CN114369587A - 牛痘病毒加帽酶突变体、重组载体、重组工程菌及其应用 - Google Patents
牛痘病毒加帽酶突变体、重组载体、重组工程菌及其应用 Download PDFInfo
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Abstract
本发明涉及一种牛痘病毒加帽酶突变体、重组载体、重组工程菌及其应用。该牛痘病毒加帽酶突变体包括：(a)、由如SEQ ID No.2所示的氨基酸序列缺失、替代或增加一个或多个氨基酸组成的多肽；或，(b)、与如SEQ ID No.2所示的氨基酸序列组成的多肽具有至少90％同源性的多肽。上述牛痘病毒加帽酶突变体在45℃下的半衰期在35min以上，高于野生型牛痘病毒加帽酶突变体的半衰期，在较高的温度下对mRNA加帽时，仍然表现出优良的的催化活性，在临床医药、流感疫苗、肿瘤疫苗、生物制药等领域都能发挥重要作用。
Description
技术领域
本发明涉及生物技术领域，特别是涉及一种牛痘病毒加帽酶突变体、重组载体、重组工程菌及其应用。
背景技术
真核生物中mRNA经转录后修饰在5'端形成一个特殊结构，即帽子结构，该结构对mRNA的稳定、转运与翻译过程均有较重要作用。牛痘病毒加帽酶是催化形成帽子结构的有效酶，其由D1和D12两个亚基组成，兼具RNA三磷酸酯酶活性、鸟苷酰基转移酶活性和鸟嘌呤甲基转移酶活性，可将7-甲基鸟嘌呤帽结构(m7Gppp)连接到RNA的5'末端(m7Gppp5'N)。牛痘病毒加帽酶，在合适浓度的加帽缓冲液(Capping buffer)，鸟苷三磷酸(GTP)，S-腺苷甲硫氨酸(SAM)等存在条件下，能够在一个小时之内对RNA进行加帽，并且保证正确的方向，耐热的牛痘病毒加帽酶突变体，对mRNA在流行病疫苗以及肿瘤疫苗等多个领域，具有重要研究价值。然而，市场上大多数牛痘病毒加帽酶突变体的热稳定性较差，难以满足实际需求。
发明内容
基于此，有必提供一种热稳定性较好的牛痘病毒加帽酶突变体、重组载体、重组工程菌及其应用。
一种牛痘病毒加帽酶突变体，所述牛痘病毒加帽酶突变体包括：
(a)、由如SEQ ID No.2所示的氨基酸序列缺失、替代或增加一个或多个氨基酸组成的多肽；或，
(b)、与如SEQ ID No.2所示的氨基酸序列组成的多肽具有至少90％同源性的多肽。
研究发现，包括由如SEQ ID No.2所示的氨基酸序列缺失、替代或增加一个或多个氨基酸得到的多肽；或，与如SEQ ID No.2所示的氨基酸序列组成的多肽具有至少90％同源性的多肽的牛痘病毒加帽酶突变体具有较好的热稳定性。经试验验证，上述牛痘病毒加帽酶突变体在45℃下的半衰期在35min以上，高于野生型牛痘病毒加帽酶突变体的半衰期，尤其是含有如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变得到的多肽的牛痘病毒加帽酶突变体在45℃下半衰期大约是野生型牛痘病毒加帽酶的3倍，在较高的温度下对mRNA加帽时，仍然表现出优良的的催化活性，在临床医药、流感疫苗、肿瘤疫苗、生物制药等领域都能发挥重要作用。
其中一个实施例中，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列中第424位氨基酸、第461位氨基酸、第513位氨基酸及第750位氨基酸中的至少一个发生突变得到的多肽。
其中一个实施例中，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列发生V424I突变、Y461F突变、I513V突变及V750L突变中至少一种得到的多肽。
其中一个实施例中，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列发生V424I突变、Y461F突变、I513V突变、V750L突变中的任意一种得到的多肽。
其中一个实施例中，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变、V750L突变中的任意两种得到的多肽。
其中一个实施例中，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变、V750L突变中的任意三种得到的多肽。
其中一个实施例中，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变、V750L突变得到的多肽。
其中一个实施例中，所述牛痘病毒加帽酶突变体的氨基酸序列为如SEQ ID No.3～SEQ ID No.17所示的序列中的一种。
其中一个实施例中，所述牛痘病毒加帽酶突变体的编码序列包括：
(a)、与如SEQ ID No.1所示的核苷酸序列组成的多核苷酸具有至少90％同源性的多核苷酸；或，
(b)、由如SEQ ID No.1所示的核苷酸序列缺失、替代或增加一个或多个碱基得到的多核苷酸。
其中一个实施例中，所述牛痘病毒加帽酶突变体的核苷酸序列为如SEQ ID No.28～SEQ ID No.42所示的序列中的一种。
其中一个实施例中，所述牛痘病毒加帽酶突变体为可溶性酶、固定化酶或者基因工程酶。
一种重组载体，含有上述牛痘病毒加帽酶突变体的编码序列。
其中一个实施例中，包括如下步骤：采用第一扩增引物对对第一载体进行PCR扩增，得到重组载体，其中，所述第一载体含有如SEQ ID No.2所示的氨基酸序列对应的编码序列，所述第一扩增引物对含有所述牛痘病毒加帽酶突变体的突变位点对应的核苷酸序列。
其中一个实施例中，所述第一扩增引物对选自如下引物对中的至少一对：核苷酸序列如SEQ ID No.20和SEQ ID No.21所示的引物对、核苷酸序列如SEQ ID No.22和SEQ IDNo.23所示的引物对、核苷酸序列如SEQ ID No.24和SEQ ID No.25所示的引物对、核苷酸序列如SEQ ID No.26和SEQ ID No.27所示的引物对。
一种重组工程菌，含上述重组载体。
上述牛痘病毒加帽酶突变体、上述重组载体或者上述重组工程菌在催化mRNA加帽中的应用。
附图说明
图1为氨基酸序列如SEQ ID No.2所示的牛痘病毒加帽酶的蛋白模拟晶体结构示意图。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合具体实施例及附图对本发明的具体实施方式做详细的说明。在下面的描述中阐述了很多具体细节以便于充分理解本发明。但是本发明能够以很多不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似改进，因此本发明不受下面公开的具体实施的限制。
本发明一实施方式提供一种牛痘病毒加帽酶突变体包括：
(a)、由如SEQ ID No.2所示的氨基酸序列缺失、替代或增加一个或多个氨基酸组成的多肽；或，
(b)、与如SEQ ID No.2所示的氨基酸序列组成的多肽具有至少90％同源性的多肽。
研究发现，包括由如SEQ ID No.2所示的氨基酸序列缺失、替代或增加一个或多个氨基酸得到的多肽；或，与如SEQ ID No.2所示的氨基酸序列组成的多肽具有至少90％同源性的多肽的牛痘病毒加帽酶突变体具有较好的热稳定性。经试验验证，上述牛痘病毒加帽酶突变体在45℃下的半衰期在35min以上，高于野生型牛痘病毒加帽酶突变体的半衰期，尤其是含有如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变得到的多肽的牛痘病毒加帽酶突变体在45℃下半衰期大约是野生型牛痘病毒加帽酶的3倍，在较高的温度下对mRNA加帽时，仍然表现出优良的的催化活性，在临床医药、流感疫苗、肿瘤疫苗、生物制药等领域都能发挥重要作用。
如SEQ ID No.2所示的氨基酸序列为来源于Western Reserve的野生型牛痘病毒加帽酶，命名为VCE，包含D1R和D12L两个亚基。编码该蛋白的核苷酸序列为SEQ ID No.1。
在其中一个实施例中，牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列中第424位氨基酸、第461位氨基酸、第513位氨基酸及第750位氨基酸中的至少一个发生突变得到的多肽。
其中，牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列发生V424I突变、Y461F突变、I513V突变、V750L突变中的任意一种得到的多肽。
牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变、V750L突变中的任意两种得到的多肽。
牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变、V750L突变中的任意三种得到的多肽。
牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变、V750L突变得到的多肽。
在一个具体示例中，牛痘病毒加帽酶突变体的氨基酸序列为如SEQ ID No.3～SEQID No.17所示的序列中的一种。
其中一个实施例中，牛痘病毒加帽酶突变体的编码序列包括：
(a)、与如SEQ ID No.1所示的核苷酸序列组成的多核苷酸具有至少90％同源性的多核苷酸；或，
(b)、由如SEQ ID No.1所示的核苷酸序列缺失、替代或增加一个或多个碱基得到的多核苷酸。
在一个具体示例中，牛痘病毒加帽酶突变体的核苷酸序列为如SEQ ID No.28～SEQ ID No.42所示的序列中的一种。
由于同一氨基酸可由几种不同的密码子来决定，故同一氨基酸可对应不同的核苷酸序列。因此本申请中的牛痘病毒加帽酶突变体的氨基酸序列，包括由如SEQ ID No.1所示核苷酸序列进行1个或几个核苷酸取代而得到的密码子同义突变的核苷酸序列所编码得到。本领域技术人员可以根据本申请公开的牛痘病毒加帽酶突变体的氨基酸序列，根据现有分子生物学技术，采用cDNA克隆和定点突变的方法或其他适合的方法获得本申请的牛痘病毒加帽酶突变体，因此，编码上述牛痘病毒加帽酶突变体的核苷酸序列并不仅限于如SEQID No.1所示的核苷酸序列。如果编码得到的蛋白与牛痘病毒加帽酶突变体没有明显的功能差异，也包括在本发明的范围内。
此外，由于蛋白编码序列的多态性及变异，天然存在的蛋白质会出现基因突变，编码序列中碱基被缺失、替代或增加，或氨基酸的缺失、插入、取代或其它变异，从而导致蛋白质的氨基酸序列出现一个或多个氨基酸被缺失、替代或增加。因此，存在着一些生理和生物活性上基本等同于无变异蛋白质的蛋白。这些结构不同于相应的蛋白质，但与该蛋白质没有明显的功能差异的多肽或蛋白称为功能等同变异体。
功能等同的变异体同样适用于通过缺失、插入和突变等人工手段改变一个或多个密码子，从而向一种蛋白质的氨基酸序列中导入这类变异而制成的多肽。尽管这样能获得更多不同形式的变异体，但所得的变异体作为功能等同变异体的前提是其生理活性基本等同于原始无变异蛋白质的活性。
一般的，功能等同变异体的编码序列是同源的，因此，由至少一种改变(如蛋白质的编码序列中一个或多个碱基的缺失、插入或取代或者蛋白质的氨基酸序列中有一个或多个氨基酸缺失、插入或取代)所得的多肽或蛋白一般具有功能上等同于所述蛋白质的活性，因此，由上述核苷酸序列编码的到的多肽或上述氨基酸序列组成的多肽，如果编码得到的蛋白与牛痘病毒加帽酶突变体没有明显的功能差异，也包括在本发明的范围内。
其中一个实施例中，牛痘病毒加帽酶突变体为可溶性酶、固定化酶或者基因工程酶。
上述牛痘病毒加帽酶突变体具有较高的热稳定性，在较高的温度下对mRNA加帽时，仍然表现出优良的的催化活性，在临床医药、流感疫苗、肿瘤疫苗、生物制药等领域都能发挥重要作用。
本发明一实施方式提供一种重组载体，含有上述牛痘病毒加帽酶突变体的编码序列。
其中，重组载体为克隆载体或表达载体。
具体地，重组载体为含有上述牛痘病毒加帽酶突变体的编码序列的pQE80L载体。需要说明的是，重组载体不限于为含有上述牛痘病毒加帽酶突变体的编码序列的pQE80L载体，也可以将牛痘病毒加帽酶突变体基因整合到其他载体上，例如可以为pET21b、pET22b、pET32a、pQE30等载体。
本发明一实施方式提供上述重组载体的制备方法，包括如下步骤：采用第一扩增引物对对第一载体进行PCR扩增，得到重组载体，其中，第一载体含有如SEQ ID No.2所示的氨基酸序列对应的编码序列。第一扩增引物对含有所述牛痘病毒加帽酶突变体的突变位点对应的核苷酸序列。
其中，第一扩增引物对选自如下引物对中的至少一对：核苷酸序列如SEQ IDNo.20和SEQ ID No.21所示的引物对、核苷酸序列如SEQ ID No.22和SEQ ID No.23所示的引物对、核苷酸序列如SEQ ID No.24和SEQ ID No.25所示的引物对、核苷酸序列如SEQ IDNo.26和SEQ ID No.27所示的引物对。
需要说明的是，牛痘病毒加帽酶突变体的单点突变体的构建中，以上述第一扩增引物对中的一对进行PCR扩增。牛痘病毒加帽酶突变体的多点突变体的构建中，对一个突变位点进行单点突变后，再进行第二突变位点进行突变，依次叠加获得。具体地，按照以下方式进行：一个突变位点的扩增引物对扩增后，再用另一个突变位点的扩增引物对对含有在先突变的扩增产物进行扩增。
在其中一个实施例中，采用第一扩增引物对对第一载体进行PCR扩增的步骤之前，还包括构建第一载体的步骤。
其中，构建第一载体的步骤包括：采用序列如SEQ ID No.18～SEQ ID No.19所示的目的基因扩增引物对扩增目的基因，目的基因为如SEQ ID No.2所示的氨基酸序列对应的编码序列；将目的基因连接到空载体中，转化，提取阳性质粒，得到第一载体。具体地，如SEQ ID No.18所示的序列为：5’-CGCATATGATGGATGCCAACGTAGTATCATC-3’(即上游引物，带下划线碱基为限制性内切酶NdeI识别位点)，如SEQ ID No.19所示的序列为：5’-TCAGCTCT CGAGTTACCGCTTAGAAAAGACAT-3’(即下游引物，带下划线碱基为限制性内切酶XhoI识别位点)。
在其中一个实施例中，在采用第一扩增引物对对第一载体进行PCR扩增的步骤之前，还包括如下步骤：筛选牛痘病毒加帽酶突变体的突变位点。
其中，筛选牛痘病毒加帽酶突变体的突变位点的方法包括：通过在NCBI数据库(http://www.ncbi.nlm.nih.gov/)中搜索牛痘病毒加帽酶氨基酸序列(如SEQ ID No.2所示)，去除重复出现的相同序列后选取与目标蛋白序列一致性(identity)大于50％的蛋白质序列，然后进行序列比对及Consensus sequence分析，并对野生型牛痘病毒加帽酶的蛋白模拟晶体结构进行模拟，然后进行突变位点分析和设计，发现氨基酸序列如SEQ ID No.2所示的野生型牛痘病毒加帽酶在第424位、第461位、第513位、第812位、第750位的氨基酸对该酶的热稳定性影响较大，同时发现并验证如SEQ ID No.2所示的氨基酸序列发生V424I突变、Y461F突变、I513V突变、V750L突变中的至少一种得到的牛痘病毒加帽酶突变体的热稳定性较高。
蛋白质工程是以蛋白质分子的结构规律及其生物功能的关系作为基础，通过化学、物理和分子生物学的手段进行基因修饰或基因合成，对现有蛋白质进行改造或制造一种新的蛋白质以满足人类对生产和生活的需求。理性设计是蛋白质工程改造中最常用的方法，利用计算机辅助分子模型结合定点突变，以实现蛋白质功能优化。Consensus Concept理论是基于同源蛋白的氨基酸序列信息，从进化的角度分析能提高改善蛋白功能的信息。本发明以Consensus Concept理论为指导思想，对牛痘病毒加帽酶突变体家族序列进行整合分析，并结合生物信息学及晶体学方法辅助，进行突变位点分析和设计，获得具高稳定性的牛痘病毒加帽酶突变体。
上述重组载体的构建方法能够表达高稳定性的牛痘病毒加帽酶突变体的重组载体。上述重组载体能够用于生产牛痘病毒加帽酶突变体，以用于mRNA加帽，便于其在临床医药、流感疫苗、肿瘤疫苗、生物制药等领域发挥重要作用。
本发明一实施方式提供一种重组工程菌含有上述实施方式的重组载体。
上述重组工程菌用于生产牛痘病毒加帽酶突变体，以用于mRNA加帽，便于其在临床医药、流感疫苗、肿瘤疫苗、生物制药等领域发挥重要作用；并且构建的高效表达的重组工程菌，具有其培养周期短、培养条件简单、目的蛋白产量高、纯化简单的优点。
进一步地，重组工程菌为含有上述实施方式的重组载体的大肠杆菌。可选地，重组工程菌为含有上述实施方式的重组载体的大肠杆菌BL21(DE3)。需要说明的是，重组工程菌不限于为含有上述实施方式的重组载体的大肠杆菌，也可以使用革兰氏阳性菌、革兰氏阴性菌、酵母和真菌等微生物宿主进行目的蛋白的表达。
以下为具体实施例部分。
实施例中采用试剂和仪器如非特别说明，均为本领域常规选择。实施例中未注明具体条件的实验方法，通常按照常规条件，例如文献、书本中所述的条件或者试剂盒生产厂家推荐的方法实现。实施例中所使用的试剂均为市售。
以下实施例中，如特别说明，基因来源：牛痘病毒加帽酶来源于Western Reserve的野生型牛痘病毒加帽酶，命名为VCE，包含D1R和D12L两个亚基，编码该蛋白的核苷酸序列为SEQ ID No.1，氨基酸序列为SEQ ID No.2。VCE基因由苏州金唯智生物科技有限公司提供；PCR扩增酶为东洋纺提供的KOD高保真聚合酶。
实施例1
1、野生型牛痘病毒加帽酶基因的克隆
将野生型牛痘病毒加帽酶基因以大肠杆菌为宿主细胞进行密码子优化，得到优化的牛痘病毒加帽酶基因，命名为VCE，其核苷酸序列为SEQ ID No.1，表达的氨基酸序列为SEQ ID No.2。
以SEQ ID No.1作为目的基因，采用上游扩增引物SEQ ID No.18和下游扩增引物SEQ ID No.19扩增目的基因。扩增条件为：在95℃下扩增2min，然后在56℃下扩增20sec、在72℃下扩增90sec，共30个循环，最后在72℃下扩增10min。
待反应结束，采用1.5％琼脂糖凝胶电泳检测PCR扩增产物，得到1.0kb的条带，其长度符合预期结果。按照市售DNA胶回收试剂盒标准操作，回收、纯化该目的片段，使用限制性核酸内切酶XhoI和NdeI对该目的片段以及pET28a质粒进行双酶切，然后采用T4 DNA连接酶进行连接，将得到的连接产物转化至大肠杆菌BL21(DE3)感受态细胞中，将转化细胞涂布于含有100μg/mL卡那霉素的LB平板上，提取阳性克隆质粒，进行测序，结果显示克隆的牛痘病毒加帽酶基因序列正确，且已正确接入pET28a质粒，得到重组质粒pET28a-VCE。
2.VCE蛋白的表达和纯化
将甘油管中的工程菌按体积比1％接种到含100μg/mL Kan的4mL LB培养基试管中，在37℃、220rpm条件下培养12h；取菌液4mL转接至含100μg/mL Kan的1L LB培养基摇瓶中，在37℃、220rpm条件下培养2.5h，使OD600达到0.6-0.8，加入1mM IPTG诱导剂，在25℃、200rpm条件下诱导培养14h。将发酵后收获的大肠杆菌菌体悬液超声破碎，再经过一步Ni-NTA亲和层析处理，得到纯度＞95％的VCE蛋白，氨基酸序列为SEQ ID No.2。
实施例2
牛痘病毒加帽酶突变体的构建、表达及纯化
本申请对野生型牛痘病毒加帽酶的蛋白模拟晶体结构进行模拟、根据蛋白模拟晶体结构进行突变位点分析和设计，发现氨基酸序列如SEQ ID No.2所示的野生型牛痘病毒加帽酶在第424位、第461位、第513位、第812位、第750位的氨基酸对该酶的热稳定性影响较大，同时发现并验证如SEQ ID No.2所示的氨基酸序列发生V424I突变、Y461F突变、I513V突变、V750L突变中的至少一种得到的牛痘病毒加帽酶突变体的热稳定性较高。该野生型牛痘病毒加帽酶的蛋白模拟晶体结构示意图如图1所示。
1、VCE蛋白单点突变体的构建
以实施例1得到的重组质粒pET28a-VCE为模板，以带有突变位点的一对互补的寡核苷酸为扩增引物，用KOD高保真酶(由TakaRa公司提供)进行全质粒PCR扩增，获得具有特定突变位点的重组质粒；
其中，所采用的扩增引物对为：
(1)突变位点V424I：上游扩增引物的序列如SEQ ID No.20所示，下游扩增引物的序列如SEQ ID No.21所示。
(2)突变位点Y461F：上游扩增引物的序列如SEQ ID No.22所示，下游扩增引物的序列如SEQ ID No.23所示。
(3)突变位点I513V：上游扩增引物的序列如SEQ ID No.24所示，下游扩增引物的序列如SEQ ID No.25所示。
(4)突变位点V750L：上游扩增引物的序列如SEQ ID No.26所示，下游扩增引物的序列如SEQ ID No.27所示。
扩增条件为：在95℃下扩增2min，然后在56℃下扩增20sec、在72℃下扩增90sec，共30个循环，最后在72℃下扩增10min；胶回收PCR扩增产物，采用DpnI酶(由Fermentas公司提供)在37℃条件下消化胶回收产物2h，降解初始模板；将消化产物转化至大肠杆菌BL21(DE3)感受态细胞中，涂布到含有100μg/mL卡那霉素LB琼脂平板上，37℃过夜培养，筛选阳性克隆，测序验证，得到含牛痘病毒加帽酶单点突变体的重组菌。
2、VCE蛋白组合突变体的构建
使用与单点突变体相似的构建方法，将稳定性提高的单点突变体累加组合，在SEQID No.2所示的氨基酸序列选择多个突变位点进行组合，如从上述4个突变位点中选择2～4个突变位点进行组合，分别得到不同的牛痘病毒加帽酶组合突变体：
(1)选择2个突变位点进行组合，可构建6种热稳定性提高的牛痘病毒加帽酶突变体及牛痘病毒加帽酶组合突变体，其组合突变位点分别为：V424I/Y461F、V424I/I513V、V424I/V750L、Y461F/I513V、Y461F/V750L、I513V/V750L；该6种热稳定性提高的牛痘病毒加帽酶组合突变体的氨基酸序列分别如SEQ ID No.7、SEQ ID No.8、SEQ ID No.9、SEQ IDNo.10、SEQ ID No.11、SEQ ID No.12所示。
(2)选择3个突变位点进行组合，可构建4种热稳定性提高的牛痘病毒加帽酶组合突变体，其组合突变位点分别为：V424I/Y461F/I513V、V424I/Y461F/V750L、V424I/I513V/V750L、Y461F/I513V/V750L，该4种热稳定性提高的牛痘病毒加帽酶组合突变体的氨基酸序列分别如SEQ ID No.13、SEQ ID No.14、SEQ ID No.15、SEQ ID No.16所示。
(3)选择4个突变位点进行组合，可构建1种热稳定性提高的牛痘病毒加帽酶组合突变体，其组合突变位点分别为：V424I/Y461F/I513V/V750L，该种热稳定性提高的牛痘病毒加帽酶组合突变体的氨基酸序列如SEQ ID No.17所示。
其中，各牛痘病毒加帽酶突变体的氨基酸序列和核苷酸序列如下：
突变位点为V424I的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.3所示，核苷酸序列为SEQ ID No.28所示；
突变位点为Y461F的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.4所示，核苷酸序列为SEQ ID No.29所示；
突变位点为I513V的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.5所示，核苷酸序列为SEQ ID No.30所示；
突变位点为V750L的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.6所示，核苷酸序列为SEQ ID No.31所示；
突变位点为V424I/Y461F的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.7所示，核苷酸序列为SEQ ID No.32所示；
突变位点为V424I/I513V的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.8所示，核苷酸序列为SEQ ID No.33所示；
突变位点为V424I/V750L的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.9所示，核苷酸序列为SEQ ID No.34所示；
突变位点为Y461F/I513V的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.10所示，核苷酸序列为SEQ ID No.35所示；
突变位点为Y461F/V750L的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.11所示，核苷酸序列为SEQ ID No.36所示；
突变位点为I513V/V750L的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.12所示，核苷酸序列为SEQ ID No.37所示；
突变位点为V424I/Y461F/I513V的牛痘病毒加帽酶突变体：氨基酸序列如SEQ IDNo.13所示，核苷酸序列为SEQ ID No.38所示；
突变位点为V424I/Y461F/V750L的牛痘病毒加帽酶突变体：氨基酸序列如SEQ IDNo.14所示，核苷酸序列为SEQ ID No.39所示；
突变位点为Y461F/I513V/V750L的牛痘病毒加帽酶突变体：氨基酸序列如SEQ IDNo.15所示，核苷酸序列为SEQ ID No.40所示；
突变位点为V424I/I513V/V750L的牛痘病毒加帽酶突变体：氨基酸序列如SEQ IDNo.16所示，核苷酸序列为SEQ ID No.41所示；
突变位点为V424I/Y461F/I513V/V750L的牛痘病毒加帽酶突变体：氨基酸序列如SEQ ID No.17所示，核苷酸序列为SEQ ID No.42所示。
测试例1
牛痘病毒加帽酶的酶学性质表征
将野生型牛痘病毒加帽酶以及实施例2提供的多种牛痘病毒加帽酶突变体进行热稳定性测试，按照常规牛痘病毒加帽酶活力测定方法(参见文献DOI:10.1093/nar/gkz751)，具体为：
在一定温度下下孵育酶液，在不同处理时间取样，测定野生型牛痘病毒加帽酶或牛痘病毒加帽酶突变体残余活力百分比，以残余活力百分比的ln值对时间t(min)作图，直线的斜率为失活常数kinact，由t1/2＝ln2/kinact得到该种野生型牛痘病毒加帽酶或牛痘病毒加帽酶突变体在该温度下的半衰期。测定结果详见表1。
表1野生型牛痘病毒加帽酶及其酶突变体的酶学性质表征
从表1可以看出，上述牛痘病毒加帽酶突变体在45℃下的半衰期在35min以上，均长于野生型牛痘病毒加帽酶在45℃下的半衰期，尤其是组合突变体表现出单点突变体热稳定性的叠加效果，特别是发生V424I/Y461F/I513V突变得到的牛痘病毒加帽酶突变体在45℃下的半衰期达103min，是野生型牛痘病毒加帽酶突变体的3倍，具有较好的热稳定性。
综上，本申请所提供的牛痘病毒加帽酶突变体的热稳定性更好，能够在较高的温度下对mRNA加帽时仍然表现出优良的的催化活性，在临床医药、流感疫苗、肿瘤疫苗、生物制药等领域都能发挥重要作用。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
序列表
<110> 苏州瀚源新酶生物科技有限公司
<120> 牛痘病毒加帽酶突变体、重组载体、重组工程菌及其应用
<160> 42
<170> SIPOSequenceListing 1.0
<210> 1
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 1
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttg tagagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tatattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatatca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatagtg gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 2
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 2
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Val Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Tyr Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Ile Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Val Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 3
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 3
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Ile Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Tyr Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Ile Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Val Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 4
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 4
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Val Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Phe Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Ile Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Val Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 5
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 5
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Val Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Tyr Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Val Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Val Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 6
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 6
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Val Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Tyr Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Ile Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Leu Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 7
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 7
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Ile Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Phe Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Ile Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Val Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 8
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 8
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Ile Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Tyr Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Val Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Val Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 9
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 9
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Ile Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Tyr Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Ile Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Leu Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 10
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 10
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Val Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Phe Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Val Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Val Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 11
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 11
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Val Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Phe Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Ile Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Leu Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 12
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 12
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Val Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Tyr Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Val Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Leu Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 13
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 13
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Ile Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Phe Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Val Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Val Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 14
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 14
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Ile Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Phe Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Ile Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Leu Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 15
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 15
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Ile Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Tyr Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Val Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Leu Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 16
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 16
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Val Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Phe Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Val Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Leu Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 17
<211> 844
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 17
Met Asp Ala Asn Val Val Ser Ser Ser Thr Ile Ala Thr Tyr Ile Asp
1 5 10 15
Ala Leu Ala Lys Asn Ala Ser Glu Leu Glu Gln Arg Ser Thr Ala Tyr
20 25 30
Glu Ile Asn Asn Glu Leu Glu Leu Val Phe Ile Lys Pro Pro Leu Ile
35 40 45
Thr Leu Thr Asn Val Val Asn Ile Ser Thr Ile Gln Glu Ser Phe Ile
50 55 60
Arg Phe Thr Val Thr Asn Lys Glu Gly Val Lys Ile Arg Thr Lys Ile
65 70 75 80
Pro Leu Ser Lys Val His Gly Leu Asp Val Lys Asn Val Gln Leu Val
85 90 95
Asp Ala Ile Asp Asn Ile Val Trp Glu Lys Lys Ser Leu Val Thr Glu
100 105 110
Asn Arg Leu His Lys Glu Cys Leu Leu Arg Leu Ser Thr Glu Glu Arg
115 120 125
His Ile Phe Leu Asp Tyr Lys Lys Tyr Gly Ser Ser Ile Arg Leu Glu
130 135 140
Leu Val Asn Leu Ile Gln Ala Lys Thr Lys Asn Phe Thr Ile Asp Phe
145 150 155 160
Lys Leu Lys Tyr Phe Leu Gly Ser Gly Ala Gln Ser Lys Ser Ser Leu
165 170 175
Leu His Ala Ile Asn His Pro Lys Ser Arg Pro Asn Thr Ser Leu Glu
180 185 190
Ile Glu Phe Thr Pro Arg Asp Asn Glu Thr Val Pro Tyr Asp Glu Leu
195 200 205
Ile Lys Glu Leu Thr Thr Leu Ser Arg His Ile Phe Met Ala Ser Pro
210 215 220
Glu Asn Val Ile Leu Ser Pro Pro Ile Asn Ala Pro Ile Lys Thr Phe
225 230 235 240
Met Leu Pro Lys Gln Asp Ile Val Gly Leu Asp Leu Glu Asn Leu Tyr
245 250 255
Ala Val Thr Lys Thr Asp Gly Ile Pro Ile Thr Ile Arg Val Thr Ser
260 265 270
Asn Gly Leu Tyr Cys Tyr Phe Thr His Leu Gly Tyr Ile Ile Arg Tyr
275 280 285
Pro Val Lys Arg Ile Ile Asp Ser Glu Val Val Val Phe Gly Glu Ala
290 295 300
Val Lys Asp Lys Asn Trp Thr Val Tyr Leu Ile Lys Leu Ile Glu Pro
305 310 315 320
Val Asn Ala Ile Asn Asp Arg Leu Glu Glu Ser Lys Tyr Val Glu Ser
325 330 335
Lys Leu Val Asp Ile Cys Asp Arg Ile Val Phe Lys Ser Lys Lys Tyr
340 345 350
Glu Gly Pro Phe Thr Thr Thr Ser Glu Val Val Asp Met Leu Ser Thr
355 360 365
Tyr Leu Pro Lys Gln Pro Glu Gly Val Ile Leu Phe Tyr Ser Lys Gly
370 375 380
Pro Lys Ser Asn Ile Asp Phe Lys Ile Lys Lys Glu Asn Thr Ile Asp
385 390 395 400
Gln Thr Ala Asn Val Val Phe Arg Tyr Met Ser Ser Glu Pro Ile Ile
405 410 415
Phe Gly Glu Ser Ser Ile Phe Ile Glu Tyr Lys Lys Phe Ser Asn Asp
420 425 430
Lys Gly Phe Pro Lys Glu Tyr Gly Ser Gly Lys Ile Val Leu Tyr Asn
435 440 445
Gly Val Asn Tyr Leu Asn Asn Ile Tyr Cys Leu Glu Phe Ile Asn Thr
450 455 460
His Asn Glu Val Gly Ile Lys Ser Val Val Val Pro Ile Lys Phe Ile
465 470 475 480
Ala Glu Phe Leu Val Asn Gly Glu Ile Leu Lys Pro Arg Ile Asp Lys
485 490 495
Thr Met Lys Tyr Ile Asn Ser Glu Asp Tyr Tyr Gly Asn Gln His Asn
500 505 510
Val Ile Val Glu His Leu Arg Asp Gln Ser Ile Lys Ile Gly Asp Ile
515 520 525
Phe Asn Glu Asp Lys Leu Ser Asp Val Gly His Gln Tyr Ala Asn Asn
530 535 540
Asp Lys Phe Arg Leu Asn Pro Glu Val Ser Tyr Phe Thr Asn Lys Arg
545 550 555 560
Thr Arg Gly Pro Leu Gly Ile Leu Ser Asn Tyr Val Lys Thr Leu Leu
565 570 575
Ile Ser Met Tyr Cys Ser Lys Thr Phe Leu Asp Asp Ser Asn Lys Arg
580 585 590
Lys Val Leu Ala Ile Asp Phe Gly Asn Gly Ala Asp Leu Glu Lys Tyr
595 600 605
Phe Tyr Gly Glu Ile Ala Leu Leu Val Ala Thr Asp Pro Asp Ala Asp
610 615 620
Ala Ile Ala Arg Gly Asn Glu Arg Tyr Asn Lys Leu Asn Ser Gly Ile
625 630 635 640
Lys Thr Lys Tyr Tyr Lys Phe Asp Tyr Ile Gln Glu Thr Ile Arg Ser
645 650 655
Asp Thr Phe Val Ser Ser Val Arg Glu Val Phe Tyr Phe Gly Lys Phe
660 665 670
Asn Ile Ile Asp Trp Gln Phe Ala Ile His Tyr Ser Phe His Pro Arg
675 680 685
His Tyr Ala Thr Val Met Asn Asn Leu Ser Glu Leu Thr Ala Ser Gly
690 695 700
Gly Lys Val Leu Ile Thr Thr Met Asp Gly Asp Lys Leu Ser Lys Leu
705 710 715 720
Thr Asp Lys Lys Thr Phe Ile Ile His Lys Asn Leu Pro Ser Ser Glu
725 730 735
Asn Tyr Met Ser Val Glu Lys Ile Ala Asp Asp Arg Ile Leu Val Tyr
740 745 750
Asn Pro Ser Thr Met Ser Thr Pro Met Thr Glu Tyr Ile Ile Lys Lys
755 760 765
Asn Asp Ile Val Arg Val Phe Asn Glu Tyr Gly Phe Val Leu Val Asp
770 775 780
Asn Val Asp Phe Ala Thr Ile Ile Glu Arg Ser Lys Lys Phe Ile Asn
785 790 795 800
Gly Ala Ser Thr Met Glu Asp Arg Pro Ser Thr Arg Asn Phe Phe Glu
805 810 815
Leu Asn Arg Gly Ala Ile Lys Cys Glu Gly Leu Asp Val Glu Asp Leu
820 825 830
Leu Ser Tyr Tyr Val Val Tyr Val Phe Ser Lys Arg
835 840
<210> 18
<211> 31
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 18
cgcatatgat ggatgccaac gtagtatcat c 31
<210> 19
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 19
tcagctctcg agttaccgct tagaaaagac at 32
<210> 20
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 20
tatctttatc gtagagtata agaaatttag ca 32
<210> 21
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 21
actctacgat aaagatagac gactctccaa ag 32
<210> 22
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 22
tttggaattt attaatacac ataatgaagt gg 32
<210> 23
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 23
tattaataaa ttccaaacaa tagatattat tt 32
<210> 24
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 24
acataatgtt atagtcgaac atttaagaga tc 32
<210> 25
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 25
cgactataac attatgttga tttccataat aa 32
<210> 26
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 26
tagaatatta gtatataatc catcaacaat gt 32
<210> 27
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 27
aaaaatagct gatgatagaa tattagtata ta 32
<210> 28
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 28
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatcttta aagagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tatattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatatca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatagtg gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 29
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 29
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttg tagagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tttattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatatca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatagtg gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 30
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 30
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttg tagagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tatattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatgtta tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatagtg gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 31
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 31
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttg tagagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tatattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatatca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatatta gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 32
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 32
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttc tggagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tttattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatatca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatagtg gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 33
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 33
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttc tggagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tatattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatgtta tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatagtg gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 34
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 34
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttc tggagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tatattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatatca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatatta gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 35
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 35
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttg tagagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tttattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatttga tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatagtg gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 36
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 36
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttg tagagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tttattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatatca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatatta gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 37
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 37
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttg tagagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tatattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatgtta tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatatta gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 38
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 38
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttc tggagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tttattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatgtca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatagtg gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 39
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 39
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttc tggagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tttattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatatca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatatta gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 40
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 40
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttg tagagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tttattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatttga tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatatta gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 41
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 41
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttc tggagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tatattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatgtta tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatatta gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
<210> 42
<211> 2535
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 42
atggatgcca acgtagtatc atcttctact attgcgacgt atatagacgc tttagcgaag 60
aatgcttcgg aattagaaca gaggtctacc gcatacgaaa taaataatga attggaacta 120
gtatttatta agccgccatt gattactttg acaaatgtag tgaatatctc tacgattcag 180
gaatcgttta ttcgatttac cgttactaat aaggaaggtg ttaaaattag aactaagatt 240
ccattatcta aggtacatgg tctagatgta aaaaatgtac agttagtaga tgctatagat 300
aacatagttt gggaaaagaa atcattagtg acggaaaatc gtcttcacaa agaatgcttg 360
ttgagactat cgacagagga acgtcatata tttttggatt acaagaaata tggatcctct 420
atccgactag aattagtcaa tcttattcaa gcaaaaacaa aaaactttac gatagacttt 480
aagctaaaat attttctagg atccggtgcc cagtctaaaa gttctttatt acacgctatt 540
aatcatccaa agtcaaggcc taatacatct ctggaaatag aatttacacc tagagacaat 600
gaaacagttc catatgatga actaataaag gaattgacga ctctctcgcg tcatatattt 660
atggcttctc cagagaatgt aattctttct ccgcctatta acgcgcctat aaaaaccttt 720
atgttgccta aacaagatat agtaggtttg gatctggaaa atctatatgc cgtaactaag 780
actgacggca ttcctataac tatcagagtt acatcaaacg ggttgtattg ttattttaca 840
catcttggtt atattattag atatcctgtt aagagaataa tagattccga agtagtagtc 900
tttggtgagg cagttaagga taagaactgg accgtatatc tcattaagct aatagagcct 960
gtgaatgcaa tcaatgatag actagaagaa agtaagtatg ttgaatctaa actagtggat 1020
atttgtgatc ggatagtatt caagtcaaag aaatacgaag gtccgtttac tacaactagt 1080
gaagtcgtcg atatgttatc tacatattta ccaaagcaac cagaaggtgt tattctgttc 1140
tattcaaagg gacctaaatc taacattgat tttaaaatta aaaaggaaaa tactatagac 1200
caaactgcaa atgtagtatt taggtacatg tccagtgaac caattatctt tggagagtcg 1260
tctatctttc tggagtataa gaaatttagc aacgataaag gctttcctaa agaatatggt 1320
tctggtaaga ttgtgttata taacggcgtt aattatctaa ataatatcta ttgtttggaa 1380
tttattaata cacataatga agtgggtatt aagtccgtgg ttgtacctat taagtttata 1440
gcagaattct tagttaatgg agaaatactt aaacctagaa ttgataaaac catgaaatat 1500
attaactcag aagattatta tggaaatcaa cataatgtca tagtcgaaca tttaagagat 1560
caaagcatca aaataggaga tatctttaac gaggataaac tatcggatgt gggacatcaa 1620
tacgccaata atgataaatt tagattaaat ccagaagtta gttattttac gaataaacga 1680
actagaggac cgttgggaat tttatcaaac tacgtcaaga ctcttcttat ttctatgtat 1740
tgttccaaaa catttttaga cgattccaac aaacgaaagg tattggcgat tgattttgga 1800
aacggtgctg acctggaaaa atacttttat ggagagattg cgttattggt agcgacggat 1860
ccggatgctg atgctatagc tagaggaaat gaaagataca acaaattaaa ctctggaatt 1920
aaaaccaagt actacaaatt tgactacatt caggaaacta ttcgatccga tacatttgtc 1980
tctagtgtca gagaagtatt ctattttgga aagtttaata tcatcgactg gcagtttgct 2040
atccattatt cttttcatcc gagacattat gctaccgtca tgaataactt atccgaacta 2100
actgcttctg gaggcaaggt attaatcact accatggacg gagacaaatt atcaaaatta 2160
acagataaaa agacttttat aattcataag aatttaccta gtagcgaaaa ctatatgtct 2220
gtagaaaaaa tagctgatga tagaatatta gtatataatc catcaacaat gtctactcca 2280
atgactgaat acattatcaa aaagaacgat atagtcagag tgtttaacga atacggattt 2340
gttcttgtag ataacgttga tttcgctaca attatagaac gaagtaaaaa gtttattaat 2400
ggcgcatcta caatggaaga tagaccatct acaagaaact ttttcgaact aaatagagga 2460
gccattaaat gtgaaggttt agatgtcgaa gacttactta gttactatgt tgtttatgtc 2520
ttttctaagc ggtaa 2535
Claims (13)
1.一种牛痘病毒加帽酶突变体，其特征在于，所述牛痘病毒加帽酶突变体包括：
(a)、由如SEQ ID No.2所示的氨基酸序列缺失、替代或增加一个或多个氨基酸组成的多肽；或，
(b)、与如SEQ ID No.2所示的氨基酸序列组成的多肽具有至少90％同源性的多肽。
2.根据权利要求1所述的牛痘病毒加帽酶突变体，其特征在于，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列中第424位氨基酸、第461位氨基酸、第513位氨基酸及第750位氨基酸中的至少一个发生突变得到的多肽。
3.根据权利要求2所述的牛痘病毒加帽酶突变体，其特征在于，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列发生V424I突变、Y461F突变、I513V突变及V750L突变中至少一种得到的多肽。
4.根据权利要求3所述的牛痘病毒加帽酶突变体，其特征在于，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列发生V424I突变、Y461F突变、I513V突变、V750L突变中的任意一种得到的多肽；
或者，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变、V750L突变中的任意两种得到的多肽；
或者，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变、V750L突变中的任意三种得到的多肽；
或者，所述牛痘病毒加帽酶突变体包括：由如SEQ ID No.2所示的氨基酸序列同时发生V424I突变、Y461F突变、I513V突变、V750L突变得到的多肽。
5.根据权利要求4所述的牛痘病毒加帽酶突变体，其特征在于，所述牛痘病毒加帽酶突变体的氨基酸序列为如SEQ ID No.3～SEQ ID No.17所示的序列中的一种。
6.根据权利要求1所述的牛痘病毒加帽酶突变体，其特征在于，所述牛痘病毒加帽酶突变体的编码序列包括：
(a)、与如SEQ ID No.1所示的核苷酸序列组成的多核苷酸具有至少90％同源性的多核苷酸；或，
(b)、由如SEQ ID No.1所示的核苷酸序列缺失、替代或增加一个或多个碱基得到的多核苷酸。
7.根据权利要求6所述的牛痘病毒加帽酶突变体，其特征在于，所述牛痘病毒加帽酶突变体的核苷酸序列为如SEQ ID No.28～SEQ ID No.42所示的序列中的一种。
8.根据权利要求1-7任一项所述的牛痘病毒加帽酶突变体，其特征在于，所述牛痘病毒加帽酶突变体为可溶性酶、固定化酶或者基因工程酶。
9.一种重组载体，其特征在于，含有权利要求1-8任一项所述的牛痘病毒加帽酶突变体的编码序列。
10.权利要求9所述的重组载体的制备方法，其特征在于，包括如下步骤：采用第一扩增引物对对第一载体进行PCR扩增，得到重组载体，其中，所述第一载体含有如SEQ ID No.2所示的氨基酸序列对应的编码序列，所述第一扩增引物对含有所述牛痘病毒加帽酶突变体的突变位点对应的核苷酸序列。
11.权利要求10所述的重组载体的制备方法，其特征在于，所述第一扩增引物对选自如下引物对中的至少一对：核苷酸序列如SEQ ID No.20和SEQ ID No.21所示的引物对、核苷酸序列如SEQ ID No.22和SEQ ID No.23所示的引物对、核苷酸序列如SEQ ID No.24和SEQID No.25所示的引物对、核苷酸序列如SEQ ID No.26和SEQ ID No.27所示的引物对。
12.一种重组工程菌，其特征在于，含有权利要求9所述的重组载体。
13.权利要求1-8任一项所述的牛痘病毒加帽酶突变体、权利要求9所述的重组载体或者权利要求12所述的重组工程菌在催化mRNA加帽中的应用。
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