毒力基因和蛋白质及其用途的制作方法

专利名称：毒力基因和蛋白质及其用途的制作方法
技术领域：
本发明涉及毒力基因和蛋白质的鉴定及其用途。更具体地说，本发明涉及它们在治疗和筛选药物中的用途。
背景技术：
大肠杆菌属于肠杆菌科或肠道细菌，它们是聚居在动物肠道中的革兰氏阴性微生物。该细菌科中的其它细菌包括肠杆菌属、克雷伯氏菌属、沙门氏菌属、志贺氏菌属和耶尔森氏菌属。尽管通常在人胃肠道中发现大肠杆菌，但是它与包括败血病、脑膜炎、尿道感染、伤口感染、脓肿形成、腹膜炎和胆管炎在内的人体疾病有关。
由大肠杆菌导致的疾病取决于某些毒力决定簇。例如，大肠杆菌与新生儿脑膜炎有关并已将主要的毒力决定簇鉴定为K1抗原，它是唾液酸的均聚物。K1抗原可以在回避宿主免疫系统和防止吞噬作用方面起作用。
发明概要本发明以一系列大肠杆菌K1中的毒力基因的鉴定以及相关的生物体为基础，其产物可能与生物体的致病性有关。
本发明的一个方面是一种由操纵子编码的肽、或其在革兰氏阴性菌中的同源物或其功能片段，其中所述的操纵子包括来自大肠杆菌K1的本文鉴定为mdoG、creC、recG、yggN、tatA、tatB、tatC、tatE、eck1、iroD、iroC、iroE、mtd2和ms1-16在内的任意基因。例如，这类肽在分离时适合于治疗用途。
本文所用的术语“功能片段”指的是保留与完整基因或肽类似的治疗用途的一部分基因或肽。例如，可以将所述肽的功能片段用作在疫苗或生产抗体过程中有用的抗原决定簇。可以将基因片段用于编码活性肽。另一方面，该基因片段可能在基因疗法中有用，从而靶向体内的野生型基因以便发挥治疗作用。
本发明的肽可以包括本文鉴定为SEQ ID NOS.2、5、7、9、11、12、13、14、16、23、24、25、26、28、31、29、32和35-48的任意氨基酸序列。
将这些肽类鉴定为毒力决定簇使得能够将它们以许多方式用于治疗感染。例如，可以将宿主转化以表达本发明的肽或将所述宿主进行修饰以便破坏编码所述肽的基因的表达。一种疫苗还可以包括用于治疗感染的本发明的肽或用于其表达的工具。此外，疫苗可以包括具有毒力基因缺失的微生物，其中所述的基因编码本发明的肽。
根据本发明的另一个方面，可以将所述肽类或基因用于筛选有潜能的抗微生物药或用于检测毒性。
本发明的另一个方面是本文所鉴定的任意产物在治疗或预防与革兰氏阴性菌、特别是大肠杆菌导致的感染有关的疾病中的用途。
发明描述本发明利用了特征标记的诱变(STM)(Hensel等《科学》(Science)1995；269400-403)以便筛选减毒突变体的大肠杆菌K1菌株RS228(Pluschke等《感染与免疫》(Infection and Immunity)39599-608)小Tn5突变体库，从而鉴定了大肠杆菌的毒力基因(和毒力决定簇)。
尽管将大肠杆菌K1用作鉴定毒力基因的微生物，但是也将其它肠道细菌中的相应基因看作属于本发明的范围。例如，以序列同源性为基础，可以在肠杆菌属、克雷伯氏菌属和包括沙门氏菌属、志贺氏菌属和耶尔森氏菌属在内的与人体肠道疾病相关的其它属中发现相应的基因或编码的蛋白质。
本文所用的术语“毒力决定簇”指的是一种产物，例如一种可能起维持病原菌作用的肽或蛋白质。特别地，毒力决定簇是一种与感染性或导致疾病的微生物有关的细菌蛋白质或肽。
可以将编码毒力决定簇的基因称作“毒力基因”。通过突变、缺失或插入破坏毒力基因会导致细菌在宿主中的存活率降低或通常导致微生物致病性的降低。
已经证实特征标记的诱变是一种用于鉴定毒力基因及其产物的极为有用的技术。该项技术依赖于转座子在允许条件下随机插入微生物基因组中的能力。将转座子分别标记以便于鉴定且然后分别引入微生物，从而使基因组受到破坏。接着通过阴性选择来检测毒力降低的突变型微生物并对已经发生插入失活的基因进行鉴定和特征记述。
STM过程中的第一个阶段是制备合适的转座子或转座子样元件。制备不同转座子文库，将它们各自引入载体或质粒以促进其转入微生物。本领域技术人员显然可以制备带有合适转座子的载体且这项技术进一步公开在WO-A-96/17951中。对于革兰氏阴性菌例如大肠杆菌来说，合适的转座子包括Tn5和Tn10。在制备了转座子后，则对细菌菌株进行诱变以便建立各突变型细菌的文库。
接着将收集的突变型微生物引入合适的宿主。在适当长的时间后，从宿主中回收微生物并鉴定已经在宿主中存活的那些微生物，由此还鉴定了不能存活的突变型菌株即减毒株。然后将储存文库中相应的减毒株用于鉴定发生插入失活的基因。通常，通过分离位于转座子插入位点侧翼的DNA来鉴定转座子插入的位点且这使得对与毒力相关的基因进行特征记述成为可能。
一旦鉴定了无毒性微生物，则能够通过用致死剂量的突变体感染合适的宿主动物而更充分地确定突变型基因在毒力中的潜在作用。将受感染动物的存活时间与用野生型菌株感染的对照组动物的存活时间进行比较且一般可以认为存活期限比对照组动物长的那些动物感染了带有突变型毒力基因的微生物。
另一方面，通过用野生型和突变体细菌的混合物感染动物宿主可以研究毒力中的潜在作用。在合适的时间期限后，从宿主动物的器官中收集细菌并测定野生型和突变体细菌的比例。将该比例除以接种物中突变体与野生型细菌的比例来确定竞争指数(CI)。可以认为具有竞争指数小于1的突变体是无毒性的。
有可能通过插入转座子而失活的基因可能不是真正的毒力基因，但是可以对下游(毒力)基因具有极性作用。这可以通过进一步的实验来确定，所述的实验过程包括使非极性突变置于基因的更为确定的区域或使其它邻近基因发生突变并确定该突变体是否是无毒性的。
由于对大肠杆菌中的毒力基因进行了特征记述，所以有可能使用用来确定其它微生物中同源性的基因序列。以这种方式，有可能确定其它微生物是否具有相似的毒力决定簇。通过检索例如EMBL或Genbank这样的现存的数据库可以确定序列同源性。
通常使毒力基因在称作致病性岛的不同染色体区中彼此群集。当致病性岛通常位于重复序列、插入元件或tRNA基因侧翼时，可以识别它们。另外，G+C含量一般不同于染色体的剩余物，这提示它们通过从另一种生物体中的水平传递而获得。例如，大肠杆菌K12的G+C含量为52％。在大肠杆菌菌株中发现的任意致病性岛可能具有不同于该平均值的G+C含量。
经鉴定的毒力基因能够用于生产减毒的疫苗菌株和作为抗微生物药的靶物。一般来说，这对于革兰氏阴性菌中的同源物来说同样确切。
为了本发明的目的，同源性的适当程度一般至少为30％，优选至少为50％、60％或70％，且更优选至少为80％或90％(在氨基酸或核苷酸水平上)。
通过本领域中已知的方法可以纯化和分离本发明的蛋白质。特别地，由于鉴定了基因序列，所以有可能使用重组技术在合适的宿主中表达基因。可以鉴定活性片段和同源物并可以将它们用于治疗中。例如，可以将蛋白质或其活性片段用作疫苗中的抗原决定簇以便引起免疫反应。还可以将它们用于制备被动免疫用抗体或用于诊断应用。合适的抗体包括单克隆抗体或包括单链fv片段在内的其片段。抗体的制备方法对于本领域技术人员来说是显而易见的。
以减毒微生物为基础的疫苗制品对本领域技术人员来说是已知的。如果必要或需要，可以用例如明矾这样的合适的载体或佐剂来配制疫苗组合物并可以将它们用于治疗，从而提供对大肠杆菌或其它革兰氏阴性菌的有效免疫接种。疫苗制品的制备方法对于本领域技术人员来说是显而易见的。
更为常见的和正如本领域技术人员众所周知的，当可以含有合适的载体或赋形剂时，可以对本发明活性成分的治疗用合适量和给药途径进行选择。根据诸如所治疗疾病的性质/严重程度、患者的类型或健康情况等这样的已知标准来选择或决定这些因素。
下列实施例解释了本发明。对于这些实施例来说，使用全身感染的小鼠模型将STM用于筛选减毒突变体的大肠杆菌K1小Tn5突变体库。该实验方法的基本步骤公开在Hensel等的上述文献中。未从接种了混合型突变体群体的小鼠中回收到毒力基因内含有小Tn5插入物的大肠杆菌K1且因此该大肠杆菌K1可能是被减毒的。
通过反向PCR或通过拯救卡那霉素抗性标记克隆了位于小Tn5插入物各侧翼的DNA区。在后一种情况下，将来自STM衍生的突变体的染色体DNA用限制酶消化、连入质粒pUC19并在转化入感受态大肠杆菌K12细胞后选择卡那霉素抗性克隆。然后进行随后的克隆和测序步骤并使用可公开得到的序列数据库(EMBL)中的序列与所述基因序列进行比较以便辅助进行对推定基因产物的特征记述。
实施例1在第一种突变体中，对所克隆的DNA的两个片段进行测序。将核苷酸序列表示为SEQ ID NO.1和SEQ ID NO.3并将来自SEQ ID NO.1的DNA翻译区表示为SEQ ID NO.2。SEQ ID NO.1显示出与来自大肠杆菌K12(EMBL数据库登记号AE000206)的mdoGH区的2577-6908位核苷酸具有99.8％的同一性。这种DNA片段编码ymdD基因的5’部分、完整的mdoG基因和mdoH基因的5’部分。mdoG基因产物的功能是未知的，不过，认为它与膜衍生的寡糖类的生物合成有关。
SEQ ID NO.3显示出与来自大肠杆菌K12的mdoGH基因的3’部分和下游基因序列(7187-7760位核苷酸)具有98.3％的同一性。SEQID NO.2显示出与来自大肠杆菌K12(Swiss Prot登记号P33136)的mdoG蛋白质在1-511位氨基酸上具有99.6％的同一性。
在全身感染的小鼠模型体内测试新型基因对使用混合型感染的毒力的减毒作用(Achtman等《感染与免疫》(Infection and Immunity)1983；第39卷315-335)并证实以0.38的竞争指数被减毒。这证实原始转座子突变体的减毒可能是因mdoG基因受到破坏而导致的。
构建mdoG的极性和非极性缺失突变体。通过使用寡核苷酸5’-TGCTCTAGAGCCATTACTCAGAATGGG-3’(SEQ ID NO.49)和5’-CGCGAGCTCGACGACTGAATGATCCC-3’(SEQ ID NO.50)进行PCR来扩增mdoG基因和侧翼区。将产物克隆入pUC19。然后通过使用寡核苷酸5’-TCCCCCGGGTACTGCAGCACTCAACC-3’(SEQ ID NO.51)和5’-GATCCCGGGACCACTGAAATGCGTGC-3’(SEQ ID NO.52)进行反向PCR来扩增含有mdoG的5’-和3’-末端片段和完整pUC19序列的PCR产物。将非极性卡那霉素抗性弹夹(aphT)沿两个方向插入mdoG序列之间而得到极性和非极性构建体。接着将mdoG::aphT融合体转入自杀载体pCDV442。通过将pCDV442构建体连入野生型大肠杆菌K1后的等位转移使mdoG的染色体拷贝发生突变。
测试所构建的突变体在全身感染小鼠模型体内对毒力的减毒作用(Achtman等，文献同上)。分别以0.37和0.35的竞争指数(平均值C1来自三只小鼠)使极性和非极性构建体的毒力得到弱化。这证明原始转座子突变体的减毒可能是因mdoG基因受到破坏而导致的。
实施例2用具有SEQ ID NO.4表示的核苷酸序列和表示为SEQ ID NO.5的翻译的氨基酸序列的毒力基因鉴定第二种突变体。小Tn5转座子插在581位核苷酸(SEQ ID NO.4)和187位氨基酸(SEQ ID NO.5)上。
这些序列显示出与大肠杆菌K12(EMBL和Genbank登记号M13608、AE000510和U14003)的creC基因具有97.9％的同一性。
来自大肠杆菌K12的creC蛋白质属于组氨酸激酶的蛋白质族且属于由含信号结构域的蛋白质组成的蛋白质族。
测试新型基因对毒力的减毒作用(Achtman等，文献同上)且证实该新型基因是以0.09的竞争指数被减毒的。
当将大肠杆菌K12 creC基因转录成带有creD基因的操纵子的一部分时，这种减毒作用可能是因对推定大肠杆菌K1 creD基因的极性作用所导致的。
实施例3第三种突变体在紧接小Tn5后带有表示为SEQ ID NO.6的核苷酸序列。将翻译的该序列表示为SEQ ID NO.7。
该核苷酸序列显示出与大肠杆菌K12(EMBL和Genbank登记号P24230和M64367)recG基因的5-146位核苷酸具有93.7％的同一性。这表明受到破坏的基因至少部分与大肠杆菌K12的recG基因相同。大肠杆菌K12的recG基因编码起ATP依赖性DNA解旋酶作用的76.4kD蛋白质并在DNA修复过程中起关键作用。
在减毒试验中，证实竞争指数为0.48。将recG基因转录成操纵子的末端基因且因此由于对另一种大肠杆菌K1基因产生极性作用而导致这种减毒作用是不可能的。
实施例4如果翻译产物表示为SEQ ID NO.9，那么第四种突变体带有在表示为SEQ ID NO.8的核苷酸序列内插入的转座子。
小Tn5转座子插在359位核苷酸和80位氨基酸上。
这些序列显示出与大肠杆菌K12(EMBL登记号AE000378)的yggN基因的339-1054位核苷酸具有98.5％的序列同一性且在氨基酸水平上具有99.6％的同一性。
尽管yggN基因的序列是已知的，但是其编码的蛋白质的功能尚未确定。
测试新型基因对毒力的减毒作用且证实该新型基因是以0.43的竞争指数被减毒的。
实施例5通过在相同区内插入转座子还发现了几种突变体。对该区的克隆和测序显示了表示为SEQ ID NO.10的核苷酸序列。该序列与大肠杆菌K12(EMBL和Genbank登记号AJ005830、AE000459和AE000167)的tatABCD操纵子具有同源性。该操纵子编码推定质量为9.6kD、18.4kD、28.9kD和29.5kD的蛋白质，它们起Sec依赖性蛋白质输出途径中成分的作用。在细胞质中结合辅因子后，该途径使全折叠的蛋白质通过门控孔移位至周质。
对核苷酸序列的翻译显示了相当于tatA的蛋白质(SEQ IDNO.11)、相当于tatB的序列(SEQ ID NO.12)、相当于tatC的序列(SEQ ID NO.13)和相当于tatD的序列(SEQ ID NO.14)。
由STM鉴定的突变体中的小Tn5转座子定位于SEQ ID NO.10的1429和2226位核苷酸上。这些转座子的插入破坏了tatB蛋白质序列的50位氨基酸和tatC蛋白质序列的143位氨基酸。
测试tatB和tatC基因对毒力的减毒作用且证实这些基因分别以0.0012和0.0039的竞争指数被减毒。当在全身感染的相同模型中测试单一感染时，这些基因在毒性上也发生了弱化。
实施例6在相当于表示为SEQ ID NO.15的大肠杆菌K12的tatE基因的区内通过插入方式使另一种突变体失活。该序列的翻译如SEQ ID NO.16所示。tatE基因显示出与大肠杆菌K12基因(登记号AE000167)的6719-7306位核苷酸具有98％的同一性。
为了确定tatA、tatD和tatE基因是否需要毒性，在它们各自中构建非极性缺失突变。使用下列引物扩增位于各tatA、tatD和tatE基因侧翼的DNA区tatA5’-TCG TCT AGA GAT GAT GGT GAT GGA GCG-3’(SEQ ID NO.53)5’-GAA CTG CAG CCA AAT ACT GAT ACC ACC C-3’(SEQ ID NO.54)5’-GAA CTG CAG GCT AAA ACA GAA GAC GCG-3’(SEQ ID NO.55)5’-CAT GCA TGC ACT CCA TAT GAC AAC CGC-3’(SEQ ID NO.56)将引物SEQ ID NO.53和SEQ ID NO.54用于扩增tatA上游的DNA序列；将引物SEQ ID NO.55和SEQ ID NO.56用于扩增tatA下游的DNA序列。
tatD
5’-TCG TCT AGA ATG AAG CTG CGC ATG AGG-3’(SEQ ID NO.57)5’-CAA CTG CAG TCG CAA ATT GCG AAC TGG-3’(SEQ ID NO.58)5’-CAA CTG CAG ACC GCA ACT TTT CGA CCC-3’(SEQ ID NO.59)5’-CAT GCA TGC CAG TGA GCC ATT GTT CCC-3’(SEQ ID NO.60)将引物SEQ ID NO.57和SEQ ID NO.58用于扩增tatD上游的DNA序列；将引物SEQ ID NO.59和SEQ ID NO.60用于扩增tatD下游的DNA序列。
tatE5’-TGC TCT AGA TAC GAC TCT GAC AGG AGG-3’(SEQ ID NO.61)5’-TCA GAT ATC AAC TAC CAG CAG TTT GG-3’(SEQ ID NO.62)5’-TCA GAT ATC CAT AAA GAG TGA CGT GGC-3’(SEQ ID NO.63)5’-TGC TCT AGA AAA CGT GGC AAC AGA GCG-3’(SEQ ID NO.64)将引物SEQ ID NO.61和SEQ ID NO.62用于扩增tatE上游的DNA序列；将引物SEQ ID NO.63和SEQ ID NO.64用于扩增tatE下游的DNA序列。
在将这些侧翼DNA片段克隆入pUC19中后，将非极性aphT卡那霉素抗性弹夹(Galan等《细菌学杂志》(J.Bacteriol)1992；1744338-4349)插入侧翼DNA片段之间以便取代tatA、tatD和tatE基因。然后将这些DNA片段转入自杀载体pCVD442(Blomfield等《分子微生物学》(Mol.Micro.)1991；51447-1457)。接着通过将pCVD442构建体连入野生型大肠杆菌K1后的等位转移使大肠杆菌K1tatA、tatD和tatE基因的染色体拷贝发生突变。
对受到破坏的tatA、tatD和tatE基因测试对毒力的减毒作用(Achtman等，文献同上)。
没有一种基因在分离过程中缺失时被减毒。这些基因仍然可在毒性中起作用，且为了测试这种情况，通过在tatA和tatE基因中发生缺失来制备突变体。对双重突变体测试经与野生型菌株的混合型感染的毒力的减毒作用且证明该双重突变体以0.0017的竞争指数被减毒。因此看来可以混合使用tatA、tatD和tatE基因以便产生无毒性微生物。
由于大肠杆菌K1 tatABCD基因与存在于鼠伤寒沙门氏菌基因组和脑膜炎奈瑟氏球菌基因组中的推定tatABCD基因具有相似性，所以看起来可能的是在这些和其它生物体中tat系统也可能需要毒性。通过用下列引物扩增位于tatC基因侧翼的DNA来构建鼠伤寒沙门氏菌tatC基因(SEQ ID NO.17)中的缺失5’-TGC TCT AGA AGG CGT TGT CGA TCC TG-3’(SEQ ID NO.65)5’-GAA CTG CAG GAA AAG GCC GAG CAG ACT G-3’(SEQ ID NO.66)5’-GAA CTG CAG TAC AGC CAT GTT TAC GGT-3’(SEQ ID NO.67)5’-CAT GCA TGC GGT GTA CGA CAG TTT GCG-3’(SEQ ID NO.68)将引物SEQ ID NO.65和SEQ ID NO.66用于扩增鼠伤寒沙门氏菌tatC基因下游的DNA序列；将引物SEQ ID NO.67和SEQ ID NO.68用于扩增鼠伤寒沙门氏菌tatC基因上游的DNA序列。
将所编码的tatC基因的两个区的氨基酸序列表示为SEQ ID NO.18和SEQ ID NO.19。
在将这些侧翼DNA片段克隆入pUC19中后，将非极性卡那霉素抗性弹夹(aphT)插入侧翼DNA片段之间以便取代鼠伤寒沙门氏菌tatC基因。然后将该DNA片段转入自杀载体pCVD442。接着通过将pCVD442构建体连入野生型鼠伤寒沙门氏菌菌株TML和SL1344后的等位转移使鼠伤寒沙门氏菌tatC基因的染色体拷贝发生突变。
在使用混合型和单一型感染的全身感染的小鼠模型体内对破坏的鼠伤寒沙门氏菌tatC基因测试毒力的减毒作用。对于混合型感染来说，给6-7周龄balbC小鼠经腹膜内接种104个细菌细胞。在比较3天后存在于脾中的突变体和野生型细菌的数量后来计算竞争指数。对于单一型感染来说，经腹膜内或口服给小鼠接种不同剂量并对小鼠的存活率监测17天。菌株的毒性得到弱化，SL1344 tatC和TML tatC缺失菌株的竞争指数分别为0.078和0.098。
在单一型感染中，小鼠的存活比野生型对照组小鼠的存活延长。
还通过来自脑膜炎奈瑟氏球菌的tat序列证明了序列同源性。将来自脑膜炎奈瑟氏球菌的基因序列表示为SEQ ID NO.20并将所编码的tatC的氨基酸序列表示为SEQ ID NO.21。
为了测试毒性，使用下列引物生成缺失突变体5’-TGCTCTAGACACATCATGGGCACACC-3’(SEQ ID NO.69)5’-GAACTGCAGAACCGTCCACATCAGGCG-3’(SEQ ID NO.70)5’-GAACTGCAGACCCTGCTTGCCATTCCG-3’(SEQ ID NO.71)5’-GAACTGCAGACCCTGCTTGCCATTCCG-3’(SEQ ID NO.72)在将DNA片段和aphT卡那霉素抗性弹夹克隆入pUC19后进行上述对鼠伤寒沙门氏菌所概括的步骤。通过将以pUC19为基础的构建体转化入野生型脑膜炎奈瑟氏球菌细胞而使脑膜炎奈瑟氏球菌tatC基因的染色体拷贝发生突变。
对所得转化体的DNA分析表明所有转化体均是部分二倍体且含有野生型和突变型tatC基因拷贝。这表明对tatC基因已经缺失的突变体的分离存在一定的选择作用。
对极性和非极性构建体的进一步研究证实转化体不在选择性培养基上生长。这提示脑膜炎奈瑟氏球菌tatC基因是该生物体体外生长所必需的。
实施例7在本文鉴定为SEQ ID NO.22的核苷酸序列内的3981位核苷酸上根据插入的转座子来鉴定另外一种突变体。本文定义为eck1的序列显示出与来自许多细菌的几种1组糖基转移酶的序列同源性。还证实了与大肠杆菌K12的gnd基因(SEQ ID NO.22的4197-4604位核苷酸上)的序列同源性。
将翻译的大肠杆菌eck1基因表示为SEQ ID NO.26。已经如上所述测试了该基因的毒力减毒作用且证实该基因以0.025的竞争指数被减毒。
还根据DNA序列(SEQ ID NO.22)鉴定了几种可读框(ORF)。将它们中的第一种在本文中定义为MS1并将翻译产物表示为SEQ IDNO.25。证实其氨基酸序列与来自大肠杆菌血清型O111(TrEMBL数据库登记号AAD46732)的推定糖基转移酶具有50.3％的同一性。该氨基酸序列还显示出与来自大肠杆菌K1的eck1蛋白质的同源性以及与来自小肠结膜炎耶尔森氏菌(TrEMBL数据库登记号Q56917)的TrsE蛋白质的同源性。
本文中鉴定为MS2的第二种可读框具有表示为SEQ ID NO.24的基因序列。这证明了与来自小肠结膜炎耶尔森氏菌(TrEMBL数据库登记号Q56915)的推定糖基转移酶TrsC的序列同源性以及与来自大肠杆菌血清型O113(TrEMBL数据库登记号AAD50485)的糖基转移酶WbnA的序列同源性。
第三种可读框编码本文鉴定为MS3(SEQ ID NO.23)的产物。其氨基酸序列表现出与来自变异链球菌的鼠李糖基转移酶30.2％的同一性。
如果多个毒力基因成群定位于微生物的基因组上，那么表示为SEQID NO.22的基因序列可以是致病性岛的至少一部分。
实施例8鉴定另外一种在iroCDE操纵子内带有插入的转座子的突变体。将位于小Tn5插入物侧翼的核苷酸序列表示为SEQ ID NO.27和SEQ IDNO.30。
将小Tn5转座子插在SEQ ID NO.27的1272位核苷酸上和SEQ IDNO.30的1位核苷酸上并打断iroD基因。将iroD的N-末端区表示为SEQ ID NO.29并将C-末端区表示为SEQ ID NO.31。
除iroD外，表示为SEQ ID NO.27的基因还编码带有表示为SEQ IDNO.28的氨基酸序列的部分肽。这种氨基酸序列表现出与来自伤寒沙门氏菌的推定ATP结合弹夹转运蛋白iroC 70.9％的同一性。
表示为SEQ ID NO.30的基因序列包括编码带有表示为SEQ IDNO.32的氨基酸序列的肽的可读框且它与来自伤寒沙门氏菌的iroE蛋白质具有序列同源性。
如上所述在毒力的减毒作用的模型中对基因测试表明以0.107的竞争指数对iroD基因进行了减毒。已经通过P1转导将iroD基因中的小Tn5突变重新引入野生型大肠杆菌K1菌株。还以0.1的竞争指数对所得转导体的毒力进行了减毒。这表明减毒表型与iroD内的插入物连接。然而，因对大肠杆菌K1 iroE基因的极性作用而导致减毒是可能的。
实施例9用表示为SEQ ID NO.33的核苷酸序列内插入的转座子鉴定另外一种突变体。将该转座子插在SEQ ID NO.33的2264位核苷酸上。该核苷酸序列表现出与大肠杆菌K12(EMBL登记号AE000456)的aslA/hemY区的序列同源性。aslA编码芳基硫酸酯酶同源物，而hemY与血红素IX的生物合成有关。这证明受到破坏的区至少部分与大肠杆菌K12的aslA/hemY区相同。
将转座子插在SEQ ID NO.33的2264位核苷酸上。该插入位点是来自hemY基因的终止密码子下游的216个核苷酸和来自aslA基因的起始密码子上游的472个核苷酸。
如上所述对新区测试毒力的减毒作用且证实该新区以0.033的竞争指数被减毒。已经通过P1转导将该区中的小Tn5突变重新引入野生型大肠杆菌K1菌株。还以0.1的竞争指数对所得的转导体的毒力进行了减毒。这表明减毒表型与该区中的转座子插入物连接。不过，如上所述构建aslA的极性和非极性缺失突变体并测试其对毒力的减毒作用。
无论是极性还是非极性突变体的毒力均没有弱化且这证明原始转座子突变体的减毒作用并不是因对aslA基因的极性作用而导致的。这表明转座子正在破坏在aslA与hemY之间的基因间隔区内编码的某些其它功能。例如，可能存在某些在该区内编码未翻译的RNA分子诸如与oxyS相似的调节RNA(Altuvia等《细胞》(Cell)1997；9043-53)。另一方面，转座子可能破坏例如与DNA复制相关的某些DNA结构。该DNA区还存在于病原体鼠伤寒沙门氏菌中，从而提示它对其它生物体中的致病性来说可能是重要的。可以将该区(SEQ ID NO.33)用作靶物以鉴定抗微生物药。
实施例10鉴定另外一种突变体并克隆位于小Tn5插入物侧翼的DNA区且它具有表示为SEQ ID NO.34的核苷酸序列。由于mtd2基因产物起胞嘧啶特异性甲基转移酶的作用，所以该核苷酸序列与橙色滑柱菌(EMBL登记号P25265)的mtd2基因具有同源性。在大肠杆菌K12中没有发现mtd2基因且它可以代表致病性岛。
小Tn5转座子插入物定位于SEQ ID NO.34的4773和3764位核苷酸上且证实它可打断mtd2基因。
将mtd2基因的氨基酸序列表示为SEQ ID NO.43。
如上所述对大肠杆菌K1 mtd2基因测试对毒力的减毒作用且证实该基因以0.073的竞争指数被减毒。
除mtd2基因外，还使用本文分别鉴定为MS4-MS16、SEQ IDNOS.48-44和42-35的翻译产物鉴定了一系列可读框。如果可读框定位于潜在致病性岛中，那么这些基因中的突变也可以使毒力弱化。此外，由于已知大肠杆菌和其它细菌可以编码核苷酸序列中不同形式的肽类，所以这些蛋白质中的某些的编码区可以重叠。此外，显示出以Val开始的任意氨基酸序列实际上可以以Met开始。
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<221>CDS<222>(1017)..(2549)<400>1ccattactca gaatgggcgg atacacaata aaaattgttc ttcttattac cgcataaccg 60atgccgaggc acaaaaaaat caccgatagt tttaccatcg agaatttttt attcgtttta 120tcagaatttt ctaaattatt tctgatacgt ttgaatatcc agacgcacag cgtcgtcatg 180accactaaca ccagtaaaaa ccacaggtgt gatattaatt cccaggccaa cgtattatat 240ttgtcataca atgacagtcc aggccaactt tccgctttcc ctttgacgta ttgcagcata 300ataaattgcg gcaatgtcag tagggggatg gctgttaaca tcgggatacc tacacgttcg 360acacgtactt tccaccattt tttcaaggga tagcgtaaaa aaagcatgta ggaaaagtac 420ccggatataa cgaaaaatac ctgcatgcgg aacgagtgga tgaagtcatt aaaaagggtc 480agccataatg acggttcggc gctattcaca tgccatgtat ggctcgaata gattaaagaa 540atatgaaaag ggatccctaa caacatcagc caggcgcgga tggagtcgag gaaatattca 600cgttgcgcgg gtactgggtt catatatggt taactaatct cggatttttc gtcttatccc 660tgtcgggtta tgcctttagg cttgttgcca tagcgacacc gacctgaccg cgccaggcgc 720
aggcttcaag gtttttatgc atagcatcat cgctaccact aaccagaatg gaagcgtctg 780taagacggtt gataaataaa tttgctggca aaccctacac gaagtcgatg cttctgtctt 840taggagaagc acggaaagtg aaaacggttg caatcaggtg cttaatccat gagccagtgt 900gctgaacgat accgggattc tgttgtcgga atggcaggtt atccattaaa atagatcgga 960tcgatataag cacacaaagg gggaagtgct tactaattat gaaacataaa ctacaa atg 1019Met1atg aaa atg cgt tgg ttg agt gct gca gta atg tta acc ctg tat aca 1067Met Lys Met Arg Trp Leu Ser Ala Ala Val Met Leu Thr Leu Tyr Thr5 10 15tct tca agc tgg gct ttc agt att gat gat gtc gca aag caa gct caa 1115Ser Ser Ser Trp Ala Phe Ser Ile Asp Asp Val Ala Lys Gln Ala Gln20 25 30tcc tta gcc ggg aaa ggc tat gag gcg ccc aaa agc aac ttg ccc tcc 1163Ser Leu Ala Gly Lys Gly Tyr Glu Ala Pro Lys Ser Asn Leu Pro Ser35 40 45gtt ttc cgc gat atg aaa tac gcg gac tat cag cag atc cag ttt aat 1211Val Phe Arg Asp Met Lys Tyr Ala Asp Tyr Gln Gln Ile Gln Phe Asn50 55 60 65cat gac aaa gcg tac tgg aac aat ctg aag acc cca ttc aaa ctc gag 1259His Asp Lys Ala Tyr Trp Asn Asn Leu Lys Thr Pro Phe Lys Leu Glu70 75 80ttc tac cat cag ggt atg tac ttc gat acc ccg gtc aaa ata aat gaa 1307Phe Tyr His Gln Gly Met Tyr Phe Asp Thr Pro Val Lys Ile Asn Glu85 90 95gtg act gcc acc gca gtc aaa cga atc aaa tac agc ccg gat tat ttc 1355Val Thr Ala Thr Ala Val Lys Arg Ile Lys Tyr Ser Pro Asp Tyr Phe100 105 110act ttc ggc gat gtt cag cat gac aaa gac acg gta aaa gac ctt ggt 1403Thr Phe Gly Asp Val Gln His Asp Lys Asp Thr Val Lys Asp Leu Gly115 120 125ttt gcc ggt ttc aaa gtg ctt tac ccg atc aac agc aaa gat aaa aac 1451Phe Ala Gly Phe Lys Val Leu Tyr Pro Ile Asn Ser Lys Asp Lys Asn130 135 140 145
gat gaa atc gtc agc atg ctc ggg gcc agc tat ttc cgc gtg att ggt1499Asp Glu Ile Val Ser Met Leu Gly Ala Ser Tyr Phe Arg Val Ile Gly150 155 160gca ggt cag gtt tat ggc ctt tct gca cgc ggc ctg gca att gat acc1547Ala Gly Gln Val Tyr Gly Leu Ser Ala Arg Gly Leu Ala Ile Asp Thr165 170 175gcc ttg cca tcg ggt gaa gaa ttt cca cgc ttc aaa gag ttc tgg atc1595Ala Leu Pro Ser Gly Glu Glu Phe Pro Arg Phe Lys Glu Phe Trp Ile180 185 190gag cgt cca aaa ccg act gat aaa cgt tta acc att tat gca ttg ctt1643Glu Arg Pro Lys Pro Thr Asp Lys Arg Leu Thr Ile Tyr Ala Leu Leu195 200 205gac tcg ccg cgc gcg aca ggt gct tac aaa ttc gta gtt atg cca gga1691Asp Ser Pro Arg Ala Thr Gly Ala Tyr Lys Phe Val Val Met Pro Gly210 215 220 225cgt gac acg gtt gtg gat gtg cag tcg aaa atc tat ctg cgc gat aaa1739Arg Asp Thr Val Val Asp Val Gln Ser Lys Ile Tyr Leu Arg Asp Lys230 235 240gtc ggc aaa ctg ggg gtt gca ccg tta acc agt atg ttc ctg ttt ggg1787Val Gly Lys Leu Gly Val Ala Pro Leu Thr Ser Met Phe Leu Phe Gly245 250 255ccg aac caa ccg tcg cct gca aat aac tat cgt ccg gag ttg cac gac1835Pro Asn Gln Pro Ser Pro Ala Asn Asn Tyr Arg Pro Glu Leu His Asp260 265 270tct aac ggt ctg tct atc cat gct ggt aat ggc gaa tgg atc tgg cgt1883Ser Asn Gly Leu Ser Ile His Ala Gly Asn Gly Glu Trp Ile Trp Arg275 280 285ccg ttg aat aac ccg aaa cat tta gcg gtc agc agc ttc tcg atg gaa1931Pro Leu Asn Asn Pro Lys His Leu Ala Val Ser Ser Phe Ser Met Glu290 295 300 305aac ccg caa ggc ttc ggt cta ttg cag cgt ggt cgt gat ttc tcc cgc1979Asn Pro Gln Gly Phe Gly Leu Leu Gln Arg Gly Arg Asp Phe Ser Arg310 315 320ttt gaa gat ctc gat gat cgt tac gat ctt cgt cca agc gca tgg gtg2027Phe Glu Asp Leu Asp Asp Arg Tyr Asp Leu Arg Pro Ser Ala Trp Val325 330 335
act ccg aaa ggg gag tgg ggc aaa ggc agc gtt gag ctg gtg gaa att2075Thr Pro Lys Gly Glu Trp Gly Lys Gly Ser Val Glu Leu Val Glu Ile340 345 350cca acc aac gat gaa acc aac gat aac atc gtc gct tac tgg acg ccg2123Pro Thr Asn Asp Glu Thr Asn Asp Asn Ile Val Ala Tyr Trp Thr Pro355 360 365gat cag ctg ccg gag ccg ggt aaa gag atg aac ttt aaa tac acc atc2171Asp Gln Leu Pro Glu Pro Gly Lys Glu Met Asn Phe Lys Tyr Thr Ile370 375 380 385acc ttc agc cgt gat gaa gac aaa ctg cat gcg cca gat aac gca tgg2219Thr Phe Ser Arg Asp Glu Asp Lys Leu His Ala Pro Asp Asn Ala Trp390 395 400gtg caa caa acg cgt cgt tca acg ggg gat gtg aag cag tcg aac ctg2267Val Gln Gln Thr Arg Arg Ser Thr Gly Asp Val Lys Gln Ser Asn Leu405 410 415att cgc cag cct gac ggt act atc gcc ttt gtg gtc gat ttt acc ggc2315Ile Arg Gln Pro Asp Gly Thr Ile Ala Phe Val Val Asp Phe Thr Gly420 425 430gct gag atg aaa aaa ctg cca gag gat acc ccg gtc aca gcg caa acc2363Ala Glu Met Lys Lys Leu Pro Glu Asp Thr Pro Val Thr Ala Gln Thr435 440 445agc att ggt gat aat ggt gag ata gtt gaa agc acg gtg cgt tat aac2411Ser Ile Gly Asp Asn Gly Glu Ile Val Glu Ser Thr Val Arg Tyr Asn450 455 460 465ccg gtt acc aaa ggc tgg cgt ctg gtg atg cgt gtg aaa gtg aaa gat2459Pro Val Thr Lys Gly Trp Arg Leu Val Met Arg Val Lys Val Lys Asp470 475 480gcc aag aaa acc act gaa atg cgt gct gcg ctg gtg aat gcc gat cag2507Ala Lys Lys Thr Thr Glu Met Arg Ala Ala Leu Val Asn Ala Asp Gln485 490 495acg ttg agt gaa acc tgg agc tac cag tta cct gcc aat gaa2549Thr Leu Ser Glu Thr Trp Ser Tyr Gln Leu Pro Ala Asn Glu500 505 510taagacaact gagtacattg acgcaatgcc catcgccgca agcgagaaag cggcattgcc 2609gaagactgat atccgcgccg ttcatcaggc gctggatgcc gaacaccgca cctgggcgcg 2669
ggaggatgac tccccgcaag gctcggtaaa ggcgcgtctg gaacaagcct ggccagattc 2729acttgctgat ggacagttaa ttaaagacga cgaagggcgc gatcagctaa aggcgatgcc 2789agaagtaaaa cgctcctcga tgtttcccga cccgtggcgt accaacccgg taggccgttt 2849ctgggatcgc ctgcgtggac gcgatgtgac gccgcgctat ctggctcgtt tgaccaaaga 2909agagcaggag agtgagcaaa agtggcgtac cgtcggtacc atccgccgtt acattctgtt 2969gatcctgacg ctcgcgcaaa ctgttgtcgc gacctggtat atgaagacca ttcttcctta 3029tcaggggtgg gcgctgatta atcctatgga tatggttggt caggatgtgt gggtttcctt 3089tatgcagctt ctgccttata tgctgcaaac cggtatcctg atcctctttg cggtactgtt 3149ctgttgggtg tccgccggat tctggaccgg cgttgatggg cttcctgcaa ctgcttattg 3209gtcgcgataa atacagtata tctgcgtcaa cagttggcga tgaaccatta aacccggagc 3269atcgcacggc gttgatcatg cctatctgta acgaagacgt gaaccgtgtt tttgctggct 3329tgcgtgcaac gtgggaatca gtaaaagcca ccgggaatgc caaacatttt gatgtctaca 3389ttcttagtga cagttataac ccggatatct gcgtcgcaga gcaaaaagcc tggatggagc 3449ttatcgctga agtcggtggc gaaggtcaga ttttctatcg ccgccgccgc cgtcgcgtga 3509agcgtaaaag cggtaatatc gatgacttct gccgtcgctg gggcagccag tacagctaca 3569tggtggtgct ggatgctgac tcggtaatga ccggtgattg tttgtgcggc ctggtgcgcc 3629tgatggaagc caacccgaac gccgggatca ttcagtcgtc gccgaaagcg tccggcatgg 3689atacgctgta tgcgcgctgt cagcagttcg cgacccgcgt gtatgggcca ctgtttacag 3749ccggtttgca cttctggcaa cttggcgagt cgcactactg ggggcataac gcgattatcc 3809gcgtgaaacc gtttatcgag cactgtgcac tggctccgct gccgggcgaa ggttcttttg 3869ccggttcaat cctgtcacat gacttcgtgg aagcggcgtt gatgcgccgt gcaggttggg 3929gggtctggat tgcttacgat ctcccgggtt cttatgaaga attaccgcct aacttgcttg 3989atgagctaaa acgtgaccgc cgctggtgcc acggtaacct gatgaacttc cgtctgttcc 4049tggtgaaggg tatgcacccg gttcaccgtg cggtgttcct gacgggcgtg atgtcttatc 4109
tctccgctcc gctgtggttt atgttcctcg cgctctctac tgcattgcag gtagtacatg 4169cgttgaccga accgcaatac ttcctgcaac cacggcagtt gttcccggta tggccgcagt 4229ggcgtcctga gctggcgatt gcactttttg cttcgaccat ggtgctgttg ttcctgccga 4289agctattgag cattttgctt atctggtgca aaggaacgaa agaa 4333<210>2<211>511<212>PRT<213>大肠杆菌<400>2Met Met Lys Met Arg Trp Leu Ser Ala Ala Val Met Leu Thr Leu Tyr1 5 10 15Thr Ser Ser Ser Trp Ala Phe Ser Ile Asp Asp Val Ala Lys Gln Ala20 25 30Gln Ser Leu Ala Gly Lys Gly Tyr Glu Ala Pro Lys Ser Asn Leu Pro35 40 45Ser Val Phe Arg Asp Met Lys Tyr Ala Asp Tyr Gln Gln Ile Gln Phe50 55 60Asn His Asp Lys Ala Tyr Trp Asn Asn Leu Lys Thr Pro Phe Lys Leu65 70 75 80Glu Phe Tyr His Gln Gly Met Tyr Phe Asp Thr Pro Val Lys Ile Asn85 90 95Glu Val Thr Ala Thr Ala Val Lys Arg Ile Lys Tyr Ser Pro Asp Tyr100 105 110Phe Thr Phe Gly Asp Val Gln His Asp Lys Asp Thr Val Lys Asp Leu115 120 125Gly Phe Ala Gly Phe Lys Val Leu Tyr Pro Ile Asn Ser Lys Asp Lys130 135 140Asn Asp Glu Ile Val Ser Met Leu Gly Ala Ser Tyr Phe Arg Val Ile145 150 155 160Gly Ala Gly Gln Val Tyr Gly Leu Ser Ala Arg Gly Leu Ala Ile Asp165 170 175
Thr Ala Leu Pro Ser Gly Glu Glu Phe Pro Arg Phe Lys Glu Phe Trp180 185 190Ile Glu Arg Pro Lys Pro Thr Asp Lys Arg Leu Thr Ile Tyr Ala Leu195 200 205Leu Asp Ser Pro Arg Ala Thr Gly Ala Tyr Lys Phe Val Val Met Pro210 215 220Gly Arg Asp Thr Val Val Asp Val Gln Ser Lys Ile Tyr Leu Arg Asp225 230 235 240Lys Val Gly Lys Leu Gly Val Ala Pro Leu Thr Ser Met Phe Leu Phe245 250 255Gly Pro Asn Gln Pro Ser Pro Ala Asn Asn Tyr Arg Pro Glu Leu His260 265 270Asp Ser Asn Gly Leu Ser Ile His Ala Gly Asn Gly Glu Trp Ile Trp275 280 285Arg Pro Leu Asn Asn Pro Lys His Leu Ala Val Ser Ser Phe Ser Met290 295 300Glu Asn Pro Gln Gly Phe Gly Leu Leu Gln Arg Gly Arg Asp Phe Ser305 310 315 320Arg Phe Glu Asp Leu Asp Asp Arg Tyr Asp Leu Arg Pro Ser Ala Trp325 330 335Val Thr Pro Lys Gly Glu Trp Gly Lys Gly Ser Val Glu Leu Val Glu340 345 350Ile Pro Thr Asn Asp Glu Thr Asn Asp Asn Ile Val Ala Tyr Trp Thr355 360 365Pro Asp Gln Leu Pro Glu Pro Gly Lys Glu Met Asn Phe Lys Tyr Thr370 375 380Ile Thr Phe Ser Arg Asp Glu Asp Lys Leu His Ala Pro Asp Asn Ala385 390 395 400Trp Val Gln Gln Thr Arg Arg Ser Thr Gly Asp Val Lys Gln Ser Asn405 410 415Leu Ile Arg Gln Pro Asp Gly Thr Ile Ala Phe Val Val Asp Phe Thr420 425 430
Gly Ala Glu Met Lys Lys Leu Pro Glu Asp Thr Pro Val Thr Ala Gln435 440 445Thr Ser Ile Gly Asp Asn Gly Glu Ile Val Glu Ser Thr Val Arg Tyr450 455 460Asn Pro Val Thr Lys Gly Trp Arg Leu Val Met Arg Val Lys Val Lys465 470 475 480Asp Ala Lys Lys Thr Thr Glu Met Arg Ala Ala Leu Val Asn Ala Asp485 490 495Gln Thr Leu Ser Glu Thr Trp Ser Tyr Gln Leu Pro Ala Asn Glu500 505 510<210>3<211>574<212>DNA<213>大肠杆菌<400>3ttcgttgatc ctgtcaccgt ttgttcggtt atttccagcc gtgccaccgt tggtctgcga 60accaaacgct ggaaactgtt ccctgatccc ggaagagtat tcaccgccgc aggtgctggt 120tgataccgat cggttccttg agatgaatcg tcaatgctcc cttgatgatg gttttatgca 180cgcggtgttt aacccgtcat ttaacgctct ggcaaccgca atggcgaccg cgcgtcaccg 240cgccagcaag gtgctggaaa tcgcccgtga ccgccacgtt gaacaggcgc tgaacgagac 300gccagagaag ctgaatcgcg atcgtcgcct ggtgctgcta agcgatccgg tgacgatggc 360ccgtctgcat ttccgcgtct ggaattcccc ggagagatat tcttcatggg tgagttatta 420cgaagggata aagctcaatc cactggcatt gcgtaaaccg gatgcggctt cgcaataaaa 480acgtagttgc ctgatgcgct acgcttatca ggcctacatc gttcctgcaa tttattgatt 540ttgcaagatt ttgtaggtcg gataaggcgt tcac 574<210>4<211>1478<212>DNA<213>大肠杆菌<220>
<221>CDS<222>(25)..(1449)<400>4gggataatgc ctgaggggcc tgta atg cgt atc ggc atg cgg ttg ttg ctg51Met Arg Ile Gly Met Arg Leu Leu Leu
1 5ggc tat ttt tta ctg gtg gcg gtg gcg gcc tgg ttc gta ctg gct att99Gly Tyr Phe Leu Leu Val Ala Val Ala Ala Trp Phe Val Leu Ala Ile10 15 20 25ttt gtc aaa gaa gtt aaa ccg ggc gtg cga aga gca acc gag ggg acg147Phe Val Lys Glu Val Lys Pro Gly Val Arg Arg Ala Thr Glu Gly Thr30 35 40tta atc gac acc gca acg ttg ctg gcg gag ctg gcg cgt ccc gat ttg195Leu Ile Asp Thr Ala Thr Leu Leu Ala Glu Leu Ala Arg Pro Asp Leu45 50 55crc tct ggg gac cca acg cat ggg caa ctg gcg cag gcg ttt aat cag243Leu Ser Gly Asp Pro Thr His Gly Gln Leu Ala Gln Ala Phe Asn Gln60 65 70cta caa cat cgc ccg ttt cgc gcc aat atc ggt ggc att aac aaa gtg291Leu Gln His Arg Pro Phe Arg Ala Asn Ile Gly Gly Ile Asn Lys Val75 80 85cgc aac gaa tat cat gtc tat atg acc gat gcg cag ggc aaa gta ttg339Arg Asn Glu Tyr His Val Tyr Met Thr Asp Ala Gln Gly Lys Val Leu90 95 100 105ttc gat tcg gca aat aaa gcc gtt gga cag gat tat tcg cgc tgg aat387Phe Asp Ser Ala Asn Lys Ala Val Gly Gln Asp Tyr Ser Arg Trp Asn110 115 120gac gtc tgg cta acg ttg cgt ggt cag tat ggt gcg cgc agc acg ttg435Asp Val Trp Leu Thr Leu Arg Gly Gln Tyr Gly Ala Arg Ser Thr Leu125 130 135caa aat cct gcc gat ccc gaa agt tct gtg atg tat gtt gcc gcg ccg483Gln Asn Pro Ala Asp Pro Glu Ser Ser Val Met Tyr Val Ala Ala Pro140 145 150att atg gac ggc tcg cgg ctt att ggc gtt ttg agc gta ggc aaa ccg531Ile Met Asp Gly Ser Arg Leu Ile Gly Val Leu Ser Val Gly Lys Pro155 160 165aac gcg gcg atg gct ccg gtc att aag cgt agc gag cgg cga att tta579Asn Ala Ala Met Ala Pro Val Ile Lys Arg Ser Glu Arg Arg Ile Leu170 175 180 185tgg gcc agc gcc att ttg ttg ggg att gca ctg gtg att ggc gca ggc627Trp Ala Ser Ala Ile Leu Leu Gly Ile Ala Leu Val Ile Gly Ala Gly
190 195 200atg gtt tgg tgg atc aac cgc tct att gcc agg ctc act cgc tat gct675Met Val Trp Trp Ile Asn Arg Ser Ile Ala Arg Leu Thr Arg Tyr Ala205 210 215gat tcc gtc act gac aat aag ccc gtt cct ctc ccc gat ctc ggt agt723Asp Ser Val Thr Asp Asn Lys Pro Val Pro Leu Pro Asp Leu Gly Ser220 225 230agc gag ttg cgt aaa ctc gcg cag gcg ctg gaa agt atg cgc gtg aag771Ser Glu Leu Arg Lys Leu Ala Gln Ala Leu Glu Ser Met Arg Val Lys235 240 245ctg gaa ggg aaa aac tat att gag cag tat gtt tat gcg tta act cat819Leu Glu Gly Lys Asn Tyr Ile Glu Gln Tyr Val Tyr Ala Leu Thr His250 255 260 265gag cta aaa agc cca ctg gcg gcg att cgt ggc gcg gcg gaa att tta867Glu Leu Lys Ser Pro Leu Ala Ala Ile Arg Gly Ala Ala Glu Ile Leu270 275 280cgc gaa ggt ccg ccg ccg gaa gtg gtg gct cgt ttt acc gac aac att915Arg Glu Gly Pro Pro Pro Glu Val Val Ala Arg Phe Thr Asp Asn Ile285 290 295ctg acg caa aat gcg cga atg cag gca ctg gtg gaa acg tta cta cgc963Leu Thr Gln Asn Ala Arg Met Gln Ala Leu Val Glu Thr Leu Leu Arg300 305 310cag gca aga ctg gag aat cgt cag gaa gtc gtt ctg act gct gtt gat1011Gln Ala Arg Leu Glu Asn Arg Gln Glu Val Val Leu Thr Ala Val Asp315 320 325gtg gcg gca tta ttt cgc cgc gtc agc gaa gcg cgc acc gtg cag ttg1059Val Ala Ala Leu Phe Arg Arg Val Ser Glu Ala Arg Thr Val Gln Leu330 335 340 345gca gaa aaa aac atc act ttg cat gtt atg cct act gag gtt aac gtt1107Ala Glu Lys Asn Ile Thr Leu His Val Met Pro Thr Glu Val Asn Val350 355 360gct tct gaa ccg gcg tta ctg gag cag gcg ctg ggg aat tta ctg gat1155Ala Ser Glu Pro Ala Leu Leu Glu Gln Ala Leu Gly Asn Leu Leu Asp365 370 375aac gcc atc gat ttt act ccc gag agc ggt tgc ata acg cta agc gcc1203Asn Ala Ile Asp Phe Thr Pro Glu Ser Gly Cys Ile Thr Leu Ser Ala
380 385 390gaa gtg gat cag gaa tac gtc acc ctt aag gtg ctg gat acc ggt agt1251Glu Val Asp Gln Glu Tyr Val Thr Leu Lys Val Leu Asp Thr Gly Ser395 400 405ggg att cct gac tac gcg ctg tca cgt att ttt gaa cgc ttt tac tct1299Gly Ile Pro Asp Tyr Ala Leu Ser Arg Ile Phe Glu Arg Phe Tyr Ser410 415 420 425ttg ccg cgt gca aat ggg caa aaa agc agc ggt ctg ggg ttg gcg ttt1347Leu Pro Arg Ala Asn Gly Gln Lys Ser Ser Gly Leu Gly Leu Ala Phe430 435 440gtc agt gag gtc gcc cgt ttg ttt aac ggc gaa gtc acg ctg cgc aac1395Val Ser Glu Val Ala Arg Leu Phe Asn Gly Glu Val Thr Leu Arg Asn445 450 455gtg cag gaa ggt ggc gtg ctg gcc tcg ctt cga ctt cac cgt cac ttc1443Val Gln Glu Gly Gly Val Leu Ala Ser Leu Arg Leu His Arg His Phe460 465 470aca tag cttcaaattc ttcccacata gtcttcgta1478Thr475<210>5<211>474<212>PRT<213>大肠杆菌<400>5Met Arg Ile Gly Met Arg Leu Leu Leu Gly Tyr Phe Leu Leu Val Ala1 5 10 15Val Ala Ala Trp Phe Val Leu Ala Ile Phe Val Lys Glu Val Lys Pro20 25 30Gly Val Arg Arg Ala Thr Glu Gly Thr Leu Ile Asp Thr Ala Thr Leu35 40 45Leu Ala Glu Leu Ala Arg Pro Asp Leu Leu Ser Gly Asp Pro Thr His50 55 60Gly Gln Leu Ala Gln Ala Phe Asn Gln Leu Gln His Arg Pro Phe Arg65 70 75 80
Ala Asn Ile Gly Gly Ile Asn Lys Val Arg Asn Glu Tyr His Val Tyr85 90 95Met Thr Asp Ala Gln Gly Lys Val Leu Phe Asp Ser Ala Asn Lys Ala100 105 110Val Gly Gln Asp Tyr Ser Arg Trp Asn Asp Val Trp Leu Thr Leu Arg115 120 125Gly Gln Tyr Gly Ala Arg Ser Thr Leu Gln Asn Pro Ala Asp Pro Glu130 135 140Ser Ser Val Met Tyr Val Ala Ala Pro Ile Met Asp Gly Ser Arg Leu145 150 155 160Ile Gly Val Leu Ser Val Gly Lys Pro Asn Ala Ala Met Ala Pro Val165 170 175Ile Lys Arg Ser Glu Arg Arg Ile Leu Trp Ala Ser Ala Ile Leu Leu180 185 190Gly Ile Ala Leu Val Ile Gly Ala Gly Met Val Trp Trp Ile Asn Arg195 200 205Ser Ile Ala Arg Leu Thr Arg Tyr Ala Asp Ser Val Thr Asp Asn Lys210 215 220Pro Val Pro Leu Pro Asp Leu Gly Ser Ser Glu Leu Arg Lys Leu Ala225 230 235 240Gln Ala Leu Glu Ser Met Arg Val Lys Leu Glu Gly Lys Asn Tyr Ile245 250 255Glu Gln Tyr Val Tyr Ala Leu Thr His Glu Leu Lys Ser Pro Leu Ala260 265 270Ala Ile Arg Gly Ala Ala Glu Ile Leu Arg Glu Gly Pro Pro Pro Glu275 280 285Val Val Ala Arg Phe Thr Asp Asn Ile Leu Thr Gln Asn Ala Arg Met290 295 300Gln Ala Leu Val Glu Thr Leu Leu Arg Gln Ala Arg Leu Glu Asn Arg305 310 315 320Gln Glu Val Val Leu Thr Ala Val Asp Val Ala Ala Leu Phe Arg Arg325 330 335
Val Ser Glu Ala Arg Thr Val Gln Leu Ala Glu Lys Asn Ile Thr Leu340 345 350His Val Met Pro Thr Glu Val Asn Val Ala Ser Glu Pro Ala Leu Leu355 360 365Glu Gln Ala Leu Gly Asn Leu Leu Asp Asn Ala Ile Asp Phe Thr Pro370 375 380Glu Ser Gly Cys Ile Thr Leu Ser Ala Glu Val Asp Gln Glu Tyr Val385 390 395 400Thr Leu Lys Val Leu Asp Thr Gly Ser Gly Ile Pro Asp Tyr Ala Leu405 410 415Ser Arg Ile Phe Glu Arg Phe Tyr Ser Leu Pro Arg Ala Asn Gly Gln420 425 430Lys Ser Ser Gly Leu Gly Leu Ala Phe Val Ser Glu Val Ala Arg Leu435 440 445Phe Asn Gly Glu Val Thr Leu Arg Asn Val Gln Glu Gly Gly Val Leu450 455 460Ala Ser Leu Arg Leu His Arg His Phe Thr465 470<210>6<211>128<212>DNA<213>大肠杆菌<221>CDS<222>(1)..(126)<400>6atg aaa ggt cgc ctg tta gat gct gtc ccg ctc agt tcc cta acg ggc48Met Lys Gly Arg Leu Leu Asp Ala Val Pro Leu Ser Ser Leu Thr Gly1 5 10 15gtt ggc gca gcg ctt agt aac aag ctg gcg aaa atc aac ctg cat acc96Val Gly Ala Ala Leu Ser Asn Lys Leu Ala Lys Ile Asn Leu His Thr20 25 30gta cag gat tta ctc tta cac ctt cct ctg cg 128
Val Gln Asp Leu Leu Leu His Leu Pro Leu35 40<210>7<211>42<212>PRT<213>大肠杆菌<400>7Met Lys Gly Arg Leu Leu Asp Ala Val Pro Leu Ser Ser Leu Thr Gly1 5 10 15Val Gly Ala Ala Leu Ser Asn Lys Leu Ala Lys Ile Asn Leu His Thr20 25 30Val Gln Asp Leu Leu Leu His Leu Pro Leu35 40<210>8<211>1174<212>DNA<213>大肠杆菌<220>
<221>CDS<222>(121)..(837)<400>8agatgcacga tcgagtaggc cggataaggc gtttacgccg catccagcat ggaaaacgcg 60cactttgtta tcaatctggg gccagcaaat gctggcctga tttgttcttg agggaagact 120atg atg cgc aaa atg ctg ctg gcg gca gca ctt tca gtg acg gca atg 168Met Met Arg Lys Met Leu Leu Ala Ala Ala Leu Ser Val Thr Ala Met1 5 10 15acc gct cac gcc gac tac cag tgc agc gtc acg ccg cgt gac gat gtg 216Thr Ala His Ala Asp Tyr Gln Cys Ser Val Thr Pro Arg Asp Asp Val20 25 30att gtc agc ccg caa acc gtg cag gtg aag ggc gaa aac ggc aat ctg 264Ile Val Ser Pro Gln Thr Val Gln Val Lys Gly Glu Asn Gly Asn Leu35 40 45gtg atc acg cca gac ggc aac gtg atg tat aac ggt aag caa tat tcc 312
Val Ile Thr Pro Asp Gly Asn Val Met Tyr Asn Gly Lys Gln Tyr Ser50 55 60ctg aat gcc gcc cag cgc gag cag gcg aag gat tat cag gct gaa cta360Leu Asn Ala Ala Gln Arg Glu Gln Ala Lys Asp Tyr Gln Ala Glu Leu65 70 75 80cgt agc acc ctg ccg tgg att gat gga ggc gcg aaa agc cgc gtc gag408Arg Ser Thr Leu Pro Trp Ile Asp Gly Gly Ala Lys Ser Arg Val Glu85 90 95aaa gct cgt att gcg ctg gat aaa att atc gtt cag gag atg ggc gaa456Lys Ala Arg Ile Ala Leu Asp Lys Ile Ile Val Gln Glu Met Gly Glu100 105 110agc agc aaa atg cgc agc cgt ctg acc aaa ctt gat gcg cag ctg aaa504Ser Ser Lys Met Arg Ser Arg Leu Thr Lys Leu Asp Ala Gln Leu Lys115 120 125gag cag atg aac cgc att atc gaa acg cgc agc gat ggc ctg acg ttt552Glu Gln Met Asn Arg Ile Ile Glu Thr Arg Ser Asp Gly Leu Thr Phe130 135 140cac tat aaa gcc att gat cag gtt cgt gcc gaa ggc cag caa tta gtg600His Tyr Lys Ala Ile Asp Gln Val Arg Ala Glu Gly Gln Gln Leu Val145 150 155 160aat cag gca atg ggc gga att tta cag gac agc att aat gaa atg ggc648Asn Gln Ala Met Gly Gly Ile Leu Gln Asp Ser Ile Asn Glu Met Gly165 170 175gcg aaa gcg gtg ctg aaa agc ggc ggt aac cca tta cag aac gtg ctg696Ala Lys Ala Val Leu Lys Ser Gly Gly Asn Pro Leu Gln Asn Val Leu180 185 190gga agc ctg ggc ggc ctg caa tcc tca atc caa acc gag tgg aaa aag744Gly Ser Leu Gly Gly Leu Gln Ser Ser Ile Gln Thr Glu Trp Lys Lys195 200 205cag gaa aaa gat ttc cag cag ttt ggc aaa gat gtt tgt agc cgc gtt792Gln Glu Lys Asp Phc Gln Gln Phe Gly Lys Asp Val Cys Ser Arg Val210 215 220gtg act ctg gaa gat agc cgc aaa gcc ctg gtc ggg aat tta aaa837Val Thr Leu Glu Asp Ser Arg Lys Ala Leu Val Gly Asn Leu Lys225 230 235taatcctcta ttttaagacg gcataatact tttttatgcc gtttaattct tcgttttgtt 897
acctgcctct aactttgtaa gggcgaattc tgcagatatc catcacactg gcggccgctc 957gagcatgcat ctagagggcc caattcgccc tatagtgagt cgtattacaa ttcactggcc 1017gtcgttttac aaccgtcgtg actgggaaaa ccctggcgtt acccaactta atcgccttgc 1077agcacatccc cctttcgcca gctggcgtaa tagcgaaaag gcccgcaccg atcgcccttc 1137caacagttgc gcacctgatg gccaatggac gcgcctg 1174<210>9<211>239<212>PRT<213>大肠杆菌<400>9Met Met Arg Lys Met Leu Leu Ala Ala Ala Leu Ser Val Thr Ala Met1 5 10 15Thr Ala His Ala Asp Tyr Gln Cys Ser Val Thr Pro Arg Asp Asp Val20 25 30Ile Val Ser Pro Gln Thr Val Gln Val Lys Gly Glu Asn Gly Asn Leu35 40 45Val Ile Thr Pro Asp Gly Asn Val Met Tyr Asn Gly Lys Gln Tyr Ser50 55 60Leu Asn Ala Ala Gln Arg Glu Gln Ala Lys Asp Tyr Gln Ala Glu Leu65 70 75 80Arg Ser Thr Leu Pro Trp Ile Asp Gly Gly Ala Lys Ser Arg Val Glu85 90 95Lys Ala Arg Ile Ala Leu Asp Lys Ile Ile Val Gln Glu Met Gly Glu100 105 110Ser Ser Lys Met Arg Ser Arg Leu Thr Lys Leu Asp Ala Gln Leu Lys115 120 125Glu Gln Met Asn Arg Ile Ile Glu Thr Arg Ser Asp Gly Leu Thr Phe130 135 140His Tyr Lys Ala Ile Asp Gln Val Arg Ala Glu Gly Gln Gln Leu Val145 150 155 160
Asn Gln Ala Met Gly Gly Ile Leu Gln Asp Ser Ile Asn Glu Met Gly165 170 175Ala Lys Ala Val Leu Lys Ser Gly Gly Asn Pro Leu Gln Asn Val Leu180 185 190Gly Ser Leu Gly Gly Leu Gln Ser Ser Ile Gln Thr Glu Trp Lys Lys195 200 205Gln Glu Lys Asp Phe Gln Gln Phe Gly Lys Asp Val Cys Ser Arg Val210 215 220Val Thr Leu Glu Asp Ser Arg Lys Ala Leu Val Gly Asn Leu Lys225 230 235<210>10<211>3406<212>DNA<213>大肠杆菌<220>
<221>CDS<222>(1007)..(1276)<220>
<221>CDS<222>(1280)..(1792)<220>
<221>CDS<222>(1798)..(2574)<220>
<221>CDS<222>(2604)..(3398)<400>10gatgatggtg atggagcgta tttacggcat tccggtgtct gatgttgcga cgctggagaa 60aaacggcacc aacatgaaat tgctggcgga acgcggcgtg caggtgttct tcactcaggt 120ctttcgcgac agctttttcc atgctgatat gcaccctggc aacatcttcg taagctatga 180acacccggaa aacccgaaat atatcggcat tgattgcggg attgttggct cgctaaacaa 240agaagataaa cgctatctgg cggaaaactt tatcgccttc tttaatcgcg actatcgcaa 300
agtggcagag ctacacgtcg attctggttg ggtgccacca gataccaacg ttgaagagtt 360cgaatttgcc attcgtacgg tctgtgaacc tatctttgag aaaccgctgg ccgaaatttc 420gtttggacat gtactgttaa atctgtttaa tacggcgcgt cgcttcaata tggaagtgca 480gccgcaactg gtgttactcc agaaaaccct gctctacgtc gaaggggtag gacgccagct 540ttatccgcaa ctcgatttat ggaaaacggc gaagcctttc ctggagtcgt ggattaaaga 600tcaggtcggt attcctgcgc tggtgagagc atttaaagaa aaagcgccgt tctgggtcga 660aaaaatgcca gaactgcctg aactggttta cgacagtttg cgccagggca agtatttaca 720gcatagtgtt ggtaagattg cccgcgagct tcagtcaaat catgtacgtc agggacaatt 780cgcgttattt tctcggaatt ggcgctacgt tagtatttaa gtggcacatt cttgttggtc 840agccgacctg aatgggggct gatgcccggc tggttaatgg caggtggtct gatcgcctgg 900tttgtccggt tggcgcaaaa cacgctgatt ttttcatcgc tcaaggcggg ccgtgtaacg 960tataatgcgg ctttgtttaa tcatcatcta ccacagagga acatgt atg ggt ggt1015Met Gly Gly1atc agt att tgg cag tta ttg att att gcc gtc atc gtt gta ctg ctt 1063Ile Ser Ile Trp Gln Leu Leu Ile Ile Ala Val Ile Val Val Leu Leu5 10 15ttt ggc acc aaa aag ctc ggc tcc atc ggt tcc gat ctt ggt gcg tcg 1111Phe Gly Thr Lys Lys Leu Gly Ser Ile Gly Ser Asp Leu Gly Ala Ser20 25 30 35atc aaa ggc ttt aaa aaa gca atg agc gat gat gaa cca aag cag gat 1159Ile Lys Gly Phe Lys Lys Ala Met Ser Asp Asp Glu Pro Lys Gln Asp40 45 50aaa acc agc cag gat gct gat ttt act gcg aaa act atc gcc gat aag 1207Lys Thr Ser Gln Asp Ala Asp Phe Thr Ala Lys Thr Ile Ala Asp Lys55 60 65cag gcg gat acg aat cag gaa cag gct aaa ata gaa gac gcg aag cgc 1255Gln Ala Asp Thr Asn Gln Glu Gln Ala Lys Ile Glu Asp Ala Lys Arg70 75 80cac gat aaa gag cag gtg taa tct gtg ttt gat atc ggt ttt agc gaa 1303
His Asp Lys Glu Gln Val Val Phe Asp Ile Gly Phe Ser Glu85 90 95ctg cta ttg gtg ttc atc atc ggc ctc gtc gtt ctg ggg ccg caa cga1351Leu Leu Leu Val Phe Ile Ile Gly Leu Val Val Leu Gly Pro Gln Arg100105 110ctg cct gtg gcg gta aaa acg gta gcg ggc tgg att cgc gcg ttg cgt1399Leu Pro Val Ala Val Lys Thr Val Ala Gly Trp Ile Arg Ala Leu Arg115 120 125 130tca ctg gcg aca acg gtg cag aac gaa ctg acc cag gag tta aaa ctc1447Ser Leu Ala Thr Thr Val Gln Asn Glu Leu Thr Gln Glu Leu Lys Leu135 140 145cag gag ttt cag gac agt ctg aaa aag gtt gaa aag gcg agc ctc act1495Gln Glu Phe Gln Asp Ser Leu Lys Lys Val Glu Lys Ala Ser Leu Thr150 155 160aac ctg acg ccc gaa ctg aaa gcg tcg atg gat gaa tta cgc cag gct1543Asn Leu Thr Pro Glu Leu Lys Ala Ser Met Asp Glu Leu Arg Gln Ala165 170 175gcg gag tcg atg aaa cgt tcc tac gtt gca aac gat cct gaa aag gcg1591Ala Glu Ser Met Lys Arg Ser Tyr Val Ala Asn Asp Pro Glu Lys Ala180 185 190agc gat gaa gcg cac acc atc cat aac ccg gtg gtg aaa gac aat gaa1639Ser Asp Glu Ala His Thr Ile His Asn Pro Val Val Lys Asp Asn Glu195 200 205 210act gcg cat gaa ggc gta acg cct gct gct gca caa acg cag gcc agt1687Thr Ala His Glu Gly Val Thr Pro Ala Ala Ala Gln Thr Gln Ala Ser215 220 225tcg ccg gaa cag aag cca gaa acc acg cca gag ccg gtg gta aaa cct1735Ser Pro Glu Gln Lys Pro Glu Thr Thr Pro Glu Pro Val Val Lys Pro230 235 240gct gcg gac gct gaa ccg aaa acc gct gca cct tcc cct tcg tcg agt1783Ala Ala Asp Ala Glu Pro Lys Thr Ala Ala Pro Ser Pro Ser Ser Ser245 250 255gat aaa ccg taaac atg tct gta gaa gat act caa ccg ctt atc acg cat 1833Asp Lys Pro Met Ser Val Glu Asp Thr Gln Pro Leu Ile Thr His260 265 270ctg att gag ctg cgt aag cgt ctg ctg aac tgc att atc tcg gtg atc1881
Leu Ile Glu Leu Arg Lys Arg Leu Leu Asn Cys Ile Ile Ser Val Ile275 280 285gtg ata ttc ctg tgt ctg gtc tat ttc gcc aat gac atc tat cac ctg1929Val Ile Phe Leu Cys Leu Val Tyr Phe Ala Asn Asp Ile Tyr His Leu290 295 300 305gta tcc gcg cca ctg atc aag cag ttg ccg caa ggt tca acg atg atc1977Val Ser Ala Pro Leu Ile Lys Gln Leu Pro Gln Gly Ser Thr Met Ile310 315 320gcc acc gac gtg gcc tcg ccg ttc ttt acg ccg atc aag ctg acc ttt2025Ala Thr Asp Val Ala Ser Pro Phe Phe Thr Pro Ile Lys Leu Thr Phe325 330 335atg gtg tcg ctg att ctg tca gcg ccg gtg att ctc tat cag gtg tgg2073Met Val Ser Leu Ile Leu Ser Ala Pro Val Ile Leu Tyr Gln Val Trp340 345 350gcg ttt atc gcc cca gcg ctg tat aag cat gaa cgt cgc ctg gtg gtg2121Ala Phe Ile Ala Pro Ala Leu Tyr Lys His Glu Arg Arg Leu Val Val355 360 365ccg ctg ctg gtt tcc agc tct ctg ctg ttt tat atc ggc atg gcg ttc2169Pro Leu Leu Val Ser Ser Ser Leu Leu Phe Tyr Ile Gly Met Ala Phe370 375 380 385gcc tac ttt gtg gtc ttt ccg ctg gca ttt ggc ttc ctt gcc aat acc2217Ala Tyr Phe Val Val Phe Pro Leu Ala Phe Gly Phe Leu Ala Asn Thr390 395 400gcg ccg gaa ggg gta cag gta tcc acc gac atc gcg agc tat tta agc2265Ala Pro Glu Gly Val Gln Val Ser Thr Asp Ile Ala Ser Tyr Leu Ser405 410 415ttc gtt atg gcg ctg ttt atg gcg ttt ggt gtc tcc ttt gaa gtg ccg2313Phe Val Met Ala Leu Phe Met Ala Phe Gly Val Ser Phe Glu Val Pro420 425 430gtg gca att gtg ctg ctg tgc tgg atg ggg att acc tcg cca gaa gac2361Val Ala Ile Val Leu Leu Cys Trp Met Gly Ile Thr Ser Pro Glu Asp435 440 445tta cgc aaa aaa cgc ccg tat gtg ctg gtt ggt gca ttc gtt gtc ggg2409Leu Arg Lys Lys Arg Pro Tyr Val Leu Val Gly Ala Phe Val Val Gly450 455 460 465atg ttg ctg acg ccg ccg gat gtc ttc tcg caa acg ctg ttg gcg atc2457
Met Leu Leu Thr Pro Pro Asp Val Phe Ser Gln Thr Leu Leu Ala Ile470 475 480cct atg tac tgc ctg ttt gaa atc ggt gtc ttc ttc tca cgc ttt tac 2505Pro Met Tyr Cys Leu Phe Glu Ile Gly Val Phe Phe Ser Arg Phe Tyr485 490 495gtt ggt aaa ggg cga aac cgg gaa gag gaa aac gac gct gaa gca gaa2553Val Gly Lys Gly Arg Asn Arg Glu Glu Glu Asn Asp Ala Glu Ala Glu500 505 510agc gaa aaa act gaa gaa taa attcaaccgc ccgtcagggc ggttgtcat atg2606Ser Glu Lys Thr Glu Glu Met515 520gag tac agg atg ttt gat atc ggc gtt aat ttg acc agt tcg caa ttt2654Glu Tyr Arg Met Phe Asp Ile Gly Val Asn Leu Thr Ser Ser Gln Phe525 530 535gcg aaa gac cgt gat gat gtt gta gcg cgc gct ttt gac gcg gga gtt2702Ala Lys Asp Arg Asp Asp Val Val Ala Arg Ala Phe Asp Ala Gly Val540 545 550aat ggg cta ctc atc acc ggt acc aat ctg cgt gaa agc cag cag gcg2750Asn Gly Leu Leu Ile Thr Gly Thr Asn Leu Arg Glu Ser Gln Gln Ala555 560 565caa aag ctg gcg cgt cag tat tcg tcc tgt tgg tca acg gcg ggc gta2798Gln Lys Leu Ala Arg Gln Tyr Ser Ser Cys Trp Ser Thr Ala Gly Val570 575 580 585cat cct cac gac agc agc cag tgg caa gct gtg act gaa gaa gcg att2846His Pro His Asp Ser Ser Gln Trp Gln Ala Val Thr Glu Glu Ala Ile590 595 600att gag ctg gcc gcg cag cca gaa gtg gtg gcg att ggt gaa tgt ggt2894Ile Glu Leu Ala Ala Gln Pro Glu Val Val Ala Ile Gly Glu Cys Gly605 610 615ctc gac ttt aac cgc aac ttt tcg acg ccg gaa gag cag gaa cgc gct2942Leu Asp Phe Asn Arg Asn Phe Ser Thr Pro Glu Glu Gln Glu Arg Ala620 625 630ttt gtt gcc cag cta cgc att gcc gca gaa tta aac atg ccg gta ttt2990Phe Val Ala Gln Leu Arg Ile Ala Ala Glu Leu Asn Met Pro Val Phe635 640 645atg cac tgt cgc gat gcc cac gag cgg ttt atg aca ttg ctg gag ccg3038
Met His Cys Arg Asp Ala His Glu Arg Phe Met Thr Leu Leu Glu Pro650 655 660 665tgg ctg gat aaa ctg cct ggt gcg gtt ctt cat tgc ttt acc ggc aca3086Trp Leu Asp Lys Leu Pro Gly Ala Val Leu His Cys Phe Thr Gly Thr670 675 680cgc gaa gag atg cag gcg tgc gtg gcg tgt gga att tat atc ggc att3134Arg Glu Glu Met Gln Ala Cys Val Ala Cys Gly Ile Tyr Ile Gly Ile685 690 695acc ggt tgg gtt tgc gat gaa cga cgc ggg ctg gag ctg cgg gaa ttg3182Thr Gly Trp Val Cys Asp Glu Arg Arg Gly Leu Glu Leu Arg Glu Leu700 705 710ttg ccg ttg att ccg gcg gag aaa ttg ctg atc gaa act gat gcg ccg3230Leu Pro Leu Ile Pro Ala Glu Lys Leu Leu Ile Glu Thr Asp Ala Pro715 720 725tat ctg ctc cct cgc gat ctc acg cca aag cca tca tcc cgg cgc aac3278Tyr Leu Leu Pro Arg Asp Leu Thr Pro Lys Pro Ser Ser Arg Arg Asn730 735 740 745gag cca gcc cat ctg ccc cat att ttg caa cgt att gcg cac tgg cgt3326Glu Pro Ala His Leu Pro His Ile Leu Gln Arg Ile Ala His Trp Arg750 755 760gga gaa gat gcc gca tgg ctg gct gcc acc acg gat gcc aat gtc aaa3374Gly Glu Asp Ala Ala Trp Leu Ala Ala Thr Thr Asp Ala Asn Val Lys765 770 775aca ctg ttt ggg att gcg ttt tag agtttgcg 3406Thr Leu Phe Gly Ile Ala Phe780 785<210>11<211>89<212>PRT<213>大肠杆菌<400>11Met Gly Gly Ile Ser Ile Trp Gln Leu Leu Ile Ile Ala Val Ile Val1 5 10 15Val Leu Leu Phe Gly Thr Lys Lys Leu Gly Ser Ile Gly Ser Asp Leu20 25 30
Gly Ala Ser Ile Lys Gly Phe Lys Lys Ala Met Ser Asp Asp Glu Pro35 40 45Lys Gln Asp Lys Thr Ser Gln Asp Ala Asp Phe Thr Ala Lys Thr Ile50 55 60Ala Asp Lys Gln Ala Asp Thr Asn Gln Glu Gln Ala Lys Ile Glu Asp65 70 75 80Ala Lys Arg His Asp Lys Glu Gln Val85<210>12<211>171<212>PRT<213>大肠杆菌<400>12Val Phe Asp Ile Gly Phe Ser Glu Leu Leu Leu Val Phe Ile Ile Gly1 5 10 15Leu Val Val Leu Gly Pro Gln Arg Leu Pro Val Ala Val Lys Thr Val20 25 30Ala Gly Trp Ile Arg Ala Leu Arg Ser Leu Ala Thr Thr Val Gln Asn35 40 45Glu Leu Thr Gln Glu Leu Lys Leu Gln Glu Phe Gln Asp Ser Leu Lys50 55 60Lys Val Glu Lys Ala Ser Leu Thr Asn Leu Thr Pro Glu Leu Lys Ala65 70 75 80Ser Met Asp Glu Leu Arg Gln Ala Ala Glu Ser Met Lys Arg Ser Tyr85 90 95Val Ala Asn Asp Pro Glu Lys Ala Ser Asp Glu Ala His Thr Ile His100 105 110Asn Pro Val Val Lys Asp Asn Glu Thr Ala His Glu Gly Val Thr Pro115 120 125Ala Ala Ala Gln Thr Gln Ala Ser Ser Pro Glu Gln Lys Pro Glu Thr130 135 140Thr Pro Glu Pro Val Val Lys Pro Ala Ala Asp Ala Glu Pro Lys Thr145 150 155 160
Ala Ala Pro Ser Pro Ser Ser Ser Asp Lys Pro165 170<210>13<211>258<212>PRT<213>大肠杆菌<400>13Met Ser Val Glu Asp Thr Gln Pro Leu Ile Thr His Leu Ile Glu Leu1 5 10 15Arg Lys Arg Leu Leu Asn Cys Ile Ile Ser Val Ile Val Ile Phe Leu20 25 30Cys Leu Val Tyr Phe Ala Asn Asp Ile Tyr His Leu Val Ser Ala Pro35 40 45Leu Ile Lys Gln Leu Pro Gln Gly Ser Thr Met Ile Ala Thr Asp Val50 55 60Ala Ser Pro Phe Phe Thr Pro Ile Lys Leu Thr Phe Met Val Ser Leu65 70 75 80Ile Leu Ser Ala Pro Val Ile Leu Tyr Gln Val Trp Ala Phe Ile Ala85 90 95Pro Ala Leu Tyr Lys His Glu Arg Arg Leu Val Val Pro Leu Leu Val100 105 110Ser Ser Ser Leu Leu Phe Tyr Ile Gly Met Ala Phe Ala Tyr Phe Val115 120 125Val Phe Pro Leu Ala Phe Gly Phe Leu Ala Asn Thr Ala Pro Glu Gly130 135 140Val Gln Val Ser Thr Asp Ile Ala Ser Tyr Leu Ser Phe Val Met Ala145 150 155 160Leu ghe Met Ala Phe Gly Val Ser Phe Glu Val Pro Val Ala Ile Val165 170 175Leu Leu Cys Trp Met Gly Ile Thr Ser Pro Glu Asp Leu Arg Lys Lys180 185 190Arg Pro Tyr Val Leu Val Gly Ala Phe Val Val Gly Met Leu Leu Thr
195 200 205Pro Pro Asp Val Phe Ser Gln Thr Leu Leu Ala Ile Pro Met Tyr Cys210 215 220Leu Phe Glu Ile Gly Val Phe Phe Ser Arg Phe Tyr Val Gly Lys Gly225 230 235 240Arg Asn Arg Glu Glu Glu Asn Asp Ala Glu Ala Glu Ser Glu Lys Thr245 250 255Glu Glu<210>14<211>264<212>PRT<213>大肠杆菌<400>14Met Glu Tyr Arg Met Phe Asp Ile Gly Val Asn Leu Thr Ser Ser Gln1 5 10 15Phe Ala Lys Asp Arg Asp Asp Val Val Ala Arg Ala Phe Asp Ala Gly20 25 30Val Asn Gly Leu Leu Ile Thr Gly Thr Asn Leu Arg Glu Ser Gln Gln35 40 45Ala Gln Lys Leu Ala Arg Gln Tyr Ser Ser Cys Trp Ser Thr Ala Gly50 55 60Val His Pro His Asp Ser Ser Gln Trp Gln Ala Val Thr Glu Glu Ala65 70 75 80Ile Ile Glu Leu Ala Ala Gln Pro Glu Val Val Ala Ile Gly Glu Cys85 90 95Gly Leu Asp Phe Asn Arg Asn Phe Ser Thr Pro Glu Glu Gln Glu Arg100 105 110Ala Phe Val Ala Gln Leu Arg Ile Ala Ala Glu Leu Asn Met Pro Val115 120 125Phe Met His Cys Arg Asp Ala His Glu Arg Phe Met Thr Leu Leu Glu130 135 140Pro Trp Leu Asp Lys Leu Pro Gly Ala Val Leu His Cys Phe Thr Gly
145 150 155 160Thr Arg Glu Glu Met Gln Ala Cys Val Ala Cys Gly Ile Tyr Ile Gly165 170 175Ile Thr Gly Trp Val Cys Asp Glu Arg Arg Gly Leu Glu Leu Arg Glu180 185 190Leu Leu Pro Leu Ile Pro Ala Glu Lys Leu Leu Ile Glu Thr Asp Ala195 200 205Pro Tyr Leu Leu Pro Arg Asp Leu Thr Pro Lys Pro Ser Ser Arg Arg210 215 220Asn Glu Pro Ala His Leu Pro His Ile Leu Gln Arg Ile Ala His Trp225 230 235 240Arg Gly Glu Asp Ala Ala Trp Leu Ala Ala Thr Thr Asp Ala Asn Val245 250 255Lys Thr Leu Phe Gly Ile Ala Phe260<210>15<211>586<212>DNA<213>大肠杆菌<220>
<221>CDS<222>(170)..(370)<400>15tcttaaacaa ccgtcgcttt gcgccgccgc aattattatg atgttttttt actcggcgct 60tgattcacct tgttacagat tgctattgtg tgcgcgcgtc gaatgaccgt taatattctc 120tggtttttaa ggcgcgttct gttgccggtt atatgtcaag aaggtatct atg ggt gag 178Met Gly Glu1att agt att acc aaa ctg ctg gta gtt gcg gcg ctg gtc gtt ctg ctg 226Ile Ser Ile Thr Lys Leu Leu Val Val Ala Ala Leu Val Val Leu Leu5 10 15ttt ggg act aag aag tta cgt acg ctg ggc gga gac ctt gga gcg gcc 274
Phe Gly Thr Lys Lys Leu Arg Thr Leu Gly Gly Asp Leu Gly Ala Ala20 25 30 35att aaa ggg ttc aag aag gcg atg aat gat gac gat gct gcg gcg aaa322Ile Lys Gly Phe Lys Lys Ala Met Asn Asp Asp Asp Ala Ala Ala Lys40 45 50aaa ggc gca gac gtt gat ctt cag gct gaa aag ctc tct cat aaa gag370Lys Gly Ala Asp Val Asp Leu Gln Ala Glu Lys Leu Ser His Lys Glu55 60 65tgacgtggcg agcaggacgc tccctcaata tcttgttcga tacaaaaacc cgcttcaaaa 430agcgggtttt ttatcagaca gatgtaagta attattacag gattacttaa cttccatccc 490tttcgcctgc aaatcggcgt ggtaagaaga gcggacaaac ggaccgcatg cagcatgggt 550aaagcccatc gccagcgctt cgctttcatt tcgtcg586<210>16<211>67<212>PRT<213>大肠杆菌<400>16Met Gly Glu Ile Ser Ile Thr Lys Leu Leu Val Val Ala Ala Leu Val1 5 10 15Val Leu Leu Phe Gly Thr Lys Lys Leu Arg Thr Leu Gly Gly Asp Leu20 25 30Gly Ala Ala Ile Lys Gly Phe Lys Lys Ala Met Asn Asp Asp Asp Ala35 40 45Ala Ala Lys Lys Gly Ala Asp Val Asp Leu Gln Ala Glu Lys Leu Ser50 55 60His Lys Glu65<210>17<211>4200<212>DNA<213>鼠伤寒沙门氏菌
<220>
<221>CDS<222>(947)..(1444)<220>
<221>CDS<222>(1450)..(1722)<400>17cgcaagtcaa tgtcgtcccg gtcgtatgta aaagtatgtg aatagggcgg gcgaaagcgg 60ctaacaaaga ggcagcgtga aggataatgt gtataatgcg gccctaataa ttcatcatct 120atcacagagg aacatgtatg ggtggtatca gtatttggca gttgttgatt gttgccgtta 180tcgtcgtact gctgttcggc accaaaaaac tcggttccat cggttccgat cttggcgcgt 240ctatcaaagg ctttaaaaag gccatgagcg atgatgatgc caaacaggat aaaaccagtc 300aggacgctga ttttaccgct aaatctatcg cggataagca aggcgaagcg aaaaaggaag 360acgctaaaag ccaagataaa gagcaggtat aatccgtgtt tgatatcggt tttagcgaac 420tgctgttagt gttcgttatc ggcctcattg tgttggggcc gcaacgattg ccagtagcgg 480taaaaacggt agcgggctgg attcgcgcgt tgcggtccct tgcgacaacg gttcagaatg 540aactgactca ggaactgaaa cttcaggagt tccaggacag tctgaaaaaa gtcgaaaagg 600cgagcctgga aaatctgact cccgaactga aagcatctat ggatgaactg cgtcaggcgg 660cggagtcgat gaaacgcacc tacagcgcta acgatcccga acaagcgagc gatgaagcgc 720ataccatcca taatccggtg gtaaaaggga acgaaacgca gcatgagggc gtcacccctg 780ccgccgctga aacacaggcg agcgcgccgg aacaaaagcc ggagcccgtt aaagctaacg 840tgcctgagtc gacggaaacc gcttccgtag ccacgataga cgccgagaag aaatccgctg 900cgcctgttgt cgaatcttcc ccctcgtcga gtgataaacc gtaaac atg gct gta955Met Ala Val1gaa gat act caa ccg ctt atc acg cat ctg atc gag ttg cgt aag cgc 1003Glu Asp Thr Gln Pro Leu Ile Thr His Leu Ile Glu Leu Arg Lys Arg5 10 15ctg cta aac tgc atc gtc gca gta ctt ctg att ttt ctg gcg tta att 1051
Leu Leu Asn Cys Ile Val Ala Val Leu Leu Ile Phe Leu Ala Leu Ile20 25 30 35tat ttc gcc aat gat att tat cat tta gtc gcc gca ccg ctg att aaa1099Tyr Phe Ala Asn Asp Ile Tyr His Leu Val Ala Ala Pro Leu Ile Lys40 45 50cag atg ccg caa ggg gcg aca atg att gcg acg gat gtg gcg tcg ccg1147Gln Met Pro Gln Gly Ala Thr Met Ile Ala Thr Asp Val Ala Ser Pro55 60 65ttt ttt acg cct atc aaa ctc acc ttc atg gtg tct ttg atc tta tcc1195Phe Phe Thr Pro Ile Lys Leu Thr Phe Met Val Ser Leu Ile Leu Ser70 75 80gcg cct gtc att ttg tac cag gtt tgg gcc ttt atc gcc ccg gcg ctg1243Ala Pro Val Ile Leu Tyr Gln Val Trp Ala Phe Ile Ala Pro Ala Leu85 90 95tat aag cat gag cgt cgt ctg gtc gta cct ctg ctg gta tcc agc tcg1291Tyr Lys His Glu Arg Arg Leu Val Val Pro Leu Leu Val Ser Ser Ser100 105 110 115ctg ctt ttc tat att ggt atg gcc ttc gcc tat ttt gtc gta ttc cct1339Leu Leu Phe Tyr Ile Gly Met Ala Phe Ala Tyr Phe Val Val Phe Pro120 125 130ttg gcc ttt ggt ttc ctg acg cat acg gcg ccg gaa ggg gta cag gtt1387Leu Ala Phe Gly Phe Leu Thr His Thr Ala Pro Glu Gly Val Gln Val135 140 145tcg aca gat atc gcc agc tat ctt agc ttt gtc atg gcg ctt ttt atg1435Ser Thr Asp Ile Ala Ser Tyr Leu Ser Phe Val Met Ala Leu Phe Met150 155 160gcc ttt gcg tagcc ttt gaa gtg ccg gtg gcg att gtg ttg ctg tgc tgg 1485Ala Phe Ala Phe Glu Val Pro Val Ala Ile Val Leu Leu Cys Trp165 170 175atg ggc atc acc acg cca gaa gat ttg cgt aaa aaa cgg cct tat atc1533Met Gly Ile Thr Thr Pro Glu Asp Leu Arg Lys Lys Arg Pro Tyr Ile180 185 190ctg gtc ggg gca ttc att gtg gga atg ctg ctt acg ccg cca gat gtt1581Leu Val Gly Ala Phe Ile Val Gly Met Leu Leu Thr Pro Pro Asp Val195 200 205 210ttc tcg caa acg ttg ctg gcg ata ccg atg tac tgc ctg ttt gaa att1629
Phe Ser Gln Thr Leu Leu Ala Ile Pro Met Tyr Cys Leu Phe Glu Ile215 220 225ggc gtt ttc tgc tca cgc ttt tat gtc ggt aag cga cgg acg cgc gac 1677Gly Val Phe Cys Ser Arg Phe Tyr Val Gly Lys Arg Arg Thr Arg Asp230 235 240gaa gat aac gag gcc gaa acc gaa aag gcc gag cac act gaa gac 1722Glu Asp Asn Glu Ala Glu Thr Glu Lys Ala Glu His Thr Glu Asp245 250 255taaacacaac cgcccgccag ggcggttgtc atatgggggc aagcatgttt gatattggcg 1782ttaatttaac cagtagccag tttgcaaaag atcgtgatga tgtggtcgcc cgtgcgtttg 1842cggcgggagt aaaaggtatg ctactgaccg gaacgaacat ccatgaaagt cagcaggcgt 1902taaaactggc gcggcgctac ccccattgtt ggtcgacggc tggcgtccat ccccatgaca 1962gcagtcagtg gtcacccgcg tctgaagacg ccattattgc gctggcgaac cagccggaag 2022tcgtcgctat cggtgagtgc gggctggatt tcaatcgcaa tttttccacg ccgcaggagc 2082aggagcgtgc ctttcaggcg cagctacaaa ttgccgccga attgcagata ccaatcttta 2142tgcactgccg ggacgcgcat gagcgatttc tggtattgct tgatccctgg ctggatagtc 2202ttcctggtgc aatactgcac tgctttaccg gttcacgcca gcaaatgcag gcctgtgtgg 2262atagagggct ctatatcggt attaccgggt gggtttgcga cgaacgacgc gggcttgagc 2322tacgtgaact cttaccgttt attccagcgg aaaagctact gatagaaacc gacgcgccgt 2382atctgttgcc tcgcgatctt acgccgaaac caacgtcacg acgcaacgag cccgcgtatc 2442tgcctcacat cctggagcgc atagcgctat ggcgtggtga agatccgcaa tggttagcgg 2502cgatgacaga tgccaacgcc agaaccttat ttgaggttgt attctgaacg atcgctaaat 2562cttgcgaaaa ccggtgtttt ttacgctctg cttcacttct ttattgagta aattaagcag 2622taacatcgaa cgcgtttcgc catccggttc ggtaaaaatc gctttcagcc cttcaaatgc 2682gccttccgtg atgatgacgc tatcgccggg atagggggtt tcaggatcga caacgccttc 2742gggcttgtag atagaaagct gatgaataac gctggaaggc acgatcgcag gatgccgcca 2802aagcgcacaa aatggctgac gccgcgcgtg gcgttgattg tagtggtatg tatcacttcc 2862
ggatcaaatt caacgaacag ataattagga aagagcggtt cgctgacgga ggtacgtttt 2922ccgcgtacca ttttttccag ggtgatcatc ggtgtcaggc aacttaccgc ttgtctttcg 2982aggtgttcct gagcacgctg aagttgcccg cgtttgcagt acagtaaata ccaggattgc 3042ataatgactc ttatccgctt gttcggggcg caagcatagc aaaagccatg cgcgaagtta 3102attatacact tcatccttta agccgtatct ggattagcgt tggttgccag agttcacgct 3162aatttaacaa aaatacagca tcccgatgat gaacgccgta taatgatgcg cttaccaaga 3222ggctacaatg gacgccatga aatatcacga tttacgcgac ttcctgacgc tacttgagca 3282gcagggggaa ctaaaacgca tcacgctacc tgtggatcct catctggaaa tcacggaaat 3342cgctgaccgc acgctgcgtg ccggtggacc ggcgttgctg tttgaaaatc ctaaaggtta 3402cgccatgccg gtgctgtgca acctttttgg cacgccaaaa cgcgtggcga tgggcatggg 3462gcaggatgat gtttccgcct tacgggaagt gggtaaatta ttagcgtttc ttaaagaacc 3522tgagccgccg aaagcgtttc gcgatctgtt tgacaagctg ccgcagttta agcaagtgct 3582gaatatgccg acgaaacggt tacgcggcgc gccttgccag cagaaaatcg cgtctggcga 3642tgatgtcgat ttaacgcgtc ttcctgtcat gacctgttgg ccggacgacg ccgcgccgct 3702gattacctgg ggactgacgg taacgcgtgg tccgcacaaa gagcggcaaa acctgggcat 3762ttatcgtcag cagttgatag gtaaaaataa gctgattatg cgctggctgt ctcaccgcgg 3822cggcgcgctg gattttcagg agtggttagc cgcgcgtccg ggtgaacgtt tcccggtctc 3882cgtcgcattg ggcgccgatc cggcacgata cttggcgccg tgactcctgt tcccgatact 3942ctgtcggagt atgcctttgc gggcctgctg cgcggcacga aaactgaagt ggttaatgct 4002ttctacgatc tggagtgctg cagcgcgaga tatcttgaag tacatgagcg gagagatgcg 4062cggagacgta tgcgatcata cggcatatat gagtgatagc tcgtcttacg tcacgcaata 4122acagcgtaga tgcatctata tcactatacg cgcgcatgag ctcgtatagg tgcctcatat 4182ctcgtctatc tcaaagtc 4200
<210>18<211>166<212>PRT<213>鼠伤寒沙门氏菌<400>18Met Ala Val Glu Asp Thr Gln Pro Leu Ile Thr His Leu Ile Glu Leu1 5 10 15Arg Lys Arg Leu Leu Asn Cys Ile Val Ala Val Leu Leu Ile Phe Leu20 25 30Ala Leu Ile Tyr Phe Ala Asn Asp Ile Tyr His Leu Val Ala Ala Pro35 40 45Leu Ile Lys Gln Met Pro Gln Gly Ala Thr Met Ile Ala Thr Asp Val50 55 60Ala Ser Pro Phe Phe Thr Pro Ile Lys Leu Thr Phe Met Val Ser Leu65 70 75 80Ile Leu Ser Ala Pro Val Ile Leu Tyr Gln Val Trp Ala Phe Ile Ala85 90 95Pro Ala Leu Tyr Lys His Glu Arg Arg Leu Val Val Pro Leu Leu Val100 105 110Ser Ser Ser Leu Leu Phe Tyr Ile Gly Met Ala Phe Ala Tyr Phe Val115 120 125Val Phe Pro Leu Ala Phe Gly Phe Leu Thr His Thr Ala Pro Glu Gly130 135 140Val Gln Val Ser Thr Asp Ile Ala Ser Tyr Leu Ser Phe Val Met Ala145 150 155 160Leu Phe Met Ala Phe Ala165<210>19<211>91<212>PRT<213>鼠伤寒沙门氏菌<400>19Phe Glu Val Pro Val Ala Ile Val Leu Leu Cys Trp Met Gly Ile Thr1 5 10 15
Thr Pro Glu Asp Leu Arg Lys Lys Arg Pro Tyr Ile Leu Val Gly Ala20 25 30Phe Ile Val Gly Met Leu Leu Thr Pro Pro Asp Val Phe Ser Gln Thr35 40 45Leu Leu Ala Ile Pro Met Tyr Cys Leu Phe Glu Ile Gly Val Phe Cys50 55 60Ser Arg Phe Tyr Val Gly Lys Arg Arg Thr Arg Asp Glu Asp Asn Glu65 70 75 80Ala Glu Thr Glu Lys Ala Glu His Thr Glu Asp85 90<210>20<211>2601<212>DNA<213>脑膜炎奈瑟氏球菌<220>
<221>CDS<222>(1572)..(2339)<400>20agacaaaatc ctaaaaaaag tgattgaaga ggcgggcgaa gtgttgatgg catccaaaga 60caaaaacccg tcccacctgg tttacgaagt tgccgactta tggtttcaca ccatgattct 120tctgacacac cacgacctga aggcggaaga cgtattggac gaacttgcgc gccgccaagg 180tttgtcgggc ttggccgaaa aagccgctcg cacagaatct tgaatttata ttaaaatccg 240cactttccca cattcaatcc gtctgaccgc tgttcagacg gcatcggagc cgttatggac 300aactgtattt tctgcaaaat cgccgccaaa gacattccgg cgcaaaccgt ctatgaagac 360ggcgaaatgg tttgtttcaa agacatcaac cccgctgctc cggttcatct gctgctgatt 420cccaaagtcc atttcgattc gttggcacac gccgcgcccg aacatcagcc ccttttggga 480aaaatgatgc tgaaagttcc cgaaatcgcc aaagcggcag gactggcaga cggcttcaaa 540accctgatca acaccggaaa aggcggcgga caagaggtct tccacctgca tatacacatc 600
atgggcacac ccgtataaac cgttatttca caatcaaccc ctaatactta cttaaggata 660catcatgggc agtttttctc tgacgcactg gattatcgta ctgattatcg tcgttttgat 720attcggcacc aaaaaactgc gcaacgtcgg caaagacctc ggcggtgcgg ttcatgactt 780caaacagggg ctgaacgaag gtacagacgg caaagaagcc caaaaagacg atgtaatcga 840acacaaaaaa gacgaagaca aagcgtaatt tatgtttgat ttcggtttgg gcgagctggt 900ttttgtcggc attatcgccc tgattgtcct cggccccgaa cgcctgcccg aggccgcccg 960caccgccgga cggctcatcg gcaggctgca acgctttgtc ggcagcgtca aacaggaatt 1020tgacacgcaa atcgaactgg aagaactaag gaaggcaaag caggaatttg aagctgccgc 1080tgctcaggtt cgagacagcc tcaaagaaac cggtacggat atggagggta atctgcacga 1140catttccgac ggtctgaagc cttgggaaaa actgcccgaa cagcgcacgc ctgctgattt 1200cggtgtcgat gaaaacggca atccctttcc cgatgcggca aacaccctat tagacggcat 1260ttccgacgtt atgccgtccg aacgttccta cgcttccgcc gaaacccttg gggacagcgg 1320gcaaaccggc agtacagccg aacccgcgga aaccgaccaa gaccgtgcat ggcgggaata 1380cctgactgct tctgccgccg cacccgtcgt acagaccgtc gaagtcagct atatcgatac 1440cgctgttgaa acccctgttc cgcataccac ttcgctgcgt aaacaggcaa taagccgcaa 1500acgcgatttg cgtcctaaat cccgcgccaa acctaaattg cgcgtccgta aatcataaag 1560agggcaatcc g gtg tcc gaa aca caa aac gaa caa ccc gtc caa ccg ctt 1610Val Ser Glu Thr Gln Asn Glu Gln Pro Val Gln Pro Leu1 5 10gtc gag cat ctc atc gag ctg cgc cgc cgc ctg atg tgg acg gtt gtc 1658Val Glu His Leu Ile Glu Leu Arg Arg Arg Leu Met Trp Thr Val Val15 20 25ggt atc tta gtc tgc ttt ttc ggc cta atg ccg ttt gcc caa caa ctc 1706Gly Ile Leu Val Cys Phe Phe Gly Leu Met Pro Phe Ala Gln Gln Leu30 35 40 45tat act ttt atc gcc gac ccg ctg atg gca aac ctg ccc aaa gac acc 1754Tyr Thr Phe Ile Ala Asp Pro Leu Met Ala Asn Leu Pro Lys Asp Thr50 55 60
agc atg att gcc acc gat gtc atc gca cca ttt ttc gtg ccg gtc aaa1802Ser Met Ile Ala Thr Asp Val Ile Ala Pro Phe Phe Val Pro Val Lys65 70 75gtt acc ctg atg gcg gca ttt tta att tcg ctg ccg cat acg ctc tac1850Val Thr Leu Met Ala Ala Phe Leu Ile Ser Leu Pro His Thr Leu Tyr80 85 90caa atc tgg gca ttc gtc gcc ccc gca ctc tac caa aac gaa aaa cgc1898Gln Ile Trp Ala Phe Val Ala Pro Ala Leu Tyr Gln Asn Glu Lys Arg95 100 105ctg att acg ccg ctc gtc ctc tcc agc gtc agc ctg ttt ttc atc ggc1946Leu Ile Thr Pro Leu Val Leu Ser Ser Val Ser Leu Phe Phe Ile Gly110 115 120 125atg gca ttt gcc tac ttt ttg gtt ttc ccc gtc att ttc aaa ttc ctt1994Met Ala Phe Ala Tyr Phe Leu Val Phe Pro Val Ile Phe Lys Phe Leu130 135 140gcc agc gtt acc cct gtc ggt gtc aat atg gcg aca gac atc gac aaa2042Ala Ser Val Thr Pro Val Gly Val Asn Met Ala Thr Asp Ile Asp Lys145 150 155tac ctc tcc ttc atc ttg ggg atg ttt gtc gca ttc ggt aca acg ttt2090Tyr Leu Ser Phe Ile Leu Gly Met Phe Val Ala Phe Gly Thr Thr Phe160 165 170gaa gtc ccc att gtc gtt atc ctg tta acc aaa att ggt gtg gta aca2138Glu Val Pro Ile Val Val Ile Leu Leu Thr Lys Ile Gly Val Val Thr175 180 185acc gaa cag ctc aaa cgc gcc cgc ccc tat gtg att gtc ggc gcg ttt2186Thr Glu Gln Leu Lys Arg Ala Arg Pro Tyr Val Ile Val Gly Ala Phe190 195 200 205gtc att gcc gcc atc atc acg ccg ccc gat gtg att tca caa acc ctg2234Val Ile Ala Ala Ile Ile Thr Pro Pro Asp Val Ile Ser Gln Thr Leu210 215 220ctt gcc att ccg ctg att ctc tta tac gaa gca ggt att tgg ttc gga2282Leu Ala Ile Pro Leu Ile Leu Leu Tyr Glu Ala Gly Ile Trp Phe Gly225 230 235cgc ttt ttc acg cca cgt tca gaa cag gat ggc gac ata cag ccg cct2330Arg Phe Phe Thr Pro Arg Ser Glu Gln Asp Gly Asp Ile Gln Pro Pro240 245 250
gca aca acc tgacactatg ccgtccgaac ctccgcctca taccgccaca 2379Ala Thr Thr255gattaaggaa tacctttgaa taccctctat ttaggttcaa acagcccgcg ccgaatggaa 2439atcctgacac agttgggcta tcaggtcgtc aagctgcctg ccaacatcga cgaaacggtc 2499agacagaacg aagaccctgc ccgttacgtt caaaggatgg cagaagaaaa aaaccgaacc 2559gccctgaccc tcttttgcga aaccaacggc acaatgcccg at2601<210>21<211>256<212>PRT<213>脑膜炎奈瑟氏球菌<400>21Val Ser Glu Thr Gln Asn Glu Gln Pro Val Gln Pro Leu Val Glu His1 5 10 15Leu Ile Glu Leu Arg Arg Arg Leu Met Trp Thr Val Val Gly Ile Leu20 25 30Val Cys Phe Phe Gly Leu Met Pro Phe Ala Gln Gln Leu Tyr Thr Phe35 40 45Ile Ala Asp Pro Leu Met Ala Asn Leu Pro Lys Asp Thr Ser Met Ile50 55 60Ala Thr Asp Val Ile Ala Pro Phe Phe Val Pro Val Lys Val Thr Leu65 70 75 80Met Ala Ala Phe Leu Ile Ser Leu Pro His Thr Leu Tyr Gln Ile Trp85 90 95Ala Phe Val Ala Pro Ala Leu Tyr Gln Asn Glu Lys Arg Leu Ile Thr100 105 110Pro Leu Val Leu Ser Ser Val Ser Leu Phe Phe Ile Gly Met Ala Phe115 120 125Ala Tyr Phe Leu Val Phe Pro Val Ile Phe Lys Phe Leu Ala Ser Val130 135 140Thr Pro Val Gly Val Asn Met Ala Thr Asp Ile Asp Lys Tyr Leu Ser145 150 155 160
Phe Ile Leu Gly Met Phe Val Ala Phe Gly Thr Thr Phe Glu Val Pro165 170 175Ile Val Val Ile Leu Leu Thr Lys Ile Gly Val Val Thr Thr Glu Gln180 185 190Leu Lys Arg Ala Arg Pro Tyr Val Ile Val Gly Ala Phe Val Ile Ala195 200 205Ala Ile Ile Thr Pro Pro Asp Val Ile Ser Gln Thr Leu Leu Ala Ile210 215 220Pro Leu Ile Leu Leu Tyr Glu Ala Gly Ile Trp Phe Gly Arg Phe Phe225 230 235 240Thr Pro Arg Ser Glu Gln Asp Gly Asp Ile Gln Pro Pro Ala Thr Thr245 250 255<210>22<211>4604<212>DNA<213>大肠杆菌<220>
<221>CDS<222>(2982)..(4082)<220>
<221>CDS<222>(1534)..(2637)<220>
<221>CDS<222>(749)..(1531)<220>
<221>CDS<222>(6)..(746)<400>22ggcta gtt gat gat aat ttg aaa ggt caa ggt gca gga aaa aat ttt tta 50Val Asp Asp Asn Leu Lys Gly Gln Gly Ala Gly Lys Asn Phe Leu1 5 10 15tcg ctg ata aag tac agc gag aca gat tat aca att tat tgt gac caa 98
Ser Leu Ile Lys Tyr Ser Glu Thr Asp Tyr Thr Ile Tyr Cys Asp Gln20 25 30gat gat att tgg tta gaa aac aaa ata ttt gaa tta gta aag tat gca146Asp Asp Ile Trp Leu Glu Asn Lys Ile Phe Glu Leu Val Lys Tyr Ala35 40 45aat gaa att aaa ttg aat gta tca gat gcg cct tcg cra gtt tat gct194Asn Glu Ile Lys Leu Asn Val Ser Asp Ala Pro Ser Leu Val Tyr Ala50 55 60gat ggc tat gct tat atg gat ggt gag ggt aca atc gat ttt tct ggg242Asp Gly Tyr Ala Tyr Met Asp Gly Glu Gly Thr Ile Asp Phe Ser Gly65 70 75ata tct aac aat cat gct gat caa tta aag gat ttt ctt ttt ttt aat290Ile Ser Asn Asn His Ala Asp Gln Leu Lys Asp Phe Leu Phe Phe Asn80 85 90 95ggt gga tac caa gga tgt tct att atg ttc aat cgt gca atg acc aaa338Gly Gly Tyr Gln Gly Cys Ser Ile Met Phe Asn Arg Ala Met Thr Lys100 105 110ttt ctt ctg aat tat cga gga ttt gta tat cta cat gac gat atc aca386Phe Leu Leu Asn Tyr Arg Gly Phe Val Tyr Leu His Asp Asp Ile Thr115 120 125aca tta gct gca tac gct ctt ggt aaa gtt tat ttt ctc ccg aaa tac434Thr Leu Ala Ala Tyr Ala Leu Gly Lys Val Tyr Phe Leu Pro Lys Tyr130 135 140ctt atg tta tat aga cag cac acg aat gcg gta act ggt atc aaa aca482Leu Met Leu Tyr Arg Gln His Thr Asn Ala Val Thr Gly Ile Lys Thr145 150 155ttc cgc aat gga ttg act tct aaa ttt aaa tca cca gta aac tat ctt530Phe Arg Asn Gly Leu Thr Ser Lys Phe Lys Ser Pro Val Asn Tyr Leu160 165 170 175tta tca cga aaa cat tat cag gta aaa aaa tct ttt ttt gaa tgt aac578Leu Ser Arg Lys His Tyr Gln Val Lys Lys Ser Phe Phe Glu Cys Asn180 185 190agc tct atc tta tca gag acg aat aaa aaa gtt ttt ttg gat ttt att626Ser Ser Ile Leu Ser Glu Thr Asn Lys Lys Val Phe Leu Asp Phe Ile195 200 205tca ttt tgt gaa tca aat aat aaa ttt aca gat ttt ttt aag tta tgg674
Ser Phe Cys Glu Ser Asn Asn Lys Phe Thr Asp Phe Phe Lys Leu Trp210 215 220cga ggt ggg ttt aga tta aat aac agt aga act aaa tta tta tta aaa722Arg Gly Gly Phe Arg Leu Asn Asn Ser Arg Thr Lys Leu Leu Leu Lys225 230 235ttc tta ata cgg aga aaa ttt agc ga atg att tca ata ctt aca cct 769Phe Leu Ile Arg Arg Lys Phe SerMet Ile Ser Ile Leu Thr Pro240 245250act ttt aat cgg caa cat act tta tca agg cta ttc aat tct ctt ata817Thr Phe Asn Arg Gln His Thr Leu Ser Arg Leu Phe Asn Ser Leu Ile255 260 265 270tta caa act gat aaa gat ttt gag tgg ata ata att gat gat ggt agt865Leu Gln Thr Asp Lys Asp Phe Glu Trp Ile Ile Ile Asp Asp Gly Ser275 280 285ata gat gca aca gcg gta ctt gta gaa gat ttt aga aaa aaa tgt gat913Ile Asp Ala Thr Ala Val Leu Val Glu Asp Phe Arg Lys Lys Cys Asp290 295 300ttt gac ttg att tat tgc tat cag gaa aat aat ggt aag ccc atg gct961Phe Asp Leu Ile Tyr Cys Tyr Gln Glu Asn Asn Gly Lys Pro Met Ala305 310 315tta aac gct ggt gtt aaa gct tgt aga ggc gat tat atc ttt att gtt1009Leu Asn Ala Gly Val Lys Ala Cys Arg Gly Asp Tyr Ile Phe Ile Val320 325 330gac agt gat gat gca cta act ccc gat gcc ata aaa tta att aaa gaa1057Asp Ser Asp Asp Ala Leu Thr Pro Asp Ala Ile Lys Leu Ile Lys Glu335 340 345 350tca ata cat gat tgc tta tct gag aag gaa agt ttc agc gga gtc ggt1105Ser Ile His Asp Cys Leu Ser Glu Lys Glu Ser Phe Ser Gly Val Gly355 360 365ttt aga aaa gca tat ata aaa ggg ggg att att ggt aat gat tta aat1153Phe Arg Lys Ala Tyr Ile Lys Gly Gly Ile Ile Gly Asn Asp Leu Asn370 375 380aat tct tca gaa cat ata tac tat tta aat gcg act gag att agc aat1201Asn Ser Ser Glu His Ile Tyr Tyr Leu Asn Ala Thr Glu Ile Ser Asn385 390 395tta ata aat ggt gat gtt gca tat tgt ttt aaa aaa gaa agt ttg gta1249
Leu Ile Asn Gly Asp Val Ala Tyr Cys Phe Lys Lys Glu Ser Leu Val400 405 410aaa aat cca ttc ccc cgt ata gaa gat gaa aaa ttt gtt cca gaa tta1297Lys Asn Pro Phe Pro Arg Ile Glu Asp Glu Lys Phe Val Pro Glu Leu415 420 425 430tat att tgg aat aaa ata act gac aag gcg aag att cga ttt aac ata1345Tyr Ile Trp Asn Lys Ile Thr Asp Lys Ala Lys Ile Arg Phe Asn Ile435 440 445agc aaa gtt ata tat ctt tgt gag tat ctt gat gat ggt ctt tct aaa1393Ser Lys Val Ile Tyr Leu Cys Glu Tyr Leu Asp Asp Gly Leu Ser Lys450 455 460aat ttc cat aac cag ctt aaa aaa tac cca aag ggg ttt aag att tat1441Asn Phe His Asn Gln Leu Lys Lys Tyr Pro Lys Gly Phe Lys Ile Tyr465 470 475tac aaa gat caa aga aaa cga gag aaa act tat ata aaa aaa aca aag1489Tyr Lys Asp Gln Arg Lys Arg Glu Lys Thr Tyr Ile Lys Lys Thr Lys480 485 490atg cta att aga tat ttg caa tgt tgt tat tat gag aaa ata aa atg 1536Met Leu Ile Arg Tyr Leu Gln Cys Cys Tyr Tyr Glu Lys IleMet495 500 505aaa ata cta ttt gtc att aca ggt tta ggc ctt gga ggt gct gag aag1584Lys Ile Leu Phe Val Ile Thr Gly Leu Gly Leu Gly Gly Ala Glu Lys510 515 520 525cag gtt tgt ctt tta gct gat aaa tta agt tta agc ggg cac cat gta1632Gln Val Cys Leu Leu Ala Asp Lys Leu Ser Leu Ser Gly His His Val530 535 540aag att att tca ctt gga cat atg tct aat aat aaa gtc ttt cct agc1680Lys Ile Ile Ser Leu Gly His Met Ser Asn Asn Lys Val Phe Pro Ser545 550 555gaa aat aat gtt aat gtc att aat gta aat atg tca aaa aac att tct1728Glu Asn Asn Val Asn Val Ile Asn Val Asn Met Ser Lys Asn Ile Ser560 565 570gga gtt ata aaa ggt tgt gtc aga att aga gat gtt ata gct aat ttc1776Gly Val Ile Lys Gly Cys Val Arg Ile Arg Asp Val Ile Ala Asn Phe575 580 585aaa cca gac att gta cac agt cat atg ttt cat gca aac att atc act1824
Lys Pro Asp Ile Val His Ser His Met Phe His Ala Asn Ile Ile Thr590 595 600 605aga ttg tct gta att gga atc aaa aac aga cct ggt att ata tca act1872Arg Leu Ser Val Ile Gly Ile Lys Asn Arg Pro Gly Ile Ile Ser Thr610 615 620gca cat aat aaa aat gaa ggt ggg tat ttc aga atg ctc aca tat aga1920Ala His Asn Lys Asn Glu Gly Gly Tyr Phe Arg Met Leu Thr Tyr Arg625 630 635ata acc gat tgt tta agt gat tgt tgt aca aat gtt agc aaa gaa gca1968Ile Thr Asp Cys Leu Ser Asp Cys Cys Thr Asn Val Ser Lys Glu Ala640 645 650gtg gat gag ttt tta cgg ata aaa gcc ttt aat ccc gct aaa gca att2016Val Asp Glu Phe Leu Arg Ile Lys Ala Phe Asn Pro Ala Lys Ala Ile655 660 665act atg tat aat ggg ata gat acc aat aaa ttt aaa ttt gat tta ttg2064Thr Met Tyr Asn Gly Ile Asp Thr Asn Lys Phe Lys Phe Asp Leu Leu670 675 680 685gca agg agg gaa att cga gac ggt att aat ata aaa aat gat gat ata2112Ala Arg Arg Glu Ile Arg Asp Gly Ile Asn Ile Lys Asn Asp Asp Ile690 695 700tta tta ctt gct gca ggt cgt tta acg tta gct aaa gat tat cct aat2160Leu Leu Leu Ala Ala Gly Arg Leu Thr Leu Ala Lys Asp Tyr Pro Asn705 710 715tta ttg aat gca atg act ctg ctt cct gaa cac ttt aaa ctt att att2208Leu Leu Asn Ala Met Thr Leu Leu Pro Glu His Phe Lys Leu Ile Ile720 725 730att ggt gat ggt gaa ttg cgt gac gaa att aat atg ctt ata aaa aaa2256Ile Gly Asp Gly Glu Leu Arg Asp Glu Ile Asn Met Leu Ile Lys Lys735 740 745ttg caa tta tct aat agg gtg tcc ttg ttg gga gtt aaa aaa aat att2304Leu Gln Leu Ser Asn Arg Val Ser Leu Leu Gly Val Lys Lys Asn Ile750 755 760 765gct ccc tat ttt tct gca tgt gat att ttt gtt ctc tct tct cgt tgg2352Ala Pro Tyr Phe Ser Ala Cys Asp Ile Phe Val Leu Ser Ser Arg Trp770 775 780gaa gga ttt gga tta gtc gtg gca gaa gct atg tca tgt gag cga att2400
Glu Gly Phe Gly Leu Val Val Ala Glu Ala Met Ser Cys Glu Arg Ile785 790 795gtt gtt ggc acg gat tca ggg gga gta aga gaa gtt att ggt gac gat2448Val Val Gly Thr Asp Ser Gly Gly Val Arg Glu Val Ile Gly Asp Asp800 805 810gat ttt ctt gta ccc ata tct gat tca aca caa ctt gca agc aaa att2496Asp Phe Leu Val Pro Ile Ser Asp Ser Thr Gln Leu Ala Ser Lys Ile815 820 825gaa aaa ttg tct ttg agc cag ata cgt gat cac att ggt ttt cgg aat2544Glu Lys Leu Ser Leu Ser Gln Ile Arg Asp His Ile Gly Phe Arg Asn830 835 840 845cgt gag cgt att tta aaa aat ttc tca ata gat act att att atg cag2592Arg Glu Arg Ile Leu Lys Asn Phe Ser Ile Asp Thr Ile Ile Met Gln850 855 860tgg caa gaa ctc tat gga act ata att tgc tca aaa cat gaa agg2637Trp Gln Glu Leu Tyr Gly Thr Ile Ile Cys Ser Lys His Glu Arg865 870 875tagatttata tttggaacgt gtcttttgtt tgaatttaat tcaatctcaa ttgagatttt 2697tgtatttcaa aaataccatc atagctaacg atgattggta tttattttaa gatgctttct 2757ataaatatat tgacgttttt aatgcgccga aacgattggg ctgggaacag agaagtaaaa 2817ctgttttgag aatgaagagt ttttgagatg tttatggata ttaaaaattg atccagtgaa 2877ttaattattt ataataaatc aagatttaat gttaataaat gataatcttt tctgacactc 2937atattaatta tgagtggtac gtttggtaaa cggtaaacta ttat atg aca gct aga 2993Met Thr Ala Arg880aca act aaa gtt ttg cac tta caa tta ctc cca ctc tta agt ggc gtt3041Thr Thr Lys Val Leu His Leu Gln Leu Leu Pro Leu Leu Ser Gly Val885 890 895caa agg gta aca tta aac gaa att agt gcg tta tat act gat tat gat3089Gln Arg Val Thr Leu Asn Glu Ile Ser Ala Leu Tyr Thr Asp Tyr Asp900 905 910tat aca cta gtt tgc tca aaa aaa ggt cca cta aca aaa gca ttg ctg3137Tyr Thr Leu Val Cys Ser Lys Lys Gly Pro Leu Thr Lys Ala Leu Leu915 920 925
gaa tat gat gtc gat tgt cat tgt atc ccc gaa ctt acg aga gaa att3185Glu Tyr Asp Val Asp Cys His Cys Ile Pro Glu Leu Thr Arg Glu Ile930 935 940acc gta aag aat gat ttt aaa gca ttg ttc aag ctt tat aag ttc ata3233Thr Val Lys Asn Asp Phe Lys Ala Leu Phe Lys Leu Tyr Lys Phe Ile945 950 955 960aaa aaa gaa aaa ttt gac att gtg cat aca cat tctt ca aaa aca ggt3281Lys Lys Glu Lys Phe Asp Ile Val His Thr His Ser Ser Lys Thr Gly965 970 975att ttg ggg cga gtt gct gcc aaa tta gca cgt gtt gga aag gtg atc3329Ile Leu Gly Arg Val Ala Ala Lys Leu Ala Arg Val Gly Lys Val Ile980 985 990cac act gta cat ggt ttt tct ttt cca gcc gca tct agt aaa aaa agt3377His Thr Val His Gly Phe Ser Phe Pro Ala Ala Ser Ser Lys Lys Ser99510001005tat tac ctt tat ttt ttc atg gaa tgg ata gca aag ttc ttt acg gat3425Tyr Tyr Leu Tyr Phe Phe Met Glu Trp Ile Ala Lys Phe Phe Thr Asp101010151020aag tta atc gtc ttg aat gta gat gat gaa tat ata gca ata aac aaa3473Lys Leu Ile Val Leu Asn Val Asp Asp Glu Tyr Ile Ala Ile Asn Lys1025 103010351040tta aaa ttc aag cgg gat aaa gtt ttt tta att cct aat gga gta gac3521Leu Lys Phe Lys Arg Asp Lys Val Phe Leu Ile Pro Asn Gly Val Asp104510501055act gat aag ttt tct cct tta gaa aat aaa att tat agt agc acc ttg3569Thr Asp Lys Phe Ser Pro Leu Glu Asn Lys Ile Tyr Ser Ser Thr Leu106010651070aat cta gta atg gtt ggt aga tta tcc aag caa aaa gat cct gag aca3617Asn Leu Val Met Val Gly Arg Leu Ser Lys Gln Lys Asp Pro Glu Thr107510801085tta ttg ctt gct gtt gaa aaa ctg ctg aat gaa aat gtt aat gtt aag3665Leu Leu Leu Ala Val Glu Lys Leu Leu Asn Glu Asn Val Asn Val Lys109010951100ctg aca ctt gta gga gat ggt gaa cta aaa gaa cag tta gaa agc agg3713Leu Thr Leu Val Gly Asp Gly Glu Leu Lys Glu Gln Leu Glu Ser Arg1105 111011151120
ttc aaa cgg caa gat gga cgt ata att ttt cat gga tgg tca gat aac3761Phe Lys Arg Gln Asp Gly Arg Ile Ile Phe His Gly Trp Ser Asp Asn112511301135att gtt aat att tta aaa gtt aat gat ctt ttt ata tta cct tct crt3809Ile Val Asn Ile Leu Lys Val Asn Asp Leu Phe Ile Leu Pro Ser Leu114011451150tgg gag ggt atg cca tta gca att tta gaa gca ttg agc tgt gga ctt3857Trp Glu Gly Met Pro Leu Ala Ile Leu Glu Ala Leu Ser Cys Gly Leu115511601165cca tgt ata gtc act aat att cca ggt aat aat agc tta ata gaa gat3905Pro Cys Ile Val Thr Asn Ile Pro Gly Asn Asn Ser Leu Ile Glu Asp117011751180ggc tat aat ggt tgt ttg ttt gaa att aga gat tgt cag tta tta tct3953Gly Tyr Asn Gly Cys Leu Phe Glu Ile Arg Asp Cys Gln Leu Leu Ser1185 119011951200caa aaa atc atg tca tat gtt ggt aag cca gaa ctg att gca cag caa4001Gln Lys Ile Met Ser Tyr Val Gly Lys Pro Glu Leu Ile Ala Gln Gln120512101215tct acc aat gca cga tca ttt att ctg aaa aat tat gga tta gtt aaa4049Ser Thr Asn Ala Arg Ser Phe Ile Leu Lys Asn Tyr Gly Leu Val Lys122012251230aga aat aat aag gtc aga cag cta tat gat aat taaatgaaac cgaaaagtta 4102Arg Asn Asn Lys Val Arg Gln Leu Tyr Asp Asn12351240aaaaagaaca ggtttttcaa agtgaaaata aaattacagt ttttttattg caatgattaa 4162cgtaacatct gcattacatt caagccgcac aaccccgcgg tgaccacccc tgacaggagt 4222aaacaatgtc aaagcaacag atcggcgtcg tcggtatggc agtgatggga cgcaacctcg 4282cgctcaacat cgaaagccgt ggttataccg tctctatttt caaccgttcc cgtgaaaaga 4342cggaagaagt tattgccgaa aatccaggca agaaactggt tccttactat acggtgaaag 4402agttcgttga atctcttgaa acgcctcgtc gcatcctgtt aatgggttaa agcaggtgca 4462ggcacggatg ctgctattga ttccctgaaa ccatatctcg ataaaggcga tatcatcatt 4522gatgggtggg taataccttc tttcaggaca ccattcgtcg taaccgcgag ctttctgcac 4582
aaggctttac ttcatcggta cc 4604<210>23<211>247<212>PRT<213>大肠杆菌<400>23Val Asp Asp Asn Leu Lys Gly Gln Gly Ala Gly Lys Asn Phe Leu Ser1 5 10 15Leu Ile Lys Tyr Ser Glu Thr Asp Tyr Thr Ile Tyr Cys Asp Gln Asp20 25 30Asp Ile Trp Leu Glu Asn Lys Ile Phe Glu Leu Val Lys Tyr Ala Asn35 40 45Glu Ile Lys Leu Asn Val Ser Asp Ala Pro Ser Leu Val Tyr Ala Asp50 55 60Gly Tyr Ala Tyr Met Asp Gly Glu Gly Thr Ile Asp Phe Ser Gly Ile65 70 75 80Ser Asn Asn His Ala Asp Gln Leu Lys Asp Phe Leu Phe Phe Asn Gly85 90 95Gly Tyr Gln Gly Cys Ser Ile Met Phe Asn Arg Ala Met Thr Lys Phe100 105 110Leu Leu Asn Tyr Arg Gly Phe Val Tyr Leu His Asp Asp Ile Thr Thr115 120 125Leu Ala Ala Tyr Ala Leu Gly Lys Val Tyr Phe Leu Pro Lys Tyr Leu130 135 140Met Leu Tyr Arg Gln His Thr Asn Ala Val Thr Gly Ile Lys Thr Phe145 150 155 160Arg Asn Gly Leu Thr Ser Lys Phe Lys Ser Pro Val Asn Tyr Leu Leu165 170 175Ser Arg Lys His Tyr Gln Val Lys Lys Ser Phe Phe Glu Cys Asn Ser180 185 190Ser Ile Leu Ser Glu Thr Asn Lys Lys Val Phe Leu Asp Phe Ile Ser195 200 205
Phe Cys Glu Ser Asn Asn Lys Phe Thr Asp Phe Phe Lys Leu Trp Arg210 215 220Gly Gly Phe Arg Leu Asn Asn Ser Arg Thr Lys Leu Leu Leu Lys Phe225 230 235 240Leu Ile Arg Arg Lys Phe Ser245<210>24<211>261<212>PRT<213>大肠杆菌<400>24Met Ile Ser Ile Leu Thr Pro Thr Phe Asn Arg Gln His Thr Leu Ser1 5 10 15Arg Leu Phe Asn Ser Leu Ile Leu Gln Thr Asp Lys Asp Phe Glu Trp20 25 30Ile Ile Ile Asp Asp Gly Ser Ile Asp Ala Thr Ala Val Leu Val Glu35 40 45Asp Phe Arg Lys Lys Cys Asp Phe Asp Leu Ile Tyr Cys Tyr Gln Glu50 55 60Asn Asn Gly Lys Pro Met Ala Leu Asn Ala Gly Val Lys Ala Cys Arg65 70 75 80Gly Asp Tyr Ile Phe Ile Val Asp Ser Asp Asp Ala Leu Thr Pro Asp85 90 95Ala Ile Lys Leu Ile Lys Glu Ser Ile His Asp Cys Leu Ser Glu Lys100 105 110Glu Ser Phe Ser Gly Val Gly Phe Arg Lys Ala Tyr Ile Lys Gly Gly115 120 125Ile Ile Gly Asn Asp Leu Asn Asn Ser Ser Glu His Ile Tyr Tyr Leu130 135 140Asn Ala Thr Glu Ile Ser Asn Leu Ile Asn Gly Asp Val Ala Tyr Cys145 150 155 160Phe Lys Lys Glu Ser Leu Val Lys Asn Pro Phe Pro Arg Ile Glu Asp
165 170 175Glu Lys Phe Val Pro Glu Leu Tyr Ile Trp Asn Lys Ile Thr Asp Lys180 185 190Ala Lys Ile Arg Phe Asn Ile Ser Lys Val Ile Tyr Leu Cys Glu Tyr195 200 205Leu Asp Asp Gly Leu Ser Lys Asn Phe His Asn Gln Leu Lys Lys Tyr210 215 220Pro Lys Gly Phe Lys Ile Tyr Tyr Lys Asp Gln Arg Lys Arg Glu Lys225 230 235 240Thr Tyr Ile Lys Lys Thr Lys Met Leu Ile Arg Tyr Leu Gln Cys Cys245 250 255Tyr Tyr Glu Lys Ile260<210>25<211>368<212>PRT<213>大肠杆菌<400>25Met Lys Ile Leu Phe Val Ile Thr Gly Leu Gly Leu Gly Gly Ala Glu1 5 10 15Lys Gln Val Cys Leu Leu Ala Asp Lys Leu Ser Leu Ser Gly His His20 25 30Val Lys Ile Ile Ser Leu Gly His Met Ser Asn Asn Lys Val Phe Pro35 40 45Ser Glu Asn Asn Val Asn Val Ile Asn Val Asn Met Ser Lys Asn Ile50 55 60Ser Gly Val Ile Lys Gly Cys Val Arg Ile Arg Asp Val Ile Ala Asn65 70 75 80Phe Lys Pro Asp Ile Val His Ser His Met Phe His Ala Asn Ile Ile85 90 95Thr Arg Leu Ser Val Ile Gly Ile Lys Asn Arg Pro Gly Ile Ile Ser100 105 110
Thr Ala His Asn Lys Asn Glu Gly Gly Tyr Phe Arg Met Leu Thr Tyr115 120 125Arg Ile Thr Asp Cys Leu Ser Asp Cys Cys Thr Asn Val Ser Lys Glu130 135 140Ala Val Asp Glu Phe Leu Arg Ile Lys Ala Phe Asn Pro Ala Lys Ala145 150 155 160Ile Thr Met Tyr Asn Gly Ile Asp Thr Asn Lys Phe Lys Phe Asp Leu165 170 175Leu Ala Arg Arg Glu Ile Arg Asp Gly Ile Asn Ile Lys Asn Asp Asp180 185 190Ile Leu Leu Leu Ala Ala Gly Arg Leu Thr Leu Ala Lys Asp Tyr Pro195 200 205Asn Leu Leu Asn Ala Met Thr Leu Leu Pro Glu His Phe Lys Leu Ile210 215 220Ile Ile Gly Asp Gly Glu Leu Arg Asp Glu Ile Asn Met Leu Ile Lys225 230 235 240Lys Leu Gln Leu Ser Asn Arg Val Ser Leu Leu Gly Val Lys Lys Asn245 250 255Ile Ala Pro Tyr Phe Ser Ala Cys Asp Ile Phe Val Leu Ser Ser Arg260 265 270Trp Glu Gly Phe Gly Leu Val Val Ala Glu Ala Met Ser Cys Glu Arg275 280 285Ile Val Val Gly Thr Asp Ser Gly Gly Val Arg Glu Val Ile Gly Asp290 295 300Asp Asp Phe Leu Val Pro Ile Ser Asp Ser Thr Gln Leu Ala Ser Lys305 310 315 320Ile Glu Lys Leu Ser Leu Ser Gln Ile Arg Asp His Ile Gly Phe Arg325 330 335Asn Arg Glu Arg Ile Leu Lys Asn Phe Ser Ile Asp Thr Ile Ile Met340 345 350Gln Trp Gln Glu Leu Tyr Gly Thr Ile Ile Cys Ser Lys His Glu Arg355 360 365
<210>26<211>367<212>PRT<213>大肠杆菌<400>26Met Thr Ala Arg Thr Thr Lys Val Leu His Leu Gln Leu Leu Pro Leu1 5 10 15Leu Ser Gly Val Gln Arg Val Thr Leu Asn Glu Ile Ser Ala Leu Tyr20 25 30Thr Asp Tyr Asp Tyr Thr Leu Val Cys Ser Lys Lys Gly Pro Leu Thr35 40 45Lys Ala Leu Leu Glu Tyr Asp Val Asp Cys His Cys Ile Pro Glu Leu50 55 60Thr Arg Glu Ile Thr Val Lys Asn Asp Phe Lys Ala Leu Phe Lys Leu65 70 75 80Tyr Lys Phe Ile Lys Lys Glu Lys Phe Asp Ile Val His Thr His Ser85 90 95Ser Lys Thr Gly Ile Leu Gly Arg Val Ala Ala Lys Leu Ala Arg Val100 105 110Gly Lys Val Ile His Thr Val His Gly Phe Ser Phe Pro Ala Ala Ser115 120 125Ser Lys Lys Ser Tyr Tyr Leu Tyr Phe Phe Met Glu Trp Ile Ala Lys130 135 140Phe Phe Thr Asp Lys Leu Ile Val Leu Asn Val Asp Asp Glu Tyr Ile145 150 155 160Ala Ile Asn Lys Leu Lys Phe Lys Arg Asp Lys Val Phe Leu Ile Pro165 170 175Asn Gly Val Asp Thr Asp Lys Phe Ser Pro Leu Glu Asn Lys Ile Tyr180 185 190Ser Ser Thr Leu Asn Leu Val Met Val Gly Arg Leu Ser Lys Gln Lys195 200 205Asp Pro Glu Thr Leu Leu Leu Ala Val Glu Lys Leu Leu Asn Glu Asn210 215 220
Val Asn Val Lys Leu Thr Leu Val Gly Asp Gly Glu Leu Lys Glu Gln225 230 235 240Leu Glu Ser Arg Phe Lys Arg Gln Asp Gly Arg Ile Ile Phe His Gly245 250 255Trp Ser Asp Asn Ile Val Asn Ile Leu Lys Val Asn Asp Leu Phe Ile260 265 270Leu Pro Ser Leu Trp Glu Gly Met Pro Leu Ala Ile Leu Glu Ala Leu275 280 285Ser Cys Gly Leu Pro Cys Ile Val Thr Asn Ile Pro Gly Asn Asn Ser290 295 300Leu Ile Glu Asp Gly Tyr Asn Gly Cys Leu Phe Glu Ile Arg Asp Cys305 310 315 320Gln Leu Leu Ser Gln Lys Ile Met Ser Tyr Val Gly Lys Pro Glu Leu325 330 335Ile Ala Gln Gln Ser Thr Asn Ala Arg Ser Phe Ile Leu Lys Asn Tyr340 345 350Gly Leu Val Lys Arg Asn Asn Lys Val Arg Gln Leu Tyr Asp Asn355 360 365<210>27<211>1272<212>DNA<213>大肠杆菌<220>
<221>CDS<222>(319)..(1269)<220>
<221>CDS<222>(3)..(215)<400>27cc ggg aag cac tcg gcg ctg att gtt gca cat cgt ctg acc acc gcg 47Gly Lys His Ser Ala Leu Ile Val Ala His Arg Leu Thr Thr Ala1 5 10 15
caa cgc tgc gat ctg att gcc gtt att gat aag ggg tta ctt gcg gaa95Gln Arg Cys Asp Leu Ile Ala Val Ile Asp Lys Gly Leu Leu Ala Glu20 25 30tac gga acc cac gaa cag ctg tta tct gcg ggc ggc ctc tat acc cgc143Tyr Gly Thr His Glu Gln Leu Leu Ser Ala Gly Gly Leu Tyr Thr Arg35 40 45tta tgg cat gac agc gtc agc agt act gct ctc cat cgc cag cac aac191Leu Trp His Asp Ser Val Ser Ser Thr Ala Leu His Arg Gln His Asn50 55 60atg aag gag gaa acc ccg gga tag ttactggaca cgtaatgtat taaaaacaca 245Met Lys Glu Glu Thr Pro Gly65 70gtcagaagcg gcggtaccgt gaatagccgc tttaattatt tatactgaca tccttaattt 305ttaaagagta tga atg ctg aac atg caa caa cat ctc tct gct atc gcc 354Met Leu Asn Met Gln Gln His Leu Ser Ala Ile Ala75 80agc ctg cgc aac caa ctg gca gcg ggc cac att gct aac ctt act gac402Ser Leu Arg Asn Gln Leu Ala Ala Gly His Ile Ala Asn Leu Thr Asp85 90 95ttc tgg cgc gaa gct gag tcg ctg aat gtt cct ctt gtg acg cca gtc450Phe Trp Arg Glu Ala Glu Ser Leu Asn Val Pro Leu Val Thr Pro Val100 105 110 115gaa gga gcg gaa gat gag cga gaa gtg acc ttt ctg tgg cgc gcc cga498Glu Gly Ala Glu Asp Glu Arg Glu Val Thr Phe Leu Trp Arg Ala Arg120 125 130cat cct ctg cag ggc gtt tat ctg cgt ctg aac cgg gtg acg gat aaa546His Pro Leu Gln Gly Val Tyr Leu Arg Leu Asn Arg Val Thr Asp Lys135 140 145gag cac gta gaa aaa gga atg atg agc gcc ctt ccc gaa acg gat atc594Glu His Val Glu Lys Gly Met Met Ser Ala Leu Pro Glu Thr Asp Ile150 155 160tgg aca ctg aca ctg cgt tta ccc gca agt tac tgc ggc tcc tat tcg642Trp Thr Leu Thr Leu Arg Leu Pro Ala Ser Tyr Cys Gly Ser Tyr Ser165 170 175ctg ctg gaa atc ccc ccc ggc act acg gct gag acg att gca ctg tcc690Leu Leu Glu Ile Pro Pro Gly Thr Thr Ala Glu Thr Ile Ala Leu Ser
180 185 190 195gga ggc cgt ttt gcc acc ctt gcc gga aag gcc gat ccg cta aac aaa738Gly Gly Arg Phe Ala Thr Leu Ala Gly Lys Ala Asp Pro Leu Asn Lys200 205 210atg ccg gag atc aac gtt cgg gga aac gca aag gaa tca gtg ctg aca786Met Pro Glu Ile Asn Val Arg Gly Asn Ala Lys Glu Ser Val Leu Thr215 220 225ctt gat aaa gct ccc gcc ctg tcg gaa tgg aac ggc ggc ttc cac acc834Leu Asp Lys Ala Pro Ala Leu Ser Glu Trp Asn Gly Gly Phe His Thr230 235 240gga caa ctg ctt acc tcc atg cgc att atc gcc ggg aaa tct cgc cag882Gly Gln Leu Leu Thr Ser Met Arg Ile Ile Ala Gly Lys Ser Arg Gln245 250 255gtt cgg ctc tat att ccg gat gtt gat att tct cag ccc ctc ggg ctg930Val Arg Leu Tyr Ile Pro Asp Val Asp Ile Ser Gln Pro Leu Gly Leu260 265 270 275gtc gtg ctg ccc gat ggt gaa acc tgg ttt gat cac ctt ggc gta tgc978Val Val Leu Pro Asp Gly Glu Thr Trp Phe Asp His Leu Gly Val Cys280 285 290gcg gca att gac gcc gcc ata aat aat ggg cgc atc gtg ccc gtg gct1026Ala Ala Ile Asp Ala Ala Ile Asn Asn Gly Arg Ile Val Pro Val Ala295 300 305gta ctg ggc att gac aac att aat gaa cat gaa cgc act gag ata ctc1074Val Leu Gly Ile Asp Asn Ile Asn Glu His Glu Arg Thr Glu Ile Leu310 315 320ggc ggg cgc agc aaa ctg ata aag gat atc gcc gga cat ctg ctg ccg1122Gly Gly Arg Ser Lys Leu Ile Lys Asp Ile Ala Gly His Leu Leu Pro325 330 335atg att cgc gct gaa caa ccg cag cgt cag tgg gca gac cgt tcg cgc1170Met Ile Arg Ala Glu Gln Pro Gln Arg Gln Trp Ala Asp Arg Ser Arg340 345 350 355aca gtg ctg gcc ggg cag agc ctc ggc ggg atc agt gcg cta atg ggg1218Thr Val Leu Ala Gly Gln Ser Leu Gly Gly Ile Ser Ala Leu Met Gly360 365 370gct cgt tac gca ccg gaa acg ttc ggt ctg gtg ctc agc cac tct cct1266Ala Arg Tyr Ala Pro Glu Thr Phe Gly Leu Val Leu Ser His Ser Pro
375 380 385caa tgc1272Gln<210>28<211>70<212>PRT<213>大肠杆菌<400>28Gly Lys His Ser Ala Leu Ile Val Ala His Arg Leu Thr Thr Ala Gln1 5 10 15Arg Cys Asp Leu Ile Ala Val Ile Asp Lys Gly Leu Leu Ala Glu Tyr20 25 30Gly Thr His Glu Gln Leu Leu Ser Ala Gly Gly Leu Tyr Thr Arg Leu35 40 45Trp His Asp Ser Val Ser Ser Thr Ala Leu His Arg Gln His Asn Met50 55 60Lys Glu Glu Thr Pro Gly65 70<210>29<211>317<212>PRT<213>大肠杆菌<400>29Met Leu Asn Met Gln Gln His Leu Ser Ala Ile Ala Ser Leu Arg Asn1 5 10 15Gln Leu Ala Ala Gly His Ile Ala Asn Leu Thr Asp Phe Trp Arg Glu20 25 30Ala Glu Ser Leu Asn Val Pro Leu Val Thr Pro Val Glu Gly Ala Glu35 40 45Asp Glu Arg Glu Val Thr Phe Leu Trp Arg Ala Arg His Pro Leu Gln50 55 60Gly Val Tyr Leu Arg Leu Asn Arg Val Thr Asp Lys Glu His Val Glu65 70 75 80
Lys Gly Met Met Ser Ala Leu Pro Glu Thr Asp Ile Trp Thr Leu Thr85 90 95Leu Arg Leu Pro Ala Ser Tyr Cys Gly Ser Tyr Ser Leu Leu Glu Ile100 105 110Pro Pro Gly Thr Thr Ala Glu Thr Ile Ala Leu Ser Gly Gly Arg Phe115 120 125Ala Thr Leu Ala Gly Lys Ala Asp Pro Leu Asn Lys Met Pro Glu Ile130 135 140Asn Val Arg Gly Asn Ala Lys Glu Ser Val Leu Thr Leu Asp Lys Ala145 150 155 160Pro Ala Leu Ser Glu Trp Asn Gly Gly Phe His Thr Gly Gln Leu Leu165 170 175Thr Ser Met Arg Ile Ile Ala Gly Lys Ser Arg Gln Val Arg Leu Tyr180 185 190Ile Pro Asp Val Asp Ile Ser Gln Pro Leu Gly Leu Val Val Leu Pro195 200 205Asp Gly Glu Thr Trp Phe Asp His Leu Gly Val Cys Ala Ala Ile Asp210 215 220Ala Ala Ile Asn Asn Gly Arg Ile Val Pro Val Ala Val Leu Gly Ile225 230 235 240Asp Asn Ile Asn Glu His Glu Arg Thr Glu Ile Leu Gly Gly Arg Ser245 250 255Lys Leu Ile Lys Asp Ile Ala Gly His Leu Leu Pro Met Ile Arg Ala260 265 270Glu Gln Pro Gln Arg Gln Trp Ala Asp Arg Ser Arg Thr Val Leu Ala275 280 285Gly Gln Ser Leu Gly Gly Ile Ser Ala Leu Met Gly Ala Arg Tyr Ala290 295 300Pro Glu Thr Phe Gly Leu Val Leu Ser His Ser Pro Gln305 310 315
<210>30<211>4039<212>DNA<213>大肠杆菌<220>
<221>CDS<222>(1)..(285)<220>
<221>CDS<222>(370)..(1326)<400>30cct tca atg tgg tgg acg cca gaa aga acc agt cga cca ggc ttg ttc48Pro Ser Met Trp Trp Thr Pro Glu Arg Thr Ser Arg Pro Gly Leu Phe1 5 10 15agc gaa acc gat acc tca tgg gtg agt gag cat ctg ctt tct gcc cca96Ser Glu Thr Asp Thr Ser Trp Val Ser Glu His Leu Leu Ser Ala Pro20 25 30ccg cag ggc gta cgt atc agc ctg tgc gtg gga tcg ctg gaa ggt tcg144Pro Gln Gly Val Arg Ile Ser Leu Cys Val Gly Ser Leu Glu Gly Ser35 40 45aca gtg cct cac gtt cag cag ctt cac cag cgg ctg att acc gct ggc192Thr Val Pro His Val Gln Gln Leu His Gln Arg Leu Ile Thr Ala Gly50 55 60gtc gaa agc cat tgc gca atc tac acc ggt ggt cac gat tac gca tgg240Val Glu Ser His Cys Ala Ile Tyr Thr Gly Gly His Asp Tyr Ala Trp65 70 75 80tgg cgc ggt gca ctg att gac ggg att ggt tta cta cag ggt tga285Trp Arg Gly Ala Leu Ile Asp Gly Ile Gly Leu Leu Gln Gly85 90 95gttgacccac aaacactttc aggaaacggt acagacttcc tgaataaatc aaatagtcac 345ctgcggaaaa ggaataatca tcag atg tat gcc cgc gag tat cgc tca aca 396Met Tyr Ala Arg Glu Tyr Arg Ser Thr100cgc ccg cat aaa gcg att ttc ttt cat ctt tct tgc ctc acc ctt atc444Arg Pro His Lys Ala Ile Phe Phe His Leu Ser Cys Leu Thr Leu Ile105 110 115 120
tgt agt gcg caa gtt tat gcg aag ccg gat atg cgg cca ctg ggg ccg492Cys Ser Ala Gln Val Tyr Ala Lys Pro Asp Met Arg Pro Leu Gly Pro125 130 135aat ata gcc gat aaa ggc tcc gtg ttt tac cat ttc agc gtc acc tct540Asn Ile Ala Asp Lys Gly Ser Val Phe Tyr His Phe Ser Val Thr Ser140 145 150ttc gac tct gtc gat ggc aca cgc cat tat cgg gta tgg acg gcc gtg588Phe Asp Ser Val Asp Gly Thr Arg His Tyr Arg Val Trp Thr Ala Val155 160 165ccg aat aca acc gca ccg gca tcg ggt tac ccg att tta tat atg ctt636Pro Asn Thr Thr Ala Pro Ala Ser Gly Tyr Pro Ile Leu Tyr Met Leu170 175 180gac ggt aac gca gtt atg gat cgc ctg gat gac gaa ctg ctc aaa caa684Asp Gly Asn Ala Val Met Asp Arg Leu Asp Asp Glu Leu Leu Lys Gln185 190 195 200ttg tca gaa aaa aca ccg cca gtg atc gtg gct gtc ggg tat cag acc732Leu Ser Glu Lys Thr Pro Pro Val Ile Val Ala Val Gly Tyr Gln Thr205 210 215aac ctc cct ttc gat ctc aac agc agg gct tac gac tat acg cca gca780Asn Leu Pro Phe Asp Leu Asn Ser Arg Ala Tyr Asp Tyr Thr Pro Ala220 225 230gca gaa agc aga aaa aca gat ctc cac tca ggg cgt ttt agc cgt aag828Ala Glu Ser Arg Lys Thr Asp Leu His Ser Gly Arg Phe Ser Arg Lys235 240 245agt ggt ggc agc aac aac ttc cgc cag tta ctg gaa acg cgt att gcc876Ser Gly Gly Ser Asn Asn Phe Arg Gln Leu Leu Glu Thr Arg Ile Ala250 255 260cca aaa gtg gaa cag gga ctg aat atc gat cgg caa cgc cgc ggc tta924Pro Lys Val Glu Gln Gly Leu Asn Ile Asp Arg Gln Arg Arg Gly Leu265 270 275 280tgg ggg cac tcc tac ggc ggc ctc ttc gtg ctg gat tcc tgg ctg tcc972Trp Gly His Ser Tyr Gly Gly Leu Phe Val Leu Asp Ser Trp Leu Ser285 290 295tcc tct tac ttc cgg tcg tac tac agc gcc agc ccg tcg ttg ggc aga1020Ser Ser Tyr Phe Arg Ser Tyr Tyr Ser Ala Ser Pro Ser Leu Gly Arg300 305 310
ggt tat gat gct ttg cta agc cgc gtt acg gcg gtt gag cct ctg caa1068Gly Tyr Asp Ala Leu Leu Ser Arg Val Thr Ala Val Glu Pro Leu Gln315 320 325ttc tgc gcc aaa cac ctg gcg ata atg gaa ggc tcg gcg aca cag ggt1116Phe Cys Ala Lys His Leu Ala Ile Met Glu Gly Ser Ala Thr Gln Gly330 335 340gat aac cgg gaa acg cat gct gtc ggg gtg ctg tcg aaa att cat acc1164Asp Asn Arg Glu Thr His Ala Val Gly Val Leu Ser Lys Ile His Thr345 350 355 360acc ctc act ata ctg aaa gat aaa ggc gtc aat gcc gta ttt tgg gat1212Thr Leu Thr Ile Leu Lys Asp Lys Gly Val Asn Ala Val Phe Trp Asp365 370 375ttc ccc aac ctg gga cac ggg ccg atg ttc aat gcc tcc ttt cgc cag1260Phe Pro Asn Leu Gly His Gly Pro Met Phe Asn Ala Ser Phe Arg Gln380 385 390gca ctg tta gat atc agt ggt gaa aac gca aat tac aca gca ggt tgt1308Ala Leu Leu Asp Ile Ser Gly Glu Asn Ala Asn Tyr Thr Ala Gly Cys395 400 405cat gag tta agc cac taa acactgcccg cttttacgcg ggcagtacgc 1356His Glu Leu Ser His410ctgaaacact acgatcagaa tgatgcggta actccggcat agtaagcccg gcctggctcg 1416ttataggtat tcgccccttc agaagatcgg aagatctgtt tattgaggat attactgacg 1476ccgacattaa gacgcagatt tttattaata tcgtaattga agttcgtccc caccagtgaa 1536taagcgccca gctctttacc tgacagaccg ccagtatctt cactgcgggt ttccgcatga 1596gtacgcggtt tttgtctgcc atataacgtc cagttgacgc tggcagaaaa cgcctgggtg 1656atggtccagt taagcgagtt attgatagta tatttcggga tgaccgacag aggattaccg 1716gtgtcttttt gctccgaagt gatcatccat gtggcattgg tattccagtt cagacgatct 1776ttcaccagtg ggaaagacat actggcttcg ataccgtcca ccagagcttt cccgccattc 1836tgccacttga ggatatatgc gcctgaagcg gtttgcccga taacgttatc cccggccacg 1896atcttattct ggtaatcatt gcggaagtag gtcacacttg cgtggtaatc ttcccaggtg 1956
aactccagcc caatttcttt attgacgctg atttccggat cgagatcttt attaccgatc 2016aggtagcacc cgcctgatgt aatatctttt ggacagccat tgcctttcga gtagagcaga 2076tagccttcac tggattgata caggtttggg gctttaaagg ttcgggcaac ccctgctttg 2136actttgaaat aatcgcccaa ttcctgcgaa agattcagac tggggctgaa gttcccgccg 2196gagtcgctga gataatcaaa gcgcaggccg ggaatgatat tcgtgccagg aaccggctca 2256atgttatctt caatatacag cgcactgatt tgagaatgat ttttactgct gcgatccgca 2316gcagagccag aaataccgct gatatcactg tcattcaccg tcaggctggt agaggaagga 2376tcatcgagct tatcgcggtt ccactctgca ccaacggtca gcgtttgatc aaccatcaca 2436ttcaaaggaa tattaagctc gccgctggtt cgccaggaac tcaggcgatt ggtcgtaaac 2496ttttcacccg ctaaaatacg cccttcacca ccgccggata atccttcatt catgcgggta 2556ttattggttt tctcgtaata aacaccaaag cgactttgtc cccagtccca gataccatta 2616tgcgtaatgc cataattctg tcggtacagg cggctcgtct cttgtgccgg attttgccag 2676gcttttcggt aactgcactg gaagaactgt tttgcgtatc gccgcataga tattcccctg 2736gcggctatat ccggcttcga aatcgagaat ctgctgcgga tttaatttcc acgagacaac 2796gccgttaata tctttgttac gtaccccttc atgcccggct gcgtttttcg taccgaccgg 2856agaattaata tcccaactgt cagcatccgt tttattcaga ttaccataca aacgcgtggt 2916aagagcatta ccagccagag gcccactaag gctgaaattg gcgcgacgcg tagcgccctc 2976atcgctactt tccggctgat tggtgtataa cgacagcgaa ccgtgccagt cgttggtggg 3036acgtttggta atgatgttca ccaccccccc ggctgccccc gaaccgtagc gcgccgccgc 3096agggccgcgg atcacttcaa tacgctcaac ctgttccggt ggcacccagt tggtgtcacc 3156gcgggtatca cgctctccac gccagctata acgcacggag ttacgtgacg tcaccggtac 3216accatcaatt aaaattaagg tgttttccgg ccccatacca cgaatatcga tctggcggtt 3276gttaccgcgt gtgcccgagg cgctattgcc ggtaagattg acgccaggca ttttacgaat 3336aatatctgaa aggtcgttta ccggaggggt ctttttaata tcctcgctgg taataaccga 3396
cacgcccggc tgctgtttta atacctgctc agcggtggct tccaccacca gagtctcgtc 3456attatcatcg tcggaggatt tggctactga tacctggcta ttcaacccaa ccaggagcac 3516agttagcgac cagaggattt tgttaattct catacctatt ccctaataaa tgcctaactt 3576aaaatgtttg atcgttaagc tcacatcctt gccagatatt ttttactgcc attattgttt 3636ttatataaga atgataatta atatcattta gcaaaagaaa aagcaatccc tcacaagata 3696aatatatcga tttttcataa atatcaaatt gatatataac atatgttttt tatttcattg 3756tacttcagtc aaataaattt ctgaagcact gctagtagtg ccagttcagc tttctttttg 3816actcattccg gcaaagtcag taccgttcat cttttgtact gatgttgcca ctggaaaatc 3876ggtgcgcttg tcgatcatcg ggaattttgt cacaatttct aacggatagt gttcacattg 3936tttctaacct gcattttcag acacgggcgc tgcttatgta tataagatca gcatcactag 3996gtctttctgc aacactactg ctttcaacaa ggtcaggcat ttc 4039<210>31<211>94<212>PRT<213>大肠杆菌<400>31Pro Ser Met Trp Trp Thr Pro Glu Arg Thr Ser Arg Pro Gly Leu Phe1 5 10 15Ser Glu Thr Asp Thr Ser Trp Val Ser Glu His Leu Leu Ser Ala Pro20 25 30Pro Gln Gly Val Arg Ile Ser Leu Cys Val Gly Ser Leu Glu Gly Ser35 40 45Thr Val Pro His Val Gln Gln Leu His Gln Arg Leu Ile Thr Ala Gly50 55 60Val Glu Ser His Cys Ala Ile Tyr Thr Gly Gly His Asp Tyr Ala Trp65 70 75 80Trp Arg Gly Ala Leu Ile Asp Gly Ile Gly Leu Leu Gln Gly85 90
<210>32<211>318<212>PRT<213>大肠杆菌<400>32Met Tyr Ala Arg Glu Tyr Arg Ser Thr Arg Pro His Lys Ala Ile Phe1 5 10 15Phe His Leu Ser Cys Leu Thr Leu Ile Cys Ser Ala Gln Val Tyr Ala20 25 30Lys Pro Asp Met Arg Pro Leu Gly Pro Asn Ile Ala Asp Lys Gly Ser35 40 45Val Phe Tyr His Phe Ser Val Thr Ser Phe Asp Ser Val Asp Gly Thr50 55 60Arg His Tyr Arg Val Trp Thr Ala Val Pro Asn Thr Thr Ala Pro Ala65 70 75 80Ser Gly Tyr Pro Ile Leu Tyr Met Leu Asp Gly Asn Ala Val Met Asp85 90 95Arg Leu Asp Asp Glu Leu Leu Lys Gln Leu Ser Glu Lys Thr Pro Pro100 105 110Val Ile Val Ala Val Gly Tyr Gln Thr Asn Leu Pro Phe Asp Leu Asn115 120 125Ser Arg Ala Tyr Asp Tyr Thr Pro Ala Ala Glu Ser Arg Lys Thr Asp130 135 140Leu His Ser Gly Arg Phe Ser Arg Lys Ser Gly Gly Ser Asn Asn Phe145 150 155 160Arg Gln Leu Leu Glu Thr Arg Ile Ala Pro Lys Val Glu Gln Gly Leu165 170 175Asn Ile Asp Arg Gln Arg Arg Gly Leu Trp Gly His Ser Tyr Gly Gly180 185 190Leu Phe Val Leu Asp Ser Trp Leu Ser Ser Ser Tyr Phe Arg Ser Tyr195 200 205Tyr Ser Ala Ser Pro Ser Leu Gly Arg Gly Tyr Asp Ala Leu Leu Ser210 215 220
Arg Val Thr Ala Val Glu Pro Leu Gln Phe Cys Ala Lys His Leu Ala225 230 235 240Ile Met Glu Gly Ser Ala Thr Gln Gly Asp Asn Arg Glu Thr His Ala245 250 255Val Gly Val Leu Ser Lys Ile His Thr Thr Leu Thr Ile Leu Lys Asp260 265 270Lys Gly Val Asn Ala Val Phe Trp Asp Phe Pro Asn Leu Gly His Gly275 280 285Pro Met Phe Asn Ala Ser Phe Arg Gln Ala Leu Leu Asp Ile Ser Gly290 295 300Glu Asn Ala Asn Tyr Thr Ala Gly Cys His Glu Leu Ser His305 310 315<210>33<211>3292<212>DNA<213>大肠杆菌<400>33ccgctgcggt tgattgccgg atgcggcgtg aacgccttat ccggcctaca atcattgcaa 60attcaataaa ttgcagcgtt ctgtaggctg gataagatgc gtcagcatcg catccggcaa 120aggcagatct cagcgatagc gccggcttag tcagatttaa tctgcgcgcg tggtggatat 180tttttcagga tctccatata cgcgtgcatt tcggtctgta gcggtacacc catcggaata 240tggcgcacgc cgatagagtc gctttcctgc ggatcggtgt acaggttaaa caccgacgat 300cccgccgttt gcattactgt gccggtgaat ccaccctgat atccgctctg ggtataagcg 360taaggttgct gaatcaggac gtgatacttg aactcatcca tacgcacagc agaaagttta 420ccgttgagga agtagtgctc ggccttacgg ttagactgac catttgttcc caggaagaaa 480gatgtctggt ccacaccatc gataaaggtg gttttcggta ctaaattcgc tactttcgcc 540ccaggatgcc ccgccagatc cagcgccgta gggaagagat ccgccagatc gacaatgccg 600tcagatttac gcggttggat catgcctttc cagtaaacga aggttggcac acgaacgccg 660ccttcccatg tagaaccttt cgcaccgcgg aacggcgtgc gaccgtgcgg cggaacttcg 720gcttccggac cgttatcaga ggtgaacaca atcagcgtgt tatcaagctg accgtttttc 780tccagtgctt tatacagatt ggcgaagata tcgttcatct ccaccatgca gtcgccgtaa 840gaggtgcgcg ccggagagct acccgcatat ttggcgttcg ggtagttatc gaagtgacag 900ccgcgagtgc cgtaatagag gaagaaaggc ttatcactct tcgccatctt gtcgaggaac 960ttaacgccat attccatcca gcgttgatcc aggtcttcca tatatttcgg cgtaatgtcg 1020gcaatggctt cctgttcacc gccgcgcacg gcatgaacgt catctttgct gaacggcagt 1080ttttggatgt attcagaacg agccgggctc agggcgactt ccgggttgac atgaacatca 1140cgccattcgg tatacatatc ggacaccgag ttaaagccgc ggaaatcatc aaagccaacg 1200ttctgcggct gcgactcttt gttttccccc atatgccatt tcccgatagc ctgggtgacg 1260tagccctgat cgtgcagcaa ctgcggcagc gtggttaacc cttgcagacc gcccggttgc 1320
ccgtacattg gcggcatcag aatgccgtgg tggatggagt attgtccggt gagaatcgtg 1380gcgcgggttg gggaagaact cggttgagaa tacgccgaag ttaaaatcag cccctggctg 1440gcaacggcgt cgatatctgg tgtagggtta cccaccgcca cgccgccgcc gttaaagcca 1500acgtccatcc agcccacatc atccagcaag aaaacaacca cgttcggttt cttaccggtt 1560tttttctcaa gttccgccag tttctgctgg gtttctttgt cttgtgcagg atgctgcatc 1620accggcatca tgttgtcggc aatagtggtc gccggtttaa ccagatactg gtttgggtga 1680tcgtatccgg caaagccttt gcgtgcggtg gcggttgacg gggtatctgc tgcgctggct 1740atgagaggaa gagctgcggc gacagcaaca acaagaagtt tgggtgaaaa cgaaaattcc 1800atgcaaaatg ctccggtttc atgtcgtcaa aatgatgacg taattaagca ttgataattg 1860agatccctct ccctgacagg atgattgcat aaataatagt gataaaaata aattatttat 1920ttatccagaa atgaattgaa aaatcaggag agcattttca atcctacctc tggcgcaggt 1980gatattgtaa ggcggtgatg ttatatcgcg ttgattattg atgctgtttt tagttttaac 2040ggcattaata tatatgttat taattgaatg acttttatta ttcattatat atatgtgtag 2100aattgtgcgc aggagaaata ttcactcagg aagttattac tcaggaagca aagaggatta 2160cagaattatc tcataacaag tgttaaggga tgttatttcc cggttctctg tggcataata 2220aacgagtaga tgctcattcc atctcttatg ttcgccttag tgcctcataa actccggaat 2280gacgcagagc cgtttacggt gcttatcgtc cactgacaga tgtcgcttat gcctcatcag 2340acaccatgga cacaacgttg agtgaagcac ccacttgttg tcatacagac ctgttttaac 2400gcctgctccg taataagagc aggcgttttt ttatatatca gaaaggcccc ggaggtgctt 2460gcctccgggt gagaaagagc tactgtggcg ggttgttctg caacgttaac atcaaaccgt 2520cgcgacgcat cgctgcggct tcttccggct tgtgcagtct gtccagcgcg tcggcaagcc 2580atgcgtaatc gtaggcgtcc ggacgttgtt tcagcgctgc gcggaaggcg agcgatgctt 2640cctgccattc tccgtgtttc atcagcgact gacccagtgt gctccacaac agcgggcgat 2700cgcccacgtt tttgatctgt tggcgcagca ctttttccaa gctgttcccg ggttaattgg 2760gttttcagac gccggggatc ggcagcagca ggccgaatcg tcatactggc gtttcaggcc 2820atcgatgata atttgctggg cagtatcatg atcgtcacac tcaataagat gttccgccat 2880tgccacctgc aaggccacct gatgacgcgt tttccggctt tggtttttcc accagttacg 2940caaaccttca ctaccgttat cggcacgcgc ctgatccatc aggccaatcc atgcctgttg 3000ttccagcatt gcacgatgtt cttcatcacc aacatgggct ttcgccattg atgggatgat 3060atccagcagc gaactccatg caccagtgcg gatatacgcc tgttccgcca gacgtaatac 3120ttccggatgg cgtggcgtaa cttccagcag cttatccacg ccgtgacgtg ctgcatggtt 3180ttcattacgg gccagttgca gacgtacacg ggtgatttct accggaatgg tgtcattgcc 3240ggccagctcc gctgcgcgtt ccagatgttg gttggcgcgt gcttcagcat cc 3292<210>34<211>11165<212>DNA<213>大肠杆菌<220>
<221>CDS<222>(3791)..(4834)<220>
<221>CDS<222>(10459)..(10776)
<220>
<221>CDS<222>(10134)..(10427)<220>
<221>CDS<222>(9836)..(10081)<220>
<221>CDS<222>(7816)..(9480)<220>
<221>CDS<222>(4878)..(7802)<220>
<221>CDS<222>(3460)..(3702)<220>
<221>CDS<222>(3054)..(3407)<220>
<221>CDS<222>(2613)..(3041)<220>
<221>CDS<222>(2198)..(2530)<220>
<221>CDS<222>(1939)..(2196)<220>
<221>CDS<222>(1573)..(1893)<220>
<221>CDS<222>(1102)..(1485)<220>
<221>CDS<222>(2)..(1099)
<400>34c agc gat atg cag cgc ggt atc cag gct gca acg gct gca ctt cag ggc 49Ser Asp Met Gln Arg Gly Ile Gln Ala Ala Thr Ala Ala Leu Gln Gly1 5 10 15ctg gtg ggc ggc aat atg gca ggc gcg ctg gca ggt gct tca gcg ccg97Leu Val Gly Gly Asn Met Ala Gly Ala Leu Ala Gly Ala Ser Ala Pro20 25 30gag ctg gcg aac atc atc ggt cat cac gcg ggt att gat gac aat aca145Glu Leu Ala Asn Ile Ile Gly His His Ala Gly Ile Asp Asp Asn Thr35 40 45gcg gca aaa gcc att gcc cat gcc att ctc ggt ggt gtg aca gca gcc193Ala Ala Lys Ala Ile Ala His Ala Ile Leu Gly Gly Val Thr Ala Ala50 55 60ctt cag ggc aac agt gcg gca gca ggc gca att ggt gcg ggt act ggt241Leu Gln Gly Asn Ser Ala Ala Ala Gly Ala Ile Gly Ala Gly Thr Gly65 70 75 80gaa gtg atc gcg tca gcc att gcg aaa agc ctc tac ccg ggc gta gat289Glu Val Ile Ala Ser Ala Ile Ala Lys Ser Leu Tyr Pro Gly Val Asp85 90 95ccg tcg aaa ctg aca gaa gat cag aag caa act gta agc acg ctg gca337Pro Ser Lys Leu Thr Glu Asp Gln Lys Gln Thr Val Ser Thr Leu Ala100 105 110acg ctg tca gcg ggt atg gcc ggc ggc att gcc agt ggc gat gtg gct385Thr Leu Ser Ala Gly Met Ala Gly Gly Ile Ala Ser Gly Asp Val Ala115 120 125ggc gcg gct gct gga gct ggt gcc ggg aag aac gtt gtt gag aat aat433Gly Ala Ala Ala Gly Ala Gly Ala Gly Lys Asn Val Val Glu Asn Asn130 135 140gcg ctg agt ctg gtt gcc aga ggc tgt gcg gtc gca gca cct tgc agg481Ala Leu Ser Leu Val Ala Arg Gly Cys Ala Val Ala Ala Pro Cys Arg145 150 155 160act aaa gtt gca gag cag ttg cta gaa atc ggg gcg aaa gcg ggc atg529Thr Lys Val Ala Glu Gln Leu Leu Glu Ile Gly Ala Lys Ala Gly Met165 170 175gcc ggg ctt gcc ggg gcg gca gtc aag gat atg gcc gac agg atg acc577Ala Gly Leu Ala Gly Ala Ala Val Lys Asp Met Ala Asp Arg Met Thr180 185 190
tcc gat gaa ctg gag cat ctg att acc ctg caa atg atg ggt aat gat625Ser Asp Glu Leu Glu His Leu Ile Thr Leu Gln Met Met Gly Asn Asp195 200 205gag atc act act aag tat ctc agt tcg ttg cat gat aag tac ggt tcc673Glu Ile Thr Thr Lys Tyr Leu Ser Ser Leu His Asp Lys Tyr Gly Ser210 215 220ggg gct gcc tcg aat ccg aat atc ggt aaa gat ctg acc gat gcg gaa721Gly Ala Ala Ser Asn Pro Asn Ile Gly Lys Asp Leu Thr Asp Ala Glu225 230 235 240aaa gta gaa ctg ggc ggt tcc ggc tca gga acc ggt aca cca cca cca769Lys Val Glu Leu Gly Gly Ser Gly Ser Gly Thr Gly Thr Pro Pro Pro245 250 255tcg gaa aat gat cct aag cag caa aat gaa aaa act gta gat aag ctt817Ser Glu Asn Asp Pro Lys Gln Gln Asn Glu Lys Thr Val Asp Lys Leu260 265 270aat cag aag caa gaa agt gcg att aag aag atc gat aac act ata aaa865Asn Gln Lys Gln Glu Ser Ala Ile Lys Lys Ile Asp Asn Thr Ile Lys275 280 285aat gct ctg aaa gat cat gat att att gga act ctc aag gat atg gat913Asn Ala Leu Lys Asp His Asp Ile Ile Gly Thr Leu Lys Asp Met Asp290 295 300ggt aag cca gtt cct aaa gag aat gga gga tat tgg gat cat atg cag961Gly Lys Pro Val Pro Lys Glu Asn Gly Gly Tyr Trp Asp His Met Gln305 310 315 320gaa atg caa aat acg ctc aga gga tta aga aat cat gcg gat acg ttg1009Glu Met Gln Asn Thr Leu Arg Gly Leu Arg Asn His Ala Asp Thr Leu325 330 335aaa aac gtc aac aat cct gaa gct cag gct gcg tat ggc aga gca aca1057Lys Asn Val Asn Asn Pro Glu Ala Gln Ala Ala Tyr Gly Arg Ala Thr340 345 350gat gct att aat aaa ata gaa tca gcc ttg aaa gga tat gga at atg 1104Asp Ala Ile Asn Lys Ile Glu Ser Ala Leu Lys Gly Tyr GlyMet355 360 365att acc tta cgt aaa ttg att gga aac atc aat atg aca aaa gag cct1152Ile Thr Leu Arg Lys Leu Ile Gly Asn Ile Asn Met Thr Lys Glu Pro370 375 380
gag caa caa tca ccg ctt gaa ctc tgg ttc gaa cgt atc ata gat gtg1200Glu Gln Gln Ser Pro Leu Glu Leu Trp Phe Glu Arg Ile Ile Asp Val385 390 395cct ctt gaa aag tta aca gtg gaa gat ctt tgc cgc gct atc cga caa1248Pro Leu Glu Lys Leu Thr Val Glu Asp Leu Cys Arg Ala Ile Arg Gln400 405 410 415aat tta tgt att gat cag ttg atg cca aga gtg ttg gaa gtt cta act1296Asn Leu Cys Ile Asp Gln Leu Met Pro Arg Val Leu Glu Val Leu Thr420 425 430aaa gag ccg tta gcg ggt gaa tat tac gat ggt gaa cta att gca gct1344Lys Glu Pro Leu Ala Gly Glu Tyr Tyr Asp Gly Glu Leu Ile Ala Ala435 440 445tta tca acg ata aaa gga gaa gat cta aaa gat cag aaa agt acc ttt1392Leu Ser Thr Ile Lys Gly Glu Asp Leu Lys Asp Gln Lys Ser Thr Phe450 455 460acc caa aga agg caa ctt ata aac cag cta gaa ccg tca gat att aac1440Thr Gln Ile Arg Gln Leu Ile Asn Gln Leu Glu Pro Ser Asp Ile Asn465 470 475gat gat tta aga aaa gat ata tta aaa atc aat cag ata att gta1485Asp Asp Leu Arg Lys Asp Ile Leu Lys Ile Asn Gln Ile Ile Val480 485 490taactaatcc cggccactga gccgagagct tctttgtgtg ccgggcatgt tcagcagctt 1545gggggtgaaa gtcccctgtc cagcctg atg gtg gcg aag gcg ttc gcg tac gca 1599Met Val Ala Lys Ala Phe Ala Tyr Ala495 500ctt aac cag tgg ccg gca ctg acg tac tat gcg aac gat ggc tgg gtg1647Leu Asn Gln Trp Pro Ala Leu Thr Tyr Tyr Ala Asn Asp Gly Trp Val505 510 515gaa atc gac aac aac atc gct gaa aat gcc ctg cgg gcg gtc agt ctg1695Glu Ile Asp Asn Asn Ile Ala Glu Asn Ala Leu Arg Ala Val Ser Leu520 525 530 535ggt cgt aaa aac ttc ctg ttc ttc ggc tct gac cat ggt ggt gag cgg1743Gly Arg Lys Asn Phe Leu Phe Phe Gly Ser Asp His Gly Gly Glu Arg540 545 550gga gcg cta ctg tac agc ctg atc ggg acg tgc aaa ctg aat gac gtg1791
Gly Ala Leu Leu Tyr Ser Leu Ile Gly Thr Cys Lys Leu Asn Asp Val555 560 565gat cca gaa agc tac ctt cgc cat gtg ctt gcc gtc ata gca gac tgg1839Asp Pro Glu Ser Tyr Leu Arg His Val Leu Ala Val Ile Ala Asp Trp570 575 580ccg gtc aac cgg gtc agc gaa ctg ctt ccg tgg cgc ata gca ctg cca1887Pro Val Asn Arg Val Ser Glu Leu Leu Pro Trp Arg Ile Ala Leu Pro585 590 595gct gaa taacacatcc ccgtcaatac ggccctcgct gtacgcttac agaaa atg ctg 1944Ala Glu Met Leu600atg tct gta cag aaa gaa aag aac gtc gca gag agt gtg gta tct gaa1992Met Ser Val Gln Lys Glu Lys Asn Val Ala Glu Ser Val Val Ser Glu605 610 615acg cat acc ggc gac agc gta tat gct tcc ctg ttt gaa aaa att aac2040Thr His Thr Gly Asp Ser Val Tyr Ala Ser Leu Phe Glu Lys Ile Asn620 625 630 635ctg aat ccg gta tct gcc ctg agt gca ctg gat aac cct ttc cgg tca2088Leu Asn Pro Val Ser Ala Leu Ser Ala Leu Asp Asn Pro Phe Arg Ser640 645 650gca gat aac gcg act ggc aga att acc tcc agc ata caa cct gcg gtg2136Ala Asp Asn Ala Thr Gly Arg Ile Thr Ser Ser Ile Gln Pro Ala Val655 660 665cag tgc gca gct gct gca gca act gag ggt tct tgt ccc cgg caa tcc2184Gln Cys Ala Ala Ala Ala Ala Thr Glu Gly Ser Cys Pro Arg Gln Ser670 675 680ccg tgt tca gga a atg gtg gat aac tgg cag aag agt gta agg agt cgt 2233Pro Cys Ser Gly Met Val Asp Asn Trp Gln Lys Ser Val Arg Ser Arg685 690 695gcg ctc ccg gaa gag gcg atg acg ggc tgg aac gaa ggc atg atc cgc2281Ala Leu Pro Glu Glu Ala Met Thr Gly Trp Asn Glu Gly Met Ile Arg700 705 710 715tta cag cag ttg gct gag cgc ctg aac cgt cag gat gaa cag cgg gga2329Leu Gln Gln Leu Ala Glu Arg Leu Asn Arg Gln Asp Glu Gln Arg Gly720 725 730aaa tac atg acg gtc agt gaa ctg aaa acg gag gtg ttt ggc atc atg2377
Lys Tyr Met Thr Val Ser Glu Leu Lys Thr Glu Val Phe Gly Ile Met735 740 745cag gct ttt aac cgg cat atc ccg gcg gaa gag cag tta cgt cgc tac2425Gln Ala Phe Asn Arg His Ile Pro Ala Glu Glu Gln Leu Arg Arg Tyr750 755 760ggt gaa gtc cgt aac cag aat ggc agt gaa cag cag caa aaa cag gct2473Gly Glu Val Arg Asn Gln Asn Gly Ser Glu Gln Gln Gln Lys Gln Ala765 770 775gaa atg gcg cta aat cag tta att aac cgt tat cag atg ata cgt gca2521Glu Met Ala Leu Asn Gln Leu Ile Asn Arg Tyr Gln Met Ile Arg Ala780 785 790 795ggc aaa caa tagtggtagc cataatgcag gagcaaagcc tgaatcagga2570Gly Lys Glnagagttattc tgactgagtt tggttttctg gcgattcttg tg atg gtg gga tgt 2624Met Val Gly Cys800gct tgg tta gct gaa cag gcc ttt tcc gac cat gcg ctt tca cca cac2672Ala Trp Leu Ala Glu Gln Ala Phe Ser Asp His Ala Leu Ser Pro His805 810 815agt gct tgg ccg tac agt gca tcg cgc gat gcc ggg ctg gcc gat acg2720Ser Ala Trp Pro Tyr Ser Ala Ser Arg Asp Ala Gly Leu Ala Asp Thr820 825 830ggc gcg ggc ggc tat ccc act tgt aaa cag cgg tgg gcc gac gac acc2768Gly Ala Gly Gly Tyr Pro Thr Cys Lys Gln Arg Trp Ala Asp Asp Thr835 840 845 850gtt ggg ctg aaa gcc cgt cta ctg caa ctt cct gcc cta gat atc tgg2816Val Gly Leu Lys Ala Arg Leu Leu Gln Leu Pro Ala Leu Asp Ile Trp855 860 865acg gcg ttt aaa aaa atc gac cag tcg cag gta gtg tat gaa gag gcc2864Thr Ala Phe Lys Lys Ile Asp Gln Ser Gln Val Val Tyr Glu Glu Ala870 875 880gtg ctg cgc tcg cgg gtc agt gaa cga aat atg cag gta tcg cag aat2912Val Leu Arg Ser Arg Val Ser Glu Arg Asn Met Gln Val Ser Gln Asn885 890 895ggg cgc gtt tat cca agc tat ggc ggt aac gtt gat ggc acc gtc gcc2960Gly Arg Val Tyr Pro Ser Tyr Gly Gly Asn Val Asp Gly Thr Val Ala
900 905 910aat gcc gcc acc cgg ttg gca tcc ggc gct aga aat atc ctc ggc agc3008Asn Ala Ala Thr Arg Leu Ala Ser Gly Ala Arg Asn Ile Leu Gly Ser915 920 925 930ata gcg gca tgt acg gca ttc gac agc gtg cgt taggcactac cg atg gta 3059Ile Ala Ala Cys Thr Ala Phe Asp Ser Val Arg Met Val935 940cag gcg cag ctg caa ata gcg ctg gtg atc tgt att ccg ctg ata acg3107Gln Ala Gln Leu Gln Ile Ala Leu Val Ile Cys Ile Pro Leu Ile Thr945 950 955ctc tgt tcg gcg tgg gat gtg aaa gta gtg atg acg ctg acg ttt gtg3155Leu Cys Ser Ala Trp Asp Val Lys Val Val Met Thr Leu Thr Phe Val960 965 970 975cag ttt gca cta ttt ttc ctc acc ttt tgg tgg gaa ctg gca cgg tgg3203Gln Phe Ala Leu Phe Phe Leu Thr Phe Trp Trp Glu Leu Ala Arg Trp980 985 990ctt gat agc tgg ctg ctg gat gtg ctc tac aac agc gat acc cac agt3251Leu Asp Ser Trp Leu Leu Asp Val Leu Tyr Asn Ser Asp Thr His Ser99510001005agc tgg aat tta gcc ggg atc cag aat acg cag gat gac gtg att atc3299Ser Trp Asn Leu Ala Gly Ile Gln Asn Thr Gln Asp Asp Val Ile Ile101010151020aat ctg gtg atg agg ttg atg ttt ctg gtg ttg ccg aca ttc tgg ctg3347Asn Leu Val Met Arg Leu Met Phe Leu Val Leu Pro Thr Phe Trp Leu102510301035ggg gcg atg acg tgg gct gga gtg agg gtt ggc gtg gcg ctg aat gga3395Gly Ala Met Thr Trp Ala Gly Val Arg Val Gly Val Ala Leu Asn Gly1040 104510501055gcg ctg gcg gga tgattgggag gtgattcgcc aatctcactt tcctatacac3447Ala Leu Ala Glyatataaaatg ta atg aaa tat ctc ttt ttt gag aat ata cat tct ata ttt 3498Met Lys Tyr Leu Phe Phe Glu Asn Ile His Ser Ile Phe106010651070tta aca ttc agt ctc ttc cga aca tct gtg tcg cct gat ttc cca atg3546Leu Thr Phe Ser Leu Phe Arg Thr Ser Val Ser Pro Asp Phe Pro Met107510801085
att ttt gca ttg ccc tca atc att tta ggt caa ttt acg acc aac caa3594Ile Phe Ala Leu Pro Ser Ile Ile Leu Gly Gln Phe Thr Thr Asn Gln109010951100tta act aac ttt gtg ata tgt atg ggt aac acc gtt gaa cgt cgg ctg3642Leu Thr Asn Phe Val Ile Cys Met Gly Asn Thr Val Glu Arg Arg Leu1105 111011151120ggt gtt gtt cat aat ccc ttt aaa agg tct ggg gat ggc cat gac ctc3690Gly Val Val His Asn Pro Phe Lys Arg Ser Gly Asp Gly His Asp Leu112511301135agg gcg gta gcg tgaccaaagt tcatatccat accaattatt tttatttaaa3742Arg Ala Val Ala1140atatcaactt attcgagttg ttttatttag ttcaaagaag gtatcaaa ttg ata gtt 3799Leu Ile Valata gat ttt ttt tgt ggc tgt ggt gga gcc agt gaa ggg cta cgt cag3847Ile Asp Phe Phe Cys Gly Cys Gly Gly Ala Ser Glu Gly Leu Arg Gln114511501155gct ggc ttt gat atc gag ctt gga tta gat att gac caa caa gca tca3895Ala Gly Phe Asp Ile Glu Leu Gly Leu Asp Ile Asp Gln Gln Ala Ser1160 116511701175gaa aca ttt aaa gct aat ttc cct gat gca aaa ttc atc caa gat gat3943Glu Thr Phe Lys Ala Asn Phe Pro Asp Ala Lys Phe Ile Gln Asp Asp118011851190att agg aaa atc gaa cct caa gat atc tcc gac atc att gat att aaa3991Ile Arg Lys Ile Glu Pro Gln Asp Ile Ser Asp Ile Ile Asp Ile Lys119512001205gct aaa cgg cct ttg tta ctg agt gca tgt gca cca tgt caa cca ttt4039Ala Lys Arg Pro Leu Leu Leu Ser Ala Cys Ala Pro Cys Gln Pro Phe121012151220tcg caa cag aat aaa aat aaa act agt gac gac tca agg aga aat cta4087Ser Gln Gln Asn Lys Asn Lys Thr Ser Asp Asp Ser Arg Arg Asn Leu122512301235cta aat gaa act cat cgt ttt att aga gaa ctt ctt cct gaa tat att4135Leu Asn Glu Thr His Arg Phe Ile Arg Glu Leu Leu Pro Glu Tyr Ile1240 124512501255
atg ctt gaa aat gtt cct gga atg caa aaa att gat gaa gaa aaa gaa4183Met Leu Glu Asn Val Pro Gly Met Gln Lys Ile Asp Glu Glu Lys Glu126012651270ggc cca ttt cag gag ttt att aag cta ctt aaa gag tta gag tat aac4231Gly Pro Phe Gln Glu Phe Ile Lys Leu Leu Lys Glu Leu Glu Tyr Asn127512801285tat ata tct ttt ata gcc aat gct gag aac tat ggg att ccc caa aga4279Tyr Ile Ser Phe Ile Ala Asn Ala Glu Asn Tyr Gly Ile Pro Gln Arg129012951300aga aaa aga ctc gtg ctc tta gct agt cga gta ggt aaa gtt acc cta4327Arg Lys Arg Leu Val Leu Leu Ala Ser Arg Val Gly Lys Val Thr Leu130513101315cca gag ata acc cat ggt aaa aat aaa atc cca ttc aaa act gta cga4375Pro Glu Ile Thr His Gly Lys Asn Lys Ile Pro Phe Lys Thr Val Arg1320 132513301335gat tat atc cag gac ttc aca aag tta tgt tca gga gaa acc gac ccc4423Asp Tyr Ile Gln Asp Phe Thr Lys Leu Cys Ser Gly Glu Thr Asp Pro134013451350aaa gat cct tta cat agg gct gga aca ctg agc cct ctt aac cta aaa4471Lys Asp Pro Leu His Arg Ala Gly Thr Leu Ser Pro Leu Asn Leu Lys135513601365aga att atg cac act cca gaa gga ggg gat aga aga aat tgg cca gaa4519Arg Ile Met His Thr Pro Glu Gly Gly Asp Arg Arg Asn Trp Pro Glu137013751380gag tta gtt aat aaa tgc cat aaa aat tat gat ggc cac aca gat act4567Glu Leu Val Asn Lys Cys His Lys Asn Tyr Asp Gly His Thr Asp Thr138513901395tat gga aga atg agt tgg gat aag cct gcg cct aca ctt acg acg aaa4615Tyr Gly Arg Met Ser Trp Asp Lys Pro Ala Pro Thr Leu Thr Thr Lys1400 140514101415tgt aat agt tac tcc aat ggt cgt ttt ggg cat cct gac ccc act caa4663Cys Asn Ser Tyr Ser Asn Gly Arg Phe Gly His Pro Asp Pro Thr Gln142014251430cat aga gca att agc ata aga gaa gca tca aga tta caa aca ttt cct4711His Arg Ala Ile Ser Ile Arg Glu Ala Ser Arg Leu Gln Thr Phe Pro143514401445
tta agc tat gtt ttt aaa ggt tcg ctg aat tca atg gca aag caa atc4759Leu Ser Tyr Val Phe Lys Gly Ser Leu Asn Ser Met Ala Lys Gln Ile145014551460ggc aat gct gta cct tgc gaa ctc gct aga cta ttt ggg cta cat ctc4807Gly Asn Ala Val Pro Cys Glu Leu Ala Arg Leu Phe Gly Leu His Leu146514701475ata gaa aat tgt act aat aag gat tca tagatatatg gctaaaataa 4854Ile Glu Asn Cys Thr Asn Lys Asp Ser1480 1485gaacaaaggc tcgagctttg gac atg ctt ggc aga caa caa att gca ggt ata 4907Met Leu Gly Arg Gln Gln Ile Ala Gly Ile14901495cct act gcc ttg agt gag tta ttt aaa aat gct cat gat gcc tat gct4955Pro Thr Ala Leu Ser Glu Leu Phe Lys Asn Ala His Asp Ala Tyr Ala150015051510gat aat gtc gaa gtt gat ttt ttt agg aaa gaa aat ctt ctt atc ttg5003Asp Asn Val Glu Val Asp Phe Phe Arg Lys Glu Asn Leu Leu Ile Leu1515 152015251530aga gat gat gga tta ggt atg aca acc gat gaa ttt gaa gag agg tgg5051Arg Asp Asp Gly Leu Gly Met Thr Thr Asp Glu Phe Glu Glu Arg Trp153515401545ttg act att gga acc tcc agc aaa tta atc gac gat gat gca att aat5099Leu Thr Ile Gly Thr Ser Ser Lys Leu Ile Asp Asp Asp Ala Ile Asn155015551560aaa cca gca gtg gat agt aat aaa gcc ttt cgc cct atc atg gga gag5147Lys Pro Ala Val Asp Ser Asn Lys Ala Phe Arg Pro Ile Met Gly Glu156515701575aaa gga ata ggc cgt tta tct atc gca gca att gga cca cag gtg ctg5195Lys Gly Ile Gly Arg Leu Ser Ile Ala Ala Ile Gly Pro Gln Val Leu158015851590gtt ctt act agg gcc aaa aga gac aat gag ctt aag cca tta gtt gct5243Val Leu Thr Arg Ala Lys Arg Asp Asn Glu Leu Lys Pro Leu Val Ala1595 160016051610gca ttt gtt aat tgg agt tta ttt gct ata cca tca ctt gat ctt gat5291Ala Phe Val Asn Trp Ser Leu Phe Ala Ile Pro Ser Leu Asp Leu Asp161516201625
gat ata gaa ata cca att aga act att atc aac gac gaa tgc ttc act5339Asp Ile Glu Ile Pro Ile Arg Thr Ile Ile Asn Asp Glu Cys Phe Thr163016351640aaa aaa act ctt gat gag atg att gag caa gca aga aat aat tta gac5387Lys Lys Thr Leu Asp Glu Met Ile Glu Gln Ala Arg Asn Asn Leu Asp164516501655tct tta tca cac aaa ata tca aaa tca aaa gta tca caa ata aat aca5435Ser Leu Ser His Lys Ile Ser Lys Ser Lys Val Ser Gln Ile Asn Thr166016651670caa tta tca tct ttt gaa ttt gat cct att cta tgg gaa aaa aaa tta5483Gln Leu Ser Ser Phe Glu Phe Asp Pro Ile Leu Trp Glu Lys Lys Leu1675 168016851690ggt ggg cta aga cta tct gga gat ggg cat gga act cac ttc ata ata5531Gly Gly Leu Arg Leu Ser Gly Asp Gly His Gly Thr His Phe Ile Ile169517001705atg cct acc gaa gaa ata tta ata gat gac att tcc acg agc gat agc5579Met Pro Thr Glu Glu Ile Leu Ile Asp Asp Ile Ser Thr Ser Asp Ser171017151720aat aaa aca tca gag cag tct tct cgc tta gaa aaa gct tta tta ggt5627Asn Lys Thr Ser Glu Gln Ser Ser Arg Leu Glu Lys Ala Leu Leu Gly172517301735ttt aca aac aca atg tac agt gat tca aac cct cct att ata gct cgt5675Phe Thr Asn Thr Met Tyr Ser Asp Ser Asn Pro Pro Ile Ile Ala Arg174017451750ttt aga gac tat ctg gaa gat ggt gag tgc att gac aga att agc gaa5723Phe Arg Asp Tyr Leu Glu Asp Gly Glu Cys Ile Asp Arg Ile Ser Glu1755 176017651770tca att ttt ttt aca ccg caa gaa ttc aat ctt gca gat cac cac att5771Ser Ile Phe Phe Thr Pro Gln Glu Phe Asn Leu Ala Asp His His Ile177517801785gaa gga tgg ttc aat gaa ttt ggt caa ttc agt gga act gtt tct gtt5819Glu Gly Trp Phe Asn Glu Phe Gly Gln Phe Ser Gly Thr Val Ser Val179017951800tat ggt gaa gag cca att cat cat gtc gtg act tgg aaa aat aat aat5867Tyr Gly Glu Glu Pro Ile His His Val Val Thr Trp Lys Asn Asn Asn180518101815
caa tta acc caa tgc ggt cca ttt aaa ata aaa tta gcg tat att cat5915Gln Leu Thr Gln Cys Gly Pro Phe Lys Ile Lys Leu Ala Tyr Ile His182018251830ggt cgg ctt cgt gat tca cgc tta ccc atg gag ttg tgg gcc cot ctg5963Gly Arg Leu Arg Asp Ser Arg Leu Pro Met Glu Leu Trp Ala Pro Leu1835 184018451850aag gag aaa aca gat aga tat ggt ggt tta tat atc tat cga gat gga6011Lys Glu Lys Thr Asp Arg Tyr Gly Gly Leu Tyr Ile Tyr Arg Asp Gly185518601865tta aga att ttg ccc tat gga gat tca gat acg gat ttt cta aaa ata6059Leu Arg Ile Leu Pro Tyr Gly Asp Ser Asp Thr Asp Phe Leu Lys Ile187018751880gaa aag aga aga acg tta tcc gct tct gaa tat ttt ttc tca tat cga6107Glu Lys Arg Arg Thr Leu Ser Ala Ser Glu Tyr Phe Phe Ser Tyr Arg188518901895cgt ttg ttt gga gca ata gaa tta aca aaa gaa aac aat gct tca tta6155Arg Leu Phe Gly Ala Ile Glu Leu Thr Lys Glu Asn Asn Ala Ser Leu190019051910gtt gaa aaa gct ggg cga gaa gga ttc att gaa aat aag cca tat aaa6203Val Glu Lys Ala Gly Arg Glu Gly Phe Ile Glu Asn Lys Pro Tyr Lys1915 192019251930cag ttt aaa gaa atg ctt gaa aat ttc ttc atc gaa atc gca aga gat6251Gln Phe Lys Glu Met Leu Glu Asn Phe Phe Ile Glu Ile Ala Arg Asp193519401945ttc ttt aag gac gat ggc gat atg tct gaa tta ttt gtt gag aca aag6299Phe Phe Lys Asp Asp Gly Asp Met Ser Glu Leu Phe Val Glu Thr Lys195019551960caa cgt aga aat gaa gaa cat gat ttg tta tct aaa aga tct aaa caa6347Gln Arg Arg Asn Glu Glu His Asp Leu Leu Ser Lys Arg Ser Lys Gln196519701975act aaa gct aaa aaa gat aga tta aag aaa gat ctg tat gat ttt ttt6395Thr Lys Ala Lys Lys Asp Arg Leu Lys Lys Asp Leu Tyr Asp Phe Phe198019851990gat aag tta gat aat gat tac tgg aat att gaa ata aat aag cta atc6443Asp Lys Leu Asp Asn Asp Tyr Trp Asn Ile Glu Ile Asn Lys Leu Ile1995 200020052010
aat aaa aac gag gaa tat ttc tcc agt aca gaa ata aca gac acc aat6491Asn Lys Asn Glu Glu Tyr Phe Ser Ser Thr Glu Ile Thr Asp Thr Asn201520202025ata gat tat gta tac aat aaa att aaa gaa caa aat gat gct atc att6539Ile Asp Tyr Val Tyr Asn Lys Ile Lys Glu Gln Asn Asp Ala Ile Ile203020352040aaa aat cta cgt aat tct gtg gat ata aag aaa ccc tct gga gtt gga6587Lys Asn Leu Arg Asn Ser Val Asp Ile Lys Lys Pro Ser Gly Val Gly204520502055tta aca aaa gag tta tct aat tta tgg gat aga tat caa ata gaa aga6635Leu Thr Lys Glu Leu Ser Asn Leu Trp Asp Arg Tyr Gln Ile Glu Arg206020652070caa aaa ata ctg tta tca cta aat gag cta aaa gat aac gtt gat aga6683Gln Lys Ile Leu Leu Ser Leu Asn Glu Leu Lys Asp Asn Val Asp Arg2075 208020852090aag ctt ata gaa ctg gat aat aaa aat aat gat ttt ctc aac tta cgg6731Lys Leu Ile Glu Leu Asp Asn Lys Asn Asn Asp Phe Leu Asn Leu Arg209521002105aag aga ctt gaa gat tct ttg aat cta caa caa agt tac tat gaa aaa6779Lys Arg Leu Glu Asp Ser Leu Asn Leu Gln Gln Ser Tyr Tyr Glu Lys211021152120gaa cta aca aag tta tat aat gac gct aaa aat gct ttg aaa gat gtg6827Glu Leu Thr Lys Leu Tyr Asn Asp Ala Lys Asn Ala Leu Lys Asp Val212521302135caa tct aaa gca aat agg tta att tct gat aat aag aaa aaa cat aag6875Gln Ser Lys Ala Asn Arg Leu Ile Ser Asp Asn Lys Lys Lys His Lys214021452150agt gaa cta aaa aac att tct tat gaa ttc caa tca act aat ctc aat6923Ser Glu Leu Lys Asn Ile Ser Tyr Glu Phe Gln Ser Thr Asn Leu Asn2155 216021652170ggc aaa gat act gcg tat ata ttg gat gta aaa aga aat cta gaa agt6971Gly Lys Asp Thr Ala Tyr Ile Leu Asp Val Lys Arg Asn Leu Glu Ser217521802185aaa att gag aat act tca aac gaa gtg att aat gaa ata aga aaa cta7019Lys Ile Glu Asn Thr Ser Asn Glu Val Ile Asn Glu Ile Arg Lys Leu219021952200
acc gac cag att gca ata att agt gat agt acc act tct gaa aat tta7067Thr Asp Gln Ile Ala Ile Ile Ser Asp Ser Thr Thr Ser Glu Asn Leu220522102215tca tcg gct caa gta act gaa gca atc gaa act gaa ctt gaa cat tta7115Ser Ser Ala Gln Val Thr Glu Ala Ile Glu Thr Glu Leu Glu His Leu222022252230cga gac caa caa gca aat aac gca gag tta ata cta ctt ggc atg gct7163Arg Asp Gln Gln Ala Asn Asn Ala Glu Leu Ile Leu Leu Gly Met Ala2235 224022452250ctt tct gta gta cat cat gaa ttt aat ggt aat att agg gca att aga7211Leu Ser Val Val His His Glu Phe Asn Gly Asn Ile Arg Ala Ile Arg225522602265agt gcg cta agg gaa tta aaa gca tgg gct gac aga aat cct aag ctt7259Ser Ala Leu Arg Glu Leu Lys Ala Trp Ala Asp Arg Asn Pro Lys Leu227022752280gat att ata tac caa aaa atc aga act agt ttt gat cac tta gat ggt7307Asp Ile Ile Tyr Gln Lys Ile Arg Thr Ser Phe Asp His Leu Asp Gly228522902295tat tta aaa acc ttt aca cca ttg aca aga cgt tta agt cgc tct aaa7355Tyr Leu Lys Thr Phe Thr Pro Leu Thr Arg Arg Leu Ser Arg Ser Lys230023052310acc aat ata act gga act gcc att tta gaa ttt atc aga gat gta ttc7403Thr Asn Ile Thr Gly Thr Ala Ile Leu Glu Phe Ile Arg Asp Val Phe2315 232023252330gat gat cgt ctt gag aaa gaa gga att gaa tta ttc act acc tca aag7451Asp Asp Arg Leu Glu Lys Glu Gly Ile Glu Leu Phe Thr Thr Ser Lys233523402345ttt gtt aat caa gaa att gta act tac aca tca acc att tac cct gtc7499Phe Val Asn Gln Glu Ile Val Thr Tyr Thr Ser Thr Ile Tyr Pro Val235023552360ttt ata aat cta att gat aac gca ata tac tgg ctt ggg aaa aca act7547Phe Ile Asn Leu Ile Asp Asn Ala Ile Tyr Trp Leu Gly Lys Thr Thr236523702375gga gaa aaa aga ctt ata ctt gat gct act gaa aca gga ttt gtt att7595Gly Glu Lys Arg Leu Ile Leu Asp Ala Thr Glu Thr Gly Phe Val Ile238023852390
ggt gat act ggt ccc ggt gtt tca act aga gat cga gat ata ata ttt7643Gly Asp Thr Gly Pro Gly Val Ser Thr Arg Asp Arg Asp Ile Ile Phe2395 240024052410gat atg gga ttt aca cga aaa aca gga ggg cgt gga atg gga tta ttc 7691Asp Met Gly Phe Thr Arg Lys Thr Gly Gly Arg Gly Met Gly Leu Phe241524202425att tcc aaa gag tgt tta tct cga gat gga ttt act ata aga ttg gat7739Ile Ser Lys Glu Cys Leu Ser Arg Asp Gly Phe Thr Ile Arg Leu Asp243024352440gat tac act cct gaa cag ggt gct ttc ttt att att gag cca tca gaa7787Asp Tyr Thr Pro Glu Gln Gly Ala Phe Phe Ile Ile Glu Pro Ser Glu244524502455gaa aca agt gaa tag cggatataaa taa atg aca agc tct act gat ttt 7836Glu Thr Ser GluMet Thr Ser Ser Thr Asp Phe2460 24652470cat aaa ctt tct gaa gac tgc gtt cgc cgt ttt tta cat tct gta gtt7884His Lys Leu Ser Glu Asp Cys Val Arg Arg Phe Leu His Ser Val Val247524802485gct gta gat gac aat atg tct ttt gga gct ggt agt gat act ttc cct7932Ala Val Asp Asp Asn Met Ser Phe Gly Ala Gly Ser Asp Thr Phe Pro249024952500aca gac gaa gat att aat gct tta gtt gat ccc gac gat gat cct aca7980Thr Asp Glu Asp Ile Asn Ala Leu Val Asp Pro Asp Asp Asp Pro Thr250525102515cca ata ata aca gca tca gca tcc cca agg ata gaa tca act aaa tca8028Pro Ile Ile Thr Ala Ser Ala Ser Pro Arg Ile Glu Ser Thr Lys Ser252025252530aaa gca aag gta aaa aac cat cct ttt gat tac caa gct cta gca gaa8076Lys Ala Lys Val Lys Asn His Pro Phe Asp Tyr Gln Ala Leu Ala Glu2535 254025452550gct ttc gcc aaa gat ggt att gct tgt tgc gga tta tta gct aag agt8124Ala Phe Ala Lys Asp Gly Ile Ala Cys Cys Gly Leu Leu Ala Lys Ser255525602565ttt aat gtt gaa gaa aga gat ata att aca gca tca tcc cac aag gca8172Phe Asn Val Glu Glu Arg Asp Ile Ile Thr Ala Ser Ser His Lys Ala257025752580
gat ata aca ata ctt gac tgg gat atg caa agc gat agt ggg caa ttt8220Asp Ile Thr Ile Leu Asp Trp Asp Met Gln Ser Asp Ser Gly Gln Phe258525902595gct att gaa ata ata aaa tcg ata atc gtt tca gat ata aat tct gga8268Ala Ile Glu Ile Ile Lys Ser Ile Ile Val Ser Asp Ile Asn Ser Gly260026052610gga cgt tta cgt ctt ctt tct att tat act ggt gaa cat gtt act gct8316Gly Arg Leu Arg Leu Leu Ser Ile Tyr Thr Gly Glu His Val Thr Ala2615 262026252630gtt ata act aag ttg aac aat gag tta aag aaa aca tac cgt agc gta8364Val Ile Thr Lys Leu Asn Asn Glu Leu Lys Lys Thr Tyr Arg Ser Val263526402645ata aaa aat gat gat agt att ttt att gaa gat aac tat gca ctc gaa8412Ile Lys Asn Asp Asp Ser Ile Phe Ile Glu Asp Asn Tyr Ala Leu Glu265026552660caa tgg tgt ata gtt gtt att agt aaa gac gtt tat gaa aaa gat ctt8460Gln Trp Cys Ile Val Val Ile Ser Lys Asp Val Tyr Glu Lys Asp Leu266526702675cca aat gtg tta ata aaa aaa ttc act aac ctt aca gct ggg ttg cta8508Pro Asn Val Leu Ile Lys Lys Phe Thr Asn Leu Thr Ala Gly Leu Leu268026852690tcc aac gcc gca ctc tct tgc att tct gaa ata aga gaa aaa acc cat8556Ser Asn Ala Ala Leu Ser Cys Ile Ser Glu Ile Arg Glu Lys Thr His2695 270027052710ggg ata tta aca aaa tat aat aat aaa tta gac act gca tat gtt tcc8604Gly Ile Leu Thr Lys Tyr Asn Asn Lys Leu Asp Thr Ala Tyr Val Ser271527202725cac atc tta aat tta ata aaa tcc aag gag tca agg gca tat gct tat8652His Ile Leu Asn Leu Ile Lys Ser Lys Glu Ser Arg Ala Tyr Ala Tyr273027352740gaa aat gct cat gat tat gca gta gat tta att tct gaa gaa ata aga8700Glu Asn Ala His Asp Tyr Ala Val Asp Leu Ile Ser Glu Glu Ile Arg274527502755tca ata ttg caa ata agt gaa aac tta aag aaa tct cta agc aaa aac8748Ser Ile Leu Gln Ile Ser Glu Asn Leu Lys Lys Ser Leu Ser Lys Asn276027652770
tcc tta tcc cat tgg cct att ttt cac tat gca aaa aat ggt tgt aag8796Ser Leu Ser His Trp Pro Ile Phe His Tyr Ala Lys Asn Gly Cys Lys2775 278027852790aat ttt cta tta act gga aaa aaa caa aaa gac tta tca gta gaa cat8844Asn Phe Leu Leu Thr Gly Lys Lys Gln Lys Asp Leu Ser Val Glu His279528002805cta agg aat ata ctc tct gct gat tct tta gaa gaa att caa cac gct8892Leu Arg Asn Ile Leu Ser Ala Asp Ser Leu Glu Glu Ile Gln His Ala281028152820att gaa cac gca tct tta ggt aaa aag gaa tac tta agc caa gat ggt8940Ile Glu His Ala Ser Leu Gly Lys Lys Glu Tyr Leu Ser Gln Asp Gly282528302835gaa gaa gat aaa aag tta atg caa tta tgc tct ctg gaa atc acg cgc8988Glu Glu Asp Lys Lys Leu Met Gln Leu Cys Ser Leu Glu Ile Thr Arg284028452850agg agt tta aga tat cat tct cat ata gat aat gtg tcc tta aaa caa9036Arg Ser Leu Arg Tyr His Ser His Ile Asp Asn Val Ser Leu Lys Gln2855 286028652870gga act tta ctt tta gat gca tat aat ttt gtc tat cta tgc ata caa9084Gly Thr Leu Leu Leu Asp Ala Tyr Asn Phe Val Tyr Leu Cys Ile Gln287528802885cca tta tgt gat agc gtc aga ttg cat gaa aaa gcc gat ttt tta ttc9132Pro Leu Cys Asp Ser Val Arg Leu His Glu Lys Ala Asp Phe Leu Phe289028952900ctc agg gga aca ctg gac gat aat aat tac aat ttg tta atc gaa gat9180Leu Arg Gly Thr Leu Asp Asp Asn Asn Tyr Asn Leu Leu Ile Glu Asp290529102915gaa tat ggc ggt ttt tat aaa att aaa atg ccg gca aaa gct tct aat9228Glu Tyr Gly Gly Phe Tyr Lys Ile Lys Met Pro Ala Lys Ala Ser Asn292029252930att att tca ttt tca ttt gga gtc gaa aat gga aac ggt gtc atc ata9276Ile Ile Ser Phe Ser Phe Gly Val Glu Asn Gly Asn Gly Val Ile Ile2935 294029452950ggg aaa aag aac aat cta gtt aat act gac tat atc tca ttc gtt cct9324Gly Lys Lys Asn Asn Leu Val Asn Thr Asp Tyr Ile Ser Phe Val Pro295529602965
tta ctc gtt gaa aaa ata tct act cca aaa gta ttg aaa tgg atc ggg9372Leu Leu Val Glu Lys Ile Ser Thr Pro Lys Val Leu Lys Trp Ile Gly297029752980gaa ata aaa aca acg tac gcg caa aaa ata aca act gat att gtt gct9420Glu Ile Lys Thr Thr Tyr Ala Gln Lys Ile Thr Thr Asp Ile Val Ala298529902995aat ctg tca aga ata ggt tta gat caa cat gag tgg tta cga ata aaa9468Asn Leu Ser Arg Ile Gly Leu Asp Gln His Glu Trp Leu Arg Ile Lys300030053010tca aaa gat ata taaatgatta tatatgccgt cgttttataa aaactggcgg9520Ser Lys Asp Ile3015catgtatatc tagttagtcc atcatagaag tcaagaaatt tagtttgccc tatatcttat 9580agaaaatata ttttatatgc ttaaaaaaca ccatctttct aagatggcat ttatgtgctt 9640tgtttcgatc aattacaact gatatattac catattgatt aattttatgt tatttaccaa 9700agtaacggca tcttaatata tcgtcataat atagtgcgcg ttctgactct aatactgaaa 9760aatttatttg ttctatttta cacttactgc aaatagcatc cagtttatca tatagtgtcg 9820catcaattgg cgcag atg tca tca cgc caa atc ctt gag cat tat aat gct 9871Met Ser Ser Arg Gln Ile Leu Glu His Tyr Asn Ala302030253030cta aca tat ccc cta cat caa tca atc ttg ttg cag ata atg act tcg9919Leu Thr Tyr Pro Leu His Gln Ser Ile Leu Leu Gln Ile Met Thr Ser303530403045aat ttg tta tca gtt tgc act gga aaa tcc att tac gag gat atc tcc9967Asn Leu Leu Ser Val Cys Thr Gly Lys Ser Ile Tyr Glu Asp Ile Ser305030553060ggc agt tct tgg aat atc ata cac ttc aat atc cct ctc ccc atc tct10015Gly Ser Ser Trp Asn Ile Ile His Phe Asn Ile Pro Leu Pro Ile Ser306530703075aga gcg aga ctt tcc ata ttt tct tat tgt gtc aga att aaa cct tgg10063Arg Ala Arg Leu Ser Ile Phe Ser Tyr Cys Val Arg Ile Lys Pro Trp308030853090atg agt atg gat tac atg taaccggctc atttaaaccg tctggtctgt 10111Met Ser Met Asp Tyr Met
30953100ttcctccggt tttacaaaaa ta atg tcc atc att ttt aat gga cac tat cgt 10163Met Ser Ile Ile Phe Asn Gly His Tyr Arg31053110atg aaa cac cgg act tgg atc act gaa gct tta cgt ctt cac ttt gaa10211Met Lys His Arg Thr Trp Ile Thr Glu Ala Leu Arg Leu His Phe Glu311531203125gaa cat tta ccc cag gtt gtg gtc ggg cgt cgc ctg ggc gta cca aaa10259Glu His Leu Pro Gln Val Val Val Gly Arg Arg Leu Gly Val Pro Lys313031353140tca aca gct tgt ggt atg ttc gtg cgc ttt cgc aaa gct ggc ttt tca10307Ser Thr Ala Cys Gly Met Phe Val Arg Phe Arg Lys Ala Gly Phe Ser314531503155tgg cct ctg ccc gca ggt atg tcg gag cgg gag ctt gat ggc cgt ctt10355Trp Pro Leu Pro Ala Gly Met Ser Glu Arg Glu Leu Asp Gly Arg Leu316031653170tac ggg agt acc tcc aca gta cct gtc gta ctt tgt agt gga tcg gta10403Tyr Gly Ser Thr Ser Thr Val Pro Val Val Leu Cys Ser Gly Ser Val3175 318031853190att cag gac acc tcg aaa tcc tgt taatgttaaa acagtgaaaa tgaggtgatg 10457Ile Gln Asp Thr Ser Lys Ser Cys3195c atg atc aaa act cgt cgg act aaa cgt acc ttt tcc ccg gag ttc aag 10506Met Ile Lys Thr Arg Arg Thr Lys Arg Thr Phe Ser Pro Glu Phe Lys320032053210ctt gaa gct ttc gag cag gtg gtg gtt aaa tac cag cgt gat gtc aga10554Leu Glu Ala Phe Glu Gln Val Val Val Lys Tyr Gln Arg Asp Val Arg3215 322032253230gaa gtc gcg cag gca ctc gag ctc aac cct gac cat ttg cgt aaa tgg10602Glu Val Ala Gln Ala Leu Glu Leu Asn Pro Asp His Leu Arg Lys Trp323532403245ata cgg ttg tat aag cag gaa ctt cag ggt att gag cca gct ggt aat10650Ile Arg Leu Tyr Lys Gln Glu Leu Gln Gly Ile Glu Pro Ala Gly Asn325032553260gct att acc cct gaa caa cgc gaa att cag cag ctt aaa gcg cag ata10698Ala Ile Thr Pro Glu Gln Arg Glu Ile Gln Gln Leu Lys Ala Gln Ile
326532703275aag cgc gtt gag atg gaa aaa gaa ata cta aag cag gct gcc gtg ctg10746Lys Arg Val Glu Met Glu Lys Glu Ile Leu Lys Gln Ala Ala Val Leu328032853290atg agc gaa atc ccc ggg aag ctg tcg cgc taatcacaca gctgaaagca 10796Met Ser Glu Ile Pro Gly Lys Leu Ser Arg3295 3300aagtggccag tgtgggttat ttgtcattta ttcggtatta accgtagcgt ttattacgcg 10856caggtgaagc gtcctgttaa tgtgcaaaga attgaattac gaagccgggt gagggctttc 10916catgctctca gtcgtggcgc agccgggtag ccgggcaatc agtcagatgt tgcgccagag 10976tggcgttgat gcaggccggt ggctggcatg acgactgatg cgggaatgag ggctgacaag 11036tcgacagccg gttaaacatc acaaccgggt aaacgaagac aaaagtccgc cattgccaaa 11096tttactgaac cggcaatttc accccgccgc accaaactgc gtctggtgcg gcgacatcag 11156ttttattcg 11165<210>35<211>366<212>PRT<213>大肠杆菌<400>35Ser Asp Met Gln Arg Gly Ile Gln Ala Ala Thr Ala Ala Leu Gln Gly1 5 10 15Leu Val Gly Gly Asn Met Ala Gly Ala Leu Ala Gly Ala Ser Ala Pro20 25 30Glu Leu Ala Asn Ile Ile Gly His His Ala Gly Ile Asp Asp Asn Thr35 40 45Ala Ala Lys Ala Ile Ala His Ala Ile Leu Gly Gly Val Thr Ala Ala50 55 60Leu Gln Gly Asn Ser Ala Ala Ala Gly Ala Ile Gly Ala Gly Thr Gly65 70 75 80Glu Val Ile Ala Ser Ala Ile Ala Lys Ser Leu Tyr Pro Gly Val Asp85 90 95
Pro Ser Lys Leu Thr Glu Asp Gln Lys Gln Thr Val Ser Thr Leu Ala100 105 110Thr Leu Ser Ala Gly Met Ala Gly Gly Ile Ala Ser Gly Asp Val Ala115 120 125Gly Ala Ala Ala Gly Ala Gly Ala Gly Lys Asn Val Val Glu Asn Asn130 135 140Ala Leu Ser Leu Val Ala Arg Gly Cys Ala Val Ala Ala Pro Cys Arg145 150 155 160Thr Lys Val Ala Glu Gln Leu Leu Glu Ile Gly Ala Lys Ala Gly Met165 170 175Ala Gly Leu Ala Gly Ala Ala Val Lys Asp Met Ala Asp Arg Met Thr180 185 190Ser Asp Glu Leu Glu His Leu Ile Thr Leu Gln Met Met Gly Asn Asp195 200 205Glu Ile Thr Thr Lys Tyr Leu Ser Ser Leu His Asp Lys Tyr Gly Ser210 215 220Gly Ala Ala Ser Asn Pro Asn Ile Gly Lys Asp Leu Thr Asp Ala Glu225 230 235 240Lys Val Glu Leu Gly Gly Ser Gly Ser Gly Thr Gly Thr Pro Pro Pro245 250 255Ser Glu Asn Asp Pro Lys Gln Gln Asn Glu Lys Thr Val Asp Lys Leu260 265 270Asn Gln Lys Gln Glu Ser Ala Ile Lys Lys Ile Asp Asn Thr Ile Lys275 280 285Asn Ala Leu Lys Asp His Asp Ile Ile Gly Thr Leu Lys Asp Met Asp290 295 300Gly Lys Pro Val Pro Lys Glu Asn Gly Gly Tyr Trp Asp His Met Gln305 310 315 320Glu Met Gln Asn Thr Leu Arg Gly Leu Arg Asn His Ala Asp Thr Leu325 330 335Lys Asn Val Asn Asn Pro Glu Ala Gln Ala Ala Tyr Gly Arg Ala Thr340 345 350
Asp Ala Ile Asn Lys Ile Glu Ser Ala Leu Lys Gly Tyr Gly355 360 365<210>36<211>128<212>PRT<213>大肠杆菌<400>36Met Ile Thr Leu Arg Lys Leu Ile Gly Asn Ile Asn Met Thr Lys Glu1 5 10 15Pro Glu Gln Gln Ser Pro Leu Glu Leu Trp Phe Glu Arg Ile Ile Asp20 25 30Val Pro Leu Glu Lys Leu Thr Val Glu Asp Leu Cys Arg Ala Ile Arg35 40 45Gln Asn Leu Cys Ile Asp Gln Leu Met Pro Arg Val Leu Glu Val Leu50 55 60Thr Lys Glu Pro Leu Ala Gly Glu Tyr Tyr Asp Gly Glu Leu Ile Ala65 70 75 80Ala Leu Ser Thr lle Lys Gly Glu Asp Leu Lys Asp Gln Lys Ser Thr85 90 95Phe Thr Gln Ile Arg Gln Leu Ile Asn Gln Leu Glu Pro Ser Asp Ile100 105 110Asn Asp Asp Leu Arg Lys Asp Ile Leu Lys Ile Asn Gln Ile Ile Val115 120 125<210>37<211>107<212>PRT<213>大肠杆菌<400>37Met Val Ala Lys Ala Phe Ala Tyr Ala Leu Asn Gln Trp Pro Ala Leu1 5 10 15Thr Tyr Tyr Ala Asn Asp Gly Trp Val Glu Ile Asp Asn Asn Ile Ala20 25 30
Glu Asn Ala Leu Arg Ala Val Ser Leu Gly Arg Lys Asn Phe Leu Phe35 40 45Phe Gly Ser Asp His Gly Gly Glu Arg Gly Ala Leu Leu Tyr Ser Leu50 55 60Ile Gly Thr Cys Lys Leu Asn Asp Val Asp Pro Glu Ser Tyr Leu Arg65 70 75 80His Val Leu Ala Val Ile Ala Asp Trp Pro Val Asn Arg Val Ser Glu85 90 95Leu Leu Pro Trp Arg Ile Ala Leu Pro Ala Glu100 105<210>38<211>86<212>PRT<213>大肠杆菌<400>38Met Leu Met Ser Val Gln Lys Glu Lys Asn Val Ala Glu Ser Val Val1 5 10 15Ser Glu Thr His Thr Gly Asp Ser Val Tyr Ala Ser Leu Phe Glu Lys20 25 30Ile Asn Leu Asn Pro Val Ser Ala Leu Ser Ala Leu Asp Asn Pro Phe35 40 45Arg Ser Ala Asp Asn Ala Thr Gly Arg Ile Thr Ser Ser Ile Gln Pro50 55 60Ala Val Gln cys Ala Ala Ala Ala Ala Thr Glu Gly Ser Cys Pro Arg65 70 75 80Gln Ser Pro Cys Ser Gly85<210>39<211>111<212>PRT<213>大肠杆菌<400>39Met Val Asp Asn Trp Gln Lys Ser Val Arg Ser Arg Ala Leu Pro Glu
1 5 10 15Glu Ala Met Thr Gly Trp Asn Glu Gly Met Ile Arg Leu Gln Gln Leu20 25 30Ala Glu Arg Leu Asn Arg Gln Asp Glu Gln Arg Gly Lys Tyr Met Thr35 40 45Val Ser Glu Leu Lys Thr Glu Val Phe Gly Ile Met Gln Ala Phe Asn50 55 60Arg His Ile Pro Ala Glu Glu Gln Leu Arg Arg Tyr Gly Glu Val Arg65 70 75 80Asn Gln Asn Gly Ser Glu Gln Gln Gln Lys Gln Ala Glu Met Ala Leu85 90 95Asn Gln Leu Ile Asn Arg Tyr Gln Met Ile Arg Ala Gly Lys Gln100 105 110<210>40<211>143<212>PRT<213>大肠杆菌<400>40Met Val Gly Cys Ala Trp Leu Ala Glu Gln Ala Phe Ser Asp His Ala1 5 10 15Leu Ser Pro His Ser Ala Trp Pro Tyr Ser Ala Ser Arg Asp Ala Gly20 25 30Leu Ala Asp Thr Gly Ala Gly Gly Tyr Pro Thr Cys Lys Gln Arg Trp35 40 45Ala Asp Asp Thr Val Gly Leu Lys Ala Arg Leu Leu Gln Leu Pro Ala50 55 60Leu Asp Ile Trp Thr Ala Phe Lys Lys Ile Asp Gln Ser Gln Val Val65 70 75 80Tyr Glu Glu Ala Val Leu Arg Ser Arg Val Ser Glu Arg Asn Met Gln85 90 95Val Ser Gln Asn Gly Arg Val Tyr Pro Ser Tyr Gly Gly Asn Val Asp100 105 110
Gly Thr Val Ala Asn Ala Ala Thr Arg Leu Ala Ser Gly Ala Arg Asn115 120 125Ile Leu Gly Ser Ile Ala Ala Cys Thr Ala Phe Asp Ser Val Arg130 135 140<210>41<211>118<212>PRT<213>大肠杆菌<400>41Met Val Gln Ala Gln Leu Gln Ile Ala Leu Val Ile Cys Ile Pro Leu1 5 10 15Ile Thr Leu Cys Ser Ala Trp Asp Val Lys Val Val Met Thr Leu Thr20 25 30Phe Val Gln Phe Ala Leu Phe Phe Leu Thr Phe Trp Trp Glu Leu Ala35 40 45Arg Trp Leu Asp Ser Trp Leu Leu Asp Val Leu Tyr Asn Ser Asp Thr50 55 60His Ser Ser Trp Asn Leu Ala Gly Ile Gln Asn Thr Gln Asp Asp Val65 70 75 80Ile Ile Asn Leu Val Met Arg Leu Met Phe Leu Val Leu Pro Thr Phe85 90 95Trp Leu Gly Ala Met Thr Trp Ala Gly Val Arg Val Gly Val Ala Leu100 105 110Asn Gly Ala Leu Ala Gly115<210>42<211>81<212>PRT<213>大肠杆菌<400>42Met Lys Tyr Leu Phe Phe Glu Asn Ile His Ser Ile Phe Leu Thr Phe1 5 10 15Ser Leu Phe Arg Thr Ser Val Ser Pro Asp Phe Pro Met Ile Phe Ala
20 25 30Leu Pro Ser Ile Ile Leu Gly Gln Phe Thr Thr Asn Gln Leu Thr Asn35 40 45Phe Val Ile Cys Met Gly Asn Thr Val Glu Arg Arg Leu Gly Val Val50 55 60His Asn Pro Phe Lys Arg Ser Gly Asp Gly His Asp Leu Arg Ala Val65 70 75 80Ala<210>43<211>348<212>PRT<213>大肠杆菌<400>43Leu Ile Val Ile Asp Phe Phe Cys Gly Cys Gly Gly Ala Ser Glu Gly1 5 10 15Leu Arg Gln Ala Gly Phe Asp Ile Glu Leu Gly Leu Asp Ile Asp Gln20 25 30Gln Ala Ser Glu Thr Phe Lys Ala Asn Phe Pro Asp Ala Lys Phe Ile35 40 45Gln Asp Asp Ile Arg Lys Ile Glu Pro Gln Asp Ile Ser Asp Ile Ile50 55 60Asp Ile Lys Ala Lys Arg Pro Leu Leu Leu Ser Ala Cys Ala Pro Cys65 70 75 80Gln Pro Phe Ser Gln Gln Asn Lys Asn Lys Thr Ser Asp Asp Ser Arg85 90 95Arg Asn Leu Leu Asn Glu Thr His Arg Phe Ile Arg Glu Leu Leu Pro100 105 110Glu Tyr Ile Met Leu Glu Asn Val Pro Gly Met Gln Lys Ile Asp Glu115 120 125Glu Lys Glu Gly Pro Phe Gln Glu Phe Ile Lys Leu Leu Lys Glu Leu130 135 140Glu Tyr Asn Tyr Ile Ser Phe Ile Ala Asn Ala Glu Asn Tyr Gly Ile
145 150 155 160Pro Gln Arg Arg Lys Arg Leu Val Leu Leu Ala Ser Arg Val Gly Lys165 170 175Val Thr Leu Pro Glu Ile Thr His Gly Lys Asn Lys Ile Pro Phe Lys180 185 190Thr Val Arg Asp Tyr Ile Gln Asp Phe Thr Lys Leu Cys Ser Gly Glu195 200 205Thr Asp Pro Lys Asp Pro Leu His Arg Ala Gly Thr Leu Ser Pro Leu210 215 220Asn Leu Lys Arg Ile Met His Thr Pro Glu Gly Gly Asp Arg Arg Asn225 230 235 240Trp Pro Glu Glu Leu Val Asn Lys Cys His Lys Asn Tyr Asp Gly His245 250 255Thr Asp Thr Tyr Gly Arg Met Ser Trp Asp Lys Pro Ala Pro Thr Leu260 265 270Thr Thr Lys Cys Asn Ser Tyr Ser Asn Gly Arg Phe Gly His Pro Asp275 280 285Pro Thr Gln His Arg Ala Ile Ser Ile Arg Glu Ala Ser Arg Leu Gln290 295 300Thr Phe Pro Leu Ser Tyr Val Phe Lys Gly Ser Leu Asn Ser Met Ala305 310 315 320Lys Gln Ile Gly Asn Ala Val Pro Cys Glu Leu Ala Arg Leu Phe Gly325 330 335Leu His Leu Ile Glu Asn Cys Thr Asn Lys Asp Ser340 345<210>44<211>974<212>PRT<213>大肠杆菌<400>44Met Leu Gly Arg Gln Gln Ile Ala Gly Ile Pro Thr Ala Leu Ser Glu1 5 10 15
Leu Phe Lys Asn Ala His Asp Ala Tyr Ala Asp Asn Val Glu Val Asp20 25 30Phe Phe Arg Lys Glu Asn Leu Leu Ile Leu Arg Asp Asp Gly Leu Gly35 40 45Met Thr Thr Asp Glu Phe Glu Glu Arg Trp Leu Thr Ile Gly Thr Ser50 55 60Ser Lys Leu Ile Asp Asp Asp Ala Ile Asn Lys Pro Ala Val Asp Ser65 70 75 80Asn Lys Ala Phe Arg Pro Ile Met Gly Glu Lys Gly Ile Gly Arg Leu85 90 95Ser Ile Ala Ala Ile Gly Pro Gln Val Leu Val Leu Thr Arg Ala Lys100 105 110Arg Asp Asn Glu Leu Lys Pro Leu Val Ala Ala Phe Val Asn Trp Ser115 120 125Leu Phe Ala Ile Pro Ser Leu Asp Leu Asp Asp Ile Glu Ile Pro Ile130 135 140Arg Thr Ile Ile Asn Asp Glu Cys Phe Thr Lys Lys Thr Leu Asp Glu145 150 155 160Met Ile Glu Gln Ala Arg Asn Asn Leu Asp Ser Leu Ser His Lys Ile165 170 175Ser Lys Ser Lys Val Ser Gln Ile Asn Thr Gln Leu Ser Ser Phe Glu180 185 190Phe Asp Pro Ile Leu Trp Glu Lys Lys Leu Gly Gly Leu Arg Leu Ser195 200 205Gly Asp Gly His Gly Thr His Phe Ile Ile Met Pro Thr Glu Glu Ile210 215 220Leu Ile Asp Asp Ile Ser Thr Ser Asp Ser Asn Lys Thr Ser Glu Gln225 230 235 240Ser Ser Arg Leu Glu Lys Ala Leu Leu Gly Phe Thr Asn Thr Met Tyr245 250 255Ser Asp Ser Asn Pro Pro Ile Ile Ala Arg Phe Arg Asp Tyr Leu Glu260 265 270
Asp Gly Glu Cys Ile Asp Arg Ile Ser Glu Ser Ile Phe Phe Thr Pro275 280 285Gln Glu Phe Asn Leu Ala Asp His His Ile Glu Gly Trp Phe Asn Glu290 295 300Phe Gly Gln Phe Ser Gly Thr Val Ser Val Tyr Gly Glu Glu Pro Ile305 310 315 320His His Val Val Thr Trp Lys Asn Asn Asn Gln Leu Thr Gln Cys Gly325 330 335Pro Phe Lys Ile Lys Leu Ala Tyr Ile His Gly Arg Leu Arg Asp Ser340 345 350Arg Leu Pro Met Glu Leu Trp Ala Pro Leu Lys Glu Lys Thr Asp Arg355 360 365Tyr Gly Gly Leu Tyr Ile Tyr Arg Asp Gly Leu Arg Ile Leu Pro Tyr370 375 380Gly Asp Ser Asp Thr Asp Phe Leu Lys Ile Glu Lys Arg Arg Thr Leu385 390 395 400Ser Ala Ser Glu Tyr Phe Phe Ser Tyr Arg Arg Leu Phe Gly Ala Ile405 410 415Glu Leu Thr Lys Glu Asn Asn Ala Ser Leu Val Glu Lys Ala Gly Arg420 425 430Glu Gly Phe Ile Glu Asn Lys Pro Tyr Lys Gln Phe Lys Glu Met Leu435 440 445Glu Asn Phe Phe Ile Glu Ile Ala Arg Asp Phe Phe Lys Asp Asp Gly450 455 460Asp Met Ser Glu Leu Phe Val Glu Thr Lys Gln Arg Arg Asn Glu Glu465 470 475 480His Asp Leu Leu Ser Lys Arg Ser Lys Gln Thr Lys Ala Lys Lys Asp485 490 495Arg Leu Lys Lys Asp Leu Tyr Asp Phe Phe Asp Lys Leu Asp Asn Asp500 505 510Tyr Trp Asn Ile Glu Ile Asn Lys Leu Ile Asn Lys Asn Glu Glu Tyr515 520 525
Phe Ser Ser Thr Glu Ile Thr Asp Thr Asn Ile Asp Tyr Val Tyr Asn530 535 540Lys Ile Lys Glu Gln Asn Asp Ala Ile Ile Lys Asn Leu Arg Asn Ser545 550 555 560Val Asp Ile Lys Lys Pro Ser Gly Val Gly Leu Thr Lys Glu Leu Ser565 570 575Asn Leu Trp Asp Arg Tyr Gln Ile Glu Arg Gln Lys Ile Leu Leu Ser580 585 590Leu Asn Glu Leu Lys Asp Asn Val Asp Arg Lys Leu Ile Glu Leu Asp595 600 605Asn Lys Asn Asn Asp Phe Leu Asn Leu Arg Lys Arg Leu Glu Asp Ser610 615 620Leu Asn Leu Gln Gln Ser Tyr Tyr Glu Lys Glu Leu Thr Lys Leu Tyr625 630 635 640Asn Asp Ala Lys Asn Ala Leu Lys Asp Val Gln Ser Lys Ala Asn Arg645 650 655Leu Ile Ser Asp Asn Lys Lys Lys His Lys Ser Glu Leu Lys Asn Ile660 665 670Ser Tyr Glu Phe Gln Ser Thr Asn Leu Asn Gly Lys Asp Thr Ala Tyr675 680 685Ile Leu Asp Val Lys Arg Asn Leu Glu Ser Lys Ile Glu Asn Thr Ser690 695 700Asn Glu Val Ile Asn Glu Ile Arg Lys Leu Thr Asp Gln Ile Ala Ile705 710 715 720Ile Ser Asp Ser Thr Thr Ser Glu Asn Leu Ser Ser Ala Gln Val Thr725 730 735Glu Ala Ile Glu Thr Glu Leu Glu His Leu Arg Asp Gln Gln Ala Asn740 745 750Asn Ala Glu Leu Ile Leu Leu Gly Met Ala Leu Ser Val Val His His755 760 765Glu Phe Asn Gly Asn Ile Arg Ala Ile Arg Ser Ala Leu Arg Glu Leu770 775 780
Lys Ala Trp Ala Asp Arg Asn Pro Lys Leu Asp Ile Ile Tyr Gln Lys785 790 795 800Ile Arg Thr Ser Phe Asp His Leu Asp Gly Tyr Leu Lys Thr Phe Thr805 810 815Pro Leu Thr Arg Arg Leu Ser Arg Ser Lys Thr Asn Ile Thr Gly Thr820 825 830Ala Ile Leu Glu Phe Ile Arg Asp Val Phe Asp Asp Arg Leu Glu Lys835 840 845Glu Gly Ile Glu Leu Phe Thr Thr Ser Lys Phe Val Asn Gln Glu Ile850 855 860Val Thr Tyr Thr Ser Thr Ile Tyr Pro Val Phe Ile Asn Leu Ile Asp865 870 875 880Asn Ala Ile Tyr Trp Leu Gly Lys Thr Thr Gly Glu Lys Arg Leu Ile885 890 895Leu Asp Ala Thr Glu Thr Gly Phe Val Ile Gly Asp Thr Gly Pro Gly900 905 910Val Ser Thr Arg Asp Arg Asp Ile Ile Phe Asp Met Gly Phe Thr Arg915 920 925Lys Thr Gly Gly Arg Gly Met Gly Leu Phe Ile Ser Lys Glu Cys Leu930 935 940Ser Arg Asp Gly Phe Thr Ile Arg Leu Asp Asp Tyr Thr Pro Glu Gln945 950 955 960Gly Ala Phe Phe Ile Ile Glu Pro Ser Glu Glu Thr Ser Glu965 970<210>45<211>555<212>PRT<213>大肠杆菌<400>45Met Thr Ser Ser Thr Asp Phe His Lys Leu Ser Glu Asp Cys Val Arg1 5 10 15Arg Phe Leu His Ser Val Val Ala Val Asp Asp Asn Met Ser Phe Gly20 25 30
Ala Gly Ser Asp Thr Phe Pro Thr Asp Glu Asp Ile Asn Ala Leu Val35 40 45Asp Pro Asp Asp Asp Pro Thr Pro Ile Ile Thr Ala Ser Ala Ser Pro50 55 60Arg Ile Glu Ser Thr Lys Ser Lys Ala Lys Val Lys Asn His Pro Phe65 70 75 80Asp Tyr Gln Ala Leu Ala Glu Ala Phe Ala Lys Asp Gly Ile Ala Cys85 90 95Cys Gly Leu Leu Ala Lys Ser Phe Asn Val Glu Glu Arg Asp Ile Ile100 105 110Thr Ala Ser Ser His Lys Ala Asp Ile Thr Ile Leu Asp Trp Asp Met115 120 125Gln Ser Asp Ser Gly Gln Phe Ala Ile Glu Ile Ile Lys Ser Ile Ile130 135 140Val Ser Asp Ile Asn Ser Gly Gly Arg Leu Arg Leu Leu Ser Ile Tyr145 150 155 160Thr Gly Glu His Val Thr Ala Val Ile Thr Lys Leu Asn Asn Glu Leu165 170 175Lys Lys Thr Tyr Arg Ser Val Ile Lys Asn Asp Asp Ser Ile Phe Ile180 185 190Glu Asp Asn Tyr Ala Leu Glu Gln Trp Cys Ile Val Val Ile Ser Lys195 200 205Asp Val Tyr Glu Lys Asp Leu Pro Asn Val Leu Ile Lys Lys Phe Thr210 215 220Asn Leu Thr Ala Gly Leu Leu Ser Asn Ala Ala Leu Ser Cys Ile Ser225 230 235 240Glu Ile Arg Glu Lys Thr His Gly Ile Leu Thr Lys Tyr Asn Asn Lys245 250 255Leu Asp Thr Ala Tyr Val Ser His Ile Leu Asn Leu Ile Lys Ser Lys260 265 270Glu Ser Arg Ala Tyr Ala Tyr Glu Asn Ala His Asp Tyr Ala Val Asp275 280 285
Leu Ile Ser Glu Glu Ile Arg Ser Ile Leu Gln Ile Ser Glu Asn Leu290 295 300Lys Lys Ser Leu Ser Lys Asn Ser Leu Ser His Trp Pro Ile Phe His305 310 315 320Tyr Ala Lys Asn Gly Cys Lys Asn Phe Leu Leu Thr Gly Lys Lys Gln325 330 335Lys Asp Leu Ser Val Glu His Leu Arg Asn Ile Leu Ser Ala Asp Ser340 345 350Leu Glu Glu Ile Gln His Ala Ile Glu His Ala Ser Leu Gly Lys Lys355 360 365Glu Tyr Leu Ser Gln Asp Gly Glu Glu Asp Lys Lys Leu Met Gln Leu370 375 380Cys Ser Leu Glu Ile Thr Arg Arg Ser Leu Arg Tyr His Ser His Ile385 390 395 400Asp Asn Val Ser Leu Lys Gln Gly Thr Leu Leu Leu Asp Ala Tyr Asn405 410 415Phe Val Tyr Leu Cys Ile Gln Pro Leu Cys Asp Ser Val Arg Leu His420 425 430Glu Lys Ala Asp Phe Leu Phe Leu Arg Gly Thr Leu Asp Asp Asn Asn435 440 445Tyr Asn Leu Leu Ile Glu Asp Glu Tyr Gly Gly Phe Tyr Lys Ile Lys450 455 460Met Pro Ala Lys Ala Ser Asn Ile Ile Ser Phe Ser Phe Gly Val Glu465 470 475 480Asn Gly Asn Gly Val Ile Ile Gly Lys Lys Asn Asn Leu Val Asn Thr485 490 495Asp Tyr Ile Ser Phe Val Pro Leu Leu Val Glu Lys Ile Ser Thr Pro500 505 510Lys Val Leu Lys Trp Ile Gly Glu Ile Lys Thr Thr Tyr Ala Gln Lys515 520 525Ile Thr Thr Asp Ile Val Ala Asn Leu Ser Arg Ile Gly Leu Asp Gln530 535 540
His Glu Trp Leu Arg Ile Lys Ser Lys Asp Ile545 550 555<210>46<211>82<212>PRT<213>大肠杆菌<400>46Met Ser Ser Arg Gln Ile Leu Glu His Tyr Asn Ala Leu Thr Tyr Pro1 5 10 15Leu His Gln Ser Ile Leu Leu Gln Ile Met Thr Ser Asn Leu Leu Ser20 25 30Val Cys Thr Gly Lys Ser Ile Tyr Glu Asp Ile Ser Gly Ser Ser Trp35 40 45Asn Ile Ile His Phe Asn Ile Pro Leu Pro Ile Ser Arg Ala Arg Leu50 55 60Ser Ile Phe Ser Tyr Cys Val Arg Ile Lys Pro Trp Met Ser Met Asp65 70 75 80Tyr Met<210>47<211>98<212>PRT<213>大肠杆菌<400>47Met Ser Ile Ile Phe Asn Gly His Tyr Arg Met Lys His Arg Thr Trp1 5 10 15Ile Thr Glu Ala Leu Arg Leu His Phe Glu Glu His Leu Pro Gln Val20 25 30Val Val Gly Arg Arg Leu Gly Val Pro Lys Ser Thr Ala Cys Gly Met35 40 45Phe Val Arg Phe Arg Lys Ala Gly Phe Ser Trp Pro Leu Pro Ala Gly50 55 60Met Ser Glu Arg Glu Leu Asp Gly Arg Leu Tyr Gly Ser Thr Ser Thr
65 70 75 80Val Pro Val Val Leu Cys Ser Gly Ser Val Ile Gln Asp Thr Ser Lys85 90 95Ser Cys<210>48<211>106<212>PRT<213>大肠杆菌<400>48Met Ile Lys Thr Arg Arg Thr Lys Arg Thr Phe Ser Pro Glu Phe Lys1 5 10 15Leu Glu Ala Phe Glu Gln Val Val Val Lys Tyr Gln Arg Asp Val Arg20 25 30Glu Val Ala Gln Ala Leu Glu Leu Asn Pro Asp His Leu Arg Lys Trp35 40 45Ile Arg Leu Tyr Lys Gln Glu Leu Gln Gly Ile Glu Pro Ala Gly Asn50 55 60Ala Ile Thr Pro Glu Gln Arg Glu Ile Gln Gln Leu Lys Ala Gln Ile65 70 75 80Lys Arg Val Glu Met Glu Lys Glu Ile Leu Lys Gln Ala Ala Val Leu85 90 95Met Ser Glu Ile Pro Gly Lys Leu Ser Arg100 105<210>49<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>49tgctctagag ccattactca gaatggg 27
<210>50<211>26<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>50cgcgagctcg acgactgaat gatccc 26<210>51<211>26<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>51tcccccgggt actgcagcac tcaacc 26<210>52<211>26<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>52gatcccggga ccactgaaat gcgtgc 26<210>53<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>53tcgtctagag atgatggtga tggagcg 27
<210>54<211>28<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>54gaactgcagc caaatactga taccaccc 28<210>55<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>55gaactgcagg ctaaaacaga agacgcg 27<210>56<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>56catgcatgca ctccatatga caaccgc 27<210>57<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>57tcgtctagaa tgaagctgcg catgagg 27
<210>58<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>58caactgcagt cgcaaattgc gaactgg 27<210>59<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>59caactgcaga ccgcaacttt tcgacgc 27<210>60<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>60catgcatgcc agtgagccat tgttccc 27<210>61<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>61tgctctagat acgactctga caggagg 27
<210>62<211>26<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>62tcagatatca actaccagca gtttgg 26<210>63<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>63tcagatatcc ataaagagtg acgtggc 27<210>64<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>64tgctctagaa aacgtggcaa cagagcg 27<210>65<211>26<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>65tgctctagaa ggcgttgtcg atcctg 26
<210>66<211>28<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>66gaactgcagg aaaaggccga gcagactg 28<210>67<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>67gaactgcagt acagccatgt ttacggt 27<210>68<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>68catgcatgcg gtgtacgaca gtttgcg 27<210>69<211>26<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>69tgctctagac acatcatggg cacacc 26
<210>70<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>70gaactgcaga accgtccaca tcaggcg 27<210>71<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>71gaactgcaga ccctgcttgc cattccg 27<210>72<211>27<212>DNA<213>人工序列<220>
<223>人工序列描述寡核苷酸<400>72catgcatgca taagcgtcga acaggcg 2权利要求
1.一种用于治疗用途的由操纵子编码的肽、或其在革兰氏阴性菌中在氨基酸或核苷酸水平上至少具有30％同源性的同源物或其功能片段，其中所述的操纵子包括可获自大肠杆菌K1的本文鉴定为creC、recG、yggN、eck1、iroD、iroC、iroE、mtd2和ms1-16在内的任意基因。
2.一种根据权利要求1所述的肽，它包括本文鉴定为SEQ ID NOS.5、7、9、23、24、25、26、28、29、31、32和35-48的任意氨基酸序列。
3.一种用于治疗用途的编码权利要求1或权利要求2的肽的多核苷酸。
4.一种用于表达权利要求1或权利要求2的肽的转化的宿主。
5.一种包括权利要求1或权利要求2的肽的疫苗，或用于其表达的工具。
6.一种包括带有毒力基因突变的微生物的疫苗，其中所述的基因编码权利要求1或权利要求2的肽。
7.一种根据权利要求6所述的疫苗，其中所述的基因位于致病性岛内，其中所述的岛包括本文鉴定的基因。
8.权利要求1-4中任意一项所述的产物或SEQ ID NO.33在筛选有潜能的药物或在检测毒性中的用途。
9.权利要求1-4中任意一项所述的产物在制备用于治疗或预防与革兰氏阴性菌导致的感染有关的疾病的药物中的用途。
10.根据权利要求9所述的用途，其中所述的细菌是大肠杆菌。
全文摘要
本发明以鉴定一系列大肠杆菌K1中的毒力基因为基础，其产物可能与生物体的致病性有关。对该基因的鉴定使得可以将它们或其表达的产物以许多方式用于治疗感染。
文档编号C12N15/11GK1891713SQ20061009172
公开日2007年1月10日 申请日期1999年11月9日 优先权日1998年11月9日
发明者H·R·克鲁克, E·E·克拉克, P·H·艾沃莱斯特, G·杜甘, D·W·霍尔登, J·E·施艾, R·G·菲尔德曼 申请人:微科学有限公司