CN112930395A - 靶向rna的融合蛋白组合物和使用方法 - Google Patents

靶向rna的融合蛋白组合物和使用方法 Download PDF

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CN112930395A
CN112930395A CN201980050249.4A CN201980050249A CN112930395A CN 112930395 A CN112930395 A CN 112930395A CN 201980050249 A CN201980050249 A CN 201980050249A CN 112930395 A CN112930395 A CN 112930395A
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D·A·内尔斯
R·巴特拉
E·杨
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Rocana Biological Co ltd
Locana Inc
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Abstract

公开了组合物，其包含：(a)包含特异性结合RNA分子内的靶序列的指导RNA(gRNA)的序列；以及(b)编码融合蛋白的序列，所述序列包含编码第一RNA结合多肽的序列和编码第二RNA结合多肽的序列，其中所述第一RNA结合多肽和所述第二RNA结合多肽都不包含显著DNA‑核酸酶活性，其中所述第一RNA结合多肽与所述第二RNA结合多肽不相同，并且其中所述第二RNA结合多肽包含RNA‑核酸酶活性。还提供了本公开文本的组合物的制备方法和使用方法。例如，本公开文本的组合物可以用于治疗受试者的疾病或障碍。本公开文本的示例性疾病或障碍包括遗传和表观遗传疾病或障碍。

Description

靶向RNA的融合蛋白组合物和使用方法
技术领域
本公开文本涉及分子生物学，并且更具体而言涉及用于修饰RNA分子的表达和活性的组合物和方法。
相关申请的交叉引用
本申请要求2018年6月8日提交的美国专利申请号62/682,271的优先权，将其内容通过引用以其整体并入本文。将2018年6月8日提交的美国专利申请号62/682,276的内容通过引用以其整体并入本文。
序列表的并入
将2019年6月6日创建的大小为773KB的名为“LOCN_002_001WO_SeqList_ST25”的文本文件的内容通过引用以其整体特此并入。
背景技术
对于特异性结合靶RNA分子以修饰所述RNA分子或由所述RNA分子编码的蛋白质的表达或活性的方法，在本领域中存在长期但未满足的需求。本公开文本提供了用于以序列特异性方式特异性靶向RNA分子的组合物和方法，所述序列特异性方式进一步排除DNA序列的修饰。
发明内容
本公开文本提供了一种组合物，其包含(a)包含特异性结合RNA分子内的靶序列的指导RNA(gRNA)的序列；以及(b)编码融合蛋白的序列，所述序列包含编码第一RNA结合多肽的序列和编码第二RNA结合多肽的序列，其中所述第一RNA结合多肽和所述第二RNA结合多肽都不包含显著DNA-核酸酶活性，其中所述第一RNA结合多肽与所述第二RNA结合多肽不相同，并且其中所述第二RNA结合多肽包含RNA-核酸酶活性，其中所述第一RNA结合多肽与所述第二RNA结合多肽不相同，并且其中所述第二RNA结合多肽包含RNA-核酸酶活性。
本公开文本还提供了一种组合物，所述组合物包含编码RNA指导的靶RNA结合融合蛋白的序列，所述序列包含(a)编码第一RNA结合多肽或其部分的序列；以及(b)编码第二RNA结合多肽的序列，其中所述第一RNA结合多肽结合由gRNA序列指导的靶RNA，并且其中所述第二RNA结合多肽包含RNA-核酸酶活性。
本公开文本另外提供了一种组合物，所述组合物包含编码靶RNA结合融合蛋白的序列，所述序列包含(a)编码第一RNA结合多肽或其部分的序列；以及(b)编码第二RNA结合多肽的序列，其中所述第一RNA结合多肽在没有gRNA序列的情况下结合靶RNA，并且其中所述第二RNA结合多肽包含RNA-核酸酶活性。
在本公开文本的组合物的一些实施方案中，所述靶序列包含至少一个重复的序列。
在本公开文本的组合物的一些实施方案中，包含所述gRNA的序列还包含编码能够在真核细胞中表达所述gRNA的启动子的序列。
在本公开文本的组合物的一些实施方案中，所述真核细胞是动物细胞。在一些实施方案中，所述动物细胞是哺乳动物细胞。在一些实施方案中，所述动物细胞是人细胞。
在本公开文本的组合物的一些实施方案中，所述启动子是组成型活性启动子。在一些实施方案中，所述启动子序列是从能够驱动RNA聚合酶的表达的启动子分离或衍生的。在一些实施方案中，所述启动子序列是从U6启动子分离或衍生的。在一些实施方案中，所述启动子是从能够驱动转移RNA(tRNA)的表达的启动子分离或衍生的序列。在一些实施方案中，所述启动子是从以下启动子分离或衍生的：丙氨酸tRNA启动子、精氨酸tRNA启动子、天冬酰胺tRNA启动子、天冬氨酸tRNA启动子、半胱氨酸tRNA启动子、谷氨酰胺tRNA启动子、谷氨酸tRNA启动子、甘氨酸tRNA启动子、组氨酸tRNA启动子、异亮氨酸tRNA启动子、亮氨酸tRNA启动子、赖氨酸tRNA启动子、甲硫氨酸tRNA启动子、苯丙氨酸tRNA启动子、脯氨酸tRNA启动子、丝氨酸tRNA启动子、苏氨酸tRNA启动子、色氨酸tRNA启动子、酪氨酸tRNA启动子或缬氨酸tRNA启动子。在一些实施方案中，所述启动子是从缬氨酸tRNA启动子分离或衍生的。
在本公开文本的组合物的一些实施方案中，包含所述gRNA的序列还包含与所述靶RNA序列特异性结合的间隔子序列。在一些实施方案中，所述间隔子序列与所述靶RNA序列具有至少50％、55％、60％、65％、70％、75％、80％、87％、90％、95％、97％、99％或之间的任何百分比的互补性。在一些实施方案中，所述间隔子序列与所述靶RNA序列具有100％互补性。在一些实施方案中，所述间隔子序列包含20个核苷酸或由其组成。在一些实施方案中，所述间隔子序列包含21个核苷酸或由其组成。在一些实施方案中，所述间隔子序列包含以下序列或由其组成：UGGAGCGAGCAUCCCCCAAA(SEQ ID NO:1)、GUUUGGGGGAUGCUCGCUCCA(SEQID NO:2)、CCCUCACUGCUGGGGAGUCC(SEQ ID NO:3)、GGACUCCCCAGCAGUGAGGG(SEQ ID NO:4)、GCAACUGGAUCAAUUUGCUG(SEQ ID NO:5)、GCAGCAAAUUGAUCCAGUUGC(SEQ ID NO:6)、GCAUUCUUAUCUGGUCAGUGC(SEQ ID NO:7)、GCACUGACCAGAUAAGAAUG(SEQ ID NO:8)、GAGCAGCAGCAGCAGCAGCAG(SEQ ID NO:9)、GCAGGCAGGCAGGCAGGCAGG(SEQ ID NO:10)、GCCCCGGCCCCGGCCCCGGC(SEQ ID NO:11)、或GCTGCTGCTGCTGCTGCTGC(SEQ ID NO:12)、GGGGCCGGGGCCGGGGCCGG(SEQ ID NO:74)、GGGCCGGGGCCGGGGCCGGG(SEQ ID NO:75)、GGCCGGGGCCGGGGCCGGGG(SEQ ID NO:76)、GCCGGGGCCGGGGCCGGGGC(SEQ ID NO:77)、CCGGGGCCGGGGCCGGGGCC(SEQ ID NO:78)或CGGGGCCGGGGCCGGGGCCG(SEQ ID NO:79)。
在本公开文本的组合物的一些实施方案中，包含所述gRNA的序列还包含与所述靶RNA序列特异性结合的间隔子序列。在一些实施方案中，所述间隔子序列与所述靶RNA序列具有至少50％、55％、60％、65％、70％、75％、80％、87％、90％、95％、97％、99％或之间的任何百分比的互补性。
在一些实施方案中，所述间隔子序列与所述靶RNA序列具有100％互补性。在一些实施方案中，所述间隔子序列包含20个核苷酸或由其组成。在一些实施方案中，所述间隔子序列包含21个核苷酸或由其组成。在一些实施方案中，所述间隔子序列包含以下序列或由其组成：GUGAUAAGUGGAAUGCCAUG(SEQ ID NO:14)、CUGGUGAACUUCCGAUAGUG(SEQ ID NO:15)或GAGATATAGCCTGGTGGTTC(SEQ ID NO:16)。
在本公开文本的组合物的一些实施方案中，包含所述gRNA的序列还包含与所述靶RNA序列特异性结合的间隔子序列。在一些实施方案中，所述间隔子序列与所述靶RNA序列具有至少50％、55％、60％、65％、70％、75％、80％、87％、90％、95％、97％、99％或之间的任何百分比的互补性。在一些实施方案中，所述间隔子序列与所述靶RNA序列具有100％互补性。在一些实施方案中，所述间隔子序列包含20个核苷酸或由其组成。在一些实施方案中，所述间隔子序列包含21个核苷酸或由其组成。在一些实施方案中，所述间隔子序列包含以下序列或由以下序列组成，所述序列包含序列CUG(SEQ ID NO:18)、CCUG(SEQ ID NO:19)、CAG(SEQ ID NO:80)、GGGGCC(SEQ ID NO:81)或其任何组合的至少1、2、3、4、5、6或7个重复。
在本公开文本的组合物的一些实施方案中，包含所述gRNA的序列还包含与所述第一RNA结合蛋白特异性结合的支架序列。在一些实施方案中，所述支架序列包含茎环结构。在一些实施方案中，所述支架序列包含90个核苷酸或由其组成。在一些实施方案中，所述支架序列包含93个核苷酸或由其组成。在一些实施方案中，所述支架序列包含以下序列或由其组成：GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUUU(SEQ ID NO:13)。在一些实施方案中，所述支架序列包含以下序列或由其组成：GGACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUU(SEQ ID NO:17)。在一些实施方案中，所述支架序列包含以下序列或由其组成：GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUUU(SEQ ID NO:82)或GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUUU(SEQ ID NO:83)。
在本公开文本的组合物的一些实施方案中，所述gRNA不结合或不选择性结合所述RNA分子内的第二序列。
在本公开文本的组合物的一些实施方案中，RNA基因组或RNA转录组包含所述RNA分子。
在本公开文本的组合物的一些实施方案中，所述第一RNA结合蛋白包含CRISPR-Cas蛋白。在一些实施方案中，所述CRISPR-Cas蛋白是II型CRISPR-Cas蛋白。在一些实施方案中，所述第一RNA结合蛋白包含Cas9多肽或其RNA结合部分。在一些实施方案中，所述CRISPR-Cas蛋白包含天然RNA核酸酶活性。在一些实施方案中，所述天然RNA核酸酶活性被降低或抑制。在一些实施方案中，所述天然RNA核酸酶活性被增加或诱导。在一些实施方案中，所述CRISPR-Cas蛋白包含天然DNA核酸酶活性并且所述天然DNA核酸酶活性被抑制。在一些实施方案中，所述CRISPR-Cas蛋白包含突变。在一些实施方案中，所述CRISPR-Cas蛋白的核酸酶结构域包含所述突变。在一些实施方案中，所述突变发生在编码所述CRISPR-Cas蛋白的核酸中。在一些实施方案中，所述突变发生在编码所述CRISPR-Cas蛋白的氨基酸中。在一些实施方案中，所述突变包含取代、插入、缺失、移码、倒位或转座。在一些实施方案中，所述突变包含核酸酶结构域、所述核酸酶结构域内的结合位点、所述核酸酶结构域内的活性位点或所述核酸酶结构域内的至少一个必需氨基酸残基的缺失。
在本公开文本的组合物的一些实施方案中，所述第一RNA结合蛋白包含CRISPR-Cas蛋白。在一些实施方案中，所述CRISPR-Cas蛋白是V型CRISPR-Cas蛋白。在一些实施方案中，所述第一RNA结合蛋白包含Cpf1多肽或其RNA结合部分。在一些实施方案中，所述CRISPR-Cas蛋白包含天然RNA核酸酶活性。在一些实施方案中，所述天然RNA核酸酶活性被降低或抑制。在一些实施方案中，所述天然RNA核酸酶活性被增加或诱导。在一些实施方案中，所述CRISPR-Cas蛋白包含天然DNA核酸酶活性并且所述天然DNA核酸酶活性被抑制。在一些实施方案中，所述CRISPR-Cas蛋白包含突变。在一些实施方案中，所述CRISPR-Cas蛋白的核酸酶结构域包含所述突变。在一些实施方案中，所述突变发生在编码所述CRISPR-Cas蛋白的核酸中。在一些实施方案中，所述突变发生在编码所述CRISPR-Cas蛋白的氨基酸中。在一些实施方案中，所述突变包含取代、插入、缺失、移码、倒位或转座。在一些实施方案中，所述突变包含核酸酶结构域、所述核酸酶结构域内的结合位点、所述核酸酶结构域内的活性位点或所述核酸酶结构域内的至少一个必需氨基酸残基的缺失。
在本公开文本的组合物的一些实施方案中，所述第一RNA结合蛋白包含CRISPR-Cas蛋白。在一些实施方案中，所述CRISPR-Cas蛋白是VI型CRISPR-Cas蛋白。在一些实施方案中，所述第一RNA结合蛋白包含Cas13多肽或其RNA结合部分。在一些实施方案中，所述第一RNA结合蛋白包含CasRx/Cas13d多肽或其RNA结合部分。在一些实施方案中，所述CRISPR-Cas蛋白包含天然RNA核酸酶活性。在一些实施方案中，所述天然RNA核酸酶活性被降低或抑制。在一些实施方案中，所述天然RNA核酸酶活性被增加或诱导。在一些实施方案中，所述CRISPR-Cas蛋白包含天然DNA核酸酶活性并且所述天然DNA核酸酶活性被抑制。在一些实施方案中，所述CRISPR-Cas蛋白包含突变。在一些实施方案中，所述CRISPR-Cas蛋白的核酸酶结构域包含所述突变。在一些实施方案中，所述突变发生在编码所述CRISPR-Cas蛋白的核酸中。在一些实施方案中，所述突变发生在编码所述CRISPR-Cas蛋白的氨基酸中。在一些实施方案中，所述突变包含取代、插入、缺失、移码、倒位或转座。在一些实施方案中，所述突变包含核酸酶结构域、所述核酸酶结构域内的结合位点、所述核酸酶结构域内的活性位点或所述核酸酶结构域内的至少一个必需氨基酸残基的缺失。
在本公开文本的组合物的一些实施方案中，所述第一RNA结合蛋白包含Pumilio和FBF(PUF)蛋白或其RNA结合部分。在一些实施方案中，所述第一RNA结合蛋白包含基于Pumilio的联合体(Pumilio-based assembly，PUMBY)蛋白或其RNA结合部分。
在本公开文本的组合物的一些实施方案中，所述第一RNA结合蛋白不需要多聚化以用于RNA结合活性。在一些实施方案中，所述第一RNA结合蛋白不是多聚体复合物的单体。在一些实施方案中，多聚体蛋白复合物不包含所述第一RNA结合蛋白。
在本公开文本的组合物的一些实施方案中，所述第一RNA结合蛋白与所述RNA分子内的靶序列选择性结合。在一些实施方案中，所述第一RNA结合蛋白不包含对所述RNA分子内的第二序列的亲和力。在一些实施方案中，所述第一RNA结合蛋白不包含对所述RNA分子内的第二序列的高亲和力或不选择性结合所述第二序列。
在本公开文本的组合物的一些实施方案中，RNA基因组或RNA转录组包含所述RNA分子。
在本公开文本的组合物的一些实施方案中，所述第一RNA结合蛋白包含在2个与1300个之间的氨基酸，包括端点。
在本公开文本的组合物的一些实施方案中，编码所述第一RNA结合蛋白的序列还包含编码核定位信号(NLS)、核输出信号(NES)或标签的序列。在一些实施方案中，编码核定位信号(NLS)的所述序列定位于编码所述第一RNA结合蛋白的序列的3'。在一些实施方案中，所述第一RNA结合蛋白包含在所述蛋白质的C末端的NLS。
在本公开文本的组合物的一些实施方案中，编码所述第一RNA结合蛋白的序列还包含编码第一NLS的第一序列和编码第二NLS的第二序列。在一些实施方案中，编码所述第一NLS或所述第二NLS的序列定位于编码所述第一RNA结合蛋白的序列的3'。在一些实施方案中，所述第一RNA结合蛋白包含在所述蛋白质的C末端的所述第一NLS或所述第二NLS。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含核酸酶结构域或由其组成。在一些实施方案中，所述第二RNA结合蛋白以与RNA缔合的方式结合RNA。在一些实施方案中，所述第二RNA结合蛋白以切割RNA的方式与RNA缔合。
在本公开文本的组合物的一些实施方案中，编码所述第二RNA结合蛋白的序列包含RNA酶或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶1或由其组成。在一些实施方案中，所述RNA酶1包含SEQ ID NO:20或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶4或由其组成。在一些实施方案中，所述RNA酶4包含SEQ ID NO:21或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶6或由其组成。在一些实施方案中，所述RNA酶6包含SEQ ID NO:22或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶7或由其组成。在一些实施方案中，所述RNA酶7包含SEQ ID NO:23或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶8或由其组成。在一些实施方案中，所述RNA酶8蛋白包含SEQ ID NO:24或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶2或由其组成。在一些实施方案中，所述RNA酶2蛋白包含SEQ ID NO:25或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶6PL或由其组成。在一些实施方案中，所述RNA酶6PL蛋白包含SEQ ID NO:26或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶L或由其组成。在一些实施方案中，所述RNA酶L蛋白包含SEQ ID NO:27或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶T2或由其组成。在一些实施方案中，所述RNA酶T2蛋白包含SEQ ID NO:28或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶11或由其组成。在一些实施方案中，所述RNA酶11蛋白包含SEQ ID NO:29或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含RNA酶T2样蛋白或由其组成。在一些实施方案中，所述RNA酶T2样蛋白包含SEQ ID NO:30或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(K41R))多肽或由其组成。在一些实施方案中，所述RNA酶1(K41R)多肽包含SEQ ID NO:116或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(K41R、D121E))多肽或由其组成。在一些实施方案中，所述RNA酶1(RNA酶1(K41R、D121E))多肽包含SEQ ID NO:66或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(K41R、D121E、H119N))多肽或由其组成。在一些实施方案中，所述RNA酶1(RNA酶1(K41R、D121E、H119N))多肽包含SEQ ID NO:118或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(H119N))多肽或由其组成。在一些实施方案中，所述RNA酶1(RNA酶1(H119N))多肽包含SEQ ID NO:119或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽或由其组成。在一些实施方案中，所述RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽包含SEQ IDNO:120或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽或由其组成。在一些实施方案中，所述RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N、K41R、D121E))多肽包含SEQ ID NO:121或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽或由其组成。在一些实施方案中，所述RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D))多肽包含SEQ ID NO:122或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含NOB1多肽或由其组成。在一些实施方案中，所述NOB1多肽包含SEQ ID NO:31或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶V(ENDOV)或由其组成。在一些实施方案中，所述ENDOV蛋白包含SEQ ID NO:32或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶G(ENDOG)或由其组成。在一些实施方案中，所述ENDOG蛋白包含SEQ ID NO:33或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶D1(ENDOD1)或由其组成。在一些实施方案中，所述ENDOD1蛋白包含SEQ ID NO:34或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含人瓣状内切核酸酶-1(hFEN1)或由其组成。在一些实施方案中，所述hFEN1蛋白包含SEQ ID NO:35或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含DNA修复内切核酸酶XPF(ERCC4)多肽或由其组成。在一些实施方案中，所述ERCC4蛋白包含SEQ ID NO:64或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶III样蛋白1(NTHL)多肽或由其组成。在一些实施方案中，所述NTHL多肽包含SEQ ID NO:123或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含人斯库拉芬蛋白(Schlafen)14(hSLFN14)多肽或由其组成。在一些实施方案中，所述hSLFN14多肽包含SEQ ID NO:36或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含人β-内酰胺酶样蛋白2(hLACTB2)多肽或由其组成。在一些实施方案中，所述hLACTB2多肽包含SEQ IDNO:37或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含无嘌呤/无嘧啶(AP)内切脱氧核糖核酸酶(APEX)多肽或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含无嘌呤/无嘧啶(AP)内切脱氧核糖核酸酶(APEX2)多肽或由其组成。在一些实施方案中，所述APEX2多肽包含SEQ ID NO:38或由其组成。在一些实施方案中，所述APEX2多肽包含SEQ ID NO:39或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含无嘌呤或无嘧啶位点裂解酶(APEX1)多肽或由其组成。在一些实施方案中，所述APEX1多肽包含SEQ IDNO:125或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含血管生成素(ANG)多肽或由其组成。在一些实施方案中，所述ANG多肽包含SEQ ID NO:40或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含热反应蛋白12(HRSP12)多肽或由其组成。在一些实施方案中，所述HRSP12多肽包含SEQ ID NO:41或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含含锌指CCCH型12A(Zinc Finger CCCH-Type Containing 12A，ZC3H12A)多肽或由其组成。在一些实施方案中，所述ZC3H12A多肽包含SEQ ID NO:42或由其组成。在一些实施方案中，所述ZC3H12A多肽包含SEQ ID NO:43或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含反应性中间亚胺脱氨酶A(Reactive Intermediate Imine Deaminase A，RIDA)多肽或由其组成。在一些实施方案中，所述RIDA多肽包含SEQ ID NO:44或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含磷脂酶D家族成员6(PDL6)多肽或由其组成。在一些实施方案中，所述PDL6多肽包含SEQ ID NO:126或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含线粒体核糖核酸酶P催化亚基(KIAA0391)多肽或由其组成。在一些实施方案中，所述KIAA0391多肽包含SEQ ID NO:127或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含阿尔古蛋白(argonaute)2(AGO2)多肽或由其组成。
在本公开文本的组合物的一些实施方案中，所述AGO2多肽包含SEQ ID NO:128或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含线粒体核酸酶EXOG(EXOG)多肽或由其组成。在一些实施方案中，所述EXOG多肽包含SEQ ID NO:129或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含含锌指CCCH型12D(ZC3H12D)多肽或由其组成。在一些实施方案中，所述ZC3H12D多肽包含SEQ IDNO:130或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含内质网核信号转导蛋白2(ERN2)多肽或由其组成。在一些实施方案中，所述ERN2多肽包含SEQ ID NO:131或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含回力球mRNA监督和核糖体挽救因子(pelota mRNA surveillance and ribosome rescue factor，PELO)多肽或由其组成。在一些实施方案中，所述PELO多肽包含SEQ ID NO:132或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含YBEY金属肽酶(YBEY)多肽或由其组成。在一些实施方案中，所述YBEY多肽包含SEQ ID NO:133或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含剪切和多聚腺苷酸化特异性因子4样蛋白(CPSF4L)多肽或由其组成。在一些实施方案中，所述CPSF4L多肽包含SEQ ID NO:134或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含hCG_2002731多肽或由其组成。在一些实施方案中，所述hCG_2002731包含SEQ ID NO:135或由其组成。在一些实施方案中，所述hCG_2002731多肽包含SEQ ID NO:136或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含切除修复交叉互补组1(ERCC1)多肽或由其组成。在一些实施方案中，所述ERCC1多肽包含SEQ ID NO:137或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含ras相关C3肉毒杆菌毒素底物1亚型(RAC1)多肽或由其组成。在一些实施方案中，所述RAC1多肽包含SEQ ID NO:138或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含核糖核酸酶A A1(RAA1)多肽或由其组成。在一些实施方案中，所述RAA1多肽包含SEQ ID NO:139或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含Ras相关蛋白(RAB1)多肽或由其组成。在一些实施方案中，所述RAB1多肽包含SEQ ID NO:140或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含DNA复制解旋酶/核酸酶2(DNA2)多肽或由其组成。在一些实施方案中，所述DNA2多肽包含SEQ ID NO:141或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含FLJ35220多肽或由其组成。在一些实施方案中，所述FLJ35220多肽包含SEQ ID NO:142或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含FLJ13173多肽或由其组成。在一些实施方案中，所述FLJ13173多肽包含SEQ ID NO:143或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含特诺伊林(Teneurin)跨膜蛋白(TENM)多肽或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含特诺伊林跨膜蛋白1(TENM1)多肽或由其组成。在一些实施方案中，所述TENM1多肽包含SEQ ID NO:144或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含特诺伊林跨膜蛋白2(TENM2)多肽或由其组成。在一些实施方案中，所述TENM2多肽包含SEQ ID NO:145或由其组成。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含核糖核酸酶κ(RNA酶K)多肽或由其组成。在一些实施方案中，所述RNA酶K多肽包含SEQ ID NO:204或由其组成。
在一些实施方案中，将本公开文本的融合蛋白用于治疗有需要的受试者的方法中，所述方法包括使靶RNA与融合蛋白或编码所述融合蛋白的序列接触。
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图1A-图1B是本公开文本的组合物的示例性实施方案的示意图。(A)与内切核酸酶融合的靶向RNA的Cas9系统靶向并切割引起疾病的RNA。(B)描绘了(A)在强直性肌营养不良1型的情况下的应用，其中与内切核酸酶融合的靶向RNA的Cas9系统靶向并切割由重复CUG单元构成的重复性RNA。在靶向RNA的Cas9系统不存在的情况下，由重复CUG单元构成的重复性RNA与剪接因子MBNL结合，并通过功能障碍性RNA剪接引起病状。该重复性RNA的切割改善疾病。
图2是描绘了用于通过靶向RNA分子治疗遗传疾病的示例性模块化治疗平台的示意图。
图3A-图3B是一对示意图，其描绘了(A)“高表达”对照系统(也称为“pos对照”)，所述对照系统包含双质粒系统，所述质粒系统包含驱动RNA内切核酸酶/Cas9融合物的表达的巨细胞病毒启动子；以及(B)“低表达”对照系统(也称为“P13”)，所述对照系统包含单质粒系统，所述质粒系统包含驱动RNA内切核酸酶/Cas9融合物的表达的较低表达启动子(pEFS)。
图4A是一对示意图，其描绘了示例性RNA内切核酸酶-空肠弯曲杆菌(C.jejuni)Cas9融合蛋白(左)和包含示例性RNA内切核酸酶-酿脓链球菌(S.pyogenes)Cas9融合蛋白的载体(右)。
图4B是描绘了如图4A中所示的包含空肠弯曲杆菌Cas9或酿脓链球菌Cas9的多种融合蛋白切割重复性RNA分子的能力的图。
图5A是一对示意图，其描绘了示例性RNA内切核酸酶-空肠弯曲杆菌Cas9融合蛋白(左)和包含示例性RNA内切核酸酶-酿脓链球菌Cas9融合蛋白的载体(右)。
图5B是描绘了如图5A中所示的包含空肠弯曲杆菌Cas9或酿脓链球菌Cas9的多种融合蛋白切割编码萤光素酶蛋白的mRNA分子的能力的图。
图6是提供了图4B、图5B和图9中所示的内切核酸酶的关键码的表格。
图7A是描绘了示例性RNA内切核酸酶-空肠弯曲杆菌Cas9融合蛋白的示意图。
图7B是描绘了在E43和E67CjeCas9-内切核酸酶融合物二者的存在下Zika NS5的表达水平的变化的图，所述融合物具有含有如表2中指示的各种靶向NS5的间隔子序列的sgRNA。将Zika NS5表达展示为相对于加载有含有对照(λ)间隔子序列的sgRNA的内切核酸酶的变化倍数。
图8A是用加载有含有靶向Zika NS5的间隔子序列的sgRNA的CjeCas9-内切核酸酶融合物转染的细胞的荧光显微镜检查图像。
图8B是描绘了如与加载有不靶向Zika NS5的sgRNA的CjeCas9-内切核酸酶融合物相比在加载有靶向Zika NS5的适当sgRNA的CjeCas9-内切核酸酶融合物存在下Zika NS5的表达的变化的图。
图9是描绘了各种示例性融合蛋白(与注释的内切核酸酶融合的SpyCas9)的切割效率的图。
具体实施方式
本公开文本提供了RNA指导的融合蛋白，其选择性结合并且任选地切割RNA分子。本公开文本提供了包含所述RNA指导的融合蛋白的载体、组合物和细胞。本公开文本提供了使用本公开文本的RNA指导的融合蛋白、载体、组合物和细胞治疗疾病或障碍的方法。
指导RNA
术语指导RNA(gRNA)与单一指导RNA(sgRNA)在整个本公开文本中可互换使用。
本公开文本的指导RNA(gRNA)可以包含间隔子序列和支架序列。在一些实施方案中，指导RNA是单一指导RNA(sgRNA)，其包含连续间隔子序列和支架序列。在一些实施方案中，间隔子序列和支架序列是不连续的。在一些实施方案中，支架序列包含“同向重复”(DR)序列。DR序列是指CRISPR基因座(天然存在于细菌基因组或质粒中)中的重复性序列，其中散布有间隔子序列。众所周知，如果相关CRISPR基因座的序列是已知的，则将能够推断相应Cas蛋白的DR序列。在一些实施方案中，编码本公开文本的指导RNA或单一指导RNA的序列包含由接头序列隔开的间隔子序列和支架序列或由其组成。在一些实施方案中，接头序列可以包含1、2、3、4、5、6、7、8、9、10、15、20、25、30、35、40、45、50个或之间的任何数量的核苷酸或由其组成。在一些实施方案中，接头序列可以包含至少1、2、3、4、5、6、7、8、9、10、15、20、25、30、35、40、45、50个或之间的任何数量的核苷酸。
本公开文本的指导RNA(gRNA)可以包含非天然存在的核苷酸。在一些实施方案中，本公开文本的指导RNA或编码所述指导RNA的序列包含修饰的或合成的RNA核苷酸或由其组成。示例性的修饰的RNA核苷酸包括但不限于假尿苷(Ψ)、二氢尿苷(D)、肌苷(I)、和7-甲基鸟苷(m7G)、次黄嘌呤、黄嘌呤、黄苷、7-甲基鸟嘌呤、5,6-二氢尿嘧啶、5-甲基胞嘧啶、5-甲基胞苷、5-羟甲基胞嘧啶、异鸟嘌呤和异胞嘧啶。
本公开文本的指导RNA(gRNA)可以结合靶序列内的修饰的RNA。在靶序列内，本公开文本的指导RNA(gRNA)可以结合修饰的RNA。示例性的表观遗传或转录后修饰的RNA包括但不限于2'-O-甲基化(2'-OMe)(2'-O-甲基化发生在核糖部分的游离2'-OH的氧上)、N6-甲基腺苷(m6A)和5-甲基胞嘧啶(m5C)。
在本公开文本的组合物的一些实施方案中，本公开文本的指导RNA包含编码非编码C/D盒核仁小RNA(snoRNA)序列的至少一个序列。在一些实施方案中，snoRNA序列包含与靶RNA互补的至少一个序列，其中所述RNA分子的靶序列包含至少一个2'-OMe。在一些实施方案中，snoRNA序列包含与靶RNA互补的至少一个序列，其中与靶RNA互补的所述至少一个序列包含盒C基序(RUGAUGA)和盒D基序(CUGA)。
本公开文本的间隔子序列与RNA分子的靶序列结合。本公开文本的间隔子序列可以包含CRISPR RNA(crRNA)。本公开文本的间隔子序列包含与RNA分子的靶序列具有足够互补性以与所述靶序列选择性结合的序列或由其组成。在与RNA分子的靶序列结合后，间隔子序列可以将支架序列和融合蛋白中的一种或多种指导至所述RNA分子。在一些实施方案中，与RNA分子的靶序列具有足够互补性以与所述靶序列选择性结合的序列与所述靶序列具有至少50％、55％、60％、65％、70％、75％、80％、85％、90％、95％、96、97％、98％、99％或之间的任何百分比的同一性。在一些实施方案中，与RNA分子的靶序列具有足够互补性以与所述靶序列选择性结合的序列与所述靶序列具有100％同一性。
本公开文本的支架序列结合本公开文本的第一RNA结合多肽。本公开文本的支架序列可以包含反式作用RNA(tracrRNA)。本公开文本的支架序列包含与RNA分子的靶序列具有足够互补性以与所述靶序列选择性结合的序列或由其组成。在与RNA分子的靶序列结合后，支架序列可以将融合蛋白指导至所述RNA分子。在一些实施方案中，与RNA分子的靶序列具有足够互补性以与所述靶序列选择性结合的序列与所述靶序列具有至少50％、55％、60％、65％、70％、75％、80％、85％、90％、95％、96、97％、98％、99％或之间的任何百分比的同一性。在一些实施方案中，与RNA分子的靶序列具有足够互补性以与所述靶序列选择性结合的序列与所述靶序列具有100％同一性。可替代地，或另外地，在一些实施方案中，本公开文本的支架序列包含与本公开文本的融合蛋白的第一RNA结合蛋白或第二RNA结合蛋白结合的序列或由其组成。在一些实施方案中，本公开文本的支架序列包含二级结构或三级结构。示例性二级结构包括但不限于螺旋、茎环、凸起、四环和假结。示例性三级结构包括但不限于螺旋的A形式、螺旋的B形式和螺旋的Z形式。示例性三级结构包括但不限于扭曲的或螺旋化的茎环。示例性三级结构包括但不限于扭曲的或螺旋化的假结。在一些实施方案中，本公开文本的支架序列包含至少一种二级结构或至少一种三级结构。在一些实施方案中，本公开文本的支架序列包含一种或多种二级结构或者一种或多种三级结构。
在本公开文本的组合物的一些实施方案中，指导RNA或其部分与本公开文本的RNA分子中的四环基序选择性结合。在一些实施方案中，RNA分子的靶序列包含四环基序。在一些实施方案中，四环基序是“GRNA”基序，所述基序包含GAAA、GUGA、GCAA或GAGA的序列中的一种或多种或由其组成。
在本公开文本的组合物的一些实施方案中，与RNA分子的靶序列结合的指导RNA或其部分与所述RNA分子的靶序列杂交。在一些实施方案中，与第一RNA结合蛋白或与第二RNA结合蛋白结合的指导RNA或其部分与第一RNA结合蛋白或与第二RNA结合蛋白共价结合。在一些实施方案中，与第一RNA结合蛋白或与第二RNA结合蛋白结合的指导RNA或其部分与第一RNA结合蛋白或与第二RNA结合蛋白非共价结合。
在本公开文本的组合物的一些实施方案中，指导RNA或其部分包含在10个与100个之间的核苷酸(包括端点)或由所述核苷酸组成。在一些实施方案中，本公开文本的间隔子序列包含在10个与30个之间的核苷酸(包括端点)或由其组成。在一些实施方案中，本公开文本的间隔子序列包含15、16、17、18、19、20、21、22、23、24、25、26、27、28、29或30个核苷酸或由其组成。在一些实施方案中，本公开文本的间隔子序列包含20个核苷酸或由其组成。在一些实施方案中，本公开文本的间隔子序列包含21个核苷酸或由其组成。在一些实施方案中，本公开文本的支架序列包含在10个与100个之间的核苷酸(包括端点)或由其组成。在一些实施方案中，本公开文本的支架序列包含30、35、40、45、50、55、60、65、70、76、80、87、90、95、100个或之间的任何数量的核苷酸或由其组成。在一些实施方案中，本公开文本的支架序列包含在85个与95个之间的核苷酸(包括端点)或由其组成。在一些实施方案中，本公开文本的支架序列包含85个核苷酸或由其组成。在一些实施方案中，本公开文本的支架序列包含90个核苷酸或由其组成。在一些实施方案中，本公开文本的支架序列包含93个核苷酸或由其组成。
在本公开文本的组合物的一些实施方案中，指导RNA或其部分不包含核定位序列(NLS)。
在本公开文本的组合物的一些实施方案中，指导RNA或其部分不包含与原间隔子相邻基序(PAM)互补的序列。
本公开文本的治疗或药物组合物不包含PAMmer寡核苷酸。在其他实施方案中，任选地，非治疗或非药物组合物可以包含PAMmer寡核苷酸。术语“PAMmer”是指以下寡核苷酸，其包含能够与指导核苷酸序列可编程的RNA结合蛋白相互作用的PAM序列。PAMmer的非限制性例子描述于通过引用并入本文的O'Connell等人Nature 516,第263-266页(2014)中。PAM序列是指包含约2至约10个核苷酸的原间隔子相邻基序。PAM序列对与其相互作用的指导核苷酸序列可编程的RNA结合蛋白具有特异性，并且是本领域中已知的。例如，酿脓链球菌(Streptococcus pyogenes)PAM具有序列5'-NGG-3'，其中“N”是任何核碱基，之后有两个鸟嘌呤(“G”)核碱基。新凶手弗朗西丝菌(Francisella novicida)的Cas9识别规范PAM序列5'-NGG-3'，但是已经被工程化以识别PAM 5'-YG-3'(其中“Y”是嘧啶)，从而添加至可能的Cas9靶标的范围内。新凶手弗朗西丝菌的Cpf1核酸酶识别PAM 5'-TTTN-3'或5'-YTN-3'。
在本公开文本的组合物的一些实施方案中，指导RNA或其部分包含与原间隔子侧翼序列(PFS)互补的序列。在一些实施方案(包括其中指导RNA或其部分包含与PFS互补的序列的那些实施方案)中，第一RNA结合蛋白可以包含从Cas13蛋白分离或衍生的序列。在一些实施方案(包括其中指导RNA或其部分包含与PFS互补的序列的那些实施方案)中，第一RNA结合蛋白可以包含编码Cas13蛋白或其RNA结合部分的序列。在一些实施方案中，所述指导RNA或其部分不包含与PFS互补的序列。
在本公开文本的组合物的一些实施方案中，本公开文本的指导RNA序列包含用于驱动指导RNA的表达的启动子序列。在一些实施方案中，包含本公开文本的指导RNA序列的载体包含用于驱动指导RNA的表达的启动子序列。在一些实施方案中，用于驱动指导RNA的表达的启动子是组成型启动子。在一些实施方案中，所述启动子序列是诱导型启动子。在一些实施方案中，所述启动子是序列是组织特异性和/或细胞类型特异性启动子。在一些实施方案中，所述启动子是杂合启动子或重组启动子。在一些实施方案中，所述启动子是能够在哺乳动物细胞中表达指导RNA的启动子。在一些实施方案中，所述启动子是能够在人细胞中表达指导RNA的启动子。在一些实施方案中，所述启动子是能够表达指导RNA并将指导RNA限制于细胞核的启动子。在一些实施方案中，所述启动子是人RNA聚合酶启动子或从编码人RNA聚合酶启动子的序列分离或衍生的序列。在一些实施方案中，所述启动子是U6启动子或从编码U6启动子的序列分离或衍生的序列。在一些实施方案中，所述启动子是人tRNA启动子或从编码人tRNA启动子的序列分离或衍生的序列。在一些实施方案中，所述启动子是人缬氨酸tRNA启动子或从编码人缬氨酸tRNA启动子的序列分离或衍生的序列。
在本公开文本的组合物的一些实施方案中，用于驱动指导RNA的表达的启动子还包含调节元件。在一些实施方案中，包含用于驱动指导RNA的表达的启动子序列的载体还包含调节元件。在一些实施方案中，调节元件增强指导RNA的表达。示例性调节元件包括但不限于增强子元件、内含子、外显子或其组合。
在本公开文本的组合物的一些实施方案中，本公开文本的载体包含编码指导RNA的序列、用于驱动指导RNA的表达的启动子序列和编码调节元件的序列中的一种或多种。在本公开文本的组合物的一些实施方案中，所述载体还包含编码本公开文本的融合蛋白的序列。
融合蛋白
本公开文本的融合蛋白包含第一RNA结合蛋白和第二RNA结合蛋白。在一些实施方案中，沿着编码融合蛋白的序列，编码第一RNA结合蛋白的序列定位于编码第二RNA结合蛋白的序列的5'。在一些实施方案中，沿着编码融合蛋白的序列，编码第一RNA结合蛋白的序列定位于编码第二RNA结合蛋白的序列的3'。
在本公开文本的组合物的一些实施方案中，编码第一RNA结合蛋白的序列包含从蛋白质分离或衍生的序列，所述蛋白质能够结合RNA分子。在一些实施方案中，编码第一RNA结合蛋白的序列包含从蛋白质分离或衍生的序列，所述蛋白质能够选择性结合RNA分子，并且不结合DNA分子、哺乳动物DNA分子或任何DNA分子。在一些实施方案中，编码第一RNA结合蛋白的序列包含从蛋白质分离或衍生的序列，所述蛋白质能够结合RNA分子，并且诱导所述RNA分子中的断裂。在一些实施方案中，编码第一RNA结合蛋白的序列包含从蛋白质分离或衍生的序列，所述蛋白质能够结合RNA分子，诱导所述RNA分子中的断裂，并且不结合DNA分子、哺乳动物DNA分子或任何DNA分子。在一些实施方案中，编码第一RNA结合蛋白的序列包含从蛋白质分离或衍生的序列，所述蛋白质能够结合RNA分子，诱导所述RNA分子中的断裂，并且既不结合DNA分子、哺乳动物DNA分子或任何DNA分子，也不诱导所述DNA分子中的断裂。
在本公开文本的组合物的一些实施方案中，编码第一RNA结合蛋白的序列包含从没有DNA核酸酶活性的蛋白质分离或衍生的序列。
在本公开文本的组合物的一些实施方案中，编码第一RNA结合蛋白的序列包含从具有DNA核酸酶活性的蛋白质分离或衍生的序列，其中在将本公开文本的组合物与RNA分子接触或引入本公开文本的细胞中或受试者体内时，所述DNA核酸酶活性不诱导DNA分子、哺乳动物DNA分子或任何DNA分子中的断裂。
在本公开文本的组合物的一些实施方案中，编码第一RNA结合蛋白的序列包含从具有DNA核酸酶活性的蛋白质分离或衍生的序列，其中所述DNA核酸酶活性是失活的，并且其中在将本公开文本的组合物与RNA分子接触或引入本公开文本的细胞中或受试者体内时，所述DNA核酸酶活性不诱导DNA分子、哺乳动物DNA分子或任何DNA分子中的断裂。在一些实施方案中，编码第一RNA结合蛋白的序列包含使DNA核酸酶活性失活或降低至以下水平的突变，在所述水平下，在将本公开文本的组合物与RNA分子接触或引入本公开文本的细胞中或受试者体内时，所述DNA核酸酶活性不诱导DNA分子、哺乳动物DNA分子或任何DNA分子中的断裂。在一些实施方案中，编码第一RNA结合蛋白的序列包含使DNA核酸酶活性失活或降低的突变，并且所述突变包含对编码第一RNA结合蛋白或其核酸酶结构域的核酸序列或氨基酸序列的取代、倒位、转座、插入、缺失或其任何组合中的一种或多种。
在本公开文本的组合物的一些实施方案中，编码本文公开的RNA指导的融合蛋白的第一RNA结合蛋白的序列包含从CRISPR Cas蛋白分离或衍生的序列。在一些实施方案中，所述CRISPR Cas蛋白包含II型CRISPR Cas蛋白。在一些实施方案中，所述II型CRISPR Cas蛋白包含Cas9蛋白。本公开文本的示例性Cas9蛋白可以从任何物种分离或衍生，所述物种包括但不限于细菌或古菌。本公开文本的示例性Cas9蛋白可以从任何物种分离或衍生，所述物种包括但不限于酿脓链球菌、地中海富盐菌(Haloferax mediteranii)、结核分枝杆菌(Mycobacterium tuberculosis)、土拉热弗朗西丝菌新凶手亚种(Francisellatularensis subsp.novicida)、多杀巴斯德菌(Pasteurella multocida)、脑膜炎奈瑟球菌(Neisseria meningitidis)、空肠弯曲杆菌(Campylobacter jejune)、嗜热链球菌(Streptococcus thermophilus)、红嘴鸥弯曲杆菌CF89-12(Campylobacter lari CF89-12)、鸡毒支原体F株(Mycoplasma gallisepticum str.F)、卤水硝酸盐裂解菌DSM 16511株(Nitratifractor salsuginis str.DSM 16511)、食清洁剂细小棒菌(Parvibaculumlavamentivorans)、肠道罗斯拜瑞氏菌(Roseburia intestinalis)、灰色奈瑟球菌(Neisseria cinerea)、重氮营养葡糖酸醋杆菌(Gluconacetobacter diazotrophicus)、固氮螺菌(Azospirillum)B510、球状螺旋菌巴迪株(Sphaerochaeta globus str.Buddy)、柱状黄杆菌(Flavobacterium columnare)、塔夫河栖河菌(Fluviicola taffensis)、嗜粪拟杆菌(Bacteroides coprophilus)、运动支原体(Mycoplasma mobile)、香肠乳杆菌(Lactobacillus farciminis)、巴氏链球菌(Streptococcus pasteurianus)、约氏乳杆菌(Lactobacillus johnsonii)、伪中间型葡萄球菌(Staphylococcus pseudintermedius)、龈沟产线菌(Filifactor alocis)、齿垢密螺旋体(Treponema denticola)、嗜肺军团菌巴黎株(Legionella pneumophila str.Paris)、华德萨特氏菌(Sutterellawadsworthensis)、白喉棒状杆菌(Corynebacter diphtherias)、金黄色葡萄球菌(Streptococcus aureus)和新凶手弗朗西丝菌。
本公开文本的示例性的野生型酿脓链球菌Cas9蛋白可以包含以下氨基酸序列或由其组成：
Figure BDA0002919433300000211
核酸酶失活的酿脓链球菌Cas9蛋白可以包含丙氨酸(A)取代位置10的天冬氨酸(D)以及丙氨酸(A)取代位置840的组氨酸(H)。本公开文本的示例性的核酸酶失活的酿脓链球菌Cas9蛋白可以包含以下氨基酸序列或由其组成(D10A和H840A加粗并加下划线)：
Figure BDA0002919433300000212
Figure BDA0002919433300000221
核酸酶失活的酿脓链球菌Cas9蛋白可以包含RuvC核酸酶结构域或其部分、HNH结构域、DNA酶活性位点、包含DNA酶活性位点的ββα-金属折叠或其部分或者其任何组合的缺失。
其他示例性Cas9蛋白或其部分可以包含以下氨基酸序列或由所述氨基酸序列组成。
在一些实施方案中，所述Cas9蛋白可以是酿脓链球菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD(SEQ ID NO:149)
在一些实施方案中，所述Cas9蛋白可以是金黄色葡萄球菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MKRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRRRHRIQRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHNVNEVEEDTGNELSTKEQISRNSKALEEKYVAELQLERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQLDQSFIDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAYNADLYNALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIAKEILVNEEDIKGYRVTSTGKPEFTNLKVYHDIKDITARKEIIENAELLDQIAKILTIYQSSEDIQEELTNLNSELTQEEIEQISNLKGYTGTHNLSLKAINLILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSPVVKRSFIQSIKVINAIIKKYGLPNDIIIELAREKNSKDAQKMINEMQKRNRQTNERIEEIIRTTGKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDHIIPRSVSFDNSFNNKVLVKQEENSKKGNRTPFQYLSSSDSKISYETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQKDFINRNLVDTRYATRGLMNLLRSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHHAEDALIIANADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDFKDYKYSHRVDKKPNRELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHHDPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDDYPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKISNQAEFIASFYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRIIKTIASKTQSIKKYSTDILGNLYEVKSKKHPQIIKKG(SEQID NO:150)
在一些实施方案中，所述Cas9蛋白可以是嗜热链球菌CRISPR1Cas9，并且可以包含以下氨基酸序列或由其组成：
MSDLVLGLDIGIGSVGVGILNKVTGEIIHKNSRIFPAAQAENNLVRRTNRQGRRLARRKKHRRVRLNRLFEESGLITDFTKISINLNPYQLRVKGLTDELSNEELFIALKNMVKHRGISYLDDASDDGNSSVGDYAQIVKENSKQLETKTPGQIQLERYQTYGQLRGDFTVEKDGKKHRLINVFPTSAYRSEALRILQTQQEFNPQITDEFINRYLEILTGKRKYYHGPGNEKSRTDYGRYRTSGETLDNIFGILIGKCTFYPDEFRAAKASYTAQEFNLLNDLNNLTVPTETKKLSKEQKNQIINYVKNEKAMGPAKLFKYIAKLLSCDVADIKGYRIDKSGKAEIHTFEAYRKMKTLETLDIEQMDRETLDKLAYVLTLNTEREGIQEALEHEFADGSFSQKQVDELVQFRKANSSIFGKGWHNFSVKLMMELIPELYETSEEQMTILTRLGKQKTTSSSNKTKYIDEKLLTEEIYNPVVAKSVRQAIKIVNAAIKEYGDFDNIVIEMARETNEDDEKKAIQKIQKANKDEKDAAMLKAANQYNGKAELPHSVFHGHKQLATKIRLWHQQGERCLYTGKTISIHDLINNSNQFEVDHILPLSITFDDSLANKVLVYATANQEKGQRTPYQALDSMDDAWSFRELKAFVRESKTLSNKKKEYLLTEEDISKFDVRKKFIERNLVDTRYASRVVLNALQEHFRAHKIDTKVSVVRGQFTSQLRRHWGIEKTRDTYHHHAVDALIIAASSQLNLWKKQKNTLVSYSEDQLLDIETGELISDDEYKESVFKAPYQHFVDTLKSKEFEDSILFSYQVDSKFNRKISDATIYATRQAKVGKDKADETYVLGKIKDIYTQDGYDAFMKIYKKDKSKFLMYRHDPQTFEKVIEPILENYPNKQINDKGKEVPCNPFLKYKEEHGYIRKYSKKGNGPEIKSLKYYDSKLGNHIDITPKDSNNKVVLQSVSPWRADVYFNKTTGKYEILGLKYADLQFDKGTGTYKISQEKYNDIKKKEGVDSDSEFKFTLYKNDLLLVKDTETKEQQLFRFLSRTMPKQKHYVELKPYDKQKFEGGEALIKVLGNVANSGQCKKGLGKSNISIYKVRTDVLGNQHIIKNEGDKPKLDF(SEQ ID NO:151)
在一些实施方案中，所述Cas9蛋白可以是脑膜炎奈瑟球菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MAAFKPNPINYILGLDIGIASVGWAMVEIDEDENPICLIDLGVRVFERAEVPKTGDSLAMARRLARSVRRLTRRRAHRLLRARRLLKREGVLQAADFDENGLIKSLPNTPWQLRAAALDRKLTPLEWSAVLLHLIKHRGYLSQRKNEGETADKELGALLKGVADNAHALQTGDFRTPAELALNKFEKESGHIRNQRGDYSHTFSRKDLQAELILLFEKQKEFGNPHVSGGLKEGIETLLMTQRPALSGDAVQKMLGHCTFEPAEPKAAKNTYTAERFIWLTKLNNLRILEQGSERPLTDTERATLMDEPYRKSKLTYAQARKLLGLEDTAFFKGLRYGKDNAEASTLMEMKAYHAISRALEKEGLKDKKSPLNLSPELQDEIGTAFSLFKTDEDITGRLKDRIQPEILEALLKHISFDKFVQISLKALRRIVPLMEQGKRYDEACAEIYGDHYGKKNTEEKIYLPPIPADEIRNPVVLRALSQARKVINGVVRRYGSPARIHIETAREVGKSFKDRKEIEKRQEENRKDREKAAAKFREYFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLGRLNEKGYVEIDHALPFSRTWDDSFNNKVLVLGSENQNKGNQTPYEYFNGKDNSREWQEFKARVETSRFPRSKKQRILLQKFDEDGFKERNLNDTRYVNRFLCQFVADRMRLTGKGKKRVFASNGQITNLLRGFWGLRKVRAENDRHHALDAVVVACSTVAMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQKTHFPQPWEFFAQEVMIRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHEYVTPLFVSRAPNRKMSGQGHMETVKSAKRLDEGVSVLRVPLTQLKLKDLEKMVNREREPKLYEALKARLEAHKDDPAKAFAEPFYKYDKAGNRTQQVKAVRVEQVQKTGVWVRNHNGIADNATMVRVDVFEKGDKYYLVPIYSWQVAKGILPDRAVVQGKDEEDWQLIDDSFNFKFSLHPNDLVEVITKKARMFGYFASCHRGTGNINIRIHDLDHKIGKNGILEGIGVKTALSFQKYQIDELGKEIRPCRLKKRPPVR(SEQ ID NO:152)
在一些实施方案中，所述Cas9蛋白可以是食清洁剂细小棒菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MERIFGFDIGTTSIGFSVIDYSSTQSAGNIQRLGVRIFPEARDPDGTPLNQQRRQKRMMRRQLRRRRIRRKALNETLHEAGFLPAYGSADWPVVMADEPYELRRRGLEEGLSAYEFGRAIYHLAQHRHFKGRELEESDTPDPDVDDEKEAANERAATLKALKNEQTTLGAWLARRPPSDRKRGIHAHRNVVAEEFERLWEVQSKFHPALKSEEMRARISDTIFAQRPVFWRKNTLGECRFMPGEPLCPKGSWLSQQRRMLEKLNNLAIAGGNARPLDAEERDAILSKLQQQASMSWPGVRSALKALYKQRGEPGAEKSLKFNLELGGESKLLGNALEAKLADMFGPDWPAHPRKQEIRHAVHERLWAADYGETPDKKRVIILSEKDRKAHREAAANSFVADFGITGEQAAQLQALKLPTGWEPYSIPALNLFLAELEKGERFGALVNGPDWEGWRRTNFPHRNQPTGEILDKLPSPASKEERERISQLRNPTVVRTQNELRKVVNNLIGLYGKPDRIRIEVGRDVGKSKREREEIQSGIRRNEKQRKKATEDLIKNGIANPSRDDVEKWILWKEGQERCPYTGDQIGFNALFREGRYEVEHIWPRSRSFDNSPRNKTLCRKDVNIEKGNRMPFEAFGHDEDRWSAIQIRLQGMVSAKGGTGMSPGKVKRFLAKTMPEDFAARQLNDTRYAAKQILAQLKRLWPDMGPEAPVKVEAVTGQVTAQLRKLWTLNNILADDGEKTRADHRHHAIDALTVACTHPGMTNKLSRYWQLRDDPRAEKPALTPPWDTIRADAEKAVSEIVVSHRVRKKVSGPLHKETTYGDTGTDIKTKSGTYRQFVTRKKIESLSKGELDEIRDPRIKEIVAAHVAGRGGDPKKAFPPYPCVSPGGPEIRKVRLTSKQQLNLMAQTGNGYADLGSNHHIAIYRLPDGKADFEIVSLFDASRRLAQRNPIVQRTRADGASFVMSLAAGEAIMIPEGSKKGIWIVQGVWASGQVVLERDTDADHSTTTRPMPNPILKDDAKKVSIDPIGRVRPSND(SEQ ID NO:153)
在一些实施方案中，所述Cas9蛋白可以是白喉棒状杆菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MKYHVGIDVGTFSVGLAAIEVDDAGMPIKTLSLVSHIHDSGLDPDEIKSAVTRLASSGIARRTRRLYRRKRRRLQQLDKFIQRQGWPVIELEDYSDPLYPWKVRAELAASYIADEKERGEKLSVALRHIARHRGWRNPYAKVSSLYLPDGPSDAFKAIREEIKRASGQPVPETATVGQMVTLCELGTLKLRGEGGVLSARLQQSDYAREIQEICRMQEIGQELYRKIIDVVFAAESPKGSASSRVGKDPLQPGKNRALKASDAFQRYRIAALIGNLRVRVDGEKRILSVEEKNLVFDHLVNLTPKKEPEWVTIAEILGIDRGQLIGTATMTDDGERAGARPPTHDTNRSIVNSRIAPLVDWWKTASALEQHAMVKALSNAEVDDFDSPEGAKVQAFFADLDDDVHAKLDSLHLPVGRAAYSEDTLVRLTRRMLSDGVDLYTARLQEFGIEPSWTPPTPRIGEPVGNPAVDRVLKTVSRWLESATKTWGAPERVIIEHVREGFVTEKRAREMDGDMRRRAARNAKLFQEMQEKLNVQGKPSRADLWRYQSVQRQNCQCAYCGSPITFSNSEMDHIVPRAGQGSTNTRENLVAVCHRCNQSKGNTPFAIWAKNTSIEGVSVKEAVERTRHWVTDTGMRSTDFKKFTKAVVERFQRATMDEEIDARSMESVAWMANELRSRVAQHFASHGTTVRVYRGSLTAEARRASGISGKLKFFDGVGKSRLDRRHHAIDAAVIAFTSDYVAETLAVRSNLKQSQAHRQEAPQWREFTGKDAEHRAAWRVWCQKMEKLSALLTEDLRDDRVVVMSNVRLRLGNGSAHKETIGKLSKVKLSSQLSVSDIDKASSEALWCALTREPGFDPKEGLPANPERHIRVNGTHVYAGDNIGLFPVSAGSIALRGGYAELGSSFHHARVYKITSGKKPAFAMLRVYTIDLLPYRNQDLFSVELKPQTMSMRQAEKKLRDALATGNAEYLGWLVVDDELVVDTSKIATDQVKAVEAELGTIRRWRVDGFFSPSKLRLRPLQMSKEGIKKESAPELSKIIDRPGWLPAVNKLFSDGNVTVVRRDSLGRVRLESTAHLPVTWKVQ(SEQ ID NO:154)
在一些实施方案中，所述Cas9蛋白可以是巴氏链球菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MTNGKILGLDIGIASVGVGIIEAKTGKVVHANSRLFSAANAENNAERRGFRGSRRLNRRKKHRVKRVRDLFEKYGIVTDFRNLNLNPYELRVKGLTEQLKNEELFAALRTISKRRGISYLDDAEDDSTGSTDYAKSIDENRRLLKNKTPGQIQLERLEKYGQLRGNFTVYDENGEAHRLINVFSTSDYEKEARKILETQADYNKKITAEFIDDYVEILTQKRKYYHGPGNEKSRTDYGRFRTDGTTLENIFGILIGKCNFYPDEYRASKASYTAQEYNFLNDLNNLKVSTETGKLSTEQKESLVEFAKNTATLGPAKLLKEIAKILDCKVDEIKGYREDDKGKPDLHTFEPYRKLKFNLESINIDDLSREVIDKLADILTLNTEREGIEDAIKRNLPNQFTEEQISEIIKVRKSQSTAFNKGWHSFSAKLMNELIPELYATSDEQMTILTRLEKFKVNKKSSKNTKTIDEKEVTDEIYNPVVAKSVRQTIKIINAAVKKYGDFDKIVIEMPRDKNADDEKKFIDKRNKENKKEKDDALKRAAYLYNSSDKLPDEVFHGNKQLETKIRLWYQQGERCLYSGKPISIQELVHNSNNFEIDHILPLSLSFDDSLANKVLVYAWTNQEKGQKTPYQVIDSMDAAWSFREMKDYVLKQKGLGKKKRDYLLTTENIDKIEVKKKFIERNLVDTRYASRVVLNSLQSALRELGKDTKVSVVRGQFTSQLRRKWKIDKSRETYHHHAVDALIIAASSQLKLWEKQDNPMFVDYGKNQVVDKQTGEILSVSDDEYKELVFQPPYQGFVNTISSKGFEDEILFSYQVDSKYNRKVSDATIYSTRKAKIGKDKKEETYVLGKIKDIYSQNGFDTFIKKYNKDKTQFLMYQKDSLTWENVIEVILRDYPTTKKSEDGKNDVKCNPFEEYRRENGLICKYSKKGKGTPIKSLKYYDKKLGNCIDITPEESRNKVILQSINPWRADVYFNPETLKYELMGLKYSDLSFEKGTGNYHISQEKYDAIKEKEGIGKKSEFKFTLYRNDLILIKDIASGEQEIYRFLSRTMPNVNHYVELKPYDKEKFDNVQELVEALGEADKVGRCIKGLNKPNISIYKVRTDVLGNKYFVKKKGDKPKLDFKNNKK(SEQ ID NO:155)
在一些实施方案中，所述Cas9蛋白可以是灰色奈瑟球菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MAAFKPNPMNYILGLDIGIASVGWAIVEIDEEENPIRLIDLGVRVFERAEVPKTGDSLAAARRLARSVRRLTRRRAHRLLRARRLLKREGVLQAADFDENGLIKSLPNTPWQLRAAALDRKLTPLEWSAVLLHLIKHRGYLSQRKNEGETADKELGALLKGVADNTHALQTGDFRTPAELALNKFEKESGHIRNQRGDYSHTFNRKDLQAELNLLFEKQKEFGNPHVSDGLKEGIETLLMTQRPALSGDAVQKMLGHCTFEPTEPKAAKNTYTAERFVWLTKLNNLRILEQGSERPLTDTERATLMDEPYRKSKLTYAQARKLLDLDDTAFFKGLRYGKDNAEASTLMEMKAYHAISRALEKEGLKDKKSPLNLSPELQDEIGTAFSLFKTDEDITGRLKDRVQPEILEALLKHISFDKFVQISLKALRRIVPLMEQGNRYDEACTEIYGDHYGKKNTEEKIYLPPIPADEIRNPVVLRALSQARKVINGVVRRYGSPARIHIETAREVGKSFKDRKEIEKRQEENRKDREKSAAKFREYFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLGRLNEKGYVEIDHALPFSRTWDDSFNNKVLALGSENQNKGNQTPYEYFNGKDNSREWQEFKARVETSRFPRSKKQRILLQKFDEDGFKERNLNDTRYINRFLCQFVADHMLLTGKGKRRVFASNGQITNLLRGFWGLRKVRAENDRHHALDAVVVACSTIAMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQKAHFPQPWEFFAQEVMIRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHKYVTPLFISRAPNRKMSGQGHMETVKSAKRLDEGISVLRVPLTQLKLKDLEKMVNREREPKLYEALKARLEAHKDDPAKAFAEPFYKYDKAGNRTQQVKAVRVEQVQKTGVWVHNHNGIADNATIVRVDVFEKGGKYYLVPIYSWQVAKGILPDRAVVQGKDEEDWTVMDDSFEFKFVLYANDLIKLTAKKNEFLGYFVSLNRATGAIDIRTHDTDSTKGKNGIFQSVGVKTALSFQKYQIDELGKEIRPCRLKKRPPVR(SEQ ID NO:156)
在一些实施方案中，所述Cas9蛋白可以是红嘴鸥弯曲杆菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MRILGFDIGINSIGWAFVENDELKDCGVRIFTKAENPKNKESLALPRRNARSSRRRLKRRKARLIAIKRILAKELKLNYKDYVAADGELPKAYEGSLASVYELRYKALTQNLETKDLARVILHIAKHRGYMNKNEKKSNDAKKGKILSALKNNALKLENYQSVGEYFYKEFFQKYKKNTKNFIKIRNTKDNYNNCVLSSDLEKELKLILEKQKEFGYNYSEDFINEILKVAFFQRPLKDFSHLVGACTFFEEEKRACKNSYSAWEFVALTKIINEIKSLEKISGEIVPTQTINEVLNLILDKGSITYKKFRSCINLHESISFKSLKYDKENAENAKLIDFRKLVEFKKALGVHSLSRQELDQISTHITLIKDNVKLKTVLEKYNLSNEQINNLLEIEFNDYINLSFKALGMILPLMREGKRYDEACEIANLKPKTVDEKKDFLPAFCDSIFAHELSNPVVNRAISEYRKVLNALLKKYGKVHKIHLELARDVGLSKKAREKIEKEQKENQAVNAWALKECENIGLKASAKNILKLKLWKEQKEICIYSGNKISIEHLKDEKALEVDHIYPYSRSFDDSFINKVLVFTKENQEKLNKTPFEAFGKNIEKWSKIQTLAQNLPYKKKNKILDENFKDKQQEDFISRNLNDTRYIATLIAKYTKEYLNFLLLSENENANLKSGEKGSKIHVQTISGMLTSVLRHTWGFDKKDRNNHLHHALDAIIVAYSTNSIIKAFSDFRKNQELLKARFYAKELTSDNYKHQVKFFEPFKSFREKILSKIDEIFVSKPPRKRARRALHKDTFHSENKIIDKCSYNSKEGLQIALSCGRVRKIGTKYVENDTIVRVDIFKKQNKFYAIPIYAMDFALGILPNKIVITGKDKNNNPKQWQTIDESYEFCFSLYKNDLILLQKKNMQEPEFAYYNDFSISTSSICVEKHDNKFENLTSNQKLLFSNAKEGSVKVESLGIQNLKVFEKYIITPLGDKIKADFQPRENISLKTSKKYGLR(SEQ ID NO:157)
在一些实施方案中，所述Cas9蛋白可以是齿垢密螺旋体Cas9，并且可以包含以下氨基酸序列或由其组成：
MKKEIKDYFLGLDVGTGSVGWAVTDTDYKLLKANRKDLWGMRCFETAETAEVRRLHRGARRRIERRKKRIKLLQELFSQEIAKTDEGFFQRMKESPFYAEDKTILQENTLFNDKDFADKTYHKAYPTINHLIKAWIENKVKPDPRLLYLACHNIIKKRGHFLFEGDFDSENQFDTSIQALFEYLREDMEVDIDADSQKVKEILKDSSLKNSEKQSRLNKILGLKPSDKQKKAITNLISGNKINFADLYDNPDLKDAEKNSISFSKDDFDALSDDLASILGDSFELLLKAKAVYNCSVLSKVIGDEQYLSFAKVKIYEKHKTDLTKLKNVIKKHFPKDYKKVFGYNKNEKNNNNYSGYVGVCKTKSKKLIINNSVNQEDFYKFLKTILSAKSEIKEVNDILTEIETGTFLPKQISKSNAEIPYQLRKMELEKILSNAEKHFSFLKQKDEKGLSHSEKIIMLLTFKIPYYIGPINDNHKKFFPDRCWVVKKEKSPSGKTTPWNFFDHIDKEKTAEAFITSRTNFCTYLVGESVLPKSSLLYSEYTVLNEINNLQIIIDGKNICDIKLKQKIYEDLFKKYKKITQKQISTFIKHEGICNKTDEVIILGIDKECTSSLKSYIELKNIFGKQVDEISTKNMLEEIIRWATIYDEGEGKTILKTKIKAEYGKYCSDEQIKKILNLKFSGWGRLSRKFLETVTSEMPGFSEPVNIITAMRETQNNLMELLSSEFTFTENIKKINSGFEDAEKQFSYDGLVKPLFLSPSVKKMLWQTLKLVKEISHITQAPPKKIFIEMAKGAELEPARTKTRLKILQDLYNNCKNDADAFSSEIKDLSGKIENEDNLRLRSDKLYLYYTQLGKCMYCGKPIEIGHVFDTSNYDIDHIYPQSKIKDDSISNRVLVCSSCNKNKEDKYPLKSEIQSKQRGFWNFLQRNNFISLEKLNRLTRATPISDDETAKFIARQLVETRQATKVAAKVLEKMFPETKIVYSKAETVSMFRNKFDIVKCREINDFHHAHDAYLNIVVGNVYNTKFTNNPWNFIKEKRDNPKIADTYNYYKVFDYDVKRNNITAWEKGKTIITVKDMLKRNTPIYTRQAACKKGELFNQTIMKKGLGQHPLKKEGPFSNISKYGGYNKVSAAYYTLIEYEEKGNKIRSLETIPLYLVKDIQKDQDVLKSYLTDLLGKKEFKILVPKIKINSLLKINGFPCHITGKTNDSFLLRPAVQFCCSNNEVLYFKKIIRFSEIRSQREKIGKTISPYEDLSFRSYIKENLWKKTKNDEIGEKEFYDLLQKKNLEIYDMLLTKHKDTIYKKRPNSATIDILVKGKEKFKSLIIENQFEVILEILKLFSATRNVSDLQHIGGSKYSGVAKIGNKISSLDNCILIYQSITGIFEKRIDLLKV(SEQ ID NO:158)
在一些实施方案中，所述Cas9蛋白可以是变形链球菌(S.mutans)Cas9，并且可以包含以下氨基酸序列或由其组成：
MKKPYSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTAEDRRLKRTARRRYTRRRNRILYLQEIFSEEMGKVDDSFFHRLEDSFLVTEDKRGERHPIFGNLEEEVKYHENFPTIYHLRQYLADNPEKVDLRLVYLALAHIIKFRGHFLIEGKFDTRNNDVQRLFQEFLAVYDNTFENSSLQEQNVQVEEILTDKISKSAKKDRVLKLFPNEKSNGRFAEFLKLIVGNQADFKKHFELEEKAPLQFSKDTYEEELEVLLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVGTKAPLSASMIQRYNEHQMDLAQLKQFIRQKLSDKYNEVFSDVSKDGYAGYIDGKTNQEAFYKYLKGLLNKIEGSGYFLDKIEREDFLRKQRTFDNGSIPHQIHLQEMRAIIRRQAEFYPFLADNQDRIEKLLTFRIPYYVGPLARGKSDFAWLSRKSADKITPWNFDEIVDKESSAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKTEQGKTAFFDANMKQEIFDGVFKVYRKVTKDKLMDFLEKEFDEFRIVDLTGLDKENKVFNASYGTYHDLCKILDKDFLDNSKNEKILEDIVLTLTLFEDREMIRKRLENYSDLLTKEQVKKLERRHYTGWGRLSAELIHGIRNKESRKTILDYLIDDGNSNRNFMQLINDDALSFKEEIAKAQVIGETDNLNQVVSDIAGSPAIKKGILQSLKIVDELVKIMGHQPENIVVEMARENQFTNQGRRNSQQRLKGLTDSIKEFGSQILKEHPVENSQLQNDRLFLYYLQNGRDMYTGEELDIDYLSQYDIDHIIPQAFIKDNSIDNRVLTSSKENRGKSDDVPSKDVVRKMKSYWSKLLSAKLITQRKFDNLTKAERGGLTDDDKAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIRQVKIVTLKSNLVSNFRKEFELYKVREINDYHHAHDAYLNAVIGKALLGVYPQLEPEFVYGDYPHFHGHKENKATAKKFFYSNIMNFFKKDDVRTDKNGEIIWKKDEHISNIKKVLSYPQVNIVKKVEEQTGGFSKESILPKGNSDKLIPRKTKKFYWDTKKYGGFDSPIVAYSILVIADIEKGKSKKLKTVKALVGVTIMEKMTFERDPVAFLERKGYRNVQEENIIKLPKYSLFKLENGRKRLLASARELQKGNEIVLPNHLGTLLYHAKNIHKVDEPKHLDYVDKHKDEFKELLDVVSNFSKKYTLAEGNLEKIKELYAQNNGEDLKELASSFINLLTFTAIGAPATFKFFDKNIDRKRYTSTTEILNATLIHQSITGLYETRIDLNKLGGD(SEQ ID NO:159)
在一些实施方案中，所述Cas9蛋白可以是嗜热链球菌CRISPR 3Cas9，并且可以包含以下氨基酸序列或由其组成：
MTKPYSIGLDIGTNSVGWAVTTDNYKVPSKKMKVLGNTSKKYIKKNLLGVLLFDSGITAEGRRLKRTARRRYTRRRNRILYLQEIFSTEMATLDDAFFQRLDDSFLVPDDKRDSKYPIFGNLVEEKAYHDEFPTIYHLRKYLADSTKKADLRLVYLALAHMIKYRGHFLIEGEFNSKNNDIQKNFQDFLDTYNAIFESDLSLENSKQLEEIVKDKISKLEKKDRILKLFPGEKNSGIFSEFLKLIVGNQADFRKCFNLDEKASLHFSKESYDEDLETLLGYIGDDYSDVFLKAKKLYDAILLSGFLTVTDNETEAPLSSAMIKRYNEHKEDLALLKEYIRNISLKTYNEVFKDDTKNGYAGYIDGKTNQEDFYVYLKKLLAEFEGADYFLEKIDREDFLRKQRTFDNGSIPYQIHLQEMRAILDKQAKFYPFLAKNKERIEKILTFRIPYYVGPLARGNSDFAWSIRKRNEKITPWNFEDVIDKESSAEAFINRMTSFDLYLPEEKVLPKHSLLYETFNVYNELTKVRFIAESMRDYQFLDSKQKKDIVRLYFKDKRKVTDKDIIEYLHAIYGYDGIELKGIEKQFNSSLSTYHDLLNIINDKEFLDDSSNEAIIEEIIHTLTIFEDREMIKQRLSKFENIFDKSVLKKLSRRHYTGWGKLSAKLINGIRDEKSGNTILDYLIDDGISNRNFMQLIHDDALSFKKKIQKAQIIGDEDKGNIKEVVKSLPGSPAIKKGILQSIKIVDELVKVMGGRKPESIVVEMARENQYTNQGKSNSQQRLKRLEKSLKELGSKILKENIPAKLSKIDNNALQNDRLYLYYLQNGKDMYTGDDLDIDRLSNYDIDHIIPQAFLKDNSIDNKVLVSSASNRGKSDDVPSLEVVKKRKTFWYQLLKSKLISQRKFDNLTKAERGGLSPEDKAGFIQRQLVETRQITKHVARLLDEKFNNKKDENNRAVRTVKIITLKSTLVSQFRKDFELYKVREINDFHHAHDAYLNAVVASALLKKYPKLEPEFVYGDYPKYNSFRERKSATEKVYFYSNIMNIFKKSISLADGRVIERPLIEVNEETGESVWNKESDLATVRRVLSYPQVNVVKKVEEQNHGLDRGKPKGLFNANLSSKPKPNSNENLVGAKEYLDPKKYGGYAGISNSFTVLVKGTIEKGAKKKITNVLEFQGISILDRINYRKDKLNFLLEKGYKDIELIIELPKYSLFELSDGSRRMLASILSTNNKRGEIHKGNQIFLSQKFVKLLYHAKRISNTINENHRKYVENHKKEFEELFYYILEFNENYVGAKKNGKLLNSAFQSWQNHSIDELCSSFIGPTGSERKGLFELTSRGSAADFEFLGVKIPRYRDYTPSSLLKDATLIHQSVTGLYETRIDLAKLGEG(SEQ ID NO:160)
在一些实施方案中，所述Cas9蛋白可以是空肠弯曲杆菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MARILAFDIGISSIGWAFSENDELKDCGVRIFTKVENPKTGESLALPRRLARSARKRLARRKARLNHLKHLIANEFKLNYEDYQSFDESLAKAYKGSLISPYELRFRALNELLSKQDFARVILHIAKRRGYDDIKNSDDKEKGAILKAIKQNEEKLANYQSVGEYLYKEYFQKFKENSKEFTNVRNKKESYERCIAQSFLKDELKLIFKKQREFGFSFSKKFEEEVLSVAFYKRALKDFSHLVGNCSFFTDEKRAPKNSPLAFMFVALTRIINLLNNLKNTEGILYTKDDLNALLNEVLKNGTLTYKQTKKLLGLSDDYEFKGEKGTYFIEFKKYKEFIKALGEHNLSQDDLNEIAKDITLIKDEIKLKKALAKYDLNQNQIDSLSKLEFKDHLNISFKALKLVTPLMLEGKKYDEACNELNLKVAINEDKKDFLPAFNETYYKDEVTNPVVLRAIKEYRKVLNALLKKYGKVHKINIELAREVGKNHSQRAKIEKEQNENYKAKKDAELECEKLGLKINSKNILKLRLFKEQKEFCAYSGEKIKISDLQDEKMLEIDHIYPYSRSFDDSYMNKVLVFTKQNQEKLNQTPFEAFGNDSAKWQKIEVLAKNLPTKKQKRILDKNYKDKEQKNFKDRNLNDTRYIARLVLNYTKDYLDFLPLSDDENTKLNDTQKGSKVHVEAKSGMLTSALRHTWGFSAKDRNNHLHHAIDAVIIAYANNSIVKAFSDFKKEQESNSAELYAKKISELDYKNKRKFFEPFSGFRQKVLDKIDEIFVSKPERKKPSGALHEETFRKEEEFYQSYGGKEGVLKALELGKIRKVNGKIVKNGDMFRVDIFKHKKTNKFYAVPIYTMDFALKVLPNKAVARSKKGEIKDWILMDENYEFCFSLYKDSLILIQTKDMQEPEFVYYNAFTSSTVSLIVSKHDNKFETLSKNQKILFKNANEKEVIAKSIGIQNLKVFEKYIVSALGEVTKAEFRQREDFKK(SEQ ID NO:161)
在一些实施方案中，所述Cas9蛋白可以是多杀巴斯德菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MQTTNLSYILGLDLGIASVGWAVVEINENEDPIGLIDVGVRIFERAEVPKTGESLALSRRLARSTRRLIRRRAHRLLLAKRFLKREGILSTIDLEKGLPNQAWELRVAGLERRLSAIEWGAVLLHLIKHRGYLSKRKNESQTNNKELGALLSGVAQNHQLLQSDDYRTPAELALKKFAKEEGHIRNQRGAYTHTFNRLDLLAELNLLFAQQHQFGNPHCKEHIQQYMTELLMWQKPALSGEAILKMLGKCTHEKNEFKAAKHTYSAERFVWLTKLNNLRILEDGAERALNEEERQLLINHPYEKSKLTYAQVRKLLGLSEQAIFKHLRYSKENAESATFMELKAWHAIRKALENQGLKDTWQDLAKKPDLLDEIGTAFSLYKTDEDIQQYLTNKVPNSVINALLVSLNFDKFIELSLKSLRKILPLMEQGKRYDQACREIYGHHYGEANQKTSQLLPAIPAQEIRNPVVLRTLSQARKVINAIIRQYGSPARVHIETGRELGKSFKERREIQKQQEDNRTKRESAVQKFKELFSDFSSEPKSKDILKFRLYEQQHGKCLYSGKEINIHRLNEKGYVEIDHALPFSRTWDDSFNNKVLVLASENQNKGNQTPYEWLQGKINSERWKNFVALVLGSQCSAAKKQRLLTQVIDDNKFIDRNLNDTRYIARFLSNYIQENLLLVGKNKKNVFTPNGQITALLRSRWGLIKARENNNRHHALDAIVVACATPSMQQKITRFIRFKEVHPYKIENRYEMVDQESGEIISPHFPEPWAYFRQEVNIRVFDNHPDTVLKEMLPDRPQANHQFVQPLFVSRAPTRKMSGQGHMETIKSAKRLAEGISVLRIPLTQLKPNLLENMVNKEREPALYAGLKARLAEFNQDPAKAFATPFYKQGGQQVKAIRVEQVQKSGVLVRENNGVADNASIVRTDVFIKNNKFFLVPIYTWQVAKGILPNKAIVAHKNEDEWEEMDEGAKFKFSLFPNDLVELKTKKEYFFGYYIGLDRATGNISLKEHDGEISKGKDGVYRVGVKLALSFEKYQVDELGKNRQICRPQQRQPVR(SEQ ID NO:162)
在一些实施方案中，所述Cas9蛋白可以是新凶手弗朗西丝菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MNFKILPIAIDLGVKNTGVFSAFYQKGTSLERLDNKNGKVYELSKDSYTLLMNNRTARRHQRRGIDRKQLVKRLFKLIWTEQLNLEWDKDTQQAISFLFNRRGFSFITDGYSPEYLNIVPEQVKAILMDIFDDYNGEDDLDSYLKLATEQESKISEIYNKLMQKILEFKLMKLCTDIKDDKVSTKTLKEITSYEFELLADYLANYSESLKTQKFSYTDKQGNLKELSYYHHDKYNIQEFLKRHATINDRILDTLLTDDLDIWNFNFEKFDFDKNEEKLQNQEDKDHIQAHLHHFVFAVNKIKSEMASGGRHRSQYFQEITNVLDENNHQEGYLKNFCENLHNKKYSNLSVKNLVNLIGNLSNLELKPLRKYFNDKIHAKADHWDEQKFTETYCHWILGEWRVGVKDQDKKDGAKYSYKDLCNELKQKVTKAGLVDFLLELDPCRTIPPYLDNNNRKPPKCQSLILNPKFLDNQYPNWQQYLQELKKLQSIQNYLDSFETDLKVLKSSKDQPYFVEYKSSNQQIASGQRDYKDLDARILQFIFDRVKASDELLLNEIYFQAKKLKQKASSELEKLESSKKLDEVIANSQLSQILKSQHTNGIFEQGTFLHLVCKYYKQRQRARDSRLYIMPEYRYDKKLHKYNNTGRFDDDNQLLTYCNHKPRQKRYQLLNDLAGVLQVSPNFLKDKIGSDDDLFISKWLVEHIRGFKKACEDSLKIQKDNRGLLNHKINIARNTKGKCEKEIFNLICKIEGSEDKKGNYKHGLAYELGVLLFGEPNEASKPEFDRKIKKFNSIYSFAQIQQIAFAERKGNANTCAVCSADNAHRMQQIKITEPVEDNKDKIILSAKAQRLPAIPTRIVDGAVKKMATILAKNIVDDNWQNIKQVLSAKHQLHIPIITESNAFEFEPALADVKGKSLKDRRKKALERISPENIFKDKNNRIKEFAKGISAYSGANLTDGDFDGAKEELDHIIPRSHKKYGTLNDEANLICVTRGDNKNKGNRIFCLRDLADNYKLKQFETTDDLEIEKKIADTIWDANKKDFKFGNYRSFINLTPQEQKAFRHALFLADENPIKQAVIRAINNRNRTFVNGTQRYFAEVLANNIYLRAKKENLNTDKISFDYFGIPTIGNGRGIAEIRQLYEKVDSDIQAYAKGDKPQASYSHLIDAMLAFCIAADEHRNDGSIGLEIDKNYSLYPLDKNTGEVFTKDIFSQIKITDNEFSDKKLVRKKAIEGFNTHRQMTRDGIYAENYLPILIHKELNEVRKGYTWKNSEEIKIFKGKKYDIQQLNNLVYCLKFVDKPISIDIQISTLEELRNILTTNNIAATAEYYYINLKTQKLHEYYIENYNTALGYKKYSKEMEFLRSLAYRSERVKIKSIDDVKQVLDKDSNFIIGKITLPFKKEWQRLYREWQNTTIKDDYEFLKSFFNVKSITKLHKKVRKDFSLPISTNEGKFLVKRKTWDNNFIYQILNDSDSRADGTKPFIPAFDISKNEIVEAIIDSFTSKNIFWLPKNIELQKVDNKNIFAIDTSKWFEVETPSDLRDIGIATIQYKIDNNSRPKVRVKLDYVIDDDSKINYFMNHSLLKSRYPDKVLEILKQSTIIEFESSGFNKTIKEMLGMKLAGIYNETSNN(SEQ ID NO:163)
在一些实施方案中，所述Cas9蛋白可以是布氏乳杆菌(Lactobacillus buchneri)Cas9，并且可以包含以下氨基酸序列或由其组成：
MKVNNYHIGLDIGTSSIGWVAIGKDGKPLRVKGKTAIGARLFQEGNPAADRRMFRTTRRRLSRRKWRLKLLEEIFDPYITPVDSTFFARLKQSNLSPKDSRKEFKGSMLFPDLTDMQYHKNYPTIYHLRHALMTQDKKFDIRMVYLAIHHIVKYRGNFLNSTPVDSFKASKVDFVDQFKKLNELYAAINPEESFKINLANSEDIGHQFLDPSIRKFDKKKQIPKIVPVMMNDKVTDRLNGKIASEIIHAILGYKAKLDVVLQCTPVDSKPWALKFDDEDIDAKLEKILPEMDENQQSIVAILQNLYSQVTLNQIVPNGMSLSESMIEKYNDHHDHLKLYKKLIDQLADPKKKAVLKKAYSQYVGDDGKVIEQAEFWSSVKKNLDDSELSKQIMDLIDAEKFMPKQRTSQNGVIPHQLHQRELDEIIEHQSKYYPWLVEINPNKHDLHLAKYKIEQLVAFRVPYYVGPMITPKDQAESAETVFSWMERKGTETGQITPWNFDEKVDRKASANRFIKRMTTKDTYLIGEDVLPDESLLYEKFKVLNELNMVRVNGKLLKVADKQAIFQDLFENYKHVSVKKLQNYIKAKTGLPSDPEISGLSDPEHFNNSLGTYNDFKKLFGSKVDEPDLQDDFEKIVEWSTVFEDKKILREKLNEITWLSDQQKDVLESSRYQGWGRLSKKLLTGIVNDQGERIIDKLWNTNKNFMQIQSDDDFAKRIHEANADQMQAVDVEDVLADAYTSPQNKKAIRQVVKVVDDIQKAMGGVAPKYISIEFTRSEDRNPRRTISRQRQLENTLKDTAKSLAKSINPELLSELDNAAKSKKGLTDRLYLYFTQLGKDIYTGEPINIDELNKYDIDHILPQAFIKDNSLDNRVLVLTAVNNGKSDNVPLRMFGAKMGHFWKQLAEAGLISKRKLKNLQTDPDTISKYAMHGFIRRQLVETSQVIKLVANILGDKYRNDDTKIIEITARMNHQMRDEFGFIKNREINDYHHAFDAYLTAFLGRYLYHRYIKLRPYFVYGDFKKFREDKVTMRNFNFLHDLTDDTQEKIADAETGEVIWDRENSIQQLKDVYHYKFMLISHEVYTLRGAMFNQTVYPASDAGKRKLIPVKADRPVNVYGGYSGSADAYMAIVRIHNKKGDKYRVVGVPMRALDRLDAAKNVSDADFDRALKDVLAPQLTKTKKSRKTGEITQVIEDFEIVLGKVMYRQLMIDGDKKFMLGSSTYQYNAKQLVLSDQSVKTLASKGRLDPLQESMDYNNVYTEILDKVNQYFSLYDMNKFRHKLNLGFSKFISFPNHNVLDGNTKVSSGKREILQEILNGLHANPTFGNLKDVGITTPFGQLQQPNGILLSDETKIRYQSPTGLFERTVSLKDL(SEQ ID NO:164)
在一些实施方案中，所述Cas9蛋白可以是无害李斯特菌(Listeria innocua)Cas9，并且可以包含以下氨基酸序列或由其组成：
MKKPYTIGLDIGTNSVGWAVLTDQYDLVKRKMKIAGDSEKKQIKKNFWGVRLFDEGQTAADRRMARTARRRIERRRNRISYLQGIFAEEMSKTDANFFCRLSDSFYVDNEKRNSRHPFFATIEEEVEYHKNYPTIYHLREELVNSSEKADLRLVYLALAHIIKYRGNFLIEGALDTQNTSVDGIYKQFIQTYNQVFASGIEDGSLKKLEDNKDVAKILVEKVTRKEKLERILKLYPGEKSAGMFAQFISLIVGSKGNFQKPFDLIEKSDIECAKDSYEEDLESLLALIGDEYAELFVAAKNAYSAVVLSSIITVAETETNAKLSASMIERFDTHEEDLGELKAFIKLHLPKHYEEIFSNTEKHGYAGYIDGKTKQADFYKYMKMTLENIEGADYFIAKIEKENFLRKQRTFDNGAIPHQLHLEELEAILHQQAKYYPFLKENYDKIKSLVTFRIPYFVGPLANGQSEFAWLTRKADGEIRPWNIEEKVDFGKSAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYLVYNELTKVRYINDQGKTSYFSGQEKEQIFNDLFKQKRKVKKKDLELFLRNMSHVESPTIEGLEDSFNSSYSTYHDLLKVGIKQEILDNPVNTEMLENIVKILTVFEDKRMIKEQLQQFSDVLDGVVLKKLERRHYTGWGRLSAKLLMGIRDKQSHLTILDYLMNDDGLNRNLMQLINDSNLSFKSIIEKEQVTTADKDIQSIVADLAGSPAIKKGILQSLKIVDELVSVMGYPPQTIVVEMARENQTTGKGKNNSRPRYKSLEKAIKEFGSQILKEHPTDNQELRNNRLYLYYLQNGKDMYTGQDLDIHNLSNYDIDHIVPQSFITDNSIDNLVLTSSAGNREKGDDVPPLEIVRKRKVFWEKLYQGNLMSKRKFDYLTKAERGGLTEADKARFIHRQLVETRQITKNVANILHQRFNYEKDDHGNTMKQVRIVTLKSALVSQFRKQFQLYKVRDVNDYHHAHDAYLNGVVANTLLKVYPQLEPEFVYGDYHQFDWFKANKATAKKQFYTNIMLFFAQKDRIIDENGEILWDKKYLDTVKKVMSYRQMNIVKKTEIQKGEFSKATIKPKGNSSKLIPRKTNWDPMKYGGLDSPNMAYAVVIEYAKGKNKLVFEKKIIRVTIMERKAFEKDEKAFLEEQGYRQPKVLAKLPKYTLYECEEGRRRMLASANEAQKGNQQVLPNHLVTLLHHAANCEVSDGKSLDYIESNREMFAELLAHVSEFAKRYTLAEANLNKINQLFEQNKEGDIKAIAQSFVDLMAFNAMGAPASFKFFETTIERKRYNNLKELLNSTIIYQSITGLYESRKRLDD(SEQ ID NO:165)
在一些实施方案中，所述Cas9蛋白可以是嗜肺军团菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MESSQILSPIGIDLGGKFTGVCLSHLEAFAELPNHANTKYSVILIDHNNFQLSQAQRRATRHRVRNKKRNQFVKRVALQLFQHILSRDLNAKEETALCHYLNNRGYTYVDTDLDEYIKDETTINLLKELLPSESEHNFIDWFLQKMQSSEFRKILVSKVEEKKDDKELKNAVKNIKNFITGFEKNSVEGHRHRKVYFENIKSDITKDNQLDSIKKKIPSVCLSNLLGHLSNLQWKNLHRYLAKNPKQFDEQTFGNEFLRMLKNFRHLKGSQESLAVRNLIQQLEQSQDYISILEKTPPEITIPPYEARTNTGMEKDQSLLLNPEKLNNLYPNWRNLIPGIIDAHPFLEKDLEHTKLRDRKRIISPSKQDEKRDSYILQRYLDLNKKIDKFKIKKQLSFLGQGKQLPANLIETQKEMETHFNSSLVSVLIQIASAYNKEREDAAQGIWFDNAFSLCELSNINPPRKQKILPLLVGAILSEDFINNKDKWAKFKIFWNTHKIGRTSLKSKCKEIEEARKNSGNAFKIDYEEALNHPEHSNNKALIKIIQTIPDIIQAIQSHLGHNDSQALIYHNPFSLSQLYTILETKRDGFHKNCVAVTCENYWRSQKTEIDPEISYASRLPADSVRPFDGVLARMMQRLAYEIAMAKWEQIKHIPDNSSLLIPIYLEQNRFEFEESFKKIKGSSSDKTLEQAIEKQNIQWEEKFQRIINASMNICPYKGASIGGQGEIDHIYPRSLSKKHFGVIFNSEVNLIYCSSQGNREKKEEHYLLEHLSPLYLKHQFGTDNVSDIKNFISQNVANIKKYISFHLLTPEQQKAARHALFLDYDDEAFKTITKFLMSQQKARVNGTQKFLGKQIMEFLSTLADSKQLQLEFSIKQITAEEVHDHRELLSKQEPKLVKSRQQSFPSHAIDATLTMSIGLKEFPQFSQELDNSWFINHLMPDEVHLNPVRSKEKYNKPNISSTPLFKDSLYAERFIPVWVKGETFAIGFSEKDLFEIKPSNKEKLFTLLKTYSTKNPGESLQELQAKSKAKWLYFPINKTLALEFLHHYFHKEIVTPDDTTVCHFINSLRYYTKKESITVKILKEPMPVLSVKFESSKKNVLGSFKHTIALPATKDWERLFNHPNFLALKANPAPNPKEFNEFIRKYFLSDNNPNSDIPNNGHNIKPQKHKAVRKVFSLPVIPGNAGTMMRIRRKDNKGQPLYQLQTIDDTPSMGIQINEDRLVKQEVLMDAYKTRNLSTIDGINNSEGQAYATFDNWLTLPVSTFKPEIIKLEMKPHSKTRRYIRITQSLADFIKTIDEALMIKPSDSIDDPLNMPNEIVCKNKLFGNELKPRDGKMKIVSTGKIVTYEFESDSTPQWIQTLYVTQLKKQP(SEQ ID NO:166)
在一些实施方案中，所述Cas9蛋白可以是嗜乳糖奈瑟球菌(N.lactamica)Cas9，并且可以包含以下氨基酸序列或由其组成：MAAFKPNPMNYILGLDIGIASVGWAMVEVDEEENPIRLIDLGVRVFERAEVPKTGDSLAMARRLARSVRRLTRRRAHRLLRARRLLKREGVLQDADFDENGLVKSLPNTPWQLRAAALDRKLTCLEWSAVLLHLVKHRGYLSQRKNEGETADKELGALLKGVADNAHALQTGDFRTPAELALNKFEKESGHIRNQRGDYSHTFSRKDLQAELNLLFEKQKEFGNPHVSDGLKEDIETLLMAQRPALSGDAVQKMLGHCTFEPAEPKAAKNTYTAERFIWLTKLNNLRILEQGSERPLTDTERATLMDEPYRKSKLTYAQARKLLGLEDTAFFKGLRYGKDNAEASTLMEMKAYHAISRALEKEGLKDKKSPLNLSTELQDEIGTAFSLFKTDKDITGRLKDRVQPEILEALLKHISFDKFVQISLKALRRIVPLMEQGKRYDEACAEIYGDHYCKKNAEEKIYLPPIPADEIRNPVVLRALSQARKVINCVVRRYGSPARIHIETAREVGKSFKDRKEIEKRQEENRKDREKAAAKFREYFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLVRLNEKGYVEIDHALPFSRTWDDSFNNKVLVLGSENQNKGNQTPYEYFNGKDNSREWQEFKARVETSRFPRSKKQRILLQKFDEEGFKERNLNDTRYVNRFLCQFVADHILLTGKGKRRVFASNGQITNLLRGFWGLRKVRTENDRHHALDAVVVACSTVAMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQKAHFPQPWEFFAQEVMIRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHEYVTPLFVSRAPNRKMSGQGHMETVKSAKRLDEGISVLRVPLTQLKLKGLEKMVNREREPKLYDALKAQLETHKDDPAKAFAEPFYKYDKAGSRTQQVKAVRIEQVQKTGVWVRNHNGIADNATMVRVDVFEKGGKYYLVPIYSWQVAKGILPDRAVVAFKDEEDWTVMDDSFEFRFVLYANDLIKLTAKKNEFLGYFVSLNRATGAIDIRTHDTDSTKGKNGIFQSVGVKTALSFQKNQIDELGKEIRPCRLKKRPPVR(SEQ ID NO:167)
在一些实施方案中，所述Cas9蛋白可以是脑膜炎奈瑟球菌Cas9，并且可以包含以下氨基酸序列或由其组成：
MAAFKPNPINYILGLDIGIASVGWAMVEIDEDENPICLIDLGVRVFERAEVPKTGDSLAMARRLARSVRRLTRRRAHRLLRARRLLKREGVLQAADFDENGLIKSLPNTPWQLRAAALDRKLTPLEWSAVLLHLIKHRGYLSQRKNEGETADKELGALLKGVADNAHALQTGDFRTPAELALNKFEKESGHIRNQRGDYSHTFSRKDLQAELILLFEKQKEFGNPHVSGGLKEGIETLLMTQRPALSGDAVQKMLGHCTFEPAEPKAAKNTYTAERFIWLTKLNNLRILEQGSERPLTDTERATLMDEPYRKSKLTYAQARKLLGLEDTAFFKGLRYGKDNAEASTLMEMKAYHAISRALEKEGLKDKKSPLNLSPELQDEIGTAFSLFKTDEDITGRLKDRIQPEILEALLKHISFDKFVQISLKALRRIVPLMEQGKRYDEACAEIYGDHYGKKNTEEKIYLPPIPADEIRNPVVLRALSQARKVINGVVRRYGSPARIHIETAREVGKSFKDRKEIEKRQEENRKDREKAAAKFREYFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLGRLNEKGYVEIDHALPFSRTWDDSFNNKVLVLGSENQNKGNQTPYEYFNGKDNSREWQEFKARVETSRFPRSKKQRILLQKFDEDGFKERNLNDTRYVNRFLCQFVADRMRLTGKGKKRVFASNGQITNLLRGFWGLRKVRAENDRHHALDAVVVACSTVAMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQKTHFPQPWEFFAQEVMIRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHEYVTPLFVSRAPNRKMSGQGHMETVKSAKRLDEGVSVLRVPLTQLKLKDLEKMVNREREPKLYEALKARLEAHKDDPAKAFAEPFYKYDKAGNRTQQVKAVRVEQVQKTGVWVRNHNGIADNATMVRVDVFEKGDKYYLVPIYSWQVAKGILPDRAVVQGKDEEDWQLIDDSFNFKFSLHPNDLVEVITKKARMFGYFASCHRGTGNINIRIHDLDHKIGKNGILEGIGVKTALSFQKYQIDELGKEIRPCRLKKRPPVR(SEQ ID NO:168)
在一些实施方案中，所述Cas9蛋白可以是长双歧杆菌(B.longum)Cas9，并且可以包含以下氨基酸序列或由其组成：MLSRQLLGASHLARPVSYSYNVQDNDVHCSYGERCFMRGKRYRIGIDVGLNSVGLAAVEVSDENSPVRLLNAQSVIHDGGVDPQKNKEAITRKNMSGVARRTRRMRRRKRERLHKLDMLLGKFGYPVIEPESLDKPFEEWHVRAELATRYIEDDELRRESISIALRHMARHRGWRNPYRQVDSLISDNPYSKQYGELKEKAKAYNDDATAAEEESTPAQLVVAMLDAGYAEAPRLRWRTGSKKPDAEGYLPVRLMQEDNANELKQIFRVQRVPADEWKPLFRSVFYAVSPKGSAEQRVGQDPLAPEQARALKASLAFQEYRIANVITNLRIKDASAELRKLTVDEKQSIYDQLVSPSSEDITWSDLCDFLGFKRSQLKGVGSLTEDGEERISSRPPRLTSVQRIYESDNKIRKPLVAWWKSASDNEHEAMIRLLSNTVDIDKVREDVAYASAIEFIDGLDDDALTKLDSVDLPSGRAAYSVETLQKLTRQMLTTDDDLHEARKTLFNVTDSWRPPADPIGEPLGNPSVDRVLKNVNRYLMNCQQRWGNPVSVNIEHVRSSFSSVAFARKDKREYEKNNEKRSIFRSSLSEQLRADEQMEKVRESDLRRLEAIQRQNGQCLYCGRTITFRTCEMDHIVPRKGVGSTNTRTNFAAVCAECNRMKSNTPFAIWARSEDAQTRGVSLAEAKKRVTMFTFNPKSYAPREVKAFKQAVIARLQQTEDDAAIDNRSIESVAWMADELHRRIDWYFNAKQYVNSASIDDAEAETMKTTVSVFQGRVTASARRAAGIEGKIHFIGQQSKTRLDRRHHAVDASVIAMMNTAAAQTLMERESLRESQRLIGLMPGERSWKEYPYEGTSRYESFHLWLDNMDVLLELLNDALDNDRIAVMQSQRYVLGNSIAHDATIHPLEKVPLGSAMSADLIRRASTPALWCALTRLPDYDEKEGLPEDSHREIRVHDTRYSADDEMGFFASQAAQIAVQEGSADIGSAIHHARVYRCWKTNAKGVRKYFYGMIRVFQTDLLRACHDDLFTVPLPPQSISMRYGEPRVVQALQSGNAQYLGSLVVGDEIEMDFSSLDVDGQIGEYLQFFSQFSGGNLAWKHWVVDGFFNQTQLRIRPRYLAAEGLAKAFSDDVVPDGVQKIVTKQGWLPPVNTASKTAVRIVRRNAFGEPRLSSAHHMPCSWQWRHE(SEQ ID NO:169)
在一些实施方案中，所述Cas9蛋白可以是嗜粘蛋白艾克曼菌(A.muciniphila)Cas9，并且可以包含以下氨基酸序列或由其组成：
MSRSLTFSFDIGYASIGWAVIASASHDDADPSVCGCGTVLFPKDDCQAFKRREYRRLRRNIRSRRVRIERIGRLLVQAQIITPEMKETSGHPAPFYLASEALKGHRTLAPIELWHVLRWYAHNRGYDNNASWSNSLSEDGGNGEDTERVKHAQDLMDKHGTATMAETICRELKLEEGKADAPMEVSTPAYKNLNTAFPRLIVEKEVRRILELSAPLIPGLTAEIIELIAQHHPLTTEQRGVLLQHGIKLARRYRGSLLFGQLIPRFDNRIISRCPVTWAQVYEAELKKGNSEQSARERAEKLSKVPTANCPEFYEYRMARILCNIRADGEPLSAEIRRELMNQARQEGKLTKASLEKAISSRLGKETETNVSNYFTLHPDSEEALYLNPAVEVLQRSGIGQILSPSVYRIAANRLRRGKSVTPNYLLNLLKSRGESGEALEKKIEKESKKKEADYADTPLKPKYATGRAPYARTVLKKVVEEILDGEDPTRPARGEAHPDGELKAHDGCLYCLLDTDSSVNQHQKERRLDTMTNNHLVRHRMLILDRLLKDLIQDFADGQKDRISRVCVEVGKELTTFSAMDSKKIQRELTLRQKSHTDAVNRLKRKLPGKALSANLIRKCRIAMDMNWTCPFTGATYGDHELENLELEHIVPHSFRQSNALSSLVLTWPGVNRMKGQRTGYDFVEQEQENPVPDKPNLHICSLNNYRELVEKLDDKKGHEDDRRRKKKRKALLMVRGLSHKHQSQNHEAMKEIGMTEGMMTQSSHLMKLACKSIKTSLPDAHIDMIPGAVTAEVRKAWDVFGVFKELCPEAADPDSGKILKENLRSLTHLHHALDACVLGLIPYIIPAHHNGLLRRVLAMRRIPEKLIPQVRPVANQRHYVLNDDGRMMLRDLSASLKENIREQLMEQRVIQHVPADMGGALLKETMQRVLSVDGSGEDAMVSLSKKKDGKKEKNQVKASKLVGVFPEGPSKLKALKAAIEIDGNYGVALDPKPVVIRHIKVFKRIMALKEQNGGKPVRILKKGMLIHLTSSKDPKHAGVWRIESIQDSKGGVKLDLQRAHCAVPKNKTHECNWREVDLISLLKKYQMKRYPTSYTGTPR(SEQ ID NO:170)
在一些实施方案中，所述Cas9蛋白可以是兰氏臭杆菌(O.laneus)Cas9，并且可以包含以下氨基酸序列或由其组成：
METTLGIDLGTNSIGLALVDQEEHQILYSGVRIFPEGINKDTIGLGEKEESRNATRRAKRQMRRQYFRKKLRKAKLLELLIAYDMCPLKPEDVRRWKNWDKQQKSTVRQFPDTPAFREWLKQNPYELRKQAVTEDVTRPELGRILYQMIQRRGFLSSRKGKEEGKIFTGKDRMVGIDETRKNLQKQTLGAYLYDIAPKNGEKYRFRTERVRARYTLRDMYIREFEIIWQRQAGHLGLAHEQATRKKNIFLEGSATNVRNSKLITHLQAKYGRGHVLIEDTRITVTFQLPLKEVLGGKIEIEEEQLKFKSNESVLFWQRPLRSQKSLLSKCVFEGRNFYDPVHQKWIIAGPTPAPLSHPEFEEFRAYQFINNIIYGKNEHLTAIQREAVFELMCTESKDFNFEKIPKHLKLFEKFNFDDTTKVPACTTISQLRKLFPHPVWEEKREEIWHCFYFYDDNTLLFEKLQKDYALQTNDLEKIKKIRLSESYGNVSLKAIRRINPYLKKGYAYSTAVLLGGIRNSFGKRFEYFKEYEPEIEKAVCRILKEKNAEGEVIRKIKDYLVHNRFGFAKNDRAFQKLYHHSQAITTQAQKERLPETGNLRNPIVQQGLNELRRTVNKLLATCREKYGPSFKFDHIHVEMGRELRSSKTEREKQSRQIRENEKKNEAAKVKLAEYGLKAYRDNIQKYLLYKEIEEKGGTVCCPYTGKTLNISHTLGSDNSVQIEHIIPYSISLDDSLANKTLCDATFNREKGELTPYDFYQKDPSPEKWGASSWEEIEDRAFRLLPYAKAQRFIRRKPQESNEFISRQLNDTRYISKKAVEYLSAICSDVKAFPGQLTAELRHLWGLNNILQSAPDITFPLPVSATENHREYYVITNEQNEVIRLFPKQGETPRTEKGELLLTGEVERKVFRCKGMQEFQTDVSDGKYWRRIKLSSSVTWSPLFAPKPISADGQIVLKGRIEKGVFVCNQLKQKLKTGLPDGSYWISLPVISQTFKEGESVNNSKLTSQQVQLFGRVREGIFRCHNYQCPASGADGNFWCTLDTDTAQPAFTPIKNAPPGVGGGQIILTGDVDDKGIFHADDDLHYELPASLPKGKYYGIFTVESCDPTLIPIELSAPKTSKGENLIEGNIWVDEHTGEVRFDPKKNREDQRHHAIDAIVIALSSQSLFQRLSTYNARRENKKRGLDSTEHFPSPWPGFAQDVRQSVVPLLVSYKQNPKTLCKISKTLYKDGKKIHSCGNAVRGQLHKETVYGQRTAPGATEKSYHIRKDIRELKTSKHIGKVVDITIRQMLLKHLQENYHIDITQEFNIPSNAFFKEGVYRIFLPNKHGEPVPIKKIRMKEELGNAERLKDNINQYVNPRNNHHVMIYQDADGNLKEEIVSFWSVIERQNQGQPIYQLPREGRNIVSILQINDTFLIGLKEEEPEVYRNDLSTLSKHLYRVQKLSGMYYTFRHHLASTLNNEREEFRIQSLEAWKRANPVKVQIDEIGRITFLNGPLC(SEQ ID NO:171)。
在本公开文本的组合物的一些实施方案中，编码第一RNA结合蛋白的序列包含从CRISPR Cas蛋白或其部分分离或衍生的序列。在一些实施方案中，所述CRISPR Cas蛋白包含V型CRISPR Cas蛋白。在一些实施方案中，所述V型CRISPR Cas蛋白包含Cpf1蛋白。本公开文本的示例性Cpf1蛋白可以从任何物种分离或衍生，所述物种包括但不限于细菌或古菌。本公开文本的示例性Cpf1蛋白可以从任何物种分离或衍生，所述物种包括但不限于土拉热弗朗西丝菌新凶手亚种、氨基酸球菌属物种(Acidaminococcus sp.)BV3L6和毛螺科细菌物种(Lachnospiraceae bacterium sp.)ND2006。本公开文本的示例性Cpf1蛋白可以是核酸酶失活的。
本公开文本的示例性野生型土拉热弗朗西丝菌新凶手亚种Cpf1(FnCpf1)蛋白可以包含以下氨基酸序列或由其组成：
Figure BDA0002919433300000431
本公开文本的示例性野生型毛螺科细菌物种ND2006 Cpf1(LbCpf1)蛋白可以包含以下氨基酸序列或由其组成：
Figure BDA0002919433300000432
Figure BDA0002919433300000441
本公开文本的示例性野生型氨基酸球菌属物种BV3L6 Cpf1(AsCpf1)蛋白可以包含以下氨基酸序列或由其组成：
Figure BDA0002919433300000442
Figure BDA0002919433300000451
在本公开文本的组合物的一些实施方案中，编码第一RNA结合蛋白的序列包含从CRISPR Cas蛋白分离或衍生的序列。在一些实施方案中，所述CRISPR Cas蛋白包含VI型CRISPR Cas蛋白或其部分。在一些实施方案中，所述VI型CRISPR Cas蛋白包含Cas13蛋白或其部分。本公开文本的示例性Cas13蛋白可以从任何物种分离或衍生，所述物种包括但不限于细菌或古菌。本公开文本的示例性Cas13蛋白可以从任何物种分离或衍生，所述物种包括但不限于韦德纤毛菌(Leptotrichia wadei)、西尔李斯特菌血清变型(Listeriaseeligeri serovar)1/2b(菌株ATCC 35967/DSM 20751/CIP 100100/SLCC 3954)、毛螺科细菌、嗜氨基梭菌(Clostridium aminophilum)DSM 10710、鸡肉杆菌(Carnobacteriumgallinarum)DSM 4847、产丙酸沼杆菌(Paludibacter propionicigenes)WB4、韦氏李斯特菌(Listeria weihenstephanensis)FSL R9-0317、韦氏李斯特菌FSL R9-0317、细菌FSLM6-0635(纽约李斯特菌(Listeria newyorkensis))、韦德纤毛菌F0279、荚膜红细菌(Rhodobacter capsulatus)SB 1003、荚膜红细菌R121、荚膜红细菌DE442和溃疡棒状杆菌(Corynebacterium ulcerans)。本公开文本的示例性Cas13蛋白可以是DNA核酸酶失活的。本公开文本的示例性Cas13蛋白包括但不限于Cas13a、Cas13b、Cas13c、Cas13d及其直系同源物。本公开文本的示例性Cas13b蛋白包括但不限于亚型1和2，在本文中分别称为Csx27和Csx28。
示例性Cas13a蛋白包括但不限于：
Figure BDA0002919433300000452
Figure BDA0002919433300000461
Figure BDA0002919433300000471
本公开文本的示例性野生型Cas13a蛋白可以包含以下氨基酸序列或由其组成：
Figure BDA0002919433300000472
Figure BDA0002919433300000481
示例性Cas13b蛋白包括但不限于：
Figure BDA0002919433300000482
Figure BDA0002919433300000491
Figure BDA0002919433300000501
Figure BDA0002919433300000511
本公开文本的示例性野生型动物溃疡伯格菌ATCC 43767 Cas13b(BzCas13b)蛋白可以包含以下氨基酸序列或由其组成：
Figure BDA0002919433300000512
Figure BDA0002919433300000521
在本公开文本的组合物的一些实施方案中，编码第一RNA结合蛋白的序列包含从CasRX/Cas13d蛋白分离或衍生的序列。CasRX/Cas13d是VI-D型CRISPR-Cas系统的效应子。在一些实施方案中，所述CasRX/Cas13d蛋白是可以切割或结合RNA的RNA指导的RNA内切核酸酶。在一些实施方案中，所述CasRX/Cas13d蛋白可以包括一个或多个高等真核生物和原核生物核苷酸结合(HEPN)结构域。在一些实施方案中，所述CasRX/Cas13d蛋白可以包括野生型或突变的HEPN结构域。在一些实施方案中，所述CasRX/Cas13d蛋白包括无法切割RNA但可以加工指导RNA的突变的HEPN结构域。在一些实施方案中，所述CasRX/Cas13d蛋白不需要原间隔子侧翼序列。关于CasRX/Cas13d蛋白的其他例子和序列还参见WO公开号WO 2019/040664和US 2019/0062724，将其通过引用以其整体并入本文，在没有限制的情况下，具体参考
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d肠道_宏基因组_重叠群6049000251(CasRX/Cas13d Gut_metagenome_contig6049000251)：
Figure BDA0002919433300000522
(SEQ ID NO:54)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d肠道_宏基因组_重叠群546000275：
Figure BDA0002919433300000531
(SEQ ID NO:57)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群4114000374：
Figure BDA0002919433300000532
(SEQ ID NO:61)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群721000619：
Figure BDA0002919433300000533
(SEQ ID NO:67)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群2002000411：
Figure BDA0002919433300000534
(SEQ ID NO:69)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群13552000311：
Figure BDA0002919433300000541
(SEQ ID NO:71)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群10037000527：
Figure BDA0002919433300000542
(SEQ ID NO:72)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群238000329：
Figure BDA0002919433300000543
(SEQ ID NO:73)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群2643000492：
Figure BDA0002919433300000544
Figure BDA0002919433300000551
(SEQ ID NO:84)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群874000057：
Figure BDA0002919433300000552
(SEQ ID NO:85)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群4781000489：
Figure BDA0002919433300000553
(SEQ ID NO:86)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群12144000352：
Figure BDA0002919433300000554
(SEQ ID NO:87)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群5590000448：
Figure BDA0002919433300000555
Figure BDA0002919433300000561
(SEQ ID NO:88)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群525000349：
Figure BDA0002919433300000562
(SEQ ID NO:89)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群7229000302：
Figure BDA0002919433300000563
(SEQ ID NO:90)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群3227000343：
Figure BDA0002919433300000564
(SEQ ID NO:91)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_重叠群7030000469：
Figure BDA0002919433300000565
(SEQ ID NO:92)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d肠道_宏基因组_P17E0k2120140920，c87000043：
Figure BDA0002919433300000571
(SEQ ID NO:93)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群emb|OBVH01003037.1，人肠宏基因组序列(也发现于WGS重叠群emb|OBXZ01000094.1|和emb|OBJF01000033.1|)：
Figure BDA0002919433300000572
(SEQ ID NO:94)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群tpg|DJXD01000002.1|(未培育的瘤胃球菌属(Ruminococcus)联合体，UBA7013，来自绵羊肠道宏基因组)：
Figure BDA0002919433300000573
Figure BDA0002919433300000581
(SEQ ID NO:95)。
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群tpg|DJXD01000002.1|(未培育的瘤胃球菌属联合体，UBA7013，来自绵羊肠道宏基因组)(SEQ ID NO:95)的示例性同向重复序列包含以下核酸序列或由其组成：
CasRX/Cas13d DR：
Figure BDA0002919433300000582
(SEQ ID NO:96)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群OGZC01000639.1(人肠道宏基因组联合体)：
Figure BDA0002919433300000583
Figure BDA0002919433300000591
(SEQ ID NO:97)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群emb|OHBM01000764.1(人肠道宏基因组联合体)：
Figure BDA0002919433300000592
Figure BDA0002919433300000601
(SEQ ID NO:98)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群emb|OHCP01000044.1(人肠道宏基因组联合体)：
Figure BDA0002919433300000602
(SEQ ID NO:99)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群emb|OGDF01008514.1|(人肠道宏基因组联合体)：
Figure BDA0002919433300000603
Figure BDA0002919433300000611
(SEQ ID NO:100)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群emb|OGPN01002610.1(人肠道宏基因组联合体)：
Figure BDA0002919433300000612
Figure BDA0002919433300000621
(SEQ ID NO:101)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：来自重叠群emb|OBLI01020244和emb|OBLI01038679(来自猪肠道宏基因组)：
Figure BDA0002919433300000622
(SEQ ID NO:102)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群OIZX01000427.1：
Figure BDA0002919433300000623
Figure BDA0002919433300000631
(SEQ ID NO:103)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群OCTW011587266.1：
Figure BDA0002919433300000632
Figure BDA0002919433300000641
(SEQ ID NO:104)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群emb|OGNF01009141.1：
Figure BDA0002919433300000642
(SEQ ID NO:105)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群emb|OIEN01002196.1：
Figure BDA0002919433300000643
Figure BDA0002919433300000651
(SEQ ID NO:106)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群e-k87_11092736：
Figure BDA0002919433300000652
Figure BDA0002919433300000661
(SEQ ID NO:107)。
CasRX/Cas13d宏基因组命中(无蛋白质登录号)：重叠群e-k87_11092736(SEQ IDNO:107)的示例性同向重复序列包含以下核酸序列或由其组成：CasRX/Cas13d同向重复1：gtgagaagtc tccttatggg gagatgctac
(SEQ ID NO:108)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d Ga0129306_1000735：
Figure BDA0002919433300000662
(SEQ ID NO:109)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d Ga0129317_1008067：
Figure BDA0002919433300000671
(SEQ ID NO:110)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d Ga0224415_10048792：
Figure BDA0002919433300000672
Figure BDA0002919433300000681
(SEQ ID NO:111)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：
CasRX/Cas13d 160582958_基因49834：
Figure BDA0002919433300000682
(SEQ ID NO:112)。
CasRX/Cas13d蛋白的示例性同向重复序列可以包含以下序列或由其组成：
CasRX/Cas13d 160582958_基因49834(SEQ ID NO:112)包含以下核酸序列或由其组成：CasRX/Cas13d DR：
Figure BDA0002919433300000683
(SEQ ID NO:113)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d250twins_35838_GL0110300：
Figure BDA0002919433300000691
(SEQ ID NO:114)。
示例性CasRX/Cas13d蛋白可以包含以下序列或由其组成：CasRX/Cas13d250twins_36050_GL0158985：
Figure BDA0002919433300000692
Figure BDA0002919433300000701
(SEQ ID NO:115)。
Yan等人(2018)Mol Cell.70(2):327-339(doi:10.1016/j.molcel.2018.02.2018)和Konermann等人(2018)Cell 173(3):665-676(doi:10.1016/j.cell/2018.02.033)已经描述了CasRX/Cas13d蛋白，将所述两篇参考文献都通过引用以其整体并入本文。还参见WO公开号WO 2018/183703(CasM)和WO 2019/006471(Cas13d)，将其通过引用以其整体并入本文。
本公开文本的示例性野生型Cas13d蛋白可以包含以下氨基酸序列或由其组成：
Cas13d(生黄瘤胃球菌(Ruminococcus flavefaciens)XPD3002)序列：
Figure BDA0002919433300000702
Figure BDA0002919433300000711
本公开文本的示例性野生型Cas13d蛋白可以包含以下氨基酸序列或由其组成：
Cas13d(重叠群e-k87_11092736)：
Figure BDA0002919433300000712
Cas13d(重叠群e-k87_11092736)(SEQ ID NO:46)的示例性同向重复序列包含以下核酸序列或由其组成：Cas13d(重叠群e-k87_11092736)同向重复序列：GTGAGAAGTCTCCTTATGGGGAGATGCTAC(SEQID NO:47)。
本公开文本的示例性野生型Cas13d蛋白可以包含以下氨基酸序列或由其组成：
Cas13d(160582958_基因49834)：
Figure BDA0002919433300000713
Figure BDA0002919433300000721
Cas13d(160582958_基因49834)(SEQ ID NO:48)的示例性同向重复序列包含以下核酸序列或由其组成：
Cas13d(160582958_基因49834)同向重复序列：GAACTACACCCCTCTGTTCTTGTAGGGGTCTAACAC(SEQ ID NO:49)。
本公开文本的示例性野生型Cas13d蛋白可以包含以下氨基酸序列或由其组成：
Cas13d(重叠群tpg|DJXD01000002.1|；未培育的瘤胃球菌属联合体，UBA7013，来自绵羊肠道宏基因组)：
Figure BDA0002919433300000722
Figure BDA0002919433300000731
Cas13d(重叠群tpg|DJXD01000002.1|；未培育的瘤胃球菌属联合体，UBA7013，来自绵羊肠道宏基因组)(SEQ ID NO:50)的示例性同向重复序列包含以下核酸序列或由其组成：Cas13d(重叠群tpg|DJXD01000002.1|；未培育的瘤胃球菌属联合体，UBA7013，来自绵羊肠道宏基因组)同向重复序列：CAACTACAACCCCGTAAAAATACGGGGTTCTGAAAC(SEQ ID NO:51)。
gRNA靶序列
在本公开文本的组合物的一些实施方案中，RNA分子的靶序列包含对应于第一RNA结合蛋白和/或第二RNA结合蛋白的序列基序。
在本公开文本的组合物和方法的一些实施方案中，所述序列基序是疾病或障碍的标志。
本公开文本的序列基序可以从基因组序列中发现的外来或外源序列的序列分离或衍生，并且因此翻译为本公开文本的mRNA分子或在本公开文本的RNA序列中发现的外来或外源序列的序列。
本公开文本的序列基序可以包含内源序列中引起疾病或障碍的突变或由其组成。所述突变可以包含序列取代、倒位、缺失、插入、转座或其任何组合，或者由其组成。
本公开文本的序列基序可以包含重复的序列或由其组成。在一些实施方案中，所述重复的序列可能与微卫星不稳定性(MSI)相关。一个或多个基因座处的MSI是由于本公开文本的细胞的DNA错配修复机制受损所致。可以将DNA的超变序列转录为本公开文本的包含靶序列的mRNA，所述靶序列包含所述超变序列或由其组成。
本公开文本的序列基序可以包含生物标记或由其组成。所述生物标记可以指示患上疾病或障碍的风险。所述生物标记可以指示健康基因(低或无可确定的患上疾病或障碍的风险)。所述生物标记可以指示编辑的基因。示例性生物标记包括但不限于单核苷酸多态性(SNP)、序列变异或突变、表观遗传标记、剪接受体位点、外源序列、异源序列及其任何组合。
本公开文本的序列基序可以包含二级、三级或四级结构或由其组成。所述二级、三级或四级结构可以是内源的或天然存在的。所述二级、三级或四级结构可以是诱导的或非天然存在的。所述二级、三级或四级结构可以由内源、外源或异源序列编码。
在本公开文本的组合物和方法的一些实施方案中，RNA分子的靶序列包含在2个与100个之间的核苷酸或核酸碱基(包括端点)或由其组成。在一些实施方案中，RNA分子的所述靶序列包含在2个与50个之间的核苷酸或核酸碱基(包括端点)或由其组成。在一些实施方案中，RNA分子的所述靶序列包含在2个与20个之间的核苷酸或核酸碱基(包括端点)或由其组成。
在本公开文本的组合物和方法的一些实施方案中，RNA分子的靶序列是连续的。在一些实施方案中，RNA分子的所述靶序列是不连续的。例如，RNA分子的所述靶序列可以包含不连续的一个或多个核苷酸或核酸碱基或由其组成，因为一个或多个间断的核苷酸定位于所述靶序列的核苷酸之间。
在本公开文本的组合物和方法的一些实施方案中，RNA分子的靶序列是天然存在的。在一些实施方案中，RNA分子的所述靶序列是非天然存在的。示例性的非天然存在的靶序列可以包含序列变异或突变、嵌合序列、外源序列、异源序列、嵌合序列、重组序列、包含修饰的或合成的核苷酸的序列或其任何组合，或者由其组成。
在本公开文本的组合物和方法的一些实施方案中，RNA分子的靶序列与本公开文本的指导RNA结合。
在本公开文本的组合物和方法的一些实施方案中，RNA分子的靶序列与本公开文本的第一RNA结合蛋白结合。
在本公开文本的组合物和方法的一些实施方案中，RNA分子的靶序列与本公开文本的第二RNA结合蛋白结合。
RNA分子
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子包含靶序列。在一些实施方案中，本公开文本的RNA分子包含至少一个靶序列。在一些实施方案中，本公开文本的RNA分子包含一个或多个靶序列。在一些实施方案中，本公开文本的RNA分子包含两个或更多个靶序列。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子是天然存在的RNA分子。在一些实施方案中，本公开文本的RNA分子是非天然存在的分子。示例性的非天然存在的RNA分子可以包含序列变异或突变、嵌合序列、外源序列、异源序列、嵌合序列、重组序列、包含修饰的或合成的核苷酸的序列或其任何组合，或者由其组成。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子包含从病毒分离或衍生的序列或由其组成。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子包含从原核生物分离或衍生的序列或由其组成。在一些实施方案中，本公开文本的RNA分子包含从古菌的物种或菌株或者细菌的物种或菌株分离或衍生的序列或由其组成。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子包含从真核生物分离或衍生的序列或由其组成。在一些实施方案中，本公开文本的RNA分子包含从以下的物种分离或衍生的序列或由其组成：原生动物、寄生虫、原生生物、藻类、真菌、酵母、变形虫、蠕虫、微生物、无脊椎动物、脊椎动物、昆虫、啮齿类动物、小鼠、大鼠、哺乳动物或灵长类动物。在一些实施方案中，本公开文本的RNA分子包含从人分离或衍生的序列或由其组成。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子包含从生物或病毒的基因组的编码序列衍生的序列或由其组成。在一些实施方案中，本公开文本的RNA分子包含初级RNA转录物、前体信使RNA(前体mRNA)或信使RNA(mRNA)或由其组成。在一些实施方案中，本公开文本的RNA分子包含尚未加工的基因产物(例如转录物)或由其组成。在一些实施方案中，本公开文本的RNA分子包含已经进行转录后加工的基因产物(例如包含5'帽和3'多聚腺苷酸化信号的转录物)或由其组成。在一些实施方案中，本公开文本的RNA分子包含已经进行选择性剪接的基因产物(例如剪接变体)或由其组成。在一些实施方案中，本公开文本的RNA分子包含已经进行非编码序列和/或内含子序列的去除的基因产物(例如信使RNA(mRNA))或由其组成。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子包含从非编码序列衍生的序列(例如非编码RNA(ncRNA))或由其组成。在一些实施方案中，本公开文本的RNA分子包含核糖体RNA或由其组成。在一些实施方案中，本公开文本的RNA分子包含小ncRNA分子或由其组成。本公开文本的示例性小RNA分子包括但不限于微小RNA(miRNA)、小干扰(siRNA)、piwi相互作用RNA(piRNA)、核仁小RNA(snoRNA)、小核RNA(snRNA)、细胞外或外泌体RNA(exRNA)和小卡哈尔体特异性RNA(scaRNA)。在一些实施方案中，本公开文本的RNA分子包含长ncRNA分子或由其组成。本公开文本的示例性长RNA分子包括但不限于X染色体失活特异性转录物(Xist)和HOX转录物反义RNA(HOTAIR)。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在细胞内间隙中接触。在一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在胞质溶胶面中接触。在一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在核中接触。在一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在囊泡、细胞的膜结合区室或细胞器中接触。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在细胞外间隙中接触。在一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在外泌体中接触。在一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在脂质体、聚合物囊泡(polymersome)、胶束或纳米颗粒中接触。在一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在细胞外基质中接触。在一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在液滴中接触。在一些实施方案中，本公开文本的RNA分子与本公开文本的组合物在微流体液滴中接触。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的RNA分子包含单链序列或由其组成。在一些实施方案中，本公开文本的RNA分子包含双链序列或由其组成。在一些实施方案中，所述双链序列包含两个RNA分子。在一些实施方案中，所述双链序列包含一个RNA分子和一个DNA分子。在一些实施方案(包括其中所述双链序列包含一个RNA分子和一个DNA分子的那些实施方案)中，本公开文本的组合物选择性结合并任选地选择性切割所述RNA分子。
RNA结合内切核酸酶
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含核酸酶结构域或由其组成。在一些实施方案中，所述第二RNA结合蛋白以与RNA缔合的方式结合RNA。在一些实施方案中，所述第二RNA结合蛋白以切割RNA的方式与RNA缔合。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含RNA酶或由其组成。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶1或由其组成。在一些实施方案中，RNA酶1蛋白包含以下序列或由其组成：
KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGLCKPVNTFVHEPLVDVQNVCFQEKVTCKNGQGNCYKSNSSMHITDCRLTNGSRYPNCAYRTSPKERHIIVACEGSPYVPVHFDASVEDST(SEQ ID NO:20)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶4或由其组成。在一些实施方案中，RNA酶4蛋白包含以下序列或由其组成：
QDGMYQRFLRQHVHPEETGGSDRYCDLMMQRRKMTLYHCKRFNTFIHEDIWNIRSICSTTNIQCKNGKMNCHEGVVKVTDCRDTGSSRAPNCRYRAIASTRRVVIACEGNPQVPVHFDG(SEQ ID NO:21)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶6或由其组成。在一些实施方案中，RNA酶6蛋白包含以下序列或由其组成：
WPKRLTKAHWFEIQHIQPSPLQCNRAMSGINNYTQHCKHQNTFLHDSFQNVAAVCDLLSIVCKNRRHNCHQSSKPVNMTDCRLTSGKYPQCRYSAAAQYKFFIVACDPPQKSDPPYKLVPVHLDSIL(SEQ ID NO:22)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶7或由其组成。在一些实施方案中，RNA酶7蛋白包含以下序列或由其组成：
APARAGFCPLLLLLLLGLWVAEIPVSAKPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNTFLHEPFSSVAATCQTPKIACKNGDKNCHQSHGPVSLTMCKLTSGKYPNCRYKEKRQNKSYVVACKPPQKKDSQQFHLVPVHLDRVL(SEQ ID NO:23)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶8或由其组成。在一些实施方案中，RNA酶8蛋白包含以下序列或由其组成：
TSSQWFKTQHVQPSPQACNSAMSIINKYTERCKDLNTFLHEPFSSVAITCQTPNIACKNSCKNCHQSHGPMSLTMGELTSGKYPNCRYKEKHLNTPYIVACDPPQQGDPGYPLVPVHLDKVV(SEQ ID NO:24)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶2或由其组成。在一些实施方案中，RNA酶2蛋白包含以下序列或由其组成：
KPPQFTWAQWFETQHINMTSQQCTNAMQVINNYQRRCKNQNTFLLTTFANVVNVCGNPNMTCPSNKTRKNCHHSGSQVPLIHCNLTTPSPQNISNCRYAQTPANMFYIVACDNRDQRRDPPQYPVVPVHLDRII(SEQ ID NO:25)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶6PL或由其组成。在一些实施方案中，RNA酶6PL蛋白包含以下序列或由其组成：
DKRLRDNHEWKKLIMVQHWPETVCEKIQNDCRDPPDYWTIHGLWPDKSEGCNRSWPFNLEEIKKNWMEITDSSLPSPSMGPAPPRWMRSTPRRSTLAEAWNSTGSWTSTGGCALPPAALPSGDLCCRPSLTAGSRGVGVDLTALHQLLHVHYSATGIIPEECSEPTKPFQIILHHDHTEWVQSIGMPIWGTISSSESAIGKNEESQPACAVLSHDS(SEQID NO:26)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶L或由其组成。在一些实施方案中，RNA酶L蛋白包含以下序列或由其组成：
AAVEDNHLLIKAVQNEDVDLVQQLLEGGANVNFQEEEGGWTPLHNAVQMSREDIVELLLRHGADPVLRKKNGATPFILAAIAGSVKdLLKLFLSKGADVNECDFYGFTAFMEAAVYGKVKALKFLYKRGANVNLRRKTKEDQERLRKGGATALMDAAEKGHVEVLKILLDEMGADVNACDNMGRNALIHALLSSDDSDVEAITHLLLDHGADVNVRGERGKTPLILAVEKKHLGLVQRLLEQEHIEINDTDSDGKTALLLAVELKLKKIAELLCKRGASTDCGDLVMTARRNYDHSLVKVLLSHGAKEDFHPPAEDWKPQSSHWGAALKDLHRIYRPMIGKLKFFIDEKYKIADTSEGGIYLGFYEKQEVAVKTFCEGSPRAQREVSCLQSSRENSHLVTFYGSESHRGHLFVCVTLCEQTLEACLDVHRGEDVENEEDEFARNVLSSIFKAVQELHLSCGYTHQDLQPQNILIDSKKAAHLADFDKSIKWAGDPQEVKRDLEDLGRLVLYVVKKGSISFEDLKAQSNEEVVQLSPDEETKDLIHRLFHPGEHVRDCLSDLLGHPFFWTWESRYRTLRNVGNESDIKTRKSESEILRLLQPGPSEHSKSFDKWTTKINECVMKKMNKFYEKRGNFYQNTVGDLLKFIRNLGEHIDEEKHKKMKLKIGDPSLYFQKTFPDLVIYVYTKLQNTEYRKHFPQTHSPNKPQCDGAGGASGLASPGC(SEQ ID NO:27)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶T2或由其组成。在一些实施方案中，RNA酶T2蛋白包含以下序列或由其组成：
VQHWPETVCEKIQNDCRDPPDYWTIHGLWPDKSEGCNRSWPFNLEEIKDLLPEMRAYWPDVIHSFPNRSRFWKHEWEKHGTCAAQVDALNSQKKYFGRSLELYRELDLNSVLLKLGIKPSINYYQVADFKDALARVYGVIPKIQCLPPSQDEEVQTIGQIELCLTKQDQQLQNCTEPGEQPSPKQEVWLANGAAESRGLRVCEDGPVFYPPPKKTKH(SEQID NO:28)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶11或由其组成。在一些实施方案中，RNA酶11蛋白包含以下序列或由其组成：
EASESTMKIIKEEFTDEEMQYDMAKSGQEKQTIEILMNPILLVKNTSLSMSKDDMSSTLLTFRSLHYNDPKGNSSGNDKECCNDMTVWRKVSEANGSCKWSNNFIRSSTEVMRRVHRAPSCKFVQNPGISCCESLELENTVCQFTTGKQFPRCQYHSVTSLEKILTVLTGHSLMSWLVCGSKL(SEQ ID NO:29)。
在一些实施方案中，所述第二RNA结合蛋白包含RNA酶T2样蛋白或由其组成。在一些实施方案中，RNA酶T2样蛋白包含以下序列或由其组成：
XLGGADKRLRDNHEWKKLIMVQHWPETVCEKIQNDCRDPPDYWTIHGLWPDKSEGCNRSWPFNLEEIKDLLPEMRAYWPDVIHSFPNRSRFWKHEWEKHGTCAAQVDALNSQKKYFGRSLELYRELDLNSVLLKLGIKPSINYYQTTEEDLNLDVEPTTEDTAEEVTIHVLLHSALFGEIGPRRW(SEQ ID NO:30)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶或由其组成。
在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(K41R))多肽或由其组成。在一些实施方案中，RNA酶1(K41R)多肽包含以下序列或由其组成：
KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGRCRPVNTFVHEPLVDVQNVCFQEKVTCKNGQGNCYKSNSSMHITDCRLTNGSRYPNCAYRTSPKERHIIVACEGSPYVPVHFDASVEDST(SEQ ID NO:116)。
在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(K41R、D121E))多肽或由其组成。在一些实施方案中，RNA酶1(RNA酶1(K41R、D121E))多肽包含以下序列或由其组成：
KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGRCRPVNTFVHEPLVDVQNVCFQEKVTCKNGQGNCYKSNSSMHITDCRLTNGSRYPNCAYRTSPKERHIIVACEGSPYVPVHFEASVEDST(SEQ ID NO:117)。
在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(K41R、D121E、H119N))多肽或由其组成。在一些实施方案中，RNA酶1(RNA酶1(K41R、D121E、H119N))多肽包含以下序列或由其组成：
KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGRCRPVNTFVHEPLVDVQNVCFQEKVTCKNGQGNCYKSNSSMHITDCRLTNGSRYPNCAYRTSPKERHIIVACEGSPYVPVNFEASVEDST(SEQ ID NO:118)。
在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(H119N))多肽或由其组成。在一些实施方案中，RNA酶1(RNA酶1(H119N))多肽包含以下序列或由其组成：
KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGRCKPVNTFVHEPLVDVQNVCFQEKVTCKNGQGNCYKSNSSMHITDCRLTNGSRYPNCAYRTSPKERHIIVACEGSPYVPVNFDASVEDST(SEQ ID NO:119)。
在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽或由其组成。在一些实施方案中，RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽包含以下序列或由其组成：
KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGDCKPVNTFVHEPLVDVQNVCFQEKVTCKDGQGNCYKSNSSMHITDCRLTADSDYPNCAYRTSPKERHIIVACEGSPYVPVNFDASVEDST(SEQ ID NO:120)。在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽或由其组成。在一些实施方案中，RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N、K41R、D121E))多肽包含以下序列或由其组成：
KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGDCRPVNTFVHEPLVDVQNVCFQEKVTCKDGQGNCYKSNSSMHITDCRLTADSDYPNCAYRTSPKERHIIVACEGSPYVPVNFEASVEDST(SEQ ID NO:121)。
在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽或由其组成。在一些实施方案中，RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D))多肽包含以下序列或由其组成：
KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGDCKPVNTFVHEPLVDVQNVCFQEKVTCKDGQGNCYKSNSSMHITDCRLTADSDYPNCAYRTSPKERHIIVACEGSPYVPVHFDASVEDST(SEQ ID NO:122)。
在一些实施方案中，所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N、K41R、D121E))多肽或由其组成，所述多肽包含以下序列或由所述序列组成：
KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGDCRPVNTFVHEPLVDVQNVCFQEKVTCKDGQGNCYKSNSSMHITDCRLTADSDYPNCAYRTSPKERHIIVACEGSPYVPVNFEASVEDST(SEQ ID NO:208)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含NOB1多肽或由其组成。在一些实施方案中，NOB1多肽包含以下序列或由其组成：
APVEHVVADAGAFLRHAALQDIGKNIYTIREVVTEIRDKATRRRLAVLPYELRFKEPLPEYVRLVTEFSKKTGDYPSLSATDIQVLALTYQLEAEFVGVSHLKQEPQKVKVSSSIQHPETPLHISGFHLPYKPKPPQETEKGHSACEPENLEFSSFMFWRNPLPNIDHELQELLIDRGEDVPSEEEEEEENGFEDRKDDSDDDGGGWITPSNIKQIQQELEQCDVPEDVRVGCLTTDFAMQNVLLQMGLHVLAVNGMLIREARSYILRCHGCFKTTSDMSRVFCSHCGNKTLKKVSVTV(SEQ ID NO:31)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶V(ENDOV)或由其组成。在一些实施方案中，ENDOV蛋白包含以下序列或由其组成：
AFSGLQRVGGVDVSFVKGDSVRACASLVVLSFPELEVVYEESRMVSLTAPYVSGFLAFREVPFLLELVQQLREKEPGLMPQVLLVDGNGVLHHRGFGVACHLGVLTDLPCVGVAKKLLQVDGLENNALHKEKIRLLQTRGDSFPLLGDSGTVLGMALRSHDRSTRPLYISVGHRMSLEAAVRLTCCCCRFRIPEPVRQADICSREHIRKS(SEQ ID NO:32)。
在一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶G(ENDOG)或由其组成。在一些实施方案中，ENDOG蛋白包含以下序列或由其组成：
AELPPVPGGPRGPGELAKYGLPGLAQLKSRESYVLCYDPRTRGALWVVEQLRPERLRGDGDRRECDFREDDSVHAYHRATNADYRGSGFDRGHLAAAANHRWSQKAMDDTFYLSNVAPQVPHLNQNAWNNLEKYSRSLTRSYQNVYVCTGPLFLPRTEADGKSYVKYQVIGKNHVAVPTHFFKVLILEAAGGQIELRTYVMPNAPVDEAIPLERFLVPIESIERASGLLFVPNILARAGSLKAITAGSK(SEQ ID NO:33)。
在一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶D1(ENDOD1)或由其组成。在一些实施方案中，ENDOD1蛋白包含以下序列或由其组成：
RLVGEEEAGFGECDKFFYAGTPPAGLAADSHVKICQRAEGAERFATLYSTRDRIPVYSAFRAPRPAPGGAEQRWLVEPQIDDPNSNLEEAINEAEAITSVNSLGSKQALNTDYLDSDYQRGQLYPFSLSSDVQVATFTLTNSAPMTQSFQERWYVNLHSLMDRALTPQCGSGEDLYILTGTVPSDYRVKDKVAVPEFVWLAACCAVPGGGWAMGFVKHTRDSDIIEDVMVKDLQKLLPFNPQLFQNNCGETEQDTEKMKKILEVVNQIQDEERMVQSQKSSSPLSSTRSKRSTLLPPEASEGSSSFLGKLMGFIATPFIKLFQLIYYLVVAILKNIVYFLWCVTKQVINGIESCLYRLGSATISYFMAIGEELVSIPWKVLKVVAKVIRALLRILCCLLKAICRVLSIPVRVLVDVATFPVYTMGAIPIVCKDIALGLGGTVSLLFDTAFGTLGGLFQVVFSVCKRIGYKVTFDNSGEL(SEQ ID NO:34)。
在一些实施方案中，所述第二RNA结合蛋白包含人瓣状内切核酸酶-1(hFEN1)或由其组成。在一些实施方案中，hFEN1多肽包含以下序列或由其组成：
MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGGDVLQNEEGETTSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKRSERRAEAEKQLQQAQAAGAEQEVEKFTKRLVKVTKQHNDECKHLLSLMGIPYLDAPSEAEASCAALVKAGKVYAAATEDMDCLTFGSPVLMRHLTASEAKKLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRGIGPKRAVDLIQKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSEPNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTQGRLDDFFKVTGSLSSAKRKEPEPKGSTKKKAKTGAAGKFKRGK(SEQ ID NO:35)。
在一些实施方案中，所述第二RNA结合蛋白包含DNA修复内切核酸酶XPF(ERCC4)多肽或由其组成。在一些实施方案中，ERCC4多肽包含以下序列或由其组成：
MESGQPARRIAMAPLLEYERQLVLELLDTDGLVVCARGLGADRLLYHFLQLHCHPACLVLVLNTQPAEEEYFINQLKIEGVEHLPRRVTNEITSNSRYEVYTQGGVIFATSRILVVDFLTDRIPSDLITGILVYRAHRIIESCQEAFILRLFRQKNKRGFIKAFTDNAVAFDTGFCHVERVMRNLFVRKLYLWPRFHVAVNSFLEQHKPEVVEIHVSMTPTMLAIQTAILDILNACLKELKCHNPSLEVEDLSLENAIGKPFDKTIRHYLDPLWHQLGAKTKSLVQDLKILRTLLQYLSQYDCVTFLNLLESLRATEKAFGQNSGWLFLDSSTSMFINARARVYHLPDAKMSKKEKISEKMEIKEGEGILWG(SEQ ID NO:124)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含内切核酸酶III样蛋白1(NTHL)多肽或由其组成。在一些实施方案中，NTHL多肽包含以下序列或由其组成：
CSPQESGMTALSARMLTRSRSLGPGAGPRGCREEPGPLRRREAAAEARKSHSPVKRPRKAQRLRVAYEGSDSEKGEGAEPLKVPVWEPQDWQQQLVNIRAMRNKKDAPVDHLGTEHCYDSSAPPKVRRYQVLLSLMLSSQTKDQVTAGAMQRLRARGLTVDSILQTDDATLGKLIYPVGFWRSKVKYIKQTSAILQQHYGGDIPASVAELVALPGVGPKMAHLAMAVAWGTVSGIAVDTHVHRIANRLRWTKKATKSPEETRAALEEWLPRELWHEINGLLVGFGQQTCLPVHPRCHACLNQALCPAAQGL(SEQ ID NO:123)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含人斯库拉芬蛋白14(hSLFN14)多肽或由其组成。在一些实施方案中，hSLFN14多肽包含以下序列或由其组成：
ESTHVEFKRFTTKKVIPRIKEMLPHYVSAFANTQGGYVLIGVDDKSKEVVGCKWEKVNPDLLKKEIENCIEKLPTFHFCCEKPKVNFTTKILNVYQKDVLDGYVCVIQVEPFCCVVFAEAPDSWIMKDNSVTRLTAEQWVVMMLDTQSAPPSLVTDYNSCLISSASSARKSPGYPIKVHKFKEALQ(SEQ ID NO:36)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含人β-内酰胺酶样蛋白2(hLACTB2)多肽或由其组成。在一些实施方案中，hLACTB2多肽包含以下序列或由其组成：
TLQGTNTYLVGTGPRRILIDTGEPAIPEYISCLKQALTEFNTAIQEIVVTHWHRDHSGGIGDICKSINNDTTYCIKKLPRNPQREEIIGNGEQQYVYLKDGDVIKTEGATLRVLYTPGHTDDHMALLLEEENAIFSGDCILGEGTTVFEDLYDYMNSLKELLKIKADIIYPGHGPVIHNAEAKIQQYISHRNIREQQILTLFRENFEKSFTVMELVKIIYKNTPENLHEMAKHNLLLHLKKLEKEGKIFSNTDPDKKWKAHL(SEQ ID NO:37)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含无嘌呤/无嘧啶(AP)内切脱氧核糖核酸酶(APEX)多肽或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含无嘌呤/无嘧啶(AP)内切脱氧核糖核酸酶(APEX2)多肽或由其组成。在一些实施方案中，APEX2多肽包含以下序列或由其组成：
MLRVVSWNINGIRRPLQGVANQEPSNCAAVAVGRILDELDADIVCLQETKVTRDALTEPLAIVEGYNSYFSFSRNRSGYSGVATFCKDNATPVAAEEGLSGLFATQNGDVGCYGNMDEFTQEELRALDSEGRALLTQHKIRTWEGKEKTLTLINVYCPHADPGRPERLVFKMRFYRLLQIRAEALLAAGSHVIILGDLNTAHRPIDHWDAVNLECFEEDPGRKWMDSLLSNLGCQSASHVGPFIDSYRCFQPKQEGAFTCWSAVTGARHLNYGSRLDYVLGDRTLVIDTFQASFLLPEVMGSDHCPVGAVLSVSSVPAKQCPPLCTRFLPEFAGTQLKILRFLVPLEQSPVLEQSTLQHNNQTRVQTCQNKAQVRSTRPQPSQVGSSRGQKNLKSYFQPSPSCPQASPDIELPSLPLMSALMTPKTPEEKAVAKVVKGQAKTSEAKDEKELRTSFWKSVLAGPLRTPLCGGHREPCVMRTVKKPGPNLGRRFYMCARPRGPPTDPSSRCNFFLWSRPS(SEQ IDNO:38)。
在一些实施方案中，APEX2多肽包含以下序列或由其组成：MLRVVSWNINGIRRPLQGVANQEPSNCAAVAVGRILDELDADIVCLQETKVTRDALTEPLAIVEGYNSYFSFSRNRSGYSGVATFCKDNATPVAAEEGLSGLFATQNGDVGCYGNMDEFTQEELRALDSEGRALLTQHKIRTWEGKEKTLTLINVYCPHADPGRPERLVFKMRFYRLLQIRAEALLAAGSHVIILGDLNTAHRPIDHWDAVNLECFEEDPGRKWMDSLLSNLGCQSASHVGPFIDSYRCFQPKQEGAFTCWSAVTGARHLNYGSRLDYVLGDRTLVIDTFQASFLLPEVMGSDHCPVGAVLSVSSVPAKQCPPLCTRFLPEFAGTQLKILRFLVPLEQSP(SEQ ID NO:39)。
在一些实施方案中，所述第二RNA结合蛋白包含无嘌呤或无嘧啶位点裂解酶(APEX1)多肽或由其组成。在一些实施方案中，APEX1多肽包含以下序列或由其组成：
PKRGKKGAVAEDGDELRTEPEAKKSKTAAKKNDKEAAGEGPALYEDPPDQKTSPSGKPATLKICSWNVDGLRAWIKKKGLDWVKEEAPDILCLQETKCSENKLPAELQELPGLSHQYWSAPSDKEGYSGVGLLSRQCPLKVSYGIGDEEHDQEGRVIVAEFDSFVLVTAYVPNAGRGLVRLEYRQRWDEAFRKFLKGLASRKPLVLCGDLNVAHEEIDLRNPKGNKKNAGFTPQERQGFGELLQAVPLADSFRHLYPNTPYAYTFWTYMMNARSKNVGWRLDYFLLS(SEQ IDNO:125)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含血管生成素(ANG)多肽或由其组成。在一些实施方案中，ANG多肽包含以下序列或由其组成：
QDNSRYTHFLTQHYDAKPQGRDDRYCESIMRRRGLTSPCKDINTFIHGNKRSIKAICENKNGNPHRENLRISKSSFQVTTCKLHGGSPWPPCQYRATAGFRNVVVACENGLPVHLDQSIFRRP(SEQ ID NO:40)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含热反应蛋白12(HRSP12)多肽或由其组成。在一些实施方案中，HRSP12多肽包含以下序列或由其组成：
SSLIRRVISTAKAPGAIGPYSQAVLVDRTIYISGQIGMDPSSGQLVSGGVAEEAKQALKNMGEILKAAGCDFTNVVKTTVLLADINDFNTVNEIYKQYFKSNFPARAAYQVAALPKGSRIEIEAVAIQGPLTTASL(SEQ IDNO:41)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含含锌指CCCH型12A(ZC3H12A)多肽或由其组成。在一些实施方案中，ZC3H12A多肽包含以下序列或由其组成：
GGGTPKAPNLEPPLPEEEKEGSDLRPVVIDGSNVAMSHGNKEVFSCRGILLAVNWFLERGHTDITVFVPSWRKEQPRPDVPITDQHILRELEKKKILVFTPSRRVGGKRVVCYDDRFIVKLAYESDGIVVSNDTYRDLQGERQEWKRFIEERLLMYSFVNDKFMPPDDPLGRHGPSLDNFLRKKPLTLE(SEQ ID NO:42)。
在一些实施方案中，ZC3H12A多肽包含以下序列或由其组成：SGPCGEKPVLEASPTMSLWEFEDSHSRQGTPRPGQELAAEEASALELQMKVDFFRKLGYSSTEIHSVLQKLGVQADTNTVLGELVKHGTATERERQTSPDPCPQLPLVPRGGGTPKAPNLEPPLPEEEKEGSDLRPVVIDGSNVAMSHGNKEVFSCRGILLAVNWFLERGHTDITVFVPSWRKEQPRPDVPITDQHILRELEKKKILVFTPSRRVGGKRVVCYDDRFIVKLAYESDGIVVSNDTYRDLQGERQEWKRFIEERLLMYSFVNDKFMPPDDPLGRHGPSLDNFLRKKPLTLEHRKQPCPYGRKCTYGIKCRFFHPERPSCPQRSVADELRANALLSPPRAPSKDKNGRRPSPSSQSSSLLTESEQCSLDGKKLGAQASPGSRQEGLTQTYAPSGRSLAPSGGSGSSFGPTDWLPQTLDSLPYVSQDCLDSGIGSLESQMSELWGVRGGGPGEPGPPRAPYTGYSPYGSELPATAAFSAFGRAMGAGHFSVPADYPPAPPAFPPREYWSEPYPLPPPTSVLQEPPVQSPGAGRSPWGRAGSLAKEQASVYTKLCGVFPPHLVEAVMGRFPQLLDPQQLAAEILSYKSQHPSE(SEQ ID NO:43)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含反应性中间亚胺脱氨酶A(RIDA)多肽或由其组成。在一些实施方案中，RIDA多肽包含以下序列或由其组成：
SSLIRRVISTAKAPGAIGPYSQAVLVDRTIYISGQIGMDPSSGQLVSGGVAEEAKQALKNMGEILKAAGCDFTNVVKTTVLLADINDFNTVNEIYKQYFKSNFPARAAYQVAALPKGSRIEIEAVAIQGPLTTASL(SEQ IDNO:44)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含磷脂酶D家族成员6(PDL6)多肽或由其组成。在一些实施方案中，PDL6多肽包含以下序列或由其组成：
EALFFPSQVTCTEALLRAPGAELAELPEGCPCGLPHGESALSRLLRALLAARASLDLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNWTTQAIQNNRENVLITEDDEYVRLFLEEFERIWEQFNPTKYTFFPPKKSHGSCAPPVSRAGGRLLSWHRTCGTSSESQT(SEQ IDNO:126)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含线粒体核糖核酸酶P催化亚基(KIAA0391)多肽或由其组成。在一些实施方案中，KIAA0391多肽包含以下序列或由其组成：
KARYKTLEPRGYSLLIRGLIHSDRWREALLLLEDIKKVITPSKKNYNDCIQGALLHQDVNTAWNLYQELLGHDIVPMLETLKAFFDFGKDIKDDNYSNKLLDILSYLRNNQLYPGESFAHSIKTWFESVPGKQWKGQFTTVRKSGQCSGCGKTIESIQLSPEEYECLKGKIMRDVIDGGDQYRKTTPQELKRFENFIKSRPPFDVVIDGLNVAKMFPKVRESQLLLNVVSQLAKRNLRLLVLGRKHMLRRSSQWSRDEMEEVQKQASCFFADDISEDDPFLLYATLHSGNHCRFITRDLMRDHKACLPDAKTQRLFFKWQQGHQLAIVNRFPGSKLTFQRILSYDTVVQTTGDSWHIPYDEDLVERCSCEVPTKWLCLHQKT(SEQ ID NO:127)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含阿尔古蛋白2(AGO2)多肽或由其组成。
在本公开文本的组合物的一些实施方案中，AGO2多肽包含以下序列或由其组成：
SVEPMFRHLKNTYAGLQLVVVILPGKTPVYAEVKRVGDTVLGMATQCVQMKNVQRTTPQTLSNLCLKINVKLGGVNNILLPQGRPPVFQQPVIFLGADVTHPPAGDGKKPSIAAVVGSMDAHPNRYCATVRVQQHRQEIIQDLAAMVRELLIQFYKSTRFKPTRIIFYRDGVSEGQFQQVLHHELLAIREACIKLEKDYQPGITFIVVQKRHHTRLFCTDKNERVGKSGNIPAGTTVDTKITHPTEFDFYLCSHAGIQGTSRPSHYHVLWDDNRFSSDELQILTYQLCHTYVRCTRSVSIPAPAYYAHLVAFRARYHLVDKEHDSAEGSHTSGQSNGRDHQALAKAVQVHQDTLRTMYFA(SEQ ID NO:128)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含线粒体核酸酶EXOG(EXOG)多肽或由其组成。在一些实施方案中，EXOG多肽包含以下序列或由其组成：
QGAEGALTGKQPDGSAEKAVLEQFGFPLTGTEARCYTNHALSYDQAKRVPRWVLEHISKSKIMGDADRKHCKFKPDPNIPPTFSAFNEDYVGSGWSRGHMAPAGNNKFSSKAMAETFYLSNIVPQDFDNNSGYWNRIEMYCRELTERFEDVWVVSGPLTLPQTRGDGKKIVSYQVIGEDNVAVPSHLYKVILARRSSVSTEPLALGAFVVPNEAIGFQPQLTEFQVSLQDLEKLSGLVFFPHLDRTSDIRNICSVDTCKLLDFQEFTLYLSTRKIEGARSVLRLEKIMENLKNAEIEPDDYFMSRYEKKLEELKAKEQSGTQIRKPS(SEQ ID NO:129)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含含锌指CCCH型12D(ZC3H12D)多肽或由其组成。在一些实施方案中，ZC3H12D多肽包含以下序列或由其组成：
EHPSKMEFFQKLGYDREDVLRVLGKLGEGALVNDVLQELIRTGSRPGALEHPAAPRLVPRGSCGVPDSAQRGPGTALEEDFRTLASSLRPIVIDGSNVAMSHGNKETFSCRGIKLAVDWFRDRGHTYIKVFVPSWRKDPPRADTPIREQHVLAELERQAVLVYTPSRKVHGKRLVCYDDRYIVKVAYEQDGVIVSNDNYRDLQSENPEWKWFIEQRLLMFSFVNDRFMPPDDPLGRHGPSLSNFLSRKPKPPEPSWQHCPYGKKCTYGIKCKFYHPERPHHAQLAVADELRAKTGARPGAGAEEQRPPRAPGGSAGARAAPREPFAHSLPPARGSPDLAALRGSFSRLAFSDDLGPLGPPLPVPACSLTPRLGGPDWVSAGGRVPGPLSLPSPESQFSPGDLPPPPGLQLQPRGEHRPRDLHGDLLSPRRPPDDPWARPPRSDRFPGRSVWAEPAWGDGATGGLSVYATEDDEGDARARARIALYSVFPRDQVDRVMAAFPELSDLARLILLVQRCQSAGAPLGKP(SEQ ID NO:130)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含内质网核信号转导蛋白2(ERN2)多肽或由其组成。在一些实施方案中，ERN2多肽包含以下序列或由其组成：
RQQQPQVVEKQQETPLAPADFAHISQDAQSLHSGASRRSQKRLQSPSKQAQPLDDPEAEQLTVVGKISFNPKDVLGRGAGGTFVFRGQFEGRAVAVKRLLRECFGLVRREVQLLQESDRHPNVLRYFCTERGPQFHYIALELCRASLQEYVENPDLDRGGLEPEVVLQQLMSGLAHLHSLHIVHRDLKPGNILITGPDSQGLGRVVLSDFGLCKKLPAGRCSFSLHSGIPGTEGWMAPELLQLLPPDSPTSAVDIFSAGCVFYYVLSGGSHPFGDSLYRQANILTGAPCLAHLEEEVHDKVVARDLVGAMLSPLPQPRPSAPQVLAHPFFWSRAKQLQFFQDVSDWLEKESEQEPLVRALEAGGCAVVRDNWHEHISMPLQTDLRKFRSYKGTSVRDLLRAVRNKKHHYRELPVEVRQALGQVPDGFVQYFTNRFPRLLLHTHRAMRSCASESLFLPYYPPDSEARRPCPGATGR(SEQ ID NO:131)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含回力球mRNA监督和核糖体挽救因子(PELO)多肽或由其组成。在一些实施方案中，PELO多肽包含以下序列或由其组成：
KLVRKNIEKDNAGQVTLVPEEPEDMWHTYNLVQVGDSLRASTIRKVQTESSTGSVGSNRVRTTLTLCVEAIDFDSQACQLRVKGTNIQENEYVKMGAYHTIELEPNRQFTLAKKQWDSVVLERIEQACDPAWSADVAAVVMQEGLAHICLVTPSMTLTRAKVEVNIPRKRKGNCSQHDRALERFYEQVVQAIQRHIHFDVVKCILVASPGFVREQFCDYLFQQAVKTDNKLLLENRSKFLQVHASSGHKYSLKEALCDPTVASRLSDTKAAGEVKALDDFYKMLQHEPDRAFYGLKQVEKANEAMAIDTLLISDELFRHQDVATRSRYVRLVDSVKENAGTVRIFSSLHVSGEQLSQLTGVAAILRFPVPELSDQEGDSSSEED(SEQ ID NO:132)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含YBEY金属肽酶(YBEY)多肽或由其组成。在一些实施方案中，YBEY多肽包含以下序列或由其组成：
SLVIRNLQRVIPIRRAPLRSKIEIVRRILGVQKFDLGIICVDNKNIQHINRIYRDRNVPTDVLSFPFHEHLKAGEFPQPDFPDDYNLGDIFLGVEYIFHQCKENEDYNDVLTVTATHGLCHLLGFTHGTEAEWQQMFQKEKAVLDELGRRTGTRLQPLTRGLFGGS(SEQ ID NO:133)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含剪切和多聚腺苷酸化特异性因子4样蛋白(CPSF4L)多肽或由其组成。在一些实施方案中，CPSF4L多肽包含以下序列或由其组成：QEVIAGLERFTFAFEKDVEMQKGTGLLPFQGMDKSASAVCNFFTKGLCEKGKLCPFRHDRGEKMVVCKHWLRGLCKKGDHCKFLHQYDLTRMPECYFYSKFGDCSNKECSFLHVKPAFKSQDCPWYDQGFCKDGPLCKYRHVPRIMCLNYLVGFCPEGPKCQFAQKIREFKLLPGSKI(SEQ ID NO:134)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含hCG_2002731多肽或由其组成。在一些实施方案中，hCG_2002731多肽包含以下序列或由其组成：
KLVRKNIEKDNAGQVTLVPEEPEDMWHTYNLVQVGDSLRASTIRKVQTESSTGSVGSNRVRTTLTLCVEAIDFDSQACQLRVKGTNIQENEYVKMGAYHTIELEPNRQFTLAKKQWDSVVLERIEQACDPAWSADVAAVVMQEGLAHICLVTPSMTLTRAKVEVNIPRKRKGNCSQHDRALERFYEQVVQAIQRHIHFDVVKCILVASPGFVREQFCDYMFQQAVKTDNKLLLENRSKFLQVHASSGHKYSLKEALCDPTVASRLSDTKAAGEVKALDDFYKMLQHEPDRAFYGLKQVEKANEAMAIDTLLISDELFRHQDVATRSRYVRLVDSVKENAGTVRIFSSLHVSGEQLSQLTGVAAILRFPVPELSDQEGDSSSEED(SEQ ID NO:135)。
在一些实施方案中，hCG_2002731多肽包含以下序列或由其组成：
DPAWSADVAAVVMQEGLAHICLVTPSMTLTRAKVEVNIPRKRKGNCSQHDRALERFYEQVVQAIQRHIHFDVVKCILVASPGFVREQFCDYMFQQAVKTDNKLLLENRSKFLQVHASSGHKYSLKEALCDPTVASRLSDTKAAGEVKALDDFYKMLQHEPDRAFYGLKQVEKANEAMAIDTLLISDELFRHQDVATRSRYVRLVDSVKENAGTVRIFSSLHVSGEQLSQLTGVAAILRFPVPELSDQEGDSSSEED(SEQ ID NO:136)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含切除修复交叉互补组1(ERCC1)多肽或由其组成。在一些实施方案中，ERCC1多肽包含以下序列或由其组成：
MDPGKDKEGVPQPSGPPARKKFVIPLDEDEVPPGVRGNPVLKFVRNVPWEFGDVIPDYVLGQSTCALFLSLRYHNLHPDYIHGRLQSLGKNFALRVLLVQVDVKDPQQALKELAKMCILADCTLILAWSPEEAGRYLETYKAYEQKPADLLMEKLEQDFVSRVTECLTTVKSVNKTDSQTLLTTFGSLEQLIAASREDLALCPGLGPQK(SEQ ID NO:137)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含ras相关C3肉毒杆菌毒素底物1亚型(RAC1)多肽或由其组成。在一些实施方案中，RAC1多肽包含以下序列或由其组成：KESRAKKFQRQHMDSDSSPSSSSTYCNQMMRRRNMTQGRCKPVNTFVHEPLVDVQNVCFQEKVTCKNGQGNCYKSNSSMHITDCRLTNGSRYPNCAYRTSPKERHIIVACEGSPYVPVHFDASVEDST(SEQ ID NO:138)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含核糖核酸酶A A1(RAA1)多肽或由其组成。在一些实施方案中，RAA1多肽包含以下序列或由其组成：
QDNSRYTHFLTQHYDAKPQGRDDRYCESIMRRRGLTSPCKDINTFIHGNKRSIKAICENKNGNPHRENLRISKSSFQVTTCKLHGGSPWPPCQYRATAGFRNVVVACENGLPVHLDQSIFRRP(SEQ ID NO:139)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含Ras相关蛋白(RAB1)多肽或由其组成。在一些实施方案中，RAB1多肽包含以下序列或由其组成：
GLGLVQPSYGQDGMYQRFLRQHVHPEETGGSDRYCNLMMQRRKMTLYHCKRFNTFIHEDIWNIRSICSTTNIQCKNGKMNCHEGVVKVTDCRDTGSSRAPNCRYRAIASTRRVVIACEGNPQVPVHFDG(SEQ ID NO:140)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含DNA复制解旋酶/核酸酶2(DNA2)多肽或由其组成。在一些实施方案中，DNA2多肽包含以下序列或由其组成：
XSAVDNILLKLAKFKIGFLRLGQIQKVHPAIQQFTEQEICRSKSIKSLALLEELYNSQLIVATTCMGINHPIFSRKIFDFCIVDEASQISQPICLGPLFFSRRFVLVGDHQQLPPLVLNREARALGMSESLFKRLEQNKSAVVQLTVQYRMNSKIMSLSNKLTYEGKLECGSDKVANAVINLRHFKDVKLELEFYADYSDNPWLMGVFEPNNPVCFLNTDKVPAPEQVEKGGVSNVTEAKLIVFLTSIFVKAGCSPSDIGIIAPYRQQLKIINDLLARSIGMVEVNTVDKYQGRDKSIVLVSFVRSNKDGTVGELLKDWRRLNVAITRAKHKLILLGCVPSLNCYPPLEKLLNHLNSEKLISFFFCIWSHLIALL(SEQ ID NO:141)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含FLJ35220多肽或由其组成。在一些实施方案中，FLJ35220多肽包含以下序列或由其组成：
MALRSHDRSTRPLYISVGHRMSLEAAVRLTCCCCRFRIPEPVRQADICSREHIRKSLGLPGPPTPRSPKAQRPVACPKGDSGESSALC(SEQ ID NO:142)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含FLJ13173多肽或由其组成。在一些实施方案中，FLJ13173多肽包含以下序列或由其组成：
CYTNHALSYDQAKRVPRWVLEHISKSKIMGDADRKHCKFKPDPNIPPTFSAFNEDYVGSGWSRGHMAPAGNNKFSSKAMAETFYLSNIVPQDFDNNSGYWNRIEMYCRELTERFEDVWVVSGPLTLPQTRGDGKKIVSYQVIGEDNVAVPSHLYKVILARRSSVSTEPLALGAFVVPNEAIGFQPQLTEFQVSLQDLEKLSGLVFFPHLDRT(SEQ IDNO:143)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含特诺伊林跨膜蛋白(TENM)多肽或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含特诺伊林跨膜蛋白1(TENM1)多肽或由其组成。在一些实施方案中，TENM1多肽包含以下序列或由其组成：
VTVSQMTSVLNGKTRRFADIQLQHGALCFNIRYGTTVEEEKNHVLEIARQRAVAQAWTKEQRRLQEGEEGIRAWTEGEKQQLLSTGRVQGYDGYFVLSVEQYLELSDSANNIHFMRQSEIGRR(SEQ ID NO:144)。
在一些实施方案中，所述第二RNA结合蛋白包含特诺伊林跨膜蛋白2(TENM2)多肽或由其组成。在一些实施方案中，TENM2多肽包含以下序列或由其组成：
TVSQPTLLVNGKTRRFTNIEFQYSTLLLSIRYGLTPDTLDEEKARVLDQARQRALGTAWAKEQQKARDGREGSRLWTEGEKQQLLSTGRVQGYEGYYVLPVEQYPELADSSSNIQFLRQNEMGKR(SEQ ID NO:145)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含核糖核酸酶κ(RNA酶K)多肽或由其组成。在一些实施方案中，RNA酶K多肽包含以下序列或由其组成：
MGWLRPGPRPLCPPARASWAFSHRFPSPLAPRRSPTPFFMASLLCCGPKLAACGIVLSAWGVIMLIMLGIFFNVHSAVLIEDVPFTEKDFENGPQNIYNLYEQVSYNCFIAAGLYLLLGGFSFCQVRLNKRKEYMVR(SEQ IDNO:204)。
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含转录激活因子样效应物核酸酶(TALEN)多肽或所述多肽的核酸酶结构域或由其组成。在一些实施方案中，TALEN多肽包含以下序列或由其组成：
Figure BDA0002919433300000921
Figure BDA0002919433300000931
在一些实施方案中，TALEN多肽包含以下序列或由其组成：
Figure BDA0002919433300000932
Figure BDA0002919433300000941
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含锌指核酸酶多肽或所述多肽的核酸酶结构域或由其组成。在一些实施方案中，所述第二RNA结合蛋白包含ZNF638多肽或所述多肽的核酸酶结构域或由其组成。在一些实施方案中，ZNF638多肽多肽包含以下序列或由其组成：
Figure BDA0002919433300000942
Figure BDA0002919433300000951
在本公开文本的组合物的一些实施方案中，所述第二RNA结合蛋白包含从人SMG6蛋白衍生的PIN结构域或由其组成，所述人SMG6蛋白通常也称为端粒酶结合蛋白EST1A亚型3，NCBI参考序列：NP_001243756.1。在一些实施方案中，来自hSMG6的PIN在本文中以Cas融合蛋白的形式并作为内部对照使用，例如但不限于参见图9，其显示了PIN-dSauCas9、PIN-dSauCas9dHNH、PIN-dSPCas9和dcjeCas9-PIN。
在本公开文本的组合物的一些实施方案中，所述组合物还包含(a)包含特异性结合于RNA分子内的gRNA的序列；以及(b)编码核酸酶的序列。在一些实施方案中，核酸酶包含从CRISPR/Cas蛋白分离或衍生的序列。在一些实施方案中，所述CRISPR/Cas蛋白是从以下中的任一种分离或衍生的：I型、IA型、IB型、IC型、ID型、IE型、IF型、IU型、III型、IIIA型、IIIB型、IIIC型、IIID型、IV型、IVA型、IVB型、II型、IIA型、IIB型、IIC型、V型或VI型CRISPR/Cas蛋白。在一些实施方案中，核酸酶包含从TALEN或其核酸酶结构域分离或衍生的序列。在一些实施方案中，核酸酶包含从锌指核酸酶或其核酸酶结构域分离或衍生的序列。
融合蛋白
在本公开文本的组合物和方法的一些实施方案中，所述组合物包含编码靶RNA结合融合蛋白的序列，所述序列包含(a)编码第一RNA结合多肽或其部分的序列；以及(b)编码第二RNA结合多肽的序列，其中所述第一RNA结合多肽结合靶RNA，并且其中所述第二RNA结合多肽包含RNA-核酸酶活性。
在一些实施方案中，靶RNA结合融合蛋白是RNA指导的靶RNA结合融合蛋白。RNA指导的靶RNA结合融合蛋白包含至少一种RNA结合多肽，其对应于将所述RNA结合多肽指导至靶RNA的gRNA。RNA指导的靶RNA结合融合蛋白包括但不限于RNA结合多肽，其是基于CRISPR/Cas的RNA结合多肽或其部分。
在一些实施方案中，靶RNA结合融合蛋白不是RNA指导的靶RNA结合融合蛋白，并且因此包含至少一种RNA结合多肽，其能够在没有相应gRNA序列的情况下结合靶RNA。此类非指导的RNA结合多肽包括但不限于作为PUF(Pumilio和FBF同源家族)的至少一种RNA结合蛋白或其RNA结合部分。这种类型的RNA结合多肽可以用于代替gRNA指导的RNA结合蛋白如CRISPR/Cas。参与介导mRNA稳定性和翻译的PUF蛋白(以果蝇(Drosophila)Pumilio和秀丽隐杆线虫(C.elegans)fem-3结合因子命名)的独特RNA识别模式是本领域中熟知的。也是本领域中已知的人Pumilio1的PUF结构域与同源RNA序列紧密结合，并且可以修饰其特异性。其含有八个PUF重复，它们识别八个保守RNA碱基，且每个重复识别单个碱基。由于每个重复中的两条氨基酸侧链识别相应碱基的Watson-Crick边缘并决定该重复的特异性，PUF结构域可以被设计为特异性结合大多数8-nt RNA。Wang等人,Nat Methods.2009；6(11):825-830。还参见WO 2012/068627，将其通过引用以其整体并入本文。
在本公开文本的非指导的RNA结合融合蛋白的一些实施方案中，所述融合蛋白包含作为PUMBY(基于Pumilio的联合体)蛋白的至少一种RNA结合蛋白或其RNA结合部分。已经以天然和修饰形式广泛用于靶向RNA的RNA结合蛋白PumHD(Pumilio同源结构域，PUF家族的成员)已经被工程化以产生一组四个规范蛋白质模块，其中的每个靶向一个RNA碱基。这些模块(即，Pumby，代表基于Pumilio的联合体)可以以不同组成和长度的链进行链状结合，以结合所需靶RNA。此类Pumby-RNA相互作用的特异性高，且Pumby链与携带相对于靶序列的三个或更多个错配的RNA序列的结合不可检测。Katarzyna等人,PNAS,2016；113(19):E2579-E2588。还参见US 2016/0238593，将其通过引用以其整体并入本文。
在本公开文本的组合物的一些实施方案中，所述第一RNA结合蛋白包含Pumilio和FBF(PUF)蛋白。在一些实施方案中，所述第一RNA结合蛋白包含基于Pumilio的联合体(PUMBY)蛋白。在一些实施方案中，本公开文本的PUF1蛋白包含以下的氨基酸序列或由其组成：
Figure BDA0002919433300000971
在一些实施方案中，本公开文本的PUF3蛋白包含以下的氨基酸序列或由其组成：
Figure BDA0002919433300000972
Figure BDA0002919433300000981
Figure BDA0002919433300000982
在一些实施方案中，本公开文本的PUF4蛋白包含以下的氨基酸序列或由其组成：
Figure BDA0002919433300000983
在一些实施方案中，本公开文本的PUF5蛋白包含以下的氨基酸序列或由其组成：
Figure BDA0002919433300000984
Figure BDA0002919433300000991
Figure BDA0002919433300000992
在一些实施方案中，本公开文本的PUF6蛋白包含以下的氨基酸序列或由其组成：
Figure BDA0002919433300000993
Figure BDA0002919433300000994
在一些实施方案中，本公开文本的PUF7蛋白包含以下的氨基酸序列或由其组成：
Figure BDA0002919433300000995
Figure BDA0002919433300000996
在一些实施方案中，本公开文本的PUF8蛋白包含以下的氨基酸序列或由其组成：
Figure BDA0002919433300000997
Figure BDA0002919433300001001
Figure BDA0002919433300001002
在一些实施方案中，本公开文本的PUF9蛋白包含以下的氨基酸序列或由其组成：
Figure BDA0002919433300001003
在本公开文本的组合物的一些实施方案中，至少一种RNA结合蛋白或其RNA结合部分是PPR蛋白。PPR蛋白(从植物衍生的具有三角状五肽重复(PPR)基序的蛋白质)是核编码的并且仅在RNA水平上受控制细胞器(叶绿体和线粒体)，切割，翻译，剪接，RNA编辑，特异性作用于RNA稳定性的基因。PPR蛋白通常是35个氨基酸的基序，并且具有以下结构，其中PPR基序是约10个连续氨基酸。PPR基序的组合可以用于与RNA的序列选择性结合。PPR蛋白通常由约10个重复结构域的PPR基序构成。PPR结构域或RNA结合结构域可以被配置为无催化活性的。将WO 2013/058404通过引用以其整体并入本文。
在一些实施方案中，本文公开的融合蛋白在所述至少两种RNA结合多肽之间包含接头。在一些实施方案中，所述接头是肽接头。在一些实施方案中，所述肽接头包含三肽GGS的一个或多个重复。在其他实施方案中，所述接头是非肽接头。在一些实施方案中，所述非肽接头包含聚乙二醇(PEG)、聚丙二醇(PPG)、共-聚(乙二醇/丙二醇)、聚氧乙烯(POE)、聚氨基甲酸酯、聚膦腈、多糖、葡聚糖、聚乙烯醇、聚乙烯吡咯烷酮、聚乙烯基乙醚、聚丙烯酰胺、聚丙烯酸酯、聚氰基丙烯酸酯、脂质聚合物、甲壳素、透明质酸、肝素或烷基接头。
在一些实施方案中，所述至少一种RNA结合蛋白不需要多聚化以用于RNA结合活性。在一些实施方案中，所述至少一种RNA结合蛋白不是多聚体复合物的单体。在一些实施方案中，多聚体蛋白复合物不包含所述RNA结合蛋白。在一些实施方案中，所述至少一种RNA结合蛋白与所述RNA分子内的靶序列选择性结合。在一些实施方案中，所述至少一种RNA结合蛋白不包含对所述RNA分子内的第二序列的亲和力。在一些实施方案中，所述至少一种RNA结合蛋白不包含对所述RNA分子内的第二序列的高亲和力或不选择性结合所述第二序列。在一些实施方案中，所述至少一种RNA结合蛋白包含在2个与1300个之间的氨基酸，包括端点。
在一些实施方案中，本文公开的融合蛋白的所述至少一种RNA结合蛋白还包含编码核定位信号(NLS)的序列。在一些实施方案中，核定位信号(NLS)定位于所述RNA结合蛋白的3'。在一些实施方案中，所述至少一种RNA结合蛋白包含在所述蛋白质的C末端的NLS。在一些实施方案中，所述至少一种RNA结合蛋白还包含编码第一NLS的第一序列和编码第二NLS的第二序列。在一些实施方案中，所述第一NLS或所述第二NLS定位于所述RNA结合蛋白的3'。在一些实施方案中，所述至少一种RNA结合蛋白包含在所述蛋白质的C末端的第一NLS或第二NLS。在一些实施方案中，所述至少一种RNA结合蛋白还包含NES(核输出信号)或其他肽标签或分泌信号。
在一些实施方案中，本文公开的融合蛋白包含所述至少一种RNA结合蛋白作为第一RNA结合蛋白以及包含核酸酶结构域或由其组成的第二RNA结合蛋白。
在一些实施方案中，所述第二RNA结合多肽被可操作地配置到在所述第一RNA结合多肽的C末端的第一RNA结合多肽。在一些实施方案中，所述第二RNA结合多肽被可操作地配置到在所述第一RNA结合多肽的N末端的第一RNA结合多肽。例如，一种这样的示例性融合蛋白是E99，其被配置为使得RNA酶1(R39D、N67D、N88A、G89D、R19D、H119N、K41R)位于SpyCas9的N末端；而另一种示例性融合蛋白E100被配置为使得RNA酶1(R39D、N67D、N88A、G89D、R19D、H119N、K41R)位于SpyCas9的C末端。参见图6。
载体
在本公开文本的组合物和方法的一些实施方案中，载体包含本公开文本的指导RNA。在一些实施方案中，所述载体包含本公开文本的至少一种指导RNA。在一些实施方案中，所述载体包含本公开文本的一种或多种指导RNA。在一些实施方案中，所述载体包含本公开文本的两种或更多种指导RNA。在一些实施方案中，所述载体还包含本公开文本的融合蛋白。在一些实施方案中，所述融合蛋白包含第一RNA结合蛋白和第二RNA结合蛋白。
在本公开文本的组合物和方法的一些实施方案中，第一载体包含本公开文本的指导RNA，并且第二载体包含本公开文本的融合蛋白。在一些实施方案中，所述第一载体包含本公开文本的至少一种指导RNA。在一些实施方案中，所述第一载体包含本公开文本的一种或多种指导RNA。在一些实施方案中，所述第一载体包含本公开文本的两种或更多种指导RNA。在一些实施方案中，所述融合蛋白包含第一RNA结合蛋白和第二RNA结合蛋白。在一些实施方案中，所述第一载体和所述第二载体是相同的。在一些实施方案中，所述第一载体和所述第二载体是不同的。
在本公开文本的组合物和方法的一些实施方案中，所述载体是或包含“双组分RNA靶向系统”的组分，所述双组分RNA靶向系统包含(a)编码本公开文本的靶向RNA的融合蛋白的核酸序列；以及(b)单一指导RNA(sgRNA)序列，其包含：在其5'端，与靶RNA序列杂交或结合的RNA序列(或间隔子序列)；和在其3'端，能够与所述融合蛋白的CRISPR/Cas蛋白结合或缔合的RNA序列(或支架序列)；并且其中所述双组分RNA靶向系统在PAMmer不存在的情况下识别并改变细胞中的所述靶RNA。在一些实施方案中，所述双组分系统的序列在单一载体中。在一些实施方案中，所述双组分系统的间隔子序列靶向选自以下的重复序列：CUG、CCUG、CAG和GGGGCC。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的载体是病毒载体。在一些实施方案中，所述病毒载体包含从逆转录病毒分离或衍生的序列。在一些实施方案中，所述病毒载体包含从慢病毒分离或衍生的序列。在一些实施方案中，所述病毒载体包含从腺病毒分离或衍生的序列。在一些实施方案中，所述病毒载体包含从腺相关病毒(AAV)分离或衍生的序列。在一些实施方案中，所述病毒载体无复制能力。在一些实施方案中，所述病毒载体是分离的或重组的。在一些实施方案中，所述病毒载体是自身互补的。
在本公开文本的组合物和方法的一些实施方案中，所述病毒载体包含从腺相关病毒(AAV)分离或衍生的序列。在一些实施方案中，所述病毒载体包含从血清型AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9、AAV10、AAV11或AAV12的AAV分离或衍生的反向末端重复序列或衣壳序列。在一些实施方案中，所述病毒载体无复制能力。在一些实施方案中，所述病毒载体是分离的或重组的(rAAV)。在一些实施方案中，所述病毒载体是自身互补的(scAAV)。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的载体是非病毒载体。在一些实施方案中，所述载体包含以下项或由其组成：纳米颗粒、胶束、脂质体或阳离子脂质体/DNA复合物(lipoplex)、聚合物囊泡、聚合物/DNA复合物(polyplex)或树枝状聚合物。在一些实施方案中，所述载体是表达载体或重组表达系统。如本文所用，术语“重组表达系统”是指用于表达通过重组形成的某些遗传物质的遗传构建体。
在本公开文本的组合物和方法的一些实施方案中，本文提供的表达载体、病毒载体或非病毒载体包括但不限于表达控制元件。如本文所用的“表达控制元件”是指调节编码序列如基因的表达的任何序列。示例性表达控制元件包括但不限于启动子、增强子、微小RNA、转录后调节元件、多聚腺苷酸化信号序列和内含子。例如，表达控制元件可以是组成型的、诱导型的、阻抑型的或组织特异性的。“启动子”是以下控制序列，其是多核苷酸序列中控制转录起始和速率的区域。它可以含有调节蛋白和分子可以结合的遗传元件，如RNA聚合酶和其他转录因子。在一些实施方案中，启动子对表达的控制是组织特异性的。非限制性的示例性启动子包括CMV、CBA、CAG、Cbh、EF-1a、PGK、UBC、GUSB、UCOE、hAAT、TBG、结蛋白(Desmin)、MCK、C5-12、NSE、突触蛋白(Synapsin)、PDGF、MecP2、CaMKII、mGluR2、NFL、NFH、nβ2、PPE、ENK、EAAT2、GFAP、MBP和U6启动子。“增强子”是DNA中可以由激活蛋白结合以增加转录的可能性或频率的区域。非限制性的示例性增强子和转录后调节元件包括CMV增强子和WPRE。
在本公开文本的组合物和方法的一些实施方案中，本文提供的表达载体、病毒载体或非病毒载体包括但不限于用于建构“多顺反子(multicistronic)”或“多顺反子(polycistronic)”或“双顺反子”或“三顺反子”构建体(即，具有双重或三重或多重编码区或外显子)的载体元件，如IRES或2A肽位点，并且因此将具有从mRNA表达来自单一构建体的两种或更多种蛋白质的能力。多顺反子载体从同一mRNA同时表达两种或更多种单独蛋白质。最广泛用于构建多顺反子构型的两种策略是通过使用IRES或2A自切割位点。“IRES”是指用于多顺反子载体构建体内的病毒、原核或真核来源的内部核糖体进入位点或其部分。在一些实施方案中，IRES是允许以非帽依赖性方式进行翻译起始的RNA元件。术语“自切割肽”或“编码自切割肽的序列”或“2A自切割位点”是指在载体构建体内用于并入位点以促进核糖体跳跃且因此从单一启动子产生两种多肽的连接序列，此类自切割肽包括但不限于T2A和P2A肽或编码自切割肽的序列。
在一些实施方案中，所述载体是病毒载体。在一些实施方案中，所述载体是腺病毒载体、腺相关病毒(AAV)载体或慢病毒载体。在一些实施方案中，所述载体是逆转录病毒载体、腺病毒/逆转录病毒嵌合体载体、单纯疱疹病毒I或II载体、细小病毒载体、网状内皮组织增殖病病毒载体、脊髓灰质炎病毒载体、乳头状瘤病毒载体、痘苗病毒载体或者并入两种或更多种病毒载体的有利方面的任何杂合或嵌合载体。在一些实施方案中，所述载体还包含与多核苷酸可操作地连接的一种或多种表达控制元件。在一些实施方案中，所述载体还包含一种或多种选择标记。在一些实施方案中，所述AAV载体具有低毒性。在一些实施方案中，所述AAV载体不并入宿主基因组中，从而具有低的引起插入诱变的概率。在一些实施方案中，所述AAV载体可以编码4.5kb至4.75kb的一系列总多核苷酸。在一些实施方案中，可以用于任何本文所述的组合物、系统、方法和试剂盒中的示例性AAV载体可以包括AAV1载体、修饰的AAV1载体、AAV2载体、修饰的AAV2载体、AAV3载体、修饰的AAV3载体、AAV4载体、修饰的AAV4载体、AAV5载体、修饰的AAV5载体、AAV6载体、修饰的AAV6载体、AAV7载体、修饰的AAV7载体、AAV8载体、AAV9载体、AAV.rh10载体、修饰的AAV.rh10载体、AAV.rh32/33载体、修饰的AAV.rh32/33载体、AAV.rh43载体、修饰的AAV.rh43载体、AAV.rh64R1载体和修饰的AAV.rh64R1载体及其任何组合或等效物。在一些实施方案中，所述慢病毒载体是有整合酶能力的慢病毒载体(integrase-competent lentiviralvector，ICLV)。在一些实施方案中，所述慢病毒载体可以是指转基因质粒载体，以及与相关质粒(例如，包装质粒、rev表达质粒、包膜质粒)结合的转基因质粒载体，以及能够通过病毒或病毒样进入机制将外源核酸引入细胞中的基于慢病毒的颗粒。慢病毒载体是本领域中熟知的(参见例如，Trono D.(2002)Lentiviral vectors,New York:Spring-Verlag Berlin Heidelberg和Durand等人(2011)Viruses 3(2):132-159doi:10.3390/v3020132)。在一些实施方案中，可以用于任何本文所述的组合物、系统、方法和试剂盒中的示例性慢病毒载体可以包括人免疫缺陷病毒(HIV)1载体、修饰的人免疫缺陷病毒(HIV)1载体、人免疫缺陷病毒(HIV)2载体、修饰的人免疫缺陷病毒(HIV)2载体、白领白眉猴(sooty mangabey)猿猴免疫缺陷病毒(SIVSM)载体、修饰的白领白眉猴猿猴免疫缺陷病毒(SIVSM)载体、非洲绿猴猿猴免疫缺陷病毒(SIVAGM)载体、修饰的非洲绿猴猿猴免疫缺陷病毒(SIVAGM)载体、马传染性贫血病毒(EIAV)载体、修饰的马传染性贫血病毒(EIAV)载体、猫免疫缺陷病毒(FIV)载体、修饰的猫免疫缺陷病毒(FIV)载体、维斯纳/梅迪病毒(Visna/maedi virus)(VNV/VMV)载体、修饰的维斯纳/梅迪病毒(VNV/VMV)载体、羊关节炎-脑炎病毒(CAEV)载体、修饰的羊关节炎-脑炎病毒(CAEV)载体、牛免疫缺陷病毒(BIV)或修饰的牛免疫缺陷病毒(BIV)。
核酸
本文提供了编码用于本文所述的基因转移和表达技术中的本文公开的融合蛋白的核酸序列。虽然没有总是明确陈述，但是应当理解，本文提供的序列可以用于提供表达产物以及产生具有相同生物特性的蛋白质的基本上相同的序列。这些“生物等效的”或“生物活性的”或“等效的”多肽是由如本文所述的等效多核苷酸编码的。当使用在默认条件下运行的序列同一性方法比较时，它们可以具有与参考多肽至少60％、或可替代地至少65％、或可替代地至少70％、或可替代地至少75％、或可替代地至少80％、或可替代地至少85％、或可替代地至少90％、或可替代地至少95％、或可替代地至少98％相同的初级氨基酸序列。提供了特定多肽序列作为具体实施方案的例子。用具有类似电荷的可替代氨基酸对序列中的氨基酸进行修饰。另外，等效多核苷酸是在严格条件下与参考多核苷酸或其互补体杂交的多核苷酸，或者就多肽而言，是由在严格条件下与参考编码多核苷酸或其互补链杂交的多核苷酸编码的多肽。可替代地，等效多肽或蛋白质是从等效多核苷酸表达的多肽或蛋白质。
本文公开的核酸序列(例如，多核苷酸序列)可以是密码子优化的，密码子优化是本领域熟知的技术。在本文公开的一些实施方案中，示例性Cas序列(如例如，SEQ ID NO:46(Cas13d))被密码子优化以用于在人细胞中表达。密码子优化涉及以下事实，即不同细胞在对特定密码子的使用方面有所不同。该密码子偏倚对应于特定tRNA在细胞类型中的相对丰度的偏倚。通过改变序列中的密码子以与相应tRNA的相对丰度匹配，可能增加表达。还可能通过故意选择已知相应tRNA在特定细胞类型中罕见的密码子来减少表达。哺乳动物细胞以及多种其他生物的密码子使用表是本领域中已知的。基于遗传密码，可以产生编码例如Cas蛋白的核酸序列。在一些实施方案中，这样的序列被优化以用于在宿主细胞或靶细胞中表达，所述宿主细胞或靶细胞是如用于表达Cas蛋白的宿主细胞或在其中实践所公开方法的细胞(如在哺乳动物细胞例如人细胞中)。特定物种的密码子偏好和密码子使用表可以用于工程化编码Cas蛋白的分离的核酸分子(如编码与其相应野生型蛋白具有至少80％、至少85％、至少90％、至少92％、至少95％、至少96％、至少97％、至少98％、至少99％或100％序列同一性的蛋白质的核酸分子)，其利用该特定物种的密码子使用偏好。例如，本文公开的Cas蛋白可以被设计为具有特定目标生物优先使用的密码子。在一个例子中，Cas核酸序列被优化以用于在人细胞中表达，如与其相应野生型或起源核酸序列具有至少70％、至少80％、至少85％、至少90％、至少92％、至少95％、至少98％或至少99％序列同一性的Cas核酸序列。在一些实施方案中，编码至少一种Cas蛋白(其可能是载体的一部分)的分离的核酸分子包括被密码子优化以用于在真核细胞中表达的至少一个Cas蛋白编码序列或被密码子优化以用于在人细胞中表达的至少一个Cas蛋白编码序列。在一个实施方案中，这样的密码子优化的Cas编码序列与其相应野生型或起源序列具有至少80％、至少85％、至少90％、至少92％、至少95％、至少96％、至少97％、至少98％、至少99％或100％序列同一性。在另一个实施方案中，真核细胞密码子优化的核酸序列编码与其相应野生型或起源蛋白具有至少85％、至少90％、至少92％、至少95％、至少96％、至少97％、至少98％、至少99％或100％序列同一性的Cas蛋白。在另一个实施方案中，可以常规地产生含有功能等效核酸的多个克隆，所述功能等效核酸是如序列不同但编码相同Cas蛋白序列的核酸。编码序列中的沉默突变是由于遗传密码的简并性(即，冗余)所致，借此多于一种密码子可以编码相同氨基酸残基。因此，例如，亮氨酸可以由CTT、CTC、CTA、CTG、TTA或TTG编码；丝氨酸可以由TCT、TCC、TCA、TCG、AGT或AGC编码；天冬酰胺可以由AAT或AAC编码；天冬氨酸可以由GAT或GAC编码；半胱氨酸可以由TGT或TGC编码；丙氨酸可以由GCT、GCC、GCA或GCG编码；谷氨酰胺可以由CAA或CAG编码；酪氨酸可以由TAT或TAC编码；并且异亮氨酸可以由ATT、ATC或ATA编码。显示标准遗传密码的表格可以在多个来源发现(参见例如，Stryer,1988,Biochemistry,第3版,W.H.5Freemanand Co.,NY)。
“杂交”是指一种或多种多核苷酸反应形成通过核苷酸残基的碱基之间的氢键合稳定化的复合物的反应。氢键合可以通过Watson-Crick碱基配对、Hoogstein结合或以任何其他序列特异性方式来进行。所述复合物可以包含形成双链体结构的两条链、形成多链复合物的三条或更多条链、单条自杂交链或这些的任何组合。杂交反应可以构成更广泛过程(如PC反应的起始或核酶对多核苷酸的酶促切割)中的步骤。
严格杂交条件的例子包括：约25℃至约37℃的孵育温度；约6xSSC至约10x SSC的杂交缓冲液浓度；约0％至约25％的甲酰胺浓度；以及约4x SSC至约8x SSC的洗涤溶液。中等杂交条件的例子包括：约40℃至约50℃的孵育温度；约9x SSC至约2x SSC的缓冲液浓度；约30％至约50％的甲酰胺浓度；以及约5x SSC至约2x SSC的洗涤溶液。高严格性条件的例子包括：约55℃至约68℃的孵育温度；约lx SSC至约0.1x SSC的缓冲液浓度；约55％至约75％的甲酰胺浓度；以及约lx SSC、0.1x SSC或去离子水的洗涤溶液。通常，杂交孵育时间为5分钟至24小时，有1个、2个或更多个洗涤步骤，并且洗涤孵育时间为约1、2或15分钟。SSC是0.15M NaCl和15mM柠檬酸盐缓冲液。应理解，可以采用使用其他缓冲液系统的SSC的等效物。
“同源性”或“同一性”或“相似度”是指两个肽之间或两个核酸分子之间的序列相似度。同源性可以通过比较每个序列中的位置来确定，所述序列可以出于比较目的进行比对。在所比较序列中的位置由相同的碱基或氨基酸占据时，则所述分子在该位置是同源的。序列之间的同源性程度随着序列共有的匹配或同源位置的数量而变。“无关的”或“非同源的”序列与本发明的一个序列共有小于40％同一性、或可替代地小于25％同一性。
细胞
在本公开文本的组合物和方法的一些实施方案中，本公开文本的细胞是原核细胞。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的细胞是真核细胞。在一些实施方案中，所述细胞是哺乳动物细胞。在一些实施方案中，所述细胞是牛、鼠、猫、马、猪、犬、猿猴或人细胞。在一些实施方案中，所述细胞是非人哺乳动物细胞，如非人灵长类动物细胞。
在一些实施方案中，本公开文本的细胞是体细胞。在一些实施方案中，本公开文本的细胞是性细胞。在一些实施方案中，本公开文本的性细胞不是人细胞。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的细胞是干细胞。在一些实施方案中，本公开文本的细胞是胚胎干细胞。在一些实施方案中，本公开文本的胚胎干细胞不是人细胞。在一些实施方案中，本公开文本的细胞是多潜能干细胞或多能干细胞。在一些实施方案中，本公开文本的细胞是成体干细胞。在一些实施方案中，本公开文本的细胞是诱导多能干细胞(iPSC)。在一些实施方案中，本公开文本的细胞是造血干细胞(HSC)。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的体细胞是免疫细胞。在一些实施方案中，本公开文本的免疫细胞是淋巴细胞。在一些实施方案中，本公开文本的免疫细胞是T淋巴细胞(本文也称为T细胞)。本公开文本的示例性T细胞包括但不限于幼稚T细胞、效应T细胞、辅助T细胞、记忆T细胞、调节T细胞(Treg)和γδT细胞。在一些实施方案中，本公开文本的免疫细胞是B淋巴细胞。在一些实施方案中，本公开文本的免疫细胞是自然杀伤细胞。在一些实施方案中，本公开文本的免疫细胞是抗原呈递细胞。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的体细胞是肌肉细胞。在一些实施方案中，本公开文本的肌肉细胞是成肌细胞或肌细胞。在一些实施方案中，本公开文本的肌肉细胞是心肌细胞、骨骼肌细胞或平滑肌细胞。在一些实施方案中，本公开文本的肌肉细胞是横纹肌细胞。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的体细胞是上皮细胞。在一些实施方案中，本公开文本的上皮细胞形成鳞状细胞上皮、立方细胞上皮、柱状细胞上皮、层状细胞上皮、假复层柱状细胞上皮或移行细胞上皮。在一些实施方案中，本公开文本的上皮细胞形成腺体，包括但不限于松果腺、胸腺、垂体、甲状腺、肾上腺、顶质分泌腺、全质分泌腺、局质分泌腺、浆液腺、粘液腺和皮脂腺。在一些实施方案中，本公开文本的上皮细胞接触器官的外表面，所述器官包括但不限于肺、脾、胃、胰腺、膀胱、肠、肾、胆囊、肝、喉或咽。在一些实施方案中，本公开文本的上皮细胞接触血管或静脉的外表面。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的体细胞是神经元细胞。在一些实施方案中，本公开文本的神经元细胞是中枢神经系统的神经元。在一些实施方案中，本公开文本的神经元细胞是脑或脊髓的神经元。在一些实施方案中，本公开文本的神经元细胞是视网膜的神经元。在一些实施方案中，本公开文本的神经元细胞是脑神经或视神经的神经元。在一些实施方案中，本公开文本的神经元细胞是周围神经系统的神经元。在一些实施方案中，本公开文本的神经元细胞是神经胶质细胞或胶质细胞。在一些实施方案中，本公开文本的胶质细胞是中枢神经系统的胶质细胞，包括但不限于少突胶质细胞、星形胶质细胞、室管膜细胞和小胶质细胞。在一些实施方案中，本公开文本的胶质细胞是周围神经系统的胶质细胞，包括但不限于施万细胞和卫星细胞。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的体细胞是原代细胞。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的体细胞是培养的细胞。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的体细胞是体内的、体外的、离体的或原位的。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的体细胞是自体的或同种异体的。
使用方法
本公开文本提供了修饰本公开文本的RNA分子或由所述RNA分子编码的蛋白质的表达水平的方法，所述方法包括在适合于所述指导RNA或所述融合蛋白(或其部分)中的一种或多种与所述RNA分子结合的条件下使所述组合物与所述RNA分子接触。
本公开文本提供了修饰由RNA分子编码的蛋白质的活性的方法，所述方法包括在适合于所述指导RNA或所述融合蛋白(或其部分)中的一种或多种与所述RNA分子结合的条件下使所述组合物与所述RNA分子接触。
本公开文本提供了修饰本公开文本的RNA分子或由所述RNA分子编码的蛋白质的表达水平的方法，所述方法包括在适合于所述指导RNA或所述融合蛋白(或其部分)中的一种或多种与所述RNA分子结合的条件下使所述组合物与包含所述RNA分子的细胞接触。在一些实施方案中，所述细胞是体内的、体外的、离体的或原位的。在一些实施方案中，所述组合物包含载体，其包含含有本公开文本的指导RNA和本公开文本的融合蛋白的组合物。在一些实施方案中，所述载体是AAV。
本公开文本提供了修饰由RNA分子编码的蛋白质的活性的方法，所述方法包括在适合于所述指导RNA或所述融合蛋白(或其部分)中的一种或多种与所述RNA分子结合的条件下使所述组合物与包含所述RNA分子的细胞接触。在一些实施方案中，所述细胞是体内的、体外的、离体的或原位的。在一些实施方案中，所述组合物包含载体，其包含含有本公开文本的指导RNA或单一指导RNA和本公开文本的融合蛋白的组合物。在一些实施方案中，所述载体是AAV。
本公开文本提供了修饰本公开文本的RNA分子或由所述RNA分子编码的蛋白质的表达水平的方法，所述方法包括在适合于RNA核酸酶活性的条件下使所述组合物与所述RNA分子接触，其中所述融合蛋白诱导所述RNA分子中的断裂。
本公开文本提供了修饰由RNA分子编码的蛋白质的活性的方法，所述方法包括在适合于RNA核酸酶活性的条件下使所述组合物与所述RNA分子接触，其中所述融合蛋白诱导所述RNA分子中的断裂。
本公开文本提供了修饰本公开文本的RNA分子或由所述RNA分子编码的蛋白质的表达水平的方法，所述方法包括在适合于RNA核酸酶活性的条件下使所述组合物与包含所述RNA分子的细胞接触，其中所述融合蛋白诱导所述RNA分子中的断裂。在一些实施方案中，所述细胞是体内的、体外的、离体的或原位的。在一些实施方案中，所述组合物包含载体，其包含含有本公开文本的指导RNA和本公开文本的融合蛋白的组合物。在一些实施方案中，所述载体是AAV。
本公开文本提供了修饰由RNA分子编码的蛋白质的活性的方法，所述方法包括在适合于RNA核酸酶活性的条件下使所述组合物与包含所述RNA分子的细胞接触，其中所述融合蛋白诱导所述RNA分子中的断裂。在一些实施方案中，所述细胞是体内的、体外的、离体的或原位的。在一些实施方案中，所述组合物包含载体，其包含含有本公开文本的指导RNA或单一指导RNA和本公开文本的融合蛋白的组合物。在一些实施方案中，所述载体是AAV。
本公开文本提供了治疗疾病或障碍的方法，所述方法包括向受试者施用治疗有效量的本公开文本的组合物。
本公开文本提供了治疗疾病或障碍的方法，所述方法包括向受试者施用治疗有效量的本公开文本的组合物，其中所述组合物包含载体，所述载体包含含有本公开文本的指导RNA和本公开文本的融合蛋白的组合物，并且其中所述组合物修饰本公开文本的RNA分子或由所述RNA分子编码的蛋白质的表达水平。
本公开文本提供了治疗疾病或障碍的方法，所述方法包括向受试者施用治疗有效量的本公开文本的组合物，其中所述组合物包含载体，所述载体包含含有本公开文本的指导RNA和本公开文本的融合蛋白的组合物，并且其中所述组合物修饰由RNA分子编码的蛋白质的活性。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的疾病或障碍包括但不限于遗传疾病或障碍。在一些实施方案中，所述遗传疾病或障碍是单基因疾病或障碍。在一些实施方案中，所述单基因疾病或障碍是常染色体显性疾病或障碍、常染色体隐性疾病或障碍、X染色体连锁(X连锁)疾病或障碍、X连锁显性疾病或障碍、X连锁隐性疾病或障碍、Y连锁疾病或障碍或线粒体疾病或障碍。在一些实施方案中，所述遗传疾病或障碍是多基因疾病或障碍。在一些实施方案中，所述遗传疾病或障碍是多基因疾病或障碍。在一些实施方案中，所述单基因疾病或障碍是常染色体显性疾病或障碍，包括但不限于亨廷顿病(Huntington's disease)、神经纤维瘤病1型、神经纤维瘤病2型、马凡综合征(Marfansyndrome)、遗传性非息肉病性结直肠癌、遗传性多发性外生骨疣、血管性血友病(VonWillebrand disease)和急性间歇性卟啉病。在一些实施方案中，所述单基因疾病或障碍是常染色体隐性疾病或障碍，包括但不限于白化病、中链酰基辅酶A脱氢酶缺乏症、囊性纤维化、镰状细胞病、泰-萨克斯病(Tay-Sachs disease)、尼曼-皮克病(Niemann-Pickdisease)、脊髓性肌萎缩和罗伯茨综合征(Roberts syndrome)。在一些实施方案中，所述单基因疾病或障碍是X连锁疾病或障碍，包括但不限于肌营养不良、杜氏肌营养不良(Duchenne muscular dystrophy)、血友病、肾上腺脑白质营养不良(ALD)、雷特综合征(Rett syndrome)和血友病A。在一些实施方案中，所述单基因疾病或障碍是线粒体障碍，包括但不限于利伯氏遗传性视神经病变(Leber's hereditary optic neuropathy)。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的疾病或障碍包括但不限于免疫疾病或障碍。在一些实施方案中，所述免疫疾病或障碍是免疫缺陷疾病或障碍，包括但不限于B细胞缺乏症、T细胞缺乏症、嗜中性粒细胞减少症、无脾、补体缺乏症、获得性免疫缺陷综合征(AIDS)和由于医学干预所致的免疫缺陷(免疫抑制是医学疗法的预期或不利影响)。在一些实施方案中，所述免疫疾病或障碍是自身免疫性疾病或障碍，包括但不限于失弛缓症、艾迪生病(Addison’s disease)、成人斯蒂尔病(Adult Still'sdisease)、无丙种球蛋白血症、斑秃、淀粉样变性、抗GBM/抗TBM肾炎、抗磷脂综合征、自身免疫性血管性水肿、自身免疫性自主神经机能异常、自身免疫性脑脊髓炎、自身免疫性肝炎、自身免疫性内耳病(AIED)、自身免疫性心肌炎、自身免疫性卵巢炎、自身免疫性睾丸炎、自身免疫性胰腺炎、自身免疫性视网膜病变、自身免疫性荨麻疹、轴突和神经元神经病(AMAN)、巴洛病(Balódisease)、白塞病(Behcet's disease)、良性粘膜类天疱疮、大疱性类天疱疮、卡斯尔曼病(Castleman disease，CD)、乳糜泻、美洲锥虫病(Chagas disease)、慢性炎症性脱髓鞘性多发性神经病(CIDP)、慢性复发性多病灶性骨髓炎(CRMO)、变应性肉芽肿性血管炎(Churg-Strauss Syndrome，CSS)或嗜伊红细胞性肉芽肿病(EGPA)、瘢痕性类天疱疮、寇甘综合征(Cogan's syndrome)、冷凝集素病、先天性心脏传导阻滞、柯萨奇病毒性心肌炎、CREST综合征、克罗恩病(Crohn’s disease)、疱疹样皮炎、皮肌炎、德维克病(Devic's disease)(视神经脊髓炎)、盘状狼疮、德雷斯勒综合征(Dressler’s syndrome)、子宫内膜异位症、嗜酸性食道炎(EoE)、嗜酸性筋膜炎、结节性红斑、特发性混合性冷球蛋白血症(Essential mixed cryoglobulinemia)、伊文思综合征(Evans syndrome)、纤维肌痛、纤维化肺泡炎、巨细胞动脉炎(颞动脉炎)、巨细胞性心肌炎、肾小球肾炎、肺出血-肾炎综合征(Goodpasture’s syndrome)、肉芽肿性多血管炎、格雷夫斯病(Graves’disease)、格林-巴利综合征(Guillain-Barre syndrome)、桥本甲状腺炎(Hashimoto’s thyroiditis)、溶血性贫血、过敏性紫癜(Henoch-Schonlein purpura，HSP)、妊娠疱疹或妊娠性类天疱疮(PG)、化脓性汗腺炎(HS)(反常性痤疮)、低丙球蛋白血症、IgA肾病、IgG4相关性硬化性疾病、免疫性血小板减少性紫癜(ITP)、包涵体肌炎(IBM)、间质性膀胱炎(IC)、幼年型关节炎、幼年型糖尿病(1型糖尿病)、幼年型肌炎(JM)、川崎病(Kawasaki disease)、兰伯特-伊顿综合征(Lambert-Eaton syndrome)、白细胞破碎性血管炎、扁平苔癣、硬化性苔癣、木样结膜炎、线性IgA疾病(LAD)、狼疮、慢性莱姆病(Lyme disease chronic)、梅尼埃病(Meniere’sdisease)、显微镜下多血管炎(MPA)、混合性结缔组织病(MCTD)、蚕蚀性角膜溃疡(Mooren’sulcer)、穆-哈二氏病(Mucha-Habermann disease)、多灶性运动神经病(MMN)或MMNCB、多发性硬化症、重症肌无力、肌炎、发作性睡病、新生儿狼疮、视神经脊髓炎、嗜中性粒细胞减少症、眼部瘢痕性类天庖疮、视神经炎、复发性风湿病(PR)、PANDAS、副肿瘤性小脑变性(PCD)、阵发性睡眠性血红蛋白尿(PNH)、帕里-龙贝格综合征(Parry Romberg syndrome)、睫状体扁平部炎(周边葡萄膜炎)、帕-特二氏综合征(Parsonnage-Turner syndrome)、天疱疮、周围神经病变、静脉周围性脑脊髓炎(Perivenous encephalomyelitis)、恶性贫血(PA)、POEMS综合征、结节性多动脉炎、多腺体综合征I型、II型、III型、风湿性多肌痛、多发性肌炎、心肌梗死后综合征、心包切开术后综合征、原发性胆汁性肝硬化、原发性硬化性胆管炎、孕酮性皮炎、银屑病、银屑病关节炎、纯红细胞再生障碍(PRCA)、坏疽性脓皮病、雷诺现象(Raynaud’s phenomenon)、反应性关节炎、反射性交感神经营养不良、复发性多软骨炎、不宁腿综合征(RLS)、腹膜后纤维化、风湿热、类风湿性关节炎、结节病、施密特综合征(Schmidt syndrome)、巩膜炎、硬皮病、干燥综合征(
Figure BDA0002919433300001131
syndrome)、精子和睾丸自身免疫、僵人综合征(SPS)、亚急性细菌性心内膜炎(SBE)、苏萨克综合征(Susac'ssyndrome)、交感性眼炎(SO)、大动脉炎(Takayasu's arteritis)、颞动脉炎/巨细胞动脉炎、血小板减少性紫癜(TTP)、托洛萨-亨特综合征(Tolosa-Hunt syndrome，THS)、横贯性脊髓炎、1型糖尿病、溃疡性结肠炎(UC)、未分化结缔组织病(UCTD)、葡萄膜炎、血管炎、白癜风、小柳原田病(Vogt-Koyanagi-Harada Disease)或韦氏肉芽肿病(Wegener’sgranulomatosis)。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的疾病或障碍包括但不限于炎性疾病或障碍。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的疾病或障碍包括但不限于代谢性疾病或障碍。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的疾病或障碍包括但不限于退行性或进行性疾病或障碍。在一些实施方案中，所述退行性或进行性疾病或障碍包括但不限于肌萎缩侧索硬化(ALS)、亨廷顿病、阿尔茨海默病(Alzheimer’s disease)和衰老。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的疾病或障碍包括但不限于感染性疾病或障碍。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的疾病或障碍包括但不限于儿科或发育性疾病或障碍。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的疾病或障碍包括但不限于心血管疾病或障碍。
在本公开文本的组合物和方法的一些实施方案中，本公开文本的疾病或障碍包括但不限于增生性疾病或障碍。在一些实施方案中，所述增生性疾病或障碍是癌症。在一些实施方案中，所述癌症包括但不限于急性淋巴细胞性白血病(ALL)、急性髓性白血病(AML)、肾上腺皮质癌、AIDS相关性癌症、卡波西肉瘤(Kaposi Sarcoma)(软组织肉瘤)、AIDS相关性淋巴瘤(淋巴瘤)、原发性CNS淋巴瘤(淋巴瘤)、肛门癌、阑尾癌、胃肠道类癌瘤、星形细胞瘤、非典型畸胎瘤/横纹肌样瘤、中枢神经系统(脑癌)、基底细胞癌、胆管癌、膀胱癌、骨癌、尤因肉瘤(Ewing Sarcoma)、骨肉瘤、恶化纤维组织细胞瘤、脑瘤、乳腺癌、伯基特淋巴瘤(BurkittLymphoma)、类癌瘤、癌、心脏(Cardiac/Heart)肿瘤、胚胎瘤、胚细胞瘤、原发性CNS淋巴瘤、宫颈癌、胆管细胞癌(Cholangiocarcinoma)、脊索瘤、慢性淋巴细胞白血病(CLL)、慢性髓细胞性白血病(CML)、慢性骨髓增殖性肿瘤、结直肠癌、颅咽管瘤、皮肤T细胞淋巴瘤、原位导管癌、胚胎瘤、子宫内膜癌(子宫癌)、室管膜瘤、食管癌、鼻腔神经胶质瘤(头颈癌)、尤因肉瘤(骨癌)、颅外胚细胞瘤、性腺外胚细胞瘤、眼癌、儿童眼内黑色素瘤、眼内黑色素瘤、视网膜母细胞瘤、输卵管癌、骨恶性纤维组织细胞瘤和骨肉瘤、胆囊癌、胃(Gastric/Stomach)癌、胃肠道类癌瘤、胃肠道间质瘤(GIST)(软组织肉瘤)、儿童胃肠道间质瘤、胚细胞瘤、儿童颅外胚细胞瘤、性腺外胚细胞瘤、卵巢胚细胞瘤、睾丸癌、妊娠滋养细胞疾病、毛细胞白血病、头颈癌、心脏肿瘤、肝细胞(肝)癌、组织细胞增多症、霍奇金淋巴瘤(Hodgkin Lymphoma)、下咽癌(头颈癌)、眼内黑色素瘤、胰岛细胞瘤、胰腺神经内分泌肿瘤、卡波西肉瘤(软组织肉瘤)、肾(肾细胞)癌、朗格汉斯细胞组织细胞增生症(Langerhans Cell Histiocytosis)、喉癌(Laryngeal Cancer)(头颈癌)、白血病、唇和口腔癌(Lip and Oral Cavity Cancer)(头颈癌)、肝癌、肺癌(非小细胞和小细胞)、儿童肺癌、淋巴瘤、男性乳腺癌、骨恶性纤维组织细胞瘤和骨肉瘤、黑色素瘤、梅克尔细胞癌(Merkel Cell Carcinoma)(皮肤癌)、间皮瘤、隐匿性原发性转移性鳞状颈癌(头颈癌)、具有NUT基因变化的中线道癌、口腔癌(Mouth Cancer)(头颈癌)、多发性内分泌肿瘤综合征、多发性骨髓瘤/浆细胞瘤、蕈样真菌病(淋巴瘤)、骨髓增生异常综合征、骨髓增生异常性/骨髓增生性肿瘤、鼻腔和鼻旁窦癌(头颈癌)、鼻咽癌(头颈癌)、神经母细胞瘤、非霍奇金淋巴瘤、非小细胞肺癌、口腔癌(Oral Cancer)、唇和口腔癌和口咽癌、骨肉瘤和骨恶性纤维组织细胞瘤、卵巢癌、胰腺癌、胰腺神经内分泌肿瘤(胰岛细胞瘤)、乳头状瘤病、副神经节瘤、甲状旁腺癌、阴茎癌、咽癌(头颈癌)、嗜铬细胞瘤、浆细胞瘤/多发性骨髓瘤、胸膜肺母细胞瘤、妊娠期乳腺癌、原发性中枢神经系统(CNS)淋巴瘤、原发性腹膜癌、前列腺癌、直肠癌、复发性癌症、肾细胞(肾)癌、视网膜母细胞瘤、横纹肌肉瘤、儿童(软组织肉瘤)、涎腺癌(头颈癌)、肉瘤、儿童横纹肌肉瘤(软组织肉瘤)、儿童血管瘤(软组织肉瘤)、尤因肉瘤(骨癌)、卡波西肉瘤(软组织肉瘤)、骨肉瘤(骨癌)、子宫肉瘤、塞扎里综合征(Sézary Syndrome)、淋巴瘤、皮肤癌、小细胞肺癌、小肠癌、软组织肉瘤、皮肤鳞状细胞癌、鳞状颈癌、胃(Stomach/Gastric)癌、T细胞淋巴瘤、睾丸癌、喉癌(Throat Cancer)(头颈癌)、鼻咽癌、口咽癌、下咽癌、胸腺瘤和胸腺癌、甲状腺癌、肾盂和输尿管移行细胞癌、肾细胞癌、尿道癌、子宫肉瘤、阴道癌、血管瘤(软组织肉瘤)、外阴癌、肾母细胞瘤(WilmsTumor)和其他儿童肾脏肿瘤。
在本公开文本的方法的一些实施方案中，本公开文本的受试者已经被诊断患有所述疾病或障碍。在一些实施方案中，本公开文本的受试者呈现所述疾病或障碍的至少一种体征或症状。在一些实施方案中，所述受试者具有预示患上所述疾病或障碍的风险的生物标记。在一些实施方案中，所述生物标记是基因突变。
在本公开文本的方法的一些实施方案中，本公开文本的受试者是雌性。在本公开文本的方法的一些实施方案中，本公开文本的受试者是雄性。在一些实施方案中，本公开文本的受试者具有两个XX或XY染色体。在一些实施方案中，本公开文本的受试者具有两个XX或XY染色体和第三染色体(X或Y)。
在本公开文本的方法的一些实施方案中，本公开文本的受试者是新生儿、婴儿、儿童、成人、年长成人或老年人。在本公开文本的方法的一些实施方案中，本公开文本的受试者为至少1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30或31日龄。在本公开文本的方法的一些实施方案中，本公开文本的受试者为至少1、2、3、4、5、6、7、8、9、10、11或12月龄。在本公开文本的方法的一些实施方案中，本公开文本的受试者为至少1、2、3、4、5、6、7、8、9、10、15、20、25、30、35、40、45、50、55、60、65、70、75、80、85、90、95、100岁或之间的任何岁数或非整岁数。
在本公开文本的方法的一些实施方案中，本公开文本的受试者是哺乳动物。在一些实施方案中，本公开文本的受试者是非人哺乳动物。
在本公开文本的方法的一些实施方案中，本公开文本的受试者是人。
在本公开文本的方法的一些实施方案中，治疗有效量包含本公开文本的组合物的单个剂量。在一些实施方案中，治疗有效量包含治疗有效量包含本公开文本的组合物的至少一个剂量。在一些实施方案中，治疗有效量包含治疗有效量包含本公开文本的组合物的一个或多个剂量。
在本公开文本的方法的一些实施方案中，治疗有效量消除所述疾病或障碍的体征或症状。在一些实施方案中，治疗有效量降低所述疾病或障碍的体征或症状的严重程度。
在本公开文本的方法的一些实施方案中，治疗有效量消除所述疾病或障碍。
在本公开文本的方法的一些实施方案中，治疗有效量预防疾病或障碍的发作。在一些实施方案中，治疗有效量延迟疾病或障碍的发作。在一些实施方案中，治疗有效量降低所述疾病或障碍的体征或症状的严重程度。在一些实施方案中，治疗有效量改善所述受试者的预后。
在本公开文本的方法的一些实施方案中，将本公开文本的组合物全身施用至所述受试者。在一些实施方案中，将本公开文本的组合物通过静脉内途径施用至所述受试者。在一些实施方案中，将本公开文本的组合物通过注射或输注施用至所述受试者。
在本公开文本的方法的一些实施方案中，将本公开文本的组合物局部施用至所述受试者。在一些实施方案中，将本公开文本的组合物通过骨内、眼内、脑脊髓内或脊柱内途径施用至所述受试者。在一些实施方案中，将本公开文本的组合物直接施用至中枢神经系统的脑脊液。在一些实施方案中，将本公开文本的组合物直接施用至眼组织或流体，并且在眼结构外不具有生物利用性。在一些实施方案中，将本公开文本的组合物通过注射或输注施用至所述受试者。
在一些实施方案中，将包含本文公开的RNA结合融合蛋白的组合物配制为药物组合物。简言之，如本文所公开使用的药物组合物可以包含与一种或多种药学上或生理上可接受的载体、稀释剂或赋形剂组合的一种或多种融合蛋白或编码所述一种或多种融合蛋白的多核苷酸，所述融合蛋白或多核苷酸任选地包含于AAV中，所述AAV任选地也是免疫正交的。此类组合物可以包含缓冲液，如中性缓冲盐水、磷酸盐缓冲盐水等；碳水化合物，如葡萄糖、甘露糖、蔗糖或葡聚糖、甘露醇；蛋白质；多肽或氨基酸，如甘氨酸；抗氧化剂；螯合剂，如EDTA或谷胱甘肽；佐剂(例如，氢氧化铝)；和防腐剂。可以将本公开文本的组合物配制用于口服、静脉内、局部、肠内、眼内和/或肠胃外施用。在某些实施方案中，将本公开文本的组合物配制用于静脉内施用。
示例实施方案：
实施方案1.一种组合物，其包含：
(a)包含特异性结合RNA分子内的靶序列的指导RNA(gRNA)的序列，以及
(b)编码融合蛋白的序列，所述序列包含编码第一RNA结合多肽的序列和编码第二RNA结合多肽的序列，
其中所述第一RNA结合多肽和所述第二RNA结合多肽都不包含显著DNA-核酸酶活性，
其中所述第一RNA结合多肽与所述第二RNA结合多肽不相同，并且
其中所述第二RNA结合多肽包含RNA-核酸酶活性；
或者
一种组合物，其包含编码融合蛋白的核酸序列，所述融合蛋白包含第一RNA结合多肽和第二RNA结合多肽，其中所述第一RNA结合多肽不是指导的RNA结合多肽，其中所述第一RNA结合多肽与所述第二RNA结合多肽不相同，并且其中所述第二RNA结合多肽包含RNA-核酸酶活性。
实施方案2.根据实施方案1所述的组合物，其中所述靶序列包含至少一个重复的序列。
实施方案3.根据实施方案1或2所述的组合物，其中包含所述gRNA的序列包含能够在真核细胞中表达所述gRNA的启动子。
实施方案4.根据实施方案3所述的组合物，其中所述真核细胞是动物细胞。
实施方案5.根据实施方案4所述的组合物，其中所述动物细胞是哺乳动物细胞。
实施方案6.根据实施方案5所述的组合物，其中所述动物细胞是人细胞。
实施方案7.根据实施方案1-6中任一项所述的组合物，其中所述启动子是组成型活性启动子。
实施方案8.根据实施方案1-7中任一项所述的组合物，其中所述启动子是从能够驱动RNA聚合酶的表达的启动子分离或衍生的。
实施方案9.根据实施方案8所述的组合物，其中所述启动子是从U6启动子分离或衍生的。
实施方案10.根据实施方案1-7中任一项所述的组合物，其中所述启动子是从能够驱动转移RNA(tRNA)的表达的启动子分离或衍生的。
实施方案11.根据实施方案10所述的组合物，其中所述启动子是从以下启动子分离或衍生的：丙氨酸tRNA启动子、精氨酸tRNA启动子、天冬酰胺tRNA启动子、天冬氨酸tRNA启动子、半胱氨酸tRNA启动子、谷氨酰胺tRNA启动子、谷氨酸tRNA启动子、甘氨酸tRNA启动子、组氨酸tRNA启动子、异亮氨酸tRNA启动子、亮氨酸tRNA启动子、赖氨酸tRNA启动子、甲硫氨酸tRNA启动子、苯丙氨酸tRNA启动子、脯氨酸tRNA启动子、丝氨酸tRNA启动子、苏氨酸tRNA启动子、色氨酸tRNA启动子、酪氨酸tRNA启动子或缬氨酸tRNA启动子。
实施方案12.根据实施方案10所述的组合物，其中所述启动子是从缬氨酸tRNA启动子分离或衍生的。
实施方案13.根据实施方案1-12中任一项所述的组合物，其中包含所述gRNA的序列包含与所述靶RNA序列特异性结合的间隔子序列。
实施方案14.根据实施方案13所述的组合物，其中所述间隔子序列与所述靶RNA序列具有至少50％、55％、60％、65％、70％、75％、80％、87％、90％、95％、97％、99％或之间的任何百分比的互补性。
实施方案15.根据实施方案13所述的组合物，其中所述间隔子序列与所述靶RNA序列具有100％互补性。
实施方案16.根据实施方案13-15中任一项所述的组合物，其中所述间隔子序列包含20个核苷酸或由其组成。
实施方案17.根据实施方案13-15中任一项所述的组合物，其中所述间隔子序列包含21个核苷酸或由其组成。
实施方案18.根据实施方案17所述的组合物，其中所述间隔子序列包含序列UGGAGCGAGCAUCCCCCAAA(SEQ ID NO:1)、GUUUGGGGGAUGCUCGCUCCA(SEQ ID NO:2)、CCCUCACUGCUGGGGAGUCC(SEQ ID NO:3)、GGACUCCCCAGCAGUGAGGG(SEQ ID NO:4)、GCAACUGGAUCAAUUUGCUG(SEQ ID NO:5)、GCAGCAAAUUGAUCCAGUUGC(SEQ ID NO:6)、GCAUUCUUAUCUGGUCAGUGC(SEQ ID NO:7)、GCACUGACCAGAUAAGAAUG(SEQ ID NO:8)、GAGCAGCAGCAGCAGCAGCAG(SEQ ID NO:9)、GCAGGCAGGCAGGCAGGCAGG(SEQ ID NO:10)、GCCCCGGCCCCGGCCCCGGC(SEQ ID NO:11)、或GCTGCTGCTGCTGCTGCTGC(SEQ ID NO:12)、GGGGCCGGGGCCGGGGCCGG(SEQ ID NO:74)、GGGCCGGGGCCGGGGCCGGG(SEQ ID NO:75)、GGCCGGGGCCGGGGCCGGGG(SEQ ID NO:76)、GCCGGGGCCGGGGCCGGGGC(SEQ ID NO:77)、CCGGGGCCGGGGCCGGGGCC(SEQ ID NO:78)、CGGGGCCGGGGCCGGGGCCG(SEQ ID NO:79)。
实施方案19.根据实施方案1-18中任一项所述的组合物，其中包含所述gRNA的序列包含与所述第一RNA结合蛋白特异性结合的支架序列。
实施方案20.根据实施方案19所述的组合物，其中所述支架序列包含茎环结构。
实施方案21.根据实施方案19或20所述的组合物，其中所述支架序列包含90个核苷酸或由其组成。
实施方案22.根据实施方案19或20所述的组合物，其中所述支架序列包含93个核苷酸或由其组成。
实施方案23.根据实施方案22所述的组合物，其中所述支架序列包含序列
GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUUU(SEQ ID NO:13)。
实施方案24.根据实施方案16所述的组合物，其中所述间隔子序列包含序列GUGAUAAGUGGAAUGCCAUG(SEQ ID NO:14)、CUGGUGAACUUCCGAUAGUG(SEQ ID NO:15)或GAGATATAGCCTGGTGGTTC(SEQ ID NO:16)。
实施方案25.根据实施方案19或24所述的组合物，其中所述支架序列包含茎环结构。
实施方案26.根据实施方案25所述的组合物，其中所述支架序列包含85个核苷酸或由其组成。
实施方案27.根据实施方案26所述的组合物，其中所述支架序列包含序列
GGACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUU(SEQ ID NO:17)。
实施方案28.根据实施方案16所述的组合物，其中所述间隔子序列包含以下序列：序列CUG(SEQ ID NO:18)、CCUG(SEQ ID NO:19)、CAG(SEQ ID NO:80)、GGGGCC(SEQ ID NO:81)或其任何组合的至少1、2、3、4、5、6或7个重复。
实施方案29.根据实施方案28所述的组合物，其中包含所述gRNA的序列包含与所述第一RNA结合蛋白特异性结合的支架序列。
实施方案30.根据实施方案29所述的组合物，其中所述支架序列包含茎环结构。
实施方案31.根据实施方案29或30所述的组合物，其中所述支架序列包含90个核苷酸或由其组成。
实施方案32.根据实施方案30或31所述的组合物，其中所述支架序列包含93个核苷酸或由其组成。
实施方案33.根据实施方案32所述的组合物，其中所述支架序列包含序列
GUUUAAGAGCUAUGCUGGAAACAGCAUAGCAAGUUUAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUUU(SEQ ID NO:82)或GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUUU(SEQ ID NO:83)。
实施方案34.根据实施方案1-33中任一项所述的组合物，其中所述gRNA不结合或不选择性结合所述RNA分子内的第二序列。
实施方案35.根据实施方案34所述的组合物，其中RNA基因组或RNA转录组包含所述RNA分子。
实施方案36.根据实施方案1-35中任一项所述的组合物，其中所述第一RNA结合蛋白包含CRISPR-Cas蛋白。
实施方案37.根据实施方案36所述的组合物，其中所述CRISPR-Cas蛋白是II型CRISPR-Cas蛋白。
实施方案38.根据实施方案37所述的组合物，其中所述第一RNA结合蛋白包含Cas9多肽或其RNA结合部分。
实施方案39.根据实施方案36所述的组合物，其中所述CRISPR-Cas蛋白是V型CRISPR-Cas蛋白。
实施方案40.根据实施方案39所述的组合物，其中所述第一RNA结合蛋白包含Cpf1多肽或其RNA结合部分。
实施方案41.根据实施方案36所述的组合物，其中所述CRISPR-Cas蛋白是VI型CRISPR-Cas蛋白。
实施方案42.根据实施方案41所述的组合物，其中所述第一RNA结合蛋白包含Cas13多肽或其RNA结合部分。
实施方案43.根据实施方案36-42中任一项所述的组合物，其中所述CRISPR-Cas蛋白包含天然RNA核酸酶活性。
实施方案44.根据实施方案43所述的组合物，其中所述天然RNA核酸酶活性被降低或抑制。
实施方案45.根据实施方案43所述的组合物，其中所述天然RNA核酸酶活性被增加或诱导。
实施方案46.根据实施方案36-45中任一项所述的组合物，其中所述CRISPR-Cas蛋白包含天然DNA核酸酶活性，并且其中所述天然DNA核酸酶活性被抑制。
实施方案47.根据实施方案46所述的组合物，其中所述CRISPR-Cas蛋白包含突变。
实施方案48.根据实施方案47所述的组合物，其中所述CRISPR-Cas蛋白的核酸酶结构域包含所述突变。
实施方案49.根据实施方案47所述的组合物，其中所述突变发生在编码所述CRISPR-Cas蛋白的核酸中。
实施方案50.根据实施方案47所述的组合物，其中所述突变发生在编码所述CRISPR-Cas蛋白的氨基酸中。
实施方案51.根据实施方案47-50中任一项所述的组合物，其中所述突变包含取代、插入、缺失、移码、倒位或转座。
实施方案52.根据实施方案47-50中任一项所述的组合物，其中所述突变包含核酸酶结构域、所述核酸酶结构域内的结合位点、所述核酸酶结构域内的活性位点或所述核酸酶结构域内的至少一个必需氨基酸残基的缺失。
实施方案53.根据实施方案1-35中任一项所述的组合物，其中所述第一RNA结合蛋白包含Pumilio和FBF(PUF)蛋白。
实施方案54.根据实施方案53所述的组合物，其中所述第一RNA结合蛋白包含基于Pumilio的联合体(PUMBY)蛋白。
实施方案55.根据实施方案1-54中任一项所述的组合物，其中所述第一RNA结合蛋白不需要多聚化以用于RNA结合活性。
实施方案56.根据实施方案55所述的组合物，其中所述第一RNA结合蛋白不是多聚体复合物的单体。
实施方案57.根据实施方案55所述的组合物，其中多聚体蛋白复合物不包含所述第一RNA结合蛋白。
实施方案58.根据实施方案1-57中任一项所述的组合物，其中所述第一RNA结合蛋白与所述RNA分子内的靶序列选择性结合。
实施方案59.根据实施方案58所述的组合物，其中所述第一RNA结合蛋白不包含对所述RNA分子内的第二序列的亲和力。
实施方案60.根据实施方案58或59所述的组合物，其中所述第一RNA结合蛋白不包含对所述RNA分子内的第二序列的高亲和力或不选择性结合所述第二序列。
实施方案61.根据实施方案60所述的组合物，其中RNA基因组或RNA转录组包含所述RNA分子。
实施方案62.根据实施方案1-61中任一项所述的组合物，其中所述第一RNA结合蛋白包含在2个与1300个之间的氨基酸，包括端点。
实施方案63.根据实施方案1-62中任一项所述的组合物，其中编码所述第一RNA结合蛋白的序列还包含编码核定位信号(NLS)的序列。
实施方案64.根据实施方案63所述的组合物，其中编码核定位信号(NLS)的所述序列定位于编码所述第一RNA结合蛋白的序列的3'。
实施方案65.根据实施方案64所述的组合物，其中所述第一RNA结合蛋白包含在所述蛋白质的C末端的NLS。
实施方案66.根据实施方案1-62中任一项所述的组合物，其中编码所述第一RNA结合蛋白的序列还包含编码第一NLS的第一序列和编码第二NLS的第二序列。
实施方案67.根据实施方案66所述的组合物，其中编码所述第一NLS或所述第二NLS的序列定位于编码所述第一RNA结合蛋白的序列的3'。
实施方案68.根据实施方案67所述的组合物，其中所述第一RNA结合蛋白包含在所述蛋白质的C末端的所述第一NLS或所述第二NLS。
实施方案69.根据实施方案1-68中任一项所述的组合物，其中所述第二RNA结合蛋白包含核酸酶结构域或由其组成。
实施方案70.根据实施方案69所述的组合物，其中编码所述第二RNA结合蛋白的序列包含RNA酶或由其组成。
实施方案71.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶1或由其组成。
实施方案72.根据实施方案71所述的组合物，其中所述RNA酶1蛋白包含SEQ IDNO:20或由其组成。
实施方案73.根据实施方案72所述的组合物，其中所述第二RNA结合蛋白包含RNA酶4或由其组成。
实施方案74.根据实施方案73所述的组合物，其中所述RNA酶4蛋白包含SEQ IDNO:21或由其组成。
实施方案75.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶6或由其组成。
实施方案76.根据实施方案75所述的组合物，其中所述RNA酶6蛋白包含SEQ IDNO:22或由其组成。
实施方案77.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶7或由其组成。
实施方案78.根据实施方案77所述的组合物，其中所述RNA酶7蛋白包含SEQ IDNO:23或由其组成。
实施方案79.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶8或由其组成。
实施方案80.根据实施方案79所述的组合物，其中所述RNA酶8蛋白包含SEQ IDNO:24或由其组成。
实施方案81.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶2或由其组成。
实施方案82.根据实施方案81所述的组合物，其中所述RNA酶2蛋白包含SEQ IDNO:25或由其组成。
实施方案83.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶6PL或由其组成。
实施方案84.根据实施方案83所述的组合物，其中所述RNA酶6PL蛋白包含SEQ IDNO:26或由其组成。
实施方案85.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶L或由其组成。
实施方案86.根据实施方案85所述的组合物，其中所述RNA酶L蛋白包含SEQ IDNO:27或由其组成。
实施方案87.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶T2或由其组成。
实施方案88.根据实施方案87所述的组合物，其中所述RNA酶T2蛋白包含SEQ IDNO:28或由其组成。
实施方案89.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶11或由其组成。
实施方案90.根据实施方案89所述的组合物，其中所述RNA酶11包含SEQ ID NO:29或由其组成。
实施方案91.根据实施方案70所述的组合物，其中所述第二RNA结合蛋白包含RNA酶T2样蛋白或由其组成。
实施方案92.根据实施方案91所述的组合物，其中所述RNA酶T2样蛋白包含SEQ IDNO:30或由其组成。
实施方案93.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含NOB1多肽或由其组成。
实施方案94.根据实施方案93所述的组合物，其中所述NOB1多肽包含SEQ ID NO:31或由其组成。
实施方案95.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含内切核酸酶或由其组成。
实施方案96.根据实施方案95所述的组合物，其中所述第二RNA结合蛋白包含内切核酸酶V(ENDOV)或由其组成。
实施方案97.根据实施方案96所述的组合物，其中所述ENDOV蛋白包含SEQ ID NO:32或由其组成。
实施方案98.根据实施方案95所述的组合物，其中所述第二RNA结合蛋白包含内切核酸酶G(ENDOG)或由其组成。
实施方案99.根据实施方案98所述的组合物，其中所述ENDOG蛋白包含SEQ ID NO:33或由其组成。
实施方案100.根据实施方案95所述的组合物，其中所述第二RNA结合蛋白包含内切核酸酶D1(ENDOD1)或由其组成。
实施方案101.根据实施方案100所述的组合物，其中所述ENDOD1蛋白包含SEQ IDNO:34或由其组成。
实施方案102.根据实施方案95所述的组合物，其中所述第二RNA结合蛋白包含人瓣状内切核酸酶-1(hFEN1)或由其组成。
实施方案103.根据实施方案102所述的组合物，其中所述hFEN1蛋白包含SEQ IDNO:35或由其组成。
实施方案104.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含人斯库拉芬蛋白14(hSLFN14)多肽或由其组成。
实施方案105.根据实施方案104所述的组合物，其中所述hSLFN14多肽包含SEQ IDNO:36或由其组成。
实施方案106.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含人β-内酰胺酶样蛋白2(hLACTB2)多肽或由其组成。
实施方案107.根据实施方案106所述的组合物，其中所述hLACTB2多肽包含SEQ IDNO:37或由其组成。
实施方案108.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含无嘌呤/无嘧啶(AP)内切脱氧核糖核酸酶(APEX2)多肽或由其组成。
实施方案109.根据实施方案108所述的组合物，其中所述APEX2多肽包含SEQ IDNO:38或由其组成。
实施方案110.根据实施方案108所述的组合物，其中所述APEX2多肽包含SEQ IDNO:39或由其组成。
实施方案111.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含血管生成素(ANG)多肽或由其组成。
实施方案112.根据实施方案111所述的组合物，其中所述ANG多肽包含SEQ ID NO:40或由其组成。
实施方案113.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含热反应蛋白12(HRSP12)多肽或由其组成。
实施方案114.根据实施方案113所述的组合物，其中所述HRSP12多肽包含SEQ IDNO:41或由其组成。
实施方案115.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含含锌指CCCH型12A(ZC3H12A)多肽或由其组成。
实施方案116.根据实施方案115所述的组合物，其中所述ZC3H12A多肽包含SEQ IDNO:42或由其组成。
实施方案117.根据实施方案115所述的组合物，其中所述ZC3H12A多肽包含SEQ IDNO:43或由其组成。
实施方案118.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含反应性中间亚胺脱氨酶A(RIDA)多肽或由其组成。
实施方案119.根据实施方案118所述的组合物，其中所述RIDA多肽包含SEQ IDNO:44或由其组成。
实施方案120.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含磷脂酶D家族成员6(PDL6)多肽或由其组成。
实施方案121.根据实施方案120所述的组合物，其中所述PDL6多肽包含SEQ IDNO:126或由其组成。
实施方案122.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含内切核酸酶III样蛋白1(NTHL)多肽或由其组成。
实施方案123.根据实施方案122所述的组合物，其中所述NTHL多肽包含SEQ IDNO:123或由其组成。
实施方案124.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含线粒体核糖核酸酶P催化亚基(KIAA0391)多肽或由其组成。
实施方案125.根据实施方案124所述的组合物，其中所述KIAA0391多肽包含SEQID NO:127或由其组成。
实施方案126.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含无嘌呤或无嘧啶位点裂解酶(APEX1)多肽或由其组成。
实施方案127.根据实施方案126所述的组合物，其中所述APEX1多肽包含SEQ IDNO:125或由其组成。
实施方案128.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含阿尔古蛋白2(AGO2)多肽或由其组成。
实施方案129.根据实施方案128所述的组合物，其中所述AGO2多肽包含SEQ IDNO:128或由其组成。
实施方案130.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含线粒体核酸酶EXOG(EXOG)多肽或由其组成。
实施方案131.根据实施方案130所述的组合物，其中所述EXOG多肽包含SEQ IDNO:129或由其组成。
实施方案132.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含含锌指CCCH型12D(ZC3H12D)多肽或由其组成。
实施方案133.根据实施方案132所述的组合物，其中所述ZC3H12D多肽包含SEQ IDNO:130或由其组成。
实施方案134.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含内质网核信号转导蛋白2(ERN2)多肽或由其组成。
实施方案135.根据实施方案134所述的组合物，其中所述ERN2多肽包含SEQ IDNO:131或由其组成。
实施方案136.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含回力球mRNA监督和核糖体挽救因子(PELO)多肽或由其组成。
实施方案137.根据实施方案136所述的组合物，其中所述PELO多肽包含SEQ IDNO:132或由其组成。
实施方案138.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含YBEY金属肽酶(YBEY)多肽或由其组成。
实施方案139.根据实施方案138所述的组合物，其中所述YBEY多肽包含SEQ IDNO:133或由其组成。
实施方案140.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含剪切和多聚腺苷酸化特异性因子4样蛋白(CPSF4L)多肽或由其组成。
实施方案141.根据实施方案140所述的组合物，其中所述CPSF4L包含SEQ ID NO:134或由其组成。
实施方案142.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含hCG_2002731多肽或由其组成。
实施方案143.根据实施方案142所述的组合物，其中所述hCG_2002731多肽包含SEQ ID NO:135或由其组成。
实施方案144.根据实施方案142所述的组合物，其中所述hCG_2002731多肽包含SEQ ID NO:136或由其组成。
实施方案145.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含切除修复交叉互补组1(ERCC1)多肽或由其组成。
实施方案146.根据实施方案145所述的组合物，其中所述ERCC1多肽包含SEQ IDNO:137或由其组成。
实施方案147.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含ras相关C3肉毒杆菌毒素底物1亚型(RAC1)多肽或由其组成。
实施方案148.根据实施方案147所述的组合物，其中所述RAC1多肽包含SEQ IDNO:138或由其组成。
实施方案149.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含核糖核酸酶A A1(RAA1)多肽或由其组成。
实施方案150.根据实施方案149所述的组合物，其中所述RAA1多肽包含SEQ IDNO:139或由其组成。
实施方案151.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含Ras相关蛋白(RAB1)多肽或由其组成。
实施方案152.根据实施方案151所述的组合物，其中所述RAB1多肽包含SEQ IDNO:140或由其组成。
实施方案153.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含DNA复制解旋酶/核酸酶2(DNA2)多肽或由其组成。
实施方案154.根据实施方案153所述的组合物，其中所述DNA2多肽包含SEQ IDNO:141或由其组成。
实施方案155.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含FLJ35220多肽或由其组成。
实施方案156.根据实施方案155所述的组合物，其中所述FLJ35220多肽包含SEQID NO:142或由其组成。
实施方案157.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含FLJ13173多肽或由其组成。
实施方案158.根据实施方案157所述的组合物，其中所述FLJ13173多肽包含SEQID NO:143或由其组成。
实施方案159.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含DNA修复内切核酸酶XPF(ERCC4)多肽或由其组成。
实施方案160.根据实施方案159所述的组合物，其中所述ERCC4多肽包含SEQ IDNO:64或由其组成。
实施方案161.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(K41R))多肽或由其组成。
实施方案162.根据实施方案161所述的组合物，其中所述RNA酶1(K41R)多肽包含SEQ ID NO:116或由其组成。
实施方案163.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(K41R、D121E))多肽或由其组成。
实施方案164.根据实施方案163所述的组合物，其中所述RNA酶1(RNA酶1(K41R、D121E))多肽包含SEQ ID NO:117或由其组成。
实施方案165.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(K41R、D121E、H119N))多肽或由其组成。
实施方案166.根据实施方案165所述的组合物，其中所述RNA酶1(RNA酶1(K41R、D121E、H119N))多肽包含SEQ ID NO:118或由其组成。
实施方案167.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(H119N))多肽或由其组成。
实施方案168.根据实施方案167所述的组合物，其中所述RNA酶1(RNA酶1(H119N))多肽包含SEQ ID NO:119或由其组成。
实施方案169.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽或由其组成。
实施方案170.根据实施方案169所述的组合物，其中所述RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽包含SEQ ID NO:120或由其组成。
实施方案171.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽或由其组成。
实施方案172.根据实施方案171所述的组合物，其中所述RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N、K41R、D121E))多肽包含SEQ ID NO:121或由其组成。
实施方案173.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含突变的RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N))多肽或由其组成。
实施方案174.根据实施方案173所述的组合物，其中所述RNA酶1(RNA酶1(R39D、N67D、N88A、G89D、R91D))多肽包含SEQ ID NO:122或由其组成。
实施方案175.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含特诺伊林跨膜蛋白1(TENM1)多肽或由其组成。
实施方案176.根据实施方案175所述的组合物，其中所述TENM1多肽包含SEQ IDNO:144或由其组成。
实施方案177.根据实施方案69所述的组合物，其中所述第二RNA结合蛋白包含特诺伊林跨膜蛋白2(TENM2)多肽或由其组成。
实施方案178.根据实施方案177所述的组合物，其中所述TENM2多肽包含SEQ IDNO:145或由其组成。
实施方案179.一种组合物，所述组合物包含编码靶RNA结合融合蛋白的序列，所述序列包含(a)编码第一RNA结合多肽或其部分的序列；以及(b)编码第二RNA结合多肽的序列，其中所述第一RNA结合多肽结合并非由gRNA序列指导的靶RNA，并且其中所述第二RNA结合多肽包含RNA-核酸酶活性。
实施方案180.根据实施方案179所述的组合物，其中所述第一RNA结合多肽或其部分是PUF、PUMBY或PPR多肽或其部分。
实施方案181.一种用于修饰RNA分子或由所述RNA分子编码的蛋白质的表达水平的方法，所述方法包括在适合于融合蛋白或其部分与所述RNA分子结合的条件下使根据实施方案1或179所述的组合物与所述RNA分子接触。
实施例
实施例1：方法
将HEK-293细胞在含有10％FBS和1％青霉素/链霉素的DMEM(GIBCO)中培养，并以90％-100％汇合度进行传代。将细胞以1x 10^5个细胞/孔接种于24孔板中用于RNA分离，或以.5x 10^5个细胞/孔接种于96孔板中用于萤光素酶测定。RNA分离是用RNAeasy柱(Qiagen)根据制造商的方案来进行。使用Nanodrop分光光度计来估计RNA质量和浓度。使用Superscript III(Thermo)以随机引物根据制造商的方案进行cDNA制备。以与报告基因质粒中的CTG重复相邻的序列中的引物使用以下引物来进行qPCR：
正向引物 TetCTG_DMPK_E15_F TCGGAGCGGTTGTGAACT SEQ ID NO:83
反向引物 TetCTG_DMPK_E15_R GTTCGCCGTTGTTCTGTC SEQ ID NO:84
通过针对GAPDH进行归一化来确定CTG重复报告基因的相对丰度。接下来，将靶向CTG的sgRNA的水平针对非靶向sgRNA进行归一化，以产生在相关数据包中报告的最终值。
Figure BDA0002919433300001321
用Promega双重萤光素酶试剂盒根据制造商的说明进行萤光素酶测定。所报告的值是萤火虫与海肾萤光素酶发光读数的比率。
实施例2：重复性RNA分子和mRNA分子的RNA指导的切割
实验设计：构建具有注释的RNA内切核酸酶活性的人蛋白与Cas9(酿脓链球菌或空肠弯曲杆菌)的各种融合物。将编码上文融合物的质粒与含有重复序列的质粒或萤光素酶测定质粒(包含编码萤光素酶蛋白的mRNA序列)共转染。在将RNA内切核酸酶/Cas9融合物与重复性RNA共转染的条件下用qPCR测量含有CTG重复的RNA的水平。在将RNA内切核酸酶/Cas9融合物与萤光素酶测定质粒共转染的条件下使用发光测定测量萤光素酶蛋白的水平。将所有测量值针对非靶向sgRNA对照构建体进行归一化(图3A-图5和图9)。
实施例3：病毒RNA分子的RNA指导的切割
将A549细胞在含有10％FBS和1％青霉素/链霉素的DMEM(GIBCO)中培养，并以90％-100％汇合度进行传代。将细胞以1x 10^5个细胞/孔接种于24孔板中用于RNA分离，或以.5x 10^5个细胞/孔接种。将细胞用与基因NTHL1(残基31-312，E43)或CPSF4L(全长，E67)融合的编码空肠弯曲杆菌Cas9(CjeCas9)的质粒与编码Zika NS5 RNA中的四个位点之一的质粒转染。CjeCas9是由EFS启动子驱动的，而指导RNA是由U6启动子驱动的。sgRNA的序列呈现于表1中。此项研究中使用的构建体的序列呈现于下文中。
RNA分离是用RNAeasy柱(Qiagen)根据制造商的方案来进行。使用Nanodrop分光光度计来估计RNA质量和浓度。使用Superscript III(Thermo)以随机引物根据制造商的方案进行cDNA制备。用如表2中所列的以下引物进行qPCR。
图7显示了在E43和E67内切核酸酶二者的存在下用含有如表2中指示的各种靶向NS5的间隔子序列的sgRNA评估的Zika NS5的表达水平。将Zika NS5表达展示为相对于加载有含有对照(λ)间隔子序列的sgRNA的内切核酸酶的变化倍数。
使用免疫荧光显微镜检查将在与CjeCas9融合的E43或E67内切核酸酶的存在下的Zika NS5表达可视化。图8A显示了用加载有含有靶向ZikaNS5的间隔子序列的sgRNA的CjeCas9-内切核酸酶融合物转染的细胞的荧光显微镜检查图像。如与加载有不靶向ZikaNS5的sgRNA的CjeCas9-内切核酸酶融合物相比，在加载有靶向Zika NS5的适当sgRNA的CjeCas9-内切核酸酶融合物的存在下，Zika NS5的表达显著降低(图8A和图8B)。图6是用于本公开文本的组合物中的示例性内切核酸酶的列表。
表1：qPCR引物
GAPDH_F CAGCCTCAAGATCATCAGCAA(SEQ ID NO:192)
GAPDH_R TGTGGTCATGAGTCCTTCCA(SEQ ID NO:193)
NS5_F GAGGAGAGTGCCAGAGTTGT(SEQ ID NO:194)
NS5_R TCTCTCTCCCCATCCAGTGA(SEQ ID NO:195)
表2：sgRNA序列
Figure BDA0002919433300001331
Figure BDA0002919433300001341
E43-CjeCas9和sgRNA质粒可以包含以下序列或由其组成(U6：N＝sgRNA间隔子，E43，CjeCas9)：
gtttattacagggacagcagagatccagtttggttaattaaggtaccgagggcctatttcccatgatt ccttcatatttgcatatacgatacaaggctgttagagagataattagaattaatttgactgtaaacacaaagatat tagtacaaaatacgtgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaaaatgga ctatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttGTGGAAAGGACGAAACACCNNNNNNNNNNNNNNNNNNNGTTTTAGTCCCTGAAGGGACTAAAATAAAGAGTTTGCGGGACTCTGCGGGGTTACAATCCCCTAAAACCGCTTTTTTTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTGCGCGAATTCGCTAGCTAGGTCTTGAAAGGAGTGGGAATTGGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGATCCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACAGGACCGGTTCTAGAGCGCTATTTAGAACCatgTGTTCTCCCCAAGAATCTGGCATGACCGCTCTTTCAGCGAGGATGTTGACGCGAAGCAGATCCCTGGGACCTGGGGCCGGGCCACGAGGGTGTCGGGAAGAACCAGGACCGTTGCGACGGAGGGAAGCAGCAGCGGAAGCTCGGAAATCCCATTCTCCGGTTAAACGACCCCGCAAGGCACAACGGCTCAGGGTTGCTTACGAGGGGAGCGATTCCGAAAAGGGTGAAGGAGCAGAGCCCTTGAAGGTTCCAGTATGGGAACCCCAGGATTGGCAGCAGCAGCTTGTAAACATCCGAGCAATGAGGAACAAAAAAGATGCACCTGTTGATCACCTCGGAACCGAACATTGTTATGATTCTAGTGCGCCGCCAAAAGTCCGCCGGTATCAGGTTCTGTTGAGTTTGATGCTGAGTAGTCAGACTAAGGACCAGGTTACGGCCGGAGCAATGCAACGGCTTCGGGCACGGGGACTCACGGTCGATAGCATTTTGCAGACCGATGACGCAACATTGGGTAAACTCATATATCCAGTTGGCTTCTGGCGGAGCAAAGTGAAGTACATCAAGCAGACCTCAGCCATTCTCCAACAACATTACGGAGGTGATATACCCGCAAGCGTAGCTGAACTGGTAGCACTGCCGGGCGTCGGTCCCAAAATGGCACATCTGGCTATGGCGGTTGCTTGGGGAACGGTGTCTGGTATCGCAGTTGATACGCATGTCCACCGCATCGCCAATCGGCTGAGGTGGACTAAAAAAGCCACTAAGTCTCCTGAAGAAACACGGGCTGCTCTGGAAGAGTGGCTTCCACGAGAGCTGTGGCATGAAATCAATGGATTGCTGGTTGGTTTCGGGCAGCAGACATGCTTGCCCGTGCACCCCCGGTGTCATGCTTGCTTGAACCAGGCTTTGTGCCCAGCTGCCCAGGGCCTGAGTGGAAGTGAGACACCGGGAACATCTGAGTCTGCGACCCCGGAGAGCacaaacGCGCGAATCCTGGCCTTCGcgATTGGCATTAGCAGCATCGGCTGGGCA TTCTCTGAAAACGACGAACTGAAGGATTGCGGCGTGCGAATTTTCACTAAGGTCGAAAATCCCAAAACTGGTGAAT CACTCGCTCTCCCTAGACGACTGGCACGCTCCGCACGAAAGAGGCTTGCCCGCCGCAAGGCACGCTTGAACCATCT TAAACACCTTATTGCAAATGAGTTTAAACTGAATTATGAGGACTACCAATCCTTTGACGAGTCTCTTGCTAAAGCC TACAAAGGGAGCCTTATATCCCCGTATGAGCTCCGGTTCAGAGCACTCAACGAACTGCTGTCCAAACAGGATTTTG CTCGCGTGATTCTCCACATAGCGAAGAGGCGAGGATACGATGACATTAAAAACAGTGATGATAAGGAAAAAGGGGC CATACTCAAAGCGATTAAGCAAAATGAAGAGAAGCTCGCTAACTATCAATCAGTAGGGGAGTATCTCTATAAAGAG TACTTCCAGAAGTTCAAAGAAAATAGCAAGGAATTTACTAATGTCCGGAATAAAAAGGAGTCTTACGAAAGATGTA TTGCGCAATCTTTCCTCAAGGACGAGCTCAAATTGATTTTCAAGAAACAAAGGGAATTTGGGTTCAGCTTCTCAAA AAAATTTGAGGAAGAGGTTCTGAGCGTTGCCTTTTACAAACGCGCCCTTAAGGACTTCTCACATCTCGTAGGGAAT TGTAGTTTCTTCACCGATGAAAAACGGGCGCCAAAAAATAGCCCTTTGGCTTTTATGTTTGTCGCTCTGACTCGCA TCATTAATCTGCTCAACAACCTTAAAAACACGGAAGGGATTCTGTACACAAAGGATGATCTGAACGCTCTGCTTAA CGAAGTTTTGAAGAACGGGACTTTGACCTACAAACAAACCAAAAAGCTTCTTGGTCTCAGTGATGACTACGAATTC AAGGGAGAAAAAGGGACATATTTCATCGAATTCAAGAAGTATAAGGAGTTCATCAAAGCCTTGGGCGAGCACAACT TGTCTCAAGATGATCTCAACGAAATTGCTAAGGATATCACTCTGATTAAAGACGAGATCAAGCTCAAAAAGGCGTT GGCGAAGTATGACCTTAACCAAAACCAAATAGATAGCCTCAGCAAGTTGGAATTTAAAGATCACTTGAATATAAGT TTCAAGGCCCTTAAGTTGGTCACCCCCTTGATGCTTGAAGGAAAGAAATATGATGAGGCATGTAATGAGCTGAATC TCAAGGTTGCTATTAACGAAGACAAAAAAGATTTCCTCCCAGCTTTCAATGAGACTTACTATAAGGACGAGGTTAC CAATCCTGTGGTGCTCCGAGCCATCAAAGAGTATCGAAAGGTCCTGAATGCTTTGCTCAAAAAATACGGTAAGGTA CACAAAATAAATATTGAGCTCGCAAGGGAGGTCGGTAAGAACCACTCCCAGCGCGCCAAAATAGAAAAGGAACAGA ATGAAAATTACAAAGCGAAAAAGGACGCCGAGCTCGAGTGCGAAAAGCTGGGCCTGAAAATAAACAGCAAGAACAT TCTCAAACTCCGCCTCTTCAAAGAACAAAAAGAATTTTGTGCTTATAGTGGTGAGAAAATAAAAATCTCCGATCTT CAAGACGAGAAGATGCTCGAAATAGACgcgATATATCCATATAGCAGGTCTTTTGACGATTCTTACATGAATAAAG TGCTTGTTTTCACTAAGCAGAATCAGGAAAAGTTGAATCAGACCCCCTTTGAGGCCTTTGGCAACGACTCAGCAAA GTGGCAGAAGATCGAGGTCTTGGCTAAGAATCTTCCTACTAAGAAACAGAAAAGGATATTGGATAAGAACTATAAA GACAAAGAACAAAAGAACTTTAAAGACCGCAACCTCAATGACACCAGATACATAGCAAGATTGGTTCTGAACTACA CAAAAGATTATTTGGACTTCTTGCCGCTGTCTGATGATGAGAACACGAAACTCAACGACACGCAAAAGGGGTCTAA AGTCCACGTCGAAGCTAAATCTGGGATGCTCACCTCAGCATTGAGGCATACGTGGGGATTCTCAGCAAAGGACCGA AACAATCACCTGCACCATGCCATTGACGCAGTTATCATAGCGTATGCCAATAATTCAATAGTAAAAGCGTTTAGCG ACTTCAAGAAGGAACAAGAGTCCAACAGCGCCGAGCTCTACGCAAAAAAGATTAGTGAACTCGACTACAAAAACAA AAGAAAATTCTTTGAGCCGTTCAGCGGATTTCGACAGAAGGTATTGGATAAAATAGATGAAATTTTCGTGAGCAAA CCCGAAAGGAAAAAGCCCTCAGGCGCCTTGCACGAAGAGACTTTCAGGAAGGAAGAGGAATTCTACCAAAGCTACG GCGGAAAAGAGGGAGTTTTGAAGGCTCTCGAACTTGGAAAGATTAGGAAGGTGAACGGCAAGATAGTGAAAAACGG CGATATGTTCCGGGTTGATATCTTCAAACATAAAAAAACGAATAAATTTTATGCTGTGCCTATATACACTATGGAC TTCGCACTTAAGGTCCTGCCGAATAAGGCGGTAGCCCGATCTAAAAAAGGCGAAATTAAGGACTGGATTTTGATGG ATGAAAATTACGAGTTCTGCTTTTCTCTCTACAAGGATTCCCTTATATTGATACAGACGAAAGATATGCAGGAACC GGAATTCGTGTATTACAACGCTTTTACTTCCTCTACGGTATCTTTGATTGTCTCCAAACATGACAACAAATTCGAA ACACTCAGTAAAAACCAAAAGATTCTCTTTAAAAATGCGAACGAGAAAGAAGTAATTGCAAAATCAATTGGCATCC AAAATTTGAAAGTTTTTGAAAAATATATAGTATCTGCCCTCGGAGAGGTTACTAAAGCGGAATTTAGACAGCGAGA GGACTTCAAAAAATCAGGTCCACCCAAGAAAAAACGCAAGGTGGAAGATCCGAAGAAAAAGCGAAAAGTGGATGTGtaaCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTATACCG(SEQ ID NO:202)。
E67-CjeCas9和sgRNA质粒可以包含以下序列或由其组成(U6：N＝sgRNA间隔子，E67，CjeCas9)：
gtttattacagggacagcagagatccagtttggttaattaaggtaccgagggcctatttcccatgatt ccttcatatttgcatatacgatacaaggctgttagagagataattagaattaatttgactgtaaacacaaagatat tagtacaaaatacgtgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaaaatgga ctatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttGTGGAAAGGACGAAACACCNNNNNNNNNNNNNNNNNNNGTTTTAGTCCCTGAAGGGACTAAAATAAAGAGTTTGCGGGACTCTGCGGGGTTACAATCCCCTAAAACCGCTTTTTTTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTGCGCGAATTCGCTAGCTAGGTCTTGAAAGGAGTGGGAATTGGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGATCCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACAGGACCGGTTCTAGAGCGCTATTTAGAACCatgCAGGAGGTAATAGCGGGGCTTGAGCGATTTACCTTTGCCTTCGAAAAAGACGTAGAGATGCAGAAGGGAACCGGCCTGCTCCCATTTCAAGGTATGGACAAATCAGCATCTGCCGTGTGCAATTTTTTCACCAAGGGTCTGTGTGAAAAGGGGAAGCTCTGTCCATTTCGCCATGATCGCGGAGAGAAGATGGTGGTGTGTAAGCACTGGCTGAGAGGGCTTTGCAAAAAAGGCGACCACTGCAAATTTCTTCACCAATATGACCTGACTCGAATGCCTGAGTGTTATTTTTACAGTAAGTTCGGTGACTGTAGCAACAAAGAATGCAGCTTCTTGCATGTCAAACCAGCATTCAAGTCACAGGATTGCCCGTGGTACGATCAGGGTTTTTGCAAGGACGGTCCCCTCTGCAAATATCGACACGTACCCAGAATTATGTGCCTTAATTACCTGGTCGGCTTCTGTCCTGAAGGGCCAAAATGTCAGTTTGCTCAAAAAATTCGCGAGTTCAAATTGCTCCCTGGGTCTAAAATTTGGGAACCCCAGGATTGGCAGCAGCAGCTTGTAAACATCCGAGCAATGAGGAACAAAAAAGATGCACCTGTTGATCACCTCGGAACCGAACATTGTTATGATTCTAGTGCGCCGCCAAAAGTCCGCCGGTATCAGGTTCTGTTGAGTTTGATGCTGAGTAGTCAGACTAAGGACCAGGTTACGGCCGGAGCAATGCAACGGCTTCGGGCACGGGGACTCACGGTCGATAGCATTTTGCAGACCGATGACGCAACATTGGGTAAACTCATATATCCAGTTGGCTTCTGGCGGAGCAAAGTGAAGTACATCAAGCAGACCTCAGCCATTCTCCAACAACATTACGGAGGTGATATACCCGCAAGCGTAGCTGAACTGGTAGCACTGCCGGGCGTCGGTCCCAAAATGGCACATCTGGCTATGGCGGTTGCTTGGGGAACGGTGTCTGGTATCGCAGTTGATACGCATGTCCACCGCATCGCCAATCGGCTGAGGTGGACTAAAAAAGCCACTAAGTCTCCTGAAGAAACACGGGCTGCTCTGGAAGAGTGGCTTCCACGAGAGCTGTGGCATGAAATCAATGGATTGCTGGTTGGTTTCGGGCAGCAGACATGCTTGCCCGTGCACCCCCGGTGTCATGCTTGCTTGAACCAGGCTTTGTGCCCAGCTGCCCAGGGCCTGAGTGGAAGTGAGACACCGGGAACATCTGAGTCTGCGACCCCGGAGAGCacaaacGCGCGAATCCTGGCCTTCGcgATTGGCATTAGCAGCATCGGCTGGGCATTCTCTGAAAACGACGAACTGAAGG ATTGCGGCGTGCGAATTTTCACTAAGGTCGAAAATCCCAAAACTGGTGAATCACTCGCTCTCCCTAGACGACTGGC ACGCTCCGCACGAAAGAGGCTTGCCCGCCGCAAGGCACGCTTGAACCATCTTAAACACCTTATTGCAAATGAGTTT AAACTGAATTATGAGGACTACCAATCCTTTGACGAGTCTCTTGCTAAAGCCTACAAAGGGAGCCTTATATCCCCGT ATGAGCTCCGGTTCAGAGCACTCAACGAACTGCTGTCCAAACAGGATTTTGCTCGCGTGATTCTCCACATAGCGAA GAGGCGAGGATACGATGACATTAAAAACAGTGATGATAAGGAAAAAGGGGCCATACTCAAAGCGATTAAGCAAAAT GAAGAGAAGCTCGCTAACTATCAATCAGTAGGGGAGTATCTCTATAAAGAGTACTTCCAGAAGTTCAAAGAAAATA GCAAGGAATTTACTAATGTCCGGAATAAAAAGGAGTCTTACGAAAGATGTATTGCGCAATCTTTCCTCAAGGACGA GCTCAAATTGATTTTCAAGAAACAAAGGGAATTTGGGTTCAGCTTCTCAAAAAAATTTGAGGAAGAGGTTCTGAGC GTTGCCTTTTACAAACGCGCCCTTAAGGACTTCTCACATCTCGTAGGGAATTGTAGTTTCTTCACCGATGAAAAAC GGGCGCCAAAAAATAGCCCTTTGGCTTTTATGTTTGTCGCTCTGACTCGCATCATTAATCTGCTCAACAACCTTAA AAACACGGAAGGGATTCTGTACACAAAGGATGATCTGAACGCTCTGCTTAACGAAGTTTTGAAGAACGGGACTTTG ACCTACAAACAAACCAAAAAGCTTCTTGGTCTCAGTGATGACTACGAATTCAAGGGAGAAAAAGGGACATATTTCA TCGAATTCAAGAAGTATAAGGAGTTCATCAAAGCCTTGGGCGAGCACAACTTGTCTCAAGATGATCTCAACGAAAT TGCTAAGGATATCACTCTGATTAAAGACGAGATCAAGCTCAAAAAGGCGTTGGCGAAGTATGACCTTAACCAAAAC CAAATAGATAGCCTCAGCAAGTTGGAATTTAAAGATCACTTGAATATAAGTTTCAAGGCCCTTAAGTTGGTCACCC CCTTGATGCTTGAAGGAAAGAAATATGATGAGGCATGTAATGAGCTGAATCTCAAGGTTGCTATTAACGAAGACAA AAAAGATTTCCTCCCAGCTTTCAATGAGACTTACTATAAGGACGAGGTTACCAATCCTGTGGTGCTCCGAGCCATC AAAGAGTATCGAAAGGTCCTGAATGCTTTGCTCAAAAAATACGGTAAGGTACACAAAATAAATATTGAGCTCGCAA GGGAGGTCGGTAAGAACCACTCCCAGCGCGCCAAAATAGAAAAGGAACAGAATGAAAATTACAAAGCGAAAAAGGA CGCCGAGCTCGAGTGCGAAAAGCTGGGCCTGAAAATAAACAGCAAGAACATTCTCAAACTCCGCCTCTTCAAAGAA CAAAAAGAATTTTGTGCTTATAGTGGTGAGAAAATAAAAATCTCCGATCTTCAAGACGAGAAGATGCTCGAAATAG ACgcgATATATCCATATAGCAGGTCTTTTGACGATTCTTACATGAATAAAGTGCTTGTTTTCACTAAGCAGAATCA GGAAAAGTTGAATCAGACCCCCTTTGAGGCCTTTGGCAACGACTCAGCAAAGTGGCAGAAGATCGAGGTCTTGGCT AAGAATCTTCCTACTAAGAAACAGAAAAGGATATTGGATAAGAACTATAAAGACAAAGAACAAAAGAACTTTAAAG ACCGCAACCTCAATGACACCAGATACATAGCAAGATTGGTTCTGAACTACACAAAAGATTATTTGGACTTCTTGCC GCTGTCTGATGATGAGAACACGAAACTCAACGACACGCAAAAGGGGTCTAAAGTCCACGTCGAAGCTAAATCTGGG ATGCTCACCTCAGCATTGAGGCATACGTGGGGATTCTCAGCAAAGGACCGAAACAATCACCTGCACCATGCCATTG ACGCAGTTATCATAGCGTATGCCAATAATTCAATAGTAAAAGCGTTTAGCGACTTCAAGAAGGAACAAGAGTCCAA CAGCGCCGAGCTCTACGCAAAAAAGATTAGTGAACTCGACTACAAAAACAAAAGAAAATTCTTTGAGCCGTTCAGC GGATTTCGACAGAAGGTATTGGATAAAATAGATGAAATTTTCGTGAGCAAACCCGAAAGGAAAAAGCCCTCAGGCG CCTTGCACGAAGAGACTTTCAGGAAGGAAGAGGAATTCTACCAAAGCTACGGCGGAAAAGAGGGAGTTTTGAAGGC TCTCGAACTTGGAAAGATTAGGAAGGTGAACGGCAAGATAGTGAAAAACGGCGATATGTTCCGGGTTGATATCTTC AAACATAAAAAAACGAATAAATTTTATGCTGTGCCTATATACACTATGGACTTCGCACTTAAGGTCCTGCCGAATA AGGCGGTAGCCCGATCTAAAAAAGGCGAAATTAAGGACTGGATTTTGATGGATGAAAATTACGAGTTCTGCTTTTC TCTCTACAAGGATTCCCTTATATTGATACAGACGAAAGATATGCAGGAACCGGAATTCGTGTATTACAACGCTTTT ACTTCCTCTACGGTATCTTTGATTGTCTCCAAACATGACAACAAATTCGAAACACTCAGTAAAAACCAAAAGATTC TCTTTAAAAATGCGAACGAGAAAGAAGTAATTGCAAAATCAATTGGCATCCAAAATTTGAAAGTTTTTGAAAAATA TATAGTATCTGCCCTCGGAGAGGTTACTAAAGCGGAATTTAGACAGCGAGAGGACTTCAAAAAATCAGGTCCACCCAAGAAAAAACGCAAGGTGGAAGATCCGAAGAAAAAGCGAAAAGTGGATGTGtaaCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTATACCG(SEQ ID NO:203)。
通过引用并入
将在本文中引用的每个文件(包括任何交叉参考或相关的专利或申请)通过引用以其整体特此并入本文，除非明确排除或另有限制。引用任何文件并非承认，它是关于本文公开或具体化的任何发明的现有技术，或者它单独地或与任何其他一个或多个参考文献的任何组合传授、表明或公开任何这种发明。此外，在本文件中术语的任何含义或定义与通过引用并入的文件中相同术语的任何含义或定义矛盾的方面来说，应当以分配给本文件中该术语的含义或定义为准。
其他实施方案
虽然已经说明并描述了本公开文本的特定实施方案，但是可以在不背离本公开文本的精神和范围的情况下做出各种其他变化和修改。所附权利要求的范围包括在本公开文本的范围内的所有此类变化和修改。
序列表
<110> 洛卡纳生物股份有限公司
<120> 靶向RNA的融合蛋白组合物和使用方法
<130> LOCN-002/001WO 330675-2007
<150> US 62/682,271
<151> 2018-06-08
<160> 208
<170> PatentIn3.5版
<210> 1
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 1
uggagcgagc aucccccaaa 20
<210> 2
<211> 21
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 2
guuuggggga ugcucgcucc a 21
<210> 3
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 3
cccucacugc uggggagucc 20
<210> 4
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 4
ggacucccca gcagugaggg 20
<210> 5
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 5
gcaacuggau caauuugcug 20
<210> 6
<211> 21
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 6
gcagcaaauu gauccaguug c 21
<210> 7
<211> 21
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 7
gcauucuuau cuggucagug c 21
<210> 8
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 8
gcacugacca gauaagaaug 20
<210> 9
<211> 21
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 9
gagcagcagc agcagcagca g 21
<210> 10
<211> 21
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 10
gcaggcaggc aggcaggcag g 21
<210> 11
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 11
gccccggccc cggccccggc 20
<210> 12
<211> 20
<212> DNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 12
gctgctgctg ctgctgctgc 20
<210> 13
<211> 93
<212> RNA
<213> 人工序列
<220>
<223> 支架序列
<400> 13
guuuaagagc uaugcuggaa acagcauagc aaguuuaaau aaggcuaguc cguuaucaac 60
uugaaaaagu ggcaccgagu cggugcuuuu uuu 93
<210> 14
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 14
gugauaagug gaaugccaug 20
<210> 15
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 15
cuggugaacu uccgauagug 20
<210> 16
<211> 20
<212> DNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 16
gagatatagc ctggtggttc 20
<210> 17
<211> 73
<212> RNA
<213> 人工序列
<220>
<223> 支架序列
<400> 17
ggacagcaua gcaaguuaaa auaaggcuag uccguuauca acuugaaaaa guggcaccga 60
gucggugcuu uuu 73
<210> 18
<211> 3
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 18
cug 3
<210> 19
<211> 4
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 19
ccug 4
<210> 20
<211> 128
<212> PRT
<213> 未知的
<220>
<223> RNA酶1
<400> 20
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Leu Cys Lys Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asn Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Asn Gly Ser Arg Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val His Phe Asp Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 21
<211> 119
<212> PRT
<213> 未知的
<220>
<223> RNA酶4
<400> 21
Gln Asp Gly Met Tyr Gln Arg Phe Leu Arg Gln His Val His Pro Glu
1 5 10 15
Glu Thr Gly Gly Ser Asp Arg Tyr Cys Asp Leu Met Met Gln Arg Arg
20 25 30
Lys Met Thr Leu Tyr His Cys Lys Arg Phe Asn Thr Phe Ile His Glu
35 40 45
Asp Ile Trp Asn Ile Arg Ser Ile Cys Ser Thr Thr Asn Ile Gln Cys
50 55 60
Lys Asn Gly Lys Met Asn Cys His Glu Gly Val Val Lys Val Thr Asp
65 70 75 80
Cys Arg Asp Thr Gly Ser Ser Arg Ala Pro Asn Cys Arg Tyr Arg Ala
85 90 95
Ile Ala Ser Thr Arg Arg Val Val Ile Ala Cys Glu Gly Asn Pro Gln
100 105 110
Val Pro Val His Phe Asp Gly
115
<210> 22
<211> 127
<212> PRT
<213> 未知的
<220>
<223> RNA酶6
<400> 22
Trp Pro Lys Arg Leu Thr Lys Ala His Trp Phe Glu Ile Gln His Ile
1 5 10 15
Gln Pro Ser Pro Leu Gln Cys Asn Arg Ala Met Ser Gly Ile Asn Asn
20 25 30
Tyr Thr Gln His Cys Lys His Gln Asn Thr Phe Leu His Asp Ser Phe
35 40 45
Gln Asn Val Ala Ala Val Cys Asp Leu Leu Ser Ile Val Cys Lys Asn
50 55 60
Arg Arg His Asn Cys His Gln Ser Ser Lys Pro Val Asn Met Thr Asp
65 70 75 80
Cys Arg Leu Thr Ser Gly Lys Tyr Pro Gln Cys Arg Tyr Ser Ala Ala
85 90 95
Ala Gln Tyr Lys Phe Phe Ile Val Ala Cys Asp Pro Pro Gln Lys Ser
100 105 110
Asp Pro Pro Tyr Lys Leu Val Pro Val His Leu Asp Ser Ile Leu
115 120 125
<210> 23
<211> 155
<212> PRT
<213> 未知的
<220>
<223> RNA酶7
<400> 23
Ala Pro Ala Arg Ala Gly Phe Cys Pro Leu Leu Leu Leu Leu Leu Leu
1 5 10 15
Gly Leu Trp Val Ala Glu Ile Pro Val Ser Ala Lys Pro Lys Gly Met
20 25 30
Thr Ser Ser Gln Trp Phe Lys Ile Gln His Met Gln Pro Ser Pro Gln
35 40 45
Ala Cys Asn Ser Ala Met Lys Asn Ile Asn Lys His Thr Lys Arg Cys
50 55 60
Lys Asp Leu Asn Thr Phe Leu His Glu Pro Phe Ser Ser Val Ala Ala
65 70 75 80
Thr Cys Gln Thr Pro Lys Ile Ala Cys Lys Asn Gly Asp Lys Asn Cys
85 90 95
His Gln Ser His Gly Pro Val Ser Leu Thr Met Cys Lys Leu Thr Ser
100 105 110
Gly Lys Tyr Pro Asn Cys Arg Tyr Lys Glu Lys Arg Gln Asn Lys Ser
115 120 125
Tyr Val Val Ala Cys Lys Pro Pro Gln Lys Lys Asp Ser Gln Gln Phe
130 135 140
His Leu Val Pro Val His Leu Asp Arg Val Leu
145 150 155
<210> 24
<211> 122
<212> PRT
<213> 未知的
<220>
<223> RNA酶8
<400> 24
Thr Ser Ser Gln Trp Phe Lys Thr Gln His Val Gln Pro Ser Pro Gln
1 5 10 15
Ala Cys Asn Ser Ala Met Ser Ile Ile Asn Lys Tyr Thr Glu Arg Cys
20 25 30
Lys Asp Leu Asn Thr Phe Leu His Glu Pro Phe Ser Ser Val Ala Ile
35 40 45
Thr Cys Gln Thr Pro Asn Ile Ala Cys Lys Asn Ser Cys Lys Asn Cys
50 55 60
His Gln Ser His Gly Pro Met Ser Leu Thr Met Gly Glu Leu Thr Ser
65 70 75 80
Gly Lys Tyr Pro Asn Cys Arg Tyr Lys Glu Lys His Leu Asn Thr Pro
85 90 95
Tyr Ile Val Ala Cys Asp Pro Pro Gln Gln Gly Asp Pro Gly Tyr Pro
100 105 110
Leu Val Pro Val His Leu Asp Lys Val Val
115 120
<210> 25
<211> 134
<212> PRT
<213> 未知的
<220>
<223> RNA酶2
<400> 25
Lys Pro Pro Gln Phe Thr Trp Ala Gln Trp Phe Glu Thr Gln His Ile
1 5 10 15
Asn Met Thr Ser Gln Gln Cys Thr Asn Ala Met Gln Val Ile Asn Asn
20 25 30
Tyr Gln Arg Arg Cys Lys Asn Gln Asn Thr Phe Leu Leu Thr Thr Phe
35 40 45
Ala Asn Val Val Asn Val Cys Gly Asn Pro Asn Met Thr Cys Pro Ser
50 55 60
Asn Lys Thr Arg Lys Asn Cys His His Ser Gly Ser Gln Val Pro Leu
65 70 75 80
Ile His Cys Asn Leu Thr Thr Pro Ser Pro Gln Asn Ile Ser Asn Cys
85 90 95
Arg Tyr Ala Gln Thr Pro Ala Asn Met Phe Tyr Ile Val Ala Cys Asp
100 105 110
Asn Arg Asp Gln Arg Arg Asp Pro Pro Gln Tyr Pro Val Val Pro Val
115 120 125
His Leu Asp Arg Ile Ile
130
<210> 26
<211> 216
<212> PRT
<213> 未知的
<220>
<223> RNA酶6PL
<400> 26
Asp Lys Arg Leu Arg Asp Asn His Glu Trp Lys Lys Leu Ile Met Val
1 5 10 15
Gln His Trp Pro Glu Thr Val Cys Glu Lys Ile Gln Asn Asp Cys Arg
20 25 30
Asp Pro Pro Asp Tyr Trp Thr Ile His Gly Leu Trp Pro Asp Lys Ser
35 40 45
Glu Gly Cys Asn Arg Ser Trp Pro Phe Asn Leu Glu Glu Ile Lys Lys
50 55 60
Asn Trp Met Glu Ile Thr Asp Ser Ser Leu Pro Ser Pro Ser Met Gly
65 70 75 80
Pro Ala Pro Pro Arg Trp Met Arg Ser Thr Pro Arg Arg Ser Thr Leu
85 90 95
Ala Glu Ala Trp Asn Ser Thr Gly Ser Trp Thr Ser Thr Gly Gly Cys
100 105 110
Ala Leu Pro Pro Ala Ala Leu Pro Ser Gly Asp Leu Cys Cys Arg Pro
115 120 125
Ser Leu Thr Ala Gly Ser Arg Gly Val Gly Val Asp Leu Thr Ala Leu
130 135 140
His Gln Leu Leu His Val His Tyr Ser Ala Thr Gly Ile Ile Pro Glu
145 150 155 160
Glu Cys Ser Glu Pro Thr Lys Pro Phe Gln Ile Ile Leu His His Asp
165 170 175
His Thr Glu Trp Val Gln Ser Ile Gly Met Pro Ile Trp Gly Thr Ile
180 185 190
Ser Ser Ser Glu Ser Ala Ile Gly Lys Asn Glu Glu Ser Gln Pro Ala
195 200 205
Cys Ala Val Leu Ser His Asp Ser
210 215
<210> 27
<211> 722
<212> PRT
<213> 未知的
<220>
<223> RNA酶L
<400> 27
Ala Ala Val Glu Asp Asn His Leu Leu Ile Lys Ala Val Gln Asn Glu
1 5 10 15
Asp Val Asp Leu Val Gln Gln Leu Leu Glu Gly Gly Ala Asn Val Asn
20 25 30
Phe Gln Glu Glu Glu Gly Gly Trp Thr Pro Leu His Asn Ala Val Gln
35 40 45
Met Ser Arg Glu Asp Ile Val Glu Leu Leu Leu Arg His Gly Ala Asp
50 55 60
Pro Val Leu Arg Lys Lys Asn Gly Ala Thr Pro Phe Ile Leu Ala Ala
65 70 75 80
Ile Ala Gly Ser Val Lys Asp Leu Leu Lys Leu Phe Leu Ser Lys Gly
85 90 95
Ala Asp Val Asn Glu Cys Asp Phe Tyr Gly Phe Thr Ala Phe Met Glu
100 105 110
Ala Ala Val Tyr Gly Lys Val Lys Ala Leu Lys Phe Leu Tyr Lys Arg
115 120 125
Gly Ala Asn Val Asn Leu Arg Arg Lys Thr Lys Glu Asp Gln Glu Arg
130 135 140
Leu Arg Lys Gly Gly Ala Thr Ala Leu Met Asp Ala Ala Glu Lys Gly
145 150 155 160
His Val Glu Val Leu Lys Ile Leu Leu Asp Glu Met Gly Ala Asp Val
165 170 175
Asn Ala Cys Asp Asn Met Gly Arg Asn Ala Leu Ile His Ala Leu Leu
180 185 190
Ser Ser Asp Asp Ser Asp Val Glu Ala Ile Thr His Leu Leu Leu Asp
195 200 205
His Gly Ala Asp Val Asn Val Arg Gly Glu Arg Gly Lys Thr Pro Leu
210 215 220
Ile Leu Ala Val Glu Lys Lys His Leu Gly Leu Val Gln Arg Leu Leu
225 230 235 240
Glu Gln Glu His Ile Glu Ile Asn Asp Thr Asp Ser Asp Gly Lys Thr
245 250 255
Ala Leu Leu Leu Ala Val Glu Leu Lys Leu Lys Lys Ile Ala Glu Leu
260 265 270
Leu Cys Lys Arg Gly Ala Ser Thr Asp Cys Gly Asp Leu Val Met Thr
275 280 285
Ala Arg Arg Asn Tyr Asp His Ser Leu Val Lys Val Leu Leu Ser His
290 295 300
Gly Ala Lys Glu Asp Phe His Pro Pro Ala Glu Asp Trp Lys Pro Gln
305 310 315 320
Ser Ser His Trp Gly Ala Ala Leu Lys Asp Leu His Arg Ile Tyr Arg
325 330 335
Pro Met Ile Gly Lys Leu Lys Phe Phe Ile Asp Glu Lys Tyr Lys Ile
340 345 350
Ala Asp Thr Ser Glu Gly Gly Ile Tyr Leu Gly Phe Tyr Glu Lys Gln
355 360 365
Glu Val Ala Val Lys Thr Phe Cys Glu Gly Ser Pro Arg Ala Gln Arg
370 375 380
Glu Val Ser Cys Leu Gln Ser Ser Arg Glu Asn Ser His Leu Val Thr
385 390 395 400
Phe Tyr Gly Ser Glu Ser His Arg Gly His Leu Phe Val Cys Val Thr
405 410 415
Leu Cys Glu Gln Thr Leu Glu Ala Cys Leu Asp Val His Arg Gly Glu
420 425 430
Asp Val Glu Asn Glu Glu Asp Glu Phe Ala Arg Asn Val Leu Ser Ser
435 440 445
Ile Phe Lys Ala Val Gln Glu Leu His Leu Ser Cys Gly Tyr Thr His
450 455 460
Gln Asp Leu Gln Pro Gln Asn Ile Leu Ile Asp Ser Lys Lys Ala Ala
465 470 475 480
His Leu Ala Asp Phe Asp Lys Ser Ile Lys Trp Ala Gly Asp Pro Gln
485 490 495
Glu Val Lys Arg Asp Leu Glu Asp Leu Gly Arg Leu Val Leu Tyr Val
500 505 510
Val Lys Lys Gly Ser Ile Ser Phe Glu Asp Leu Lys Ala Gln Ser Asn
515 520 525
Glu Glu Val Val Gln Leu Ser Pro Asp Glu Glu Thr Lys Asp Leu Ile
530 535 540
His Arg Leu Phe His Pro Gly Glu His Val Arg Asp Cys Leu Ser Asp
545 550 555 560
Leu Leu Gly His Pro Phe Phe Trp Thr Trp Glu Ser Arg Tyr Arg Thr
565 570 575
Leu Arg Asn Val Gly Asn Glu Ser Asp Ile Lys Thr Arg Lys Ser Glu
580 585 590
Ser Glu Ile Leu Arg Leu Leu Gln Pro Gly Pro Ser Glu His Ser Lys
595 600 605
Ser Phe Asp Lys Trp Thr Thr Lys Ile Asn Glu Cys Val Met Lys Lys
610 615 620
Met Asn Lys Phe Tyr Glu Lys Arg Gly Asn Phe Tyr Gln Asn Thr Val
625 630 635 640
Gly Asp Leu Leu Lys Phe Ile Arg Asn Leu Gly Glu His Ile Asp Glu
645 650 655
Glu Lys His Lys Lys Met Lys Leu Lys Ile Gly Asp Pro Ser Leu Tyr
660 665 670
Phe Gln Lys Thr Phe Pro Asp Leu Val Ile Tyr Val Tyr Thr Lys Leu
675 680 685
Gln Asn Thr Glu Tyr Arg Lys His Phe Pro Gln Thr His Ser Pro Asn
690 695 700
Lys Pro Gln Cys Asp Gly Ala Gly Gly Ala Ser Gly Leu Ala Ser Pro
705 710 715 720
Gly Cys
<210> 28
<211> 217
<212> PRT
<213> 未知的
<220>
<223> RNA酶T2
<400> 28
Val Gln His Trp Pro Glu Thr Val Cys Glu Lys Ile Gln Asn Asp Cys
1 5 10 15
Arg Asp Pro Pro Asp Tyr Trp Thr Ile His Gly Leu Trp Pro Asp Lys
20 25 30
Ser Glu Gly Cys Asn Arg Ser Trp Pro Phe Asn Leu Glu Glu Ile Lys
35 40 45
Asp Leu Leu Pro Glu Met Arg Ala Tyr Trp Pro Asp Val Ile His Ser
50 55 60
Phe Pro Asn Arg Ser Arg Phe Trp Lys His Glu Trp Glu Lys His Gly
65 70 75 80
Thr Cys Ala Ala Gln Val Asp Ala Leu Asn Ser Gln Lys Lys Tyr Phe
85 90 95
Gly Arg Ser Leu Glu Leu Tyr Arg Glu Leu Asp Leu Asn Ser Val Leu
100 105 110
Leu Lys Leu Gly Ile Lys Pro Ser Ile Asn Tyr Tyr Gln Val Ala Asp
115 120 125
Phe Lys Asp Ala Leu Ala Arg Val Tyr Gly Val Ile Pro Lys Ile Gln
130 135 140
Cys Leu Pro Pro Ser Gln Asp Glu Glu Val Gln Thr Ile Gly Gln Ile
145 150 155 160
Glu Leu Cys Leu Thr Lys Gln Asp Gln Gln Leu Gln Asn Cys Thr Glu
165 170 175
Pro Gly Glu Gln Pro Ser Pro Lys Gln Glu Val Trp Leu Ala Asn Gly
180 185 190
Ala Ala Glu Ser Arg Gly Leu Arg Val Cys Glu Asp Gly Pro Val Phe
195 200 205
Tyr Pro Pro Pro Lys Lys Thr Lys His
210 215
<210> 29
<211> 183
<212> PRT
<213> 未知的
<220>
<223> RNA酶11
<400> 29
Glu Ala Ser Glu Ser Thr Met Lys Ile Ile Lys Glu Glu Phe Thr Asp
1 5 10 15
Glu Glu Met Gln Tyr Asp Met Ala Lys Ser Gly Gln Glu Lys Gln Thr
20 25 30
Ile Glu Ile Leu Met Asn Pro Ile Leu Leu Val Lys Asn Thr Ser Leu
35 40 45
Ser Met Ser Lys Asp Asp Met Ser Ser Thr Leu Leu Thr Phe Arg Ser
50 55 60
Leu His Tyr Asn Asp Pro Lys Gly Asn Ser Ser Gly Asn Asp Lys Glu
65 70 75 80
Cys Cys Asn Asp Met Thr Val Trp Arg Lys Val Ser Glu Ala Asn Gly
85 90 95
Ser Cys Lys Trp Ser Asn Asn Phe Ile Arg Ser Ser Thr Glu Val Met
100 105 110
Arg Arg Val His Arg Ala Pro Ser Cys Lys Phe Val Gln Asn Pro Gly
115 120 125
Ile Ser Cys Cys Glu Ser Leu Glu Leu Glu Asn Thr Val Cys Gln Phe
130 135 140
Thr Thr Gly Lys Gln Phe Pro Arg Cys Gln Tyr His Ser Val Thr Ser
145 150 155 160
Leu Glu Lys Ile Leu Thr Val Leu Thr Gly His Ser Leu Met Ser Trp
165 170 175
Leu Val Cys Gly Ser Lys Leu
180
<210> 30
<211> 185
<212> PRT
<213> 未知的
<220>
<223> RNA酶T2样蛋白
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> Xaa可以是任何天然存在的氨基酸
<400> 30
Xaa Leu Gly Gly Ala Asp Lys Arg Leu Arg Asp Asn His Glu Trp Lys
1 5 10 15
Lys Leu Ile Met Val Gln His Trp Pro Glu Thr Val Cys Glu Lys Ile
20 25 30
Gln Asn Asp Cys Arg Asp Pro Pro Asp Tyr Trp Thr Ile His Gly Leu
35 40 45
Trp Pro Asp Lys Ser Glu Gly Cys Asn Arg Ser Trp Pro Phe Asn Leu
50 55 60
Glu Glu Ile Lys Asp Leu Leu Pro Glu Met Arg Ala Tyr Trp Pro Asp
65 70 75 80
Val Ile His Ser Phe Pro Asn Arg Ser Arg Phe Trp Lys His Glu Trp
85 90 95
Glu Lys His Gly Thr Cys Ala Ala Gln Val Asp Ala Leu Asn Ser Gln
100 105 110
Lys Lys Tyr Phe Gly Arg Ser Leu Glu Leu Tyr Arg Glu Leu Asp Leu
115 120 125
Asn Ser Val Leu Leu Lys Leu Gly Ile Lys Pro Ser Ile Asn Tyr Tyr
130 135 140
Gln Thr Thr Glu Glu Asp Leu Asn Leu Asp Val Glu Pro Thr Thr Glu
145 150 155 160
Asp Thr Ala Glu Glu Val Thr Ile His Val Leu Leu His Ser Ala Leu
165 170 175
Phe Gly Glu Ile Gly Pro Arg Arg Trp
180 185
<210> 31
<211> 299
<212> PRT
<213> 未知的
<220>
<223> NOB1
<400> 31
Ala Pro Val Glu His Val Val Ala Asp Ala Gly Ala Phe Leu Arg His
1 5 10 15
Ala Ala Leu Gln Asp Ile Gly Lys Asn Ile Tyr Thr Ile Arg Glu Val
20 25 30
Val Thr Glu Ile Arg Asp Lys Ala Thr Arg Arg Arg Leu Ala Val Leu
35 40 45
Pro Tyr Glu Leu Arg Phe Lys Glu Pro Leu Pro Glu Tyr Val Arg Leu
50 55 60
Val Thr Glu Phe Ser Lys Lys Thr Gly Asp Tyr Pro Ser Leu Ser Ala
65 70 75 80
Thr Asp Ile Gln Val Leu Ala Leu Thr Tyr Gln Leu Glu Ala Glu Phe
85 90 95
Val Gly Val Ser His Leu Lys Gln Glu Pro Gln Lys Val Lys Val Ser
100 105 110
Ser Ser Ile Gln His Pro Glu Thr Pro Leu His Ile Ser Gly Phe His
115 120 125
Leu Pro Tyr Lys Pro Lys Pro Pro Gln Glu Thr Glu Lys Gly His Ser
130 135 140
Ala Cys Glu Pro Glu Asn Leu Glu Phe Ser Ser Phe Met Phe Trp Arg
145 150 155 160
Asn Pro Leu Pro Asn Ile Asp His Glu Leu Gln Glu Leu Leu Ile Asp
165 170 175
Arg Gly Glu Asp Val Pro Ser Glu Glu Glu Glu Glu Glu Glu Asn Gly
180 185 190
Phe Glu Asp Arg Lys Asp Asp Ser Asp Asp Asp Gly Gly Gly Trp Ile
195 200 205
Thr Pro Ser Asn Ile Lys Gln Ile Gln Gln Glu Leu Glu Gln Cys Asp
210 215 220
Val Pro Glu Asp Val Arg Val Gly Cys Leu Thr Thr Asp Phe Ala Met
225 230 235 240
Gln Asn Val Leu Leu Gln Met Gly Leu His Val Leu Ala Val Asn Gly
245 250 255
Met Leu Ile Arg Glu Ala Arg Ser Tyr Ile Leu Arg Cys His Gly Cys
260 265 270
Phe Lys Thr Thr Ser Asp Met Ser Arg Val Phe Cys Ser His Cys Gly
275 280 285
Asn Lys Thr Leu Lys Lys Val Ser Val Thr Val
290 295
<210> 32
<211> 210
<212> PRT
<213> 未知的
<220>
<223> ENDOV
<400> 32
Ala Phe Ser Gly Leu Gln Arg Val Gly Gly Val Asp Val Ser Phe Val
1 5 10 15
Lys Gly Asp Ser Val Arg Ala Cys Ala Ser Leu Val Val Leu Ser Phe
20 25 30
Pro Glu Leu Glu Val Val Tyr Glu Glu Ser Arg Met Val Ser Leu Thr
35 40 45
Ala Pro Tyr Val Ser Gly Phe Leu Ala Phe Arg Glu Val Pro Phe Leu
50 55 60
Leu Glu Leu Val Gln Gln Leu Arg Glu Lys Glu Pro Gly Leu Met Pro
65 70 75 80
Gln Val Leu Leu Val Asp Gly Asn Gly Val Leu His His Arg Gly Phe
85 90 95
Gly Val Ala Cys His Leu Gly Val Leu Thr Asp Leu Pro Cys Val Gly
100 105 110
Val Ala Lys Lys Leu Leu Gln Val Asp Gly Leu Glu Asn Asn Ala Leu
115 120 125
His Lys Glu Lys Ile Arg Leu Leu Gln Thr Arg Gly Asp Ser Phe Pro
130 135 140
Leu Leu Gly Asp Ser Gly Thr Val Leu Gly Met Ala Leu Arg Ser His
145 150 155 160
Asp Arg Ser Thr Arg Pro Leu Tyr Ile Ser Val Gly His Arg Met Ser
165 170 175
Leu Glu Ala Ala Val Arg Leu Thr Cys Cys Cys Cys Arg Phe Arg Ile
180 185 190
Pro Glu Pro Val Arg Gln Ala Asp Ile Cys Ser Arg Glu His Ile Arg
195 200 205
Lys Ser
210
<210> 33
<211> 249
<212> PRT
<213> 未知的
<220>
<223> ENDOG
<400> 33
Ala Glu Leu Pro Pro Val Pro Gly Gly Pro Arg Gly Pro Gly Glu Leu
1 5 10 15
Ala Lys Tyr Gly Leu Pro Gly Leu Ala Gln Leu Lys Ser Arg Glu Ser
20 25 30
Tyr Val Leu Cys Tyr Asp Pro Arg Thr Arg Gly Ala Leu Trp Val Val
35 40 45
Glu Gln Leu Arg Pro Glu Arg Leu Arg Gly Asp Gly Asp Arg Arg Glu
50 55 60
Cys Asp Phe Arg Glu Asp Asp Ser Val His Ala Tyr His Arg Ala Thr
65 70 75 80
Asn Ala Asp Tyr Arg Gly Ser Gly Phe Asp Arg Gly His Leu Ala Ala
85 90 95
Ala Ala Asn His Arg Trp Ser Gln Lys Ala Met Asp Asp Thr Phe Tyr
100 105 110
Leu Ser Asn Val Ala Pro Gln Val Pro His Leu Asn Gln Asn Ala Trp
115 120 125
Asn Asn Leu Glu Lys Tyr Ser Arg Ser Leu Thr Arg Ser Tyr Gln Asn
130 135 140
Val Tyr Val Cys Thr Gly Pro Leu Phe Leu Pro Arg Thr Glu Ala Asp
145 150 155 160
Gly Lys Ser Tyr Val Lys Tyr Gln Val Ile Gly Lys Asn His Val Ala
165 170 175
Val Pro Thr His Phe Phe Lys Val Leu Ile Leu Glu Ala Ala Gly Gly
180 185 190
Gln Ile Glu Leu Arg Thr Tyr Val Met Pro Asn Ala Pro Val Asp Glu
195 200 205
Ala Ile Pro Leu Glu Arg Phe Leu Val Pro Ile Glu Ser Ile Glu Arg
210 215 220
Ala Ser Gly Leu Leu Phe Val Pro Asn Ile Leu Ala Arg Ala Gly Ser
225 230 235 240
Leu Lys Ala Ile Thr Ala Gly Ser Lys
245
<210> 34
<211> 479
<212> PRT
<213> 未知的
<220>
<223> ENDOD1
<400> 34
Arg Leu Val Gly Glu Glu Glu Ala Gly Phe Gly Glu Cys Asp Lys Phe
1 5 10 15
Phe Tyr Ala Gly Thr Pro Pro Ala Gly Leu Ala Ala Asp Ser His Val
20 25 30
Lys Ile Cys Gln Arg Ala Glu Gly Ala Glu Arg Phe Ala Thr Leu Tyr
35 40 45
Ser Thr Arg Asp Arg Ile Pro Val Tyr Ser Ala Phe Arg Ala Pro Arg
50 55 60
Pro Ala Pro Gly Gly Ala Glu Gln Arg Trp Leu Val Glu Pro Gln Ile
65 70 75 80
Asp Asp Pro Asn Ser Asn Leu Glu Glu Ala Ile Asn Glu Ala Glu Ala
85 90 95
Ile Thr Ser Val Asn Ser Leu Gly Ser Lys Gln Ala Leu Asn Thr Asp
100 105 110
Tyr Leu Asp Ser Asp Tyr Gln Arg Gly Gln Leu Tyr Pro Phe Ser Leu
115 120 125
Ser Ser Asp Val Gln Val Ala Thr Phe Thr Leu Thr Asn Ser Ala Pro
130 135 140
Met Thr Gln Ser Phe Gln Glu Arg Trp Tyr Val Asn Leu His Ser Leu
145 150 155 160
Met Asp Arg Ala Leu Thr Pro Gln Cys Gly Ser Gly Glu Asp Leu Tyr
165 170 175
Ile Leu Thr Gly Thr Val Pro Ser Asp Tyr Arg Val Lys Asp Lys Val
180 185 190
Ala Val Pro Glu Phe Val Trp Leu Ala Ala Cys Cys Ala Val Pro Gly
195 200 205
Gly Gly Trp Ala Met Gly Phe Val Lys His Thr Arg Asp Ser Asp Ile
210 215 220
Ile Glu Asp Val Met Val Lys Asp Leu Gln Lys Leu Leu Pro Phe Asn
225 230 235 240
Pro Gln Leu Phe Gln Asn Asn Cys Gly Glu Thr Glu Gln Asp Thr Glu
245 250 255
Lys Met Lys Lys Ile Leu Glu Val Val Asn Gln Ile Gln Asp Glu Glu
260 265 270
Arg Met Val Gln Ser Gln Lys Ser Ser Ser Pro Leu Ser Ser Thr Arg
275 280 285
Ser Lys Arg Ser Thr Leu Leu Pro Pro Glu Ala Ser Glu Gly Ser Ser
290 295 300
Ser Phe Leu Gly Lys Leu Met Gly Phe Ile Ala Thr Pro Phe Ile Lys
305 310 315 320
Leu Phe Gln Leu Ile Tyr Tyr Leu Val Val Ala Ile Leu Lys Asn Ile
325 330 335
Val Tyr Phe Leu Trp Cys Val Thr Lys Gln Val Ile Asn Gly Ile Glu
340 345 350
Ser Cys Leu Tyr Arg Leu Gly Ser Ala Thr Ile Ser Tyr Phe Met Ala
355 360 365
Ile Gly Glu Glu Leu Val Ser Ile Pro Trp Lys Val Leu Lys Val Val
370 375 380
Ala Lys Val Ile Arg Ala Leu Leu Arg Ile Leu Cys Cys Leu Leu Lys
385 390 395 400
Ala Ile Cys Arg Val Leu Ser Ile Pro Val Arg Val Leu Val Asp Val
405 410 415
Ala Thr Phe Pro Val Tyr Thr Met Gly Ala Ile Pro Ile Val Cys Lys
420 425 430
Asp Ile Ala Leu Gly Leu Gly Gly Thr Val Ser Leu Leu Phe Asp Thr
435 440 445
Ala Phe Gly Thr Leu Gly Gly Leu Phe Gln Val Val Phe Ser Val Cys
450 455 460
Lys Arg Ile Gly Tyr Lys Val Thr Phe Asp Asn Ser Gly Glu Leu
465 470 475
<210> 35
<211> 380
<212> PRT
<213> 未知的
<220>
<223> hFEN1
<400> 35
Met Gly Ile Gln Gly Leu Ala Lys Leu Ile Ala Asp Val Ala Pro Ser
1 5 10 15
Ala Ile Arg Glu Asn Asp Ile Lys Ser Tyr Phe Gly Arg Lys Val Ala
20 25 30
Ile Asp Ala Ser Met Ser Ile Tyr Gln Phe Leu Ile Ala Val Arg Gln
35 40 45
Gly Gly Asp Val Leu Gln Asn Glu Glu Gly Glu Thr Thr Ser His Leu
50 55 60
Met Gly Met Phe Tyr Arg Thr Ile Arg Met Met Glu Asn Gly Ile Lys
65 70 75 80
Pro Val Tyr Val Phe Asp Gly Lys Pro Pro Gln Leu Lys Ser Gly Glu
85 90 95
Leu Ala Lys Arg Ser Glu Arg Arg Ala Glu Ala Glu Lys Gln Leu Gln
100 105 110
Gln Ala Gln Ala Ala Gly Ala Glu Gln Glu Val Glu Lys Phe Thr Lys
115 120 125
Arg Leu Val Lys Val Thr Lys Gln His Asn Asp Glu Cys Lys His Leu
130 135 140
Leu Ser Leu Met Gly Ile Pro Tyr Leu Asp Ala Pro Ser Glu Ala Glu
145 150 155 160
Ala Ser Cys Ala Ala Leu Val Lys Ala Gly Lys Val Tyr Ala Ala Ala
165 170 175
Thr Glu Asp Met Asp Cys Leu Thr Phe Gly Ser Pro Val Leu Met Arg
180 185 190
His Leu Thr Ala Ser Glu Ala Lys Lys Leu Pro Ile Gln Glu Phe His
195 200 205
Leu Ser Arg Ile Leu Gln Glu Leu Gly Leu Asn Gln Glu Gln Phe Val
210 215 220
Asp Leu Cys Ile Leu Leu Gly Ser Asp Tyr Cys Glu Ser Ile Arg Gly
225 230 235 240
Ile Gly Pro Lys Arg Ala Val Asp Leu Ile Gln Lys His Lys Ser Ile
245 250 255
Glu Glu Ile Val Arg Arg Leu Asp Pro Asn Lys Tyr Pro Val Pro Glu
260 265 270
Asn Trp Leu His Lys Glu Ala His Gln Leu Phe Leu Glu Pro Glu Val
275 280 285
Leu Asp Pro Glu Ser Val Glu Leu Lys Trp Ser Glu Pro Asn Glu Glu
290 295 300
Glu Leu Ile Lys Phe Met Cys Gly Glu Lys Gln Phe Ser Glu Glu Arg
305 310 315 320
Ile Arg Ser Gly Val Lys Arg Leu Ser Lys Ser Arg Gln Gly Ser Thr
325 330 335
Gln Gly Arg Leu Asp Asp Phe Phe Lys Val Thr Gly Ser Leu Ser Ser
340 345 350
Ala Lys Arg Lys Glu Pro Glu Pro Lys Gly Ser Thr Lys Lys Lys Ala
355 360 365
Lys Thr Gly Ala Ala Gly Lys Phe Lys Arg Gly Lys
370 375 380
<210> 36
<211> 186
<212> PRT
<213> 智人（Homo Sapiens）
<400> 36
Glu Ser Thr His Val Glu Phe Lys Arg Phe Thr Thr Lys Lys Val Ile
1 5 10 15
Pro Arg Ile Lys Glu Met Leu Pro His Tyr Val Ser Ala Phe Ala Asn
20 25 30
Thr Gln Gly Gly Tyr Val Leu Ile Gly Val Asp Asp Lys Ser Lys Glu
35 40 45
Val Val Gly Cys Lys Trp Glu Lys Val Asn Pro Asp Leu Leu Lys Lys
50 55 60
Glu Ile Glu Asn Cys Ile Glu Lys Leu Pro Thr Phe His Phe Cys Cys
65 70 75 80
Glu Lys Pro Lys Val Asn Phe Thr Thr Lys Ile Leu Asn Val Tyr Gln
85 90 95
Lys Asp Val Leu Asp Gly Tyr Val Cys Val Ile Gln Val Glu Pro Phe
100 105 110
Cys Cys Val Val Phe Ala Glu Ala Pro Asp Ser Trp Ile Met Lys Asp
115 120 125
Asn Ser Val Thr Arg Leu Thr Ala Glu Gln Trp Val Val Met Met Leu
130 135 140
Asp Thr Gln Ser Ala Pro Pro Ser Leu Val Thr Asp Tyr Asn Ser Cys
145 150 155 160
Leu Ile Ser Ser Ala Ser Ser Ala Arg Lys Ser Pro Gly Tyr Pro Ile
165 170 175
Lys Val His Lys Phe Lys Glu Ala Leu Gln
180 185
<210> 37
<211> 262
<212> PRT
<213> 智人（Homo Sapiens）
<400> 37
Thr Leu Gln Gly Thr Asn Thr Tyr Leu Val Gly Thr Gly Pro Arg Arg
1 5 10 15
Ile Leu Ile Asp Thr Gly Glu Pro Ala Ile Pro Glu Tyr Ile Ser Cys
20 25 30
Leu Lys Gln Ala Leu Thr Glu Phe Asn Thr Ala Ile Gln Glu Ile Val
35 40 45
Val Thr His Trp His Arg Asp His Ser Gly Gly Ile Gly Asp Ile Cys
50 55 60
Lys Ser Ile Asn Asn Asp Thr Thr Tyr Cys Ile Lys Lys Leu Pro Arg
65 70 75 80
Asn Pro Gln Arg Glu Glu Ile Ile Gly Asn Gly Glu Gln Gln Tyr Val
85 90 95
Tyr Leu Lys Asp Gly Asp Val Ile Lys Thr Glu Gly Ala Thr Leu Arg
100 105 110
Val Leu Tyr Thr Pro Gly His Thr Asp Asp His Met Ala Leu Leu Leu
115 120 125
Glu Glu Glu Asn Ala Ile Phe Ser Gly Asp Cys Ile Leu Gly Glu Gly
130 135 140
Thr Thr Val Phe Glu Asp Leu Tyr Asp Tyr Met Asn Ser Leu Lys Glu
145 150 155 160
Leu Leu Lys Ile Lys Ala Asp Ile Ile Tyr Pro Gly His Gly Pro Val
165 170 175
Ile His Asn Ala Glu Ala Lys Ile Gln Gln Tyr Ile Ser His Arg Asn
180 185 190
Ile Arg Glu Gln Gln Ile Leu Thr Leu Phe Arg Glu Asn Phe Glu Lys
195 200 205
Ser Phe Thr Val Met Glu Leu Val Lys Ile Ile Tyr Lys Asn Thr Pro
210 215 220
Glu Asn Leu His Glu Met Ala Lys His Asn Leu Leu Leu His Leu Lys
225 230 235 240
Lys Leu Glu Lys Glu Gly Lys Ile Phe Ser Asn Thr Asp Pro Asp Lys
245 250 255
Lys Trp Lys Ala His Leu
260
<210> 38
<211> 518
<212> PRT
<213> 智人（Homo Sapiens）
<400> 38
Met Leu Arg Val Val Ser Trp Asn Ile Asn Gly Ile Arg Arg Pro Leu
1 5 10 15
Gln Gly Val Ala Asn Gln Glu Pro Ser Asn Cys Ala Ala Val Ala Val
20 25 30
Gly Arg Ile Leu Asp Glu Leu Asp Ala Asp Ile Val Cys Leu Gln Glu
35 40 45
Thr Lys Val Thr Arg Asp Ala Leu Thr Glu Pro Leu Ala Ile Val Glu
50 55 60
Gly Tyr Asn Ser Tyr Phe Ser Phe Ser Arg Asn Arg Ser Gly Tyr Ser
65 70 75 80
Gly Val Ala Thr Phe Cys Lys Asp Asn Ala Thr Pro Val Ala Ala Glu
85 90 95
Glu Gly Leu Ser Gly Leu Phe Ala Thr Gln Asn Gly Asp Val Gly Cys
100 105 110
Tyr Gly Asn Met Asp Glu Phe Thr Gln Glu Glu Leu Arg Ala Leu Asp
115 120 125
Ser Glu Gly Arg Ala Leu Leu Thr Gln His Lys Ile Arg Thr Trp Glu
130 135 140
Gly Lys Glu Lys Thr Leu Thr Leu Ile Asn Val Tyr Cys Pro His Ala
145 150 155 160
Asp Pro Gly Arg Pro Glu Arg Leu Val Phe Lys Met Arg Phe Tyr Arg
165 170 175
Leu Leu Gln Ile Arg Ala Glu Ala Leu Leu Ala Ala Gly Ser His Val
180 185 190
Ile Ile Leu Gly Asp Leu Asn Thr Ala His Arg Pro Ile Asp His Trp
195 200 205
Asp Ala Val Asn Leu Glu Cys Phe Glu Glu Asp Pro Gly Arg Lys Trp
210 215 220
Met Asp Ser Leu Leu Ser Asn Leu Gly Cys Gln Ser Ala Ser His Val
225 230 235 240
Gly Pro Phe Ile Asp Ser Tyr Arg Cys Phe Gln Pro Lys Gln Glu Gly
245 250 255
Ala Phe Thr Cys Trp Ser Ala Val Thr Gly Ala Arg His Leu Asn Tyr
260 265 270
Gly Ser Arg Leu Asp Tyr Val Leu Gly Asp Arg Thr Leu Val Ile Asp
275 280 285
Thr Phe Gln Ala Ser Phe Leu Leu Pro Glu Val Met Gly Ser Asp His
290 295 300
Cys Pro Val Gly Ala Val Leu Ser Val Ser Ser Val Pro Ala Lys Gln
305 310 315 320
Cys Pro Pro Leu Cys Thr Arg Phe Leu Pro Glu Phe Ala Gly Thr Gln
325 330 335
Leu Lys Ile Leu Arg Phe Leu Val Pro Leu Glu Gln Ser Pro Val Leu
340 345 350
Glu Gln Ser Thr Leu Gln His Asn Asn Gln Thr Arg Val Gln Thr Cys
355 360 365
Gln Asn Lys Ala Gln Val Arg Ser Thr Arg Pro Gln Pro Ser Gln Val
370 375 380
Gly Ser Ser Arg Gly Gln Lys Asn Leu Lys Ser Tyr Phe Gln Pro Ser
385 390 395 400
Pro Ser Cys Pro Gln Ala Ser Pro Asp Ile Glu Leu Pro Ser Leu Pro
405 410 415
Leu Met Ser Ala Leu Met Thr Pro Lys Thr Pro Glu Glu Lys Ala Val
420 425 430
Ala Lys Val Val Lys Gly Gln Ala Lys Thr Ser Glu Ala Lys Asp Glu
435 440 445
Lys Glu Leu Arg Thr Ser Phe Trp Lys Ser Val Leu Ala Gly Pro Leu
450 455 460
Arg Thr Pro Leu Cys Gly Gly His Arg Glu Pro Cys Val Met Arg Thr
465 470 475 480
Val Lys Lys Pro Gly Pro Asn Leu Gly Arg Arg Phe Tyr Met Cys Ala
485 490 495
Arg Pro Arg Gly Pro Pro Thr Asp Pro Ser Ser Arg Cys Asn Phe Phe
500 505 510
Leu Trp Ser Arg Pro Ser
515
<210> 39
<211> 350
<212> PRT
<213> 智人（Homo Sapiens）
<400> 39
Met Leu Arg Val Val Ser Trp Asn Ile Asn Gly Ile Arg Arg Pro Leu
1 5 10 15
Gln Gly Val Ala Asn Gln Glu Pro Ser Asn Cys Ala Ala Val Ala Val
20 25 30
Gly Arg Ile Leu Asp Glu Leu Asp Ala Asp Ile Val Cys Leu Gln Glu
35 40 45
Thr Lys Val Thr Arg Asp Ala Leu Thr Glu Pro Leu Ala Ile Val Glu
50 55 60
Gly Tyr Asn Ser Tyr Phe Ser Phe Ser Arg Asn Arg Ser Gly Tyr Ser
65 70 75 80
Gly Val Ala Thr Phe Cys Lys Asp Asn Ala Thr Pro Val Ala Ala Glu
85 90 95
Glu Gly Leu Ser Gly Leu Phe Ala Thr Gln Asn Gly Asp Val Gly Cys
100 105 110
Tyr Gly Asn Met Asp Glu Phe Thr Gln Glu Glu Leu Arg Ala Leu Asp
115 120 125
Ser Glu Gly Arg Ala Leu Leu Thr Gln His Lys Ile Arg Thr Trp Glu
130 135 140
Gly Lys Glu Lys Thr Leu Thr Leu Ile Asn Val Tyr Cys Pro His Ala
145 150 155 160
Asp Pro Gly Arg Pro Glu Arg Leu Val Phe Lys Met Arg Phe Tyr Arg
165 170 175
Leu Leu Gln Ile Arg Ala Glu Ala Leu Leu Ala Ala Gly Ser His Val
180 185 190
Ile Ile Leu Gly Asp Leu Asn Thr Ala His Arg Pro Ile Asp His Trp
195 200 205
Asp Ala Val Asn Leu Glu Cys Phe Glu Glu Asp Pro Gly Arg Lys Trp
210 215 220
Met Asp Ser Leu Leu Ser Asn Leu Gly Cys Gln Ser Ala Ser His Val
225 230 235 240
Gly Pro Phe Ile Asp Ser Tyr Arg Cys Phe Gln Pro Lys Gln Glu Gly
245 250 255
Ala Phe Thr Cys Trp Ser Ala Val Thr Gly Ala Arg His Leu Asn Tyr
260 265 270
Gly Ser Arg Leu Asp Tyr Val Leu Gly Asp Arg Thr Leu Val Ile Asp
275 280 285
Thr Phe Gln Ala Ser Phe Leu Leu Pro Glu Val Met Gly Ser Asp His
290 295 300
Cys Pro Val Gly Ala Val Leu Ser Val Ser Ser Val Pro Ala Lys Gln
305 310 315 320
Cys Pro Pro Leu Cys Thr Arg Phe Leu Pro Glu Phe Ala Gly Thr Gln
325 330 335
Leu Lys Ile Leu Arg Phe Leu Val Pro Leu Glu Gln Ser Pro
340 345 350
<210> 40
<211> 123
<212> PRT
<213> 智人（Homo Sapiens）
<400> 40
Gln Asp Asn Ser Arg Tyr Thr His Phe Leu Thr Gln His Tyr Asp Ala
1 5 10 15
Lys Pro Gln Gly Arg Asp Asp Arg Tyr Cys Glu Ser Ile Met Arg Arg
20 25 30
Arg Gly Leu Thr Ser Pro Cys Lys Asp Ile Asn Thr Phe Ile His Gly
35 40 45
Asn Lys Arg Ser Ile Lys Ala Ile Cys Glu Asn Lys Asn Gly Asn Pro
50 55 60
His Arg Glu Asn Leu Arg Ile Ser Lys Ser Ser Phe Gln Val Thr Thr
65 70 75 80
Cys Lys Leu His Gly Gly Ser Pro Trp Pro Pro Cys Gln Tyr Arg Ala
85 90 95
Thr Ala Gly Phe Arg Asn Val Val Val Ala Cys Glu Asn Gly Leu Pro
100 105 110
Val His Leu Asp Gln Ser Ile Phe Arg Arg Pro
115 120
<210> 41
<211> 136
<212> PRT
<213> 智人（Homo Sapiens）
<400> 41
Ser Ser Leu Ile Arg Arg Val Ile Ser Thr Ala Lys Ala Pro Gly Ala
1 5 10 15
Ile Gly Pro Tyr Ser Gln Ala Val Leu Val Asp Arg Thr Ile Tyr Ile
20 25 30
Ser Gly Gln Ile Gly Met Asp Pro Ser Ser Gly Gln Leu Val Ser Gly
35 40 45
Gly Val Ala Glu Glu Ala Lys Gln Ala Leu Lys Asn Met Gly Glu Ile
50 55 60
Leu Lys Ala Ala Gly Cys Asp Phe Thr Asn Val Val Lys Thr Thr Val
65 70 75 80
Leu Leu Ala Asp Ile Asn Asp Phe Asn Thr Val Asn Glu Ile Tyr Lys
85 90 95
Gln Tyr Phe Lys Ser Asn Phe Pro Ala Arg Ala Ala Tyr Gln Val Ala
100 105 110
Ala Leu Pro Lys Gly Ser Arg Ile Glu Ile Glu Ala Val Ala Ile Gln
115 120 125
Gly Pro Leu Thr Thr Ala Ser Leu
130 135
<210> 42
<211> 189
<212> PRT
<213> 智人（Homo Sapiens）
<400> 42
Gly Gly Gly Thr Pro Lys Ala Pro Asn Leu Glu Pro Pro Leu Pro Glu
1 5 10 15
Glu Glu Lys Glu Gly Ser Asp Leu Arg Pro Val Val Ile Asp Gly Ser
20 25 30
Asn Val Ala Met Ser His Gly Asn Lys Glu Val Phe Ser Cys Arg Gly
35 40 45
Ile Leu Leu Ala Val Asn Trp Phe Leu Glu Arg Gly His Thr Asp Ile
50 55 60
Thr Val Phe Val Pro Ser Trp Arg Lys Glu Gln Pro Arg Pro Asp Val
65 70 75 80
Pro Ile Thr Asp Gln His Ile Leu Arg Glu Leu Glu Lys Lys Lys Ile
85 90 95
Leu Val Phe Thr Pro Ser Arg Arg Val Gly Gly Lys Arg Val Val Cys
100 105 110
Tyr Asp Asp Arg Phe Ile Val Lys Leu Ala Tyr Glu Ser Asp Gly Ile
115 120 125
Val Val Ser Asn Asp Thr Tyr Arg Asp Leu Gln Gly Glu Arg Gln Glu
130 135 140
Trp Lys Arg Phe Ile Glu Glu Arg Leu Leu Met Tyr Ser Phe Val Asn
145 150 155 160
Asp Lys Phe Met Pro Pro Asp Asp Pro Leu Gly Arg His Gly Pro Ser
165 170 175
Leu Asp Asn Phe Leu Arg Lys Lys Pro Leu Thr Leu Glu
180 185
<210> 43
<211> 598
<212> PRT
<213> 智人（Homo Sapiens）
<400> 43
Ser Gly Pro Cys Gly Glu Lys Pro Val Leu Glu Ala Ser Pro Thr Met
1 5 10 15
Ser Leu Trp Glu Phe Glu Asp Ser His Ser Arg Gln Gly Thr Pro Arg
20 25 30
Pro Gly Gln Glu Leu Ala Ala Glu Glu Ala Ser Ala Leu Glu Leu Gln
35 40 45
Met Lys Val Asp Phe Phe Arg Lys Leu Gly Tyr Ser Ser Thr Glu Ile
50 55 60
His Ser Val Leu Gln Lys Leu Gly Val Gln Ala Asp Thr Asn Thr Val
65 70 75 80
Leu Gly Glu Leu Val Lys His Gly Thr Ala Thr Glu Arg Glu Arg Gln
85 90 95
Thr Ser Pro Asp Pro Cys Pro Gln Leu Pro Leu Val Pro Arg Gly Gly
100 105 110
Gly Thr Pro Lys Ala Pro Asn Leu Glu Pro Pro Leu Pro Glu Glu Glu
115 120 125
Lys Glu Gly Ser Asp Leu Arg Pro Val Val Ile Asp Gly Ser Asn Val
130 135 140
Ala Met Ser His Gly Asn Lys Glu Val Phe Ser Cys Arg Gly Ile Leu
145 150 155 160
Leu Ala Val Asn Trp Phe Leu Glu Arg Gly His Thr Asp Ile Thr Val
165 170 175
Phe Val Pro Ser Trp Arg Lys Glu Gln Pro Arg Pro Asp Val Pro Ile
180 185 190
Thr Asp Gln His Ile Leu Arg Glu Leu Glu Lys Lys Lys Ile Leu Val
195 200 205
Phe Thr Pro Ser Arg Arg Val Gly Gly Lys Arg Val Val Cys Tyr Asp
210 215 220
Asp Arg Phe Ile Val Lys Leu Ala Tyr Glu Ser Asp Gly Ile Val Val
225 230 235 240
Ser Asn Asp Thr Tyr Arg Asp Leu Gln Gly Glu Arg Gln Glu Trp Lys
245 250 255
Arg Phe Ile Glu Glu Arg Leu Leu Met Tyr Ser Phe Val Asn Asp Lys
260 265 270
Phe Met Pro Pro Asp Asp Pro Leu Gly Arg His Gly Pro Ser Leu Asp
275 280 285
Asn Phe Leu Arg Lys Lys Pro Leu Thr Leu Glu His Arg Lys Gln Pro
290 295 300
Cys Pro Tyr Gly Arg Lys Cys Thr Tyr Gly Ile Lys Cys Arg Phe Phe
305 310 315 320
His Pro Glu Arg Pro Ser Cys Pro Gln Arg Ser Val Ala Asp Glu Leu
325 330 335
Arg Ala Asn Ala Leu Leu Ser Pro Pro Arg Ala Pro Ser Lys Asp Lys
340 345 350
Asn Gly Arg Arg Pro Ser Pro Ser Ser Gln Ser Ser Ser Leu Leu Thr
355 360 365
Glu Ser Glu Gln Cys Ser Leu Asp Gly Lys Lys Leu Gly Ala Gln Ala
370 375 380
Ser Pro Gly Ser Arg Gln Glu Gly Leu Thr Gln Thr Tyr Ala Pro Ser
385 390 395 400
Gly Arg Ser Leu Ala Pro Ser Gly Gly Ser Gly Ser Ser Phe Gly Pro
405 410 415
Thr Asp Trp Leu Pro Gln Thr Leu Asp Ser Leu Pro Tyr Val Ser Gln
420 425 430
Asp Cys Leu Asp Ser Gly Ile Gly Ser Leu Glu Ser Gln Met Ser Glu
435 440 445
Leu Trp Gly Val Arg Gly Gly Gly Pro Gly Glu Pro Gly Pro Pro Arg
450 455 460
Ala Pro Tyr Thr Gly Tyr Ser Pro Tyr Gly Ser Glu Leu Pro Ala Thr
465 470 475 480
Ala Ala Phe Ser Ala Phe Gly Arg Ala Met Gly Ala Gly His Phe Ser
485 490 495
Val Pro Ala Asp Tyr Pro Pro Ala Pro Pro Ala Phe Pro Pro Arg Glu
500 505 510
Tyr Trp Ser Glu Pro Tyr Pro Leu Pro Pro Pro Thr Ser Val Leu Gln
515 520 525
Glu Pro Pro Val Gln Ser Pro Gly Ala Gly Arg Ser Pro Trp Gly Arg
530 535 540
Ala Gly Ser Leu Ala Lys Glu Gln Ala Ser Val Tyr Thr Lys Leu Cys
545 550 555 560
Gly Val Phe Pro Pro His Leu Val Glu Ala Val Met Gly Arg Phe Pro
565 570 575
Gln Leu Leu Asp Pro Gln Gln Leu Ala Ala Glu Ile Leu Ser Tyr Lys
580 585 590
Ser Gln His Pro Ser Glu
595
<210> 44
<211> 136
<212> PRT
<213> 智人（Homo Sapiens）
<400> 44
Ser Ser Leu Ile Arg Arg Val Ile Ser Thr Ala Lys Ala Pro Gly Ala
1 5 10 15
Ile Gly Pro Tyr Ser Gln Ala Val Leu Val Asp Arg Thr Ile Tyr Ile
20 25 30
Ser Gly Gln Ile Gly Met Asp Pro Ser Ser Gly Gln Leu Val Ser Gly
35 40 45
Gly Val Ala Glu Glu Ala Lys Gln Ala Leu Lys Asn Met Gly Glu Ile
50 55 60
Leu Lys Ala Ala Gly Cys Asp Phe Thr Asn Val Val Lys Thr Thr Val
65 70 75 80
Leu Leu Ala Asp Ile Asn Asp Phe Asn Thr Val Asn Glu Ile Tyr Lys
85 90 95
Gln Tyr Phe Lys Ser Asn Phe Pro Ala Arg Ala Ala Tyr Gln Val Ala
100 105 110
Ala Leu Pro Lys Gly Ser Arg Ile Glu Ile Glu Ala Val Ala Ile Gln
115 120 125
Gly Pro Leu Thr Thr Ala Ser Leu
130 135
<210> 45
<211> 966
<212> PRT
<213> 生黄瘤胃球菌（Ruminococcus flavefaciens）
<400> 45
Ile Glu Lys Lys Lys Ser Phe Ala Lys Gly Met Gly Val Lys Ser Thr
1 5 10 15
Leu Val Ser Gly Ser Lys Val Tyr Met Thr Thr Phe Ala Glu Gly Ser
20 25 30
Asp Ala Arg Leu Glu Lys Ile Val Glu Gly Asp Ser Ile Arg Ser Val
35 40 45
Asn Glu Gly Glu Ala Phe Ser Ala Glu Met Ala Asp Lys Asn Ala Gly
50 55 60
Tyr Lys Ile Gly Asn Ala Lys Phe Ser His Pro Lys Gly Tyr Ala Val
65 70 75 80
Val Ala Asn Asn Pro Leu Tyr Thr Gly Pro Val Gln Gln Asp Met Leu
85 90 95
Gly Leu Lys Glu Thr Leu Glu Lys Arg Tyr Phe Gly Glu Ser Ala Asp
100 105 110
Gly Asn Asp Asn Ile Cys Ile Gln Val Ile His Asn Ile Leu Asp Ile
115 120 125
Glu Lys Ile Leu Ala Glu Tyr Ile Thr Asn Ala Ala Tyr Ala Val Asn
130 135 140
Asn Ile Ser Gly Leu Asp Lys Asp Ile Ile Gly Phe Gly Lys Phe Ser
145 150 155 160
Thr Val Tyr Thr Tyr Asp Glu Phe Lys Asp Pro Glu His His Arg Ala
165 170 175
Ala Phe Asn Asn Asn Asp Lys Leu Ile Asn Ala Ile Lys Ala Gln Tyr
180 185 190
Asp Glu Phe Asp Asn Phe Leu Asp Asn Pro Arg Leu Gly Tyr Phe Gly
195 200 205
Gln Ala Phe Phe Ser Lys Glu Gly Arg Asn Tyr Ile Ile Asn Tyr Gly
210 215 220
Asn Glu Cys Tyr Asp Ile Leu Ala Leu Leu Ser Gly Leu Ala His Trp
225 230 235 240
Val Val Ala Asn Asn Glu Glu Glu Ser Arg Ile Ser Arg Thr Trp Leu
245 250 255
Tyr Asn Leu Asp Lys Asn Leu Asp Asn Glu Tyr Ile Ser Thr Leu Asn
260 265 270
Tyr Leu Tyr Asp Arg Ile Thr Asn Glu Leu Thr Asn Ser Phe Ser Lys
275 280 285
Asn Ser Ala Ala Asn Val Asn Tyr Ile Ala Glu Thr Leu Gly Ile Asn
290 295 300
Pro Ala Glu Phe Ala Glu Gln Tyr Phe Arg Phe Ser Ile Met Lys Glu
305 310 315 320
Gln Lys Asn Leu Gly Phe Asn Ile Thr Lys Leu Arg Glu Val Met Leu
325 330 335
Asp Arg Lys Asp Met Ser Glu Ile Arg Lys Asn His Lys Val Phe Asp
340 345 350
Ser Ile Arg Thr Lys Val Tyr Thr Met Met Asp Phe Val Ile Tyr Arg
355 360 365
Tyr Tyr Ile Glu Glu Asp Ala Lys Val Ala Ala Ala Asn Lys Ser Leu
370 375 380
Pro Asp Asn Glu Lys Ser Leu Ser Glu Lys Asp Ile Phe Val Ile Asn
385 390 395 400
Leu Arg Gly Ser Phe Asn Asp Asp Gln Lys Asp Ala Leu Tyr Tyr Asp
405 410 415
Glu Ala Asn Arg Ile Trp Arg Lys Leu Glu Asn Ile Met His Asn Ile
420 425 430
Lys Glu Phe Arg Gly Asn Lys Thr Arg Glu Tyr Lys Lys Lys Asp Ala
435 440 445
Pro Arg Leu Pro Arg Ile Leu Pro Ala Gly Arg Asp Val Ser Ala Phe
450 455 460
Ser Lys Leu Met Tyr Ala Leu Thr Met Phe Leu Asp Gly Lys Glu Ile
465 470 475 480
Asn Asp Leu Leu Thr Thr Leu Ile Asn Lys Phe Asp Asn Ile Gln Ser
485 490 495
Phe Leu Lys Val Met Pro Leu Ile Gly Val Asn Ala Lys Phe Val Glu
500 505 510
Glu Tyr Ala Phe Phe Lys Asp Ser Ala Lys Ile Ala Asp Glu Leu Arg
515 520 525
Leu Ile Lys Ser Phe Ala Arg Met Gly Glu Pro Ile Ala Asp Ala Arg
530 535 540
Arg Ala Met Tyr Ile Asp Ala Ile Arg Ile Leu Gly Thr Asn Leu Ser
545 550 555 560
Tyr Asp Glu Leu Lys Ala Leu Ala Asp Thr Phe Ser Leu Asp Glu Asn
565 570 575
Gly Asn Lys Leu Lys Lys Gly Lys His Gly Met Arg Asn Phe Ile Ile
580 585 590
Asn Asn Val Ile Ser Asn Lys Arg Phe His Tyr Leu Ile Arg Tyr Gly
595 600 605
Asp Pro Ala His Leu His Glu Ile Ala Lys Asn Glu Ala Val Val Lys
610 615 620
Phe Val Leu Gly Arg Ile Ala Asp Ile Gln Lys Lys Gln Gly Gln Asn
625 630 635 640
Gly Lys Asn Gln Ile Asp Arg Tyr Tyr Glu Thr Cys Ile Gly Lys Asp
645 650 655
Lys Gly Lys Ser Val Ser Glu Lys Val Asp Ala Leu Thr Lys Ile Ile
660 665 670
Thr Gly Met Asn Tyr Asp Gln Phe Asp Lys Lys Arg Ser Val Ile Glu
675 680 685
Asp Thr Gly Arg Glu Asn Ala Glu Arg Glu Lys Phe Lys Lys Ile Ile
690 695 700
Ser Leu Tyr Leu Thr Val Ile Tyr His Ile Leu Lys Asn Ile Val Asn
705 710 715 720
Ile Asn Ala Arg Tyr Val Ile Gly Phe His Cys Val Glu Arg Asp Ala
725 730 735
Gln Leu Tyr Lys Glu Lys Gly Tyr Asp Ile Asn Leu Lys Lys Leu Glu
740 745 750
Glu Lys Gly Phe Ser Ser Val Thr Lys Leu Cys Ala Gly Ile Asp Glu
755 760 765
Thr Ala Pro Asp Lys Arg Lys Asp Val Glu Lys Glu Met Ala Glu Arg
770 775 780
Ala Lys Glu Ser Ile Asp Ser Leu Glu Ser Ala Asn Pro Lys Leu Tyr
785 790 795 800
Ala Asn Tyr Ile Lys Tyr Ser Asp Glu Lys Lys Ala Glu Glu Phe Thr
805 810 815
Arg Gln Ile Asn Arg Glu Lys Ala Lys Thr Ala Leu Asn Ala Tyr Leu
820 825 830
Arg Asn Thr Lys Trp Asn Val Ile Ile Arg Glu Asp Leu Leu Arg Ile
835 840 845
Asp Asn Lys Thr Cys Thr Leu Phe Ala Asn Lys Ala Val Ala Leu Glu
850 855 860
Val Ala Arg Tyr Val His Ala Tyr Ile Asn Asp Ile Ala Glu Val Asn
865 870 875 880
Ser Tyr Phe Gln Leu Tyr His Tyr Ile Met Gln Arg Ile Ile Met Asn
885 890 895
Glu Arg Tyr Glu Lys Ser Ser Gly Lys Val Ser Glu Tyr Phe Asp Ala
900 905 910
Val Asn Asp Glu Lys Lys Tyr Asn Asp Arg Leu Leu Lys Leu Leu Cys
915 920 925
Val Pro Phe Gly Tyr Cys Ile Pro Arg Phe Lys Asn Leu Ser Ile Glu
930 935 940
Ala Leu Phe Asp Arg Asn Glu Ala Ala Lys Phe Asp Lys Glu Lys Lys
945 950 955 960
Lys Val Ser Gly Asn Ser
965
<210> 46
<211> 1034
<212> PRT
<213> 未知的
<220>
<223> Cas13d（重叠群e-k87 11092736）
<400> 46
Met Lys Arg Gln Lys Thr Phe Ala Lys Arg Ile Gly Ile Lys Ser Thr
1 5 10 15
Val Ala Tyr Gly Gln Gly Lys Tyr Ala Ile Thr Thr Phe Gly Lys Gly
20 25 30
Ser Lys Ala Glu Ile Ala Val Arg Ser Ala Asp Pro Pro Glu Glu Thr
35 40 45
Leu Pro Thr Glu Ser Asp Ala Thr Leu Ser Ile His Ala Lys Phe Ala
50 55 60
Lys Ala Gly Arg Asp Gly Arg Glu Phe Lys Cys Gly Asp Val Asp Glu
65 70 75 80
Thr Arg Ile His Thr Ser Arg Ser Glu Tyr Glu Ser Leu Ile Ser Asn
85 90 95
Pro Ala Glu Ser Pro Arg Glu Asp Tyr Leu Gly Leu Lys Gly Thr Leu
100 105 110
Glu Arg Lys Phe Phe Gly Asp Glu Tyr Pro Lys Asp Asn Leu Arg Ile
115 120 125
Gln Ile Ile Tyr Ser Ile Leu Asp Ile Gln Lys Ile Leu Gly Leu Tyr
130 135 140
Val Glu Asp Ile Leu His Phe Val Asp Gly Leu Gln Asp Glu Pro Glu
145 150 155 160
Asp Leu Val Gly Leu Gly Leu Gly Asp Glu Lys Met Gln Lys Leu Leu
165 170 175
Ser Lys Ala Leu Pro Tyr Met Gly Phe Phe Gly Ser Thr Asp Val Phe
180 185 190
Lys Val Thr Lys Lys Arg Glu Glu Arg Ala Ala Ala Asp Glu His Asn
195 200 205
Ala Lys Val Phe Arg Ala Leu Gly Ala Ile Arg Gln Lys Leu Ala His
210 215 220
Phe Lys Trp Lys Glu Ser Leu Ala Ile Phe Gly Ala Asn Ala Asn Met
225 230 235 240
Pro Ile Arg Phe Phe Gln Gly Ala Thr Gly Gly Arg Gln Leu Trp Asn
245 250 255
Asp Val Ile Ala Pro Leu Trp Lys Lys Arg Ile Glu Arg Val Arg Lys
260 265 270
Ser Phe Leu Ser Asn Ser Ala Lys Asn Leu Trp Val Leu Tyr Gln Val
275 280 285
Phe Lys Asp Asp Thr Asp Glu Lys Lys Lys Ala Arg Ala Arg Gln Tyr
290 295 300
Tyr His Phe Ser Val Leu Lys Glu Gly Lys Asn Leu Gly Phe Asn Leu
305 310 315 320
Thr Lys Thr Arg Glu Tyr Phe Leu Asp Lys Phe Phe Pro Ile Phe His
325 330 335
Ser Ser Ala Pro Asp Val Lys Arg Lys Val Asp Thr Phe Arg Ser Lys
340 345 350
Phe Tyr Ala Ile Leu Asp Phe Ile Ile Tyr Glu Ala Ser Val Ser Val
355 360 365
Ala Asn Ser Gly Gln Met Gly Lys Val Ala Pro Trp Lys Gly Ala Ile
370 375 380
Asp Asn Ala Leu Val Lys Leu Arg Glu Ala Pro Asp Glu Glu Ala Lys
385 390 395 400
Glu Lys Ile Tyr Asn Val Leu Ala Ala Ser Ile Arg Asn Asp Ser Leu
405 410 415
Phe Leu Arg Leu Lys Ser Ala Cys Asp Lys Phe Gly Ala Glu Gln Asn
420 425 430
Arg Pro Val Phe Pro Asn Glu Leu Arg Asn Asn Arg Asp Ile Arg Asn
435 440 445
Val Arg Ser Glu Trp Leu Glu Ala Thr Gln Asp Val Asp Ala Ala Ala
450 455 460
Phe Val Gln Leu Ile Ala Phe Leu Cys Asn Phe Leu Glu Gly Lys Glu
465 470 475 480
Ile Asn Glu Leu Val Thr Ala Leu Ile Lys Lys Phe Glu Gly Ile Gln
485 490 495
Ala Leu Ile Asp Leu Leu Arg Asn Leu Glu Gly Val Asp Ser Ile Arg
500 505 510
Phe Glu Asn Glu Phe Ala Leu Phe Asn Asp Asp Lys Gly Asn Met Ala
515 520 525
Gly Arg Ile Ala Arg Gln Leu Arg Leu Leu Ala Ser Val Gly Lys Met
530 535 540
Lys Pro Asp Met Thr Asp Ala Lys Arg Val Leu Tyr Lys Ser Ala Leu
545 550 555 560
Glu Ile Leu Gly Ala Pro Pro Asp Glu Val Ser Asp Glu Trp Leu Ala
565 570 575
Glu Asn Ile Leu Leu Asp Lys Ser Asn Asn Asp Tyr Gln Lys Ala Lys
580 585 590
Lys Thr Val Asn Pro Phe Arg Asn Tyr Ile Ala Lys Asn Val Ile Thr
595 600 605
Ser Arg Ser Phe Tyr Tyr Leu Val Arg Tyr Ala Lys Pro Thr Ala Val
610 615 620
Arg Lys Leu Met Ser Asn Pro Lys Ile Val Arg Tyr Val Leu Lys Arg
625 630 635 640
Leu Pro Glu Lys Gln Val Ala Ser Tyr Tyr Ser Ala Ile Trp Thr Gln
645 650 655
Ser Glu Ser Asn Ser Asn Glu Met Val Lys Leu Ile Glu Met Ile Asp
660 665 670
Arg Leu Thr Thr Glu Ile Ala Gly Phe Ser Phe Ala Val Leu Lys Asp
675 680 685
Lys Lys Asp Ser Ile Val Ser Ala Ser Arg Glu Ser Arg Ala Val Asn
690 695 700
Leu Glu Val Glu Arg Leu Lys Lys Leu Thr Thr Leu Tyr Met Ser Ile
705 710 715 720
Ala Tyr Ile Ala Val Lys Ser Leu Val Lys Val Asn Ala Arg Tyr Phe
725 730 735
Ile Ala Tyr Ser Ala Leu Glu Arg Asp Leu Tyr Phe Phe Asn Glu Lys
740 745 750
Tyr Gly Glu Glu Phe Arg Leu His Phe Ile Pro Tyr Glu Leu Asn Gly
755 760 765
Lys Thr Cys Gln Phe Glu Tyr Leu Ala Ile Leu Lys Tyr Tyr Leu Ala
770 775 780
Arg Asp Glu Glu Thr Leu Lys Arg Lys Cys Glu Ile Cys Glu Glu Ile
785 790 795 800
Lys Val Gly Cys Glu Lys His Lys Lys Asn Ala Asn Pro Pro Tyr Glu
805 810 815
Tyr Asp Gln Glu Trp Ile Asp Lys Lys Lys Ala Leu Asn Ser Glu Arg
820 825 830
Lys Ala Cys Glu Arg Arg Leu His Phe Ser Thr His Trp Ala Gln Tyr
835 840 845
Ala Thr Lys Arg Asp Glu Asn Met Ala Lys His Pro Gln Lys Trp Tyr
850 855 860
Asp Ile Leu Ala Ser His Tyr Asp Glu Leu Leu Ala Leu Gln Ala Thr
865 870 875 880
Gly Trp Leu Ala Thr Gln Ala Arg Asn Asp Ala Glu His Leu Asn Pro
885 890 895
Val Asn Glu Phe Asp Val Tyr Ile Glu Asp Leu Arg Arg Tyr Pro Glu
900 905 910
Gly Thr Pro Lys Asn Lys Asp Tyr His Ile Gly Ser Tyr Phe Glu Ile
915 920 925
Tyr His Tyr Ile Arg Gln Arg Ala Tyr Leu Glu Glu Val Leu Ala Lys
930 935 940
Arg Lys Glu Tyr Arg Asp Ser Gly Ser Phe Thr Asp Glu Gln Leu Asp
945 950 955 960
Lys Leu Gln Lys Ile Leu Asp Asp Ile Arg Ala Arg Gly Ser Tyr Asp
965 970 975
Lys Asn Leu Leu Lys Leu Glu Tyr Leu Pro Phe Ala Tyr Asn Leu Pro
980 985 990
Arg Tyr Lys Asn Leu Thr Thr Glu Ala Leu Phe Asp Asp Asp Ser Val
995 1000 1005
Ser Gly Lys Lys Arg Val Ala Glu Trp Arg Glu Arg Glu Lys Thr
1010 1015 1020
Arg Glu Ala Glu Arg Glu Gln Arg Arg Gln Arg
1025 1030
<210> 47
<211> 30
<212> DNA
<213> 未知的
<220>
<223> 重叠群e-k87 11092736
<400> 47
gtgagaagtc tccttatggg gagatgctac 30
<210> 48
<211> 1022
<212> PRT
<213> 未知的
<220>
<223> Cas13d（160582958 基因49834）
<400> 48
Met Lys Asn Ser Val Thr Phe Lys Leu Ile Gln Ala Gln Glu Asn Lys
1 5 10 15
Glu Ala Ala Arg Lys Lys Ala Lys Asp Ile Ala Glu Gln Ala Arg Ile
20 25 30
Ala Lys Arg Asn Gly Val Val Lys Lys Glu Glu Asn Arg Ile Asn Arg
35 40 45
Ile Gln Ile Glu Ile Gln Thr Gln Lys Lys Ser Asn Thr Gln Asn Ala
50 55 60
Tyr His Leu Lys Ser Leu Ala Lys Ala Ala Gly Val Lys Ser Val Phe
65 70 75 80
Ala Ile Gly Asn Asp Leu Leu Met Thr Gly Phe Gly Pro Gly Asn Asp
85 90 95
Ala Thr Ile Glu Lys Arg Val Phe Gln Asn Arg Ala Ile Glu Thr Leu
100 105 110
Ser Ser Pro Glu Gln Tyr Ser Ala Glu Phe Gln Asn Lys Gln Phe Lys
115 120 125
Ile Lys Gly Asn Ile Lys Val Leu Asn His Ser Thr Gln Lys Met Glu
130 135 140
Glu Ile Gln Thr Glu Leu Gln Asp Asn Tyr Asn Arg Pro His Phe Asp
145 150 155 160
Leu Leu Gly Cys Lys Asn Val Leu Glu Gln Lys Tyr Phe Gly Arg Thr
165 170 175
Phe Ser Asp Asn Ile His Val Gln Ile Ala Tyr Asn Ile Met Asp Ile
180 185 190
Glu Lys Leu Leu Thr Pro Tyr Ile Asn Asn Ile Ile Tyr Thr Leu Asn
195 200 205
Glu Leu Met Arg Asp Asn Ser Lys Asp Asp Phe Phe Gly Cys Asp Ser
210 215 220
His Phe Ser Val Ala Tyr Leu Tyr Asp Glu Leu Lys Ala Gly Tyr Ser
225 230 235 240
Asp Arg Leu Lys Thr Lys Pro Asn Leu Ser Lys Asn Ile Asp Arg Ile
245 250 255
Trp Asn Asn Phe Cys Asn Tyr Met Asn Ser Asp Ser Gly Asn Thr Glu
260 265 270
Ala Arg Leu Ala Tyr Phe Gly Glu Leu Phe Tyr Lys Pro Lys Glu Thr
275 280 285
Gly Asp Ala Lys Ser Asp Tyr Lys Thr His Leu Ser Asn Asn Gln Lys
290 295 300
Glu Glu Trp Glu Leu Lys Ser Asp Lys Glu Val Tyr Asn Ile Phe Ala
305 310 315 320
Ile Leu Cys Asp Leu Arg His Phe Cys Thr His Gly Glu Ser Ile Thr
325 330 335
Pro Ser Gly Lys Pro Phe Pro Tyr Asn Leu Glu Lys Asn Leu Phe Pro
340 345 350
Glu Ala Lys Gln Val Leu Asn Ser Leu Phe Glu Glu Lys Ala Glu Ser
355 360 365
Leu Gly Ala Glu Ala Phe Gly Lys Thr Ala Gly Lys Thr Asp Val Ser
370 375 380
Ile Leu Leu Lys Val Phe Glu Lys Glu Gln Ala Ser Gln Lys Glu Gln
385 390 395 400
Gln Ala Leu Leu Lys Glu Tyr Tyr Asp Phe Lys Val Gln Lys Thr Tyr
405 410 415
Lys Asn Met Gly Phe Ser Ile Lys Lys Leu Arg Glu Ala Ile Met Glu
420 425 430
Ile Pro Asp Ala Ala Lys Phe Lys Asp Asp Leu Tyr Ser Ser Leu Arg
435 440 445
His Lys Leu Tyr Gly Leu Phe Asp Phe Ile Leu Val Lys His Phe Leu
450 455 460
Asp Thr Ser Asp Ser Glu Asn Leu Gln Asn Asn Asp Ile Phe Arg Gln
465 470 475 480
Leu Arg Ala Cys Arg Cys Glu Glu Glu Lys Asp Gln Val Tyr Arg Ser
485 490 495
Ile Ala Val Lys Val Trp Glu Lys Val Lys Lys Lys Glu Leu Asn Met
500 505 510
Phe Lys Gln Val Val Val Ile Pro Ser Leu Ser Lys Asp Glu Leu Lys
515 520 525
Gln Met Glu Met Thr Lys Asn Thr Glu Leu Leu Ser Ser Ile Glu Thr
530 535 540
Ile Ser Thr Gln Ala Ser Leu Phe Ser Glu Met Ile Phe Met Met Thr
545 550 555 560
Tyr Leu Leu Asp Gly Lys Glu Ile Asn Leu Leu Cys Thr Ser Leu Ile
565 570 575
Glu Lys Phe Glu Asn Ile Ala Ser Phe Asn Glu Val Leu Lys Ser Pro
580 585 590
Gln Ile Gly Tyr Glu Thr Lys Tyr Thr Glu Gly Tyr Ala Phe Phe Lys
595 600 605
Asn Ala Asp Lys Thr Ala Lys Glu Leu Arg Gln Val Asn Asn Met Ala
610 615 620
Arg Met Thr Lys Pro Leu Gly Gly Val Asn Thr Lys Cys Val Met Tyr
625 630 635 640
Asn Glu Ala Ala Lys Ile Leu Gly Ala Lys Pro Met Ser Lys Ala Glu
645 650 655
Leu Glu Ser Val Phe Asn Leu Asp Asn His Asp Tyr Thr Tyr Ser Pro
660 665 670
Ser Gly Lys Lys Ile Pro Asn Lys Asn Phe Arg Asn Phe Ile Ile Asn
675 680 685
Asn Val Ile Thr Ser Arg Arg Phe Leu Tyr Leu Ile Arg Tyr Gly Asn
690 695 700
Pro Glu Lys Ile Arg Lys Ile Ala Ile Asn Pro Ser Ile Ile Ser Phe
705 710 715 720
Val Leu Lys Gln Ile Pro Asp Glu Gln Ile Lys Arg Tyr Tyr Pro Pro
725 730 735
Cys Ile Gly Lys Arg Thr Asp Asp Val Thr Leu Met Arg Asp Glu Leu
740 745 750
Gly Lys Met Leu Gln Ser Val Asn Phe Glu Gln Phe Ser Arg Val Asn
755 760 765
Asn Lys Gln Asn Ala Lys Gln Asn Pro Asn Gly Glu Lys Ala Arg Leu
770 775 780
Gln Ala Cys Val Arg Leu Tyr Leu Thr Val Pro Tyr Leu Phe Ile Lys
785 790 795 800
Asn Met Val Asn Ile Asn Ala Arg Tyr Val Leu Ala Phe His Cys Leu
805 810 815
Glu Arg Asp His Ala Leu Cys Phe Asn Ser Arg Lys Leu Asn Asp Asp
820 825 830
Ser Tyr Asn Glu Met Ala Asn Lys Phe Gln Met Val Arg Lys Ala Lys
835 840 845
Lys Glu Gln Tyr Glu Lys Glu Tyr Lys Cys Lys Lys Gln Glu Thr Gly
850 855 860
Thr Ala His Thr Lys Lys Ile Glu Lys Leu Asn Gln Gln Ile Ala Tyr
865 870 875 880
Ile Asp Lys Asp Ile Lys Asn Met His Ser Tyr Thr Cys Arg Asn Tyr
885 890 895
Arg Asn Leu Val Ala His Leu Asn Val Val Ser Lys Leu Gln Asn Tyr
900 905 910
Val Ser Glu Leu Pro Asn Asp Tyr Gln Ile Thr Ser Tyr Phe Ser Phe
915 920 925
Tyr His Tyr Cys Met Gln Leu Gly Leu Met Glu Lys Val Ser Ser Lys
930 935 940
Asn Ile Pro Leu Val Glu Ser Leu Lys Asn Glu Ala Asn Asp Ala Gln
945 950 955 960
Ser Tyr Ser Ala Lys Lys Thr Leu Glu Tyr Phe Asp Leu Ile Glu Lys
965 970 975
Asn Arg Thr Tyr Cys Lys Asp Phe Leu Lys Ala Leu Asn Ala Pro Phe
980 985 990
Ser Tyr Asn Leu Pro Arg Phe Lys Asn Leu Ser Ile Glu Ala Leu Phe
995 1000 1005
Asp Lys Asn Ile Val Tyr Glu Gln Ala Asp Leu Lys Lys Glu
1010 1015 1020
<210> 49
<211> 36
<212> DNA
<213> 未知的
<220>
<223> Cas13d（160582958 基因49834）
<400> 49
gaactacacc cctctgttct tgtaggggtc taacac 36
<210> 50
<211> 877
<212> PRT
<213> 未知的
<220>
<223> Cas13d（重叠群tpg DJXD01000002.1）
<400> 50
Met Lys Lys Gln Lys Ser Lys Lys Thr Val Ser Lys Thr Ser Gly Leu
1 5 10 15
Lys Glu Ala Leu Ser Val Gln Gly Thr Val Ile Met Thr Ser Phe Gly
20 25 30
Lys Gly Asn Met Ala Asn Leu Ser Tyr Lys Ile Pro Ser Ser Gln Lys
35 40 45
Pro Gln Asn Leu Asn Ser Ser Ala Gly Leu Lys Asn Val Glu Val Ser
50 55 60
Gly Lys Lys Ile Lys Phe Gln Gly Arg His Pro Lys Ile Ala Thr Thr
65 70 75 80
Asp Asn Pro Leu Phe Lys Pro Gln Pro Gly Met Asp Leu Leu Cys Leu
85 90 95
Lys Asp Lys Leu Glu Met His Tyr Phe Gly Lys Thr Phe Asp Asp Asn
100 105 110
Ile His Ile Gln Leu Ile Tyr Gln Ile Leu Asp Ile Glu Lys Ile Leu
115 120 125
Ala Val His Val Asn Asn Ile Val Phe Thr Leu Asp Asn Val Leu His
130 135 140
Pro Gln Lys Glu Glu Leu Thr Glu Asp Phe Ile Gly Ala Gly Gly Trp
145 150 155 160
Arg Ile Asn Leu Asp Tyr Gln Thr Leu Arg Gly Gln Thr Asn Lys Tyr
165 170 175
Asp Arg Phe Lys Asn Tyr Ile Lys Arg Lys Glu Leu Leu Tyr Phe Gly
180 185 190
Glu Ala Phe Tyr His Glu Asn Glu Arg Arg Tyr Glu Glu Asp Ile Phe
195 200 205
Ala Ile Leu Thr Leu Leu Ser Ala Leu Arg Gln Phe Cys Phe His Ser
210 215 220
Asp Leu Ser Ser Asp Glu Ser Asp His Val Asn Ser Phe Trp Leu Tyr
225 230 235 240
Gln Leu Glu Asp Gln Leu Ser Asp Glu Phe Lys Glu Thr Leu Ser Ile
245 250 255
Leu Trp Glu Glu Val Thr Glu Arg Ile Asp Ser Glu Phe Leu Lys Thr
260 265 270
Asn Thr Val Asn Leu His Ile Leu Cys His Val Phe Pro Lys Glu Ser
275 280 285
Lys Glu Thr Ile Val Arg Ala Tyr Tyr Glu Phe Leu Ile Lys Lys Ser
290 295 300
Phe Lys Asn Met Gly Phe Ser Ile Lys Lys Leu Arg Glu Ile Met Leu
305 310 315 320
Glu Gln Ser Asp Leu Lys Ser Phe Lys Glu Asp Lys Tyr Asn Ser Val
325 330 335
Arg Ala Lys Leu Tyr Lys Leu Phe Asp Phe Ile Ile Thr Tyr Tyr Tyr
340 345 350
Asp His His Ala Phe Glu Lys Glu Ala Leu Val Ser Ser Leu Arg Ser
355 360 365
Ser Leu Thr Glu Glu Asn Lys Glu Glu Ile Tyr Ile Lys Thr Ala Arg
370 375 380
Thr Leu Ala Ser Ala Leu Gly Ala Asp Phe Lys Lys Ala Ala Ala Asp
385 390 395 400
Val Asn Ala Lys Asn Ile Arg Asp Tyr Gln Lys Lys Ala Asn Asp Tyr
405 410 415
Arg Ile Ser Phe Glu Asp Ile Lys Ile Gly Asn Thr Gly Ile Gly Tyr
420 425 430
Phe Ser Glu Leu Ile Tyr Met Leu Thr Leu Leu Leu Asp Gly Lys Glu
435 440 445
Ile Asn Asp Leu Leu Thr Thr Leu Ile Asn Lys Phe Asp Asn Ile Ile
450 455 460
Ser Phe Ile Asp Ile Leu Lys Lys Leu Asn Leu Glu Phe Lys Phe Lys
465 470 475 480
Pro Glu Tyr Ala Asp Phe Phe Asn Met Thr Asn Cys Arg Tyr Thr Leu
485 490 495
Glu Glu Leu Arg Val Ile Asn Ser Ile Ala Arg Met Gln Lys Pro Ser
500 505 510
Ala Asp Ala Arg Lys Ile Met Tyr Arg Asp Ala Leu Arg Ile Leu Gly
515 520 525
Met Asp Asn Arg Pro Asp Glu Glu Ile Asp Arg Glu Leu Glu Arg Thr
530 535 540
Met Pro Val Gly Ala Asp Gly Lys Phe Ile Lys Gly Lys Gln Gly Phe
545 550 555 560
Arg Asn Phe Ile Ala Ser Asn Val Ile Glu Ser Ser Arg Phe His Tyr
565 570 575
Leu Val Arg Tyr Asn Asn Pro His Lys Thr Arg Thr Leu Val Lys Asn
580 585 590
Pro Asn Val Val Lys Phe Val Leu Glu Gly Ile Pro Glu Thr Gln Ile
595 600 605
Lys Arg Tyr Phe Asp Val Cys Lys Gly Gln Glu Ile Pro Pro Thr Ser
610 615 620
Asp Lys Ser Ala Gln Ile Asp Val Leu Ala Arg Ile Ile Ser Ser Val
625 630 635 640
Asp Tyr Lys Ile Phe Glu Asp Val Pro Gln Ser Ala Lys Ile Asn Lys
645 650 655
Asp Asp Pro Ser Arg Asn Phe Ser Asp Ala Leu Lys Lys Gln Arg Tyr
660 665 670
Gln Ala Ile Val Ser Leu Tyr Leu Thr Val Met Tyr Leu Ile Thr Lys
675 680 685
Asn Leu Val Tyr Val Asn Ser Arg Tyr Val Ile Ala Phe His Cys Leu
690 695 700
Glu Arg Asp Ala Phe Leu His Gly Val Thr Leu Pro Lys Met Asn Lys
705 710 715 720
Lys Ile Val Tyr Ser Gln Leu Thr Thr His Leu Leu Thr Asp Lys Asn
725 730 735
Tyr Thr Thr Tyr Gly His Leu Lys Asn Gln Lys Gly His Arg Lys Trp
740 745 750
Tyr Val Leu Val Lys Asn Asn Leu Gln Asn Ser Asp Ile Thr Ala Val
755 760 765
Ser Ser Phe Arg Asn Ile Val Ala His Ile Ser Val Val Arg Asn Ser
770 775 780
Asn Glu Tyr Ile Ser Gly Ile Gly Glu Leu His Ser Tyr Phe Glu Leu
785 790 795 800
Tyr His Tyr Leu Val Gln Ser Met Ile Ala Lys Asn Asn Trp Tyr Asp
805 810 815
Thr Ser His Gln Pro Lys Thr Ala Glu Tyr Leu Asn Asn Leu Lys Lys
820 825 830
His His Thr Tyr Cys Lys Asp Phe Val Lys Ala Tyr Cys Ile Pro Phe
835 840 845
Gly Tyr Val Val Pro Arg Tyr Lys Asn Leu Thr Ile Asn Glu Leu Phe
850 855 860
Asp Arg Asn Asn Pro Asn Pro Glu Pro Lys Glu Glu Val
865 870 875
<210> 51
<211> 36
<212> PRT
<213> 智人（Homo Sapiens）
<400> 51
Cys Ala Ala Cys Thr Ala Cys Ala Ala Cys Cys Cys Cys Gly Thr Ala
1 5 10 15
Ala Ala Ala Ala Thr Ala Cys Gly Gly Gly Gly Thr Thr Cys Thr Gly
20 25 30
Ala Ala Ala Cys
35
<210> 52
<400> 52
000
<210> 53
<400> 53
000
<210> 54
<211> 124
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群6049000251
<400> 54
Leu Tyr Leu Thr Ser Phe Gly Lys Gly Asn Ala Ala Val Ile Glu Gln
1 5 10 15
Lys Ile Glu Pro Glu Asn Gly Tyr Arg Val Thr Gly Met Gln Ile Thr
20 25 30
Pro Ser Ile Thr Val Asn Lys Ala Thr Asp Glu Ser Val Arg Phe Arg
35 40 45
Val Lys Arg Lys Ile Ala Gln Lys Asp Glu Phe Ile Ala Asp Asn Pro
50 55 60
Met His Glu Gly Arg His Arg Ile Glu Pro Ser Ala Gly Ser Asp Met
65 70 75 80
Leu Gly Leu Lys Thr Lys Leu Glu Lys Tyr Tyr Phe Gly Lys Glu Phe
85 90 95
Asp Asp Asn Leu His Ile Gln Ile Ile Tyr Asn Ile Leu Asp Ile Glu
100 105 110
Lys Ile Leu Ala Val Tyr Ser Thr Asn Ile Thr Ala
115 120
<210> 55
<400> 55
000
<210> 56
<400> 56
000
<210> 57
<211> 358
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群546000275
<400> 57
Met Asp Ser Tyr Arg Pro Lys Leu Tyr Lys Leu Ile Asp Phe Cys Ile
1 5 10 15
Phe Lys His Tyr His Glu Tyr Thr Glu Ile Ser Glu Lys Asn Val Asp
20 25 30
Thr Leu Arg Ala Ala Val Ser Glu Glu Gln Lys Glu Ser Phe Tyr Ala
35 40 45
Asp Glu Ala Lys Arg Leu Trp Gly Ile Phe Asp Lys Gln Phe Leu Gly
50 55 60
Phe Cys Lys Lys Ile Asn Val Trp Val Asn Gly Ser His Glu Lys Glu
65 70 75 80
Ile Leu Gly Tyr Ile Asp Lys Asp Ala Tyr Arg Lys Lys Ser Asp Val
85 90 95
Ser Tyr Phe Ser Lys Phe Leu Tyr Ala Met Ser Phe Phe Leu Asp Gly
100 105 110
Lys Glu Ile Asn Asp Leu Leu Thr Thr Leu Ile Asn Lys Phe Asp Asn
115 120 125
Ile Ala Ser Phe Ile Ser Thr Ala Lys Glu Leu Asp Ala Glu Ile Asp
130 135 140
Arg Ile Leu Glu Lys Lys Leu Asp Pro Val Thr Gly Lys Pro Leu Lys
145 150 155 160
Gly Lys Asn Ser Phe Arg Asn Phe Ile Ala Asn Asn Val Ile Glu Asn
165 170 175
Lys Arg Phe Ile Tyr Val Ile Lys Phe Cys Asn Pro Lys Asn Val Leu
180 185 190
Lys Leu Val Lys Asn Thr Lys Val Thr Glu Phe Val Leu Lys Arg Met
195 200 205
Pro Glu Ser Gln Ile Asp Arg Tyr Tyr Ser Ser Cys Ile Asp Thr Glu
210 215 220
Lys Asn Pro Ser Val Asp Lys Lys Ile Ser Asp Leu Ala Glu Met Ile
225 230 235 240
Lys Lys Ile Ala Phe Asp Asp Phe Arg Asn Val Arg Gln Lys Thr Arg
245 250 255
Thr Arg Glu Glu Ser Leu Glu Lys Glu Arg Phe Lys Ala Val Ile Gly
260 265 270
Leu Tyr Leu Thr Val Val Tyr Leu Leu Ile Lys Asn Leu Val Asn Val
275 280 285
Asn Ser Arg Tyr Val Met Ala Phe His Cys Leu Glu Arg Asp Ala Lys
290 295 300
Leu Tyr Gly Ile Asn Ile Gly Lys Asn Tyr Ile Glu Leu Thr Glu Asp
305 310 315 320
Leu Cys Arg Glu Asn Glu Asn Ser Arg Ser Ala Tyr Leu Ala Arg Asn
325 330 335
Lys Arg Leu Arg Asp Cys Val Lys Gln Asn Ile Asp Asn Ala Lys Asn
340 345 350
Met Lys Ser Lys Glu Lys
355
<210> 58
<400> 58
000
<210> 59
<400> 59
000
<210> 60
<400> 60
000
<210> 61
<211> 149
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群4114000374
<400> 61
Asp Thr Lys Ile Asn Pro Gln Thr Trp Leu Tyr Gln Leu Glu Asn Thr
1 5 10 15
Pro Asp Leu Asp Asn Glu Tyr Arg Asp Thr Leu Asp His Phe Phe Asp
20 25 30
Glu Arg Phe Asn Glu Ile Asn Glu His Phe Val Thr Gln Asn Ala Thr
35 40 45
Asn Leu Cys Ile Met Lys Glu Val Phe Pro Asp Glu Asp Phe Lys Ser
50 55 60
Ile Ala Asp Leu Tyr Tyr Asp Phe Ile Val Val Lys Ser Tyr Lys Asn
65 70 75 80
Ile Gly Phe Ser Ile Lys Lys Leu Arg Glu Lys Met Leu Glu Leu Pro
85 90 95
Glu Ala Lys Arg Val Thr Ser Thr Glu Met Asp Ser Val Arg Ser Lys
100 105 110
Leu Tyr Lys Leu Ile Asp Phe Cys Ile Phe Lys His Tyr His Glu Lys
115 120 125
Pro Glu Thr Val Glu Met Ile Val Ser Met Leu Arg Ala Tyr Thr Ser
130 135 140
Glu Asp Met Lys Glu
145
<210> 62
<400> 62
000
<210> 63
<400> 63
000
<210> 64
<211> 372
<212> PRT
<213> 智人（Homo Sapiens）
<400> 64
Met Glu Ser Gly Gln Pro Ala Arg Arg Ile Ala Met Ala Pro Leu Leu
1 5 10 15
Glu Tyr Glu Arg Gln Leu Val Leu Glu Leu Leu Asp Thr Asp Gly Leu
20 25 30
Val Val Cys Ala Arg Gly Leu Gly Ala Asp Arg Leu Leu Tyr His Phe
35 40 45
Leu Gln Leu His Cys His Pro Ala Cys Leu Val Leu Val Leu Asn Thr
50 55 60
Gln Pro Ala Glu Glu Glu Tyr Phe Ile Asn Gln Leu Lys Ile Glu Gly
65 70 75 80
Val Glu His Leu Pro Arg Arg Val Thr Asn Glu Ile Thr Ser Asn Ser
85 90 95
Arg Tyr Glu Val Tyr Thr Gln Gly Gly Val Ile Phe Ala Thr Ser Arg
100 105 110
Ile Leu Val Val Asp Phe Leu Thr Asp Arg Ile Pro Ser Asp Leu Ile
115 120 125
Thr Gly Ile Leu Val Tyr Arg Ala His Arg Ile Ile Glu Ser Cys Gln
130 135 140
Glu Ala Phe Ile Leu Arg Leu Phe Arg Gln Lys Asn Lys Arg Gly Phe
145 150 155 160
Ile Lys Ala Phe Thr Asp Asn Ala Val Ala Phe Asp Thr Gly Phe Cys
165 170 175
His Val Glu Arg Val Met Arg Asn Leu Phe Val Arg Lys Leu Tyr Leu
180 185 190
Trp Pro Arg Phe His Val Ala Val Asn Ser Phe Leu Glu Gln His Lys
195 200 205
Pro Glu Val Val Glu Ile His Val Ser Met Thr Pro Thr Met Leu Ala
210 215 220
Ile Gln Thr Ala Ile Leu Asp Ile Leu Asn Ala Cys Leu Lys Glu Leu
225 230 235 240
Lys Cys His Asn Pro Ser Leu Glu Val Glu Asp Leu Ser Leu Glu Asn
245 250 255
Ala Ile Gly Lys Pro Phe Asp Lys Thr Ile Arg His Tyr Leu Asp Pro
260 265 270
Leu Trp His Gln Leu Gly Ala Lys Thr Lys Ser Leu Val Gln Asp Leu
275 280 285
Lys Ile Leu Arg Thr Leu Leu Gln Tyr Leu Ser Gln Tyr Asp Cys Val
290 295 300
Thr Phe Leu Asn Leu Leu Glu Ser Leu Arg Ala Thr Glu Lys Ala Phe
305 310 315 320
Gly Gln Asn Ser Gly Trp Leu Phe Leu Asp Ser Ser Thr Ser Met Phe
325 330 335
Ile Asn Ala Arg Ala Arg Val Tyr His Leu Pro Asp Ala Lys Met Ser
340 345 350
Lys Lys Glu Lys Ile Ser Glu Lys Met Glu Ile Lys Glu Gly Glu Gly
355 360 365
Ile Leu Trp Gly
370
<210> 65
<400> 65
000
<210> 66
<400> 66
000
<210> 67
<211> 320
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群721000619
<400> 67
Lys Glu Gly Ser Thr Met Ala Lys Asn Glu Lys Lys Lys Ser Thr Ala
1 5 10 15
Lys Ala Leu Gly Leu Lys Ser Ser Phe Val Val Asn Asn Asp Ile Tyr
20 25 30
Met Thr Ser Phe Gly Lys Gly Asn Lys Ala Val Leu Glu Lys Lys Ile
35 40 45
Thr Glu Asn Thr Ile Glu Asn Lys Ser Asp Thr Thr Tyr Phe Asp Val
50 55 60
Ile Asn Arg Asp Pro Lys Gly Phe Thr Leu Glu Gly Arg Arg Ile Ala
65 70 75 80
Asp Met Thr Ala Phe Ser Asn Asp Pro Lys Tyr His Val Asn Val Val
85 90 95
Asn Gly Lys Phe Leu Glu Asp Gln Leu Gly Ala Arg Ser Glu Leu Glu
100 105 110
Lys Lys Val Phe Gly Arg Thr Phe Asp Asp Asn Val His Ile Gln Leu
115 120 125
Ile His Asn Ile Leu Asp Ile Glu Lys Ile Met Ala Gln Tyr Val Ser
130 135 140
Asp Ile Val Tyr Leu Leu His Asn Thr Ile Lys Arg Asp Met Asn Asp
145 150 155 160
Asp Ile Met Gly Tyr Ile Ser Ile Arg Asn Ser Phe Asp Asp Phe Cys
165 170 175
His Pro Glu Arg Ile Pro Asp Arg Lys Ala Lys Asp Asn Leu Gln Lys
180 185 190
Gln His Asp Ile Phe Phe Asp Glu Ile Leu Lys Cys Gly Arg Leu Ala
195 200 205
Tyr Phe Gly Asn Ala Phe Phe Glu Asp Gly Ser Asp Asn Lys Glu Ile
210 215 220
Ala Lys Leu Lys Arg Tyr Lys Glu Ile Tyr His Ile Ile Ala Leu Met
225 230 235 240
Gly Ser Leu Arg Gln Ser Tyr Phe His Gly Glu Asn Ser Asp Lys Asn
245 250 255
Phe Gln Gly Pro Thr Trp Ala Tyr Thr Leu Glu Ser Asn Leu Thr Gly
260 265 270
Lys Tyr Lys Glu Phe Lys Asp Thr Leu Asp Lys Thr Phe Asp Glu Arg
275 280 285
Tyr Glu Met Ile Ser Lys Asp Phe Gly Ser Thr Asn Met Val Asn Leu
290 295 300
Gln Ile Leu Glu Glu Leu Leu Lys Met Leu Tyr Gly Asn Val Ser Pro
305 310 315 320
<210> 68
<400> 68
000
<210> 69
<211> 204
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群2002000411
<400> 69
Glu Lys Gln Asn Lys Ala Lys Tyr Gln Ala Ile Ile Ser Leu Tyr Leu
1 5 10 15
Met Val Met Tyr Gln Ile Val Lys Asn Met Ile Tyr Val Asn Ser Arg
20 25 30
Tyr Val Ile Ala Phe His Cys Leu Glu Arg Asp Ser Asn Gln Leu Leu
35 40 45
Gly Arg Phe Asn Ser Arg Asp Ala Ser Met Tyr Asn Lys Leu Thr Gln
50 55 60
Lys Phe Ile Thr Asp Lys Tyr Leu Asn Asp Gly Ala Gln Gly Cys Ser
65 70 75 80
Lys Lys Val Gly Asn Tyr Leu Ser His Asn Ile Thr Cys Cys Ser Asp
85 90 95
Glu Leu Arg Lys Glu Tyr Arg Asn Gln Val Asp His Phe Ala Val Val
100 105 110
Arg Met Ile Gly Lys Tyr Ala Ala Asp Ile Gly Lys Phe Ser Thr Trp
115 120 125
Phe Glu Leu Tyr His Tyr Val Met Gln Arg Ile Ile Phe Asp Lys Arg
130 135 140
Asn Pro Leu Ser Glu Thr Glu Arg Thr Tyr Lys Gln Leu Ile Ala Lys
145 150 155 160
His His Thr Tyr Cys Lys Asp Leu Val Lys Ala Leu Asn Thr Pro Phe
165 170 175
Gly Tyr Asn Leu Ala Arg Tyr Lys Asn Leu Ser Ile Gly Glu Leu Phe
180 185 190
Asp Arg Asn Asn Tyr Asn Ala Lys Thr Lys Glu Thr
195 200
<210> 70
<400> 70
000
<210> 71
<211> 449
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群13552000311
<400> 71
Leu Ile Asp Phe Leu Ile Tyr Asp Leu Tyr Tyr Asn Arg Lys Pro Ala
1 5 10 15
Arg Ile Glu Glu Ile Val Asp Lys Leu Arg Glu Ser Val Asn Asp Glu
20 25 30
Glu Lys Glu Ser Ile Tyr Ser Ala Glu Thr Lys Tyr Val Tyr Glu Ala
35 40 45
Leu Gly Lys Val Leu Val Arg Ser Leu Lys Lys Tyr Leu Asn Gly Ala
50 55 60
Thr Ile Arg Asp Leu Lys Asn Arg Tyr Asp Ala Lys Thr Ala Asn Arg
65 70 75 80
Ile Trp Asp Ile Ser Glu His Ser Lys Ser Gly His Val Asn Cys Phe
85 90 95
Cys Lys Leu Ile Tyr Met Met Thr Leu Met Leu Asp Gly Lys Glu Ile
100 105 110
Asn Asp Leu Leu Thr Thr Leu Val Asn Lys Phe Asp Asn Ile Ala Ser
115 120 125
Phe Ile Asp Val Met Asp Glu Leu Gly Leu Glu His Ser Phe Thr Asp
130 135 140
Asn Tyr Lys Met Phe Ala Asp Ser Lys Ala Ile Cys Leu Asp Leu Gln
145 150 155 160
Phe Ile Asn Ser Phe Ala Arg Met Ser Lys Ile Asp Asp Glu Lys Ser
165 170 175
Lys Arg Gln Leu Phe Arg Asp Ala Leu Val Val Leu Asp Ile Gly Asp
180 185 190
Lys Asn Glu Asp Trp Ile Glu Lys Tyr Leu Thr Ser Asp Ile Phe Lys
195 200 205
Arg Asp Glu Asn Gly Asn Lys Ile Asp Gly Glu Lys Arg Asp Phe Arg
210 215 220
Asn Phe Ile Ala Asn Asn Val Ile Lys Ser Ala Arg Phe Lys Tyr Leu
225 230 235 240
Val Lys Tyr Ser Ser Ala Asp Gly Met Ile Lys Leu Lys Lys Asn Glu
245 250 255
Lys Leu Ile Ser Phe Val Leu Glu Gln Leu Pro Glu Thr Gln Ile Asp
260 265 270
Arg Tyr Tyr Glu Ser Cys Gly Leu Asp Cys Ala Val Ala Asp Arg Lys
275 280 285
Val Arg Ile Glu Lys Leu Thr Gly Leu Ile Arg Asp Met Arg Phe Asp
290 295 300
Asn Phe Arg Gly Val Asn Tyr Ser Asn Asp Ala Cys Lys Lys Asp Lys
305 310 315 320
Gln Ala Lys Ala Lys Tyr Gln Ala Ile Ile Ser Leu Tyr Leu Met Val
325 330 335
Leu Tyr Gln Ile Val Lys Asn Met Ile Tyr Val Asn Ser Arg Tyr Val
340 345 350
Ile Ala Phe His Cys Leu Glu Arg Asp Leu Leu Phe Phe Asn Ile Glu
355 360 365
Leu Asp Asn Ser Tyr Gln Tyr Ser Asn Cys Asn Glu Leu Thr Glu Lys
370 375 380
Phe Ile Lys Asp Lys Tyr Met Lys Glu Gly Ala Leu Gly Phe Asn Met
385 390 395 400
Lys Ala Gly Arg Tyr Leu Thr Lys Asn Ile Gly Asn Cys Ser Asn Glu
405 410 415
Leu Arg Lys Ile Tyr Arg Asn Gln Val Asp His Phe Ala Val Val Arg
420 425 430
Lys Ile Gly Asn Tyr Ala Ala Asp Ile Ala Ser Val Gly Ser Trp Phe
435 440 445
Glu
<210> 72
<211> 96
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群10037000527
<400> 72
Tyr Met Asp Gln Asn Phe Ala Asn Ser Asp Ala Trp Ala Ile His Val
1 5 10 15
Tyr Arg Asn Lys Ile Gln His Leu Asp Ala Val Arg His Ala Asp Met
20 25 30
Tyr Ile Gly Asp Ile Arg Glu Phe His Ser Trp Phe Glu Leu Tyr His
35 40 45
Tyr Ile Ile Gln Arg Arg Ile Ile Asp Gln Tyr Ala Tyr Glu Ser Thr
50 55 60
Pro Gly Ser Ser Arg Asp Gly Ser Ala Ile Ile Asp Glu Glu Arg Leu
65 70 75 80
Asn Pro Ala Thr Arg Arg Tyr Phe Arg Leu Ile Thr Thr Tyr Lys Thr
85 90 95
<210> 73
<211> 519
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群238000329
<400> 73
Arg Tyr Asp Lys Asp Arg Ser Lys Ile Tyr Thr Met Met Asp Phe Val
1 5 10 15
Ile Tyr Arg Tyr Tyr Ile Asp Asn Asn Asn Asp Ser Ile Asp Phe Ile
20 25 30
Asn Lys Leu Arg Ser Ser Ile Asp Glu Lys Ser Lys Glu Lys Leu Tyr
35 40 45
Asn Glu Glu Ala Asn Arg Leu Trp Asn Lys Leu Lys Glu Tyr Met Leu
50 55 60
Tyr Ile Lys Glu Phe Asn Gly Lys Leu Ala Ser Arg Thr Pro Asp Arg
65 70 75 80
Asp Gly Asn Ile Ser Glu Phe Val Glu Ser Leu Pro Lys Ile His Arg
85 90 95
Leu Leu Pro Arg Gly Gln Lys Ile Ser Asn Phe Ser Lys Leu Met Tyr
100 105 110
Leu Leu Thr Met Phe Leu Asp Gly Lys Glu Ile Asn Asp Leu Leu Thr
115 120 125
Thr Leu Ile Asn Lys Phe Glu Asn Ile Gln Gly Phe Leu Asp Ile Met
130 135 140
Pro Glu Ile Asn Val Asn Ala Lys Phe Glu Pro Glu Tyr Val Phe Phe
145 150 155 160
Asn Lys Ser His Glu Ile Ala Gly Glu Leu Lys Leu Ile Lys Gly Phe
165 170 175
Ala Gln Met Gly Glu Pro Ala Ala Thr Leu Lys Leu Glu Met Thr Ala
180 185 190
Asp Ala Ile Lys Ile Leu Gly Thr Glu Lys Glu Asp Ala Glu Leu Ile
195 200 205
Lys Leu Ala Glu Ser Leu Phe Lys Asp Glu Asn Gly Lys Leu Leu Gly
210 215 220
Asn Lys Gln His Gly Met Arg Asn Phe Ile Gly Asn Asn Val Ile Lys
225 230 235 240
Ser Lys Arg Phe His Tyr Leu Ile Arg Tyr Gly Asp Pro Ala His Leu
245 250 255
His Lys Ile Ala Thr Asn Lys Asn Val Val Arg Phe Val Leu Gly Arg
260 265 270
Ile Ala Asp Met Gln Lys Lys Gln Gly Gln Lys Gly Lys Asn Gln Ile
275 280 285
Asp Arg Tyr Tyr Glu Val Cys Val Gly Asn Lys Asp Ile Lys Lys Thr
290 295 300
Ile Glu Glu Lys Ile Asp Ala Leu Thr Asp Ile Ile Val Asn Met Asn
305 310 315 320
Tyr Asp Gln Phe Glu Lys Lys Lys Ala Val Ile Glu Asn Gln Asn Arg
325 330 335
Gly Lys Thr Phe Glu Glu Lys Asn Lys Tyr Lys Arg Asp Asn Ala Glu
340 345 350
Arg Glu Lys Phe Lys Lys Ile Ile Ser Leu Tyr Leu Thr Val Ile Tyr
355 360 365
His Ile Leu Lys Asn Ile Val Asn Val Asn Ser Arg Tyr Ile Leu Gly
370 375 380
Phe His Cys Leu Glu Arg Asp Lys Gln Leu Tyr Ile Glu Lys Tyr Asn
385 390 395 400
Lys Asp Lys Leu Asp Gly Phe Val Ala Leu Thr Lys Phe Cys Leu Gly
405 410 415
Asp Glu Glu Arg Tyr Glu Asp Leu Lys Ala Lys Ala Gln Ala Ser Ile
420 425 430
Gln Ala Leu Glu Thr Ala Asn Pro Lys Leu Tyr Ala Lys Tyr Met Asn
435 440 445
Tyr Ser Asp Glu Glu Lys Lys Glu Glu Phe Lys Lys Gln Leu Asn Arg
450 455 460
Glu Arg Val Lys Asn Ala Arg Asn Ala Tyr Leu Lys Asn Ile Lys Asn
465 470 475 480
Tyr Ile Met Ile Arg Leu Gln Leu Arg Asp Gln Thr Asp Ser Ser Gly
485 490 495
Tyr Leu Cys Gly Glu Phe Arg Asp Lys Val Ala His Leu Glu Val Ala
500 505 510
Arg His Ala His Glu Tyr Ile
515
<210> 74
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 74
ggggccgggg ccggggccgg 20
<210> 75
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 75
gggccggggc cggggccggg 20
<210> 76
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 76
ggccggggcc ggggccgggg 20
<210> 77
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 77
gccggggccg gggccggggc 20
<210> 78
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 78
ccggggccgg ggccggggcc 20
<210> 79
<211> 20
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 79
cggggccggg gccggggccg 20
<210> 80
<211> 3
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 80
cag 3
<210> 81
<211> 6
<212> RNA
<213> 人工序列
<220>
<223> 间隔序列
<400> 81
ggggcc 6
<210> 82
<211> 93
<212> RNA
<213> 人工序列
<220>
<223> 支架序列
<400> 82
guuuaagagc uaugcuggaa acagcauagc aaguuuaaau aaggcuaguc cguuaucaac 60
uugaaaaagu ggcaccgagu cggugcuuuu uuu 93
<210> 83
<211> 83
<212> RNA
<213> 人工序列
<220>
<223> 支架序列
<400> 83
guuuuagagc uagaaauagc aaguuaaaau aaggcuaguc cguuaucaac uugaaaaagu 60
ggcaccgagu cggugcuuuu uuu 83
<210> 84
<211> 181
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群2643000492
<400> 84
Asn Gly Glu Ile Val Ser Leu Ala Glu Lys Glu Ala Phe Ser Ala Lys
1 5 10 15
Ile Ala Asp Lys Asn Ile Gly Cys Lys Ile Glu Asn Lys Gln Phe Arg
20 25 30
His Pro Lys Gly Tyr Asp Val Ile Ala Asp Asn Pro Ile Tyr Lys Gly
35 40 45
Ser Pro Arg Gln Asp Met Leu Gly Leu Lys Glu Thr Leu Glu Lys Arg
50 55 60
Tyr Phe Ser Pro Ser Asp Ser Ile Asp Asn Val Arg Val Gln Val Ala
65 70 75 80
His Asn Ile Leu Asp Ile Glu Lys Ile Leu Ala Glu Tyr Ile Thr Asn
85 90 95
Ala Val Tyr Ser Phe Asp Asn Ile Ala Gly Phe Gly Lys Asp Ile Ile
100 105 110
Gly Asp Asp Phe Ser Pro Val Tyr Thr Tyr Asp Lys Phe Glu Lys Ser
115 120 125
Asp Arg Tyr Glu Tyr Phe Lys Asn Leu Leu Asn Asn Ser Arg Leu Gly
130 135 140
Tyr Tyr Gly Gln Ala Phe Phe Glu Cys Asp Asp Ser Lys Glu Asn Lys
145 150 155 160
Lys Lys Lys Asp Ala Ile Lys Cys Tyr Asn Ile Ile Ala Leu Leu Ser
165 170 175
Gly Leu Arg His Trp
180
<210> 85
<211> 440
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群874000057
<400> 85
Met Ser Lys Asn Lys Glu Ser Tyr Ala Lys Gly Met Gly Leu Lys Ser
1 5 10 15
Ala Leu Val Ser Gly Ser Lys Val Tyr Met Thr Ser Phe Glu Gly Gly
20 25 30
Asn Asp Ala Lys Leu Glu Lys Val Val Glu Asn Ser Glu Ile Val Ser
35 40 45
Leu Ala Glu Lys Glu Ser Phe Ser Ala Glu Ile Phe Lys Lys Asn Ile
50 55 60
Gly Cys Lys Ile Glu Asn Lys Lys Phe Lys His Pro Lys Arg Tyr Asp
65 70 75 80
Val Ile Ala Asp Asn Pro Leu Tyr Lys Gly Ser Val Arg Gln Asp Met
85 90 95
Leu Gly Leu Lys Glu Thr Leu Glu Lys Arg Tyr Phe Asn Ser Ala Asp
100 105 110
Gly Thr Asp Asn Val Cys Ile Gln Val Ile His Asn Ile Leu Asp Ile
115 120 125
Glu Lys Ile Leu Ala Glu Tyr Ile Thr Asn Ala Val Tyr Ser Phe Asp
130 135 140
Asn Ile Ala Gly Phe Gly Glu Asp Ile Ile Gly Met Gly Gly Phe Lys
145 150 155 160
Pro Ile Tyr Thr Tyr Lys Gln Phe Lys Glu Pro Asp Lys Tyr Asn Lys
165 170 175
Lys Phe Asp Asp Ile Leu Asn Asn Ser Arg Leu Gly Tyr Tyr Gly Lys
180 185 190
Ala Phe Phe Glu Lys Asn Asp Leu Lys His Asn Pro Asn Lys Lys Lys
195 200 205
Arg Asp Lys Asn Pro Tyr Ile Leu Lys Tyr Asp Asn Glu Cys Tyr Tyr
210 215 220
Ile Ile Ala Leu Leu Ser Gly Leu Arg His Trp Asn Ile His Ser His
225 230 235 240
Ala Lys Asp Asp Leu Val Ser Tyr Arg Trp Leu Tyr Asn Leu Asp Ser
245 250 255
Ile Leu Asn Arg Glu Tyr Ile Ser Thr Leu Asn Tyr Leu Tyr Asp Asp
260 265 270
Ile Ala Asp Glu Leu Thr Glu Ser Phe Ser Lys Asn Ser Ser Ala Asn
275 280 285
Val Asn Tyr Ile Ala Glu Thr Leu Asn Ile Asp Pro Ser Glu Phe Ala
290 295 300
Gln Gln Tyr Phe Arg Phe Ser Ile Met Lys Glu Gln Lys Asn Met Gly
305 310 315 320
Phe Asn Val Ser Lys Leu Arg Glu Ile Met Leu Asp Arg Lys Glu Leu
325 330 335
Ser Asp Ile Arg Asp Asn His Arg Val Phe Asp Ser Ile Arg Ser Lys
340 345 350
Leu Tyr Thr Met Met Asp Phe Val Ile Tyr Arg Tyr Tyr Ile Glu Glu
355 360 365
Ala Ala Lys Thr Glu Ala Glu Asn Arg Asn Leu Pro Glu Asn Glu Lys
370 375 380
Lys Ile Ser Glu Lys Asp Phe Phe Val Ile Asn Leu Arg Gly Ser Phe
385 390 395 400
Asp Glu Asn Gln Lys Glu Lys Leu Tyr Ile Glu Glu Ala Lys Arg Leu
405 410 415
Trp Glu Lys Leu Lys Asp Ile Met Leu Lys Ile Lys Glu Phe Arg Gly
420 425 430
Glu Lys Val Lys Glu Tyr Lys Lys
435 440
<210> 86
<211> 137
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群4781000489
<400> 86
Leu Asp Lys Gln Leu Asp Tyr Glu Tyr Ile Arg Thr Leu Asn Tyr Met
1 5 10 15
Phe Asn Asp Ile Ala Asp Glu Leu Thr Arg Thr Phe Ser Lys Asn Ser
20 25 30
Ala Ala Asn Val Asn Tyr Ile Ala Glu Thr Leu Asn Ile Asp Pro Asn
35 40 45
Lys Phe Ala Glu Gln Tyr Phe Arg Phe Ser Ile Met Lys Glu Gln Lys
50 55 60
Asn Leu Gly Phe Asn Leu Thr Lys Leu Arg Glu Ser Met Leu Asp Arg
65 70 75 80
Arg Glu Leu Ser Asp Ile Arg Asp Asn His Asn Val Phe Asp Ser Ile
85 90 95
Arg Pro Lys Leu Tyr Thr Met Met Asp Phe Val Ile Tyr Lys His Tyr
100 105 110
Ile Asp Glu Ala Lys Lys Thr Glu Ala Glu Asn Lys Ser Leu Pro Asp
115 120 125
Asp Arg Lys Asn Leu Ser Glu Lys Asp
130 135
<210> 87
<211> 87
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群12144000352
<400> 87
Arg Met Gly Glu Pro Val Ala Asn Thr Lys Arg Val Met Met Ile Asp
1 5 10 15
Ala Val Lys Ile Leu Gly Thr Asp Leu Ser Asp Asp Glu Leu Lys Glu
20 25 30
Met Ala Asp Ser Phe Phe Lys Asp Ser Asp Gly Asn Leu Leu Lys Lys
35 40 45
Gly Lys His Gly Met Arg Asn Phe Ile Thr Asn Asn Val Ile Lys Asn
50 55 60
Lys Arg Phe His Tyr Leu Ile Arg Tyr Gly Asp Pro Ala His Leu His
65 70 75 80
Glu Ile Ala Lys Asn Glu Ala
85
<210> 88
<211> 414
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群5590000448
<400> 88
Val His Asn Asn Glu Glu Lys Asp Leu Ile Lys Tyr Thr Trp Leu Tyr
1 5 10 15
Asn Leu Asp Lys Tyr Leu Asp Ala Glu Tyr Ile Thr Thr Leu Asn Tyr
20 25 30
Met Tyr Asn Asp Ile Gly Asp Glu Leu Thr Asp Ser Phe Ser Lys Asn
35 40 45
Ser Ala Ala Asn Ile Asn Tyr Ile Ala Glu Thr Leu Gly Ile Asp Pro
50 55 60
Lys Thr Phe Ala Glu Gln Tyr Phe Arg Phe Ser Ile Met Lys Glu Gln
65 70 75 80
Lys Asn Leu Gly Phe Asn Leu Thr Lys Leu Arg Glu Val Met Leu Asp
85 90 95
Arg Lys Asp Met Ser Glu Ile Arg Glu Asn His Asn Asp Phe Asp Ser
100 105 110
Ile Arg Ala Lys Val Tyr Thr Met Met Asp Phe Val Ile Tyr Arg Tyr
115 120 125
Tyr Ile Glu Glu Ala Ala Lys Val Asn Ala Ala Asn Lys Ser Leu Pro
130 135 140
Asp Asn Glu Lys Ser Leu Ser Glu Lys Asp Ile Phe Val Ile Ser Leu
145 150 155 160
Arg Gly Ser Phe Asn Glu Asp Gln Lys Asp Arg Leu Tyr Tyr Asp Glu
165 170 175
Ala Gln Arg Leu Trp Ser Lys Val Gly Lys Leu Met Leu Lys Ile Lys
180 185 190
Lys Phe Arg Gly Lys Asp Thr Arg Lys Tyr Lys Asn Met Gly Thr Pro
195 200 205
Arg Ile Arg Arg Leu Ile Pro Glu Gly Arg Asp Ile Ser Thr Phe Ser
210 215 220
Lys Leu Met Tyr Ala Leu Thr Met Phe Leu Asp Gly Lys Glu Ile Asn
225 230 235 240
Asp Leu Leu Thr Thr Leu Ile Asn Lys Phe Asp Asn Ile Gln Ser Phe
245 250 255
Leu Lys Val Met Pro Leu Ile Gly Val Asn Ala Lys Phe Ala Glu Glu
260 265 270
Tyr Ser Phe Phe Asn Asn Ser Glu Lys Ile Ala Asp Glu Leu Arg Leu
275 280 285
Ile Lys Ser Phe Ala Arg Met Gly Glu Pro Val Ala Asp Ala Arg Arg
290 295 300
Ala Met Tyr Ile Asp Ala Ile Arg Ile Leu Gly Thr Asp Leu Ser Asp
305 310 315 320
Asp Glu Leu Lys Ala Leu Ala Asp Ser Phe Ser Leu Asp Glu Asn Gly
325 330 335
Asn Lys Leu Gly Lys Gly Lys His Gly Met Arg Asn Phe Ile Ile Asn
340 345 350
Asn Val Ile Thr Asn Lys Arg Phe His Tyr Leu Ile Arg Tyr Gly Asn
355 360 365
Pro Val His Leu His Glu Ile Ala Lys Asn Glu Ala Val Val Lys Phe
370 375 380
Val Leu Gly Arg Ile Ala Asp Ile Gln Lys Lys Gln Gly Gln Asn Gly
385 390 395 400
Lys Asn Gln Ile Asp Arg Tyr Tyr Glu Thr Cys Ile Gly Lys
405 410
<210> 89
<211> 345
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群525000349
<400> 89
Met Ser Lys Lys Glu Asn Arg Lys Ser Tyr Val Lys Gly Leu Gly Leu
1 5 10 15
Lys Ser Thr Leu Val Ser Asp Ser Lys Val Tyr Leu Thr Thr Phe Ala
20 25 30
Asp Gly Ser Asn Ala Lys Leu Glu Lys Cys Val Glu Asn Asn Lys Ile
35 40 45
Ile Cys Ile Ser Asn Asp Lys Glu Ala Phe Ala Ala Ser Ile Ala Asn
50 55 60
Lys Asn Val Gly Tyr Lys Ile Lys Asn Asp Glu Lys Phe Arg His Pro
65 70 75 80
Lys Gly Tyr Asp Ile Ile Ser Asn Asn Pro Leu Leu His Asn Asn Ser
85 90 95
Val Gln Gln Asp Met Leu Gly Leu Lys Asn Val Leu Glu Lys Arg Tyr
100 105 110
Phe Gly Lys Ser Ser Gly Gly Asp Asn Asn Leu Cys Ile Gln Ile Ile
115 120 125
His Asn Ile Ile Asp Ile Glu Lys Ile Leu Ser Glu Tyr Ile Pro Asn
130 135 140
Val Val Tyr Ala Phe Asn Asn Ile Ala Gly Phe Lys Asp Glu His Asn
145 150 155 160
Asn Ile Ile Asp Ile Ile Gly Thr Gln Thr Tyr Asn Ser Ser Tyr Thr
165 170 175
Tyr Ala Asp Phe Ser Lys Asp Lys Ser Asp Lys Lys Tyr Ile Glu Phe
180 185 190
Gln Lys Leu Leu Lys Asn Lys Arg Leu Gly Tyr Trp Gly Lys Ala Phe
195 200 205
Phe Thr Gly Gln Gly Asn Asn Ala Lys Val Arg Gln Glu Asn Gln Cys
210 215 220
Phe His Ile Ile Ala Leu Leu Ile Ser Leu Arg Asn Trp Ala Thr His
225 230 235 240
Ser Asn Glu Leu Asp Lys His Thr Lys Arg Thr Trp Leu Tyr Lys Leu
245 250 255
Asp Asp Thr Asn Ile Leu Asn Ala Glu Tyr Val Lys Thr Leu Asn Tyr
260 265 270
Leu Tyr Asp Thr Ile Ala Asp Glu Leu Thr Lys Ser Phe Ser Lys Asn
275 280 285
Gly Ala Val Asn Val Asn Tyr Leu Ala Lys Lys Tyr Asn Ile Lys Asp
290 295 300
Asp Leu Pro Gly Phe Ser Glu Gln Tyr Phe Arg Phe Ser Ile Met Lys
305 310 315 320
Glu Gln Lys Asn Leu Gly Phe Asn Ile Ser Lys Leu Arg Glu Asn Met
325 330 335
Leu Asp Phe Lys Asp Met Ser Val Ile
340 345
<210> 90
<211> 206
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群7229000302
<400> 90
Lys Lys Ile Ser Ser Leu Thr Lys Phe Cys Leu Gly Glu Ser Asp Glu
1 5 10 15
Lys Lys Leu Lys Ala Leu Ala Lys Lys Ser Leu Glu Glu Leu Lys Thr
20 25 30
Thr Asn Ser Lys Leu Tyr Glu Asn Tyr Ile Lys Tyr Ser Asp Glu Arg
35 40 45
Lys Ala Glu Glu Ala Lys Arg Gln Ile Asn Arg Glu Arg Ala Lys Thr
50 55 60
Ala Met Asn Ala His Leu Arg Asn Thr Lys Trp Asn Asp Ile Met Tyr
65 70 75 80
Gly Gln Leu Lys Asp Leu Ala Asp Ser Lys Ser Arg Ile Cys Ser Glu
85 90 95
Phe Arg Asn Lys Ala Ala His Leu Glu Val Ala Arg Tyr Ala His Met
100 105 110
Tyr Ile Asn Asp Ile Ser Glu Val Lys Ser Tyr Phe Arg Leu Tyr His
115 120 125
Tyr Ile Met Gln Arg Arg Ile Ile Asp Val Ile Glu Asn Asn Pro Lys
130 135 140
Ala Lys Tyr Glu Gly Lys Val Lys Val Tyr Phe Glu Asp Val Lys Lys
145 150 155 160
Asn Lys Lys Tyr Asn Lys Asn Leu Leu Lys Leu Met Cys Val Pro Phe
165 170 175
Gly Tyr Cys Ile Pro Arg Phe Lys Asn Leu Ser Ile Glu Gln Met Phe
180 185 190
Asp Met Asn Glu Thr Asp Asn Ser Asp Lys Lys Lys Glu Lys
195 200 205
<210> 91
<211> 95
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群3227000343
<400> 91
Ile Gly Asp Ile Ser Glu Val Asn Ser Tyr Phe Gln Leu Tyr His Tyr
1 5 10 15
Ile Met Gln Arg Ile Leu Ile Asp Lys Ile Gly Ser Lys Thr Thr Gly
20 25 30
Lys Ala Lys Glu Tyr Phe Asp Ser Val Ile Val Asn Lys Lys Tyr Asp
35 40 45
Asp Arg Leu Leu Lys Leu Leu Cys Ser Pro Leu Gly Tyr Cys Leu Thr
50 55 60
Arg Tyr Lys Asp Leu Ser Ile Glu Ala Leu Phe Asp Met Asn Glu Ala
65 70 75 80
Ala Lys Tyr Asp Lys Leu Asn Lys Glu Arg Lys Asn Lys Lys Lys
85 90 95
<210> 92
<211> 115
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组重叠群7030000469
<400> 92
Ser Ile Arg Ser Lys Leu Tyr Thr Met Met Asp Phe Val Ile Tyr Arg
1 5 10 15
Tyr Tyr Ile Glu Glu Ser Ala Lys Ala Ala Ala Glu Asn Lys Pro Ser
20 25 30
Glu Ser Asp Ser Phe Val Ile Arg Leu Arg Gly Ser Phe Asn Glu Asn
35 40 45
Gln Lys Glu Glu Leu Tyr Ile Glu Glu Ala Glu Arg Leu Trp Lys Lys
50 55 60
Phe Gly Glu Ile Met Leu Lys Ile Lys Glu Phe Arg Gly Glu Lys Val
65 70 75 80
Lys Glu Tyr Lys Lys Glu Val Pro Arg Ile Glu Arg Ile Leu Pro His
85 90 95
Gly Lys Asp Ile Ser Ala Phe Ser Lys Leu Met Tyr Met Leu Ser Met
100 105 110
Phe Leu Asp
115
<210> 93
<211> 234
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d肠道宏基因组P17E0k2120140920, c87000043
<400> 93
Met Tyr Phe Ser Lys Met Ile Tyr Met Leu Thr Tyr Phe Leu Asp Gly
1 5 10 15
Lys Glu Ile Asn Asp Leu Leu Thr Thr Leu Ile Ser Lys Phe Asp Asn
20 25 30
Ile Lys Glu Phe Leu Lys Ile Met Lys Ser Ser Ala Val Asp Val Glu
35 40 45
Cys Glu Leu Thr Ala Gly Tyr Lys Leu Phe Asn Asp Ser Gln Arg Ile
50 55 60
Thr Asn Glu Leu Phe Ile Val Lys Asn Ile Ala Ser Met Arg Lys Pro
65 70 75 80
Ala Ala Ser Ala Lys Leu Thr Met Phe Arg Asp Ala Leu Thr Ile Leu
85 90 95
Gly Ile Asp Asp Lys Ile Thr Asp Asp Arg Ile Ser Glu Ile Leu Lys
100 105 110
Leu Lys Glu Lys Gly Lys Gly Ile His Gly Leu Arg Asn Phe Ile Thr
115 120 125
Asn Asn Val Ile Glu Ser Ser Arg Phe Val Tyr Leu Ile Lys Tyr Ala
130 135 140
Asn Ala Gln Lys Ile Arg Glu Val Ala Lys Asn Glu Lys Val Val Met
145 150 155 160
Phe Val Leu Gly Gly Ile Pro Asp Thr Gln Ile Glu Arg Tyr Tyr Lys
165 170 175
Ser Cys Val Glu Phe Pro Asp Met Asn Ser Ser Leu Glu Ala Lys Arg
180 185 190
Ser Glu Leu Ala Arg Met Ile Lys Asn Ile Ser Phe Asp Asp Phe Lys
195 200 205
Asn Val Lys Gln Gln Ala Lys Gly Arg Glu Asn Val Ala Lys Glu Arg
210 215 220
Ala Lys Ala Val Ile Gly Leu Tyr Leu Thr
225 230
<210> 94
<211> 939
<212> PRT
<213> 未知的
<220>
<223> 重叠群emb OBVH01003037.1, 人肠道宏基因组序列
<400> 94
Met Ala Lys Lys Lys Arg Ile Thr Ala Lys Glu Arg Lys Gln Asn His
1 5 10 15
Arg Glu Leu Leu Met Lys Lys Ala Asp Ser Asn Ala Glu Lys Glu Lys
20 25 30
Ala Lys Lys Pro Val Val Glu Asn Lys Pro Asp Thr Ala Ile Ser Lys
35 40 45
Asp Asn Thr Pro Lys Pro Asn Lys Glu Ile Lys Lys Ser Lys Ala Lys
50 55 60
Leu Ala Gly Val Lys Trp Val Ile Lys Ala Asn Asp Asp Val Ala Tyr
65 70 75 80
Ile Ser Ser Phe Gly Lys Gly Asn Asn Ser Val Leu Glu Lys Arg Ile
85 90 95
Met Gly Asp Val Ser Ser Asn Val Asn Lys Asp Ser His Met Tyr Val
100 105 110
Asn Pro Lys Tyr Thr Lys Lys Asn Tyr Glu Ile Lys Asn Gly Phe Ser
115 120 125
Ser Gly Ser Ser Leu Val Thr Tyr Pro Asn Lys Pro Asp Lys Asn Ser
130 135 140
Gly Met Asp Ala Leu Cys Leu Lys Pro Tyr Phe Glu Lys Asp Phe Phe
145 150 155 160
Gly His Ile Phe Thr Asp Asn Met His Ile Gln Ala Ile Tyr Asn Ile
165 170 175
Phe Asp Ile Glu Lys Ile Leu Ala Lys His Ile Thr Asn Ile Ile Tyr
180 185 190
Thr Val Asn Ser Phe Asp Arg Asn Tyr Asn Gln Ser Gly Asn Asp Thr
195 200 205
Ile Gly Phe Gly Leu Asn Tyr Arg Val Pro Tyr Ser Glu Tyr Gly Gly
210 215 220
Gly Lys Asp Ser Asn Gly Glu Pro Lys Asn Gln Ser Lys Trp Glu Lys
225 230 235 240
Arg Asp Asn Phe Ile Lys Phe Tyr Asn Glu Ser Lys Pro His Leu Gly
245 250 255
Tyr Tyr Glu Asn Ile Phe Tyr Asp His Gly Glu Pro Ile Ser Glu Glu
260 265 270
Lys Phe Tyr Asn Tyr Leu Asn Ile Leu Asn Phe Ile Arg Asn Asn Thr
275 280 285
Phe His Tyr Lys Asp Asp Asp Ile Glu Leu Tyr Ser Glu Asn Tyr Ser
290 295 300
Glu Glu Phe Val Phe Ile Asn Cys Leu Asn Lys Phe Val Lys Asn Lys
305 310 315 320
Phe Lys Asn Val Asn Lys Asn Phe Ile Ser Asn Glu Lys Asn Asn Leu
325 330 335
Tyr Ile Ile Leu Asn Ala Tyr Gly Lys Asp Thr Glu Asn Val Glu Val
340 345 350
Val Lys Lys Tyr Ser Lys Glu Leu Tyr Lys Leu Ser Val Leu Lys Thr
355 360 365
Asn Lys Asn Leu Gly Val Asn Val Lys Lys Leu Arg Glu Ser Ala Ile
370 375 380
Glu Tyr Gly Tyr Cys Pro Leu Pro Tyr Asp Lys Glu Lys Glu Val Ala
385 390 395 400
Lys Leu Ser Ser Val Lys His Lys Leu Tyr Lys Thr Tyr Asp Phe Val
405 410 415
Ile Thr His Tyr Leu Asn Ser Asn Asp Lys Leu Leu Leu Glu Ile Val
420 425 430
Glu Thr Leu Arg Leu Ser Lys Asn Asp Asp Glu Lys Glu Asn Val Tyr
435 440 445
Lys Lys Tyr Ala Glu Lys Leu Phe Lys Ala Asp Asp Val Ile Asn Pro
450 455 460
Ile Lys Ala Ile Ser Lys Leu Phe Ala Arg Lys Gly Asn Lys Leu Phe
465 470 475 480
Lys Glu Lys Ile Ile Ile Lys Lys Glu Tyr Ile Glu Asp Val Ser Ile
485 490 495
Asp Lys Asn Ile Tyr Asp Phe Thr Lys Val Ile Phe Phe Met Thr Cys
500 505 510
Phe Leu Asp Gly Lys Glu Ile Asn Asp Leu Leu Thr Asn Ile Ile Ser
515 520 525
Lys Leu Gln Val Ile Glu Asp His Asn Asn Val Ile Lys Phe Ile Ser
530 535 540
Asn Asn Lys Asp Ala Val Tyr Lys Asp Tyr Ser Asp Lys Tyr Ala Ile
545 550 555 560
Phe Arg Asn Ala Gly Lys Ile Ala Thr Glu Leu Glu Ala Ile Lys Ser
565 570 575
Ile Ala Arg Met Glu Asn Lys Ile Glu Asn Ala Pro Gln Glu Pro Leu
580 585 590
Leu Lys Asp Ala Leu Leu Ser Leu Gly Val Ser Asp Asp Thr Lys Val
595 600 605
Leu Glu Asn Thr Tyr Asn Lys Tyr Phe Asp Ser Lys Glu Lys Thr Asp
610 615 620
Lys Gln Ser Gln Lys Val Ser Thr Phe Leu Met Asn Asn Val Ile Asn
625 630 635 640
Asn Asn Arg Phe Lys Tyr Val Ile Lys Tyr Ile Asn Pro Ala Asp Ile
645 650 655
Asn Gly Leu Ala Lys Asn Arg Tyr Leu Val Lys Phe Val Leu Ser Lys
660 665 670
Ile Pro Glu Glu Gln Ile Asp Ser Tyr Tyr Lys Leu Phe Ser Asn Glu
675 680 685
Glu Glu Pro Gly Cys Glu Glu Lys Ile Lys Leu Leu Thr Lys Lys Ile
690 695 700
Ser Lys Leu Asn Phe Gln Thr Leu Phe Glu Asn Asn Lys Ile Pro Asn
705 710 715 720
Val Glu Lys Glu Lys Lys Lys Ala Ile Ile Thr Leu Tyr Phe Thr Ile
725 730 735
Val Tyr Ile Leu Val Lys Asn Leu Val Asn Ile Asn Gly Leu Tyr Thr
740 745 750
Leu Ala Leu Tyr Phe Val Glu Arg Asp Gly Tyr Phe Tyr Lys Asp Ile
755 760 765
Cys Gly Lys Lys Asp Lys Lys Lys Ser Tyr Asn Asp Val Asp Tyr Leu
770 775 780
Leu Leu Pro Glu Ile Phe Ser Gly Ser Lys Tyr Arg Glu Glu Thr Lys
785 790 795 800
Asn Leu Lys Leu Pro Lys Glu Lys Asp Arg Asp Ile Met Lys Lys Tyr
805 810 815
Leu Pro Asn Asp Lys Asp Arg Glu Lys Tyr Asn Lys Phe Phe Thr Ala
820 825 830
Tyr Arg Asn Asn Ile Val His Leu Asn Ile Ile Ala Lys Leu Ser Glu
835 840 845
Leu Thr Lys Asn Ile Asp Lys Asp Ile Asn Ser Tyr Phe Asp Ile Tyr
850 855 860
His Tyr Cys Thr Gln Arg Val Met Phe Asn Tyr Cys Lys Glu Lys Asn
865 870 875 880
Asp Val Val Leu Ala Lys Met Lys Asp Leu Ala His Ile Lys Ser Asp
885 890 895
Cys Asn Glu Phe Ser Ser Lys His Thr Tyr Pro Phe Ser Ser Ala Val
900 905 910
Leu Arg Phe Met Asn Leu Pro Phe Ala Tyr Asn Val Pro Arg Phe Lys
915 920 925
Asn Leu Ser Tyr Lys Lys Phe Phe Asp Lys Gln
930 935
<210> 95
<211> 877
<212> PRT
<213> 未知的
<220>
<223> 重叠群tpg DJXD01000002.1
<400> 95
Met Lys Lys Gln Lys Ser Lys Lys Thr Val Ser Lys Thr Ser Gly Leu
1 5 10 15
Lys Glu Ala Leu Ser Val Gln Gly Thr Val Ile Met Thr Ser Phe Gly
20 25 30
Lys Gly Asn Met Ala Asn Leu Ser Tyr Lys Ile Pro Ser Ser Gln Lys
35 40 45
Pro Gln Asn Leu Asn Ser Ser Ala Gly Leu Lys Asn Val Glu Val Ser
50 55 60
Gly Lys Lys Ile Lys Phe Gln Gly Arg His Pro Lys Ile Ala Thr Thr
65 70 75 80
Asp Asn Pro Leu Phe Lys Pro Gln Pro Gly Met Asp Leu Leu Cys Leu
85 90 95
Lys Asp Lys Leu Glu Met His Tyr Phe Gly Lys Thr Phe Asp Asp Asn
100 105 110
Ile His Ile Gln Leu Ile Tyr Gln Ile Leu Asp Ile Glu Lys Ile Leu
115 120 125
Ala Val His Val Asn Asn Ile Val Phe Thr Leu Asp Asn Val Leu His
130 135 140
Pro Gln Lys Glu Glu Leu Thr Glu Asp Phe Ile Gly Ala Gly Gly Trp
145 150 155 160
Arg Ile Asn Leu Asp Tyr Gln Thr Leu Arg Gly Gln Thr Asn Lys Tyr
165 170 175
Asp Arg Phe Lys Asn Tyr Ile Lys Arg Lys Glu Leu Leu Tyr Phe Gly
180 185 190
Glu Ala Phe Tyr His Glu Asn Glu Arg Arg Tyr Glu Glu Asp Ile Phe
195 200 205
Ala Ile Leu Thr Leu Leu Ser Ala Leu Arg Gln Phe Cys Phe His Ser
210 215 220
Asp Leu Ser Ser Asp Glu Ser Asp His Val Asn Ser Phe Trp Leu Tyr
225 230 235 240
Gln Leu Glu Asp Gln Leu Ser Asp Glu Phe Lys Glu Thr Leu Ser Ile
245 250 255
Leu Trp Glu Glu Val Thr Glu Arg Ile Asp Ser Glu Phe Leu Lys Thr
260 265 270
Asn Thr Val Asn Leu His Ile Leu Cys His Val Phe Pro Lys Glu Ser
275 280 285
Lys Glu Thr Ile Val Arg Ala Tyr Tyr Glu Phe Leu Ile Lys Lys Ser
290 295 300
Phe Lys Asn Met Gly Phe Ser Ile Lys Lys Leu Arg Glu Ile Met Leu
305 310 315 320
Glu Gln Ser Asp Leu Lys Ser Phe Lys Glu Asp Lys Tyr Asn Ser Val
325 330 335
Arg Ala Lys Leu Tyr Lys Leu Phe Asp Phe Ile Ile Thr Tyr Tyr Tyr
340 345 350
Asp His His Ala Phe Glu Lys Glu Ala Leu Val Ser Ser Leu Arg Ser
355 360 365
Ser Leu Thr Glu Glu Asn Lys Glu Glu Ile Tyr Ile Lys Thr Ala Arg
370 375 380
Thr Leu Ala Ser Ala Leu Gly Ala Asp Phe Lys Lys Ala Ala Ala Asp
385 390 395 400
Val Asn Ala Lys Asn Ile Arg Asp Tyr Gln Lys Lys Ala Asn Asp Tyr
405 410 415
Arg Ile Ser Phe Glu Asp Ile Lys Ile Gly Asn Thr Gly Ile Gly Tyr
420 425 430
Phe Ser Glu Leu Ile Tyr Met Leu Thr Leu Leu Leu Asp Gly Lys Glu
435 440 445
Ile Asn Asp Leu Leu Thr Thr Leu Ile Asn Lys Phe Asp Asn Ile Ile
450 455 460
Ser Phe Ile Asp Ile Leu Lys Lys Leu Asn Leu Glu Phe Lys Phe Lys
465 470 475 480
Pro Glu Tyr Ala Asp Phe Phe Asn Met Thr Asn Cys Arg Tyr Thr Leu
485 490 495
Glu Glu Leu Arg Val Ile Asn Ser Ile Ala Arg Met Gln Lys Pro Ser
500 505 510
Ala Asp Ala Arg Lys Ile Met Tyr Arg Asp Ala Leu Arg Ile Leu Gly
515 520 525
Met Asp Asn Arg Pro Asp Glu Glu Ile Asp Arg Glu Leu Glu Arg Thr
530 535 540
Met Pro Val Gly Ala Asp Gly Lys Phe Ile Lys Gly Lys Gln Gly Phe
545 550 555 560
Arg Asn Phe Ile Ala Ser Asn Val Ile Glu Ser Ser Arg Phe His Tyr
565 570 575
Leu Val Arg Tyr Asn Asn Pro His Lys Thr Arg Thr Leu Val Lys Asn
580 585 590
Pro Asn Val Val Lys Phe Val Leu Glu Gly Ile Pro Glu Thr Gln Ile
595 600 605
Lys Arg Tyr Phe Asp Val Cys Lys Gly Gln Glu Ile Pro Pro Thr Ser
610 615 620
Asp Lys Ser Ala Gln Ile Asp Val Leu Ala Arg Ile Ile Ser Ser Val
625 630 635 640
Asp Tyr Lys Ile Phe Glu Asp Val Pro Gln Ser Ala Lys Ile Asn Lys
645 650 655
Asp Asp Pro Ser Arg Asn Phe Ser Asp Ala Leu Lys Lys Gln Arg Tyr
660 665 670
Gln Ala Ile Val Ser Leu Tyr Leu Thr Val Met Tyr Leu Ile Thr Lys
675 680 685
Asn Leu Val Tyr Val Asn Ser Arg Tyr Val Ile Ala Phe His Cys Leu
690 695 700
Glu Arg Asp Ala Phe Leu His Gly Val Thr Leu Pro Lys Met Asn Lys
705 710 715 720
Lys Ile Val Tyr Ser Gln Leu Thr Thr His Leu Leu Thr Asp Lys Asn
725 730 735
Tyr Thr Thr Tyr Gly His Leu Lys Asn Gln Lys Gly His Arg Lys Trp
740 745 750
Tyr Val Leu Val Lys Asn Asn Leu Gln Asn Ser Asp Ile Thr Ala Val
755 760 765
Ser Ser Phe Arg Asn Ile Val Ala His Ile Ser Val Val Arg Asn Ser
770 775 780
Asn Glu Tyr Ile Ser Gly Ile Gly Glu Leu His Ser Tyr Phe Glu Leu
785 790 795 800
Tyr His Tyr Leu Val Gln Ser Met Ile Ala Lys Asn Asn Trp Tyr Asp
805 810 815
Thr Ser His Gln Pro Lys Thr Ala Glu Tyr Leu Asn Asn Leu Lys Lys
820 825 830
His His Thr Tyr Cys Lys Asp Phe Val Lys Ala Tyr Cys Ile Pro Phe
835 840 845
Gly Tyr Val Val Pro Arg Tyr Lys Asn Leu Thr Ile Asn Glu Leu Phe
850 855 860
Asp Arg Asn Asn Pro Asn Pro Glu Pro Lys Glu Glu Val
865 870 875
<210> 96
<211> 36
<212> DNA
<213> 未知的
<220>
<223> CasRX/Cas13d DR
<400> 96
caactacaac cccgtaaaaa tacggggttc tgaaac 36
<210> 97
<211> 984
<212> PRT
<213> 未知的
<220>
<223> 重叠群OGZC01000639.1
<400> 97
Met Lys Lys Lys Asn Ile Arg Ala Thr Arg Glu Ala Leu Lys Ala Gln
1 5 10 15
Lys Ile Lys Lys Ser Gln Glu Asn Glu Ala Leu Lys Lys Gln Lys Leu
20 25 30
Ala Glu Glu Ala Ala Gln Lys Arg Arg Glu Glu Leu Glu Lys Lys Asn
35 40 45
Leu Ala Gln Trp Glu Glu Thr Ser Ala Glu Gly Arg Arg Ser Arg Val
50 55 60
Lys Ala Val Gly Val Lys Ser Val Phe Val Val Gly Asp Asp Leu Tyr
65 70 75 80
Leu Ala Thr Phe Gly Asn Gly Asn Glu Thr Val Leu Glu Lys Lys Ile
85 90 95
Thr Pro Asp Gly Lys Ile Thr Thr Phe Pro Glu Glu Glu Thr Phe Thr
100 105 110
Ala Lys Leu Lys Phe Ala Gln Thr Glu Pro Thr Val Ala Thr Ser Ile
115 120 125
Gly Ile Ser Asn Gly Arg Ile Val Leu Pro Glu Ile Ser Val Asp Asn
130 135 140
Pro Leu His Thr Thr Met Gln Lys Asn Thr Ile Lys Arg Ser Ala Gly
145 150 155 160
Glu Asp Ile Leu Gln Leu Lys Asp Val Leu Glu Asn Arg Tyr Phe Asp
165 170 175
Arg Ser Phe Asn Asp Asp Leu His Ile Arg Leu Ile Tyr Asn Ile Leu
180 185 190
Asp Ile Glu Lys Ile Leu Ala Glu Tyr Thr Thr Asn Ala Val Phe Ala
195 200 205
Ile Asp Asn Val Ser Gly Cys Ser Asp Asp Phe Leu Ser Asn Phe Ser
210 215 220
Thr Arg Asn Gln Trp Asp Glu Phe Gln Asn Pro Glu Gln His Arg Glu
225 230 235 240
His Phe Gly Asn Lys Asp Asn Val Ile Cys Ser Val Lys Lys Gln Gln
245 250 255
Asp Leu Phe Phe Asn Phe Phe Lys Asn Asn Arg Ile Gly Tyr Phe Gly
260 265 270
Lys Ala Phe Phe His Ala Glu Ser Glu Arg Lys Ile Val Lys Lys Thr
275 280 285
Glu Lys Glu Val Tyr His Ile Leu Thr Leu Ile Gly Ser Leu Arg Gln
290 295 300
Trp Ile Thr His Ser Thr Glu Gly Gly Ile Ser Arg Leu Trp Leu Tyr
305 310 315 320
Gln Leu Glu Asp Ala Leu Ser Arg Glu Tyr Gln Glu Thr Met Asn Asn
325 330 335
Cys Tyr Asn Ser Thr Ile Tyr Gly Leu Gln Lys Asp Phe Glu Lys Thr
340 345 350
Asn Ala Pro Asn Leu Asn Phe Leu Ala Glu Ile Leu Gly Lys Asn Ala
355 360 365
Ser Glu Leu Ala Glu Pro Tyr Phe Arg Phe Ile Ile Thr Lys Glu Tyr
370 375 380
Lys Asn Leu Gly Phe Ser Ile Lys Thr Leu Arg Glu Met Leu Leu Asp
385 390 395 400
Gln Pro Asp Leu Gln Glu Ile Arg Glu Asn His Asn Val Tyr Asp Ser
405 410 415
Ile Arg Ser Lys Leu Tyr Lys Met Ile Asp Phe Val Leu Val Tyr Ala
420 425 430
Tyr Ser Asn Glu Arg Lys Ser Lys Ala Asp Ala Leu Ala Ser Asn Leu
435 440 445
Arg Ser Ala Ile Thr Glu Asp Ala Lys Lys Arg Ile Tyr Gln Asn Glu
450 455 460
Ala Asp Gln Leu Trp Thr Ser Tyr Gln Glu Leu Phe Lys Arg Ile Arg
465 470 475 480
Gly Phe Lys Gly Ala Gln Val Lys Glu Tyr Ser Ser Lys Asn Met Pro
485 490 495
Ile Pro Ile Gln Lys Gln Ile Gln Asn Ile Leu Lys Pro Ala Glu Gln
500 505 510
Val Thr Tyr Phe Thr Lys Leu Met Tyr Leu Leu Thr Met Phe Leu Asp
515 520 525
Gly Lys Glu Ile Asn Asp Leu Leu Thr Thr Leu Ile Asn Lys Phe Asp
530 535 540
Asn Ile Ser Ser Leu Leu Lys Thr Met Glu Gln Leu Glu Leu Gln Thr
545 550 555 560
Thr Phe Lys Glu Asp Tyr Thr Phe Phe Gln Gln Ser Ser Arg Leu Cys
565 570 575
Lys Glu Ile Thr Gln Leu Lys Ser Phe Ala Arg Met Gly Asn Pro Ile
580 585 590
Ser Asn Leu Lys Glu Val Met Met Val Asp Ala Ile Gln Ile Leu Gly
595 600 605
Thr Glu Lys Ser Glu Gln Glu Leu Gln Ser Met Ala Cys Phe Phe Phe
610 615 620
Arg Asp Lys Asn Gly Lys Lys Leu Asn Thr Gly Glu His Gly Met Arg
625 630 635 640
Asn Phe Ile Gly Asn Asn Val Ile Ser Asn Thr Arg Phe Gln Tyr Leu
645 650 655
Ile Arg Tyr Gly Asn Pro Gln Lys Leu His Thr Leu Ser Gln Asn Glu
660 665 670
Thr Val Val Arg Phe Val Leu Ser Arg Ile Ala Lys Asn Gln Arg Val
675 680 685
Gln Gly Met Asn Gly Lys Asn Gln Ile Asp Arg Tyr Tyr Glu Thr Cys
690 695 700
Gly Gly Thr Asn Ser Trp Ser Val Ser Glu Glu Glu Lys Ile Asn Phe
705 710 715 720
Leu Cys Lys Ile Leu Thr Asn Met Ser Tyr Asp Gln Phe Gln Asp Val
725 730 735
Lys Gln Ser Gly Ala Glu Ile Thr Ala Glu Glu Lys Arg Lys Lys Glu
740 745 750
Arg Tyr Lys Ala Ile Ile Ser Leu Tyr Leu Thr Val Leu Tyr Gln Leu
755 760 765
Ile Lys Asn Leu Val Asn Ile Asn Ala Arg Tyr Ile Ile Ala Phe His
770 775 780
Cys Leu Glu Arg Asp Ala Ile Leu Tyr Ser Ser Lys Phe Asn Thr Ser
785 790 795 800
Ile Asn Leu Lys Lys Arg Tyr Thr Ala Leu Thr Glu Met Ile Leu Gly
805 810 815
Tyr Glu Thr Asp Glu Lys Ala Arg Arg Lys Asp Thr Arg Thr Val Tyr
820 825 830
Glu Lys Ala Glu Ala Ala Lys Asn Arg His Leu Lys Asn Val Lys Trp
835 840 845
Asn Cys Lys Thr Arg Glu Asn Leu Glu Asn Ala Asp Lys Asn Ala Ile
850 855 860
Val Ala Phe Arg Asn Ile Val Ala His Leu Trp Ile Ile Arg Asp Ala
865 870 875 880
Asp Arg Phe Ile Thr Gly Met Gly Ala Met Lys Arg Tyr Phe Asp Cys
885 890 895
Tyr His Tyr Leu Leu Gln Arg Glu Leu Gly Tyr Ile Leu Glu Lys Ser
900 905 910
Asn Gln Gly Ser Glu Tyr Thr Lys Lys Ser Leu Glu Lys Val Gln Gln
915 920 925
Tyr His Ser Tyr Cys Lys Asp Phe Leu His Met Leu Cys Leu Pro Phe
930 935 940
Ala Tyr Cys Ile Pro Arg Tyr Lys Asn Leu Ser Ile Ala Glu Leu Phe
945 950 955 960
Asp Arg His Glu Pro Glu Ala Glu Pro Lys Glu Glu Ala Ser Ser Val
965 970 975
Asn Asn Ser Gln Phe Ile Thr Thr
980
<210> 98
<211> 978
<212> PRT
<213> 未知的
<220>
<223> 重叠群emb OHBM01000764.1
<220>
<221> 尚未归类的特征
<222> (1)..(222)
<223> Xaa可以是任何天然存在的氨基酸
<400> 98
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
1 5 10 15
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
65 70 75 80
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
130 135 140
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
145 150 155 160
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
165 170 175
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa His Pro
210 215 220
Leu Gln Lys Arg Tyr Arg Tyr Leu Thr Ser Thr Asn Leu Lys Ser Phe
225 230 235 240
Glu Thr Tyr Lys Asn Asn Leu Val Asn Lys Lys Lys Phe Asp Leu Asp
245 250 255
Arg Val Lys Lys Ile Pro Gln Leu Ala Tyr Phe Gly Ser Ala Phe Tyr
260 265 270
Asn Thr Pro Glu Asp Thr Ser Ala Lys Ile Thr Lys Thr Lys Ile Lys
275 280 285
Ser Asn Glu Glu Ile Tyr Tyr Thr Phe Met Leu Leu Ser Thr Ala Arg
290 295 300
Asn Phe Ser Ala His Tyr Leu Asp Arg Asn Arg Ala Lys Ser Ser Asp
305 310 315 320
Ala Glu Asp Phe Asp Gly Thr Ser Val Ile Met Tyr Asn Leu Asp Asn
325 330 335
Glu Glu Leu Tyr Lys Lys Leu Tyr Asn Lys Lys Val His Met Ala Leu
340 345 350
Thr Gly Met Lys Lys Val Leu Asp Ala Asn Phe Asn Lys Lys Val Glu
355 360 365
His Leu Asn Asn Ser Phe Ile Lys Asn Ser Ala Lys Asp Phe Val Ile
370 375 380
Leu Cys Glu Val Leu Gly Ile Lys Ser Arg Asp Glu Lys Thr Lys Phe
385 390 395 400
Val Lys Asp Tyr Tyr Asp Phe Val Val Arg Lys Asn Tyr Lys His Leu
405 410 415
Gly Phe Ser Val Lys Glu Leu Arg Glu Leu Leu Phe Ala Asn His Asp
420 425 430
Ser Asn Lys Tyr Ile Lys Glu Phe Asp Lys Ile Ser Asn Lys Lys Phe
435 440 445
Asp Ser Val Arg Ser Arg Leu Asn Arg Leu Ala Asp Tyr Ile Ile Tyr
450 455 460
Asp Tyr Tyr Asn Lys Asn Asn Ala Lys Val Ser Asp Leu Val Lys Tyr
465 470 475 480
Leu Arg Ala Ala Ala Asp Asp Glu Gln Lys Lys Lys Ile Tyr Leu Asn
485 490 495
Glu Ser Ile Asn Leu Val Lys Ser Gly Ile Leu Glu Arg Ile Lys Lys
500 505 510
Ile Leu Pro Lys Leu Asn Gly Lys Ile Ile Gly Asn Met Gln Pro Asp
515 520 525
Ser Thr Ile Thr Ala Ser Met Leu His Asn Thr Gly Lys Asp Trp His
530 535 540
Pro Ile Ser Glu Asn Ala His Tyr Phe Thr Lys Trp Ile Tyr Thr Leu
545 550 555 560
Thr Leu Phe Met Asp Gly Lys Glu Ile Asn Asp Leu Val Thr Thr Leu
565 570 575
Ile Asn Lys Phe Asp Asn Ile Ala Ser Phe Ile Glu Val Leu Lys Ser
580 585 590
Gln Ser Val Cys Thr His Phe Ser Glu Glu Arg Lys Met Phe Ile Asp
595 600 605
Ser Ala Glu Ile Cys Ser Glu Leu Ser Ala Met Asn Ser Phe Ala Arg
610 615 620
Met Glu Ala Pro Gly Ala Ser Ser Lys Arg Ala Met Phe Val Glu Ala
625 630 635 640
Ala Arg Ile Leu Gly Asp Asn Arg Ser Lys Glu Glu Leu Glu Glu Tyr
645 650 655
Phe Asp Thr Leu Phe Asp Lys Ser Ala Ser Lys Lys Glu Lys Gly Phe
660 665 670
Arg Asn Phe Ile Arg Asn Asn Val Val Asp Ser Asn Arg Phe Lys Tyr
675 680 685
Leu Thr Arg Tyr Thr Asp Thr Ser Ser Val Lys Ala Phe Ser Asn Asn
690 695 700
Lys Ala Leu Val Lys Phe Ala Ile Lys Asp Ile Pro Gln Glu Gln Ile
705 710 715 720
Leu Arg Tyr Tyr Asn Ser Cys Phe Gly Ala Ser Glu Arg Tyr Tyr Asn
725 730 735
Asp Gly Met Ser Asp Lys Leu Val Glu Ala Ile Gly Lys Ile Asn Leu
740 745 750
Met Gln Phe Asn Gly Val Ile Gln Gln Ala Asp Arg Asn Met Leu Pro
755 760 765
Glu Glu Lys Lys Lys Ala Asn Ala Gln Lys Glu Lys Tyr Lys Ser Ile
770 775 780
Ile Arg Leu Tyr Leu Thr Val Cys Tyr Leu Phe Phe Lys Asn Leu Val
785 790 795 800
Tyr Val Asn Ser Arg Tyr Tyr Ser Ala Phe Tyr Asn Leu Glu Lys Asp
805 810 815
Arg Ser Leu Phe Glu Ile Asn Gly Glu Leu Lys Pro Thr Gly Lys Phe
820 825 830
Asp Glu Gly His Tyr Thr Gly Leu Val Lys Leu Phe Ile Asp Asn Gly
835 840 845
Trp Ile Asn Pro Arg Ala Ser Ala Tyr Leu Thr Val Asn Leu Ala Asn
850 855 860
Ser Asp Glu Thr Ala Ile Arg Thr Phe Arg Asn Thr Ala Glu His Leu
865 870 875 880
Glu Ala Leu Arg Asn Ala Asp Lys Tyr Leu Asn Asp Leu Lys Gln Phe
885 890 895
Asp Ser Tyr Phe Glu Ile Tyr His Tyr Ile Thr Gln Arg Asn Ile Lys
900 905 910
Glu Lys Cys Glu Met Leu Lys Glu Gln Thr Val Lys Tyr Asn Asn Asp
915 920 925
Leu Leu Lys Tyr His Gly Tyr Ser Lys Asp Phe Val Lys Ala Leu Cys
930 935 940
Val Pro Phe Gly Tyr Asn Leu Pro Arg Phe Lys Asn Leu Ser Ile Asp
945 950 955 960
Ala Leu Phe Asp Lys Asn Asp Lys Arg Glu Lys Leu Lys Lys Gly Phe
965 970 975
Glu Asp
<210> 99
<211> 1023
<212> PRT
<213> 未知的
<220>
<223> 重叠群emb OHCP01000044.1
<400> 99
Met Ala Lys Lys Ile Thr Ala Lys Gln Lys Arg Glu Glu Lys Glu Arg
1 5 10 15
Leu Asn Lys Gln Lys Trp Ala Lys Asn Asp Ser Val Ile Ile Val Pro
20 25 30
Glu Thr Lys Glu Glu Ile Lys Thr Gly Glu Ile Gln Asp Asn Asn Arg
35 40 45
Lys Arg Ser Arg Gln Lys Ser Gln Ala Lys Ala Met Gly Leu Lys Ala
50 55 60
Val Leu Ser Phe Asp Asn Lys Ile Ala Ile Ala Ser Phe Val Ser Ser
65 70 75 80
Lys Asn Ala Lys Ser Ser His Ile Glu Arg Ile Thr Asp Lys Glu Gly
85 90 95
Thr Thr Ile Ser Val Asn Ser Lys Met Phe Glu Ser Ser Val Asn Lys
100 105 110
Arg Asp Ile Asn Ile Glu Lys Arg Ile Thr Ile Glu Glu Pro Gln Gln
115 120 125
Asp Gly Thr Ile Lys Lys Glu Glu Lys Gly Val Lys Ser Thr Thr Cys
130 135 140
Asn Pro Tyr Phe Lys Val Gly Gly Lys Asp Tyr Ile Gly Ile Lys Glu
145 150 155 160
Ile Ala Glu Glu His Phe Phe Gly Arg Ala Phe Pro Asn Glu Asn Leu
165 170 175
Arg Val Gln Ile Ala Tyr Asn Ile Phe Asp Val Gln Lys Ile Leu Gly
180 185 190
Thr Phe Val Asn Asn Ile Ile Tyr Ser Phe Tyr Asn Leu Ser Arg Asp
195 200 205
Glu Val Gln Ser Asp Asn Asp Val Ile Gly Met Leu Tyr Ser Ile Ser
210 215 220
Asp Tyr Asp Arg Gln Lys Glu Thr Glu Thr Phe Leu Gln Ala Lys Ser
225 230 235 240
Leu Leu Lys Gln Thr Glu Ala Tyr Tyr Ala Tyr Phe Asp Asp Val Phe
245 250 255
Lys Lys Asn Lys Lys Pro Asp Lys Asn Lys Glu Gly Asp Asn Ser Lys
260 265 270
Gln Tyr Gln Glu Asn Leu Arg His Asn Phe Asn Ile Leu Arg Val Leu
275 280 285
Ser Phe Leu Arg Gln Ile Cys Met His Ala Glu Val His Val Ser Asp
290 295 300
Asp Glu Gly Cys Thr Arg Thr Gln Asn Tyr Thr Asp Ser Leu Glu Ala
305 310 315 320
Leu Phe Asn Ile Ser Lys Ala Phe Gly Lys Lys Met Pro Glu Leu Lys
325 330 335
Thr Leu Ile Asp Asn Ile Tyr Ser Lys Gly Ile Asn Ala Ile Asn Asp
340 345 350
Glu Phe Val Lys Asn Gly Lys Asn Asn Leu Tyr Ile Leu Ser Lys Val
355 360 365
Tyr Pro Asn Glu Lys Arg Glu Val Leu Leu Arg Glu Tyr Tyr Asn Phe
370 375 380
Val Val Cys Lys Glu Gly Ser Asn Ile Gly Ile Ser Thr Arg Lys Leu
385 390 395 400
Lys Glu Thr Met Ile Ala Gln Asn Met Pro Ser Leu Lys Glu Glu Asn
405 410 415
Thr Tyr Arg Asn Lys Leu Tyr Thr Val Met Asn Phe Ile Leu Val Arg
420 425 430
Glu Leu Lys Asn Cys Ala Thr Ile Arg Glu Gln Met Ile Lys Glu Leu
435 440 445
Arg Ala Asn Met Asp Glu Glu Glu Gly Arg Asp Arg Ile Tyr Ser Lys
450 455 460
Tyr Ala Lys Glu Ile Tyr Leu Tyr Val Lys Asp Lys Leu Lys Leu Met
465 470 475 480
Leu Asn Val Phe Lys Glu Glu Ala Glu Gly Ile Ile Ile Pro Gly Lys
485 490 495
Glu Asp Pro Val Lys Phe Ser His Gly Lys Leu Asp Lys Lys Glu Ile
500 505 510
Glu Ser Phe Cys Leu Thr Thr Lys Asn Thr Glu Asp Ile Thr Lys Val
515 520 525
Ile Tyr Phe Leu Cys Lys Phe Leu Asp Gly Lys Glu Ile Asn Glu Leu
530 535 540
Cys Cys Ala Met Met Asn Lys Leu Asp Gly Ile Ser Asp Leu Ile Glu
545 550 555 560
Thr Ala Lys Gln Cys Gly Glu Asp Val Glu Phe Val Asp Gln Phe Lys
565 570 575
Cys Leu Ser Lys Cys Ala Thr Met Ser Asn Gln Ile Arg Ile Val Lys
580 585 590
Asn Ile Ser Arg Met Lys Lys Glu Met Thr Ile Asp Asn Asp Thr Ile
595 600 605
Phe Leu Asp Ala Leu Glu Leu Leu Gly Arg Lys Ile Glu Lys Tyr Gln
610 615 620
Lys Asp Lys Asn Gly Asp Tyr Val Lys Asp Glu Lys Gly Lys Lys Val
625 630 635 640
Tyr Thr Lys Asp Tyr Asn Asn Phe Gln Asp Met Phe Phe Glu Gly Lys
645 650 655
Asn His Arg Val Arg Asn Phe Val Ser Asn Asn Val Ile Lys Ser Lys
660 665 670
Trp Phe Ser Tyr Val Val Arg Tyr Asn Lys Pro Ala Glu Cys Gln Ala
675 680 685
Leu Met Arg Asn Ser Lys Leu Val Lys Phe Ala Leu Asp Glu Leu Pro
690 695 700
Asp Ser Gln Ile Glu Lys Tyr Tyr Ile Ser Val Phe Gly Glu Lys Ser
705 710 715 720
Ser Ser Ser Asn Glu Glu Met Arg Arg Glu Leu Leu Lys Lys Leu Cys
725 730 735
Asp Phe Ser Val Arg Gly Phe Leu Asp Glu Ile Val Leu Leu Ser Glu
740 745 750
Asp Glu Met Lys Gln Lys Asp Lys Phe Ser Glu Lys Glu Lys Lys Lys
755 760 765
Ser Leu Ile Arg Leu Tyr Leu Thr Ile Val Tyr Leu Ile Thr Lys Ser
770 775 780
Met Val Lys Ile Asn Thr Arg Phe Ser Ile Ala Cys Ala Thr Tyr Glu
785 790 795 800
Arg Asp Tyr Ile Leu Leu Cys Gln Ser Glu Lys Ala Glu Arg Ala Trp
805 810 815
Glu Lys Gly Ala Thr Ala Phe Ala Leu Thr Arg Lys Phe Leu Asn His
820 825 830
Asp Lys Pro Thr Phe Glu Gln Tyr Tyr Thr Arg Glu Arg Glu Ile Ser
835 840 845
Ala Met Pro Gln Glu Lys Arg Lys Glu Leu Arg Lys Glu Asn Asp Gln
850 855 860
Leu Leu Lys Lys Thr His Tyr Ser Lys His Ala Tyr Cys Tyr Ile Val
865 870 875 880
Asp Asn Val Asn Asn Leu Thr Gly Ala Val Ala Asn Asp Asn Gly Arg
885 890 895
Gly Leu Pro Cys Leu Ser Glu Lys Asn Asp Asn Ala Asn Leu Phe Leu
900 905 910
Glu Met Arg Asn Lys Ile Val His Leu Asn Val Val His Asp Met Val
915 920 925
Lys Tyr Ile Asn Glu Ile Lys Asn Ile Thr Ser Tyr Tyr Ala Phe Phe
930 935 940
Cys Tyr Val Leu Gln Arg Met Ile Ile Gly Asn Asn Ser Asn Glu Gln
945 950 955 960
Asn Lys Phe Lys Ala Lys Tyr Ser Lys Thr Leu Gln Glu Phe Gly Thr
965 970 975
Tyr Ser Lys Asp Leu Met Trp Val Leu Asn Leu Pro Phe Ala Tyr Asn
980 985 990
Leu Pro Arg Tyr Lys Asn Leu Ser Asn Glu Gln Leu Phe Tyr Asp Glu
995 1000 1005
Glu Glu Arg Met Glu Lys Ile Val Gly Arg Lys Asn Asp Ser Arg
1010 1015 1020
<210> 100
<211> 926
<212> PRT
<213> 未知的
<220>
<223> 重叠群emb OGDF01008514.1
<400> 100
Met Thr Glu Thr Lys Pro Lys Arg Glu Asp Ile Ala Lys Thr Pro Ala
1 5 10 15
Ala Lys Ser Arg Ser Lys Ala Ala Gly Leu Lys Ser Thr Phe Ala Val
20 25 30
Asn Gly Ser Val Leu Leu Thr Ser Phe Gly Arg Gly Asn Asp Ala Val
35 40 45
Pro Glu Lys Leu Ile Thr Glu Lys Ala Val Ser Glu Ile Asn Thr Val
50 55 60
Lys Pro Arg Phe Ser Val Glu Lys Pro Ala Thr Ser Tyr Ser Ser Ser
65 70 75 80
Phe Gly Ile Lys Ser His Ile Ser Ala Thr Ala Asp Asn Pro Leu Ala
85 90 95
Gly Arg Ala Pro Val Gly Glu Asp Ala Ile His Ala Lys Glu Val Leu
100 105 110
Glu Gln Arg Val Phe Gly Lys Thr Phe Ser Asp Asp Asn Ile His Ile
115 120 125
Gln Leu Ile Tyr Asn Ile Leu Asp Ile Arg Lys Ile Leu Ser Thr Tyr
130 135 140
Ala Asn Asn Val Val Phe Thr Ile Asn Ser Met Arg Arg Leu Asp Glu
145 150 155 160
Tyr Asp Arg Glu Gln Asp Tyr Leu Gly Tyr Leu Tyr Thr Gly Asn Ser
165 170 175
Tyr Glu Arg Leu Leu Asp Ile Ala Asp Lys Tyr Ala Val Asp Gly Glu
180 185 190
Asp Trp Arg Asn Thr Ala Ala Gly Ile Ser Asn Asp Phe Glu Lys Lys
195 200 205
Gln Phe Gln Thr Ile Asn Gly Phe Trp Asp Leu Leu Asp Met Ile Glu
210 215 220
Pro Tyr Met Cys Tyr Phe Ser Glu Ala Phe Phe Cys Glu Thr Thr Val
225 230 235 240
Lys Asp Pro Asp Ser Gly Arg Ile Val Pro Cys Leu Glu Gln Arg Ser
245 250 255
Asp Gly Asp Ile Tyr Asn Ile Leu Arg Ile Leu Ser Ile Val Arg Gln
260 265 270
Thr Cys Met His Asp Asn Ala Ser Met Arg Thr Val Met Phe Thr Leu
275 280 285
Gly Gln Asn Ser Val Arg Asp Arg Lys Asn Gly Phe Asp Glu Leu Ala
290 295 300
Glu Leu Leu Asp Tyr Leu Tyr Asp Glu Lys Ile Asp Ile Val Asn Arg
305 310 315 320
Asp Phe Leu Arg Asn Gln Lys Asn Asn Ile Glu Leu Leu Ser Arg Ile
325 330 335
Tyr Gly Ser Ser Ala Asp Ser Pro Glu Arg Asp Arg Leu Val Gln Asn
340 345 350
Phe Tyr Asp Phe Arg Val Leu Ser Gln Asp Lys Asn Leu Gly Phe Ser
355 360 365
Ile Lys Lys Leu Arg Glu Lys Leu Leu Asp Ser Pro Ala Leu Ser Val
370 375 380
Val Arg Ser Lys Lys Tyr Asp Thr Met Arg Ser Lys Ile Tyr Ser Leu
385 390 395 400
Ile Asp Phe Met Ile Tyr Arg Lys Phe Ser Glu Asn His Val Ala Val
405 410 415
Asp Asp Phe Val Glu Glu Leu Arg Ser Leu Leu Thr Glu Asp Glu Lys
420 425 430
Glu Ser Ala Tyr Ser Arg Trp Ala Glu Thr Leu Ile Asn Asp Gly Phe
435 440 445
Ala Gln Glu Ile Leu Val Lys Leu Leu Pro Gln Thr Asp Pro Ala Val
450 455 460
Ile Gly Lys Ile Lys Gly Lys Lys Leu Leu Asn Asp Ser Ile Ala Gly
465 470 475 480
Ile Lys Leu Lys Lys Asp Ala Ser Phe Phe Thr Lys Ile Ile Asn Val
485 490 495
Leu Cys Met Phe Gln Asp Gly Lys Glu Ile Asn Glu Leu Val Ser Ser
500 505 510
Leu Val Asn Lys Phe Ala Asn Ile Gln Ser Phe Val Asp Val Met Arg
515 520 525
Ser Gln Gly Ile Asp Ser Gly Phe Thr Ala Asp Tyr Ala Met Phe Ala
530 535 540
Glu Ser Gly Arg Ile Ser Arg Glu Leu His Ile Leu Lys Gly Ile Ala
545 550 555 560
Arg Met Gln His Ser Ile Ala Gly Leu Gly Asp Val Lys Ile Tyr Gly
565 570 575
Ser Asp Asp Lys Phe His Gly Val Ser Arg Arg Val Tyr Thr Asp Ala
580 585 590
Ala Tyr Ile Leu Gly Phe Gly Glu Arg Ser Glu Asp Asn Asp Gly Tyr
595 600 605
Val Asp Asp Tyr Val Ser Ser Lys Leu Leu Gly Gly Ala Asp Lys Asn
610 615 620
Leu Arg Asn Phe Ile Thr Asn Asn Val Ile Lys Asn Arg Arg Phe Leu
625 630 635 640
Tyr Thr Val Arg Tyr Met Asn Pro Lys Arg Ala Lys Lys Leu Val Gln
645 650 655
Asn Asp Ala Leu Val Val Leu Ala Leu Ser Gly Ile Pro Glu Thr Gln
660 665 670
Ile Asp Arg Tyr Tyr Lys Ser Cys Ile Glu Lys Arg Ser Phe Asn Pro
675 680 685
Asp Leu Asn Glu Lys Ile Ala Ala Leu Ser Glu Met Ile Thr Thr Leu
690 695 700
Lys Ile Asp Asp Phe Glu Asp Val Lys Gln Asn Pro Glu Lys Asn Ala
705 710 715 720
Asn Tyr Glu Ala Lys Lys Asn Gln Arg Ile Ser Lys Glu Arg Tyr Lys
725 730 735
Ala Cys Ile Gly Leu Tyr Leu Thr Val Leu Tyr Leu Ile Cys Lys Asn
740 745 750
Leu Val Lys Ile Asn Ala Arg Tyr Ser Ile Ala Ile Gly Cys Leu Glu
755 760 765
Arg Asp Thr Gln Leu His Gly Val Asp Phe Lys Gly Ala Ala Tyr Met
770 775 780
Thr Arg Asp Val Phe Ile Ala Lys Gly Trp Ile Asn Pro Lys Lys Pro
785 790 795 800
Thr Val Lys Ser Ile Lys Glu Gln Tyr Ala Phe Leu Thr Pro Tyr Ile
805 810 815
Phe Thr Thr Tyr Arg Asn Met Ile Ala His Leu Ala Ala Val Thr Asn
820 825 830
Ala Tyr Lys Tyr Ile Pro Gln Met Asp Arg Phe Lys Ser Trp Phe His
835 840 845
Leu Tyr His Thr Val Ile Gln His Ser Leu Ile Gln Gln Tyr Glu Tyr
850 855 860
Asp Arg Asp Tyr Gly Arg Lys Gly Ala Pro Val Val Ser Glu Arg Val
865 870 875 880
Leu Gln Leu Leu Glu Gln Cys Arg Glu His Ser Asn Tyr Ser Arg Asp
885 890 895
Leu Leu His Ile Leu Asn Leu Pro Phe Gly Tyr Asn Leu Pro Arg Tyr
900 905 910
Leu Asn Leu Ser Ser Glu Lys Tyr Phe Asp Ala Asn Ala Ile
915 920 925
<210> 101
<211> 1030
<212> PRT
<213> 未知的
<220>
<223> 重叠群emb OGPN01002610.1
<400> 101
Met Ala Lys Lys Ile Thr Ala Lys Gln Lys Arg Glu Glu Lys Glu Arg
1 5 10 15
Leu Asn Lys Gln Lys Trp Ala Lys Gln Asp Thr Pro Val Val Pro Lys
20 25 30
Ser Lys Thr Glu Glu Lys Pro Val Ala Ala Ser Asp Asp Lys Leu Leu
35 40 45
Lys Thr Thr Gln Val Lys Lys Val Gln Thr Lys Ser Lys Ala Lys Ala
50 55 60
Met Gly Leu Lys Thr Val Leu Ser Phe Asp Asp Lys Ile Ala Ile Ala
65 70 75 80
Ser Phe Val Asn Asp Lys Lys Thr Lys Leu Pro His Ile Glu Arg Ile
85 90 95
Thr Asp Lys Ser Gly Thr Thr Ile His Glu Asn Ala Arg Met Phe Asp
100 105 110
Ser Ser Val Asp Glu Gln Asn Val Asn Ile Glu Lys Arg Met Thr Ile
115 120 125
Glu Glu Lys Gln Asn Asp Gly Thr Phe Lys Lys Asp Glu Lys Asp Val
130 135 140
Lys Ala Thr Ile Cys Asn Pro Tyr Phe Lys Thr Cys Gly Lys Asp Tyr
145 150 155 160
Ile Gly Ile Lys Asp Val Ala Glu Lys Tyr Phe Phe Gly Lys Thr Phe
165 170 175
Pro Asn Glu Asn Leu Arg Val Gln Ile Ala Tyr Asn Val Phe Asp Ile
180 185 190
Gln Lys Ile Leu Gly Thr Tyr Val Asn Asn Ile Ile Tyr Ser Phe Tyr
195 200 205
Asn Leu Arg Arg Asp Gly Lys Ser Asp Val Asp Ile Ile Gly Ser Leu
210 215 220
Tyr Ala Phe Ala Asp Phe Asp Asn Gln Leu Lys Asp Lys Pro Ala Phe
225 230 235 240
Arg Glu Ala Lys Asp Leu Leu Lys Asn Thr Glu Ala Tyr Phe Ser Tyr
245 250 255
Phe Gly Asp Val Phe Lys Lys Ser Lys Lys Gly Lys Lys Asp Glu Asn
260 265 270
Asn Glu Asp Tyr Glu Lys Asn Leu Arg His Asn Phe Asn Val Leu Arg
275 280 285
Val Leu Ser Phe Leu Arg Gln Ile Cys Thr His Ala Tyr Val Lys Cys
290 295 300
Thr Gly Gly Ala Lys Asn Asn Gly Asp Ser Thr Lys Val Glu Ala Glu
305 310 315 320
Ser Leu Asp Ala Leu Phe Asn Ile Thr Glu Tyr Phe Ala Lys Thr Ala
325 330 335
Pro Glu Leu Ser Lys Thr Ile Asn Glu Ile Tyr Lys Glu Gly Ile Asp
340 345 350
Arg Ile Asn Asn Asp Phe Val Thr Asn Gly Lys Asn Asn Leu Tyr Ile
355 360 365
Leu Ser Lys Val Tyr Pro Asp Met Gln Arg Asn Glu Leu Val Lys Lys
370 375 380
Tyr Tyr Gln Phe Val Val Cys Lys Glu Gly Asn Asn Val Gly Ile Asn
385 390 395 400
Thr Arg Lys Leu Lys Glu Ser Ile Ile Ser Gln His Pro Trp Ile Thr
405 410 415
Thr Pro Gln Asp Asn Asn Lys Ala Asn Asp Tyr Glu Ser Cys Arg His
420 425 430
Lys Leu Tyr Thr Ile Met Cys Phe Ile Leu Val Ala Glu Leu Asp Ala
435 440 445
His Glu Ser Ile Arg Asp Asn Met Val Ala Glu Leu Arg Ala Asn Met
450 455 460
Asp Gly Asp Asp Gly Arg Asp Ala Ile Tyr Glu Lys Tyr Ala Lys Asp
465 470 475 480
Ile Tyr His Ile Val Lys Asp Lys Leu Leu Ala Met Gln Lys Val Phe
485 490 495
Asp Glu Glu Leu Val Pro Val Lys Val Glu Gly Lys Asn Asp Pro Gln
500 505 510
Gln Phe Thr His Gly Lys Leu Gly Lys Lys Glu Ile Glu Ser Phe Cys
515 520 525
Leu Ser Asp Lys Asn Thr Ser Asp Ile Ala Lys Val Val Tyr Phe Leu
530 535 540
Cys Asn Phe Leu Asp Gly Lys Glu Ile Asn Glu Leu Cys Cys Ala Met
545 550 555 560
Met Asn Lys Phe Asp Gly Ile Gly Asp Leu Ile Asp Thr Ala Lys Gln
565 570 575
Cys Gly Glu Glu Val Lys Phe Ile Glu Glu Phe Ala Cys Leu Ser Asn
580 585 590
Cys Arg Lys Ile Thr Asn Asp Ile Arg Val Ala Lys Ser Ile Ser Lys
595 600 605
Met Lys Asn Lys Val Asn Ile Asp Asn Asp Ile Ile Tyr Leu Asp Ala
610 615 620
Ile Glu Leu Leu Gly Arg Lys Ile Glu Lys Tyr Gln Lys Asp Glu Asn
625 630 635 640
Gly Lys Ile Leu Leu Gly Thr Asp Gly Lys Arg Leu Tyr Thr Gln Glu
645 650 655
Tyr Lys Tyr Phe Asn Asp Met Phe Phe Asn Ala Gly Asn His Lys Val
660 665 670
Arg Asn Phe Ile Ala Asn Asn Val Met Gln Ser Lys Trp Phe Phe Tyr
675 680 685
Val Val Arg Tyr Asn Lys Pro Ala Glu Cys Gln Ile Ile Met Arg Asn
690 695 700
Lys Thr Leu Val Lys Phe Thr Leu Asp Asp Leu Pro Asp Met Gln Ile
705 710 715 720
Gln Arg Tyr Tyr Ser Ser Val Phe Gly Asp Asn Asn Met Pro Ala Val
725 730 735
Asp Glu Met Arg Lys Arg Leu Leu Asp Lys Ile Asn Gln Phe Ser Val
740 745 750
Arg Gly Phe Leu Asp Glu Leu Asp Glu Ile Val Leu Met Ser Asp Glu
755 760 765
Glu Ser Lys Arg Asn Lys Ser Ser Glu Lys Glu Gln Lys Lys Ser Leu
770 775 780
Ile Arg Leu Tyr Leu Thr Ile Ala Tyr Leu Ile Thr Lys Ser Met Val
785 790 795 800
Lys Ile Asn Thr Arg Phe Ser Ile Ala Cys Ala Met Tyr Glu Arg Asp
805 810 815
Tyr Ala Leu Leu Cys Gln Ser Glu Met Lys Gly Gly Pro Trp Asp Gly
820 825 830
Gly Ala Gln Ala Leu Ala Val Thr Arg Lys Phe Leu Asn His Asp Arg
835 840 845
Glu Val Phe Asp Arg Tyr Cys Ala Arg Glu Ala Glu Ile Ala Arg Leu
850 855 860
Pro Ser Glu Glu Arg Lys Pro Leu Arg Lys Ala Asn Asp Lys Leu Leu
865 870 875 880
Lys Gln Thr His Tyr Thr Asn His Ser Tyr Thr Tyr Ile Val Asn Asn
885 890 895
Leu Asn Ser Phe Thr Asp Ile Asp Tyr Cys Ala Lys Asp Val Gly Leu
900 905 910
Pro Ala Pro Asn Asp Lys Asn Asp Asn Ala Ser Ile Leu Gly Glu Met
915 920 925
Arg Asn Asp Ile Ala His Leu Asn Ile Val His Asp Met Val Lys Tyr
930 935 940
Ile Glu Glu Leu Lys Asp Ile Ser Ser Tyr Tyr Ala Phe Tyr Cys Tyr
945 950 955 960
Val Leu Gln Arg Arg Leu Val Gly Lys Asp Pro Asn Cys Gln Asn Lys
965 970 975
Phe Lys Ala Lys Tyr Ala Lys Glu Leu Asn Asp Tyr Gly Thr Tyr Asn
980 985 990
Lys Asn Leu Met Trp Met Leu Asn Leu Pro Phe Ala Tyr Asn Leu Pro
995 1000 1005
Arg Tyr Lys Asn Leu Ser Ser Glu Phe Leu Phe Tyr Asp Met Glu
1010 1015 1020
Tyr Asn Lys Lys Asp Asp Glu
1025 1030
<210> 102
<211> 1027
<212> PRT
<213> 未知的
<220>
<223> 重叠群emb OBLI01020244
<400> 102
Met Ala Lys Lys Ile Thr Ala Lys Gln Arg Arg Glu Glu Arg Glu Arg
1 5 10 15
Gln Asn Lys Gln Lys Trp Ala Lys Lys Gln Ala Asp Ala Thr Ala Val
20 25 30
Phe Glu Cys Glu Ala Asp Ile Lys Pro Ala Asp Ser Lys Asp Glu Asp
35 40 45
Cys Thr Asn Ile Tyr Ile Lys Arg Glu Lys Lys Lys Thr Gln Ala Lys
50 55 60
Ala Met Gly Leu Lys Thr Val Leu Gly Phe Asp Asn Lys Ile Ala Ile
65 70 75 80
Ala Ser Phe Met Ser Ser Lys Asp Ser Lys Ser Ser His Ile Glu Arg
85 90 95
Ile Thr Asp Pro Asn Gly Lys Thr Ile Arg Glu Asp Val Arg Met Phe
100 105 110
Asp Ser Asn Val Asp Glu Cys Ser Ile Asn Leu Glu Lys Arg Met Thr
115 120 125
Val Glu Glu Arg Gln Lys Asp Gly Thr Ile Lys Lys Asp Glu Lys Asp
130 135 140
Val Lys Ser Thr Ile Cys Asn Pro Tyr Ser Asn Glu Cys Gly Lys Asp
145 150 155 160
Tyr Ile Gly Ile Lys Ser Val Ala Glu Glu Leu Phe Phe Gly Arg Thr
165 170 175
Phe Pro Asn Asp Asn Leu Arg Val Gln Ile Ala Tyr Asn Ile Phe Asp
180 185 190
Ile Gln Lys Ile Leu Gly Thr Tyr Ile Asn Asn Ile Ile Tyr Ser Phe
195 200 205
Tyr Asn Leu Ser Arg Asp Glu Ser Gln Ser Asp Asn Asp Val Ile Gly
210 215 220
Thr Leu Tyr Met Leu Lys Asp Phe Asp Gly Gln Lys Glu Thr Asp Thr
225 230 235 240
Phe Arg Gln Ala Arg Ala Leu Leu Glu Arg Thr Glu Ala Tyr Tyr Ser
245 250 255
Tyr Phe Asp Asn Val Phe Lys Lys Ile Asp Lys Asn Lys Lys Lys Ser
260 265 270
Asp Asp Cys Lys Arg Glu Arg Asn Glu Ile Leu Arg Tyr Asn Phe Asn
275 280 285
Val Leu Arg Val Leu Ser Phe Leu Arg Gln Ile Cys Ala His Ala Gln
290 295 300
Val Lys Ile Ser Asn Glu His Asp Arg Glu Lys Gly Gly Gly Leu Val
305 310 315 320
Asp Ser Leu Asp Ala Leu Phe Asn Ile Ser Arg Phe Phe Asp Ala Val
325 330 335
Ala Pro Glu Leu Asn Glu Val Ile Asn Ser Val Tyr Ser Lys Gly Ile
340 345 350
Asp Asp Ile Asn Asp Asn Phe Val Lys Asn Gly Lys Asn Asn Phe Tyr
355 360 365
Ile Leu Ser Lys Ile Tyr Pro Glu Val Ala Arg Glu Asp Leu Leu Arg
370 375 380
Glu Tyr Tyr Tyr Phe Val Val Ser Lys Glu Gly Asn Asn Ile Gly Ile
385 390 395 400
Ser Thr Lys Lys Leu Lys Glu Ala Ile Ile Val Gln Asp Met Ser Tyr
405 410 415
Ile Lys Ser Glu Asp Tyr Asp Thr Tyr Arg Asn Lys Leu Tyr Thr Val
420 425 430
Leu Cys Phe Ile Leu Val Lys Glu Leu Asn Glu Arg Thr Thr Ile Arg
435 440 445
Glu Gln Met Val Ala Asp Leu Arg Ala Asn Met Asn Gly Asp Ile Gly
450 455 460
Arg Glu Asp Ile Tyr Ser Lys Tyr Ala Lys Ile Ile Tyr Ala Gln Val
465 470 475 480
Lys Pro Arg Phe Asp Thr Met Lys Ser Ala Phe Glu Glu Glu Ala Lys
485 490 495
Asp Val Ile Val Pro Asp Lys Lys Lys Pro Val Lys Phe Ser His Gly
500 505 510
Lys Leu Asp Lys Asn Glu Ile Glu Arg Phe Cys Ile Thr Ser Ala Asn
515 520 525
Thr Asp Ser Val Ala Lys Ile Ile Tyr Phe Leu Cys Lys Phe Leu Asp
530 535 540
Gly Lys Glu Ile Asn Glu Leu Cys Cys Ala Met Met Asn Lys Leu Asp
545 550 555 560
Gly Ile Asn Asp Leu Ile Glu Thr Ala Glu Gln Cys Gly Ala Lys Val
565 570 575
Glu Phe Val Asp Lys Phe Ser Val Leu Ser Asn Cys Glu Thr Ile Ser
580 585 590
Asp Gln Ile Arg Ile Val Lys Ser Ile Ser Lys Met Lys Lys Glu Ile
595 600 605
Ala Ile Asp Asn Asp Thr Ile Phe Leu Asp Ala Leu Glu Leu Leu Gly
610 615 620
Arg Lys Ile Asp Lys Tyr Lys Lys Asp Ala Thr Gly Lys Tyr Leu Lys
625 630 635 640
Asp Glu Asn Gly Lys Tyr Leu Tyr Ser Lys Glu Tyr Asp Asp Phe Gln
645 650 655
Tyr Met Phe Phe Lys Asp Ser His Arg Val Arg Asn Phe Ile Ser Asn
660 665 670
Ser Val Ile Lys Ser Lys Trp Phe Ser Tyr Ile Val Arg Tyr Asn Gln
675 680 685
Pro Ser Glu Cys Arg Ala Ile Met Lys Asn Lys Thr Leu Val Lys Phe
690 695 700
Ala Leu Asp Glu Leu Pro Asp Leu Gln Ile Gln Arg Tyr Phe Val Ala
705 710 715 720
Leu Tyr Gly Asp Glu Asp Leu Pro Ser Tyr Gly Glu Met Arg Lys Ile
725 730 735
Leu Leu Lys Lys Leu His Asp Phe Ser Ile Lys Gly Phe Leu Asp Glu
740 745 750
Ile Val Leu Leu Ser Asp Leu Asp Met Glu Ser Gln Asp Lys Tyr Cys
755 760 765
Glu Lys Glu Gln Lys Lys Ser Leu Phe Arg Leu Tyr Leu Thr Ile Ala
770 775 780
Tyr Leu Ile Thr Lys Ser Met Val Lys Ile Asn Thr Arg Phe Ser Ile
785 790 795 800
Ala Cys Ala Thr Tyr Glu Arg Asp Tyr Ala Leu Leu Cys Ala Ser Asn
805 810 815
Lys Gln Glu Arg Ala Trp Ser Ser Gly Ala Thr Ala Leu Ala Leu Thr
820 825 830
Arg Arg Phe Leu Asn Gln Asp Lys Leu Ile Phe Glu Lys His Tyr Ala
835 840 845
Arg Glu Gly Glu Ile Ser Lys Leu Pro Lys Glu Glu Arg Lys Ala Met
850 855 860
Arg Lys Val Asn Asp Gln Leu Leu Lys Arg Thr His Phe Ser Lys His
865 870 875 880
Ser Tyr Cys Tyr Ile Val Asp Asn Val Asn Arg Leu Thr Gly Gly Glu
885 890 895
Cys Arg Thr Asp Lys Arg Val Leu Pro Val Leu Asn Glu Lys Asn Asp
900 905 910
Asn Ala Gly Ile Leu Leu Asp Phe Arg Lys Thr Ile Ala His Leu Asn
915 920 925
Val Val His Lys Met Val Asp Tyr Val Asp Glu Ile Lys Gly Ile Thr
930 935 940
Ser Tyr Tyr Ala Phe Phe Cys Tyr Val Leu Gln Arg Met Leu Val Gly
945 950 955 960
Asn Asn Leu Asn Glu Lys Asn Ala Ile Lys Glu Lys Tyr Ser Ala Thr
965 970 975
Val Lys Ser Phe Gly Thr Tyr Ser Lys Asp Phe Met Trp Leu Ile Asn
980 985 990
Leu Pro Phe Ala Tyr Asn Leu Pro Arg Tyr Lys Asn Leu Ser Asn Glu
995 1000 1005
Gln Leu Phe Tyr Asp Glu Glu Glu Arg Asn Glu Thr Glu Glu Gln
1010 1015 1020
Ile Asp Arg Leu
1025
<210> 103
<211> 961
<212> PRT
<213> 未知的
<220>
<223> 重叠群OIZX01000427.1
<400> 103
Met Ala Lys Lys Lys Lys Thr Ala Arg Gln Leu Arg Glu Glu Met Gln
1 5 10 15
Gln Gln Arg Lys Gln Ala Ile Gln Lys Gln Gln Glu Gln Arg Gln Glu
20 25 30
Lys Ala Ala Ala Ala Arg Glu Thr Ala Ala Pro Glu Gln Pro Ala Ala
35 40 45
Ala Pro Val Pro Lys Arg Gln Arg Lys Ser Leu Ala Lys Ala Ala Gly
50 55 60
Leu Lys Ser Asn Phe Ile Leu Asp Pro Gln Arg Arg Thr Thr Val Met
65 70 75 80
Thr Ala Phe Gly Gln Gly Ser Thr Ala Ile Leu Glu Lys Gln Ile Val
85 90 95
Asp Arg Ala Ile Ser Asp Leu Gln Pro Val Gln Gln Phe Gln Val Glu
100 105 110
Pro Ala Ser Ala Ala Lys Tyr Arg Leu Lys Asn Ser Arg Val Arg Phe
115 120 125
Pro Asn Val Thr Ala Asp Asp Pro Leu Tyr Arg Arg Lys Asp Gly Gly
130 135 140
Phe Val Pro Gly Met Asp Ala Leu Arg Arg Lys Asn Val Leu Glu Gln
145 150 155 160
Arg Phe Phe Gly Lys Ser Phe Ala Asp Asn Ile His Ile Gln Met Ile
165 170 175
Tyr Ser Ile Leu Asp Ile His Lys Ile Leu Ala Ala Ala Ser Gly His
180 185 190
Ile Val His Leu Leu Asn Ile Val Asn Gly Ser Lys Asp Arg Asp Phe
195 200 205
Ile Gly Met Leu Ala Ala His Val Leu Tyr Asn Glu Leu Asn Glu Glu
210 215 220
Ala Lys Arg Ser Ile Ala Asp Phe Cys Lys Ser Pro Arg Leu Ile Tyr
225 230 235 240
Tyr Ser Ala Ala Phe Tyr Glu Thr Leu Asp Asn Gly Lys Ser Glu Arg
245 250 255
Arg Ser Asn Glu Asp Ile Phe Asn Ile Leu Ala Leu Met Thr Cys Leu
260 265 270
Arg Asn Phe Ser Ser His His Ser Ile Ala Ile Lys Val Lys Asp Tyr
275 280 285
Ser Ala Ala Gly Leu Tyr Asn Leu Arg Arg Leu Gly Pro Asp Met Lys
290 295 300
Lys Met Leu Asp Thr Phe Tyr Thr Glu Ala Phe Ile Gln Leu Asn Gln
305 310 315 320
Ser Phe Gln Asp His Asn Thr Thr Asn Leu Thr Cys Leu Phe Asp Ile
325 330 335
Leu Asn Ile Ser Asp Ser Ala Arg Gln Lys Gln Leu Ala Glu Glu Phe
340 345 350
Tyr Arg Tyr Val Val Phe Lys Glu Gln Lys Asn Leu Gly Phe Ser Val
355 360 365
Arg Lys Leu Arg Glu Glu Met Leu Leu Leu Pro Asp Ala Ala Val Ile
370 375 380
Ala Asp Lys Arg Tyr Asp Thr Cys Arg Ser Lys Leu Tyr Asn Leu Met
385 390 395 400
Asp Phe Leu Ile Leu Arg Val Tyr Arg Thr Gly Arg Ala Asp Arg Cys
405 410 415
Asp Lys Leu Pro Glu Ala Leu Arg Ala Ala Leu Thr Asp Glu Glu Lys
420 425 430
Ala Val Val Tyr His Lys Glu Ala Leu Ser Leu Trp Asn Glu Met Arg
435 440 445
Thr Leu Ile Leu Asp Gly Leu Leu Pro Gln Met Thr Pro Glu Asn Leu
450 455 460
Ser Arg Leu Ser Gly Gln Lys Arg Lys Gly Glu Leu Ser Leu Asp Asp
465 470 475 480
Ala Met Leu Lys Glu Cys Leu Tyr Glu Pro Gly Pro Val Pro Glu Asp
485 490 495
Ala Ala Pro Glu Glu Ala Asn Ala Glu Tyr Phe Cys Arg Met Ile Tyr
500 505 510
Leu Ala Thr Leu Phe Met Asp Gly Lys Glu Ile Asn Thr Leu Leu Thr
515 520 525
Thr Leu Ile Ser Lys Phe Glu Asn Ile Ala Ala Phe Leu Gln Thr Met
530 535 540
Glu Gln Leu Asn Ile Glu Ala Glu Leu Gly Pro Glu Tyr Ala Met Phe
545 550 555 560
Thr Arg Ser Arg Ala Val Ala Glu Gln Leu Arg Val Ile Asn Ser Phe
565 570 575
Ala Leu Met Lys Lys Pro Gln Val Asn Ala Lys Gln Gln Leu Tyr Arg
580 585 590
Ala Ala Val Thr Leu Leu Gly Thr Glu Asp Pro Asp Gly Val Thr Asp
595 600 605
Glu Met Leu Cys Ile Asp Pro Val Thr Gly Lys Met Leu Pro Pro Asn
610 615 620
Gln Arg His His Gly Asp Thr Gly Leu Arg Asn Phe Ile Ala Asn Asn
625 630 635 640
Val Val Glu Ser Arg Arg Phe Gln Tyr Leu Ile Arg Tyr Ser Asp Pro
645 650 655
Ala Gln Leu His Gln Leu Ala Ser Asn Lys Lys Leu Val Arg Phe Val
660 665 670
Leu Ser Ser Ile Pro Asp Thr Gln Ile Asn Arg Tyr Tyr Glu Thr Cys
675 680 685
Gly Gln Thr Arg Leu Ala Gly Arg Ala Ala Lys Val Glu Phe Leu Thr
690 695 700
Asp Met Ile Ala Ala Ile Arg Phe Asp Gln Phe Arg Asp Val Asn Gln
705 710 715 720
Lys Glu Arg Gly Ala Asn Thr Gln Lys Glu Arg Tyr Lys Ala Met Leu
725 730 735
Gly Leu Tyr Gln Thr Val Leu Tyr Leu Ala Val Lys Asn Leu Val Asn
740 745 750
Ile Asn Ala Arg Tyr Val Met Ala Phe His Cys Val Glu Arg Asp Met
755 760 765
Phe Leu Tyr Asp Gly Glu Leu Thr Asp Pro Lys Gly Glu Ser Val Ser
770 775 780
Ala Phe Leu Ala Val Asn Gly Lys Lys Gly Val Gln Pro Gln Tyr Leu
785 790 795 800
Leu Leu Thr Gln Leu Phe Ile Arg Arg Asp Tyr Leu Lys Arg Ser Ala
805 810 815
Cys Glu Gln Ile Gln His Asn Met Glu Asn Ile Ser Asp Arg Leu Leu
820 825 830
Arg Glu Tyr Arg Asn Ala Val Ala His Leu Asn Val Ile Ala His Leu
835 840 845
Ala Asp Tyr Ser Ala Asp Met Arg Glu Ile Thr Ser Tyr Tyr Gly Leu
850 855 860
Tyr His Tyr Leu Met Gln Arg His Leu Phe Lys Arg His Ala Trp Gln
865 870 875 880
Ile Arg Gln Pro Glu Arg Pro Thr Glu Glu Glu Gln Lys Leu Ile Glu
885 890 895
Gln Glu Gln Lys Gln Leu Ala Trp Glu Lys Ala Leu Phe Asp Lys Thr
900 905 910
Leu Gln Tyr His Ser Tyr Asn Lys Asp Leu Val Lys Ala Leu Asn Ala
915 920 925
Pro Phe Gly Tyr Asn Leu Ala Arg Tyr Lys Asn Leu Ser Ile Glu Pro
930 935 940
Leu Phe Ser Lys Glu Ala Ala Pro Ala Ala Glu Ile Lys Ala Thr His
945 950 955 960
Ala
<210> 104
<211> 911
<212> PRT
<213> 未知的
<220>
<223> 重叠群OCTW011587266.1
<400> 104
Met Lys Gln Asn Asp Arg Glu Asn Asn Asn Lys Ile Lys Lys Ser Ala
1 5 10 15
Ala Lys Ala Val Gly Val Lys Ser Leu Ala Arg Leu Ser Asp Gly Ser
20 25 30
Thr Val Val Ser Ser Phe Gly Lys Gly Ala Ala Ala Glu Leu Glu Ser
35 40 45
Leu Ile Thr Gly Gly Glu Ile Arg Lys Leu Ser Asp Lys Ala Ile Leu
50 55 60
Glu Ile Thr Asp Asp Thr Gln Asn Lys Asn Ala Tyr Asn Val Lys Ser
65 70 75 80
Ser Arg Ile Pro Asn Leu Thr Ala Arg Thr Asp Lys Leu Ser Asp Lys
85 90 95
Ser Gly Met Asp Asp Leu Gly Phe Lys Arg Glu Leu Glu Leu Glu Val
100 105 110
Phe Gly Gln Cys Phe Asp Asp Ser Ile His Ile Gln Ile Ala His Ala
115 120 125
Val Phe Asp Ile Gln Lys Ser Leu Ala Ala Val Ile Pro Asn Val Leu
130 135 140
Tyr Thr Leu Asn Asn Leu Asp Arg Ser Tyr Ser Thr Asp Asn Thr Ser
145 150 155 160
Asp Lys Lys Asp Ile Ile Gly Asn Thr Leu Asn Tyr Gln His Ser Tyr
165 170 175
Glu Ser Phe Asn Val Glu Lys Arg Gly Glu Phe Thr Glu Tyr Tyr Asn
180 185 190
Ala Ala Lys Asp Arg Phe Ser Tyr Phe Pro Asp Ile Leu Cys Val Leu
195 200 205
Glu Lys Val Asn Gly Lys Asp Arg Tyr Gln Pro Lys Ser Glu Lys Asp
210 215 220
Ala Phe Asn Val Leu Ser Ser Val Asn Met Leu Arg Asn Ser Leu Phe
225 230 235 240
His Phe Ala Pro Lys Ser Asn Asp Gly Lys Ala Arg Ile Ala Val Phe
245 250 255
Lys Asn Gln Phe Asp Ser Asp Phe Ser His Ile Thr Ser Thr Val Asn
260 265 270
Lys Ile Tyr Ser Ala Lys Ile Ala Gly Val Asn Glu Asn Phe Leu Asn
275 280 285
Asn Glu Gly Asn Asn Leu Tyr Ile Ile Leu Lys Ala Thr Asn Trp Asp
290 295 300
Ile Lys Lys Ile Val Pro Gln Leu Tyr Arg Phe Ser Val Leu Lys Ser
305 310 315 320
Asp Lys Asn Met Gly Phe Asn Met Arg Lys Leu Arg Glu Phe Ala Val
325 330 335
Glu Ser Lys Asn Ile Asp Leu Ser Arg Leu Asn Asp Lys Phe Leu Thr
340 345 350
Asn Asn Arg Lys Lys Leu Tyr Lys Val Ile Asp Phe Ile Ile Tyr Tyr
355 360 365
His Leu Asn Lys Val Leu Lys Asp Ser Phe Val Asp Asp Phe Val Ala
370 375 380
Ala Leu Arg Ala Ser Gln Ser Glu Glu Glu Lys Glu Lys Leu Tyr Ala
385 390 395 400
Gln Tyr Ser Glu Arg Leu Phe Ala Asp Glu Gly Leu Lys Ser Ala Ile
405 410 415
Lys Lys Ala Val Asp Met Ile Ser Asp Thr Lys Ser Asn Ile Phe Lys
420 425 430
Met Lys Thr Pro Leu Asp Lys Ala Leu Ile Glu Asn Ile Lys Val Asn
435 440 445
Ser Asp Ala Ser Asp Phe Cys Lys Leu Ile Tyr Val Phe Thr Arg Phe
450 455 460
Leu Asp Gly Lys Glu Ile Asn Ile Leu Leu Asn Ser Leu Ile Lys Lys
465 470 475 480
Phe Gln Asp Ile His Ser Phe Asn Thr Thr Val Lys Lys Leu Ser Glu
485 490 495
Asn Asn Leu Ile Ile Asn Ala Asp Tyr Val Asp Asp Tyr Ser Leu Phe
500 505 510
Glu Gln Ser Gly Thr Val Ala Arg Glu Leu Met Leu Ile Lys Ser Ile
515 520 525
Ser Lys Met Asp Phe Gly Leu Asp Asn Ile Asn Leu Ser Phe Met Tyr
530 535 540
Asp Asp Ala Leu Arg Thr Leu Gly Val Ser Asp Glu Asn Leu Pro Glu
545 550 555 560
Val Lys Arg Glu Tyr Phe Gly Lys Thr Lys Asn Leu Ser Ala Tyr Ile
565 570 575
Arg Asn Asn Val Leu Glu Asn Arg Arg Phe Lys Tyr Val Ile Lys Tyr
580 585 590
Ile His Pro Ser Asp Val Gln Lys Ile Ala Cys Asn Lys Ala Ile Ala
595 600 605
Gly Phe Val Leu Asn Arg Met Pro Asp Thr Gln Ile Lys Arg Tyr Tyr
610 615 620
Asp Ser Leu Ile Asn Lys Gly Ala Thr Asp Ile Gln Ala Gln Ala Lys
625 630 635 640
Ala Leu Leu Asp Cys Ile Thr Gly Ile Ser Phe Asp Ala Ile Lys Asp
645 650 655
Asp Lys His Leu His Lys Ser Lys Glu Lys Ser Pro Gln Arg Ser Ala
660 665 670
Asp Arg Glu Arg Lys Lys Ala Met Leu Thr Leu Tyr Tyr Thr Ile Val
675 680 685
Tyr Ile Phe Val Lys Gln Met Leu His Ile Asn Ser Leu Tyr Thr Ile
690 695 700
Gly Phe Phe Tyr Leu Glu Arg Asp Gln Arg Phe Ile Tyr Ser Arg Ala
705 710 715 720
Lys Lys Glu Asn Lys Asn Pro Ser Lys Asn Ser Tyr Leu Asn Asp Phe
725 730 735
Arg Ser Val Thr Ala Tyr Phe Ile Pro Ser Glu Ile Met Lys Arg Ile
740 745 750
Glu Lys Asn Glu Asn Lys Gly Phe Leu Glu Asp Phe Glu Ala Leu Trp
755 760 765
Asn Ser Cys Gly Lys Thr Ser Arg Leu Arg Lys Glu Asp Val Leu Leu
770 775 780
Tyr Ala Arg Tyr Ile Ser Pro Asp His Ala Leu Lys Asn Tyr Lys Met
785 790 795 800
Ile Leu Asn Ser Tyr Arg Asn Lys Ile Ala His Ile Asn Val Ile Met
805 810 815
Ser Ala Gly Lys Tyr Thr Gly Gly Ile Lys Arg Met Asp Ser Tyr Phe
820 825 830
Ser Val Phe Gln His Leu Val Gln Cys Asp Ile Leu Ser Asn Pro Asn
835 840 845
Asn Lys Gly Lys Cys Phe Glu Ser Glu Ser Leu Lys Pro Leu Leu Leu
850 855 860
Asp Met Lys Phe Asp Gly Thr Asp Glu Lys Leu Tyr Ser Lys Arg Leu
865 870 875 880
Thr Arg Ala Leu Asn Ile Pro Phe Gly Tyr Asn Val Pro Arg Tyr Lys
885 890 895
Asn Leu Thr Phe Glu Lys Ile Tyr Leu Lys Ser Ser Ile Asn Glu
900 905 910
<210> 105
<211> 904
<212> PRT
<213> 未知的
<220>
<223> 重叠群emb OGNF01009141.1
<400> 105
Met Ala Asp Ile Asp Lys Lys Lys Ser Ser Ala Lys Ala Ala Gly Leu
1 5 10 15
Lys Ser Thr Phe Val Leu Glu Asn Asn Lys Leu Leu Met Thr Ser Phe
20 25 30
Gly Asn Gly Asn Lys Ala Val Ile Glu Lys Ile Ile Asp Glu Lys Val
35 40 45
Asp Ser Ile Asn Glu Pro Glu Val Phe Ser Val Thr Pro Cys Asp Lys
50 55 60
Lys Phe Glu Leu Gln Pro Ala Lys Arg Gly Leu Ala Ala Asp Ser Leu
65 70 75 80
Val Asp Asn Pro Leu Lys Ser Lys Lys Thr Ala Gly Asp Asp Ala Ile
85 90 95
His Ser Arg Lys Phe Leu Glu Arg Gln Phe Phe Asp Gly Asn Thr Phe
100 105 110
Asn Asp Asn Ile His Ile Gln Leu Ile Tyr Asn Ile Leu Asp Ile Glu
115 120 125
Lys Ile Leu Ser Val His Val Asn Asp Ile Val Tyr Ser Val Asn Asn
130 135 140
Ile Leu Ser Arg Gly Glu Gly Met Glu Tyr Asn Asp Tyr Ile Gly Thr
145 150 155 160
Leu Asn Leu Lys Ser Phe Glu Thr Tyr Lys Asn Asn Leu Val Asn Lys
165 170 175
Lys Lys Phe Asp Leu Asp Arg Val Lys Lys Ile Pro Gln Leu Ala Tyr
180 185 190
Phe Gly Ser Ala Phe Tyr Asn Thr Pro Glu Asp Thr Ser Ala Lys Ile
195 200 205
Thr Lys Thr Lys Ile Lys Ser Asn Glu Glu Ile Tyr Tyr Thr Phe Met
210 215 220
Leu Leu Ser Thr Ala Arg Asn Phe Ser Ala His Tyr Leu Asp Arg Asn
225 230 235 240
Arg Ala Lys Ser Ser Asp Ala Glu Asp Phe Asp Gly Thr Ser Val Ile
245 250 255
Met Tyr Asn Leu Asp Asn Glu Glu Leu Tyr Lys Lys Leu Tyr Asn Lys
260 265 270
Lys Val His Met Ala Leu Thr Gly Met Lys Lys Val Leu Asp Ala Asn
275 280 285
Phe Asn Lys Lys Val Glu His Leu Asn Asn Ser Phe Ile Lys Asn Ser
290 295 300
Ala Lys Asp Phe Val Ile Leu Cys Glu Val Leu Gly Ile Lys Ser Arg
305 310 315 320
Asp Glu Lys Thr Lys Phe Val Lys Asp Tyr Tyr Asp Phe Val Val Arg
325 330 335
Lys Asn Tyr Lys His Leu Gly Phe Ser Val Lys Glu Leu Arg Glu Leu
340 345 350
Leu Phe Ala Asn His Asp Ser Asn Lys Tyr Ile Lys Glu Phe Asp Lys
355 360 365
Ile Ser Asn Lys Lys Phe Asp Ser Val Arg Ser Arg Leu Asn Arg Leu
370 375 380
Ala Asp Tyr Ile Ile Tyr Asp Tyr Tyr Asn Lys Asn Asn Ala Lys Val
385 390 395 400
Ser Asp Leu Val Lys Tyr Leu Arg Ala Ala Ala Asp Asp Glu Gln Lys
405 410 415
Lys Lys Ile Tyr Leu Asn Glu Ser Ile Asn Leu Val Lys Ser Gly Ile
420 425 430
Leu Glu Arg Ile Lys Lys Ile Leu Pro Lys Leu Asn Gly Lys Ile Ile
435 440 445
Gly Asn Met Gln Pro Asp Ser Thr Ile Thr Ala Ser Met Leu His Asn
450 455 460
Thr Gly Lys Asp Trp His Pro Ile Ser Glu Asn Ala His Tyr Phe Thr
465 470 475 480
Lys Trp Ile Tyr Thr Leu Thr Leu Phe Met Asp Gly Lys Glu Ile Asn
485 490 495
Asp Leu Val Thr Thr Leu Ile Asn Lys Phe Asp Asn Ile Ala Ser Phe
500 505 510
Ile Glu Val Leu Lys Ser Gln Ser Val Cys Thr His Phe Ser Glu Glu
515 520 525
Arg Lys Met Phe Ile Asp Ser Ala Glu Ile Cys Ser Glu Leu Ser Ala
530 535 540
Met Asn Ser Phe Ala Arg Met Glu Ala Pro Gly Ala Ser Ser Lys Arg
545 550 555 560
Ala Met Phe Val Glu Ala Ala Arg Ile Leu Gly Asp Asn Arg Ser Lys
565 570 575
Glu Glu Leu Glu Glu Tyr Phe Asp Thr Leu Phe Asp Lys Ser Ala Ser
580 585 590
Lys Lys Glu Lys Gly Phe Arg Asn Phe Ile Arg Asn Asn Val Val Asp
595 600 605
Ser Asn Arg Phe Lys Tyr Leu Thr Arg Tyr Thr Asp Thr Ser Ser Val
610 615 620
Lys Ala Phe Ser Asn Asn Lys Ala Leu Val Lys Phe Ala Ile Lys Asp
625 630 635 640
Ile Pro Gln Glu Gln Ile Leu Arg Tyr Tyr Asn Ser Cys Phe Gly Ala
645 650 655
Ser Glu Arg Tyr Tyr Asn Asp Gly Met Ser Asp Lys Leu Val Glu Ala
660 665 670
Ile Gly Lys Ile Asn Leu Met Gln Phe Asn Gly Val Ile Gln Gln Ala
675 680 685
Asp Arg Asn Met Leu Pro Glu Glu Lys Lys Lys Ala Asn Ala Gln Lys
690 695 700
Glu Lys Tyr Lys Ser Ile Ile Arg Leu Tyr Leu Thr Val Cys Tyr Leu
705 710 715 720
Phe Phe Lys Asn Leu Val Tyr Val Asn Ser Arg Tyr Tyr Ser Ala Phe
725 730 735
Tyr Asn Leu Glu Lys Asp Arg Ser Leu Phe Glu Ile Asn Gly Glu Leu
740 745 750
Lys Pro Thr Gly Lys Phe Asp Glu Gly His Tyr Thr Gly Leu Val Lys
755 760 765
Leu Phe Ile Asp Asn Gly Trp Ile Asn Pro Arg Ala Ser Ala Tyr Leu
770 775 780
Thr Val Asn Leu Ala Asn Ser Asp Glu Thr Ala Ile Arg Thr Phe Arg
785 790 795 800
Asn Thr Ala Glu His Leu Glu Ala Leu Arg Asn Ala Asp Lys Tyr Leu
805 810 815
Asn Asp Leu Lys Gln Phe Asp Ser Tyr Phe Glu Ile Tyr His Tyr Ile
820 825 830
Thr Gln Arg Asn Ile Lys Glu Lys Cys Glu Met Leu Lys Glu Gln Thr
835 840 845
Val Lys Tyr Asn Asn Asp Leu Leu Lys Tyr His Gly Tyr Ser Lys Asp
850 855 860
Phe Val Lys Ala Leu Cys Val Pro Phe Gly Tyr Asn Leu Pro Arg Phe
865 870 875 880
Lys Asn Leu Ser Ile Asp Ala Leu Phe Asp Lys Asn Asp Lys Arg Glu
885 890 895
Lys Leu Lys Lys Gly Phe Glu Asp
900
<210> 106
<211> 933
<212> PRT
<213> 未知的
<220>
<223> 重叠群emb OIEN01002196.1
<400> 106
Met Glu Arg Gln Lys Arg Lys Met Lys Ser Lys Ser Lys Met Ala Gly
1 5 10 15
Val Lys Ser Val Phe Val Ile Gly Asp Glu Leu Leu Met Thr Ser Phe
20 25 30
Gly Asp Gly Asp Asp Ala Val Leu Glu Lys Asp Ile Asp Glu Asn Gly
35 40 45
Val Val Asn Asp Cys Arg Asn Pro Ala Ala Tyr Asp Ala Val Tyr Gly
50 55 60
Thr Asp Ser Ile Arg Val Lys Lys Thr Asn Asn Asn Ile Arg Ala Lys
65 70 75 80
Val Asn Asn Pro Leu Ala Lys Ser Asn Ile Arg Ser Glu Glu Ser Ala
85 90 95
Leu Phe Arg Thr Arg Val Asn Glu Tyr Lys Arg Glu Gln Lys Asp Lys
100 105 110
Tyr Glu Thr Leu Phe Phe Gly Lys Thr Phe Asp Asp Asn Ile His Ile
115 120 125
Gln Leu Ile Ser Lys Ile Leu Asp Ile Glu Lys Thr Phe Ser Val Val
130 135 140
Ile Gly Asn Ile Val Tyr Ala Ile Asn Asn Leu Ser Leu Glu Gln Ser
145 150 155 160
Ile Asp Arg Pro Ile Asp Ile Phe Gly Asp Lys Asn Thr Gln Gly Ile
165 170 175
Ser Leu Arg Glu Asp Asn Asp Tyr Leu Lys Thr Met Leu Pro Arg Cys
180 185 190
Glu Tyr Leu Phe His Asn Ile Leu Asn Ser Asp Ser Asp Asn Asn Ser
195 200 205
Lys Met Asn Tyr Asn Lys Val Asn Lys Gly Lys Glu Glu Lys Asp Asn
210 215 220
Arg Asn Asn Glu Asn Ile Glu Lys Leu Lys Lys Ala Leu Glu Val Ile
225 230 235 240
Lys Ile Ile Arg Val Asp Ser Phe His Gly Val Asp Gly Ile Lys Gly
245 250 255
Asp Gln Lys Phe Pro Arg Ser Lys Tyr Asn Leu Ala Val Asn Tyr Asn
260 265 270
Glu Glu Ile Gln Lys Thr Ile Ser Glu Pro Phe Asn Arg Lys Val Glu
275 280 285
Glu Val Gln Gln Asp Phe Tyr Arg Asn Ser Cys Val Asn Ile Asp Phe
290 295 300
Leu Lys Glu Ile Met Tyr Gly Ser Asn Tyr Thr Asp Arg Gly Ser Asp
305 310 315 320
Ser Leu Glu Cys Ser Tyr Phe Asn Phe Ala Ile Leu Lys Gln Asn Lys
325 330 335
Asn Met Gly Phe Ser Ile Thr Ser Ile Arg Glu Cys Leu Leu Asp Leu
340 345 350
Tyr Glu Leu Asn Phe Glu Ser Met Gln Asn Leu Arg Pro Arg Ala Asn
355 360 365
Ser Phe Cys Asp Phe Leu Ile Tyr Asp Tyr Tyr Cys Lys Asn Glu Ser
370 375 380
Glu Arg Ala Asn Leu Val Asp Cys Leu Arg Ser Ala Ala Ser Glu Glu
385 390 395 400
Glu Lys Lys Asn Ile Tyr Phe Gln Thr Ala Glu Arg Val Lys Glu Lys
405 410 415
Phe Arg Asn Ala Phe Asn Arg Ile Ser Arg Phe Asp Ala Ser Tyr Ile
420 425 430
Lys Asn Ser Arg Glu Lys Asn Leu Ser Gly Gly Ser Ser Leu Pro Lys
435 440 445
Tyr Ser Phe Ile Glu Gly Phe Thr Lys Arg Ser Lys Lys Ile Asn Asp
450 455 460
Asn Asp Glu Lys Asn Ala Asp Leu Phe Cys Asn Met Leu Tyr Tyr Leu
465 470 475 480
Ala Gln Phe Leu Asp Gly Lys Glu Ile Asn Ile Phe Leu Thr Ser Ile
485 490 495
His Asn Ile Phe Gln Asn Ile Asp Ser Phe Leu Lys Val Met Lys Glu
500 505 510
Lys Gly Met Glu Cys Lys Phe Gln Lys Asp Phe Lys Met Phe Ser His
515 520 525
Ala Gly His Val Ala Lys Lys Ile Glu Ile Val Ile Ser Leu Ala Lys
530 535 540
Met Lys Lys Thr Leu Asp Phe Tyr Asn Ala Gln Ala Leu Lys Asp Ala
545 550 555 560
Val Thr Ile Leu Gly Val Ser Lys Lys His Gln Tyr Leu Asp Met Asn
565 570 575
Ser Tyr Leu Asp Phe Tyr Met Phe Asp Asn Arg Ser Gly Ala Thr Gly
580 585 590
Lys Asn Ala Gly Lys Asp His Asn Leu Arg Asn Phe Leu Val Ser Asn
595 600 605
Val Ile Arg Ser Arg Lys Phe Asn Tyr Leu Ser Arg Tyr Ser Asn Leu
610 615 620
Ala Glu Val Lys Lys Leu Ala Gln Asn Pro Ser Leu Val Gln Phe Val
625 630 635 640
Leu Ser Arg Ile Glu Pro Ser Leu Ile Cys Arg Tyr Tyr Glu Ser Ser
645 650 655
Gln Gly Ile Ser Ser Glu Gly Ile Thr Ile Asp Glu Gln Ile Lys Lys
660 665 670
Leu Thr Gly Ile Ile Val Asp Met Asn Ile Asp Ser Phe Glu Asn Ile
675 680 685
Asn Asn Gly Glu Ile Gly Met Arg Tyr Ser Lys Ala Thr Pro Gln Ser
690 695 700
Ile Glu Arg Arg Asn Gln Met Arg Val Cys Val Gly Leu Tyr Leu Asn
705 710 715 720
Val Leu Tyr Gln Ile Glu Lys Asn Leu Met Asn Val Asn Ala Arg Tyr
725 730 735
Val Leu Ala Phe Ala Phe Ala Glu Arg Asp Ala Leu Met Leu Asn Phe
740 745 750
Thr Leu Glu Glu Cys Lys Lys Asn Lys Lys Arg Ser Ser Gly Gly Phe
755 760 765
Ser Phe Ile Glu Met Thr Gln Phe Phe Ile Asp Lys Lys Leu Phe Lys
770 775 780
Val Ala Thr Glu Ala Ile Lys Lys Asn Val Leu Lys Tyr Asn Gly Asn
785 790 795 800
Pro Glu Ser Leu Asn His Ile Pro Gly Glu Tyr Ile Cys Lys Asn Met
805 810 815
Glu Gly Tyr His Glu Asn Thr Val Arg Asn Phe Arg Asn Met Val Ala
820 825 830
His Leu Thr Ala Val Ala Arg Val Pro Leu Tyr Ile Ser Glu Val Thr
835 840 845
Gln Ile Asp Ser Tyr Tyr Ala Leu Tyr His Tyr Cys Met Gln Met Asn
850 855 860
Ile Leu Gln Gly Ile Glu Gln Ser Gly Lys Ile Leu Asp Asn Ile Lys
865 870 875 880
Leu Lys Asn Ala Leu Glu Asn Ala Arg Val His Arg Thr Tyr Ser Lys
885 890 895
Asp Ala Val Lys Tyr Leu Cys Leu Pro Phe Ala Tyr Asn Ile Ser Arg
900 905 910
Tyr Lys Ala Leu Thr Ile Lys Asp Leu Phe Asp Trp Thr Glu Tyr Ser
915 920 925
Cys Lys Lys Asp Glu
930
<210> 107
<211> 1034
<212> PRT
<213> 未知的
<220>
<223> 重叠群e-k87 11092736
<400> 107
Met Lys Arg Gln Lys Thr Phe Ala Lys Arg Ile Gly Ile Lys Ser Thr
1 5 10 15
Val Ala Tyr Gly Gln Gly Lys Tyr Ala Ile Thr Thr Phe Gly Lys Gly
20 25 30
Ser Lys Ala Glu Ile Ala Val Arg Ser Ala Asp Pro Pro Glu Glu Thr
35 40 45
Leu Pro Thr Glu Ser Asp Ala Thr Leu Ser Ile His Ala Lys Phe Ala
50 55 60
Lys Ala Gly Arg Asp Gly Arg Glu Phe Lys Cys Gly Asp Val Asp Glu
65 70 75 80
Thr Arg Ile His Thr Ser Arg Ser Glu Tyr Glu Ser Leu Ile Ser Asn
85 90 95
Pro Ala Glu Ser Pro Arg Glu Asp Tyr Leu Gly Leu Lys Gly Thr Leu
100 105 110
Glu Arg Lys Phe Phe Gly Asp Glu Tyr Pro Lys Asp Asn Leu Arg Ile
115 120 125
Gln Ile Ile Tyr Ser Ile Leu Asp Ile Gln Lys Ile Leu Gly Leu Tyr
130 135 140
Val Glu Asp Ile Leu His Phe Val Asp Gly Leu Gln Asp Glu Pro Glu
145 150 155 160
Asp Leu Val Gly Leu Gly Leu Gly Asp Glu Lys Met Gln Lys Leu Leu
165 170 175
Ser Lys Ala Leu Pro Tyr Met Gly Phe Phe Gly Ser Thr Asp Val Phe
180 185 190
Lys Val Thr Lys Lys Arg Glu Glu Arg Ala Ala Ala Asp Glu His Asn
195 200 205
Ala Lys Val Phe Arg Ala Leu Gly Ala Ile Arg Gln Lys Leu Ala His
210 215 220
Phe Lys Trp Lys Glu Ser Leu Ala Ile Phe Gly Ala Asn Ala Asn Met
225 230 235 240
Pro Ile Arg Phe Phe Gln Gly Ala Thr Gly Gly Arg Gln Leu Trp Asn
245 250 255
Asp Val Ile Ala Pro Leu Trp Lys Lys Arg Ile Glu Arg Val Arg Lys
260 265 270
Ser Phe Leu Ser Asn Ser Ala Lys Asn Leu Trp Val Leu Tyr Gln Val
275 280 285
Phe Lys Asp Asp Thr Asp Glu Lys Lys Lys Ala Arg Ala Arg Gln Tyr
290 295 300
Tyr His Phe Ser Val Leu Lys Glu Gly Lys Asn Leu Gly Phe Asn Leu
305 310 315 320
Thr Lys Thr Arg Glu Tyr Phe Leu Asp Lys Phe Phe Pro Ile Phe His
325 330 335
Ser Ser Ala Pro Asp Val Lys Arg Lys Val Asp Thr Phe Arg Ser Lys
340 345 350
Phe Tyr Ala Ile Leu Asp Phe Ile Ile Tyr Glu Ala Ser Val Ser Val
355 360 365
Ala Asn Ser Gly Gln Met Gly Lys Val Ala Pro Trp Lys Gly Ala Ile
370 375 380
Asp Asn Ala Leu Val Lys Leu Arg Glu Ala Pro Asp Glu Glu Ala Lys
385 390 395 400
Glu Lys Ile Tyr Asn Val Leu Ala Ala Ser Ile Arg Asn Asp Ser Leu
405 410 415
Phe Leu Arg Leu Lys Ser Ala Cys Asp Lys Phe Gly Ala Glu Gln Asn
420 425 430
Arg Pro Val Phe Pro Asn Glu Leu Arg Asn Asn Arg Asp Ile Arg Asn
435 440 445
Val Arg Ser Glu Trp Leu Glu Ala Thr Gln Asp Val Asp Ala Ala Ala
450 455 460
Phe Val Gln Leu Ile Ala Phe Leu Cys Asn Phe Leu Glu Gly Lys Glu
465 470 475 480
Ile Asn Glu Leu Val Thr Ala Leu Ile Lys Lys Phe Glu Gly Ile Gln
485 490 495
Ala Leu Ile Asp Leu Leu Arg Asn Leu Glu Gly Val Asp Ser Ile Arg
500 505 510
Phe Glu Asn Glu Phe Ala Leu Phe Asn Asp Asp Lys Gly Asn Met Ala
515 520 525
Gly Arg Ile Ala Arg Gln Leu Arg Leu Leu Ala Ser Val Gly Lys Met
530 535 540
Lys Pro Asp Met Thr Asp Ala Lys Arg Val Leu Tyr Lys Ser Ala Leu
545 550 555 560
Glu Ile Leu Gly Ala Pro Pro Asp Glu Val Ser Asp Glu Trp Leu Ala
565 570 575
Glu Asn Ile Leu Leu Asp Lys Ser Asn Asn Asp Tyr Gln Lys Ala Lys
580 585 590
Lys Thr Val Asn Pro Phe Arg Asn Tyr Ile Ala Lys Asn Val Ile Thr
595 600 605
Ser Arg Ser Phe Tyr Tyr Leu Val Arg Tyr Ala Lys Pro Thr Ala Val
610 615 620
Arg Lys Leu Met Ser Asn Pro Lys Ile Val Arg Tyr Val Leu Lys Arg
625 630 635 640
Leu Pro Glu Lys Gln Val Ala Ser Tyr Tyr Ser Ala Ile Trp Thr Gln
645 650 655
Ser Glu Ser Asn Ser Asn Glu Met Val Lys Leu Ile Glu Met Ile Asp
660 665 670
Arg Leu Thr Thr Glu Ile Ala Gly Phe Ser Phe Ala Val Leu Lys Asp
675 680 685
Lys Lys Asp Ser Ile Val Ser Ala Ser Arg Glu Ser Arg Ala Val Asn
690 695 700
Leu Glu Val Glu Arg Leu Lys Lys Leu Thr Thr Leu Tyr Met Ser Ile
705 710 715 720
Ala Tyr Ile Ala Val Lys Ser Leu Val Lys Val Asn Ala Arg Tyr Phe
725 730 735
Ile Ala Tyr Ser Ala Leu Glu Arg Asp Leu Tyr Phe Phe Asn Glu Lys
740 745 750
Tyr Gly Glu Glu Phe Arg Leu His Phe Ile Pro Tyr Glu Leu Asn Gly
755 760 765
Lys Thr Cys Gln Phe Glu Tyr Leu Ala Ile Leu Lys Tyr Tyr Leu Ala
770 775 780
Arg Asp Glu Glu Thr Leu Lys Arg Lys Cys Glu Ile Cys Glu Glu Ile
785 790 795 800
Lys Val Gly Cys Glu Lys His Lys Lys Asn Ala Asn Pro Pro Tyr Glu
805 810 815
Tyr Asp Gln Glu Trp Ile Asp Lys Lys Lys Ala Leu Asn Ser Glu Arg
820 825 830
Lys Ala Cys Glu Arg Arg Leu His Phe Ser Thr His Trp Ala Gln Tyr
835 840 845
Ala Thr Lys Arg Asp Glu Asn Met Ala Lys His Pro Gln Lys Trp Tyr
850 855 860
Asp Ile Leu Ala Ser His Tyr Asp Glu Leu Leu Ala Leu Gln Ala Thr
865 870 875 880
Gly Trp Leu Ala Thr Gln Ala Arg Asn Asp Ala Glu His Leu Asn Pro
885 890 895
Val Asn Glu Phe Asp Val Tyr Ile Glu Asp Leu Arg Arg Tyr Pro Glu
900 905 910
Gly Thr Pro Lys Asn Lys Asp Tyr His Ile Gly Ser Tyr Phe Glu Ile
915 920 925
Tyr His Tyr Ile Arg Gln Arg Ala Tyr Leu Glu Glu Val Leu Ala Lys
930 935 940
Arg Lys Glu Tyr Arg Asp Ser Gly Ser Phe Thr Asp Glu Gln Leu Asp
945 950 955 960
Lys Leu Gln Lys Ile Leu Asp Asp Ile Arg Ala Arg Gly Ser Tyr Asp
965 970 975
Lys Asn Leu Leu Lys Leu Glu Tyr Leu Pro Phe Ala Tyr Asn Leu Pro
980 985 990
Arg Tyr Lys Asn Leu Thr Thr Glu Ala Leu Phe Asp Asp Asp Ser Val
995 1000 1005
Ser Gly Lys Lys Arg Val Ala Glu Trp Arg Glu Arg Glu Lys Thr
1010 1015 1020
Arg Glu Ala Glu Arg Glu Gln Arg Arg Gln Arg
1025 1030
<210> 108
<211> 30
<212> DNA
<213> 未知的
<220>
<223> CasRX/Cas13d同向重复1
<400> 108
gtgagaagtc tccttatggg gagatgctac 30
<210> 109
<211> 973
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d Ga0129306 1000735
<400> 109
Met Gln Lys Gln Arg Glu Gln Gln Thr Val Thr Asp Glu Ser Glu Arg
1 5 10 15
Lys Lys Lys Pro Leu Lys Ser Gly Ala Lys Ala Ala Gly Leu Lys Ser
20 25 30
Val Phe Val Leu Ser Glu Gly Lys Glu Leu Leu Thr Ser Phe Gly Arg
35 40 45
Gly Asn Glu Ala Val Pro Glu Lys Arg Val Thr Gly Gly Thr Ile Ala
50 55 60
Asn Ala Arg Thr Asp Asn Lys Glu Ala Phe Ser Ala Ala Leu Gln Asn
65 70 75 80
Lys Arg Phe Glu Val Phe Gly Arg Thr Ala Gly Ser Ser Asp Asp Pro
85 90 95
Leu Ala Val Ser Arg Ala Pro Gly Gln Asp Leu Ile Gly Ala Lys Thr
100 105 110
Ala Leu Glu Glu Arg Tyr Phe Gly Arg Ala Phe Ala Asp Asn Ile His
115 120 125
Met Gln Val Ile Tyr Ala Ile Gln Asp Ile Asn Lys Ile Leu Ala Val
130 135 140
His Ala Asn Asn Ile Val Tyr Thr Leu Asn Asn Leu Asp Arg Glu Ala
145 150 155 160
Asp Pro Glu Thr Asp Asp Phe Ile Gly Ser Gly Tyr Leu Thr Leu Lys
165 170 175
Asn Thr Phe Glu Thr Tyr Cys Asp Pro Ala Ala Leu Asn Glu Arg Glu
180 185 190
Arg Glu Lys Val Thr Val Ser Lys Gln His Phe Asp Ala Phe Met Gln
195 200 205
Asn Pro Arg Leu Ala Tyr Tyr Gly Asn Ala Phe Phe Arg Lys Leu Ser
210 215 220
Lys Ala Glu Arg Leu Ala Arg Gly Arg Glu Ile Phe Asp Lys Glu Ser
225 230 235 240
Pro Glu Arg Arg Gln Glu Ile Leu Gly Ser Arg Gly Lys Asn Lys Ser
245 250 255
Val Asp Asp Glu Ile Arg Ala Leu Ala Pro Glu Trp Val Lys Arg Glu
260 265 270
Glu Arg Asp Val Tyr Ser Glu Leu Val Leu Met Ser Glu Leu Arg Gln
275 280 285
Ser Cys Phe His Gly Gln Gln Lys Asn Ser Ala Arg Ile Phe Arg Leu
290 295 300
Asp Asn Asp Leu Gly Pro Gly Val Asp Gly Ala Arg Glu Leu Leu Asp
305 310 315 320
Arg Leu Tyr Ala Glu Lys Ile Asn Asp Leu Arg Ser Phe Asp Lys Thr
325 330 335
Ser Ala Ser Ser Asn Phe Arg Leu Leu Phe Asn Ala Tyr His Ala Asp
340 345 350
Asn Glu Lys Lys Lys Glu Leu Ala Gln Glu Phe Tyr Arg Phe Ser Val
355 360 365
Leu Lys Val Ser Lys Asn Thr Gly Phe Ser Ile Arg Thr Leu Arg Glu
370 375 380
Lys Ile Ile Glu Asp His Ala Ala Gln Tyr Arg Asp Lys Ile Tyr Asp
385 390 395 400
Ser Met Arg Lys Lys Leu Phe Ser Thr Phe Asp Phe Phe Leu Trp Arg
405 410 415
Phe Tyr Glu Glu Arg Glu Asp Glu Ala Glu Glu Leu Arg Ala Cys Leu
420 425 430
Arg Ala Ala Arg Ser Asp Glu Glu Lys Glu Gln Ile Tyr Ala Glu Ala
435 440 445
Ala Ala Ser Cys Trp Pro Ser Val Lys Pro Phe Val Glu Ser Val Ala
450 455 460
Ala Thr Leu Cys Asp Val Val Lys Gly Arg Thr Lys Leu Asn Lys Leu
465 470 475 480
Lys Leu Ser Ala Asp Glu Ser Thr Leu Val Arg Asn Ala Ile Asp Gly
485 490 495
Val Arg Ile Ser Pro Arg Ala Ser Tyr Phe Thr Lys Leu Ile Tyr Leu
500 505 510
Met Thr Leu Phe Leu Asp Gly Lys Glu Ile Asn Asp Leu Leu Thr Thr
515 520 525
Leu Ile His Ala Phe Glu Asn Ile Asp Ser Phe Leu Ser Val Leu Gly
530 535 540
Ser Glu Arg Leu Glu Arg Thr Phe Asp Ala Asn Tyr Arg Ile Phe Ala
545 550 555 560
Asp Ser Gly Val Ile Ala Gln Glu Leu Arg Ala Val Asn Ser Phe Ala
565 570 575
Arg Met Thr Thr Glu Pro Phe Asn Ser Lys Leu Val Met Phe Glu Asp
580 585 590
Ala Ala Gln Leu Phe Gly Met Ser Gly Gly Leu Val Glu His Ala Glu
595 600 605
Glu Leu Arg Glu Tyr Leu Asp Asn Lys Met Leu Asp Lys Thr Lys Leu
610 615 620
Arg Leu Leu Pro Asp Gly Lys Val Asp Thr Gly Phe Arg Asn Phe Ile
625 630 635 640
Ile Ser Asn Val Thr Glu Ser Arg Arg Phe Arg Tyr Leu Val Arg Tyr
645 650 655
Cys Glu Pro Arg Ala Val Arg Asp Tyr Met Ser Cys Arg Pro Leu Ile
660 665 670
Arg Leu Thr Leu Arg Asp Met Pro Asp Thr Ile Leu Arg Arg Tyr Tyr
675 680 685
Glu Gln Ser Val Gly Ala Ala Thr Val Asp Arg Glu Arg Ile Leu Asp
690 695 700
Thr Leu Ala Asp Lys Leu Leu Ser Leu Arg Phe Thr Asp Phe Glu Asn
705 710 715 720
Val Asn Gln Arg Ala Asn Ala Glu Arg Asn Arg Glu Lys Gln Lys Met
725 730 735
Met Gly Ile Ile Ser Leu Tyr Leu Asn Val Ala Tyr Gln Ile Val Lys
740 745 750
Asn Leu Val Tyr Val Asn Ala Arg Tyr Thr Met Ala Tyr His Cys Ala
755 760 765
Glu Arg Asp Thr Glu Leu Leu Leu Asn Ala Ala Gly Glu Gly Asn Leu
770 775 780
Leu Arg Arg Asp Arg Ser Trp Pro Ala Arg Leu His Leu Pro Arg Arg
785 790 795 800
Ala Leu Ala Arg Arg Arg Asp Arg Val Glu Val Met Glu Arg Asp Val
805 810 815
Ala Arg Gly Pro Glu Ala Tyr Asn Arg Asp Glu Trp Leu Gly Leu Val
820 825 830
Arg Thr Leu Arg Arg Glu Lys Arg Val Cys Asp Asn Leu His Asn Asn
835 840 845
Tyr Ala Tyr Leu Cys Gly Ala Asp Ala Glu Pro Gly Asp Ala Ser Leu
850 855 860
Ser Leu Leu Phe Val Tyr Arg Asn Lys Ala Ala His Leu Ser Val Leu
865 870 875 880
Asn Lys Gly Gly Arg Leu Ser Gly Asp Leu Lys Glu Ala Lys Ser Trp
885 890 895
Phe Tyr Val Tyr His Phe Leu Met Gln Arg Val Leu Glu Glu Glu Phe
900 905 910
Arg Asn Thr Gln Ala Leu Pro Glu Arg Leu Arg Glu Leu Leu Met Met
915 920 925
Ala Glu Arg Tyr Arg Gly Cys Ser Lys Asp Leu Ile Lys Val Leu Asn
930 935 940
Leu Thr Phe Ala Tyr Asn Leu Pro Arg Tyr Lys Asn Leu Ser Ile Asp
945 950 955 960
Gly Arg Phe Asp Lys Asn His Pro Asp Pro Ser Asp Glu
965 970
<210> 110
<211> 854
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d Ga0129317 1008067
<400> 110
Met Lys Lys Gln Lys Lys Ser Leu Val Lys Ala Ala Gly Leu Lys Ser
1 5 10 15
Ala Phe Val Val Gly Asp Ser Val Tyr Leu Thr Ser Phe Gly Lys Gly
20 25 30
Asn Ala Ala Arg Leu Asp Thr Lys Ile Asn Pro Asp Asn Ser Thr Glu
35 40 45
Arg Tyr Val Ser Asp Ser Glu Lys His Thr Leu Lys Ile Asn Ser Ile
50 55 60
Thr Asp Thr Glu Leu Arg Leu Ser Gly Pro Phe Pro Lys Gln Ala Glu
65 70 75 80
Ala Lys Asn Pro Thr His Lys Lys Asp Asn Glu Gln Lys Asn Thr Arg
85 90 95
Gln Asp Met Leu Gly Leu Lys Ser Thr Leu Glu Lys Phe Tyr Phe Gly
100 105 110
Ser Thr Phe Asp Asp Asn Ile His Ile Gln Ile Ile His Asn Ile Gln
115 120 125
Asp Ile Ala Lys Ile Leu Ala Ala His Ser Asn Asn Ala Gly Tyr Ala
130 135 140
Leu Asp Asn Met Leu Ala Tyr Gln Gly Val Glu Phe Ser Asp Met Ile
145 150 155 160
Gly Tyr Met Gly Thr Ser Arg Thr Phe Asp Asn Tyr Asp Pro Asn His
165 170 175
Lys Asn Asn Lys Asp Phe Phe Arg Phe Leu Lys Leu Pro Arg Leu Gly
180 185 190
Tyr Phe Gly Ser Ala Phe Tyr Ser Gln Lys Gly Lys Asp Phe Glu Lys
195 200 205
Arg Ser Asp Glu Glu Val Tyr Asn Ile Cys Ala Leu Met Gly Gln Ile
210 215 220
Arg Gln Cys Cys Phe His Gly Lys Gln Glu Lys Tyr Gln Leu Lys Trp
225 230 235 240
Leu Tyr Asn Phe His Asn Phe Lys Ser Asn Lys Pro Phe Leu Asp Thr
245 250 255
Leu Asp Lys His Phe Asp Glu Met Ile Asp Arg Ile Asn Lys Asn Phe
260 265 270
Ile Lys Asn Asn Thr Pro Asp Leu Ile Ile Leu Ser Gly Leu Tyr Pro
275 280 285
Asp Met Ala Lys Lys Glu Leu Val Arg Leu Phe Tyr Asp Phe Thr Thr
290 295 300
Val Lys Glu Tyr Lys Asn Met Gly Phe Ser Val Lys Lys Leu Arg Glu
305 310 315 320
Lys Met Leu Glu Ser Glu Glu Ala Ser Asp Phe Arg Asp Lys Asp Tyr
325 330 335
Asp Ser Val Arg Arg Lys Leu Tyr Lys Leu Met Asp Phe Cys Ile Tyr
340 345 350
Tyr Leu Tyr Tyr Ser Asp Ser Glu Arg Asn Glu Asn Leu Val Ser Arg
355 360 365
Leu Arg Glu Ser Leu Thr Asp Glu Asn Lys Asp Ile Ile Tyr Ser Lys
370 375 380
Glu Ala Lys Ile Val Trp Asn Glu Leu Arg Lys Lys Phe Ser Thr Ile
385 390 395 400
Leu Asp Asn Val Lys Gly Ser Asn Ile Lys Lys Leu Glu Asn Val Lys
405 410 415
Glu Lys Phe Ile Ser Glu Asp Glu Phe Asp Asp Ile Lys Leu Asp Ile
420 425 430
Asp Ile Ser Tyr Phe Ser Lys Leu Met Tyr Val Met Cys Tyr Phe Leu
435 440 445
Asp Gly Lys Glu Ile Asn Asp Leu Leu Thr Thr Leu Val Ser Lys Phe
450 455 460
Asp Asn Ile Gly Ser Ile Ile Glu Ala Ala Thr Gln Ile Gly Ile Asn
465 470 475 480
Ile Glu Phe Ile Asp Asp Phe Lys Phe Phe Asp Arg Ser Lys Asp Ile
485 490 495
Ser Val Glu Leu Asn Ile Ile Arg Asn Phe Ala Arg Met Gln Ala Pro
500 505 510
Val Pro Asn Ala Lys Arg Ala Met Gln Glu Asp Ala Ile Arg Ile Leu
515 520 525
Gly Gly Ser Glu Glu Asp Ile Phe Ser Ile Leu Asp Asp Met Thr Gly
530 535 540
Tyr Asp Lys Ser Gly Lys Lys Leu Ala Gln Ser Lys Lys Gly Phe Arg
545 550 555 560
Asn Phe Ile Ile Asn Asn Val Val Glu Ser Ser Arg Phe Lys Tyr Ile
565 570 575
Val Arg Tyr Ser Asn Pro Gln Lys Ile Arg Lys Leu Ala Asn Asn Ser
580 585 590
Val Val Val Gly Phe Val Leu Gly Lys Leu Pro Asp Ala Gln Ile Glu
595 600 605
Ser Tyr Phe Asn Ser Cys Leu Pro Asn Arg Val Tyr Ser Thr Pro Asp
610 615 620
Lys Ala Arg Glu Ser Leu Arg Asp Met Leu His Asn Ile Ser Phe Asn
625 630 635 640
Asp Phe Ala Asp Val Lys Gln Asp Asp Arg Arg Ala Thr Pro Glu Glu
645 650 655
Lys Val Glu Lys Glu Arg Tyr Lys Ala Ile Ile Gly Leu Tyr Leu Thr
660 665 670
Val Met Tyr His Leu Val Lys Asn Leu Val Tyr Val Asn Ser Arg Tyr
675 680 685
Val Met Ala Phe His Cys Leu Glu Arg Asp Ala Met His Tyr Asp Val
690 695 700
Ser Leu Asp Asn Tyr Arg Asp Leu Ile Arg His Leu Ile Ser Glu Gly
705 710 715 720
Asp Ser Ser Cys Asn His Phe Ile Ser His Asn Arg Arg Met Arg Asp
725 730 735
Cys Ile Glu Glu Asn Val Lys Asn Ser Glu Gln Leu Ile Phe Gly Lys
740 745 750
Glu Asp Ala Val Ile Arg Phe Arg Asn Asn Val Ala His Leu Ser Ala
755 760 765
Ile Arg Asn Ala Asn Glu Tyr Ile Gly Asp Ile Arg Glu Ile Thr Ser
770 775 780
Tyr Phe Ala Leu Tyr His Tyr Leu Met Gln Arg Lys Leu Ile Asp Asp
785 790 795 800
Cys Lys Val Asn Asp Thr Ala His Lys Tyr Phe Glu Gln Leu Thr Lys
805 810 815
Tyr Lys Thr Tyr Val Met Asp Met Val Lys Ala Leu Cys Ser Pro Phe
820 825 830
Gly Tyr Asn Leu Pro Arg Phe Lys Asn Leu Ser Ile Glu Gly Lys Phe
835 840 845
Asp Met His Glu Ser Lys
850
<210> 111
<211> 965
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d Ga0224415 10048792
<400> 111
Met Ser Lys Lys Glu Asn Arg Lys Ser Tyr Val Lys Gly Leu Gly Leu
1 5 10 15
Lys Ser Thr Leu Val Ser Asp Ser Lys Val Tyr Leu Thr Thr Phe Ala
20 25 30
Asp Gly Ser Asn Ala Lys Leu Glu Lys Cys Val Glu Asn Asn Lys Ile
35 40 45
Ile Cys Ile Ser Asn Asp Lys Glu Ala Phe Ala Ala Ser Ile Ala Asn
50 55 60
Lys Asn Val Gly Tyr Lys Ile Lys Asn Asp Glu Lys Phe Arg His Pro
65 70 75 80
Lys Gly Tyr Asp Ile Ile Ser Asn Asn Pro Leu Leu His Asn Asn Ser
85 90 95
Val Gln Gln Asp Met Leu Gly Leu Lys Asn Val Leu Glu Lys Arg Tyr
100 105 110
Phe Gly Lys Ser Ser Gly Gly Asp Asn Asn Leu Cys Ile Gln Ile Ile
115 120 125
His Asn Ile Ile Asp Ile Glu Lys Ile Leu Ser Glu Tyr Ile Pro Asn
130 135 140
Val Val Tyr Ala Phe Asn Asn Ile Ala Gly Phe Lys Asp Glu His Asn
145 150 155 160
Asn Ile Ile Asp Ile Ile Gly Thr Gln Thr Tyr Asn Ser Ser Tyr Thr
165 170 175
Tyr Ala Asp Phe Ser Lys Asp Lys Ser Asp Lys Lys Tyr Ile Glu Phe
180 185 190
Gln Lys Leu Leu Lys Asn Lys Arg Leu Gly Tyr Trp Gly Lys Ala Phe
195 200 205
Phe Thr Gly Gln Gly Asn Asn Ala Lys Val Arg Gln Glu Asn Gln Cys
210 215 220
Phe His Ile Ile Ala Leu Leu Ile Ser Leu Arg Asn Trp Ala Thr His
225 230 235 240
Ser Asn Glu Leu Asp Lys His Thr Lys Arg Thr Trp Leu Tyr Lys Leu
245 250 255
Asp Asp Thr Asn Ile Leu Asn Ala Glu Tyr Val Lys Thr Leu Asn Tyr
260 265 270
Leu Tyr Asp Thr Ile Ala Asp Glu Leu Thr Lys Ser Phe Ser Lys Asn
275 280 285
Gly Ala Val Asn Val Asn Tyr Leu Ala Lys Lys Tyr Asn Ile Lys Asp
290 295 300
Asp Leu Pro Gly Phe Ser Glu Gln Tyr Phe Arg Phe Ser Ile Met Lys
305 310 315 320
Glu Gln Lys Asn Leu Gly Phe Asn Ile Ser Lys Leu Arg Glu Asn Met
325 330 335
Leu Asp Phe Lys Asp Met Ser Val Ile Arg Asp Asp His Asn Arg Tyr
340 345 350
Asp Lys Asp Arg Ser Lys Ile Tyr Thr Met Met Asp Phe Val Ile Tyr
355 360 365
Arg Tyr Tyr Ile Asp Asn Asn Asn Asp Ser Ile Asp Phe Ile Asn Lys
370 375 380
Leu Arg Ser Ser Ile Asp Glu Lys Ser Lys Glu Lys Leu Tyr Asn Glu
385 390 395 400
Glu Ala Asn Arg Leu Trp Asn Lys Leu Lys Glu Tyr Met Leu Tyr Ile
405 410 415
Lys Glu Phe Asn Gly Lys Leu Ala Ser Arg Thr Pro Asp Arg Asp Gly
420 425 430
Asn Ile Ser Glu Phe Val Glu Ser Leu Pro Lys Ile His Arg Leu Leu
435 440 445
Pro Arg Gly Gln Lys Ile Ser Asn Phe Ser Lys Leu Met Tyr Leu Leu
450 455 460
Thr Met Phe Leu Asp Gly Lys Glu Ile Asn Asp Leu Leu Thr Thr Leu
465 470 475 480
Ile Asn Lys Phe Glu Asn Ile Gln Gly Phe Leu Asp Ile Met Pro Glu
485 490 495
Ile Asn Val Asn Ala Lys Phe Glu Pro Glu Tyr Val Phe Phe Asn Lys
500 505 510
Ser His Glu Ile Ala Gly Glu Leu Lys Leu Ile Lys Gly Phe Ala Gln
515 520 525
Met Gly Glu Pro Ala Ala Thr Leu Lys Leu Glu Met Thr Ala Asp Ala
530 535 540
Ile Lys Ile Leu Gly Thr Glu Lys Glu Asp Ala Glu Leu Ile Lys Leu
545 550 555 560
Ala Glu Ser Leu Phe Lys Asp Glu Asn Gly Lys Leu Leu Gly Asn Lys
565 570 575
Gln His Gly Met Arg Asn Phe Ile Gly Asn Asn Val Ile Lys Ser Lys
580 585 590
Arg Phe His Tyr Leu Ile Arg Tyr Gly Asp Pro Ala His Leu His Lys
595 600 605
Ile Ala Thr Asn Lys Asn Val Val Arg Phe Val Leu Gly Arg Ile Ala
610 615 620
Asp Met Gln Lys Lys Gln Gly Gln Lys Gly Lys Asn Gln Ile Asp Arg
625 630 635 640
Tyr Tyr Glu Val Cys Val Gly Asn Lys Asp Ile Lys Lys Thr Ile Glu
645 650 655
Glu Lys Ile Asp Ala Leu Thr Asp Ile Ile Val Asn Met Asn Tyr Asp
660 665 670
Gln Phe Glu Lys Lys Lys Ala Val Ile Glu Asn Gln Asn Arg Gly Lys
675 680 685
Thr Phe Glu Glu Lys Asn Lys Tyr Lys Arg Asp Asn Ala Glu Arg Glu
690 695 700
Lys Phe Lys Lys Ile Ile Ser Leu Tyr Leu Thr Val Ile Tyr His Ile
705 710 715 720
Leu Lys Asn Ile Val Asn Val Asn Ser Arg Tyr Ile Leu Gly Phe His
725 730 735
Cys Leu Glu Arg Asp Lys Gln Leu Tyr Ile Glu Lys Tyr Asn Lys Asp
740 745 750
Lys Leu Asp Gly Phe Val Ala Leu Thr Lys Phe Cys Leu Gly Asp Glu
755 760 765
Glu Arg Phe Glu Asp Leu Lys Ala Lys Ala Gln Ala Ser Ile Gln Ala
770 775 780
Leu Glu Thr Ala Asn Pro Lys Leu Tyr Ala Lys Tyr Met Asn Tyr Ser
785 790 795 800
Asp Glu Glu Lys Lys Glu Glu Phe Lys Lys Gln Leu Asn Arg Glu Arg
805 810 815
Val Lys Asn Ala Arg Asn Ala Tyr Leu Lys Asn Ile Lys Asn Tyr Ile
820 825 830
Met Ile Arg Leu Gln Leu Arg Asp Gln Thr Asp Ser Ser Gly Tyr Leu
835 840 845
Cys Gly Glu Phe Arg Asp Lys Val Ala His Leu Glu Val Ala Arg His
850 855 860
Ala His Glu Tyr Ile Gly Asn Ile Lys Glu Val Asn Ser Tyr Phe Gln
865 870 875 880
Leu Tyr His Tyr Ile Met Gln Cys Arg Leu Tyr Asp Val Leu Lys Asn
885 890 895
Asn Thr Lys Ala Glu Ala Met Val Lys Gly Lys Ala Lys Glu Tyr Phe
900 905 910
Glu Ala Leu Glu Lys Glu Gly Thr Tyr Asn Asp Lys Leu Leu Lys Ile
915 920 925
Ala Cys Val Pro Phe Gly Tyr Cys Ile Pro Arg Tyr Lys Asn Leu Ser
930 935 940
Met Glu Glu Leu Phe Asp Met Asn Glu Glu Lys Lys Phe Lys Lys Lys
945 950 955 960
Ala Pro Glu Asn Thr
965
<210> 112
<211> 1022
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d 160582958 基因49834
<400> 112
Met Lys Asn Ser Val Thr Phe Lys Leu Ile Gln Ala Gln Glu Asn Lys
1 5 10 15
Glu Ala Ala Arg Lys Lys Ala Lys Asp Ile Ala Glu Gln Ala Arg Ile
20 25 30
Ala Lys Arg Asn Gly Val Val Lys Lys Glu Glu Asn Arg Ile Asn Arg
35 40 45
Ile Gln Ile Glu Ile Gln Thr Gln Lys Lys Ser Asn Thr Gln Asn Ala
50 55 60
Tyr His Leu Lys Ser Leu Ala Lys Ala Ala Gly Val Lys Ser Val Phe
65 70 75 80
Ala Ile Gly Asn Asp Leu Leu Met Thr Gly Phe Gly Pro Gly Asn Asp
85 90 95
Ala Thr Ile Glu Lys Arg Val Phe Gln Asn Arg Ala Ile Glu Thr Leu
100 105 110
Ser Ser Pro Glu Gln Tyr Ser Ala Glu Phe Gln Asn Lys Gln Phe Lys
115 120 125
Ile Lys Gly Asn Ile Lys Val Leu Asn His Ser Thr Gln Lys Met Glu
130 135 140
Glu Ile Gln Thr Glu Leu Gln Asp Asn Tyr Asn Arg Pro His Phe Asp
145 150 155 160
Leu Leu Gly Cys Lys Asn Val Leu Glu Gln Lys Tyr Phe Gly Arg Thr
165 170 175
Phe Ser Asp Asn Ile His Val Gln Ile Ala Tyr Asn Ile Met Asp Ile
180 185 190
Glu Lys Leu Leu Thr Pro Tyr Ile Asn Asn Ile Ile Tyr Thr Leu Asn
195 200 205
Glu Leu Met Arg Asp Asn Ser Lys Asp Asp Phe Phe Gly Cys Asp Ser
210 215 220
His Phe Ser Val Ala Tyr Leu Tyr Asp Glu Leu Lys Ala Gly Tyr Ser
225 230 235 240
Asp Arg Leu Lys Thr Lys Pro Asn Leu Ser Lys Asn Ile Asp Arg Ile
245 250 255
Trp Asn Asn Phe Cys Asn Tyr Met Asn Ser Asp Ser Gly Asn Thr Glu
260 265 270
Ala Arg Leu Ala Tyr Phe Gly Glu Leu Phe Tyr Lys Pro Lys Glu Thr
275 280 285
Gly Asp Ala Lys Ser Asp Tyr Lys Thr His Leu Ser Asn Asn Gln Lys
290 295 300
Glu Glu Trp Glu Leu Lys Ser Asp Lys Glu Val Tyr Asn Ile Phe Ala
305 310 315 320
Ile Leu Cys Asp Leu Arg His Phe Cys Thr His Gly Glu Ser Ile Thr
325 330 335
Pro Ser Gly Lys Pro Phe Pro Tyr Asn Leu Glu Lys Asn Leu Phe Pro
340 345 350
Glu Ala Lys Gln Val Leu Asn Ser Leu Phe Glu Glu Lys Ala Glu Ser
355 360 365
Leu Gly Ala Glu Ala Phe Gly Lys Thr Ala Gly Lys Thr Asp Val Ser
370 375 380
Ile Leu Leu Lys Val Phe Glu Lys Glu Gln Ala Ser Gln Lys Glu Gln
385 390 395 400
Gln Ala Leu Leu Lys Glu Tyr Tyr Asp Phe Lys Val Gln Lys Thr Tyr
405 410 415
Lys Asn Met Gly Phe Ser Ile Lys Lys Leu Arg Glu Ala Ile Met Glu
420 425 430
Ile Pro Asp Ala Ala Lys Phe Lys Asp Asp Leu Tyr Ser Ser Leu Arg
435 440 445
His Lys Leu Tyr Gly Leu Phe Asp Phe Ile Leu Val Lys His Phe Leu
450 455 460
Asp Thr Ser Asp Ser Glu Asn Leu Gln Asn Asn Asp Ile Phe Arg Gln
465 470 475 480
Leu Arg Ala Cys Arg Cys Glu Glu Glu Lys Asp Gln Val Tyr Arg Ser
485 490 495
Ile Ala Val Lys Val Trp Glu Lys Val Lys Lys Lys Glu Leu Asn Met
500 505 510
Phe Lys Gln Val Val Val Ile Pro Ser Leu Ser Lys Asp Glu Leu Lys
515 520 525
Gln Met Glu Met Thr Lys Asn Thr Glu Leu Leu Ser Ser Ile Glu Thr
530 535 540
Ile Ser Thr Gln Ala Ser Leu Phe Ser Glu Met Ile Phe Met Met Thr
545 550 555 560
Tyr Leu Leu Asp Gly Lys Glu Ile Asn Leu Leu Cys Thr Ser Leu Ile
565 570 575
Glu Lys Phe Glu Asn Ile Ala Ser Phe Asn Glu Val Leu Lys Ser Pro
580 585 590
Gln Ile Gly Tyr Glu Thr Lys Tyr Thr Glu Gly Tyr Ala Phe Phe Lys
595 600 605
Asn Ala Asp Lys Thr Ala Lys Glu Leu Arg Gln Val Asn Asn Met Ala
610 615 620
Arg Met Thr Lys Pro Leu Gly Gly Val Asn Thr Lys Cys Val Met Tyr
625 630 635 640
Asn Glu Ala Ala Lys Ile Leu Gly Ala Lys Pro Met Ser Lys Ala Glu
645 650 655
Leu Glu Ser Val Phe Asn Leu Asp Asn His Asp Tyr Thr Tyr Ser Pro
660 665 670
Ser Gly Lys Lys Ile Pro Asn Lys Asn Phe Arg Asn Phe Ile Ile Asn
675 680 685
Asn Val Ile Thr Ser Arg Arg Phe Leu Tyr Leu Ile Arg Tyr Gly Asn
690 695 700
Pro Glu Lys Ile Arg Lys Ile Ala Ile Asn Pro Ser Ile Ile Ser Phe
705 710 715 720
Val Leu Lys Gln Ile Pro Asp Glu Gln Ile Lys Arg Tyr Tyr Pro Pro
725 730 735
Cys Ile Gly Lys Arg Thr Asp Asp Val Thr Leu Met Arg Asp Glu Leu
740 745 750
Gly Lys Met Leu Gln Ser Val Asn Phe Glu Gln Phe Ser Arg Val Asn
755 760 765
Asn Lys Gln Asn Ala Lys Gln Asn Pro Asn Gly Glu Lys Ala Arg Leu
770 775 780
Gln Ala Cys Val Arg Leu Tyr Leu Thr Val Pro Tyr Leu Phe Ile Lys
785 790 795 800
Asn Met Val Asn Ile Asn Ala Arg Tyr Val Leu Ala Phe His Cys Leu
805 810 815
Glu Arg Asp His Ala Leu Cys Phe Asn Ser Arg Lys Leu Asn Asp Asp
820 825 830
Ser Tyr Asn Glu Met Ala Asn Lys Phe Gln Met Val Arg Lys Ala Lys
835 840 845
Lys Glu Gln Tyr Glu Lys Glu Tyr Lys Cys Lys Lys Gln Glu Thr Gly
850 855 860
Thr Ala His Thr Lys Lys Ile Glu Lys Leu Asn Gln Gln Ile Ala Tyr
865 870 875 880
Ile Asp Lys Asp Ile Lys Asn Met His Ser Tyr Thr Cys Arg Asn Tyr
885 890 895
Arg Asn Leu Val Ala His Leu Asn Val Val Ser Lys Leu Gln Asn Tyr
900 905 910
Val Ser Glu Leu Pro Asn Asp Tyr Gln Ile Thr Ser Tyr Phe Ser Phe
915 920 925
Tyr His Tyr Cys Met Gln Leu Gly Leu Met Glu Lys Val Ser Ser Lys
930 935 940
Asn Ile Pro Leu Val Glu Ser Leu Lys Asn Glu Ala Asn Asp Ala Gln
945 950 955 960
Ser Tyr Ser Ala Lys Lys Thr Leu Glu Tyr Phe Asp Leu Ile Glu Lys
965 970 975
Asn Arg Thr Tyr Cys Lys Asp Phe Leu Lys Ala Leu Asn Ala Pro Phe
980 985 990
Ser Tyr Asn Leu Pro Arg Phe Lys Asn Leu Ser Ile Glu Ala Leu Phe
995 1000 1005
Asp Lys Asn Ile Val Tyr Glu Gln Ala Asp Leu Lys Lys Glu
1010 1015 1020
<210> 113
<211> 36
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d DR
<400> 113
Gly Ala Ala Cys Thr Ala Cys Ala Cys Cys Cys Cys Thr Cys Thr Gly
1 5 10 15
Thr Thr Cys Thr Thr Gly Thr Ala Gly Gly Gly Gly Thr Cys Thr Ala
20 25 30
Ala Cys Ala Cys
35
<210> 114
<211> 998
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d 250twins 35838 GL0110300
<400> 114
Met Gly Asn Lys Gln Arg Val Ser Ala Gln Lys Arg Arg Glu Asn Ala
1 5 10 15
Lys Leu Cys Asn Gln Gln Lys Ala Arg Gln Ala Glu Ser Gln Arg Asp
20 25 30
Lys Ile Lys Asn Met Asn Val Glu Lys Met Lys Asn Ile Asn Thr Asn
35 40 45
Asp Ile Lys His Thr Lys Thr Thr Ala Lys Lys Leu Gly Leu Lys Ser
50 55 60
Thr Ile Ile Ala Asp Lys Lys Ile Ile Leu Thr Ser Phe Ile Asn Glu
65 70 75 80
Gln Ser Ser Lys Thr Ala Asn Ile Glu Lys Val Ala Gly Phe Lys Gly
85 90 95
Asp Thr Ile Asp Thr Ile Ser Tyr Thr Pro Arg Met Phe Arg Ser Glu
100 105 110
Ile Asn Pro Gly Glu Ile Val Ile Ser Lys Gly Asp Asp Leu Ser Glu
115 120 125
Phe Ala Asn Pro Ala Asn Phe Pro Ile Gly Arg Asp Tyr Val Lys Ile
130 135 140
Arg Ser Ala Leu Glu Lys Gln Tyr Phe Gly Lys Glu Phe Pro Glu Asp
145 150 155 160
Asn Leu His Val Gln Ile Ala Tyr Asn Val Ala Asp Ile Lys Lys Ile
165 170 175
Leu Ser Val Tyr Ile Asn Asn Ile Ile Tyr Met Phe Tyr Asn Leu Ala
180 185 190
Arg Ser Glu Glu Tyr Asp Ile Phe Tyr Asn Ser Gln Ser Glu Asn Ser
195 200 205
Gly Arg Asp Cys Asp Val Ile Gly Ser Leu Tyr Tyr Gln Ala Ser Tyr
210 215 220
Arg Asn Gln Asp Ala Asn Arg Phe Glu Lys Asp Gly Lys Lys Lys Ala
225 230 235 240
Ile Asp Ser Leu Leu Asp Asp Thr Arg Ala Tyr Tyr Thr Tyr Phe Asp
245 250 255
Gly Leu Phe Ser Val Pro Lys Arg Glu Asp Asp Gly Lys Ile Lys Glu
260 265 270
Ser Glu Lys Glu Lys Ala Lys Asp Gln Asn Phe Asp Val Leu Arg Leu
275 280 285
Leu Ser Val Gly Arg Gln Leu Thr Phe His Ser Asp Lys Ser Asn Asn
290 295 300
Glu Ala Tyr Leu Phe Asp Leu Ser Lys Leu Thr Arg Ala Ala Gln Asp
305 310 315 320
Glu Asn Arg Arg Gln Asp Ile Gln Ser Leu Leu Asn Ile Leu Asn Ser
325 330 335
Thr Cys Arg Ser Asn Leu Glu Gly Val Asn Gly Asp Phe Val Lys His
340 345 350
Ala Lys Asn Asn Leu Tyr Val Leu Asn Gln Leu Tyr Pro Ser Leu Lys
355 360 365
Ala Asn Asp Leu Ile Gly Glu Tyr Tyr Asn Phe Ile Val Lys Lys Glu
370 375 380
Asn Arg Asn Ile Gly Ile Arg Leu Ile Thr Val Arg Glu Leu Ile Ile
385 390 395 400
Glu His Asn Tyr Thr Asn Leu Lys Asp Ser Lys Tyr Asp Thr Tyr Arg
405 410 415
Asn Lys Ile Tyr Thr Val Leu Asn Phe Ile Leu Phe Arg Glu Ile Gln
420 425 430
Glu Asn Ser Ile Ala Ile Lys Asn Phe Arg Glu Lys Leu Arg Ser Thr
435 440 445
Glu Lys Ala Glu Gln Pro Ala Leu Tyr Gln Ala Phe Ala Asn Lys Ile
450 455 460
Tyr Pro Met Val Gln Ala Lys Phe Ala Lys Ala Ile Asp Leu Phe Glu
465 470 475 480
Glu Gln Tyr Lys Thr Lys Phe Lys Ser Glu Phe Lys Gly Gly Ile Ser
485 490 495
Ile Glu Asn Met Gln Gln Gln Asn Ile Leu Leu Gln Thr Glu Asn Ile
500 505 510
Asp Tyr Phe Ser Lys Tyr Val Leu Phe Leu Thr Lys Phe Leu Asp Gly
515 520 525
Lys Glu Ile Asn Glu Leu Leu Cys Ala Leu Ile Asn Lys Phe Asp Asn
530 535 540
Ile Ala Asp Leu Leu Asp Ile Ser Lys Gln Ile Gly Thr Pro Val Val
545 550 555 560
Phe Cys Ala Asp Tyr Glu Ser Leu Asn Asp Ala Ala Lys Ile Ala Glu
565 570 575
Asn Ile Arg Leu Ile Lys Asn Ile Ala His Leu Arg Pro Ala Ile Gln
580 585 590
Glu Ala Gln Ser Ser Lys Asp Asn Ala Asp Ala Ala Gly Thr Pro Ala
595 600 605
Thr Leu Leu Ile Asp Ala Tyr Asn Met Leu Asn Thr Asp Ile Gln Leu
610 615 620
Val Tyr Gly Glu Ala Ala Tyr Glu Glu Leu Arg Lys Asp Leu Phe Glu
625 630 635 640
Arg Lys Asn Gly Thr Lys Tyr Asn Lys Lys Gly Lys Lys Val Asp Val
645 650 655
Tyr Asp His Lys Phe Arg Asn Phe Leu Ile Asn Asn Val Ile Lys Ser
660 665 670
Lys Trp Phe Phe Tyr Ile Ala Lys Tyr Val Lys Pro Ala Asp Cys Ala
675 680 685
Lys Met Met Ser Asn Lys Lys Met Ile Glu Phe Ala Leu Arg Asp Leu
690 695 700
Pro Glu Thr Gln Ile Lys Arg Tyr Tyr Tyr Thr Ile Thr Gly Asn Glu
705 710 715 720
Ala Leu Gly Asp Ala Glu Ser Leu Lys Gly Val Ile Ile Glu Gln Leu
725 730 735
His Ala Phe Ser Ile Lys Asn Thr Leu Leu Ser Ile Lys Asn Met Gly
740 745 750
Glu Gly Glu Tyr Lys Ile Gln Gln Ile Gly Ser Ser Lys Glu Lys Leu
755 760 765
Lys Ala Ile Val Asn Leu Tyr Leu Thr Val Ala Tyr Leu Leu Thr Lys
770 775 780
Ser Leu Val Lys Val Asn Ile Arg Phe Ser Ile Ala Phe Gly Cys Leu
785 790 795 800
Glu Arg Asp Leu Val Leu Gln Lys Lys Ser Glu Lys Lys Phe Asp Ala
805 810 815
Ile Ile Asn Glu Ile Leu Leu Glu Asp Asp Lys Ile Arg Lys Glu Cys
820 825 830
Asp Lys Glu Arg Ala Gln Ala Lys Thr Leu Pro Arg Glu Leu Ala Gln
835 840 845
Glu Arg Phe Ala Gln Ile Lys Arg Arg Glu Ser Gly Cys Tyr Phe Lys
850 855 860
Ser Tyr His Val Tyr Asp Tyr Leu Ser Lys Asn Ser Asn Glu Phe Lys
865 870 875 880
Gln Asn His Ile Asp Phe Ala Val Thr Ser Tyr Arg Asn Asn Val Glu
885 890 895
His Leu Asn Val Val His Cys Met Thr Lys Tyr Phe Ser Glu Val Lys
900 905 910
Asp Val Lys Ser Tyr Tyr Gly Val Tyr Cys Tyr Ile Met Gln Arg Met
915 920 925
Leu Cys Asp Glu Leu Ile Ile Lys Asn Gln Asp Lys Pro Asp Val Arg
930 935 940
Gln Thr Phe Glu Glu Tyr Asn Arg Leu Leu Lys Asp His Gly Thr Tyr
945 950 955 960
Ser Lys Asn Leu Met Trp Leu Leu Asn Phe Pro Phe Ala Tyr Asn Leu
965 970 975
Ala Arg Tyr Lys Asn Leu Ser Asn Glu Asp Leu Phe Asn Ala Lys Asn
980 985 990
Asn Asp Gln Lys Ser Lys
995
<210> 115
<211> 1020
<212> PRT
<213> 未知的
<220>
<223> CasRX/Cas13d 250twins 36050 GL0158985
<400> 115
Met Lys Lys Lys His Gln Ser Ala Ala Glu Lys Arg Gln Val Lys Lys
1 5 10 15
Leu Lys Asn Gln Glu Lys Ala Gln Lys Tyr Ala Ser Glu Pro Ser Pro
20 25 30
Leu Gln Ser Asp Thr Ala Gly Val Glu Cys Ser Gln Lys Lys Thr Val
35 40 45
Val Ser His Ile Ala Ser Ser Lys Thr Leu Ala Lys Ala Met Gly Leu
50 55 60
Lys Ser Thr Leu Val Met Gly Asp Lys Leu Val Ile Thr Ser Phe Ala
65 70 75 80
Ala Ser Lys Ala Val Gly Gly Ala Gly Tyr Lys Ser Ala Asn Ile Glu
85 90 95
Lys Ile Thr Asp Leu Gln Gly Arg Val Ile Glu Glu His Glu Arg Met
100 105 110
Phe Ser Ala Asp Val Gly Glu Lys Asn Ile Glu Leu Ser Lys Asn Asp
115 120 125
Cys His Thr Asn Val Asn Asn Pro Val Val Thr Asn Ile Gly Lys Asp
130 135 140
Tyr Ile Gly Leu Lys Ser Arg Leu Glu Gln Glu Phe Phe Gly Lys Thr
145 150 155 160
Phe Glu Asn Asp Asn Leu His Val Gln Leu Ala Tyr Asn Ile Leu Asp
165 170 175
Ile Lys Lys Ile Leu Gly Thr Tyr Val Asn Asn Ile Ile Tyr Ile Phe
180 185 190
Tyr Asn Leu Asn Arg Ala Gly Thr Gly Arg Asp Glu Arg Met Tyr Asp
195 200 205
Asp Leu Ile Gly Thr Leu Tyr Ala Tyr Lys Pro Met Glu Ala Gln Gln
210 215 220
Thr Tyr Leu Leu Lys Gly Asp Lys Asp Met Arg Arg Phe Glu Glu Val
225 230 235 240
Lys Gln Leu Leu Gln Asn Thr Ser Ala Tyr Tyr Val Tyr Tyr Gly Thr
245 250 255
Leu Phe Glu Lys Val Lys Ala Lys Ser Lys Lys Glu Gln Arg Ala Lys
260 265 270
Glu Ala Glu Ile Asp Ala Cys Thr Ala His Asn Tyr Asp Val Leu Arg
275 280 285
Leu Leu Ser Leu Met Arg Gln Leu Cys Met His Ser Val Ala Gly Thr
290 295 300
Ala Phe Lys Leu Ala Glu Ser Ala Leu Phe Asn Ile Glu Asp Val Leu
305 310 315 320
Ser Ala Asp Leu Lys Glu Ile Leu Asp Glu Ala Phe Ser Gly Ala Val
325 330 335
Asn Lys Leu Asn Asp Gly Phe Val Gln His Ser Gly Asn Asn Leu Tyr
340 345 350
Val Leu Gln Gln Leu Tyr Pro Asn Glu Thr Ile Glu Arg Ile Ala Glu
355 360 365
Lys Tyr Tyr Arg Leu Thr Val Arg Lys Glu Asp Leu Asn Met Gly Val
370 375 380
Asn Ile Lys Lys Leu Arg Glu Leu Ile Val Gly Gln Tyr Phe Pro Glu
385 390 395 400
Val Leu Asp Lys Glu Tyr Asp Leu Ser Lys Asn Gly Asp Ser Val Val
405 410 415
Thr Tyr Arg Ser Lys Ile Tyr Thr Val Met Asn Tyr Ile Leu Leu Tyr
420 425 430
Tyr Leu Glu Asp His Asp Ser Ser Arg Glu Ser Met Val Glu Ala Leu
435 440 445
Arg Gln Asn Arg Glu Gly Asp Glu Gly Lys Glu Glu Ile Tyr Arg Gln
450 455 460
Phe Ala Lys Lys Val Trp Asn Gly Val Ser Gly Leu Phe Gly Val Cys
465 470 475 480
Leu Asn Leu Phe Lys Thr Glu Lys Arg Asn Lys Phe Arg Ser Lys Val
485 490 495
Ala Leu Pro Asp Val Ser Gly Ala Ala Tyr Met Leu Ser Ser Glu Asn
500 505 510
Ile Asp Tyr Phe Val Lys Met Leu Phe Phe Val Cys Lys Phe Leu Asp
515 520 525
Gly Lys Glu Ile Asn Glu Leu Leu Cys Ala Leu Ile Asn Lys Phe Asp
530 535 540
Asn Ile Ala Asp Ile Leu Asp Ala Ala Ala Gln Cys Gly Ser Ser Val
545 550 555 560
Trp Phe Val Asp Ser Tyr Arg Phe Phe Glu Arg Ser Arg Arg Ile Ser
565 570 575
Ala Gln Ile Arg Ile Val Lys Asn Ile Ala Ser Lys Asp Phe Lys Lys
580 585 590
Ser Lys Lys Asp Ser Asp Glu Ser Tyr Pro Glu Gln Leu Tyr Leu Asp
595 600 605
Ala Leu Ala Leu Leu Gly Asp Val Ile Ser Lys Tyr Lys Gln Asn Arg
610 615 620
Asp Gly Ser Val Val Ile Asp Asp Gln Gly Asn Ala Val Leu Thr Glu
625 630 635 640
Gln Tyr Lys Arg Phe Arg Tyr Glu Phe Phe Glu Glu Ile Lys Arg Asp
645 650 655
Glu Ser Gly Gly Ile Lys Tyr Lys Lys Ser Gly Lys Pro Glu Tyr Asn
660 665 670
His Gln Arg Arg Asn Phe Ile Leu Asn Asn Val Leu Lys Ser Lys Trp
675 680 685
Phe Phe Tyr Val Val Lys Tyr Asn Arg Pro Ser Ser Cys Arg Glu Leu
690 695 700
Met Lys Asn Lys Glu Ile Leu Arg Phe Val Leu Arg Asp Ile Pro Asp
705 710 715 720
Ser Gln Val Arg Arg Tyr Phe Lys Ala Val Gln Gly Glu Glu Ala Tyr
725 730 735
Ala Ser Ala Glu Ala Met Arg Thr Arg Leu Val Asp Ala Leu Ser Gln
740 745 750
Phe Ser Val Thr Ala Cys Leu Asp Glu Val Gly Gly Met Thr Asp Lys
755 760 765
Glu Phe Ala Ser Gln Arg Ala Val Asp Ser Lys Glu Lys Leu Arg Ala
770 775 780
Ile Ile Arg Leu Tyr Leu Thr Val Ala Tyr Leu Ile Thr Lys Ser Met
785 790 795 800
Val Lys Val Asn Thr Arg Phe Ser Ile Ala Phe Ser Val Leu Glu Arg
805 810 815
Asp Tyr Tyr Leu Leu Ile Asp Gly Lys Lys Lys Ser Ser Asp Tyr Thr
820 825 830
Gly Glu Asp Met Leu Ala Leu Thr Arg Lys Phe Val Gly Glu Asp Ala
835 840 845
Gly Leu Tyr Arg Glu Trp Lys Glu Lys Asn Ala Glu Ala Lys Asp Lys
850 855 860
Tyr Phe Asp Lys Ala Glu Arg Lys Lys Val Leu Arg Gln Asn Asp Lys
865 870 875 880
Met Ile Arg Lys Met His Phe Thr Pro His Ser Leu Asn Tyr Val Gln
885 890 895
Lys Asn Leu Glu Ser Val Gln Ser Asn Gly Leu Ala Ala Val Ile Lys
900 905 910
Glu Tyr Arg Asn Ala Val Ala His Leu Asn Ile Ile Asn Arg Leu Asp
915 920 925
Glu Tyr Ile Gly Ser Ala Arg Ala Asp Ser Tyr Tyr Ser Leu Tyr Cys
930 935 940
Tyr Cys Leu Gln Met Tyr Leu Ser Lys Asn Phe Ser Val Gly Tyr Leu
945 950 955 960
Ile Asn Val Gln Lys Gln Leu Glu Glu His His Thr Tyr Met Lys Asp
965 970 975
Leu Met Trp Leu Leu Asn Ile Pro Phe Ala Tyr Asn Leu Ala Arg Tyr
980 985 990
Lys Asn Leu Ser Asn Glu Lys Leu Phe Tyr Asp Glu Glu Ala Ala Ala
995 1000 1005
Glu Lys Ala Asp Lys Ala Glu Asn Glu Arg Gly Glu
1010 1015 1020
<210> 116
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> RNA酶1(K41R)
<400> 116
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Arg Cys Arg Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asn Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Asn Gly Ser Arg Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val His Phe Asp Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 117
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> RNA酶1 (RNA酶1(K41R, D121E))
<400> 117
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Arg Cys Arg Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asn Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Asn Gly Ser Arg Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val His Phe Glu Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 118
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> RNA酶1 (RNA酶1(K41R, D121E, H119N))
<400> 118
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Arg Cys Arg Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asn Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Asn Gly Ser Arg Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val Asn Phe Glu Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 119
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> (RNA酶1(H119N))
<400> 119
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Arg Cys Lys Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asn Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Asn Gly Ser Arg Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val Asn Phe Asp Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 120
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> (RNA酶1(R39D, N67D, N88A, G89D, R91D, H119N))
<400> 120
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Asp Cys Lys Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asp Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Ala Asp Ser Asp Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val Asn Phe Asp Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 121
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> RNA酶1 (RNA酶1(R39D, N67D, N88A, G89D, R91D, H119N, K41R, D121E))
<400> 121
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Asp Cys Arg Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asp Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Ala Asp Ser Asp Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val Asn Phe Glu Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 122
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> RNA酶1 (RNA酶1(R39D, N67D, N88A, G89D, R91D))
<400> 122
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Asp Cys Lys Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asp Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Ala Asp Ser Asp Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val His Phe Asp Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 123
<211> 311
<212> PRT
<213> 智人（Homo Sapiens）
<400> 123
Cys Ser Pro Gln Glu Ser Gly Met Thr Ala Leu Ser Ala Arg Met Leu
1 5 10 15
Thr Arg Ser Arg Ser Leu Gly Pro Gly Ala Gly Pro Arg Gly Cys Arg
20 25 30
Glu Glu Pro Gly Pro Leu Arg Arg Arg Glu Ala Ala Ala Glu Ala Arg
35 40 45
Lys Ser His Ser Pro Val Lys Arg Pro Arg Lys Ala Gln Arg Leu Arg
50 55 60
Val Ala Tyr Glu Gly Ser Asp Ser Glu Lys Gly Glu Gly Ala Glu Pro
65 70 75 80
Leu Lys Val Pro Val Trp Glu Pro Gln Asp Trp Gln Gln Gln Leu Val
85 90 95
Asn Ile Arg Ala Met Arg Asn Lys Lys Asp Ala Pro Val Asp His Leu
100 105 110
Gly Thr Glu His Cys Tyr Asp Ser Ser Ala Pro Pro Lys Val Arg Arg
115 120 125
Tyr Gln Val Leu Leu Ser Leu Met Leu Ser Ser Gln Thr Lys Asp Gln
130 135 140
Val Thr Ala Gly Ala Met Gln Arg Leu Arg Ala Arg Gly Leu Thr Val
145 150 155 160
Asp Ser Ile Leu Gln Thr Asp Asp Ala Thr Leu Gly Lys Leu Ile Tyr
165 170 175
Pro Val Gly Phe Trp Arg Ser Lys Val Lys Tyr Ile Lys Gln Thr Ser
180 185 190
Ala Ile Leu Gln Gln His Tyr Gly Gly Asp Ile Pro Ala Ser Val Ala
195 200 205
Glu Leu Val Ala Leu Pro Gly Val Gly Pro Lys Met Ala His Leu Ala
210 215 220
Met Ala Val Ala Trp Gly Thr Val Ser Gly Ile Ala Val Asp Thr His
225 230 235 240
Val His Arg Ile Ala Asn Arg Leu Arg Trp Thr Lys Lys Ala Thr Lys
245 250 255
Ser Pro Glu Glu Thr Arg Ala Ala Leu Glu Glu Trp Leu Pro Arg Glu
260 265 270
Leu Trp His Glu Ile Asn Gly Leu Leu Val Gly Phe Gly Gln Gln Thr
275 280 285
Cys Leu Pro Val His Pro Arg Cys His Ala Cys Leu Asn Gln Ala Leu
290 295 300
Cys Pro Ala Ala Gln Gly Leu
305 310
<210> 124
<211> 372
<212> PRT
<213> 智人（Homo Sapiens）
<400> 124
Met Glu Ser Gly Gln Pro Ala Arg Arg Ile Ala Met Ala Pro Leu Leu
1 5 10 15
Glu Tyr Glu Arg Gln Leu Val Leu Glu Leu Leu Asp Thr Asp Gly Leu
20 25 30
Val Val Cys Ala Arg Gly Leu Gly Ala Asp Arg Leu Leu Tyr His Phe
35 40 45
Leu Gln Leu His Cys His Pro Ala Cys Leu Val Leu Val Leu Asn Thr
50 55 60
Gln Pro Ala Glu Glu Glu Tyr Phe Ile Asn Gln Leu Lys Ile Glu Gly
65 70 75 80
Val Glu His Leu Pro Arg Arg Val Thr Asn Glu Ile Thr Ser Asn Ser
85 90 95
Arg Tyr Glu Val Tyr Thr Gln Gly Gly Val Ile Phe Ala Thr Ser Arg
100 105 110
Ile Leu Val Val Asp Phe Leu Thr Asp Arg Ile Pro Ser Asp Leu Ile
115 120 125
Thr Gly Ile Leu Val Tyr Arg Ala His Arg Ile Ile Glu Ser Cys Gln
130 135 140
Glu Ala Phe Ile Leu Arg Leu Phe Arg Gln Lys Asn Lys Arg Gly Phe
145 150 155 160
Ile Lys Ala Phe Thr Asp Asn Ala Val Ala Phe Asp Thr Gly Phe Cys
165 170 175
His Val Glu Arg Val Met Arg Asn Leu Phe Val Arg Lys Leu Tyr Leu
180 185 190
Trp Pro Arg Phe His Val Ala Val Asn Ser Phe Leu Glu Gln His Lys
195 200 205
Pro Glu Val Val Glu Ile His Val Ser Met Thr Pro Thr Met Leu Ala
210 215 220
Ile Gln Thr Ala Ile Leu Asp Ile Leu Asn Ala Cys Leu Lys Glu Leu
225 230 235 240
Lys Cys His Asn Pro Ser Leu Glu Val Glu Asp Leu Ser Leu Glu Asn
245 250 255
Ala Ile Gly Lys Pro Phe Asp Lys Thr Ile Arg His Tyr Leu Asp Pro
260 265 270
Leu Trp His Gln Leu Gly Ala Lys Thr Lys Ser Leu Val Gln Asp Leu
275 280 285
Lys Ile Leu Arg Thr Leu Leu Gln Tyr Leu Ser Gln Tyr Asp Cys Val
290 295 300
Thr Phe Leu Asn Leu Leu Glu Ser Leu Arg Ala Thr Glu Lys Ala Phe
305 310 315 320
Gly Gln Asn Ser Gly Trp Leu Phe Leu Asp Ser Ser Thr Ser Met Phe
325 330 335
Ile Asn Ala Arg Ala Arg Val Tyr His Leu Pro Asp Ala Lys Met Ser
340 345 350
Lys Lys Glu Lys Ile Ser Glu Lys Met Glu Ile Lys Glu Gly Glu Gly
355 360 365
Ile Leu Trp Gly
370
<210> 125
<211> 287
<212> PRT
<213> 智人（Homo Sapiens）
<400> 125
Pro Lys Arg Gly Lys Lys Gly Ala Val Ala Glu Asp Gly Asp Glu Leu
1 5 10 15
Arg Thr Glu Pro Glu Ala Lys Lys Ser Lys Thr Ala Ala Lys Lys Asn
20 25 30
Asp Lys Glu Ala Ala Gly Glu Gly Pro Ala Leu Tyr Glu Asp Pro Pro
35 40 45
Asp Gln Lys Thr Ser Pro Ser Gly Lys Pro Ala Thr Leu Lys Ile Cys
50 55 60
Ser Trp Asn Val Asp Gly Leu Arg Ala Trp Ile Lys Lys Lys Gly Leu
65 70 75 80
Asp Trp Val Lys Glu Glu Ala Pro Asp Ile Leu Cys Leu Gln Glu Thr
85 90 95
Lys Cys Ser Glu Asn Lys Leu Pro Ala Glu Leu Gln Glu Leu Pro Gly
100 105 110
Leu Ser His Gln Tyr Trp Ser Ala Pro Ser Asp Lys Glu Gly Tyr Ser
115 120 125
Gly Val Gly Leu Leu Ser Arg Gln Cys Pro Leu Lys Val Ser Tyr Gly
130 135 140
Ile Gly Asp Glu Glu His Asp Gln Glu Gly Arg Val Ile Val Ala Glu
145 150 155 160
Phe Asp Ser Phe Val Leu Val Thr Ala Tyr Val Pro Asn Ala Gly Arg
165 170 175
Gly Leu Val Arg Leu Glu Tyr Arg Gln Arg Trp Asp Glu Ala Phe Arg
180 185 190
Lys Phe Leu Lys Gly Leu Ala Ser Arg Lys Pro Leu Val Leu Cys Gly
195 200 205
Asp Leu Asn Val Ala His Glu Glu Ile Asp Leu Arg Asn Pro Lys Gly
210 215 220
Asn Lys Lys Asn Ala Gly Phe Thr Pro Gln Glu Arg Gln Gly Phe Gly
225 230 235 240
Glu Leu Leu Gln Ala Val Pro Leu Ala Asp Ser Phe Arg His Leu Tyr
245 250 255
Pro Asn Thr Pro Tyr Ala Tyr Thr Phe Trp Thr Tyr Met Met Asn Ala
260 265 270
Arg Ser Lys Asn Val Gly Trp Arg Leu Asp Tyr Phe Leu Leu Ser
275 280 285
<210> 126
<211> 213
<212> PRT
<213> 智人（Homo Sapiens）
<400> 126
Glu Ala Leu Phe Phe Pro Ser Gln Val Thr Cys Thr Glu Ala Leu Leu
1 5 10 15
Arg Ala Pro Gly Ala Glu Leu Ala Glu Leu Pro Glu Gly Cys Pro Cys
20 25 30
Gly Leu Pro His Gly Glu Ser Ala Leu Ser Arg Leu Leu Arg Ala Leu
35 40 45
Leu Ala Ala Arg Ala Ser Leu Asp Leu Cys Leu Phe Ala Phe Ser Ser
50 55 60
Pro Gln Leu Gly Arg Ala Val Gln Leu Leu His Gln Arg Gly Val Arg
65 70 75 80
Val Arg Val Val Thr Asp Cys Asp Tyr Met Ala Leu Asn Gly Ser Gln
85 90 95
Ile Gly Leu Leu Arg Lys Ala Gly Ile Gln Val Arg His Asp Gln Asp
100 105 110
Pro Gly Tyr Met His His Lys Phe Ala Ile Val Asp Lys Arg Val Leu
115 120 125
Ile Thr Gly Ser Leu Asn Trp Thr Thr Gln Ala Ile Gln Asn Asn Arg
130 135 140
Glu Asn Val Leu Ile Thr Glu Asp Asp Glu Tyr Val Arg Leu Phe Leu
145 150 155 160
Glu Glu Phe Glu Arg Ile Trp Glu Gln Phe Asn Pro Thr Lys Tyr Thr
165 170 175
Phe Phe Pro Pro Lys Lys Ser His Gly Ser Cys Ala Pro Pro Val Ser
180 185 190
Arg Ala Gly Gly Arg Leu Leu Ser Trp His Arg Thr Cys Gly Thr Ser
195 200 205
Ser Glu Ser Gln Thr
210
<210> 127
<211> 382
<212> PRT
<213> 智人（Homo Sapiens）
<400> 127
Lys Ala Arg Tyr Lys Thr Leu Glu Pro Arg Gly Tyr Ser Leu Leu Ile
1 5 10 15
Arg Gly Leu Ile His Ser Asp Arg Trp Arg Glu Ala Leu Leu Leu Leu
20 25 30
Glu Asp Ile Lys Lys Val Ile Thr Pro Ser Lys Lys Asn Tyr Asn Asp
35 40 45
Cys Ile Gln Gly Ala Leu Leu His Gln Asp Val Asn Thr Ala Trp Asn
50 55 60
Leu Tyr Gln Glu Leu Leu Gly His Asp Ile Val Pro Met Leu Glu Thr
65 70 75 80
Leu Lys Ala Phe Phe Asp Phe Gly Lys Asp Ile Lys Asp Asp Asn Tyr
85 90 95
Ser Asn Lys Leu Leu Asp Ile Leu Ser Tyr Leu Arg Asn Asn Gln Leu
100 105 110
Tyr Pro Gly Glu Ser Phe Ala His Ser Ile Lys Thr Trp Phe Glu Ser
115 120 125
Val Pro Gly Lys Gln Trp Lys Gly Gln Phe Thr Thr Val Arg Lys Ser
130 135 140
Gly Gln Cys Ser Gly Cys Gly Lys Thr Ile Glu Ser Ile Gln Leu Ser
145 150 155 160
Pro Glu Glu Tyr Glu Cys Leu Lys Gly Lys Ile Met Arg Asp Val Ile
165 170 175
Asp Gly Gly Asp Gln Tyr Arg Lys Thr Thr Pro Gln Glu Leu Lys Arg
180 185 190
Phe Glu Asn Phe Ile Lys Ser Arg Pro Pro Phe Asp Val Val Ile Asp
195 200 205
Gly Leu Asn Val Ala Lys Met Phe Pro Lys Val Arg Glu Ser Gln Leu
210 215 220
Leu Leu Asn Val Val Ser Gln Leu Ala Lys Arg Asn Leu Arg Leu Leu
225 230 235 240
Val Leu Gly Arg Lys His Met Leu Arg Arg Ser Ser Gln Trp Ser Arg
245 250 255
Asp Glu Met Glu Glu Val Gln Lys Gln Ala Ser Cys Phe Phe Ala Asp
260 265 270
Asp Ile Ser Glu Asp Asp Pro Phe Leu Leu Tyr Ala Thr Leu His Ser
275 280 285
Gly Asn His Cys Arg Phe Ile Thr Arg Asp Leu Met Arg Asp His Lys
290 295 300
Ala Cys Leu Pro Asp Ala Lys Thr Gln Arg Leu Phe Phe Lys Trp Gln
305 310 315 320
Gln Gly His Gln Leu Ala Ile Val Asn Arg Phe Pro Gly Ser Lys Leu
325 330 335
Thr Phe Gln Arg Ile Leu Ser Tyr Asp Thr Val Val Gln Thr Thr Gly
340 345 350
Asp Ser Trp His Ile Pro Tyr Asp Glu Asp Leu Val Glu Arg Cys Ser
355 360 365
Cys Glu Val Pro Thr Lys Trp Leu Cys Leu His Gln Lys Thr
370 375 380
<210> 128
<211> 360
<212> PRT
<213> 智人（Homo Sapiens）
<400> 128
Ser Val Glu Pro Met Phe Arg His Leu Lys Asn Thr Tyr Ala Gly Leu
1 5 10 15
Gln Leu Val Val Val Ile Leu Pro Gly Lys Thr Pro Val Tyr Ala Glu
20 25 30
Val Lys Arg Val Gly Asp Thr Val Leu Gly Met Ala Thr Gln Cys Val
35 40 45
Gln Met Lys Asn Val Gln Arg Thr Thr Pro Gln Thr Leu Ser Asn Leu
50 55 60
Cys Leu Lys Ile Asn Val Lys Leu Gly Gly Val Asn Asn Ile Leu Leu
65 70 75 80
Pro Gln Gly Arg Pro Pro Val Phe Gln Gln Pro Val Ile Phe Leu Gly
85 90 95
Ala Asp Val Thr His Pro Pro Ala Gly Asp Gly Lys Lys Pro Ser Ile
100 105 110
Ala Ala Val Val Gly Ser Met Asp Ala His Pro Asn Arg Tyr Cys Ala
115 120 125
Thr Val Arg Val Gln Gln His Arg Gln Glu Ile Ile Gln Asp Leu Ala
130 135 140
Ala Met Val Arg Glu Leu Leu Ile Gln Phe Tyr Lys Ser Thr Arg Phe
145 150 155 160
Lys Pro Thr Arg Ile Ile Phe Tyr Arg Asp Gly Val Ser Glu Gly Gln
165 170 175
Phe Gln Gln Val Leu His His Glu Leu Leu Ala Ile Arg Glu Ala Cys
180 185 190
Ile Lys Leu Glu Lys Asp Tyr Gln Pro Gly Ile Thr Phe Ile Val Val
195 200 205
Gln Lys Arg His His Thr Arg Leu Phe Cys Thr Asp Lys Asn Glu Arg
210 215 220
Val Gly Lys Ser Gly Asn Ile Pro Ala Gly Thr Thr Val Asp Thr Lys
225 230 235 240
Ile Thr His Pro Thr Glu Phe Asp Phe Tyr Leu Cys Ser His Ala Gly
245 250 255
Ile Gln Gly Thr Ser Arg Pro Ser His Tyr His Val Leu Trp Asp Asp
260 265 270
Asn Arg Phe Ser Ser Asp Glu Leu Gln Ile Leu Thr Tyr Gln Leu Cys
275 280 285
His Thr Tyr Val Arg Cys Thr Arg Ser Val Ser Ile Pro Ala Pro Ala
290 295 300
Tyr Tyr Ala His Leu Val Ala Phe Arg Ala Arg Tyr His Leu Val Asp
305 310 315 320
Lys Glu His Asp Ser Ala Glu Gly Ser His Thr Ser Gly Gln Ser Asn
325 330 335
Gly Arg Asp His Gln Ala Leu Ala Lys Ala Val Gln Val His Gln Asp
340 345 350
Thr Leu Arg Thr Met Tyr Phe Ala
355 360
<210> 129
<211> 327
<212> PRT
<213> 智人（Homo Sapiens）
<400> 129
Gln Gly Ala Glu Gly Ala Leu Thr Gly Lys Gln Pro Asp Gly Ser Ala
1 5 10 15
Glu Lys Ala Val Leu Glu Gln Phe Gly Phe Pro Leu Thr Gly Thr Glu
20 25 30
Ala Arg Cys Tyr Thr Asn His Ala Leu Ser Tyr Asp Gln Ala Lys Arg
35 40 45
Val Pro Arg Trp Val Leu Glu His Ile Ser Lys Ser Lys Ile Met Gly
50 55 60
Asp Ala Asp Arg Lys His Cys Lys Phe Lys Pro Asp Pro Asn Ile Pro
65 70 75 80
Pro Thr Phe Ser Ala Phe Asn Glu Asp Tyr Val Gly Ser Gly Trp Ser
85 90 95
Arg Gly His Met Ala Pro Ala Gly Asn Asn Lys Phe Ser Ser Lys Ala
100 105 110
Met Ala Glu Thr Phe Tyr Leu Ser Asn Ile Val Pro Gln Asp Phe Asp
115 120 125
Asn Asn Ser Gly Tyr Trp Asn Arg Ile Glu Met Tyr Cys Arg Glu Leu
130 135 140
Thr Glu Arg Phe Glu Asp Val Trp Val Val Ser Gly Pro Leu Thr Leu
145 150 155 160
Pro Gln Thr Arg Gly Asp Gly Lys Lys Ile Val Ser Tyr Gln Val Ile
165 170 175
Gly Glu Asp Asn Val Ala Val Pro Ser His Leu Tyr Lys Val Ile Leu
180 185 190
Ala Arg Arg Ser Ser Val Ser Thr Glu Pro Leu Ala Leu Gly Ala Phe
195 200 205
Val Val Pro Asn Glu Ala Ile Gly Phe Gln Pro Gln Leu Thr Glu Phe
210 215 220
Gln Val Ser Leu Gln Asp Leu Glu Lys Leu Ser Gly Leu Val Phe Phe
225 230 235 240
Pro His Leu Asp Arg Thr Ser Asp Ile Arg Asn Ile Cys Ser Val Asp
245 250 255
Thr Cys Lys Leu Leu Asp Phe Gln Glu Phe Thr Leu Tyr Leu Ser Thr
260 265 270
Arg Lys Ile Glu Gly Ala Arg Ser Val Leu Arg Leu Glu Lys Ile Met
275 280 285
Glu Asn Leu Lys Asn Ala Glu Ile Glu Pro Asp Asp Tyr Phe Met Ser
290 295 300
Arg Tyr Glu Lys Lys Leu Glu Glu Leu Lys Ala Lys Glu Gln Ser Gly
305 310 315 320
Thr Gln Ile Arg Lys Pro Ser
325
<210> 130
<211> 526
<212> PRT
<213> 智人（Homo Sapiens）
<400> 130
Glu His Pro Ser Lys Met Glu Phe Phe Gln Lys Leu Gly Tyr Asp Arg
1 5 10 15
Glu Asp Val Leu Arg Val Leu Gly Lys Leu Gly Glu Gly Ala Leu Val
20 25 30
Asn Asp Val Leu Gln Glu Leu Ile Arg Thr Gly Ser Arg Pro Gly Ala
35 40 45
Leu Glu His Pro Ala Ala Pro Arg Leu Val Pro Arg Gly Ser Cys Gly
50 55 60
Val Pro Asp Ser Ala Gln Arg Gly Pro Gly Thr Ala Leu Glu Glu Asp
65 70 75 80
Phe Arg Thr Leu Ala Ser Ser Leu Arg Pro Ile Val Ile Asp Gly Ser
85 90 95
Asn Val Ala Met Ser His Gly Asn Lys Glu Thr Phe Ser Cys Arg Gly
100 105 110
Ile Lys Leu Ala Val Asp Trp Phe Arg Asp Arg Gly His Thr Tyr Ile
115 120 125
Lys Val Phe Val Pro Ser Trp Arg Lys Asp Pro Pro Arg Ala Asp Thr
130 135 140
Pro Ile Arg Glu Gln His Val Leu Ala Glu Leu Glu Arg Gln Ala Val
145 150 155 160
Leu Val Tyr Thr Pro Ser Arg Lys Val His Gly Lys Arg Leu Val Cys
165 170 175
Tyr Asp Asp Arg Tyr Ile Val Lys Val Ala Tyr Glu Gln Asp Gly Val
180 185 190
Ile Val Ser Asn Asp Asn Tyr Arg Asp Leu Gln Ser Glu Asn Pro Glu
195 200 205
Trp Lys Trp Phe Ile Glu Gln Arg Leu Leu Met Phe Ser Phe Val Asn
210 215 220
Asp Arg Phe Met Pro Pro Asp Asp Pro Leu Gly Arg His Gly Pro Ser
225 230 235 240
Leu Ser Asn Phe Leu Ser Arg Lys Pro Lys Pro Pro Glu Pro Ser Trp
245 250 255
Gln His Cys Pro Tyr Gly Lys Lys Cys Thr Tyr Gly Ile Lys Cys Lys
260 265 270
Phe Tyr His Pro Glu Arg Pro His His Ala Gln Leu Ala Val Ala Asp
275 280 285
Glu Leu Arg Ala Lys Thr Gly Ala Arg Pro Gly Ala Gly Ala Glu Glu
290 295 300
Gln Arg Pro Pro Arg Ala Pro Gly Gly Ser Ala Gly Ala Arg Ala Ala
305 310 315 320
Pro Arg Glu Pro Phe Ala His Ser Leu Pro Pro Ala Arg Gly Ser Pro
325 330 335
Asp Leu Ala Ala Leu Arg Gly Ser Phe Ser Arg Leu Ala Phe Ser Asp
340 345 350
Asp Leu Gly Pro Leu Gly Pro Pro Leu Pro Val Pro Ala Cys Ser Leu
355 360 365
Thr Pro Arg Leu Gly Gly Pro Asp Trp Val Ser Ala Gly Gly Arg Val
370 375 380
Pro Gly Pro Leu Ser Leu Pro Ser Pro Glu Ser Gln Phe Ser Pro Gly
385 390 395 400
Asp Leu Pro Pro Pro Pro Gly Leu Gln Leu Gln Pro Arg Gly Glu His
405 410 415
Arg Pro Arg Asp Leu His Gly Asp Leu Leu Ser Pro Arg Arg Pro Pro
420 425 430
Asp Asp Pro Trp Ala Arg Pro Pro Arg Ser Asp Arg Phe Pro Gly Arg
435 440 445
Ser Val Trp Ala Glu Pro Ala Trp Gly Asp Gly Ala Thr Gly Gly Leu
450 455 460
Ser Val Tyr Ala Thr Glu Asp Asp Glu Gly Asp Ala Arg Ala Arg Ala
465 470 475 480
Arg Ile Ala Leu Tyr Ser Val Phe Pro Arg Asp Gln Val Asp Arg Val
485 490 495
Met Ala Ala Phe Pro Glu Leu Ser Asp Leu Ala Arg Leu Ile Leu Leu
500 505 510
Val Gln Arg Cys Gln Ser Ala Gly Ala Pro Leu Gly Lys Pro
515 520 525
<210> 131
<211> 475
<212> PRT
<213> 智人（Homo Sapiens）
<400> 131
Arg Gln Gln Gln Pro Gln Val Val Glu Lys Gln Gln Glu Thr Pro Leu
1 5 10 15
Ala Pro Ala Asp Phe Ala His Ile Ser Gln Asp Ala Gln Ser Leu His
20 25 30
Ser Gly Ala Ser Arg Arg Ser Gln Lys Arg Leu Gln Ser Pro Ser Lys
35 40 45
Gln Ala Gln Pro Leu Asp Asp Pro Glu Ala Glu Gln Leu Thr Val Val
50 55 60
Gly Lys Ile Ser Phe Asn Pro Lys Asp Val Leu Gly Arg Gly Ala Gly
65 70 75 80
Gly Thr Phe Val Phe Arg Gly Gln Phe Glu Gly Arg Ala Val Ala Val
85 90 95
Lys Arg Leu Leu Arg Glu Cys Phe Gly Leu Val Arg Arg Glu Val Gln
100 105 110
Leu Leu Gln Glu Ser Asp Arg His Pro Asn Val Leu Arg Tyr Phe Cys
115 120 125
Thr Glu Arg Gly Pro Gln Phe His Tyr Ile Ala Leu Glu Leu Cys Arg
130 135 140
Ala Ser Leu Gln Glu Tyr Val Glu Asn Pro Asp Leu Asp Arg Gly Gly
145 150 155 160
Leu Glu Pro Glu Val Val Leu Gln Gln Leu Met Ser Gly Leu Ala His
165 170 175
Leu His Ser Leu His Ile Val His Arg Asp Leu Lys Pro Gly Asn Ile
180 185 190
Leu Ile Thr Gly Pro Asp Ser Gln Gly Leu Gly Arg Val Val Leu Ser
195 200 205
Asp Phe Gly Leu Cys Lys Lys Leu Pro Ala Gly Arg Cys Ser Phe Ser
210 215 220
Leu His Ser Gly Ile Pro Gly Thr Glu Gly Trp Met Ala Pro Glu Leu
225 230 235 240
Leu Gln Leu Leu Pro Pro Asp Ser Pro Thr Ser Ala Val Asp Ile Phe
245 250 255
Ser Ala Gly Cys Val Phe Tyr Tyr Val Leu Ser Gly Gly Ser His Pro
260 265 270
Phe Gly Asp Ser Leu Tyr Arg Gln Ala Asn Ile Leu Thr Gly Ala Pro
275 280 285
Cys Leu Ala His Leu Glu Glu Glu Val His Asp Lys Val Val Ala Arg
290 295 300
Asp Leu Val Gly Ala Met Leu Ser Pro Leu Pro Gln Pro Arg Pro Ser
305 310 315 320
Ala Pro Gln Val Leu Ala His Pro Phe Phe Trp Ser Arg Ala Lys Gln
325 330 335
Leu Gln Phe Phe Gln Asp Val Ser Asp Trp Leu Glu Lys Glu Ser Glu
340 345 350
Gln Glu Pro Leu Val Arg Ala Leu Glu Ala Gly Gly Cys Ala Val Val
355 360 365
Arg Asp Asn Trp His Glu His Ile Ser Met Pro Leu Gln Thr Asp Leu
370 375 380
Arg Lys Phe Arg Ser Tyr Lys Gly Thr Ser Val Arg Asp Leu Leu Arg
385 390 395 400
Ala Val Arg Asn Lys Lys His His Tyr Arg Glu Leu Pro Val Glu Val
405 410 415
Arg Gln Ala Leu Gly Gln Val Pro Asp Gly Phe Val Gln Tyr Phe Thr
420 425 430
Asn Arg Phe Pro Arg Leu Leu Leu His Thr His Arg Ala Met Arg Ser
435 440 445
Cys Ala Ser Glu Ser Leu Phe Leu Pro Tyr Tyr Pro Pro Asp Ser Glu
450 455 460
Ala Arg Arg Pro Cys Pro Gly Ala Thr Gly Arg
465 470 475
<210> 132
<211> 384
<212> PRT
<213> 智人（Homo Sapiens）
<400> 132
Lys Leu Val Arg Lys Asn Ile Glu Lys Asp Asn Ala Gly Gln Val Thr
1 5 10 15
Leu Val Pro Glu Glu Pro Glu Asp Met Trp His Thr Tyr Asn Leu Val
20 25 30
Gln Val Gly Asp Ser Leu Arg Ala Ser Thr Ile Arg Lys Val Gln Thr
35 40 45
Glu Ser Ser Thr Gly Ser Val Gly Ser Asn Arg Val Arg Thr Thr Leu
50 55 60
Thr Leu Cys Val Glu Ala Ile Asp Phe Asp Ser Gln Ala Cys Gln Leu
65 70 75 80
Arg Val Lys Gly Thr Asn Ile Gln Glu Asn Glu Tyr Val Lys Met Gly
85 90 95
Ala Tyr His Thr Ile Glu Leu Glu Pro Asn Arg Gln Phe Thr Leu Ala
100 105 110
Lys Lys Gln Trp Asp Ser Val Val Leu Glu Arg Ile Glu Gln Ala Cys
115 120 125
Asp Pro Ala Trp Ser Ala Asp Val Ala Ala Val Val Met Gln Glu Gly
130 135 140
Leu Ala His Ile Cys Leu Val Thr Pro Ser Met Thr Leu Thr Arg Ala
145 150 155 160
Lys Val Glu Val Asn Ile Pro Arg Lys Arg Lys Gly Asn Cys Ser Gln
165 170 175
His Asp Arg Ala Leu Glu Arg Phe Tyr Glu Gln Val Val Gln Ala Ile
180 185 190
Gln Arg His Ile His Phe Asp Val Val Lys Cys Ile Leu Val Ala Ser
195 200 205
Pro Gly Phe Val Arg Glu Gln Phe Cys Asp Tyr Leu Phe Gln Gln Ala
210 215 220
Val Lys Thr Asp Asn Lys Leu Leu Leu Glu Asn Arg Ser Lys Phe Leu
225 230 235 240
Gln Val His Ala Ser Ser Gly His Lys Tyr Ser Leu Lys Glu Ala Leu
245 250 255
Cys Asp Pro Thr Val Ala Ser Arg Leu Ser Asp Thr Lys Ala Ala Gly
260 265 270
Glu Val Lys Ala Leu Asp Asp Phe Tyr Lys Met Leu Gln His Glu Pro
275 280 285
Asp Arg Ala Phe Tyr Gly Leu Lys Gln Val Glu Lys Ala Asn Glu Ala
290 295 300
Met Ala Ile Asp Thr Leu Leu Ile Ser Asp Glu Leu Phe Arg His Gln
305 310 315 320
Asp Val Ala Thr Arg Ser Arg Tyr Val Arg Leu Val Asp Ser Val Lys
325 330 335
Glu Asn Ala Gly Thr Val Arg Ile Phe Ser Ser Leu His Val Ser Gly
340 345 350
Glu Gln Leu Ser Gln Leu Thr Gly Val Ala Ala Ile Leu Arg Phe Pro
355 360 365
Val Pro Glu Leu Ser Asp Gln Glu Gly Asp Ser Ser Ser Glu Glu Asp
370 375 380
<210> 133
<211> 166
<212> PRT
<213> 智人（Homo Sapiens）
<400> 133
Ser Leu Val Ile Arg Asn Leu Gln Arg Val Ile Pro Ile Arg Arg Ala
1 5 10 15
Pro Leu Arg Ser Lys Ile Glu Ile Val Arg Arg Ile Leu Gly Val Gln
20 25 30
Lys Phe Asp Leu Gly Ile Ile Cys Val Asp Asn Lys Asn Ile Gln His
35 40 45
Ile Asn Arg Ile Tyr Arg Asp Arg Asn Val Pro Thr Asp Val Leu Ser
50 55 60
Phe Pro Phe His Glu His Leu Lys Ala Gly Glu Phe Pro Gln Pro Asp
65 70 75 80
Phe Pro Asp Asp Tyr Asn Leu Gly Asp Ile Phe Leu Gly Val Glu Tyr
85 90 95
Ile Phe His Gln Cys Lys Glu Asn Glu Asp Tyr Asn Asp Val Leu Thr
100 105 110
Val Thr Ala Thr His Gly Leu Cys His Leu Leu Gly Phe Thr His Gly
115 120 125
Thr Glu Ala Glu Trp Gln Gln Met Phe Gln Lys Glu Lys Ala Val Leu
130 135 140
Asp Glu Leu Gly Arg Arg Thr Gly Thr Arg Leu Gln Pro Leu Thr Arg
145 150 155 160
Gly Leu Phe Gly Gly Ser
165
<210> 134
<211> 178
<212> PRT
<213> 智人（Homo Sapiens）
<400> 134
Gln Glu Val Ile Ala Gly Leu Glu Arg Phe Thr Phe Ala Phe Glu Lys
1 5 10 15
Asp Val Glu Met Gln Lys Gly Thr Gly Leu Leu Pro Phe Gln Gly Met
20 25 30
Asp Lys Ser Ala Ser Ala Val Cys Asn Phe Phe Thr Lys Gly Leu Cys
35 40 45
Glu Lys Gly Lys Leu Cys Pro Phe Arg His Asp Arg Gly Glu Lys Met
50 55 60
Val Val Cys Lys His Trp Leu Arg Gly Leu Cys Lys Lys Gly Asp His
65 70 75 80
Cys Lys Phe Leu His Gln Tyr Asp Leu Thr Arg Met Pro Glu Cys Tyr
85 90 95
Phe Tyr Ser Lys Phe Gly Asp Cys Ser Asn Lys Glu Cys Ser Phe Leu
100 105 110
His Val Lys Pro Ala Phe Lys Ser Gln Asp Cys Pro Trp Tyr Asp Gln
115 120 125
Gly Phe Cys Lys Asp Gly Pro Leu Cys Lys Tyr Arg His Val Pro Arg
130 135 140
Ile Met Cys Leu Asn Tyr Leu Val Gly Phe Cys Pro Glu Gly Pro Lys
145 150 155 160
Cys Gln Phe Ala Gln Lys Ile Arg Glu Phe Lys Leu Leu Pro Gly Ser
165 170 175
Lys Ile
<210> 135
<211> 384
<212> PRT
<213> 智人（Homo Sapiens）
<400> 135
Lys Leu Val Arg Lys Asn Ile Glu Lys Asp Asn Ala Gly Gln Val Thr
1 5 10 15
Leu Val Pro Glu Glu Pro Glu Asp Met Trp His Thr Tyr Asn Leu Val
20 25 30
Gln Val Gly Asp Ser Leu Arg Ala Ser Thr Ile Arg Lys Val Gln Thr
35 40 45
Glu Ser Ser Thr Gly Ser Val Gly Ser Asn Arg Val Arg Thr Thr Leu
50 55 60
Thr Leu Cys Val Glu Ala Ile Asp Phe Asp Ser Gln Ala Cys Gln Leu
65 70 75 80
Arg Val Lys Gly Thr Asn Ile Gln Glu Asn Glu Tyr Val Lys Met Gly
85 90 95
Ala Tyr His Thr Ile Glu Leu Glu Pro Asn Arg Gln Phe Thr Leu Ala
100 105 110
Lys Lys Gln Trp Asp Ser Val Val Leu Glu Arg Ile Glu Gln Ala Cys
115 120 125
Asp Pro Ala Trp Ser Ala Asp Val Ala Ala Val Val Met Gln Glu Gly
130 135 140
Leu Ala His Ile Cys Leu Val Thr Pro Ser Met Thr Leu Thr Arg Ala
145 150 155 160
Lys Val Glu Val Asn Ile Pro Arg Lys Arg Lys Gly Asn Cys Ser Gln
165 170 175
His Asp Arg Ala Leu Glu Arg Phe Tyr Glu Gln Val Val Gln Ala Ile
180 185 190
Gln Arg His Ile His Phe Asp Val Val Lys Cys Ile Leu Val Ala Ser
195 200 205
Pro Gly Phe Val Arg Glu Gln Phe Cys Asp Tyr Met Phe Gln Gln Ala
210 215 220
Val Lys Thr Asp Asn Lys Leu Leu Leu Glu Asn Arg Ser Lys Phe Leu
225 230 235 240
Gln Val His Ala Ser Ser Gly His Lys Tyr Ser Leu Lys Glu Ala Leu
245 250 255
Cys Asp Pro Thr Val Ala Ser Arg Leu Ser Asp Thr Lys Ala Ala Gly
260 265 270
Glu Val Lys Ala Leu Asp Asp Phe Tyr Lys Met Leu Gln His Glu Pro
275 280 285
Asp Arg Ala Phe Tyr Gly Leu Lys Gln Val Glu Lys Ala Asn Glu Ala
290 295 300
Met Ala Ile Asp Thr Leu Leu Ile Ser Asp Glu Leu Phe Arg His Gln
305 310 315 320
Asp Val Ala Thr Arg Ser Arg Tyr Val Arg Leu Val Asp Ser Val Lys
325 330 335
Glu Asn Ala Gly Thr Val Arg Ile Phe Ser Ser Leu His Val Ser Gly
340 345 350
Glu Gln Leu Ser Gln Leu Thr Gly Val Ala Ala Ile Leu Arg Phe Pro
355 360 365
Val Pro Glu Leu Ser Asp Gln Glu Gly Asp Ser Ser Ser Glu Glu Asp
370 375 380
<210> 136
<211> 256
<212> PRT
<213> 智人（Homo Sapiens）
<400> 136
Asp Pro Ala Trp Ser Ala Asp Val Ala Ala Val Val Met Gln Glu Gly
1 5 10 15
Leu Ala His Ile Cys Leu Val Thr Pro Ser Met Thr Leu Thr Arg Ala
20 25 30
Lys Val Glu Val Asn Ile Pro Arg Lys Arg Lys Gly Asn Cys Ser Gln
35 40 45
His Asp Arg Ala Leu Glu Arg Phe Tyr Glu Gln Val Val Gln Ala Ile
50 55 60
Gln Arg His Ile His Phe Asp Val Val Lys Cys Ile Leu Val Ala Ser
65 70 75 80
Pro Gly Phe Val Arg Glu Gln Phe Cys Asp Tyr Met Phe Gln Gln Ala
85 90 95
Val Lys Thr Asp Asn Lys Leu Leu Leu Glu Asn Arg Ser Lys Phe Leu
100 105 110
Gln Val His Ala Ser Ser Gly His Lys Tyr Ser Leu Lys Glu Ala Leu
115 120 125
Cys Asp Pro Thr Val Ala Ser Arg Leu Ser Asp Thr Lys Ala Ala Gly
130 135 140
Glu Val Lys Ala Leu Asp Asp Phe Tyr Lys Met Leu Gln His Glu Pro
145 150 155 160
Asp Arg Ala Phe Tyr Gly Leu Lys Gln Val Glu Lys Ala Asn Glu Ala
165 170 175
Met Ala Ile Asp Thr Leu Leu Ile Ser Asp Glu Leu Phe Arg His Gln
180 185 190
Asp Val Ala Thr Arg Ser Arg Tyr Val Arg Leu Val Asp Ser Val Lys
195 200 205
Glu Asn Ala Gly Thr Val Arg Ile Phe Ser Ser Leu His Val Ser Gly
210 215 220
Glu Gln Leu Ser Gln Leu Thr Gly Val Ala Ala Ile Leu Arg Phe Pro
225 230 235 240
Val Pro Glu Leu Ser Asp Gln Glu Gly Asp Ser Ser Ser Glu Glu Asp
245 250 255
<210> 137
<211> 209
<212> PRT
<213> 智人（Homo Sapiens）
<400> 137
Met Asp Pro Gly Lys Asp Lys Glu Gly Val Pro Gln Pro Ser Gly Pro
1 5 10 15
Pro Ala Arg Lys Lys Phe Val Ile Pro Leu Asp Glu Asp Glu Val Pro
20 25 30
Pro Gly Val Arg Gly Asn Pro Val Leu Lys Phe Val Arg Asn Val Pro
35 40 45
Trp Glu Phe Gly Asp Val Ile Pro Asp Tyr Val Leu Gly Gln Ser Thr
50 55 60
Cys Ala Leu Phe Leu Ser Leu Arg Tyr His Asn Leu His Pro Asp Tyr
65 70 75 80
Ile His Gly Arg Leu Gln Ser Leu Gly Lys Asn Phe Ala Leu Arg Val
85 90 95
Leu Leu Val Gln Val Asp Val Lys Asp Pro Gln Gln Ala Leu Lys Glu
100 105 110
Leu Ala Lys Met Cys Ile Leu Ala Asp Cys Thr Leu Ile Leu Ala Trp
115 120 125
Ser Pro Glu Glu Ala Gly Arg Tyr Leu Glu Thr Tyr Lys Ala Tyr Glu
130 135 140
Gln Lys Pro Ala Asp Leu Leu Met Glu Lys Leu Glu Gln Asp Phe Val
145 150 155 160
Ser Arg Val Thr Glu Cys Leu Thr Thr Val Lys Ser Val Asn Lys Thr
165 170 175
Asp Ser Gln Thr Leu Leu Thr Thr Phe Gly Ser Leu Glu Gln Leu Ile
180 185 190
Ala Ala Ser Arg Glu Asp Leu Ala Leu Cys Pro Gly Leu Gly Pro Gln
195 200 205
Lys
<210> 138
<211> 128
<212> PRT
<213> 智人（Homo Sapiens）
<400> 138
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Arg Cys Lys Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asn Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Asn Gly Ser Arg Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val His Phe Asp Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 139
<211> 123
<212> PRT
<213> 智人（Homo Sapiens）
<400> 139
Gln Asp Asn Ser Arg Tyr Thr His Phe Leu Thr Gln His Tyr Asp Ala
1 5 10 15
Lys Pro Gln Gly Arg Asp Asp Arg Tyr Cys Glu Ser Ile Met Arg Arg
20 25 30
Arg Gly Leu Thr Ser Pro Cys Lys Asp Ile Asn Thr Phe Ile His Gly
35 40 45
Asn Lys Arg Ser Ile Lys Ala Ile Cys Glu Asn Lys Asn Gly Asn Pro
50 55 60
His Arg Glu Asn Leu Arg Ile Ser Lys Ser Ser Phe Gln Val Thr Thr
65 70 75 80
Cys Lys Leu His Gly Gly Ser Pro Trp Pro Pro Cys Gln Tyr Arg Ala
85 90 95
Thr Ala Gly Phe Arg Asn Val Val Val Ala Cys Glu Asn Gly Leu Pro
100 105 110
Val His Leu Asp Gln Ser Ile Phe Arg Arg Pro
115 120
<210> 140
<211> 129
<212> PRT
<213> 智人（Homo Sapiens）
<400> 140
Gly Leu Gly Leu Val Gln Pro Ser Tyr Gly Gln Asp Gly Met Tyr Gln
1 5 10 15
Arg Phe Leu Arg Gln His Val His Pro Glu Glu Thr Gly Gly Ser Asp
20 25 30
Arg Tyr Cys Asn Leu Met Met Gln Arg Arg Lys Met Thr Leu Tyr His
35 40 45
Cys Lys Arg Phe Asn Thr Phe Ile His Glu Asp Ile Trp Asn Ile Arg
50 55 60
Ser Ile Cys Ser Thr Thr Asn Ile Gln Cys Lys Asn Gly Lys Met Asn
65 70 75 80
Cys His Glu Gly Val Val Lys Val Thr Asp Cys Arg Asp Thr Gly Ser
85 90 95
Ser Arg Ala Pro Asn Cys Arg Tyr Arg Ala Ile Ala Ser Thr Arg Arg
100 105 110
Val Val Ile Ala Cys Glu Gly Asn Pro Gln Val Pro Val His Phe Asp
115 120 125
Gly
<210> 141
<211> 375
<212> PRT
<213> 智人（Homo Sapiens）
<220>
<221> 尚未归类的特征
<222> (1)..(1)
<223> Xaa可以是任何天然存在的氨基酸
<400> 141
Xaa Ser Ala Val Asp Asn Ile Leu Leu Lys Leu Ala Lys Phe Lys Ile
1 5 10 15
Gly Phe Leu Arg Leu Gly Gln Ile Gln Lys Val His Pro Ala Ile Gln
20 25 30
Gln Phe Thr Glu Gln Glu Ile Cys Arg Ser Lys Ser Ile Lys Ser Leu
35 40 45
Ala Leu Leu Glu Glu Leu Tyr Asn Ser Gln Leu Ile Val Ala Thr Thr
50 55 60
Cys Met Gly Ile Asn His Pro Ile Phe Ser Arg Lys Ile Phe Asp Phe
65 70 75 80
Cys Ile Val Asp Glu Ala Ser Gln Ile Ser Gln Pro Ile Cys Leu Gly
85 90 95
Pro Leu Phe Phe Ser Arg Arg Phe Val Leu Val Gly Asp His Gln Gln
100 105 110
Leu Pro Pro Leu Val Leu Asn Arg Glu Ala Arg Ala Leu Gly Met Ser
115 120 125
Glu Ser Leu Phe Lys Arg Leu Glu Gln Asn Lys Ser Ala Val Val Gln
130 135 140
Leu Thr Val Gln Tyr Arg Met Asn Ser Lys Ile Met Ser Leu Ser Asn
145 150 155 160
Lys Leu Thr Tyr Glu Gly Lys Leu Glu Cys Gly Ser Asp Lys Val Ala
165 170 175
Asn Ala Val Ile Asn Leu Arg His Phe Lys Asp Val Lys Leu Glu Leu
180 185 190
Glu Phe Tyr Ala Asp Tyr Ser Asp Asn Pro Trp Leu Met Gly Val Phe
195 200 205
Glu Pro Asn Asn Pro Val Cys Phe Leu Asn Thr Asp Lys Val Pro Ala
210 215 220
Pro Glu Gln Val Glu Lys Gly Gly Val Ser Asn Val Thr Glu Ala Lys
225 230 235 240
Leu Ile Val Phe Leu Thr Ser Ile Phe Val Lys Ala Gly Cys Ser Pro
245 250 255
Ser Asp Ile Gly Ile Ile Ala Pro Tyr Arg Gln Gln Leu Lys Ile Ile
260 265 270
Asn Asp Leu Leu Ala Arg Ser Ile Gly Met Val Glu Val Asn Thr Val
275 280 285
Asp Lys Tyr Gln Gly Arg Asp Lys Ser Ile Val Leu Val Ser Phe Val
290 295 300
Arg Ser Asn Lys Asp Gly Thr Val Gly Glu Leu Leu Lys Asp Trp Arg
305 310 315 320
Arg Leu Asn Val Ala Ile Thr Arg Ala Lys His Lys Leu Ile Leu Leu
325 330 335
Gly Cys Val Pro Ser Leu Asn Cys Tyr Pro Pro Leu Glu Lys Leu Leu
340 345 350
Asn His Leu Asn Ser Glu Lys Leu Ile Ser Phe Phe Phe Cys Ile Trp
355 360 365
Ser His Leu Ile Ala Leu Leu
370 375
<210> 142
<211> 88
<212> PRT
<213> 智人（Homo Sapiens）
<400> 142
Met Ala Leu Arg Ser His Asp Arg Ser Thr Arg Pro Leu Tyr Ile Ser
1 5 10 15
Val Gly His Arg Met Ser Leu Glu Ala Ala Val Arg Leu Thr Cys Cys
20 25 30
Cys Cys Arg Phe Arg Ile Pro Glu Pro Val Arg Gln Ala Asp Ile Cys
35 40 45
Ser Arg Glu His Ile Arg Lys Ser Leu Gly Leu Pro Gly Pro Pro Thr
50 55 60
Pro Arg Ser Pro Lys Ala Gln Arg Pro Val Ala Cys Pro Lys Gly Asp
65 70 75 80
Ser Gly Glu Ser Ser Ala Leu Cys
85
<210> 143
<211> 212
<212> PRT
<213> 智人（Homo Sapiens）
<400> 143
Cys Tyr Thr Asn His Ala Leu Ser Tyr Asp Gln Ala Lys Arg Val Pro
1 5 10 15
Arg Trp Val Leu Glu His Ile Ser Lys Ser Lys Ile Met Gly Asp Ala
20 25 30
Asp Arg Lys His Cys Lys Phe Lys Pro Asp Pro Asn Ile Pro Pro Thr
35 40 45
Phe Ser Ala Phe Asn Glu Asp Tyr Val Gly Ser Gly Trp Ser Arg Gly
50 55 60
His Met Ala Pro Ala Gly Asn Asn Lys Phe Ser Ser Lys Ala Met Ala
65 70 75 80
Glu Thr Phe Tyr Leu Ser Asn Ile Val Pro Gln Asp Phe Asp Asn Asn
85 90 95
Ser Gly Tyr Trp Asn Arg Ile Glu Met Tyr Cys Arg Glu Leu Thr Glu
100 105 110
Arg Phe Glu Asp Val Trp Val Val Ser Gly Pro Leu Thr Leu Pro Gln
115 120 125
Thr Arg Gly Asp Gly Lys Lys Ile Val Ser Tyr Gln Val Ile Gly Glu
130 135 140
Asp Asn Val Ala Val Pro Ser His Leu Tyr Lys Val Ile Leu Ala Arg
145 150 155 160
Arg Ser Ser Val Ser Thr Glu Pro Leu Ala Leu Gly Ala Phe Val Val
165 170 175
Pro Asn Glu Ala Ile Gly Phe Gln Pro Gln Leu Thr Glu Phe Gln Val
180 185 190
Ser Leu Gln Asp Leu Glu Lys Leu Ser Gly Leu Val Phe Phe Pro His
195 200 205
Leu Asp Arg Thr
210
<210> 144
<211> 123
<212> PRT
<213> 智人（Homo Sapiens）
<400> 144
Val Thr Val Ser Gln Met Thr Ser Val Leu Asn Gly Lys Thr Arg Arg
1 5 10 15
Phe Ala Asp Ile Gln Leu Gln His Gly Ala Leu Cys Phe Asn Ile Arg
20 25 30
Tyr Gly Thr Thr Val Glu Glu Glu Lys Asn His Val Leu Glu Ile Ala
35 40 45
Arg Gln Arg Ala Val Ala Gln Ala Trp Thr Lys Glu Gln Arg Arg Leu
50 55 60
Gln Glu Gly Glu Glu Gly Ile Arg Ala Trp Thr Glu Gly Glu Lys Gln
65 70 75 80
Gln Leu Leu Ser Thr Gly Arg Val Gln Gly Tyr Asp Gly Tyr Phe Val
85 90 95
Leu Ser Val Glu Gln Tyr Leu Glu Leu Ser Asp Ser Ala Asn Asn Ile
100 105 110
His Phe Met Arg Gln Ser Glu Ile Gly Arg Arg
115 120
<210> 145
<211> 125
<212> PRT
<213> 智人（Homo Sapiens）
<400> 145
Thr Val Ser Gln Pro Thr Leu Leu Val Asn Gly Lys Thr Arg Arg Phe
1 5 10 15
Thr Asn Ile Glu Phe Gln Tyr Ser Thr Leu Leu Leu Ser Ile Arg Tyr
20 25 30
Gly Leu Thr Pro Asp Thr Leu Asp Glu Glu Lys Ala Arg Val Leu Asp
35 40 45
Gln Ala Arg Gln Arg Ala Leu Gly Thr Ala Trp Ala Lys Glu Gln Gln
50 55 60
Lys Ala Arg Asp Gly Arg Glu Gly Ser Arg Leu Trp Thr Glu Gly Glu
65 70 75 80
Lys Gln Gln Leu Leu Ser Thr Gly Arg Val Gln Gly Tyr Glu Gly Tyr
85 90 95
Tyr Val Leu Pro Val Glu Gln Tyr Pro Glu Leu Ala Asp Ser Ser Ser
100 105 110
Asn Ile Gln Phe Leu Arg Gln Asn Glu Met Gly Lys Arg
115 120 125
<210> 146
<400> 146
000
<210> 147
<211> 1368
<212> PRT
<213> 酿脓链球菌（Streptococcus pyogenes）
<400> 147
Met Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val
1 5 10 15
Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe
20 25 30
Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile
35 40 45
Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu
50 55 60
Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys
65 70 75 80
Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser
85 90 95
Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys
100 105 110
His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr
115 120 125
His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp
130 135 140
Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His
145 150 155 160
Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro
165 170 175
Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr
180 185 190
Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala
195 200 205
Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn
210 215 220
Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn
225 230 235 240
Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe
245 250 255
Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp
260 265 270
Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp
275 280 285
Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp
290 295 300
Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser
305 310 315 320
Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys
325 330 335
Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe
340 345 350
Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser
355 360 365
Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp
370 375 380
Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg
385 390 395 400
Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu
405 410 415
Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe
420 425 430
Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile
435 440 445
Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp
450 455 460
Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu
465 470 475 480
Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr
485 490 495
Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser
500 505 510
Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys
515 520 525
Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln
530 535 540
Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr
545 550 555 560
Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp
565 570 575
Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly
580 585 590
Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp
595 600 605
Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr
610 615 620
Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala
625 630 635 640
His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr
645 650 655
Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp
660 665 670
Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe
675 680 685
Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe
690 695 700
Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu
705 710 715 720
His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly
725 730 735
Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly
740 745 750
Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln
755 760 765
Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile
770 775 780
Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro
785 790 795 800
Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu
805 810 815
Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg
820 825 830
Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys
835 840 845
Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg
850 855 860
Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys
865 870 875 880
Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys
885 890 895
Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp
900 905 910
Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr
915 920 925
Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp
930 935 940
Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser
945 950 955 960
Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg
965 970 975
Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val
980 985 990
Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe
995 1000 1005
Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met Ile Ala
1010 1015 1020
Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe Phe
1025 1030 1035
Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala
1040 1045 1050
Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu
1055 1060 1065
Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala Thr Val
1070 1075 1080
Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr
1085 1090 1095
Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys
1100 1105 1110
Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro
1115 1120 1125
Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val
1130 1135 1140
Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys
1145 1150 1155
Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser
1160 1165 1170
Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys
1175 1180 1185
Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu
1190 1195 1200
Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly
1205 1210 1215
Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val
1220 1225 1230
Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser
1235 1240 1245
Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln His Lys
1250 1255 1260
His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser Lys
1265 1270 1275
Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala
1280 1285 1290
Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn
1295 1300 1305
Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala
1310 1315 1320
Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser
1325 1330 1335
Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr
1340 1345 1350
Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp
1355 1360 1365
<210> 148
<211> 1368
<212> PRT
<213> 酿脓链球菌（Streptococcus pyogenes）
<400> 148
Met Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly Thr Asn Ser Val
1 5 10 15
Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe
20 25 30
Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile
35 40 45
Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu
50 55 60
Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys
65 70 75 80
Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser
85 90 95
Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys
100 105 110
His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr
115 120 125
His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp
130 135 140
Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His
145 150 155 160
Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro
165 170 175
Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr
180 185 190
Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala
195 200 205
Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn
210 215 220
Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn
225 230 235 240
Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe
245 250 255
Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp
260 265 270
Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp
275 280 285
Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp
290 295 300
Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser
305 310 315 320
Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys
325 330 335
Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe
340 345 350
Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser
355 360 365
Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp
370 375 380
Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg
385 390 395 400
Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu
405 410 415
Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe
420 425 430
Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile
435 440 445
Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp
450 455 460
Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu
465 470 475 480
Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr
485 490 495
Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser
500 505 510
Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys
515 520 525
Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln
530 535 540
Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr
545 550 555 560
Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp
565 570 575
Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly
580 585 590
Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp
595 600 605
Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr
610 615 620
Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala
625 630 635 640
His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr
645 650 655
Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp
660 665 670
Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe
675 680 685
Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe
690 695 700
Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu
705 710 715 720
His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly
725 730 735
Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly
740 745 750
Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln
755 760 765
Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile
770 775 780
Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro
785 790 795 800
Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu
805 810 815
Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg
820 825 830
Leu Ser Asp Tyr Asp Val Asp Ala Ile Val Pro Gln Ser Phe Leu Lys
835 840 845
Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg
850 855 860
Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys
865 870 875 880
Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys
885 890 895
Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp
900 905 910
Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr
915 920 925
Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp
930 935 940
Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser
945 950 955 960
Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg
965 970 975
Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val
980 985 990
Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe
995 1000 1005
Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met Ile Ala
1010 1015 1020
Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe Phe
1025 1030 1035
Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala
1040 1045 1050
Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu
1055 1060 1065
Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala Thr Val
1070 1075 1080
Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr
1085 1090 1095
Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys
1100 1105 1110
Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro
1115 1120 1125
Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val
1130 1135 1140
Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys
1145 1150 1155
Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser
1160 1165 1170
Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys
1175 1180 1185
Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu
1190 1195 1200
Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly
1205 1210 1215
Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val
1220 1225 1230
Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser
1235 1240 1245
Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln His Lys
1250 1255 1260
His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser Lys
1265 1270 1275
Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala
1280 1285 1290
Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn
1295 1300 1305
Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala
1310 1315 1320
Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser
1325 1330 1335
Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr
1340 1345 1350
Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp
1355 1360 1365
<210> 149
<211> 1368
<212> PRT
<213> 酿脓链球菌（Streptococcus pyogenes）
<400> 149
Met Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val
1 5 10 15
Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe
20 25 30
Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile
35 40 45
Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu
50 55 60
Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys
65 70 75 80
Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser
85 90 95
Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys
100 105 110
His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr
115 120 125
His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp
130 135 140
Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His
145 150 155 160
Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro
165 170 175
Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr
180 185 190
Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala
195 200 205
Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn
210 215 220
Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn
225 230 235 240
Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe
245 250 255
Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp
260 265 270
Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp
275 280 285
Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp
290 295 300
Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser
305 310 315 320
Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys
325 330 335
Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe
340 345 350
Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser
355 360 365
Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp
370 375 380
Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg
385 390 395 400
Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu
405 410 415
Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe
420 425 430
Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile
435 440 445
Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp
450 455 460
Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu
465 470 475 480
Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr
485 490 495
Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser
500 505 510
Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys
515 520 525
Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln
530 535 540
Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr
545 550 555 560
Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp
565 570 575
Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly
580 585 590
Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp
595 600 605
Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr
610 615 620
Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala
625 630 635 640
His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr
645 650 655
Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp
660 665 670
Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe
675 680 685
Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe
690 695 700
Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu
705 710 715 720
His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly
725 730 735
Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly
740 745 750
Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln
755 760 765
Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile
770 775 780
Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro
785 790 795 800
Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu
805 810 815
Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg
820 825 830
Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys
835 840 845
Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg
850 855 860
Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys
865 870 875 880
Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys
885 890 895
Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp
900 905 910
Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr
915 920 925
Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp
930 935 940
Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser
945 950 955 960
Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg
965 970 975
Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val
980 985 990
Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe
995 1000 1005
Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met Ile Ala
1010 1015 1020
Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe Phe
1025 1030 1035
Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala
1040 1045 1050
Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu
1055 1060 1065
Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala Thr Val
1070 1075 1080
Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr
1085 1090 1095
Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys
1100 1105 1110
Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro
1115 1120 1125
Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val
1130 1135 1140
Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys
1145 1150 1155
Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser
1160 1165 1170
Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys
1175 1180 1185
Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu
1190 1195 1200
Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly
1205 1210 1215
Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val
1220 1225 1230
Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser
1235 1240 1245
Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln His Lys
1250 1255 1260
His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser Lys
1265 1270 1275
Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala
1280 1285 1290
Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn
1295 1300 1305
Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala
1310 1315 1320
Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser
1325 1330 1335
Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr
1340 1345 1350
Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp
1355 1360 1365
<210> 150
<211> 1053
<212> PRT
<213> 金黄色葡萄球菌（Staphylococcus aureus）
<400> 150
Met Lys Arg Asn Tyr Ile Leu Gly Leu Asp Ile Gly Ile Thr Ser Val
1 5 10 15
Gly Tyr Gly Ile Ile Asp Tyr Glu Thr Arg Asp Val Ile Asp Ala Gly
20 25 30
Val Arg Leu Phe Lys Glu Ala Asn Val Glu Asn Asn Glu Gly Arg Arg
35 40 45
Ser Lys Arg Gly Ala Arg Arg Leu Lys Arg Arg Arg Arg His Arg Ile
50 55 60
Gln Arg Val Lys Lys Leu Leu Phe Asp Tyr Asn Leu Leu Thr Asp His
65 70 75 80
Ser Glu Leu Ser Gly Ile Asn Pro Tyr Glu Ala Arg Val Lys Gly Leu
85 90 95
Ser Gln Lys Leu Ser Glu Glu Glu Phe Ser Ala Ala Leu Leu His Leu
100 105 110
Ala Lys Arg Arg Gly Val His Asn Val Asn Glu Val Glu Glu Asp Thr
115 120 125
Gly Asn Glu Leu Ser Thr Lys Glu Gln Ile Ser Arg Asn Ser Lys Ala
130 135 140
Leu Glu Glu Lys Tyr Val Ala Glu Leu Gln Leu Glu Arg Leu Lys Lys
145 150 155 160
Asp Gly Glu Val Arg Gly Ser Ile Asn Arg Phe Lys Thr Ser Asp Tyr
165 170 175
Val Lys Glu Ala Lys Gln Leu Leu Lys Val Gln Lys Ala Tyr His Gln
180 185 190
Leu Asp Gln Ser Phe Ile Asp Thr Tyr Ile Asp Leu Leu Glu Thr Arg
195 200 205
Arg Thr Tyr Tyr Glu Gly Pro Gly Glu Gly Ser Pro Phe Gly Trp Lys
210 215 220
Asp Ile Lys Glu Trp Tyr Glu Met Leu Met Gly His Cys Thr Tyr Phe
225 230 235 240
Pro Glu Glu Leu Arg Ser Val Lys Tyr Ala Tyr Asn Ala Asp Leu Tyr
245 250 255
Asn Ala Leu Asn Asp Leu Asn Asn Leu Val Ile Thr Arg Asp Glu Asn
260 265 270
Glu Lys Leu Glu Tyr Tyr Glu Lys Phe Gln Ile Ile Glu Asn Val Phe
275 280 285
Lys Gln Lys Lys Lys Pro Thr Leu Lys Gln Ile Ala Lys Glu Ile Leu
290 295 300
Val Asn Glu Glu Asp Ile Lys Gly Tyr Arg Val Thr Ser Thr Gly Lys
305 310 315 320
Pro Glu Phe Thr Asn Leu Lys Val Tyr His Asp Ile Lys Asp Ile Thr
325 330 335
Ala Arg Lys Glu Ile Ile Glu Asn Ala Glu Leu Leu Asp Gln Ile Ala
340 345 350
Lys Ile Leu Thr Ile Tyr Gln Ser Ser Glu Asp Ile Gln Glu Glu Leu
355 360 365
Thr Asn Leu Asn Ser Glu Leu Thr Gln Glu Glu Ile Glu Gln Ile Ser
370 375 380
Asn Leu Lys Gly Tyr Thr Gly Thr His Asn Leu Ser Leu Lys Ala Ile
385 390 395 400
Asn Leu Ile Leu Asp Glu Leu Trp His Thr Asn Asp Asn Gln Ile Ala
405 410 415
Ile Phe Asn Arg Leu Lys Leu Val Pro Lys Lys Val Asp Leu Ser Gln
420 425 430
Gln Lys Glu Ile Pro Thr Thr Leu Val Asp Asp Phe Ile Leu Ser Pro
435 440 445
Val Val Lys Arg Ser Phe Ile Gln Ser Ile Lys Val Ile Asn Ala Ile
450 455 460
Ile Lys Lys Tyr Gly Leu Pro Asn Asp Ile Ile Ile Glu Leu Ala Arg
465 470 475 480
Glu Lys Asn Ser Lys Asp Ala Gln Lys Met Ile Asn Glu Met Gln Lys
485 490 495
Arg Asn Arg Gln Thr Asn Glu Arg Ile Glu Glu Ile Ile Arg Thr Thr
500 505 510
Gly Lys Glu Asn Ala Lys Tyr Leu Ile Glu Lys Ile Lys Leu His Asp
515 520 525
Met Gln Glu Gly Lys Cys Leu Tyr Ser Leu Glu Ala Ile Pro Leu Glu
530 535 540
Asp Leu Leu Asn Asn Pro Phe Asn Tyr Glu Val Asp His Ile Ile Pro
545 550 555 560
Arg Ser Val Ser Phe Asp Asn Ser Phe Asn Asn Lys Val Leu Val Lys
565 570 575
Gln Glu Glu Asn Ser Lys Lys Gly Asn Arg Thr Pro Phe Gln Tyr Leu
580 585 590
Ser Ser Ser Asp Ser Lys Ile Ser Tyr Glu Thr Phe Lys Lys His Ile
595 600 605
Leu Asn Leu Ala Lys Gly Lys Gly Arg Ile Ser Lys Thr Lys Lys Glu
610 615 620
Tyr Leu Leu Glu Glu Arg Asp Ile Asn Arg Phe Ser Val Gln Lys Asp
625 630 635 640
Phe Ile Asn Arg Asn Leu Val Asp Thr Arg Tyr Ala Thr Arg Gly Leu
645 650 655
Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn Asn Leu Asp Val Lys
660 665 670
Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe Leu Arg Arg Lys Trp
675 680 685
Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys His His Ala Glu Asp
690 695 700
Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys
705 710 715 720
Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln Met Phe Glu Glu Lys
725 730 735
Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu
740 745 750
Ile Phe Ile Thr Pro His Gln Ile Lys His Ile Lys Asp Phe Lys Asp
755 760 765
Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro Asn Arg Glu Leu Ile
770 775 780
Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu
785 790 795 800
Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu
805 810 815
Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu Leu Met Tyr His His
820 825 830
Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly
835 840 845
Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr
850 855 860
Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro Val Ile Lys Lys Ile
865 870 875 880
Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu Asp Ile Thr Asp Asp
885 890 895
Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu Ser Leu Lys Pro Tyr
900 905 910
Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr Lys Phe Val Thr Val
915 920 925
Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser
930 935 940
Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala
945 950 955 960
Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly
965 970 975
Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp Leu Leu Asn Arg Ile
980 985 990
Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met
995 1000 1005
Asn Asp Lys Arg Pro Pro Arg Ile Ile Lys Thr Ile Ala Ser Lys
1010 1015 1020
Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu Gly Asn Leu
1025 1030 1035
Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys Lys Gly
1040 1045 1050
<210> 151
<211> 1121
<212> PRT
<213> 嗜热链球菌（Streptococcus thermophilus）
<400> 151
Met Ser Asp Leu Val Leu Gly Leu Asp Ile Gly Ile Gly Ser Val Gly
1 5 10 15
Val Gly Ile Leu Asn Lys Val Thr Gly Glu Ile Ile His Lys Asn Ser
20 25 30
Arg Ile Phe Pro Ala Ala Gln Ala Glu Asn Asn Leu Val Arg Arg Thr
35 40 45
Asn Arg Gln Gly Arg Arg Leu Ala Arg Arg Lys Lys His Arg Arg Val
50 55 60
Arg Leu Asn Arg Leu Phe Glu Glu Ser Gly Leu Ile Thr Asp Phe Thr
65 70 75 80
Lys Ile Ser Ile Asn Leu Asn Pro Tyr Gln Leu Arg Val Lys Gly Leu
85 90 95
Thr Asp Glu Leu Ser Asn Glu Glu Leu Phe Ile Ala Leu Lys Asn Met
100 105 110
Val Lys His Arg Gly Ile Ser Tyr Leu Asp Asp Ala Ser Asp Asp Gly
115 120 125
Asn Ser Ser Val Gly Asp Tyr Ala Gln Ile Val Lys Glu Asn Ser Lys
130 135 140
Gln Leu Glu Thr Lys Thr Pro Gly Gln Ile Gln Leu Glu Arg Tyr Gln
145 150 155 160
Thr Tyr Gly Gln Leu Arg Gly Asp Phe Thr Val Glu Lys Asp Gly Lys
165 170 175
Lys His Arg Leu Ile Asn Val Phe Pro Thr Ser Ala Tyr Arg Ser Glu
180 185 190
Ala Leu Arg Ile Leu Gln Thr Gln Gln Glu Phe Asn Pro Gln Ile Thr
195 200 205
Asp Glu Phe Ile Asn Arg Tyr Leu Glu Ile Leu Thr Gly Lys Arg Lys
210 215 220
Tyr Tyr His Gly Pro Gly Asn Glu Lys Ser Arg Thr Asp Tyr Gly Arg
225 230 235 240
Tyr Arg Thr Ser Gly Glu Thr Leu Asp Asn Ile Phe Gly Ile Leu Ile
245 250 255
Gly Lys Cys Thr Phe Tyr Pro Asp Glu Phe Arg Ala Ala Lys Ala Ser
260 265 270
Tyr Thr Ala Gln Glu Phe Asn Leu Leu Asn Asp Leu Asn Asn Leu Thr
275 280 285
Val Pro Thr Glu Thr Lys Lys Leu Ser Lys Glu Gln Lys Asn Gln Ile
290 295 300
Ile Asn Tyr Val Lys Asn Glu Lys Ala Met Gly Pro Ala Lys Leu Phe
305 310 315 320
Lys Tyr Ile Ala Lys Leu Leu Ser Cys Asp Val Ala Asp Ile Lys Gly
325 330 335
Tyr Arg Ile Asp Lys Ser Gly Lys Ala Glu Ile His Thr Phe Glu Ala
340 345 350
Tyr Arg Lys Met Lys Thr Leu Glu Thr Leu Asp Ile Glu Gln Met Asp
355 360 365
Arg Glu Thr Leu Asp Lys Leu Ala Tyr Val Leu Thr Leu Asn Thr Glu
370 375 380
Arg Glu Gly Ile Gln Glu Ala Leu Glu His Glu Phe Ala Asp Gly Ser
385 390 395 400
Phe Ser Gln Lys Gln Val Asp Glu Leu Val Gln Phe Arg Lys Ala Asn
405 410 415
Ser Ser Ile Phe Gly Lys Gly Trp His Asn Phe Ser Val Lys Leu Met
420 425 430
Met Glu Leu Ile Pro Glu Leu Tyr Glu Thr Ser Glu Glu Gln Met Thr
435 440 445
Ile Leu Thr Arg Leu Gly Lys Gln Lys Thr Thr Ser Ser Ser Asn Lys
450 455 460
Thr Lys Tyr Ile Asp Glu Lys Leu Leu Thr Glu Glu Ile Tyr Asn Pro
465 470 475 480
Val Val Ala Lys Ser Val Arg Gln Ala Ile Lys Ile Val Asn Ala Ala
485 490 495
Ile Lys Glu Tyr Gly Asp Phe Asp Asn Ile Val Ile Glu Met Ala Arg
500 505 510
Glu Thr Asn Glu Asp Asp Glu Lys Lys Ala Ile Gln Lys Ile Gln Lys
515 520 525
Ala Asn Lys Asp Glu Lys Asp Ala Ala Met Leu Lys Ala Ala Asn Gln
530 535 540
Tyr Asn Gly Lys Ala Glu Leu Pro His Ser Val Phe His Gly His Lys
545 550 555 560
Gln Leu Ala Thr Lys Ile Arg Leu Trp His Gln Gln Gly Glu Arg Cys
565 570 575
Leu Tyr Thr Gly Lys Thr Ile Ser Ile His Asp Leu Ile Asn Asn Ser
580 585 590
Asn Gln Phe Glu Val Asp His Ile Leu Pro Leu Ser Ile Thr Phe Asp
595 600 605
Asp Ser Leu Ala Asn Lys Val Leu Val Tyr Ala Thr Ala Asn Gln Glu
610 615 620
Lys Gly Gln Arg Thr Pro Tyr Gln Ala Leu Asp Ser Met Asp Asp Ala
625 630 635 640
Trp Ser Phe Arg Glu Leu Lys Ala Phe Val Arg Glu Ser Lys Thr Leu
645 650 655
Ser Asn Lys Lys Lys Glu Tyr Leu Leu Thr Glu Glu Asp Ile Ser Lys
660 665 670
Phe Asp Val Arg Lys Lys Phe Ile Glu Arg Asn Leu Val Asp Thr Arg
675 680 685
Tyr Ala Ser Arg Val Val Leu Asn Ala Leu Gln Glu His Phe Arg Ala
690 695 700
His Lys Ile Asp Thr Lys Val Ser Val Val Arg Gly Gln Phe Thr Ser
705 710 715 720
Gln Leu Arg Arg His Trp Gly Ile Glu Lys Thr Arg Asp Thr Tyr His
725 730 735
His His Ala Val Asp Ala Leu Ile Ile Ala Ala Ser Ser Gln Leu Asn
740 745 750
Leu Trp Lys Lys Gln Lys Asn Thr Leu Val Ser Tyr Ser Glu Asp Gln
755 760 765
Leu Leu Asp Ile Glu Thr Gly Glu Leu Ile Ser Asp Asp Glu Tyr Lys
770 775 780
Glu Ser Val Phe Lys Ala Pro Tyr Gln His Phe Val Asp Thr Leu Lys
785 790 795 800
Ser Lys Glu Phe Glu Asp Ser Ile Leu Phe Ser Tyr Gln Val Asp Ser
805 810 815
Lys Phe Asn Arg Lys Ile Ser Asp Ala Thr Ile Tyr Ala Thr Arg Gln
820 825 830
Ala Lys Val Gly Lys Asp Lys Ala Asp Glu Thr Tyr Val Leu Gly Lys
835 840 845
Ile Lys Asp Ile Tyr Thr Gln Asp Gly Tyr Asp Ala Phe Met Lys Ile
850 855 860
Tyr Lys Lys Asp Lys Ser Lys Phe Leu Met Tyr Arg His Asp Pro Gln
865 870 875 880
Thr Phe Glu Lys Val Ile Glu Pro Ile Leu Glu Asn Tyr Pro Asn Lys
885 890 895
Gln Ile Asn Asp Lys Gly Lys Glu Val Pro Cys Asn Pro Phe Leu Lys
900 905 910
Tyr Lys Glu Glu His Gly Tyr Ile Arg Lys Tyr Ser Lys Lys Gly Asn
915 920 925
Gly Pro Glu Ile Lys Ser Leu Lys Tyr Tyr Asp Ser Lys Leu Gly Asn
930 935 940
His Ile Asp Ile Thr Pro Lys Asp Ser Asn Asn Lys Val Val Leu Gln
945 950 955 960
Ser Val Ser Pro Trp Arg Ala Asp Val Tyr Phe Asn Lys Thr Thr Gly
965 970 975
Lys Tyr Glu Ile Leu Gly Leu Lys Tyr Ala Asp Leu Gln Phe Asp Lys
980 985 990
Gly Thr Gly Thr Tyr Lys Ile Ser Gln Glu Lys Tyr Asn Asp Ile Lys
995 1000 1005
Lys Lys Glu Gly Val Asp Ser Asp Ser Glu Phe Lys Phe Thr Leu
1010 1015 1020
Tyr Lys Asn Asp Leu Leu Leu Val Lys Asp Thr Glu Thr Lys Glu
1025 1030 1035
Gln Gln Leu Phe Arg Phe Leu Ser Arg Thr Met Pro Lys Gln Lys
1040 1045 1050
His Tyr Val Glu Leu Lys Pro Tyr Asp Lys Gln Lys Phe Glu Gly
1055 1060 1065
Gly Glu Ala Leu Ile Lys Val Leu Gly Asn Val Ala Asn Ser Gly
1070 1075 1080
Gln Cys Lys Lys Gly Leu Gly Lys Ser Asn Ile Ser Ile Tyr Lys
1085 1090 1095
Val Arg Thr Asp Val Leu Gly Asn Gln His Ile Ile Lys Asn Glu
1100 1105 1110
Gly Asp Lys Pro Lys Leu Asp Phe
1115 1120
<210> 152
<211> 1082
<212> PRT
<213> 脑膜炎奈瑟球菌（Neisseria meningitidis）
<400> 152
Met Ala Ala Phe Lys Pro Asn Pro Ile Asn Tyr Ile Leu Gly Leu Asp
1 5 10 15
Ile Gly Ile Ala Ser Val Gly Trp Ala Met Val Glu Ile Asp Glu Asp
20 25 30
Glu Asn Pro Ile Cys Leu Ile Asp Leu Gly Val Arg Val Phe Glu Arg
35 40 45
Ala Glu Val Pro Lys Thr Gly Asp Ser Leu Ala Met Ala Arg Arg Leu
50 55 60
Ala Arg Ser Val Arg Arg Leu Thr Arg Arg Arg Ala His Arg Leu Leu
65 70 75 80
Arg Ala Arg Arg Leu Leu Lys Arg Glu Gly Val Leu Gln Ala Ala Asp
85 90 95
Phe Asp Glu Asn Gly Leu Ile Lys Ser Leu Pro Asn Thr Pro Trp Gln
100 105 110
Leu Arg Ala Ala Ala Leu Asp Arg Lys Leu Thr Pro Leu Glu Trp Ser
115 120 125
Ala Val Leu Leu His Leu Ile Lys His Arg Gly Tyr Leu Ser Gln Arg
130 135 140
Lys Asn Glu Gly Glu Thr Ala Asp Lys Glu Leu Gly Ala Leu Leu Lys
145 150 155 160
Gly Val Ala Asp Asn Ala His Ala Leu Gln Thr Gly Asp Phe Arg Thr
165 170 175
Pro Ala Glu Leu Ala Leu Asn Lys Phe Glu Lys Glu Ser Gly His Ile
180 185 190
Arg Asn Gln Arg Gly Asp Tyr Ser His Thr Phe Ser Arg Lys Asp Leu
195 200 205
Gln Ala Glu Leu Ile Leu Leu Phe Glu Lys Gln Lys Glu Phe Gly Asn
210 215 220
Pro His Val Ser Gly Gly Leu Lys Glu Gly Ile Glu Thr Leu Leu Met
225 230 235 240
Thr Gln Arg Pro Ala Leu Ser Gly Asp Ala Val Gln Lys Met Leu Gly
245 250 255
His Cys Thr Phe Glu Pro Ala Glu Pro Lys Ala Ala Lys Asn Thr Tyr
260 265 270
Thr Ala Glu Arg Phe Ile Trp Leu Thr Lys Leu Asn Asn Leu Arg Ile
275 280 285
Leu Glu Gln Gly Ser Glu Arg Pro Leu Thr Asp Thr Glu Arg Ala Thr
290 295 300
Leu Met Asp Glu Pro Tyr Arg Lys Ser Lys Leu Thr Tyr Ala Gln Ala
305 310 315 320
Arg Lys Leu Leu Gly Leu Glu Asp Thr Ala Phe Phe Lys Gly Leu Arg
325 330 335
Tyr Gly Lys Asp Asn Ala Glu Ala Ser Thr Leu Met Glu Met Lys Ala
340 345 350
Tyr His Ala Ile Ser Arg Ala Leu Glu Lys Glu Gly Leu Lys Asp Lys
355 360 365
Lys Ser Pro Leu Asn Leu Ser Pro Glu Leu Gln Asp Glu Ile Gly Thr
370 375 380
Ala Phe Ser Leu Phe Lys Thr Asp Glu Asp Ile Thr Gly Arg Leu Lys
385 390 395 400
Asp Arg Ile Gln Pro Glu Ile Leu Glu Ala Leu Leu Lys His Ile Ser
405 410 415
Phe Asp Lys Phe Val Gln Ile Ser Leu Lys Ala Leu Arg Arg Ile Val
420 425 430
Pro Leu Met Glu Gln Gly Lys Arg Tyr Asp Glu Ala Cys Ala Glu Ile
435 440 445
Tyr Gly Asp His Tyr Gly Lys Lys Asn Thr Glu Glu Lys Ile Tyr Leu
450 455 460
Pro Pro Ile Pro Ala Asp Glu Ile Arg Asn Pro Val Val Leu Arg Ala
465 470 475 480
Leu Ser Gln Ala Arg Lys Val Ile Asn Gly Val Val Arg Arg Tyr Gly
485 490 495
Ser Pro Ala Arg Ile His Ile Glu Thr Ala Arg Glu Val Gly Lys Ser
500 505 510
Phe Lys Asp Arg Lys Glu Ile Glu Lys Arg Gln Glu Glu Asn Arg Lys
515 520 525
Asp Arg Glu Lys Ala Ala Ala Lys Phe Arg Glu Tyr Phe Pro Asn Phe
530 535 540
Val Gly Glu Pro Lys Ser Lys Asp Ile Leu Lys Leu Arg Leu Tyr Glu
545 550 555 560
Gln Gln His Gly Lys Cys Leu Tyr Ser Gly Lys Glu Ile Asn Leu Gly
565 570 575
Arg Leu Asn Glu Lys Gly Tyr Val Glu Ile Asp His Ala Leu Pro Phe
580 585 590
Ser Arg Thr Trp Asp Asp Ser Phe Asn Asn Lys Val Leu Val Leu Gly
595 600 605
Ser Glu Asn Gln Asn Lys Gly Asn Gln Thr Pro Tyr Glu Tyr Phe Asn
610 615 620
Gly Lys Asp Asn Ser Arg Glu Trp Gln Glu Phe Lys Ala Arg Val Glu
625 630 635 640
Thr Ser Arg Phe Pro Arg Ser Lys Lys Gln Arg Ile Leu Leu Gln Lys
645 650 655
Phe Asp Glu Asp Gly Phe Lys Glu Arg Asn Leu Asn Asp Thr Arg Tyr
660 665 670
Val Asn Arg Phe Leu Cys Gln Phe Val Ala Asp Arg Met Arg Leu Thr
675 680 685
Gly Lys Gly Lys Lys Arg Val Phe Ala Ser Asn Gly Gln Ile Thr Asn
690 695 700
Leu Leu Arg Gly Phe Trp Gly Leu Arg Lys Val Arg Ala Glu Asn Asp
705 710 715 720
Arg His His Ala Leu Asp Ala Val Val Val Ala Cys Ser Thr Val Ala
725 730 735
Met Gln Gln Lys Ile Thr Arg Phe Val Arg Tyr Lys Glu Met Asn Ala
740 745 750
Phe Asp Gly Lys Thr Ile Asp Lys Glu Thr Gly Glu Val Leu His Gln
755 760 765
Lys Thr His Phe Pro Gln Pro Trp Glu Phe Phe Ala Gln Glu Val Met
770 775 780
Ile Arg Val Phe Gly Lys Pro Asp Gly Lys Pro Glu Phe Glu Glu Ala
785 790 795 800
Asp Thr Pro Glu Lys Leu Arg Thr Leu Leu Ala Glu Lys Leu Ser Ser
805 810 815
Arg Pro Glu Ala Val His Glu Tyr Val Thr Pro Leu Phe Val Ser Arg
820 825 830
Ala Pro Asn Arg Lys Met Ser Gly Gln Gly His Met Glu Thr Val Lys
835 840 845
Ser Ala Lys Arg Leu Asp Glu Gly Val Ser Val Leu Arg Val Pro Leu
850 855 860
Thr Gln Leu Lys Leu Lys Asp Leu Glu Lys Met Val Asn Arg Glu Arg
865 870 875 880
Glu Pro Lys Leu Tyr Glu Ala Leu Lys Ala Arg Leu Glu Ala His Lys
885 890 895
Asp Asp Pro Ala Lys Ala Phe Ala Glu Pro Phe Tyr Lys Tyr Asp Lys
900 905 910
Ala Gly Asn Arg Thr Gln Gln Val Lys Ala Val Arg Val Glu Gln Val
915 920 925
Gln Lys Thr Gly Val Trp Val Arg Asn His Asn Gly Ile Ala Asp Asn
930 935 940
Ala Thr Met Val Arg Val Asp Val Phe Glu Lys Gly Asp Lys Tyr Tyr
945 950 955 960
Leu Val Pro Ile Tyr Ser Trp Gln Val Ala Lys Gly Ile Leu Pro Asp
965 970 975
Arg Ala Val Val Gln Gly Lys Asp Glu Glu Asp Trp Gln Leu Ile Asp
980 985 990
Asp Ser Phe Asn Phe Lys Phe Ser Leu His Pro Asn Asp Leu Val Glu
995 1000 1005
Val Ile Thr Lys Lys Ala Arg Met Phe Gly Tyr Phe Ala Ser Cys
1010 1015 1020
His Arg Gly Thr Gly Asn Ile Asn Ile Arg Ile His Asp Leu Asp
1025 1030 1035
His Lys Ile Gly Lys Asn Gly Ile Leu Glu Gly Ile Gly Val Lys
1040 1045 1050
Thr Ala Leu Ser Phe Gln Lys Tyr Gln Ile Asp Glu Leu Gly Lys
1055 1060 1065
Glu Ile Arg Pro Cys Arg Leu Lys Lys Arg Pro Pro Val Arg
1070 1075 1080
<210> 153
<211> 1037
<212> PRT
<213> 食清洁剂细小棒菌（Parvibaculum lavamentivorans）
<400> 153
Met Glu Arg Ile Phe Gly Phe Asp Ile Gly Thr Thr Ser Ile Gly Phe
1 5 10 15
Ser Val Ile Asp Tyr Ser Ser Thr Gln Ser Ala Gly Asn Ile Gln Arg
20 25 30
Leu Gly Val Arg Ile Phe Pro Glu Ala Arg Asp Pro Asp Gly Thr Pro
35 40 45
Leu Asn Gln Gln Arg Arg Gln Lys Arg Met Met Arg Arg Gln Leu Arg
50 55 60
Arg Arg Arg Ile Arg Arg Lys Ala Leu Asn Glu Thr Leu His Glu Ala
65 70 75 80
Gly Phe Leu Pro Ala Tyr Gly Ser Ala Asp Trp Pro Val Val Met Ala
85 90 95
Asp Glu Pro Tyr Glu Leu Arg Arg Arg Gly Leu Glu Glu Gly Leu Ser
100 105 110
Ala Tyr Glu Phe Gly Arg Ala Ile Tyr His Leu Ala Gln His Arg His
115 120 125
Phe Lys Gly Arg Glu Leu Glu Glu Ser Asp Thr Pro Asp Pro Asp Val
130 135 140
Asp Asp Glu Lys Glu Ala Ala Asn Glu Arg Ala Ala Thr Leu Lys Ala
145 150 155 160
Leu Lys Asn Glu Gln Thr Thr Leu Gly Ala Trp Leu Ala Arg Arg Pro
165 170 175
Pro Ser Asp Arg Lys Arg Gly Ile His Ala His Arg Asn Val Val Ala
180 185 190
Glu Glu Phe Glu Arg Leu Trp Glu Val Gln Ser Lys Phe His Pro Ala
195 200 205
Leu Lys Ser Glu Glu Met Arg Ala Arg Ile Ser Asp Thr Ile Phe Ala
210 215 220
Gln Arg Pro Val Phe Trp Arg Lys Asn Thr Leu Gly Glu Cys Arg Phe
225 230 235 240
Met Pro Gly Glu Pro Leu Cys Pro Lys Gly Ser Trp Leu Ser Gln Gln
245 250 255
Arg Arg Met Leu Glu Lys Leu Asn Asn Leu Ala Ile Ala Gly Gly Asn
260 265 270
Ala Arg Pro Leu Asp Ala Glu Glu Arg Asp Ala Ile Leu Ser Lys Leu
275 280 285
Gln Gln Gln Ala Ser Met Ser Trp Pro Gly Val Arg Ser Ala Leu Lys
290 295 300
Ala Leu Tyr Lys Gln Arg Gly Glu Pro Gly Ala Glu Lys Ser Leu Lys
305 310 315 320
Phe Asn Leu Glu Leu Gly Gly Glu Ser Lys Leu Leu Gly Asn Ala Leu
325 330 335
Glu Ala Lys Leu Ala Asp Met Phe Gly Pro Asp Trp Pro Ala His Pro
340 345 350
Arg Lys Gln Glu Ile Arg His Ala Val His Glu Arg Leu Trp Ala Ala
355 360 365
Asp Tyr Gly Glu Thr Pro Asp Lys Lys Arg Val Ile Ile Leu Ser Glu
370 375 380
Lys Asp Arg Lys Ala His Arg Glu Ala Ala Ala Asn Ser Phe Val Ala
385 390 395 400
Asp Phe Gly Ile Thr Gly Glu Gln Ala Ala Gln Leu Gln Ala Leu Lys
405 410 415
Leu Pro Thr Gly Trp Glu Pro Tyr Ser Ile Pro Ala Leu Asn Leu Phe
420 425 430
Leu Ala Glu Leu Glu Lys Gly Glu Arg Phe Gly Ala Leu Val Asn Gly
435 440 445
Pro Asp Trp Glu Gly Trp Arg Arg Thr Asn Phe Pro His Arg Asn Gln
450 455 460
Pro Thr Gly Glu Ile Leu Asp Lys Leu Pro Ser Pro Ala Ser Lys Glu
465 470 475 480
Glu Arg Glu Arg Ile Ser Gln Leu Arg Asn Pro Thr Val Val Arg Thr
485 490 495
Gln Asn Glu Leu Arg Lys Val Val Asn Asn Leu Ile Gly Leu Tyr Gly
500 505 510
Lys Pro Asp Arg Ile Arg Ile Glu Val Gly Arg Asp Val Gly Lys Ser
515 520 525
Lys Arg Glu Arg Glu Glu Ile Gln Ser Gly Ile Arg Arg Asn Glu Lys
530 535 540
Gln Arg Lys Lys Ala Thr Glu Asp Leu Ile Lys Asn Gly Ile Ala Asn
545 550 555 560
Pro Ser Arg Asp Asp Val Glu Lys Trp Ile Leu Trp Lys Glu Gly Gln
565 570 575
Glu Arg Cys Pro Tyr Thr Gly Asp Gln Ile Gly Phe Asn Ala Leu Phe
580 585 590
Arg Glu Gly Arg Tyr Glu Val Glu His Ile Trp Pro Arg Ser Arg Ser
595 600 605
Phe Asp Asn Ser Pro Arg Asn Lys Thr Leu Cys Arg Lys Asp Val Asn
610 615 620
Ile Glu Lys Gly Asn Arg Met Pro Phe Glu Ala Phe Gly His Asp Glu
625 630 635 640
Asp Arg Trp Ser Ala Ile Gln Ile Arg Leu Gln Gly Met Val Ser Ala
645 650 655
Lys Gly Gly Thr Gly Met Ser Pro Gly Lys Val Lys Arg Phe Leu Ala
660 665 670
Lys Thr Met Pro Glu Asp Phe Ala Ala Arg Gln Leu Asn Asp Thr Arg
675 680 685
Tyr Ala Ala Lys Gln Ile Leu Ala Gln Leu Lys Arg Leu Trp Pro Asp
690 695 700
Met Gly Pro Glu Ala Pro Val Lys Val Glu Ala Val Thr Gly Gln Val
705 710 715 720
Thr Ala Gln Leu Arg Lys Leu Trp Thr Leu Asn Asn Ile Leu Ala Asp
725 730 735
Asp Gly Glu Lys Thr Arg Ala Asp His Arg His His Ala Ile Asp Ala
740 745 750
Leu Thr Val Ala Cys Thr His Pro Gly Met Thr Asn Lys Leu Ser Arg
755 760 765
Tyr Trp Gln Leu Arg Asp Asp Pro Arg Ala Glu Lys Pro Ala Leu Thr
770 775 780
Pro Pro Trp Asp Thr Ile Arg Ala Asp Ala Glu Lys Ala Val Ser Glu
785 790 795 800
Ile Val Val Ser His Arg Val Arg Lys Lys Val Ser Gly Pro Leu His
805 810 815
Lys Glu Thr Thr Tyr Gly Asp Thr Gly Thr Asp Ile Lys Thr Lys Ser
820 825 830
Gly Thr Tyr Arg Gln Phe Val Thr Arg Lys Lys Ile Glu Ser Leu Ser
835 840 845
Lys Gly Glu Leu Asp Glu Ile Arg Asp Pro Arg Ile Lys Glu Ile Val
850 855 860
Ala Ala His Val Ala Gly Arg Gly Gly Asp Pro Lys Lys Ala Phe Pro
865 870 875 880
Pro Tyr Pro Cys Val Ser Pro Gly Gly Pro Glu Ile Arg Lys Val Arg
885 890 895
Leu Thr Ser Lys Gln Gln Leu Asn Leu Met Ala Gln Thr Gly Asn Gly
900 905 910
Tyr Ala Asp Leu Gly Ser Asn His His Ile Ala Ile Tyr Arg Leu Pro
915 920 925
Asp Gly Lys Ala Asp Phe Glu Ile Val Ser Leu Phe Asp Ala Ser Arg
930 935 940
Arg Leu Ala Gln Arg Asn Pro Ile Val Gln Arg Thr Arg Ala Asp Gly
945 950 955 960
Ala Ser Phe Val Met Ser Leu Ala Ala Gly Glu Ala Ile Met Ile Pro
965 970 975
Glu Gly Ser Lys Lys Gly Ile Trp Ile Val Gln Gly Val Trp Ala Ser
980 985 990
Gly Gln Val Val Leu Glu Arg Asp Thr Asp Ala Asp His Ser Thr Thr
995 1000 1005
Thr Arg Pro Met Pro Asn Pro Ile Leu Lys Asp Asp Ala Lys Lys
1010 1015 1020
Val Ser Ile Asp Pro Ile Gly Arg Val Arg Pro Ser Asn Asp
1025 1030 1035
<210> 154
<211> 1084
<212> PRT
<213> 白喉棒状杆菌（Corynebacter diphtheria）
<400> 154
Met Lys Tyr His Val Gly Ile Asp Val Gly Thr Phe Ser Val Gly Leu
1 5 10 15
Ala Ala Ile Glu Val Asp Asp Ala Gly Met Pro Ile Lys Thr Leu Ser
20 25 30
Leu Val Ser His Ile His Asp Ser Gly Leu Asp Pro Asp Glu Ile Lys
35 40 45
Ser Ala Val Thr Arg Leu Ala Ser Ser Gly Ile Ala Arg Arg Thr Arg
50 55 60
Arg Leu Tyr Arg Arg Lys Arg Arg Arg Leu Gln Gln Leu Asp Lys Phe
65 70 75 80
Ile Gln Arg Gln Gly Trp Pro Val Ile Glu Leu Glu Asp Tyr Ser Asp
85 90 95
Pro Leu Tyr Pro Trp Lys Val Arg Ala Glu Leu Ala Ala Ser Tyr Ile
100 105 110
Ala Asp Glu Lys Glu Arg Gly Glu Lys Leu Ser Val Ala Leu Arg His
115 120 125
Ile Ala Arg His Arg Gly Trp Arg Asn Pro Tyr Ala Lys Val Ser Ser
130 135 140
Leu Tyr Leu Pro Asp Gly Pro Ser Asp Ala Phe Lys Ala Ile Arg Glu
145 150 155 160
Glu Ile Lys Arg Ala Ser Gly Gln Pro Val Pro Glu Thr Ala Thr Val
165 170 175
Gly Gln Met Val Thr Leu Cys Glu Leu Gly Thr Leu Lys Leu Arg Gly
180 185 190
Glu Gly Gly Val Leu Ser Ala Arg Leu Gln Gln Ser Asp Tyr Ala Arg
195 200 205
Glu Ile Gln Glu Ile Cys Arg Met Gln Glu Ile Gly Gln Glu Leu Tyr
210 215 220
Arg Lys Ile Ile Asp Val Val Phe Ala Ala Glu Ser Pro Lys Gly Ser
225 230 235 240
Ala Ser Ser Arg Val Gly Lys Asp Pro Leu Gln Pro Gly Lys Asn Arg
245 250 255
Ala Leu Lys Ala Ser Asp Ala Phe Gln Arg Tyr Arg Ile Ala Ala Leu
260 265 270
Ile Gly Asn Leu Arg Val Arg Val Asp Gly Glu Lys Arg Ile Leu Ser
275 280 285
Val Glu Glu Lys Asn Leu Val Phe Asp His Leu Val Asn Leu Thr Pro
290 295 300
Lys Lys Glu Pro Glu Trp Val Thr Ile Ala Glu Ile Leu Gly Ile Asp
305 310 315 320
Arg Gly Gln Leu Ile Gly Thr Ala Thr Met Thr Asp Asp Gly Glu Arg
325 330 335
Ala Gly Ala Arg Pro Pro Thr His Asp Thr Asn Arg Ser Ile Val Asn
340 345 350
Ser Arg Ile Ala Pro Leu Val Asp Trp Trp Lys Thr Ala Ser Ala Leu
355 360 365
Glu Gln His Ala Met Val Lys Ala Leu Ser Asn Ala Glu Val Asp Asp
370 375 380
Phe Asp Ser Pro Glu Gly Ala Lys Val Gln Ala Phe Phe Ala Asp Leu
385 390 395 400
Asp Asp Asp Val His Ala Lys Leu Asp Ser Leu His Leu Pro Val Gly
405 410 415
Arg Ala Ala Tyr Ser Glu Asp Thr Leu Val Arg Leu Thr Arg Arg Met
420 425 430
Leu Ser Asp Gly Val Asp Leu Tyr Thr Ala Arg Leu Gln Glu Phe Gly
435 440 445
Ile Glu Pro Ser Trp Thr Pro Pro Thr Pro Arg Ile Gly Glu Pro Val
450 455 460
Gly Asn Pro Ala Val Asp Arg Val Leu Lys Thr Val Ser Arg Trp Leu
465 470 475 480
Glu Ser Ala Thr Lys Thr Trp Gly Ala Pro Glu Arg Val Ile Ile Glu
485 490 495
His Val Arg Glu Gly Phe Val Thr Glu Lys Arg Ala Arg Glu Met Asp
500 505 510
Gly Asp Met Arg Arg Arg Ala Ala Arg Asn Ala Lys Leu Phe Gln Glu
515 520 525
Met Gln Glu Lys Leu Asn Val Gln Gly Lys Pro Ser Arg Ala Asp Leu
530 535 540
Trp Arg Tyr Gln Ser Val Gln Arg Gln Asn Cys Gln Cys Ala Tyr Cys
545 550 555 560
Gly Ser Pro Ile Thr Phe Ser Asn Ser Glu Met Asp His Ile Val Pro
565 570 575
Arg Ala Gly Gln Gly Ser Thr Asn Thr Arg Glu Asn Leu Val Ala Val
580 585 590
Cys His Arg Cys Asn Gln Ser Lys Gly Asn Thr Pro Phe Ala Ile Trp
595 600 605
Ala Lys Asn Thr Ser Ile Glu Gly Val Ser Val Lys Glu Ala Val Glu
610 615 620
Arg Thr Arg His Trp Val Thr Asp Thr Gly Met Arg Ser Thr Asp Phe
625 630 635 640
Lys Lys Phe Thr Lys Ala Val Val Glu Arg Phe Gln Arg Ala Thr Met
645 650 655
Asp Glu Glu Ile Asp Ala Arg Ser Met Glu Ser Val Ala Trp Met Ala
660 665 670
Asn Glu Leu Arg Ser Arg Val Ala Gln His Phe Ala Ser His Gly Thr
675 680 685
Thr Val Arg Val Tyr Arg Gly Ser Leu Thr Ala Glu Ala Arg Arg Ala
690 695 700
Ser Gly Ile Ser Gly Lys Leu Lys Phe Phe Asp Gly Val Gly Lys Ser
705 710 715 720
Arg Leu Asp Arg Arg His His Ala Ile Asp Ala Ala Val Ile Ala Phe
725 730 735
Thr Ser Asp Tyr Val Ala Glu Thr Leu Ala Val Arg Ser Asn Leu Lys
740 745 750
Gln Ser Gln Ala His Arg Gln Glu Ala Pro Gln Trp Arg Glu Phe Thr
755 760 765
Gly Lys Asp Ala Glu His Arg Ala Ala Trp Arg Val Trp Cys Gln Lys
770 775 780
Met Glu Lys Leu Ser Ala Leu Leu Thr Glu Asp Leu Arg Asp Asp Arg
785 790 795 800
Val Val Val Met Ser Asn Val Arg Leu Arg Leu Gly Asn Gly Ser Ala
805 810 815
His Lys Glu Thr Ile Gly Lys Leu Ser Lys Val Lys Leu Ser Ser Gln
820 825 830
Leu Ser Val Ser Asp Ile Asp Lys Ala Ser Ser Glu Ala Leu Trp Cys
835 840 845
Ala Leu Thr Arg Glu Pro Gly Phe Asp Pro Lys Glu Gly Leu Pro Ala
850 855 860
Asn Pro Glu Arg His Ile Arg Val Asn Gly Thr His Val Tyr Ala Gly
865 870 875 880
Asp Asn Ile Gly Leu Phe Pro Val Ser Ala Gly Ser Ile Ala Leu Arg
885 890 895
Gly Gly Tyr Ala Glu Leu Gly Ser Ser Phe His His Ala Arg Val Tyr
900 905 910
Lys Ile Thr Ser Gly Lys Lys Pro Ala Phe Ala Met Leu Arg Val Tyr
915 920 925
Thr Ile Asp Leu Leu Pro Tyr Arg Asn Gln Asp Leu Phe Ser Val Glu
930 935 940
Leu Lys Pro Gln Thr Met Ser Met Arg Gln Ala Glu Lys Lys Leu Arg
945 950 955 960
Asp Ala Leu Ala Thr Gly Asn Ala Glu Tyr Leu Gly Trp Leu Val Val
965 970 975
Asp Asp Glu Leu Val Val Asp Thr Ser Lys Ile Ala Thr Asp Gln Val
980 985 990
Lys Ala Val Glu Ala Glu Leu Gly Thr Ile Arg Arg Trp Arg Val Asp
995 1000 1005
Gly Phe Phe Ser Pro Ser Lys Leu Arg Leu Arg Pro Leu Gln Met
1010 1015 1020
Ser Lys Glu Gly Ile Lys Lys Glu Ser Ala Pro Glu Leu Ser Lys
1025 1030 1035
Ile Ile Asp Arg Pro Gly Trp Leu Pro Ala Val Asn Lys Leu Phe
1040 1045 1050
Ser Asp Gly Asn Val Thr Val Val Arg Arg Asp Ser Leu Gly Arg
1055 1060 1065
Val Arg Leu Glu Ser Thr Ala His Leu Pro Val Thr Trp Lys Val
1070 1075 1080
Gln
<210> 155
<211> 1130
<212> PRT
<213> 巴氏链球菌（Streptococcus pasteurianus）
<400> 155
Met Thr Asn Gly Lys Ile Leu Gly Leu Asp Ile Gly Ile Ala Ser Val
1 5 10 15
Gly Val Gly Ile Ile Glu Ala Lys Thr Gly Lys Val Val His Ala Asn
20 25 30
Ser Arg Leu Phe Ser Ala Ala Asn Ala Glu Asn Asn Ala Glu Arg Arg
35 40 45
Gly Phe Arg Gly Ser Arg Arg Leu Asn Arg Arg Lys Lys His Arg Val
50 55 60
Lys Arg Val Arg Asp Leu Phe Glu Lys Tyr Gly Ile Val Thr Asp Phe
65 70 75 80
Arg Asn Leu Asn Leu Asn Pro Tyr Glu Leu Arg Val Lys Gly Leu Thr
85 90 95
Glu Gln Leu Lys Asn Glu Glu Leu Phe Ala Ala Leu Arg Thr Ile Ser
100 105 110
Lys Arg Arg Gly Ile Ser Tyr Leu Asp Asp Ala Glu Asp Asp Ser Thr
115 120 125
Gly Ser Thr Asp Tyr Ala Lys Ser Ile Asp Glu Asn Arg Arg Leu Leu
130 135 140
Lys Asn Lys Thr Pro Gly Gln Ile Gln Leu Glu Arg Leu Glu Lys Tyr
145 150 155 160
Gly Gln Leu Arg Gly Asn Phe Thr Val Tyr Asp Glu Asn Gly Glu Ala
165 170 175
His Arg Leu Ile Asn Val Phe Ser Thr Ser Asp Tyr Glu Lys Glu Ala
180 185 190
Arg Lys Ile Leu Glu Thr Gln Ala Asp Tyr Asn Lys Lys Ile Thr Ala
195 200 205
Glu Phe Ile Asp Asp Tyr Val Glu Ile Leu Thr Gln Lys Arg Lys Tyr
210 215 220
Tyr His Gly Pro Gly Asn Glu Lys Ser Arg Thr Asp Tyr Gly Arg Phe
225 230 235 240
Arg Thr Asp Gly Thr Thr Leu Glu Asn Ile Phe Gly Ile Leu Ile Gly
245 250 255
Lys Cys Asn Phe Tyr Pro Asp Glu Tyr Arg Ala Ser Lys Ala Ser Tyr
260 265 270
Thr Ala Gln Glu Tyr Asn Phe Leu Asn Asp Leu Asn Asn Leu Lys Val
275 280 285
Ser Thr Glu Thr Gly Lys Leu Ser Thr Glu Gln Lys Glu Ser Leu Val
290 295 300
Glu Phe Ala Lys Asn Thr Ala Thr Leu Gly Pro Ala Lys Leu Leu Lys
305 310 315 320
Glu Ile Ala Lys Ile Leu Asp Cys Lys Val Asp Glu Ile Lys Gly Tyr
325 330 335
Arg Glu Asp Asp Lys Gly Lys Pro Asp Leu His Thr Phe Glu Pro Tyr
340 345 350
Arg Lys Leu Lys Phe Asn Leu Glu Ser Ile Asn Ile Asp Asp Leu Ser
355 360 365
Arg Glu Val Ile Asp Lys Leu Ala Asp Ile Leu Thr Leu Asn Thr Glu
370 375 380
Arg Glu Gly Ile Glu Asp Ala Ile Lys Arg Asn Leu Pro Asn Gln Phe
385 390 395 400
Thr Glu Glu Gln Ile Ser Glu Ile Ile Lys Val Arg Lys Ser Gln Ser
405 410 415
Thr Ala Phe Asn Lys Gly Trp His Ser Phe Ser Ala Lys Leu Met Asn
420 425 430
Glu Leu Ile Pro Glu Leu Tyr Ala Thr Ser Asp Glu Gln Met Thr Ile
435 440 445
Leu Thr Arg Leu Glu Lys Phe Lys Val Asn Lys Lys Ser Ser Lys Asn
450 455 460
Thr Lys Thr Ile Asp Glu Lys Glu Val Thr Asp Glu Ile Tyr Asn Pro
465 470 475 480
Val Val Ala Lys Ser Val Arg Gln Thr Ile Lys Ile Ile Asn Ala Ala
485 490 495
Val Lys Lys Tyr Gly Asp Phe Asp Lys Ile Val Ile Glu Met Pro Arg
500 505 510
Asp Lys Asn Ala Asp Asp Glu Lys Lys Phe Ile Asp Lys Arg Asn Lys
515 520 525
Glu Asn Lys Lys Glu Lys Asp Asp Ala Leu Lys Arg Ala Ala Tyr Leu
530 535 540
Tyr Asn Ser Ser Asp Lys Leu Pro Asp Glu Val Phe His Gly Asn Lys
545 550 555 560
Gln Leu Glu Thr Lys Ile Arg Leu Trp Tyr Gln Gln Gly Glu Arg Cys
565 570 575
Leu Tyr Ser Gly Lys Pro Ile Ser Ile Gln Glu Leu Val His Asn Ser
580 585 590
Asn Asn Phe Glu Ile Asp His Ile Leu Pro Leu Ser Leu Ser Phe Asp
595 600 605
Asp Ser Leu Ala Asn Lys Val Leu Val Tyr Ala Trp Thr Asn Gln Glu
610 615 620
Lys Gly Gln Lys Thr Pro Tyr Gln Val Ile Asp Ser Met Asp Ala Ala
625 630 635 640
Trp Ser Phe Arg Glu Met Lys Asp Tyr Val Leu Lys Gln Lys Gly Leu
645 650 655
Gly Lys Lys Lys Arg Asp Tyr Leu Leu Thr Thr Glu Asn Ile Asp Lys
660 665 670
Ile Glu Val Lys Lys Lys Phe Ile Glu Arg Asn Leu Val Asp Thr Arg
675 680 685
Tyr Ala Ser Arg Val Val Leu Asn Ser Leu Gln Ser Ala Leu Arg Glu
690 695 700
Leu Gly Lys Asp Thr Lys Val Ser Val Val Arg Gly Gln Phe Thr Ser
705 710 715 720
Gln Leu Arg Arg Lys Trp Lys Ile Asp Lys Ser Arg Glu Thr Tyr His
725 730 735
His His Ala Val Asp Ala Leu Ile Ile Ala Ala Ser Ser Gln Leu Lys
740 745 750
Leu Trp Glu Lys Gln Asp Asn Pro Met Phe Val Asp Tyr Gly Lys Asn
755 760 765
Gln Val Val Asp Lys Gln Thr Gly Glu Ile Leu Ser Val Ser Asp Asp
770 775 780
Glu Tyr Lys Glu Leu Val Phe Gln Pro Pro Tyr Gln Gly Phe Val Asn
785 790 795 800
Thr Ile Ser Ser Lys Gly Phe Glu Asp Glu Ile Leu Phe Ser Tyr Gln
805 810 815
Val Asp Ser Lys Tyr Asn Arg Lys Val Ser Asp Ala Thr Ile Tyr Ser
820 825 830
Thr Arg Lys Ala Lys Ile Gly Lys Asp Lys Lys Glu Glu Thr Tyr Val
835 840 845
Leu Gly Lys Ile Lys Asp Ile Tyr Ser Gln Asn Gly Phe Asp Thr Phe
850 855 860
Ile Lys Lys Tyr Asn Lys Asp Lys Thr Gln Phe Leu Met Tyr Gln Lys
865 870 875 880
Asp Ser Leu Thr Trp Glu Asn Val Ile Glu Val Ile Leu Arg Asp Tyr
885 890 895
Pro Thr Thr Lys Lys Ser Glu Asp Gly Lys Asn Asp Val Lys Cys Asn
900 905 910
Pro Phe Glu Glu Tyr Arg Arg Glu Asn Gly Leu Ile Cys Lys Tyr Ser
915 920 925
Lys Lys Gly Lys Gly Thr Pro Ile Lys Ser Leu Lys Tyr Tyr Asp Lys
930 935 940
Lys Leu Gly Asn Cys Ile Asp Ile Thr Pro Glu Glu Ser Arg Asn Lys
945 950 955 960
Val Ile Leu Gln Ser Ile Asn Pro Trp Arg Ala Asp Val Tyr Phe Asn
965 970 975
Pro Glu Thr Leu Lys Tyr Glu Leu Met Gly Leu Lys Tyr Ser Asp Leu
980 985 990
Ser Phe Glu Lys Gly Thr Gly Asn Tyr His Ile Ser Gln Glu Lys Tyr
995 1000 1005
Asp Ala Ile Lys Glu Lys Glu Gly Ile Gly Lys Lys Ser Glu Phe
1010 1015 1020
Lys Phe Thr Leu Tyr Arg Asn Asp Leu Ile Leu Ile Lys Asp Ile
1025 1030 1035
Ala Ser Gly Glu Gln Glu Ile Tyr Arg Phe Leu Ser Arg Thr Met
1040 1045 1050
Pro Asn Val Asn His Tyr Val Glu Leu Lys Pro Tyr Asp Lys Glu
1055 1060 1065
Lys Phe Asp Asn Val Gln Glu Leu Val Glu Ala Leu Gly Glu Ala
1070 1075 1080
Asp Lys Val Gly Arg Cys Ile Lys Gly Leu Asn Lys Pro Asn Ile
1085 1090 1095
Ser Ile Tyr Lys Val Arg Thr Asp Val Leu Gly Asn Lys Tyr Phe
1100 1105 1110
Val Lys Lys Lys Gly Asp Lys Pro Lys Leu Asp Phe Lys Asn Asn
1115 1120 1125
Lys Lys
1130
<210> 156
<211> 1082
<212> PRT
<213> 灰色奈瑟球菌（Neisseria cinerea）
<400> 156
Met Ala Ala Phe Lys Pro Asn Pro Met Asn Tyr Ile Leu Gly Leu Asp
1 5 10 15
Ile Gly Ile Ala Ser Val Gly Trp Ala Ile Val Glu Ile Asp Glu Glu
20 25 30
Glu Asn Pro Ile Arg Leu Ile Asp Leu Gly Val Arg Val Phe Glu Arg
35 40 45
Ala Glu Val Pro Lys Thr Gly Asp Ser Leu Ala Ala Ala Arg Arg Leu
50 55 60
Ala Arg Ser Val Arg Arg Leu Thr Arg Arg Arg Ala His Arg Leu Leu
65 70 75 80
Arg Ala Arg Arg Leu Leu Lys Arg Glu Gly Val Leu Gln Ala Ala Asp
85 90 95
Phe Asp Glu Asn Gly Leu Ile Lys Ser Leu Pro Asn Thr Pro Trp Gln
100 105 110
Leu Arg Ala Ala Ala Leu Asp Arg Lys Leu Thr Pro Leu Glu Trp Ser
115 120 125
Ala Val Leu Leu His Leu Ile Lys His Arg Gly Tyr Leu Ser Gln Arg
130 135 140
Lys Asn Glu Gly Glu Thr Ala Asp Lys Glu Leu Gly Ala Leu Leu Lys
145 150 155 160
Gly Val Ala Asp Asn Thr His Ala Leu Gln Thr Gly Asp Phe Arg Thr
165 170 175
Pro Ala Glu Leu Ala Leu Asn Lys Phe Glu Lys Glu Ser Gly His Ile
180 185 190
Arg Asn Gln Arg Gly Asp Tyr Ser His Thr Phe Asn Arg Lys Asp Leu
195 200 205
Gln Ala Glu Leu Asn Leu Leu Phe Glu Lys Gln Lys Glu Phe Gly Asn
210 215 220
Pro His Val Ser Asp Gly Leu Lys Glu Gly Ile Glu Thr Leu Leu Met
225 230 235 240
Thr Gln Arg Pro Ala Leu Ser Gly Asp Ala Val Gln Lys Met Leu Gly
245 250 255
His Cys Thr Phe Glu Pro Thr Glu Pro Lys Ala Ala Lys Asn Thr Tyr
260 265 270
Thr Ala Glu Arg Phe Val Trp Leu Thr Lys Leu Asn Asn Leu Arg Ile
275 280 285
Leu Glu Gln Gly Ser Glu Arg Pro Leu Thr Asp Thr Glu Arg Ala Thr
290 295 300
Leu Met Asp Glu Pro Tyr Arg Lys Ser Lys Leu Thr Tyr Ala Gln Ala
305 310 315 320
Arg Lys Leu Leu Asp Leu Asp Asp Thr Ala Phe Phe Lys Gly Leu Arg
325 330 335
Tyr Gly Lys Asp Asn Ala Glu Ala Ser Thr Leu Met Glu Met Lys Ala
340 345 350
Tyr His Ala Ile Ser Arg Ala Leu Glu Lys Glu Gly Leu Lys Asp Lys
355 360 365
Lys Ser Pro Leu Asn Leu Ser Pro Glu Leu Gln Asp Glu Ile Gly Thr
370 375 380
Ala Phe Ser Leu Phe Lys Thr Asp Glu Asp Ile Thr Gly Arg Leu Lys
385 390 395 400
Asp Arg Val Gln Pro Glu Ile Leu Glu Ala Leu Leu Lys His Ile Ser
405 410 415
Phe Asp Lys Phe Val Gln Ile Ser Leu Lys Ala Leu Arg Arg Ile Val
420 425 430
Pro Leu Met Glu Gln Gly Asn Arg Tyr Asp Glu Ala Cys Thr Glu Ile
435 440 445
Tyr Gly Asp His Tyr Gly Lys Lys Asn Thr Glu Glu Lys Ile Tyr Leu
450 455 460
Pro Pro Ile Pro Ala Asp Glu Ile Arg Asn Pro Val Val Leu Arg Ala
465 470 475 480
Leu Ser Gln Ala Arg Lys Val Ile Asn Gly Val Val Arg Arg Tyr Gly
485 490 495
Ser Pro Ala Arg Ile His Ile Glu Thr Ala Arg Glu Val Gly Lys Ser
500 505 510
Phe Lys Asp Arg Lys Glu Ile Glu Lys Arg Gln Glu Glu Asn Arg Lys
515 520 525
Asp Arg Glu Lys Ser Ala Ala Lys Phe Arg Glu Tyr Phe Pro Asn Phe
530 535 540
Val Gly Glu Pro Lys Ser Lys Asp Ile Leu Lys Leu Arg Leu Tyr Glu
545 550 555 560
Gln Gln His Gly Lys Cys Leu Tyr Ser Gly Lys Glu Ile Asn Leu Gly
565 570 575
Arg Leu Asn Glu Lys Gly Tyr Val Glu Ile Asp His Ala Leu Pro Phe
580 585 590
Ser Arg Thr Trp Asp Asp Ser Phe Asn Asn Lys Val Leu Ala Leu Gly
595 600 605
Ser Glu Asn Gln Asn Lys Gly Asn Gln Thr Pro Tyr Glu Tyr Phe Asn
610 615 620
Gly Lys Asp Asn Ser Arg Glu Trp Gln Glu Phe Lys Ala Arg Val Glu
625 630 635 640
Thr Ser Arg Phe Pro Arg Ser Lys Lys Gln Arg Ile Leu Leu Gln Lys
645 650 655
Phe Asp Glu Asp Gly Phe Lys Glu Arg Asn Leu Asn Asp Thr Arg Tyr
660 665 670
Ile Asn Arg Phe Leu Cys Gln Phe Val Ala Asp His Met Leu Leu Thr
675 680 685
Gly Lys Gly Lys Arg Arg Val Phe Ala Ser Asn Gly Gln Ile Thr Asn
690 695 700
Leu Leu Arg Gly Phe Trp Gly Leu Arg Lys Val Arg Ala Glu Asn Asp
705 710 715 720
Arg His His Ala Leu Asp Ala Val Val Val Ala Cys Ser Thr Ile Ala
725 730 735
Met Gln Gln Lys Ile Thr Arg Phe Val Arg Tyr Lys Glu Met Asn Ala
740 745 750
Phe Asp Gly Lys Thr Ile Asp Lys Glu Thr Gly Glu Val Leu His Gln
755 760 765
Lys Ala His Phe Pro Gln Pro Trp Glu Phe Phe Ala Gln Glu Val Met
770 775 780
Ile Arg Val Phe Gly Lys Pro Asp Gly Lys Pro Glu Phe Glu Glu Ala
785 790 795 800
Asp Thr Pro Glu Lys Leu Arg Thr Leu Leu Ala Glu Lys Leu Ser Ser
805 810 815
Arg Pro Glu Ala Val His Lys Tyr Val Thr Pro Leu Phe Ile Ser Arg
820 825 830
Ala Pro Asn Arg Lys Met Ser Gly Gln Gly His Met Glu Thr Val Lys
835 840 845
Ser Ala Lys Arg Leu Asp Glu Gly Ile Ser Val Leu Arg Val Pro Leu
850 855 860
Thr Gln Leu Lys Leu Lys Asp Leu Glu Lys Met Val Asn Arg Glu Arg
865 870 875 880
Glu Pro Lys Leu Tyr Glu Ala Leu Lys Ala Arg Leu Glu Ala His Lys
885 890 895
Asp Asp Pro Ala Lys Ala Phe Ala Glu Pro Phe Tyr Lys Tyr Asp Lys
900 905 910
Ala Gly Asn Arg Thr Gln Gln Val Lys Ala Val Arg Val Glu Gln Val
915 920 925
Gln Lys Thr Gly Val Trp Val His Asn His Asn Gly Ile Ala Asp Asn
930 935 940
Ala Thr Ile Val Arg Val Asp Val Phe Glu Lys Gly Gly Lys Tyr Tyr
945 950 955 960
Leu Val Pro Ile Tyr Ser Trp Gln Val Ala Lys Gly Ile Leu Pro Asp
965 970 975
Arg Ala Val Val Gln Gly Lys Asp Glu Glu Asp Trp Thr Val Met Asp
980 985 990
Asp Ser Phe Glu Phe Lys Phe Val Leu Tyr Ala Asn Asp Leu Ile Lys
995 1000 1005
Leu Thr Ala Lys Lys Asn Glu Phe Leu Gly Tyr Phe Val Ser Leu
1010 1015 1020
Asn Arg Ala Thr Gly Ala Ile Asp Ile Arg Thr His Asp Thr Asp
1025 1030 1035
Ser Thr Lys Gly Lys Asn Gly Ile Phe Gln Ser Val Gly Val Lys
1040 1045 1050
Thr Ala Leu Ser Phe Gln Lys Tyr Gln Ile Asp Glu Leu Gly Lys
1055 1060 1065
Glu Ile Arg Pro Cys Arg Leu Lys Lys Arg Pro Pro Val Arg
1070 1075 1080
<210> 157
<211> 1003
<212> PRT
<213> 红嘴鸥弯曲杆菌（Campylobacter lari）
<400> 157
Met Arg Ile Leu Gly Phe Asp Ile Gly Ile Asn Ser Ile Gly Trp Ala
1 5 10 15
Phe Val Glu Asn Asp Glu Leu Lys Asp Cys Gly Val Arg Ile Phe Thr
20 25 30
Lys Ala Glu Asn Pro Lys Asn Lys Glu Ser Leu Ala Leu Pro Arg Arg
35 40 45
Asn Ala Arg Ser Ser Arg Arg Arg Leu Lys Arg Arg Lys Ala Arg Leu
50 55 60
Ile Ala Ile Lys Arg Ile Leu Ala Lys Glu Leu Lys Leu Asn Tyr Lys
65 70 75 80
Asp Tyr Val Ala Ala Asp Gly Glu Leu Pro Lys Ala Tyr Glu Gly Ser
85 90 95
Leu Ala Ser Val Tyr Glu Leu Arg Tyr Lys Ala Leu Thr Gln Asn Leu
100 105 110
Glu Thr Lys Asp Leu Ala Arg Val Ile Leu His Ile Ala Lys His Arg
115 120 125
Gly Tyr Met Asn Lys Asn Glu Lys Lys Ser Asn Asp Ala Lys Lys Gly
130 135 140
Lys Ile Leu Ser Ala Leu Lys Asn Asn Ala Leu Lys Leu Glu Asn Tyr
145 150 155 160
Gln Ser Val Gly Glu Tyr Phe Tyr Lys Glu Phe Phe Gln Lys Tyr Lys
165 170 175
Lys Asn Thr Lys Asn Phe Ile Lys Ile Arg Asn Thr Lys Asp Asn Tyr
180 185 190
Asn Asn Cys Val Leu Ser Ser Asp Leu Glu Lys Glu Leu Lys Leu Ile
195 200 205
Leu Glu Lys Gln Lys Glu Phe Gly Tyr Asn Tyr Ser Glu Asp Phe Ile
210 215 220
Asn Glu Ile Leu Lys Val Ala Phe Phe Gln Arg Pro Leu Lys Asp Phe
225 230 235 240
Ser His Leu Val Gly Ala Cys Thr Phe Phe Glu Glu Glu Lys Arg Ala
245 250 255
Cys Lys Asn Ser Tyr Ser Ala Trp Glu Phe Val Ala Leu Thr Lys Ile
260 265 270
Ile Asn Glu Ile Lys Ser Leu Glu Lys Ile Ser Gly Glu Ile Val Pro
275 280 285
Thr Gln Thr Ile Asn Glu Val Leu Asn Leu Ile Leu Asp Lys Gly Ser
290 295 300
Ile Thr Tyr Lys Lys Phe Arg Ser Cys Ile Asn Leu His Glu Ser Ile
305 310 315 320
Ser Phe Lys Ser Leu Lys Tyr Asp Lys Glu Asn Ala Glu Asn Ala Lys
325 330 335
Leu Ile Asp Phe Arg Lys Leu Val Glu Phe Lys Lys Ala Leu Gly Val
340 345 350
His Ser Leu Ser Arg Gln Glu Leu Asp Gln Ile Ser Thr His Ile Thr
355 360 365
Leu Ile Lys Asp Asn Val Lys Leu Lys Thr Val Leu Glu Lys Tyr Asn
370 375 380
Leu Ser Asn Glu Gln Ile Asn Asn Leu Leu Glu Ile Glu Phe Asn Asp
385 390 395 400
Tyr Ile Asn Leu Ser Phe Lys Ala Leu Gly Met Ile Leu Pro Leu Met
405 410 415
Arg Glu Gly Lys Arg Tyr Asp Glu Ala Cys Glu Ile Ala Asn Leu Lys
420 425 430
Pro Lys Thr Val Asp Glu Lys Lys Asp Phe Leu Pro Ala Phe Cys Asp
435 440 445
Ser Ile Phe Ala His Glu Leu Ser Asn Pro Val Val Asn Arg Ala Ile
450 455 460
Ser Glu Tyr Arg Lys Val Leu Asn Ala Leu Leu Lys Lys Tyr Gly Lys
465 470 475 480
Val His Lys Ile His Leu Glu Leu Ala Arg Asp Val Gly Leu Ser Lys
485 490 495
Lys Ala Arg Glu Lys Ile Glu Lys Glu Gln Lys Glu Asn Gln Ala Val
500 505 510
Asn Ala Trp Ala Leu Lys Glu Cys Glu Asn Ile Gly Leu Lys Ala Ser
515 520 525
Ala Lys Asn Ile Leu Lys Leu Lys Leu Trp Lys Glu Gln Lys Glu Ile
530 535 540
Cys Ile Tyr Ser Gly Asn Lys Ile Ser Ile Glu His Leu Lys Asp Glu
545 550 555 560
Lys Ala Leu Glu Val Asp His Ile Tyr Pro Tyr Ser Arg Ser Phe Asp
565 570 575
Asp Ser Phe Ile Asn Lys Val Leu Val Phe Thr Lys Glu Asn Gln Glu
580 585 590
Lys Leu Asn Lys Thr Pro Phe Glu Ala Phe Gly Lys Asn Ile Glu Lys
595 600 605
Trp Ser Lys Ile Gln Thr Leu Ala Gln Asn Leu Pro Tyr Lys Lys Lys
610 615 620
Asn Lys Ile Leu Asp Glu Asn Phe Lys Asp Lys Gln Gln Glu Asp Phe
625 630 635 640
Ile Ser Arg Asn Leu Asn Asp Thr Arg Tyr Ile Ala Thr Leu Ile Ala
645 650 655
Lys Tyr Thr Lys Glu Tyr Leu Asn Phe Leu Leu Leu Ser Glu Asn Glu
660 665 670
Asn Ala Asn Leu Lys Ser Gly Glu Lys Gly Ser Lys Ile His Val Gln
675 680 685
Thr Ile Ser Gly Met Leu Thr Ser Val Leu Arg His Thr Trp Gly Phe
690 695 700
Asp Lys Lys Asp Arg Asn Asn His Leu His His Ala Leu Asp Ala Ile
705 710 715 720
Ile Val Ala Tyr Ser Thr Asn Ser Ile Ile Lys Ala Phe Ser Asp Phe
725 730 735
Arg Lys Asn Gln Glu Leu Leu Lys Ala Arg Phe Tyr Ala Lys Glu Leu
740 745 750
Thr Ser Asp Asn Tyr Lys His Gln Val Lys Phe Phe Glu Pro Phe Lys
755 760 765
Ser Phe Arg Glu Lys Ile Leu Ser Lys Ile Asp Glu Ile Phe Val Ser
770 775 780
Lys Pro Pro Arg Lys Arg Ala Arg Arg Ala Leu His Lys Asp Thr Phe
785 790 795 800
His Ser Glu Asn Lys Ile Ile Asp Lys Cys Ser Tyr Asn Ser Lys Glu
805 810 815
Gly Leu Gln Ile Ala Leu Ser Cys Gly Arg Val Arg Lys Ile Gly Thr
820 825 830
Lys Tyr Val Glu Asn Asp Thr Ile Val Arg Val Asp Ile Phe Lys Lys
835 840 845
Gln Asn Lys Phe Tyr Ala Ile Pro Ile Tyr Ala Met Asp Phe Ala Leu
850 855 860
Gly Ile Leu Pro Asn Lys Ile Val Ile Thr Gly Lys Asp Lys Asn Asn
865 870 875 880
Asn Pro Lys Gln Trp Gln Thr Ile Asp Glu Ser Tyr Glu Phe Cys Phe
885 890 895
Ser Leu Tyr Lys Asn Asp Leu Ile Leu Leu Gln Lys Lys Asn Met Gln
900 905 910
Glu Pro Glu Phe Ala Tyr Tyr Asn Asp Phe Ser Ile Ser Thr Ser Ser
915 920 925
Ile Cys Val Glu Lys His Asp Asn Lys Phe Glu Asn Leu Thr Ser Asn
930 935 940
Gln Lys Leu Leu Phe Ser Asn Ala Lys Glu Gly Ser Val Lys Val Glu
945 950 955 960
Ser Leu Gly Ile Gln Asn Leu Lys Val Phe Glu Lys Tyr Ile Ile Thr
965 970 975
Pro Leu Gly Asp Lys Ile Lys Ala Asp Phe Gln Pro Arg Glu Asn Ile
980 985 990
Ser Leu Lys Thr Ser Lys Lys Tyr Gly Leu Arg
995 1000
<210> 158
<211> 1395
<212> PRT
<213> 齿垢密螺旋体（Treponema denticola）
<400> 158
Met Lys Lys Glu Ile Lys Asp Tyr Phe Leu Gly Leu Asp Val Gly Thr
1 5 10 15
Gly Ser Val Gly Trp Ala Val Thr Asp Thr Asp Tyr Lys Leu Leu Lys
20 25 30
Ala Asn Arg Lys Asp Leu Trp Gly Met Arg Cys Phe Glu Thr Ala Glu
35 40 45
Thr Ala Glu Val Arg Arg Leu His Arg Gly Ala Arg Arg Arg Ile Glu
50 55 60
Arg Arg Lys Lys Arg Ile Lys Leu Leu Gln Glu Leu Phe Ser Gln Glu
65 70 75 80
Ile Ala Lys Thr Asp Glu Gly Phe Phe Gln Arg Met Lys Glu Ser Pro
85 90 95
Phe Tyr Ala Glu Asp Lys Thr Ile Leu Gln Glu Asn Thr Leu Phe Asn
100 105 110
Asp Lys Asp Phe Ala Asp Lys Thr Tyr His Lys Ala Tyr Pro Thr Ile
115 120 125
Asn His Leu Ile Lys Ala Trp Ile Glu Asn Lys Val Lys Pro Asp Pro
130 135 140
Arg Leu Leu Tyr Leu Ala Cys His Asn Ile Ile Lys Lys Arg Gly His
145 150 155 160
Phe Leu Phe Glu Gly Asp Phe Asp Ser Glu Asn Gln Phe Asp Thr Ser
165 170 175
Ile Gln Ala Leu Phe Glu Tyr Leu Arg Glu Asp Met Glu Val Asp Ile
180 185 190
Asp Ala Asp Ser Gln Lys Val Lys Glu Ile Leu Lys Asp Ser Ser Leu
195 200 205
Lys Asn Ser Glu Lys Gln Ser Arg Leu Asn Lys Ile Leu Gly Leu Lys
210 215 220
Pro Ser Asp Lys Gln Lys Lys Ala Ile Thr Asn Leu Ile Ser Gly Asn
225 230 235 240
Lys Ile Asn Phe Ala Asp Leu Tyr Asp Asn Pro Asp Leu Lys Asp Ala
245 250 255
Glu Lys Asn Ser Ile Ser Phe Ser Lys Asp Asp Phe Asp Ala Leu Ser
260 265 270
Asp Asp Leu Ala Ser Ile Leu Gly Asp Ser Phe Glu Leu Leu Leu Lys
275 280 285
Ala Lys Ala Val Tyr Asn Cys Ser Val Leu Ser Lys Val Ile Gly Asp
290 295 300
Glu Gln Tyr Leu Ser Phe Ala Lys Val Lys Ile Tyr Glu Lys His Lys
305 310 315 320
Thr Asp Leu Thr Lys Leu Lys Asn Val Ile Lys Lys His Phe Pro Lys
325 330 335
Asp Tyr Lys Lys Val Phe Gly Tyr Asn Lys Asn Glu Lys Asn Asn Asn
340 345 350
Asn Tyr Ser Gly Tyr Val Gly Val Cys Lys Thr Lys Ser Lys Lys Leu
355 360 365
Ile Ile Asn Asn Ser Val Asn Gln Glu Asp Phe Tyr Lys Phe Leu Lys
370 375 380
Thr Ile Leu Ser Ala Lys Ser Glu Ile Lys Glu Val Asn Asp Ile Leu
385 390 395 400
Thr Glu Ile Glu Thr Gly Thr Phe Leu Pro Lys Gln Ile Ser Lys Ser
405 410 415
Asn Ala Glu Ile Pro Tyr Gln Leu Arg Lys Met Glu Leu Glu Lys Ile
420 425 430
Leu Ser Asn Ala Glu Lys His Phe Ser Phe Leu Lys Gln Lys Asp Glu
435 440 445
Lys Gly Leu Ser His Ser Glu Lys Ile Ile Met Leu Leu Thr Phe Lys
450 455 460
Ile Pro Tyr Tyr Ile Gly Pro Ile Asn Asp Asn His Lys Lys Phe Phe
465 470 475 480
Pro Asp Arg Cys Trp Val Val Lys Lys Glu Lys Ser Pro Ser Gly Lys
485 490 495
Thr Thr Pro Trp Asn Phe Phe Asp His Ile Asp Lys Glu Lys Thr Ala
500 505 510
Glu Ala Phe Ile Thr Ser Arg Thr Asn Phe Cys Thr Tyr Leu Val Gly
515 520 525
Glu Ser Val Leu Pro Lys Ser Ser Leu Leu Tyr Ser Glu Tyr Thr Val
530 535 540
Leu Asn Glu Ile Asn Asn Leu Gln Ile Ile Ile Asp Gly Lys Asn Ile
545 550 555 560
Cys Asp Ile Lys Leu Lys Gln Lys Ile Tyr Glu Asp Leu Phe Lys Lys
565 570 575
Tyr Lys Lys Ile Thr Gln Lys Gln Ile Ser Thr Phe Ile Lys His Glu
580 585 590
Gly Ile Cys Asn Lys Thr Asp Glu Val Ile Ile Leu Gly Ile Asp Lys
595 600 605
Glu Cys Thr Ser Ser Leu Lys Ser Tyr Ile Glu Leu Lys Asn Ile Phe
610 615 620
Gly Lys Gln Val Asp Glu Ile Ser Thr Lys Asn Met Leu Glu Glu Ile
625 630 635 640
Ile Arg Trp Ala Thr Ile Tyr Asp Glu Gly Glu Gly Lys Thr Ile Leu
645 650 655
Lys Thr Lys Ile Lys Ala Glu Tyr Gly Lys Tyr Cys Ser Asp Glu Gln
660 665 670
Ile Lys Lys Ile Leu Asn Leu Lys Phe Ser Gly Trp Gly Arg Leu Ser
675 680 685
Arg Lys Phe Leu Glu Thr Val Thr Ser Glu Met Pro Gly Phe Ser Glu
690 695 700
Pro Val Asn Ile Ile Thr Ala Met Arg Glu Thr Gln Asn Asn Leu Met
705 710 715 720
Glu Leu Leu Ser Ser Glu Phe Thr Phe Thr Glu Asn Ile Lys Lys Ile
725 730 735
Asn Ser Gly Phe Glu Asp Ala Glu Lys Gln Phe Ser Tyr Asp Gly Leu
740 745 750
Val Lys Pro Leu Phe Leu Ser Pro Ser Val Lys Lys Met Leu Trp Gln
755 760 765
Thr Leu Lys Leu Val Lys Glu Ile Ser His Ile Thr Gln Ala Pro Pro
770 775 780
Lys Lys Ile Phe Ile Glu Met Ala Lys Gly Ala Glu Leu Glu Pro Ala
785 790 795 800
Arg Thr Lys Thr Arg Leu Lys Ile Leu Gln Asp Leu Tyr Asn Asn Cys
805 810 815
Lys Asn Asp Ala Asp Ala Phe Ser Ser Glu Ile Lys Asp Leu Ser Gly
820 825 830
Lys Ile Glu Asn Glu Asp Asn Leu Arg Leu Arg Ser Asp Lys Leu Tyr
835 840 845
Leu Tyr Tyr Thr Gln Leu Gly Lys Cys Met Tyr Cys Gly Lys Pro Ile
850 855 860
Glu Ile Gly His Val Phe Asp Thr Ser Asn Tyr Asp Ile Asp His Ile
865 870 875 880
Tyr Pro Gln Ser Lys Ile Lys Asp Asp Ser Ile Ser Asn Arg Val Leu
885 890 895
Val Cys Ser Ser Cys Asn Lys Asn Lys Glu Asp Lys Tyr Pro Leu Lys
900 905 910
Ser Glu Ile Gln Ser Lys Gln Arg Gly Phe Trp Asn Phe Leu Gln Arg
915 920 925
Asn Asn Phe Ile Ser Leu Glu Lys Leu Asn Arg Leu Thr Arg Ala Thr
930 935 940
Pro Ile Ser Asp Asp Glu Thr Ala Lys Phe Ile Ala Arg Gln Leu Val
945 950 955 960
Glu Thr Arg Gln Ala Thr Lys Val Ala Ala Lys Val Leu Glu Lys Met
965 970 975
Phe Pro Glu Thr Lys Ile Val Tyr Ser Lys Ala Glu Thr Val Ser Met
980 985 990
Phe Arg Asn Lys Phe Asp Ile Val Lys Cys Arg Glu Ile Asn Asp Phe
995 1000 1005
His His Ala His Asp Ala Tyr Leu Asn Ile Val Val Gly Asn Val
1010 1015 1020
Tyr Asn Thr Lys Phe Thr Asn Asn Pro Trp Asn Phe Ile Lys Glu
1025 1030 1035
Lys Arg Asp Asn Pro Lys Ile Ala Asp Thr Tyr Asn Tyr Tyr Lys
1040 1045 1050
Val Phe Asp Tyr Asp Val Lys Arg Asn Asn Ile Thr Ala Trp Glu
1055 1060 1065
Lys Gly Lys Thr Ile Ile Thr Val Lys Asp Met Leu Lys Arg Asn
1070 1075 1080
Thr Pro Ile Tyr Thr Arg Gln Ala Ala Cys Lys Lys Gly Glu Leu
1085 1090 1095
Phe Asn Gln Thr Ile Met Lys Lys Gly Leu Gly Gln His Pro Leu
1100 1105 1110
Lys Lys Glu Gly Pro Phe Ser Asn Ile Ser Lys Tyr Gly Gly Tyr
1115 1120 1125
Asn Lys Val Ser Ala Ala Tyr Tyr Thr Leu Ile Glu Tyr Glu Glu
1130 1135 1140
Lys Gly Asn Lys Ile Arg Ser Leu Glu Thr Ile Pro Leu Tyr Leu
1145 1150 1155
Val Lys Asp Ile Gln Lys Asp Gln Asp Val Leu Lys Ser Tyr Leu
1160 1165 1170
Thr Asp Leu Leu Gly Lys Lys Glu Phe Lys Ile Leu Val Pro Lys
1175 1180 1185
Ile Lys Ile Asn Ser Leu Leu Lys Ile Asn Gly Phe Pro Cys His
1190 1195 1200
Ile Thr Gly Lys Thr Asn Asp Ser Phe Leu Leu Arg Pro Ala Val
1205 1210 1215
Gln Phe Cys Cys Ser Asn Asn Glu Val Leu Tyr Phe Lys Lys Ile
1220 1225 1230
Ile Arg Phe Ser Glu Ile Arg Ser Gln Arg Glu Lys Ile Gly Lys
1235 1240 1245
Thr Ile Ser Pro Tyr Glu Asp Leu Ser Phe Arg Ser Tyr Ile Lys
1250 1255 1260
Glu Asn Leu Trp Lys Lys Thr Lys Asn Asp Glu Ile Gly Glu Lys
1265 1270 1275
Glu Phe Tyr Asp Leu Leu Gln Lys Lys Asn Leu Glu Ile Tyr Asp
1280 1285 1290
Met Leu Leu Thr Lys His Lys Asp Thr Ile Tyr Lys Lys Arg Pro
1295 1300 1305
Asn Ser Ala Thr Ile Asp Ile Leu Val Lys Gly Lys Glu Lys Phe
1310 1315 1320
Lys Ser Leu Ile Ile Glu Asn Gln Phe Glu Val Ile Leu Glu Ile
1325 1330 1335
Leu Lys Leu Phe Ser Ala Thr Arg Asn Val Ser Asp Leu Gln His
1340 1345 1350
Ile Gly Gly Ser Lys Tyr Ser Gly Val Ala Lys Ile Gly Asn Lys
1355 1360 1365
Ile Ser Ser Leu Asp Asn Cys Ile Leu Ile Tyr Gln Ser Ile Thr
1370 1375 1380
Gly Ile Phe Glu Lys Arg Ile Asp Leu Leu Lys Val
1385 1390 1395
<210> 159
<211> 1345
<212> PRT
<213> 变形链球菌（Streptococcus mutans）
<400> 159
Met Lys Lys Pro Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val
1 5 10 15
Gly Trp Ala Val Val Thr Asp Asp Tyr Lys Val Pro Ala Lys Lys Met
20 25 30
Lys Val Leu Gly Asn Thr Asp Lys Ser His Ile Glu Lys Asn Leu Leu
35 40 45
Gly Ala Leu Leu Phe Asp Ser Gly Asn Thr Ala Glu Asp Arg Arg Leu
50 55 60
Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Arg Asn Arg Ile Leu
65 70 75 80
Tyr Leu Gln Glu Ile Phe Ser Glu Glu Met Gly Lys Val Asp Asp Ser
85 90 95
Phe Phe His Arg Leu Glu Asp Ser Phe Leu Val Thr Glu Asp Lys Arg
100 105 110
Gly Glu Arg His Pro Ile Phe Gly Asn Leu Glu Glu Glu Val Lys Tyr
115 120 125
His Glu Asn Phe Pro Thr Ile Tyr His Leu Arg Gln Tyr Leu Ala Asp
130 135 140
Asn Pro Glu Lys Val Asp Leu Arg Leu Val Tyr Leu Ala Leu Ala His
145 150 155 160
Ile Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Lys Phe Asp Thr
165 170 175
Arg Asn Asn Asp Val Gln Arg Leu Phe Gln Glu Phe Leu Ala Val Tyr
180 185 190
Asp Asn Thr Phe Glu Asn Ser Ser Leu Gln Glu Gln Asn Val Gln Val
195 200 205
Glu Glu Ile Leu Thr Asp Lys Ile Ser Lys Ser Ala Lys Lys Asp Arg
210 215 220
Val Leu Lys Leu Phe Pro Asn Glu Lys Ser Asn Gly Arg Phe Ala Glu
225 230 235 240
Phe Leu Lys Leu Ile Val Gly Asn Gln Ala Asp Phe Lys Lys His Phe
245 250 255
Glu Leu Glu Glu Lys Ala Pro Leu Gln Phe Ser Lys Asp Thr Tyr Glu
260 265 270
Glu Glu Leu Glu Val Leu Leu Ala Gln Ile Gly Asp Asn Tyr Ala Glu
275 280 285
Leu Phe Leu Ser Ala Lys Lys Leu Tyr Asp Ser Ile Leu Leu Ser Gly
290 295 300
Ile Leu Thr Val Thr Asp Val Gly Thr Lys Ala Pro Leu Ser Ala Ser
305 310 315 320
Met Ile Gln Arg Tyr Asn Glu His Gln Met Asp Leu Ala Gln Leu Lys
325 330 335
Gln Phe Ile Arg Gln Lys Leu Ser Asp Lys Tyr Asn Glu Val Phe Ser
340 345 350
Asp Val Ser Lys Asp Gly Tyr Ala Gly Tyr Ile Asp Gly Lys Thr Asn
355 360 365
Gln Glu Ala Phe Tyr Lys Tyr Leu Lys Gly Leu Leu Asn Lys Ile Glu
370 375 380
Gly Ser Gly Tyr Phe Leu Asp Lys Ile Glu Arg Glu Asp Phe Leu Arg
385 390 395 400
Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu
405 410 415
Gln Glu Met Arg Ala Ile Ile Arg Arg Gln Ala Glu Phe Tyr Pro Phe
420 425 430
Leu Ala Asp Asn Gln Asp Arg Ile Glu Lys Leu Leu Thr Phe Arg Ile
435 440 445
Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Lys Ser Asp Phe Ala Trp
450 455 460
Leu Ser Arg Lys Ser Ala Asp Lys Ile Thr Pro Trp Asn Phe Asp Glu
465 470 475 480
Ile Val Asp Lys Glu Ser Ser Ala Glu Ala Phe Ile Asn Arg Met Thr
485 490 495
Asn Tyr Asp Leu Tyr Leu Pro Asn Gln Lys Val Leu Pro Lys His Ser
500 505 510
Leu Leu Tyr Glu Lys Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys
515 520 525
Tyr Lys Thr Glu Gln Gly Lys Thr Ala Phe Phe Asp Ala Asn Met Lys
530 535 540
Gln Glu Ile Phe Asp Gly Val Phe Lys Val Tyr Arg Lys Val Thr Lys
545 550 555 560
Asp Lys Leu Met Asp Phe Leu Glu Lys Glu Phe Asp Glu Phe Arg Ile
565 570 575
Val Asp Leu Thr Gly Leu Asp Lys Glu Asn Lys Val Phe Asn Ala Ser
580 585 590
Tyr Gly Thr Tyr His Asp Leu Cys Lys Ile Leu Asp Lys Asp Phe Leu
595 600 605
Asp Asn Ser Lys Asn Glu Lys Ile Leu Glu Asp Ile Val Leu Thr Leu
610 615 620
Thr Leu Phe Glu Asp Arg Glu Met Ile Arg Lys Arg Leu Glu Asn Tyr
625 630 635 640
Ser Asp Leu Leu Thr Lys Glu Gln Val Lys Lys Leu Glu Arg Arg His
645 650 655
Tyr Thr Gly Trp Gly Arg Leu Ser Ala Glu Leu Ile His Gly Ile Arg
660 665 670
Asn Lys Glu Ser Arg Lys Thr Ile Leu Asp Tyr Leu Ile Asp Asp Gly
675 680 685
Asn Ser Asn Arg Asn Phe Met Gln Leu Ile Asn Asp Asp Ala Leu Ser
690 695 700
Phe Lys Glu Glu Ile Ala Lys Ala Gln Val Ile Gly Glu Thr Asp Asn
705 710 715 720
Leu Asn Gln Val Val Ser Asp Ile Ala Gly Ser Pro Ala Ile Lys Lys
725 730 735
Gly Ile Leu Gln Ser Leu Lys Ile Val Asp Glu Leu Val Lys Ile Met
740 745 750
Gly His Gln Pro Glu Asn Ile Val Val Glu Met Ala Arg Glu Asn Gln
755 760 765
Phe Thr Asn Gln Gly Arg Arg Asn Ser Gln Gln Arg Leu Lys Gly Leu
770 775 780
Thr Asp Ser Ile Lys Glu Phe Gly Ser Gln Ile Leu Lys Glu His Pro
785 790 795 800
Val Glu Asn Ser Gln Leu Gln Asn Asp Arg Leu Phe Leu Tyr Tyr Leu
805 810 815
Gln Asn Gly Arg Asp Met Tyr Thr Gly Glu Glu Leu Asp Ile Asp Tyr
820 825 830
Leu Ser Gln Tyr Asp Ile Asp His Ile Ile Pro Gln Ala Phe Ile Lys
835 840 845
Asp Asn Ser Ile Asp Asn Arg Val Leu Thr Ser Ser Lys Glu Asn Arg
850 855 860
Gly Lys Ser Asp Asp Val Pro Ser Lys Asp Val Val Arg Lys Met Lys
865 870 875 880
Ser Tyr Trp Ser Lys Leu Leu Ser Ala Lys Leu Ile Thr Gln Arg Lys
885 890 895
Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Thr Asp Asp Asp
900 905 910
Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr
915 920 925
Lys His Val Ala Arg Ile Leu Asp Glu Arg Phe Asn Thr Glu Thr Asp
930 935 940
Glu Asn Asn Lys Lys Ile Arg Gln Val Lys Ile Val Thr Leu Lys Ser
945 950 955 960
Asn Leu Val Ser Asn Phe Arg Lys Glu Phe Glu Leu Tyr Lys Val Arg
965 970 975
Glu Ile Asn Asp Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val
980 985 990
Ile Gly Lys Ala Leu Leu Gly Val Tyr Pro Gln Leu Glu Pro Glu Phe
995 1000 1005
Val Tyr Gly Asp Tyr Pro His Phe His Gly His Lys Glu Asn Lys
1010 1015 1020
Ala Thr Ala Lys Lys Phe Phe Tyr Ser Asn Ile Met Asn Phe Phe
1025 1030 1035
Lys Lys Asp Asp Val Arg Thr Asp Lys Asn Gly Glu Ile Ile Trp
1040 1045 1050
Lys Lys Asp Glu His Ile Ser Asn Ile Lys Lys Val Leu Ser Tyr
1055 1060 1065
Pro Gln Val Asn Ile Val Lys Lys Val Glu Glu Gln Thr Gly Gly
1070 1075 1080
Phe Ser Lys Glu Ser Ile Leu Pro Lys Gly Asn Ser Asp Lys Leu
1085 1090 1095
Ile Pro Arg Lys Thr Lys Lys Phe Tyr Trp Asp Thr Lys Lys Tyr
1100 1105 1110
Gly Gly Phe Asp Ser Pro Ile Val Ala Tyr Ser Ile Leu Val Ile
1115 1120 1125
Ala Asp Ile Glu Lys Gly Lys Ser Lys Lys Leu Lys Thr Val Lys
1130 1135 1140
Ala Leu Val Gly Val Thr Ile Met Glu Lys Met Thr Phe Glu Arg
1145 1150 1155
Asp Pro Val Ala Phe Leu Glu Arg Lys Gly Tyr Arg Asn Val Gln
1160 1165 1170
Glu Glu Asn Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Lys Leu
1175 1180 1185
Glu Asn Gly Arg Lys Arg Leu Leu Ala Ser Ala Arg Glu Leu Gln
1190 1195 1200
Lys Gly Asn Glu Ile Val Leu Pro Asn His Leu Gly Thr Leu Leu
1205 1210 1215
Tyr His Ala Lys Asn Ile His Lys Val Asp Glu Pro Lys His Leu
1220 1225 1230
Asp Tyr Val Asp Lys His Lys Asp Glu Phe Lys Glu Leu Leu Asp
1235 1240 1245
Val Val Ser Asn Phe Ser Lys Lys Tyr Thr Leu Ala Glu Gly Asn
1250 1255 1260
Leu Glu Lys Ile Lys Glu Leu Tyr Ala Gln Asn Asn Gly Glu Asp
1265 1270 1275
Leu Lys Glu Leu Ala Ser Ser Phe Ile Asn Leu Leu Thr Phe Thr
1280 1285 1290
Ala Ile Gly Ala Pro Ala Thr Phe Lys Phe Phe Asp Lys Asn Ile
1295 1300 1305
Asp Arg Lys Arg Tyr Thr Ser Thr Thr Glu Ile Leu Asn Ala Thr
1310 1315 1320
Leu Ile His Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp
1325 1330 1335
Leu Asn Lys Leu Gly Gly Asp
1340 1345
<210> 160
<211> 1388
<212> PRT
<213> 嗜热链球菌（Streptococcus thermophilus）
<400> 160
Met Thr Lys Pro Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val
1 5 10 15
Gly Trp Ala Val Thr Thr Asp Asn Tyr Lys Val Pro Ser Lys Lys Met
20 25 30
Lys Val Leu Gly Asn Thr Ser Lys Lys Tyr Ile Lys Lys Asn Leu Leu
35 40 45
Gly Val Leu Leu Phe Asp Ser Gly Ile Thr Ala Glu Gly Arg Arg Leu
50 55 60
Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Arg Asn Arg Ile Leu
65 70 75 80
Tyr Leu Gln Glu Ile Phe Ser Thr Glu Met Ala Thr Leu Asp Asp Ala
85 90 95
Phe Phe Gln Arg Leu Asp Asp Ser Phe Leu Val Pro Asp Asp Lys Arg
100 105 110
Asp Ser Lys Tyr Pro Ile Phe Gly Asn Leu Val Glu Glu Lys Ala Tyr
115 120 125
His Asp Glu Phe Pro Thr Ile Tyr His Leu Arg Lys Tyr Leu Ala Asp
130 135 140
Ser Thr Lys Lys Ala Asp Leu Arg Leu Val Tyr Leu Ala Leu Ala His
145 150 155 160
Met Ile Lys Tyr Arg Gly His Phe Leu Ile Glu Gly Glu Phe Asn Ser
165 170 175
Lys Asn Asn Asp Ile Gln Lys Asn Phe Gln Asp Phe Leu Asp Thr Tyr
180 185 190
Asn Ala Ile Phe Glu Ser Asp Leu Ser Leu Glu Asn Ser Lys Gln Leu
195 200 205
Glu Glu Ile Val Lys Asp Lys Ile Ser Lys Leu Glu Lys Lys Asp Arg
210 215 220
Ile Leu Lys Leu Phe Pro Gly Glu Lys Asn Ser Gly Ile Phe Ser Glu
225 230 235 240
Phe Leu Lys Leu Ile Val Gly Asn Gln Ala Asp Phe Arg Lys Cys Phe
245 250 255
Asn Leu Asp Glu Lys Ala Ser Leu His Phe Ser Lys Glu Ser Tyr Asp
260 265 270
Glu Asp Leu Glu Thr Leu Leu Gly Tyr Ile Gly Asp Asp Tyr Ser Asp
275 280 285
Val Phe Leu Lys Ala Lys Lys Leu Tyr Asp Ala Ile Leu Leu Ser Gly
290 295 300
Phe Leu Thr Val Thr Asp Asn Glu Thr Glu Ala Pro Leu Ser Ser Ala
305 310 315 320
Met Ile Lys Arg Tyr Asn Glu His Lys Glu Asp Leu Ala Leu Leu Lys
325 330 335
Glu Tyr Ile Arg Asn Ile Ser Leu Lys Thr Tyr Asn Glu Val Phe Lys
340 345 350
Asp Asp Thr Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Lys Thr Asn
355 360 365
Gln Glu Asp Phe Tyr Val Tyr Leu Lys Lys Leu Leu Ala Glu Phe Glu
370 375 380
Gly Ala Asp Tyr Phe Leu Glu Lys Ile Asp Arg Glu Asp Phe Leu Arg
385 390 395 400
Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro Tyr Gln Ile His Leu
405 410 415
Gln Glu Met Arg Ala Ile Leu Asp Lys Gln Ala Lys Phe Tyr Pro Phe
420 425 430
Leu Ala Lys Asn Lys Glu Arg Ile Glu Lys Ile Leu Thr Phe Arg Ile
435 440 445
Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Asp Phe Ala Trp
450 455 460
Ser Ile Arg Lys Arg Asn Glu Lys Ile Thr Pro Trp Asn Phe Glu Asp
465 470 475 480
Val Ile Asp Lys Glu Ser Ser Ala Glu Ala Phe Ile Asn Arg Met Thr
485 490 495
Ser Phe Asp Leu Tyr Leu Pro Glu Glu Lys Val Leu Pro Lys His Ser
500 505 510
Leu Leu Tyr Glu Thr Phe Asn Val Tyr Asn Glu Leu Thr Lys Val Arg
515 520 525
Phe Ile Ala Glu Ser Met Arg Asp Tyr Gln Phe Leu Asp Ser Lys Gln
530 535 540
Lys Lys Asp Ile Val Arg Leu Tyr Phe Lys Asp Lys Arg Lys Val Thr
545 550 555 560
Asp Lys Asp Ile Ile Glu Tyr Leu His Ala Ile Tyr Gly Tyr Asp Gly
565 570 575
Ile Glu Leu Lys Gly Ile Glu Lys Gln Phe Asn Ser Ser Leu Ser Thr
580 585 590
Tyr His Asp Leu Leu Asn Ile Ile Asn Asp Lys Glu Phe Leu Asp Asp
595 600 605
Ser Ser Asn Glu Ala Ile Ile Glu Glu Ile Ile His Thr Leu Thr Ile
610 615 620
Phe Glu Asp Arg Glu Met Ile Lys Gln Arg Leu Ser Lys Phe Glu Asn
625 630 635 640
Ile Phe Asp Lys Ser Val Leu Lys Lys Leu Ser Arg Arg His Tyr Thr
645 650 655
Gly Trp Gly Lys Leu Ser Ala Lys Leu Ile Asn Gly Ile Arg Asp Glu
660 665 670
Lys Ser Gly Asn Thr Ile Leu Asp Tyr Leu Ile Asp Asp Gly Ile Ser
675 680 685
Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ala Leu Ser Phe Lys
690 695 700
Lys Lys Ile Gln Lys Ala Gln Ile Ile Gly Asp Glu Asp Lys Gly Asn
705 710 715 720
Ile Lys Glu Val Val Lys Ser Leu Pro Gly Ser Pro Ala Ile Lys Lys
725 730 735
Gly Ile Leu Gln Ser Ile Lys Ile Val Asp Glu Leu Val Lys Val Met
740 745 750
Gly Gly Arg Lys Pro Glu Ser Ile Val Val Glu Met Ala Arg Glu Asn
755 760 765
Gln Tyr Thr Asn Gln Gly Lys Ser Asn Ser Gln Gln Arg Leu Lys Arg
770 775 780
Leu Glu Lys Ser Leu Lys Glu Leu Gly Ser Lys Ile Leu Lys Glu Asn
785 790 795 800
Ile Pro Ala Lys Leu Ser Lys Ile Asp Asn Asn Ala Leu Gln Asn Asp
805 810 815
Arg Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Lys Asp Met Tyr Thr Gly
820 825 830
Asp Asp Leu Asp Ile Asp Arg Leu Ser Asn Tyr Asp Ile Asp His Ile
835 840 845
Ile Pro Gln Ala Phe Leu Lys Asp Asn Ser Ile Asp Asn Lys Val Leu
850 855 860
Val Ser Ser Ala Ser Asn Arg Gly Lys Ser Asp Asp Val Pro Ser Leu
865 870 875 880
Glu Val Val Lys Lys Arg Lys Thr Phe Trp Tyr Gln Leu Leu Lys Ser
885 890 895
Lys Leu Ile Ser Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg
900 905 910
Gly Gly Leu Ser Pro Glu Asp Lys Ala Gly Phe Ile Gln Arg Gln Leu
915 920 925
Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Arg Leu Leu Asp Glu
930 935 940
Lys Phe Asn Asn Lys Lys Asp Glu Asn Asn Arg Ala Val Arg Thr Val
945 950 955 960
Lys Ile Ile Thr Leu Lys Ser Thr Leu Val Ser Gln Phe Arg Lys Asp
965 970 975
Phe Glu Leu Tyr Lys Val Arg Glu Ile Asn Asp Phe His His Ala His
980 985 990
Asp Ala Tyr Leu Asn Ala Val Val Ala Ser Ala Leu Leu Lys Lys Tyr
995 1000 1005
Pro Lys Leu Glu Pro Glu Phe Val Tyr Gly Asp Tyr Pro Lys Tyr
1010 1015 1020
Asn Ser Phe Arg Glu Arg Lys Ser Ala Thr Glu Lys Val Tyr Phe
1025 1030 1035
Tyr Ser Asn Ile Met Asn Ile Phe Lys Lys Ser Ile Ser Leu Ala
1040 1045 1050
Asp Gly Arg Val Ile Glu Arg Pro Leu Ile Glu Val Asn Glu Glu
1055 1060 1065
Thr Gly Glu Ser Val Trp Asn Lys Glu Ser Asp Leu Ala Thr Val
1070 1075 1080
Arg Arg Val Leu Ser Tyr Pro Gln Val Asn Val Val Lys Lys Val
1085 1090 1095
Glu Glu Gln Asn His Gly Leu Asp Arg Gly Lys Pro Lys Gly Leu
1100 1105 1110
Phe Asn Ala Asn Leu Ser Ser Lys Pro Lys Pro Asn Ser Asn Glu
1115 1120 1125
Asn Leu Val Gly Ala Lys Glu Tyr Leu Asp Pro Lys Lys Tyr Gly
1130 1135 1140
Gly Tyr Ala Gly Ile Ser Asn Ser Phe Thr Val Leu Val Lys Gly
1145 1150 1155
Thr Ile Glu Lys Gly Ala Lys Lys Lys Ile Thr Asn Val Leu Glu
1160 1165 1170
Phe Gln Gly Ile Ser Ile Leu Asp Arg Ile Asn Tyr Arg Lys Asp
1175 1180 1185
Lys Leu Asn Phe Leu Leu Glu Lys Gly Tyr Lys Asp Ile Glu Leu
1190 1195 1200
Ile Ile Glu Leu Pro Lys Tyr Ser Leu Phe Glu Leu Ser Asp Gly
1205 1210 1215
Ser Arg Arg Met Leu Ala Ser Ile Leu Ser Thr Asn Asn Lys Arg
1220 1225 1230
Gly Glu Ile His Lys Gly Asn Gln Ile Phe Leu Ser Gln Lys Phe
1235 1240 1245
Val Lys Leu Leu Tyr His Ala Lys Arg Ile Ser Asn Thr Ile Asn
1250 1255 1260
Glu Asn His Arg Lys Tyr Val Glu Asn His Lys Lys Glu Phe Glu
1265 1270 1275
Glu Leu Phe Tyr Tyr Ile Leu Glu Phe Asn Glu Asn Tyr Val Gly
1280 1285 1290
Ala Lys Lys Asn Gly Lys Leu Leu Asn Ser Ala Phe Gln Ser Trp
1295 1300 1305
Gln Asn His Ser Ile Asp Glu Leu Cys Ser Ser Phe Ile Gly Pro
1310 1315 1320
Thr Gly Ser Glu Arg Lys Gly Leu Phe Glu Leu Thr Ser Arg Gly
1325 1330 1335
Ser Ala Ala Asp Phe Glu Phe Leu Gly Val Lys Ile Pro Arg Tyr
1340 1345 1350
Arg Asp Tyr Thr Pro Ser Ser Leu Leu Lys Asp Ala Thr Leu Ile
1355 1360 1365
His Gln Ser Val Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ala
1370 1375 1380
Lys Leu Gly Glu Gly
1385
<210> 161
<211> 984
<212> PRT
<213> 空肠弯曲杆菌（Campylobacter jejuni）
<400> 161
Met Ala Arg Ile Leu Ala Phe Asp Ile Gly Ile Ser Ser Ile Gly Trp
1 5 10 15
Ala Phe Ser Glu Asn Asp Glu Leu Lys Asp Cys Gly Val Arg Ile Phe
20 25 30
Thr Lys Val Glu Asn Pro Lys Thr Gly Glu Ser Leu Ala Leu Pro Arg
35 40 45
Arg Leu Ala Arg Ser Ala Arg Lys Arg Leu Ala Arg Arg Lys Ala Arg
50 55 60
Leu Asn His Leu Lys His Leu Ile Ala Asn Glu Phe Lys Leu Asn Tyr
65 70 75 80
Glu Asp Tyr Gln Ser Phe Asp Glu Ser Leu Ala Lys Ala Tyr Lys Gly
85 90 95
Ser Leu Ile Ser Pro Tyr Glu Leu Arg Phe Arg Ala Leu Asn Glu Leu
100 105 110
Leu Ser Lys Gln Asp Phe Ala Arg Val Ile Leu His Ile Ala Lys Arg
115 120 125
Arg Gly Tyr Asp Asp Ile Lys Asn Ser Asp Asp Lys Glu Lys Gly Ala
130 135 140
Ile Leu Lys Ala Ile Lys Gln Asn Glu Glu Lys Leu Ala Asn Tyr Gln
145 150 155 160
Ser Val Gly Glu Tyr Leu Tyr Lys Glu Tyr Phe Gln Lys Phe Lys Glu
165 170 175
Asn Ser Lys Glu Phe Thr Asn Val Arg Asn Lys Lys Glu Ser Tyr Glu
180 185 190
Arg Cys Ile Ala Gln Ser Phe Leu Lys Asp Glu Leu Lys Leu Ile Phe
195 200 205
Lys Lys Gln Arg Glu Phe Gly Phe Ser Phe Ser Lys Lys Phe Glu Glu
210 215 220
Glu Val Leu Ser Val Ala Phe Tyr Lys Arg Ala Leu Lys Asp Phe Ser
225 230 235 240
His Leu Val Gly Asn Cys Ser Phe Phe Thr Asp Glu Lys Arg Ala Pro
245 250 255
Lys Asn Ser Pro Leu Ala Phe Met Phe Val Ala Leu Thr Arg Ile Ile
260 265 270
Asn Leu Leu Asn Asn Leu Lys Asn Thr Glu Gly Ile Leu Tyr Thr Lys
275 280 285
Asp Asp Leu Asn Ala Leu Leu Asn Glu Val Leu Lys Asn Gly Thr Leu
290 295 300
Thr Tyr Lys Gln Thr Lys Lys Leu Leu Gly Leu Ser Asp Asp Tyr Glu
305 310 315 320
Phe Lys Gly Glu Lys Gly Thr Tyr Phe Ile Glu Phe Lys Lys Tyr Lys
325 330 335
Glu Phe Ile Lys Ala Leu Gly Glu His Asn Leu Ser Gln Asp Asp Leu
340 345 350
Asn Glu Ile Ala Lys Asp Ile Thr Leu Ile Lys Asp Glu Ile Lys Leu
355 360 365
Lys Lys Ala Leu Ala Lys Tyr Asp Leu Asn Gln Asn Gln Ile Asp Ser
370 375 380
Leu Ser Lys Leu Glu Phe Lys Asp His Leu Asn Ile Ser Phe Lys Ala
385 390 395 400
Leu Lys Leu Val Thr Pro Leu Met Leu Glu Gly Lys Lys Tyr Asp Glu
405 410 415
Ala Cys Asn Glu Leu Asn Leu Lys Val Ala Ile Asn Glu Asp Lys Lys
420 425 430
Asp Phe Leu Pro Ala Phe Asn Glu Thr Tyr Tyr Lys Asp Glu Val Thr
435 440 445
Asn Pro Val Val Leu Arg Ala Ile Lys Glu Tyr Arg Lys Val Leu Asn
450 455 460
Ala Leu Leu Lys Lys Tyr Gly Lys Val His Lys Ile Asn Ile Glu Leu
465 470 475 480
Ala Arg Glu Val Gly Lys Asn His Ser Gln Arg Ala Lys Ile Glu Lys
485 490 495
Glu Gln Asn Glu Asn Tyr Lys Ala Lys Lys Asp Ala Glu Leu Glu Cys
500 505 510
Glu Lys Leu Gly Leu Lys Ile Asn Ser Lys Asn Ile Leu Lys Leu Arg
515 520 525
Leu Phe Lys Glu Gln Lys Glu Phe Cys Ala Tyr Ser Gly Glu Lys Ile
530 535 540
Lys Ile Ser Asp Leu Gln Asp Glu Lys Met Leu Glu Ile Asp His Ile
545 550 555 560
Tyr Pro Tyr Ser Arg Ser Phe Asp Asp Ser Tyr Met Asn Lys Val Leu
565 570 575
Val Phe Thr Lys Gln Asn Gln Glu Lys Leu Asn Gln Thr Pro Phe Glu
580 585 590
Ala Phe Gly Asn Asp Ser Ala Lys Trp Gln Lys Ile Glu Val Leu Ala
595 600 605
Lys Asn Leu Pro Thr Lys Lys Gln Lys Arg Ile Leu Asp Lys Asn Tyr
610 615 620
Lys Asp Lys Glu Gln Lys Asn Phe Lys Asp Arg Asn Leu Asn Asp Thr
625 630 635 640
Arg Tyr Ile Ala Arg Leu Val Leu Asn Tyr Thr Lys Asp Tyr Leu Asp
645 650 655
Phe Leu Pro Leu Ser Asp Asp Glu Asn Thr Lys Leu Asn Asp Thr Gln
660 665 670
Lys Gly Ser Lys Val His Val Glu Ala Lys Ser Gly Met Leu Thr Ser
675 680 685
Ala Leu Arg His Thr Trp Gly Phe Ser Ala Lys Asp Arg Asn Asn His
690 695 700
Leu His His Ala Ile Asp Ala Val Ile Ile Ala Tyr Ala Asn Asn Ser
705 710 715 720
Ile Val Lys Ala Phe Ser Asp Phe Lys Lys Glu Gln Glu Ser Asn Ser
725 730 735
Ala Glu Leu Tyr Ala Lys Lys Ile Ser Glu Leu Asp Tyr Lys Asn Lys
740 745 750
Arg Lys Phe Phe Glu Pro Phe Ser Gly Phe Arg Gln Lys Val Leu Asp
755 760 765
Lys Ile Asp Glu Ile Phe Val Ser Lys Pro Glu Arg Lys Lys Pro Ser
770 775 780
Gly Ala Leu His Glu Glu Thr Phe Arg Lys Glu Glu Glu Phe Tyr Gln
785 790 795 800
Ser Tyr Gly Gly Lys Glu Gly Val Leu Lys Ala Leu Glu Leu Gly Lys
805 810 815
Ile Arg Lys Val Asn Gly Lys Ile Val Lys Asn Gly Asp Met Phe Arg
820 825 830
Val Asp Ile Phe Lys His Lys Lys Thr Asn Lys Phe Tyr Ala Val Pro
835 840 845
Ile Tyr Thr Met Asp Phe Ala Leu Lys Val Leu Pro Asn Lys Ala Val
850 855 860
Ala Arg Ser Lys Lys Gly Glu Ile Lys Asp Trp Ile Leu Met Asp Glu
865 870 875 880
Asn Tyr Glu Phe Cys Phe Ser Leu Tyr Lys Asp Ser Leu Ile Leu Ile
885 890 895
Gln Thr Lys Asp Met Gln Glu Pro Glu Phe Val Tyr Tyr Asn Ala Phe
900 905 910
Thr Ser Ser Thr Val Ser Leu Ile Val Ser Lys His Asp Asn Lys Phe
915 920 925
Glu Thr Leu Ser Lys Asn Gln Lys Ile Leu Phe Lys Asn Ala Asn Glu
930 935 940
Lys Glu Val Ile Ala Lys Ser Ile Gly Ile Gln Asn Leu Lys Val Phe
945 950 955 960
Glu Lys Tyr Ile Val Ser Ala Leu Gly Glu Val Thr Lys Ala Glu Phe
965 970 975
Arg Gln Arg Glu Asp Phe Lys Lys
980
<210> 162
<211> 1056
<212> PRT
<213> 多杀巴斯德菌（Pasteurella multocida）
<400> 162
Met Gln Thr Thr Asn Leu Ser Tyr Ile Leu Gly Leu Asp Leu Gly Ile
1 5 10 15
Ala Ser Val Gly Trp Ala Val Val Glu Ile Asn Glu Asn Glu Asp Pro
20 25 30
Ile Gly Leu Ile Asp Val Gly Val Arg Ile Phe Glu Arg Ala Glu Val
35 40 45
Pro Lys Thr Gly Glu Ser Leu Ala Leu Ser Arg Arg Leu Ala Arg Ser
50 55 60
Thr Arg Arg Leu Ile Arg Arg Arg Ala His Arg Leu Leu Leu Ala Lys
65 70 75 80
Arg Phe Leu Lys Arg Glu Gly Ile Leu Ser Thr Ile Asp Leu Glu Lys
85 90 95
Gly Leu Pro Asn Gln Ala Trp Glu Leu Arg Val Ala Gly Leu Glu Arg
100 105 110
Arg Leu Ser Ala Ile Glu Trp Gly Ala Val Leu Leu His Leu Ile Lys
115 120 125
His Arg Gly Tyr Leu Ser Lys Arg Lys Asn Glu Ser Gln Thr Asn Asn
130 135 140
Lys Glu Leu Gly Ala Leu Leu Ser Gly Val Ala Gln Asn His Gln Leu
145 150 155 160
Leu Gln Ser Asp Asp Tyr Arg Thr Pro Ala Glu Leu Ala Leu Lys Lys
165 170 175
Phe Ala Lys Glu Glu Gly His Ile Arg Asn Gln Arg Gly Ala Tyr Thr
180 185 190
His Thr Phe Asn Arg Leu Asp Leu Leu Ala Glu Leu Asn Leu Leu Phe
195 200 205
Ala Gln Gln His Gln Phe Gly Asn Pro His Cys Lys Glu His Ile Gln
210 215 220
Gln Tyr Met Thr Glu Leu Leu Met Trp Gln Lys Pro Ala Leu Ser Gly
225 230 235 240
Glu Ala Ile Leu Lys Met Leu Gly Lys Cys Thr His Glu Lys Asn Glu
245 250 255
Phe Lys Ala Ala Lys His Thr Tyr Ser Ala Glu Arg Phe Val Trp Leu
260 265 270
Thr Lys Leu Asn Asn Leu Arg Ile Leu Glu Asp Gly Ala Glu Arg Ala
275 280 285
Leu Asn Glu Glu Glu Arg Gln Leu Leu Ile Asn His Pro Tyr Glu Lys
290 295 300
Ser Lys Leu Thr Tyr Ala Gln Val Arg Lys Leu Leu Gly Leu Ser Glu
305 310 315 320
Gln Ala Ile Phe Lys His Leu Arg Tyr Ser Lys Glu Asn Ala Glu Ser
325 330 335
Ala Thr Phe Met Glu Leu Lys Ala Trp His Ala Ile Arg Lys Ala Leu
340 345 350
Glu Asn Gln Gly Leu Lys Asp Thr Trp Gln Asp Leu Ala Lys Lys Pro
355 360 365
Asp Leu Leu Asp Glu Ile Gly Thr Ala Phe Ser Leu Tyr Lys Thr Asp
370 375 380
Glu Asp Ile Gln Gln Tyr Leu Thr Asn Lys Val Pro Asn Ser Val Ile
385 390 395 400
Asn Ala Leu Leu Val Ser Leu Asn Phe Asp Lys Phe Ile Glu Leu Ser
405 410 415
Leu Lys Ser Leu Arg Lys Ile Leu Pro Leu Met Glu Gln Gly Lys Arg
420 425 430
Tyr Asp Gln Ala Cys Arg Glu Ile Tyr Gly His His Tyr Gly Glu Ala
435 440 445
Asn Gln Lys Thr Ser Gln Leu Leu Pro Ala Ile Pro Ala Gln Glu Ile
450 455 460
Arg Asn Pro Val Val Leu Arg Thr Leu Ser Gln Ala Arg Lys Val Ile
465 470 475 480
Asn Ala Ile Ile Arg Gln Tyr Gly Ser Pro Ala Arg Val His Ile Glu
485 490 495
Thr Gly Arg Glu Leu Gly Lys Ser Phe Lys Glu Arg Arg Glu Ile Gln
500 505 510
Lys Gln Gln Glu Asp Asn Arg Thr Lys Arg Glu Ser Ala Val Gln Lys
515 520 525
Phe Lys Glu Leu Phe Ser Asp Phe Ser Ser Glu Pro Lys Ser Lys Asp
530 535 540
Ile Leu Lys Phe Arg Leu Tyr Glu Gln Gln His Gly Lys Cys Leu Tyr
545 550 555 560
Ser Gly Lys Glu Ile Asn Ile His Arg Leu Asn Glu Lys Gly Tyr Val
565 570 575
Glu Ile Asp His Ala Leu Pro Phe Ser Arg Thr Trp Asp Asp Ser Phe
580 585 590
Asn Asn Lys Val Leu Val Leu Ala Ser Glu Asn Gln Asn Lys Gly Asn
595 600 605
Gln Thr Pro Tyr Glu Trp Leu Gln Gly Lys Ile Asn Ser Glu Arg Trp
610 615 620
Lys Asn Phe Val Ala Leu Val Leu Gly Ser Gln Cys Ser Ala Ala Lys
625 630 635 640
Lys Gln Arg Leu Leu Thr Gln Val Ile Asp Asp Asn Lys Phe Ile Asp
645 650 655
Arg Asn Leu Asn Asp Thr Arg Tyr Ile Ala Arg Phe Leu Ser Asn Tyr
660 665 670
Ile Gln Glu Asn Leu Leu Leu Val Gly Lys Asn Lys Lys Asn Val Phe
675 680 685
Thr Pro Asn Gly Gln Ile Thr Ala Leu Leu Arg Ser Arg Trp Gly Leu
690 695 700
Ile Lys Ala Arg Glu Asn Asn Asn Arg His His Ala Leu Asp Ala Ile
705 710 715 720
Val Val Ala Cys Ala Thr Pro Ser Met Gln Gln Lys Ile Thr Arg Phe
725 730 735
Ile Arg Phe Lys Glu Val His Pro Tyr Lys Ile Glu Asn Arg Tyr Glu
740 745 750
Met Val Asp Gln Glu Ser Gly Glu Ile Ile Ser Pro His Phe Pro Glu
755 760 765
Pro Trp Ala Tyr Phe Arg Gln Glu Val Asn Ile Arg Val Phe Asp Asn
770 775 780
His Pro Asp Thr Val Leu Lys Glu Met Leu Pro Asp Arg Pro Gln Ala
785 790 795 800
Asn His Gln Phe Val Gln Pro Leu Phe Val Ser Arg Ala Pro Thr Arg
805 810 815
Lys Met Ser Gly Gln Gly His Met Glu Thr Ile Lys Ser Ala Lys Arg
820 825 830
Leu Ala Glu Gly Ile Ser Val Leu Arg Ile Pro Leu Thr Gln Leu Lys
835 840 845
Pro Asn Leu Leu Glu Asn Met Val Asn Lys Glu Arg Glu Pro Ala Leu
850 855 860
Tyr Ala Gly Leu Lys Ala Arg Leu Ala Glu Phe Asn Gln Asp Pro Ala
865 870 875 880
Lys Ala Phe Ala Thr Pro Phe Tyr Lys Gln Gly Gly Gln Gln Val Lys
885 890 895
Ala Ile Arg Val Glu Gln Val Gln Lys Ser Gly Val Leu Val Arg Glu
900 905 910
Asn Asn Gly Val Ala Asp Asn Ala Ser Ile Val Arg Thr Asp Val Phe
915 920 925
Ile Lys Asn Asn Lys Phe Phe Leu Val Pro Ile Tyr Thr Trp Gln Val
930 935 940
Ala Lys Gly Ile Leu Pro Asn Lys Ala Ile Val Ala His Lys Asn Glu
945 950 955 960
Asp Glu Trp Glu Glu Met Asp Glu Gly Ala Lys Phe Lys Phe Ser Leu
965 970 975
Phe Pro Asn Asp Leu Val Glu Leu Lys Thr Lys Lys Glu Tyr Phe Phe
980 985 990
Gly Tyr Tyr Ile Gly Leu Asp Arg Ala Thr Gly Asn Ile Ser Leu Lys
995 1000 1005
Glu His Asp Gly Glu Ile Ser Lys Gly Lys Asp Gly Val Tyr Arg
1010 1015 1020
Val Gly Val Lys Leu Ala Leu Ser Phe Glu Lys Tyr Gln Val Asp
1025 1030 1035
Glu Leu Gly Lys Asn Arg Gln Ile Cys Arg Pro Gln Gln Arg Gln
1040 1045 1050
Pro Val Arg
1055
<210> 163
<211> 1629
<212> PRT
<213> 新凶手弗朗西丝菌（Francisella novicida）
<400> 163
Met Asn Phe Lys Ile Leu Pro Ile Ala Ile Asp Leu Gly Val Lys Asn
1 5 10 15
Thr Gly Val Phe Ser Ala Phe Tyr Gln Lys Gly Thr Ser Leu Glu Arg
20 25 30
Leu Asp Asn Lys Asn Gly Lys Val Tyr Glu Leu Ser Lys Asp Ser Tyr
35 40 45
Thr Leu Leu Met Asn Asn Arg Thr Ala Arg Arg His Gln Arg Arg Gly
50 55 60
Ile Asp Arg Lys Gln Leu Val Lys Arg Leu Phe Lys Leu Ile Trp Thr
65 70 75 80
Glu Gln Leu Asn Leu Glu Trp Asp Lys Asp Thr Gln Gln Ala Ile Ser
85 90 95
Phe Leu Phe Asn Arg Arg Gly Phe Ser Phe Ile Thr Asp Gly Tyr Ser
100 105 110
Pro Glu Tyr Leu Asn Ile Val Pro Glu Gln Val Lys Ala Ile Leu Met
115 120 125
Asp Ile Phe Asp Asp Tyr Asn Gly Glu Asp Asp Leu Asp Ser Tyr Leu
130 135 140
Lys Leu Ala Thr Glu Gln Glu Ser Lys Ile Ser Glu Ile Tyr Asn Lys
145 150 155 160
Leu Met Gln Lys Ile Leu Glu Phe Lys Leu Met Lys Leu Cys Thr Asp
165 170 175
Ile Lys Asp Asp Lys Val Ser Thr Lys Thr Leu Lys Glu Ile Thr Ser
180 185 190
Tyr Glu Phe Glu Leu Leu Ala Asp Tyr Leu Ala Asn Tyr Ser Glu Ser
195 200 205
Leu Lys Thr Gln Lys Phe Ser Tyr Thr Asp Lys Gln Gly Asn Leu Lys
210 215 220
Glu Leu Ser Tyr Tyr His His Asp Lys Tyr Asn Ile Gln Glu Phe Leu
225 230 235 240
Lys Arg His Ala Thr Ile Asn Asp Arg Ile Leu Asp Thr Leu Leu Thr
245 250 255
Asp Asp Leu Asp Ile Trp Asn Phe Asn Phe Glu Lys Phe Asp Phe Asp
260 265 270
Lys Asn Glu Glu Lys Leu Gln Asn Gln Glu Asp Lys Asp His Ile Gln
275 280 285
Ala His Leu His His Phe Val Phe Ala Val Asn Lys Ile Lys Ser Glu
290 295 300
Met Ala Ser Gly Gly Arg His Arg Ser Gln Tyr Phe Gln Glu Ile Thr
305 310 315 320
Asn Val Leu Asp Glu Asn Asn His Gln Glu Gly Tyr Leu Lys Asn Phe
325 330 335
Cys Glu Asn Leu His Asn Lys Lys Tyr Ser Asn Leu Ser Val Lys Asn
340 345 350
Leu Val Asn Leu Ile Gly Asn Leu Ser Asn Leu Glu Leu Lys Pro Leu
355 360 365
Arg Lys Tyr Phe Asn Asp Lys Ile His Ala Lys Ala Asp His Trp Asp
370 375 380
Glu Gln Lys Phe Thr Glu Thr Tyr Cys His Trp Ile Leu Gly Glu Trp
385 390 395 400
Arg Val Gly Val Lys Asp Gln Asp Lys Lys Asp Gly Ala Lys Tyr Ser
405 410 415
Tyr Lys Asp Leu Cys Asn Glu Leu Lys Gln Lys Val Thr Lys Ala Gly
420 425 430
Leu Val Asp Phe Leu Leu Glu Leu Asp Pro Cys Arg Thr Ile Pro Pro
435 440 445
Tyr Leu Asp Asn Asn Asn Arg Lys Pro Pro Lys Cys Gln Ser Leu Ile
450 455 460
Leu Asn Pro Lys Phe Leu Asp Asn Gln Tyr Pro Asn Trp Gln Gln Tyr
465 470 475 480
Leu Gln Glu Leu Lys Lys Leu Gln Ser Ile Gln Asn Tyr Leu Asp Ser
485 490 495
Phe Glu Thr Asp Leu Lys Val Leu Lys Ser Ser Lys Asp Gln Pro Tyr
500 505 510
Phe Val Glu Tyr Lys Ser Ser Asn Gln Gln Ile Ala Ser Gly Gln Arg
515 520 525
Asp Tyr Lys Asp Leu Asp Ala Arg Ile Leu Gln Phe Ile Phe Asp Arg
530 535 540
Val Lys Ala Ser Asp Glu Leu Leu Leu Asn Glu Ile Tyr Phe Gln Ala
545 550 555 560
Lys Lys Leu Lys Gln Lys Ala Ser Ser Glu Leu Glu Lys Leu Glu Ser
565 570 575
Ser Lys Lys Leu Asp Glu Val Ile Ala Asn Ser Gln Leu Ser Gln Ile
580 585 590
Leu Lys Ser Gln His Thr Asn Gly Ile Phe Glu Gln Gly Thr Phe Leu
595 600 605
His Leu Val Cys Lys Tyr Tyr Lys Gln Arg Gln Arg Ala Arg Asp Ser
610 615 620
Arg Leu Tyr Ile Met Pro Glu Tyr Arg Tyr Asp Lys Lys Leu His Lys
625 630 635 640
Tyr Asn Asn Thr Gly Arg Phe Asp Asp Asp Asn Gln Leu Leu Thr Tyr
645 650 655
Cys Asn His Lys Pro Arg Gln Lys Arg Tyr Gln Leu Leu Asn Asp Leu
660 665 670
Ala Gly Val Leu Gln Val Ser Pro Asn Phe Leu Lys Asp Lys Ile Gly
675 680 685
Ser Asp Asp Asp Leu Phe Ile Ser Lys Trp Leu Val Glu His Ile Arg
690 695 700
Gly Phe Lys Lys Ala Cys Glu Asp Ser Leu Lys Ile Gln Lys Asp Asn
705 710 715 720
Arg Gly Leu Leu Asn His Lys Ile Asn Ile Ala Arg Asn Thr Lys Gly
725 730 735
Lys Cys Glu Lys Glu Ile Phe Asn Leu Ile Cys Lys Ile Glu Gly Ser
740 745 750
Glu Asp Lys Lys Gly Asn Tyr Lys His Gly Leu Ala Tyr Glu Leu Gly
755 760 765
Val Leu Leu Phe Gly Glu Pro Asn Glu Ala Ser Lys Pro Glu Phe Asp
770 775 780
Arg Lys Ile Lys Lys Phe Asn Ser Ile Tyr Ser Phe Ala Gln Ile Gln
785 790 795 800
Gln Ile Ala Phe Ala Glu Arg Lys Gly Asn Ala Asn Thr Cys Ala Val
805 810 815
Cys Ser Ala Asp Asn Ala His Arg Met Gln Gln Ile Lys Ile Thr Glu
820 825 830
Pro Val Glu Asp Asn Lys Asp Lys Ile Ile Leu Ser Ala Lys Ala Gln
835 840 845
Arg Leu Pro Ala Ile Pro Thr Arg Ile Val Asp Gly Ala Val Lys Lys
850 855 860
Met Ala Thr Ile Leu Ala Lys Asn Ile Val Asp Asp Asn Trp Gln Asn
865 870 875 880
Ile Lys Gln Val Leu Ser Ala Lys His Gln Leu His Ile Pro Ile Ile
885 890 895
Thr Glu Ser Asn Ala Phe Glu Phe Glu Pro Ala Leu Ala Asp Val Lys
900 905 910
Gly Lys Ser Leu Lys Asp Arg Arg Lys Lys Ala Leu Glu Arg Ile Ser
915 920 925
Pro Glu Asn Ile Phe Lys Asp Lys Asn Asn Arg Ile Lys Glu Phe Ala
930 935 940
Lys Gly Ile Ser Ala Tyr Ser Gly Ala Asn Leu Thr Asp Gly Asp Phe
945 950 955 960
Asp Gly Ala Lys Glu Glu Leu Asp His Ile Ile Pro Arg Ser His Lys
965 970 975
Lys Tyr Gly Thr Leu Asn Asp Glu Ala Asn Leu Ile Cys Val Thr Arg
980 985 990
Gly Asp Asn Lys Asn Lys Gly Asn Arg Ile Phe Cys Leu Arg Asp Leu
995 1000 1005
Ala Asp Asn Tyr Lys Leu Lys Gln Phe Glu Thr Thr Asp Asp Leu
1010 1015 1020
Glu Ile Glu Lys Lys Ile Ala Asp Thr Ile Trp Asp Ala Asn Lys
1025 1030 1035
Lys Asp Phe Lys Phe Gly Asn Tyr Arg Ser Phe Ile Asn Leu Thr
1040 1045 1050
Pro Gln Glu Gln Lys Ala Phe Arg His Ala Leu Phe Leu Ala Asp
1055 1060 1065
Glu Asn Pro Ile Lys Gln Ala Val Ile Arg Ala Ile Asn Asn Arg
1070 1075 1080
Asn Arg Thr Phe Val Asn Gly Thr Gln Arg Tyr Phe Ala Glu Val
1085 1090 1095
Leu Ala Asn Asn Ile Tyr Leu Arg Ala Lys Lys Glu Asn Leu Asn
1100 1105 1110
Thr Asp Lys Ile Ser Phe Asp Tyr Phe Gly Ile Pro Thr Ile Gly
1115 1120 1125
Asn Gly Arg Gly Ile Ala Glu Ile Arg Gln Leu Tyr Glu Lys Val
1130 1135 1140
Asp Ser Asp Ile Gln Ala Tyr Ala Lys Gly Asp Lys Pro Gln Ala
1145 1150 1155
Ser Tyr Ser His Leu Ile Asp Ala Met Leu Ala Phe Cys Ile Ala
1160 1165 1170
Ala Asp Glu His Arg Asn Asp Gly Ser Ile Gly Leu Glu Ile Asp
1175 1180 1185
Lys Asn Tyr Ser Leu Tyr Pro Leu Asp Lys Asn Thr Gly Glu Val
1190 1195 1200
Phe Thr Lys Asp Ile Phe Ser Gln Ile Lys Ile Thr Asp Asn Glu
1205 1210 1215
Phe Ser Asp Lys Lys Leu Val Arg Lys Lys Ala Ile Glu Gly Phe
1220 1225 1230
Asn Thr His Arg Gln Met Thr Arg Asp Gly Ile Tyr Ala Glu Asn
1235 1240 1245
Tyr Leu Pro Ile Leu Ile His Lys Glu Leu Asn Glu Val Arg Lys
1250 1255 1260
Gly Tyr Thr Trp Lys Asn Ser Glu Glu Ile Lys Ile Phe Lys Gly
1265 1270 1275
Lys Lys Tyr Asp Ile Gln Gln Leu Asn Asn Leu Val Tyr Cys Leu
1280 1285 1290
Lys Phe Val Asp Lys Pro Ile Ser Ile Asp Ile Gln Ile Ser Thr
1295 1300 1305
Leu Glu Glu Leu Arg Asn Ile Leu Thr Thr Asn Asn Ile Ala Ala
1310 1315 1320
Thr Ala Glu Tyr Tyr Tyr Ile Asn Leu Lys Thr Gln Lys Leu His
1325 1330 1335
Glu Tyr Tyr Ile Glu Asn Tyr Asn Thr Ala Leu Gly Tyr Lys Lys
1340 1345 1350
Tyr Ser Lys Glu Met Glu Phe Leu Arg Ser Leu Ala Tyr Arg Ser
1355 1360 1365
Glu Arg Val Lys Ile Lys Ser Ile Asp Asp Val Lys Gln Val Leu
1370 1375 1380
Asp Lys Asp Ser Asn Phe Ile Ile Gly Lys Ile Thr Leu Pro Phe
1385 1390 1395
Lys Lys Glu Trp Gln Arg Leu Tyr Arg Glu Trp Gln Asn Thr Thr
1400 1405 1410
Ile Lys Asp Asp Tyr Glu Phe Leu Lys Ser Phe Phe Asn Val Lys
1415 1420 1425
Ser Ile Thr Lys Leu His Lys Lys Val Arg Lys Asp Phe Ser Leu
1430 1435 1440
Pro Ile Ser Thr Asn Glu Gly Lys Phe Leu Val Lys Arg Lys Thr
1445 1450 1455
Trp Asp Asn Asn Phe Ile Tyr Gln Ile Leu Asn Asp Ser Asp Ser
1460 1465 1470
Arg Ala Asp Gly Thr Lys Pro Phe Ile Pro Ala Phe Asp Ile Ser
1475 1480 1485
Lys Asn Glu Ile Val Glu Ala Ile Ile Asp Ser Phe Thr Ser Lys
1490 1495 1500
Asn Ile Phe Trp Leu Pro Lys Asn Ile Glu Leu Gln Lys Val Asp
1505 1510 1515
Asn Lys Asn Ile Phe Ala Ile Asp Thr Ser Lys Trp Phe Glu Val
1520 1525 1530
Glu Thr Pro Ser Asp Leu Arg Asp Ile Gly Ile Ala Thr Ile Gln
1535 1540 1545
Tyr Lys Ile Asp Asn Asn Ser Arg Pro Lys Val Arg Val Lys Leu
1550 1555 1560
Asp Tyr Val Ile Asp Asp Asp Ser Lys Ile Asn Tyr Phe Met Asn
1565 1570 1575
His Ser Leu Leu Lys Ser Arg Tyr Pro Asp Lys Val Leu Glu Ile
1580 1585 1590
Leu Lys Gln Ser Thr Ile Ile Glu Phe Glu Ser Ser Gly Phe Asn
1595 1600 1605
Lys Thr Ile Lys Glu Met Leu Gly Met Lys Leu Ala Gly Ile Tyr
1610 1615 1620
Asn Glu Thr Ser Asn Asn
1625
<210> 164
<211> 1371
<212> PRT
<213> 布氏乳杆菌（Lactobacillus buchneri）
<400> 164
Met Lys Val Asn Asn Tyr His Ile Gly Leu Asp Ile Gly Thr Ser Ser
1 5 10 15
Ile Gly Trp Val Ala Ile Gly Lys Asp Gly Lys Pro Leu Arg Val Lys
20 25 30
Gly Lys Thr Ala Ile Gly Ala Arg Leu Phe Gln Glu Gly Asn Pro Ala
35 40 45
Ala Asp Arg Arg Met Phe Arg Thr Thr Arg Arg Arg Leu Ser Arg Arg
50 55 60
Lys Trp Arg Leu Lys Leu Leu Glu Glu Ile Phe Asp Pro Tyr Ile Thr
65 70 75 80
Pro Val Asp Ser Thr Phe Phe Ala Arg Leu Lys Gln Ser Asn Leu Ser
85 90 95
Pro Lys Asp Ser Arg Lys Glu Phe Lys Gly Ser Met Leu Phe Pro Asp
100 105 110
Leu Thr Asp Met Gln Tyr His Lys Asn Tyr Pro Thr Ile Tyr His Leu
115 120 125
Arg His Ala Leu Met Thr Gln Asp Lys Lys Phe Asp Ile Arg Met Val
130 135 140
Tyr Leu Ala Ile His His Ile Val Lys Tyr Arg Gly Asn Phe Leu Asn
145 150 155 160
Ser Thr Pro Val Asp Ser Phe Lys Ala Ser Lys Val Asp Phe Val Asp
165 170 175
Gln Phe Lys Lys Leu Asn Glu Leu Tyr Ala Ala Ile Asn Pro Glu Glu
180 185 190
Ser Phe Lys Ile Asn Leu Ala Asn Ser Glu Asp Ile Gly His Gln Phe
195 200 205
Leu Asp Pro Ser Ile Arg Lys Phe Asp Lys Lys Lys Gln Ile Pro Lys
210 215 220
Ile Val Pro Val Met Met Asn Asp Lys Val Thr Asp Arg Leu Asn Gly
225 230 235 240
Lys Ile Ala Ser Glu Ile Ile His Ala Ile Leu Gly Tyr Lys Ala Lys
245 250 255
Leu Asp Val Val Leu Gln Cys Thr Pro Val Asp Ser Lys Pro Trp Ala
260 265 270
Leu Lys Phe Asp Asp Glu Asp Ile Asp Ala Lys Leu Glu Lys Ile Leu
275 280 285
Pro Glu Met Asp Glu Asn Gln Gln Ser Ile Val Ala Ile Leu Gln Asn
290 295 300
Leu Tyr Ser Gln Val Thr Leu Asn Gln Ile Val Pro Asn Gly Met Ser
305 310 315 320
Leu Ser Glu Ser Met Ile Glu Lys Tyr Asn Asp His His Asp His Leu
325 330 335
Lys Leu Tyr Lys Lys Leu Ile Asp Gln Leu Ala Asp Pro Lys Lys Lys
340 345 350
Ala Val Leu Lys Lys Ala Tyr Ser Gln Tyr Val Gly Asp Asp Gly Lys
355 360 365
Val Ile Glu Gln Ala Glu Phe Trp Ser Ser Val Lys Lys Asn Leu Asp
370 375 380
Asp Ser Glu Leu Ser Lys Gln Ile Met Asp Leu Ile Asp Ala Glu Lys
385 390 395 400
Phe Met Pro Lys Gln Arg Thr Ser Gln Asn Gly Val Ile Pro His Gln
405 410 415
Leu His Gln Arg Glu Leu Asp Glu Ile Ile Glu His Gln Ser Lys Tyr
420 425 430
Tyr Pro Trp Leu Val Glu Ile Asn Pro Asn Lys His Asp Leu His Leu
435 440 445
Ala Lys Tyr Lys Ile Glu Gln Leu Val Ala Phe Arg Val Pro Tyr Tyr
450 455 460
Val Gly Pro Met Ile Thr Pro Lys Asp Gln Ala Glu Ser Ala Glu Thr
465 470 475 480
Val Phe Ser Trp Met Glu Arg Lys Gly Thr Glu Thr Gly Gln Ile Thr
485 490 495
Pro Trp Asn Phe Asp Glu Lys Val Asp Arg Lys Ala Ser Ala Asn Arg
500 505 510
Phe Ile Lys Arg Met Thr Thr Lys Asp Thr Tyr Leu Ile Gly Glu Asp
515 520 525
Val Leu Pro Asp Glu Ser Leu Leu Tyr Glu Lys Phe Lys Val Leu Asn
530 535 540
Glu Leu Asn Met Val Arg Val Asn Gly Lys Leu Leu Lys Val Ala Asp
545 550 555 560
Lys Gln Ala Ile Phe Gln Asp Leu Phe Glu Asn Tyr Lys His Val Ser
565 570 575
Val Lys Lys Leu Gln Asn Tyr Ile Lys Ala Lys Thr Gly Leu Pro Ser
580 585 590
Asp Pro Glu Ile Ser Gly Leu Ser Asp Pro Glu His Phe Asn Asn Ser
595 600 605
Leu Gly Thr Tyr Asn Asp Phe Lys Lys Leu Phe Gly Ser Lys Val Asp
610 615 620
Glu Pro Asp Leu Gln Asp Asp Phe Glu Lys Ile Val Glu Trp Ser Thr
625 630 635 640
Val Phe Glu Asp Lys Lys Ile Leu Arg Glu Lys Leu Asn Glu Ile Thr
645 650 655
Trp Leu Ser Asp Gln Gln Lys Asp Val Leu Glu Ser Ser Arg Tyr Gln
660 665 670
Gly Trp Gly Arg Leu Ser Lys Lys Leu Leu Thr Gly Ile Val Asn Asp
675 680 685
Gln Gly Glu Arg Ile Ile Asp Lys Leu Trp Asn Thr Asn Lys Asn Phe
690 695 700
Met Gln Ile Gln Ser Asp Asp Asp Phe Ala Lys Arg Ile His Glu Ala
705 710 715 720
Asn Ala Asp Gln Met Gln Ala Val Asp Val Glu Asp Val Leu Ala Asp
725 730 735
Ala Tyr Thr Ser Pro Gln Asn Lys Lys Ala Ile Arg Gln Val Val Lys
740 745 750
Val Val Asp Asp Ile Gln Lys Ala Met Gly Gly Val Ala Pro Lys Tyr
755 760 765
Ile Ser Ile Glu Phe Thr Arg Ser Glu Asp Arg Asn Pro Arg Arg Thr
770 775 780
Ile Ser Arg Gln Arg Gln Leu Glu Asn Thr Leu Lys Asp Thr Ala Lys
785 790 795 800
Ser Leu Ala Lys Ser Ile Asn Pro Glu Leu Leu Ser Glu Leu Asp Asn
805 810 815
Ala Ala Lys Ser Lys Lys Gly Leu Thr Asp Arg Leu Tyr Leu Tyr Phe
820 825 830
Thr Gln Leu Gly Lys Asp Ile Tyr Thr Gly Glu Pro Ile Asn Ile Asp
835 840 845
Glu Leu Asn Lys Tyr Asp Ile Asp His Ile Leu Pro Gln Ala Phe Ile
850 855 860
Lys Asp Asn Ser Leu Asp Asn Arg Val Leu Val Leu Thr Ala Val Asn
865 870 875 880
Asn Gly Lys Ser Asp Asn Val Pro Leu Arg Met Phe Gly Ala Lys Met
885 890 895
Gly His Phe Trp Lys Gln Leu Ala Glu Ala Gly Leu Ile Ser Lys Arg
900 905 910
Lys Leu Lys Asn Leu Gln Thr Asp Pro Asp Thr Ile Ser Lys Tyr Ala
915 920 925
Met His Gly Phe Ile Arg Arg Gln Leu Val Glu Thr Ser Gln Val Ile
930 935 940
Lys Leu Val Ala Asn Ile Leu Gly Asp Lys Tyr Arg Asn Asp Asp Thr
945 950 955 960
Lys Ile Ile Glu Ile Thr Ala Arg Met Asn His Gln Met Arg Asp Glu
965 970 975
Phe Gly Phe Ile Lys Asn Arg Glu Ile Asn Asp Tyr His His Ala Phe
980 985 990
Asp Ala Tyr Leu Thr Ala Phe Leu Gly Arg Tyr Leu Tyr His Arg Tyr
995 1000 1005
Ile Lys Leu Arg Pro Tyr Phe Val Tyr Gly Asp Phe Lys Lys Phe
1010 1015 1020
Arg Glu Asp Lys Val Thr Met Arg Asn Phe Asn Phe Leu His Asp
1025 1030 1035
Leu Thr Asp Asp Thr Gln Glu Lys Ile Ala Asp Ala Glu Thr Gly
1040 1045 1050
Glu Val Ile Trp Asp Arg Glu Asn Ser Ile Gln Gln Leu Lys Asp
1055 1060 1065
Val Tyr His Tyr Lys Phe Met Leu Ile Ser His Glu Val Tyr Thr
1070 1075 1080
Leu Arg Gly Ala Met Phe Asn Gln Thr Val Tyr Pro Ala Ser Asp
1085 1090 1095
Ala Gly Lys Arg Lys Leu Ile Pro Val Lys Ala Asp Arg Pro Val
1100 1105 1110
Asn Val Tyr Gly Gly Tyr Ser Gly Ser Ala Asp Ala Tyr Met Ala
1115 1120 1125
Ile Val Arg Ile His Asn Lys Lys Gly Asp Lys Tyr Arg Val Val
1130 1135 1140
Gly Val Pro Met Arg Ala Leu Asp Arg Leu Asp Ala Ala Lys Asn
1145 1150 1155
Val Ser Asp Ala Asp Phe Asp Arg Ala Leu Lys Asp Val Leu Ala
1160 1165 1170
Pro Gln Leu Thr Lys Thr Lys Lys Ser Arg Lys Thr Gly Glu Ile
1175 1180 1185
Thr Gln Val Ile Glu Asp Phe Glu Ile Val Leu Gly Lys Val Met
1190 1195 1200
Tyr Arg Gln Leu Met Ile Asp Gly Asp Lys Lys Phe Met Leu Gly
1205 1210 1215
Ser Ser Thr Tyr Gln Tyr Asn Ala Lys Gln Leu Val Leu Ser Asp
1220 1225 1230
Gln Ser Val Lys Thr Leu Ala Ser Lys Gly Arg Leu Asp Pro Leu
1235 1240 1245
Gln Glu Ser Met Asp Tyr Asn Asn Val Tyr Thr Glu Ile Leu Asp
1250 1255 1260
Lys Val Asn Gln Tyr Phe Ser Leu Tyr Asp Met Asn Lys Phe Arg
1265 1270 1275
His Lys Leu Asn Leu Gly Phe Ser Lys Phe Ile Ser Phe Pro Asn
1280 1285 1290
His Asn Val Leu Asp Gly Asn Thr Lys Val Ser Ser Gly Lys Arg
1295 1300 1305
Glu Ile Leu Gln Glu Ile Leu Asn Gly Leu His Ala Asn Pro Thr
1310 1315 1320
Phe Gly Asn Leu Lys Asp Val Gly Ile Thr Thr Pro Phe Gly Gln
1325 1330 1335
Leu Gln Gln Pro Asn Gly Ile Leu Leu Ser Asp Glu Thr Lys Ile
1340 1345 1350
Arg Tyr Gln Ser Pro Thr Gly Leu Phe Glu Arg Thr Val Ser Leu
1355 1360 1365
Lys Asp Leu
1370
<210> 165
<211> 1334
<212> PRT
<213> 无害李斯特菌（Listeria innocua）
<400> 165
Met Lys Lys Pro Tyr Thr Ile Gly Leu Asp Ile Gly Thr Asn Ser Val
1 5 10 15
Gly Trp Ala Val Leu Thr Asp Gln Tyr Asp Leu Val Lys Arg Lys Met
20 25 30
Lys Ile Ala Gly Asp Ser Glu Lys Lys Gln Ile Lys Lys Asn Phe Trp
35 40 45
Gly Val Arg Leu Phe Asp Glu Gly Gln Thr Ala Ala Asp Arg Arg Met
50 55 60
Ala Arg Thr Ala Arg Arg Arg Ile Glu Arg Arg Arg Asn Arg Ile Ser
65 70 75 80
Tyr Leu Gln Gly Ile Phe Ala Glu Glu Met Ser Lys Thr Asp Ala Asn
85 90 95
Phe Phe Cys Arg Leu Ser Asp Ser Phe Tyr Val Asp Asn Glu Lys Arg
100 105 110
Asn Ser Arg His Pro Phe Phe Ala Thr Ile Glu Glu Glu Val Glu Tyr
115 120 125
His Lys Asn Tyr Pro Thr Ile Tyr His Leu Arg Glu Glu Leu Val Asn
130 135 140
Ser Ser Glu Lys Ala Asp Leu Arg Leu Val Tyr Leu Ala Leu Ala His
145 150 155 160
Ile Ile Lys Tyr Arg Gly Asn Phe Leu Ile Glu Gly Ala Leu Asp Thr
165 170 175
Gln Asn Thr Ser Val Asp Gly Ile Tyr Lys Gln Phe Ile Gln Thr Tyr
180 185 190
Asn Gln Val Phe Ala Ser Gly Ile Glu Asp Gly Ser Leu Lys Lys Leu
195 200 205
Glu Asp Asn Lys Asp Val Ala Lys Ile Leu Val Glu Lys Val Thr Arg
210 215 220
Lys Glu Lys Leu Glu Arg Ile Leu Lys Leu Tyr Pro Gly Glu Lys Ser
225 230 235 240
Ala Gly Met Phe Ala Gln Phe Ile Ser Leu Ile Val Gly Ser Lys Gly
245 250 255
Asn Phe Gln Lys Pro Phe Asp Leu Ile Glu Lys Ser Asp Ile Glu Cys
260 265 270
Ala Lys Asp Ser Tyr Glu Glu Asp Leu Glu Ser Leu Leu Ala Leu Ile
275 280 285
Gly Asp Glu Tyr Ala Glu Leu Phe Val Ala Ala Lys Asn Ala Tyr Ser
290 295 300
Ala Val Val Leu Ser Ser Ile Ile Thr Val Ala Glu Thr Glu Thr Asn
305 310 315 320
Ala Lys Leu Ser Ala Ser Met Ile Glu Arg Phe Asp Thr His Glu Glu
325 330 335
Asp Leu Gly Glu Leu Lys Ala Phe Ile Lys Leu His Leu Pro Lys His
340 345 350
Tyr Glu Glu Ile Phe Ser Asn Thr Glu Lys His Gly Tyr Ala Gly Tyr
355 360 365
Ile Asp Gly Lys Thr Lys Gln Ala Asp Phe Tyr Lys Tyr Met Lys Met
370 375 380
Thr Leu Glu Asn Ile Glu Gly Ala Asp Tyr Phe Ile Ala Lys Ile Glu
385 390 395 400
Lys Glu Asn Phe Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ala Ile
405 410 415
Pro His Gln Leu His Leu Glu Glu Leu Glu Ala Ile Leu His Gln Gln
420 425 430
Ala Lys Tyr Tyr Pro Phe Leu Lys Glu Asn Tyr Asp Lys Ile Lys Ser
435 440 445
Leu Val Thr Phe Arg Ile Pro Tyr Phe Val Gly Pro Leu Ala Asn Gly
450 455 460
Gln Ser Glu Phe Ala Trp Leu Thr Arg Lys Ala Asp Gly Glu Ile Arg
465 470 475 480
Pro Trp Asn Ile Glu Glu Lys Val Asp Phe Gly Lys Ser Ala Val Asp
485 490 495
Phe Ile Glu Lys Met Thr Asn Lys Asp Thr Tyr Leu Pro Lys Glu Asn
500 505 510
Val Leu Pro Lys His Ser Leu Cys Tyr Gln Lys Tyr Leu Val Tyr Asn
515 520 525
Glu Leu Thr Lys Val Arg Tyr Ile Asn Asp Gln Gly Lys Thr Ser Tyr
530 535 540
Phe Ser Gly Gln Glu Lys Glu Gln Ile Phe Asn Asp Leu Phe Lys Gln
545 550 555 560
Lys Arg Lys Val Lys Lys Lys Asp Leu Glu Leu Phe Leu Arg Asn Met
565 570 575
Ser His Val Glu Ser Pro Thr Ile Glu Gly Leu Glu Asp Ser Phe Asn
580 585 590
Ser Ser Tyr Ser Thr Tyr His Asp Leu Leu Lys Val Gly Ile Lys Gln
595 600 605
Glu Ile Leu Asp Asn Pro Val Asn Thr Glu Met Leu Glu Asn Ile Val
610 615 620
Lys Ile Leu Thr Val Phe Glu Asp Lys Arg Met Ile Lys Glu Gln Leu
625 630 635 640
Gln Gln Phe Ser Asp Val Leu Asp Gly Val Val Leu Lys Lys Leu Glu
645 650 655
Arg Arg His Tyr Thr Gly Trp Gly Arg Leu Ser Ala Lys Leu Leu Met
660 665 670
Gly Ile Arg Asp Lys Gln Ser His Leu Thr Ile Leu Asp Tyr Leu Met
675 680 685
Asn Asp Asp Gly Leu Asn Arg Asn Leu Met Gln Leu Ile Asn Asp Ser
690 695 700
Asn Leu Ser Phe Lys Ser Ile Ile Glu Lys Glu Gln Val Thr Thr Ala
705 710 715 720
Asp Lys Asp Ile Gln Ser Ile Val Ala Asp Leu Ala Gly Ser Pro Ala
725 730 735
Ile Lys Lys Gly Ile Leu Gln Ser Leu Lys Ile Val Asp Glu Leu Val
740 745 750
Ser Val Met Gly Tyr Pro Pro Gln Thr Ile Val Val Glu Met Ala Arg
755 760 765
Glu Asn Gln Thr Thr Gly Lys Gly Lys Asn Asn Ser Arg Pro Arg Tyr
770 775 780
Lys Ser Leu Glu Lys Ala Ile Lys Glu Phe Gly Ser Gln Ile Leu Lys
785 790 795 800
Glu His Pro Thr Asp Asn Gln Glu Leu Arg Asn Asn Arg Leu Tyr Leu
805 810 815
Tyr Tyr Leu Gln Asn Gly Lys Asp Met Tyr Thr Gly Gln Asp Leu Asp
820 825 830
Ile His Asn Leu Ser Asn Tyr Asp Ile Asp His Ile Val Pro Gln Ser
835 840 845
Phe Ile Thr Asp Asn Ser Ile Asp Asn Leu Val Leu Thr Ser Ser Ala
850 855 860
Gly Asn Arg Glu Lys Gly Asp Asp Val Pro Pro Leu Glu Ile Val Arg
865 870 875 880
Lys Arg Lys Val Phe Trp Glu Lys Leu Tyr Gln Gly Asn Leu Met Ser
885 890 895
Lys Arg Lys Phe Asp Tyr Leu Thr Lys Ala Glu Arg Gly Gly Leu Thr
900 905 910
Glu Ala Asp Lys Ala Arg Phe Ile His Arg Gln Leu Val Glu Thr Arg
915 920 925
Gln Ile Thr Lys Asn Val Ala Asn Ile Leu His Gln Arg Phe Asn Tyr
930 935 940
Glu Lys Asp Asp His Gly Asn Thr Met Lys Gln Val Arg Ile Val Thr
945 950 955 960
Leu Lys Ser Ala Leu Val Ser Gln Phe Arg Lys Gln Phe Gln Leu Tyr
965 970 975
Lys Val Arg Asp Val Asn Asp Tyr His His Ala His Asp Ala Tyr Leu
980 985 990
Asn Gly Val Val Ala Asn Thr Leu Leu Lys Val Tyr Pro Gln Leu Glu
995 1000 1005
Pro Glu Phe Val Tyr Gly Asp Tyr His Gln Phe Asp Trp Phe Lys
1010 1015 1020
Ala Asn Lys Ala Thr Ala Lys Lys Gln Phe Tyr Thr Asn Ile Met
1025 1030 1035
Leu Phe Phe Ala Gln Lys Asp Arg Ile Ile Asp Glu Asn Gly Glu
1040 1045 1050
Ile Leu Trp Asp Lys Lys Tyr Leu Asp Thr Val Lys Lys Val Met
1055 1060 1065
Ser Tyr Arg Gln Met Asn Ile Val Lys Lys Thr Glu Ile Gln Lys
1070 1075 1080
Gly Glu Phe Ser Lys Ala Thr Ile Lys Pro Lys Gly Asn Ser Ser
1085 1090 1095
Lys Leu Ile Pro Arg Lys Thr Asn Trp Asp Pro Met Lys Tyr Gly
1100 1105 1110
Gly Leu Asp Ser Pro Asn Met Ala Tyr Ala Val Val Ile Glu Tyr
1115 1120 1125
Ala Lys Gly Lys Asn Lys Leu Val Phe Glu Lys Lys Ile Ile Arg
1130 1135 1140
Val Thr Ile Met Glu Arg Lys Ala Phe Glu Lys Asp Glu Lys Ala
1145 1150 1155
Phe Leu Glu Glu Gln Gly Tyr Arg Gln Pro Lys Val Leu Ala Lys
1160 1165 1170
Leu Pro Lys Tyr Thr Leu Tyr Glu Cys Glu Glu Gly Arg Arg Arg
1175 1180 1185
Met Leu Ala Ser Ala Asn Glu Ala Gln Lys Gly Asn Gln Gln Val
1190 1195 1200
Leu Pro Asn His Leu Val Thr Leu Leu His His Ala Ala Asn Cys
1205 1210 1215
Glu Val Ser Asp Gly Lys Ser Leu Asp Tyr Ile Glu Ser Asn Arg
1220 1225 1230
Glu Met Phe Ala Glu Leu Leu Ala His Val Ser Glu Phe Ala Lys
1235 1240 1245
Arg Tyr Thr Leu Ala Glu Ala Asn Leu Asn Lys Ile Asn Gln Leu
1250 1255 1260
Phe Glu Gln Asn Lys Glu Gly Asp Ile Lys Ala Ile Ala Gln Ser
1265 1270 1275
Phe Val Asp Leu Met Ala Phe Asn Ala Met Gly Ala Pro Ala Ser
1280 1285 1290
Phe Lys Phe Phe Glu Thr Thr Ile Glu Arg Lys Arg Tyr Asn Asn
1295 1300 1305
Leu Lys Glu Leu Leu Asn Ser Thr Ile Ile Tyr Gln Ser Ile Thr
1310 1315 1320
Gly Leu Tyr Glu Ser Arg Lys Arg Leu Asp Asp
1325 1330
<210> 166
<211> 1372
<212> PRT
<213> 嗜肺军团菌（Legionella pneumophila）
<400> 166
Met Glu Ser Ser Gln Ile Leu Ser Pro Ile Gly Ile Asp Leu Gly Gly
1 5 10 15
Lys Phe Thr Gly Val Cys Leu Ser His Leu Glu Ala Phe Ala Glu Leu
20 25 30
Pro Asn His Ala Asn Thr Lys Tyr Ser Val Ile Leu Ile Asp His Asn
35 40 45
Asn Phe Gln Leu Ser Gln Ala Gln Arg Arg Ala Thr Arg His Arg Val
50 55 60
Arg Asn Lys Lys Arg Asn Gln Phe Val Lys Arg Val Ala Leu Gln Leu
65 70 75 80
Phe Gln His Ile Leu Ser Arg Asp Leu Asn Ala Lys Glu Glu Thr Ala
85 90 95
Leu Cys His Tyr Leu Asn Asn Arg Gly Tyr Thr Tyr Val Asp Thr Asp
100 105 110
Leu Asp Glu Tyr Ile Lys Asp Glu Thr Thr Ile Asn Leu Leu Lys Glu
115 120 125
Leu Leu Pro Ser Glu Ser Glu His Asn Phe Ile Asp Trp Phe Leu Gln
130 135 140
Lys Met Gln Ser Ser Glu Phe Arg Lys Ile Leu Val Ser Lys Val Glu
145 150 155 160
Glu Lys Lys Asp Asp Lys Glu Leu Lys Asn Ala Val Lys Asn Ile Lys
165 170 175
Asn Phe Ile Thr Gly Phe Glu Lys Asn Ser Val Glu Gly His Arg His
180 185 190
Arg Lys Val Tyr Phe Glu Asn Ile Lys Ser Asp Ile Thr Lys Asp Asn
195 200 205
Gln Leu Asp Ser Ile Lys Lys Lys Ile Pro Ser Val Cys Leu Ser Asn
210 215 220
Leu Leu Gly His Leu Ser Asn Leu Gln Trp Lys Asn Leu His Arg Tyr
225 230 235 240
Leu Ala Lys Asn Pro Lys Gln Phe Asp Glu Gln Thr Phe Gly Asn Glu
245 250 255
Phe Leu Arg Met Leu Lys Asn Phe Arg His Leu Lys Gly Ser Gln Glu
260 265 270
Ser Leu Ala Val Arg Asn Leu Ile Gln Gln Leu Glu Gln Ser Gln Asp
275 280 285
Tyr Ile Ser Ile Leu Glu Lys Thr Pro Pro Glu Ile Thr Ile Pro Pro
290 295 300
Tyr Glu Ala Arg Thr Asn Thr Gly Met Glu Lys Asp Gln Ser Leu Leu
305 310 315 320
Leu Asn Pro Glu Lys Leu Asn Asn Leu Tyr Pro Asn Trp Arg Asn Leu
325 330 335
Ile Pro Gly Ile Ile Asp Ala His Pro Phe Leu Glu Lys Asp Leu Glu
340 345 350
His Thr Lys Leu Arg Asp Arg Lys Arg Ile Ile Ser Pro Ser Lys Gln
355 360 365
Asp Glu Lys Arg Asp Ser Tyr Ile Leu Gln Arg Tyr Leu Asp Leu Asn
370 375 380
Lys Lys Ile Asp Lys Phe Lys Ile Lys Lys Gln Leu Ser Phe Leu Gly
385 390 395 400
Gln Gly Lys Gln Leu Pro Ala Asn Leu Ile Glu Thr Gln Lys Glu Met
405 410 415
Glu Thr His Phe Asn Ser Ser Leu Val Ser Val Leu Ile Gln Ile Ala
420 425 430
Ser Ala Tyr Asn Lys Glu Arg Glu Asp Ala Ala Gln Gly Ile Trp Phe
435 440 445
Asp Asn Ala Phe Ser Leu Cys Glu Leu Ser Asn Ile Asn Pro Pro Arg
450 455 460
Lys Gln Lys Ile Leu Pro Leu Leu Val Gly Ala Ile Leu Ser Glu Asp
465 470 475 480
Phe Ile Asn Asn Lys Asp Lys Trp Ala Lys Phe Lys Ile Phe Trp Asn
485 490 495
Thr His Lys Ile Gly Arg Thr Ser Leu Lys Ser Lys Cys Lys Glu Ile
500 505 510
Glu Glu Ala Arg Lys Asn Ser Gly Asn Ala Phe Lys Ile Asp Tyr Glu
515 520 525
Glu Ala Leu Asn His Pro Glu His Ser Asn Asn Lys Ala Leu Ile Lys
530 535 540
Ile Ile Gln Thr Ile Pro Asp Ile Ile Gln Ala Ile Gln Ser His Leu
545 550 555 560
Gly His Asn Asp Ser Gln Ala Leu Ile Tyr His Asn Pro Phe Ser Leu
565 570 575
Ser Gln Leu Tyr Thr Ile Leu Glu Thr Lys Arg Asp Gly Phe His Lys
580 585 590
Asn Cys Val Ala Val Thr Cys Glu Asn Tyr Trp Arg Ser Gln Lys Thr
595 600 605
Glu Ile Asp Pro Glu Ile Ser Tyr Ala Ser Arg Leu Pro Ala Asp Ser
610 615 620
Val Arg Pro Phe Asp Gly Val Leu Ala Arg Met Met Gln Arg Leu Ala
625 630 635 640
Tyr Glu Ile Ala Met Ala Lys Trp Glu Gln Ile Lys His Ile Pro Asp
645 650 655
Asn Ser Ser Leu Leu Ile Pro Ile Tyr Leu Glu Gln Asn Arg Phe Glu
660 665 670
Phe Glu Glu Ser Phe Lys Lys Ile Lys Gly Ser Ser Ser Asp Lys Thr
675 680 685
Leu Glu Gln Ala Ile Glu Lys Gln Asn Ile Gln Trp Glu Glu Lys Phe
690 695 700
Gln Arg Ile Ile Asn Ala Ser Met Asn Ile Cys Pro Tyr Lys Gly Ala
705 710 715 720
Ser Ile Gly Gly Gln Gly Glu Ile Asp His Ile Tyr Pro Arg Ser Leu
725 730 735
Ser Lys Lys His Phe Gly Val Ile Phe Asn Ser Glu Val Asn Leu Ile
740 745 750
Tyr Cys Ser Ser Gln Gly Asn Arg Glu Lys Lys Glu Glu His Tyr Leu
755 760 765
Leu Glu His Leu Ser Pro Leu Tyr Leu Lys His Gln Phe Gly Thr Asp
770 775 780
Asn Val Ser Asp Ile Lys Asn Phe Ile Ser Gln Asn Val Ala Asn Ile
785 790 795 800
Lys Lys Tyr Ile Ser Phe His Leu Leu Thr Pro Glu Gln Gln Lys Ala
805 810 815
Ala Arg His Ala Leu Phe Leu Asp Tyr Asp Asp Glu Ala Phe Lys Thr
820 825 830
Ile Thr Lys Phe Leu Met Ser Gln Gln Lys Ala Arg Val Asn Gly Thr
835 840 845
Gln Lys Phe Leu Gly Lys Gln Ile Met Glu Phe Leu Ser Thr Leu Ala
850 855 860
Asp Ser Lys Gln Leu Gln Leu Glu Phe Ser Ile Lys Gln Ile Thr Ala
865 870 875 880
Glu Glu Val His Asp His Arg Glu Leu Leu Ser Lys Gln Glu Pro Lys
885 890 895
Leu Val Lys Ser Arg Gln Gln Ser Phe Pro Ser His Ala Ile Asp Ala
900 905 910
Thr Leu Thr Met Ser Ile Gly Leu Lys Glu Phe Pro Gln Phe Ser Gln
915 920 925
Glu Leu Asp Asn Ser Trp Phe Ile Asn His Leu Met Pro Asp Glu Val
930 935 940
His Leu Asn Pro Val Arg Ser Lys Glu Lys Tyr Asn Lys Pro Asn Ile
945 950 955 960
Ser Ser Thr Pro Leu Phe Lys Asp Ser Leu Tyr Ala Glu Arg Phe Ile
965 970 975
Pro Val Trp Val Lys Gly Glu Thr Phe Ala Ile Gly Phe Ser Glu Lys
980 985 990
Asp Leu Phe Glu Ile Lys Pro Ser Asn Lys Glu Lys Leu Phe Thr Leu
995 1000 1005
Leu Lys Thr Tyr Ser Thr Lys Asn Pro Gly Glu Ser Leu Gln Glu
1010 1015 1020
Leu Gln Ala Lys Ser Lys Ala Lys Trp Leu Tyr Phe Pro Ile Asn
1025 1030 1035
Lys Thr Leu Ala Leu Glu Phe Leu His His Tyr Phe His Lys Glu
1040 1045 1050
Ile Val Thr Pro Asp Asp Thr Thr Val Cys His Phe Ile Asn Ser
1055 1060 1065
Leu Arg Tyr Tyr Thr Lys Lys Glu Ser Ile Thr Val Lys Ile Leu
1070 1075 1080
Lys Glu Pro Met Pro Val Leu Ser Val Lys Phe Glu Ser Ser Lys
1085 1090 1095
Lys Asn Val Leu Gly Ser Phe Lys His Thr Ile Ala Leu Pro Ala
1100 1105 1110
Thr Lys Asp Trp Glu Arg Leu Phe Asn His Pro Asn Phe Leu Ala
1115 1120 1125
Leu Lys Ala Asn Pro Ala Pro Asn Pro Lys Glu Phe Asn Glu Phe
1130 1135 1140
Ile Arg Lys Tyr Phe Leu Ser Asp Asn Asn Pro Asn Ser Asp Ile
1145 1150 1155
Pro Asn Asn Gly His Asn Ile Lys Pro Gln Lys His Lys Ala Val
1160 1165 1170
Arg Lys Val Phe Ser Leu Pro Val Ile Pro Gly Asn Ala Gly Thr
1175 1180 1185
Met Met Arg Ile Arg Arg Lys Asp Asn Lys Gly Gln Pro Leu Tyr
1190 1195 1200
Gln Leu Gln Thr Ile Asp Asp Thr Pro Ser Met Gly Ile Gln Ile
1205 1210 1215
Asn Glu Asp Arg Leu Val Lys Gln Glu Val Leu Met Asp Ala Tyr
1220 1225 1230
Lys Thr Arg Asn Leu Ser Thr Ile Asp Gly Ile Asn Asn Ser Glu
1235 1240 1245
Gly Gln Ala Tyr Ala Thr Phe Asp Asn Trp Leu Thr Leu Pro Val
1250 1255 1260
Ser Thr Phe Lys Pro Glu Ile Ile Lys Leu Glu Met Lys Pro His
1265 1270 1275
Ser Lys Thr Arg Arg Tyr Ile Arg Ile Thr Gln Ser Leu Ala Asp
1280 1285 1290
Phe Ile Lys Thr Ile Asp Glu Ala Leu Met Ile Lys Pro Ser Asp
1295 1300 1305
Ser Ile Asp Asp Pro Leu Asn Met Pro Asn Glu Ile Val Cys Lys
1310 1315 1320
Asn Lys Leu Phe Gly Asn Glu Leu Lys Pro Arg Asp Gly Lys Met
1325 1330 1335
Lys Ile Val Ser Thr Gly Lys Ile Val Thr Tyr Glu Phe Glu Ser
1340 1345 1350
Asp Ser Thr Pro Gln Trp Ile Gln Thr Leu Tyr Val Thr Gln Leu
1355 1360 1365
Lys Lys Gln Pro
1370
<210> 167
<211> 1082
<212> PRT
<213> 嗜乳糖奈瑟球菌（Neisseria lactamica）
<400> 167
Met Ala Ala Phe Lys Pro Asn Pro Met Asn Tyr Ile Leu Gly Leu Asp
1 5 10 15
Ile Gly Ile Ala Ser Val Gly Trp Ala Met Val Glu Val Asp Glu Glu
20 25 30
Glu Asn Pro Ile Arg Leu Ile Asp Leu Gly Val Arg Val Phe Glu Arg
35 40 45
Ala Glu Val Pro Lys Thr Gly Asp Ser Leu Ala Met Ala Arg Arg Leu
50 55 60
Ala Arg Ser Val Arg Arg Leu Thr Arg Arg Arg Ala His Arg Leu Leu
65 70 75 80
Arg Ala Arg Arg Leu Leu Lys Arg Glu Gly Val Leu Gln Asp Ala Asp
85 90 95
Phe Asp Glu Asn Gly Leu Val Lys Ser Leu Pro Asn Thr Pro Trp Gln
100 105 110
Leu Arg Ala Ala Ala Leu Asp Arg Lys Leu Thr Cys Leu Glu Trp Ser
115 120 125
Ala Val Leu Leu His Leu Val Lys His Arg Gly Tyr Leu Ser Gln Arg
130 135 140
Lys Asn Glu Gly Glu Thr Ala Asp Lys Glu Leu Gly Ala Leu Leu Lys
145 150 155 160
Gly Val Ala Asp Asn Ala His Ala Leu Gln Thr Gly Asp Phe Arg Thr
165 170 175
Pro Ala Glu Leu Ala Leu Asn Lys Phe Glu Lys Glu Ser Gly His Ile
180 185 190
Arg Asn Gln Arg Gly Asp Tyr Ser His Thr Phe Ser Arg Lys Asp Leu
195 200 205
Gln Ala Glu Leu Asn Leu Leu Phe Glu Lys Gln Lys Glu Phe Gly Asn
210 215 220
Pro His Val Ser Asp Gly Leu Lys Glu Asp Ile Glu Thr Leu Leu Met
225 230 235 240
Ala Gln Arg Pro Ala Leu Ser Gly Asp Ala Val Gln Lys Met Leu Gly
245 250 255
His Cys Thr Phe Glu Pro Ala Glu Pro Lys Ala Ala Lys Asn Thr Tyr
260 265 270
Thr Ala Glu Arg Phe Ile Trp Leu Thr Lys Leu Asn Asn Leu Arg Ile
275 280 285
Leu Glu Gln Gly Ser Glu Arg Pro Leu Thr Asp Thr Glu Arg Ala Thr
290 295 300
Leu Met Asp Glu Pro Tyr Arg Lys Ser Lys Leu Thr Tyr Ala Gln Ala
305 310 315 320
Arg Lys Leu Leu Gly Leu Glu Asp Thr Ala Phe Phe Lys Gly Leu Arg
325 330 335
Tyr Gly Lys Asp Asn Ala Glu Ala Ser Thr Leu Met Glu Met Lys Ala
340 345 350
Tyr His Ala Ile Ser Arg Ala Leu Glu Lys Glu Gly Leu Lys Asp Lys
355 360 365
Lys Ser Pro Leu Asn Leu Ser Thr Glu Leu Gln Asp Glu Ile Gly Thr
370 375 380
Ala Phe Ser Leu Phe Lys Thr Asp Lys Asp Ile Thr Gly Arg Leu Lys
385 390 395 400
Asp Arg Val Gln Pro Glu Ile Leu Glu Ala Leu Leu Lys His Ile Ser
405 410 415
Phe Asp Lys Phe Val Gln Ile Ser Leu Lys Ala Leu Arg Arg Ile Val
420 425 430
Pro Leu Met Glu Gln Gly Lys Arg Tyr Asp Glu Ala Cys Ala Glu Ile
435 440 445
Tyr Gly Asp His Tyr Cys Lys Lys Asn Ala Glu Glu Lys Ile Tyr Leu
450 455 460
Pro Pro Ile Pro Ala Asp Glu Ile Arg Asn Pro Val Val Leu Arg Ala
465 470 475 480
Leu Ser Gln Ala Arg Lys Val Ile Asn Cys Val Val Arg Arg Tyr Gly
485 490 495
Ser Pro Ala Arg Ile His Ile Glu Thr Ala Arg Glu Val Gly Lys Ser
500 505 510
Phe Lys Asp Arg Lys Glu Ile Glu Lys Arg Gln Glu Glu Asn Arg Lys
515 520 525
Asp Arg Glu Lys Ala Ala Ala Lys Phe Arg Glu Tyr Phe Pro Asn Phe
530 535 540
Val Gly Glu Pro Lys Ser Lys Asp Ile Leu Lys Leu Arg Leu Tyr Glu
545 550 555 560
Gln Gln His Gly Lys Cys Leu Tyr Ser Gly Lys Glu Ile Asn Leu Val
565 570 575
Arg Leu Asn Glu Lys Gly Tyr Val Glu Ile Asp His Ala Leu Pro Phe
580 585 590
Ser Arg Thr Trp Asp Asp Ser Phe Asn Asn Lys Val Leu Val Leu Gly
595 600 605
Ser Glu Asn Gln Asn Lys Gly Asn Gln Thr Pro Tyr Glu Tyr Phe Asn
610 615 620
Gly Lys Asp Asn Ser Arg Glu Trp Gln Glu Phe Lys Ala Arg Val Glu
625 630 635 640
Thr Ser Arg Phe Pro Arg Ser Lys Lys Gln Arg Ile Leu Leu Gln Lys
645 650 655
Phe Asp Glu Glu Gly Phe Lys Glu Arg Asn Leu Asn Asp Thr Arg Tyr
660 665 670
Val Asn Arg Phe Leu Cys Gln Phe Val Ala Asp His Ile Leu Leu Thr
675 680 685
Gly Lys Gly Lys Arg Arg Val Phe Ala Ser Asn Gly Gln Ile Thr Asn
690 695 700
Leu Leu Arg Gly Phe Trp Gly Leu Arg Lys Val Arg Thr Glu Asn Asp
705 710 715 720
Arg His His Ala Leu Asp Ala Val Val Val Ala Cys Ser Thr Val Ala
725 730 735
Met Gln Gln Lys Ile Thr Arg Phe Val Arg Tyr Lys Glu Met Asn Ala
740 745 750
Phe Asp Gly Lys Thr Ile Asp Lys Glu Thr Gly Glu Val Leu His Gln
755 760 765
Lys Ala His Phe Pro Gln Pro Trp Glu Phe Phe Ala Gln Glu Val Met
770 775 780
Ile Arg Val Phe Gly Lys Pro Asp Gly Lys Pro Glu Phe Glu Glu Ala
785 790 795 800
Asp Thr Pro Glu Lys Leu Arg Thr Leu Leu Ala Glu Lys Leu Ser Ser
805 810 815
Arg Pro Glu Ala Val His Glu Tyr Val Thr Pro Leu Phe Val Ser Arg
820 825 830
Ala Pro Asn Arg Lys Met Ser Gly Gln Gly His Met Glu Thr Val Lys
835 840 845
Ser Ala Lys Arg Leu Asp Glu Gly Ile Ser Val Leu Arg Val Pro Leu
850 855 860
Thr Gln Leu Lys Leu Lys Gly Leu Glu Lys Met Val Asn Arg Glu Arg
865 870 875 880
Glu Pro Lys Leu Tyr Asp Ala Leu Lys Ala Gln Leu Glu Thr His Lys
885 890 895
Asp Asp Pro Ala Lys Ala Phe Ala Glu Pro Phe Tyr Lys Tyr Asp Lys
900 905 910
Ala Gly Ser Arg Thr Gln Gln Val Lys Ala Val Arg Ile Glu Gln Val
915 920 925
Gln Lys Thr Gly Val Trp Val Arg Asn His Asn Gly Ile Ala Asp Asn
930 935 940
Ala Thr Met Val Arg Val Asp Val Phe Glu Lys Gly Gly Lys Tyr Tyr
945 950 955 960
Leu Val Pro Ile Tyr Ser Trp Gln Val Ala Lys Gly Ile Leu Pro Asp
965 970 975
Arg Ala Val Val Ala Phe Lys Asp Glu Glu Asp Trp Thr Val Met Asp
980 985 990
Asp Ser Phe Glu Phe Arg Phe Val Leu Tyr Ala Asn Asp Leu Ile Lys
995 1000 1005
Leu Thr Ala Lys Lys Asn Glu Phe Leu Gly Tyr Phe Val Ser Leu
1010 1015 1020
Asn Arg Ala Thr Gly Ala Ile Asp Ile Arg Thr His Asp Thr Asp
1025 1030 1035
Ser Thr Lys Gly Lys Asn Gly Ile Phe Gln Ser Val Gly Val Lys
1040 1045 1050
Thr Ala Leu Ser Phe Gln Lys Asn Gln Ile Asp Glu Leu Gly Lys
1055 1060 1065
Glu Ile Arg Pro Cys Arg Leu Lys Lys Arg Pro Pro Val Arg
1070 1075 1080
<210> 168
<211> 1082
<212> PRT
<213> 脑膜炎奈瑟球菌（Neisseria meningitidis）
<400> 168
Met Ala Ala Phe Lys Pro Asn Pro Ile Asn Tyr Ile Leu Gly Leu Asp
1 5 10 15
Ile Gly Ile Ala Ser Val Gly Trp Ala Met Val Glu Ile Asp Glu Asp
20 25 30
Glu Asn Pro Ile Cys Leu Ile Asp Leu Gly Val Arg Val Phe Glu Arg
35 40 45
Ala Glu Val Pro Lys Thr Gly Asp Ser Leu Ala Met Ala Arg Arg Leu
50 55 60
Ala Arg Ser Val Arg Arg Leu Thr Arg Arg Arg Ala His Arg Leu Leu
65 70 75 80
Arg Ala Arg Arg Leu Leu Lys Arg Glu Gly Val Leu Gln Ala Ala Asp
85 90 95
Phe Asp Glu Asn Gly Leu Ile Lys Ser Leu Pro Asn Thr Pro Trp Gln
100 105 110
Leu Arg Ala Ala Ala Leu Asp Arg Lys Leu Thr Pro Leu Glu Trp Ser
115 120 125
Ala Val Leu Leu His Leu Ile Lys His Arg Gly Tyr Leu Ser Gln Arg
130 135 140
Lys Asn Glu Gly Glu Thr Ala Asp Lys Glu Leu Gly Ala Leu Leu Lys
145 150 155 160
Gly Val Ala Asp Asn Ala His Ala Leu Gln Thr Gly Asp Phe Arg Thr
165 170 175
Pro Ala Glu Leu Ala Leu Asn Lys Phe Glu Lys Glu Ser Gly His Ile
180 185 190
Arg Asn Gln Arg Gly Asp Tyr Ser His Thr Phe Ser Arg Lys Asp Leu
195 200 205
Gln Ala Glu Leu Ile Leu Leu Phe Glu Lys Gln Lys Glu Phe Gly Asn
210 215 220
Pro His Val Ser Gly Gly Leu Lys Glu Gly Ile Glu Thr Leu Leu Met
225 230 235 240
Thr Gln Arg Pro Ala Leu Ser Gly Asp Ala Val Gln Lys Met Leu Gly
245 250 255
His Cys Thr Phe Glu Pro Ala Glu Pro Lys Ala Ala Lys Asn Thr Tyr
260 265 270
Thr Ala Glu Arg Phe Ile Trp Leu Thr Lys Leu Asn Asn Leu Arg Ile
275 280 285
Leu Glu Gln Gly Ser Glu Arg Pro Leu Thr Asp Thr Glu Arg Ala Thr
290 295 300
Leu Met Asp Glu Pro Tyr Arg Lys Ser Lys Leu Thr Tyr Ala Gln Ala
305 310 315 320
Arg Lys Leu Leu Gly Leu Glu Asp Thr Ala Phe Phe Lys Gly Leu Arg
325 330 335
Tyr Gly Lys Asp Asn Ala Glu Ala Ser Thr Leu Met Glu Met Lys Ala
340 345 350
Tyr His Ala Ile Ser Arg Ala Leu Glu Lys Glu Gly Leu Lys Asp Lys
355 360 365
Lys Ser Pro Leu Asn Leu Ser Pro Glu Leu Gln Asp Glu Ile Gly Thr
370 375 380
Ala Phe Ser Leu Phe Lys Thr Asp Glu Asp Ile Thr Gly Arg Leu Lys
385 390 395 400
Asp Arg Ile Gln Pro Glu Ile Leu Glu Ala Leu Leu Lys His Ile Ser
405 410 415
Phe Asp Lys Phe Val Gln Ile Ser Leu Lys Ala Leu Arg Arg Ile Val
420 425 430
Pro Leu Met Glu Gln Gly Lys Arg Tyr Asp Glu Ala Cys Ala Glu Ile
435 440 445
Tyr Gly Asp His Tyr Gly Lys Lys Asn Thr Glu Glu Lys Ile Tyr Leu
450 455 460
Pro Pro Ile Pro Ala Asp Glu Ile Arg Asn Pro Val Val Leu Arg Ala
465 470 475 480
Leu Ser Gln Ala Arg Lys Val Ile Asn Gly Val Val Arg Arg Tyr Gly
485 490 495
Ser Pro Ala Arg Ile His Ile Glu Thr Ala Arg Glu Val Gly Lys Ser
500 505 510
Phe Lys Asp Arg Lys Glu Ile Glu Lys Arg Gln Glu Glu Asn Arg Lys
515 520 525
Asp Arg Glu Lys Ala Ala Ala Lys Phe Arg Glu Tyr Phe Pro Asn Phe
530 535 540
Val Gly Glu Pro Lys Ser Lys Asp Ile Leu Lys Leu Arg Leu Tyr Glu
545 550 555 560
Gln Gln His Gly Lys Cys Leu Tyr Ser Gly Lys Glu Ile Asn Leu Gly
565 570 575
Arg Leu Asn Glu Lys Gly Tyr Val Glu Ile Asp His Ala Leu Pro Phe
580 585 590
Ser Arg Thr Trp Asp Asp Ser Phe Asn Asn Lys Val Leu Val Leu Gly
595 600 605
Ser Glu Asn Gln Asn Lys Gly Asn Gln Thr Pro Tyr Glu Tyr Phe Asn
610 615 620
Gly Lys Asp Asn Ser Arg Glu Trp Gln Glu Phe Lys Ala Arg Val Glu
625 630 635 640
Thr Ser Arg Phe Pro Arg Ser Lys Lys Gln Arg Ile Leu Leu Gln Lys
645 650 655
Phe Asp Glu Asp Gly Phe Lys Glu Arg Asn Leu Asn Asp Thr Arg Tyr
660 665 670
Val Asn Arg Phe Leu Cys Gln Phe Val Ala Asp Arg Met Arg Leu Thr
675 680 685
Gly Lys Gly Lys Lys Arg Val Phe Ala Ser Asn Gly Gln Ile Thr Asn
690 695 700
Leu Leu Arg Gly Phe Trp Gly Leu Arg Lys Val Arg Ala Glu Asn Asp
705 710 715 720
Arg His His Ala Leu Asp Ala Val Val Val Ala Cys Ser Thr Val Ala
725 730 735
Met Gln Gln Lys Ile Thr Arg Phe Val Arg Tyr Lys Glu Met Asn Ala
740 745 750
Phe Asp Gly Lys Thr Ile Asp Lys Glu Thr Gly Glu Val Leu His Gln
755 760 765
Lys Thr His Phe Pro Gln Pro Trp Glu Phe Phe Ala Gln Glu Val Met
770 775 780
Ile Arg Val Phe Gly Lys Pro Asp Gly Lys Pro Glu Phe Glu Glu Ala
785 790 795 800
Asp Thr Pro Glu Lys Leu Arg Thr Leu Leu Ala Glu Lys Leu Ser Ser
805 810 815
Arg Pro Glu Ala Val His Glu Tyr Val Thr Pro Leu Phe Val Ser Arg
820 825 830
Ala Pro Asn Arg Lys Met Ser Gly Gln Gly His Met Glu Thr Val Lys
835 840 845
Ser Ala Lys Arg Leu Asp Glu Gly Val Ser Val Leu Arg Val Pro Leu
850 855 860
Thr Gln Leu Lys Leu Lys Asp Leu Glu Lys Met Val Asn Arg Glu Arg
865 870 875 880
Glu Pro Lys Leu Tyr Glu Ala Leu Lys Ala Arg Leu Glu Ala His Lys
885 890 895
Asp Asp Pro Ala Lys Ala Phe Ala Glu Pro Phe Tyr Lys Tyr Asp Lys
900 905 910
Ala Gly Asn Arg Thr Gln Gln Val Lys Ala Val Arg Val Glu Gln Val
915 920 925
Gln Lys Thr Gly Val Trp Val Arg Asn His Asn Gly Ile Ala Asp Asn
930 935 940
Ala Thr Met Val Arg Val Asp Val Phe Glu Lys Gly Asp Lys Tyr Tyr
945 950 955 960
Leu Val Pro Ile Tyr Ser Trp Gln Val Ala Lys Gly Ile Leu Pro Asp
965 970 975
Arg Ala Val Val Gln Gly Lys Asp Glu Glu Asp Trp Gln Leu Ile Asp
980 985 990
Asp Ser Phe Asn Phe Lys Phe Ser Leu His Pro Asn Asp Leu Val Glu
995 1000 1005
Val Ile Thr Lys Lys Ala Arg Met Phe Gly Tyr Phe Ala Ser Cys
1010 1015 1020
His Arg Gly Thr Gly Asn Ile Asn Ile Arg Ile His Asp Leu Asp
1025 1030 1035
His Lys Ile Gly Lys Asn Gly Ile Leu Glu Gly Ile Gly Val Lys
1040 1045 1050
Thr Ala Leu Ser Phe Gln Lys Tyr Gln Ile Asp Glu Leu Gly Lys
1055 1060 1065
Glu Ile Arg Pro Cys Arg Leu Lys Lys Arg Pro Pro Val Arg
1070 1075 1080
<210> 169
<211> 1187
<212> PRT
<213> 长双歧杆菌（Bifidobacterium longum）
<400> 169
Met Leu Ser Arg Gln Leu Leu Gly Ala Ser His Leu Ala Arg Pro Val
1 5 10 15
Ser Tyr Ser Tyr Asn Val Gln Asp Asn Asp Val His Cys Ser Tyr Gly
20 25 30
Glu Arg Cys Phe Met Arg Gly Lys Arg Tyr Arg Ile Gly Ile Asp Val
35 40 45
Gly Leu Asn Ser Val Gly Leu Ala Ala Val Glu Val Ser Asp Glu Asn
50 55 60
Ser Pro Val Arg Leu Leu Asn Ala Gln Ser Val Ile His Asp Gly Gly
65 70 75 80
Val Asp Pro Gln Lys Asn Lys Glu Ala Ile Thr Arg Lys Asn Met Ser
85 90 95
Gly Val Ala Arg Arg Thr Arg Arg Met Arg Arg Arg Lys Arg Glu Arg
100 105 110
Leu His Lys Leu Asp Met Leu Leu Gly Lys Phe Gly Tyr Pro Val Ile
115 120 125
Glu Pro Glu Ser Leu Asp Lys Pro Phe Glu Glu Trp His Val Arg Ala
130 135 140
Glu Leu Ala Thr Arg Tyr Ile Glu Asp Asp Glu Leu Arg Arg Glu Ser
145 150 155 160
Ile Ser Ile Ala Leu Arg His Met Ala Arg His Arg Gly Trp Arg Asn
165 170 175
Pro Tyr Arg Gln Val Asp Ser Leu Ile Ser Asp Asn Pro Tyr Ser Lys
180 185 190
Gln Tyr Gly Glu Leu Lys Glu Lys Ala Lys Ala Tyr Asn Asp Asp Ala
195 200 205
Thr Ala Ala Glu Glu Glu Ser Thr Pro Ala Gln Leu Val Val Ala Met
210 215 220
Leu Asp Ala Gly Tyr Ala Glu Ala Pro Arg Leu Arg Trp Arg Thr Gly
225 230 235 240
Ser Lys Lys Pro Asp Ala Glu Gly Tyr Leu Pro Val Arg Leu Met Gln
245 250 255
Glu Asp Asn Ala Asn Glu Leu Lys Gln Ile Phe Arg Val Gln Arg Val
260 265 270
Pro Ala Asp Glu Trp Lys Pro Leu Phe Arg Ser Val Phe Tyr Ala Val
275 280 285
Ser Pro Lys Gly Ser Ala Glu Gln Arg Val Gly Gln Asp Pro Leu Ala
290 295 300
Pro Glu Gln Ala Arg Ala Leu Lys Ala Ser Leu Ala Phe Gln Glu Tyr
305 310 315 320
Arg Ile Ala Asn Val Ile Thr Asn Leu Arg Ile Lys Asp Ala Ser Ala
325 330 335
Glu Leu Arg Lys Leu Thr Val Asp Glu Lys Gln Ser Ile Tyr Asp Gln
340 345 350
Leu Val Ser Pro Ser Ser Glu Asp Ile Thr Trp Ser Asp Leu Cys Asp
355 360 365
Phe Leu Gly Phe Lys Arg Ser Gln Leu Lys Gly Val Gly Ser Leu Thr
370 375 380
Glu Asp Gly Glu Glu Arg Ile Ser Ser Arg Pro Pro Arg Leu Thr Ser
385 390 395 400
Val Gln Arg Ile Tyr Glu Ser Asp Asn Lys Ile Arg Lys Pro Leu Val
405 410 415
Ala Trp Trp Lys Ser Ala Ser Asp Asn Glu His Glu Ala Met Ile Arg
420 425 430
Leu Leu Ser Asn Thr Val Asp Ile Asp Lys Val Arg Glu Asp Val Ala
435 440 445
Tyr Ala Ser Ala Ile Glu Phe Ile Asp Gly Leu Asp Asp Asp Ala Leu
450 455 460
Thr Lys Leu Asp Ser Val Asp Leu Pro Ser Gly Arg Ala Ala Tyr Ser
465 470 475 480
Val Glu Thr Leu Gln Lys Leu Thr Arg Gln Met Leu Thr Thr Asp Asp
485 490 495
Asp Leu His Glu Ala Arg Lys Thr Leu Phe Asn Val Thr Asp Ser Trp
500 505 510
Arg Pro Pro Ala Asp Pro Ile Gly Glu Pro Leu Gly Asn Pro Ser Val
515 520 525
Asp Arg Val Leu Lys Asn Val Asn Arg Tyr Leu Met Asn Cys Gln Gln
530 535 540
Arg Trp Gly Asn Pro Val Ser Val Asn Ile Glu His Val Arg Ser Ser
545 550 555 560
Phe Ser Ser Val Ala Phe Ala Arg Lys Asp Lys Arg Glu Tyr Glu Lys
565 570 575
Asn Asn Glu Lys Arg Ser Ile Phe Arg Ser Ser Leu Ser Glu Gln Leu
580 585 590
Arg Ala Asp Glu Gln Met Glu Lys Val Arg Glu Ser Asp Leu Arg Arg
595 600 605
Leu Glu Ala Ile Gln Arg Gln Asn Gly Gln Cys Leu Tyr Cys Gly Arg
610 615 620
Thr Ile Thr Phe Arg Thr Cys Glu Met Asp His Ile Val Pro Arg Lys
625 630 635 640
Gly Val Gly Ser Thr Asn Thr Arg Thr Asn Phe Ala Ala Val Cys Ala
645 650 655
Glu Cys Asn Arg Met Lys Ser Asn Thr Pro Phe Ala Ile Trp Ala Arg
660 665 670
Ser Glu Asp Ala Gln Thr Arg Gly Val Ser Leu Ala Glu Ala Lys Lys
675 680 685
Arg Val Thr Met Phe Thr Phe Asn Pro Lys Ser Tyr Ala Pro Arg Glu
690 695 700
Val Lys Ala Phe Lys Gln Ala Val Ile Ala Arg Leu Gln Gln Thr Glu
705 710 715 720
Asp Asp Ala Ala Ile Asp Asn Arg Ser Ile Glu Ser Val Ala Trp Met
725 730 735
Ala Asp Glu Leu His Arg Arg Ile Asp Trp Tyr Phe Asn Ala Lys Gln
740 745 750
Tyr Val Asn Ser Ala Ser Ile Asp Asp Ala Glu Ala Glu Thr Met Lys
755 760 765
Thr Thr Val Ser Val Phe Gln Gly Arg Val Thr Ala Ser Ala Arg Arg
770 775 780
Ala Ala Gly Ile Glu Gly Lys Ile His Phe Ile Gly Gln Gln Ser Lys
785 790 795 800
Thr Arg Leu Asp Arg Arg His His Ala Val Asp Ala Ser Val Ile Ala
805 810 815
Met Met Asn Thr Ala Ala Ala Gln Thr Leu Met Glu Arg Glu Ser Leu
820 825 830
Arg Glu Ser Gln Arg Leu Ile Gly Leu Met Pro Gly Glu Arg Ser Trp
835 840 845
Lys Glu Tyr Pro Tyr Glu Gly Thr Ser Arg Tyr Glu Ser Phe His Leu
850 855 860
Trp Leu Asp Asn Met Asp Val Leu Leu Glu Leu Leu Asn Asp Ala Leu
865 870 875 880
Asp Asn Asp Arg Ile Ala Val Met Gln Ser Gln Arg Tyr Val Leu Gly
885 890 895
Asn Ser Ile Ala His Asp Ala Thr Ile His Pro Leu Glu Lys Val Pro
900 905 910
Leu Gly Ser Ala Met Ser Ala Asp Leu Ile Arg Arg Ala Ser Thr Pro
915 920 925
Ala Leu Trp Cys Ala Leu Thr Arg Leu Pro Asp Tyr Asp Glu Lys Glu
930 935 940
Gly Leu Pro Glu Asp Ser His Arg Glu Ile Arg Val His Asp Thr Arg
945 950 955 960
Tyr Ser Ala Asp Asp Glu Met Gly Phe Phe Ala Ser Gln Ala Ala Gln
965 970 975
Ile Ala Val Gln Glu Gly Ser Ala Asp Ile Gly Ser Ala Ile His His
980 985 990
Ala Arg Val Tyr Arg Cys Trp Lys Thr Asn Ala Lys Gly Val Arg Lys
995 1000 1005
Tyr Phe Tyr Gly Met Ile Arg Val Phe Gln Thr Asp Leu Leu Arg
1010 1015 1020
Ala Cys His Asp Asp Leu Phe Thr Val Pro Leu Pro Pro Gln Ser
1025 1030 1035
Ile Ser Met Arg Tyr Gly Glu Pro Arg Val Val Gln Ala Leu Gln
1040 1045 1050
Ser Gly Asn Ala Gln Tyr Leu Gly Ser Leu Val Val Gly Asp Glu
1055 1060 1065
Ile Glu Met Asp Phe Ser Ser Leu Asp Val Asp Gly Gln Ile Gly
1070 1075 1080
Glu Tyr Leu Gln Phe Phe Ser Gln Phe Ser Gly Gly Asn Leu Ala
1085 1090 1095
Trp Lys His Trp Val Val Asp Gly Phe Phe Asn Gln Thr Gln Leu
1100 1105 1110
Arg Ile Arg Pro Arg Tyr Leu Ala Ala Glu Gly Leu Ala Lys Ala
1115 1120 1125
Phe Ser Asp Asp Val Val Pro Asp Gly Val Gln Lys Ile Val Thr
1130 1135 1140
Lys Gln Gly Trp Leu Pro Pro Val Asn Thr Ala Ser Lys Thr Ala
1145 1150 1155
Val Arg Ile Val Arg Arg Asn Ala Phe Gly Glu Pro Arg Leu Ser
1160 1165 1170
Ser Ala His His Met Pro Cys Ser Trp Gln Trp Arg His Glu
1175 1180 1185
<210> 170
<211> 1101
<212> PRT
<213> 嗜粘蛋白艾克曼菌（Akkermansia muciniphila）
<400> 170
Met Ser Arg Ser Leu Thr Phe Ser Phe Asp Ile Gly Tyr Ala Ser Ile
1 5 10 15
Gly Trp Ala Val Ile Ala Ser Ala Ser His Asp Asp Ala Asp Pro Ser
20 25 30
Val Cys Gly Cys Gly Thr Val Leu Phe Pro Lys Asp Asp Cys Gln Ala
35 40 45
Phe Lys Arg Arg Glu Tyr Arg Arg Leu Arg Arg Asn Ile Arg Ser Arg
50 55 60
Arg Val Arg Ile Glu Arg Ile Gly Arg Leu Leu Val Gln Ala Gln Ile
65 70 75 80
Ile Thr Pro Glu Met Lys Glu Thr Ser Gly His Pro Ala Pro Phe Tyr
85 90 95
Leu Ala Ser Glu Ala Leu Lys Gly His Arg Thr Leu Ala Pro Ile Glu
100 105 110
Leu Trp His Val Leu Arg Trp Tyr Ala His Asn Arg Gly Tyr Asp Asn
115 120 125
Asn Ala Ser Trp Ser Asn Ser Leu Ser Glu Asp Gly Gly Asn Gly Glu
130 135 140
Asp Thr Glu Arg Val Lys His Ala Gln Asp Leu Met Asp Lys His Gly
145 150 155 160
Thr Ala Thr Met Ala Glu Thr Ile Cys Arg Glu Leu Lys Leu Glu Glu
165 170 175
Gly Lys Ala Asp Ala Pro Met Glu Val Ser Thr Pro Ala Tyr Lys Asn
180 185 190
Leu Asn Thr Ala Phe Pro Arg Leu Ile Val Glu Lys Glu Val Arg Arg
195 200 205
Ile Leu Glu Leu Ser Ala Pro Leu Ile Pro Gly Leu Thr Ala Glu Ile
210 215 220
Ile Glu Leu Ile Ala Gln His His Pro Leu Thr Thr Glu Gln Arg Gly
225 230 235 240
Val Leu Leu Gln His Gly Ile Lys Leu Ala Arg Arg Tyr Arg Gly Ser
245 250 255
Leu Leu Phe Gly Gln Leu Ile Pro Arg Phe Asp Asn Arg Ile Ile Ser
260 265 270
Arg Cys Pro Val Thr Trp Ala Gln Val Tyr Glu Ala Glu Leu Lys Lys
275 280 285
Gly Asn Ser Glu Gln Ser Ala Arg Glu Arg Ala Glu Lys Leu Ser Lys
290 295 300
Val Pro Thr Ala Asn Cys Pro Glu Phe Tyr Glu Tyr Arg Met Ala Arg
305 310 315 320
Ile Leu Cys Asn Ile Arg Ala Asp Gly Glu Pro Leu Ser Ala Glu Ile
325 330 335
Arg Arg Glu Leu Met Asn Gln Ala Arg Gln Glu Gly Lys Leu Thr Lys
340 345 350
Ala Ser Leu Glu Lys Ala Ile Ser Ser Arg Leu Gly Lys Glu Thr Glu
355 360 365
Thr Asn Val Ser Asn Tyr Phe Thr Leu His Pro Asp Ser Glu Glu Ala
370 375 380
Leu Tyr Leu Asn Pro Ala Val Glu Val Leu Gln Arg Ser Gly Ile Gly
385 390 395 400
Gln Ile Leu Ser Pro Ser Val Tyr Arg Ile Ala Ala Asn Arg Leu Arg
405 410 415
Arg Gly Lys Ser Val Thr Pro Asn Tyr Leu Leu Asn Leu Leu Lys Ser
420 425 430
Arg Gly Glu Ser Gly Glu Ala Leu Glu Lys Lys Ile Glu Lys Glu Ser
435 440 445
Lys Lys Lys Glu Ala Asp Tyr Ala Asp Thr Pro Leu Lys Pro Lys Tyr
450 455 460
Ala Thr Gly Arg Ala Pro Tyr Ala Arg Thr Val Leu Lys Lys Val Val
465 470 475 480
Glu Glu Ile Leu Asp Gly Glu Asp Pro Thr Arg Pro Ala Arg Gly Glu
485 490 495
Ala His Pro Asp Gly Glu Leu Lys Ala His Asp Gly Cys Leu Tyr Cys
500 505 510
Leu Leu Asp Thr Asp Ser Ser Val Asn Gln His Gln Lys Glu Arg Arg
515 520 525
Leu Asp Thr Met Thr Asn Asn His Leu Val Arg His Arg Met Leu Ile
530 535 540
Leu Asp Arg Leu Leu Lys Asp Leu Ile Gln Asp Phe Ala Asp Gly Gln
545 550 555 560
Lys Asp Arg Ile Ser Arg Val Cys Val Glu Val Gly Lys Glu Leu Thr
565 570 575
Thr Phe Ser Ala Met Asp Ser Lys Lys Ile Gln Arg Glu Leu Thr Leu
580 585 590
Arg Gln Lys Ser His Thr Asp Ala Val Asn Arg Leu Lys Arg Lys Leu
595 600 605
Pro Gly Lys Ala Leu Ser Ala Asn Leu Ile Arg Lys Cys Arg Ile Ala
610 615 620
Met Asp Met Asn Trp Thr Cys Pro Phe Thr Gly Ala Thr Tyr Gly Asp
625 630 635 640
His Glu Leu Glu Asn Leu Glu Leu Glu His Ile Val Pro His Ser Phe
645 650 655
Arg Gln Ser Asn Ala Leu Ser Ser Leu Val Leu Thr Trp Pro Gly Val
660 665 670
Asn Arg Met Lys Gly Gln Arg Thr Gly Tyr Asp Phe Val Glu Gln Glu
675 680 685
Gln Glu Asn Pro Val Pro Asp Lys Pro Asn Leu His Ile Cys Ser Leu
690 695 700
Asn Asn Tyr Arg Glu Leu Val Glu Lys Leu Asp Asp Lys Lys Gly His
705 710 715 720
Glu Asp Asp Arg Arg Arg Lys Lys Lys Arg Lys Ala Leu Leu Met Val
725 730 735
Arg Gly Leu Ser His Lys His Gln Ser Gln Asn His Glu Ala Met Lys
740 745 750
Glu Ile Gly Met Thr Glu Gly Met Met Thr Gln Ser Ser His Leu Met
755 760 765
Lys Leu Ala Cys Lys Ser Ile Lys Thr Ser Leu Pro Asp Ala His Ile
770 775 780
Asp Met Ile Pro Gly Ala Val Thr Ala Glu Val Arg Lys Ala Trp Asp
785 790 795 800
Val Phe Gly Val Phe Lys Glu Leu Cys Pro Glu Ala Ala Asp Pro Asp
805 810 815
Ser Gly Lys Ile Leu Lys Glu Asn Leu Arg Ser Leu Thr His Leu His
820 825 830
His Ala Leu Asp Ala Cys Val Leu Gly Leu Ile Pro Tyr Ile Ile Pro
835 840 845
Ala His His Asn Gly Leu Leu Arg Arg Val Leu Ala Met Arg Arg Ile
850 855 860
Pro Glu Lys Leu Ile Pro Gln Val Arg Pro Val Ala Asn Gln Arg His
865 870 875 880
Tyr Val Leu Asn Asp Asp Gly Arg Met Met Leu Arg Asp Leu Ser Ala
885 890 895
Ser Leu Lys Glu Asn Ile Arg Glu Gln Leu Met Glu Gln Arg Val Ile
900 905 910
Gln His Val Pro Ala Asp Met Gly Gly Ala Leu Leu Lys Glu Thr Met
915 920 925
Gln Arg Val Leu Ser Val Asp Gly Ser Gly Glu Asp Ala Met Val Ser
930 935 940
Leu Ser Lys Lys Lys Asp Gly Lys Lys Glu Lys Asn Gln Val Lys Ala
945 950 955 960
Ser Lys Leu Val Gly Val Phe Pro Glu Gly Pro Ser Lys Leu Lys Ala
965 970 975
Leu Lys Ala Ala Ile Glu Ile Asp Gly Asn Tyr Gly Val Ala Leu Asp
980 985 990
Pro Lys Pro Val Val Ile Arg His Ile Lys Val Phe Lys Arg Ile Met
995 1000 1005
Ala Leu Lys Glu Gln Asn Gly Gly Lys Pro Val Arg Ile Leu Lys
1010 1015 1020
Lys Gly Met Leu Ile His Leu Thr Ser Ser Lys Asp Pro Lys His
1025 1030 1035
Ala Gly Val Trp Arg Ile Glu Ser Ile Gln Asp Ser Lys Gly Gly
1040 1045 1050
Val Lys Leu Asp Leu Gln Arg Ala His Cys Ala Val Pro Lys Asn
1055 1060 1065
Lys Thr His Glu Cys Asn Trp Arg Glu Val Asp Leu Ile Ser Leu
1070 1075 1080
Leu Lys Lys Tyr Gln Met Lys Arg Tyr Pro Thr Ser Tyr Thr Gly
1085 1090 1095
Thr Pro Arg
1100
<210> 171
<211> 1498
<212> PRT
<213> 兰氏臭杆菌（Odoribacter laneus）
<400> 171
Met Glu Thr Thr Leu Gly Ile Asp Leu Gly Thr Asn Ser Ile Gly Leu
1 5 10 15
Ala Leu Val Asp Gln Glu Glu His Gln Ile Leu Tyr Ser Gly Val Arg
20 25 30
Ile Phe Pro Glu Gly Ile Asn Lys Asp Thr Ile Gly Leu Gly Glu Lys
35 40 45
Glu Glu Ser Arg Asn Ala Thr Arg Arg Ala Lys Arg Gln Met Arg Arg
50 55 60
Gln Tyr Phe Arg Lys Lys Leu Arg Lys Ala Lys Leu Leu Glu Leu Leu
65 70 75 80
Ile Ala Tyr Asp Met Cys Pro Leu Lys Pro Glu Asp Val Arg Arg Trp
85 90 95
Lys Asn Trp Asp Lys Gln Gln Lys Ser Thr Val Arg Gln Phe Pro Asp
100 105 110
Thr Pro Ala Phe Arg Glu Trp Leu Lys Gln Asn Pro Tyr Glu Leu Arg
115 120 125
Lys Gln Ala Val Thr Glu Asp Val Thr Arg Pro Glu Leu Gly Arg Ile
130 135 140
Leu Tyr Gln Met Ile Gln Arg Arg Gly Phe Leu Ser Ser Arg Lys Gly
145 150 155 160
Lys Glu Glu Gly Lys Ile Phe Thr Gly Lys Asp Arg Met Val Gly Ile
165 170 175
Asp Glu Thr Arg Lys Asn Leu Gln Lys Gln Thr Leu Gly Ala Tyr Leu
180 185 190
Tyr Asp Ile Ala Pro Lys Asn Gly Glu Lys Tyr Arg Phe Arg Thr Glu
195 200 205
Arg Val Arg Ala Arg Tyr Thr Leu Arg Asp Met Tyr Ile Arg Glu Phe
210 215 220
Glu Ile Ile Trp Gln Arg Gln Ala Gly His Leu Gly Leu Ala His Glu
225 230 235 240
Gln Ala Thr Arg Lys Lys Asn Ile Phe Leu Glu Gly Ser Ala Thr Asn
245 250 255
Val Arg Asn Ser Lys Leu Ile Thr His Leu Gln Ala Lys Tyr Gly Arg
260 265 270
Gly His Val Leu Ile Glu Asp Thr Arg Ile Thr Val Thr Phe Gln Leu
275 280 285
Pro Leu Lys Glu Val Leu Gly Gly Lys Ile Glu Ile Glu Glu Glu Gln
290 295 300
Leu Lys Phe Lys Ser Asn Glu Ser Val Leu Phe Trp Gln Arg Pro Leu
305 310 315 320
Arg Ser Gln Lys Ser Leu Leu Ser Lys Cys Val Phe Glu Gly Arg Asn
325 330 335
Phe Tyr Asp Pro Val His Gln Lys Trp Ile Ile Ala Gly Pro Thr Pro
340 345 350
Ala Pro Leu Ser His Pro Glu Phe Glu Glu Phe Arg Ala Tyr Gln Phe
355 360 365
Ile Asn Asn Ile Ile Tyr Gly Lys Asn Glu His Leu Thr Ala Ile Gln
370 375 380
Arg Glu Ala Val Phe Glu Leu Met Cys Thr Glu Ser Lys Asp Phe Asn
385 390 395 400
Phe Glu Lys Ile Pro Lys His Leu Lys Leu Phe Glu Lys Phe Asn Phe
405 410 415
Asp Asp Thr Thr Lys Val Pro Ala Cys Thr Thr Ile Ser Gln Leu Arg
420 425 430
Lys Leu Phe Pro His Pro Val Trp Glu Glu Lys Arg Glu Glu Ile Trp
435 440 445
His Cys Phe Tyr Phe Tyr Asp Asp Asn Thr Leu Leu Phe Glu Lys Leu
450 455 460
Gln Lys Asp Tyr Ala Leu Gln Thr Asn Asp Leu Glu Lys Ile Lys Lys
465 470 475 480
Ile Arg Leu Ser Glu Ser Tyr Gly Asn Val Ser Leu Lys Ala Ile Arg
485 490 495
Arg Ile Asn Pro Tyr Leu Lys Lys Gly Tyr Ala Tyr Ser Thr Ala Val
500 505 510
Leu Leu Gly Gly Ile Arg Asn Ser Phe Gly Lys Arg Phe Glu Tyr Phe
515 520 525
Lys Glu Tyr Glu Pro Glu Ile Glu Lys Ala Val Cys Arg Ile Leu Lys
530 535 540
Glu Lys Asn Ala Glu Gly Glu Val Ile Arg Lys Ile Lys Asp Tyr Leu
545 550 555 560
Val His Asn Arg Phe Gly Phe Ala Lys Asn Asp Arg Ala Phe Gln Lys
565 570 575
Leu Tyr His His Ser Gln Ala Ile Thr Thr Gln Ala Gln Lys Glu Arg
580 585 590
Leu Pro Glu Thr Gly Asn Leu Arg Asn Pro Ile Val Gln Gln Gly Leu
595 600 605
Asn Glu Leu Arg Arg Thr Val Asn Lys Leu Leu Ala Thr Cys Arg Glu
610 615 620
Lys Tyr Gly Pro Ser Phe Lys Phe Asp His Ile His Val Glu Met Gly
625 630 635 640
Arg Glu Leu Arg Ser Ser Lys Thr Glu Arg Glu Lys Gln Ser Arg Gln
645 650 655
Ile Arg Glu Asn Glu Lys Lys Asn Glu Ala Ala Lys Val Lys Leu Ala
660 665 670
Glu Tyr Gly Leu Lys Ala Tyr Arg Asp Asn Ile Gln Lys Tyr Leu Leu
675 680 685
Tyr Lys Glu Ile Glu Glu Lys Gly Gly Thr Val Cys Cys Pro Tyr Thr
690 695 700
Gly Lys Thr Leu Asn Ile Ser His Thr Leu Gly Ser Asp Asn Ser Val
705 710 715 720
Gln Ile Glu His Ile Ile Pro Tyr Ser Ile Ser Leu Asp Asp Ser Leu
725 730 735
Ala Asn Lys Thr Leu Cys Asp Ala Thr Phe Asn Arg Glu Lys Gly Glu
740 745 750
Leu Thr Pro Tyr Asp Phe Tyr Gln Lys Asp Pro Ser Pro Glu Lys Trp
755 760 765
Gly Ala Ser Ser Trp Glu Glu Ile Glu Asp Arg Ala Phe Arg Leu Leu
770 775 780
Pro Tyr Ala Lys Ala Gln Arg Phe Ile Arg Arg Lys Pro Gln Glu Ser
785 790 795 800
Asn Glu Phe Ile Ser Arg Gln Leu Asn Asp Thr Arg Tyr Ile Ser Lys
805 810 815
Lys Ala Val Glu Tyr Leu Ser Ala Ile Cys Ser Asp Val Lys Ala Phe
820 825 830
Pro Gly Gln Leu Thr Ala Glu Leu Arg His Leu Trp Gly Leu Asn Asn
835 840 845
Ile Leu Gln Ser Ala Pro Asp Ile Thr Phe Pro Leu Pro Val Ser Ala
850 855 860
Thr Glu Asn His Arg Glu Tyr Tyr Val Ile Thr Asn Glu Gln Asn Glu
865 870 875 880
Val Ile Arg Leu Phe Pro Lys Gln Gly Glu Thr Pro Arg Thr Glu Lys
885 890 895
Gly Glu Leu Leu Leu Thr Gly Glu Val Glu Arg Lys Val Phe Arg Cys
900 905 910
Lys Gly Met Gln Glu Phe Gln Thr Asp Val Ser Asp Gly Lys Tyr Trp
915 920 925
Arg Arg Ile Lys Leu Ser Ser Ser Val Thr Trp Ser Pro Leu Phe Ala
930 935 940
Pro Lys Pro Ile Ser Ala Asp Gly Gln Ile Val Leu Lys Gly Arg Ile
945 950 955 960
Glu Lys Gly Val Phe Val Cys Asn Gln Leu Lys Gln Lys Leu Lys Thr
965 970 975
Gly Leu Pro Asp Gly Ser Tyr Trp Ile Ser Leu Pro Val Ile Ser Gln
980 985 990
Thr Phe Lys Glu Gly Glu Ser Val Asn Asn Ser Lys Leu Thr Ser Gln
995 1000 1005
Gln Val Gln Leu Phe Gly Arg Val Arg Glu Gly Ile Phe Arg Cys
1010 1015 1020
His Asn Tyr Gln Cys Pro Ala Ser Gly Ala Asp Gly Asn Phe Trp
1025 1030 1035
Cys Thr Leu Asp Thr Asp Thr Ala Gln Pro Ala Phe Thr Pro Ile
1040 1045 1050
Lys Asn Ala Pro Pro Gly Val Gly Gly Gly Gln Ile Ile Leu Thr
1055 1060 1065
Gly Asp Val Asp Asp Lys Gly Ile Phe His Ala Asp Asp Asp Leu
1070 1075 1080
His Tyr Glu Leu Pro Ala Ser Leu Pro Lys Gly Lys Tyr Tyr Gly
1085 1090 1095
Ile Phe Thr Val Glu Ser Cys Asp Pro Thr Leu Ile Pro Ile Glu
1100 1105 1110
Leu Ser Ala Pro Lys Thr Ser Lys Gly Glu Asn Leu Ile Glu Gly
1115 1120 1125
Asn Ile Trp Val Asp Glu His Thr Gly Glu Val Arg Phe Asp Pro
1130 1135 1140
Lys Lys Asn Arg Glu Asp Gln Arg His His Ala Ile Asp Ala Ile
1145 1150 1155
Val Ile Ala Leu Ser Ser Gln Ser Leu Phe Gln Arg Leu Ser Thr
1160 1165 1170
Tyr Asn Ala Arg Arg Glu Asn Lys Lys Arg Gly Leu Asp Ser Thr
1175 1180 1185
Glu His Phe Pro Ser Pro Trp Pro Gly Phe Ala Gln Asp Val Arg
1190 1195 1200
Gln Ser Val Val Pro Leu Leu Val Ser Tyr Lys Gln Asn Pro Lys
1205 1210 1215
Thr Leu Cys Lys Ile Ser Lys Thr Leu Tyr Lys Asp Gly Lys Lys
1220 1225 1230
Ile His Ser Cys Gly Asn Ala Val Arg Gly Gln Leu His Lys Glu
1235 1240 1245
Thr Val Tyr Gly Gln Arg Thr Ala Pro Gly Ala Thr Glu Lys Ser
1250 1255 1260
Tyr His Ile Arg Lys Asp Ile Arg Glu Leu Lys Thr Ser Lys His
1265 1270 1275
Ile Gly Lys Val Val Asp Ile Thr Ile Arg Gln Met Leu Leu Lys
1280 1285 1290
His Leu Gln Glu Asn Tyr His Ile Asp Ile Thr Gln Glu Phe Asn
1295 1300 1305
Ile Pro Ser Asn Ala Phe Phe Lys Glu Gly Val Tyr Arg Ile Phe
1310 1315 1320
Leu Pro Asn Lys His Gly Glu Pro Val Pro Ile Lys Lys Ile Arg
1325 1330 1335
Met Lys Glu Glu Leu Gly Asn Ala Glu Arg Leu Lys Asp Asn Ile
1340 1345 1350
Asn Gln Tyr Val Asn Pro Arg Asn Asn His His Val Met Ile Tyr
1355 1360 1365
Gln Asp Ala Asp Gly Asn Leu Lys Glu Glu Ile Val Ser Phe Trp
1370 1375 1380
Ser Val Ile Glu Arg Gln Asn Gln Gly Gln Pro Ile Tyr Gln Leu
1385 1390 1395
Pro Arg Glu Gly Arg Asn Ile Val Ser Ile Leu Gln Ile Asn Asp
1400 1405 1410
Thr Phe Leu Ile Gly Leu Lys Glu Glu Glu Pro Glu Val Tyr Arg
1415 1420 1425
Asn Asp Leu Ser Thr Leu Ser Lys His Leu Tyr Arg Val Gln Lys
1430 1435 1440
Leu Ser Gly Met Tyr Tyr Thr Phe Arg His His Leu Ala Ser Thr
1445 1450 1455
Leu Asn Asn Glu Arg Glu Glu Phe Arg Ile Gln Ser Leu Glu Ala
1460 1465 1470
Trp Lys Arg Ala Asn Pro Val Lys Val Gln Ile Asp Glu Ile Gly
1475 1480 1485
Arg Ile Thr Phe Leu Asn Gly Pro Leu Cys
1490 1495
<210> 172
<211> 1300
<212> PRT
<213> 土拉热弗朗西丝菌新凶手亚种（Francisella tularensis subsp. Novicida）
<400> 172
Met Ser Ile Tyr Gln Glu Phe Val Asn Lys Tyr Ser Leu Ser Lys Thr
1 5 10 15
Leu Arg Phe Glu Leu Ile Pro Gln Gly Lys Thr Leu Glu Asn Ile Lys
20 25 30
Ala Arg Gly Leu Ile Leu Asp Asp Glu Lys Arg Ala Lys Asp Tyr Lys
35 40 45
Lys Ala Lys Gln Ile Ile Asp Lys Tyr His Gln Phe Phe Ile Glu Glu
50 55 60
Ile Leu Ser Ser Val Cys Ile Ser Glu Asp Leu Leu Gln Asn Tyr Ser
65 70 75 80
Asp Val Tyr Phe Lys Leu Lys Lys Ser Asp Asp Asp Asn Leu Gln Lys
85 90 95
Asp Phe Lys Ser Ala Lys Asp Thr Ile Lys Lys Gln Ile Ser Glu Tyr
100 105 110
Ile Lys Asp Ser Glu Lys Phe Lys Asn Leu Phe Asn Gln Asn Leu Ile
115 120 125
Asp Ala Lys Lys Gly Gln Glu Ser Asp Leu Ile Leu Trp Leu Lys Gln
130 135 140
Ser Lys Asp Asn Gly Ile Glu Leu Phe Lys Ala Asn Ser Asp Ile Thr
145 150 155 160
Asp Ile Asp Glu Ala Leu Glu Ile Ile Lys Ser Phe Lys Gly Trp Thr
165 170 175
Thr Tyr Phe Lys Gly Phe His Glu Asn Arg Lys Asn Val Tyr Ser Ser
180 185 190
Asn Asp Ile Pro Thr Ser Ile Ile Tyr Arg Ile Val Asp Asp Asn Leu
195 200 205
Pro Lys Phe Leu Glu Asn Lys Ala Lys Tyr Glu Ser Leu Lys Asp Lys
210 215 220
Ala Pro Glu Ala Ile Asn Tyr Glu Gln Ile Lys Lys Asp Leu Ala Glu
225 230 235 240
Glu Leu Thr Phe Asp Ile Asp Tyr Lys Thr Ser Glu Val Asn Gln Arg
245 250 255
Val Phe Ser Leu Asp Glu Val Phe Glu Ile Ala Asn Phe Asn Asn Tyr
260 265 270
Leu Asn Gln Ser Gly Ile Thr Lys Phe Asn Thr Ile Ile Gly Gly Lys
275 280 285
Phe Val Asn Gly Glu Asn Thr Lys Arg Lys Gly Ile Asn Glu Tyr Ile
290 295 300
Asn Leu Tyr Ser Gln Gln Ile Asn Asp Lys Thr Leu Lys Lys Tyr Lys
305 310 315 320
Met Ser Val Leu Phe Lys Gln Ile Leu Ser Asp Thr Glu Ser Lys Ser
325 330 335
Phe Val Ile Asp Lys Leu Glu Asp Asp Ser Asp Val Val Thr Thr Met
340 345 350
Gln Ser Phe Tyr Glu Gln Ile Ala Ala Phe Lys Thr Val Glu Glu Lys
355 360 365
Ser Ile Lys Glu Thr Leu Ser Leu Leu Phe Asp Asp Leu Lys Ala Gln
370 375 380
Lys Leu Asp Leu Ser Lys Ile Tyr Phe Lys Asn Asp Lys Ser Leu Thr
385 390 395 400
Asp Leu Ser Gln Gln Val Phe Asp Asp Tyr Ser Val Ile Gly Thr Ala
405 410 415
Val Leu Glu Tyr Ile Thr Gln Gln Ile Ala Pro Lys Asn Leu Asp Asn
420 425 430
Pro Ser Lys Lys Glu Gln Glu Leu Ile Ala Lys Lys Thr Glu Lys Ala
435 440 445
Lys Tyr Leu Ser Leu Glu Thr Ile Lys Leu Ala Leu Glu Glu Phe Asn
450 455 460
Lys His Arg Asp Ile Asp Lys Gln Cys Arg Phe Glu Glu Ile Leu Ala
465 470 475 480
Asn Phe Ala Ala Ile Pro Met Ile Phe Asp Glu Ile Ala Gln Asn Lys
485 490 495
Asp Asn Leu Ala Gln Ile Ser Ile Lys Tyr Gln Asn Gln Gly Lys Lys
500 505 510
Asp Leu Leu Gln Ala Ser Ala Glu Asp Asp Val Lys Ala Ile Lys Asp
515 520 525
Leu Leu Asp Gln Thr Asn Asn Leu Leu His Lys Leu Lys Ile Phe His
530 535 540
Ile Ser Gln Ser Glu Asp Lys Ala Asn Ile Leu Asp Lys Asp Glu His
545 550 555 560
Phe Tyr Leu Val Phe Glu Glu Cys Tyr Phe Glu Leu Ala Asn Ile Val
565 570 575
Pro Leu Tyr Asn Lys Ile Arg Asn Tyr Ile Thr Gln Lys Pro Tyr Ser
580 585 590
Asp Glu Lys Phe Lys Leu Asn Phe Glu Asn Ser Thr Leu Ala Asn Gly
595 600 605
Trp Asp Lys Asn Lys Glu Pro Asp Asn Thr Ala Ile Leu Phe Ile Lys
610 615 620
Asp Asp Lys Tyr Tyr Leu Gly Val Met Asn Lys Lys Asn Asn Lys Ile
625 630 635 640
Phe Asp Asp Lys Ala Ile Lys Glu Asn Lys Gly Glu Gly Tyr Lys Lys
645 650 655
Ile Val Tyr Lys Leu Leu Pro Gly Ala Asn Lys Met Leu Pro Lys Val
660 665 670
Phe Phe Ser Ala Lys Ser Ile Lys Phe Tyr Asn Pro Ser Glu Asp Ile
675 680 685
Leu Arg Ile Arg Asn His Ser Thr His Thr Lys Asn Gly Ser Pro Gln
690 695 700
Lys Gly Tyr Glu Lys Phe Glu Phe Asn Ile Glu Asp Cys Arg Lys Phe
705 710 715 720
Ile Asp Phe Tyr Lys Gln Ser Ile Ser Lys His Pro Glu Trp Lys Asp
725 730 735
Phe Gly Phe Arg Phe Ser Asp Thr Gln Arg Tyr Asn Ser Ile Asp Glu
740 745 750
Phe Tyr Arg Glu Val Glu Asn Gln Gly Tyr Lys Leu Thr Phe Glu Asn
755 760 765
Ile Ser Glu Ser Tyr Ile Asp Ser Val Val Asn Gln Gly Lys Leu Tyr
770 775 780
Leu Phe Gln Ile Tyr Asn Lys Asp Phe Ser Ala Tyr Ser Lys Gly Arg
785 790 795 800
Pro Asn Leu His Thr Leu Tyr Trp Lys Ala Leu Phe Asp Glu Arg Asn
805 810 815
Leu Gln Asp Val Val Tyr Lys Leu Asn Gly Glu Ala Glu Leu Phe Tyr
820 825 830
Arg Lys Gln Ser Ile Pro Lys Lys Ile Thr His Pro Ala Lys Glu Ala
835 840 845
Ile Ala Asn Lys Asn Lys Asp Asn Pro Lys Lys Glu Ser Val Phe Glu
850 855 860
Tyr Asp Leu Ile Lys Asp Lys Arg Phe Thr Glu Asp Lys Phe Phe Phe
865 870 875 880
His Cys Pro Ile Thr Ile Asn Phe Lys Ser Ser Gly Ala Asn Lys Phe
885 890 895
Asn Asp Glu Ile Asn Leu Leu Leu Lys Glu Lys Ala Asn Asp Val His
900 905 910
Ile Leu Ser Ile Asp Arg Gly Glu Arg His Leu Ala Tyr Tyr Thr Leu
915 920 925
Val Asp Gly Lys Gly Asn Ile Ile Lys Gln Asp Thr Phe Asn Ile Ile
930 935 940
Gly Asn Asp Arg Met Lys Thr Asn Tyr His Asp Lys Leu Ala Ala Ile
945 950 955 960
Glu Lys Asp Arg Asp Ser Ala Arg Lys Asp Trp Lys Lys Ile Asn Asn
965 970 975
Ile Lys Glu Met Lys Glu Gly Tyr Leu Ser Gln Val Val His Glu Ile
980 985 990
Ala Lys Leu Val Ile Glu Tyr Asn Ala Ile Val Val Phe Glu Asp Leu
995 1000 1005
Asn Phe Gly Phe Lys Arg Gly Arg Phe Lys Val Glu Lys Gln Val
1010 1015 1020
Tyr Gln Lys Leu Glu Lys Met Leu Ile Glu Lys Leu Asn Tyr Leu
1025 1030 1035
Val Phe Lys Asp Asn Glu Phe Asp Lys Thr Gly Gly Val Leu Arg
1040 1045 1050
Ala Tyr Gln Leu Thr Ala Pro Phe Glu Thr Phe Lys Lys Met Gly
1055 1060 1065
Lys Gln Thr Gly Ile Ile Tyr Tyr Val Pro Ala Gly Phe Thr Ser
1070 1075 1080
Lys Ile Cys Pro Val Thr Gly Phe Val Asn Gln Leu Tyr Pro Lys
1085 1090 1095
Tyr Glu Ser Val Ser Lys Ser Gln Glu Phe Phe Ser Lys Phe Asp
1100 1105 1110
Lys Ile Cys Tyr Asn Leu Asp Lys Gly Tyr Phe Glu Phe Ser Phe
1115 1120 1125
Asp Tyr Lys Asn Phe Gly Asp Lys Ala Ala Lys Gly Lys Trp Thr
1130 1135 1140
Ile Ala Ser Phe Gly Ser Arg Leu Ile Asn Phe Arg Asn Ser Asp
1145 1150 1155
Lys Asn His Asn Trp Asp Thr Arg Glu Val Tyr Pro Thr Lys Glu
1160 1165 1170
Leu Glu Lys Leu Leu Lys Asp Tyr Ser Ile Glu Tyr Gly His Gly
1175 1180 1185
Glu Cys Ile Lys Ala Ala Ile Cys Gly Glu Ser Asp Lys Lys Phe
1190 1195 1200
Phe Ala Lys Leu Thr Ser Val Leu Asn Thr Ile Leu Gln Met Arg
1205 1210 1215
Asn Ser Lys Thr Gly Thr Glu Leu Asp Tyr Leu Ile Ser Pro Val
1220 1225 1230
Ala Asp Val Asn Gly Asn Phe Phe Asp Ser Arg Gln Ala Pro Lys
1235 1240 1245
Asn Met Pro Gln Asp Ala Asp Ala Asn Gly Ala Tyr His Ile Gly
1250 1255 1260
Leu Lys Gly Leu Met Leu Leu Gly Arg Ile Lys Asn Asn Gln Glu
1265 1270 1275
Gly Lys Lys Leu Asn Leu Val Ile Lys Asn Glu Glu Tyr Phe Glu
1280 1285 1290
Phe Val Gln Asn Arg Asn Asn
1295 1300
<210> 173
<211> 1228
<212> PRT
<213> 毛螺科细菌物种（Lachnospiraceae bacterium sp.）ND2006
<400> 173
Ala Ala Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys
1 5 10 15
Thr Leu Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile
20 25 30
Asp Asn Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr
35 40 45
Lys Gly Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn
50 55 60
Asp Val Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser
65 70 75 80
Leu Phe Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu
85 90 95
Asn Leu Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly
100 105 110
Ala Ala Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile
115 120 125
Leu Pro Glu Ala Ala Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser
130 135 140
Phe Asn Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu
145 150 155 160
Asn Met Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys
165 170 175
Ile Asn Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu
180 185 190
Lys Val Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu
195 200 205
Lys Ile Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu
210 215 220
Phe Phe Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala
225 230 235 240
Ile Ile Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu
245 250 255
Asn Glu Tyr Ile Asn Leu Tyr Asn Ala Lys Thr Lys Gln Ala Leu Pro
260 265 270
Lys Phe Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu
275 280 285
Ser Phe Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val
290 295 300
Phe Arg Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys
305 310 315 320
Lys Leu Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly
325 330 335
Ile Phe Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile
340 345 350
Phe Gly Glu Trp Asn Leu Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp
355 360 365
Asp Ile His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp
370 375 380
Asp Arg Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln
385 390 395 400
Leu Gln Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys
405 410 415
Glu Ile Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser
420 425 430
Ser Glu Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys
435 440 445
Lys Asn Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val
450 455 460
Lys Ser Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu
465 470 475 480
Thr Asn Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp
485 490 495
Ile Leu Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val
500 505 510
Thr Gln Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn
515 520 525
Pro Gln Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg
530 535 540
Ala Thr Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp
545 550 555 560
Lys Lys Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn
565 570 575
Gly Asn Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys
580 585 590
Met Leu Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn
595 600 605
Pro Ser Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys
610 615 620
Gly Asp Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe
625 630 635 640
Lys Asp Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe
645 650 655
Asn Phe Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg
660 665 670
Glu Val Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys
675 680 685
Lys Glu Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln
690 695 700
Ile Tyr Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu
705 710 715 720
His Thr Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln
725 730 735
Ile Arg Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu
740 745 750
Lys Lys Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn
755 760 765
Lys Asn Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val
770 775 780
Tyr Lys Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro
785 790 795 800
Ile Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu
805 810 815
Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile
820 825 830
Asp Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys
835 840 845
Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe
850 855 860
Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys
865 870 875 880
Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn
885 890 895
Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile
900 905 910
Cys Glu Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Glu Asp Leu
915 920 925
Asn Ser Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr
930 935 940
Gln Lys Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp
945 950 955 960
Lys Lys Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln
965 970 975
Ile Thr Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly
980 985 990
Phe Ile Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser
995 1000 1005
Thr Gly Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala
1010 1015 1020
Asp Ser Lys Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val
1025 1030 1035
Pro Glu Glu Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe
1040 1045 1050
Ser Arg Thr Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser
1055 1060 1065
Tyr Gly Asn Arg Ile Arg Ile Phe Ala Ala Ala Lys Lys Asn Asn
1070 1075 1080
Val Phe Ala Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu
1085 1090 1095
Leu Phe Asn Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg
1100 1105 1110
Ala Leu Leu Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe
1115 1120 1125
Met Ala Leu Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr
1130 1135 1140
Gly Arg Thr Asp Val Asp Phe Leu Ile Ser Pro Val Lys Asn Ser
1145 1150 1155
Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn
1160 1165 1170
Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile
1175 1180 1185
Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu
1190 1195 1200
Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1205 1210 1215
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys
1220 1225
<210> 174
<211> 1307
<212> PRT
<213> 氨基酸球菌属物种（Acidaminococcus sp.）BV3L6
<400> 174
Met Thr Gln Phe Glu Gly Phe Thr Asn Leu Tyr Gln Val Ser Lys Thr
1 5 10 15
Leu Arg Phe Glu Leu Ile Pro Gln Gly Lys Thr Leu Lys His Ile Gln
20 25 30
Glu Gln Gly Phe Ile Glu Glu Asp Lys Ala Arg Asn Asp His Tyr Lys
35 40 45
Glu Leu Lys Pro Ile Ile Asp Arg Ile Tyr Lys Thr Tyr Ala Asp Gln
50 55 60
Cys Leu Gln Leu Val Gln Leu Asp Trp Glu Asn Leu Ser Ala Ala Ile
65 70 75 80
Asp Ser Tyr Arg Lys Glu Lys Thr Glu Glu Thr Arg Asn Ala Leu Ile
85 90 95
Glu Glu Gln Ala Thr Tyr Arg Asn Ala Ile His Asp Tyr Phe Ile Gly
100 105 110
Arg Thr Asp Asn Leu Thr Asp Ala Ile Asn Lys Arg His Ala Glu Ile
115 120 125
Tyr Lys Gly Leu Phe Lys Ala Glu Leu Phe Asn Gly Lys Val Leu Lys
130 135 140
Gln Leu Gly Thr Val Thr Thr Thr Glu His Glu Asn Ala Leu Leu Arg
145 150 155 160
Ser Phe Asp Lys Phe Thr Thr Tyr Phe Ser Gly Phe Tyr Glu Asn Arg
165 170 175
Lys Asn Val Phe Ser Ala Glu Asp Ile Ser Thr Ala Ile Pro His Arg
180 185 190
Ile Val Gln Asp Asn Phe Pro Lys Phe Lys Glu Asn Cys His Ile Phe
195 200 205
Thr Arg Leu Ile Thr Ala Val Pro Ser Leu Arg Glu His Phe Glu Asn
210 215 220
Val Lys Lys Ala Ile Gly Ile Phe Val Ser Thr Ser Ile Glu Glu Val
225 230 235 240
Phe Ser Phe Pro Phe Tyr Asn Gln Leu Leu Thr Gln Thr Gln Ile Asp
245 250 255
Leu Tyr Asn Gln Leu Leu Gly Gly Ile Ser Arg Glu Ala Gly Thr Glu
260 265 270
Lys Ile Lys Gly Leu Asn Glu Val Leu Asn Leu Ala Ile Gln Lys Asn
275 280 285
Asp Glu Thr Ala His Ile Ile Ala Ser Leu Pro His Arg Phe Ile Pro
290 295 300
Leu Phe Lys Gln Ile Leu Ser Asp Arg Asn Thr Leu Ser Phe Ile Leu
305 310 315 320
Glu Glu Phe Lys Ser Asp Glu Glu Val Ile Gln Ser Phe Cys Lys Tyr
325 330 335
Lys Thr Leu Leu Arg Asn Glu Asn Val Leu Glu Thr Ala Glu Ala Leu
340 345 350
Phe Asn Glu Leu Asn Ser Ile Asp Leu Thr His Ile Phe Ile Ser His
355 360 365
Lys Lys Leu Glu Thr Ile Ser Ser Ala Leu Cys Asp His Trp Asp Thr
370 375 380
Leu Arg Asn Ala Leu Tyr Glu Arg Arg Ile Ser Glu Leu Thr Gly Lys
385 390 395 400
Ile Thr Lys Ser Ala Lys Glu Lys Val Gln Arg Ser Leu Lys His Glu
405 410 415
Asp Ile Asn Leu Gln Glu Ile Ile Ser Ala Ala Gly Lys Glu Leu Ser
420 425 430
Glu Ala Phe Lys Gln Lys Thr Ser Glu Ile Leu Ser His Ala His Ala
435 440 445
Ala Leu Asp Gln Pro Leu Pro Thr Thr Leu Lys Lys Gln Glu Glu Lys
450 455 460
Glu Ile Leu Lys Ser Gln Leu Asp Ser Leu Leu Gly Leu Tyr His Leu
465 470 475 480
Leu Asp Trp Phe Ala Val Asp Glu Ser Asn Glu Val Asp Pro Glu Phe
485 490 495
Ser Ala Arg Leu Thr Gly Ile Lys Leu Glu Met Glu Pro Ser Leu Ser
500 505 510
Phe Tyr Asn Lys Ala Arg Asn Tyr Ala Thr Lys Lys Pro Tyr Ser Val
515 520 525
Glu Lys Phe Lys Leu Asn Phe Gln Met Pro Thr Leu Ala Ser Gly Trp
530 535 540
Asp Val Asn Lys Glu Lys Asn Asn Gly Ala Ile Leu Phe Val Lys Asn
545 550 555 560
Gly Leu Tyr Tyr Leu Gly Ile Met Pro Lys Gln Lys Gly Arg Tyr Lys
565 570 575
Ala Leu Ser Phe Glu Pro Thr Glu Lys Thr Ser Glu Gly Phe Asp Lys
580 585 590
Met Tyr Tyr Asp Tyr Phe Pro Asp Ala Ala Lys Met Ile Pro Lys Cys
595 600 605
Ser Thr Gln Leu Lys Ala Val Thr Ala His Phe Gln Thr His Thr Thr
610 615 620
Pro Ile Leu Leu Ser Asn Asn Phe Ile Glu Pro Leu Glu Ile Thr Lys
625 630 635 640
Glu Ile Tyr Asp Leu Asn Asn Pro Glu Lys Glu Pro Lys Lys Phe Gln
645 650 655
Thr Ala Tyr Ala Lys Lys Thr Gly Asp Gln Lys Gly Tyr Arg Glu Ala
660 665 670
Leu Cys Lys Trp Ile Asp Phe Thr Arg Asp Phe Leu Ser Lys Tyr Thr
675 680 685
Lys Thr Thr Ser Ile Asp Leu Ser Ser Leu Arg Pro Ser Ser Gln Tyr
690 695 700
Lys Asp Leu Gly Glu Tyr Tyr Ala Glu Leu Asn Pro Leu Leu Tyr His
705 710 715 720
Ile Ser Phe Gln Arg Ile Ala Glu Lys Glu Ile Met Asp Ala Val Glu
725 730 735
Thr Gly Lys Leu Tyr Leu Phe Gln Ile Tyr Asn Lys Asp Phe Ala Lys
740 745 750
Gly His His Gly Lys Pro Asn Leu His Thr Leu Tyr Trp Thr Gly Leu
755 760 765
Phe Ser Pro Glu Asn Leu Ala Lys Thr Ser Ile Lys Leu Asn Gly Gln
770 775 780
Ala Glu Leu Phe Tyr Arg Pro Lys Ser Arg Met Lys Arg Met Ala His
785 790 795 800
Arg Leu Gly Glu Lys Met Leu Asn Lys Lys Leu Lys Asp Gln Lys Thr
805 810 815
Pro Ile Pro Asp Thr Leu Tyr Gln Glu Leu Tyr Asp Tyr Val Asn His
820 825 830
Arg Leu Ser His Asp Leu Ser Asp Glu Ala Arg Ala Leu Leu Pro Asn
835 840 845
Val Ile Thr Lys Glu Val Ser His Glu Ile Ile Lys Asp Arg Arg Phe
850 855 860
Thr Ser Asp Lys Phe Phe Phe His Val Pro Ile Thr Leu Asn Tyr Gln
865 870 875 880
Ala Ala Asn Ser Pro Ser Lys Phe Asn Gln Arg Val Asn Ala Tyr Leu
885 890 895
Lys Glu His Pro Glu Thr Pro Ile Ile Gly Ile Asp Arg Gly Glu Arg
900 905 910
Asn Leu Ile Tyr Ile Thr Val Ile Asp Ser Thr Gly Lys Ile Leu Glu
915 920 925
Gln Arg Ser Leu Asn Thr Ile Gln Gln Phe Asp Tyr Gln Lys Lys Leu
930 935 940
Asp Asn Arg Glu Lys Glu Arg Val Ala Ala Arg Gln Ala Trp Ser Val
945 950 955 960
Val Gly Thr Ile Lys Asp Leu Lys Gln Gly Tyr Leu Ser Gln Val Ile
965 970 975
His Glu Ile Val Asp Leu Met Ile His Tyr Gln Ala Val Val Val Leu
980 985 990
Glu Asn Leu Asn Phe Gly Phe Lys Ser Lys Arg Thr Gly Ile Ala Glu
995 1000 1005
Lys Ala Val Tyr Gln Gln Phe Glu Lys Met Leu Ile Asp Lys Leu
1010 1015 1020
Asn Cys Leu Val Leu Lys Asp Tyr Pro Ala Glu Lys Val Gly Gly
1025 1030 1035
Val Leu Asn Pro Tyr Gln Leu Thr Asp Gln Phe Thr Ser Phe Ala
1040 1045 1050
Lys Met Gly Thr Gln Ser Gly Phe Leu Phe Tyr Val Pro Ala Pro
1055 1060 1065
Tyr Thr Ser Lys Ile Asp Pro Leu Thr Gly Phe Val Asp Pro Phe
1070 1075 1080
Val Trp Lys Thr Ile Lys Asn His Glu Ser Arg Lys His Phe Leu
1085 1090 1095
Glu Gly Phe Asp Phe Leu His Tyr Asp Val Lys Thr Gly Asp Phe
1100 1105 1110
Ile Leu His Phe Lys Met Asn Arg Asn Leu Ser Phe Gln Arg Gly
1115 1120 1125
Leu Pro Gly Phe Met Pro Ala Trp Asp Ile Val Phe Glu Lys Asn
1130 1135 1140
Glu Thr Gln Phe Asp Ala Lys Gly Thr Pro Phe Ile Ala Gly Lys
1145 1150 1155
Arg Ile Val Pro Val Ile Glu Asn His Arg Phe Thr Gly Arg Tyr
1160 1165 1170
Arg Asp Leu Tyr Pro Ala Asn Glu Leu Ile Ala Leu Leu Glu Glu
1175 1180 1185
Lys Gly Ile Val Phe Arg Asp Gly Ser Asn Ile Leu Pro Lys Leu
1190 1195 1200
Leu Glu Asn Asp Asp Ser His Ala Ile Asp Thr Met Val Ala Leu
1205 1210 1215
Ile Arg Ser Val Leu Gln Met Arg Asn Ser Asn Ala Ala Thr Gly
1220 1225 1230
Glu Asp Tyr Ile Asn Ser Pro Val Arg Asp Leu Asn Gly Val Cys
1235 1240 1245
Phe Asp Ser Arg Phe Gln Asn Pro Glu Trp Pro Met Asp Ala Asp
1250 1255 1260
Ala Asn Gly Ala Tyr His Ile Ala Leu Lys Gly Gln Leu Leu Leu
1265 1270 1275
Asn His Leu Lys Glu Ser Lys Asp Leu Lys Leu Gln Asn Gly Ile
1280 1285 1290
Ser Asn Gln Asp Trp Leu Ala Tyr Ile Gln Glu Leu Arg Asn
1295 1300 1305
<210> 175
<211> 28
<212> DNA
<213> 沙氏纤毛菌（Leptotrichia shahii）
<400> 175
ccaccccaat atcgaagggg actaaaac 28
<210> 176
<211> 36
<212> DNA
<213> 韦德纤毛菌（Leptotrichia wadei）
<400> 176
gatttagact accccaaaaa cgaaggggac taaaac 36
<210> 177
<211> 36
<212> DNA
<213> 西尔李斯特菌（Listeria seeligeri）
<400> 177
gtaagagact acctctatat gaaagaggac taaaac 36
<210> 178
<211> 35
<212> DNA
<213> 毛螺科（Lachnospiraceae）细菌MA2020
<400> 178
gtattgagaa aagccagata tagttggcaa tagac 35
<210> 179
<211> 35
<212> DNA
<213> 毛螺科（Lachnospiraceae）细菌NK4A179
<400> 179
gttgatgaga agagcccaag atagagggca ataac 35
<210> 180
<211> 35
<212> DNA
<213> 嗜氨基梭菌（Clostridium aminophilum）DSM 10710
<400> 180
gtctattgcc ctctatatcg ggctgttctc caaac 35
<210> 181
<211> 36
<212> DNA
<213> 鸡肉杆菌（Carnobacterium gallinarum）DSM 4847
<400> 181
attaaagact acctctaaat gtaagaggac tataac 36
<210> 182
<211> 36
<212> DNA
<213> 鸡肉杆菌（Carnobacterium gallinarum）DSM 4847
<400> 182
aatataaact acctctaaat gtaagaggac tataac 36
<210> 183
<211> 36
<212> DNA
<213> 产丙酸沼杆菌（Paludibacter propionicigenes）WB4
<400> 183
cttgtggatt atcccaaaat tgaagggaac tacaac 36
<210> 184
<211> 36
<212> DNA
<213> 韦氏李斯特菌（Listeria weihenstephanensis）FSL R9-0317
<400> 184
gatttagagt acctcaaaat agaagaggtc taaaac 36
<210> 185
<211> 36
<212> DNA
<213> 李斯特菌科（Listeriaceae）细菌FSL M6-0635
<400> 185
gatttagagt acctcaaaac aaaagaggac taaaac 36
<210> 186
<211> 36
<212> DNA
<213> 韦德纤毛菌（Leptotrichia wadei） F0279
<400> 186
gatatagata accccaaaaa cgaagggatc taaaac 36
<210> 187
<211> 36
<212> DNA
<213> 荚膜红细菌（Rhodobacter capsulatus）SB 1003
<400> 187
gcctcacatc accgccaaga cgacggcgga ctgaac 36
<210> 188
<211> 36
<212> DNA
<213> 荚膜红细菌（Rhodobacter capsulatus）R121
<400> 188
gcctcacatc accgccaaga cgacggcgga ctgaac 36
<210> 189
<211> 36
<212> DNA
<213> 荚膜红细菌（Rhodobacter capsulatus）DE442
<400> 189
gcctcacatc accgccaaga cgacggcgga ctgaac 36
<210> 190
<211> 1389
<212> PRT
<213> 未知的
<220>
<223> Cas13a
<400> 190
Met Gly Asn Leu Phe Gly His Lys Arg Trp Tyr Glu Val Arg Asp Lys
1 5 10 15
Lys Asp Phe Lys Ile Lys Arg Lys Val Lys Val Lys Arg Asn Tyr Asp
20 25 30
Gly Asn Lys Tyr Ile Leu Asn Ile Asn Glu Asn Asn Asn Lys Glu Lys
35 40 45
Ile Asp Asn Asn Lys Phe Ile Arg Lys Tyr Ile Asn Tyr Lys Lys Asn
50 55 60
Asp Asn Ile Leu Lys Glu Phe Thr Arg Lys Phe His Ala Gly Asn Ile
65 70 75 80
Leu Phe Lys Leu Lys Gly Lys Glu Gly Ile Ile Arg Ile Glu Asn Asn
85 90 95
Asp Asp Phe Leu Glu Thr Glu Glu Val Val Leu Tyr Ile Glu Ala Tyr
100 105 110
Gly Lys Ser Glu Lys Leu Lys Ala Leu Gly Ile Thr Lys Lys Lys Ile
115 120 125
Ile Asp Glu Ala Ile Arg Gln Gly Ile Thr Lys Asp Asp Lys Lys Ile
130 135 140
Glu Ile Lys Arg Gln Glu Asn Glu Glu Glu Ile Glu Ile Asp Ile Arg
145 150 155 160
Asp Glu Tyr Thr Asn Lys Thr Leu Asn Asp Cys Ser Ile Ile Leu Arg
165 170 175
Ile Ile Glu Asn Asp Glu Leu Glu Thr Lys Lys Ser Ile Tyr Glu Ile
180 185 190
Phe Lys Asn Ile Asn Met Ser Leu Tyr Lys Ile Ile Glu Lys Ile Ile
195 200 205
Glu Asn Glu Thr Glu Lys Val Phe Glu Asn Arg Tyr Tyr Glu Glu His
210 215 220
Leu Arg Glu Lys Leu Leu Lys Asp Asp Lys Ile Asp Val Ile Leu Thr
225 230 235 240
Asn Phe Met Glu Ile Arg Glu Lys Ile Lys Ser Asn Leu Glu Ile Leu
245 250 255
Gly Phe Val Lys Phe Tyr Leu Asn Val Gly Gly Asp Lys Lys Lys Ser
260 265 270
Lys Asn Lys Lys Met Leu Val Glu Lys Ile Leu Asn Ile Asn Val Asp
275 280 285
Leu Thr Val Glu Asp Ile Ala Asp Phe Val Ile Lys Glu Leu Glu Phe
290 295 300
Trp Asn Ile Thr Lys Arg Ile Glu Lys Val Lys Lys Val Asn Asn Glu
305 310 315 320
Phe Leu Glu Lys Arg Arg Asn Arg Thr Tyr Ile Lys Ser Tyr Val Leu
325 330 335
Leu Asp Lys His Glu Lys Phe Lys Ile Glu Arg Glu Asn Lys Lys Asp
340 345 350
Lys Ile Val Lys Phe Phe Val Glu Asn Ile Lys Asn Asn Ser Ile Lys
355 360 365
Glu Lys Ile Glu Lys Ile Leu Ala Glu Phe Lys Ile Asp Glu Leu Ile
370 375 380
Lys Lys Leu Glu Lys Glu Leu Lys Lys Gly Asn Cys Asp Thr Glu Ile
385 390 395 400
Phe Gly Ile Phe Lys Lys His Tyr Lys Val Asn Phe Asp Ser Lys Lys
405 410 415
Phe Ser Lys Lys Ser Asp Glu Glu Lys Glu Leu Tyr Lys Ile Ile Tyr
420 425 430
Arg Tyr Leu Lys Gly Arg Ile Glu Lys Ile Leu Val Asn Glu Gln Lys
435 440 445
Val Arg Leu Lys Lys Met Glu Lys Ile Glu Ile Glu Lys Ile Leu Asn
450 455 460
Glu Ser Ile Leu Ser Glu Lys Ile Leu Lys Arg Val Lys Gln Tyr Thr
465 470 475 480
Leu Glu His Ile Met Tyr Leu Gly Lys Leu Arg His Asn Asp Ile Asp
485 490 495
Met Thr Thr Val Asn Thr Asp Asp Phe Ser Arg Leu His Ala Lys Glu
500 505 510
Glu Leu Asp Leu Glu Leu Ile Thr Phe Phe Ala Ser Thr Asn Met Glu
515 520 525
Leu Asn Lys Ile Phe Ser Arg Glu Asn Ile Asn Asn Asp Glu Asn Ile
530 535 540
Asp Phe Phe Gly Gly Asp Arg Glu Lys Asn Tyr Val Leu Asp Lys Lys
545 550 555 560
Ile Leu Asn Ser Lys Ile Lys Ile Ile Arg Asp Leu Asp Phe Ile Asp
565 570 575
Asn Lys Asn Asn Ile Thr Asn Asn Phe Ile Arg Lys Phe Thr Lys Ile
580 585 590
Gly Thr Asn Glu Arg Asn Arg Ile Leu His Ala Ile Ser Lys Glu Arg
595 600 605
Asp Leu Gln Gly Thr Gln Asp Asp Tyr Asn Lys Val Ile Asn Ile Ile
610 615 620
Gln Asn Leu Lys Ile Ser Asp Glu Glu Val Ser Lys Ala Leu Asn Leu
625 630 635 640
Asp Val Val Phe Lys Asp Lys Lys Asn Ile Ile Thr Lys Ile Asn Asp
645 650 655
Ile Lys Ile Ser Glu Glu Asn Asn Asn Asp Ile Lys Tyr Leu Pro Ser
660 665 670
Phe Ser Lys Val Leu Pro Glu Ile Leu Asn Leu Tyr Arg Asn Asn Pro
675 680 685
Lys Asn Glu Pro Phe Asp Thr Ile Glu Thr Glu Lys Ile Val Leu Asn
690 695 700
Ala Leu Ile Tyr Val Asn Lys Glu Leu Tyr Lys Lys Leu Ile Leu Glu
705 710 715 720
Asp Asp Leu Glu Glu Asn Glu Ser Lys Asn Ile Phe Leu Gln Glu Leu
725 730 735
Lys Lys Thr Leu Gly Asn Ile Asp Glu Ile Asp Glu Asn Ile Ile Glu
740 745 750
Asn Tyr Tyr Lys Asn Ala Gln Ile Ser Ala Ser Lys Gly Asn Asn Lys
755 760 765
Ala Ile Lys Lys Tyr Gln Lys Lys Val Ile Glu Cys Tyr Ile Gly Tyr
770 775 780
Leu Arg Lys Asn Tyr Glu Glu Leu Phe Asp Phe Ser Asp Phe Lys Met
785 790 795 800
Asn Ile Gln Glu Ile Lys Lys Gln Ile Lys Asp Ile Asn Asp Asn Lys
805 810 815
Thr Tyr Glu Arg Ile Thr Val Lys Thr Ser Asp Lys Thr Ile Val Ile
820 825 830
Asn Asp Asp Phe Glu Tyr Ile Ile Ser Ile Phe Ala Leu Leu Asn Ser
835 840 845
Asn Ala Val Ile Asn Lys Ile Arg Asn Arg Phe Phe Ala Thr Ser Val
850 855 860
Trp Leu Asn Thr Ser Glu Tyr Gln Asn Ile Ile Asp Ile Leu Asp Glu
865 870 875 880
Ile Met Gln Leu Asn Thr Leu Arg Asn Glu Cys Ile Thr Glu Asn Trp
885 890 895
Asn Leu Asn Leu Glu Glu Phe Ile Gln Lys Met Lys Glu Ile Glu Lys
900 905 910
Asp Phe Asp Asp Phe Lys Ile Gln Thr Lys Lys Glu Ile Phe Asn Asn
915 920 925
Tyr Tyr Glu Asp Ile Lys Asn Asn Ile Leu Thr Glu Phe Lys Asp Asp
930 935 940
Ile Asn Gly Cys Asp Val Leu Glu Lys Lys Leu Glu Lys Ile Val Ile
945 950 955 960
Phe Asp Asp Glu Thr Lys Phe Glu Ile Asp Lys Lys Ser Asn Ile Leu
965 970 975
Gln Asp Glu Gln Arg Lys Leu Ser Asn Ile Asn Lys Lys Asp Leu Lys
980 985 990
Lys Lys Val Asp Gln Tyr Ile Lys Asp Lys Asp Gln Glu Ile Lys Ser
995 1000 1005
Lys Ile Leu Cys Arg Ile Ile Phe Asn Ser Asp Phe Leu Lys Lys
1010 1015 1020
Tyr Lys Lys Glu Ile Asp Asn Leu Ile Glu Asp Met Glu Ser Glu
1025 1030 1035
Asn Glu Asn Lys Phe Gln Glu Ile Tyr Tyr Pro Lys Glu Arg Lys
1040 1045 1050
Asn Glu Leu Tyr Ile Tyr Lys Lys Asn Leu Phe Leu Asn Ile Gly
1055 1060 1065
Asn Pro Asn Phe Asp Lys Ile Tyr Gly Leu Ile Ser Asn Asp Ile
1070 1075 1080
Lys Met Ala Asp Ala Lys Phe Leu Phe Asn Ile Asp Gly Lys Asn
1085 1090 1095
Ile Arg Lys Asn Lys Ile Ser Glu Ile Asp Ala Ile Leu Lys Asn
1100 1105 1110
Leu Asn Asp Lys Leu Asn Gly Tyr Ser Lys Glu Tyr Lys Glu Lys
1115 1120 1125
Tyr Ile Lys Lys Leu Lys Glu Asn Asp Asp Phe Phe Ala Lys Asn
1130 1135 1140
Ile Gln Asn Lys Asn Tyr Lys Ser Phe Glu Lys Asp Tyr Asn Arg
1145 1150 1155
Val Ser Glu Tyr Lys Lys Ile Arg Asp Leu Val Glu Phe Asn Tyr
1160 1165 1170
Leu Asn Lys Ile Glu Ser Tyr Leu Ile Asp Ile Asn Trp Lys Leu
1175 1180 1185
Ala Ile Gln Met Ala Arg Phe Glu Arg Asp Met His Tyr Ile Val
1190 1195 1200
Asn Gly Leu Arg Glu Leu Gly Ile Ile Lys Leu Ser Gly Tyr Asn
1205 1210 1215
Thr Gly Ile Ser Arg Ala Tyr Pro Lys Arg Asn Gly Ser Asp Gly
1220 1225 1230
Phe Tyr Thr Thr Thr Ala Tyr Tyr Lys Phe Phe Asp Glu Glu Ser
1235 1240 1245
Tyr Lys Lys Phe Glu Lys Ile Cys Tyr Gly Phe Gly Ile Asp Leu
1250 1255 1260
Ser Glu Asn Ser Glu Ile Asn Lys Pro Glu Asn Glu Ser Ile Arg
1265 1270 1275
Asn Tyr Ile Ser His Phe Tyr Ile Val Arg Asn Pro Phe Ala Asp
1280 1285 1290
Tyr Ser Ile Ala Glu Gln Ile Asp Arg Val Ser Asn Leu Leu Ser
1295 1300 1305
Tyr Ser Thr Arg Tyr Asn Asn Ser Thr Tyr Ala Ser Val Phe Glu
1310 1315 1320
Val Phe Lys Lys Asp Val Asn Leu Asp Tyr Asp Glu Leu Lys Lys
1325 1330 1335
Lys Phe Lys Leu Ile Gly Asn Asn Asp Ile Leu Glu Arg Leu Met
1340 1345 1350
Lys Pro Lys Lys Val Ser Val Leu Glu Leu Glu Ser Tyr Asn Ser
1355 1360 1365
Asp Tyr Ile Lys Asn Leu Ile Ile Glu Leu Leu Thr Lys Ile Glu
1370 1375 1380
Asn Thr Asn Asp Thr Leu
1385
<210> 191
<211> 1221
<212> PRT
<213> 动物溃疡伯格菌（Bergeyella zoohelcum）ATCC 43767
<400> 191
Met Glu Asn Lys Thr Ser Leu Gly Asn Asn Ile Tyr Tyr Asn Pro Phe
1 5 10 15
Lys Pro Gln Asp Lys Ser Tyr Phe Ala Gly Tyr Phe Asn Ala Ala Met
20 25 30
Glu Asn Thr Asp Ser Val Phe Arg Glu Leu Gly Lys Arg Leu Lys Gly
35 40 45
Lys Glu Tyr Thr Ser Glu Asn Phe Phe Asp Ala Ile Phe Lys Glu Asn
50 55 60
Ile Ser Leu Val Glu Tyr Glu Arg Tyr Val Lys Leu Leu Ser Asp Tyr
65 70 75 80
Phe Pro Met Ala Arg Leu Leu Asp Lys Lys Glu Val Pro Ile Lys Glu
85 90 95
Arg Lys Glu Asn Phe Lys Lys Asn Phe Lys Gly Ile Ile Lys Ala Val
100 105 110
Arg Asp Leu Arg Asn Phe Tyr Thr His Lys Glu His Gly Glu Val Glu
115 120 125
Ile Thr Asp Glu Ile Phe Gly Val Leu Asp Glu Met Leu Lys Ser Thr
130 135 140
Val Leu Thr Val Lys Lys Lys Lys Val Lys Thr Asp Lys Thr Lys Glu
145 150 155 160
Ile Leu Lys Lys Ser Ile Glu Lys Gln Leu Asp Ile Leu Cys Gln Lys
165 170 175
Lys Leu Glu Tyr Leu Arg Asp Thr Ala Arg Lys Ile Glu Glu Lys Arg
180 185 190
Arg Asn Gln Arg Glu Arg Gly Glu Lys Glu Leu Val Ala Pro Phe Lys
195 200 205
Tyr Ser Asp Lys Arg Asp Asp Leu Ile Ala Ala Ile Tyr Asn Asp Ala
210 215 220
Phe Asp Val Tyr Ile Asp Lys Lys Lys Asp Ser Leu Lys Glu Ser Ser
225 230 235 240
Lys Ala Lys Tyr Asn Thr Lys Ser Asp Pro Gln Gln Glu Glu Gly Asp
245 250 255
Leu Lys Ile Pro Ile Ser Lys Asn Gly Val Val Phe Leu Leu Ser Leu
260 265 270
Phe Leu Thr Lys Gln Glu Ile His Ala Phe Lys Ser Lys Ile Ala Gly
275 280 285
Phe Lys Ala Thr Val Ile Asp Glu Ala Thr Val Ser Glu Ala Thr Val
290 295 300
Ser His Gly Lys Asn Ser Ile Cys Phe Met Ala Thr His Glu Ile Phe
305 310 315 320
Ser His Leu Ala Tyr Lys Lys Leu Lys Arg Lys Val Arg Thr Ala Glu
325 330 335
Ile Asn Tyr Gly Glu Ala Glu Asn Ala Glu Gln Leu Ser Val Tyr Ala
340 345 350
Lys Glu Thr Leu Met Met Gln Met Leu Asp Glu Leu Ser Lys Val Pro
355 360 365
Asp Val Val Tyr Gln Asn Leu Ser Glu Asp Val Gln Lys Thr Phe Ile
370 375 380
Glu Asp Trp Asn Glu Tyr Leu Lys Glu Asn Asn Gly Asp Val Gly Thr
385 390 395 400
Met Glu Glu Glu Gln Val Ile His Pro Val Ile Arg Lys Arg Tyr Glu
405 410 415
Asp Lys Phe Asn Tyr Phe Ala Ile Arg Phe Leu Asp Glu Phe Ala Gln
420 425 430
Phe Pro Thr Leu Arg Phe Gln Val His Leu Gly Asn Tyr Leu His Asp
435 440 445
Ser Arg Pro Lys Glu Asn Leu Ile Ser Asp Arg Arg Ile Lys Glu Lys
450 455 460
Ile Thr Val Phe Gly Arg Leu Ser Glu Leu Glu His Lys Lys Ala Leu
465 470 475 480
Phe Ile Lys Asn Thr Glu Thr Asn Glu Asp Arg Glu His Tyr Trp Glu
485 490 495
Ile Phe Pro Asn Pro Asn Tyr Asp Phe Pro Lys Glu Asn Ile Ser Val
500 505 510
Asn Asp Lys Asp Phe Pro Ile Ala Gly Ser Ile Leu Asp Arg Glu Lys
515 520 525
Gln Pro Val Ala Gly Lys Ile Gly Ile Lys Val Lys Leu Leu Asn Gln
530 535 540
Gln Tyr Val Ser Glu Val Asp Lys Ala Val Lys Ala His Gln Leu Lys
545 550 555 560
Gln Arg Lys Ala Ser Lys Pro Ser Ile Gln Asn Ile Ile Glu Glu Ile
565 570 575
Val Pro Ile Asn Glu Ser Asn Pro Lys Glu Ala Ile Val Phe Gly Gly
580 585 590
Gln Pro Thr Ala Tyr Leu Ser Met Asn Asp Ile His Ser Ile Leu Tyr
595 600 605
Glu Phe Phe Asp Lys Trp Glu Lys Lys Lys Glu Lys Leu Glu Lys Lys
610 615 620
Gly Glu Lys Glu Leu Arg Lys Glu Ile Gly Lys Glu Leu Glu Lys Lys
625 630 635 640
Ile Val Gly Lys Ile Gln Ala Gln Ile Gln Gln Ile Ile Asp Lys Asp
645 650 655
Thr Asn Ala Lys Ile Leu Lys Pro Tyr Gln Asp Gly Asn Ser Thr Ala
660 665 670
Ile Asp Lys Glu Lys Leu Ile Lys Asp Leu Lys Gln Glu Gln Asn Ile
675 680 685
Leu Gln Lys Leu Lys Asp Glu Gln Thr Val Arg Glu Lys Glu Tyr Asn
690 695 700
Asp Phe Ile Ala Tyr Gln Asp Lys Asn Arg Glu Ile Asn Lys Val Arg
705 710 715 720
Asp Arg Asn His Lys Gln Tyr Leu Lys Asp Asn Leu Lys Arg Lys Tyr
725 730 735
Pro Glu Ala Pro Ala Arg Lys Glu Val Leu Tyr Tyr Arg Glu Lys Gly
740 745 750
Lys Val Ala Val Trp Leu Ala Asn Asp Ile Lys Arg Phe Met Pro Thr
755 760 765
Asp Phe Lys Asn Glu Trp Lys Gly Glu Gln His Ser Leu Leu Gln Lys
770 775 780
Ser Leu Ala Tyr Tyr Glu Gln Cys Lys Glu Glu Leu Lys Asn Leu Leu
785 790 795 800
Pro Glu Lys Val Phe Gln His Leu Pro Phe Lys Leu Gly Gly Tyr Phe
805 810 815
Gln Gln Lys Tyr Leu Tyr Gln Phe Tyr Thr Cys Tyr Leu Asp Lys Arg
820 825 830
Leu Glu Tyr Ile Ser Gly Leu Val Gln Gln Ala Glu Asn Phe Lys Ser
835 840 845
Glu Asn Lys Val Phe Lys Lys Val Glu Asn Glu Cys Phe Lys Phe Leu
850 855 860
Lys Lys Gln Asn Tyr Thr His Lys Glu Leu Asp Ala Arg Val Gln Ser
865 870 875 880
Ile Leu Gly Tyr Pro Ile Phe Leu Glu Arg Gly Phe Met Asp Glu Lys
885 890 895
Pro Thr Ile Ile Lys Gly Lys Thr Phe Lys Gly Asn Glu Ala Leu Phe
900 905 910
Ala Asp Trp Phe Arg Tyr Tyr Lys Glu Tyr Gln Asn Phe Gln Thr Phe
915 920 925
Tyr Asp Thr Glu Asn Tyr Pro Leu Val Glu Leu Glu Lys Lys Gln Ala
930 935 940
Asp Arg Lys Arg Lys Thr Lys Ile Tyr Gln Gln Lys Lys Asn Asp Val
945 950 955 960
Phe Thr Leu Leu Met Ala Lys His Ile Phe Lys Ser Val Phe Lys Gln
965 970 975
Asp Ser Ile Asp Gln Phe Ser Leu Glu Asp Leu Tyr Gln Ser Arg Glu
980 985 990
Glu Arg Leu Gly Asn Gln Glu Arg Ala Arg Gln Thr Gly Glu Arg Asn
995 1000 1005
Thr Asn Tyr Ile Trp Asn Lys Thr Val Asp Leu Lys Leu Cys Asp
1010 1015 1020
Gly Lys Ile Thr Val Glu Asn Val Lys Leu Lys Asn Val Gly Asp
1025 1030 1035
Phe Ile Lys Tyr Glu Tyr Asp Gln Arg Val Gln Ala Phe Leu Lys
1040 1045 1050
Tyr Glu Glu Asn Ile Glu Trp Gln Ala Phe Leu Ile Lys Glu Ser
1055 1060 1065
Lys Glu Glu Glu Asn Tyr Pro Tyr Val Val Glu Arg Glu Ile Glu
1070 1075 1080
Gln Tyr Glu Lys Val Arg Arg Glu Glu Leu Leu Lys Glu Val His
1085 1090 1095
Leu Ile Glu Glu Tyr Ile Leu Glu Lys Val Lys Asp Lys Glu Ile
1100 1105 1110
Leu Lys Lys Gly Asp Asn Gln Asn Phe Lys Tyr Tyr Ile Leu Asn
1115 1120 1125
Gly Leu Leu Lys Gln Leu Lys Asn Glu Asp Val Glu Ser Tyr Lys
1130 1135 1140
Val Phe Asn Leu Asn Thr Glu Pro Glu Asp Val Asn Ile Asn Gln
1145 1150 1155
Leu Lys Gln Glu Ala Thr Asp Leu Glu Gln Lys Ala Phe Val Leu
1160 1165 1170
Thr Tyr Ile Arg Asn Lys Phe Ala His Asn Gln Leu Pro Lys Lys
1175 1180 1185
Glu Phe Trp Asp Tyr Cys Gln Glu Lys Tyr Gly Lys Glu Lys Thr
1190 1195 1200
Tyr Ala Glu Tyr Phe Ala Glu Val Phe Lys Lys Glu Lys Glu Ala
1205 1210 1215
Leu Ile Lys
1220
<210> 192
<211> 21
<212> DNA
<213> 人工序列
<220>
<223> GAPDH F引物
<400> 192
cagcctcaag atcatcagca a 21
<210> 193
<211> 20
<212> DNA
<213> 人工序列
<220>
<223> GAPDH R引物
<400> 193
tgtggtcatg agtccttcca 20
<210> 194
<211> 20
<212> DNA
<213> 人工序列
<220>
<223> NS5 F引物
<400> 194
gaggagagtg ccagagttgt 20
<210> 195
<211> 20
<212> DNA
<213> 人工序列
<220>
<223> NS5 R引物
<400> 195
tctctctccc catccagtga 20
<210> 196
<211> 23
<212> DNA
<213> 人工序列
<220>
<223> 靶向NS5的间隔子1
<400> 196
gcaatgatct tcatgttggg agc 23
<210> 197
<211> 22
<212> DNA
<213> 人工序列
<220>
<223> 靶向NS5的间隔子2
<400> 197
gaaccttgtt gatgaactct tc 22
<210> 198
<211> 22
<212> DNA
<213> 人工序列
<220>
<223> 靶向NS5的间隔子3
<400> 198
gttggtgatt agagcttcat tc 22
<210> 199
<211> 23
<212> DNA
<213> 人工序列
<220>
<223> 靶向NS5的间隔子4
<400> 199
gagtgatcct cgttcaagaa tcc 23
<210> 200
<211> 20
<212> DNA
<213> 人工序列
<220>
<223> 非靶向对照间隔子（λ2）
<400> 200
gtgataagtg gaatgccatg 20
<210> 201
<211> 114
<212> DNA
<213> 人工序列
<220>
<223> sgRNA支架
<220>
<221> 尚未归类的特征
<222> (2)..(21)
<223> n是a、c、g、t或u
<400> 201
gnnnnnnnnn nnnnnnnnnn nguuuaagag cuaugcugga aacagcauag caaguuuaaa 60
uaaggcuagu ccguuaucaa cuugaaaaag uggcaccgag ucggugcuuu uuuu 114
<210> 202
<211> 4991
<212> DNA
<213> 人工序列
<220>
<223> E43-CjeCas9和sgRNA质粒
<220>
<221> 尚未归类的特征
<222> (297)..(315)
<223> n是a、c、g、t或u
<400> 202
gtttattaca gggacagcag agatccagtt tggttaatta aggtaccgag ggcctatttc 60
ccatgattcc ttcatatttg catatacgat acaaggctgt tagagagata attagaatta 120
atttgactgt aaacacaaag atattagtac aaaatacgtg acgtagaaag taataatttc 180
ttgggtagtt tgcagtttta aaattatgtt ttaaaatgga ctatcatatg cttaccgtaa 240
cttgaaagta tttcgatttc ttggctttat atatcttgtg gaaaggacga aacaccnnnn 300
nnnnnnnnnn nnnnngtttt agtccctgaa gggactaaaa taaagagttt gcgggactct 360
gcggggttac aatcccctaa aaccgctttt tttcctgcag cccgggggat ccactagttc 420
tagagcggcc gccaccgcgg tggagctcca gcttttgttc cctttagtga gggttaattg 480
cgcgaattcg ctagctaggt cttgaaagga gtgggaattg gctccggtgc ccgtcagtgg 540
gcagagcgca catcgcccac agtccccgag aagttggggg gaggggtcgg caattgatcc 600
ggtgcctaga gaaggtggcg cggggtaaac tgggaaagtg atgtcgtgta ctggctccgc 660
ctttttcccg agggtggggg agaaccgtat ataagtgcag tagtcgccgt gaacgttctt 720
tttcgcaacg ggtttgccgc cagaacacag gaccggttct agagcgctat ttagaaccat 780
gtgttctccc caagaatctg gcatgaccgc tctttcagcg aggatgttga cgcgaagcag 840
atccctggga cctggggccg ggccacgagg gtgtcgggaa gaaccaggac cgttgcgacg 900
gagggaagca gcagcggaag ctcggaaatc ccattctccg gttaaacgac cccgcaaggc 960
acaacggctc agggttgctt acgaggggag cgattccgaa aagggtgaag gagcagagcc 1020
cttgaaggtt ccagtatggg aaccccagga ttggcagcag cagcttgtaa acatccgagc 1080
aatgaggaac aaaaaagatg cacctgttga tcacctcgga accgaacatt gttatgattc 1140
tagtgcgccg ccaaaagtcc gccggtatca ggttctgttg agtttgatgc tgagtagtca 1200
gactaaggac caggttacgg ccggagcaat gcaacggctt cgggcacggg gactcacggt 1260
cgatagcatt ttgcagaccg atgacgcaac attgggtaaa ctcatatatc cagttggctt 1320
ctggcggagc aaagtgaagt acatcaagca gacctcagcc attctccaac aacattacgg 1380
aggtgatata cccgcaagcg tagctgaact ggtagcactg ccgggcgtcg gtcccaaaat 1440
ggcacatctg gctatggcgg ttgcttgggg aacggtgtct ggtatcgcag ttgatacgca 1500
tgtccaccgc atcgccaatc ggctgaggtg gactaaaaaa gccactaagt ctcctgaaga 1560
aacacgggct gctctggaag agtggcttcc acgagagctg tggcatgaaa tcaatggatt 1620
gctggttggt ttcgggcagc agacatgctt gcccgtgcac ccccggtgtc atgcttgctt 1680
gaaccaggct ttgtgcccag ctgcccaggg cctgagtgga agtgagacac cgggaacatc 1740
tgagtctgcg accccggaga gcacaaacgc gcgaatcctg gccttcgcga ttggcattag 1800
cagcatcggc tgggcattct ctgaaaacga cgaactgaag gattgcggcg tgcgaatttt 1860
cactaaggtc gaaaatccca aaactggtga atcactcgct ctccctagac gactggcacg 1920
ctccgcacga aagaggcttg cccgccgcaa ggcacgcttg aaccatctta aacaccttat 1980
tgcaaatgag tttaaactga attatgagga ctaccaatcc tttgacgagt ctcttgctaa 2040
agcctacaaa gggagcctta tatccccgta tgagctccgg ttcagagcac tcaacgaact 2100
gctgtccaaa caggattttg ctcgcgtgat tctccacata gcgaagaggc gaggatacga 2160
tgacattaaa aacagtgatg ataaggaaaa aggggccata ctcaaagcga ttaagcaaaa 2220
tgaagagaag ctcgctaact atcaatcagt aggggagtat ctctataaag agtacttcca 2280
gaagttcaaa gaaaatagca aggaatttac taatgtccgg aataaaaagg agtcttacga 2340
aagatgtatt gcgcaatctt tcctcaagga cgagctcaaa ttgattttca agaaacaaag 2400
ggaatttggg ttcagcttct caaaaaaatt tgaggaagag gttctgagcg ttgcctttta 2460
caaacgcgcc cttaaggact tctcacatct cgtagggaat tgtagtttct tcaccgatga 2520
aaaacgggcg ccaaaaaata gccctttggc ttttatgttt gtcgctctga ctcgcatcat 2580
taatctgctc aacaacctta aaaacacgga agggattctg tacacaaagg atgatctgaa 2640
cgctctgctt aacgaagttt tgaagaacgg gactttgacc tacaaacaaa ccaaaaagct 2700
tcttggtctc agtgatgact acgaattcaa gggagaaaaa gggacatatt tcatcgaatt 2760
caagaagtat aaggagttca tcaaagcctt gggcgagcac aacttgtctc aagatgatct 2820
caacgaaatt gctaaggata tcactctgat taaagacgag atcaagctca aaaaggcgtt 2880
ggcgaagtat gaccttaacc aaaaccaaat agatagcctc agcaagttgg aatttaaaga 2940
tcacttgaat ataagtttca aggcccttaa gttggtcacc cccttgatgc ttgaaggaaa 3000
gaaatatgat gaggcatgta atgagctgaa tctcaaggtt gctattaacg aagacaaaaa 3060
agatttcctc ccagctttca atgagactta ctataaggac gaggttacca atcctgtggt 3120
gctccgagcc atcaaagagt atcgaaaggt cctgaatgct ttgctcaaaa aatacggtaa 3180
ggtacacaaa ataaatattg agctcgcaag ggaggtcggt aagaaccact cccagcgcgc 3240
caaaatagaa aaggaacaga atgaaaatta caaagcgaaa aaggacgccg agctcgagtg 3300
cgaaaagctg ggcctgaaaa taaacagcaa gaacattctc aaactccgcc tcttcaaaga 3360
acaaaaagaa ttttgtgctt atagtggtga gaaaataaaa atctccgatc ttcaagacga 3420
gaagatgctc gaaatagacg cgatatatcc atatagcagg tcttttgacg attcttacat 3480
gaataaagtg cttgttttca ctaagcagaa tcaggaaaag ttgaatcaga ccccctttga 3540
ggcctttggc aacgactcag caaagtggca gaagatcgag gtcttggcta agaatcttcc 3600
tactaagaaa cagaaaagga tattggataa gaactataaa gacaaagaac aaaagaactt 3660
taaagaccgc aacctcaatg acaccagata catagcaaga ttggttctga actacacaaa 3720
agattatttg gacttcttgc cgctgtctga tgatgagaac acgaaactca acgacacgca 3780
aaaggggtct aaagtccacg tcgaagctaa atctgggatg ctcacctcag cattgaggca 3840
tacgtgggga ttctcagcaa aggaccgaaa caatcacctg caccatgcca ttgacgcagt 3900
tatcatagcg tatgccaata attcaatagt aaaagcgttt agcgacttca agaaggaaca 3960
agagtccaac agcgccgagc tctacgcaaa aaagattagt gaactcgact acaaaaacaa 4020
aagaaaattc tttgagccgt tcagcggatt tcgacagaag gtattggata aaatagatga 4080
aattttcgtg agcaaacccg aaaggaaaaa gccctcaggc gccttgcacg aagagacttt 4140
caggaaggaa gaggaattct accaaagcta cggcggaaaa gagggagttt tgaaggctct 4200
cgaacttgga aagattagga aggtgaacgg caagatagtg aaaaacggcg atatgttccg 4260
ggttgatatc ttcaaacata aaaaaacgaa taaattttat gctgtgccta tatacactat 4320
ggacttcgca cttaaggtcc tgccgaataa ggcggtagcc cgatctaaaa aaggcgaaat 4380
taaggactgg attttgatgg atgaaaatta cgagttctgc ttttctctct acaaggattc 4440
ccttatattg atacagacga aagatatgca ggaaccggaa ttcgtgtatt acaacgcttt 4500
tacttcctct acggtatctt tgattgtctc caaacatgac aacaaattcg aaacactcag 4560
taaaaaccaa aagattctct ttaaaaatgc gaacgagaaa gaagtaattg caaaatcaat 4620
tggcatccaa aatttgaaag tttttgaaaa atatatagta tctgccctcg gagaggttac 4680
taaagcggaa tttagacagc gagaggactt caaaaaatca ggtccaccca agaaaaaacg 4740
caaggtggaa gatccgaaga aaaagcgaaa agtggatgtg taacgttttc cgggacgccg 4800
gctggatgat cctccagcgc ggggatctca tgctggagtt cttcgcccac cccaacttgt 4860
ttattgcagc ttataatggt tacaaataaa gcaatagcat cacaaatttc acaaataaag 4920
catttttttc actgcattct agttgtggtt tgtccaaact catcaatgta tcttatcatg 4980
tctgtatacc g 4991
<210> 203
<211> 5270
<212> DNA
<213> 人工序列
<220>
<223> E67-CjeCas9和sgRNA质粒
<220>
<221> 尚未归类的特征
<222> (297)..(315)
<223> n是a、c、g、t或u
<400> 203
gtttattaca gggacagcag agatccagtt tggttaatta aggtaccgag ggcctatttc 60
ccatgattcc ttcatatttg catatacgat acaaggctgt tagagagata attagaatta 120
atttgactgt aaacacaaag atattagtac aaaatacgtg acgtagaaag taataatttc 180
ttgggtagtt tgcagtttta aaattatgtt ttaaaatgga ctatcatatg cttaccgtaa 240
cttgaaagta tttcgatttc ttggctttat atatcttgtg gaaaggacga aacaccnnnn 300
nnnnnnnnnn nnnnngtttt agtccctgaa gggactaaaa taaagagttt gcgggactct 360
gcggggttac aatcccctaa aaccgctttt tttcctgcag cccgggggat ccactagttc 420
tagagcggcc gccaccgcgg tggagctcca gcttttgttc cctttagtga gggttaattg 480
cgcgaattcg ctagctaggt cttgaaagga gtgggaattg gctccggtgc ccgtcagtgg 540
gcagagcgca catcgcccac agtccccgag aagttggggg gaggggtcgg caattgatcc 600
ggtgcctaga gaaggtggcg cggggtaaac tgggaaagtg atgtcgtgta ctggctccgc 660
ctttttcccg agggtggggg agaaccgtat ataagtgcag tagtcgccgt gaacgttctt 720
tttcgcaacg ggtttgccgc cagaacacag gaccggttct agagcgctat ttagaaccat 780
gcaggaggta atagcggggc ttgagcgatt tacctttgcc ttcgaaaaag acgtagagat 840
gcagaaggga accggcctgc tcccatttca aggtatggac aaatcagcat ctgccgtgtg 900
caattttttc accaagggtc tgtgtgaaaa ggggaagctc tgtccatttc gccatgatcg 960
cggagagaag atggtggtgt gtaagcactg gctgagaggg ctttgcaaaa aaggcgacca 1020
ctgcaaattt cttcaccaat atgacctgac tcgaatgcct gagtgttatt tttacagtaa 1080
gttcggtgac tgtagcaaca aagaatgcag cttcttgcat gtcaaaccag cattcaagtc 1140
acaggattgc ccgtggtacg atcagggttt ttgcaaggac ggtcccctct gcaaatatcg 1200
acacgtaccc agaattatgt gccttaatta cctggtcggc ttctgtcctg aagggccaaa 1260
atgtcagttt gctcaaaaaa ttcgcgagtt caaattgctc cctgggtcta aaatttggga 1320
accccaggat tggcagcagc agcttgtaaa catccgagca atgaggaaca aaaaagatgc 1380
acctgttgat cacctcggaa ccgaacattg ttatgattct agtgcgccgc caaaagtccg 1440
ccggtatcag gttctgttga gtttgatgct gagtagtcag actaaggacc aggttacggc 1500
cggagcaatg caacggcttc gggcacgggg actcacggtc gatagcattt tgcagaccga 1560
tgacgcaaca ttgggtaaac tcatatatcc agttggcttc tggcggagca aagtgaagta 1620
catcaagcag acctcagcca ttctccaaca acattacgga ggtgatatac ccgcaagcgt 1680
agctgaactg gtagcactgc cgggcgtcgg tcccaaaatg gcacatctgg ctatggcggt 1740
tgcttgggga acggtgtctg gtatcgcagt tgatacgcat gtccaccgca tcgccaatcg 1800
gctgaggtgg actaaaaaag ccactaagtc tcctgaagaa acacgggctg ctctggaaga 1860
gtggcttcca cgagagctgt ggcatgaaat caatggattg ctggttggtt tcgggcagca 1920
gacatgcttg cccgtgcacc cccggtgtca tgcttgcttg aaccaggctt tgtgcccagc 1980
tgcccagggc ctgagtggaa gtgagacacc gggaacatct gagtctgcga ccccggagag 2040
cacaaacgcg cgaatcctgg ccttcgcgat tggcattagc agcatcggct gggcattctc 2100
tgaaaacgac gaactgaagg attgcggcgt gcgaattttc actaaggtcg aaaatcccaa 2160
aactggtgaa tcactcgctc tccctagacg actggcacgc tccgcacgaa agaggcttgc 2220
ccgccgcaag gcacgcttga accatcttaa acaccttatt gcaaatgagt ttaaactgaa 2280
ttatgaggac taccaatcct ttgacgagtc tcttgctaaa gcctacaaag ggagccttat 2340
atccccgtat gagctccggt tcagagcact caacgaactg ctgtccaaac aggattttgc 2400
tcgcgtgatt ctccacatag cgaagaggcg aggatacgat gacattaaaa acagtgatga 2460
taaggaaaaa ggggccatac tcaaagcgat taagcaaaat gaagagaagc tcgctaacta 2520
tcaatcagta ggggagtatc tctataaaga gtacttccag aagttcaaag aaaatagcaa 2580
ggaatttact aatgtccgga ataaaaagga gtcttacgaa agatgtattg cgcaatcttt 2640
cctcaaggac gagctcaaat tgattttcaa gaaacaaagg gaatttgggt tcagcttctc 2700
aaaaaaattt gaggaagagg ttctgagcgt tgccttttac aaacgcgccc ttaaggactt 2760
ctcacatctc gtagggaatt gtagtttctt caccgatgaa aaacgggcgc caaaaaatag 2820
ccctttggct tttatgtttg tcgctctgac tcgcatcatt aatctgctca acaaccttaa 2880
aaacacggaa gggattctgt acacaaagga tgatctgaac gctctgctta acgaagtttt 2940
gaagaacggg actttgacct acaaacaaac caaaaagctt cttggtctca gtgatgacta 3000
cgaattcaag ggagaaaaag ggacatattt catcgaattc aagaagtata aggagttcat 3060
caaagccttg ggcgagcaca acttgtctca agatgatctc aacgaaattg ctaaggatat 3120
cactctgatt aaagacgaga tcaagctcaa aaaggcgttg gcgaagtatg accttaacca 3180
aaaccaaata gatagcctca gcaagttgga atttaaagat cacttgaata taagtttcaa 3240
ggcccttaag ttggtcaccc ccttgatgct tgaaggaaag aaatatgatg aggcatgtaa 3300
tgagctgaat ctcaaggttg ctattaacga agacaaaaaa gatttcctcc cagctttcaa 3360
tgagacttac tataaggacg aggttaccaa tcctgtggtg ctccgagcca tcaaagagta 3420
tcgaaaggtc ctgaatgctt tgctcaaaaa atacggtaag gtacacaaaa taaatattga 3480
gctcgcaagg gaggtcggta agaaccactc ccagcgcgcc aaaatagaaa aggaacagaa 3540
tgaaaattac aaagcgaaaa aggacgccga gctcgagtgc gaaaagctgg gcctgaaaat 3600
aaacagcaag aacattctca aactccgcct cttcaaagaa caaaaagaat tttgtgctta 3660
tagtggtgag aaaataaaaa tctccgatct tcaagacgag aagatgctcg aaatagacgc 3720
gatatatcca tatagcaggt cttttgacga ttcttacatg aataaagtgc ttgttttcac 3780
taagcagaat caggaaaagt tgaatcagac cccctttgag gcctttggca acgactcagc 3840
aaagtggcag aagatcgagg tcttggctaa gaatcttcct actaagaaac agaaaaggat 3900
attggataag aactataaag acaaagaaca aaagaacttt aaagaccgca acctcaatga 3960
caccagatac atagcaagat tggttctgaa ctacacaaaa gattatttgg acttcttgcc 4020
gctgtctgat gatgagaaca cgaaactcaa cgacacgcaa aaggggtcta aagtccacgt 4080
cgaagctaaa tctgggatgc tcacctcagc attgaggcat acgtggggat tctcagcaaa 4140
ggaccgaaac aatcacctgc accatgccat tgacgcagtt atcatagcgt atgccaataa 4200
ttcaatagta aaagcgttta gcgacttcaa gaaggaacaa gagtccaaca gcgccgagct 4260
ctacgcaaaa aagattagtg aactcgacta caaaaacaaa agaaaattct ttgagccgtt 4320
cagcggattt cgacagaagg tattggataa aatagatgaa attttcgtga gcaaacccga 4380
aaggaaaaag ccctcaggcg ccttgcacga agagactttc aggaaggaag aggaattcta 4440
ccaaagctac ggcggaaaag agggagtttt gaaggctctc gaacttggaa agattaggaa 4500
ggtgaacggc aagatagtga aaaacggcga tatgttccgg gttgatatct tcaaacataa 4560
aaaaacgaat aaattttatg ctgtgcctat atacactatg gacttcgcac ttaaggtcct 4620
gccgaataag gcggtagccc gatctaaaaa aggcgaaatt aaggactgga ttttgatgga 4680
tgaaaattac gagttctgct tttctctcta caaggattcc cttatattga tacagacgaa 4740
agatatgcag gaaccggaat tcgtgtatta caacgctttt acttcctcta cggtatcttt 4800
gattgtctcc aaacatgaca acaaattcga aacactcagt aaaaaccaaa agattctctt 4860
taaaaatgcg aacgagaaag aagtaattgc aaaatcaatt ggcatccaaa atttgaaagt 4920
ttttgaaaaa tatatagtat ctgccctcgg agaggttact aaagcggaat ttagacagcg 4980
agaggacttc aaaaaatcag gtccacccaa gaaaaaacgc aaggtggaag atccgaagaa 5040
aaagcgaaaa gtggatgtgt aacgttttcc gggacgccgg ctggatgatc ctccagcgcg 5100
gggatctcat gctggagttc ttcgcccacc ccaacttgtt tattgcagct tataatggtt 5160
acaaataaag caatagcatc acaaatttca caaataaagc atttttttca ctgcattcta 5220
gttgtggttt gtccaaactc atcaatgtat cttatcatgt ctgtataccg 5270
<210> 204
<211> 137
<212> PRT
<213> 未知的
<220>
<223> RNA酶K
<400> 204
Met Gly Trp Leu Arg Pro Gly Pro Arg Pro Leu Cys Pro Pro Ala Arg
1 5 10 15
Ala Ser Trp Ala Phe Ser His Arg Phe Pro Ser Pro Leu Ala Pro Arg
20 25 30
Arg Ser Pro Thr Pro Phe Phe Met Ala Ser Leu Leu Cys Cys Gly Pro
35 40 45
Lys Leu Ala Ala Cys Gly Ile Val Leu Ser Ala Trp Gly Val Ile Met
50 55 60
Leu Ile Met Leu Gly Ile Phe Phe Asn Val His Ser Ala Val Leu Ile
65 70 75 80
Glu Asp Val Pro Phe Thr Glu Lys Asp Phe Glu Asn Gly Pro Gln Asn
85 90 95
Ile Tyr Asn Leu Tyr Glu Gln Val Ser Tyr Asn Cys Phe Ile Ala Ala
100 105 110
Gly Leu Tyr Leu Leu Leu Gly Gly Phe Ser Phe Cys Gln Val Arg Leu
115 120 125
Asn Lys Arg Lys Glu Tyr Met Val Arg
130 135
<210> 205
<211> 1245
<212> PRT
<213> 未知的
<220>
<223> TALEN
<400> 205
Met Arg Ile Gly Lys Ser Ser Gly Trp Leu Asn Glu Ser Val Ser Leu
1 5 10 15
Glu Tyr Glu His Val Ser Pro Pro Thr Arg Pro Arg Asp Thr Arg Arg
20 25 30
Arg Pro Arg Ala Ala Gly Asp Gly Gly Leu Ala His Leu His Arg Arg
35 40 45
Leu Ala Val Gly Tyr Ala Glu Asp Thr Pro Arg Thr Glu Ala Arg Ser
50 55 60
Pro Ala Pro Arg Arg Pro Leu Pro Val Ala Pro Ala Ser Ala Pro Pro
65 70 75 80
Ala Pro Ser Leu Val Pro Glu Pro Pro Met Pro Val Ser Leu Pro Ala
85 90 95
Val Ser Ser Pro Arg Phe Ser Ala Gly Ser Ser Ala Ala Ile Thr Asp
100 105 110
Pro Phe Pro Ser Leu Pro Pro Thr Pro Val Leu Tyr Ala Met Ala Arg
115 120 125
Glu Leu Glu Ala Leu Ser Asp Ala Thr Trp Gln Pro Ala Val Pro Leu
130 135 140
Pro Ala Glu Pro Pro Thr Asp Ala Arg Arg Gly Asn Thr Val Phe Asp
145 150 155 160
Glu Ala Ser Ala Ser Ser Pro Val Ile Ala Ser Ala Cys Pro Gln Ala
165 170 175
Phe Ala Ser Pro Pro Arg Ala Pro Arg Ser Ala Arg Ala Arg Arg Ala
180 185 190
Arg Thr Gly Gly Asp Ala Trp Pro Ala Pro Thr Phe Leu Ser Arg Pro
195 200 205
Ser Ser Ser Arg Ile Gly Arg Asp Val Phe Gly Lys Leu Val Ala Leu
210 215 220
Gly Tyr Ser Arg Glu Gln Ile Arg Lys Leu Lys Gln Glu Ser Leu Ser
225 230 235 240
Glu Ile Ala Lys Tyr His Thr Thr Leu Thr Gly Gln Gly Phe Thr His
245 250 255
Ala Asp Ile Cys Arg Ile Ser Arg Arg Arg Gln Ser Leu Arg Val Val
260 265 270
Ala Arg Asn Tyr Pro Glu Leu Ala Ala Ala Leu Pro Glu Leu Thr Arg
275 280 285
Ala His Ile Val Asp Ile Ala Arg Gln Arg Ser Gly Asp Leu Ala Leu
290 295 300
Gln Ala Leu Leu Pro Val Ala Thr Ala Leu Thr Ala Ala Pro Leu Arg
305 310 315 320
Leu Ser Ala Ser Gln Ile Ala Thr Val Ala Gln Tyr Gly Glu Arg Pro
325 330 335
Ala Ile Gln Ala Leu Tyr Arg Leu Arg Arg Lys Leu Thr Arg Ala Pro
340 345 350
Leu His Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Thr Gly
355 360 365
Gly Lys Arg Ala Leu Glu Ala Val Cys Val Gln Leu Pro Val Leu Arg
370 375 380
Ala Ala Pro Tyr Arg Leu Ser Thr Glu Gln Val Val Ala Ile Ala Ser
385 390 395 400
Asn Lys Gly Gly Lys Gln Ala Leu Glu Ala Val Lys Ala His Leu Leu
405 410 415
Asp Leu Leu Gly Ala Pro Tyr Val Leu Asp Thr Glu Gln Val Val Ala
420 425 430
Ile Ala Ser His Asn Gly Gly Lys Gln Ala Leu Glu Ala Val Lys Ala
435 440 445
Asp Leu Leu Asp Leu Arg Gly Ala Pro Tyr Ala Leu Ser Thr Glu Gln
450 455 460
Val Val Ala Ile Ala Ser His Asn Gly Gly Lys Gln Ala Leu Glu Ala
465 470 475 480
Val Lys Ala Asp Leu Leu Glu Leu Arg Gly Ala Pro Tyr Ala Leu Ser
485 490 495
Thr Glu Gln Val Val Ala Ile Ala Ser His Asn Gly Gly Lys Gln Ala
500 505 510
Leu Glu Ala Val Lys Ala His Leu Leu Asp Leu Arg Gly Val Pro Tyr
515 520 525
Ala Leu Ser Thr Glu Gln Val Val Ala Ile Ala Ser His Asn Gly Gly
530 535 540
Lys Gln Ala Leu Glu Ala Val Lys Ala Gln Leu Leu Asp Leu Arg Gly
545 550 555 560
Ala Pro Tyr Ala Leu Ser Thr Ala Gln Val Val Ala Ile Ala Ser Asn
565 570 575
Gly Gly Gly Lys Gln Ala Leu Glu Gly Ile Gly Glu Gln Leu Leu Lys
580 585 590
Leu Arg Thr Ala Pro Tyr Gly Leu Ser Thr Glu Gln Val Val Ala Ile
595 600 605
Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Ala Val Gly Ala Gln
610 615 620
Leu Val Ala Leu Arg Ala Ala Pro Tyr Ala Leu Ser Thr Glu Gln Val
625 630 635 640
Val Ala Ile Ala Ser Asn Lys Gly Gly Lys Gln Ala Leu Glu Ala Val
645 650 655
Lys Ala Gln Leu Leu Glu Leu Arg Gly Ala Pro Tyr Ala Leu Ser Thr
660 665 670
Ala Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Asn Gln Ala Leu
675 680 685
Glu Ala Val Gly Thr Gln Leu Val Ala Leu Arg Ala Ala Pro Tyr Ala
690 695 700
Leu Ser Thr Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys
705 710 715 720
Gln Ala Leu Glu Ala Val Gly Ala Gln Leu Val Ala Leu Arg Ala Ala
725 730 735
Pro Tyr Ala Leu Asn Thr Glu Gln Val Val Ala Ile Ala Ser Ser His
740 745 750
Gly Gly Lys Gln Ala Leu Glu Ala Val Arg Ala Leu Phe Pro Asp Leu
755 760 765
Arg Ala Ala Pro Tyr Ala Leu Ser Thr Ala Gln Leu Val Ala Ile Ala
770 775 780
Ser Asn Pro Gly Gly Lys Gln Ala Leu Glu Ala Val Arg Ala Leu Phe
785 790 795 800
Arg Glu Leu Arg Ala Ala Pro Tyr Ala Leu Ser Thr Glu Gln Val Val
805 810 815
Ala Ile Ala Ser Asn His Gly Gly Lys Gln Ala Leu Glu Ala Val Arg
820 825 830
Ala Leu Phe Arg Gly Leu Arg Ala Ala Pro Tyr Gly Leu Ser Thr Ala
835 840 845
Gln Val Val Ala Ile Ala Ser Ser Asn Gly Gly Lys Gln Ala Leu Glu
850 855 860
Ala Val Trp Ala Leu Leu Pro Val Leu Arg Ala Thr Pro Tyr Asp Leu
865 870 875 880
Asn Thr Ala Gln Ile Val Ala Ile Ala Ser His Asp Gly Gly Lys Pro
885 890 895
Ala Leu Glu Ala Val Trp Ala Lys Leu Pro Val Leu Arg Gly Ala Pro
900 905 910
Tyr Ala Leu Ser Thr Ala Gln Val Val Ala Ile Ala Cys Ile Ser Gly
915 920 925
Gln Gln Ala Leu Glu Ala Ile Glu Ala His Met Pro Thr Leu Arg Gln
930 935 940
Ala Ser His Ser Leu Ser Pro Glu Arg Val Ala Ala Ile Ala Cys Ile
945 950 955 960
Gly Gly Arg Ser Ala Val Glu Ala Val Arg Gln Gly Leu Pro Val Lys
965 970 975
Ala Ile Arg Arg Ile Arg Arg Glu Lys Ala Pro Val Ala Gly Pro Pro
980 985 990
Pro Ala Ser Leu Gly Pro Thr Pro Gln Glu Leu Val Ala Val Leu His
995 1000 1005
Phe Phe Arg Ala His Gln Gln Pro Arg Gln Ala Phe Val Asp Ala
1010 1015 1020
Leu Ala Ala Phe Gln Ala Thr Arg Pro Ala Leu Leu Arg Leu Leu
1025 1030 1035
Ser Ser Val Gly Val Thr Glu Ile Glu Ala Leu Gly Gly Thr Ile
1040 1045 1050
Pro Asp Ala Thr Glu Arg Trp Gln Arg Leu Leu Gly Arg Leu Gly
1055 1060 1065
Phe Arg Pro Ala Thr Gly Ala Ala Ala Pro Ser Pro Asp Ser Leu
1070 1075 1080
Gln Gly Phe Ala Gln Ser Leu Glu Arg Thr Leu Gly Ser Pro Gly
1085 1090 1095
Met Ala Gly Gln Ser Ala Cys Ser Pro His Arg Lys Arg Pro Ala
1100 1105 1110
Glu Thr Ala Ile Ala Pro Arg Ser Ile Arg Arg Ser Pro Asn Asn
1115 1120 1125
Ala Gly Gln Pro Ser Glu Pro Trp Pro Asp Gln Leu Ala Trp Leu
1130 1135 1140
Gln Arg Arg Lys Arg Thr Ala Arg Ser His Ile Arg Ala Asp Ser
1145 1150 1155
Ala Ala Ser Val Pro Ala Asn Leu His Leu Gly Thr Arg Ala Gln
1160 1165 1170
Phe Thr Pro Asp Arg Leu Arg Ala Glu Pro Gly Pro Ile Met Gln
1175 1180 1185
Ala His Thr Ser Pro Ala Ser Val Ser Phe Gly Ser His Val Ala
1190 1195 1200
Phe Glu Pro Gly Leu Pro Asp Pro Gly Thr Pro Thr Ser Ala Asp
1205 1210 1215
Leu Ala Ser Phe Glu Ala Glu Pro Phe Gly Val Gly Pro Leu Asp
1220 1225 1230
Phe His Leu Asp Trp Leu Leu Gln Ile Leu Glu Thr
1235 1240 1245
<210> 206
<211> 1373
<212> PRT
<213> 未知的
<220>
<223> TALEN
<400> 206
Met Asp Pro Ile Arg Ser Arg Thr Pro Ser Pro Ala Arg Glu Leu Leu
1 5 10 15
Pro Gly Pro Gln Pro Asp Arg Val Gln Pro Thr Ala Asp Arg Gly Gly
20 25 30
Ala Pro Pro Ala Gly Gly Pro Leu Asp Gly Leu Pro Ala Arg Arg Thr
35 40 45
Met Ser Arg Thr Arg Leu Pro Ser Pro Pro Ala Pro Ser Pro Ala Phe
50 55 60
Ser Ala Gly Ser Phe Ser Asp Leu Leu Arg Gln Phe Asp Pro Ser Leu
65 70 75 80
Leu Asp Thr Ser Leu Leu Asp Ser Met Pro Ala Val Gly Thr Pro His
85 90 95
Thr Ala Ala Ala Pro Ala Glu Cys Asp Glu Val Gln Ser Gly Leu Arg
100 105 110
Ala Ala Asp Asp Pro Pro Pro Thr Val Arg Val Ala Val Thr Ala Ala
115 120 125
Arg Pro Pro Arg Ala Lys Pro Ala Pro Arg Arg Arg Ala Ala Gln Pro
130 135 140
Ser Asp Ala Ser Pro Ala Ala Gln Val Asp Leu Arg Thr Leu Gly Tyr
145 150 155 160
Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys Val Gly Ser Thr Val
165 170 175
Ala Gln His His Glu Ala Leu Val Gly His Gly Phe Thr His Ala His
180 185 190
Ile Val Ala Leu Ser Arg His Pro Ala Ala Leu Gly Thr Val Ala Val
195 200 205
Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro Glu Ala Thr His Glu Asp
210 215 220
Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala Arg Ala Leu Glu Ala
225 230 235 240
Leu Leu Thr Val Ala Gly Glu Leu Arg Gly Pro Pro Leu Gln Leu Asp
245 250 255
Thr Gly Gln Leu Val Lys Ile Ala Lys Arg Gly Gly Val Thr Ala Val
260 265 270
Glu Ala Val His Ala Ser Arg Asn Ala Leu Thr Gly Ala Pro Leu Asn
275 280 285
Leu Thr Pro Ala Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys
290 295 300
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
305 310 315 320
His Gly Leu Thr Pro Ala Gln Val Val Ala Ile Ala Ser His Asp Gly
325 330 335
Gly Lys Gln Ala Leu Glu Thr Met Gln Arg Leu Leu Pro Val Leu Cys
340 345 350
Gln Ala His Gly Leu Pro Pro Asp Gln Val Val Ala Ile Ala Ser Asn
355 360 365
Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
370 375 380
Leu Cys Gln Ala His Gly Leu Thr Pro Asp Gln Val Val Ala Ile Ala
385 390 395 400
Ser His Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
405 410 415
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Asp Gln Val Val Ala
420 425 430
Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
435 440 445
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Asp Gln Val
450 455 460
Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val
465 470 475 480
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Asp
485 490 495
Gln Val Val Ala Ile Ala Ser Asn Gly Gly Lys Gln Ala Leu Glu Thr
500 505 510
Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro
515 520 525
Asp Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu
530 535 540
Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Thr His Gly Leu
545 550 555 560
Thr Pro Ala Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln
565 570 575
Ala Leu Glu Thr Val Gln Gln Leu Leu Pro Val Leu Cys Gln Ala His
580 585 590
Gly Leu Thr Pro Asp Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly
595 600 605
Lys Gln Ala Leu Ala Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln
610 615 620
Ala His Gly Leu Thr Pro Asp Gln Val Val Ala Ile Ala Ser Asn Gly
625 630 635 640
Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu
645 650 655
Cys Gln Ala His Gly Leu Thr Pro Asp Gln Val Val Ala Ile Ala Ser
660 665 670
Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro
675 680 685
Val Leu Cys Gln Ala His Gly Leu Thr Gln Val Gln Val Val Ala Ile
690 695 700
Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu
705 710 715 720
Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Ala Gln Val Val
725 730 735
Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln
740 745 750
Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Asp Gln
755 760 765
Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr
770 775 780
Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Gln
785 790 795 800
Glu Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu
805 810 815
Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu
820 825 830
Thr Pro Asp Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln
835 840 845
Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His
850 855 860
Gly Leu Thr Pro Ala Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly
865 870 875 880
Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln
885 890 895
Asp His Gly Leu Thr Leu Ala Gln Val Val Ala Ile Ala Ser Asn Ile
900 905 910
Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu
915 920 925
Cys Gln Ala His Gly Leu Thr Gln Asp Gln Val Val Ala Ile Ala Ser
930 935 940
Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro
945 950 955 960
Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val Ala Ile
965 970 975
Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu
980 985 990
Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Leu Asp Gln Val Val
995 1000 1005
Ala Ile Ala Ser Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln
1010 1015 1020
Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp
1025 1030 1035
Gln Val Val Ala Ile Ala Ser Asn Ser Gly Gly Lys Gln Ala Leu
1040 1045 1050
Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly
1055 1060 1065
Leu Thr Pro Asn Gln Val Val Ala Ile Ala Ser Asn Gly Gly Lys
1070 1075 1080
Gln Ala Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro
1085 1090 1095
Ala Leu Ala Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys
1100 1105 1110
Leu Gly Gly Arg Pro Ala Met Asp Ala Val Lys Lys Gly Leu Pro
1115 1120 1125
His Ala Pro Glu Leu Ile Arg Arg Val Asn Arg Arg Ile Gly Glu
1130 1135 1140
Arg Thr Ser His Arg Val Ala Asp Tyr Ala Gln Val Val Arg Val
1145 1150 1155
Leu Glu Phe Phe Gln Cys His Ser His Pro Ala Tyr Ala Phe Asp
1160 1165 1170
Glu Ala Met Thr Gln Phe Gly Met Ser Arg Asn Gly Leu Val Gln
1175 1180 1185
Leu Phe Arg Arg Val Gly Val Thr Glu Leu Glu Ala Arg Gly Gly
1190 1195 1200
Thr Leu Pro Pro Ala Ser Gln Arg Trp Asp Arg Ile Leu Gln Ala
1205 1210 1215
Ser Gly Met Lys Arg Ala Lys Pro Ser Pro Thr Ser Ala Gln Thr
1220 1225 1230
Pro Asp Gln Ala Ser Leu His Ala Phe Ala Asp Ser Leu Glu Arg
1235 1240 1245
Asp Leu Asp Ala Pro Ser Pro Met His Glu Gly Asp Gln Thr Gly
1250 1255 1260
Ala Ser Ser Arg Lys Arg Ser Arg Ser Asp Arg Ala Val Thr Gly
1265 1270 1275
Pro Ser Ala Gln His Ser Phe Glu Val Arg Val Pro Glu Gln Arg
1280 1285 1290
Asp Ala Leu His Leu Pro Leu Ser Trp Arg Val Lys Arg Pro Arg
1295 1300 1305
Thr Arg Ile Gly Gly Gly Leu Pro Asp Pro Gly Thr Pro Ile Ala
1310 1315 1320
Ala Asp Leu Ala Ala Ser Ser Thr Val Met Trp Glu Gln Asp Ala
1325 1330 1335
Ala Pro Phe Ala Gly Ala Ala Asp Asp Phe Pro Ala Phe Asn Glu
1340 1345 1350
Glu Glu Leu Ala Trp Leu Met Glu Leu Leu Pro Gln Ser Gly Ser
1355 1360 1365
Val Gly Gly Thr Ile
1370
<210> 207
<211> 1978
<212> PRT
<213> 未知的
<220>
<223> ZNF638
<400> 207
Met Ser Arg Pro Arg Phe Asn Pro Arg Gly Asp Phe Pro Leu Gln Arg
1 5 10 15
Pro Arg Ala Pro Asn Pro Ser Gly Met Arg Pro Pro Gly Pro Phe Met
20 25 30
Arg Pro Gly Ser Met Gly Leu Pro Arg Phe Tyr Pro Ala Gly Arg Ala
35 40 45
Arg Gly Ile Pro His Arg Phe Ala Gly His Glu Ser Tyr Gln Asn Met
50 55 60
Gly Pro Gln Arg Met Asn Val Gln Val Thr Gln His Arg Thr Asp Pro
65 70 75 80
Arg Leu Thr Lys Glu Lys Leu Asp Phe His Glu Ala Gln Gln Lys Lys
85 90 95
Gly Lys Pro His Gly Ser Arg Trp Asp Asp Glu Pro His Ile Ser Ala
100 105 110
Ser Val Ala Val Lys Gln Ser Ser Val Thr Gln Val Thr Glu Gln Ser
115 120 125
Pro Lys Val Gln Ser Arg Tyr Thr Lys Glu Ser Ala Ser Ser Ile Leu
130 135 140
Ala Ser Phe Gly Leu Ser Asn Glu Asp Leu Glu Glu Leu Ser Arg Tyr
145 150 155 160
Pro Asp Glu Gln Leu Thr Pro Glu Asn Met Pro Leu Ile Leu Arg Asp
165 170 175
Ile Arg Met Arg Lys Met Gly Arg Arg Leu Pro Asn Leu Pro Ser Gln
180 185 190
Ser Arg Asn Lys Glu Thr Leu Gly Ser Glu Ala Val Ser Ser Asn Val
195 200 205
Ile Asp Tyr Gly His Ala Ser Lys Tyr Gly Tyr Thr Glu Asp Pro Leu
210 215 220
Glu Val Arg Ile Tyr Asp Pro Glu Ile Pro Thr Asp Glu Val Glu Asn
225 230 235 240
Glu Phe Gln Ser Gln Gln Asn Ile Ser Ala Ser Val Pro Asn Pro Asn
245 250 255
Val Ile Cys Asn Ser Met Phe Pro Val Glu Asp Val Phe Arg Gln Met
260 265 270
Asp Phe Pro Gly Glu Ser Ser Asn Asn Arg Ser Phe Phe Ser Val Glu
275 280 285
Ser Gly Thr Lys Met Ser Gly Leu His Ile Ser Gly Gly Gln Ser Val
290 295 300
Leu Glu Pro Ile Lys Ser Val Asn Gln Ser Ile Asn Gln Thr Val Ser
305 310 315 320
Gln Thr Met Ser Gln Ser Leu Ile Pro Pro Ser Met Asn Gln Gln Pro
325 330 335
Phe Ser Ser Glu Leu Ile Ser Ser Val Ser Gln Gln Glu Arg Ile Pro
340 345 350
His Glu Pro Val Ile Asn Ser Ser Asn Val His Val Gly Ser Arg Gly
355 360 365
Ser Lys Lys Asn Tyr Gln Ser Gln Ala Asp Ile Pro Ile Arg Ser Pro
370 375 380
Phe Gly Ile Val Lys Ala Ser Trp Leu Pro Lys Phe Ser His Ala Asp
385 390 395 400
Ala Gln Lys Met Lys Arg Leu Pro Thr Pro Ser Met Met Asn Asp Tyr
405 410 415
Tyr Ala Ala Ser Pro Arg Ile Phe Pro His Leu Cys Ser Leu Cys Asn
420 425 430
Val Glu Cys Ser His Leu Lys Asp Trp Ile Gln His Gln Asn Thr Ser
435 440 445
Thr His Ile Glu Ser Cys Arg Gln Leu Arg Gln Gln Tyr Pro Asp Trp
450 455 460
Asn Pro Glu Ile Leu Pro Ser Arg Arg Asn Glu Gly Asn Arg Lys Glu
465 470 475 480
Asn Glu Thr Pro Arg Arg Arg Ser His Ser Pro Ser Pro Arg Arg Ser
485 490 495
Arg Arg Ser Ser Ser Ser His Arg Phe Arg Arg Ser Arg Ser Pro Met
500 505 510
His Tyr Met Tyr Arg Pro Arg Ser Arg Ser Pro Arg Ile Cys His Arg
515 520 525
Phe Ile Ser Arg Tyr Arg Ser Arg Ser Arg Ser Arg Ser Pro Tyr Arg
530 535 540
Ile Arg Asn Pro Phe Arg Gly Ser Pro Lys Cys Phe Arg Ser Val Ser
545 550 555 560
Pro Glu Arg Met Ser Arg Arg Ser Val Arg Ser Ser Asp Arg Lys Lys
565 570 575
Ala Leu Glu Asp Val Val Gln Arg Ser Gly His Gly Thr Glu Phe Asn
580 585 590
Lys Gln Lys His Leu Glu Ala Ala Asp Lys Gly His Ser Pro Ala Gln
595 600 605
Lys Pro Lys Thr Ser Ser Gly Thr Lys Pro Ser Val Lys Pro Thr Ser
610 615 620
Ala Thr Lys Ser Asp Ser Asn Leu Gly Gly His Ser Ile Arg Cys Lys
625 630 635 640
Ser Lys Asn Leu Glu Asp Asp Thr Leu Ser Glu Cys Lys Gln Val Ser
645 650 655
Asp Lys Ala Val Ser Leu Gln Arg Lys Leu Arg Lys Glu Gln Ser Leu
660 665 670
His Tyr Gly Ser Val Leu Leu Ile Thr Glu Leu Pro Glu Asp Gly Cys
675 680 685
Thr Glu Glu Asp Val Arg Lys Leu Phe Gln Pro Phe Gly Lys Val Asn
690 695 700
Asp Val Leu Ile Val Pro Tyr Arg Lys Glu Ala Tyr Leu Glu Met Glu
705 710 715 720
Phe Lys Glu Ala Ile Thr Ala Ile Met Lys Tyr Ile Glu Thr Thr Pro
725 730 735
Leu Thr Ile Lys Gly Lys Ser Val Lys Ile Cys Val Pro Gly Lys Lys
740 745 750
Lys Ala Gln Asn Lys Glu Val Lys Lys Lys Thr Leu Glu Ser Lys Lys
755 760 765
Val Ser Ala Ser Thr Leu Lys Arg Asp Ala Asp Ala Ser Lys Ala Val
770 775 780
Glu Ile Val Thr Ser Thr Ser Ala Ala Lys Thr Gly Gln Ala Lys Ala
785 790 795 800
Ser Val Ala Lys Val Asn Lys Ser Thr Gly Lys Ser Ala Ser Ser Val
805 810 815
Lys Ser Val Val Thr Val Ala Val Lys Gly Asn Lys Ala Ser Ile Lys
820 825 830
Thr Ala Lys Ser Gly Gly Lys Lys Ser Leu Glu Ala Lys Lys Thr Gly
835 840 845
Asn Val Lys Asn Lys Asp Ser Asn Lys Pro Val Thr Ile Pro Glu Asn
850 855 860
Ser Glu Ile Lys Thr Ser Ile Glu Val Lys Ala Thr Glu Asn Cys Ala
865 870 875 880
Lys Glu Ala Ile Ser Asp Ala Ala Leu Glu Ala Thr Glu Asn Glu Pro
885 890 895
Leu Asn Lys Glu Thr Glu Glu Met Cys Val Met Leu Val Ser Asn Leu
900 905 910
Pro Asn Lys Gly Tyr Ser Val Glu Glu Val Tyr Asp Leu Ala Lys Pro
915 920 925
Phe Gly Gly Leu Lys Asp Ile Leu Ile Leu Ser Ser His Lys Lys Ala
930 935 940
Tyr Ile Glu Ile Asn Arg Lys Ala Ala Glu Ser Met Val Lys Phe Tyr
945 950 955 960
Thr Cys Phe Pro Val Leu Met Asp Gly Asn Gln Leu Ser Ile Ser Met
965 970 975
Ala Pro Glu Asn Met Asn Ile Lys Asp Glu Glu Ala Ile Phe Ile Thr
980 985 990
Leu Val Lys Glu Asn Asp Pro Glu Ala Asn Ile Asp Thr Ile Tyr Asp
995 1000 1005
Arg Phe Val His Leu Asp Asn Leu Pro Glu Asp Gly Leu Gln Cys
1010 1015 1020
Val Leu Cys Val Gly Leu Gln Phe Gly Lys Val Asp His His Val
1025 1030 1035
Phe Ile Ser Asn Arg Asn Lys Ala Ile Leu Gln Leu Asp Ser Pro
1040 1045 1050
Glu Ser Ala Gln Ser Met Tyr Ser Phe Leu Lys Gln Asn Pro Gln
1055 1060 1065
Asn Ile Gly Asp His Met Leu Thr Cys Ser Leu Ser Pro Lys Ile
1070 1075 1080
Asp Leu Pro Glu Val Gln Ile Glu His Asp Pro Glu Leu Glu Lys
1085 1090 1095
Glu Ser Pro Gly Leu Lys Asn Ser Pro Ile Asp Glu Ser Glu Val
1100 1105 1110
Gln Thr Ala Thr Asp Ser Pro Ser Val Lys Pro Asn Glu Leu Glu
1115 1120 1125
Glu Glu Ser Thr Pro Ser Ile Gln Thr Glu Thr Leu Val Gln Gln
1130 1135 1140
Glu Glu Pro Cys Glu Glu Glu Ala Glu Lys Ala Thr Cys Asp Ser
1145 1150 1155
Asp Phe Ala Val Glu Thr Leu Glu Leu Glu Thr Gln Gly Glu Glu
1160 1165 1170
Val Lys Glu Glu Ile Pro Leu Val Ala Ser Ala Ser Val Ser Ile
1175 1180 1185
Glu Gln Phe Thr Glu Asn Ala Glu Glu Cys Ala Leu Asn Gln Gln
1190 1195 1200
Met Phe Asn Ser Asp Leu Glu Lys Lys Gly Ala Glu Ile Ile Asn
1205 1210 1215
Pro Lys Thr Ala Leu Leu Pro Ser Asp Ser Val Phe Ala Glu Glu
1220 1225 1230
Arg Asn Leu Lys Gly Ile Leu Glu Glu Ser Pro Ser Glu Ala Glu
1235 1240 1245
Asp Phe Ile Ser Gly Ile Thr Gln Thr Met Val Glu Ala Val Ala
1250 1255 1260
Glu Val Glu Lys Asn Glu Thr Val Ser Glu Ile Leu Pro Ser Thr
1265 1270 1275
Cys Ile Val Thr Leu Val Pro Gly Ile Pro Thr Gly Asp Glu Lys
1280 1285 1290
Thr Val Asp Lys Lys Asn Ile Ser Glu Lys Lys Gly Asn Met Asp
1295 1300 1305
Glu Lys Glu Glu Lys Glu Phe Asn Thr Lys Glu Thr Arg Met Asp
1310 1315 1320
Leu Gln Ile Gly Thr Glu Lys Ala Glu Lys Asn Glu Gly Arg Met
1325 1330 1335
Asp Ala Glu Lys Val Glu Lys Met Ala Ala Met Lys Glu Lys Pro
1340 1345 1350
Ala Glu Asn Thr Leu Phe Lys Ala Tyr Pro Asn Lys Gly Val Gly
1355 1360 1365
Gln Ala Asn Lys Pro Asp Glu Thr Ser Lys Thr Ser Ile Leu Ala
1370 1375 1380
Val Ser Asp Val Ser Ser Ser Lys Pro Ser Ile Lys Ala Val Ile
1385 1390 1395
Val Ser Ser Pro Lys Ala Lys Ala Thr Val Ser Lys Thr Glu Asn
1400 1405 1410
Gln Lys Ser Phe Pro Lys Ser Val Pro Arg Asp Gln Ile Asn Ala
1415 1420 1425
Glu Lys Lys Leu Ser Ala Lys Glu Phe Gly Leu Leu Lys Pro Thr
1430 1435 1440
Ser Ala Arg Ser Gly Leu Ala Glu Ser Ser Ser Lys Phe Lys Pro
1445 1450 1455
Thr Gln Ser Ser Leu Thr Arg Gly Gly Ser Gly Arg Ile Ser Ala
1460 1465 1470
Leu Gln Gly Lys Leu Ser Lys Leu Asp Tyr Arg Asp Ile Thr Lys
1475 1480 1485
Gln Ser Gln Glu Thr Glu Ala Arg Pro Ser Ile Met Lys Arg Asp
1490 1495 1500
Asp Ser Asn Asn Lys Thr Leu Ala Glu Gln Asn Thr Lys Asn Pro
1505 1510 1515
Lys Ser Thr Thr Gly Arg Ser Ser Lys Ser Lys Glu Glu Pro Leu
1520 1525 1530
Phe Pro Phe Asn Leu Asp Glu Phe Val Thr Val Asp Glu Val Ile
1535 1540 1545
Glu Glu Val Asn Pro Ser Gln Ala Lys Gln Asn Pro Leu Lys Gly
1550 1555 1560
Lys Arg Lys Glu Thr Leu Lys Asn Val Pro Phe Ser Glu Leu Asn
1565 1570 1575
Leu Lys Lys Lys Lys Gly Lys Thr Ser Thr Pro Arg Gly Val Glu
1580 1585 1590
Gly Glu Leu Ser Phe Val Thr Leu Asp Glu Ile Gly Glu Glu Glu
1595 1600 1605
Asp Ala Ala Ala His Leu Ala Gln Ala Leu Val Thr Val Asp Glu
1610 1615 1620
Val Ile Asp Glu Glu Glu Leu Asn Met Glu Glu Met Val Lys Asn
1625 1630 1635
Ser Asn Ser Leu Phe Thr Leu Asp Glu Leu Ile Asp Gln Asp Asp
1640 1645 1650
Cys Ile Ser His Ser Glu Pro Lys Asp Val Thr Val Leu Ser Val
1655 1660 1665
Ala Glu Glu Gln Asp Leu Leu Lys Gln Glu Arg Leu Val Thr Val
1670 1675 1680
Asp Glu Ile Gly Glu Val Glu Glu Leu Pro Leu Asn Glu Ser Ala
1685 1690 1695
Asp Ile Thr Phe Ala Thr Leu Asn Thr Lys Gly Asn Glu Gly Asp
1700 1705 1710
Thr Val Arg Asp Ser Ile Gly Phe Ile Ser Ser Gln Val Pro Glu
1715 1720 1725
Asp Pro Ser Thr Leu Val Thr Val Asp Glu Ile Gln Asp Asp Ser
1730 1735 1740
Ser Asp Leu His Leu Val Thr Leu Asp Glu Val Thr Glu Glu Asp
1745 1750 1755
Glu Asp Ser Leu Ala Asp Phe Asn Asn Leu Lys Glu Glu Leu Asn
1760 1765 1770
Phe Val Thr Val Asp Glu Val Gly Glu Glu Glu Asp Gly Asp Asn
1775 1780 1785
Asp Leu Lys Val Glu Leu Ala Gln Ser Lys Asn Asp His Pro Thr
1790 1795 1800
Asp Lys Lys Gly Asn Arg Lys Lys Arg Ala Val Asp Thr Lys Lys
1805 1810 1815
Thr Lys Leu Glu Ser Leu Ser Gln Val Gly Pro Val Asn Glu Asn
1820 1825 1830
Val Met Glu Glu Asp Leu Lys Thr Met Ile Glu Arg His Leu Thr
1835 1840 1845
Ala Lys Thr Pro Thr Lys Arg Val Arg Ile Gly Lys Thr Leu Pro
1850 1855 1860
Ser Glu Lys Ala Val Val Thr Glu Pro Ala Lys Gly Glu Glu Ala
1865 1870 1875
Phe Gln Met Ser Glu Val Asp Glu Glu Ser Gly Leu Lys Asp Ser
1880 1885 1890
Glu Pro Glu Arg Lys Arg Lys Lys Thr Glu Asp Ser Ser Ser Gly
1895 1900 1905
Lys Ser Val Ala Ser Asp Val Pro Glu Glu Leu Asp Phe Leu Val
1910 1915 1920
Pro Lys Ala Gly Phe Phe Cys Pro Ile Cys Ser Leu Phe Tyr Ser
1925 1930 1935
Gly Glu Lys Ala Met Thr Asn His Cys Lys Ser Thr Arg His Lys
1940 1945 1950
Gln Asn Thr Glu Lys Phe Met Ala Lys Gln Arg Lys Glu Lys Glu
1955 1960 1965
Gln Asn Glu Ala Glu Glu Arg Ser Ser Arg
1970 1975
<210> 208
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> RNA酶1 (R39D, N67D, N88A, G89D, R91D, H119N, K41R, D121E)
<400> 208
Lys Glu Ser Arg Ala Lys Lys Phe Gln Arg Gln His Met Asp Ser Asp
1 5 10 15
Ser Ser Pro Ser Ser Ser Ser Thr Tyr Cys Asn Gln Met Met Arg Arg
20 25 30
Arg Asn Met Thr Gln Gly Asp Cys Arg Pro Val Asn Thr Phe Val His
35 40 45
Glu Pro Leu Val Asp Val Gln Asn Val Cys Phe Gln Glu Lys Val Thr
50 55 60
Cys Lys Asp Gly Gln Gly Asn Cys Tyr Lys Ser Asn Ser Ser Met His
65 70 75 80
Ile Thr Asp Cys Arg Leu Thr Ala Asp Ser Asp Tyr Pro Asn Cys Ala
85 90 95
Tyr Arg Thr Ser Pro Lys Glu Arg His Ile Ile Val Ala Cys Glu Gly
100 105 110
Ser Pro Tyr Val Pro Val Asn Phe Glu Ala Ser Val Glu Asp Ser Thr
115 120 125
<210> 209
<211> 1091
<212> PRT
<213> 未知的
<220>
<223> PUMBY
<400> 209
Met Asp Lys Ser Lys Gln Met Asn Ile Asn Asn Leu Ser Asn Ile Pro
1 5 10 15
Glu Val Ile Asp Pro Gly Ile Thr Ile Pro Ile Tyr Glu Glu Glu Tyr
20 25 30
Glu Asn Asn Gly Glu Ser Asn Ser Gln Leu Gln Gln Gln Pro Gln Lys
35 40 45
Leu Gly Ser Tyr Arg Ser Arg Ala Gly Lys Phe Ser Asn Thr Leu Ser
50 55 60
Asn Leu Leu Pro Ser Ile Ser Ala Lys Leu His His Ser Lys Lys Asn
65 70 75 80
Ser His Gly Lys Asn Gly Ala Glu Phe Ser Ser Ser Asn Asn Ser Ser
85 90 95
Gln Ser Thr Val Ala Ser Lys Thr Pro Arg Ala Ser Pro Ser Arg Ser
100 105 110
Lys Met Met Glu Ser Ser Ile Asp Gly Val Thr Met Asp Arg Pro Gly
115 120 125
Ser Leu Thr Pro Pro Gln Asp Met Glu Lys Leu Val His Phe Pro Asp
130 135 140
Ser Ser Asn Asn Phe Leu Ile Pro Ala Pro Arg Gly Ser Ser Asp Ser
145 150 155 160
Phe Asn Leu Pro His Gln Ile Ser Arg Thr Arg Asn Asn Thr Met Ser
165 170 175
Ser Gln Ile Thr Ser Ile Ser Ser Ile Ala Pro Lys Pro Arg Thr Ser
180 185 190
Ser Gly Ile Trp Ser Ser Asn Ala Ser Ala Asn Asp Pro Met Gln Gln
195 200 205
His Leu Leu Gln Gln Leu Gln Pro Thr Thr Ser Asn Asn Thr Thr Asn
210 215 220
Ser Asn Thr Leu Asn Asp Tyr Ser Thr Lys Thr Ala Tyr Phe Asp Asn
225 230 235 240
Met Val Ser Thr Ser Gly Ser Gln Met Ala Asp Asn Lys Met Asn Thr
245 250 255
Asn Asn Leu Ala Ile Pro Asn Ser Val Trp Ser Asn Thr Arg Gln Arg
260 265 270
Ser Gln Ser Asn Ala Ser Ser Ile Tyr Thr Asp Ala Pro Leu Tyr Glu
275 280 285
Gln Pro Ala Arg Ala Ser Ile Ser Ser His Tyr Thr Ile Pro Thr Gln
290 295 300
Glu Ser Pro Leu Ile Ala Asp Glu Ile Asp Pro Gln Ser Ile Asn Trp
305 310 315 320
Val Thr Met Asp Pro Thr Val Pro Ser Ile Asn Gln Ile Ser Asn Leu
325 330 335
Leu Pro Thr Asn Thr Ile Ser Ile Ser Asn Val Phe Pro Leu Gln His
340 345 350
Gln Gln Pro Gln Leu Asn Asn Ala Ile Asn Leu Thr Ser Thr Ser Leu
355 360 365
Ala Thr Leu Cys Ser Lys Tyr Gly Glu Val Ile Ser Ala Arg Thr Leu
370 375 380
Arg Asn Leu Asn Met Ala Leu Val Glu Phe Ser Ser Val Glu Ser Ala
385 390 395 400
Val Lys Ala Leu Asp Ser Leu Gln Gly Lys Glu Val Ser Met Ile Gly
405 410 415
Ala Pro Ser Lys Ile Ser Phe Ala Lys Ile Leu Pro Met His Gln Gln
420 425 430
Pro Pro Gln Phe Leu Leu Asn Ser Gln Gly Leu Pro Leu Gly Leu Glu
435 440 445
Asn Asn Asn Leu Gln Pro Gln Pro Leu Leu Gln Glu Gln Leu Phe Asn
450 455 460
Gly Ala Val Thr Phe Gln Gln Gln Gly Asn Val Ser Ile Pro Val Phe
465 470 475 480
Asn Gln Gln Ser Gln Gln Ser Gln His Gln Asn His Ser Ser Gly Ser
485 490 495
Ala Gly Phe Ser Asn Val Leu His Gly Tyr Asn Asn Asn Asn Ser Met
500 505 510
His Gly Asn Asn Asn Asn Ser Ala Asn Glu Lys Glu Gln Cys Pro Phe
515 520 525
Pro Leu Pro Pro Pro Asn Val Asn Glu Lys Glu Asp Leu Leu Arg Glu
530 535 540
Ile Ile Glu Leu Phe Glu Ala Asn Ser Asp Glu Tyr Gln Ile Asn Ser
545 550 555 560
Leu Ile Lys Lys Ser Leu Asn His Lys Gly Thr Ser Asp Thr Gln Asn
565 570 575
Phe Gly Pro Leu Pro Glu Pro Leu Ser Gly Arg Glu Phe Asp Pro Pro
580 585 590
Lys Leu Arg Glu Leu Arg Lys Ser Ile Asp Ser Asn Ala Phe Ser Asp
595 600 605
Leu Glu Ile Glu Gln Leu Ala Ile Ala Met Leu Asp Glu Leu Pro Glu
610 615 620
Leu Ser Ser Asp Tyr Leu Gly Asn Thr Ile Val Gln Lys Leu Phe Glu
625 630 635 640
His Ser Ser Asp Ile Ile Lys Asp Ile Met Leu Arg Lys Thr Ser Lys
645 650 655
Tyr Leu Thr Ser Met Gly Val His Lys Asn Gly Thr Trp Ala Cys Gln
660 665 670
Lys Met Ile Thr Met Ala His Thr Pro Arg Gln Ile Met Gln Val Thr
675 680 685
Gln Gly Val Lys Asp Tyr Cys Thr Pro Leu Ile Asn Asp Gln Phe Gly
690 695 700
Asn Tyr Val Ile Gln Cys Val Leu Lys Phe Gly Phe Pro Trp Asn Gln
705 710 715 720
Phe Ile Phe Glu Ser Ile Ile Ala Asn Phe Trp Val Ile Val Gln Asn
725 730 735
Arg Tyr Gly Ala Arg Ala Val Arg Ala Cys Leu Glu Ala His Asp Ile
740 745 750
Val Thr Pro Glu Gln Ser Ile Val Leu Ser Ala Met Ile Val Thr Tyr
755 760 765
Ala Glu Tyr Leu Ser Thr Asn Ser Asn Gly Ala Leu Leu Val Thr Trp
770 775 780
Phe Leu Asp Thr Ser Val Leu Pro Asn Arg His Ser Ile Leu Ala Pro
785 790 795 800
Arg Leu Thr Lys Arg Ile Val Glu Leu Cys Gly His Arg Leu Ala Ser
805 810 815
Leu Thr Ile Leu Lys Val Leu Asn Tyr Arg Gly Asp Asp Asn Ala Arg
820 825 830
Lys Ile Ile Leu Asp Ser Leu Phe Gly Asn Val Asn Ala His Asp Ser
835 840 845
Ser Pro Pro Lys Glu Leu Thr Lys Leu Leu Cys Glu Thr Asn Tyr Gly
850 855 860
Pro Thr Phe Val His Lys Val Leu Ala Met Pro Leu Leu Glu Asp Asp
865 870 875 880
Leu Arg Ala His Ile Ile Lys Gln Val Arg Lys Val Leu Thr Asp Ser
885 890 895
Thr Gln Ile Gln Pro Ser Arg Arg Leu Leu Glu Glu Val Gly Leu Ala
900 905 910
Ser Pro Ser Ser Thr His Asn Lys Thr Lys Gln Gln Gln Gln Gln His
915 920 925
His Asn Ser Ser Ile Ser His Met Phe Ala Thr Pro Asp Thr Ser Gly
930 935 940
Gln His Met Arg Gly Leu Ser Val Ser Ser Val Lys Ser Gly Gly Ser
945 950 955 960
Lys His Thr Thr Met Asn Thr Thr Thr Thr Asn Gly Ser Ser Ala Ser
965 970 975
Thr Leu Ser Pro Gly Gln Pro Leu Asn Ala Asn Ser Asn Ser Ser Met
980 985 990
Gly Tyr Phe Ser Tyr Pro Gly Val Phe Pro Val Ser Gly Phe Ser Gly
995 1000 1005
Asn Ala Ser Asn Gly Tyr Ala Met Asn Asn Asp Asp Leu Ser Ser
1010 1015 1020
Gln Phe Asp Met Leu Asn Phe Asn Asn Gly Thr Arg Leu Ser Leu
1025 1030 1035
Pro Gln Leu Ser Leu Thr Asn His Asn Asn Thr Thr Met Glu Leu
1040 1045 1050
Val Asn Asn Val Gly Ser Ser Gln Pro His Thr Asn Asn Asn Asn
1055 1060 1065
Asn Asn Asn Asn Thr Asn Tyr Asn Asp Asp Asn Thr Val Phe Glu
1070 1075 1080
Thr Leu Thr Leu His Ser Ala Asn
1085 1090
<210> 210
<211> 879
<212> PRT
<213> 未知的
<220>
<223> PUF3
<400> 210
Met Glu Met Asn Met Asp Met Asp Met Asp Met Glu Leu Ala Ser Ile
1 5 10 15
Val Ser Ser Leu Ser Ala Leu Ser His Ser Asn Asn Asn Gly Gly Gln
20 25 30
Ala Ala Ala Ala Gly Ile Val Asn Gly Gly Ala Ala Gly Ser Gln Gln
35 40 45
Ile Gly Gly Phe Arg Arg Ser Ser Phe Thr Thr Ala Asn Glu Val Asp
50 55 60
Ser Glu Ile Leu Leu Leu His Gly Ser Ser Glu Ser Ser Pro Ile Phe
65 70 75 80
Lys Lys Thr Ala Leu Ser Val Gly Thr Ala Pro Pro Phe Ser Thr Asn
85 90 95
Ser Lys Lys Phe Phe Gly Asn Gly Gly Asn Tyr Tyr Gln Tyr Arg Ser
100 105 110
Thr Asp Thr Ala Ser Leu Ser Ser Ala Ser Tyr Asn Asn Tyr His Thr
115 120 125
His His Thr Ala Ala Asn Leu Gly Lys Asn Asn Lys Val Asn His Leu
130 135 140
Leu Gly Gln Tyr Ser Ala Ser Ile Ala Gly Pro Val Tyr Tyr Asn Gly
145 150 155 160
Asn Asp Asn Asn Asn Ser Gly Gly Glu Gly Phe Phe Glu Lys Phe Gly
165 170 175
Lys Ser Leu Ile Asp Gly Thr Arg Glu Leu Glu Ser Gln Asp Arg Pro
180 185 190
Asp Ala Val Asn Thr Gln Ser Gln Phe Ile Ser Lys Ser Val Ser Asn
195 200 205
Ala Ser Leu Asp Thr Gln Asn Thr Phe Glu Gln Asn Val Glu Ser Asp
210 215 220
Lys Asn Phe Asn Lys Leu Asn Arg Asn Thr Thr Asn Ser Gly Ser Leu
225 230 235 240
Tyr His Ser Ser Ser Asn Ser Gly Ser Ser Ala Ser Leu Glu Ser Glu
245 250 255
Asn Ala His Tyr Pro Lys Arg Asn Ile Trp Asn Val Ala Asn Thr Pro
260 265 270
Val Phe Arg Pro Ser Asn Asn Pro Ala Ala Val Gly Ala Thr Asn Val
275 280 285
Ala Leu Pro Asn Gln Gln Asp Gly Pro Ala Asn Asn Asn Phe Pro Pro
290 295 300
Tyr Met Asn Gly Phe Pro Pro Asn Gln Phe His Gln Gly Pro His Tyr
305 310 315 320
Gln Asn Phe Pro Asn Tyr Leu Ile Gly Ser Pro Ser Asn Phe Ile Ser
325 330 335
Gln Met Ile Ser Val Gln Ile Pro Ala Asn Glu Asp Thr Glu Asp Ser
340 345 350
Asn Gly Lys Lys Lys Lys Lys Ala Asn Arg Pro Ser Ser Val Ser Ser
355 360 365
Pro Ser Ser Pro Pro Asn Asn Ser Pro Phe Pro Phe Ala Tyr Pro Asn
370 375 380
Pro Met Met Phe Met Pro Pro Pro Pro Leu Ser Ala Pro Gln Gln Gln
385 390 395 400
Gln Gln Gln Gln Gln Gln Gln Gln Gln Glu Asp Gln Gln Gln Gln Gln
405 410 415
Gln Gln Glu Asn Pro Tyr Ile Tyr Tyr Pro Thr Pro Asn Pro Ile Pro
420 425 430
Val Lys Met Pro Lys Asp Glu Lys Thr Phe Lys Lys Arg Asn Asn Lys
435 440 445
Asn His Pro Ala Asn Asn Ser Asn Asn Ala Asn Lys Gln Ala Asn Pro
450 455 460
Tyr Leu Glu Asn Ser Ile Pro Thr Lys Asn Thr Ser Lys Lys Asn Ala
465 470 475 480
Ser Ser Lys Ser Asn Glu Ser Thr Ala Asn Asn His Lys Ser His Ser
485 490 495
His Ser His Pro His Ser Gln Ser Leu Gln Gln Gln Gln Gln Thr Tyr
500 505 510
His Arg Ser Pro Leu Leu Glu Gln Leu Arg Asn Ser Ser Ser Asp Lys
515 520 525
Asn Ser Asn Ser Asn Met Ser Leu Lys Asp Ile Phe Gly His Ser Leu
530 535 540
Glu Phe Cys Lys Asp Gln His Gly Ser Arg Phe Ile Gln Arg Glu Leu
545 550 555 560
Ala Thr Ser Pro Ala Ser Glu Lys Glu Val Ile Phe Asn Glu Ile Arg
565 570 575
Asp Asp Ala Ile Glu Leu Ser Asn Asp Val Phe Gly Asn Tyr Val Ile
580 585 590
Gln Lys Phe Phe Glu Phe Gly Ser Lys Ile Gln Lys Asn Thr Leu Val
595 600 605
Asp Gln Phe Lys Gly Asn Met Lys Gln Leu Ser Leu Gln Met Tyr Ala
610 615 620
Cys Arg Val Ile Gln Lys Ala Leu Glu Tyr Ile Asp Ser Asn Gln Arg
625 630 635 640
Ile Glu Leu Val Leu Glu Leu Ser Asp Ser Val Leu Gln Met Ile Lys
645 650 655
Asp Gln Asn Gly Asn His Val Ile Gln Lys Ala Ile Glu Thr Ile Pro
660 665 670
Ile Glu Lys Leu Pro Phe Ile Leu Ser Ser Leu Thr Gly His Ile Tyr
675 680 685
His Leu Ser Thr His Ser Tyr Gly Cys Arg Val Ile Gln Arg Leu Leu
690 695 700
Glu Phe Gly Ser Ser Glu Asp Gln Glu Ser Ile Leu Asn Glu Leu Lys
705 710 715 720
Asp Phe Ile Pro Tyr Leu Ile Gln Asp Gln Tyr Gly Asn Tyr Val Ile
725 730 735
Gln Tyr Val Leu Gln Gln Asp Gln Phe Thr Asn Lys Glu Met Val Asp
740 745 750
Ile Lys Gln Glu Ile Ile Glu Thr Val Ala Asn Asn Val Val Glu Tyr
755 760 765
Ser Lys His Lys Phe Ala Ser Asn Val Val Glu Lys Ser Ile Leu Tyr
770 775 780
Gly Ser Lys Asn Gln Lys Asp Leu Ile Ile Ser Lys Ile Leu Pro Arg
785 790 795 800
Asp Lys Asn His Ala Leu Asn Leu Glu Asp Asp Ser Pro Met Ile Leu
805 810 815
Met Ile Lys Asp Gln Phe Ala Asn Tyr Val Ile Gln Lys Leu Val Asn
820 825 830
Val Ser Glu Gly Glu Gly Lys Lys Leu Ile Val Ile Ala Ile Arg Ala
835 840 845
Tyr Leu Asp Lys Leu Asn Lys Ser Asn Ser Leu Gly Asn Arg His Leu
850 855 860
Ala Ser Val Glu Lys Leu Ala Ala Leu Val Glu Asn Ala Glu Val
865 870 875
<210> 211
<211> 888
<212> PRT
<213> 未知的
<220>
<223> PUF4
<400> 211
Met Ser Thr Lys Gly Leu Lys Glu Glu Ile Asp Asp Val Pro Ser Val
1 5 10 15
Asp Pro Val Val Ser Glu Thr Val Asn Ser Ala Leu Glu Gln Leu Gln
20 25 30
Leu Asp Asp Pro Glu Glu Asn Ala Thr Ser Asn Ala Phe Ala Asn Lys
35 40 45
Val Ser Gln Asp Ser Gln Phe Ala Asn Gly Pro Pro Ser Gln Met Phe
50 55 60
Pro His Pro Gln Met Met Gly Gly Met Gly Phe Met Pro Tyr Ser Gln
65 70 75 80
Met Met Gln Val Pro His Asn Pro Cys Pro Phe Phe Pro Pro Pro Asp
85 90 95
Phe Asn Asp Pro Thr Ala Pro Leu Ser Ser Ser Pro Leu Asn Ala Gly
100 105 110
Gly Pro Pro Met Leu Phe Lys Asn Asp Ser Leu Pro Phe Gln Met Leu
115 120 125
Ser Ser Gly Ala Ala Val Ala Thr Gln Gly Gly Gln Asn Leu Asn Pro
130 135 140
Leu Ile Asn Asp Asn Ser Met Lys Val Leu Pro Ile Ala Ser Ala Asp
145 150 155 160
Pro Leu Trp Thr His Ser Asn Val Pro Gly Ser Ala Ser Val Ala Ile
165 170 175
Glu Glu Thr Thr Ala Thr Leu Gln Glu Ser Leu Pro Ser Lys Gly Arg
180 185 190
Glu Ser Asn Asn Lys Ala Ser Ser Phe Arg Arg Gln Thr Phe His Ala
195 200 205
Leu Ser Pro Thr Asp Leu Ile Asn Ala Ala Asn Asn Val Thr Leu Ser
210 215 220
Lys Asp Phe Gln Ser Asp Met Gln Asn Phe Ser Lys Ala Lys Lys Pro
225 230 235 240
Ser Val Gly Ala Asn Asn Thr Ala Lys Thr Arg Thr Gln Ser Ile Ser
245 250 255
Phe Asp Asn Thr Pro Ser Ser Thr Ser Phe Ile Pro Pro Thr Asn Ser
260 265 270
Val Ser Glu Lys Leu Ser Asp Phe Lys Ile Glu Thr Ser Lys Glu Asp
275 280 285
Leu Ile Asn Lys Thr Ala Pro Ala Lys Lys Glu Ser Pro Thr Thr Tyr
290 295 300
Gly Ala Ala Tyr Pro Tyr Gly Gly Pro Leu Leu Gln Pro Asn Pro Ile
305 310 315 320
Met Pro Gly His Pro His Asn Ile Ser Ser Pro Ile Tyr Gly Ile Arg
325 330 335
Ser Pro Phe Pro Asn Ser Tyr Glu Met Gly Ala Gln Phe Gln Pro Phe
340 345 350
Ser Pro Ile Leu Asn Pro Thr Ser His Ser Leu Asn Ala Asn Ser Pro
355 360 365
Ile Pro Leu Thr Gln Ser Pro Ile His Leu Ala Pro Val Leu Asn Pro
370 375 380
Ser Ser Asn Ser Val Ala Phe Ser Asp Met Lys Asn Asp Gly Gly Lys
385 390 395 400
Pro Thr Thr Asp Asn Asp Lys Ala Gly Pro Asn Val Arg Met Asp Leu
405 410 415
Ile Asn Pro Asn Leu Gly Pro Ser Met Gln Pro Phe His Ile Leu Pro
420 425 430
Pro Gln Gln Asn Thr Pro Pro Pro Pro Trp Leu Tyr Ser Thr Pro Pro
435 440 445
Pro Phe Asn Ala Met Val Pro Pro His Leu Leu Ala Gln Asn His Met
450 455 460
Pro Leu Met Asn Ser Ala Asn Asn Lys His His Gly Arg Asn Asn Asn
465 470 475 480
Ser Met Ser Ser His Asn Asp Asn Asp Asn Ile Gly Asn Ser Asn Tyr
485 490 495
Asn Asn Lys Asp Thr Gly Arg Ser Asn Val Gly Lys Met Lys Asn Met
500 505 510
Lys Asn Ser Tyr His Gly Tyr Tyr Asn Asn Asn Asn Asn Asn Asn Asn
515 520 525
Asn Asn Asn Asn Asn Asn Asn Ser Asn Ala Thr Asn Ser Asn Ser Ala
530 535 540
Glu Lys Gln Arg Lys Ile Glu Glu Ser Ser Arg Phe Ala Asp Ala Val
545 550 555 560
Leu Asp Gln Tyr Ile Gly Ser Ile His Ser Leu Cys Lys Asp Gln His
565 570 575
Gly Cys Arg Phe Leu Gln Lys Gln Leu Asp Ile Leu Gly Ser Lys Ala
580 585 590
Ala Asp Ala Ile Phe Glu Glu Thr Lys Asp Tyr Thr Val Glu Leu Met
595 600 605
Thr Asp Ser Phe Gly Asn Tyr Leu Ile Gln Lys Leu Leu Glu Glu Val
610 615 620
Thr Thr Glu Gln Arg Ile Val Leu Thr Lys Ile Ser Ser Pro His Phe
625 630 635 640
Val Glu Ile Ser Leu Asn Pro His Gly Thr Arg Ala Leu Gln Lys Leu
645 650 655
Ile Glu Cys Ile Lys Thr Asp Glu Glu Ala Gln Ile Val Val Asp Ser
660 665 670
Leu Arg Pro Tyr Thr Val Gln Leu Ser Lys Asp Leu Asn Gly Asn His
675 680 685
Val Ile Gln Lys Cys Leu Gln Arg Leu Lys Pro Glu Asn Phe Gln Phe
690 695 700
Ile Phe Asp Ala Ile Ser Asp Ser Cys Ile Asp Ile Ala Thr His Arg
705 710 715 720
His Gly Cys Cys Val Leu Gln Arg Cys Leu Asp His Gly Thr Thr Glu
725 730 735
Gln Cys Asp Asn Leu Cys Asp Lys Leu Leu Ala Leu Val Asp Lys Leu
740 745 750
Thr Leu Asp Pro Phe Gly Asn Tyr Val Val Gln Tyr Ile Ile Thr Lys
755 760 765
Glu Ala Glu Lys Asn Lys Tyr Asp Tyr Thr His Lys Ile Val His Leu
770 775 780
Leu Lys Pro Arg Ala Ile Glu Leu Ser Ile His Lys Phe Gly Ser Asn
785 790 795 800
Val Ile Glu Lys Ile Leu Lys Thr Ala Ile Val Ser Glu Pro Met Ile
805 810 815
Leu Glu Ile Leu Asn Asn Gly Gly Glu Thr Gly Ile Gln Ser Leu Leu
820 825 830
Asn Asp Ser Tyr Gly Asn Tyr Val Leu Gln Thr Ala Leu Asp Ile Ser
835 840 845
His Lys Gln Asn Asp Tyr Leu Tyr Lys Arg Leu Ser Glu Ile Val Ala
850 855 860
Pro Leu Leu Val Gly Pro Ile Arg Asn Thr Pro His Gly Lys Arg Ile
865 870 875 880
Ile Gly Met Leu His Leu Asp Ser
885
<210> 212
<211> 553
<212> PRT
<213> 未知的
<220>
<223> PUF5
<400> 212
Met Ser Asp Ser Thr Gly Arg Ile Asn Ser Lys Ala Ser Asp Ser Ser
1 5 10 15
Ser Ile Ser Asp His Gln Thr Ala Asp Leu Ser Ile Phe Asn Gly Ser
20 25 30
Phe Asp Gly Gly Ala Phe Ser Ser Ser Asn Ile Pro Leu Phe Asn Phe
35 40 45
Met Gly Thr Gly Asn Gln Arg Phe Gln Tyr Ser Pro His Pro Phe Ala
50 55 60
Lys Ser Ser Asp Pro Cys Arg Leu Ala Ala Leu Thr Pro Ser Thr Pro
65 70 75 80
Lys Gly Pro Leu Asn Leu Thr Pro Ala Asp Phe Gly Leu Ala Asp Phe
85 90 95
Ser Val Gly Asn Glu Ser Phe Ala Asp Phe Thr Ala Asn Asn Thr Ser
100 105 110
Phe Val Gly Asn Val Gln Ser Asn Val Arg Ser Thr Arg Leu Leu Pro
115 120 125
Ala Trp Ala Val Asp Asn Ser Gly Asn Ile Arg Asp Asp Leu Thr Leu
130 135 140
Gln Asp Val Val Ser Asn Gly Ser Leu Ile Asp Phe Ala Met Asp Arg
145 150 155 160
Thr Gly Val Lys Phe Leu Glu Arg His Phe Pro Glu Asp His Asp Asn
165 170 175
Glu Met His Phe Val Leu Phe Asp Lys Leu Thr Glu Gln Gly Ala Val
180 185 190
Phe Thr Ser Leu Cys Arg Ser Ala Ala Gly Asn Phe Ile Ile Gln Lys
195 200 205
Phe Val Glu His Ala Thr Leu Asp Glu Gln Glu Arg Leu Val Arg Lys
210 215 220
Met Cys Asp Asn Gly Leu Ile Glu Met Cys Leu Asp Lys Phe Ala Cys
225 230 235 240
Arg Val Val Gln Met Ser Ile Gln Lys Phe Asp Val Ser Ile Ala Met
245 250 255
Lys Leu Val Glu Lys Ile Ser Ser Leu Asp Phe Leu Pro Leu Cys Thr
260 265 270
Asp Gln Cys Ala Ile His Val Leu Gln Lys Val Val Lys Leu Leu Pro
275 280 285
Ile Ser Ala Trp Ser Phe Phe Val Lys Phe Leu Cys Arg Asp Asp Asn
290 295 300
Leu Met Thr Val Cys Gln Asp Lys Tyr Gly Cys Arg Leu Val Gln Gln
305 310 315 320
Thr Ile Asp Lys Leu Ser Asp Asn Pro Lys Leu His Cys Phe Asn Thr
325 330 335
Arg Leu Gln Leu Leu His Gly Leu Met Thr Ser Val Ala Arg Asn Cys
340 345 350
Phe Arg Leu Ser Ser Asn Glu Phe Ala Asn Tyr Val Val Gln Tyr Val
355 360 365
Ile Lys Ser Ser Gly Val Met Glu Met Tyr Arg Asp Thr Ile Ile Glu
370 375 380
Lys Cys Leu Leu Arg Asn Ile Leu Ser Met Ser Gln Asp Lys Tyr Ala
385 390 395 400
Ser His Val Val Glu Gly Ala Phe Leu Phe Ala Pro Pro Leu Leu Leu
405 410 415
Ser Glu Met Met Asp Glu Ile Phe Asp Gly Tyr Val Lys Asp Gln Glu
420 425 430
Thr Asn Arg Asp Ala Leu Asp Ile Leu Leu Phe His Gln Tyr Gly Asn
435 440 445
Tyr Val Val Gln Gln Met Ile Ser Ile Cys Ile Ser Ala Leu Leu Gly
450 455 460
Lys Glu Glu Arg Lys Met Val Ala Ser Glu Met Arg Leu Tyr Ala Lys
465 470 475 480
Trp Phe Asp Arg Ile Lys Asn Arg Val Asn Arg His Ser Gly Arg Leu
485 490 495
Glu Arg Phe Ser Ser Gly Lys Lys Ile Ile Glu Ser Leu Gln Lys Leu
500 505 510
Asn Val Pro Met Thr Met Thr Asn Glu Pro Met Pro Tyr Trp Ala Met
515 520 525
Pro Thr Pro Leu Met Asp Ile Ser Ala His Phe Met Asn Lys Leu Asn
530 535 540
Phe Gln Lys Asn Ser Val Phe Asp Glu
545 550
<210> 213
<211> 485
<212> PRT
<213> 未知的
<220>
<223> PUF6
<400> 213
Met Thr Pro Asn Arg Arg Ser Thr Asp Ser Tyr Asn Met Leu Gly Ala
1 5 10 15
Ser Phe Asp Phe Asp Pro Asp Phe Ser Leu Leu Ser Asn Lys Thr His
20 25 30
Lys Asn Lys Asn Pro Lys Pro Pro Val Lys Leu Leu Pro Tyr Arg His
35 40 45
Gly Ser Asn Thr Thr Ser Ser Asp Leu Asp Asn Tyr Ile Phe Asn Ser
50 55 60
Gly Ser Gly Ser Ser Asp Asp Glu Thr Pro Pro Pro Ala Ala Pro Ile
65 70 75 80
Phe Ile Ser Leu Glu Glu Val Leu Leu Asn Gly Leu Leu Ile Asp Phe
85 90 95
Ala Ile Asp Pro Ser Gly Val Lys Phe Leu Glu Ala Asn Tyr Pro Leu
100 105 110
Asp Ser Glu Asp Gln Ile Arg Lys Ala Val Phe Glu Lys Leu Thr Glu
115 120 125
Ser Thr Thr Leu Phe Val Gly Leu Cys His Ser Arg Asn Gly Asn Phe
130 135 140
Ile Val Gln Lys Leu Val Glu Leu Ala Thr Pro Ala Glu Gln Arg Glu
145 150 155 160
Leu Leu Arg Gln Met Ile Asp Gly Gly Leu Leu Val Met Cys Lys Asp
165 170 175
Lys Phe Ala Cys Arg Val Val Gln Leu Ala Leu Gln Lys Phe Asp His
180 185 190
Ser Asn Val Phe Gln Leu Ile Gln Glu Leu Ser Thr Phe Asp Leu Ala
195 200 205
Ala Met Cys Thr Asp Gln Ile Ser Ile His Val Ile Gln Arg Val Val
210 215 220
Lys Gln Leu Pro Val Asp Met Trp Thr Phe Phe Val His Phe Leu Ser
225 230 235 240
Ser Gly Asp Ser Leu Met Ala Val Cys Gln Asp Lys Tyr Gly Cys Arg
245 250 255
Leu Val Gln Gln Val Ile Asp Arg Leu Ala Glu Asn Pro Lys Leu Pro
260 265 270
Cys Phe Lys Phe Arg Ile Gln Leu Leu His Ser Leu Met Thr Cys Ile
275 280 285
Val Arg Asn Cys Tyr Arg Leu Ser Ser Asn Glu Phe Ala Asn Tyr Val
290 295 300
Ile Gln Tyr Val Ile Lys Ser Ser Gly Ile Met Glu Met Tyr Arg Asp
305 310 315 320
Thr Ile Ile Asp Lys Cys Leu Leu Arg Asn Leu Leu Ser Met Ser Gln
325 330 335
Asp Lys Tyr Ala Ser His Val Ile Glu Gly Ala Phe Leu Phe Ala Pro
340 345 350
Pro Ala Leu Leu His Glu Met Met Glu Glu Ile Phe Ser Gly Tyr Val
355 360 365
Lys Asp Val Glu Leu Asn Arg Asp Ala Leu Asp Ile Leu Leu Phe His
370 375 380
Gln Tyr Gly Asn Tyr Val Val Gln Gln Met Ile Ser Ile Cys Thr Ala
385 390 395 400
Ala Leu Ile Gly Lys Glu Glu Arg Gln Leu Pro Pro Ala Ile Leu Leu
405 410 415
Leu Tyr Ser Gly Trp Tyr Glu Lys Met Lys Gln Arg Val Leu Gln His
420 425 430
Ala Ser Arg Leu Glu Arg Phe Ser Ser Gly Lys Lys Ile Ile Asp Ser
435 440 445
Val Met Arg His Gly Val Pro Thr Ala Ala Ala Ile Asn Ala Gln Ala
450 455 460
Ala Pro Ser Leu Met Glu Leu Thr Ala Gln Phe Asp Ala Met Phe Pro
465 470 475 480
Ser Phe Leu Ala Arg
485
<210> 214
<211> 485
<212> PRT
<213> 未知的
<220>
<223> PUF7
<400> 214
Met Thr Pro Asn Arg Arg Ser Thr Asp Ser Tyr Asn Met Leu Gly Ala
1 5 10 15
Ser Phe Asp Phe Asp Pro Asp Phe Ser Leu Leu Ser Asn Lys Thr His
20 25 30
Lys Asn Lys Asn Pro Lys Pro Pro Val Lys Leu Leu Pro Tyr Arg His
35 40 45
Gly Ser Asn Thr Thr Ser Ser Asp Ser Asp Ser Tyr Ile Phe Asn Ser
50 55 60
Gly Ser Gly Ser Ser Asp Ala Glu Thr Pro Ala Pro Val Ala Pro Ile
65 70 75 80
Phe Ile Ser Leu Glu Asp Val Leu Leu Asn Gly Gln Leu Ile Asp Phe
85 90 95
Ala Ile Asp Pro Ser Gly Val Lys Phe Leu Glu Ala Asn Tyr Pro Leu
100 105 110
Asp Ser Glu Asp Gln Ile Arg Lys Ala Val Phe Glu Lys Phe Thr Glu
115 120 125
Ser Thr Thr Leu Phe Val Gly Leu Cys His Ser Arg Asn Gly Asn Phe
130 135 140
Ile Val Gln Lys Leu Val Glu Leu Ala Thr Pro Ala Glu Gln Arg Glu
145 150 155 160
Leu Leu Arg Gln Met Ile Asp Gly Gly Leu Leu Ala Met Cys Lys Asp
165 170 175
Lys Phe Ala Cys Arg Val Val Gln Leu Ala Leu Gln Lys Phe Asp His
180 185 190
Ser Asn Val Phe Gln Leu Ile Gln Glu Leu Ser Thr Phe Asp Leu Ala
195 200 205
Ala Met Cys Thr Asp Gln Ile Ser Ile His Val Ile Gln Arg Val Val
210 215 220
Lys Gln Leu Pro Val Asp Met Trp Thr Phe Phe Val His Phe Leu Ser
225 230 235 240
Ser Gly Asp Ser Leu Met Ala Val Cys Gln Asp Lys Tyr Gly Cys Arg
245 250 255
Leu Val Gln Gln Val Ile Asp Arg Leu Ala Glu Asn Pro Lys Leu Pro
260 265 270
Cys Phe Lys Phe Arg Ile Gln Leu Leu His Ser Leu Met Thr Cys Ile
275 280 285
Val Arg Asn Cys Tyr Arg Leu Ser Ser Asn Glu Phe Ala Asn Tyr Val
290 295 300
Ile Gln Tyr Val Ile Lys Ser Ser Gly Ile Met Glu Met Tyr Arg Asp
305 310 315 320
Thr Ile Ile Asp Lys Cys Leu Leu Arg Asn Leu Leu Ser Met Ser Gln
325 330 335
Asp Lys Tyr Ala Ser His Val Ile Glu Gly Ala Phe Leu Phe Ala Pro
340 345 350
Pro Ala Leu Leu His Glu Met Met Glu Glu Ile Phe Ser Gly Tyr Val
355 360 365
Lys Asp Val Glu Ser Asn Arg Asp Ala Leu Asp Ile Leu Leu Phe His
370 375 380
Gln Tyr Gly Asn Tyr Val Val Gln Gln Met Ile Ser Ile Cys Thr Ala
385 390 395 400
Ala Leu Ile Gly Lys Glu Glu Arg Glu Leu Pro Pro Ala Ile Leu Leu
405 410 415
Leu Tyr Ser Gly Trp Tyr Glu Lys Met Lys Gln Arg Val Leu Gln His
420 425 430
Ala Ser Arg Leu Glu Arg Phe Ser Ser Gly Lys Lys Ile Ile Asp Ser
435 440 445
Val Met Arg His Gly Val Pro Thr Ala Ala Ala Val Asn Ala Gln Ala
450 455 460
Ala Pro Ser Leu Met Glu Leu Thr Ala Gln Phe Asp Ala Met Phe Pro
465 470 475 480
Ser Phe Leu Ala Arg
485
<210> 215
<211> 535
<212> PRT
<213> 未知的
<220>
<223> PUF8
<400> 215
Met Ser Arg Pro Ile Ser Ile Gly Asn Thr Cys Thr Phe Asp Pro Ser
1 5 10 15
Ala Ser Pro Ile Glu Ser Leu Gly Arg Ser Ile Gly Ala Gln Lys Ile
20 25 30
Val Asp Ser Val Cys Gly Ser Pro Ile Arg Ser Tyr Gly Arg His Ile
35 40 45
Ser Thr Asn Pro Lys Asn Glu Arg Leu Pro Asp Thr Pro Glu Phe Gln
50 55 60
Phe Ala Thr Tyr Met His Gln Gly Gly Lys Val Ile Gly Gln Asn Thr
65 70 75 80
Leu His Met Phe Gly Thr Pro Pro Ser Cys Tyr Cys Ala Gln Glu Asn
85 90 95
Ile Pro Ile Ser Ser Asn Val Gly His Val Leu Ser Thr Ile Asn Asn
100 105 110
Asn Tyr Met Asn His Gln Tyr Asn Gly Ser Asn Met Phe Ser Asn Gln
115 120 125
Met Thr Gln Met Leu Gln Ala Gln Ala Tyr Asn Asp Leu Gln Met His
130 135 140
Gln Ala His Ser Gln Ser Ile Arg Val Pro Val Gln Pro Ser Ala Thr
145 150 155 160
Gly Ile Phe Ser Asn Pro Tyr Arg Glu Pro Thr Thr Thr Asp Asp Leu
165 170 175
Leu Thr Arg Tyr Arg Ala Asn Pro Ala Met Met Lys Asn Leu Lys Leu
180 185 190
Ser Asp Ile Arg Gly Ala Leu Leu Lys Phe Ala Lys Asp Gln Val Gly
195 200 205
Ser Arg Phe Ile Gln Gln Glu Leu Ala Ser Ser Lys Asp Arg Phe Glu
210 215 220
Lys Asp Ser Ile Phe Asp Glu Val Val Ser Asn Ala Asp Glu Leu Val
225 230 235 240
Asp Asp Ile Phe Gly Asn Tyr Val Val Gln Lys Phe Phe Glu Tyr Gly
245 250 255
Glu Glu Arg His Trp Ala Arg Leu Val Asp Ala Ile Ile Asp Arg Val
260 265 270
Pro Glu Tyr Ala Phe Gln Met Tyr Ala Cys Arg Val Leu Gln Lys Ala
275 280 285
Leu Glu Lys Ile Asn Glu Pro Leu Gln Ile Lys Ile Leu Ser Gln Ile
290 295 300
Arg His Val Ile His Arg Cys Met Lys Asp Gln Asn Gly Asn His Val
305 310 315 320
Val Gln Lys Ala Ile Glu Lys Val Ser Pro Gln Tyr Val Gln Phe Ile
325 330 335
Val Asp Thr Leu Leu Glu Ser Ser Asn Thr Ile Tyr Glu Met Ser Val
340 345 350
Asp Pro Tyr Gly Cys Arg Val Val Gln Arg Cys Leu Glu His Cys Ser
355 360 365
Pro Ser Gln Thr Lys Pro Val Ile Gly Gln Ile His Lys Arg Phe Asp
370 375 380
Glu Ile Ala Asn Asn Gln Tyr Gly Asn Tyr Val Val Gln His Val Ile
385 390 395 400
Glu His Gly Ser Glu Glu Asp Arg Met Val Ile Val Thr Arg Val Ser
405 410 415
Asn Asn Leu Phe Glu Phe Ala Thr His Lys Tyr Ser Ser Asn Val Ile
420 425 430
Glu Lys Cys Leu Glu Gln Gly Ala Val Tyr His Lys Ser Met Ile Val
435 440 445
Gly Ala Ala Cys His His Gln Glu Gly Ser Val Pro Ile Val Val Gln
450 455 460
Met Met Lys Asp Gln Tyr Ala Asn Tyr Val Val Gln Lys Met Phe Asp
465 470 475 480
Gln Val Thr Ser Glu Gln Arg Arg Glu Leu Ile Leu Thr Val Arg Pro
485 490 495
His Ile Pro Val Leu Arg Gln Phe Pro His Gly Lys His Ile Leu Ala
500 505 510
Lys Leu Glu Lys Tyr Phe Gln Lys Pro Ala Val Met Ser Tyr Pro Tyr
515 520 525
Gln Asp Met Gln Gly Ser His
530 535
<210> 216
<211> 703
<212> PRT
<213> 未知的
<220>
<223> PUF9
<400> 216
Met Ala Asp Pro Asn Trp Ala Tyr Ala Pro Pro Thr Asn Tyr Tyr Ala
1 5 10 15
Asp His Ser Ile Ala Lys Pro Ile Met Ile Ser Gly Gly His Pro Ser
20 25 30
Gln Asp Gln Gly His Ser Pro Lys Ser Glu Ser Phe Gly Gln Ser Val
35 40 45
Thr Thr Ala Phe Asn Gly Met Val Asp Asn Leu Val Gly Ser Pro Ser
50 55 60
Ser Ser Val Gln Gln Arg Asn Tyr Phe Thr Thr Thr Pro Phe Pro Ile
65 70 75 80
Ser Arg Ser Pro Asn Asp Arg Asn Asp Asp Lys Ile Met Gly Asn Gly
85 90 95
Ser Tyr Gly Val Pro Ile Pro Ile Pro Gln Asp Gly Val Pro Gln Gly
100 105 110
Thr Pro Asp Phe Gln Met Thr Pro Phe Leu Gln Gln Gly Gly His Leu
115 120 125
Ile Gly Gly Ser Pro Asn Gly Pro Val Gln Val Ser Gly Asn Trp Tyr
130 135 140
Ser Gly Gly Ala Gly Ile Phe Ser Thr Met Gln Gln Ala Asp Pro Ser
145 150 155 160
Asn Gly Met Pro Gly Met Ala Ala Glu Phe Val Asn Asn Glu Asn Gly
165 170 175
Met Pro Gly Pro Asn Gly Met His Gln Gln Ala Met Ile Ser Gly Ser
180 185 190
Pro Pro Phe Pro Tyr Gln Asn Met Met Asn Leu Thr Thr Ser Phe Gly
195 200 205
Ala Met Gly Leu Gly Pro Gln Gln Ile Gln Gln Arg Asp Pro Gln Met
210 215 220
Phe Gln Gln Pro Ile Leu His Glu Pro Ile Gln Gly Met Ala Gln Asn
225 230 235 240
Gly Phe Gly Gln Gln Val Phe Phe Thr Gln Met Gln Asn Gln Gln His
245 250 255
Pro Gln Gly Gln Ala Gln Gln Gln Leu Gln Gln Leu Ala Gln Gln His
260 265 270
Gln Gln Gln Gln Asn Ser Gln Gln Phe Phe Gly Gln Gly Pro Asn Gly
275 280 285
Met Gly Asn Gly Gly Val Met Asn Asp Trp Ser Gln Arg Ser Phe Gly
290 295 300
Met Pro Gln Gln Gln Ala Gln Gln Asn Gly Leu Pro Pro Asn Phe Ser
305 310 315 320
Gln Asn Pro Pro Arg Arg Arg Gly Pro Glu Asp Pro Asn Gly Gln Thr
325 330 335
Pro Lys Thr Leu Gln Asp Ile Lys Asn Asn Val Ile Glu Phe Ala Lys
340 345 350
Asp Gln His Gly Ser Arg Phe Ile Gln Gln Lys Leu Glu Arg Ala Ser
355 360 365
Leu Arg Asp Lys Ala Ala Ile Phe Thr Pro Val Leu Glu Asn Ala Glu
370 375 380
Glu Leu Met Thr Asp Val Phe Gly Asn Tyr Val Ile Gln Lys Phe Phe
385 390 395 400
Glu Phe Gly Asn Asn Glu Gln Arg Asn Gln Leu Val Gly Thr Ile Arg
405 410 415
Gly Asn Val Met Lys Leu Ala Leu Gln Met Tyr Gly Cys Arg Val Ile
420 425 430
Gln Lys Ala Leu Glu Tyr Val Glu Glu Lys Tyr Gln His Glu Ile Leu
435 440 445
Gly Glu Met Glu Gly Gln Val Leu Lys Cys Val Lys Asp Gln Asn Gly
450 455 460
Asn His Val Ile Gln Lys Val Ile Glu Arg Val Glu Pro Glu Arg Leu
465 470 475 480
Gln Phe Ile Ile Asp Ala Phe Thr Lys Asn Asn Ser Asp Asn Val Tyr
485 490 495
Thr Leu Ser Val His Pro Tyr Gly Cys Arg Val Ile Gln Arg Val Leu
500 505 510
Glu Tyr Cys Asn Glu Glu Gln Lys Gln Pro Val Leu Asp Ala Leu Gln
515 520 525
Ile His Leu Lys Gln Leu Val Leu Asp Gln Tyr Gly Asn Tyr Val Ile
530 535 540
Gln His Val Ile Glu His Gly Ser Pro Ser Asp Lys Glu Gln Ile Val
545 550 555 560
Gln Asp Val Ile Ser Asp Asp Leu Leu Lys Phe Ala Gln His Lys Phe
565 570 575
Ala Ser Asn Val Ile Glu Lys Cys Leu Thr Phe Gly Gly His Ala Glu
580 585 590
Arg Asn Leu Ile Ile Asp Lys Val Cys Gly Asp Pro Asn Asp Pro Ser
595 600 605
Pro Pro Leu Leu Gln Met Met Lys Asp Pro Phe Ala Asn Tyr Val Val
610 615 620
Gln Lys Met Leu Asp Val Ala Asp Pro Gln His Arg Lys Lys Ile Thr
625 630 635 640
Leu Thr Ile Lys Pro His Ile Ala Thr Leu Arg Lys Tyr Asn Phe Gly
645 650 655
Lys His Ile Leu Leu Lys Leu Glu Lys Tyr Phe Ala Lys Gln Ala Pro
660 665 670
Ala Asn Ser Ser Asn Ser Ser Ser Asn Asp Gln Ile Tyr Glu His Ser
675 680 685
Pro Phe Asp Ile Pro Leu Gly Ala Asp Phe Ser Asn His Pro Phe
690 695 700

Claims (20)

1.一种组合物，所述组合物包含编码RNA指导的靶RNA结合融合蛋白的核酸序列，所述融合蛋白包含(a)第一RNA结合多肽或其部分；以及(b)第二RNA结合多肽，其中在通过gRNA序列指导时，所述第一RNA结合多肽结合靶RNA，并且其中所述第二RNA结合多肽包含RNA-核酸酶活性。
2.根据权利要求1所述的组合物，其中所述第一RNA结合多肽或其部分是CRISPR/Cas多肽或其部分。
3.根据权利要求2所述的组合物，其中所述CRISPR/Cas多肽或其部分选自Cas9、Cpf1、Cas13a、Cas13b、Cas13c和CasRX/Cas13d，其中所述CRISPR/Cas多肽具有天然的、降低的或无效的活性。
4.根据权利要求1所述的组合物，其中所述第二RNA结合多肽以与RNA缔合的方式结合RNA。
5.根据权利要求4所述的组合物，其中所述第二RNA结合多肽以切割RNA的方式与RNA缔合。
6.根据权利要求1所述的组合物，其中所述核酸序列包含启动子。
7.根据权利要求6所述的组合物，其中所述启动子是组成型启动子或组织特异性启动子。
8.根据权利要求1所述的组合物，其中所述核酸序列还包含gRNA序列，其中所述gRNA序列包含特异性结合RNA分子内的靶序列的间隔子序列和与所述第一RNA结合多肽特异性结合的支架序列。
9.根据权利要求8所述的组合物，其中所述间隔子序列包含含有选自以下的序列的至少1、2、3、4、5、6或7个重复的序列：CUG(SEQ ID NO:18)、CCUG(SEQ ID NO:19)、CAG(SEQ IDNO:80)、GGGGCC(SEQ ID NO:81)及其组合。
10.根据权利要求8所述的组合物，其中所述核酸序列包含驱动所述gRNA序列的表达的启动子。
11.根据权利要求9所述的组合物，其中所述启动子是聚合酶III启动子。
12.根据权利要求10所述的组合物，其中所述聚合酶III启动子是U6启动子。
13.根据权利要求1或9所述的组合物，其中所述启动子是tRNA启动子。
14.根据权利要求1或9所述的组合物，其中所述融合蛋白包含NLS、NES或标签。
15.一种载体，其包含根据权利要求1或8所述的组合物。
16.根据权利要求15所述的载体，其中所述载体选自：腺相关病毒、逆转录病毒、慢病毒、腺病毒、纳米颗粒、胶束、脂质体、阳离子脂质体/DNA复合物、聚合物囊泡、聚合物/DNA复合物和树枝状聚合物。
17.一种细胞，其包含根据权利要求15所述的载体。
18.根据权利要求1所述的组合物，其中所述第二RNA结合多肽选自：RNA酶1、RNA酶4、RNA酶6、RNA酶7、RNA酶8、RNA酶2、RNA酶6PL、RNA酶L、RNA酶T2、RNA酶11、RNA酶T2样蛋白、NOB1、ENDOV、ENDOG、ENDOD1、hFEN1、hSLFN14、hLACTB2、APEX2、ANG、HRSP12、ZC3H12A、RIDA、PDL6、NTHL、KIAA0391、APEX1、AGO2、EXOG、ZC3H12D、ERN2、PELO、YBEY、CPSF4L、hCG_2002731、ERCC1、RAC1、RAA1、RAB1、DNA2、FLJ35220、FLJ13173、ERCC4、RNA酶1(K41R)、RNA酶1(K41R、D121E)、RNA酶1(K41R、D121E、H119N)、RNA酶1(H119N)、RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N)、RNA酶1(R39D、N67D、N88A、G89D、R91D、H119N、K41R、D121E)、RNA酶1(R39D、N67D、N88A、G89D、R91D)、TENM1、TENM2、RNA酶K、TALEN和ZNF638。
19.一种组合物，其包含：
(a)指导RNA(gRNA)序列，所述指导RNA(gRNA)序列包含特异性结合RNA分子内的靶序列的间隔子序列和与所述第一RNA结合多肽特异性结合的支架序列；
(b)编码融合蛋白的核酸序列，所述融合蛋白包含第一RNA结合多肽和编码第二RNA结合多肽的序列，
其中所述第一RNA结合多肽和所述第二RNA结合多肽都不包含显著DNA-核酸酶活性，
其中所述第一RNA结合多肽与所述第二RNA结合多肽不相同，并且其中所述第二RNA结合多肽包含RNA-核酸酶活性。
20.一种用于修饰靶RNA分子或由所述RNA分子编码的蛋白质的表达水平的方法，所述方法包括在适合于融合蛋白或其部分与所述RNA分子结合的条件下使根据权利要求19所述的组合物与所述RNA分子接触。
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