CN1249233C - 肺炎衣原体表面蛋白 - Google Patents
肺炎衣原体表面蛋白 Download PDFInfo
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Abstract
本发明涉及对来自人呼吸道病原体肺炎衣原体的、编码大小约为89-101kDa和56-57kDa(较佳的约为89.6-100.3kDa和约为56.1kDa)的表面膜蛋白的基因家族成员的鉴定。本发明涉及新的DNA序列,对应蛋白质的推定的氨基酸序列,以及该DNA序列和蛋白在病理学和流行病学上诊断由肺炎衣原体引起的感染的用途,以及作为疫苗组分的用途。
Description
本发明涉及人呼吸道病原体肺炎衣原体(Chlamydia pneumoniae)的、编码大小约为89-101kDa和56-57kDa(较佳的约为89.6-100.3kDa和约为56.1kDa)的表面(surfaceexposed)膜蛋白的基因家族成员的鉴定。本发明涉及新的DNA序列,其对应蛋白质的推定的氨基酸序列,以及该DNA序列和蛋白在病理学和流行病学上诊断由肺炎衣原体引起的感染和作为疫苗组分的用途。
总体背景
肺炎衣原体是专性胞内细菌(Christiansen和Birkelund(1992);Grayston等人,(1986))。它具有和革兰阴性菌一样的细胞壁结构,具有外膜、周质间隙和胞质膜。用洗涤剂十二烷基肌氨酸钠可以纯化革兰阴性菌的外膜。该组分被命名为“外膜复合物(OMC)”(Caldwell等人,(1981))。肺炎衣原体的COMC(衣原体外膜复合物)含有四组蛋白质:经SDS-PAGE测得的98kDa高分子量蛋白、62/60kDa的富含半胱氨酸的外膜蛋白2(Omp2)的两条条带、38kDa的主要外膜蛋白(MOMP)、以及12kDa的低分子量脂蛋白Omp3。Omp2/Omp3和MOMP蛋白存在于所有衣原体种类的COMC中,已经从沙眼衣原体(C.trachomtis)、鹦鹉热衣原体(C.psittaci)和肺炎衣原体中克隆出这些基因。然而编码肺炎衣原体COMC中98kDa蛋白的基因还未被鉴别或克隆。
肺炎衣原体血清学和鉴定的现有状况
肺炎衣原体是一种专性胞内细菌,属于衣原体属,该衣原体属可以分为四种:沙眼衣原体、肺炎衣原体、鹦鹉热衣原体和C.pecorum。四个种类的共同之处是它们在细胞内的专性生长,且它们具有胞外感染性颗粒(原体,EB)和胞内复制形式(网状体,RB)的双相生命周期。另外,衣原体种类的特征是在人类感染中高度免疫原性的共同脂多糖(LPS)表位。沙眼衣原体引起人眼感染(沙眼)和生殖感染。鹦鹉热衣原体是一类可变的动物病原体,其中的禽株偶尔会感染人并引起严重的肺炎鸟疫。第一个肺炎衣原体分离物从眼感染获得,但是它被归类为非典型(non-typable)的衣原体。在芬兰肺炎流行性爆发时,发现患者在衣原体属特异性测试(淋巴肉芽肿皮肤试验抗原测试)中有阳性反应,且患者表现非典型的衣原体分离物的滴度升高。在西雅图上呼吸道感染爆发时获得了类似的分离物,该衣原体分离物归类为一种新的种类肺炎衣原体(Grayston等人,1989)。另外,有人指出肺炎衣原体涉及到粥样动脉硬化病变发展和刺激性支气管哮喘(Kuo等人,1995)。这两种病症被认为是由于慢性感染或过敏反应或两者共同引起的。
肺炎衣原体感染的诊断
诊断肺炎衣原体引起的急性呼吸道感染是困难的。对患者样品的肺炎衣原体培养是不敏感的,甚至是选择合适的组织培养细胞未分离时也如此。因此Campbell等人(1992)开发出一种肺炎衣原体特异性的聚合酶链反应(PCR)。
尽管在一些研究中已经用该PCR方法检测了肺炎衣原体,但是该方法是否适用于所有的临床场合仍有争论。其原因是,急性呼吸道感染中携带肺炎衣原体的细胞还未确定,且预计会有慢性携带状态,只是不知道它们存在于哪些器官和细胞中。另外,PCR测试很难进行,因为这些细菌的产量很低,且患者样品中存在抑制性的物质。因此,开发出敏感的、特异性的血清型诊断方法来检测急性和慢性感染是将会有很大价值。衣原体感染的血清学诊断方法目前是基于属特异性的测试(如淋巴肉芽肿皮肤试验抗原测试和ELISA(测定LPS的抗体)),或是更特异性的种属测试(用微量免疫荧光法(Micro-IF)测定针对纯化的EB的抗体)(Wang等人,1970)。然而,微量免疫荧光法要用显微镜来读数,且为了确保有正确的读数,必须将结果与用作抗原(由于与共有的LPS表位的交叉反应抗体)的沙眼衣原体的结果比较。因此,正如Kuo等人(1995)年所表述的,“本领域中主要需要一种用于临床实验室的测试感染的迅速、可靠实验室方法”,本领域迫切需要开发出用于针对肺炎衣原体的种特异性诊断方法。另外,肺炎衣原体可能涉及粥样动脉硬化和支气管哮喘显然也使得开发有效的疫苗有正当的理由。
发明详细公开
本发明的目的是提供有效诊断肺炎衣原体感染的方法以及开发出有效抵抗该微生物感染的疫苗。因此,本发明涉及种特异性的哺乳动物(如人)体内肺炎衣原体感染的诊断测试方法,所述测试是根据对抗体进行检测,该抗体针对大小约为89-101kDa和56-57kDa(较佳的约为89.6-100.3kDa和56.1kDa)(推导的氨基酸序列的大小范围为100.3至89.6,除大小为56.1的Omp13外)的表面膜蛋白,或是基于对编码该蛋白或其变体或亚序列的核酸片段进行检测。本发明还涉及本发明蛋白的氨基酸序列,其变体和亚序列,以及编码这些蛋白或其变体或亚序列的核酸片段。本发明还涉及针对本发明蛋白的抗体。本发明还涉及本发明的核酸片段和蛋白在诊断肺炎衣原体以及抗肺炎衣原体疫苗中的用途。
在本发明公开前,只有很少的肺炎衣原体基因被测序。它们主要是编码已知的沙眼衣原体同系物(MOMP、Omp2、Omp3、Kdo转移酶)的基因、热休克蛋白基因GroE1/Es和Dnak(一种核酸酶P同系物)和编码功能未知的76kDa蛋白的基因。为何至今只有如此少的基因被克隆的原因是因为从宿主细胞纯化后能获得的肺炎衣原体的产量非常低。在这种纯化后,DNA必须从EB中纯化出,而在此步骤肺炎衣原体DNA容易被宿主细胞DNA污染。除了这些固有的困难外,培育肺炎衣原体并用DNA技术产生很少数量(几个μ)DNA的表达文库非常困难。自1993年起已经知道(Melgosa等人,1993),98kDa的蛋白存在于肺炎衣原体的OMC中。尽管Melgosa提到98kDa的蛋白条带是肺炎衣原体OMC的一部分,但是其基因序列以及推导的氨基酸序列一直未被确定。该文中只描述了用SDS-PAGE大致分离出的肺炎衣原体蛋白的条带。然而,在本发明前,编码该蛋白的基因一直未被确定。发现98kDa蛋白与人血清只有很弱的反应或没有反应(Campbell等人,1990),在本发明者的工作之前,还没有认识到89-101kDa蛋白是表面外露的或它们实际上有免疫原性(见下文)。在该报道中描述了许多人血清样品能与SDS-PAGE中迁移至98kDa的肺炎衣原体蛋白反应。该蛋白没有进一步作特性分析,因此它与本申请没有冲突。
Campbell等人在1990年描述了从中分离出肺炎衣原体的四位患者的血清在采用全细胞裂解物的免疫印迹中与98kDa的条带反应。他们还证实,这些血清样品在沙眼衣原体或鹦鹉热衣原体中没有识别出具有相似分子量的蛋白,因此,他们建议存在于98kDa条带中的蛋白可用作潜在的诊断工具来识别肺炎衣原体感染。但没有对98kDa区域中的蛋白成分作进一步的特性分析,也没有显示出其在衣原体中的位置。
Halme等人1997年描述了92-98kDa肺炎衣原体蛋白中存在人T细胞表位。从总衣原体蛋白的SDS-PAGE中洗脱出该蛋白,但是该蛋白的身份没有被确定。
用抗体来筛选表达文库是克隆编码蛋白的抗原性部分基因片段众所周知的方法。然而,由于患者的血清没有表现出与98kDa蛋白有明显的反应,因此不可能用患者血清来克隆该蛋白。
已知由发明者获得的单克隆抗体能与肺炎衣原体表面上的构象表位反应,它们还与肺炎衣原体OMC反应(经免疫电子显微镜测得)(Christiansen等人,1994)。另外,98kDa蛋白是肺炎衣原体OMC中唯一未知的蛋白(Melgosa等人,1993)。本发明者选择采用非常规的步骤来克隆编码至今未知的98kDa蛋白的基因:纯化肺炎衣原体OMC,在免疫接种前用SDS处理抗原破坏免疫原性构象表位。从而获得对免疫原性较低的线性表位的抗体(PAB150)。这提供了获得能检测该蛋白的抗血清的可能性,并表明编码本发明的89-101kDa和56kDa蛋白的基因家族能在重组体大肠杆菌的菌落印迹中检测到。
肺炎衣原体感染的小鼠产生了针对发明者鉴定并命名为Omp4-15的抗体,但是不识别通常用于SDS-PAGE和免疫印迹的经SDS处理热变性的抗原。但是,如果抗原没有热变性,则可见到强反应。因此,如果在人感染中见到类似的反应,则本发明的抗原很有可能在血清诊断测试中具有不可估量的用途,并且很可能用作预防感染的疫苗。
通过产生针对肺炎衣原体COMC的抗体,获得与所有蛋白反应的多克隆抗体(PAB150)。用该抗体鉴别肺炎衣原体DNA表达文库中编码89.6-101.3kDa和56.1kDa的基因。与本发明有关的一个问题是在肺炎衣原体中发现了包含许多类似基因的一个家族。因此,需要大量不同的克隆来鉴别诸片段簇。本发明者成功克隆并测序以上四个基因只是因为用SDS-变性抗原产生的家兔抗体含有针对位于该蛋白家族不同成员中的许多不同表位的抗体。通过该方法,一个基因已被完全测序,第二个基因除远部外已测序,并获得了两个附加基因的更短的片段。为了获得附加基因的DNA序列并搜寻该基因家族的更多成员,用测序基因衍生的引物和数据库中已经公开基因的引物进行长范围(long range)PCR。该方法检测到属于该家族的另外8个基因。这些基因位于两个基因簇中:Omp12,11,10,5,4,13和14在一个簇中,Omp6,7,8,9和15在第二个簇中。从Omp4,5,6,7,8,9,10,11和13获得全序列,并获得Omp12,14部分序列。Omp13是1545核苷酸的截短的基因,全长基因的其余部分为2526(Omp7)至2838(Omp15)的核苷酸。推导的氨基酸序列揭示,推定的多肽为89.6至100.3kDa,除Omp13为56.1kDa外。与所有序列相比,推导的氨基酸序列的排列表现出最大相同性为49%(Omp5/Omp9)。除了Omp13外,最低的同源性是Omp7与其它任何氨基酸序列的相同性不到34%。Omp13与所有其它序列的同源性评分为29-32%。
在本文中,SEQ ID NO:1和2对应于Omp4,SEQ ID NO:3和4对应于Omp5,SEQ ID NO:5和6对应于Omp6,SEQ ID NO:7和8对应于Omp7,SEQ ID NO:9和10对应于Omp8,SEQ ID NO:11和12对应于Omp9,SEQ ID NO:13和14对应于Omp10,SEQ ID NO:15和16对应于Omp11,SEQ ID NO:17和18对应于Omp12,SEQ ID NO:19和20对应于Omp13,SEQ ID NO:21和22对应于Omp14,SEQ ID NO:23和24对应于Omp15。
下面列出了本发明的Omp蛋白估计的大小。Omp4的大小为98.9kDa,Omp5的估计大小为97.2kDa,Omp6的估计大小为100.3kDa,Omp7的估计大小为89.7kDa,Omp8的估计大小为90.0kDa,Omp9的估计大小为96.7kDa,Omp10的估计大小为98.4kDa,Omp11的估计大小为97.6kDa,Omp13的估计大小为56.1kDa,Omp12和Omp14为一部分。
另外,SEQ ID NO:25是SEQ ID NO:3的亚序列,SEQ ID NO:26是SEQ ID NO:4的亚序列,SEQ ID NO:27是SEQ ID NO:5的亚序列,SEQ ID NO:28是SEQ ID NO:6的亚序列,SEQ ID NO:29是SEQ ID NO:7的亚序列,SEQ ID NO:30是SEQ ID NO:8的亚序列。
部分omp蛋白以融合蛋白形式表达并产生了针对这些蛋白的小鼠多克隆单特异性抗体。这些抗体在免疫荧光和免疫电镜法中与肺炎衣原体的表面反应。这第一次表明肺炎衣原体中89-101kDa和56-57kDa蛋白家族包含表面的外膜蛋白。这一重要发现导致这样一个认识,即89-101kDa和56-57kDa肺炎衣原体蛋白家族成员是开发血清学诊断测试肺炎衣原体、以及开发抵抗肺炎衣原体感染的疫苗(根据采用这些蛋白)的优秀的候选物。另外,这些蛋白可用作流行病学标记,针对这些蛋白的多克隆单特异性血清可用来检测人组织中的肺炎衣原体或用来检测组织培养物中的肺炎衣原体分离物。另外,编码89-101kDa和56-57kDa(如89.6-100.3kDa和56.1蛋白家族)的基因可用来开发基于核酸检测/扩增的种特异性诊断测试。
将全长Omp14克隆到允许Omp4多肽表达的表达载体系统中。用该多肽作为抗原来免疫家兔。由于该蛋白在变性条件下纯化,因此其抗体不与肺炎衣原体天然表面反应,但是在采用纯化的肺炎衣原体EB作为抗原的免疫印迹中,它和98kDa蛋白反应。另外,抗体在试验性感染小鼠的石蜡包埋肺组织切片中反应。
本发明较宽的方面涉及种特异性地诊断测试肺炎衣原体感染哺乳动物(如人)的方法,所述测试方法包括检测患者体内或较佳的是患者样品中是否存在针对分子量为89-101kDa或56-57kDa的肺炎衣原体外膜蛋白的抗体,或检测是否存在编码所述外膜蛋白或其片段的核酸片段。
在本申请的内容中,术语“患者样品”应指患者(如人患者)的一定量的血清、血浆、粘液、组织、咳出物、强迫咳出的痰液或支气管吸出物、尿液、脑脊髓液、粥样动脉硬化病灶、粘膜拭子(mucosal swap)、来自所述患者的组织培养的细胞、或以任何方式源自所述患者的物质。本发明的人体内测试包括本领域中已知的皮肤测试,如真皮内测试,例如类似于Mantaux测试。在对于测试非常敏感的某些患者(通常情况是儿童)体内,测试可以是非侵入型的,例如用膏药在皮肤表面测试。
在本文中,术语89-101kDa蛋白指通常在肺炎衣原体外膜中的蛋白,其在SDS-PAGE中所见的一条或多条条带,表观分子量基本上在89-101kDa范围内。根据推导的氨基酸序列,分子大小在89.6-100.3kDa之间不等。
基于利用属于本申请书公开的基因家族的基因的种特异性血清诊断测试在本发明的范围内。
本发明的较佳实例涉及本发明的种特异性诊断测试,其中外膜蛋白具有选自SEQID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22和SEQ ID NO:24的序列。
当采用本发明的蛋白时,术语“变体”应理解成表现出与本发明的某一种蛋白的相似性低于100%的氨基酸序列。变体序列的大小可以和与之比较的序列相同或不同。变体通常宜表现出序列相似性至少为50%,较佳的至少60%,更佳的至少70%,例如至少80%、90%、95%或98%。
关于本发明蛋白序列的术语“序列相似性”指本发明蛋白和长度相同或不同的对比蛋白中相同的和保守性变化的氨基酸残基(在位置和类型上)的百分数。关于本发明蛋白序列的术语“序列相同性”指本发明蛋白和长度相同或不同的对比蛋白中在位置和类型上相同的氨基酸的百分数。
在本发明的范围内,本发明的一种蛋白的亚序列是指取自SEQ ID NO:2、SEQ IDNO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22或SEQ ID NO:24的氨基酸残基的连续序列。一个亚序列通常包含至少100个氨基酸,较佳的至少80个氨基酸,更佳的至少70个氨基酸,如50个氨基酸。它甚至可以短达10-50个氨基酸,例如20-40个氨基酸,例如约30个氨基酸。亚序列通常表现出的序列同源性至少为50%,较佳的至少为60%,更佳的至少70%,例如至少80%,如至少90%,95%或98%。
本发明的诊断测试所包括的免疫试验选自直接或间接的EIA(如ELISA)、免疫印迹技术(如Western印迹)、放射免疫试验和其它任何非酶联抗体结合试验或诸如荧光、凝集或沉淀反应的程序,以及比浊法。
本发明的一个较佳实例涉及本发明的种特异性诊断测试,所述测试包括ELISA,其中检测样品中针对本发明蛋白或其片段的抗体。
本发明的一个较佳的实例是以检测样品中针对本发明蛋白的抗体为基础的ELISA。该ELISA可采用本发明的蛋白或其变体(即抗原)作为包被试剂。ELISA通常根据本领域熟知的标准方法(例如David Lane Harlow编辑的“抗体实验手册”(ColdSpring Habor laboratories,1988)中所述的方法,该文纳入本文作参考)来进行。
重组蛋白可用按照下文实施例中所述的方法获得的DNA序列来生产。这些DNA序列(包括本发明基因家族中每个基因的整个编码区)将被克隆到表达载体中,从该表达载体中可以纯化获得推导的蛋白序列。在ELISA中用单克隆和多克隆抗体以及实验性感染的小鼠的血清和人患者的血清分析纯化获得的蛋白的反应性。
从实验性感染的小鼠血清的反应性知道,它主要识别的是非线性表位。因此,可以考虑用本领域中已知的不同形式的纯化方案来分析不连续表位的存在,和分析人免疫应答是否也针对这类表位。
本发明的较佳实例涉及本发明的种特异性诊断测试,其中核酸片段具有选自SEQID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:21和SEQ ID NO:23的序列。
关于本发明的核酸片段,术语“变体”应理解成表现出的序列同源性低于100%的核酸序列。变体序列的大小可以和与之比较的序列相同或不同。变体通常宜表现出序列同源性至少为50%,较佳的至少60%,更佳的至少70%,例如至少80%、90%、95%或98%。
关于本发明的核酸片段,术语“序列同源性”指本发明的核酸片段中的核酸在位置和类型上与长度相同或不同的序列对比时相匹配核酸百分数。
为了获得关于本发明每个基因总体分布的信息,对于所有可获得的肺炎衣原体分离物上的每个基因进行PCR。这将提供关于本发明的基因或核酸片段的总体变化性的信息。对可变区测序。可用PCR从患者样品扩增出流行病学基因的可变部分。不变的部分可用来PCR扩增和分析用于诊断测试的可能性。预计,如果发现可变性,则可变区的PCR可用于流行病学。不变区的PCR可用作种特异性诊断测试。用编码所有已知分离物中不变蛋白的基因作为PCR的靶来制备编码功能未知蛋白的基因。
本发明的特别佳的实例涉及本发明的诊断测试,其中利用核酸扩增、较佳的是聚合酶链反应(PCR)来检测核酸片段。
以PCR为基础的测试在本发明的范围内,该测试的目的是检测本发明的核酸片段或其变体。PCR测试通常根据本领域熟知的方法来进行,其通常包括能检测和区别本发明的核酸片段的PCR测试。较佳的是定量的竞争性PCR测试或嵌套式PCR测试。本发明的PCR测试通常根据EP B 540 588、EP A 586 112、EP A 643 140或EPA 669 401中详细描述的方法来设计,这些专利均纳入本文作参考。
在本发明的范围内,本发明的一种核酸片段的变体和亚序列指取自SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:21和SEQ ID NO:23的连续延伸核酸。变体或亚序列宜包含至少100个核酸,较佳的至少80个核酸,更佳的至少70个核酸,例如至少50个核酸。它甚至可以短达10-50个核酸,例如20-40个核酸,例如约30个核酸。亚序列通常表现出至少30%的序列同源性,较佳的为至少60%,更佳的为至少70%,例如至少80%,如至少90%、95%或98%。亚序列越短,所需的同源性越高。因此,100个核酸或更少的亚序列必须表现出至少80%的同源性。
本发明的一个非常重要的方面涉及本发明衍生自肺炎衣原体的蛋白,该蛋白具有的氨基酸序列选自SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22和SEQ ID NO:24,具有的序列相似性至少为50%,较佳的至少60%,更佳的至少70%,例如至少80%,如至少90%、95%或98%,并具有类似的生物功能。
术语“类似的生物功能”指该蛋白表现出类似于可从肺炎衣原体膜蛋白衍生获得的蛋白的性质特征。这些蛋白包括GGAI的重复基序(至少2个,较佳的至少3个重复序列)和/或保守的色氨酸(w)位置。
比较编码Omp4-15的基因的DNA序列,结果表明,单个基因之间的总体相似性范围在43-55%之间。比较Omp4-15的氨基酸序列结果表明相同性为34-49%,相似性为53-64%。同源性一般沿推导的氨基酸整个长度分散散布。然而,从图8A-J看出,存在一些区域其同源性更明确。这见于重复序列中,其中序列GGAI在基因中重复4-7次。令人感兴趣的是,对于编码四个氨基酸GGAI的序列,DNA同源性并不保守。这可能表明了蛋白该部分的功能性作用,并表明该重复结构并不是由基因复制而产生的。除了四个氨基酸的重复序列GGAI外,氨基酸400-490的区域所具有的同源性要高于该蛋白的其它部分,在所有序列中均有保守序列FYDPI。功能上相似性进一步表明,氨基酸色氨酸(W)在该蛋白C端部分4-6个局部区域完全保守。
由于本发明的基因和推导的氨基酸序列没有一个相同,因此下列内容在本发明的范围内:单特异性抗体的生产,用所述抗体来鉴别哪个肺炎衣原体蛋白被表达,用所述抗体鉴别所述肺炎衣原体蛋白在发育生命周期的何时被表达,用所述抗体鉴定所述肺炎衣原体蛋白的精确的细胞定位。用针对本发明蛋白的单特异性抗体来测定所述蛋白的哪个部分是外露的,肺炎衣原体COMC中的蛋白是怎样相互作用的,这些也在本发明的范围内。
本发明较佳的实例涉及包含本发明蛋白质亚序列的多肽,所述亚序列包含序列GGAI。本发明其它较佳的实例涉及包含本发明蛋白亚序列的多肽,所述亚序列包含序列FSGE。
本发明的多肽的长度通常为至少6个氨基酸,较佳的至少15个氨基酸,较佳的至少20个氨基酸,较佳的至少25个氨基酸,较佳的至少30个氨基酸,较佳的至少35个氨基酸,较佳的至少40个氨基酸,较佳的至少45个氨基酸,较佳的至少50个氨基酸,较佳的至少55个氨基酸,较佳的至少100个氨基酸。
本发明非常重要的一方面涉及本发明衍生自肺炎衣原体的核酸片段,其变体和亚序列。
本发明另一个重要的方面涉及针对本发明蛋白的抗体,这些抗体包括针对具有选自序列SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22和SEQ ID NO:24的蛋白的多克隆单特异性抗体和单克隆抗体。
本发明的一个非常重要的方面涉及用来诊断哺乳动物(如人)感染肺炎衣原体的诊断试剂盒,所述试剂盒包含的一种或多种蛋白具有选自SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22和SEQ ID NO:24的氨基酸序列。
本发明另一非常重要的方面涉及用来诊断哺乳动物(如人)感染肺炎衣原体的诊断试剂盒,所述试剂盒包含针对具有选自SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22和SEQ ID NO:24的氨基酸序列的蛋白的抗体。本发明的诊断试剂盒中包括的抗体可以是多克隆抗体或单克隆抗体或其混合物。
本发明还有一个重要的方面涉及用来诊断哺乳动物(如人)感染肺炎衣原体的诊断试剂盒,所述试剂盒包含具有选自SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQID NO:17、SEQ ID NO:19、SEQ ID NO:21和SEQ ID NO:23的序列的一种或多种核酸片段。
本发明一方面涉及一种用于免疫接种哺乳动物(如人)抵抗肺炎衣原体的组合物,所述组合物包含具有选自SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ IDNO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22和SEQ ID NO:24的氨基酸序列的一种或多种蛋白质。
预计本发明的蛋白在预防哺乳动物(如人)感染肺炎衣原体上有重要作用。因此,通常用重组技术产生本发明的蛋白(包括其变体和亚序列),然后用作免疫接种哺乳动物(如家兔)的抗原。随后,用组织培养试验分析免疫获得的超级免疫血清抵抗肺炎衣原体的保护作用。另外,可以考虑生产单克隆抗体(通常用标准的杂交瘤技术),并分析其抵抗肺炎衣原体感染的保护作用。
预计在本发明的蛋白(包括所述蛋白的亚序列)中可以找到特别感兴趣的和免疫原性表位。较佳的是用包含本发明蛋白的这些亚序列的多肽来免疫哺乳动物(如人)以抵抗肺炎衣原体。
本发明的一个重要的方面涉及下述蛋白在诊断哺乳动物(如人)受肺炎衣原体感染中的应用,该蛋白具有的序列选自SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22和SEQ ID NO:24。
本发明的一个较佳的实例涉及非变性形式的本发明蛋白在诊断哺乳动物(如人)受肺炎衣原体感染中的应用。
本发明的一个非常重要的方面涉及下述蛋白在免疫哺乳动物(如人)抵抗肺炎衣原体中的应用,该蛋白具有的序列选自SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22和SEQ ID NO:24。
本发明的一个较佳的实例涉及非变性形式的本发明蛋白在免疫哺乳动物(如人)抵抗肺炎衣原体中的应用。
本发明的一个非常重要的方面涉及下述核酸片段在免疫哺乳动物(如人)抵抗肺炎衣原体中的应用,该核酸片段具有的核苷酸序列选自SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:21和SEQ ID NO:23。
预计可以开发出一类用基因枪接种小鼠抗肺炎衣原体的疫苗。通常,含有本发明的核酸片段、核酸片段组合的不同基因构建物可用于基因枪方法。随后分析小鼠产生的体液和细胞免疫应答以及在攻击后其抵抗肺炎衣原体感染的保护作用。
鉴于此,本发明还涉及本发明蛋白作为药物(疫苗)的用途以及用来制备抵抗肺炎衣原体感染的疫苗的用途。
含有蛋白序列作为活性组分的疫苗的制备方法是本领域中所熟知的,例子有美国专利4,608,251;4,601,903;4,599,231;4,599,230;4,596,792和4,578,770,所有这些文献均纳入本文作参考。通常,这些疫苗被制成液体溶液或悬浮液形式的可注射剂;还可制成适合在注射液体前溶于溶液或悬浮液的固体形式。制剂还可乳化。活性免疫组分通常和药学上可接受的并与活性组分相容的赋形剂混合。合适的赋形剂例如是水、盐水、葡萄糖、甘油、乙醇等以及它们的组合。另外,如果需要,疫苗还可含有少量辅助物质如润湿剂或乳化剂、pH缓冲剂、或增强疫苗效果的佐剂。
疫苗通常是经肠胃外注射给予,例如皮下注射或肌内注射。适用于其它给药方式的其它制剂包括栓剂以及在一些场合下的口服制剂。这些组合物的形式是溶液、悬浮液、片剂、丸剂、胶囊剂、缓释制剂或粉末,含有10-95%(较佳的为25-70%)的活性组分,并任选地含有合适的载体。
蛋白序列可以本领域已知的中性或盐形式配制入疫苗内。疫苗以相容于剂型的方式给予,其量在治疗上是有效的并且有免疫原性。给药量取决于待治疗的对象。合适的剂量范围为每次接种约几百微克活性组分,较佳的范围约为0.1-1000微克。如果疫苗还包含本领域已知的佐剂物质,则可增强免疫应答。其它可能性包括采用免疫调节物质如淋巴因子(如IFN-γ、IL-2和IL-12)或合成的IFN-γ诱导剂如与上述佐剂组合的聚I:C。
通过下述方式还可产生活疫苗:将编码本发明的蛋白片段或蛋白的至少一个核酸片段导入非病原性微生物中,使蛋白片段或蛋白在微生物表面表达(例如包括膜锚着部分的融合蛋白形式或携带允许锚着到膜上的脂质化(lipidation)信号的略经修饰的蛋白或蛋白片段形式)。技术人员知道怎样使相关表达系统适合此目的。
本发明另一部分依据的事实是,最近的研究揭示,克隆到在载体中的在真核细胞内的非复制性的DNA片段可通过(例如)肌内注射或经皮肤给药(所谓的“基因枪”方法)导入动物(包括人)体内。DNA被肌细胞摄取,感兴趣的基因被在真核细胞内起作用的启动子(例如病毒启动子)表达,随后基因产物刺激免疫系统。Ulmer等人在1993年回顾了这些新发现的方法,该文纳入本文作参考。
因此,编码本发明蛋白的核酸片段可用来实现体内表达抗原,即核酸片段可用作所谓的DNA疫苗。因此,本发明还涉及一种疫苗,它包含编码本发明的蛋白片段或蛋白的核酸片段,该疫苗使已给予疫苗的哺乳动物(如人)在体内表达抗原,表达的抗原量能有效地使哺乳动物(如人)对体内肺炎衣原体感染的抵抗力大大增加。
通过将编码表达产物的基因和编码能调节免疫应答的蛋白的DNA片段一起给予,可以增强这种“DNA疫苗”的效率。例如,通过给予两种分开的DNA片段或给予包含在同一载体中的两种DNA片段,编码淋巴因子前体或淋巴因子(例如IFN-γ、IL-2或IL-12)的基因可以和编码免疫原性蛋白片段或蛋白的基因一同给予。还有一个可能性是给予包含多个核苷酸序列的DNA片段,其中每个核苷酸序列编码本文公开的蛋白片段和蛋白的相对表位,用这些表位的宽谱来实现连续致敏免疫应答。
下列实验为非限制性实施例,目的是为了描述本发明的某些特征和实例。
附图图例
图1显示了负染色的纯化肺炎衣原体EB(A)和纯化的OMC(B)的电镜结果。
图2显示了纯化的EB和OMC银染的15%SDS-PAGE结果。泳道1,纯化的肺炎衣原体EB;泳道2,肺炎衣原体OMC;泳道3,纯化的沙眼衣原体EB;和泳道4,沙眼衣原体OMC。
图3显示了经10%SDS-PAGE分离、转移到硝酸纤维素膜并和家兔抗肺炎衣原体OME血清反应的免疫印迹。
图4显示了经家兔抗肺炎衣原体血清检测的重组pEX的考马斯蓝染色7.5%SDS-PAGE结果。箭头表示117kDaβ半乳糖苷酶蛋白的定位。
图5显示了经菌落印迹检测、7.5%SDS-PAGE分离、转移到硝酸纤维素膜上并和家兔抗肺炎衣原体OMC反应的重组体pEX克隆的免疫印迹。泳道1,海蓝色(seablue)分子量标准。泳道2-6,于42℃培育以诱导产生β半乳糖苷酶融合蛋白的pEX克隆。
图6显示了Omp4和Omp5的序列策略。箭头表示用来测序的引物。
图7。肺炎衣原体omp基因。基因排列在两个簇中。在第1簇中发现Omp12、11、10、5、4、13和14。在第2簇中发现Omp6、7、8、9和15。
图8A-J显示了肺炎衣原体4-15的序列对比,采用GCG软件包中的pile up程序。
图9显示了肺炎衣原体感染的HeLa细胞感染后72小时与针对pEX3-36融合蛋白的小鼠单特异性抗血清反应的免疫荧光。pEX3-36是Omp5基因的一部分。
图10显示了肺炎衣原体EB的免疫印迹。泳道1-3,在SDS-样品缓冲液中加热至100℃,泳道4-6未加热。泳道1和家兔抗肺炎衣原体OMC反应;泳道2和4是前血清(pre-serum);泳道3和5是多克隆家兔抗pEX1-1融合蛋白;泳道6是单克隆抗体26.1。
图11显示了肺炎衣原体的免疫印迹。泳道1-4,在SDS-缓冲液中加热至100℃,泳道5-6未加热。与107CFU的肺炎衣原体感染后14天的C57-黑色小鼠的血清反应。泳道1和5,小鼠1;泳道2和6小鼠2;泳道3和5,小鼠3;泳道4和8,小鼠4。
图12显示了小鼠肺组织的免疫组织学分析,肺炎包涵体存在于支气管上皮组织和肺胞壁中(箭头所指处)。
实施例1
编码98/95kDa肺炎衣原体COMC蛋白的基因的克隆
肺炎衣原体EB和COMC的纯化
在HeLa细胞中培育肺炎衣原体。培育按照Miyashita和Matsumoto(1992)的说明书进行,只是略作修改,以100,000Xg离心上清液和后一次沉淀以及混浊的底层。通过1000xg离心30分钟,使微生物附着于HeLa细胞,然后在5%CO2气氛下在含有5%胎牛血清(FCS,Gibco BRL,Germany目录号10106.169)庆大霉素的RPMI1640培养基(Gibco BRL,Germany目录号51800-27)中37℃培育2小时。将培养基换成另外还含有1毫克/毫升放线菌酮的培养基。培育48小时后,从培养中取出盖玻片,用对肺炎衣原体有特异性的抗体(单克隆抗体26.1)(Christiansen等人,1994)和对种沙眼衣原体有特异性的单克隆抗体(单克隆抗体32.3,Loke diagnostics,ArhusDenmark)测试包涵体,以确保没有发生沙眼衣原体污染。通过Hoechst染色并在BEa和BEg培养基(Freund等人,1979)中培养来测试HeLa细胞中有无支原体污染。另外,通过在BEa和BEg培养基中培育来测试肺炎衣原体原种中有无支原体污染。在培养物或细胞中没有检测到沙眼衣原体、支原体或细菌污染。感染后72小时,以PBS洗涤单层,在PBS中用橡胶刮棒打松细胞,用超声法从宿主细胞中释放出衣原体。在不连续密度梯度上纯化肺炎衣原体EB和RB(Miyashita等人,1992)。用负染色和电子显微镜确认衣原体EB的纯度(图1),只检测到符合肺炎衣原体EB结构的大小为0.3-0.5mm的颗粒。如Caldwell等人(1981)中所述的那样,对纯化的衣原体EB进行十二烷基肌氨酸钠提取,改动之处在于用简单的超声破碎来悬浮COMC。用电子镜和负染色测试纯化的COMC(图1),从中看到折叠的外膜复合物。
SDS-PAGE分析纯化的EB和COMC
在15%SDS-聚丙烯酰胺凝胶上分离纯化的EB和肺炎衣原体OMC中的蛋白,对凝胶银染(图2),在泳道1中看到纯化的EB含有100/95kDa的主要蛋白和38kDa的蛋白,在纯化的COMC(泳道2)中这两种蛋白组也是主要的。另外,分子量为62/60kDa、55kDa和12kDa的蛋白已经在COMC制备物中增浓。在比较纯化的肺炎衣原体EB和纯化的沙眼衣原体EB(泳道3)时,看到沙眼衣原体EB中主要的蛋白是主要外膜蛋白(MOMP),它也是沙眼衣原体COMC制备物(泳道4)中的主要条带,在该制备物中看到60/62kDa的Omp2和12kDa的Omp3。然而没有检测到如同肺炎衣原体COMC制备物的大小为100/95kDa的主要条带。
抗肺炎衣原体COMC的家兔多克隆抗体的产生
为了确保产生在免疫印迹和菌落印迹中识别所有肺炎衣原体蛋白的家兔抗体,将10微克COMC抗原溶解在20微升SDS样品缓冲液中,然后分装在5个小管中。用1毫升PBS和1毫升Freund不完全佐剂(Difco laboratories,USA目录号0639-606)进一步稀释溶解的抗原,并注射新西兰白兔四头肌内。以间隔一周时间肌内注射三次,再过三周,静脉内注射稀释在1毫升PBS中的溶解的COMC蛋白,两周后重复该步骤。在开始免疫后的11周后,从家兔获得血清。用SDS-PAGE分离纯化的肺炎衣原体EB,将蛋白电转移到硝酸纤维素膜上。用多克隆COMC抗体封闭膜并免疫染色(图3)。该血清识别EB制备物中大小为100/95,60和38kDa的蛋白。这与外膜蛋白的大小相符。
COMC蛋白的克隆
由于在HeLa细胞中培育肺炎衣原体,因此EB制备物中可能存在污染性的宿主细胞DNA。因此,用DNA酶处理纯化的EB制备物以除去污染性DNA。然后用CsCl梯度离心纯化肺炎衣原体DNA。用Sau3A部分消化肺炎衣原体DNA,将含有大小约为0.5-0.4kb的DNA片段的级分克隆到表达载体系统pEX(Boehringer,Germany目录号1034 766,1034 774,1034 782)中。pEX载体系统具有β半乳糖苷酶基因,β-半乳糖苷酶基因的3′端有多个克隆位点。基因的表达由PR启动子调节,因此可以通过将温度从32℃升高到42℃来诱导蛋白的表达。将重组细菌菌落转移到硝酸纤维素膜上,将温度升高至42℃2小时。将硝酸纤维素膜置于滤膜上浸泡在5%SDS中,使细菌裂解。用针对肺炎衣原体COMC的多克隆抗体检测表达外膜蛋白的菌落。将阳性克隆培育在悬浮液中并于42℃诱导2小时。用SDS-PAGE分析克隆的蛋白全貌,观察到诱导的β半乳糖苷酶的大小增加(图4)。另外,将蛋白电泳转移到硝酸纤维素膜上,确认与针对COMC的多克隆血清的反应(图5)。
阳性COMC克隆的测序
为了对pEX克隆进行特性分析,对插入的肺炎衣原体DNA测序。在GenEmbl数据库中针对原核序列搜索所得DNA序列。搜索结果鉴定了6个克隆是Omp2基因的部分,2个克隆是Omp3基因的部分,2个克隆是MOMP基因的部分,提示COMC蛋白已经被成功克隆。另外,获得32个克隆,其中含有在GenEmbl数据库中未发现的DNA序列。然而,这些序列可能以两个4-6个克隆的毗连群(contic)簇集,三个克隆是相同的。发现另外19个克隆与该毗连群不重叠(图7)。为了获得关于基因的更多的序列信息,用BamHI限制性酶整个消化肺炎衣原体DNA,将片段克隆到载体pBluescript中。将连接的DNA电转化到大肠杆菌XL1-Blue中,并在含有氨苄青霉素的平板上选择。将重组细菌菌落转移到硝酸纤维素膜上,用pEX1-1克隆的插入物作为探针进行菌落杂交。发现了含有4.5kb的单个BamHI片段的一个克隆,用Southern印迹确认此克隆和探针杂交。用各约为300bp的合成引物对此克隆的插入物进行双向测序。BamHI片段的序列使得其能连接pEX克隆的两个毗连群。和pEX克隆一起总共能装配出编码两个新COMC蛋白的6.5kb DNA序列(图6)。
采用来自已知Omp基因和来自其它已知基因的引物在纯化的肺炎衣原体DNA上进行PCR,获得另外的序列。对获得的PCR产物进行测序。序列结构显示在图7中。检测到另外8个Omp基因。推导的氨基酸序列的序列对比显示在图8A和B中。
DNA序列的分析
DNA序列编码大小为89.6-100.3kDa的Omp4-15蛋白(Omp13为56.1kDa)。Omp4和Omp5以相反方向转录。可能的终止结构位于Omp4下游。Omp5基因的3′端没有被克隆,因为该基因内存在BamHI限制性酶切位点。用GCG软件包(Wisconsin软件包,8.1-UNIX版,1995年8月,序列分析软件包)的gap程序比较Omp4和Omp5的翻译的DNA序列。两个基因的氨基酸相同性为41%(相似性为61%),在Omp4中,信号肽酶1的可能的断裂位点在氨基酸17位,而在Omp5中在氨基酸25位。当将其它两个pEX克隆编码的氨基酸序列与Omp4和Omp5相比时,它们与这些基因也具有氨基酸同源性。发现两个克隆与Omp4和Omp5蛋白中的同一区域有同源性。因此,pEX克隆必定源自另两个基因。因此将这些基因命名为Omp6和Omp7。对其它基因进行类似的分析。与Omp4和Omp5中所见相反,其它推定的Omp蛋白均没有信号肽断裂位点。
实施例2
针对pEX融合蛋白以及加上Omp4的全长重组的多克隆单特异性抗体
为了调查Omp4-7蛋白的拓扑结构,从每个基因中选出代表性的pEX克隆。诱导出β-半乳糖苷酶/Omp的融合蛋白,如同包涵体那样部分纯化。用该抗原以一周的间隔对Balb/c小时肌内免疫三次,6周后获得小鼠血清。用肺炎衣原体感染HeLa细胞。感染72小时后用3.7%甲醛固定单层。由于外膜蛋白被甲醛广泛交联,因此该处理使得抗体不能透过衣原体外膜。用0.2%Triton X100渗透HeLa细胞,用PBS洗涤单层,然后用20%(v/v)FCS培育,以灭活甲醛游离基团。用含20%(v/v)FCS的PBS稀释小鼠血清1∶100,并和单层一起培育半小时。用PBS洗涤单层,加入偶联FITCH的第二家兔抗小鼠血清反应半小时,洗涤单层并固定。一些抗体与包涵体中的EB强烈反应(图9)。尽管作了甲醛固定,但是也不能排除EB表面因处理而改变,这样抗体能到达Omp4-7。因此,用针对克隆pEX3-36的抗体进行免疫电子显微镜法确认反应。将纯化的肺炎衣原体EB吸收到碳涂覆的镍栅格上。吸收后,用PBS洗涤栅格,用溶解在PBS中的0.5%卵白蛋白封闭。用相同缓冲液1∶100稀释抗体,并培育30分钟。用PBS洗涤栅格。在栅格中加入用含1%明胶的PBS稀释的偶联10nm胶体金的家兔抗小鼠Ig,放置半小时。栅格用含1%明胶的PBS洗3次,再用PBS洗3次,栅格用0.7%磷钨酸反染色(contrastain)。在40kV的Jeol 1010电镜中分析栅格。看到金颗粒覆盖了纯化的EB的表面。由于肺炎衣原体EB在纯化或和抗体反应条件下没有接触洗涤剂或固定,因此这些结果表明克隆的蛋白具有外露的表位。
针对Omp4的多克隆单特异性抗体
用含有LIC位点的引物作PCR扩增Omp4基因,将PCR产物克隆到pET-30LIC载体(Novagen)中。通过IPTG诱导合成来表达组氨酸标记的融合蛋白,并在镍柱上纯化。用纯化的Omp4蛋白免疫家兔(6次,每次8微克)。
用针对重组体Omp4的家兔多克隆抗体检测石蜡包埋切片中的肺炎衣原体
在经鼻感染后3天,获得肺炎衣原体感染的小鼠的肺。将组织样品固定在4%甲醛中,用石蜡包埋,切片并在染色前去除石蜡。使切片和以TBS 1∶200稀释的家兔血清室温培育30分钟。在TBS中洗涤两次后,用1∶300稀释于TBS中的第二抗体(生物素化山羊抗家兔抗体)培育切片,然后用TBS洗涤两次。用链霉亲和素-生物素复合物(streptABCompelx/AP,Dako)对切片染色30分钟,洗涤,并在镜检下用chromagen+new fuchsin(Vector Laboratories)显影。用苏木素对切片反染色,用显微镜分析。
用超免疫单特异性家兔抗血清进行免疫印迹分析
用含有LTC位点的引物PCR扩增pEX1-1克隆的插入物。因此,PCR产物能插入pET-32 LIC载体(Novagen,UK目录号69076-1)中。因此,pEX1-1克隆的插入物序列在新载体中以融合蛋白形式表达,由pET-32 LIC载体编码的融合蛋白部分具有一排6个组氨酸残基。在该载体中诱导融合蛋白的表达,由于组氨酸残基对二价阳离子有高亲合力,因此该融合蛋白可在变性条件下在Ni2+柱上纯化。用纯化的蛋白免疫新西兰白色家兔。肌内免疫6次、静脉内免疫2次后,获得家兔血清。将纯化的肺炎衣原体EB溶解在SDS样品缓冲液中。一半样品在样品缓冲液中加热至100℃,而另一半样品则不加热。用SDS-PAGE分离样品,将蛋白转移到硝酸纤维素膜上,使血清和条带反应。对于加热至100℃的样品,血清识别约98kDa的高分子量条带。这与Omp5的预计大小相符,pEX1-1克隆是其一部分,然而,当抗体与未加热EB条带反应时,图形是不同的。现在发现了大小为75kDa的条带,另外在条带上方还观察到较弱的条带(图1a)。这些数据证明,Omp5需要在SDS-样品缓冲液中煮沸来完全变性,并迁移至从基因产物预计的大小处。当样品未煮沸时,蛋白没有完全变性,更少的SDS与蛋白结合,它具有更具球形的结构,其在丙烯酰胺凝胶中会迁移至更远处。条带图形看上去与用单克隆抗体(MAb26.1)的结果相同(泳道6)(我们以前已经描述过(Christiansen等人,1994)),即与肺炎衣原体EB表面反应,但是抗体不与免疫印迹中SDS完全变性的肺炎衣原体EB反应。
C57黑色小鼠的实验性感染
由于了解到没有煮沸的Omp4-7蛋白的迁移发生改变,我们选择在小鼠受实验性感染后分析针对肺炎衣原体EB的抗体。为了从肺炎衣原体引起的感染获得抗体,在微量乙醚麻醉下用107CFI肺炎衣原体鼻内接种C57黑色小鼠。感染14天后获得血清样品,分析肺的病理学变化。在两个小鼠的肺切片中观察到严重的肺炎,而在第3只小鼠中只发现有少量改变。1∶100稀释小鼠血清,并和溶解在煮沸和没有煮沸的样品缓冲液中的纯化的EB反应。在已加热至100℃的制备物中,来自两只小鼠的血清与60/62kDa条带以及55kDa的较弱条带反应强烈,但是对于大小为Omp4-7的蛋白没有观察到反应(图11)。然而,当血清和未加热过的制备物反应时,它们和大小约为75kDa的宽条带均有强反应。这与未加热制备物中Omp4-7蛋白的大小相符。因此,可以归结为,肺炎衣原体感染后抗体识别的Omp4-7蛋白的表位是不连续的表位,因为抗原完全变性完全破坏了表位。在未加热样品中观察到的75kD蛋白不是Omp2(如Omp2特异性抗体免疫印迹所表明)。
实施例3
肺炎衣原体Omp4-7和鹦鹉热衣原体推定的外膜蛋白(POMP)的比较
Longbottom等人1996年已经公开了鹦鹉热衣原体的98-90kDa的部分序列。他们已经将该家族中5个基因的全序列输入了EMBL数据库。他们已将基因命名为“推定的外膜蛋白”(POMP),因为还未确定它们的精确位置。该家族由两个完全相同的基因组成,这两个基因与这些基因高度同源。他们计算出分子大小为90和91kDa。第5个基因编码98kDa的蛋白。用GCG软件包的pileup程序比较肺炎衣原体Omp4-7蛋白的序列和鹦鹉热衣原体POMP蛋白的序列。氨基酸同源性在51-63%范围内。发现肺炎衣原体Omp4-5蛋白与鹦鹉热衣原体的98kDaPOMP蛋白最相关。令人感兴趣的是,与其它鹦鹉热衣原体基因相比,98kDa的鹦鹉热衣原体POMP蛋白和肺炎衣原体基因更相关。GGAI的重复序列在98kDa POMP蛋白中是保守的,但是在90和91kDa鹦鹉热衣原体POMP蛋白中只有3个GGAI重复序列。对于鹦鹉热衣原体,已经显示,针对这些蛋白的抗体似乎对感染有保护作用。
参考文献
1.Caldwell,HD.,J.Kronhout和J.Schacheter,感染免疫学(Infect.Immun.)31,1161-1176(1981).
2.Campbell,L.A.,M.P Melgosa,D.J.Hamilton,C.-C.Kuo和J.T.Grayston,临床微生物杂志(J.Clinical Microbiol.),30,434-439(1992).
3.Christiansen,G.,和S.Birkelund.欧洲微生物(Eur.Microbiol).1:24-29(1992).
4.Christiansen,G.,L.Φstergaard,和S.Birkelund,第8次人感染国际讨论会,Orfila等人编辑,173-176页,1994.
5.Grayston,J.T.,Kuo,C.-C.,Campbell,L.A.,和Vang,S.-P.Int.J.Syst.Bacteriol.39,88-90(1989).
6.Grayston,J.T.,C.-C.Kuo,S.-P.Wang和J.Altman.1986.N.Engl.J.Med.315,161-168(1986).
7.Kuo,C.C.,L.A.Jackson,L.A.Campbell和J.T.Grayston.临床微生物综述(Clin.Microbiol.Rev.)8,451-461(1995).
8.Longbottom,D.,M.Russell,G.E.Jones,A.Lainson,和A.J.Herring.FEMSMicrobiol.Lett.142,277-281(1996).
9.Melgosa,M.P.,C.-C.Kuo和L.A.Campbell,FEMS Microbiol.Lett.112,199-204(1993).
10.Campbell,L.A.,C.-C.Kuo,S.P.Wang和J.T.Grayston.临床微生物杂志,28,1261-1264(1990).
11.Halme,S.,P.Saikku和H.-M.Surcel.Scand.J.Immunol.45,378-384(1997).
12.Miyashita,N.和A.Matsumoto.临床微生物杂志30,2911-2916(1992).
13.Wang,S.P.和J.T.Grayston,Am.J.Ophtalmol.70,367-374(1970).
14.Freund,E.A.,H.Erno和R.M.Lemcke.支原体的鉴定,377-443页,I.Norris和J.R.Bergen;微生物学方法(Method in Microbiology)13卷,A.P.Inc.London 1979.
序列表
(1)一般信息
(i)申请人
(A)姓名:Svend Birkelund
(B)街道:Dept.of Medical Microbiology and Immunology,
University of Arhus
(C)城市:Arhus C
(D)省份:
(E)国家:Denmark
(F)邮政编码(邮编):8000
(ii)发明名称:肺炎衣原体抗原
(iii)序列数目:30
(iv)计算机可读形式:
(A)记录介质类型:软盘
(B)计算机:IBM兼容型
(C)操作系统:DOS
(D)软件:FastSEQ for Windows Version 2.0
(v)本申请资料:
(A)申请号:
(2)SEQ ID NO:1的信息:
(i)序列特征:
(A)长度:3200碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ix)特征:
(A)名称/关键字:编码序列
(B)位置:205...2987
(D)其它信息:
(xi)序列描述:SEQ ID NO:1:
CAATGTCGAA GAGAGCACTA ACCAGGAAAA TTGCGATTTC ATAAACCCAC TTTATTATTA 60
AATTCTTACT TGCGTCATAT AAAATAGAAA ACTCAGAGAG TCAAGATAAA AATTCTTGAC 120
AGCTGTTTTG TCATCTTTAA CTTGATTTAC TTATTTTGTT TCTATATTGA TGCGAATAGT 180
TCTCTAAAAA ACAAAAGCAT TACC ATG AAG ACT TCG ATT CCT TGG GTT TTA 231
Met Lys Thr Ser Ile Pro Trp Val Leu
1 5
GTT TCC TCC GTG TTA GCT TTC TCA TGT CAC CTA CAG TCA CTA GCT AAC 279
Val Ser Ser Val Leu Ala Phe Ser Cys His Leu Gln Ser Leu Ala Asn
10 15 20 25
GAG GAA CTT TTA TCA CCT GAT GAT AGC TTT AAT GGA AAT ATC GAT TCA 327
Glu Glu Leu Leu Ser Pro Asp Asp Ser Phe Asn Gly Asn Ile Asp Ser
30 35 40
GGA ACG TTT ACT CCA AAA ACT TCA GCC ACA ACA TAT TCT CTA ACA GGA 375
Gly Thr Phe Thr Pro Lys Thr Ser Ala Thr Thr Tyr Ser Leu Thr Gly
45 50 55
GAT GTC TTC TTT TAC GAG CCT GGA AAA GGC ACT CCC TTA TCT GAC AGT 423
Asp Val Phe Phe Tyr Glu Pro Gly Lys Gly Thr Pro Leu Ser Asp Ser
60 65 70
TGT TTT AAG CAA ACC ACG GAC AAT CTT ACC TTC TTG GGG AAC GGT CAT 471
Cys Phe Lys Gln Thr Thr Asp Asn Leu Thr Phe Leu Gly Asn Gly His
75 80 85
AGC TTA ACG TTT GGC TTT ATA GAT GCT GGC ACT CAT GCA GGT GCT GCT 519
Ser Leu Thr Phe Gly Phe Ile Asp Ala Gly Thr His Ala Gly Ala Ala
90 95 100 105
GCA TCT ACA ACA GCA AAT AAG AAT CTT ACC TTC TCA GGG TTT TCC TTA 567
Ala Ser Thr Thr Ala Asn Lys Asn Leu Thr Phe Ser Gly Phe Ser Leu
110 115 120
CTG AGT TTT GAT TCC TCT CCT AGC ACA ACG GTT ACT ACA GGT CAG GGA 615
Leu Ser Phe Asp Ser Ser Pro Ser Thr Thr Val Thr Thr Gly Gln Gly
125 130 135
ACG CTT TCC TCA GCA GGA GGC GTA AAT TTA GAA AAT ATT CGT AAA CTT 663
Thr Leu Ser Ser Ala Gly Gly Val Asn Leu Glu Asn Ile Arg Lys Leu
140 145 150
GTA GTT GCT GGG AAT TTT TCT ACT GCA GAT GGT GGA GCT ATC AAA GGA 711
Val Val Ala Gly Asn Phe Ser Thr Ala Asp Gly Gly Ala Ile Lys Gly
155 160 165
GCG TCT TTC CTT TTA ACT GGC ACT TCT GGA GAT GCT CTT TTT AGT AAC 759
Ala Ser Phe Leu Leu Thr Gly Thr Ser Gly Asp Ala Leu Phe Ser Asn
170 175 180 185
AAC TCT TCA TCA ACA AAG GGA GGA GCA ATT GCT ACT ACA GCA GGC GCT 807
Asn Ser Ser Ser Thr Lys Gly Gly Ala Ile Ala Thr Thr Ala Gly Ala
190 195 200
CGC ATA GCA AAT AAC ACA GGT TAT GTT AGA TTC CTA TCT AAC ATA GCG 855
Arg Ile Ala Asn Asn Thr Gly Tyr Val Arg Phe Leu Ser Asn Ile Ala
205 210 215
TCT ACG TCA GGA GGC GCT ATC GAT GAT GAA GGC ACG TCG ATA CTA TCG 903
Ser Thr Ser Gly Gly Ala Ile Asp Asp Glu Gly Thr Ser Ile Leu Ser
220 225 230
AAC AAC AAA TTT CTA TAT TTT GAA GGG AAT GCA GCG AAA ACT ACT GGC 951
Asn Asn Lys Phe Leu Tyr Phe Glu Gly Asn Ala Ala Lys Thr Thr Gly
235 240 245
GGT GCG ATC TGC AAC ACC AAG GCG AGT GGA TCT CCT GAA CTG ATA ATC 999
Gly Ala Ile Cys Asn Thr Lys Ala Ser Gly Ser Pro Glu Leu Ile Ile
250 255 260 265
TCT AAC AAT AAG ACT CTG ATC TTT GCT TCA AAC GTA GCA GAA ACA AGC 1047
Ser Asn Asn Lys Thr Leu Ile Phe Ala Ser Asn Val Ala Glu Thr Ser
270 275 280
GGT GGC GCC ATC CAT GCT AAA AAG CTA GCC CTT TCC TCT GGA GGC TTT 1095
Gly Gly Ala Ile His Ala Lys Lys Leu Ala Leu Ser Ser Gly Gly Phe
285 290 295
ACA GAG TTT CTA CGA AAT AAT GTC TCA TCA GCA ACT CCT AAG GGG GGT 1143
Thr Glu Phe Leu Arg Asn Asn Val Ser Ser Ala Thr Pro Lys Gly Gly
300 305 310
GCT ATC AGC ATC GAT GCC TCA GGA GAG CTC AGT CTT TCT GCA GAG ACA 1191
Ala Ile Ser Ile Asp Ala Ser Gly Glu Leu Ser Leu Ser Ala Glu Thr
315 320 325
GGA AAC ATT ACC TTT GTA AGA AAT ACC CTT ACA ACA ACC GGA AGT ACC 1239
Gly Asn Ile Thr Phe Val Arg Asn Thr Leu Thr Thr Thr Gly Ser Thr
330 335 340 345
GAT ACT CCT AAA CGT AAT GCG ATC AAC ATA GGA AGT AAC GGG AAA TTC 1287
Asp Thr Pro Lys Arg Asn Ala Ile Asn Ile Gly Ser Asn Gly Lys Phe
350 355 360
ACG GAA TTA CGG GCT GCT AAA AAT CAT ACA ATT TTC TTC TAT GAT CCC 1335
Thr Glu Leu Arg Ala Ala Lys Asn His Thr Ile Phe Phe Tyr Asp Pro
365 370 375
ATC ACT TCA GAA GGA ACC TCA TCA GAC GTA TTG AAG ATA AAT AAC GGC 1383
Ile Thr Ser Glu Gly Thr Ser Ser Asp Val Leu Lys Ile Asn Asn Gly
380 385 390
TCT GCG GGA GCT CTC AAT CCA TAT CAA GGA ACG ATT CTA TTT TCT GGA 1431
Ser Ala Gly Ala Leu Asn Pro Tyr Gln Gly Thr Ile Leu Phe Ser Gly
395 400 405
GAA ACC CTA ACA GCA GAT GAA CTT AAA GTT GCT GAC AAT TTA AAA TCT 1479
Glu Thr Leu Thr Ala Asp Glu Leu Lys Val Ala Asp Asn Leu Lys Ser
410 415 420 425
TCA TTC ACG CAG CCA GTC TCC CTA TCC GGA GGA AAG TTA TTG CTA CAA 1527
Ser Phe Thr Gln Pro Val Ser Leu Ser Gly Gly Lys Leu Leu Leu Gln
430 435 440
AAG GGA GTC ACT TTA GAG AGC ACG AGC TTC TCT CAA GAG GCC GGT TCT 1575
Lys Gly Val Thr Leu Glu Ser Thr Ser Phe Ser Gln Glu Ala Gly Ser
445 450 455
CTC CTC GGC ATG GAT TCA GGA ACG ACA TTA TCA ACT ACA GCT GGG AGT 1623
Leu Leu Gly Met Asp Ser Gly Thr Thr Leu Ser Thr Thr Ala Gly Ser
460 465 470
ATT ACA ATC ACG AAC CTA GGA ATC AAT GTT GAC TCC TTA GGT CTT AAG 1671
Ile Thr Ile Thr Asn Leu Gly Ile Asn Val Asp Ser Leu Gly Leu Lys
475 480 485
CAG CCC GTC AGC CTA ACA GCA AAA GGT GCT TCA AAT AAA GTG ATC GTA 1719
Gln Pro Val Ser Leu Thr Ala Lys Gly Ala Ser Asn Lys Val Ile Val
490 495 500 505
TCT GGG AAG CTC AAC CTG ATT GAT ATT GAA GGG AAC ATT TAT GAA AGT 1767
Ser Gly Lys Leu Asn Leu Ile Asp Ile Glu Gly Asn Ile Tyr Glu Ser
510 515 520
CAT ATG TTC AGC CAT GAC CAG CTC TTC TCT CTA TTA AAA ATC ACG GTT 1815
His Met Phe Ser His Asp Gln Leu Phe Ser Leu Leu Lys Ile Thr Val
525 530 535
GAT GCT GAT GTT GAT ACT AAC GTT GAC ATC AGC AGC CTT ATC CCT GTT 1863
Asp Ala Asp Val Asp Thr Asn Val Asp Ile Ser Ser Leu Ile Pro Val
540 545 550
CCT GCT GAG GAT CCT AAT TCA GAA TAC GGA TTC CAA GGA CAA TGG AAT 1911
Pro Ala Glu Asp Pro Asn Ser Glu Tyr Gly Phe Gln Gly Gln Trp Asn
555 560 565
GTT AAT TGG ACT ACG GAT ACA GCT ACA AAT ACA AAA GAG GCC ACG GCA 1959
Val Asn Trp Thr Thr Asp Thr Ala Thr Asn Thr Lys Glu Ala Thr Ala
570 575 580 585
ACT TGG ACC AAA ACA GGA TTT GTT CCC AGC CCC GAA AGA AAA TCT GCG 2007
Thr Trp Thr Lys Thr Gly Phe Val Pro Ser Pro Glu Arg Lys Ser Ala
590 595 600
TTA GTA TGC AAT ACC CTA TGG GGA GTC TTT ACT GAC ATT CGC TCT CTG 2055
Leu Val Cys Asn Thr Leu Trp Gly Val Phe Thr Asp Ile Arg Ser Leu
605 610 615
CAA CAG CTT GTA GAG ATC GGC GCA ACT GGT ATG GAA CAC AAA CAA GGT 2103
Gln Gln Leu Val Glu Ile Gly Ala Thr Gly Met Glu His Lys Gln Gly
620 625 630
TTC TGG GTT TCC TCC ATG ACG AAC TTC CTG CAT AAG ACT GGA GAT GAA 2151
Phe Trp Val Ser Ser Met Thr Asn Phe Leu His Lys Thr Gly Asp Glu
635 640 645
AAT CGC AAA GGC TTC CGT CAT ACC TCT GGA GGC TAC GTC ATC GGT GGA 2199
Asn Arg Lys Gly Phe Arg His Thr Ser Gly Gly Tyr Val Ile Gly Gly
650 655 660 665
AGT GCT CAC ACT CCT AAA GAC GAC CTA TTT ACC TTT GCG TTC TGC CAT 2247
Ser Ala His Thr Pro Lys Asp Asp Leu Phe Thr Phe Ala Phe Cys His
670 675 680
CTC TTT GCT AGA GAC AAA GAT TGT TTT ATC GCT CAC AAC AAC TCT AGA 2295
Leu Phe Ala Arg Asp Lys Asp Cys Phe Ile Ala His Asn Asn Ser Arg
685 690 695
ACC TAG GGT GGA ACT TTA TTC TTC AAG CAC TCT CAT ACC CTA CAA CCC 2343
Thr Tyr Gly Gly Thr Leu Phe Phe Lys His Ser His Thr Leu Gln Pro
700 705 710
CAA AAC TAT TTG AGA TTA GGA AGA GCA AAG TTT TCT GAA TCA GCT ATA 2391
Gln Asn Tyr Leu Arg Leu Gly Arg Ala Lys Phe Ser Glu Ser Ala Ile
715 720 725
GAA AAA TTC CCT AGG GAA ATT CCC CTA GCC TTG GAT GTC CAA GTT TCG 2439
Glu Lys Phe Pro Arg Glu Ile Pro Leu Ala Leu Asp Val Gln Val Ser
730 735 740 745
TTC AGC CAT TCA GAC AAC CGT ATG GAA ACG CAC TAT ACC TCA TTG CCA 2487
Phe Ser His Ser Asp Asn Arg Met Glu Thr His Tyr Thr Ser Leu Pro
750 755 760
GAA TCC GAA GGT TCT TGG AGC AAC GAG TGT ATA GCT GGT GGT ATC GGC 2535
Glu Ser Glu Gly Ser Trp Ser Asn Glu Cys Ile Ala Gly Gly Ile Gly
765 770 775
CTA GAC CTT CCT TTT GTT CTT TCC AAC CCA CAT CCT CTT TTC AAG ACC 2583
Leu Asp Leu Pro Phe Val Leu Ser Asn Pro His Pro Leu Phe Lys Thr
780 785 790
TTC ATT CCA CAG ATG AAA GTC GAA ATG GTT TAT GTA TCA CAA AAT AGC 2631
Phe Ile Pro Gln Met Lys Val Glu Met Val Tyr Val Ser Gln Asn Ser
795 800 805
TTC TTC GAA AGC TCT AGT GAT GGC CGT GGT TTT AGT ATT GGA AGG CTG 2679
Phe Phe Glu Ser Ser Ser Asp Gly Arg Gly Phe Ser Ile Gly Arg Leu
810 815 820 825
CTT AAC CTC TCG ATT CCT GTG GGT GCG AAA TTC GTG CAG GGG GAT ATC 2727
Leu Asn Leu Ser Ile Pro Val Gly Ala Lys Phe Val Gln Gly Asp Ile
830 835 840
GGA GAT TCC TAC ACC TAT GAT CTC TCA GGA TTC TTT GTT TCC GAT GTC 2775
Gly Asp Ser Tyr Thr Tyr Asp Leu Ser Gly Phe Phe Val Ser Asp Val
845 850 855
TAT CGT AAC AAT CCC CAA TCT ACA GCG ACT CTT GTG ATG AGC CCA GAC 2823
Tyr Arg Asn Asn Pro Gln Ser Thr Ala Thr Leu Val Met Ser Pro Asp
860 865 870
TCT TGG AAA ATT CGC GGT GGC AAT CTT TCA AGA CAG GCA TTT TTA CTG 2871
Ser Trp Lys Ile Arg Gly Gly Asn Leu Ser Arg Gln Ala Phe Leu Leu
875 880 885
AGG GGT AGC AAC AAC TAC GTC TAC AAC TCC AAT TGT GAG CTC TTC GGA 2919
Arg Gly Ser Asn Asn Tyr Val Tyr Asn Ser Asn Cys Glu Leu Phe Gly
890 895 900 905
CAT TAC GCT ATG GAA CTC CGT GGA TCT TCA AGG AAC TAC AAT GTA GAT 2967
His Tyr Ala Met Glu Leu Arg Gly Ser Ser Arg Asn Tyr Asn Val Asp
910 915 920
GTT GGT ACC AAA CTC CGA TT CTAGATTGCT AAAACTCCCT AGTTCTTCTA GGGAG 3022
Val Gly Thr Lys Leu Arg Phe
925
TTTTCTCATA CTTTTAGGGA AATATTTGCT ATAGGGAATG CTTTCCTTGC AAACTGTAAA 3082
AAATAACATT TGTCCCTCTT CAAAAAAGAT TTCTTTTAAT AATTTCTAGT TATAATTTTA 3142
TTTTAAAAAC AGTTAAATAA TTAATAGACA ATAATCTATT CTTATTGACT TCTTTTTT 3200
(2)SEQ ID NO:2的信息:
(i)序列特征:
(A)长度:928氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白质
(v)片段类型:内部
(xi)序列描述:SEQ ID NO:2:
Met Lys Thr Ser Ile Pro Trp Val Leu Val Ser Ser Val Leu Ala Phe
1 5 10 15
Ser Cys His Leu Gln Ser Leu Ala Asn Glu Glu Leu Leu Ser Pro Asp
20 25 30
Asp Ser Phe Asn Gly Asn Ile Asp Ser Gly Thr Phe Thr Pro Lys Thr
35 40 45
Ser Ala Thr Thr Tyr Ser Leu Thr Gly Asp Val Phe Phe Tyr Glu Pro
50 55 60
Gly Lys Gly Thr Pro Leu Ser Asp Ser Cys Phe Lys Gln Thr Thr Asp
65 70 75 80
Asn Leu Thr Phe Leu Gly Asn Gly His Ser Leu Thr Phe Gly Phe Ile
85 90 95
Asp Ala Gly Thr His Ala Gly Ala Ala Ala Ser Thr Thr Ala Asn Lys
100 105 110
Asn Leu Thr Phe Ser Gly Phe Ser Leu Leu Ser Phe Asp Ser Ser Pro
115 120 125
Ser Thr Thr Val Thr Thr Gly Gln Gly Thr Leu Ser Ser Ala Gly Gly
130 135 140
Val Asn Leu Glu Asn Ile Arg Lys Leu Val Val Ala Gly Asn Phe Ser
145 150 155 160
Thr Ala Asp Gly Gly Ala Ile Lys Gly Ala Ser Phe Leu Leu Thr Gly
165 170 175
Thr Ser Gly Asp Ala Leu Phe Ser Asn Asn Ser Ser Ser Thr Lys Gly
180 185 190
Gly Ala Ile Ala Thr Thr Ala Gly Ala Arg Ile Ala Asn Asn Thr Gly
195 200 205
Tyr Val Arg Phe Leu Ser Asn Ile Ala Ser Thr Ser Gly Gly Ala Ile
210 215 220
Asp Asp Glu Gly Thr Ser Ile Leu Ser Asn Asn Lys Phe Leu Tyr Phe
225 230 235 240
Glu Gly Asn Ala Ala Lys Thr Thr Gly Gly Ala Ile Cys Asn Thr Lys
245 250 255
Ala Ser Gly Ser Pro Glu Leu Ile Ile Ser Asn Asn Lys Thr Leu Ile
260 265 270
Phe Ala Ser Asn Val Ala Glu Thr Ser Gly Gly Ala Ile His Ala Lys
275 280 285
Lys Leu Ala Leu Ser Ser Gly Gly Phe Thr Glu Phe Leu Arg Asn Asn
290 295 300
Val Ser Ser Ala Thr Pro Lys Gly Gly Ala Ile Ser Ile Asp Ala Ser
305 310 315 320
Gly Glu Leu Ser Leu Ser Ala Glu Thr Gly Asn Ile Thr Phe Val Arg
325 330 335
Asn Thr Leu Thr Thr Thr Gly Ser Thr Asp Thr Pro Lys Arg Asn Ala
340 345 350
Ile Asn Ile Gly Ser Asn Gly Lys Phe Thr Glu Leu Arg Ala Ala Lys
355 360 365
Asn His Thr Ile Phe Phe Tyr Asp Pro Ile Thr Ser Glu Gly Thr Ser
370 375 380
Ser Asp Val Leu Lys Ile Asn Asn Gly Ser Ala Gly Ala Leu Asn Pro
385 390 395 400
Tyr Gln Gly Thr Ile Leu Phe Ser Gly Glu Thr Leu Thr Ala Asp Glu
405 410 415
Leu Lys Val Ala Asp Asn Leu Lys Ser Ser Phe Thr Gln Pro Val Ser
420 425 430
Leu Ser Gly Gly Lys Leu Leu Leu Gln Lys Gly Val Thr Leu Glu Ser
435 440 445
Thr Ser Phe Ser Gln Glu Ala Gly Ser Leu Leu Gly Met Asp Ser Gly
450 455 460
Thr Thr Leu Ser Thr Thr Ala Gly Ser Ile Thr Ile Thr Asn Leu Gly
465 470 475 480
Ile Asn Val Asp Ser Leu Gly Leu Lys Gln Pro Val Ser Leu Thr Ala
485 490 495
Lys Gly Ala Ser Asn Lys Val Ile Val Ser Gly Lys Leu Asn Leu Ile
500 505 510
Asp Ile Glu Gly Asn Ile Tyr Glu Ser His Met Phe Ser His Asp Gln
515 520 525
Leu Phe Ser Leu Leu Lys Ile Thr Val Asp Ala Asp Val Asp Thr Asn
530 535 540
Val Asp Ile Ser Ser Leu Ile Pro Val Pro Ala Glu Asp Pro Asn Ser
545 550 555 560
Glu Tyr Gly Phe Gln Gly Gln Trp Asn Val Asn Trp Thr Thr Asp Thr
565 570 575
Ala Thr Asn Thr Lys Glu Ala Thr Ala Thr Trp Thr Lys Thr Gly Phe
580 585 590
Val Pro Ser Pro Glu Arg Lys Ser Ala Leu Val Cys Asn Thr Leu Trp
595 600 605
Gly Val Phe Thr Asp Ile Arg Ser Leu Gln Gln Leu Val Glu Ile Gly
610 615 620
Ala Thr Gly Met Glu His Lys Gln Gly Phe Trp Val Ser Ser Met Thr
625 630 635 640
Asn Phe Leu His Lys Thr Gly Asp Glu Asn Arg Lys Gly Phe Arg His
645 650 655
Thr Ser Gly Gly Tyr Val Ile Gly Gly Ser Ala His Thr Pro Lys Asp
660 665 670
Asp Leu Phe Thr Phe Ala Phe Cys His Leu Phe Ala Arg Asp Lys Asp
675 680 685
Cys Phe Ile Ala His Asn Asn Ser Arg Thr Tyr Gly Gly Thr Leu Phe
690 695 700
Phe Lys His Ser His Thr Leu Gln Pro Gln Asn Tyr Leu Arg Leu Gly
705 710 715 720
Arg Ala Lys Phe Ser Glu Ser Ala Ile Glu Lys Phe Pro Arg Glu Ile
725 730 735
Pro Leu Ala Leu Asp Val Gln Val Ser Phe Ser His Ser Asp Asn Arg
740 745 750
Met Glu Thr His Tyr Thr Ser Leu Pro Glu Ser Glu Gly Ser Trp Ser
755 760 765
Asn Glu Cys Ile Ala Gly Gly Ile Gly Leu Asp Leu Pro Phe Val Leu
770 775 780
Ser Asn Pro His Pro Leu Phe Lys Thr Phe Ile Pro Gln Met Lys Val
785 790 795 800
Glu Met Val Tyr Val Ser Gln Asn Ser Phe Phe Glu Ser Ser Ser Asp
805 810 815
Gly Arg Gly Phe Ser Ile Gly Arg Leu Leu Asn Leu Ser Ile Pro Val
820 825 830
Gly Ala Lys Phe Val Gln Gly Asp Ile Gly Asp Ser Tyr Thr Tyr Asp
835 840 845
Leu Ser Gly Phe Phe Val Ser Asp Val Tyr Arg Asn Asn Pro Gln Ser
850 855 860
Thr Ala Thr Leu Val Met Ser Pro Asp Ser Trp Lys Ile Arg Gly Gly
865 870 875 880
Asn Leu Ser Arg Gln Ala Phe Leu Leu Arg Gly Ser Asn Asn Tyr Val
885 890 895
Tyr Asn Ser Asn Cys Glu Leu Phe Gly His Tyr Ala Met Glu Leu Arg
900 905 910
Gly Ser Ser Arg Asn Tyr Asn Val Asp Val Gly Thr Lys Leu Arg Phe
915 920 925
(2)SEQ ID NO:3的信息:
(i)序列特征:
(A)长度:2815碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:3:
ATGAAATCGC AATTTTCCTG GTTAGTGCTC TCTTCGACAT TGGCATGTTT TACTAGTTGT 60
TCCACTGTTT TTGCTGCAAC TGCTGAAAAT ATAGGCCCCT CTGATAGCTT TGACGGAAGT 120
ACTAACACAG GCACCTATAC TCCTAAAAAT ACGACTACTG GAATAGACTA TACTCTGACA 180
GGAGATATAA CTCTGCAAAA CCTTGGGGAT TCGGCAGCTT TAACGAAGGG TTGTTTTTCT 240
GACACTACGG AATCTTTAAG CTTTGCCGGT AAGGGGTACT CACTTTCTTT TTTAAATATT 300
AAGTCTAGTG CTGAAGGCGC AGCACTTTCT GTTACAACTG ATAAAAATCT GTCGCTAACA 360
GGATTTTCGA GTCTTACTTT CTTAGCGGCC CCATCATCGG TAATCACAAC CCCCTCAGGA 420
AAAGGTGCAG TTAAATGTGG AGGGGATCTT ACATTTGATA ACAATGGAAC TATTTTATTT 480
AAACAAGATT ACTGTGAGGA AAATGGCGGA GCCATTTCTA CCAAGAATCT TTCTTTGAAA 540
AACAGCACGG GATCGATTTC TTTTGAAGGG AATAAATCGA GCGCAACAGG GAAAAAAGGT 600
GGGGCTATTT GTGCTACTGG TACTGTAGAT ATTACAAATA ATACGGCTCC TACCCTCTTC 660
TCGAACAATA TTGCTGAAGC TGCAGGTGGA GCTATAAATA GCACAGGAAA CTGTACAATT 720
ACAGGGAATA CGTCTCTTGT ATTTTCTGAA AATAGTGTGA CAGCGACCGC AGGAAATGGA 780
GGAGCTCTTT CTGGAGATGC CGATGTTACC ATATCTGGGA ATCAGAGTGT AACTTTCTCA 840
GGAAACCAAG CTGTAGCTAA TGGCGGAGCC ATTTATGCTA AGAAGCTTAC ACTGGCTTCC 900
GGGGGGGGGG GGGGTATCTC CTTTTCTAAC AATATAGTCC AAGGTACCAC TGCAGGTAAT 960
GGTGGAGCCA TTTCTATACT GGCAGCTGGA GAGTGTAGTC TTTCAGCAGA AGCAGGGGAC 1020
ATTACCTTCA ATGGGAATGC CATTGTTGCA ACTACACCAC AAACTACAAA AAGAAATTCT 1080
ATTGACATAG GATCTACTGC AAAGATCACG AATTTACGTG CAATATCTGG GCATAGCATC 1140
TTTTTCTACG ATCCGATTAC TGCTAATACG GCTGCGGATT CTACAGATAC TTTAAATCTC 1200
AATAAGGCTG ATGCAGGTAA TAGTACAGAT TATAGTGGGT CGATTGTTTT TTCTGGTGAA 1260
AAGCTCTCTG AAGATGAAGC AAAAGTTGCA GACAACCTCA CTTCTACGCT GAAGCAGCCT 1320
GTAACTCTAA CTGCAGGAAA TTTAGTACTT AAACGTGGTG TCACTCTCGA TACGAAAGGC 1380
TTTACTCAGA CCGCGGGTTC CTCTGTTATT ATGGATGCGG GCACAACGTT AAAAGCAAGT 1440
ACAGAGGAGG TCACTTTAAC AGGTCTTTCC ATTCCTGTAG ACTCTTTAGG CGAGGGTAAG 1500
AAAGTTGTAA TTGCTGCTTC TGCAGCAAGT AAAAATGTAG CCCTTAGTGG TCCGATTCTT 1560
CTTTTGGATA ACCAAGGGAA TGCTTATGAA AATCACGACT TAGGAAAAAC TCAAGACTTT 1620
TCATTTGTGC AGCTCTCTGC TCTGGGTACT GCAACAACTA CAGATGTTCC AGCGGTTCCT 1680
ACAGTAGCAA CTCCTACGCA CTATGGGTAT CAAGGTACTT GGGGAATGAC TTGGGTTGAT 1740
GATACCGCAA GCACTCCAAA GACTAAGACA GCGACATTAG CTTGGACCAA TACAGGCTAC 1800
CTTCCGAATC CTGAGCGTCA AGGACCTTTA GTTCCTAATA GCCTTTGGGG ATCTTTTTCA 1860
GACATCCAAG CGATTCAAGG TGTCATAGAG AGAAGTGCTT TGACTCTTTG TTCAGATCGA 1920
GGCTTCTGGG CTGCGGGAGT CGCCAATTTC TTAGATAAAG ATAAGAAAGG GGAAAAACGC 1980
AAATACCGTC ATAAATCTGG TGGATATGCT ATCGGAGGTG CAGCGCAAAC TTGTTCTGAA 2040
AACTTAATTA GCTTTGCCTT TTGCCAACTC TTTGGTAGCG ATAAAGATTT CTTAGTCGCT 2100
AAAAATCATA CTGATACCTA TGCAGGAGCC TTCTATATCC AACACATTAC AGAATGTAGT 2160
GGGTTCATAG GTTGTCTCTT AGATAAACTT CCTGGCTCTT GGAGTCATAA ACCCCTCGTT 2220
TTAGAAGGGC AGCTCGCTTA TAGCCACGTC AGTAATGATC TGAAGACAAA GTATACTGCG 2280
TATCCTGAGG TGAAAGGTTC TTGGGGGAAT AATGCTTTTA ACATGATGTT GGGAGCTTCT 2340
TCTCATTCTT ATCCTGAATA CCTGCATTGT TTTGATACCT ATGCTCCATA CATCAAACTG 2400
AATCTGACCT ATATACGTCA GGACAGCTTC TCGGAGAAAG GTACAGAAGG AAGATCTTTT 2460
GATGACAGCA ACCTCTTCAA TTTATCTTTG CCTATAGGGG TGAAGTTTGA GAAGTTCTCT 2520
GATTGTAATG ACTTTTCTTA TGATCTGACT TTATCCTATG TTCCTGATCT TATCCGCAAT 2580
GATCCCAAAT GCACTACAGC ACTTGTAATC AGCGGAGCCT CTTGGGAAAC TTATGCCAAT 2640
AACTTAGCAC GACAGGCCTT GCAAGTGCGT GCAGGCAGTC ACTACGCCTT CTCTCCTATG 2700
TTTGAAGTGC TCGGCCAGTT TGTCTTTGAA GTTCGTGGAT CCTCACGGAT TTATAATGTA 2760
GATCTTGGGG GTAAGTTCCA ATTCTAGGAG CGTCTCTCAT GTCTCAGAAA TTCTG 2815
(2)SEQ ID NO:4的信息:
(i)序列特征:
(A)长度:928氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:4:
Met Lys Ser Gln Phe Ser Trp Leu Val Leu Ser Ser Thr Leu Ala Cys
1 5 10 1 5
Phe Thr Ser Cys Ser Thr Val Phe Ala Ala Thr Ala Glu Asn Ile Gly
20 25 30
Pro Ser Asp Ser Phe Asp Gly Ser Thr Asn Thr Gly Thr Tyr Thr Pro
35 40 45
Lys Asn Thr Thr Thr Gly Ile Asp Tyr Thr Leu Thr Gly Asp Ile Thr
50 55 60
Leu Gln Asn Leu Gly Asp Ser Ala Ala Leu Thr Lys Gly Cys Phe Ser
65 70 75 80
Asp Thr Thr Glu Ser Leu Ser Phe Ala Gly Lys Gly Tyr Ser Leu Ser
85 90 95
Phe Leu Asn Ile Lys Ser Ser Ala Glu Gly Ala Ala Leu Ser Val Thr
100 105 110
Thr Asp Lys Asn Leu Ser Leu Thr Gly Phe Ser Ser Leu Thr Phe Leu
115 120 125
Ala Ala Pro Ser Ser Val Ile Thr Thr Pro Ser Gly Lys Gly Ala Val
130 135 140
Lys Cys Gly Gly Asp Leu Thr Phe Asp Asn Asn Gly Thr Ile Leu Phe
145 150 155 160
Lys Gln Asp Tyr Cys Glu Glu Asn Gly Gly Ala Ile Ser Thr Lys Asn
165 170 175
Leu Ser Leu Lys Asn Ser Thr Gly Ser Ile Ser Phe Glu Gly Asn Lys
180 185 190
Ser Ser Ala Thr Gly Lys Lys Gly Gly Ala Ile Cys Ala Thr Gly Thr
195 200 205
Val Asp Ile Thr Asn Asn Thr Ala Pro Thr Leu Phe Ser Asn Asn Ile
210 215 220
Ala Glu Ala Ala Gly Gly Ala Ile Asn Ser Thr Gly Asn Cys Thr Ile
225 230 235 240
Thr Gly Asn Thr Ser Leu Val Phe Ser Glu Asn Ser Val Thr Ala Thr
245 250 255
Ala Gly Asn Gly Gly Ala Leu Ser Gly Asp Ala Asp Val Thr Ile Ser
260 265 270
Gly Asn Gln Ser Val Thr Phe Ser Gly Asn Gln Ala Val Ala Asn Gly
275 280 285
Gly Ala Ile Tyr Ala Lys Lys Leu Thr Leu Ala Ser Gly Gly Gly Gly
290 295 300
Gly Ile Ser Phe Ser Asn Asn Ile Val Gln Gly Thr Thr Ala Gly Asn
305 310 315 320
Gly Gly Ala Ile Ser Ile Leu Ala Ala Gly Glu Cys Ser Leu Ser Ala
325 330 335
Glu Ala Gly Asp Ile Thr Phe Asn Gly Asn Ala Ile Val Ala Thr Thr
340 345 350
Pro Gln Thr Thr Lys Arg Asn Ser Ile Asp Ile Gly Ser Thr Ala Lys
355 360 365
Ile Thr Asn Leu Arg Ala Ile Ser Gly His Ser Ile Phe Phe Tyr Asp
370 375 380
Pro Ile Thr Ala Asn Thr Ala Ala Asp Ser Thr Asp Thr Leu Asn Leu
385 390 395 400
Asn Lys Ala Asp Ala Gly Asn Ser Thr Asp Tyr Ser Gly Ser Ile Val
405 410 415
Phe Ser Gly Glu Lys Leu Ser Glu Asp Glu Ala Lys Val Ala Asp Asn
420 425 430
Leu Thr Ser Thr Leu Lys Gln Pro Val Thr Leu Thr Ala Gly Asn Leu
435 440 445
Val Leu Lys Arg Gly Val Thr Leu Asp Thr Lys Gly Phe Thr Gln Thr
450 455 460
Ala Gly Ser Ser Val Ile Met Asp Ala Gly Thr Thr Leu Lys Ala Ser
465 470 475 480
Thr Glu Glu Val Thr Leu Thr Gly Leu Ser Ile Pro Val Asp Ser Leu
485 490 495
Gly Glu Gly Lys Lys Val Val Ile Ala Ala Ser Ala Ala Ser Lys Asn
500 505 510
Val Ala Leu Ser Gly Pro Ile Leu Leu Leu Asp Asn Gln Gly Asn Ala
515 520 525
Tyr Glu Asn His Asp Leu Gly Lys Thr Gln Asp Phe Ser Phe Val Gln
530 535 540
Leu Ser Ala Leu Gly Thr Ala Thr Thr Thr Asp Val Pro Ala Val Pro
545 550 555 560
Thr Val Ala Thr Pro Thr His Tyr Gly Tyr Gln Gly Thr Trp Gly Met
565 570 575
Thr Trp Val Asp Asp Thr Ala Ser Thr Pro Lys Thr Lys Thr Ala Thr
580 585 590
Leu Ala Trp Thr Asn Thr Gly Tyr Leu Pro Asn Pro Glu Arg Gln Gly
595 600 605
Pro Leu Val Pro Asn Ser Leu Trp Gly Ser Phe Ser Asp Ile Gln Ala
610 615 620
Ile Gln Gly Val Ile Glu Arg Ser Ala Leu Thr Leu Cys Ser Asp Arg
625 630 635 640
Gly Phe Trp Ala Ala Gly Val Ala Asn Phe Leu Asp Lys Asp Lys Lys
645 650 655
Gly Glu Lys Arg Lys Tyr Arg His Lys Ser Gly Gly Tyr Ala Ile Gly
660 665 670
Gly Ala Ala Gln Thr Cys Ser Glu Asn Leu Ile Ser Phe Ala Phe Cys
675 680 685
Gln Leu Phe Gly Ser Asp Lys Asp Phe Leu Val Ala Lys Asn His Thr
690 695 700
Asp Thr Tyr Ala Gly Ala Phe Tyr Ile Gln His Ile Thr Glu Cys Ser
705 710 715 720
Gly Phe Ile Gly Cys Leu Leu Asp Lys Leu Pro Gly Ser Trp Ser His
725 730 735
Lys Pro Leu Val Leu Glu Gly Gln Leu Ala Tyr Ser His Val Ser Asn
740 745 750
Asp Leu Lys Thr Lys Tyr Thr Ala Tyr Pro Glu Val Lys Gly Ser Trp
755 760 765
Gly Asn Asn Ala Phe Asn Met Met Leu Gly Ala Ser Ser His Ser Tyr
770 775 780
Pro Glu Tyr Leu His Cys Phe Asp Thr Tyr Ala Pro Tyr Ile Lys Leu
785 790 795 800
Asn Leu Thr Tyr Ile Arg Gln Asp Ser Phe Ser Glu Lys Gly Thr Glu
805 810 815
Gly Arg Ser Phe Asp Asp Ser Asn Leu Phe Asn Leu Ser Leu Pro Ile
820 825 830
Gly Val Lys Phe Glu Lys Phe Ser Asp Cys Asn Asp Phe Ser Tyr Asp
835 840 845
Leu Thr Leu Ser Tyr Val Pro Asp Leu Ile Arg Asn Asp Pro Lys Cys
850 855 860
Thr Thr Ala Leu Val Ile Ser Gly Ala Ser Trp Glu Thr Tyr Ala Asn
865 870 875 880
Asn Leu Ala Arg Gln Ala Leu Gln Val Arg Ala Gly Ser His Tyr Ala
885 890 895
Phe Ser Pro Met Phe Glu Val Leu Gly Gln Phe Val Phe Glu Val Arg
900 905 910
Gly Ser Ser Arg Ile Tyr Asn Val Asp Leu Gly Gly Lys Phe Gln Phe
915 920 925
(2)SEQ ID NO:5的信息:
(i)序列特征:
(A)长度:3052碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:5:
ATGCGATTTT CGCTCTGCGG ATTTCCTCTA GTTTTTTCTT TAACATTGCT CTCAGTCTTC 60
GACACTTCTT TGAGTGCTAC TACGATTTCT TTAACCCCAG AAGATAGTTT TCATGGAGAT 120
AGTCAGAATG CAGAACGTTC TTATAATGTT CAAGCTGGGG ATGTCTATAG CCTTACTGGT 180
GATGTCTCAA TATCTAACGT CGATAACTCT GCATTAAATA AAGCCTGCTT CAATGTGACC 240
TCAGGAAGTG TGACGTTCGC AGGAAATCAT CATGGGTTAT ATTTTAATAA TATTTCCTCA 300
GGAACTACAA AGGAAGGGGC TGTACTTTGT TGCCAAGATC CTCAAGCAAC GGCACGTTTT 360
TCTGGGTTCT CCACGCTCTC TTTTATTCAG AGCCCCGGAG ATATTAAAGA ACAGGGATGT 420
CTCTATTCAA AAAATGCACT TATGCTCTTA AACAATTATG TAGTGCGTTT TGAACAAAAC 480
CAAAGTAAGA CTAAAGGCGG AGCTATTAGT GGGGCGAATG TTACTATAGT AGGCAACTAC 540
GATTCCGTCT CTTTCTATCA GAATGCAGCC ACTTTTGGAG GTGCTATCCA TTCTTCAGGT 600
CCCCTACAGA TTGCAGTAAA TCAGGCAGAG ATAAGATTTG CACAAAATAC TGCCAAGAAT 660
GGTTCTGGAG GGGCTTTGTA CTCCGATGGT GATATTGATA TTGATCAGAA TGCTTATGTT 720
CTATTTCGAG AAAATGAGGC ATTGACTACT GCTATAGGTA AGGGAGGGGC TGTCTGTTGT 780
CTTCCCACTT CAGGAAGTAG TACTCCAGTT CCTATTGTGA CTTTCTCTGA CAATAAACAG 840
TTAGTCTTTG AAAGAAACCA TTCCATAATG GGTGGCGGAG CCATTTATGC TAGGAAACTT 900
AGCATCTCTT CAGGAGGTCC TACTCTATTT ATCAATAATA TATCATATGC AAATTCGCAA 960
AATTTAGGTG GAGCTATTGC CATTGATACT GGAGGGGAGA TCAGTTTATC AGCAGAGAAA 1020
GGAACAATTA CATTCCAAGG AAACCGGACG AGCTTACCGT TTTTGAATGG CATCCATCTT 1080
TTACAAAATG CTAAATTCCT GAAATTACAG GCGAGAAATG GATGCTCTAT AGAATTTTAT 1140
GATCCTATTA CTTCTGAAGC AGATGGGTCT ACCCAATTGA ATATCAACGG AGATCCTAAA 1200
AATAAAGAGT ACACAGGGAC CATACTCTTT TCTGGAGAAA AGAGTCTAGC AAACGATCCT 1260
AGGGATTTTA AATCTACAAT CCCTCAGAAC GTCAACCTGT CTGCAGGATA CTTAGTTATT 1320
AAAGAGGGGG CCGAAGTCAC AGTTTCAAAA TTCACGCAGT CTCCAGGATC GCATTTAGTT 1380
TTAGATTTAG GAACCAAACT GATAGCCTCT AAGGAAGACA TTGCCATCAC AGGCCTCGCG 1440
ATAGATATAG ATAGCTTAAG CTCATCCTCA ACAGCAGCTG TTATTAAAGC AAACACCGCA 1500
AATAAACAGA TATCCGTGAC GGACTCTATA GAACTTATCT CGCCTACTGG CAATGCCTAT 1560
GAAGATCTCA GAATGAGAAA TTCACAGACG TTCCCTCTGC TCTCTTTAGA GCCTGGAGCC 1620
GGGGGTAGTG TGACTGTAAC TGCTGGAGAT TTCCTACCGG TAAGTCCCCA TTATGGTTTT 1680
CAAGGCAATT GGAAATTAGC TTGGACAGGA ACTGGAAACA AAGTTGGAGA ATTCTTCTGG 1740
GATAAAATAA ATTATAAGCC TAGACCTGAA AAAGAAGGAA ATTTAGTTCC TAATATCTTG 1800
TGGGGGAATG CTGTAAATGT CAGATCCTTA ATGCAGGTTC AAGAGACCCA TGCATCGAGC 1860
TTACAGACAG ATCGAGGGCT GTGGATCGAT GGAATTGGGA ATTTCTTCCA TGTATCTGCC 1920
TCCGAAGACA ATATAAGGTA CCGTCATAAC AGCGGTGGAT ATGTTCTATC TGTAAATAAT 1980
GAGATCACAC CTAAGCACTA TACTTCGATG GCATTTTCCC AACTCTTTAG TAGAGACAAG 2040
GACTATGCGG TTTCCAACAA CGAATACAGA ATGTATTTAG GATCGTATCT CTATCAATAT 2100
ACAACCTCCC TAGGGAATAT TTTCCGTTAT GCTTCGCGTA ACCCTAATGT AAACGTCGGG 2160
ATTCTCTCAA GAAGGTTTCT TCAAAATCCT CTTATGATTT TTCATTTTTT GTGTGCTTAT 2220
GGTCATGCCA CCAATGATAT GAAAACAGAC TACGCAAATT TCCCTATGGT GAAAAACAGC 2280
TGGAGAAACA ATTGTTGGGC TATAGAGTGC GGAGGGAGCA TGCCTCTATT GGTATTTGAG 2340
AACGGAAGAC TTTTCCAAGG TGCCATCCCA TTTATGAAAC TACAATTAGT TTATGCTTAT 2400
CAGGGAGATT TCAAAGAGAC GACTGCAGAT GGCCGTAGAT TTAGTAATGG GAGTTTAACA 2460
TCGATTTCTG TACCTCTAGG CATACGCTTT GAGAAGCTGG CACTTTCTCA GGATGTACTC 2520
TATGACTTTA GTTTCTCCTA TATTCCTGAT ATTTTCCGTA AGGATCCCTC ATGTGAAGCT 2580
GCTCTGGTGA TTAGCGGAGA CTCCTGGCTT GTTCCGGCAG CACACGTATC AAGACATGCT 2640
TTTGTAGGGA GTGGAACGGG TCGGTATCAC TTTAACGACT ATACTGAGCT CTTATGTCGA 2700
GGAAGTATAG AATGCCGCCC CCATGCTAGG AATTATAATA TAAACTGTGG AAGCAAATTT 2760
CGTTTTTAGA AGGTTTCCAT TGCCTGTGTG GTTCCGGATC TTAACTATAA ATCCTGGACT 2820
ATGGATCATA GGCATTGGGT TTCTCGAACT TGTGTGGAGA ATAACGACAT TTTATATGCA 2880
TAACGGAATA CTCGTATCAC CTCAGCCCCT AGAGACATTC TTTAGGGGTT CTTTATTTGT 2940
CTAAACTTCG TATTTTATCG AGAATCCTTT ACGTTCTTGG TTTGCTTGTC TCCGAGGAGT 3000
TCTCTAACGA ATCATAGGGA TTCCAGGGTT CTGTTCCTTG AGTCCTTTGG CA 3052
(2)SEQ ID NO:6的信息:
(i)序列特征:
(A)长度:922氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:6:
Met Arg Phe Ser Leu Cys Gly Phe Pro Leu Val Phe Ser Leu Thr Leu
1 5 10 15
Leu Ser Val Phe Asp Thr Ser Leu Ser Ala Thr Thr Ile Ser Leu Thr
20 25 30
Pro Glu Asp Ser Phe His Gly Asp Ser Gln Asn Ala Glu Arg Ser Tyr
35 40 45
Asn Val Gln Ala Gly Asp Val Tyr Ser Leu Thr Gly Asp Val Ser Ile
50 55 60
Ser Asn Val Asp Asn Ser Ala Leu Asn Lys Ala Cys Phe Asn Val Thr
65 70 75 80
Ser Gly Ser Val Thr Phe Ala Gly Asn His His Gly Leu Tyr Phe Asn
85 90 95
Asn Ile Ser Ser Gly Thr Thr Lys Glu Gly Ala Val Leu Cys Cys Gln
100 105 110
Asp Pro Gln Ala Thr Ala Arg Phe Ser Gly Phe Ser Thr Leu Ser Phe
115 120 125
Ile Gln Ser Pro Gly Asp Ile Lys Glu Gln Gly Cys Leu Tyr Ser Lys
130 135 140
Asn Ala Leu Met Leu Leu Asn Asn Tyr Val Val Arg Phe Glu Gln Asn
145 150 155 160
Gln Ser Lys Thr Lys Gly Gly Ala Ile Ser Gly Ala Asn Val Thr Ile
165 170 175
Val Gly Asn Tyr Asp Ser Val Ser Phe Tyr Gln Asn Ala Ala Thr Phe
180 185 190
Gly Gly Ala Ile His Ser Ser Gly Pro Leu Gln Ile Ala Val Asn Gln
195 200 205
Ala Glu Ile Arg Phe Ala Gln Asn Thr Ala Lys Asn Gly Ser Gly Gly
210 215 220
Ala Leu Tyr Ser Asp Gly Asp Ile Asp Ile Asp Gln Asn Ala Tyr Val
225 230 235 240
Leu Phe Arg Glu Asn Glu Ala Leu Thr Thr Ala Ile Gly Lys Gly Gly
245 250 255
Ala Val Cys Cys Leu Pro Thr Ser Gly Ser Ser Thr Pro Val Pro Ile
260 265 270
Val Thr Phe Ser Asp Asn Lys Gln Leu Val Phe Glu Arg Asn His Ser
275 280 285
Ile Met Gly Gly Gly Ala Ile Tyr Ala Arg Lys Leu Ser Ile Ser Ser
290 295 300
Gly Gly Pro Thr Leu Phe Ile Asn Asn Ile Ser Tyr Ala Asn Ser Gln
305 310 315 320
Asn Leu Gly Gly Ala Ile Ala Ile Asp Thr Gly Gly Glu Ile Ser Leu
325 330 335
Ser Ala Glu Lys Gly Thr Ile Thr Phe Gln Gly Asn Arg Thr Ser Leu
340 345 350
Pro Phe Leu Asn Gly Ile His Leu Leu Gln Asn Ala Lys Phe Leu Lys
355 360 365
Leu Gln Ala Arg Asn Gly Cys Ser Ile Glu Phe Tyr Asp Pro Ile Thr
370 375 380
Ser Glu Ala Asp Gly Ser Thr Gln Leu Asn Ile Asn Gly Asp Pro Lys
385 390 395 400
Asn Lys Glu Tyr Thr Gly Thr Ile Leu Phe Ser Gly Glu Lys Ser Leu
405 410 415
Ala Asn Asp Pro Arg Asp Phe Lys Ser Thr Ile Pro Gln Asn Val Asn
420 425 430
Leu Ser Ala Gly Tyr Leu Val Ile Lys Glu Gly Ala Glu Val Thr Val
435 440 445
Ser Lys Phe Thr Gln Ser Pro Gly Ser His Leu Val Leu Asp Leu Gly
450 455 460
Thr Lys Leu Ile Ala Ser Lys Glu Asp Ile Ala Ile Thr Gly Leu Ala
465 470 475 480
Ile Asp Ile Asp Ser Leu Ser Ser Ser Ser Thr Ala Ala Val Ile Lys
485 490 495
Ala Asn Thr Ala Asn Lys Gln Ile Ser Val Thr Asp Ser Ile Glu Leu
500 505 510
Ile Ser Pro Thr Gly Asn Ala Tyr Glu Asp Leu Arg Met Arg Asn Ser
515 520 525
Gln Thr Phe Pro Leu Leu Ser Leu Glu Pro Gly Ala Gly Gly Ser Val
530 535 540
Thr Val Thr Ala Gly Asp Phe Leu Pro Val Ser Pro His Tyr Gly Phe
545 550 555 560
Gln Gly Asn Trp Lys Leu Ala Trp Thr Gly Thr Gly Asn Lys Val Gly
565 570 575
Glu Phe Phe Trp Asp Lys Ile Asn Tyr Lys Pro Arg Pro Glu Lys Glu
580 585 590
Gly Asn Leu Val Pro Asn Ile Leu Trp Gly Asn Ala Val Asn Val Arg
595 600 605
Ser Leu Met Gln Val Gln Glu Thr His Ala Ser Ser Leu Gln Thr Asp
610 615 620
Arg Gly Leu Trp Ile Asp Gly Ile Gly Asn Phe Phe His Val Ser Ala
625 630 635 640
Ser Glu Asp Asn Ile Arg Tyr Arg His Asn Ser Gly Gly Tyr Val Leu
645 650 655
Ser Val Asn Asn Glu Ile Thr Pro Lys His Tyr Thr Ser Met Ala Phe
660 665 670
Ser Gln Leu Phe Ser Arg Asp Lys Asp Tyr Ala Val Ser Asn Asn Glu
675 680 685
Tyr Arg Met Tyr Leu Gly Ser Tyr Leu Tyr Gln Tyr Thr Thr Ser Leu
690 695 700
Gly Asn Ile Phe Arg Tyr Ala Ser Arg Asn Pro Asn Val Asn Val Gly
705 710 715 720
Ile Leu Ser Arg Arg Phe Leu Gln Asn Pro Leu Met Ile Phe His Phe
725 730 735
Leu Cys Ala Tyr Gly His Ala Thr Asn Asp Met Lys Thr Asp Tyr Ala
740 745 750
Asn Phe Pro Met Val Lys Asn Ser Trp Arg Asn Asn Cys Trp Ala Ile
755 760 765
Glu Cys Gly Gly Ser Met Pro Leu Leu Val Phe Glu Asn Gly Arg Leu
770 775 780
Phe Gln Gly Ala Ile Pro Phe Met Lys Leu Gln Leu Val Tyr Ala Tyr
785 790 795 800
Gln Gly Asp Phe Lys Glu Thr Thr Ala Asp Gly Arg Arg Phe Ser Asn
805 810 815
Gly Ser Leu Thr Ser Ile Ser Val Pro Leu Gly Ile Arg Phe Glu Lys
820 825 830
Leu Ala Leu Ser Gln Asp Val Leu Tyr Asp Phe Ser Phe Ser Tyr Ile
835 840 845
Pro Asp Ile Phe Arg Lys Asp Pro Ser Cys Glu Ala Ala Leu Val Ile
850 855 860
Ser Gly Asp Ser Trp Leu VaI Pro Ala Ala His Val Ser Arg His Ala
865 870 875 880
Phe Val Gly Ser Gly Thr Gly Arg Tyr His Phe Asn Asp Tyr Thr Glu
885 890 895
Leu Leu Cys Arg Gly Ser Ile Glu Cys Arg Pro His Ala Arg Asn Tyr
900 905 910
Asn Ile Asn Cys Gly Ser Lys Phe Arg Phe
915 920
(2)SEQ ID NO:7的信息:
(i)序列特征:
(A)长度:2526碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:7:
ATGAAGATTC CACTCCGCTT TTTATTGATA TCATTAGTAC CTACGCTTTC TATGTCGAAT 60
TTATTAGGAG CTGCTACTAC CGAAGAGCTA TCGGCTAGCA ATAGCTTCGA TGGAACTACA 120
TCAACAACAA GCTTTTCTAG TAAAACATCA TCGGCTACAG ATGGCACCAA TTATGTTTTT 180
AAAGATTCTG TAGTTATAGA AAATGTACCC AAAACAGGGG AAACTCAGTC TACTAGTTGT 240
TTTAAAAATG ACGCTGCAGC TGGAGATCTA AATTTCTTAG GAGGGGGATT TTCTTTCACA 300
TTTAGCAATA TCGATGCAAC CACGGCTTCT GGAGCTGCTA TTGGAAGTGA AGCAGCTAAT 360
AAGACAGTCA CGTTATCAGG ATTTTCGGCA CTTTCTTTTC TTAAATCCCC AGCAAGTACA 420
GTGACTAATG GATTGGGAGC TATCAATGTT AAAGGGAATT TAAGCCTATT GGATAATGAT 480
AAGGTATTGA TTCAGGACAA TTTCTCAACA GGAGATGGCG GAGCAATTAA TTGTGCAGGC 540
TCCTTGAAGA TCGCAAACAA TAAGTCCCTT TCTTTTATTG GAAATAGTTC TTCAACACGT 600
GGCGGAGCGA TTCATACCAA AAACCTCACA CTATCTTCTG GTGGGGAAAC TCTATTTCAG 660
GGGAATACAG CGCCTACGGC TGCTGGTAAA GGAGGTGCTA TCGCGATTGC AGACTCTGGC 720
ACCCTATCCA TTTCTGGAGA CAGTGGCGAC ATTATCTTTG AAGGCAATAC GATAGGAGCT 780
ACAGGAACCG TCTCTCATAG TGCTATTGAT TTAGGAACTA GCGCTAAGAT AACTGCGTTA 840
CGTGCTGCGC AAGGACATAC GATATACTTT TATGATCCGA TTACTGTAAC AGGATCGACA 900
TCTGTTGCTG ATGCTCTCAA TATTAATAGC CCTGATACTG GAGATAACAA AGAGTATACG 960
GGAACCATAG TCTTTTCTGG AGAGAAGCTC ACGGAGGCAG AAGCTAAAGA TGAGAAGAAC 1020
CGCACTTCTA AATTACTTCA AAATGTTGCT TTTAAAAATG GGACTGTAGT TTTAAAAGGT 1080
GATGTCGTTT TAAGTGCGAA CGGTTTCTCT CAGGATGCAA ACTCTAAGTT GATTATGGAT 1140
TTAGGGACGT CGTTGGTTGC AAACACCGAA AGTATCGAGT TAACGAATTT GGAAATTAAT 1200
ATAGACTCTC TCAGGAACGG GAAAAAGATA AAACTCAGTG CTGCCACAGC TCAGAAAGAT 1260
ATTCGTATAG ATCGTCCTGT TGTACTGGCA ATTAGCGATG AGAGTTTTTA TCAAAATGGC 1320
TTTTTGAATG AGGACCATTC CTATGATGGG ATTCTTGAGT TAGATGCTGG GAAAGACATC 1380
GTGATTTCTG CAGATTCTCG CAGTATAAAT GCTGTACAAT CTCCGTATGG CTATCAGGGA 1440
AAGTGGACAA TCAATTGGTC TACTGATGAT AAGAAAGCTA CGGTTTCTTG GGCAAAGCAA 1500
AGTTTTAATC CCACTGCTGA GCAGGAGGCT CCGTTAGTTC CTAATCTTCT TTGGGGTTCT 1560
TTTATAGATG TTCGTCCCTT CCAAAATTTT ATAGAGCTAG GTACTGAAGG TGCTCCTTAC 1620
GAAAAGAGAT TTTGGGTTGC AGGCATTTCC AATGTTTTGC ATAGGAGCGG TCGTGAAAAT 1680
CAAAGGAAAT TCCGTCATGT GAGTGGAGGT GCTGTAGTAG GTGCTAGCAC GAGGATGCCG 1740
GGTGGTGATA CCTTGTCTCT GGGTTTTGCT CAGCTCTTTG CGCGTGACAA AGACTACTTT 1800
ATGAATACCA ATTTCGCAAA GACCTACGCA GGATCTTTAC GTTTGCAGCA CGATGCTTCC 1860
CTATACTCTG TGGTGAGTAT CCTTTTAGGA GAGGGAGGAC TCCGCGAGAT CCTGTTGCCT 1920
TATGTTTCCA AGACTCTGCC GTGCTCTTTC TATGGGCAGC TTAGCTACGG CCATACGGAT 1980
CATCGCATGA AGACCGAGTC TCTACCCCCC CCCCCCCCGA CGCTCTCGAC GGATCATACT 2040
TCTTGGGGAG GATATGTCTG GGCTGGAGAG CTGGGAACTC GAGTTGCTGT TGAAAATACC 2100
AGCGGCAGAG GATTTTTCCG AGAGTACACT CCATTTGTAA AAGTCCAAGC TGTTTACTCG 2160
CGCCAAGATA GCTTTGTTGA ACTAGGAGCT ATCAGTCGTG ATTTTAGTGA TTCGCATCTT 2220
TATAACCTTG CGATTCCTCT TGGAATCAAG TTAGAGAAAC GGTTTGCAGA GCAATATTAT 2280
CATGTTGTAG CGATGTATTC TCCAGATGTT TGTCGTAGTA ACCCCAAATG TACGACTACC 2340
CTACTTTCCA ACCAAGGGAG TTGGAAGACC AAAGGTTCGA ACTTAGCAAG ACAGGCTGGT 2400
ATTGTTCAGG CCTCAGGTTT TCGATCTTTG GGAGCTGCAG CAGAGCTTTT CGGGAACTTT 2460
GGCTTTGAAT GGCGGGGATC TTCTCGTAGC TATAATGTAG ATGCGGGTAG CAAAATCAAA 2520
TTTTAG 2526
(2)SEQ ID NO:8的信息:
(i)序列特征:
(A)长度:841氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:8:
Met Lys Ile Pro Leu Arg Phe Leu Leu Ile Ser Leu Val Pro Thr Leu
1 5 10 15
Ser Met Ser Asn Leu Leu Gly Ala Ala Thr Thr Glu Glu Leu Ser Ala
20 25 30
Ser Asn Ser Phe Asp Gly Thr Thr Ser Thr Thr Ser Phe Ser Ser Lys
35 40 45
Thr Ser Ser Ala Thr Asp Gly Thr Asn Tyr Val Phe Lys Asp Ser Val
50 55 60
Val Ile Glu Asn Val Pro Lys Thr Gly Glu Thr Gln Ser Thr Ser Cys
65 70 75 80
Phe Lys Asn Asp Ala Ala Ala Gly Asp Leu Asn Phe Leu Gly Gly Gly
85 90 95
Phe Ser Phe Thr Phe Ser Asn Ile Asp Ala Thr Thr Ala Ser Gly Ala
100 105 110
Ala Ile Gly Ser Glu Ala Ala Asn Lys Thr Val Thr Leu Ser Gly Phe
115 120 125
Ser Ala Leu Ser Phe Leu Lys Ser Pro Ala Ser Thr Val Thr Asn Gly
130 135 140
Leu Gly Ala Ile Asn Val Lys Gly Asn Leu Ser Leu Leu Asp Asn Asp
145 150 155 160
Lys Val Leu Ile Gln Asp Asn Phe Ser Thr Gly Asp Gly Gly Ala Ile
165 170 175
Asn Cys Ala Gly Ser Leu Lys Ile Ala Asn Asn Lys Ser Leu Ser Phe
180 185 190
Ile Gly Asn Ser Ser Ser Thr Arg Gly Gly Ala Ile His Thr Lys Asn
195 200 205
Leu Thr Leu Ser Ser Gly Gly Glu Thr Leu Phe Gln Gly Asn Thr Ala
210 215 220
Pro Thr Ala Ala Gly Lys Gly Gly Ala Ile Ala Ile Ala Asp Ser Gly
225 230 235 240
Thr Leu Ser Ile Ser Gly Asp Ser Gly Asp Ile Ile Phe Glu Gly Asn
245 250 255
Thr Ile Gly Ala Thr Gly Thr Val Ser His Ser Ala Ile Asp Leu Gly
260 265 270
Thr Ser Ala Lys Ile Thr Ala Leu Arg Ala Ala Gln Gly His Thr Ile
275 280 285
Tyr Phe Tyr Asp Pro Ile Thr Val Thr Gly Ser Thr Ser Val Ala Asp
290 295 300
Ala Leu Asn Ile Asn Ser Pro Asp Thr Gly Asp Asn Lys Glu Tyr Thr
305 310 315 320
Gly Thr Ile Val Phe Ser Gly Glu Lys Leu Thr Glu Ala Glu Ala Lys
325 330 335
Asp Glu Lys Asn Arg Thr Ser Lys Leu Leu Gln Asn Val Ala Phe Lys
340 345 350
Asn Gly Thr Val Val Leu Lys Gly Asp Val Val Leu Ser Ala Asn Gly
355 360 365
Phe Ser Gln Asp Ala Asn Ser Lys Leu Ile Met Asp Leu Gly Thr Ser
370 375 380
Leu Val Ala Asn Thr Glu Ser Ile Glu Leu Thr Asn Leu Glu Ile Asn
385 390 395 400
Ile Asp Ser Leu Arg Asn Gly Lys Lys Ile Lys Leu Ser Ala Ala Thr
405 410 415
Ala Gln Lys Asp Ile Arg Ile Asp Arg Pro Val Val Leu Ala Ile Ser
420 425 430
Asp Glu Ser Phe Tyr Gln Asn Gly Phe Leu Asn Glu Asp His Ser Tyr
435 440 445
Asp Gly Ile Leu Glu Leu Asp Ala Gly Lys Asp Ile Val Ile Ser Ala
450 455 460
Asp Ser Arg Ser Ile Asn Ala Val Gln Ser Pro Tyr Gly Tyr Gln Gly
465 470 475 480
Lys Trp Thr Ile Asn Trp Ser Thr Asp Asp Lys Lys Ala Thr Val Ser
485 490 495
Trp Ala Lys Gln Ser Phe Asn Pro Thr Ala Glu Gln Glu Ala Pro Leu
500 505 510
Val Pro Asn Leu Leu Trp Gly Ser Phe Ile Asp Val Arg Pro Phe Gln
515 520 525
Asn Phe Ile Glu Leu Gly Thr Glu Gly Ala Pro Tyr Glu Lys Arg Phe
530 535 540
Trp Val Ala Gly Ile Ser Asn Val Leu His Arg Ser Gly Arg Glu Asn
545 550 555 560
Gln Arg Lys Phe Arg His Val Ser Gly Gly Ala Val Val Gly Ala Ser
565 570 575
Thr Arg Met Pro Gly Gly Asp Thr Leu Ser Leu Gly Phe Ala Gln Leu
580 585 590
Phe Ala Arg Asp Lys Asp Tyr Phe Met Asn Thr Asn Phe Ala Lys Thr
595 600 605
Tyr Ala Gly Ser Leu Arg Leu Gln His Asp Ala Ser Leu Tyr Ser Val
610 615 620
Val Ser Ile Leu Leu Gly Glu Gly Gly Leu Arg Glu Ile Leu Leu Pro
625 630 635 640
Tyr Val Ser Lys Thr Leu Pro Cys Ser Phe Tyr Gly Gln Leu Ser Tyr
645 650 655
Gly His Thr Asp His Arg Met Lys Thr Glu Ser Leu Pro Pro Pro Pro
660 665 670
Pro Thr Leu Ser Thr Asp His Thr Ser Trp Gly Gly Tyr Val Trp Ala
675 680 685
Gly Glu Leu Gly Thr Arg Val Ala Val Glu Asn Thr Ser Gly Arg Gly
690 695 700
Phe Phe Arg Glu Tyr Thr Pro Phe Val Lys Val Gln Ala Val Tyr Ser
705 710 715 720
Arg Gln Asp Ser Phe Val Glu Leu Gly Ala Ile Ser Arg Asp Phe Ser
725 730 735
Asp Ser His Leu Tyr Asn Leu Ala Ile Pro Leu Gly Ile Lys Leu Glu
740 745 750
Lys Arg Phe Ala Glu Gln Tyr Tyr His Val Val Ala Met Tyr Ser Pro
755 760 765
Asp Val Cys Arg Ser Asn Pro Lys Cys Thr Thr Thr Leu Leu Ser Asn
770 775 780
Gln Gly Ser Trp Lys Thr Lys Gly Ser Ash Leu Ala Arg Gln Ala Gly
785 790 795 800
Ile Val Gln Ala Ser Gly Phe Arg Ser Leu Gly Ala Ala Ala Glu Leu
805 810 815
Phe Gly Asn Phe Gly Phe Glu Trp Arg Gly Ser Ser Arg Ser Tyr Ash
820 825 830
Val Asp Ala Gly Ser Lys Ile Lys Phe
835 840
(2)SEQ ID NO:9的信息:
(i)序列特征:
(A)长度:2787碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:9:
ATGAAGTCTT CTTTCCCCAA GTTTGTATTT TCTACATTTG CTATTTTCCC TTTGTCTATG 60
ATTGCTACCG AGACAGTTTT GGATTCAAGT GCGAGTTTCG ATGGGAATAA AAATGGTAAT 120
TTTTCAGTTC GTGAGAGTCA GGAAGATGCT GGAACTACCT ACCTATTTAA GGGAAATGTC 180
ACTCTAGAAA ATATTCCTGG AACAGGCACA GCAATCACAA AAAGCTGTTT TAACAACACT 240
AAGGGCGATT TGACTTTCAC AGGTAACGGG AACTCTCTAT TGTTCCAAAC GGTGGATGCA 300
GGGACTGTAG CAGGGGCTGC TGTTAACAGC AGCGTGGTAG ATAAATCTAC CACGTTTATA 360
GGGTTTTCTT CGCTATCTTT TATTGCGTCT CCTGGAAGTT CGATAACTAC CGGCAAAGGA 420
GCCGTTAGCT GCTCTACGGG TAGCTTGAAG TTTGACAAAA ATGTCAGTTT GCTCTTCAGC 480
AAAAACTTTT CAACGGATAA TGGCGGTGCT ATCACCGCAA AAACTCTTTC ATTAACAGGG 540
ACTACAATGT CAGCTCTGTT TTCTGAAAAT ACCTCCTCAA AGAAAGGCGG AGCCATTCAG 600
ACTTCCGATG CCCTTACCAT TACTGGAAAC CAAGGGGAAG TCTCTTTTTC TGACAATACT 660
TCTTCGGATT CTGGAGCTGC AATTTTTACA GAAGCCTCGG TGACTATTTC TAATAATGCT 720
AAAGTTTCCT TTATTGACAA TAAGGTCACA GGAGCGAGCT CCTCAACAAC GGGGGATATG 780
TCAGGAGGTG CTATCTGTGC TTATAAAACT AGTACAGATA CTAAGGTCAC CCTCACTGGA 840
AATCAGATGT TACTCTTCAG CAACAATACA TCGACAACAG CGGGAGGAGC TATCTATGTG 900
AAAAAGCTCG AACTGGCTTC CGGAGGACTT ACCCTATTCA GTAGAAATAG TGTCAATGGA 960
GGTACAGCTC CTAAAGGTGG AGCCATAGCT ATCGAAGATA GTGGGGAATT GAGTTTATCC 1020
GCCGATAGTG GTGACATTGT CTTTTTAGGG AATACAGTCA CTTCTACTAC TCCTGGGACG 1080
AATAGAAGTA GTATCGACTT AGGAACGAGT GCAAAGATGA CAGCTTTGCG TTCTGCTGCT 1140
GGTAGAGCCA TCTACTTCTA TGATCCCATA ACTACAGGAT CTTCCACAAC AGTTACAGAT 1200
GTCTTAAAAG TTAATGAGAC TCCGGCAGAT TCTGCACTAC AATATACAGG GAACATCATC 1260
TTCACAGGAG AAAAGTTATC AGAGACAGAG GCCGCAGATT CTAAAAATCT TACTTCGAAG 1320
CTACTACAGC CTGTAACTCT TTCAGGAGGT ACTCTATCTT TAAAACATGG AGTGACTCTG 1380
CAGACTCAGG CATTCACTCA ACAGGCAGAT TCTCGTCTCG AAATGGACGT AGGAACTACT 1440
CTAGAACCTG CTGATACTAG CACCATAAAC AATTTGGTCA TTAACATCAG TTCTATAGAC 1500
GGTGCAAAGA AGGCAAAAAT AGAAACCAAA GCTACGTCAA AAAATCTGAC TTTATCTGGA 1560
ACCATCACTT TATTGGACCC GACGGGCACG TTTTATGAAA ATCATAGTTT AAGAAATCCT 1620
CAGTCCTACG ACATCTTAGA GCTCAAAGCT TCTGGAACTG TAACAAGCAC CGCAGTGACT 1680
CCAGATCCTA TAATGGGTGA GAAATTCCAT TACGGCTATC AGGGAACTTG GGGCCCAATT 1740
GTTTGGGGGA CAGGGGCTTC TACGACTGCA ACCTTCAACT GGACTAAAAC TGGCTATATT 1800
CCTAATCCCG AGCGTATCGG CTCTTTAGTC CCTAATAGCT TATGGAATGC ATTTATAGAT 1860
ATTAGCTCTC TCCATTATCT TATGGAGACT GCAAACGAAG GGTTGCAGGG AGACCGTGCT 1920
TTTTGGTGTG CTGGATTATC TAACTTCTTC CATAAGGATA GTACAAAAAC ACGACGCGGG 1980
TTTCGCCATT TGAGTGGCGG TTATGTCATA GGAGGAAACC TACATACTTG TTCAGATAAG 2040
ATTCTTAGTG CTGCATTTTG TCAGCTCTTT GGAAGAGATA GAGACTACTT TGTAGCTAAG 2100
AATCAAGGTA CAGTCTACGG AGGAACTCTC TATTACCAGC ACAACGAAAC CTATATCTCT 2160
CTTCCTTGCA AACTACGGCC TTGTTCGTTG TCTTATGTTC CTACAGAGAT TCCTGTTCTC 2220
TTTTCAGGAA ACCTTAGCTA CACCCATACG GATAACGATC TGAAAACCAA GTATACAACA 2280
TATCCTACTG TTAAAGGAAG CTGGGGGAAT GATAGTTTCG CTTTAGAATT CGGTGGAAGA 2340
GCTCCGATTT GCTTAGATGA AAGTGCTCTA TTTGAGCAGT ACATGCCCTT CATGAAATTG 2400
CAGTTTGTCT ATGCACATCA GGAAGGTTTT AAAGAACAGG GAACAGAAGC TCGTGAATTT 2460
GGAAGTAGCC GTCTTGTGAA TCTTGCCTTA CCTATCGGGA TCCGATTTGA TAAGGAATCA 2520
GACTGCCAAG ATGCAACGTA CAATCTAACT CTTGGTTATA CTGTGGATCT TGTTCGTAGT 2580
AACCCCGACT GTACGACAAC ACTGCGAATT AGCGGTGATT CTTGGAAAAC CTTCGGTACG 2640
AATTTGGCAA GACAAGCTTT AGTCCTTCGT GCAGGGAACC ATTTTTGCTT TAACTCAAAT 2700
TTTGAAGCCT TTAGCCAATT TTCTTTTGAA TTGCGTGGGT CATCTCGCAA TTACAATGTA 2760
GACTTAGGAG CAAAATACCA ATTCTAA 2787
(2)SEQ ID NO:10的信息:
(i)序列特征:
(A)长度:928氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:10:
Met Lys Ser Ser Phe Pro Lys Phe Val Phe Ser Thr Phe Ala Ile Phe
1 5 10 15
Pro Leu Ser Met Ile Ala Thr Glu Thr Val Leu Asp Ser Ser Ala Ser
20 25 30
Phe Asp Gly Asn Lys Asn Gly Asn Phe Ser Val Arg Glu Ser Gln Glu
35 40 45
Asp Ala Gly Thr Thr Tyr Leu Phe Lys Gly Asn Val Thr Leu Glu Asn
50 55 60
Ile Pro Gly Thr Gly Thr Ala Ile Thr Lys Ser Cys Phe Asn Asn Thr
65 70 75 80
Lys Gly Asp Leu Thr Phe Thr Gly Asn Gly Asn Ser Leu Leu Phe Gln
85 90 95
Thr Val Asp Ala Gly Thr Val Ala Gly Ala Ala Val Asn Ser Ser Val
100 105 110
Val Asp Lys Ser Thr Thr Phe Ile Gly Phe Ser Ser Leu Ser Phe Ile
115 120 125
Ala Ser Pro Gly Ser Ser Ile Thr Thr Gly Lys Gly Ala Val Ser Cys
130 135 140
Ser Thr Gly Ser Leu Lys Phe Asp Lys Asn Val Ser Leu Leu Phe Ser
145 150 155 160
Lys Asn Phe Ser Thr Asp Asn Gly Gly Ala Ile Thr Ala Lys Thr Leu
165 170 175
Ser Leu Thr Gly Thr Thr Met Ser Ala Leu Phe Ser Glu Asn Thr Ser
180 185 190
Ser Lys Lys Gly Gly Ala Ile Gln Thr Ser Asp Ala Leu Thr Ile Thr
195 200 205
Gly Asn Gln Gly Glu Val Ser Phe Ser Asp Asn Thr Ser Ser Asp Ser
210 215 220
Gly Ala Ala Ile Phe Thr Glu Ala Ser Val Thr Ile Ser Asn Asn Ala
225 230 235 240
Lys Val Ser Phe Ile Asp Asn Lys Val Thr Gly Ala Ser Ser Ser Thr
245 250 255
Thr Gly Asp Met Ser Gly Gly Ala Ile Cys Ala Tyr Lys Thr Ser Thr
260 265 270
Asp Thr Lys Val Thr Leu Thr Gly Asn Gln Met Leu Leu Phe Ser Asn
275 280 285
Asn Thr Ser Thr Thr Ala Gly Gly Ala Ile Tyr Val Lys Lys Leu Glu
290 295 300
Leu Ala Ser Gly Gly Leu Thr Leu Phe Ser Arg Asn Ser Val Asn Gly
305 310 315 320
Gly Thr Ala Pro Lys Gly Gly Ala Ile Ala Ile Glu Asp Ser Gly Glu
325 330 335
Leu Ser Leu Ser Ala Asp Ser Gly Asp Ile Val Phe Leu Gly Asn Thr
340 345 350
Val Thr Ser Thr Thr Pro Gly Thr Asn Arg Ser Ser Ile Asp Leu Gly
355 360 365
Thr Ser Ala Lys Met Thr Ala Leu Arg Ser Ala Ala Gly Arg Ala Ile
370 375 380
Tyr Phe Tyr Asp Pro Ile Thr Thr Gly Ser Ser Thr Thr Val Thr Asp
385 390 395 400
Val Leu Lys Val Asn Glu Thr Pro Ala Asp Ser Ala Leu Gln Tyr Thr
405 410 415
Gly Asn Ile Ile Phe Thr Gly Glu Lys Leu Ser Glu Thr Glu Ala Ala
420 425 430
Asp Ser Lys Asn Leu Thr Ser Lys Leu Leu Gln Pro Val Thr Leu Ser
435 440 445
Gly Gly Thr Leu Ser Leu Lys His Gly Val Thr Leu Gln Thr Gln Ala
450 455 460
Phe Thr Gln Gln Ala Asp Ser Arg Leu Glu Met Asp Val Gly Thr Thr
465 470 475 480
Leu Glu Pro Ala Asp Thr Ser Thr Ile Asn Asn Leu Val Ile Asn Ile
485 490 495
Ser Ser Ile Asp Gly Ala Lys Lys Ala Lys Ile Glu Thr Lys Ala Thr
500 505 510
Ser Lys Asn Leu Thr Leu Ser Gly Thr Ile Thr Leu Leu Asp Pro Thr
515 520 525
Gly Thr Phe Tyr Glu Asn His Ser Leu Arg Asn Pro Gln Ser Tyr Asp
530 535 540
Ile Leu Glu Leu Lys Ala Ser Gly Thr Val Thr Ser Thr Ala Val Thr
545 550 555 560
Pro Asp Pro Ile Met Gly Glu Lys Phe His Tyr Gly Tyr Gln Gly Thr
565 570 575
Trp Gly Pro Ile Val Trp Gly Thr Gly Ala Ser Thr Thr Ala Thr Phe
580 585 590
Asn Trp Thr Lys Thr Gly Tyr Ile Pro Asn Pro Glu Arg Ile Gly Ser
595 600 605
Leu Val Pro Asn Ser Leu Trp Asn Ala Phe Ile Asp Ile Ser Ser Leu
610 615 620
His Tyr Leu Met Glu Thr Ala Asn Glu Gly Leu Gln Gly Asp Arg Ala
625 630 635 640
Phe Trp Cys Ala Gly Leu Ser Asn Phe Phe His Lys Asp Ser Thr Lys
645 650 655
Thr Arg Arg Gly Phe Arg His Leu Ser Gly Gly Tyr Val Ile Gly Gly
660 665 670
Asn Leu His Thr Cys Ser Asp Lys Ile Leu Ser Ala Ala Phe Cys Gln
675 680 685
Leu Phe Gly Arg Asp Arg Asp Tyr Phe Val Ala Lys Asn Gln Gly Thr
690 695 700
Val Tyr Gly Gly Thr Leu Tyr Tyr Gln His Asn Glu Thr Tyr Ile Ser
705 710 715 720
Leu Pro Cys Lys Leu Arg Pro Cys Ser Leu Ser Tyr Val Pro Thr Glu
725 730 735
Ile Pro Val Leu Phe Ser Gly Asn Leu Ser Tyr Thr His Thr Asp Asn
740 745 750
Asp Leu Lys Thr Lys Tyr Thr Thr Tyr Pro Thr Val Lys Gly Ser Trp
755 760 765
Gly Asn Asp Ser Phe Ala Leu Glu Phe Gly Gly Arg Ala Pro Ile Cys
770 775 780
Leu Asp Glu Ser Ala Leu Phe Glu Gln Tyr Met Pro Phe Met Lys Leu
785 790 795 800
Gln Phe Val Tyr Ala His Gln Glu Gly Phe Lys Glu Gln Gly Thr Glu
805 810 815
Ala Arg Glu Phe Gly Ser Ser Arg Leu Val Asn Leu Ala Leu Pro Ile
820 825 830
Gly Ile Arg Phe Asp Lys Glu Ser Asp Cys Gln Asp Ala Thr Tyr Asn
835 840 845
Leu Thr Leu Gly Tyr Thr Val Asp Leu Val Arg Ser Asn Pro Asp Cys
850 855 860
Thr Thr Thr Leu Arg Ile Ser Gly Asp Ser Trp Lys Thr Phe Gly Thr
865 870 875 880
Asn Leu Ala Arg Gln Ala Leu Val Leu Arg Ala Gly Asn His Phe Cys
885 890 895
Phe Asn Ser Asn Phe Glu Ala Phe Ser Gln Phe Ser Phe Glu Leu Arg
900 905 910
Gly Ser Ser Arg Asn Tyr Asn Val Asp Leu Gly Ala Lys Tyr Gln Phe
915 920 925
(2)SEQ ID NO:11的信息:
(i)序列特征:
(A)长度:2757碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:11:
ATGAGATCGT CTTTTTCCTT GTTATTAATA TCTTCATCTC TAGCCTTTCC TCTCTTAATG 60
AGTGTTTCTG CAGATGCTGC CGATCTCACA TTAGGGAGTC GTGACAGTTA TAATGGTGAT 120
ACAAGCACCA CAGAATTTAC TCCTAAAGCG GCAACTTCTG ATGCTAGTGG CACGACCTAT 180
ATTCTCGATG GGGATGTCTC GATAAGCCAA GCAGGGAAAC AAACGAGCTT AACCACAAGT 240
TGTTTTTCTA ACACTGCAGG AAATCTTACC TTCTTAGGGA ACGGATTTTC TCTTCATTTT 300
GACAATATTA TTTCGTCTAC TGTTGCAGGT GTTGTTGTTA GCAATACAGC AGCTTCTGGG 360
ATTACGAAAT TCTCAGGATT TTCAACTCTT CGGATGCTTG CAGCTCCTAG GACCACAGGT 420
AAAGGAGCCA TTAAAATTAC CGATGGTCTG GTGTTTGAGA GTATAGGGAA TCTTGACCAA 480
AATGAAAATG CCTCTAGTGA AAATGGGGGA GCCATCAATA CGAAGACTTT GTCTTTGACT 540
GGGAGTACGC GGTTTGTAGC GTTCCTTGGC AATAGCTCGT CGCAACAAGG GGGAGCGATC 600
TATGCTTCTG GTGACTCTGT GATTTCTGAG AATGCAGGAA TCTTGAGCTT CGGAAACAAC 660
AGTGCGACAA CATCAGGAGG CGCGATCTCT GCTGAAGGGA ACCTTGTGAT CTCCAATAAC 720
CAAAATATCT TTTTCGATGG CTGCAAAGCA ACTACAAATG GCGGAGCTAT TGATTGTAAC 780
AAAGCAGGGG CGAACCCAGA CCCTATCTTG ACTCTTTCAG GAAATGAGAG CCTGCATTTT 840
CTGAATAACA CAGCAGGAAA TAGTGGAGGT GCGATTTATA CCAAAAAATT GGTGTTATCC 900
TCAGGACGAG GAGGAGTGTT ATTTTCTAAC AACAAAGCTG CGAATGCTAC TCCTAAAGGA 960
GGGGCAATTG CGATTCTAGA TTCTGGAGAG ATTAGCATTT CTGCAGATCT CGGCAATATC 1020
ATTTTCGAGG GCAATACTAC GAGCACTACA GGAAGTCCTG CGAGTGTGAC CAGAAATGCT 1080
ATAGATCTTG CATCGAATGC AAAATTTTTA AATCTCCGAG CGACTCGGGG AAATAAAGTT 1140
ATTTTCTATG ATCCTATCAC GAGCTCAGGA GCTACTGATA AGCTCTCTTT GAATAAAGCT 1200
GACGCAGGAT CTGGAAATAC CTATGAAGGC TACATCGTTT TCTCTGGAGA GAAACTCTCA 1260
GAAGAGGAAC TTAAGAAACC TGACAATCTG AAGTCTACAT TTACACAGGC TGTAGAGCTT 1320
GCTGCAGGTG CCTTAGTATT GAAAGATGGA GTGACTGTAG TTGCAAATAC TATAACGCAG 1380
GTCGAGGGAT CGAAAGTCGT TATGGATGGA GGGACTACTT TTGAGGCAAG CGCTGAGGGG 1440
GTCACTCTCA ATGGCCTAGC CATTAATATA GATTCCTTAG ATGGGACAAA TAAAGCTATC 1500
ATTAAGGCGA CGGCAGCAAG TAAGGATGTT GCCTTATCAG GGCCTATCAT GCTTGTAGAT 1560
GCTCAGGGGA ACTATTATGA GCATCATAAT CTCAGTCAAC AGCAGGTCTT TCCTTTAATA 1620
GAGCTTTCTG CACAAGGAAC GATGACTACT ACAGATATCC CCGATACCCC AATTCTAAAT 1680
ACTACGAATC ACTATGGGTA TCAAGGAACT GGAATAATTG TTTGGGTCGA CGATGCAACT 1740
GCAAAAACAA AAAATGCTAC CTTAACTTGG ACTAAAACAG GATACAAGCC GAATCCAGAA 1800
CGTCAGGGAC CTTTGGTTCC TAATAGCCTG TGGGGTTCTT TTGTCGATGT CCGCTCCATT 1860
CAGAGCCTCA TGGACCGGAG CACAAGTTCG TTATCTTCGT CAACAAATTT GTGGGTATCA 1920
GGAATCGCGG ACTTTTTGCA TGAAGATCAG AAAGGAAACC AACGTAGTTA TCGTCATTCT 1980
AGCGCGGGTT ATGCATTAGG AGGAGGATTC TTCACGGCTT CTGAAAATTT CTTTAATTTT 2040
GCTTTTTGTC AGCTTTTTGG CTACGACAAG GACCATCTTG TGGCTAAGAA CCATACCCAT 2100
GTATATGCAG GGGCAATGAG TTACCGACAC CTCGGAGAGT CTAAGACCCT CGCTAAGATT 2160
TTGTCAGGAA ATTCTGACTC CCTACCTTTT GTCTTCAATG CTCGGTTTGC TTATGGCCAT 2220
ACCGACAATA ACATGACCAC AAAGTACACT GGCTATTCTC CTGTTAAGGG AAGCTGGGGA 2280
AATGATGCCT TCGGTATAGA ATGTGGAGGA GCTATCCCGG TAGTTGCTTC AGGACGTCGG 2340
TCTTGGGTGG ATACCCACAC GCCATTTCTA AACCTAGAGA TGATCTATGC ACATCAGAAT 2400
GACTTTAAGG AAAACGGCAC AGAAGGCCGT TCTTTCCAAA GTGAAGACCT CTTCAATCTA 2460
GCGGTTCCTG TAGGGATAAA ATTTGAGAAA TTCTCCGATA AGTCTACGTA TGATCTCTCC 2520
ATAGCTTACG TTCCCGATGT GATTCGTAAT GATCCAGGCT GCACGACAAC TCTTATGGTT 2580
TCTGGGGATT CTTGGTCGAC ATGTGGTACA AGCTTGTCTA GACAAGCTCT TCTTGTACGT 2640
GCTGGAAATC ATCATGCCTT TGCTTCAAAC TTTGAAGTTT TCAGTCAGTT TGAAGTCGAG 2700
TTGCGAGGTT CTTCTCGTAG CTATGCTATC GATCTTGGAG GAAGATTCGG ATTTTAA 2757
(2)SEQ ID NO:12的信息:
(i)序列特征:
(A)长度:918氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:12:
Met Arg Ser Ser Phe Ser Leu Leu Leu Ile Ser Ser Ser Leu Ala Phe
1 5 10 15
Pro Leu Leu Met Ser Val Ser Ala Asp Ala Ala Asp Leu Thr Leu Gly
20 25 30
Ser Arg Asp Ser Tyr Asn Gly Asp Thr Ser Thr Thr Glu Phe Thr Pro
35 40 45
Lys Ala Ala Thr Ser Asp Ala Ser Gly Thr Thr Tyr Ile Leu Asp Gly
50 55 60
Asp Val Ser Ile Ser Gln Ala Gly Lys Gln Thr Ser Leu Thr Thr Ser
65 70 75 80
Cys Phe Ser Asn Thr Ala Gly Asn Leu Thr Phe Leu Gly Asn Gly Phe
85 90 95
Ser Leu His Phe Asp Asn Ile Ile Ser Ser Thr Val Ala Gly Val Val
100 105 110
Val Ser Asn Thr Ala Ala Ser Gly Ile Thr Lys Phe Ser Gly Phe Ser
115 120 125
Thr Leu Arg Met Leu Ala Ala Pro Arg Thr Thr Gly Lys Gly Ala Ile
130 135 140
Lys Ile Thr Asp Gly Leu Val Phe Glu Ser Ile Gly Asn Leu Asp Gln
145 150 155 160
Asn Glu Asn Ala Ser Ser Glu Asn Gly Gly Ala Ile Asn Thr Lys Thr
165 170 175
Leu Ser Leu Thr Gly Ser Thr Arg Phe Val Ala Phe Leu Gly Asn Ser
180 185 190
Ser Ser Gln Gln Gly Gly Ala Ile Tyr Ala Ser Gly Asp Ser Val Ile
195 200 205
Ser Glu Asn Ala Gly Ile Leu Ser Phe Gly Asn Asn Ser Ala Thr Thr
210 215 220
Ser Gly Gly Ala Ile Ser Ala Glu Gly Asn Leu Val Ile Ser Asn Asn
225 230 235 240
Gln Asn Ile Phe Phe Asp Gly Cys Lys Ala Thr Thr Asn Gly Gly Ala
245 250 255
Ile Asp Cys Asn Lys Ala Gly Ala Asn Pro Asp Pro Ile Leu Thr Leu
260 265 270
Ser Gly Asn Glu Ser Leu His Phe Leu Asn Asn Thr Ala Gly Asn Ser
275 280 285
Gly Gly Ala Ile Tyr Thr Lys Lys Leu Val Leu Ser Ser Gly Arg Gly
290 295 300
Gly Val Leu Phe Ser Asn Asn Lys Ala Ala Asn Ala Thr Pro Lys Gly
305 310 315 320
Gly Ala Ile Ala Ile Leu Asp Ser Gly Glu Ile Ser Ile Ser Ala Asp
325 330 335
Leu Gly Asn Ile Ile Phe Glu Gly Asn Thr Thr Ser Thr Thr Gly Ser
340 345 350
Pro Ala Ser Val Thr Arg Asn Ala Ile Asp Leu Ala Ser Asn Ala Lys
355 360 365
Phe Leu Asn Leu Arg Ala Thr Arg Gly Asn Lys Val Ile Phe Tyr Asp
370 375 380
Pro Ile Thr Ser Ser Gly Ala Thr Asp Lys Leu Ser Leu Asn Lys Ala
385 390 395 400
Asp Ala Gly Ser Gly Asn Thr Tyr Glu Gly Tyr Ile Val Phe Ser Gly
405 410 415
Glu Lys Leu Ser Glu Glu Glu Leu Lys Lys Pro Asp Asn Leu Lys Ser
420 425 430
Thr Phe Thr Gln Ala Val Glu Leu Ala Ala Gly Ala Leu Val Leu Lys
435 440 445
Asp Gly Val Thr Val Val Ala Asn Thr Ile Thr Gln Val Glu Gly Ser
450 455 460
Lys Val Val Met Asp Gly Gly Thr Thr Phe Glu Ala Ser Ala Glu Gly
465 470 475 480
Val Thr Leu Asn Gly Leu Ala Ile Asn Ile Asp Ser Leu Asp Gly Thr
485 490 495
Asn Lys Ala Ile Ile Lys Ala Thr Ala Ala Ser Lys Asp Val Ala Leu
500 505 510
Ser Gly Pro Ile Met Leu Val Asp Ala Gln Gly Asn Tyr Tyr Glu His
515 520 525
His Asn Leu Ser Gln Gln Gln Val Phe Pro Leu Ile Glu Leu Ser Ala
530 535 540
Gln Gly Thr Met Thr Thr Thr Asp Ile Pro Asp Thr Pro Ile Leu Asn
545 550 555 560
Thr Thr Asn His Tyr Gly Tyr Gln Gly Thr Gly Ile Ile Val Trp Val
565 570 575
Asp Asp Ala Thr Ala Lys Thr Lys Asn Ala Thr Leu Thr Trp Thr Lys
580 585 590
Thr Gly Tyr Lys Pro Asn Pro Glu Arg Gln Gly Pro Leu Val Pro Asn
595 600 605
Ser Leu Trp Gly Ser Phe Val Asp Val Arg Ser Ile Gln Ser Leu Met
610 615 620
Asp Arg Ser Thr Ser Ser Leu Ser Ser Ser Thr Asn Leu Trp Val Ser
625 630 635 640
Gly Ile Ala Asp Phe Leu His Glu Asp Gln Lys Gly Asn Gln Arg Ser
645 650 655
Tyr Arg His Ser Ser Ala Gly Tyr Ala Leu Gly Gly Gly Phe Phe Thr
660 665 670
Ala Ser Glu Asn Phe Phe Asn Phe Ala Phe Cys Gln Leu Phe Gly Tyr
675 680 685
Asp Lys Asp His Leu Val Ala Lys Asn His Thr His Val Tyr Ala Gly
690 695 700
Ala Met Ser Tyr Arg His Leu Gly Glu Ser Lys Thr Leu Ala Lys Ile
705 710 715 720
Leu Ser Gly Asn Ser Asp Ser Leu Pro Phe Val Phe Asn Ala Arg Phe
725 730 735
Ala Tyr Gly His Thr Asp Asn Asn Met Thr Thr Lys Tyr Thr Gly Tyr
740 745 750
Ser Pro Val Lys Gly Ser Trp Gly Asn Asp Ala Phe Gly Ile Glu Cys
755 760 765
Gly Gly Ala Ile Pro Val Val Ala Ser Gly Arg Arg Ser Trp Val Asp
770 775 780
Thr His Thr Pro Phe Leu Asn Leu Glu Met Ile Tyr Ala His Gln Asn
785 790 795 800
Asp Phe Lys Glu Asn Gly Thr Glu Gly Arg Ser Phe Gln Ser Glu Asp
805 810 815
Leu Phe Asn Leu Ala Val Pro Val Gly Ile Lys Phe Glu Lys Phe Ser
820 825 830
Asp Lys Ser Thr Tyr Asp Leu Ser Ile Ala Tyr Val Pro Asp Val Ile
835 840 845
Arg Asn Asp Pro Gly Cys Thr Thr Thr Leu Met Val Ser Gly Asp Ser
850 855 860
Trp Ser Thr Cys Gly Thr Ser Leu Ser Arg Gln Ala Leu Leu Val Arg
865 870 875 880
Ala Gly Asn His His Ala Phe Ala Ser Asn Phe Glu Val Phe Ser Gln
885 890 895
Phe Glu Val Glu Leu Arg Gly Ser Ser Arg Ser Tyr Ala Ile Asp Leu
900 905 910
Gly Gly Arg Phe Gly Phe
915
(2)SEQ ID NO:13的信息:
(i)序列特征:
(A)长度:2787碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:13:
ATGAAATCCT CTCTTCATTG GTTTGTAATC TCGTCATCTT TAGCACTTCC CTTGTCACTA 60
AATTTCTCTG CGTTTGCTGC TGTTGTTGAA ATCAATCTAG GACCTACCAA TAGCTTCTCT 120
GGACCAGGAA CCTACACTCC TCCAGCCCAA ACAACAAATG CAGATGGAAC TATCTATAAT 180
CTAACAGGGG ATGTCTCAAT CACCAATGCA GGATCTCCGA CAGCTCTAAC CGCTTCCTGC 240
TTTAAAGAAA CTACTGGGAA TCTTTCTTTC CAAGGCCACG GCTACCAATT TCTCCTACAA 300
AATATCGATG CGGGAGCGAA CTGTACCTTT ACCAATACAG CTGCAAATAA GCTTCTCTCC 360
TTTTCAGGAT TCTCCTATTT GTCACTAATA CAAACCACGA ATGCTACCAC AGGAACAGGA 420
GCCATCAAGT CCACAGGAGC TTGTTCTATT CAGTCGAACT ATAGTTGCTA CTTTGGCCAA 480
AACTTTTCTA ATGACAATGG AGGCGCCCTC CAAGGCAGCT CTATCAGTCT ATCGCTAAAC 540
CCCAACCTAA CGTTTGCCAA AAACAAAGCA ACGCAAAAAG GGGGTGCCCT CTATTCCACG 600
GGAGGGATTA CAATTAACAA TACGTTAAAC TCAGCATCAT TTTCTGAAAA TACCGCGGCG 660
AACAATGGCG GAGCCATTTA CACGGAAGCT AGCAGTTTTA TTAGCAGCAA CAAAGCAATT 720
AGCTTTATAA ACAATAGTGT GACCGCAACC TCAGCTACAG GGGGAGCCAT TTACTGTAGT 780
AGTACATCAG CCCCCAAACC AGTCTTAACT CTATCAGACA ACGGGGAACT GAACTTTATA 840
GGAAATACAG CAATTACTAG TGGTGGGGCG ATTTATACTG ACAATCTAGT TCTTTCTTCT 900
GGAGGACCTA CGCTTTTTAA AAACAACTCT GCTATAGATA CTGCAGCTCC CTTAGGAGGA 960
GCAATTGCGA TTGCTGACTC TGGATCTTTG AGTCTTTCGG CTCTTGGTGG AGACATCACT 1020
TTTGAAGGAA ACACAGTAGT CAAAGGAGCT TCTTCGAGTC AGACCACTAC CAGAAATTCT 1080
ATTAACATCG GAAACACCAA TGCTAAGATT GTACAGCTGC GAGCCTCTCA AGGCAATACT 1140
ATCTACTTCT ATGATCCTAT AACAACTAAC CATACTGCAG CTCTCTCAGA TGCTCTAAAC 1200
TTAAATGGTC CTGACCTTGC AGGGAATCCT GCATATCAAG GAACCATCGT ATTTTCTGGA 1260
GAGAAGCTCT CGGAAGCAGA AGCTGCAGAA GCTGATAATC TCAAATCTAC AATTCAGCAA 1320
CCTCTAACTC TTGCGGGAGG GCAACTCTCT CTTAAATCAG GAGTCACTCT AGTTGCTAAG 1380
TCCTTTTCGC AATCTCCGGG CTCTACCCTC CTCATGGATG CAGGGACCAC ATTAGAAACC 1440
GCTGATGGGA TCACTATCAA TAATCTTGTT CTCAATGTAG ATTCCTTAAA AGAGACCAAG 1500
AAGGCTACGC TAAAAGCAAC ACAAGCAAGT CAGACAGTCA CTTTATCTGG ATCGCTCTCT 1560
CTTGTAGATC CTTCTGGAAA TGTCTACGAA GATGTCTCTT GGAATAACCC TCAAGTCTTT 1620
TCTTGTCTCA CTCTTACTGC TGACGACCCC GCGAATATTC ACATCACAGA CTTAGCTGCT 1680
GATCCCCTAG AAAAAAATCC TATCCATTGG GGATACCAAG GGAATTGGGC ATTATCTTGG 1740
CAAGAGGATA CTGCGACTAA ATCCAAAGCA GCGACTCTTA CCTGGACAAA AACAGGATAC 1800
AATCCGAATC CTGAGCGTCG TGGAACCTTA GTTGCTAACA CGCTATGGGG ATCCTTTGTT 1860
GATGTGCGCT CCATACAACA GCTTGTAGCC ACTAAAGTAC GCCAATCTCA AGAAACTCGC 1920
GGCATCTGGT GTGAAGGGAT CTCGAACTTC TTCCATAAAG ATAGCACGAA GATAAATAAA 1980
GGTTTTCGCC ACATAAGTGC AGGTTATGTT GTAGGAGCGA CTACAACATT AGCTTCTGAT 2040
AATCTTATCA CTGCAGCCTT CTGCCAATTA TTCGGGAAAG ATAGAGATCA CTTTATAAAT 2100
AAAAATAGAG CTTCTGCCTA TGCAGCTTCT CTCCATCTCC AGCATCTAGC GACCTTGTCT 2160
TCTCCAAGCT TGTTACGCTA CCTTCCTGGA TCTGAAAGTG AGCAGCCTGT CCTCTTTGAT 2220
GCTCAGATCA GCTATATCTA TAGTAAAAAT ACTATGAAAA CCTATTACAC CCAAGCACCA 2280
AAGGGAGAGA GCTCGTGGTA TAATGACGGT TGCGCTCTGG AACTTGCGAG CTCCCTACCA 2340
CACACTGCTT TAAGCCATGA GGGTCTCTTC CACGCGTATT TTCCTTTCAT CAAAGTAGAA 2400
GCTTCGTACA TACACCAAGA TAGCTTCAAA GAACGTAATA CTACCTTGGT ACGATCTTTC 2460
GATAGCGGTG ATTTAATTAA CGTCTCTGTG CCTATTGGAA TTACCTTCGA GAGATTCTCG 2520
AGAAACGAGC GTGCGTCTTA CGAAGCTACT GTCATCTACG TTGCCGATGT CTATCGTAAG 2580
AATCCTGACT GCACGACAGC TCTCCTAATC AACAATACCT CGTGGAAAAC TACAGGAACG 2640
AATCTCTCAA GACAAGCTGG TATCGGAAGA GCAGGGATCT TTTATGCCTT CTCTCCAAAT 2700
CTTGAGGTCA CAAGTAACCT ATCTATGGAA ATTCGTGGAT CTTCACGCAG CTACAATGCA 2760
GATCTTGGAG GTAAGTTCCA GTTCTAA 2787
(2)SEQ ID NO:14的信息:
(i)序列特征:
(A)长度:928氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:14:
Met Lys Ser Ser Leu His Trp Phe Val Ile Ser Ser Ser Leu Ala Leu
1 5 10 15
Pro Leu Ser Leu Asn Phe Ser Ala Phe Ala Ala Val Val Glu Ile Asn
20 25 30
Leu Gly Pro Thr Asn Ser Phe Ser Gly Pro Gly Thr Tyr Thr Pro Pro
35 40 45
Ala Gln Thr Thr Asn Ala Asp Gly Thr Ile Tyr Asn Leu Thr Gly Asp
50 55 60
Val Ser Ile Thr Asn Ala Gly Ser Pro Thr Ala Leu Thr Ala Ser Cys
65 70 75 80
Phe Lys Glu Thr Thr Gly Asn Leu Ser Phe Gln Gly His Gly Tyr Gln
85 90 95
Phe Leu Leu Gln Asn Ile Asp Ala Gly Ala Asn Cys Thr Phe Thr Asn
100 105 110
Thr Ala Ala Asn Lys Leu Leu Ser Phe Ser Gly Phe Ser Tyr Leu Ser
115 120 125
Leu Ile Gln Thr Thr Asn Ala Thr Thr Gly Thr Gly Ala Ile Lys Ser
130 135 140
Thr Gly Ala Cys Ser Ile Gln Ser Asn Tyr Ser Cys Tyr Phe Gly Gln
145 150 155 160
Asn Phe Ser Asn Asp Asn Gly Gly Ala Leu Gln Gly Ser Ser Ile Ser
165 170 175
Leu Ser Leu Asn Pro Asn Leu Thr Phe Ala Lys Asn Lys Ala Thr Gln
180 185 190
Lys Gly Gly Ala Leu Tyr Ser Thr Gly Gly Ile Thr Ile Asn Asn Thr
195 200 205
Leu Asn Ser Ala Ser Phe Ser Glu Asn Thr Ala Ala Asn Asn Gly Gly
210 215 220
Ala Ile Tyr Thr Glu Ala Ser Ser Phe Ile Ser Ser Asn Lys Ala Ile
225 230 235 240
Ser Phe Ile Asn Asn Ser Val Thr Ala Thr Ser Ala Thr Gly Gly Ala
245 250 255
Ile Tyr Cys Ser Ser Thr Ser Ala Pro Lys Pro Val Leu Thr Leu Ser
260 265 270
Asp Asn Gly Glu Leu Asn Phe Ile Gly Asn Thr Ala Ile Thr Ser Gly
275 280 285
Gly Ala Ile Tyr Thr Asp Asn Leu Val Leu Ser Ser Gly Gly Pro Thr
290 295 300
Leu Phe Lys Asn Asn Ser Ala Ile Asp Thr Ala Ala Pro Leu Gly Gly
305 310 315 320
Ala Ile Ala Ile Ala Asp Ser Gly Ser Leu Ser Leu Ser Ala Leu Gly
325 330 335
Gly Asp Ile Thr Phe Glu Gly Asn Thr Val Val Lys Gly Ala Ser Ser
340 345 350
Ser Gln Thr Thr Thr Arg Asn Ser Ile Asn Ile Gly Asn Thr Asn Ala
355 360 365
Lys Ile Val Gln Leu Arg Ala Ser Gln Gly Asn Thr Ile Tyr Phe Tyr
370 375 380
Asp Pro Ile Thr Thr Asn His Thr Ala Ala Leu Ser Asp Ala Leu Asn
385 390 395 400
Leu Asn Gly Pro Asp Leu Ala Gly Asn Pro Ala Tyr Gln Gly Thr Ile
405 410 415
Val Phe Ser Gly Glu Lys Leu Ser Glu Ala Glu Ala Ala Glu Ala Asp
420 425 430
Asn Leu Lys Ser Thr Ile Gln Gln Pro Leu Thr Leu Ala Gly Gly Gln
435 440 445
Leu Ser Leu Lys Ser Gly Val Thr Leu Val Ala Lys Ser Phe Ser Gln
450 455 460
Ser Pro Gly Ser Thr Leu Leu Met Asp Ala Gly Thr Thr Leu Glu Thr
465 470 475 480
Ala Asp Gly Ile Thr Ile Asn Asn Leu Val Leu Asn Val Asp Ser Leu
485 490 495
Lys Glu Thr Lys Lys Ala Thr Leu Lys Ala Thr Gln Ala Ser Gln Thr
500 505 510
Val Thr Leu Ser Gly Ser Leu Ser Leu Val Asp Pro Ser Gly Asn Val
515 520 525
Tyr Glu Asp Val Ser Trp Asn Asn Pro Gln Val Phe Ser Cys Leu Thr
530 535 540
Leu Thr Ala Asp Asp Pro Ala Asn Ile His Ile Thr Asp Leu Ala Ala
545 550 555 560
Asp Pro Leu Glu Lys Asn Pro Ile His Trp Gly Tyr Gln Gly Asn Trp
565 570 575
Ala Leu Ser Trp Gln Glu Asp Thr Ala Thr Lys Ser Lys Ala Ala Thr
580 585 590
Leu Thr Trp Thr Lys Thr Gly Tyr Asn Pro Asn Pro Glu Arg Arg Gly
595 600 605
Thr Leu Val Ala Asn Thr Leu Trp Gly Ser Phe Val Asp Val Arg Ser
610 615 620
Ile Gln Gln Leu Val Ala Thr Lys Val Arg Gln Ser Gln Glu Thr Arg
625 630 635 640
Gly Ile Trp Cys Glu Gly Ile Ser Asn Phe Phe His Lys Asp Ser Thr
645 650 655
Lys Ile Asn Lys Gly Phe Arg His Ile Ser Ala Gly Tyr Val Val Gly
660 665 670
Ala Thr Thr Thr Leu Ala Ser Asp Asn Leu Ile Thr Ala Ala Phe Cys
675 680 685
Gln Leu Phe Gly Lys Asp Arg Asp His Phe Ile Asn Lys Asn Arg Ala
690 695 700
Ser Ala Tyr Ala Ala Ser Leu His Leu Gln His Leu Ala Thr Leu Ser
705 710 715 720
Ser Pro Ser Leu Leu Arg Tyr Leu Pro Gly Ser Glu Ser Glu Gln Pro
725 730 735
Val Leu Phe Asp Ala Gln Ile Ser Tyr Ile Tyr Ser Lys Asn Thr Met
740 745 750
Lys Thr Tyr Tyr Thr Gln Ala Pro Lys Gly Glu Ser Ser Trp Tyr Asn
755 760 765
Asp Gly Cys Ala Leu Glu Leu Ala Ser Ser Leu Pro His Thr Ala Leu
770 775 780
Ser His Glu Gly Leu Phe His Ala Tyr Phe Pro Phe Ile Lys Val Glu
785 790 795 800
Ala Ser Tyr Ile His Gln Asp Ser Phe Lys Glu Arg Asn Thr Thr Leu
805 810 815
Val Arg Ser Phe Asp Ser Gly Asp Leu Ile Asn Val Ser Val Pro Ile
820 825 830
Gly Ile Thr Phe Glu Arg Phe Ser Arg Asn Glu Arg Ala Ser Tyr Glu
835 840 845
Ala Thr Val Ile Tyr Val Ala Asp Val Tyr Arg Lys Asn Pro Asp Cys
850 855 860
Thr Thr Ala Leu Leu Ile Asn Asn Thr Ser Trp Lys Thr Thr Gly Thr
865 870 875 880
Asn Leu Ser Arg Gln Ala Gly Ile Gly Arg Ala Gly Ile Phe Tyr Ala
885 890 895
Phe Ser Pro Asn Leu Glu Val Thr Ser Asn Leu Ser Met Glu Ile Arg
900 905 910
Gly Ser Ser Arg Ser Tyr Asn Ala Asp Leu Gly Gly Lys Phe Gln Phe
915 920 925
(2)SEQ ID NO:15的信息:
(i)序列特征:
(A)长度:2793碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:15:
ATGAAAATAC CCTTGCACAA ACTCCTGATC TCTTCGACTC TTGTCACTCC CATTCTATTG 60
AGCATTGCAA CTTACGGAGC AGATGCTTCT TTATCCCCTA CAGATAGCTT TGATGGAGCG 120
GGCGGCTCTA CATTTACTCC AAAATCTACA GCAGATGCCA ATGGAACGAA CTATGTCTTA 180
TCAGGAAATG TCTATATAAA CGATGCTGGG AAAGGCACAG CATTAACAGG CTGCTGCTTT 240
ACAGAAACTA CGGGTGATCT GACATTTACT GGAAAGGGAT ACTCATTTTC ATTCAACACG 300
GTAGATGCGG GTTCGAATGC AGGAGCTGCG GCAAGCACAA CTGCTGATAA AGCCCTAACA 360
TTCACAGGAT TTTCTAACCT TTCCTTCATT GCAGCTCCTG GAACTACAGT TGCTTCAGGA 420
AAAAGTACTT TAAGTTCTGC AGGAGCCTTA AATCTTACCG ATAATGGAAC GATTCTCTTT 480
AGCCAAAACG TCTCCAATGA AGCTAATAAC AATGGCGGAG CGATCACCAC AAAAACTCTT 540
TCTATTTCTG GGAATACCTC TTCTATAACC TTCACTAGTA ATAGCGCAAA AAAATTAGGT 600
GGAGCGATCT ATAGCTCTGC GGCTGCAAGT ATTTCAGGAA ACACCGGCCA GTTAGTCTTT 660
ATGAATAATA AAGGAGAAAC TGGGGGCGGG GCTCTGGGCT TTGAAGCCAG CTCCTCGATT 720
ACTCAAAATA GCTCCCTTTT CTTCTCTGGA AACACTGCAA CAGATGCTGC AGGCAAGGGC 780
GGGGCCATTT ATTGTGAAAA AACAGGAGAG ACTCCTACTC TTACTATCTC TGGAAATAAA 840
AGTCTGACCT TCGCCGAGAA CTCTTCAGTA ACTCAAGGCG GAGCAATCTG TGCCCATGGT 900
CTAGATCTTT CCGCTGCTGG CCCTACCCTA TTTTCAAATA ATAGATGCGG GAACACAGCT 960
GCAGGCAAGG GCGGCGCTAT TGCAATTGCC GACTCTGGAT CTTTAAGTCT CTCTGCAAAT 1020
CAAGGAGACA TCACGTTCCT TGGCAACACT CTAACCTCAA CCTCCGCGCC AACATCGACA 1080
CGGAATGCTA TCTACCTGGG ATCGTCAGCA AAAATTACGA ACTTAAGGGC AGCCCAAGGC 1140
CAATCTATCT ATTTCTATGA TCCGATTGCA TCTAACACCA CAGGAGCTTC AGACGTTCTG 1200
ACCATCAACC AACCGGATAG CAACTCGCCT TTAGATTATT CAGGAACGAT TGTATTTTCT 1260
GGGGAAAAGC TCTCTGCAGA TGAAGCGAAA GCTGCTGATA ACTTCACATC TATATTAAAG 1320
CAACCATTGG CTCTAGCCTC TGGAACCTTA GCACTCAAAG GAAATGTCGA GTTAGATGTC 1380
AATGGTTTCA CACAGACTGA AGGCTCTACA CTCCTCATGC AACCAGGAAC AAAGCTCAAA 1440
GCAGATACTG AAGCTATCAG TCTTACCAAA CTTGTCGTTG ATCTTTCTGC CTTAGAGGGA 1500
AATAAGAGTG TGTCCATTGA AACAGCAGGA GCCAACAAAA CTATAACTCT AACCTCTCCT 1560
CTTGTTTTCC AAGATAGTAG CGGCAATTTT TATGAAAGCC ATACGATAAA CCAAGCCTTC 1620
ACGCAGCCTT TGGTGGTATT CACTGCTGCT ACTGCTGCTA GCGATATTTA TATCGATGCG 1680
CTTCTCACTT CTCCAGTACA AACTCCAGAA CCTCATTACG GGTATCAGGG ACATTGGGAA 1740
GCCACTTGGG CAGACACATC AACTGCAAAA TCAGGAACTA TGACTTGGGT AACTACGGGC 1800
TACAACCCTA ATCCTGAGCG TAGAGCTTCC GTAGTTCCCG ATTCATTATG GGCATCCTTT 1860
ACTGACATTC GCACTCTACA GCAGATCATG ACATCTCAAG CGAATAGTAT CTATCAGCAA 1920
CGAGGACTCT GGGCATCAGG AACTGCGAAT TTCTTCCATA AGGATAAATC AGGAACTAAC 1980
CAAGCATTCC GACATAAAAG CTACGGCTAT ATTGTTGGAG GAAGTGCTGA AGATTTTTCT 2040
GAAAATATCT TCAGTGTAGC TTTCTGCCAG CTCTTCGGTA AAGATAAAGA CCTGTTTATA 2100
GTTGAAAATA CCTCTCATAA CTATTTAGCG TCGCTATACC TGCAACATCG AGCATTCCTA 2160
GGAGGACTTC CCATGCCCTC ATTTGGAAGT ATCACCGACA TGCTGAAAGA TATTCCTCTC 2220
ATTTTGAATG CCCAGCTAAG CTACAGCTAC ACTAAAAATG ATATGGATAC TCGCTATACT 2280
TCCTATCCTG AAGCTCAAGG TTCTTGGACC AATAATTCTG GGGCTCTAGA GCTCGGAGGA 2340
TCTCTGGCTC TATATCTCCC TAAAGAAGCA CCGTTCTTCC AGGGATATTT CCCCTTCTTA 2400
AAGTTCCAGG CAGTCTACAG CCGCCAACAA AACTTTAAAG AGAGTGGCGC TGAAGCCCGT 2460
GCTTTTGATG ATGGAGACCT AGTGAACTGC TCTATCCCTG TCGGCATTCG GTTAGAAAAA 2520
ATCTCCGAAG ATGAAAAAAA TAATTTCGAG ATTTCTCTAG CCAACATTGG TGATGTGTAT 2580
CGTAAAAATC CCCGTTCGCG TACTTCTCTA ATGGTCAGTG GAGCCTCTTG GACTTCGCTA 2640
TGTAAAAACC TCGCACGACA AGCCTTCTTA GCAAGTGCTG GAAGCCATCT GACTCTCTCC 2700
CCTCATGTAG AACTCTCTGG GGAAGCTGCT TATGAGCTTC GTGGCTCAGC ACACATCTAC 2760
AATGTAGATT GTGGGCTAAG ATACTCATTC TAG 2793
(2)SEQ ID NO:16的信息:
(i)序列特征:
(A)长度:930氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:16:
Met Lys Ile Pro Leu His Lys Leu Leu Ile Ser Ser Thr Leu Val Thr
1 5 10 15
Pro Ile Leu Leu Ser Ile Ala Thr Tyr Gly Ala Asp Ala Ser Leu Ser
20 25 30
Pro Thr Asp Ser Phe Asp Gly Ala Gly Gly Ser Thr Phe Thr Pro Lys
35 40 45
Ser Thr Ala Asp Ala Asn Gly Thr Asn Tyr Val Leu Ser Gly Asn Val
50 55 60
Tyr Ile Asn Asp Ala Gly Lys Gly Thr Ala Leu Thr Gly Cys Cys Phe
65 70 75 80
Thr Glu Thr Thr Gly Asp Leu Thr Phe Thr Gly Lys Gly Tyr Ser Phe
85 90 95
Ser Phe Asn Thr Val Asp Ala Gly Ser Asn Ala Gly Ala Ala Ala Ser
100 105 110
Thr Thr Ala Asp Lys Ala Leu Thr Phe Thr Gly Phe Ser Asn Leu Ser
115 120 125
Phe Ile Ala Ala Pro Gly Thr Thr Val Ala Ser Gly Lys Ser Thr Leu
130 135 140
Ser Ser Ala Gly Ala Leu Asn Leu Thr Asp Asn Gly Thr Ile Leu Phe
145 150 155 160
Ser Gln Asn Val Ser Asn Glu Ala Asn Asn Asn Gly Gly Ala Ile Thr
165 170 175
Thr Lys Thr Leu Ser Ile Ser Gly Asn Thr Ser Ser Ile Thr Phe Thr
180 185 190
Ser Asn Ser Ala Lys Lys Leu Gly Gly Ala Ile Tyr Ser Ser Ala Ala
195 200 205
Ala Ser Ile Ser Gly Asn Thr Gly Gln Leu Val Phe Met Asn Asn Lys
210 215 220
Gly Glu Thr Gly Gly Gly Ala Leu Gly Phe Glu Ala Ser Ser Ser Ile
225 230 235 240
Thr Gln Asn Ser Ser Leu Phe Phe Ser Gly Asn Thr Ala Thr Asp Ala
245 250 255
Ala Gly Lys Gly Gly Ala Ile Tyr Cys Glu Lys Thr Gly Glu Thr Pro
260 265 270
Thr Leu Thr Ile Ser Gly Asn Lys Ser Leu Thr Phe Ala Glu Asn Ser
275 280 285
Ser Val Thr Gln Gly Gly Ala Ile Cys Ala His Gly Leu Asp Leu Ser
290 295 300
Ala Ala Gly Pro Thr Leu Phe Ser Asn Asn Arg Cys Gly Asn Thr Ala
305 310 315 320
Ala Gly Lys Gly Gly Ala Ile Ala Ile Ala Asp Ser Gly Ser Leu Ser
325 330 335
Leu Ser Ala Asn Gln Gly Asp Ile Thr Phe Leu Gly Asn Thr Leu Thr
340 345 350
Ser Thr Ser Ala Pro Thr Ser Thr Arg Asn Ala Ile Tyr Leu Gly Ser
355 360 365
Ser Ala Lys Ile Thr Asn Leu Arg Ala Ala Gln Gly Gln Ser Ile Tyr
370 375 380
Phe Tyr Asp Pro Ile Ala Ser Asn Thr Thr Gly Ala Ser Asp Val Leu
385 390 395 400
Thr Ile Asn Gln Pro Asp Ser Asn Ser Pro Leu Asp Tyr Ser Gly Thr
405 410 415
Ile Val Phe Ser Gly Glu Lys Leu Ser Ala Asp Glu Ala Lys Ala Ala
420 425 430
Asp Asn Phe Thr Ser Ile Leu Lys Gln Pro Leu Ala Leu Ala Ser Gly
435 440 445
Thr Leu Ala Leu Lys Gly Asn Val Glu Leu Asp Val Asn Gly Phe Thr
450 455 460
Gln Thr Glu Gly Ser Thr Leu Leu Met Gln Pro Gly Thr Lys Leu Lys
465 470 475 480
Ala Asp Thr Glu Ala Ile Ser Leu Thr Lys Leu Val Val Asp Leu Ser
485 490 495
Ala Leu Glu Gly Asn Lys Ser Val Ser Ile Glu Thr Ala Gly Ala Asn
500 505 510
Lys Thr Ile Thr Leu Thr Ser Pro Leu Val Phe Gln Asp Ser Ser Gly
515 520 525
Asn Phe Tyr Glu Ser His Thr Ile Asn Gln Ala Phe Thr Gln Pro Leu
530 535 540
Val Val Phe Thr Ala Ala Thr Ala Ala Ser Asp Ile Tyr Ile Asp Ala
545 550 555 560
Leu Leu Thr Ser Pro Val Gln Thr Pro Glu Pro His Tyr Gly Tyr Gln
565 570 575
Gly His Trp Glu Ala Thr Trp Ala Asp Thr Ser Thr Ala Lys Ser Gly
580 585 590
Thr Met Thr Trp Val Thr Thr Gly Tyr Asn Pro Asn Pro Glu Arg Arg
595 600 605
Ala Ser Val Val Pro Asp Ser Leu Trp Ala Ser Phe Thr Asp Ile Arg
610 615 620
Thr Leu Gln Gln Ile Met Thr Ser Gln Ala Asn Ser Ile Tyr Gln Gln
625 630 635 640
Arg Gly Leu Trp Ala Ser Gly Thr Ala Asn Phe Phe His Lys Asp Lys
645 650 655
Ser Gly Thr Asn Gln Ala Phe Arg His Lys Ser Tyr Gly Tyr Ile Val
660 665 670
Gly Gly Ser Ala Glu Asp Phe Ser Glu Asn Ile Phe Ser Val Ala Phe
675 680 685
Cys Gln Leu Phe Gly Lys Asp Lys Asp Leu Phe Ile Val Glu Asn Thr
690 695 700
Ser His Asn Tyr Leu Ala Ser Leu Tyr Leu Gln His Arg Ala Phe Leu
705 710 715 720
Gly Gly Leu Pro Met Pro Ser Phe Gly Ser Ile Thr Asp Met Leu Lys
725 730 735
Asp Ile Pro Leu Ile Leu Asn Ala Gln Leu Ser Tyr Ser Tyr Thr Lys
740 745 750
Asn Asp Met Asp Thr Arg Tyr Thr Ser Tyr Pro Glu Ala Gln Gly Ser
755 760 765
Trp Thr Asn Asn Ser Gly Ala Leu Glu Leu Gly Gly Ser Leu Ala Leu
770 775 780
Tyr Leu Pro Lys Glu Ala Pro Phe Phe Gln Gly Tyr Phe Pro Phe Leu
785 790 795 800
Lys Phe Gln Ala Val Tyr Ser Arg Gln Gln Asn Phe Lys Glu Ser Gly
805 810 815
Ala Glu Ala Arg Ala Phe Asp Asp Gly Asp Leu Val Asn Cys Ser Ile
820 825 830
Pro Val Gly Ile Arg Leu Glu Lys Ile Ser Glu Asp Glu Lys Asn Asn
835 840 845
Phe Glu Ile Ser Leu Ala Asn Ile Gly Asp Val Tyr Arg Lys Asn Pro
850 855 860
Arg Ser Arg Thr Ser Leu Met Val Ser Gly Ala Ser Trp Thr Ser Leu
865 870 875 880
Cys Lys Asn Leu Ala Arg Gln Ala Phe Leu Ala Ser Ala Gly Ser His
885 890 895
Leu Thr Leu Ser Pro His Val Glu Leu Ser Gly Glu Ala Ala Tyr Glu
900 905 910
Leu Arg Gly Ser Ala His Ile Tyr Asn Val Asp Cys Gly Leu Arg Tyr
915 920 925
Ser Phe
930
(2)SEQ ID NO:17的信息:
(i)序列特征:
(A)长度:840碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:17:
GAAGACAATA TAAGGTACCG TCATAACAGC GGGGGTTATG CACTAGGGAT CACAGCAACA 60
ACTCCTGCCG AGGATCAGCT TACTTTTGCC TTCTGCCAGC TCTTTGCTAG AGATCGCAAT 120
CATATTACAG GTAAGAACCA CGGAGATACT TACGGTGCCT CTTTGTATTT CCACCATACA 180
GAAGGGCTCT TCGACATCGC CAATTTCCTC TGGGGAAAAG CAACCCGAGC TCCCTGGGTG 240
CTCTCTGAGA TCTCCCAGAT CATTCCTTTA TCGTTCGATG CTAAATTCAG TTATCTCCAT 300
ACAGACAACC ACATGAAGAC ATATTATACC GATAACTCTA TCATCAAGGG TTCTTGGAGA 360
AACGATGCCT TCTGTGCAGA TCTTGGAGCT AGCCTGCCTT TTGTTATTTC CGTTCCGTAT 420
CTTCTGAAAG AAGTCGAACC TTTTGTCAAA GTACAGTATA TCTATGCGCA TCAGCAAGAC 480
TTCTACGAGC GTCATGCTGA AGGACGCGCT TTCAATAAAA GCGAGCTTAT CAACGTAGAG 540
ATTCCTATAG GCGTCACCTT CGAAAGAGAC TCAAAATCAG AAAAGGGAAC TTACGATCTT 600
ACTCTTATGT ATATACTCGA TGCTTACCGA CGCAATCCTA AATGTCAAAC TTCCCTAATA 660
GCTAGCGATG CTAACTGGAT GGCCTATGGT ACCAACCTCG CACGACAAGG TTTTTCTGTT 720
CGTGCTGCGA ACCATTTCCA AGTGAACCCC CACATGGAAA TCTTCGGTCA ATTCGCTTTT 780
GAAGTACGAA GTTCTTCACG AAATTATAAT ACAAACCTAG GCTCTAAGTT TTGTTTCTAG 840
(2)SEQ ID NO:18的信息:
(i)序列特征:
(A)长度:279氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:18:
Glu Asp Asn Ile Arg Tyr Arg His Asn Ser Gly Gly Tyr Ala Leu Gly
1 5 10 15
Ile Thr Ala Thr Thr Pro Ala Glu Asp Gln Leu Thr Phe Ala Phe Cys
20 25 30
Gln Leu Phe Ala Arg Asp Arg Asn His Ile Thr Gly Lys Asn His Gly
35 40 45
Asp Thr Tyr Gly Ala Ser Leu Tyr Phe His His Thr Glu Gly Leu Phe
50 55 60
Asp Ile Ala Asn Phe Leu Trp Gly Lys Ala Thr Arg Ala Pro Trp Val
65 70 75 80
Leu Ser Glu Ile Ser Gln Ile Ile Pro Leu Ser Phe Asp Ala Lys Phe
85 90 95
Ser Tyr Leu His Thr Asp Asn His Met Lys Thr Tyr Tyr Thr Asp Asn
100 105 110
Ser Ile Ile Lys Gly Ser Trp Arg Asn Asp Ala Phe Cys Ala Asp Leu
115 120 125
Gly Ala Ser Leu Pro Phe Val Ile Ser Val Pro Tyr Leu Leu Lys Glu
130 135 140
Val Glu Pro Phe Val Lys Val Gln Tyr Ile Tyr Ala His Gln Gln Asp
145 150 155 160
Phe Tyr Glu Arg His Ala Glu Gly Arg Ala Phe Asn Lys Ser Glu Leu
165 170 175
Ile Asn Val Glu Ile Pro Ile Gly Val Thr Phe Glu Arg Asp Ser Lys
180 185 190
Ser Glu Lys Gly Thr Tyr Asp Leu Thr Leu Met Tyr Ile Leu Asp Ala
195 200 205
Tyr Arg Arg Asn Pro Lys Cys Gln Thr Ser Leu Ile Ala Ser Asp Ala
210 215 220
Asn Trp Met Ala Tyr Gly Thr Asn Leu Ala Arg Gln Gly Phe Ser Val
225 230 235 240
Arg Ala Ala Asn His Phe Gln Val Asn Pro His Met Glu Ile Phe Gly
245 250 255
Gln Phe Ala Phe Glu Val Arg Ser Ser Ser Arg Asn Tyr Asn Thr Asn
260 265 270
Leu Gly Ser Lys Phe Cys Phe
275
(2)SEQ ID NO:19的信息:
(i)序列特征:
(A)长度:1545碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:19:
ATGACCATAC TTCGAAATTT TCTTACCTGC TCGGCTTTAT TCCTCGCTCT CCCTGCAGCA 60
GCACAAGTTG TATATCTTCA TGAAAGTGAT GGTTATAACG GTGCTATCAA TAATAAAAGC 120
TTAGAACCTA AAATTACCTG TTATCCAGAA GGAACTTCTT ACATCTTTCT AGATGACGTG 180
AGGATTTCCA ACGTTAAGCA TGATCAAGAA GATGCTGGGG TTTTTATAAA TCGATCTGGG 240
AATCTTTTTT TCATGGGCAA CCGTTGCAAC TTCACTTTTC ACAACCTTAT GACCGAGGGT 300
TTTGGCGCTG CCATTTCGAA CCGCGTTGGA GACACCACTC TCACTCTCTC TAATTTTTCT 360
TACTTAACGT TCACCTCAGC ACCTCTACTA CCTCAAGGAC AAGGAGCGAT TTATAGTCTT 420
GGTTCCGTGA TGATCGAAAA TAGTGAGGAA GTGACTTTCT GTGGGAACTA CTCTTCGTGG 480
AGTGGAGCTG CGATTTATAC TCCCTACCTT TTAGGTTCTA AGGCGAGTCG TCCTTCAGTA 540
AATCTCAGCG GGAACCGCTA CCTGGTGTTT AGAGACTATG TGAGCCAAGG TTATGGCGGC 600
GCCGTATCTA CCCACAATCT CACACTCACG ACTCGAGGAC CTTCGTGTTT TGAAAATAAT 660
CATGCTTATC ATGACGTGAA TAGTAATGGA GGAGCCATTG CCATTGCTCC TGGAGGATCG 720
ATCTCTATAT CCGTGAAAAG CGGAGATCTC ATCTTCAAAG GAAATACAGC ATCACAAGAC 780
GGAAATACAA TACACAACTC CATCCATCTG CAATCTGGAG CACAGTTTAA GAACCTACGT 840
GCTGTTTCAG AATCCGGAGT TTATTTCTAT GATCCTATAA GCCATAGCGA GTCGCATAAA 900
ATTACAGATC TTGTAATCAA TGCTCCTGAA GGAAAGGAAA CTTATGAAGG AACAATTAGC 960
TTCTCAGGAC TATGCCTGGA TGATCATGAA GTTTGTGCGG AAAATCTTAC TTCCACAATC 1020
CTACAAGATG TCACATTAGC AGGAGGAACT CTCTCTCTAT CGGATGGGGT TACCTTGCAA 1080
CTGCATTCTT TTAAGCAGGA AGCAAGCTCT ACGCTTACTA TGTCTCCAGG AACCACTCTG 1140
CTCTGCTCAG GAGATGCTCG GGTTCAGAAT CTGCACATCC TGATTGAAGA TACCGACAAC 1200
TTTGTTCCTG TAAGGATTCG CGCCGAGGAC AAGGATGCTC TTGTCTCATT AGAAAAACTT 1260
AAAGTTGCCT TTGAGGCTTA TTGGTCCGTC TATGACTTTC CTCAATTTAA GGAAGCCTTT 1320
ACGATTCCTC TTCTTGAACT TCTAGGGCCT TCTTTTGACA GTCTTCTCCT AGGGGAGACC 1380
ACTTTGGAGA GAACCCAAGT CACAACAGAG AATGACGCCG TTCGAGGTTT CTGGTCCCTA 1440
AGCTGGGAAG AGTACCCCCC TTCTCTGGAT AAAGACAGAA GGATCACACC AACTAAGAAA 1500
ACTGTTTTCC TCACTTGGAA TCCTGAGATC ACTTCTACGC CATAA 1545
(2)SEQ ID NO:20的信息:
(i)序列特征:
(A)长度:514氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:20:
Met Thr Ile Leu Arg Asn Phe Leu Thr Cys Ser Ala Leu Phe Leu Ala
1 5 10 15
Leu Pro Ala Ala Ala Gln Val Val Tyr Leu His Glu Ser Asp Gly Tyr
20 25 30
Asn Gly Ala Ile Asn Asn Lys Ser Leu Glu Pro Lys Ile Thr Cys Tyr
35 40 45
Pro Glu Gly Thr Ser Tyr Ile Phe Leu Asp Asp Val Arg Ile Ser Asn
50 55 60
Val Lys His Asp Gln Glu Asp Ala Gly Val Phe Ile Asn Arg Ser Gly
65 70 75 80
Asn Leu Phe Phe Met Gly Asn Arg Cys Asn Phe Thr Phe His Asn Leu
85 90 95
Met Thr Glu Gly Phe Gly Ala Ala Ile Ser Asn Arg Val Gly Asp Thr
100 105 110
Thr Leu Thr Leu Ser Asn Phe Ser Tyr Leu Thr Phe Thr Ser Ala Pro
115 120 125
Leu Leu Pro Gln Gly Gln Gly Ala Ile Tyr Ser Leu Gly Ser Val Met
130 135 140
Ile Glu Asn Ser Glu Glu Val Thr Phe Cys Gly Asn Tyr Ser Ser Trp
145 150 155 160
Ser Gly Ala Ala Ile Tyr Thr Pro Tyr Leu Leu Gly Ser Lys Ala Ser
165 170 175
Arg Pro Ser Val Asn Leu Ser Gly Asn Arg Tyr Leu Val Phe Arg Asp
180 185 190
Tyr Val Ser Gln Gly Tyr Gly Gly Ala Val Ser Thr His Asn Leu Thr
195 200 205
Leu Thr Thr Arg Gly Pro Ser Cys Phe Glu Asn Asn His Ala Tyr His
210 215 220
Asp Val Asn Ser Asn Gly Gly Ala Ile Ala Ile Ala Pro Gly Gly Ser
225 230 235 240
Ile Ser Ile Ser Val Lys Ser Gly Asp Leu Ile Phe Lys Gly Asn Thr
245 250 255
Ala Ser Gln Asp Gly Asn Thr Ile His Asn Ser Ile His Leu Gln Ser
260 265 270
Gly Ala Gln Phe Lys Asn Leu Arg Ala Val Ser Glu Ser Gly Val Tyr
275 280 285
Phe Tyr Asp Pro Ile Ser His Ser Glu Ser His Lys Ile Thr Asp Leu
290 295 300
Val Ile Asn Ala Pro Glu Gly Lys Glu Thr Tyr Glu Gly Thr Ile Ser
305 310 315 320
Phe Ser Gly Leu Cys Leu Asp Asp His Glu Val Cys Ala Glu Asn Leu
325 330 335
Thr Ser Thr Ile Leu Gln Asp Val Thr Leu Ala Gly Gly Thr Leu Ser
340 345 350
Leu Ser Asp Gly Val Thr Leu Gln Leu His Ser Phe Lys Gln Glu Ala
355 360 365
Ser Ser Thr Leu Thr Met Ser Pro Gly Thr Thr Leu Leu Cys Ser Gly
370 375 380
Asp Ala Arg Val Gln Asn Leu His Ile Leu Ile Glu Asp Thr Asp Asn
385 390 395 400
Phe Val Pro Val Arg Ile Arg Ala Glu Asp Lys Asp Ala Leu Val Ser
405 410 415
Leu Glu Lys Leu Lys Val Ala Phe Glu Ala Tyr Trp Ser Val Tyr Asp
420 425 430
Phe Pro Gln Phe Lys Glu Ala Phe Thr Ile Pro Leu Leu Glu Leu Leu
435 440 445
Gly Pro Ser Phe Asp Ser Leu Leu Leu Gly Glu Thr Thr Leu Glu Arg
450 455 460
Thr Gln Val Thr Thr Glu Asn Asp Ala Val Arg Gly Phe Trp Ser Leu
465 470 475 480
Ser Trp Glu Glu Tyr Pro Pro Ser Leu Asp Lys Asp Arg Arg Ile Thr
485 490 495
Pro Thr Lys Lys Thr Val Phe Leu Thr Trp Asn Pro Glu Ile Thr Ser
500 505 510
Thr Pro
(2)SEQ ID NO:21的信息:
(i)序列特征:
(A)长度:787碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:21:
ATGAAAACGT CTATTCGTAA GTTCTTAATT TCTACCACAC TGGCGCCATG TTTTGCTTCA 60
ACAGCGTTTA CTGTAGAAGT TATCATGCCT TCCGAGAACT TTGATGGATC GAGTGGGAAG 120
ATTTTTCCTT ACACAACACT TTCTGATCCT AGAGGGACAC TCTGTATTTT TTCAGGGGAT 180
CTCTACATTG CGAATCTTGA TAATGCCATA TCCAGAACCT CTTCCAGTTG CTTTAGCAAT 240
AGGGCGGGAG CACTACAAAT CTTAGGAAAA GGTGGGGTTT TCTCCTTCTT AAATATCCGT 300
TCTTCAGCTG ACGGAGCCGC GATTAGTAGT GTAATCACCC AAAATCCTGA ACTATGTCCC 360
TTGAGTTTTT CAGGATTTAG TCAGATGATC TTCGATAACT GTGAATCTTT GACTTCAGAT 420
ACCTCAGCGA GTAATGTCAT ACCTCACGCA TCGGCGATTT ACGCTACAAC GCCCATGCTC 480
TTTACAAACA ATGACTCCAT ACTATTCCAA TACAACCGTT CTGCAGGATT TGGAGCTGCC 540
ATTCGAGGCA CAAGCATCAC AATAGAAAAT ACGAAAAAGA GCCTTCTCTT TAATGGTAAT 600
GGATCCATCT CTAATGGAGG GGCCCTCACG GGATCTGCAG CGATCAACCT CATCAACAAT 660
AGCGCTCCTG TGATTTTCTC AACGAATGCT ACAGGGATCT ATGGTGGGGC TATTTACCTT 720
ACCGGAGGAT CTATGCTCAC CTCTGGGAAC CTCTCAGGAG TCTTGTTCGT TTATAATAGC 780
TCGCGCT 787
(2)SEQ ID NO:22的信息:
(i)序列特征:
(A)长度:262氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:22:
Met Lys Thr Ser Ile Arg Lys Phe Leu Ile Ser Thr Thr Leu Ala Pro
1 5 10 15
Cys Phe Ala Ser Thr Ala Phe Thr Val Glu Val Ile Met Pro Ser Glu
20 25 30
Asn Phe Asp Gly Ser Ser Gly Lys Ile Phe Pro Tyr Thr Thr Leu Ser
35 40 45
Asp Pro Arg Gly Thr Leu Cys Ile Phe Ser Gly Asp Leu Tyr Ile Ala
50 55 60
Asn Leu Asp Asn Ala Ile Ser Arg Thr Ser Ser Ser Cys Phe Ser Asn
65 70 75 80
Arg Ala Gly Ala Leu Gln Ile Leu Gly Lys Gly Gly Val Phe Ser Phe
85 90 95
Leu Asn Ile Arg Ser Ser Ala Asp Gly Ala Ala Ile Ser Ser Val Ile
100 105 110
Thr Gln Asn Pro Glu Leu Cys Pro Leu Ser Phe Ser Gly Phe Ser Gln
115 120 125
Met Ile Phe Asp Asn Cys Glu Ser Leu Thr Ser Asp Thr Ser Ala Ser
130 135 140
Asn Val Ile Pro His Ala Ser Ala Ile Tyr Ala Thr Thr Pro Met Leu
145 150 155 160
Phe Thr Asn Asn Asp Ser Ile Leu Phe Gln Tyr Asn Arg Ser Ala Gly
165 170 175
Phe Gly Ala Ala Ile Arg Gly Thr Ser Ile Thr Ile Glu Asn Thr Lys
180 185 190
Lys Ser Leu Leu Phe Asn Gly Asn Gly Ser Ile Ser Asn Gly Gly Ala
195 200 205
Leu Thr Gly Ser Ala Ala Ile Asn Leu Ile Asn Asn Ser Ala Pro Val
210 215 220
Ile Phe Ser Thr Asn Ala Thr Gly Ile Tyr Gly Gly Ala Ile Tyr Leu
225 230 235 240
Thr Gly Gly Ser Met Leu Thr Ser Gly Asn Leu Ser Gly Val Leu Phe
245 250 255
Val Tyr Asn Ser Ser Arg
260
(2)SEQ ID NO:23的信息:
(i)序列特征:
(A)长度:2838碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:基因组DNA
(xi)序列描述:SEQ ID NO:23:
ATGAAGACTT CAGTTTCTAT GTTGTTGGCC CTGCTTTGCT CGGGGGCTAG CTCTATTGTA 60
CTCCATGCCG CAACCACTCC ACTAAATCCT GAAGATGGGT TTATTGGGGA GGGCAATACA 120
AATACTTTTT CTCCGAAATC TACAACGGAT GCTGCAGGAA CTACCTACTC TCTCACAGGA 180
GAGGTTCTGT TTATAGATCC GGGGAAAGGT GGTTCAATTA CAGGAACTTG CTTTGTAGAA 240
ACTGCTGGCG ATCTTACATT TTTAGGTAAT GGAAATACCC TAAAGTTCCT GTCGGTAGAT 300
GCAGGTGCTA ATATCGCGGT TGCTCATGTA CAAGGAAGTA AGAATTTAAG CTTCACAGAT 360
TTCCTTTCTC TGGTGATCAC AGAATCTCCA AAATCCGCTG TTAGTACAGG AAAAGGTAGC 420
CTAGTCAGTT CAGGTGCAGT CCAACTGCAA GATATAAACA CTCTAGTTCT TACAAGCAAT 480
GCCTCTGTCG AAGATGGTGG CGTGATTAAA GGAAACTCCT GCTTGATTCA GGGAATCAAA 540
AATAGTGCGA TTTTTGGACA AAATACATCT TCGAAAAAAG GAGGGGCGAT CTCCACGACT 600
CAAGGACTCA CCATAGAGAA TAACTTAGGG ACGCTAAAGT TCAATGAAAA CAAAGCAGTG 660
ACCTCAGGAG GCGCCTTAGA TTTAGGAGCC GCGTCTACAT TCACTGCGAA CCATGAGTTG 720
ATATTTTCAC AAAATAAGAC TTCTGGGAAT GCTGCAAATG GCGGAGCCAT AAATTGCTCA 780
GGCGACCTAA CATTTACTGA TAACACTTCT TTGTTACTTC AAGAAAATAG CACAATGCAG 840
GATGGTGGAG CTTTGTGTAG CACAGGAACC ATAAGCATTA CCGGTAGTGA TTCTATCAAT 900
GTGATAGGAA ATACTTCAGG ACAAAAAGGA GGAGCGATTT CTGCAGCTTC TCTCAAGATT 960
TTGGGAGGGC AGGGAGGCGC TCTCTTTTCT AATAACGTAG TGACTCATGC CACCCCTCTA 1020
GGAGGTGCCA TTTTTATCAA CACAGGAGGA TCCTTGCAGC TCTTCACTCA AGGAGGGGAT 1080
ATCGTATTCG AGGGGAATCA GGTCACTACA ACAGCTCCAA ATGCTACCAC TAAGAGAAAT 1140
GTAATTCACC TCGAGAGCAC CGCGAAGTGG ACGGGACTTG CTGCAAGTCA AGGTAACGCT 1200
ATCTATTTCT ATGATCCCAT TACCACCAAC GATACGGGAG CAAGCGATAA CTTACGTATC 1260
AATGAGGTCA GTGCAAATCA AAAGCTCTCG GGATCTATAG TATTTTCTGG AGAGAGATTG 1320
TCGACAGCAG AAGCTATAGC TGAAAATCTT ACTTCGAGGA TCAACCAGCC TGTCACTTTA 1380
GTAGAGGGGA GCTTAGAACT TAAACAGGGA GTGACCTTGA TCACACAAGG ATTCTCGCAG 1440
GAGCCAGAAT CCACGCTTCT TTTGGATTTG GGGACCTCAT TACAAGCTTC TACAGAAGAT 1500
ATCGTCATCA CAAATTCATC TATAAATGCC GATACCATTT ACGGAAAGAA TCCAATCAAT 1560
ATTGTAGCTT CAGCAGCGAA TAAGAACATT ACCCTAACAG GAACCTTAGC ACTTGTAAAT 1620
GCAGATGGAG CTTTGTATGA GAACCATACC TTGCAAGACT CTCAAGATTA TAGCTTTGTA 1680
AAGTTATCTC CAGGAGCGGG AGGGACTATA ATTACTCAAG ATGCTTCTCA GAAGCTTCTT 1740
GAAGTAGCTC CTTCTAGACC ACATTATGGC TATCAAGGAC ATTGGAATGT GCAAGTCATC 1800
CCAGGAACGG GAACTCAACC GAGCCAGGCA AATTTAGAAT GGGTGCGGAC AGGATACCTT 1860
CCGAATCCCG AACGGCAAGG ATTTTTAGTT CCCAATAGCC TGTGGGGTTC TTTTGTTGAT 1920
CAGCGTGCTA TCCAAGAAAT CATGGTAAAT AGTAGCCAAA TCTTATGTCA GGAACGGGGA 1980
GTCTGGGGAG CTGGAATTGC TAATTTCCTA CATAGAGATA AAATTAATGA GCACGGCTAT 2040
CGCCATAGCG GTGTCGGTTA TCTTGTGGGA GTTGGCACTC ATGCTTTTTC TGATGCTACG 2100
ATAAATGCGG CTTTTTGCCA GCTCTTCAGT AGAGATAAAG ACTACGTAGT ATCCAAAAAT 2160
CATGGAACTA GCTACTCAGG GGTCGTATTT CTTGAGGATA CCCTAGAGTT TAGAAGTCCA 2220
CAGGGATTCT ATACTGATAG CTCCTCAGAA GCTTGCTGTA ACCAAGTCGT CACTATAGAT 2280
ATGCAGTTGT CTTACAGCCA TAGAAATAAT GATATGAAAA CCAAATACAC GACATATCCA 2340
GAAGCTCAGG GATCTTGGGC AAATGATGTT TTTGGTCTTG AGTTTGGAGC GACTACATAC 2400
TACTACCCTA ACAGTACTTT TTTATTTGAT TACTACTCTC CGTTTCTCAG GCTGCAGTGC 2460
ACCTATGCTC ACCAGGAAGA CTTCAAAGAG ACAGGAGGTG AGGTTCGTCA CTTTACTAGC 2520
GGAGATCTTT TCAATTTAGC AGTTCCTATT GGCGTGAAGT TTGAGAGATT TTCAGACTGT 2580
AAAAGGGGAT CTTATGAACT TACCCTTGCT TATGTTCCTG ATGTGATTCG CAAAGATCCC 2640
AAGAGCACGG CAACATTGGC TAGTGGAGCT ACGTGGAGCA CCCACGGAAA CAATCTCTCC 2700
AGACAAGGAT TACAACTGCG TTTAGGGAAC CACTGTCTCA TAAATCCTGG AATTGAGGTG 2760
TTCAGTCACG GAGCTATTGA ATTGCGGGGA TCCTCTCGTA ATTATAACAT CAATCTCGGG 2820
GGTAAATACC GATTTTAA 2838
(2)SEQ ID NO:24的信息:
(i)序列特征:
(A)长度:946氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:肽
(xi)序列描述:SEQ ID NO:24:
Met Lys Thr Ser Val Ser Met Leu Leu Ala Leu Leu Cys Ser Gly Ala
1 5 10 15
Ser Ser Ile Val Leu His Ala Ala Thr Thr Pro Leu Asn Pro Glu Asp
20 25 30
Gly Phe Ile Gly Glu Gly Asn Thr Asn Thr Phe Ser Pro Lys Ser Thr
35 40 45
Thr Asp Ala Ala Gly Thr Thr Tyr Ser Leu Thr Gly Glu Val Leu Phe
50 55 60
Ile Asp Pro Gly Lys Gly Gly Ser Ile Thr Gly Thr Cys Phe Val Glu
65 70 75 80
Thr Ala Gly Asp Leu Thr Phe Leu Gly Asn Gly Asn Thr Leu Lys Phe
85 90 95
Leu Ser Val Asp Ala Gly Ala Asn Ile Ala Val Ala His Val Gln Gly
100 105 110
Ser Lys Asn Leu Ser Phe Thr Asp Phe Leu Ser Leu Val Ile Thr Glu
115 120 125
Ser Pro Lys Ser Ala Val Ser Thr Gly Lys Gly Ser Leu Val Ser Ser
130 135 110
Gly Ala Val Gln Leu Gln Asp Ile Asn Thr Leu Val Leu Thr Ser Asn
145 150 155 160
Ala Ser Val Glu Asp Gly Gly Val Ile Lys Gly Asn Ser Cys Leu Ile
165 170 175
Gln Gly Ile Lys Asn Ser Ala Ile Phe Gly Gln Asn Thr Ser Ser Lys
180 185 190
Lys Gly Gly Ala Ile Ser Thr Thr Gln Gly Leu Thr Ile Glu Asn Asn
195 200 205
Leu Gly Thr Leu Lys Phe Asn Glu Asn Lys Ala Val Thr Ser Gly Gly
210 215 220
Ala Leu Asp Leu Gly Ala Ala Ser Thr Phe Thr Ala Asn His Glu Leu
225 230 235 240
Ile Phe Ser Gln Asn Lys Thr Ser Gly Asn Ala Ala Asn Gly Gly Ala
245 250 255
Ile Asn Cys Ser Gly Asp Leu Thr Phe Thr Asp Asn Thr Ser Leu Leu
260 265 270
Leu Gln Glu Asn Ser Thr Met Gln Asp Gly Gly Ala Leu Cys Ser Thr
275 280 285
Gly Thr Ile Ser Ile Thr Gly Ser Asp Ser Ile Asn Val Ile Gly Asn
290 295 300
Thr Ser Gly Gln Lys Gly Gly Ala Ile Ser Ala Ala Ser Leu Lys Ile
305 310 315 320
Leu Gly Gly Gln Gly Gly Ala Leu Phe Ser Asn Asn Val Val Thr His
325 330 335
Ala Thr Pro Leu Gly Gly Ala Ile Phe Ile Asn Thr Gly Gly Ser Leu
340 345 350
Gln Leu Phe Thr Gln Gly Gly Asp Ile Val Phe Glu Gly Asn Gln Val
355 360 365
Thr Thr Thr Ala Pro Asn Ala Thr Thr Lys Arg Asn Val Ile His Leu
370 375 380
Glu Ser Thr Ala Lys Trp Thr Gly Leu Ala Ala Ser Gln Gly Asn Ala
385 390 395 400
Ile Tyr Phe Tyr Asp Pro Ile Thr Thr Asn Asp Thr Gly Ala Ser Asp
405 410 415
Asn Leu Arg Ile Asn Glu Val Ser Ala Asn Gln Lys Leu Ser Gly Ser
420 425 430
Ile Val Phe Ser Gly Glu Arg Leu Ser Thr Ala Glu Ala Ile Ala Glu
435 440 445
Asn Leu Thr Ser Arg Ile Asn Gln Pro Val Thr Leu Val Glu Gly Ser
450 455 460
Leu Glu Leu Lys Gln Gly Val Thr Leu Ile Thr Gln Gly Phe Ser Gln
465 470 475 480
Glu Pro Glu Ser Thr Leu Leu Leu Asp Leu Gly Thr Ser Leu Gln Ala
485 490 495
Ser Thr Glu Asp Ile Val Ile Thr Asn Ser Ser Ile Asn Ala Asp Thr
500 505 510
Ile Tyr Gly Lys Asn Pro Ile Asn Ile Val Ala Ser Ala Ala Asn Lys
515 520 525
Asn Ile Thr Leu Thr Gly Thr Leu Ala Leu Val Asn Ala Asp Gly Ala
530 535 540
Leu Tyr Glu Asn His Thr Leu Gln Asp Ser Gln Asp Tyr Ser Phe Val
545 550 555 560
Lys Leu Ser Pro Gly Ala Gly Gly Thr Ile Ile Thr Gln Asp Ala Ser
565 570 575
Gln Lys Leu Leu Glu Val Ala Pro Ser Arg Pro His Tyr Gly Tyr Gln
580 585 590
Gly His Trp Asn Val Gln Val Ile Pro Gly Thr Gly Thr Gln Pro Ser
595 600 605
Gln Ala Asn Leu Glu Trp Val Arg Thr Gly Tyr Leu Pro Asn Pro Glu
610 615 620
Arg Gln Gly Phe Leu Val Pro Asn Ser Leu Trp Gly Ser Phe Val Asp
625 630 635 640
Gln Arg Ala Ile Gln Glu Ile Met Val Asn Ser Ser Gln Ile Leu Cys
645 650 655
Gln Glu Arg Gly Val Trp Gly Ala Gly Ile Ala Asn Phe Leu His Arg
660 665 670
Asp Lys Ile Asn Glu His Gly Tyr Arg His Ser Gly Val Gly Tyr Leu
675 680 685
Val Gly Val Gly Thr His Ala Phe Ser Asp Ala Thr Ile Asn Ala Ala
690 695 700
Phe Cys Gln Leu Phe Ser Arg Asp Lys Asp Tyr Val Val Ser Lys Asn
705 710 715 720
His Gly Thr Ser Tyr Ser Gly Val Val Phe Leu Glu Asp Thr Leu Glu
725 730 735
Phe Arg Ser Pro Gln Gly Phe Tyr Thr Asp Ser Ser Ser Glu Ala Cys
740 745 750
Cys Asn Gln Val Val Thr Ile Asp Met Gln Leu Ser Tyr Ser His Arg
755 760 765
Asn Asn Asp Met Lys Thr Lys Tyr Thr Thr Tyr Pro Glu Ala Gln Gly
770 775 780
Ser Trp Ala Asn Asp Val Phe Gly Leu Glu Phe Gly Ala Thr Thr Tyr
785 790 795 800
Tyr Tyr Pro Asn Ser Thr Phe Leu Phe Asp Tyr Tyr Ser Pro Phe Leu
805 810 815
Arg Leu Gln Cys Thr Tyr Ala His Gln Glu Asp Phe Lys Glu Thr Gly
820 825 830
Gly Glu Val Arg His Phe Thr Ser Gly Asp Leu Phe Asn Leu Ala Val
835 840 845
Pro Ile Gly Val Lys Phe Glu Arg Phe Ser Asp Cys Lys Arg Gly Ser
850 855 860
Tyr Glu Leu Thr Leu Ala Tyr Val Pro Asp Val Ile Arg Lys Asp Pro
865 870 875 880
Lys Ser Thr Ala Thr Leu Ala Ser Gly Ala Thr Trp Ser Thr His Gly
885 890 895
Asn Asn Leu Ser Arg Gln Gly Leu Gln Leu Arg Leu Gly Asn His Cys
900 905 910
Leu Ile Asn Pro Gly Ile Glu Val Phe Ser His Gly Ala Ile Glu Leu
915 920 925
Arg Gly Ser Ser Arg Asn Tyr Asn Ile Asn Leu Gly Gly Lys Tyr Arg
930 935 940
Phe
945
(2)SEQ ID NO:25的信息:
(i)序列特征:
(A)长度:3000碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ix)特征:
(A)名称/关键字:编码序列
(B)位置:259...3000
(D)其它信息:
(xi)序列描述:SEQ ID NO:25:
ATCAGGTGAT AAAAGTTCCT CGTTAGCTAG TGACTGTAGG TGACATGAGA AAGCTAACAC 60
GGAGGAAACT AAAACCCAAG GAATCGAAGT CTTCATGGTA ATGCTTTTGT TTTTTAGAGA 120
ACTATTCGCA TCAATATAGA AACAAAATAA GTAAATCAAG TTAAAGATGA CAAAACAGCT 180
GTCAAGAATT TTTATCTTGA CTCTCTGAGT TTTCTATTTT ATATGACGCA AGTAAGAATT 240
TAATAATAAA GTGGGTTT ATG AAA TCG CAA TTT TCC TGG TTA GTG CTC TCT 291
Met Lys Ser Gln Phe Ser Trp Leu Val Leu Ser
1 5 10
TCG ACA TTG GCA TGT TTT ACT AGT TGT TCC ACT GTT TTT GCT GCA ACT 339
Ser Thr Leu Ala Cys Phe Thr Ser Cys Ser Thr Val Phe Ala Ala Thr
15 20 25
GCT GAA AAT ATA GGC CCC TCT GAT AGC TTT GAC GGA AGT ACT AAC ACA 387
Ala Glu Asn Ile Gly Pro Ser Asp Ser Phe Asp Gly Ser Thr Asn Thr
30 35 40
GGC ACC TAT ACT CCT AAA AAT ACG ACT ACT GGA ATA GAC TAT ACT CTG 435
Gly Thr Tyr Thr Pro Lys Asn Thr Thr Thr Gly Ile Asp Tyr Thr Leu
45 50 55
ACA GGA GAT ATA ACT CTG CAA AAC CTT GGG GAT TCG GCA GCT TTA ACG 483
Thr Gly Asp Ile Thr Leu Gln Asn Leu Gly Asp Ser Ala Ala Leu Thr
60 65 70 75
AAG GGT TGT TTT TCT GAC ACT ACG GAA TCT TTA AGC TTT GCC GGT AAG 531
Lys Gly Cys Phe Ser Asp Thr Thr Glu Ser Leu Ser Phe Ala Gly Lys
80 85 90
GGG TAC TCA CTT TCT TTT TTA AAT ATT AAG TCT AGT GCT GAA GGC GCA 579
Gly Tyr Ser Leu Ser Phe Leu Asn Ile Lys Ser Ser Ala Glu Gly Ala
95 100 105
GCA CTT TCT GTT ACA ACT GAT AAA AAT CTG TCG CTA ACA GGA TTT TCG 627
Ala Leu Ser Val Thr Thr Asp Lys Asn Leu Ser Leu Thr Gly Phe Ser
110 115 120
AGT CTT ACT TTC TTA GCG GCC CCA TCA TCG GTA ATC ACA ACC CCC TCA 675
Ser Leu Thr Phe Leu Ala Ala Pro Ser Ser Val Ile Thr Thr Pro Ser
125 130 135
GGA AAA GGT GCA GTT AAA TGT GGA GGG GAT CTT ACA TTT GAT AAC AAT 723
Gly Lys Gly Ala Val Lys Cys Gly Gly Asp Leu Thr Phe Asp Asn Asn
140 145 150 155
GGA ACT ATT TTA TTT AAA CAA GAT TAC TGT GAG GAA AAT GGC GGA GCC 771
Gly Thr Ile Leu Phe Lys Gln Asp Tyr Cys Glu Glu Asn Gly Gly Ala
160 165 170
ATT TCT ACC AAG AAT CTT TCT TTG AAA AAC AGC ACG GGA TCG ATT TCT 819
Ile Ser Thr Lys Asn Leu Ser Leu Lys Asn Ser Thr Gly Ser Ile Ser
175 180 185
TTT GAA GGG AAT AAA TCG AGC GCA ACA GGG AAA AAA GGT GGG GCT ATT 867
Phe Glu Gly Asn Lys Ser Ser Ala Thr Gly Lys Lys Gly Gly Ala Ile
190 195 200
TGT GCT ACT GGT ACT GTA GAT ATT ACA AAT AAT ACG GCT CCT ACC CTC 915
Cys Ala Thr Gly Thr Val Asp Ile Thr Asn Asn Thr Ala Pro Thr Leu
205 210 215
TTC TCG AAC AAT ATT GCT GAA GCT GCA GGT GGA GCT ATA AAT AGC ACA 963
Phe Ser Asn Asn Ile Ala Glu Ala Ala Gly Gly Ala Ile Asn Ser Thr
220 225 230 235
GGA AAC TGT ACA ATT ACA GGG AAT ACG TCT CTT GTA TTT TCT GAA AAT 1011
Gly Asn Cys Thr Ile Thr Gly Asn Thr Ser Leu Val Phe Ser Glu Asn
240 245 250
AGT GTG ACA GCG ACC GCA GGA AAT GGA GGA GCT CTT TCT GGA GAT GCC 1059
Ser Val Thr Ala Thr Ala Gly Asn Gly Gly Ala Leu Ser Gly Asp Ala
255 260 265
GAT GTT ACC ATA TCT GGG AAT CAG AGT GTA ACT TTC TCA GGA AAC CAA 1107
Asp Val Thr Ile Ser Gly Asn Gln Ser Val Thr Phe Ser Gly Asn Gln
270 275 280
GCT GTA GCT AAT GGC GGA GCC ATT TAT GCT AAG AAG CTT ACA CTG GCT 1155
Ala Val Ala Asn Gly Gly Ala Ile Tyr Ala Lys Lys Leu Thr Leu Ala
285 290 295
TCC GGG GGG GGG GGG GGT ATC TCC TTT TCT AAC AAT ATA GTC CAA GGT 1203
Ser Gly Gly Gly Gly Gly Ile Ser Phe Ser Asn Asn Ile Val Gln Gly
300 305 310 315
ACC ACT GCA GGT AAT GGT GGA GCC ATT TCT ATA CTG GCA GCT GGA GAG 1251
Thr Thr Ala Gly Asn Gly Gly Ala Ile Ser Ile Leu Ala Ala Gly Glu
320 325 330
TGT AGT CTT TCA GCA GAA GCA GGG GAC ATT ACC TTC AAT GGG AAT GCC 1299
Cys Ser Leu Ser Ala Glu Ala Gly Asp Ile Thr Phe Asn Gly Asn Ala
335 340 345
ATT GTT GCA ACT ACA CCA CAA ACT ACA AAA AGA AAT TCT ATT GAC ATA 1347
Ile Val Ala Thr Thr Pro Gln Thr Thr Lys Arg Asn Ser Ile Asp Ile
350 355 360
GGA TCT ACT GCA AAG ATC ACG AAT TTA CGT GCA ATA TCT GGG CAT AGC 1395
Gly Ser Thr Ala Lys Ile Thr Asn Leu Arg Ala Ile Ser Gly His Ser
365 370 375
ATC TTT TTC TAC GAT CCG ATT ACT GCT AAT ACG GCT GCG GAT TCT ACA 1443
Ile Phe Phe Tyr Asp Pro Ile Thr Ala Asn Thr Ala Ala Asp Ser Thr
380 385 390 395
GAT ACT TTA AAT CTC AAT AAG GCT GAT GCA GGT AAT AGT ACA GAT TAT 1491
Asp Thr Leu Asn Leu Asn Lys Ala Asp Ala Gly Asn Ser Thr Asp Tyr
400 405 410
AGT GGG TCG ATT GTT TTT TCT GGT GAA AAG CTC TCT GAA GAT GAA GCA 1539
Ser Gly Ser Ile Val Phe Ser Gly Glu Lys Leu Ser Glu Asp Glu Ala
415 420 425
AAA GTT GCA GAC AAC CTC ACT TCT ACG CTG AAG CAG CCT GTA ACT CTA 1587
Lys Val Ala Asp Asn Leu Thr Ser Thr Leu Lys Gln Pro Val Thr Leu
430 435 440
ACT GCA GGA AAT TTA GTA CTT AAA CGT GGT GTC ACT CTC GAT ACG AAA 1635
Thr Ala Gly Asn Leu Val Leu Lys Arg Gly Val Thr Leu Asp Thr Lys
445 450 455
GGC TTT ACT CAG ACC GCG GGT TCC TCT GTT ATT ATG GAT GCG GGC ACA 1683
Gly Phe Thr Gln Thr Ala Gly Ser Ser Val Ile Met Asp Ala Gly Thr
460 465 470 475
ACG TTA AAA GCA AGT ACA GAG GAG GTC ACT TTA ACA GGT CTT TCC ATT 1731
Thr Leu Lys Ala Ser Thr Glu Glu Val Thr Leu Thr Gly Leu Ser Ile
480 485 490
CCT GTA GAC TCT TTA GGC GAG GGT AAG AAA GTT GTA ATT GCT GCT TCT 1779
Pro Val Asp Ser Leu Gly Glu Gly Lys Lys Val Val Ile Ala Ala Ser
495 500 505
GCA GCA AGT AAA AAT GTA GCC CTT AGT GGT CCG ATT CTT CTT TTG GAT 1827
Ala Ala Ser Lys Asn Val Ala Leu Ser Gly Pro Ile Leu Leu Leu Asp
510 515 520
AAC CAA GGG AAT GCT TAT GAA AAT CAC GAC TTA GGA AAA ACT CAA GAC 1875
Asn Gln Gly Asn Ala Tyr Glu Asn His Asp Leu Gly Lys Thr Gln Asp
525 530 535
TTT TCA TTT GTG CAG CTC TCT GCT CTG GGT ACT GCA ACA ACT ACA GAT 1923
Phe Ser Phe Val Gln Leu Ser Ala Leu Gly Thr Ala Thr Thr Thr Asp
540 545 550 555
GTT CCA GCG GTT CCT ACA GTA GCA ACT CCT ACG CAC TAT GGG TAT CAA 1971
Val Pro Ala Val Pro Thr Val Ala Thr Pro Thr His Tyr Gly Tyr Gln
560 565 570
GGT ACT TGG GGA ATG ACT TGG GTT GAT GAT ACC GCA AGC ACT CCA AAG 2019
Gly Thr Trp Gly Met Thr Trp Val Asp Asp Thr Ala Ser Thr Pro Lys
575 580 585
ACT AAG ACA GCG ACA TTA GCT TGG ACC AAT ACA GGC TAC CTT CCG AAT 2067
Thr Lys Thr Ala Thr Leu Ala Trp Thr Asn Thr Gly Tyr Leu Pro Asn
590 595 600
CCT GAG CGT CAA GGA CCT TTA GTT CCT AAT AGC CTT TGG GGA TCT TTT 2115
Pro Glu Arg Gln Gly Pro Leu Val Pro Asn Ser Leu Trp Gly Ser Phe
605 610 615
TCA GAC ATC CAA GCG ATT CAA GGT GTC ATA GAG AGA AGT GCT TTG ACT 2163
Ser Asp Ile Gln Ala Ile Gln Gly Val Ile Glu Arg Ser Ala Leu Thr
620 625 630 635
CTT TGT TCA GAT CGA GGC TTC TGG GCT GCG GGA GTC GCC AAT TTC TTA 2211
Leu Cys Ser Asp Arg Gly Phe Trp Ala Ala Gly Val Ala Asn Phe Leu
640 645 650
GAT AAA GAT AAG AAA GGG GAA AAA CGC AAA TAC CGT CAT AAA TCT GGT 2259
Asp Lys Asp Lys Lys Gly Glu Lys Arg Lys Tyr Arg His Lys Ser Gly
655 660 665
GGA TAT GCT ATC GGA GGT GCA GCG CAA ACT TGT TCT GAA AAC TTA ATT 2307
Gly Tyr Ala Ile Gly Gly Ala Ala Gln Thr Cys Ser Glu Asn Leu Ile
670 675 680
AGC TTT GCC TTT TGC CAA CTC TTT GGT AGC GAT AAA GAT TTC TTA GTC 2355
Ser Phe Ala Phe Cys Gln Leu Phe Gly Ser Asp Lys Asp Phe Leu Val
685 690 695
GCT AAA AAT CAT ACT GAT ACC TAT GCA GGA GCC TTC TAT ATC CAA CAC 2403
Ala Lys Asn His Thr Asp Thr Tyr Ala Gly Ala Phe Tyr Ile Gln His
700 705 710 715
ATT ACA GAA TGT AGT GGG TTC ATA GGT TGT CTC TTA GAT AAA CTT CCT 2451
Ile Thr Glu Cys Ser Gly Phe Ile Gly Cys Leu Leu Asp Lys Leu Pro
720 725 730
GGC TCT TGG AGT CAT AAA CCC CTC GTT TTA GAA GGG CAG CTC GCT TAT 2499
Gly Ser Trp Ser His Lys Pro Leu Val Leu Glu Gly Gln Leu Ala Tyr
735 740 745
AGC CAC GTC AGT AAT GAT CTG AAG ACA AAG TAT ACT GCG TAT CCT GAG 2547
Ser His Val Ser Asn Asp Leu Lys Thr Lys Tyr Thr Ala Tyr Pro Glu
750 755 760
GTG AAA GGT TCT TGG GGG AAT AAT GCT TTT AAC ATG ATG TTG GGA GCT 2595
Val Lys Gly Ser Trp Gly Asn Asn Ala Phe Asn Met Met Leu Gly Ala
765 770 775
TCT TCT CAT TCT TAT CCT GAA TAC CTG CAT TGT TTT GAT ACC TAT GCT 2643
Ser Ser His Ser Tyr Pro Glu Tyr Leu His Cys Phe Asp Thr Tyr Ala
780 785 790 795
CCA TAC ATC AAA CTG AAT CTG ACC TAT ATA CGT CAG GAC AGC TTC TCG 2691
Pro Tyr Ile Lys Leu Asn Leu Thr Tyr Ile Arg Gln Asp Ser Phe Ser
800 805 810
GAG AAA GGT ACA GAA GGA AGA TCT TTT GAT GAC AGC AAC CTC TTC AAT 2739
Glu Lys Gly Thr Glu Gly Arg Ser Phe Asp Asp Ser Asn Leu Phe Asn
815 820 825
TTA TCT TTG CCT ATA GGG GTG AAG TTT GAG AAG TTC TCT GAT TGT AAT 2787
Leu Ser Leu Pro Ile Gly Val Lys Phe Glu Lys Phe Ser Asp Cys Asn
830 835 840
GAC TTT TCT TAT GAT CTG ACT TTA TCC TAT GTT CCT GAT CTT ATC CGC 2835
Asp Phe Ser Tyr Asp Leu Thr Leu Ser Tyr Val Pro Asp Leu Ile Arg
845 850 855
AAT GAT CCC AAA TGC ACT ACA GCA CTT GTA ATC AGC GGA GCC TCT TGG 2883
Asn Asp Pro Lys Cys Thr Thr Ala Leu Val Ile Ser Gly Ala Ser Trp
860 865 870 875
GAA ACT TAT GCC AAT AAC TTA GCA CGA CAG GCC TTG CAA GTG CGT GCA 2931
Glu Thr Tyr Ala Asn Asn Leu Ala Arg Gln Ala Leu Gln Val Arg Ala
880 885 890
GGC AGT CAC TAC GCC TTC TCT CCT ATG TTT GAA GTG CTC GGC CAG TTT 2979
Gly Ser His Tyr Ala Phe Ser Pro Met Phe Glu Val Leu Gly Gln Phe
895 900 905
GTC TTT GAA GTT CGT GGA TCC 3000
Val Phe Glu Val Arg Gly Ser
910
(2)SEQ ID NO:26的信息:
(i)序列特征:
(A)长度:914氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白质
(v)片段类型:内部
(xi)序列描述:SEQ ID NO:26:
Met Lys Ser Gln Phe Ser Trp Leu Val Leu Ser Ser Thr Leu Ala Cys
1 5 10 15
Phe Thr Ser Cys Ser Thr Val Phe Ala Ala Thr Ala Glu Asn Ile Gly
20 25 30
Pro Ser Asp Ser Phe Asp Gly Ser Thr Asn Thr Gly Thr Tyr Thr Pro
35 40 45
Lys Asn Thr Thr Thr Gly Ile Asp Tyr Thr Leu Thr Gly Asp Ile Thr
50 55 60
Leu Gln Asn Leu Gly Asp Ser Ala Ala Leu Thr Lys Gly Cys Phe Ser
65 70 75 80
Asp Thr Thr Glu Ser Leu Ser Phe Ala Gly Lys Gly Tyr Ser Leu Ser
85 90 95
Phe Leu Asn Ile Lys Ser Ser Ala Glu Gly Ala Ala Leu Ser Val Thr
100 105 110
Thr Asp Lys Asn Leu Ser Leu Thr Gly Phe Ser Ser Leu Thr Phe Leu
115 120 125
Ala Ala Pro Ser Ser Val Ile Thr Thr Pro Ser Gly Lys Gly Ala Val
130 135 140
Lys Cys Gly Gly Asp Leu Thr Phe Asp Asn Asn Gly Thr Ile Leu Phe
145 150 155 160
Lys Gln Asp Tyr Cys Glu Glu Asn Gly Gly Ala Ile Ser Thr Lys Asn
165 170 175
Leu Ser Leu Lys Asn Ser Thr Gly Ser Ile Ser Phe Glu Gly Asn Lys
180 185 190
Ser Ser Ala Thr Gly Lys Lys Gly Gly Ala Ile Cys Ala Thr Gly Thr
195 200 205
Val Asp Ile Thr Asn Asn Thr Ala Pro Thr Leu Phe Ser Asn Asn Ile
210 215 220
Ala Glu Ala Ala Gly Gly Ala Ile Asn Ser Thr Gly Asn Cys Thr Ile
225 230 235 240
Thr Gly Asn Thr Ser Leu Val Phe Ser Glu Asn Ser Val Thr Ala Thr
245 250 255
Ala Gly Asn Gly Gly Ala Leu Ser Gly Asp Ala Asp Val Thr Ile Ser
260 265 270
Gly Asn Gln Ser Val Thr Phe Ser Gly Asn Gln Ala Val Ala Asn Gly
275 280 285
Gly Ala Ile Tyr Ala Lys Lys Leu Thr Leu Ala Ser Gly Gly Gly Gly
290 295 300
Gly Ile Ser Phe Ser Asn Asn Ile Val Gln Gly Thr Thr Ala Gly Asn
305 310 315 320
Gly Gly Ala Ile Ser Ile Leu Ala Ala Gly Glu Cys Ser Leu Ser Ala
325 330 335
Glu Ala Gly Asp Ile Thr Phe Asn Gly Asn Ala Ile Val Ala Thr Thr
340 345 350
Pro Gln Thr Thr Lys Arg Asn Ser Ile Asp Ile Gly Ser Thr Ala Lys
355 360 365
Ile Thr Asn Leu Arg Ala Ile Ser Gly His Ser Ile Phe Phe Tyr Asp
370 375 380
Pro Ile Thr Ala Asn Thr Ala Ala Asp Ser Thr Asp Thr Leu Asn Leu
385 390 395 400
Asn Lys Ala Asp Ala Gly Asn Ser Thr Asp Tyr Ser Gly Ser Ile Val
405 410 415
Phe Ser Gly Glu Lys Leu Ser Glu Asp Glu Ala Lys Val Ala Asp Asn
420 425 430
Leu Thr Ser Thr Leu Lys Gln Pro Val Thr Leu Thr Ala Gly Asn Leu
435 440 445
Val Leu Lys Arg Gly Val Thr Leu Asp Thr Lys Gly Phe Thr Gln Thr
450 455 460
Ala Gly Ser Ser Val Ile Met Asp Ala Gly Thr Thr Leu Lys Ala Ser
465 470 475 480
Thr Glu Glu Val Thr Leu Thr Gly Leu Ser Ile Pro Val Asp Ser Leu
485 490 495
Gly Glu Gly Lys Lys Val Val Ile Ala Ala Ser Ala Ala Ser Lys Asn
500 505 510
Val Ala Leu Ser Gly Pro Ile Leu Leu Leu Asp Asn Gln Gly Asn Ala
515 520 525
Tyr Glu Asn His Asp Leu Gly Lys Thr Gln Asp Phe Ser Phe Val Gln
530 535 540
Leu Ser Ala Leu Gly Thr Ala Thr Thr Thr Asp Val Pro Ala Val Pro
545 550 555 560
Thr Val Ala Thr Pro Thr His Tyr Gly Tyr Gln Gly Thr Trp Gly Met
565 570 575
Thr Trp Val Asp Asp Thr Ala Ser Thr Pro Lys Thr Lys Thr Ala Thr
580 585 590
Leu Ala Trp Thr Asn Thr Gly Tyr Leu Pro Asn Pro Glu Arg Gln Gly
595 600 605
Pro Leu Val Pro Asn Ser Leu Trp Gly Ser Phe Ser Asp Ile Gln Ala
610 615 620
Ile Gln Gly Val Ile Glu Arg Ser Ala Leu Thr Leu Cys Ser Asp Arg
625 630 635 640
Gly Phe Trp Ala Ala Gly Val Ala Asn Phe Leu Asp Lys Asp Lys Lys
645 650 655
Gly Glu Lys Arg Lys Tyr Arg His Lys Ser Gly Gly Tyr Ala Ile Gly
660 665 670
Gly Ala Ala Gln Thr Cys Ser Glu Asn Leu Ile Ser Phe Ala Phe Cys
675 680 685
Gln Leu Phe Gly Ser Asp Lys Asp Phe Leu Val Ala Lys Asn His Thr
690 695 700
Asp Thr Tyr Ala Gly Ala Phe Tyr Ile Gln His Ile Thr Glu Cys Ser
705 710 715 720
Gly Phe Ile Gly Cys Leu Leu Asp Lys Leu Pro Gly Ser Trp Ser His
725 730 735
Lys Pro Leu Val Leu Glu Gly Gln Leu Ala Tyr Ser His Val Ser Asn
740 745 750
Asp Leu Lys Thr Lys Tyr Thr Ala Tyr Pro Glu Val Lys Gly Ser Trp
755 760 765
Gly Asn Asn Ala Phe Asn Met Met Leu Gly Ala Ser Ser His Ser Tyr
770 775 780
Pro Glu Tyr Leu His Cys Phe Asp Thr Tyr Ala Pro Tyr Ile Lys Leu
785 790 795 800
Asn Leu Thr Tyr Ile Arg Gln Asp Ser Phe Ser Glu Lys Gly Thr Glu
805 810 815
Gly Arg Ser Phe Asp Asp Ser Asn Leu Phe Asn Leu Ser Leu Pro Ile
820 825 830
Gly Val Lys Phe Glu Lys Phe Ser Asp Cys Asn Asp Phe Ser Tyr Asp
835 840 845
Leu Thr Leu Ser Tyr Val Pro Asp Leu Ile Arg Asn Asp Pro Lys Cys
850 855 860
Thr Thr Ala Leu Val Ile Ser Gly Ala Ser Trp Glu Thr Tyr Ala Asn
865 870 875 880
Ash Leu Ala Arg Gln Ala Leu Gln Val Arg Ala Gly Ser His Tyr Ala
885 890 895
Phe Ser Pro Met Phe Glu Val Leu Gly Gln Phe Val Phe Glu Val Arg
900 905 910
Gly Ser
(2)SEQ ID NO:27的信息:
(i)序列特征:
(A)长度:1200碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ix)特征:
(A)名称/关键字:编码序列
(B)位置:1...1200
(D)其它信息:
(xi)序列描述:SEQ ID NO:27:
GAT CCT AAA AAT AAA GAG TAC ACA GGG ACC ATA CTC TTT TCT GGA GAA 48
Asp Pro Lys Asn Lys Glu Tyr Thr Gly Thr Ile Leu Phe Ser Gly Glu
1 5 10 15
AAG AGT CTA GCA AAC GAT CCT AGG GAT TTT AAA TCT ACA ATC CCT CAG 96
Lys Ser Leu Ala Asn Asp Pro Arg Asp Phe Lys Ser Thr Ile Pro Gln
20 25 30
AAC GTC AAC CTG TCT GCA GGA TAC TTA GTT ATT AAA GAG GGG GCC GAA 144
Asn Val Asn Leu Ser Ala Gly Tyr Leu Val Ile Lys Glu Gly Ala Glu
35 40 45
GTC ACA GTT TCA AAA TTC ACG CAG TCT CCA GGA TCG CAT TTA GTT TTA 192
Val Thr Val Ser Lys Phe Thr Gln Ser Pro Gly Ser His Leu Val Leu
50 55 60
GAT TTA GGA ACC AAA CTG ATA GCC TCT AAG GAA GAC ATT GCC ATC ACA 240
Asp Leu Gly Thr Lys Leu Ile Ala Ser Lys Glu Asp Ile Ala Ile Thr
65 70 75 80
GGC CTC GCG ATA GAT ATA GAT AGC TTA AGC TCA TCC TCA ACA GCA GCT 288
Gly Leu Ala Ile Asp Ile Asp Ser Leu Ser Ser Ser Ser Thr Ala Ala
85 90 95
GTT ATT AAA GCA AAC ACC GCA AAT AAA CAG ATA TCC GTG ACG GAC TCT 336
Val Ile Lys Ala Asn Thr Ala Asn Lys Gln Ile Ser Val Thr Asp Ser
100 105 110
ATA GAA CTT ATC TCG CCT ACT GGC AAT GCC TAT GAA GAT CTC AGA ATG 384
Ile Glu Leu Ile Ser Pro Thr Gly Asn Ala Tyr Glu Asp Leu Arg Met
115 120 125
AGA AAT TCA CAG ACG TTC CCT CTG CTC TCT TTA GAG CCT GGA GCC GGG 432
Arg Asn Ser Gln Thr Phe Pro Leu Leu Ser Leu Glu Pro Gly Ala Gly
130 135 140
GGT AGT GTG ACT GTA ACT GCT GGA GAT TTC CTA CCG GTA AGT CCC CAT 480
Gly Ser Val Thr Val Thr Ala Gly Asp Phe Leu Pro Val Ser Pro His
145 150 155 160
TAT GGT TTT CAA GGC AAT TGG AAA TTA GCT TGG ACA GGA ACT GGA AAC 528
Tyr Gly Phe Gln Gly Asn Trp Lys Leu Ala Trp Thr Gly Thr Gly Asn
165 170 175
AAA GTT GGA GAA TTC TTC TGG GAT AAA ATA AAT TAT AAG CCT AGA CCT 576
Lys Val Gly Glu Phe Phe Trp Asp Lys Ile Asn Tyr Lys Pro Arg Pro
180 185 190
GAA AAA GAA GGA AAT TTA GTT CCT AAT ATC TTG TGG GGG AAT GCT GTA 624
Glu Lys Glu Gly Asn Leu Val Pro Asn Ile Leu Trp Gly Asn Ala Val
195 200 205
AAT GTC AGA TCC TTA ATG CAG GTT CAA GAG ACC CAT GCA TCG AGC TTA 672
Asn Val Arg Ser Leu Met Gln Val Gln Glu Thr His Ala Ser Ser Leu
210 215 220
CAG ACA GAT CGA GGG CTG TGG ATC GAT GGA ATT GGG AAT TTC TTC CAT 720
Gln Thr Asp Arg Gly Leu Trp Ile Asp Gly Ile Gly Asn Phe Phe His
225 230 235 240
GTA TCT GCC TCC GAA GAC AAT ATA AGG TAC CGT CAT AAC AGC GGT GGA 768
Val Ser Ala Ser Glu Asp Asn Ile Arg Tyr Arg His Asn Ser Gly Gly
245 250 255
TAT GTT CTA TCT GTA AAT AAT GAG ATC ACA CCT AAG CAC TAT ACT TCG 816
Tyr Val Leu Ser Val Asn Asn Glu Ile Thr Pro Lys His Tyr Thr Ser
260 265 270
ATG GCA TTT TCC CAA CTC TTT AGT AGA GAC AAA GAC TAT GCG GTT TCC 864
Met Ala Phe Ser Gln Leu Phe Ser Arg Asp Lys Asp Tyr Ala Val Ser
275 280 285
AAC AAC GAA TAC AGA ATG TAT TTA GGA TCG TAT CTC TAT CAA TAT ACA 912
Asn Asn Glu Tyr Arg Met Tyr Leu Gly Ser Tyr Leu Tyr Gln Tyr Thr
290 295 300
ACC TCC CTA GGG AAT ATT TTC CGT TAT GCT TCG CGT AAC CCT AAT GTA 960
Thr Ser Leu Gly Asn Ile Phe Arg Tyr Ala Ser Arg Asn Pro Asn Val
305 310 315 320
AAC GTC GGG ATT CTC TCA AGA AGG TTT CTT CAA AAT CCT CTT ATG ATT 1008
Asn Val Gly Ile Leu Ser Arg Arg Phe Leu Gln Asn Pro Leu Met Ile
325 330 335
TTT CAT TTT TTG TGT GCT TAT GGT CAT GCC ACC AAT GAT ATG AAA ACA 1056
Phe His Phe Leu Cys Ala Tyr Gly His Ala Thr Asn Asp Met Lys Thr
340 345 350
GAC TAC GCA AAT TTC CCT ATG GTG AAA AAC AGC TGG AGA AAC AAT TGT 1104
Asp Tyr Ala Asn Phe Pro Met Val Lys Asn Ser Trp Arg Asn Asn Cys
355 360 365
TGG GCT ATA AAA TGC GGA GGG AGC ATG CCT CTA TTG GTA TTT GAA AAC 1152
Trp Ala Ile Lys Cys Gly Gly Ser Met Pro Leu Leu Val Phe Glu Asn
370 375 380
GGA AAA CTT TTC CAA GGT GCC ATC CCA TTT ATG AAA CTA CAA TTA GTT 1200
Gly Lys Leu Phe Gln Gly Ala Ile Pro Phe Met Lys Leu Gln Leu Val
385 390 395 400
(2)SEQ ID NO:28的信息:
(i)序列特征:
(A)长度:400氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白质
(v)片段类型:内部
(xi)序列描述:SEQ ID NO:28:
Asp Pro Lys Asn Lys Glu Tyr Thr Gly Thr Ile Leu Phe Ser Gly Glu
1 5 10 15
Lys Ser Leu Ala Asn Asp Pro Arg Asp Phe Lys Ser Thr Ile Pro Gln
20 25 30
Asn Val Asn Leu Ser Ala Gly Tyr Leu Val Ile Lys Glu Gly Ala Glu
35 40 45
Val Thr Val Ser Lys Phe Thr Gln Ser Pro Gly Ser His Leu Val Leu
50 55 60
Asp Leu Gly Thr Lys Leu Ile Ala Ser Lys Glu Asp Ile Ala Ile Thr
65 70 75 80
Gly Leu Ala Ile Asp Ile Asp Ser Leu Ser Ser Ser Ser Thr Ala Ala
85 90 95
Val Ile Lys Ala Asn Thr Ala Asn Lys Gln Ile Ser Val Thr Asp Ser
100 105 110
Ile Glu Leu Ile Ser Pro Thr Gly Asn Ala Tyr Glu Asp Leu Arg Met
115 120 125
Arg Asn Ser Gln Thr Phe Pro Leu Leu Ser Leu Glu Pro Gly Ala Gly
130 135 140
Gly Ser Val Thr Val Thr Ala Gly Asp Phe Leu Pro Val Ser Pro His
145 150 155 160
Tyr Gly Phe Gln Gly Asn Trp Lys Leu Ala Trp Thr Gly Thr Gly Asn
165 170 175
Lys Val Gly Glu Phe Phe Trp Asp Lys Ile Asn Tyr Lys Pro Arg Pro
180 185 190
Glu Lys Glu Gly Asn Leu Val Pro Asn Ile Leu Trp Gly Asn Ala Val
195 200 205
Asn Val Arg Ser Leu Met Gln Val Gln Glu Thr His Ala Ser Ser Leu
210 215 220
Gln Thr Asp Arg Gly Leu Trp Ile Asp Gly Ile Gly Asn Phe Phe His
225 230 235 240
Val Ser Ala Ser Glu Asp Asn Ile Arg Tyr Arg His Asn Ser Gly Gly
245 250 255
Tyr Val Leu Ser Val Asn Asn Glu Ile Thr Pro Lys His Tyr Thr Ser
260 265 270
Met Ala Phe Ser Gln Leu Phe Ser Arg Asp Lys Asp Tyr Ala Val Ser
275 280 285
Asn Asn Glu Tyr Arg Met Tyr Leu Gly Ser Tyr Leu Tyr Gln Tyr Thr
290 295 300
Thr Ser Leu Gly Asn Ile Phe Arg Tyr Ala Ser Arg Asn Pro Asn Val
305 310 315 320
Asn Val Gly Ile Leu Ser Arg Arg Phe Leu Gln Asn Pro Leu Met Ile
325 330 335
Phe His Phe Leu Cys Ala Tyr Gly His Ala Thr Asn Asp Met Lys Thr
340 345 350
Asp Tyr Ala Asn Phe Pro Met Val Lys Asn Ser Trp Arg Asn Asn Cys
355 360 365
Trp Ala Ile Lys Cys Gly Gly Ser Met Pro Leu Leu Val Phe Glu Asn
370 375 380
Gly Lys Leu Phe Gln Gly Ala Ile Pro Phe Met Lys Leu Gln Leu Val
385 390 395 400
(2)SEQ ID NO:29的信息:
(i)序列特征:
(A)长度:1830碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:cDNA
(ix)特征:
(A)名称/关键字:编码序列
(B)位置:1...1830
(D)其它信息:
(xi)序列描述:SEQ ID NO:29:
GAT CTC ACA TTA GGG AGT CGT GAC AGT TAT AAT GGT GAT ACA AGC ACC 48
Asp Leu Thr Leu Gly Ser Arg Asp Ser Tyr Asn Gly Asp Thr Ser Thr
1 5 10 15
ACA GAA TTT ACT CCT AAA GCG GCA ACT TCT GAT GCT AGT GGC ACG ACC 96
Thr Glu Phe Thr Pro Lys Ala Ala Thr Ser Asp Ala Ser Gly Thr Thr
20 25 30
TAT ATT CTC GAT GGG GAT GTC TCG ATA AGC CAA GCA GGG AAA CAA ACG 144
Tyr Ile Leu Asp Gly Asp Val Ser Ile Ser Gln Ala Gly Lys Gln Thr
35 40 45
AGC TTA ACC ACA AGT TGT TTT TCT AAC ACT GCA GGA AAT CTT ACC TTC 192
Ser Leu Thr Thr Ser Cys Phe Ser Asn Thr Ala Gly Asn Leu Thr Phe
50 55 60
TTA GGG AAC GGA TTT TCT CTT CAT TTT GAC AAT ATT ATT TCG TCT ACT 240
Leu Gly Asn Gly Phe Ser Leu His Phe Asp Asn Ile Ile Ser Ser Thr
65 70 75 80
GTT GCA GGT GTT GTT GTT AGC AAT ACA GCA GCT TCT GGG ATT ACG AAA 288
Val Ala Gly Val Val Val Ser Asn Thr Ala Ala Ser Gly Ile Thr Lys
85 90 95
TTC TCA GGA TTT TCA ACT CTT CGG ATG CTT GCA GCT CCT AGG ACC ACA 336
Phe Ser Gly Phe Ser Thr Leu Arg Met Leu Ala Ala Pro Arg Thr Thr
100 105 110
GGT AAA GGA GCC ATT AAA ATT ACC GAT GGT CTG GTG TTT GAG AGT ATA 384
Gly Lys Gly Ala Ile Lys Ile Thr Asp Gly Leu Val Phe Glu Ser Ile
115 120 125
GGG AAT CTT GAT CCG ATT ACT GTA ACA GGA TCG ACA TCT GTT GCT GAT 432
Gly Asn Leu Asp Pro Ile Thr Val Thr Gly Ser Thr Ser Val Ala Asp
130 135 140
GCT CTC AAT ATT AAT AGC CCT GAT ACT GGA GAT AAC AAA GAG TAT ACG 480
Ala Leu Asn Ile Asn Ser Pro Asp Thr Gly Asp Asn Lys Glu Tyr Thr
145 150 155 160
GGA ACC ATA GTC TTT TCT GGA GAG AAG CTC ACG GAG GCA GAA GCT AAA 528
Gly Thr Ile Val Phe Ser Gly Glu Lys Leu Thr Glu Ala Glu Ala Lys
165 170 175
GAT GAG AAG AAC CGC ACT TCT AAA TTA CTT CAA AAT GTT GCT TTT AAA 576
Asp Glu Lys Asn Arg Thr Ser Lys Leu Leu Gln Asn Val Ala Phe Lys
180 185 190
AAT GGG ACT GTA GTT TTA AAA GGT GAT GTC GTT TTA AGT GCG AAC GGT 624
Asn Gly Thr Val Val Leu Lys Gly Asp Val Val Leu Ser Ala Asn Gly
195 200 205
TTC TCT CAG GAT GCA AAC TCT AAG TTG ATT ATG GAT TTA GGG ACG TCG 672
Phe Ser Gln Asp Ala Asn Ser Lys Leu Ile Met Asp Leu Gly Thr Ser
210 215 220
TTG GTT GCA AAC ACC GAA AGT ATC GAG TTA ACG AAT TTG GAA ATT AAT 720
Leu Val Ala Asn Thr Glu Ser Ile Glu Leu Thr Asn Leu Glu Ile Asn
225 230 235 240
ATA GAC TCT CTC AGG AAC GGG AAA AAG ATA AAA CTC AGT GCT GCC ACA 768
Ile Asp Ser Leu Arg Asn Gly Lys Lys Ile Lys Leu Ser Ala Ala Thr
245 250 255
GCT CAG AAA GAT ATT CGT ATA GAT CGT CCT GTT GTA CTG GCA ATT AGC 816
Ala Gln Lys Asp Ile Arg Ile Asp Arg Pro Val Val Leu Ala Ile Ser
260 265 270
GAT GAG AGT TTT TAT CAA AAT GGC TTT TTG AAT GAG GAC CAT TCC TAT 864
Asp Glu Ser Phe Tyr Gln Asn Gly Phe Leu Asn Glu Asp His Ser Tyr
275 280 285
GAT GGG ATT CTT GAG TTA GAT GCT GGG AAA GAC ATC GTG ATT TCT GCA 912
Asp Gly Ile Leu Glu Leu Asp Ala Gly Lys Asp Ile Val Ile Ser Ala
290 295 300
GAT TCT CGC AGT ATA GAT GCT GTA CAA TCT CCG TAT GGC TAT CAG GGA 960
Asp Ser Arg Ser Ile Asp Ala Val Gln Ser Pro Tyr Gly Tyr Gln Gly
305 310 315 320
AAG TGG ACG ATC AAT TGG TCT ACT GAT GAT AAG AAA GCT ACG GTT TCT 1008
Lys Trp Thr Ile Asn Trp Ser Thr Asp Asp Lys Lys Ala Thr Val Ser
325 330 335
TGG GCG AAG CAG AGT TTT AAT CCC ACT GCT GAG CAG GAG GCT CCG TTA 1056
Trp Ala Lys Gln Ser Phe Asn Pro Thr Ala Glu Gln Glu Ala Pro Leu
340 345 350
GTT CCT AAT CTT CTT TGG GGT TCT TTT ATA GAT GTT CGT TCC TTC CAG 1104
Val Pro Asn Leu Leu Trp Gly Ser Phe Ile Asp Val Arg Ser Phe Gln
355 360 365
AAT TTT ATA GAG CTA GGT ACT GAA GGT GCT CCT TAC GAA AAG AGA TTT 1152
Asn Phe Ile Glu Leu Gly Thr Glu Gly Ala Pro Tyr Glu Lys Arg Phe
370 375 380
TGG GTT GCA GGC ATT TCC AAT GTT TTG CAT AGG AGC GGT CGT GAA AAT 1200
Trp Val Ala Gly Ile Ser Asn Val Leu His Arg Ser Gly Arg Glu Asn
385 390 395 400
CAA AGG AAA TTC CGT CAT GTG AGT GGA GGT GCT GTA GTA GGT GCT AGC 1248
Gln Arg Lys Phe Arg His Val Ser Gly Gly Ala Val Val Gly Ala Ser
405 410 415
ACG AGG ATG CCG GGT GGT GAT ACC TTG TCT CTG GGT TTT GCT CAG CTC 1296
Thr Arg Met Pro Gly Gly Asp Thr Leu Ser Leu Gly Phe Ala Gln Leu
420 425 430
TTT GCG CGT GAC AAA GAC TAC TTT ATG AAT ACC AAT TTC GCA AAG ACC 1344
Phe Ala Arg Asp Lys Asp Tyr Phe Met Asn Thr Asn Phe Ala Lys Thr
435 440 445
TAC GCA GGA TCT TTA CGT TTG CAG CAC GAT GCT TCC CTA TAC TCT GTG 1392
Tyr Ala Gly Ser Leu Arg Leu Gln His Asp Ala Ser Leu Tyr Ser Val
450 455 460
GTG AGT ATC CTT TTA GGA GAG GGA GGA CTC CGC GAG ATC CTG TTG CCT 1440
Val Ser Ile Leu Leu Gly Glu Gly Gly Leu Arg Glu Ile Leu Leu Pro
465 470 475 480
TAT GTT TCC AAT ACT CTG CCG TGC TCT TTC TAT GGG CAG CTT AGC TAC 1488
Tyr Val Ser Asn Thr Leu Pro Cys Ser Phe Tyr Gly Gln Leu Ser Tyr
485 490 495
GGC CAT ACG GAT CAT CGC ATG AAG ACC GAG TCT CTA CCC CCC CCC CCC 1536
Gly His Thr Asp His Arg Met Lys Thr Glu Ser Leu Pro Pro Pro Pro
500 505 510
CCG ACG CTC TCG ACG GAT CAT ACT TCT TGG GGA GGA TAT GTC TGG GCT 1584
Pro Thr Leu Ser Thr Asp His Thr Ser Trp Gly Gly Tyr Val Trp Ala
515 520 525
GGA GAG CTG GGA ACT CGA GTT GCT GTT GAA AAT ACC AGC GGC AGA GGA 1632
Gly Glu Leu Gly Thr Arg Val Ala Val Glu Asn Thr Ser Gly Arg Gly
530 535 540
TTT TTC CGA GAG TAC ACT CCA TTT GTA AAA GTC CAA GCT GTT TAC TCG 1680
Phe Phe Arg Glu Tyr Thr Pro Phe Val Lys Val Gln Ala Val Tyr Ser
545 550 555 560
CGC CAA GAT AGC TTT GTT GAA CTA GGA GCT ATC AGT CGT GAT TTT AGT 1728
Arg Gln Asp Ser Phe Val Glu Leu Gly Ala Ile Ser Arg Asp Phe Ser
565 570 575
GAT TCG CAT CTT TAT AAC CTT GCG ATT CCT CTT GGA ATC AAG TTA GAG 1776
Asp Ser His Leu Tyr Asn Leu Ala Ile Pro Leu Gly Ile Lys Leu Glu
580 585 590
AAA CGG TTT GCA GAG CAA TAT TAT CAT GTT GTT GCG ATG TAT TCT CCA 1824
Lys Arg Phe Ala Glu Gln Tyr Tyr His Val ValAla Met Tyr Ser Pro
595 600 605
GAT GTT 1830
Asp Val
610
(2)SEQ ID NO:30的信息:
(i)序列特征:
(A)长度:610氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑结构:线性
(ii)分子类型:蛋白质
(v)片段类型:内部
(xi)序列描述:SEQ ID NO:30:
Asp Leu Thr Leu Gly Ser Arg Asp Ser Tyr Asn Gly Asp Thr Ser Thr
1 5 10 15
Thr Glu Phe Thr Pro Lys Ala Ala Thr Ser Asp Ala Ser Gly Thr Thr
20 25 30
Tyr Ile Leu Asp Gly Asp Val Ser Ile Ser Gln Ala Gly Lys Gln Thr
35 40 45
Ser Leu Thr Thr Ser Cys Phe Ser Asn Thr Ala Gly Asn Leu Thr Phe
50 55 60
Leu Gly Asn Gly Phe Ser Leu His Phe Asp Asn Ile Ile Ser Ser Thr
65 70 75 80
Val Ala Gly Val Val Val Ser Ash Thr Ala Ala Ser Gly Ile Thr Lys
85 90 95
Phe Ser Gly Phe Ser Thr Leu Arg Met Leu Ala Ala Pro Arg Thr Thr
100 105 110
Gly Lys Gly Ala Ile Lys Ile Thr Asp Gly Leu Val Phe Glu Ser Ile
115 120 125
Gly Asn Leu Asp Pro Ile Thr Val Thr Gly Ser Thr Ser Val Ala Asp
130 135 140
Ala Leu Asn Ile Asn Ser Pro Asp Thr Gly Asp Asn Lys Glu Tyr Thr
145 150 155 160
Gly Thr Ile Val Phe Ser Gly Glu Lys Leu Thr Glu Ala Glu Ala Lys
165 170 175
Asp Glu Lys Asn Arg Thr Ser Lys Leu Leu Gln Asn Val Ala Phe Lys
180 185 190
Asn Gly Thr Val Val Leu Lys Gly Asp Val Val Leu Ser Ala Asn Gly
195 200 205
Phe Ser Gln Asp Ala Asn Ser Lys Leu Ile Met Asp Leu Gly Thr Ser
210 215 220
Leu Val Ala Asn Thr Glu Ser Ile Glu Leu Thr Asn Leu Glu Ile Asn
225 230 235 240
Ile Asp Ser Leu Arg Asn Gly Lys Lys Ile Lys Leu Ser Ala Ala Thr
245 250 255
Ala Gln Lys Asp Ile Arg Ile Asp Arg Pro Val Val Leu Ala Ile Ser
260 265 270
Asp Glu Ser Phe Tyr Gln Asn Gly Phe Leu Asn Glu Asp His Ser Tyr
275 280 285
Asp Gly Ile Leu Glu Leu Asp Ala Gly Lys Asp Ile Val Ile Ser Ala
290 295 300
Asp Ser Arg Ser Ile Asp Ala Val Gln Ser Pro Tyr Gly Tyr Gln Gly
305 310 315 320
Lys Trp Thr Ile Asn Trp Ser Thr Asp Asp Lys Lys Ala Thr Val Ser
325 330 335
Trp Ala Lys Gln Ser Phe Asn Pro Thr Ala Glu Gln Glu Ala Pro Leu
340 345 350
Val Pro Asn Leu Leu Trp Gly Ser Phe Ile Asp Val Arg Ser Phe Gln
355 360 365
Asn Phe Ile Glu Leu Gly Thr Glu Gly Ala Pro Tyr Glu Lys Arg Phe
370 375 380
Trp Val Ala Gly Ile Ser Asn Val Leu His Arg Ser Gly Arg Glu Asn
385 390 395 400
Gln Arg Lys Phe Arg His Val Ser Gly Gly Ala Val Val Gly Ala Ser
405 410 415
Thr Arg Met Pro Gly Gly Asp Thr Leu Ser Leu Gly Phe Ala Gln Leu
420 425 430
Phe Ala Arg Asp Lys Asp Tyr Phe Met Asn Thr Asn Phe Ala Lys Thr
435 440 445
Tyr Ala Gly Ser Leu Arg Leu Gln His Asp Ala Ser Leu Tyr Ser Val
450 455 460
Val Ser Ile Leu Leu Gly Glu Gly Gly Leu Arg Glu Ile Leu Leu Pro
465 470 475 480
Tyr Val Ser Asn Thr Leu Pro Cys Ser Phe Tyr Gly Gln Leu Ser Tyr
485 490 495
Gly His Thr Asp His Arg Met Lys Thr Glu Ser Leu Pro Pro Pro Pro
500 505 510
Pro Thr Leu Ser Thr Asp His Thr Ser Trp Gly Gly Tyr Val Trp Ala
515 520 525
Gly Glu Leu Gly Thr Arg Val Ala Val Glu Asn Thr Ser Gly Arg Gly
530 535 540
Phe Phe Arg Glu Tyr Thr Pro Phe Val Lys Val Gln Ala Val Tyr Ser
545 550 555 560
Arg Gln Asp Ser Phe Val Glu Leu Gly Ala Ile Ser Arg Asp Phe Ser
565 570 575
Asp Ser His Leu Tyr Asn Leu Ala Ile Pro Leu Gly Ile Lys Leu Glu
580 585 590
Lys Arg Phe Ala Glu Gln Tyr Tyr His Val Val Ala Met Tyr Ser Pro
595 600 605
Asp Val
610
Claims (15)
1.一种鉴定哺乳动物感染肺炎衣原体的种特异性测试方法,所述测试方法包括:检测患者样品内是否有针对肺炎衣原体外膜的一种或多种蛋白的抗体存在,所述蛋白是外膜蛋白,选自具有SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22或SEQ ID NO:24所示序列或它的变体或亚序列,所述变体或亚序列与所述外膜蛋白有至少80%同源性并具有相同生物功能,
或所述蛋白由选自具有SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:21或SEQ ID NO:23所示核苷酸序列的核酸片段或所述核酸片段的变体或亚序列所编码,所述核酸片段的变体或亚序列与所述核酸片段有至少80%同源性并且编码具有相同生物功能的蛋白质。
2.根据权利要求1所述的测试方法,其中用核酸扩增检测核酸片段。
3.根据权利要求2所述的测试方法,其中用聚合酶链反应检测核酸片段。
4.一种衍生自肺炎衣原体的核酸片段,它包含SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:21或SEQ ID NO:23所示的核苷酸序列,或所述核苷酸序列的变体或亚序列,所述核苷酸片段的变体或亚序列与所述核苷酸序列有至少80%同源性并且编码具有相同生物功能的蛋白质。
5.一种衍生自肺炎衣原体的具有SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22或SEQ ID NO:24所示氨基酸序列的蛋白质或与所述蛋白质有至少80%同源性并具有相同生物功能的所述蛋白质的变体或亚序列。
6.一种多克隆单特异性抗体,它针对具有SEQ ID NO:2、SEQ ID NO:4、SEQ IDNO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22或SEQ ID NO:24所示序列的蛋白质或所述蛋白质的变体或亚序列,所述蛋白质的变体或亚序列与所述蛋白质有至少80%同源性并具有相同生物功能。
7.一种用来诊断哺乳动物感染肺炎衣原体的诊断试剂盒,所述试剂盒包含具有SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQID NO:22或SEQ ID NO:24所示氨基酸序列的蛋白质或所述蛋白质的变体或亚序列,所述蛋白质的变体或亚序列与所述蛋白质有至少80%同源性并具有相同生物功能。
8.一种用来诊断哺乳动物感染肺炎衣原体的诊断试剂盒,所述试剂盒包含抗体,该抗体针对具有SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQID NO:20、SEQ ID NO:22或SEQ ID NO:24所示氨基酸序列的蛋白质或所述蛋白质的变体或亚序列,所述蛋白质的变体或亚序列与所述蛋白质有至少80%同源性并具有相同生物功能。
9.一种用来诊断哺乳动物感染肺炎衣原体的诊断试剂盒,所述试剂盒包含具有SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:9、SEQ IDNO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ IDNO:21或SEQ ID NO:23所示序列的核酸片段或所述核酸片段的变体或亚序列,所述核酸片段的变体或亚序列与所述核酸片段有至少80%同源性并且编码具有相同生物功能的蛋白质。
10.一种用来免疫接种哺乳动物来抵抗肺炎衣原体的组合物,所述组合物包含具有SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22或SEQ ID NO:24所示氨基酸序列的蛋白质或所述蛋白质的变体或亚序列,所述蛋白质的变体或亚序列与所述蛋白质有至少80%同源性并具有相同生物功能。
11.具有SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ IDNO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ IDNO:20、SEQ ID NO:22或SEQ ID NO:24所示序列的蛋白质或与所述蛋白质有至少80%同源性并具有相同生物功能的所述蛋白质的变体或亚序列在制备用于诊断哺乳动物感染肺炎衣原体的药物中的用途。
12.非变性形式的具有SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22或SEQ ID NO:24所示序列的蛋白质或与所述蛋白质有至少80%同源性并具有相同生物功能的所述蛋白质的变体或亚序列在制备用于诊断哺乳动物感染肺炎衣原体的药物中的用途。
13.具有SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ IDNO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ IDNO:20、SEQ ID NO:22或SEQ ID NO:24所示序列的蛋白质或与所述蛋白质有至少80%同源性并具有相同生物功能的所述蛋白质的变体或亚序列在制备免疫接种哺乳动物以抵抗肺炎衣原体的药物中的应用。
14.非变性形式的具有SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22或SEQ ID NO:24所示序列的蛋白质或与所述蛋白质有至少80%同源性并具有相同生物功能的所述蛋白质的变体或亚序列在制备免疫接种哺乳动物以抵抗肺炎衣原体的药物中的应用。
15.具有SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:7、SEQ IDNO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:21或SEQ ID NO:23所示核苷酸序列的核酸片段或与所述核酸片段有至少80%同源性并且编码具有相同生物功能的蛋白质的所述核酸片段的变体或亚序列在制备在哺乳动物中实现体内表达抗原以抵抗肺炎衣原体的药物中的应用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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DK0744/1997 | 1997-06-23 | ||
DK74497 | 1997-06-23 | ||
DK0744/97 | 1997-06-23 |
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CN1261403A CN1261403A (zh) | 2000-07-26 |
CN1249233C true CN1249233C (zh) | 2006-04-05 |
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CNB988064286A Expired - Fee Related CN1249233C (zh) | 1997-06-23 | 1998-06-19 | 肺炎衣原体表面蛋白 |
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US (2) | US7264941B1 (zh) |
EP (1) | EP1007685B1 (zh) |
JP (1) | JP4160640B2 (zh) |
CN (1) | CN1249233C (zh) |
AT (1) | ATE323164T1 (zh) |
AU (1) | AU749382B2 (zh) |
BR (1) | BR9810288A (zh) |
CA (1) | CA2294651A1 (zh) |
DE (1) | DE69834194T2 (zh) |
DK (1) | DK1007685T3 (zh) |
ES (1) | ES2264810T3 (zh) |
PT (1) | PT1007685E (zh) |
WO (1) | WO1998058953A2 (zh) |
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US6710033B1 (en) | 1996-08-14 | 2004-03-23 | Vanderbilt University | Methods and treatment of multiple sclerosis |
US6890526B2 (en) | 1997-05-06 | 2005-05-10 | Vanderbilt University | Methods and reagents for the treatment of multiple sclerosis |
EP1129202A2 (en) * | 1998-10-28 | 2001-09-05 | Aventis Pasteur Limited | Chlamydia antigenes and corresponding dna fragments and uses thereof |
US6649370B1 (en) * | 1998-10-28 | 2003-11-18 | Aventis Pasteur Limited | Chlamydia antigens and corresponding DNA fragments and uses thereof |
US6872814B2 (en) * | 1998-10-29 | 2005-03-29 | Aventis Pasteur Limited | Chlamydia antigens and corresponding DNA fragments and uses thereof |
CA2352759A1 (en) * | 1998-12-01 | 2000-06-08 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
US20020094340A1 (en) * | 1998-12-01 | 2002-07-18 | Andrew D. Murdin | Chlamydia antigens and corresponding dna thereof |
EP2172214A3 (en) | 1999-03-12 | 2011-03-16 | Aventis Pasteur Limited | Chlamydia antigens and corresponding DNA fragments and uses thereof |
WO2000066739A2 (en) * | 1999-05-03 | 2000-11-09 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
JP4667694B2 (ja) | 1999-09-20 | 2011-04-13 | サノフィ、パストゥール、リミテッド | クラミジア抗原および対応するdna断片ならびにその使用 |
US20010048927A1 (en) | 2000-02-01 | 2001-12-06 | Richard Stephens | Porin B (PorB) as a therapeutic target for prevention and treatment of infection by chlamydia |
AU2001276619A1 (en) * | 2000-07-03 | 2002-01-14 | Chiron S.P.A. | Immunisation against chlamydia pneumoniae |
US7105171B2 (en) | 2002-03-07 | 2006-09-12 | The Regents Of The University Of California | Porin B (PorB) as a therapeutic target for prevention and treatment of infection by Chlamydia |
AU2017261283B2 (en) * | 2016-05-04 | 2023-02-09 | Children's Hospital & Research Center At Oakland | Rapid extraction of nucleic acids from clinical samples for downstream applications |
JP2022532050A (ja) * | 2019-05-06 | 2022-07-13 | アロセル エービー | 呼吸器感染の検出および分類 |
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AU692889B2 (en) * | 1994-08-03 | 1998-06-18 | Hitachi Chemical Company, Ltd. | Monoclonal antibodies having a reactivity specific to Chlamydia pneumoniae, method for production of the monoclonal antibodies, such antibody producing cells, method for production of the cells, method for detection and/or measurement of Chlamydia pneumoniae, reagents for the method, method and agents for diagnosis of chlamydia pneumoniae infection |
EP0784059B1 (en) | 1994-09-20 | 2009-02-11 | Hitachi Chemical Co., Ltd. | Polynucleotides encoding an antigenic polypeptide of chlamydia pneumoniae |
US6248329B1 (en) * | 1998-06-01 | 2001-06-19 | Ramaswamy Chandrashekar | Parasitic helminth cuticlin nucleic acid molecules and uses thereof |
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1998
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- 1998-06-19 CN CNB988064286A patent/CN1249233C/zh not_active Expired - Fee Related
- 1998-06-19 BR BR9810288-5A patent/BR9810288A/pt not_active Application Discontinuation
- 1998-06-19 CA CA002294651A patent/CA2294651A1/en not_active Abandoned
- 1998-06-19 AU AU80119/98A patent/AU749382B2/en not_active Ceased
- 1998-06-19 WO PCT/DK1998/000266 patent/WO1998058953A2/en active IP Right Grant
- 1998-06-19 EP EP98928179A patent/EP1007685B1/en not_active Expired - Lifetime
- 1998-06-19 JP JP50361399A patent/JP4160640B2/ja not_active Expired - Fee Related
- 1998-06-19 US US09/446,677 patent/US7264941B1/en not_active Expired - Fee Related
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- 1998-06-19 PT PT98928179T patent/PT1007685E/pt unknown
- 1998-06-19 AT AT98928179T patent/ATE323164T1/de not_active IP Right Cessation
- 1998-06-19 ES ES98928179T patent/ES2264810T3/es not_active Expired - Lifetime
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2007
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Also Published As
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US20080226679A1 (en) | 2008-09-18 |
PT1007685E (pt) | 2006-08-31 |
WO1998058953A3 (en) | 1999-03-18 |
CA2294651A1 (en) | 1998-12-30 |
US7264941B1 (en) | 2007-09-04 |
AU749382B2 (en) | 2002-06-27 |
DK1007685T3 (da) | 2006-08-14 |
EP1007685B1 (en) | 2006-04-12 |
EP1007685A2 (en) | 2000-06-14 |
CN1261403A (zh) | 2000-07-26 |
DE69834194D1 (de) | 2006-05-24 |
BR9810288A (pt) | 2000-09-19 |
AU8011998A (en) | 1999-01-04 |
ATE323164T1 (de) | 2006-04-15 |
WO1998058953A2 (en) | 1998-12-30 |
DE69834194T2 (de) | 2007-03-29 |
JP2002510970A (ja) | 2002-04-09 |
JP4160640B2 (ja) | 2008-10-01 |
ES2264810T3 (es) | 2007-01-16 |
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