CN113583996B - Bst DNA聚合酶重组突变体、其编码DNA及超快磁珠LAMP检测方法 - Google Patents

Bst DNA聚合酶重组突变体、其编码DNA及超快磁珠LAMP检测方法 Download PDF

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CN113583996B
CN113583996B CN202111146868.9A CN202111146868A CN113583996B CN 113583996 B CN113583996 B CN 113583996B CN 202111146868 A CN202111146868 A CN 202111146868A CN 113583996 B CN113583996 B CN 113583996B
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马海玲
江翱
陈晶晶
柴常升
侯策
曹振
孙晓亮
宋东亮
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Abstract

本发明在野生型Bst DNA聚合酶序列上进行了四个点位的突变，然后将进行点突变后的Bst DNA聚合酶的292‑305的氨基酸替换成DPLPDLIHPRTLRL，在突变后Bst DNA聚合酶序列的C端融合了一个DNA结合蛋白，N端融合了一个HP47多肽序列，在HP47多肽序列前面融合了一个CL7‑SUMO‑Tag，得到Bst DNA聚合酶重组突变体Super‑Bst。Super‑Bst在热稳定性、特异性、链置换能力、延伸能力和逆转录酶活性上得到了显著地提升，能够耐受高盐和各类抑制剂，且可以通过原核表达和亲和纯化大量获得。本发明还公开了其编码DNA，以及一种超快磁珠LAMP检测方法。

Description

Bst DNA聚合酶重组突变体、其编码DNA及超快磁珠LAMP检测 方法
技术领域
本发明专利涉及一种高活性和热稳定性的Bst DNA聚合酶重组突变体、其编码DNA及超快磁珠LAMP检测方法，属于生物技术领域。
背景技术
核酸检测主要分为三种，第一种是高通量测序检测，其优点是检测灵敏度高和检测范围广，但成本高、耗时长、操作复杂。第二种为qPCR检测技术，这种技术具有灵敏度高、耗时短（2-3 h）、成本低和操作简单等特点，成为新冠等疾病检测的主要方法。但qPCR检测技术必须依赖具有荧光检测和可控温功能的实时荧光定量PCR仪，因此这种检测只能在具有该设备的医院或者检测机构进行，并且严重的仪器依赖性限制了大批量样本的检测。尤其是对于需要大规模筛查的疾病（如新冠肺炎），一天可能要进行10万甚至100万接触人群的筛查，使用qPCR检测技术不仅导致检测效率低，而且会导致疾病的恶化和进一步感染。第三种检测方式是环介导等温扩增技术-LAMP(Loop-Mediated IsothermalAmplification)。LAMP技术依赖于识别保守序列DNA的4-6条特异性引物和一种具有链置换功能的DNA聚合酶（如Bst DNA polymerase）在恒温条件下（如60 ℃）处理一小时即可实现对靶分子的109-1010倍扩增。LAMP检测方法具有效率高、耗时短、通量大、不依赖仪器、结果可直接肉眼观察、操作简单等优势，能够同时检测大批量的病理样本，非常适合基层快速诊断，具有巨大的未来市场价值。但是，目前已有的LAMP方法仍然具有两个重要的缺陷：
（1）目前具有链置换功能的Bst DNA聚合酶存在纯化困难、热稳定性差、对高盐和抑制剂的耐受性差、链置换能力弱、产物得率低、延伸能力差等问题；
（2）目前的Bst DNA聚合酶保真性和特异性较差，容易产生非特异性的DNA多聚体；
（3）Bst DNA聚合酶在高温条件下具有的逆转录酶活性较弱，因此在RNA模板检测过程中灵敏度较低；
（4）目前的LAMP检测技术灵敏度还不够强，因此需要使用专业的仪器和试剂对病理学样本进行核酸提取和纯化预处理。
这几个缺陷不仅提高了病理学样本（如强感染性样本）的处理风险，也增加了LAMP检测技术的操作难度，降低了LAMP检测试剂的灵敏度、准确性和稳定性，影响了LAMP检测技术的普及和发展。
发明内容
本发明的目的是提供一种高活性和热稳定性的Bst DNA聚合酶重组突变体，其氨基酸序列如SEQ ID No.2-16中任一项所示。其中效果最佳者为Super-Bst （SEQ ID No.16）。Super-Bst是在野生型Bst DNA聚合酶（https://www.ncbi.nlm.nih.gov/，序列ID：4DSJ_A）序列上进行了Ser358Asp、Thr480Asn、Asp533Glu、Ala539Gly几个点位的突变，然后将进行点突变后的Bst DNA聚合酶的292-305的氨基酸EGLLKVVRPDTKKV替换成DPLPDLIHPRTLRL，在突变后Bst DNA聚合酶序列的C端融合了一个DNA结合蛋白，在突变后Bst DNA聚合酶序列的N端融合了一个HP47多肽序列（SEQ ID No.17），在HP47多肽序列前面融合了一个CL7-SUMO-Tag得到的。HP47多肽序列是能够快速折叠的蛋白结构域，能够有效提高Bst蛋白的稳定性。
本发明还公开了上述高活性和热稳定性的Bst DNA聚合酶重组突变体的编码DNA，其核酸序列如SEQ ID No.35-49所示。SEQ ID No.34为野生型Bst DNA聚合酶的编码核苷酸。
本发明还公开了基于上述Super-Bst的超快磁珠LAMP检测方法，其特征在于其步骤包括：
（1）提取样品中的核酸；
（2）磁珠富集样品中的核酸；
（3）将步骤（2）的磁珠重悬到LAMP反应液中进行扩增，其中LAMP反应液含有上述的Bst DNA聚合酶重组突变体。
优选的，所述LAMP反应液还含有2-20 mM二价金属离子。
优选的，所述二价金属离子为镁离子、锰离子、镉离子、镍离子、锌离子、铜离子、钴离子、钙离子或亚铁离子中的一种或数种。
优选的，所述LAMP反应液还含有5-50 mM Tris、20-200 mM 氯化铵、20-200 mM 氯化钾、1-4 M甜菜碱、0.1-1 mM dNTP。
优选的，Bst DNA聚合酶重组突变体使用浓度为4-40 pmol。
优选的，步骤（1）中采用核酸提取试剂盒进行样品中核酸的提取。
优选的，步骤（2）中的磁珠为RNA结合磁珠。
优选的，步骤（2）中还需要加入磁珠结合缓冲液，所述磁珠结合缓冲液的组分包括4%-40%的聚乙二醇8000、0.2-2 M氯化钠、10-100 mM 三羟甲基氨基甲烷、0.2%-2% TritonX-100和0.2%-2% 吐温20中的一种或多种。
本发明还公开了HP47蛋白结构域，其氨基酸序列如SEQ ID No.17所示。
以及上述HP47蛋白结构域的编码DNA，其核苷酸序列如SEQ ID No.50所示。
本发明提供了高活性和热稳定性的Bst DNA聚合酶重组蛋白突变体（Super-Bst）。与野生型的Bst DNA聚合酶相比，改造后的Super-Bst在热稳定性、特异性、链置换能力、延伸能力和逆转录酶活性上得到了显著地提升，能够耐受高盐和各类抑制剂，且可以通过原核表达和亲和纯化大量获得。此外，本发明还公布了一种基于Super-Bst的超快磁珠LAMP检测技术（Superfast beads-LAMP，简称为SLAMP）。SLAMP检测技术具有灵敏度高（低至一个拷贝的目标核酸分子）、整个检测过程耗时极短（15 min左右）、准确率高、不需要额外的核酸提取步骤、操作简单、安全性好、适用性广和成本低等优势，非常适用于疾病快速诊断领域和家用便携式疾病快速检测产品开发领域。
附图说明
图1 Super-Bst结构和SLAMP技术流程示意图。
图2 Bst结构示意图和突变对Bst结构的影响。
图3 Bst突变体示意图。
图4 Bst突变体延伸能力测试。
图5 Bst突变体保真性测试。
图6 Bst突变体逆转录酶活性测试。
图7 Bst突变体最适反应温度测试。
图8 Bst突变体热稳定性测试。
图9 Bst突变体耐高盐能力测试。
图10 Bst突变体耐硫酸铵能力测试。
图11 Super-Bst经CL7/Im7系统纯化效果。
图12 Super-Bst对二价金属离子偏好性测试。
图13 二价金属离子对Super-Bst保真性影响测试。
图14 Super-Bst与已有Bst DNA聚合酶产品的延伸能力比较。
图15 Super-Bst与已有Bst DNA聚合酶产品的保真性比较。
图16 Super-Bst与已有Bst DNA聚合酶产品的最适反应温度比较。
图17 Super-Bst与已有Bst DNA聚合酶产品的热稳定性比较。
图18 Super-Bst与已有Bst DNA聚合酶产品耐高盐性能比较。
图19 Super-Bst与已有Bst DNA聚合酶产品耐Heparin性能比较。
图20 Super-Bst与已有Bst DNA聚合酶产品耐EDTA性能比较。
图21 Super-Bst与已有Bst DNA聚合酶产品耐苯酚性能比较。
图22 Super-Bst与已有Bst DNA聚合酶产品耐硫酸铵性能比较。
图23 Super-Bst与已有Bst DNA聚合酶产品耐尿素性能比较。
图24 Super-Bst与已有Bst DNA聚合酶产品耐异硫氰酸胍性能比较。
图25 Super-Bst与已有Bst DNA聚合酶产品耐乙醇性能比较。
图26 SLAMP技术原理及流程示意图。
图27 基于不同Bst DNA聚合酶的SLAMP技术在HBV DNA检测上的性能比较。
图28 基于不同Bst DNA聚合酶的SLAMP技术在SARS-CoV-2 RNA检测上的性能比较。
图29 基于Super-Bst DNA聚合酶的SLAMP和LAMP技术在HBV DNA检测上的灵敏度和准确性比较。
图30基于Super-Bst DNA聚合酶的SLAMP和LAMP技术在SARS-CoV-2 RNA检测上的灵敏度和准确性比较。
具体实施方式
通过以下详细说明结合附图可以进一步理解本发明的特点和优点。所提供的实施例仅是对本发明方法的说明，而不以任何方式限制本发明揭示的其余内容。本实施例所使用的探针和引物序列及修饰如表1所示。
表1
Figure 88619DEST_PATH_IMAGE002
实施例1：Bst突变体粗酶性能测试。
在本实施例中，我们根据Bst DNA聚合酶与模板DNA的三维晶体结构（PBD: 4SDJ）挑选了一些保守的活性氨基酸位点进行突变（如图2），并融合了一些增加酶稳定性和延伸能力等性能的功能结构域，重组突变蛋白见图3，图3中的16个蛋白结构自上而下依次对应SEQ ID No.1-16。随后，我们测试了Bst突变体粗酶的性能。具体实施方式如下：
1)Bst突变体原核表达菌株的制备
将合成好的Bst突变体DNA连接到pET-28a载体上，并转化到DH5α大肠杆菌感受态中，涂布到含卡那霉素的LB固体平板上，37℃倒置培养过夜。
挑取状态良好的单克隆菌团于含卡那霉素的LB液体培养基中，37℃，200 rpm/min震荡培养。将菌液进行一代Sanger测序验证。
将测序验证成功的菌株进行质粒抽提，获得pET-28a-Bst突变体表达质粒，并转化到BL21(DE3) 大肠杆菌感受态中，涂布到含卡那霉素的LB固体平板上，37℃倒置培养过夜。
挑取状态良好的单克隆菌团于含卡那霉素的LB液体培养基中，37℃，200 rpm/min震荡培养至OD600值达到0.6。
2)Bst突变体粗酶的获取
按照1：200的接种密度将含pET-28a-Bst突变体表达质粒的BL21(DE3) 大肠杆菌接种至新的含卡那霉素的LB培养基中，37℃震荡培养3 h至OD600值达到0.4。加入终浓度为0.3 mM的IPTG，18℃震荡培养18 h。4000× g，4℃离心收集菌体。用PBS洗涤菌体3次，加入含蛋白酶抑制剂的预冷PBS将菌体重悬至OD600值为6-7（约107cfu/ul），在冰上进行超声破碎（工作5s，停止15s，300T）。12000× g，4℃离心取上清，即为Bst突变体粗酶。
3)Bst突变体性能测试。
将Bst突变体粗酶进行DNA聚合酶延伸能力、保真性、逆转录酶活性、耐热性、耐盐性和耐抑制剂的性能测试。
DNA聚合酶延伸能力和保真性测试：反应体系如表2所示。
表2
组分 用量
M13mp18 Single-stranded DNA（NEB） 10 nM
M13-R 30 nM
10× LAMP buffer 3 ul
粗酶（5 mg/ml） 1 ul
补加DEPC水至 30 ul
10× LAMP buffer：200 mM Tris–HCl pH 8.9, 100 mM (NH4)2SO4, 100 mMKCl, 1% Tween-20, 60 mM MgSO4, 8 M betaine, 3.3 mM dNTPs。
55℃处理10 min后，加入1 ul Exo-I，37℃消化30 min。98℃处理10 min后，加入5ul M270链霉亲和素磁珠进行捕获，捕获获得的DNA使用Swift Biosciences的ACCEL-NGS®1S DNA LIBRARY KITS进行单链DNA建库并测序。
结果如图4和图5所示，Bstm2与Bstm6能够显著增加Bst DNA聚合酶的延伸能力和保真性。这说明Ser358Asp、Thr480Asn、Asp533Glu、Ala539Gly这几个点突变和将292-305的氨基酸EGLLKVVRPDTKKV替换成DPLPDLIHPRTLRL能够显著提升Bst DNA聚合酶的性能。融合Sto7d、Sso7d和DBD等DNA结合域和HP35、HP47等快速折叠结构域能够大幅度提高Bst DNA聚合酶的性能。融合CL7-SUMO tag并不影响Bst DNA聚合酶的性能。
逆转录酶活性测试：反应体系如表3所示。
表3
组分 用量
293细胞总 RNA 1ug
10 uM 18S-R 1 ul
10× LAMP buffer 3 ul
10 mM dNTP 1 ul
粗酶（5 mg/ml） 1 ul
补加DEPC水至 30 ul
55℃处理10 min后98℃处理10 min，将反应后的体系稀释1000倍，使用q18S-F和q18S-R进行荧光定量qPCR分析。
结果如图6所示，Bstm2与Bstm6能够显著增加Bst DNA聚合酶的逆转录酶活性，融合Sto7d、Sso7d和DBD等DNA结合域和HP35、HP47等快速折叠结构域能够大幅度提高Bst DNA聚合酶的逆转录酶性能。融合CL7-SUMO tag并不影响Bst DNA聚合酶的逆转录酶性能。
最适温度、耐热性、耐盐性和耐抑制剂性能测试：
使用HBV LAMP检测Bst突变体耐热性、耐盐性和耐抑制剂性能：反应体系如表4所示。
表4
组分 用量
HBV-F3 0.2 mM
HBV-B3 0.2 mM
HBV-FIP 1.6 mM
HBV-BIP 1.6 mM
HBV-LF 0.8 mM
HBV-LB 0.8 mM
10× LAMP buffer 2.5 ul
HBV DNA （Zymo Research） 1 pg
100× EvaGreen 0.25 ul
粗酶（5 mg/ml） 1 ul
补加DEPC水至 25 ul
65℃孵育60 min，每隔3min检测一次荧光。
结果如图7和图8所示，点突变对Bst DNA聚合酶的最适温度和温度稳定性影响较小。将292-305的氨基酸EGLLKVVRPDTKKV替换成DPLPDLIHPRTLRL能够提高Bst DNA聚合酶的最适温度和温度稳定性。融合Sto7d、Sso7d和DBD等DNA结合域和HP35、HP47等快速折叠结构域能够大幅度提高Bst DNA聚合酶的最适温度和温度稳定性。融合CL7-SUMO tag对Bst DNA聚合酶的的最适温度和温度稳定性影响不大。
结果如图9和图10所示，点突变对Bst DNA聚合酶的耐高盐和耐抑制剂性能影响较小。将292-305的氨基酸EGLLKVVRPDTKKV替换成DPLPDLIHPRTLRL能够提高Bst DNA聚合酶的耐高盐和耐抑制剂性能。融合Sto7d、Sso7d和DBD等DNA结合域和HP35、HP47等快速折叠结构域能够大幅度提高Bst DNA聚合酶的耐高盐和耐抑制剂性能。融合CL7-SUMO tag对Bst DNA聚合酶的的耐高盐和耐抑制剂性能影响不大。
实施例2：Super-Bst的纯化。
在本实施例中，我们公布了Super-Bst纯化具体方案。
1) Super-Bst诱导表达
按照1：200的接种密度将含pET-28a-Bst突变体表达质粒的BL21(DE3) 大肠杆菌接种至新的含卡那霉素的LB培养基中，37℃震荡培养2.5 h至OD600值达到0.3后，于18℃继续震荡培养0.5 h至OD600值达到0.3。加入终浓度为0.3 mM的IPTG，18℃震荡培养18 h。4000× g，4℃离心收集菌体。预冷PBS清洗菌体三次后，称取3 g菌体，加入30 ml 预冷的裂解缓冲液（20 mM Tris-HCl, 500 mM NaCl，5% Glycerol，0.1 mM PMSF，1%蛋白酶抑制剂，pH 8.0）悬浮菌体。在4℃使用高压搅拌仪（~15,000 PSI）处理3 min。4℃，40,000× g 离心20 min后取上清过0.22 um滤膜。
2) 使用CL7-Im7纯化系统纯化Super-Bst
将过滤后的粗酶液孵育到5 ml CL7-Im7填料柱中。4℃条件下，6-8倍体积的高盐缓冲液（20 mM Tris-HCl，2 M NaCl，5% Glycerol）过柱后使用6-8倍体积的无盐缓冲液（20mM Tris-HCl，5% Glycerol）过柱，0.5 ml/min流速，重复4次。加入2倍柱体积的含0.5 mgSUMO蛋白酶的洗脱缓冲液（20 mM Tris-HCl, 50 mM NaCl，5% Glycerol，0.2 mM EDTA），4℃条件下孵育2.5 h。将含Super-Bst的洗脱缓冲液收集透析或超滤，获得高浓度和高纯度的Super-Bst精酶。
纯化结果如图11所示，CL7-Im7纯化系统纯化Super-Bst产量可到达37.5 mg/ml，纯度达到98%以上，能够满足大规模生产需求。
实施例3：二价金属离子对Super-Bst延伸能力和保真性的影响。
在本实施例中，我们验证了二价金属离子对Super-Bst延伸能力和保真性的影响，具体实施方式见实施例1。
结果如图12和图13所示，镁离子、锰离子、钙离子和镉离子等二价金属离子能够显著增强Super-Bst延伸能力和保真性，其中镁离子和锰离子最佳，浓度在4-16 mM时效果最好。
实施例4：Super-Bst与现有Bst DNA聚合酶性能对比。
在本实施例中，我们验证了Super-Bst、Bst（NEB M0275）、WarmStart Bst 2.0 DNAPolymerase（NEB M0538）、Bst 3.0 DNA Polymerase（NEB M0374）和Bst 4.0 DNA/RNA 聚合酶（Haigene A3805）的性能。具体实施方式见实施例1。
结果如图14-图17所示，Super-Bst与已有的Bst DNA聚合酶产品相比具有更强的活性、延伸能力和保真性（图14和 图15），最适温度在75℃左右（图16），高于已有的Bst DNA聚合酶产品（65℃），且Super-Bst具有更好的耐热性（图17）。这些意味着Super-Bst能够在更高的反应温度下进行LAMP反应。Super-Bst具有更高的逆转录，酶活性，这意味着Super-Bst能够更加适用于RT-LAMP中进行RNA的检测。
此外，根据图18-图25的结果我们可以得出，Super-Bst具有更高的耐盐性和耐抑制剂性。包括高浓度氯化钠、硫酸铵、Heparin、EDTA、苯酚、尿素、异硫氰酸胍、乙醇等。这意味着Super-Bst能够适用于更加复杂环境的核酸检测。
实施例5：SLAMP技术流程。
在本实施例中，我们开发了适用于Super-Bst和已有Bst产品的SLAMP技术流程(流程示意图见图1和图26)，并验证了对HBV和SARS-CoV-2假病毒的检测效果。使用的样本为培养的293F细胞中掺入对应浓度的病毒DNA或者RNA。具体实施方式如下：
1)样品失活和裂解：待检测的样本中加入0.5-2倍体积的核酸提取试剂（Lucigen（QE09050）、TIANGEN（KG203）、 Thermo Scientific（78882）或翌圣生物（10184）），95℃处理3-10 min。
2)磁珠富集：加入0.2-1倍体积磁珠结合缓冲液(4%-40%的聚乙二醇8000、0.2-2 M氯化钠、10-100 mM 三羟甲基氨基甲烷、0.2%-2% Triton X-100和0.2%-2% 吐温20)，再加入1/20-1/5的RNA结合磁珠，混匀后室温孵育3-10 min。在磁力架上或者短暂离心去上清。
3)磁珠LAMP反应。加入LAMP反应液充分悬浮磁珠，置于恒温水浴锅或荧光检测PCR仪中反应（Super-Bst反应温度是75℃，其他Bst反应温度是65℃）。
LAMP反应体系如表5所示。
表5
组分 用量
F3 0.2 mM
B3 0.2 mM
FIP 1.6 mM
BIP 1.6 mM
LF 0.8 mM
LB 0.8 mM
10× LAMP buffer 2.5 ul
100× EvaGreen或者HNB 0.25 ul
相关Bst DNA聚合酶 2-20 pmol
补加DEPC水至 25 ul
检测HBV使用表1中HBV 6个引物，检测SARS-CoV-2使用表1中SARS-CoV-2 6个引物。结果如图27和图28所示，SLAMP技术可以有效检测目标DNA和RNA，基于Super-Bst的SLAMP技术比起现有的Bst DNA聚合酶产品在核酸检测上具有耗时短（5 min左右）和特异性高两大优势。
实施例6：SLAMP与LAMP灵敏度和准确性对比。
在本实施例中，我们根据实施例5中的SLAMP流程，验证了基于Super-Bst的SLAMP技术和LAMP技术对不同病毒DNA或RNA拷贝数的检测灵敏度与准确性。
结果如图29和图30所示，SLAMP技术可以检测低至1个拷贝的DNA或RNA分子。相较于LAMP技术，SLAMP技术灵敏度更强，时间更短，特异性和准确性更高。
综上，本发明公布了高活性和热稳定性的Bst DNA聚合酶重组蛋白突变体（Super-Bst）。与已有的Bst DNA聚合酶相比，改造后的Super-Bst在热稳定性、特异性、链置换能力、延伸能力和逆转录酶活性上得到了显著地提升，能够耐受高盐和各类抑制剂，且可以通过原核表达和亲和纯化大量获得。此外，本发明还公布了一种基于Super-Bst的超快磁珠LAMP检测技术（Superfast beads-LAMP，简称为SLAMP）。SLAMP检测技术具有灵敏度高（低至一个拷贝的目标核酸分子）、整个检测过程耗时极短（15 min左右）、准确率高、不需要额外的核酸提取步骤、操作简单、安全性好、适用性广和成本低等优势，非常适用于疾病快速诊断领域和家用便携式疾病快速检测产品开发领域。
序列表
<110> 翌圣生物科技（上海）股份有限公司
<120> Bst DNA聚合酶重组突变体、其编码DNA及超快磁珠LAMP检测方法
<141> 2021-08-13
<160> 50
<170> SIPOSequenceListing 1.0
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<212> PRT
<213> Bacillusstearothermophilus
<400> 1
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Glu Gly Leu Leu Lys Val
290 295 300
Val Arg Pro Asp Thr Lys Lys Val His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Ser Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Thr Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
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Arg Leu Gln Ala His Leu Leu Leu Gln Val His Asp Glu Leu Ile Leu
530 535 540
Glu Ala Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys
580 585
<210> 2
<211> 586
<212> PRT
<213> Artificial Sequence
<400> 2
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Glu Gly Leu Leu Lys Val
290 295 300
Val Arg Pro Asp Thr Lys Lys Val His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
515 520 525
Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu
530 535 540
Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys
580 585
<210> 3
<211> 586
<212> PRT
<213> Artificial Sequence
<400> 3
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Glu Gly Leu Leu Lys Val
290 295 300
Val Arg Pro Asp Thr Lys Lys Val His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Ala Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
515 520 525
Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu
530 535 540
Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys
580 585
<210> 4
<211> 586
<212> PRT
<213> Artificial Sequence
<400> 4
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Glu Gly Leu Leu Lys Val
290 295 300
Val Arg Pro Asp Thr Lys Lys Val His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Asp Arg Gln Ala Lys
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
515 520 525
Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu
530 535 540
Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys
580 585
<210> 5
<211> 586
<212> PRT
<213> Artificial Sequence
<400> 5
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Glu Gly Leu Leu Lys Val
290 295 300
Val Arg Pro Asp Thr Lys Lys Val His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Ala
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
515 520 525
Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu
530 535 540
Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys
580 585
<210> 6
<211> 586
<212> PRT
<213> Artificial Sequence
<400> 6
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Glu Gly Leu Leu Lys Val
290 295 300
Val Arg Pro Asp Thr Lys Lys Val His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Asp Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
515 520 525
Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu
530 535 540
Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys
580 585
<210> 7
<211> 586
<212> PRT
<213> Artificial Sequence
<400> 7
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Asp Pro Leu Pro Asp Leu
290 295 300
Ile His Pro Arg Thr Leu Arg Leu His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
515 520 525
Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu
530 535 540
Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys
580 585
<210> 8
<211> 648
<212> PRT
<213> Artificial Sequence
<400> 8
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Asp Pro Leu Pro Asp Leu
290 295 300
Ile His Pro Arg Thr Leu Arg Leu His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
515 520 525
Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu
530 535 540
Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys Gly Ser Gly Ser Thr Val
580 585 590
Lys Phe Lys Tyr Lys Gly Glu Glu Lys Glu Val Asp Ile Ser Lys Ile
595 600 605
Lys Lys Val Trp Arg Val Gly Lys Met Ile Ser Phe Thr Tyr Asp Asp
610 615 620
Asn Gly Lys Thr Gly Arg Gly Ala Val Ser Glu Lys Asp Ala Pro Lys
625 630 635 640
Glu Leu Leu Gln Met Leu Glu Lys
645
<210> 9
<211> 648
<212> PRT
<213> Artificial Sequence
<400> 9
Met His His His His His His Thr Val Lys Phe Lys Tyr Lys Gly Glu
1 5 10 15
Glu Lys Glu Val Asp Ile Ser Lys Ile Lys Lys Val Trp Arg Val Gly
20 25 30
Lys Met Ile Ser Phe Thr Tyr Asp Asp Asn Gly Lys Thr Gly Arg Gly
35 40 45
Ala Val Ser Glu Lys Asp Ala Pro Lys Glu Leu Leu Gln Met Leu Glu
50 55 60
Lys Gly Ser Gly Ser Lys Met Ala Phe Thr Leu Ala Asp Arg Val Thr
65 70 75 80
Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val Val Glu
85 90 95
Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val Asn Glu
100 105 110
His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp Pro Gln
115 120 125
Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met Phe Asp
130 135 140
Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu Leu Cys
145 150 155 160
Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp Pro Ala
165 170 175
Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln Tyr Glu
180 185 190
Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys Arg Ala
195 200 205
Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys Ala Ala
210 215 220
Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg Arg Asn
225 230 235 240
Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser Ser Ile
245 250 255
Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys Arg Leu
260 265 270
Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val Glu Gln
275 280 285
Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser Pro Lys
290 295 300
Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val Leu Lys
305 310 315 320
Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu Lys Leu
325 330 335
Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg Gln Leu
340 345 350
Gly Lys Leu Gln Ser Thr Tyr Ile Asp Pro Leu Pro Asp Leu Ile His
355 360 365
Pro Arg Thr Leu Arg Leu His Thr Ile Phe Asn Gln Ala Leu Thr Gln
370 375 380
Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile Pro Ile
385 390 395 400
Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro Ser Glu
405 410 415
Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu Leu Arg
420 425 430
Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala Phe Arg
435 440 445
Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe Gln Val
450 455 460
Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys Ala Val
465 470 475 480
Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala Gln Asn
485 490 495
Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg Tyr Phe
500 505 510
Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val Gln Glu
515 520 525
Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg Arg Tyr
530 535 540
Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe Ala Glu
545 550 555 560
Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp Ile Ile
565 570 575
Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu Arg Leu
580 585 590
Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu Glu Gly
595 600 605
Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu Val Met
610 615 620
Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr His Tyr
625 630 635 640
Gly Ser Thr Trp Tyr Asp Ala Lys
645
<210> 10
<211> 649
<212> PRT
<213> Artificial Sequence
<400> 10
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Asp Pro Leu Pro Asp Leu
290 295 300
Ile His Pro Arg Thr Leu Arg Leu His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
515 520 525
Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu
530 535 540
Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys Gly Ser Gly Ser Thr Val
580 585 590
Lys Phe Lys Tyr Lys Gly Glu Glu Lys Glu Val Asp Ile Ser Lys Ile
595 600 605
Lys Lys Val Trp Arg Val Gly Lys Met Ile Ser Phe Thr Tyr Asp Glu
610 615 620
Gly Gly Gly Lys Thr Gly Arg Gly Ala Val Ser Glu Lys Asp Ala Pro
625 630 635 640
Lys Glu Leu Leu Gln Met Leu Glu Lys
645
<210> 11
<211> 649
<212> PRT
<213> Artificial Sequence
<400> 11
Met His His His His His His Thr Val Lys Phe Lys Tyr Lys Gly Glu
1 5 10 15
Glu Lys Glu Val Asp Ile Ser Lys Ile Lys Lys Val Trp Arg Val Gly
20 25 30
Lys Met Ile Ser Phe Thr Tyr Asp Glu Gly Gly Gly Lys Thr Gly Arg
35 40 45
Gly Ala Val Ser Glu Lys Asp Ala Pro Lys Glu Leu Leu Gln Met Leu
50 55 60
Glu Lys Gly Ser Gly Ser Lys Met Ala Phe Thr Leu Ala Asp Arg Val
65 70 75 80
Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val Val
85 90 95
Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val Asn
100 105 110
Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp Pro
115 120 125
Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met Phe
130 135 140
Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu Leu
145 150 155 160
Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp Pro
165 170 175
Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln Tyr
180 185 190
Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys Arg
195 200 205
Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys Ala
210 215 220
Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg Arg
225 230 235 240
Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser Ser
245 250 255
Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys Arg
260 265 270
Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val Glu
275 280 285
Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser Pro
290 295 300
Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val Leu
305 310 315 320
Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu Lys
325 330 335
Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg Gln
340 345 350
Leu Gly Lys Leu Gln Ser Thr Tyr Ile Asp Pro Leu Pro Asp Leu Ile
355 360 365
His Pro Arg Thr Leu Arg Leu His Thr Ile Phe Asn Gln Ala Leu Thr
370 375 380
Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile Pro
385 390 395 400
Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro Ser
405 410 415
Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu Leu
420 425 430
Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala Phe
435 440 445
Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe Gln
450 455 460
Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys Ala
465 470 475 480
Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala Gln
485 490 495
Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg Tyr
500 505 510
Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val Gln
515 520 525
Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg Arg
530 535 540
Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe Ala
545 550 555 560
Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp Ile
565 570 575
Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu Arg
580 585 590
Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu Glu
595 600 605
Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu Val
610 615 620
Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr His
625 630 635 640
Tyr Gly Ser Thr Trp Tyr Asp Ala Lys
645
<210> 12
<211> 657
<212> PRT
<213> Artificial Sequence
<400> 12
Met His His His His His His Lys Met Ala Phe Thr Leu Ala Asp Arg
1 5 10 15
Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val Val Glu Val
20 25 30
Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile Ala Val Val
35 40 45
Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala Leu Ala Asp
50 55 60
Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys Lys Ser Met
65 70 75 80
Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys Gly Ile Glu
85 90 95
Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr Leu Leu Asp
100 105 110
Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys Met Lys Gln
115 120 125
Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys Gly Ala Lys
130 135 140
Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu Val Arg Lys
145 150 155 160
Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp Glu Leu Arg
165 170 175
Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln Pro Leu Ser
180 185 190
Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val Asp Thr Lys
195 200 205
Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu Gly Thr Val
210 215 220
Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn Ile Asn Ser
225 230 235 240
Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln Leu Pro Val
245 250 255
Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp Val Leu Glu
260 265 270
Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu His Tyr Arg
275 280 285
Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Asp Pro Leu Pro Asp Leu
290 295 300
Ile His Pro Arg Thr Leu Arg Leu His Thr Ile Phe Asn Gln Ala Leu
305 310 315 320
Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu Gln Asn Ile
325 330 335
Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala Phe Val Pro
340 345 350
Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp Gln Ile Glu
355 360 365
Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu Met Glu Ala
370 375 380
Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met Asp Ile Phe
385 390 395 400
Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg Gln Ala Lys
405 410 415
Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr Gly Leu Ala
420 425 430
Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe Ile Glu Arg
435 440 445
Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu Asn Ile Val
450 455 460
Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu His Arg Arg
465 470 475 480
Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val Arg Ser Phe
485 490 495
Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser Ala Ala Asp
500 505 510
Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu Lys Glu Glu
515 520 525
Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu Leu Ile Leu
530 535 540
Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu Val Pro Glu
545 550 555 560
Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys Val Asp Tyr
565 570 575
His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys Gly Ser Gly Ser Lys Trp
580 585 590
Asp Gly Thr Arg Ile Val Ala His Leu Ser Gly Gly Val Glu Leu Phe
595 600 605
Asn Arg Lys Met Lys Arg Arg Thr Ala Gln Tyr Pro Glu Val Ala Gly
610 615 620
Thr Leu Ser Asp Val Leu Gly Asp Ser Asp Ala Val Leu Asp Gly Glu
625 630 635 640
Met Ile Thr Leu Ile Gly Gly Lys Pro Ser Phe Gln Gln Leu Met Arg
645 650 655
Arg
<210> 13
<211> 657
<212> PRT
<213> Artificial Sequence
<400> 13
Met His His His His His His Lys Trp Asp Gly Thr Arg Ile Val Ala
1 5 10 15
His Leu Ser Gly Gly Val Glu Leu Phe Asn Arg Lys Met Lys Arg Arg
20 25 30
Thr Ala Gln Tyr Pro Glu Val Ala Gly Thr Leu Ser Asp Val Leu Gly
35 40 45
Asp Ser Asp Ala Val Leu Asp Gly Glu Met Ile Thr Leu Ile Gly Gly
50 55 60
Lys Pro Ser Phe Gln Gln Leu Met Arg Arg Gly Ser Gly Ser Lys Met
65 70 75 80
Ala Phe Thr Leu Ala Asp Arg Val Thr Glu Glu Met Leu Ala Asp Lys
85 90 95
Ala Ala Leu Val Val Glu Val Val Glu Glu Asn Tyr His Asp Ala Pro
100 105 110
Ile Val Gly Ile Ala Val Val Asn Glu His Gly Arg Phe Phe Leu Arg
115 120 125
Pro Glu Thr Ala Leu Ala Asp Pro Gln Phe Val Ala Trp Leu Gly Asp
130 135 140
Glu Thr Lys Lys Lys Ser Met Phe Asp Ser Lys Arg Ala Ala Val Ala
145 150 155 160
Leu Lys Trp Lys Gly Ile Glu Leu Cys Gly Val Ser Phe Asp Leu Leu
165 170 175
Leu Ala Ala Tyr Leu Leu Asp Pro Ala Gln Gly Val Asp Asp Val Ala
180 185 190
Ala Ala Ala Lys Met Lys Gln Tyr Glu Ala Val Arg Pro Asp Glu Ala
195 200 205
Val Tyr Gly Lys Gly Ala Lys Arg Ala Val Pro Asp Glu Pro Val Leu
210 215 220
Ala Glu His Leu Val Arg Lys Ala Ala Ala Ile Trp Glu Leu Glu Arg
225 230 235 240
Pro Phe Leu Asp Glu Leu Arg Arg Asn Glu Gln Asp Arg Leu Leu Val
245 250 255
Glu Leu Glu Gln Pro Leu Ser Ser Ile Leu Ala Glu Met Glu Phe Ala
260 265 270
Gly Val Lys Val Asp Thr Lys Arg Leu Glu Gln Met Gly Lys Glu Leu
275 280 285
Ala Glu Gln Leu Gly Thr Val Glu Gln Arg Ile Tyr Glu Leu Ala Gly
290 295 300
Gln Glu Phe Asn Ile Asn Ser Pro Lys Gln Leu Gly Val Ile Leu Phe
305 310 315 320
Glu Lys Leu Gln Leu Pro Val Leu Lys Lys Thr Lys Thr Gly Tyr Ser
325 330 335
Thr Ser Ala Asp Val Leu Glu Lys Leu Ala Pro Tyr His Glu Ile Val
340 345 350
Glu Asn Ile Leu His Tyr Arg Gln Leu Gly Lys Leu Gln Ser Thr Tyr
355 360 365
Ile Asp Pro Leu Pro Asp Leu Ile His Pro Arg Thr Leu Arg Leu His
370 375 380
Thr Ile Phe Asn Gln Ala Leu Thr Gln Thr Gly Arg Leu Ser Ser Thr
385 390 395 400
Glu Pro Asn Leu Gln Asn Ile Pro Ile Arg Leu Glu Glu Gly Arg Lys
405 410 415
Ile Arg Gln Ala Phe Val Pro Ser Glu Ser Asp Trp Leu Ile Phe Ala
420 425 430
Ala Asp Tyr Asp Gln Ile Glu Leu Arg Val Leu Ala His Ile Ala Glu
435 440 445
Asp Asp Asn Leu Met Glu Ala Phe Arg Arg Asp Leu Asp Ile His Thr
450 455 460
Lys Thr Ala Met Asp Ile Phe Gln Val Ser Glu Asp Glu Val Thr Pro
465 470 475 480
Asn Met Arg Arg Gln Ala Lys Ala Val Asn Phe Gly Ile Val Tyr Gly
485 490 495
Ile Ser Asp Tyr Gly Leu Ala Gln Asn Leu Asn Ile Ser Arg Lys Glu
500 505 510
Ala Ala Glu Phe Ile Glu Arg Tyr Phe Glu Ser Phe Pro Gly Val Lys
515 520 525
Arg Tyr Met Glu Asn Ile Val Gln Glu Ala Lys Gln Lys Gly Tyr Val
530 535 540
Thr Thr Leu Leu His Arg Arg Arg Tyr Leu Pro Asp Ile Asn Ser Arg
545 550 555 560
Asn Phe Asn Val Arg Ser Phe Ala Glu Arg Met Ala Met Asn Thr Pro
565 570 575
Ile Gln Gly Ser Ala Ala Asp Ile Ile Lys Lys Ala Met Ile Asp Leu
580 585 590
Asn Ala Arg Leu Lys Glu Glu Arg Leu Gln Ala His Leu Leu Leu Gln
595 600 605
Val His Glu Glu Leu Ile Leu Glu Gly Pro Lys Glu Glu Met Glu Arg
610 615 620
Leu Cys Arg Leu Val Pro Glu Val Met Glu Gln Ala Val Thr Leu Arg
625 630 635 640
Val Pro Leu Lys Val Asp Tyr His Tyr Gly Ser Thr Trp Tyr Asp Ala
645 650 655
Lys
<210> 14
<211> 687
<212> PRT
<213> Artificial Sequence
<400> 14
Met His His His His His His Pro Arg Gly Val Asp Pro Ser Arg Lys
1 5 10 15
Glu Asn His Leu Ser Asp Glu Asp Phe Lys Ala Val Phe Gly Met Thr
20 25 30
Arg Ser Ala Phe Ala Arg Leu Pro Leu Trp Gly Ser Gly Ser Lys Met
35 40 45
Ala Phe Thr Leu Ala Asp Arg Val Thr Glu Glu Met Leu Ala Asp Lys
50 55 60
Ala Ala Leu Val Val Glu Val Val Glu Glu Asn Tyr His Asp Ala Pro
65 70 75 80
Ile Val Gly Ile Ala Val Val Asn Glu His Gly Arg Phe Phe Leu Arg
85 90 95
Pro Glu Thr Ala Leu Ala Asp Pro Gln Phe Val Ala Trp Leu Gly Asp
100 105 110
Glu Thr Lys Lys Lys Ser Met Phe Asp Ser Lys Arg Ala Ala Val Ala
115 120 125
Leu Lys Trp Lys Gly Ile Glu Leu Cys Gly Val Ser Phe Asp Leu Leu
130 135 140
Leu Ala Ala Tyr Leu Leu Asp Pro Ala Gln Gly Val Asp Asp Val Ala
145 150 155 160
Ala Ala Ala Lys Met Lys Gln Tyr Glu Ala Val Arg Pro Asp Glu Ala
165 170 175
Val Tyr Gly Lys Gly Ala Lys Arg Ala Val Pro Asp Glu Pro Val Leu
180 185 190
Ala Glu His Leu Val Arg Lys Ala Ala Ala Ile Trp Glu Leu Glu Arg
195 200 205
Pro Phe Leu Asp Glu Leu Arg Arg Asn Glu Gln Asp Arg Leu Leu Val
210 215 220
Glu Leu Glu Gln Pro Leu Ser Ser Ile Leu Ala Glu Met Glu Phe Ala
225 230 235 240
Gly Val Lys Val Asp Thr Lys Arg Leu Glu Gln Met Gly Lys Glu Leu
245 250 255
Ala Glu Gln Leu Gly Thr Val Glu Gln Arg Ile Tyr Glu Leu Ala Gly
260 265 270
Gln Glu Phe Asn Ile Asn Ser Pro Lys Gln Leu Gly Val Ile Leu Phe
275 280 285
Glu Lys Leu Gln Leu Pro Val Leu Lys Lys Thr Lys Thr Gly Tyr Ser
290 295 300
Thr Ser Ala Asp Val Leu Glu Lys Leu Ala Pro Tyr His Glu Ile Val
305 310 315 320
Glu Asn Ile Leu His Tyr Arg Gln Leu Gly Lys Leu Gln Ser Thr Tyr
325 330 335
Ile Asp Pro Leu Pro Asp Leu Ile His Pro Arg Thr Leu Arg Leu His
340 345 350
Thr Ile Phe Asn Gln Ala Leu Thr Gln Thr Gly Arg Leu Ser Ser Thr
355 360 365
Glu Pro Asn Leu Gln Asn Ile Pro Ile Arg Leu Glu Glu Gly Arg Lys
370 375 380
Ile Arg Gln Ala Phe Val Pro Ser Glu Ser Asp Trp Leu Ile Phe Ala
385 390 395 400
Ala Asp Tyr Asp Gln Ile Glu Leu Arg Val Leu Ala His Ile Ala Glu
405 410 415
Asp Asp Asn Leu Met Glu Ala Phe Arg Arg Asp Leu Asp Ile His Thr
420 425 430
Lys Thr Ala Met Asp Ile Phe Gln Val Ser Glu Asp Glu Val Thr Pro
435 440 445
Asn Met Arg Arg Gln Ala Lys Ala Val Asn Phe Gly Ile Val Tyr Gly
450 455 460
Ile Ser Asp Tyr Gly Leu Ala Gln Asn Leu Asn Ile Ser Arg Lys Glu
465 470 475 480
Ala Ala Glu Phe Ile Glu Arg Tyr Phe Glu Ser Phe Pro Gly Val Lys
485 490 495
Arg Tyr Met Glu Asn Ile Val Gln Glu Ala Lys Gln Lys Gly Tyr Val
500 505 510
Thr Thr Leu Leu His Arg Arg Arg Tyr Leu Pro Asp Ile Asn Ser Arg
515 520 525
Asn Phe Asn Val Arg Ser Phe Ala Glu Arg Met Ala Met Asn Thr Pro
530 535 540
Ile Gln Gly Ser Ala Ala Asp Ile Ile Lys Lys Ala Met Ile Asp Leu
545 550 555 560
Asn Ala Arg Leu Lys Glu Glu Arg Leu Gln Ala His Leu Leu Leu Gln
565 570 575
Val His Glu Glu Leu Ile Leu Glu Gly Pro Lys Glu Glu Met Glu Arg
580 585 590
Leu Cys Arg Leu Val Pro Glu Val Met Glu Gln Ala Val Thr Leu Arg
595 600 605
Val Pro Leu Lys Val Asp Tyr His Tyr Gly Ser Thr Trp Tyr Asp Ala
610 615 620
Lys Gly Ser Gly Ser Thr Val Lys Phe Lys Tyr Lys Gly Glu Glu Lys
625 630 635 640
Glu Val Asp Ile Ser Lys Ile Lys Lys Val Trp Arg Val Gly Lys Met
645 650 655
Ile Ser Phe Thr Tyr Asp Asp Asn Gly Lys Thr Gly Arg Gly Ala Val
660 665 670
Ser Glu Lys Asp Ala Pro Lys Glu Leu Leu Gln Met Leu Glu Lys
675 680 685
<210> 15
<211> 699
<212> PRT
<213> Artificial Sequence
<400> 15
Met His His His His His His Pro Arg Gly Val Asp Pro Ser Arg Lys
1 5 10 15
Glu Asn His Leu Ser Asp Glu Asp Phe Lys Ala Val Phe Gly Met Thr
20 25 30
Arg Ser Ala Phe Ala Arg Leu Pro Leu Trp Lys Gln Gln Lys Leu Lys
35 40 45
Lys Lys Lys Gly Leu Phe Gly Ser Gly Ser Lys Met Ala Phe Thr Leu
50 55 60
Ala Asp Arg Val Thr Glu Glu Met Leu Ala Asp Lys Ala Ala Leu Val
65 70 75 80
Val Glu Val Val Glu Glu Asn Tyr His Asp Ala Pro Ile Val Gly Ile
85 90 95
Ala Val Val Asn Glu His Gly Arg Phe Phe Leu Arg Pro Glu Thr Ala
100 105 110
Leu Ala Asp Pro Gln Phe Val Ala Trp Leu Gly Asp Glu Thr Lys Lys
115 120 125
Lys Ser Met Phe Asp Ser Lys Arg Ala Ala Val Ala Leu Lys Trp Lys
130 135 140
Gly Ile Glu Leu Cys Gly Val Ser Phe Asp Leu Leu Leu Ala Ala Tyr
145 150 155 160
Leu Leu Asp Pro Ala Gln Gly Val Asp Asp Val Ala Ala Ala Ala Lys
165 170 175
Met Lys Gln Tyr Glu Ala Val Arg Pro Asp Glu Ala Val Tyr Gly Lys
180 185 190
Gly Ala Lys Arg Ala Val Pro Asp Glu Pro Val Leu Ala Glu His Leu
195 200 205
Val Arg Lys Ala Ala Ala Ile Trp Glu Leu Glu Arg Pro Phe Leu Asp
210 215 220
Glu Leu Arg Arg Asn Glu Gln Asp Arg Leu Leu Val Glu Leu Glu Gln
225 230 235 240
Pro Leu Ser Ser Ile Leu Ala Glu Met Glu Phe Ala Gly Val Lys Val
245 250 255
Asp Thr Lys Arg Leu Glu Gln Met Gly Lys Glu Leu Ala Glu Gln Leu
260 265 270
Gly Thr Val Glu Gln Arg Ile Tyr Glu Leu Ala Gly Gln Glu Phe Asn
275 280 285
Ile Asn Ser Pro Lys Gln Leu Gly Val Ile Leu Phe Glu Lys Leu Gln
290 295 300
Leu Pro Val Leu Lys Lys Thr Lys Thr Gly Tyr Ser Thr Ser Ala Asp
305 310 315 320
Val Leu Glu Lys Leu Ala Pro Tyr His Glu Ile Val Glu Asn Ile Leu
325 330 335
His Tyr Arg Gln Leu Gly Lys Leu Gln Ser Thr Tyr Ile Asp Pro Leu
340 345 350
Pro Asp Leu Ile His Pro Arg Thr Leu Arg Leu His Thr Ile Phe Asn
355 360 365
Gln Ala Leu Thr Gln Thr Gly Arg Leu Ser Ser Thr Glu Pro Asn Leu
370 375 380
Gln Asn Ile Pro Ile Arg Leu Glu Glu Gly Arg Lys Ile Arg Gln Ala
385 390 395 400
Phe Val Pro Ser Glu Ser Asp Trp Leu Ile Phe Ala Ala Asp Tyr Asp
405 410 415
Gln Ile Glu Leu Arg Val Leu Ala His Ile Ala Glu Asp Asp Asn Leu
420 425 430
Met Glu Ala Phe Arg Arg Asp Leu Asp Ile His Thr Lys Thr Ala Met
435 440 445
Asp Ile Phe Gln Val Ser Glu Asp Glu Val Thr Pro Asn Met Arg Arg
450 455 460
Gln Ala Lys Ala Val Asn Phe Gly Ile Val Tyr Gly Ile Ser Asp Tyr
465 470 475 480
Gly Leu Ala Gln Asn Leu Asn Ile Ser Arg Lys Glu Ala Ala Glu Phe
485 490 495
Ile Glu Arg Tyr Phe Glu Ser Phe Pro Gly Val Lys Arg Tyr Met Glu
500 505 510
Asn Ile Val Gln Glu Ala Lys Gln Lys Gly Tyr Val Thr Thr Leu Leu
515 520 525
His Arg Arg Arg Tyr Leu Pro Asp Ile Asn Ser Arg Asn Phe Asn Val
530 535 540
Arg Ser Phe Ala Glu Arg Met Ala Met Asn Thr Pro Ile Gln Gly Ser
545 550 555 560
Ala Ala Asp Ile Ile Lys Lys Ala Met Ile Asp Leu Asn Ala Arg Leu
565 570 575
Lys Glu Glu Arg Leu Gln Ala His Leu Leu Leu Gln Val His Glu Glu
580 585 590
Leu Ile Leu Glu Gly Pro Lys Glu Glu Met Glu Arg Leu Cys Arg Leu
595 600 605
Val Pro Glu Val Met Glu Gln Ala Val Thr Leu Arg Val Pro Leu Lys
610 615 620
Val Asp Tyr His Tyr Gly Ser Thr Trp Tyr Asp Ala Lys Gly Ser Gly
625 630 635 640
Ser Thr Val Lys Phe Lys Tyr Lys Gly Glu Glu Lys Glu Val Asp Ile
645 650 655
Ser Lys Ile Lys Lys Val Trp Arg Val Gly Lys Met Ile Ser Phe Thr
660 665 670
Tyr Asp Asp Asn Gly Lys Thr Gly Arg Gly Ala Val Ser Glu Lys Asp
675 680 685
Ala Pro Lys Glu Leu Leu Gln Met Leu Glu Lys
690 695
<210> 16
<211> 928
<212> PRT
<213> Artificial Sequence
<400> 16
Met Ser Lys Ser Asn Glu Pro Gly Lys Ala Thr Gly Glu Gly Lys Pro
1 5 10 15
Val Asn Asn Lys Trp Leu Asn Asn Ala Gly Lys Asp Leu Gly Ser Pro
20 25 30
Val Pro Asp Arg Ile Ala Asn Lys Leu Arg Asp Lys Glu Phe Glu Ser
35 40 45
Phe Asp Asp Phe Arg Glu Thr Phe Trp Glu Glu Val Ser Lys Asp Pro
50 55 60
Glu Leu Ser Lys Gln Phe Ser Arg Asn Asn Asn Asp Arg Met Lys Val
65 70 75 80
Gly Lys Ala Pro Lys Thr Arg Thr Gln Asp Val Ser Gly Lys Arg Thr
85 90 95
Ser Phe Glu Leu Asn His Gln Lys Pro Ile Glu Gln Asn Gly Gly Val
100 105 110
Tyr Asp Met Asp Asn Ile Ser Val Val Thr Pro Lys Arg Asn Ile Asp
115 120 125
Ile Glu Gly Gly Ser Gly Ser Ser Asp Ser Glu Val Asn Gln Glu Ala
130 135 140
Lys Pro Glu Val Lys Pro Glu Val Lys Pro Glu Thr His Ile Asn Leu
145 150 155 160
Lys Val Ser Asp Gly Ser Ser Glu Ile Phe Phe Lys Ile Lys Lys Thr
165 170 175
Thr Pro Leu Arg Arg Leu Met Glu Ala Phe Ala Lys Arg Gln Gly Lys
180 185 190
Glu Met Asp Ser Leu Arg Phe Leu Tyr Asp Gly Ile Arg Ile Gln Ala
195 200 205
Asp Gln Thr Pro Glu Asp Leu Asp Met Glu Asp Asn Asp Ile Ile Glu
210 215 220
Ala His Arg Glu Gln Ile Gly Gly Gly Ser Gly Ser Pro Arg Gly Val
225 230 235 240
Asp Pro Ser Arg Lys Glu Asn His Leu Ser Asp Glu Asp Phe Lys Ala
245 250 255
Val Phe Gly Met Thr Arg Ser Ala Phe Ala Arg Leu Pro Leu Trp Lys
260 265 270
Gln Gln Lys Leu Lys Lys Lys Lys Gly Leu Phe Gly Ser Gly Ser Lys
275 280 285
Met Ala Phe Thr Leu Ala Asp Arg Val Thr Glu Glu Met Leu Ala Asp
290 295 300
Lys Ala Ala Leu Val Val Glu Val Val Glu Glu Asn Tyr His Asp Ala
305 310 315 320
Pro Ile Val Gly Ile Ala Val Val Asn Glu His Gly Arg Phe Phe Leu
325 330 335
Arg Pro Glu Thr Ala Leu Ala Asp Pro Gln Phe Val Ala Trp Leu Gly
340 345 350
Asp Glu Thr Lys Lys Lys Ser Met Phe Asp Ser Lys Arg Ala Ala Val
355 360 365
Ala Leu Lys Trp Lys Gly Ile Glu Leu Cys Gly Val Ser Phe Asp Leu
370 375 380
Leu Leu Ala Ala Tyr Leu Leu Asp Pro Ala Gln Gly Val Asp Asp Val
385 390 395 400
Ala Ala Ala Ala Lys Met Lys Gln Tyr Glu Ala Val Arg Pro Asp Glu
405 410 415
Ala Val Tyr Gly Lys Gly Ala Lys Arg Ala Val Pro Asp Glu Pro Val
420 425 430
Leu Ala Glu His Leu Val Arg Lys Ala Ala Ala Ile Trp Glu Leu Glu
435 440 445
Arg Pro Phe Leu Asp Glu Leu Arg Arg Asn Glu Gln Asp Arg Leu Leu
450 455 460
Val Glu Leu Glu Gln Pro Leu Ser Ser Ile Leu Ala Glu Met Glu Phe
465 470 475 480
Ala Gly Val Lys Val Asp Thr Lys Arg Leu Glu Gln Met Gly Lys Glu
485 490 495
Leu Ala Glu Gln Leu Gly Thr Val Glu Gln Arg Ile Tyr Glu Leu Ala
500 505 510
Gly Gln Glu Phe Asn Ile Asn Ser Pro Lys Gln Leu Gly Val Ile Leu
515 520 525
Phe Glu Lys Leu Gln Leu Pro Val Leu Lys Lys Thr Lys Thr Gly Tyr
530 535 540
Ser Thr Ser Ala Asp Val Leu Glu Lys Leu Ala Pro Tyr His Glu Ile
545 550 555 560
Val Glu Asn Ile Leu His Tyr Arg Gln Leu Gly Lys Leu Gln Ser Thr
565 570 575
Tyr Ile Asp Pro Leu Pro Asp Leu Ile His Pro Arg Thr Leu Arg Leu
580 585 590
His Thr Ile Phe Asn Gln Ala Leu Thr Gln Thr Gly Arg Leu Ser Ser
595 600 605
Thr Glu Pro Asn Leu Gln Asn Ile Pro Ile Arg Leu Glu Glu Gly Arg
610 615 620
Lys Ile Arg Gln Ala Phe Val Pro Ser Glu Ser Asp Trp Leu Ile Phe
625 630 635 640
Ala Ala Asp Tyr Asp Gln Ile Glu Leu Arg Val Leu Ala His Ile Ala
645 650 655
Glu Asp Asp Asn Leu Met Glu Ala Phe Arg Arg Asp Leu Asp Ile His
660 665 670
Thr Lys Thr Ala Met Asp Ile Phe Gln Val Ser Glu Asp Glu Val Thr
675 680 685
Pro Asn Met Arg Arg Gln Ala Lys Ala Val Asn Phe Gly Ile Val Tyr
690 695 700
Gly Ile Ser Asp Tyr Gly Leu Ala Gln Asn Leu Asn Ile Ser Arg Lys
705 710 715 720
Glu Ala Ala Glu Phe Ile Glu Arg Tyr Phe Glu Ser Phe Pro Gly Val
725 730 735
Lys Arg Tyr Met Glu Asn Ile Val Gln Glu Ala Lys Gln Lys Gly Tyr
740 745 750
Val Thr Thr Leu Leu His Arg Arg Arg Tyr Leu Pro Asp Ile Asn Ser
755 760 765
Arg Asn Phe Asn Val Arg Ser Phe Ala Glu Arg Met Ala Met Asn Thr
770 775 780
Pro Ile Gln Gly Ser Ala Ala Asp Ile Ile Lys Lys Ala Met Ile Asp
785 790 795 800
Leu Asn Ala Arg Leu Lys Glu Glu Arg Leu Gln Ala His Leu Leu Leu
805 810 815
Gln Val His Glu Glu Leu Ile Leu Glu Gly Pro Lys Glu Glu Met Glu
820 825 830
Arg Leu Cys Arg Leu Val Pro Glu Val Met Glu Gln Ala Val Thr Leu
835 840 845
Arg Val Pro Leu Lys Val Asp Tyr His Tyr Gly Ser Thr Trp Tyr Asp
850 855 860
Ala Lys Gly Ser Gly Ser Thr Val Lys Phe Lys Tyr Lys Gly Glu Glu
865 870 875 880
Lys Glu Val Asp Ile Ser Lys Ile Lys Lys Val Trp Arg Val Gly Lys
885 890 895
Met Ile Ser Phe Thr Tyr Asp Asp Asn Gly Lys Thr Gly Arg Gly Ala
900 905 910
Val Ser Glu Lys Asp Ala Pro Lys Glu Leu Leu Gln Met Leu Glu Lys
915 920 925
<210> 17
<211> 47
<212> PRT
<213> Artificial Sequence
<400> 17
Pro Arg Gly Val Asp Pro Ser Arg Lys Glu Asn His Leu Ser Asp Glu
1 5 10 15
Asp Phe Lys Ala Val Phe Gly Met Thr Arg Ser Ala Phe Ala Arg Leu
20 25 30
Pro Leu Trp Lys Gln Gln Lys Leu Lys Lys Lys Lys Gly Leu Phe
35 40 45
<210> 18
<211> 19
<212> DNA
<213> Artificial Sequence
<400> 18
cacgacgttg taaaacgac 19
<210> 19
<211> 28
<212> DNA
<213> Artificial Sequence
<400> 19
taatgatcct tccgcaggtt cacctacg 28
<210> 20
<211> 21
<212> DNA
<213> Artificial Sequence
<400> 20
gttttcggaa ctgaggccat g 21
<210> 21
<211> 21
<212> DNA
<213> Artificial Sequence
<400> 21
tcggaactac gacggtatct g 21
<210> 22
<211> 19
<212> DNA
<213> Artificial Sequence
<400> 22
tcaaccccat caaggacca 19
<210> 23
<211> 20
<212> DNA
<213> Artificial Sequence
<400> 23
gcctgaggat gactgtctct 20
<210> 24
<211> 39
<212> DNA
<213> Artificial Sequence
<400> 24
ccaaaacacc gccgtgtgga agccaaccag gtaggagtg 39
<210> 25
<211> 39
<212> DNA
<213> Artificial Sequence
<400> 25
caggctcagg gcatgttgac ctaggctgcc ttcctgact 39
<210> 26
<211> 19
<212> DNA
<213> Artificial Sequence
<400> 26
aaccctggcc cgaatgctc 19
<210> 27
<211> 22
<212> DNA
<213> Artificial Sequence
<400> 27
gtcaacaatt cctcctcctg cc 22
<210> 28
<211> 18
<212> DNA
<213> Artificial Sequence
<400> 28
cggtggacaa attgtcac 18
<210> 29
<211> 22
<212> DNA
<213> Artificial Sequence
<400> 29
cttctctgga tttaacacac tt 22
<210> 30
<211> 47
<212> DNA
<213> Artificial Sequence
<400> 30
tcagcacaca aagccaaaaa tttatctgtg caaaggaaat taaggag 47
<210> 31
<211> 45
<212> DNA
<213> Artificial Sequence
<400> 31
tattggtgga gctaaactta aagccctgta caatcccttt gagtg 45
<210> 32
<211> 28
<212> DNA
<213> Artificial Sequence
<400> 32
ttacaagctt aaagaatgtc tgaacact 28
<210> 33
<211> 27
<212> DNA
<213> Artificial Sequence
<400> 33
ttgaatttag gtgaaacatt tgtcacg 27
<210> 34
<211> 1758
<212> DNA
<213> Artificial Sequence
<400> 34
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgaaggt 900
ctgctgaaag tggtgcgtcc ggacaccaaa aaagtccata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt actctcagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccaaagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattac ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgat 1620
gagctgattc tggaagcgcc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaa 1758
<210> 35
<211> 1758
<212> DNA
<213> Artificial Sequence
<400> 35
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgaaggt 900
ctgctgaaag tggtgcgtcc ggacaccaaa aaagtccata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccaaagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 1620
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaa 1758
<210> 36
<211> 1758
<212> DNA
<213> Artificial Sequence
<400> 36
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgaaggt 900
ctgctgaaag tggtgcgtcc ggacaccaaa aaagtccata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggctgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccaaagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 1620
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaa 1758
<210> 37
<211> 1758
<212> DNA
<213> Artificial Sequence
<400> 37
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgaaggt 900
ctgctgaaag tggtgcgtcc ggacaccaaa aaagtccata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atggaccgtc aggccaaagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 1620
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaa 1758
<210> 38
<211> 1758
<212> DNA
<213> Artificial Sequence
<400> 38
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgaaggt 900
ctgctgaaag tggtgcgtcc ggacaccaaa aaagtccata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccgcagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 1620
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaa 1758
<210> 39
<211> 1758
<212> DNA
<213> Artificial Sequence
<400> 39
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgaaggt 900
ctgctgaaag tggtgcgtcc ggacaccaaa aaagtccata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccaaagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga tcgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 1620
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaa 1758
<210> 40
<211> 1758
<212> DNA
<213> Artificial Sequence
<400> 40
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgatccg 900
ctgccggacc tgatccaccc gcgtaccctg cgtctgcata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccaaagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 1620
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaa 1758
<210> 41
<211> 1944
<212> DNA
<213> Artificial Sequence
<400> 41
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgatccg 900
ctgccggacc tgatccaccc gcgtaccctg cgtctgcata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccaaagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 1620
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaagg cagcggctct accgtgaaat tcaaatacaa aggcgaagag 1800
aaggaggttg acatctctaa aatcaaaaaa gtctggcgtg ttggtaaaat gatctccttc 1860
acctacgacg acaacggtaa aaccggccgt ggtgctgtct ctgaaaagga tgcaccgaaa 1920
gaactgctgc agatgctgga aaaa 1944
<210> 42
<211> 1944
<212> DNA
<213> Artificial Sequence
<400> 42
atgcaccacc accaccatca taccgtgaaa ttcaaataca aaggcgaaga gaaggaggtt 60
gacatctcta aaatcaaaaa agtctggcgt gttggtaaaa tgatctcctt cacctacgac 120
gacaacggta aaaccggccg tggtgctgtc tctgaaaagg atgcaccgaa agaactgctg 180
cagatgctgg aaaaaggcag cggctctaaa atggcgttta ccctggctga ccgcgtgacc 240
gaggagatgc tggcagacaa agcagctctg gtggtggaag ttgttgaaga aaactaccat 300
gacgcaccaa tcgttggcat cgcagttgtt aacgaacatg gccgtttctt tctgcgtccg 360
gaaactgcgc tggcagatcc gcaattcgtc gcttggctgg gtgacgaaac taaaaaaaaa 420
agcatgttcg attccaaacg tgccgcggta gctctgaaat ggaaaggcat cgaactgtgc 480
ggcgttagct tcgacctgct gctggctgct tatctgctgg atcctgcgca gggcgttgac 540
gacgtagcag cagctgcaaa aatgaagcag tacgaagcag ttcgtccaga cgaagccgtt 600
tacggcaaag gtgcaaaacg tgcggttcca gacgaaccgg ttctggcgga acacctggtt 660
cgcaaagccg ctgctatctg ggaactggaa cgcccgttcc tggatgaact gcgtcgtaac 720
gaacaagatc gtctgctggt cgaactggaa cagccgctgt ctagcattct ggctgaaatg 780
gaatttgcgg gcgttaaagt agacactaaa cgtctggaac agatgggcaa agaactggca 840
gaacagctgg gtactgttga acagcgtatc tacgaactgg cgggccagga attcaacatc 900
aactctccga agcagctggg cgttattctg ttcgaaaaac tgcaactgcc ggtgctgaaa 960
aaaactaaaa ccggttactc caccagcgct gacgtactgg agaagctggc cccataccat 1020
gaaattgttg aaaacattct gcactatcgt cagctgggca aactgcagtc tacttatatc 1080
gatccgctgc cggacctgat ccacccgcgt accctgcgtc tgcataccat cttcaaccag 1140
gcgctgaccc agaccggtcg tctgtcttct accgagccga acctgcagaa catcccgatc 1200
cgtctggaag aaggtcgtaa aatccgtcag gctttcgttc cgagcgaatc tgactggctg 1260
atcttcgctg cggattacga ccagattgaa ctgcgtgtgc tggctcacat cgctgaggat 1320
gacaatctga tggaagcttt ccgccgtgat ctggacatcc acaccaaaac tgcgatggat 1380
atcttccaag ttagcgaaga cgaggttact ccgaacatgc gccgtcaggc caaagctgtc 1440
aactttggca tcgtctacgg tatttccgac tacggcctgg cacagaacct gaatatctct 1500
cgcaaagaag ccgcggaatt catcgaacgt tatttcgaat ccttcccggg tgtaaaacgt 1560
tacatggaga acatcgtcca ggaagctaag cagaaaggct atgtaactac tctgctgcat 1620
cgtcgccgtt acctgcctga tattaactct cgtaacttca acgtgcgttc tttcgctgaa 1680
cgcatggcga tgaacactcc aatccaaggt tctgcggcgg acatcattaa aaaggcaatg 1740
attgatctga atgcccgtct gaaagaagag cgtctgcagg ctcacctgct gctgcaggtg 1800
cacgaggagc tgattctgga aggaccgaaa gaagaaatgg aacgcctgtg tcgtctggtg 1860
ccggaggtta tggaacaggc ggttacgctg cgcgtaccgc tgaaagtaga ctaccactac 1920
ggttctactt ggtacgacgc caaa 1944
<210> 43
<211> 1947
<212> DNA
<213> Artificial Sequence
<400> 43
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgatccg 900
ctgccggacc tgatccaccc gcgtaccctg cgtctgcata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccaaagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 1620
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaagg cagcggctct accgttaaat tcaaatacaa aggcgaagaa 1800
aaagaggttg acattagcaa aatcaaaaaa gtttggcgtg tgggtaaaat gatctccttt 1860
acttatgatg aaggcggtgg caaaactggc cgtggtgcgg tcagcgaaaa agatgcccct 1920
aaagaactgc tgcagatgct ggaaaaa 1947
<210> 44
<211> 1947
<212> DNA
<213> Artificial Sequence
<400> 44
atgcaccacc accaccatca taccgttaaa ttcaaataca aaggcgaaga aaaagaggtt 60
gacattagca aaatcaaaaa agtttggcgt gtgggtaaaa tgatctcctt tacttatgat 120
gaaggcggtg gcaaaactgg ccgtggtgcg gtcagcgaaa aagatgcccc taaagaactg 180
ctgcagatgc tggaaaaagg cagcggctct aaaatggcgt ttaccctggc tgaccgcgtg 240
accgaggaga tgctggcaga caaagcagct ctggtggtgg aagttgttga agaaaactac 300
catgacgcac caatcgttgg catcgcagtt gttaacgaac atggccgttt ctttctgcgt 360
ccggaaactg cgctggcaga tccgcaattc gtcgcttggc tgggtgacga aactaaaaaa 420
aaaagcatgt tcgattccaa acgtgccgcg gtagctctga aatggaaagg catcgaactg 480
tgcggcgtta gcttcgacct gctgctggct gcttatctgc tggatcctgc gcagggcgtt 540
gacgacgtag cagcagctgc aaaaatgaag cagtacgaag cagttcgtcc agacgaagcc 600
gtttacggca aaggtgcaaa acgtgcggtt ccagacgaac cggttctggc ggaacacctg 660
gttcgcaaag ccgctgctat ctgggaactg gaacgcccgt tcctggatga actgcgtcgt 720
aacgaacaag atcgtctgct ggtcgaactg gaacagccgc tgtctagcat tctggctgaa 780
atggaatttg cgggcgttaa agtagacact aaacgtctgg aacagatggg caaagaactg 840
gcagaacagc tgggtactgt tgaacagcgt atctacgaac tggcgggcca ggaattcaac 900
atcaactctc cgaagcagct gggcgttatt ctgttcgaaa aactgcaact gccggtgctg 960
aaaaaaacta aaaccggtta ctccaccagc gctgacgtac tggagaagct ggccccatac 1020
catgaaattg ttgaaaacat tctgcactat cgtcagctgg gcaaactgca gtctacttat 1080
atcgatccgc tgccggacct gatccacccg cgtaccctgc gtctgcatac catcttcaac 1140
caggcgctga cccagaccgg tcgtctgtct tctaccgagc cgaacctgca gaacatcccg 1200
atccgtctgg aagaaggtcg taaaatccgt caggctttcg ttccgagcga atctgactgg 1260
ctgatcttcg ctgcggatta cgaccagatt gaactgcgtg tgctggctca catcgctgag 1320
gatgacaatc tgatggaagc tttccgccgt gatctggaca tccacaccaa aactgcgatg 1380
gatatcttcc aagttagcga agacgaggtt actccgaaca tgcgccgtca ggccaaagct 1440
gtcaactttg gcatcgtcta cggtatttcc gactacggcc tggcacagaa cctgaatatc 1500
tctcgcaaag aagccgcgga attcatcgaa cgttatttcg aatccttccc gggtgtaaaa 1560
cgttacatgg agaacatcgt ccaggaagct aagcagaaag gctatgtaac tactctgctg 1620
catcgtcgcc gttacctgcc tgatattaac tctcgtaact tcaacgtgcg ttctttcgct 1680
gaacgcatgg cgatgaacac tccaatccaa ggttctgcgg cggacatcat taaaaaggca 1740
atgattgatc tgaatgcccg tctgaaagaa gagcgtctgc aggctcacct gctgctgcag 1800
gtgcacgagg agctgattct ggaaggaccg aaagaagaaa tggaacgcct gtgtcgtctg 1860
gtgccggagg ttatggaaca ggcggttacg ctgcgcgtac cgctgaaagt agactaccac 1920
tacggttcta cttggtacga cgccaaa 1947
<210> 45
<211> 1971
<212> DNA
<213> Artificial Sequence
<400> 45
atgcaccacc accaccatca taaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 60
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 120
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 180
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 240
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 300
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 360
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 420
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 480
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 540
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 600
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 660
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 720
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 780
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 840
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgatccg 900
ctgccggacc tgatccaccc gcgtaccctg cgtctgcata ccatcttcaa ccaggcgctg 960
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1020
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1080
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1140
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 1200
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccaaagc tgtcaacttt 1260
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 1320
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 1380
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 1440
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 1500
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 1560
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 1620
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 1680
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 1740
acttggtacg acgccaaagg cagcggctct aaatgggatg gtacccgtat cgtcgcacac 1800
ctgtctggtg gtgttgaact gttcaaccgt aagatgaaac gtcgtactgc acagtatccg 1860
gaagtagcgg gtaccctgtc cgatgtgctg ggcgatagcg atgcggttct ggacggcgaa 1920
atgatcactc tgattggtgg caaaccgagc ttccaacagc tgatgcgccg t 1971
<210> 46
<211> 1971
<212> DNA
<213> Artificial Sequence
<400> 46
atgcaccacc accaccatca taaatgggat ggtacccgta tcgtcgcaca cctgtctggt 60
ggtgttgaac tgttcaaccg taagatgaaa cgtcgtactg cacagtatcc ggaagtagcg 120
ggtaccctgt ccgatgtgct gggcgatagc gatgcggttc tggacggcga aatgatcact 180
ctgattggtg gcaaaccgag cttccaacag ctgatgcgcc gtggcagcgg ctctaaaatg 240
gcgtttaccc tggctgaccg cgtgaccgag gagatgctgg cagacaaagc agctctggtg 300
gtggaagttg ttgaagaaaa ctaccatgac gcaccaatcg ttggcatcgc agttgttaac 360
gaacatggcc gtttctttct gcgtccggaa actgcgctgg cagatccgca attcgtcgct 420
tggctgggtg acgaaactaa aaaaaaaagc atgttcgatt ccaaacgtgc cgcggtagct 480
ctgaaatgga aaggcatcga actgtgcggc gttagcttcg acctgctgct ggctgcttat 540
ctgctggatc ctgcgcaggg cgttgacgac gtagcagcag ctgcaaaaat gaagcagtac 600
gaagcagttc gtccagacga agccgtttac ggcaaaggtg caaaacgtgc ggttccagac 660
gaaccggttc tggcggaaca cctggttcgc aaagccgctg ctatctggga actggaacgc 720
ccgttcctgg atgaactgcg tcgtaacgaa caagatcgtc tgctggtcga actggaacag 780
ccgctgtcta gcattctggc tgaaatggaa tttgcgggcg ttaaagtaga cactaaacgt 840
ctggaacaga tgggcaaaga actggcagaa cagctgggta ctgttgaaca gcgtatctac 900
gaactggcgg gccaggaatt caacatcaac tctccgaagc agctgggcgt tattctgttc 960
gaaaaactgc aactgccggt gctgaaaaaa actaaaaccg gttactccac cagcgctgac 1020
gtactggaga agctggcccc ataccatgaa attgttgaaa acattctgca ctatcgtcag 1080
ctgggcaaac tgcagtctac ttatatcgat ccgctgccgg acctgatcca cccgcgtacc 1140
ctgcgtctgc ataccatctt caaccaggcg ctgacccaga ccggtcgtct gtcttctacc 1200
gagccgaacc tgcagaacat cccgatccgt ctggaagaag gtcgtaaaat ccgtcaggct 1260
ttcgttccga gcgaatctga ctggctgatc ttcgctgcgg attacgacca gattgaactg 1320
cgtgtgctgg ctcacatcgc tgaggatgac aatctgatgg aagctttccg ccgtgatctg 1380
gacatccaca ccaaaactgc gatggatatc ttccaagtta gcgaagacga ggttactccg 1440
aacatgcgcc gtcaggccaa agctgtcaac tttggcatcg tctacggtat ttccgactac 1500
ggcctggcac agaacctgaa tatctctcgc aaagaagccg cggaattcat cgaacgttat 1560
ttcgaatcct tcccgggtgt aaaacgttac atggagaaca tcgtccagga agctaagcag 1620
aaaggctatg taactactct gctgcatcgt cgccgttacc tgcctgatat taactctcgt 1680
aacttcaacg tgcgttcttt cgctgaacgc atggcgatga acactccaat ccaaggttct 1740
gcggcggaca tcattaaaaa ggcaatgatt gatctgaatg cccgtctgaa agaagagcgt 1800
ctgcaggctc acctgctgct gcaggtgcac gaggagctga ttctggaagg accgaaagaa 1860
gaaatggaac gcctgtgtcg tctggtgccg gaggttatgg aacaggcggt tacgctgcgc 1920
gtaccgctga aagtagacta ccactacggt tctacttggt acgacgccaa a 1971
<210> 47
<211> 2061
<212> DNA
<213> Artificial Sequence
<400> 47
atgcaccacc accaccatca tccacgtggt gttgatccgt cccgtaaaga aaaccatctg 60
agcgacgaag atttcaaagc ggttttcggt atgacccgtt ctgctttcgc ccgtctgcca 120
ctgtggggtt ctggttccaa aatggcgttt accctggctg accgcgtgac cgaggagatg 180
ctggcagaca aagcagctct ggtggtggaa gttgttgaag aaaactacca tgacgcacca 240
atcgttggca tcgcagttgt taacgaacat ggccgtttct ttctgcgtcc ggaaactgcg 300
ctggcagatc cgcaattcgt cgcttggctg ggtgacgaaa ctaaaaaaaa aagcatgttc 360
gattccaaac gtgccgcggt agctctgaaa tggaaaggca tcgaactgtg cggcgttagc 420
ttcgacctgc tgctggctgc ttatctgctg gatcctgcgc agggcgttga cgacgtagca 480
gcagctgcaa aaatgaagca gtacgaagca gttcgtccag acgaagccgt ttacggcaaa 540
ggtgcaaaac gtgcggttcc agacgaaccg gttctggcgg aacacctggt tcgcaaagcc 600
gctgctatct gggaactgga acgcccgttc ctggatgaac tgcgtcgtaa cgaacaagat 660
cgtctgctgg tcgaactgga acagccgctg tctagcattc tggctgaaat ggaatttgcg 720
ggcgttaaag tagacactaa acgtctggaa cagatgggca aagaactggc agaacagctg 780
ggtactgttg aacagcgtat ctacgaactg gcgggccagg aattcaacat caactctccg 840
aagcagctgg gcgttattct gttcgaaaaa ctgcaactgc cggtgctgaa aaaaactaaa 900
accggttact ccaccagcgc tgacgtactg gagaagctgg ccccatacca tgaaattgtt 960
gaaaacattc tgcactatcg tcagctgggc aaactgcagt ctacttatat cgatccgctg 1020
ccggacctga tccacccgcg taccctgcgt ctgcatacca tcttcaacca ggcgctgacc 1080
cagaccggtc gtctgtcttc taccgagccg aacctgcaga acatcccgat ccgtctggaa 1140
gaaggtcgta aaatccgtca ggctttcgtt ccgagcgaat ctgactggct gatcttcgct 1200
gcggattacg accagattga actgcgtgtg ctggctcaca tcgctgagga tgacaatctg 1260
atggaagctt tccgccgtga tctggacatc cacaccaaaa ctgcgatgga tatcttccaa 1320
gttagcgaag acgaggttac tccgaacatg cgccgtcagg ccaaagctgt caactttggc 1380
atcgtctacg gtatttccga ctacggcctg gcacagaacc tgaatatctc tcgcaaagaa 1440
gccgcggaat tcatcgaacg ttatttcgaa tccttcccgg gtgtaaaacg ttacatggag 1500
aacatcgtcc aggaagctaa gcagaaaggc tatgtaacta ctctgctgca tcgtcgccgt 1560
tacctgcctg atattaactc tcgtaacttc aacgtgcgtt ctttcgctga acgcatggcg 1620
atgaacactc caatccaagg ttctgcggcg gacatcatta aaaaggcaat gattgatctg 1680
aatgcccgtc tgaaagaaga gcgtctgcag gctcacctgc tgctgcaggt gcacgaggag 1740
ctgattctgg aaggaccgaa agaagaaatg gaacgcctgt gtcgtctggt gccggaggtt 1800
atggaacagg cggttacgct gcgcgtaccg ctgaaagtag actaccacta cggttctact 1860
tggtacgacg ccaaaggcag cggctctacc gtgaaattca aatacaaagg cgaagagaag 1920
gaggttgaca tctctaaaat caaaaaagtc tggcgtgttg gtaaaatgat ctccttcacc 1980
tacgacgaca acggtaaaac cggccgtggt gctgtctctg aaaaggatgc accgaaagaa 2040
ctgctgcaga tgctggaaaa a 2061
<210> 48
<211> 2097
<212> DNA
<213> Artificial Sequence
<400> 48
atgcaccacc accaccatca tccacgtggt gttgatccgt cccgtaaaga aaaccatctg 60
agcgacgaag atttcaaagc ggttttcggt atgacccgtt ctgctttcgc ccgtctgcca 120
ctgtggaaac agcagaaact gaaaaagaaa aaaggcctgt tcggttctgg ttccaaaatg 180
gcgtttaccc tggctgaccg cgtgaccgag gagatgctgg cagacaaagc agctctggtg 240
gtggaagttg ttgaagaaaa ctaccatgac gcaccaatcg ttggcatcgc agttgttaac 300
gaacatggcc gtttctttct gcgtccggaa actgcgctgg cagatccgca attcgtcgct 360
tggctgggtg acgaaactaa aaaaaaaagc atgttcgatt ccaaacgtgc cgcggtagct 420
ctgaaatgga aaggcatcga actgtgcggc gttagcttcg acctgctgct ggctgcttat 480
ctgctggatc ctgcgcaggg cgttgacgac gtagcagcag ctgcaaaaat gaagcagtac 540
gaagcagttc gtccagacga agccgtttac ggcaaaggtg caaaacgtgc ggttccagac 600
gaaccggttc tggcggaaca cctggttcgc aaagccgctg ctatctggga actggaacgc 660
ccgttcctgg atgaactgcg tcgtaacgaa caagatcgtc tgctggtcga actggaacag 720
ccgctgtcta gcattctggc tgaaatggaa tttgcgggcg ttaaagtaga cactaaacgt 780
ctggaacaga tgggcaaaga actggcagaa cagctgggta ctgttgaaca gcgtatctac 840
gaactggcgg gccaggaatt caacatcaac tctccgaagc agctgggcgt tattctgttc 900
gaaaaactgc aactgccggt gctgaaaaaa actaaaaccg gttactccac cagcgctgac 960
gtactggaga agctggcccc ataccatgaa attgttgaaa acattctgca ctatcgtcag 1020
ctgggcaaac tgcagtctac ttatatcgat ccgctgccgg acctgatcca cccgcgtacc 1080
ctgcgtctgc ataccatctt caaccaggcg ctgacccaga ccggtcgtct gtcttctacc 1140
gagccgaacc tgcagaacat cccgatccgt ctggaagaag gtcgtaaaat ccgtcaggct 1200
ttcgttccga gcgaatctga ctggctgatc ttcgctgcgg attacgacca gattgaactg 1260
cgtgtgctgg ctcacatcgc tgaggatgac aatctgatgg aagctttccg ccgtgatctg 1320
gacatccaca ccaaaactgc gatggatatc ttccaagtta gcgaagacga ggttactccg 1380
aacatgcgcc gtcaggccaa agctgtcaac tttggcatcg tctacggtat ttccgactac 1440
ggcctggcac agaacctgaa tatctctcgc aaagaagccg cggaattcat cgaacgttat 1500
ttcgaatcct tcccgggtgt aaaacgttac atggagaaca tcgtccagga agctaagcag 1560
aaaggctatg taactactct gctgcatcgt cgccgttacc tgcctgatat taactctcgt 1620
aacttcaacg tgcgttcttt cgctgaacgc atggcgatga acactccaat ccaaggttct 1680
gcggcggaca tcattaaaaa ggcaatgatt gatctgaatg cccgtctgaa agaagagcgt 1740
ctgcaggctc acctgctgct gcaggtgcac gaggagctga ttctggaagg accgaaagaa 1800
gaaatggaac gcctgtgtcg tctggtgccg gaggttatgg aacaggcggt tacgctgcgc 1860
gtaccgctga aagtagacta ccactacggt tctacttggt acgacgccaa aggcagcggc 1920
tctaccgtga aattcaaata caaaggcgaa gagaaggagg ttgacatctc taaaatcaaa 1980
aaagtctggc gtgttggtaa aatgatctcc ttcacctacg acgacaacgg taaaaccggc 2040
cgtggtgctg tctctgaaaa ggatgcaccg aaagaactgc tgcagatgct ggaaaaa 2097
<210> 49
<211> 2784
<212> DNA
<213> Artificial Sequence
<400> 49
atgagcaaat ccaacgaacc aggcaaagcc accggcgaag gcaaaccggt caacaacaaa 60
tggctgaaca acgcgggtaa ggacctgggt agcccggtcc cggaccgtat cgctaacaag 120
ctgcgcgaca aagaatttga atccttcgat gacttccgcg aaactttctg ggaagaagtg 180
tctaaagatc cggagctgtc caaacagttc tctcgcaaca acaacgaccg catgaaagta 240
ggtaaagctc ctaaaacccg cacgcaggat gtttccggca aacgtacctc cttcgaactg 300
aatcatcaga aaccgatcga acagaacggt ggcgtttacg atatggataa catttccgta 360
gttaccccga aacgtaacat cgacatcgaa ggcggttctg gttcctccga tagcgaagtg 420
aaccaggaag ctaaaccgga agtgaagccg gaagtgaaac cagaaaccca catcaacctg 480
aaagttagcg atggctcctc tgagatcttc tttaaaatca aaaaaaccac cccgctgcgt 540
cgcctgatgg aagcgttcgc aaaacgccag ggtaaagaaa tggactccct gcgtttcctg 600
tacgatggta tccgtattca agctgatcag acgccggaag atctggatat ggaggataat 660
gacattatcg aagcccatcg tgaacagatc ggcggtggtt ctggttctcc acgtggtgtt 720
gatccgtccc gtaaagaaaa ccatctgagc gacgaagatt tcaaagcggt tttcggtatg 780
acccgttctg ctttcgcccg tctgccactg tggaaacagc agaaactgaa aaagaaaaaa 840
ggcctgttcg gttctggttc caaaatggcg tttaccctgg ctgaccgcgt gaccgaggag 900
atgctggcag acaaagcagc tctggtggtg gaagttgttg aagaaaacta ccatgacgca 960
ccaatcgttg gcatcgcagt tgttaacgaa catggccgtt tctttctgcg tccggaaact 1020
gcgctggcag atccgcaatt cgtcgcttgg ctgggtgacg aaactaaaaa aaaaagcatg 1080
ttcgattcca aacgtgccgc ggtagctctg aaatggaaag gcatcgaact gtgcggcgtt 1140
agcttcgacc tgctgctggc tgcttatctg ctggatcctg cgcagggcgt tgacgacgta 1200
gcagcagctg caaaaatgaa gcagtacgaa gcagttcgtc cagacgaagc cgtttacggc 1260
aaaggtgcaa aacgtgcggt tccagacgaa ccggttctgg cggaacacct ggttcgcaaa 1320
gccgctgcta tctgggaact ggaacgcccg ttcctggatg aactgcgtcg taacgaacaa 1380
gatcgtctgc tggtcgaact ggaacagccg ctgtctagca ttctggctga aatggaattt 1440
gcgggcgtta aagtagacac taaacgtctg gaacagatgg gcaaagaact ggcagaacag 1500
ctgggtactg ttgaacagcg tatctacgaa ctggcgggcc aggaattcaa catcaactct 1560
ccgaagcagc tgggcgttat tctgttcgaa aaactgcaac tgccggtgct gaaaaaaact 1620
aaaaccggtt actccaccag cgctgacgta ctggagaagc tggccccata ccatgaaatt 1680
gttgaaaaca ttctgcacta tcgtcagctg ggcaaactgc agtctactta tatcgatccg 1740
ctgccggacc tgatccaccc gcgtaccctg cgtctgcata ccatcttcaa ccaggcgctg 1800
acccagaccg gtcgtctgtc ttctaccgag ccgaacctgc agaacatccc gatccgtctg 1860
gaagaaggtc gtaaaatccg tcaggctttc gttccgagcg aatctgactg gctgatcttc 1920
gctgcggatt acgaccagat tgaactgcgt gtgctggctc acatcgctga ggatgacaat 1980
ctgatggaag ctttccgccg tgatctggac atccacacca aaactgcgat ggatatcttc 2040
caagttagcg aagacgaggt tactccgaac atgcgccgtc aggccaaagc tgtcaacttt 2100
ggcatcgtct acggtatttc cgactacggc ctggcacaga acctgaatat ctctcgcaaa 2160
gaagccgcgg aattcatcga acgttatttc gaatccttcc cgggtgtaaa acgttacatg 2220
gagaacatcg tccaggaagc taagcagaaa ggctatgtaa ctactctgct gcatcgtcgc 2280
cgttacctgc ctgatattaa ctctcgtaac ttcaacgtgc gttctttcgc tgaacgcatg 2340
gcgatgaaca ctccaatcca aggttctgcg gcggacatca ttaaaaaggc aatgattgat 2400
ctgaatgccc gtctgaaaga agagcgtctg caggctcacc tgctgctgca ggtgcacgag 2460
gagctgattc tggaaggacc gaaagaagaa atggaacgcc tgtgtcgtct ggtgccggag 2520
gttatggaac aggcggttac gctgcgcgta ccgctgaaag tagactacca ctacggttct 2580
acttggtacg acgccaaagg cagcggctct accgtgaaat tcaaatacaa aggcgaagag 2640
aaggaggttg acatctctaa aatcaaaaaa gtctggcgtg ttggtaaaat gatctccttc 2700
acctacgacg acaacggtaa aaccggccgt ggtgctgtct ctgaaaagga tgcaccgaaa 2760
gaactgctgc agatgctgga aaaa 2784
<210> 50
<211> 141
<212> DNA
<213> Artificial Sequence
<400> 50
ccacgtggtg ttgatccgtc ccgtaaagaa aaccatctga gcgacgaaga tttcaaagcg 60
gttttcggta tgacccgttc tgctttcgcc cgtctgccac tgtggaaaca gcagaaactg 120
aaaaagaaaa aaggcctgtt c 141

Claims (9)

1.一种Bst DNA聚合酶重组突变体，其特征在于其氨基酸序列如SEQ ID No.2、7-16中任一项所示。
2.权利要求1所述的Bst DNA聚合酶重组突变体的编码DNA，其特征在于：其核苷酸序列如SEQ ID No.35、40-49所示。
3.一种超快磁珠LAMP检测方法，其特征在于其步骤包括：
（1）提取样品中的核酸；
（2）磁珠富集样品中的核酸；
（3）将步骤（2）的磁珠重悬到LAMP反应液中进行扩增，其中LAMP反应液含有权利要求1所述的Bst DNA聚合酶重组突变体。
4.根据权利要求3所述的超快磁珠LAMP检测方法，其特征在于：所述LAMP反应液还含有2-20 mM二价金属离子。
5.根据权利要求4所述的超快磁珠LAMP检测方法，其特征在于：所述二价金属离子为镁离子、锰离子、镉离子、镍离子、锌离子、铜离子、钴离子、钙离子或亚铁离子中的一种或数种。
6.根据权利要求3-5中任一项所述的超快磁珠LAMP检测方法，其特征在于：所述LAMP反应液还含有5-50 mM Tris、20-200 mM 氯化铵、20-200 mM 氯化钾、1-4 M甜菜碱、0.1-1 mMdNTP。
7.根据权利要求6所述的超快磁珠LAMP检测方法，其特征在于：步骤（1）中采用核酸提取试剂盒进行样品中核酸的提取。
8.根据权利要求6所述的超快磁珠LAMP检测方法，其特征在于：步骤（2）中的磁珠为RNA结合磁珠。
9.根据权利要求8所述的超快磁珠LAMP检测方法，其特征在于：步骤（2）中还需要加入磁珠结合缓冲液，所述磁珠结合缓冲液的组分包括4%-40%的聚乙二醇8000、0.2-2 M氯化钠、10-100 mM 三羟甲基氨基甲烷、0.2%-2% Triton X-100和0.2%-2% 吐温20中的一种或多种。
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