CN111454367B - 一种碱基编辑分子及其用途 - Google Patents
一种碱基编辑分子及其用途 Download PDFInfo
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- CN111454367B CN111454367B CN201910053295.1A CN201910053295A CN111454367B CN 111454367 B CN111454367 B CN 111454367B CN 201910053295 A CN201910053295 A CN 201910053295A CN 111454367 B CN111454367 B CN 111454367B
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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Abstract
本发明涉及生物技术领域,特别是涉及一种融合蛋白及其用途。本发明提供一种融合蛋白,包括hA3A片段、dCas12a片段和UGI片段。本发明克服了现有碱基编辑器无法在A/T富集区域内进行精准高效碱基编辑的问题,利用可识别A/T富集PAM序列的CRISPR/Cas蛋白Cas12a(Cpf1)和人胞嘧啶脱氨酶3A(human APOBEC3A,hA3A)发展出新型碱基编辑器,在A/T富集区域内实现了高效率和高精准度的定向碱基编辑,有助于在各物种基因组更为广泛的位点实现精准高效的碱基编辑,并极大地扩充我们对于碱基编辑器的应用,特别是在医疗领域对相关疾病进行精准基因治疗方面。
Description
技术领域
本发明涉及生物技术领域,特别是涉及一种融合蛋白及其用途。
背景技术
基因组编辑技术指利用可设计的核酸酶(分子剪刀)通过碱基插入、缺失或置换等方式,对生物体基因组DNA特定片段进行改造从而达到对目标基因进行编辑的一种基因工程技术。利用基因组编辑技术对细胞进行遗传学操纵,可广泛的应用于生命科学基础研究、生物技术开发、农业技术开发以及医药研发领域。例如:直接在体内校正引起遗传疾病的基因突变,将能够从根本上治疗遗传疾病;对农作物进行精确的基因工程改造,使其产量提高或能够抵抗环境污染或病原体的感染;对微生物基因组进行精准改造,从而促进可再生生物能源的开发等。
CRISPR/Cas(Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein)基因组编辑系统自问世以来,就有着其它基因组编辑技术无可比拟的优势,被认为能够在活细胞中广泛使用,并是迄今为止最有效、最便捷的基因组编辑系统。Cas9核酸酶利用引导RNA(guide RNA,gRNA)可在多种细胞的基因组特定靶点定位,对其进行切割从而产生DNA双链断裂(double strand breaks,DSBs),然后利用细胞内源的DNA修复机制来实现编辑。根据不同DNA修复通路的激活,基因组编辑将会导致基因的失活或者突变的校正。通常来说,有两种主要的修复机制会被DNA双链断裂所激活,一种是非同源末端连接(non-homologous end joining,NHEJ),另一种是同源性介导修复(homology-directed repair,HDR)。做为DNA双链断裂最主要的修复通路,NHEJ在修复过程中能在DSB附近的基因组位点引入随机的碱基插入或缺失,从而导致基因的失活。与NHEJ相反,当HDR被激活时能够以外源性供体DNA作为模版,利用同源重组机制将外源性供体DNA的序列替换靶点基因组DNA的序列,从而完成基因突变的校正。但实际上,由于同源重组机制本身的局限性,HDR介导的基因校正效率一直很低(通常小于5%)。因此,限制了CRISPR/Cas基因组编辑工具从科研向应用的转化,尤其是在精准基因治疗方面的应用,这也是基因编辑领域的一大难题。
为了提高基因突变的校正效率,碱基编辑器(base editor,BE)在近期内应运而生。这种碱基编辑器将CRISPR/Cas系统和APOBEC胞嘧啶脱氨酶家族成员整合在一起,可执行将胞嘧啶(cytosine,C)编辑为胸腺嘧啶(thymine,T)的功能。目前已经成功开发的碱基编辑器包括将Cas9蛋白与大鼠胞嘧啶脱氨酶1(rat APOBEC1,rA1)或者人胞嘧啶脱氨酶3A(human APOBEC3A,hA3A)整合在一起。然而,Cas9蛋白主要识别鸟嘌呤G/胞嘧啶C富集区域的PAM序列,这一特点限制了Cas9碱基编辑器在腺嘌呤A/胸腺嘧啶T富集区域内开展碱基编辑。
发明内容
鉴于以上所述现有技术的缺点,本发明的目的在于提供一种融合蛋白及其用途,用于解决现有技术中的问题。
为实现上述目的及其他相关目的,本发明一方面提供一种融合蛋白,包括hA3A片段、dCas12a片段和UGI片段。
在本发明一些实施方式中,所述hA3A片段的氨基酸序列包括:
a)如SEQ ID NO.31~42其中之一所示的氨基酸序列;或,
b)与SEQ ID NO.31~42其中之一具有80%以上序列相似性、且具有a)所限定的氨基酸序列的功能的氨基酸序列,优选为具有胞苷脱氨酶活性。
在本发明一些实施方式中,所述dCas12a片段的氨基酸序列包括:
c)如SEQ ID NO.43~45其中之一所示的氨基酸序列;或,
d)与SEQ ID NO.43~45其中之一具有80%以上序列相似性的氨基酸序列、且具有c)所限定的氨基酸序列的功能;优选为具有的DNA结合活性、且完全丧失了DNA剪切活性,更优选为具有识别腺嘌呤A/胸腺嘧啶T富集PAM序列的功能,更优选为C/T ratio≤50%的PAM序列。
在本发明一些实施方式中,所述UGI片段的氨基酸序列包括:
e)如SEQ ID NO.46所示的氨基酸序列;或,
f)与SEQ ID NO.46具有80%以上序列相似性的氨基酸序列、且具有e)所限定的氨基酸序列的功能;优选为具有尿嘧啶糖基化酶活性。
在本发明一些实施方式中,所述融合蛋白自5’端至3’端依次包括包括hA3A片段、dCas12a片段和UGI片段。
在本发明一些实施方式中,所述融合蛋白的氨基酸序列如SEQ ID No.47~57所示。
在本发明一些实施方式中,所述融合蛋白还包括NLS片段。
本发明另一方面提供一种分离的多核苷酸,编码所述的融合蛋白。
本发明另一方面提供一种碱基编辑体系,包括所述的融合蛋白,所述碱基编辑体系还包括sgRNA。
本发明另一方面提供一种表达系统,所述表达系统包括能够表达所述的碱基编辑体系的宿主细胞。
在本发明一些实施方式中,所述表达系统包括含有编码所述融合蛋白的多核苷酸的表达载体的宿主细胞、或染色体中整合有编码所述融合蛋白的多核苷酸的宿主细胞。
在本发明一些实施方式中,所述表达系统包括含有编码所述sgRNA的多核苷酸的表达载体的宿主细胞、或染色体中整合有编码所述sgRNA的多核苷酸的宿主细胞。
在本发明一些实施方式中,所述表达系统为包括目标基因的目标区域的宿主细胞。
在本发明一些实施方式中,所述宿主细胞选自真核细胞以及原核细胞。
在本发明一些实施方式中,所述宿主细胞选自人细胞。
在本发明一些实施方式中,所述宿主细胞选自人胎肾细胞。
在本发明一些实施方式中,所述宿主细胞选自人胎肾HEK293T细胞。
本发明另一方面提供所述的融合蛋白、所述的多核苷酸、所述的碱基编辑体系或所述的表达系统在基因编辑中的用途。
在本发明一些实施方式中,所述用途具体为在真核生物的基因编辑中的用途。
本发明另一方面提供一种基因编辑方法,包括:通过所述的融合蛋白、或所述的碱基编辑体系进行基因编辑。
在本发明一些实施方式中,所述基因编辑方法包括:在适当条件下培养所述的表达系统。
在本发明一些实施方式中,所述基因编辑方法为体外基因编辑方法。
在本发明一些实施方式中,所述基因编辑方法的编辑窗口≤23个、≤20个、≤15个、≤12个、≤9个、或≤6个碱基。
附图说明
图1显示为本发明实施例1测序结果分析示意图。
图2显示为本发明实施例1测序结果分析示意图。
图3显示为本发明实施例2测序结果分析示意图。
图4显示为本发明实施例2测序结果分析示意图。
图5显示为本发明实施例3测序结果分析示意图。
图6显示为本发明实施例3测序结果分析示意图。
图7显示为本发明实施例1sanger测序结果示意图。
图8显示为本发明实施例1sanger测序结果示意图。
图9显示为本发明实施例2sanger测序结果示意图。
图10显示为本发明实施例2sanger测序结果示意图。
图11显示为本发明实施例3sanger测序结果示意图。
图12显示为本发明实施例3sanger测序结果示意图。
具体实施方式
本发明发明人经过大量探索性研究,提供了一种融合蛋白,所述融合蛋白是一种新的碱基编辑分子,所述融合蛋白可以包括hA3A片段、dCas12a片段和UGI片段,可以实现对sgRNA靶点区域内C的高效率的碱基编辑,在此基础上完成了本发明。
本发明第一方面提供一种融合蛋白,包括hA3A(人胞嘧啶脱氨酶3A,humanAPOBEC3A)片段、dCas12a(dCpf1)片段和UGI片段。本发明所提供的融合蛋白可以是一种碱基编辑分子,其可以与靶向靶点区域的sgRNA相配合,实现高效率、高精度的C-to-T的碱基编辑。
本发明所提供的融合蛋白中,所述hA3A片段的氨基酸序列可以包括:a)如SEQ IDNO.31~42其中之一所示的氨基酸序列;或,b)与SEQ ID NO.31~42其中之一具有80%以上序列相似性、且具有a)所限定的氨基酸序列的功能的氨基酸序列;具体的,所述b)中的氨基酸序列具体指:如SEQ ID No.31~42其中之一所示的氨基酸序列经过取代、缺失或者添加一个或多个(具体可以是1-50、1-30个、1-20个、1-10个、1-5个、1-3个、1个、2个、或3个)氨基酸而得到的,或者在N-末端和/或C-末端添加一个或多个(具体可以是1-50个、1-30个、1-20个、1-10个、1-5个、1-3个、1个、2个、或3个)氨基酸而得到的,且具有氨基酸如SEQ ID No.31~42其中之一所示的多肽片段的功能的多肽片段,例如,可以是具有胞苷脱氨酶活性,更具体可以是将胞嘧啶(cytosine,C)脱氨产生尿嘧啶(uracil,U)的功能。所述b)中的氨基酸序列可与SEQ ID No.31~42其中之一具有80%、85%、90%、93%、95%、97%、或99%以上的相似性。
本发明所提供的融合蛋白中,所述dCas12a片段可以来源于包括但不限于AsCas12a(U2UMQ6.1)、LbCas12a(WP_051666128.1)、或FnCas12a(A0Q7Q2.1)等,所述dCas12a片段的氨基酸序列可以包括:c)如SEQ ID NO.43~45其中之一所示的氨基酸序列;或,d)与SEQ ID NO.43~45其中之一具有80%以上序列相似性、且具有c)所限定的氨基酸序列的功能的氨基酸序列。具体的,所述d)中的氨基酸序列具体指:如SEQ ID No.43~45其中之一所示的氨基酸序列经过取代、缺失或者添加一个或多个(具体可以是1-50、1-30个、1-20个、1-10个、1-5个、1-3个、1个、2个、或3个)氨基酸而得到的,或者在N-末端和/或C-末端添加一个或多个(具体可以是1-50个、1-30个、1-20个、1-10个、1-5个、或1-3个、1个、2个、或3个)氨基酸而得到的,且具有氨基酸如SEQ ID No.43~45其中之一所示的多肽片段的功能的多肽片段,例如,可以是具有DNA结合活性、且完全丧失了DNA剪切活性,更优选为具有识别腺嘌呤A/胸腺嘧啶T富集PAM序列的功能(具体可以是C/T ratio≤50%的PAM序列)。所述d)中的氨基酸序列可与SEQ ID No.43~45其中之一具有80%、85%、90%、93%、95%、97%、或99%以上的相似性。
本发明所提供的融合蛋白中,所述UGI片段的氨基酸序列可以包括:e)如SEQ IDNO.46所示的氨基酸序列;或,f)与SEQ ID NO.46具有80%以上序列相似性、且具有e)所限定的氨基酸序列的功能的氨基酸序列;具体的,所述f)中的氨基酸序列具体指:如SEQ IDNo.46所示的氨基酸序列经过取代、缺失或者添加一个或多个(具体可以是1-50、1-30个、1-20个、1-10个、1-5个、1-3个、1个、2个、或3个)氨基酸而得到的,或者在N-末端和/或C-末端添加一个或多个(具体可以是1-50个、1-30个、1-20个、1-10个、1-5个、1-3个、1个、2个、或3个)氨基酸而得到的,且具有氨基酸如SEQ ID No.46所示的多肽片段的功能的多肽片段,例如,具有尿嘧啶糖基化酶活性。所述f)中的氨基酸序列可与SEQ ID No.46具有80%、85%、90%、93%、95%、97%、或99%以上的相似性。
SEQ ID No.31~46的具体序列如表1所示:
表1
本发明所提供的融合蛋白中,所述的取代、缺失或者添加可以是保守氨基酸取代。所述“保守氨基酸取代”具体可以是指氨基酸残基被其他具有相似侧链的氨基酸残基取代的情况。具有相似侧链的氨基酸残基家族对于本领域技术人员来说应该是已知的,例如,可以是包括但不限于碱性侧链(例如赖氨酸,精氨酸,组氨酸),酸性侧链(例如天冬氨酸,谷氨酸),不带电荷的极性侧链(例如,甘氨酸,天冬酰胺,谷氨酰胺,丝氨酸,苏氨酸,酪氨酸,半胱氨酸),非极性侧链(例如丙氨酸,缬氨酸,亮氨酸,异亮氨酸,脯氨酸,苯丙氨酸,甲硫氨酸,色氨酸)异亮氨酸)和芳族侧链(例如酪氨酸,苯丙氨酸,色氨酸,组氨酸)等家族。保守型氨基酸取代更具体可以包括但不限于下表中所列的具体情况,表2(氨基酸相似度矩阵)中的数字表示两个氨基酸之间的相似度,当数字大于等于0时认为是保守氨基酸取代,表3为示例性的保守氨基酸取代的方案。
表2
C | G | P | S | A | T | D | E | N | Q | H | K | R | V | M | I | L | F | Y | W | |
W | -8 | -7 | -6 | -2 | -6 | -5 | -7 | -7 | -4 | -5 | -3 | -3 | 2 | -6 | -4 | -5 | -2 | 0 | 0 | 17 |
Y | 0 | -5 | -5 | -3 | -3 | -3 | -4 | -4 | -2 | -4 | 0 | -4 | -5 | -2 | -2 | -1 | -1 | 7 | 10 | |
F | -4 | -5 | -5 | -3 | -4 | -3 | -6 | -5 | -4 | -5 | -2 | -5 | -4 | -1 | 0 | 1 | 2 | 9 | ||
L | -6 | -4 | -3 | -3 | -2 | -2 | -4 | -3 | -3 | -2 | -2 | -3 | -3 | 2 | 4 | 2 | 6 | |||
I | -2 | -3 | -2 | -1 | -1 | 0 | -2 | -2 | -2 | -2 | -2 | -2 | -2 | 4 | 2 | 5 | ||||
M | -5 | -3 | -2 | -2 | -1 | -1 | -3 | -2 | 0 | -1 | -2 | 0 | 0 | 2 | 6 | |||||
V | -2 | -1 | -1 | -1 | 0 | 0 | -2 | -2 | -2 | -2 | -2 | -2 | -2 | 4 | ||||||
R | -4 | -3 | 0 | 0 | -2 | -1 | -1 | -1 | 0 | 1 | 2 | 3 | 6 | |||||||
K | -5 | -2 | -1 | 0 | -1 | 0 | 0 | 0 | 1 | 1 | 0 | 5 | ||||||||
H | -3 | -2 | 0 | -1 | -1 | -1 | 1 | 1 | 2 | 3 | 6 | |||||||||
Q | -5 | -1 | 0 | -1 | 0 | -1 | 2 | 2 | 1 | 4 | ||||||||||
N | -4 | 0 | -1 | 1 | 0 | 0 | 2 | 1 | 2 | |||||||||||
E | -5 | 0 | -1 | 0 | 0 | 0 | 3 | 4 | ||||||||||||
D | -5 | 1 | -1 | 0 | 0 | 0 | 4 | |||||||||||||
T | -2 | 0 | 0 | 1 | 1 | 3 | ||||||||||||||
A | -2 | 1 | 1 | 1 | 2 | |||||||||||||||
S | 0 | 1 | 1 | 1 | ||||||||||||||||
P | -3 | -1 | 6 | |||||||||||||||||
G | -3 | 5 | ||||||||||||||||||
C | 12 |
表3
本发明所提供的融合蛋白中,所述融合蛋白自5’端至3’端可以依次包括包括hA3A(人胞嘧啶脱氨酶3A,human APOBEC3A)片段、dCas12a(dCpf1)片段和UGI片段。在本发明一具体实施例中,所述融合蛋白的氨基酸序列可以如SEQ ID No.47~57所示。
表4
本发明所提供的融合蛋白中,所述融合蛋白还可以包括NLS(核定位序列)片段,所述NLS片段主要可以用于引导蛋白质进入细胞核,从而可以实现对目标区域的碱基编辑。本领域技术人员可根据目标细胞(例如,真核细胞等,更具体可以是人胎肾细胞等,更具体可以是HEK293T细胞等),选择合适的NLS片段,例如,所述NLS片段的氨基酸序列可以是PKKKRKV(SEQ ID No.58)。
本发明第二方面提供一种分离的多核苷酸,编码本发明第一方面所提供的融合蛋白。
本发明第三方面提供一种碱基编辑体系,包括本发明第一方面所提供的融合蛋白,所述碱基编辑体系还可以包括sgRNA。本领域技术人员可以根据基因的目标编辑区域,选择合适的靶向目标区域的sgRNA。例如,所述sgRNA的序列通常可以与目标区域至少部分互补,从而可以与所述融合蛋白相配合,将所述融合蛋白定位到目标区域,实现目标区域的碱基编辑,具体可以是胞嘧啶脱氨基反应,即将胞嘧啶(cytosine,C)编辑为胸腺嘧啶(thymine,T)。在本发明一具体实施例中,所述sgRNA可以靶向人基因组DYRK1A、人基因组SITE6、人基因组RUNX1等。
本发明第四方面提供一种表达系统,所述表达系统包括能够表达所述碱基编辑体系的宿主细胞,具体可以包括能够表达所述融合蛋白和所述sgRNA的宿主细胞。从而可以通过sgRNA靶向目标区域,并进一步配合所述融合蛋白,将所述融合蛋白定位到目标区域(例如,宿主细胞的目标基因的目标区域),实现目标区域的碱基编辑。使所述表达系统能够表达所述融合蛋白和所述sgRNA的方法对于本领域技术人员来说应该是已知的,例如,可以使所述表达系统包括含有编码所述融合蛋白的多核苷酸的表达载体的宿主细胞、或染色体中整合有编码所述融合蛋白的多核苷酸的宿主细胞;再例如,可以使所述表达系统包括含有编码所述sgRNA的多核苷酸的表达载体的宿主细胞、或染色体中整合有编码所述sgRNA的多核苷酸的宿主细胞。所述表达系统还可以是包括目标基因的目标区域的宿主细胞。在本发明一具体实施例中,所述目标基因可以是包括但不限于人基因组DYRK1A、人基因组SITE6、人基因组RUNX1等。在本发明另一具体实施例中,所述宿主细胞可以是真核细胞或原核细胞,更具体可以是人细胞等,更具体可以是人胎肾,更具体可以是人胎肾HEK293T细胞等。本领域技术人员可以根据宿主细胞的种类,选择合适的表达载体,例如,所述表达载体可以是包括但不限于pCMV、pcDNA、PGL3等。所述表达系统中,所述宿主细胞可以表达所述融合蛋白和/或所述sgRNA,从而可以将所述融合蛋白定位到目标区域,实现目标区域的碱基编辑。
本发明第五方面提供本发明第一方面所提供的融合蛋白、或本发明第二方面所提供的多核苷酸、本发明第三方面所提供的碱基编辑体系或本发明第四方面所提供的表达系统在基因编辑中的用途,优选为真核生物的基因编辑中的用途,所述真核生物具体可以是包括但不限于真菌、植物、动物、或人等。在本发明一具体实施例中,本编辑的目标基因可以是包括但不限于人基因组DYRK1A、人基因组SITE6、人基因组RUNX1等。
本发明第六方面提供一种基因编辑方法,所述基因编辑方法可以为体外基因编辑方法,所述基因编辑方法可以包括:通过本发明第一方面所提供的融合蛋白、或本发明第三方面所提供的碱基编辑体系进行基因编辑。例如,所述基因编辑方法可以包括:在适当条件下培养本发明第四方面所提供的表达系统。在本发明一优选实施例中,编辑窗口可以是≤23个、≤20个、≤15个、≤12个、≤9个、或≤6个碱基的范围,实现了更为精准的碱基编辑。
综上所述,本发明克服了现有碱基编辑器无法在A/T富集区域内进行精准高效碱基编辑的问题,利用可识别A/T富集PAM序列的CRISPR/Cas蛋白Cas12a(Cpf1)和人胞嘧啶脱氨酶3A(human APOBEC3A,hA3A)发展出新型碱基编辑器,在A/T富集区域内实现了高效率和高精准度的定向碱基编辑,有助于在各物种基因组更为广泛的位点实现精准高效的碱基编辑,并极大地扩充我们对于碱基编辑器的应用,特别是在医疗领域对相关疾病进行精准基因治疗方面。
以下通过特定的具体实例说明本发明的实施方式,本领域技术人员可由本说明书所揭露的内容轻易地了解本发明的其他优点与功效。本发明还可以通过另外不同的具体实施方式加以实施或应用,本说明书中的各项细节也可以基于不同观点与应用,在没有背离本发明的精神下进行各种修饰或改变。
在进一步描述本发明具体实施方式之前,应理解,本发明的保护范围不局限于下述特定的具体实施方案;还应当理解,本发明实施例中使用的术语是为了描述特定的具体实施方案,而不是为了限制本发明的保护范围;在本发明说明书和权利要求书中,除非文中另外明确指出,单数形式“一个”、“一”和“这个”包括复数形式。
当实施例给出数值范围时,应理解,除非本发明另有说明,每个数值范围的两个端点以及两个端点之间任何一个数值均可选用。除非另外定义,本发明中使用的所有技术和科学术语与本技术领域技术人员通常理解的意义相同。除实施例中使用的具体方法、设备、材料外,根据本技术领域的技术人员对现有技术的掌握及本发明的记载,还可以使用与本发明实施例中所述的方法、设备、材料相似或等同的现有技术的任何方法、设备和材料来实现本发明。
除非另外说明,本发明中所公开的实验方法、检测方法、制备方法均采用本技术领域常规的分子生物学、生物化学、染色质结构和分析、分析化学、细胞培养、重组DNA技术及相关领域的常规技术。这些技术在现有文献中已有完善说明,具体可参见Sambrook等MOLECULAR CLONING:A LABORATORY MANUAL,Second edition,Cold Spring HarborLaboratory Press,1989and Third edition,2001;Ausubel等,CURRENT PROTOCOLS INMOLECULAR BIOLOGY,John Wiley&Sons,New York,1987and periodic updates;theseries METHODS IN ENZYMOLOGY,Academic Press,San Diego;Wolffe,CHROMATINSTRUCTURE AND FUNCTION,Third edition,Academic Press,San Diego,1998;METHODS INENZYMOLOGY,Vol.304,Chromatin(P.M.Wassarman and A.P.Wolffe,eds.),AcademicPress,San Diego,1999;和METHODS IN MOLECULAR BIOLOGY,Vol.119,ChromatinProtocols(P.B.Becker,ed.)Humana Press,Totowa,1999等。
实施例1人基因组DYRK1A靶点利用一系列dCas12a-hA3A碱基编辑器实现高效且高精度的C-T碱基编辑
1.1实验材料
试剂及质粒:引物合成自生工生物工程(上海)股份有限公司;限制性内切酶、DNA连接酶、高保真DNA聚合酶购自NEB公司;质粒重组试剂盒Clone购自Vazyme公司;DNA胶回收试剂盒购自Corning公司;转染试剂LTX,购自Thermo Fisher公司;QuickExtractTM基因组DNA抽提试剂购自Illumina公司。
细胞株:人胎肾细胞HEK293T培养在加入了10%胎牛血清(Gbico),1%双抗的DMEM培养基(Gibco)中贴壁培养。
1.2实验方法
dCas12a-hA3A-BE表达载体的构建:
以puc57-hA3A(金斯瑞生物科技有限公司合成)为模板,利用引物对(核苷酸序列如SEQ ID NO.1和SEQ ID NO.2所示的引物对,各引物序列具体如表1所示,下同)进行PCR,得到hA3A的CDS序列,并且在两端带有与线性化载体同源的区段,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone 重组至经SacI和SmaI处理后产生的线性化dCas12a-BE载体中,得到表达载体dCas12a-hA3A-BE。
dCas12a-hA3A-BE-W98Y表达载体的构建:
以dCas12a-hA3A-BE为模板,利用引物对(核苷酸序列如SEQ ID NO.1和SEQ IDNO.4所示的引物对)和引物对(核苷酸序列如SEQ ID NO.2和SEQ ID NO.3所示的引物对)进行PCR,得到两段带有W98Y突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE载体中,得到表达载体dCas12a-hA3A-BE-W98Y。
dCas12a-hA3A-BE-W104A表达载体的构建:
以dCas12a-hA3A-BE为模板,利用引物对(核苷酸序列如SEQ ID NO.1和SEQ IDNO.6所示的引物对)和引物对(核苷酸序列如SEQ ID NO.5和SEQ ID NO.2所示的引物对)进行PCR,得到两段带有W104A突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE载体中,得到表达载体dCas12a-hA3A-BE-W104A。
dCas12a-hA3A-BE-P134Y表达载体的构建:
以dCas12a-hA3A-BE为模板,利用引物对(核苷酸序列如SEQ ID NO.1和SEQ IDNO.8所示的引物对)和引物对(核苷酸序列如SEQ ID NO.7和SEQ ID NO.2所示的引物对)进行PCR,得到两段带有P134Y突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE载体中,得到表达载体dCas12a-hA3A-BE-P134Y。
dCas12a-hA3A-BE-W98Y-W104A表达载体的构建:
以dCas12a-hA3A-BE为模板,利用引物对(核苷酸序列如SEQ ID NO.1和SEQ IDNO.10所示的引物对)和引物对(核苷酸序列如SEQ ID NO.9和SEQ ID NO.2所示的引物对)进行PCR,得到两段带有W98Y-W104A双突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE载体中,得到表达载体dCas12a-hA3A-BE-W98Y-W104A。
dCas12a-hA3A-BE-W98Y-P134Y表达载体的构建:
以dCas12a-hA3A-BE-W98Y为模板,利用引物对(核苷酸序列如SEQ ID NO.1和SEQID NO.8所示的引物对)和引物对(核苷酸序列如SEQ ID NO.7和SEQ ID NO.2所示的引物对)进行PCR,得到两段带有P134Y突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE-W98Y载体中,得到表达载体dCas12a-hA3A-BE-W98Y-P134Y。
dCas12a-hA3A-BE-W104A-P134Y表达载体的构建:
以dCas12a-hA3A-BE-W104A为模板,利用引物对(核苷酸序列如SEQ ID NO.1和SEQID NO.8所示的引物对)和引物对(核苷酸序列如SEQ ID NO.7和SEQ ID NO.2所示的引物对)进行PCR,得到两段带有P134Y突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE-W104A载体中,得到表达载体dCas12a-hA3A-BE-W104A-P134Y。
dCas12a-hA3A-BE-W98Y-W104A-Y130F表达载体的构建:
以dCas12a-hA3A-BE-W98Y-W104A为模板,利用引物对(核苷酸序列如SEQ ID NO.1和SEQ ID NO.12所示的引物对)和引物对(核苷酸序列如SEQ ID NO.11和SEQ ID NO.2所示的引物对)进行PCR,得到两段带有Y130F突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE-W98Y-W104A载体中,得到表达载体dCas12a-hA3A-BE-W98Y-W104A-Y130F。
dCas12a-hA3A-BE-W98Y-W104A-Y132D表达载体的构建:
以dCas12a-hA3A-BE-W98Y-W104A为模板,利用引物对(核苷酸序列如SEQ ID NO.1和SEQ ID NO.14所示的引物对)和引物对(核苷酸序列如SEQ ID NO.13和SEQ ID NO.2所示的引物对)进行PCR,得到两段带有Y132D突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE-W98Y-W104A载体中,得到表达载体dCas12a-hA3A-BE-W98Y-W104A-Y132D。
dCas12a-hA3A-BE-W104A-Y130F-P134Y表达载体的构建:
以dCas12a-hA3A-BE-W104A-P134Y为模板,利用引物对(核苷酸序列如SEQ IDNO.1和SEQ ID NO.16所示的引物对)和引物对(核苷酸序列如SEQ ID NO.15和SEQ ID NO.2所示的引物对)进行PCR,得到两段带有Y130F-P134Y双突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE-W104A-P134Y载体中,得到表达载体dCas12a-hA3A-BE-W104A-Y130F-P134Y。
dCas12a-hA3A-BE-W104A-Y132D-P134Y表达载体的构建:
以dCas12a-hA3A-BE-W104A-P134Y为模板,利用引物对(核苷酸序列如SEQ IDNO.1和SEQ ID NO.18所示的引物对)和引物对(核苷酸序列如SEQ ID NO.17和SEQ ID NO.2所示的引物对)进行PCR,得到两段带有Y132D-P134Y双突变且带有同源臂,同时带有与线性化载体同源区段的PCR产物,进行凝胶电泳纯化。经凝胶电泳纯化后,利用质粒重组试剂盒Clone将两个片段同时重组至经ApaI和SmaI处理后产生的线性化dCas12a-hA3A-BE-W104A-P134Y载体中,得到表达载体dCas12a-hA3A-BE-W104A-Y132D-P134Y。
sgRNA表达质粒的构建:
将核苷酸序列如SEQ ID NO.19和SEQ ID NO.20所示的引物退火,将退火产物利用T4DNA连接酶连入经限制性内切酶BsaI消化后的sgRNA表达载体pLb-Cas12a-pGL3-U6-sgRNA,得到靶向人基因组DYRK1A位点的sgRNA表达质粒sgDYRK1A。
表5
步骤1.2中质粒构建实验中扩增各种片段使用的PCR体系如下:HSDNA Polymerase(TAKARA)0.5μl;5×buffer 10μl;dNTPs 4μl;Forward Primer(10μM)1μl;Reverse Primer(10μM)1μl;Template 5ng;RNase-free water补至50μl。PCR程序如下:3min 94℃;32x(15sec 98℃,30sec 58℃,45s 72℃);7min 72℃。
真核细胞转染:
将sgDYRK1A和得到的序列正确的dCas12a-hA3A-BE、dCas12a-hA3A-BE-W98Y、dCas12a-hA3A-BE-W104A、dCas12a-hA3A-BE-P134Y、dCas12a-hA3A-BE-W98Y-W104A、dCas12a-hA3A-BE-W98Y-P134Y、dCas12a-hA3A-BE-W104A-P134Y、dCas12a-hA3A-BE-W98Y-W104A-Y130F、dCas12a-hA3A-BE-W98Y-W104A-Y132D、dCas12a-hA3A-BE-W104A-Y130F-P134Y、dCas12a-hA3A-BE-W104A-Y132D-P134Y分别以0.68ug:1μg的比例混合入200μlOpti-MEM中,加入1.68μl LIPOFECTAMINE plus,加入5.04ul LIPOFECTAMINE LTX,室温放置5分钟后加入500ul DMEM(+10%FBS)培养基和16万HEK293T细胞的24孔板中进行转染。12h后换成含1%双抗(青链霉素)的新鲜培养基。继续培养60h后收细胞。
基因组DNA抽提和PCR扩增:
利用QuickExtractTM试剂按照试剂操作说明抽提转染后HEK293T细胞的基因组DNA,将抽提得到的基因组DNA利用表2中所示的引物(核苷酸序列如SEQ ID NO.21和SEQ IDNO.22所示的引物)进行PCR扩增,并利用DNA胶回收试剂按照试剂操作说明对PCR产物进行切胶回收,用于DNA sanger测序。
表6
扩增基因组DNA使用PCR体系如下:HS DNA Polymerase(TAKARA)0.5μl;5×buffer 10μl;dNTPs 4μl;Forward Primer(10μM)1μl;Reverse Primer(10μM)1μl;Template 1ul;RNase-free water补至50μl。PCR程序如下:3min 94℃;32x(15sec 98℃,30sec 58℃,45s 72℃);7min 72℃。
DNA sanger测序:
对PCR产物进行DNA sanger测序。将对基因组DNA扩增得到的PCR产物分别使用Qubit Fluorometer和Aglient Bioanalyzer 2100进行浓度质检和纯度鉴定;质检合格的样品,送交苏州金唯智生物科技有限公司进行sanger测序。Sanger法是根据核苷酸在某一固定的点开始,随机在某一个特定的碱基处终止,并且在每个碱基后面进行荧光标记,产生以A、T、C、G结束的四组不同长度的一系列核苷酸,然后在尿素变性的PAGE胶上电泳进行检测,从而获得可见DNA碱基序列的一种方法。测序结果具体如图7和图8所示(两次重复实验数据)。EditR分析sanger测序结果:
利用EditR软件(https://moriaritylab.shinyapps.io/editr_v10/)对DNAsanger测序结果进行分析。EditR是2018年开发的一款网页版sanger测序结果分析软件(Kluesner M G,Nedveck D A,Lahr W S,et al.EditR:A Method to Quantify BaseEditing from Sanger Sequencing[J].The CRISPR Journal,2018,1(3):239-250.)。EditR是一款利用sanger测序信号,根据sgRNA序列,对DNA样品的测序结果进行处理,最后输出sgRNA靶位点处的碱基编辑效率的简洁、准确、高效的分析工具。分析结果如图1和图2所示。
实施例2人基因组SITE6靶点利用一系列dCas12a-hA3A碱基编辑器实现高效且高精度的C-T碱基编辑
2.1实验材料
试剂及质粒:同实施例1。
细胞株:同实施例1。
2.2实验方法
dCas12a-hA3A-BE表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W104A表达载体的构建:同实施例1。
dCas12a-hA3A-BE-P134Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y-W104A表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y-P134Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W104A-P134Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y-W104A-Y130F表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y-W104A-Y132D表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W104A-Y130F-P134Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W104A-Y132D-P134Y表达载体的构建:同实施例1。
sgRNA表达质粒的构建:
将核苷酸序列如SEQ ID NO.23和SEQ ID NO.24所示的引物退火,将退火产物利用T4 DNA连接酶连入经限制性内切酶BsaI消化后的sgRNA表达载体pLb-Cas12a-pGL3-U6-sgRNA,得到靶向人基因组SITE6位点的sgRNA表达质粒sgSITE6。
表7
质粒构建实验中扩增各种片段使用PCR体系如下:HS DNAPolymerase(TAKARA)0.5μl;5×buffer 10μl;dNTPs 4μl;Forward Primer(10μM)1μl;Reverse Primer(10μM)1μl;Template 5ng;RNase-free water补至50μl。PCR程序如下:3min 94℃;32x(15sec 98℃,30sec 58℃,45s 72℃);7min 72℃。
真核细胞转染:
将sgSITE6和得到的序列正确的dCas12a-hA3A-BE、dCas12a-hA3A-BE-W98Y、dCas12a-hA3A-BE-W104A、dCas12a-hA3A-BE-P134Y、dCas12a-hA3A-BE-W98Y-W104A、dCas12a-hA3A-BE-W98Y-P134Y、dCas12a-hA3A-BE-W104A-P134Y、dCas12a-hA3A-BE-W98Y-W104A-Y130F、dCas12a-hA3A-BE-W98Y-W104A-Y132D、dCas12a-hA3A-BE-W104A-Y130F-P134Y、dCas12a-hA3A-BE-W104A-Y132D-P134Y分别以0.68ug:1μg的比例混合入200μlOpti-MEM中,加入1.68μl LIPOFECTAMINE plus,加入5.04ul LIPOFECTAMINE LTX,室温放置5分钟后加入500ul DMEM(+10%FBS)培养基和16万HEK293T细胞的24孔板中进行转染。12h后换成含1%双抗的新鲜培养基。继续培养60h后收细胞。
基因组DNA抽提和PCR扩增:
利用QuickExtractTM试剂按照试剂操作说明抽提转染后HEK293T细胞的基因组DNA,将抽提得到的基因组DNA利用表4中所示的引物(核苷酸序列如SEQ ID NO.25和SEQ IDNO.26所示的引物)进行PCR扩增,并利用DNA胶回收试剂按照试剂操作说明对PCR产物进行切胶回收,用于DNA sanger测序。
表8
扩增基因组DNA使用PCR体系如下:HS DNA Polymerase(TAKARA)0.5μl;5×buffer 10μl;dNTPs 4μl;Forward Primer(10μM)1μl;Reverse Primer(10μM)1μl;Template 1ul;RNase-free water补至50μl。PCR程序如下:3min 94℃;32x(15sec 98℃,30sec 58℃,45s 72℃);7min 72℃。
DNA sanger测序:同实施例1。测序结果具体如图9和图10所示(两次重复实验数据)。
EditR分析sanger测序结果:同实施例1,分析结果如图3和图4所示。
实施例3人基因组RUNX1靶点利用一系列dCas12a-hA3A碱基编辑器实现高效且高精度的C-T碱基编辑
3.1实验材料
试剂及质粒:同实施例1。
细胞株:同实施例1。
3.2实验方法
dCas12a-hA3A-BE表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W104A表达载体的构建:同实施例1。
dCas12a-hA3A-BE-P134Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y-W104A表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y-P134Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W104A-P134Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y-W104A-Y130F表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W98Y-W104A-Y132D表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W104A-Y130F-P134Y表达载体的构建:同实施例1。
dCas12a-hA3A-BE-W104A-Y132D-P134Y表达载体的构建:同实施例1。
sgRNA表达质粒的构建:
将核苷酸序列如SEQ ID NO.27和SEQ ID NO.28所示的引物退火,将退火产物利用T4DNA连接酶连入经限制性内切酶BsaI消化后的sgRNA表达载体pLb-Cas12a-pGL3-U6-sgRNA,得到靶向人基因组RUNX1位点的sgRNA表达质粒sgRUNX1。
表9
质粒构建实验中扩增各种片段使用PCR体系如下:HS DNAPolymerase(TAKARA)0.5μl;5×buffer 10μl;dNTPs 4μl;Forward Primer(10μM)1μl;Reverse Primer(10μM)1μl;Template 5ng;RNase-free water补至50μl。PCR程序如下:3min 94℃;32x(15sec 98℃,30sec 58℃,45s 72℃);7min 72℃。
真核细胞转染:
将sgRUNX1和得到的序列正确的dCas12a-hA3A-BE、dCas12a-hA3A-BE-W98Y、dCas12a-hA3A-BE-W104A、dCas12a-hA3A-BE-P134Y、dCas12a-hA3A-BE-W98Y-W104A、dCas12a-hA3A-BE-W98Y-P134Y、dCas12a-hA3A-BE-W104A-P134Y、dCas12a-hA3A-BE-W98Y-W104A-Y130F、dCas12a-hA3A-BE-W98Y-W104A-Y132D、dCas12a-hA3A-BE-W104A-Y130F-P134Y、dCas12a-hA3A-BE-W104A-Y132D-P134Y分别以0.68ug:1μg的比例混合入200μlOpti-MEM中,加入1.68μl LIPOFECTAMINE plus,加入5.04ul LIPOFECTAMINE LTX,室温放置5分钟后加入500ul DMEM(+10%FBS)培养基和16万HEK293T细胞的24孔板中进行转染。12h后换成含1%双抗的新鲜培养基。继续培养60h后收细胞。
基因组DNA抽提和PCR扩增:
利用QuickExtractTM试剂按照试剂操作说明抽提转染后HEK293T细胞的基因组DNA,将抽提得到的基因组DNA利用以下引物29和引物30进行PCR扩增,并利用DNA胶回收试剂按照试剂操作说明对PCR产物进行切胶回收,用于DNA sanger测序。
表10
扩增基因组DNA使用PCR体系如下:HS DNA Polymerase(TAKARA)0.5μl;5×buffer 10μl;dNTPs 4μl;Forward Primer(10μM)1μl;Reverse Primer(10μM)1μl;Template 1ul;RNase-free water补至50μl。PCR程序如下:3min 94℃;32x(15sec 98℃,30sec 58℃,45s 72℃);7min 72℃。
DNA sanger测序:同实施例1。测序结果具体如图11和图12所示(两次重复实验数据)。
EditR分析sanger测序结果:同实施例1。。分析结果如图5和图6所示。
综上所述,本发明有效克服了现有技术中的种种缺点而具高度产业利用价值。
上述实施例仅例示性说明本发明的原理及其功效,而非用于限制本发明。任何熟悉此技术的人士皆可在不违背本发明的精神及范畴下,对上述实施例进行修饰或改变。因此,举凡所属技术领域中具有通常知识者在未脱离本发明所揭示的精神与技术思想下所完成的一切等效修饰或改变,仍应由本发明的权利要求所涵盖。
序列表
<110> 上海科技大学
<120> 一种碱基编辑分子及其用途
<160> 58
<170> SIPOSequenceListing 1.0
<210> 1
<211> 59
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 1
ggagagccgc caccatgccc aagaagaaga ggaaagtcat ggaagccagc ccagcatcc 59
<210> 2
<211> 64
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 2
gtgtggcgga ctctgaggtc ccgggagtct cgctgccgct gtttccctga ttctggagaa 60
tggc 64
<210> 3
<211> 44
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 3
cttggttcat ctcctacagc ccctgcttct cctggggctg tgcc 44
<210> 4
<211> 44
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 4
ggagaagcag gggctgtagg agatgaacca agtgaccctg taga 44
<210> 5
<211> 53
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 5
cctggagccc ctgcttctcc gcgggctgtg ccggggaagt gcgtgcgttc ctt 53
<210> 6
<211> 54
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 6
cgcacttccc cggcacagcc cgcggagaag caggggctcc aggagatgaa ccaa 54
<210> 7
<211> 44
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 7
atctatgatt acgactacct atataaggag gcactgcaaa tgct 44
<210> 8
<211> 44
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 8
tgcctcctta tataggtagt cgtaatcata gatgcgggca gcga 44
<210> 9
<211> 53
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 9
cttggttcat ctcctacagc ccctgcttct ccgcgggctg tgccggggaa gtg 53
<210> 10
<211> 44
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 10
ggagaagcag gggctgtagg agatgaacca agtgaccctg taga 44
<210> 11
<211> 41
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 11
ctgcccgcat ctttgattac gaccccctat ataaggaggc a 41
<210> 12
<211> 41
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 12
ggggtcgtaa tcaaagatgc gggcagcgaa gatacgcagt c 41
<210> 13
<211> 41
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 13
gcatctatga tgatgacccc ctatataagg aggcactgca a 41
<210> 14
<211> 44
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 14
tatagggggt catcatcata gatgcgggca gcgaagatac gcag 44
<210> 15
<211> 46
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 15
gctgcccgca tcttcgatta cgactaccta tataaggagg cactgc 46
<210> 16
<211> 45
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 16
ccttatatag gtagtcgtaa tcgaagatgc gggcagcgaa gatac 45
<210> 17
<211> 46
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 17
gcccgcatct atgatgacga ctacctatat aaggaggcac tgcaaa 46
<210> 18
<211> 44
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 18
ctccttatat aggtagtcgt catcatagat gcgggcagcg aaga 44
<210> 19
<211> 27
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 19
agatgaagca catcaaggac attctaa 27
<210> 20
<211> 27
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 20
aaaattagaa tgtccttgat gtgcttc 27
<210> 21
<211> 20
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 21
cccaaaaagg tagaaacaaa 20
<210> 22
<211> 22
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 22
aaactcatcc aaagagtatc tg 22
<210> 23
<211> 27
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 23
agatccctcg tcccccctgt gagtacc 27
<210> 24
<211> 27
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 24
aaaaggtact cacagggggg acgaggg 27
<210> 25
<211> 22
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 25
cgataaaatc aggaacttgt gc 22
<210> 26
<211> 20
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 26
aataactgtt caggccccac 20
<210> 27
<211> 27
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 27
agatttctcc cctctgctgg atacctc 27
<210> 28
<211> 27
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 28
aaaagaggta tccagcagag gggagaa 27
<210> 29
<211> 20
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 29
ctttgggcct cataaacaac 20
<210> 30
<211> 20
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 30
ggtgaaacaa gctgccattt 20
<210> 31
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 31
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Trp Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Tyr Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 32
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 32
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Tyr Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Tyr Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 33
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 33
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Tyr Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 34
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 34
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Trp Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Tyr Asp Tyr Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 35
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 35
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Tyr Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Tyr Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 36
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 36
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Tyr Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Tyr Asp Tyr Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 37
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 37
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Tyr Asp Tyr Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 38
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 38
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Tyr Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Phe Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 39
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 39
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Tyr Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Tyr Asp Asp Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 40
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 40
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Phe Asp Tyr Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 41
<211> 199
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 41
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His
1 5 10 15
Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr
20 25 30
Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met
35 40 45
Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys
50 55 60
Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro
65 70 75 80
Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile
85 90 95
Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala
100 105 110
Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg
115 120 125
Ile Tyr Asp Asp Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg
130 135 140
Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His
145 150 155 160
Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp
165 170 175
Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala
180 185 190
Ile Leu Gln Asn Gln Gly Asn
195
<210> 42
<211> 181
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 42
Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Lys Thr Tyr Leu Cys
1 5 10 15
Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met Asp Gln
20 25 30
His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe
35 40 45
Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro Ser Leu
50 55 60
Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp
65 70 75 80
Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala Phe Leu
85 90 95
Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr
100 105 110
Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg Asp Ala
115 120 125
Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His Cys Trp
130 135 140
Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly
145 150 155 160
Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu
165 170 175
Gln Asn Gln Gly Asn
180
<210> 43
<211> 1230
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 43
Met Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr
1 5 10 15
Leu Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp
20 25 30
Asn Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys
35 40 45
Gly Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp
50 55 60
Val Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu
65 70 75 80
Phe Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn
85 90 95
Leu Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn
100 105 110
Glu Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu
115 120 125
Pro Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe
130 135 140
Asn Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn
145 150 155 160
Met Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile
165 170 175
Asn Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys
180 185 190
Val Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys
195 200 205
Ile Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe
210 215 220
Phe Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile
225 230 235 240
Ile Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn
245 250 255
Glu Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys
260 265 270
Phe Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser
275 280 285
Phe Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe
290 295 300
Arg Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys
305 310 315 320
Leu Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile
325 330 335
Phe Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe
340 345 350
Gly Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp
355 360 365
Ile His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp
370 375 380
Arg Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu
385 390 395 400
Gln Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu
405 410 415
Ile Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser
420 425 430
Glu Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys
435 440 445
Asn Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys
450 455 460
Ser Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr
465 470 475 480
Asn Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile
485 490 495
Leu Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr
500 505 510
Gln Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro
515 520 525
Gln Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala
530 535 540
Thr Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys
545 550 555 560
Lys Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly
565 570 575
Asn Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met
580 585 590
Leu Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro
595 600 605
Ser Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly
610 615 620
Asp Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys
625 630 635 640
Asp Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn
645 650 655
Phe Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu
660 665 670
Val Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys
675 680 685
Glu Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile
690 695 700
Tyr Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His
705 710 715 720
Thr Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile
725 730 735
Arg Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys
740 745 750
Lys Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys
755 760 765
Asn Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr
770 775 780
Lys Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile
785 790 795 800
Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val
805 810 815
Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala
820 825 830
Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly
835 840 845
Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn
850 855 860
Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu
865 870 875 880
Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile
885 890 895
Lys Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys
900 905 910
Glu Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn
915 920 925
Ser Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln
930 935 940
Lys Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys
945 950 955 960
Lys Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile
965 970 975
Thr Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe
980 985 990
Ile Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr
995 1000 1005
Gly Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser
1010 1015 1020
Lys Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu
1025 1030 1035 1040
Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp
1045 1050 1055
Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile
1060 1065 1070
Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu
1075 1080 1085
Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile
1090 1095 1100
Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp
1105 1110 1115 1120
Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln
1125 1130 1135
Met Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser
1140 1145 1150
Pro Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu
1155 1160 1165
Ala Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala
1170 1175 1180
Tyr Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys
1185 1190 1195 1200
Ala Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys
1205 1210 1215
Glu Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser
1220 1225 1230
<210> 44
<211> 1307
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 44
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 Asn
1010 1015 1020
Cys Leu Val Leu Lys Asp Tyr Pro Ala Glu Lys Val Gly Gly Val Leu
1025 1030 1035 1040
Asn Pro Tyr Gln Leu Thr Asp Gln Phe Thr Ser Phe Ala Lys Met Gly
1045 1050 1055
Thr Gln Ser Gly Phe Leu Phe Tyr Val Pro Ala Pro Tyr Thr Ser Lys
1060 1065 1070
Ile Asp Pro Leu Thr Gly Phe Val Asp Pro Phe Val Trp Lys Thr Ile
1075 1080 1085
Lys Asn His Glu Ser Arg Lys His Phe Leu Glu Gly Phe Asp Phe Leu
1090 1095 1100
His Tyr Asp Val Lys Thr Gly Asp Phe Ile Leu His Phe Lys Met Asn
1105 1110 1115 1120
Arg Asn Leu Ser Phe Gln Arg Gly Leu Pro Gly Phe Met Pro Ala Trp
1125 1130 1135
Asp Ile Val Phe Glu Lys Asn Glu Thr Gln Phe Asp Ala Lys Gly Thr
1140 1145 1150
Pro Phe Ile Ala Gly Lys Arg Ile Val Pro Val Ile Glu Asn His Arg
1155 1160 1165
Phe Thr Gly Arg Tyr Arg Asp Leu Tyr Pro Ala Asn Glu Leu Ile Ala
1170 1175 1180
Leu Leu Glu Glu Lys Gly Ile Val Phe Arg Asp Gly Ser Asn Ile Leu
1185 1190 1195 1200
Pro Lys Leu Leu Glu Asn Asp Asp Ser His Ala Ile Asp Thr Met Val
1205 1210 1215
Ala Leu Ile Arg Ser Val Leu Gln Met Arg Asn Ser Asn Ala Ala Thr
1220 1225 1230
Gly 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 Ala
1250 1255 1260
Asn Gly Ala Tyr His Ile Ala Leu Lys Gly Gln Leu Leu Leu Asn His
1265 1270 1275 1280
Leu Lys Glu Ser Lys Asp Leu Lys Leu Gln Asn Gly Ile Ser Asn Gln
1285 1290 1295
Asp Trp Leu Ala Tyr Ile Gln Glu Leu Arg Asn
1300 1305
<210> 45
<211> 1300
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 45
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 Tyr
1010 1015 1020
Gln Lys Leu Glu Lys Met Leu Ile Glu Lys Leu Asn Tyr Leu Val Phe
1025 1030 1035 1040
Lys Asp Asn Glu Phe Asp Lys Thr Gly Gly Val Leu Arg Ala Tyr Gln
1045 1050 1055
Leu Thr Ala Pro Phe Glu Thr Phe Lys Lys Met Gly Lys Gln Thr Gly
1060 1065 1070
Ile Ile Tyr Tyr Val Pro Ala Gly Phe Thr Ser Lys Ile Cys Pro Val
1075 1080 1085
Thr Gly Phe Val Asn Gln Leu Tyr Pro Lys Tyr Glu Ser Val Ser Lys
1090 1095 1100
Ser Gln Glu Phe Phe Ser Lys Phe Asp Lys Ile Cys Tyr Asn Leu Asp
1105 1110 1115 1120
Lys Gly Tyr Phe Glu Phe Ser Phe Asp Tyr Lys Asn Phe Gly Asp Lys
1125 1130 1135
Ala Ala Lys Gly Lys Trp Thr Ile Ala Ser Phe Gly Ser Arg Leu Ile
1140 1145 1150
Asn Phe Arg Asn Ser Asp Lys Asn His Asn Trp Asp Thr Arg Glu Val
1155 1160 1165
Tyr Pro Thr Lys Glu Leu Glu Lys Leu Leu Lys Asp Tyr Ser Ile Glu
1170 1175 1180
Tyr Gly His Gly Glu Cys Ile Lys Ala Ala Ile Cys Gly Glu Ser Asp
1185 1190 1195 1200
Lys Lys Phe Phe Ala Lys Leu Thr Ser Val Leu Asn Thr Ile Leu Gln
1205 1210 1215
Met Arg Asn Ser Lys Thr Gly Thr Glu Leu Asp Tyr Leu Ile Ser Pro
1220 1225 1230
Val 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 Leu
1250 1255 1260
Lys Gly Leu Met Leu Leu Gly Arg Ile Lys Asn Asn Gln Glu Gly Lys
1265 1270 1275 1280
Lys Leu Asn Leu Val Ile Lys Asn Glu Glu Tyr Phe Glu Phe Val Gln
1285 1290 1295
Asn Arg Asn Asn
1300
<210> 46
<211> 83
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 46
Thr Asn Leu Ser Asp Ile Ile Glu Lys Glu Thr Gly Lys Gln Leu Val
1 5 10 15
Ile Gln Glu Ser Ile Leu Met Leu Pro Glu Glu Val Glu Glu Val Ile
20 25 30
Gly Asn Lys Pro Glu Ser Asp Ile Leu Val His Thr Ala Tyr Asp Glu
35 40 45
Ser Thr Asp Glu Asn Val Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr
50 55 60
Lys Pro Trp Ala Leu Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile
65 70 75 80
Lys Met Leu
<210> 47
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 47
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Trp
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Pro Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 48
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 48
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Trp
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Pro Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 49
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 49
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Ala
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Pro Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 50
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 50
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Trp
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Tyr Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 51
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 51
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Ala
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Pro Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 52
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 52
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Trp
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Tyr Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 53
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 53
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Ala
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Tyr Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 54
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 54
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Ala
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Phe Asp Tyr Asp Pro Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 55
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 55
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Ala
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Asp Asp Pro Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 56
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 56
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Ala
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Phe Asp Tyr Asp Tyr Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 57
<211> 1558
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 57
Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly
1 5 10 15
Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn
20 25 30
Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu
35 40 45
Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His
50 55 60
Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu
65 70 75 80
Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln
85 90 95
Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Ala
100 105 110
Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val
115 120 125
Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Asp Asp Tyr Leu Tyr
130 135 140
Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile
145 150 155 160
Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His
165 170 175
Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln
180 185 190
Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser
195 200 205
Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met
210 215 220
Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu
225 230 235 240
Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn
245 250 255
Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly
260 265 270
Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val
275 280 285
Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe
290 295 300
Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu
305 310 315 320
Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu
325 330 335
Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro
340 345 350
Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn
355 360 365
Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met
370 375 380
Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn
385 390 395 400
Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val
405 410 415
Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile
420 425 430
Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe
435 440 445
Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile
450 455 460
Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu
465 470 475 480
Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe
485 490 495
Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe
500 505 510
Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg
515 520 525
Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu
530 535 540
Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe
545 550 555 560
Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly
565 570 575
Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile
580 585 590
His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg
595 600 605
Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln
610 615 620
Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile
625 630 635 640
Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu
645 650 655
Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn
660 665 670
Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser
675 680 685
Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn
690 695 700
Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu
705 710 715 720
Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln
725 730 735
Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln
740 745 750
Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr
755 760 765
Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys
770 775 780
Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn
785 790 795 800
Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu
805 810 815
Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser
820 825 830
Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp
835 840 845
Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp
850 855 860
Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe
865 870 875 880
Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val
885 890 895
Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu
900 905 910
Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr
915 920 925
Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr
930 935 940
Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg
945 950 955 960
Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys
965 970 975
Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn
980 985 990
Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys
995 1000 1005
Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile Ala
1010 1015 1020
Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val Arg
1025 1030 1035 1040
Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala Arg
1045 1050 1055
Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly Asn
1060 1065 1070
Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn Gly
1075 1080 1085
Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu Lys
1090 1095 1100
Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile Lys
1105 1110 1115 1120
Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu
1125 1130 1135
Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn Ser
1140 1145 1150
Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys
1155 1160 1165
Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys
1170 1175 1180
Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr
1185 1190 1195 1200
Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile
1205 1210 1215
Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly
1220 1225 1230
Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys
1235 1240 1245
Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu Asp
1250 1255 1260
Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr Asp Ala
1265 1270 1275 1280
Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn Arg Ile Arg
1285 1290 1295
Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp Trp Glu Glu Val
1300 1305 1310
Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn Lys Tyr Gly Ile Asn
1315 1320 1325
Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu Cys Glu Gln Ser Asp Lys
1330 1335 1340
Ala Phe Tyr Ser Ser Phe Met Ala Leu Met Ser Leu Met Leu Gln Met
1345 1350 1355 1360
Arg Asn Ser Ile Thr Gly Arg Thr Asp Val Ala Phe Leu Ile Ser Pro
1365 1370 1375
Val Lys Asn Ser Asp Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala
1380 1385 1390
Gln Glu Asn Ala Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr
1395 1400 1405
Asn Ile Ala Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala
1410 1415 1420
Glu Asp Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu
1425 1430 1435 1440
Trp Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys
1445 1450 1455
Lys Arg Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu
1460 1465 1470
Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu
1475 1480 1485
Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp Ile
1490 1495 1500
Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val Met Leu
1505 1510 1515 1520
Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu Val Ile Gln
1525 1530 1535
Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser Gly Gly Ser Pro
1540 1545 1550
Lys Lys Lys Arg Lys Val
1555
<210> 58
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 58
Pro Lys Lys Lys Arg Lys Val
1 5
Claims (10)
1.一种碱基编辑分子,其特征在于,包括hA3A片段、dCas12a片段和UGI片段,所述碱基编辑分子的氨基酸序列如SEQ ID No. 48所示。
2.如权利要求1所述的碱基编辑分子,其特征在于,所述碱基编辑分子还包括NLS片段。
3.一种分离的多核苷酸,编码如权利要求1~2任一权利要求所述的碱基编辑分子。
4.一种碱基编辑体系,包括如权利要求1~2任一权利要求所述的碱基编辑分子以及sgRNA。
5.一种表达系统,所述表达系统包括能够表达如权利要求4所述的碱基编辑体系的宿主细胞。
6.如权利要求5所述的表达系统,其特征在于,所述宿主细胞选自真核细胞或原核细胞。
7.如权利要求1~2任一权利要求所述的碱基编辑分子、如权利要求3所述的多核苷酸、如权利要求4所述的碱基编辑体系或如权利要求5~6任一权利要求所述的表达系统在非疾病诊断或治疗目的的基因编辑中的用途。
8.如权利要求7所述的用途,其特征在于,所述用途具体为在真核生物的基因编辑中的用途。
9.一种非疾病诊断或治疗目的的基因编辑方法,包括:通过如权利要求1~2任一所述的碱基编辑分子或如权利要求4所述的碱基编辑体系进行基因编辑。
10.如权利要求9所述的基因编辑方法,其特征在于,所述基因编辑方法包括:在适当条件下培养如权利要求5~6任一权利要求所述的表达系统;
和/或,所述基因编辑方法为体外基因编辑方法。
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