阅读说明：本技术 用于碱基编辑的融合蛋白 (Fusion proteins for base editing ) 是由 陈佳 杨力 黄行许 杨贝 王潇 李佳楠 于 2019-02-22 设计创作，主要内容包括：本发明提供一种融合蛋白,所述融合蛋白包括载脂蛋白BmRNA编辑酶催化亚基3A(APOBEC3A)和成簇规律间隔的短回文重复序列(CRISPR)相关(Cas)蛋白,任选地其进一步与尿嘧啶糖基化酶抑制剂(UGI)融合。即使胞嘧啶在GpC中或为甲基化的,这种融合蛋白也能够通过使胞嘧啶脱氨基为尿嘧啶,从而在DNA中进行碱基编辑。(The present invention provides a fusion protein comprising an apolipoprotein b mrna editing enzyme catalytic subunit 3A (APOBEC3A) and a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) -associated (Cas) protein, optionally further fused to a Uracil Glycosylase Inhibitor (UGI). Even if cytosine is in the GpC or methylated, such fusion proteins are able to base edit in DNA by deaminating cytosine to uracil.)

用于碱基编辑的融合蛋白

本申请要求2018年2月23日提交的PCT/CN2018/076991和2018年8月14日提交的PCT/CN2018/100411的优先权。上述申请的说明书通过引用整体合并于此。

技术领域

本发明属于基因编辑领域，具体涉及一种用于碱基编辑的融合蛋白。

背景技术

基因组编辑是一种基因工程，其使用工程核酸酶(分子剪刀)在生物体的基因组中***、删除或取代DNA。使用基因组编辑工具对细胞和生物体的基因组进行遗传操作，在生命科学研究、生物技术、农业技术开发和最重要的药物或临床创新方面具有广泛的应用兴趣。例如，基因组编辑可用于纠正遗传疾病背后的驱动突变，从而完全治愈生物体内的这些疾病；基因组编辑也可用于改造作物的基因组，从而提高作物产量并赋予作物对环境污染或病原体感染的抗性；同样地，通过精确的基因组编辑进行微生物基因组转化对于可再生生物能源的开发具有重要意义。

CRISPR/Cas(成簇规律间隔的短回文重复序列/CRISPR相关蛋白)系统因其无与伦比的编辑效率、便利性和在生物体中的潜在应用而成为最强大的基因组编辑工具。在向导RNA(gRNA)的指导下，Cas核酸酶可以在各种细胞(细胞系和生物体细胞)的靶基因组位点引起DNA双链断裂(DSB)。之后这些DSB被内源性DNA修复系统修复，该修复系统可用于所需的基因组编辑。

通常来说，DSB可以激活两种主要的DNA修复途径，非同源末端链(NHEJ)和同源介导修复(HDR)。NHEJ能在DSB周围的基因组DNA区域诱导随机***或缺失，从而导致开放阅读框(ORF)移位，并最终致使基因失活。相反，当触发HDR时，外源供体的DNA模板序列通过同源重组机制取代靶位点的基因组DNA序列，从而导致基因突变的校正。

然而，HDR介导的基因校正的实际效率很低(通常<5％)，因为同源重组的发生既是细胞类特异性的又是细胞周期依赖性的，并且NHEJ的触发频率高于HDR。因此，HDR相对低的效率限制了CRISPR/Cas基因组编辑工具在精确基因治疗(疾病驱动的基因校正)领域中的转化。

最近发明的将CRISPR/Cas和APOBEC(催化多肽样载脂蛋白B mRNA编辑酶)胞嘧啶脱氨酶家族整合为一体的碱基编辑器(BE)，极大地提高了CRISPR/Cas9介导的基因校正的效率。大鼠APOBEC1(rA1)的胞嘧啶(C)脱氨基活性物与Cas9缺刻酶(nCas9)融合后，可以有目的地导向基因组中的靶碱基，并催化这些碱基上的C被T取代。

然而，目前基于rA1的BE不能有效地编辑伴随G的C(即GpC的C)，从而限制了基因组的靶向宽度。因此，非常需要创建出能够有效编辑GpC中的C的新BE。这样的新BE将确保我们在各种生物体更广泛的基因组中进行有效的碱基编辑。重要的是，这类对GpC中的C有高效作用的BE将促进临床转化，尤其在涉及到修复疾病相关的GpT突变为GpC突变体的基因治疗时。

发明简述

本公开表明，当载脂蛋白B mRNA编辑酶催化亚基3A(APOBEC3A或A3A)与成簇规律间隔短回文重复序列(CRISPR)相关(Cas)蛋白融合时，任选地进一步融合尿嘧啶糖基化酶抑制剂(UGI)，得到的融合蛋白能够有效地将胞嘧啶脱氨基成尿嘧啶，导致C被T取代。令人惊讶和出乎意料的是，即使在C伴随G(即，在GpC二核苷酸环境中)或C被甲基化时，这种碱基编辑也是有效的。在A3A含有一些测试的突变时，这种编辑效率能进一步提高。由于胞嘧啶甲基化在活细胞中很常见，因此这种编辑具有重要的临床意义。

在常规碱基编辑器中，Cas9是常用的DNA核酸内切酶。在碱基编辑器中，当Cas12a(Cpf1)与APOBEC1一起使用时，Cas12a(Cpf1)具备识别富含A/T的序列的优势。另一个惊讶的发现是，当A3A取代APOBEC1时，编辑效率大大提高。然而，A3A含有一些测试的突变时，Cas12a-A3A的编辑效率能进一步提高。

因此，在一个实施方案中，本公开提供了包含第一片段和第二片段的融合片段，第一片段包含载脂蛋白B mRNA编辑酶催化亚基3A(APOBEC3A)，第二片段包含成簇规律间隔短回文重复序列(CRISPR)相关(Cas)蛋白。在一些实施方案中，所述融合蛋白还包含尿嘧啶糖基化酶抑制剂(UGI)。

优选地，融合蛋白共包含少于3000、2500、2200、2100、2000、1900、1800、1700、1600或1500个氨基酸残基。

在一些实施方案中，根据序列SEQ ID NO:1中的残基编号，APOBEC3A是野生型人类APOBEC3A或具有选自Y130F、D131Y、D131E、Y132D、W104A、、W98Y、P134Y及其组合组成的组的突变型人类APOBEC3A的突变体，所述突变体保留胞苷脱氨酶活性。

在一些实施方案中，根据SEQ ID NO:1中的残基编号，所述APOBEC3A是人类APOBEC3A突变体，其含有选自Y130F+D131E+Y132D、Y130F+D131Y+Y132D、W98Y+W104A、W98Y+P134Y、W104A+P134Y、W104A+Y130F、W104A+Y132D、W98Y+W104A+Y130F、W98Y+W104A+Y132D、W104A+Y130F+P134Y和W104A+Y132D+P134Y的突变。

在一些实施方案中，APOBEC3A包含如SEQ ID NO:1所示的氨基酸序列或与如SEQID NO:1的氨基酸残基的第29-199位具有至少90％的序列同一性并保留胞苷脱氨酶活性。在一些实施方案中，APOBEC3A含有选自如SEQ ID NO:1-10和22-36组成的组所示的氨基酸序列。

在一些实施方案中，Cas蛋白选自SpCas9、FnCas9、St1Cas9、St3Cas9、NmCas9、SaCas9、AsCpf1、LbCpf1、FnCpf1、VQR SpCas9、EQR SpCas9、VRER SpCas9、RHA FnCas9、KKHSaCas9、NmeCas9、StCas9、CjCas9、AsCpf1、FnCpf1、SsCpf1、PcCpf1、BpCpf1、CmtCpf1、LiCpf1、PmCpf1、Pb3310Cpf1、Pb4417Cpf1、BsCpf1、EeCpf1、BhCas12b、AkCas12b、EbCas12b、LsCas12b、RfCas13d、LwaCas13a、PspCas13b、PguCas13b、RanCas13b、CasX和CasY组成的组。在一些实施方案中，Cas蛋白是选自SpCas9、FnCas9、St1Cas9、St3Cas9、NmCas9、SaCas9、AsCpf1、LbCpf1、FnCpf1、VQRSpCas9、EQR SpCas9、VRER SpCas9、RHA Cas9、KKH SaCas9、NmeCas9、StCas9、CjCas9、AsCpf1、FnCpf1、SsCpf1、PcCpf1、BpCpf1、CmtCpf1、LiCpf1、PmCpf1、Pb3310Cpf1、Pb4417Cpf1、BsCpf1、EeCpf1、BhCas12b、AkCas12b、EbCas12b、LsCas12b、RfCas13d、LwaCas13a、PspCas13b、PguCas13b、RanCas13b、CasX和CasY中组成的组的蛋白的突变体，其中所述突变体保留DNA结合能力但不引入双链DNA断裂。在一些实施方案中，突变体能将缺刻引入到由所述突变体结合的双链DNA的一条链上。在一些实施方案中，Cas蛋白包含如SEQ ID NO:11和37-39所示的氨基酸序列的中任一个。

在一些实施方案中，UGI含有如SEQ ID NO:12所示的氨基酸序列或与SEQ ID NO:12具有至少90％的序列同一性并保留尿嘧啶糖基化酶抑制活性。

在一些实施方案中，第一片段位于第二片段的N末端。在一些实施方案中，第一片段位于第二片段的N末端，第二片段位于UGI的N末端。

在一些实施方案中，融合蛋白还包含第一片段和第二片段之间的肽接头。在一些实施方案中，肽接头具有1至100个氨基酸残基。在一些实施方案中，肽接头的至少10％、20％、30％、40％、50％、60％、70％、80％或90％的氨基酸残基为选自由以下的氨基酸残基组成的组：丙氨酸、甘氨酸、半胱氨酸和丝氨酸。在一些实施方案中，肽接头具有如SEQ IDNO:13或14所示的氨基酸序列。在一些实施方案中，融合蛋白还包含核定位序列。

融合蛋白的非限制性示例包括具有选自由如SEQ ID NO:16-20和40-50组成的组所示的氨基酸序列。

在另一个实施方案中，提供了一种融合蛋白，其包含第一片段和第二片段，第一片段包含载脂蛋白B mRNA编辑酶催化亚基3A(APOBEC3A)，第二片段包含普雷沃氏菌属(Prevotella)和弗朗西斯氏菌属(Francisella 1，Cpf1)中的CRISPR相关内切核酸酶。在一些实施方案中，Cpf1是无催化活性的。

在一些实施方案中，Cpf1(Cas12a)可选自AsCpf1、LbCpf1和FnCpf1。在具体的实施方案中，Cpf1是无催化活性的毛螺菌科Cpf1(dLbCpf1)。

在一些实施方案中，根据SEQ ID NO:1的残基编号，APOBEC3A是野生型人APOBEC3A或具有选自由Y130F、D131Y、D131E、Y132D、W104A、W98Y、P134Y及其组合组成的组的突变的人类APOBEC3A突变体，其中所述突变体保留胞苷脱氨酶活性。

还提供了编码本公开中融合蛋白的多核苷酸。而且，在另一个实施方案中，提供了包含本公开的融合蛋白和药学上可接受载体的组合物。在一些实施方案中，所述组合物进一步包含向导RNA。

一些实施方案还提供了使用融合蛋白和组合物的方法。在一个实施方案中，提供了用于编辑靶多核苷酸的方法，其包括将本公开的融合蛋白和与靶多核苷酸具有至少部分序列互补性的向导RNA接触至所述靶多核苷酸，其中所述编辑包括靶多核苷酸中胞嘧啶(C)的脱氨基。在一些实施方案中，C在GpC中。在一些实施方案中，C为甲基化的。在一些实施方案中，所述接触在体外、离体或体内发生。在一些实施方案中，所述方法进一步包括使所述靶多核苷酸和未与Cas蛋白融合的尿嘧啶糖基化酶抑制剂(UGI)接触。

具体实施方式

实施例1：碱基编辑器

人类载脂蛋白BmRNA编辑酶催化亚基3A(APOBEC3A，hA3A；SEQ ID NO:1)包含在表达载体中，所述载体还包含Cas9缺刻酶(SEQ ID NO:11)和尿嘧啶DNA糖基化酶抑制剂[芽孢杆菌噬菌体AR9](SEQ ID NO:12)。Cas9缺刻酶含有一种Asp10Ala突变，所述Asp10Ala突变使自身的双链核酸酶失活的同时允许其在其中一条链上引入缺刻。

将融合载体、hA3A-nCas9-UGI(hA3ABE，SEQ ID NO:21)和sgRNA表达载体共转染到真核细胞中(图1A)，以进行基因组中sgRNA靶位点的C至T碱基编辑。PCR扩增目标基因组的DNA后，通过SangerDNA测序确定基因组目标位点的C至T碱基编辑效率。如两个sgRNA靶位点(sgFANCF-M-L6和sgSITE4)所示，与共表达BE3(APOBEC1-nCas9-UGI)和sgRNA(图1B，虚线框)相比，共表达hA3ABE和sgRNA能在GpC的C上执行有效的C至T碱基编辑。

接下来，将突变Y130F(SEQ ID NO:2)和Y132D(SEQ ID NO:3)分别引入构建体中的hA3A基因，由此产生碱基编辑器hA3A-BE-Y130F或hA3A-BE-Y132D(图2A)。hA3A-BE中的Y130F和Y132D突变缩小了碱基编辑的窗口，进一步提高了hA3A-BE的编辑精度(图2B)。

此外，将突变W104A(SEQ ID NO:4)和D131Y(SEQ ID NO:5)分别引入hA3A-BE的hA3A基因中，由此产生碱基编辑器hA3A-BE-W104A或hA3A-BE-D131Y(图3A)。与hA3A-BE相比，hA3A-BE-W104A和hA3A-BE-D131Y都提高了所需的C被T碱基取代的效率(图3B)，实现了更高的碱基编辑效率。

在进一步的实验中，测试了hA3A-BE3(图4A)中人类APOBEC3A(hA3A)的三个氨基酸变化(Y130F-D131E-Y132D，SEQ ID NO：22或Y130F-D131Y-Y132D，SEQ ID NO：23)并且发现这两个碱基编辑器(hA3A-BE-Y130F-D131E-Y132D和hA3A-BE-Y130F-D131Y-Y132D)具有更窄的编辑窗口(目标区域中的4-6位点)，因此具有更高的编辑精度(图4B)。

实施例2：使用人APOBEC3A-Cas9融合蛋白在甲基化区域进行有效的碱基编辑

碱基编辑器(BE)能够产生靶向的单核苷酸突变，但目前使用的基于大鼠APOBEC1的BE在编辑高度甲基化区域或GpC环境中的胞嘧啶时效率相对较低。通过筛选各种APOBEC/AID脱氨酶，该实施例表明人类的APOBEC3A缀合的BE和设计为具有较窄编辑窗口的版本可以在具有高甲基化水平和GpC二核苷酸含量的环境中介导有效的C至T碱基编辑。

将胞苷脱氨酶与Cas9或Cpf1结合的碱基编辑器(BE)已成功应用于靶向碱基编辑，包括C至T。据报道，许多人类疾病是由基因组DNA的点突变驱动的。利用最近开发的BE，可以潜在地纠正这些与疾病相关的点突变，从而提供新的治疗选择。通过分析疾病相关的T至C突变，其在理论上能使用BE还原为胸腺嘧啶，该实例发现在CpG二核苷酸环境中约43％的该突变位于胞嘧啶上(图5a)。众所周知，CpG的C通常在哺乳动物细胞中被甲基化，并且C的甲基化强烈抑制一些由APOBEC/AID脱氨酶催化的胞苷脱氨基。该实施例显示CpG二核苷酸甲基化阻碍了当前BE的C至T碱基编辑，并且该实施例已经成功开发了用于在高度甲基化区域中有效C至T碱基编辑的BE。

方法和材料

质粒构建

使用引物组(hA3A_PCR_F/hA3A_PCR_R)，并以pUC57-Human_APOBEC3A作为模板(由Genscript合成)，扩增片段Human_APOBEC3A。然后使用质粒重组试剂盒(Vazyme，C112-02)将Human_APOBEC3A片段克隆到经SacI和SmaI线性化的pCMV-BE3(addgene，73021)中以生成hA3A-BE3表达载体pCMV-hAPOBEC3A-XTEN-D10A-SGGS-UGI-SGGS-NLS。用相同的方法构建hA3B-BE3、hA3C-BE3、hA3D-BE3、hA3F-BE3、hA3G-BE3、hA3H-BE3、hAID-BE3、hA1-BE3、mA3-BE3、mAID-BE3、mA1-BE3、cAICDA-BE3这些表达载体。pmCDA1表达载体pcDNA 3.1_pCMV-nCas-PmCDA1-ugipH1-gRNA(HPRT)购自Addgene(79620)。

使用引物组(SupF_PCR_F/SupF_PCR_R)，并以穿梭载体pSP189作为模板，扩增片段SupF。然后将片段SupF克隆到pEASY-ZERO-BLUNT(TransGen Biotech，CB501)中，以产生载体pEASY-SupF-ZERO-BLUNT。

将寡核苷酸SupF_sg1_FOR/SupF_sg1_REV和SupF_sg2_FOR/SupF_sg2_REV退火，并连接到经BsaI线性化的pGL3-U6-sgRNA-PGK-嘌呤霉素(addgene，51133)中，以产生靶向pEASY-SupF-ZERO-BLUNT中SupF基因的sgRNA表达载体psgSupF-1和psgSupF-2。

使用两个引物组(hA3A_PCR_F/hA3A_Y130F_PCR_R)(hA3A_Y130F_PCR_F/hA3A_PCR_R)扩增含Y130F的片段hA3A-Y130F。然后将该片段克隆到经ApaI和SmaI线性化的hA3A-BE3表达载体中，以产生hA3A-BE3-Y130F表达载体pCMV-hAPOBEC3A_Y130F-XTEN-D10A-SGGS-UGI-SGGS-NLS。以相同方法构建hA3A-BE3-D131Y、hA3A-BE3-Y132D、hA3A-BE3-C101S和hA3A-BE3-C106S表达载体。

引物组(hA3A_PCR_F/hA3A_PCR_R)用于扩增片段Human_APOBEC3A_Y130F，并使用hA3A-BE3-Y130F作为模板。然后将片段Human_APOBEC3A_Y130F克隆到经SacI和SmaI线性化的pCMV-eBE-S3¹⁹中以生成hA3A-eBE-Y130F表达载体pCMV-hAPOBEC3A_Y130F-XTEN-D10A-SGGS-UGI-SGGS-NLS-T2A-UGI-NLS-UGI-NLS-T2A-UGI-NLS。通过类似的方法构建了hA3A-eBE-Y132D表达载体。

将寡核苷酸hEMX1_FOR/hEMX1_REV退火并连接到经BsaI线性化的pGL3-U6-sgRNA-PGK-嘌呤霉素中，以产生sgEMX1表达载体psgEMX1。用相同方法构建其他sgRNA表达载体。

抗体

抗体购自以下渠道：抗α-微管蛋白(T6199)-Sigma；抗Cas9(ab204448)-Abcam。

免疫印迹分析

将蛋白样品在95℃下孵育20分钟，在样品上样缓冲液中通过SDS-PAGE分离，并将蛋白转移到硝酸纤维素膜上(Thermo Fisher Scientific)。用含有5％(w/v)脱脂奶粉的TBST(25mM Tris pH8.0、150mM NaCl和0.1％Tween 20)封闭2小时后，将膜与指定的一抗反应过夜。充分洗涤后，将膜与结合HRP的二抗反应1小时。反应条带在ECL(Thermo FisherScientific)显色，并用Amersham Imager 600进行检测。

细胞培养和转染

将来自ATCC的HEK293T细胞保存在DMEM(10566，Gibco/Thermo FisherScientific)+10％FBS(16000-044，Gibco/Thermo Fisher Scientific)中，并定期测试以排除支原体污染。

dCas9-Suntag-TetCD系统用于诱导含有天然高水平甲基化的基因组区域(如FANCF、MAGEA1和MSSK1区域)的靶向去甲基化。dCas9-DNMT3a-DNMT31系统用于诱导含有天然低水平甲基化的基因组区域(如VEGFA和PDL1区域)的靶向甲基化。使用LIPOFECTAMINE2000(Life，Invitrogen)与3μg pCAG-scFvGCN4sfGFPTET1CD(由Genscript合成)和1μg sgRNA表达载体或3μg dCas9-DNMT3a-DNMT3l(由Genscript合成的载体)转染HEK293T细胞。转染24小时后，加入杀稻瘟菌素(10μg/ml，Sigma，15205)和嘌呤霉素(1μg/ml，Merck，540411)。一周后，收集一部分细胞确定DNA甲基化水平，其他细胞则保存在液氮中用于碱基编辑。诱导基因组DNA甲基化/去甲基化的sgRNA同样用于诱导碱基编辑。

为了基因组DNA中的碱基编辑，将HEK293T细胞以每孔1.6×10⁵的密度接种于24孔板中，并用200μl不含血清的Opti-MEM转染，所述Opti-MEM含有5.04μl LIPOFECTAMINELTX(Life，Invitrogen)，1.68μl LIPOFECTAMINE plus(Life，Invitrogen)，1μg BE3表达载体(或hA3A-BE3、hA3A-BE3-Y130F、hA3A-BE3-D131Y、hA3A-BE3-Y132D、hA3A-BE3-C101S、hA3A-BE3-C106S、hA3A-eBE-Y130F、hA3A-eBE-Y132D表达载体)和0.68μg sgRNA表达载体。72小时后，用Quick Extract^TM DNA提取液(QE09050，Epicentre)提取细胞中的基因组DNA，或在2×SDS上样缓冲液中裂解细胞用于进行蛋白质印迹分析。

为了在质粒载体中进行碱基编辑，将293T细胞以每孔3×10⁵的密度接种于6孔板中，并用500μl无血清Opti-MEM转染，所述无血清Opti-MEM包含4μl LIPOFECTAMINELTX(Life，Invitrogen)，2μl LIPOFECTAMINEplus(Life，Invitrogen)，1μg BE3表达载体(或hA3A-BE3、hA3B-BE3、hA3C-BE3、hA3D-BE3、hA3F-BE3、hA3G-BE3、hA3H-BE3、hAID-BE3、hA1-BE3、mA3-BE3、mAID-BE3、mA1-BE3、cAICDA-BE3或pmCDA1表达载体)和0.5μg sgRNA表达载体。24小时后，将这些细胞用500μl不含血清的Opti-MEM转染，其中包含4μlLIPOFECTAMINELTX，2μl LIPOFECTAMINEplus和1.5μg未甲基化(或甲基化)的pEASY-SupF-ZERO-BLUNT。48小时后，用TIANprep Mini质粒试剂盒(DP103-A，TIANGEN)从细胞中提取质粒，或将细胞在2×SDS上样缓冲液中裂解以进行蛋白质印迹。

亚硫酸氢盐测序分析

根据EZDNA EZ DNA methylation-direct Kit(ZymoResearch，D5021)的说明，分离基因组DNA并用亚硫酸氢盐处理。使用Taq^TM Hot Start Version(Takara，R007B)对亚硫酸氢盐处理的DNA进行PCR扩增。将PCR产物连接到T-载体pMDTM19(Takara，3271)中。挑选出八个克隆并通过Sanger测序法(Genewiz)进行测序。补充表2列出了用于亚硫酸氢盐PCR的引物。

质粒DNA甲基化

为了进行体外甲基化，在20μl反应中，利用1μl CpG甲基转移酶(M.SssI，Life，EM0821)使2μl质粒DNA甲基化。体外甲基化后，用BstUI(NEB，R0518S)限制性酶切pEASY-SupF-ZERO-BLUNT以确定甲基化水平。

蓝/白斑筛选

从转染的细胞中提取的质粒被转化到大肠杆菌MBM7070菌中(lacZuag_amber)，其在37℃、含有50μg/ml卡那霉素，1mMIPTG和0.03％Blu-gal(Life，Invitrogen)的LB平板上过夜生长，之后在室温条件下放置一天(以最大程度地改善显色)。通过将白色菌落的数量除以总菌落的数量来计算累计的碱基编辑频率。

DNA文库的制备和测序

靶基因组位点使用高保真DNA聚合酶Prime STARHS(Clonetech)和每个位于经检测的sgRNA靶位点侧翼的引物进行PCR扩增。补充表2中列出了用于扩增靶基因组序列的PCR引物。索引的DNA文库通过对TruSeqChIP样品制备试剂盒(Illumina)来制备，并进行一些小的修改。简而言之，PCR产物通过Covaris S220片段化，然后使用TruSeqChIP样品制备试剂盒(Illumina)进行扩增。使用Illumina NextSeq 500(2×150)或Hiseq X Ten(2×150)(中国上海CAS-MPG合作伙伴计算生物学组学核心研究所)将具有不同标签的PCR产物汇集在一起进行深度测序，原始读数的质量由FastQC(可从www.bioinformatics.babraham.ac.uk/projects/fastqc/获得)评估。对于成对末端测序，仅使用R1读数。修剪两端具有Phred质量得分低于28的衔接子序列和读取序列。然后使用BWA-MEM算法(BWAv0.7.9a)将修剪的读数映射到靶序列。在用samtools(v0.1.18)堆积后，进一步计算***缺失和碱基取代。

***缺失频率计算

从靶位点的上游8个核苷酸到PAM位点的下游19个核苷酸(50bp)的比对区域中估计***缺失。随后通过将包含至少一个***和/或缺失的核苷酸的读数除以相同区域的所有映射读数来计算***缺失频率。

碱基取代计算

在所测定的sgRNA靶位点的每个位点选择碱基取代，所述靶位点映射有至少1,000个独立的读数，并且仅在目标碱基编辑位点观察到明显的碱基取代。通过将碱基取代读数除以总读数来计算碱基取代频率。

BE可靶向遗传变异的计算

来自NCBIClinVar数据库的单核苷酸变体(SNVs)与来自NCBIdbSNP数据库的致病性人类等位基因序列重叠，以计算致病性T至C和A至G突变。在3089个病原性T至C或A至G突变中，2499个突变可由SpCas9-BE3、SaCas9-BE3、dLbCpf1-BE或xCas9-BE3与附近的PAM序列编辑。这2499种BE可靶向的SNV可根据它们的3个相邻基偏好进一步细分，即CpA、CpC、CpG和CpT(图5a)。

统计分析

在这项研究中P值是根据单尾学生t检验计算得出的。

数据可用性

该研究的深度测序数据被保存在NCBI基因表达综合库(登录号GSE114999)和美国国家学组数据百科全书(登录号OEP000030)。

结果

该实施例首先检查了具有增加或减少的甲基化水平的人类细胞中常用的BE，即基于大鼠APOBEC1(rA1)的BE3的基本编辑效率。当DNMT3在天然低甲基化水平的区域促进DNA甲基化时，BE3的编辑频率降低。此外，当天然高甲基化水平的区域中DNA甲基化被TET1降低时，BE3诱导的编辑频率也会相应增加。这些结果表明，基于标准rA1的BE3在编辑嵌入高度甲基化的基因组区域的胞嘧啶时效率较低。值得注意的是，CpG和侧翼非CpG位点的DNA甲基化抑制了C至T编辑(CpG位点：中位数减少约28％，P＝2×10^-8，和非CpG侧翼位点：中位数减少约51％，P＝7×10^-10)。APOBEC持续使单链DNA上的胞苷脱氨基。CpG甲基化可能会影响APOBEC的滑动，因此会削弱其在侧翼非CpG位点上的脱氨基结合。

为了筛选在高甲基化环境里的有效碱基编辑，通过将Cas9缺刻酶与十五种不同的APOBEC/AID脱氨酶融合获得了一系列BE(图5b)。之后该实施例在已用于探测突变的大肠杆菌衍生的载体系统(图5b)中测试所述BE。在未甲基化的载体中，所述BE显示出不同水平的碱基编辑效率。包含人类APOBEC3A(hA3A-BE3，平均编辑频率约39％)、人类APOBEC3B(hA3B-BE3，平均编辑频率约33％)或人类AID(hAID-BE3，平均编辑频率约28％)的BE介导的碱基编辑与BE3水平相当(平均编辑频率约31％)(图5c)。而在甲基化载体中，与由BE3(平均编辑频率约12％)或其他测试的BE诱导的相对较低的编辑效率(平均编辑频率约1％-20％)(图5c))相比，只有hA3A-BE3能诱导有效的碱基编辑(平均编辑频率约35％)。值得注意的是，hA3A-BE3、BE3和其他测试的BE的蛋白质产物相当(图5d)。

与在大肠杆菌衍生载体中观察的相似，在所有测试的基因组区域中，无论是具有天然高甲基化背景(中位数约为1.7倍，P＝2×10^-10，图5e、f)还是具有诱导的高甲基化背景(中位数约为1.8倍，P＝5×10^-4)，hA3A-BE3的碱基编辑频率均比基于rA1的BE3的碱基编辑频率高得多。因此，在BE中使用hA3A作为脱氨酶模块通常可以在高甲基化水平的基因组区域中实现较高的碱基编辑效率。

在GpC环境中发现基于rA1的BE对胞嘧啶的碱基编辑通常是低效的。同时，该实施例发现，在内源性和诱导性高甲基化背景下(图5e)，hA3A-BE3可以诱导在GpC位点的大多数胞嘧啶上有效的碱基编辑。该实施例进一步比较了它们在内源性和诱导性低甲基化背景下的编辑效率，并且观察到在GpC环境中(图5g，h)hA3A-BE3在编辑胞嘧啶方面和BE3的优越性相似。统计分析证实，在GpC环境中，无论是高甲基化(中位数约为2.3倍，P＝1×10^-5)还是低甲基化(中位数约为1.8倍,P＝6×10^-9)条件下，hA3A-BE3诱导的碱基编辑效率均显著高于BE3。值得注意的是，在所有测试的低甲基化区域中，hA3A-BE3诱导的碱基编辑对非GpC环境中的胞嘧啶与BE3一样有效(中位约为1.1倍，P＝0.045)。该示例还发现，在高甲基化水平(hA3A-BE3的中位数约为97％，对比BE3约为94％，P＝3×10-4)和低甲基化区域(hA3A-BE3的中位数约为92％，对比BE3中位数约为90％，P＝4×10-6)，hA3A-BE3诱导的非C至T转化率均低于BE3。BE3和hA3A-BE3都在甲基化水平高的CpG位点诱导的非C至T转化率要比甲基化水平低的CpG位点诱导的少(中位数约95％对比BE3约90％,P＝3×10^-5，和中位数约95％对比hA3A-BE3约92％,P＝5×10^-4)。该实施例还发现，hA3A-BE3诱导的***缺失频率比BE3高(在高和低甲基化区域中位数均约为2)。这种增加可能是因为hA3A的高脱氨酶活性引起的，它可以触发下游DNA修复途径以产生DNA双链断裂。

结果表明，hA3A-BE3可以在更广泛的范围(图5)内有效地诱导碱基编辑。但是，hA3A-BE3的编辑窗口(sgRNA靶位点的约12nt，位点2-13)比BE3(约5nt，位点4-8)更宽。由于hA3A-BE3的宽编辑窗口可能是由于hA3A的高脱氨酶活性引起的，因此可以降低hA3A突变中的脱氨酶活性可能会相应地缩小hA3A-BE3的编辑窗口。指定的突变(Y130F、D131Y或Y132D)成功地缩小了编辑窗口，对碱基编辑效率几乎没有影响，而锌配位基序中的突变几乎完全消除了脱氨酶活性(C101S和C106S)。

该实施例重点在于两个工程化改造的hA3A-BE3(hA3A-BE3-Y130F和hA3A-BE3-Y132D)，与BE3(位点4-8)相比，它们具有相似的编辑窗口(hA3A-BE3-Y130F的3-8位点和hA3A-BE3-Y132D的3-7位点)。在高甲基化的区域中，hA3A-BE3-Y130F和hA3A-BE3-Y132D在重叠的编辑窗口(位点4-7)(图6a：胞嘧啶为粉色和图6b：hA3A-BE3-Y130F中位数约为2.3倍，P＝0.002；hA3A-BE3-Y132D中位数约为1.2倍，P＝0.03)中的所有可编辑位点都能诱导出比BE3更高的编辑效率。对于重叠编辑窗口之外的胞嘧啶，hA3A-BE3-Y132D诱导了类似于BE3的C至T编辑频率，而hA3A-BE3-Y130F诱导了更高的编辑频率(图6a，黑色为胞嘧啶)。与原始的hA3A-BE3相似，在重叠的编辑窗口中(图6c，d，hA3A-BE3-Y130F中位约为2.3倍，P＝3×10^-5，对于hA3A-BE3-Y132D，中位数约为1.9倍，P＝0.002)，工程化改造的hA3A-BE3-Y130F和hA3A-BE3-Y132D在GpC环境中对胞嘧啶的编辑比BE3更有效。虽然两个工程化改造的hA3A-BE诱导了更高的C至T编辑效率(图6b，d)，但hA3A-BE3-Y130F和hA3A-BE3-Y132D的蛋白质表达水平与BE3非常相似(图6e)。在产物纯度方面，我们发现hA3A-BE3-Y130F产生的非C-T转化率较低(高甲基化区域：hA3A-BE3-Y130F的中位数约为96.3％，对比BE3约为95.6％，P＝0.03，低甲基化区域：hA3A-BE3-Y130F的中位数约为92％，对比BE3约为90％，P＝0.002)，但***缺失比BE3更多(高甲基化区域中位数约为2.1倍，P＝0.0002，低甲基化区域中位数约为1.3，P＝0.12)。在天然低甲基化区域中，hA3A-BE3-Y132D诱导的产物纯度高于BE3(hA3A-BE3-Y132D中位数约为93％，对比BE3中位数约为90％，P＝0.001)，而在天然高甲基化区域则较低(hA3A-BE3-Y132D的中位数约为94.9％，对比BE3的中位数约为95.6％，P＝0.03)。尽管如此，在所有测试位点，hA3A-BE3-Y132D诱导的***缺失频率与BE3诱导的***缺失频率相当(在高和低甲基化区域中中位数约为1.2倍)。

为了进一步增强C至T碱基编辑系统，将三个拷贝的3A-尿嘧啶DNA糖基化酶抑制剂(UGI)序列与hA3A-BE3-Y130F和hA3A-BE3-Y132D的C端融合产生hA3A-eBE-Y130F和hA3A-eBE-Y132D。在低甲基化区域中，与hA3A-BE3-Y130F和hA3A-BE3-Y132D相比，hA3A-eBE-Y130F和hA3A-eBE-Y132D分别带来显著更高的编辑效率(图6f、g：hA3A-eBE-Y130F的中位数约为1.2倍，P＝0.0004，hA3A-eBE-Y132D中值约为1.2倍，P＝0.004)和纯度更高的产物(图6h，hA3A-eBE-Y130F的中位数约为96％，而hA3A-BE3-Y130F的中位数约为94％，P＝0.006，hA3A-eBE-Y132D的中位数约为96％而hA3A-BE3-Y132D中位数约为92％，P＝0.004)和更低的***缺失频率(图6i：hA3A-eBE-Y130F的中位降低约21％，P＝4×10^-5，hA3A-eBE-Y132D的中位数降低约9％，P＝0.03)。在高甲基化区域，与hA3A-BE3-Y130F和hA3A-BE3-Y132D相比，hA3A-eBE-Y130F和hA3A-eBE-Y132D诱导显著更高纯度的产物(hA3A-eBE-Y130F的中位数约为97％，而hA3A-BE3-Y130F的中位数约为95％，P＝0.003，hA3A-eBE-Y132D中位数约为97％，而hA3A-BE3-Y132D中位数约为95％，P＝0.003)和较低的***缺失频率(hA3A-eBE-Y130F和中位数降低约23％，P＝2×10^-7，hA3A-eBE-Y132D的中位数降低约21％,P＝4×10^-5)但编辑效率保持不变(hA3A-eBE-Y130F和hA3A-eBE-Y132D的中位数约为二者的一倍)。总之，在所有测定背景下，这些结果表明与原始hA3A-BE3相比，hA3A-BE3-Y130F、hA3A-BE3-Y132D、hA3A-eBE-Y130F和hA3A-eBE-Y132D可以在变窄的编辑窗口中调节高效的碱基编辑。

在此，该实施例证明了hA3A-BE3及其工程化形式可以在所有检测的背景下包括甲基化的DNA区域和GpC二核苷酸中全面诱导有效的碱基编辑。为进一步扩大碱基编辑的范围，预计hA3A也可以与其他Cas蛋白缀合。

实施例3：使用dCas12a-hA3A碱基编辑器对人DYRK1A进行基因编辑

该实例测试了结合Cas12a(Cpf1)和各种突变型人类A3A蛋白的碱基编辑器。

方法

dCas12a-hA3A-BE表达载体的构建

使用合适的引物和pUC57-hA3A(由Genscript Biotechnology Co.，Ltd.合成)模板进行PCR得到hA3A的编码序列，并且对两端与线性载体同源的片段通过凝胶电泳纯化。凝胶电泳纯化后，通过质粒重组试剂盒克隆将片段结合到经SacI和SmaI线性化的dCas12a-BE载体，以获得表达载体dCas12a-hA3A-BE。

dCas12a-hA3A-BE-W98Y表达载体的构建

使用dCas12a-hA3A-BE作为模板，扩增含W98Y突变的两个PCR产物和一个同源臂，以及具有线性载体的同源片段。通过凝胶电泳纯化后，使用plasmid recombinant kitClone将两个片段同时结合至经ApaI和SmaI线性化dCas12a-hA3A-BE载体，以获得表达载体dCas12a-hA3A-BE-W98Y。

同样地，使用同样方法获得表达载体dCas12a-hA3A-BE-W104A、dCas12a-hA3A-BE-P134Y、dCas12a-hA3A-BE-W98Y-W104A、dCas12a-hA3A-BE-W98Y-P134Y、dCas12a-hA3A-BE-P134Y、dCas12a-hA3A-BE-W98Y-W104A-Y130F、dCas12a-hA3A-BE-W98Y-W104A-Y132D、dCas12a-hA3A-BE-W104A-Y130F-P134Y和dCas12a-hA3A-BE-W104P134Y。相关序列见表1和表2。

gRNA表达质粒的构建

将核苷酸序列退火为引物，并且用T4DNA连接酶将退火的产物连接到经限制性核酸内切酶BsaI消化的gRNA表达载体pLb-Cas12a-pGL3-U6-sgRNA中，获得靶向人类DYRK1A位点的gRNA表达质粒sgDYRK1A。

真核细胞转染

sgDYRK1A和dCas12a-hA3A-BE、dCas12a-hA3A-BE-W98Y、dCas12a-hA3A-BE-W104A、dCas12a-hA3A-BE-P134Y、dCas12a-hA3A-BE-W98Y-W104A、dCas2a-hA3A-BE-W98Y-P134Y、dCas12a-hA3A-BE-W104A-P134Y、dCas12a-hA3A-BE-W98Y-W104A-Y130F、dCas12a-hA3A-BE-W98Y-W104A-Y132D、dCas12a-hA3A-BEW104A-Y130F-P134Y、dCas12a-hA3A-BE-W104A-Y132D-P134Y以0.68ug:1μg的比例混合到200μl Opti-MEM中，添加1.68μl LIPOFECTAMINEplus，并添加5.04μl LIPOFECTAMINELTX，室温静置5分钟。500μl DMEM(+10％FBS)培养液加至24孔板，转染HEK293T细胞160,000。12小时后，换成含有1％双抗体(花青素)的新鲜培养液孵育60小时后收获细胞。

Sanger测序结果的EditR分析

使用EditR软件(moriaritylab.shinyapps.io/editr_v10/)分析DNASanger测序结果。EditR是Sanger测序结果分析软件的网络版本，于2018年开发(Kluesner MG,NedveckDA,Lahr WS,et al.EditR:A Method to Quantify Base Editing from SangerSequencing[J].The CRISPR Journal,2018,1(3):239-250.)。EditR是一种简单、准确、高效的分析工具，通过使用Sanger测序信号处理基于sgRNA序列的DNA样品测序结果，并最终在sgRNA目标位点输出碱基编辑效率。

测序结果示如图11和12显示。EditR分析结果参见图7和8。Cas12a(cpf1)和常规的胞嘧啶脱氨酶A1(APOBEC1)融合时，显示出较低的效率(参见如图7B，每组的第一列)。而与hA3A野生型蛋白的结合却极大提高了编辑效率(参见第二列)。有趣的是，A3A的突变体W98Y、W104A、P134Y或每两个的组合，都能进一步提高编辑效率(图7)。另外，当A3A进一步包含突变体Y130F或Y132D时(图8)，例如Cas12a-A3A的编辑窗口可以变窄从而实现更精确的编辑。

实施例4：使用dCas12a-hA3A碱基编辑器对人类SITE6进行基因编辑

该实施例用人类基因SITE6测试了各种提及的碱基编辑器。

实验过程类似于实施例3。测序结果在图15和16中详细示出(实验数据经两次重复获得)。EditR分析结果在图9和10中示出。与实施例3一样，Cas12a-A3A编辑器比Cas12a-A1具有更高的编辑效率，并且A3A突变W98Y、W104A、P134Y或两者的组合进一步提高了编辑效率(图9)。而且，当突变体Y130F或Y132D进一步包含A3A时(图10)，如Cas12a-A3A的编辑窗口能通过变窄实现更精确的编辑。

实施例5.用dCas12a-hA3A碱基编辑器编辑人类RUNX1的基因

该实施例用人类基因RUNX1测试了各种提及的碱基编辑器。

实验过程与实施例3相似。测序结果在图17和18中详细示出(实验数据经过两次重复得到)。EditR分析结果参见图11和12。与实施例3一样，Cas12a-A3A编辑器比Cas12a-rA1的编辑效率更高，并且A3A突变W98Y、W104A、P134Y或两者的组合进一步提高了编辑效率(图11)。而且，当A3A中进一步包含突变体Y130F或Y132D时(图12)，例如Cas12a-A3A的编辑窗口能通过变窄实现更精确的编辑。

***

本公开内容不受限于所述具体实施方式的范围，所述特定实施方式旨在作为本公开内容的各个方面的单个说明，并且功能上等同的任何组合物或方法均在本公开内容的范围内。对于本领域技术人员显而易见的是，在不脱离本发明的精神或范围的情况下，可以对本发明的方法和组合物进行各种修改和改变。因此，本公开旨在覆盖本公开的修改和变型，只要它们落入所附权利要求及其等同物的范围内。

在本说明书中提及的所有出版物和专利申请都以引用的方式并入本文，就像每个独立的出版物或专利申请都被具体地和单独地指示以引用的方式并入本文一样。

SEQUENCE LISTING

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<120> 用于碱基编辑的融合蛋白

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Met Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Ser Pro Lys Lys Lys Arg

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Lys Val Glu Ala Ser Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly

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Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys

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Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu

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Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys

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Asp Leu Asn Pro Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu

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Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser

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Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg

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Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly

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Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe

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Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys

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Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp

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Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile

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Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro

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Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu

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Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys

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Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp

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Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu

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Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu

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Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His

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Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp

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Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu

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Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser

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Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp

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Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile

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Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu

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Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu

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Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu

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Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn

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Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile

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Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn

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Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys

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Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val

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Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu

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Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys

660 665 670

Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn

675 680 685

Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys

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Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp

705 710 715 720

Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln

725 730 735

Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala

740 745 750

Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val

755 760 765

Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala

770 775 780

Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg

785 790 795 800

Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu

805 810 815

Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr

820 825 830

Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu

835 840 845

Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln

850 855 860

Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser

865 870 875 880

Asp Lys Asn Arg Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val

885 890 895

Lys Lys Met Lys Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile

900 905 910

Thr Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu

915 920 925

Ser Glu Leu Asp Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr

930 935 940

Arg Gln Ile Thr Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn

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Thr Lys Tyr Asp Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile

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Thr Leu Lys Ser Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe

980 985 990

Tyr Lys Val Arg Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr

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Leu Asn Ala Val Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys

1010 1015 1020

Leu Glu Ser Glu Phe Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val

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Arg Lys Met Ile Ala Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr

1040 1045 1050

Ala Lys Tyr Phe Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr

1055 1060 1065

Glu Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile

1070 1075 1080

Glu Thr Asn Gly Glu Thr Gly Glu Ile Val Trp Asp Lys Gly Arg

1085 1090 1095

Asp Phe Ala Thr Val Arg Lys Val Leu Ser Met Pro Gln Val Asn

1100 1105 1110

Ile Val Lys Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu

1115 1120 1125

Ser Ile Leu Pro Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys

1130 1135 1140

Lys Asp Trp Asp Pro Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr

1145 1150 1155

Val Ala Tyr Ser Val Leu Val Val Ala Lys Val Glu Lys Gly Lys

1160 1165 1170

Ser Lys Lys Leu Lys Ser Val Lys Glu Leu Leu Gly Ile Thr Ile

1175 1180 1185

Met Glu Arg Ser Ser Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu

1190 1195 1200

Ala Lys Gly Tyr Lys Glu Val Lys Lys Asp Leu Ile Ile Lys Leu

1205 1210 1215

Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn Gly Arg Lys Arg Met

1220 1225 1230

Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu

1235 1240 1245

Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu

1250 1255 1260

Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe

1265 1270 1275

Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln Ile

1280 1285 1290

Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp

1295 1300 1305

Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg

1310 1315 1320

Glu Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu

1325 1330 1335

Gly Ala Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg

1340 1345 1350

Lys Arg Tyr Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile

1355 1360 1365

His Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser

1370 1375 1380

Gln Leu Gly Gly Asp Ser Pro Lys Lys Lys Arg Lys Val Glu Ala

1385 1390 1395

Ser

<210> 12

<211> 83

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 12

Thr Asn Leu Ser Asp Ile Ile Glu Lys Glu Thr Gly Lys Gln Leu Val

1 5 10 15

Ile Gln Glu Ser Ile Leu Met Leu Pro Glu Glu Val Glu Glu Val Ile

20 25 30

Gly Asn Lys Pro Glu Ser Asp Ile Leu Val His Thr Ala Tyr Asp Glu

35 40 45

Ser Thr Asp Glu Asn Val Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr

50 55 60

Lys Pro Trp Ala Leu Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile

65 70 75 80

Lys Met Leu

<210> 13

<211> 16

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 13

Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser

1 5 10 15

<210> 14

<211> 4

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 14

Ser Gly Gly Ser

1

<210> 15

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 15

Pro Lys Lys Lys Arg Lys Val

1 5

<210> 16

<211> 1680

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 16

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn Ser Gly Ser Glu Thr Pro Gly Thr Ser

195 200 205

Glu Ser Ala Thr Pro Glu Ser Asp Lys Lys Tyr Ser Ile Gly Leu Ala

210 215 220

Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys

225 230 235 240

Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp Arg His Ser

245 250 255

Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr

260 265 270

Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg

275 280 285

Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met

290 295 300

Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu Ser Phe Leu

305 310 315 320

Val Glu Glu Asp Lys Lys His Glu Arg His Pro Ile Phe Gly Asn Ile

325 330 335

Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile Tyr His Leu

340 345 350

Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile

355 360 365

Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His Phe Leu Ile

370 375 380

Glu Gly Asp Leu Asn Pro Asp Asn Ser Asp Val Asp Lys Leu Phe Ile

385 390 395 400

Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn

405 410 415

Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys

420 425 430

Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys

435 440 445

Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro

450 455 460

Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu

465 470 475 480

Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile

485 490 495

Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp

500 505 510

Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile Thr Lys

515 520 525

Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His His Gln

530 535 540

Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro Glu Lys

545 550 555 560

Tyr Lys Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr

565 570 575

Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro

580 585 590

Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys Leu Asn

595 600 605

Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile

610 615 620

Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg Arg Gln

625 630 635 640

Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys

645 650 655

Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly

660 665 670

Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr Ile Thr

675 680 685

Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala Gln Ser

690 695 700

Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys

705 710 715 720

Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn

725 730 735

Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys Pro Ala

740 745 750

Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu Phe Lys

755 760 765

Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys

770 775 780

Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp Arg

785 790 795 800

Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile Lys

805 810 815

Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp

820 825 830

Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu Glu

835 840 845

Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys Gln

850 855 860

Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu

865 870 875 880

Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe

885 890 895

Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile His

900 905 910

Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser

915 920 925

Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly Ser

930 935 940

Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu

945 950 955 960

Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu

965 970 975

Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg

980 985 990

Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln

995 1000 1005

Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu

1010 1015 1020

Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val

1025 1030 1035

Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp

1040 1045 1050

His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn

1055 1060 1065

Lys Val Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn

1070 1075 1080

Val Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg

1085 1090 1095

Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn

1100 1105 1110

Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala

1115 1120 1125

Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys

1130 1135 1140

His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp

1145 1150 1155

Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys

1160 1165 1170

Ser Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys

1175 1180 1185

Val Arg Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu

1190 1195 1200

Asn Ala Val Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu

1205 1210 1215

Glu Ser Glu Phe Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg

1220 1225 1230

Lys Met Ile Ala Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala

1235 1240 1245

Lys Tyr Phe Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu

1250 1255 1260

Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu

1265 1270 1275

Thr Asn Gly Glu Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp

1280 1285 1290

Phe Ala Thr Val Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile

1295 1300 1305

Val Lys Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser

1310 1315 1320

Ile Leu Pro Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys

1325 1330 1335

Asp Trp Asp Pro Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val

1340 1345 1350

Ala Tyr Ser Val Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser

1355 1360 1365

Lys Lys Leu Lys Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met

1370 1375 1380

Glu Arg Ser Ser Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala

1385 1390 1395

Lys Gly Tyr Lys Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro

1400 1405 1410

Lys Tyr Ser Leu Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu

1415 1420 1425

Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro

1430 1435 1440

Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys

1445 1450 1455

Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val

1460 1465 1470

Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser

1475 1480 1485

Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys

1490 1495 1500

Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu

1505 1510 1515

Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly

1520 1525 1530

Ala Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys

1535 1540 1545

Arg Tyr Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His

1550 1555 1560

Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln

1565 1570 1575

Leu Gly Gly Asp Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile

1580 1585 1590

Glu Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu

1595 1600 1605

Met Leu Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu

1610 1615 1620

Ser Asp Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu

1625 1630 1635

Asn Val Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp

1640 1645 1650

Ala Leu Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met

1655 1660 1665

Leu Ser Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1670 1675 1680

<210> 17

<211> 1680

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 17

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Phe Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn Ser Gly Ser Glu Thr Pro Gly Thr Ser

195 200 205

Glu Ser Ala Thr Pro Glu Ser Asp Lys Lys Tyr Ser Ile Gly Leu Ala

210 215 220

Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys

225 230 235 240

Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp Arg His Ser

245 250 255

Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr

260 265 270

Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg

275 280 285

Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met

290 295 300

Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu Ser Phe Leu

305 310 315 320

Val Glu Glu Asp Lys Lys His Glu Arg His Pro Ile Phe Gly Asn Ile

325 330 335

Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile Tyr His Leu

340 345 350

Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile

355 360 365

Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His Phe Leu Ile

370 375 380

Glu Gly Asp Leu Asn Pro Asp Asn Ser Asp Val Asp Lys Leu Phe Ile

385 390 395 400

Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn

405 410 415

Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys

420 425 430

Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys

435 440 445

Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro

450 455 460

Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu

465 470 475 480

Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile

485 490 495

Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp

500 505 510

Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile Thr Lys

515 520 525

Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His His Gln

530 535 540

Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro Glu Lys

545 550 555 560

Tyr Lys Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr

565 570 575

Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro

580 585 590

Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys Leu Asn

595 600 605

Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile

610 615 620

Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg Arg Gln

625 630 635 640

Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys

645 650 655

Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly

660 665 670

Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr Ile Thr

675 680 685

Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala Gln Ser

690 695 700

Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys

705 710 715 720

Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn

725 730 735

Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys Pro Ala

740 745 750

Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu Phe Lys

755 760 765

Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys

770 775 780

Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp Arg

785 790 795 800

Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile Lys

805 810 815

Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp

820 825 830

Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu Glu

835 840 845

Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys Gln

850 855 860

Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu

865 870 875 880

Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe

885 890 895

Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile His

900 905 910

Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser

915 920 925

Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly Ser

930 935 940

Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu

945 950 955 960

Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu

965 970 975

Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg

980 985 990

Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln

995 1000 1005

Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu

1010 1015 1020

Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val

1025 1030 1035

Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp

1040 1045 1050

His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn

1055 1060 1065

Lys Val Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn

1070 1075 1080

Val Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg

1085 1090 1095

Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn

1100 1105 1110

Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala

1115 1120 1125

Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys

1130 1135 1140

His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp

1145 1150 1155

Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys

1160 1165 1170

Ser Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys

1175 1180 1185

Val Arg Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu

1190 1195 1200

Asn Ala Val Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu

1205 1210 1215

Glu Ser Glu Phe Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg

1220 1225 1230

Lys Met Ile Ala Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala

1235 1240 1245

Lys Tyr Phe Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu

1250 1255 1260

Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu

1265 1270 1275

Thr Asn Gly Glu Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp

1280 1285 1290

Phe Ala Thr Val Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile

1295 1300 1305

Val Lys Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser

1310 1315 1320

Ile Leu Pro Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys

1325 1330 1335

Asp Trp Asp Pro Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val

1340 1345 1350

Ala Tyr Ser Val Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser

1355 1360 1365

Lys Lys Leu Lys Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met

1370 1375 1380

Glu Arg Ser Ser Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala

1385 1390 1395

Lys Gly Tyr Lys Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro

1400 1405 1410

Lys Tyr Ser Leu Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu

1415 1420 1425

Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro

1430 1435 1440

Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys

1445 1450 1455

Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val

1460 1465 1470

Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser

1475 1480 1485

Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys

1490 1495 1500

Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu

1505 1510 1515

Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly

1520 1525 1530

Ala Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys

1535 1540 1545

Arg Tyr Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His

1550 1555 1560

Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln

1565 1570 1575

Leu Gly Gly Asp Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile

1580 1585 1590

Glu Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu

1595 1600 1605

Met Leu Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu

1610 1615 1620

Ser Asp Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu

1625 1630 1635

Asn Val Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp

1640 1645 1650

Ala Leu Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met

1655 1660 1665

Leu Ser Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1670 1675 1680

<210> 18

<211> 1680

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 18

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Asp Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn Ser Gly Ser Glu Thr Pro Gly Thr Ser

195 200 205

Glu Ser Ala Thr Pro Glu Ser Asp Lys Lys Tyr Ser Ile Gly Leu Ala

210 215 220

Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys

225 230 235 240

Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp Arg His Ser

245 250 255

Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr

260 265 270

Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg

275 280 285

Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met

290 295 300

Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu Ser Phe Leu

305 310 315 320

Val Glu Glu Asp Lys Lys His Glu Arg His Pro Ile Phe Gly Asn Ile

325 330 335

Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile Tyr His Leu

340 345 350

Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile

355 360 365

Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His Phe Leu Ile

370 375 380

Glu Gly Asp Leu Asn Pro Asp Asn Ser Asp Val Asp Lys Leu Phe Ile

385 390 395 400

Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn

405 410 415

Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys

420 425 430

Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys

435 440 445

Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro

450 455 460

Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu

465 470 475 480

Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile

485 490 495

Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp

500 505 510

Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile Thr Lys

515 520 525

Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His His Gln

530 535 540

Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro Glu Lys

545 550 555 560

Tyr Lys Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr

565 570 575

Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro

580 585 590

Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys Leu Asn

595 600 605

Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile

610 615 620

Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg Arg Gln

625 630 635 640

Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys

645 650 655

Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly

660 665 670

Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr Ile Thr

675 680 685

Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala Gln Ser

690 695 700

Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys

705 710 715 720

Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn

725 730 735

Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys Pro Ala

740 745 750

Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu Phe Lys

755 760 765

Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys

770 775 780

Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp Arg

785 790 795 800

Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile Lys

805 810 815

Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp

820 825 830

Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu Glu

835 840 845

Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys Gln

850 855 860

Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu

865 870 875 880

Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe

885 890 895

Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile His

900 905 910

Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser

915 920 925

Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly Ser

930 935 940

Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu

945 950 955 960

Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu

965 970 975

Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg

980 985 990

Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln

995 1000 1005

Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu

1010 1015 1020

Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val

1025 1030 1035

Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp

1040 1045 1050

His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn

1055 1060 1065

Lys Val Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn

1070 1075 1080

Val Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg

1085 1090 1095

Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn

1100 1105 1110

Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala

1115 1120 1125

Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys

1130 1135 1140

His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp

1145 1150 1155

Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys

1160 1165 1170

Ser Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys

1175 1180 1185

Val Arg Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu

1190 1195 1200

Asn Ala Val Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu

1205 1210 1215

Glu Ser Glu Phe Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg

1220 1225 1230

Lys Met Ile Ala Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala

1235 1240 1245

Lys Tyr Phe Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu

1250 1255 1260

Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu

1265 1270 1275

Thr Asn Gly Glu Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp

1280 1285 1290

Phe Ala Thr Val Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile

1295 1300 1305

Val Lys Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser

1310 1315 1320

Ile Leu Pro Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys

1325 1330 1335

Asp Trp Asp Pro Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val

1340 1345 1350

Ala Tyr Ser Val Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser

1355 1360 1365

Lys Lys Leu Lys Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met

1370 1375 1380

Glu Arg Ser Ser Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala

1385 1390 1395

Lys Gly Tyr Lys Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro

1400 1405 1410

Lys Tyr Ser Leu Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu

1415 1420 1425

Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro

1430 1435 1440

Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys

1445 1450 1455

Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val

1460 1465 1470

Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser

1475 1480 1485

Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys

1490 1495 1500

Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu

1505 1510 1515

Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly

1520 1525 1530

Ala Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys

1535 1540 1545

Arg Tyr Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His

1550 1555 1560

Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln

1565 1570 1575

Leu Gly Gly Asp Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile

1580 1585 1590

Glu Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu

1595 1600 1605

Met Leu Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu

1610 1615 1620

Ser Asp Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu

1625 1630 1635

Asn Val Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp

1640 1645 1650

Ala Leu Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met

1655 1660 1665

Leu Ser Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1670 1675 1680

<210> 19

<211> 1680

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 19

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn Ser Gly Ser Glu Thr Pro Gly Thr Ser

195 200 205

Glu Ser Ala Thr Pro Glu Ser Asp Lys Lys Tyr Ser Ile Gly Leu Ala

210 215 220

Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys

225 230 235 240

Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp Arg His Ser

245 250 255

Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr

260 265 270

Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg

275 280 285

Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met

290 295 300

Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu Ser Phe Leu

305 310 315 320

Val Glu Glu Asp Lys Lys His Glu Arg His Pro Ile Phe Gly Asn Ile

325 330 335

Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile Tyr His Leu

340 345 350

Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile

355 360 365

Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His Phe Leu Ile

370 375 380

Glu Gly Asp Leu Asn Pro Asp Asn Ser Asp Val Asp Lys Leu Phe Ile

385 390 395 400

Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn

405 410 415

Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys

420 425 430

Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys

435 440 445

Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro

450 455 460

Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu

465 470 475 480

Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile

485 490 495

Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp

500 505 510

Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile Thr Lys

515 520 525

Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His His Gln

530 535 540

Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro Glu Lys

545 550 555 560

Tyr Lys Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr

565 570 575

Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro

580 585 590

Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys Leu Asn

595 600 605

Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile

610 615 620

Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg Arg Gln

625 630 635 640

Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys

645 650 655

Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly

660 665 670

Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr Ile Thr

675 680 685

Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala Gln Ser

690 695 700

Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys

705 710 715 720

Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn

725 730 735

Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys Pro Ala

740 745 750

Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu Phe Lys

755 760 765

Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys

770 775 780

Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp Arg

785 790 795 800

Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile Lys

805 810 815

Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp

820 825 830

Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu Glu

835 840 845

Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys Gln

850 855 860

Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu

865 870 875 880

Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe

885 890 895

Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile His

900 905 910

Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser

915 920 925

Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly Ser

930 935 940

Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu

945 950 955 960

Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu

965 970 975

Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg

980 985 990

Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln

995 1000 1005

Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu

1010 1015 1020

Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val

1025 1030 1035

Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp

1040 1045 1050

His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn

1055 1060 1065

Lys Val Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn

1070 1075 1080

Val Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg

1085 1090 1095

Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn

1100 1105 1110

Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala

1115 1120 1125

Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys

1130 1135 1140

His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp

1145 1150 1155

Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys

1160 1165 1170

Ser Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys

1175 1180 1185

Val Arg Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu

1190 1195 1200

Asn Ala Val Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu

1205 1210 1215

Glu Ser Glu Phe Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg

1220 1225 1230

Lys Met Ile Ala Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala

1235 1240 1245

Lys Tyr Phe Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu

1250 1255 1260

Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu

1265 1270 1275

Thr Asn Gly Glu Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp

1280 1285 1290

Phe Ala Thr Val Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile

1295 1300 1305

Val Lys Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser

1310 1315 1320

Ile Leu Pro Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys

1325 1330 1335

Asp Trp Asp Pro Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val

1340 1345 1350

Ala Tyr Ser Val Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser

1355 1360 1365

Lys Lys Leu Lys Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met

1370 1375 1380

Glu Arg Ser Ser Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala

1385 1390 1395

Lys Gly Tyr Lys Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro

1400 1405 1410

Lys Tyr Ser Leu Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu

1415 1420 1425

Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro

1430 1435 1440

Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys

1445 1450 1455

Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val

1460 1465 1470

Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser

1475 1480 1485

Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys

1490 1495 1500

Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu

1505 1510 1515

Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly

1520 1525 1530

Ala Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys

1535 1540 1545

Arg Tyr Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His

1550 1555 1560

Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln

1565 1570 1575

Leu Gly Gly Asp Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile

1580 1585 1590

Glu Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu

1595 1600 1605

Met Leu Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu

1610 1615 1620

Ser Asp Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu

1625 1630 1635

Asn Val Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp

1640 1645 1650

Ala Leu Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met

1655 1660 1665

Leu Ser Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1670 1675 1680

<210> 20

<211> 1680

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 20

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Tyr Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn Ser Gly Ser Glu Thr Pro Gly Thr Ser

195 200 205

Glu Ser Ala Thr Pro Glu Ser Asp Lys Lys Tyr Ser Ile Gly Leu Ala

210 215 220

Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys

225 230 235 240

Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp Arg His Ser

245 250 255

Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr

260 265 270

Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg

275 280 285

Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met

290 295 300

Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu Ser Phe Leu

305 310 315 320

Val Glu Glu Asp Lys Lys His Glu Arg His Pro Ile Phe Gly Asn Ile

325 330 335

Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile Tyr His Leu

340 345 350

Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile

355 360 365

Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His Phe Leu Ile

370 375 380

Glu Gly Asp Leu Asn Pro Asp Asn Ser Asp Val Asp Lys Leu Phe Ile

385 390 395 400

Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn

405 410 415

Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys

420 425 430

Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys

435 440 445

Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro

450 455 460

Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu

465 470 475 480

Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile

485 490 495

Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp

500 505 510

Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile Thr Lys

515 520 525

Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His His Gln

530 535 540

Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro Glu Lys

545 550 555 560

Tyr Lys Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr

565 570 575

Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro

580 585 590

Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys Leu Asn

595 600 605

Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile

610 615 620

Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg Arg Gln

625 630 635 640

Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys

645 650 655

Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly

660 665 670

Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr Ile Thr

675 680 685

Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala Gln Ser

690 695 700

Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys

705 710 715 720

Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn

725 730 735

Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys Pro Ala

740 745 750

Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu Phe Lys

755 760 765

Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys

770 775 780

Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp Arg

785 790 795 800

Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile Lys

805 810 815

Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp

820 825 830

Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu Glu

835 840 845

Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys Gln

850 855 860

Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu

865 870 875 880

Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe

885 890 895

Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile His

900 905 910

Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser

915 920 925

Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly Ser

930 935 940

Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu

945 950 955 960

Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu

965 970 975

Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg

980 985 990

Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln

995 1000 1005

Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu

1010 1015 1020

Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val

1025 1030 1035

Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp

1040 1045 1050

His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn

1055 1060 1065

Lys Val Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn

1070 1075 1080

Val Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg

1085 1090 1095

Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn

1100 1105 1110

Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala

1115 1120 1125

Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys

1130 1135 1140

His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp

1145 1150 1155

Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys

1160 1165 1170

Ser Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys

1175 1180 1185

Val Arg Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu

1190 1195 1200

Asn Ala Val Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu

1205 1210 1215

Glu Ser Glu Phe Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg

1220 1225 1230

Lys Met Ile Ala Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala

1235 1240 1245

Lys Tyr Phe Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu

1250 1255 1260

Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu

1265 1270 1275

Thr Asn Gly Glu Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp

1280 1285 1290

Phe Ala Thr Val Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile

1295 1300 1305

Val Lys Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser

1310 1315 1320

Ile Leu Pro Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys

1325 1330 1335

Asp Trp Asp Pro Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val

1340 1345 1350

Ala Tyr Ser Val Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser

1355 1360 1365

Lys Lys Leu Lys Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met

1370 1375 1380

Glu Arg Ser Ser Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala

1385 1390 1395

Lys Gly Tyr Lys Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro

1400 1405 1410

Lys Tyr Ser Leu Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu

1415 1420 1425

Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro

1430 1435 1440

Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys

1445 1450 1455

Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val

1460 1465 1470

Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser

1475 1480 1485

Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys

1490 1495 1500

Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu

1505 1510 1515

Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly

1520 1525 1530

Ala Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys

1535 1540 1545

Arg Tyr Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His

1550 1555 1560

Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln

1565 1570 1575

Leu Gly Gly Asp Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile

1580 1585 1590

Glu Lys Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu

1595 1600 1605

Met Leu Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu

1610 1615 1620

Ser Asp Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu

1625 1630 1635

Asn Val Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp

1640 1645 1650

Ala Leu Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met

1655 1660 1665

Leu Ser Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1670 1675 1680

<210> 21

<211> 8442

<212> DNA

<213> Artificial Sequence

<220>

<223> 合成的

<400> 21

atatgccaag tacgccccct attgacgtca atgacggtaa atggcccgcc tggcattatg 60

cccagtacat gaccttatgg gactttccta cttggcagta catctacgta ttagtcatcg 120

ctattaccat ggtgatgcgg ttttggcagt acatcaatgg gcgtggatag cggtttgact 180

cacggggatt tccaagtctc caccccattg acgtcaatgg gagtttgttt tggcaccaaa 240

atcaacggga ctttccaaaa tgtcgtaaca actccgcccc attgacgcaa atgggcggta 300

ggcgtgtacg gtgggaggtc tatataagca gagctggttt agtgaaccgt cagatccgct 360

agagatccgc ggccgctaat acgactcact atagggagag ccgccaccat ggaagccagc 420

ccagcatccg ggcccagaca cttgatggat ccacacatat tcacttccaa ctttaacaat 480

ggcattggaa ggcataagac ctacctgtgc tacgaagtgg agcgcctgga caatggcacc 540

tcggtcaaga tggaccagca caggggcttt ctacacaacc aggctaagaa tcttctctgt 600

ggcttttacg gccgccatgc ggagctgcgc ttcttggacc tggttccttc tttgcagttg 660

gacccggccc agatctacag ggtcacttgg ttcatctcct ggagcccctg cttctcctgg 720

ggctgtgccg gggaagtgcg tgcgttcctt caggagaaca cacacgtgag actgcgtatc 780

ttcgctgccc gcatctatga ttacgacccc ctatataagg aggcactgca aatgctgcgg 840

gatgctgggg cccaagtctc catcatgacc tacgatgaat ttaagcactg ctgggacacc 900

tttgtggacc accagggatg tcccttccag ccctgggatg gactagatga gcacagccaa 960

gccctgagtg ggaggctgcg ggccattctc cagaatcagg gaaacagcgg cagcgagact 1020

cccgggacct cagagtccgc cacacccgaa agtgataaaa agtattctat tggtttagcc 1080

atcggcacta attccgttgg atgggctgtc ataaccgatg aatacaaagt accttcaaag 1140

aaatttaagg tgttggggaa cacagaccgt cattcgatta aaaagaatct tatcggtgcc 1200

ctcctattcg atagtggcga aacggcagag gcgactcgcc tgaaacgaac cgctcggaga 1260

aggtatacac gtcgcaagaa ccgaatatgt tacttacaag aaatttttag caatgagatg 1320

gccaaagttg acgattcttt ctttcaccgt ttggaagagt ccttccttgt cgaagaggac 1380

aagaaacatg aacggcaccc catctttgga aacatagtag atgaggtggc atatcatgaa 1440

aagtacccaa cgatttatca cctcagaaaa aagctagttg actcaactga taaagcggac 1500

ctgaggttaa tctacttggc tcttgcccat atgataaagt tccgtgggca ctttctcatt 1560

gagggtgatc taaatccgga caactcggat gtcgacaaac tgttcatcca gttagtacaa 1620

acctataatc agttgtttga agagaaccct ataaatgcaa gtggcgtgga tgcgaaggct 1680

attcttagcg cccgcctctc taaatcccga cggctagaaa acctgatcgc acaattaccc 1740

ggagagaaga aaaatgggtt gttcggtaac cttatagcgc tctcactagg cctgacacca 1800

aattttaagt cgaacttcga cttagctgaa gatgccaaat tgcagcttag taaggacacg 1860

tacgatgacg atctcgacaa tctactggca caaattggag atcagtatgc ggacttattt 1920

ttggctgcca aaaaccttag cgatgcaatc ctcctatctg acatactgag agttaatact 1980

gagattacca aggcgccgtt atccgcttca atgatcaaaa ggtacgatga acatcaccaa 2040

gacttgacac ttctcaaggc cctagtccgt cagcaactgc ctgagaaata taaggaaata 2100

ttctttgatc agtcgaaaaa cgggtacgca ggttatattg acggcggagc gagtcaagag 2160

gaattctaca agtttatcaa acccatatta gagaagatgg atgggacgga agagttgctt 2220

gtaaaactca atcgcgaaga tctactgcga aagcagcgga ctttcgacaa cggtagcatt 2280

ccacatcaaa tccacttagg cgaattgcat gctatactta gaaggcagga ggatttttat 2340

ccgttcctca aagacaatcg tgaaaagatt gagaaaatcc taacctttcg cataccttac 2400

tatgtgggac ccctggcccg agggaactct cggttcgcat ggatgacaag aaagtccgaa 2460

gaaacgatta ctccatggaa ttttgaggaa gttgtcgata aaggtgcgtc agctcaatcg 2520

ttcatcgaga ggatgaccaa ctttgacaag aatttaccga acgaaaaagt attgcctaag 2580

cacagtttac tttacgagta tttcacagtg tacaatgaac tcacgaaagt taagtatgtc 2640

actgagggca tgcgtaaacc cgcctttcta agcggagaac agaagaaagc aatagtagat 2700

ctgttattca agaccaaccg caaagtgaca gttaagcaat tgaaagagga ctactttaag 2760

aaaattgaat gcttcgattc tgtcgagatc tccggggtag aagatcgatt taatgcgtca 2820

cttggtacgt atcatgacct cctaaagata attaaagata aggacttcct ggataacgaa 2880

gagaatgaag atatcttaga agatatagtg ttgactctta ccctctttga agatcgggaa 2940

atgattgagg aaagactaaa aacatacgct cacctgttcg acgataaggt tatgaaacag 3000

ttaaagaggc gtcgctatac gggctgggga cgattgtcgc ggaaacttat caacgggata 3060

agagacaagc aaagtggtaa aactattctc gattttctaa agagcgacgg cttcgccaat 3120

aggaacttta tgcagctgat ccatgatgac tctttaacct tcaaagagga tatacaaaag 3180

gcacaggttt ccggacaagg ggactcattg cacgaacata ttgcgaatct tgctggttcg 3240

ccagccatca aaaagggcat actccagaca gtcaaagtag tggatgagct agttaaggtc 3300

atgggacgtc acaaaccgga aaacattgta atcgagatgg cacgcgaaaa tcaaacgact 3360

cagaaggggc aaaaaaacag tcgagagcgg atgaagagaa tagaagaggg tattaaagaa 3420

ctgggcagcc agatcttaaa ggagcatcct gtggaaaata cccaattgca gaacgagaaa 3480

ctttacctct attacctaca aaatggaagg gacatgtatg ttgatcagga actggacata 3540

aaccgtttat ctgattacga cgtcgatcac attgtacccc aatccttttt gaaggacgat 3600

tcaatcgaca ataaagtgct tacacgctcg gataagaacc gagggaaaag tgacaatgtt 3660

ccaagcgagg aagtcgtaaa gaaaatgaag aactattggc ggcagctcct aaatgcgaaa 3720

ctgataacgc aaagaaagtt cgataactta actaaagctg agaggggtgg cttgtctgaa 3780

cttgacaagg ccggatttat taaacgtcag ctcgtggaaa cccgccaaat cacaaagcat 3840

gttgcacaga tactagattc ccgaatgaat acgaaatacg acgagaacga taagctgatt 3900

cgggaagtca aagtaatcac tttaaagtca aaattggtgt cggacttcag aaaggatttt 3960

caattctata aagttaggga gataaataac taccaccatg cgcacgacgc ttatcttaat 4020

gccgtcgtag ggaccgcact cattaagaaa tacccgaagc tagaaagtga gtttgtgtat 4080

ggtgattaca aagtttatga cgtccgtaag atgatcgcga aaagcgaaca ggagataggc 4140

aaggctacag ccaaatactt cttttattct aacattatga atttctttaa gacggaaatc 4200

actctggcaa acggagagat acgcaaacga cctttaattg aaaccaatgg ggagacaggt 4260

gaaatcgtat gggataaggg ccgggacttc gcgacggtga gaaaagtttt gtccatgccc 4320

caagtcaaca tagtaaagaa aactgaggtg cagaccggag ggttttcaaa ggaatcgatt 4380

cttccaaaaa ggaatagtga taagctcatc gctcgtaaaa aggactggga cccgaaaaag 4440

tacggtggct tcgatagccc tacagttgcc tattctgtcc tagtagtggc aaaagttgag 4500

aagggaaaat ccaagaaact gaagtcagtc aaagaattat tggggataac gattatggag 4560

cgctcgtctt ttgaaaagaa ccccatcgac ttccttgagg cgaaaggtta caaggaagta 4620

aaaaaggatc tcataattaa actaccaaag tatagtctgt ttgagttaga aaatggccga 4680

aaacggatgt tggctagcgc cggagagctt caaaagggga acgaactcgc actaccgtct 4740

aaatacgtga atttcctgta tttagcgtcc cattacgaga agttgaaagg ttcacctgaa 4800

gataacgaac agaagcaact ttttgttgag cagcacaaac attatctcga cgaaatcata 4860

gagcaaattt cggaattcag taagagagtc atcctagctg atgccaatct ggacaaagta 4920

ttaagcgcat acaacaagca cagggataaa cccatacgtg agcaggcgga aaatattatc 4980

catttgttta ctcttaccaa cctcggcgct ccagccgcat tcaagtattt tgacacaacg 5040

atagatcgca aacgatacac ttctaccaag gaggtgctag acgcgacact gattcaccaa 5100

tccatcacgg gattatatga aactcggata gatttgtcac agcttggggg tgactctggt 5160

ggttctacta atctgtcaga tattattgaa aaggagaccg gtaagcaact ggttatccag 5220

gaatccatcc tcatgctccc agaggaggtg gaagaagtca ttgggaacaa gccggaaagc 5280

gatatactcg tgcacaccgc ctacgacgag agcaccgacg agaatgtcat gcttctgact 5340

agcgacgccc ctgaatacaa gccttgggct ctggtcatac aggatagcaa cggtgagaac 5400

aagattaaga tgctctctgg tggttctccc aagaagaaga ggaaagtcta accggtcatc 5460

atcaccatca ccattgagtt taaacccgct gatcagcctc gactgtgcct tctagttgcc 5520

agccatctgt tgtttgcccc tcccccgtgc cttccttgac cctggaaggt gccactccca 5580

ctgtcctttc ctaataaaat gaggaaattg catcgcattg tctgagtagg tgtcattcta 5640

ttctgggggg tggggtgggg caggacagca agggggagga ttgggaagac aatagcaggc 5700

atgctgggga tgcggtgggc tctatggctt ctgaggcgga aagaaccagc tggggctcga 5760

taccgtcgac ctctagctag agcttggcgt aatcatggtc atagctgttt cctgtgtgaa 5820

attgttatcc gctcacaatt ccacacaaca tacgagccgg aagcataaag tgtaaagcct 5880

agggtgccta atgagtgagc taactcacat taattgcgtt gcgctcactg cccgctttcc 5940

agtcgggaaa cctgtcgtgc cagctgcatt aatgaatcgg ccaacgcgcg gggagaggcg 6000

gtttgcgtat tgggcgctct tccgcttcct cgctcactga ctcgctgcgc tcggtcgttc 6060

ggctgcggcg agcggtatca gctcactcaa aggcggtaat acggttatcc acagaatcag 6120

gggataacgc aggaaagaac atgtgagcaa aaggccagca aaaggccagg aaccgtaaaa 6180

aggccgcgtt gctggcgttt ttccataggc tccgcccccc tgacgagcat cacaaaaatc 6240

gacgctcaag tcagaggtgg cgaaacccga caggactata aagataccag gcgtttcccc 6300

ctggaagctc cctcgtgcgc tctcctgttc cgaccctgcc gcttaccgga tacctgtccg 6360

cctttctccc ttcgggaagc gtggcgcttt ctcatagctc acgctgtagg tatctcagtt 6420

cggtgtaggt cgttcgctcc aagctgggct gtgtgcacga accccccgtt cagcccgacc 6480

gctgcgcctt atccggtaac tatcgtcttg agtccaaccc ggtaagacac gacttatcgc 6540

cactggcagc agccactggt aacaggatta gcagagcgag gtatgtaggc ggtgctacag 6600

agttcttgaa gtggtggcct aactacggct acactagaag aacagtattt ggtatctgcg 6660

ctctgctgaa gccagttacc ttcggaaaaa gagttggtag ctcttgatcc ggcaaacaaa 6720

ccaccgctgg tagcggtggt ttttttgttt gcaagcagca gattacgcgc agaaaaaaag 6780

gatctcaaga agatcctttg atcttttcta cggggtctga cgctcagtgg aacgaaaact 6840

cacgttaagg gattttggtc atgagattat caaaaaggat cttcacctag atccttttaa 6900

attaaaaatg aagttttaaa tcaatctaaa gtatatatga gtaaacttgg tctgacagtt 6960

accaatgctt aatcagtgag gcacctatct cagcgatctg tctatttcgt tcatccatag 7020

ttgcctgact ccccgtcgtg tagataacta cgatacggga gggcttacca tctggcccca 7080

gtgctgcaat gataccgcga gacccacgct caccggctcc agatttatca gcaataaacc 7140

agccagccgg aagggccgag cgcagaagtg gtcctgcaac tttatccgcc tccatccagt 7200

ctattaattg ttgccgggaa gctagagtaa gtagttcgcc agttaatagt ttgcgcaacg 7260

ttgttgccat tgctacaggc atcgtggtgt cacgctcgtc gtttggtatg gcttcattca 7320

gctccggttc ccaacgatca aggcgagtta catgatcccc catgttgtgc aaaaaagcgg 7380

ttagctcctt cggtcctccg atcgttgtca gaagtaagtt ggccgcagtg ttatcactca 7440

tggttatggc agcactgcat aattctctta ctgtcatgcc atccgtaaga tgcttttctg 7500

tgactggtga gtactcaacc aagtcattct gagaatagtg tatgcggcga ccgagttgct 7560

cttgcccggc gtcaatacgg gataataccg cgccacatag cagaacttta aaagtgctca 7620

tcattggaaa acgttcttcg gggcgaaaac tctcaaggat cttaccgctg ttgagatcca 7680

gttcgatgta acccactcgt gcacccaact gatcttcagc atcttttact ttcaccagcg 7740

tttctgggtg agcaaaaaca ggaaggcaaa atgccgcaaa aaagggaata agggcgacac 7800

ggaaatgttg aatactcata ctcttccttt ttcaatatta ttgaagcatt tatcagggtt 7860

attgtctcat gagcggatac atatttgaat gtatttagaa aaataaacaa ataggggttc 7920

cgcgcacatt tccccgaaaa gtgccacctg acgtcgacgg atcgggagat cgatctcccg 7980

atcccctagg gtcgactctc agtacaatct gctctgatgc cgcatagtta agccagtatc 8040

tgctccctgc ttgtgtgttg gaggtcgctg agtagtgcgc gagcaaaatt taagctacaa 8100

caaggcaagg cttgaccgac aattgcatga agaatctgct tagggttagg cgttttgcgc 8160

tgcttcgcga tgtacgggcc agatatacgc gttgacattg attattgact agttattaat 8220

agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc gttacataac 8280

ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa 8340

tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt 8400

atttacggta aactgcccac ttggcagtac atcaagtgta tc 8442

<210> 22

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 22

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Phe Glu Asp Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 23

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 23

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Phe Tyr Asp Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 24

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 24

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Tyr Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 25

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 25

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Tyr Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 26

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 26

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Tyr Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 27

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 27

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Tyr Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Tyr Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 28

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 28

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Tyr Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 29

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 29

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Tyr Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Phe Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 30

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 30

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Tyr Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Asp Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 31

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 31

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Phe Asp Tyr Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 32

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 32

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Asp Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 33

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 33

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Phe Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 34

<211> 199

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 34

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Leu Met Asp Pro His

1 5 10 15

Ile Phe Thr Ser Asn Phe Asn Asn Gly Ile Gly Arg His Lys Thr Tyr

20 25 30

Leu Cys Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met

35 40 45

Asp Gln His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys

50 55 60

Gly Phe Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro

65 70 75 80

Ser Leu Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile

85 90 95

Ser Trp Ser Pro Cys Phe Ser Ala Gly Cys Ala Gly Glu Val Arg Ala

100 105 110

Phe Leu Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg

115 120 125

Ile Tyr Asp Asp Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg

130 135 140

Asp Ala Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His

145 150 155 160

Cys Trp Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp

165 170 175

Asp Gly Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala

180 185 190

Ile Leu Gln Asn Gln Gly Asn

195

<210> 35

<211> 181

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 35

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Lys Thr Tyr Leu Cys

1 5 10 15

Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met Asp Gln

20 25 30

His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe

35 40 45

Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro Ser Leu

50 55 60

Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr

65 70 75 80

Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala Phe Leu

85 90 95

Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr

100 105 110

Asp Tyr Asp Pro Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg Asp Ala

115 120 125

Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His Cys Trp

130 135 140

Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly

145 150 155 160

Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu

165 170 175

Gln Asn Gln Gly Asn

180

<210> 36

<211> 181

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 36

Met Glu Ala Ser Pro Ala Ser Gly Pro Arg His Lys Thr Tyr Leu Cys

1 5 10 15

Tyr Glu Val Glu Arg Leu Asp Asn Gly Thr Ser Val Lys Met Asp Gln

20 25 30

His Arg Gly Phe Leu His Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe

35 40 45

Tyr Gly Arg His Ala Glu Leu Arg Phe Leu Asp Leu Val Pro Ser Leu

50 55 60

Gln Leu Asp Pro Ala Gln Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp

65 70 75 80

Ser Pro Cys Phe Ser Trp Gly Cys Ala Gly Glu Val Arg Ala Phe Leu

85 90 95

Gln Glu Asn Thr His Val Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr

100 105 110

Asp Tyr Asp Tyr Leu Tyr Lys Glu Ala Leu Gln Met Leu Arg Asp Ala

115 120 125

Gly Ala Gln Val Ser Ile Met Thr Tyr Asp Glu Phe Lys His Cys Trp

130 135 140

Asp Thr Phe Val Asp His Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly

145 150 155 160

Leu Asp Glu His Ser Gln Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu

165 170 175

Gln Asn Gln Gly Asn

180

<210> 37

<211> 1230

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 37

Met Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr

1 5 10 15

Leu Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp

20 25 30

Asn Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys

35 40 45

Gly Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp

50 55 60

Val Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu

65 70 75 80

Phe Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn

85 90 95

Leu Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn

100 105 110

Glu Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu

115 120 125

Pro Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe

130 135 140

Asn Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn

145 150 155 160

Met Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile

165 170 175

Asn Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys

180 185 190

Val Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys

195 200 205

Ile Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe

210 215 220

Phe Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile

225 230 235 240

Ile Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn

245 250 255

Glu Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys

260 265 270

Phe Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser

275 280 285

Phe Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe

290 295 300

Arg Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys

305 310 315 320

Leu Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile

325 330 335

Phe Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe

340 345 350

Gly Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp

355 360 365

Ile His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp

370 375 380

Arg Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu

385 390 395 400

Gln Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu

405 410 415

Ile Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser

420 425 430

Glu Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys

435 440 445

Asn Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys

450 455 460

Ser Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr

465 470 475 480

Asn Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile

485 490 495

Leu Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr

500 505 510

Gln Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro

515 520 525

Gln Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala

530 535 540

Thr Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys

545 550 555 560

Lys Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly

565 570 575

Asn Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met

580 585 590

Leu Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro

595 600 605

Ser Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly

610 615 620

Asp Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys

625 630 635 640

Asp Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn

645 650 655

Phe Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu

660 665 670

Val Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys

675 680 685

Glu Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile

690 695 700

Tyr Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His

705 710 715 720

Thr Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile

725 730 735

Arg Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys

740 745 750

Lys Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys

755 760 765

Asn Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr

770 775 780

Lys Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

785 790 795 800

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu Val

805 810 815

Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly Ile Ala

820 825 830

Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp Gly Lys Gly

835 840 845

Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile Asn Asn Phe Asn

850 855 860

Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu Leu Asp Lys Lys Glu

865 870 875 880

Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp Thr Ser Ile Glu Asn Ile

885 890 895

Lys Glu Leu Lys Ala Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys

900 905 910

Glu Leu Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Ala Asp Leu Asn

915 920 925

Ser Gly Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln

930 935 940

Lys Phe Glu Lys Met Leu Ile Asp Lys Leu Asn Tyr Met Val Asp Lys

945 950 955 960

Lys Ser Asn Pro Cys Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile

965 970 975

Thr Asn Lys Phe Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe

980 985 990

Ile Phe Tyr Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr

995 1000 1005

Gly Phe Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp

1010 1015 1020

Ser Lys Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro

1025 1030 1035

Glu Glu Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser

1040 1045 1050

Arg Thr Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr

1055 1060 1065

Gly Asn Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val

1070 1075 1080

Phe Asp Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu

1085 1090 1095

Phe Asn Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala

1100 1105 1110

Leu Leu Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met

1115 1120 1125

Ala Leu Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly

1130 1135 1140

Arg Thr Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp

1145 1150 1155

Gly Ile Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala

1160 1165 1170

Ile Leu Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala

1175 1180 1185

Arg Lys Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp

1190 1195 1200

Glu Lys Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp

1205 1210 1215

Leu Glu Tyr Ala Gln Thr Ser Val Lys His Gly Ser

1220 1225 1230

<210> 38

<211> 1307

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 38

Met Thr Gln Phe Glu Gly Phe Thr Asn Leu Tyr Gln Val Ser Lys Thr

1 5 10 15

Leu Arg Phe Glu Leu Ile Pro Gln Gly Lys Thr Leu Lys His Ile Gln

20 25 30

Glu Gln Gly Phe Ile Glu Glu Asp Lys Ala Arg Asn Asp His Tyr Lys

35 40 45

Glu Leu Lys Pro Ile Ile Asp Arg Ile Tyr Lys Thr Tyr Ala Asp Gln

50 55 60

Cys Leu Gln Leu Val Gln Leu Asp Trp Glu Asn Leu Ser Ala Ala Ile

65 70 75 80

Asp Ser Tyr Arg Lys Glu Lys Thr Glu Glu Thr Arg Asn Ala Leu Ile

85 90 95

Glu Glu Gln Ala Thr Tyr Arg Asn Ala Ile His Asp Tyr Phe Ile Gly

100 105 110

Arg Thr Asp Asn Leu Thr Asp Ala Ile Asn Lys Arg His Ala Glu Ile

115 120 125

Tyr Lys Gly Leu Phe Lys Ala Glu Leu Phe Asn Gly Lys Val Leu Lys

130 135 140

Gln Leu Gly Thr Val Thr Thr Thr Glu His Glu Asn Ala Leu Leu Arg

145 150 155 160

Ser Phe Asp Lys Phe Thr Thr Tyr Phe Ser Gly Phe Tyr Glu Asn Arg

165 170 175

Lys Asn Val Phe Ser Ala Glu Asp Ile Ser Thr Ala Ile Pro His Arg

180 185 190

Ile Val Gln Asp Asn Phe Pro Lys Phe Lys Glu Asn Cys His Ile Phe

195 200 205

Thr Arg Leu Ile Thr Ala Val Pro Ser Leu Arg Glu His Phe Glu Asn

210 215 220

Val Lys Lys Ala Ile Gly Ile Phe Val Ser Thr Ser Ile Glu Glu Val

225 230 235 240

Phe Ser Phe Pro Phe Tyr Asn Gln Leu Leu Thr Gln Thr Gln Ile Asp

245 250 255

Leu Tyr Asn Gln Leu Leu Gly Gly Ile Ser Arg Glu Ala Gly Thr Glu

260 265 270

Lys Ile Lys Gly Leu Asn Glu Val Leu Asn Leu Ala Ile Gln Lys Asn

275 280 285

Asp Glu Thr Ala His Ile Ile Ala Ser Leu Pro His Arg Phe Ile Pro

290 295 300

Leu Phe Lys Gln Ile Leu Ser Asp Arg Asn Thr Leu Ser Phe Ile Leu

305 310 315 320

Glu Glu Phe Lys Ser Asp Glu Glu Val Ile Gln Ser Phe Cys Lys Tyr

325 330 335

Lys Thr Leu Leu Arg Asn Glu Asn Val Leu Glu Thr Ala Glu Ala Leu

340 345 350

Phe Asn Glu Leu Asn Ser Ile Asp Leu Thr His Ile Phe Ile Ser His

355 360 365

Lys Lys Leu Glu Thr Ile Ser Ser Ala Leu Cys Asp His Trp Asp Thr

370 375 380

Leu Arg Asn Ala Leu Tyr Glu Arg Arg Ile Ser Glu Leu Thr Gly Lys

385 390 395 400

Ile Thr Lys Ser Ala Lys Glu Lys Val Gln Arg Ser Leu Lys His Glu

405 410 415

Asp Ile Asn Leu Gln Glu Ile Ile Ser Ala Ala Gly Lys Glu Leu Ser

420 425 430

Glu Ala Phe Lys Gln Lys Thr Ser Glu Ile Leu Ser His Ala His Ala

435 440 445

Ala Leu Asp Gln Pro Leu Pro Thr Thr Leu Lys Lys Gln Glu Glu Lys

450 455 460

Glu Ile Leu Lys Ser Gln Leu Asp Ser Leu Leu Gly Leu Tyr His Leu

465 470 475 480

Leu Asp Trp Phe Ala Val Asp Glu Ser Asn Glu Val Asp Pro Glu Phe

485 490 495

Ser Ala Arg Leu Thr Gly Ile Lys Leu Glu Met Glu Pro Ser Leu Ser

500 505 510

Phe Tyr Asn Lys Ala Arg Asn Tyr Ala Thr Lys Lys Pro Tyr Ser Val

515 520 525

Glu Lys Phe Lys Leu Asn Phe Gln Met Pro Thr Leu Ala Ser Gly Trp

530 535 540

Asp Val Asn Lys Glu Lys Asn Asn Gly Ala Ile Leu Phe Val Lys Asn

545 550 555 560

Gly Leu Tyr Tyr Leu Gly Ile Met Pro Lys Gln Lys Gly Arg Tyr Lys

565 570 575

Ala Leu Ser Phe Glu Pro Thr Glu Lys Thr Ser Glu Gly Phe Asp Lys

580 585 590

Met Tyr Tyr Asp Tyr Phe Pro Asp Ala Ala Lys Met Ile Pro Lys Cys

595 600 605

Ser Thr Gln Leu Lys Ala Val Thr Ala His Phe Gln Thr His Thr Thr

610 615 620

Pro Ile Leu Leu Ser Asn Asn Phe Ile Glu Pro Leu Glu Ile Thr Lys

625 630 635 640

Glu Ile Tyr Asp Leu Asn Asn Pro Glu Lys Glu Pro Lys Lys Phe Gln

645 650 655

Thr Ala Tyr Ala Lys Lys Thr Gly Asp Gln Lys Gly Tyr Arg Glu Ala

660 665 670

Leu Cys Lys Trp Ile Asp Phe Thr Arg Asp Phe Leu Ser Lys Tyr Thr

675 680 685

Lys Thr Thr Ser Ile Asp Leu Ser Ser Leu Arg Pro Ser Ser Gln Tyr

690 695 700

Lys Asp Leu Gly Glu Tyr Tyr Ala Glu Leu Asn Pro Leu Leu Tyr His

705 710 715 720

Ile Ser Phe Gln Arg Ile Ala Glu Lys Glu Ile Met Asp Ala Val Glu

725 730 735

Thr Gly Lys Leu Tyr Leu Phe Gln Ile Tyr Asn Lys Asp Phe Ala Lys

740 745 750

Gly His His Gly Lys Pro Asn Leu His Thr Leu Tyr Trp Thr Gly Leu

755 760 765

Phe Ser Pro Glu Asn Leu Ala Lys Thr Ser Ile Lys Leu Asn Gly Gln

770 775 780

Ala Glu Leu Phe Tyr Arg Pro Lys Ser Arg Met Lys Arg Met Ala His

785 790 795 800

Arg Leu Gly Glu Lys Met Leu Asn Lys Lys Leu Lys Asp Gln Lys Thr

805 810 815

Pro Ile Pro Asp Thr Leu Tyr Gln Glu Leu Tyr Asp Tyr Val Asn His

820 825 830

Arg Leu Ser His Asp Leu Ser Asp Glu Ala Arg Ala Leu Leu Pro Asn

835 840 845

Val Ile Thr Lys Glu Val Ser His Glu Ile Ile Lys Asp Arg Arg Phe

850 855 860

Thr Ser Asp Lys Phe Phe Phe His Val Pro Ile Thr Leu Asn Tyr Gln

865 870 875 880

Ala Ala Asn Ser Pro Ser Lys Phe Asn Gln Arg Val Asn Ala Tyr Leu

885 890 895

Lys Glu His Pro Glu Thr Pro Ile Ile Gly Ile Asp Arg Gly Glu Arg

900 905 910

Asn Leu Ile Tyr Ile Thr Val Ile Asp Ser Thr Gly Lys Ile Leu Glu

915 920 925

Gln Arg Ser Leu Asn Thr Ile Gln Gln Phe Asp Tyr Gln Lys Lys Leu

930 935 940

Asp Asn Arg Glu Lys Glu Arg Val Ala Ala Arg Gln Ala Trp Ser Val

945 950 955 960

Val Gly Thr Ile Lys Asp Leu Lys Gln Gly Tyr Leu Ser Gln Val Ile

965 970 975

His Glu Ile Val Asp Leu Met Ile His Tyr Gln Ala Val Val Val Leu

980 985 990

Glu Asn Leu Asn Phe Gly Phe Lys Ser Lys Arg Thr Gly Ile Ala Glu

995 1000 1005

Lys Ala Val Tyr Gln Gln Phe Glu Lys Met Leu Ile Asp Lys Leu

1010 1015 1020

Asn Cys Leu Val Leu Lys Asp Tyr Pro Ala Glu Lys Val Gly Gly

1025 1030 1035

Val Leu Asn Pro Tyr Gln Leu Thr Asp Gln Phe Thr Ser Phe Ala

1040 1045 1050

Lys Met Gly Thr Gln Ser Gly Phe Leu Phe Tyr Val Pro Ala Pro

1055 1060 1065

Tyr Thr Ser Lys Ile Asp Pro Leu Thr Gly Phe Val Asp Pro Phe

1070 1075 1080

Val Trp Lys Thr Ile Lys Asn His Glu Ser Arg Lys His Phe Leu

1085 1090 1095

Glu Gly Phe Asp Phe Leu His Tyr Asp Val Lys Thr Gly Asp Phe

1100 1105 1110

Ile Leu His Phe Lys Met Asn Arg Asn Leu Ser Phe Gln Arg Gly

1115 1120 1125

Leu Pro Gly Phe Met Pro Ala Trp Asp Ile Val Phe Glu Lys Asn

1130 1135 1140

Glu Thr Gln Phe Asp Ala Lys Gly Thr Pro Phe Ile Ala Gly Lys

1145 1150 1155

Arg Ile Val Pro Val Ile Glu Asn His Arg Phe Thr Gly Arg Tyr

1160 1165 1170

Arg Asp Leu Tyr Pro Ala Asn Glu Leu Ile Ala Leu Leu Glu Glu

1175 1180 1185

Lys Gly Ile Val Phe Arg Asp Gly Ser Asn Ile Leu Pro Lys Leu

1190 1195 1200

Leu Glu Asn Asp Asp Ser His Ala Ile Asp Thr Met Val Ala Leu

1205 1210 1215

Ile Arg Ser Val Leu Gln Met Arg Asn Ser Asn Ala Ala Thr Gly

1220 1225 1230

Glu Asp Tyr Ile Asn Ser Pro Val Arg Asp Leu Asn Gly Val Cys

1235 1240 1245

Phe Asp Ser Arg Phe Gln Asn Pro Glu Trp Pro Met Asp Ala Asp

1250 1255 1260

Ala Asn Gly Ala Tyr His Ile Ala Leu Lys Gly Gln Leu Leu Leu

1265 1270 1275

Asn His Leu Lys Glu Ser Lys Asp Leu Lys Leu Gln Asn Gly Ile

1280 1285 1290

Ser Asn Gln Asp Trp Leu Ala Tyr Ile Gln Glu Leu Arg Asn

1295 1300 1305

<210> 39

<211> 1300

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 39

Met Ser Ile Tyr Gln Glu Phe Val Asn Lys Tyr Ser Leu Ser Lys Thr

1 5 10 15

Leu Arg Phe Glu Leu Ile Pro Gln Gly Lys Thr Leu Glu Asn Ile Lys

20 25 30

Ala Arg Gly Leu Ile Leu Asp Asp Glu Lys Arg Ala Lys Asp Tyr Lys

35 40 45

Lys Ala Lys Gln Ile Ile Asp Lys Tyr His Gln Phe Phe Ile Glu Glu

50 55 60

Ile Leu Ser Ser Val Cys Ile Ser Glu Asp Leu Leu Gln Asn Tyr Ser

65 70 75 80

Asp Val Tyr Phe Lys Leu Lys Lys Ser Asp Asp Asp Asn Leu Gln Lys

85 90 95

Asp Phe Lys Ser Ala Lys Asp Thr Ile Lys Lys Gln Ile Ser Glu Tyr

100 105 110

Ile Lys Asp Ser Glu Lys Phe Lys Asn Leu Phe Asn Gln Asn Leu Ile

115 120 125

Asp Ala Lys Lys Gly Gln Glu Ser Asp Leu Ile Leu Trp Leu Lys Gln

130 135 140

Ser Lys Asp Asn Gly Ile Glu Leu Phe Lys Ala Asn Ser Asp Ile Thr

145 150 155 160

Asp Ile Asp Glu Ala Leu Glu Ile Ile Lys Ser Phe Lys Gly Trp Thr

165 170 175

Thr Tyr Phe Lys Gly Phe His Glu Asn Arg Lys Asn Val Tyr Ser Ser

180 185 190

Asn Asp Ile Pro Thr Ser Ile Ile Tyr Arg Ile Val Asp Asp Asn Leu

195 200 205

Pro Lys Phe Leu Glu Asn Lys Ala Lys Tyr Glu Ser Leu Lys Asp Lys

210 215 220

Ala Pro Glu Ala Ile Asn Tyr Glu Gln Ile Lys Lys Asp Leu Ala Glu

225 230 235 240

Glu Leu Thr Phe Asp Ile Asp Tyr Lys Thr Ser Glu Val Asn Gln Arg

245 250 255

Val Phe Ser Leu Asp Glu Val Phe Glu Ile Ala Asn Phe Asn Asn Tyr

260 265 270

Leu Asn Gln Ser Gly Ile Thr Lys Phe Asn Thr Ile Ile Gly Gly Lys

275 280 285

Phe Val Asn Gly Glu Asn Thr Lys Arg Lys Gly Ile Asn Glu Tyr Ile

290 295 300

Asn Leu Tyr Ser Gln Gln Ile Asn Asp Lys Thr Leu Lys Lys Tyr Lys

305 310 315 320

Met Ser Val Leu Phe Lys Gln Ile Leu Ser Asp Thr Glu Ser Lys Ser

325 330 335

Phe Val Ile Asp Lys Leu Glu Asp Asp Ser Asp Val Val Thr Thr Met

340 345 350

Gln Ser Phe Tyr Glu Gln Ile Ala Ala Phe Lys Thr Val Glu Glu Lys

355 360 365

Ser Ile Lys Glu Thr Leu Ser Leu Leu Phe Asp Asp Leu Lys Ala Gln

370 375 380

Lys Leu Asp Leu Ser Lys Ile Tyr Phe Lys Asn Asp Lys Ser Leu Thr

385 390 395 400

Asp Leu Ser Gln Gln Val Phe Asp Asp Tyr Ser Val Ile Gly Thr Ala

405 410 415

Val Leu Glu Tyr Ile Thr Gln Gln Ile Ala Pro Lys Asn Leu Asp Asn

420 425 430

Pro Ser Lys Lys Glu Gln Glu Leu Ile Ala Lys Lys Thr Glu Lys Ala

435 440 445

Lys Tyr Leu Ser Leu Glu Thr Ile Lys Leu Ala Leu Glu Glu Phe Asn

450 455 460

Lys His Arg Asp Ile Asp Lys Gln Cys Arg Phe Glu Glu Ile Leu Ala

465 470 475 480

Asn Phe Ala Ala Ile Pro Met Ile Phe Asp Glu Ile Ala Gln Asn Lys

485 490 495

Asp Asn Leu Ala Gln Ile Ser Ile Lys Tyr Gln Asn Gln Gly Lys Lys

500 505 510

Asp Leu Leu Gln Ala Ser Ala Glu Asp Asp Val Lys Ala Ile Lys Asp

515 520 525

Leu Leu Asp Gln Thr Asn Asn Leu Leu His Lys Leu Lys Ile Phe His

530 535 540

Ile Ser Gln Ser Glu Asp Lys Ala Asn Ile Leu Asp Lys Asp Glu His

545 550 555 560

Phe Tyr Leu Val Phe Glu Glu Cys Tyr Phe Glu Leu Ala Asn Ile Val

565 570 575

Pro Leu Tyr Asn Lys Ile Arg Asn Tyr Ile Thr Gln Lys Pro Tyr Ser

580 585 590

Asp Glu Lys Phe Lys Leu Asn Phe Glu Asn Ser Thr Leu Ala Asn Gly

595 600 605

Trp Asp Lys Asn Lys Glu Pro Asp Asn Thr Ala Ile Leu Phe Ile Lys

610 615 620

Asp Asp Lys Tyr Tyr Leu Gly Val Met Asn Lys Lys Asn Asn Lys Ile

625 630 635 640

Phe Asp Asp Lys Ala Ile Lys Glu Asn Lys Gly Glu Gly Tyr Lys Lys

645 650 655

Ile Val Tyr Lys Leu Leu Pro Gly Ala Asn Lys Met Leu Pro Lys Val

660 665 670

Phe Phe Ser Ala Lys Ser Ile Lys Phe Tyr Asn Pro Ser Glu Asp Ile

675 680 685

Leu Arg Ile Arg Asn His Ser Thr His Thr Lys Asn Gly Ser Pro Gln

690 695 700

Lys Gly Tyr Glu Lys Phe Glu Phe Asn Ile Glu Asp Cys Arg Lys Phe

705 710 715 720

Ile Asp Phe Tyr Lys Gln Ser Ile Ser Lys His Pro Glu Trp Lys Asp

725 730 735

Phe Gly Phe Arg Phe Ser Asp Thr Gln Arg Tyr Asn Ser Ile Asp Glu

740 745 750

Phe Tyr Arg Glu Val Glu Asn Gln Gly Tyr Lys Leu Thr Phe Glu Asn

755 760 765

Ile Ser Glu Ser Tyr Ile Asp Ser Val Val Asn Gln Gly Lys Leu Tyr

770 775 780

Leu Phe Gln Ile Tyr Asn Lys Asp Phe Ser Ala Tyr Ser Lys Gly Arg

785 790 795 800

Pro Asn Leu His Thr Leu Tyr Trp Lys Ala Leu Phe Asp Glu Arg Asn

805 810 815

Leu Gln Asp Val Val Tyr Lys Leu Asn Gly Glu Ala Glu Leu Phe Tyr

820 825 830

Arg Lys Gln Ser Ile Pro Lys Lys Ile Thr His Pro Ala Lys Glu Ala

835 840 845

Ile Ala Asn Lys Asn Lys Asp Asn Pro Lys Lys Glu Ser Val Phe Glu

850 855 860

Tyr Asp Leu Ile Lys Asp Lys Arg Phe Thr Glu Asp Lys Phe Phe Phe

865 870 875 880

His Cys Pro Ile Thr Ile Asn Phe Lys Ser Ser Gly Ala Asn Lys Phe

885 890 895

Asn Asp Glu Ile Asn Leu Leu Leu Lys Glu Lys Ala Asn Asp Val His

900 905 910

Ile Leu Ser Ile Asp Arg Gly Glu Arg His Leu Ala Tyr Tyr Thr Leu

915 920 925

Val Asp Gly Lys Gly Asn Ile Ile Lys Gln Asp Thr Phe Asn Ile Ile

930 935 940

Gly Asn Asp Arg Met Lys Thr Asn Tyr His Asp Lys Leu Ala Ala Ile

945 950 955 960

Glu Lys Asp Arg Asp Ser Ala Arg Lys Asp Trp Lys Lys Ile Asn Asn

965 970 975

Ile Lys Glu Met Lys Glu Gly Tyr Leu Ser Gln Val Val His Glu Ile

980 985 990

Ala Lys Leu Val Ile Glu Tyr Asn Ala Ile Val Val Phe Glu Asp Leu

995 1000 1005

Asn Phe Gly Phe Lys Arg Gly Arg Phe Lys Val Glu Lys Gln Val

1010 1015 1020

Tyr Gln Lys Leu Glu Lys Met Leu Ile Glu Lys Leu Asn Tyr Leu

1025 1030 1035

Val Phe Lys Asp Asn Glu Phe Asp Lys Thr Gly Gly Val Leu Arg

1040 1045 1050

Ala Tyr Gln Leu Thr Ala Pro Phe Glu Thr Phe Lys Lys Met Gly

1055 1060 1065

Lys Gln Thr Gly Ile Ile Tyr Tyr Val Pro Ala Gly Phe Thr Ser

1070 1075 1080

Lys Ile Cys Pro Val Thr Gly Phe Val Asn Gln Leu Tyr Pro Lys

1085 1090 1095

Tyr Glu Ser Val Ser Lys Ser Gln Glu Phe Phe Ser Lys Phe Asp

1100 1105 1110

Lys Ile Cys Tyr Asn Leu Asp Lys Gly Tyr Phe Glu Phe Ser Phe

1115 1120 1125

Asp Tyr Lys Asn Phe Gly Asp Lys Ala Ala Lys Gly Lys Trp Thr

1130 1135 1140

Ile Ala Ser Phe Gly Ser Arg Leu Ile Asn Phe Arg Asn Ser Asp

1145 1150 1155

Lys Asn His Asn Trp Asp Thr Arg Glu Val Tyr Pro Thr Lys Glu

1160 1165 1170

Leu Glu Lys Leu Leu Lys Asp Tyr Ser Ile Glu Tyr Gly His Gly

1175 1180 1185

Glu Cys Ile Lys Ala Ala Ile Cys Gly Glu Ser Asp Lys Lys Phe

1190 1195 1200

Phe Ala Lys Leu Thr Ser Val Leu Asn Thr Ile Leu Gln Met Arg

1205 1210 1215

Asn Ser Lys Thr Gly Thr Glu Leu Asp Tyr Leu Ile Ser Pro Val

1220 1225 1230

Ala Asp Val Asn Gly Asn Phe Phe Asp Ser Arg Gln Ala Pro Lys

1235 1240 1245

Asn Met Pro Gln Asp Ala Asp Ala Asn Gly Ala Tyr His Ile Gly

1250 1255 1260

Leu Lys Gly Leu Met Leu Leu Gly Arg Ile Lys Asn Asn Gln Glu

1265 1270 1275

Gly Lys Lys Leu Asn Leu Val Ile Lys Asn Glu Glu Tyr Phe Glu

1280 1285 1290

Phe Val Gln Asn Arg Asn Asn

1295 1300

<210> 40

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 40

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Trp

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Pro Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 41

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 41

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Trp

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Pro Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 42

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 42

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Ala

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Pro Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 43

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 43

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Trp

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Tyr Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 44

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 44

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Ala

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Pro Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 45

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 45

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Trp

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Tyr Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 46

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 46

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Ala

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Tyr Asp Tyr Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 47

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 47

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Ala

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Phe Asp Tyr Asp Pro Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 48

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 48

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Tyr Ser Pro Cys Phe Ser Ala

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Asp Asp Pro Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 49

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 49

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Ala

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Phe Asp Tyr Asp Tyr Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555

<210> 50

<211> 1558

<212> PRT

<213> Artificial Sequence

<220>

<223> 合成的

<400> 50

Met Pro Lys Lys Lys Arg Lys Val Met Glu Ala Ser Pro Ala Ser Gly

1 5 10 15

Pro Arg His Leu Met Asp Pro His Ile Phe Thr Ser Asn Phe Asn Asn

20 25 30

Gly Ile Gly Arg His Lys Thr Tyr Leu Cys Tyr Glu Val Glu Arg Leu

35 40 45

Asp Asn Gly Thr Ser Val Lys Met Asp Gln His Arg Gly Phe Leu His

50 55 60

Asn Gln Ala Lys Asn Leu Leu Cys Gly Phe Tyr Gly Arg His Ala Glu

65 70 75 80

Leu Arg Phe Leu Asp Leu Val Pro Ser Leu Gln Leu Asp Pro Ala Gln

85 90 95

Ile Tyr Arg Val Thr Trp Phe Ile Ser Trp Ser Pro Cys Phe Ser Ala

100 105 110

Gly Cys Ala Gly Glu Val Arg Ala Phe Leu Gln Glu Asn Thr His Val

115 120 125

Arg Leu Arg Ile Phe Ala Ala Arg Ile Tyr Asp Asp Asp Tyr Leu Tyr

130 135 140

Lys Glu Ala Leu Gln Met Leu Arg Asp Ala Gly Ala Gln Val Ser Ile

145 150 155 160

Met Thr Tyr Asp Glu Phe Lys His Cys Trp Asp Thr Phe Val Asp His

165 170 175

Gln Gly Cys Pro Phe Gln Pro Trp Asp Gly Leu Asp Glu His Ser Gln

180 185 190

Ala Leu Ser Gly Arg Leu Arg Ala Ile Leu Gln Asn Gln Gly Asn Ser

195 200 205

Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Met

210 215 220

Ser Lys Leu Glu Lys Phe Thr Asn Cys Tyr Ser Leu Ser Lys Thr Leu

225 230 235 240

Arg Phe Lys Ala Ile Pro Val Gly Lys Thr Gln Glu Asn Ile Asp Asn

245 250 255

Lys Arg Leu Leu Val Glu Asp Glu Lys Arg Ala Glu Asp Tyr Lys Gly

260 265 270

Val Lys Lys Leu Leu Asp Arg Tyr Tyr Leu Ser Phe Ile Asn Asp Val

275 280 285

Leu His Ser Ile Lys Leu Lys Asn Leu Asn Asn Tyr Ile Ser Leu Phe

290 295 300

Arg Lys Lys Thr Arg Thr Glu Lys Glu Asn Lys Glu Leu Glu Asn Leu

305 310 315 320

Glu Ile Asn Leu Arg Lys Glu Ile Ala Lys Ala Phe Lys Gly Asn Glu

325 330 335

Gly Tyr Lys Ser Leu Phe Lys Lys Asp Ile Ile Glu Thr Ile Leu Pro

340 345 350

Glu Phe Leu Asp Asp Lys Asp Glu Ile Ala Leu Val Asn Ser Phe Asn

355 360 365

Gly Phe Thr Thr Ala Phe Thr Gly Phe Phe Asp Asn Arg Glu Asn Met

370 375 380

Phe Ser Glu Glu Ala Lys Ser Thr Ser Ile Ala Phe Arg Cys Ile Asn

385 390 395 400

Glu Asn Leu Thr Arg Tyr Ile Ser Asn Met Asp Ile Phe Glu Lys Val

405 410 415

Asp Ala Ile Phe Asp Lys His Glu Val Gln Glu Ile Lys Glu Lys Ile

420 425 430

Leu Asn Ser Asp Tyr Asp Val Glu Asp Phe Phe Glu Gly Glu Phe Phe

435 440 445

Asn Phe Val Leu Thr Gln Glu Gly Ile Asp Val Tyr Asn Ala Ile Ile

450 455 460

Gly Gly Phe Val Thr Glu Ser Gly Glu Lys Ile Lys Gly Leu Asn Glu

465 470 475 480

Tyr Ile Asn Leu Tyr Asn Gln Lys Thr Lys Gln Lys Leu Pro Lys Phe

485 490 495

Lys Pro Leu Tyr Lys Gln Val Leu Ser Asp Arg Glu Ser Leu Ser Phe

500 505 510

Tyr Gly Glu Gly Tyr Thr Ser Asp Glu Glu Val Leu Glu Val Phe Arg

515 520 525

Asn Thr Leu Asn Lys Asn Ser Glu Ile Phe Ser Ser Ile Lys Lys Leu

530 535 540

Glu Lys Leu Phe Lys Asn Phe Asp Glu Tyr Ser Ser Ala Gly Ile Phe

545 550 555 560

Val Lys Asn Gly Pro Ala Ile Ser Thr Ile Ser Lys Asp Ile Phe Gly

565 570 575

Glu Trp Asn Val Ile Arg Asp Lys Trp Asn Ala Glu Tyr Asp Asp Ile

580 585 590

His Leu Lys Lys Lys Ala Val Val Thr Glu Lys Tyr Glu Asp Asp Arg

595 600 605

Arg Lys Ser Phe Lys Lys Ile Gly Ser Phe Ser Leu Glu Gln Leu Gln

610 615 620

Glu Tyr Ala Asp Ala Asp Leu Ser Val Val Glu Lys Leu Lys Glu Ile

625 630 635 640

Ile Ile Gln Lys Val Asp Glu Ile Tyr Lys Val Tyr Gly Ser Ser Glu

645 650 655

Lys Leu Phe Asp Ala Asp Phe Val Leu Glu Lys Ser Leu Lys Lys Asn

660 665 670

Asp Ala Val Val Ala Ile Met Lys Asp Leu Leu Asp Ser Val Lys Ser

675 680 685

Phe Glu Asn Tyr Ile Lys Ala Phe Phe Gly Glu Gly Lys Glu Thr Asn

690 695 700

Arg Asp Glu Ser Phe Tyr Gly Asp Phe Val Leu Ala Tyr Asp Ile Leu

705 710 715 720

Leu Lys Val Asp His Ile Tyr Asp Ala Ile Arg Asn Tyr Val Thr Gln

725 730 735

Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Gln Asn Pro Gln

740 745 750

Phe Met Gly Gly Trp Asp Lys Asp Lys Glu Thr Asp Tyr Arg Ala Thr

755 760 765

Ile Leu Arg Tyr Gly Ser Lys Tyr Tyr Leu Ala Ile Met Asp Lys Lys

770 775 780

Tyr Ala Lys Cys Leu Gln Lys Ile Asp Lys Asp Asp Val Asn Gly Asn

785 790 795 800

Tyr Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu

805 810 815

Pro Lys Val Phe Phe Ser Lys Lys Trp Met Ala Tyr Tyr Asn Pro Ser

820 825 830

Glu Asp Ile Gln Lys Ile Tyr Lys Asn Gly Thr Phe Lys Lys Gly Asp

835 840 845

Met Phe Asn Leu Asn Asp Cys His Lys Leu Ile Asp Phe Phe Lys Asp

850 855 860

Ser Ile Ser Arg Tyr Pro Lys Trp Ser Asn Ala Tyr Asp Phe Asn Phe

865 870 875 880

Ser Glu Thr Glu Lys Tyr Lys Asp Ile Ala Gly Phe Tyr Arg Glu Val

885 890 895

Glu Glu Gln Gly Tyr Lys Val Ser Phe Glu Ser Ala Ser Lys Lys Glu

900 905 910

Val Asp Lys Leu Val Glu Glu Gly Lys Leu Tyr Met Phe Gln Ile Tyr

915 920 925

Asn Lys Asp Phe Ser Asp Lys Ser His Gly Thr Pro Asn Leu His Thr

930 935 940

Met Tyr Phe Lys Leu Leu Phe Asp Glu Asn Asn His Gly Gln Ile Arg

945 950 955 960

Leu Ser Gly Gly Ala Glu Leu Phe Met Arg Arg Ala Ser Leu Lys Lys

965 970 975

Glu Glu Leu Val Val His Pro Ala Asn Ser Pro Ile Ala Asn Lys Asn

980 985 990

Pro Asp Asn Pro Lys Lys Thr Thr Thr Leu Ser Tyr Asp Val Tyr Lys

995 1000 1005

Asp Lys Arg Phe Ser Glu Asp Gln Tyr Glu Leu His Ile Pro Ile

1010 1015 1020

Ala Ile Asn Lys Cys Pro Lys Asn Ile Phe Lys Ile Asn Thr Glu

1025 1030 1035

Val Arg Val Leu Leu Lys His Asp Asp Asn Pro Tyr Val Ile Gly

1040 1045 1050

Ile Ala Arg Gly Glu Arg Asn Leu Leu Tyr Ile Val Val Val Asp

1055 1060 1065

Gly Lys Gly Asn Ile Val Glu Gln Tyr Ser Leu Asn Glu Ile Ile

1070 1075 1080

Asn Asn Phe Asn Gly Ile Arg Ile Lys Thr Asp Tyr His Ser Leu

1085 1090 1095

Leu Asp Lys Lys Glu Lys Glu Arg Phe Glu Ala Arg Gln Asn Trp

1100 1105 1110

Thr Ser Ile Glu Asn Ile Lys Glu Leu Lys Ala Gly Tyr Ile Ser

1115 1120 1125

Gln Val Val His Lys Ile Cys Glu Leu Val Glu Lys Tyr Asp Ala

1130 1135 1140

Val Ile Ala Leu Ala Asp Leu Asn Ser Gly Phe Lys Asn Ser Arg

1145 1150 1155

Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys Met Leu

1160 1165 1170

Ile Asp Lys Leu Asn Tyr Met Val Asp Lys Lys Ser Asn Pro Cys

1175 1180 1185

Ala Thr Gly Gly Ala Leu Lys Gly Tyr Gln Ile Thr Asn Lys Phe

1190 1195 1200

Glu Ser Phe Lys Ser Met Ser Thr Gln Asn Gly Phe Ile Phe Tyr

1205 1210 1215

Ile Pro Ala Trp Leu Thr Ser Lys Ile Asp Pro Ser Thr Gly Phe

1220 1225 1230

Val Asn Leu Leu Lys Thr Lys Tyr Thr Ser Ile Ala Asp Ser Lys

1235 1240 1245

Lys Phe Ile Ser Ser Phe Asp Arg Ile Met Tyr Val Pro Glu Glu

1250 1255 1260

Asp Leu Phe Glu Phe Ala Leu Asp Tyr Lys Asn Phe Ser Arg Thr

1265 1270 1275

Asp Ala Asp Tyr Ile Lys Lys Trp Lys Leu Tyr Ser Tyr Gly Asn

1280 1285 1290

Arg Ile Arg Ile Phe Arg Asn Pro Lys Lys Asn Asn Val Phe Asp

1295 1300 1305

Trp Glu Glu Val Cys Leu Thr Ser Ala Tyr Lys Glu Leu Phe Asn

1310 1315 1320

Lys Tyr Gly Ile Asn Tyr Gln Gln Gly Asp Ile Arg Ala Leu Leu

1325 1330 1335

Cys Glu Gln Ser Asp Lys Ala Phe Tyr Ser Ser Phe Met Ala Leu

1340 1345 1350

Met Ser Leu Met Leu Gln Met Arg Asn Ser Ile Thr Gly Arg Thr

1355 1360 1365

Asp Val Ala Phe Leu Ile Ser Pro Val Lys Asn Ser Asp Gly Ile

1370 1375 1380

Phe Tyr Asp Ser Arg Asn Tyr Glu Ala Gln Glu Asn Ala Ile Leu

1385 1390 1395

Pro Lys Asn Ala Asp Ala Asn Gly Ala Tyr Asn Ile Ala Arg Lys

1400 1405 1410

Val Leu Trp Ala Ile Gly Gln Phe Lys Lys Ala Glu Asp Glu Lys

1415 1420 1425

Leu Asp Lys Val Lys Ile Ala Ile Ser Asn Lys Glu Trp Leu Glu

1430 1435 1440

Tyr Ala Gln Thr Ser Val Lys His Gly Ser Pro Lys Lys Lys Arg

1445 1450 1455

Lys Val Ser Gly Gly Ser Thr Asn Leu Ser Asp Ile Ile Glu Lys

1460 1465 1470

Glu Thr Gly Lys Gln Leu Val Ile Gln Glu Ser Ile Leu Met Leu

1475 1480 1485

Pro Glu Glu Val Glu Glu Val Ile Gly Asn Lys Pro Glu Ser Asp

1490 1495 1500

Ile Leu Val His Thr Ala Tyr Asp Glu Ser Thr Asp Glu Asn Val

1505 1510 1515

Met Leu Leu Thr Ser Asp Ala Pro Glu Tyr Lys Pro Trp Ala Leu

1520 1525 1530

Val Ile Gln Asp Ser Asn Gly Glu Asn Lys Ile Lys Met Leu Ser

1535 1540 1545

Gly Gly Ser Pro Lys Lys Lys Arg Lys Val

1550 1555