CN111684066A

CN111684066A - 环状肽化合物合成相关基因、使用该基因的环状肽化合物制造方法以及具有该基因的转化体

Info

Publication number: CN111684066A
Application number: CN201780088071.3A
Authority: CN
Inventors: 久保崇; 町田雅之; 梅村舞子; 阿部敬悦; 吉见启; 藤冈智则; 山口滋生; 河合清
Original assignee: Tohoku University NUC; Kumiai Chemical Industry Co Ltd; National Institute of Advanced Industrial Science and Technology AIST
Current assignee: Tohoku University NUC; Kumiai Chemical Industry Co Ltd
Priority date: 2017-01-05
Filing date: 2017-12-27
Publication date: 2020-09-18
Anticipated expiration: 2037-12-27
Also published as: EP3567107C0; JP7072750B2; US11230726B2; CA3048176A1; CN111684066B; TW201829771A; PH12019501577A1; JPWO2018128140A1; US20190316164A1; ES3034015T3; BR112019013234A2; EP3567107A4; AR110725A1; EP3567107A1; EP3567107B1; KR102633026B1; TWI826363B; KR20190117511A; US11946086B2; WO2018128140A1

Abstract

本发明提供鉴定一种参与由弯孢属(Curvularia)丝状真菌产生的环状肽化合物生物合成的基因簇，并建立该环状肽化合物的合成系统。该基因簇编码如下蛋白质：所述蛋白质具有第一模块～第十模块，且具有形成由弯孢属(Curvularia)丝状真菌产生的环状肽化合物基本肽骨架的非核糖体肽合成活性。

Description

环状肽化合物合成相关基因、使用该基因的环状肽化合物制造方法以及具有该基因的转化体

技术领域

本发明涉及一种参与由弯孢属(Curvularia)丝状真菌产生的环状肽化合物合成的新型环状肽化合物合成相关基因，还涉及使用该环状肽化合物合成相关基因的环状肽化合物的制造方法，以及具有该环状肽化合物合成相关基因的转化体，其中，所述环状肽化合物对菌类具有杀菌作用。

背景技术

已知由弯孢属(Curvularia)丝状真菌产生的作为CAS143380-71-6而被公知的特定环状肽化合物(以下称为KK-1)对植物病原菌尤其是真菌类表现出强力的杀菌作用(专利文献1)。但是，尽管KK-1表现出强力杀菌作用，却尚未作为农药实现商业化。主要原因可以举出：KK-1化学结构复杂，因此难以进行化学合成；即使可以化学合成KK-1，但由于KK-1化学结构复杂，导致成本高昂。此外，即使尝试通过培养弯孢属(Curvularia)丝状真菌来制造KK-1，也不能保证足够的生产量。

至今一直都是从包括真菌、放线菌和细菌在内的微生物产生的次级代谢产物来开发药物和农药。经过对以与弯孢属(Curvularia)相同丝状真菌的曲霉属(Aspergillus)为代表的一些真菌进行基因组分析，结果表明：存在一种生物合成基因簇，其参与包括聚酮化合物、非核糖体肽、萜类或生物碱等在内的多种次级代谢产物的生物合成(非专利文献1)。但是有报告称，根据近年的丝状真菌基因组分析和分子生物学研究结果可知，在一般的丝状真菌培养方法中，丝状真菌的次级代谢产物生物合成基因的转录水平低(非专利文献2)。

因此，为了发挥潜在的次级代谢产物的生产能力，正在尝试称为合成生物学方法，其通过生物合成基因簇的活化(非专利文献3)和在芽殖酵母等适当的异种中进行表达，来合成足够量的次级代谢产物。

现有技术文献

专利文献

专利文献1：日本特表平8-504165号公报

非专利文献

非专利文献1：Machida,M.,et al.,Nature,2005.438(7071)：p.1157-1161

非专利文献2：Georgianna,D.R.et al.,：Mol.Plant.Pathol.,11,213(2010)非专利文献3：Brakhage,Fungal Genetics and Biology,2011.48(1)：p.15-22.

发明内容

发明所要解决的问题

关于由弯孢属(Curvularia)丝状真菌产生的KK-1，考虑与上述次级代谢产物同样地也能够通过使用合成生物学方法来产生。但是，弯孢属(Curvularia)丝状真菌的基因组基本未被明确，参与产生KK-1的基因簇也不明。

因此，鉴于上述实际情况，本发明的一个目的在于鉴定一种参与由弯孢属(Curvularia)丝状真菌产生的KK-1的生物合成的基因簇，并提供KK-1的合成系统。

解决问题的技术方案

本发明人为了达到上述目的而进行了潜心研究，结果能够从棒状弯孢菌(Curvularia clavata)基因组中鉴定出多种非核糖体肽合成酶(nonribosomal peptidesynthetase；NRPS)基因，从而成功地从中鉴定出参与KK-1合成的NRPS基因和含有该NRPS基因的基因簇，从而完成了本发明。

本发明包含以下内容：

(1)一种环状肽化合物合成相关基因，其编码如下蛋白质，所述蛋白质从N末端侧起依次具有以下各模块：

第一模块，其从N末端侧起依次具有：由SEQ ID NO:1所示的氨基酸序列或由与SEQID NO:1所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第一腺苷酰化结构域、由SEQ ID NO:2所示的氨基酸序列或由与SEQ ID NO:2所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第一肽基载体蛋白结构域；

第二模块，其从N末端侧起依次具有：由SEQ ID NO:3所示的氨基酸序列或由与SEQID NO:3所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第一缩合结构域、由SEQ ID NO:4所示的氨基酸序列或由与SEQ ID NO:4所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第二腺苷酰化结构域、由SEQ ID NO:5所示的氨基酸序列或由与SEQID NO:5所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第二肽基载体蛋白结构域；

第三模块，其从N末端侧起依次具有：由SEQ ID NO:6所示的氨基酸序列或由与SEQID NO:6所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第二缩合结构域、由SEQ ID NO:7所示的氨基酸序列或由与SEQ ID NO:7所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第三腺苷酰化结构域、由SEQ ID NO:8所示的氨基酸序列或由与SEQID NO:8所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第一N-甲基转移酶结构域、由SEQ ID NO:9所示的氨基酸序列或由与SEQ ID NO:9所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第三肽基载体蛋白结构域；

第四模块，其从N末端侧起依次具有：由SEQ ID NO:10所示的氨基酸序列或由与SEQ ID NO:10所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第三缩合结构域、由SEQ ID NO:11所示的氨基酸序列或由与SEQ ID NO:11所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第四腺苷酰化结构域、由SEQ ID NO:12所示的氨基酸序列或由与SEQ ID NO:12所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第四肽基载体蛋白结构域；

第五模块，其从N末端侧起依次具有：由SEQ ID NO:13所示的氨基酸序列或由与SEQ ID NO:13所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第四缩合结构域、由SEQ ID NO:14所示的氨基酸序列或由与SEQ ID NO:14所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第五腺苷酰化结构域、由SEQ ID NO:15所示的氨基酸序列或由与SEQ ID NO:15所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第二N-甲基转移酶结构域、由SEQ ID NO:16所示的氨基酸序列或由与SEQ ID NO:16所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第五肽基载体蛋白结构域；

第六模块，其从N末端侧起依次具有：由SEQ ID NO:17所示的氨基酸序列或由与SEQ ID NO:17所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第五缩合结构域、由SEQ ID NO:18所示的氨基酸序列或由与SEQ ID NO:18所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第六腺苷酰化结构域、由SEQ ID NO:19所示的氨基酸序列或由与SEQ ID NO:19所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第三N-甲基转移酶结构域、由SEQ ID NO:20所示的氨基酸序列或由与SEQ ID NO:20所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第六肽基载体蛋白结构域；

第七模块，其从N末端侧起依次具有：由SEQ ID NO:21所示的氨基酸序列或由与SEQ ID NO:21所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第六缩合结构域、由SEQ ID NO:22所示的氨基酸序列或由与SEQ ID NO:22所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第七腺苷酰化结构域、由SEQ ID NO:23所示的氨基酸序列或由与SEQ ID NO:23所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第四N-甲基转移酶结构域、由SEQ ID NO:24所示的氨基酸序列或由与SEQ ID NO:24所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第七肽基载体蛋白结构域；

第八模块，其从N末端侧起依次具有：由SEQ ID NO:25所示的氨基酸序列或由与SEQ ID NO:25所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第七缩合结构域、由SEQ ID NO:26所示的氨基酸序列或由与SEQ ID NO:26所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第八腺苷酰化结构域、由SEQ ID NO:27所示的氨基酸序列或由与SEQ ID NO:27所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第八肽基载体蛋白结构域；

第九模块，其从N末端侧起依次具有：由SEQ ID NO:28所示的氨基酸序列或由与SEQ ID NO:28所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第八缩合结构域、由SEQ ID NO:29所示的氨基酸序列或由与SEQ ID NO:29所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第九腺苷酰化结构域、由SEQ ID NO:30所示的氨基酸序列或由与SEQ ID NO:30所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第五N-甲基转移酶结构域、由SEQ ID NO:31所示的氨基酸序列或由与SEQ ID NO:31所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第九肽基载体蛋白结构域；

第十模块，其从N末端侧起依次具有：由SEQ ID NO:32所示的氨基酸序列或由与SEQ ID NO:32所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第九缩合结构域、由SEQ ID NO:33所示的氨基酸序列或由与SEQ ID NO:33所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第十腺苷酰化结构域、由SEQ ID NO:34所示的氨基酸序列或由与SEQ ID NO:34所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第十肽基载体蛋白结构域、由SEQ ID NO:35所示的氨基酸序列或由与SEQ ID NO:35所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第十缩合结构域，

且所述蛋白质具有由弯孢属(Curvularia)丝状真菌产生的环状肽化合物的非核糖体肽合成活性。

(2)根据(1)所述的环状肽化合物合成相关基因，其特征在于，所述蛋白质为以下(a)～(c)中任一项的蛋白质：

(a)由SEQ ID NO:37所示的氨基酸序列组成的蛋白质；

(b)由与SEQ ID NO:37所示的氨基酸序列具有70％以上同一性的氨基酸序列组成，且具有由弯孢属(Curvularia)丝状真菌产生的环状肽化合物的非核糖体肽合成活性的蛋白质；

(c)由与SEQ ID NO:36所示的碱基序列的互补链在严格条件下杂交的多聚核苷酸所编码，且具有由弯孢属(Curvularia)丝状真菌产生的环状肽化合物的非核糖体肽合成活性的蛋白质。

(3)根据(1)所述的环状肽化合物合成相关基因，其特征在于，所述环状肽化合物合成相关基因来源于弯孢属(Curvularia)丝状真菌。

(4)根据(3)所述的环状肽化合物合成相关基因，其特征在于，所述丝状真菌为棒状弯孢菌(Curvularia clavata)。

(5)一种环状肽化合物合成相关基因，其编码以下(a)～(c)中任一项的蛋白质：

(a)由SEQ ID NO:39所示的氨基酸序列组成的蛋白质；

(b)由与SEQ ID NO:39所示的氨基酸序列具有70％以上同一性的氨基酸序列组成，且具有转录因子活性的蛋白质；

(c)由与SEQ ID NO:38所示的碱基序列的互补链在严格条件下杂交的多聚核苷酸所编码，且具有转录因子活性的蛋白质。

(6)根据(5)所述的环状肽化合物合成相关基因，其特征在于，所述环状肽化合物合成相关基因来源于弯孢属(Curvularia)丝状真菌。

(7)根据(6)所述的环状肽化合物合成相关基因，其特征在于，所述丝状真菌为棒状弯孢菌(Curvularia clavata)。

(8)一种由弯孢属(Curvularia)丝状真菌产生的环状肽化合物的制造方法，所述制造方法包括以下步骤：

培养转化体，所述转化体导入有上述(1)～(4)中任一项所述的环状肽化合物合成相关基因和参与弯孢属(Curvularia)丝状真菌产生环状肽化合物的一组基因；以及

从培养的转化体和/或培养液中回收所述环状肽化合物。

(9)根据(8)所述的环状肽化合物的制造方法，其特征在于，所述一组基因含有以下[1]～[7]的基因：

[1]编码由SEQ ID NO:41所示的氨基酸序列或由与SEQ ID NO:41所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的蛋白质的基因；

[2]编码由SEQ ID NO:43所示的氨基酸序列或由与SEQ ID NO:43所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的蛋白质的基因；

[3]编码由SEQ ID NO:45所示的氨基酸序列或由与SEQ ID NO:45所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的蛋白质的基因；

[4]编码由SEQ ID NO:47所示的氨基酸序列或由与SEQ ID NO:47所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的蛋白质的基因；

[5]编码由SEQ ID NO:49所示的氨基酸序列或由与SEQ ID NO:49所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的蛋白质的基因；

[6]编码由SEQ ID NO:51所示的氨基酸序列或由与SEQ ID NO:51所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的蛋白质的基因；

[7]编码由SEQ ID NO:53所示的氨基酸序列或由与SEQ ID NO:53所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的蛋白质的基因。

(10)根据(8)所述的环状肽化合物的制造方法，其特征在于，所述转化体以米曲霉(Aspergillus oryzae)为宿主。

(11)一种转化体，其导入有上述(1)～(4)中任一项所述的环状肽化合物合成相关基因和参与弯孢属(Curvularia)丝状真菌产生环状肽化合物的一组基因。

(12)根据(11)所述的转化体，其特征在于，所述一组基因含有以下[1]～[7]的基因：

(13)根据(11)所述的转化体，其特征在于，所述转化体以米曲霉(Aspergillusoryzae)为宿主。

(14)一种弯孢属(Curvularia)丝状真菌，其具有上述(1)～(4)中任一项所述的环状肽化合物合成相关基因。

(15)根据(14)所述的弯孢属(Curvularia)丝状真菌，其特征在于，所述弯孢属(Curvularia)丝状真菌为棒状弯孢菌(Curvularia clavata)。

(16)根据(14)所述的弯孢属(Curvularia)丝状真菌，其特征在于，所述弯孢属(Curvularia)丝状真菌的保藏编号为NITE BP-02399。

本说明书包含了作为本申请的优先权基础的日本专利申请号2017-000770号的公开内容。

发明效果

根据本发明，能够提供一种编码参与由弯孢属(Curvularia)丝状真菌产生的环状肽化合物合成的非核糖体肽合成酶的基因，以及其他参与该环状肽化合物合成的一组基因。根据本发明的环状肽化合物合成相关基因，能够构建一种由弯孢属(Curvularia)丝状真菌产生的环状肽化合物的合成系统，从而可以高效地制造该环状肽化合物。

附图说明

图1是说明本发明的环状肽化合物合成相关基因中的模块结构和结构域结构的示意图。

图2是表示由棒状弯孢菌(C.clavata)BAUA-2787株产生的环状肽化合物的结构的图。

图3-1是表示使用InterProScan和antiSMASH程序并通过antiSMASH对实施例中推定的NRPS结构域结构进行分析的结果的图。

图3-2是表示使用InterProScan和antiSMASH程序并通过antiSMASH对实施例中推定的NRPS结构域结构进行分析的结果的图。

图4是表示位于NRPS基因(TRAF01000135000001_J3G)的上游和下游的基因的blastp检索结果的图。

图5是表示推定为KK-1生物合成基因簇的区域的图。

图6是表示根据KK-1产生条件和不产生条件中的基因表达，利用MIDDAS-M进行基因簇检测的结果的特性图。

图7是表示高表达转录因子基因(TF068-005基因)的构建体的示意图。

图8是表示通过“培养1”培养野生株和转录因子高表达株时的KK-1生物合成基因簇构成基因的转录水平的研究结果的特性图。

图9是表示通过“培养2”培养野生株和转录因子高表达株时的KK-1生物合成基因簇构成基因的转录水平的研究结果的特性图。

图10是表示在主培养开始后3天和7天的时刻分成菌体外和菌体内两个方面对野生株和转录因子高表达株的KK-1生产量进行考察的结果的特性图。

图11是表示通过“培养3”培养野生株和转录因子高表达株时的KK-1生产量的研究结果和固体培养的情形的特性图。

图12是表示CcpyrG基因破坏用质粒的构建的示意图。

图13是表示用于破坏转录因子基因(TF068-005基因)的构建体的示意图。

图14是通过PCR扩增的TF068-005基因的上游区域、下游区域和选择标记基因pyrG的电泳照片。

图15是表示用TF068-005基因破坏构建体转化CcpyrG基因破坏株的方法的示意图。

图16是表示对转录因子基因(TF068-005基因)破坏株和野生株实施的抗菌活性试验的结果的特性图。

图17是表示对转录因子基因(TF068-005基因)破坏株实施的全面的基因表达分析(RNA-seq)的结果的特性图。

图18是表示对转录因子基因(TF068-005基因)破坏株实施的KK-1生产量分析的结果的特性图。

图19是表示对KK-1生物合成基因簇中所含有的各基因制作的基因破坏构建体的示意图。

图20是表示利用对KK-1生物合成基因簇中所含有的各基因制作的基因破坏构建体来转化CcpyrG基因破坏株的方法的示意图。

图21是表示对各基因破坏株和转录因子基因破坏株研究KK-1生产率的结果的特性图。

图22是表示在导入KK-1生物合成基因簇时使用的载体的构建方案的示意图。

图23是表示利用Cre-loxP系统分2个阶段将NRPS基因的前半部分和后半部分导入的方案的示意图。

图24是表示在分2个阶段将NRPS基因的前半部分和后半部分导入后，同时导入装载有7个基因的3种载体的方案的示意图。

图25是表示通过定量实时PCR分析导入了KK-1生物合成基因簇的米曲霉中导入的基因的表达量的结果的特性图。

图26是表示导入了KK-1生物合成基因簇的米曲霉中KK-1的LC/MS分析结果和对该米曲霉的抗菌活性试验结果的特性图。

具体实施方式

下面对本发明进行详细说明。

本发明的环状肽化合物合成相关基因，是指参与由弯孢属(Curvularia)丝状真菌产生的环状肽化合物合成的一组基因(基因簇(Gene cluster))中所含有的各个基因。该环状肽化合物如日本特表平8-504165号公报(或WO93/12659)所公开的，由下式表示。

[化1]

(其中，在式中，各氨基酸残基和乳酸残基可以独立地为L型或D型。)

予以说明，环状肽化合物(以下有时也称为KK-1)的化合物名称为酪氨酸,N-[N-[N-[N-[N-[N-[N-[N-[[1-(2-羟基-1-氧代丙基)-2-哌啶基]羰基]-N-甲基缬氨酰基]缬氨酰基]-N-甲基-a-天冬氨酰]-N-甲基缬氨酰基]-N-甲基异亮氨酰基]甘氨酰]-N-甲基缬氨酰基]-O-甲基-,d2-内酯(9CI)。

产生该环状肽化合物的弯孢属(Curvularia)丝状真菌，代表性地可举出棒状弯孢菌(Curvularia clavata)，此外还可举出：近缘弯孢霉(C.affinis)、短孢弯孢(C.brachyspora)、番木瓜弯孢霉(C.caricae-papayae)、画眉草弯孢(C.eragrostidis(Cochliobolus eragrostidis))、弯孢霉(C.fallax)、膝曲弯孢(C.geniculata(Cochliobolus geniculatus))、哈氏弯孢(C.harveyi)、月状旋孢腔菌(C.lunata(Cochliobolus lunatus))、卵形弯孢(C.ovoidea)、苍白弯孢霉(C.pallescens)、狼尾草弯孢(C.penniseti)、普瑞斯弯孢(C.prasadii)、管突弯孢霉(C.protuberata)、塞内加尔弯孢霉(C.senegalensis)、唐菖蒲弯孢霉(C.trifolii)、C.tuberculata(Cochliobolustuberculatus)等。此外，作为棒状弯孢菌(Curvularia clavata)，可以举出从株式会社秋田今野商店分售的棒状弯孢菌(Curvularia clavata)BAUA-2787株。棒状弯孢菌(Curvularia clavata)BAUA-2787于2016年12月28日在独立行政法人制品评价技术基盘机构专利微生物保藏中心(NPMD)(邮编292-0818日本国千叶县木更津市上总镰足2-5-8 122号室)进行保藏，保藏编号为NITE BP-02399。

另外，参与该环状肽化合物合成的一组基因，如后述的实施例所示，可以定义为含有10种基因、优选含有9种基因的一组基因。

这10种基因为：O-甲基转移酶基因、非核糖体肽合成酶基因(NRPS基因)、酰胺酶基因、功能未知的基因(2种)、转录因子基因、编码细霉素B抗性蛋白的pmd1基因、吡咯啉-5-羧酸还原酶样基因和α/β水解酶基因。这10种基因中，特别是作为强力参与环状肽化合物合成的基因，也可以将O-甲基转移酶基因、非核糖体肽合成酶基因(NRPS基因)、酰胺酶基因、功能未知的基因(1种)、转录因子基因、编码细霉素B抗性蛋白的pmd1基因、吡咯啉-5-羧酸还原酶样基因和α/β水解酶基因定义为参与该环状肽化合物合成的一组基因。

〔NRPS基因〕

上述一组基因中，NRPS基因编码具有形成该环状肽化合物的基本骨架的功能的NRPS。即，该NRPS形成由以下10个氨基酸组成的肽骨架：[丙氨酸(Ala)-哌啶酸(Pip)-缬氨酸(Val)-缬氨酸-天冬氨酸(Asp)-缬氨酸-异亮氨酸(Ile)-甘氨酸(Gly)-缬氨酸-酪氨酸(Tyr)]。即，该NRPS具有以下活性：在丙氨酸的羧基与哌啶酸的氨基之间形成肽键；在该哌啶酸的羧基与缬氨酸的氨基之间形成肽键；在该缬氨酸的羧基与缬氨酸的氨基之间形成肽键；在该缬氨酸的羧基与天冬氨酸的氨基之间形成肽键；在该天冬氨酸的羧基与缬氨酸的氨基之间形成肽键；在该缬氨酸的羧基与异亮氨酸的氨基之间形成肽键；在该异亮氨酸的羧基与甘氨酸的氨基之间形成肽键；在该甘氨酸的羧基与缬氨酸的氨基之间形成肽键；在该缬氨酸的羧基与酪氨酸的氨基之间形成肽键；在该酪氨酸的羧基与上述丙氨酸的氨基之间形成肽键。此外，该NRPS具有以下活性：将哌啶酸与缬氨酸之间的肽键甲基化；将缬氨酸与天冬氨酸之间的肽键甲基化；将天冬氨酸与缬氨酸之间的肽键甲基化；将缬氨酸与异亮氨酸之间的肽键甲基化；将甘氨酸与缬氨酸之间的肽键甲基化。

该NRPS具有10个模块，对应于组成上述基本肽骨架[丙氨酸-哌啶酸-缬氨酸-缬氨酸-天冬氨酸-缬氨酸-异亮氨酸-甘氨酸-缬氨酸-酪氨酸]的10个氨基酸。各模块具有A结构域(腺苷酰化结构域：adenylation domain)，其识别目的氨基酸并使氨基酸和AMP(单磷酸腺苷)结合而合成氨酰AMP。此外，各模块具有PCP结构域(肽基载体蛋白结构域：peptidylcarrier protein domain)，其具有磷酸泛酰巯基乙胺，并通过磷酸泛酰巯基乙胺的丝氨酸部位与氨酰AMP之间形成的硫酯来结合该氨酰AMP。另外，各模块具有C结构域(缩合结构域：condensation domain)，其在与相邻的PCP结构域结合的氨酰AMP之间形成肽键。再者，有的模块也具有将形成的肽键甲基化的nMT结构域(N-甲基转移酶结构域：N-methyltransferase domain)。

具有上述活性的NRPS如图1所示，由第一模块～第十模块组成。本文中，NRPS各模块的位置与组成合成的肽骨架的氨基酸的位置一致。此外，具有nMT结构域的模块的位置与N-甲基化的肽键的位置一致。

第一模块从N末端侧起依次具有：由SEQ ID NO:1所示的氨基酸序列组成的第一A结构域、由SEQ ID NO:2所示的氨基酸序列组成的第一PCP结构域。其中，第一模块中的第一A结构域和第一PCP结构域各自并不限于SEQ ID NO:1和SEQ ID NO:2所示的氨基酸序列，如果分别作为A结构域和PCP结构域发挥功能，则也可以是与SEQ ID NO:1和SEQ ID NO:2所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

第二模块从N末端侧起依次具有：由SEQ ID NO:3所示的氨基酸序列组成的第一C结构域、由SEQ ID NO:4所示的氨基酸序列组成的第二A结构域、由SEQ ID NO:5所示的氨基酸序列组成的第二PCP结构域。其中，第二模块中的第一C结构域、第二A结构域和第二PCP结构域各自并不限于SEQ ID NO:3、SEQ ID NO:4和SEQ ID NO:5所示的氨基酸序列，如果分别作为C结构域、A结构域和PCP结构域发挥功能，则也可以是与SEQ ID NO:3、SEQ ID NO:4和SEQ ID NO:5所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

第三模块从N末端侧起依次具有：由SEQ ID NO:6所示的氨基酸序列组成的第二C结构域、由SEQ ID NO:7所示的氨基酸序列组成的第三A结构域、由SEQ ID NO:8所示的氨基酸序列组成的第一nMT结构域、由SEQ ID NO:9所示的氨基酸序列组成的第三PCP结构域。其中，第三模块中的第二C结构域、第三A结构域、第一nMT结构域和第三PCP结构域各自并不限于SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8和SEQ ID NO:9所示的氨基酸序列，如果分别作为C结构域、A结构域、nMT结构域和PCP结构域发挥功能，则也可以是与SEQ ID NO:6、SEQ IDNO:7、SEQ ID NO:8和SEQ ID NO:9所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

第四模块从N末端侧起依次具有：由SEQ ID NO:10所示的氨基酸序列组成的第三C结构域、由SEQ ID NO:11组成的第四A结构域、由SEQ ID NO:12所示的氨基酸序列组成的第四PCP结构域。其中，第四模块中的第三C结构域、第四A结构域和第四PCP结构域各自并不限于SEQ ID NO:10、SEQ ID NO:11和SEQ ID NO:12所示的氨基酸序列，如果分别作为C结构域、A结构域和PCP结构域发挥功能，则也可以是与SEQ ID NO:10、SEQ ID NO:11和SEQ IDNO:12所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

第五模块从N末端侧起依次具有：由SEQ ID NO:13所示的氨基酸序列组成的第四C结构域、由SEQ ID NO:14所示的氨基酸序列组成的第五A结构域、由SEQ ID NO:15所示的氨基酸序列组成的第二nMT结构域、由SEQ ID NO:16所示的氨基酸序列组成的第五PCP结构域。其中，第五模块中的第四C结构域、第五A结构域、第二nMT结构域和第五PCP结构域各自并不限于SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15和SEQ ID NO:16所示的氨基酸序列，如果分别作为C结构域、A结构域、nMT结构域和PCP结构域发挥功能，则也可以是与SEQ IDNO:13、SEQ ID NO:14、SEQ ID NO:15和SEQ ID NO:16所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

第六模块从N末端侧起依次具有：由SEQ ID NO:17所示的氨基酸序列组成的第五C结构域、由SEQ ID NO:18所示的氨基酸序列组成的第六A结构域、由SEQ ID NO:19所示的氨基酸序列组成的第三nMT结构域、由SEQ ID NO:20所示的氨基酸序列组成的第六PCP结构域。其中，第六模块中的第五C结构域、第六A结构域、第三nMT结构域和第六PCP结构域各自并不限于SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19和SEQ ID NO:20所示的氨基酸序列，如果分别作为C结构域、A结构域、nMT结构域和PCP结构域发挥功能，则也可以是与SEQ IDNO:17、SEQ ID NO:18、SEQ ID NO:19和SEQ ID NO:20所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

第七模块从N末端侧起依次具有：由SEQ ID NO:21所示的氨基酸序列组成的第六C结构域、由SEQ ID NO:22所示的氨基酸序列组成的第七A结构域、由SEQ ID NO:23所示的氨基酸序列组成的第四nMT结构域、由SEQ ID NO:24所示的氨基酸序列组成的第七PCP结构域。其中，第七模块中的第六C结构域、第七A结构域、第四nMT结构域和第七PCP结构域各自并不限于SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23和SEQ ID NO:24所示的氨基酸序列，如果分别作为C结构域、A结构域、nMT结构域和PCP结构域发挥功能，则也可以是与SEQ IDNO:21、SEQ ID NO:22、SEQ ID NO:23和SEQ ID NO:24所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

第八模块从N末端侧起依次具有：由SEQ ID NO:25所示的氨基酸序列组成的第七C结构域、由SEQ ID NO:26组成的第八A结构域、由SEQ ID NO:27所示的氨基酸序列组成的第八PCP结构域。其中，第八模块中的第七C结构域、第八A结构域和第八PCP结构域各自并不限于SEQ ID NO:25、SEQ ID NO:26和SEQ ID NO:27所示的氨基酸序列，如果分别作为C结构域、A结构域和PCP结构域发挥功能，则也可以是与SEQ ID NO:25、SEQ ID NO:26和SEQ IDNO:27所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

第九模块从N末端侧起依次具有：由SEQ ID NO:28所示的氨基酸序列组成的第八C结构域、由SEQ ID NO:29所示的氨基酸序列组成的第九A结构域、由SEQ ID NO:30所示的氨基酸序列组成的第五nMT结构域、由SEQ ID NO:31所示的氨基酸序列组成的第九PCP结构域。其中，第九模块中的第八C结构域、第九A结构域、第五nMT结构域和第九PCP结构域各自并不限于SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30和SEQ ID NO:31所示的氨基酸序列，如果分别作为C结构域、A结构域、nMT结构域和PCP结构域发挥功能，则也可以是与SEQ IDNO:28、SEQ ID NO:29、SEQ ID NO:30和SEQ ID NO:31所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

第十模块从N末端侧起依次具有：由SEQ ID NO:32所示的氨基酸序列组成的第九C结构域、由SEQ ID NO:33组成的第十A结构域、由SEQ ID NO:34所示的氨基酸序列组成的第十PCP结构域、由SEQ ID NO:35所示的氨基酸序列组成的第十C结构域。其中，第十模块中的第九C结构域、第十A结构域、第十PCP结构域和第十C结构域各自并不限于SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34和SEQ ID NO:35所示的氨基酸序列，如果分别作为C结构域、A结构域、PCP结构域和C结构域发挥功能，则也可以是与SEQ ID NO:32、SEQ ID NO:33、SEQID NO:34和SEQ ID NO:35所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列。

然而，当第一A结构域与SEQ ID NO:1的氨基酸序列不同时，其是否可以作为对应于丙氨酸的A结构域发挥功能可以如下进行评价。首先，设计突变体NRPS基因以编码第一突变体A结构域，所述第一突变体A结构域被设计为与SEQ ID NO:1的氨基酸序列不同。在适当的宿主内表达该突变体NRPS基因，确认在宿主内和培养上清液中的代谢物中是否合成有具有上述环状肽化合物基本肽骨架的化合物。如果代谢物中合成有具有上述环状肽化合物基本肽骨架的化合物，则设计的第一突变体A结构域可以被评价为作为与丙氨酸相对应的A结构域发挥了功能。予以说明，当第二A结构域至第十A结构域与SEQ ID NO:4、SEQ ID NO:7、SEQ ID NO:11、SEQ ID NO:14、SEQ ID NO:18、SEQ ID NO:22、SEQ ID NO:26、SEQ ID NO:29和SEQ ID NO:33的氨基酸序列不同时，也可以同样地评价其是否可以作为A结构域发挥功能。

另外，当第一PCP结构域与SEQ ID NO:2的氨基酸序列不同时，其是否可以作为PCP结构域发挥功能可以如下进行评价。首先，设计突变体NRPS基因以编码第一突变体PCP结构域，所述第一突变体PCP结构域被设计为与SEQ ID NO:2的氨基酸序列不同。在适当的宿主内表达该突变体NRPS基因，确认在宿主内和培养上清液中的代谢物中是否合成有具有上述环状肽化合物基本肽骨架的化合物。如果代谢物中合成有具有上述环状肽化合物基本肽骨架的化合物，则设计的第一突变体PCP结构域可以被评价为作为PCP结构域发挥了功能。予以说明，当第二PCP结构域至第十PCP结构域与SEQ ID NO:5、SEQ ID NO:9、SEQ ID NO:12、SEQ ID NO:16、SEQ ID NO:20、SEQ ID NO:24、SEQ ID NO:27、SEQ ID NO:31和SEQ ID NO:34的氨基酸序列不同时，也可以同样地评价其是否可以作为PCP结构域发挥功能。

另外，当第一C结构域与SEQ ID NO:3的氨基酸序列不同时，其是否可以作为C结构域发挥功能可以如下进行评价。首先，设计突变体NRPS基因以编码第一突变体C结构域，所述第一突变体C结构域被设计为与SEQ ID NO:3的氨基酸序列不同。在适当的宿主内表达该突变体NRPS基因，确认在宿主内和培养上清液中的代谢物中是否合成有具有上述环状肽化合物基本肽骨架的化合物。如果代谢物中合成有具有上述环状肽化合物基本肽骨架的化合物，则设计的第一突变体C结构域可以被评价为作为C结构域发挥了功能。予以说明，当第二C结构域至第十C结构域与SEQ ID NO:6、SEQ ID NO:10、SEQ ID NO:13、SEQ ID NO:17、SEQID NO:21、SEQ ID NO:25、SEQ ID NO:28、SEQ ID NO:32和SEQ ID NO:35的氨基酸序列不同时，也可以同样地评价其是否可以作为C结构域发挥功能。

再者，当第一nMT结构域与SEQ ID NO:8的氨基酸序列不同时，其是否可以作为nMT结构域发挥功能可以如下进行评价。首先，设计突变体NRPS基因以编码第一突变体nMT结构域，所述第一突变体nMT结构域被设计为与SEQ ID NO:8的氨基酸序列不同。在适当的宿主内表达该突变体NRPS基因，确认在宿主内和培养上清液中的代谢物中是否合成有具有上述环状肽化合物基本肽骨架的化合物。如果代谢物中合成有具有上述环状肽化合物基本肽骨架的化合物，则设计的第一突变体nMT结构域可以被评价为作为nMT结构域发挥了功能。予以说明，当第二nMT结构域至第五nMT结构域与SEQ ID NO:15、SEQ ID NO:19、SEQ ID NO:23和SEQ ID NO:30的氨基酸序列不同时，也可以同样地评价其是否可以作为nMT结构域发挥功能。

如上所述，合成上述环状肽化合物基本肽骨架的NRPS可以由第一模块至第十模块定义。作为一个示例，将如下NRPS的氨基酸序列示于SEQ ID NO:37，所述NRPS来源于棒状弯孢菌(Curvularia clavata)且具有上述环状肽化合物基本肽骨架的合成活性；将与SEQ IDNO:37所示的氨基酸序列相对应的编码区碱基序列示于SEQ ID NO:36。

因此，本发明的NRPS基因可以是编码如下蛋白质的基因，所述蛋白质具有由上述SEQ ID NO:1～SEQ ID NO:35所示的氨基酸序列定义的第一模块至第十模块，并且与SEQID NO:37所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列且具有上述环状肽化合物基本肽骨架的合成活性。氨基酸序列之间的同一性数值可以通过安装有BLAST算法的BLASTN和BLASTX程序来计算(默认设置)。予以说明，同一性数值的计算是在对一对氨基酸序列进行双序列比对分析时计算完全一致的氨基酸残基，作为比较的全部氨基酸残基中的比例。

另外，本发明的NRPS基因也可以是编码如下蛋白质的基因，所述蛋白质具有由上述SEQ ID NO:1～SEQ ID NO:35所示的氨基酸序列定义的第一模块至第十模块，并且具有相对于SEQ ID NO:37的氨基酸序列置换、缺失、插入或增添1个或更多个氨基酸而成的氨基酸序列且具有上述环状肽化合物基本肽骨架的合成活性。本文中，“更多个”例如是指2～1300个，优选为2～1000个，更优选为2～700个，进一步优选为2～500个，进一步优选为2～250个，进一步优选为2～100个，进一步优选为2～50个。

另外，本发明的NRPS基因也可以是编码如下蛋白质的基因，所述基因与由SEQ IDNO:36的碱基序列组成的DNA的互补链的全部或部分在严格条件下杂交，并且所述蛋白质具有由上述SEQ ID NO:1～SEQ ID NO:35所示的氨基酸序列定义的第一模块至第十模块，并且具有上述环状肽化合物基本肽骨架的合成活性。本文中所说的“严格条件”是指形成所谓的特异性杂交体而不形成非特异性杂交体的条件，例如可以参考《分子克隆实验指南》(Molecular Cloning：A Laboratory Manual)(第三版)来适当确定。具体而言，严格度的设置可以根据Southern杂交法时的温度和溶液所含的盐浓度，以及Southern杂交法的洗涤步骤时的温度和溶液所含的盐浓度。更详细地，作为严格条件，例如钠浓度为25～500mM，优选为25～300mM；温度为42～68℃，优选为42～65℃。更具体地为5×SSC(83mM NaCl、83mM柠檬酸钠)，温度42℃。

然而，本发明的NRPS基因并不限于编码如下蛋白质的基因，所述蛋白质具有由上述SEQ ID NO:1～SEQ ID NO:35所示的氨基酸序列定义的第一模块至第十模块。如上所述，将如下NRPS的氨基酸序列示于SEQ ID NO:37，所述NRPS来源于棒状弯孢菌(Curvulariaclavata)且具有上述环状肽化合物基本肽骨架的合成活性；将与该氨基酸序列相对应的编码区碱基序列示于SEQ ID NO:36，本发明的NRPS基因也可以由上述SEQ ID NO:36和SEQ IDNO:37定义。

即，本发明的NRPS基因可以作为编码如下蛋白质的基因，所述蛋白质由SEQ IDNO:37所示的氨基酸序列组成。

另外，本发明的NRPS基因也可以是编码如下蛋白质的基因，所述蛋白质与SEQ IDNO:37所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列且具有上述环状肽化合物基本肽骨架的合成活性。与上述相同，氨基酸序列之间的同一性数值可以通过安装有BLAST算法的BLASTN和BLASTX程序来计算(默认设置)。予以说明，与上述相同，同一性数值的计算是在对一对氨基酸序列进行双序列比对分析时计算完全一致的氨基酸残基，作为比较的全部氨基酸残基中的比例。

另外，关于本发明的NRPS基因，可以利用存储有碱基序列信息的公开数据库，来鉴定满足相对于SEQ ID NO:36所示的碱基序列覆盖率高、E值低、同一性数值高的条件的基因。本文中，作为鉴定的基因的条件，可以将覆盖率设为90％以上，优选设为95％以上，更优选设为99％以上。此外，作为鉴定的基因的条件，可以将E值设为1.0e-5以下，优选设为1.0e-15以下，更优选设为0.0。另外，作为鉴定的基因的条件，可以将同一性数值设为70％以上，优选设为75％以上，更优选设为80％以上。被鉴定为满足这些条件的基因的基因，可以被鉴定为是由SEQ ID NO:36的碱基序列组成的NRPS基因的同源基因概率非常高，且与由SEQ ID NO:36的碱基序列组成的NRPS基因同样编码具有上述环状肽化合物基本肽骨架的合成活性的蛋白质的基因。

鉴定的基因是否编码具有上述环状肽化合物基本肽骨架的合成活性的蛋白质可以通过获得具有该基因的微生物，并对该微生物的上述环状肽化合物合成能力进行验证即可。所获得的微生物中的上述环状肽化合物合成能力可以通过如下方式进行验证：培养该微生物，确认培养的菌体内或培养上清液中是否含有上述环状肽化合物。

然而，本发明的NRPS基因如果确定了其碱基序列，则可以通过如下方法制作：化学合成，或者以基因组DNA为模板的PCR，或者将具有该碱基序列的DNA片段作为探针进行杂交。此外，由与SEQ ID NO:36不同的碱基序列组成的基因或者编码与SEQ ID NO:37不同的氨基酸序列的基因也可以通过对由SEQ ID NO:36所示的碱基序列组成的多聚核苷酸进行定点诱变等来进行合成。予以说明，向由SEQ ID NO:36所示的碱基序列组成的多聚核苷酸中导入突变，可以采用Kunkel法、缺口双链体(Gapped duplex)法等公知的方法或以此为基准的方法。例如，使用利用了定点突变诱变法的突变导入用试剂盒(例如Mutant-K(宝生物公司生产)或Mutant-G(宝生物公司生产))等，或者使用宝生物公司的LA PCR体外诱变系列试剂盒进行突变导入。

特别是，本发明的NRPS基因可以从已知产生上述环状肽化合物的微生物中分离。作为一个示例，可以从棒状弯孢菌(Curvularia clavata)中分离NRPS基因(编码SEQ IDNO:37所示的氨基酸序列的NRPS基因)。

另外，本发明的NRPS基因也可利用SEQ ID NO:36所示的碱基序列，概率很高地从棒状弯孢菌(Curvularia clavata)以外的弯孢属(Curvularia)丝状真菌中分离出。即，通过利用将如下多聚核苷酸作为探针的杂交反应，所述多聚核苷酸由选自SEQ ID NO:36所示的碱基序列的连续一部分碱基序列组成，可以从棒状弯孢菌(Curvularia clavata)以外的弯孢属(Curvularia)丝状真菌的基因组或转录产物来源的cDNA中，分离本发明的NRPS基因。予以说明，棒状弯孢菌(Curvularia clavata)以外的弯孢属(Curvularia)丝状真菌既可以是不产生上述环状肽化合物的丝状真菌，也可以是产生上述环状肽化合物的丝状真菌。其原因在于，即使是不产生上述环状肽化合物的弯孢属(Curvularia)丝状真菌，也有可能具有本发明的NRPS基因。

作为棒状弯孢菌(Curvularia clavata)以外的弯孢属(Curvularia)丝状真菌，例如可举出：近缘弯孢霉(C.affinis)、短孢弯孢(C.brachyspora)、番木瓜弯孢霉(C.caricae-papayae)、画眉草弯孢(有性型)(C.eragrostidis(Cochlioboluseragrostidis(Teleomorph)))、弯孢霉(C.fallax)、膝曲弯孢(有性型)(C.geniculata(Cochliobolus geniculatus(Teleomorph)))、哈氏弯孢(C.harveyi)、月状旋孢腔菌(有性型)(C.lunata(Cochliobolus lunatus(Teleomorph)))、卵形弯孢(C.ovoidea)、苍白弯孢霉(C.pallescens)、狼尾草弯孢(C.penniseti)、普瑞斯弯孢(C.prasadii)、管突弯孢霉(C.protuberata)、塞内加尔弯孢霉(C.senegalensis)、唐菖蒲弯孢霉(C.trifolii)和C.tuberculata(Cochliobolus tuberculatus(有性型))等。

〔弯孢属(Curvularia)丝状真菌〕

本发明的弯孢属(Curvularia)丝状真菌具有以下特征：其具有上述NRPS基因。如上所述，本发明的NRPS基因也能够概率很高地从棒状弯孢菌(Curvularia clavata)以外的弯孢属(Curvularia)丝状真菌中分离出。即，本发明的弯孢属(Curvularia)丝状真菌并不限于棒状弯孢菌(Curvularia clavata)，也可举出以下产生环状肽化合物的菌体：近缘弯孢霉(C.affinis)、短孢弯孢(C.brachyspora)、番木瓜弯孢霉(C.caricae-papayae)、画眉草弯孢(C.eragrostidis(Cochliobolus eragrostidis))、弯孢霉(C.fallax)、膝曲弯孢(C.geniculata(Cochliobolus geniculatus))、哈氏弯孢(C.harveyi)、月状旋孢腔菌(C.lunata(Cochliobolus lunatus))、卵形弯孢(C.ovoidea)、苍白弯孢霉(C.pallescens)、狼尾草弯孢(C.penniseti)、普瑞斯弯孢(C.prasadii)、管突弯孢霉(C.protuberata)、塞内加尔弯孢霉(C.senegalensis)、唐菖蒲弯孢霉(C.trifolii)、C.tuberculata(Cochliobolus tuberculatus)等。

特别是作为本发明的弯孢属(Curvularia)丝状真菌，优选为棒状弯孢菌(Curvularia clavata)。此外，作为本发明的弯孢属(Curvularia)丝状真菌，可以举出从株式会社秋田今野商店分售的棒状弯孢菌(Curvularia clavata)BAUA-2787株。棒状弯孢菌(Curvularia clavata)BAUA-2787于2016年12月28日在独立行政法人制品评价技术基盘机构专利微生物保藏中心(NPMD)(邮编292-0818日本国千叶县木更津市上总镰足2-5-8 122号室)进行保藏，保藏编号为NITE BP-02399。

〔转录因子基因〕

上述参与环状肽化合物合成的一组基因中所含有的转录因子基因编码以下蛋白质，所述蛋白质具有在转录水平正向调控该一组基因中所含有的各基因表达的功能。关于本发明的转录因子基因，作为一个示例，将来源于棒状弯孢菌(Curvularia clavata)且对参与环状肽化合物合成的一组基因中所含有的基因具有转录促进活性的蛋白质的氨基酸序列示于SEQ ID NO:39，将与该氨基酸序列相对应的编码区碱基序列示于SEQ ID NO:38。本发明的转录因子基因可以由上述SEQ ID NO:38和SEQ ID NO:39定义。

即，本发明的转录因子基因可以为编码如下蛋白质的基因，所述蛋白质由SEQ IDNO:39所示的氨基酸序列组成。

另外，本发明的转录因子基因也可以是编码如下蛋白质的基因，所述蛋白质与SEQID NO:39所示的氨基酸序列具有70％以上同一性、优选80％以上同一性、更优选90％以上同一性、进一步优选95％以上同一性、最优选97％以上同一性的氨基酸序列且具有上述转录促进活性。与上述相同，氨基酸序列之间的同一性数值可以通过安装有BLAST算法的BLASTN和BLASTX程序来计算(默认设置)。予以说明，与上述相同，同一性数值的计算是在对一对氨基酸序列进行双序列比对分析时计算完全一致的氨基酸残基，作为比较的全部氨基酸残基中的比例。

另外，本发明的转录因子基因也可以是编码如下蛋白质的基因，所述蛋白质具有相对于SEQ ID NO:39的氨基酸序列置换、缺失、插入或增添1个或更多个氨基酸而成的氨基酸序列且具有上述转录促进活性。本文中，与上述相同，“更多个”例如是指2～40个，优选为2～30个，更优选为2～20个，进一步优选为2～10个，进一步优选为2～5个。

另外，本发明的转录因子基因也可以是编码如下蛋白质的基因，所述基因与由SEQID NO:38的碱基序列组成的DNA的互补链的全部或部分在严格条件下杂交，且所述蛋白质具有上述转录促进活性。本文中所说的“严格条件”与上述相同，是指形成所谓的特异性杂交体而不形成非特异性杂交体的条件，例如可以参考《分子克隆实验指南》(MolecularCloning：A Laboratory Manual)(第三版)来适当确定。具体而言，与上述相同，严格度的设置可以根据Southern杂交法时的温度和溶液所含的盐浓度，以及Southern杂交法的洗涤步骤时的温度和溶液所含的盐浓度。更详细地，作为严格条件，例如钠浓度为25～500mM，优选为25～300mM；温度为42～68℃，优选为42～65℃。更具体地为5×SSC(83mM NaCl、83mM柠檬酸钠)，温度42℃。

如上所述，由与SEQ ID NO:38不同的碱基序列组成的基因，或者编码与SEQ IDNO:39不同的氨基酸序列的基因是否编码具转录促进活性的蛋白质，可以通过如下方式进行确认：将该基因可表达地导入产生上述环状肽化合物的宿主(作为一个示例，为棒状弯孢菌(Curvularia clavata))中，在转录水平验证该宿主中参与环状肽化合物合成的一组基因的表达。

然而，本发明的转录因子基因如果确定了其碱基序列，则可以通过如下方法制作：化学合成，或者以基因组DNA为模板的PCR，或者将具有该碱基序列的DNA片段作为探针进行杂交。此外，由与SEQ ID NO:38不同的碱基序列组成的基因或者编码与SEQ ID NO:39不同的氨基酸序列的基因也可以通过对由SEQ ID NO:38所示的碱基序列组成的多聚核苷酸进行定点诱变等来进行合成。予以说明，向由SEQ ID NO:38所示的碱基序列组成的多聚核苷酸中导入突变，可以采用Kunkel法、缺口双链体(Gapped duplex)法等公知的方法或以此为基准的方法。例如，使用利用了定点突变诱变法的突变导入用试剂盒(例如Mutant-K(宝生物公司生产)或Mutant-G(宝生物公司生产))等，或者使用宝生物公司的LA PCR体外诱变变(LA PCR in vitro Mutagenesis)系列试剂盒进行突变导入。

特别是，本发明的转录因子基因可以从已知产生上述环状肽化合物的微生物中分离。作为一个示例，可以从棒状弯孢菌(Curvularia clavata)中分离转录因子基因(编码SEQ ID NO:39所示的氨基酸序列的转录因子基因)。

另外，本发明的转录因子基因也可利用SEQ ID NO:38所示的碱基序列，概率很高地从棒状弯孢菌(Curvularia clavata)以外的弯孢属(Curvularia)丝状真菌中分离出。即，通过利用将如下多聚核苷酸作为探针的杂交反应，所述多聚核苷酸由选自SEQ ID NO:38所示的碱基序列的连续一部分碱基序列组成，可以从棒状弯孢菌(Curvularia clavata)以外的弯孢属(Curvularia)丝状真菌的基因组或转录产物来源的cDNA中，分离本发明的转录因子基因。予以说明，棒状弯孢菌(Curvularia clavata)以外的弯孢属(Curvularia)丝状真菌既可以是不产生上述环状肽化合物的丝状真菌，也可以是产生上述环状肽化合物的丝状真菌。其原因在于，即使是不产生上述环状肽化合物的弯孢属(Curvularia)丝状真菌，也有可能具有本发明的NRPS基因。

〔转化体〕

在上述本发明的环状肽化合物合成相关基因中，可以通过将NRPS基因导入宿主中并使之可表达，从而制作能够合成具有上述环状肽化合物的基本肽骨架的化合物的转化体，此外可以通过同时将NRPS基因和NRPS基因以外的环状肽化合物合成基因导入宿主中并使之可表达，从而制作具有上述环状肽化合物合成能力的转化体。

本文中，在制作具有上述环状肽化合物合成能力的转化体时，作为NRPS基因以外的环状肽化合物合成相关基因，既可以导入也可以不导入上述转录因子基因。例如，在配置在能够在宿主中发挥功能的持续表达启动子下游的状态下，将NRPS基因和其他基因导入宿主中，由此能够持续对这些NRPS基因和其他基因进行表达诱导。这种情况下，即使不导入上述转录因子基因，环状肽化合物合成相关基因也能够进行表达并产生上述环状肽化合物。

本文中，作为宿主没有特别限制，任何生物，特别是任何微生物都可作为宿主。可用作宿主的微生物没有特别限制，例如可举出：属于大肠杆菌(Escherichia coli)等埃希氏菌属、谷氨酸棒状杆菌(Corynebacterium glutamicum)等棒状菌、枯草芽孢杆菌(Bacillus subtilis)等杆菌属、恶臭假单胞菌(Pseudomonas putida)等假单胞菌属、苜蓿根瘤菌(Rhizobium meliloti)等根瘤菌属的细菌，还可举出：包括酿酒酵母(Saccharomyces cerevisiae)、粟酒裂殖酵母菌(Schizosaccharomyces pombe)、巴斯德毕赤酵母(Pichia pastoris)等酵母、丝状真菌等的真菌。

在以大肠杆菌等细菌作为宿主时，表达载体优选可在该细菌中自主复制，并且由启动子、核糖体结合序列、上述基因、转录终止序列组成。此外，表达载体中也可以含有调控启动子活性的基因。

作为启动子，只要能在大肠杆菌等宿主中表达，则可使用任何启动子。例如可以使用trp启动子、lac启动子、PL启动子、PR启动子等来源于大肠杆菌的启动子，以及T7启动子等来源于噬菌体的启动子。此外，还可以使用tac启动子等人工设计改变的启动子。

作为表达载体的导入方法，只要是将DNA导入细菌的方法，则没有特别限制。例如可举出：使用钙离子的方法[Cohen,S.N.,et al.:Proc.Natl.Acad.Sci.,USA,69:2110-2114(1972)]、电穿孔法等。

另外，作为可用作宿主的酵母没有特别限制，可举出：休哈塔假丝酵母(CandidaShehatae)等念珠菌属(Candida)酵母、树干毕赤酵母(Pichia stipitis)等毕赤酵母属(Pichia)酵母、嗜鞣管囊酵母(Pachysolen tannophilus)等管囊酵母属(Pachysolen)酵母、酿酒酵母(Saccharomyces cerevisiae)等酵母属(Saccharomyces)酵母和粟酒裂殖酵母菌(Schizosaccharomyces pombe)等裂殖酵母属(Schizosaccharomyces)酵母，特别优选为酿酒酵母(Saccharomyces cerevisiae)。

另外，在增强上述NRPS基因和其他基因的表达时，使用高转录活性的适当启动子。作为这种启动子没有特别限制，例如可以利用甘油醛-3-磷酸脱氢酶基因(TDH3)的启动子、3-磷酸甘油酸激酶基因(PGK1)的启动子、高渗透压应答7基因(HOR7)的启动子等。其中，优选丙酮酸脱羧酶基因(PDC1)的启动子，因其高表达下游目的基因的能力高。此外，可以通过使用gal1启动子、gal10启动子、热休克蛋白启动子、MFα1启动子、PHO5启动子、GAP启动子、ADH启动子、AOX1启动子等，来高表达下游基因。

另外，作为可用于宿主的丝状真菌没有特别限制，可举出：构巢曲霉(Aspergillusnidulans)、黑曲霉(Aspergillus niger)、米曲霉(Aspergillus oryzae)、酱油曲霉(Aspergillus sojae)、灰绿曲霉(Aspergillus glaucus)等曲霉属(Aspergillus)丝状真菌；里氏木霉(Trichoderma reesei)、绿色木霉(Trichoderma viride)等木霉属(Trichoderma)丝状真菌；微小根毛霉(Rhizomucor pusillus)、米赫根毛霉(Rhizomucormiehei)等根毛霉属(Rhizomucor)丝状真菌；特异青霉(Penicillium notatum)、产黄青霉(Penicillium chrysogenum)等青霉菌属(Penicillium)丝状真菌；米根霉(Rhizopusoryzae)等根霉属菌(Rhizopus)丝状真菌；Acremonium cellulolyticus；灰腐质霉(Humicola grisea)；嗜热子囊菌(Thermoaseus aurantiacus)。特别是，作为宿主，优选曲霉属(Aspergillus)丝状真菌，特别优选米曲霉(Aspergillus oryzae)。

在丝状真菌中表达上述NRPS基因和其他基因时，可以使用：α-淀粉酶基因(amyB)的启动子、α-葡萄糖苷酶基因(agdA)的启动子、葡糖淀粉酶基因(glaA)的启动子、色氨酸生物合成基因(trpC)的启动子、醇脱氢酶基因(alcA)的启动子、翻译延伸因子基因(tef1)的启动子、丙糖磷酸异构酶基因(tpiA)的启动子、甘油醛-3-磷酸脱氢酶(gpdA)基因的启动子、烯醇化酶(enoA)的启动子、丙酮酸羧化酶(pdcA)的启动子、纤维二糖水解酶基因(cbh1)的启动子等。

另外，作为导入上述基因的方法，也可应用作为酵母和丝状真菌的转化方法而已知的现有公知的任何方法。具体而言，可以使用转化法、转染法、接合法、原生质体法、原生质球法、电穿孔法、脂转染法、醋酸锂法等。

〔环状肽化合物的制造〕

通过利用上述转化体，可以制造目的环状肽化合物。

即，在上述本发明的环状肽化合物合成相关基因中，通过利用导入有NRPS基因并使之可表达的转化体，可以制造具有上述环状肽化合物基本肽骨架的化合物。例如，通过化学合成反应，可以从得到的化合物制造上述环状肽化合物。此外，通过利用导入有NRPS基因和其他基因并使之可表达的转化体，可以制造上述环状肽化合物。

用转化体合成的上述环状肽化合物和具有其基本肽骨架的化合物可利用离心分离机、Miracloth滤布等从培养上清液中分离菌体后，加入乙酸乙酯等有机溶剂进行提取。此外，通过物理破坏法(均化器、玻璃微珠破碎、冻融等)和化学破坏法(溶剂处理、酸碱处理、渗透压处理、酶处理等)使其从菌体内释放到菌体外后，可以加入乙酸乙酯等有机溶剂进行提取。关于提取的上述环状肽化合物和具有其基本肽骨架的化合物的纯化，可以通过现有的纯化方法(柱色谱法、盐析沉淀等)来进行。这些方法可以根据需要而适当地组合进行。

如上制造的上述环状肽化合物，例如可以用作对植物病原菌尤其是真菌类具有杀菌作用的杀菌剂。更具体地，在将上述环状肽化合物用作杀菌剂时，可以直接使用，通常也可以将其与适当的固体载体、液体载体等、表面活性剂及其他制剂用辅助剂混合制成以下剂型进行使用：乳剂、水乳剂(EW剂)、液剂、悬浮剂、可湿性粉剂、水分散颗粒剂、粉剂、无飘移粉剂(DL粉剂)、微粒剂、微粒剂F、粒剂、片剂、油剂、气雾剂、可流动性制剂、干燥可流动性制剂、微囊剂等任意剂型。

作为固体载体，例如可举出：淀粉、活性炭、大豆粉、小麦粉、木粉、鱼粉、奶粉等动植物性粉末；滑石、高岭土、膨润土、碳酸钙、沸石、硅藻土、白炭墨、粘土、氧化铝、硫酸铵、尿素等无机物粉末。

作为液体载体，例如可举出：水；异丙醇、乙二醇等醇类；环己酮、甲乙酮等酮类；二噁烷、四氢呋喃等醚类；煤油、轻油等脂肪族烃类；二甲苯、三甲苯、四甲苯、甲基萘、溶剂石脑油等芳香族烃类；氯苯等卤代烃类；二甲基乙酰胺等酸酰胺类；脂肪酸的甘油酯等酯类；乙腈等腈类；二甲基亚砜等含硫化合物类等。

作为表面活性剂，例如可举出：烷基苯磺酸金属盐、二萘基甲烷二砜酸金属盐、醇硫酸酯盐、烷基芳基磺酸盐、木质素磺酸盐、聚氧乙烯二醇醚、聚氧乙烯烷基芳基醚、聚氧乙烯脱水山梨糖醇单烷基化物等。

作为其他辅助剂，例如可以使用：羧甲基纤维素、阿拉伯树胶、海藻酸钠、瓜尔胶、黄蓍胶、聚乙烯醇等粘合剂或增稠剂；金属皂等消泡剂；脂肪酸、烷基磷酸盐、有机硅、石蜡等物理性质提高剂；着色剂等。

杀菌剂的各种制剂或其稀释物的施用通常可以通过普遍进行的施用方法来进行，即：散布(例如喷雾、起雾、雾化、撒粉、撒粒、水施用、箱施用等)、土壤施用(例如混入、灌注等)、表面施用(例如涂布、粉剂包衣、包覆等)、浸渍、毒饵、熏烟施用等。此外，也可以通过所谓的超高浓度少量散布法来施用。该方法中，可以含有100％的活性成分。

另外，有效成分为上述环状肽化合物的杀菌剂，即使有效成分单独为上述环状肽化合物，不言而喻也十分有效，根据需要，也可以混用和同时使用其他肥料、农药，例如杀虫剂、杀螨剂、杀线虫剂、其他杀菌剂、抗病毒剂、引诱剂、除草剂、植物生长调节剂等，这种情况下，有时会显示出更优异的效果。作为KK-1自身表现出防除效果的植物病原菌，例如可举出但不限于：灰霉病菌(Botrytis cinerea)、小麦白粉病菌(Blumeria graminis)、稻瘟病菌(Magnaporthe oryzae)、水稻纹枯病菌(Thanatephorus cucumeris(Frank)Donk)等。

实施例

下面通过实施例进一步详细地说明本发明，但本发明的技术范围并不限于以下实施例。

〔实施例1〕

[棒状弯孢菌(Curvularia clavata)的基因组分析]

将从株式会社秋田今野商店分售的棒状弯孢菌(C.clavata)BAUA-2787株的分生孢子接种于200ml的CM液体培养基(500ml厄伦美厄烧瓶)，在26℃、130rpm下培养48小时。用Miracloth滤布收集培养的菌体后，用刮匙按压菌体进行脱水，将菌体放入预冷至-20℃的研钵中，注入液氮使其冷冻。用研杵快速研磨成粉状后，使用DNeasy Plant Maxi Kit试剂盒提取基因组DNA。

利用两种下一代测序仪(5500xl SOLiD(LifeTechnologies)和MiSeq(Illumina))进行基因组分析。使用5500SOLiD Mate-Paired Library Kit试剂盒(用于5500xl SOLiD)、Nextera DNA Sample Prep Kit试剂盒(用于MiSeq)，由制备的棒状弯孢菌(C.clavata)基因组DNA制作文库，并通过下一代测序仪进行基因组分析。

[棒状弯孢菌(C.clavata)所具有的NRPS基因的探究]

由棒状弯孢菌(C.clavata)BAUA-2787株产生的环状肽(以下称为KK-1)如图2所示，是由10个氨基酸组成的环状肽，作为其特征可举出：9个肽键中的5个被N-甲基化；以及分子内的酪氨酸(Tyr)残基被O-甲基化。本实施例中，对合成该KK-1的基本骨架的非核糖体肽合成酶(nonribosomal peptide synthetase；NRPS)基因进行了探究。

首先，根据棒状弯孢菌(C.clavata)BAUA-2787株的基因组序列信息，推定生物合成肽的基本骨架的NRPS基因，以推定KK-1的生物合成基因簇。

NRPS是不通过核糖体而将氨基酸连接并合成为肽的酶，具有与组成产物肽的氨基酸残基的数量和顺序一致的模块结构。因此可以推定，具有与化合物的结构特征一致的模块和结构域结构的NRPS是生物合成该化合物的肽骨架的NRPS。

通过棒状弯孢菌(C.clavata)BAUA-2787株的基因组分析，推定出该菌体所具有的基因和被编码的蛋白质的序列，由此从棒状弯孢菌(C.clavata)的基因组中检索所有被推定为编码NRPS的基因，基于这些推定蛋白质的结构特征，来推定生物合成KK-1的肽基本骨架的基因。

首先，通过用近缘丝状真菌异旋孢腔菌(Cochliobolus heterostrophus)NRPS的同源性检索，来探究棒状弯孢菌(C.clavata)的全部NRPS基因。在异旋孢腔菌(C.heterostrophus)中，发现了12个NRPS基因NPS1～NPS12。考察该12个NRPS结构域结构可知，NPS7是与PKS(polyketide synthase，聚酮合酶)的杂合型NRPS，NPS10和NPS12是不具有C结构域的NRPS样蛋白质(NRPS-like protein)。因此，将这三者除外，将NPS1～NPS6、NPS8、NPS9和NPS11的氨基酸序列作为同源性检索的查询序列(query)，对棒状弯孢菌(C.clavata)的推定蛋白质的氨基酸序列的数据库进行blastp检索。关于丝状真菌，考虑到有报告称具有约10个NRPS(异旋孢腔菌(C.heterostrophus)具有12个NRPS，烟曲霉(Asperillus fumigatus)具有14个NRPS)，对于作为查询序列的每个基因，提取检索命中的前20个基因，结果缩小至以下24个基因。

TRAF01000140000154、TRAF01000135000001、TRAF01000070000001、TRAF01000068000001、TRAF01000108000067、TRAF01000130000847、TRAF01000117000049、TRAF01000117000050、TRAF01000099000028、TRAF01000088000002、TRAF01000082000001、TRAF01000081000001、TRAF01000117000368、TRAF01000142000376、TRAF01000109000032、TRAF01000142000383、TRAF01000136000233、TRAF01000100000101、TRAF01000061000021、TRAF01000108000142、TRAF01000139000099、TRAF01000140000122、TRAF01000117000201、TRAF01000136000219。

基于用下一代测序仪分析的基因组DNA序列，使用专用程序来预测棒状弯孢菌(C.clavata)的基因序列(CDS)。但是，该CDS预测的错误并不少，尤其是内含子的存在等经常导致CDS的5’-侧和3’-侧的序列被切除，预测结果比实际的CDS短。为了得到更加准确的CDS，需要利用基因所在的基因组区域周围的序列信息等，逐一详细研究。因此，首先将缩小的24个基因中的每个基因从推定起始密码子上游3000bp到推定终止密码子下游3000bp的基因组DNA序列作为查询序列，对GenBank的数据库进行blastx检索。通过该检索可知与已知蛋白质序列显示出同源性的区域，因此可以推定基因的起始密码子和终止密码子。此外，根据与已知的蛋白质序列的同源性同样表示出了内含子存在的位点，因此可以根据GU-AG规则来预测内含子位点，推定出更加准确的CDS。

结果表明，虽然TRAF01000117000049和TRAF01000117000050被推定为不同的基因，但实际上是1个基因(作为TRAF01000117000049-50)。此外，由于用于检索的基因的周围基因组DNA序列不能充分得到的原因，也存在5’-侧缺失(未找到起始密码子)或3’-侧缺失(未找到终止密码子)的基因。下面给出这些基因。

TRAF01000135000001(5’缺失)

TRAF01000070000001(5’和3’均缺失)

TRAF01000068000001(3’缺失)

TRAF01000088000002(3’缺失)

TRAF01000082000001(5’缺失)

TRAF01000081000001(3’缺失)

TRAF01000117000368(5’缺失)

经过对这些序列进行更加详细的分析，在TRAF01000068000001的3’末端、TRAF01000070000001的5’和3’末端、TRAF01000135000001的5’末端发现2285bp完全相同的序列。即，推定出这三个基因实际上是TRAF01000068000001、TRAF01000070000001和TRAF01000135000001按照这个顺序连接而成的一个基因(作为TRAF01000135000001_J3G)。

另外，在TRAF01000088000002和TRAF01000081000001的3’末端，以及TRAF01000082000001和TRAF01000117000368的5’末端同样发现2959bp完全相同的序列。即，推定出这4个基因实际上是2个基因。其中，这些基因有可能是由以下4组组合连接而成：

1)TRAF01000088000002-TRAF01000082000001；

2)TRAF01000088000002-TRAF01000117000368；

3)TRAF01000081000001-TRAF01000082000001；

4)TRAF01000081000001-TRAF01000117000368。

但是，根据序列信息不能确定正确的组合。

接着，考察进行了CDS预测的基因所编码的蛋白质的结构域结构。该分析使用InterProScan和antiSMASH程序，将通过antiSMASH的分析结果示于图3-1和图3-2。具有作为NRPS的功能所必需的A结构域、PCP结构域、C结构域的基因为TRAF01000140000154、TRAF01000135000001_J3G、TRAF01000108000067、TRAF01000130000847、TRAF01000117000049、TRAF01000117000050、TRAF01000099000028、TRAF01000088000002、TRAF01000082000001、TRAF01000081000001、TRAF01000117000368、TRAF01000142000376、TRAF01000109000032、TRAF01000142000383这14个基因，但如前所述，其中4个基因(TRAF01000088000002、TRAF01000082000001、TRAF01000081000001、TRAF01000117000368)是2个基因被断开而成的，因此表明棒状弯孢菌(C.clavata)BAUA-2787株具有12个NRPS基因。予以说明，通过antiSMASH的分析发现的TRAF01000142000383的结构域只有A结构域和C结构域，而通过InterProScan的分析则在N末端侧发现PCP结构域样的序列，因此推定为NRPS。此外，TRAF01000109000032在N末端侧具有典型的PKS(polyketide synthase，聚酮合酶)结构域，因此认为是PKS-NRPS杂合体。

[参与KK-1生物合成的NRPS的推定]

考虑到棒状弯孢菌(C.clavata)BAUA-2787株具有12个NRPS基因，因此从其中探究生物合成KK-1基本肽骨架的基因。KK-1如图2所示，将由10个氨基酸组成的环状肽作为基本骨架。Tyr和Ala之间不形成肽键而是形成酯键，认为是受到某种修饰而成为这种形式的。通过NRPS生物合成的肽具有如下特征：构成所述肽的氨基酸数与生物合成NRPS的模块数一致。因此认为，生物合成由10个氨基酸组成的KK-1基本肽骨架的NRPS具有10个模块，即10个A结构域。于是对棒状弯孢菌(C.clavata)的12个推定NRPS基因的A结构域数进行了考察，由于只有TRAF01000135000001_J3G具有10个A结构域，因此认为该基因是与KK-1生物合成有关的NRPS(图3-1)。

在TRAF01000135000001_J3G的结构域结构中，如图1所示，存在5个将肽键N-甲基化的N-甲基转移酶结构域(nMT结构域)，位于第三模块、第五模块、第六模块、第七模块和第九模块。NRPS各模块的位置与组成生物合成的肽的氨基酸的位置一致，同样，具有nMT结构域的模块与被N-甲基化的肽键的位置也一致。假设TRAF01000135000001_J3G的第一模块与KK-1的Ala残基相对应，则具有nMT结构域的模块与N-甲基化的肽键的位置完全一致。由此强烈表明，TRAF01000135000001_J3G是生物合成KK-1基本肽骨架的NRPS。

另外，推定通过TRAF01000135000001_J3G合成Ala-Pip-(N-甲基)Val-Val-(N-甲基)Asp-(N-甲基)Val-(N-甲基)Ile-Gly-(N-甲基)Val-Tyr这种肽之后，其被环化和修饰。予以说明，已知在众所周知的来源于细菌的NRPS中，TE结构域负责环化反应。而在丝状真菌中，很多NRPS缺乏TE结构域，取而代之地含有C结构域。近年来，已明确在丝状真菌中该C结构域负责肽的环化。

在TRAF01000135000001_J3G中，第十模块的C末端也具有C结构域，认为该C结构域有可能参与环化。此外，推定通过TRAF01000135000001_J3G生物合成基本肽骨架之后，通过各种酶进行修饰，从而生物合成KK-1。认为这些修饰酶基因与TRAF01000135000001_J3G一起在棒状弯孢菌(C.clavata)BAUA-2787株的基因组中形成基因簇。

将组成推定的NRPS的第一模块至第十模块所含有的各结构域、与其氨基酸序列相关的SEQ ID NO等总结在下表中。

[表1]

予以说明，在表1中，“氨基酸序列”一栏中记载的数值范围表示推定的NRPS的全部氨基酸序列(SEQ ID NO:37)中氨基酸残基的位置。

[KK-1的生物合成基因簇的推定]

如上所述，由于推定TRAF01000135000001_J3G作为形成KK-1基本肽骨架的NRPS基因，由此认为在含有该NRPS(TRAF01000135000001_J3G)的区域中，存在组成KK-1生物合成基因簇的一组基因。因此，关于位于该NRPS周围的基因，基于所编码的蛋白质的氨基酸序列和根据氨基酸序列推定出的功能，尝试推定组成生物合成基因簇的一组基因。予以说明，TRAF01000135000001_J3G是将在基因组测序和基因预测时被断开的3个序列结合而成的，因此在以下的基因簇预测中使用结合后的序列。

首先，在NRPS基因(TRAF01000135000001_J3G)的上游和下游分别提取14个基因，然后对GenBank数据库进行blastp检索，由此对这些基因添加注释。将其结果示于图4。根据该注释，将含有可能参与次级代谢的基因的区域(TRAF01000135000002至TRAF01000068000009)推定为KK-1生物合成基因簇。将该推定生物合成基因簇的结构示意性地示于图5。该簇的大小约为75kb，形成了簇的大部分被NRPS基因所占据的结构。从组成簇的基因的功能来看，TRAF01000135000002被注释为O-甲基转移酶，因此认为它参与KK-1分子内的酪氨酸(Tyr)残基的O-甲基化。注释为编码细霉素B抗性蛋白的pmd1的TRAF01000068000006作为蛋白质的功能为ABC转运体，认为它有可能参与KK-1向菌体外的排出。此外，在簇内存在转录因子基因(TRAF01000068000005)。一般而言，组成生物合成基因簇的基因的表达通常受到存在于簇内的转录因子的共同调控，从而推定在本基因簇中，TRAF01000068000005也调控组成簇的基因整体的转录。因此，认为通过调控该转录因子的表达，可以调控基因簇的表达，从而认为它在尝试实现KK-1的高产生方面是重要基因。

[基于基因表达信息的KK-1的生物合成基因簇的推定]

在进行KK-1生物合成基因簇的推定时，还通过使用MIDDAS-M(Umemura M.et.al.,Plos one,8(5),e63673.(2013))算法的生物信息学方法进行簇检测。

MIDDAS-M基于基因表达信息检测基因簇。在检测次级代谢物的生物合成基因簇时，将产生和不产生该物质的各个条件下的产生宿主的基因的全面表达信息进行比较，将在产生条件下联动起作用的一组基因检测为簇。将基因按照基因组的位置顺序排列在横轴，将得分(表达量)绘制在纵轴，由此以峰的形式检测存在表达量变动的基因聚集的区域。

当将培养温度设为37℃高温时，未在棒状弯孢菌(C.clavata)BAUA-2786株的CM液体培养中确认到KK-1产生，因此将通常培养温度26℃设为产生条件，将37℃设为不产生条件。通过使用下一代DNA测序仪的RNA-seq，对这些条件下的棒状弯孢菌(C.clavata)的基因表达进行全面分析，通过MIDDAS-M检测簇，结果如图6所示，检测到与基于序列信息推定的基因簇相同的一组基因(图6中的a和b)。检测到2个峰的原因如前所述，是因为该基因簇在最初的基因簇序列数据中是被断开的状态。予以说明，同时也在将通过手动相互连接的推定簇序列与基因组序列的末端(横轴右端)结合而成的序列中使用MIDDAS-M进行分析，结果也明显检测到这部分的基因(图6中的c)。

以上结果强烈表明，含有基于基因序列信息推定的10个基因的基因簇参与了KK-1的生物合成。关于推定的基因簇中所含有的10个基因，将编码区域的碱基序列和氨基酸序列总结在下表中。

[表2]

基因ID	碱基序列	氨基酸序列
			TRAF01000135000002	SEQ ID NO：40	SEQ ID NO：41
TRAF01000135000001_J3G	SEQ ID NO：36	SEQ ID NO：37
			TRAF01000068000002	SEQ ID NO：42	SEQ ID NO：43
TRAF01000068000003	SEQ ID NO：44	SEQ ID NO：45
			TRAF01000068000004	SEQ ID NO：46	SEQ ID NO：47
TRAF01000068000005	SEQ ID NO：38	SEQ ID NO：39
			TRAF01000068000006	SEQ ID NO：48	SEQ ID NO：49
TRAF01000068000007	SEQ ID NO：50	SEQ ID NO：51
			TRAF01000068000008	SEQ ID NO：52	SEQ ID NO：53
TRAF01000068000009	SEQ ID NO：54	SEQ ID NO：55

〔实施例2〕

本实施例中，对于实施例1中推定的KK-1生物合成基因簇中所含有的一组基因中的转录因子基因进行功能分析。予以说明，本实施例中，将编码在实施例1中记作TRAF01000068000005的转录因子的基因记作TF068-005。

[使用转录因子高表达株的分析]

1)TF068-005高表达构建体的构建(图7)

将高表达TF068-005基因的构建体示意性地示于图7。该构建体中，从棒状弯孢菌(C.clavata)BAUA-2787株的Ccnmt1(TRAF01000124000183)基因的起始密码子起，将上游1000bp作为启动子，将Ccnmt1基因的下游355bp作为终止子，将金担子素A(AurA)抗性基因作为选择标记。予以说明，Ccnmt1基因的启动子和终止子通过以棒状弯孢菌(C.clavata)基因组DNA为模板的PCR进行扩增；金担子素A(AurA)抗性基因通过以pAUR316质粒(日本宝生物株式会社)为模板的PCR进行扩增；TF068-005基因通过以棒状弯孢菌(C.clavata)的cDNA为模板的PCR进行扩增。

然后，与In-Fusion HD克隆试剂盒(Clontech)的线性pUC19一起进行In-Fusion反应，制作目的质粒(pUC-Pnmt1-TF-Tnmt1-aurA)。所使用的引物和反应条件如下所示：

nmt1-pro_In-Fus_FW1：

5’-cggtacccggggatcTAGTCTGTTGATTACTCG-3’(SEQ ID NO:56)

nmt1-pro_In-Fus_RV1：

5’-ctcgacaaaggtcatTTTGACTTTGAATACCGGTG-3’(SEQ ID NO:57)

nmt1-ter_FW1：

5’-GCAGTTGCCGTTGGACCAGAGG-3’(SEQ ID NO:58)

nmt1-ter_In-Fus_RV2：

5’-atagtcataacaagcCGCGACACTGTAATATTAAAGC-3’(SEQ ID NO:59)

TF-CDS_FW1：

5’-ATGACCTTTGTCGAGACTGTAGCC-3’(SEQ ID NO:60)

TF-CDS_In-Fus_RV1：

5’-TCCAACGGCAACTGCCTATGATATACTCATGTTCTCGTC-3’(SEQ ID NO:61)

PCR使用Phusion Hot Start II高保真DNA聚合酶(赛默飞世尔科技公司)进行。作为温度条件，初始变性：设为98℃30秒；变性：设为98℃10秒；退火：设为60℃30秒；延伸：设为72℃30秒为1个循环，进行30个循环；最终延伸：设为72℃7分钟。

AnaurA-mark_In-Fus_FW1：

5’-cgactctagaggatcCTGATGGTCAGATGGATCTG-3’(SEQ ID NO:62)

AnaurA-mark_RV1：

5’-GCTTGTTATGACTATGTATACATATGCG-3’(SEQ ID NO:63)

PCR使用Phusion Hot Start II高保真DNA聚合酶(赛默飞世尔科技公司)进行。作为温度条件，初始变性：设为98℃30秒；变性：设为98℃10秒；退火：设为60℃30秒；延伸：设为72℃2分钟为1个循环，进行30个循环；最终延伸：设为72℃7分钟。

2)棒状弯孢菌(C.clavata)BAUA-2787株的转化

将棒状弯孢菌(C.clavata)BAUA-2787株的孢子悬浮液接种于100ml的CM培养基中(300ml厄伦美厄烧瓶)，在30℃振荡培养40小时，然后通过使用玻璃过滤器(11G1)过滤来收集菌丝，用无菌水洗涤后，用刮匙等按压以充分除去水分。将菌体加入到10ml的用于原生质体形成的溶液(YL组分)中进行悬浮，在30℃缓慢振荡3小时，以形成原生质体。用Miracloth滤布过滤，以1,500×g离心滤液5分钟，收集原生质体，用0.8M的NaCl洗涤2次。以2×10⁸/ml将原生质体悬浮于溶液1[0.8M NaCl、10mM CaCl2、10mM Tris-HCl(pH值8.0)]中，然后加入0.2体积的溶液2[40％(w/v)PEG4000、50mM CaCl2、50mM Tris-HCl(pH值8.0)]并缓慢悬浮，向0.2ml的原生质体悬浮液中加入pUC-Pnmt1-TF-Tnmt1-aurA(7.8μg/20μl)，在冰中静置10分钟。加入1ml溶液2并缓慢悬浮，在室温静置15分钟。加入10ml溶液1并缓慢悬浮，通过离心收集原生质体，尽量除去上清液，将原生质体悬浮于1ml溶液1中。在5块CM+1.2M蔗糖+10μg/ml AbA筛选平板上各放置0.2ml的原生质体悬浮液，加入6～7ml(每直径90mm的培养皿)的CM+1.2M蔗糖+10μg/ml AbA软琼脂(1％)选择培养基，迅速重叠成多层以使原生质体均匀，在26℃培养6天。

予以说明，使用pUC-Pnmt1-TF-Tnmt1-aurA质粒的棒状弯孢菌(C.clavata)的转化使用两种方法进行：直接使用环状质粒；以及用限制酶BamHI在一个位点处进行切割，以线性状使用。

3)TF068-005高表达株的培养条件

TF068-005高表达株进行以下3组培养，研究RNA的制备和KK-1的产生。

“培养1”

将野生株和TF068-005高表达株的分生孢子接种到100ml的CM培养基(500mL厄伦美厄烧瓶)中，在26℃、160rpm振荡培养72小时。

“培养2”

将野生株和TF068-005高表达株的分生孢子接种到30ml的K1培养基(100mL带挡板的厄伦美厄烧瓶)中，在26℃、200rpm预培养72小时，将500μl培养液转移到将葡萄糖浓度设为5％的CM培养基(500mL带挡板的厄伦美厄烧瓶)中，在26℃、130rpm进行主培养。

“培养3”

向50ml离心管中加入2.5g糙米和2ml水，进行高压灭菌。向其中接种野生株和TF068-005高表达株的分生孢子，在26℃静置培养8天。

4)TF068-005高表达株的RNA-seq分析

用液氮将液体培养的菌体冷冻，用研钵和研杵磨碎，使用ISOGEN(NIPPON GENE)制备总RNA。使用Truseq RNA样品制备试剂盒v2，从该总RNA制备RNA-Seq用文库，用于下一代测序仪(MiSeq)(双末端，读取长度75)。使用TopHat程序将得到的序列数据映射到棒状弯孢菌(C.clavata)的基因组序列。

5)KK-1的提取和定量

在液体培养中，在30ml的培养体系中直接加入15ml乙酸乙酯，以130rpm振荡1小时后，以4,700×g离心15分钟。回收上清液并进行离心浓缩，将其作为菌体外组分。然后，向回收乙酸乙酯后的水层加入15ml丙酮，用涡旋混合器搅拌后，以4,700×g离心15分钟。通过倾析回收上清液，利用离心浓缩除去丙酮。向其中加入15ml乙酸乙酯，以4,700×g离心15分钟。将乙酸乙酯层回收到50ml试管中，将离心浓缩的层作为菌体内组分。

在固体培养中，将25ml的80％丙酮加入到培养体系，进行涡旋混合。利用离心浓缩除去丙酮，加入10ml乙酸乙酯，用涡旋混合器搅拌。通过离心分离回收乙酸乙酯层，将用离心柱纯化的所得物作为样品。

KK-1的定量通过UPLC进行。条件如下所示：

·仪器：ACQUITY UPLC I-Class系统(Waters)

·色谱柱：Acquity UPLC BEH C18 2.1x100mm

·溶剂：梯度50％-98％的乙腈+0.1％甲酸(3分钟)

·流速：0.6ml/分钟

·检测波长：273nm

<结果与讨论>

本实施例中，使用作为在棒状弯孢菌(C.clavata)中高表达的基因而被发现的nmt-1基因同源物(TRAF01000124000183；Ccnmt1)的启动子和终止子，制作使转录因子高表达的构建体(pUC-Pnmt1-TF-Tnmt1-aurA)(图7)。使用该质粒的棒状弯孢菌(C.clavata)的转化使用两种方法进行：直接使用环状质粒；以及在一个位点处进行切割，以线性状使用。对转化后得到的线性导入质粒的1株(ox_TF_1)和环状导入质粒的1株(ox_TF_2)进行RNA-seq分析，并确认KK-1的生产率。

首先，在CM液体培养基中将野生株和TF068-005高表达株(ox_TF_1和ox_TF_2)的分生孢子在26℃、160rpm振荡培养72小时，进行RNA-seq分析(方法“培养1”)。将KK-1生物合成基因簇构成基因的转录水平的研究结果示于图8。如图8所示，在TF068-005高表达株中，所有基因与野生株相比，均确认到约8倍的增加。予以说明，ox_TF_1株和ox_TF_2株的转录没有差别。

因此，研究这些TF068-005高表达株中的KK-1生产率，同时也进行RNA-seq分析。此时，为了使液体培养时的菌体形状稳定，在含有大豆粉(Soybean flour)的K1培养基中进行预培养后，用CM培养基进行主培养(方法“培养2”)。将主培养开始后2天和4天的基因转录通过RNA-seq进行分析，将结果示于图9。如图9所示，TF068-005高表达株的KK-1生物合成基因簇构成基因的转录相比野生株明显更高。此外，与主培养开始后2天相比，主培养开始后4天的TF068-005高表达株与野生株中的表达量的差别更大。

接着，在主培养开始后3天和7天的时刻分成菌体外和菌体内两个方面对KK-1生产量进行研究。将其结果示于图10。如图10所示，在TF068-005高表达株中，培养体系内的KK-1的总量(菌体外+菌体内)在培养3天和7天均有增加，在第7天达到野生株的约2倍。此外，根据图10所示的结果认为，KK-1总量的约20％～30％在菌体内蓄积。

另外，确认了使用糙米在固体培养条件下的KK-1生产率(方法“培养3”)，将其结果示于图11。此外，图11中示出拍摄固体培养TF068-005高表达株时的状态的照片。如图11所示，即使通过固体培养，TF068-005高表达株中KK-1的生产率也达到野生株的约6倍。

由以上结果可知，TF068-005基因的高表达使得推定的基因簇中所含有的各基因的表达量增高。因此，TF068-005基因被鉴定为在转录水平正向调控特定基因表达的转录基因。而且，通过使编码转录因子的TF068-005基因高表达，KK-1的生产率提高，因此表明其表达通过调控该转录因子而提高的一组基因是参与产生KK-1的基因簇。

[使用转录因子破坏株的分析]

1)CcpyrG基因破坏用质粒的构建(图12)

将用于破坏棒状弯孢菌(C.clavata)BAUA-2787株中的pyrG基因(CcpyrG基因)的质粒的构建方案示于图12。予以说明，pyrG基因破坏株不能将5-氟乳清酸(5-FOA)转变为5-氟尿苷磷酸(胸腺嘧啶生物合成酶的抑制剂)，因此在含有5-FOA的培养基中也能生长。

首先，如图12所示，以棒状弯孢菌(C.clavata)BAUA-2787株的基因组DNA为模板，利用以下引物组进行PCR，对CcpyrG基因的起始密码子的上游2005bp至终止密码子的下游1261bp进行扩增。

CcPyrG-del_FW3：

5’-GACAGACTCTTCGTCGACGTC-3’(SEQ ID NO:64)

CcPyrG-del_RV3：

5’-GTTGTGGTTGGTGTTCCTGAGG-3’(SEQ ID NO:65)

PCR使用Phusion Hot Start II高保真DNA聚合酶(赛默飞世尔科技公司)进行。温度条件如下，初始变性：设为98℃3分钟；变性：设为98℃10秒；退火：设为60℃30秒；延伸：设为72℃2.5分钟为1个循环，进行30个循环；最终延伸：设为72℃7分钟。

然后，将含有扩增的CcpyrG基因的DNA片段(4463bp)的末端用T4多核苷酸激酶(东洋纺)磷酸化。在用SmaI消化pUC18后，用大肠杆菌碱性磷酸酶(东洋纺)脱磷酸化，并与含有磷酸化的CcpyrG基因的DNA片段连接。接着，用以下引物组对含有CcpyrG基因的上游和下游区域的pUC18侧进行PCR扩增，使含有CcpyrG基因的区域缺失。

CcPyrG-del_FW2：

5’-CACTCGATCTACCAAATCGACG-3’(SEQ ID NO:66)

CcPyrG-del_RV2：

5’-CCTATCCGGATATGCAGTCAC-3’(SEQ ID NO:67)

PCR使用Phusion Hot Start II高保真DNA聚合酶进行。温度条件如下，初始变性：设为98℃3分钟；变性：设为98℃10秒；退火：设为60℃30秒；延伸：设为72℃3分钟为1个循环，进行30个循环；最终延伸：设为72℃7分钟。

然后，将得到的PCR片段用T4多核苷酸激酶磷酸化后，进行自连接，构建目的CcpyrG基因破坏构建体(pUC-CcPyrG-del_C1)。

2)棒状弯孢菌(C.clavata)BAUA-2787株的CcpyrG基因破坏转化

将以pUC-CcPyrG-del_C1为模板，用CcPyrG-del_FW3/CcPyrG-del_RV3的引物组进行了PCR扩增获得的片段用于CcpyrG基因破坏。PCR使用Phusion Hot Start II高保真DNA聚合酶进行。温度条件如下，初始变性：设为98℃30秒；变性：设为98℃10秒；退火：设为63℃30秒；延伸：设为72℃30秒为1个循环，进行35个循环；最终延伸：设为72℃5分钟。

棒状弯孢菌(C.clavata)BAUA-2787株的转化基本按照[使用转录因子高表达株的分析]所说明的操作流程进行。其中，CM+1mg/ml 5-FOA+0.2％尿苷+0.02％尿嘧啶被用作筛选培养基。

3)TF068-005基因破坏构建体的构建(图13)

将用于破坏TF068-005基因的构建体的构建方案示于图13，所述TF068-005基因如上所述被证实编码转录因子。

如图13所示，首先，以棒状弯孢菌(C.clavata)BAUA-2787株的基因组为模板，使用与TF068-005基因的上游区域互补的引物TF068-005_L-arm_FW1和TF068-005_L-arm_RV1扩增左臂(1147bp)。同样，使用与TF068-005基因的下游区域互补的引物TF068-005_R-arm_FW1和TF068-005_R-arm_RV1扩增右臂(1205bp)。此外，使用引物CcPyrG-mark_FW1和CcPyrG-mark_RV1扩增选择标记基因pyrG(2231bp)。将扩增的各片段的电泳照片示于图14。

然后，按照In-Fusion HD克隆试剂盒(Clontech)的操作流程，依次将上述通过PCR扩增的左臂、pyrG标记和右臂插入到试剂盒附带的线性状pUC19质粒载体中。将得到的载体导入到大肠杆菌JM109株，从3个克隆的转化体制备质粒，进行测序。

用于扩增各DNA片段的引物序列如下所示：

TF068-005_L-arm_FW1：

5’-cggtacccggggatcCTCTGAAGCGGTCAAGGATAACG-3’(SEQ ID NO:68)

TF068-005_L-arm_RV1：

5’-atgaagcagagcggcGAGCCTAAGATATGCCAGGAGG-3’(SEQ ID NO:69)

TF068-005_R-arm_FW1：

5’-ctagcaaccgtcatgCCATAGACGTGGCACTCGAACG-3’(SEQ ID NO:70)

TF068-005_R-arm_RV1：

5’-cgactctagaggatcCGTCTTAAGGATGGTTCAGCTGC-3’(SEQ ID NO:71)

CcPyrG-mark_FW1：

5’-CATGACGGTTGCTAGGGTCG-3’(SEQ ID NO:72)

CcPyrG-mark_RV1：

5’-GCCGCTCTGCTTCATTGCTG-3’(SEQ ID NO:73)

(小写字母表示用于In-Fusion反应的15bp重叠序列)

4)用TF068-005基因破坏构建体的转化(图15)

图15中示意性地示出将上述2)中制作的棒状弯孢菌(C.clavata)BAUA-2787株的CcpyrG基因破坏株用TF068-005基因破坏构建体进行转化的方法。首先，通过限制酶EcoRI(日本宝生物株式会社)消化使TF068-005基因破坏构建体线性化，使用Ethachinimate(NIPPON GENE)进行纯化。接着，将线性化的构建体导入到棒状弯孢菌(C.clavata)BAUA-2787pyrG基因破坏株中，进行转化。转化基本按照[使用转录因子高表达株的分析]所说明的操作流程进行。其中，棒状弯孢菌(C.clavata)BAUA-2787pyrG基因破坏株的培养使用CM+5mM尿苷+5mM尿嘧啶培养基，转化体的筛选使用MM琼脂培养基[1％葡萄糖、0.6％NaNO₃、0.052％KCl、0.052％MgSO₄·7H2O、0.152％KH₂PO₄和赫特纳(Hutner)微量元素(pH6.5)]进行。

5)TF068-005基因破坏株的抗菌活性试验

将如上制作的TF068-005基因破坏株的分生孢子悬浮液接种到100ml的CM培养基，在26℃、130rpm培养72小时。用Miracloth滤布过滤培养液除去菌体，通过0.22μm过滤器灭菌后，使其渗入纸盘。将该纸盘和从每个琼脂培养基切下的灰霉病菌(Botrytis cinerea)的菌丝在PDA培养基上相隔约2.5cm放置，在26℃对峙培养3天。阳性对照为野生株棒状弯孢菌(C.clavata)BAUA-2787株的培养液，阴性对照为未培养菌体的CM培养基。

6)转录因子基因(TF068-005)破坏株的总RNA的制备

将TF068-005基因破坏株和野生株的分生孢子悬浮液接种到30ml的CM培养基，在26℃、130rpm振荡培养72小时。然后，用Miracloth滤布过滤培养液，回收菌体。称量0.8g菌体用液氮冷冻后，用研钵和研杵磨碎。将该菌体悬浮在10ml的ISOGEN(NIPPON GENE)中并静置10分钟，加入2ml氯仿并用涡旋混合器搅拌后，以4,700×g离心10分钟。回收水层，加入5ml异丙醇并用涡旋混合器搅拌后，以4,700×g离心10分钟。舍弃上清液，加入5ml的75％乙醇进行洗涤，以4,700×g离心10分钟后再次舍弃上清液，将RNA沉淀溶解在200μl无核酸酶水中。使用RNeasy Plant Mini Kit(QIAGEN)再次纯化得到的RNA溶液。

7)转录因子基因(TF068-005)破坏株的RNA-seq分析

使用Truseq RNA样品制备试剂盒v2(illumina)，从如上制备的总RNA制备RNA-Seq用文库，用于下一代测序仪(MiSeq)(双末端，读取长度75)。使用TopHat程序将得到的序列数据映射到棒状弯孢菌(C.clavata)的基因组序列。

8)转录因子基因破坏株和野生株中KK-1的提取和定量

将TF068-005基因破坏株和野生株的分生孢子悬浮液接种到30ml的CM培养基，在26℃、130rpm振荡培养10天。向培养液中加入15ml乙酸乙酯，振荡1小时后，以4,700×g离心15分钟。回收乙酸乙酯层，使其脱水以干燥并作为菌体外组分。然后，向回收乙酸乙酯层后的水层加入10ml丙酮，用涡旋混合器搅拌后，通过离心浓缩除去丙酮。向其中加入15ml乙酸乙酯，用涡旋混合器搅拌后，以4,700×g离心10分钟。将乙酸乙酯层回收并进行离心浓缩，将其作为菌体内组分。将得到的提取物再次溶解在乙酸乙酯中，然后用于LC/MS分析。

<LC>

仪器：ACQUITY UPLC I-Class系统(Waters)

色谱柱：Acquity UPLC BEH C18 2.1x100mm

流动相：DW+0.1％甲酸/乙腈+0.1％甲酸＝

50/50(0.5分钟)→2/98(3.4分钟)

梯度：50％-98％的乙腈+0.1％甲酸(0.5-3.4分钟)

流速：0.6ml/分钟

检测波长：273nm

<MS>

仪器：Xevo G2 QTof(Waters)

离子化条件：负离子

<结果与讨论>

本实施例中，得到5株其中确认到TF068-005基因的破坏和核的钝化的株，因此研究这些株在培养上清液中的抗菌活性。将上述抗菌活性试验的结果示于图16。图16中揭示了获得的5株TF068-005基因破坏株中的3株的抗菌活性试验结果。如图16所示，在阳性对照(野生株的培养液)中，观察到灰霉病菌向纸盘侧延伸的菌丝延伸受到抑制；而在TF068-005基因破坏株的培养液中，则未检测到抑制活性，从而得到与阴性对照(只有培养液)相同的结果。由此认为，在TF068-005基因破坏株中KK-1生产能力明显下降，这强烈表明TF068-005基因密切参与KK-1的生物合成

因此，关于TF068-005基因破坏株，进行了全面的基因表达分析(RNA-seq)和KK-1生产量的分析。在全面的基因表达分析(RNA-seq)中，将野生株作为比较对照，对TF068-005基因破坏株(2株)进行分析。将其结果示于图17。图17中，“del_TF”表示TF068-005基因破坏株的结果。此外，在图17所示的图表中，纵轴的“RPKM”为每百万映射的序列读段中每千碱基外显子的读段数(reads per kilobase of exon per million mapped sequence reads)，是将映射的序列(读段)数用整体的读段总数和转录物的序列长度进行归一化的值。

如图17所示，在TF068-005基因破坏株中，推定的生物合成簇所含有的基因的表达量与野生株相比明显更低，而该簇中未含有的周围的一组基因的表达量除了TRAF01000068000011基因以外，与野生株相同。予以说明，根据注释信息，TRAF01000068000011基因的功能被推定为参与在细胞溶质和核中合成的糖核苷酸向内质网和高尔基体的输送的核苷酸糖转运蛋白。由于KK-1的结构中不存在糖核苷酸，因此认为该基因与生物合成的关联性低。

另外，将通过LC/MS测定TF068-005基因破坏株(5株)中的KK-1生产量的结果示于图18。如图18所示，在TF068-005基因破坏株(5株)中的任一株中，均未在培养上清液和菌体内检测到KK-1。

由以上的TF068-005基因破坏株的相关结果，以及TF068-005基因高表达株中簇内基因表达量和KK-1生产量明显增高可知，推定的基因簇负责KK-1的生物合成，而且TF068-005基因调控组成KK-1生物合成基因簇的各基因的转录。

〔实施例3〕

本实施例中，对于实施例1中推定的KK-1生物合成基因簇中所含有的各基因，制作基因破坏株，分析各基因的功能。

1)各簇基因破坏构建体的构建(图19)

除了实施例2验证的TRAF01000068000005(转录因子基因)以外，关于KK-1生物合成基因簇中所含有的各基因，将上游侧约1,000bp的区域作为左臂，将下游侧约1,000bp的区域作为右臂，通过以棒状弯孢菌(C.clavata)BAUA-2787株的基因组DNA为模板的PCR来得到两个基因片段。此外，对用作转化体的筛选标记的pyrG基因进行PCR扩增。接着，使用In-Fusion Cloning Kit试剂盒(Clontech)，将在上述PCR中扩增的左臂、pyrG基因、右臂依次连接而成的基因片段插入到pUC19中，制作各基因破坏构建体(图19)。

在对构成各个构建体的各DNA片段进行PCR扩增时使用的引物序列和PCR条件如下所示。予以说明，用于进行In-Fusion反应的重叠的序列(15bp)用小写字母表示。

·pyrG筛选标记扩增用(实施例2使用的引物)

CcPyrG-mark_FW1：

5’-CATGACGGTTGCTAGGGTCG-3’(SEQ ID NO:72)

CcPyrG-mark_RV1：

5’-GCCGCTCTGCTTCATTGCTG-3’(SEQ ID NO:73)

·TRAF01000135000002破坏构建体左臂(982bp)扩增用

TRAF135-002_del_L-arm_FW：

5’-cggtacccggggatcGACCCATTGCAGCTTGTG-3’(SEQ ID NO:74)

TRAF135-002_del_L-arm_RV：

5’-atgaagcagagcggcGTGCAGTATGGTGTCTAAAACG-3’(SEQ ID NO:75)

·TRAF01000135000002破坏构建体右臂(950bp)扩增用

TRAF135-002_del_R-arm_FW：

5’-ctagcaaccgtcatgGATGAATGAGCACCCTGTTAG-3’(SEQ ID NO:76)

TRAF135-002_del_R-arm_RV：

5’-cgactctagaggatcGTACATTACAAAAACCTGTTGCAG-3’(SEQ ID NO:77)

·TRAF01000135000001破坏构建体左臂(1,000bp)扩增用

TRAF135-001_del_L-arm_FW：

5’-cggtacccggggatcGTCCCACGTGCAGCTTCAAC-3’(SEQ ID NO:78)

TRAF135-001_del_L-arm_RV：

5’-atgaagcagagcggcCGTGGAGTATCCCAGGATGG-3’(SEQ ID NO:79)·TRAF01000135000001破坏构建体右臂(982bp)扩增用

TRAF135-001_del_R-arm_FW：

5’-ctagcaaccgtcatgCCAGCCAAAGGGTATCATGG-3’(SEQ ID NO:80)

TRAF135-001_del_R-arm_RV：

5’-cgactctagaggatcTGAGGGCAGCGTAGCCTG-3’(SEQ ID NO:81)

·TRAF01000068000002破坏构建体左臂(992bp)扩增用

TRAF068-002_del_L-arm_FW：

5’-cggtacccggggatcGTGGATAAATTCGTACCCTTTG-3’(SEQ ID NO:82)

TRAF068-002_del_L-arm_RV：

5’-atgaagcagagcggcCTGATCTTTGTTGTGGTCGTG-3’(SEQ ID NO:83)

·TRAF01000068000002破坏构建体右臂(1,014bp)扩增用

TRAF068-002_del_R-arm_FW：

5’-ctagcaaccgtcatgCAGTTTGGCACTTGAGCATC-3’(SEQ ID NO:84)

TRAF068-002_del_R-arm_RV：

5’-cgactctagaggatcCACGGAAAGGAACTCCTACAG-3’(SEQ ID NO:85)

·TRAF01000068000003破坏构建体左臂(912bp)扩增用

TRAF068-003_del_L-arm_FW：

5’-cggtacccggggatcCTCTGGGAAAAGCGGTTAG-3’(SEQ ID NO:86)

TRAF068-003_del_L-arm_RV：

5’-atgaagcagagcggcGAAGAACCGAGAGCGAGAG-3’(SEQ ID NO:87)·TRAF01000068000003破坏构建体右臂(995bp)扩增用

TRAF068-003_del_R-arm_FW：

5’-ctagcaaccgtcatgCTTGCATCTACCTAGATATTTCACG-3’(SEQ ID NO:88)

TRAF068-003_del_R-arm_RV：

5’-cgactctagaggatcCAGAGAATCAGCAGAGACACC-3’(SEQ ID NO:89)

·TRAF01000068000004破坏构建体左臂(991bp)扩增用

TRAF068-004_del_L-arm_FW：

5’-cggtacccggggatcCCCTGGTAGTTCAGTGGAAGTAAG-3’(SEQ ID NO:90)

TRAF068-004_del_L-arm_RV：

5’-atgaagcagagcggcTGATAGAGGTACGGGGGTG-3’(SEQ ID NO:91)·TRAF01000068000004破坏构建体右臂(1,003bp)扩增用

TRAF068-004_del_R-arm_FW：

5’-ctagcaaccgtcatgTGCTTGGCTGCTTCAAATC-3’(SEQ ID NO:92)

TRAF068-004_del_R-arm_RV：

5’-CGACTCTAGAGGATCCTAATACTTGTCGTCCCACTGATG-3’

(SEQ ID NO:93)

·TRAF01000068000006破坏构建体左臂(993bp)扩增用

TRAF068-006_del_L-arm_FW：

5’-cggtacccggggatcGCAGTACATCGTCAGGGTC-3’(SEQ ID NO:94)

TRAF068-006_del_L-arm_RV：

5’-atgaagcagagcggcGATGAATAAGGCGAAGGAAAG-3’(SEQ ID NO:95)

·TRAF01000068000006破坏构建体右臂(579bp)扩增用

TRAF068-006_del_R-arm_FW：

5’-ctagcaaccgtcatgCCCTCTTTTTTCTTGCTGTCTC-3’(SEQ ID NO:96)

TRAF068-006_del_R-arm_RV：

5’-cgactctagaggatcGAAGGAAGGACGGATACTGG-3’(SEQ ID NO:97)·TRAF01000068000007破坏构建体左臂(769bp)扩增用

TRAF068-007_del_L-arm_FW：

5’-cggtacccggggatcGATGAGCGTAGAATTCGTAAAAAG-3’(SEQ ID NO:98)

TRAF068-007_del_L-arm_RV：

5’-atgaagcagagcggcGCGAACGGGCGTTTTTC-3’(SEQ ID NO:99)

·TRAF01000068000007破坏构建体右臂(579bp)扩增用

TRAF068-007_del_R-arm_FW：

5’-ctagcaaccgtcatgGAAGGAAGGACGGATACTGG-3’(SEQ ID NO:100)

TRAF068-007_del_R-arm_RV：

5’-cgactctagaggatcCCCTCTTTTTTCTTGCTGTCTC-3’(SEQ ID NO:101)

·TRAF01000068000008破坏构建体左臂(716bp)扩增用

TRAF068-008_del_L-arm_FW：

5’-cggtacccggggatcCTCCTTATTTTGCAACTTCTGATAC-3’(SEQ ID NO:102)

TRAF068-008_del_L-arm_RV：

5’-atgaagcagagcggcCGTGTTGATTTTGGTAATTTTG-3’(SEQ ID NO:103)

·TRAF01000068000008破坏构建体右臂(769bp)扩增用

TRAF068-008_del_R-arm_FW：

5’-ctagcaaccgtcatgGATGAGCGTAGAATTCGTAAAAAG-3’(SEQ ID NO:104)

TRAF068-008_del_R-arm_RV：

5’-cgactctagaggatcGCGAACGGGCGTTTTTC-3’(SEQ ID NO:105)

·TRAF01000068000009破坏构建体左臂(716bp)扩增用

TRAF068-009_del_L-arm_FW：

5’-cggtacccggggatcCGTGTTGATTTTGGTAATTTTG-3’(SEQ ID NO:106)

TRAF068-009_del_L-arm_RV：

5’-atgaagcagagcggcCTCCTTATTTTGCAACTTCTGATAC-3’(SEQ ID NO:107)

·TRAF01000068000009破坏构建体右臂(989bp)扩增用

TRAF068-009_del_R-arm_FW：

5’-ctagcaaccgtcatgCTAGCAGCCATAAGAGACGTAACC-3’(SEQ ID NO:108)

TRAF068-009_del_R-arm_RV：

5’-cgactctagaggatcGTTTTCATTGCATGCTCCG-3’(SEQ ID NO:109)·PCR反应条件

PCR使用Phusion高保真DNA聚合酶(赛默飞世尔科技)进行。温度条件如下，初始变性：设为98℃30秒；变性：设为98℃10秒；退火：设为60℃30秒；延伸：设为72℃45秒为1个循环，进行30个循环；最终延伸：设为72℃进行5分钟。

2)棒状弯孢菌(C.clavata)pyrG破坏株的转化

图20的A中示意性地示出将实施例2的2)中制作的棒状弯孢菌(C.clavata)BAUA-2787株的CcpyrG基因破坏株用各基因破坏构建体转化的方法。通过规定的限制酶(如图20的B所示)使构建的各基因破坏构建体线性化。接着，按照实施例2的[使用转录因子高表达株的分析]所说明的操作步骤，将线性化的构建体导入到棒状弯孢菌(C.clavata)BAUA-2787pyrG基因破坏株。在培养宿主的棒状弯孢菌(C.clavata)BAUA-2787pyrG基因破坏株时，使用加入了5mM尿苷和尿嘧啶的液体CM培养基，且转化体的筛选在MM琼脂培养基中进行。

3)簇基因破坏株的培养

将上述2)中得到的各基因破坏株的分生孢子悬浮液接种到30ml的KM培养基(带挡板的100ml厄伦美厄烧瓶)中，在26℃、130rpm振荡培养3天，作为预培养液。接着，将300μl预培养液接种到30ml的CM培养基(带挡板的100ml厄伦美厄烧瓶)中，在26℃、130rpm振荡培养7天。

4)培养体系内的代谢物的提取和分析

在上述3)中得到的培养液中加入15ml乙酸乙酯，以130rpm振荡1小时后，以4,200×g离心15分钟。回收乙酸乙酯层，将离心浓缩的层作为菌体外组分。然后，向回收乙酸乙酯层后的水层加入10ml丙酮，用涡旋混合器搅拌后，通过离心浓缩除去丙酮。向其中加入15ml乙酸乙酯，用涡旋混合器搅拌后，以4,200×g离心10分钟。将乙酸乙酯层回收并进行离心浓缩，将其作为菌体内组分。将得到的提取物与菌体内外的组分一起溶解在500μl乙酸乙酯中，然后将1μl用于LC/MS分析。

·LC/MS分析条件

<LC>

仪器：ACQUITY UPLC I-Class系统(Waters)

色谱柱：Acquity UPLC BEH C18 2.1x100mm

流动相：DW/MeCN＝50/50(0.5分钟)→2/98(3.4分钟)(含有各溶剂0.1％甲酸)

流速：0.6ml/分钟

检测波长：273nm

<MS>

仪器：Xevo G2 QTof(Waters)

离子化条件：负离子

<结果与讨论>

对于本实施例制作的各基因破坏株和实施例2制作的转录因子基因破坏株，研究了KK-1的生产率。将其结果示于图21。图21中，各株的KK-1生产量(相对于野生株的相对量)用平均±标准偏差(n＝2)表示。如图21所示，将生物合成环状肽的基本骨架的NRPS(TRAF01000135000001)基因破坏的株中，KK-1的产生完全消失，表明该基因是KK-1的生物合成所必需的。

另外，如图21所示，基因簇中所含有的一组基因中的5种基因(TRAF01000135000002、TRAF01000068000002、TRAF01000068000003、TRAF01000068000007和TRAF01000068000008)破坏株的KK-1生产量与野生株相比大幅降低。由此认为，这些基因在对通过NRPS生物合成的环状肽骨架进行修饰等阶段密切参与KK-1的产生。

另外，如图21所示，关于3种基因(TRAF01000068000004、TRAF01000068000006和TRAF01000068000009)破坏株，虽然与野生株相比的变动幅度小于上述5个基因，但KK-1的生产量下降。由此表明这3种基因也参与KK-1的产生。推定出TRAF01000068000006所编码的蛋白质实际上是ABC转运体，认为它参与菌体内产生的KK-1向细胞外的排出。此外，关于注释为α/β水解酶的TRAF01000068000009，在由放线菌即娄彻氏链霉菌(Streptomycesrochei)7434AN4株产生的聚酮类抗生素兰卡霉素生物合成簇内，含有编码使误摄取的底物水解的硫酯酶的基因，因此认为该基因也可能具有同样的作用。予以说明，TRAF01000068000004的大小较小，为8.1kDa，且也不存在相似的蛋白质，因此也认为其可能不具有特定功能。

〔实施例4〕

本实施例中，将在实施例1～3中进行了功能分析的KK-1生物合成基因簇导入到米曲霉，探究米曲霉中KK-1的异种产生。

1)米曲霉的菌体、培养基(A.oryzae strain and growth media)

在米曲霉(A.oryzae)中，作为导入KK-1生物合成基因簇的亲本菌株，使用NS4ΔadeA株(sC-、niaD-、ΔligD::sC、ΔadeA::ptrA)。普通的生长和分生孢子的形成使用满足菌株营养需求性的Czapek-dox(CD)最小培养基[0.6％NaNO₃、0.052％KCl、0.152％KH₂PO₄、0.0001％FeSO₄·7H₂O、0.00088％ZnSO₄·7H₂O、0.00004％CuSO₄·5H₂O、0.000015％MnSO₄·4H₂O、0.00001％Na₂B₄O₇·10H₂O、0.000005％(NH₄)₆Mo₇O₂₄·4H₂O、0.059％MgSO₄·7H₂O和2％葡萄糖]进行。即，使用加入70mM谷氨酸钠代替NaNO₃作为氮源的培养基(CDE)，或者在CDE中加入0.01％腺嘌呤而形成的培养基(CDEA)。在用米曲霉amyB启动子诱导导入的基因表达时，使用YPM培养基(1％酵母提取物、2％多聚蛋白胨、2％麦芽糖)，在评价KK-1的生产率时也同样使用YPM培养基。

2)NRPS基因分割导入载体的构建(图22)

图22中示意性地示出在导入KK-1生物合成基因簇时使用的载体的构建方案。如图22所示，在KK-1生物合成基因簇中所含有的基因中，将NRPS基因分割成2部分导入到米曲霉中。即，将全长39kb的基因分成前半部分(约20kb)和后半部分(约20kb)，分别亚克隆到载体质粒中，导入到米曲霉中。然后，筛选米曲霉内两个片段彼此连接的转化体。作为载体质粒，使用其标记可通过内源性Cre重组酶表达进行再利用的pAAG-Cre。

首先，为了扩增前半部分的基因，使用引物NRPS-fh-F和NRPS-fh-R进行PCR。作为PCR的模板，使用棒状弯孢菌(C.clavata)BAUA-2787株的基因组DNA。PCR中使用的酶为PrimeSTAR GXL DNA聚合酶(日本宝生物株式会社)，按照产品说明书进行PCR。得到的PCR产物暂时连接到pZErO-2(Invitrogen)的EcoRV切割位点。通过NotI切割将NRPS基因前半部分从得到的质粒中切出，并连接到pAAG-Cre的相同位点。筛选其中米曲霉用启动子PamyB和NRPS基因在正确方向上连接的质粒，作为NRPS基因前半部分导入载体pAAG-Cre/KK1-F。

NRPS基因后半部分的基因扩增难以通过一次PCR扩增来进行克隆，因此将其再分割成3部分进行扩增，通过In-Fusion克隆法进行连接。首先，通过PCR扩增后半部分的片段A、B、C。后半部分的片段A的扩增使用引物NRPS-rh-IF-Fa和NRPS-rh-IF-Ra，后半部分的片段B的扩增使用NRPS-rh-IF-Fb和NRPS-rh-IF-Rb，后半部分的片段C的扩增使用NRPS-rh-IF-Fc和NRPS-rh-IF-Rc。通过In-Fusion克隆法将各个片段和经NotI消化的pAAG-Cre连接，并将正确连接的质粒作为NRPS基因后半部分导入载体pAAG-Cre/NRPSrh。

In-Fusion克隆使用In-Fusion HD克隆试剂盒(Clontech)，按照附带的产品说明书记载的方法进行。确认NRPS基因前半部分导入载体、后半部分导入载体和基因序列，确认NRPS中未发生突变。

使用的引物序列如下所示：

NRPS-fh-F：

TCGACAAGCTTGCGGCCGCCACGTGACTAGTATGGCCAGCGACATCAATACTCATCCAG(SEQ IDNO:110)

NRPS-fh-R：

ACTAGTCACGTGGCGGCCGCGGCGCGCCAAGATCGTCTTGCTGTACG(SEQ ID NO:111)

NRPS-rh-IF-Fa：

GATGCGCTAGCGGCCGCGAAGTGGTCCTTGTCGCTGGTGAC(SEQ ID NO:112)

NRPS-rh-IF-Ra：

TGCCGTTCGCATTCATAGGCATCTCGTC(SEQ ID NO:113)

NRPS-rh-IF-Fb：

TGAATGCGAACGGCAAGGTTGACAG(SEQ ID NO:114)

NRPS-rh-IF-Rb：

CTTGGTTGCTGGCTTCGTCGTTGTC(SEQ ID NO:115)

NRPS-rh-IF-Fc：

AAGCCAGCAACCAAGTCGAAGATTG(SEQ ID NO:116)

NRPS-rh-IF-Rc：

GTCACTAGTGCGGCCGCCTATTTTTGCAAGATCTTGTTCAAAC(SEQ ID NO:117)

3)簇基因导入载体的构建(图22)

如实施例2所述，表明在KK-1生物合成基因簇中所含有的基因中，TRAF01000068000004不是KK-1的生物合成所必需的。此外，由于TRAF01000068000005是调控簇基因表达的转录因子，因此预想在通过米曲霉用启动子调控全部基因时，并不需要TRAF01000068000005。为了将除了上述NRPS基因和这两种基因以外的7个基因导入到米曲霉中，如图22所示，构建了装载这些基因的基因导入载体。

作为装载基因的质粒，选择能够同时最大装载3个基因，且能够用amyB启动子调控全部基因的pA3AXPC(可由日本东北大学基因信息系统学领域五味胜也教授提供)。该质粒还装载有利用Cre重组酶和loxP序列的Cre-loxP标记再利用系统，并且是适合于在多阶段的基因导入的载体。

首先，以棒状弯孢菌(C.clavata)BAUA-2787株的cDNA为模板进行PCR，扩增各基因。TRAF01000068000002基因的扩增使用引物TR02-SpeI-F和TR02-SpeI-R的组合，TRAF01000068000003基因的扩增使用引物TR03-NotI-F和TR03-NotI-R的组合。将得到的扩增片段暂时连接到pZErO-2的EcoRV切割位点(分别命名为pZTR02和pZTR03)。然后，通过SpeI消化从pZTR02切出TRAF01000068000002基因，通过NotI消化从pZTR03切出TRAF01000068000003基因。切出的基因按照TRAF01000068000002(SpeI)和TRAF01000068000003(NotI)的顺序，导入到pA3AXPC的SpeI、NotI位点。筛选其中两个基因插入方向正确的质粒，作为pATR0203。

接着，TRAF01000068000006基因的扩增使用引物TR06-NheI-F和TR06-NheI-R的组合，TRAF01000068000007基因的扩增使用引物TR07-NotI-F和TR07-NotI-R的组合，TRAF01000068000009基因的扩增使用引物TR08-SpeI-F和TR08-SpeI-R的组合。将得到的PCR产物暂时连接到pZErO-2的EcoRV切割位点(分别命名为pZTR06、pZTR07和pZTR08)。然后，通过NheI消化从pZTR06切出TRAF01000068000006基因，通过NotI消化从pZTR07切出TRAF01000068000007基因，通过SpeI消化从pZTR08切出TRAF01000068000008基因。将切出的基因按照TRAF01000068000006(NheI)、TRAF01000068000008(SpeI)和TRAF01000068000007(NotI)的顺序，分别导入到pA3AXPC的NheI、SpeI和NotI位点。筛选其中全部基因插入方向正确的质粒，作为pATR678。

最后，TRAF01000068000009基因的扩增使用引物TR09-NheI-F和TR09-NheI-R的组合；对于TRAF01000135000002基因，则使用引物OMT-NotI-F和OMT-NotI-R的组合。将得到的PCR产物暂时连接到pZErO-2的EcoRV切割位点(分别命名为pZTR09和pZOMT)。然后，通过NheI消化从pZTR09切出TRAF01000068000009基因，通过NotI消化从pZOMT切出TRAF01000135000001基因。将切出的基因按照TRAF01000068000009(NheI)和TRAF01000135000001OMT(NotI)的顺序，导入到pA3AXPC的NheI、NotI位点。筛选其中两个基因插入方向正确的质粒，作为pATR09OMT。

使用的引物序列如下所示：

TR02-SpeI-F：

GGACTAGTATGACTGAACCCACATGGAAG(SEQ ID NO:118)

TR02-SpeI-R：

GGACTAGTTTAATAATCTACTTCAAGCAC(SEQ ID NO:119)

TR03-NotI-F：

ATAAGAATGCGGCCGCATGGCGTTGCAAGAGCG(SEQ ID NO:120)

TR03-NotI-R：

ATAAGAATGCGGCCGCTCAAGATGGGAAAGCCGCTG(SEQ ID NO:121)

TR06-NheI-F：

CTAGCTAGCATGAGTGCTATCGAGCTGC(SEQ ID NO:122)

TR06-NheI-R：

CTAGCTAGCTCAGCGATTGAGGGCCTGG(SEQ ID NO:123)

TR07-NotI-F：

ATAAGAATGCGGCCGCATGAAGCTCACCGTTTTCAG(SEQ ID NO:124)

TR07-NotI-R：

ATAAGAATGCGGCCGCTCAGAGCCGCGCCAAC(SEQ ID NO:125)

TR08-SpeI-F：

GGACTAGTATGACGAAAAGGGAAAGCAAC(SEQ ID NO:126)

TR08-SpeI-R：

GGACTAGTCTACGCGTTTTCTTTCGAC(SEQ ID NO:127)

TR09-NheI-F：

CTAGCTAGCATGGAGAGCGAAGACAATCC(SEQ ID NO:128)

TR09-NheI-R：

CTAGCTAGCTCAGCAGTATCCCATCGG(SEQ ID NO:129)

OMT-NotI-F：

ATTTGCGGCCGCATGGACCCGAGACAGTCACGGATC(SEQ ID NO:130)

OMT-NotI-R：

ATTTGCGGCCGCTTATGGTGTGGTGGGTTGCCATTC(SEQ ID NO:131)

4)向米曲霉中导入基因的方法

使用上述3)制作的各种质粒转化米曲霉，使用原生质体PEG法进行。将1×10⁷个亲本菌株(NS4ΔadeA株)的分生孢子接种到200ml容量厄伦美厄烧瓶中100ml的YPD液体培养基(1％酵母提取物、2％多聚蛋白胨和2％葡萄糖)中，将在30℃以20小时、160转振荡培养的菌丝用Miracloth滤布(CALIBIOCHEM公司)过滤，收集菌体。用无菌水洗涤，用干热灭菌的刮匙按压菌体进行脱水。将收集的菌丝放入50ml容量试管，加入用0.20μm过滤器过滤的用于原生质体形成的溶液[0.8M NaCl和10mM磷酸缓冲液(pH 6.0)中含10mg/ml溶壁酶(Sigma公司)、5mg/ml纤维素酶Onozuka(Yakult药品工业株式会社)、2.5mg/ml Yatalase(日本宝生物株式会社)]并进行悬浮。在30℃、83rpm下振荡3小时，消化细胞壁，由此制作原生质体。反应后，用灭菌的Miracloth滤布将未消化的菌体过滤，在4℃、2,500×g下将滤液离心分离5分钟，回收原生质体。将回收的原生质体用10ml的0.8M NaCl洗涤，在4℃、2,500×g下再次离心分离5分钟，由此使原生质体沉淀并回收。加入溶液I[0.8M NaCl、10mM CaCl₂、10mMTris-HCl(pH8.0)]以使原生质体变为2×10⁸个/ml，悬浮后，加入1/5量的溶液II[40％(w/v)PEG4000、50mM CaCl₂、50mM Tris-HCl(pH 8.0)]，充分混合。将240μl原生质体溶液分注到15ml容量试管中，加入5～20μg量的DNA溶液并充分混合，在冰中放置30分钟。接着，加入1ml的溶液II，充分混合后，在室温放置20分钟。加入10ml的溶液I，充分混合后在室温、2,500×g下离心5分钟，去除上清液，加入300μl的溶液I。将原生质体均匀地悬浮，将其散播到含有0.8M NaCl的CDE选择琼脂培养基中，然后从周围注入5ml事先加温到55℃的同样成分的软琼脂培养基[0.6％(w/v)Agar]，重叠成多层以使原生质体迅速地均匀悬浮。然后，在30℃进行培养，直至形成菌落。

5)米曲霉中的标记再利用

米曲霉中的标记再利用按照以下方法进行。即，该方法如下：在突变型loxP序列(lox66和lox71)之间配置adeA选择标记和Cre重组酶，使Cre重组酶表达，由此在loxP序列间引发环出，从而除去adeA选择标记。本文中，Cre重组酶能够通过Xylose诱导型启动子诱导表达。即，将整合了上述系统的菌株接种到以Xylose为碳源的培养基中，由此能够使Cre重组酶表达，从而获得去除adeA选择标记的菌株。去除adeA选择标记的菌株会恢复腺嘌呤需求性，因此能够再次使用adeA选择标记筛选基因重组体。

6)米曲霉内的KK-1NRPS基因重构(图23)

将利用Cre-loxP系统分2个阶段将NRPS基因的前半部分和后半部分导入的方案示意性地示于图23。如图23所示，在将载体导入到米曲霉中时，首先将装载NRPS基因前半部分的pAAG-Cre/NRPSfh导入。关于得到的转化体，通过PCR确认载体的导入。为了将后半部分导入到该株，通过Cre-loxP系统进行标记再利用。为了使载体内的Cre重组酶表达(用xynG2启动子进行调控)，使菌体在含有Xylose且添加有腺嘌呤的CDE培养基(即CDEAX培养基)中生长。针对生长的菌体，筛选出标记adeA基因缺失的特征为呈现红色的菌落。对这些株进行核钝化，确认到菌株在未添加腺嘌呤的培养基中不能生长。

接着，为了将NRPS后半部分导入得到的标记再利用株，进行导入pAAG-Cre/NRPSrh的转化操作。针对得到的营养需求恢复株，通过PCR筛选其中前半-后半部分连接的株。最后从候选的菌株中提取DNA，通过PCR确认全长是否连接。结果是可确认NRPS基因全长的导入。

接着，通过连接部分的序列确认连接部分是否通过同源重组正确地重组。结果是未确认到连接部分存在突变和错位等。这些结果表明，在米曲霉内正确地重构了NRPS基因。

然后，为了将簇内其他基因导入到该株，通过Cre-loxP系统进行标记再利用。确认腺嘌呤需求性的恢复之后，将核纯化的株作为以后实施的全部基因导入的亲本菌株。

7)簇内必需基因在米曲霉内的高表达

对上述3)制作的、装载有簇基因的质粒pATR0203、pATR678和pATR09OMT依次反复进行标记再利用并导入到米曲霉中。但是，在导入了全部质粒的株中，确认到TRAF01000068000009基因的丢失。此外，对于该系统菌株，NRPS基因也可知发生了部分丢失。另外，对其他的系统菌株考察了是否存在基因丢失，结果多次观察到基因的丢失。根据这些结果认为，在标记再利用或转化操作时在接近的启动子序列之间有可能发生了环出。因此重新制定导入策略，如图24所示，为了尽量减少标记再利用或转化操作的数量，决定同时导入装载有7个基因的3种载体。结果是得到其中可确认到全部基因导入的株。

8)转录分析(图25)

接着，对于如上制作的导入了KK-1生物合成簇基因的转化的米曲霉，进行导入基因的表达分析。在YPM培养基(含有2％麦芽糖作为启动子诱导底物)中将菌株振荡培养24小时后，用Miracloth滤布过滤培养液，回收菌体。用液氮瞬间冷冻菌体，迅速在液氮下用研钵和研杵磨碎。将磨碎的菌体转移到1.5ml容量微量离心管中，按照RNeasy Plant Mini Kit(QIAGEN)的操作步骤提取RNA。为了避免DNA的混入，也按照附带的操作步骤进行柱上DNA酶处理。最后用50μl无RNA酶水洗脱2次，由此获得总RNA。

接着，从获得的总RNA合成cDNA。cDNA的合成使用高容量cDNA逆转录试剂盒(Applied Biosystem)，按照附带的操作步骤方法进行。将相当于4μg的获得的总RNA的量用于40μl的反应体系，从mRNA合成cDNA。逆转录的反应条件是在25℃孵育10分钟后，在37℃反应120分钟的条件，通过85℃、5秒的加热来使反应停止。得到的cDNA在使用之前保存在-20℃。

定量实时PCR(qRT-PCR)使用THUNDERBIRD SYBR qRCR Mix(东洋纺)，按照附带的说明书在20μl的体系中反应。该混合溶液中含有相当于400ng量的通过逆转录反应合成的cDNA。每份样品测定3次。PCR使用Mini Opticon实时PCR分析系统(BioRad)，分析软件使用BioRad CFX Manager 2.1。相对表达强度的计算是作为相同条件下测定的各基因相对于内部标准基因(组蛋白H2B)的表达量的表达量比。

使用的引物组如下所示：

·TRAF01000135000001基因用

NRPS-RT1-F：GACGCCACGAACGCATAGAC(SEQ ID NO:132)

NRPS-RT1-R：TTCCCAGAGAGGTAGATCGAC(SEQ ID NO:133)

·TRAF01000135000001基因用

NRPS-RT2-F：GACCGTTACAGCGAGTTCAG(SEQ ID NO:134)

NRPS-RT2-R：CTGAATTCCTCGCACAGAAC(SEQ ID NO:135)

·TRAF01000135000001基因用

NRPS-RT3-F：GAAGTTGAGAACGCCATGCT(SEQ ID NO:136)

NRPS-RT3-R：GATGCGAGATGGGAGCATGT(SEQ ID NO:137)

·TRAF01000068000002基因用

TR02-RT-F：GCCCTACTAGATCTGACCAC(SEQ ID NO:138)

TR02-RT-R：GCTGTTACCTTTTCCTCCTC(SEQ ID NO:139)

·TRAF01000068000003基因用

TR03-RT-F：AGATCTTAGACGAGCTGCTC(SEQ ID NO:140)

TR03-RT-R：AAACAGTCGCGAAGCGACTG(SEQ ID NO:141)

·TRAF01000068000006基因用

TR06-RT-F：ACGTCCAGGAAGCTATCGAG(SEQ ID NO:142)

TR06-RT-R：ATTGAGGGCCTGGGCTTGAC(SEQ ID NO:143)

·TRAF01000068000007基因用

TR07-RT-F：GTGATGAAGGCGCTGAAGAG(SEQ ID NO:144)

TR07-RT-R：CTCCGCAATTTCCGTGAGTG(SEQ ID NO:145)

·TRAF01000068000008基因用

TR08-RT-F：TGACTCTATGGTGGATGGTG(SEQ ID NO:146)

TR08-RT-R：CCTTGTTCAAGTGCCAGTAG(SEQ ID NO:147)

·TRAF01000068000009基因用

TR09-RT-F：GATTCCGTCACGAGACACTG(SEQ ID NO:148)

TR09-RT-R：AGTATCCCATCGGGCAACAG(SEQ ID NO:149)

·TRAF01000135000002基因用

OMT-RT-F：ACGTTCAAGACCTTCCAG(SEQ ID NO:150)

OMT-RT-R：GTTCCGGATGATTTGCAG(SEQ ID NO:151)

将定量实时PCR的结果示于图25。予以说明，图25中，O-MT是指TRAF01000135000002基因，NRPS-1～NRPS-3是指TRAF01000135000001基因(实施例1的NRPS基因)，TR02是指TRAF01000068000002基因，TR03是指TRAF01000068000003基因，TR06是指TRAF01000068000006基因，TR07是指TRAF01000068000007基因，TR08是指TRAF01000068000008基因，TR09是指TRAF01000068000009基因。如图25所示，表明了导入的全部基因表现出与组蛋白相同程度的表达水平，在导入了簇基因的米曲霉中，KK-1生物合成所必需的全部基因进行了高表达。

9)KK-1生产率评价

另外，针对如上制作的导入了KK-1生物合成簇基因的转化的米曲霉，评价了KK-1的生产率。

本实施例制作的转化的米曲霉被设计成导入的全部基因能够用PamyB启动子进行调控，因此在将麦芽糖作为碳源时能够诱导全部基因的表达。首先，将本实施例制作的转化的米曲霉的分生孢子悬浮液接种到100ml的YPM(麦芽糖2％)或CM(麦芽糖2％)中，在26℃、140rpm下振荡培养5天。接着，用丙酮和乙酸乙酯提取培养的菌体和培养液，进行浓缩干燥。将其溶解于乙腈，供LC/MS分析使用。LC/MS分析的条件按照在弯孢属(Curvularia sp.)中评价KK-1产生的条件。此外，上述提取物的抗菌性通过对作为抗菌性评价对象的灰霉病菌的生长抑制效果来评价。首先，使提取物渗入纸盘(薄，φ6mm)，将该纸盘和从每个琼脂培养基切下的灰霉病菌(Botrytis cinerea)的菌丝放置在CM培养基上，进行对峙培养。接着，根据灰霉病菌向纸盘周围的菌落延伸程度来评价抗菌活性。

将结果示于图26。图26的A表示LC/MS分析结果，B表示抗菌活性试验结果。如图26的A所示，在本实施例制作的来源于转化的米曲霉的提取物中，检测到与KK-1标准品的保持时间和分子量完全一致的峰。而且，如图26的B所示，在该提取物中观察到灰霉病菌的菌丝延伸抑制活性。从这些结果能够证实，本实施例制作的转化的米曲霉是以发挥在棒状弯孢菌(C.clavata)中鉴定的KK-1生物合成基因簇功能的形式导入的，能够异种产生KK-1。

本说明书中引用的所有出版物、专利和专利申请均通过直接引用而并入本说明书中。

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<110> 国立研究开发法人产业技术综合研究所

国立大学法人东北大学

组合化学工业株式会社

<120> 环状肽化合物合成相关基因、使用该基因的环状肽化合物制造方法以及具有该基因的转化体

<130> PH-7165-PCT

<150> JP 2017-000770

<151> 2017-01-05

<160> 151

<170> PatentIn version 3.5

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Leu His Gln Arg Lys Leu Pro Ala Glu Ser Leu Val Ala Val Leu Ala

20 25 30

Pro Arg Ser Cys Glu Thr Ile Ile Thr Phe Phe Gly Ile Leu Lys Ala

35 40 45

Asn Leu Ala Tyr Leu Pro Leu Asp Ile Asn Val Pro Ala Ala Arg Ile

50 55 60

Gln Ala Ile Leu Ser Ser Val Ala Gly Lys Lys Ile Leu Leu Leu Gly

65 70 75 80

Ser Asp Gln Ala Gln Pro Glu Ile Arg Leu Asp Asp Val Glu Phe Val

85 90 95

Gln Ile Asn Glu Thr Ile Asp His Asn Met Ala Lys Asp Asn Thr Thr

100 105 110

Arg Ser Gly Pro Leu Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser

115 120 125

Gly Ser Thr Gly Gln Pro Lys Gly Val Lys Val Glu His Arg Gly Ile

130 135 140

Val Arg Leu Val Lys Asn Ser Asn Val Val Ala Lys Met Pro Glu Ala

145 150 155 160

Ala Cys Val Ala His Leu Ser Asn Leu Ala Phe Asp Ala Ala Thr Trp

165 170 175

Glu Ile Tyr Ala Ala Leu Leu Asn Gly Gly Ser Leu Ile Cys Ile Asp

180 185 190

Tyr Phe Thr Thr Leu Asp Ser Lys Val Leu Glu Ala Val Phe Glu Arg

195 200 205

Glu Gln Ile Arg Ala Ala Met Phe Pro Pro Ala Leu Leu Lys Gln Cys

210 215 220

Leu Leu Asn Ile Pro Thr Thr Ile Ser Ala Leu Asp Val Ile Leu Ala

225 230 235 240

Ala Gly Asp Arg Phe Asp Arg Arg Asp Ala Ile Ala Ala Gln Ala Leu

245 250 255

Val Gly Gly Gly Val Tyr Asn Ala Tyr Gly Pro Thr Glu Asn Thr Thr

260 265 270

Leu Ser Thr Ile Tyr Asn Val Val Asp Gly Asp Thr Asn Val Asn Gly

275 280 285

Ile Pro Ile Gly Leu Pro Val Ser Asn Ser Gly Val Tyr Val Met Asp

290 295 300

Pro Asn Gln Gln Leu Val Pro Leu Gly Val Met Gly Glu Leu Val Val

305 310 315 320

Val Gly Asp Gly Val Ala Arg Gly Tyr Thr Asp Pro Ala Leu Asp Val

325 330 335

Asp Arg Phe Ile Lys Val Glu Ile Asp Gly Gln Ile Val Arg Ala Tyr

340 345 350

Arg Thr Gly Asp Arg Val Arg His Arg Pro Lys Asp Gly Gln Ile Glu

355 360 365

Phe Phe Gly Arg Met Asp Gln Gln Val Lys Ile Arg Gly His Arg Ile

370 375 380

Glu Leu Ala Glu Val Glu His Val Ile Leu Asp Asn Ser Leu Val Gln

385 390 395 400

Asp Ala Ala Val

<210> 12

<211> 69

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 12

Ile Glu Thr Ile Leu Cys Glu Glu Tyr Ala Glu Val Leu Gly Val Glu

1 5 10 15

Val Gly Val Met Asp Asn Phe Phe Asp Leu Gly Gly His Ser Leu Met

20 25 30

Ala Thr Lys Leu Ala Ala Arg Ala Thr Arg Arg Leu Asp Ala Lys Leu

35 40 45

Ser Val Lys Asp Ile Phe Asp Tyr Pro Ile Leu Ala Asn Leu Ala Ala

50 55 60

Ala Val Gln Arg Gly

65

<210> 13

<211> 298

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 13

Gly Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp

1 5 10 15

Gln Leu Asn Val Gly Ser Asn Trp Tyr Leu Gln Pro Ile Ala Ile Arg

20 25 30

Ile Arg Gly Ser Leu Asn Ile Asn Ala Leu Thr Thr Ala Leu His Ala

35 40 45

Leu Glu Gln Arg His Glu Thr Leu Arg Thr Thr Phe Glu Glu Glu Asp

50 55 60

Gly Val Gly Met Gln Val Val Gln Glu Tyr Asp Pro Ile Glu Leu Arg

65 70 75 80

Ile Met Asp Ile Ala Ala Asp Tyr Asp Gly Asp Tyr Thr Glu Ala Leu

85 90 95

Lys Gly Glu Gln Thr Thr Pro Phe Asp Leu Glu Ser Glu Pro Gly Trp

100 105 110

Arg Val Ser Leu Leu Arg Met Asn Asp Asn Asp His Ile Leu Ser Leu

115 120 125

Val Leu His His Ile Ile Ser Asp Gly Trp Ser Val Asp Val Leu Arg

130 135 140

Gln Glu Leu Lys Gln Phe Tyr Ala Ala Ala Leu Gln Gly Leu Asp Pro

145 150 155 160

Leu Ser Gly Ala Asp Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ser Leu

165 170 175

Trp Gln Lys Gln Pro Glu Gln Val Ala Glu His Glu Arg Gln Leu Lys

180 185 190

Tyr Trp Val Glu Gln Leu Ala Asp Asn Ser Pro Ala Thr Leu Leu Ala

195 200 205

Asp Arg Pro Arg Pro Ser Val Leu Ser Gly Gln Ala Gly Ser Val Pro

210 215 220

Leu Ser Ile Glu Gly Gln Val Tyr Glu Lys Leu Gln Ala Phe Cys Arg

225 230 235 240

Ala His Gln Thr Thr Ser Phe Ser Val Leu Leu Ala Ala Phe Arg Ala

245 250 255

Ala His Phe Arg Leu Thr Gly Val Asp Asp Ala Thr Ile Gly Ile Pro

260 265 270

Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu His Leu Ile Gly Phe Phe

275 280 285

Val Asn Arg Gln Cys Met Arg Ile Thr Val

290 295

<210> 14

<211> 403

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 14

Leu Thr Tyr Ala Gln Leu Asp Gln Gln Ser Asp Glu Ile Ala Thr Trp

1 5 10 15

Leu Arg Asn Lys Lys Met Ala Pro Glu Thr Leu Val Gly Val Leu Ala

20 25 30

Pro Arg Ser Cys Gln Thr Ile Val Ala Phe Leu Gly Val Leu Lys Ala

35 40 45

Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Ala Pro Met Ala Arg Val

50 55 60

Glu Thr Ile Met Ser Ser Val Pro Gly Ser Lys Leu Leu Leu Leu Gly

65 70 75 80

Ser Asp Val Pro Ala Gln Glu Ile Gln Leu Gln Asn Val Glu Leu Val

85 90 95

Arg Ile Glu Asp Thr Leu Gly His Ala Ala Ser Ala Gly Thr Ala Thr

100 105 110

Thr Glu Pro Ser Pro Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly

115 120 125

Ser Thr Gly Lys Pro Lys Gly Val Met Val Glu His Arg Ser Val Ile

130 135 140

Arg Leu Val Arg Lys Glu Ser Asn Ser Met Ser Lys Met Ser Ser Arg

145 150 155 160

Ala Arg Val Ala His Leu Thr Asn Ile Ala Phe Asp Val Ser Ala Trp

165 170 175

Glu Val Tyr Ala Thr Leu Leu Asn Gly Gly Thr Leu Val Cys Val Asp

180 185 190

Tyr Phe Thr Ser Phe Asp Ala Lys Ala Leu Gly Leu Leu Phe Glu Arg

195 200 205

Glu Gln Ile Thr Ala Ala Met Ile Thr Pro Thr Leu Leu Lys Gln Cys

210 215 220

Ile Thr Ile Val Pro Glu Ala Leu Arg Lys Leu Ser Val Leu Tyr Thr

225 230 235 240

Gly Gly Asp Arg Phe Asp Arg Arg Asp Ala Ile Ala Thr Lys Ala Leu

245 250 255

Val Lys Gly Pro Val Tyr Asn Ala Trp Gly Pro Thr Glu Thr Thr Ile

260 265 270

Val Ser Thr Ile Tyr Glu Leu Ala Asp Asp Asp Gln Phe Thr Asn Gly

275 280 285

Val Pro Ile Gly Lys Ala Val Ser Asn Ser Trp Ala Tyr Val Met Asp

290 295 300

Leu Asn Gln Gln Leu Val Pro Val Gly Val Met Gly Glu Ala Val Val

305 310 315 320

Ile Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro Ala Leu Asp Cys

325 330 335

Asn Arg Phe Val His Ile Thr Ile Asp Gly Lys Arg Val Arg Ala Tyr

340 345 350

Arg Thr Gly Asp Arg Ala Arg Tyr Arg Pro Lys Asp Gly Glu Ile Glu

355 360 365

Phe Phe Gly Arg Met Asp Arg Gln Leu Lys Ile Arg Gly His Arg Ile

370 375 380

Glu Pro Ala Glu Ile Glu His Ala Met Leu Gly His Asn Asp Ile Val

385 390 395 400

Asp Val Ala

<210> 15

<211> 224

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 15

Asp Gly Gly Ala Ile Asp Gln Ala Glu Met Gln Glu Trp Leu Asp Asp

1 5 10 15

Thr Ile Gln Thr Ile Val Asp Gly Gln Pro Ala Gly His Val Phe Glu

20 25 30

Ile Gly Thr Gly Thr Gly Met Ile Met Phe Gly Leu Gly Lys Gln Gly

35 40 45

Leu Gln Ser Tyr Val Gly Leu Glu Pro Ser Thr Ser Ala Thr Thr Tyr

50 55 60

Val Asn Arg Lys Ile Lys Thr Ala Pro Thr Val Ala Gly Lys Ala Lys

65 70 75 80

Val Tyr Val Gly Thr Ala Met Glu Ala Ala Gln Leu Asn Gly Leu His

85 90 95

Pro Glu Val Val Val Ile Asn Ser Val Ala Gln Tyr Phe Pro Thr Pro

100 105 110

Glu Tyr Leu Leu Glu Val Val Gly Ile Leu Thr Gln Met Pro Gly Val

115 120 125

Lys Arg Leu Phe Phe Gly Asp Ile Arg Ser Tyr Ala Thr Asn Arg Lys

130 135 140

Phe Leu Ala Ala Arg Ala Leu His Met Leu Gly Ser Asn Ala Lys Lys

145 150 155 160

His Asp Ile Arg Arg Lys Met Ala Glu Leu Asp Glu Phe Glu Glu Glu

165 170 175

Leu Ile Val Asp Pro Ser Phe Phe Thr Gly Leu Val Ser Arg Leu Pro

180 185 190

Gly Gln Val Lys His Val Glu Ile Leu Pro Lys Gln Met Ile Ala Thr

195 200 205

Asn Glu Leu Ser Ala Tyr Arg Tyr Ala Ala Val Val His Leu Ala Leu

210 215 220

<210> 16

<211> 69

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 16

Val Glu Ala Val Leu Cys Glu Glu Phe Ser Glu Val Leu Gly Val Glu

1 5 10 15

Val Gly Val Thr Asp Asn Phe Phe Asp Leu Gly Gly His Ser Leu Met

20 25 30

Ala Thr Lys Leu Ala Ala Arg Thr Gly Arg Arg Leu Asp Ala Lys Val

35 40 45

Ser Val Lys Asp Val Phe Asp His Pro Val Leu Ala Asp Leu Ala Ala

50 55 60

Ala Ile Gln Arg Gly

65

<210> 17

<211> 298

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 17

Gly Pro Val Glu Gln Ser Tyr Ala Gln Gly Arg Leu Trp Phe Leu Glu

1 5 10 15

Gln Leu Asn Phe Lys Ala Thr Trp Tyr Leu Leu Pro Leu Ala Val Arg

20 25 30

Ile Arg Gly Pro Leu Asn Ile Lys Ala Leu Thr Thr Ala Leu His Ala

35 40 45

Leu Glu Gln Arg His Glu Thr Leu Arg Thr Thr Phe Ile Glu Arg Asp

50 55 60

Gly Val Gly Lys Gln Ala Val Gln Pro Phe Gln Pro Lys Glu Leu Glu

65 70 75 80

Ile Val Asp Ile Ala Ala Asp His Gln Gly Asp Tyr Leu Lys Val Leu

85 90 95

Arg Asp Glu Gln Thr Thr Met Phe Asn Leu Ala Thr Gln Pro Gly Trp

100 105 110

Arg Val Thr Leu His Arg Val Asp Gln Asn Thr His Asn Leu Ser Ile

115 120 125

Val Met His His Ile Ile Ser Asp Gly Trp Ser Val Asp Val Leu Arg

130 135 140

His Glu Leu Arg Gln Phe Tyr Ala Ala Ala Leu Arg Gly Gln Asp Pro

145 150 155 160

Leu Ala His Ile Ser Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ser Leu

165 170 175

Trp Gln Lys Gln Pro Asp Gln Ile Ile Glu His Ala Lys Gln Leu Glu

180 185 190

Tyr Trp Thr Lys Gln Leu Ala Asp Ser Ser Pro Ala Glu Leu Pro Thr

195 200 205

Asp Leu Pro Arg Pro Ala Val Leu Ser Gly Lys Ala Gly Glu Val Ala

210 215 220

Leu Ser Val Lys Gly Pro Leu Tyr Glu Arg Leu Gln Ala Phe Cys Lys

225 230 235 240

Thr His Gln Thr Thr Ala Phe Ala Thr Leu Leu Ala Ala Phe Arg Ala

245 250 255

Thr His His Arg Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr Pro

260 265 270

Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Leu Ile Gly Phe Phe

275 280 285

Val Asn Ala Gln Cys Met Arg Ile Thr Ile

290 295

<210> 18

<211> 402

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 18

Leu Thr Tyr Ala Gln Leu Asn Glu Gln Ser Asp Lys Val Ala Ala Trp

1 5 10 15

Leu His Gln Cys Asn Leu Pro Thr Glu Thr Leu Val Ala Val Leu Ala

20 25 30

Pro Arg Ser Cys Gln Thr Val Val Ala Phe Leu Gly Ile Leu Lys Ala

35 40 45

Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro Ala Ala Arg Ile

50 55 60

Glu Ala Ile Leu Ser Glu Val Ser Gly His Ile Leu Val Leu Leu Gly

65 70 75 80

Ser His Val Ser Ala Pro Lys Ile Glu Leu Ala Asp Val Glu Phe Val

85 90 95

Lys Ile Asp Asn Thr Val Glu His Asn Leu Pro Gly Arg Ile Gly Ser

100 105 110

Ala Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser

115 120 125

Thr Gly Lys Pro Lys Gly Val Lys Val Glu His Arg Gly Ile Val Arg

130 135 140

Leu Val Lys Glu Ser Asn Val Val Ala Lys Met Pro Gln Ala Ala Arg

145 150 155 160

Ile Ala His Leu Ser Asn Ile Ala Phe Asp Ala Ala Thr Trp Glu Leu

165 170 175

Tyr Ala Ala Leu Leu Asn Gly Gly Thr Leu Val Cys Ile Asn Tyr Leu

180 185 190

Thr Thr Leu Asp Ser Lys Ala Leu Glu Ala Val Phe Glu Gln Glu Lys

195 200 205

Ile Gln Ala Ala Met Leu Pro Pro Ala Leu Leu Lys Gln Tyr Leu Val

210 215 220

Asn Ile Pro Ala Ala Ile Gly Ala Leu Glu Val Val Leu Val Ala Gly

225 230 235 240

Asp Arg Phe Asp Arg Arg Asp Ala Ala Ala Thr Gln Ala Leu Val Gly

245 250 255

Ala Gly Val Tyr Asn Ala Tyr Gly Pro Thr Glu Asn Thr Thr Leu Ser

260 265 270

Thr Ile Tyr Asn Val Val Gln Gly Asp Ala Asn Val Asn Gly Val Pro

275 280 285

Ile Gly Arg Pro Val Ser Asn Ser Gly Ala Tyr Ile Met Asn Met Asn

290 295 300

Gln Glu Leu Val Pro Ile Gly Val Ile Gly Glu Leu Val Val Val Gly

305 310 315 320

Asp Gly Val Ala Arg Gly Tyr Thr Asp Pro Ala Leu Asp Val Asn Arg

325 330 335

Phe Val Asn Val Thr Ile Glu Gly Gln Thr Met Arg Ala Tyr Arg Thr

340 345 350

Gly Asp Arg Ala Arg Tyr Arg Pro Lys Asp Ala Gln Ile Glu Phe Phe

355 360 365

Gly Arg Met Asp Gln Gln Ile Lys Ile Arg Gly His Arg Ile Glu Pro

370 375 380

Ala Glu Val Glu His Ala Leu Leu Asn Asn Asp Leu Leu Gln Asp Ala

385 390 395 400

Ala Val

<210> 19

<211> 222

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 19

Asp Gly Ser Ala Ile Asp Lys Ala Glu Met Gln Glu Trp Leu Asp Asp

1 5 10 15

Thr Met Gln Thr Ile Leu Asp Gly Arg Pro Ala Gly Arg Val Leu Glu

20 25 30

Ile Gly Thr Gly Thr Gly Met Ile Leu Phe Asn Leu Gly Glu Gly Leu

35 40 45

Gln Ser Tyr Val Gly Leu Glu Pro Ser Thr Ser Ala Ala Ala Phe Val

50 55 60

Asn Arg Arg Ile Gln Thr Leu Pro Ala Phe Ala Gly Lys Ala Glu Val

65 70 75 80

His Val Gly Thr Ala Thr Asp Ile Ser Gln Leu Gln Asp Leu Arg Pro

85 90 95

Glu Val Val Val Ile Asn Ser Val Ala Gln Tyr Phe Pro Ser Pro Glu

100 105 110

Tyr Leu Ser Lys Val Leu Tyr Ala Leu Ala Gln Ile Pro Gly Val Lys

115 120 125

Arg Leu Phe Phe Gly Asp Met Arg Ser Tyr Ala Ile Asn Asp Gln Phe

130 135 140

Leu Ala Ala Arg Ala Leu His Asn Ile Gly Ser Lys Ala Thr Lys Ser

145 150 155 160

Ala Ile Arg Ser Lys Met Val Asp Leu Glu Asn Ser Glu Glu Glu Leu

165 170 175

Leu Val Asp Pro Thr Phe Phe Thr Asn Leu Ala Thr Glu Leu Pro Glu

180 185 190

Val Glu His Val Glu Ile Leu Pro Lys Arg Met Gln Ala Thr Asn Glu

195 200 205

Leu Ser Ala Tyr Arg Tyr Ala Ala Val Val His Ile Arg Asp

210 215 220

<210> 20

<211> 69

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 20

Ile Glu Ala Ala Leu Cys Glu Val Phe Val Asp Leu Leu Gly Thr Glu

1 5 10 15

Val Ser Ile Thr Asp Asn Phe Phe Asn Leu Gly Gly His Ser Leu Met

20 25 30

Ala Thr Lys Leu Ala Ala Arg Ile Ser Arg Arg Leu Asp Ala Arg Ile

35 40 45

Ser Val Lys Asp Val Phe Asp Tyr Pro Val Leu Ala Asp Leu Ala Gly

50 55 60

Ala Val Gln Arg Gly

65

<210> 21

<211> 295

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 21

Gly Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp

1 5 10 15

Gln Leu Asn Ala Gly Ser Leu Trp Tyr Ile Gln Pro Ile Ala Val Arg

20 25 30

Val Arg Gly Ser Leu Asn Ile Gly Ala Leu Thr Thr Ala Leu Asn Ala

35 40 45

Leu Glu Lys Arg His Glu Pro Leu Arg Thr Thr Phe Glu Glu His Asp

50 55 60

Gly Ile Gly Val Gln Val Val Gln Pro His Gln Pro Lys Lys Leu Arg

65 70 75 80

Ile Val Asp Thr Val Ala Asn Tyr Gln Gly Asp Phe Ile Arg Ala Leu

85 90 95

Arg Lys Glu Gln Gln Thr Leu Phe Asn Leu Ala Thr Glu Pro Gly Trp

100 105 110

Arg Val Ser Leu Leu Arg Ile Gly Glu Asp Asp Asn Ile Leu Ser Ile

115 120 125

Val Met His His Ile Ile Ser Asp Gly Trp Ser Val Asp Ile Leu Arg

130 135 140

Gln Asp Leu Lys Leu Phe Tyr Ala Ala Ala Leu Lys Ser Gln Glu Pro

145 150 155 160

Gln Val Asp Ala Leu Pro Ile Gln Tyr Arg Asp Phe Ala Phe Trp Gln

165 170 175

Lys Gln Pro Glu Gln Val Ala Glu His Gln Arg Gln Leu Asp Tyr Trp

180 185 190

Ile Glu Gln Leu Lys Asp Ser Lys Pro Ala Glu Leu Ile Thr Asp Phe

195 200 205

Pro Arg Pro Glu Val Leu Ser Gly Thr Ala Gly Ile Val Gln Leu Ala

210 215 220

Val Asp Gly Gln Val Tyr Glu Gly Leu Arg Ala Phe Cys Arg Ile His

225 230 235 240

Gln Thr Thr Ser Phe Val Val Leu Leu Ala Ala Phe Arg Ala Ala His

245 250 255

Tyr Arg Leu Thr Gly Thr Glu Asp Ala Thr Ile Gly Ser Pro Ile Ala

260 265 270

Asn Arg Asn Arg Pro Glu Leu Glu Ser Leu Ile Gly Phe Phe Val Asn

275 280 285

Thr Gln Cys Met Arg Ile Met

290 295

<210> 22

<211> 406

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 22

Leu Thr Tyr Ala Gln Leu Asp Glu Glu Ser Asn Lys Val Ala Thr Trp

1 5 10 15

Leu Ser Gln Arg Gln Leu Ala Pro Glu Thr Leu Val Gly Val Leu Ala

20 25 30

Pro Arg Ser Cys Pro Thr Ile Val Thr Phe Phe Gly Ile Leu Lys Ala

35 40 45

Ser Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro Ser Ala Arg Ile

50 55 60

Glu Ala Ile Leu Ser Ala Val Pro Asp His Lys Leu Val Phe Leu Gly

65 70 75 80

Ala Asp Val Pro Asp Pro Glu Ala Pro Leu Val Asn Val Glu Leu Val

85 90 95

Arg Ile Asp Asp Ile Leu Arg Gln Ser Ile His Ala Ser Asn Ala Gly

100 105 110

Leu Leu Ala Asn His Pro Leu Ala Thr Ser Leu Ala Tyr Val Met Phe

115 120 125

Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Met Val Glu His Arg

130 135 140

Ser Ile Val Arg Leu Val Lys Glu Thr Asn Leu Val Pro Ala Val Glu

145 150 155 160

Ala Val Ser Ser Val Ala His Ile Ser Asn Val Ala Phe Asp Ala Ala

165 170 175

Thr Trp Glu Ile Tyr Ala Ala Leu Leu Asn Gly Gly Thr Thr Val Cys

180 185 190

Ile Asp His Ile Thr Val Leu Asp Pro Ala Lys Leu Ala Leu Val Phe

195 200 205

Ser Ser Glu Lys Ile Lys Ala Ala Phe Phe Ser Thr Ala Leu Leu Lys

210 215 220

Gln Arg Leu Tyr Glu Glu Pro Ser Thr Ile Thr Gly Leu Asp Leu Leu

225 230 235 240

Tyr Ala Gly Gly Glu Arg Met Arg Pro Gln Asp Ala Leu Lys Thr Arg

245 250 255

Glu Leu Val Arg Gly Ser Phe Cys His Val Tyr Gly Pro Thr Glu Asn

260 265 270

Thr Thr Phe Ser Thr Val Tyr Pro Met Gly Val Glu Glu Arg Cys Val

275 280 285

Asn Gly Leu Pro Ile Gly Arg Ala Val Ser His Ser Gly Ala Val Ile

290 295 300

Met Asp Ala Asn Gln Arg Leu Val Pro Leu Gly Val Met Gly Glu Leu

305 310 315 320

Val Val Thr Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro Ala Leu

325 330 335

Asn Arg Asp Arg Phe Val Glu Val Asn Ile His Gly Gln Val Leu Arg

340 345 350

Ala Tyr Arg Thr Gly Asp Gln Ala Arg Tyr Arg Pro Lys Asp Gly Gln

355 360 365

Ile Glu Phe Ser Gly Arg Met Asp Arg Gln Leu Lys Ile Arg Gly His

370 375 380

Arg Ile Glu Pro Ala Glu Val Glu His Ala Ile Leu Ser His Asp Asp

385 390 395 400

Ile Arg Asn Ala Val Val

405

<210> 23

<211> 221

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 23

Asp Gly Thr Ala Ile Asp Lys Ala Glu Met Gln Glu Trp Leu Asp Asp

1 5 10 15

Thr Met Arg Thr Leu His Asp Gly Arg Asp Pro Gly His Val Leu Glu

20 25 30

Val Gly Thr Gly Thr Gly Met Ile Leu Phe Asn Leu Gly Lys Gly Leu

35 40 45

Gln Ser Tyr Val Gly Leu Glu Pro Ser Thr Ser Ala Ala Ala Phe Val

50 55 60

Asn Arg Lys Ile Glu Thr Ile Ser Ser Leu Ala Gly Lys Ala Lys Val

65 70 75 80

Glu Ile Gly Thr Ala Thr Asp Val Gly Gln Leu Lys Asn Leu Arg Ser

85 90 95

Asp Leu Val Val Ile Asn Ser Val Ala Gln Tyr Phe Pro Ser Pro Glu

100 105 110

Tyr Leu Val Glu Ala Val Thr Ala Leu Val His Ile Pro Gly Val Lys

115 120 125

Arg Leu Phe Phe Gly Asp Met Arg Ser Tyr Ala Met Asn Lys Gln Phe

130 135 140

Leu Val Ala Arg Ala Leu Arg Thr Leu Gly Ala Lys Ala Asn Lys Asp

145 150 155 160

Asp Val Arg Arg Lys Met Val Glu Leu Glu Glu Phe Glu Glu Glu Leu

165 170 175

Leu Val Asp Pro Ala Phe Phe Thr Gly Leu Ala Asn Trp Leu Ser Glu

180 185 190

Val Glu His Val Glu Ile Leu Pro Lys Gln Met Thr Ser Thr Asn Glu

195 200 205

Leu Ser Ser Tyr Arg Tyr Ala Ala Ile Val His Leu Arg

210 215 220

<210> 24

<211> 69

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 24

Ile Glu Ala Leu Leu Cys Glu Glu Phe Ala Glu Val Leu Gly Val Glu

1 5 10 15

Val Gly Ile Asn Asp Asp Phe Phe Asp Leu Gly Gly His Ser Leu Met

20 25 30

Ala Thr Lys Leu Ala Ala Arg Ser Ser Arg Arg Phe Asp Ala Lys Val

35 40 45

Ser Val Lys Asp Val Phe Asp His Pro Ile Leu Ala Asp Leu Ala Ala

50 55 60

Ser Ile Gln Arg Gly

65

<210> 25

<211> 298

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 25

Gly Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Glu

1 5 10 15

Gln Leu Asn Val Ser Ser Thr Trp Tyr Leu Gln Pro Ile Ala Val Arg

20 25 30

Met Arg Gly Pro Leu Lys Ile Glu Ala Leu Ala Ala Ala Phe His Ala

35 40 45

Leu Glu Glu Arg His Glu Thr Leu Arg Thr Thr Phe Glu Glu His Asp

50 55 60

Gly Ile Gly Met Gln Val Val Gln Pro His Arg Pro Lys Glu Leu Arg

65 70 75 80

Val Ile Asp Val Gln Ala Glu His Asp Gly Asp Tyr Thr Gln Ala Leu

85 90 95

His Thr Glu Gln Thr Thr Thr Phe Asn Leu Glu Thr Glu Pro Gly Trp

100 105 110

Arg Val Ser Val Phe Arg Leu Asn Glu Asp Asp Asn Ile Leu Ser Ile

115 120 125

Val Met His His Ile Ile Ser Asp Gly Trp Ser Phe Asp Ile Leu Arg

130 135 140

Lys Glu Ile Arg Glu Phe Tyr Asn Ala Ala Leu Lys Gly Lys Asp Pro

145 150 155 160

Leu Ala Gln Met Ser Pro Leu His Ile Gln Tyr Arg Asp Phe Ser Val

165 170 175

Trp Gln Lys Gln Leu Asn Gln Ile Thr Glu His Lys Arg Gln Leu Asp

180 185 190

Tyr Trp Thr Lys Asn Leu Ala Asp Asn Thr Pro Ala Glu Leu Pro Thr

195 200 205

Asp Leu Pro Arg Pro Ala Val Leu Ser Gly Lys Ala Gly Val Ile Gln

210 215 220

Leu Ser Ile Thr Gly Pro Val Tyr Asp Arg Leu Arg Ala Phe Cys Arg

225 230 235 240

Val His Gln Thr Thr Leu Phe Thr Val Leu Leu Thr Val Phe Arg Ala

245 250 255

Thr His Tyr Arg Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr Pro

260 265 270

Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Leu Ile Gly Phe Phe

275 280 285

Val Asn Thr Gln Cys Met Arg Ile Thr Val

290 295

<210> 26

<211> 405

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 26

Leu Thr Tyr Ala Gln Leu Asp Leu His Ser Asp Glu Leu Ala Ser Trp

1 5 10 15

Leu Arg Gln Lys Lys Met Ala Pro Glu Thr Leu Val Gly Val Leu Ala

20 25 30

Pro Arg Ser Cys Gln Thr Ile Val Thr Phe Leu Gly Ile Leu Lys Ala

35 40 45

Ser Leu Ala Tyr Leu Pro Leu Asp Val Lys Val Pro Val Ala Arg Ile

50 55 60

Glu Ala Ile Leu Ser Ser Ile Ser Gly Gln Lys Leu Ile Leu Leu Gly

65 70 75 80

Gln Asp Val Pro Val Pro Glu Ile Gln Leu Pro Asp Val Asp Val Val

85 90 95

Pro Ile Ser Glu Ile Leu Gly Arg Ser Val Pro Ser Arg Ala Thr Asp

100 105 110

Lys Ser Leu Gly Pro Leu Ala Arg Asn Leu Ala Tyr Val Leu Phe Thr

115 120 125

Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Met Ile Glu His Arg Ser

130 135 140

Ile Val Arg Leu Val Lys Glu Thr Asn Leu Ile Ser Lys Leu Pro Asn

145 150 155 160

Ala Pro Arg Thr Ala His Leu Thr Asn Leu Val Phe Asp Asn Ser Ala

165 170 175

Trp Glu Ile Tyr Ser Thr Leu Leu Asn Gly Gly Thr Leu Val Cys Ile

180 185 190

Asp Tyr Ala Thr Val Leu Asp Ser Lys Ala Leu Glu Thr Val Phe Lys

195 200 205

Glu Gln Arg Ile Gln Thr Ser Leu Met Pro Pro Ala Leu Leu Lys Glu

210 215 220

Cys Leu Ala Asn Met Pro Thr Met Phe Asp Asp Val Glu Val Leu Tyr

225 230 235 240

Ala Leu Gly Asp Arg Phe Asp Lys Gln Asp Ala Met Lys Ala Arg Ser

245 250 255

Ile Val Lys Thr Ala Val Tyr Asn Ala Tyr Gly Pro Thr Glu Asn Thr

260 265 270

Val Ile Ser Thr Ile Tyr Glu Ile Ala Lys Asp Asp Ser Phe Val Asn

275 280 285

Gly Val Pro Ile Gly Arg Ser Ile Ser Asn Ser Gly Ala Phe Ile Met

290 295 300

Asp Ser Arg Gln Gln Leu Val Pro Val Gly Val Leu Gly Glu Leu Val

305 310 315 320

Val Ser Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro Thr Leu Asp

325 330 335

Val Asn Arg Phe Val Glu Val Thr Val Asp Gly Gln His Val Arg Val

340 345 350

Tyr Arg Thr Gly Asp Arg Val Arg Phe Arg Pro Lys Asp Gly Gln Ile

355 360 365

Glu Phe Phe Ser Arg Met Asp Gln Gln Val Lys Ile Arg Gly His Arg

370 375 380

Ile Glu Pro Ala Glu Val Glu His Val Ile Leu Thr Asn Lys Ile Ile

385 390 395 400

Arg Asp Ala Ala Val

405

<210> 27

<211> 69

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 27

Met Glu Arg Ile Leu Cys Glu Glu Phe Ala Asp Val Leu Gly Val Glu

1 5 10 15

Val Gly Ile Thr Asp Asn Phe Phe Asp Phe Gly Gly His Ser Leu Met

20 25 30

Ala Thr Lys Leu Ala Ala Arg Ile Ser Arg Arg Val Asn Ala Arg Val

35 40 45

Ser Val Lys Ser Val Phe Asp His Pro Val Leu Val Asp Leu Ala Ser

50 55 60

Thr Ile Lys Gln Asp

65

<210> 28

<211> 299

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 28

Gly Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp

1 5 10 15

Gln Leu Asn Phe Gly Ala Ser Trp Tyr Leu Met Pro Leu Ala Leu Arg

20 25 30

Leu Gln Gly Ser Leu His Val Lys Ser Leu Thr Thr Ala Leu Phe Ala

35 40 45

Leu Glu Gln Arg His Glu Thr Leu Arg Thr Thr Phe Glu Glu Gln Asp

50 55 60

Gly Val Gly Ile Gln Ile Val His Pro Ala Asn Lys Lys Asp Leu Arg

65 70 75 80

Ile Leu Asp Val Ser Lys Glu Gln Asn Ser Asp Tyr Ala Lys Val Leu

85 90 95

His Lys Glu Arg Thr Ile Pro Ile Asp Leu Thr Ser Glu Pro Gly Trp

100 105 110

Arg Val Ser Leu Ile Arg Leu Gly Glu Asp Asp His Ile Leu Ser Ile

115 120 125

Val Met His His Ile Ile Ser Asp Gly Trp Ser Val Asp Val Leu Arg

130 135 140

Gln Glu Leu Lys Gln Phe Tyr Thr Ala Ala Leu Lys Gly Gln Asp Pro

145 150 155 160

Leu Ala Gln Ile Asp Ala Leu Pro Ile Gln Tyr Arg Asp Phe Ser Leu

165 170 175

Trp Gln Lys Leu Pro Asp Gln Val Ala Glu His Gln Arg Gln Leu Glu

180 185 190

Tyr Trp Ala Glu Gln Leu Ala Asp Asn Thr Pro Ala Glu Leu Leu Thr

195 200 205

Asp Leu Pro Arg Pro Asp Val Leu Ser Gly Lys Ala Gly Ala Val Gln

210 215 220

Leu Thr Ile Asp Gly Pro Val Phe Asp Gln Leu Gln Ala Phe Cys Arg

225 230 235 240

Ala His Gln Thr Thr Met Phe Thr Val Leu Leu Ala Val Phe Arg Thr

245 250 255

Thr His Tyr Arg Leu Thr Gly Ala Thr Asp Ala Thr Ile Gly Thr Pro

260 265 270

Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Arg Leu Val Gly Phe Phe

275 280 285

Val Asn Thr Gln Cys Ile Arg Ile Thr Val Asp

290 295

<210> 29

<211> 403

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 29

Leu Thr Tyr Ser Gln Leu Asp Asp Gln Ser Asp Lys Ile Thr Ala Trp

1 5 10 15

Leu Leu Gln Arg Lys Ile Pro Ala Glu Ser Leu Val Ala Val Tyr Ala

20 25 30

Pro Arg Thr Cys Gln Thr Ile Ile Thr Phe Phe Gly Ile Leu Lys Ala

35 40 45

Asn Leu Ala Tyr Leu Pro Leu Asp Ile Asn Val Pro Ala Ala Arg Ile

50 55 60

Glu Ala Ile Leu Ser Thr Ile Ser Gly His Lys Leu Val Leu Leu Gly

65 70 75 80

Ser Gln Val Ser Ala Pro Ala Val Gln Leu Lys Asp Val Glu Tyr Val

85 90 95

Trp Ile Asp Glu Ala Met Ala Glu Thr Val Arg Thr Cys Thr Ser Pro

100 105 110

Glu Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser

115 120 125

Thr Gly Leu Pro Lys Gly Val Lys Val Glu His Arg Gly Val Val Arg

130 135 140

Leu Val Lys Gln Ser Asn Val Val Ala Lys Met Pro Gln Ala Ala Arg

145 150 155 160

Val Ala His Leu Ser Asn Ile Ala Phe Asp Ala Ala Thr Trp Glu Ile

165 170 175

Tyr Ala Ala Leu Leu Asn Gly Gly Ser Leu Ile Cys Ile Asp Tyr Phe

180 185 190

Thr Thr Leu Asp Ser Lys Glu Leu Glu Ala Val Phe Ala Arg Glu Lys

195 200 205

Ile Gln Ala Ala Met Leu Pro Pro Ala Leu Leu Lys Gln Cys Leu Val

210 215 220

Asn Ile Pro Ala Thr Ile Ser Ala Leu Asp Val Val Leu Ala Ala Gly

225 230 235 240

Asp Arg Phe Asp Arg Arg Asp Ala Ala Ala Thr Gln Ala Leu Val Gly

245 250 255

Gly Cys Val Tyr Asn Ala Tyr Gly Pro Thr Glu Asn Thr Thr Leu Ser

260 265 270

Thr Ile Tyr Asn Val Val Lys Gly Asp Ala Asn Val Asn Gly Val Pro

275 280 285

Ile Gly Arg Pro Val Ser Asn Ser Gly Ala Tyr Ile Met Asp Pro Asn

290 295 300

Gln Gln Leu Val Pro Lys Gly Val Met Gly Glu Leu Ile Val Val Gly

305 310 315 320

Asp Gly Val Ala Arg Gly Tyr Thr Asp Pro Ala Leu Asp Val Asn Arg

325 330 335

Phe Ile Glu Ile Ala Ile Asp Gly Asp Gln Ala Val Arg Ala Tyr Arg

340 345 350

Thr Gly Asp Arg Ala Arg Tyr Arg Pro Lys Asp Gly Gln Ile Glu Phe

355 360 365

Phe Gly Arg Met Asp Gln Gln Ile Lys Ile Arg Gly His Arg Ile Glu

370 375 380

Pro Ala Glu Val Glu His Ala Val Leu Asp Asn Ser Met Val Gln Asp

385 390 395 400

Ala Ala Val

<210> 30

<211> 225

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 30

Asp Gly Ser Ala Ile Asp Lys Asp Glu Met Gln Glu Trp Leu Asp Asp

1 5 10 15

Thr Met Ser Thr Leu Leu Asp Gly Arg Gln Pro Gly His Val Leu Glu

20 25 30

Ile Gly Thr Gly Thr Gly Met Ile Leu Phe Asn Leu Ala Glu Arg Met

35 40 45

Gly Leu Lys Ser Tyr Val Gly Leu Asp Pro Ser Glu Lys Ala Thr Ser

50 55 60

Phe Val Lys Gln Ala Ile Lys Ser Arg Pro Ser Leu Ala Gly Lys Ala

65 70 75 80

Glu Val His Val Gly Thr Ala Thr Asp Val Ala Arg Met Arg Asp Leu

85 90 95

His Pro Glu Val Val Val Ile Asn Ser Val Ala Gln Tyr Phe Pro Ser

100 105 110

Pro Glu Tyr Leu Ala Asp Val Val Gly Ala Leu Val Arg Ile Pro Gly

115 120 125

Val Lys Arg Leu Phe Phe Gly Asp Ile Arg Ser Tyr Ala Thr Asn Asn

130 135 140

His Phe Leu Ala Ala Arg Ala Leu His Lys Leu Gly Glu Lys Ala Thr

145 150 155 160

Arg Asp Thr Val Arg Ser Lys Met Ala Glu Leu Glu Gly Tyr Glu Glu

165 170 175

Glu Leu Leu Val Asp Pro Thr Phe Phe Thr Ser Leu Thr Ala Lys Leu

180 185 190

His Gly Gln Val Glu His Val Glu Ile Leu Pro Lys Arg Met Gln Ala

195 200 205

Thr Asn Glu Leu Ser Ala Tyr Arg Tyr Ala Ala Ile Val Tyr Ile Arg

210 215 220

Asp

225

<210> 31

<211> 69

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 31

Val Glu Ala Val Leu Cys Glu Glu Phe Thr Asp Val Leu Gly Val Glu

1 5 10 15

Val Gly Ile Thr Asp Asn Phe Phe Asp Leu Gly Gly His Ser Leu Met

20 25 30

Ala Thr Lys Leu Ala Ala Arg Ile Ser Lys His Leu Asp Ala Arg Val

35 40 45

Ser Val Lys Asp Val Phe Asp Tyr Pro Val Val Ala Asp Leu Ala Ala

50 55 60

Ser Ile Glu Arg Asn

65

<210> 32

<211> 296

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 32

Gly Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp

1 5 10 15

Gln Leu Asn Met Gly Val Ser Glu Leu Tyr Leu Met Pro Leu Ala Leu

20 25 30

Arg Leu Arg Gly Pro Leu Arg Val Asp Ala Phe Ala Ala Ala Val Ser

35 40 45

Ala Leu Glu Ala Arg His Glu Thr Leu Arg Thr Thr Phe Met Asp His

50 55 60

Asp Gly Val Gly Met Gln Val Ile Leu Pro Ser Asn Ser Lys Lys Leu

65 70 75 80

Arg Val Ile Asp Ala Ser Glu Asn Asp Tyr Ile Asp Ile Leu Arg Gln

85 90 95

Glu Arg Thr Ala Pro Phe Asn Leu Thr Thr Glu Pro Gly Phe Arg Ile

100 105 110

Ala Leu Leu Gln Leu Gly Gln Thr Asp Phe Ile Leu Ser Ile Val Met

115 120 125

His His Ile Ile Tyr Asp Gly Trp Ser Ile Asp Val Leu Cys Arg Glu

130 135 140

Leu Gly Arg Phe Tyr Ser Ala Ala Leu Gln Gly Gln Asp Pro Leu Ala

145 150 155 160

Gln Val Ser Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ser Ile Trp Gln

165 170 175

Lys Arg Pro Glu Gln Val Ala Glu His Glu Arg Gln Leu Gln Tyr Trp

180 185 190

Thr Glu Gln Leu Ala Asp Ser Ser Pro Ala Glu Leu Leu Thr Asp Leu

195 200 205

Pro Arg Pro Leu Val Pro Thr Gly Lys Ala Gly Ile Val Gln Leu Thr

210 215 220

Ile Glu Gly Ala Val Tyr Glu Arg Leu Arg Ala Phe Cys Arg Val His

225 230 235 240

Gln Thr Thr Ser Phe Ala Val Leu Leu Ala Ala Phe Arg Ala Thr His

245 250 255

Tyr Arg Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Ser Pro Ile Ala

260 265 270

Asn Arg Asn Arg Pro Glu Leu Glu Ser Leu Ile Gly Phe Phe Val Asn

275 280 285

Thr Gln Cys Ile Arg Val Thr Ile

290 295

<210> 33

<211> 405

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 33

Leu Thr Tyr Ala Gln Leu Asp Glu Lys Ser Asp Gln Leu Ala Ala Trp

1 5 10 15

Leu Cys Gln His Asn Ile Pro Ala Glu Thr Ile Val Gly Val Leu Ala

20 25 30

Pro Arg Ser Cys Glu Thr Ile Ile Ala Phe Leu Gly Ile Leu Lys Ala

35 40 45

Asn Leu Ala Tyr Leu Pro Leu Asp Asp Asn Val Pro Ala Ala Arg Ile

50 55 60

Glu Thr Ile Leu Ser Ala Val Pro Gly His Thr Leu Val Leu Leu Gly

65 70 75 80

Ser His Val Ala Ala Pro Ser Ile Gly Leu Ala Asp Ala Glu Phe Val

85 90 95

Asn Ile Asn His Thr Leu Gly His Ser Leu Gln Leu Asn Ser Thr Cys

100 105 110

Ala Lys Leu Gln Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr

115 120 125

Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Met Ile Glu His Arg Ser

130 135 140

Ile Val Arg Leu Val Lys Asn Ser Asn Thr Leu Ala Lys Leu Pro Arg

145 150 155 160

Ala Ala Arg Val Ala His Gln Phe Asn Leu Ala Phe Asp Ala Ala Asn

165 170 175

Tyr Glu Ile Tyr Gly Thr Leu Leu Asn Gly Gly Ala Leu Ile Cys Val

180 185 190

Asp Tyr Ser Thr Leu Leu Asp Ile Asp Ala Leu Val Ala Met Phe Lys

195 200 205

Arg Glu Lys Ile Thr Ala Ser Ser Leu Ser Pro Gly Leu Leu Lys Gln

210 215 220

Cys Val Asn Ser Ala Pro Glu Met Leu Lys Ala Leu Gln Val Ile Tyr

225 230 235 240

Thr Gly Gly Asp Arg Leu Asp Gly Arg Asp Ala Ile Glu Leu Gln Ala

245 250 255

Leu Val Pro Gly Gly Val Tyr Asn Met Tyr Gly Pro Thr Glu Asn Thr

260 265 270

Val Ile Ser Thr Leu Tyr Asn Leu Gly Asp Lys His Ser Tyr Val Asn

275 280 285

Gly Val Pro Ile Gly Thr Thr Val Ser Asn Ser Gly Ala Tyr Val Met

290 295 300

Asp Ala Leu Gln Gln Leu Val Pro Val Gly Val Met Gly Glu Leu Val

305 310 315 320

Val Thr Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro Glu Leu Asp

325 330 335

Arg Asn Arg Phe Ile Lys Val Asn Ile Asp Gly Gln Val Val Arg Ala

340 345 350

Tyr Arg Thr Gly Asp Arg Val Arg Tyr Arg Arg Ile Asp Gly Gln Leu

355 360 365

Glu Phe Phe Gly Arg Met Asp Gln Gln Ile Lys Ile Arg Gly Phe Arg

370 375 380

Ile Glu Thr Ala Glu Val Glu Asn Ala Met Leu Ser His Ser Ala Val

385 390 395 400

Arg Asn Ala Ala Val

405

<210> 34

<211> 67

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 34

Leu Glu Ala Ser Leu Cys Lys Glu Phe Ala Glu Val Leu Gly Val Glu

1 5 10 15

Val Gly Ile Thr Asp Asn Phe Phe Asp Leu Gly Gly His Ser Leu Leu

20 25 30

Ala Thr Lys Leu Ala Ala Arg Ile Ser Arg Arg Leu Asp Thr Arg Val

35 40 45

Ser Val Lys Asp Val Phe Asp Gln Pro Val Pro Ala Asp Leu Ala Leu

50 55 60

Lys Val Ser

65

<210> 35

<211> 277

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 35

Val Asp Val Tyr Pro Val Thr Trp Ile Gln Lys His Phe Leu Val Asp

1 5 10 15

Pro Ala Thr Gly Leu Pro Arg Thr Pro Ser Leu Phe Phe Val Asp Phe

20 25 30

Pro Ala Asn Ala Asp Cys Asp Lys Ile Cys Asn Ala Ser Arg Ser Leu

35 40 45

Ile Gln Leu Phe Asp Ile Phe Arg Thr Val Phe Val Gln Ala Ala Gly

50 55 60

Asn Phe Tyr Gln Val Val Leu Glu Glu Leu Asp Ile Pro Ile Ser Val

65 70 75 80

Ile Glu Thr Glu Asp Ile Ser Thr Ala Thr Arg Val Leu Lys Glu Gln

85 90 95

Asp Gln Gln Asn Pro Leu Gln Phe Gly Gln Gly Phe Leu Arg Phe Ala

100 105 110

Val Val Lys Thr Arg Ser Ala Val Arg Leu Val Leu Arg Ile Ser His

115 120 125

Cys Leu Tyr Asp Gly Leu Ser Phe Glu His Val Val Gln Ser Leu His

130 135 140

Ala Leu Tyr Asn Gly Asp Arg Ile Pro Thr Gln Pro Lys Phe Val Gln

145 150 155 160

Tyr Val Gln His Leu Thr Asp Ser Arg Lys Glu Gly Tyr Asp Phe Trp

165 170 175

Leu Ser Val Leu Glu Glu Ser Ser Met Thr Val Val Glu Thr Gly Arg

180 185 190

Arg Ala Gln Gln Leu Ser Ser Pro Glu Gly Ala Trp Phe Val Glu Lys

195 200 205

Ile Ile Lys Ala Val Ile Pro Ala Asn Ser Asp Gly Ile Thr Gln Ala

210 215 220

Thr Val Phe Thr Thr Ala Ser Thr Ile Leu Leu Ala Arg Met Thr Gly

225 230 235 240

Ser Ser Asp Ile Thr Phe Ser Arg Leu Val Ser Gly Arg Gln Ser Leu

245 250 255

Pro Ile Asn Asp Gln His Ile Val Gly Pro Cys Thr Asn Ile Val Pro

260 265 270

Val Arg Ile Arg Met

275

<210> 36

<211> 39126

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(39126)

<400> 36

atg gcc agc gac atc aat act cat cca gag gga gcg acc aag ttt tgg 48

Met Ala Ser Asp Ile Asn Thr His Pro Glu Gly Ala Thr Lys Phe Trp

1 5 10 15

cag caa cac ttt gac ggc ttg aac gcc tct gtg ttt cct gct ctg tcc 96

Gln Gln His Phe Asp Gly Leu Asn Ala Ser Val Phe Pro Ala Leu Ser

20 25 30

tcc cat ttg act gtc ccg cgt ccc aac gcg cag aca gca cat cgc att 144

Ser His Leu Thr Val Pro Arg Pro Asn Ala Gln Thr Ala His Arg Ile

35 40 45

tcc tat tca acc ttg gcg aag caa aaa tgg gac aac acc agc ctt tgc 192

Ser Tyr Ser Thr Leu Ala Lys Gln Lys Trp Asp Asn Thr Ser Leu Cys

50 55 60

cga gct gcg ctc gca ata ctg ctt gcc cgc tat tcg aat gca tct gaa 240

Arg Ala Ala Leu Ala Ile Leu Leu Ala Arg Tyr Ser Asn Ala Ser Glu

65 70 75 80

gca ctc ttc ggc gtc ttg gta gaa cag ttt ctc ccg tcc aac ggt gaa 288

Ala Leu Phe Gly Val Leu Val Glu Gln Phe Leu Pro Ser Asn Gly Glu

85 90 95

cag gca tcg aca gag gaa tca cca caa agc atc ctt ccc atc cgc atc 336

Gln Ala Ser Thr Glu Glu Ser Pro Gln Ser Ile Leu Pro Ile Arg Ile

100 105 110

cga ctt gac ctt gag gaa gct ggg ttg ggc ctt ttg caa gct atc aat 384

Arg Leu Asp Leu Glu Glu Ala Gly Leu Gly Leu Leu Gln Ala Ile Asn

115 120 125

acc cta gat gca tct ctg cgc gag tgg aag cat atc ggt ctt gac gcc 432

Thr Leu Asp Ala Ser Leu Arg Glu Trp Lys His Ile Gly Leu Asp Ala

130 135 140

att cgt ggc acg gga gag tac ggg tct gcc gga tgc gag ttc cag aca 480

Ile Arg Gly Thr Gly Glu Tyr Gly Ser Ala Gly Cys Glu Phe Gln Thr

145 150 155 160

gta ctt gct gtc act act gga aag acg cca cga acg cat aga ctc gcg 528

Val Leu Ala Val Thr Thr Gly Lys Thr Pro Arg Thr His Arg Leu Ala

165 170 175

tct tgc act gat cgc gcc ctt ttg ctc gat tgc cga atg gac gac gat 576

Ser Cys Thr Asp Arg Ala Leu Leu Leu Asp Cys Arg Met Asp Asp Asp

180 185 190

tcg gcc aca ctt ctc gca cgc tat gat ccc agt gtg att gat gac ctc 624

Ser Ala Thr Leu Leu Ala Arg Tyr Asp Pro Ser Val Ile Asp Asp Leu

195 200 205

cag gtc gcc cgt ttc cta aaa cag ctc ggg cac gtg att gag caa ttg 672

Gln Val Ala Arg Phe Leu Lys Gln Leu Gly His Val Ile Glu Gln Leu

210 215 220

cgt gtc cag gca gtc gat cta cct ctc tgg gaa ctt ggt att gtc acg 720

Arg Val Gln Ala Val Asp Leu Pro Leu Trp Glu Leu Gly Ile Val Thr

225 230 235 240

caa gaa gat agc gca gag att caa aaa tgg aac tcg cag caa ctc caa 768

Gln Glu Asp Ser Ala Glu Ile Gln Lys Trp Asn Ser Gln Gln Leu Gln

245 250 255

ttc agc cag gaa tgc ata cac gac gtg ttc gcc aac agg gtg gtt gat 816

Phe Ser Gln Glu Cys Ile His Asp Val Phe Ala Asn Arg Val Val Asp

260 265 270

acg ccg cag aaa atc gcc gta tcc gct tgg aac ggc gag cta acg ttt 864

Thr Pro Gln Lys Ile Ala Val Ser Ala Trp Asn Gly Glu Leu Thr Phe

275 280 285

gct gaa ctt gac agc ttc tcc tca tgc ctc gcc cag cac atc caa tcg 912

Ala Glu Leu Asp Ser Phe Ser Ser Cys Leu Ala Gln His Ile Gln Ser

290 295 300

ctt gaa ttg ggc gat gca aaa gcg ata ccg ctt tgc ttt gag aag tca 960

Leu Glu Leu Gly Asp Ala Lys Ala Ile Pro Leu Cys Phe Glu Lys Ser

305 310 315 320

aaa tgg gct atc gtc ggg atg ctc ggt gtg ctc aag gct ggc cga gca 1008

Lys Trp Ala Ile Val Gly Met Leu Gly Val Leu Lys Ala Gly Arg Ala

325 330 335

ttc aca ctg att gac cca tct aac cca ccc gct agg gct cgt caa atc 1056

Phe Thr Leu Ile Asp Pro Ser Asn Pro Pro Ala Arg Ala Arg Gln Ile

340 345 350

tgt cga caa aca gcc gcc acc att tcc atc gcg tct cca tac cag tgc 1104

Cys Arg Gln Thr Ala Ala Thr Ile Ser Ile Ala Ser Pro Tyr Gln Cys

355 360 365

gat atg atg cgc gct ctg gtg ccc gac tgc atc gtg gtc gac gac gac 1152

Asp Met Met Arg Ala Leu Val Pro Asp Cys Ile Val Val Asp Asp Asp

370 375 380

ttt ttc aag tca ttg gcg ttt gat aca gat caa ttc cag cct acg gca 1200

Phe Phe Lys Ser Leu Ala Phe Asp Thr Asp Gln Phe Gln Pro Thr Ala

385 390 395 400

acg ccg cag aca ttg gcc tac atc ctc ttc act tct ggt agt acc gga 1248

Thr Pro Gln Thr Leu Ala Tyr Ile Leu Phe Thr Ser Gly Ser Thr Gly

405 410 415

gag cca aaa ggc agt atg atg gag cat cac gga ttt gtg tct tgc tgt 1296

Glu Pro Lys Gly Ser Met Met Glu His His Gly Phe Val Ser Cys Cys

420 425 430

ctc gaa ttt ggt gcg gcg ctg ggc atc aac agc aac aca cgc gct ctt 1344

Leu Glu Phe Gly Ala Ala Leu Gly Ile Asn Ser Asn Thr Arg Ala Leu

435 440 445

caa ttt gcc tct tat gct ttc ggt gct tgc ctg cta gag att ttg acc 1392

Gln Phe Ala Ser Tyr Ala Phe Gly Ala Cys Leu Leu Glu Ile Leu Thr

450 455 460

acc cta atg cac ggc ggc acg gtc tgc atc cca tct gat gat gaa cgc 1440

Thr Leu Met His Gly Gly Thr Val Cys Ile Pro Ser Asp Asp Glu Arg

465 470 475 480

ata aat gat gca ccc ggg ttt atc aga cgc gca aac gtt aac tgg gca 1488

Ile Asn Asp Ala Pro Gly Phe Ile Arg Arg Ala Asn Val Asn Trp Ala

485 490 495

att ctc act cct tct ttc att ggc gcc atc cag ccc acc acc gta cct 1536

Ile Leu Thr Pro Ser Phe Ile Gly Ala Ile Gln Pro Thr Thr Val Pro

500 505 510

aac ctc aag acg ctg gta ttg gtg gga gaa gcc atg ccg tca gac ata 1584

Asn Leu Lys Thr Leu Val Leu Val Gly Glu Ala Met Pro Ser Asp Ile

515 520 525

cgc gat gtc tgg gcc tcg cac gtt cag ctt aaa aat gcc tat ggc cag 1632

Arg Asp Val Trp Ala Ser His Val Gln Leu Lys Asn Ala Tyr Gly Gln

530 535 540

agc gag agc gca acg atc tgt agc gta acg gaa gtc act ccc gcg acg 1680

Ser Glu Ser Ala Thr Ile Cys Ser Val Thr Glu Val Thr Pro Ala Thr

545 550 555 560

gtg gag gcg cac aat atc ggt cac gct gtg ggc gcc cga ttc tgg att 1728

Val Glu Ala His Asn Ile Gly His Ala Val Gly Ala Arg Phe Trp Ile

565 570 575

acc gac ccc aat aat ccc aac aaa ctt gcg cca atc ggc tgc gta ggc 1776

Thr Asp Pro Asn Asn Pro Asn Lys Leu Ala Pro Ile Gly Cys Val Gly

580 585 590

gag ctg ctt gtt gaa agt cct ggc atc gcg cgt gga tat ctg att cct 1824

Glu Leu Leu Val Glu Ser Pro Gly Ile Ala Arg Gly Tyr Leu Ile Pro

595 600 605

ctg cca gcg gac gca aca cct ttc att gac acg ctt cct gat tgg tac 1872

Leu Pro Ala Asp Ala Thr Pro Phe Ile Asp Thr Leu Pro Asp Trp Tyr

610 615 620

cca agg acg cag ccg ctc gac aac ttc aag ttc tac aga act ggc gat 1920

Pro Arg Thr Gln Pro Leu Asp Asn Phe Lys Phe Tyr Arg Thr Gly Asp

625 630 635 640

ctt gtc tgc tac cga tcc gac ggc acc gtg gtg tat ctg ggg cga cga 1968

Leu Val Cys Tyr Arg Ser Asp Gly Thr Val Val Tyr Leu Gly Arg Arg

645 650 655

gac tcg caa att aag atc cga gga cag cgc gtc gaa atc ggc gaa gta 2016

Asp Ser Gln Ile Lys Ile Arg Gly Gln Arg Val Glu Ile Gly Glu Val

660 665 670

gaa aca tgc ttg cga caa cag ctt ccc agt caa ctg gta cca gtt gtc 2064

Glu Thr Cys Leu Arg Gln Gln Leu Pro Ser Gln Leu Val Pro Val Val

675 680 685

gaa gct gtc agt ctg tcg ggc atg tcc aag agc atg acg ctg att gcc 2112

Glu Ala Val Ser Leu Ser Gly Met Ser Lys Ser Met Thr Leu Ile Ala

690 695 700

ttt ctg gtt ggc gaa aac acc att ctg gaa gag gac gtt tac gtt ttg 2160

Phe Leu Val Gly Glu Asn Thr Ile Leu Glu Glu Asp Val Tyr Val Leu

705 710 715 720

gag ggc agt gcc gcg cag cgc atc agt tcg aaa ctg cga cag att gta 2208

Glu Gly Ser Ala Ala Gln Arg Ile Ser Ser Lys Leu Arg Gln Ile Val

725 730 735

ccc ggg tac tgc att ccg tct cac tat att cgc atc aac cat ctt ccc 2256

Pro Gly Tyr Cys Ile Pro Ser His Tyr Ile Arg Ile Asn His Leu Pro

740 745 750

act acc gcc act gga aag tgt gat cgg aaa gca ctt cga gcc atc ggt 2304

Thr Thr Ala Thr Gly Lys Cys Asp Arg Lys Ala Leu Arg Ala Ile Gly

755 760 765

acc aaa ttg ctt agg gaa gcc gtg gag ggc atg gcg tca cag gag gaa 2352

Thr Lys Leu Leu Arg Glu Ala Val Glu Gly Met Ala Ser Gln Glu Glu

770 775 780

cag gag agt gct tcg tta atg acc gaa ggg att aca ctg gaa cgc atc 2400

Gln Glu Ser Ala Ser Leu Met Thr Glu Gly Ile Thr Leu Glu Arg Ile

785 790 795 800

tgg ttc cag agc ctg ggt ctc aag ccc aac tcc acg aga cac aaa tct 2448

Trp Phe Gln Ser Leu Gly Leu Lys Pro Asn Ser Thr Arg His Lys Ser

805 810 815

aac ttc ttc aat ctg ggc ggc gac tcc att gcg gca atc cgg atg gtg 2496

Asn Phe Phe Asn Leu Gly Gly Asp Ser Ile Ala Ala Ile Arg Met Val

820 825 830

aac atg gca cgg gca gca ggc ttg ttg ctg agc atc tcc gat atc ttt 2544

Asn Met Ala Arg Ala Ala Gly Leu Leu Leu Ser Ile Ser Asp Ile Phe

835 840 845

cag aac ccc tca ctg gcg ggg ctc atc aat gtg atg cag cag agc tcg 2592

Gln Asn Pro Ser Leu Ala Gly Leu Ile Asn Val Met Gln Gln Ser Ser

850 855 860

act gca caa gac gct att ccc gcc acc gag tac agc ggg ccg gtc gag 2640

Thr Ala Gln Asp Ala Ile Pro Ala Thr Glu Tyr Ser Gly Pro Val Glu

865 870 875 880

cag tcg ttt gca cag ggc cgt ttg tgg ttc ttg gat cag ctc acg acc 2688

Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp Gln Leu Thr Thr

885 890 895

ggc gca tcg tgg tac cta atg cca ctt gcg gtc cgc att cac ggg ccg 2736

Gly Ala Ser Trp Tyr Leu Met Pro Leu Ala Val Arg Ile His Gly Pro

900 905 910

ctc cgc gtc caa gcc ctt tcc agc gcc ctg cat gct ttg gag cag cgc 2784

Leu Arg Val Gln Ala Leu Ser Ser Ala Leu His Ala Leu Glu Gln Arg

915 920 925

cac gag acg cta cga acg acg ttc gag cag caa gac ggt atg ggc gtg 2832

His Glu Thr Leu Arg Thr Thr Phe Glu Gln Gln Asp Gly Met Gly Val

930 935 940

cag att gtc cac cca agc agc aag agg gag ctg cgc gtc atc gac gtg 2880

Gln Ile Val His Pro Ser Ser Lys Arg Glu Leu Arg Val Ile Asp Val

945 950 955 960

tcg ggt aag cag aac ggc ggc tac gat cag gtg ttg aag cga gag cag 2928

Ser Gly Lys Gln Asn Gly Gly Tyr Asp Gln Val Leu Lys Arg Glu Gln

965 970 975

aca aca ccc atc gac ttg gcc aaa gag ccc gga tgg aga gcc gcg ctg 2976

Thr Thr Pro Ile Asp Leu Ala Lys Glu Pro Gly Trp Arg Ala Ala Leu

980 985 990

cta cga gtg ggc gac gat gag cac atc ctc tcg att gtc atc cac cac 3024

Leu Arg Val Gly Asp Asp Glu His Ile Leu Ser Ile Val Ile His His

995 1000 1005

atc ata tac gac ggt tgg tcg ctg ggc gta ctg cgt gag gaa ctc 3069

Ile Ile Tyr Asp Gly Trp Ser Leu Gly Val Leu Arg Glu Glu Leu

1010 1015 1020

ggc gac ctt tat gcg gcg gcg ctg cga ggt ccc gat cca ctc gca 3114

Gly Asp Leu Tyr Ala Ala Ala Leu Arg Gly Pro Asp Pro Leu Ala

1025 1030 1035

cac atg gcc ccg ctc ccg atc cag tac cgc gac ttc tct gtt tgg 3159

His Met Ala Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ser Val Trp

1040 1045 1050

cag aag cag cca cag caa gtg gcg cag cac caa caa cag ctc gtg 3204

Gln Lys Gln Pro Gln Gln Val Ala Gln His Gln Gln Gln Leu Val

1055 1060 1065

tac tgg aca aag cag ctt gaa gac agc gcg cct gca gag ctg ctt 3249

Tyr Trp Thr Lys Gln Leu Glu Asp Ser Ala Pro Ala Glu Leu Leu

1070 1075 1080

acc gac ttc ccc cgc cct gcc gag tta tct ggc cgt gcc ggt gag 3294

Thr Asp Phe Pro Arg Pro Ala Glu Leu Ser Gly Arg Ala Gly Glu

1085 1090 1095

gtt cgt ttc act atc gaa ggc agt gtc ttc gac agc ctg ctc gct 3339

Val Arg Phe Thr Ile Glu Gly Ser Val Phe Asp Ser Leu Leu Ala

1100 1105 1110

ttt cgt cgc gtc cac cag acg aca tca ttt gcg gtg cta cta gcc 3384

Phe Arg Arg Val His Gln Thr Thr Ser Phe Ala Val Leu Leu Ala

1115 1120 1125

gtc ttc cgt gct gcc cac tat cgt ctc acc ggc aca gag gac gcc 3429

Val Phe Arg Ala Ala His Tyr Arg Leu Thr Gly Thr Glu Asp Ala

1130 1135 1140

aca atc ggc acg ccc atc gct aat cgt act cgt gct gag gtc gag 3474

Thr Ile Gly Thr Pro Ile Ala Asn Arg Thr Arg Ala Glu Val Glu

1145 1150 1155

aag ctc atc ggt ttc ttt gtc aac acg cag tgt atg cgc att gct 3519

Lys Leu Ile Gly Phe Phe Val Asn Thr Gln Cys Met Arg Ile Ala

1160 1165 1170

gtc gcc gac gat gac acc ttc gca tcg ctc gtc agt caa gtc tgg 3564

Val Ala Asp Asp Asp Thr Phe Ala Ser Leu Val Ser Gln Val Trp

1175 1180 1185

tcc gtc gcg act gcc gca ttc gag cat cag gat gtc ccc ttc gag 3609

Ser Val Ala Thr Ala Ala Phe Glu His Gln Asp Val Pro Phe Glu

1190 1195 1200

cgt atc gtg tcg gcg ctc ctg ccc ggc gcc aga gac aca tct cgc 3654

Arg Ile Val Ser Ala Leu Leu Pro Gly Ala Arg Asp Thr Ser Arg

1205 1210 1215

aac ccg ctg gcc cag ctc ctg ttt gcg ctc cat ctg gag cag gac 3699

Asn Pro Leu Ala Gln Leu Leu Phe Ala Leu His Leu Glu Gln Asp

1220 1225 1230

ctc gac aag atc aat ctc gag ggc ttg gcc tgc gag act gta ccc 3744

Leu Asp Lys Ile Asn Leu Glu Gly Leu Ala Cys Glu Thr Val Pro

1235 1240 1245

acg cca atg gcg act cgc ttc gac gtc gag ttc cat ctc ttc cag 3789

Thr Pro Met Ala Thr Arg Phe Asp Val Glu Phe His Leu Phe Gln

1250 1255 1260

gaa gac gac aga ctg aac ggc gtc gtc aac ttc tcc acg gac ctc 3834

Glu Asp Asp Arg Leu Asn Gly Val Val Asn Phe Ser Thr Asp Leu

1265 1270 1275

ttc gag ccc cag acc atc cac agc ctg gtc tct gtc ttt cag gag 3879

Phe Glu Pro Gln Thr Ile His Ser Leu Val Ser Val Phe Gln Glu

1280 1285 1290

atc ctg cgc cgc ggc ctc gac caa cca cag acg cct att gca cat 3924

Ile Leu Arg Arg Gly Leu Asp Gln Pro Gln Thr Pro Ile Ala His

1295 1300 1305

ctc cag ctg act gat ggg ctt gaa gag ctt cgc aat gcc ggc ctg 3969

Leu Gln Leu Thr Asp Gly Leu Glu Glu Leu Arg Asn Ala Gly Leu

1310 1315 1320

ctg gac atc aag agg atc gac tac ccg cgc gag gcg agc gtt gta 4014

Leu Asp Ile Lys Arg Ile Asp Tyr Pro Arg Glu Ala Ser Val Val

1325 1330 1335

gac atg ttc caa aag cag gta gcc gct tgc cct aac gtg act gcc 4059

Asp Met Phe Gln Lys Gln Val Ala Ala Cys Pro Asn Val Thr Ala

1340 1345 1350

gtc aaa gat tcg acc tcg cag ctc acg tat gct caa ctg gat cag 4104

Val Lys Asp Ser Thr Ser Gln Leu Thr Tyr Ala Gln Leu Asp Gln

1355 1360 1365

gag tct gac aag ata gcc gtt tgg ctg cgc aaa cgc aac att cca 4149

Glu Ser Asp Lys Ile Ala Val Trp Leu Arg Lys Arg Asn Ile Pro

1370 1375 1380

gcc gag aca ttg att gcg ctg cta gca cct cga tcc tgt gac tcc 4194

Ala Glu Thr Leu Ile Ala Leu Leu Ala Pro Arg Ser Cys Asp Ser

1385 1390 1395

gtg gct gcc ttc ctc ggt att ctc aaa gcc aat ctg gcc tat ctc 4239

Val Ala Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu

1400 1405 1410

cct ctg gat gtt aat gtc ccc gct gct cgt atc gag gca atc ctg 4284

Pro Leu Asp Val Asn Val Pro Ala Ala Arg Ile Glu Ala Ile Leu

1415 1420 1425

tca acc gta gca ggt cac aaa ctg gtc ttg ctc gga cga gat gtg 4329

Ser Thr Val Ala Gly His Lys Leu Val Leu Leu Gly Arg Asp Val

1430 1435 1440

cct ctg cta ggt acg cag ctg gcc gac ctc gag ctt gtc cgt atc 4374

Pro Leu Leu Gly Thr Gln Leu Ala Asp Leu Glu Leu Val Arg Ile

1445 1450 1455

ggc gag gcg ctg cgt ggc tcg agt tca ggg agt gtc gcc gcc gac 4419

Gly Glu Ala Leu Arg Gly Ser Ser Ser Gly Ser Val Ala Ala Asp

1460 1465 1470

aag gct att cga cct aca gca aca agc ctg gcc tac gtt atc ttc 4464

Lys Ala Ile Arg Pro Thr Ala Thr Ser Leu Ala Tyr Val Ile Phe

1475 1480 1485

acg tct gga tct act ggc cag cca aag ggt atc atg gtt cct cat 4509

Thr Ser Gly Ser Thr Gly Gln Pro Lys Gly Ile Met Val Pro His

1490 1495 1500

cgc agc ttg gtc aac gtg atc aag cag cga cct gcc tat gga aat 4554

Arg Ser Leu Val Asn Val Ile Lys Gln Arg Pro Ala Tyr Gly Asn

1505 1510 1515

gtc gct cac atg aca aat ctc gcc ttt gat ccc tcc ctg ttc gag 4599

Val Ala His Met Thr Asn Leu Ala Phe Asp Pro Ser Leu Phe Glu

1520 1525 1530

atg tgc act gcc ttg ttc aat ggc aat acg ctg att tgc atc gac 4644

Met Cys Thr Ala Leu Phe Asn Gly Asn Thr Leu Ile Cys Ile Asp

1535 1540 1545

aca ttg gta gca ctc gat gca act cag ctt cct acc atc ttc aag 4689

Thr Leu Val Ala Leu Asp Ala Thr Gln Leu Pro Thr Ile Phe Lys

1550 1555 1560

cag gaa gca att cgt gtc gca atg atg acg ccg gcc ttg ctc acc 4734

Gln Glu Ala Ile Arg Val Ala Met Met Thr Pro Ala Leu Leu Thr

1565 1570 1575

aga ctc cta gcc cag gct act gac gca ctg cat gaa cta gag gca 4779

Arg Leu Leu Ala Gln Ala Thr Asp Ala Leu His Glu Leu Glu Ala

1580 1585 1590

ctt tat gtt ctg gga gat cga ttc cct cca aaa gat gct gcc aga 4824

Leu Tyr Val Leu Gly Asp Arg Phe Pro Pro Lys Asp Ala Ala Arg

1595 1600 1605

gca agt gaa ctt gtc aaa acg gcc gta tac aat gcc tac gga ccg 4869

Ala Ser Glu Leu Val Lys Thr Ala Val Tyr Asn Ala Tyr Gly Pro

1610 1615 1620

agt gag aac tcc atc tgc aca act ctc ttc cat gct gcc act ggc 4914

Ser Glu Asn Ser Ile Cys Thr Thr Leu Phe His Ala Ala Thr Gly

1625 1630 1635

gcc atg tgt acc aat ggt gtg cct gtt ggc cga gta atc aac aac 4959

Ala Met Cys Thr Asn Gly Val Pro Val Gly Arg Val Ile Asn Asn

1640 1645 1650

tcg ggc gta tat gtt atg gat cca aag cag tcg ctt gtt tcc tac 5004

Ser Gly Val Tyr Val Met Asp Pro Lys Gln Ser Leu Val Ser Tyr

1655 1660 1665

ggc gtc atg ggt gag ctc gtc gtc gct ggc gaa ggc ctt gca att 5049

Gly Val Met Gly Glu Leu Val Val Ala Gly Glu Gly Leu Ala Ile

1670 1675 1680

gga tat acc aag cca gaa ctc aac gaa ggc cgc ttt ctg acg ctt 5094

Gly Tyr Thr Lys Pro Glu Leu Asn Glu Gly Arg Phe Leu Thr Leu

1685 1690 1695

aca atg gac gga aaa cct gta aga gcg ttt cgt acc gga gat cgt 5139

Thr Met Asp Gly Lys Pro Val Arg Ala Phe Arg Thr Gly Asp Arg

1700 1705 1710

gtt cga tac cgg ccg aca gat ggt caa ctg gaa ttt ttt ggc cgc 5184

Val Arg Tyr Arg Pro Thr Asp Gly Gln Leu Glu Phe Phe Gly Arg

1715 1720 1725

atg gac ttc caa att aag atc cga ggt cat cgt gtc gag ttg gct 5229

Met Asp Phe Gln Ile Lys Ile Arg Gly His Arg Val Glu Leu Ala

1730 1735 1740

gaa gtg gaa cga gtt ttg aac agg cac cct gcc atc aaa gac gcc 5274

Glu Val Glu Arg Val Leu Asn Arg His Pro Ala Ile Lys Asp Ala

1745 1750 1755

atc aca ctg ctg agg cag cac ggc tcc tca gca caa gac aca gag 5319

Ile Thr Leu Leu Arg Gln His Gly Ser Ser Ala Gln Asp Thr Glu

1760 1765 1770

ctt gtc agt ttt att gtg cta gga gag cag aag cct gta aag ccc 5364

Leu Val Ser Phe Ile Val Leu Gly Glu Gln Lys Pro Val Lys Pro

1775 1780 1785

cat cga aac gcc acc gac cat ggc gga atg gag att gag caa ttg 5409

His Arg Asn Ala Thr Asp His Gly Gly Met Glu Ile Glu Gln Leu

1790 1795 1800

gac caa aag cta gaa gca aac ctg cgt gcc atg atg cag gct acg 5454

Asp Gln Lys Leu Glu Ala Asn Leu Arg Ala Met Met Gln Ala Thr

1805 1810 1815

ctg ccc tca tac atg gtt ccc tcg aga atc ata gtg cta gac cat 5499

Leu Pro Ser Tyr Met Val Pro Ser Arg Ile Ile Val Leu Asp His

1820 1825 1830

atg ccg ctc gac aag aat gga aag gtt gac cga cga gga ttg aca 5544

Met Pro Leu Asp Lys Asn Gly Lys Val Asp Arg Arg Gly Leu Thr

1835 1840 1845

gga ctg acg ctg agc cca gcc atg gaa aca agc tcg cgt gtt gtt 5589

Gly Leu Thr Leu Ser Pro Ala Met Glu Thr Ser Ser Arg Val Val

1850 1855 1860

gtg gca gca cgg aac gag atc gag gcc gta ctg tgc gag gag ttt 5634

Val Ala Ala Arg Asn Glu Ile Glu Ala Val Leu Cys Glu Glu Phe

1865 1870 1875

gct cac atc ctt ggt gtt gaa att ggc gtc act gat aac ttc ttc 5679

Ala His Ile Leu Gly Val Glu Ile Gly Val Thr Asp Asn Phe Phe

1880 1885 1890

gac ctc ggc gga cat tca ctc atg gct act act ctc gct gct cgc 5724

Asp Leu Gly Gly His Ser Leu Met Ala Thr Thr Leu Ala Ala Arg

1895 1900 1905

ctc gct cgc cgt ctt aat gct agc att tcc gtc aag gat gtc ttc 5769

Leu Ala Arg Arg Leu Asn Ala Ser Ile Ser Val Lys Asp Val Phe

1910 1915 1920

gat cag cct att gtc gct aat ctc gcc gcc aca atc aag cga ggc 5814

Asp Gln Pro Ile Val Ala Asn Leu Ala Ala Thr Ile Lys Arg Gly

1925 1930 1935

tcg acc cct cac aat gca atc cct cca act aaa tac tct ggg ccg 5859

Ser Thr Pro His Asn Ala Ile Pro Pro Thr Lys Tyr Ser Gly Pro

1940 1945 1950

gtt gaa cag tcc ttc gca caa ggt cgt ctc tgg ttt ctg gac caa 5904

Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp Gln

1955 1960 1965

ctg aac ctt ggg gct gcc tgg tat cat atg cct ctt gca gtg cgt 5949

Leu Asn Leu Gly Ala Ala Trp Tyr His Met Pro Leu Ala Val Arg

1970 1975 1980

ttg cgc ggg cct ctc cat ctt gag gca ctc act gca gcg ctg cat 5994

Leu Arg Gly Pro Leu His Leu Glu Ala Leu Thr Ala Ala Leu His

1985 1990 1995

gcc ctt gag gag cgc cac gag acg tta cgg aca gta ttt gag gaa 6039

Ala Leu Glu Glu Arg His Glu Thr Leu Arg Thr Val Phe Glu Glu

2000 2005 2010

caa gat ggt gtg ggc atg cag atc gtc cgg cca agc agc aag acg 6084

Gln Asp Gly Val Gly Met Gln Ile Val Arg Pro Ser Ser Lys Thr

2015 2020 2025

ccg ctg cga ata atc gac gtg tcc act aaa gag cga ggt tat gcc 6129

Pro Leu Arg Ile Ile Asp Val Ser Thr Lys Glu Arg Gly Tyr Ala

2030 2035 2040

gag ttg ctc aag cag gag caa aca aca cca ttc gat cta gcc aca 6174

Glu Leu Leu Lys Gln Glu Gln Thr Thr Pro Phe Asp Leu Ala Thr

2045 2050 2055

gag tta ggg tgg agg gtg gct ctg ctg agg caa ggg aag gat gac 6219

Glu Leu Gly Trp Arg Val Ala Leu Leu Arg Gln Gly Lys Asp Asp

2060 2065 2070

cat att ctg tca att gtc att cac cac atc att tcc gac ggt tgg 6264

His Ile Leu Ser Ile Val Ile His His Ile Ile Ser Asp Gly Trp

2075 2080 2085

tct ctc gat atc ttg tgc gag gaa ctt ggt cag ttc tac gcc gct 6309

Ser Leu Asp Ile Leu Cys Glu Glu Leu Gly Gln Phe Tyr Ala Ala

2090 2095 2100

gtg ctc cgt ggc cag gac cca tta gcc caa ata agc cct ctg cct 6354

Val Leu Arg Gly Gln Asp Pro Leu Ala Gln Ile Ser Pro Leu Pro

2105 2110 2115

atc cag tat cgc gat ttc tct ctg tgg cag aag cag cct gag caa 6399

Ile Gln Tyr Arg Asp Phe Ser Leu Trp Gln Lys Gln Pro Glu Gln

2120 2125 2130

gtt gct gag cac cac cgg caa ctc gag tac tgg acc acc cag ctc 6444

Val Ala Glu His His Arg Gln Leu Glu Tyr Trp Thr Thr Gln Leu

2135 2140 2145

gag ggc agc gta cct gca gag ctt cta acc gat ctt cct cga cca 6489

Glu Gly Ser Val Pro Ala Glu Leu Leu Thr Asp Leu Pro Arg Pro

2150 2155 2160

acc ata cag tcc ggc aag gca ggc gtc atc cca ata acc gtc aac 6534

Thr Ile Gln Ser Gly Lys Ala Gly Val Ile Pro Ile Thr Val Asn

2165 2170 2175

ggc cct gta tac gag cgt cta cgg gcc ttc tct cga gct cat caa 6579

Gly Pro Val Tyr Glu Arg Leu Arg Ala Phe Ser Arg Ala His Gln

2180 2185 2190

acg acc gct ttt gcg gta ctg ttg gcc gcc ttt cga gca act cat 6624

Thr Thr Ala Phe Ala Val Leu Leu Ala Ala Phe Arg Ala Thr His

2195 2200 2205

tac cgt ctc tct gga gtc gca gac gct acc atc ggc acg cca atc 6669

Tyr Arg Leu Ser Gly Val Ala Asp Ala Thr Ile Gly Thr Pro Ile

2210 2215 2220

gcc aac cgt aat cga cct gaa ctg gag aat atg ata ggc ttt ttc 6714

Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Met Ile Gly Phe Phe

2225 2230 2235

gta aat gcc cag tgt atg cgt atc act gtc gag caa gac gat act 6759

Val Asn Ala Gln Cys Met Arg Ile Thr Val Glu Gln Asp Asp Thr

2240 2245 2250

ttt gag aca ctt gtc cgc cag atc cga ttt acg gca act gcc gcc 6804

Phe Glu Thr Leu Val Arg Gln Ile Arg Phe Thr Ala Thr Ala Ala

2255 2260 2265

ttt gcc aac caa gat gta ccc ttt gag cat atc gtc tca gcc ctt 6849

Phe Ala Asn Gln Asp Val Pro Phe Glu His Ile Val Ser Ala Leu

2270 2275 2280

atg cct gac tca cgc gat aca tcg cgg aat ccg cta gtg cag ctc 6894

Met Pro Asp Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu

2285 2290 2295

atg ttc gca ctc cac gcg tac aaa gat ctc ggc aag att gag ctt 6939

Met Phe Ala Leu His Ala Tyr Lys Asp Leu Gly Lys Ile Glu Leu

2300 2305 2310

gaa ggt tat gtt gca gag cct gtg cat aca act ctg tca acc cgc 6984

Glu Gly Tyr Val Ala Glu Pro Val His Thr Thr Leu Ser Thr Arg

2315 2320 2325

ttc gat ctc gaa ttc cac atg ttc cag gag aca aat cac ctc agc 7029

Phe Asp Leu Glu Phe His Met Phe Gln Glu Thr Asn His Leu Ser

2330 2335 2340

ggc tac gta ctg tat gca aca gac ttg ttc gag cct gag agc att 7074

Gly Tyr Val Leu Tyr Ala Thr Asp Leu Phe Glu Pro Glu Ser Ile

2345 2350 2355

gag ggg atg gtt tcc att ttt aaa gaa atc ctc gct cga gct ctt 7119

Glu Gly Met Val Ser Ile Phe Lys Glu Ile Leu Ala Arg Ala Leu

2360 2365 2370

gac caa ccc caa acc cca ctg gcg ctt cta ccg ctc acc gat ggg 7164

Asp Gln Pro Gln Thr Pro Leu Ala Leu Leu Pro Leu Thr Asp Gly

2375 2380 2385

ctg gct gaa ctt cgc agg agg ggg ctg ctt gag att gaa agg ccc 7209

Leu Ala Glu Leu Arg Arg Arg Gly Leu Leu Glu Ile Glu Arg Pro

2390 2395 2400

agc tat cct cgc gag tcg agc gtt gtt gac gtc ttc tgt agc cag 7254

Ser Tyr Pro Arg Glu Ser Ser Val Val Asp Val Phe Cys Ser Gln

2405 2410 2415

gta gcg gct tct ccc aac gca acc gct gtg aag gac tcg att tca 7299

Val Ala Ala Ser Pro Asn Ala Thr Ala Val Lys Asp Ser Ile Ser

2420 2425 2430

cag ctc act tac gct cag cta aat gag caa tct gac aag gtc gct 7344

Gln Leu Thr Tyr Ala Gln Leu Asn Glu Gln Ser Asp Lys Val Ala

2435 2440 2445

gct tgg cta cac cag tgc aac ctt cca act gaa act ttg gtc gct 7389

Ala Trp Leu His Gln Cys Asn Leu Pro Thr Glu Thr Leu Val Ala

2450 2455 2460

gtg cta gcg cct cga tct tgc caa aca gtt gtg gcc ttc ttg ggt 7434

Val Leu Ala Pro Arg Ser Cys Gln Thr Val Val Ala Phe Leu Gly

2465 2470 2475

att ctg aag gcc aac cta gca tat ctt ccc cta gac gtc aat gtt 7479

Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Val

2480 2485 2490

ccg gca gct cgc att gag gca att ctc tca gaa gtc tct ggc cac 7524

Pro Ala Ala Arg Ile Glu Ala Ile Leu Ser Glu Val Ser Gly His

2495 2500 2505

ata ctt gtc tta ctt gga tct cat gtt tct gct ccc aag att gag 7569

Ile Leu Val Leu Leu Gly Ser His Val Ser Ala Pro Lys Ile Glu

2510 2515 2520

ctc gct gat gtc gaa ttc gtc aaa att gac aac aca gtc gag cac 7614

Leu Ala Asp Val Glu Phe Val Lys Ile Asp Asn Thr Val Glu His

2525 2530 2535

aat ttg ccg ggc cgc att gga tct gct cca tct gcc acg agc ctc 7659

Asn Leu Pro Gly Arg Ile Gly Ser Ala Pro Ser Ala Thr Ser Leu

2540 2545 2550

gcc tat gtt att ttc aca tct gga tcg act ggc aag ccc aaa ggt 7704

Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly

2555 2560 2565

gtt aag gta gag cac cgc ggt att gtc cgc ctc gtt aaa gag agc 7749

Val Lys Val Glu His Arg Gly Ile Val Arg Leu Val Lys Glu Ser

2570 2575 2580

aat gta gta gca aaa atg cca caa gct gcg cgc att gct cac ttg 7794

Asn Val Val Ala Lys Met Pro Gln Ala Ala Arg Ile Ala His Leu

2585 2590 2595

tca aac att gcc ttt gac gcg gct acg tgg gaa tta tat gct gcg 7839

Ser Asn Ile Ala Phe Asp Ala Ala Thr Trp Glu Leu Tyr Ala Ala

2600 2605 2610

ttg ctc aac ggc ggc acc ctc gtc tgt atc aac tat tta acc acg 7884

Leu Leu Asn Gly Gly Thr Leu Val Cys Ile Asn Tyr Leu Thr Thr

2615 2620 2625

ctg gat agt aaa gca ctc gag gcc gtg ttt gag cag gaa aag atc 7929

Leu Asp Ser Lys Ala Leu Glu Ala Val Phe Glu Gln Glu Lys Ile

2630 2635 2640

caa gcg gct atg ctt cca cca gca ctg ctc aaa cag tat ttg gtt 7974

Gln Ala Ala Met Leu Pro Pro Ala Leu Leu Lys Gln Tyr Leu Val

2645 2650 2655

aac att ccc gca gct atc ggt gca cta gaa gtg gtc ctt gtc gct 8019

Asn Ile Pro Ala Ala Ile Gly Ala Leu Glu Val Val Leu Val Ala

2660 2665 2670

ggt gac cgt ttc gat cga cgc gat gct gca gcc acg cag gct ctt 8064

Gly Asp Arg Phe Asp Arg Arg Asp Ala Ala Ala Thr Gln Ala Leu

2675 2680 2685

gtt gga gca ggc gtg tat aac gcc tat gga ccg acg gag aat aca 8109

Val Gly Ala Gly Val Tyr Asn Ala Tyr Gly Pro Thr Glu Asn Thr

2690 2695 2700

aca ctc agc act atc tac aat gtc gtt cag ggc gat gcc aat gtg 8154

Thr Leu Ser Thr Ile Tyr Asn Val Val Gln Gly Asp Ala Asn Val

2705 2710 2715

aat ggc gtc ccg att gga cgc cct gtc agc aac tct ggc gcc tac 8199

Asn Gly Val Pro Ile Gly Arg Pro Val Ser Asn Ser Gly Ala Tyr

2720 2725 2730

atc atg aat atg aat cag gaa ctc gtt cct att ggc gtc ata ggc 8244

Ile Met Asn Met Asn Gln Glu Leu Val Pro Ile Gly Val Ile Gly

2735 2740 2745

gag ctg gtc gta gta gga gac ggt gtc gcc cga gga tac acc gac 8289

Glu Leu Val Val Val Gly Asp Gly Val Ala Arg Gly Tyr Thr Asp

2750 2755 2760

cca gcc ttg gac gtc aac cgc ttc gtc aac gtc act att gaa ggc 8334

Pro Ala Leu Asp Val Asn Arg Phe Val Asn Val Thr Ile Glu Gly

2765 2770 2775

caa act atg agg gct tat agg act ggc gat cgt gcc cgc tat agg 8379

Gln Thr Met Arg Ala Tyr Arg Thr Gly Asp Arg Ala Arg Tyr Arg

2780 2785 2790

ccc aaa gac gca cag att gaa ttc ttt ggc cga atg gat caa cag 8424

Pro Lys Asp Ala Gln Ile Glu Phe Phe Gly Arg Met Asp Gln Gln

2795 2800 2805

atc aag att cga ggc cat cgt att gag cca gct gag gtc gag cat 8469

Ile Lys Ile Arg Gly His Arg Ile Glu Pro Ala Glu Val Glu His

2810 2815 2820

gcg ttg ctc aac aat gac ttg ctt cag gac gct gca gtc att atc 8514

Ala Leu Leu Asn Asn Asp Leu Leu Gln Asp Ala Ala Val Ile Ile

2825 2830 2835

cga aag caa caa aat gat gag ctg gag atg gtt gct ttt gta gaa 8559

Arg Lys Gln Gln Asn Asp Glu Leu Glu Met Val Ala Phe Val Glu

2840 2845 2850

gca aac agc aat aag tcg atc gaa caa gag gcg agc aac caa gta 8604

Ala Asn Ser Asn Lys Ser Ile Glu Gln Glu Ala Ser Asn Gln Val

2855 2860 2865

gaa gac tgg ggc gct caa ttc gag agc aac gtc tac gcc gag atc 8649

Glu Asp Trp Gly Ala Gln Phe Glu Ser Asn Val Tyr Ala Glu Ile

2870 2875 2880

gag gca atc gat gcc tct gct gtt ggt aac gac ttc atg ggt tgg 8694

Glu Ala Ile Asp Ala Ser Ala Val Gly Asn Asp Phe Met Gly Trp

2885 2890 2895

act tcc atg tac gac ggc agc gcg atc gac aag gct gag atg cag 8739

Thr Ser Met Tyr Asp Gly Ser Ala Ile Asp Lys Ala Glu Met Gln

2900 2905 2910

gaa tgg ctc gat gat act atg cag aca ata ctt gat ggt cga cca 8784

Glu Trp Leu Asp Asp Thr Met Gln Thr Ile Leu Asp Gly Arg Pro

2915 2920 2925

gcc ggc cgc gtt ctc gaa atc ggc act ggc acg ggt atg atc ctc 8829

Ala Gly Arg Val Leu Glu Ile Gly Thr Gly Thr Gly Met Ile Leu

2930 2935 2940

ttc aat ctt ggt gaa ggg tta cag agc tat gtc ggt ctc gaa cca 8874

Phe Asn Leu Gly Glu Gly Leu Gln Ser Tyr Val Gly Leu Glu Pro

2945 2950 2955

tct acc tcg gcg gct gcg ttc gtc aat cgc agg att cag aca ctt 8919

Ser Thr Ser Ala Ala Ala Phe Val Asn Arg Arg Ile Gln Thr Leu

2960 2965 2970

cca gct ttc gct ggt aaa gct gaa gtt cac gtg ggt aca gcg aca 8964

Pro Ala Phe Ala Gly Lys Ala Glu Val His Val Gly Thr Ala Thr

2975 2980 2985

gat ata agc caa ctt caa gat ctc cgc ccg gaa gta gtg gtt atc 9009

Asp Ile Ser Gln Leu Gln Asp Leu Arg Pro Glu Val Val Val Ile

2990 2995 3000

aac tcg gtg gct cag tac ttc cca tcg cct gag tac ttg tct aag 9054

Asn Ser Val Ala Gln Tyr Phe Pro Ser Pro Glu Tyr Leu Ser Lys

3005 3010 3015

gtt ttg tac gca cta gcc caa att cct ggc gtc aag cgt ttg ttc 9099

Val Leu Tyr Ala Leu Ala Gln Ile Pro Gly Val Lys Arg Leu Phe

3020 3025 3030

ttt gga gac atg cga tct tac gcc atc aac gac cag ttc ctt gca 9144

Phe Gly Asp Met Arg Ser Tyr Ala Ile Asn Asp Gln Phe Leu Ala

3035 3040 3045

gct cgc gcc tta cac aac ata ggt agc aag gct act aag agc gcc 9189

Ala Arg Ala Leu His Asn Ile Gly Ser Lys Ala Thr Lys Ser Ala

3050 3055 3060

att cga agc aag atg gtc gat ctg gaa aac tct gag gaa gaa ttg 9234

Ile Arg Ser Lys Met Val Asp Leu Glu Asn Ser Glu Glu Glu Leu

3065 3070 3075

ctc gtc gac cca acc ttc ttc acc aac cta gcg acc gag ctt cca 9279

Leu Val Asp Pro Thr Phe Phe Thr Asn Leu Ala Thr Glu Leu Pro

3080 3085 3090

gag gtt gag cat gtt gag att ctg cca aaa cgc atg cag gct acc 9324

Glu Val Glu His Val Glu Ile Leu Pro Lys Arg Met Gln Ala Thr

3095 3100 3105

aac gaa ctt agc gcc tat cgt tat gca gct gtg gtg cac atc cgt 9369

Asn Glu Leu Ser Ala Tyr Arg Tyr Ala Ala Val Val His Ile Arg

3110 3115 3120

gat tca tcg gaa cga gct cag acc gtg cat gcc atc aaa tcg agc 9414

Asp Ser Ser Glu Arg Ala Gln Thr Val His Ala Ile Lys Ser Ser

3125 3130 3135

gca tgg gtc gac ttc agc aaa tct cag atg gac cgc aag gcc ctc 9459

Ala Trp Val Asp Phe Ser Lys Ser Gln Met Asp Arg Lys Ala Leu

3140 3145 3150

atc agt ctt ctt caa agc tcg gta aac acc gag gct gtt gct atc 9504

Ile Ser Leu Leu Gln Ser Ser Val Asn Thr Glu Ala Val Ala Ile

3155 3160 3165

ggc aat atc ccc tac agc aag act atc atg gcg cga cat gtc gtc 9549

Gly Asn Ile Pro Tyr Ser Lys Thr Ile Met Ala Arg His Val Val

3170 3175 3180

caa tcg ctt gac gaa gac aat gca gac aag gac att gcg caa gat 9594

Gln Ser Leu Asp Glu Asp Asn Ala Asp Lys Asp Ile Ala Gln Asp

3185 3190 3195

aaa ccc gat aag ccc acc tgg atc tcg gca gtt cgc tcc aat gcc 9639

Lys Pro Asp Lys Pro Thr Trp Ile Ser Ala Val Arg Ser Asn Ala

3200 3205 3210

gaa cac tgc cca tca cta tcg gct ctc gac ctt gta cag ctt ggt 9684

Glu His Cys Pro Ser Leu Ser Ala Leu Asp Leu Val Gln Leu Gly

3215 3220 3225

gag gag gca ggc ttc tgt gtg gag ctc agc tgg gct caa cag cga 9729

Glu Glu Ala Gly Phe Cys Val Glu Leu Ser Trp Ala Gln Gln Arg

3230 3235 3240

tct cat cac gga gca atc gac gca gtc ttt cat cat tac cag ccc 9774

Ser His His Gly Ala Ile Asp Ala Val Phe His His Tyr Gln Pro

3245 3250 3255

gct cga gaa gga agc cgt gtt ctg ttt cag ttc ccg acc gat acg 9819

Ala Arg Glu Gly Ser Arg Val Leu Phe Gln Phe Pro Thr Asp Thr

3260 3265 3270

tat cga cgc caa tcc ggt ccg ctt aca aac cga ccc ttg cag cga 9864

Tyr Arg Arg Gln Ser Gly Pro Leu Thr Asn Arg Pro Leu Gln Arg

3275 3280 3285

att cag agc cgg cga atg gaa aca cag gtt aga gaa aag cta cgg 9909

Ile Gln Ser Arg Arg Met Glu Thr Gln Val Arg Glu Lys Leu Arg

3290 3295 3300

gcc gtt ttg cct tca tac atg att cca tcg ctc atc gtg ctg gtc 9954

Ala Val Leu Pro Ser Tyr Met Ile Pro Ser Leu Ile Val Leu Val

3305 3310 3315

gac caa atg ccc ctg aac ccc aac ggc aaa gtg gat agg aag gcg 9999

Asp Gln Met Pro Leu Asn Pro Asn Gly Lys Val Asp Arg Lys Ala

3320 3325 3330

ttg gaa cga cga gcc cag gca gtg cta cgg gtc gaa aaa cca act 10044

Leu Glu Arg Arg Ala Gln Ala Val Leu Arg Val Glu Lys Pro Thr

3335 3340 3345

tcc gaa cgt gtt ggt gcc cgt aat gag act gag gct gtg ctt tgt 10089

Ser Glu Arg Val Gly Ala Arg Asn Glu Thr Glu Ala Val Leu Cys

3350 3355 3360

gag gag ttt acc gac gtt ctc gga ctt gag gtt ggt att acg gat 10134

Glu Glu Phe Thr Asp Val Leu Gly Leu Glu Val Gly Ile Thr Asp

3365 3370 3375

aac ttc ttc gac ctc ggt ggg cac tcg ctt atg gcg acc aaa ctc 10179

Asn Phe Phe Asp Leu Gly Gly His Ser Leu Met Ala Thr Lys Leu

3380 3385 3390

gcg gcc cgt atc agt cga cgc ctt gac gcc cgc gtc tct gtt aaa 10224

Ala Ala Arg Ile Ser Arg Arg Leu Asp Ala Arg Val Ser Val Lys

3395 3400 3405

gat gtc ttt gat cag cct gtc ata gtc gac ctc gcc gcc tcc att 10269

Asp Val Phe Asp Gln Pro Val Ile Val Asp Leu Ala Ala Ser Ile

3410 3415 3420

cgc cgt ggt tcg acc cct cac aat cct atc acc cca acc gag tat 10314

Arg Arg Gly Ser Thr Pro His Asn Pro Ile Thr Pro Thr Glu Tyr

3425 3430 3435

tct ggt ccg gta gag caa tcg ttt gct cag ggc cgt ctc tgg ttc 10359

Ser Gly Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe

3440 3445 3450

tta gac cag ttg aat ctc ggt gca tct tta tat ctc atg cct ctt 10404

Leu Asp Gln Leu Asn Leu Gly Ala Ser Leu Tyr Leu Met Pro Leu

3455 3460 3465

gcg ttg cgt ttg cgt gga cct ctc cgc atc gat gct ctc aca gct 10449

Ala Leu Arg Leu Arg Gly Pro Leu Arg Ile Asp Ala Leu Thr Ala

3470 3475 3480

gcg ctc ttc gca ttg gaa cag cga cac gag act ctc cga acc gtc 10494

Ala Leu Phe Ala Leu Glu Gln Arg His Glu Thr Leu Arg Thr Val

3485 3490 3495

ttc aag gag caa gat ggc gta ggc atc caa atc att caa cct agc 10539

Phe Lys Glu Gln Asp Gly Val Gly Ile Gln Ile Ile Gln Pro Ser

3500 3505 3510

caa aag aag aaa ctc aga acc att gat gta tct gca ggc gac ttt 10584

Gln Lys Lys Lys Leu Arg Thr Ile Asp Val Ser Ala Gly Asp Phe

3515 3520 3525

tcc gag gcg ctg cat cac gaa cgc act gcc cca ttt gat ctc gca 10629

Ser Glu Ala Leu His His Glu Arg Thr Ala Pro Phe Asp Leu Ala

3530 3535 3540

tca gag ccg ggc ttc aga gtc gcc ctt ctt cag ctt gag ccg tct 10674

Ser Glu Pro Gly Phe Arg Val Ala Leu Leu Gln Leu Glu Pro Ser

3545 3550 3555

gat cat gtg ctg tct atc gtc atg cac cat atc atc tac gac ggc 10719

Asp His Val Leu Ser Ile Val Met His His Ile Ile Tyr Asp Gly

3560 3565 3570

tgg tct atc gac att ttg tgt caa gaa ctg ggc cag ttc tac gct 10764

Trp Ser Ile Asp Ile Leu Cys Gln Glu Leu Gly Gln Phe Tyr Ala

3575 3580 3585

gct gca atc cag ggc cag gat cca ttg gga caa gtg agc ccg ctc 10809

Ala Ala Ile Gln Gly Gln Asp Pro Leu Gly Gln Val Ser Pro Leu

3590 3595 3600

cca att caa tac cgt gac ttc tct gtc tgg caa aag caa cct gag 10854

Pro Ile Gln Tyr Arg Asp Phe Ser Val Trp Gln Lys Gln Pro Glu

3605 3610 3615

cag gtc gct gag cat gag cgg cag ctt gcg tac tgg atc gat cag 10899

Gln Val Ala Glu His Glu Arg Gln Leu Ala Tyr Trp Ile Asp Gln

3620 3625 3630

ttg gcc gat agt gct ccc gct gag ttc ctt gtc gat ctc cca cgc 10944

Leu Ala Asp Ser Ala Pro Ala Glu Phe Leu Val Asp Leu Pro Arg

3635 3640 3645

cca ccc gtc ttg tct ggt gat gcc gga cta gtc cac ctc act atc 10989

Pro Pro Val Leu Ser Gly Asp Ala Gly Leu Val His Leu Thr Ile

3650 3655 3660

gat ggt ccc atc tat gac cgc ctg aga gcc ttc tgt cga gtg cac 11034

Asp Gly Pro Ile Tyr Asp Arg Leu Arg Ala Phe Cys Arg Val His

3665 3670 3675

cag acg aca act ttt gca gtg cta cta gca gct ttc cgc gca acg 11079

Gln Thr Thr Thr Phe Ala Val Leu Leu Ala Ala Phe Arg Ala Thr

3680 3685 3690

cac tat cgt ctt aca ggt gcc gaa gat gct act gtt ggc aca cca 11124

His Tyr Arg Leu Thr Gly Ala Glu Asp Ala Thr Val Gly Thr Pro

3695 3700 3705

atc gcc aac cgt aac cgg ccg gag ctt gaa aac ttg gtc gga ttc 11169

Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Leu Val Gly Phe

3710 3715 3720

ttc gtc aat act cag tgt atg aga att agt gtc gga gat gat gac 11214

Phe Val Asn Thr Gln Cys Met Arg Ile Ser Val Gly Asp Asp Asp

3725 3730 3735

acg ttt gag cag cta gtg cgc cag gtt cga tct aca gca acg gct 11259

Thr Phe Glu Gln Leu Val Arg Gln Val Arg Ser Thr Ala Thr Ala

3740 3745 3750

gca ttt gca aac caa gac gtt cct ttt gaa cgc atc gtg tca aca 11304

Ala Phe Ala Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Thr

3755 3760 3765

ctc ctg ccg ggc tct cgc gat acc gcc cgc aat cca ctg gta cag 11349

Leu Leu Pro Gly Ser Arg Asp Thr Ala Arg Asn Pro Leu Val Gln

3770 3775 3780

ctc atg ttt gct gtc cat tct ctc aag gac ctt ggc aaa att cag 11394

Leu Met Phe Ala Val His Ser Leu Lys Asp Leu Gly Lys Ile Gln

3785 3790 3795

ttc gag ggt ctc gtg ggc gag aca att ccc acg gct tct ttc act 11439

Phe Glu Gly Leu Val Gly Glu Thr Ile Pro Thr Ala Ser Phe Thr

3800 3805 3810

cga ttc gac gtc gag ttt cat ttg ttc cag gaa gtc ggt cgt ctt 11484

Arg Phe Asp Val Glu Phe His Leu Phe Gln Glu Val Gly Arg Leu

3815 3820 3825

agc gga aat gtg ctc ttc tcg act gat cta ttt gag ccg gag act 11529

Ser Gly Asn Val Leu Phe Ser Thr Asp Leu Phe Glu Pro Glu Thr

3830 3835 3840

atc cag ggc atg gtc tct gtg ttc atg gag atc ttg cgc gga gct 11574

Ile Gln Gly Met Val Ser Val Phe Met Glu Ile Leu Arg Gly Ala

3845 3850 3855

ctt gac cag cct cag atc ccc att gcc gtc cta ccg ctc aca gac 11619

Leu Asp Gln Pro Gln Ile Pro Ile Ala Val Leu Pro Leu Thr Asp

3860 3865 3870

ggc ctc acg gag ctt cgc aac aga ggc ctg ctt gaa gtt gag cag 11664

Gly Leu Thr Glu Leu Arg Asn Arg Gly Leu Leu Glu Val Glu Gln

3875 3880 3885

cct caa tat ccc cgc gac tcg agc gtc att gac gtg ttc cgc gct 11709

Pro Gln Tyr Pro Arg Asp Ser Ser Val Ile Asp Val Phe Arg Ala

3890 3895 3900

cag gtc gtt gct tgc cca gat gca atc gct gtg aaa gat tcg acg 11754

Gln Val Val Ala Cys Pro Asp Ala Ile Ala Val Lys Asp Ser Thr

3905 3910 3915

tcg cag ctc acc tat gcc caa ctt gat gag cag tcc gat gag gtg 11799

Ser Gln Leu Thr Tyr Ala Gln Leu Asp Glu Gln Ser Asp Glu Val

3920 3925 3930

gct gta tgg cta cat caa cga aag ttg cca gcg gaa tcc ctg gtt 11844

Ala Val Trp Leu His Gln Arg Lys Leu Pro Ala Glu Ser Leu Val

3935 3940 3945

gcc gtg cta gca cct aga tca tgc gag act atc att acc ttc ttc 11889

Ala Val Leu Ala Pro Arg Ser Cys Glu Thr Ile Ile Thr Phe Phe

3950 3955 3960

ggt att ttg aag gct aat cta gcc tat ctt cca ctc gat att aac 11934

Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Ile Asn

3965 3970 3975

gtc ccg gca gcc cgt att cag gca atc tta tcg tcc gtt gca ggg 11979

Val Pro Ala Ala Arg Ile Gln Ala Ile Leu Ser Ser Val Ala Gly

3980 3985 3990

aag aaa atc ctc cta ctt ggt tct gat cag gct cag ccg gaa att 12024

Lys Lys Ile Leu Leu Leu Gly Ser Asp Gln Ala Gln Pro Glu Ile

3995 4000 4005

cgg ctt gat gat gtt gaa ttt gta caa atc aat gaa acg att gac 12069

Arg Leu Asp Asp Val Glu Phe Val Gln Ile Asn Glu Thr Ile Asp

4010 4015 4020

cac aat atg gcg aag gat aat act acc cgc tct gga ccc tta gct 12114

His Asn Met Ala Lys Asp Asn Thr Thr Arg Ser Gly Pro Leu Ala

4025 4030 4035

aca agt ctt gct tat gtt atc ttc act tct gga tcc act ggc cag 12159

Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Gln

4040 4045 4050

ccg aag ggc gtc aag gtg gaa cac cgc ggt att gtt cgc ctc gtc 12204

Pro Lys Gly Val Lys Val Glu His Arg Gly Ile Val Arg Leu Val

4055 4060 4065

aag aat agc aac gtg gta gca aag atg cca gag gcg gca tgt gtt 12249

Lys Asn Ser Asn Val Val Ala Lys Met Pro Glu Ala Ala Cys Val

4070 4075 4080

gca cac ctt tca aat ctc gcg ttt gac gcc gcg aca tgg gaa atc 12294

Ala His Leu Ser Asn Leu Ala Phe Asp Ala Ala Thr Trp Glu Ile

4085 4090 4095

tac gct gca ctc ttg aat ggt ggc tcg ctc atc tgt atc gac tac 12339

Tyr Ala Ala Leu Leu Asn Gly Gly Ser Leu Ile Cys Ile Asp Tyr

4100 4105 4110

ttc acc acg cta gac agc aag gtc ctc gag gca gtt ttc gag cga 12384

Phe Thr Thr Leu Asp Ser Lys Val Leu Glu Ala Val Phe Glu Arg

4115 4120 4125

gaa caa atc cgt gca gcc atg ttc cca ccg gcg ctt ctg aaa caa 12429

Glu Gln Ile Arg Ala Ala Met Phe Pro Pro Ala Leu Leu Lys Gln

4130 4135 4140

tgc cta ctc aat atc ccc acg acc atc agc gcg cta gat gtt atc 12474

Cys Leu Leu Asn Ile Pro Thr Thr Ile Ser Ala Leu Asp Val Ile

4145 4150 4155

ctc gct gct ggt gac cga ttt gat agg cgc gac gct att gcg gcg 12519

Leu Ala Ala Gly Asp Arg Phe Asp Arg Arg Asp Ala Ile Ala Ala

4160 4165 4170

cag gcg ctt gtt gga ggt ggt gta tac aat gcc tac ggt cct acg 12564

Gln Ala Leu Val Gly Gly Gly Val Tyr Asn Ala Tyr Gly Pro Thr

4175 4180 4185

gaa aat act acg ctt agc aca ata tac aac gtt gtg gat ggc gat 12609

Glu Asn Thr Thr Leu Ser Thr Ile Tyr Asn Val Val Asp Gly Asp

4190 4195 4200

acc aac gtc aac ggt att cca atc ggg ctt cct gtc agc aac tct 12654

Thr Asn Val Asn Gly Ile Pro Ile Gly Leu Pro Val Ser Asn Ser

4205 4210 4215

ggc gtg tat gtc atg gat ccc aac cag cag ctt gtc ccg ttg ggc 12699

Gly Val Tyr Val Met Asp Pro Asn Gln Gln Leu Val Pro Leu Gly

4220 4225 4230

gtc atg gga gag ctt gtt gtg gtt ggc gat ggt gta gcc cga ggt 12744

Val Met Gly Glu Leu Val Val Val Gly Asp Gly Val Ala Arg Gly

4235 4240 4245

tac act gat cca gct ctt gat gtt gat cgt ttc atc aag gtt gaa 12789

Tyr Thr Asp Pro Ala Leu Asp Val Asp Arg Phe Ile Lys Val Glu

4250 4255 4260

atc gac ggc cag atc gta cga gcc tac cgc act ggt gac cgt gtt 12834

Ile Asp Gly Gln Ile Val Arg Ala Tyr Arg Thr Gly Asp Arg Val

4265 4270 4275

cga cac cga ccc aag gac ggt cag att gag ttc ttt ggc cga atg 12879

Arg His Arg Pro Lys Asp Gly Gln Ile Glu Phe Phe Gly Arg Met

4280 4285 4290

gat cag caa gtc aag att cga gga cat cgc att gaa ttg gct gag 12924

Asp Gln Gln Val Lys Ile Arg Gly His Arg Ile Glu Leu Ala Glu

4295 4300 4305

gta gag cac gtc atc ctc gat aac agc tta gtc cag gac gct gca 12969

Val Glu His Val Ile Leu Asp Asn Ser Leu Val Gln Asp Ala Ala

4310 4315 4320

gtc att gtc cac aag caa gct gac cag gag atc gaa atg atc gca 13014

Val Ile Val His Lys Gln Ala Asp Gln Glu Ile Glu Met Ile Ala

4325 4330 4335

ttt gct ata gtc cga ggc gat aac gac agc aag cac cca gag aag 13059

Phe Ala Ile Val Arg Gly Asp Asn Asp Ser Lys His Pro Glu Lys

4340 4345 4350

gat att cta gat cga gtg aag gct ttg ctt cca tca tac atg gtg 13104

Asp Ile Leu Asp Arg Val Lys Ala Leu Leu Pro Ser Tyr Met Val

4355 4360 4365

cca gct caa atg gtg ctg ctt aac agc atg cct ctc aat gcc aac 13149

Pro Ala Gln Met Val Leu Leu Asn Ser Met Pro Leu Asn Ala Asn

4370 4375 4380

ggc aag gtc gat cgc aaa gag ctt gct aag agg gcg ggg act gtg 13194

Gly Lys Val Asp Arg Lys Glu Leu Ala Lys Arg Ala Gly Thr Val

4385 4390 4395

ccg cga agc gag atg gca tac gtc gct cca gag agg gtt ccg cct 13239

Pro Arg Ser Glu Met Ala Tyr Val Ala Pro Glu Arg Val Pro Pro

4400 4405 4410

cgc aat gaa atc gaa aca att ctt tgc gaa gaa tac gcc gag gtc 13284

Arg Asn Glu Ile Glu Thr Ile Leu Cys Glu Glu Tyr Ala Glu Val

4415 4420 4425

ctt ggc gtc gag gtt ggt gtc atg gac aac ttt ttc gat ctt gga 13329

Leu Gly Val Glu Val Gly Val Met Asp Asn Phe Phe Asp Leu Gly

4430 4435 4440

ggg cac tct ctc atg gcg acc aag ctt gca gcc cgc gcc act cgt 13374

Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala Arg Ala Thr Arg

4445 4450 4455

cga ctt gat gca aag ttg tcc gtt aag gac att ttt gat tac cca 13419

Arg Leu Asp Ala Lys Leu Ser Val Lys Asp Ile Phe Asp Tyr Pro

4460 4465 4470

att tta gcc aac ctt gca gca gcg gtt caa cga ggc tcg act cca 13464

Ile Leu Ala Asn Leu Ala Ala Ala Val Gln Arg Gly Ser Thr Pro

4475 4480 4485

cat aat gcg att ctc gca acc aca tac tcc gga cca gtt gaa caa 13509

His Asn Ala Ile Leu Ala Thr Thr Tyr Ser Gly Pro Val Glu Gln

4490 4495 4500

tca ttc gcc cag ggg cgc ctg tgg ttc ttg gac cag ctg aat gtt 13554

Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp Gln Leu Asn Val

4505 4510 4515

ggc tcg aat tgg tac ctt cag cca att gcc ata cgc ata cgc gga 13599

Gly Ser Asn Trp Tyr Leu Gln Pro Ile Ala Ile Arg Ile Arg Gly

4520 4525 4530

tca ctc aat att aac gcg ctc act acc gcg ctt cat gcc cta gaa 13644

Ser Leu Asn Ile Asn Ala Leu Thr Thr Ala Leu His Ala Leu Glu

4535 4540 4545

caa cgt cac gag acg ttg cgc acc act ttt gag gaa gag gac ggc 13689

Gln Arg His Glu Thr Leu Arg Thr Thr Phe Glu Glu Glu Asp Gly

4550 4555 4560

gtt ggt atg cag gtc gtc caa gaa tat gac ccg ata gag ctc agg 13734

Val Gly Met Gln Val Val Gln Glu Tyr Asp Pro Ile Glu Leu Arg

4565 4570 4575

ata atg gat att gct gcc gat tat gac ggc gat tat aca gaa gcg 13779

Ile Met Asp Ile Ala Ala Asp Tyr Asp Gly Asp Tyr Thr Glu Ala

4580 4585 4590

ttg aag gga gag cag acg acc ccc ttc gat cta gag tcg gag cca 13824

Leu Lys Gly Glu Gln Thr Thr Pro Phe Asp Leu Glu Ser Glu Pro

4595 4600 4605

gga tgg agg gta tcg ctg ctc cgt atg aac gac aac gat cat atc 13869

Gly Trp Arg Val Ser Leu Leu Arg Met Asn Asp Asn Asp His Ile

4610 4615 4620

ttg tct ctg gtt cta cat cac atc atc tcc gat gga tgg tct gtc 13914

Leu Ser Leu Val Leu His His Ile Ile Ser Asp Gly Trp Ser Val

4625 4630 4635

gac gtt cta cgc cag gag ttg aag caa ttc tat gcc gct gca ctc 13959

Asp Val Leu Arg Gln Glu Leu Lys Gln Phe Tyr Ala Ala Ala Leu

4640 4645 4650

caa ggc ctg gat cct ctg tca ggg gct gat cca ctc ccc atc cag 14004

Gln Gly Leu Asp Pro Leu Ser Gly Ala Asp Pro Leu Pro Ile Gln

4655 4660 4665

tac cgc gac ttc tct ctc tgg caa aag cag cca gag caa gtt gct 14049

Tyr Arg Asp Phe Ser Leu Trp Gln Lys Gln Pro Glu Gln Val Ala

4670 4675 4680

gag cac gaa cga cag ctc aag tac tgg gtt gag cag ttg gct gac 14094

Glu His Glu Arg Gln Leu Lys Tyr Trp Val Glu Gln Leu Ala Asp

4685 4690 4695

aat tcc cct gct acg ctt ctt gcg gac cgg cca cgt cca tct gtg 14139

Asn Ser Pro Ala Thr Leu Leu Ala Asp Arg Pro Arg Pro Ser Val

4700 4705 4710

ctg tcg ggc caa gcc ggc tcg gtc ccg ctc tct atc gaa ggt cag 14184

Leu Ser Gly Gln Ala Gly Ser Val Pro Leu Ser Ile Glu Gly Gln

4715 4720 4725

gtc tat gag aaa ctt cag gcc ttc tgc cga gct cat caa acg acc 14229

Val Tyr Glu Lys Leu Gln Ala Phe Cys Arg Ala His Gln Thr Thr

4730 4735 4740

tcc ttt tcc gtt ttg ctc gct gcc ttc cga gct gct cac ttc cgc 14274

Ser Phe Ser Val Leu Leu Ala Ala Phe Arg Ala Ala His Phe Arg

4745 4750 4755

ctg acg ggt gtt gac gac gcg acg att ggc ata ccg atc gcc aat 14319

Leu Thr Gly Val Asp Asp Ala Thr Ile Gly Ile Pro Ile Ala Asn

4760 4765 4770

cgt aat cga cct gag cta gag cac ctg atc ggc ttt ttc gtt aac 14364

Arg Asn Arg Pro Glu Leu Glu His Leu Ile Gly Phe Phe Val Asn

4775 4780 4785

agg cag tgt atg cgg atc acg gtt ggg gaa gat gat acg ttc gaa 14409

Arg Gln Cys Met Arg Ile Thr Val Gly Glu Asp Asp Thr Phe Glu

4790 4795 4800

tct ctt atc cgc cag gtt cac tca aca gcc act gca gcg tat gct 14454

Ser Leu Ile Arg Gln Val His Ser Thr Ala Thr Ala Ala Tyr Ala

4805 4810 4815

aat caa gac gtg ccg ttc gag cga atc gta tcg tcc ctt ctt tct 14499

Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Ser Leu Leu Ser

4820 4825 4830

ggc tca aga gac aca tct cgt aat cca ctc gtc cag cta gta ttc 14544

Gly Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu Val Phe

4835 4840 4845

gcc gtt cac tcc cag aag aac ctt ggc aag ttt gag ttg caa gac 14589

Ala Val His Ser Gln Lys Asn Leu Gly Lys Phe Glu Leu Gln Asp

4850 4855 4860

ttg aca tct gag cca gtt gct gga gct atc tct act cga ttt gat 14634

Leu Thr Ser Glu Pro Val Ala Gly Ala Ile Ser Thr Arg Phe Asp

4865 4870 4875

gcg gaa ttt cat cta ttc cag gaa gaa gag agg ttg aac ggt gtt 14679

Ala Glu Phe His Leu Phe Gln Glu Glu Glu Arg Leu Asn Gly Val

4880 4885 4890

gtg tat tac gca acc gat ctg ttc gat gcg gag act atc caa ggg 14724

Val Tyr Tyr Ala Thr Asp Leu Phe Asp Ala Glu Thr Ile Gln Gly

4895 4900 4905

gtg gtg tct gtt ttc caa gaa atc tta cgt cgc ggc ctc aac cat 14769

Val Val Ser Val Phe Gln Glu Ile Leu Arg Arg Gly Leu Asn His

4910 4915 4920

cca cga acg ccg atc gca gct ctg tcg ctt acg gac ggg ctg gat 14814

Pro Arg Thr Pro Ile Ala Ala Leu Ser Leu Thr Asp Gly Leu Asp

4925 4930 4935

aat ctt cgc aag atg aat ctg gtt cac ttc aag cgg act gat tat 14859

Asn Leu Arg Lys Met Asn Leu Val His Phe Lys Arg Thr Asp Tyr

4940 4945 4950

ccc cgc gac tct agc atg gtc gac att ttc cgc gag caa gtc gct 14904

Pro Arg Asp Ser Ser Met Val Asp Ile Phe Arg Glu Gln Val Ala

4955 4960 4965

acc tat ccg gac gtg att gct gtc aag gac tcg act tta cag ctg 14949

Thr Tyr Pro Asp Val Ile Ala Val Lys Asp Ser Thr Leu Gln Leu

4970 4975 4980

acc tac gcg caa ctt gat caa caa tcc gat gag ata gcc acc tgg 14994

Thr Tyr Ala Gln Leu Asp Gln Gln Ser Asp Glu Ile Ala Thr Trp

4985 4990 4995

ttg cga aac aaa aaa atg gcg cca gaa act ctg gtg ggt gtc ctt 15039

Leu Arg Asn Lys Lys Met Ala Pro Glu Thr Leu Val Gly Val Leu

5000 5005 5010

gct ccg cga tcg tgc cag act atc gta gcc ttc ctt ggt gtc ctc 15084

Ala Pro Arg Ser Cys Gln Thr Ile Val Ala Phe Leu Gly Val Leu

5015 5020 5025

aag gcg aac cta gcc tat cta cct ctc gat gtc aat gcc ccg atg 15129

Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Ala Pro Met

5030 5035 5040

gcc cgc gtt gag aca atc atg tct tct gtg cca ggg agc aag ctg 15174

Ala Arg Val Glu Thr Ile Met Ser Ser Val Pro Gly Ser Lys Leu

5045 5050 5055

ctt ctt cta ggt tct gat gtg cct gcc cag gag atc cag ctg cag 15219

Leu Leu Leu Gly Ser Asp Val Pro Ala Gln Glu Ile Gln Leu Gln

5060 5065 5070

aat gtt gag ttg gtg cgt atc gaa gac acc ctc ggc cac gct gcc 15264

Asn Val Glu Leu Val Arg Ile Glu Asp Thr Leu Gly His Ala Ala

5075 5080 5085

tct gcc ggt aca gcg aca aca gaa ccc tct cca acc agc cta gcg 15309

Ser Ala Gly Thr Ala Thr Thr Glu Pro Ser Pro Thr Ser Leu Ala

5090 5095 5100

tac gtc ata ttc aca tct gga tcg acg ggt aag cca aag ggt gtg 15354

Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val

5105 5110 5115

atg gtc gag cat cga agc gtc att cgc ctc gtg aga aaa gaa agc 15399

Met Val Glu His Arg Ser Val Ile Arg Leu Val Arg Lys Glu Ser

5120 5125 5130

aat tcc atg tcc aag atg tct tcc aga gct cgg gtt gcg cac ttg 15444

Asn Ser Met Ser Lys Met Ser Ser Arg Ala Arg Val Ala His Leu

5135 5140 5145

act aac atc gcg ttc gac gtc tca gca tgg gag gta tat gct acg 15489

Thr Asn Ile Ala Phe Asp Val Ser Ala Trp Glu Val Tyr Ala Thr

5150 5155 5160

ctt ctc aac gga ggg act ctg gtc tgt gtc gat tat ttc act tcg 15534

Leu Leu Asn Gly Gly Thr Leu Val Cys Val Asp Tyr Phe Thr Ser

5165 5170 5175

ttc gat gct aaa gcc ctc ggt ctg ctg ttc gag cgg gag cag att 15579

Phe Asp Ala Lys Ala Leu Gly Leu Leu Phe Glu Arg Glu Gln Ile

5180 5185 5190

act gcg gct atg atc acg cct acg ttg ctc aaa cag tgc atc act 15624

Thr Ala Ala Met Ile Thr Pro Thr Leu Leu Lys Gln Cys Ile Thr

5195 5200 5205

att gta cca gaa gct ctc cgc aag ttg tcc gtt ctg tac acc ggt 15669

Ile Val Pro Glu Ala Leu Arg Lys Leu Ser Val Leu Tyr Thr Gly

5210 5215 5220

ggc gat cgc ttt gat agg cgc gat gct atc gcg aca aaa gcg ctt 15714

Gly Asp Arg Phe Asp Arg Arg Asp Ala Ile Ala Thr Lys Ala Leu

5225 5230 5235

gtc aag ggc cca gtt tac aat gca tgg ggc cct aca gaa acc aca 15759

Val Lys Gly Pro Val Tyr Asn Ala Trp Gly Pro Thr Glu Thr Thr

5240 5245 5250

atc gtc agc aca atc tat gag ctt gcc gat gac gat cag ttc acc 15804

Ile Val Ser Thr Ile Tyr Glu Leu Ala Asp Asp Asp Gln Phe Thr

5255 5260 5265

aat ggt gtg cct atc gga aag gct gtg agc aat tct tgg gcc tac 15849

Asn Gly Val Pro Ile Gly Lys Ala Val Ser Asn Ser Trp Ala Tyr

5270 5275 5280

gtc atg gat ctc aat caa caa ctc gtt cca gtt ggt gtc atg gga 15894

Val Met Asp Leu Asn Gln Gln Leu Val Pro Val Gly Val Met Gly

5285 5290 5295

gaa gct gtc gtt att gga gac ggc ctt gcc cga gga tat aca gat 15939

Glu Ala Val Val Ile Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp

5300 5305 5310

ccc gcc ctg gat tgc aac cgc ttt gtg cat atc act atc gat ggc 15984

Pro Ala Leu Asp Cys Asn Arg Phe Val His Ile Thr Ile Asp Gly

5315 5320 5325

aaa cgc gtg cgc gcc tat cga act ggt gac cgc gcg cgt tat cga 16029

Lys Arg Val Arg Ala Tyr Arg Thr Gly Asp Arg Ala Arg Tyr Arg

5330 5335 5340

cct aaa gat ggc gaa atc gaa ttc ttt ggg cgt atg gac cga cag 16074

Pro Lys Asp Gly Glu Ile Glu Phe Phe Gly Arg Met Asp Arg Gln

5345 5350 5355

ctc aag att cgt ggt cat cgt att gag ccc gcc gag att gag cat 16119

Leu Lys Ile Arg Gly His Arg Ile Glu Pro Ala Glu Ile Glu His

5360 5365 5370

gcc atg ctt ggc cac aat gac atc gtt gat gta gcc att gtc act 16164

Ala Met Leu Gly His Asn Asp Ile Val Asp Val Ala Ile Val Thr

5375 5380 5385

cgc cat caa gat ggt gca ggc tta gaa atg gtt gcc ttt gtt aca 16209

Arg His Gln Asp Gly Ala Gly Leu Glu Met Val Ala Phe Val Thr

5390 5395 5400

gcc cac act aac aag tct atc gaa cgc aat gaa gcc acc aat caa 16254

Ala His Thr Asn Lys Ser Ile Glu Arg Asn Glu Ala Thr Asn Gln

5405 5410 5415

gta gct gga tgg ggg gac cac ttc gaa tcg agt aca tat gca gag 16299

Val Ala Gly Trp Gly Asp His Phe Glu Ser Ser Thr Tyr Ala Glu

5420 5425 5430

ctc gac acc ctt gtc aag tct gat gtt ggc aag gac ttt gtc ggc 16344

Leu Asp Thr Leu Val Lys Ser Asp Val Gly Lys Asp Phe Val Gly

5435 5440 5445

tgg acg aac atg tat gat ggc ggc gcg atc gat cag gcc gag atg 16389

Trp Thr Asn Met Tyr Asp Gly Gly Ala Ile Asp Gln Ala Glu Met

5450 5455 5460

cag gaa tgg ctt gac gat acc ata cag acg att gtt gat ggt cag 16434

Gln Glu Trp Leu Asp Asp Thr Ile Gln Thr Ile Val Asp Gly Gln

5465 5470 5475

cct gct ggt cat gtc ttt gag atc ggt act ggt acc ggt atg atc 16479

Pro Ala Gly His Val Phe Glu Ile Gly Thr Gly Thr Gly Met Ile

5480 5485 5490

atg ttt ggt ctc ggg aaa cag gga ctg caa agc tac gtc ggc ctt 16524

Met Phe Gly Leu Gly Lys Gln Gly Leu Gln Ser Tyr Val Gly Leu

5495 5500 5505

gag ccc tca acc tcg gcc act acg tac gtc aac agg aag atc aag 16569

Glu Pro Ser Thr Ser Ala Thr Thr Tyr Val Asn Arg Lys Ile Lys

5510 5515 5520

acc gct cca acg gta gct ggc aaa gcc aag gta tat gtc ggc act 16614

Thr Ala Pro Thr Val Ala Gly Lys Ala Lys Val Tyr Val Gly Thr

5525 5530 5535

gca atg gag gcg gct caa ctc aat gga ctc cat ccg gaa gtt gtc 16659

Ala Met Glu Ala Ala Gln Leu Asn Gly Leu His Pro Glu Val Val

5540 5545 5550

gtc atc aac tct gtg gct caa tac ttc cct acg cca gaa tat ctc 16704

Val Ile Asn Ser Val Ala Gln Tyr Phe Pro Thr Pro Glu Tyr Leu

5555 5560 5565

ctc gag gtc gtc ggt att ctc act cag atg cca ggt gtc aaa cgc 16749

Leu Glu Val Val Gly Ile Leu Thr Gln Met Pro Gly Val Lys Arg

5570 5575 5580

ttg ttc ttt gga gac ata cga tcg tat gct act aac agg aaa ttc 16794

Leu Phe Phe Gly Asp Ile Arg Ser Tyr Ala Thr Asn Arg Lys Phe

5585 5590 5595

ctt gca gcc aga gcc ctt cat atg cta ggg tcc aac gcg aag aaa 16839

Leu Ala Ala Arg Ala Leu His Met Leu Gly Ser Asn Ala Lys Lys

5600 5605 5610

cat gac att cgc cgg aaa atg gct gag ttg gat gaa ttc gaa gaa 16884

His Asp Ile Arg Arg Lys Met Ala Glu Leu Asp Glu Phe Glu Glu

5615 5620 5625

gag ttg att gtc gat cct tct ttc ttc act ggt ctg gtc agc cga 16929

Glu Leu Ile Val Asp Pro Ser Phe Phe Thr Gly Leu Val Ser Arg

5630 5635 5640

ctg cca ggc cag gtc aag cat gtg gag att ctt cca aaa caa atg 16974

Leu Pro Gly Gln Val Lys His Val Glu Ile Leu Pro Lys Gln Met

5645 5650 5655

atc gcc aca aat gag ctc agc gcg tat cgt tat gca gcc gtt gtt 17019

Ile Ala Thr Asn Glu Leu Ser Ala Tyr Arg Tyr Ala Ala Val Val

5660 5665 5670

cat cta gct ctt ccc gaa gag cag cac ata gcg aaa atc gaa aag 17064

His Leu Ala Leu Pro Glu Glu Gln His Ile Ala Lys Ile Glu Lys

5675 5680 5685

ggc gcc tgg gtc gac ttc aca gcc acc aag atg gat cga agc gct 17109

Gly Ala Trp Val Asp Phe Thr Ala Thr Lys Met Asp Arg Ser Ala

5690 5695 5700

ctt gtt cat cat ctg cag agc tcg tca aac gct gaa att gta gct 17154

Leu Val His His Leu Gln Ser Ser Ser Asn Ala Glu Ile Val Ala

5705 5710 5715

atc agt aac att cca ttc agc aaa act aat ttc gat tgt cat ctt 17199

Ile Ser Asn Ile Pro Phe Ser Lys Thr Asn Phe Asp Cys His Leu

5720 5725 5730

ctc gca tct ctg gat gag gac gaa gaa cac tcg ctt gac gga tcc 17244

Leu Ala Ser Leu Asp Glu Asp Glu Glu His Ser Leu Asp Gly Ser

5735 5740 5745

gcc tgg atc aaa act att cat tcc agc gcc gaa cag tgt cca tcg 17289

Ala Trp Ile Lys Thr Ile His Ser Ser Ala Glu Gln Cys Pro Ser

5750 5755 5760

cta tcc gca acc gat ctc gtc gaa gtt gct aaa gag gtg ggc ttc 17334

Leu Ser Ala Thr Asp Leu Val Glu Val Ala Lys Glu Val Gly Phe

5765 5770 5775

cgt gtc gag ctc agc tgg gct cgg caa aag tct caa aac ggt gca 17379

Arg Val Glu Leu Ser Trp Ala Arg Gln Lys Ser Gln Asn Gly Ala

5780 5785 5790

ctt gac gct atc ttc cac caa tac caa tct ccc aaa gaa ggt agc 17424

Leu Asp Ala Ile Phe His Gln Tyr Gln Ser Pro Lys Glu Gly Ser

5795 5800 5805

cgt gtt cta ata cag ttc ccg act gac gac cag ggt cga tcg atg 17469

Arg Val Leu Ile Gln Phe Pro Thr Asp Asp Gln Gly Arg Ser Met

5810 5815 5820

gag tct ctt acg aac cga ccg tta cag cga gtt cag agc cgc cgg 17514

Glu Ser Leu Thr Asn Arg Pro Leu Gln Arg Val Gln Ser Arg Arg

5825 5830 5835

atc gaa aca cag att cgt gag cga cta cag gct gtg cta cca tca 17559

Ile Glu Thr Gln Ile Arg Glu Arg Leu Gln Ala Val Leu Pro Ser

5840 5845 5850

tac atg att cca gct cgg atc gtg gtg cta aat gag atg cca gtc 17604

Tyr Met Ile Pro Ala Arg Ile Val Val Leu Asn Glu Met Pro Val

5855 5860 5865

aat gcc aac ggc aaa gtc gac cgc aag gag ctg acg cgc aga gcg 17649

Asn Ala Asn Gly Lys Val Asp Arg Lys Glu Leu Thr Arg Arg Ala

5870 5875 5880

aag gtg gtc cca aga atc gaa aca gct gcg gag cgt att caa ccc 17694

Lys Val Val Pro Arg Ile Glu Thr Ala Ala Glu Arg Ile Gln Pro

5885 5890 5895

cga aat gaa gtc gaa gcg gtt ctg tgc gag gaa ttc agt gaa gtc 17739

Arg Asn Glu Val Glu Ala Val Leu Cys Glu Glu Phe Ser Glu Val

5900 5905 5910

ctc ggc gtc gaa gtt ggt gtc acg gac aac ttc ttc gat ctt ggt 17784

Leu Gly Val Glu Val Gly Val Thr Asp Asn Phe Phe Asp Leu Gly

5915 5920 5925

gga cac tcg ctc atg gct acg aag ctg gct gca cgt act ggg cgc 17829

Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala Arg Thr Gly Arg

5930 5935 5940

cga ctt gat gca aag gtg tct gtc aaa gac gtt ttc gac cac cca 17874

Arg Leu Asp Ala Lys Val Ser Val Lys Asp Val Phe Asp His Pro

5945 5950 5955

gta cta gcg gat ctt gcc gct gct att cag cga ggc tcg act ccc 17919

Val Leu Ala Asp Leu Ala Ala Ala Ile Gln Arg Gly Ser Thr Pro

5960 5965 5970

cac tcg gcg atc gtt act act gag tac tct gga cct gta gag cag 17964

His Ser Ala Ile Val Thr Thr Glu Tyr Ser Gly Pro Val Glu Gln

5975 5980 5985

tca tac gcc cag ggc cgc ctt tgg ttc ctt gaa caa ctc aat ttc 18009

Ser Tyr Ala Gln Gly Arg Leu Trp Phe Leu Glu Gln Leu Asn Phe

5990 5995 6000

aag gca acg tgg tat ctc cta ccg ctt gcg gtg cgg att cgt ggg 18054

Lys Ala Thr Trp Tyr Leu Leu Pro Leu Ala Val Arg Ile Arg Gly

6005 6010 6015

cca ctc aat atc aag gcc ctt acc acg gcg tta cat gcg cta gaa 18099

Pro Leu Asn Ile Lys Ala Leu Thr Thr Ala Leu His Ala Leu Glu

6020 6025 6030

cag cga cat gag act tta aga aca aca ttc att gag cgg gat ggt 18144

Gln Arg His Glu Thr Leu Arg Thr Thr Phe Ile Glu Arg Asp Gly

6035 6040 6045

gtg ggc aag cag gcc gtt cag cca ttt cag ccg aag gaa ctc gaa 18189

Val Gly Lys Gln Ala Val Gln Pro Phe Gln Pro Lys Glu Leu Glu

6050 6055 6060

atc gtc gac ata gcg gcc gac cac cag ggc gac tac ctt aaa gtg 18234

Ile Val Asp Ile Ala Ala Asp His Gln Gly Asp Tyr Leu Lys Val

6065 6070 6075

cta cgt gac gag cag act acc atg ttc aat cta gca act cag cct 18279

Leu Arg Asp Glu Gln Thr Thr Met Phe Asn Leu Ala Thr Gln Pro

6080 6085 6090

ggt tgg agg gtg act tta cac aga gtg gat caa aac acg cat aat 18324

Gly Trp Arg Val Thr Leu His Arg Val Asp Gln Asn Thr His Asn

6095 6100 6105

ctt tcc atc gtc atg cac cac atc att tca gac ggc tgg tca gtc 18369

Leu Ser Ile Val Met His His Ile Ile Ser Asp Gly Trp Ser Val

6110 6115 6120

gat gtt ctg cgc cac gag ctg agg cag ttc tat gct gct gcc ctc 18414

Asp Val Leu Arg His Glu Leu Arg Gln Phe Tyr Ala Ala Ala Leu

6125 6130 6135

cgg ggt cag gat ccc ctc gcg cat atc agc ccg ctc cca att caa 18459

Arg Gly Gln Asp Pro Leu Ala His Ile Ser Pro Leu Pro Ile Gln

6140 6145 6150

tac cgc gac ttc tcg ctc tgg caa aag cag cca gac cag atc atc 18504

Tyr Arg Asp Phe Ser Leu Trp Gln Lys Gln Pro Asp Gln Ile Ile

6155 6160 6165

gaa cat gca aaa caa ctt gag tac tgg acc aag caa ctg gca gac 18549

Glu His Ala Lys Gln Leu Glu Tyr Trp Thr Lys Gln Leu Ala Asp

6170 6175 6180

agc tcc cca gct gag ctc cca act gat tta ccc cgc ccg gcc gta 18594

Ser Ser Pro Ala Glu Leu Pro Thr Asp Leu Pro Arg Pro Ala Val

6185 6190 6195

ctg tca ggg aaa gct ggc gaa gtg gcc ctt tcc gtc aag ggc ccg 18639

Leu Ser Gly Lys Ala Gly Glu Val Ala Leu Ser Val Lys Gly Pro

6200 6205 6210

cta tat gag cgt ctg caa gct ttc tgc aag act cat cag aca act 18684

Leu Tyr Glu Arg Leu Gln Ala Phe Cys Lys Thr His Gln Thr Thr

6215 6220 6225

gcc ttc gcc aca ctc cta gca gcc ttc cgt gca aca cat cat cgc 18729

Ala Phe Ala Thr Leu Leu Ala Ala Phe Arg Ala Thr His His Arg

6230 6235 6240

ctt aca gga gcc gaa gac gct acc atc ggc aca cct atc gcc aac 18774

Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr Pro Ile Ala Asn

6245 6250 6255

cgc aac agg ccc gaa tta gag aac ctg att ggc ttc ttc gtg aat 18819

Arg Asn Arg Pro Glu Leu Glu Asn Leu Ile Gly Phe Phe Val Asn

6260 6265 6270

gct cag tgt atg cgc att act atc gat gga gac gag act ttc gag 18864

Ala Gln Cys Met Arg Ile Thr Ile Asp Gly Asp Glu Thr Phe Glu

6275 6280 6285

agt ctt ata cgt cag gtc cga gcc act gcg acg gct gcc atc gca 18909

Ser Leu Ile Arg Gln Val Arg Ala Thr Ala Thr Ala Ala Ile Ala

6290 6295 6300

aat caa gat gtc ccc ttt gaa cgt atc gtg tct acc atg caa tct 18954

Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Thr Met Gln Ser

6305 6310 6315

acc tca cga gac acg tca agg aat ccg ctt gta cag ctc atg ttc 18999

Thr Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu Met Phe

6320 6325 6330

gcc ctc cac tct caa cag gac ctc gga aaa atc caa cta gaa ggc 19044

Ala Leu His Ser Gln Gln Asp Leu Gly Lys Ile Gln Leu Glu Gly

6335 6340 6345

tgc gaa acg gag cct att ccc cga gct gta cgc act cgc ttc gat 19089

Cys Glu Thr Glu Pro Ile Pro Arg Ala Val Arg Thr Arg Phe Asp

6350 6355 6360

ctc gag ttc cat ctc tat caa gag caa ggg agc cta ggc ggc att 19134

Leu Glu Phe His Leu Tyr Gln Glu Gln Gly Ser Leu Gly Gly Ile

6365 6370 6375

gtg tac ttt gcc acc gat ttg ttc gag cct gag agc att gag ggg 19179

Val Tyr Phe Ala Thr Asp Leu Phe Glu Pro Glu Ser Ile Glu Gly

6380 6385 6390

atg gtt tcc att ttt aaa gaa atc ctc gct cga gct ctt gac caa 19224

Met Val Ser Ile Phe Lys Glu Ile Leu Ala Arg Ala Leu Asp Gln

6395 6400 6405

ccc caa acc cca ctg gcg ctt cta ccg ctc acc gat ggg ctg gct 19269

Pro Gln Thr Pro Leu Ala Leu Leu Pro Leu Thr Asp Gly Leu Ala

6410 6415 6420

gaa ctt cgc agg agg ggg ctg ctt gag att gaa agg ccc agc tat 19314

Glu Leu Arg Arg Arg Gly Leu Leu Glu Ile Glu Arg Pro Ser Tyr

6425 6430 6435

cct cgc gag tcg agc gtt gtt gac gtc ttc tgt agc cag gta gcg 19359

Pro Arg Glu Ser Ser Val Val Asp Val Phe Cys Ser Gln Val Ala

6440 6445 6450

gct tct ccc aac gca acc gct gtg aag gac tcg att tca cag ctc 19404

Ala Ser Pro Asn Ala Thr Ala Val Lys Asp Ser Ile Ser Gln Leu

6455 6460 6465

act tac gct cag cta aat gag caa tct gac aag gtc gct gct tgg 19449

Thr Tyr Ala Gln Leu Asn Glu Gln Ser Asp Lys Val Ala Ala Trp

6470 6475 6480

cta cac cag tgc aac ctt cca act gaa act ttg gtc gct gtg cta 19494

Leu His Gln Cys Asn Leu Pro Thr Glu Thr Leu Val Ala Val Leu

6485 6490 6495

gcg cct cga tct tgc caa aca gtt gtg gcc ttc ttg ggt att ctg 19539

Ala Pro Arg Ser Cys Gln Thr Val Val Ala Phe Leu Gly Ile Leu

6500 6505 6510

aag gcc aac cta gca tat ctt ccc cta gac gtc aat gtt ccg gca 19584

Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro Ala

6515 6520 6525

gct cgc att gag gca att ctc tca gaa gtc tct ggc cac ata ctt 19629

Ala Arg Ile Glu Ala Ile Leu Ser Glu Val Ser Gly His Ile Leu

6530 6535 6540

gtc tta ctt gga tct cat gtt tct gct ccc aag att gag ctc gct 19674

Val Leu Leu Gly Ser His Val Ser Ala Pro Lys Ile Glu Leu Ala

6545 6550 6555

gat gtc gaa ttc gtc aaa att gac aac aca gtc gag cac aat ttg 19719

Asp Val Glu Phe Val Lys Ile Asp Asn Thr Val Glu His Asn Leu

6560 6565 6570

ccg ggc cgc att gga tct gct cca tct gcc acg agc ctc gcc tat 19764

Pro Gly Arg Ile Gly Ser Ala Pro Ser Ala Thr Ser Leu Ala Tyr

6575 6580 6585

gtt att ttc aca tct gga tcg act ggc aag ccc aaa ggt gtt aag 19809

Val Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Lys

6590 6595 6600

gta gag cac cgc ggt att gtc cgc ctc gtt aaa gag agc aat gta 19854

Val Glu His Arg Gly Ile Val Arg Leu Val Lys Glu Ser Asn Val

6605 6610 6615

gta gca aaa atg cca caa gct gcg cgc att gct cac ttg tca aac 19899

Val Ala Lys Met Pro Gln Ala Ala Arg Ile Ala His Leu Ser Asn

6620 6625 6630

att gcc ttt gac gcg gct acg tgg gaa tta tat gct gcg ttg ctc 19944

Ile Ala Phe Asp Ala Ala Thr Trp Glu Leu Tyr Ala Ala Leu Leu

6635 6640 6645

aac ggc ggc acc ctc gtc tgt atc aac tat tta acc acg ctg gat 19989

Asn Gly Gly Thr Leu Val Cys Ile Asn Tyr Leu Thr Thr Leu Asp

6650 6655 6660

agt aaa gca ctc gag gcc gtg ttt gag cag gaa aag atc caa gcg 20034

Ser Lys Ala Leu Glu Ala Val Phe Glu Gln Glu Lys Ile Gln Ala

6665 6670 6675

gct atg ctt cca cca gca ctg ctc aaa cag tat ttg gtt aac att 20079

Ala Met Leu Pro Pro Ala Leu Leu Lys Gln Tyr Leu Val Asn Ile

6680 6685 6690

ccc gca gct atc ggt gca cta gaa gtg gtc ctt gtc gct ggt gac 20124

Pro Ala Ala Ile Gly Ala Leu Glu Val Val Leu Val Ala Gly Asp

6695 6700 6705

cgt ttc gat cga cgc gat gct gca gcc acg cag gct ctt gtt gga 20169

Arg Phe Asp Arg Arg Asp Ala Ala Ala Thr Gln Ala Leu Val Gly

6710 6715 6720

gca ggc gtg tat aac gcc tat gga ccg acg gag aat aca aca ctc 20214

Ala Gly Val Tyr Asn Ala Tyr Gly Pro Thr Glu Asn Thr Thr Leu

6725 6730 6735

agc act atc tac aat gtc gtt cag ggc gat gcc aat gtg aat ggc 20259

Ser Thr Ile Tyr Asn Val Val Gln Gly Asp Ala Asn Val Asn Gly

6740 6745 6750

gtc ccg att gga cgc cct gtc agc aac tct ggc gcc tac atc atg 20304

Val Pro Ile Gly Arg Pro Val Ser Asn Ser Gly Ala Tyr Ile Met

6755 6760 6765

aat atg aat cag gaa ctc gtt cct att ggc gtc ata ggc gag ctg 20349

Asn Met Asn Gln Glu Leu Val Pro Ile Gly Val Ile Gly Glu Leu

6770 6775 6780

gtc gta gta gga gac ggt gtc gcc cga gga tac acc gac cca gcc 20394

Val Val Val Gly Asp Gly Val Ala Arg Gly Tyr Thr Asp Pro Ala

6785 6790 6795

ttg gac gtc aac cgc ttc gtc aac gtc act att gaa ggc caa act 20439

Leu Asp Val Asn Arg Phe Val Asn Val Thr Ile Glu Gly Gln Thr

6800 6805 6810

atg agg gct tat agg act ggc gat cgt gcc cgc tat agg ccc aaa 20484

Met Arg Ala Tyr Arg Thr Gly Asp Arg Ala Arg Tyr Arg Pro Lys

6815 6820 6825

gac gca cag att gaa ttc ttt ggc cga atg gat caa cag atc aag 20529

Asp Ala Gln Ile Glu Phe Phe Gly Arg Met Asp Gln Gln Ile Lys

6830 6835 6840

att cga ggc cat cgt att gag cca gct gag gtc gag cat gcg ttg 20574

Ile Arg Gly His Arg Ile Glu Pro Ala Glu Val Glu His Ala Leu

6845 6850 6855

ctc aac aat gac ttg ctt cag gac gct gca gtc att atc cga aag 20619

Leu Asn Asn Asp Leu Leu Gln Asp Ala Ala Val Ile Ile Arg Lys

6860 6865 6870

caa caa aat gat gag ctg gag atg gtt gct ttt gta gaa gca aac 20664

Gln Gln Asn Asp Glu Leu Glu Met Val Ala Phe Val Glu Ala Asn

6875 6880 6885

agc aat aag tcg atc gaa caa gag gcg agc aac caa gta gaa gac 20709

Ser Asn Lys Ser Ile Glu Gln Glu Ala Ser Asn Gln Val Glu Asp

6890 6895 6900

tgg ggc gct caa ttc gag agc aac gtc tac gcc gag atc gag gca 20754

Trp Gly Ala Gln Phe Glu Ser Asn Val Tyr Ala Glu Ile Glu Ala

6905 6910 6915

atc gat gcc tct gct gtt ggt aac gac ttc atg ggt tgg act tcc 20799

Ile Asp Ala Ser Ala Val Gly Asn Asp Phe Met Gly Trp Thr Ser

6920 6925 6930

atg tac gac ggc agc gcg atc gac aag gct gag atg cag gaa tgg 20844

Met Tyr Asp Gly Ser Ala Ile Asp Lys Ala Glu Met Gln Glu Trp

6935 6940 6945

ctc gat gat act atg cag aca ata ctt gat ggt cga cca gcc ggc 20889

Leu Asp Asp Thr Met Gln Thr Ile Leu Asp Gly Arg Pro Ala Gly

6950 6955 6960

cgc gtt ctc gaa atc ggc act ggc acg ggt atg atc ctc ttc aat 20934

Arg Val Leu Glu Ile Gly Thr Gly Thr Gly Met Ile Leu Phe Asn

6965 6970 6975

ctt ggt gaa ggg tta cag agc tat gtc ggt ctc gaa cca tct acc 20979

Leu Gly Glu Gly Leu Gln Ser Tyr Val Gly Leu Glu Pro Ser Thr

6980 6985 6990

tcg gcg gct gcg ttc gtc aat cgc agg att cag aca ctt cca gct 21024

Ser Ala Ala Ala Phe Val Asn Arg Arg Ile Gln Thr Leu Pro Ala

6995 7000 7005

ttc gct ggt aaa gct gaa gtt cac gtg ggt aca gcg aca gat ata 21069

Phe Ala Gly Lys Ala Glu Val His Val Gly Thr Ala Thr Asp Ile

7010 7015 7020

agc caa ctt caa gat ctc cgc ccg gaa gta gtg gtt atc aac tcg 21114

Ser Gln Leu Gln Asp Leu Arg Pro Glu Val Val Val Ile Asn Ser

7025 7030 7035

gtg gct cag tac ttc cca tcg cct gag tac ttg tct aag gtt ttg 21159

Val Ala Gln Tyr Phe Pro Ser Pro Glu Tyr Leu Ser Lys Val Leu

7040 7045 7050

tac gca cta gcc caa att cct ggc gtc aag cgt ttg ttc ttt gga 21204

Tyr Ala Leu Ala Gln Ile Pro Gly Val Lys Arg Leu Phe Phe Gly

7055 7060 7065

gac atg cga tct tac gcc atc aac gac cag ttc ctt gca gct cgc 21249

Asp Met Arg Ser Tyr Ala Ile Asn Asp Gln Phe Leu Ala Ala Arg

7070 7075 7080

gcc tta cac aac ata ggt agc aag gct act aag agc gcc att cga 21294

Ala Leu His Asn Ile Gly Ser Lys Ala Thr Lys Ser Ala Ile Arg

7085 7090 7095

agc aag atg gtc gat ctg gaa aac tct gag gaa gaa ttg ctc gtc 21339

Ser Lys Met Val Asp Leu Glu Asn Ser Glu Glu Glu Leu Leu Val

7100 7105 7110

gac cca acc ttc ttc acc aac cta gcg acc gag ctt cca gag gtt 21384

Asp Pro Thr Phe Phe Thr Asn Leu Ala Thr Glu Leu Pro Glu Val

7115 7120 7125

gag cat gtt gag att ctg cca aaa cgc atg cag gct acc aac gaa 21429

Glu His Val Glu Ile Leu Pro Lys Arg Met Gln Ala Thr Asn Glu

7130 7135 7140

ctt agc gca tac cga tac gct gcg gtt gtt cat att cga gac cca 21474

Leu Ser Ala Tyr Arg Tyr Ala Ala Val Val His Ile Arg Asp Pro

7145 7150 7155

gca agg cag gcg cag aca gtg cac acc att gat cct acc gct tgg 21519

Ala Arg Gln Ala Gln Thr Val His Thr Ile Asp Pro Thr Ala Trp

7160 7165 7170

atc gat ttt agc gca tct caa atg aat cgt act gct ctt gcc aac 21564

Ile Asp Phe Ser Ala Ser Gln Met Asn Arg Thr Ala Leu Ala Asn

7175 7180 7185

ctc ttg caa aac tca gca gat gct gca gct atc gct gtc agc aac 21609

Leu Leu Gln Asn Ser Ala Asp Ala Ala Ala Ile Ala Val Ser Asn

7190 7195 7200

atc ccg tac agc aag acg atc ttg gcg cgc cac att gtt cag tcg 21654

Ile Pro Tyr Ser Lys Thr Ile Leu Ala Arg His Ile Val Gln Ser

7205 7210 7215

ctt gat gac gat ctc aca gac agc gat gat cca caa gat gag ctt 21699

Leu Asp Asp Asp Leu Thr Asp Ser Asp Asp Pro Gln Asp Glu Leu

7220 7225 7230

gaa gga gct gct tgg atg tct gct atc cgg tcc aat atc aaa acc 21744

Glu Gly Ala Ala Trp Met Ser Ala Ile Arg Ser Asn Ile Lys Thr

7235 7240 7245

tgt gca tcg ctg tcc gcc ttc gac ctt gcg caa ctt gcc cag gag 21789

Cys Ala Ser Leu Ser Ala Phe Asp Leu Ala Gln Leu Ala Gln Glu

7250 7255 7260

aaa ggc ttc cgt gtg gag ctt agt tgg gca aga caa cga acc cat 21834

Lys Gly Phe Arg Val Glu Leu Ser Trp Ala Arg Gln Arg Thr His

7265 7270 7275

cat gga gct tta gac gct gtt ttc cat cat tac aag tct aac cag 21879

His Gly Ala Leu Asp Ala Val Phe His His Tyr Lys Ser Asn Gln

7280 7285 7290

gat ggt ggt cgt gtc ctg gtg cag ttc ccg act gat agt cga cct 21924

Asp Gly Gly Arg Val Leu Val Gln Phe Pro Thr Asp Ser Arg Pro

7295 7300 7305

cgt cta tca gga caa ctc aca aac caa ccg ctg cag cgg cta cag 21969

Arg Leu Ser Gly Gln Leu Thr Asn Gln Pro Leu Gln Arg Leu Gln

7310 7315 7320

agt cga cga ttg gag gca cag att cga gat cag ctc agc gct tta 22014

Ser Arg Arg Leu Glu Ala Gln Ile Arg Asp Gln Leu Ser Ala Leu

7325 7330 7335

ctt cca tct tac atg atc ccg tcg ctt atc gtg atg gtc gat gag 22059

Leu Pro Ser Tyr Met Ile Pro Ser Leu Ile Val Met Val Asp Glu

7340 7345 7350

atg ccc ttg aat gcc aat ggc aag gta gac agg aaa gcc cta gag 22104

Met Pro Leu Asn Ala Asn Gly Lys Val Asp Arg Lys Ala Leu Glu

7355 7360 7365

cga agg gct cgc atg gtt cag aaa gtt gaa aag cca gct tct gag 22149

Arg Arg Ala Arg Met Val Gln Lys Val Glu Lys Pro Ala Ser Glu

7370 7375 7380

cga gtc ggt gca cgt aac gag atc gaa gcc gcg ctg tgc gaa gta 22194

Arg Val Gly Ala Arg Asn Glu Ile Glu Ala Ala Leu Cys Glu Val

7385 7390 7395

ttc gta gat cta ctc ggc act gag gtc agc att act gac aac ttc 22239

Phe Val Asp Leu Leu Gly Thr Glu Val Ser Ile Thr Asp Asn Phe

7400 7405 7410

ttt aat ctt ggc ggt cat tcg ctc atg gcc aca aaa ttg gct gct 22284

Phe Asn Leu Gly Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala

7415 7420 7425

cga att agc aga cgc ctt gac gca cgc atc tct gtc aag gat gtg 22329

Arg Ile Ser Arg Arg Leu Asp Ala Arg Ile Ser Val Lys Asp Val

7430 7435 7440

ttt gac tac cct gtt ctc gcc gac ctt gcg ggc gcc gtt cag cga 22374

Phe Asp Tyr Pro Val Leu Ala Asp Leu Ala Gly Ala Val Gln Arg

7445 7450 7455

ggc tca act cca cac aac cca atc gtc gcg acg ccc tac tca ggg 22419

Gly Ser Thr Pro His Asn Pro Ile Val Ala Thr Pro Tyr Ser Gly

7460 7465 7470

ccc gtc gag cag tcc ttt gct cag ggc cgc ctg tgg ttc ttg gac 22464

Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp

7475 7480 7485

cag ctt aac gcc ggt tcg ctg tgg tac atc cag cca atc gcc gta 22509

Gln Leu Asn Ala Gly Ser Leu Trp Tyr Ile Gln Pro Ile Ala Val

7490 7495 7500

cgc gta cgc ggt tcg ctc aat att ggt gcg ctg act aca gca ctc 22554

Arg Val Arg Gly Ser Leu Asn Ile Gly Ala Leu Thr Thr Ala Leu

7505 7510 7515

aat gcg ctt gag aag cgc cac gaa ccg ttg cgc acg act ttc gaa 22599

Asn Ala Leu Glu Lys Arg His Glu Pro Leu Arg Thr Thr Phe Glu

7520 7525 7530

gag cat gac ggc att ggt gtg caa gtc gtt caa ccg cat cag ccg 22644

Glu His Asp Gly Ile Gly Val Gln Val Val Gln Pro His Gln Pro

7535 7540 7545

aag aag ctt aga att gtc gat acg gtg gct aac tat cag ggt gac 22689

Lys Lys Leu Arg Ile Val Asp Thr Val Ala Asn Tyr Gln Gly Asp

7550 7555 7560

ttc atc agg gct cta cgg aag gag cag cag act cta ttc aat ctc 22734

Phe Ile Arg Ala Leu Arg Lys Glu Gln Gln Thr Leu Phe Asn Leu

7565 7570 7575

gcg acc gag cca ggc tgg aga gtg tct ctg cta cgc att ggg gag 22779

Ala Thr Glu Pro Gly Trp Arg Val Ser Leu Leu Arg Ile Gly Glu

7580 7585 7590

gac gac aac att ctc tcc atc gtc atg cac cac atc att tca gac 22824

Asp Asp Asn Ile Leu Ser Ile Val Met His His Ile Ile Ser Asp

7595 7600 7605

ggt tgg tct gtt gac atc ttg cgt caa gat cta aaa cta ttc tat 22869

Gly Trp Ser Val Asp Ile Leu Arg Gln Asp Leu Lys Leu Phe Tyr

7610 7615 7620

gcc gcc gct ctc aaa agc cag gag ccg caa gta gac gcg ctc cca 22914

Ala Ala Ala Leu Lys Ser Gln Glu Pro Gln Val Asp Ala Leu Pro

7625 7630 7635

atc caa tat cgt gac ttt gcc ttc tgg cag aaa cag ccg gag cag 22959

Ile Gln Tyr Arg Asp Phe Ala Phe Trp Gln Lys Gln Pro Glu Gln

7640 7645 7650

gta gct gag cac cag cga caa ctc gac tac tgg att gaa caa ttg 23004

Val Ala Glu His Gln Arg Gln Leu Asp Tyr Trp Ile Glu Gln Leu

7655 7660 7665

aaa gac agc aag cct gct gag ctt atc acc gat ttt ccg cgg cca 23049

Lys Asp Ser Lys Pro Ala Glu Leu Ile Thr Asp Phe Pro Arg Pro

7670 7675 7680

gag gtg ctg tct ggc act gct ggc atc gta cag ctt gcc gtg gac 23094

Glu Val Leu Ser Gly Thr Ala Gly Ile Val Gln Leu Ala Val Asp

7685 7690 7695

ggc caa gtc tac gag ggt ctc cgg gct ttc tgc aga att cat caa 23139

Gly Gln Val Tyr Glu Gly Leu Arg Ala Phe Cys Arg Ile His Gln

7700 7705 7710

aca acg tcc ttc gtg gta ctt ctt gca gcc ttt aga gct gcc cat 23184

Thr Thr Ser Phe Val Val Leu Leu Ala Ala Phe Arg Ala Ala His

7715 7720 7725

tac cgt cta aca ggc acc gag gac gcg aca atc ggt tct ccc atc 23229

Tyr Arg Leu Thr Gly Thr Glu Asp Ala Thr Ile Gly Ser Pro Ile

7730 7735 7740

gcc aac cgg aat cgg ccc gaa ctg gag agc ctc att ggc ttc ttc 23274

Ala Asn Arg Asn Arg Pro Glu Leu Glu Ser Leu Ile Gly Phe Phe

7745 7750 7755

gtc aat acc caa tgt atg cgc att atg gtc gga gag gac gac aca 23319

Val Asn Thr Gln Cys Met Arg Ile Met Val Gly Glu Asp Asp Thr

7760 7765 7770

ttc gaa cga ttg gta cag cag gtc cga tca acg aca aca gct gca 23364

Phe Glu Arg Leu Val Gln Gln Val Arg Ser Thr Thr Thr Ala Ala

7775 7780 7785

ttt gct aac cag gac gtt ccc ttc gaa cga atc gtt tca tcc gtc 23409

Phe Ala Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Ser Val

7790 7795 7800

cag tca acc tca aga gat gcc tcc cga aac cct ttg gta cag ctc 23454

Gln Ser Thr Ser Arg Asp Ala Ser Arg Asn Pro Leu Val Gln Leu

7805 7810 7815

atg ttt gca ctt cat tca cag cag ggt atc ggc ctg atg gaa ctc 23499

Met Phe Ala Leu His Ser Gln Gln Gly Ile Gly Leu Met Glu Leu

7820 7825 7830

gaa ggt gtt gag aca gag cca att gca aga gat gta tcg acg cgc 23544

Glu Gly Val Glu Thr Glu Pro Ile Ala Arg Asp Val Ser Thr Arg

7835 7840 7845

ttc gac atc gag ttc cat ctt tac cag aag gaa gag agc tta cac 23589

Phe Asp Ile Glu Phe His Leu Tyr Gln Lys Glu Glu Ser Leu His

7850 7855 7860

ggt gtt gtc cac ttt gct gcc gac ttg ttc gag cct gag act att 23634

Gly Val Val His Phe Ala Ala Asp Leu Phe Glu Pro Glu Thr Ile

7865 7870 7875

caa ggc ttg gtc tcc gtc ttc cag gaa att ctt cgc cga gga ctc 23679

Gln Gly Leu Val Ser Val Phe Gln Glu Ile Leu Arg Arg Gly Leu

7880 7885 7890

gag aca cct cga ttg cca atc agc att ctg cct ctt gat aac aac 23724

Glu Thr Pro Arg Leu Pro Ile Ser Ile Leu Pro Leu Asp Asn Asn

7895 7900 7905

att ccg gag ctt ctc gtc ggt atg ctc gat gtc gac act cca gag 23769

Ile Pro Glu Leu Leu Val Gly Met Leu Asp Val Asp Thr Pro Glu

7910 7915 7920

tat cct cgc gat tca agc gtg gtt gat gtg ttc cgc acc caa gtt 23814

Tyr Pro Arg Asp Ser Ser Val Val Asp Val Phe Arg Thr Gln Val

7925 7930 7935

gct gcc agc ccg gat gcg atc gcc gtt aaa gat tca act tcg cag 23859

Ala Ala Ser Pro Asp Ala Ile Ala Val Lys Asp Ser Thr Ser Gln

7940 7945 7950

ctc acc tac gct cag ctt gat gaa gaa tcc aac aaa gtg gct aca 23904

Leu Thr Tyr Ala Gln Leu Asp Glu Glu Ser Asn Lys Val Ala Thr

7955 7960 7965

tgg ttg agt caa agg cag ctg gct ccc gaa acg ctg gta ggc gtc 23949

Trp Leu Ser Gln Arg Gln Leu Ala Pro Glu Thr Leu Val Gly Val

7970 7975 7980

ctt gcg cct aga tcg tgc cca aca atc gtt aca ttc ttt ggt atc 23994

Leu Ala Pro Arg Ser Cys Pro Thr Ile Val Thr Phe Phe Gly Ile

7985 7990 7995

ctc aag gcc agt ctg gcg tat ctc ccg cta gac gtc aac gta cca 24039

Leu Lys Ala Ser Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro

8000 8005 8010

tct gct cgt atc gag gcg atc ctc tcg gca gtc cct gac cat aag 24084

Ser Ala Arg Ile Glu Ala Ile Leu Ser Ala Val Pro Asp His Lys

8015 8020 8025

ttg gtc ttc ctt ggt gct gac gtc ccc gat cca gag gct cca ctt 24129

Leu Val Phe Leu Gly Ala Asp Val Pro Asp Pro Glu Ala Pro Leu

8030 8035 8040

gtc aac gtg gag ctg gtg cgg atc gac gac atc tta cgc caa agc 24174

Val Asn Val Glu Leu Val Arg Ile Asp Asp Ile Leu Arg Gln Ser

8045 8050 8055

att cac gct tcg aat gca ggg ctt cta gca aat cac ccc tta gca 24219

Ile His Ala Ser Asn Ala Gly Leu Leu Ala Asn His Pro Leu Ala

8060 8065 8070

act agt ctt gcc tac gtc atg ttt aca tct gga tct aca ggc aag 24264

Thr Ser Leu Ala Tyr Val Met Phe Thr Ser Gly Ser Thr Gly Lys

8075 8080 8085

cct aag ggt gtc atg gtt gag cat cga agt att gta cgc ttg gta 24309

Pro Lys Gly Val Met Val Glu His Arg Ser Ile Val Arg Leu Val

8090 8095 8100

aag gaa acg aac cta gtc cca gca gta gag gca gtt tcc tca gta 24354

Lys Glu Thr Asn Leu Val Pro Ala Val Glu Ala Val Ser Ser Val

8105 8110 8115

gct cac atc tct aat gtt gct ttc gat gct gca act tgg gag ata 24399

Ala His Ile Ser Asn Val Ala Phe Asp Ala Ala Thr Trp Glu Ile

8120 8125 8130

tac gct gcg ctc cta aat ggc gga act act gtt tgc att gat cac 24444

Tyr Ala Ala Leu Leu Asn Gly Gly Thr Thr Val Cys Ile Asp His

8135 8140 8145

att act gtg ttg gat cct gct aaa cta gct ctc gtc ttc tca agc 24489

Ile Thr Val Leu Asp Pro Ala Lys Leu Ala Leu Val Phe Ser Ser

8150 8155 8160

gag aag atc aaa gct gcg ttc ttc tca act gct ttg ctc aag cag 24534

Glu Lys Ile Lys Ala Ala Phe Phe Ser Thr Ala Leu Leu Lys Gln

8165 8170 8175

cgg ctc tac gaa gag cca tct act atc act gga ctc gat ctt tta 24579

Arg Leu Tyr Glu Glu Pro Ser Thr Ile Thr Gly Leu Asp Leu Leu

8180 8185 8190

tat gct ggc ggt gag aga atg agg cct caa gac gct ctt aag acg 24624

Tyr Ala Gly Gly Glu Arg Met Arg Pro Gln Asp Ala Leu Lys Thr

8195 8200 8205

cga gaa cta gtt cgt ggt agc ttc tgc cac gtc tat ggg ccg aca 24669

Arg Glu Leu Val Arg Gly Ser Phe Cys His Val Tyr Gly Pro Thr

8210 8215 8220

gaa aat aca aca ttc agc act gtc tat cct atg ggg gta gaa gaa 24714

Glu Asn Thr Thr Phe Ser Thr Val Tyr Pro Met Gly Val Glu Glu

8225 8230 8235

cgc tgc gtc aac gga cta cct atc ggc cgc gca gtc agc cat tca 24759

Arg Cys Val Asn Gly Leu Pro Ile Gly Arg Ala Val Ser His Ser

8240 8245 8250

ggc gca gtg atc atg gat gcc aat cag cgc ctc gtg ccg tta ggg 24804

Gly Ala Val Ile Met Asp Ala Asn Gln Arg Leu Val Pro Leu Gly

8255 8260 8265

gtg atg ggc gaa ctt gtt gtc aca ggt gat ggt ctc gcc cga gga 24849

Val Met Gly Glu Leu Val Val Thr Gly Asp Gly Leu Ala Arg Gly

8270 8275 8280

tac acc gat ccc gct ctg aat cgt gat cgc ttc gtg gaa gtc aat 24894

Tyr Thr Asp Pro Ala Leu Asn Arg Asp Arg Phe Val Glu Val Asn

8285 8290 8295

atc cac ggt cag gtc ctg agg gca tat cgc aca ggc gac caa gcc 24939

Ile His Gly Gln Val Leu Arg Ala Tyr Arg Thr Gly Asp Gln Ala

8300 8305 8310

cgc tat cga ccc aaa gat ggc cag att gag ttc tcc ggg cgt atg 24984

Arg Tyr Arg Pro Lys Asp Gly Gln Ile Glu Phe Ser Gly Arg Met

8315 8320 8325

gac aga cag ctg aaa att cga ggc cat cgt atc gag cca gct gag 25029

Asp Arg Gln Leu Lys Ile Arg Gly His Arg Ile Glu Pro Ala Glu

8330 8335 8340

gtc gag cac gcc ata ctt agc cac gac gat atc cga aac gca gtt 25074

Val Glu His Ala Ile Leu Ser His Asp Asp Ile Arg Asn Ala Val

8345 8350 8355

gtg gtt act cga caa cag gaa ggc caa gat ctg gaa atg gtc gct 25119

Val Val Thr Arg Gln Gln Glu Gly Gln Asp Leu Glu Met Val Ala

8360 8365 8370

ttc gtc tct act ccc aac gat caa acc gta gaa cgc gac gaa gct 25164

Phe Val Ser Thr Pro Asn Asp Gln Thr Val Glu Arg Asp Glu Ala

8375 8380 8385

agg aat caa gtt gag gac tgg ggg gct caa ttc gag agc aac gtt 25209

Arg Asn Gln Val Glu Asp Trp Gly Ala Gln Phe Glu Ser Asn Val

8390 8395 8400

tac gcc gag atc gag gag atc gac tcc tct gcc gtt ggg aat gac 25254

Tyr Ala Glu Ile Glu Glu Ile Asp Ser Ser Ala Val Gly Asn Asp

8405 8410 8415

ttc atg ggc tgg acg tct atg tac gac ggt act gcg atc gat aaa 25299

Phe Met Gly Trp Thr Ser Met Tyr Asp Gly Thr Ala Ile Asp Lys

8420 8425 8430

gca gag atg cag gag tgg ctc gac gat act atg aga acc ctc cat 25344

Ala Glu Met Gln Glu Trp Leu Asp Asp Thr Met Arg Thr Leu His

8435 8440 8445

gac ggc cga gat cct ggc cac gtc ctc gaa gtt ggt aca ggc acg 25389

Asp Gly Arg Asp Pro Gly His Val Leu Glu Val Gly Thr Gly Thr

8450 8455 8460

ggc atg atc cta ttc aat ctc ggc aag ggc ctg cag agc tac gtc 25434

Gly Met Ile Leu Phe Asn Leu Gly Lys Gly Leu Gln Ser Tyr Val

8465 8470 8475

ggc ctc gag ccg tcg act tcg gca gct gca ttc gtc aat cgc aag 25479

Gly Leu Glu Pro Ser Thr Ser Ala Ala Ala Phe Val Asn Arg Lys

8480 8485 8490

att gag act atc tca tca ttg gcg ggt aag gct aaa gtt gag att 25524

Ile Glu Thr Ile Ser Ser Leu Ala Gly Lys Ala Lys Val Glu Ile

8495 8500 8505

ggc aca gca acc gac gta ggc cag ctc aag aac ctc cgc tcc gat 25569

Gly Thr Ala Thr Asp Val Gly Gln Leu Lys Asn Leu Arg Ser Asp

8510 8515 8520

ttg gtc gtt att aat tcg gta gct caa tac ttc cct tcc ccc gag 25614

Leu Val Val Ile Asn Ser Val Ala Gln Tyr Phe Pro Ser Pro Glu

8525 8530 8535

tat cta gtc gaa gca gta act gct cta gtc cac atc cca ggt gta 25659

Tyr Leu Val Glu Ala Val Thr Ala Leu Val His Ile Pro Gly Val

8540 8545 8550

aaa cgc ttg ttc ttc ggc gac atg cga tcc tac gcc atg aat aag 25704

Lys Arg Leu Phe Phe Gly Asp Met Arg Ser Tyr Ala Met Asn Lys

8555 8560 8565

cag ttc ctg gtt gct agg gct ctc cgt acg cta gga gcc aag gca 25749

Gln Phe Leu Val Ala Arg Ala Leu Arg Thr Leu Gly Ala Lys Ala

8570 8575 8580

aac aag gac gat gtt cgc agg aag atg gtg gag cta gag gaa ttc 25794

Asn Lys Asp Asp Val Arg Arg Lys Met Val Glu Leu Glu Glu Phe

8585 8590 8595

gaa gag gaa cta ctc gtg gat cca gcc ttc ttc aca ggc ctc gca 25839

Glu Glu Glu Leu Leu Val Asp Pro Ala Phe Phe Thr Gly Leu Ala

8600 8605 8610

aac tgg ctg tca gaa gtc gaa cat gtc gag att cta ccc aaa cag 25884

Asn Trp Leu Ser Glu Val Glu His Val Glu Ile Leu Pro Lys Gln

8615 8620 8625

atg aca tct acc aac gag ctg agc tca tac cgt tat gca gcc atc 25929

Met Thr Ser Thr Asn Glu Leu Ser Ser Tyr Arg Tyr Ala Ala Ile

8630 8635 8640

gta cac cta cgg ctt cca ggc cag gag gca caa cca gtc gtg aca 25974

Val His Leu Arg Leu Pro Gly Gln Glu Ala Gln Pro Val Val Thr

8645 8650 8655

gtc aat caa gac gcc tgg gtt gac ttc gga gga tcc aag atg gat 26019

Val Asn Gln Asp Ala Trp Val Asp Phe Gly Gly Ser Lys Met Asp

8660 8665 8670

cga cac gct ctt ctt cac cac cta caa agc tca cca aag gcc gaa 26064

Arg His Ala Leu Leu His His Leu Gln Ser Ser Pro Lys Ala Glu

8675 8680 8685

act gta gcc atc agc aac atc ccc tat agc aag acg att tat gag 26109

Thr Val Ala Ile Ser Asn Ile Pro Tyr Ser Lys Thr Ile Tyr Glu

8690 8695 8700

cgc cat gtc ctc gca tct ttg gat gac gat gaa gtc gag gac tcg 26154

Arg His Val Leu Ala Ser Leu Asp Asp Asp Glu Val Glu Asp Ser

8705 8710 8715

tta gat ggg tca gca tgg cta tcg gct gtt cgc tct acc gcc gaa 26199

Leu Asp Gly Ser Ala Trp Leu Ser Ala Val Arg Ser Thr Ala Glu

8720 8725 8730

cag tgc gcg tca ctc tcc gga gtc gac tta gtt caa atc gcc aag 26244

Gln Cys Ala Ser Leu Ser Gly Val Asp Leu Val Gln Ile Ala Lys

8735 8740 8745

gag gcc ggc ttc cgc gtg gag ctc agc tgg gcg cga cag agg tct 26289

Glu Ala Gly Phe Arg Val Glu Leu Ser Trp Ala Arg Gln Arg Ser

8750 8755 8760

cag aag ggt gga atc gac gcg gtc ttc cac cac tac gag tca gtg 26334

Gln Lys Gly Gly Ile Asp Ala Val Phe His His Tyr Glu Ser Val

8765 8770 8775

cac gat gga gct cgc gtc atg gtc aag ttc ccg aca gat gat caa 26379

His Asp Gly Ala Arg Val Met Val Lys Phe Pro Thr Asp Asp Gln

8780 8785 8790

ggc cga gcg ctc gat tcg ctt gcg aac agg ccg ctg caa cga ctc 26424

Gly Arg Ala Leu Asp Ser Leu Ala Asn Arg Pro Leu Gln Arg Leu

8795 8800 8805

cag agt cga cga atc gag gtg caa att cgg gag cgg cta caa gct 26469

Gln Ser Arg Arg Ile Glu Val Gln Ile Arg Glu Arg Leu Gln Ala

8810 8815 8820

gta ctg ccg tcc tat atg atg cca gtc cgc att gta gtc ttg gac 26514

Val Leu Pro Ser Tyr Met Met Pro Val Arg Ile Val Val Leu Asp

8825 8830 8835

gag atg cct atg aat gcg aac ggc aag gtt gac aga aaa gtg ctt 26559

Glu Met Pro Met Asn Ala Asn Gly Lys Val Asp Arg Lys Val Leu

8840 8845 8850

acc cgc aga gct aag atg att tcg agg gtc gag aca acc gct gaa 26604

Thr Arg Arg Ala Lys Met Ile Ser Arg Val Glu Thr Thr Ala Glu

8855 8860 8865

cgc gtt ggg cct cgc aac gag ata gag gct ctc ctc tgt gag gag 26649

Arg Val Gly Pro Arg Asn Glu Ile Glu Ala Leu Leu Cys Glu Glu

8870 8875 8880

ttt gct gaa gtg ctt ggt gtc gag gtt ggc att aat gac gac ttc 26694

Phe Ala Glu Val Leu Gly Val Glu Val Gly Ile Asn Asp Asp Phe

8885 8890 8895

ttc gat ctt ggc gga cac tct ctc atg gcc acg aag ctt gca gct 26739

Phe Asp Leu Gly Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala

8900 8905 8910

cgc agt agc cgt cgc ttc gat gcg aag gtc tct gtc aaa gac gtg 26784

Arg Ser Ser Arg Arg Phe Asp Ala Lys Val Ser Val Lys Asp Val

8915 8920 8925

ttt gat cat cct atc cta gcg gac cta gca gct tcg att cag cga 26829

Phe Asp His Pro Ile Leu Ala Asp Leu Ala Ala Ser Ile Gln Arg

8930 8935 8940

ggc tca act cca cac aac ccc atc ctc gca aca caa tat agc ggg 26874

Gly Ser Thr Pro His Asn Pro Ile Leu Ala Thr Gln Tyr Ser Gly

8945 8950 8955

cct gtg gag cag tct ttc gct cag ggt cgg ctg tgg ttc ctt gaa 26919

Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Glu

8960 8965 8970

cag ctg aac gtc agt tca aca tgg tat ctg caa cca atc gca gtg 26964

Gln Leu Asn Val Ser Ser Thr Trp Tyr Leu Gln Pro Ile Ala Val

8975 8980 8985

cgt atg cgc gga ccg ctt aag att gag gcg ctc gcg gcg gcg ttt 27009

Arg Met Arg Gly Pro Leu Lys Ile Glu Ala Leu Ala Ala Ala Phe

8990 8995 9000

cac gct ctg gag gag cgt cac gaa acc ctg cga acg acg ttt gaa 27054

His Ala Leu Glu Glu Arg His Glu Thr Leu Arg Thr Thr Phe Glu

9005 9010 9015

gag cac gac ggc att ggt atg cag gtt gtt cag cca cat cgc ccc 27099

Glu His Asp Gly Ile Gly Met Gln Val Val Gln Pro His Arg Pro

9020 9025 9030

aaa gaa ctc aga gtg att gat gta cag gct gag cat gat ggc gat 27144

Lys Glu Leu Arg Val Ile Asp Val Gln Ala Glu His Asp Gly Asp

9035 9040 9045

tat act cag gct ctg cac aca gag caa aca act acg ttc aat tta 27189

Tyr Thr Gln Ala Leu His Thr Glu Gln Thr Thr Thr Phe Asn Leu

9050 9055 9060

gaa acg gaa cca gga tgg agg gta tcg gtg ttt cgc ctg aac gaa 27234

Glu Thr Glu Pro Gly Trp Arg Val Ser Val Phe Arg Leu Asn Glu

9065 9070 9075

gat gac aac atc ctc tct ata gtg atg cac cat atc atc tct gat 27279

Asp Asp Asn Ile Leu Ser Ile Val Met His His Ile Ile Ser Asp

9080 9085 9090

ggt tgg tcg ttc gat atc ctg cgt aag gag atc aga gag ttt tac 27324

Gly Trp Ser Phe Asp Ile Leu Arg Lys Glu Ile Arg Glu Phe Tyr

9095 9100 9105

aac gcc gcg ctc aag ggc aag gac ccc ttg gcg caa atg agc ccc 27369

Asn Ala Ala Leu Lys Gly Lys Asp Pro Leu Ala Gln Met Ser Pro

9110 9115 9120

ttg cat atc caa tat cgc gac ttt tcc gtt tgg caa aag cag ctg 27414

Leu His Ile Gln Tyr Arg Asp Phe Ser Val Trp Gln Lys Gln Leu

9125 9130 9135

aat cag atc acc gag cat aaa cgg cag ctt gat tac tgg acg aag 27459

Asn Gln Ile Thr Glu His Lys Arg Gln Leu Asp Tyr Trp Thr Lys

9140 9145 9150

aac cta gcc gac aat act cca gcc gag ctc cca acc gat ctg cct 27504

Asn Leu Ala Asp Asn Thr Pro Ala Glu Leu Pro Thr Asp Leu Pro

9155 9160 9165

cgg cca gcc gtt cta tcc ggt aag gct gga gtc atc cag ctc tct 27549

Arg Pro Ala Val Leu Ser Gly Lys Ala Gly Val Ile Gln Leu Ser

9170 9175 9180

att aca ggt cca gtc tat gat cgt ctc cgc gcg ttc tgc cga gtc 27594

Ile Thr Gly Pro Val Tyr Asp Arg Leu Arg Ala Phe Cys Arg Val

9185 9190 9195

cac cag acc acc tta ttc acg gtg ctc ctc act gta ttt cga gcc 27639

His Gln Thr Thr Leu Phe Thr Val Leu Leu Thr Val Phe Arg Ala

9200 9205 9210

acc cac tat cgc ctc act gga gca gag gat gct acg att ggt acg 27684

Thr His Tyr Arg Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr

9215 9220 9225

cct atc gct aat cgt aac aga cca gag ctt gag aac ttg atc ggg 27729

Pro Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Leu Ile Gly

9230 9235 9240

ttt ttt gtt aac act cag tgc atg cgg att acc gta gaa gag gag 27774

Phe Phe Val Asn Thr Gln Cys Met Arg Ile Thr Val Glu Glu Glu

9245 9250 9255

gac acg ttc gag aca ctc atc cac cag gtt cgg act aca act aca 27819

Asp Thr Phe Glu Thr Leu Ile His Gln Val Arg Thr Thr Thr Thr

9260 9265 9270

gcc gct ttc gcc aac caa gac gta cct ttt gag cga att gtg tca 27864

Ala Ala Phe Ala Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser

9275 9280 9285

gcc cta ctc cca ggc tcc cga gac acg tcc cgc aac ccg ctc tct 27909

Ala Leu Leu Pro Gly Ser Arg Asp Thr Ser Arg Asn Pro Leu Ser

9290 9295 9300

cag atc atg ttt gcc gta cat tct cag aaa aac atc agc aag atc 27954

Gln Ile Met Phe Ala Val His Ser Gln Lys Asn Ile Ser Lys Ile

9305 9310 9315

gaa ctg gac ggc cta gag agc gag gcc att tca cga gcc aca tca 27999

Glu Leu Asp Gly Leu Glu Ser Glu Ala Ile Ser Arg Ala Thr Ser

9320 9325 9330

act cgt ttc gat cta gag ttc cat ctt ttc cag gaa gag aag ggc 28044

Thr Arg Phe Asp Leu Glu Phe His Leu Phe Gln Glu Glu Lys Gly

9335 9340 9345

cta ggc ggc att gta ttg ttt gcg gca gat ctg ttc gag ccg gag 28089

Leu Gly Gly Ile Val Leu Phe Ala Ala Asp Leu Phe Glu Pro Glu

9350 9355 9360

acg atc gac agc ctc gtc ttc gtc ttc caa gag atc ctc cgc cag 28134

Thr Ile Asp Ser Leu Val Phe Val Phe Gln Glu Ile Leu Arg Gln

9365 9370 9375

agt ctc gag aca ccc aag act cca att gcg gtc ttg cct ctt acc 28179

Ser Leu Glu Thr Pro Lys Thr Pro Ile Ala Val Leu Pro Leu Thr

9380 9385 9390

aat ggt att gcg cag ctt cgc agc atg tgt gtg cta gat att gag 28224

Asn Gly Ile Ala Gln Leu Arg Ser Met Cys Val Leu Asp Ile Glu

9395 9400 9405

aag acc gcc tac cct caa gac tcc agc gtc atc gat atc ttc cgc 28269

Lys Thr Ala Tyr Pro Gln Asp Ser Ser Val Ile Asp Ile Phe Arg

9410 9415 9420

cag cag gtt gct gcc cgc ccg gat gcc acg gcc gtc aca gat tct 28314

Gln Gln Val Ala Ala Arg Pro Asp Ala Thr Ala Val Thr Asp Ser

9425 9430 9435

acc tct cag ctc acc tac gca caa ctg gat ctc cac tct gac gag 28359

Thr Ser Gln Leu Thr Tyr Ala Gln Leu Asp Leu His Ser Asp Glu

9440 9445 9450

cta gcc agc tgg ctg cgt cag aaa aag atg gca ccc gag act ttg 28404

Leu Ala Ser Trp Leu Arg Gln Lys Lys Met Ala Pro Glu Thr Leu

9455 9460 9465

gtg ggt gtg cta gca cca cgg tct tgc caa acg atc gtt acc ttt 28449

Val Gly Val Leu Ala Pro Arg Ser Cys Gln Thr Ile Val Thr Phe

9470 9475 9480

ctt ggt att tta aag gcg agc tta gcc tat tta ccg cta gac gtc 28494

Leu Gly Ile Leu Lys Ala Ser Leu Ala Tyr Leu Pro Leu Asp Val

9485 9490 9495

aaa gtg ccg gtt gcc cgc ata gag gcc att ttg tcg tcc att tca 28539

Lys Val Pro Val Ala Arg Ile Glu Ala Ile Leu Ser Ser Ile Ser

9500 9505 9510

ggg cag aaa ctg att ctg ctt ggg cag gac gta cct gtc cca gaa 28584

Gly Gln Lys Leu Ile Leu Leu Gly Gln Asp Val Pro Val Pro Glu

9515 9520 9525

atc cag ctc cca gac gtc gat gtc gta cca atc agt gaa atc tta 28629

Ile Gln Leu Pro Asp Val Asp Val Val Pro Ile Ser Glu Ile Leu

9530 9535 9540

ggc cgc tct gtc cct tct cgt gct aca gat aag agt tta gga cca 28674

Gly Arg Ser Val Pro Ser Arg Ala Thr Asp Lys Ser Leu Gly Pro

9545 9550 9555

ttg gca aga aat ctt gcg tat gtt ctg ttc aca tct gga tcc aca 28719

Leu Ala Arg Asn Leu Ala Tyr Val Leu Phe Thr Ser Gly Ser Thr

9560 9565 9570

ggc aag ccc aag ggt gtc atg atc gag cac cgt agt att gtg cgc 28764

Gly Lys Pro Lys Gly Val Met Ile Glu His Arg Ser Ile Val Arg

9575 9580 9585

ctt gtc aaa gag aca aat ctt atc tct aag cta cca aac gcg cct 28809

Leu Val Lys Glu Thr Asn Leu Ile Ser Lys Leu Pro Asn Ala Pro

9590 9595 9600

cgc acg gca cat ctc acc aat ctc gtc ttt gac aac tct gca tgg 28854

Arg Thr Ala His Leu Thr Asn Leu Val Phe Asp Asn Ser Ala Trp

9605 9610 9615

gaa att tac tcc acc ctt ctc aac ggg gga acg cta gtc tgc atc 28899

Glu Ile Tyr Ser Thr Leu Leu Asn Gly Gly Thr Leu Val Cys Ile

9620 9625 9630

gac tat gcc acc gtt ctg gat agc aaa gcc ctc gag acc gtg ttc 28944

Asp Tyr Ala Thr Val Leu Asp Ser Lys Ala Leu Glu Thr Val Phe

9635 9640 9645

aag gag caa cgc att cag aca tct ctg atg cct cct gcg cta ctt 28989

Lys Glu Gln Arg Ile Gln Thr Ser Leu Met Pro Pro Ala Leu Leu

9650 9655 9660

aaa gag tgc tta gcc aac atg cct act atg ttc gat gac gta gag 29034

Lys Glu Cys Leu Ala Asn Met Pro Thr Met Phe Asp Asp Val Glu

9665 9670 9675

gtg ctc tac gcg ctt gga gat cga ttc gac aaa cag gat gcc atg 29079

Val Leu Tyr Ala Leu Gly Asp Arg Phe Asp Lys Gln Asp Ala Met

9680 9685 9690

aaa gcg cgc tcg ata gtc aag acc gcc gtc tac aac gcc tat ggt 29124

Lys Ala Arg Ser Ile Val Lys Thr Ala Val Tyr Asn Ala Tyr Gly

9695 9700 9705

ccc acg gaa aac acg gtc atc agt act atc tac gag att gcc aag 29169

Pro Thr Glu Asn Thr Val Ile Ser Thr Ile Tyr Glu Ile Ala Lys

9710 9715 9720

gac gat tcg ttc gtg aac ggt gtt ccc atc ggt cgg agc atc agc 29214

Asp Asp Ser Phe Val Asn Gly Val Pro Ile Gly Arg Ser Ile Ser

9725 9730 9735

aac tcc gga gcc ttc atc atg gac tcc cgg caa cag ctc gtc ccc 29259

Asn Ser Gly Ala Phe Ile Met Asp Ser Arg Gln Gln Leu Val Pro

9740 9745 9750

gtt ggc gtg cta ggc gag ctc gtc gtt tct ggc gat ggc ctt gcg 29304

Val Gly Val Leu Gly Glu Leu Val Val Ser Gly Asp Gly Leu Ala

9755 9760 9765

aga gga tat act gat ccc aca ctg gat gta aat cgc ttc gtt gag 29349

Arg Gly Tyr Thr Asp Pro Thr Leu Asp Val Asn Arg Phe Val Glu

9770 9775 9780

gtg act gtt gat ggc caa cat gtt aga gta tac cgg acc ggt gat 29394

Val Thr Val Asp Gly Gln His Val Arg Val Tyr Arg Thr Gly Asp

9785 9790 9795

cgc gta cgc ttc cgt cca aag gat ggt cag att gaa ttt ttt agt 29439

Arg Val Arg Phe Arg Pro Lys Asp Gly Gln Ile Glu Phe Phe Ser

9800 9805 9810

cgc atg gat cag caa gtc aag att cga ggc cat cgt atc gag ccg 29484

Arg Met Asp Gln Gln Val Lys Ile Arg Gly His Arg Ile Glu Pro

9815 9820 9825

gct gag gta gag cac gtt att ctc acc aac aag att atc cgt gat 29529

Ala Glu Val Glu His Val Ile Leu Thr Asn Lys Ile Ile Arg Asp

9830 9835 9840

gcg gct gtt gca atc cgg cga cct gag ggt caa gaa cca gaa atg 29574

Ala Ala Val Ala Ile Arg Arg Pro Glu Gly Gln Glu Pro Glu Met

9845 9850 9855

gtt gct ttc gtt act acc cat gaa aat act tct att gag aag cag 29619

Val Ala Phe Val Thr Thr His Glu Asn Thr Ser Ile Glu Lys Gln

9860 9865 9870

tca gtc gag gaa ttc gca gca cgg atc gag aat gaa gtc cgt cgc 29664

Ser Val Glu Glu Phe Ala Ala Arg Ile Glu Asn Glu Val Arg Arg

9875 9880 9885

tgg atc aag acc tta ctt ccg ctc tac atg gtt cct aca cag att 29709

Trp Ile Lys Thr Leu Leu Pro Leu Tyr Met Val Pro Thr Gln Ile

9890 9895 9900

gtt gta ttg gat cga atg cct gtc aat gct aac ggt aag gtt gac 29754

Val Val Leu Asp Arg Met Pro Val Asn Ala Asn Gly Lys Val Asp

9905 9910 9915

agg aaa gag ctc gcg caa aga gca caa acc cta cag aag agc gag 29799

Arg Lys Glu Leu Ala Gln Arg Ala Gln Thr Leu Gln Lys Ser Glu

9920 9925 9930

gcc ggt tcc ctt cct tcc gtg aga gtt cct ccc acc aac gac atg 29844

Ala Gly Ser Leu Pro Ser Val Arg Val Pro Pro Thr Asn Asp Met

9935 9940 9945

gag agg ata ttg tgc gaa gag ttt gcc gac gtt ctc ggc gtg gag 29889

Glu Arg Ile Leu Cys Glu Glu Phe Ala Asp Val Leu Gly Val Glu

9950 9955 9960

gtc ggc att acc gac aac ttc ttc gac ttt gga gga cac tca ctc 29934

Val Gly Ile Thr Asp Asn Phe Phe Asp Phe Gly Gly His Ser Leu

9965 9970 9975

atg gca acc aag ctc gca gcg cgt att agt cgc cgc gtg aac gcc 29979

Met Ala Thr Lys Leu Ala Ala Arg Ile Ser Arg Arg Val Asn Ala

9980 9985 9990

cga gta tcc gtc aag agc gtt ttc gac cac ccc gtc ctt gtt gac 30024

Arg Val Ser Val Lys Ser Val Phe Asp His Pro Val Leu Val Asp

9995 10000 10005

ctt gca tcc act att aaa caa gac tca atc atg cac aaa cct atc 30069

Leu Ala Ser Thr Ile Lys Gln Asp Ser Ile Met His Lys Pro Ile

10010 10015 10020

cca cag acc gcc tac acc ggg ccc gtg gaa cag tcc ttt gcc caa 30114

Pro Gln Thr Ala Tyr Thr Gly Pro Val Glu Gln Ser Phe Ala Gln

10025 10030 10035

ggc cgt ctc tgg ttc tta gac cag ctt aac ttc ggt gcc tcg tgg 30159

Gly Arg Leu Trp Phe Leu Asp Gln Leu Asn Phe Gly Ala Ser Trp

10040 10045 10050

tac ctc atg cct ctc gcg cta cgc ttg caa gga tct ctt cac gtc 30204

Tyr Leu Met Pro Leu Ala Leu Arg Leu Gln Gly Ser Leu His Val

10055 10060 10065

aag tcc ctc act act gcg ttg ttt gca cta gaa cag cgt cat gag 30249

Lys Ser Leu Thr Thr Ala Leu Phe Ala Leu Glu Gln Arg His Glu

10070 10075 10080

acc ctg aga aca aca ttt gag gaa caa gat ggc gtg ggc atc caa 30294

Thr Leu Arg Thr Thr Phe Glu Glu Gln Asp Gly Val Gly Ile Gln

10085 10090 10095

att gta cac cct gcc aac aag aaa gac ctt aga atc ctg gac gta 30339

Ile Val His Pro Ala Asn Lys Lys Asp Leu Arg Ile Leu Asp Val

10100 10105 10110

tct aaa gag caa aac agc gac tat gct aaa gtc ctg cac aag gag 30384

Ser Lys Glu Gln Asn Ser Asp Tyr Ala Lys Val Leu His Lys Glu

10115 10120 10125

cgc acg atc ccc att gat ctg act tcg gag cca ggt tgg agg gta 30429

Arg Thr Ile Pro Ile Asp Leu Thr Ser Glu Pro Gly Trp Arg Val

10130 10135 10140

tcg ctc att cgc ttg ggc gaa gac gat cat atc ctc tcc atc gtc 30474

Ser Leu Ile Arg Leu Gly Glu Asp Asp His Ile Leu Ser Ile Val

10145 10150 10155

atg cat cac att atc tca gat gga tgg tcc gtg gat gtt ctg cgc 30519

Met His His Ile Ile Ser Asp Gly Trp Ser Val Asp Val Leu Arg

10160 10165 10170

caa gaa ctg aag caa ttc tat act gct gcg ctc aag ggt caa gat 30564

Gln Glu Leu Lys Gln Phe Tyr Thr Ala Ala Leu Lys Gly Gln Asp

10175 10180 10185

cct ctg gcg cag att gac gct ctg cca atc caa tac cgc gac ttc 30609

Pro Leu Ala Gln Ile Asp Ala Leu Pro Ile Gln Tyr Arg Asp Phe

10190 10195 10200

tca ttg tgg cag aag ttg cca gat caa gtt gct gag cac caa cga 30654

Ser Leu Trp Gln Lys Leu Pro Asp Gln Val Ala Glu His Gln Arg

10205 10210 10215

cag ctc gag tac tgg gcc gag cag ttg gca gat aac act cca gcc 30699

Gln Leu Glu Tyr Trp Ala Glu Gln Leu Ala Asp Asn Thr Pro Ala

10220 10225 10230

gag ctc ctg acc gat cta ccc cgg ccg gac gtc cta tct ggc aag 30744

Glu Leu Leu Thr Asp Leu Pro Arg Pro Asp Val Leu Ser Gly Lys

10235 10240 10245

gct gga gcc gta caa ctc act atc gat ggt ccg gtg ttc gat cag 30789

Ala Gly Ala Val Gln Leu Thr Ile Asp Gly Pro Val Phe Asp Gln

10250 10255 10260

ctc cag gcg ttc tgc cga gca cat cag aca aca atg ttc acg gtt 30834

Leu Gln Ala Phe Cys Arg Ala His Gln Thr Thr Met Phe Thr Val

10265 10270 10275

ctg ctg gca gtc ttc cga aca act cat tac cgc ttg aca ggc gct 30879

Leu Leu Ala Val Phe Arg Thr Thr His Tyr Arg Leu Thr Gly Ala

10280 10285 10290

act gac gcc act atc ggt acc ccg att gcc aac cgt aac agg ccg 30924

Thr Asp Ala Thr Ile Gly Thr Pro Ile Ala Asn Arg Asn Arg Pro

10295 10300 10305

gaa ctt gaa aga ttg gtg ggc ttc ttc gtc aat act caa tgt atc 30969

Glu Leu Glu Arg Leu Val Gly Phe Phe Val Asn Thr Gln Cys Ile

10310 10315 10320

agg atc acg gta gac gtg gag gat aca ttt gaa gca ttg gta cga 31014

Arg Ile Thr Val Asp Val Glu Asp Thr Phe Glu Ala Leu Val Arg

10325 10330 10335

caa gtc cat tct acg tcg acg acg gcc ttt gcc aat cag gat gtt 31059

Gln Val His Ser Thr Ser Thr Thr Ala Phe Ala Asn Gln Asp Val

10340 10345 10350

ccg ttc gag cga att gtg tcc aca att cta cca ggc tcg cga gac 31104

Pro Phe Glu Arg Ile Val Ser Thr Ile Leu Pro Gly Ser Arg Asp

10355 10360 10365

gcc tcc cgg aat cct ctt gct caa ctc atg ttt gcc gtc cat tct 31149

Ala Ser Arg Asn Pro Leu Ala Gln Leu Met Phe Ala Val His Ser

10370 10375 10380

cag agg gat atc agt aaa ttc cag ctt gaa ggc cta gac acg aag 31194

Gln Arg Asp Ile Ser Lys Phe Gln Leu Glu Gly Leu Asp Thr Lys

10385 10390 10395

cct atc ccc acg gct gca tcc act cgc ttt gac att gag ttc cat 31239

Pro Ile Pro Thr Ala Ala Ser Thr Arg Phe Asp Ile Glu Phe His

10400 10405 10410

atg ttt cag cag gca gaa cgc ctt tct gga agg gtt ctt ttc gca 31284

Met Phe Gln Gln Ala Glu Arg Leu Ser Gly Arg Val Leu Phe Ala

10415 10420 10425

gag gat ctg ttc gaa cta gag act atc caa gga atg gtt gta atc 31329

Glu Asp Leu Phe Glu Leu Glu Thr Ile Gln Gly Met Val Val Ile

10430 10435 10440

ttc aaa gag att ctc cga aga ggc ctt gaa acg cca cag acc cca 31374

Phe Lys Glu Ile Leu Arg Arg Gly Leu Glu Thr Pro Gln Thr Pro

10445 10450 10455

ctt gcg gtt ctc cca ctc act gat ggg ctg gca cat ctt cgc agt 31419

Leu Ala Val Leu Pro Leu Thr Asp Gly Leu Ala His Leu Arg Ser

10460 10465 10470

caa ggc cta ctt gag att gag agg cca gag tat ccg cgc gac tca 31464

Gln Gly Leu Leu Glu Ile Glu Arg Pro Glu Tyr Pro Arg Asp Ser

10475 10480 10485

agc atg atc gac gtt ttc cgt gct cag gtt gcc gca tgc cct gac 31509

Ser Met Ile Asp Val Phe Arg Ala Gln Val Ala Ala Cys Pro Asp

10490 10495 10500

gcg att gcg gtc aaa gac tcc acc tca cag ctt acc tac agt caa 31554

Ala Ile Ala Val Lys Asp Ser Thr Ser Gln Leu Thr Tyr Ser Gln

10505 10510 10515

ctc gac gac caa tct gat aag atc act gcc tgg ctt ctc caa cgc 31599

Leu Asp Asp Gln Ser Asp Lys Ile Thr Ala Trp Leu Leu Gln Arg

10520 10525 10530

aaa atc cca gct gag agt ttg gtt gct gta tac gct cca aga acg 31644

Lys Ile Pro Ala Glu Ser Leu Val Ala Val Tyr Ala Pro Arg Thr

10535 10540 10545

tgt caa acc atc att aca ttc ttt ggt att ctc aag gct aat cta 31689

Cys Gln Thr Ile Ile Thr Phe Phe Gly Ile Leu Lys Ala Asn Leu

10550 10555 10560

gcc tac ctt cca ttg gat atc aat gtc cca gcc gcc cgt att gag 31734

Ala Tyr Leu Pro Leu Asp Ile Asn Val Pro Ala Ala Arg Ile Glu

10565 10570 10575

gca atc tta tca acc ata tct ggt cac aag cta gta ctg ctt ggg 31779

Ala Ile Leu Ser Thr Ile Ser Gly His Lys Leu Val Leu Leu Gly

10580 10585 10590

tct caa gtc tcc gct cct gcg gta caa ttg aag gac gtc gaa tat 31824

Ser Gln Val Ser Ala Pro Ala Val Gln Leu Lys Asp Val Glu Tyr

10595 10600 10605

gtt tgg att gat gaa gcc atg gct gag act gtt cgt aca tgc acc 31869

Val Trp Ile Asp Glu Ala Met Ala Glu Thr Val Arg Thr Cys Thr

10610 10615 10620

agc ccc gaa cct tct gcc aca agt ctt gca tac gtc atc ttc aca 31914

Ser Pro Glu Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr

10625 10630 10635

tcc gga tct aca ggt cta ccc aag ggc gtc aag gtc gag cac cgt 31959

Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Lys Val Glu His Arg

10640 10645 10650

ggt gtc gta cgt ctc gtc aag cag agt aat gtg gta gca aag atg 32004

Gly Val Val Arg Leu Val Lys Gln Ser Asn Val Val Ala Lys Met

10655 10660 10665

cct caa gca gca cgc gtt gcc cat cta tca aat atc gct ttc gac 32049

Pro Gln Ala Ala Arg Val Ala His Leu Ser Asn Ile Ala Phe Asp

10670 10675 10680

gct gcc acg tgg gag atc tat gct gcg ctc ctt aac ggc ggc tct 32094

Ala Ala Thr Trp Glu Ile Tyr Ala Ala Leu Leu Asn Gly Gly Ser

10685 10690 10695

ctc ata tgt att gac tat ttc act aca ttg gat agc aag gag ctt 32139

Leu Ile Cys Ile Asp Tyr Phe Thr Thr Leu Asp Ser Lys Glu Leu

10700 10705 10710

gaa gcc gtg ttt gca cga gaa aaa atc caa gcg gcc atg ctt ccg 32184

Glu Ala Val Phe Ala Arg Glu Lys Ile Gln Ala Ala Met Leu Pro

10715 10720 10725

ccg gcg ctg ctc aag cag tgt ttg gtc aac atc cct gcg act atc 32229

Pro Ala Leu Leu Lys Gln Cys Leu Val Asn Ile Pro Ala Thr Ile

10730 10735 10740

agc gcc tta gac gtg gta ctt gca gcg ggc gac cgt ttc gac agg 32274

Ser Ala Leu Asp Val Val Leu Ala Ala Gly Asp Arg Phe Asp Arg

10745 10750 10755

cgc gac gcg gcg gcg aca caa gcg ctc gtc gga ggc tgt gtc tac 32319

Arg Asp Ala Ala Ala Thr Gln Ala Leu Val Gly Gly Cys Val Tyr

10760 10765 10770

aac gcg tac ggc ccc acc gag aac acg act ctc agt acc atc tac 32364

Asn Ala Tyr Gly Pro Thr Glu Asn Thr Thr Leu Ser Thr Ile Tyr

10775 10780 10785

aat gtg gtc aaa ggc gat gcc aac gtc aac gga gtt cca atc ggt 32409

Asn Val Val Lys Gly Asp Ala Asn Val Asn Gly Val Pro Ile Gly

10790 10795 10800

cgc cct gtt agc aac tca ggt gcc tac atc atg gat ccc aat caa 32454

Arg Pro Val Ser Asn Ser Gly Ala Tyr Ile Met Asp Pro Asn Gln

10805 10810 10815

cag ctg gtc ccc aag ggt gtt atg gga gag ctt atc gtg gta gga 32499

Gln Leu Val Pro Lys Gly Val Met Gly Glu Leu Ile Val Val Gly

10820 10825 10830

gac gga gtc gct cga gga tat acc gat cca gca cta gat gtc aat 32544

Asp Gly Val Ala Arg Gly Tyr Thr Asp Pro Ala Leu Asp Val Asn

10835 10840 10845

cgt ttc att gag atc gcg att gat ggt gat cag gcg gtg cgc gcc 32589

Arg Phe Ile Glu Ile Ala Ile Asp Gly Asp Gln Ala Val Arg Ala

10850 10855 10860

tat cga aca ggt gat cgc gct cgt tac cga cct aaa gac ggt caa 32634

Tyr Arg Thr Gly Asp Arg Ala Arg Tyr Arg Pro Lys Asp Gly Gln

10865 10870 10875

atc gag ttc ttc ggc cgc atg gac caa caa atc aag att cgt ggc 32679

Ile Glu Phe Phe Gly Arg Met Asp Gln Gln Ile Lys Ile Arg Gly

10880 10885 10890

cat cgt att gaa cca gcc gaa gtg gag cac gcc gta ctt gat aac 32724

His Arg Ile Glu Pro Ala Glu Val Glu His Ala Val Leu Asp Asn

10895 10900 10905

agt atg gtg caa gat gct gcc gta att act cgc aag caa gat cag 32769

Ser Met Val Gln Asp Ala Ala Val Ile Thr Arg Lys Gln Asp Gln

10910 10915 10920

gag cta gag atg atc gct ttt gtt act aca cgt agc gat aag gaa 32814

Glu Leu Glu Met Ile Ala Phe Val Thr Thr Arg Ser Asp Lys Glu

10925 10930 10935

att gac aac gac gaa gcc agc aac caa gtc gaa gat tgg ggt aac 32859

Ile Asp Asn Asp Glu Ala Ser Asn Gln Val Glu Asp Trp Gly Asn

10940 10945 10950

cag ttt gag agt aac ata tat gct gag atc gaa gag atc gat tcc 32904

Gln Phe Glu Ser Asn Ile Tyr Ala Glu Ile Glu Glu Ile Asp Ser

10955 10960 10965

tct gcc att ggc aaa gac ttc atg ggc tgg acg tcc atg tac gac 32949

Ser Ala Ile Gly Lys Asp Phe Met Gly Trp Thr Ser Met Tyr Asp

10970 10975 10980

ggt agt gct atc gac aaa gac gaa atg cag gag tgg cta gac gac 32994

Gly Ser Ala Ile Asp Lys Asp Glu Met Gln Glu Trp Leu Asp Asp

10985 10990 10995

act atg agc aca ctg ctc gac ggt cga caa cca ggc cac gta ctc 33039

Thr Met Ser Thr Leu Leu Asp Gly Arg Gln Pro Gly His Val Leu

11000 11005 11010

gaa atc ggt act ggt act ggc atg atc ttg ttc aac cta gcc gag 33084

Glu Ile Gly Thr Gly Thr Gly Met Ile Leu Phe Asn Leu Ala Glu

11015 11020 11025

aga atg gga ttg aag agc tac gta ggc ctc gat ccc tcg gag aag 33129

Arg Met Gly Leu Lys Ser Tyr Val Gly Leu Asp Pro Ser Glu Lys

11030 11035 11040

gca acc tca ttc gtt aaa cag gcc atc aag tct cgc cca tct ctg 33174

Ala Thr Ser Phe Val Lys Gln Ala Ile Lys Ser Arg Pro Ser Leu

11045 11050 11055

gca ggc aag gct gag gtt cac gtc ggc aca gca aca gat gtg gct 33219

Ala Gly Lys Ala Glu Val His Val Gly Thr Ala Thr Asp Val Ala

11060 11065 11070

cga atg cga gat ctg cac ccc gaa gtg gtg gtt atc aat tcg gta 33264

Arg Met Arg Asp Leu His Pro Glu Val Val Val Ile Asn Ser Val

11075 11080 11085

gct caa tac ttt cca tcg cct gag tat ctg gcc gat gtc gtt ggc 33309

Ala Gln Tyr Phe Pro Ser Pro Glu Tyr Leu Ala Asp Val Val Gly

11090 11095 11100

gct ttg gtt cgc att cca ggc gtg aaa cga ctc ttc ttc ggc gac 33354

Ala Leu Val Arg Ile Pro Gly Val Lys Arg Leu Phe Phe Gly Asp

11105 11110 11115

ata cga tcc tac gct act aat aat cat ttc ctt gca gcc aga gcc 33399

Ile Arg Ser Tyr Ala Thr Asn Asn His Phe Leu Ala Ala Arg Ala

11120 11125 11130

cta cac aag cta gga gaa aag gca act agg gat act gta cga agc 33444

Leu His Lys Leu Gly Glu Lys Ala Thr Arg Asp Thr Val Arg Ser

11135 11140 11145

aaa atg gct gag ctc gaa ggc tac gag gag gaa ctg ctt gtc gac 33489

Lys Met Ala Glu Leu Glu Gly Tyr Glu Glu Glu Leu Leu Val Asp

11150 11155 11160

cca aca ttc ttc acc agt cta acg gcc aag ctt cac ggc cag gtc 33534

Pro Thr Phe Phe Thr Ser Leu Thr Ala Lys Leu His Gly Gln Val

11165 11170 11175

gag cac gtt gag atc cta cct aag cgt atg cag gcc acc aac gaa 33579

Glu His Val Glu Ile Leu Pro Lys Arg Met Gln Ala Thr Asn Glu

11180 11185 11190

ctc agc gca tac cga tac gcg gct ata gtc tac atc cgt gat cca 33624

Leu Ser Ala Tyr Arg Tyr Ala Ala Ile Val Tyr Ile Arg Asp Pro

11195 11200 11205

aaa cga gcg cag act gtg cag acg gtc aaa tcg gac gcc tgg gtc 33669

Lys Arg Ala Gln Thr Val Gln Thr Val Lys Ser Asp Ala Trp Val

11210 11215 11220

gat ttc agc acc tct caa atg gac cgc agt gtg ctc gtc agt ctc 33714

Asp Phe Ser Thr Ser Gln Met Asp Arg Ser Val Leu Val Ser Leu

11225 11230 11235

tta cag agc tca gat gct gaa gct atc gct gtc agc aat att ccc 33759

Leu Gln Ser Ser Asp Ala Glu Ala Ile Ala Val Ser Asn Ile Pro

11240 11245 11250

tac agc aag acg atc gtg gcg cgg cat atc gtt gag tca ctc agc 33804

Tyr Ser Lys Thr Ile Val Ala Arg His Ile Val Glu Ser Leu Ser

11255 11260 11265

gca gag gat tca caa gag atg ctg gac ggc cct gct tgg atc tca 33849

Ala Glu Asp Ser Gln Glu Met Leu Asp Gly Pro Ala Trp Ile Ser

11270 11275 11280

gca gtc cgc tcc agc gct gaa cag tgc gca tcc ttg tct gcg atc 33894

Ala Val Arg Ser Ser Ala Glu Gln Cys Ala Ser Leu Ser Ala Ile

11285 11290 11295

gac ctt gta cag gtt gct aaa gag aac ggc ttc cga gtg gag ctc 33939

Asp Leu Val Gln Val Ala Lys Glu Asn Gly Phe Arg Val Glu Leu

11300 11305 11310

agc tgc gca cga cag cgg tct cat aat gga gcg att gat gcg gta 33984

Ser Cys Ala Arg Gln Arg Ser His Asn Gly Ala Ile Asp Ala Val

11315 11320 11325

ttc cat cac tac aag cct gcg caa gaa ggt agc cgt gtc ttg cta 34029

Phe His His Tyr Lys Pro Ala Gln Glu Gly Ser Arg Val Leu Leu

11330 11335 11340

caa ttt cca acc gac aat cac atc cgg gca ggc tcg ctt acg aac 34074

Gln Phe Pro Thr Asp Asn His Ile Arg Ala Gly Ser Leu Thr Asn

11345 11350 11355

cga cca cta caa cgt ctc gag agt cga agg gtg gag aca aaa ctc 34119

Arg Pro Leu Gln Arg Leu Glu Ser Arg Arg Val Glu Thr Lys Leu

11360 11365 11370

aag gaa cac ctt ttt agt gtg ctt cca tcg tac atg att cca tca 34164

Lys Glu His Leu Phe Ser Val Leu Pro Ser Tyr Met Ile Pro Ser

11375 11380 11385

cat att gtg atg gtt gac cag atg cct ctg aat gcg aac ggc aag 34209

His Ile Val Met Val Asp Gln Met Pro Leu Asn Ala Asn Gly Lys

11390 11395 11400

gtt gac cgg aaa gcc ctg gca caa aga gct gaa gca gtt ctc aag 34254

Val Asp Arg Lys Ala Leu Ala Gln Arg Ala Glu Ala Val Leu Lys

11405 11410 11415

atc gag aaa cca gct tct gag aga gtc agt gca cgg aac gaa gtg 34299

Ile Glu Lys Pro Ala Ser Glu Arg Val Ser Ala Arg Asn Glu Val

11420 11425 11430

gaa gct gta ctg tgt gaa gag ttc acc gat gtc ctt ggt gtg gag 34344

Glu Ala Val Leu Cys Glu Glu Phe Thr Asp Val Leu Gly Val Glu

11435 11440 11445

gtc ggc att acc gac aac ttc ttc gac ctg ggc gga cac tcg ctc 34389

Val Gly Ile Thr Asp Asn Phe Phe Asp Leu Gly Gly His Ser Leu

11450 11455 11460

atg gcc acc aaa ctc gca gcc cgt atc agc aag cac ctc gac gct 34434

Met Ala Thr Lys Leu Ala Ala Arg Ile Ser Lys His Leu Asp Ala

11465 11470 11475

cgc gtc tct gtc aag gac gtt ttt gat tac cct gtc gtt gct gat 34479

Arg Val Ser Val Lys Asp Val Phe Asp Tyr Pro Val Val Ala Asp

11480 11485 11490

cta gca gcg tca att gaa cga aac tcg atc cct cat aac ccc att 34524

Leu Ala Ala Ser Ile Glu Arg Asn Ser Ile Pro His Asn Pro Ile

11495 11500 11505

ccc tcg acc aac tac tct gga ccc gtg gag caa tct ttc gcg caa 34569

Pro Ser Thr Asn Tyr Ser Gly Pro Val Glu Gln Ser Phe Ala Gln

11510 11515 11520

ggc cga ctt tgg ttc ctg gat caa ctg aat atg ggc gta tcg gaa 34614

Gly Arg Leu Trp Phe Leu Asp Gln Leu Asn Met Gly Val Ser Glu

11525 11530 11535

tta tat cta atg cct ctt gct cta cgc ctg cgc gga cct ctg cgc 34659

Leu Tyr Leu Met Pro Leu Ala Leu Arg Leu Arg Gly Pro Leu Arg

11540 11545 11550

gtt gac gcc ttc gca gct gca gta tct gct ctc gag gca cgc cat 34704

Val Asp Ala Phe Ala Ala Ala Val Ser Ala Leu Glu Ala Arg His

11555 11560 11565

gaa act ctc cga aca acc ttc atg gat cac gac ggt gta ggc atg 34749

Glu Thr Leu Arg Thr Thr Phe Met Asp His Asp Gly Val Gly Met

11570 11575 11580

caa gtc att ctg ccc agt aac agc aag aaa ctg aga gtc att gac 34794

Gln Val Ile Leu Pro Ser Asn Ser Lys Lys Leu Arg Val Ile Asp

11585 11590 11595

gcg tcc gag aac gac tat ata gac atc ctg cga cag gaa cgg aca 34839

Ala Ser Glu Asn Asp Tyr Ile Asp Ile Leu Arg Gln Glu Arg Thr

11600 11605 11610

gct cca ttc aat ctc acg acc gag cca ggg ttt agg atc gcc ctc 34884

Ala Pro Phe Asn Leu Thr Thr Glu Pro Gly Phe Arg Ile Ala Leu

11615 11620 11625

ttg cag ctg ggt caa acc gac ttc att ctg tca att gtc atg cac 34929

Leu Gln Leu Gly Gln Thr Asp Phe Ile Leu Ser Ile Val Met His

11630 11635 11640

cat atc ata tat gac ggt tgg tct att gat gtt cta tgc aga gag 34974

His Ile Ile Tyr Asp Gly Trp Ser Ile Asp Val Leu Cys Arg Glu

11645 11650 11655

ctt ggc cga ttc tat agc gct gca cta cag ggc cag gat cca ttg 35019

Leu Gly Arg Phe Tyr Ser Ala Ala Leu Gln Gly Gln Asp Pro Leu

11660 11665 11670

gcg caa gtg agc cct ctg cct atc cag tac cga gat ttc tct atc 35064

Ala Gln Val Ser Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ser Ile

11675 11680 11685

tgg caa aag cgg cca gag caa gtg gcc gag cat gag cgc cag cta 35109

Trp Gln Lys Arg Pro Glu Gln Val Ala Glu His Glu Arg Gln Leu

11690 11695 11700

caa tac tgg act gaa caa ctg gca gat agc tct cca gct gag ctt 35154

Gln Tyr Trp Thr Glu Gln Leu Ala Asp Ser Ser Pro Ala Glu Leu

11705 11710 11715

ctt acg gat cta ccc cgg cca ttg gtg cca acc ggt aag gcc ggt 35199

Leu Thr Asp Leu Pro Arg Pro Leu Val Pro Thr Gly Lys Ala Gly

11720 11725 11730

atc gtt caa ctc acg att gag ggc gca gtc tac gag cgc ctt cga 35244

Ile Val Gln Leu Thr Ile Glu Gly Ala Val Tyr Glu Arg Leu Arg

11735 11740 11745

gcc ttt tgc cgt gtt cat caa acg acc tcg ttc gct gta ctc ctc 35289

Ala Phe Cys Arg Val His Gln Thr Thr Ser Phe Ala Val Leu Leu

11750 11755 11760

gca gcc ttc cgt gcg acc cac tac cgt ctc acg ggc gct gag gat 35334

Ala Ala Phe Arg Ala Thr His Tyr Arg Leu Thr Gly Ala Glu Asp

11765 11770 11775

gct acc atc ggc tct cca att gct aat cgt aac cgc cca gaa cta 35379

Ala Thr Ile Gly Ser Pro Ile Ala Asn Arg Asn Arg Pro Glu Leu

11780 11785 11790

gaa agt ctg att ggc ttc ttt gtc aat acc cag tgt ata cgc gtg 35424

Glu Ser Leu Ile Gly Phe Phe Val Asn Thr Gln Cys Ile Arg Val

11795 11800 11805

aca atc aga gag gac gat acc ttc gac aaa ttg gtg cag caa gtc 35469

Thr Ile Arg Glu Asp Asp Thr Phe Asp Lys Leu Val Gln Gln Val

11810 11815 11820

cgg gca acg aca aca gcc gcg cag gtc aac cag gat gtc cca ttc 35514

Arg Ala Thr Thr Thr Ala Ala Gln Val Asn Gln Asp Val Pro Phe

11825 11830 11835

gaa cgc atc gtc tca gct ctg atg cct ggc tca aga gac acg tcc 35559

Glu Arg Ile Val Ser Ala Leu Met Pro Gly Ser Arg Asp Thr Ser

11840 11845 11850

cga aat cca cta gtg cag ctc agc ttt gct ctt cac tca cag cat 35604

Arg Asn Pro Leu Val Gln Leu Ser Phe Ala Leu His Ser Gln His

11855 11860 11865

gac ctt gga aga atc gat ctc cag gat ctg aca gga gaa gct ctt 35649

Asp Leu Gly Arg Ile Asp Leu Gln Asp Leu Thr Gly Glu Ala Leu

11870 11875 11880

ccc aca cca gtg ttc acc aga ctg gat gta gag ttc cat ctt ttc 35694

Pro Thr Pro Val Phe Thr Arg Leu Asp Val Glu Phe His Leu Phe

11885 11890 11895

cag caa gct gag aag ttc ggt ggt agc gta ttg ttt gca aca gac 35739

Gln Gln Ala Glu Lys Phe Gly Gly Ser Val Leu Phe Ala Thr Asp

11900 11905 11910

ttg ttt gag ccg gag act att caa gga ctg gtc tcc gtc ttc cag 35784

Leu Phe Glu Pro Glu Thr Ile Gln Gly Leu Val Ser Val Phe Gln

11915 11920 11925

gag gtc tta cgc cga gga ctt gag caa ccc caa acg cct att gca 35829

Glu Val Leu Arg Arg Gly Leu Glu Gln Pro Gln Thr Pro Ile Ala

11930 11935 11940

gtt ctg ccc ctt gac aac gcg tcc gag gat ctt cgg agc atg ggt 35874

Val Leu Pro Leu Asp Asn Ala Ser Glu Asp Leu Arg Ser Met Gly

11945 11950 11955

ctg ctt caa atg gag aga acc aac tat cca cgg gac tct agt gtg 35919

Leu Leu Gln Met Glu Arg Thr Asn Tyr Pro Arg Asp Ser Ser Val

11960 11965 11970

gtt gat gtc ttc cgt gat cag gtg gca gcc aat cct aga gca ata 35964

Val Asp Val Phe Arg Asp Gln Val Ala Ala Asn Pro Arg Ala Ile

11975 11980 11985

gcc gtc aag gat tca gtc tta gag ctg acc tac gct cag ctg gac 36009

Ala Val Lys Asp Ser Val Leu Glu Leu Thr Tyr Ala Gln Leu Asp

11990 11995 12000

gag aaa tct gac cag ttg gct gcc tgg ctc tgc caa cat aac att 36054

Glu Lys Ser Asp Gln Leu Ala Ala Trp Leu Cys Gln His Asn Ile

12005 12010 12015

ccg gca gag aca atc gtt ggc gtt ctg gct ccg aga tct tgc gag 36099

Pro Ala Glu Thr Ile Val Gly Val Leu Ala Pro Arg Ser Cys Glu

12020 12025 12030

aca att att gcc ttc ctc gga atc ctc aag gcc aac ctc gca tac 36144

Thr Ile Ile Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu Ala Tyr

12035 12040 12045

ttg cca tta gac gat aat gtt cca gct gct cgc att gag act ata 36189

Leu Pro Leu Asp Asp Asn Val Pro Ala Ala Arg Ile Glu Thr Ile

12050 12055 12060

ttg tca gca gtc cct ggc cac aca tta gtc cta ctc ggc tca cat 36234

Leu Ser Ala Val Pro Gly His Thr Leu Val Leu Leu Gly Ser His

12065 12070 12075

gtg gct gct cca agc att gga tta gca gat gct gaa ttc gtt aat 36279

Val Ala Ala Pro Ser Ile Gly Leu Ala Asp Ala Glu Phe Val Asn

12080 12085 12090

atc aat cat act tta ggc cac agt ttg caa ctc aac agc aca tgc 36324

Ile Asn His Thr Leu Gly His Ser Leu Gln Leu Asn Ser Thr Cys

12095 12100 12105

gcc aag ttg cag ccc tcc gct aca agc ctt gca tat gtt atc ttt 36369

Ala Lys Leu Gln Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe

12110 12115 12120

aca tct ggg tcg aca ggc aag cca aaa ggc gtt atg att gag cac 36414

Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Met Ile Glu His

12125 12130 12135

aga agc att gtg cga ctt gtc aaa aac agc aat acc ctc gcc aag 36459

Arg Ser Ile Val Arg Leu Val Lys Asn Ser Asn Thr Leu Ala Lys

12140 12145 12150

ctc cca cga gcc gct cgt gtc gct cat caa ttc aac ctt gcc ttc 36504

Leu Pro Arg Ala Ala Arg Val Ala His Gln Phe Asn Leu Ala Phe

12155 12160 12165

gat gca gca aac tac gag atc tat ggt aca ctg ctg aat ggg ggt 36549

Asp Ala Ala Asn Tyr Glu Ile Tyr Gly Thr Leu Leu Asn Gly Gly

12170 12175 12180

gcc ctg atc tgt gtc gat tac tcc acc ctc ttg gac att gat gct 36594

Ala Leu Ile Cys Val Asp Tyr Ser Thr Leu Leu Asp Ile Asp Ala

12185 12190 12195

ctc gtg gcc atg ttc aag cga gag aaa atc acc gca tcc tca ctg 36639

Leu Val Ala Met Phe Lys Arg Glu Lys Ile Thr Ala Ser Ser Leu

12200 12205 12210

tct cct ggt ttg ctc aag cag tgt gtg aac agt gca ccc gaa atg 36684

Ser Pro Gly Leu Leu Lys Gln Cys Val Asn Ser Ala Pro Glu Met

12215 12220 12225

ctc aag gct tta cag gtg atc tac aca ggt gga gac cga ctc gat 36729

Leu Lys Ala Leu Gln Val Ile Tyr Thr Gly Gly Asp Arg Leu Asp

12230 12235 12240

ggt cgc gat gcc att gag ttg caa gca ctt gtt ccc gga ggc gtt 36774

Gly Arg Asp Ala Ile Glu Leu Gln Ala Leu Val Pro Gly Gly Val

12245 12250 12255

tac aac atg tac gga cct acc gaa aac aca gtc atc agc acg ctt 36819

Tyr Asn Met Tyr Gly Pro Thr Glu Asn Thr Val Ile Ser Thr Leu

12260 12265 12270

tac aat ctc ggc gac aag cat tcg tat gtg aat ggc gtt ccc att 36864

Tyr Asn Leu Gly Asp Lys His Ser Tyr Val Asn Gly Val Pro Ile

12275 12280 12285

gga aca acc gtc agc aat tcg gga gcc tac gtc atg gat gcc ctg 36909

Gly Thr Thr Val Ser Asn Ser Gly Ala Tyr Val Met Asp Ala Leu

12290 12295 12300

caa cag ctc gtc cct gtc gga gta atg gga gag ctc gtc gtc act 36954

Gln Gln Leu Val Pro Val Gly Val Met Gly Glu Leu Val Val Thr

12305 12310 12315

ggg gat gga ctt gct cga ggg tac act gat ccg gaa cta gac cgc 36999

Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro Glu Leu Asp Arg

12320 12325 12330

aac cga ttc atc aag gtc aac att gat ggt cag gtc gtc agg gcg 37044

Asn Arg Phe Ile Lys Val Asn Ile Asp Gly Gln Val Val Arg Ala

12335 12340 12345

tac cga aca ggc gat cgc gtc cgc tac cga aga ata gac ggt caa 37089

Tyr Arg Thr Gly Asp Arg Val Arg Tyr Arg Arg Ile Asp Gly Gln

12350 12355 12360

tta gaa ttc ttc ggg cgc atg gat cag caa att aag att cga ggc 37134

Leu Glu Phe Phe Gly Arg Met Asp Gln Gln Ile Lys Ile Arg Gly

12365 12370 12375

ttc cgt atc gag acg gcg gaa gtt gag aac gcc atg ctc agt cac 37179

Phe Arg Ile Glu Thr Ala Glu Val Glu Asn Ala Met Leu Ser His

12380 12385 12390

agc gca gtt cgc aat gct gct gtt gtc gtc cct acc caa gac att 37224

Ser Ala Val Arg Asn Ala Ala Val Val Val Pro Thr Gln Asp Ile

12395 12400 12405

caa gag aag gga atg att ggt ttc gtg gtg att gaa aac aat aca 37269

Gln Glu Lys Gly Met Ile Gly Phe Val Val Ile Glu Asn Asn Thr

12410 12415 12420

ccc aag aac gag gag agc aag gaa gaa cac ttg cta caa act gaa 37314

Pro Lys Asn Glu Glu Ser Lys Glu Glu His Leu Leu Gln Thr Glu

12425 12430 12435

ttg gcg atc ctc aac cgg atg aag agc atc ctt cct cct tac atg 37359

Leu Ala Ile Leu Asn Arg Met Lys Ser Ile Leu Pro Pro Tyr Met

12440 12445 12450

ctc cca tct cgc atc atc atc ctt gat cag atg cct tcg aat ttc 37404

Leu Pro Ser Arg Ile Ile Ile Leu Asp Gln Met Pro Ser Asn Phe

12455 12460 12465

aat gga aag gtc gat cgt aaa gag ctt gat cgc atg gct cag agc 37449

Asn Gly Lys Val Asp Arg Lys Glu Leu Asp Arg Met Ala Gln Ser

12470 12475 12480

gta cct aga cag aag act acg gca ggg cgc ata gtt ccc cgc aat 37494

Val Pro Arg Gln Lys Thr Thr Ala Gly Arg Ile Val Pro Arg Asn

12485 12490 12495

gaa ttg gaa gct tcg ctc tgt aag gag ttc gct gaa gtg ctc ggc 37539

Glu Leu Glu Ala Ser Leu Cys Lys Glu Phe Ala Glu Val Leu Gly

12500 12505 12510

gtt gag gtc ggc atc act gac aat ttc ttc gac ctc ggt ggg cac 37584

Val Glu Val Gly Ile Thr Asp Asn Phe Phe Asp Leu Gly Gly His

12515 12520 12525

tcg cta ctg gca acc aag ctc gca gct cgc att agc cgc agg ctg 37629

Ser Leu Leu Ala Thr Lys Leu Ala Ala Arg Ile Ser Arg Arg Leu

12530 12535 12540

gat act cgc gtg tct gtt aaa gac gta ttc gat cag cct gtg ccc 37674

Asp Thr Arg Val Ser Val Lys Asp Val Phe Asp Gln Pro Val Pro

12545 12550 12555

gca gat cta gca ctc aag gtt tcg tct tac atc tcc caa ggt cat 37719

Ala Asp Leu Ala Leu Lys Val Ser Ser Tyr Ile Ser Gln Gly His

12560 12565 12570

gca atg gac aac gga acc ttg tcg aca acg aac agc atc ccc ttc 37764

Ala Met Asp Asn Gly Thr Leu Ser Thr Thr Asn Ser Ile Pro Phe

12575 12580 12585

cag cta cta cat ttt gaa gat tcg cag aaa ttt atc gac cgc gac 37809

Gln Leu Leu His Phe Glu Asp Ser Gln Lys Phe Ile Asp Arg Asp

12590 12595 12600

att gtc ccg caa ctt gct cat cag tca gct aaa att gtg gat gtc 37854

Ile Val Pro Gln Leu Ala His Gln Ser Ala Lys Ile Val Asp Val

12605 12610 12615

tat cct gtt acg tgg ata cag aag cac ttc ctt gtt gat cca gca 37899

Tyr Pro Val Thr Trp Ile Gln Lys His Phe Leu Val Asp Pro Ala

12620 12625 12630

aca gga ctt cca cgt aca cca tca ctc ttc ttt gtc gat ttc cca 37944

Thr Gly Leu Pro Arg Thr Pro Ser Leu Phe Phe Val Asp Phe Pro

12635 12640 12645

gcc aac gct gac tgc gac aaa att tgc aat gcg agc cgg tct ctc 37989

Ala Asn Ala Asp Cys Asp Lys Ile Cys Asn Ala Ser Arg Ser Leu

12650 12655 12660

att cag ctt ttc gat atc ttc agg act gtc ttt gtt cag gct gcc 38034

Ile Gln Leu Phe Asp Ile Phe Arg Thr Val Phe Val Gln Ala Ala

12665 12670 12675

ggc aat ttt tac caa gtc gtt ctg gaa gag ctt gac ata ccc atc 38079

Gly Asn Phe Tyr Gln Val Val Leu Glu Glu Leu Asp Ile Pro Ile

12680 12685 12690

tcg gtc atc gaa acc gaa gac atc agt act gca act cgc gtc ctg 38124

Ser Val Ile Glu Thr Glu Asp Ile Ser Thr Ala Thr Arg Val Leu

12695 12700 12705

aag gaa cag gat caa caa aat ccg ctc caa ttc gga caa gga ttc 38169

Lys Glu Gln Asp Gln Gln Asn Pro Leu Gln Phe Gly Gln Gly Phe

12710 12715 12720

tta cgc ttt gca gtc gtg aag acg agg tca gct gtg cgc ttg gta 38214

Leu Arg Phe Ala Val Val Lys Thr Arg Ser Ala Val Arg Leu Val

12725 12730 12735

ctt cgc atc tct cat tgc ttg tac gat ggc ttg agt ttc gag cat 38259

Leu Arg Ile Ser His Cys Leu Tyr Asp Gly Leu Ser Phe Glu His

12740 12745 12750

gtt gtg caa tca ctt cat gct ttg tat aat ggc gac cgc atc cca 38304

Val Val Gln Ser Leu His Ala Leu Tyr Asn Gly Asp Arg Ile Pro

12755 12760 12765

aca cag ccc aag ttc gtt cag tat gtt cag cat ctg act gac agc 38349

Thr Gln Pro Lys Phe Val Gln Tyr Val Gln His Leu Thr Asp Ser

12770 12775 12780

cgc aaa gaa ggt tac gat ttc tgg cta tct gtc ctg gag gag tcc 38394

Arg Lys Glu Gly Tyr Asp Phe Trp Leu Ser Val Leu Glu Glu Ser

12785 12790 12795

tcg atg aca gtc gta gag act ggc cgt cgc gct caa caa cta tca 38439

Ser Met Thr Val Val Glu Thr Gly Arg Arg Ala Gln Gln Leu Ser

12800 12805 12810

tca cct gag ggt gct tgg ttc gtc gag aag att atc aag gct gtt 38484

Ser Pro Glu Gly Ala Trp Phe Val Glu Lys Ile Ile Lys Ala Val

12815 12820 12825

atc cca gcc aac tca gat ggt att acg cag gca aca gta ttt acc 38529

Ile Pro Ala Asn Ser Asp Gly Ile Thr Gln Ala Thr Val Phe Thr

12830 12835 12840

act gct tcc acc atc ctg ctt gcc aga atg acc gga tca agc gac 38574

Thr Ala Ser Thr Ile Leu Leu Ala Arg Met Thr Gly Ser Ser Asp

12845 12850 12855

atc acc ttc agc cga ctc gta tct ggg cgt caa tct ttg ccg atc 38619

Ile Thr Phe Ser Arg Leu Val Ser Gly Arg Gln Ser Leu Pro Ile

12860 12865 12870

aat gac caa cat atc gtc ggc cct tgc aca aac atc gtc ccc gtt 38664

Asn Asp Gln His Ile Val Gly Pro Cys Thr Asn Ile Val Pro Val

12875 12880 12885

cgt att cgc atg act gat ggc act aat gca aga gag ctt ctc ggc 38709

Arg Ile Arg Met Thr Asp Gly Thr Asn Ala Arg Glu Leu Leu Gly

12890 12895 12900

atg gtg caa gac caa tac atc gac agc ttg cca ttt gaa acg cta 38754

Met Val Gln Asp Gln Tyr Ile Asp Ser Leu Pro Phe Glu Thr Leu

12905 12910 12915

ggg ttc gat gac atc aag gag aac tgc act aaa tgg cca gcg tcg 38799

Gly Phe Asp Asp Ile Lys Glu Asn Cys Thr Lys Trp Pro Ala Ser

12920 12925 12930

act acg aac tac ggc tgc tgc agc aca ttc cag aac ttc gag atg 38844

Thr Thr Asn Tyr Gly Cys Cys Ser Thr Phe Gln Asn Phe Glu Met

12935 12940 12945

cag cct caa agt caa gtc cag gac gaa cgt gtt cga ttg gct ggt 38889

Gln Pro Gln Ser Gln Val Gln Asp Glu Arg Val Arg Leu Ala Gly

12950 12955 12960

ttg aca aat ttc aaa gat gca gaa cta cta aat ggc gct acc gct 38934

Leu Thr Asn Phe Lys Asp Ala Glu Leu Leu Asn Gly Ala Thr Ala

12965 12970 12975

aca aac aag aga gtt cta gat gac gta cca atg cat gag att gat 38979

Thr Asn Lys Arg Val Leu Asp Asp Val Pro Met His Glu Ile Asp

12980 12985 12990

atg att gga atc cct gag ccg gat gga ctt cat gta cga gtt gtc 39024

Met Ile Gly Ile Pro Glu Pro Asp Gly Leu His Val Arg Val Val

12995 13000 13005

ctt acc gct agc agg cag att ttc gag gag gag gtt gtg gac cgc 39069

Leu Thr Ala Ser Arg Gln Ile Phe Glu Glu Glu Val Val Asp Arg

13010 13015 13020

atg cac gaa gag ttc tgc gat atc atc ttg ggt ttg aac aag atc 39114

Met His Glu Glu Phe Cys Asp Ile Ile Leu Gly Leu Asn Lys Ile

13025 13030 13035

ttg caa aaa tag 39126

Leu Gln Lys

13040

<210> 37

<211> 13041

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 37

Met Ala Ser Asp Ile Asn Thr His Pro Glu Gly Ala Thr Lys Phe Trp

1 5 10 15

Gln Gln His Phe Asp Gly Leu Asn Ala Ser Val Phe Pro Ala Leu Ser

20 25 30

Ser His Leu Thr Val Pro Arg Pro Asn Ala Gln Thr Ala His Arg Ile

35 40 45

Ser Tyr Ser Thr Leu Ala Lys Gln Lys Trp Asp Asn Thr Ser Leu Cys

50 55 60

Arg Ala Ala Leu Ala Ile Leu Leu Ala Arg Tyr Ser Asn Ala Ser Glu

65 70 75 80

Ala Leu Phe Gly Val Leu Val Glu Gln Phe Leu Pro Ser Asn Gly Glu

85 90 95

Gln Ala Ser Thr Glu Glu Ser Pro Gln Ser Ile Leu Pro Ile Arg Ile

100 105 110

Arg Leu Asp Leu Glu Glu Ala Gly Leu Gly Leu Leu Gln Ala Ile Asn

115 120 125

Thr Leu Asp Ala Ser Leu Arg Glu Trp Lys His Ile Gly Leu Asp Ala

130 135 140

Ile Arg Gly Thr Gly Glu Tyr Gly Ser Ala Gly Cys Glu Phe Gln Thr

145 150 155 160

Val Leu Ala Val Thr Thr Gly Lys Thr Pro Arg Thr His Arg Leu Ala

165 170 175

Ser Cys Thr Asp Arg Ala Leu Leu Leu Asp Cys Arg Met Asp Asp Asp

180 185 190

Ser Ala Thr Leu Leu Ala Arg Tyr Asp Pro Ser Val Ile Asp Asp Leu

195 200 205

Gln Val Ala Arg Phe Leu Lys Gln Leu Gly His Val Ile Glu Gln Leu

210 215 220

Arg Val Gln Ala Val Asp Leu Pro Leu Trp Glu Leu Gly Ile Val Thr

225 230 235 240

Gln Glu Asp Ser Ala Glu Ile Gln Lys Trp Asn Ser Gln Gln Leu Gln

245 250 255

Phe Ser Gln Glu Cys Ile His Asp Val Phe Ala Asn Arg Val Val Asp

260 265 270

Thr Pro Gln Lys Ile Ala Val Ser Ala Trp Asn Gly Glu Leu Thr Phe

275 280 285

Ala Glu Leu Asp Ser Phe Ser Ser Cys Leu Ala Gln His Ile Gln Ser

290 295 300

Leu Glu Leu Gly Asp Ala Lys Ala Ile Pro Leu Cys Phe Glu Lys Ser

305 310 315 320

Lys Trp Ala Ile Val Gly Met Leu Gly Val Leu Lys Ala Gly Arg Ala

325 330 335

Phe Thr Leu Ile Asp Pro Ser Asn Pro Pro Ala Arg Ala Arg Gln Ile

340 345 350

Cys Arg Gln Thr Ala Ala Thr Ile Ser Ile Ala Ser Pro Tyr Gln Cys

355 360 365

Asp Met Met Arg Ala Leu Val Pro Asp Cys Ile Val Val Asp Asp Asp

370 375 380

Phe Phe Lys Ser Leu Ala Phe Asp Thr Asp Gln Phe Gln Pro Thr Ala

385 390 395 400

Thr Pro Gln Thr Leu Ala Tyr Ile Leu Phe Thr Ser Gly Ser Thr Gly

405 410 415

Glu Pro Lys Gly Ser Met Met Glu His His Gly Phe Val Ser Cys Cys

420 425 430

Leu Glu Phe Gly Ala Ala Leu Gly Ile Asn Ser Asn Thr Arg Ala Leu

435 440 445

Gln Phe Ala Ser Tyr Ala Phe Gly Ala Cys Leu Leu Glu Ile Leu Thr

450 455 460

Thr Leu Met His Gly Gly Thr Val Cys Ile Pro Ser Asp Asp Glu Arg

465 470 475 480

Ile Asn Asp Ala Pro Gly Phe Ile Arg Arg Ala Asn Val Asn Trp Ala

485 490 495

Ile Leu Thr Pro Ser Phe Ile Gly Ala Ile Gln Pro Thr Thr Val Pro

500 505 510

Asn Leu Lys Thr Leu Val Leu Val Gly Glu Ala Met Pro Ser Asp Ile

515 520 525

Arg Asp Val Trp Ala Ser His Val Gln Leu Lys Asn Ala Tyr Gly Gln

530 535 540

Ser Glu Ser Ala Thr Ile Cys Ser Val Thr Glu Val Thr Pro Ala Thr

545 550 555 560

Val Glu Ala His Asn Ile Gly His Ala Val Gly Ala Arg Phe Trp Ile

565 570 575

Thr Asp Pro Asn Asn Pro Asn Lys Leu Ala Pro Ile Gly Cys Val Gly

580 585 590

Glu Leu Leu Val Glu Ser Pro Gly Ile Ala Arg Gly Tyr Leu Ile Pro

595 600 605

Leu Pro Ala Asp Ala Thr Pro Phe Ile Asp Thr Leu Pro Asp Trp Tyr

610 615 620

Pro Arg Thr Gln Pro Leu Asp Asn Phe Lys Phe Tyr Arg Thr Gly Asp

625 630 635 640

Leu Val Cys Tyr Arg Ser Asp Gly Thr Val Val Tyr Leu Gly Arg Arg

645 650 655

Asp Ser Gln Ile Lys Ile Arg Gly Gln Arg Val Glu Ile Gly Glu Val

660 665 670

Glu Thr Cys Leu Arg Gln Gln Leu Pro Ser Gln Leu Val Pro Val Val

675 680 685

Glu Ala Val Ser Leu Ser Gly Met Ser Lys Ser Met Thr Leu Ile Ala

690 695 700

Phe Leu Val Gly Glu Asn Thr Ile Leu Glu Glu Asp Val Tyr Val Leu

705 710 715 720

Glu Gly Ser Ala Ala Gln Arg Ile Ser Ser Lys Leu Arg Gln Ile Val

725 730 735

Pro Gly Tyr Cys Ile Pro Ser His Tyr Ile Arg Ile Asn His Leu Pro

740 745 750

Thr Thr Ala Thr Gly Lys Cys Asp Arg Lys Ala Leu Arg Ala Ile Gly

755 760 765

Thr Lys Leu Leu Arg Glu Ala Val Glu Gly Met Ala Ser Gln Glu Glu

770 775 780

Gln Glu Ser Ala Ser Leu Met Thr Glu Gly Ile Thr Leu Glu Arg Ile

785 790 795 800

Trp Phe Gln Ser Leu Gly Leu Lys Pro Asn Ser Thr Arg His Lys Ser

805 810 815

Asn Phe Phe Asn Leu Gly Gly Asp Ser Ile Ala Ala Ile Arg Met Val

820 825 830

Asn Met Ala Arg Ala Ala Gly Leu Leu Leu Ser Ile Ser Asp Ile Phe

835 840 845

Gln Asn Pro Ser Leu Ala Gly Leu Ile Asn Val Met Gln Gln Ser Ser

850 855 860

Thr Ala Gln Asp Ala Ile Pro Ala Thr Glu Tyr Ser Gly Pro Val Glu

865 870 875 880

Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp Gln Leu Thr Thr

885 890 895

Gly Ala Ser Trp Tyr Leu Met Pro Leu Ala Val Arg Ile His Gly Pro

900 905 910

Leu Arg Val Gln Ala Leu Ser Ser Ala Leu His Ala Leu Glu Gln Arg

915 920 925

His Glu Thr Leu Arg Thr Thr Phe Glu Gln Gln Asp Gly Met Gly Val

930 935 940

Gln Ile Val His Pro Ser Ser Lys Arg Glu Leu Arg Val Ile Asp Val

945 950 955 960

Ser Gly Lys Gln Asn Gly Gly Tyr Asp Gln Val Leu Lys Arg Glu Gln

965 970 975

Thr Thr Pro Ile Asp Leu Ala Lys Glu Pro Gly Trp Arg Ala Ala Leu

980 985 990

Leu Arg Val Gly Asp Asp Glu His Ile Leu Ser Ile Val Ile His His

995 1000 1005

Ile Ile Tyr Asp Gly Trp Ser Leu Gly Val Leu Arg Glu Glu Leu

1010 1015 1020

Gly Asp Leu Tyr Ala Ala Ala Leu Arg Gly Pro Asp Pro Leu Ala

1025 1030 1035

His Met Ala Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ser Val Trp

1040 1045 1050

Gln Lys Gln Pro Gln Gln Val Ala Gln His Gln Gln Gln Leu Val

1055 1060 1065

Tyr Trp Thr Lys Gln Leu Glu Asp Ser Ala Pro Ala Glu Leu Leu

1070 1075 1080

Thr Asp Phe Pro Arg Pro Ala Glu Leu Ser Gly Arg Ala Gly Glu

1085 1090 1095

Val Arg Phe Thr Ile Glu Gly Ser Val Phe Asp Ser Leu Leu Ala

1100 1105 1110

Phe Arg Arg Val His Gln Thr Thr Ser Phe Ala Val Leu Leu Ala

1115 1120 1125

Val Phe Arg Ala Ala His Tyr Arg Leu Thr Gly Thr Glu Asp Ala

1130 1135 1140

Thr Ile Gly Thr Pro Ile Ala Asn Arg Thr Arg Ala Glu Val Glu

1145 1150 1155

Lys Leu Ile Gly Phe Phe Val Asn Thr Gln Cys Met Arg Ile Ala

1160 1165 1170

Val Ala Asp Asp Asp Thr Phe Ala Ser Leu Val Ser Gln Val Trp

1175 1180 1185

Ser Val Ala Thr Ala Ala Phe Glu His Gln Asp Val Pro Phe Glu

1190 1195 1200

Arg Ile Val Ser Ala Leu Leu Pro Gly Ala Arg Asp Thr Ser Arg

1205 1210 1215

Asn Pro Leu Ala Gln Leu Leu Phe Ala Leu His Leu Glu Gln Asp

1220 1225 1230

Leu Asp Lys Ile Asn Leu Glu Gly Leu Ala Cys Glu Thr Val Pro

1235 1240 1245

Thr Pro Met Ala Thr Arg Phe Asp Val Glu Phe His Leu Phe Gln

1250 1255 1260

Glu Asp Asp Arg Leu Asn Gly Val Val Asn Phe Ser Thr Asp Leu

1265 1270 1275

Phe Glu Pro Gln Thr Ile His Ser Leu Val Ser Val Phe Gln Glu

1280 1285 1290

Ile Leu Arg Arg Gly Leu Asp Gln Pro Gln Thr Pro Ile Ala His

1295 1300 1305

Leu Gln Leu Thr Asp Gly Leu Glu Glu Leu Arg Asn Ala Gly Leu

1310 1315 1320

Leu Asp Ile Lys Arg Ile Asp Tyr Pro Arg Glu Ala Ser Val Val

1325 1330 1335

Asp Met Phe Gln Lys Gln Val Ala Ala Cys Pro Asn Val Thr Ala

1340 1345 1350

Val Lys Asp Ser Thr Ser Gln Leu Thr Tyr Ala Gln Leu Asp Gln

1355 1360 1365

Glu Ser Asp Lys Ile Ala Val Trp Leu Arg Lys Arg Asn Ile Pro

1370 1375 1380

Ala Glu Thr Leu Ile Ala Leu Leu Ala Pro Arg Ser Cys Asp Ser

1385 1390 1395

Val Ala Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu

1400 1405 1410

Pro Leu Asp Val Asn Val Pro Ala Ala Arg Ile Glu Ala Ile Leu

1415 1420 1425

Ser Thr Val Ala Gly His Lys Leu Val Leu Leu Gly Arg Asp Val

1430 1435 1440

Pro Leu Leu Gly Thr Gln Leu Ala Asp Leu Glu Leu Val Arg Ile

1445 1450 1455

Gly Glu Ala Leu Arg Gly Ser Ser Ser Gly Ser Val Ala Ala Asp

1460 1465 1470

Lys Ala Ile Arg Pro Thr Ala Thr Ser Leu Ala Tyr Val Ile Phe

1475 1480 1485

Thr Ser Gly Ser Thr Gly Gln Pro Lys Gly Ile Met Val Pro His

1490 1495 1500

Arg Ser Leu Val Asn Val Ile Lys Gln Arg Pro Ala Tyr Gly Asn

1505 1510 1515

Val Ala His Met Thr Asn Leu Ala Phe Asp Pro Ser Leu Phe Glu

1520 1525 1530

Met Cys Thr Ala Leu Phe Asn Gly Asn Thr Leu Ile Cys Ile Asp

1535 1540 1545

Thr Leu Val Ala Leu Asp Ala Thr Gln Leu Pro Thr Ile Phe Lys

1550 1555 1560

Gln Glu Ala Ile Arg Val Ala Met Met Thr Pro Ala Leu Leu Thr

1565 1570 1575

Arg Leu Leu Ala Gln Ala Thr Asp Ala Leu His Glu Leu Glu Ala

1580 1585 1590

Leu Tyr Val Leu Gly Asp Arg Phe Pro Pro Lys Asp Ala Ala Arg

1595 1600 1605

Ala Ser Glu Leu Val Lys Thr Ala Val Tyr Asn Ala Tyr Gly Pro

1610 1615 1620

Ser Glu Asn Ser Ile Cys Thr Thr Leu Phe His Ala Ala Thr Gly

1625 1630 1635

Ala Met Cys Thr Asn Gly Val Pro Val Gly Arg Val Ile Asn Asn

1640 1645 1650

Ser Gly Val Tyr Val Met Asp Pro Lys Gln Ser Leu Val Ser Tyr

1655 1660 1665

Gly Val Met Gly Glu Leu Val Val Ala Gly Glu Gly Leu Ala Ile

1670 1675 1680

Gly Tyr Thr Lys Pro Glu Leu Asn Glu Gly Arg Phe Leu Thr Leu

1685 1690 1695

Thr Met Asp Gly Lys Pro Val Arg Ala Phe Arg Thr Gly Asp Arg

1700 1705 1710

Val Arg Tyr Arg Pro Thr Asp Gly Gln Leu Glu Phe Phe Gly Arg

1715 1720 1725

Met Asp Phe Gln Ile Lys Ile Arg Gly His Arg Val Glu Leu Ala

1730 1735 1740

Glu Val Glu Arg Val Leu Asn Arg His Pro Ala Ile Lys Asp Ala

1745 1750 1755

Ile Thr Leu Leu Arg Gln His Gly Ser Ser Ala Gln Asp Thr Glu

1760 1765 1770

Leu Val Ser Phe Ile Val Leu Gly Glu Gln Lys Pro Val Lys Pro

1775 1780 1785

His Arg Asn Ala Thr Asp His Gly Gly Met Glu Ile Glu Gln Leu

1790 1795 1800

Asp Gln Lys Leu Glu Ala Asn Leu Arg Ala Met Met Gln Ala Thr

1805 1810 1815

Leu Pro Ser Tyr Met Val Pro Ser Arg Ile Ile Val Leu Asp His

1820 1825 1830

Met Pro Leu Asp Lys Asn Gly Lys Val Asp Arg Arg Gly Leu Thr

1835 1840 1845

Gly Leu Thr Leu Ser Pro Ala Met Glu Thr Ser Ser Arg Val Val

1850 1855 1860

Val Ala Ala Arg Asn Glu Ile Glu Ala Val Leu Cys Glu Glu Phe

1865 1870 1875

Ala His Ile Leu Gly Val Glu Ile Gly Val Thr Asp Asn Phe Phe

1880 1885 1890

Asp Leu Gly Gly His Ser Leu Met Ala Thr Thr Leu Ala Ala Arg

1895 1900 1905

Leu Ala Arg Arg Leu Asn Ala Ser Ile Ser Val Lys Asp Val Phe

1910 1915 1920

Asp Gln Pro Ile Val Ala Asn Leu Ala Ala Thr Ile Lys Arg Gly

1925 1930 1935

Ser Thr Pro His Asn Ala Ile Pro Pro Thr Lys Tyr Ser Gly Pro

1940 1945 1950

Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp Gln

1955 1960 1965

Leu Asn Leu Gly Ala Ala Trp Tyr His Met Pro Leu Ala Val Arg

1970 1975 1980

Leu Arg Gly Pro Leu His Leu Glu Ala Leu Thr Ala Ala Leu His

1985 1990 1995

Ala Leu Glu Glu Arg His Glu Thr Leu Arg Thr Val Phe Glu Glu

2000 2005 2010

Gln Asp Gly Val Gly Met Gln Ile Val Arg Pro Ser Ser Lys Thr

2015 2020 2025

Pro Leu Arg Ile Ile Asp Val Ser Thr Lys Glu Arg Gly Tyr Ala

2030 2035 2040

Glu Leu Leu Lys Gln Glu Gln Thr Thr Pro Phe Asp Leu Ala Thr

2045 2050 2055

Glu Leu Gly Trp Arg Val Ala Leu Leu Arg Gln Gly Lys Asp Asp

2060 2065 2070

His Ile Leu Ser Ile Val Ile His His Ile Ile Ser Asp Gly Trp

2075 2080 2085

Ser Leu Asp Ile Leu Cys Glu Glu Leu Gly Gln Phe Tyr Ala Ala

2090 2095 2100

Val Leu Arg Gly Gln Asp Pro Leu Ala Gln Ile Ser Pro Leu Pro

2105 2110 2115

Ile Gln Tyr Arg Asp Phe Ser Leu Trp Gln Lys Gln Pro Glu Gln

2120 2125 2130

Val Ala Glu His His Arg Gln Leu Glu Tyr Trp Thr Thr Gln Leu

2135 2140 2145

Glu Gly Ser Val Pro Ala Glu Leu Leu Thr Asp Leu Pro Arg Pro

2150 2155 2160

Thr Ile Gln Ser Gly Lys Ala Gly Val Ile Pro Ile Thr Val Asn

2165 2170 2175

Gly Pro Val Tyr Glu Arg Leu Arg Ala Phe Ser Arg Ala His Gln

2180 2185 2190

Thr Thr Ala Phe Ala Val Leu Leu Ala Ala Phe Arg Ala Thr His

2195 2200 2205

Tyr Arg Leu Ser Gly Val Ala Asp Ala Thr Ile Gly Thr Pro Ile

2210 2215 2220

Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Met Ile Gly Phe Phe

2225 2230 2235

Val Asn Ala Gln Cys Met Arg Ile Thr Val Glu Gln Asp Asp Thr

2240 2245 2250

Phe Glu Thr Leu Val Arg Gln Ile Arg Phe Thr Ala Thr Ala Ala

2255 2260 2265

Phe Ala Asn Gln Asp Val Pro Phe Glu His Ile Val Ser Ala Leu

2270 2275 2280

Met Pro Asp Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu

2285 2290 2295

Met Phe Ala Leu His Ala Tyr Lys Asp Leu Gly Lys Ile Glu Leu

2300 2305 2310

Glu Gly Tyr Val Ala Glu Pro Val His Thr Thr Leu Ser Thr Arg

2315 2320 2325

Phe Asp Leu Glu Phe His Met Phe Gln Glu Thr Asn His Leu Ser

2330 2335 2340

Gly Tyr Val Leu Tyr Ala Thr Asp Leu Phe Glu Pro Glu Ser Ile

2345 2350 2355

Glu Gly Met Val Ser Ile Phe Lys Glu Ile Leu Ala Arg Ala Leu

2360 2365 2370

Asp Gln Pro Gln Thr Pro Leu Ala Leu Leu Pro Leu Thr Asp Gly

2375 2380 2385

Leu Ala Glu Leu Arg Arg Arg Gly Leu Leu Glu Ile Glu Arg Pro

2390 2395 2400

Ser Tyr Pro Arg Glu Ser Ser Val Val Asp Val Phe Cys Ser Gln

2405 2410 2415

Val Ala Ala Ser Pro Asn Ala Thr Ala Val Lys Asp Ser Ile Ser

2420 2425 2430

Gln Leu Thr Tyr Ala Gln Leu Asn Glu Gln Ser Asp Lys Val Ala

2435 2440 2445

Ala Trp Leu His Gln Cys Asn Leu Pro Thr Glu Thr Leu Val Ala

2450 2455 2460

Val Leu Ala Pro Arg Ser Cys Gln Thr Val Val Ala Phe Leu Gly

2465 2470 2475

Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Val

2480 2485 2490

Pro Ala Ala Arg Ile Glu Ala Ile Leu Ser Glu Val Ser Gly His

2495 2500 2505

Ile Leu Val Leu Leu Gly Ser His Val Ser Ala Pro Lys Ile Glu

2510 2515 2520

Leu Ala Asp Val Glu Phe Val Lys Ile Asp Asn Thr Val Glu His

2525 2530 2535

Asn Leu Pro Gly Arg Ile Gly Ser Ala Pro Ser Ala Thr Ser Leu

2540 2545 2550

Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly

2555 2560 2565

Val Lys Val Glu His Arg Gly Ile Val Arg Leu Val Lys Glu Ser

2570 2575 2580

Asn Val Val Ala Lys Met Pro Gln Ala Ala Arg Ile Ala His Leu

2585 2590 2595

Ser Asn Ile Ala Phe Asp Ala Ala Thr Trp Glu Leu Tyr Ala Ala

2600 2605 2610

Leu Leu Asn Gly Gly Thr Leu Val Cys Ile Asn Tyr Leu Thr Thr

2615 2620 2625

Leu Asp Ser Lys Ala Leu Glu Ala Val Phe Glu Gln Glu Lys Ile

2630 2635 2640

Gln Ala Ala Met Leu Pro Pro Ala Leu Leu Lys Gln Tyr Leu Val

2645 2650 2655

Asn Ile Pro Ala Ala Ile Gly Ala Leu Glu Val Val Leu Val Ala

2660 2665 2670

Gly Asp Arg Phe Asp Arg Arg Asp Ala Ala Ala Thr Gln Ala Leu

2675 2680 2685

Val Gly Ala Gly Val Tyr Asn Ala Tyr Gly Pro Thr Glu Asn Thr

2690 2695 2700

Thr Leu Ser Thr Ile Tyr Asn Val Val Gln Gly Asp Ala Asn Val

2705 2710 2715

Asn Gly Val Pro Ile Gly Arg Pro Val Ser Asn Ser Gly Ala Tyr

2720 2725 2730

Ile Met Asn Met Asn Gln Glu Leu Val Pro Ile Gly Val Ile Gly

2735 2740 2745

Glu Leu Val Val Val Gly Asp Gly Val Ala Arg Gly Tyr Thr Asp

2750 2755 2760

Pro Ala Leu Asp Val Asn Arg Phe Val Asn Val Thr Ile Glu Gly

2765 2770 2775

Gln Thr Met Arg Ala Tyr Arg Thr Gly Asp Arg Ala Arg Tyr Arg

2780 2785 2790

Pro Lys Asp Ala Gln Ile Glu Phe Phe Gly Arg Met Asp Gln Gln

2795 2800 2805

Ile Lys Ile Arg Gly His Arg Ile Glu Pro Ala Glu Val Glu His

2810 2815 2820

Ala Leu Leu Asn Asn Asp Leu Leu Gln Asp Ala Ala Val Ile Ile

2825 2830 2835

Arg Lys Gln Gln Asn Asp Glu Leu Glu Met Val Ala Phe Val Glu

2840 2845 2850

Ala Asn Ser Asn Lys Ser Ile Glu Gln Glu Ala Ser Asn Gln Val

2855 2860 2865

Glu Asp Trp Gly Ala Gln Phe Glu Ser Asn Val Tyr Ala Glu Ile

2870 2875 2880

Glu Ala Ile Asp Ala Ser Ala Val Gly Asn Asp Phe Met Gly Trp

2885 2890 2895

Thr Ser Met Tyr Asp Gly Ser Ala Ile Asp Lys Ala Glu Met Gln

2900 2905 2910

Glu Trp Leu Asp Asp Thr Met Gln Thr Ile Leu Asp Gly Arg Pro

2915 2920 2925

Ala Gly Arg Val Leu Glu Ile Gly Thr Gly Thr Gly Met Ile Leu

2930 2935 2940

Phe Asn Leu Gly Glu Gly Leu Gln Ser Tyr Val Gly Leu Glu Pro

2945 2950 2955

Ser Thr Ser Ala Ala Ala Phe Val Asn Arg Arg Ile Gln Thr Leu

2960 2965 2970

Pro Ala Phe Ala Gly Lys Ala Glu Val His Val Gly Thr Ala Thr

2975 2980 2985

Asp Ile Ser Gln Leu Gln Asp Leu Arg Pro Glu Val Val Val Ile

2990 2995 3000

Asn Ser Val Ala Gln Tyr Phe Pro Ser Pro Glu Tyr Leu Ser Lys

3005 3010 3015

Val Leu Tyr Ala Leu Ala Gln Ile Pro Gly Val Lys Arg Leu Phe

3020 3025 3030

Phe Gly Asp Met Arg Ser Tyr Ala Ile Asn Asp Gln Phe Leu Ala

3035 3040 3045

Ala Arg Ala Leu His Asn Ile Gly Ser Lys Ala Thr Lys Ser Ala

3050 3055 3060

Ile Arg Ser Lys Met Val Asp Leu Glu Asn Ser Glu Glu Glu Leu

3065 3070 3075

Leu Val Asp Pro Thr Phe Phe Thr Asn Leu Ala Thr Glu Leu Pro

3080 3085 3090

Glu Val Glu His Val Glu Ile Leu Pro Lys Arg Met Gln Ala Thr

3095 3100 3105

Asn Glu Leu Ser Ala Tyr Arg Tyr Ala Ala Val Val His Ile Arg

3110 3115 3120

Asp Ser Ser Glu Arg Ala Gln Thr Val His Ala Ile Lys Ser Ser

3125 3130 3135

Ala Trp Val Asp Phe Ser Lys Ser Gln Met Asp Arg Lys Ala Leu

3140 3145 3150

Ile Ser Leu Leu Gln Ser Ser Val Asn Thr Glu Ala Val Ala Ile

3155 3160 3165

Gly Asn Ile Pro Tyr Ser Lys Thr Ile Met Ala Arg His Val Val

3170 3175 3180

Gln Ser Leu Asp Glu Asp Asn Ala Asp Lys Asp Ile Ala Gln Asp

3185 3190 3195

Lys Pro Asp Lys Pro Thr Trp Ile Ser Ala Val Arg Ser Asn Ala

3200 3205 3210

Glu His Cys Pro Ser Leu Ser Ala Leu Asp Leu Val Gln Leu Gly

3215 3220 3225

Glu Glu Ala Gly Phe Cys Val Glu Leu Ser Trp Ala Gln Gln Arg

3230 3235 3240

Ser His His Gly Ala Ile Asp Ala Val Phe His His Tyr Gln Pro

3245 3250 3255

Ala Arg Glu Gly Ser Arg Val Leu Phe Gln Phe Pro Thr Asp Thr

3260 3265 3270

Tyr Arg Arg Gln Ser Gly Pro Leu Thr Asn Arg Pro Leu Gln Arg

3275 3280 3285

Ile Gln Ser Arg Arg Met Glu Thr Gln Val Arg Glu Lys Leu Arg

3290 3295 3300

Ala Val Leu Pro Ser Tyr Met Ile Pro Ser Leu Ile Val Leu Val

3305 3310 3315

Asp Gln Met Pro Leu Asn Pro Asn Gly Lys Val Asp Arg Lys Ala

3320 3325 3330

Leu Glu Arg Arg Ala Gln Ala Val Leu Arg Val Glu Lys Pro Thr

3335 3340 3345

Ser Glu Arg Val Gly Ala Arg Asn Glu Thr Glu Ala Val Leu Cys

3350 3355 3360

Glu Glu Phe Thr Asp Val Leu Gly Leu Glu Val Gly Ile Thr Asp

3365 3370 3375

Asn Phe Phe Asp Leu Gly Gly His Ser Leu Met Ala Thr Lys Leu

3380 3385 3390

Ala Ala Arg Ile Ser Arg Arg Leu Asp Ala Arg Val Ser Val Lys

3395 3400 3405

Asp Val Phe Asp Gln Pro Val Ile Val Asp Leu Ala Ala Ser Ile

3410 3415 3420

Arg Arg Gly Ser Thr Pro His Asn Pro Ile Thr Pro Thr Glu Tyr

3425 3430 3435

Ser Gly Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe

3440 3445 3450

Leu Asp Gln Leu Asn Leu Gly Ala Ser Leu Tyr Leu Met Pro Leu

3455 3460 3465

Ala Leu Arg Leu Arg Gly Pro Leu Arg Ile Asp Ala Leu Thr Ala

3470 3475 3480

Ala Leu Phe Ala Leu Glu Gln Arg His Glu Thr Leu Arg Thr Val

3485 3490 3495

Phe Lys Glu Gln Asp Gly Val Gly Ile Gln Ile Ile Gln Pro Ser

3500 3505 3510

Gln Lys Lys Lys Leu Arg Thr Ile Asp Val Ser Ala Gly Asp Phe

3515 3520 3525

Ser Glu Ala Leu His His Glu Arg Thr Ala Pro Phe Asp Leu Ala

3530 3535 3540

Ser Glu Pro Gly Phe Arg Val Ala Leu Leu Gln Leu Glu Pro Ser

3545 3550 3555

Asp His Val Leu Ser Ile Val Met His His Ile Ile Tyr Asp Gly

3560 3565 3570

Trp Ser Ile Asp Ile Leu Cys Gln Glu Leu Gly Gln Phe Tyr Ala

3575 3580 3585

Ala Ala Ile Gln Gly Gln Asp Pro Leu Gly Gln Val Ser Pro Leu

3590 3595 3600

Pro Ile Gln Tyr Arg Asp Phe Ser Val Trp Gln Lys Gln Pro Glu

3605 3610 3615

Gln Val Ala Glu His Glu Arg Gln Leu Ala Tyr Trp Ile Asp Gln

3620 3625 3630

Leu Ala Asp Ser Ala Pro Ala Glu Phe Leu Val Asp Leu Pro Arg

3635 3640 3645

Pro Pro Val Leu Ser Gly Asp Ala Gly Leu Val His Leu Thr Ile

3650 3655 3660

Asp Gly Pro Ile Tyr Asp Arg Leu Arg Ala Phe Cys Arg Val His

3665 3670 3675

Gln Thr Thr Thr Phe Ala Val Leu Leu Ala Ala Phe Arg Ala Thr

3680 3685 3690

His Tyr Arg Leu Thr Gly Ala Glu Asp Ala Thr Val Gly Thr Pro

3695 3700 3705

Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Leu Val Gly Phe

3710 3715 3720

Phe Val Asn Thr Gln Cys Met Arg Ile Ser Val Gly Asp Asp Asp

3725 3730 3735

Thr Phe Glu Gln Leu Val Arg Gln Val Arg Ser Thr Ala Thr Ala

3740 3745 3750

Ala Phe Ala Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Thr

3755 3760 3765

Leu Leu Pro Gly Ser Arg Asp Thr Ala Arg Asn Pro Leu Val Gln

3770 3775 3780

Leu Met Phe Ala Val His Ser Leu Lys Asp Leu Gly Lys Ile Gln

3785 3790 3795

Phe Glu Gly Leu Val Gly Glu Thr Ile Pro Thr Ala Ser Phe Thr

3800 3805 3810

Arg Phe Asp Val Glu Phe His Leu Phe Gln Glu Val Gly Arg Leu

3815 3820 3825

Ser Gly Asn Val Leu Phe Ser Thr Asp Leu Phe Glu Pro Glu Thr

3830 3835 3840

Ile Gln Gly Met Val Ser Val Phe Met Glu Ile Leu Arg Gly Ala

3845 3850 3855

Leu Asp Gln Pro Gln Ile Pro Ile Ala Val Leu Pro Leu Thr Asp

3860 3865 3870

Gly Leu Thr Glu Leu Arg Asn Arg Gly Leu Leu Glu Val Glu Gln

3875 3880 3885

Pro Gln Tyr Pro Arg Asp Ser Ser Val Ile Asp Val Phe Arg Ala

3890 3895 3900

Gln Val Val Ala Cys Pro Asp Ala Ile Ala Val Lys Asp Ser Thr

3905 3910 3915

Ser Gln Leu Thr Tyr Ala Gln Leu Asp Glu Gln Ser Asp Glu Val

3920 3925 3930

Ala Val Trp Leu His Gln Arg Lys Leu Pro Ala Glu Ser Leu Val

3935 3940 3945

Ala Val Leu Ala Pro Arg Ser Cys Glu Thr Ile Ile Thr Phe Phe

3950 3955 3960

Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Ile Asn

3965 3970 3975

Val Pro Ala Ala Arg Ile Gln Ala Ile Leu Ser Ser Val Ala Gly

3980 3985 3990

Lys Lys Ile Leu Leu Leu Gly Ser Asp Gln Ala Gln Pro Glu Ile

3995 4000 4005

Arg Leu Asp Asp Val Glu Phe Val Gln Ile Asn Glu Thr Ile Asp

4010 4015 4020

His Asn Met Ala Lys Asp Asn Thr Thr Arg Ser Gly Pro Leu Ala

4025 4030 4035

Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Gln

4040 4045 4050

Pro Lys Gly Val Lys Val Glu His Arg Gly Ile Val Arg Leu Val

4055 4060 4065

Lys Asn Ser Asn Val Val Ala Lys Met Pro Glu Ala Ala Cys Val

4070 4075 4080

Ala His Leu Ser Asn Leu Ala Phe Asp Ala Ala Thr Trp Glu Ile

4085 4090 4095

Tyr Ala Ala Leu Leu Asn Gly Gly Ser Leu Ile Cys Ile Asp Tyr

4100 4105 4110

Phe Thr Thr Leu Asp Ser Lys Val Leu Glu Ala Val Phe Glu Arg

4115 4120 4125

Glu Gln Ile Arg Ala Ala Met Phe Pro Pro Ala Leu Leu Lys Gln

4130 4135 4140

Cys Leu Leu Asn Ile Pro Thr Thr Ile Ser Ala Leu Asp Val Ile

4145 4150 4155

Leu Ala Ala Gly Asp Arg Phe Asp Arg Arg Asp Ala Ile Ala Ala

4160 4165 4170

Gln Ala Leu Val Gly Gly Gly Val Tyr Asn Ala Tyr Gly Pro Thr

4175 4180 4185

Glu Asn Thr Thr Leu Ser Thr Ile Tyr Asn Val Val Asp Gly Asp

4190 4195 4200

Thr Asn Val Asn Gly Ile Pro Ile Gly Leu Pro Val Ser Asn Ser

4205 4210 4215

Gly Val Tyr Val Met Asp Pro Asn Gln Gln Leu Val Pro Leu Gly

4220 4225 4230

Val Met Gly Glu Leu Val Val Val Gly Asp Gly Val Ala Arg Gly

4235 4240 4245

Tyr Thr Asp Pro Ala Leu Asp Val Asp Arg Phe Ile Lys Val Glu

4250 4255 4260

Ile Asp Gly Gln Ile Val Arg Ala Tyr Arg Thr Gly Asp Arg Val

4265 4270 4275

Arg His Arg Pro Lys Asp Gly Gln Ile Glu Phe Phe Gly Arg Met

4280 4285 4290

Asp Gln Gln Val Lys Ile Arg Gly His Arg Ile Glu Leu Ala Glu

4295 4300 4305

Val Glu His Val Ile Leu Asp Asn Ser Leu Val Gln Asp Ala Ala

4310 4315 4320

Val Ile Val His Lys Gln Ala Asp Gln Glu Ile Glu Met Ile Ala

4325 4330 4335

Phe Ala Ile Val Arg Gly Asp Asn Asp Ser Lys His Pro Glu Lys

4340 4345 4350

Asp Ile Leu Asp Arg Val Lys Ala Leu Leu Pro Ser Tyr Met Val

4355 4360 4365

Pro Ala Gln Met Val Leu Leu Asn Ser Met Pro Leu Asn Ala Asn

4370 4375 4380

Gly Lys Val Asp Arg Lys Glu Leu Ala Lys Arg Ala Gly Thr Val

4385 4390 4395

Pro Arg Ser Glu Met Ala Tyr Val Ala Pro Glu Arg Val Pro Pro

4400 4405 4410

Arg Asn Glu Ile Glu Thr Ile Leu Cys Glu Glu Tyr Ala Glu Val

4415 4420 4425

Leu Gly Val Glu Val Gly Val Met Asp Asn Phe Phe Asp Leu Gly

4430 4435 4440

Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala Arg Ala Thr Arg

4445 4450 4455

Arg Leu Asp Ala Lys Leu Ser Val Lys Asp Ile Phe Asp Tyr Pro

4460 4465 4470

Ile Leu Ala Asn Leu Ala Ala Ala Val Gln Arg Gly Ser Thr Pro

4475 4480 4485

His Asn Ala Ile Leu Ala Thr Thr Tyr Ser Gly Pro Val Glu Gln

4490 4495 4500

Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp Gln Leu Asn Val

4505 4510 4515

Gly Ser Asn Trp Tyr Leu Gln Pro Ile Ala Ile Arg Ile Arg Gly

4520 4525 4530

Ser Leu Asn Ile Asn Ala Leu Thr Thr Ala Leu His Ala Leu Glu

4535 4540 4545

Gln Arg His Glu Thr Leu Arg Thr Thr Phe Glu Glu Glu Asp Gly

4550 4555 4560

Val Gly Met Gln Val Val Gln Glu Tyr Asp Pro Ile Glu Leu Arg

4565 4570 4575

Ile Met Asp Ile Ala Ala Asp Tyr Asp Gly Asp Tyr Thr Glu Ala

4580 4585 4590

Leu Lys Gly Glu Gln Thr Thr Pro Phe Asp Leu Glu Ser Glu Pro

4595 4600 4605

Gly Trp Arg Val Ser Leu Leu Arg Met Asn Asp Asn Asp His Ile

4610 4615 4620

Leu Ser Leu Val Leu His His Ile Ile Ser Asp Gly Trp Ser Val

4625 4630 4635

Asp Val Leu Arg Gln Glu Leu Lys Gln Phe Tyr Ala Ala Ala Leu

4640 4645 4650

Gln Gly Leu Asp Pro Leu Ser Gly Ala Asp Pro Leu Pro Ile Gln

4655 4660 4665

Tyr Arg Asp Phe Ser Leu Trp Gln Lys Gln Pro Glu Gln Val Ala

4670 4675 4680

Glu His Glu Arg Gln Leu Lys Tyr Trp Val Glu Gln Leu Ala Asp

4685 4690 4695

Asn Ser Pro Ala Thr Leu Leu Ala Asp Arg Pro Arg Pro Ser Val

4700 4705 4710

Leu Ser Gly Gln Ala Gly Ser Val Pro Leu Ser Ile Glu Gly Gln

4715 4720 4725

Val Tyr Glu Lys Leu Gln Ala Phe Cys Arg Ala His Gln Thr Thr

4730 4735 4740

Ser Phe Ser Val Leu Leu Ala Ala Phe Arg Ala Ala His Phe Arg

4745 4750 4755

Leu Thr Gly Val Asp Asp Ala Thr Ile Gly Ile Pro Ile Ala Asn

4760 4765 4770

Arg Asn Arg Pro Glu Leu Glu His Leu Ile Gly Phe Phe Val Asn

4775 4780 4785

Arg Gln Cys Met Arg Ile Thr Val Gly Glu Asp Asp Thr Phe Glu

4790 4795 4800

Ser Leu Ile Arg Gln Val His Ser Thr Ala Thr Ala Ala Tyr Ala

4805 4810 4815

Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Ser Leu Leu Ser

4820 4825 4830

Gly Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu Val Phe

4835 4840 4845

Ala Val His Ser Gln Lys Asn Leu Gly Lys Phe Glu Leu Gln Asp

4850 4855 4860

Leu Thr Ser Glu Pro Val Ala Gly Ala Ile Ser Thr Arg Phe Asp

4865 4870 4875

Ala Glu Phe His Leu Phe Gln Glu Glu Glu Arg Leu Asn Gly Val

4880 4885 4890

Val Tyr Tyr Ala Thr Asp Leu Phe Asp Ala Glu Thr Ile Gln Gly

4895 4900 4905

Val Val Ser Val Phe Gln Glu Ile Leu Arg Arg Gly Leu Asn His

4910 4915 4920

Pro Arg Thr Pro Ile Ala Ala Leu Ser Leu Thr Asp Gly Leu Asp

4925 4930 4935

Asn Leu Arg Lys Met Asn Leu Val His Phe Lys Arg Thr Asp Tyr

4940 4945 4950

Pro Arg Asp Ser Ser Met Val Asp Ile Phe Arg Glu Gln Val Ala

4955 4960 4965

Thr Tyr Pro Asp Val Ile Ala Val Lys Asp Ser Thr Leu Gln Leu

4970 4975 4980

Thr Tyr Ala Gln Leu Asp Gln Gln Ser Asp Glu Ile Ala Thr Trp

4985 4990 4995

Leu Arg Asn Lys Lys Met Ala Pro Glu Thr Leu Val Gly Val Leu

5000 5005 5010

Ala Pro Arg Ser Cys Gln Thr Ile Val Ala Phe Leu Gly Val Leu

5015 5020 5025

Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Ala Pro Met

5030 5035 5040

Ala Arg Val Glu Thr Ile Met Ser Ser Val Pro Gly Ser Lys Leu

5045 5050 5055

Leu Leu Leu Gly Ser Asp Val Pro Ala Gln Glu Ile Gln Leu Gln

5060 5065 5070

Asn Val Glu Leu Val Arg Ile Glu Asp Thr Leu Gly His Ala Ala

5075 5080 5085

Ser Ala Gly Thr Ala Thr Thr Glu Pro Ser Pro Thr Ser Leu Ala

5090 5095 5100

Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val

5105 5110 5115

Met Val Glu His Arg Ser Val Ile Arg Leu Val Arg Lys Glu Ser

5120 5125 5130

Asn Ser Met Ser Lys Met Ser Ser Arg Ala Arg Val Ala His Leu

5135 5140 5145

Thr Asn Ile Ala Phe Asp Val Ser Ala Trp Glu Val Tyr Ala Thr

5150 5155 5160

Leu Leu Asn Gly Gly Thr Leu Val Cys Val Asp Tyr Phe Thr Ser

5165 5170 5175

Phe Asp Ala Lys Ala Leu Gly Leu Leu Phe Glu Arg Glu Gln Ile

5180 5185 5190

Thr Ala Ala Met Ile Thr Pro Thr Leu Leu Lys Gln Cys Ile Thr

5195 5200 5205

Ile Val Pro Glu Ala Leu Arg Lys Leu Ser Val Leu Tyr Thr Gly

5210 5215 5220

Gly Asp Arg Phe Asp Arg Arg Asp Ala Ile Ala Thr Lys Ala Leu

5225 5230 5235

Val Lys Gly Pro Val Tyr Asn Ala Trp Gly Pro Thr Glu Thr Thr

5240 5245 5250

Ile Val Ser Thr Ile Tyr Glu Leu Ala Asp Asp Asp Gln Phe Thr

5255 5260 5265

Asn Gly Val Pro Ile Gly Lys Ala Val Ser Asn Ser Trp Ala Tyr

5270 5275 5280

Val Met Asp Leu Asn Gln Gln Leu Val Pro Val Gly Val Met Gly

5285 5290 5295

Glu Ala Val Val Ile Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp

5300 5305 5310

Pro Ala Leu Asp Cys Asn Arg Phe Val His Ile Thr Ile Asp Gly

5315 5320 5325

Lys Arg Val Arg Ala Tyr Arg Thr Gly Asp Arg Ala Arg Tyr Arg

5330 5335 5340

Pro Lys Asp Gly Glu Ile Glu Phe Phe Gly Arg Met Asp Arg Gln

5345 5350 5355

Leu Lys Ile Arg Gly His Arg Ile Glu Pro Ala Glu Ile Glu His

5360 5365 5370

Ala Met Leu Gly His Asn Asp Ile Val Asp Val Ala Ile Val Thr

5375 5380 5385

Arg His Gln Asp Gly Ala Gly Leu Glu Met Val Ala Phe Val Thr

5390 5395 5400

Ala His Thr Asn Lys Ser Ile Glu Arg Asn Glu Ala Thr Asn Gln

5405 5410 5415

Val Ala Gly Trp Gly Asp His Phe Glu Ser Ser Thr Tyr Ala Glu

5420 5425 5430

Leu Asp Thr Leu Val Lys Ser Asp Val Gly Lys Asp Phe Val Gly

5435 5440 5445

Trp Thr Asn Met Tyr Asp Gly Gly Ala Ile Asp Gln Ala Glu Met

5450 5455 5460

Gln Glu Trp Leu Asp Asp Thr Ile Gln Thr Ile Val Asp Gly Gln

5465 5470 5475

Pro Ala Gly His Val Phe Glu Ile Gly Thr Gly Thr Gly Met Ile

5480 5485 5490

Met Phe Gly Leu Gly Lys Gln Gly Leu Gln Ser Tyr Val Gly Leu

5495 5500 5505

Glu Pro Ser Thr Ser Ala Thr Thr Tyr Val Asn Arg Lys Ile Lys

5510 5515 5520

Thr Ala Pro Thr Val Ala Gly Lys Ala Lys Val Tyr Val Gly Thr

5525 5530 5535

Ala Met Glu Ala Ala Gln Leu Asn Gly Leu His Pro Glu Val Val

5540 5545 5550

Val Ile Asn Ser Val Ala Gln Tyr Phe Pro Thr Pro Glu Tyr Leu

5555 5560 5565

Leu Glu Val Val Gly Ile Leu Thr Gln Met Pro Gly Val Lys Arg

5570 5575 5580

Leu Phe Phe Gly Asp Ile Arg Ser Tyr Ala Thr Asn Arg Lys Phe

5585 5590 5595

Leu Ala Ala Arg Ala Leu His Met Leu Gly Ser Asn Ala Lys Lys

5600 5605 5610

His Asp Ile Arg Arg Lys Met Ala Glu Leu Asp Glu Phe Glu Glu

5615 5620 5625

Glu Leu Ile Val Asp Pro Ser Phe Phe Thr Gly Leu Val Ser Arg

5630 5635 5640

Leu Pro Gly Gln Val Lys His Val Glu Ile Leu Pro Lys Gln Met

5645 5650 5655

Ile Ala Thr Asn Glu Leu Ser Ala Tyr Arg Tyr Ala Ala Val Val

5660 5665 5670

His Leu Ala Leu Pro Glu Glu Gln His Ile Ala Lys Ile Glu Lys

5675 5680 5685

Gly Ala Trp Val Asp Phe Thr Ala Thr Lys Met Asp Arg Ser Ala

5690 5695 5700

Leu Val His His Leu Gln Ser Ser Ser Asn Ala Glu Ile Val Ala

5705 5710 5715

Ile Ser Asn Ile Pro Phe Ser Lys Thr Asn Phe Asp Cys His Leu

5720 5725 5730

Leu Ala Ser Leu Asp Glu Asp Glu Glu His Ser Leu Asp Gly Ser

5735 5740 5745

Ala Trp Ile Lys Thr Ile His Ser Ser Ala Glu Gln Cys Pro Ser

5750 5755 5760

Leu Ser Ala Thr Asp Leu Val Glu Val Ala Lys Glu Val Gly Phe

5765 5770 5775

Arg Val Glu Leu Ser Trp Ala Arg Gln Lys Ser Gln Asn Gly Ala

5780 5785 5790

Leu Asp Ala Ile Phe His Gln Tyr Gln Ser Pro Lys Glu Gly Ser

5795 5800 5805

Arg Val Leu Ile Gln Phe Pro Thr Asp Asp Gln Gly Arg Ser Met

5810 5815 5820

Glu Ser Leu Thr Asn Arg Pro Leu Gln Arg Val Gln Ser Arg Arg

5825 5830 5835

Ile Glu Thr Gln Ile Arg Glu Arg Leu Gln Ala Val Leu Pro Ser

5840 5845 5850

Tyr Met Ile Pro Ala Arg Ile Val Val Leu Asn Glu Met Pro Val

5855 5860 5865

Asn Ala Asn Gly Lys Val Asp Arg Lys Glu Leu Thr Arg Arg Ala

5870 5875 5880

Lys Val Val Pro Arg Ile Glu Thr Ala Ala Glu Arg Ile Gln Pro

5885 5890 5895

Arg Asn Glu Val Glu Ala Val Leu Cys Glu Glu Phe Ser Glu Val

5900 5905 5910

Leu Gly Val Glu Val Gly Val Thr Asp Asn Phe Phe Asp Leu Gly

5915 5920 5925

Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala Arg Thr Gly Arg

5930 5935 5940

Arg Leu Asp Ala Lys Val Ser Val Lys Asp Val Phe Asp His Pro

5945 5950 5955

Val Leu Ala Asp Leu Ala Ala Ala Ile Gln Arg Gly Ser Thr Pro

5960 5965 5970

His Ser Ala Ile Val Thr Thr Glu Tyr Ser Gly Pro Val Glu Gln

5975 5980 5985

Ser Tyr Ala Gln Gly Arg Leu Trp Phe Leu Glu Gln Leu Asn Phe

5990 5995 6000

Lys Ala Thr Trp Tyr Leu Leu Pro Leu Ala Val Arg Ile Arg Gly

6005 6010 6015

Pro Leu Asn Ile Lys Ala Leu Thr Thr Ala Leu His Ala Leu Glu

6020 6025 6030

Gln Arg His Glu Thr Leu Arg Thr Thr Phe Ile Glu Arg Asp Gly

6035 6040 6045

Val Gly Lys Gln Ala Val Gln Pro Phe Gln Pro Lys Glu Leu Glu

6050 6055 6060

Ile Val Asp Ile Ala Ala Asp His Gln Gly Asp Tyr Leu Lys Val

6065 6070 6075

Leu Arg Asp Glu Gln Thr Thr Met Phe Asn Leu Ala Thr Gln Pro

6080 6085 6090

Gly Trp Arg Val Thr Leu His Arg Val Asp Gln Asn Thr His Asn

6095 6100 6105

Leu Ser Ile Val Met His His Ile Ile Ser Asp Gly Trp Ser Val

6110 6115 6120

Asp Val Leu Arg His Glu Leu Arg Gln Phe Tyr Ala Ala Ala Leu

6125 6130 6135

Arg Gly Gln Asp Pro Leu Ala His Ile Ser Pro Leu Pro Ile Gln

6140 6145 6150

Tyr Arg Asp Phe Ser Leu Trp Gln Lys Gln Pro Asp Gln Ile Ile

6155 6160 6165

Glu His Ala Lys Gln Leu Glu Tyr Trp Thr Lys Gln Leu Ala Asp

6170 6175 6180

Ser Ser Pro Ala Glu Leu Pro Thr Asp Leu Pro Arg Pro Ala Val

6185 6190 6195

Leu Ser Gly Lys Ala Gly Glu Val Ala Leu Ser Val Lys Gly Pro

6200 6205 6210

Leu Tyr Glu Arg Leu Gln Ala Phe Cys Lys Thr His Gln Thr Thr

6215 6220 6225

Ala Phe Ala Thr Leu Leu Ala Ala Phe Arg Ala Thr His His Arg

6230 6235 6240

Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr Pro Ile Ala Asn

6245 6250 6255

Arg Asn Arg Pro Glu Leu Glu Asn Leu Ile Gly Phe Phe Val Asn

6260 6265 6270

Ala Gln Cys Met Arg Ile Thr Ile Asp Gly Asp Glu Thr Phe Glu

6275 6280 6285

Ser Leu Ile Arg Gln Val Arg Ala Thr Ala Thr Ala Ala Ile Ala

6290 6295 6300

Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Thr Met Gln Ser

6305 6310 6315

Thr Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu Met Phe

6320 6325 6330

Ala Leu His Ser Gln Gln Asp Leu Gly Lys Ile Gln Leu Glu Gly

6335 6340 6345

Cys Glu Thr Glu Pro Ile Pro Arg Ala Val Arg Thr Arg Phe Asp

6350 6355 6360

Leu Glu Phe His Leu Tyr Gln Glu Gln Gly Ser Leu Gly Gly Ile

6365 6370 6375

Val Tyr Phe Ala Thr Asp Leu Phe Glu Pro Glu Ser Ile Glu Gly

6380 6385 6390

Met Val Ser Ile Phe Lys Glu Ile Leu Ala Arg Ala Leu Asp Gln

6395 6400 6405

Pro Gln Thr Pro Leu Ala Leu Leu Pro Leu Thr Asp Gly Leu Ala

6410 6415 6420

Glu Leu Arg Arg Arg Gly Leu Leu Glu Ile Glu Arg Pro Ser Tyr

6425 6430 6435

Pro Arg Glu Ser Ser Val Val Asp Val Phe Cys Ser Gln Val Ala

6440 6445 6450

Ala Ser Pro Asn Ala Thr Ala Val Lys Asp Ser Ile Ser Gln Leu

6455 6460 6465

Thr Tyr Ala Gln Leu Asn Glu Gln Ser Asp Lys Val Ala Ala Trp

6470 6475 6480

Leu His Gln Cys Asn Leu Pro Thr Glu Thr Leu Val Ala Val Leu

6485 6490 6495

Ala Pro Arg Ser Cys Gln Thr Val Val Ala Phe Leu Gly Ile Leu

6500 6505 6510

Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro Ala

6515 6520 6525

Ala Arg Ile Glu Ala Ile Leu Ser Glu Val Ser Gly His Ile Leu

6530 6535 6540

Val Leu Leu Gly Ser His Val Ser Ala Pro Lys Ile Glu Leu Ala

6545 6550 6555

Asp Val Glu Phe Val Lys Ile Asp Asn Thr Val Glu His Asn Leu

6560 6565 6570

Pro Gly Arg Ile Gly Ser Ala Pro Ser Ala Thr Ser Leu Ala Tyr

6575 6580 6585

Val Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Lys

6590 6595 6600

Val Glu His Arg Gly Ile Val Arg Leu Val Lys Glu Ser Asn Val

6605 6610 6615

Val Ala Lys Met Pro Gln Ala Ala Arg Ile Ala His Leu Ser Asn

6620 6625 6630

Ile Ala Phe Asp Ala Ala Thr Trp Glu Leu Tyr Ala Ala Leu Leu

6635 6640 6645

Asn Gly Gly Thr Leu Val Cys Ile Asn Tyr Leu Thr Thr Leu Asp

6650 6655 6660

Ser Lys Ala Leu Glu Ala Val Phe Glu Gln Glu Lys Ile Gln Ala

6665 6670 6675

Ala Met Leu Pro Pro Ala Leu Leu Lys Gln Tyr Leu Val Asn Ile

6680 6685 6690

Pro Ala Ala Ile Gly Ala Leu Glu Val Val Leu Val Ala Gly Asp

6695 6700 6705

Arg Phe Asp Arg Arg Asp Ala Ala Ala Thr Gln Ala Leu Val Gly

6710 6715 6720

Ala Gly Val Tyr Asn Ala Tyr Gly Pro Thr Glu Asn Thr Thr Leu

6725 6730 6735

Ser Thr Ile Tyr Asn Val Val Gln Gly Asp Ala Asn Val Asn Gly

6740 6745 6750

Val Pro Ile Gly Arg Pro Val Ser Asn Ser Gly Ala Tyr Ile Met

6755 6760 6765

Asn Met Asn Gln Glu Leu Val Pro Ile Gly Val Ile Gly Glu Leu

6770 6775 6780

Val Val Val Gly Asp Gly Val Ala Arg Gly Tyr Thr Asp Pro Ala

6785 6790 6795

Leu Asp Val Asn Arg Phe Val Asn Val Thr Ile Glu Gly Gln Thr

6800 6805 6810

Met Arg Ala Tyr Arg Thr Gly Asp Arg Ala Arg Tyr Arg Pro Lys

6815 6820 6825

Asp Ala Gln Ile Glu Phe Phe Gly Arg Met Asp Gln Gln Ile Lys

6830 6835 6840

Ile Arg Gly His Arg Ile Glu Pro Ala Glu Val Glu His Ala Leu

6845 6850 6855

Leu Asn Asn Asp Leu Leu Gln Asp Ala Ala Val Ile Ile Arg Lys

6860 6865 6870

Gln Gln Asn Asp Glu Leu Glu Met Val Ala Phe Val Glu Ala Asn

6875 6880 6885

Ser Asn Lys Ser Ile Glu Gln Glu Ala Ser Asn Gln Val Glu Asp

6890 6895 6900

Trp Gly Ala Gln Phe Glu Ser Asn Val Tyr Ala Glu Ile Glu Ala

6905 6910 6915

Ile Asp Ala Ser Ala Val Gly Asn Asp Phe Met Gly Trp Thr Ser

6920 6925 6930

Met Tyr Asp Gly Ser Ala Ile Asp Lys Ala Glu Met Gln Glu Trp

6935 6940 6945

Leu Asp Asp Thr Met Gln Thr Ile Leu Asp Gly Arg Pro Ala Gly

6950 6955 6960

Arg Val Leu Glu Ile Gly Thr Gly Thr Gly Met Ile Leu Phe Asn

6965 6970 6975

Leu Gly Glu Gly Leu Gln Ser Tyr Val Gly Leu Glu Pro Ser Thr

6980 6985 6990

Ser Ala Ala Ala Phe Val Asn Arg Arg Ile Gln Thr Leu Pro Ala

6995 7000 7005

Phe Ala Gly Lys Ala Glu Val His Val Gly Thr Ala Thr Asp Ile

7010 7015 7020

Ser Gln Leu Gln Asp Leu Arg Pro Glu Val Val Val Ile Asn Ser

7025 7030 7035

Val Ala Gln Tyr Phe Pro Ser Pro Glu Tyr Leu Ser Lys Val Leu

7040 7045 7050

Tyr Ala Leu Ala Gln Ile Pro Gly Val Lys Arg Leu Phe Phe Gly

7055 7060 7065

Asp Met Arg Ser Tyr Ala Ile Asn Asp Gln Phe Leu Ala Ala Arg

7070 7075 7080

Ala Leu His Asn Ile Gly Ser Lys Ala Thr Lys Ser Ala Ile Arg

7085 7090 7095

Ser Lys Met Val Asp Leu Glu Asn Ser Glu Glu Glu Leu Leu Val

7100 7105 7110

Asp Pro Thr Phe Phe Thr Asn Leu Ala Thr Glu Leu Pro Glu Val

7115 7120 7125

Glu His Val Glu Ile Leu Pro Lys Arg Met Gln Ala Thr Asn Glu

7130 7135 7140

Leu Ser Ala Tyr Arg Tyr Ala Ala Val Val His Ile Arg Asp Pro

7145 7150 7155

Ala Arg Gln Ala Gln Thr Val His Thr Ile Asp Pro Thr Ala Trp

7160 7165 7170

Ile Asp Phe Ser Ala Ser Gln Met Asn Arg Thr Ala Leu Ala Asn

7175 7180 7185

Leu Leu Gln Asn Ser Ala Asp Ala Ala Ala Ile Ala Val Ser Asn

7190 7195 7200

Ile Pro Tyr Ser Lys Thr Ile Leu Ala Arg His Ile Val Gln Ser

7205 7210 7215

Leu Asp Asp Asp Leu Thr Asp Ser Asp Asp Pro Gln Asp Glu Leu

7220 7225 7230

Glu Gly Ala Ala Trp Met Ser Ala Ile Arg Ser Asn Ile Lys Thr

7235 7240 7245

Cys Ala Ser Leu Ser Ala Phe Asp Leu Ala Gln Leu Ala Gln Glu

7250 7255 7260

Lys Gly Phe Arg Val Glu Leu Ser Trp Ala Arg Gln Arg Thr His

7265 7270 7275

His Gly Ala Leu Asp Ala Val Phe His His Tyr Lys Ser Asn Gln

7280 7285 7290

Asp Gly Gly Arg Val Leu Val Gln Phe Pro Thr Asp Ser Arg Pro

7295 7300 7305

Arg Leu Ser Gly Gln Leu Thr Asn Gln Pro Leu Gln Arg Leu Gln

7310 7315 7320

Ser Arg Arg Leu Glu Ala Gln Ile Arg Asp Gln Leu Ser Ala Leu

7325 7330 7335

Leu Pro Ser Tyr Met Ile Pro Ser Leu Ile Val Met Val Asp Glu

7340 7345 7350

Met Pro Leu Asn Ala Asn Gly Lys Val Asp Arg Lys Ala Leu Glu

7355 7360 7365

Arg Arg Ala Arg Met Val Gln Lys Val Glu Lys Pro Ala Ser Glu

7370 7375 7380

Arg Val Gly Ala Arg Asn Glu Ile Glu Ala Ala Leu Cys Glu Val

7385 7390 7395

Phe Val Asp Leu Leu Gly Thr Glu Val Ser Ile Thr Asp Asn Phe

7400 7405 7410

Phe Asn Leu Gly Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala

7415 7420 7425

Arg Ile Ser Arg Arg Leu Asp Ala Arg Ile Ser Val Lys Asp Val

7430 7435 7440

Phe Asp Tyr Pro Val Leu Ala Asp Leu Ala Gly Ala Val Gln Arg

7445 7450 7455

Gly Ser Thr Pro His Asn Pro Ile Val Ala Thr Pro Tyr Ser Gly

7460 7465 7470

Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp

7475 7480 7485

Gln Leu Asn Ala Gly Ser Leu Trp Tyr Ile Gln Pro Ile Ala Val

7490 7495 7500

Arg Val Arg Gly Ser Leu Asn Ile Gly Ala Leu Thr Thr Ala Leu

7505 7510 7515

Asn Ala Leu Glu Lys Arg His Glu Pro Leu Arg Thr Thr Phe Glu

7520 7525 7530

Glu His Asp Gly Ile Gly Val Gln Val Val Gln Pro His Gln Pro

7535 7540 7545

Lys Lys Leu Arg Ile Val Asp Thr Val Ala Asn Tyr Gln Gly Asp

7550 7555 7560

Phe Ile Arg Ala Leu Arg Lys Glu Gln Gln Thr Leu Phe Asn Leu

7565 7570 7575

Ala Thr Glu Pro Gly Trp Arg Val Ser Leu Leu Arg Ile Gly Glu

7580 7585 7590

Asp Asp Asn Ile Leu Ser Ile Val Met His His Ile Ile Ser Asp

7595 7600 7605

Gly Trp Ser Val Asp Ile Leu Arg Gln Asp Leu Lys Leu Phe Tyr

7610 7615 7620

Ala Ala Ala Leu Lys Ser Gln Glu Pro Gln Val Asp Ala Leu Pro

7625 7630 7635

Ile Gln Tyr Arg Asp Phe Ala Phe Trp Gln Lys Gln Pro Glu Gln

7640 7645 7650

Val Ala Glu His Gln Arg Gln Leu Asp Tyr Trp Ile Glu Gln Leu

7655 7660 7665

Lys Asp Ser Lys Pro Ala Glu Leu Ile Thr Asp Phe Pro Arg Pro

7670 7675 7680

Glu Val Leu Ser Gly Thr Ala Gly Ile Val Gln Leu Ala Val Asp

7685 7690 7695

Gly Gln Val Tyr Glu Gly Leu Arg Ala Phe Cys Arg Ile His Gln

7700 7705 7710

Thr Thr Ser Phe Val Val Leu Leu Ala Ala Phe Arg Ala Ala His

7715 7720 7725

Tyr Arg Leu Thr Gly Thr Glu Asp Ala Thr Ile Gly Ser Pro Ile

7730 7735 7740

Ala Asn Arg Asn Arg Pro Glu Leu Glu Ser Leu Ile Gly Phe Phe

7745 7750 7755

Val Asn Thr Gln Cys Met Arg Ile Met Val Gly Glu Asp Asp Thr

7760 7765 7770

Phe Glu Arg Leu Val Gln Gln Val Arg Ser Thr Thr Thr Ala Ala

7775 7780 7785

Phe Ala Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Ser Val

7790 7795 7800

Gln Ser Thr Ser Arg Asp Ala Ser Arg Asn Pro Leu Val Gln Leu

7805 7810 7815

Met Phe Ala Leu His Ser Gln Gln Gly Ile Gly Leu Met Glu Leu

7820 7825 7830

Glu Gly Val Glu Thr Glu Pro Ile Ala Arg Asp Val Ser Thr Arg

7835 7840 7845

Phe Asp Ile Glu Phe His Leu Tyr Gln Lys Glu Glu Ser Leu His

7850 7855 7860

Gly Val Val His Phe Ala Ala Asp Leu Phe Glu Pro Glu Thr Ile

7865 7870 7875

Gln Gly Leu Val Ser Val Phe Gln Glu Ile Leu Arg Arg Gly Leu

7880 7885 7890

Glu Thr Pro Arg Leu Pro Ile Ser Ile Leu Pro Leu Asp Asn Asn

7895 7900 7905

Ile Pro Glu Leu Leu Val Gly Met Leu Asp Val Asp Thr Pro Glu

7910 7915 7920

Tyr Pro Arg Asp Ser Ser Val Val Asp Val Phe Arg Thr Gln Val

7925 7930 7935

Ala Ala Ser Pro Asp Ala Ile Ala Val Lys Asp Ser Thr Ser Gln

7940 7945 7950

Leu Thr Tyr Ala Gln Leu Asp Glu Glu Ser Asn Lys Val Ala Thr

7955 7960 7965

Trp Leu Ser Gln Arg Gln Leu Ala Pro Glu Thr Leu Val Gly Val

7970 7975 7980

Leu Ala Pro Arg Ser Cys Pro Thr Ile Val Thr Phe Phe Gly Ile

7985 7990 7995

Leu Lys Ala Ser Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro

8000 8005 8010

Ser Ala Arg Ile Glu Ala Ile Leu Ser Ala Val Pro Asp His Lys

8015 8020 8025

Leu Val Phe Leu Gly Ala Asp Val Pro Asp Pro Glu Ala Pro Leu

8030 8035 8040

Val Asn Val Glu Leu Val Arg Ile Asp Asp Ile Leu Arg Gln Ser

8045 8050 8055

Ile His Ala Ser Asn Ala Gly Leu Leu Ala Asn His Pro Leu Ala

8060 8065 8070

Thr Ser Leu Ala Tyr Val Met Phe Thr Ser Gly Ser Thr Gly Lys

8075 8080 8085

Pro Lys Gly Val Met Val Glu His Arg Ser Ile Val Arg Leu Val

8090 8095 8100

Lys Glu Thr Asn Leu Val Pro Ala Val Glu Ala Val Ser Ser Val

8105 8110 8115

Ala His Ile Ser Asn Val Ala Phe Asp Ala Ala Thr Trp Glu Ile

8120 8125 8130

Tyr Ala Ala Leu Leu Asn Gly Gly Thr Thr Val Cys Ile Asp His

8135 8140 8145

Ile Thr Val Leu Asp Pro Ala Lys Leu Ala Leu Val Phe Ser Ser

8150 8155 8160

Glu Lys Ile Lys Ala Ala Phe Phe Ser Thr Ala Leu Leu Lys Gln

8165 8170 8175

Arg Leu Tyr Glu Glu Pro Ser Thr Ile Thr Gly Leu Asp Leu Leu

8180 8185 8190

Tyr Ala Gly Gly Glu Arg Met Arg Pro Gln Asp Ala Leu Lys Thr

8195 8200 8205

Arg Glu Leu Val Arg Gly Ser Phe Cys His Val Tyr Gly Pro Thr

8210 8215 8220

Glu Asn Thr Thr Phe Ser Thr Val Tyr Pro Met Gly Val Glu Glu

8225 8230 8235

Arg Cys Val Asn Gly Leu Pro Ile Gly Arg Ala Val Ser His Ser

8240 8245 8250

Gly Ala Val Ile Met Asp Ala Asn Gln Arg Leu Val Pro Leu Gly

8255 8260 8265

Val Met Gly Glu Leu Val Val Thr Gly Asp Gly Leu Ala Arg Gly

8270 8275 8280

Tyr Thr Asp Pro Ala Leu Asn Arg Asp Arg Phe Val Glu Val Asn

8285 8290 8295

Ile His Gly Gln Val Leu Arg Ala Tyr Arg Thr Gly Asp Gln Ala

8300 8305 8310

Arg Tyr Arg Pro Lys Asp Gly Gln Ile Glu Phe Ser Gly Arg Met

8315 8320 8325

Asp Arg Gln Leu Lys Ile Arg Gly His Arg Ile Glu Pro Ala Glu

8330 8335 8340

Val Glu His Ala Ile Leu Ser His Asp Asp Ile Arg Asn Ala Val

8345 8350 8355

Val Val Thr Arg Gln Gln Glu Gly Gln Asp Leu Glu Met Val Ala

8360 8365 8370

Phe Val Ser Thr Pro Asn Asp Gln Thr Val Glu Arg Asp Glu Ala

8375 8380 8385

Arg Asn Gln Val Glu Asp Trp Gly Ala Gln Phe Glu Ser Asn Val

8390 8395 8400

Tyr Ala Glu Ile Glu Glu Ile Asp Ser Ser Ala Val Gly Asn Asp

8405 8410 8415

Phe Met Gly Trp Thr Ser Met Tyr Asp Gly Thr Ala Ile Asp Lys

8420 8425 8430

Ala Glu Met Gln Glu Trp Leu Asp Asp Thr Met Arg Thr Leu His

8435 8440 8445

Asp Gly Arg Asp Pro Gly His Val Leu Glu Val Gly Thr Gly Thr

8450 8455 8460

Gly Met Ile Leu Phe Asn Leu Gly Lys Gly Leu Gln Ser Tyr Val

8465 8470 8475

Gly Leu Glu Pro Ser Thr Ser Ala Ala Ala Phe Val Asn Arg Lys

8480 8485 8490

Ile Glu Thr Ile Ser Ser Leu Ala Gly Lys Ala Lys Val Glu Ile

8495 8500 8505

Gly Thr Ala Thr Asp Val Gly Gln Leu Lys Asn Leu Arg Ser Asp

8510 8515 8520

Leu Val Val Ile Asn Ser Val Ala Gln Tyr Phe Pro Ser Pro Glu

8525 8530 8535

Tyr Leu Val Glu Ala Val Thr Ala Leu Val His Ile Pro Gly Val

8540 8545 8550

Lys Arg Leu Phe Phe Gly Asp Met Arg Ser Tyr Ala Met Asn Lys

8555 8560 8565

Gln Phe Leu Val Ala Arg Ala Leu Arg Thr Leu Gly Ala Lys Ala

8570 8575 8580

Asn Lys Asp Asp Val Arg Arg Lys Met Val Glu Leu Glu Glu Phe

8585 8590 8595

Glu Glu Glu Leu Leu Val Asp Pro Ala Phe Phe Thr Gly Leu Ala

8600 8605 8610

Asn Trp Leu Ser Glu Val Glu His Val Glu Ile Leu Pro Lys Gln

8615 8620 8625

Met Thr Ser Thr Asn Glu Leu Ser Ser Tyr Arg Tyr Ala Ala Ile

8630 8635 8640

Val His Leu Arg Leu Pro Gly Gln Glu Ala Gln Pro Val Val Thr

8645 8650 8655

Val Asn Gln Asp Ala Trp Val Asp Phe Gly Gly Ser Lys Met Asp

8660 8665 8670

Arg His Ala Leu Leu His His Leu Gln Ser Ser Pro Lys Ala Glu

8675 8680 8685

Thr Val Ala Ile Ser Asn Ile Pro Tyr Ser Lys Thr Ile Tyr Glu

8690 8695 8700

Arg His Val Leu Ala Ser Leu Asp Asp Asp Glu Val Glu Asp Ser

8705 8710 8715

Leu Asp Gly Ser Ala Trp Leu Ser Ala Val Arg Ser Thr Ala Glu

8720 8725 8730

Gln Cys Ala Ser Leu Ser Gly Val Asp Leu Val Gln Ile Ala Lys

8735 8740 8745

Glu Ala Gly Phe Arg Val Glu Leu Ser Trp Ala Arg Gln Arg Ser

8750 8755 8760

Gln Lys Gly Gly Ile Asp Ala Val Phe His His Tyr Glu Ser Val

8765 8770 8775

His Asp Gly Ala Arg Val Met Val Lys Phe Pro Thr Asp Asp Gln

8780 8785 8790

Gly Arg Ala Leu Asp Ser Leu Ala Asn Arg Pro Leu Gln Arg Leu

8795 8800 8805

Gln Ser Arg Arg Ile Glu Val Gln Ile Arg Glu Arg Leu Gln Ala

8810 8815 8820

Val Leu Pro Ser Tyr Met Met Pro Val Arg Ile Val Val Leu Asp

8825 8830 8835

Glu Met Pro Met Asn Ala Asn Gly Lys Val Asp Arg Lys Val Leu

8840 8845 8850

Thr Arg Arg Ala Lys Met Ile Ser Arg Val Glu Thr Thr Ala Glu

8855 8860 8865

Arg Val Gly Pro Arg Asn Glu Ile Glu Ala Leu Leu Cys Glu Glu

8870 8875 8880

Phe Ala Glu Val Leu Gly Val Glu Val Gly Ile Asn Asp Asp Phe

8885 8890 8895

Phe Asp Leu Gly Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala

8900 8905 8910

Arg Ser Ser Arg Arg Phe Asp Ala Lys Val Ser Val Lys Asp Val

8915 8920 8925

Phe Asp His Pro Ile Leu Ala Asp Leu Ala Ala Ser Ile Gln Arg

8930 8935 8940

Gly Ser Thr Pro His Asn Pro Ile Leu Ala Thr Gln Tyr Ser Gly

8945 8950 8955

Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Glu

8960 8965 8970

Gln Leu Asn Val Ser Ser Thr Trp Tyr Leu Gln Pro Ile Ala Val

8975 8980 8985

Arg Met Arg Gly Pro Leu Lys Ile Glu Ala Leu Ala Ala Ala Phe

8990 8995 9000

His Ala Leu Glu Glu Arg His Glu Thr Leu Arg Thr Thr Phe Glu

9005 9010 9015

Glu His Asp Gly Ile Gly Met Gln Val Val Gln Pro His Arg Pro

9020 9025 9030

Lys Glu Leu Arg Val Ile Asp Val Gln Ala Glu His Asp Gly Asp

9035 9040 9045

Tyr Thr Gln Ala Leu His Thr Glu Gln Thr Thr Thr Phe Asn Leu

9050 9055 9060

Glu Thr Glu Pro Gly Trp Arg Val Ser Val Phe Arg Leu Asn Glu

9065 9070 9075

Asp Asp Asn Ile Leu Ser Ile Val Met His His Ile Ile Ser Asp

9080 9085 9090

Gly Trp Ser Phe Asp Ile Leu Arg Lys Glu Ile Arg Glu Phe Tyr

9095 9100 9105

Asn Ala Ala Leu Lys Gly Lys Asp Pro Leu Ala Gln Met Ser Pro

9110 9115 9120

Leu His Ile Gln Tyr Arg Asp Phe Ser Val Trp Gln Lys Gln Leu

9125 9130 9135

Asn Gln Ile Thr Glu His Lys Arg Gln Leu Asp Tyr Trp Thr Lys

9140 9145 9150

Asn Leu Ala Asp Asn Thr Pro Ala Glu Leu Pro Thr Asp Leu Pro

9155 9160 9165

Arg Pro Ala Val Leu Ser Gly Lys Ala Gly Val Ile Gln Leu Ser

9170 9175 9180

Ile Thr Gly Pro Val Tyr Asp Arg Leu Arg Ala Phe Cys Arg Val

9185 9190 9195

His Gln Thr Thr Leu Phe Thr Val Leu Leu Thr Val Phe Arg Ala

9200 9205 9210

Thr His Tyr Arg Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr

9215 9220 9225

Pro Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Leu Ile Gly

9230 9235 9240

Phe Phe Val Asn Thr Gln Cys Met Arg Ile Thr Val Glu Glu Glu

9245 9250 9255

Asp Thr Phe Glu Thr Leu Ile His Gln Val Arg Thr Thr Thr Thr

9260 9265 9270

Ala Ala Phe Ala Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser

9275 9280 9285

Ala Leu Leu Pro Gly Ser Arg Asp Thr Ser Arg Asn Pro Leu Ser

9290 9295 9300

Gln Ile Met Phe Ala Val His Ser Gln Lys Asn Ile Ser Lys Ile

9305 9310 9315

Glu Leu Asp Gly Leu Glu Ser Glu Ala Ile Ser Arg Ala Thr Ser

9320 9325 9330

Thr Arg Phe Asp Leu Glu Phe His Leu Phe Gln Glu Glu Lys Gly

9335 9340 9345

Leu Gly Gly Ile Val Leu Phe Ala Ala Asp Leu Phe Glu Pro Glu

9350 9355 9360

Thr Ile Asp Ser Leu Val Phe Val Phe Gln Glu Ile Leu Arg Gln

9365 9370 9375

Ser Leu Glu Thr Pro Lys Thr Pro Ile Ala Val Leu Pro Leu Thr

9380 9385 9390

Asn Gly Ile Ala Gln Leu Arg Ser Met Cys Val Leu Asp Ile Glu

9395 9400 9405

Lys Thr Ala Tyr Pro Gln Asp Ser Ser Val Ile Asp Ile Phe Arg

9410 9415 9420

Gln Gln Val Ala Ala Arg Pro Asp Ala Thr Ala Val Thr Asp Ser

9425 9430 9435

Thr Ser Gln Leu Thr Tyr Ala Gln Leu Asp Leu His Ser Asp Glu

9440 9445 9450

Leu Ala Ser Trp Leu Arg Gln Lys Lys Met Ala Pro Glu Thr Leu

9455 9460 9465

Val Gly Val Leu Ala Pro Arg Ser Cys Gln Thr Ile Val Thr Phe

9470 9475 9480

Leu Gly Ile Leu Lys Ala Ser Leu Ala Tyr Leu Pro Leu Asp Val

9485 9490 9495

Lys Val Pro Val Ala Arg Ile Glu Ala Ile Leu Ser Ser Ile Ser

9500 9505 9510

Gly Gln Lys Leu Ile Leu Leu Gly Gln Asp Val Pro Val Pro Glu

9515 9520 9525

Ile Gln Leu Pro Asp Val Asp Val Val Pro Ile Ser Glu Ile Leu

9530 9535 9540

Gly Arg Ser Val Pro Ser Arg Ala Thr Asp Lys Ser Leu Gly Pro

9545 9550 9555

Leu Ala Arg Asn Leu Ala Tyr Val Leu Phe Thr Ser Gly Ser Thr

9560 9565 9570

Gly Lys Pro Lys Gly Val Met Ile Glu His Arg Ser Ile Val Arg

9575 9580 9585

Leu Val Lys Glu Thr Asn Leu Ile Ser Lys Leu Pro Asn Ala Pro

9590 9595 9600

Arg Thr Ala His Leu Thr Asn Leu Val Phe Asp Asn Ser Ala Trp

9605 9610 9615

Glu Ile Tyr Ser Thr Leu Leu Asn Gly Gly Thr Leu Val Cys Ile

9620 9625 9630

Asp Tyr Ala Thr Val Leu Asp Ser Lys Ala Leu Glu Thr Val Phe

9635 9640 9645

Lys Glu Gln Arg Ile Gln Thr Ser Leu Met Pro Pro Ala Leu Leu

9650 9655 9660

Lys Glu Cys Leu Ala Asn Met Pro Thr Met Phe Asp Asp Val Glu

9665 9670 9675

Val Leu Tyr Ala Leu Gly Asp Arg Phe Asp Lys Gln Asp Ala Met

9680 9685 9690

Lys Ala Arg Ser Ile Val Lys Thr Ala Val Tyr Asn Ala Tyr Gly

9695 9700 9705

Pro Thr Glu Asn Thr Val Ile Ser Thr Ile Tyr Glu Ile Ala Lys

9710 9715 9720

Asp Asp Ser Phe Val Asn Gly Val Pro Ile Gly Arg Ser Ile Ser

9725 9730 9735

Asn Ser Gly Ala Phe Ile Met Asp Ser Arg Gln Gln Leu Val Pro

9740 9745 9750

Val Gly Val Leu Gly Glu Leu Val Val Ser Gly Asp Gly Leu Ala

9755 9760 9765

Arg Gly Tyr Thr Asp Pro Thr Leu Asp Val Asn Arg Phe Val Glu

9770 9775 9780

Val Thr Val Asp Gly Gln His Val Arg Val Tyr Arg Thr Gly Asp

9785 9790 9795

Arg Val Arg Phe Arg Pro Lys Asp Gly Gln Ile Glu Phe Phe Ser

9800 9805 9810

Arg Met Asp Gln Gln Val Lys Ile Arg Gly His Arg Ile Glu Pro

9815 9820 9825

Ala Glu Val Glu His Val Ile Leu Thr Asn Lys Ile Ile Arg Asp

9830 9835 9840

Ala Ala Val Ala Ile Arg Arg Pro Glu Gly Gln Glu Pro Glu Met

9845 9850 9855

Val Ala Phe Val Thr Thr His Glu Asn Thr Ser Ile Glu Lys Gln

9860 9865 9870

Ser Val Glu Glu Phe Ala Ala Arg Ile Glu Asn Glu Val Arg Arg

9875 9880 9885

Trp Ile Lys Thr Leu Leu Pro Leu Tyr Met Val Pro Thr Gln Ile

9890 9895 9900

Val Val Leu Asp Arg Met Pro Val Asn Ala Asn Gly Lys Val Asp

9905 9910 9915

Arg Lys Glu Leu Ala Gln Arg Ala Gln Thr Leu Gln Lys Ser Glu

9920 9925 9930

Ala Gly Ser Leu Pro Ser Val Arg Val Pro Pro Thr Asn Asp Met

9935 9940 9945

Glu Arg Ile Leu Cys Glu Glu Phe Ala Asp Val Leu Gly Val Glu

9950 9955 9960

Val Gly Ile Thr Asp Asn Phe Phe Asp Phe Gly Gly His Ser Leu

9965 9970 9975

Met Ala Thr Lys Leu Ala Ala Arg Ile Ser Arg Arg Val Asn Ala

9980 9985 9990

Arg Val Ser Val Lys Ser Val Phe Asp His Pro Val Leu Val Asp

9995 10000 10005

Leu Ala Ser Thr Ile Lys Gln Asp Ser Ile Met His Lys Pro Ile

10010 10015 10020

Pro Gln Thr Ala Tyr Thr Gly Pro Val Glu Gln Ser Phe Ala Gln

10025 10030 10035

Gly Arg Leu Trp Phe Leu Asp Gln Leu Asn Phe Gly Ala Ser Trp

10040 10045 10050

Tyr Leu Met Pro Leu Ala Leu Arg Leu Gln Gly Ser Leu His Val

10055 10060 10065

Lys Ser Leu Thr Thr Ala Leu Phe Ala Leu Glu Gln Arg His Glu

10070 10075 10080

Thr Leu Arg Thr Thr Phe Glu Glu Gln Asp Gly Val Gly Ile Gln

10085 10090 10095

Ile Val His Pro Ala Asn Lys Lys Asp Leu Arg Ile Leu Asp Val

10100 10105 10110

Ser Lys Glu Gln Asn Ser Asp Tyr Ala Lys Val Leu His Lys Glu

10115 10120 10125

Arg Thr Ile Pro Ile Asp Leu Thr Ser Glu Pro Gly Trp Arg Val

10130 10135 10140

Ser Leu Ile Arg Leu Gly Glu Asp Asp His Ile Leu Ser Ile Val

10145 10150 10155

Met His His Ile Ile Ser Asp Gly Trp Ser Val Asp Val Leu Arg

10160 10165 10170

Gln Glu Leu Lys Gln Phe Tyr Thr Ala Ala Leu Lys Gly Gln Asp

10175 10180 10185

Pro Leu Ala Gln Ile Asp Ala Leu Pro Ile Gln Tyr Arg Asp Phe

10190 10195 10200

Ser Leu Trp Gln Lys Leu Pro Asp Gln Val Ala Glu His Gln Arg

10205 10210 10215

Gln Leu Glu Tyr Trp Ala Glu Gln Leu Ala Asp Asn Thr Pro Ala

10220 10225 10230

Glu Leu Leu Thr Asp Leu Pro Arg Pro Asp Val Leu Ser Gly Lys

10235 10240 10245

Ala Gly Ala Val Gln Leu Thr Ile Asp Gly Pro Val Phe Asp Gln

10250 10255 10260

Leu Gln Ala Phe Cys Arg Ala His Gln Thr Thr Met Phe Thr Val

10265 10270 10275

Leu Leu Ala Val Phe Arg Thr Thr His Tyr Arg Leu Thr Gly Ala

10280 10285 10290

Thr Asp Ala Thr Ile Gly Thr Pro Ile Ala Asn Arg Asn Arg Pro

10295 10300 10305

Glu Leu Glu Arg Leu Val Gly Phe Phe Val Asn Thr Gln Cys Ile

10310 10315 10320

Arg Ile Thr Val Asp Val Glu Asp Thr Phe Glu Ala Leu Val Arg

10325 10330 10335

Gln Val His Ser Thr Ser Thr Thr Ala Phe Ala Asn Gln Asp Val

10340 10345 10350

Pro Phe Glu Arg Ile Val Ser Thr Ile Leu Pro Gly Ser Arg Asp

10355 10360 10365

Ala Ser Arg Asn Pro Leu Ala Gln Leu Met Phe Ala Val His Ser

10370 10375 10380

Gln Arg Asp Ile Ser Lys Phe Gln Leu Glu Gly Leu Asp Thr Lys

10385 10390 10395

Pro Ile Pro Thr Ala Ala Ser Thr Arg Phe Asp Ile Glu Phe His

10400 10405 10410

Met Phe Gln Gln Ala Glu Arg Leu Ser Gly Arg Val Leu Phe Ala

10415 10420 10425

Glu Asp Leu Phe Glu Leu Glu Thr Ile Gln Gly Met Val Val Ile

10430 10435 10440

Phe Lys Glu Ile Leu Arg Arg Gly Leu Glu Thr Pro Gln Thr Pro

10445 10450 10455

Leu Ala Val Leu Pro Leu Thr Asp Gly Leu Ala His Leu Arg Ser

10460 10465 10470

Gln Gly Leu Leu Glu Ile Glu Arg Pro Glu Tyr Pro Arg Asp Ser

10475 10480 10485

Ser Met Ile Asp Val Phe Arg Ala Gln Val Ala Ala Cys Pro Asp

10490 10495 10500

Ala Ile Ala Val Lys Asp Ser Thr Ser Gln Leu Thr Tyr Ser Gln

10505 10510 10515

Leu Asp Asp Gln Ser Asp Lys Ile Thr Ala Trp Leu Leu Gln Arg

10520 10525 10530

Lys Ile Pro Ala Glu Ser Leu Val Ala Val Tyr Ala Pro Arg Thr

10535 10540 10545

Cys Gln Thr Ile Ile Thr Phe Phe Gly Ile Leu Lys Ala Asn Leu

10550 10555 10560

Ala Tyr Leu Pro Leu Asp Ile Asn Val Pro Ala Ala Arg Ile Glu

10565 10570 10575

Ala Ile Leu Ser Thr Ile Ser Gly His Lys Leu Val Leu Leu Gly

10580 10585 10590

Ser Gln Val Ser Ala Pro Ala Val Gln Leu Lys Asp Val Glu Tyr

10595 10600 10605

Val Trp Ile Asp Glu Ala Met Ala Glu Thr Val Arg Thr Cys Thr

10610 10615 10620

Ser Pro Glu Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr

10625 10630 10635

Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Lys Val Glu His Arg

10640 10645 10650

Gly Val Val Arg Leu Val Lys Gln Ser Asn Val Val Ala Lys Met

10655 10660 10665

Pro Gln Ala Ala Arg Val Ala His Leu Ser Asn Ile Ala Phe Asp

10670 10675 10680

Ala Ala Thr Trp Glu Ile Tyr Ala Ala Leu Leu Asn Gly Gly Ser

10685 10690 10695

Leu Ile Cys Ile Asp Tyr Phe Thr Thr Leu Asp Ser Lys Glu Leu

10700 10705 10710

Glu Ala Val Phe Ala Arg Glu Lys Ile Gln Ala Ala Met Leu Pro

10715 10720 10725

Pro Ala Leu Leu Lys Gln Cys Leu Val Asn Ile Pro Ala Thr Ile

10730 10735 10740

Ser Ala Leu Asp Val Val Leu Ala Ala Gly Asp Arg Phe Asp Arg

10745 10750 10755

Arg Asp Ala Ala Ala Thr Gln Ala Leu Val Gly Gly Cys Val Tyr

10760 10765 10770

Asn Ala Tyr Gly Pro Thr Glu Asn Thr Thr Leu Ser Thr Ile Tyr

10775 10780 10785

Asn Val Val Lys Gly Asp Ala Asn Val Asn Gly Val Pro Ile Gly

10790 10795 10800

Arg Pro Val Ser Asn Ser Gly Ala Tyr Ile Met Asp Pro Asn Gln

10805 10810 10815

Gln Leu Val Pro Lys Gly Val Met Gly Glu Leu Ile Val Val Gly

10820 10825 10830

Asp Gly Val Ala Arg Gly Tyr Thr Asp Pro Ala Leu Asp Val Asn

10835 10840 10845

Arg Phe Ile Glu Ile Ala Ile Asp Gly Asp Gln Ala Val Arg Ala

10850 10855 10860

Tyr Arg Thr Gly Asp Arg Ala Arg Tyr Arg Pro Lys Asp Gly Gln

10865 10870 10875

Ile Glu Phe Phe Gly Arg Met Asp Gln Gln Ile Lys Ile Arg Gly

10880 10885 10890

His Arg Ile Glu Pro Ala Glu Val Glu His Ala Val Leu Asp Asn

10895 10900 10905

Ser Met Val Gln Asp Ala Ala Val Ile Thr Arg Lys Gln Asp Gln

10910 10915 10920

Glu Leu Glu Met Ile Ala Phe Val Thr Thr Arg Ser Asp Lys Glu

10925 10930 10935

Ile Asp Asn Asp Glu Ala Ser Asn Gln Val Glu Asp Trp Gly Asn

10940 10945 10950

Gln Phe Glu Ser Asn Ile Tyr Ala Glu Ile Glu Glu Ile Asp Ser

10955 10960 10965

Ser Ala Ile Gly Lys Asp Phe Met Gly Trp Thr Ser Met Tyr Asp

10970 10975 10980

Gly Ser Ala Ile Asp Lys Asp Glu Met Gln Glu Trp Leu Asp Asp

10985 10990 10995

Thr Met Ser Thr Leu Leu Asp Gly Arg Gln Pro Gly His Val Leu

11000 11005 11010

Glu Ile Gly Thr Gly Thr Gly Met Ile Leu Phe Asn Leu Ala Glu

11015 11020 11025

Arg Met Gly Leu Lys Ser Tyr Val Gly Leu Asp Pro Ser Glu Lys

11030 11035 11040

Ala Thr Ser Phe Val Lys Gln Ala Ile Lys Ser Arg Pro Ser Leu

11045 11050 11055

Ala Gly Lys Ala Glu Val His Val Gly Thr Ala Thr Asp Val Ala

11060 11065 11070

Arg Met Arg Asp Leu His Pro Glu Val Val Val Ile Asn Ser Val

11075 11080 11085

Ala Gln Tyr Phe Pro Ser Pro Glu Tyr Leu Ala Asp Val Val Gly

11090 11095 11100

Ala Leu Val Arg Ile Pro Gly Val Lys Arg Leu Phe Phe Gly Asp

11105 11110 11115

Ile Arg Ser Tyr Ala Thr Asn Asn His Phe Leu Ala Ala Arg Ala

11120 11125 11130

Leu His Lys Leu Gly Glu Lys Ala Thr Arg Asp Thr Val Arg Ser

11135 11140 11145

Lys Met Ala Glu Leu Glu Gly Tyr Glu Glu Glu Leu Leu Val Asp

11150 11155 11160

Pro Thr Phe Phe Thr Ser Leu Thr Ala Lys Leu His Gly Gln Val

11165 11170 11175

Glu His Val Glu Ile Leu Pro Lys Arg Met Gln Ala Thr Asn Glu

11180 11185 11190

Leu Ser Ala Tyr Arg Tyr Ala Ala Ile Val Tyr Ile Arg Asp Pro

11195 11200 11205

Lys Arg Ala Gln Thr Val Gln Thr Val Lys Ser Asp Ala Trp Val

11210 11215 11220

Asp Phe Ser Thr Ser Gln Met Asp Arg Ser Val Leu Val Ser Leu

11225 11230 11235

Leu Gln Ser Ser Asp Ala Glu Ala Ile Ala Val Ser Asn Ile Pro

11240 11245 11250

Tyr Ser Lys Thr Ile Val Ala Arg His Ile Val Glu Ser Leu Ser

11255 11260 11265

Ala Glu Asp Ser Gln Glu Met Leu Asp Gly Pro Ala Trp Ile Ser

11270 11275 11280

Ala Val Arg Ser Ser Ala Glu Gln Cys Ala Ser Leu Ser Ala Ile

11285 11290 11295

Asp Leu Val Gln Val Ala Lys Glu Asn Gly Phe Arg Val Glu Leu

11300 11305 11310

Ser Cys Ala Arg Gln Arg Ser His Asn Gly Ala Ile Asp Ala Val

11315 11320 11325

Phe His His Tyr Lys Pro Ala Gln Glu Gly Ser Arg Val Leu Leu

11330 11335 11340

Gln Phe Pro Thr Asp Asn His Ile Arg Ala Gly Ser Leu Thr Asn

11345 11350 11355

Arg Pro Leu Gln Arg Leu Glu Ser Arg Arg Val Glu Thr Lys Leu

11360 11365 11370

Lys Glu His Leu Phe Ser Val Leu Pro Ser Tyr Met Ile Pro Ser

11375 11380 11385

His Ile Val Met Val Asp Gln Met Pro Leu Asn Ala Asn Gly Lys

11390 11395 11400

Val Asp Arg Lys Ala Leu Ala Gln Arg Ala Glu Ala Val Leu Lys

11405 11410 11415

Ile Glu Lys Pro Ala Ser Glu Arg Val Ser Ala Arg Asn Glu Val

11420 11425 11430

Glu Ala Val Leu Cys Glu Glu Phe Thr Asp Val Leu Gly Val Glu

11435 11440 11445

Val Gly Ile Thr Asp Asn Phe Phe Asp Leu Gly Gly His Ser Leu

11450 11455 11460

Met Ala Thr Lys Leu Ala Ala Arg Ile Ser Lys His Leu Asp Ala

11465 11470 11475

Arg Val Ser Val Lys Asp Val Phe Asp Tyr Pro Val Val Ala Asp

11480 11485 11490

Leu Ala Ala Ser Ile Glu Arg Asn Ser Ile Pro His Asn Pro Ile

11495 11500 11505

Pro Ser Thr Asn Tyr Ser Gly Pro Val Glu Gln Ser Phe Ala Gln

11510 11515 11520

Gly Arg Leu Trp Phe Leu Asp Gln Leu Asn Met Gly Val Ser Glu

11525 11530 11535

Leu Tyr Leu Met Pro Leu Ala Leu Arg Leu Arg Gly Pro Leu Arg

11540 11545 11550

Val Asp Ala Phe Ala Ala Ala Val Ser Ala Leu Glu Ala Arg His

11555 11560 11565

Glu Thr Leu Arg Thr Thr Phe Met Asp His Asp Gly Val Gly Met

11570 11575 11580

Gln Val Ile Leu Pro Ser Asn Ser Lys Lys Leu Arg Val Ile Asp

11585 11590 11595

Ala Ser Glu Asn Asp Tyr Ile Asp Ile Leu Arg Gln Glu Arg Thr

11600 11605 11610

Ala Pro Phe Asn Leu Thr Thr Glu Pro Gly Phe Arg Ile Ala Leu

11615 11620 11625

Leu Gln Leu Gly Gln Thr Asp Phe Ile Leu Ser Ile Val Met His

11630 11635 11640

His Ile Ile Tyr Asp Gly Trp Ser Ile Asp Val Leu Cys Arg Glu

11645 11650 11655

Leu Gly Arg Phe Tyr Ser Ala Ala Leu Gln Gly Gln Asp Pro Leu

11660 11665 11670

Ala Gln Val Ser Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ser Ile

11675 11680 11685

Trp Gln Lys Arg Pro Glu Gln Val Ala Glu His Glu Arg Gln Leu

11690 11695 11700

Gln Tyr Trp Thr Glu Gln Leu Ala Asp Ser Ser Pro Ala Glu Leu

11705 11710 11715

Leu Thr Asp Leu Pro Arg Pro Leu Val Pro Thr Gly Lys Ala Gly

11720 11725 11730

Ile Val Gln Leu Thr Ile Glu Gly Ala Val Tyr Glu Arg Leu Arg

11735 11740 11745

Ala Phe Cys Arg Val His Gln Thr Thr Ser Phe Ala Val Leu Leu

11750 11755 11760

Ala Ala Phe Arg Ala Thr His Tyr Arg Leu Thr Gly Ala Glu Asp

11765 11770 11775

Ala Thr Ile Gly Ser Pro Ile Ala Asn Arg Asn Arg Pro Glu Leu

11780 11785 11790

Glu Ser Leu Ile Gly Phe Phe Val Asn Thr Gln Cys Ile Arg Val

11795 11800 11805

Thr Ile Arg Glu Asp Asp Thr Phe Asp Lys Leu Val Gln Gln Val

11810 11815 11820

Arg Ala Thr Thr Thr Ala Ala Gln Val Asn Gln Asp Val Pro Phe

11825 11830 11835

Glu Arg Ile Val Ser Ala Leu Met Pro Gly Ser Arg Asp Thr Ser

11840 11845 11850

Arg Asn Pro Leu Val Gln Leu Ser Phe Ala Leu His Ser Gln His

11855 11860 11865

Asp Leu Gly Arg Ile Asp Leu Gln Asp Leu Thr Gly Glu Ala Leu

11870 11875 11880

Pro Thr Pro Val Phe Thr Arg Leu Asp Val Glu Phe His Leu Phe

11885 11890 11895

Gln Gln Ala Glu Lys Phe Gly Gly Ser Val Leu Phe Ala Thr Asp

11900 11905 11910

Leu Phe Glu Pro Glu Thr Ile Gln Gly Leu Val Ser Val Phe Gln

11915 11920 11925

Glu Val Leu Arg Arg Gly Leu Glu Gln Pro Gln Thr Pro Ile Ala

11930 11935 11940

Val Leu Pro Leu Asp Asn Ala Ser Glu Asp Leu Arg Ser Met Gly

11945 11950 11955

Leu Leu Gln Met Glu Arg Thr Asn Tyr Pro Arg Asp Ser Ser Val

11960 11965 11970

Val Asp Val Phe Arg Asp Gln Val Ala Ala Asn Pro Arg Ala Ile

11975 11980 11985

Ala Val Lys Asp Ser Val Leu Glu Leu Thr Tyr Ala Gln Leu Asp

11990 11995 12000

Glu Lys Ser Asp Gln Leu Ala Ala Trp Leu Cys Gln His Asn Ile

12005 12010 12015

Pro Ala Glu Thr Ile Val Gly Val Leu Ala Pro Arg Ser Cys Glu

12020 12025 12030

Thr Ile Ile Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu Ala Tyr

12035 12040 12045

Leu Pro Leu Asp Asp Asn Val Pro Ala Ala Arg Ile Glu Thr Ile

12050 12055 12060

Leu Ser Ala Val Pro Gly His Thr Leu Val Leu Leu Gly Ser His

12065 12070 12075

Val Ala Ala Pro Ser Ile Gly Leu Ala Asp Ala Glu Phe Val Asn

12080 12085 12090

Ile Asn His Thr Leu Gly His Ser Leu Gln Leu Asn Ser Thr Cys

12095 12100 12105

Ala Lys Leu Gln Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe

12110 12115 12120

Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Met Ile Glu His

12125 12130 12135

Arg Ser Ile Val Arg Leu Val Lys Asn Ser Asn Thr Leu Ala Lys

12140 12145 12150

Leu Pro Arg Ala Ala Arg Val Ala His Gln Phe Asn Leu Ala Phe

12155 12160 12165

Asp Ala Ala Asn Tyr Glu Ile Tyr Gly Thr Leu Leu Asn Gly Gly

12170 12175 12180

Ala Leu Ile Cys Val Asp Tyr Ser Thr Leu Leu Asp Ile Asp Ala

12185 12190 12195

Leu Val Ala Met Phe Lys Arg Glu Lys Ile Thr Ala Ser Ser Leu

12200 12205 12210

Ser Pro Gly Leu Leu Lys Gln Cys Val Asn Ser Ala Pro Glu Met

12215 12220 12225

Leu Lys Ala Leu Gln Val Ile Tyr Thr Gly Gly Asp Arg Leu Asp

12230 12235 12240

Gly Arg Asp Ala Ile Glu Leu Gln Ala Leu Val Pro Gly Gly Val

12245 12250 12255

Tyr Asn Met Tyr Gly Pro Thr Glu Asn Thr Val Ile Ser Thr Leu

12260 12265 12270

Tyr Asn Leu Gly Asp Lys His Ser Tyr Val Asn Gly Val Pro Ile

12275 12280 12285

Gly Thr Thr Val Ser Asn Ser Gly Ala Tyr Val Met Asp Ala Leu

12290 12295 12300

Gln Gln Leu Val Pro Val Gly Val Met Gly Glu Leu Val Val Thr

12305 12310 12315

Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro Glu Leu Asp Arg

12320 12325 12330

Asn Arg Phe Ile Lys Val Asn Ile Asp Gly Gln Val Val Arg Ala

12335 12340 12345

Tyr Arg Thr Gly Asp Arg Val Arg Tyr Arg Arg Ile Asp Gly Gln

12350 12355 12360

Leu Glu Phe Phe Gly Arg Met Asp Gln Gln Ile Lys Ile Arg Gly

12365 12370 12375

Phe Arg Ile Glu Thr Ala Glu Val Glu Asn Ala Met Leu Ser His

12380 12385 12390

Ser Ala Val Arg Asn Ala Ala Val Val Val Pro Thr Gln Asp Ile

12395 12400 12405

Gln Glu Lys Gly Met Ile Gly Phe Val Val Ile Glu Asn Asn Thr

12410 12415 12420

Pro Lys Asn Glu Glu Ser Lys Glu Glu His Leu Leu Gln Thr Glu

12425 12430 12435

Leu Ala Ile Leu Asn Arg Met Lys Ser Ile Leu Pro Pro Tyr Met

12440 12445 12450

Leu Pro Ser Arg Ile Ile Ile Leu Asp Gln Met Pro Ser Asn Phe

12455 12460 12465

Asn Gly Lys Val Asp Arg Lys Glu Leu Asp Arg Met Ala Gln Ser

12470 12475 12480

Val Pro Arg Gln Lys Thr Thr Ala Gly Arg Ile Val Pro Arg Asn

12485 12490 12495

Glu Leu Glu Ala Ser Leu Cys Lys Glu Phe Ala Glu Val Leu Gly

12500 12505 12510

Val Glu Val Gly Ile Thr Asp Asn Phe Phe Asp Leu Gly Gly His

12515 12520 12525

Ser Leu Leu Ala Thr Lys Leu Ala Ala Arg Ile Ser Arg Arg Leu

12530 12535 12540

Asp Thr Arg Val Ser Val Lys Asp Val Phe Asp Gln Pro Val Pro

12545 12550 12555

Ala Asp Leu Ala Leu Lys Val Ser Ser Tyr Ile Ser Gln Gly His

12560 12565 12570

Ala Met Asp Asn Gly Thr Leu Ser Thr Thr Asn Ser Ile Pro Phe

12575 12580 12585

Gln Leu Leu His Phe Glu Asp Ser Gln Lys Phe Ile Asp Arg Asp

12590 12595 12600

Ile Val Pro Gln Leu Ala His Gln Ser Ala Lys Ile Val Asp Val

12605 12610 12615

Tyr Pro Val Thr Trp Ile Gln Lys His Phe Leu Val Asp Pro Ala

12620 12625 12630

Thr Gly Leu Pro Arg Thr Pro Ser Leu Phe Phe Val Asp Phe Pro

12635 12640 12645

Ala Asn Ala Asp Cys Asp Lys Ile Cys Asn Ala Ser Arg Ser Leu

12650 12655 12660

Ile Gln Leu Phe Asp Ile Phe Arg Thr Val Phe Val Gln Ala Ala

12665 12670 12675

Gly Asn Phe Tyr Gln Val Val Leu Glu Glu Leu Asp Ile Pro Ile

12680 12685 12690

Ser Val Ile Glu Thr Glu Asp Ile Ser Thr Ala Thr Arg Val Leu

12695 12700 12705

Lys Glu Gln Asp Gln Gln Asn Pro Leu Gln Phe Gly Gln Gly Phe

12710 12715 12720

Leu Arg Phe Ala Val Val Lys Thr Arg Ser Ala Val Arg Leu Val

12725 12730 12735

Leu Arg Ile Ser His Cys Leu Tyr Asp Gly Leu Ser Phe Glu His

12740 12745 12750

Val Val Gln Ser Leu His Ala Leu Tyr Asn Gly Asp Arg Ile Pro

12755 12760 12765

Thr Gln Pro Lys Phe Val Gln Tyr Val Gln His Leu Thr Asp Ser

12770 12775 12780

Arg Lys Glu Gly Tyr Asp Phe Trp Leu Ser Val Leu Glu Glu Ser

12785 12790 12795

Ser Met Thr Val Val Glu Thr Gly Arg Arg Ala Gln Gln Leu Ser

12800 12805 12810

Ser Pro Glu Gly Ala Trp Phe Val Glu Lys Ile Ile Lys Ala Val

12815 12820 12825

Ile Pro Ala Asn Ser Asp Gly Ile Thr Gln Ala Thr Val Phe Thr

12830 12835 12840

Thr Ala Ser Thr Ile Leu Leu Ala Arg Met Thr Gly Ser Ser Asp

12845 12850 12855

Ile Thr Phe Ser Arg Leu Val Ser Gly Arg Gln Ser Leu Pro Ile

12860 12865 12870

Asn Asp Gln His Ile Val Gly Pro Cys Thr Asn Ile Val Pro Val

12875 12880 12885

Arg Ile Arg Met Thr Asp Gly Thr Asn Ala Arg Glu Leu Leu Gly

12890 12895 12900

Met Val Gln Asp Gln Tyr Ile Asp Ser Leu Pro Phe Glu Thr Leu

12905 12910 12915

Gly Phe Asp Asp Ile Lys Glu Asn Cys Thr Lys Trp Pro Ala Ser

12920 12925 12930

Thr Thr Asn Tyr Gly Cys Cys Ser Thr Phe Gln Asn Phe Glu Met

12935 12940 12945

Gln Pro Gln Ser Gln Val Gln Asp Glu Arg Val Arg Leu Ala Gly

12950 12955 12960

Leu Thr Asn Phe Lys Asp Ala Glu Leu Leu Asn Gly Ala Thr Ala

12965 12970 12975

Thr Asn Lys Arg Val Leu Asp Asp Val Pro Met His Glu Ile Asp

12980 12985 12990

Met Ile Gly Ile Pro Glu Pro Asp Gly Leu His Val Arg Val Val

12995 13000 13005

Leu Thr Ala Ser Arg Gln Ile Phe Glu Glu Glu Val Val Asp Arg

13010 13015 13020

Met His Glu Glu Phe Cys Asp Ile Ile Leu Gly Leu Asn Lys Ile

13025 13030 13035

Leu Gln Lys

13040

<210> 38

<211> 1197

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(1197)

<400> 38

atg acc ttt gtc gag act gta gcc gtc ccg gac aat gag gag cgt cct 48

Met Thr Phe Val Glu Thr Val Ala Val Pro Asp Asn Glu Glu Arg Pro

1 5 10 15

tcg gct gga cac aat cgt cct gta gcc gac agc acc aag tgt ccc aac 96

Ser Ala Gly His Asn Arg Pro Val Ala Asp Ser Thr Lys Cys Pro Asn

20 25 30

gcg agg gag atg aag gtt cag aat cgt gtc gcc caa agg aca cat cat 144

Ala Arg Glu Met Lys Val Gln Asn Arg Val Ala Gln Arg Thr His His

35 40 45

cgc cgt tta aaa aca aag ctg gaa gtg cta cgg gaa aga ttg aaa gag 192

Arg Arg Leu Lys Thr Lys Leu Glu Val Leu Arg Glu Arg Leu Lys Glu

50 55 60

cct gag aag caa gtt ggg gaa cct gcc agg gtc cag aca tcc acc tcc 240

Pro Glu Lys Gln Val Gly Glu Pro Ala Arg Val Gln Thr Ser Thr Ser

65 70 75 80

acg ctg gtg tcg gat gcg gca acc agc ttg gca gat tcg atg tgc ttg 288

Thr Leu Val Ser Asp Ala Ala Thr Ser Leu Ala Asp Ser Met Cys Leu

85 90 95

gtg cca gca gtg caa aat gac cag gcc atg gcg ttt gat ttc ctg atg 336

Val Pro Ala Val Gln Asn Asp Gln Ala Met Ala Phe Asp Phe Leu Met

100 105 110

acg cca tca cct tct gtt ggt aat gat tgt cct tca aat gac ctg gaa 384

Thr Pro Ser Pro Ser Val Gly Asn Asp Cys Pro Ser Asn Asp Leu Glu

115 120 125

acc atg cgc caa gct gcg tct gtt cat tcc aac acc tta ggc ggg gcc 432

Thr Met Arg Gln Ala Ala Ser Val His Ser Asn Thr Leu Gly Gly Ala

130 135 140

ttc ccg cta aac agg tcg ccc tgt act gag aac atg acg ccc gaa tcg 480

Phe Pro Leu Asn Arg Ser Pro Cys Thr Glu Asn Met Thr Pro Glu Ser

145 150 155 160

caa gtt agt tta tct acc gca cca tta tgt ttt act tct gtc gtc ccg 528

Gln Val Ser Leu Ser Thr Ala Pro Leu Cys Phe Thr Ser Val Val Pro

165 170 175

gcg gag ttg gac atg gac gct ttc tgc acg ctt gac agc agt gat tgg 576

Ala Glu Leu Asp Met Asp Ala Phe Cys Thr Leu Asp Ser Ser Asp Trp

180 185 190

tcg cgg ccg aat gaa gaa tct ctc cta cgt ttg gcc aat tat tct acc 624

Ser Arg Pro Asn Glu Glu Ser Leu Leu Arg Leu Ala Asn Tyr Ser Thr

195 200 205

tct gtg tca cct aca aac gtt caa tgg ggc gta gat gag aat gct ccg 672

Ser Val Ser Pro Thr Asn Val Gln Trp Gly Val Asp Glu Asn Ala Pro

210 215 220

ctc caa gat cgt gtg cgc tac atg agg gac caa gcc gtc gcc atg ggc 720

Leu Gln Asp Arg Val Arg Tyr Met Arg Asp Gln Ala Val Ala Met Gly

225 230 235 240

ttc ggc tct ctc gat gac gtc gtc gag gcg cac tac aca cag aag ctt 768

Phe Gly Ser Leu Asp Asp Val Val Glu Ala His Tyr Thr Gln Lys Leu

245 250 255

gag tgc acc agc cca tcg ttc caa gag cag cga ctg agt cgc aat cgg 816

Glu Cys Thr Ser Pro Ser Phe Gln Glu Gln Arg Leu Ser Arg Asn Arg

260 265 270

cga ctg tcg cga ctg ttg agc acg ctg cac aat gca gcc aaa gac tgg 864

Arg Leu Ser Arg Leu Leu Ser Thr Leu His Asn Ala Ala Lys Asp Trp

275 280 285

tcg gag tgg gag cga cgc ggg ttg caa gag caa gtt acc caa ggt gcc 912

Ser Glu Trp Glu Arg Arg Gly Leu Gln Glu Gln Val Thr Gln Gly Ala

290 295 300

gaa gac atc ttg gtc tcc gag cta aat tcg tac att aca cag cgc tcg 960

Glu Asp Ile Leu Val Ser Glu Leu Asn Ser Tyr Ile Thr Gln Arg Ser

305 310 315 320

atg aac tca acg gac gac aaa atc atc acg ggc ggc ctc ctg gac gag 1008

Met Asn Ser Thr Asp Asp Lys Ile Ile Thr Gly Gly Leu Leu Asp Glu

325 330 335

cag tct aga ctg agg cag gac gtg gaa gaa agg cgg aga ctc cag gac 1056

Gln Ser Arg Leu Arg Gln Asp Val Glu Glu Arg Arg Arg Leu Gln Asp

340 345 350

agt ctc ccc aac cta ggt gcc ctc ctc acc act ctg ctg tca agg tcc 1104

Ser Leu Pro Asn Leu Gly Ala Leu Leu Thr Thr Leu Leu Ser Arg Ser

355 360 365

aac gca ccc aac caa gac gcc cgt cga gac act gta ctc gcc atg atc 1152

Asn Ala Pro Asn Gln Asp Ala Arg Arg Asp Thr Val Leu Ala Met Ile

370 375 380

aag aca atg tgc ttt gat caa gac gag aac atg agt ata tca tag 1197

Lys Thr Met Cys Phe Asp Gln Asp Glu Asn Met Ser Ile Ser

385 390 395

<210> 39

<211> 398

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 39

Met Thr Phe Val Glu Thr Val Ala Val Pro Asp Asn Glu Glu Arg Pro

1 5 10 15

Ser Ala Gly His Asn Arg Pro Val Ala Asp Ser Thr Lys Cys Pro Asn

20 25 30

Ala Arg Glu Met Lys Val Gln Asn Arg Val Ala Gln Arg Thr His His

35 40 45

Arg Arg Leu Lys Thr Lys Leu Glu Val Leu Arg Glu Arg Leu Lys Glu

50 55 60

Pro Glu Lys Gln Val Gly Glu Pro Ala Arg Val Gln Thr Ser Thr Ser

65 70 75 80

Thr Leu Val Ser Asp Ala Ala Thr Ser Leu Ala Asp Ser Met Cys Leu

85 90 95

Val Pro Ala Val Gln Asn Asp Gln Ala Met Ala Phe Asp Phe Leu Met

100 105 110

Thr Pro Ser Pro Ser Val Gly Asn Asp Cys Pro Ser Asn Asp Leu Glu

115 120 125

Thr Met Arg Gln Ala Ala Ser Val His Ser Asn Thr Leu Gly Gly Ala

130 135 140

Phe Pro Leu Asn Arg Ser Pro Cys Thr Glu Asn Met Thr Pro Glu Ser

145 150 155 160

Gln Val Ser Leu Ser Thr Ala Pro Leu Cys Phe Thr Ser Val Val Pro

165 170 175

Ala Glu Leu Asp Met Asp Ala Phe Cys Thr Leu Asp Ser Ser Asp Trp

180 185 190

Ser Arg Pro Asn Glu Glu Ser Leu Leu Arg Leu Ala Asn Tyr Ser Thr

195 200 205

Ser Val Ser Pro Thr Asn Val Gln Trp Gly Val Asp Glu Asn Ala Pro

210 215 220

Leu Gln Asp Arg Val Arg Tyr Met Arg Asp Gln Ala Val Ala Met Gly

225 230 235 240

Phe Gly Ser Leu Asp Asp Val Val Glu Ala His Tyr Thr Gln Lys Leu

245 250 255

Glu Cys Thr Ser Pro Ser Phe Gln Glu Gln Arg Leu Ser Arg Asn Arg

260 265 270

Arg Leu Ser Arg Leu Leu Ser Thr Leu His Asn Ala Ala Lys Asp Trp

275 280 285

Ser Glu Trp Glu Arg Arg Gly Leu Gln Glu Gln Val Thr Gln Gly Ala

290 295 300

Glu Asp Ile Leu Val Ser Glu Leu Asn Ser Tyr Ile Thr Gln Arg Ser

305 310 315 320

Met Asn Ser Thr Asp Asp Lys Ile Ile Thr Gly Gly Leu Leu Asp Glu

325 330 335

Gln Ser Arg Leu Arg Gln Asp Val Glu Glu Arg Arg Arg Leu Gln Asp

340 345 350

Ser Leu Pro Asn Leu Gly Ala Leu Leu Thr Thr Leu Leu Ser Arg Ser

355 360 365

Asn Ala Pro Asn Gln Asp Ala Arg Arg Asp Thr Val Leu Ala Met Ile

370 375 380

Lys Thr Met Cys Phe Asp Gln Asp Glu Asn Met Ser Ile Ser

385 390 395

<210> 40

<211> 1269

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(1269)

<400> 40

atg gac ccg aga cag tca cgg atc acg gag ctg gca ata gcc atc aaa 48

Met Asp Pro Arg Gln Ser Arg Ile Thr Glu Leu Ala Ile Ala Ile Lys

1 5 10 15

aag cag acg gaa aca ctg cag tca cta ttg gac agt ctc aaa gtt gcg 96

Lys Gln Thr Glu Thr Leu Gln Ser Leu Leu Asp Ser Leu Lys Val Ala

20 25 30

acg cct tct ttt tct gta aac gcc aat cag gag ttg cct cgc aat gca 144

Thr Pro Ser Phe Ser Val Asn Ala Asn Gln Glu Leu Pro Arg Asn Ala

35 40 45

gct gtt cag ctc gcg cag tcc tct atc ctc gac tcc tgt acg gaa ctg 192

Ala Val Gln Leu Ala Gln Ser Ser Ile Leu Asp Ser Cys Thr Glu Leu

50 55 60

cag gat ttg gtc gaa ggc cct ctg gca cat gtt ggg cga ata atg agc 240

Gln Asp Leu Val Glu Gly Pro Leu Ala His Val Gly Arg Ile Met Ser

65 70 75 80

cct cga gtt cat ata tcg tca gct ctg caa gct att gta cat ttc aat 288

Pro Arg Val His Ile Ser Ser Ala Leu Gln Ala Ile Val His Phe Asn

85 90 95

ata gca gag aaa atc gca aaa cac gag act atc tca ttt ggc gag atc 336

Ile Ala Glu Lys Ile Ala Lys His Glu Thr Ile Ser Phe Gly Glu Ile

100 105 110

gca aaa aga tgc aaa atg gac gta gat gat gtc aag cga att atg cga 384

Ala Lys Arg Cys Lys Met Asp Val Asp Asp Val Lys Arg Ile Met Arg

115 120 125

tta gcc atc tcg tac cga atc ttc aaa gag tct cat atc gga ttt gta 432

Leu Ala Ile Ser Tyr Arg Ile Phe Lys Glu Ser His Ile Gly Phe Val

130 135 140

aat cac acg gct agc tca ttc ttg att gcg gaa aac ctt ctt gtg agg 480

Asn His Thr Ala Ser Ser Phe Leu Ile Ala Glu Asn Leu Leu Val Arg

145 150 155 160

caa tgg att agt ctt tgc tgt gat gag ttc ata cca gcg ggt tcg ttc 528

Gln Trp Ile Ser Leu Cys Cys Asp Glu Phe Ile Pro Ala Gly Ser Phe

165 170 175

ctt gtt cct gcc atg aaa aaa tgg cct agc tct gaa gag cct aac gag 576

Leu Val Pro Ala Met Lys Lys Trp Pro Ser Ser Glu Glu Pro Asn Glu

180 185 190

acc gcg ttt gcg ctg ctt cat aag gga gat agt cta tgg gaa gtc ctt 624

Thr Ala Phe Ala Leu Leu His Lys Gly Asp Ser Leu Trp Glu Val Leu

195 200 205

aaa aag cag cct gaa aaa gct cag cgc ttt gct cac gga atg gag tac 672

Lys Lys Gln Pro Glu Lys Ala Gln Arg Phe Ala His Gly Met Glu Tyr

210 215 220

atg cgg aca ctc ccg cca ttc gac atc aac cat ctg ttt acc tcg ttg 720

Met Arg Thr Leu Pro Pro Phe Asp Ile Asn His Leu Phe Thr Ser Leu

225 230 235 240

aac tgg gag atc gac tgt gag atg gtt ttg gtg gac gtg ggc ggt tct 768

Asn Trp Glu Ile Asp Cys Glu Met Val Leu Val Asp Val Gly Gly Ser

245 250 255

caa ggc tcc att gct gaa gct tta ctt cga aga cac ccg cga cta cga 816

Gln Gly Ser Ile Ala Glu Ala Leu Leu Arg Arg His Pro Arg Leu Arg

260 265 270

tgt tac gtt caa gac ctt cca gag acc ttg agc aaa gcc gtc gtg ccc 864

Cys Tyr Val Gln Asp Leu Pro Glu Thr Leu Ser Lys Ala Val Val Pro

275 280 285

aag gat ctc aag ggt cgt ctt gag ttc gta agc cac agc atg ttc aaa 912

Lys Asp Leu Lys Gly Arg Leu Glu Phe Val Ser His Ser Met Phe Lys

290 295 300

gag cag cct ata aaa gcc gac gta tac ttg ctc agg tca att ttg cac 960

Glu Gln Pro Ile Lys Ala Asp Val Tyr Leu Leu Arg Ser Ile Leu His

305 310 315 320

gac tgg tta gat gga tac gcc ctg caa atc atc cgg aac ctg att ccc 1008

Asp Trp Leu Asp Gly Tyr Ala Leu Gln Ile Ile Arg Asn Leu Ile Pro

325 330 335

gct ctc gag gtt gga tcc aag gtg att ata aat gag atc tgt cta ccg 1056

Ala Leu Glu Val Gly Ser Lys Val Ile Ile Asn Glu Ile Cys Leu Pro

340 345 350

gag cca aac gcc atc tca gca tat gag gca cag ctt att cgc ggg tac 1104

Glu Pro Asn Ala Ile Ser Ala Tyr Glu Ala Gln Leu Ile Arg Gly Tyr

355 360 365

gat ctt tca atg aag caa caa ttt aat tcg aaa gag cga gat gtg cac 1152

Asp Leu Ser Met Lys Gln Gln Phe Asn Ser Lys Glu Arg Asp Val His

370 375 380

gag tgg gaa act ctg ttc cga ctt gca gac aga cgg ttc aaa cta aat 1200

Glu Trp Glu Thr Leu Phe Arg Leu Ala Asp Arg Arg Phe Lys Leu Asn

385 390 395 400

cgc atc gtc aat cca cca ggc tca ttc ctt gcc gtt cta gaa ttc gaa 1248

Arg Ile Val Asn Pro Pro Gly Ser Phe Leu Ala Val Leu Glu Phe Glu

405 410 415

tgg caa ccc acc aca cca taa 1269

Trp Gln Pro Thr Thr Pro

420

<210> 41

<211> 422

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 41

Met Asp Pro Arg Gln Ser Arg Ile Thr Glu Leu Ala Ile Ala Ile Lys

1 5 10 15

Lys Gln Thr Glu Thr Leu Gln Ser Leu Leu Asp Ser Leu Lys Val Ala

20 25 30

Thr Pro Ser Phe Ser Val Asn Ala Asn Gln Glu Leu Pro Arg Asn Ala

35 40 45

Ala Val Gln Leu Ala Gln Ser Ser Ile Leu Asp Ser Cys Thr Glu Leu

50 55 60

Gln Asp Leu Val Glu Gly Pro Leu Ala His Val Gly Arg Ile Met Ser

65 70 75 80

Pro Arg Val His Ile Ser Ser Ala Leu Gln Ala Ile Val His Phe Asn

85 90 95

Ile Ala Glu Lys Ile Ala Lys His Glu Thr Ile Ser Phe Gly Glu Ile

100 105 110

Ala Lys Arg Cys Lys Met Asp Val Asp Asp Val Lys Arg Ile Met Arg

115 120 125

Leu Ala Ile Ser Tyr Arg Ile Phe Lys Glu Ser His Ile Gly Phe Val

130 135 140

Asn His Thr Ala Ser Ser Phe Leu Ile Ala Glu Asn Leu Leu Val Arg

145 150 155 160

Gln Trp Ile Ser Leu Cys Cys Asp Glu Phe Ile Pro Ala Gly Ser Phe

165 170 175

Leu Val Pro Ala Met Lys Lys Trp Pro Ser Ser Glu Glu Pro Asn Glu

180 185 190

Thr Ala Phe Ala Leu Leu His Lys Gly Asp Ser Leu Trp Glu Val Leu

195 200 205

Lys Lys Gln Pro Glu Lys Ala Gln Arg Phe Ala His Gly Met Glu Tyr

210 215 220

Met Arg Thr Leu Pro Pro Phe Asp Ile Asn His Leu Phe Thr Ser Leu

225 230 235 240

Asn Trp Glu Ile Asp Cys Glu Met Val Leu Val Asp Val Gly Gly Ser

245 250 255

Gln Gly Ser Ile Ala Glu Ala Leu Leu Arg Arg His Pro Arg Leu Arg

260 265 270

Cys Tyr Val Gln Asp Leu Pro Glu Thr Leu Ser Lys Ala Val Val Pro

275 280 285

Lys Asp Leu Lys Gly Arg Leu Glu Phe Val Ser His Ser Met Phe Lys

290 295 300

Glu Gln Pro Ile Lys Ala Asp Val Tyr Leu Leu Arg Ser Ile Leu His

305 310 315 320

Asp Trp Leu Asp Gly Tyr Ala Leu Gln Ile Ile Arg Asn Leu Ile Pro

325 330 335

Ala Leu Glu Val Gly Ser Lys Val Ile Ile Asn Glu Ile Cys Leu Pro

340 345 350

Glu Pro Asn Ala Ile Ser Ala Tyr Glu Ala Gln Leu Ile Arg Gly Tyr

355 360 365

Asp Leu Ser Met Lys Gln Gln Phe Asn Ser Lys Glu Arg Asp Val His

370 375 380

Glu Trp Glu Thr Leu Phe Arg Leu Ala Asp Arg Arg Phe Lys Leu Asn

385 390 395 400

Arg Ile Val Asn Pro Pro Gly Ser Phe Leu Ala Val Leu Glu Phe Glu

405 410 415

Trp Gln Pro Thr Thr Pro

420

<210> 42

<211> 1617

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(1617)

<400> 42

atg act gaa ccc aca tgg aag aca gtt gca tcg gag aaa cag cag cag 48

Met Thr Glu Pro Thr Trp Lys Thr Val Ala Ser Glu Lys Gln Gln Gln

1 5 10 15

cgt gaa tcc aaa atc cct tca gaa tgg caa att ccg aag tcg tcg cat 96

Arg Glu Ser Lys Ile Pro Ser Glu Trp Gln Ile Pro Lys Ser Ser His

20 25 30

cca gct ccc gaa gta acc ttt gtt caa gac ttc cca gcc aaa tcg gga 144

Pro Ala Pro Glu Val Thr Phe Val Gln Asp Phe Pro Ala Lys Ser Gly

35 40 45

atg ttc acc aat cga gag ctg caa cta aca gcg gcg act gca tcg gat 192

Met Phe Thr Asn Arg Glu Leu Gln Leu Thr Ala Ala Thr Ala Ser Asp

50 55 60

gta acg gcc aag atc tcc act ggc gaa tgg acg gcc gtg gag gtc acg 240

Val Thr Ala Lys Ile Ser Thr Gly Glu Trp Thr Ala Val Glu Val Thr

65 70 75 80

act gct gtg tgc aag cga gct gcc gtg gct caa caa ttg ttg aat tgt 288

Thr Ala Val Cys Lys Arg Ala Ala Val Ala Gln Gln Leu Leu Asn Cys

85 90 95

gta acg gag atc tgc ttt gat caa gct ata gca aga gcg aag gag ctt 336

Val Thr Glu Ile Cys Phe Asp Gln Ala Ile Ala Arg Ala Lys Glu Leu

100 105 110

gac gcg tat ttt gaa aaa gaa gga aag acc gtg ggc cca ctc cac gga 384

Asp Ala Tyr Phe Glu Lys Glu Gly Lys Thr Val Gly Pro Leu His Gly

115 120 125

tta cca att agc ttc aaa gac cag ttc aat gtc aaa ggc ttc gac tcc 432

Leu Pro Ile Ser Phe Lys Asp Gln Phe Asn Val Lys Gly Phe Asp Ser

130 135 140

acc atc ggc tac tgc agt tat gct agc aag cca gca acg gca gac tca 480

Thr Ile Gly Tyr Cys Ser Tyr Ala Ser Lys Pro Ala Thr Ala Asp Ser

145 150 155 160

act ctc gtc aag ctc ctg gtc aag gct ggg gca atc atc tat gtc aag 528

Thr Leu Val Lys Leu Leu Val Lys Ala Gly Ala Ile Ile Tyr Val Lys

165 170 175

tcc aat gtt cct atc acg cta atg atg ggc gag tca ttc aac aac atc 576

Ser Asn Val Pro Ile Thr Leu Met Met Gly Glu Ser Phe Asn Asn Ile

180 185 190

ttt gga cgc aca ctc aac ccc cgc aat cgg gag ttg acc aca gga ggc 624

Phe Gly Arg Thr Leu Asn Pro Arg Asn Arg Glu Leu Thr Thr Gly Gly

195 200 205

tca tca ggc gga gaa gca gca ctg gtc acg ttc tgt gcc agc ttc ctc 672

Ser Ser Gly Gly Glu Ala Ala Leu Val Thr Phe Cys Ala Ser Phe Leu

210 215 220

ggt gtg ggc acc gac atc ggt ggc agc ctt cgc ata cca tgc tca ttc 720

Gly Val Gly Thr Asp Ile Gly Gly Ser Leu Arg Ile Pro Cys Ser Phe

225 230 235 240

acc ggg ctg tat ggg cta aga cca tcc cac ggc aga gtg tca tat caa 768

Thr Gly Leu Tyr Gly Leu Arg Pro Ser His Gly Arg Val Ser Tyr Gln

245 250 255

cat gtg cag aac acc ttg ctc gga cag gaa gca gtc aga tca tgt gct 816

His Val Gln Asn Thr Leu Leu Gly Gln Glu Ala Val Arg Ser Cys Ala

260 265 270

gga ccc atg tgc cgt gca ccg gaa gat atc cgc ttg ttc atg tcg agt 864

Gly Pro Met Cys Arg Ala Pro Glu Asp Ile Arg Leu Phe Met Ser Ser

275 280 285

cta gct gcc cag cag ccc tgg ctt tgg gat ccc cag agt ctg cca ctc 912

Leu Ala Ala Gln Gln Pro Trp Leu Trp Asp Pro Gln Ser Leu Pro Leu

290 295 300

cca tgg cgg gcg gag gaa gag gtc tta ccg aag aag ttg tgt ttc ggt 960

Pro Trp Arg Ala Glu Glu Glu Val Leu Pro Lys Lys Leu Cys Phe Gly

305 310 315 320

ttt gct cta ggt gat ggc cat gta ggc ccg aaa aag tta aag caa gca 1008

Phe Ala Leu Gly Asp Gly His Val Gly Pro Lys Lys Leu Lys Gln Ala

325 330 335

ggg cat gct gtc att aac ttc aat ctc aca gaa gga aaa gaa gta aat 1056

Gly His Ala Val Ile Asn Phe Asn Leu Thr Glu Gly Lys Glu Val Asn

340 345 350

gag atc atg aac aag atg ttc act gcg gat ggg ggt gcc gag ttt cag 1104

Glu Ile Met Asn Lys Met Phe Thr Ala Asp Gly Gly Ala Glu Phe Gln

355 360 365

cgc gac acc gat gcc acg ggc gag ccc ctg cca cct aca gta gaa tac 1152

Arg Asp Thr Asp Ala Thr Gly Glu Pro Leu Pro Pro Thr Val Glu Tyr

370 375 380

tgg ctc ggc cac agc tcg caa atc aaa gcc tca acc gta agc gag aca 1200

Trp Leu Gly His Ser Ser Gln Ile Lys Ala Ser Thr Val Ser Glu Thr

385 390 395 400

tgg aaa aat cag cac aag aag gcg ttg ctt gcg caa aag ttc cta gag 1248

Trp Lys Asn Gln His Lys Lys Ala Leu Leu Ala Gln Lys Phe Leu Glu

405 410 415

aag tgg caa gca acc aaa ggg cga acg ggc acg agt cgc cct atc gat 1296

Lys Trp Gln Ala Thr Lys Gly Arg Thr Gly Thr Ser Arg Pro Ile Asp

420 425 430

ggg ctg atc atg cca tcg acg cca ttt ccg gcc agt cgt cac ggc agc 1344

Gly Leu Ile Met Pro Ser Thr Pro Phe Pro Ala Ser Arg His Gly Ser

435 440 445

ggc tgg cca tgg cac ttt ggt gat ctc tct gcc cta cta gat ctg acc 1392

Gly Trp Pro Trp His Phe Gly Asp Leu Ser Ala Leu Leu Asp Leu Thr

450 455 460

acg ggc gtt ttc cca gtc acc cgg gtc aat ctg gag aaa gac gcc gtg 1440

Thr Gly Val Phe Pro Val Thr Arg Val Asn Leu Glu Lys Asp Ala Val

465 470 475 480

ccg ccg agc tgg acg ccc atg tct gtg aaa gac aag gag gcg atg gat 1488

Pro Pro Ser Trp Thr Pro Met Ser Val Lys Asp Lys Glu Ala Met Asp

485 490 495

tac tat gag aag cca gag aat cac gag aat gcc cta gtc ggc ctc caa 1536

Tyr Tyr Glu Lys Pro Glu Asn His Glu Asn Ala Leu Val Gly Leu Gln

500 505 510

ttg att ggt aga agg ttg gag gag gaa aag gta aca gct atg ctt acg 1584

Leu Ile Gly Arg Arg Leu Glu Glu Glu Lys Val Thr Ala Met Leu Thr

515 520 525

ctt att agg aat gtg ctt gaa gta gat tat taa 1617

Leu Ile Arg Asn Val Leu Glu Val Asp Tyr

530 535

<210> 43

<211> 538

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 43

Met Thr Glu Pro Thr Trp Lys Thr Val Ala Ser Glu Lys Gln Gln Gln

1 5 10 15

Arg Glu Ser Lys Ile Pro Ser Glu Trp Gln Ile Pro Lys Ser Ser His

20 25 30

Pro Ala Pro Glu Val Thr Phe Val Gln Asp Phe Pro Ala Lys Ser Gly

35 40 45

Met Phe Thr Asn Arg Glu Leu Gln Leu Thr Ala Ala Thr Ala Ser Asp

50 55 60

Val Thr Ala Lys Ile Ser Thr Gly Glu Trp Thr Ala Val Glu Val Thr

65 70 75 80

Thr Ala Val Cys Lys Arg Ala Ala Val Ala Gln Gln Leu Leu Asn Cys

85 90 95

Val Thr Glu Ile Cys Phe Asp Gln Ala Ile Ala Arg Ala Lys Glu Leu

100 105 110

Asp Ala Tyr Phe Glu Lys Glu Gly Lys Thr Val Gly Pro Leu His Gly

115 120 125

Leu Pro Ile Ser Phe Lys Asp Gln Phe Asn Val Lys Gly Phe Asp Ser

130 135 140

Thr Ile Gly Tyr Cys Ser Tyr Ala Ser Lys Pro Ala Thr Ala Asp Ser

145 150 155 160

Thr Leu Val Lys Leu Leu Val Lys Ala Gly Ala Ile Ile Tyr Val Lys

165 170 175

Ser Asn Val Pro Ile Thr Leu Met Met Gly Glu Ser Phe Asn Asn Ile

180 185 190

Phe Gly Arg Thr Leu Asn Pro Arg Asn Arg Glu Leu Thr Thr Gly Gly

195 200 205

Ser Ser Gly Gly Glu Ala Ala Leu Val Thr Phe Cys Ala Ser Phe Leu

210 215 220

Gly Val Gly Thr Asp Ile Gly Gly Ser Leu Arg Ile Pro Cys Ser Phe

225 230 235 240

Thr Gly Leu Tyr Gly Leu Arg Pro Ser His Gly Arg Val Ser Tyr Gln

245 250 255

His Val Gln Asn Thr Leu Leu Gly Gln Glu Ala Val Arg Ser Cys Ala

260 265 270

Gly Pro Met Cys Arg Ala Pro Glu Asp Ile Arg Leu Phe Met Ser Ser

275 280 285

Leu Ala Ala Gln Gln Pro Trp Leu Trp Asp Pro Gln Ser Leu Pro Leu

290 295 300

Pro Trp Arg Ala Glu Glu Glu Val Leu Pro Lys Lys Leu Cys Phe Gly

305 310 315 320

Phe Ala Leu Gly Asp Gly His Val Gly Pro Lys Lys Leu Lys Gln Ala

325 330 335

Gly His Ala Val Ile Asn Phe Asn Leu Thr Glu Gly Lys Glu Val Asn

340 345 350

Glu Ile Met Asn Lys Met Phe Thr Ala Asp Gly Gly Ala Glu Phe Gln

355 360 365

Arg Asp Thr Asp Ala Thr Gly Glu Pro Leu Pro Pro Thr Val Glu Tyr

370 375 380

Trp Leu Gly His Ser Ser Gln Ile Lys Ala Ser Thr Val Ser Glu Thr

385 390 395 400

Trp Lys Asn Gln His Lys Lys Ala Leu Leu Ala Gln Lys Phe Leu Glu

405 410 415

Lys Trp Gln Ala Thr Lys Gly Arg Thr Gly Thr Ser Arg Pro Ile Asp

420 425 430

Gly Leu Ile Met Pro Ser Thr Pro Phe Pro Ala Ser Arg His Gly Ser

435 440 445

Gly Trp Pro Trp His Phe Gly Asp Leu Ser Ala Leu Leu Asp Leu Thr

450 455 460

Thr Gly Val Phe Pro Val Thr Arg Val Asn Leu Glu Lys Asp Ala Val

465 470 475 480

Pro Pro Ser Trp Thr Pro Met Ser Val Lys Asp Lys Glu Ala Met Asp

485 490 495

Tyr Tyr Glu Lys Pro Glu Asn His Glu Asn Ala Leu Val Gly Leu Gln

500 505 510

Leu Ile Gly Arg Arg Leu Glu Glu Glu Lys Val Thr Ala Met Leu Thr

515 520 525

Leu Ile Arg Asn Val Leu Glu Val Asp Tyr

530 535

<210> 44

<211> 2991

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(2991)

<400> 44

atg gcg ttg caa gag cgc cgt gcc gcg gtc aca agt tcc gat atc ctc 48

Met Ala Leu Gln Glu Arg Arg Ala Ala Val Thr Ser Ser Asp Ile Leu

1 5 10 15

tca gcg cat gct atc tcg tct ccc gcc ttg gcc gca gcg gcc atc aat 96

Ser Ala His Ala Ile Ser Ser Pro Ala Leu Ala Ala Ala Ala Ile Asn

20 25 30

ttc gcc gcc agc ttc cat cga gat gcc cgc acc tgt tgc agc gct cat 144

Phe Ala Ala Ser Phe His Arg Asp Ala Arg Thr Cys Cys Ser Ala His

35 40 45

gag cgt agc cag ctc cag aaa gtc tac cgc gac aag atc ctc gcc aac 192

Glu Arg Ser Gln Leu Gln Lys Val Tyr Arg Asp Lys Ile Leu Ala Asn

50 55 60

gac aag ttt acg gcc aac att gct gct gcc ttc ctc tct gtc ctg ggc 240

Asp Lys Phe Thr Ala Asn Ile Ala Ala Ala Phe Leu Ser Val Leu Gly

65 70 75 80

ccc aac gcc ggc cgt aac gat gca ggt gcc gag cgc gag cgc tgg ggc 288

Pro Asn Ala Gly Arg Asn Asp Ala Gly Ala Glu Arg Glu Arg Trp Gly

85 90 95

gac ttt gac cgc ctg gcg cag cga ggc aag aac atg cgc gac cgc gag 336

Asp Phe Asp Arg Leu Ala Gln Arg Gly Lys Asn Met Arg Asp Arg Glu

100 105 110

agc cag cat ttg caa cat cag tca ggc atc att gcc gcc tgg ggg cct 384

Ser Gln His Leu Gln His Gln Ser Gly Ile Ile Ala Ala Trp Gly Pro

115 120 125

cga tgc ttc gag tac tac ggc tgg cat gtc ctg ccg ctg ccg ctg ctg 432

Arg Cys Phe Glu Tyr Tyr Gly Trp His Val Leu Pro Leu Pro Leu Leu

130 135 140

cgt cag gtg cac gac ctt gcc gtg ctg ata cct agc tgg gac gac gcc 480

Arg Gln Val His Asp Leu Ala Val Leu Ile Pro Ser Trp Asp Asp Ala

145 150 155 160

gtt gag ctg ctg aat tcc agg atg ctg ttg cgc cac gaa ctg cgt gtg 528

Val Glu Leu Leu Asn Ser Arg Met Leu Leu Arg His Glu Leu Arg Val

165 170 175

ctg cac ggc aac aac aag gcc ctc cga atc ggt gaa cac tct gcc gct 576

Leu His Gly Asn Asn Lys Ala Leu Arg Ile Gly Glu His Ser Ala Ala

180 185 190

tcc aaa gtt cag gac tca cgc tca cct gtt gag cgt acc gac atc gtg 624

Ser Lys Val Gln Asp Ser Arg Ser Pro Val Glu Arg Thr Asp Ile Val

195 200 205

gct gct ctc gac tgg gct cgt gcc aac gca act tcg gct gcg gca cgt 672

Ala Ala Leu Asp Trp Ala Arg Ala Asn Ala Thr Ser Ala Ala Ala Arg

210 215 220

caa gcg gtc aag gaa gcg gcg cag ggc atg aat ggg act ccg atc aac 720

Gln Ala Val Lys Glu Ala Ala Gln Gly Met Asn Gly Thr Pro Ile Asn

225 230 235 240

aca ttc ggt ttg aag cga gat tgc tat ggt atg gtc gta ccg tcg gtc 768

Thr Phe Gly Leu Lys Arg Asp Cys Tyr Gly Met Val Val Pro Ser Val

245 250 255

ggc ccc tac gat cct gat gga gat gat gac aat gat gaa gac gtt gtc 816

Gly Pro Tyr Asp Pro Asp Gly Asp Asp Asp Asn Asp Glu Asp Val Val

260 265 270

gat gtg tcc cct cgg cca gcg aag cac atc aaa ttg tca gcc gca gag 864

Asp Val Ser Pro Arg Pro Ala Lys His Ile Lys Leu Ser Ala Ala Glu

275 280 285

ccg ctt cgt ctg atg ttt cca ggt tca ttg agt cat gtc cag gct tgt 912

Pro Leu Arg Leu Met Phe Pro Gly Ser Leu Ser His Val Gln Ala Cys

290 295 300

caa aga cat gac act gac ggc gag aag gcc agt act gca ccc att cgt 960

Gln Arg His Asp Thr Asp Gly Glu Lys Ala Ser Thr Ala Pro Ile Arg

305 310 315 320

agt aac aaa ctg tcc cag tcc aaa cag cca gag cta gac aca gca gcc 1008

Ser Asn Lys Leu Ser Gln Ser Lys Gln Pro Glu Leu Asp Thr Ala Ala

325 330 335

gag agt ctt cgt acg agg cat att cac aat gaa cgc atc aac gag ccc 1056

Glu Ser Leu Arg Thr Arg His Ile His Asn Glu Arg Ile Asn Glu Pro

340 345 350

ctc gac gaa gtc tcg gac tgc agt cta tct ctc caa aca ata gcc gtg 1104

Leu Asp Glu Val Ser Asp Cys Ser Leu Ser Leu Gln Thr Ile Ala Val

355 360 365

gga gga ggg agc gct cag gag gaa acg cca gac caa gat gtg gaa cat 1152

Gly Gly Gly Ser Ala Gln Glu Glu Thr Pro Asp Gln Asp Val Glu His

370 375 380

gca cat cct gaa gtt gag ata aca tcc gcc ata agc agt gag ctt agg 1200

Ala His Pro Glu Val Glu Ile Thr Ser Ala Ile Ser Ser Glu Leu Arg

385 390 395 400

aag gta gac gag cgt acc gat ggt ata agg ata ggg cgt gtg att atg 1248

Lys Val Asp Glu Arg Thr Asp Gly Ile Arg Ile Gly Arg Val Ile Met

405 410 415

agg cgc agt cac tgt atg gta aga gaa cag gac aac cag act aac gag 1296

Arg Arg Ser His Cys Met Val Arg Glu Gln Asp Asn Gln Thr Asn Glu

420 425 430

gag ggg aca gga gaa gta cag tca cag cgg gac agg aga gcg agg gac 1344

Glu Gly Thr Gly Glu Val Gln Ser Gln Arg Asp Arg Arg Ala Arg Asp

435 440 445

ttg gga aag gat atg gag acg gat atg gat att gac agc cag ctg gag 1392

Leu Gly Lys Asp Met Glu Thr Asp Met Asp Ile Asp Ser Gln Leu Glu

450 455 460

gag atg ctg gac ata cat gct ctg gag gcg caa aga aat cac gaa gaa 1440

Glu Met Leu Asp Ile His Ala Leu Glu Ala Gln Arg Asn His Glu Glu

465 470 475 480

atg tcg gat ggt gaa gat gtt gtt gca gga gtg gcg ggc ccg gga acg 1488

Met Ser Asp Gly Glu Asp Val Val Ala Gly Val Ala Gly Pro Gly Thr

485 490 495

cca acg cac agg gcg gcg gaa gaa gga gga tgc aga gaa aaa gaa gca 1536

Pro Thr His Arg Ala Ala Glu Glu Gly Gly Cys Arg Glu Lys Glu Ala

500 505 510

gag aat gcc aaa acg gat gag gag caa gtg cag gac aaa gca gct ctg 1584

Glu Asn Ala Lys Thr Asp Glu Glu Gln Val Gln Asp Lys Ala Ala Leu

515 520 525

gat cag gcg gga aat act aat acg aat cga gag gta gaa aac gca gca 1632

Asp Gln Ala Gly Asn Thr Asn Thr Asn Arg Glu Val Glu Asn Ala Ala

530 535 540

cca aaa gcg cac agc caa gaa ggt gcc ctg cgt gca tcg cga acg ggc 1680

Pro Lys Ala His Ser Gln Glu Gly Ala Leu Arg Ala Ser Arg Thr Gly

545 550 555 560

acg atc gtg gaa agg aca gtg gag tta cac tca acg cac tca att cat 1728

Thr Ile Val Glu Arg Thr Val Glu Leu His Ser Thr His Ser Ile His

565 570 575

caa aga gcg agt gtg aat acg acg gct cca acc gtg gcg cga tca agc 1776

Gln Arg Ala Ser Val Asn Thr Thr Ala Pro Thr Val Ala Arg Ser Ser

580 585 590

gat agc gac gac agc gat tca ctc cat tca ccc acg gcg ctt caa aat 1824

Asp Ser Asp Asp Ser Asp Ser Leu His Ser Pro Thr Ala Leu Gln Asn

595 600 605

ctg caa gcc tat atc gat acc aga act cac caa ctc act caa gtg ctg 1872

Leu Gln Ala Tyr Ile Asp Thr Arg Thr His Gln Leu Thr Gln Val Leu

610 615 620

agc cag ctc aac tca aca cct gac gtc aga cac cac gct caa ctg cag 1920

Ser Gln Leu Asn Ser Thr Pro Asp Val Arg His His Ala Gln Leu Gln

625 630 635 640

ctt gac tgg tta agt ccg caa cga tgg gcc agt gtc tac gtg gag cca 1968

Leu Asp Trp Leu Ser Pro Gln Arg Trp Ala Ser Val Tyr Val Glu Pro

645 650 655

gaa cat cac atg ggc gcc act tcc tca gca tca tca gac agc gct gac 2016

Glu His His Met Gly Ala Thr Ser Ser Ala Ser Ser Asp Ser Ala Asp

660 665 670

att tgg tgt ctg gac tgg gat acg ttc cac cag tat gct gac agc aac 2064

Ile Trp Cys Leu Asp Trp Asp Thr Phe His Gln Tyr Ala Asp Ser Asn

675 680 685

cat gtc ttc cgg cgg cct gtt gtt atc aag caa aag ttc cag gac agc 2112

His Val Phe Arg Arg Pro Val Val Ile Lys Gln Lys Phe Gln Asp Ser

690 695 700

ggt atg tat gag gtt gac aga tac gtg gat atg ctg tgg cag cgc ttt 2160

Gly Met Tyr Glu Val Asp Arg Tyr Val Asp Met Leu Trp Gln Arg Phe

705 710 715 720

ccg gag cag cat att gag gtc caa aac agc att aca ggc act agt cga 2208

Pro Glu Gln His Ile Glu Val Gln Asn Ser Ile Thr Gly Thr Ser Arg

725 730 735

ttg atg agc atg gcc gag tat tgc tct acg gct ttg act gtt acg gag 2256

Leu Met Ser Met Ala Glu Tyr Cys Ser Thr Ala Leu Thr Val Thr Glu

740 745 750

gct ggc acg agt ctg tct gac aat act acc tcc gtg agc aac gct gtt 2304

Ala Gly Thr Ser Leu Ser Asp Asn Thr Thr Ser Val Ser Asn Ala Val

755 760 765

aac ctt cgc tgt ctg gct cgc gca gac gag ccg ctc ttg aca cgg ctc 2352

Asn Leu Arg Cys Leu Ala Arg Ala Asp Glu Pro Leu Leu Thr Arg Leu

770 775 780

gag cgc ttt caa ctg ctc tcg acg ctc gca tct cgc gtt gca ggc aca 2400

Glu Arg Phe Gln Leu Leu Ser Thr Leu Ala Ser Arg Val Ala Gly Thr

785 790 795 800

att ggc agg acc gaa cat tct cca cct agc aat ctc gag agt ctc ctc 2448

Ile Gly Arg Thr Glu His Ser Pro Pro Ser Asn Leu Glu Ser Leu Leu

805 810 815

gga ttc gac gcg ctc agc ttt gcc gac gcg ttt tca agc tca cat gcc 2496

Gly Phe Asp Ala Leu Ser Phe Ala Asp Ala Phe Ser Ser Ser His Ala

820 825 830

aat ctc ttt ggc gga agt tgg gtg cgg tgc ctc gat ggc ctc aag att 2544

Asn Leu Phe Gly Gly Ser Trp Val Arg Cys Leu Asp Gly Leu Lys Ile

835 840 845

tat gcc atc gct gca gac tta gat gca gaa gac tgg cgg cgc ttc gca 2592

Tyr Ala Ile Ala Ala Asp Leu Asp Ala Glu Asp Trp Arg Arg Phe Ala

850 855 860

gat gaa gga tac aaa tgg tcg cct cga ggc aaa ggg cgc ttg atc gcc 2640

Asp Glu Gly Tyr Lys Trp Ser Pro Arg Gly Lys Gly Arg Leu Ile Ala

865 870 875 880

cta gag gaa gac gat gtt ctg ttc att ccg cct ggc ctg cgg gcc ata 2688

Leu Glu Glu Asp Asp Val Leu Phe Ile Pro Pro Gly Leu Arg Ala Ile

885 890 895

cat gcc agc ttc acg cca gag ccc tgt ttg atg gaa ggc ggt atg ctg 2736

His Ala Ser Phe Thr Pro Glu Pro Cys Leu Met Glu Gly Gly Met Leu

900 905 910

tgg gac gaa tgc gcc atc cct gag atc tta gac gag ctg ctc tgg att 2784

Trp Asp Glu Cys Ala Ile Pro Glu Ile Leu Asp Glu Leu Leu Trp Ile

915 920 925

gca cga cac cag gca ggc act gtc cag cct ctc gaa ttt cag ctt tca 2832

Ala Arg His Gln Ala Gly Thr Val Gln Pro Leu Glu Phe Gln Leu Ser

930 935 940

agt ctg att gat gcg ctg gag cag tgg ttg aat gag aat aac cac att 2880

Ser Leu Ile Asp Ala Leu Glu Gln Trp Leu Asn Glu Asn Asn His Ile

945 950 955 960

aac cag tcg tcg cca tca cac act gca gct gaa gag cgt cag acg ctc 2928

Asn Gln Ser Ser Pro Ser His Thr Ala Ala Glu Glu Arg Gln Thr Leu

965 970 975

aag gct agc att cag tcg ctt cgc gac tgt tta agc ggc aga tca gcg 2976

Lys Ala Ser Ile Gln Ser Leu Arg Asp Cys Leu Ser Gly Arg Ser Ala

980 985 990

gct ttc cca tct tga 2991

Ala Phe Pro Ser

995

<210> 45

<211> 996

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 45

Met Ala Leu Gln Glu Arg Arg Ala Ala Val Thr Ser Ser Asp Ile Leu

1 5 10 15

Ser Ala His Ala Ile Ser Ser Pro Ala Leu Ala Ala Ala Ala Ile Asn

20 25 30

Phe Ala Ala Ser Phe His Arg Asp Ala Arg Thr Cys Cys Ser Ala His

35 40 45

Glu Arg Ser Gln Leu Gln Lys Val Tyr Arg Asp Lys Ile Leu Ala Asn

50 55 60

Asp Lys Phe Thr Ala Asn Ile Ala Ala Ala Phe Leu Ser Val Leu Gly

65 70 75 80

Pro Asn Ala Gly Arg Asn Asp Ala Gly Ala Glu Arg Glu Arg Trp Gly

85 90 95

Asp Phe Asp Arg Leu Ala Gln Arg Gly Lys Asn Met Arg Asp Arg Glu

100 105 110

Ser Gln His Leu Gln His Gln Ser Gly Ile Ile Ala Ala Trp Gly Pro

115 120 125

Arg Cys Phe Glu Tyr Tyr Gly Trp His Val Leu Pro Leu Pro Leu Leu

130 135 140

Arg Gln Val His Asp Leu Ala Val Leu Ile Pro Ser Trp Asp Asp Ala

145 150 155 160

Val Glu Leu Leu Asn Ser Arg Met Leu Leu Arg His Glu Leu Arg Val

165 170 175

Leu His Gly Asn Asn Lys Ala Leu Arg Ile Gly Glu His Ser Ala Ala

180 185 190

Ser Lys Val Gln Asp Ser Arg Ser Pro Val Glu Arg Thr Asp Ile Val

195 200 205

Ala Ala Leu Asp Trp Ala Arg Ala Asn Ala Thr Ser Ala Ala Ala Arg

210 215 220

Gln Ala Val Lys Glu Ala Ala Gln Gly Met Asn Gly Thr Pro Ile Asn

225 230 235 240

Thr Phe Gly Leu Lys Arg Asp Cys Tyr Gly Met Val Val Pro Ser Val

245 250 255

Gly Pro Tyr Asp Pro Asp Gly Asp Asp Asp Asn Asp Glu Asp Val Val

260 265 270

Asp Val Ser Pro Arg Pro Ala Lys His Ile Lys Leu Ser Ala Ala Glu

275 280 285

Pro Leu Arg Leu Met Phe Pro Gly Ser Leu Ser His Val Gln Ala Cys

290 295 300

Gln Arg His Asp Thr Asp Gly Glu Lys Ala Ser Thr Ala Pro Ile Arg

305 310 315 320

Ser Asn Lys Leu Ser Gln Ser Lys Gln Pro Glu Leu Asp Thr Ala Ala

325 330 335

Glu Ser Leu Arg Thr Arg His Ile His Asn Glu Arg Ile Asn Glu Pro

340 345 350

Leu Asp Glu Val Ser Asp Cys Ser Leu Ser Leu Gln Thr Ile Ala Val

355 360 365

Gly Gly Gly Ser Ala Gln Glu Glu Thr Pro Asp Gln Asp Val Glu His

370 375 380

Ala His Pro Glu Val Glu Ile Thr Ser Ala Ile Ser Ser Glu Leu Arg

385 390 395 400

Lys Val Asp Glu Arg Thr Asp Gly Ile Arg Ile Gly Arg Val Ile Met

405 410 415

Arg Arg Ser His Cys Met Val Arg Glu Gln Asp Asn Gln Thr Asn Glu

420 425 430

Glu Gly Thr Gly Glu Val Gln Ser Gln Arg Asp Arg Arg Ala Arg Asp

435 440 445

Leu Gly Lys Asp Met Glu Thr Asp Met Asp Ile Asp Ser Gln Leu Glu

450 455 460

Glu Met Leu Asp Ile His Ala Leu Glu Ala Gln Arg Asn His Glu Glu

465 470 475 480

Met Ser Asp Gly Glu Asp Val Val Ala Gly Val Ala Gly Pro Gly Thr

485 490 495

Pro Thr His Arg Ala Ala Glu Glu Gly Gly Cys Arg Glu Lys Glu Ala

500 505 510

Glu Asn Ala Lys Thr Asp Glu Glu Gln Val Gln Asp Lys Ala Ala Leu

515 520 525

Asp Gln Ala Gly Asn Thr Asn Thr Asn Arg Glu Val Glu Asn Ala Ala

530 535 540

Pro Lys Ala His Ser Gln Glu Gly Ala Leu Arg Ala Ser Arg Thr Gly

545 550 555 560

Thr Ile Val Glu Arg Thr Val Glu Leu His Ser Thr His Ser Ile His

565 570 575

Gln Arg Ala Ser Val Asn Thr Thr Ala Pro Thr Val Ala Arg Ser Ser

580 585 590

Asp Ser Asp Asp Ser Asp Ser Leu His Ser Pro Thr Ala Leu Gln Asn

595 600 605

Leu Gln Ala Tyr Ile Asp Thr Arg Thr His Gln Leu Thr Gln Val Leu

610 615 620

Ser Gln Leu Asn Ser Thr Pro Asp Val Arg His His Ala Gln Leu Gln

625 630 635 640

Leu Asp Trp Leu Ser Pro Gln Arg Trp Ala Ser Val Tyr Val Glu Pro

645 650 655

Glu His His Met Gly Ala Thr Ser Ser Ala Ser Ser Asp Ser Ala Asp

660 665 670

Ile Trp Cys Leu Asp Trp Asp Thr Phe His Gln Tyr Ala Asp Ser Asn

675 680 685

His Val Phe Arg Arg Pro Val Val Ile Lys Gln Lys Phe Gln Asp Ser

690 695 700

Gly Met Tyr Glu Val Asp Arg Tyr Val Asp Met Leu Trp Gln Arg Phe

705 710 715 720

Pro Glu Gln His Ile Glu Val Gln Asn Ser Ile Thr Gly Thr Ser Arg

725 730 735

Leu Met Ser Met Ala Glu Tyr Cys Ser Thr Ala Leu Thr Val Thr Glu

740 745 750

Ala Gly Thr Ser Leu Ser Asp Asn Thr Thr Ser Val Ser Asn Ala Val

755 760 765

Asn Leu Arg Cys Leu Ala Arg Ala Asp Glu Pro Leu Leu Thr Arg Leu

770 775 780

Glu Arg Phe Gln Leu Leu Ser Thr Leu Ala Ser Arg Val Ala Gly Thr

785 790 795 800

Ile Gly Arg Thr Glu His Ser Pro Pro Ser Asn Leu Glu Ser Leu Leu

805 810 815

Gly Phe Asp Ala Leu Ser Phe Ala Asp Ala Phe Ser Ser Ser His Ala

820 825 830

Asn Leu Phe Gly Gly Ser Trp Val Arg Cys Leu Asp Gly Leu Lys Ile

835 840 845

Tyr Ala Ile Ala Ala Asp Leu Asp Ala Glu Asp Trp Arg Arg Phe Ala

850 855 860

Asp Glu Gly Tyr Lys Trp Ser Pro Arg Gly Lys Gly Arg Leu Ile Ala

865 870 875 880

Leu Glu Glu Asp Asp Val Leu Phe Ile Pro Pro Gly Leu Arg Ala Ile

885 890 895

His Ala Ser Phe Thr Pro Glu Pro Cys Leu Met Glu Gly Gly Met Leu

900 905 910

Trp Asp Glu Cys Ala Ile Pro Glu Ile Leu Asp Glu Leu Leu Trp Ile

915 920 925

Ala Arg His Gln Ala Gly Thr Val Gln Pro Leu Glu Phe Gln Leu Ser

930 935 940

Ser Leu Ile Asp Ala Leu Glu Gln Trp Leu Asn Glu Asn Asn His Ile

945 950 955 960

Asn Gln Ser Ser Pro Ser His Thr Ala Ala Glu Glu Arg Gln Thr Leu

965 970 975

Lys Ala Ser Ile Gln Ser Leu Arg Asp Cys Leu Ser Gly Arg Ser Ala

980 985 990

Ala Phe Pro Ser

995

<210> 46

<211> 234

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(234)

<400> 46

atg tca aac aag aag aac gag ggc ctt gag aag gga ggc aat ggg tcg 48

Met Ser Asn Lys Lys Asn Glu Gly Leu Glu Lys Gly Gly Asn Gly Ser

1 5 10 15

gct gag cac gag agc ttt ctg ccc aag tcg gcg ctt cac tac cgc gct 96

Ala Glu His Glu Ser Phe Leu Pro Lys Ser Ala Leu His Tyr Arg Ala

20 25 30

cgc gtc gat ggc ggc aca agc ggc ctt ctt gcg cgg ctc gac aat agt 144

Arg Val Asp Gly Gly Thr Ser Gly Leu Leu Ala Arg Leu Asp Asn Ser

35 40 45

ccc ggc gct gct gtc ttg gct tat tgc ttc tcc tcg gtc agc acc ctt 192

Pro Gly Ala Ala Val Leu Ala Tyr Cys Phe Ser Ser Val Ser Thr Leu

50 55 60

gga tat gtt ccg gac tgc gag gat aac ctt tgc ggc tcc taa 234

Gly Tyr Val Pro Asp Cys Glu Asp Asn Leu Cys Gly Ser

65 70 75

<210> 47

<211> 77

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 47

Met Ser Asn Lys Lys Asn Glu Gly Leu Glu Lys Gly Gly Asn Gly Ser

1 5 10 15

Ala Glu His Glu Ser Phe Leu Pro Lys Ser Ala Leu His Tyr Arg Ala

20 25 30

Arg Val Asp Gly Gly Thr Ser Gly Leu Leu Ala Arg Leu Asp Asn Ser

35 40 45

Pro Gly Ala Ala Val Leu Ala Tyr Cys Phe Ser Ser Val Ser Thr Leu

50 55 60

Gly Tyr Val Pro Asp Cys Glu Asp Asn Leu Cys Gly Ser

65 70 75

<210> 48

<211> 4017

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(4017)

<400> 48

atg agt gct atc gag ctg ccg ccg ctg cgc tcg cgg tct gaa gaa gca 48

Met Ser Ala Ile Glu Leu Pro Pro Leu Arg Ser Arg Ser Glu Glu Ala

1 5 10 15

gcg agg gca gaa cac aat gcg cag aca ctc gca cac gaa aat gca aat 96

Ala Arg Ala Glu His Asn Ala Gln Thr Leu Ala His Glu Asn Ala Asn

20 25 30

atc gcg ggc tat gat gag agc ccg gca gtc caa caa gtc gag acc gat 144

Ile Ala Gly Tyr Asp Glu Ser Pro Ala Val Gln Gln Val Glu Thr Asp

35 40 45

gct cca gag act aaa gga gcc ccg cag gct tct ttc aag aat tac ttt 192

Ala Pro Glu Thr Lys Gly Ala Pro Gln Ala Ser Phe Lys Asn Tyr Phe

50 55 60

cgt gtc ttt tca tat ggg aca aag ctt gac tac ttt tta att tcg cta 240

Arg Val Phe Ser Tyr Gly Thr Lys Leu Asp Tyr Phe Leu Ile Ser Leu

65 70 75 80

tgt tgc ttt acg tct att gga gca ggt act gcg atg ccg ctg atg aac 288

Cys Cys Phe Thr Ser Ile Gly Ala Gly Thr Ala Met Pro Leu Met Asn

85 90 95

att gtc ttt ggc aag ctc gta gga aat ttt aca gac tac ttc atc cca 336

Ile Val Phe Gly Lys Leu Val Gly Asn Phe Thr Asp Tyr Phe Ile Pro

100 105 110

gga tca aat gtc acc cga caa gaa ttc gag gca gag att aac aaa cta 384

Gly Ser Asn Val Thr Arg Gln Glu Phe Glu Ala Glu Ile Asn Lys Leu

115 120 125

gcc ctc tat atc ttc tac ctc ttc ata ggc aag ttt gcc atg tcg tac 432

Ala Leu Tyr Ile Phe Tyr Leu Phe Ile Gly Lys Phe Ala Met Ser Tyr

130 135 140

att tcc atg ctc gca att cga atc agc ggt atg aga ata tcg gct gcg 480

Ile Ser Met Leu Ala Ile Arg Ile Ser Gly Met Arg Ile Ser Ala Ala

145 150 155 160

ctt cgc ctg gca tac ctg cgt gca ctc ttc gcc cag cca gtg agc gtt 528

Leu Arg Leu Ala Tyr Leu Arg Ala Leu Phe Ala Gln Pro Val Ser Val

165 170 175

atc gac acc gtc agt ccc ggc aag gtt gcc aat cgc atc acg acg tca 576

Ile Asp Thr Val Ser Pro Gly Lys Val Ala Asn Arg Ile Thr Thr Ser

180 185 190

tcg aat atc gtc cag ctt gct atc tcg cag cat ttt gca acc ctg ttt 624

Ser Asn Ile Val Gln Leu Ala Ile Ser Gln His Phe Ala Thr Leu Phe

195 200 205

cag tct ctt gcc ttc acc gtc gga tta tac gtg gtg gcg tta gta aaa 672

Gln Ser Leu Ala Phe Thr Val Gly Leu Tyr Val Val Ala Leu Val Lys

210 215 220

ggg tgg aag ttg acg ctg atc gcc tcg acg ggt ctc cct ttc atc cta 720

Gly Trp Lys Leu Thr Leu Ile Ala Ser Thr Gly Leu Pro Phe Ile Leu

225 230 235 240

atc gta tac ggc gcc atg ttc ccg ccc ttt ctc cgg atc cac cag atc 768

Ile Val Tyr Gly Ala Met Phe Pro Pro Phe Leu Arg Ile His Gln Ile

245 250 255

acc gac aag ttc caa gag gaa gca tcg gct atg gcg tat gaa atg ttc 816

Thr Asp Lys Phe Gln Glu Glu Ala Ser Ala Met Ala Tyr Glu Met Phe

260 265 270

tcc tcc att agg atg att gtc gcc ttt ggc acc gag tcg aga ctt gct 864

Ser Ser Ile Arg Met Ile Val Ala Phe Gly Thr Glu Ser Arg Leu Ala

275 280 285

aag cag cac gga gtc atg ctc tcc aaa gct gca agc aat gag aaa aga 912

Lys Gln His Gly Val Met Leu Ser Lys Ala Ala Ser Asn Glu Lys Arg

290 295 300

gct gcg ccg tta atg ggc ttg acc atg tct ccg gct atg gtg gcc atg 960

Ala Ala Pro Leu Met Gly Leu Thr Met Ser Pro Ala Met Val Ala Met

305 310 315 320

tac ggt atc ttc ggt atc acc ttc tgg ttc gga atc aag gaa tat aca 1008

Tyr Gly Ile Phe Gly Ile Thr Phe Trp Phe Gly Ile Lys Glu Tyr Thr

325 330 335

aaa ggg aga atc tca agc gtc ggc gac atc acc gtt gtg ctc ttc tca 1056

Lys Gly Arg Ile Ser Ser Val Gly Asp Ile Thr Val Val Leu Phe Ser

340 345 350

gtc atg atg gcc gta atg aat att ggg cga gtc gcg tct ccg att ata 1104

Val Met Met Ala Val Met Asn Ile Gly Arg Val Ala Ser Pro Ile Ile

355 360 365

tcc atc gca aaa gcc gcg act gct gcg acc gag ctc ttt gtc aca atc 1152

Ser Ile Ala Lys Ala Ala Thr Ala Ala Thr Glu Leu Phe Val Thr Ile

370 375 380

gac gct tcg ttc cac gat aca tct ggt gtc atg gag ccc gag gtt aca 1200

Asp Ala Ser Phe His Asp Thr Ser Gly Val Met Glu Pro Glu Val Thr

385 390 395 400

ggt aat gct gct atc act ttc atc aat gtt gct ttt tcg tac ccc agc 1248

Gly Asn Ala Ala Ile Thr Phe Ile Asn Val Ala Phe Ser Tyr Pro Ser

405 410 415

cgg ccg ggt gtc cca att ctc aag gga ctt gat ttg aca att act gct 1296

Arg Pro Gly Val Pro Ile Leu Lys Gly Leu Asp Leu Thr Ile Thr Ala

420 425 430

ggc aaa gtc act gcc att gta ggt cca tcg ggg tcc ggg aaa agc acg 1344

Gly Lys Val Thr Ala Ile Val Gly Pro Ser Gly Ser Gly Lys Ser Thr

435 440 445

att gtt ggc ctt atc caa cga tgg tac gac ctt ctc ggc aca aca gct 1392

Ile Val Gly Leu Ile Gln Arg Trp Tyr Asp Leu Leu Gly Thr Thr Ala

450 455 460

act gct aag aaa atc gac gag aca gag att cct tca tca tcc act atg 1440

Thr Ala Lys Lys Ile Asp Glu Thr Glu Ile Pro Ser Ser Ser Thr Met

465 470 475 480

gcg tcc agc cca ata gaa gca gtc tat gac aat aca gac aag aaa tcc 1488

Ala Ser Ser Pro Ile Glu Ala Val Tyr Asp Asn Thr Asp Lys Lys Ser

485 490 495

aaa aag ggg aag gcc ggg gaa gaa gaa gaa cca gaa caa gat ctc ggg 1536

Lys Lys Gly Lys Ala Gly Glu Glu Glu Glu Pro Glu Gln Asp Leu Gly

500 505 510

cca aat acg tgc act ggc tcg ttg agt gtt ggt aga aca aat ctt cgt 1584

Pro Asn Thr Cys Thr Gly Ser Leu Ser Val Gly Arg Thr Asn Leu Arg

515 520 525

aat gtg gat gta agg tgg tgg cgt tcg caa atc ggc atg gtc cag cag 1632

Asn Val Asp Val Arg Trp Trp Arg Ser Gln Ile Gly Met Val Gln Gln

530 535 540

gag cct ttc ctg ttc aat gat aca ata tac aac aat att gtg ttt gga 1680

Glu Pro Phe Leu Phe Asn Asp Thr Ile Tyr Asn Asn Ile Val Phe Gly

545 550 555 560

ctc tgc ggg acc cgt tat gaa gga ctg tcc aaa gat gaa aag aaa ata 1728

Leu Cys Gly Thr Arg Tyr Glu Gly Leu Ser Lys Asp Glu Lys Lys Ile

565 570 575

atg gtc gat gag gcg tgt cgc gag gct tgc gcg gag gag ttt atc tcg 1776

Met Val Asp Glu Ala Cys Arg Glu Ala Cys Ala Glu Glu Phe Ile Ser

580 585 590

cgg ctc cca caa ggg ttg gac acg ctt gtg ggc gag agc ggc atc aaa 1824

Arg Leu Pro Gln Gly Leu Asp Thr Leu Val Gly Glu Ser Gly Ile Lys

595 600 605

ctt tct ggt ggc cag cgt cag cgt atc gcc att gcc agg agt att atc 1872

Leu Ser Gly Gly Gln Arg Gln Arg Ile Ala Ile Ala Arg Ser Ile Ile

610 615 620

aaa cga ccg cct att ctc att cta gac gag gca acg agt gcc atc gat 1920

Lys Arg Pro Pro Ile Leu Ile Leu Asp Glu Ala Thr Ser Ala Ile Asp

625 630 635 640

gtc aga acg gag cga att gtt caa gaa gcg ctt gat cgt gtt tct aag 1968

Val Arg Thr Glu Arg Ile Val Gln Glu Ala Leu Asp Arg Val Ser Lys

645 650 655

aac cgt acc acg att gtc atc gca cat cgc cta tcc aca atc aaa cgg 2016

Asn Arg Thr Thr Ile Val Ile Ala His Arg Leu Ser Thr Ile Lys Arg

660 665 670

gcg gac agc ata gtc gtc tta cgg cag ggc cag ctg gtt gag caa ggc 2064

Ala Asp Ser Ile Val Val Leu Arg Gln Gly Gln Leu Val Glu Gln Gly

675 680 685

acg cat gaa gag ctg ctg aaa aac gga gat ggg gtc tat tac ggc tta 2112

Thr His Glu Glu Leu Leu Lys Asn Gly Asp Gly Val Tyr Tyr Gly Leu

690 695 700

gtt cat gcc caa gag ctg gaa atg gac gct gaa gac gat gat gac cac 2160

Val His Ala Gln Glu Leu Glu Met Asp Ala Glu Asp Asp Asp Asp His

705 710 715 720

agc tca agc tta gag aac atc aaa atg aac gac act aag gag gac act 2208

Ser Ser Ser Leu Glu Asn Ile Lys Met Asn Asp Thr Lys Glu Asp Thr

725 730 735

gct agt agc gga ttc gag gga cac gct tct aga gaa gat tca aca tat 2256

Ala Ser Ser Gly Phe Glu Gly His Ala Ser Arg Glu Asp Ser Thr Tyr

740 745 750

cag aat gta ggt cta ctt cac agt ctc ggt cga ctt gtt gta gag caa 2304

Gln Asn Val Gly Leu Leu His Ser Leu Gly Arg Leu Val Val Glu Gln

755 760 765

cgt cac cat tgg atc ctc tac agc gtt tgc tgc ata ggc ata ctc gga 2352

Arg His His Trp Ile Leu Tyr Ser Val Cys Cys Ile Gly Ile Leu Gly

770 775 780

gcc ggc gca gtc tac cca ctc caa gcg tac att ttc gca agg att atc 2400

Ala Gly Ala Val Tyr Pro Leu Gln Ala Tyr Ile Phe Ala Arg Ile Ile

785 790 795 800

aac gtc ttc aca ctt aca ggt ccc gag ctc gtc aaa caa ggc aac ttc 2448

Asn Val Phe Thr Leu Thr Gly Pro Glu Leu Val Lys Gln Gly Asn Phe

805 810 815

tgg gca ggc atg ttc ggc gta ctt gcg ggt ggg gtt gga ctg tcg tac 2496

Trp Ala Gly Met Phe Gly Val Leu Ala Gly Gly Val Gly Leu Ser Tyr

820 825 830

tat ctg ctt ggt gct gcc tca cat cta att tct gtc gaa tta aca cgc 2544

Tyr Leu Leu Gly Ala Ala Ser His Leu Ile Ser Val Glu Leu Thr Arg

835 840 845

aag tat cga tca gaa tac ctc agc aac atg atc cga aaa cca atc ctc 2592

Lys Tyr Arg Ser Glu Tyr Leu Ser Asn Met Ile Arg Lys Pro Ile Leu

850 855 860

ttt ttt gac gat aaa gtt cac agc cca ggc tct ctt acg tca aga ctg 2640

Phe Phe Asp Asp Lys Val His Ser Pro Gly Ser Leu Thr Ser Arg Leu

865 870 875 880

agc tcg gac agt caa cag gtc cag cag ttg ttg tcg atg gag atg agc 2688

Ser Ser Asp Ser Gln Gln Val Gln Gln Leu Leu Ser Met Glu Met Ser

885 890 895

atg gcg ctc att gcc tgc acc aac ctt ctc gga tgt aca att atc gcc 2736

Met Ala Leu Ile Ala Cys Thr Asn Leu Leu Gly Cys Thr Ile Ile Ala

900 905 910

ttc gtt tac ggc tgg aag ctt tcc ctt gtt ggt tta ttt gct gcc ttg 2784

Phe Val Tyr Gly Trp Lys Leu Ser Leu Val Gly Leu Phe Ala Ala Leu

915 920 925

cct ctc att ctt ggt gcc gga ctc gtg cgc acg cgt ctc gag ata caa 2832

Pro Leu Ile Leu Gly Ala Gly Leu Val Arg Thr Arg Leu Glu Ile Gln

930 935 940

ctc gag gct gag aac gca aaa gtt ttc gag aac agc agc cag ttt gcc 2880

Leu Glu Ala Glu Asn Ala Lys Val Phe Glu Asn Ser Ser Gln Phe Ala

945 950 955 960

aca gaa gcg gtg gca ggt ttc cgc act gtg cta agt ctg ctc atg gag 2928

Thr Glu Ala Val Ala Gly Phe Arg Thr Val Leu Ser Leu Leu Met Glu

965 970 975

ccg atg att aga agc cgc tac gac aag ttg ctc aag ggc cac gtt gtg 2976

Pro Met Ile Arg Ser Arg Tyr Asp Lys Leu Leu Lys Gly His Val Val

980 985 990

gaa gct ttg gcc aag gca aaa tat ggt acc atc att ttc gct gca agt 3024

Glu Ala Leu Ala Lys Ala Lys Tyr Gly Thr Ile Ile Phe Ala Ala Ser

995 1000 1005

gac agt ctt gag ctt gca tgt atg tct ctg acc ttc tgg tac ggc 3069

Asp Ser Leu Glu Leu Ala Cys Met Ser Leu Thr Phe Trp Tyr Gly

1010 1015 1020

gga aaa ctc ctt gcg tct cgt gaa tat gat ctc att cag ttc ttc 3114

Gly Lys Leu Leu Ala Ser Arg Glu Tyr Asp Leu Ile Gln Phe Phe

1025 1030 1035

att gtc tac acg gcc atc att caa ggc gct acg gca gca gga atc 3159

Ile Val Tyr Thr Ala Ile Ile Gln Gly Ala Thr Ala Ala Gly Ile

1040 1045 1050

tgg ttc tct ttt act cca agc atg gct caa gcg aca ggt gct gca 3204

Trp Phe Ser Phe Thr Pro Ser Met Ala Gln Ala Thr Gly Ala Ala

1055 1060 1065

aac cga atc ctt agc atg cgg ccg aca tcg acg gat cca tca tct 3249

Asn Arg Ile Leu Ser Met Arg Pro Thr Ser Thr Asp Pro Ser Ser

1070 1075 1080

tac tcg cct ctt cca tgc tca gat gag gga gtg ggc att gaa ttt 3294

Tyr Ser Pro Leu Pro Cys Ser Asp Glu Gly Val Gly Ile Glu Phe

1085 1090 1095

caa cac gtc tcc ttc aaa tac cag tct cga gac gtg ccc gtt ctt 3339

Gln His Val Ser Phe Lys Tyr Gln Ser Arg Asp Val Pro Val Leu

1100 1105 1110

tcc aac ctc aat ctg caa atc cta ccg ggt cag gtt gct gcg tta 3384

Ser Asn Leu Asn Leu Gln Ile Leu Pro Gly Gln Val Ala Ala Leu

1115 1120 1125

gta ggc agt agt ggc tgt ggt aaa tca aca aca ctg tct ctt ctc 3429

Val Gly Ser Ser Gly Cys Gly Lys Ser Thr Thr Leu Ser Leu Leu

1130 1135 1140

gaa cgc ttc tac gat gcg agt tcg ggc cat att cta tac aac ggg 3474

Glu Arg Phe Tyr Asp Ala Ser Ser Gly His Ile Leu Tyr Asn Gly

1145 1150 1155

caa gac atc acc acg ttc agc ccg gca gag tac cgg aaa caa atg 3519

Gln Asp Ile Thr Thr Phe Ser Pro Ala Glu Tyr Arg Lys Gln Met

1160 1165 1170

agc ctg gtg agc caa gag ccc acg ctc tac caa ggc agc att cga 3564

Ser Leu Val Ser Gln Glu Pro Thr Leu Tyr Gln Gly Ser Ile Arg

1175 1180 1185

gaa aac ata tct ctg agt gta gag tct gca tcc gac gac gac atc 3609

Glu Asn Ile Ser Leu Ser Val Glu Ser Ala Ser Asp Asp Asp Ile

1190 1195 1200

aaa cag gcc tgc cgt gat gcg caa att cat gac ttc atc acc tcg 3654

Lys Gln Ala Cys Arg Asp Ala Gln Ile His Asp Phe Ile Thr Ser

1205 1210 1215

ctt cca gaa ggc tac gag acg cgc ttg gga ccg aaa gga atg tct 3699

Leu Pro Glu Gly Tyr Glu Thr Arg Leu Gly Pro Lys Gly Met Ser

1220 1225 1230

ctc tca ggt ggt caa aga cag cga atc tct ctt gcc agg gcg ctg 3744

Leu Ser Gly Gly Gln Arg Gln Arg Ile Ser Leu Ala Arg Ala Leu

1235 1240 1245

ttg cgc aaa cca aaa atc cta ctc ctc gat gaa gca acc agc tcg 3789

Leu Arg Lys Pro Lys Ile Leu Leu Leu Asp Glu Ala Thr Ser Ser

1250 1255 1260

cta gat tca gag agc gag aaa tac gtc cag gaa gct atc gag cga 3834

Leu Asp Ser Glu Ser Glu Lys Tyr Val Gln Glu Ala Ile Glu Arg

1265 1270 1275

gct gca agc gag ggt gac aga acc gtc ata att gtt gcg cat agg 3879

Ala Ala Ser Glu Gly Asp Arg Thr Val Ile Ile Val Ala His Arg

1280 1285 1290

ctg gct aca att cag aag gcg gat gtt atc ttt gta ctg ggc agt 3924

Leu Ala Thr Ile Gln Lys Ala Asp Val Ile Phe Val Leu Gly Ser

1295 1300 1305

gga aag gtg cta gag aag ggg gat cat cag gca ctg ctc cgg aaa 3969

Gly Lys Val Leu Glu Lys Gly Asp His Gln Ala Leu Leu Arg Lys

1310 1315 1320

aag ggc gtg tac tgg cag atg tgt caa gcc cag gcc ctc aat cgc 4014

Lys Gly Val Tyr Trp Gln Met Cys Gln Ala Gln Ala Leu Asn Arg

1325 1330 1335

tga 4017

<210> 49

<211> 1338

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 49

Met Ser Ala Ile Glu Leu Pro Pro Leu Arg Ser Arg Ser Glu Glu Ala

1 5 10 15

Ala Arg Ala Glu His Asn Ala Gln Thr Leu Ala His Glu Asn Ala Asn

20 25 30

Ile Ala Gly Tyr Asp Glu Ser Pro Ala Val Gln Gln Val Glu Thr Asp

35 40 45

Ala Pro Glu Thr Lys Gly Ala Pro Gln Ala Ser Phe Lys Asn Tyr Phe

50 55 60

Arg Val Phe Ser Tyr Gly Thr Lys Leu Asp Tyr Phe Leu Ile Ser Leu

65 70 75 80

Cys Cys Phe Thr Ser Ile Gly Ala Gly Thr Ala Met Pro Leu Met Asn

85 90 95

Ile Val Phe Gly Lys Leu Val Gly Asn Phe Thr Asp Tyr Phe Ile Pro

100 105 110

Gly Ser Asn Val Thr Arg Gln Glu Phe Glu Ala Glu Ile Asn Lys Leu

115 120 125

Ala Leu Tyr Ile Phe Tyr Leu Phe Ile Gly Lys Phe Ala Met Ser Tyr

130 135 140

Ile Ser Met Leu Ala Ile Arg Ile Ser Gly Met Arg Ile Ser Ala Ala

145 150 155 160

Leu Arg Leu Ala Tyr Leu Arg Ala Leu Phe Ala Gln Pro Val Ser Val

165 170 175

Ile Asp Thr Val Ser Pro Gly Lys Val Ala Asn Arg Ile Thr Thr Ser

180 185 190

Ser Asn Ile Val Gln Leu Ala Ile Ser Gln His Phe Ala Thr Leu Phe

195 200 205

Gln Ser Leu Ala Phe Thr Val Gly Leu Tyr Val Val Ala Leu Val Lys

210 215 220

Gly Trp Lys Leu Thr Leu Ile Ala Ser Thr Gly Leu Pro Phe Ile Leu

225 230 235 240

Ile Val Tyr Gly Ala Met Phe Pro Pro Phe Leu Arg Ile His Gln Ile

245 250 255

Thr Asp Lys Phe Gln Glu Glu Ala Ser Ala Met Ala Tyr Glu Met Phe

260 265 270

Ser Ser Ile Arg Met Ile Val Ala Phe Gly Thr Glu Ser Arg Leu Ala

275 280 285

Lys Gln His Gly Val Met Leu Ser Lys Ala Ala Ser Asn Glu Lys Arg

290 295 300

Ala Ala Pro Leu Met Gly Leu Thr Met Ser Pro Ala Met Val Ala Met

305 310 315 320

Tyr Gly Ile Phe Gly Ile Thr Phe Trp Phe Gly Ile Lys Glu Tyr Thr

325 330 335

Lys Gly Arg Ile Ser Ser Val Gly Asp Ile Thr Val Val Leu Phe Ser

340 345 350

Val Met Met Ala Val Met Asn Ile Gly Arg Val Ala Ser Pro Ile Ile

355 360 365

Ser Ile Ala Lys Ala Ala Thr Ala Ala Thr Glu Leu Phe Val Thr Ile

370 375 380

Asp Ala Ser Phe His Asp Thr Ser Gly Val Met Glu Pro Glu Val Thr

385 390 395 400

Gly Asn Ala Ala Ile Thr Phe Ile Asn Val Ala Phe Ser Tyr Pro Ser

405 410 415

Arg Pro Gly Val Pro Ile Leu Lys Gly Leu Asp Leu Thr Ile Thr Ala

420 425 430

Gly Lys Val Thr Ala Ile Val Gly Pro Ser Gly Ser Gly Lys Ser Thr

435 440 445

Ile Val Gly Leu Ile Gln Arg Trp Tyr Asp Leu Leu Gly Thr Thr Ala

450 455 460

Thr Ala Lys Lys Ile Asp Glu Thr Glu Ile Pro Ser Ser Ser Thr Met

465 470 475 480

Ala Ser Ser Pro Ile Glu Ala Val Tyr Asp Asn Thr Asp Lys Lys Ser

485 490 495

Lys Lys Gly Lys Ala Gly Glu Glu Glu Glu Pro Glu Gln Asp Leu Gly

500 505 510

Pro Asn Thr Cys Thr Gly Ser Leu Ser Val Gly Arg Thr Asn Leu Arg

515 520 525

Asn Val Asp Val Arg Trp Trp Arg Ser Gln Ile Gly Met Val Gln Gln

530 535 540

Glu Pro Phe Leu Phe Asn Asp Thr Ile Tyr Asn Asn Ile Val Phe Gly

545 550 555 560

Leu Cys Gly Thr Arg Tyr Glu Gly Leu Ser Lys Asp Glu Lys Lys Ile

565 570 575

Met Val Asp Glu Ala Cys Arg Glu Ala Cys Ala Glu Glu Phe Ile Ser

580 585 590

Arg Leu Pro Gln Gly Leu Asp Thr Leu Val Gly Glu Ser Gly Ile Lys

595 600 605

Leu Ser Gly Gly Gln Arg Gln Arg Ile Ala Ile Ala Arg Ser Ile Ile

610 615 620

Lys Arg Pro Pro Ile Leu Ile Leu Asp Glu Ala Thr Ser Ala Ile Asp

625 630 635 640

Val Arg Thr Glu Arg Ile Val Gln Glu Ala Leu Asp Arg Val Ser Lys

645 650 655

Asn Arg Thr Thr Ile Val Ile Ala His Arg Leu Ser Thr Ile Lys Arg

660 665 670

Ala Asp Ser Ile Val Val Leu Arg Gln Gly Gln Leu Val Glu Gln Gly

675 680 685

Thr His Glu Glu Leu Leu Lys Asn Gly Asp Gly Val Tyr Tyr Gly Leu

690 695 700

Val His Ala Gln Glu Leu Glu Met Asp Ala Glu Asp Asp Asp Asp His

705 710 715 720

Ser Ser Ser Leu Glu Asn Ile Lys Met Asn Asp Thr Lys Glu Asp Thr

725 730 735

Ala Ser Ser Gly Phe Glu Gly His Ala Ser Arg Glu Asp Ser Thr Tyr

740 745 750

Gln Asn Val Gly Leu Leu His Ser Leu Gly Arg Leu Val Val Glu Gln

755 760 765

Arg His His Trp Ile Leu Tyr Ser Val Cys Cys Ile Gly Ile Leu Gly

770 775 780

Ala Gly Ala Val Tyr Pro Leu Gln Ala Tyr Ile Phe Ala Arg Ile Ile

785 790 795 800

Asn Val Phe Thr Leu Thr Gly Pro Glu Leu Val Lys Gln Gly Asn Phe

805 810 815

Trp Ala Gly Met Phe Gly Val Leu Ala Gly Gly Val Gly Leu Ser Tyr

820 825 830

Tyr Leu Leu Gly Ala Ala Ser His Leu Ile Ser Val Glu Leu Thr Arg

835 840 845

Lys Tyr Arg Ser Glu Tyr Leu Ser Asn Met Ile Arg Lys Pro Ile Leu

850 855 860

Phe Phe Asp Asp Lys Val His Ser Pro Gly Ser Leu Thr Ser Arg Leu

865 870 875 880

Ser Ser Asp Ser Gln Gln Val Gln Gln Leu Leu Ser Met Glu Met Ser

885 890 895

Met Ala Leu Ile Ala Cys Thr Asn Leu Leu Gly Cys Thr Ile Ile Ala

900 905 910

Phe Val Tyr Gly Trp Lys Leu Ser Leu Val Gly Leu Phe Ala Ala Leu

915 920 925

Pro Leu Ile Leu Gly Ala Gly Leu Val Arg Thr Arg Leu Glu Ile Gln

930 935 940

Leu Glu Ala Glu Asn Ala Lys Val Phe Glu Asn Ser Ser Gln Phe Ala

945 950 955 960

Thr Glu Ala Val Ala Gly Phe Arg Thr Val Leu Ser Leu Leu Met Glu

965 970 975

Pro Met Ile Arg Ser Arg Tyr Asp Lys Leu Leu Lys Gly His Val Val

980 985 990

Glu Ala Leu Ala Lys Ala Lys Tyr Gly Thr Ile Ile Phe Ala Ala Ser

995 1000 1005

Asp Ser Leu Glu Leu Ala Cys Met Ser Leu Thr Phe Trp Tyr Gly

1010 1015 1020

Gly Lys Leu Leu Ala Ser Arg Glu Tyr Asp Leu Ile Gln Phe Phe

1025 1030 1035

Ile Val Tyr Thr Ala Ile Ile Gln Gly Ala Thr Ala Ala Gly Ile

1040 1045 1050

Trp Phe Ser Phe Thr Pro Ser Met Ala Gln Ala Thr Gly Ala Ala

1055 1060 1065

Asn Arg Ile Leu Ser Met Arg Pro Thr Ser Thr Asp Pro Ser Ser

1070 1075 1080

Tyr Ser Pro Leu Pro Cys Ser Asp Glu Gly Val Gly Ile Glu Phe

1085 1090 1095

Gln His Val Ser Phe Lys Tyr Gln Ser Arg Asp Val Pro Val Leu

1100 1105 1110

Ser Asn Leu Asn Leu Gln Ile Leu Pro Gly Gln Val Ala Ala Leu

1115 1120 1125

Val Gly Ser Ser Gly Cys Gly Lys Ser Thr Thr Leu Ser Leu Leu

1130 1135 1140

Glu Arg Phe Tyr Asp Ala Ser Ser Gly His Ile Leu Tyr Asn Gly

1145 1150 1155

Gln Asp Ile Thr Thr Phe Ser Pro Ala Glu Tyr Arg Lys Gln Met

1160 1165 1170

Ser Leu Val Ser Gln Glu Pro Thr Leu Tyr Gln Gly Ser Ile Arg

1175 1180 1185

Glu Asn Ile Ser Leu Ser Val Glu Ser Ala Ser Asp Asp Asp Ile

1190 1195 1200

Lys Gln Ala Cys Arg Asp Ala Gln Ile His Asp Phe Ile Thr Ser

1205 1210 1215

Leu Pro Glu Gly Tyr Glu Thr Arg Leu Gly Pro Lys Gly Met Ser

1220 1225 1230

Leu Ser Gly Gly Gln Arg Gln Arg Ile Ser Leu Ala Arg Ala Leu

1235 1240 1245

Leu Arg Lys Pro Lys Ile Leu Leu Leu Asp Glu Ala Thr Ser Ser

1250 1255 1260

Leu Asp Ser Glu Ser Glu Lys Tyr Val Gln Glu Ala Ile Glu Arg

1265 1270 1275

Ala Ala Ser Glu Gly Asp Arg Thr Val Ile Ile Val Ala His Arg

1280 1285 1290

Leu Ala Thr Ile Gln Lys Ala Asp Val Ile Phe Val Leu Gly Ser

1295 1300 1305

Gly Lys Val Leu Glu Lys Gly Asp His Gln Ala Leu Leu Arg Lys

1310 1315 1320

Lys Gly Val Tyr Trp Gln Met Cys Gln Ala Gln Ala Leu Asn Arg

1325 1330 1335

<210> 50

<211> 1047

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(1047)

<400> 50

atg aag ctc acc gtt ttc agt gca aaa ccc tac gat atc gaa tac ctg 48

Met Lys Leu Thr Val Phe Ser Ala Lys Pro Tyr Asp Ile Glu Tyr Leu

1 5 10 15

ggt ggc atc gct act aat caa aac tcc tcg cct gca att gag atc aac 96

Gly Gly Ile Ala Thr Asn Gln Asn Ser Ser Pro Ala Ile Glu Ile Asn

20 25 30

ttc ctg cat gtc ccg ctc tcc agc gag acg gcc gcg ttc gcg aac ggc 144

Phe Leu His Val Pro Leu Ser Ser Glu Thr Ala Ala Phe Ala Asn Gly

35 40 45

gct gat gcc gtc tgc gtc ttc gtt cac gat gtg ctt gac gcc aac gtc 192

Ala Asp Ala Val Cys Val Phe Val His Asp Val Leu Asp Ala Asn Val

50 55 60

ctc cgc gaa cta tac gcc gcc ggc gtg cgc gcc att ctc ttc cgc tgc 240

Leu Arg Glu Leu Tyr Ala Ala Gly Val Arg Ala Ile Leu Phe Arg Cys

65 70 75 80

tca ggg tat aac aat att gac cta agg gag gct gag cgc tta ggc ttc 288

Ser Gly Tyr Asn Asn Ile Asp Leu Arg Glu Ala Glu Arg Leu Gly Phe

85 90 95

ttc gtc gcc aac gtc cct tcg tac tcg ccg gag gca gtc gcc gag ttc 336

Phe Val Ala Asn Val Pro Ser Tyr Ser Pro Glu Ala Val Ala Glu Phe

100 105 110

gca gtc gcg ctc atc caa aca ctt aac cgg aag acg cac cgg gca tac 384

Ala Val Ala Leu Ile Gln Thr Leu Asn Arg Lys Thr His Arg Ala Tyr

115 120 125

aac cgc gtg cgg gac ggc aat ttc aac ctc gac ggc cta ctc gga cga 432

Asn Arg Val Arg Asp Gly Asn Phe Asn Leu Asp Gly Leu Leu Gly Arg

130 135 140

aca cta cac ggc aaa aca gtc ggc att gta ggg tca ggc cgg atc gga 480

Thr Leu His Gly Lys Thr Val Gly Ile Val Gly Ser Gly Arg Ile Gly

145 150 155 160

ctc gcc atg gcg cag atc gtt cag ggc ttc gga tgc aag ctg ttg gca 528

Leu Ala Met Ala Gln Ile Val Gln Gly Phe Gly Cys Lys Leu Leu Ala

165 170 175

tac gat cct cgg cct aca gaa gcc ttc aag aag tac ggc gaa tac gtg 576

Tyr Asp Pro Arg Pro Thr Glu Ala Phe Lys Lys Tyr Gly Glu Tyr Val

180 185 190

gat ctc gat acg ctg ctg tca caa tgc gac att gta agc tta cac tgc 624

Asp Leu Asp Thr Leu Leu Ser Gln Cys Asp Ile Val Ser Leu His Cys

195 200 205

ccg ctg atg gac tcg acg cag cac atc atc aac gac aca act gtc agc 672

Pro Leu Met Asp Ser Thr Gln His Ile Ile Asn Asp Thr Thr Val Ser

210 215 220

aaa atg aag cgc ggc gcg atg ctc gtc aac acg tcg cgt ggc ggg ctg 720

Lys Met Lys Arg Gly Ala Met Leu Val Asn Thr Ser Arg Gly Gly Leu

225 230 235 240

atc gac acg cag agc gtg atg aag gcg ctg aag agc aag cgt ctg ggc 768

Ile Asp Thr Gln Ser Val Met Lys Ala Leu Lys Ser Lys Arg Leu Gly

245 250 255

ggg cta gcc ctc gac gtt tac gag ggc gag cgc gcg ctc ttc tac aaa 816

Gly Leu Ala Leu Asp Val Tyr Glu Gly Glu Arg Ala Leu Phe Tyr Lys

260 265 270

gac cat tcg ggt gac atc atc cat gac gat ttg ctc atg cgc ctc acc 864

Asp His Ser Gly Asp Ile Ile His Asp Asp Leu Leu Met Arg Leu Thr

275 280 285

acg ttt cac aac gtc gtt gtg tct ggc cac cag gcg tat ttc act gaa 912

Thr Phe His Asn Val Val Val Ser Gly His Gln Ala Tyr Phe Thr Glu

290 295 300

gag gca ctc acg gaa att gcg gag tgt acg ctg agg aat ctg gat gat 960

Glu Ala Leu Thr Glu Ile Ala Glu Cys Thr Leu Arg Asn Leu Asp Asp

305 310 315 320

tgg gcg aag gga gtg cca acg gcg aat gcg ctg gtg cag ggc agg aat 1008

Trp Ala Lys Gly Val Pro Thr Ala Asn Ala Leu Val Gln Gly Arg Asn

325 330 335

tcg aat ggg agg agg gag cgg ggg ttg gcg cgg ctc tga 1047

Ser Asn Gly Arg Arg Glu Arg Gly Leu Ala Arg Leu

340 345

<210> 51

<211> 348

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 51

Met Lys Leu Thr Val Phe Ser Ala Lys Pro Tyr Asp Ile Glu Tyr Leu

1 5 10 15

Gly Gly Ile Ala Thr Asn Gln Asn Ser Ser Pro Ala Ile Glu Ile Asn

20 25 30

Phe Leu His Val Pro Leu Ser Ser Glu Thr Ala Ala Phe Ala Asn Gly

35 40 45

Ala Asp Ala Val Cys Val Phe Val His Asp Val Leu Asp Ala Asn Val

50 55 60

Leu Arg Glu Leu Tyr Ala Ala Gly Val Arg Ala Ile Leu Phe Arg Cys

65 70 75 80

Ser Gly Tyr Asn Asn Ile Asp Leu Arg Glu Ala Glu Arg Leu Gly Phe

85 90 95

Phe Val Ala Asn Val Pro Ser Tyr Ser Pro Glu Ala Val Ala Glu Phe

100 105 110

Ala Val Ala Leu Ile Gln Thr Leu Asn Arg Lys Thr His Arg Ala Tyr

115 120 125

Asn Arg Val Arg Asp Gly Asn Phe Asn Leu Asp Gly Leu Leu Gly Arg

130 135 140

Thr Leu His Gly Lys Thr Val Gly Ile Val Gly Ser Gly Arg Ile Gly

145 150 155 160

Leu Ala Met Ala Gln Ile Val Gln Gly Phe Gly Cys Lys Leu Leu Ala

165 170 175

Tyr Asp Pro Arg Pro Thr Glu Ala Phe Lys Lys Tyr Gly Glu Tyr Val

180 185 190

Asp Leu Asp Thr Leu Leu Ser Gln Cys Asp Ile Val Ser Leu His Cys

195 200 205

Pro Leu Met Asp Ser Thr Gln His Ile Ile Asn Asp Thr Thr Val Ser

210 215 220

Lys Met Lys Arg Gly Ala Met Leu Val Asn Thr Ser Arg Gly Gly Leu

225 230 235 240

Ile Asp Thr Gln Ser Val Met Lys Ala Leu Lys Ser Lys Arg Leu Gly

245 250 255

Gly Leu Ala Leu Asp Val Tyr Glu Gly Glu Arg Ala Leu Phe Tyr Lys

260 265 270

Asp His Ser Gly Asp Ile Ile His Asp Asp Leu Leu Met Arg Leu Thr

275 280 285

Thr Phe His Asn Val Val Val Ser Gly His Gln Ala Tyr Phe Thr Glu

290 295 300

Glu Ala Leu Thr Glu Ile Ala Glu Cys Thr Leu Arg Asn Leu Asp Asp

305 310 315 320

Trp Ala Lys Gly Val Pro Thr Ala Asn Ala Leu Val Gln Gly Arg Asn

325 330 335

Ser Asn Gly Arg Arg Glu Arg Gly Leu Ala Arg Leu

340 345

<210> 52

<211> 936

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(936)

<400> 52

atg acg aaa agg gaa agc aac act cta gcg gtt ctc gga tgc ggt atg 48

Met Thr Lys Arg Glu Ser Asn Thr Leu Ala Val Leu Gly Cys Gly Met

1 5 10 15

gtt ttt ctt gta tca tta tta gat ctg gct aac aga ctg tta ggt gcg 96

Val Phe Leu Val Ser Leu Leu Asp Leu Ala Asn Arg Leu Leu Gly Ala

20 25 30

ctt ggc acc gcc att ctc tca ggc ata ctt gct tct atg gca gat cag 144

Leu Gly Thr Ala Ile Leu Ser Gly Ile Leu Ala Ser Met Ala Asp Gln

35 40 45

aca gcc gat gat tcg ggt cgc ctg ttt acg aat ttc act gcc tgt gtg 192

Thr Ala Asp Asp Ser Gly Arg Leu Phe Thr Asn Phe Thr Ala Cys Val

50 55 60

cgt cgc aaa gag acc ggt gct gct gtt agt gat aag atc agt tcg cac 240

Arg Arg Lys Glu Thr Gly Ala Ala Val Ser Asp Lys Ile Ser Ser His

65 70 75 80

gcc aat gca aac aaa gtc gag ata ttg aac aag gaa aat cta cgg ggc 288

Ala Asn Ala Asn Lys Val Glu Ile Leu Asn Lys Glu Asn Leu Arg Gly

85 90 95

gtc aag caa gca gat gct gtt ctc tta gcc tgc caa acg cac cta tac 336

Val Lys Gln Ala Asp Ala Val Leu Leu Ala Cys Gln Thr His Leu Tyr

100 105 110

aaa gct ctg ttc gac gag cca ggg atg cga gag gca ctg aag aag aaa 384

Lys Ala Leu Phe Asp Glu Pro Gly Met Arg Glu Ala Leu Lys Lys Lys

115 120 125

ctg atc atc agc gtg ctg gct ggt gtt acc aca gca caa ctc gaa gca 432

Leu Ile Ile Ser Val Leu Ala Gly Val Thr Thr Ala Gln Leu Glu Ala

130 135 140

gcg ctg ggg aat ggt gag gat tac ttt gta atc cga gct atg cca aat 480

Ala Leu Gly Asn Gly Glu Asp Tyr Phe Val Ile Arg Ala Met Pro Asn

145 150 155 160

atc gca tgt ttt gta cga gat tct gca acc gtc atc gag aag cct cag 528

Ile Ala Cys Phe Val Arg Asp Ser Ala Thr Val Ile Glu Lys Pro Gln

165 170 175

cga act ttc cca gag gca ttg ctt cac gtc acc gac acc gtc ttc aaa 576

Arg Thr Phe Pro Glu Ala Leu Leu His Val Thr Asp Thr Val Phe Lys

180 185 190

gcc gtg ggc aac gtc ttt tac atc caa cca tct gcc tat gac ata tgt 624

Ala Val Gly Asn Val Phe Tyr Ile Gln Pro Ser Ala Tyr Asp Ile Cys

195 200 205

act gct ctc tgt ggt tca tca ccc gca ttt ctt gca gta ttt att gac 672

Thr Ala Leu Cys Gly Ser Ser Pro Ala Phe Leu Ala Val Phe Ile Asp

210 215 220

tct atg gtg gat ggt gcg gta gcc atg ggg cta agt cac aag gac gcg 720

Ser Met Val Asp Gly Ala Val Ala Met Gly Leu Ser His Lys Asp Ala

225 230 235 240

gtc gac atg gcg gcc tgc aca atg agg gga gct gcc agt ttg gtg cta 768

Val Asp Met Ala Ala Cys Thr Met Arg Gly Ala Ala Ser Leu Val Leu

245 250 255

gag agc ggc aat cct tgg acg ata cga cac cag gtg gcg tca cct gga 816

Glu Ser Gly Asn Pro Trp Thr Ile Arg His Gln Val Ala Ser Pro Gly

260 265 270

ggc tcg acc atg cag ggt cta ctg gca ctt gaa caa gga aat gtg aga 864

Gly Ser Thr Met Gln Gly Leu Leu Ala Leu Glu Gln Gly Asn Val Arg

275 280 285

tca acc atc tcc aac gcg ttg atg gtc gcc gcg aaa gaa gca aaa aag 912

Ser Thr Ile Ser Asn Ala Leu Met Val Ala Ala Lys Glu Ala Lys Lys

290 295 300

ctg ggg tcg aaa gaa aac gcg tag 936

Leu Gly Ser Lys Glu Asn Ala

305 310

<210> 53

<211> 311

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 53

Met Thr Lys Arg Glu Ser Asn Thr Leu Ala Val Leu Gly Cys Gly Met

1 5 10 15

Val Phe Leu Val Ser Leu Leu Asp Leu Ala Asn Arg Leu Leu Gly Ala

20 25 30

Leu Gly Thr Ala Ile Leu Ser Gly Ile Leu Ala Ser Met Ala Asp Gln

35 40 45

Thr Ala Asp Asp Ser Gly Arg Leu Phe Thr Asn Phe Thr Ala Cys Val

50 55 60

Arg Arg Lys Glu Thr Gly Ala Ala Val Ser Asp Lys Ile Ser Ser His

65 70 75 80

Ala Asn Ala Asn Lys Val Glu Ile Leu Asn Lys Glu Asn Leu Arg Gly

85 90 95

Val Lys Gln Ala Asp Ala Val Leu Leu Ala Cys Gln Thr His Leu Tyr

100 105 110

Lys Ala Leu Phe Asp Glu Pro Gly Met Arg Glu Ala Leu Lys Lys Lys

115 120 125

Leu Ile Ile Ser Val Leu Ala Gly Val Thr Thr Ala Gln Leu Glu Ala

130 135 140

Ala Leu Gly Asn Gly Glu Asp Tyr Phe Val Ile Arg Ala Met Pro Asn

145 150 155 160

Ile Ala Cys Phe Val Arg Asp Ser Ala Thr Val Ile Glu Lys Pro Gln

165 170 175

Arg Thr Phe Pro Glu Ala Leu Leu His Val Thr Asp Thr Val Phe Lys

180 185 190

Ala Val Gly Asn Val Phe Tyr Ile Gln Pro Ser Ala Tyr Asp Ile Cys

195 200 205

Thr Ala Leu Cys Gly Ser Ser Pro Ala Phe Leu Ala Val Phe Ile Asp

210 215 220

Ser Met Val Asp Gly Ala Val Ala Met Gly Leu Ser His Lys Asp Ala

225 230 235 240

Val Asp Met Ala Ala Cys Thr Met Arg Gly Ala Ala Ser Leu Val Leu

245 250 255

Glu Ser Gly Asn Pro Trp Thr Ile Arg His Gln Val Ala Ser Pro Gly

260 265 270

Gly Ser Thr Met Gln Gly Leu Leu Ala Leu Glu Gln Gly Asn Val Arg

275 280 285

Ser Thr Ile Ser Asn Ala Leu Met Val Ala Ala Lys Glu Ala Lys Lys

290 295 300

Leu Gly Ser Lys Glu Asn Ala

305 310

<210> 54

<211> 924

<212> DNA

<213> 棒状弯孢菌(Curvularia clavata)

<220>

<221> CDS

<222> (1)..(924)

<400> 54

atg gag agc gaa gac aat cca ttg agg ata caa acc ggc tcg ctc tgc 48

Met Glu Ser Glu Asp Asn Pro Leu Arg Ile Gln Thr Gly Ser Leu Cys

1 5 10 15

tca ttc caa cga ccg act ccg ctg gta ctc att cac gac tct agt ggc 96

Ser Phe Gln Arg Pro Thr Pro Leu Val Leu Ile His Asp Ser Ser Gly

20 25 30

acg acc ttt agt tat ttc cgc ctg ggc agc ttg aac cgt gat gtc tgg 144

Thr Thr Phe Ser Tyr Phe Arg Leu Gly Ser Leu Asn Arg Asp Val Trp

35 40 45

gct att cat gac cca cac ttt gat aaa agc acg ccg tgg aag ggc ggg 192

Ala Ile His Asp Pro His Phe Asp Lys Ser Thr Pro Trp Lys Gly Gly

50 55 60

ttt ggc gag att gcc gag cac tac ata aaa ttg att gaa acg gca gga 240

Phe Gly Glu Ile Ala Glu His Tyr Ile Lys Leu Ile Glu Thr Ala Gly

65 70 75 80

att cga ggt tcg atc ttg ctc gga gga tgg tcg ctc ggg ggt tat ctc 288

Ile Arg Gly Ser Ile Leu Leu Gly Gly Trp Ser Leu Gly Gly Tyr Leu

85 90 95

gcg ctc acg att gct cac aaa tta acg gct atc aca aat cct acc ttc 336

Ala Leu Thr Ile Ala His Lys Leu Thr Ala Ile Thr Asn Pro Thr Phe

100 105 110

tct gtc acc ggc atc ttg ctt gtt gac tct ccg tat cac acc cca atg 384

Ser Val Thr Gly Ile Leu Leu Val Asp Ser Pro Tyr His Thr Pro Met

115 120 125

agt aag ctg cca cct cac gcc cca gat ccc aac ttt caa cac ctt ccg 432

Ser Lys Leu Pro Pro His Ala Pro Asp Pro Asn Phe Gln His Leu Pro

130 135 140

gaa ctc gtc cgt aag tca ttc gag aat tac gat gtc ctt tta gac aga 480

Glu Leu Val Arg Lys Ser Phe Glu Asn Tyr Asp Val Leu Leu Asp Arg

145 150 155 160

tgg gaa cta cct cca tgg acc gcg cct gct ttg gaa ggc aaa act ata 528

Trp Glu Leu Pro Pro Trp Thr Ala Pro Ala Leu Glu Gly Lys Thr Ile

165 170 175

cgt tgt agc gcg ggt ggc aag acc ttc acg gta gca aac ggc agg atc 576

Arg Cys Ser Ala Gly Gly Lys Thr Phe Thr Val Ala Asn Gly Arg Ile

180 185 190

cta tac aag ccc cta ggt aag ggc tgg gaa gat gtc aaa atg caa agc 624

Leu Tyr Lys Pro Leu Gly Lys Gly Trp Glu Asp Val Lys Met Gln Ser

195 200 205

ttc gag cat ggc acc tct act ttg gaa cgc tac atc gaa tta ccc cca 672

Phe Glu His Gly Thr Ser Thr Leu Glu Arg Tyr Ile Glu Leu Pro Pro

210 215 220

gca gct ctg atc aga tgc gct cag gcc ata cca act gat aca gat tcg 720

Ala Ala Leu Ile Arg Cys Ala Gln Ala Ile Pro Thr Asp Thr Asp Ser

225 230 235 240

aaa atg ccg tgt ttc gta gat cga ttc cgt cac gag aca ctg cta ggt 768

Lys Met Pro Cys Phe Val Asp Arg Phe Arg His Glu Thr Leu Leu Gly

245 250 255

tgg gat agt aat ttc ccc agt ttc atc aag gcc gcc gtg gac acg aac 816

Trp Asp Ser Asn Phe Pro Ser Phe Ile Lys Ala Ala Val Asp Thr Asn

260 265 270

act cac cac ttc aac ata ttc gag tct cag aat ctc aaa cga tta acg 864

Thr His His Phe Asn Ile Phe Glu Ser Gln Asn Leu Lys Arg Leu Thr

275 280 285

ata caa ttg aat gaa tgt cta gaa gtt cta gat agc tgt tgc ccg atg 912

Ile Gln Leu Asn Glu Cys Leu Glu Val Leu Asp Ser Cys Cys Pro Met

290 295 300

gga tac tgc tga 924

Gly Tyr Cys

305

<210> 55

<211> 307

<212> PRT

<213> 棒状弯孢菌(Curvularia clavata)

<400> 55

Met Glu Ser Glu Asp Asn Pro Leu Arg Ile Gln Thr Gly Ser Leu Cys

1 5 10 15

Ser Phe Gln Arg Pro Thr Pro Leu Val Leu Ile His Asp Ser Ser Gly

20 25 30

Thr Thr Phe Ser Tyr Phe Arg Leu Gly Ser Leu Asn Arg Asp Val Trp

35 40 45

Ala Ile His Asp Pro His Phe Asp Lys Ser Thr Pro Trp Lys Gly Gly

50 55 60

Phe Gly Glu Ile Ala Glu His Tyr Ile Lys Leu Ile Glu Thr Ala Gly

65 70 75 80

Ile Arg Gly Ser Ile Leu Leu Gly Gly Trp Ser Leu Gly Gly Tyr Leu

85 90 95

Ala Leu Thr Ile Ala His Lys Leu Thr Ala Ile Thr Asn Pro Thr Phe

100 105 110

Ser Val Thr Gly Ile Leu Leu Val Asp Ser Pro Tyr His Thr Pro Met

115 120 125

Ser Lys Leu Pro Pro His Ala Pro Asp Pro Asn Phe Gln His Leu Pro

130 135 140

Glu Leu Val Arg Lys Ser Phe Glu Asn Tyr Asp Val Leu Leu Asp Arg

145 150 155 160

Trp Glu Leu Pro Pro Trp Thr Ala Pro Ala Leu Glu Gly Lys Thr Ile

165 170 175

Arg Cys Ser Ala Gly Gly Lys Thr Phe Thr Val Ala Asn Gly Arg Ile

180 185 190

Leu Tyr Lys Pro Leu Gly Lys Gly Trp Glu Asp Val Lys Met Gln Ser

195 200 205

Phe Glu His Gly Thr Ser Thr Leu Glu Arg Tyr Ile Glu Leu Pro Pro

210 215 220

Ala Ala Leu Ile Arg Cys Ala Gln Ala Ile Pro Thr Asp Thr Asp Ser

225 230 235 240

Lys Met Pro Cys Phe Val Asp Arg Phe Arg His Glu Thr Leu Leu Gly

245 250 255

Trp Asp Ser Asn Phe Pro Ser Phe Ile Lys Ala Ala Val Asp Thr Asn

260 265 270

Thr His His Phe Asn Ile Phe Glu Ser Gln Asn Leu Lys Arg Leu Thr

275 280 285

Ile Gln Leu Asn Glu Cys Leu Glu Val Leu Asp Ser Cys Cys Pro Met

290 295 300

Gly Tyr Cys

305

<210> 56

<211> 33

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 56

cggtacccgg ggatctagtc tgttgattac tcg 33

<210> 57

<211> 35

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 57

ctcgacaaag gtcattttga ctttgaatac cggtg 35

<210> 58

<211> 22

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 58

gcagttgccg ttggaccaga gg 22

<210> 59

<211> 37

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 59

atagtcataa caagccgcga cactgtaata ttaaagc 37

<210> 60

<211> 24

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 60

atgacctttg tcgagactgt agcc 24

<210> 61

<211> 39

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 61

tccaacggca actgcctatg atatactcat gttctcgtc 39

<210> 62

<211> 35

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 62

cgactctaga ggatcctgat ggtcagatgg atctg 35

<210> 63

<211> 28

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 63

gcttgttatg actatgtata catatgcg 28

<210> 64

<211> 21

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 64

gacagactct tcgtcgacgt c 21

<210> 65

<211> 22

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 65

gttgtggttg gtgttcctga gg 22

<210> 66

<211> 22

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 66

cactcgatct accaaatcga cg 22

<210> 67

<211> 21

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 67

cctatccgga tatgcagtca c 21

<210> 68

<211> 38

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 68

cggtacccgg ggatcctctg aagcggtcaa ggataacg 38

<210> 69

<211> 37

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 69

atgaagcaga gcggcgagcc taagatatgc caggagg 37

<210> 70

<211> 37

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 70

ctagcaaccg tcatgccata gacgtggcac tcgaacg 37

<210> 71

<211> 38

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 71

cgactctaga ggatccgtct taaggatggt tcagctgc 38

<210> 72

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 72

catgacggtt gctagggtcg 20

<210> 73

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 73

gccgctctgc ttcattgctg 20

<210> 74

<211> 33

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 74

cggtacccgg ggatcgaccc attgcagctt gtg 33

<210> 75

<211> 37

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 75

atgaagcaga gcggcgtgca gtatggtgtc taaaacg 37

<210> 76

<211> 36

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 76

ctagcaaccg tcatggatga atgagcaccc tgttag 36

<210> 77

<211> 39

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 77

cgactctaga ggatcgtaca ttacaaaaac ctgttgcag 39

<210> 78

<211> 35

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 78

cggtacccgg ggatcgtccc acgtgcagct tcaac 35

<210> 79

<211> 35

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 79

atgaagcaga gcggccgtgg agtatcccag gatgg 35

<210> 80

<211> 35

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 80

ctagcaaccg tcatgccagc caaagggtat catgg 35

<210> 81

<211> 33

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 81

cgactctaga ggatctgagg gcagcgtagc ctg 33

<210> 82

<211> 37

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 82

cggtacccgg ggatcgtgga taaattcgta ccctttg 37

<210> 83

<211> 36

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 83

atgaagcaga gcggcctgat ctttgttgtg gtcgtg 36

<210> 84

<211> 35

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 84

ctagcaaccg tcatgcagtt tggcacttga gcatc 35

<210> 85

<211> 36

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 85

cgactctaga ggatccacgg aaaggaactc ctacag 36

<210> 86

<211> 34

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 86

cggtacccgg ggatcctctg ggaaaagcgg ttag 34

<210> 87

<211> 34

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 87

atgaagcaga gcggcgaaga accgagagcg agag 34

<210> 88

<211> 40

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 88

ctagcaaccg tcatgcttgc atctacctag atatttcacg 40

<210> 89

<211> 36

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 89

cgactctaga ggatccagag aatcagcaga gacacc 36

<210> 90

<211> 39

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 90

cggtacccgg ggatcccctg gtagttcagt ggaagtaag 39

<210> 91

<211> 34

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 91

atgaagcaga gcggctgata gaggtacggg ggtg 34

<210> 92

<211> 34

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 92

ctagcaaccg tcatgtgctt ggctgcttca aatc 34

<210> 93

<211> 39

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 93

cgactctaga ggatcctaat acttgtcgtc ccactgatg 39

<210> 94

<211> 34

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 94

cggtacccgg ggatcgcagt acatcgtcag ggtc 34

<210> 95

<211> 36

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 95

atgaagcaga gcggcgatga ataaggcgaa ggaaag 36

<210> 96

<211> 37

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 96

ctagcaaccg tcatgccctc ttttttcttg ctgtctc 37

<210> 97

<211> 35

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 97

cgactctaga ggatcgaagg aaggacggat actgg 35

<210> 98

<211> 39

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 98

cggtacccgg ggatcgatga gcgtagaatt cgtaaaaag 39

<210> 99

<211> 32

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 99

atgaagcaga gcggcgcgaa cgggcgtttt tc 32

<210> 100

<211> 35

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 100

ctagcaaccg tcatggaagg aaggacggat actgg 35

<210> 101

<211> 37

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 101

cgactctaga ggatcccctc ttttttcttg ctgtctc 37

<210> 102

<211> 40

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 102

cggtacccgg ggatcctcct tattttgcaa cttctgatac 40

<210> 103

<211> 37

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 103

atgaagcaga gcggccgtgt tgattttggt aattttg 37

<210> 104

<211> 39

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 104

ctagcaaccg tcatggatga gcgtagaatt cgtaaaaag 39

<210> 105

<211> 32

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 105

cgactctaga ggatcgcgaa cgggcgtttt tc 32

<210> 106

<211> 37

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 106

cggtacccgg ggatccgtgt tgattttggt aattttg 37

<210> 107

<211> 40

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 107

atgaagcaga gcggcctcct tattttgcaa cttctgatac 40

<210> 108

<211> 39

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 108

ctagcaaccg tcatgctagc agccataaga gacgtaacc 39

<210> 109

<211> 34

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 109

cgactctaga ggatcgtttt cattgcatgc tccg 34

<210> 110

<211> 59

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 110

tcgacaagct tgcggccgcc acgtgactag tatggccagc gacatcaata ctcatccag 59

<210> 111

<211> 47

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 111

actagtcacg tggcggccgc ggcgcgccaa gatcgtcttg ctgtacg 47

<210> 112

<211> 41

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 112

gatgcgctag cggccgcgaa gtggtccttg tcgctggtga c 41

<210> 113

<211> 28

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 113

tgccgttcgc attcataggc atctcgtc 28

<210> 114

<211> 25

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 114

tgaatgcgaa cggcaaggtt gacag 25

<210> 115

<211> 25

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 115

cttggttgct ggcttcgtcg ttgtc 25

<210> 116

<211> 25

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 116

aagccagcaa ccaagtcgaa gattg 25

<210> 117

<211> 43

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 117

gtcactagtg cggccgccta tttttgcaag atcttgttca aac 43

<210> 118

<211> 29

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 118

ggactagtat gactgaaccc acatggaag 29

<210> 119

<211> 29

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 119

ggactagttt aataatctac ttcaagcac 29

<210> 120

<211> 33

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 120

ataagaatgc ggccgcatgg cgttgcaaga gcg 33

<210> 121

<211> 36

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 121

ataagaatgc ggccgctcaa gatgggaaag ccgctg 36

<210> 122

<211> 28

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 122

ctagctagca tgagtgctat cgagctgc 28

<210> 123

<211> 28

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 123

ctagctagct cagcgattga gggcctgg 28

<210> 124

<211> 36

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 124

ataagaatgc ggccgcatga agctcaccgt tttcag 36

<210> 125

<211> 32

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 125

ataagaatgc ggccgctcag agccgcgcca ac 32

<210> 126

<211> 29

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 126

ggactagtat gacgaaaagg gaaagcaac 29

<210> 127

<211> 27

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 127

ggactagtct acgcgttttc tttcgac 27

<210> 128

<211> 29

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 128

ctagctagca tggagagcga agacaatcc 29

<210> 129

<211> 27

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 129

ctagctagct cagcagtatc ccatcgg 27

<210> 130

<211> 36

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 130

atttgcggcc gcatggaccc gagacagtca cggatc 36

<210> 131

<211> 36

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 131

atttgcggcc gcttatggtg tggtgggttg ccattc 36

<210> 132

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 132

gacgccacga acgcatagac 20

<210> 133

<211> 21

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 133

ttcccagaga ggtagatcga c 21

<210> 134

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 134

gaccgttaca gcgagttcag 20

<210> 135

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 135

ctgaattcct cgcacagaac 20

<210> 136

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 136

gaagttgaga acgccatgct 20

<210> 137

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 137

gatgcgagat gggagcatgt 20

<210> 138

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 138

gccctactag atctgaccac 20

<210> 139

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 139

gctgttacct tttcctcctc 20

<210> 140

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 140

agatcttaga cgagctgctc 20

<210> 141

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 141

aaacagtcgc gaagcgactg 20

<210> 142

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 142

acgtccagga agctatcgag 20

<210> 143

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 143

attgagggcc tgggcttgac 20

<210> 144

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 144

gtgatgaagg cgctgaagag 20

<210> 145

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 145

ctccgcaatt tccgtgagtg 20

<210> 146

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 146

tgactctatg gtggatggtg 20

<210> 147

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 147

ccttgttcaa gtgccagtag 20

<210> 148

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 148

gattccgtca cgagacactg 20

<210> 149

<211> 20

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 149

agtatcccat cgggcaacag 20

<210> 150

<211> 18

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 150

acgttcaaga ccttccag 18

<210> 151

<211> 18

<212> DNA

<213> 人工的(Artificial)

<220>

<223> 合成的DNA

<400> 151

gttccggatg atttgcag 18

PCT/RO/134表

Claims

1.一种环状肽化合物合成相关基因，其编码如下蛋白质，所述蛋白质从N末端侧起依次具有以下各模块：

第一模块，其从N末端侧起依次具有：由SEQ ID NO:1所示的氨基酸序列或由与SEQ IDNO:1所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第一腺苷酰化结构域、由SEQ ID NO:2所示的氨基酸序列或由与SEQ ID NO:2所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第一肽基载体蛋白结构域；

第二模块，其从N末端侧起依次具有：由SEQ ID NO:3所示的氨基酸序列或由与SEQ IDNO:3所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第一缩合结构域、由SEQID NO:4所示的氨基酸序列或由与SEQ ID NO:4所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第二腺苷酰化结构域、由SEQ ID NO:5所示的氨基酸序列或由与SEQ IDNO:5所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第二肽基载体蛋白结构域；

第三模块，其从N末端侧起依次具有：由SEQ ID NO:6所示的氨基酸序列或由与SEQ IDNO:6所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第二缩合结构域、由SEQID NO:7所示的氨基酸序列或由与SEQ ID NO:7所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第三腺苷酰化结构域、由SEQ ID NO:8所示的氨基酸序列或由与SEQ IDNO:8所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第一N-甲基转移酶结构域、由SEQ ID NO:9所示的氨基酸序列或由与SEQ ID NO:9所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第三肽基载体蛋白结构域；

第四模块，其从N末端侧起依次具有：由SEQ ID NO:10所示的氨基酸序列或由与SEQ IDNO:10所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第三缩合结构域、由SEQID NO:11所示的氨基酸序列或由与SEQ ID NO:11所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第四腺苷酰化结构域、由SEQ ID NO:12所示的氨基酸序列或由与SEQID NO:12所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第四肽基载体蛋白结构域；

第五模块，其从N末端侧起依次具有：由SEQ ID NO:13所示的氨基酸序列或由与SEQ IDNO:13所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第四缩合结构域、由SEQID NO:14所示的氨基酸序列或由与SEQ ID NO:14所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第五腺苷酰化结构域、由SEQ ID NO:15所示的氨基酸序列或由与SEQID NO:15所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第二N-甲基转移酶结构域、由SEQ ID NO:16所示的氨基酸序列或由与SEQ ID NO:16所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第五肽基载体蛋白结构域；

第六模块，其从N末端侧起依次具有：由SEQ ID NO:17所示的氨基酸序列或由与SEQ IDNO:17所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第五缩合结构域、由SEQID NO:18所示的氨基酸序列或由与SEQ ID NO:18所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第六腺苷酰化结构域、由SEQ ID NO:19所示的氨基酸序列或由与SEQID NO:19所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第三N-甲基转移酶结构域、由SEQ ID NO:20所示的氨基酸序列或由与SEQ ID NO:20所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第六肽基载体蛋白结构域；

第七模块，其从N末端侧起依次具有：由SEQ ID NO:21所示的氨基酸序列或由与SEQ IDNO:21所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第六缩合结构域、由SEQID NO:22所示的氨基酸序列或由与SEQ ID NO:22所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第七腺苷酰化结构域、由SEQ ID NO:23所示的氨基酸序列或由与SEQID NO:23所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第四N-甲基转移酶结构域、由SEQ ID NO:24所示的氨基酸序列或由与SEQ ID NO:24所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第七肽基载体蛋白结构域；

第八模块，其从N末端侧起依次具有：由SEQ ID NO:25所示的氨基酸序列或由与SEQ IDNO:25所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第七缩合结构域、由SEQID NO:26所示的氨基酸序列或由与SEQ ID NO:26所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第八腺苷酰化结构域、由SEQ ID NO:27所示的氨基酸序列或由与SEQID NO:27所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第八肽基载体蛋白结构域；

第九模块，其从N末端侧起依次具有：由SEQ ID NO:28所示的氨基酸序列或由与SEQ IDNO:28所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第八缩合结构域、由SEQID NO:29所示的氨基酸序列或由与SEQ ID NO:29所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第九腺苷酰化结构域、由SEQ ID NO:30所示的氨基酸序列或由与SEQID NO:30所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第五N-甲基转移酶结构域、由SEQ ID NO:31所示的氨基酸序列或由与SEQ ID NO:31所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第九肽基载体蛋白结构域；

第十模块，其从N末端侧起依次具有：由SEQ ID NO:32所示的氨基酸序列或由与SEQ IDNO:32所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第九缩合结构域、由SEQID NO:33所示的氨基酸序列或由与SEQ ID NO:33所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第十腺苷酰化结构域、由SEQ ID NO:34所示的氨基酸序列或由与SEQID NO:34所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第十肽基载体蛋白结构域、由SEQ ID NO:35所示的氨基酸序列或由与SEQ ID NO:35所示的氨基酸序列具有70％以上同一性的氨基酸序列组成的第十缩合结构域，

2.根据权利要求1所述的环状肽化合物合成相关基因，其特征在于，所述蛋白质为以下(a)～(c)中任一项的蛋白质：

(a)由SEQ ID NO:37所示的氨基酸序列组成的蛋白质；

(b)由与SEQ ID NO:37所示的氨基酸序列具有70％以上同一性的氨基酸序列组成，且具有由弯孢属丝状真菌产生的环状肽化合物的非核糖体肽合成活性的蛋白质；

(c)由与SEQ ID NO:36所示的碱基序列的互补链在严格条件下杂交的多聚核苷酸所编码，且具有由弯孢属丝状真菌产生的环状肽化合物的非核糖体肽合成活性的蛋白质。

3.根据权利要求1所述的环状肽化合物合成相关基因，其特征在于，所述环状肽化合物合成相关基因来源于弯孢属丝状真菌。

4.根据权利要求3所述的环状肽化合物合成相关基因，其特征在于，所述丝状真菌为棒状弯孢菌(Curvularia clavata)。

5.一种环状肽化合物合成相关基因，其编码以下(a)～(c)中任一项的蛋白质：

(a)由SEQ ID NO:39所示的氨基酸序列组成的蛋白质；

6.根据权利要求5所述的环状肽化合物合成相关基因，其特征在于，所述环状肽化合物合成相关基因来源于弯孢属丝状真菌。

7.根据权利要求6所述的环状肽化合物合成相关基因，其特征在于，所述丝状真菌为棒状弯孢菌。

8.一种由弯孢属丝状真菌产生的环状肽化合物的制造方法，所述制造方法包括以下步骤：

培养转化体，所述转化体导入有权利要求1～4中任一项所述的环状肽化合物合成相关基因和参与弯孢属丝状真菌产生环状肽化合物的一组基因；以及

从培养的转化体和/或培养液中回收所述环状肽化合物。

9.根据权利要求8所述的环状肽化合物的制造方法，其特征在于，所述一组基因含有以下[1]～[7]的基因：

10.根据权利要求8所述的环状肽化合物的制造方法，其特征在于，所述转化体以米曲霉(Aspergillus oryzae)为宿主。

11.一种转化体，其导入有权利要求1～4中任一项所述的环状肽化合物合成相关基因和参与弯孢属丝状真菌产生环状肽化合物的一组基因。

12.根据权利要求11所述的转化体，其特征在于，所述一组基因含有以下[1]～[7]的基因：

13.根据权利要求11所述的转化体，其特征在于，所述转化体以米曲霉为宿主。

14.一种弯孢属丝状真菌，其具有权利要求1～4中任一项所述的环状肽化合物合成相关基因。

15.根据权利要求14所述的弯孢属丝状真菌，其特征在于，所述弯孢属丝状真菌为棒状弯孢菌。

16.根据权利要求14所述的弯孢属丝状真菌，其特征在于，所述弯孢属丝状真菌的保藏编号为NITE BP-02399。