg cac ccg gcc ctg ctg gac gcg gca ctg cac ccg gtc gtt 11616Tyr Ala Leu His Pro Ala Leu Leu Asp Ala Ala Leu His Pro Val Val386038653870ctg cgc cac gag ggc gat gcc gcc gcc gac gga cac ggc tgg ctg ccg 11664Leu Arg His Glu Gly Asp Ala Ala Ala Asp Gly His Gly Trp Leu Pro387538803885ttc tcc tgg acc ggc gtc acg gtc gcc gcc tcc ggc gcc tcc acc ctg 11712Phe Ser Trp Thr Gly Val Thr Val Ala Ala Ser Gly Ala Ser Thr Leu389038953900cac gtc cgt ctc acc gtc cgc acg gac gag gac gcg gtc gga ctg ctg 11760His Val Arg Leu Thr Val Arg Thr Asp Glu Asp Ala Val Gly Leu Leu3905 391039153920gcc acc gac gca tcg gga cgc atc gtc atc tcc gcg ggg tcc ctc gcc 11808Ala Thr Asp Ala Ser Gly Arg Ile Val Ile Ser Ala Gly Ser Leu Ala392539303935ttc cgg ccc gtc tcc gcc gag cag ctc cag gcc gcg cgc acc ggc tac 11856Phe Arg Pro Val Ser Ala Glu Gln Leu Gln Ala Ala Arg Thr Gly Tyr394039453950cac gac cac ctc ttc cgc atc gaa tgg cgg ccg ctg cac ctc ccc acc 11904His Asp His Leu Phe Arg Ile Glu Trp Arg Pro Leu His Leu Pro Thr395539603965aca ccg gca cgg aca gcc gac tgg gcc cta atc ggc ccc ggt gcc cgg 11952Thr Pro Ala Arg Thr Ala Asp Trp Ala Leu Ile Gly Pro Gly Ala Arg397039753980cgg acg gcc gcc gtc ctg gag cgc aac ggc gcc tcc tgg cag gcc tac 12000Arg Thr Ala Ala Val Leu Glu Arg Asn Gly Ala Ser Trp Gln Ala Tyr3985 399039954000ccg gac ccg gcg gct ctc gca gaa gcc ctg gcg gcc ggc gcc ccg gca 12048Pro Asp Pro Ala Ala Leu Ala Glu Ala Leu Ala Ala Gly Ala Pro Ala400540104015ccg ggc atg gtc gtc atc tcg tgc gag ccg gac ggc gca tcc gcc ccc 12096Pro Gly Met Val Val Ile Ser Cys Glu Pro Asp Gly Ala Ser Ala Pro402040254030acc gat tcc gcc ctc acc gat tcc gcc ctc acc gat tcc gcc ccg gcc 12144Thr Asp Ser Ala Leu Thr Asp Ser Ala Leu Thr Asp Ser Ala Pro Ala403540404045ggc tcg gcc ccg gcc gac tcc acc gcc ctc gcc gac gcc acc cgg caa 12192Gly Ser Ala Pro Ala Asp Ser Thr Ala Leu Ala Asp Ala Thr Arg Gln405040554060gcc acc acc cgc gtc ctc gcc ctg ctc cag gaa tgg gtc gcc gac gaa 12240Ala Thr Thr Arg Val Leu Ala Leu Leu Gln Glu Trp Val Ala Asp Glu4065 407040754080cgg ctc gcg gcc tgc cgc ctg gcc ctc ctc acg cac ggc tcg gtc acc 12288Arg Leu Ala Ala Cys Arg Leu Ala Leu Leu Thr His Gly Ser Val Thr408540904095gcg acc ccc gac gag ccc gtg tcc gac ctc gca cac gcc gcc gtc tgg 12336Ala Thr Pro Asp Glu Pro Val Ser Asp Leu Ala His Ala Ala Val Trp410041054110gga ctg gtc cgc tcc gtg cag acc gag aac ccc gac cgg ttc ctg ctg 12384Gly Leu Val Arg Ser Val Gln Thr Glu Asn Pro Asp Arg Phe Leu Leu411541204125gcc gac acc gac gac acc gac gcc tcc cgc aac gcc ctt ccc ctg ctg 12432Ala Asp Thr Asp Asp Thr Asp Ala Ser Arg Asn Ala Leu Pro Leu Leu413041354140gcc ggg gaa ccg cag atc gcc ctg cga aat ggt gcc gtc cgc atc ccg 12480Ala Gly Glu Pro Gln Ile Ala Leu Arg Asn Gly Ala Val Arg Ile Pro4145 415041554160cgg atg aca cga gtg ccc gtc cgg cag cca cag ccg agc acc acc gac 12528Arg Met Thr Arg Val Pro Val Arg Gln Pro Gln Pro Ser Thr Thr Asp416541704175gcc gac tgg gac ccg gag gcc acg gtc ctc atc acg ggc ggt acc ggc 12576Ala Asp Trp Asp Pro Glu Ala Thr Val Leu Ile Thr Gly Gly Thr Gly418041854190gtc ctc ggc cgg ctc gtc gcc cgt cat ctc gcc acg gcc cac ggg gta 12624Val Leu Gly Arg Leu Val Ala Arg His Leu Ala Thr Ala His Gly Val419542004205cgg cac ctg ctg ctg gcc acc cgc cgc ggc acg gcc gcg gac ggc gcc 12672Arg His Leu Leu Leu Ala Thr Arg Arg Gly Thr Ala Ala Asp Gly Ala421042154220gcc gac ctg gtc gcc gaa ctc gcc ggc ctc ggc gcc gag gcc acg gtc 12720Ala Asp Leu Val Ala Glu Leu Ala Gly Leu Gly Ala Glu Ala Thr Val4225 423042354240gcg gcc tgc gac atc ggg gac cgg gcg gcc gtc gcc gcg ctc ctc gac 12768Ala Ala Cys Asp Ile Gly Asp Arg Ala Ala Val Ala Ala Leu Leu Asp424542504255caa gtg ccc gcg cag cac ccc ctg aaa gcc gtg atc cac acg gcc ggt 12816Gln Val Pro Ala Gln His Pro Leu Lys Ala Val Ile His Thr Ala Gly426042654270gtg gtc gac gac ggc atc ctc acc tcg ctc act ccg gag cgc atg gag 12864Val Val Asp Asp Gly Ile Leu Thr Ser Leu Thr Pro Glu Arg Met Glu427542804285gcc gtc ctg cac gcg aag gcg ttc ggc gcc gcg cac ctg cac gac ctg 12912Ala Val Leu His Ala Lys Ala Phe Gly Ala Ala His Leu His Asp Leu429042954300acc cgc gac gcc ggc ctc acc acc ttc acc gtc ttc tcc tcg gcc gcc 12960Thr Arg Asp Ala Gly Leu Thr Thr Phe Thr Val Phe Ser Ser Ala Ala4305 431043154320gcc tcc ttc ggc agt ccc gga cag ggc aac tac acc gcg gcg aac gcc 13008Ala Ser Phe Gly Ser Pro Gly Gln Gly Asn Tyr Thr Ala Ala Asn Ala432543304335ttt ctg gac gcc ctg atg cag cac cgc cac acc cag gca ctg ccg ggc 13056Phe Leu Asp Ala Leu Met Gln His Arg His Thr Gln Ala Leu Pro Gly434043454350cgg tcg ctc gcc tgg ggc ctt tgg ggc gag gcc gac ggc atg acc cgc 13104Arg Ser Leu Ala Trp Gly Leu Trp Gly Glu Ala Asp Gly Met Thr Arg435543604365aac ctc gcc ggc acc gac ttc gcg cgc atg gcc cgc ggc ggc ctg ctc 13152Asn Leu Ala Gly Thr Asp Phe Ala Arg Met Ala Arg Gly Gly Leu Leu437043754380ccc ctg tcc aac gca cag gga ctc gcg ctc ctc gac aca gcg gat cgc 13200Pro Leu Ser Asn Ala Gln Gly Leu Ala Leu Leu Asp Thr Ala Asp Arg4385 439043954400ctc ggc cct ttc ggt gac ggg ctg ctc ctc gcc acc cgg ctc gac gcg 13248Leu Gly Pro Phe Gly Asp Gly Leu Leu Leu Ala Thr Arg Leu Asp Ala440544104415gcc acc ctc cac gca cag gcc acg gcc ggc gcc ctg ccg cgc atc ctg 13296Ala Thr Leu His Ala Gln Ala Thr Ala Gly Ala Leu Pro Arg Ile Leu442044254430cac ggg ctg atc cgc atc ccg gcc cgg cgg tcc gcc gac cac ggc atc 13344His Gly Leu Ile Arg Ile Pro Ala Arg Arg Ser Ala Asp His Gly Ile443544404445gcg acc gac acc ccc gcc acg ctg cgc gag cgc ctg gcc gga ctc acc 13392Ala Thr Asp Thr Pro Ala Thr Leu Arg Glu Arg Leu Ala Gly Leu Thr445044554460atc ccc gcg cag cgc acc ggt ctc ctc ctg gaa ctc gta cgg acc cat 13440Ile Pro Ala Gln Arg Thr Gly Leu Leu Leu Glu Leu Val Arg Thr His4465 447044754480gcc gcc gcc gtc ctc ggc cac ccc acc agc gcc gtc aca gcc gcg gac 13488Ala Ala Ala Val Leu Gly His Pro Thr Ser Ala Val Thr Ala Ala Asp4485 44904495ggc gca ctc ccg gac gat ctg gtc ccg gcc gac acc gag ttc cgc gac 13536Gly Ala Leu Pro Asp Asp Leu Val Pro Ala Asp Thr Glu Phe Arg Asp450045054510ctc ggc ttc gac tcg ctg acc gcc gtc gaa ctc cgc aac cgg atc aac 13584Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu Arg Asn Arg Ile Asn451545204525gcc gtc acc ggc ctg cgc ctc ccg gca acg ctc atc ttc gac cag ccc 13632Ala Val Thr Gly Leu Arg Leu Pro Ala Thr Leu Ile Phe Asp Gln Pro453045354540agc ccc gcg gca ctc gcc gat cac ctc gcg acc cgc ctg acg gcc gag 13680Ser Pro Ala Ala Leu Ala Asp His Leu Ala Thr Arg Leu Thr Ala Glu4545 455045554560gcg ggc acg ccg gac gag ccg gcc cct gcc gcc gcg gca gcc ggg gcc 13728Ala Gly Thr Pro Asp Glu Pro Ala Pro Ala Ala Ala Ala Ala Gly Ala456545704575ggg agc gca ggg agt gcc gag acc gga cag cag cgc agt acg ggg agc 13776Gly Ser Ala Gly Ser Ala Glu Thr Gly Gln Gln Arg Ser Thr Gly Ser458045854590gag aag cag cag acc agg ggc ggc acc tcc acc gaa acc gtc gaa tcc 13824Glu Lys Gln Gln Thr Arg Gly Gly Thr Ser Thr Glu Thr Val Glu Ser459546004605ctg ttc tgg atc gga cac gac acc cgc cgc atc gag gag tcc atg gcc 13872Leu Phe Trp Ile Gly His Asp Thr Arg Arg Ile Glu Glu Ser Met Ala461046154620ctg ctc tcg gcg gcc tcc ttc ttc cgg ccc gcc ttc acg gac ccc tcg 13920Leu Leu Ser Ala Ala Ser Phe Phe Arg Pro Ala Phe Thr Asp Pro Ser4625 463046354640gac atc ccg gag ccg acg ttc gtc cgg ctc gcc cag ggt gaa gcg cgc 13968Asp Ile Pro Glu Pro Thr Phe Val Arg Leu Ala Gln Gly Glu Ala Arg464546504655gcc caa ggt gaa gca ctc gcc cgg ggc gaa aca cgg ccc gcc ctc atc 14016Ala Gln Gly Glu Ala Leu Ala Arg Gly Glu Thr Arg Pro Ala Leu Ile466046654670tgc ctg ccc acc gtc gcc gcc gtg tcg agc gtg tac cag tac tca cgt 14064Cys Leu Pro Thr Val Ala Ala Val Ser Ser Val Tyr Gln Tyr Ser Arg467546804685ttc gcg gcg gga ctg aac gga cac cga gac gtc tgg tac gtt cct gcg 14112Phe Ala Ala Gly Leu Asn Gly His Arg Asp Val Trp Tyr Val Pro Ala469046954700cca ggg ttc ctg gag ggc gaa ccc ctg ccg tcc gga atc ggc gcg gtg 14160Pro Gly Phe Leu Glu Gly Glu Pro Leu Pro Ser Gly Ile Gly Ala Val4705 471047154720acc cgc atg ttc gcc gac gcg atc gtc cgg ttc acc gac ggc gcg cct 14208Thr Arg Met Phe Ala Asp Ala Ile Val Arg Phe Thr Asp Gly Ala Pro472547304735ttt gcg ctc gcc ggg cat tcc gcg ggc gga tgg ttc gtc tac gcg gtg 14256Phe Ala Leu Ala Gly His Ser Ala Gly Gly Trp Phe Val Tyr Ala Val474047454750acg agt cat ctg gag cgt cta ggc gtc cgt ccg gaa gcg gtg gtg acc 14304Thr Ser His Leu Glu Arg Leu Gly Val Arg Pro Glu Ala Val Val Thr475547604765atg gac gcc tat ctc ccg gac gac ggc atc gca cct gtc gcg tcc gcg 14352Met Asp Ala Tyr Leu Pro Asp Asp Gly Ile Ala Pro Val Ala Ser Ala477047754780ctg aca agt gaa atc ttc gac cgc gtc acg cag ttt gtg gac gtg gac 14400Leu Thr Ser Glu Ile Phe Asp Arg Val Thr Gln Phe Val Asp Val Asp4785 479047954800tac aca cgc ctg gtc gcc atg ggc gga tac ttc cgc atc ttc tcc ggc 14448Tyr Thr Arg Leu Val Ala Met Gly Gly Tyr Phe Arg Ile Phe Ser Gly480548104815tgg agt cct ccg gac atc acc aca ccc gcc ctc ttc ctg cgc ggc cgg 14496Trp Ser Pro Pro Asp Ile Thr Thr Pro Ala Leu Phe Leu Arg Gly Arg482048254830gac gga gaa cag atg ccg ccg ccg tgg gga gtt ccg cac acc gtt ctg 14544Asp Gly Glu Gln Met Pro Pro Pro Trp Gly Val Pro His Thr Val Leu483548404845gac atc cag ggg aat cac ttc acg atg ctg gaa cag ttt gcg gat tcg 14592Asp Ile Gln Gly Asn His Phe Thr Met Leu Glu Gln Phe Ala Asp Ser485048554860act gct cgg cat gtc gac gaa tgg ctg aca gaa atc gca tca gtg cgg 14640Thr Ala Arg His Val Asp Glu Trp Leu Thr Glu Ile Ala Ser Val Arg4865 487048754880cgc tgatcgcgcc tctgatcgcg gtcctgatcg cggccctgat cggcgggtcg14693Argggcacagccc ggtcggccgg tcggccagtc ggccagtcgg tggtatccgg tcggctccgg 14753catcgatcag tgctttcccc cttacggcca tacgggcctt tctgagactt cttgaatttg 14813ggagacagtg atg gac acg tcc agc gaa aag ctc gtc gac gcg ctt agg14862Met Asp Thr Ser Ser Glu Lys Leu Val Asp Ala Leu Arg48854890gcg tct ctg aag gcg aac cag acc ctg cgg gca cgt aat gag caa ctg 14910Ala Ser Leu Lys Ala Asn Gln Thr Leu Arg Ala Arg Asn Glu Gln Leu4895 490049054910gca gcc gcc atg gag gcg tcc agc gag ccg att gcg att gtg ggg atg 14958Ala Ala Ala Met Glu Ala Ser Ser Glu Pro Ile Ala Ile Val Gly Met491549204925gcg tgt cgt ttt ccg ggt ggg gtg tgt tcg ccg gag gag ttg tgg gag 15006Ala Cys Arg Phe Pro Gly Gly Val Cys Ser Pro Glu Glu Leu Trp Glu493049354940ctg gtt gcg tcg ggt ggg gat gcg att ggt gaa ttt ccg gcc ggt cgg 15054Leu Val Ala Ser Gly Gly Asp Ala Ile Gly Glu Phe Pro Ala Gly Arg494549504955ggg tgg gat ctg gag ggg ttg ttt gat tcg gac cct gac cgg tcg ggg 15102Gly Trp Asp Leu Glu Gly Leu Phe Asp Ser Asp Pro Asp Arg Ser Gly496049654970acg tcg tac gcg cgg tat ggc ggg ttt ttg tat gag gcg ggg gag ttc 15150Thr Ser Tyr Ala Arg Tyr Gly Gly Phe Leu Tyr Glu Ala Gly Glu Phe4975 498049854990gat gcg gac ttc ttc ggg atc agt ccg cgt gag gcg ttg gcg atg gat 15198Asp Ala Asp Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp499550005005ccg cag cag cgg ttg ttg ctg gag acg tcg tgg gag gcg ttc gag cgg 15246Pro Gln Gln Arg Leu Leu Leu Glu Thr Ser Trp Glu Ala Phe Glu Arg501050155020gcg ggt atc gat ccg ctg tcg atg cgt ggc tcc cgt acg ggt gtc ttc 15294Ala Gly Ile Asp Pro Leu Ser Met Arg Gly Ser Arg Thr Gly Val Phe502550305035gcc ggg gtg atg tac cac gac tac gga tcc cgc ctg ggt acc atc ccc 15342Ala Gly Val Met Tyr His Asp Tyr Gly Ser Arg Leu Gly Thr Ile Pro504050455050gag gga ttc gag ggc tac atc ggc aac ggt agc ggc ggc gcc gtc gcg 15390Glu Gly Phe Glu Gly Tyr Ile Gly Asn Gly Ser Gly Gly Ala Val Ala5055 506050655070tcg ggc cgc gtc gcc tac acg ctc ggt ctc gag ggc cct gcc gtc tcg 15438Ser Gly Arg Val Ala Tyr Thr Leu Gly Leu Glu Gly Pro Ala Val Ser507550805085gtg gac acg gca tgt tcg tcg tcg ttg gtg gcg ctg cat ctg gcg tgc 15486Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys509050955100cag tcg ctg cgg tcg ggt gag tgc acg ctc gcg ctg gcc ggc ggt gtg 15534Gln Ser Leu Arg Ser Gly Glu Cys Thr Leu Ala Leu Ala Gly Gly Val510551105115acg gtg atg tcg acc ccg cac ctc ttc gtc gag ttc tca cgc cag cgc 15582Thr Val Met Ser Thr Pro His Leu Phe Val Glu Phe Ser Arg Gln Arg512051255130gga ctg tcg gtg gac ggc cgc tgc aag tcc ttc gcg ggt gga gcc gac 15630Gly Leu Ser Val Asp Gly Arg Cys Lys Ser Phe Ala Gly Gly Ala Asp5135 514051455150ggc acc ggc atg ggc gag ggc gtc ggg atg ctg ttg gtg gag cgg ttg 15678Gly Thr Gly Met Gly Glu Gly Val Gly Met Leu Leu Val Glu Arg Leu515551605165tcg gat gcg gtg cgg ctg ggg cat cgg gtg ctg gcg gtg ctg cgc ggc 15726Ser Asp Ala Val Arg Leu Gly His Arg Val Leu Ala Val Leu Arg Gly517051755180agt gcg gtc aat cag gac ggt gcg tcg aat ggg ttg acg gcg ccg aat 15774Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn518551905195ggt ccg gct cag gag cgg gtg atc cgg cag gcg ttg gcg aac gcg ggg 15822Gly Pro Ala Gln Glu Arg Val Ile Arg Gln Ala Leu Ala Asn Ala Gly520052055210ttg tcc gtg gcg gat gtg gat gtg gtg gag ggg cat ggg acg ggc acg 15870Leu Ser Val Ala Asp Val Asp Val Val Glu Gly His Gly Thr Gly Thr5215 522052255230acg ctg ggt gat ccg atc gag gcg cag gcg ttg ctc gcc acg tac ggg 15918Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly523552405245cag cgg gcc ggt aac agg ccg ctg tgg ctg gga tcg gtg aag tcg aac 15966Gln Arg Ala Gly Asn Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn525052555260atc ggc cat gcg cag gct gcc gcg ggt gtg ggt ggg gtc atc aag atg 16014Ile Gly His Ala Gln Ala Ala Ala Gly Val Gly Gly Val Ile Lys Met526552705275gtg atg gcg ttg cgg gag ggg gtg ttg ccg cgg acg ttg cat gtg gat 16062Val Met Ala Leu Arg Glu Gly Val Leu Pro Arg Thr Leu His Val Asp528052855290gag ccg tcg ccg cag gtg gac tgg tcc gcg ggg gcg gtg cgg ctg ctg 16110Glu Pro Ser Pro Gln Val Asp Trp Ser Ala Gly Ala Val Arg Leu Leu5295 530053055310acg gag gcg gtg ccg tgg ccg ggg gac gcg gca ggg cgg ttg cgg cgg 16158Thr Glu Ala Val Pro Trp Pro Gly Asp Ala Ala Gly Arg Leu Arg Arg531553205325gcg gga gtg tcg tcg ttc ggg gtc agt ggc acg aat gcg cat gtg att 16206Ala Gly Val Ser Ser Phe Gly Val Ser Gly Thr Asn Ala His Val Ile533053355340ttg gag gag gcg ccg gcg gcg ggg ggc tgt gtt gcc ggg ggt ggg gtg 16254Leu Glu Glu Ala Pro Ala Ala Gly Gly Cys Val Ala Gly Gly Gly Val534553505355ttg gag ggt gct ccg ggt ctt gcc att tcg gtg gct gag tcg gtg gcc 16302Leu Glu Gly Ala Pro Gly Leu Ala Ile Ser Val Ala Glu Ser Val Ala536053655370gct cca gtg gct gtg tct gcg ccg gtg gct gag tcg gtg ccg gtg ccg 16350Ala Pro Val Ala Val Ser Ala Pro Val Ala Glu Ser Val Pro Val Pro5375 538053855390gtg ccg gtg ccg gtt cct gtg ccg gtg tcg gct agg tct gag gct ggg 16398Val Pro Val Pro Val Pro Val Pro Val Ser Ala Arg Ser Glu Ala Gly539554005405ttg cgg gcg cag gcg gag gcg ttg cgt cag tac gtg gca gtc cgg ccg 16446Leu Arg Ala Gln Ala Glu Ala Leu Arg Gln Tyr Val Ala Val Arg Pro54105415 5420gac gtt tcg ctt gcc gat gtg ggt gcg ggt ctg gcc tgt ggg cgg gct 16494Asp Val Ser Leu Ala Asp Val Gly Ala Gly Leu Ala Cys Gly Arg Ala542554305435gtg ctg gag cat cgt gcg gtc gtc ctg gcc gcg gac cgt gag gag ctg 16542Val Leu Glu His Arg Ala Val Val Leu Ala Ala Asp Arg Glu Glu Leu544054455450gtg caa ggg ttg ggg gcg ctg gcg gcg ggt gag ccg gat cgg cgg gtg 16590Val Gln Gly Leu Gly Ala Leu Ala Ala Gly Glu Pro Asp Arg Arg Val5455 5460 54655470acc acg ggt cat gcg ccg ggt ggt gac cgg ggc ggt gtc gtc ttc gtg 16638Thr Thr Gly His Ala Pro Gly Gly Asp Arg Gly Gly Val Val Phe Val547554805485ttt ccc gga cag ggt ggg cag tgg gcc ggg atg ggt gtg cgt ctg ctc 16686Phe Pro Gly Gln Gly Gly Gln Trp Ala Gly Met Gly Val Arg Leu Leu549054955500gcc tcc tct ccg gtg ttc gcc cgg cgg atg cag gcg tgc gag gag gct 16734Ala Ser Ser Pro Val Phe Ala Arg Arg Met Gln Ala Cys Glu Glu Ala550555105515ctg gcg ccg tgg gtg gac tgg tct gtg gtg gac atc ctg cgc cgg gac 16782Leu Ala Pro Trp Val Asp Trp Ser Val Val Asp Ile Leu Arg Arg Asp552055255530gcg ggg gat gcg gtg tgg gag cgg gcc gat gtg gtc cag cct gtg ctg 16830Ala Gly Asp Ala Val Trp Glu Arg Ala Asp Val Val Gln Pro Val Leu5535 554055455550ttc agc gtc atg gtg tct ttg gct gct ctg tgg cgt tcc tac ggt atc 16878Phe Ser Val Met Val Ser Leu Ala Ala Leu Trp Arg Ser Tyr Gly Ile555555605565gaa ccc gac gcg gtc ctt ggc cat tcc cag ggc gag atc gcg gcc gcg 16926Glu Pro Asp Ala Val Leu Gly His Ser Gln Gly Glu Ile Ala Ala Ala557055755580cat gtg tgt ggg gcg ctg agc ctg aag gac gcg gcg aag act gtt gcg 16974His Val Cys Gly Ala Leu Ser Leu Lys Asp Ala Ala Lys Thr Val Ala558555905595ctg cgc agc cgg gcg ctg gcc gct gtg cgg ggc cgg ggc ggc atg gcc 17022Leu Arg Ser Arg Ala Leu Ala Ala Val Arg Gly Arg Gly Gly Met Ala560056055610tca gtg ccg ctg cct gcc cag gag gtg gag cag ctc att ggt gag cgg 17070Ser Val Pro Leu Pro Ala Gln Glu Val Glu Gln Leu Ile Gly Glu Arg5615 562056255630tgg gcg ggg cgg ttg tgg gtg gcg gcg gtc aac ggc ccc cgc tcc acc 17118Trp Ala Gly Arg Leu Trp Val Ala Ala Val Asn Gly Pro Arg Ser Thr563556405645gcc gtc tcg ggg gat gcc gag gcg gtg gac gag gtg ctg gcg tac tgt 17166Ala Val Ser Gly Asp Ala Glu Ala Val Asp Glu Val Leu Ala Tyr Cys565056555660gcc ggc acc ggg gtg cgg gcc cgg cgg atc ccg gtc gac tat gcc tcg 17214Ala Gly Thr Gly Val Arg Ala Arg Arg Ile Pro Val Asp Tyr Ala Ser566556705675cac tgc ccc cat gtg cag ccc ctg cgg gag gag ttg ctg gag ctg ctg 17262His Cys Pro His Val Gln Pro Leu Arg Glu Glu Leu Leu Glu Leu Leu568056855690ggg gac atc agc ccg cag ccg tcc ggc gtg ccg ttc ttc tcc acg gtg 17310Gly Asp Ile Ser Pro Gln Pro Ser Gly Val Pro Phe Phe Ser Thr Val5695 570057055710gag ggc acc tgg ctg gac acc aca acc ctg gac gcc gcc tac tgg tac 17358Glu Gly Thr Trp Leu Asp Thr Thr Thr Leu Asp Ala Ala Tyr Trp Tyr571557205725cgc aac ctg cac cag cct gtc cgt ttc agc gat gcc gtc cag gcc ctg 17406Arg Asn Leu His Gln Pro Val Arg Phe Ser Asp Ala Val Gln Ala Leu573057355740gcg gat gac gga cac cgc gtc ttc gtc gaa gtc agc ccc cac ccc acc 17454Ala Asp Asp Gly His Arg Val Phe Val Glu Val Ser Pro His Pro Thr574557505755ctc gtc ccc gcc atc gaa gac acc acc gaa gac acc gcc gaa gac gtc 17502Leu Val Pro Ala Ile Glu Asp Thr Thr Glu Asp Thr Ala Glu Asp Val576057655770acc gcg atc ggc agc ctc cgc cgc ggc gac aac gac acc cgc cgc ttc 17550Thr Ala Ile Gly Ser Leu Arg Arg Gly Asp Asn Asp Thr Arg Arg Phe5775 578057855790ctc acc gcc ctc gcc cac acc cac acc acc ggc atc ggc aca ccc acc 17598Leu Thr Ala Leu Ala His Thr His Thr Thr Gly Ile Gly Thr Pro Thr579558005805acc tgg cac cac cac tac acc cac cac cac acc cac ccc cac aac cac 17646Thr Trp His His His Tyr Thr His His His Thr His Pro His Asn His581058155820cac ctc gac ctc ccc act tat ccc ttc caa cgc cag cac tac tgg ctc 17694His Leu Asp Leu Pro Thr Tyr Pro Phe Gln Arg Gln His Tyr Trp Leu582558305835gac gct ccc acg gga gca ggt gac gtc gcc gct gct ggc ttg gag ccg 17742Asp Ala Pro Thr Gly Ala Gly Asp Val Ala Ala Ala Gly Leu Glu Pro584058455850gcc gaa cac cct ctg ctc gcg gca aca gtc caa ctc gca gac acg gac 17790Ala Glu His Pro Leu Leu Ala Ala Thr Val Gln Leu Ala Asp Thr Asp5855 586058655870ggc tgc cta ctg acg ggt cgc ctg tcc ttg cgc tcg cat ccg tgg ctg 17838Gly Cys Leu Leu Thr Gly Arg Leu Set Leu Arg Set His Pro Trp Leu587558805885ggc gat tac gag gtg ggg ggt gcg gtc ctg ctg tcg ggg tcg gcg ttc 17886Gly Asp Tyr Glu Val Gly Gly Ala Val Leu Leu Ser Gly Ser Ala Phe589058955900gtg gag ctg gcg gtc cag gtt ggc gaa cgc gtg ggc tgc acc cga atc 17934Val Glu Leu Ala Val Gln Val Gly Glu Arg Val Gly Cys Thr Arg Ile590559105915gag caa ctc act gtg cat gcg ccg ctg gtg gtt cct gtg ggt ggg ggt 17982Glu Gln Leu Thr Val His Ala Pro Leu Val Val Pro Val Gly Gly Gly592059255930gtg agt gtg cag gtt ggg gtt gcg gct gcg gat ggg gag ggg cgg cgt 18030Val Ser Val Gln Val Gly Val Ala Ala Ala Asp Gly Glu Gly Arg Arg5935 594059455950ttg gtg agt gtg tat gcg cgg ggt ggg agt gct tgt ggt ggg ggt ggt 18078Leu Val Ser Val Tyr Ala Arg Gly Gly Ser Ala Cys Gly Gly Gly Gly595559605965gcg tcg ggt ggg gtg tgg acg tgt cat gcc tcg ggg gtg ctg gtt gag 18126Ala Ser Gly Gly Val Trp Thr Cys His Ala Ser Gly Val Leu Val Glu597059755980gct gct gct ggt ggt ggt gtg gtg gtg gat ggt ctg gcg ggg gtg tgg 18174Ala Ala Ala Gly Gly Gly Val Val Val Asp Gly Leu Ala Gly Val Trp598559905995ccg ccg cgg ggt gcg gtg gcg gtg gat gtc gat ggt gtc cgt gac cgt 18222Pro Pro Arg Gly Ala Val Ala Val Asp Val Asp Gly Val Arg Asp Arg600060056010ttg gct ggg gct ggt tgt gtt ttg ggg ccg gtg ttt tcg ggg ctg cgt 18270Leu Ala Gly Ala Gly Cys Val Leu Gly Pro Val Phe Ser Gly Leu Arg6015 602060256030gcg gtg tgg cgt gat ggg ggg gat ttg ctg gct gag gtg tgt ctg ccg 18318Ala Val Trp Arg Asp Gly Gly Asp Leu Leu Ala Glu Val Cys Leu Pro603560406045gag gag gcg tgg ggt gat gcg gct ggt ttt ggg ctg cat ccg gcg ttg 18366Glu Glu Ala Trp Gly Asp Ala Ala Gly Phe Gly Leu His Pro Ala Leu605060556060ctg gat ggt gtg gtc cag ccg ttg tcg gtg ttg ctt ccg ggt ggg acg 18414Leu Asp Gly Val Val Gln Pro Leu Ser Val Leu Leu Pro Gly Gly Thr606560706075ggg ttt ggg gag ggg gcg ggg ttc ggg gag ggt gtt cgg gtg ccg gct 18462Gly Phe Gly Glu Gly Ala Gly Phe Gly Glu Gly Val Arg Val Pro Ala608060856090gtg tgg ggt ggt gtg tcg ctt cac cgg gcg ggt gtg acc ggt gtg cgg 18510Val Trp Gly Gly Val Ser Leu His Arg Ala Gly Val Thr Gly Val Arg6095 610061056110gtg cgt gtg tgg gct gta ggg cgg ggc ggc ggg cgt gag gcg gtg tcg 18558Val Arg Val Trp Ala Val Gly Arg Gly Gly Gly Arg Glu Ala Val Ser611561206125gtc gtg gtc ggg gat gag gcg ggt gtg ccg gtg gcg tcg gtc gat cgt 18606Val Val Val Gly Asp Glu Ala Gly Val Pro Val Ala Ser Val Asp Arg613061356140ctt gag ttg cgg cct gtg gat atg ggt cag ttg cgt gct gtc tcg gtt 18654Leu Glu Leu Arg Pro Val Asp Met Gly Gln Leu Arg Ala Val Ser Val614561506155tcg gcg ggg cgg cgg ggt tcg ctg tat gcg gtg cag tgg gct gag gtg 18702Ser Ala Gly Arg Arg Gly Ser Leu Tyr Ala Val Gln Trp Ala Glu Val616061656170ggt cct gtg ccg gtg tgt ggg cag gcg tgg gcg tgg cac gag gac gtg 18750Gly Pro Val Pro Val Cys Gly Gln Ala Trp Ala Trp His Glu Asp Val6175 618061856190ggt gag agc ggt ggt ggg cct gtg ccg ggg gtg gtg gtg ttg cgg tgc 18798Gly Glu Ser Gly Gly Gly Pro Val Pro Gly Val Val Val Leu Arg Cys619562006205ccg gat gcc ggt gcc ggt ggc ggc ggt ggc ggt ggt gtg ggt gag gtt 18846Pro Asp Ala Gly Ala Gly Gly Gly Gly Gly Gly Gly Val Gly Glu Val621062156220gtt ggt ggg gtg ttg ggt gtg gtg cag ggg tgg ctg ggg ctg gag cgg 18894Val Gly Gly Val Leu Gly Val Val Gln Gly Trp Leu Gly Leu Glu Arg622562306235ttt gcg ggt tcg cgg ctg gtg gtg gtg acc cgg ggt gcg gtg gtg gcc 18942Phe Ala Gly Ser Arg Leu Val Val Val Thr Arg Gly Ala Val Val Ala624062456250ggc caa gaa gac ggc ccg gtg gat gtg gtg ggt gcg gcg gtg tgg ggg 18990Gly Gln Glu Asp Gly Pro Val Asp Val Val Gly Ala Ala Val Trp Gly6255 626062656270ctg gtg cgg tcg gcg cag gct gag cat ccg gac cgg ttt gtc ctc ctc 19038Leu Val Arg Ser Ala Gln Ala Glu His Pro Asp Arg Phe Val Leu Leu627562806285gac ctc gac acc gac acc gac acc ggc acc gac ctc gac acc ggt gct 19086Asp Leu Asp Thr Asp Thr Asp Thr Gly Thr Asp Leu Asp Thr Gly Ala629062956300ggt gct ggt gct ggt gct ggt tgg ggc gtg gat ggt ggg cat gtg gcg 19134Gly Ala Gly Ala Gly Ala Gly Trp Gly Val Asp Gly Gly His Val Ala630563106315gcg gtg gtg gcg tgt ggt gag ccg cag ttg gcg gtg cgt ggt gag cgg 19182Ala Val Val Ala Cys Gly Glu Pro Gln Leu Ala Val Arg Gly Glu Arg632063256330gtg ctg gcc gca cgc ctg acg cga ctt gag tcg tcc gtt gat gta cct 19230Val Leu Ala Ala Arg Leu Thr Arg Leu Glu Ser Ser Val Asp Val Pro6335 634063456350gct cag cgg tcc ggt gat gtt gct ggt cgg gag gtg ttg ccg tgg ttg 19278Ala Gln Arg Ser Gly Asp Val Ala Gly Arg Glu Val Leu Pro Trp Leu635563606365tcg ggt ggg tcg gtg ttg gtg acg ggt ggg acg ggt gtg ctg ggt gcg 19326Ser Gly Gly Ser Val Leu Val Thr Gly Gly Thr Gly Val Leu Gly Ala637063756380gcg gtg gcg cgg cat ctg gct ggt gtg tgt ggg gtg cgg gat ctg ctg 19374Ala Val Ala Arg His Leu Ala Gly Val Cys Gly Val Arg Asp Leu Leu638563906395ttg gtg agc cgg cgt ggt ccg gat gct ccg ggt gcg gag ggt ttg cgg 19422Leu Val Ser Arg Arg Gly Pro Asp Ala Pro Gly Ala Glu Gly Leu Arg640064056410gcg gag ctg gcc gcg ttg ggg gcg gag gtg cgg att gtt gcg tgt gat 19470Ala Glu Leu Ala Ala Leu Gly Ala Glu Val Arg Ile Val Ala Cys Asp6415 642064256430gtg ggg gag cgg cgg gag gtg gtc cgg ctg ctg gag ggt gtt cct gcc 19518Val Gly Glu Arg Arg Glu Val Val Arg Leu Leu Glu Gly Val Pro Ala643564406445ggg tgt ccg ctg acg ggt gtc gtg cat gcg gct ggt gtg ctg gac gat 19566Gly Cys Pro Leu Thr Gly Val Val His Ala Ala Gly Val Leu Asp Asp645064556460gcg acg atc gcc tct ctc acg ccc gag cgg ctg ggc acg gtg ttc gcg 19614Ala Thr Ile Ala Ser Leu Thr Pro Glu Arg Leu Gly Thr Val Phe Ala646564706475gcc aag gtg gat gcc gct ctt ttg ctg gat gag ctg acg cgg ggt atg 19662Ala Lys Val Asp Ala Ala Leu Leu Leu Asp Glu Leu Thr Arg Gly Met648064856490gag ctg tcg gcg ttc gtg ctg ttc tcc tcg gcc gcg ggg atc ctg ggg 19710Glu Leu Ser Ala Phe Val Leu Phe Ser Ser Ala Ala Gly Ile Leu Gly6495 650065056510tcg gcc ggg cag ggc aac tac gcc gcg gcc aat gcc gct ctg gac gcg 19758Ser Ala Gly Gln Gly Asn Tyr Ala Ala Ala Asn Ala Ala Leu Asp Ala651565206525ctg gcg tac cgg cgg cgg gcg gcg ggt ctg ccg ggg gtg tcg ctg gcg 19806Leu Ala Tyr Arg Arg Arg Ala Ala Gly Leu Pro Gly Val Ser Leu Ala653065356540tgg ggg ctg tgg gaa gag gcc agc ggg atg acc ggg cac ctg gcc ggc 19854Trp Gly Leu Trp Glu Glu Ala Ser Gly Met Thr Gly His Leu Ala Gly654565506555acc gac cac cgg cgc atc atc cgt tcc ggt ctg cat ccc atg tcg acc 19902Thr Asp His Arg Arg Ile Ile Arg Ser Gly Leu His Pro Met Ser Thr656065656570ccg gac gca ctg gct ctc ttc gat gcg gcc ctg gct ctg gac cgg ccg 19950Pro Asp Ala Leu Ala Leu Phe Asp Ala Ala Leu Ala Leu Asp Arg Pro6575 658065856590gtc ctg ctg ccc gcc gac ctg cgt ccc gcc ccg ccc ctg ccg ccc ctg 19998Val Leu Leu Pro Ala Asp Leu Arg Pro Ala Pro Pro Leu Pro Pro Leu659566006605ctg cag gac ctc ctg ccc gcc acc cgc cgc cgc acc acc cgc acc acc 20046Leu Gln Asp Leu Leu Pro Ala Thr Arg Arg Arg Thr Thr Arg Thr Thr661066156620act acc ggt ggt gcg gac aac ggc gcc cag ctg cat gcc cgg ctg gcc 20094Thr Thr Gly Gly Ala Asp Asn Gly Ala Gln Leu His Ala Arg Leu Ala662566306635ggc cag aca cac gaa caa cag cac acc acc ctc ctc gcc ctg gtc cgc 20142Gly Gln Thr His Glu Gln Gln His Thr Thr Leu Leu Ala Leu Val Arg664066456650tcc cac atc gcc acc gtc ctc ggc cac acc acc ccc gac acc atc ccc 20190Ser His Ile Ala Thr Val Leu Gly His Thr Thr Pro Asp Thr Ile Pro6655 666066656670ccc gac cgc gcg ttc cgc gac ctc ggc ttc gac tcc ctc acc gcc gtc 20238Pro Asp Arg Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Thr Ala Val667566806685gaa cta cgc aac cgg ctc tcc cgc acc acc gga ctc cgc ctc ccc acc 20286Glu Leu Arg Asn Arg Leu Ser Arg Thr Thr Gly Leu Arg Leu Pro Thr669066956700acc ctc gcc ttc gac cac ccc aac ccc acc acc ctc acc cac cac ctc 20334Thr Leu Ala Phe Asp His Pro Asn Pro Thr Thr Leu Thr His His Leu670567106715cac aca caa ctt ctg ggc tcg gac agc act gcc tcc atc cca gct ccc 20382His Thr Gln Leu Leu Gly Ser Asp Ser Thr Ala Ser Ile Pro Ala Pro672067256730cgt gct gcg gct gtg cct gca gac cag gac gag ccc gtc gcg atc att 20430Arg Ala Ala Ala Val Pro Ala Asp Gln Asp Glu Pro Val Ala Ile Ile6735 674067456750ggc atg gcg tgc cgc tat ccc gga ggc gtc acc tca gcc gag gag ctg 20478Gly Met Ala Cys Arg Tyr Pro Gly Gly Val Thr Ser Ala Glu Glu Leu675567606765tgg gaa ctg ctc gca tcg ggg agg gac acg gtc ggc gag ttt ccg acg 20526Trp Glu Leu Leu Ala Ser Gly Arg Asp Thr Val Gly Glu Phe Pro Thr677067756780gac cgt ggg tgg gac ctg gaa gca ctg ttc gat ccg gaa ccg ggt cgg 20574Asp Arg Gly Trp Asp Leu Glu Ala Leu Phe Asp Pro Glu Pro Gly Arg678567906795ccg ggc acc tcg tac acc cgc tgt ggg agt ttc ctc tac gac gcg ggg 20622Pro Gly Thr Ser Tyr Thr Arg Cys Gly Ser Phe Leu Tyr Asp Ala Gly680068056810gag ttc gac gcc ggc ttc ttc ggg atc agt ccg cgt gag gca ctg gcg 20670Glu Phe Asp Ala Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala6815 682068256830atg gac ccg cag cag cga ttg ctg ctg gag gcc tca tgg gag gcc atg 20718Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Ala Ser Trp Glu Ala Met683568406845gag cag gca ggt att gac cct acg acc gta cgc ggg agc cag aca ggc 20766Glu Gln Ala Gly Ile Asp Pro Thr Thr Val Arg Gly Ser Gln Thr Gly685068556860gtg ttc gcg ggc ctc att ccg cag gcc tat gga ccc agg ctg cac gaa 20814Val Phe Ala Gly Leu Ile Pro Gln Ala Tyr Gly Pro Arg Leu His Glu686568706875aac gcc gca gcc gac acc gag ggc tat gtc ctg acc ggc aca tcc ggg 20862Asn Ala Ala Ala Asp Thr Glu Gly Tyr Val Leu Thr Gly Thr Ser Gly688068856890agt gtg gcc tcc ggt cgt atc tcg tac acg ttt ggt ttt gag ggt cct 20910Ser Val Ala Ser Gly Arg Ile Ser Tyr Thr Phe Gly Phe Glu Gly Pro6895 690069056910gcg gtg tcg gtg gac acg gct tgt tcc tcg tcg ttg gtg gct tta cat 20958Ala Val Ser Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His691569206925ctg gcc tgt cag gcg ttg cgt gcg ggt gag tgc tcg atg gcg ctt gcc 21006Leu Ala Cys Gln Ala Leu Arg Ala Gly Glu Cys Ser Met Ala Leu Ala693069356940ggg ggt gtg acg gtg atg tcg tct ccg ggt gcc ttc gtg gag ttt tcg 21054Gly Gly Val Thr Val Met Ser Ser Pro Gly Ala Phe Val Glu Phe Ser694569506955cgg cag cgg ggt ctg gcc gcg gac ggg cat tgc aag gcg ttc tcg gcg 21102Arg Gln Arg Gly Leu Ala Ala Asp Gly His Cys Lys Ala Phe Ser Ala696069656970gcg gcg gac ggg acc ggc tgg ggt gag ggt gtg ggg atg ctg ctg gtg 21150Ala Ala Asp Gly Thr Gly Trp Gly Glu Gly Val Gly Met Leu Leu Val6975 698069856990gag cgg ctc tcc gac gcc cgt cgc aac ggt cac cgt gtc ctg gcc gtg 21198Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly His Arg Val Leu Ala Val699570007005gtg cgt ggc agt gcg gtc aac cag gac ggt gcg agc aac ggg ctg acc 21246Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr701070157020gcg ccc aac ggg ccc tcc cag cag cgt gtc atc cgc cag gcc ctc gcc 21294Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala702570307035aac gcc ggc ttg tcg gcc ggt gat gtc gat gcg gtg gag gcc cac ggc 21342Asn Ala Gly Leu Ser Ala Gly Asp Val Asp Ala Val Glu Ala His Gly704070457050acc ggc acc act ttg ggc gac ccg atc gag gcc cag gcc ctc ctt gcg 21390Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala7055 706070657070acc tac ggg cag gac cgt gcc ggc gag ggg ccg ctg tgg ctg ggc tcg 21438Thr Tyr Gly Gln Asp Arg Ala Gly Glu Gly Pro Leu Trp Leu Gly Ser707570807085gtc aag tcc aat gtc ggt cac aca cag gct gcc gcg ggc gtc gcc ggg 21486Val Lys Ser Asn Val Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly709070957100gtg atc aag atg gtg atg gcg ctg cgg aat ggt ctg ctg ccg cgg acg 21534Val Ile Lys Met Val Met Ala Leu Arg Asn Gly Leu Leu Pro Arg Thr710571107115ttg cat gtg gat gag ccg tcg ccg cat gtg gac tgg tcc gcg ggt gcg 21582Leu His Val Asp Glu Pro Ser Pro His Val Asp Trp Ser Ala Gly Ala712071257130gtg cag ctg ctg acg gag acg gtg ccc tgg ccc ggc ggg gag ggg cgg 21630Val Gln Leu Leu Thr Glu Thr Val Pro Trp Pro Gly Gly Glu Gly Arg7135 714071457150cta cgg cgg gca gga gtg tca tca ttc ggc gtc agc ggc acc aac gcc 21678Leu Arg Arg Ala Gly Val Ser Ser Phe Gly Val Ser Gly Thr Asn Ala715571607165cac gtc atc ctc gaa gaa gca ccc gcc cac aac atc ccg tca gac aca 21726His Val Ile Leu Glu Glu Ala Pro Ala His Asn Ile Pro Ser Asp Thr717071757180ccc gcc gac gac gtt ccg ggg gga cca ccc gcc ggc gag gat gcc ggt 21774Pro Ala Asp Asp Val Pro Gly Gly Pro Pro Ala Gly Glu Asp Ala Gly718571907195agt ggc gag gag gct gct gcc ggc agt cca ggg gtg tgg ccg tgg ctg 21822Ser Gly Glu Glu Ala Ala Ala Gly Ser Pro Gly Val Trp Pro Trp Leu720072057210gtg tcg gcc aag tcg cag ccg gcc ctg cgc gcc cag gcc cag gcc ctg 21870Val Ser Ala Lys Ser Gln Pro Ala Leu Arg Ala Gln Ala Gln Ala Leu7215 722072257230cac gcc cac ctc acc gac cac ccc ggc ctc gac ctc gcc gac gtc gga 21918His Ala His Leu Thr Asp His Pro Gly Leu Asp Leu Ala Asp Val Gly723572407245tac acc ctc gcc cac gcc cgc gcc gtg ttc gac cac cgc gcc acc ctc 21966Tyr Thr Leu Ala His Ala Arg Ala Val Phe Asp His Arg Ala Thr Leu725072557260atc gcc gcc gac cgc gac acc ttc ctg caa gca ctc cag gca ctc gcc 22014Ile Ala Ala Asp Arg Asp Thr Phe Leu Gln Ala Leu Gln Ala Leu Ala726572707275gca ggc gaa ccc cac ccc gcc gtc atc cac agc agc gcc cca ggc ggg 22062Ala Gly Glu Pro His Pro Ala Val Ile His Ser Ser Ala Pro Gly Gly728072857290acc ggg acc ggg gag gcc gca gga aag acc gca ttc atc tgc tcc gga 22110Thr Gly Thr Gly Glu Ala Ala Gly Lys Thr Ala Phe Ile Cys Ser Gly7295 730073057310cag ggc acc caa cgc ccc ggc atg gcc cac ggc ctc tac cac acc cac 22158Gln Gly Thr gln Arg Pro Gly Met Ala His Gly Leu Tyr His Thr His731573207325ccc gtc ttc gcc gcc gca ctc aac gac atc tgc acc cac ctc gac ccc 22206Pro Val Phe Ala Ala Ala Leu Asn Asp Ile Cys Thr His Leu Asp Pro733073357340cac ctc gac cac ccc ctc ctc ccc ctc ctc acc cag gac ccc aac acc 22254His Leu Asp His Pro Leu Leu Pro Leu Leu Thr Gln Asp Pro Asn Thr734573507355cag gac acc acc acc ctc gaa gaa gcg gcc gca ctg ctc cag cag acc 22302Gln Asp Thr Thr Thr Leu Glu Glu Ala Ala Ala Leu Leu Gln Gln Thr736073657370ccg tac gcc cag ccc gcc ctc ttc gcc ttc cag gtc gcc ctc cac cgc 22350Pro Tyr Ala Gln Pro Ala Leu Phe Ala Phe Gln Val Ala Leu His Arg7375 738073857390ctc ctc acc gac ggc tac cac atc acc ccc cac tac tac gcc gga cac 22398Leu Leu Thr Asp Gly Tyr His Ile Thr Pro His Tyr Tyr Ala Gly His739574007405tcc ctc ggc gaa atc acc gcc gcc cac ctc gcc ggc atc ctc acc ctc 22446Ser Leu Gly Glu Ile Thr Ala Ala His Leu Ala Gly Ile Leu Thr Leu741074157420acc gac gcc acc acc ctc atc acc caa cgc gcc acc ctc atg caa acc 22494Thr Asp Ala Thr Thr Leu Ile Thr Gln Arg Ala Thr Leu Met Gln Thr742574307435atg ccc ccc ggc acc atg acc acc ctc cac acc acc ccc cac cac atc 22542Met Pro Pro Gly Thr Met Thr Thr Leu His Thr Thr Pro His His Ile744074457450acc cac cac atc acc gcc cac gaa aac gac ctc gcc atc gcc gcc atc 22590Thr His His Ile Thr Ala His Glu Asn Asp Leu Ala Ile Ala Ala Ile7455 746074657470aac acc ccc acc tcc ctc gtc atc agc ggc acc ccc cac acc gtc caa 22638Asn Thr Pro Thr Ser Leu Val Ile Ser Gly Thr Pro His Thr Val Gln747574807485cac atc acc acc ctc tgc caa caa caa ggc atc aaa acc aaa acc ctc 22686His Ile Thr Thr Leu Cys Gln Gln Gln Gly Ile Lys Thr Lys Thr Leu749074957500ccc acc aac cac gcc ttc cac tcc ccc cac acc aac ccc atc ctc aac 22734Pro Thr Asn His Ala Phe His Ser Pro His Thr Asn Pro Ile Leu Asn750575107515caa ctc cac cag cac acc caa acc ctc acc tac cac cca ccc cac acc 22782Gln Leu His Gln His Thr Gln Thr Leu Thr Tyr His Pro Pro His Thr752075257530ccc ctc atc acc gcc aac acc cca ccc gac caa ctc ctc acc ccc cac 22830Pro Leu Ile Thr Ala Asn Thr Pro Pro Asp Gln Leu Leu Thr Pro His7535 754075457550tac tgg acc caa caa gcc cgc aac acc gtc gac ata gcc acc acc acc 22878Tyr Trp Thr Gln Gln Ala Arg Asn Thr Val Asp Ile Ala Thr Thr Thr755575607565caa acc ctc cac caa cac ggc gtc acc acc tac atc gaa ctc gga ccc 22926Gln Thr Leu His Gln His Gly Val Thr Thr Tyr Ile Glu Leu Gly Pro757075757580gac aac acc ctc acc acc ctc acc cac cac aac ctc ccc aac acc ccc 22974Asp Asn Thr Leu Thr Thr Leu Thr His His Asn Leu Pro Asn Thr Pro758575907595acc acc acc ctc acc ctc acc cac ccc cac cac cac ccc caa acc cac 23022Thr Thr Thr Leu Thr Leu Thr His Pro His His His Pro Gln Thr His760076057610ctc ctc acc aac ctc gcc aaa acc acc acc acc tgg cac ccc cac cac 23070Leu Leu Thr Asn Leu Ala Lys Thr Thr Thr Thr Trp His Pro His His7615 762076257630tac acc cac cac cac aac caa ccc cac acc cac acc cac ctc gac ctc 23118Tyr Thr His His His Asn Gln Pro His Thr His Thr His Leu Asp Leu763576407645ccc acc tac ccc ttc caa cac cac cac tac tgg ctc gaa agc aca cag 23166Pro Thr Tyr Pro Phe Gln His His His Tyr Trp Leu Glu Ser Thr Gln765076557660ccc ggt gcc ggc aac gtg tca gca gcc gga ctc gac ccc acc gaa cac 23214Pro Gly Ala Gly Asn Val Ser Ala Ala Gly Leu Asp Pro Thr Glu His766576707675ccc cta ctc ggc gcc aca ttg gaa ctg gcc gaa ggg gac ggc tgc cta 23262Pro Leu Leu Gly Ala Thr Leu Glu Leu Ala Glu Gly Asp Gly Cys Leu768076857690ctg acg ggg cgc ctc tcg ttg cgc acg cat ccc tgg ctc gcc ggc cat 23310Leu Thr Gly Arg Leu Ser Leu Arg Thr His Pro Trp Leu Ala Gly His7695 770077057710gcg gta ggc ggt gtc gtg ctg ctg ccg ggt acg gcc ttc gcg gaa ctg 23358Ala Val Gly Gly Val Val Leu Leu Pro Gly Thr Ala Phe Ala Glu Leu771577207725gcc ctt cat gcc gga gaa agt gtg ggt tgc gac cac gtg gac gag ctg 23406Ala Leu His Ala Gly Glu Ser Val Gly Cys Asp His Val Asp Glu Leu773077357740acg ctc cac aca ccg ttg gtc att cct gag gtc gga gac gtg acc ctt 23454Thr Leu His Thr Pro Leu Val Ile Pro Glu Val Gly Asp Val Thr Leu774577507755cag gtt gcc att gcg gcg ccg gac gag tcg ggt cgc cgc atg atg acc 23502Gln Val Ala Ile Ala Ala Pro Asp Glu Ser Gly Arg Arg Met Met Thr776077657770atc cac tca cgc ggt gag ggc ggc agt ggt gga gcc gat gcg tcg gcc 23550Ile His Ser Arg Gly Glu Gly Gly Ser Gly Gly Ala Asp Ala Ser Ala7775 778077857790agt gcg tgg acg cgt cat gcc gcg ggt gtg ctg agc cct gcc aag gac 23598Ser Ala Trp Thr Arg His Ala Ala Gly Val Leu Ser Pro Ala Lys Asp779578007805gat gac act gcc tcg tac gag ctg ctt gcg gga ccc tgg cct ccc gtt 23646Asp Asp Thr Ala Ser Tyr Glu Leu Leu Ala Gly Pro Trp Pro Pro Val781078157820gga gct acg cct gtc gac ctg aac acg gct tac gat caa atg gcc gac 23694Gly Ala Thr Pro Val Asp Leu Asn Thr Ala Tyr Asp Gln Met Ala Asp782578307835gcc ggc ttt gct tat ggc ctg gca ttc caa ggg ttg cgc gcg gcc tgg 23742Ala Gly Phe Ala Tyr Gly Leu Ala Phe Gln Gly Leu Arg Ala Ala Trp784078457850cgc tac ggc gac gac atc ctc gtc gag gca cgt ctt ccc gaa gaa gtg 23790Arg Tyr Gly Asp Asp Ile Leu Val Glu Ala Arg Leu Pro Glu Glu Val7855 786078657870tcg gga gac gcg gcg gcg tac ggt ctg cac ccg gcc ctg ctc gac gct 23838Ser Gly Asp Ala Ala Ala Tyr Gly Leu His Pro Ala Leu Leu Asp Ala787578807885gcc ctt cag ggc acc ggc ctg ctt tct gtg gcg ggt ccg ggg acg ccc 23886Ala Leu Gln Gly Thr Gly Leu Leu Ser Val Ala Gly Pro Gly Thr Pro789078957900gtc gtg ccc cat gtg tgg aac ggt ctg cgg ttc cgt acg cat ggt gca 23934Val Val Pro His Val Trp Asn Gly Leu Arg Phe Arg Thr His Gly Ala790579107915gtc tcc gtg cgc gcg tgc ctg tcg acg ctt gga gcg aca ggg gcg gcc 23982Val Ser Val Arg Ala Cys Leu Ser Thr Leu Gly Ala Thr Gly Ala Ala792079257930gtg tgc gtg cgc atc acc gac gac acc ggg gtg ccg gtg gcg tcg gtc 24030Val Cys Val Arg lle Thr Asp Asp Thr Gly Val Pro Val Ala Ser Val7935 794079457950gat cgt ctt gag ttg cgg cct gtg gat atg ggt cag ttg cgt gct gtc 24078Asp Arg Leu Glu Leu Arg Pro Val Asp Met Gly Gln Leu Arg Ala Val795579607965tcg gtt tcg gcg ggg cgg cgg ggt tcg ctg tat gcg gtg cag tgg gct 24126Ser Val Ser Ala Gly Arg Arg Gly Ser Leu Tyr Ala Val Gln Trp Ala797079757980gag gtg ggt cct gtg ccg gtg tgt ggg cag gcg tgg gcg tgg cac gag 24174Glu Val Gly Pro Val Pro Val Cys Gly Gln Ala Trp Ala Trp His Glu798579907995gac gtg ggt gag agc ggt ggt ggg cct gtg ccg ggg gtg gtg gtg ttg 24222Asp Val Gly Glu Ser Gly Gly Gly Pro Val Pro Gly Val Val Val Leu800080058010cgg tgc ccg gat gcc ggt gcc gat ggc ggc ggt ggc ggt ggt gtg ggt 24270Arg Cys Pro Asp Ala Gly Ala Asp Gly Gly Gly Gly Gly Gly Val Gly8015 802080258030gag gtt gtt ggt ggg gtg ttg ggt gtg gtg cag ggg tgg ctg ggg ctg 24318Glu Val Val Gly Gly Val Leu Gly Val Val Gln Gly Trp Leu Gly Leu803580408045gag cgg ttt gcg ggt tcg cgg ctg gtg gtg gtg acc cgg ggt gcg gtg 24366Glu Arg Phe Ala Gly Ser Arg Leu Val Val Val Thr Arg Gly Ala Val805080558060gtg gcc ggc ccg gag gac ggc ccg gtg gat gtg gtg ggt gcg gcg gtg 24414Val Ala Gly Pro Glu Asp Gly Pro Val Asp Val Val Gly Ala Ala Val806580708075tgg ggg ctg gtg cgg tcg gcg cag gct gag cat ccg gac cgg ttt gtc 24462Trp Gly Leu Val Arg Ser Ala Gln Ala Glu His Pro Asp Arg Phe Val808080858090ctc ctc gac ctg gac acc gac ctc gac agc ggc gct gac gcc gat gcc 24510Leu Leu Asp Leu Asp Thr Asp Leu Asp Ser Gly Ala Asp Ala Asp Ala8095 810081058110ggc aac gag gcc ggt atg ggg tct ggt ctg gat ggt ggg cgt gtg gct 24558Gly Asn Glu Ala Gly Met Gly Ser Gly Leu Asp Gly Gly Arg Val Ala811581208125gcg gtg gtg gcg tgt ggt gag ccg cag ttg gcg gtg cgt ggt gag cgg 24606Ala Val Val Ala Cys Gly Glu Pro Gln Leu Ala Val Arg Gly Glu Arg813081358140gtg ctg gcc gca cgc ctg aca cga ctt gag tcg ccg gtt gat gta tcg 24654Val Leu Ala Ala Arg Leu Thr Arg Leu Glu Ser Pro Val Asp Val Ser814581508155ggt cgg gag gtg ttg ccg tgg ttg tcg ggt ggg tcg gtg ttg gtg acg 24702Gly Arg Glu Val Leu Pro Trp Leu Ser Gly Gly Ser Val Leu Val Thr816081658170ggt ggg acg ggt gtg ctg ggt gcg gcg gtg gcg cgg cat ctg gct ggt 24750Gly Gly Thr Gly Val Leu Gly Ala Ala Val Ala Arg His Leu Ala Gly8175 818081858190gtg tgt ggg gtg cgg gat ctg ttg ttg gtg agc cgg cgt ggt ccg gat 24798Val Cys Gly Val Arg Asp Leu Leu Leu Val Ser Arg Arg Gly Pro Asp819582008205gct ccg ggt gcg gag ggt ttg cgg gcg gag ctg gcc gcg ttg ggg gcg 24846Ala Pro Gly Ala Glu Gly Leu Arg Ala Glu Leu Ala Ala Leu Gly Ala821082158220gag gtg cgg att gtt gcg tgt gat gtg ggg gag cgg cgg gag gtg gtc 24894Glu Val Arg Ile Val Ala Cys Asp Val Gly Glu Arg Arg Glu Val Val822582308235cgg ctg ctg gag ggt gtt cct gcc ggg tgt ccg ctg acg ggt gtc gtg 24942Arg Leu Leu Glu Gly Val Pro Ala Gly Cys Pro Leu Thr Gly Val Val824082458250cat gcg gct ggt gtg ctg gac gat gcg acg atc gcc tct ctc acg ccc 24990His Ala Ala Gly Val Leu Asp Asp Ala Thr Ile Ala Ser Leu Thr Pro8255 826082658270gag cgg ctg ggc acg gtg ttc gcg gcc aag gtg gat gcc gct ctt ttg 25038Glu Arg Leu Gly Thr Val Phe Ala Ala Lys Val Asp Ala Ala Leu Leu827582808285ctg gat gag ctg acg cgg ggt atg gag ctg tcg gcg ttc gtg ctg ttc 25086Leu Asp Glu Leu Thr Arg Gly Met Glu Leu Ser Ala Phe Val Leu Phe829082958300tcc tcg gcc gcg ggg atc ctg ggg tcg gcc ggg cag ggc aac tac gcc 25134Ser Ser Ala Ala Gly Ile Leu Gly Ser Ala Gly Gln Gly Asn Tyr Ala830583108315gcg gcc aat gcc gct ctg gac gcg ctg gcg tac cgg cgg cgg gcg gcg 25182Ala Ala Asn Ala Ala Leu Asp Ala Leu Ala Tyr Arg Arg Arg Ala Ala832083258330ggt ctg ccg ggg gtg tcg ctg gcg tgg ggg ctg tgg gaa gag gcc agc 25230Gly Leu Pro Gly Val Ser Leu Ala Trp Gly Leu Trp Glu Glu Ala Ser8335 834083458350ggg atg acc ggg cac ctg gcc ggc acc gac cac cgg cgc atc atc cgt 25278Gly Met Thr Gly His Leu Ala Gly Thr Asp His Arg Arg Ile Ile Arg835583608365tcc ggt ctg cat ccc atg tcg acc ccg gac gca ctg gct ctc ttc gat 25326Ser Gly Leu His Pro Met Ser Thr Pro Asp Ala Leu Ala Leu Phe Asp837083758380gcg gcc ctg gct ctg gac cgg ccg gtc ctg ctg ccc gcc gac ctg cgt 25374Ala Ala Leu Ala Leu Asp Arg Pro Val Leu Leu Pro Ala Asp Leu Arg838583908395ccc gcc ccg ccc ctg ccg ccc ctg ctg cag gac ctc ctg ccc gcc acc 25422Pro Ala Pro Pro Leu Pro Pro Leu Leu Gln Asp Leu Leu Pro Ala Thr840084058410cgc cgc cgc acc acc cgc acc acc act acc ggt ggt gcg gac aac ggc 25470Arg Arg Arg Thr Thr Arg Thr Thr Thr Thr Gly Gly Ala Asp Asn Gly8415 842084258430gcc cag ctg cat gcc cgg ctg gcc ggc cag aca cac gaa caa cag cac 25518Ala Gln Leu His Ala Arg Leu Ala Gly Gln Thr His Glu Gln Gln His843584408445acc acc ctc ctc gcc ctg gtc cgc tcc cac atc gcc acc gtc ctc ggc 25566Thr Thr Leu Leu Ala Leu Val Arg Ser His Ile Ala Thr Val Leu Gly845084558460cac aac gcg ccg gag atg atc ccc gtt gac tcg gcg ttc cgc gac cta 25614His Asn Ala Pro Glu Met Ile Pro Val Asp Ser Ala Phe Arg Asp Leu846584708475ggc ttc gac tcc ttg aca gcg gtg gaa ctc cgt aac cgc ctg ggt gag 25662Gly Phe Asp Ser Leu Thr Ala Val Glu Leu Arg Asn Arg Leu Gly Glu8480 8485 8490gca acg gga ctg cga ctg ccg acc agt ctg gtc ttc gac cag ccg aat 25710Ala Thr Gly Leu Arg Leu Pro Thr Ser Leu Val Phe Asp Gln Pro Asn8495 850085058510gca gcg acc ctg gcg cgt cac cta cgt cgt gag ctg atg ggc gac gac 25758Ala Ala Thr Leu Ala Arg His Leu Arg Arg Glu Leu Met Gly Asp Asp851585208525gcg gaa ggc gag acg cca tcg cag gtc gca ctt cat cag gtt gcc gcg 25806Ala Glu Gly Glu Thr Pro Ser Gln Val Ala Leu His Gln Val Ala Ala853085358540gat gag ccg att gcg att gtg ggg atg gcg tgt cgt ttt ccg ggt ggg 25854Asp Glu Pro Ile Ala Ile Val Gly Met Ala Cys Arg Phe Pro Gly Gly854585508555gtg tgt tcg ccg gag gag ttg tgg gag ctg gtt gcg tcg ggt ggg gat 25902Val Cys Ser Pro Glu Glu Leu Trp Glu Leu Val Ala Ser Gly Gly Asp856085658570gcg att ggt gaa ttt ccg gcc ggt cgg ggg tgg gat ctg gag ggg ttg 25950Ala Ile Gly Glu Phe Pro Ala Gly Arg Gly Trp Asp Leu Glu Gly Leu8575 858085858590ttt gat tcg gac cct gac cgg tcg ggg acg tcg tac gcg cgg tat ggc 25998Phe Asp Ser Asp Pro Asp Arg Ser Gly Thr Ser Tyr Ala Arg Tyr Gly859586008605ggg ttt ttg tat gag gcg ggg gag ttc gat gcg gac ttc ttc ggg atc 26046Gly Phe Leu Tyr Glu Ala Gly Glu Phe Asp Ala Asp Phe Phe Gly Ile861086158620agt ccg cgt gag gcg ttg gcg atg gat ccg cag cag cgg ttg ttg ctg 26094Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu862586308635gag acg tcg tgg gag gcg ttc gag cgg gcg ggt atc gat ccg ctg tcg 26142Glu Thr Ser Trp Glu Ala Phe Glu Arg Ala Gly Ile Asp Pro Leu Ser864086458650atg cgt ggc tcc cgt acg ggt gtc ttc gcc ggg gtg atg tac cac gac 26190Met Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Val Met Tyr His Asp8655 866086658670tac gcc gcg cgt ctc cac cat gtc ccc gag ggt ttc gaa ggc ctc atc 26238Tyr Ala Ala Arg Leu His His Val Pro Glu Gly Phe Glu Gly Leu Ile867586808685gcc aac ggc agc gca ggc agc gtc gcg acc ggc cgg gtg gcc tac agc 26286Ala Asn Gly Ser Ala Gly Ser Val Ala Thr Gly Arg Val Ala Tyr Ser869086958700ttt ggc ctt gag ggt ccg gcc gtg acc gtc gat acg gcg tgt tcg tcg 26334Phe Gly Leu Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser870587108715tcg ttg gtg gcg ttg cat tgg gcg gcg cag gcg ttg cgt gcg ggt gag 26382Ser Leu Val Ala Leu His Trp Ala Ala Gln Ala Leu Arg Ala Gly Glu872087258730tgt tcg atg gcg ctt gcc ggg ggt gtg acg gtg atg tcg tct ccg ggt 26430Cys Ser Met Ala Leu Ala Gly Gly Val Thr Val Met Ser Ser Pro Gly8735 874087458750acg ttt gtg gag ttc tca cgt cag cgg ggt ctg gcc gcg gac ggg cgg 26478Thr Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Ala Asp Gly Arg875587608765tgc aag gcc tat tcg gcg gct gct gac ggt acc ggc tgg gcc gag ggt 26526Cys Lys Ala Tyr Ser Ala Ala Ala Asp Gly Thr Gly Trp Ala Glu Gly877087758780gtg ggg atg ctg ctg gtg gag cgg ctc tcc gac gcc cgt cgc aac ggt 26574Val Gly Met Leu Leu Val Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly878587908795cac cgt gtc ctg gcc gtg gtg cgt ggc agt gcg gtc aac cag gac ggt 26622His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly880088058810gcg agc aac ggt ctg acc gcg ccc aac ggg ccc tcc cag cag cgt gtc 26670Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val8815 882088258830atc cgt cag gcc ctg gcc aat gcg gga ctg acc ccg gcc gat gtc gac 26718Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Thr Pro Ala Asp Val Asp883588408845gca gtg gag ggc cac ggc acc ggg acc act ctg ggg gac ccg atc gag 26766Ala Val Glu Gly His Gly Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu885088558860gcc cag gca ctc ctg gcc gcc tac gga caa cac cgc ccc cac cac cgc 26814Ala Gln Ala Leu Leu Ala Ala Tyr Gly Gln His Arg Pro His His Arg886588708875ccc ttg tgg ctg gga tcc ctc aaa tcc aac atc ggg cac gca cag gcc 26862Pro Leu Trp Leu Gly Ser Leu Lys Ser Asn Ile Gly His Ala Gln Ala888088858890gcc gcg ggc gtg ggc gga gtc atc aag atg gtg atg gcc ctg cgc aac 26910Ala Ala Gly Val Gly Gly Val Ile Lys Met Val Met Ala Leu Arg Asn8895 890089058910ggg ctg ctg cca cag acc ctc cac gtg gac gag ccc acc ccc cag gtc 26958Gly Leu Leu Pro Gln Thr Leu His Val Asp Glu Pro Thr Pro Gln Val891589208925gac tgg tcc aca ggc gca gta caa ctc ctg aca caa ccg gtg ccc tgg 27006Asp Trp Ser Thr Gly Ala Val Gln Leu Leu Thr Gln Pro Val Pro Trp893089358940ccc gcc gac ccg gcc ggc cgg cca cgc cac gcc ggc gtg tca tca ttc 27054Pro Ala Asp Pro Ala Gly Arg Pro Arg His Ala Gly Val Ser Ser Phe894589508955ggc gtc agc ggc acc aac gcc cat gtg att ttg gag gag gcg cct gcg 27102Gly Val Ser Gly Thr Asn Ala His Val Ile Leu Glu Glu Ala Pro Ala896089658970gcg gcg ggc ggt gct gcc ggt ggt ggg gtg tcg gtg ggt gct ccg aat 27150Ala Ala Gly Gly Ala Ala Gly Gly Gly Val Ser Val Gly Ala Pro Asn8975 898089858990cca gcc ctt ccg gtg gct gag tct gag ccg gtg ccg gtg ccg gtg ccg 27198Pro Ala Leu Pro Val Ala Glu Ser Glu Pro Val Pro Val Pro Val Pro899590009005gtg tcg gcg agg tct gag gcc ggg ttg cgg gcg cag gca cag gcg ttg 27246Val Ser Ala Arg Ser Glu Ala Gly Leu Arg Ala Gln Ala Gln Ala Leu901090159020cgc cag tac gtg gca gcc cgc ccg gac atg tca cct gcc gac atc ggt 27294Arg Gln Tyr Val Ala Ala Arg Pro Asp Met Ser Pro Ala Asp Ile Gly902590309035gcg ggt ctg gcc cgc ggc cgg gcc gta ctg gaa cac cgc gcc gtc atc 27342Ala Gly Leu Ala Arg Gly Arg Ala Val Leu Glu His Arg Ala Val Ile904090459050ctg gcc gcg gac cgc gag gaa ctg gcg cag gca ctg aca gcc ctg gca 27390Leu Ala Ala Asp Arg Glu Glu Leu Ala Gln Ala Leu Thr Ala Leu Ala9055 906090659070gcc ggc gaa ccc cac ccc cac atc acc aca ggc cac acc cgg ggc agt 27438Ala Gly Glu Pro His Pro His Ile Thr Thr Gly His Thr Arg Gly Ser907590809085gac cgc ggc ggc gtc gtc ttc gtc ttc ccc gga cag ggc ggc cag tgg 27486Asp Arg Gly Gly Val Val Phe Val Phe Pro Gly Gln Gly Gly Gln Trp909090959100gcc ggg atg ggc ctg acc ctg ctc acc tcc tca ccc gtg ttc gcc gaa 27534Ala Gly Met Gly Leu Thr Leu Leu Thr Ser Ser Pro Val Phe Ala Glu910591109115cac atc gac gca tgc gag aaa gcc ctc acc ccc tgg gtg ccc tgg tcc 27582His Ile Asp Ala Cys Glu Lys Ala Leu Thr Pro Trp Val Pro Trp Ser912091259130ctg acc gac atc ctg cac cgc gac ccc gac gac ccc gca tgg caa caa 27630Leu Thr Asp Ile Leu His Arg Asp Pro Asp Asp Pro Ala Trp Gln Gln9135 914091459150gcc gac gtg gtc cag ccc gtg ctc ttc agc atc atg gtc tcc ctc gcc 27678Ala Asp Val Val Gln Pro Val Leu Phe Ser Ile Met Val Ser Leu Ala915591609165gcc ctg tgg cgc tcc tac ggc atc gaa ccc gac gcg gtc ctc ggc cac 27726Ala Leu Trp Arg Ser Tyr Gly Ile Glu Pro Asp Ala Val Leu Gly His917091759180tcc cag gga gaa atc gcc gcc gcc cac atc tgc ggc gca ctc agc ctg 27774Ser Gln Gly Glu Ile Ala Ala Ala His Ile Cys Gly Ala Leu Ser Leu918591909195aaa gac gcc gcc aaa acc gtt gca ctg cgc agc cag gca ctg gcc gcc 27822Lys Asp Ala Ala Lys Thr Val Ala Leu Arg Ser Gln Ala Leu Ala Ala920092059210gta cga ggc cgg ggc gcc atg gtc tca ctg ccc ctg ccc gcc cag gac 27870Val Arg Gly Arg Gly Ala Met Val Ser Leu Pro Leu Pro Ala Gln Asp9215 922092259230gtg cag cag ctc att tcc gaa cgg tgg gaa ggg cag ttg tgg gtg gca 27918Val Gln Gln Leu Ile Ser Glu Arg Trp Glu Gly Gln Leu Trp Val Ala923592409245gcc ctc aac ggc ccc cac tcc acc acc gtc tcc ggc gac acc acc gca 27966Ala Leu Asn Gly Pro His Ser Thr Thr Val Ser Gly Asp Thr Thr Ala925092559260gta gaa gaa ctc ctc acc cac tgt gcc gac acc ggc cta cgg gcc aaa 28014Val Glu Glu Leu Leu Thr His Cys Ala Asp Thr Gly Leu Arg Ala Lys926592709275cgc atc ccc gtc gac tac gcc tcc cac tgc ccc cac gtc caa ccc ctc 28062Arg Ile Pro Val Asp Tyr Ala Ser His Cys Pro His Val Gln Pro Leu928092859290cac gac gaa ctc ctg cac ctg ctg gga gac atc acc ccc cag ccg tcc 28110His Asp Glu Leu Leu His Leu Leu Gly Asp Ile Thr Pro Gln Pro Ser9295 930093059310acc atg ccg ttc ttc tcc acc gtc gta ggg cac ctg gtc tgg tac acc 28158Thr Met Pro Phe Phe Ser Thr Val Val Gly His Leu Val Trp Tyr Thr931593209325aca acc ctg gac gcc gcc tac tgg tac cgc aac ctc cac cag ccc gtc 28206Thr Thr Leu Asp Ala Ala Tyr Trp Tyr Arg Asn Leu His Gln Pro Val933093359340cgc ttc agc cac gcc atc cag acc ctg acc gac gac gga cac cgc ccc 28254Arg Phe Ser His Ala Ile Gln Thr Leu Thr Asp Asp Gly His Arg Pro934593509355ttc atc gaa atc agt ccc cac ccc acc ctc gtc ccc gcc atc gaa gac 28302Phe Ile Glu Ile Ser Pro His Pro Thr Leu Val Pro Ala Ile Glu Asp936093659370acc acc gaa aac acc acc gaa aac atc acc gcg acc ggc agc ctc cgc 28350Thr Thr Glu Asn Thr Thr Glu Asn Ile Thr Ala Thr Gly Ser Leu Arg9375 938093859390cgc ggc gac aac gac acc cac cgc ttc ctc acc gcc ctc gcc cac acc 28398Arg Gly Asp Asn Asp Thr His Arg Phe Leu Thr Ala Leu Ala His Thr939594009405cac acc acc ggc att cgg aca ccc acc acc tgg cac cac cac tac acc 28446His Thr Thr Gly Ile Arg Thr Pro Thr Thr Trp His His His Tyr Thr941094159420caa acc cac ccc cac ccc cac aac cac cac ctc gac ctg ccc acc tac 28494Gln Thr His Pro His Pro His Asn His His Leu Asp Leu Pro Thr Tyr942594309435ccc ttc caa cac cag cac tac tgg ctc caa cca ccc acc acg aca acc 28542Pro Phe Gln His Gln His Tyr Trp Leu Gln Pro Pro Thr Thr Thr Thr944094459450gac ctc acc acc acc ggc ctc acc ccc acc cac cac ccc ctc ctc acc 28590Asp Leu Thr Thr Thr Gly Leu Thr Pro Thr His His Pro Leu Leu Thr9455 946094659470gca aca ctc acc ctc gcc aac aac aac aca caa cta ctc acc ggc cgc 28638Ala Thr Leu Thr Leu Ala Asn Asn Asn Thr Gln Leu Leu Thr Gly Arg947594809485ctc tcc cta cgc acc cac ccc tgg ctc acc gac cac acc gtc gtc ggt 28686Leu Ser Leu Arg Thr His Pro Trp Leu Thr Asp His Thr Val Val Gly949094959500acc act ctt gtg cca gga acc gcc ctc ctc gaa ctc gcc ctc caa gca 28734Thr Thr Leu Val Pro Gly Thr Ala Leu Leu Glu Leu Ala Leu Gln Ala950595109515acc acg acc gac cac ctc gaa gaa ctc gcc ctc cac acg cct ctc gtc 28782Thr Thr Thr Asp His Leu Glu Glu Leu Ala Leu His Thr Pro Leu Val952095259530atc ccc cgt gag ggt gcc gtc gac gtt cag gtg cac atc aat cca ccg 28830Ile Pro Arg Glu Gly Ala Val Asp Val Gln Val His Ile Asn Pro Pro9535 954095459550gac gac acc gac act cgt tca ctg acg atc tac tcg cga agc gag aac 28878Asp Asp Thr Asp Thr Arg Ser Leu Thr Ile Tyr Ser Arg Ser Glu Asn955595609565gcc ccc gca gcg gct ccc tgg cgt cat cac gcc acg gcc gtt ctg gga 28926Ala Pro Ala Ala Ala Pro Trp Arg His His Ala Thr Ala Val Leu Gly957095759580acc aag acc tcg cgc att gag aca ggc cgt agc cac gat gat ctg tcg 28974Thr Lys Thr Ser Arg Ile Glu Thr Gly Arg Ser His Asp Asp Leu Ser958595909595atg tgg ccg cca gcg ggc gca gtt cgc tgt gct gat gag gaa ttg gca 29022Met Trp Pro Pro Ala Gly Ala Val Arg Cys Ala Asp Glu Glu Leu Ala960096059610gcc ttg tat ggc gac tac gag gca aat ggc ttt gtc tat ggc ccc gca 29070Ala Leu Tyr Gly Asp Tyr Glu Ala Asn Gly Phe Val Tyr Gly Pro Ala9615 962096259630ttc cgg ggg ctg act gct gcc tgg cgt ctg gga gac gag gtg ttt gcc 29118Phe Arg Gly Leu Thr Ala Ala Trp Arg Leu Gly Asp Glu Val Phe Ala963596409645gag gtt cgc ctt cca gaa cag gtg cac ggc gag gca tcc gcg tac aac 29166Glu Val Arg Leu Pro Glu Gln Val His Gly Glu Ala Ser Ala Tyr Asn965096559660ctg cac ccg gca ctg ctg gat gct gcc ttg cac gca gcg gcc ttt gcg 29214Leu His Pro Ala Leu Leu Asp Ala Ala Leu His Ala Ala Ala Phe Ala966596709675ccg tcg ggc agt ctg ccg cag gga tcc gta ccg ttc tcc ttc acc ggt 29262Pro Ser Gly Ser Leu Pro Gln Gly Ser Val Pro Phe Ser Phe Thr Gly968096859690gtg acg ctg cac gcc gcc aat gcg tcg tcg ttg cgc gtg cga ctc tcg 29310Val Thr Leu His Ala Ala Asn Ala Ser Ser Leu Arg Val Arg Leu Ser9695 970097059710ccg gcc gat ccg aac agc ggc cac gcc gca gtt tcc gtg ctg gtc acg 29358Pro Ala Asp Pro Asn Ser Gly His Ala Ala Val Ser Val Leu Val Thr971597209725gat gac acc ggt acg ccc gtg gcg tcc gtc gag gcg ttg gcg gtg cgc 29406Asp Asp Thr Gly Thr Pro Val Ala Ser Val Glu Ala Leu Ala Val Arg973097359740ccg ttg gcg gcg gac gaa ttg cga gct gcc gag cgc gcc gta cag cgc 29454Pro Leu Ala Ala Asp Glu Leu Arg Ala Ala Glu Arg Ala Val Gln Arg974597509755gct gag ctc ttc gac atg aag tgg gtt gag gtg ccc tca gat gta ctg 29502Ala Glu Leu Phe Asp Met Lys Trp Val Glu Val Pro Ser Asp Val Leu976097659770gtg tcg ggc ggg gca tcg gtg gtg gtg ctg gat ggt gcc gac gac ctc 29550Val Ser Gly Gly Ala Ser Val Val Val Leu Asp Gly Ala Asp Asp Leu9775 978097859790gtt ggt ctg gcg gct gag gag gat ggt gtg ccg ggg gtg gtg gtg ttg 29598Val Gly Leu Ala Ala Glu Glu Asp Gly Val Pro Gly Val Val Val Leu979598009805cgg tgc ccg gat gcc ggt gcc gat ggc ggc ggt ggt ggc ggt ggt gtg 29646Arg Cys Pro Asp Ala Gly Ala Asp Gly Gly Gly Gly Gly Gly Gly Val981098159820ggt gag gtt gtt ggt ggg gtg ttg ggt gtg gtg cag ggg tgg ctg ggg 29694Gly Glu Val Val Gly Gly Val Leu Gly Val Val Gln Gly Trp Leu Gly982598309835ctg gag cgg ttt gcg ggt tcg cgg ctg gtg gtg gtg acc cgg ggt gcg 29742Leu Glu Arg Phe Ala Gly Ser Arg Leu Val Val Val Thr Arg Gly Ala984098459850gtg gtg gcc ggc ccg gag gac ggc ccg gtg gat ggc ccg gtg gat gtg 29790Val Val Ala Gly Pro Glu Asp Gly Pro Val Asp Gly Pro Val Asp Val9855 986098659870gtg ggt gcg gcg gtg tgg ggg ctg gtg cgg tcg gcg cag gct gag cat 29838Val Gly Ala Ala Val Trp Gly Leu Val Arg Ser Ala Gln Ala Glu His987598809885ccg gac cgg ttt gtc ctc ctc gac ctg gac acc gac ctc gac agc ggc 29886Pro Asp Arg Phe Val Leu Leu Asp Leu Asp Thr Asp Leu Asp Ser Gly989098959900gct gac cgc gat gcc ggc aac gag gcc ggt atg ggg tct ggt ctg gat 29934Ala Asp Arg Asp Ala Gly Asn Glu Ala Gly Met Gly Ser Gly Leu Asp990599109915ggt ggg cgt gtg gct gcg gtg gtg gcg tgt ggt gag ccg cag ttg gcg 29982Gly Gly Arg Val Ala Ala Val Val Ala Cys Gly Glu Pro Gln Leu Ala992099259930gtg cgt ggt gag cgg gtg ctg gcc gca cgc ctg aca cga ctt gag tcg 30030Val Arg Gly Glu Arg Val Leu Ala Ala Arg Leu Thr Arg Leu Glu Ser9935 994099459950ccg gtt gat gta tcg ggt cgg gag gtg ttg ccg tgg ttg tcg ggt ggg 30078Pro Val Asp Val Ser Gly Arg Glu Val Leu Pro Trp Leu Ser Gly Gly995599609965tcg gtg ttg gtg acg ggt ggg acg ggt gtg ctg ggt gcg gcg gtg gcg 30126Ser Val Leu Val Thr Gly Gly Thr Gly Val Leu Gly Ala Ala Val Ala997099759980cgg cat ctg gct ggt gtg tgt ggg gtg cgg gat ctg ttg ttg gtg agc 30174Arg His Leu Ala Gly Val Cys Gly Val Arg Asp Leu Leu Leu Val Ser998599909995cgg cgt ggt ccg gat gct ccg ggt gcg gag ggt ttg cgg gcg gag ctg 30222Arg Arg Gly Pro Asp Ala Pro Gly Ala Glu Gly Leu Arg Ala Glu Leu10000 10005 10010gcc gcg ttg ggg gcg gag gtg cgg att gtt gcg tgt gat gtg ggg gag 30270Ala Ala Leu Gly Ala Glu Val Arg Ile Val Ala Cys Asp Val Gly Glu10015 10020 10025 10030cgg cgg gag gtg gtc cgg ctg ctg gag ggt gtt cct gcc ggg tgt ccg 30318Arg Arg Glu Val Val Arg Leu Leu Glu Gly Val Pro Ala Gly Cys Pro10035 10040 10045ctg acg ggt gtc gtg cat gcg gct ggt gtg ctg gac gat gcg acg atc 30366Leu Thr Gly Val Val His Ala Ala Gly Val Leu Asp Asp Ala Thr Ile10050 10055 10060gcc tct ctc acg ccc gag cgg ctg ggc acg gtg ttc gcg gcc aag gtg 30414Ala Ser Leu Thr Pro Glu Arg Leu Gly Thr Val Phe Ala Ala Lys Val10065 10070 10075gat gcc gct ctt ttg ctg gat gag ctg acg cgg ggt atg gag ctg tcg 30462Asp Ala Ala Leu Leu Leu Asp Glu Leu Thr Arg Gly Met Glu Leu Ser10080 10085 10090gcg ttc gtg ctg ttc tcc tcg gcc gcg ggg atc ctg ggg tcg gcc ggg 30510Ala Phe Val Leu Phe Ser Ser Ala Ala Gly Ile Leu Gly Ser Ala Gly10095 10100 10105 10110cag ggc aac tac gcc gcg gcc aat gcc gct ctg gac gcg ctg gcg tac 30558Gln Gly Asn Tyr Ala Ala Ala Asn Ala Ala Leu Asp Ala Leu Ala Tyr10115 10120 10125cgg cgg cgg gcg gcg ggt ctg ccg ggg gtg tcg ctg gcg tgg ggg ctg 30606Arg Arg Arg Ala Ala Gly Leu Pro Gly Val Ser Leu Ala Trp Gly Leu10130 10135 10140tgg gaa gag gcc agc ggg atg acc ggg cat ctg gcc ggc acc gac cac 30654Trp Glu Glu Ala Ser Gly Met Thr Gly His Leu Ala Gly Thr Asp His10145 10150 10155cgg cgc atc atc cgt tcc ggt ctg cat ccc atg tcg acc ccg gac gca 30702Arg Arg Ile Ile Arg Ser Gly Leu His Pro Met Ser Thr Pro Asp Ala10160 10165 10170ctg gcc ctc ttc gat gcg gcc ctg gct ctg gac cgg ccg gtc ctg ctg 30750Leu Ala Leu Phe Asp Ala Ala Leu Ala Leu Asp Arg Pro Val Leu Leu10175 10180 10185 10190ccc gcc gac ctg cgt ccc gcc ccg ccc ctg ccg ccc ctg ctg cag gac 30798Pro Ala Asp Leu Arg Pro Ala Pro Pro Leu Pro Pro Leu Leu Gln Asp10195 10200 10205ctc ctg ccc gcc acc cgc cgc cgc acc acc cgc acc acc act acc ggt 30846Leu Leu Pro Ala Thr Arg Arg Arg Thr Thr Arg Thr Thr Thr Thr Gly10210 10215 10220ggt gcg gac aac ggc gcc cag ctg cac ggc cgg ctg gcc ggc cag aca 30894Gly Ala Asp Asn Gly Ala Gln Leu His Gly Arg Leu Ala Gly Gln Thr10225 10230 10235cac gaa caa cag cac acc acc ctc ctc gcc ctg gtc cgc tcc cac atc 30942His Glu Gln Gln His Thr Thr Leu Leu Ala Leu Val Arg Ser His Ile10240 10245 10250gcc acc gtc ctg ggc cac acc acc ccc gac acc atc ccc ccc gac cgc 30990Ala Thr Val Leu Gly His Thr Thr Pro Asp Thr Ile Pro Pro Asp Arg10255 10260 10265 10270gcg ttc cgc gac ctc ggc ttc gac tcc ctc acc gcc gtc gaa cta cgc 31038Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu Arg10275 10280 10285aac cgg ctc tcc cac acc acc gga ctc cgc ctc ccc acc acc ctc gcc 31086Asn Arg Leu Ser His Thr Thr Gly Leu Arg Leu Pro Thr Thr Leu Ala10290 10295 10300ttc gac cac ccc aac ccc acc acc ctc acc cac cac ctc cac aca caa 31134Phe Asp His Pro Asn Pro Thr Thr Leu Thr His His Leu His Thr Gln10305 10310 10315ctc gtc agc aag gga ctc acc gcc gcg gcc gag ccg gac gcc gca acg 31182Leu Val Ser Lys Gly Leu Thr Ala Ala Ala Glu Pro Asp Ala Ala Thr10320 10325 10330aca ccc ccg ggg ctg ccc tcg ctg ctc tcg gag ctc gag cgg ctg gag 31230Thr Pro Pro Gly Leu Pro Ser Leu Leu Ser Glu Leu Glu Arg Leu Glu10335 10340 10345 10350gcg gta gtg ctc tcc tcc acc aca tcc tcc gct gcc ccg ctg gac gac 31278Ala Val Val Leu Ser Ser Thr Thr Ser Ser Ala Ala Pro Leu Asp Asp10355 10360 10365ggc gcg cgc acg cgg ctg gcc tcc cga ctg cat tcc ctc gcc cag aag 31326Gly Ala Arg Thr Arg Leu Ala Ser Arg Leu His Ser Leu Ala Gln Lys10370 10375 10380ttg aac ggc gac gac acc gcc ccc gac ctc gca gag aca tcg gac gag 31374Leu Asn Gly Asp Asp Thr Ala Pro Asp Leu Ala Glu Thr Ser Asp Glu10385 10390 10395gag atg ttc gct ctc atc gac agg gaa gtc gga ttc gaa tct caa tga 31422Glu Met Phe Ala Leu Ile Asp Arg Glu Val Gly Phe Glu Ser Gln10400 10405 10410<210>3<211>3972<212>PRT<213>除蟲鏈霉菌<400>3Val Gln Arg Met Asp Gly Gly Glu Glu Pro Arg Pro Ala Ala Gly Glu1 5 10 15Val Leu Gly Val Ala Asp Glu Ala Asp Gly Gly Val Val Phe Val Phe20 25 30Pro Gly Gln Gly Pro Gln Trp Pro Gly Met Gly Arg Glu Leu Leu Asp35 40 45Ala Ser Asp Val Phe Arg Glu Ser Val Arg Ala Cys Glu Ala Ala Phe50 55 60Ala Pro Tyr Val Asp Trp Ser Val Glu Gln Val Leu Arg Asp Ser Pro65 70 75 80Asp Ala Pro Gly Leu Asp Arg Val Asp Val Val Gln Pro Thr Leu Phe85 90 95Ala Val Met Ile Ser Leu Ala Ala Leu Trp Arg Ser Gln Gly Val Glu100 105 110Pro Cys Ala Val Leu Gly His Ser Leu Gly Glu Ile Ala Ala Ala His115 120 125Val Ser Gly Gly Leu Ser Leu Ala Asp Ala Ala Arg Val Val Thr Leu130 135 140Trp Ser Gln Ala Gln Thr Thr Leu Ala Gly Thr Gly Ala Leu Val Ser145 150 155 160Val Ala Ala Thr Pro Asp Glu Leu Leu Pro Arg Ile Ala Pro Trp Thr165 170 175Glu Asp Asn Pro Ala Arg Leu Ala Val Ala Ala Val Asn Gly Pro Arg180 185 190Ser Thr Val Val Ser Gly Ala Arg Glu Ala Val Ala Asp Leu Val Ala195200 205Asp Leu Thr Ala Ala Gln Val Arg Thr Arg Met Ile Pro Val Asp Val210 215 220Pro Ala His Ser Pro Leu Met Tyr Ala Ile Glu Glu Arg Val Val Ser225 230 235 240Gly Leu Leu Pro Ile Thr Pro Arg Pro Ser Arg Ile Pro Phe His Ser245 250 255Ser Val Thr Gly Gly Arg Leu Asp Thr Arg Glu Leu Asp Ala Ala Tyr260 265 270Trp Tyr Arg Asn Met Ser Ser Thr Val Arg Phe Glu Pro Ala Ala Arg275 280 285Leu Leu Leu Gln Gln Gly Pro Lys Thr Phe Val Glu Met Ser Pro His290 295 300Pro Val Leu Thr Met Gly Leu Gln Glu Leu Ala Pro Asp Leu Gly Asp305 310 315320Thr Thr Gly Thr Ala Asp Thr Val Ile Met Gly Thr Leu Arg Arg Gly325 330 335Gln Gly Thr Leu Asp His Phe Leu Thr Ser Leu Ala Gln Leu Arg Gly340 345 350His Gly Glu Thr Ser Ala Thr Thr Val Leu Ser Ala Arg Leu Thr Ala355 360 365Leu Ser Pro Thr Gln Gln Gln Ser Leu Leu Leu Asp Leu Val Arg Ala370 375 380His Thr Met Ala Val Leu Asn Asp Asp Gly Asn Glu Arg Thr Ala Ser385 390 395 400Asp Ala Gly Pro Ser Ala Ser Phe Ala His Leu Gly Phe Asp Ser Val405 410 415Met Gly Val Glu Leu Arg Asn Arg Leu Ser Lys Ala Thr Gly Leu Arg420 425 430Leu Pro Val Thr Leu Ile Phe Asp His Thr Thr Pro Ala Ala Val Ala435 440 445Ala Arg Leu Arg Thr Ala Ala Leu Gly His Leu Asp Glu Asp Thr Ala450 455 460Pro Val Pro Asp Ser Pro Ser Gly His Gly Gly Thr Ala Ala Ala Asp465 470 475 480Asp Pro Ile Ala Ile Ile Gly Met Ala Cys Arg Phe Pro Gly Gly Val485 490 495Arg Ser Pro Lys Asp Leu Trp Glu Leu Ala Ala Ser Gly Gly Asp Ala500 505 510Ile Gly Pro Phe Pro Thr Asp Arg Gly Trp Pro Thr Glu Gln Arg His515 520 525Ala Gln Asp Pro Thr Gln Pro Gly Thr Phe Tyr Pro Gln Gly Gly Gly
530 535 540Phe Leu His Asp Ala Ala His Phe Asp Ala Gly Phe Phe Gly Ile Ser545 550 555 560Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu565 570 575Thr Ser Trp Glu Ala Phe Glu Arg Ala Gly Ile Asp Pro Leu Ser Val580 585 590Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Ala Leu Ser Phe Asp Tyr595 600 605Gly Pro Arg Met Asp Thr Ala Ser Ser Glu Gly Ala Ala Asp Val Glu610 615 620Gly His Ile Leu Thr Gly Thr Thr Gly Ser Val Leu Ser Gly Arg Ile625 630 635 640Ala Tyr Ser Phe Gly Leu Glu Gly Pro Ala Ile Thr Val Asp Thr Gly645 650 655Cys Ser Ala Ser Leu Val Thr Leu His Leu Ala Cys Gln Ser Leu Arg660 665 670Ser Gly Glu Cys Thr Leu Ala Leu Ala Gly Gly Val Ser Val Met Ser675 680 685Thr Leu Gly Met Phe Ile Glu Phe Ser Arg Gln Arg Gly Leu Ser Val690 695 700Asp Gly Arg Cys Lys Ala Tyr Ser Ala Ala Ala Asp Gly Thr Gly Trp705 710 715 720Gly Glu Gly Val Gly Met Leu Leu Val Glu Arg Leu Ser Asp Ala Val725 730 735Arg Leu Gly His Arg Val Leu Ala Val Val Arg GlySer Ala Val Asn740 745750Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ala Gln755 760 765Glu Arg Val Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Ser Val Ala770 775 780Asp Val Asp Val Val Glu Gly His Gly Thr Gly Thr Thr Leu Gly Asp785 790 795 800Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Arg Ala Gly805 810 815Asp Arg Pro Leu Trp Leu Gly Ser Leu Lys Ser Asn Ile Gly His Thr820 825 830Met Ala Ala Ala Gly Val Gly Gly Val Ile Lys Met Val Met Ala Leu835 840 845Arg Glu Gly Val Leu Pro Arg Thr Leu His Val Asp Lys Pro Ser Pro850 855 860Gln Val Asp Trp Ser Ala Gly Ala Val Arg Leu Leu Thr Glu Ala Val865 870 875 880Pro Trp Pro Gly Asp Ala Ala Gly Arg Leu Arg Arg Ala Gly Val Ser885 890 895Ser Phe Gly Ile Gly Gly Thr Asn Ala His Val Ile Leu Glu Glu Ala900 905 910Pro Ala Ala Gly Gly Cys Val Ala Gly Gly Gly Val Leu Glu Gly Ala915 920 925Pro Gly Leu Ala Ile Ser Val Ala Glu Ser Val Ala Ala Pro Val Ala930 935 940Val Ser Ala Pro Val Ala Glu Ser Val Pro Val Pro Val Pro Val Pro945 950 955 960Val Pro Val Pro Val Ser Ala Arg Ser Glu Ala Gly Leu Arg Ala Gln965 970 975Ala Glu Ala Leu Arg Gln Tyr Val Ala Val Arg Pro Asp Val Ser Leu980 985 990Ala Asp Val Gly Ala Gly Leu Ala Cys Gly Arg Ala Val Leu Glu His99510001005Arg Ala Val Val Leu Ala Ala Asp Arg Glu Glu Leu Val Gln Gly Leu101010151020Gly Ala Leu Ala Ala Gly Glu Pro Asp Arg Arg Val Thr Thr Gly His1025 103010351040Ala Pro Gly Gly Asp Arg Gly Gly Val Val Phe Val Phe Pro Gly Gln104510501055Gly Gly Gln Trp Ala Gly Met Gly Val Arg Leu Leu Ala Ser Ser Pro106010651070Val Phe Ala Arg Arg Met Gln Ala Cys Glu Glu Ala Leu Ala Pro Trp107510801085Val Asp Trp Ser Val Val Asp Ile Leu Arg Arg Asp Ala Gly Asp Ala109010951100Val Trp Glu Arg Ala Asp Val Val Gln Pro Val Leu Phe Ser Val Met1105 111011151120Val Ser Leu Ala Ala Leu Trp Arg Ser Tyr Gly Ile Glu Pro Asp Ala112511301135Val Leu Gly His Ser Gln Gly Glu Ile Ala Ala Ala His Val Cys Gly114011451150Ala Leu Ser Leu Lys Asp Ala Ala Lys Thr Val Ala Leu Arg Ser Arg115511601165Ala Leu Ala Ala Val Arg Gly Arg Gly Gly Met Ala Ser Val Pro Leu117011751180Pro Ala Gln Glu Val Glu Gln Leu Ile Gly Glu Arg Trp Ala Gly Arg1185 119011951200Leu Trp Val Ala Ala Val Asn Gly Pro Arg Ser Thr Ala Val Ser Gly120512101215Asp Ala Glu Ala Val Asp Glu Val Leu Ala Tyr Cys Ala Gly Thr Gly122012251230Val Arg Ala Arg Arg Ile Pro Val Asp Tyr Ala Ser His Cys Pro His
123512401245Val Gln Pro Leu Arg Glu Glu Leu Leu Glu Leu Leu Gly Asp Ile Ser125012551260Pro Gln Pro Ser Gly Val Pro Phe Phe Ser Thr Val Glu Gly Thr Trp1265 127012751280Leu Asp Thr Thr Thr Leu Asp Ala Ala Tyr Trp Tyr Arg Asn Leu His128512901295Gln Pro Val Arg Phe Ser Asp Ala Val Gln Ala Leu Ala Asp Asp Gly130013051310His Arg Val Phe Val Glu Val Ser Pro His Pro Thr Leu Val Pro Ala131513201325Ile Glu Asp Thr Thr Glu Asp Thr Ala Glu Asp Val Thr Ala Ile Gly133013351340Ser Leu Arg Arg Gly Asp Asn Asp Thr Arg Arg Phe Leu Thr Ala Leu1345 135013551360Ala His Thr His Thr Thr Gly Ile Gly Thr Pro Thr Thr Trp His His136513701375His Tyr Thr His His His Thr His Pro His Pro His Thr His Leu Asp138013851390Leu Pro Thr Tyr Pro Phe Gln His Gln His Tyr Trp Leu Glu Ser Ser139514001405Gln Pro Gly Ala Gly Ser Gly Ser Gly Ala Gly Ala Gly Ser Gly Ala141014151420Gly Ser Gly Arg Ala Gly Thr Ala Gly Gly Thr Ala Glu Val Glu Ser1425 143014351440Arg Phe Trp Asp Ala Val Ala Arg Gln Asp Leu Glu Thr Val Ala Thr144514501455Thr Leu Ala Val Pro Pro Ser Ala Gly Leu Asp Thr Val Val Pro Ala146014651470Leu Ser Ala Trp His Arg His Gln His Asp Gln Ala Arg Ile Asn Thr147514801485Trp Thr Tyr Gln Glu Thr Trp Lys Pro Leu Thr Leu Pro Thr Thr His149014951500Gln Pro His Gln Thr Trp Leu Ile Ala Ile Pro Glu Thr Gln Thr His1505 151015151520His Pro His Ile Thr Asn Ile Leu Thr Asn Leu His His His Gly Ile152515301535Thr Pro Ile Pro Leu Thr Leu Asn His Thr His Thr Asn Pro Gln His154015451550Leu His His Thr Leu His His Thr Arg Gln Gln Ala Gln Asn His Thr1555 1560 1565Thr Gly Ala Ile Thr Gly Leu Leu Ser Leu Leu Ala Leu Asp Glu Thr157015751580Pro His Pro His His Pro His Thr Pro Thr Gly Thr Leu Leu Asn Leu1585 159015951600Thr Leu Thr Gln Thr His Thr Gln Thr His Pro Pro Thr Pro Leu Trp160516101615Tyr Ala Thr Thr Asn Ala Thr Thr Thr His Pro Asn Asp Pro Leu Thr162016251630His Pro Thr Gln Ala Gln Thr Trp Gly Leu Ala Arg Thr Thr Leu Leu163516401645Glu His Pro Thr His Thr Ala Gly Ile Ile Asp Leu Pro Thr Thr Pro165016551660Thr Pro His Thr Leu Gln His Leu Thr Gln Thr Leu Thr Gln Pro His1665 167016751680His Gln Thr Gln Leu Ala Ile Arg Thr Thr Gly Thr His Thr Arg Arg168516901695Leu Thr Pro Thr Thr Leu Thr Pro Thr His Gln Pro Pro Thr Pro Thr170017051710Pro His Gly Thr Thr Leu Ile Thr Gly Gly Thr Gly Ala Leu Ala Thr171517201725His Leu Thr His His Leu Thr Thr His Gln Pro Thr Gln His Leu Leu173017351740Leu Thr Ser Arg Thr Gly Pro His Thr Pro His Ala Gln His Leu Thr1745 175017551760Thr Gln Leu Gln Gln Lys Gly Ile His Leu Thr Ile Thr Thr Cys Asp176517701775Thr Ser Asn Pro Asp Gln Leu Gln Gln Leu Leu Asn Thr Ile Pro Pro178017851790Gln His Pro Leu Thr Thr Val Ile His Thr Ala Gly Ile Leu Asp Asp179518001805Ala Thr Leu Thr Asn Leu Thr Pro Thr Gln Leu Asn Asn Val Leu Arg181018151820Ala Lys Ala His Ser Ala His Leu Leu His Gln Leu Thr Gln His Thr1825 183018351840Pro Leu Thr Ala Phe Val Leu Tyr Ser Ser Ala Ala Ala Thr Phe Gly184518501855Ala Pro Gly Gln Ala Asn Tyr Ala Ala Ala Asn Ala Tyr Leu Asp Ala186018651870Leu Ala His His Arg His Thr His His Leu Pro Ala Thr Ser Ile Ala187518801885Trp Gly Thr Trp Gln Gly Asn Gly Leu Ala Asp Ser Asp Lys Ala Arg189018951900Ala Tyr Leu Asp Arg Arg Gly Phe Arg Pro Met Ser Pro Glu Leu Ala1905 191019151920Thr Ala Ala Val Thr Gln Ala Ile Ala Asp Thr Glu Arg Pro Tyr Val192519301935Val Ile Ala Asp Ile Asp Trp Ser Lys Ile Glu His Thr Ser Gln Thr
194019451950Ser Asp Leu Val Ser Ala Ala Arg Glu Arg Glu Pro Ala Val Gln Arg195519601965Pro Thr Pro Pro Ala Glu Leu His Lys Thr Leu Ala His Gln Thr Ser197019751980Ala Asp Gln Arg Ala Ala Leu Leu Glu Leu Val Arg Asp His Val Ala1985 199019952000Ala Val Leu Arg His Ala Asp Pro Lys Ala Ile Ala Pro Asp Gln Ser200520102015Phe Arg Ala Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Phe Arg Asn202020252030Leu Leu Ile Lys Ala Thr Gly Leu Arg Leu Pro Val Ser Leu Val Phe203520402045Asp His Pro Thr Pro Ala Lys Leu Ala Val His Leu Gln Asn Gln Leu205020552060Arg Gly Thr Ala Ala Glu Ser Ala Pro Ser Ala Ala Ala Val Thr Ala2065 207020752080Glu Ala Ser Val Thr Glu Pro Ile Ala lle Val Gly Met Ala Cys Arg208520902095Phe Pro Gly Gly Val Thr Ser Ala Asp Asp Phe Trp Asp Leu Ile Ser210021052110Ser Glu Gln Asp Ala Ile Gly Gly Phe Pro Thr Asp Arg Gly Trp Asp211521202125Leu Asp Thr Leu Tyr Asp Pro Asp Pro Asp His Pro Gly Thr Cys Tyr213021352140Thr Arg Asn Gly Gly Phe Leu Tyr Asp Ala Gly His Phe Asp Ala Glu2145 215021552160Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln216521702175Arg Leu Leu Leu Glu Thr Ala Trp Glu Thr Ile Glu His Ala Gly Ile218021852190Asn Pro His Thr Leu His Gly Thr Pro Thr Gly Val Phe Thr Gly Thr219522002205Asn Gly Gln Asp Tyr Ala Leu Arg Val His Asn Ala Gly Gln Ser Thr221022152220Asp Gly Phe Ala Leu Thr Gly Thr Ala Gly Ser Val Ile Ser Gly Arg2225 223022352240Ile Ser Tyr Thr Phe Gly Phe Glu Gly Pro Ala Val Ser Val Asp Thr224522502255Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys Gln Ala Leu226022652270Arg Ala Gly Glu Cys Ser Met Ala Leu Ala Gly Gly Val Thr Val Met227522802285Ser Ser Pro Gly Ala Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala229022952300Ala Asp Gly His Cys Lys Ala Phe Ser Ala Ala Ala Asp Gly Thr Gly2305 231023152320Trp Gly Glu Gly Val Gly Met Leu Leu Val Glu Arg Leu Ser Asp Ala232523302335His Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val234023452350Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser235523602365Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Ser Ala237023752380Gly Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Thr Leu Gly2385 239023952400Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Asp Arg240524102415Ala Gly Glu Gly Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Val Gly242024252430His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met243524402445Ala Leu Arg His Gly Leu Leu Pro Arg Thr Leu His Val Asp Glu Pro245024552460Ser Pro His Val Asp Trp Ser Ala Gly Ala Val Gln Leu Leu Thr Glu2465 247024752480Thr Val Pro Trp Pro Gly Gly Glu Gly Arg Leu Arg Arg Ala Gly Val248524902495Ser Ser Phe Gly Val Ser Gly Thr Asn Ala His Val Ile Leu Glu Glu250025052510Ala Pro Ala Asp Asp Val Pro Gly Gly Pro Pro Ala Gly Glu Gly Asp251525202525Ala Gly Ser Asp Asp Glu Ala Ala Ala Gly Ser Pro Gly Val Trp Pro253025352540Trp Leu Val Ser Ala Lys Ser Gln Pro Ala Leu Arg Ala Gln Ala Gln2545 255025552560Ala Leu His Ala His Leu Thr Asp His Pro Gly Leu Asp Leu Ala Asp256525702575Val Gly Tyr Thr Leu Ala His Ala Arg Ala Val Phe Asp His Arg Ala258025852590Thr Leu Ile Ala Ala Asp Arg Asp Thr Phe Leu Gln Ala Leu Gln Ala259526002605Leu Ala Ala Gly Glu Pro His Pro Ala Val Ile His Ser Ser Ala Pro261026152620Gly Gly Thr Gly Thr Gly Glu Ala Ala Gly Lys Thr Ala Phe Ile Cys2625 263026352640Ser Gly Gln Gly Thr Gln Arg Pro Gly Met Ala His Gly Leu Tyr His
264526502655Thr His Pro Val Phe Ala Ala Ala Leu Asn Asp Ile Cys Thr His Leu266026652670Asp Pro His Leu Asp His Pro Leu Leu Pro Leu Leu Thr Gln Asn Asp267526802685Asn Asp Asn Glu Asp Ala Ala Ala Leu Leu Gln Gln Thr Arg Tyr Ala269026952700Gln Pro Ala Leu Phe Ala Phe Gln Val Ala Leu His Arg Leu Leu Thr2705 271027152720Asp Gly Tyr His Ile Thr Pro His Tyr Tyr Ala Gly His Ser Leu Gly272527302735Glu Ile Thr Ala Ala His Leu Ala Gly Ile Leu Thr Leu Thr Asp Ala274027452750Thr Thr Leu Ile Thr Gln Arg Ala Thr Leu Met Gln Thr Met Pro Pro275527602765Gly Thr Met Thr Thr Leu His Thr Thr Pro His His Ile Thr His His277027752780Leu Thr Ala His Glu Asn Asp Leu Ala Ile Ala Ala Ile Asn Thr Pro2785 279027952800Thr Ser Leu Val Ile Ser Gly Thr Pro His Thr Val Gln His Ile Thr280528102815Thr Leu Cys Gln Gln Gln Gly Ile Lys Thr Lys Thr Leu Pro Thr Asn282028252830His Ala Phe His Ser Pro His Thr Asn Pro Ile Leu Asn Gln Leu His283528402845Gln His Thr Gln Thr Leu Thr Tyr His Pro Pro His Thr Pro Leu Ile285028552860Thr Ala Asn Thr Pro Pro Asp Gln Leu Leu Thr Pro His Tyr Trp Thr2865 287028752880Gln Gln Ala Arg Asn Thr Val Asp Tyr Ala Thr Thr Thr Gln Thr Leu
288528902895His Gln His Gly Val Thr Thr Tyr Ile Glu Leu Gly Pro Asp Asn Thr290029052910Leu Thr Thr Leu Thr His His Asn Leu Pro Asn Pro Pro Thr Thr Thr291529202925Leu Thr Leu Thr His Pro His His His Pro Gln Thr His Leu Leu Thr293029352940Asn Leu Ala Lys Thr Thr Thr Thr Trp His Pro His His Tyr Thr His2945 295029552960His Asp Asn Gln Pro His Thr His Thr His Leu Asp Leu Pro Thr Tyr296529702975Pro Phe Gln His His His Tyr Trp Leu Glu Ser Thr Gln Pro Gly Ala298029852990Gly Asn Val Ser Ala Ala Gly Leu Asp Pro Thr Glu His Pro Leu Leu299530003005Gly Ala Thr Leu Glu Leu Ala Thr Asp Gly Gly Ala Leu Leu Ala Gly301030153020Arg Leu Ser Leu Arg Ser His Pro Trp Leu Ala Asp His Ala Val Gly3025 303030353040Gly Thr Val Leu Leu Ser Gly Ala Thr Phe Leu Glu Leu Ala Leu His304530503055Ala Gly Thr Tyr Val Gly Cys Asp Arg Val Asp Glu Leu Thr Leu His306030653070Ala Pro Leu Val Val Pro Val Asp Gly Gly Val Ser Val Gln Val Gly307530803085Val Ala Ala Ala Asp Gly Glu Gly Arg Arg Leu Val Ser Val Tyr Ala309030953100Arg Gly Gly Ser Ala Cys Gly Gly Gly Gly Ala Ser Gly Gly Val Trp3105 311031153120Thr Cys His Ala Ser Gly Val Leu Val Glu Ala Ala Ala Gly Gly Val312531303135Val Val Asp Gly Leu Ala Gly Val Trp Pro Pro Arg Gly Ala Val Ala314031453150Val Asp Val Asp Gly Val Arg Asp Arg Leu Ala Gly Ala Gly Cys Val315531603165Leu Gly Pro Val Phe Ser Gly Leu Arg Ala Val Trp Arg Asp Gly Gly317031753180Asp Leu Leu Ala Glu Val Cys Leu Pro Glu Glu Ala Trp Gly Asp Ala3185 319031953200Ala Gly Phe Gly Leu His Pro Ala Leu Leu Asp Gly Val Val Gln Pro320532103215Leu Ser Val Leu Leu Pro Gly Gly Thr Gly Phe Gly Glu Gly Ala Gly322032253230Phe Gly Glu Gly Val Arg Val Pro Ala Val Trp Gly Gly Val Ser Leu323532403245His Arg Ala Gly Val Thr Gly Val Arg Val Arg Val Ser Ala Val Gly325032553260Arg Gly Gly Gly Arg Glu Ala Val Ser Val Val Val Gly Asp Glu Ala3265 327032753280Gly Val Pro Val Ala Ser Val Asp Arg Leu Glu Leu Arg Pro Val Asp328532903295Met Gly Gln Leu Arg Ala Val Ser Val Ser Ala Gly Arg Arg Gly Ser330033053310Leu Tyr Ala Val Gln Trp Ala Glu Val Gly Pro Val Pro Val Cys Gly331533203325Gln Ala Trp Ala Trp His Glu Asp Val Gly Glu Ser Gly Gly Gly Pro333033353340Val Pro Gly Val Val Val Leu Arg Cys Pro Asp Ala Gly Ala Gly Gly3345 335033553360Gly Gly Gly Gly Gly Gly Gly Gly Gly Val Gly Glu Val Val Gly Gly336533703375Val Leu Gly Val Val Gln Gly Trp Leu Gly Leu Glu Arg Phe Ala Gly338033853390Ser Arg Leu Val Val Val Thr Arg Gly Ala Val Val Ala Gly Pro Glu339534003405Asp Gly Pro Val Asp Val Val Gly Ala Ser Val Trp Gly Leu Val Arg341034153420Ser Ala Gln Ala Glu His Pro Asp Arg Phe Val Leu Leu Asp Leu Asp3425 343034353440Thr Asp Thr Gly Thr Asp Leu Asp Thr Gly Ala Gly Ala Gly Trp Gly344534503455Val Asp Gly Gly Arg Val Ala Ala Val Val Ala Cys Gly Glu Pro Gln346034653470Leu Ala Val Arg Gly Glu Arg Leu Leu Ala Ala Arg Leu Lys Arg Leu347534803485Glu Ser Ser Gly Asp Val Pro Ala Gln Arg Ser Gly Asp Thr Arg Ala349034953500Arg Arg Ser Asp Val Pro Ala Gln Arg Ser Gly Gly Val Pro Ala Arg3505 351035153520Arg Ser Val Asp Val Ser Gly Arg Glu Val Leu Pro Trp Leu Ser Gly352535303535Gly Ser Val Leu Val Thr Gly Gly Thr Gly Val Leu Gly Ala Ala Val354035453550Ala Arg His Leu Ala Gly Val Cys Gly Val Arg Asp Leu Leu Leu Val355535603565Ser Arg Arg Gly Pro Asp Ala Pro Gly Ala Glu Gly Leu Arg Ala Glu357035753580Leu Ala Ala Leu Gly Ala Glu Val Arg Ile Val Ala Cys Asp Val Gly3585 359035953600Glu Arg Arg Glu Val Val Arg Leu Leu Glu Gly Val Pro Ala Gly Cys360536103615Pro Leu Thr Gly Val Val His Ala Ala Gly Val Leu Asp Asp Ala Thr362036253630lle Ala Ser Leu Thr Pro Glu Arg Leu Gly Thr Val Phe Ala Ala Lys363536403645Val Asp Ala Ala Leu Leu Leu Asp Glu Leu Thr Arg Gly Met Glu Leu365036553660Ser Ala Phe Val Leu Phe Ser Ser Ala Ala Gly Ile Leu Gly Ser Ala3665 367036753680Gly Gln Gly Asn Tyr Ala Ala Ala Asn Ala Ala Leu Asp Ala Leu Ala368536903695Tyr Arg Arg Arg Ala Ala Gly Leu Pro Gly Val Ser Leu Ala Trp Gly370037053710Leu Trp Glu Glu Ala Ser Gly Met Thr Gly His Leu Ala Gly Thr Asp371537203725His Arg Arg Ile Ile Arg Ser Gly Leu His Pro Met Ser Thr Pro Asp373037353740Ala Leu Ala Leu Phe Asp Ala Ala Leu Ala Leu Asp Arg Pro Val Leu3745 375037553760Leu Pro Ala Asp Leu Arg Pro Ala Pro Pro Leu Pro Pro Leu Leu Gln376537703775Asp Leu Leu Pro Ala Thr Arg Arg Arg Thr Thr Arg Thr Thr Thr Thr378037853790Gly Gly Ala Asp Asn Gly Ala Gln Leu His Ala Arg Leu Ala Gly Gln379538003805Thr His Glu Gln Gln His Thr Thr Leu Leu Ala Leu Val Arg Ser His381038153820Ile Ala Thr Val Leu Gly His Thr Thr Pro Asp Thr Ile Pro Pro Asp3825 383038353840Arg Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu384538503855Arg Asn Arg Leu Ser Arg Thr Thr Gly Leu Arg Leu Pro Thr Thr Leu386038653870Als Phe Asp His Pro Asn Pro Thr Thr Leu Thr His His Leu His Thr387538803885Gln Leu Gln Pro Gln Pro Asp Asn Ala Val Ala Pro Val Leu Ala Glu389038953900Leu Asp Lys Leu Glu Ser Ala Leu Ser Ala Leu Asp Lys Thr Asp Ser3905 391039153920Ala Ser Glu Arg Val Thr Leu Arg Leu Lys Ser Leu Met Leu Arg Trp392539303935Asn Ala Pro Gln His Pro Thr Ala Glu Ser Ala Asp Asp Asp Glu Lys394039453950Phe Thr Ser Ala Thr Glu Ala Glu Ile Phe Lys Phe Ile Asp Asn Asp395539603965Leu Gly Leu Ser3970<210>4<211>6239<212>PRT<213>除蟲鏈霉菌<400>4Met Gln Leu Ala Asn Glu Ala Lys Leu Leu Glu Tyr Leu Lys Arg Val1 5 10 15Thr Ala Asp Leu Asp Arg Thr Arg Arg Arg Leu Tyr Glu Val Val Glu20 25 30Arg Glu Gln Glu Pro Ile Ala Ile Val Gly Met Ala Cys Arg Tyr Pro
35 40 45Gly Gly Ala Thr Ser Pro Thr Arg Leu Trp His Leu Val Lys Ser Gln50 55 60Thr Asp Ala lle Gly Glu Phe Pro Thr Asp Arg Gly Trp Asn Leu Glu65 70 75 80Gln Leu Tyr Asp Pro Asp Pro Asp Arg Ser Gly Thr Ser Tyr Thr Arg85 90 95Ser Gly Gly Phe Leu Tyr Asp Ala Gly Asp Phe Asp Ala Ala Phe Phe100 105 110Glu Leu Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu115 120 125Leu Leu Glu Thr Thr Trp Glu Thr Phe Glu Gln Gly Gly Ile Asp Pro130 135 140Arg Ser Met Arg Gly Ser Arg Thr Gly Val Phe Val Gly Ile Asn Pro145 150 155 160Glu Asp Tyr Thr Thr Gly Tyr Thr His Gln Pro Ser Asn Ala Val Glu165 170 175Gly Tyr Leu Leu Thr Gly Ser Ala Ala Ser Ile Ala Ser Gly Arg Ile180 185 190Ser Tyr Asn Phe Gly Leu Glu Gly Pro Ala Ile Thr Ile Asp Thr Ala195 200 205Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys Gln Ala Leu Arg210 215 220Ser Gly Glu Cys Thr Met Ala Leu Ala Gly Gly Ala Ser Val Met Ala225 230 235 240Thr Pro Phe Val Phe Thr Glu Phe Ser Arg Gln Arg Gly Leu Ala Ala245 250 255Asp Gly Arg Cys Lys Ala Phe Ser Ala Ala Ala Asp Gly Thr Gly Trp260 265 270Ser Glu Gly Val Gly Met Leu Leu Val Glu Arg Leu Ser Asp Ala Arg275 280 285Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn290 295 300Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Arg Ser Gln305 310 315 320Val Lys Val Ile Arg Gln Ala Leu Ala Asn Ala His Leu Ser Pro Ala325 330 335Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Thr Leu Gly Asp340 345 350Pro Ile Glu Ala Gln Ala Leu Val Glu Ala Tyr Gly Gln Asp Arg Pro355 360 365Asn Gly Arg Pro Leu Trp Leu Gly Thr Leu Lys Ser Asn Ile Gly His370 375 380Ser Met Ala Ala Ala Gly Val Gly Gly Val Ile Lys Met Val Met Ala385 390 395 400Leu Arg Asn Gly Leu Leu Pro Arg Thr Leu His Val Asp Glu Pro Ser405 410 415Pro His Val Asp Trp Ser Ala Gly Ala Val Gln Leu Leu Thr Glu Thr420 425 430Val Pro Trp Pro Gly Gly Glu Gly Arg Leu Arg Arg Ala Gly Val Ser435 440 445Ser Phe Gly Val Ser Gly Thr Asn Ala His Val Ile Leu Glu Glu Ala450 455 460Pro Ala His Asn Ile Pro Ser Asp Thr Pro Ala Asp Asp Val Pro Gly465 470 475 480Glu Ser Ala Ala Asp Glu Asp Ala Gly Ser Gly Asp Glu Ala Ala Ala485 490 495Gly Ser Pro Gly Val Trp Pro Trp Leu Val Ser Ala Lys Ser Gln Pro500 505 510Ala Leu Arg Ala Gln Ala Gln Ala Leu His Ala His Leu Thr Asp His515 520 525Pro Gly Leu Asp Leu Ala Asp Val Gly Tyr Thr Leu Ala His Ala Arg530 535 540Ala Val Phe Asp His Arg Ala Thr Leu lle Ala Ala Asp Arg Asp Thr545 550 555 560Phe Leu Gln Ala Leu Gln Ala Leu Ala Ala Gly Glu Pro His Pro Ala565 570 575Val Ile His Ser Ser Ala Pro Gly Gly Thr Gly Thr Gly Glu Ala Ala580 585 590Gly Lys Thr Ala Phe Ile Cys Ser Gly Gln Gly Thr Gln Arg Pro Gly595 600 605Met Ala His Gly Leu Tyr His Thr His Pro Val Phe Ala Ala Ala Leu610 615 620Asn Asp Ile Cys Thr His Leu Asp Pro His Leu Asp His Pro Leu Leu625 630 635 640Pro Leu Leu Thr Gln Asp Pro Asn Thr Gln Asp Thr Thr Thr Leu Glu645 650 655Glu Ala Ala Ala Leu Leu Gln Gln Thr Arg Tyr Ala Gln Pro Ala Leu660 665 670Phe Ala Phe Gln Val Ala Leu His Arg Leu Leu Thr Asp Gly Tyr His675 680 685Ile Thr Pro His Tyr Tyr Ala Gly His Ser Leu Gly Glu Ile Thr Ala690 695 700Ala His Leu Ala Gly Ile Leu Thr Leu Thr Asp Ala Thr Thr Leu Ile705 710 715 720Thr Gln Arg Ala Thr Leu Met Gln Thr Met Pro Pro Gly Thr Met Thr725 730 735Thr Leu His Thr Thr Pro His His Ile Thr His His Leu Thr Ala His
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Val Gly Val Val His Thr Ala Ala Val His Ala560556105615Ala Ala Ala Gln Met Leu Ala Arg Leu Gln Ala Trp Leu Gly Asp Glu562056255630Arg Leu Ala Asp Ser Arg Leu Leu Val Leu Thr Cys Gly Ala Val Ala563556405645Arg Ala Ser Gly Asp Asp Ala Thr Asp Leu Pro Gly Ala Ala Val Trp565056555660Gly Leu Val Arg Ser Ala Gln Ser Glu His Pro Asp Arg Ile Thr Leu5665 567056755680Leu Asp Phe Glu Arg Gly Thr Glu Ala Glu Pro Gly Gln Leu Ala Thr568556905695Ala Leu Asn Cys Gly Glu Arg Gln Leu Ala Val Arg Pro Gly Gly Leu570057055710Phe Thr Pro Arg Leu Val Arg Ala Pro Arg Val Ala Asp Ala Val Pro571557205725Ala Val Pro Ala Val Ala Val Pro Ser Ala Gly His Ala Ala Val Pro573057355740Ala Ala Gly Pro Phe Leu Pro Gly Gly Thr Val Leu Ile Thr Gly Gly5745 575057555760Thr Gly Val Leu Gly Arg Leu Val Ala Arg His Leu Val Glu Ala His576557705775Gly Val Arg His Leu Leu Leu Ala Gly Arg Arg Gly Pro Asp Ala Glu578057855790Gly Ala Pro Glu Leu Arg Ala Glu Leu Gly Gly Leu Gly Ala Thr Val579558005805Glu Val Val Ala Cys Asp Ala Ala Asp Arg Gln Gln Leu Ala Asp Leu581058155820Leu Thr Arg Ile Pro Asp Asp Arg Pro Leu Thr Gly Val Val His Ser5825 583058355840Ala Gly Ile Leu Asp Asp Gly Val Ile Thr Ser Leu Ser Pro Glu Arg584558505855Leu Gly Ala Val Leu Arg Ala Lys Ala Asp Ala Ala Leu Leu Leu Asp586058655870Glu Leu Thr Arg Gly Ala Glu Leu Ser Ala Phe Val Met Phe Ser Ser587558805885Ala Ser Ala Val Val Gly Ser Pro Gly Gln Gly Asn Tyr Ala Ala Ala589058955900Asn Ala Val Leu Asp Phe Leu Ala His Arg Arg Arg Ala Glu Gly Leu5905 591059155920Pro Ala Val Ser Leu Ala Trp Gly Leu Trp Glu Glu Gly Thr Gly Met592559305935Thr Gly His Leu Asp Val Asp Asp His Ala Arg Ile Ser Arg Ala Gly594059455950Met Arg Pro Leu Pro Thr Ala Glu Ala Leu Ala Leu Phe Asp Ala Ala595559605965Leu Ala Asp Gly Glu Pro Phe Leu Met Pro Ala Arg Leu Asp Leu Thr597059755980Ala Val Arg Ser Gly Ala Ala Ser Ala Pro Val Pro Pro Leu Leu Gln5985 599059956000Gly Leu Leu Gln Leu Pro Arg Ser Arg Ser Ala Ala Ala Ala Pro Gly600560106015His Gly Ala Pro Ala Ala Asp Glu Ala Ala Ala Trp Arg Glu Arg Leu602060256030Ala Arg Gln Ser Ala Gly Glu Arg Arg Gln Ala Leu Leu Arg Leu Val603560406045Arg Ser His Val Ala Ala Val Leu Gly His Ser Gly Ala Asp Gly Ile605060556060Asp Ala Ser Arg Ala Phe Arg Glu Leu Gly Phe Asp Ser Leu Thr Ala6065 607060756080Val Glu Leu Arg Asn Arg Leu Thr Ala Ala Thr Gly Leu Arg Leu Arg608560906095Ala Thr Leu Ala Phe Asp Phe Pro Thr Pro Ala Ala Leu Ala Glu His610061056110Leu Gly Glu Arg Leu Leu Pro Asp Gln Glu Ala Thr Gly Glu Gln Ala611561206125Gly Asp Gln Leu Ser Gly Gly Ser Glu Glu Asp Val Arg Ser Leu Leu613061356140Thr Ser Ile Pro Ile Gly Arg Leu Arg Asp Ala Gly Leu Leu Gly Pro6145 615061556160Leu Leu Thr Leu Ala Asp Thr Gly Arg Gly Ala Ser Gly Ala Ala Ala616561706175Gly Pro Glu Asp Ala Pro Pro Ser Gly Gln Asp Thr Pro Ala Pro Val618061856190Ser Ile Asp Glu Met Asp Ile Asp Asp Leu Met Asp Leu Ala His Gly619562006205His Gly Thr Ala Pro Ala Arg Glu Pro Ala Asp Ala Glu Asp Ser Ser621062156220Ser Ser Arg Asn Arg Thr His His Thr His Glu Gly Glu Thr Ala6225 62306235<210>5<211>4881<212>PRT<213>除蟲鏈霉菌<400>5Met Ala Asn Glu Glu Lys Leu Arg Asp Tyr Leu Lys Arg Val Thr Ala1 5 10 15Asp Leu Leu Asn Val Arg Arg Arg Leu Gln Gln Ile Glu Ser Gly Glu20 25 30Gln Glu Pro Ile Ala Ile Val Gly Met Ala Cys Arg Phe Pro Gly Gly35 40 45Val Glu Ser Ala Glu Asp Phe Trp Glu Leu Ile Ala Ser Gly Arg Asp50 55 60Ala Val Gly Glu Phe Pro Val Asp Arg Gly Trp Asp Val Glu Ala Phe65 70 75 80Tyr Asp Pro Glu Pro Gly Arg Ala Gly Ser Ser Tyr Thr Arg Arg Gly85 90 95Gly Phe Leu Glu Gly Ala Ala Glu Phe Asp Ala Gly Phe Phe Gly Ile100 105 110Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Met Leu115 120 125Glu Val Ser Trp Glu Ala Leu Glu Arg Ala Gly Ile Asp Pro Ala Thr130 135 140Leu Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Leu Met Ser Gln Asp145 150 155 160Tyr Ala Thr Arg Leu Leu Ser Val Pro Asp Asp Leu Ala Gly Tyr Leu165 170 175Gly Asn Gly Asn Ala Gly Ser Ile Leu Ser Gly Arg Val Ala Tyr Thr180 185 190Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser195 200 205Ser Leu Val Ala Leu His Leu Ala Cys Gln Ser Leu Arg Thr Gly Glu210 215 220Ser Ser Phe Ala Leu Ala Gly Gly Val Thr Val Met Ser Thr Pro Gly225 230 235 240Met Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ser Pro Asp Gly Arg245 250 255Cys Lys Ala Tyr Ala Ser Ala Ala Asp Gly Thr Gly Met Ser Glu Gly260 265 270Val Gly Ile Leu Leu Leu Glu Arg Leu Ser Glu Ala Glu Arg Arg Gly275 280 285His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly290 295 300Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val305 310 315 320Ile Arg Gln Ala Leu Ala Cys Ala Gly Leu Ser Val Ala Asp Val Asp325 330 335Val Val Glu Gly His Gly Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu340 345 350Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Arg Ala Gly Asp Thr Pro355 360 365Val Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Ala Gln Ala Ala370 375 380Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ala Leu Arg Ala Gly385 390 395 400Val Leu Pro Arg Thr Leu His Val Asp Glu Pro Ser Ser Gln Val Asp405 410 415Trp Ser Ser Gly Ser Val Arg Val Leu Ala Asp Glu Val Glu Trp Pro420 425 430Gly Val Glu Gly Arg Leu Arg Arg Ala Gly Val Ser Ala Phe Gly Val435 440 445Ser Gly Thr Asn Ala His Val Ile Leu Glu Glu Ala Ser Gly Gly Ala450 455 460Gly Gly Gly Ala Gly Arg Leu Gln Glu Leu Gly Pro Gly Val Val Ser465 470 475 480Gly Ser Gly Val Val Pro Trp Val Val Ser Ala Arg Ser Glu Leu Ala485 490 495Leu Arg Gly Gln Ala Arg Arg Leu Arg Gly Val Val Ala Val Gly Gly500 505 510Gly Ala Asp Gly Val Gly Val Ser Pro Ala Gly Val Gly Arg Ala Leu515 520 525Val Ser Glu Arg Ser Val Phe Glu His Arg Ala Val Val Val Ala Glu530 535 540Asp Arg Asp Glu Phe Leu His Ala Leu Asp Ala Leu Ala Gly Gly Arg545 550 555 560Pro Val Pro Gly Val Val Glu Gly Arg Thr Thr Ser Gly Glu Leu Ala
565 570 575Val Leu Phe Ala Gly Gln Gly Thr Gln Arg Ala Gly Met Gly Arg Glu580 585 590Leu Tyr Glu Ala Tyr Pro Val Phe Ala Gln Ala Ile Asp Glu Ile Cys595 600 605Ala Glu Ala Asp Thr Ala Arg Thr Asp Pro Gly Ala Pro Gly Leu Arg610 615 620Asp Val Leu Phe Ala Pro Gln Asp Ser Pro Glu Gly Arg Leu Ile Glu625 630 635 640Asp Thr Gly Phe Ala Gln Pro Ala Leu Phe Ala Phe Glu Val Ala Leu645 650 655Phe Arg Leu Leu Glu Thr Trp Gly Leu Thr Pro Asp Tyr Val Leu Gly660 665 670His Ser Val Gly Glu Leu Ala Ala Ala His Val Ala Gly Met Leu Cys675 680 685Leu Ala Asp Ala Val Ala Leu Val Val Ala Arg Gly Arg Leu Met Gln690 695 700Gly Leu Pro Ser Gly Gly Ala Met Val Ala Ile Glu Ala Ser Glu Asp705 710 715 720Glu Ile Leu Pro Leu Pro Asp Glu Tyr Ala Ser Arg Val Ala His Ala725 730 735Ala Val Asn Gly Pro Arg Ser Ile Val Leu Ser Gly Asp Glu Asp Ala740 745 750Val Leu Asp Leu Ala Gln Gln Trp Ala Ala Arg Gly Arg Arg Thr Arg755 760 765Arg Leu Arg Thr Ser His Ala Phe His Ser Pro His Met Asp Ala Met770 775 780Leu Gly Asp Phe Arg Arg Ala Ala Glu Gln Val Thr Phe Ser Ala Pro785 790 795 800Arg Ile Pro Val Val Ser Asn Val Thr Gly Ala Pro Leu Pro Ala Glu805 810 815Thr Met Cys Thr Pro Asp Tyr Trp Val Glu His Ala Arg Ser Thr Val820 825 830Arg Phe Ala Asp Gly Ile Ser Trp Leu Gln Glu Gln Gly Val Thr Thr835 840 845Cys Leu Glu Ile Gly Pro Asp Gly Thr Leu Ser Ala Leu Ala Gln Asp850 855 860Ser Leu Ser Ala Pro Ala Arg Ala Ile Pro Ala Leu Arg Pro Asp Gln865 870 875 880Pro Glu Ala Arg Ser Val Met Thr Ala Leu Ala Glu Leu Phe Val Ala885 890 895Gly Thr Ala Val Glu Trp Ala Gly Val Phe Glu Gly Thr Ala Arg Glu900 905 910Val Gly Asp Gly Cys Gly Val Glu Leu Pro Thr Tyr Ala Phe Glu Arg915 920 925Glu Arg Phe Trp Leu Asp Val Glu Glu Gly Ser Ala Gly Gly Ser Gly930 935 940Val Ser Gly Met Trp Gly Gly Pro Leu Trp Glu Ala Val Glu Cys Gly945 950 955 960Asp Ala Gly Val Val Ala Ser Leu Leu Gly Val Asp Glu Gly Ala Ser965 970 975Leu Gly Ala Val Val Ser Ala Leu Gly Glu Trp Gly Arg Val Arg His980 985 990Glu Arg Glu Val Val Asp Gly Trp Arg Tyr Arg Glu Val Trp Arg Pro99510001005Val Ser Gly Gly Gly Val Gly Gly Leu Ser Gly Ala Trp Leu Val Val101010151020Ser Glu Gly Glu Ala Gly Pro Val Asp Val Val Ala Glu Gly Leu Glu1025 103010351040Arg Cys Gly Ala Arg Val Val Arg Val Glu Val Glu Ala Gly Cys Val104510501055Ser Arg Glu Val Leu Ala Gly His Leu Arg Glu Ala Val Asp Gly Glu106010651070Ala Val Gly Gly Val Val Ser Leu Val Gly Trp Gly Ser Gly Val Val107510801085Gln Ala Gly Val Ala Ser Val Gly Leu Val Gln Ala Leu Gly Asp Val109010951100Gly Val Gly Ala Arg Leu Trp Cys Val Thr Gly Gly Ala Val Ser Val1105 111011151120Gly Gly Arg Asp Ala Val Trp Gly Pro Ala Ser Gly Val Val Trp Gly112511301135Leu Gly Arg Val Val Gly Ala Glu Ala Pro Asp Arg Trp Gly Gly Leu114011451150Val Asp Val Pro Glu Leu Val Asp Glu Arg Val Val Asp Gly Leu Val115511601165Gly Val Leu Ala Gly Val Gly Gly Gly Gly Glu Ser Glu Phe Ala Val117011751180Arg Ser Ser Gly Ala Phe Val Arg Arg Leu Val Arg Ala Pro Leu Glu1185 119011951200Glu Ala Val Ala Glu Arg Glu Trp Arg Pro Arg Gly Thr Val Leu Val120512101215Thr Gly Gly Thr Gly Glu Leu Gly Ala His Val Ala Arg Trp Met Ala122012251230Arg Arg Gly Ala Glu His Leu Leu Leu Val Ser Arg Arg Gly Glu Ser123512401245Ala Gln Gly Val Glu Glu Leu Arg Ala Asp Leu Met Gly Leu Gly Ala125012551260Arg Val Ser Val Val Ala Cys Asp Ala Ala Asp Arg Glu Ala Leu Ala1265 127012751280Glu Val Leu Arg Ser Ala Val Pro Ala Glu Cys Pro Leu Gly Val Val128512901295Val His Ala Ala Gly Val Val Asp Asp Gly Val Leu Glu Gly Leu Ser130013051310Ser Glu Arg Val Thr Gly Val Leu Arg Ala Lys Ala Leu Ala Ala Trp131513201325Asn Leu His Glu Leu Thr Arg Gly Ala Asp Leu Ser Gly Phe Val Val133013351340Phe Ser Ser Ala Ala Ala Thr Phe Gly Pro Ala Gly Gln Gly Ser Tyr1345 135013551360Ala Ala Ala Asn Ala Tyr Val Glu Ala Ile Val Arg His Arg Arg Gly136513701375Glu Gly Leu Pro Gly Leu Ala Val Ala Trp Gly Pro Trp Ala Gly Gly138013851390Gly Met Ala Glu Gly Ala Val Gly Gln Met Arg Arg Arg Gly Leu Ala139514001405Ala Met Thr Pro Glu Thr Ala Leu Val Ala Leu Gly Gln Ala Leu Asp141014151420His Asp Glu Thr Cys Val Thr Val Ala Asp Ile Asp Trp Asp Arg Phe1425 143014351440Thr Ala Asn Ser Leu Pro Gly Ser Arg Leu Ser Pro Leu Ile Ser Asp144514501455Ile Pro Glu Ala Arg Leu Ala Arg Glu Thr Thr Gly Leu Asp Thr Ala146014651470Thr Ala Ser Pro Asp Ser Phe Ser Ala Arg Leu Lys Ala Met Asp Thr147514801485Ala Glu Gln Glu Arg Ala Leu Leu Asp Leu Val Arg Thr Tyr Ala Ala149014951500Thr Val Leu Gly His Ser Thr Pro Thr Ala Val Arg Pro Glu Arg Ala1505 151015151520Phe Arg Asp Leu Gly Phe Val Ser Val Ser Ala Val Glu Leu Arg Asn152515301535Arg Leu Asn Ala Val Thr Gly Leu Leu Leu Pro Thr Thr Leu Ile Phe154015451550Asp Tyr Pro Thr Pro Ser Ala Leu Ala Gly Tyr Leu Lys Glu Gln Leu155515601565Glu Glu Gly Ala Gly Gly Gln Arg Asp Ile Ala Pro Pro Val Pro Ala157015751580Ser Arg Val Asp Val Asp Glu Pro Ile Ala Ile Val Gly Met Ala Cys1585 159015951600Arg Phe Pro Gly Gly Val Glu Ser Ala Glu Asp Leu Trp Glu Leu Val160516101615Ala Ser Gly Arg Asp Ala Val Gly Glu Phe Pro Val Asp Arg Gly Trp162016251630Asp Val Glu Ala Phe Tyr Asp Pro Glu Pro Gly Arg Ala Gly Ser Ser163516401645Tyr Thr Arg Arg Gly Gly Phe Leu Glu Gly Ala Ala Glu Phe Asp Ala165016551660Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln1665 167016751680Gln Arg Leu Met Leu Glu Val Ser Trp Glu Ala Leu Glu Arg Ala Gly168516901695Ile Asp Pro Ala Thr Leu Arg Gly Ser Thr Thr Gly Val Phe Ala Gly170017051710Met Cys Ser Gln Asp Tyr Ala Asp Leu Val Arg Arg Ala Thr Glu Asp171517201725Leu Glu Gly Tyr Ala Met Thr Gly Leu Ser Ser Ser Val Thr Ser Gly173017351740Arg Val Ala Tyr Thr Leu Gly Leu Glu Gly Pro Ala Val Thr Val Asp1745 175017551760Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys Gln Ala176517701775Leu Arg Ser Gly Glu Cys Ser Leu Ala Leu Ala Gly Gly Val Thr Val178017851790Met Ser Thr Pro Gly Ala Phe Val Glu Phe Ser Arg Gln Arg Gly Leu179518001805Ser Pro Asp Gly Arg Cys Lys Ala Tyr Gly Ser Gly Ala Asp Gly Val181018151820Gly Trp Ala Glu Gly Val Gly Val Leu Leu Val Glu Arg Leu Ser Glu1825 183018351840Ala Glu Arg Arg Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala184518501855Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro186018651870Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Cys Ala Gly Leu Ser187518801885Val Ala Asp Val Asp Val Val Glu Gly His Gly Thr Gly Thr Thr Leu189018951900Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Gly1905 191019151920Arg Ser Gly Glu Arg Pro Val Trp Leu Gly Ser Val Lys Ser Asn Ile192519301935Gly His Ala Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val194019451950Met Ala Leu Arg Ala Gly Val Leu Pro Arg Thr Leu His Val Asp Glu195519601965Pro Ser Ser Gln Val Asp Trp Ser Ser Gly Ser Val Arg Val Leu Ala197019751980Asp Glu Val Glu Trp Pro Gly Val Glu Gly Arg Leu Arg Arg Ala Gly1985 199019952000Val Ser Ala Phe Gly Val Ser Gly Thr Asn Ala His Val Ile Leu Glu200520102015Glu Ala Ser Gly Gly Ala Asp Gly Gly Ala Gly Arg Leu Gln Glu Leu202020252030Gly Pro Gly Val Val Ser Gly Ser Gly Val Val Pro Trp Val Val Ser203520402045Ala Arg Ser Glu Leu Ala Leu Arg Gly Gln Ala Arg Arg Leu Arg Gly205020552060Val Val Ala Val Gly Gly Gly Ala Asp Gly Val Gly Val Ser Pro Ala2065 207020752080Gly Val Gly Arg Ala Leu Val Ser Glu Arg Ser Val Phe Glu His Arg208520902095Ala Val Val Val Ala Glu Asp Arg Asp Glu Phe Leu His Ala Leu Asp210021052110Ala Leu Ala Glu Gly Ala Pro Thr Ala Gly Val Val Gln Gly Val Ala211521202125Gly Pro Ala Ala Asp Gly Lys Ile Ala Met Leu Phe Gly Gly Gln Gly213021352140Thr His Trp Glu Gly Met Ala Gln Glu Leu Leu Gly Ser Ser Pro Val2145 215021552160Phe Ala Gln Gln Met Ser Asp Cys Ala Gln Ala Leu Glu Pro Tyr Leu216521702175Asp Trp Ser Leu Leu Asp Val Leu Arg Gly Ala Pro Asp Ala Pro Pro218021852190Leu Gln Arg Val Asp Val Val Gln Pro Val Leu Phe Ala Val Met Val219522002205Ser Leu Ala Ala Leu Trp Arg Ser Tyr Gly Val His Pro Asp Ala Val221022152220Ala Gly His Ser Gln Gly Glu Ile Ala Ala Ala Tyr Val Ala Gly Ala2225 223022352240Leu Ser Leu Asp Asp Ala Ala Arg Val Thr Ala Leu Arg Ser Gln Ala224522502255Leu Ala Ala Leu Ala Gly Gln Gly Ala Met Ala Ser Val Gly Leu Pro226022652270Val Glu Lys Leu Glu Pro Arg Leu Ala Thr Trp Gly Asp Arg Leu Val227522802285Ile Ala Ala Val Asn Gly Ala Arg Ser Ala Val Val Ser Gly Glu Pro229022952300Glu Ala Val Asp Ala Leu Val Glu Glu Leu Ser His Glu Asp Val Pro2305 231023152320Ala Arg Arg Leu Met Val Asp Trp Ala Ser His Ser Pro Gln Val Glu232523302335Ala Ile Gln Gly Arg Leu Leu Glu Leu Leu Ala Pro Ile Arg Ala Arg234023452350Thr Gly Asp Val Pro Phe Tyr Ser Thr Val Thr Gly Glu Arg Ile Asp235523602365Gly Thr Glu Leu Asp Ala Asp Tyr Trp Tyr Arg Asn Leu Arg Gln Val237023752380Val Arg Phe Arg Asp Ala Thr Gln Ala Leu Val Arg Ala Gly His Thr2385 239023952400Val Phe Ile Glu Ala Cys Pro His Pro Ala Val Ala Val Gly Val Gln240524102415Glu Thr Leu Asp Glu Met Gly Asp Leu Asp Ser Leu Val Val Gly Ser242024252430Leu Arg Arg Gly Glu Gly Gly Leu Arg Arg Phe Leu Met Ser Val Ala243524402445Glu Leu Phe Val Gly Gly Val Ala Val Glu Trp Ser Gly Val Phe Gly245024552460Ser Val Gly Arg Gly Val Ala Gly Gly Cys Gly Val Glu Leu Pro Thr2465 247024752480Tyr Ala Phe Glu Arg Glu Arg Phe Trp Leu Asp Val Glu Gly Ala Pro248524902495Arg Gly Ser Gly Val Ser Gly Gln Trp Gly Gly Gln Leu Ser Glu Ala250025052510Val Asp Thr Val Arg Gly Gly Met Leu Arg Asp Cys Leu Ala Gly Leu251525202525Asp Pro Ala Ala Gln Ala Glu Thr Val Leu Asp Leu Val Leu Thr His253025352540Ala Ala Ala Val Leu Gly His Gly Thr Ala Asp Ala Val Val Pro Glu2545 255025552560Arg Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu256525702575Arg Asn Arg Leu Asn Thr Ala Thr Gly Leu Arg Phe Pro Arg Thr Leu258025852590Val Phe Asp His Pro Arg Pro Val Ala Leu Ala Ala His Ile His Glu259526002605Gln Leu Ser Gly Gly Ser Pro Thr Thr Gly Thr Ala Leu Ala Leu Ala261026152620Leu Arg Ala Pro Ala Pro Arg Val Asp Val Asp Glu Pro Ile Ala Ile2625 263026352640Val Gly Met Ala Cys Arg Phe Pro Gly Gly Val Glu Ser Ala Glu Asp264526502655Phe Trp Glu Leu Ile Ala Ser Gly Arg Asp Ala Val Gly Glu Phe Pro266026652670Val Asp Arg Gly Trp Asp Val Glu Ala 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267526802685Arg Ala Gly Thr Ser Tyr Thr Arg Cys Gly Gly Phe Leu Gln Gly Ala269026952700Ala Glu Phe Asp Ala Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu2705 271027152720Ala Met Asp Pro Gln Gln Arg Leu Met Leu Glu Val Ser Trp Glu Ala272527302735Leu Glu Arg Ala Gly Ile Asp Pro Ala Thr Leu His Gly Ser Thr Thr274027452750Gly Val Phe Ala Gly Val Ser Gln Gln Asp Tyr Ala Glu Leu Leu Arg275527602765Arg Gly Thr Gln Asp His Glu Gly Tyr Ala Leu Thr Gly Val Ser Asn277027752780Ser Val Val Ser Gly Arg Leu Ser Tyr Thr Phe Gly Phe Glu Gly Pro2785 279027952800Ala Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His280528102815Leu Ala Cys Gln Ala Leu Arg Ser Gly Glu Cys Ser Leu Ala Leu Ala282028252830Gly Gly Val Thr Val Met Ser Thr Pro Gly Ala Phe Val Glu Phe Ser283528402845Arg Gln Arg Gly Leu Ser Pro Asp Gly Arg Cys Lys Ala Tyr Gly Ser285028552860Gly Ala Asp Gly Val Gly Trp Ala Glu Gly Val Gly Val Leu Leu Val2865 287028752880Glu Arg Leu Ser Glu Ala Glu Arg Arg Gly His Arg Val Leu Ala Val288528902895Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr290029052910Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala291529202925Cys Ala Gly Leu Ser Val Ala Asp Val Asp Val Val Glu Gly His Gly293029352940Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala2945 295029552960Thr Tyr Gly Gln Gly Arg Ser Gly Glu Arg Pro Val Trp Leu Gly Ser296529702975Val Lys Ser Asn Ile Gly His Ala Gln Ala Ala Ala Gly Val Ala Gly298029852990Val Ile Lys Met Val Met Ala Leu Asn His Glu Leu Leu Pro Thr Ser299530003005Leu His Ile Asp Glu Pro Ser Pro His Ile Asp Trp Ser Ser Gly Gly301030153020Val Arg Leu Leu Thr Glu Pro Val Pro Trp Gln Gln Asn Gly Arg Pro3025 303030353040Arg Arg Ala Gly Val Ser Ala Phe Gly Val Ser Gly Thr Asn Ala His304530503055Val Ile Ile Glu Gln Ala Pro Val Glu Ala His Val Ile Ser Glu Pro306030653070Val Pro Ala Glu Ala His Val Ile Val Glu Gln Ala Pro Val Glu Ala307530803085Pro His Val Val Asp Ala Thr Gly Pro Ala Asp Leu Thr Glu Pro Gln309030953100Glu Glu Ala Ala Glu Pro Glu Cys Val Ala Asp Ala Val Thr Glu Met3105 311031153120Ser Ala Glu Pro Glu Cys Val Ala Asp Ala Met Ser Glu Met Ser Ala312531303135Glu Cys Val Ala Glu Ala Val Ser Asp Lys Ser Ala Glu Pro Glu Cys314031453150Val Ala Asp Ala Met Ser Asp Lys Pro Ala Leu Leu Pro Ile Pro Trp315531603165Leu Leu Ser Ala Lys Ser Glu Arg Ala Leu Arg Gly Gln Ala Arg Arg317031753180Leu Arg Gln Phe Ala Ala Arg Ala Ser Asp Ala Arg Pro Ala Asp Val3185 319031953200Ala His Ala Leu Ala Ala Gln Arg Ser Val Phe Asp His Arg Ala Val320532103215Val Val Ala Glu Asp Arg Asp Gly Phe Leu Gln Ala Leu Asp Ala Leu322032253230Ala Glu Gly Arg Ser Ala Asp Gly Leu Ile Glu Gly Ser Val Gly Pro323532403245Arg Gly Gly His Ser Gly Arg Arg Arg Gly Lys Thr Ala Met Leu Phe325032553260Ala Gly Gln Gly Thr Gln Arg Val Gly Met Gly Arg Gln Leu Tyr Ala3265 327032753280Ala His Pro Ala Tyr Ala Asp Ala Leu Asp Gln Val Leu Ala Glu Leu328532903295Asp Gly His Leu Asp Gln Pro Leu Arg Pro Leu Ile His Ala Ser Ala330033053310Asp Leu Ala Asp Val Ala Asp Ala Ala Asp Val Leu Asp Arg Thr Arg331533203325Tyr Ala Gln Pro Ala Leu Phe Ala Val Gln Val Ala Leu Phe Arg His333033353340Leu Glu Arg Leu Gly Val Arg Ala Asp Phe Val Ala Gly His Ser Ile3345 335033553360Gly Glu Leu Ala Ala Ala His Val Ala Gly Val Leu Pro Leu Ala Ala336533703375Ala Cys Arg Leu Val Ala Ala Arg Gly Arg Leu Met Glu Gln Leu Ala338033853390Pro Gly Gly Ala Met Val Ala Val Arg Ala Ser Glu Ala Glu Ala Arg3395 3400 3405Gln Ala Leu Asp Gly Arg Glu Ala Arg Val Ser Val Ala Ala Val Asn341034153420Gly Pro Ala Ser Val Val Phe Ser Gly Ala Glu Asp Glu Val Gly Asn3425 343034353440Met Ala Asp Trp Phe Ala Glu Arg Gly Arg Arg Val Lys Arg Leu Arg344534503455Thr Gly His Ala Phe His Ser Pro Leu Met Asp Pro Met Leu Glu Glu346034653470Phe Gln Gln Val Ala Ala Ser Leu Thr Tyr Ser Glu Pro Ala Ile Pro347534803485Met Val Ser Thr Leu Thr Gly Asp Ile Val Ala Ala Gly Glu Leu Ser349034953500Asp Pro Glu Tyr Trp Val Arg Gln Val Arg Arg Thr Val Arg Phe Gly3505 351035153520Asp Ala Ile Ser Arg Leu His Thr Asp Gly Val Arg Thr Phe Met Glu352535303535Leu Gly Pro Asp Gly Thr Leu Ser Ala Leu Ala Glu Glu Cys Leu Glu354035453550Ala Thr Ala Asp Ser His Pro Ala Asp Asp Asp Thr Gly Thr Pro Gln355535603565Glu Asn Leu Leu Ile Pro Leu Leu Arg Pro Asp Ser Pro Glu Pro Gly357035753580Thr Leu Leu Thr Gly Leu Ala Arg Leu His Thr His Gly Ala Ala Ala3585 359035953600Val Asn Trp Pro Ala Ala Leu Pro Glu Arg Asp Arg Ala Arg His Leu360536103615Asp Leu Pro Thr Tyr Ala Phe Asp His His Arg Tyr Trp Val Asp Thr
362036253630Ser Ala Gly His Pro Gly Asp Leu Ser Ala Ala Gly Leu Gly Thr Ala363536403645Gly His Pro Leu Leu Gly Ser Ala Val Ala Leu Ala Glu Ser Gln Glu365036553660Leu Leu Phe Thr Gly Arg Leu Ser Leu Arg Thr His Pro Trp Leu Ala3665 367036753680Asp His Ala Ile Phe Gly Thr Val Leu Leu Pro Gly Thr Ala Ile Leu368536903695Glu Leu Ala Val Arg Ala Gly Asp Glu Val Asp Cys Gly Thr Val Glu370037053710Glu Leu Thr Leu Arg Thr Pro Leu Val Leu Pro Glu Gln Gly Ser Val371537203725Ile Leu Gln Leu Ser Val Gly Ala Pro Gln Gly Pro Gln Thr Pro Glu373037353740Glu Pro Glu Arg Arg Thr Phe Ala Leu Tyr Ala Arg Glu Asp Asp Gly3745 375037553760Leu Ser Ser Ser Ser Ala Ala Ala Thr Gly Thr Glu Trp Thr Cys His376537703775Ala Thr Gly Val Leu Thr Gly Thr Ala Arg Pro Ala Glu Glu His Thr378037853790Gln Glu Pro Trp Pro Pro Ala Asp Ala Ala Pro Val Asp Leu Asp Gly379538003805Trp Tyr Glu Gln Leu Ala Gly Ala Gly Leu Gly Tyr Gly Pro Val Phe381038153820Gln Gly Leu Arg Glu Val Trp Arg Arg Gly Asp Glu Val Phe Ala Val3825 383038353840Val Thr Leu Pro Glu Ser Thr Glu Gly Gln Ala Ala Asp Ala Ala Arg384538503855Tyr Ala Leu His Pro Ala Leu Leu Asp Ala Ala Leu His Pro Val Val386038653870Leu Arg His Glu Gly Asp Ala Ala Ala Asp Gly His Gly Trp Leu Pro387538803885Phe Ser Trp Thr Gly Val Thr Val Ala Ala Ser Gly Ala Ser Thr Leu389038953900His Val Arg Leu Thr Val Arg Thr Asp Glu Asp Ala Val Gly Leu Leu3905 391039153920Ala Thr Asp Ala Ser Gly Arg Ile Val Ile Ser Ala Gly Ser Leu Ala39253930 3935Phe Arg Pro Val Ser Ala Glu Gln Leu Gln Ala Ala Arg Thr Gly Tyr394039453950His Asp His Leu Phe Arg Ile Glu Trp Arg Pro Leu His Leu Pro Thr395539603965Thr Pro Ala Arg Thr Ala Asp Trp Ala Leu Ile Gly Pro Gly Ala Arg397039753980Arg Thr Ala Ala Val Leu Glu Arg Asn Gly Ala Ser Trp Gln Ala Tyr3985 399039954000Pro Asp Pro Ala Ala Leu Ala Glu Ala Leu Ala Ala Gly Ala Pro Ala400540104015Pro Gly Met Val Val Ile Ser Cys Glu Pro Asp Gly Ala Ser Ala Pro402040254030Thr Asp Ser Ala Leu Thr Asp Ser Ala Leu Thr Asp Ser Ala Pro Ala403540404045Gly Ser Ala Pro Ala Asp Ser Thr Ala Leu Ala Asp Ala Thr Arg Gln405040554060Ala Thr Thr Arg Val Leu Ala Leu Leu Gln Glu Trp Val Ala Asp Glu4065 407040754080Arg Leu Ala Ala Cys Arg Leu Ala Leu Leu Thr His Gly Ser Val Thr408540904095Ala Thr Pro Asp Glu Pro Val Ser Asp Leu Ala His Ala Ala Val Trp410041054110Gly Leu Val Arg Ser Val Gln Thr Glu Asn Pro Asp Arg Phe Leu Leu411541204125Ala Asp Thr Asp Asp Thr Asp Ala Ser Arg Asn Ala Leu Pro Leu Leu413041354140Ala Gly Glu Pro Gln Ile Ala Leu Arg Asn Gly Ala Val Arg Ile Pro4145 415041554160Arg Met Thr Arg Val Pro Val Arg Gln Pro Gln Pro Ser Thr Thr Asp416541704175Ala Asp Trp Asp Pro Glu Ala Thr Val Leu Ile Thr Gly Gly Thr Gly418041854190Val Leu Gly Arg Leu Val Ala Arg His Leu Ala Thr Ala His Gly Val419542004205Arg His Leu Leu Leu Ala Thr Arg Arg Gly Thr Ala Ala Asp Gly Ala421042154220Ala Asp Leu Val Ala Glu Leu Ala Gly Leu Gly Ala Glu Ala Thr Val4225 423042354240Ala Ala Cys Asp Ile Gly Asp Arg Ala Ala Val Ala Ala Leu Leu Asp424542504255Gln Val Pro Ala Gln His Pro Leu Lys Ala Val Ile His Thr Ala Gly426042654270Val Val Asp Asp Gly Ile Leu Thr Ser Leu Thr Pro Glu Arg Met Glu427542804285Ala Val Leu His Ala Lys Ala Phe Gly Ala Ala His Leu His Asp Leu429042954300Thr Arg Asp Ala Gly Leu Thr Thr Phe Thr Val Phe Ser Ser Ala Ala4305 431043154320Ala Ser Phe Gly Ser Pro Gly Gln Gly Asn Tyr Thr Ala Ala Asn Ala
432543304335Phe Leu Asp Ala Leu Met Gln His Arg His Thr Gln Ala Leu Pro Gly434043454350Arg Ser Leu Ala Trp Gly Leu Trp Gly Glu Ala Asp Gly Met Thr Arg435543604365Asn Leu Ala Gly Thr Asp Phe Ala Arg Met Ala Arg Gly Gly Leu Leu437043754380Pro Leu Ser Asn Ala Gln Gly Leu Ala Leu Leu Asp Thr Ala Asp Arg4385 439043954400Leu Gly Pro Phe Gly Asp Gly Leu Leu Leu Ala Thr Arg Leu Asp Ala440544104415Ala Thr Leu His Ala Gln Ala Thr Ala Gly Ala Leu Pro Arg Ile Leu442044254430His Gly Leu Ile Arg Ile Pro Ala Arg Arg Ser Ala Asp His Gly Ile443544404445Ala Thr Asp Thr Pro Ala Thr Leu Arg Glu Arg Leu Ala Gly Leu Thr445044554460Ile Pro Ala Gln Arg Thr Gly Leu Leu Leu Glu Leu Val Arg Thr His4465 447044754480Ala Ala Ala Val Leu Gly His Pro Tbr Ser Ala Val Thr Ala Ala Asp448544904495Gly Ala Leu Pro Asp Asp Leu Val Pro Ala Asp Thr Glu Phe Arg Asp450045054510Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu Arg Asn Arg Ile Asn451545204525Ala Val Thr Gly Leu Arg Leu Pro Ala Thr Leu Ile Phe Asp Gln Pro453045354540Ser Pro Ala Ala Leu Ala Asp His Leu Ala Thr Arg Leu Thr Ala Glu4545 455045554560Ala Gly Thr Pro Asp Glu Pro Ala Pro Ala Ala Ala Ala Ala Gly Ala456545704575Gly Ser Ala Gly Ser Ala Glu Thr Gly Gln Gln Arg Ser Thr Gly Ser45804585 4590Glu Lys Gln Gln Thr Arg Gly Gly Thr Ser Thr Glu Thr Val Glu Ser459546004605Leu Phe Trp Ile Gly His Asp Thr Arg Arg Ile Glu Glu Ser Met Ala461046154620Leu Leu Ser Ala Ala Ser Phe Phe Arg Pro Ala Phe Thr Asp Pro Ser4625 463046354640Asp Ile Pro Glu Pro Thr Phe Val Arg Leu Ala Gln Gly Glu Ala Arg464546504655Ala Gln Gly Glu Ala Leu Ala Arg Gly Glu Thr Arg Pro Ala Leu Ile466046654670Cys Leu Pro Thr Val Ala Ala Val Ser Ser Val Tyr Gln Tyr Ser Arg467546804685Phe Ala Ala Gly Leu Asn Gly His Arg Asp Val Trp Tyr Val Pro Ala469046954700Pro Gly Phe Leu Glu Gly Glu Pro Leu Pro Ser Gly Ile Gly Ala Val4705 471047154720Thr Arg Met Phe Ala Asp Ala Ile Val Arg Phe Thr Asp Gly Ala Pro472547304735Phe Ala Leu Ala Gly His Ser Ala Gly Gly Trp Phe Val Tyr Ala Val474047454750Thr Ser His Leu Glu Arg Leu Gly Val Arg Pro Glu Ala Val Val Thr475547604765Met Asp Ala Tyr Leu Pro Asp Asp Gly Ile Ala Pro Val Ala Ser Ala477047754780Leu Thr Ser Glu Ile Phe Asp Arg Val Thr Gln Phe Val Asp Val Asp4785 479047954800Tyr Thr Arg Leu Val Ala Met Gly Gly Tyr Phe Arg Ile Phe Ser Gly480548104815Trp Ser Pro Pro Asp Ile Thr Thr Pro Ala Leu Phe Leu Arg Gly Arg482048254830Asp Gly Glu Gln Met Pro Pro Pro Trp Gly Val Pro His Thr Val Leu483548404845Asp Ile Gln Gly Asn His Phe Thr Met Leu Glu Gln Phe Ala Asp Ser485048554860Thr Ala Arg His Val Asp Glu Trp Leu Thr Glu Ile Ala Ser Val Arg4865 487048754880Arg<210>6<211>5532<212>PRT<213>除蟲鏈霉菌<400>6Met Asp Thr Ser Ser Glu Lys Leu Val Asp Ala Leu Arg Ala Ser Leu1 5 10 15Lys Ala Asn Gln Thr Leu Arg Ala Arg Asn Glu Gln Leu Ala Ala Ala20 25 30Met Glu Ala Ser Ser Glu Pro Ile Ala Ile Val Gly Met Ala Cys Arg35 40 45Phe Pro Gly Gly Val Cys Ser Pro Glu Glu Leu Trp Glu Leu Val Ala50 55 60Ser Gly Gly Asp Ala Ile Gly Glu Phe Pro Ala Gly Arg Gly Trp Asp65 70 75 80Leu Glu Gly Leu Phe Asp Ser Asp Pro Asp Arg Ser Gly Thr Ser Tyr85 90 95Ala Arg Tyr Gly Gly Phe Leu Tyr Glu Ala Gly Glu Phe Asp Ala Asp
100105 110Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln115 120 125Arg Leu Leu Leu Glu Thr Ser Trp Glu Ala Phe Glu Arg Ala Gly Ile130 135 140Asp Pro Leu Ser Met Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Val145 150 155 160Met Tyr His Asp Tyr Gly Ser Arg Leu Gly Thr Ile Pro Glu Gly Phe165 170 175Glu Gly Tyr Ile Gly Asn Gly Ser Gly Gly Ala Val Ala Ser Gly Arg180 185 190Val Ala Tyr Thr Leu Gly Leu Glu Gly Pro Ala Val Ser Val Asp Thr195 200 205Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys Gln Ser Leu210 215 220Arg Ser Gly Glu Cys Thr Leu Ala Leu Ala Gly Gly Val Thr Val Met225 230 235 240Ser Thr Pro His Leu Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ser245 250 255Val Asp Gly Arg Cys Lys Ser Phe Ala Gly Gly Ala Asp Gly Thr Gly260 265 270Met Gly Glu Gly Val Gly Met Leu Leu Val Glu Arg Leu Ser Asp Ala275 280 285Val Arg Leu Gly His Arg Val Leu Ala Val Leu Arg Gly Ser Ala Val290 295 300Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ala305 310 315 320Gln Glu Arg Val Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Ser Val325 330 335Ala Asp Val Asp Val Val Glu Gly His Gly Thr Gly Thr Thr Leu Gly340 345 350Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Arg Ala355 360 365Gly Asn Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His370 375 380Ala Gln Ala Ala Ala Gly Val Gly Gly Val Ile Lys Met Val Met Ala385 390 395 400Leu Arg Glu Gly Val Leu Pro Arg Thr Leu His Val Asp Glu Pro Ser405 410 415Pro Gln Val Asp Trp Ser Ala Gly Ala Val Arg Leu Leu Thr Glu Ala420 425 430Val Pro Trp Pro Gly Asp Ala Ala Gly Arg Leu Arg Arg Ala Gly Val435 440 445Ser Ser Phe Gly Val Ser Gly Thr Asn Ala His Val Ile Leu Glu Glu450 455 460Ala Pro Ala Ala Gly Gly Cys Val Ala Gly Gly Gly Val Leu Glu Gly465 470 475 480Ala Pro Gly Leu Ala Ile Ser Val Ala Glu Ser Val Ala Ala Pro Val485 490 495Ala Val Ser Ala Pro Val Ala Glu Ser Val Pro Val Pro Val Pro Val500 505 510Pro Val Pro Val Pro Val Ser Ala Arg Ser Glu Ala Gly Leu Arg Ala515 520 525Gln Ala Glu Ala Leu Arg Gln Tyr Val Ala Val Arg Pro Asp Val Ser530 535 540Leu Ala Asp Val Gly Ala Gly Leu Ala Cys Gly Arg Ala Val Leu Glu545 550 555 560His Arg Ala Val Val Leu Ala Ala Asp Arg Glu Glu Leu Val Gln Gly565 570 575Leu Gly Ala Leu Ala Ala Gly Glu Pro Asp Arg Arg Val Thr Thr Gly580 585 590His Ala Pro Gly Gly Asp Arg Gly Gly Val Val Phe Val Phe Pro Gly595 600 605Gln Gly Gly Gln Trp Ala Gly Met Gly Val Arg Leu Leu Ala Ser Ser610 615 620Pro Val Phe Ala Arg Arg Met Gln Ala Cys Glu Glu Ala Leu Ala Pro625 630 635 640Trp Val Asp Trp Ser Val Val Asp Ile Leu Arg Arg Asp Ala Gly Asp645 650 655Ala Val Trp Glu Arg Ala Asp Val Val Gln Pro Val Leu Phe Ser Val660 665 670Met Val Ser Leu Ala Ala Leu Trp Arg Ser Tyr Gly Ile Glu Pro Asp675 680 685Ala Val Leu Gly His Ser Gln Gly Glu Ile Ala Ala Ala His Val Cys690 695 700Gly Ala Leu Ser Leu Lys Asp Ala Ala Lys Thr Val Ala Leu Arg Ser705 710 715 720Arg Ala Leu Ala Ala Val Arg Gly Arg Gly Gly Met Ala Ser Val Pro725 730 735Leu Pro Ala Gln Glu Val Glu Gln Leu Ile Gly Glu Arg Trp Ala Gly740 745 750Arg Leu Trp Val Ala Ala Val Asn Gly Pro Arg Ser Thr Ala Val Ser755 760 765Gly Asp Ala Glu Ala Val Asp Glu Val Leu Ala Tyr Cys Ala Gly Thr770 775 780Gly Val Arg Ala Arg Arg Ile Pro Val Asp Tyr Ala Ser His Cys Pro785 790 795 800His Val Gln Pro Leu Arg Glu Glu Leu Leu Glu Leu Leu Gly Asp Ile
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Val Arg Gly Glu Arg Val Leu Ala144514501455Ala Arg Leu Thr Arg Leu Glu Ser Ser Val Asp Val Pro Ala Gln Arg146014651470Ser Gly Asp Val Ala Gly Arg Glu Val Leu Pro Trp Leu Ser Gly Gly147514801485Ser Val Leu Val Thr Gly Gly Thr Gly Val Leu Gly Ala Ala Val Ala149014951500Arg His Leu Ala Gly Val Cys Gly Val Arg Asp Leu Leu Leu Val Ser1505 151015151520Arg Arg Gly Pro Asp Ala Pro Gly Ala Glu Gly Leu Arg Ala Glu Leu1525 15301535Ala Ala Leu Gly Ala Glu Val Arg Ile Val Ala Cys Asp Val Gly Glu154015451550Arg Arg Glu Val Val Arg Leu Leu Glu Gly Val Pro Ala Gly Cys Pro155515601565Leu Thr Gly Val Val His Ala Ala Gly Val Leu Asp Asp Ala Thr Ile157015751580Ala Ser Leu Thr Pro Glu Arg Leu Gly Thr Val Phe Ala Ala Lys Val1585 159015951600Asp Ala Ala Leu Leu Leu Asp Glu Leu Thr Arg Gly Met Glu Leu Ser160516101615Ala Phe Val Leu Phe Ser Ser Ala Ala Gly Ile Leu Gly Ser Ala Gly162016251630Gln Gly Asn Tyr Ala Ala Ala Asn Ala Ala Leu Asp Ala Leu Ala Tyr163516401645Arg Arg Arg Ala Ala Gly Leu Pro Gly Val Ser Leu Ala Trp Gly Leu165016551660Trp Glu Glu Ala Ser Gly Met Thr Gly His Leu Ala Gly Thr Asp His1665 167016751680Arg Arg Ile Ile Arg Ser Gly Leu His Pro Met Ser Thr Pro Asp Ala168516901695Leu Ala Leu Phe Asp Ala Ala Leu Ala Leu Asp Arg Pro Val Leu Leu170017051710Pro Ala Asp Leu Arg Pro Ala Pro Pro Leu Pro Pro Leu Leu Gln Asp171517201725Leu Leu Pro Ala Thr Arg Arg Arg Thr Thr Arg Thr Thr Thr Thr Gly173017351740Gly Ala Asp Asn Gly Ala Gln Leu His Ala Arg Leu Ala Gly Gln Thr1745 175017551760His Glu Gln Gln His Thr Thr Leu Leu Ala Leu Val Arg Ser His Ile176517701775Ala Thr Val Leu Gly His Thr Thr Pro Asp Thr Ile Pro Pro Asp Arg178017851790Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu Arg179518001805Asn Arg Leu Ser Arg Thr Thr Gly Leu Arg Leu Pro Thr Thr Leu Ala181018151820Phe Asp His Pro Asn Pro Thr Thr Leu Thr His His Leu His Thr Gln1825 183018351840Leu Leu Gly Ser Asp Ser Thr Ala Ser Ile Pro Ala Pro Arg Ala Ala184518501855Ala Val Pro Ala Asp Gln Asp Glu Pro Val Ala Ile Ile Gly Met Ala186018651870Cys Arg Tyr Pro Gly Gly Val Thr Ser Ala Glu Glu Leu Trp Glu Leu187518801885Leu Ala Ser Gly Arg Asp Thr Val Gly Glu Phe Pro Thr Asp Arg Gly189018951900Trp Asp Leu Glu Ala Leu Phe Asp Pro Glu Pro Gly Arg Pro Gly Thr1905 191019151920Ser Tyr Thr Arg Cys Gly Ser Phe Leu Tyr Asp Ala Gly Glu Phe Asp192519301935Ala Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro194019451950Gln Gln Arg Leu Leu Leu Glu Ala Ser Trp Glu Ala Met Glu Gln Ala195519601965Gly Ile Asp Pro Thr Thr Val Arg Gly Ser Gln Thr Gly Val Phe Ala197019751980Gly Leu Ile Pro Gln Ala Tyr Gly Pro Arg Leu His Glu Asn Ala Ala1985 1990 1995 2000Ala Asp Thr Glu Gly Tyr Val Leu Thr Gly Thr Ser Gly Ser Val Ala200520102015Ser Gly Arg Ile Ser Tyr Thr Phe Gly Phe Glu Gly Pro Ala Val Ser202020252030Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys203520402045Gln Ala Leu Arg Ala Gly Glu Cys Ser Met Ala Leu Ala Gly Gly Val205020552060Thr Val Met Ser Ser Pro Gly Ala Phe Val Glu Phe Ser Arg Gln 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Thr269026952700Leu Thr Thr Leu Thr His His Asn Leu Pro Asn Thr Pro Thr Thr Thr2705 271027152720Leu Thr Leu Thr His Pro His His His Pro Gln Thr His Leu Leu Thr272527302735Asn Leu Ala Lys Thr Thr Thr Thr Trp His Pro His His Tyr Thr His274027452750His His Asn Gln Pro His Thr His Thr His Leu Asp Leu Pro Thr Tyr275527602765Pro Phe Gln His His His Tyr Trp Leu Glu Ser Thr Gln Pro Gly Ala277027752780Gly Asn Val Ser Ala Ala Gly Leu Asp Pro Thr Glu His Pro Leu Leu2785 279027952800Gly Ala Thr Leu Glu Leu Ala Glu Gly Asp Gly Cys Leu Leu Thr Gly280528102815Arg Leu Ser Leu Arg Thr His Pro Trp Leu Ala Gly His Ala Val Gly282028252830Gly Val Val Leu Leu Pro Gly Thr Ala Phe Ala Glu Leu Ala Leu His283528402845Ala Gly Glu Ser Val Gly Cys Asp His Val Asp Glu Leu Thr Leu His285028552860Thr Pro Leu Val Ile Pro Glu Val Gly Asp Val Thr Leu Gln Val Ala2865 287028752880Ile Ala Ala Pro Asp Glu Ser Gly Arg Arg Met Met Thr Ile His Ser288528902895Arg Gly Glu Gly Gly Ser Gly Gly Ala Asp Ala Ser Ala Ser Ala 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291529202925Ala Ser Tyr Glu Leu Leu Ala Gly Pro Trp Pro Pro Val Gly Ala Thr2930 29352940Pro Val Asp Leu Asn Thr Ala Tyr Asp Gln Met Ala Asp Ala Gly Phe2945 295029552960Ala Tyr Gly Leu Ala Phe Gln Gly Leu Arg Ala Ala Trp Arg Tyr Gly296529702975Asp Asp Ile Leu Val Glu Ala Arg Leu Pro Glu Glu Val Ser Gly Asp298029852990Ala Ala Ala Tyr Gly Leu His Pro Ala Leu Leu Asp Ala Ala Leu Gln299530003005Gly Thr Gly Leu Leu Ser Val Ala Gly Pro Gly Thr Pro Val Val Pro301030153020His Val Trp Asn Gly Leu Arg Phe Arg Thr His Gly Ala Val Ser Val3025 303030353040Arg Ala Cys Leu Ser Thr Leu Gly Ala Thr Gly Ala Ala Val Cys Val304530503055Arg Ile Thr Asp Asp Thr Gly Val Pro Val Ala Ser Val Asp Arg Leu305030653070Glu Leu Arg Pro Val Asp Met Gly Gln Leu Arg Ala Val Ser Val Ser307530803085Ala Gly Arg Arg Gly Ser Leu Tyr Ala Val Gln Trp Ala Glu Val Gly309030953100Pro Val Pro Val Cys Gly Gln Ala Trp Ala Trp His Glu Asp Val Gly3105 311031153120Glu Ser Gly Gly Gly Pro Val Pro Gly Val Val Val Leu Arg Cys Pro312531303135Asp Ala Gly Ala Asp Gly Gly Gly Gly Gly Gly Val Gly Glu Val Val314031453150Gly Gly Val Leu Gly Val Val Gln Gly Trp Leu Gly Leu Glu Arg Phe315531603165Ala Gly Ser Arg Leu Val Val Val Thr Arg Gly Ala Val Val Ala Gly317031753180Pr0 Glu Asp Gly Pro Val Asp Val Val Gly Ala Ala Val Trp Gly Leu3185 319031953200Val Arg Ser Ala Gln Ala Glu His Pro Asp Arg Phe Val Leu Leu Asp320532103215Leu Asp Thr Asp Leu Asp Ser Gly Ala Asp Ala Asp Ala Gly Asn Glu322032253230Ala Gly Met Gly Ser Gly Leu Asp Gly Gly Arg Val Ala Ala Val Val323532403245Ala Cys Gly Glu Pro Gln Leu Ala Val Arg Gly Glu Arg Val Leu Ala325032553260Ala Arg Leu Thr Arg Leu Glu Ser Pro Val Asp Val Ser Gly Arg Glu3265 327032753280Val Leu Pro Trp Leu Ser Gly Gly Ser Val Leu Val Thr Gly Gly Thr328532903295Gly Val Leu Gly Ala Ala Val Ala Arg His Leu Ala Gly Val Cys Gly330033053310Val Arg Asp Leu Leu Leu Val Ser Arg Arg Gly Pro Asp Ala Pro Gly331533203325Ala Glu Gly Leu Arg Ala Glu Leu Ala Ala Leu Gly Ala Glu Val Arg333033353340Ile Val Ala Cys Asp Val Gly Glu Arg Arg Glu Val Val Arg Leu Leu3345 335033553360Glu Gly Val Pro Ala Gly Cys Pro Leu Thr Gly Val Val His Ala Ala336533703375Gly Val Leu Asp Asp Ala Thr Ile Ala Ser Leu Thr Pro Glu Arg Leu338033853390Gly Thr Val Phe Ala Ala Lys Val Asp Ala Ala Leu Leu Leu Asp Glu339534003405Leu Thr Arg Gly Met Glu Leu Ser Ala Phe Val Leu Phe Ser Ser Ala341034153420Ala Gly Ile Leu Gly Ser Ala Gly Gln Gly Asn Tyr Ala Ala Ala Asn3425 343034353440Ala Ala Leu Asp Ala Leu Ala Tyr Arg Arg Arg Ala Ala Gly Leu Pro344534503455Gly Val Ser Leu Ala Trp Gly Leu Trp Glu Glu Ala Ser Gly Met Thr346034653470Gly His Leu Ala Gly Thr Asp His Arg Arg Ile Ile Arg Ser Gly Leu347534803485His Pro Met Ser Thr Pro Asp Ala Leu Ala Leu Phe Asp Ala Ala Leu349034953500Ala Leu Asp Arg Pro Val Leu Leu Pro Ala Asp Leu Arg Pro Ala Pro3505 351035153520Pro Leu Pro Pro Leu Leu Gln Asp Leu Leu Pro Ala Thr Arg Arg Arg352535303535Thr Thr Arg Thr Thr Thr Thr Gly Gly Ala Asp Asn Gly Ala Gln Leu354035453550His Ala Arg Leu Ala Gly Gln Thr His Glu Gln Gln His Thr Thr Leu355535603565Leu Ala Leu Val Arg Ser His Ile Ala Thr Val Leu Gly His Asn Ala357035753580Pro Glu Met Ile Pro Val Asp Ser Ala Phe Arg Asp Leu Gly Phe Asp3585 359035953600Ser Leu Thr Ala Val Glu Leu Arg Asn Arg Leu Gly Glu Ala Thr Gly360536103615Leu Arg Leu Pro Thr Ser Leu Val Phe Asp Gln Pro Asn Ala Ala Thr362036253630Leu Ala Arg His Leu Arg Arg Glu Leu Met Gly Asp Asp Ala Glu Gly363536403645Glu Thr Pro Ser Gln Val Ala Leu His Gln Val Ala Ala Asp Glu Pro365036553660Ile Ala Ile Val Gly Met Ala Cys Arg Phe Pro Gly Gly Val Cys Ser3665 367036753680Pro Glu Glu Leu Trp Glu Leu Val Ala Ser Gly Gly Asp Ala Ile Gly368536903695Glu Phe Pro Ala Gly Arg Gly Trp Asp Leu Glu Gly Leu Phe Asp Ser370037053710Asp Pro Asp Arg Ser Gly Thr Ser Tyr Ala Arg Tyr Gly Gly Phe Leu371537203725Tyr Glu Ala Gly Glu Phe Asp Ala Asp Phe Phe Gly Ile Ser Pro Arg373037353740Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Thr Ser3745 375037553760Trp Glu Ala Phe Glu Arg Ala Gly Ile Asp Pro Leu Ser Met Arg Gly376537703775Ser Arg Thr Gly Val Phe Ala Gly Val Met Tyr His Asp Tyr Ala Ala378037853790Arg Leu His His Val Pro Glu Gly Phe Glu Gly Leu Ile Ala Asn Gly379538003805Ser Ala Gly Ser Val Ala Thr Gly Arg Val Ala Tyr Ser Phe Gly Leu381038153820Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val3825 383038353840Ala Leu His Trp Ala Ala Gln Ala Leu Arg Ala Gly Glu Cys Ser Met384538503855Ala Leu Ala Gly Gly Val Thr Val Met Ser Ser Pro Gly Thr Phe Val
386038653870Glu Phe Ser Arg Gln Arg Gly Leu Ala Ala Asp Gly Arg Cys Lys Ala387538803885Tyr Ser Ala Ala Ala Asp Gly Thr Gly Trp Ala Glu Gly Val Gly Met389038953900Leu Leu Val Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly His Arg Val3905 391039153920Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn392539303935Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Arg Gln394039453950Ala Leu Ala Asn Ala Gly Leu Thr Pro Ala Asp Val Asp Ala Val Glu395539603965Gly His Gly Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala397039753980Leu Leu Ala Ala Tyr Gly Gln His Arg Pro His His Arg Pro Leu Trp3985 399039954000Leu Gly Ser Leu Lys Ser Asn Ile Gly His Ala Gln Ala Ala Ala Gly400540104015Val Gly Gly Val Ile Lys Met Val Met Ala Leu Arg Asn Gly Leu Leu402040254030Pro Gln Thr Leu His Val Asp Glu Pro Thr Pro Gln Val Asp Trp Ser403540404045Thr Gly Ala Val Gln Leu Leu Thr Gln Pro Val Pro Trp Pro Ala Asp405040554060Pro Ala Gly Arg Pro Arg His Ala Gly Val Ser Ser Phe Gly Val Ser4065 407040754080Gly Thr Asn Ala His Val Ile Leu Glu Glu Ala Pro Ala Ala Ala Gly408540904095Gly Ala Ala Gly Gly Gly Val Ser Val Gly Ala Pro Asn Pro Ala Leu410041054110Pro Val Ala Glu Ser Glu Pro Val Pro Val Pro Val Pro Val Ser Ala411541204125Arg Ser Glu Ala Gly Leu Arg Ala Gln Ala Gln Ala Leu Arg Gln Tyr413041354140Val Ala Ala Arg Pro Asp Met Ser Pro Ala Asp Ile Gly Ala Gly Leu4145 415041554160Ala Arg Gly Arg Ala Val Leu Glu His Arg Ala Val Ile Leu Ala Ala416541704175Asp Arg Glu Glu Leu Ala Gln Ala Leu Thr Ala Leu Ala Ala Gly Glu418041854190Pro His Pro His Ile Thr Thr Gly His Thr Arg Gly Ser Asp Arg Gly419542004205Gly Val Val Phe Val Phe Pro Gly Gln Gly Gly Gln Trp Ala Gly Met421042154220Gly Leu Thr Leu Leu Thr Ser Ser Pro Val Phe A1a Glu His Ile Asp4225 423042354240Ala Cys Glu Lys Ala Leu Thr Pro Trp Val Pro Trp Ser Leu Thr Asp424542504255Ile Leu His Arg Asp Pro Asp Asp Pro Ala Trp Gln Gln Ala Asp Val426042654270Val Gln Pro Val Leu Phe Ser Ile Met Val Ser Leu Ala Ala Leu Trp427542804285Arg Ser Tyr Gly Ile Glu Pro Asp Ala Val Leu Gly His Ser Gln Gly429042954300Glu Ile Ala Ala Ala His Ile Cys Gly Ala Leu Ser Leu Lys Asp Ala4305 431043154320Ala Lys Thr Val Ala Leu Arg Ser Gln Ala Leu Ala Ala Val Arg Gly432543304335Arg Gly Ala Met Val Ser Leu Pro Leu Pro Ala Gln Asp Val Gln Gln434043454350Leu Ile Ser Glu Arg Trp Glu Gly Gln Leu Trp Val Ala Ala Leu Asn435543604365Gly Pro His Ser Thr Thr Val Ser Gly Asp Thr Thr Ala Val Glu Glu437043754380Leu Leu Thr His Cys Ala Asp Thr Gly Leu Arg Ala Lys Arg Ile Pro4385 439043954400Val Asp Tyr Ala Ser His Cys Pro His Val Gln Pro Leu His Asp Glu440544104415Leu Leu His Leu Leu Gly Asp Ile Thr Pro Gln Pro Ser Thr Met Pro442044254430Phe Phe Ser Thr Val Val Gly His Leu Val Trp Tyr Thr Thr Thr Leu443544404445Asp Ala Ala Tyr Trp Tyr Arg Asn Leu His Gln Pro Val Arg Phe Ser445044554460His Ala Ile Gln Thr Leu Thr Asp Asp Gly His Arg Pro Phe Ile Glu4465 447044754480Ile Ser Pro His Pro Thr Leu Val Pro Ala Ile Glu Asp Thr Thr Glu448544904495Asn Thr Thr Glu Asn Ile Thr Ala Thr Gly Ser Leu Arg Arg Gly Asp450045054510Asn Asp Thr His Arg Phe Leu Thr Ala Leu Ala His Thr His Thr Thr451545204525Gly Ile Arg Thr Pro Thr Thr Trp His His His Tyr Thr Gln Thr His453045354540Pro His Pro His Asn His His Leu Asp Leu Pro Thr Tyr Pro Phe Gln4545 455045554560His Gln His Tyr Trp Leu Gln Pro Pro Thr Thr Thr Thr Asp Leu Thr
456545704575Thr Thr Gly Leu Thr Pro Thr His His Pro Leu Leu Thr Ala Thr Leu458045854590Thr Leu Ala Asn Asn Asn Thr Gln Leu Leu Thr Gly Arg Leu Ser Leu459546004605Arg Thr His Pro Trp Leu Thr Asp His Thr Val Val Gly Thr Thr Leu461046154620Val Pro Gly Thr Ala Leu Leu Glu Leu Ala Leu Gln Ala Thr Thr Thr4625 463046354640Asp His Leu Glu Glu Leu Ala Leu His Thr Pro Leu Val Ile Pro Arg464546504655Glu Gly Ala Val Asp Val Gln Val His Ile Asn Pro Pro Asp Asp Thr466046654670Asp Thr Arg Ser Leu Thr Ile Tyr Ser Arg Ser Glu Asn Ala Pro Ala467546804685Ala Ala Pro Trp Arg His His Ala Thr Ala Val Leu Gly Thr Lys Thr469046954700Ser Arg Ile Glu Thr Gly Arg Ser His Asp Asp Leu Ser Met Trp Pro4705 471047154720Pro Ala Gly Ala Val Arg Cys Ala Asp Glu Glu Leu Ala Ala Leu Tyr472547304735Gly Asp Tyr Glu Ala Asn Gly Phe Val Tyr Gly Pro Ala Phe Arg Gly474047454750Leu Thr Ala Ala Trp Arg Leu Gly Asp Glu Val Phe Ala Glu Val Arg475547604765Leu Pro Glu Gln Val His Gly Glu Ala Ser Ala Tyr Asn Leu His Pro477047754780Ala Leu Leu Asp Ala Ala Leu His Ala Ala Ala Phe Ala Pro Ser Gly4785 479047954800Ser Leu Pro Gln Gly Ser Val Pro Phe Ser Phe Thr Gly Val Thr Leu480548104815His Ala Ala Asn Ala Ser Ser Leu Arg Val Arg Leu Ser Pro Ala Asp4820 48254830Pro Asn Ser Gly His Ala Ala Val Ser Val Leu Val Thr Asp Asp Thr483548404845Gly Thr Pro Val Ala Ser Val Glu Ala Leu Ala Val Arg Pro Leu Ala485048554860Ala Asp Glu Leu Arg Ala Ala Glu Arg Ala Val Gln Arg Ala Glu Leu4865 487048754880Phe Asp Met Lys Trp Val Glu Val Pro Ser Asp Val Leu Val Ser Gly488548904895Gly Ala Ser Val Val Val Leu Asp Gly Ala Asp Asp Leu Val Gly Leu490049054910Ala Ala Glu Glu Asp Gly Val Pro Gly Val Val Val Leu Arg Cys Pro491549204925Asp Ala Gly Ala Asp Gly Gly Gly Gly Gly Gly Gly Val Gly Glu Val493049354940Val Gly Gly Val Leu Gly Val Val Gln Gly Trp Leu Gly Leu Glu Arg4945 495049554960Phe Ala Gly Ser Arg Leu Val Val Val Thr Arg Gly Ala Val Val Ala496549704975Gly Pro Glu Asp Gly Pro Val Asp Gly Pro Val Asp Val Val Gly Ala4980 49854990Ala Val Trp Gly Leu Val Arg Ser Ala Gln Ala Glu His Pro Asp Arg499550005005Phe Val Leu Leu Asp Leu Asp Thr Asp Leu Asp Ser Gly Ala Asp Arg501050155020Asp Ala Gly Asn Glu Ala Gly Met Gly Ser Gly Leu Asp Gly Gly Arg5025 503050355040Val Ala Ala Val Val Ala Cys Gly Glu Pro Gln Leu Ala Val Arg Gly504550505055Glu Arg Val Leu Ala Ala Arg Leu Thr Arg Leu Glu Ser Pro Val Asp506050655070Val Ser Gly Arg Glu Val Leu Pro Trp Leu Ser Gly Gly Ser Val Leu507550805085Val Thr Gly Gly Thr Gly Val Leu Gly Ala Ala Val Ala Arg His Leu509050955100Ala Gly Val Cys Gly Val Arg Asp Leu Leu Leu Val Ser Arg Arg Gly5105 511051155120Pro Asp Ala Pro Gly Ala Glu Gly Leu Arg Ala Glu Leu Ala Ala Leu512551305135Gly Ala Glu Val Arg Ile Val Ala Cys Asp Val Gly Glu Arg Arg Glu514051455150Val Val Arg Leu Leu Glu Gly Val Pro Ala Gly Cys Pro Leu Thr Gly515551605165Val Val His Ala Ala Gly Val Leu Asp Asp Ala Thr Ile Ala Ser Leu517051755180Thr Pro Glu Arg Leu Gly Thr Val Phe Ala Ala Lys Val Asp Ala Ala5185 519051955200Leu Leu Leu Asp Glu Leu Thr Arg Gly Met Glu Leu Ser Ala Phe Val520552105215Leu Phe Ser Ser Ala Ala Gly Ile Leu Gly Ser Ala Gly Gln Gly Asn522052255230Tyr Ala Ala Ala Asn Ala Ala Leu Asp Ala Leu Ala Tyr Arg Arg Arg523552405245Ala Ala Gly Leu Pro Gly Val Ser Leu Ala Trp Gly Leu Trp Glu Glu525052555260Ala Ser Gly Met Thr Gly His Leu Ala Gly Thr Asp His Arg Arg Ile5265 527052755280Ile Arg Ser Gly Leu His Pro Met Ser Thr Pro Asp Ala Leu Ala Leu528552905295Phe Asp Ala Ala Leu Ala Leu Asp Arg Pro Val Leu Leu Pro Ala Asp530053055310Leu Arg Pro Ala Pro Pro Leu Pro Pro Leu Leu Gln Asp Leu Leu Pro531553205325Ala Thr Arg Arg Arg Thr Thr Arg Thr Thr Thr Thr Gly Gly Ala Asp533053355340Asn Gly Ala Gln Leu His Gly Arg Leu Ala Gly Gln Thr His Glu Gln5345 535053555360Gln His Thr Thr Leu Leu Ala Leu Val Arg Ser His Ile Ala Thr Val536553705375Leu Gly His Thr Thr Pro Asp Thr Ile Pro Pro Asp Arg Ala Phe Arg538053855390Asp Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu Arg Asn Arg Leu539554005405Ser His Thr Thr Gly Leu Arg Leu Pro Thr Thr Leu Ala Phe Asp His541054155420Pro Asn Pro Thr Thr Leu Thr His His Leu His Thr Gln Leu Val Ser5425 543054355440Lys Gly Leu Thr Ala Ala Ala Glu Pro Asp Ala Ala Thr Thr Pro Pro544554505455Gly Leu Pro Ser Leu Leu Ser Glu Leu Glu Arg Leu Glu Ala Val Val546054655470Leu Ser Ser Thr Thr Ser Ser Ala Ala Pro Leu Asp Asp Gly Ala Arg547554805485Thr Arg Leu Ala Ser Arg Leu His Ser Leu Ala Gln Lys Leu Asn Gly549054955500Asp Asp Thr Ala Pro Asp Leu Ala Glu Thr Ser Asp Glu Glu Met Phe5505 551055155520Ala Leu Ile Asp Arg Glu Val Gly Phe Glu Ser Gln55255530<210>7<211>483<212>DNA<213>除蟲鏈霉菌<220><221>CDS<222>(1)..(486)<400>7tac tgg ctc gaa agc aca cag ccc ggt gcc ggc aac gtg tca gca gcc 48Tyr Trp Leu Glu Ser Thr Gln Pro Gly Ala Gly Asn Val Ser Ala Ala1 5 10 15gga ctc gac ccc acc gaa cac ccc cta ctc ggc gcc aca ttg gaa ctg 96Gly Leu Asp Pro Thr Glu His Pro Leu Leu Gly Ala Thr Leu Glu Leu20 25 30gcg act gac ggt gga gcg ctt ctt gca ggg cgc ttg tct ttg agg tcg 144Ala Thr Asp Gly Gly Ala Leu Leu Ala Gly Arg Leu Ser Leu Arg Ser35 40 45cat ccg tgg ctg gct gac tac gag gtc ggc ggc acg gtg ctg ctg tcg 192His Pro Trp Leu Ala Asp Tyr Glu Val Gly Gly Thr Val Leu Leu Ser50 55 60ggc gcc acc tic ctc gaa ctc gcc ctt cat gcg ggc aca tac gtg ggc 240Gly Ala Thr Phe Leu Glu Leu Ala Leu His Ala Gly Thr Tyr Val Gly65 70 75 80tgc gac cga gtg gat gag ctg acg ctg cat gcg ccg ctg gtg gtt cct 288Cys Asp Arg Val Asp Glu Leu Thr Leu His Ala Pro Leu Val Val Pro85 90 95gtg gat ggg ggt gtg agt gtg cag gtt ggg gtt gcg gct gcg gat ggg 336Val Asp Gly Gly Val Ser Val Gln Val Gly Val Ala Ala Ala Asp Gly100 105 110gag ggg cgg cgt ttg gtg agt gtg tat gcg cgg ggt ggg agt gct tgt 384Glu Gly Arg Arg Leu Val Ser Val Tyr Ala Arg Gly Gly Ser Ala Cys115 120 125ggt ggg ggt ggt gcg tcg ggt ggg gtg tgg acg tgt cat gcc tcg ggg 432Gly Gly Gly Gly Ala Ser Gly Gly Val Trp Thr Cys His Ala Ser Gly130 135 140gtg ctg 438Val Leu145<210>8<211>146<212>PRT<213>除蟲鏈霉菌<400>8Tyr Trp Leu Glu Ser Thr Gln Pro Gly Ala Gly Asn Val Ser Ala Ala1 5 10 15Gly Leu Asp Pro Thr Glu His Pro Leu Leu Gly Ala Thr Leu Glu Leu20 25 30Ala Thr Asp Gly Gly Ala Leu Leu Ala Gly Arg Leu Ser Leu Arg Ser35 40 45His Pro Trp Leu Ala Asp Tyr Glu Val Gly Gly Thr Val Leu Leu Ser50 55 60Gly Ala Thr Phe Leu Glu Leu Ala Leu His Ala Gly Thr Tyr Val Gly65 70 75 80Cys Asp Arg Val Asp Glu Leu Thr Leu His Ala Pro Leu Val Val Pro85 90 95Val Asp Gly Gly Val Ser Val Gln Val Gly Val Ala Ala Ala Asp Gly100 105 110Glu Gly Arg Arg Leu Val Ser Val Tyr Ala Arg Gly Gly Ser Ala Cys115 120 125Gly Gly Gly Gly Ala Ser Gly Gly Val Trp Thr Cys His Ala Ser Gly130 135 140Val Leu145<210>9<211>30<212>DNA<213>人工序列<220><223>基于SEQ ID NO1的9098到9127之間的序列的引物<400>9ggctggctga ctacgaggtc ggcggcacgg 30<210>10<211>30<212>DNA<213>人工序列<220><223>基于SEQ ID NO1的9193到9222之間的序列的引物<400>10cggcgcatgc agcgtcagct catccactcg 30<210>11<211>30<212>DNA<213>人工序列<220><223>基于SEQ ID NO1的9098到9127之間的序列的反義引物<400>11ccgtgccgcc gacctcgtag tcagccagcc 30<210>12<211>30<212>DNA<213>人工序列<220><223>基于SEQ ID NO1的8948到8977之間的序列的引物<400>12actggctcga aagcacacag cccggtgccg 30<210>13<211>10<212>PRT<213>除蟲鏈霉菌<220><223>Xaa代表任何氨基酸<400>13His Xaa Xaa Xaa Gly Xaa Xaa Xaa Xaa Pro1510<210>14<211>10<212>PRT<213>除蟲鏈霉菌<220><223>Xaa代表任何氨基酸<400>14His Xaa Xaa Xaa Gly Xaa Xaa Xaa Xaa Ser1510<210>15<211>10<212>PRT<213>除蟲鏈霉菌<220><223>Xaa代表任何氨基酸<400>15Tyr Xaa Xaa Xaa Gly Xaa Xaa Xaa Xaa Ser1510<210>16<211>10<212>PRT<213>除蟲鏈霉菌<400>16His Ala Val Gly Gly Thr Val Leu Leu Ser1510
權(quán)利要求
1.一種編碼除蟲菌素糖苷配基合成酶的DNA。
2.一種含有選自下列一組的核苷酸序列的DNASEQ ID NO1的1-11916和11971-30688號(hào)核苷酸，和SEQ ID NO2的1-14643和14824-31419號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼一種具有除蟲菌素糖苷配基合成酶活性的多肽的DNA。
3.如權(quán)利要求1或2的DNA，其中，該DNA包括編碼除蟲菌素糖苷配基合成酶功能域的DNA。
4.如權(quán)利要求3的DNA，其中，該DNA編碼選自下列一組的除蟲菌素糖苷配基合成酶功能域一種編碼具有酰基轉(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA；一種編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、β-酮脂酰-ACP還原酶活性和?；d體蛋白活性的多肽的DNA；一種編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性和?；d體蛋白活性的多肽的DNA；一種編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、和?；d體蛋白活性的多肽的DNA；和一種編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、?；d體蛋白活性和硫酯酶活性的多肽的DNA。
5.如權(quán)利要求4的DNA，其中，所述編碼具有?；D(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA是包括SEQ ID NO1的85-1353號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有酰基轉(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA。
6.如權(quán)利要求4的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性、酰基轉(zhuǎn)移酶活性、β-酮脂酰-ACP還原酶活性、和酰基載體蛋白活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1441-6180、15217-19938和20008-24690號(hào)核苷酸和SEQ ID NO2的100-4692和14935-20334號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、β-酮脂酰-ACP還原酶活性、和?；d體蛋白活性的多肽的DNA。
7.如權(quán)利要求4的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、和?；d體蛋白活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的6256-11658和24781-30309號(hào)核苷酸，和SEQ ID NO2的20413-25734和25810-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、和?；d體蛋白活性的多肽的DNA。
8.如權(quán)利要求4的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性、酰基轉(zhuǎn)移酶活性、和?；d體蛋白活性的多肽的DNA是一種包括SEQ ID NO1的12076-15147號(hào)核苷酸或SEQ ID NO2的4771-7818號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA。
9.如權(quán)利要求4的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、酰基載體蛋白活性、和硫酯酶活性的多肽的DNA是一種包括SEQ ID NO2的7906-14619號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、?；d體蛋白活性、和硫酯酶活性的多肽的DNA。
10.如權(quán)利要求4的DNA，其中，所述編碼具有?；D(zhuǎn)移酶活性的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的85-1032、7906-8829、13756-14694、16917-17862、21658-22584和26413-27336號(hào)核苷酸，和SEQ ID NO2的1648-2673、6322-7344、9676-10773、16543-17565、21991-23019和27367-28392號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；D(zhuǎn)移酶活性的多肽的DNA。
11.如權(quán)利要求4的DNA，其中，所述編碼具有?；d體蛋白活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1096-1353、5935-6180、11413-11658、14902-15147、19693-19938、24445-24690和30064-30309號(hào)核苷酸，和SEQ ID NO2的4447-4692、7573-7818、13378-13659、20089-20334、25489-25734和30880-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；d體蛋白活性的多肽的DNA。
12.如權(quán)利要求4的DNA，其中，所述編碼具有β-酮脂酰-ACP合成酶活性的多肽的DNA是一種包括選自下列一組的核苷酸序列SEQ ID NO1的1441-2742、6256-7545、12076-13368、15217-16506、20008-21297和24781-26079號(hào)核苷酸，和SEQ ID NO1的100-1383、4771-6060、7906-9258、14935-16224、20413-21705和25810-27102號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性的多肽的DNA。
13.如權(quán)利要求4的DNA，其中，所述編碼具有β-酮脂酰-ACP還原酶活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的5143-5676、10609-11142、18886-19419、23602-24138和29227-29760號(hào)核苷酸和SEQ ID NO2的3634-4188、12547-13104、19285-19842、24685-25242和30076-30633號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP還原酶活性的多肽的DNA。
14.如權(quán)利要求4的DNA，其中，所述編碼具有脫水酶活性的多肽的DNA是一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的8947-9384和27475-27894號(hào)核苷酸，和SEQ ID NO2的10885-11289、23149-23529和28516-28878號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有脫水酶活性的多肽的DNA。
15.如權(quán)利要求4的DNA，其中，所述編碼具有硫酯酶活性的多肽的DNA是一種包括SEQ ID NO2的13879-14619號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有硫酯酶活性的多肽的DNA。
16.如權(quán)利要求3或4的DNA，其中，所述編碼除蟲菌素糖苷配基合成酶功能域的DNA是一種編碼具有增強(qiáng)了的或減弱了的所述功能域的活性的多肽的突變型DNA。
17.如權(quán)利要求16的DNA，其中，所述編碼具有減弱了的除蟲菌素糖苷配基合成酶功能域的活性的多肽的DNA，是包括SEQ ID NO7的核苷酸序列的DNA。
18.一種編碼除蟲菌素糖苷配基合成酶功能域的DNA，它包括選自下列一組的核苷酸序列SEQ ID NO1的85-1032、1096-1353、1441-2742、3148-4068、5143-5676、5935-6180、6256-7545、7906-8829、8947-9384、10609-11142、11413-11658、12076-13368、13756-14694、14902-15147、15217-16506、16917-17862、18886-19419、19693-19938、20008-21297、21658-22584、23602-24138、24445-24690、24781-26079、26413-27335、27475-27894、29227-29760和30064-30309號(hào)核苷酸，和SEQ ID NO2的100-1383、1648-2673、3634-4188、4447-4692、4771-6060、6322-7344、7573-7818、7906-9258、9676-10773、10885-11289、12547-13104、13378-13659、13879-14619、14935-16224、16543-17565、17689-18066、19285-19842、20089-20334、20413-21705、21991-23019、23149-23529、24685-25242、25489-25734、25810-27102、27367-28392、28516-28878、30076-30633、和30880-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有除蟲菊素糖苷配基合成酶功能域活性的多肽的DNA。
19.一種包括SEQ ID NO1的85-1353號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；D(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA。
20.一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1441-6180、15217-19938和20008-24690號(hào)核苷酸，和SEQ ID NO2的100-4692號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、β-酮脂酰-ACP還原酶活性和?；d體蛋白活性的多肽的DNA。
21.一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的6256-11658和24781-30309號(hào)核苷酸，和SEQ ID NO2的14935-20334、20413-25734、和25810-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性和?；d體蛋白活性的多肽的DNA。
22.一種包括SEQ ID NO1的12076-15147號(hào)核苷酸或SEQ IDNO2的4771-7818號(hào)核苷酸的核苷酸序列的DNA；一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性和?；d體蛋白活性的多肽的DNA。
23.一種包括SEQ ID NO2的7906-14619號(hào)核苷酸的核苷酸序列的DNA；一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性、?；D(zhuǎn)移酶活性、脫水酶活性、β-酮脂酰-ACP還原酶活性、酰基載體蛋白活性和硫酯酶活性的多肽的DNA。
24.一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的85-1032、7906-8829、13756-14694、16917-17862、21658-22584和26413-27336號(hào)核苷酸，和SEQ ID NO2的1648-2673、6322-7344、9676-10773、16543-17565、21991-23019和27367-28392號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；D(zhuǎn)移酶活性的多肽的DNA。
25.一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1096-1353、5935-6180、11413-11658、14902-15147、19693-19938、24445-24690和30064-30309號(hào)核苷酸，和SEQ ID NO2的4447-4692、7573-7818、13378-13659、20089-20334、25489-25734和30880-31125號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有?；d體蛋白活性的多肽的DNA。
26.一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的1441-2742、6256-7545、12076-13368、15217-16506、20008-21297和24781-26079號(hào)核苷酸，和SEQ ID NO1的100-1383、4771-6060、7906-9258、14935-16224、20413-21705和25810-27102號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP合成酶活性的多肽的DNA。
27.一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的5143-5676、10609-11142、18886-19419、23602-24138和29227-29760號(hào)核苷酸，和SEQ ID NO2的3634-4188、12547-13104、19285-19842、24685-25242、和30076-30633號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有β-酮脂酰-ACP還原酶活性的多肽的DNA。
28.一種包括選自下列一組的核苷酸序列的DNASEQ ID NO1的8947-9384和27475-27894號(hào)核苷酸，和SEQ ID NO2的10885-10289、17689-18066、23149-23529和28516-28878號(hào)核苷酸；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有脫水酶活性的多肽的DNA。
29.一種包括SEQ ID NO2的13879-14619號(hào)核苷酸的核苷酸序列的DNA；或一種能在嚴(yán)格條件下與該DNA雜交，并且編碼具有硫酯酶活性的多肽的DNA。
30.一種包括SEQ ID NO7所示核苷酸序列的DNA。
31.一種由上述(1)-(29)中任一項(xiàng)所述的DNA編碼的多肽。
32.一種包括SEQ ID NO3-6中任一項(xiàng)的氨基酸序列的多肽；或一種包括在上述SEQ ID NO3-6中任一項(xiàng)的氨基酸序列中缺失、取代或添加了一個(gè)或多個(gè)氨基酸的氨基酸序列，并且具有除蟲菊素糖苷配基合成酶活性的多肽。
33.一種包括選自下列一組的氨基酸序列的多肽SEQ ID NO3的29-344、366-451、481-914、1050-1356、1715-1892、1979-2060、2086-2515、2983-3128、3537-3714和3805-3886號(hào)氨基酸，SEQ ID NO4的36-466、596-908、978-1059、1083-1512、1653-1964、2306-2483、2575-2656、2680-3109、32030-3538、3878-4056、4159-4240、4271-4703、4815-5122、5753-5930和6032-6113號(hào)氨基酸，SEQ ID NO5的34-461、550-891、1212-1396、1483-1564、1591-2020、2108-2448、2525-2606、2636-3086、3226-3591、3629-3763、4183-4363、4460-4553和4627-4873號(hào)氨基酸，SEQ ID NO6的38-467、574-914、956-1081、1488-1673、1756-1837、1864-2294、2390-3732、2776-2902、3288-3473、3556-3637、3663-4093、4182-4523、4565-4685、5085-5270和5353-5434號(hào)氨基酸；或一種包括在上述選擇氨基酸序列中缺失、取代或添加了一個(gè)或多個(gè)氨基酸的氨基酸序列，并且具有除蟲菊素糖苷配基合成酶功能域活性的多肽。
34.一種包括權(quán)利要求1-30中任一項(xiàng)的DNA的重組載體。
35.一種通過將權(quán)利要求1-30中任一項(xiàng)的DNA或權(quán)利要求34中的重組載體導(dǎo)入宿主細(xì)胞而獲得的轉(zhuǎn)化體。
36.如權(quán)利要求35的轉(zhuǎn)化體，其中，所述宿主細(xì)胞是產(chǎn)除蟲菊素細(xì)菌菌株。
37.如權(quán)利要求35或36的轉(zhuǎn)化體，其中，所述宿主細(xì)胞是除蟲鏈霉菌K2038(FERM BP2775)。
38.一種生產(chǎn)除蟲菊素糖苷配基合成酶或除蟲菊素糖苷配基合成酶功能域多肽的方法，包括在一種培養(yǎng)基中培養(yǎng)權(quán)利要求35-37中任一項(xiàng)的轉(zhuǎn)化體，以便在該培養(yǎng)基中形成并積累所述酶或功能域多肽，和從所述培養(yǎng)基回收所述酶或功能域多肽。
39.一種生產(chǎn)除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基的方法，包括在一種培養(yǎng)基中培養(yǎng)權(quán)利要求35-37中任一項(xiàng)的轉(zhuǎn)化體，以便在該培養(yǎng)基中形成并積累所述除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基，和從所述培養(yǎng)基回收所述除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基。
40.一種生產(chǎn)除蟲菊素或改變了的除蟲菊素的方法，包括在一種培養(yǎng)基中培養(yǎng)權(quán)利要求35-37中任一項(xiàng)的轉(zhuǎn)化體，以便在該培養(yǎng)基中形成并積累所述除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基，將所述除蟲菊素糖苷配基或改變了的除蟲菊素糖苷配基糖基化，和回收除蟲菊素或改變了的除蟲菊素。
41.如權(quán)利要求40的方法，其中，改變了的除蟲菊素是一種從除蟲菊素B1a變成除蟲菊素B2a的除蟲菊素。
42.一種可以通過權(quán)利要求40的方法所獲得的改變了的除蟲菊素。
43.一種具有相當(dāng)于權(quán)利要求1或2中的DNA的核苷酸序列上的5-60個(gè)連續(xù)核苷酸的序列的寡核苷酸；或一種與所述寡核苷酸具有序列互補(bǔ)性的寡核苷酸。
全文摘要
本發(fā)明提供了一種分離的DNA,它含有編碼除蟲菌素糖苷配基合成酶功能域的DNA序列,它是一種參與聚酮化合物生物合成的多功能酶蛋白,或其具有除蟲菌素糖苷配基合成酶活性的變體,具體地講,源于除蟲鏈霉菌DNA的一種序列上的功能性組件和亞組件,由所述DNA或其變體所編碼的多肽或其變體,一種含有所述DNA或其變體的載體,一種用所述DNA、其改進(jìn)形式或所述載體轉(zhuǎn)化過的宿主細(xì)胞,和一種生產(chǎn)除蟲菌素的方法。
文檔編號(hào)C12N15/52GK1349560SQ00806725
公開日2002年5月15日 申請(qǐng)日期2000年2月23日 優(yōu)先權(quán)日1999年2月24日
發(fā)明者大村智, 池田治生 申請(qǐng)人:社團(tuán)法人北里研究所