CN114213547A - 一种展示新冠s蛋白的融合蛋白和重组病毒粒子及其应用 - Google Patents

一种展示新冠s蛋白的融合蛋白和重组病毒粒子及其应用 Download PDF

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CN114213547A
CN114213547A CN202111541851.3A CN202111541851A CN114213547A CN 114213547 A CN114213547 A CN 114213547A CN 202111541851 A CN202111541851 A CN 202111541851A CN 114213547 A CN114213547 A CN 114213547A
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陈瑞婷
孙慧敏
毛水花
周孟云
宋家升
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Zhejiang Difu Runsi Biotechnology Co ltd
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Abstract

本发明提供了一种展示新冠S蛋白的融合蛋白和重组病毒粒子及其应用，本发明属于生物制品技术领域。本发明提供了一种表达新冠S蛋白的融合基因及融合蛋白，该融合基因或融合蛋白包含新冠S蛋白的胞外结构域序列与禽副黏病毒科F蛋白的跨膜结构域和胞内结构域序列。同时，含有该序列的重组NDV病毒具有较强的中和抗体的能力。可见，S蛋白的胞外域编码序列和APMV病毒科病毒(除NDV外)F蛋白的跨膜结构域和胞内结构域编码序列相融合所产生的融合基因或蛋白，具有成为优秀新冠疫苗候选抗原的巨大潜力。

Description

一种展示新冠S蛋白的融合蛋白和重组病毒粒子及其应用
技术领域
本发明属于生物制品技术领域，具体涉及一种展示新冠S蛋白的融合蛋白以及重组病毒粒子及其应用。
背景技术
新冠病毒的免疫原性相对较弱，在以活病毒为载体构建疫苗株时，理想情况下，希望病毒粒子表面或被病毒感染进而表达细胞膜抗原的细胞表面有更多的抗原蛋白展示。新冠病毒的S蛋白是病毒与宿主细胞膜受体ACE2结合，进而感染宿主细胞的关键蛋白。S蛋白属于I型跨膜蛋白，其在细胞膜上的表达量与跨膜区氨基酸排列有关。以新城疫(NewcastleDisease virus,NDV)病毒新型冠状重组疫苗株为例，前期研究发现，将新型冠状病毒(SARS-COV-2)的S蛋白的跨膜结构域和胞内结构域更换为NDV F蛋白的跨膜结构域和胞内结构域后所拯救得到的重组NDV-COVS-F病毒，其免疫原性比原始S蛋白直接插入NDV病毒载体所形成的重组病毒更好。然而，将S蛋白的跨膜结构域和胞内结构域更换为NDV F蛋白的跨膜结构域和胞内结构域，有极大可能使得S蛋白的上膜与NDV病毒本身F蛋白的上膜形成竞争关系，干扰细胞膜上抗原蛋白的表达或者病毒组装，影响其免疫原性。
发明内容
有鉴于此，本发明的目的在于提供一种展示新冠S蛋白的融合蛋白和构建的相应重组病毒及其应用。
本发明提供了一种展示新冠病毒S蛋白的融合蛋白，包含新冠病毒S蛋白的胞外域序列和含禽副黏病毒科病毒F蛋白的跨膜结构域和胞内结构域的序列。
优选的，所述禽副黏病毒科病毒包括以下一种或几种血清型：APMV-2、APMV-3、APMV-4、APMV-5、APMV-6、APMV-7、APMV-8、APMV-9、APMV-10、APMV-11或APMV-12；
优选的，所述禽副黏病毒科病毒包括以下一种或几种血清型：APMV-3、APMV-5、APMV-7和APMV-8血清型。
优选的，所述新冠S蛋白的胞外结构域来源于新冠原始毒株或变异株。
优选的，所述新冠S蛋白的胞外结构域序列还包括以下一种或几种蛋白编码序列：S2P，S6P，S2P/GSAS；
所述S2P是将所述新冠S蛋白胞外域进行K986P和V987P突变所形成的蛋白编码序列；
所述S2P/GSAS蛋白编码序列是在S2P基础上将第682～685位氨基酸RRAR突变为GSAS所形成的蛋白编码序列；
所述S6P蛋白编码序列是在S2P基础上进行F817P、A892P、A899P和A942P突变所形成的蛋白编码序列。
本发明提供了一种编码所述融合蛋白的融合基因。
本发明提供了一种包含所述融合基因的重组病毒载体。
优选的，所述重组病毒载体以新城疫病毒载体为骨架载体。
优选的，所述融合基因以表达盒子形式插入新城疫病毒载体的P基因和M基因之间。
本发明提供了一种由所述重组病毒载体制备得到的重组病毒粒子或疫苗株。
本发明提供了所述融合蛋白、所述融合基因、所述重组病毒载体或所述重组病毒粒子或疫苗株在制备防控新冠肺炎的疫苗中的应用。
本发明提供的一种展示新冠病毒S蛋白的融合蛋白，包括新冠病毒S蛋白的胞外域序列和禽副黏病毒科F蛋白的跨膜结构域和胞内结构域编码序列。本发明采用禽副黏病毒科F蛋白的跨膜结构域和胞内结构域序列替换新冠病毒S蛋白的原始跨膜结构域和胞内结构域后形成的融合蛋白可以解决以下技术问题：1)避免融合蛋白的上膜与新城疫病毒F蛋白的上膜形成竞争关系；2)提高了融合蛋白或重组新城疫病毒免疫小鼠后产生中和抗体的能力，减弱了融合蛋白或重组新城疫病毒产生垃圾抗体的能力，极大地增强了免疫原性。可见，S蛋白的胞外域编码序列和APMV病毒科病毒(除NDV外)F蛋白的跨膜结构域和胞内结构域编码序列相融合所产生的融合基因或蛋白，具有成为优秀新冠疫苗候选抗原的巨大潜力。
进一步的，本发明具体限定了APMV病毒科病毒的种类，其中融合蛋白S2P-AP3(aa3)、S2P-AP5、S2P-AP7、S2P-AP8或其编码基因都具有优异的免疫原性，可用于防控新冠肺炎的疫苗的制备。
附图说明
图1为本发明提供的融合基因所表达蛋白示意图，其中ECD：胞外结构域；TM：跨膜结构域；CT：胞内结构域；
图2为本发明实施例中ELISA检测免疫血清S1 IgG相对含量；
图3为本发明实施例中假病毒中和试验，其中横坐标为血清稀释比，纵坐标为假病毒感染细胞后荧光百分比。
具体实施方式
本发明提供了一种展示新冠病毒S蛋白的融合蛋白，包含新冠病毒S蛋白的胞外域序列和禽副黏病毒科F蛋白的跨膜结构域和胞内结构域序列。所述融合蛋白示意图见图1。将新冠病毒S蛋白的胞外域与含禽副黏病毒科F蛋白的跨膜结构域和胞内结构域的序列相融合。
在本发明中，所述禽副黏病毒科优选包括血清型APMV-2、APMV-3、APMV-4、APMV-5、APMV-6、APMV-7、APMV-8、APMV-9、APMV-10、APMV-11或APMV-12，更优选为包括血清型APMV-3、APMV-5、APMV-7或APMV-8。其中各禽副黏病毒科F蛋白的来源及序列信息见表1。
表1各禽副黏病毒科F蛋白的来源及序列信息
Figure BDA0003414502590000021
Figure BDA0003414502590000031
其中，AP3(aa3)和AP3(aa33)的区别在于F蛋白跨膜结构域前截取了不同氨基酸数量，AP3(aa3)为F蛋白跨膜区前截取3个氨基酸(F蛋白的胞外区)，而AP3(aa3)F蛋白跨膜区前截取33个氨基酸序列(F蛋白的胞外区)。
在本发明中，所述新冠病毒S蛋白优选包括原始或变异株的新冠病毒S蛋白或在S蛋白的基础上发生S2P、S6P或S2P/GSAS突变的S蛋白。本发明实施例中，所述新冠病毒S蛋白来源于Delta新冠病毒株。所述新冠病毒S蛋白的来源及序列信息见表2。
表2 S蛋白的来源及序列信息
Figure BDA0003414502590000032
在本发明中，新冠病毒S蛋白的胞外域和禽副黏病毒科F蛋白的跨膜结构域和胞内结构域序列之间优选用linker连接肽连接。本发明对所述蛋白linker的序列没有特殊限制，采用本领域所熟知的蛋白linker即可。所述linker连接肽的氨基酸序列优选见SEQ IDNO:14(GGSGS)。
本发明提供了一种编码所述融合蛋白的融合基因。所述融合基因的序列见表3。
融合基因简称 对应氨基酸序列组成 序列编号
S2P-AP2(1) S2P序列+AP2(1)序列 SEQ ID NO:15
S2P-AP2(2) S2P序列+AP2(2)序列 SEQ ID NO:16
S2P-AP3(aa3) S2P序列+AP3(aa3)序列 SEQ ID NO:17
S2P-AP3(aa33) S2P序列+AP3(aa33)序列 SEQ ID NO:18
S2P-AP4 S2P序列+AP4序列 SEQ ID NO:19
S2P-AP5 S2P序列+AP5序列 SEQ ID NO:20
S2P-AP6 S2P序列+AP6序列 SEQ ID NO:21
S2P-AP7 S2P序列+AP7序列 SEQ ID NO:22
S2P-AP8 S2P序列+AP8序列 SEQ ID NO:23
在本发明中，所述融合基因经过密码子优化后，在5’端添加kozak序列(GCCACC)后进行基因合成。
本发明提供了一种含所述融合基因的重组病毒载体。所述重组病毒载体的骨架载体优选为NDV Lasota株载体。所述融合基因以表达盒子形式插入NDV病毒载体的P基因和M基因之间。
在本发明中，所述重组NDV病毒载体的构建方法，优选在所述融合基因的5’端和3'端分别添加转录终止信号(SEQ ID NO:24，TTAGAAAAAA)，转录起始信号(SEQ ID NO:25，ACGGGTAGAA)，通过同源重组方式克隆至骨架载体中，形成重组病毒载体。
本发明提供了一种由所述重组病毒载体制备的重组病毒粒子或疫苗株。
在本发明中，将表达融合蛋白的质粒采用肌肉注射，重组病毒粒子或疫苗株以鼻腔滴注方式免疫动物，检测血清结合抗体含量以及对假病毒的中和能力。结果显示，1)不同血清型病毒来源的F蛋白的跨膜区与胞内区可能间接影响融合蛋白的免疫原性发挥，与S2P蛋白相比，禽副黏病毒科F蛋白的跨膜结构域和胞内结构域序列的替换能够提高重组新城疫病毒中和抗体活性；
2)同一种血清型下的两株病毒，其质粒免疫产生的抗体水平并不一致，例如APMV-2的两种不同的病毒株来源的F蛋白的跨膜结构域和胞内结构域序列，质粒免疫拥有不同的结合抗体产生能力；
3)质粒免疫时pS2P-AP3(aa3)、pS2P-AP7、pS2P-AP5、pS2P-AP8结合抗体产生能力不及pS2P，但血清中和抗体能力更加强劲。重组病毒免疫时，NDV-S2P-AP7与NDV-S2P结合抗体水平相当，但血清中和抗体表现更优异，可见，本发明所形成的融合蛋白或重组新城疫病毒免疫小鼠所产生抗体中，有更高的比例的病毒中和抗体，为日后形成疫苗和多次免疫时降低抗体依赖增强效应的发生奠定基础。
基于所述融合蛋白具有优异的免疫原性，本发明提供了所述重组病毒载体或所述重组病毒粒子或疫苗株在制备防控新冠肺炎的疫苗中的应用。
本发明对所述疫苗的制备方法没有特殊限制，采用本领域所熟知的疫苗制备方法即可。所述疫苗具有较强的中和抗体能力，因此，在防控新冠肺炎中具有较高的应用价值。所述疫苗优选包括所述重组病毒粒子或疫苗株和佐剂。
下面结合实施例对本发明提供的一种展示新冠S蛋白的融合蛋白和重组病毒及其应用进行详细的说明，但是不能把它们理解为对本发明保护范围的限定。
实施例1
1.融合基因设计及合成
对新冠病毒(新冠Delta变异株)的S蛋白的胞外域编码序列(氨基酸1-1213，SEQID NO:17)进行K986P和V987P位突变后，分别融合APMV-2、APMV-3、APMV-4、APMV-5/APMV-6、APMV-7、APMV-8血清型病毒种病毒F蛋白的C端包含跨膜结构域和胞内结构域部分的编码序列。在S2P蛋白和F蛋白C端包含跨膜结构域和胞内结构域部分的编码序列之间添加蛋白linker。因APMV病毒科除NDV外，其他病毒株的F蛋白都未收录进入Swiss-Prot数据库中，所以使用跨膜区域预测软件TMHMM-2.0对APMV病毒科APMV-2、APMV-3、APMV-4、APMV-5、APMV-6、APMV-7、APMV-8的选中病毒株进行F蛋白的跨膜结构域预测。需要指出的是，不同蛋白结构预测软件得到的跨膜结构域和胞内结构域可能存在几个氨基酸的偏差，这些都属于我们的保护范围。其中，APMV-2F基因来自于APMV-2/Procarduelis nipalensis/China/Suiling/53/2013病毒株或APMV-2/Chicken/England/7702/06病毒株基因组，分别形成S2P-AP2(1)和S2P-AP2(2)融合基因序列；APMV-3F基因来自于APMV3/PKT/Netherland/449/75病毒株基因组，分别设计形成S2P-AP3(aa3)和S2P-AP3(aa33)融合基因序列；APMV-4F基因来自于APMV-4/White-Fronted Goose/Syvaske/Ukraine/6-15-03/2014病毒株基因组，设计形成S2P-AP4融合基因序列(SEQ ID NO:23)；APMV-5F基因来自于Avianparamyxovirus 5strain Budgerigar/Kunitachi/74病毒株基因组，设计形成S2P-AP5融合基因序列；APMV-6F基因来自于Avian paramyxovirus 6isolate teal/Novosibirskregion/455/2009病毒株基因组，设计形成S2P-AP6融合基因序列；APMV-7F基因来自于APMV-7/dove/Tennessee/4/75病毒株基因组，设计形成S2P-AP7融合基因序列；APMV-8F基因来自于Avian paramyxovirus 8strain goose/Delaware/1053/76病毒株基因组，设计形成S2P-AP8融合基因序列。
以上所设计形成的融合基因序列经过密码子优化后，在5’端添加kozak序列(GCCACC)通过金唯智生物进行基因合成，并克隆到pcDNA3.1(+)载体的EcoRI和XhoI限制性酶切位点之间。分别形成pS2P-AP2(1)，pS2P-AP2(2)，pS2P-AP3(aa3)，pS2P-AP3(aa33)，pS2P-AP4，pS2P-AP5，pS2P-AP6，pS2P-AP7和pS2P-AP8表达质粒。
实施例2
重组NDV病毒载体的构建及重组NDV病毒拯救
在实施例1设计得到的融合基因序列的3'端分别添加转录终止信号(TTAGAAAAAA，SEQ ID NO:24)，在5’端添加转录起始信号(ACGGGTAGAA,，SEQ ID NO:25)，设计引物扩增含有转录起始信号和转录终止信号的融合基因序列，通过同源重组的方式克隆进入NDVLasota株载体的P基因和M基因位置之间，构建得到一系列重组NDV病毒载体。
将上述构建的重组NDV病毒载体和病毒拯救辅助质粒pCI-NP、pCI-P和pCI-L以1：1：1：1比例，经Nano drop测定质粒浓度后，转染BHK21-T7细胞。转染后72h，反复冻融细胞3次，并将混合物接种9～11日龄SPF鸡胚，0.2～0.3mL/胚，37℃培养24h。弃去24h内的死胚，收获72h内存活的鸡胚尿囊液并测量血凝价。将有血凝价(达到2log及以上)且存活的鸡胚尿囊液离心后分装，冻存于-80℃冰箱，同时根据HiScript III 1st Strand cDNASynthesis Kit试剂盒说明书要求对提取的RNA进行反转录，合成首链cDNA。之后对合成的cDNA进行PCR凝胶电泳鉴定，PCR反应体系和反应条件按照喏唯赞HiscriptII One StepRT-PCR kit说明书要求设置。鉴定上游引物NDV-F3153：AAGGTCCAACTCTCCAAGCGG(SEQ IDNO:26)，下游引物NDV-R3454：GTCCTCCTTACTATCAGTCCACA(SEQ ID NO:27)。最终形成的重组NDV病毒疫苗株命名为NDV-S2P-AP3(aa3)和NDV-S2P-AP7。
对比例1
将S2P蛋白的跨膜域和胞内域序列与含NDV病毒F蛋白跨膜域和胞内域的序列相融合，得到融合蛋白(SEQ ID NO:28)，按照实施例1的方法合成编码融合蛋白的融合基因(SEQID NO:29)，按照实施例2的方法构建重组载体以及拯救病毒，最终得到的重组新城疫病毒粒子命名为NDV-S2P/F34。
实施例3
小鼠免疫试验
分别使用实施例2构建的含融合基因的质粒和重组NDV病毒对4-5周龄Babl/c小鼠进行免疫，每种质粒或重组病毒分别免疫四只小鼠。质粒免疫程序为肌肉注射100μg/只(可补加无菌PBS，最终注射体积不低于100μL/只)，免疫后10天采血。重组NDV病毒免疫程序为滴鼻50μL/只，分别在第0天和第7天进行免疫，第14天采血，免疫时重组病毒血凝价为6～7log2。对照组采用无菌PBS进行免疫。
实施例4
ELISA检测免疫血清新冠S蛋白结合抗体
提前将96孔酶标板放置室温平衡，使用义翘神州(SARS-CoV-2(2019-nCoV)SpikeS1抗体滴度检测试剂盒中稀释液对样本血清及阳性对照分别做20倍稀释。按照检测试剂盒说明书要求进行洗板、样本孵育、抗体孵育、显色和终止反应，最后在酶标仪下读取OD450数值。分别以每个样品的OD450读数除以背景OD450读数即得到相对IgG抗体数据。
结果如图2所示。可见，免疫小鼠后，含有融合基因S2P-AP3(aa3)、S2P-AP5、S2P-AP7、S2P-AP8的质粒和重组NDV病毒NDV-S2P-AP3(aa3),NDV-S2P-AP7结合抗体相对较高。特别是NDV-S2P-AP3(aa3)，其抗体水平达到NDV-S2P的大约7倍之多。然而，并非质粒的结合抗体高，所形成的重组NDV病毒其结合抗体就高，这可能与病毒出芽及包装机制有关。同时，从实验结果可以发现，对于APMV-2，即同一种血清型下的两株病毒，其产生的抗体水平并不一样，可见，S蛋白胞外域融合某一毒株F蛋白的跨膜结构域和胞内结构域所形成的融合蛋白，免疫结果并不能反应所有该血清型下的其他病毒株的免疫效果，鉴于APMV病毒科囊括的病毒株太多，这里仍然有广阔的深入发掘研究空间。另外，pS2P-AP3(aa3)和pS2P-AP3(aa33)的免疫效果差异较大，这两种融合基因所表达蛋白的跨膜结构域和胞内结构域氨基酸序列一致，不同的是，在跨膜结构域之前所选择的延伸区段长度不同。我们推测，出现这一结果的原因很可能是由于跨膜结构域之前所选择的延伸区段影响了整个融合蛋白的构象。
实施例5
假病毒中和试验
取15μL待测血清加入96孔板，加入135μL DMEM培养基进行稀释。随后进行4个梯度的2倍比稀释。在稀释后的血清中加入50μL假病毒液37℃孵育1h，假病毒使用VSV-S△24-GFP(Xiong HL,Wu YT,Cao JL,et al.Robust neutralization assay based on SARS-CoV-2S-protein-bearing vesicular stomatitis virus(VSV)pseudovirus and ACE2-overexpressing BHK21 cells.Emerg Microbes Infect.2020；9(1):2105-2113.doi:10.1080/22221751.2020.1815589)是由VSV病毒载体G囊膜蛋白删除后插入新冠S△24基因以及GFP基因经病毒拯救而来，S△24基因删除了新冠S蛋白C端的24个氨基酸，使得S蛋白可以更多地呈现在VSV病毒囊膜上。孵育30min时，消化Vero-E6细胞，孵育结束后，每孔加入100μL细胞，37℃，5％CO2细胞培养箱中培养24h。同时设置无血清细胞对照(150μL MEDM培养基+100μL细胞)和无血清病毒对照(100μL MEDM培养基+50μL假病毒+100μL细胞)。最后在荧光显微镜下拍照，记录每孔细胞荧光百分比数。
结果见图3和表4。
表4重组质粒和重组NDV病毒中和试验结果
Figure BDA0003414502590000061
由图3可见，质粒pS2P-AP3(aa3)、pS2P-AP8、pS2P-AP5、pS2P-AP7以及NDV-S2P-AP7免疫小鼠后，血清中和抗体水平均高于pS2P或NDV-S2P免疫后小鼠。
优秀的抗原应该能产生出更多的中和抗体，以及尽量少的非中和活性的抗体。综合本发明的结合抗体以及假病毒中和抗体试验结果可以发现，在质粒免疫时，融合基因S2P-AP3(aa3)、S2P-AP5以及S2P-AP7相对于S2P基因产生结合抗体的程度稍弱，但产生中和抗体的能力更强。由于本发明在进行重组病毒的拯救过程中，选择了质粒免疫结果相对较好的融合基因进行测试，但这不能排除其他质粒免疫效果一般的融合基因不能得到类似优良的免疫效果。由此得出，S蛋白的胞外域编码序列和APMV病毒科病毒(除NDV外)F蛋白的跨膜结构域和胞内结构域编码序列相融合所产生的融合基因或蛋白，具有成为优秀新冠疫苗候选抗原的巨大潜力。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
序列表
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Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu
210 215 220
Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu
225 230 235 240
Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp
245 250 255
Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr
260 265 270
Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp
275 280 285
Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe
290 295 300
Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro
305 310 315 320
Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe
325 330 335
Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn
340 345 350
Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn
355 360 365
Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys
370 375 380
Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile
385 390 395 400
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
405 410 415
Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile
420 425 430
Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn
435 440 445
Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg
450 455 460
Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly
465 470 475 480
Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln
485 490 495
Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser
500 505 510
Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser
515 520 525
Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu
530 535 540
Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe
545 550 555 560
Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp
565 570 575
Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly
580 585 590
Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val
595 600 605
Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala
610 615 620
Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val
625 630 635 640
Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn
645 650 655
Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr
660 665 670
Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln
675 680 685
Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala
690 695 700
Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val
705 710 715 720
Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys
725 730 735
Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu
740 745 750
Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile
755 760 765
Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys
770 775 780
Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe
785 790 795 800
Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile
805 810 815
Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile
820 825 830
Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile
835 840 845
Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr
850 855 860
Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile
865 870 875 880
Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe
885 890 895
Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn
900 905 910
Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala
915 920 925
Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly
930 935 940
Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu
945 950 955 960
Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn
965 970 975
Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp
980 985 990
Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln
995 1000 1005
Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala
1010 1015 1020
Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe
1025 1030 1035 1040
Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1045 1050 1055
Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn
1060 1065 1070
Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro
1075 1080 1085
Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln
1090 1095 1100
Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val
1105 1110 1115 1120
Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr
1125 1130 1135
Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys
1140 1145 1150
Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser
1155 1160 1165
Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu
1170 1175 1180
Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu
1185 1190 1195 1200
Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro
1205 1210
<210> 11
<211> 1211
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 11
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser
145 150 155 160
Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp
165 170 175
Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe
180 185 190
Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile
195 200 205
Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu
210 215 220
Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu
225 230 235 240
Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp
245 250 255
Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr
260 265 270
Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp
275 280 285
Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe
290 295 300
Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro
305 310 315 320
Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe
325 330 335
Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn
340 345 350
Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn
355 360 365
Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys
370 375 380
Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile
385 390 395 400
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
405 410 415
Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile
420 425 430
Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn
435 440 445
Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg
450 455 460
Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly
465 470 475 480
Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln
485 490 495
Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser
500 505 510
Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser
515 520 525
Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu
530 535 540
Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe
545 550 555 560
Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp
565 570 575
Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly
580 585 590
Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val
595 600 605
Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala
610 615 620
Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val
625 630 635 640
Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn
645 650 655
Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr
660 665 670
Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln
675 680 685
Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala
690 695 700
Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val
705 710 715 720
Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys
725 730 735
Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu
740 745 750
Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile
755 760 765
Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys
770 775 780
Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe
785 790 795 800
Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Pro Ile
805 810 815
Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile
820 825 830
Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile
835 840 845
Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr
850 855 860
Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile
865 870 875 880
Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala Leu Gln Ile Pro Phe
885 890 895
Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn
900 905 910
Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala
915 920 925
Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Pro Ser Ala Leu Gly
930 935 940
Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu
945 950 955 960
Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn
965 970 975
Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp
980 985 990
Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln
995 1000 1005
Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala
1010 1015 1020
Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe
1025 1030 1035 1040
Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1045 1050 1055
Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn
1060 1065 1070
Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro
1075 1080 1085
Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln
1090 1095 1100
Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val
1105 1110 1115 1120
Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr
1125 1130 1135
Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys
1140 1145 1150
Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser
1155 1160 1165
Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu
1170 1175 1180
Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu
1185 1190 1195 1200
Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro
1205 1210
<210> 12
<211> 1211
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 12
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser
145 150 155 160
Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp
165 170 175
Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe
180 185 190
Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile
195 200 205
Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu
210 215 220
Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu
225 230 235 240
Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp
245 250 255
Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr
260 265 270
Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp
275 280 285
Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe
290 295 300
Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro
305 310 315 320
Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe
325 330 335
Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn
340 345 350
Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn
355 360 365
Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys
370 375 380
Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile
385 390 395 400
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
405 410 415
Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile
420 425 430
Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn
435 440 445
Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg
450 455 460
Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly
465 470 475 480
Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln
485 490 495
Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser
500 505 510
Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser
515 520 525
Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu
530 535 540
Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe
545 550 555 560
Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp
565 570 575
Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly
580 585 590
Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val
595 600 605
Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala
610 615 620
Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val
625 630 635 640
Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn
645 650 655
Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr
660 665 670
Gln Thr Gln Thr Asn Ser Arg Gly Ser Ala Ser Ser Val Ala Ser Gln
675 680 685
Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala
690 695 700
Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val
705 710 715 720
Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys
725 730 735
Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu
740 745 750
Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile
755 760 765
Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys
770 775 780
Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe
785 790 795 800
Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile
805 810 815
Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile
820 825 830
Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile
835 840 845
Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr
850 855 860
Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile
865 870 875 880
Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe
885 890 895
Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn
900 905 910
Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala
915 920 925
Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly
930 935 940
Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu
945 950 955 960
Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn
965 970 975
Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp
980 985 990
Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln
995 1000 1005
Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala
1010 1015 1020
Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe
1025 1030 1035 1040
Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1045 1050 1055
Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn
1060 1065 1070
Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro
1075 1080 1085
Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln
1090 1095 1100
Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val
1105 1110 1115 1120
Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr
1125 1130 1135
Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys
1140 1145 1150
Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser
1155 1160 1165
Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu
1170 1175 1180
Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu
1185 1190 1195 1200
Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro
1205 1210
<210> 13
<211> 1211
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 13
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser
145 150 155 160
Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp
165 170 175
Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe
180 185 190
Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile
195 200 205
Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu
210 215 220
Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu
225 230 235 240
Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp
245 250 255
Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr
260 265 270
Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp
275 280 285
Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe
290 295 300
Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro
305 310 315 320
Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe
325 330 335
Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn
340 345 350
Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn
355 360 365
Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys
370 375 380
Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile
385 390 395 400
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
405 410 415
Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile
420 425 430
Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn
435 440 445
Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg
450 455 460
Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly
465 470 475 480
Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln
485 490 495
Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser
500 505 510
Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser
515 520 525
Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu
530 535 540
Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe
545 550 555 560
Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp
565 570 575
Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly
580 585 590
Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val
595 600 605
Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala
610 615 620
Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val
625 630 635 640
Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn
645 650 655
Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr
660 665 670
Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln
675 680 685
Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala
690 695 700
Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val
705 710 715 720
Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys
725 730 735
Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu
740 745 750
Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile
755 760 765
Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys
770 775 780
Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe
785 790 795 800
Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile
805 810 815
Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile
820 825 830
Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile
835 840 845
Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr
850 855 860
Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile
865 870 875 880
Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe
885 890 895
Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn
900 905 910
Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala
915 920 925
Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly
930 935 940
Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu
945 950 955 960
Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn
965 970 975
Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp
980 985 990
Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln
995 1000 1005
Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala
1010 1015 1020
Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe
1025 1030 1035 1040
Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1045 1050 1055
Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn
1060 1065 1070
Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro
1075 1080 1085
Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln
1090 1095 1100
Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val
1105 1110 1115 1120
Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr
1125 1130 1135
Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys
1140 1145 1150
Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser
1155 1160 1165
Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu
1170 1175 1180
Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu
1185 1190 1195 1200
Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro
1205 1210
<210> 14
<211> 5
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 14
Gly Gly Ser Gly Ser
1 5
<210> 15
<211> 3936
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 15
atgttcgtgt ttctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgcggacc 60
agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120
aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180
aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240
aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300
atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360
aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420
ctggacgtgt actatcacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480
gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540
cagggcaact tcaagaacct gcgcgagttc gtgttcaaga acatcgacgg ctacttcaag 600
atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660
ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720
gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780
gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840
ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900
ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960
accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020
aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080
gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140
tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200
cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260
tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320
tccaaagtcg gcggcaacta caattaccgg tacaggctgt tccggaagtc caatctgaag 1380
cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgcaacggc 1440
gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500
gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560
acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620
ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680
cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740
gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800
aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtacaga ggtgccagtg 1860
gccattcacg ccgatcagct gacccctact tggcgggtgt actccacagg cagcaatgtg 1920
tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980
gacatcccca tcggcgctgg catctgtgcc agctaccaga cacagaccaa cagcaggcgg 2040
agagccagat ctgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100
aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160
accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220
tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280
ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340
gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400
agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460
ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520
gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580
cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640
acaagcggct ggacatttgg agctggcgcc gctctgcaga tcccctttgc tatgcagatg 2700
gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760
atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820
agcgccctgg gaaagctgca gaacgtcgtg aaccagaacg cccaggcact gaacaccctg 2880
gtcaagcagc tgtcctccaa cttcggcgcc atctctagcg tgctgaacga tatcctgagc 2940
agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactccag 3000
tctctgcaga cctacgtgac ccagcagctg atcagagccg ccgagattag agccagcgct 3060
aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120
tgcggcaagg gctaccacct gatgagcttc cctcagtctg caccacacgg cgtggtgttt 3180
ctgcacgtga catacgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240
cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300
ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360
tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420
cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480
gacgtggacc tgggcgatat cagcggaatc aatgccagcg tggtcaacat ccagaaagag 3540
atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600
ctggggaagt acgagcagta catcaagtgg cctggcggaa gcggcagcag cctggatatc 3660
tcttctgaga tcggctccat caacaacacc gtgaacaagg tggaagaact gattgccgag 3720
agcaacgcct ggctgcaggc cgtgaatcct cacctggtca acaataccag catcatcgtg 3780
ctgtgcgtgc tggccgctat cttcgttgtg tggctggtgg ctctgacagg ctgtctggcc 3840
tactacatca agaagtccag cgccaccaga atggtcggaa tcggcagttc tcctgccggc 3900
aatccttacg tggcccagag cgccacaaaa atgtga 3936
<210> 16
<211> 3945
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 16
atgttcgtgt ttctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgcggacc 60
agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120
aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180
aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240
aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300
atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360
aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420
ctggacgtgt actatcacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480
gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540
cagggcaact tcaagaacct gcgcgagttc gtgttcaaga acatcgacgg ctacttcaag 600
atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660
ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720
gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780
gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840
ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900
ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960
accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020
aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080
gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140
tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200
cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260
tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320
tccaaagtcg gcggcaacta caattaccgg tacaggctgt tccggaagtc caatctgaag 1380
cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgcaacggc 1440
gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500
gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560
acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620
ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680
cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740
gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800
aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtacaga ggtgccagtg 1860
gccattcacg ccgatcagct gacccctact tggcgggtgt actccacagg cagcaatgtg 1920
tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980
gacatcccca tcggcgctgg catctgtgcc agctaccaga cacagaccaa cagcaggcgg 2040
agagccagat ctgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100
aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160
accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220
tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280
ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340
gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400
agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460
ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520
gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580
cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640
acaagcggct ggacatttgg agctggcgcc gctctgcaga tcccctttgc tatgcagatg 2700
gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760
atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820
agcgccctgg gaaagctgca gaacgtcgtg aaccagaacg cccaggcact gaacaccctg 2880
gtcaagcagc tgtcctccaa cttcggcgcc atctctagcg tgctgaacga tatcctgagc 2940
agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactccag 3000
tctctgcaga cctacgtgac ccagcagctg atcagagccg ccgagattag agccagcgct 3060
aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120
tgcggcaagg gctaccacct gatgagcttc cctcagtctg caccacacgg cgtggtgttt 3180
ctgcacgtga catacgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240
cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300
ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360
tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420
cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480
gacgtggacc tgggcgatat cagcggaatc aatgccagcg tggtcaacat ccagaaagag 3540
atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600
ctggggaagt acgagcagta catcaagtgg cctggcggct ccggcagcat cgacatctct 3660
aatgagctgg aaaacgtgaa cagctctctg agcagcgccc tcgagaagct ggatgagtct 3720
gatgccgctc tgagcaaagt gaacgtgcac ctgacaagca ccagcgccat ggccacctat 3780
atcgtgctga ccgtgatcgc cctgatcctg ggctttgttg gactcggcct gggctgcttc 3840
gccatgatca aagtgaagtc ccaggccaag actctgctgt ggctgggagc ccatgccgac 3900
agatcttaca tcctgcagag caagcccgct cagagcagca cttaa 3945
<210> 17
<211> 3825
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 17
atgttcgtgt ttctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgcggacc 60
agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120
aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180
aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240
aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300
atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360
aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420
ctggacgtgt actatcacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480
gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540
cagggcaact tcaagaacct gcgcgagttc gtgttcaaga acatcgacgg ctacttcaag 600
atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660
ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720
gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780
gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840
ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900
ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960
accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020
aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080
gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140
tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200
cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260
tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320
tccaaagtcg gcggcaacta caattaccgg tacaggctgt tccggaagtc caatctgaag 1380
cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgcaacggc 1440
gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500
gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560
acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620
ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680
cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740
gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800
aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtacaga ggtgccagtg 1860
gccattcacg ccgatcagct gacccctact tggcgggtgt actccacagg cagcaatgtg 1920
tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980
gacatcccca tcggcgctgg catctgtgcc agctaccaga cacagaccaa cagcaggcgg 2040
agagccagat ctgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100
aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160
accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220
tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280
ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340
gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400
agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460
ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520
gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580
cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640
acaagcggct ggacatttgg agctggcgcc gctctgcaga tcccctttgc tatgcagatg 2700
gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760
atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820
agcgccctgg gaaagctgca gaacgtcgtg aaccagaacg cccaggcact gaacaccctg 2880
gtcaagcagc tgtcctccaa cttcggcgcc atctctagcg tgctgaacga tatcctgagc 2940
agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactccag 3000
tctctgcaga cctacgtgac ccagcagctg atcagagccg ccgagattag agccagcgct 3060
aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120
tgcggcaagg gctaccacct gatgagcttc cctcagtctg caccacacgg cgtggtgttt 3180
ctgcacgtga catacgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240
cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300
ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360
tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420
cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480
gacgtggacc tgggcgatat cagcggaatc aatgccagcg tggtcaacat ccagaaagag 3540
atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600
ctggggaagt acgagcagta catcaagtgg cctggcggct ccggcagcta cagcaattgg 3660
tatatcgtgc tggtcatcgt gctgctgttc ggcaatctcg gatggtcact gctgctgact 3720
gtcctgctgt gccggtccag aaagcagcag aggcggtatc agcaggacga tagcgtggga 3780
agcgagcgcg gagttggagt gggaaccatc cagtacatga gctga 3825
<210> 18
<211> 3915
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 18
atgttcgtgt ttctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgcggacc 60
agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120
aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180
aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240
aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300
atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360
aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420
ctggacgtgt actatcacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480
gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540
cagggcaact tcaagaacct gcgcgagttc gtgttcaaga acatcgacgg ctacttcaag 600
atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660
ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720
gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780
gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840
ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900
ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960
accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020
aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080
gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140
tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200
cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260
tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320
tccaaagtcg gcggcaacta caattaccgg tacaggctgt tccggaagtc caatctgaag 1380
cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgcaacggc 1440
gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500
gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560
acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620
ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680
cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740
gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800
aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtacaga ggtgccagtg 1860
gccattcacg ccgatcagct gacccctact tggcgggtgt actccacagg cagcaatgtg 1920
tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980
gacatcccca tcggcgctgg catctgtgcc agctaccaga cacagaccaa cagcaggcgg 2040
agagccagat ctgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100
aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160
accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220
tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280
ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340
gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400
agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460
ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520
gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580
cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640
acaagcggct ggacatttgg agctggcgcc gctctgcaga tcccctttgc tatgcagatg 2700
gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760
atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820
agcgccctgg gaaagctgca gaacgtcgtg aaccagaacg cccaggcact gaacaccctg 2880
gtcaagcagc tgtcctccaa cttcggcgcc atctctagcg tgctgaacga tatcctgagc 2940
agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactccag 3000
tctctgcaga cctacgtgac ccagcagctg atcagagccg ccgagattag agccagcgct 3060
aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120
tgcggcaagg gctaccacct gatgagcttc cctcagtctg caccacacgg cgtggtgttt 3180
ctgcacgtga catacgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240
cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300
ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360
tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420
cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480
gacgtggacc tgggcgatat cagcggaatc aatgccagcg tggtcaacat ccagaaagag 3540
atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600
ctggggaagt acgagcagta catcaagtgg cctggcggct ccggcagcct gattcaagag 3660
gcccaggatc atgccaatgc cgctctggcc aaggtggaag agagcgacaa gtacctgaga 3720
gccgtgaccg gcggcaatta ctccaactgg tacatcgtgc tcgtgatcgt gctgctgttc 3780
ggcaatctcg gatggtcact gctgctgact gtcctgctgt gccggtccag aaagcagcag 3840
aggcggtatc agcaggacga tagcgtggga agcgagcgcg gagttggagt gggaaccatc 3900
cagtacatga gctga 3915
<210> 19
<211> 3966
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 19
atgttcgtgt ttctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgcggacc 60
agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120
aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180
aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240
aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300
atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360
aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420
ctggacgtgt actatcacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480
gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540
cagggcaact tcaagaacct gcgcgagttc gtgttcaaga acatcgacgg ctacttcaag 600
atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660
ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720
gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780
gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840
ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900
ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960
accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020
aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080
gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140
tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200
cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260
tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320
tccaaagtcg gcggcaacta caattaccgg tacaggctgt tccggaagtc caatctgaag 1380
cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgcaacggc 1440
gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500
gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560
acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620
ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680
cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740
gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800
aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtacaga ggtgccagtg 1860
gccattcacg ccgatcagct gacccctact tggcgggtgt actccacagg cagcaatgtg 1920
tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980
gacatcccca tcggcgctgg catctgtgcc agctaccaga cacagaccaa cagcaggcgg 2040
agagccagat ctgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100
aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160
accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220
tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280
ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340
gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400
agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460
ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520
gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580
cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640
acaagcggct ggacatttgg agctggcgcc gctctgcaga tcccctttgc tatgcagatg 2700
gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760
atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820
agcgccctgg gaaagctgca gaacgtcgtg aaccagaacg cccaggcact gaacaccctg 2880
gtcaagcagc tgtcctccaa cttcggcgcc atctctagcg tgctgaacga tatcctgagc 2940
agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactccag 3000
tctctgcaga cctacgtgac ccagcagctg atcagagccg ccgagattag agccagcgct 3060
aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120
tgcggcaagg gctaccacct gatgagcttc cctcagtctg caccacacgg cgtggtgttt 3180
ctgcacgtga catacgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240
cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300
ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360
tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420
cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480
gacgtggacc tgggcgatat cagcggaatc aatgccagcg tggtcaacat ccagaaagag 3540
atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600
ctggggaagt acgagcagta catcaagtgg cctggcggaa gcggcagcca gatcgtgtct 3660
gtggacccta tcgacatcag ctccgatatc gccaagatca actccagcat cgaggccgcc 3720
agagagcagc tggaactgag caaccagatc ctgagccgga tcaaccccag aatcgtgaat 3780
gacgagtccc tgattgccat catcgtgaca atcgtggtgc tgtccctgct ggtcatcggc 3840
ctgattgtgg tcctgagcgt gatgtataag aacctgaaga aggtccagcg cgcccaggcc 3900
gctatgatga tgcagcagat gagcagcagc cagcctgtga ccaccaagct gggcacccct 3960
ttttga 3966
<210> 20
<211> 3921
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 20
atgttcgtgt ttctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgcggacc 60
agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120
aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180
aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240
aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300
atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360
aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420
ctggacgtgt actatcacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480
gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540
cagggcaact tcaagaacct gcgcgagttc gtgttcaaga acatcgacgg ctacttcaag 600
atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660
ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720
gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780
gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840
ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900
ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960
accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020
aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080
gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140
tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200
cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260
tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320
tccaaagtcg gcggcaacta caattaccgg tacaggctgt tccggaagtc caatctgaag 1380
cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgcaacggc 1440
gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500
gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560
acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620
ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680
cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740
gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800
aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtacaga ggtgccagtg 1860
gccattcacg ccgatcagct gacccctact tggcgggtgt actccacagg cagcaatgtg 1920
tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980
gacatcccca tcggcgctgg catctgtgcc agctaccaga cacagaccaa cagcaggcgg 2040
agagccagat ctgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100
aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160
accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220
tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280
ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340
gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400
agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460
ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520
gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580
cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640
acaagcggct ggacatttgg agctggcgcc gctctgcaga tcccctttgc tatgcagatg 2700
gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760
atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820
agcgccctgg gaaagctgca gaacgtcgtg aaccagaacg cccaggcact gaacaccctg 2880
gtcaagcagc tgtcctccaa cttcggcgcc atctctagcg tgctgaacga tatcctgagc 2940
agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactccag 3000
tctctgcaga cctacgtgac ccagcagctg atcagagccg ccgagattag agccagcgct 3060
aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120
tgcggcaagg gctaccacct gatgagcttc cctcagtctg caccacacgg cgtggtgttt 3180
ctgcacgtga catacgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240
cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300
ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360
tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420
cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480
gacgtggacc tgggcgatat cagcggaatc aatgccagcg tggtcaacat ccagaaagag 3540
atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600
ctggggaagt acgagcagta catcaagtgg cctggcggct ccggcagcga tattagcgtg 3660
gaactgaacc gcgtgaacac cagcctgtct aaggtggaaa gcctgatcaa agagtccaac 3720
tccatcctcg acagcgtgaa ccctcagatc ctgaacgtga aaaccgtgat catcctggcc 3780
gtgattatcg gcctgatcgt tgtgtggtgc ttcatcctga cctgcctgat tgtgcggggc 3840
ttcatgctgc tcgtgaagca gcagaagttc aagggcctga gcgtgcagaa caacccctat 3900
gtgtccaaca acagccactg a 3921
<210> 21
<211> 3933
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 21
atgttcgtgt ttctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgcggacc 60
agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120
aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180
aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240
aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300
atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360
aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420
ctggacgtgt actatcacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480
gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540
cagggcaact tcaagaacct gcgcgagttc gtgttcaaga acatcgacgg ctacttcaag 600
atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660
ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720
gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780
gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840
ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900
ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960
accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020
aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080
gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140
tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200
cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260
tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320
tccaaagtcg gcggcaacta caattaccgg tacaggctgt tccggaagtc caatctgaag 1380
cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgcaacggc 1440
gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500
gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560
acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620
ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680
cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740
gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800
aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtacaga ggtgccagtg 1860
gccattcacg ccgatcagct gacccctact tggcgggtgt actccacagg cagcaatgtg 1920
tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980
gacatcccca tcggcgctgg catctgtgcc agctaccaga cacagaccaa cagcaggcgg 2040
agagccagat ctgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100
aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160
accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220
tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280
ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340
gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400
agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460
ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520
gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580
cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640
acaagcggct ggacatttgg agctggcgcc gctctgcaga tcccctttgc tatgcagatg 2700
gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760
atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820
agcgccctgg gaaagctgca gaacgtcgtg aaccagaacg cccaggcact gaacaccctg 2880
gtcaagcagc tgtcctccaa cttcggcgcc atctctagcg tgctgaacga tatcctgagc 2940
agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactccag 3000
tctctgcaga cctacgtgac ccagcagctg atcagagccg ccgagattag agccagcgct 3060
aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120
tgcggcaagg gctaccacct gatgagcttc cctcagtctg caccacacgg cgtggtgttt 3180
ctgcacgtga catacgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240
cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300
ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360
tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420
cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480
gacgtggacc tgggcgatat cagcggaatc aatgccagcg tggtcaacat ccagaaagag 3540
atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600
ctggggaagt acgagcagta catcaagtgg cctggcggat ctggcagccc tctggatatc 3660
tctagcgagc tgggcaaagt gaatcagagc ctgtccaacg tggaagatct gattgaccag 3720
agcaaccagc tgctgaacag agtgaacccc aacatcgtca acaacaccgc catcatcgtg 3780
acaatcgtgc tgctggtcct gctcgtgctg tggtgtctgg ccctgacaat cagcatcctg 3840
tatgtgtcca agcacgccgt gcggatgatc aagaccgtgc ctaatcctta cgtgatgcag 3900
gccaagtctc ccggcagcgc cacacagttt taa 3933
<210> 22
<211> 3903
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 22
atgttcgtgt ttctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgcggacc 60
agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120
aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180
aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240
aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300
atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360
aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420
ctggacgtgt actatcacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480
gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540
cagggcaact tcaagaacct gcgcgagttc gtgttcaaga acatcgacgg ctacttcaag 600
atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660
ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720
gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780
gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840
ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900
ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960
accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020
aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080
gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140
tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200
cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260
tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320
tccaaagtcg gcggcaacta caattaccgg tacaggctgt tccggaagtc caatctgaag 1380
cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgcaacggc 1440
gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500
gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560
acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620
ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680
cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740
gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800
aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtacaga ggtgccagtg 1860
gccattcacg ccgatcagct gacccctact tggcgggtgt actccacagg cagcaatgtg 1920
tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980
gacatcccca tcggcgctgg catctgtgcc agctaccaga cacagaccaa cagcaggcgg 2040
agagccagat ctgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100
aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160
accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220
tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280
ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340
gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400
agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460
ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520
gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580
cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640
acaagcggct ggacatttgg agctggcgcc gctctgcaga tcccctttgc tatgcagatg 2700
gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760
atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820
agcgccctgg gaaagctgca gaacgtcgtg aaccagaacg cccaggcact gaacaccctg 2880
gtcaagcagc tgtcctccaa cttcggcgcc atctctagcg tgctgaacga tatcctgagc 2940
agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactccag 3000
tctctgcaga cctacgtgac ccagcagctg atcagagccg ccgagattag agccagcgct 3060
aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120
tgcggcaagg gctaccacct gatgagcttc cctcagtctg caccacacgg cgtggtgttt 3180
ctgcacgtga catacgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240
cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300
ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360
tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420
cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480
gacgtggacc tgggcgatat cagcggaatc aatgccagcg tggtcaacat ccagaaagag 3540
atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600
ctggggaagt acgagcagta catcaagtgg cctggcggat ctggaagcga actgggccag 3660
ctgaacaaca gcatcagctc cgccaccgat aacctgcaga aggcccaaga gtccctgaac 3720
aagtctatca tccctgccgc cacctccagc tggctgatca tcctgctgtt tgtgctcgtg 3780
tccatcagcc tggtcatcgg ctgcatcagc atctacttca tctacaagca ctccaccacc 3840
aacagaagcc ggaacctgtc cagcgatatc atcagcaacc cctatatcca gaaggccaac 3900
tga 3903
<210> 23
<211> 3939
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 23
atgttcgtgt ttctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgcggacc 60
agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120
aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180
aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240
aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300
atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360
aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420
ctggacgtgt actatcacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480
gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540
cagggcaact tcaagaacct gcgcgagttc gtgttcaaga acatcgacgg ctacttcaag 600
atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660
ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720
gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780
gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840
ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900
ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960
accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020
aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080
gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140
tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200
cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260
tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320
tccaaagtcg gcggcaacta caattaccgg tacaggctgt tccggaagtc caatctgaag 1380
cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgcaacggc 1440
gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500
gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560
acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620
ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680
cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740
gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800
aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtacaga ggtgccagtg 1860
gccattcacg ccgatcagct gacccctact tggcgggtgt actccacagg cagcaatgtg 1920
tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980
gacatcccca tcggcgctgg catctgtgcc agctaccaga cacagaccaa cagcaggcgg 2040
agagccagat ctgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100
aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160
accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220
tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280
ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340
gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400
agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460
ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520
gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580
cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640
acaagcggct ggacatttgg agctggcgcc gctctgcaga tcccctttgc tatgcagatg 2700
gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760
atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820
agcgccctgg gaaagctgca gaacgtcgtg aaccagaacg cccaggcact gaacaccctg 2880
gtcaagcagc tgtcctccaa cttcggcgcc atctctagcg tgctgaacga tatcctgagc 2940
agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactccag 3000
tctctgcaga cctacgtgac ccagcagctg atcagagccg ccgagattag agccagcgct 3060
aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120
tgcggcaagg gctaccacct gatgagcttc cctcagtctg caccacacgg cgtggtgttt 3180
ctgcacgtga catacgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240
cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300
ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360
tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420
cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480
gacgtggacc tgggcgatat cagcggaatc aatgccagcg tggtcaacat ccagaaagag 3540
atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600
ctggggaagt acgagcagta catcaagtgg cctggcggaa gcggcagcct ggatatctct 3660
agcgagatcg gcaacatcaa caacaccgtg aaccgcgtgg aagatctgat tcaccagagc 3720
gaggaatggc tcgccaaagt gaaccctcac atcgtcaaca ataccacact gatcgtgctg 3780
tgcgtgctgt ctgccctggc tgtgatttgg ctggctgtgc tgaccgccat catcatctac 3840
ctgaggacaa agctgaaaac gatctcagcc ctggccgtga ccaataccat ccagtctaac 3900
ccctacgtca accagacaaa gcgcgagagc aagttctga 3939
<210> 24
<211> 10
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 24
ttagaaaaaa 10
<210> 25
<211> 10
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 25
acgggtagaa 10
<210> 26
<211> 21
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 26
aaggtccaac tctccaagcg g 21
<210> 27
<211> 23
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 27
gtcctcctta ctatcagtcc aca 23
<210> 28
<211> 1327
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 28
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser
145 150 155 160
Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp
165 170 175
Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe
180 185 190
Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile
195 200 205
Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu
210 215 220
Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu
225 230 235 240
Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp
245 250 255
Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr
260 265 270
Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp
275 280 285
Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe
290 295 300
Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro
305 310 315 320
Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe
325 330 335
Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn
340 345 350
Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn
355 360 365
Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys
370 375 380
Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile
385 390 395 400
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
405 410 415
Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile
420 425 430
Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn
435 440 445
Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg
450 455 460
Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly
465 470 475 480
Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln
485 490 495
Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser
500 505 510
Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser
515 520 525
Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu
530 535 540
Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe
545 550 555 560
Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp
565 570 575
Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly
580 585 590
Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val
595 600 605
Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala
610 615 620
Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val
625 630 635 640
Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn
645 650 655
Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr
660 665 670
Gln Thr Gln Thr Asn Ser Arg Gly Ser Ala Ser Ser Val Ala Ser Gln
675 680 685
Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala
690 695 700
Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val
705 710 715 720
Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys
725 730 735
Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu
740 745 750
Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile
755 760 765
Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys
770 775 780
Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe
785 790 795 800
Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile
805 810 815
Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile
820 825 830
Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile
835 840 845
Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr
850 855 860
Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile
865 870 875 880
Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe
885 890 895
Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn
900 905 910
Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala
915 920 925
Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly
930 935 940
Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu
945 950 955 960
Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn
965 970 975
Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp
980 985 990
Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln
995 1000 1005
Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala
1010 1015 1020
Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe
1025 1030 1035 1040
Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1045 1050 1055
Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn
1060 1065 1070
Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro
1075 1080 1085
Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln
1090 1095 1100
Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val
1105 1110 1115 1120
Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr
1125 1130 1135
Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys
1140 1145 1150
Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser
1155 1160 1165
Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu
1170 1175 1180
Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu
1185 1190 1195 1200
Leu Gly Lys Tyr Glu Gln Gly Ser Gly Ser Gly Tyr Ile Pro Glu Ala
1205 1210 1215
Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Phe
1220 1225 1230
Leu Ser Thr Phe Leu Gly Gly Ser Leu Gly Asn Val Asn Asn Ser Ile
1235 1240 1245
Ser Asn Ala Leu Asn Lys Leu Glu Glu Ser Asn Arg Lys Leu Asp Lys
1250 1255 1260
Val Asn Val Lys Leu Thr Ser Thr Ser Ala Leu Ile Thr Tyr Ile Val
1265 1270 1275 1280
Leu Thr Ile Ile Ser Leu Val Phe Gly Ile Leu Ser Leu Ile Leu Ala
1285 1290 1295
Cys Tyr Leu Met Tyr Lys Gln Lys Ala Gln Gln Lys Thr Leu Leu Trp
1300 1305 1310
Leu Gly Asn Asn Thr Leu Asp Gln Met Arg Ala Thr Thr Lys Met
1315 1320 1325
<210> 29
<211> 3984
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 29
atgtttgttt ttcttgtttt attgccacta gtctctagtc agtgtgttaa tcttagaacc 60
agaactcaat taccccctgc atacactaat tctttcacac gtggtgttta ttaccctgac 120
aaagttttca gatcctcagt tttacattca actcaggact tgttcttacc tttcttttcc 180
aatgttactt ggttccatgc tatacatgtc tctgggacca atggtactaa gaggtttgat 240
aaccctgtcc taccatttaa tgatggtgtt tattttgctt ccactgagaa gtctaacata 300
ataagaggct ggatttttgg tactacttta gattcgaaga cccagtccct acttattgtt 360
aataacgcta ctaatgttgt tattaaagtc tgtgaatttc aattttgtaa tgatccattt 420
ttggatgttt attaccacaa aaacaacaaa agttggatgg aaagtggagt ttattctagt 480
gcgaataatt gcacttttga atatgtctct cagccttttc ttatggacct tgaaggaaaa 540
cagggtaatt tcaaaaatct tagggaattt gtgtttaaga atattgatgg ttattttaaa 600
atatattcta agcacacgcc tattaattta gtgcgtgatc tccctcaggg tttttcggct 660
ttagaaccat tggtagattt gccaataggt attaacatca ctaggtttca aactttactt 720
gctttacata gaagttattt gactcctggt gattcttctt caggttggac agctggtgct 780
gcagcttatt atgtgggtta tcttcaacct aggacttttc tattaaaata taatgaaaat 840
ggaaccatta cagatgctgt agactgtgca cttgaccctc tctcagaaac aaagtgtacg 900
ttgaaatcct tcactgtaga aaaaggaatc tatcaaactt ctaactttag agtccaacca 960
acagaatcta ttgttagatt tcctaatatt acaaacttgt gcccttttgg tgaagttttt 1020
aacgccacca gatttgcatc tgtttatgct tggaacagga agagaatcag caactgtgtt 1080
gctgattatt ctgtcctata taattccgca tcattttcca cttttaagtg ttatggagtg 1140
tctcctacta aattaaatga tctctgcttt actaatgtct atgcagattc atttgtaatt 1200
agaggtgatg aagtcagaca aatcgctcca gggcaaactg gaaagattgc tgattataat 1260
tataaattac cagatgattt tacaggctgc gttatagctt ggaattctaa caatcttgat 1320
tctaaggttg gtggtaatta taattaccgg tatagattgt ttaggaagtc taatctcaaa 1380
ccttttgaga gagatatttc aactgaaatc tatcaggccg gtagcaaacc ttgtaatggt 1440
gttgaaggtt ttaattgtta ctttccttta caatcatatg gtttccaacc cactaatggt 1500
gttggttacc aaccatacag agtagtagta ctttcttttg aacttctaca tgcaccagca 1560
actgtttgtg gacctaaaaa gtctactaat ttggttaaaa acaaatgtgt caatttcaac 1620
ttcaatggtt taacaggcac aggtgttctt actgagtcta acaaaaagtt tctgcctttc 1680
caacaatttg gcagagacat tgctgacact actgatgctg tccgtgatcc acagacactt 1740
gagattcttg acattacacc atgttctttt ggtggtgtca gtgttataac accaggaaca 1800
aatacttcta accaggttgc tgttctttat cagggtgtta actgcacaga agtccctgtt 1860
gctattcatg cagatcaact tactcctact tggcgtgttt attctacagg ttctaatgtt 1920
tttcaaacac gtgcaggctg tttaataggg gctgaacatg tcaacaactc atatgagtgt 1980
gacataccca ttggtgcagg tatatgcgct agttatcaga ctcagactaa ttctcgtggc 2040
tccgcatcca gtgtagctag tcaatccatc attgcctaca ctatgtcact tggtgcagaa 2100
aattcagttg cttactctaa taactctatt gccataccca caaattttac tattagtgtt 2160
accacagaaa ttctaccagt gtctatgacc aagacatcag tagattgtac aatgtacatt 2220
tgtggtgatt caactgaatg cagcaatctt ttgttgcaat atggcagttt ttgtacacaa 2280
ttaaaccgtg ctttaactgg aatagctgtt gaacaagaca aaaacaccca agaagttttt 2340
gcacaagtca aacaaattta caaaacacca ccaattaaag attttggtgg ttttaatttt 2400
tcacaaatat taccagatcc atcaaaacca agcaagaggt catttattga agatctactt 2460
ttcaacaaag tgacacttgc agatgctggc ttcatcaaac aatatggtga ttgccttggt 2520
gatattgctg ctagagacct catttgtgca caaaagttta acggccttac tgttttgcca 2580
cctttgctca cagatgaaat gattgctcaa tacacttctg cactgttagc gggtacaatc 2640
acttctggtt ggacctttgg tgcaggtgct gcattacaaa taccatttgc tatgcaaatg 2700
gcttataggt ttaatggtat tggagttaca cagaatgttc tctatgagaa ccaaaaattg 2760
attgccaacc aatttaatag tgctattggc aaaattcaag actcactttc ttccacagca 2820
agtgcacttg gaaaacttca aaatgtggtc aaccaaaatg cacaagcttt aaacacgctt 2880
gttaaacaac ttagctccaa ttttggtgca atttcaagtg ttttaaatga tatcctttca 2940
cgtcttgacc ctcccgaggc tgaagtgcaa attgataggt tgatcacagg cagacttcaa 3000
agtttgcaga catatgtgac tcaacaatta attagagctg cagaaatcag agcttctgct 3060
aatcttgctg ctactaaaat gtcagagtgt gtacttggac aatcaaaaag agttgatttt 3120
tgtggaaagg gctatcatct tatgtccttc cctcagtcag cacctcatgg tgtagtcttc 3180
ttgcatgtga cttatgtccc tgcacaagaa aagaacttca caactgctcc tgccatttgt 3240
catgatggaa aagcacactt tcctcgtgaa ggtgtctttg tttcaaatgg cacacactgg 3300
tttgtaacac aaaggaattt ttatgaacca caaatcatta ctacagacaa cacatttgtg 3360
tctggtaact gtgatgttgt aataggaatt gtcaacaaca cagtttatga tcctttgcaa 3420
cctgaattag actcattcaa ggaggagtta gataaatatt ttaagaatca tacatcacca 3480
gatgttgatt taggtgacat ctctggcatt aatgcttcag ttgtaaacat tcaaaaagaa 3540
attgaccgcc tcaatgaggt tgccaagaat ttaaatgaat ctctcatcga tctccaagaa 3600
cttggaaagt atgagcaggg atccggaagc ggttatattc ctgaagctcc aagagatggg 3660
caagcttacg ttcgtaaaga tggcgaatgg gtattccttt ctaccttttt aggaggatcc 3720
cttgggaatg tcaacaactc gatcagtaat gctttgaata agttagagga aagcaacaga 3780
aaactagaca aagtcaatgt caaactgact agcacatctg ctctcattac ctatatcgtt 3840
ttgactatca tatctcttgt ttttggtata cttagcctga ttctagcatg ctacctaatg 3900
tacaagcaaa aggcgcaaca aaagacctta ttatggcttg ggaataatac tctagatcag 3960
atgagagcca ctacaaaaat gtga 3984

Claims (10)

1.一种展示新冠病毒S蛋白的融合蛋白，其特征在于，包含新冠病毒S蛋白的胞外域序列和含禽副黏病毒科病毒F蛋白的跨膜结构域和胞内结构域的序列。
2.根据权利要求1所述融合蛋白，其特征在于，所述禽副黏病毒科病毒包括以下一种或几种血清型：APMV-2、APMV-3、APMV-4、APMV-5、APMV-6、APMV-7、APMV-8、APMV-9、APMV-10、APMV-11或APMV-12；
优选的，所述禽副黏病毒科病毒包括以下一种或几种血清型：APMV-3、APMV-5、APMV-7和APMV-8血清型。
3.根据权利要求1所述的融合蛋白，其特征在于，所述新冠S蛋白的胞外结构域来源于新冠原始毒株或变异株。
4.根据权利要求3所述的融合蛋白，其特征在于，所述新冠S蛋白的胞外结构域序列还包括以下一种或几种蛋白编码序列：S2P，S6P，S2P/GSAS；
所述S2P是将所述新冠S蛋白胞外域进行K986P和V987P突变所形成的蛋白编码序列；
所述S2P/GSAS蛋白编码序列是在S2P基础上将第682～685位氨基酸RRAR突变为GSAS所形成的蛋白编码序列；
所述S6P蛋白编码序列是在S2P基础上进行F817P、A892P、A899P和A942P突变所形成的蛋白编码序列。
5.一种编码权利要求1～4任意一项所述融合蛋白的融合基因。
6.一种包含权利要求5所述融合基因的重组病毒载体。
7.根据权利要求6所述重组病毒载体，其特征在于，所述重组病毒载体以新城疫病毒载体为骨架载体。
8.根据权利要求7所述重组病毒载体，其特征在于，所述融合基因以表达盒子形式插入所述新城疫病毒载体的P基因和M基因之间。
9.一种由权利要求7所述重组病毒载体制备得到的重组病毒粒子或疫苗株。
10.权利要求1～4任意一项所述融合蛋白、权利要求5所述融合基因、权利要求6～8任意一项所述重组病毒载体或权利要求8所述重组病毒粒子或疫苗株在制备防控新冠肺炎的疫苗中的应用。
CN202111541851.3A 2021-12-16 2021-12-16 一种展示新冠s蛋白的融合蛋白和重组病毒粒子及其应用 Pending CN114213547A (zh)

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