CN106715474A - 稳定化的流感血凝素茎区三聚体及其用途 - Google Patents

稳定化的流感血凝素茎区三聚体及其用途 Download PDF

Info

Publication number
CN106715474A
CN106715474A CN201580041202.3A CN201580041202A CN106715474A CN 106715474 A CN106715474 A CN 106715474A CN 201580041202 A CN201580041202 A CN 201580041202A CN 106715474 A CN106715474 A CN 106715474A
Authority
CN
China
Prior art keywords
seq
amino acid
sequence
influenza
protein
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201580041202.3A
Other languages
English (en)
Other versions
CN106715474B (zh
Inventor
J.R.马斯科拉
J.C.博英顿
H.M.亚辛
P.D.邝
B.S.格拉哈姆
M.凯恩基约
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
US OF AMERICA AS REPRESENTED B
US Department of Health and Human Services
Original Assignee
US OF AMERICA AS REPRESENTED B
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by US OF AMERICA AS REPRESENTED B filed Critical US OF AMERICA AS REPRESENTED B
Priority to CN202110772479.0A priority Critical patent/CN114014937A/zh
Publication of CN106715474A publication Critical patent/CN106715474A/zh
Application granted granted Critical
Publication of CN106715474B publication Critical patent/CN106715474B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/145—Orthomyxoviridae, e.g. influenza virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16111—Influenzavirus A, i.e. influenza A virus
    • C12N2760/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16111—Influenzavirus A, i.e. influenza A virus
    • C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Toxicology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

引发广泛保护性抗流感抗体的疫苗。一些疫苗包含在其表面上展示来自流感病毒的HA三聚体的纳米颗粒。纳米颗粒是包含连接到流感HA蛋白的茎区的单体亚基(例如，铁蛋白)的融合蛋白。融合蛋白自组装以形成HA‑展示纳米颗粒。疫苗仅包含连接到三聚化结构域的流感HA蛋白的茎区。还提供了融合蛋白和编码此类蛋白的核酸分子，以及使用本发明的纳米颗粒检测抗流感抗体的测定法。

Description

稳定化的流感血凝素茎区三聚体及其用途
发明概述
本发明提供了新的基于血凝素(HA)蛋白的流感疫苗，其是易于制造的，有力的并且引发针对流感HA蛋白的茎区的广泛中和性流感抗体。特别地，本发明提供了融合前构象的修饰的流感HA茎区蛋白及其部分，其可用于诱导中和性抗体的产生。本发明还提供在其表面上表达流感HA蛋白的新型基于纳米颗粒(np)的疫苗。此类纳米颗粒包含融合蛋白，每个融合蛋白包含连接到来自流感HA蛋白的茎区的抗原性或免疫原性部分的铁蛋白的单体亚基。因为此类纳米颗粒在其表面上展示流感HA蛋白茎区，所以它们可以用于针对流感病毒对个体接种疫苗。
发明背景
通过针对流感病毒接种疫苗诱导的保护性免疫应答主要针对病毒HA蛋白，其是病毒表面上负责病毒与宿主细胞受体的相互作用的糖蛋白。病毒表面上的HA蛋白是HA蛋白单体的三聚体，其被酶促切割以产生氨基端末端HA1和羧基端末端HA2多肽。球状头部仅由HA1多肽的主要部分组成，而将HA蛋白锚定到病毒脂质包膜中的茎由HA2和HA1的部分组成。HA蛋白的球状头部包括两个结构域：受体结合结构域(RBD)，包括唾液酸结合位点的约148个氨基酸残基结构域，和退化酯酶结构域(vestigial esterase domain)，刚好低于RBD的较小的约75个氨基酸残基区域。球状头部牵涉几个包括免疫显性表位的抗原位点。实例包括Sa，Sb，Ca1，Ca2和Cb抗原位点(参见例如Caton AJ et al,1982,Cell 31,417-427)。RBD-A区包括Sa抗原位点和Sb抗原位点的部分。
针对流感的抗体通常靶向HA球状头中的可变抗原位点，其围绕保守的唾液酸结合位点，因此仅中和抗原紧密相关的病毒。HA头部的可变性是由于流感病毒的恒定抗原漂移所致，并且造成流感的季节性流行病。相比之下，HA茎是高度保守的，并且经历很少的抗原漂移。不幸的是，不同于免疫显性头部，保守的HA茎不是非常免疫原性的。此外，病毒基因组的基因区段可以在宿主物种中进行重配(抗原漂移)，创建具有改变的抗原性的能够变成大流行的新病毒[Salomon,R.et al.Cell 136,402-410(2009)]。直到现在，每年更新流感疫苗以反映即将到来的流行病毒的预测的HA和神经氨酸酶(NA)。
最近，分离了一类全新的针对流感病毒的广泛中和性抗体，其识别高度保守的HA茎[Corti,D.et al.J Clin Invest 120,1663-1673(2010)；Ekiert,D.C.et al.Science324,246-251(2009)；Kashyap,A.K.et al.Proc Natl Acad Sci USA105,5986-5991(2008)；Okuno,Y.et al.J Virol 67,2552-2558(1993)；Sui,J.et al.Nat Struct MolBiol 16,265-273(2009)；Ekiert,D.C.et al.Science 333,843-850(2011)；Corti,D.etal.Science 333,850-856(2011)]。与毒株特异性抗体不同，那些抗体能够中和多种抗原性独特的病毒，因此诱导此类抗体已成为下一代通用疫苗开发的焦点[Nabel,G.J.et al.NatMed 16,1389-1391(2010)]。然而，通过疫苗接种用此类异源中和概况强力引发这些抗体是困难的[Steel,J.et al.MBio 1,e0018(2010)；Wang,T.T.et al.PLoS Pathog 6,e1000796(2010)；Wei,C.J.et al.Science 329,1060-1064(2010)]。通过遗传操作除去HA(其含有竞争性表位)的免疫显性头部区和稳定化所得茎结构域是改善这些广泛中和性茎抗体的引发的一种潜在方式。
目前用于流感的疫苗策略使用化学灭活或减毒活流感病毒。两种疫苗通常在含胚卵中产生，其由于耗时的方法和有限的生产能力而存在主要的制造限制。当前疫苗的另一个更关键的限制是其高度毒株特异性功效。在2009年H1N1大流行的出现期间，这些挑战变得显著，从而验证了能够克服这些限制的新疫苗平台的必要性。病毒样颗粒代表了这种替代方法之一，目前正在临床试验中进行评估[Roldao,A.et al.Expert Rev Vaccines 9,1149-1176(2010)；Sheridan,C.Nat Biotechnol 27,489-491(2009)]。代替含胚卵，通常包含HA，NA和基质蛋白1(M1)的VLP可以在哺乳动物或昆虫细胞表达系统中大规模生产[Haynes,J.R.Expert Rev Vaccines 8,435-445(2009)]。这种方法的优点是其颗粒，多价性质和正确折叠、三聚体HA刺突的真实展示，其忠实模拟感染性病毒体。相比之下，由于其组装的性质，有包膜的VLP含有小的但有限的宿主细胞组分，其可以在重复使用该平台后呈现潜在的安全性，免疫原性挑战[Wu,C.Y.et al.PLoS One 5,e9784(2010)]。此外，VLP诱导的免疫与当前疫苗基本相同，因此不可能显著改善疫苗诱导的保护性免疫的效力和广度。除了VLP外，重组HA蛋白也已经在人体中进行了评估[Treanor,J.J.et al.Vaccine 19,1732-1737(2001)；Treanor,J.J.JAMA 297,1577-1582(2007)]，尽管诱导保护性中和性抗体滴度的能力有限。在这些试验中使用的重组HA蛋白在昆虫细胞中产生并且可能不优先形成天然三聚体[Stevens,J.Science303,1866-1870(2004)]。
尽管常规流感疫苗有几种替代，但在过去几十年中生物技术的进步已经允许利用生物材料的工程化来产生新的疫苗平台。铁蛋白，几乎所有活生物体中发现的铁贮存蛋白，是已经广泛研究和工程化以用于许多潜在的生物化学/生物医学目的的实例[Iwahori,K.U.S.Patent 2009/0233377(2009)；Meldrum,F.C.et al.Science 257,522-523(1992)；Naitou,M.et al.U.S.Patent2011/0038025(2011)；Yamashita,I.Biochim Biophys Acta1800,846-857(2010)]，包括用于展示外源表位肽的潜在疫苗平台[Carter,D.C.etal.U.S.Patent 2006/0251679(2006)；Li,C.Q.et al.Industrial Biotechnol 2,143-147(2006)]。其作为疫苗平台的用途是特别有趣的，这是由于其自身组装和抗原的多价呈递，这比单价形式诱导更强的B细胞应答以及诱导T细胞非依赖性抗体应答[Bachmann,M.F.etal.Annu Rev Immunol 15,235-270(1997)；Dintzis,H.M.et al.Proc Natl Acad Sci USA73,3671-3675(1976)]。此外，铁蛋白的分子结构，其由组装成具有432对称的八面体笼的24个亚基组成，具有在其表面上展示多聚体抗原的潜力。
仍然需要提供强力的针对流感病毒的保护的有效的流感疫苗。特别地，仍然需要保护个体免受流感病毒异源株，包括进化中的未来的季节性和大流行性流感病毒株的流感疫苗。本发明通过提供新颖的基于纳米颗粒的疫苗来满足这种需要，所述疫苗由新的HA稳定化的茎(SS)组成，没有遗传上融合到纳米颗粒表面的可变免疫显性头部区(gen6HA-SSnp)，从而产生流感疫苗，其是易于制造的，有力的，并且引发广泛异亚型保护性的抗体。
附图简述
图1a显示了HA头部的基于结构的除去允许保留茎免疫原抗原性。带状模型描绘了HA-SS设计途径，开始于融合到T4折叠物(foldon)三聚化结构域(在HA胞外域下方为绿色)的HA胞外域的模型。最后三个HA-SS设计(Gen4-6)遗传融合到铁蛋白纳米颗粒(下图)。每个HA三聚体的一个单体被遮蔽。用于创建Gen6的核心稳定化突变显示为球体。每种HA-SS免疫原设计下方显示了三聚化百分比(包括折叠物)和对规定mAb的抗原亲和常数(KD，M)。ND，未确定；NA，不适用。图1b分别显示没有折叠物结构域的H1N1HA胞外域(PDB ID 1GBN)，Gen4HA-SS和Gen6HA-SS的HA部分的表面呈现，其通过与H5N1 2004VN的序列保守加阴影(深灰色，可变；白色，保守)。分别对于Gen4和Gen6HA-SS，无折叠物结构域的免疫原的HA茎百分比增加。*进一步评估此免疫原，并且在本公开的实施例部分中称为H1-SS-np。图1c显示了描绘在Gen6HA-SS中Glu103-Lys51盐桥替换为Leu103-Met51疏水对的横截面图的带状图。虚线(左)指示横截面的位置。图1d显示了以其可溶性和纳米颗粒形式呈现的Gen6HA-SS的抗原性。三个图显示了一个头(CH65)和三个茎特异性抗体(CR6261，CR9114，FI6v3)对Gen6’HA-SS(左图)，H1-SS-np(中图)和H1-SS-np’(右图)的ELISA结合。浓度范围为10-6.40×10-4μg/mL的抗体的ELISA结合。图1e和图1f显示了H1-SS-np(图1e)和H1-SS-np’(图1f)与HA茎定向性bNAb结合的Octet传感图。将H1-SS-np固定在Octet探针上，并与不同浓度的抗体结合片段Fab或scFv茎定向性抗体温育，其在每个传感图的顶部指示。图1g显示通过抗IgM(＝总受体活性)，空np，HA-np(HA含有Y98F突变，以消除与唾液酸的非特异性结合)和H1-SS-np’的野生型IGHV1-69v-基因逆转的CR6261BCR(左图)对双重Ile53Ala/Phe54Ala CDRH2突变体BCR(右图)的刺激通过流式细胞术测量为Ca2+敏感染料FuraRed的Ca2+结合/未结合状态的比率。
图2a显示三聚体，而不是纳米颗粒茎免疫原，展示HA茎展开。左图描述了Gen3HA-SS(黑色和灰色)和mAb C179(标记)之间的复合物的晶体结构的带状图。图2a的中间图示出了在两个不同视图(侧面和底部)中比较晶体结构(光)与模型(暗)的展开的草图。图2a的右图显示了Gen3HA-SS/C179结合界面与1957H2N2HA/C179结合界面(PDB ID 4HLZ)的重叠。抗体CDR环对于重链用“H”标记，对于轻链用“L”标记。重链框架3环标记为FR3。RMSD，均方根偏差。图2b描绘了与图2a中相同的图格式，显示了Gen4HA-SS，并且在右图中，Gen4HA-SS/CR6261重链结合界面与1918H1N1HA/CR6261结合界面(PDB ID 3GBN)的重叠。图2c显示H1-SS-np冷冻电子显微术(cryo-electron microscopy)分析。前两个图分别显示了Gen4HA-SS晶体结构(剪切(cropped))和H1-SS-np模型，分别适合于一个H1-SS-np刺突的冷冻电子显微术图。图2c的接下来两个图显示了适合到H1-SS-np低温电子显微术图中的整个H1-SS-np模型的两个不同视图。图2d显示分别用Superdex 20010/300和Superose 610/300柱得到的HA，Gen4HA-SS和H1-SS-np’(左图)和HA np，Gen4HA-SS-np np和H1-SS-np’和H1-SS-np(右图)的大小排阻层析中流感病毒HA和HA-SS不溶性和纳米颗粒形式的表征。图2e是HA-np(左图)和Gen4HA-SS-np(中图)和H1-SS-np(右图)的负染色透射电子显微术图像。最初以67,000×放大率记录图像。图2f显示H1-SS-np场的低温EM图像。箭头描绘一些环样纳米颗粒；比例尺为20nm。图2g显示了通过纳米颗粒(插图)的全局圆形平均值的2D径向密度概况(曲线)对H1-SS-np的大小分析。该概况示出了两层结构，其具有以距离颗粒中心约为中心的基峰和跨越约至范围的第二峰。峰高度的差异对于以含有几个离散刺突的层为顶部的更连续的蛋白质层是一致的。图2h显示H1-SS-np的无参考的2D类平均值，没有施加对称。类别指示具有蛋白质壳和突出的刺突密度的颗粒的不同视图，并且视图与预期的八面体对称一致。图2i通过傅里叶壳关联(FSC)图的H1-SS-np 3D重建的分辨率评估。遵循如在RELION软件包中实施的金标准程序(gold-standard procedure)，使用FSC(0.143)作为截留值。
图3a显示免疫的小鼠和雪貂的免疫应答。左图显示针对多种多样的HA蛋白的抗体端点滴度，并且右图显示来自用SAS佐剂化(SAS-adjuvanted)的H1-SS-np免疫的小鼠(每组n＝10)的血清的中和滴度。图3b显示了用SAS-佐剂化的空np(n＝5)，H1-SS-np’(n＝6)，2006-07TIV(n＝6)或H5HA(2xDNA/1xMIV；n＝6)免疫的雪貂的免疫应答。图3b的左图显示了H1-SS-np’免疫血清对多种多样的HA蛋白的抗体端点滴度，并且右图显示了来自四种免疫方案的血清的HA茎反应性。图3c显示了用三种施用方案免疫的雪貂的血清的中和滴度。在加强后两周对每个个体动物显示抗体端点和IC50滴度。虚线指示ELISA和假型化慢病毒报告物测定法两者的基线(1:25稀释)。误差棒表示平均值±s.d。使用双尾学生t检验(two-tailed student’s t-test)进行统计分析。
图4a显示了在小鼠和雪貂中针对致死性H5N1 2004VN流感病毒攻击赋予的免疫保护。在第0、8和11周，用SAS-佐剂化的空np或H1-SS-np对BALB/c小鼠(每组n＝10)接种疫苗三次，或保持未接种疫苗(未处理)。最后一次疫苗接种后四周，用高剂量(25LD50)的H5N12004VN病毒攻击小鼠，并监测体重减轻(左图)和存活(右图)达14天。图4b显示用SAS-佐剂化的空np(n＝5)，H1-SS-np’(n＝6)，2006-07TIV(n＝6)或H5HA(DNA/MIV；n＝6)，并在用1000TCID50的H5N1 2004VN最后免疫后6周攻击。监测体重减轻(左图)和存活(右图)达14天。图4c显示在用高剂量(25LD50)的H5N1 2004VN流感病毒攻击之前24小时用来自未处理或H1-SS-np-免疫动物的10mg Ig被动免疫(腹膜内)的BALB/c小鼠(每组n＝10)。监测体重减轻(左图)和存活(右图)达14天。在图4a，4b和4c的每一个中，黑色虚线(右图)指示50％存活。使用时序(Mantel-Cox)检验进行统计分析。图4d显示了未处理和H1-SS-np免疫Ig的表征。通过ELISA，未处理Ig(左)和H1-SS-np-免疫Ig(右)对空铁蛋白np和各种HA蛋白的结合。图4e显示在输注多克隆Ig后24小时的小鼠血清中Gen6HA-SS特异性Ig的估计浓度。
图5-24提供了用于产生本发明的肽构建体的质粒图谱和序列。如本公开表2中详细描述的，图5显示了包含SEQ ID NO:266的Gen6_H1NC99_K394M/E446L/E448Q/R449W/D452L/Y437D/N438L_N19Q的图谱。图6显示了包含SEQ ID NO:273的Gen6_H1CA09_K394M/E446L/E448Q/R449W/D452L/Y437D/N438L_N19Q的图谱。图7显示包含SEQ ID NO:280的Gen6_H2Sing57_K394M/M445L/E446L/E448Q/R449W/D452L/Y437D/N438L_N19Q的图谱。图8显示包含SEQ ID NO:287的Gen6_H5Ind05K394M/M445L/E446L/E448Q/R449W/D452L/Y437D/N438L/S49bW_N19Q的图谱。图9显示包含SEQ ID NO:294的Gen6_H1NC99_K394M/E446L_N19Q的图谱。图10显示包含SEQ ID NO:301的Gen6_H1NC99_K394M/E446L/Y437D/N438L_N19Q的图谱。图11显示包含SEQ ID NO:308的Gen6_H1NC99_K394I/E446I/Y437D/N438L_N19Q的图谱。图12显示包含SEQ ID NO:315的Gen6H1NC99K394L/E446I/Y437D/N438L_N19Q的图谱。图13显示包含SEQ ID NO:322的Gen6_H1NC99_K394L/E446L/Y437D/N438L_N19Q的图谱。图14显示包含SEQ ID NO:329的Gen6_H1NC99_K394M/E446M/Y437D/N438L_N19Q的图谱。图15显示包含SEQ ID NO:336的Gen6H1NC99K394Q/E446Q/Y437D/N438L_N19Q的图谱。图16显示包含SEQ ID NO:343的Gen6H1NC99K394M/E446L/Y437D/N438L/H45N/V47T_N19Q的图谱。图17显示包含SEQ ID NO:350的Gen6H1NC99V36I/K394M/L445M/E446L/E448Q/R449F/D452L/Y437D/N438L N19Q的图谱。图18显示包含SEQ ID NO:357的Gen6_H1NC99_K394M/E446L/E448Q/R449W/D452L/S402aN/G402cT/S402dG/T402fA/Y437D/N438L_N19Q的图谱。图19显示包含SEQ ID NO:364的Gen6_H1NC99_K394M/E446L/E448Q/R449W/D452L/S402bG/G402cN/S402eT/T402fA/Y437D/N438L_N19Q的图谱。图20显示包含SEQ ID NO:371的Gen6_H1NC99_K394M/E446L/E448Q/R449W/D452L/S402eN/Y437D/N438L_N19Q的图谱。图21显示了包含SEQID NO:378的Gen6H1NC99K394M/E446L/E448Q/R449W/D452L/G402cN/G402eT/T402fA/Q370N/E372T/Y437D/N438L_S21T的图谱。图22显示了包含SEQ ID NO:386的Gen6_H1NC99_K394M/E446L/E448Q/R449W/D452L/G402cN/G402eT/T402fA/Q370N/E372T/Y437D/N438L_S21T/Q69N的图。图23显示了包含SEQ ID NO:392的Gen6_H1NC99_K394M/E446L/Y437D/N438L/Δ172-174的图。图24显示了包含SEQ ID NO:399的Gen6_H1NC99_rpk3_Dloop2的图。
发明详述
本发明涉及用于流感病毒的新型疫苗。更具体地，本发明涉及新的基于流感HA蛋白的疫苗，其引发针对来自一大批流感病毒的HA蛋白的茎区的免疫应答。它还涉及自组装纳米颗粒，所述自组装纳米颗粒在其表面上展示来自流感HA蛋白的茎区的融合前构象的免疫原性部分。此类纳米颗粒可用于针对流感病毒对个体接种疫苗。因此，本发明还涉及用于产生此类纳米颗粒的蛋白质构建体和编码此类蛋白质的核酸分子。另外，本发明涉及生产本发明的纳米颗粒的方法，以及使用此类纳米颗粒对个体接种疫苗的方法。
在进一步描述本发明前，应当理解本发明不限于描述的具体实施方案，因此当然可以有所变化。还应当理解，本文中使用的术语仅为了描述具体的实施方案，而并不意图为限制性的，因为本发明的范围仅会以权利要求书为限。
应当注意到，如本文中及所附权利要求书中使用的，单数形式“一个”、“一种”和“该/所述”包括复数提及物，除非上下文另有明确规定。例如，核酸分子指一种或多种核酸分子。因此，术语“一个”、“一种”、“一个/种或多个/种”和“至少一个/种”可以互换使用。类似地，术语“包含”、“包括”和“具有”可以互换使用。进一步注意到，权利要求书可以撰写为排除任何任选要素。因此，此陈述意图充当与权利要求要素的叙述结合使用排除术语，如“单独”、“仅”等，或者使用“负”限定的前置基础。
在上文外，除非另有明确定义，本文中公开的各个实施方案共同的下列术语和短语如下定义：
如本文中使用的，蛋白质构建体是由人工制备的蛋白质，其中两个或更多个氨基酸序列以自然界中未发现的方式共价连接。被连接的氨基酸序列可以是相关的或不相关的。如本文所使用的，如果通常没有发现多肽序列的氨基酸序列在其天然环境(例如细胞内)中通过共价键连接在一起，则它们是不相关的。例如，通常没有发现构成铁蛋白的单体亚基的氨基酸序列和流感HA蛋白的氨基酸序列通过共价键连接在一起。因此，此类序列被认为是不相关的。
蛋白质构建体还可以包含相关的氨基酸序列。例如，流感HA蛋白的结构使得头部区氨基酸序列在两端侧翼为茎区氨基酸序列。通过遗传手段，可以通过从头部区的中间除去氨基酸残基，同时保持侧翼为茎区序列的头部区的部分，来创建HA蛋白的缺失形式。虽然最终分子中序列的顺序保持相同，但氨基酸之间的空间关系将不同于天然蛋白。因此，此类分子将被认为是蛋白质构建体。根据本发明，蛋白质构建体也可以称为融合蛋白。
蛋白质构建体中的氨基酸序列可以彼此直接连接，或者它们可以使用接头序列连接。接头序列，肽或多肽是用于连接具有期望特征(例如，结构，表位，免疫原性，活性等)的两种蛋白质的短(例如，2-20)氨基酸序列。接头序列通常不具有其自身的活性，并且通常用于允许蛋白质构建体的其它部分呈现期望的构象。接头序列通常由小氨基酸残基和/或其运行(runs)，例如丝氨酸，丙氨酸和甘氨酸制备，尽管不排除使用其它氨基酸残基。
如本文中使用的，术语免疫原性是指特定蛋白质或其特定区域引发对特定蛋白质或包含与特定蛋白质具有高度同一性的氨基酸序列的蛋白质的免疫应答的能力。根据本发明，具有高同一性程度的两种蛋白质具有至少80％相同，至少85％相同，至少87％相同，至少90％相同，至少92％相同，至少93％相同，至少94％相同，至少95％相同，至少96％相同，至少97％相同，至少98％相同或至少99％相同的氨基酸序列。测定两个氨基酸或核酸序列之间的百分比同一性的方法是本领域已知的。
如本文中使用的，对本发明的疫苗或纳米颗粒的免疫应答是受试者中形成对疫苗中存在的HA蛋白的体液和/或细胞免疫应答。为了本发明的目的，“体液免疫应答”是指由抗体分子(包括分泌型(IgA)或IgG分子)介导的免疫应答，而“细胞免疫应答”是由T淋巴细胞和/或其它白血细胞介导的。细胞免疫的一个重要方面涉及溶细胞性T细胞(“CTL”)的抗原特异性应答。CTL对肽抗原具有特异性，所述肽抗原与由主要组织相容性复合物(MHC)编码并且在细胞表面上表达的蛋白质联合呈现。CTL有助于诱导和促进细胞内微生物的破坏或被此类微生物感染的细胞的溶解。细胞免疫的另一方面涉及辅助T细胞的抗原特异性应答。辅助T细胞作用为帮助刺激非特异性效应细胞针对细胞的功能，并且聚焦非特异性效应细胞针对细胞的活性，所述细胞在其表面上展示与MHC分子联合的肽抗原。细胞免疫应答还指由活化的T细胞和/或其它白细胞(包括源自CD4+和CD8+T细胞的那些)产生的细胞因子，趋化因子和其它此类分子的产生。
因此，免疫应答可以是刺激CTL和/或辅助T细胞的产生或激活的应答。也可以刺激趋化因子和/或细胞因子的产生。疫苗还可以引发抗体介导的免疫应答。因此，免疫应答可以包括一种或多种以下效应：由B细胞产生抗体(例如IgA或IgG)；和/或特异性针对存在于疫苗中的HA蛋白的抑制物(suppressor)，细胞毒性或辅助T细胞和/或T细胞的活化。这些应答可用来中和感染性(例如抗体依赖性保护)，和/或介导抗体-补体或抗体依赖性细胞细胞毒性(ADCC)以向免疫的个体提供保护。此类反应可以使用本领域熟知的标准免疫测定法和中和测定法来测定。
如本文中使用的，术语抗原性的，抗原性等是指由抗体或一组抗体结合的蛋白质。类似地，蛋白质的抗原部分是被抗体或一组抗体识别的任何部分。根据本发明，通过抗体识别蛋白质是指抗体选择性地与蛋白质结合。如本文中使用的，短语选择性地结合，选择性结合等是指抗体与同HA无关的结合蛋白或样品或测定法中非蛋白质组分形成对比优先结合HA蛋白的能力。优先结合HA的抗体是结合HA但不显著结合可能存在于样品或测定法中的其它分子或组分的抗体。认为显著的结合是例如抗HA抗体与非HA分子的结合，其亲和力或亲合力大到足以干扰测定法检测和/或测定样品中抗流感抗体，或HA蛋白水平的能力。可存在于样品或测定法中的其它分子和化合物的实例包括但不限于非HA蛋白，如白蛋白，脂质和碳水化合物。根据本发明，非HA蛋白是具有与本文公开的流感HA蛋白的序列共享小于60％同一性的氨基酸序列的蛋白质。在一些实施方案中，一种或多种抗体提供广泛的异亚型保护。在一些实施方案中，一种或多种抗体是中和性的。
如本文中使用的，中和性抗体是防止流感病毒完成一轮复制的抗体。如本文所定义的，一轮复制指病毒的生命周期，从病毒附着到宿主细胞开始，并以从宿主细胞出芽新形成的病毒结束。该生命周期包括但不限于以下步骤：附着于细胞，进入细胞，HA蛋白的切割和重排，病毒膜与内体膜的融合，病毒核糖核蛋白向细胞质的释放，形成新病毒颗粒和自宿主细胞膜的病毒颗粒的出芽。根据本发明，中和性抗体是抑制一个或多个此类步骤的抗体。
如本文中使用的，广泛中和性抗体是中和流感病毒的多于一种类型，亚型和/或毒株的抗体。例如，针对来自A型流感病毒的HA蛋白引发的广泛中和性抗体可以中和B型或C型病毒。作为另一个实例，针对来自I型流感病毒的HA蛋白引发的广泛中和性抗体可以中和组2病毒。作为另一个实例，针对来自病毒的一种亚型或株的HA蛋白引发的广泛中和性抗体可以中和病毒的另一种亚型或株。例如，针对来自H1流感病毒的HA蛋白引发的广泛中和性抗体可以中和来自一种或多种选自下组的亚型的病毒：H2,H3,H4,H5,H6,H7,H8,H8,H10,H11,H12,H13,H14,H15,H16,H17或H18。
根据本发明，用于分类流感病毒的所有命名法是本领域技术人员通常使用的。因此，流感病毒的类型或组是指A型流感，B型流感或C型流感。本领域技术人员应当理解，病毒作为特定类型的命名涉及在各自的M1(基质)蛋白质或NP(核蛋白)中的序列差异。A型流感病毒进一步分为组1和组2。这些组进一步分为亚型，其指基于其HA蛋白的序列的病毒分类。目前普遍认可的亚型的实例是H1,H2,H3,H4,H5,H6,H7,H8,H8,H10,H11,H12,H13,H14,H15,H16,H17或H18。组1流感亚型是H1,H2,H5,H6,H8,H9,H11,H12,H13,H16,H17和H18。组2流感亚型是H3,H4,H7,H10,H14,和H15。最后，术语毒株是指亚型内彼此不同之处在于它们在其基因组中具有小的遗传变异的病毒。
如本文中使用的，流感血凝素蛋白或HA蛋白是指全长流感血凝素蛋白或其任何部分，其可用于产生本发明的蛋白质构建体和纳米颗粒或能够引发免疫应答。优选的HA蛋白是能够形成三聚体的那些。全长流感HA蛋白的表位是指此类蛋白质的部分，其可以引发针对同源流感病毒株，即衍生HA的菌株的抗体应答。在一些实施方案中，此类表位也可以引发针对异源流感病毒株，即具有与免疫原的HA不同的HA的毒株的抗体应答。在一些实施方案中，表位引发广泛异亚型保护性应答。在一些实施方案中，表位引发中和性抗体。
如本文中使用的，变体指在序列上与参照序列相似但不相同的蛋白质或核酸分子，其中变体蛋白质(或由变体核酸分子编码的蛋白质)的活性没有显著改变。这些序列变异可以是天然存在的变异或者它们可以经由使用本领域技术人员已知的遗传工程化技术来工程化改造。此类技术的例子可见Sambrook J,Fritsch E F,Maniatis T等,于Molecular Cloning--A Laboratory Manual,2nd Edition,Cold Spring HarborLaboratory Press,1989,pp.9.31-9.57)，或于Current Protocols in MolecularBiology,John Wiley&Sons,N.Y.(1989),6.3.1-6.3.6，这两篇的完整内容通过提及并入本文。
就变体而言，氨基酸或核酸序列的任何类型变化是可允许的，只要所得的变体蛋白质保留引发针对流感病毒的中和性或非中和性抗体的能力。此类变异的例子包括但不限于缺失、插入、取代及其组合。例如，就蛋白质而言，本领域技术人员公知的是，一个或多个(例如2,3,4,5,6,7,8,9或10)氨基酸经常可以从蛋白质的氨基和/或羧基端末端除去，而不显著影响所述蛋白质的活性。类似地，一个或多个(例如2,3,4,5,6,7,8,9或10)氨基酸经常可以插入蛋白质中，而不显著影响蛋白质的活性。在已经进行插入的变体中，插入的氨基酸可以通过参考其后进行插入的氨基酸残基来提及。例如，在氨基酸残基402之后插入四个氨基酸残基可以称为402a-402d。此外，如果那些插入的氨基酸之一随后被另一个氨基酸取代，则这种变化可以参考字母位置提及。例如，用苏氨酸取代插入的甘氨酸(在插入物的另一个位置中)可以称为S402dT。
如记录的，相对于本文中公开的流感HA蛋白，本发明的变体蛋白质可以含有氨基酸取代。任何氨基酸取代是可允许的，只要蛋白质的活性不受显著影响。在这点上，本领域中应当理解，氨基酸可以基于其物理特性而分成组。此类组的例子包括但不限于带电荷的氨基酸、不带电荷的氨基酸、极性不带电荷的氨基酸、和疏水性氨基酸。含有取代的优选变体是那些其中的氨基酸用来自相同组的氨基酸取代的变体。此类取代称为保守取代。
天然存在的残基可以基于共同的侧链特性而分成类：
1)疏水性：Met,Ala,Val,Leu,Ile；
2)中性亲水性：Cys,Ser,Thr；
3)酸性：Asp,Glu；
4)碱性：Asn,Gln,His,Lys,Arg；
5)影响链取向的残基：Gly,Pro；和
6)芳香基：Trp,Tyr,Phe。
例如，非保守取代可以牵涉用这些类别之一的成员替换来自另一类别的成员。
在进行氨基酸变化中，可以考虑氨基酸的亲水指数。基于每种氨基酸的疏水性和电荷性质，已给每种氨基酸的亲水指数赋值。亲水指数是：异亮氨酸(+4.5)；缬氨酸(+4.2)；亮氨酸(+3.8)；苯丙氨酸(+2.8)；半胱氨酸/胱氨酸(+2.5)；甲硫氨酸(+1.9)；丙氨酸(+1.8)；甘氨酸(-0.4)；苏氨酸(-0.7)；丝氨酸(-0.8)；色氨酸(-0.9)；酪氨酸(-1.3)；脯氨酸(-1.6)；组氨酸(-3.2)；谷氨酸(-3.5)；谷氨酰胺(-3.5)；天冬氨酸(-3.5)；天冬酰胺(-3.5)；赖氨酸(-3.9)；和精氨酸(-4.5)。本领域一般了解亲水氨基酸指数在赋予蛋白质相互作用性生物学功能中的重要性(Kyte等,1982,J.Mol.Biol.157:105-31)。已知可以用某些氨基酸替代其它具有相似亲水指数或分值的氨基酸，而仍然保留相似的生物学活性。在进行基于亲水指数的变化中，亲水指数在±2之内的氨基酸取代是优选的，在±1之内的那些氨基酸取代是特别优选的，且在±0.5之内的那些氨基酸取代是甚至更特别优选的。
本领域还了解可以基于疏水性有效地进行类似氨基酸的取代，特别是在意图将由此产生的生物功能等同性蛋白质或肽用于结合免疫学发明(本案就是如此)的情况中。蛋白质的最大局部平均亲水性(如由其相邻氨基酸的亲水性所决定的)与其免疫原性和抗原性，即与蛋白质的生物学特性相关联。已将下列亲水性数值(hydrophilicity value)赋予这些氨基酸残基：精氨酸(+3.0)；赖氨酸(+3.0)；天冬氨酸(+3.0±1)；谷氨酸(+3.0±1)；丝氨酸(+0.3)；天冬酰胺(+0.2)；谷氨酰胺(+0.2)；甘氨酸(0)；苏氨酸(-0.4)；脯氨酸(-0.5±1)；丙氨酸(-0.5)；组氨酸(-0.5)；半胱氨酸(-1.0)；甲硫氨酸(-1.3)；缬氨酸(-1.5)；亮氨酸(-1.8)；异亮氨酸(-1.8)；酪氨酸(-2.3)；苯丙氨酸(-2.5)；和色氨酸(-3.4)。在进行基于相似亲水性数值的变化时，亲水性数值在±2之内的氨基酸取代是优选的，在±1之内的那些氨基酸取代是特别优选的，且在±0.5之内的那些氨基酸取代是甚至更特别优选的。还可以基于亲水性鉴定来自一级氨基酸序列的表位。
在期望此类取代时，本领域技术人员可以确定期望的氨基酸取代(无论是保守的还是非保守的)。例如，可以使用氨基酸取代来鉴定HA蛋白的重要残基，或者提高或降低本文中描述的HA蛋白的免疫原性、溶解度或稳定性。下文在表I中显示了例示性的氨基酸取代。
表1
氨基酸取代
如本文中使用的，短语显著影响蛋白质活性指将蛋白质活性降低至少10％，至少20％，至少30％，至少40％或至少50％。就本发明而言，此类活性可以例如以蛋白质引发针对流感病毒的保护性抗体的能力测量。此类活性可以通过测量针对流感病毒的此类抗体的效价，此类抗体针对流感感染提供保护的能力或者通过测量由引发的抗体中和的类型、亚型或毒株的数目测量。测定抗体效价，实施保护测定法，和实施病毒中和测定法的方法是本领域技术人员已知的。在上文描述的活性外，可以测量的其它活性包括凝集红细胞的能力和蛋白质对细胞的结合亲和力。测量此类活性的方法是本领域技术人员已知的。
术语个体、受试者和患者是本领域中公知的，并且在本文中可互换使用，指对流感感染易感的任何人或其它动物。例子包括但不限于人和其它灵长类，包括非人灵长类，诸如黑猩猩及其它猿和猴物种；家畜，诸如牛、绵羊、猪、海豹、山羊和马；驯养哺乳动物，诸如犬和猫；实验室动物，包括啮齿类，诸如小鼠、大鼠和豚鼠；禽类，包括驯养禽类、野生禽类和猎禽，诸如鸡、火鸡和其它鸡形目(gallinaceous)禽类、鸭、鹅，等等。术语个体、受试者和患者单独不表示特定年龄、性别、人种，等等。因此，任何年龄的个体(无论雄性或雌性)意图为本公开内容覆盖，并且包括但不限于老年人、成人、儿童、婴孩(babies)、婴儿(infant)、和幼童(toddler)。同样地，本发明的方法可以适用于任何人种，包括例如高加索人(Caucasian)(白种人)、非洲裔美国人(African-American)(黑人)、美洲原住民(Native American)、夏威夷原住民(Native Hawaiian)、西班牙裔(Hispanic)、拉美裔(Latino)、亚裔(Asian)、和欧洲裔。感染的受试者是已知在其体内具有流感病毒的受试者。
如本文中使用的，接种疫苗的受试者是已经施用意图提供针对流感病毒的保护性效果的疫苗的受试者。
如本文中使用的，术语暴露指受试者已经与已知感染流感病毒的动物个体接触。
本文中讨论的出版物仅提供其在本申请的提交日前的公开内容。本文中的任何内容不应解释为承认凭借在先发明，本发明没有资格早于此类出版物。此外，提供的出版日期可以与实际出版日期不同，这可能需要独立确认。
除非另有定义，本文中使用的所有技术和科学术语与本发明所属领域的普通技术人员的通常理解具有相同的意义。虽然与本文中描述的方法和材料类似或等同的任何方法和材料也可以用于实施或测试本发明，现在描述优选的方法和材料。本文中提及的所有出版物通过提及收入本文以公开并描述与结合出版物引用的方法和/或材料。
应当领会，本发明的某些特征(为了清楚，其在不同实施方案的背景中描述)也可以在单一实施方案中组合提供。相反，本发明的各个特征(为了简洁，其在单一实施方案的背景中描述)也可以分开或在任何合适的亚组合中提供。实施方案的所有组合是本发明明确涵盖的，并且在本文中公开，就像每种组合单独且明确公开一样。另外，所有亚组合也是本发明明确涵盖的，并且在本文中公开，就像每种此类亚组合在本文中单独且明确公开一样。
本发明的一个实施方案是包含流感HA蛋白的蛋白质构建体，其中流感HA蛋白的头部区已被包含距HA蛋白头部区少于5个连续氨基酸残基的氨基酸序列替换。如本文中使用的，HA蛋白是指可用于产生本发明的蛋白质构建体和纳米颗粒的全长流感HA蛋白或其任何一个或多个部分和/或变体。因此，本发明涉及能够引发对流感HA蛋白的茎区的免疫应答的分子。在一些实施方案中，HA蛋白构建体的序列已经进一步改变(即突变)，以稳定蛋白的茎区，其形式可以呈递给免疫系统。此类HA蛋白的一些代表性实例和由其制备的蛋白质构建体示于下表2中。
表2
病毒表面上的三聚体HA蛋白包含球状头部区和茎或柄区域，其将HA蛋白锚定到病毒脂质包膜中。流感HA的头部区仅由HA1多肽的主要部分形成，而柄区由HA1和HA2的区段制成。根据本发明，头部区大致由对应于流感H1N1NC的全长HA蛋白(SEQ ID NO:8)的氨基酸59-291的HA蛋白的氨基酸组成。类似地，如本文所使用的，茎区大约由氨基酸1-58和对应于流感H1N1NC的全长HA蛋白(SEQ ID NO:8)的氨基酸328-564的HA蛋白的氨基酸组成。如本文中使用的，关于头部和茎区的术语大约是指上述序列在长度上可以改变几个氨基酸，而不影响本发明的性质。因此，例如，头部区可以由氨基酸50-291，氨基酸59-296或氨基酸59-285组成。通常，头部和茎区域将不会从上述位置改变超过十个氨基酸；然而，在一个实施方案中，头部区的羧基端末端可以延伸得远达对应于SEQ ID NO:8的氨基酸327的氨基酸。在一个实施方案中，头部区由在对应于流感A/新喀里多尼亚/20/1999(SEQ ID NO:8)的Cys59和Cys291的氨基酸残基之间的氨基酸序列组成，并且包括所述氨基酸残基。关于HA蛋白，本领域技术人员应当理解，来自不同流感病毒的HA蛋白可能由于蛋白质中的突变(插入，缺失)而具有不同的长度。因此，提及相应的区域是指与所比较的区域在序列、结构和/或功能上相同或几乎相同(例如，至少90％相同，至少95％相同，至少98％相同或至少99％相同)的另一种蛋白质的区域。例如，关于HA蛋白的茎区，另一HA蛋白中的相应区域可以不具有相同的残基数，但是将具有几乎相同的序列并且将执行相同的功能。作为实例，在上述实施方案中，来自A/新喀里多尼亚/20/1999的HA蛋白(SEQ ID NO:8)的头部区在氨基酸C291处结束。A/加利福尼亚/4/2009(H1)(SEQ ID NO:11)中头部区末端的相应氨基酸是半胱氨酸292。为了更好地阐明病毒之间的序列比较，本领域技术人员使用编号系统，其将氨基酸位置与参考序列相关。因此，来自不同流感毒株的HA蛋白中的相应氨基酸残基相对于其与蛋白质的n-末端氨基酸的距离可能不具有相同的残基数。例如，使用H3编号系统，参考A/新喀里多尼亚/20/1999(1999NC，H1)中的残基100并不意味着它是距离N-末端氨基酸的第100个残基。相反，A/新喀里多尼亚/20/1999(1999NC，H1)的残基100与流感H3N2毒株的残基100对齐。本领域技术人员理解这种编号系统的使用。虽然H3编号系统可用于鉴定氨基酸的位置，除非另有说明，HA蛋白中氨基酸残基的位置将通过一般性参考来自本文公开的序列的相应氨基酸的位置来鉴定。
本发明人还发现，通过将流感病毒HA蛋白的特定序列与能够将HA蛋白呈递给免疫系统的不相关分子组合，可以引发对HA蛋白的靶向区域的免疫应答。本发明的一个实施方案是包含与单体亚基蛋白的至少部分连接的流感HA蛋白的蛋白质构建体，其中流感HA蛋白的头部区已被包含来自HA蛋白的头部区的少于5个连续氨基酸残基的氨基酸序列替换，并且其中所述蛋白质构建体能够形成纳米颗粒。
通过至少将流感HA蛋白的部分与单体亚基连接，本发明的蛋白质构建体能够组装成在其表面上表达HA的三聚体的纳米颗粒。应当理解，构成此类三聚体的HA蛋白是融合前形式，并且与单体亚基的连接和在纳米颗粒上的表达使融合前蛋白以其三聚体形式稳定化。这是重大的，因为HA蛋白以更天然的形式呈现，意味着茎多肽的某些表面不被暴露，从而降低茎多肽可能诱导不利抗体应答的风险。
在一个实施方案中，HA蛋白包含来自流感HA蛋白的茎区的至少一个免疫原性部分，其中所述蛋白引发针对流感病毒的保护性抗体。在一个实施方案中，HA蛋白包含来自选自A型流感病毒，B型流感病毒和C型流感病毒的病毒的HA蛋白的茎区的至少一个免疫原性部分，其中蛋白质引发针对流感病毒的保护性抗体。在一个实施方案中，HA蛋白包含来自选自以下的HA蛋白的茎区的至少一个免疫原性部分：H1流感病毒HA蛋白，H2流感病毒HA蛋白，H3流感病毒HA蛋白，流感H4病毒HA蛋白，H5流感病毒HA蛋白，H6流感病毒HA蛋白，H7流感病毒HA蛋白，H8流感病毒HA蛋白，H9流感病毒HA蛋白，H10流感病毒HA蛋白HA蛋白，H11流感病毒HA蛋白，H12流感病毒HA蛋白，H13流感病毒HA蛋白，H14流感病毒HA蛋白，H15流感病毒HA蛋白，H16流感病毒HA蛋白，H17流感病毒HA蛋白和H18流感病毒HA蛋白。
在一个实施方案中，HA蛋白包含来自蛋白质的至少一个免疫原性部分，所述蛋白质包含与选自下组的序列至少80％相同的氨基酸序列：SEQ ID NO:8，SEQ ID NO:11，SEQID NO:14和SEQ ID NO:17。在一个实施方案中，HA蛋白包含来自蛋白质的至少一个免疫原性部分，所述蛋白质包含选自下组的氨基酸序列：SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17。在一个实施方案中，HA蛋白包含来自蛋白质的至少一个免疫原性部分，所述蛋白质包含与选自下组的序列至少80％相同的氨基酸序列：SEQ ID NO:80，SEQ IDNO:83，SEQ ID NO:86，SEQ ID NO:89，SEQ ID NO:92，SEQ ID NO:95，SEQ ID NO:98，SEQ IDNO:101，SEQ ID NO:104，SEQ ID NO:150，SEQ ID NO:152，SEQ ID NO:154，SEQ ID NO:156，SEQ ID NO:158，SEQ ID NO:164，SEQ ID NO:170，SEQ ID NO:176，SEQ ID NO:182，SEQ IDNO:188，SEQ ID NO:197，SEQ ID NO:203，SEQ ID NO:209，SEQ ID NO:214，SEQ ID NO:217，SEQ ID NO:222，SEQ ID NO:224，SEQ ID NO:226，SEQ ID NO:228，SEQ ID NO:230，SEQ IDNO:232，SEQ ID NO:235，SEQ ID NO:240，SEQ ID NO:242，SEQ ID NO:244，SEQ ID NO:246，SEQ ID NO:248，SEQ ID NO:250，SEQ ID NO:252，SEQ ID NO:254，SEQ ID NO:256，SEQ IDNO:258，SEQ ID NO:261，SEQ ID NO:268，SEQ ID NO:275，SEQ ID NO:282，SEQ ID NO:289，SEQ ID NO:296，SEQ ID NO:303，SEQ ID NO:310，SEQ ID NO:317，SEQ ID NO:324，SEQ IDNO:331，SEQ ID NO:338，SEQ ID NO:345，SEQ ID NO:352，SEQ ID NO:359，SEQ ID NO:366，SEQ ID NO:373，SEQ ID NO:380，SEQ ID NO:387，SEQ ID NO:394和SEQ ID NO:400。在一个实施方案中，HA蛋白包含来自蛋白质的至少一个免疫原性部分，所述蛋白质包含选自下组的氨基酸序列：SEQ ID NO:80，SEQ ID NO:83，SEQ ID NO:86，SEQ ID NO:89，SEQ ID NO:92，SEQ ID NO:95，SEQ ID NO:98，SEQ ID NO:101，SEQ ID NO:104，SEQ ID NO:150，SEQ IDNO:152，SEQ ID NO:154，SEQ ID NO:156，SEQ ID NO:158，SEQ ID NO:164，SEQ ID NO:170，SEQ ID NO:176，SEQ ID NO:182，SEQ ID NO:188，SEQ ID NO:197，SEQ ID NO:203，SEQ IDNO:209，SEQ ID NO:214，SEQ ID NO:217，SEQ ID NO:222，SEQ ID NO:224，SEQ ID NO:226，SEQ ID NO:228，SEQ ID NO:230，SEQ ID NO:232，SEQ ID NO:235，SEQ ID NO:240，SEQ IDNO:242，SEQ ID NO:244，SEQ ID NO:246，SEQ ID NO:248，SEQ ID NO:250，SEQ ID NO:252，SEQ ID NO:254，SEQ ID NO:256，SEQ ID NO:258，SEQ ID NO:261，SEQ ID NO:268，SEQ IDNO:275，SEQ ID NO:282，SEQ ID NO:289，SEQ ID NO:296，SEQ ID NO:303，SEQ ID NO:310，SEQ ID NO:317，SEQ ID NO:324，SEQ ID NO:331，SEQ ID NO:338，SEQ ID NO:345，SEQ IDNO:352，SEQ ID NO:359，SEQ ID NO:366，SEQ ID NO:373，SEQ ID NO:380，SEQ ID NO:387，SEQ ID NO:394和SEQ ID NO:400。在一个实施方案中，包含HA蛋白的免疫原性部分的此类蛋白质引发针对流感病毒的广泛保护性抗体的产生。
蛋白质的免疫原性部分包含表位，其是被免疫系统识别的氨基酸残基的簇，从而引发免疫应答。此类表位可以由连续的氨基酸残基(即，在蛋白质中彼此相邻的氨基酸残基)组成，或者它们可以由非连续的氨基酸残基(即，蛋白质中彼此不相邻的氨基酸残基)，但在最终折叠的蛋白质中紧密空间接近。本领域技术人员完全理解，表位需要最少六个氨基酸残基，以便被免疫系统识别。因此，在一个实施方案中，来自流感HA蛋白的免疫原性部分包含至少一个表位。在一个实施方案中，HA蛋白包含来自流感HA蛋白的茎区的至少6个氨基酸，至少10个氨基酸，至少25个氨基酸，至少50个氨基酸，至少75个氨基酸或至少100个氨基酸。在一个实施方案中，HA蛋白包含来自HA蛋白的茎区的至少6个氨基酸，至少10个氨基酸，至少25个氨基酸，至少50个氨基酸，至少75个氨基酸或至少100个氨基酸，所述HA蛋白来自选自A型流感病毒，B型流感病毒和C型流感病毒的病毒。在一个实施方案中，HA蛋白包含来自HA蛋白的茎区的至少6个氨基酸，至少10个氨基酸，至少25个氨基酸，至少50个氨基酸，至少75个氨基酸或至少100个氨基酸，所述HA蛋白来自选自H1流感病毒HA蛋白，H2流感病毒HA蛋白，H3流感病毒HA蛋白，H4流感病毒HA蛋白，H5流感病毒HA蛋白，H6流感病毒HA蛋白，H7流感病毒病毒HA蛋白，H8流感病毒HA蛋白，H9流感病毒HA蛋白，H10流感病毒HA蛋白HA蛋白，H11流感病毒HA蛋白，H12流感病毒HA蛋白，H13流感病毒HA蛋白，H14流感病毒HA蛋白，H15流感病毒HA蛋白，H16流感病毒HA蛋白，H17流感病毒HA蛋白和H18流感病毒HA蛋白。在一个实施方案中，HA蛋白包含来自HA蛋白的茎区的至少6个氨基酸，至少10个氨基酸，至少25个氨基酸，至少50个氨基酸，至少75个氨基酸或至少100个氨基酸，所述HA蛋白来自于选自下组的病毒株：流感A/新喀里多尼亚/20/1999(1999NC,H1),A/加利福尼亚/04/2009(2009CA,H1),A/新加坡/1/1957(1957Sing,H2),A/香港/1/1968(1968HK,H3),A/布里斯班/10/2007(2007Bris,H3),A/印度尼西亚/05/2005(2005Indo,H5),B/佛罗里达/4/2006(2006Flo,B),A/珀斯/16/2009(2009Per,H3),A/布里斯班/59/2007(2007Bris,H1),B/布里斯班/60/2008(2008Bris,B)及其变体。在一个实施方案中，氨基酸是来自HA蛋白的茎区的连续氨基酸。在一个实施方案中，包含来自HA蛋白的茎区的至少6个氨基酸，至少10个氨基酸，至少25个氨基酸，至少50个氨基酸，至少75个氨基酸或至少100个氨基酸的此类蛋白质引发针对流感病毒的广泛保护性抗体的产生。本发明的一个实施方案是包含蛋白质构建体，其包含来自HA蛋白的茎区的至少6个氨基酸，至少10个氨基酸，至少25个氨基酸，至少50个氨基酸，至少75个氨基酸或至少100个氨基酸，所述HA蛋白包含选自SEQ ID NO:8，SEQ ID NO:11，SEQ IDNO:14和SEQ ID NO:17的氨基酸序列。本发明的一个实施方案是蛋白质构建体，其包含来自HA蛋白的茎区的至少6个氨基酸，至少10个氨基酸，至少25个氨基酸，至少50个氨基酸，至少75个氨基酸或至少100个氨基酸，所述HA蛋白包含选自下组的氨基酸序列：SEQ ID NO:80,SEQ ID NO:83,SEQ ID NO:86,SEQ ID NO:89,SEQ ID NO:92,SEQ ID NO:95,SEQ ID NO:98,SEQ ID NO:101,SEQ ID NO:104,SEQ ID NO:150,SEQ ID NO:152,SEQ ID NO:154,SEQID NO:156,SEQ ID NO:158,SEQ ID NO:164,SEQ ID NO:170,SEQ ID NO:176,SEQ ID NO:182,SEQ ID NO:188,SEQ ID NO:197,SEQ ID NO:203,SEQ ID NO:209,SEQ ID NO:214,SEQID NO:217,SEQ ID NO:222,SEQ ID NO:224,SEQ ID NO:226,SEQ ID NO:228,SEQ ID NO:230,SEQ ID NO:232,SEQ ID NO:235,SEQ ID NO:240,SEQ ID NO:242,SEQ ID NO:244,SEQID NO:246,SEQ ID NO:248,SEQ ID NO:250,SEQ ID NO:252,SEQ ID NO:254,SEQ ID NO:256,SEQ ID NO:258,SEQ ID NO:261,SEQ ID NO:268,SEQ ID NO:275,SEQ ID NO:282,SEQID NO:289,SEQ ID NO:296,SEQ ID NO:303,SEQ ID NO:310,SEQ ID NO:317,SEQ ID NO:324,SEQ ID NO:331,SEQ ID NO:338,SEQ ID NO:345,SEQ ID NO:352,SEQ ID NO:359,SEQID NO:366,SEQ ID NO:373,SEQ ID NO:380,SEQ ID NO:387,SEQ ID NO:394和SEQ ID NO:400。在一个实施方案中，氨基酸是来自HA蛋白的茎区的连续氨基酸。在一个实施方案中，氨基酸是非连续的，但在最终蛋白质中紧密空间接近。
虽然本申请例示了来自几种示例性HA蛋白的茎区序列的使用，但是本发明也可以使用来自包含所公开的HA序列的变异的蛋白质的茎区来实施。因此，在一个实施方案中，HA蛋白来自选自下组的病毒：流感A/新喀里多尼亚/20/1999(1999NC,H1),A/加利福尼亚/04/2009(2009CA,H1),A/新加坡/1/1957(1957Sing,H2),A/香港/1/1968(1968HK,H3),A/布里斯班/10/2007(2007Bris,H3),A/印度尼西亚/05/2005(2005Indo,H5),B/佛罗里达/4/2006(2006Flo,B),A/珀斯/16/2009(2009Per,H3),A/布里斯班/59/2007(2007Bris,H1),B/布里斯班/60/2008(2008Bris,B)及其变体。在一个实施方案中，HA蛋白包含与HA蛋白的茎区至少80％，至少85％，至少90％，至少92％，至少94％，至少96％，至少98％或至少99％相同的氨基酸序列，所述HA蛋白包含选自下组的氨基酸序列：SEQ ID NO:8，SEQ ID NO:，SEQ IDNO:11，SEQ ID NO:14，SEQ ID NO:17。在一个实施方案中，HA蛋白包含选自SEQ ID NO:8，SEQ ID NO:,SEQ ID NO:11，SEQ ID NO:14，SEQ ID NO:17的氨基酸序列。
在一个实施方案中，HA蛋白的头部区序列被接头序列替换。可以使用任何接头序列，只要茎区序列能够形成期望的结构。虽然任何氨基酸可用于制备接头序列，但优选使用缺少大的或带电荷的侧链的氨基酸。优选的氨基酸包括但不限于丝氨酸，甘氨酸和丙氨酸。在一个实施方案中，接头由丝氨酸和甘氨酸残基制成。接头序列的长度可以变化，但是优选的实施方案使用最短的可能序列，以允许茎序列形成期望的结构。在一个实施方案中，接头序列的长度小于10个氨基酸。在一个实施方案中，接头序列的长度小于5个氨基酸。在优选的实施方案中，接头序列缺乏来自HA蛋白的头部区的连续氨基酸序列。在一个实施方案中，接头序列包含来自HA蛋白头部区的少于5个连续氨基酸。
如上所述，HA序列与单体亚基蛋白的部分连接。如本文中使用的，单体亚基蛋白是指能够结合其它单体亚基蛋白的蛋白单体，使得单体亚基蛋白自组装成纳米颗粒。任何单体亚基蛋白可以用于产生本发明的蛋白质构建体，只要该蛋白质构建体能够形成在其表面上展示HA蛋白的多聚体结构。在一个实施方案中，单体亚基是铁蛋白。
铁蛋白是在所有动物，细菌和植物中发现的球状蛋白，其主要通过将水合铁离子和质子运输到矿化核心和从矿化核心运输来控制多核Fe(III)2O3形成的速率和位置起作用。铁蛋白的球状形式由单体亚基蛋白(也称为单体铁蛋白亚基)组成，其是具有约17-20kDa的分子量的多肽。一个此类单体铁蛋白亚基的序列的实例由SEQ ID NO:2表示。每个单体铁蛋白亚基具有螺旋束的拓扑结构，其包括四个反向平行螺旋基序，具有大致垂直于4螺旋束的长轴的第五较短螺旋(c-端螺旋)。根据惯例，螺旋分别从N-末端标记为“A，B，C和D&E”。N-末端序列位于纳米颗粒三折轴附近并延伸到表面，而E螺旋在四折叠轴上聚集在一起，C-末端延伸到颗粒核心中。这种包装的结果在纳米颗粒表面上创建两个孔。预期这些孔中的一个或两个代表水合铁扩散进入和离开纳米颗粒的点。产生后，这些单体铁蛋白亚基蛋白自组装成球状铁蛋白蛋白。因此，铁蛋白的球状形式包含24个单体，铁蛋白亚基蛋白，并具有432对称的壳体样结构。
根据本发明，本发明的单体铁蛋白亚基是铁蛋白蛋白的全长单一多肽或其任何部分，其能够指导单体铁蛋白亚基自组装成蛋白质的球状形式。此类蛋白质的实例包括但不限于SEQ ID NO:2和SEQ ID NO:5。来自任何已知的铁蛋白蛋白的单体铁蛋白亚基的氨基酸序列可以用于产生本发明的蛋白质构建体，只要单体铁蛋白亚基能够自组装成在其表面上展示HA的纳米颗粒。在一个实施方案中，单体亚基来自选自下组的铁蛋白蛋白：细菌铁蛋白蛋白，植物铁蛋白蛋白，藻铁蛋白蛋白，昆虫铁蛋白蛋白，真菌铁蛋白蛋白和哺乳动物铁蛋白蛋白。在一个实施方案中，所述铁蛋白蛋白来自幽门螺杆菌(Helicobacter pylori)。
本发明的蛋白质构建体不需要包含铁蛋白蛋白的单体亚基多肽的全长序列。可以使用单体铁蛋白亚基蛋白的部分或区域，只要该部分包含指导单体铁蛋白亚基自组装成蛋白的球形形式的氨基酸序列。此类区域的一个实例位于幽门螺杆菌铁蛋白蛋白的氨基酸5和167之间。更具体的区域描述于Zhang,Y.Self-Assembly in the Ferritin Nano-CageProtein Super Family.2011,Int.J.Mol.Sci.,12,5406-5421，其通过引用整体并入本文。
在一个实施方案中，HA蛋白与来自铁蛋白的至少50个，至少100个或至少150个氨基酸连接，其中所述蛋白质构建体能够形成纳米颗粒。在一个实施方案中，HA蛋白与来自SEQ ID NO:2或SEQ ID NO:5的至少50，至少100或至少150个氨基酸连接，其中所述蛋白质构建体能够形成纳米颗粒。在一个实施方案中，HA蛋白与蛋白质连接，所述蛋白质包含与铁蛋白序列至少85％，至少90％或至少95％相同的氨基酸序列，其中蛋白质构建体能够形成纳米颗粒。在一个实施方案中，HA蛋白与蛋白质连接，所述蛋白质包含与SEQ ID NO:2或SEQID NO:5至少85％，至少90％，至少95％相同的氨基酸序列，其中所述蛋白质构建体形成纳米颗粒。
在一个实施方案中，单体亚基是2,4-二氧四氢蝶啶合成酶(lumazine synthase)。在一个实施方案中，HA蛋白与来自2,4-二氧四氢蝶啶合酶的至少50个，至少100个或至少150个氨基酸连接，其中所述蛋白质构建体能够形成纳米颗粒。因此，在一个实施方案中，HA蛋白与蛋白质连接，所述蛋白质与2,4-二氧四氢蝶啶合酶至少85％，至少90％，至少95％相同，其中蛋白质构建体能够形成纳米颗粒。
如本文中使用的，本发明的纳米颗粒是指通过本发明的蛋白质构建体(融合蛋白)的自组装形成的三维颗粒。本发明的纳米颗粒通常是球形形状的，尽管不排除其它形状，并且通常直径为约20nm至约100nm。本发明的纳米颗粒可以但不需要包含除了蛋白质构建体外的分子，如蛋白质，脂质，碳水化合物等，它们从所述蛋白质构建体中形成。
可以使用重组技术制备本发明的蛋白质构建体以将HA蛋白，接头和单体亚基的各部分连接在一起。以这种方式，可以产生仅包含产生纳米颗粒疫苗所必需的那些序列的蛋白质构建体。因此，本发明的一个实施方案是蛋白质构建体(也称为融合蛋白)，其包含来自流感病毒HA蛋白的茎区的第一氨基酸序列和来自流感病毒HA蛋白的茎区的第二氨基酸序列，所述第一和第二氨基酸序列通过接头序列共价连接，
其中所述第一氨基酸序列包含来自头部区序列的氨基端末端上游的氨基酸序列的至少20个连续氨基酸残基；
其中所述第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少20个连续氨基酸残基；和，
其中所述第一或第二氨基酸序列与单体亚基结构域的至少部分连接，使得所述蛋白质构建体能够形成纳米颗粒。
在一个实施方案中，第一氨基酸序列来自选自下组的病毒的HA蛋白的茎区：A型流感病毒，B型流感病毒和C型流感病毒。在一个实施方案中，第一氨基酸序列来自选自下组的病毒的HA蛋白的茎区：H1流感病毒，H2流感病毒，流感H3病毒，流感H4病毒，流感H5病毒，流感H6病毒，H7流感病毒，H8流感病毒，H9流感病毒，H10流感病毒，H11流感病毒，H12流感病毒，H13流感病毒，H14流感病毒，H15流感病毒，H16流感病毒，H17流感病毒，和H18流感病毒。在一个实施方案中，第一氨基酸序列来自选自下组的病毒的HA蛋白的茎区：流感A/新喀里多尼亚/20/1999(1999NC，H1)，A/加利福尼亚/04/2009(2009CA，H1)，A/新加坡/1/1957(1957Sing，H2)，A/香港/1/1968(1968HK，H3)，A/布里斯班/10/2007(2007Bris，H3)，A/印度尼西亚/05/2005(2005Indo，H5)，B/佛罗里达/4/2006(2006Flo，B)，A/珀斯/16/2009(2009Per，H3)，A/布里斯班/59/2007(2007Bris，H1)，B/布里斯班/60/2008(2008Bris，B)。在一个实施方案中，第一氨基酸序列来自HA蛋白的茎区，所述HA蛋白具有与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQ ID NO:8，SEQ IDNO:，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17。在一个实施方案中，第一氨基酸序列来自HA蛋白的茎区，所述HA蛋白包含选自下组的序列：SEQ ID NO:8，SEQ ID NO:11，SEQ IDNO:14和SEQ ID NO:17。在一个实施方案中，HA蛋白包含来自蛋白质的至少一个免疫原性部分，所述蛋白质包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQ ID NO:80，SEQ ID NO:83，SEQ ID NO:86，SEQ ID NO:89，SEQ ID NO:92，SEQID NO:95，SEQ ID NO:98，SEQ ID NO:101，SEQ ID NO:104，SEQ ID NO:150，SEQ ID NO:152，SEQ ID NO:154，SEQ ID NO:156，SEQ ID NO:158，SEQ ID NO:164，SEQ ID NO:170，SEQID NO:176，SEQ ID NO:182，SEQ ID NO:188，SEQ ID NO:197，SEQ ID NO:203，SEQ ID NO:209，SEQ ID NO:214，SEQ ID NO:217，SEQ ID NO:222，SEQ ID NO:224，SEQ ID NO:226，SEQID NO:228，SEQ ID NO:230，SEQ ID NO:232，SEQ ID NO:235，SEQ ID NO:240，SEQ ID NO:242，SEQ ID NO:244，SEQ ID NO:246，SEQ ID NO:248，SEQ ID NO:250，SEQ ID NO:252，SEQID NO:254，SEQ ID NO:256，SEQ ID NO:258，SEQ ID NO:261，SEQ ID NO:268，SEQ ID NO:275，SEQ ID NO:282，SEQ ID NO:289，SEQ ID NO:296，SEQ ID NO:303，SEQ ID NO:310，SEQID NO:317，SEQ ID NO:324，SEQ ID NO:331，SEQ ID NO:338，SEQ ID NO:345，SEQ ID NO:352，SEQ ID NO:359，SEQ ID NO:366，SEQ ID NO:373，SEQ ID NO:380，SEQ ID NO:387，SEQID NO:394和SEQ ID NO:400。在一个实施方案中，HA蛋白包含来自蛋白质的至少一个免疫原性部分，所述蛋白质包含选自下组的氨基酸序列：SEQ ID NO:80，SEQ ID NO:83，SEQ IDNO:86，SEQ ID NO:89，SEQ ID NO:92，SEQ ID NO:95，SEQ ID NO:98，SEQ ID NO:101，SEQID NO:104，SEQ ID NO:150，SEQ ID NO:152，SEQ ID NO:154，SEQ ID NO:156，SEQ ID NO:158，SEQ ID NO:164，SEQ ID NO:170，SEQ ID NO:176，SEQ ID NO:182，SEQ ID NO:188，SEQID NO:197，SEQ ID NO:203，SEQ ID NO:209，SEQ ID NO:214，SEQ ID NO:217，SEQ ID NO:222，SEQ ID NO:224，SEQ ID NO:226，SEQ ID NO:228，SEQ ID NO:230，SEQ ID NO:232，SEQID NO:235，SEQ ID NO:240，SEQ ID NO:242，SEQ ID NO:244，SEQ ID NO:246，SEQ ID NO:248，SEQ ID NO:250，SEQ ID NO:252，SEQ ID NO:254，SEQ ID NO:256，SEQ ID NO:258，SEQID NO:261，SEQ ID NO:268，SEQ ID NO:275，SEQ ID NO:282，SEQ ID NO:289，SEQ ID NO:296，SEQ ID NO:303，SEQ ID NO:310，SEQ ID NO:317，SEQ ID NO:324，SEQ ID NO:331，SEQID NO:338，SEQ ID NO:345，SEQ ID NO:352，SEQ ID NO:359，SEQ ID NO:366，SEQ ID NO:373，SEQ ID NO:380，SEQ ID NO:387，SEQ ID NO:394和SEQ ID NO:400。
在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：A型流感病毒，B型流感病毒和C型流感病毒。在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：H1流感病毒，H2流感病毒，流感H3病毒，流感H4病毒，流感H5病毒，流感H6病毒，H7流感病毒，H8流感病毒，H9流感病毒，H10流感病毒，H11流感病毒，H12流感病毒，H13流感病毒，H14流感病毒，H15流感病毒，H16流感病毒，H17流感病毒和H18流感病毒。在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：流感A/新喀里多尼亚/20/1999(1999NC，H1)，A/加利福尼亚/04/2009(2009CA，H1)，A/新加坡/1/1957(1957Sing，H2)，A/香港/1/1968(1968HK，H3)，A/布里斯班/10/2007(2007Bris，H3)，A/印度尼西亚/05/2005(2005Indo，H5)，B/佛罗里达/4/2006(2006Flo，B)，A/珀斯/16/2009(2009Per，H3)，A/布里斯班/59/2007(2007Bris，H1)，B/布里斯班/60/2008(2008Bris，B)。在一个实施方案中，第二氨基酸序列来自HA蛋白的茎区，所述HA蛋白具有与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17。在一个实施方案中，第二氨基酸序列来自HA蛋白的茎区，所述HA蛋白包含选自下组的序列：SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ IDNO:17。在一个实施方案中，HA蛋白包含来自蛋白质的至少一个免疫原性部分，所述蛋白质包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQID NO:80，SEQ ID NO:83，SEQ ID NO:86，SEQ ID NO:89，SEQ ID NO:92，SEQ ID NO:95，SEQID NO:98，SEQ ID NO:101，SEQ ID NO:104，SEQ ID NO:150，SEQ ID NO:152，SEQ ID NO:154，SEQ ID NO:156，SEQ ID NO:158，SEQ ID NO:164，SEQ ID NO:170，SEQ ID NO:176，SEQID NO:182，SEQ ID NO:188，SEQ ID NO:197，SEQ ID NO:203，SEQ ID NO:209，SEQ ID NO:214，SEQ ID NO:217，SEQ ID NO:222，SEQ ID NO:224，SEQ ID NO:226，SEQ ID NO:228，SEQID NO:230，SEQ ID NO:232，SEQ ID NO:235，SEQ ID NO:240，SEQ ID NO:242，SEQ ID NO:244，SEQ ID NO:246，SEQ ID NO:248，SEQ ID NO:250，SEQ ID NO:252，SEQ ID NO:254，SEQID NO:256，SEQ ID NO:258，SEQ ID NO:261，SEQ ID NO:268，SEQ ID NO:275，SEQ ID NO:282，SEQ ID NO:289，SEQ ID NO:296，SEQ ID NO:303，SEQ ID NO:310，SEQ ID NO:317，SEQID NO:324，SEQ ID NO:331，SEQ ID NO:338，SEQ ID NO:345，SEQ ID NO:352，SEQ ID NO:359，SEQ ID NO:366，SEQ ID NO:373，SEQ ID NO:380，SEQ ID NO:387，SEQ ID NO:394和SEQ ID NO:400。在一个实施方案中，HA蛋白包含来自蛋白质的至少一个免疫原性部分，所述蛋白质包含选自下组的氨基酸序列：SEQ ID NO:80，SEQ ID NO:83，SEQ ID NO:86，SEQID NO:89，SEQ ID NO:92，SEQ ID NO:95，SEQ ID NO:98，SEQ ID NO:101，SEQ ID NO:104，SEQ ID NO:150，SEQ ID NO:152，SEQ ID NO:154，SEQ ID NO:156，SEQ ID NO:158，SEQ IDNO:164，SEQ ID NO:170，SEQ ID NO:176，SEQ ID NO:182，SEQ ID NO:188，SEQ ID NO:197，SEQ ID NO:203，SEQ ID NO:209，SEQ ID NO:214，SEQ ID NO:217，SEQ ID NO:222，SEQ IDNO:224，SEQ ID NO:226，SEQ ID NO:228，SEQ ID NO:230，SEQ ID NO:232，SEQ ID NO:235，SEQ ID NO:240，SEQ ID NO:242，SEQ ID NO:244，SEQ ID NO:246，SEQ ID NO:248，SEQ IDNO:250，SEQ ID NO:252，SEQ ID NO:254，SEQ ID NO:256，SEQ ID NO:258，SEQ ID NO:261，SEQ ID NO:268，SEQ ID NO:275，SEQ ID NO:282，SEQ ID NO:289，SEQ ID NO:296，SEQ IDNO:303，SEQ ID NO:310，SEQ ID NO:317，SEQ ID NO:324，SEQ ID NO:331，SEQ ID NO:338，SEQ ID NO:345，SEQ ID NO:352，SEQ ID NO:359，SEQ ID NO:366，SEQ ID NO:373，SEQ IDNO:380，SEQ ID NO:387，SEQ ID NO:394和SEQ ID NO:400。
如上所述，第一氨基酸序列包含来自头部区序列的氨基端末端上游的氨基酸序列的至少20个连续氨基酸残基。根据本发明，术语上游指与头部区的第一个氨基酸残基的氨基端末端连接的氨基酸序列的全部。在一个实施方案中，头部区的氨基端末端位于对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白(SEQ ID NO:8)的Cys59的氨基酸残基。因此，在一个实施方案中，第一氨基酸序列包含来自对应于流感A新喀里多尼亚/20/1999(H1)(SEQID NO:8)的氨基酸残基1-58的HA蛋白区域的至少20个连续氨基酸残基。在一个实施方案中，第一氨基酸序列包含来自与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的序列的至少20个连续氨基酸残基：SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65。在一个实施方案中，第一氨基酸序列包含来自选自SEQ ID NO:20，SEQ IDNO:35，SEQ ID NO:50和SEQ ID NO:65的序列的至少20个连续氨基酸残基。
在一个实施方案中，第一氨基酸序列包含来自对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基1-58的HA蛋白的氨基酸区域的至少40个连续氨基酸残基。在一个实施方案中，第一氨基酸序列包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的序列的至少40个连续氨基酸残基：SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65。在一个实施方案中，第一氨基酸序列包含来自选自SEQ IDNO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65的序列的至少40个连续氨基酸残基。
在一个实施方案中，第一氨基酸序列包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的序列：SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ IDNO:65。在一个实施方案中，第一氨基酸序列包含选自SEQ ID NO:20，SEQ ID NO:35，SEQ IDNO:50和SEQ ID NO:65的序列。
在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：A型流感病毒，B型流感病毒和C型流感病毒。在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：H1流感病毒，H2流感病毒，H3流感病毒，H4流感病毒，H5流感病毒病毒，H6流感病毒，H7流感病毒，H8流感病毒，H9流感病毒，H10流感病毒，H11流感病毒，H12流感病毒，H13流感病毒，H14流感病毒，H15流感病毒病毒，H16流感病毒，H17流感病毒和H18流感病毒。在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：流感A/新喀里多尼亚/20/1999(1999NC,H1),A/加利福尼亚/04/2009(2009CA,H1),A/新加坡/1/1957(1957Sing,H2),A/香港/1/1968(1968HK,H3),A/布里斯班/10/2007(2007Bris,H3),A/印度尼西亚/05/2005(2005Indo,H5),B/佛罗里达/4/2006(2006Flo,B),A/珀斯/16/2009(2009Per,H3),A/布里斯班/59/2007(2007Bris,H1),B/布里斯班/60/2008(2008Bris,B)。在一个实施方案中，第二氨基酸序列来自HA蛋白的茎区，所述HA蛋白具有与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17。在一个实施方案中，第二氨基酸序列来自HA蛋白的茎区，所述HA蛋白包含选自SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17的序列。
如上所述，第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少20个连续氨基酸残基。根据本发明，术语下游指与头部区的羧基端末端氨基酸残基连接的整个氨基酸序列。在一个实施方案中，头部区的羧基端末端位于对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白(SEQ ID NO:8)的Cys291的氨基酸位置。因此，在一个实施方案中，第二氨基酸序列包含来自对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基292-517的HA蛋白的氨基酸区域的至少20个连续氨基酸。在一个实施方案中，第二氨基酸序列包含来自对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基328-517的HA蛋白的氨基酸区域的至少20个连续氨基酸。在一个实施方案中，第二氨基酸序列包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的序列的至少20个连续氨基酸残基：SEQ ID NO:23,SEQ ID NO:26,SEQ ID NO:29,SEQ ID NO:32,SEQID NO:38,SEQ ID NO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:53,SEQ ID NO:56,SEQID NO:59,SEQ ID NO:62,SEQ ID NO:68,SEQ ID NO:71,SEQ ID NO:74和SEQ ID NO:77。在一个实施方案中，第二氨基酸序列包含来自选自下组的序列的至少20个连续氨基酸残基：SEQ ID NO:23,SEQ ID NO:26,SEQ ID NO:29,SEQ ID NO:32,SEQ ID NO:38,SEQ ID NO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:53,SEQ ID NO:56,SEQ ID NO:59,SEQ IDNO:62,SEQ ID NO:68,SEQ ID NO:71,SEQ ID NO:74和SEQ ID NO:77。
在一个实施方案中，第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少40个，至少60个，至少75个，至少100个或至少150个连续氨基酸。在一个实施方案中，第二氨基酸序列包含来自HA蛋白的氨基酸区的至少40个，至少60个，至少75个，至少100个或至少150个连续氨基酸，所述氨基酸区对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基292-517。在一个实施方案中，第二氨基酸序列包含来自HA蛋白的氨基酸区域的至少40个，至少60个，至少75个，至少100个或至少150个连续氨基酸，所述氨基酸区域对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基328-517。在一个实施方案中，第二氨基酸序列包含来自序列的至少40，至少60，至少75，至少100或至少150个连续氨基酸，所述序列与选自下组的序列至少85％，至少90％，至少95％或至少97％相同：SEQ ID NO:23,SEQ ID NO:26,SEQ ID NO:29,SEQ ID NO:32,SEQ ID NO:38,SEQ ID NO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:53,SEQ ID NO:56,SEQ IDNO:59,SEQ ID NO:62,SEQ ID NO:68,SEQ ID NO:71,SEQ ID NO:74和SEQ ID NO:77。在一个实施方案中，第二氨基酸序列包含来自下组的至少40，至少60，至少75，至少100或至少150个连续氨基酸：SEQ ID NO:23,SEQ ID NO:26,SEQ ID NO:29,SEQ ID NO:32,SEQ IDNO:38,SEQ ID NO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:53,SEQ ID NO:56,SEQ IDNO:59,SEQ ID NO:62,SEQ ID NO:68,SEQ ID NO:71,SEQ ID NO:74和SEQ ID NO:77。在一个实施方案中，第二氨基酸序列包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQ ID NO:23,SEQ ID NO:26,SEQ ID NO:29,SEQ ID NO:32,SEQ ID NO:38,SEQ ID NO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:53,SEQ ID NO:56,SEQ ID NO:59,SEQ ID NO:62,SEQ ID NO:68,SEQ ID NO:71,SEQ ID NO:74和SEQ IDNO:77。在一个实施方案中，第二氨基酸序列包含选自下组的序列：SEQ ID NO:23,SEQ IDNO:26,SEQ ID NO:29,SEQ ID NO:32,SEQ ID NO:38,SEQ ID NO:41,SEQ ID NO:44,SEQ IDNO:47,SEQ ID NO:53,SEQ ID NO:56,SEQ ID NO:59,SEQ ID NO:62,SEQ ID NO:68,SEQ IDNO:71,SEQ ID NO:74和SEQ ID NO:77。
如上所述，蛋白质构建体的第一和第二氨基酸序列可以通过接头序列连接。可以使用任何接头序列，只要该接头序列具有距HA蛋白的头部区少于5个连续的氨基酸残基，并且只要第一和第二氨基酸能够形成期望的构象即可。在一个实施方案中，接头序列长度小于10个氨基酸，小于7个氨基酸或小于5个氨基酸。在一个实施方案中，接头序列包含甘氨酸和丝氨酸。在一个实施方案中，接头序列将第一氨基酸序列的羧基端末端连接到第二氨基酸序列的氨基端末端。在一个实施方案中，接头序列将第二氨基酸序列的羧基端末端连接到第一氨基酸序列的氨基端末端。
如上所述，蛋白质构建体的第一或第二氨基酸序列与单体亚基蛋白的至少部分连接，使得蛋白质构建体能够形成纳米颗粒。在一个实施方案中，单体亚基蛋白的至少部分连接到第二氨基酸序列。在优选的实施方案中，单体亚基蛋白的至少部分连接到第二氨基酸序列的羧基端末端。在一个实施方案中，所述部分包含来自单体亚基的至少50个，至少100个或至少150个氨基酸。在一个实施方案中，单体亚基是铁蛋白。在一个实施方案中，单体亚基是2,4-二氧四氢蝶啶合成酶。在一个实施方案中，所述部分包含来自SEQ ID NO:2，SEQID NO:5或SEQ ID NO:194的至少50，至少100或至少150个氨基酸。在一个实施方案中，单体亚基包含与SEQ ID NO:2，SEQ ID NO:5或SEQ ID NO:194具有至少85％相同，至少90％相同或至少95％相同的序列。在一个实施方案中，单体亚基包含选自SEQ ID NO:2，SEQ ID NO:5和SEQ ID NO:194的序列。
发明人已经发现，上述蛋白质构建体的流感HA序列的修饰导致蛋白质构建体的改进的稳定性。例如，本发明人已经发现，从对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白(SEQ ID NO:8)的氨基酸N403-W435的氨基酸区的HA蛋白的缺失导致更稳定的蛋白质构建体。在该区域缺失时，该区域侧翼的氨基酸序列可以直接连接在一起，或者它们可以用接头序列如例如甘氨酸-丝氨酸-甘氨酸连接。因此，在一个实施方案中，第二氨基酸序列包含与来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基至少85％，至少90％或至少95％相同的多肽序列，其中所述多肽序列缺少对应于来自流感A/新喀里多尼亚1999的HA蛋白(SEQ ID NO:8)的SEQ ID NO:133，SEQ ID NO:134，SEQ ID NO:135或SEQ ID NO:136的区域。在一个实施方案中，第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基，其中多肽序列缺乏对应于流感A/新喀里多尼亚1999的HA蛋白(SEQ ID NO:8)的SEQ ID NO:133，SEQ ID NO:134，SEQ IDNO:135或SEQ ID NO:136的区域。
在一个实施方案中，第二氨基酸序列包含与来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基至少85％，至少90％或至少95％相同的多肽序列，其中所述多肽序列缺少对应于流感A/加利福尼亚/4/2009的HA蛋白(SEQ ID NO:10)的SEQID NO:137，SEQ ID NO:138，SEQ ID NO:139或SEQ ID NO:140的区域。在一个实施方案中，第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基，其中多肽序列缺少对应于流感A/加利福尼亚/4/2009的HA蛋白(SEQ ID NO:10)的SEQ ID NO:137，SEQ ID NO:138，SEQ ID NO:139或SEQ ID NO:140的区域。
在一个实施方案中，第二氨基酸序列包含与来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基至少85％，至少90％或至少95％相同的氨基酸序列，其中多肽序列缺少对应于流感A/新加坡/1957的HA蛋白(SEQ ID NO:12)的SEQ ID NO:141，SEQ ID NO:142，SEQ ID NO:143或SEQ ID NO:144的区域。在一个实施方案中，第二氨基酸序列包含与来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基至少85％，至少90％或至少95％相同的氨基酸序列，其中多肽序列缺少对应于流感A/新加坡/1957的HA蛋白(SEQ ID NO:12)的SEQ ID NO:141，SEQ ID NO:142，SEQ ID NO:143或SEQ ID NO:144的区域。
在一个实施方案中，第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基，其中多肽序列缺少对应于流感A/印度尼西亚/05/2005(H5)的HA蛋白(SEQ ID NO:16)的SEQ ID NO:145，SEQ ID NO:146，SEQ ID NO:147或SEQ ID NO:148的区域。在一个实施方案中，第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基，其中多肽序列缺少对应于流感A/印度尼西亚/05/2005(H5)的HA蛋白(SEQ ID NO:16)的SEQ ID NO:145，SEQ ID NO:146，SEQID NO:147或SEQ ID NO:148的区域。
在一个实施方案中，第二氨基酸序列包含与SEQ ID NO:23，SEQ ID NO:26或SEQID NO:29的100个连续氨基酸至少85％，至少90％或至少95％相同的序列，其中所述100个连续氨基酸不包含选自SEQ ID NO:133，SEQ ID NO:134，SEQ ID NO:135和SEQ ID NO:136的序列。在一个实施方案中，第二氨基酸序列包含来自SEQ ID NO:23，SEQ ID NO:26或SEQID NO:29的100个连续氨基酸，其中所述100个连续氨基酸不包含选自下组的序列：SEQ IDNO:133，SEQ ID NO:134，SEQ ID NO:135和SEQ ID NO:136。
在一个实施方案中，第二氨基酸序列包含与SEQ ID NO:38，SEQ ID NO:41或SEQID NO:44的100个连续氨基酸至少85％，至少90％或至少95％相同的序列，其中所述100个连续氨基酸不包含选自SEQ ID NO:137，SEQ ID NO:138，SEQ ID NO:139和SEQ ID NO:140的序列。在一个实施方案中，第二氨基酸序列包含来自SEQ ID NO:38，SEQ ID NO:41或SEQID NO:44的100个连续氨基酸，其中所述100个连续氨基酸不包含选自下组的序列：SEQ IDNO:137，SEQ ID NO:138，SEQ ID NO:139和SEQ ID NO:140。
在一个实施方案中，第二氨基酸序列包含与SEQ ID NO:53，SEQ ID NO:56或SEQID NO:59的100个连续氨基酸至少85％，至少90％或至少95％相同的序列，其中所述100个连续氨基酸不包含选自SEQ ID NO:141，SEQ ID NO:142，SEQ ID NO:143和SEQ ID NO:144的序列。在一个实施方案中，第二氨基酸序列包含来自SEQ ID NO:53，SEQ ID NO:56或SEQID NO:59的100个连续氨基酸，其中所述100个连续氨基酸不包含选自下组的序列：SEQ IDNO:141，SEQ ID NO:142，SEQ ID NO:143和SEQ ID NO:144。
在一个实施方案中，第二氨基酸序列包含与SEQ ID NO:68，SEQ ID NO:71或SEQID NO:74的100个连续氨基酸至少85％，至少90％或至少95％相同的序列，其中所述100个连续氨基酸不包含选自SEQ ID NO:145，SEQ ID NO:146，SEQ ID NO:147和SEQ ID NO:148的序列。在一个实施方案中，第二氨基酸序列包含来自SEQ ID NO:68，SEQ ID NO:71或SEQID NO:74的100个连续氨基酸，其中所述100个连续氨基酸不包含选自下组的序列：SEQ IDNO:145，SEQ ID NO:146，SEQ ID NO:147和SEQ ID NO:148。
在一个实施方案中，第二氨基酸序列包含与来自选自下组的序列的100个连续氨基酸至少85％，至少90％或至少95％相同的序列：SEQ ID NO:26,SEQ ID NO:28,SEQ IDNO:32,SEQ ID NO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:56,SEQ ID NO:59,SEQ IDNO:62,SEQ ID NO:71和SEQ ID NO:77。在一个实施方案中，第二氨基酸序列包含来自选自下组的序列的至少100个连续氨基酸：SEQ ID NO:26,SEQ ID NO:32,SEQ ID NO:41,SEQ IDNO:47,SEQ ID NO:56,SEQ ID NO:62,SEQ ID NO:71和SEQ ID NO:77。在一个实施方案中，第二氨基酸序列包含选自下组的序列：SEQ ID NO:26,SEQ ID NO:32,SEQ ID NO:41,SEQID NO:47,SEQ ID NO:56,SEQ ID NO:62,SEQ ID NO:71,SEQ ID NO:74和SEQ ID NO:77。
本发明人还发现了，HA茎区序列的序列改变导致更稳定的蛋白质构建体。例如，在折叠的HA蛋白中，对应于流感A新喀里多尼亚/20/1999(H1)的K394和E446(对应于SEQ IDNO:149的K1和E53)的氨基酸残基形成盐桥，有助于稳定折叠的蛋白质。本发明人已经发现，通过用合适的氨基酸取代赖氨酸和谷氨酸残基，可以加强两个氨基酸残基之间的相互作用，这改善了分子的稳定性并允许对其进行更广泛的操作。因此，本发明的一个实施方案是蛋白质构建体，其包含来自流感病毒HA蛋白的茎区的第一氨基酸序列和来自流感病毒HA蛋白的茎区的第二氨基酸序列，所述第一和第二氨基酸酸序列通过接头序列共价连接，
其中所述第一氨基酸序列包含来自头部区序列的氨基端末端上游的氨基酸序列的至少20个连续氨基酸性残基，
其中所述第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少60个连续氨基酸，
其中所述60个连续氨基酸包含对应于来自A/新喀里多尼亚/20/1999的SEQ IDNO:149或SEQ ID NO:150的序列的多肽序列，且
其中对应于SEQ ID NO:149的K1或SEQ ID NO:150的K1的所述多肽序列中的氨基酸残基被除赖氨酸以外的氨基酸取代，
并且对应于SEQ ID NO:149的E53或SEQ ID NO:150的E20的氨基酸残基被除谷氨酸之外的氨基酸残基取代，使得取代的氨基酸残基之间的相互作用的强度大于在野生型蛋白中的相互作用的强度。
如上所述，对应于流感A新喀里多尼亚/20/1999(H1)的K394和E446的氨基酸残基形成盐桥，其是一类键。本领域已知存在氨基酸之间的其它类型的键，其强度根据键的类型而变化。此类键的实例包括但不限于疏水键和氢键，二者通常比盐桥更强。因此，在一个实施方案中，对应于SEQ ID NO:149的K1或SEQ ID NO:150的K1的多肽中的氨基酸残基和对应于SEQ ID NO:149的E53或SEQ ID NO:150的E20的多肽中的氨基酸残基被改变，使得它们在最终折叠的蛋白质中形成氢键。在一个实施方案中，对应于SEQ ID NO:149的K1或SEQ IDNO:150的K1的多肽中的氨基酸残基和对应于SEQ ID NO:149的E53或SEQ ID NO:150的E20的多肽中的氨基酸残基被改变，使得它们在最终折叠的蛋白质中形成疏水键。
对应于SEQ ID NO:149的K1，SEQ ID NO:150的K1，SEQ ID NO:149的E53或SEQ IDNO:150的E20的氨基酸可以被任何氨基酸残基取代，只要两个氨基酸之间的所得相互作用比未改变的蛋白质中的盐桥更强。增加对应于流感A新喀里多尼亚/20/1999(H1)的K394和E446(SEQ ID NO:149的K1和E53)的氨基酸之间的相互作用强度的取代的实例包括但不限于：
其中对应于SEQ ID NO:149的K1的多肽序列中的氨基酸残基被甲硫氨酸取代，并且对应于SEQ ID NO:149的E53的氨基酸残基被亮氨酸取代；
其中对应于SEQ ID NO:149的K1的多肽序列中的氨基酸残基被甲硫氨酸取代，并且对应于SEQ ID NO:149的E53的氨基酸残基被甲硫氨酸取代；
其中对应于SEQ ID NO:149的K1的多肽序列中的氨基酸残基被亮氨酸取代，并且对应于SEQ ID NO:149的E53的氨基酸残基被亮氨酸取代；
其中对应于SEQ ID NO:149的K1的多肽序列中的氨基酸残基被异亮氨酸取代，并且对应于SEQ ID NO:149的E53的氨基酸残基被异亮氨酸取代；
其中对应于SEQ ID NO:149的K1的多肽序列中的氨基酸残基被亮氨酸取代，并且对应于SEQ ID NO:149的E53的氨基酸残基被异亮氨酸取代；
其中对应于SEQ ID NO:149的K1的多肽序列中的氨基酸残基被谷氨酰胺取代，并且对应于SEQ ID NO:149的E53的氨基酸残基被谷氨酰胺取代。
在一个实施方案中，第一氨基酸序列来自选自下组的病毒的HA蛋白的茎区：A型流感病毒，B型流感病毒和C型流感病毒。在一个实施方案中，第一氨基酸序列来自选自下组的病毒的HA蛋白的茎区：H1流感病毒，H2流感病毒，流感H3病毒，流感H4病毒，流感H5病毒，流感H6病毒，H7流感病毒，H8流感病毒，H9流感病毒，H10流感病毒，H11流感病毒，H12流感病毒，H13流感病毒，H14流感病毒，H15流感病毒，H16流感病毒，H17流感病毒，和H18流感病毒。在一个实施方案中，第一氨基酸序列来自选自下组的病毒的HA蛋白的茎区：流感A/新喀里多尼亚/20/1999(1999NC，H1)，A/加利福尼亚/04/2009(2009CA，H1)，A/新加坡/1/1957(1957Sing，H2)，A/香港/1/1968(1968HK，H3)，A/布里斯班/10/2007(2007Bris，H3)，A/印度尼西亚/05/2005(2005Indo，H5)，B/佛罗里达/4/2006(2006Flo，B)，A/珀斯/16/2009(2009Per，H3)，A/布里斯班/59/2007(2007Bris，H1)，B/布里斯班/60/2008(2008Bris，B)。在一个实施方案中，第一氨基酸序列来自HA蛋白的茎区，所述HA蛋白具有与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17。在一个实施方案中，第一氨基酸序列来自HA蛋白的茎区，所述HA蛋白包含选自下组的序列：SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ IDNO:17。
在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：A型流感病毒，B型流感病毒和C型流感病毒。在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：H1流感病毒，H2流感病毒，流感H3病毒，流感H4病毒，流感H5病毒，流感H6病毒，H7流感病毒，H8流感病毒，H9流感病毒，H10流感病毒，H11流感病毒，H12流感病毒，H13流感病毒，H14流感病毒，H15流感病毒，H16流感病毒，H17流感病毒，和H18流感病毒。在一个实施方案中，第二氨基酸序列来自来自选自下组的病毒的HA蛋白的茎区：流感A/新喀里多尼亚/20/1999(1999NC，H1)，A/加利福尼亚/04/2009(2009CA，H1)，A/新加坡/1/1957(1957Sing，H2)，A/香港/1/1968(1968HK，H3)，A/布里斯班/10/2007(2007Bris，H3)，A/印度尼西亚/05/2005(2005Indo，H5)，B/佛罗里达/4/2006(2006Flo，B)，A/珀斯/16/2009(2009Per，H3)，A/布里斯班/59/2007(2007Bris，H1)，B/布里斯班/60/2008(2008Bris，B)。在一个实施方案中，第二氨基酸序列来自HA蛋白的茎区，所述HA蛋白具有与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列。在一个实施方案中，第二氨基酸序列来自HA蛋白的茎区，所述HA蛋白包含选自下组的序列：SEQ ID NO:8，SEQ IDNO:11，SEQ ID NO:14和SEQ ID NO:17。
在一个实施方案中，第一氨基酸序列包含来自对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基1-58的HA蛋白的区域的至少20个连续氨基酸残基。在一个实施方案中，第一氨基酸序列包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的序列的至少20个连续氨基酸残基：SEQ ID NO:20，SEQ ID NO:35，SEQ IDNO:50和SEQ ID NO:65。在一个实施方案中，第一氨基酸序列包含来自选自SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65的序列的至少20个连续氨基酸残基。
在一个实施方案中，第一氨基酸序列包含来自HA蛋白的氨基酸区域的至少40个连续氨基酸残基，所述氨基酸区域对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基1-58。在一个实施方案中，第一氨基酸序列包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的序列的至少40个连续氨基酸残基：SEQ ID NO:20，SEQID NO:35，SEQ ID NO:50和SEQ ID NO:65。在一个实施方案中，第一氨基酸序列包含来自选自SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65的序列的至少40个连续氨基酸残基。在一个实施方案中，第一氨基酸序列包含与选自下组的序列至少85％，至少90％或至少95％相同的序列：SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65。在一个实施方案中，第一氨基酸序列包含选自SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65的序列。
在一个实施方案中，第二氨基酸序列来自选自A型流感病毒，B型流感病毒和C型流感病毒的病毒的HA蛋白的茎区。在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：H1流感病毒，H2流感病毒，H3流感病毒，H4流感病毒，H5流感病毒病毒，H6流感病毒，H7流感病毒，H8流感病毒，H9流感病毒，H10流感病毒，H11流感病毒，H12流感病毒，H13流感病毒，H14流感病毒，H15流感病毒病毒，H16流感病毒，H17流感病毒和H18流感病毒。在一个实施方案中，第二氨基酸序列来自选自下组的病毒的HA蛋白的茎区：流感A/新喀里多尼亚/20/1999(1999NC,H1),A/加利福尼亚/04/2009(2009CA,H1),A/新加坡/1/1957(1957Sing,H2),A/香港/1/1968(1968HK,H3),A/布里斯班/10/2007(2007Bris,H3),A/印度尼西亚/05/2005(2005Indo,H5),B/佛罗里达/4/2006(2006Flo,B),A/珀斯/16/2009(2009Per,H3),A/布里斯班/59/2007(2007Bris,H1),B/布里斯班/60/2008(2008Bris,B)。在一个实施方案中，第二氨基酸序列来自HA蛋白的茎区，所述HA蛋白具有与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17。在一个实施方案中，第二氨基酸序列来自HA蛋白的茎区，所述HA蛋白包含选自SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17的序列。
在一个实施方案中，第二氨基酸序列的至少60个连续氨基酸来自HA蛋白的氨基酸区，所述氨基酸区对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基292-517。在一个实施方案中，第二氨基酸序列的至少60个连续氨基酸来自HA蛋白的氨基酸区，其对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基328-517。在一个实施方案中，第二氨基酸序列的至少60个连续氨基酸来自与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的序列：SEQ ID NO:23,SEQ ID NO:26,SEQ ID NO:29,SEQ ID NO:32,SEQ ID NO:38,SEQ ID NO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:53,SEQ ID NO:56,SEQ ID NO:59,SEQ ID NO:62,SEQ ID NO:68,SEQ ID NO:71,SEQ IDNO:74和SEQ ID NO:77。在一个实施方案中，第二氨基酸序列的至少60个连续氨基酸来自选自下组的序列
SEQ ID NO:23,SEQ ID NO:26,SEQ ID NO:29,SEQ ID NO:32,SEQ ID NO:38,SEQID NO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:53,SEQ ID NO:56,SEQ ID NO:59,SEQID NO:62,SEQ ID NO:68,SEQ ID NO:71,SEQ ID NO:74和SEQ ID NO:77。
在一个实施方案中，第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少75个，至少100个，至少150个或至少200个连续氨基酸，其中至少75个，至少100个，至少150个或至少200个连续氨基酸包含对应于H1N1NC的SEQ ID NO:149或SEQ IDNO:150的序列的多肽序列，并且其中对应于SEQ ID NO:149的K1或SEQ ID NO:150的K1的多肽序列中的氨基酸残基，和多肽序列中对应于SEQ ID NO:149的E53或SEQ ID NO:150的E20的氨基酸残基已经分别被除了赖氨酸和谷氨酸外的氨基酸取代，使得取代的氨基酸残基之间的相互作用的强度大于野生型蛋白质中的相互作用的强度。在一个实施方案中，第二氨基酸序列包含来自HA蛋白的氨基酸区域的至少75，至少100，至少150或至少200个连续氨基酸，所述HA蛋白对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基292-517，其中所述至少75个，至少100个，至少150个或至少200个连续氨基酸包含对应于H1N1NC的SEQ ID NO:149或SEQ ID NO:150的序列的多肽序列，并且其中对应于SEQ ID NO:149的K1或SEQ ID NO:150的K1的多肽序列中的氨基酸残基，和对应于SEQ ID NO:149的E53或SEQID NO:150的E20的多肽序列中的氨基酸残基分别被除了赖氨酸和谷氨酸之外的氨基酸取代，使得取代的氨基酸残基之间的相互作用的强度大于强度的野生型蛋白中的相互作用。在一个实施方案中，第二氨基酸序列包含来自HA蛋白的氨基酸区域的至少75个，至少100个，至少150个或至少200个连续氨基酸，所述氨基酸区域对应于流感A新喀里多尼亚/20/1999(H1)(SEQ ID NO:8)的氨基酸残基328-517，其中至少75，至少100，至少150或至少200个连续氨基酸包含对应于H1N1NC的SEQ ID NO:149或SEQ ID NO:150的序列的多肽序列，并且其中对应于SEQ ID NO:149的K1或SEQ ID NO:150的K1的多肽序列中的氨基酸残基，和对应于SEQ ID NO:149的E53或SEQ ID NO:150的E20的多肽序列中的氨基酸残基分别被除了赖氨酸和谷氨酸之外的氨基酸取代，使得取代的氨基酸残基之间的相互作用的强度大于强度的野生型蛋白中的相互作用。在一个实施方案中，第二氨基酸序列包含来自与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的序列的至少75，至少100，至少150或至少200个连续氨基酸：SEQ ID NO:23,SEQ ID NO:26,SEQ ID NO:29,SEQ ID NO:32,SEQID NO:38,SEQ ID NO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:53,SEQ ID NO:56,SEQID NO:59,SEQ ID NO:62,SEQ ID NO:68,SEQ ID NO:71,SEQ ID NO:74和SEQ ID NO:77，其中所述至少75个，至少100个，至少150个或至少200个连续氨基酸包含对应于H1N1NC的SEQID NO:149或SEQ ID NO:150的序列的多肽序列，和其中对应于SEQ ID NO:149的K1或SEQID NO:150的K1的多肽序列中的氨基酸残基和对应于SEQ ID NO:149的E53或SEQ ID NO:150的E20的多肽序列中的氨基酸残基分别被除了赖氨酸和谷氨酸之外的氨基酸取代，使得取代的氨基酸残基之间的相互作用的强度大于野生型蛋白质中相互作用的强度。在一个实施方案中，第二氨基酸序列包含来自下组的至少75，至少100，至少150或至少200个连续氨基酸：SEQ ID NO:23,SEQ ID NO:26,SEQ ID NO:29,SEQ ID NO:32,SEQ ID NO:38,SEQ IDNO:41,SEQ ID NO:44,SEQ ID NO:47,SEQ ID NO:53,SEQ ID NO:56,SEQ ID NO:59,SEQ IDNO:62,SEQ ID NO:68,SEQ ID NO:71,SEQ ID NO:74和SEQ ID NO:77。其中所述至少75个，至少100个，至少150个或至少200个连续氨基酸包含对应于H1N1NC的SEQ ID NO:149或SEQID NO:150的序列的多肽序列，并且其中对应于SEQ ID NO:149的K1或SEQ ID NO:150的K1的多肽序列中的氨基酸残基，并且多肽序列中对应于SEQ ID NO:149的E53或SEQ ID NO:150的E20的氨基酸残基已经分别被除了赖氨酸和谷氨酸之外的氨基酸取代，使得取代的氨基酸残基之间的相互作用的强度大于野生型蛋白质中的相互作用的强度。
含有规定位点特异性突变的蛋白质构建体可用于通过将本发明的纳米颗粒连接到单体亚基来制备本发明的纳米颗粒。因此，在一个实施方案中，将含有所公开的位点特异性突变(例如，SEQ ID NO:149或SEQ ID NO:150的K1和SEQ ID NO:149的E53或SEQ ID NO:150的E20)的蛋白质构建体连接到单体亚基蛋白的至少部分，其中所述单体亚基蛋白的所述部分能够指导蛋白质构建体的自组装。在一个实施方案中，单体亚基蛋白的至少部分连接到第二氨基酸序列。在优选的实施方案中，单体亚基蛋白的至少部分连接到第二氨基酸序列的羧基端末端。在一个实施方案中，所述部分包含来自单体亚基的至少50个，至少100个或至少150个氨基酸。在一个实施方案中，单体亚基是铁蛋白。在一个实施方案中，单体亚基是2,4-二氧四氢蝶啶合成酶。在一个实施方案中，单体亚基包含与SEQ ID NO:2，SEQ IDNO:5或SEQ ID NO:194至少85％相同，至少90％相同或至少95％相同的序列。在一个实施方案中，单体亚基包含选自SEQ ID NO:2，SEQ ID NO:5和SEQ ID NO:194的序列。
尽管对本文公开的HA蛋白进行的修饰已经描述为单独的实施方案，但是应当理解，所有此类修饰可以包含在单一蛋白质构建体中。例如，可以制备蛋白质构建体，其中第一氨基酸序列通过接头连接到第二氨基酸序列，其中第二氨基酸序列包含来自头部区的羧基端末端下游的区域的氨基酸序列，但是缺乏由SEQ ID NO:133-148表示的内部环序列，并且其中对应于SEQ ID NO:149的K1或SEQ ID NO:50的K1和SEQ ID NO:149的E53或SEQ IDNO:150的E20的第二氨基酸序列中的氨基酸分别被除了赖氨酸和谷氨酸之外的氨基酸取代，以增加折叠蛋白中这些氨基酸残基之间的相互作用的强度。因此，本发明的一个实施方案是蛋白质构建体，其包含来自流感病毒HA蛋白的茎区的第一氨基酸序列和来自流感病毒HA蛋白的茎区的第二氨基酸序列，所述第一和第二氨基酸酸序列通过接头序列共价连接，
其中所述第一氨基酸序列包含来自头部区序列的氨基端末端上游的氨基酸序列的至少20个连续氨基酸残基；
其中所述第二氨基酸序列包含与来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基至少85％，至少90％或至少95％相同的多肽序列，
其中所述多肽序列包含对应于由SEQ ID NO:150代表的流感A新喀里多尼亚/20/1999(H1)中的序列，由SEQ ID NO:152代表的流感A加利福尼亚/2009(H1)中的序列，由SEQID NO:154表示的流感A新加坡/1957(H2)中的序列和由SEQ ID NO:156表示的流感A印度尼西亚/2005H5)中的序列和，
其中对应于SEQ ID NO:150的K1的多肽序列中的氨基酸残基已经被除了赖氨酸之外的氨基酸取代，并且对应于SEQ ID NO:150的E20的氨基酸残基已经被除了谷氨酸外的氨基酸取代。
在一个实施方案中，多肽包含来自头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸。在一个实施方案中，所述至少100个连续氨基酸包含SEQ ID NO:150。在一个实施方案中，所述至少100个连续氨基酸包含SEQ ID NO:152。在一个实施方案中，所述至少100个连续氨基酸序列包含SEQ ID NO:154。在一个实施方案中，所述至少100个连续氨基酸包含SEQ ID NO:156。应当理解，在上述构建体中，当除去内部环区时，剩余的HA蛋白的各个末端可以直接连接在一起。然而，在一些情况下，此类直接连接可能降低肽主链的柔性。因此，在一些情况下，用接头序列替代内部环区域可能是有益的。作为实例，如果六个氨基酸接头序列插入SEQ ID NO:150，则最终序列可表现如下：VNSVIEKMGSGGSGTYNAELLVLL。
因此，在一个实施方案中，蛋白质构建体的多肽序列包含SEQ ID NO:150，其中插入短接头序列。在一个实施方案中，蛋白质构建体的多肽序列包含SEQ ID NO:152，其中插入短接头序列。在一个实施方案中，蛋白质构建体的多肽序列包含SEQ ID NO:154，其中插入短接头序列。在一个实施方案中，蛋白质构建体的多肽序列包含SEQ ID NO:156，其中插入短接头序列。在一个实施方案中，接头由丝氨酸和甘氨酸残基制成。在一个实施方案中，接头的长度少于10个氨基酸。在一个实施方案中，接头的长度少于5个氨基酸。在一个实施方案中，接头的长度少于3个氨基酸。
尽管上文所述的蛋白质构建体可用于产生能够产生针对一种或多种流感病毒的免疫应答的纳米颗粒，但是在一些实施方案中，可能有用的是将进一步的突变工程化改造到本发明的蛋白质的氨基酸序列中。例如，可以有用的是改变单体亚基蛋白，三聚化结构域或接头序列中的位点，如酶识别位点或糖基化位点，以便对蛋白质给予有益的性质(例如溶解度，半衰期，免于免疫监视的蛋白质的掩蔽部分)。在这方面，已知铁蛋白的单体亚基不是天然糖基化的。然而，如果其在哺乳动物或酵母细胞中作为分泌性蛋白质表达，则其可以被糖基化。因此，在一个实施方案中，来自单体铁蛋白亚基的氨基酸序列中的潜在N连接的糖基化位点被突变，使得突变的铁蛋白亚基序列在突变位点不再被糖基化。突变的单体铁蛋白亚基的一个此类序列由SEQ ID NO:5表示。
也可以改变蛋白质构建体序列以包括其它有用的突变。例如，在一些情况下，可以期望阻断针对蛋白质构建体中的某些氨基酸序列的免疫应答的产生。这可以通过在待阻断的位点附近添加糖基化位点来完成，使得聚糖在空间上阻碍免疫系统到达阻断位点的能力。因此，在一个实施方案中，蛋白质构建体的序列已经改变为包括一个或多个糖基化位点。这样的位点的实例包括但不限于Asn-X-Ser，Asn-X-Thr和Asn-X-Cys。在一些情况下，可以将糖基化位点引入接头序列中。引入糖基化位点的有用位点的其它实例包括但不限于对应于来自流感A新喀里多尼亚/20/1999(H1)的氨基酸45-47或氨基酸370-372的氨基酸。引入糖基化位点的方法是本领域技术人员已知的。
本文的公开内容证明在HA或单体亚基蛋白中的特定位置处的突变产生有用的蛋白质构建体，并因此产生本发明的纳米颗粒。引入突变的铁蛋白蛋白质中有用位置的实例包括对应于选自下组的氨基酸位置的氨基酸：SEQ ID NO:2的氨基酸位置18，氨基酸位置20和氨基酸位置68。引入突变的有用位置的实例包括HA蛋白中对应于选自下组的氨基酸位置的氨基酸：流感A新喀里多尼亚/20/1999(H1)的HA蛋白(SEQ ID NO:8)的氨基酸位置36，氨基酸位置45，氨基酸位置47，氨基酸位置49，氨基酸位置339，氨基酸位置340，氨基酸位置341，氨基酸位置342，氨基酸位置361，氨基酸位置372，氨基酸位置394，氨基酸位置402，氨基酸位置437，氨基酸位置438，氨基酸位置445，氨基酸位置446，氨基酸位置448，氨基酸449，氨基酸位置450和氨基酸位置452。表2中列出了此类突变的一些实例。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置36的位置处包含异亮氨酸或与其具有相似性质的氨基酸残基A。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置45的位置处包含天冬酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999的HA蛋白的氨基酸位置47的位置包含苏氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置49的位置处包含色氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置339的位置处包含谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置340的位置处包含精氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置341的位置包含谷氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置342的位置包含苏氨酸或与其具有相似性质的氨基酸残基(H1)。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置372的位置处包含苏氨酸或与其具有相似性质的氨基酸残基(H1)。在一个实施方案中，蛋白质构建体的HA部分在对应于在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置394的位置包含甲硫氨酸，异亮氨酸，亮氨酸，谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置402的位置处包含天冬酰胺，苏氨酸，甘氨酸，天冬酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置437的位置包含天冬氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置438的位置包含亮氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置445的位置包含亮氨酸，甲硫氨酸或具有与其相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置446的位置包含异亮氨酸，亮氨酸，甲硫氨酸，谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置448的位置处包含谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置449的位置包含色氨酸，苯丙氨酸或具有与其相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置450的位置处包含丙氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置452的位置处包含亮氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分缺少对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸515-517的一个或多个氨基酸。
本发明的一个实施方案是蛋白质构建体，所述蛋白质构建体包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQ ID NO:80,SEQ IDNO:83,SEQ ID NO:86,SEQ ID NO:89,SEQ ID NO:92,SEQ ID NO:95,SEQ ID NO:98,SEQ IDNO:101,SEQ ID NO:104,SEQ ID NO:158,SEQ ID NO:164,SEQ ID NO:170,SEQ ID NO:176,SEQ ID NO:182,SEQ ID NO:188,SEQ ID NO:197,SEQ ID NO:203,SEQ ID NO:209,SEQ IDNO:214,SEQ ID NO:217,SEQ ID NO:222,SEQ ID NO:224,SEQ ID NO:226,SEQ ID NO:228,SEQ ID NO:230,SEQ ID NO:232,SEQ ID NO:235,SEQ ID NO:240,SEQ ID NO:242,SEQ IDNO:244,SEQ ID NO:246,SEQ ID NO:248,SEQ ID NO:250,SEQ ID NO:252,SEQ ID NO:254,SEQ ID NO:256,SEQ ID NO:258,SEQ ID NO:261,SEQ ID NO:268,SEQ ID NO:275,SEQ IDNO:282,SEQ ID NO:289,SEQ ID NO:296,SEQ ID NO:303,SEQ ID NO:310,SEQ ID NO:317,SEQ ID NO:324,SEQ ID NO:331,SEQ ID NO:338,SEQ ID NO:345,SEQ ID NO:352,SEQ IDNO:359,SEQ ID NO:366,SEQ ID NO:373,SEQ ID NO:380,SEQ ID NO:387,SEQ ID NO:394和SEQ ID NO:400。
在一个实施方案中，对应于SEQ ID NO:149的K1或SEQ ID NO:150的K1的氨基酸残基的氨基酸残基被除了赖氨酸之外的氨基酸取代，并且对应于SEQ ID NO:149的E53的氨基酸残基或SEQ ID NO:20的E20的氨基酸残基被谷氨酸以外的氨基酸取代，使得在折叠蛋白中取代的氨基酸之间的相互作用的强度增加。
本发明的一个实施方案是蛋白质构建体，所述蛋白质构建体包含选自下组的序列：SEQ ID NO:80,SEQ ID NO:83,SEQ ID NO:86,SEQ ID NO:89,SEQ ID NO:92,SEQ IDNO:95,SEQ ID NO:98,SEQ ID NO:101,SEQ ID NO:104,SEQ ID NO:158,SEQ ID NO:164,SEQ ID NO:170,SEQ ID NO:176,SEQ ID NO:182,SEQ ID NO:188,SEQ ID NO:197,SEQ IDNO:203,SEQ ID NO:209,SEQ ID NO:214,SEQ ID NO:217,SEQ ID NO:222,SEQ ID NO:224,SEQ ID NO:226,SEQ ID NO:228,SEQ ID NO:230,SEQ ID NO:232,SEQ ID NO:235,SEQ IDNO:240,SEQ ID NO:242,SEQ ID NO:244,SEQ ID NO:246,SEQ ID NO:248,SEQ ID NO:250,SEQ ID NO:252,SEQ ID NO:254,SEQ ID NO:256,SEQ ID NO:258,SEQ ID NO:261,SEQ IDNO:268,SEQ ID NO:275,SEQ ID NO:282,SEQ ID NO:289,SEQ ID NO:296,SEQ ID NO:303,SEQ ID NO:310,SEQ ID NO:317,SEQ ID NO:324,SEQ ID NO:331,SEQ ID NO:338,SEQ IDNO:345,SEQ ID NO:352,SEQ ID NO:359,SEQ ID NO:366,SEQ ID NO:373,SEQ ID NO:380,SEQ ID NO:387,SEQ ID NO:394和SEQ ID NO:400。在一个实施方案中，当与单体亚基蛋白连接时，蛋白构建体能够形成纳米颗粒，其中纳米颗粒能够引发针对流感病毒的免疫应答。
如前已经描述，由流感HA蛋白制成的蛋白质构建体可以用于通过将其连接到单体亚基来制备本发明的纳米颗粒。因此，在一个实施方案中，蛋白质构建体与单体亚基蛋白质的至少一部分连接，其中单体亚基蛋白质的部分能够指导蛋白质构建体的自组装。在一个实施方案中，单体亚基蛋白的至少一部分连接到第二氨基酸序列。在优选的实施方案中，单体亚基蛋白的至少一部分连接到第二氨基酸序列的羧基末端。在一个实施方案中，所述部分包含来自单体亚基的至少50个，至少100个或至少150个氨基酸。在一个实施方案中，单体亚基是铁蛋白。在一个实施方案中，单体亚基是2,4-二氧四氢蝶啶合成酶。在一个实施方案中，单体亚基包含与SEQ ID NO:2，SEQ ID NO:5或SEQ ID NO:194至少85％相同，至少90％相同或至少95％相同的序列。在一个实施方案中，单体亚基包含选自SEQ ID NO:2，SEQ IDNO:5和SEQ ID NO:194的序列。
本发明的一个实施方案是蛋白质构建体，其包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的氨基酸序列：SEQ ID NO:107,SEQ ID NO:110,SEQ IDNO:113,SEQ ID NO:116,SEQ ID NO:119,SEQ ID NO:122,SEQ ID NO:125,SEQ ID NO:128,SEQ ID NO:131,SEQ ID NO:161,SEQ ID NO:167,SEQ ID NO:173,SEQ ID NO:179,SEQ IDNO:185,SEQ ID NO:191,SEQ ID NO:200,SEQ ID NO:206,SEQ ID NO:212,SEQ ID NO:215,SEQ ID NO:220,SEQ ID NO:223,SEQ ID NO:225,SEQ ID NO:227,SEQ ID NO:229,SEQ IDNO:231,SEQ ID NO:233,SEQ ID NO:238,SEQ ID NO:241,SEQ ID NO:243,SEQ ID NO:245,SEQ ID NO:247,SEQ ID NO:249,SEQ ID NO:251,SEQ ID NO:253,SEQ ID NO:255,SEQQ IDNO:257,SEQ ID NO:259,SEQ ID NO:264,SEQ ID NO:271,SEQ ID NO:278,SEQ ID NO:285,SEQ ID NO:292,SEQ ID NO:299,SEQ ID NO:306,SEQ ID NO:313,SEQ ID NO:320,SEQ IDNO:327,SEQ ID NO:334,SEQ ID NO:341,SEQ ID NO:348,SEQ ID NO:355,SEQ ID NO:362,SEQ ID NO:369,SEQ ID NO:376,SEQ ID NO:383,SEQ ID NO:390和SEQ ID NO:397。在一个实施方案中，对应于SEQ ID NO:149的K1或SEQ ID NO:150的K1的氨基酸残基被除了赖氨酸之外的氨基酸取代，并且对应于SEQ ID NO:149的E53的氨基酸残基或SEQ ID NO:20的E20被除了谷氨酸之外的氨基酸取代，使得在折叠蛋白中取代的氨基酸之间的相互作用的强度增加。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置36的位置包含异亮氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置45的位置处包含天冬酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置47的位置包含苏氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置49的位置处包含色氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置339的位置处包含谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置340的位置处包含精氨酸或与其具有相似性质的氨基酸残基(H1)。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/20的HA蛋白的氨基酸位置341的位置包含谷氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置342的位置包含苏氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置372的位置处包含苏氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置394的位置包含甲硫氨酸，异亮氨酸，亮氨酸，谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置402的位置处包含天冬酰胺，苏氨酸，甘氨酸，天冬酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置437的位置包含天冬氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置438的位置包含亮氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置445的位置包含亮氨酸，甲硫氨酸或具有与其相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置446的位置包含异亮氨酸，亮氨酸，甲硫氨酸，谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置448的位置处包含谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置449的位置包含色氨酸，苯丙氨酸或具有与其相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置450的位置处包含丙氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置452的位置处包含亮氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分缺少对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸515-517的一个或多个氨基酸。
本发明的一个实施方案是蛋白质构建体，所述蛋白质构建体包含选自下组的序列：SEQ ID NO:107,SEQ ID NO:110,SEQ ID NO:113,SEQ ID NO:116,SEQ ID NO:119,SEQID NO:122,SEQ ID NO:125,SEQ ID NO:128,SEQ ID NO:131,SEQ ID NO:161,SEQ ID NO:167,SEQ ID NO:173,SEQ ID NO:179,SEQ ID NO:185,SEQ ID NO:191,SEQ ID NO:200,SEQID NO:206,SEQ ID NO:212,SEQ ID NO:215,SEQ ID NO:220,SEQ ID NO:223,SEQ ID NO:225,SEQ ID NO:227,SEQ ID NO:229,SEQ ID NO:231,SEQ ID NO:233,SEQ ID NO:238,SEQID NO:241,SEQ ID NO:243,SEQ ID NO:245,SEQ ID NO:247,SEQ ID NO:249,SEQ ID NO:251,SEQ ID NO:253,SEQ ID NO:255,SEQQ ID NO:257,SEQ ID NO:259,SEQ ID NO:264,SEQ ID NO:271,SEQ ID NO:278,SEQ ID NO:285,SEQ ID NO:292,SEQ ID NO:299,SEQ IDNO:306,SEQ ID NO:313,SEQ ID NO:320,SEQ ID NO:327,SEQ ID NO:334,SEQ ID NO:341,SEQ ID NO:348,SEQ ID NO:355,SEQ ID NO:362,SEQ ID NO:369,SEQ ID NO:376,SEQ IDNO:383,SEQ ID NO:390和SEQ ID NO:397。
本发明的一个实施方案是由核酸分子编码的蛋白质构建体，所述核酸分子包含与选自下组的序列至少85％，至少90％，至少95％或至少97％相同的核酸序列：SEQ ID NO:266,SEQ ID NO:273,SEQ ID NO:SEQ ID NO:280,SEQ ID NO:287,SEQ ID NO:294,SEQ IDNO:301,SEQ ID NO:308,SEQ ID NO:315,SEQ ID NO:322,SEQ ID NO:329,SEQ ID NO:336,SEQ ID NO:343,SEQ ID NO:350,SEQ ID NO:357,SEQ ID NO:364,SEQ ID NO:371,SEQ IDNO:378,SEQ ID NO:385SEQ ID NO:392和SEQ ID NO:399。本发明的一个实施方案是由核酸分子编码的蛋白质构建体，所述核酸分子包含选自下组的核酸序列：SEQ ID NO:266,SEQID NO:273,SEQ ID NO:SEQ ID NO:280,SEQ ID NO:287,SEQ ID NO:294,SEQ ID NO:301,SEQ ID NO:308,SEQ ID NO:315,SEQ ID NO:322,SEQ ID NO:329,SEQ ID NO:336,SEQ IDNO:343,SEQ ID NO:350,SEQ ID NO:357,SEQ ID NO:364,SEQ ID NO:371,SEQ ID NO:378,SEQ ID NO:385SEQ ID NO:392和SEQ ID NO:399。
本发明的蛋白质和蛋白质构建体由本发明的核酸分子编码。此外，它们由本发明的核酸构建体表达。如本文所使用的，核酸构建体是重组表达载体，即连接到编码蛋白质的核酸分子的载体，使得当将核酸构建体施用于，例如，受试者或器官，组织或细胞时，核酸分子可以实现蛋白质表达。载体还能够将核酸分子转运到环境内的细胞，例如但不限于生物体，组织或细胞培养物。本公开的核酸构建体通过人类干预产生。核酸构建体可以是DNA，RNA或其变体。载体可以是DNA质粒，病毒载体或其它载体。在一个实施方案中，载体可以是巨细胞病毒(CMV)，逆转录病毒，腺病毒，腺伴随病毒，疱疹病毒，牛痘病毒，脊髓灰质炎病毒，辛德毕斯病毒或任何其它DNA或RNA病毒载体。在一个实施方案中，载体可以是假型化的慢病毒或逆转录病毒载体。在一个实施方案中，载体可以是DNA质粒。在一个实施方案中，载体可以是包含能够进行核酸分子递送和表达的病毒组分和质粒组分的DNA质粒。构建本公开的核酸构建体的方法是公知的。参见，例如，Molecular Cloning:a Laboratory Manual,3rd edition,Sambrook et al.2001Cold Spring Harbor Laboratory Press,以及CurrentProtocols in Molecular Biology,Ausubel et al.eds.,John Wiley&Sons,1994。在一个实施方案中，载体是DNA质粒，如CMV/R质粒，如CMV/R或CMV/R 8KB(本文也称为CMV/R 8kb)。本文提供了CMV/R和CMV/R 8kb的实例。CMV/R也在2006年8月22日授权的US 7,094,598B2中描述。
如本文中使用的，核酸分子包含编码本发明的蛋白质构建体的核酸序列。核酸分子可以重组地，合成地或通过重组和合成程序的组合产生。本公开的核酸分子可以具有野生型核酸序列或密码子修饰的核酸序列，以例如掺入由人翻译系统更好识别的密码子。在一个实施方案中，核酸分子可以被遗传工程化以引入或消除编码不同氨基酸的密码子，如引入编码N-连接的糖基化位点的密码子。产生本公开核酸分子的方法是本领域已知的，特别是一旦知道核酸序列。应当理解，核酸构建体可以包含一个核酸分子或多于一个核酸分子。还应当理解，核酸分子可以编码一种蛋白质或多于一种蛋白质。
一个实施方案是编码流感HA蛋白的核酸分子，所述流感HA蛋白包含与选自SEQ IDNO:150，SEQ ID NO:152，SEQ ID NO:154和SEQ ID NO:156的序列至少80％，至少85％，至少90％，至少92％，至少94％，至少96％，至少98％或至少99％相同的氨基酸序列。一个实施方案是编码流感HA蛋白的核酸分子，所述流感HA蛋白包含选自SEQ ID NO:150，SEQ ID NO:152，SEQ ID NO:154和SEQ ID NO:156的氨基酸序列。
在一个实施方案中，核酸分子编码流感HA蛋白，其包含与选自下组的序列至少80％，至少85％，至少90％，至少92％，至少94％，至少96％，至少98％或至少99％相同的氨基酸序列：SEQ ID NO:80,SEQ ID NO:83,SEQ ID NO:86,SEQ ID NO:89,SEQ ID NO:92,SEQID NO:95,SEQ ID NO:98,SEQ ID NO:101,SEQ ID NO:104,SEQ ID NO:158,SEQ ID NO:164,SEQ ID NO:170,SEQ ID NO:176,SEQ ID NO:182,SEQ ID NO:188,SEQ ID NO:197,SEQID NO:203,SEQ ID NO:209,SEQ ID NO:214,SEQ ID NO:217,SEQ ID NO:222,SEQ ID NO:224,SEQ ID NO:226,SEQ ID NO:228,SEQ ID NO:230,SEQ ID NO:232,SEQ ID NO:235,SEQID NO:240,SEQ ID NO:242,SEQ ID NO:244,SEQ ID NO:246,SEQ ID NO:248,SEQ ID NO:250,SEQ ID NO:252,SEQ ID NO:254,SEQ ID NO:256,SEQ ID NO:258,SEQ ID NO:261,SEQID NO:268,SEQ ID NO:275,SEQ ID NO:282,SEQ ID NO:289,SEQ ID NO:296,SEQ ID NO:303,SEQ ID NO:310,SEQ ID NO:317,SEQ ID NO:324,SEQ ID NO:331,SEQ ID NO:338,SEQID NO:345,SEQ ID NO:352,SEQ ID NO:359,SEQ ID NO:366,SEQ ID NO:373,SEQ ID NO:380,SEQ ID NO:387,SEQ ID NO:394和SEQ ID NO:400。在一个实施方案中，核酸分子编码流感HA蛋白，其包含选自下组的氨基酸：SEQ ID NO:80,SEQ ID NO:83,SEQ ID NO:86,SEQID NO:89,SEQ ID NO:92,SEQ ID NO:95,SEQ ID NO:98,SEQ ID NO:101,SEQ ID NO:104,SEQ ID NO:158,SEQ ID NO:164,SEQ ID NO:170,SEQ ID NO:176,SEQ ID NO:182,SEQ IDNO:188,SEQ ID NO:197,SEQ ID NO:203,SEQ ID NO:209,SEQ ID NO:214,SEQ ID NO:217,SEQ ID NO:222,SEQ ID NO:224,SEQ ID NO:226,SEQ ID NO:228,SEQ ID NO:230,SEQ IDNO:232,SEQ ID NO:235,SEQ ID NO:240,SEQ ID NO:242,SEQ ID NO:244,SEQ ID NO:246,SEQ ID NO:248,SEQ ID NO:250,SEQ ID NO:252,SEQ ID NO:254,SEQ ID NO:256,SEQ IDNO:258,SEQ ID NO:261,SEQ ID NO:268,SEQ ID NO:275,SEQ ID NO:282,SEQ ID NO:289,SEQ ID NO:296,SEQ ID NO:303,SEQ ID NO:310,SEQ ID NO:317,SEQ ID NO:324,SEQ IDNO:331,SEQ ID NO:338,SEQ ID NO:345,SEQ ID NO:352,SEQ ID NO:359,SEQ ID NO:366,SEQ ID NO:373,SEQ ID NO:380,SEQ ID NO:387,SEQ ID NO:394和SEQ ID NO:400。
本发明的一个实施方案是核酸分子，所述核酸分子包含与选自下组的序列至少80％，至少85％，至少90％，至少92％，至少94％，至少96％，至少98％或至少99％相同的核酸序列：SEQ ID NO:79,SEQ ID NO:82,SEQ ID NO:85,SEQ ID NO:88,SEQ ID NO:91,SEQID NO:94,SEQ ID NO:97,SEQ ID NO:100,SEQ ID NO:103,SEQ ID NO:157,SEQ ID NO:163,SEQ ID NO:169,SEQ ID NO:175,SEQ ID NO:181,SEQ ID NO:187,SEQ ID NO:196,SEQID NO:202,SEQ ID NO:208,SEQ ID NO:216,SEQ ID NO:234,SEQ ID NO:260,SEQ ID NO:267,SEQ ID NO:274,SEQ ID NO:281,SEQ ID NO:288,SEQ ID NO:295,SEQ ID NO:302,SEQID NO:309,SEQ ID NO:316,SEQ ID NO:323,SEQ ID NO:330,SEQ ID NO:337,SEQ ID NO:344,SEQ ID NO:351,SEQ ID NO:358,SEQ ID NO:365,SEQ ID NO:372,SEQ ID NO:379,SEQID NO:386和SEQ ID NO:393。本发明的一个实施方案是核酸分子，其包含选自下组的核酸：SEQ ID NO:79,SEQ ID NO:82,SEQ ID NO:85,SEQ ID NO:88,SEQ ID NO:91,SEQ ID NO:94,SEQ ID NO:97,SEQ ID NO:100,SEQ ID NO:103,SEQ ID NO:157,SEQ ID NO:163,SEQID NO:169,SEQ ID NO:175,SEQ ID NO:181,SEQ ID NO:187,SEQ ID NO:196,SEQ ID NO:202,SEQ ID NO:208,SEQ ID NO:216,SEQ ID NO:234,SEQ ID NO:260,SEQ ID NO:267,SEQID NO:274,SEQ ID NO:281,SEQ ID NO:288,SEQ ID NO:295,SEQ ID NO:302,SEQ ID NO:309,SEQ ID NO:316,SEQ ID NO:323,SEQ ID NO:330,SEQ ID NO:337,SEQ ID NO:344,SEQID NO:351,SEQ ID NO:358,SEQ ID NO:365,SEQ ID NO:372,SEQ ID NO:379,SEQ ID NO:386和SEQ ID NO:393。
优选的核酸分子是编码单体亚基，HA蛋白和/或包含与流感HA蛋白连接的单体亚基蛋白的蛋白质构建体的那些。因此，本发明的一个实施方案是包含编码蛋白质的核酸序列的核酸分子，所述蛋白质包含与流感HA蛋白连接的铁蛋白蛋白的单体亚基。在一个实施方案中，单体亚基包含与选自SEQ ID NO:2和SEQ ID NO:5的序列至少80％，至少85％，至少90％，至少92％，至少94％，至少96％，至少98％或至少99％序列相同的氨基酸序列。在一个实施方案中，单体亚基包含选自SEQ ID NO:2和SEQ ID NO:5的氨基酸序列。
本发明的一个实施方案是包含编码蛋白质的核酸序列的核酸分子，所述蛋白质包含与流感HA蛋白连接的2,4-二氧四氢蝶啶合酶单体亚基。在一个实施方案中，单体亚基包含与SEQ ID NO:194至少80％，至少85％，至少90％，至少92％，至少94％，至少96％，至少98％或至少99％相同的氨基酸序列。在一个实施方案中，单体亚基包含SEQ ID NO:194。
本发明的一个实施方案是编码蛋白质构建体的核酸分子，所述蛋白质构建体包含与选自下组的序列至少80％，至少85％，至少90％，至少92％，至少94％，至少96％，至少98％或至少99％相同的氨基酸序列：SEQ ID NO:107,SEQ ID NO:110,SEQ ID NO:113,SEQID NO:116,SEQ ID NO:119,SEQ ID NO:122,SEQ ID NO:125,SEQ ID NO:128,SEQ ID NO:131,SEQ ID NO:161,SEQ ID NO:167,SEQ ID NO:173,SEQ ID NO:179,SEQ ID NO:185,SEQID NO:191,SEQ ID NO:200,SEQ ID NO:206,SEQ ID NO:212,SEQ ID NO:215,SEQ ID NO:220,SEQ ID NO:223,SEQ ID NO:225,SEQ ID NO:227,SEQ ID NO:229,SEQ ID NO:231,SEQID NO:233,SEQ ID NO:238,SEQ ID NO:241,SEQ ID NO:243,SEQ ID NO:245,SEQ ID NO:247,SEQ ID NO:249,SEQ ID NO:251,SEQ ID NO:253,SEQ ID NO:255,SEQQ ID NO:257,SEQ ID NO:259,SEQ ID NO:264,SEQ ID NO:271,SEQ ID NO:278,SEQ ID NO:285,SEQ IDNO:292,SEQ ID NO:299,SEQ ID NO:306,SEQ ID NO:313,SEQ ID NO:320,SEQ ID NO:327,SEQ ID NO:334,SEQ ID NO:341,SEQ ID NO:348,SEQ ID NO:355,SEQ ID NO:362,SEQ IDNO:369,SEQ ID NO:376,SEQ ID NO:383,SEQ ID NO:390和SEQ ID NO:397。本发明的一个实施方案是编码蛋白质构建体的核酸分子，所述蛋白质构建体包含选自下组的序列：SEQID NO:107,SEQ ID NO:110,SEQ ID NO:113,SEQ ID NO:116,SEQ ID NO:119,SEQ ID NO:122,SEQ ID NO:125,SEQ ID NO:128,SEQ ID NO:131,SEQ ID NO:161,SEQ ID NO:167,SEQID NO:173,SEQ ID NO:179,SEQ ID NO:185,SEQ ID NO:191,SEQ ID NO:200,SEQ ID NO:206,SEQ ID NO:212,SEQ ID NO:215,SEQ ID NO:220,SEQ ID NO:223,SEQ ID NO:225,SEQID NO:227,SEQ ID NO:229,SEQ ID NO:231,SEQ ID NO:233,SEQ ID NO:238,SEQ ID NO:241,SEQ ID NO:243,SEQ ID NO:245,SEQ ID NO:247,SEQ ID NO:249,SEQ ID NO:251,SEQID NO:253,SEQ ID NO:255,SEQQ ID NO:257,SEQ ID NO:259,SEQ ID NO:264,SEQ ID NO:271,SEQ ID NO:278,SEQ ID NO:285,SEQ ID NO:292,SEQ ID NO:299,SEQ ID NO:306,SEQID NO:313,SEQ ID NO:320,SEQ ID NO:327,SEQ ID NO:334,SEQ ID NO:341,SEQ ID NO:348,SEQ ID NO:355,SEQ ID NO:362,SEQ ID NO:369,SEQ ID NO:376,SEQ ID NO:383,SEQID NO:390和SEQ ID NO:397。
本发明的一个实施方案是包含核酸序列的核酸分子，所述核酸序列与选自下组的序列至少80％，至少85％，至少90％，至少92％，至少94％，至少96％，至少98％或至少99％相同：SEQ ID NO:106,SEQ ID NO:109,SEQ ID NO:112,SEQ ID NO:115,SEQ ID NO:118,SEQ ID NO:121,SEQ ID NO:124,SEQ ID NO:127,SEQ ID NO:130,SEQ ID NO:160,SEQ IDNO:166,SEQ ID NO:172,SEQ ID NO:178,SEQ ID NO:184,SEQ ID NO:190,SEQ ID NO:199,SEQ ID NO:205,SEQ ID NO:211,SEQ ID NO:219,SEQ ID NO:237,SEQ ID NO:263,SEQ IDNO:270,SEQ ID NO:277,SEQ ID NO:284,SEQ ID NO:291,SEQ ID NO:298,SEQ ID NO:305,SEQ ID NO:312,SEQ ID NO:319,SEQ ID NO:326,SEQ ID NO:333,SEQ ID NO:340,SEQ IDNO:347,SEQ ID NO:354,SEQ ID NO:361,SEQ ID NO:368,SEQ ID NO:375,SEQ ID NO:382,SEQ ID NO:389和SEQ ID NO:396。本发明的一个实施方案是包含选自下组的核酸序列的核酸分子：SEQ ID NO:106,SEQ ID NO:109,SEQ ID NO:112,SEQ ID NO:115,SEQ ID NO:118,SEQ ID NO:121,SEQ ID NO:124,SEQ ID NO:127,SEQ ID NO:130,SEQ ID NO:160,SEQ IDNO:166,SEQ ID NO:172,SEQ ID NO:178,SEQ ID NO:184,SEQ ID NO:190,SEQ ID NO:199,SEQ ID NO:205,SEQ ID NO:211,SEQ ID NO:219,SEQ ID NO:237,SEQ ID NO:263,SEQ IDNO:270,SEQ ID NO:277,SEQ ID NO:284,SEQ ID NO:291,SEQ ID NO:298,SEQ ID NO:305,SEQ ID NO:312,SEQ ID NO:319,SEQ ID NO:326,SEQ ID NO:333,SEQ ID NO:340,SEQ IDNO:347,SEQ ID NO:354,SEQ ID NO:361,SEQ ID NO:368,SEQ ID NO:375,SEQ ID NO:382,SEQ ID NO:389和SEQ ID NO:396。
本发明还涵盖用于产生本发明的蛋白质构建体的表达系统。在一个实施方案中，本发明的核酸分子可操作地连接于启动子。如本文中使用的，操作连接是指当连接的启动子被激活时，可以表达由连接的核酸分子编码的蛋白质。用于实施本发明的启动子是本领域技术人员已知的。本发明的一个实施方案是包含核酸序列的核酸分子，所述核酸序列与选自下组的序列至少85％，至少90％，至少95％或至少97％相同：SEQ ID NO:266,SEQ IDNO:273,SEQ ID NO:SEQ ID NO:280,SEQ ID NO:287,SEQ ID NO:294,SEQ ID NO:301,SEQID NO:308,SEQ ID NO:315,SEQ ID NO:322,SEQ ID NO:329,SEQ ID NO:336,SEQ ID NO:343,SEQ ID NO:350,SEQ ID NO:357,SEQ ID NO:364,SEQ ID NO:371,SEQ ID NO:378,SEQID NO:385SEQ ID NO:392和SEQ ID NO:399。本发明的一个实施方案是包含选自下组的核酸序列的核酸分子：SEQ ID NO:266,SEQ ID NO:273,SEQ ID NO:SEQ ID NO:280,SEQ IDNO:287,SEQ ID NO:294,SEQ ID NO:301,SEQ ID NO:308,SEQ ID NO:315,SEQ ID NO:322,SEQ ID NO:329,SEQ ID NO:336,SEQ ID NO:343,SEQ ID NO:350,SEQ ID NO:357,SEQ IDNO:364,SEQ ID NO:371,SEQ ID NO:378,SEQ ID NO:385SEQ ID NO:392和SEQ ID NO:399。
本发明的一个实施方案是包含本发明的核酸分子的重组细胞。本发明的一个实施方案是包含本发明的核酸分子的重组病毒。
如上指示，本发明的蛋白质构建体的重组生产可以使用本领域目前已知的任何合适的常规重组技术来完成。例如，可以如下在大肠杆菌(E.coli)中进行编码融合蛋白的核酸分子的产生，即使用编码合适的单体亚基蛋白(如幽门螺杆菌铁蛋白单体亚基)的核酸分子，并且将其融合到编码本文公开的合适的流感蛋白的核酸分子。然后，可以将构建体转化成蛋白质表达细胞，培养至合适的大小，并诱导产生融合蛋白。
如已经描述的，因为本发明的蛋白质构建体包含单体亚基蛋白质，所以它们可以自组装。根据本发明，由此类自组装产生的超分子被称为HA表达性、基于单体亚基的纳米颗粒。为了便于讨论，将HA表达性、基于单体亚基的纳米颗粒简称为纳米颗粒(np)。本发明的纳米颗粒具有与制备它们的单体蛋白质的纳米颗粒相似的结构特征。例如，关于铁蛋白，基于铁蛋白的纳米颗粒含有24个亚基并且具有432对称性。在本发明的纳米颗粒的情况下，亚基是包含与流感HA蛋白连接的单体亚基(例如，铁蛋白，2,4-二氧四氢蝶啶合酶等)的蛋白质构建体。此类纳米颗粒在其表面上以HA三聚体展示HA蛋白的至少一部分。在此类构建中，HA三聚体对于免疫系统是可及的，并且因此可以引发免疫应答。因此，本发明的一个实施方案是包含本发明的蛋白构建体的纳米颗粒，其中所述蛋白构建体包含来自与单体亚基蛋白连接的HA蛋白的茎区的氨基酸。在一个实施方案中，纳米颗粒在其表面上以HA三聚体展示HA蛋白。在一个实施方案中，流感HA蛋白能够引发针对流感病毒的保护性抗体。
在本发明的一个实施方案中，纳米颗粒包含蛋白质构建体，其包含来自流感病毒HA蛋白的茎区的第一氨基酸序列和来自流感病毒HA蛋白的茎区的第二氨基酸序列，所述第一和第二氨基酸序列通过接头序列共价连接，
其中所述第一氨基酸序列包含来自头部区序列的氨基端末端上游的氨基酸序列的至少20个连续氨基酸残基；
其中所述第二氨基酸序列包含来自所述头部区序列的羧基端末端下游的氨基酸序列的至少20个连续氨基酸残基；且
其中所述第一或第二氨基酸序列与单体亚基结构域的至少一部分连接。
在本发明的一个实施方案中，纳米颗粒包含蛋白质构建体，其包含来自流感病毒HA蛋白的茎区的第一氨基酸序列和来自流感病毒HA蛋白的茎区的第二氨基酸序列，所述第一和第二氨基酸序列通过接头序列共价连接，
其中所述第一氨基酸序列包含来自头部区序列的氨基端末端上游的氨基酸序列的至少20个连续氨基酸残基；
其中所述第二氨基酸序列包含与头部区序列的羧基端末端下游的氨基酸序列的至少100个连续氨基酸残基至少85％，至少90％或至少95％相同的多肽序列，
其中所述多肽序列包含与由SEQ ID NO:150代表的流感A新喀里多尼亚/20/1999(H1)中的序列，由SEQ ID NO:150代表的流感A加利福尼亚/2009中的序列，由SEQ ID NO:154代表的流感A新加坡/1957(H2)中的序列和由SEQ ID NO:156代表的流感A印度尼西亚/2005H5中的序列对应的序列；和
其中所述第一或第二氨基酸序列与单体亚基蛋白连接。
在另一个实施方案中，多肽序列中对应于SEQ ID NO:150的K1的氨基酸残基已被除赖氨酸以外的氨基酸取代，并且对应于SEQ ID NO:150的E20的氨基酸残基已经被除谷氨酸以外的氨基酸取代。
在一个实施方案中，在构成纳米颗粒的蛋白质构建体的单体亚基部分和/或第一和/或第二氨基酸序列中进行了另外的突变。引入突变的铁蛋白蛋白质中有用位置的实例包括对应于选自下组的氨基酸位置的氨基酸：SEQ ID NO:2的氨基酸位置18，氨基酸位置20和氨基酸位置68。在一个实施方案中，蛋白质构建体包含在对应于选自下组的氨基酸位置的氨基酸位置处的突变：流感A新喀里多尼亚/20/1999(H1)的HA蛋白(SEQ ID NO:8)的氨基酸位置36，氨基酸位置45，氨基酸位置47，氨基酸位置49，氨基酸位置339，氨基酸位置340，氨基酸位置341，氨基酸位置342，氨基酸位置361，氨基酸位置372，氨基酸位置394，氨基酸位置402，氨基酸位置437，氨基酸位置438，氨基酸位置445，氨基酸位置446，氨基酸位置448，氨基酸449，氨基酸位置450和氨基酸位置452。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置36的位置包含异亮氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置45的位置处包含天冬酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置47的位置包含苏氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置49的位置处包含色氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置339的位置处包含谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置340的位置处包含精氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置341的位置包含谷氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置342的位置包含苏氨酸或与其具有相似性质的氨基酸残基(H1)。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置372的位置处包含苏氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置394的位置包含甲硫氨酸，异亮氨酸，亮氨酸，谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置402的位置处包含天冬酰胺，苏氨酸，甘氨酸，天冬酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置437的位置包含天冬氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置438的位置包含亮氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置445的位置包含亮氨酸，甲硫氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置446的位置包含异亮氨酸，亮氨酸，甲硫氨酸，谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置448的位置处包含谷氨酰胺或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置449的位置包含色氨酸，苯丙氨酸或具有与其相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置450的位置处包含丙氨酸或与其具有相似性质的氨基酸残基。在一个实施方案中，蛋白质构建体的HA部分在对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸位置452的位置处包含亮氨酸或与其具有相似性质的氨基酸残基(H1)。在一个实施方案中，蛋白质构建体的HA部分缺少对应于流感A新喀里多尼亚/20/1999(H1)的HA蛋白的氨基酸515-517的一个或多个氨基酸。
在一个实施方案中，本发明的纳米颗粒包含单体亚基蛋白，其包含来自2,4-二氧四氢蝶啶合酶的至少50个氨基酸，至少100个氨基酸或至少150个氨基酸。在一个实施方案中，单体亚基蛋白包含来自选自SEQ ID NO:194的氨基酸序列的至少50个氨基酸，至少100个氨基酸或至少150个氨基酸，和/或包含与SEQ ID NO:194至少85％，至少90％，至少95％，至少97％，至少99％相同的氨基酸序列。在一个实施方案中，单体亚基包含SEQ ID NO:194。
在一个实施方案中，单体亚基蛋白包含来自铁蛋白蛋白的至少50个氨基酸，至少100个氨基酸或至少150个氨基酸。在一个实施方案中，单体亚基蛋白包含来自选自SEQ IDNO:2和SEQ ID NO:5的氨基酸序列的至少50个氨基酸，至少100个氨基酸或至少150个氨基酸，和或包含与选自SEQ ID NO:2和SEQ ID NO:5的氨基酸序列至少85％，至少90％，至少95％，至少97％，至少99％相同的氨基酸序列。在一个实施方案中，单体铁蛋白亚基包含SEQID NO:2或SEQ ID NO:5。
在一个实施方案中，纳米颗粒包含蛋白质构建体，其包含与来自病毒的HA蛋白的至少一个免疫原性部分连接的本发明的单体蛋白质，所述病毒选自A型流感病毒，B型流感病毒和C型流感病毒。在一个实施方案中，蛋白质构建体包含与选自下组的HA蛋白的至少一个免疫原性部分连接的本发明的单体蛋白：H1流感病毒HA蛋白，H2流感病毒HA蛋白，H3流感病毒HA蛋白，H4流感病毒HA蛋白，H5流感病毒HA蛋白，H6流感病毒HA蛋白，H7流感病毒HA蛋白，H8流感病毒HA蛋白，H9流感病毒HA蛋白，H10流感病毒HA蛋白，H11流感病毒HA蛋白，H12流感病毒HA蛋白，H13流感病毒HA蛋白，H14流感病毒HA蛋白，H15流感病毒HA蛋白，H16流感病毒HA蛋白，H17流感病毒HA蛋白，和H18流感病毒HA蛋白。在一个实施方案中，免疫原性部分包含至少一个表位。
在一个实施方案中，纳米颗粒包含包含蛋白质构建体，所述蛋白质构建体包含与氨基酸序列连接的本发明的单体蛋白，所述氨基酸序列与选自下组的序列是至少约80％，至少约85％，至少约90％，至少约95％，至少约97％或至少约99％相同的：SEQ ID NO:80,SEQ ID NO:83,SEQ ID NO:86,SEQ ID NO:89,SEQ ID NO:92,SEQ ID NO:95,SEQ ID NO:98,SEQ ID NO:101,SEQ ID NO:104,SEQ ID NO:158,SEQ ID NO:164,SEQ ID NO:170,SEQID NO:176,SEQ ID NO:182,SEQ ID NO:188,SEQ ID NO:197,SEQ ID NO:203,SEQ ID NO:209,SEQ ID NO:214,SEQ ID NO:217,SEQ ID NO:222,SEQ ID NO:224,SEQ ID NO:226,SEQID NO:228,SEQ ID NO:230,SEQ ID NO:232,SEQ ID NO:235,SEQ ID NO:240,SEQ ID NO:242,SEQ ID NO:244,SEQ ID NO:246,SEQ ID NO:248,SEQ ID NO:250,SEQ ID NO:252,SEQID NO:254,SEQ ID NO:256,SEQ ID NO:258,SEQ ID NO:261,SEQ ID NO:268,SEQ ID NO:275,SEQ ID NO:282,SEQ ID NO:289,SEQ ID NO:296,SEQ ID NO:303,SEQ ID NO:310,SEQID NO:317,SEQ ID NO:324,SEQ ID NO:331,SEQ ID NO:338,SEQ ID NO:345,SEQ ID NO:352,SEQ ID NO:359,SEQ ID NO:366,SEQ ID NO:373,SEQ ID NO:380,SEQ ID NO:387,SEQID NO:394和SEQ ID NO:400，其中蛋白质构建体能够选择性结合抗流感抗体。在一个实施方案中，纳米颗粒包含蛋白质构建体，所述蛋白质构建体包含与氨基酸序列连接的本发明的单体蛋白，所述氨基酸序列选自下组：SEQ ID NO:80,SEQ ID NO:83,SEQ ID NO:86,SEQID NO:89,SEQ ID NO:92,SEQ ID NO:95,SEQ ID NO:98,SEQ ID NO:101,SEQ ID NO:104,SEQ ID NO:158,SEQ ID NO:164,SEQ ID NO:170,SEQ ID NO:176,SEQ ID NO:182,SEQ IDNO:188,SEQ ID NO:197,SEQ ID NO:203,SEQ ID NO:209,SEQ ID NO:214,SEQ ID NO:217,SEQ ID NO:222,SEQ ID NO:224,SEQ ID NO:226,SEQ ID NO:228,SEQ ID NO:230,SEQ IDNO:232,SEQ ID NO:235,SEQ ID NO:240,SEQ ID NO:242,SEQ ID NO:244,SEQ ID NO:246,SEQ ID NO:248,SEQ ID NO:250,SEQ ID NO:252,SEQ ID NO:254,SEQ ID NO:256,SEQ IDNO:258,SEQ ID NO:261,SEQ ID NO:268,SEQ ID NO:275,SEQ ID NO:282,SEQ ID NO:289,SEQ ID NO:296,SEQ ID NO:303,SEQ ID NO:310,SEQ ID NO:317,SEQ ID NO:324,SEQ IDNO:331,SEQ ID NO:338,SEQ ID NO:345,SEQ ID NO:352,SEQ ID NO:359,SEQ ID NO:366,SEQ ID NO:373,SEQ ID NO:380,SEQ ID NO:387,SEQ ID NO:394和SEQ ID NO:400，其中蛋白质构建体能够选择性结合抗流感抗体。
在本发明的一个实施方案中，纳米颗粒包含蛋白质构建体，所述蛋白质构建体包含与选自下组的序列至少80％，至少约85％，至少约90％，至少约95％，至少约97％或至少约99％相同的氨基酸序列：SEQ ID NO:107,SEQ ID NO:110,SEQ ID NO:113,SEQ ID NO:116,SEQ ID NO:119,SEQ ID NO:122,SEQ ID NO:125,SEQ ID NO:128,SEQ ID NO:131,SEQID NO:161,SEQ ID NO:167,SEQ ID NO:173,SEQ ID NO:179,SEQ ID NO:185,SEQ ID NO:191,SEQ ID NO:200,SEQ ID NO:206,SEQ ID NO:212,SEQ ID NO:215,SEQ ID NO:220,SEQID NO:223,SEQ ID NO:225,SEQ ID NO:227,SEQ ID NO:229,SEQ ID NO:231,SEQ ID NO:233,SEQ ID NO:238,SEQ ID NO:241,SEQ ID NO:243,SEQ ID NO:245,SEQ ID NO:247,SEQID NO:249,SEQ ID NO:251,SEQ ID NO:253,SEQ ID NO:255,SEQQ ID NO:257,SEQ ID NO:259,SEQ ID NO:264,SEQ ID NO:271,SEQ ID NO:278,SEQ ID NO:285,SEQ ID NO:292,SEQID NO:299,SEQ ID NO:306,SEQ ID NO:313,SEQ ID NO:320,SEQ ID NO:327,SEQ ID NO:334,SEQ ID NO:341,SEQ ID NO:348,SEQ ID NO:355,SEQ ID NO:362,SEQ ID NO:369,SEQID NO:376,SEQ ID NO:383,SEQ ID NO:390和SEQ ID NO:397，其中蛋白质构建体能够选择性结合抗流感抗体。在本发明的一个实施方案中，纳米颗粒包含蛋白质构建体，所述蛋白质构建体包含选自下组的氨基酸序列：SEQ ID NO:107,SEQ ID NO:110,SEQ ID NO:113,SEQID NO:116,SEQ ID NO:119,SEQ ID NO:122,SEQ ID NO:125,SEQ ID NO:128,SEQ ID NO:131,SEQ ID NO:161,SEQ ID NO:167,SEQ ID NO:173,SEQ ID NO:179,SEQ ID NO:185,SEQID NO:191,SEQ ID NO:200,SEQ ID NO:206,SEQ ID NO:212,SEQ ID NO:215,SEQ ID NO:220,SEQ ID NO:223,SEQ ID NO:225,SEQ ID NO:227,SEQ ID NO:229,SEQ ID NO:231,SEQID NO:233,SEQ ID NO:238,SEQ ID NO:241,SEQ ID NO:243,SEQ ID NO:245,SEQ ID NO:247,SEQ ID NO:249,SEQ ID NO:251,SEQ ID NO:253,SEQ ID NO:255,SEQQ ID NO:257,SEQ ID NO:259,SEQ ID NO:264,SEQ ID NO:271,SEQ ID NO:278,SEQ ID NO:285,SEQ IDNO:292,SEQ ID NO:299,SEQ ID NO:306,SEQ ID NO:313,SEQ ID NO:320,SEQ ID NO:327,SEQ ID NO:334,SEQ ID NO:341,SEQ ID NO:348,SEQ ID NO:355,SEQ ID NO:362,SEQ IDNO:369,SEQ ID NO:376,SEQ ID NO:383,SEQ ID NO:390和SEQ ID NO:397。
在一个实施方案中，本发明的纳米颗粒包含由核酸分子编码的蛋白质构建体，所述核酸分子包含与选自下组的序列至少85％,至少90％,至少95％or至少97％相同的核酸序列：SEQ ID NO:266,SEQ ID NO:273,SEQ ID NO:SEQ ID NO:280,SEQ ID NO:287,SEQ IDNO:294,SEQ ID NO:301,SEQ ID NO:308,SEQ ID NO:315,SEQ ID NO:322,SEQ ID NO:329,SEQ ID NO:336,SEQ ID NO:343,SEQ ID NO:350,SEQ ID NO:357,SEQ ID NO:364,SEQ IDNO:371,SEQ ID NO:378,SEQ ID NO:385SEQ ID NO:392和SEQ ID NO:399。在一个实施方案中，本发明的纳米颗粒包含由核酸分子编码的蛋白质构建体，所述核酸分子包含选自下组的核酸序列：SEQ ID NO:266,SEQ ID NO:273,SEQ ID NO:SEQ ID NO:280,SEQ ID NO:287,SEQ ID NO:294,SEQ ID NO:301,SEQ ID NO:308,SEQ ID NO:315,SEQ ID NO:322,SEQ IDNO:329,SEQ ID NO:336,SEQ ID NO:343,SEQ ID NO:350,SEQ ID NO:357,SEQ ID NO:364,SEQ ID NO:371,SEQ ID NO:378,SEQ ID NO:385SEQ ID NO:392和SEQ ID NO:399。
本发明的纳米颗粒可用于引发对流感病毒的免疫应答。一类免疫应答是B细胞应答，其导致产生针对引发免疫应答的抗原的抗体。因此，在一个实施方案中，纳米颗粒引发结合来自选自A型流感病毒，B型流感病毒和C型流感病毒的病毒的流感HA蛋白的茎区的抗体。本发明的一个实施方案是纳米颗粒，其引发结合流感HA蛋白的茎区的抗体，所述流感HA蛋白选自H1流感病毒HA蛋白，H2流感病毒HA蛋白，H3流感病毒HA蛋白，H4流感病毒HA蛋白，H5流感病毒HA蛋白，H6流感病毒HA蛋白，H7流感病毒HA蛋白，H8流感病毒HA蛋白，H9流感病毒HA蛋白，H10流感病毒HA蛋白HA蛋白，H11流感病毒HA蛋白，H12流感病毒HA蛋白，H13流感病毒HA蛋白，H14流感病毒HA蛋白，H15流感病毒HA蛋白，H16流感病毒HA蛋白，H17流感病毒HA蛋白，和H18流感病毒HA蛋白。本发明的一个实施方案是纳米颗粒，其引发结合来自病毒株的流感HA蛋白的茎区的抗体，所述病毒株选自流感A/新喀里多尼亚/20/1999(1999NC,H1),A/加利福尼亚/04/2009(2009CA,H1),A/新加坡/1/1957(1957Sing,H2),A/香港/1/1968(1968HK,H3),A/布里斯班/10/2007(2007Bris,H3),A/印度尼西亚/05/2005(2005Indo,H5),B/佛罗里达/4/2006(2006Flo,B),A/珀斯/16/2009(2009Per,H3),A/布里斯班/59/2007(2007Bris,H1),B/布里斯班/60/2008(2008Bris,B)及其变体。
尽管所有抗体能够结合引发导致抗体产生的免疫应答的抗原，但优选的抗体是那些提供针对流感病毒的广泛的异亚型保护的抗体。因此，本发明的一个实施方案是引发保护性抗体的纳米颗粒，所述保护性抗体结合来自选自A型流感病毒，B型流感病毒和C型流感病毒的病毒的流感HA蛋白的茎区。本发明的一个实施方案是引发与流感HA蛋白的茎区结合的保护性抗体的蛋白质，所述流感HA蛋白选自H1流感病毒HA蛋白，H2流感病毒HA蛋白，H3流感病毒HA蛋白，H4流感病毒HA蛋白，H5流感病毒HA蛋白，H6流感病毒HA蛋白，H7流感病毒HA蛋白，H8流感病毒HA蛋白，H9流感病毒HA蛋白，H10流感病毒HA蛋白HA蛋白，H11流感病毒HA蛋白，H12流感病毒HA蛋白，H13流感病毒HA蛋白，H14流感病毒HA蛋白，H15流感病毒HA蛋白，H16流感病毒HA蛋白，H17流感病毒HA蛋白，和H18流感病毒HA蛋白。本发明的一个实施方案是引发针对选自下组的病毒的抗体的纳米颗粒：流感A/新喀里多尼亚/20/1999(1999NC,H1),A/加利福尼亚/04/2009(2009CA,H1),A/新加坡/1/1957(1957Sing,H2),A/香港/1/1968(1968HK,H3),A/布里斯班/10/2007(2007Bris,H3),A/印度尼西亚/05/2005(2005Indo,H5),B/佛罗里达/4/2006(2006Flo,B),A/珀斯/16/2009(2009Per,H3),A/布里斯班/59/2007(2007Bris,H1)and B/布里斯班/60/2008(2008Bris,B)。本发明的一个实施方案是引发结合蛋白质的抗体的纳米颗粒，所述蛋白质包含与选自下组的序列至少80％相同的氨基酸序列：SEQ ID NO:8,SEQ ID NO:11,SEQ ID NO:14和SEQ ID NO:17。本发明的一个实施方案是引发结合蛋白质的抗体的纳米颗粒，所述蛋白质包含选自SEQ ID NO:8，SEQID NO:11，SEQ ID NO:14和SEQ ID NO:17的氨基酸序列。
由本发明的蛋白质引发的保护性抗体可通过影响病毒生命周期中的任何步骤来提供保护免受病毒感染。例如，保护性抗体可以防止流感病毒附着于细胞，进入细胞，将病毒核糖核蛋白释放到细胞质中，在受感染的细胞中形成新的病毒颗粒并从受感染的宿主细胞膜出芽新的病毒颗粒。在一个实施方案中，由本发明的蛋白质引发的保护性抗体防止流感病毒进入宿主细胞。在一个实施方案中，由本发明的蛋白质引发的保护性抗体防止病毒膜与内体膜的融合。在一个实施方案中，由本发明的蛋白质引发的保护性抗体防止核糖核蛋白释放到宿主细胞的细胞质中。在一个实施方案中，由本发明的蛋白质引发的保护性抗体防止新病毒在感染的宿主细胞中的装配。在一个实施方案中，由本发明的蛋白质引发的保护性抗体防止新形成的病毒从感染的宿主细胞释放。
因为流感病毒的茎区的氨基酸序列是高度保守的，所以由本发明的纳米颗粒引发的保护性抗体可以是广泛保护性的。也就是说，本发明的纳米颗粒引发的保护性抗体可以针对多于一种类型，亚型和/或毒株的流感病毒提供保护。因此，本发明的一个实施方案是引发结合流感HA蛋白茎区的广泛保护性抗体的蛋白质。一个实施方案是引发结合来自多于一种类型的流感病毒的HA蛋白的茎区的抗体的纳米颗粒，所述流感病毒选自A型流感病毒，B型流感病毒和C型流感病毒。一个实施方案是引发结合来自多于一种亚型流感病毒的HA蛋白的茎区的抗体的纳米颗粒，所述流感病毒选自H1流感病毒，H2流感病毒，H3流感病毒，H4流感病毒，H5流感病毒，H6流感病毒，H7流感病毒，H8流感病毒，H9流感病毒，H10流感病毒，H11流感病毒，H12流感病毒，H13流感病毒，H14流感病毒，H15流感病毒，H16流感病毒，H17流感病毒和H18流感病毒。一个实施方案是引发结合来自超过流感病毒株的HA蛋白的茎区的抗体的纳米颗粒。本发明的一个实施方案是引发结合超过一种蛋白质的抗体的纳米颗粒，所述蛋白质包含与选自下组的序列至少80％相同的氨基酸序列：SEQ ID NO:8,SEQ ID NO:11,SEQ ID NO:14和SEQ ID NO:17。本发明的一个实施方案是引发结合多于一种蛋白质的抗体的纳米颗粒，所述蛋白质包含选自SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQID NO:17的氨基酸序列。
因为本发明的纳米颗粒可以引发对流感病毒的免疫应答，所以它们可用作保护个体免受流感病毒感染的疫苗。因此，本发明的一个实施方案是包含本发明的纳米颗粒的疫苗。本发明的疫苗还可以含有其它成分，如佐剂，缓冲液等。尽管可以使用任何佐剂，但优选的实施方案可以含有：化学佐剂，如磷酸铝，benzyalkonium chloride，乌苯美司(ubenimex)和QS21；遗传佐剂如IL-2基因或其片段，粒细胞巨噬细胞集落刺激因子(GM-CSF)基因或其片段，IL-18基因或其片段，趋化因子(CC基序)配体21(CCL21)基因或其片段，IL-6基因或其片段，CpG，LPS，TLR激动剂和其它免疫刺激基因；蛋白质佐剂如IL-2或其片段，粒细胞巨噬细胞集落刺激因子(GM-CSF)或其片段，IL-18或其片段，趋化因子(CC基序)配体21(CCL21)或其片段，IL-6或其片段，CpG，LPS，TLR激动剂和其它免疫刺激性细胞因子或其片段；脂质佐剂如阳离子脂质体，N3(阳离子脂质)，单磷酰脂质A(MPL1)；其它佐剂，包括霍乱毒素，肠毒素，Fms样酪氨酸激酶-3配体(Flt-3L)，布比卡因(bupivacaine)，丁哌卡因(marcaine)和左旋咪唑。
本发明的一个实施方案是包含多于一种流感HA蛋白的纳米颗粒疫苗。此类疫苗可以包括在单个纳米颗粒上或作为纳米颗粒混合物的不同流感HA蛋白的组合，其中至少两种具有独特的流感HA蛋白。多价疫苗可包含与必要一样多的流感HA蛋白，以便导致提供保护免于期望的病毒毒株宽度必需的免疫应答的产生。在一个实施方案中，疫苗包含来自至少两种不同流感株(二价)的HA蛋白。在一个实施方案中，疫苗包含来自至少三种不同流感株(三价)的HA蛋白。在一个实施方案中，疫苗包含来自至少四种不同流感株(四价)的HA蛋白。在一个实施方案中，疫苗包含来自至少五种不同流感株(五价)的HA蛋白。在一个实施方案中，疫苗包含来自至少六种不同流感病毒株(六价)的HA蛋白。在各种实施方案中，疫苗包含来自7、8、9或10种不同流感病毒株之每种的HA蛋白。此类组合的实例是包含流感A组1HA蛋白，流感A组2HA蛋白，和流感B HA蛋白的纳米颗粒疫苗。在一个实施方案中，流感HA蛋白是H1HA，H3HA和B HA。在一个实施方案中，流感HA蛋白是包括在2011-2012流感疫苗中的那些。多价疫苗的另一个实例是包含来自四种不同流感病毒的HA蛋白的纳米颗粒疫苗。在一个实施方案中，多价疫苗包含来自流感A/新喀里多尼亚/20/1999(1999NC,H1),A/加利福尼亚/04/2009(2009CA,H1),A/新加坡/1/1957(1957Sing,H2),A/香港/1/1968(1968HK,H3),A/布里斯班/10/2007(2007Bris,H3),A/印度尼西亚/05/2005(2005Indo,H5),B/佛罗里达/4/2006(2006Flo,B),A/珀斯/16/2009(2009Per,H3),A/布里斯班/59/2007(2007Bris,H1)和B/布里斯班/60/2008(2008Bris,B)的HA蛋白。
本发明的一个实施方案是针对流感病毒对个体接种疫苗的方法，所述方法包括向个体施用纳米颗粒，使得在个体中产生针对流感病毒的免疫应答，其中所述纳米颗粒包含连接到流感HA蛋白的单体亚基蛋白，并且其中所述纳米颗粒在其表面上展示所述流感HA。在一个实施方案中，纳米颗粒是单价纳米颗粒。在一个实施方案中，纳米颗粒是多价纳米颗粒。本发明的另一个实施方案是针对流感病毒感染对个体接种疫苗的方法，所述方法包括：
a)获得包含单体亚基的纳米颗粒，其中所述单体亚基与流感血凝素蛋白连接，并且其中所述纳米颗粒在其表面上展示流感HA；并且，
b)将纳米颗粒施用于个体，使得产生针对流感病毒的免疫应答。
本发明的一个实施方案是针对流感病毒对个体接种疫苗的方法，所述方法包括向个体施用实施方案的疫苗，使得在个体中产生针对流感病毒的免疫应答，其中所述疫苗包含至少一种纳米颗粒，其包含与流感HA蛋白连接的单体亚基，并且其中所述纳米颗粒在其表面上展示流感HA。在一个实施方案中，疫苗是单价疫苗。在一个实施方案中，疫苗是多价疫苗。本发明的另一个实施方案是针对流感病毒感染对个体接种疫苗的方法，所述方法包括：
a)获得包含至少一种包含本发明的蛋白质构建体的纳米颗粒的疫苗，其中所述蛋白质构建体包含与流感HA蛋白连接的单体亚基蛋白，并且其中所述纳米颗粒在其表面上展示流感HA；并且，
b)将所述疫苗施用于个体，使得产生针对流感病毒的免疫应答。
在一个实施方案中，纳米颗粒是单价纳米颗粒。在一个实施方案中，纳米颗粒是多价纳米颗粒。
在一个实施方案中，纳米颗粒具有八面体对称。在一个实施方案中，流感HA蛋白能够引发针对流感病毒的抗体。在一个实施方案中，流感HA蛋白能够广泛引发针对流感病毒的抗体。在优选的实施方案中，引发的抗体是保护性抗体。在优选的实施方案中，引发的抗体是广泛异亚型保护性的。
本发明的疫苗可用于使用初免/加强方案对个体接种疫苗。此类方案在美国专利公开号20110177122中描述，其通过引用整体并入本文。在此类方案中，可以向个体施用第一疫苗组合物(初次)，然后在一段时间后，可以向个体施用第二疫苗组合物(加强)。施用加强组合物通常是在施用引发组合物后数周或数月，优选约2-3周或4周，或8周，或16周，或20周，或24周，或28周，或32周。在一个实施方案中，配制加强组合物，用于在施用引发组合物后约1周，或2周，或3周，或4周，或5周，或6周，或7周，或8周，或9周，或16周，或20周，或24周，或28周，或32周施用。
第一和第二疫苗组合物可以是，但不需要是相同的组合物。因此，在本发明的一个实施方案中，施用疫苗的步骤包括施用第一疫苗组合物，然后在稍后时间施用第二疫苗组合物。在一个实施方案中，第一疫苗组合物包含本发明的纳米颗粒。在一个实施方案中，第一疫苗组合物包含纳米颗粒，其包含来自流感病毒的HA蛋白的氨基酸序列，所述流感病毒选自A/新喀里多尼亚/20/1999(1999NC,H1),A/加利福尼亚/04/2009(2009CA,H1),A/新加坡/1/1957(1957Sing,H2),A/香港/1/1968(1968HK,H3),A/布里斯班/10/2007(2007Bris,H3),A/印度尼西亚/05/2005(2005Indo,H5),B/佛罗里达/4/2006(2006Flo,B),A/珀斯/16/2009(2009Per,H3),A/布里斯班/59/2007(2007Bris,H1),B/布里斯班/60/2008(2008Bris,B)。
在一个实施方案中，接种疫苗的个体已暴露于流感病毒。如本文所使用的，术语暴露的，暴露等指示受试者已经与已知感染流感病毒的动物对象接触。可以使用本领域技术人员熟知的技术来施用本发明的疫苗。用于配制和施用的技术可以在例如“Remington’sPharmaceutical Sciences”,18th ed.,1990,Mack Publishing Co.,Easton,PA中找到。疫苗可通过包括但不限于传统注射器，无针注射装置或微粒轰击基因枪的手段施用。合适的施用途径包括但不限于肠胃外递送，如肌内，皮内，皮下，髓内注射以及鞘内，直接心室内，静脉内，腹膜内，鼻内或眼内注射，仅举几个例子。对于注射，本发明的一个实施方案的化合物可以配制在水溶液中，优选在生理上相容的缓冲液如Hanks溶液，林格氏溶液或生理盐水缓冲液中配制。
在一个实施方案中，本发明的疫苗或纳米颗粒可用于保护个体免受异源流感病毒的感染。也就是说，使用来自流感病毒的一种毒株的HA蛋白制备的疫苗能够保护个体免受不同流感病毒株的感染。例如，使用来自流感A/新喀里多尼亚/20/1999(1999NC,H1)的HA蛋白制备的疫苗可以用于保护个体免受流感病毒感染，所述流感病毒包括但不限于A/新喀里多尼亚/20/1999(1999NC,H1),A/加利福尼亚/04/2009(2009CA,H1),A/新加坡/1/1957(1957Sing,H2),A/香港/1/1968(1968HK,H3),A/布里斯班/10/2007(2007Bris,H3),A/印度尼西亚/05/2005(2005indo,H5),A/珀斯/16/2009(2009Per,H3),和/或A/布里斯班/59/2007(2007Bris,H1)。
在一个实施方案中，本发明的疫苗或纳米颗粒可用于保护个体免于抗原性趋异的流感病毒的感染。抗原性趋异的是指流感病毒株随时间突变的趋势，从而改变展示给免疫系统的氨基酸。此类随时间的突变也称为抗原漂移。因此，例如，使用来自A/新喀里多尼亚/20/1999(1999NC,H1)流感病毒株的HA蛋白制备的疫苗能够保护个体免受早期的，抗原性趋异的新喀里多尼亚流感毒株的感染，和未来的进化(或趋异)流感毒株。
因为本发明的纳米颗粒展示与完整HA在抗原性上相似的HA蛋白，所以它们可用于检测针对流感病毒的抗体(抗流感抗体)的测定法中。
因此，本发明的一个实施方案是使用本发明的纳米颗粒检测抗流感病毒抗体的方法。本发明的检测方法通常可以通过以下步骤实现：
a.使测试抗流感抗体的存在的样品的至少部分与本发明的纳米颗粒接触；并且，
b.检测纳米颗粒/抗体复合物的存在；
其中纳米颗粒/抗体复合物的存在指示样品含有抗流感抗体。
在本发明的一个实施方案中，从待测试抗流感病毒抗体的存在的个体获得或收集样品。个体可以是或不是怀疑具有抗流感抗体或已经暴露于流感病毒的。样品是从个体获得的任何样本，其可用于测试抗流感病毒抗体的存在。优选的样品是可用于检测抗流感病毒抗体的存在的体液。可用于实施本发明方法的体液的实例包括但不限于血液，血浆，血清，泪液和唾液。本领域技术人员可以容易地鉴定适于实施所公开的方法的样品。
血液或血液衍生的液体如血浆，血清等特别适合作为样品。可以使用本领域已知的方法从个体收集和制备此类样品。样品可以在测定前冷藏或冷冻。
本发明的任何纳米颗粒可用于实施所公开的方法，只要纳米颗粒结合抗流感病毒抗体。有用的纳米颗粒及其制备方法已在本文中详细描述。在优选的实施方案中，纳米颗粒包含蛋白质构建体，其中蛋白质构建体包含连接到(融合到)来自流感HA蛋白的至少一个表位的来自单体亚基蛋白的至少25个，至少50个，至少75个，至少100个或至少150个连续氨基酸，使得纳米颗粒在其表面上包含流感病毒HA蛋白表位的三聚体，并且其中蛋白质构建体能够自组装成纳米颗粒。
如本文中使用的，术语接触是指将测试抗流感抗体存在的样品引入本发明的纳米颗粒，例如通过组合或混合样品和本发明的纳米颗粒，使得纳米颗粒能够与样品中的抗体(如果存在的话)物理接触。当抗流感病毒抗体存在于样品中时，然后形成抗体/纳米颗粒复合物。此类复合物形成是指抗流感病毒抗体选择性结合纳米颗粒中蛋白质构建体的HA部分以形成可检测的稳定复合物的能力。样品中抗流感病毒抗体与纳米颗粒的结合在适合形成复合物的条件下完成。此类条件(例如，适当的浓度，缓冲液，温度，反应时间)以及优化此类条件的方法是本领域技术人员已知的。结合可以使用本领域标准的多种方法测量，包括但不限于凝集测定法，沉淀测定法，酶免疫测定法(例如ELISA)，免疫沉淀测定法，免疫印迹测定法和其它免疫测定法，如例如记载于Sambrook et al.,Molecular Cloning:ALaboratory Manual,(Cold Spring Harbor Labs Press,1989)和Harlow et al.,Antibodies,a Laboratory Manual(Cold Spring Harbor Labs Press,1988)，两者均通过引用整体并入本文。这些参考文献还提供了复合物形成条件的实例。
如本文所使用的，短语选择性地结合HA，选择性结合HA等，是指与结合与HA无关的蛋白质，或样品或测定法中的非蛋白质组分形成对比，抗体优先结合HA蛋白的能力。选择性结合HA的抗体是结合HA但不显著结合可能存在于样品或测定法中的其它分子或组分的抗体。显著的结合被认为是例如抗HA抗体与非HA分子的结合，以大到足以干扰测定法检测和/或测定样品中的抗流感抗体的水平的能力的亲和力或亲合力。可存在于样品或测定法中的其它分子和化合物的实例包括但不限于非HA蛋白，例如白蛋白，脂质和碳水化合物。
在一个实施方案中，可以在溶液中形成抗流感病毒抗体/纳米颗粒复合物(本文中也称为抗体/纳米颗粒复合物)。在一个实施方案中，可以形成抗体/纳米颗粒复合物，其中纳米颗粒固定在(例如，涂覆到)基底上。固定化技术是本领域技术人员已知的。合适的基底材料包括但不限于塑料，玻璃，凝胶，赛璐珞(celluloid)，织物，纸和颗粒材料。基底材料的实例包括但不限于胶乳，聚苯乙烯，尼龙，硝化纤维素，琼脂糖，棉，PVDF(聚偏氟乙烯)和磁性树脂。用于基底材料的合适形状包括但不限于孔(例如，微量滴定盘孔)，微量滴定板，浸渍片，条，珠，侧流装置，膜，过滤器，管，盘，赛璐珞型基质，磁性颗粒和其它颗粒。特别优选的底物包括例如ELISA板，浸渍片，免疫斑点条，放射免疫测定板，琼脂糖珠，塑料珠，乳胶珠，棉线，塑料芯片，免疫印迹膜，免疫印迹纸和流通膜。在一个实施方案中，基底，如颗粒，可以包括可检测标记物。对于基底材料的实例的描述，参见例如Kemeny,D.M.(1991)APractical Guide to ELISA,Pergamon Press,Elmsford,NY pp 33-44,以及Price,C.andNewman,D.eds.Principles and Practice of Immunoassay,2nd edition(1997)StocktonPress,NY,NY，两者通过引用整体并入本文。
根据本发明，一旦形成，就检测抗流感病毒抗体/纳米颗粒复合物。检测可以是定性，定量或半定量的。如本文所使用的，短语检测复合物形成，检测复合物等是指鉴定与纳米颗粒复合的抗流感病毒抗体的存在。如果形成复合物，则可以但不需要量化形成的复合物的量。假定的抗流感病毒抗体和纳米颗粒之间的复合物形成或选择性结合可以使用本领域标准的多种方法测量(即检测，测定)(参见例如Sambrook等人，同上)，其实例在本文中公开。可以以多种方式检测复合物，包括但不限于使用一种或多种下列测定法：血凝抑制测定法，径向扩散测定法，酶联免疫测定法，竞争性酶联免疫测定法，放射免疫测定法，荧光免疫测定法，化学发光测定法，侧向流测定法，流通测定法，基于颗粒的测定法(例如，使用颗粒，如但不限于磁性颗粒或塑料聚合物，如胶乳或聚苯乙烯珠)，免疫沉淀测定法，BioCoreJ测定法(例如，使用胶体金)，免疫斑点测定法(例如，CMG＝s免疫印迹系统(s ImmunodotSystem)，Friborg，Switzerland)和免疫印迹测定法(例如，western印迹)，磷光测定法，流通测定法，层析测定法，基于PAGe的测定，表面等离振子共振测定法，分光光度测定法和电子感觉测定。此类测定法是本领域技术人员公知的。
测定法可用于根据其使用方式给出定性或定量结果。可以通过目视(例如，通过眼或通过机器，如密度计或分光光度计)观察到一些测定法，如凝集，颗粒分离和沉淀测定法，而不需要可检测的标记物。
在其它测定法中，可检测标记物与纳米颗粒或与选择性结合纳米颗粒的试剂的缀合(即，附着)有助于检测复合物形成。可检测标记物可以在不干扰纳米颗粒结合抗流感病毒抗体的能力的位点与纳米颗粒或纳米颗粒结合试剂缀合。缀合方法是本领域技术人员已知的。可检测标记物的实例包括但不限于放射性标记物，荧光标记物，化学发光标记物，发色标记物，酶标记物，磷光标记物，电子标记物；金属溶胶标记物，有色珠，物理标记物或配体。配体是指与另一分子选择性结合的分子。优选的可检测标记物包括但不限于荧光素，放射性同位素，磷酸酶(例如碱性磷酸酶)，生物素，抗生物素蛋白，过氧化物酶(例如辣根过氧化物酶)，β-半乳糖苷酶和生物素相关化合物或抗生物素蛋白相关化合物(例如链霉抗生物素蛋白或ImmunoPure7NeutrAvidin)。
在一个实施方案中，可以通过使样品与结合抗流感抗体，铁蛋白或与抗体/纳米颗粒复合物的特异性化合物(如抗体)接触来检测抗体/纳米颗粒复合物，所述特异性化合物与可检测标记物缀合。可检测标记物可以以不阻断化合物结合所检测的复合物的能力的方式与特定化合物缀合。优选的可检测标记物包括但不限于荧光素，放射性同位素，磷酸酶(例如碱性磷酸酶)，生物素，抗生物素蛋白，过氧化物酶(例如辣根过氧化物酶)，β-半乳糖苷酶和生物素相关化合物或抗生物素蛋白相关化合物(例如链霉抗生物素蛋白或ImmunoPure7NeutrAvidin)。
在另一个实施方案中，通过使复合物与指示剂分子接触来检测复合物。合适的指示剂分子包括可以结合抗流感病毒抗体/纳米颗粒复合物，抗流感病毒抗体或纳米颗粒的分子。因此，指示剂分子可以包括例如结合抗流感病毒抗体的试剂，如识别免疫球蛋白的抗体。作为抗体的优选指示剂分子包括例如与来自其中产生抗流感病毒抗体的个体物种的抗体反应的抗体。指示剂分子本身可以附着到本发明的可检测标志物。例如，抗体可以与生物素，辣根过氧化物酶，碱性磷酸酶或荧光素缀合。
本发明还可以包含能够检测指示剂分子存在的二级分子或其它结合分子的一个或多个层和/或类型。例如，选择性结合指示剂分子的无标签的(即，不与可检测标志物缀合的)二抗可以与选择性结合二抗的有标签的(即，与可检测标志物缀合的)三抗结合。合适的二抗，三抗和其它二级或三级分子可以容易地由本领域技术人员选择。优选的三级分子也可以由本领域技术人员基于第二分子的特性来选择。相同的策略可以应用于后续层。
优选地，指示剂分子与可检测标志物缀合。如果需要的话，加入显影剂，并将底物送到检测装置进行分析。在一些方案中，在一个或两个复合物形成步骤之后加入清洗步骤以除去过量的试剂。如果使用这些步骤，则它们牵涉本领域技术人员已知的条件，使得除去过量的试剂，但保留复合物。
因为本发明的测定法可以检测样品(包括血液样品)中的抗流感病毒抗体，所以此类测定法可用于鉴定具有抗流感抗体的个体。因此，本发明的一个实施方案是鉴定具有抗流感病毒抗体的个体的方法，所述方法包括：
a.使来自测试抗流感抗体的个体的样品与本发明的纳米颗粒接触；和，
b.分析接触的样品的纳米颗粒/抗体复合物的存在，
其中纳米颗粒/抗体复合物的存在指示所述个体具有抗流感抗体。
任何公开的测定形式可用于进行所公开的方法。有用的测定形式的实例包括但不限于径向扩散测定法，酶联免疫测定法，竞争性酶联免疫测定法，放射免疫测定法，荧光免疫测定法，化学发光测定法，侧向流测定法，通过测定法，基于颗粒的测定法(例如，使用颗粒，如但不限于磁性颗粒或塑料聚合物，如胶乳或聚苯乙烯珠)，免疫沉淀测定法，BioCoreJ测定(例如，使用胶体金)，免疫印迹测定法(例如，CMG＝s免疫印迹系统，Fribourg，Switzerland)和免疫印迹测定法(例如，western印迹)，磷光测定法，流通测定法，层析测定法，基于PAGe的测定法，表面等离振子共振测定法，生物层干涉测定法，分光光度测定法和电子感觉测定法。
如果在样品中没有检测到抗流感抗体，则此类结果指示个体不具有抗流感病毒抗体。测试的个体可以是或不是怀疑具有针对流感病毒的抗体的。所公开的方法还可以用于确定个体是否已经暴露于流感病毒的一种或多种特定类型，组，亚组或毒株。为了进行此类测定，从个体获得样品，所述个体在其过去(例如，大于约1年，大于约2年，大于约3年，大于约4年，大于约5年等)的某个时候在针对流感病毒的一种或多种特定类型，组，亚组或毒株的抗体测试呈阴性(即，缺少抗体)。然后使用本发明的基于纳米颗粒的测定法测试样品的针对流感病毒的一种或多种类型，组，亚组或毒株的抗流感病毒抗体的存在。如果测定法指示存在此类抗体，则在鉴定它们为抗流感抗体阴性的测试后的某个时候将个体鉴定为已经暴露于流感病毒的一种或多种类型，组亚组或毒株。因此，本发明的一个实施方案是鉴定已暴露于流感病毒的个体的方法，所述方法包括：
a.使来自正在测试抗流感抗体的个体的样品的至少部分与本发明的纳米颗粒接触；和，
b.分析接触的样品的抗体/纳米颗粒复合物的存在或水平，其中抗体/纳米颗粒复合物的存在或水平指示最近的抗流感抗体的存在或水平；
c.将最近的抗流感抗体水平与过去的抗流感抗体水平进行比较；
其中最近的抗流感抗体水平相对于过去的抗流感抗体水平的增加指示个体在确定过去的抗流感抗体水平之后已经暴露于流感病毒。
本发明的方法还可用于确定个体对疫苗的响应。因此，一个实施方案是用于测量个体对流感疫苗的响应的方法，所述方法包括：
a.向个体施用流感病毒疫苗；
b.使来自所述个体的样品的至少部分与本发明的纳米颗粒接触；
c.分析接触的样品的抗体/纳米颗粒复合物的存在或水平，其中抗体/纳米颗粒复合物的存在或水平指示最近的抗流感抗体的存在或水平
其中所述样品中抗体的水平相对于所述个体中抗体的疫苗接种前水平的增加指示疫苗在所述个体中诱导免疫应答。
施用于个体的流感疫苗可以但不需要包含本发明的疫苗，只要纳米颗粒包含可以结合由施用的疫苗诱导的抗流感抗体的HA蛋白。施用流感疫苗的方法是本领域技术人员已知的。
可以使用任何公开的测定形式进行对从个体获得的样品的分析。在一个实施方案中，使用选自以下的测定形式进行样品的分析：径向扩散测定法，酶联免疫测定法，竞争性酶联免疫测定法，放射免疫测定法，荧光免疫测定法，化学发光测定法，侧向流测定法，流通测定法，基于颗粒的测定法(例如，使用颗粒，如但不限于磁性颗粒或塑料聚合物，如胶乳或聚苯乙烯珠)，免疫沉淀测定法，BioCoreJ测定法(例如，使用胶体金)，免疫斑点测定法(例如，CMG＝s免疫印迹系统，Fribourg，Switzerland)和免疫印迹测定法(例如，western印迹)，磷光测定法，流通测定法，层析测定法，基于PAGE的测定法，表面等离振子共振测定法，生物层干涉测定测定法，分光光度测定法和电子感觉测定法。
在一个实施方案中，所述方法包括在施用疫苗之前测定个体中存在的抗流感抗体的水平的步骤。然而，如果此类信息可用，则也可以从先前的医学记录确定个体中存在的抗流感抗体的水平。
虽然不必实施所公开的方法，但优选在施用疫苗的步骤和确定个体中抗流感抗体的水平的步骤之间等待一段时间。在一个实施方案中，对个体中存在的抗流感抗体的水平的测定在使用疫苗后的至少1天，至少2天，至少3天，至少4天，至少5天，至少6天，至少1周，至少2周，至少3周，至少4周，至少2个月，至少3个月或至少6个月实施。
本发明还包括适用于检测抗流感抗体的试剂盒。合适的检测手段包括利用本发明的纳米颗粒的本文公开的技术。试剂盒还可以包含可检测标志物，如选择性结合纳米颗粒的抗体或其它指示剂分子的抗体。试剂盒还可以包含相关联的组分，如但不限于缓冲液，标记物，容器，插页，管，小瓶，注射器等。
实施例
提出以下实施例以便向本领域普通技术人员提供如何制备和使用实施方案的完整公开和描述，并且不旨在限制发明人认为是其发明的范围，它们也不意图表示下面的实验是所进行的全部或唯一的实验。已经做出努力以确保关于使用的数字(例如量，温度等)的准确性，但是应该考虑一些实验误差和偏差。除非另有指示，份数是重量份，分子量是重量平均分子量，并且温度以摄氏度计。使用标准缩写。
实施例1：HA稳定化茎(HA-SS)构建体的基于结构的迭代设计
该实施例显示用于产生缺乏免疫显性头部结构域的HA稳定化茎(HA-SS)免疫原的基于结构的设计的六个迭代循环(Gen1-Gen6)。
流感A病毒包含18种HA亚型，其中两种H1和H3目前导致大多数人类感染。季节性流感疫苗针对循环H1和H3株提供了一些保护，但很少提供针对趋异的H5，H7和H9亚型的保护，其导致人类感染的偶然暴发，作为来自禽类和/或猪库的人畜共患病。本发明人假设聚焦于保守血凝素(HA)茎的免疫应答可能潜在地引发针对多种多样毒株的广泛的异亚型流感保护。因此，本发明人使用基于结构的迭代设计来开发缺乏免疫显性HA头部区的HA稳定化茎(HA-SS)糖蛋白(图1)。
A/新喀里多尼亚/20/1999(1999NC)HA的胞外域序列和A/南卡罗来纳/1/1918(1918SC)的晶体结构(PDB ID 1GBN)用作设计模板，并且对每代HA-SS变体评估作为可溶性三聚体的表达，以及基于与野生型(wt)HA三聚体相似的茎特异性单克隆抗体(mAb)反应性评估抗原性。
使用人优选密码子合成编码来自1999NC，1986SG，2009CA，H2 2005CAN，H52005IND和H5 2004VN的全长HA和神经氨酸酶(NA)的质粒。通过重叠PCR和定点诱变产生不同形式的HA-SS。在freestyle 293(293F；Life Technologies)细胞或293GnTI-/-细胞(用于Gen4HA-SS结晶)中表达所有HA，HA-SS蛋白和mAb，并如前所述进行纯化(Wei,C.J.,etal.Elicitation of broadly neutralizing influenza antibodies in animals withprevious influenza exposure.Sci.Transl.Med.4,147ra114(2012))。如所述(Kanekiyo,M.,et al.Nature 499,102-106(2013))进行HA-np和Gen1-Gen6HA-SS和Gen4-6HA-SS-np的构建，纯化和表征。
第一代设计(Gen1HA-SS)用GSG接头替换受体结合结构域(残基HA1 51-277，H3编号)(图1)。各自产生HA胞外域三聚体和所有三聚体HA-SS设计，C-末端跨膜和胞质残基HA2175-220(H3编号)替换为短接头，T4折叠物，凝血酶切割位点和His标签。使HA1/HA2切割位点突变以防止切割。为了模拟HA-SS设计的结构，使用1918SC HA(PDB ID 1GBN)和噬菌体T4折叠物三聚体(PDB ID 1RFO)作为模板，使用LOOPY(Xiang,et.al.Proc.Natl.Acad.Sci.U.S.A.99,7432-7437(2002))设计环和连接，使用SCAP(Xiang,et al.,J.Mol.Biol.311,421-430(2001))突变侧链，并且使用LSQMAN(Kleywegt,et al.,in International Tables for Crystallography,Vol.F,353-367(KluwerAcademic Publishers,Dordrecht,The Netherlands,2001))实施结构重叠。使用Rosetta程序DDG_MONOMER(Kellogg,et al.,Proteins 79,830-838(2011))计算地评估特定突变的力能学(energetics)。使用Chimera(Pettersen,E.F.,et al.Journal of ComputationalChemistry 25,1605-1612(2004))进行表面积计算。检查蛋白质数据库(PDB)中约700个三聚体结构，以找到合适的三聚化结构域，以进一步稳定化HA-SS免疫原。该搜索揭示了HIV-1gp41(PDB ID 1SZT)针对以下待被优化(i)其大小(每个单体小于70个氨基酸)，(ii)其热稳定性(Tm＝70℃)，(iii)容易移植，其中N-和C-末端位于三聚体的相同末端，和(iv)gp41的内部七价重复1(inner heptad repeat 1,HR1)螺旋的C-端末端与HA-SS三聚体的内部C螺旋之间的结构互补性。Gen1HA-SS不能表达为三聚体，尽管存在C末端折叠物三聚化结构域。
为了增加第二代中的三聚体稳定性，本发明人将HA-SS的膜远端区域处的HA2残基66-85替换为热稳定性HIV-1gp41三聚化结构域(参见Tan,et al.,Proc.Natl.Acad.Sci.U.S.A.94,12303-12308(1997))，其中内部七价重复1(HR1)螺旋在结构上与HA茎的内部C螺旋互补。连接gp41和HA-SS必需循环排列gp41螺旋HR1和HR2，其顺序是颠倒的并用富含甘氨酸的接头重新连接(图1)。为了将HIV-1gp41的融合后形式的六螺旋束插入Gen2HA-SS中，将来自gp41的三个内部螺旋的残基28-32(残基573-577，HXBc2编号)叠加到HA内螺旋残基HA2 81-85(来自PDB ID 1RU7)上，对于15个Cα原子具有的均方根偏差(RMSD)。HA2残基66-85被gp41七价重复(HR)2螺旋(残基628-654，HXBc2编号)替换，随后是含有N-连接的糖基化位点的序列子的六残基富含甘氨酸的接头(NGTGGG)和gp41HR1螺旋(残基548-577)。HR1设计成与HA2的螺旋C符合读码框，以产生长的中心嵌合螺旋。通过加入盐桥，缩短环和降低其疏水性来稳定F’区的膜远端部分的努力没有改善Gen2HA-SS设计的三聚化或抗原性。Gen2HA-SS的表达导致29％的三聚化。
为了改善第三代中的三聚化，除去了具有不规则二级结构的HA1F’区的44个残基的部分，并且HA-SS的内部螺旋C被截短了6个残基，以在gp41和HA2之间具有更好的互补性。这导致具有77％三聚化的可溶性Gen3HA-SS，其被具有与可溶性HA三聚体(图1)的亲和力总体类似的亲和力的HA茎广泛中和性mAb(bNAb)识别。在Gen3中，用GWG接头替换F’区的HA-SSHA2残基43-50和278-313，并除去HA2残基60-65和86-92。为了使gp41与HA茎的下部区域重比对，将来自gp41的三个内部螺旋的残基30-34(575-579Hxbc2编号)叠加到HA内部螺旋残基HA2 90-94上，对于15Cα原子具有的RMSD。对于CR6261和70-5B03观察到更快的解离速率，这可能部分是由于可以与CR6261重链有限接触的HAF’区域的丧失。
为了在原子水平表征Gen3HA-SS，本发明人以分辨率测定了与鼠bNAb C179的抗原结合片段(Fab)复合的Gen3HA-SS的晶体结构(参见Okuno,Y.,et al.J.Virol.67,2552-2558(1993))(图2a，左图)；C179抗体是用异亚型中和发现的第一种广泛中和性HA茎定向抗体。
将从杂交瘤细胞收获的C179切割成Fab，如先前所述(Ofek,G.,etal.J.Virol.78,10724-10737(2004))，其中具有以下修改：LysC(Roche)与C179以1:20,000(w/w)比率使用，并且经由通过在50mM Tris pH 8.0中的巯基-乙基-吡啶柱(Pall LifeSciences)从消化溶液中除去可结晶片段(Fc)，并且用50mM NaAc pH 5.0洗脱C179Fab。
通过使1:1.25(Gen3HA-SS/C179摩尔比)混合物通过Superdex 200 26/60(GEHealthcare)凝胶过滤柱，并且收集在152.0mL洗脱的峰获得Gen3HA-SS(在293GnTI-/-细胞中表达)与C179Fab的复合物。将复合物在150mM NaCl，10mM Tris HCl pH7.5中浓缩至10mg/ml，并且通过在15％(W/V)聚乙二醇1500，5％(V/V)2-甲基-2,4-戊二醇，200mM NH4Cl和100mM Tris HCl pH8.5中的悬滴蒸汽扩散(hanging drop vapor diffusion)在20℃结晶，这来源于沉淀剂协同结晶筛选(Majeed,S.,et al.Structure 11,1061-1070(2003))。在没有任何另外的冷冻保护剂的情况下将晶体冷冻，并在数据收集之前贮存在液氮中。
在Advanced Photon Source(APS),阿贡国家实验室(Argonne NationalLaboratory)的东南地区协作访问团队(Southeast Regional Collaborative AccessTeam,SER-CAT)22-BM束线处，使用的波长，在100K的温度下收集X射线数据到分辨率用HKL2000在三角空间群H3中处理X射线数据，并且通过使用五个单独的搜索模型的分子替换来确定复合物的结构。使用PHASER(Mccoy,A.J.,etal.J.Appl.Crystallogr.40,658-674(2007))，与来自1934PR8结构的HA茎单体(PDB ID1RU7，残基5-36，315-323HA1链A和残基514-559，590-660HA2链B)，HIV-1gp41单体(PDB ID1SZT，残基3-29，42-67)，鼠抗体S25-2的重链可变域(PDB ID 1Q9K，残基1-111)，和鼠抗体MN16C13F4的轻链可变域(PDB ID 1UWX,残基3-108)一起搜索。使用MOLREP(CollaborativeComputational Project.Acta Crystallogr.D Biol.Crystallogr.50,760-763(1994))来定位T4折叠物单体(PDB ID1RFO，链A)，其证实了手工进行的独立拟合。通过眼将C179Fab恒定结构域拟合入Fo-Fc密度中，之后使用上述Ab(PDB ID 1Q9K和1UWX)的恒定结构域作为模板精修。使用COOT(Emsley,P.&Cowtan,K.Coot:D Biol.Crystallogr.60,2126-2132(2004))和PHENIX(Adams,P.D.,et al.Acta Crystallogr.D Biol.Crystallogr.58,1948-1954(2002))及搭乘氢(riding hydrogen)实施模型建立和精修。除了HA切割环(残基48-52)，连接gp41螺旋的富含甘氨酸的环(残基139-144)，连接HA-SS到折叠物的接头(残基256-259)和折叠物域C端的凝血酶切割位点和His标签(残基286-302)外，将Gen3HA-SS的所有残基建模成电子密度。观察到糖并建立在Asn残基23、119和236上。C179结构包括重链残基1-213和轻链残基1-214。如由PHENIX测定的Ramachandran统计学揭示了有利区域中91.64％的残基，允许区域中的7.49％和作为异常值的0.86％。
共晶体结构揭示Gen3HA-SS的C179识别类似于在最近公布的C179与A/日本/305/1957(1957JP)HA的共晶结构中识别H2N2三聚体HA的识别(参见Dreyfus,et al.,J.Virol.87,7149-7154(2013))(图2a，右图)。虽然这些发现证实了Gen3HA-SS上的茎表位的保留；整体结构揭示了几个意想不到的差异(图2a，左图和中图)。首先，茎三聚体亚基在其C末端相对于HA分开约(图2a，中间图)。第二，C-末端折叠物三聚化结构域倒转并且在茎三聚体内部叠入到张开区域中(图2a，左图)。最后，HA茎的外部螺旋A与gp41六螺旋束的外部HR2螺旋形成连续螺旋，而不是形成由甘氨酸接头分开的两个单独的螺旋。
为了解决这些问题，创建了含有三个突变(图1中概述)的第四代HA-SS，以努力除去潜在的侧链碰撞并且破坏HA2的螺旋B与gp41HR2之间的连续螺旋(图2b)。
为了结晶Gen4HA-SS/CR6261复合物，通过与内切糖苷酶H(77U/μg Gen4HA-SS)温育4小时来使Gen4HA-SS(在293GnTI-/-细胞中表达)去糖基化，随后通过刀豆蛋白A柱(Sigma)除去具有未切割的N-连接聚糖的蛋白质。通过使1:1.25(Gen4HA-SS/CR6261摩尔比)混合物通过Superdex 200 10/300(GE Healthcare)凝胶过滤柱并收集在12.5mL处洗脱的峰来获得与CR6261Fab的复合物。将复合物在150mM NaCl，10mM Tris HCl pH7.5中浓缩至11mg/ml，并通过在7％(w/v)聚乙二醇4000，4.5％(v/v)异丙醇，100mM咪唑pH6.5中的悬滴蒸汽扩散在20℃结晶。将晶体在包含另外的5％(v/v)2R,3R丁二醇(Sigma)的贮存溶液中在室温下浸泡6小时，然后简短30秒转移至含有15％2R,3R丁二醇的贮存溶液，之后快速冷却。
在APS的SER-CAT BM-22束线处使用的波长在100K的温度下收集X射线数据到分辨率。用空间群H3中的HKL2000(参考文献37)处理数据，并通过使用三个单独的搜索模型的分子置换来确定复合物的结构。使用PHASER来与来自1934PR8结构的HA茎单体，HIV-1gp41单体(与上述相同模型)以及CR6261(PDB ID 3GBM)的可变和恒定结构域一起搜索。分别使用COOT和PHENIX进行模型建立和精制。除了HA切割环(残基48-52)，连接gp41螺旋的富含甘氨酸的环(残基137-145)和C末端折叠物(残基256-259)，折叠结构域C端的凝血酶切割位点和His标签(残基286-302)外，将Gen4HA-SS的所有残基建模为电子密度。尽管在Gen3HA-SS结构中观察到的相同区域中的HA茎内部可见密度，但是它不足以唯一放置或稳定精制折叠物结构域。CR6261Fab结构包括重链残基1-213和轻链残基3-107和113-215。如由PHENIX测定的Ramachandran统计学揭示有利区域中93.19％的残基，允许区域中的6.09％和作为异常值的1.06％。
对于低温电子显微术分析，使用Vitrobot Mark IV(FEI Company,Hillsboro,OR)在多孔碳膜(Quantfoil,Germany)上将颗粒玻璃化。在Titan Krios电子显微镜(FEI公司，Hillsboro，OR)上收集颗粒的冷冻图像，在液氮温度下操作并在300kV下操作。在像素大小以范围为约2.8至约6μm的散焦值，并且以范围为约10至的剂量在4,096×4,096电荷耦合器件(CCD)照相机(Gatan Inc.，Warrendale，PA)上收集图像。使用ctffind3(Mindell,J.A.&Grigorieff,N.J Struct Biol 142,334-347(2003))拟合观察到的散焦值，并且将展示漂移或散光的图像从进一步分析中排除。从图像中手动挑选颗粒(13,464)。无参考2D分类指示在3D精修期间施加的八面体对称。使用平滑，无刺突的低通滤过的铁蛋白(PDB ID 2JD6)作为起始模型。在精化过程中除去重叠颗粒之后，从6,540个颗粒计算重建(3D图)。用Relion包(Scheres,S.H.W.J.Mol.Biol.415,406-418(2012))进行所有图像分析(2D和3D)。用Chimera进行模型坐标的可视化和分子停靠。
与C179复合的Gen3HA-SS和与CR6261复合的Gen4HA-SS复合物的原子坐标和结构因子分别保存在PDB代码4MKD和4MKE下。H1-SS-np的冷冻电子显微术图已经以EMDB代码EMD-6332保存。
与bNAb CR6261的Fab复合的Gen4HA-SS的分辨率的共晶体结构(参见Ekiert,D.C.,et al.Science 324,246-251(2009))揭示了相对于gp41的展开仍然存在，额外旋转约19°(图2b，中间图)。然而，在Gen4HA-SS中三聚化水平(83％)，茎表位构象的保持和HA茎bNAb结合(对四种bNAb为nM)接近最佳(图1a和2b)。
发明人关注免疫原性HIV-1gp41区域的牵连，因此寻求用短的富含甘氨酸的接头替换gp41(图1a)，因为这还将增加HA茎在免疫原表面上的百分比(图1b)。在两种情况，Gen5HA-SS(其保留Gen4稳定化茎区)和Gen6HA-SS(其中包含Lys51-Glu103(HA2，H3编号)的内部盐桥被替换为几乎等排的Met-Leu疏水对)(Gen6HA-SS，图1c)下进行gp41替换。
通过完全除去gp41三聚化结构域，将HA2残基58-93与GSGGSG环连接并引入HA2突变Y94D和N95L来创建Gen5HA-SS。
为了设计Gen6HA-SS，最初创建了五个突变以稳定化HA茎HA2的内部核心：K51M，E103L，E105Q，R106W和D109L(称为Gen6’HA-SS)。对所有三种免疫原保留通过HA茎抗体的三聚化和识别(图1a)。包含三个另外的内部稳定化突变的Gen6HA-SS的中间形式(称为Gen6’HA-SS)展示相似的抗原性(图1d)，但是最终观察到突变E105Q，R106W和D109L不是稳定化Gen6HA-SS和与铁蛋白融合需要的，并且不用于最终的H1-SS-np构建体(图1c)。
实施例2：自组装铁蛋白纳米颗粒的创建
该实施例描述了Gen4，Gen5，Gen6’和Gen6HA-SS通过它们各自的HA C末端与自组装铁蛋白纳米颗粒的融合。
在自组装纳米颗粒(HA-np)的背景下，HA的免疫原性显著增加(参见Kanekiyo,M.,et al.,Nature 499,102-106(2013))。此外，本发明人推测与纳米颗粒的C-末端融合可以降低茎的近膜区域的张开。因此，本发明人将Gen4，Gen5，Gen6’和Gen6HA-SS通过它们各自的HA C-末端(替换折叠物)遗传融合到幽门螺杆菌的自组装铁蛋白纳米颗粒以创建HA-SS-纳米颗粒(HA-SS-np)。
用SGG接头将Gen4-6HA-SS与幽门螺杆菌铁蛋白N-末端(残基5-167)融合以产生HA-SS铁蛋白纳米颗粒(Gen4HA-SS-np,H1-SS-np和H1-SS-np’)，如描述的(Kanekiyo,M.,etal.Nature 499,102-106(2013))。
使用fortéBio Octet Red384仪器测量HA和HA-SS分子对mAb CR6261，CR9114，F10scFv和70-5B03的结合动力学。所有测定法在30℃下进行，在补充有1％BSA的PBS中设定为1,000rpm的搅拌，以使非特异性相互作用最小化。所有溶液的最终体积为100μl/孔。在固体黑色96孔板(Geiger Bio-One)中在30℃进行测定。使用在10mM乙酸盐pH 5.0缓冲液中具有C-末端生物素化的Avi-Tag(25μg/ml)和HA-np或HA-SS-np的HA或HA-SS分别加载链霉抗生物素蛋白和胺反应性生物传感器探针达300s。典型的捕获水平在0.8和1nm之间，并且一排八个尖端内的变异性不超过0.1nm。将生物传感器尖端在PBS/1％BSA缓冲液中平衡300s，之后进行溶液中的Fab或F10scFv(0.01至0.5μM)的结合测量。加入抗体后，使结合进行300s；然后使结合解离300s。仅使用解离孔一次以防止污染。通过减去对于在PBS/1％BSA中温育的装载有HA或HA-SS分子的传感器记录的测量，进行平行校正以减去系统基线漂移。为了除去非特异性结合应答，将生物素化的gp120表面重修核心分子加载到链霉抗生物素蛋白探针上，并与抗茎抗体一起温育，并从HA和HA-SS响应数据中减去非特异性应答。使用Octet软件7.0版进行数据分析和曲线拟合。实验数据用描述1:1相互作用的结合方程拟合。假设结合是可逆的(完全解离)，使用非线性最小二乘法拟合进行完整数据集的全局分析，所述非线性最小二乘法拟合允许对于每个实验中使用的所有浓度同时获得单一组的结合参数。
如之前所述(Wei,C.J.,et al.Science 329:1060-1064(2010))进行ELISA，血凝抑制(HAI)测定法和假型中和测定法。如描述(Wei,C.J.,et al.Sci.Transl.Med.2,24ra21(2010))，产生表达萤光素酶报告基因的重组HA/NA慢病毒载体。所有流感病毒均获自疾病控制和预防中心(CDC；Atlanta，GA)。
Gen4，Gen6和Gen6’HA-SS-np各自表示为纳米颗粒，如通过透射电子显微镜分析和凝胶过滤证实的(图2)。然而，Gen5HA-SS-np未能表达。选择Gen6和Gen6’HA-SS-np进行进一步评估，并且在下文中在这些实施例中分别称为H1-SS-np和H1-SS-np’。以分辨率为实施的H1-SS-np的冷冻电子显微术(EM)分析揭示了对称的球形颗粒，每个颗粒具有从表面突出的八个刺突(图2c)。值得注意的是，Gen6HA-SS茎的膜近端区域比Gen4HA-SS更好地适合于电子密度，这表明扩展是减轻的或不再存在(图2c，左图)。此外，H1-SS-np和H1-SS-np’都具有期望的抗原性，在ELISA和生物层干涉测量法测量中被CR6261，CR9114，F10和70-5B03识别(参见Ekiert,D.C.,et al.Science 324,246-251(2009)；Sui,J.,etal.Nat.Struct.Mol.Biol.16,265-273(2009)；Dreyfus,C.,et al.Science 337,1343-1348(2012)；Wrammert,J.,et al.J.Exp.Med.208,181-193(2011))，表明在与铁蛋白融合后保留了真正的HA-SS结构(图1a，1e和1f)。
实施例3：评估疫苗功效
该实施例证明了与HA构建体融合的铁蛋白纳米颗粒的疫苗功效的各种测量的表征。
本发明人使用钙流量测定法评估了与全长HA-np相比H1-SS-np通过膜锚定的种系恢复的CR6261B细胞受体(BCR)触发信号传导的能力(Novak,et.al.Cytometry 17,135-141(1994))。
对于BCR活化测定法，通过轻链和膜锚定的IgM重链对Ramos B细胞系的表面IgM阴性克隆的慢病毒转染(FEEKW载体；Luo,X.M.,et al.Blood 113,1422-1431(2009))稳定表达种系CR6261BCR(野生型和双重I53A/F54A突变体)。然后通过流式细胞术(BD FACSAria；BD Biosciences)分选种系CR6261BCR阳性细胞并扩增。评估对于种系CR6261BCR(野生型或I53A/F54A突变体)表达>95％阳性的细胞的表面表达和正确的HA抗原性。对于信号传导，向表达种系CR6261BCR的1×106个Ramos B细胞呈现2500nM的H1-SS-np，HA np(HA含有Y98F突变以消除与唾液酸的非特异性结合)或空np。通过流式细胞术测量响应于BCR刺激的钙流量的动力学，作为染料Fura Red的Ca2+结合/未结合状态的比率。Ca2+流量的此比率在暴露于配体后10秒呈现。在刺激之前获取30秒基线。对单个细胞的参比测量取平均值并通过动力学分析，FlowJo软件变平滑。在暴露于0.5μg/μl抗人IgM F(ab’)2(Southern Biotech)后，通过Ca2+流量比较种系CR6261BCR对具有I53A/F54A突变的种系CR6261BCR之间的功能性。
与空铁蛋白颗粒相反，H1-SS-np通过野生型BCR诱导有效的信号传导，全长HA-np在较小程度上亦然，并且通过在第二个重链互补决定区(CDR H2)中的两个关键接触残基中突变的BCR没有观察到信号传导(图1g)。这一发现证实了H1-SS-np衔接CR6261的IGHV1-69种系前体并通过CDR H2依赖性识别刺激未免疫的B细胞的能力，在人中发现的广泛中和性茎定向抗体的特征。
为了评估H1-SS-np疫苗功效，本发明人使用Sigma佐剂系统(SAS)免疫小鼠和雪貂，这是因为已报道类似于MF59(另一种被批准用于人的基于角鲨烯的佐剂)，SAS诱导HA响应。
对于免疫研究，对于该研究进行总共三个动物实验，两个在小鼠中，一个在雪貂中。在第一次小鼠实验中，在第0周和第2周时用2μg H1-SS-np，2μg空白铁蛋白np，0.2μg H52005IND HA-np或TIV(HA摩尔当量)肌肉内免疫雌性BALB/c小鼠(6-8周龄，JacksonLaboratories)。在每次免疫后14天收集血液，并且分离血清。对于第二次小鼠免疫实验，在第0周、第8周和第12周用3μg的H1-SS-np或空铁蛋白np免疫雌性BALB/c小鼠三次。对于雪貂免疫，饲养使用6月龄雄性Fitch雪貂(Triple F Farms,Sayre,PA)(对于暴露于目前循环的大流行H1N1，季节性H1N1，H3N2和B流感毒株呈血清阴性)，并在BIOQUAL，Inc.(Rockville，MD)护理。这些设施由美国实验动物保护国际认可协会(American Association for theAccreditation of Laboratory Animal Care International)认可，并满足NIH标准，如“实验动物护理和使用指南(Guide for the Care and Use of Laboratory Animals)”中所述。在第0周和第4周，用在500μl PBS中的20μg H1-SS-np’或空铁蛋白np或TIV(相当于2.5μg H1HA)肌内免疫雪貂。用250μg表达H5 2005IND的质粒DNA，随后在第0周和第4周用H5N1 2005IND MIV的2.5μg HA免疫阳性对照组中的雪貂。通过肌内注射将疫苗施用到大腿上部肌肉中。Sigma佐剂系统(SAS，Sigma)用于所有蛋白质或基于np的免疫。每次免疫后14天收集血液，并且分离血清。动物实验完全符合所有相关联邦规定和NIH指南进行。
对于被动转移研究，在第0周和第4周首先用H1-SS-np蛋白(2μg/剂量，具有SAS)接种150只小鼠，以产生HA-SS免疫Ig，并在加强后第1周，第2周和第3周(末端)收集血清。使用制造商方案用蛋白G(Life Technologies)纯化来自免疫血清的Ig。攻击前24小时，两组BALB/c小鼠(n＝10/组，Taconic inc。)通过腹膜内途径接受未免疫的(Molecularinnovations)或免疫的Ig。在被动转移后24小时从输注的动物收集血清用于血清学分析。
对于病毒攻击研究，从疾病控制和预防中心(Atlanta,GA)(CDC#2004706280,E1/E3(1/19/07)获得H5N1毒株A/越南/1203/04，并且在BIOQUAL Inc.在10天龄的胚胎鸡蛋(Charles River,North Franklin,CT)中扩充。攻击原液具有1010TCID50/ml的感染滴度。对于血液收集，放血和攻击程序，用配制为对每只动物提供25mg/kg氯胺酮和0.001mg/kg右美托咪定剂量的氯胺酮/右美托咪定溶液麻醉动物。将小鼠用50μl病毒鼻内接种，每个鼻孔大约25μl，并且对雪貂鼻内接种500μl病毒，每个鼻孔约250μl。攻击剂量为小鼠中的25LD50和雪貂中的1000TCID50。根据以前的研究，这些攻击剂量预期分别导致未免疫的对照小鼠和雪貂中的100％致死率。对于雪貂，每天记录感染的临床体征，体重和温度两次。如下分配活动得分：0，警惕和嬉戏；1，警醒但只在受刺激时嬉戏(playful)；2，警惕，但刺激时不嬉戏；和3，既不警惕，在刺激时也不嬉戏。对显示严重疾病体征(延长的发烧，腹泻，干扰饮食，饮水或呼吸的流涕；严重嗜睡；或神经学体征)或体重减轻>20％的雪貂立即实施安乐死。
H1-SS-np和H1-SS-np’分别引发在小鼠和雪貂两者中针对组1HA亚型(季节性和大流行H1，H2，H5和H9)的广泛抗体响应(图3a，3b和3C)。此外，H1-SS-np在半数的小鼠中诱导出与H2和H5相当的实质性组2(H3和H7)应答(图3a，左图)。在小鼠和雪貂两者中，由H1-SS-np引发的对HA茎的抗体应答显著高于三价灭活的流感疫苗(TIV)的抗体应答(图3b，右图)。虽然也观察到对铁蛋白的相当大的应答(图3a和3b，左图)，但先前的研究已显示用细菌铁蛋白免疫不诱导小鼠中自体铁蛋白的免疫，它也不减轻对随后免疫的HA特异性抗体应答。使用高度灵敏的HA-NA慢病毒报告物测定法(Wei,C.J.,et al.Sci.Transl.Med.2,24ra21(2010))测量血清中和活性(NT)揭示了在小鼠和雪貂两者中针对趋异的H1N1毒株A/加利福尼亚/04/2009(2009CA)和A/新加坡/6/1986(1986SG)和同源1999NC株的看得出的活性。然而，针对异亚型H5N1A/越南/1203/2004(H5N1 2004VN)，人起源H2N2A/加拿大/720/2005(H2N2 2005CA)，H7N9A/安徽(Anhui)/1/2013(H7N9 2013AN)和H9N2A/香港/1074/1999(H9N2 1999HK)在小鼠和雪貂两者中都是低的或不可检测的(图3a和3c)。尽管强的异亚型抗体反应性，但观察到的最小异亚型中和可能是由于茎中和所需要的单个表位区域的精确靶向，使得其比在表面积上大20倍的HA茎的其它部分对次要结构差异更敏感。TIV免疫的动物在小鼠和雪貂两者中具有针对同源1999NC的最高NT，针对异源H1N1株的可检测NT，以及没有针对异亚型H5N1的NT(图3b)。如预期的，TIV免疫的动物具有显著的血凝抑制(HAI)滴度，并且由H1-SS-np和H1-SS-np’引发的NT活性与HAI无关。
为了评估保护，用高致死剂量的高致病性H5N1 2004VN病毒攻击经免疫的小鼠和雪貂。所有未免疫的小鼠和用空np免疫的小鼠死亡，并且显著地，所有用H1-SS-np免疫的小鼠存活(图4a)。用空铁蛋白纳米粒免疫的所有雪貂死于感染，并且用H5N1HA DNA/单价灭活疫苗(MIV)初免-加强免疫的所有雪貂存活(图4b)。与小鼠研究一致，六个基于H1N1的H1-SS-np’免疫的雪貂中的四个幸免于H5N1攻击。尽管六个TIV免疫的雪貂中的两个存活，但是两个存活者中的一个经历严重的体重减轻(图4a)，并且在具有最小体重减轻的另一只存活者中没有H5血清学应答的证据，提示没有发生感染。除了一个血清阴性动物之外，与空的铁蛋白-np对照相比，TIV免疫的组在体重减轻或发烧方面没有差异，并且如通过攻击后活动评分证明，比H1-SS-np’-免疫的雪貂显示更大的疾病。与空铁蛋白免疫的对照相比，基于H1-SS-np’-免疫的雪貂中的活动评分，第6天体重减轻，发热和疾病显著减少(图4)。在存活的雪貂中攻击后第14天存在的针对H5N1 2004VN的HAI滴度指示虽然H1-SS-np’能够预防疾病，但它不能防止感染。表3和4提供了小鼠和雪貂中的这些免疫研究的总结。
表3：在用H1-SS-np免疫的小鼠中针对H1N1 1999NC和H5N1 2004VN的攻击后血清HAI抗体滴度。
*此小鼠在攻击前1天死亡。
表4：用指定方案免疫的雪貂中针对同源H1N1 1999NC的攻击前HAI抗体滴度和针对攻击毒株H5N1 2004VN的攻击后HAI抗体滴度。
由H1-SS-np’引发的可忽略的H5N1NT活性(图3c)没有解释观察到的异亚型保护。然而，在HA-SS-np’免疫的白鼬中，HA抗体滴度和存活之间以及抗体滴度和体重之间存在相关性。为了进一步研究这种相关性，在用高致死剂量的H5N1 2004VN病毒攻击前24小时，发明人被动转移H1-SS-np免疫Ig至未免疫的小鼠(10mg/动物)。转移的Ig具有与组1HA亚型(H1，H2，H5和H9)的强反应性，与组2亚型(H3和H7)的较弱的结合和最小的NT活性(图4d和4e)。在表5中显示H1-SS-np免疫Ig对多种流感假病毒的IC50中和滴度。
表5：H1-SS-np免疫Ig的IC50假病毒中和滴度。
虽然所有接受未免疫的Ig的小鼠都死于感染，但接受免疫Ig的10只小鼠中的8只完全被保护而免于致命的H5N1异亚型攻击。在免疫Ig组中死亡的两只小鼠中对同源H11999NC HA的低血清反应性指示它们可能尚未接受适当的Ig施用(图4c)。
这些数据一起显示，基于除中和之外的功能机制(如抗体依赖性细胞介导的细胞毒性(ADCC)或抗体依赖性补体介导的裂解)的抗体介导的的保护负责由H1-SS-np和H1-SS-np’免疫引发的保护。报告了通过广泛中和性HA茎抗体在小鼠中的流感保护依赖于Fc相互作用(DiLillo,et.al.Nat Med 20,143-151(2014))，并且已经在人和猕猴血浆两者中报告了在不存在中和的情况下针对流感HA的交叉反应性ADCC(Jegaskanda,S.,et al.JImmunol 190,1837-1848(2013)；Jegaskanda,et al.J.Virol.87,5512-5522(2013)；Jegaskanda,et al.J Immunol 193,469-475(2014))。与这些报告一致，本文中呈现的结果提示基于HA茎的流感疫苗不需要必然聚焦于中和性表位以诱导广泛的保护。
使用基于结构的设计并避免对HA头部结构域的免疫显性应答，与纳米颗粒抗原展示平台组合，本发明人成功地产生了仅HA茎的纳米颗粒疫苗免疫原，其在雪貂中引发针对H5N1疾病的抗体介导的异亚型保护性免疫。这些结果证明，通过仅HA茎的纳米颗粒疫苗引发非中和性抗体可以提供针对严重疾病的广泛保护，并且应该用于开发通用流感疫苗。
序列表
<110> 美利坚合众国, 由健康及人类服务部部长代表
Mascola, John R.
Boyington, Jeffrey C.
Yassine, Hadi M.
Kwong, Peter D.
Graham, Barney S.
Kanekiyo, Masaru
<120> 稳定化的流感血凝素茎区三聚体及其用途
<130> 6137NIAID-36-PCT
<140> 尚未分配
<141> 2015-05-27
<150> 62/003,471
<151> 2014-05-27
<160> 401
<170> PatentIn version 3.5
<210> 1
<211> 504
<212> DNA
<213> 幽门螺杆菌
<400> 1
atgctgtccg acatcatcaa gctgctgaac gaacaggtga acaaggagat gcagagctcc 60
aacctgtaca tgagtatgtc tagttggtgt tatacacact cactggacgg cgctgggctg 120
ttcctgtttg atcacgcagc cgaggaatac gaacatgcaa agaaactgat cattttcctg 180
aatgagaaca atgtgcccgt ccagctgact tcaatcagcg cccctgaaca taagttcgag 240
ggcctgaccc agatctttca gaaagcttac gaacacgagc agcatatttc cgaatctatc 300
aacaatattg tggaccacgc cattaagagc aaagatcatg ctaccttcaa ctttctgcag 360
tggtacgtgg ccgagcagca cgaggaggag gtcctgttta aggacatcct ggataaaatc 420
gaactgattg gaaacgagaa tcatggcctg tacctggcag atcagtatgt gaagggcatt 480
gccaagtcca gaaaaagtgg gtca 504
<210> 2
<211> 168
<212> PRT
<213> 幽门螺杆菌
<400> 2
Met Leu Ser Asp Ile Ile Lys Leu Leu Asn Glu Gln Val Asn Lys Glu
1 5 10 15
Met Gln Ser Ser Asn Leu Tyr Met Ser Met Ser Ser Trp Cys Tyr Thr
20 25 30
His Ser Leu Asp Gly Ala Gly Leu Phe Leu Phe Asp His Ala Ala Glu
35 40 45
Glu Tyr Glu His Ala Lys Lys Leu Ile Ile Phe Leu Asn Glu Asn Asn
50 55 60
Val Pro Val Gln Leu Thr Ser Ile Ser Ala Pro Glu His Lys Phe Glu
65 70 75 80
Gly Leu Thr Gln Ile Phe Gln Lys Ala Tyr Glu His Glu Gln His Ile
85 90 95
Ser Glu Ser Ile Asn Asn Ile Val Asp His Ala Ile Lys Ser Lys Asp
100 105 110
His Ala Thr Phe Asn Phe Leu Gln Trp Tyr Val Ala Glu Gln His Glu
115 120 125
Glu Glu Val Leu Phe Lys Asp Ile Leu Asp Lys Ile Glu Leu Ile Gly
130 135 140
Asn Glu Asn His Gly Leu Tyr Leu Ala Asp Gln Tyr Val Lys Gly Ile
145 150 155 160
Ala Lys Ser Arg Lys Ser Gly Ser
165
<210> 3
<211> 504
<212> DNA
<213> 幽门螺杆菌
<400> 3
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcggaca gcat 504
<210> 4
<211> 492
<212> DNA
<213> A流感病毒
<400> 4
atcatcaagc tgctgaacga acaggtgaac aaggagatgc agagctccaa cctgtacatg 60
agtatgtcta gttggtgtta tacacactca ctggacggcg ctgggctgtt cctgtttgat 120
cacgcagccg aggaatacga acatgcaaag aaactgatca ttttcctgaa tgagaacaat 180
gtgcccgtcc agctgacttc aatcagcgcc cctgaacata agttcgaggg cctgacccag 240
atctttcaga aagcttacga acacgagcag catatttccg aatctatcaa caatattgtg 300
gaccacgcca ttaagagcaa agatcatgct accttcaact ttctgcagtg gtacgtggcc 360
gagcagcacg aggaggaggt cctgtttaag gacatcctgg ataaaatcga actgattgga 420
aacgagaatc atggcctgta cctggcagat cagtatgtga agggcattgc caagtccaga 480
aaaagtgggt ca 492
<210> 5
<211> 165
<212> PRT
<213> A流感病毒
<400> 5
Asp Ile Ile Lys Leu Leu Asn Glu Gln Val Asn Lys Glu Met Gln Ser
1 5 10 15
Ser Asn Leu Tyr Met Ser Met Ser Ser Trp Cys Tyr Thr His Ser Leu
20 25 30
Asp Gly Ala Gly Leu Phe Leu Phe Asp His Ala Ala Glu Glu Tyr Glu
35 40 45
His Ala Lys Lys Leu Ile Ile Phe Leu Asn Glu Asn Asn Val Pro Val
50 55 60
Gln Leu Thr Ser Ile Ser Ala Pro Glu His Lys Phe Glu Gly Leu Thr
65 70 75 80
Gln Ile Phe Gln Lys Ala Tyr Glu His Glu Gln His Ile Ser Glu Ser
85 90 95
Ile Asn Asn Ile Val Asp His Ala Ile Lys Ser Lys Asp His Ala Thr
100 105 110
Phe Asn Phe Leu Gln Trp Tyr Val Ala Glu Gln His Glu Glu Glu Val
115 120 125
Leu Phe Lys Asp Ile Leu Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn
130 135 140
His Gly Leu Tyr Leu Ala Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser
145 150 155 160
Arg Lys Ser Gly Ser
165
<210> 6
<211> 492
<212> DNA
<213> A流感病毒
<400> 6
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg at 492
<210> 7
<211> 1695
<212> DNA
<213> A流感病毒
<400> 7
atgaaggcca aactgctggt gctgctgtgt acctttaccg ccacctacgc cgacacaatc 60
tgtatcggct accacgccaa caatagcacc gacaccgtgg atacagtgct ggagaagaac 120
gtgaccgtga cccactctgt gaacctgctg gaggacagcc acaatggcaa gctgtgtctg 180
ctgaaaggca ttgcccctct gcagctgggc aattgttctg tggccggatg gattctgggc 240
aaccccgagt gtgagctgct gatttctaag gagagctgga gctacatcgt ggagaccccc 300
aatcctgaga atggcacctg ctaccctggc tacttcgccg attacgagga gctgcgcgag 360
cagctgtcta gcgtgtccag cttcgagaga ttcgagatct tccccaagga gtccagctgg 420
cctaatcaca cagtgacagg cgtgtctgcc agctgtagcc acaacggcaa aagcagcttc 480
taccggaacc tgctgtggct gacaggcaag aatggcctgt accccaacct gagcaagagc 540
tacgtgaaca acaaggaaaa ggaagtgctg gtgctgtggg gagtgcacca ccctcccaac 600
atcggaaatc agcgggccct gtaccacaca gagaacgcct atgtgagcgt ggtgtccagc 660
cactacagca gaagattcac ccccgagatc gccaagagac ccaaagtgag agaccaggag 720
ggccggatca attactactg gaccctgctg gagcctggcg ataccatcat cttcgaggcc 780
aacggcaatc tgatcgcccc ttggtatgcc tttgccctga gcagaggctt tggcagcggc 840
atcatcacaa gcaacgcccc catggatgag tgtgatgcca agtgccagac acctcagggc 900
gccatcaata gcagcctgcc cttccagaat gtgcaccctg tgaccatcgg cgagtgcccc 960
aagtatgtga gaagcgccaa gctgagaatg gtgaccggcc tgagaaacat ccctagcatc 1020
cagagcagag gactgtttgg agccatcgcc ggattcatcg agggaggatg gacaggcatg 1080
gtggatggct ggtacggcta ccaccaccag aatgagcagg gctctggata tgccgccgat 1140
cagaagtcta cccagaacgc catcaacggc atcaccaaca aggtgaacag cgtgatcgag 1200
aagatgaaca cccagtttac cgctgtgggc aaggagttca acaagctgga gcggaggatg 1260
gagaacctga acaagaaggt ggacgacggc tttctggaca tctggaccta caatgccgaa 1320
ctcctggtcc tcctcgagaa tgagaggacc ctggacttcc acgacagcaa cgtgaagaac 1380
ctgtatgaga aggtgaagag ccagctgaag aacaacgcca aggagatcgg caacggctgc 1440
ttcgagttct accacaagtg taacaacgag tgtatggaga gcgtgaagaa cggcacctac 1500
gactacccta agtacagcga ggagagcaag ctgaaccggg agaagatcga tggcgtgaag 1560
ctggagagca tgggcgtgta tcagatcctg gccatctaca gcacagtggc ctcttctctg 1620
gtgctgctgg tgtctctggg cgccatctcc ttttggatgt gctccaacgg cagcctgcag 1680
tgcaggatct gtatc 1695
<210> 8
<211> 565
<212> PRT
<213> A流感病毒
<400> 8
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Leu Glu Asp Ser His Asn Gly Lys Leu Cys Leu Leu Lys Gly Ile
50 55 60
Ala Pro Leu Gln Leu Gly Asn Cys Ser Val Ala Gly Trp Ile Leu Gly
65 70 75 80
Asn Pro Glu Cys Glu Leu Leu Ile Ser Lys Glu Ser Trp Ser Tyr Ile
85 90 95
Val Glu Thr Pro Asn Pro Glu Asn Gly Thr Cys Tyr Pro Gly Tyr Phe
100 105 110
Ala Asp Tyr Glu Glu Leu Arg Glu Gln Leu Ser Ser Val Ser Ser Phe
115 120 125
Glu Arg Phe Glu Ile Phe Pro Lys Glu Ser Ser Trp Pro Asn His Thr
130 135 140
Val Thr Gly Val Ser Ala Ser Cys Ser His Asn Gly Lys Ser Ser Phe
145 150 155 160
Tyr Arg Asn Leu Leu Trp Leu Thr Gly Lys Asn Gly Leu Tyr Pro Asn
165 170 175
Leu Ser Lys Ser Tyr Val Asn Asn Lys Glu Lys Glu Val Leu Val Leu
180 185 190
Trp Gly Val His His Pro Pro Asn Ile Gly Asn Gln Arg Ala Leu Tyr
195 200 205
His Thr Glu Asn Ala Tyr Val Ser Val Val Ser Ser His Tyr Ser Arg
210 215 220
Arg Phe Thr Pro Glu Ile Ala Lys Arg Pro Lys Val Arg Asp Gln Glu
225 230 235 240
Gly Arg Ile Asn Tyr Tyr Trp Thr Leu Leu Glu Pro Gly Asp Thr Ile
245 250 255
Ile Phe Glu Ala Asn Gly Asn Leu Ile Ala Pro Trp Tyr Ala Phe Ala
260 265 270
Leu Ser Arg Gly Phe Gly Ser Gly Ile Ile Thr Ser Asn Ala Pro Met
275 280 285
Asp Glu Cys Asp Ala Lys Cys Gln Thr Pro Gln Gly Ala Ile Asn Ser
290 295 300
Ser Leu Pro Phe Gln Asn Val His Pro Val Thr Ile Gly Glu Cys Pro
305 310 315 320
Lys Tyr Val Arg Ser Ala Lys Leu Arg Met Val Thr Gly Leu Arg Asn
325 330 335
Ile Pro Ser Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe
340 345 350
Ile Glu Gly Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His
355 360 365
His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr
370 375 380
Gln Asn Ala Ile Asn Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu
385 390 395 400
Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn Lys Leu
405 410 415
Glu Arg Arg Met Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe Leu
420 425 430
Asp Ile Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn Glu
435 440 445
Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys
450 455 460
Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly Cys
465 470 475 480
Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser Val Lys
485 490 495
Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu Asn
500 505 510
Arg Glu Lys Ile Asp Gly Val Lys Leu Glu Ser Met Gly Val Tyr Gln
515 520 525
Ile Leu Ala Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu Leu Val
530 535 540
Ser Leu Gly Ala Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln
545 550 555 560
Cys Arg Ile Cys Ile
565
<210> 9
<211> 1695
<212> DNA
<213> A流感病毒
<400> 9
gatacagatc ctgcactgca ggctgccgtt ggagcacatc caaaaggaga tggcgcccag 60
agacaccagc agcaccagag aagaggccac tgtgctgtag atggccagga tctgatacac 120
gcccatgctc tccagcttca cgccatcgat cttctcccgg ttcagcttgc tctcctcgct 180
gtacttaggg tagtcgtagg tgccgttctt cacgctctcc atacactcgt tgttacactt 240
gtggtagaac tcgaagcagc cgttgccgat ctccttggcg ttgttcttca gctggctctt 300
caccttctca tacaggttct tcacgttgct gtcgtggaag tccagggtcc tctcattctc 360
gaggaggacc aggagttcgg cattgtaggt ccagatgtcc agaaagccgt cgtccacctt 420
cttgttcagg ttctccatcc tccgctccag cttgttgaac tccttgccca cagcggtaaa 480
ctgggtgttc atcttctcga tcacgctgtt caccttgttg gtgatgccgt tgatggcgtt 540
ctgggtagac ttctgatcgg cggcatatcc agagccctgc tcattctggt ggtggtagcc 600
gtaccagcca tccaccatgc ctgtccatcc tccctcgatg aatccggcga tggctccaaa 660
cagtcctctg ctctggatgc tagggatgtt tctcaggccg gtcaccattc tcagcttggc 720
gcttctcaca tacttggggc actcgccgat ggtcacaggg tgcacattct ggaagggcag 780
gctgctattg atggcgccct gaggtgtctg gcacttggca tcacactcat ccatgggggc 840
gttgcttgtg atgatgccgc tgccaaagcc tctgctcagg gcaaaggcat accaaggggc 900
gatcagattg ccgttggcct cgaagatgat ggtatcgcca ggctccagca gggtccagta 960
gtaattgatc cggccctcct ggtctctcac tttgggtctc ttggcgatct cgggggtgaa 1020
tcttctgctg tagtggctgg acaccacgct cacataggcg ttctctgtgt ggtacagggc 1080
ccgctgattt ccgatgttgg gagggtggtg cactccccac agcaccagca cttccttttc 1140
cttgttgttc acgtagctct tgctcaggtt ggggtacagg ccattcttgc ctgtcagcca 1200
cagcaggttc cggtagaagc tgcttttgcc gttgtggcta cagctggcag acacgcctgt 1260
cactgtgtga ttaggccagc tggactcctt ggggaagatc tcgaatctct cgaagctgga 1320
cacgctagac agctgctcgc gcagctcctc gtaatcggcg aagtagccag ggtagcaggt 1380
gccattctca ggattggggg tctccacgat gtagctccag ctctccttag aaatcagcag 1440
ctcacactcg gggttgccca gaatccatcc ggccacagaa caattgccca gctgcagagg 1500
ggcaatgcct ttcagcagac acagcttgcc attgtggctg tcctccagca ggttcacaga 1560
gtgggtcacg gtcacgttct tctccagcac tgtatccacg gtgtcggtgc tattgttggc 1620
gtggtagccg atacagattg tgtcggcgta ggtggcggta aaggtacaca gcagcaccag 1680
cagtttggcc ttcat 1695
<210> 10
<211> 1698
<212> DNA
<213> A流感病毒
<400> 10
atgaaggcta ttttggtcgt gctcctgtac acctttgcca cagccaatgc cgataccctt 60
tgtattggct accatgcaaa caactctacc gatacggtcg acacggtgct cgaaaagaat 120
gttactgtca cccactctgt gaacttgctg gaggataaac acaatggcaa gctctgcaaa 180
ctgcgagggg tggctcccct gcatctggga aaatgtaata ttgccggctg gatactgggt 240
aatccagaat gcgaatcctt gagtacggca tccagttggt cctatatcgt cgagaccccg 300
tcaagtgaca atgggacctg ctacccaggc gacttcattg attatgaaga gctgagggag 360
cagttgtcat ccgtaagcag cttcgaaagg tttgagattt tcccgaaaac tagctcctgg 420
cccaatcatg actctaacaa aggagttact gcagcctgtc ctcatgcggg cgcgaaaagc 480
ttctacaaga acctgatatg gctcgtgaag aaaggcaatt catacccaaa actgtctaag 540
agctacataa acgataaagg gaaagaggtt ctggtgcttt ggggcataca ccacccatct 600
acctcagccg accagcagtc tctgtatcag aacgccgaca catacgtgtt tgtgggcagc 660
tcccgctatt ctaagaagtt caaacccgag atcgccatca gaccaaaggt gagagaccag 720
gaaggaagga tgaattatta ctggaccttg gtcgaacctg gcgataagat aacgtttgag 780
gctacgggca acctggtcgt gccgagatat gcttttgcca tggagaggaa tgcggggagc 840
ggaattatca tcagcgacac tccagttcat gactgtaata ccacatgtca gacaccgaag 900
ggcgccatca acacgagctt gccctttcag aatatacatc caatcacaat cggaaaatgc 960
cccaagtacg tgaaaagcac taaactgaga ctcgccaccg gactcaggaa tatcccaagc 1020
atccagtcac ggggtctgtt cggcgctatc gccggattta ttgaaggcgg ctggacgggg 1080
atggtggacg gttggtacgg ctaccatcat caaaatgagc agggctccgg atacgccgct 1140
gacctgaaat ctacgcagaa tgccatagat gagatcacaa acaaggtcaa tagtgtgata 1200
gaaaaaatga atactcagtt cacagctgtt ggaaaggagt ttaaccacct cgagaagcga 1260
attgagaacc tgaacaagaa ggtggacgat ggctttttgg atatctggac gtataacgct 1320
gagctgcttg ttctgctgga gaacgaaaga acccttgact accacgattc caacgtgaag 1380
aatctgtatg agaaagtgcg aagccagttg aaaaacaacg caaaagaaat aggcaacggc 1440
tgtttcgagt tctaccacaa atgcgataac acctgcatgg agagtgtgaa gaacggaacg 1500
tacgattatc caaaatactc cgaggaggcc aaactcaata gggaggagat agacggtgtt 1560
aagctggagt ccacacgcat ctatcagatt ctggcgatct actctactgt ggcttccagc 1620
ctggtgctgg tcgtttccct tggggcgatc agcttctgga tgtgcagcaa tggctccctg 1680
caatgccgca tctgcatc 1698
<210> 11
<211> 566
<212> PRT
<213> A流感病毒
<400> 11
Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Ala Thr Ala Asn
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Leu Glu Asp Lys His Asn Gly Lys Leu Cys Lys Leu Arg Gly Val
50 55 60
Ala Pro Leu His Leu Gly Lys Cys Asn Ile Ala Gly Trp Ile Leu Gly
65 70 75 80
Asn Pro Glu Cys Glu Ser Leu Ser Thr Ala Ser Ser Trp Ser Tyr Ile
85 90 95
Val Glu Thr Pro Ser Ser Asp Asn Gly Thr Cys Tyr Pro Gly Asp Phe
100 105 110
Ile Asp Tyr Glu Glu Leu Arg Glu Gln Leu Ser Ser Val Ser Ser Phe
115 120 125
Glu Arg Phe Glu Ile Phe Pro Lys Thr Ser Ser Trp Pro Asn His Asp
130 135 140
Ser Asn Lys Gly Val Thr Ala Ala Cys Pro His Ala Gly Ala Lys Ser
145 150 155 160
Phe Tyr Lys Asn Leu Ile Trp Leu Val Lys Lys Gly Asn Ser Tyr Pro
165 170 175
Lys Leu Ser Lys Ser Tyr Ile Asn Asp Lys Gly Lys Glu Val Leu Val
180 185 190
Leu Trp Gly Ile His His Pro Ser Thr Ser Ala Asp Gln Gln Ser Leu
195 200 205
Tyr Gln Asn Ala Asp Thr Tyr Val Phe Val Gly Ser Ser Arg Tyr Ser
210 215 220
Lys Lys Phe Lys Pro Glu Ile Ala Ile Arg Pro Lys Val Arg Asp Gln
225 230 235 240
Glu Gly Arg Met Asn Tyr Tyr Trp Thr Leu Val Glu Pro Gly Asp Lys
245 250 255
Ile Thr Phe Glu Ala Thr Gly Asn Leu Val Val Pro Arg Tyr Ala Phe
260 265 270
Ala Met Glu Arg Asn Ala Gly Ser Gly Ile Ile Ile Ser Asp Thr Pro
275 280 285
Val His Asp Cys Asn Thr Thr Cys Gln Thr Pro Lys Gly Ala Ile Asn
290 295 300
Thr Ser Leu Pro Phe Gln Asn Ile His Pro Ile Thr Ile Gly Lys Cys
305 310 315 320
Pro Lys Tyr Val Lys Ser Thr Lys Leu Arg Leu Ala Thr Gly Leu Arg
325 330 335
Asn Ile Pro Ser Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly
340 345 350
Phe Ile Glu Gly Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr
355 360 365
His His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser
370 375 380
Thr Gln Asn Ala Ile Asp Glu Ile Thr Asn Lys Val Asn Ser Val Ile
385 390 395 400
Glu Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn His
405 410 415
Leu Glu Lys Arg Ile Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe
420 425 430
Leu Asp Ile Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn
435 440 445
Glu Arg Thr Leu Asp Tyr His Asp Ser Asn Val Lys Asn Leu Tyr Glu
450 455 460
Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly
465 470 475 480
Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser Val
485 490 495
Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys Leu
500 505 510
Asn Arg Glu Glu Ile Asp Gly Val Lys Leu Glu Ser Thr Arg Ile Tyr
515 520 525
Gln Ile Leu Ala Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu Val
530 535 540
Val Ser Leu Gly Ala Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu
545 550 555 560
Gln Cys Arg Ile Cys Ile
565
<210> 12
<211> 1698
<212> DNA
<213> A流感病毒
<400> 12
gatgcagatg cggcattgca gggagccatt gctgcacatc cagaagctga tcgccccaag 60
ggaaacgacc agcaccaggc tggaagccac agtagagtag atcgccagaa tctgatagat 120
gcgtgtggac tccagcttaa caccgtctat ctcctcccta ttgagtttgg cctcctcgga 180
gtattttgga taatcgtacg ttccgttctt cacactctcc atgcaggtgt tatcgcattt 240
gtggtagaac tcgaaacagc cgttgcctat ttcttttgcg ttgtttttca actggcttcg 300
cactttctca tacagattct tcacgttgga atcgtggtag tcaagggttc tttcgttctc 360
cagcagaaca agcagctcag cgttatacgt ccagatatcc aaaaagccat cgtccacctt 420
cttgttcagg ttctcaattc gcttctcgag gtggttaaac tcctttccaa cagctgtgaa 480
ctgagtattc attttttcta tcacactatt gaccttgttt gtgatctcat ctatggcatt 540
ctgcgtagat ttcaggtcag cggcgtatcc ggagccctgc tcattttgat gatggtagcc 600
gtaccaaccg tccaccatcc ccgtccagcc gccttcaata aatccggcga tagcgccgaa 660
cagaccccgt gactggatgc ttgggatatt cctgagtccg gtggcgagtc tcagtttagt 720
gcttttcacg tacttggggc attttccgat tgtgattgga tgtatattct gaaagggcaa 780
gctcgtgttg atggcgccct tcggtgtctg acatgtggta ttacagtcat gaactggagt 840
gtcgctgatg ataattccgc tccccgcatt cctctccatg gcaaaagcat atctcggcac 900
gaccaggttg cccgtagcct caaacgttat cttatcgcca ggttcgacca aggtccagta 960
ataattcatc cttccttcct ggtctctcac ctttggtctg atggcgatct cgggtttgaa 1020
cttcttagaa tagcgggagc tgcccacaaa cacgtatgtg tcggcgttct gatacagaga 1080
ctgctggtcg gctgaggtag atgggtggtg tatgccccaa agcaccagaa cctctttccc 1140
tttatcgttt atgtagctct tagacagttt tgggtatgaa ttgcctttct tcacgagcca 1200
tatcaggttc ttgtagaagc ttttcgcgcc cgcatgagga caggctgcag taactccttt 1260
gttagagtca tgattgggcc aggagctagt tttcgggaaa atctcaaacc tttcgaagct 1320
gcttacggat gacaactgct ccctcagctc ttcataatca atgaagtcgc ctgggtagca 1380
ggtcccattg tcacttgacg gggtctcgac gatataggac caactggatg ccgtactcaa 1440
ggattcgcat tctggattac ccagtatcca gccggcaata ttacattttc ccagatgcag 1500
gggagccacc cctcgcagtt tgcagagctt gccattgtgt ttatcctcca gcaagttcac 1560
agagtgggtg acagtaacat tcttttcgag caccgtgtcg accgtatcgg tagagttgtt 1620
tgcatggtag ccaatacaaa gggtatcggc attggctgtg gcaaaggtgt acaggagcac 1680
gaccaaaata gccttcat 1698
<210> 13
<211> 1683
<212> DNA
<213> A流感病毒
<400> 13
atggccatca tctacctgat cctgctgttt acagctgtga gaggcgacca gatctgtatc 60
ggctaccacg ccaacaatag caccgagaag gtggacacca tcctggagag aaacgtgaca 120
gtgacccacg ccaaggacat cctggaaaag acccacaacg gcaagctgtg taagctgaac 180
ggcatccctc ctctggaact gggcgattgt tctatcgccg gatggctgct gggaaacccc 240
gagtgtgata ggctgctgtc tgtgcctgag tggagctaca tcatggagaa ggagaaccct 300
agggacggcc tgtgttaccc tggcagcttc aacgattacg aggagctgaa gcacctgctg 360
tctagcgtga agcacttcga gaaggtgaag atcctgccca aggacagatg gacccagcac 420
acaacaacag gaggaagcag agcctgcgcc gtgtctggca accccagctt cttccggaat 480
atggtgtggc tgaccaagaa gggcagcaat taccctgtgg cccagggcag ctacaataat 540
accagcggcg agcagatgct gatcatctgg ggagtgcacc accctaatga cgagaccgag 600
cagagaaccc tgtaccagaa tgtgggcacc tacgtgtctg tgggcaccag caccctgaat 660
aagagaagca cccccgagat tgccacaaga cccaaggtga acggccaggg aggaagaatg 720
gagttcagct ggaccctgct ggatatgtgg gacaccatca actttgagag caccggcaat 780
ctgatcgccc ctgagtacgg cttcaagatc agcaagagag gcagcagcgg catcatgaaa 840
accgagggca ccctggagaa ttgtgagacc aagtgccaga cacctctggg cgccatcaat 900
accaccctgc ccttccacaa tgtgcaccct ctgaccatcg gcgagtgccc taagtatgtg 960
aagagcgaga agctggtgct ggccacagga ctgagaaacg tgccccagat cgagagcaga 1020
ggcctgtttg gagccatcgc cggattcatc gagggaggat ggcagggaat ggtcgatggc 1080
tggtacggct accaccacag caatgatcag ggctctggct atgccgccga taaggagtct 1140
acccagaagg cctttgacgg catcaccaac aaggtgaaca gcgtgatcga gaagatgaac 1200
acccagtttg aggctgtggg caaggagttt agcaacctgg agcggagact ggagaacctg 1260
aacaagaaga tggaggacgg cttcctggat gtgtggacct acaatgccga actgctggtg 1320
ctgatggaga atgagcggac cctggacttc cacgacagca acgtgaagaa cctgtacgac 1380
aaagtgagga tgcagctgag ggacaacgtg aaggaactgg gcaatggctg cttcgagttc 1440
taccacaagt gtgacgacga gtgtatgaac tccgtgaaga acggcaccta cgactaccct 1500
aagtacgagg aggagagcaa gctgaaccgg aacgagatca agggcgtgaa gctgtctagc 1560
atgggcgtgt atcagatcct ggccatctat gccacagtgg ccggatctct gagcctggca 1620
attatgatgg ctggaatcag cttctggatg tgctccaatg gcagcctgca gtgccggatc 1680
tgt 1683
<210> 14
<211> 564
<212> PRT
<213> A流感病毒
<400> 14
Met Ala Ile Ile Tyr Leu Ile Leu Leu Phe Thr Ala Val Arg Gly Asp
1 5 10 15
Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Lys Val Asp
20 25 30
Thr Ile Leu Glu Arg Asn Val Thr Val Thr His Ala Lys Asp Ile Leu
35 40 45
Glu Lys Thr His Asn Gly Lys Leu Cys Lys Leu Asn Gly Ile Pro Pro
50 55 60
Leu Glu Leu Gly Asp Cys Ser Ile Ala Gly Trp Leu Leu Gly Asn Pro
65 70 75 80
Glu Cys Asp Arg Leu Leu Ser Val Pro Glu Trp Ser Tyr Ile Met Glu
85 90 95
Lys Glu Asn Pro Arg Asp Gly Leu Cys Tyr Pro Gly Ser Phe Asn Asp
100 105 110
Tyr Glu Glu Leu Lys His Leu Leu Ser Ser Val Lys His Phe Glu Lys
115 120 125
Val Lys Ile Leu Pro Lys Asp Arg Trp Thr Gln His Thr Thr Thr Gly
130 135 140
Gly Ser Arg Ala Cys Ala Val Ser Gly Asn Pro Ser Phe Phe Arg Asn
145 150 155 160
Met Val Trp Leu Thr Lys Lys Gly Ser Asn Tyr Pro Val Ala Lys Gly
165 170 175
Ser Tyr Asn Asn Thr Ser Gly Glu Gln Met Leu Ile Ile Trp Gly Val
180 185 190
His His Pro Asn Asp Glu Thr Glu Gln Arg Thr Leu Tyr Gln Asn Val
195 200 205
Gly Thr Tyr Val Ser Val Gly Thr Ser Thr Leu Asn Lys Arg Ser Thr
210 215 220
Pro Asp Tyr His Ile Ala Thr Arg Pro Lys Val Asn Gly Gln Gly Gly
225 230 235 240
Arg Met Glu Phe Ser Trp Thr Leu Leu Asp Met Trp Asp Thr Ile Asn
245 250 255
Phe Glu Ser Thr Gly Asn Leu Ile Ala Pro Glu Tyr Gly Phe Lys Ile
260 265 270
Ser Lys Arg Gly Ser Ser Gly Ile Met Lys Thr Glu Gly Thr Leu Glu
275 280 285
Asn Cys Glu Thr Lys Cys Gln Thr Pro Leu Gly Ala Ile Asn Thr Thr
290 295 300
Leu Pro Phe His Asn Val His Pro Leu Thr Ile Gly Glu Cys Pro Lys
305 310 315 320
Tyr Val Lys Ser Glu Lys Leu Val Leu Ala Thr Gly Leu Arg Asn Val
325 330 335
Pro Gln Ile Glu Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile
340 345 350
Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His His
355 360 365
Ser Asn Asp Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln
370 375 380
Lys Ala Phe Asp Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu Lys
385 390 395 400
Met Asn Thr Gln Phe Glu Ala Val Gly Lys Glu Phe Ser Asn Leu Glu
405 410 415
Arg Arg Leu Glu Asn Leu Asn Lys Lys Met Glu Asp Gly Phe Leu Asp
420 425 430
Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Met Glu Asn Glu Arg
435 440 445
Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys Val
450 455 460
Arg Met Gln Leu Arg Asp Asn Val Lys Glu Leu Gly Asn Gly Cys Phe
465 470 475 480
Glu Phe Tyr His Lys Cys Asp Asp Glu Cys Met Asn Ser Val Lys Asn
485 490 495
Gly Thr Tyr Asp Tyr Pro Lys Tyr Glu Glu Glu Ser Lys Leu Asn Arg
500 505 510
Asn Glu Ile Lys Gly Val Lys Leu Ser Ser Met Gly Val Tyr Gln Ile
515 520 525
Leu Ala Ile Tyr Ala Thr Val Ala Gly Ser Leu Ser Leu Ala Ile Met
530 535 540
Met Ala Gly Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln Cys
545 550 555 560
Arg Ile Cys Ile
<210> 15
<211> 1683
<212> DNA
<213> A流感病毒
<400> 15
acagatccgg cactgcaggc tgccattgga gcacatccag aagctgattc cagccatcat 60
aattgccagg ctcagagatc cggccactgt ggcatagatg gccaggatct gatacacgcc 120
catgctagac agcttcacgc ccttgatctc gttccggttc agcttgctct cctcctcgta 180
cttagggtag tcgtaggtgc cgttcttcac ggagttcata cactcgtcgt cacacttgtg 240
gtagaactcg aagcagccat tgcccagttc cttcacgttg tccctcagct gcatcctcac 300
tttgtcgtac aggttcttca cgttgctgtc gtggaagtcc agggtccgct cattctccat 360
cagcaccagc agttcggcat tgtaggtcca cacatccagg aagccgtcct ccatcttctt 420
gttcaggttc tccagtctcc gctccaggtt gctaaactcc ttgcccacag cctcaaactg 480
ggtgttcatc ttctcgatca cgctgttcac cttgttggtg atgccgtcaa aggccttctg 540
ggtagactcc ttatcggcgg catagccaga gccctgatca ttgctgtggt ggtagccgta 600
ccagccatcg accattccct gccatcctcc ctcgatgaat ccggcgatgg ctccaaacag 660
gcctctgctc tcgatctggg gcacgtttct cagtcctgtg gccagcacca gcttctcgct 720
cttcacatac ttagggcact cgccgatggt cagagggtgc acattgtgga agggcagggt 780
ggtattgatg gcgcccagag gtgtctggca cttggtctca caattctcca gggtgccctc 840
ggttttcatg atgccgctgc tgcctctctt gctgatcttg aagccgtact caggggcgat 900
cagattgccg gtgctctcaa agttgatggt gtcccacata tccagcaggg tccagctgaa 960
ctccattctt cctccctggc cgttcacctt gggtcttgtg gcaatctcgg gggtgcttct 1020
cttattcagg gtgctggtgc ccacagacac gtaggtgccc acattctggt acagggttct 1080
ctgctcggtc tcgtcattag ggtggtgcac tccccagatg atcagcatct gctcgccgct 1140
ggtattattg tagctgccct gggccacagg gtaattgctg cccttcttgg tcagccacac 1200
catattccgg aagaagctgg ggttgccaga cacggcgcag gctctgcttc ctcctgttgt 1260
tgtgtgctgg gtccatctgt ccttgggcag gatcttcacc ttctcgaagt gcttcacgct 1320
agacagcagg tgcttcagct cctcgtaatc gttgaagctg ccagggtaac acaggccgtc 1380
cctagggttc tccttctcca tgatgtagct ccactcaggc acagacagca gcctatcaca 1440
ctcggggttt cccagcagcc atccggcgat agaacaatcg cccagttcca gaggagggat 1500
gccgttcagc ttacacagct tgccgttgtg ggtcttttcc aggatgtcct tggcgtgggt 1560
cactgtcacg tttctctcca ggatggtgtc caccttctcg gtgctattgt tggcgtggta 1620
gccgatacag atctggtcgc ctctcacagc tgtaaacagc aggatcaggt agatgatggc 1680
cat 1683
<210> 16
<211> 1704
<212> DNA
<213> A流感病毒
<400> 16
atggaaaaga tcgtgctgct gctggccatt gtgagcctgg tgaagagcga ccagatctgc 60
attggctacc acgccaacaa tagcacagag caggtggaca ccatcatgga aaaaaacgtg 120
accgtgaccc acgctcagga catcctggaa aagacccaca acggcaagct gtgtgatctg 180
gacggcgtga agcctctgat cctgagagat tgtagcgtgg ctggatggct gctgggcaac 240
cctatgtgcg acgagttcat caacgtgccc gagtggagct atatcgtgga gaaggccaac 300
cccaccaacg atctgtgtta ccccggcagc ttcaacgatt acgaggaact gaagcacctg 360
ctgtcccgga tcaaccactt cgagaagatc cagatcatcc ccaagtcctc ttggagcgat 420
cacgaagcct ctagcggagt gtctagcgcc tgtccttacc tgggcagccc cagcttcttc 480
agaaacgtgg tgtggctgat caagaagaac agcacctacc ccaccatcaa gaagagctac 540
aacaacacca accaggaaga tctgctggtc ctgtggggaa tccaccaccc taatgatgcc 600
gccgagcaga ccagactgta ccagaacccc accacctata tcagcatcgg caccagcacc 660
ctgaatcaga gactggtgcc caagatcgcc accagatcca aggtgaacgg ccagagcggc 720
aggatggaat tcttctggac catcctgaag cccaacgacg ccatcaactt cgagagcaac 780
ggcaacttta tcgcccctga gtacgcctac aagatcgtga agaagggcga cagcgccatc 840
atgaagagcg agctggaata cggcaactgc aacaccaagt gccagacacc tatgggcgcc 900
atcaacagca gcatgccctt ccacaacatc caccctctga ccatcggcga gtgccctaag 960
tacgtgaaga gcaacagact ggtgctggcc acaggcctga gaaatagccc ccagcgggag 1020
agcagaagaa agaagagggg cctgtttgga gccatcgccg gctttattga aggcggctgg 1080
cagggaatgg tggatggctg gtacggctac caccacagca atgagcaggg ctctggatat 1140
gccgccgaca aagagtctac ccagaaggcc atcgacggcg tcaccaacaa ggtgaacagc 1200
atcatcgaca agatgaacac ccagttcgag gctgtgggca gagagttcaa caacctggaa 1260
cggcggatcg agaacctgaa caagaaaatg gaagatggct tcctggatgt gtggacctac 1320
aatgccgaac tgctggtgct gatggaaaac gagcggaccc tggacttcca cgacagcaac 1380
gtgaagaacc tgtacgacaa agtgcggctg cagctgagag acaacgccaa agagctgggc 1440
aacggctgct tcgagttcta ccacaagtgc gacaacgagt gcatggaaag catccggaac 1500
ggcacctaca actaccctca gtacagcgag gaagccaggc tgaagaggga agagatcagc 1560
ggcgtgaaac tggaatccat cggcacctac cagatcctga gcatctacag cacagtggcc 1620
tcttctctgg ccctggccat tatgatggcc ggactgagcc tgtggatgtg cagcaatggc 1680
agcctgcagt gcaggatctg catc 1704
<210> 17
<211> 568
<212> PRT
<213> A流感病毒
<400> 17
Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser
1 5 10 15
Asp Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gln Val
20 25 30
Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gln Asp Ile
35 40 45
Leu Glu Lys Thr His Asn Gly Lys Leu Cys Asp Leu Asp Gly Val Lys
50 55 60
Pro Leu Ile Leu Arg Asp Cys Ser Val Ala Gly Trp Leu Leu Gly Asn
65 70 75 80
Pro Met Cys Asp Glu Phe Ile Asn Val Pro Glu Trp Ser Tyr Ile Val
85 90 95
Glu Lys Ala Asn Pro Thr Asn Asp Leu Cys Tyr Pro Gly Ser Phe Asn
100 105 110
Asp Tyr Glu Glu Leu Lys His Leu Leu Ser Arg Ile Asn His Phe Glu
115 120 125
Lys Ile Gln Ile Ile Pro Lys Ser Ser Trp Ser Asp His Glu Ala Ser
130 135 140
Ser Gly Val Ser Ser Ala Cys Pro Tyr Leu Gly Ser Pro Ser Phe Phe
145 150 155 160
Arg Asn Val Val Trp Leu Ile Lys Lys Asn Ser Thr Tyr Pro Thr Ile
165 170 175
Lys Lys Ser Tyr Asn Asn Thr Asn Gln Glu Asp Leu Leu Val Leu Trp
180 185 190
Gly Ile His His Pro Asn Asp Ala Ala Glu Gln Thr Arg Leu Tyr Gln
195 200 205
Asn Pro Thr Thr Tyr Ile Ser Ile Gly Thr Ser Thr Leu Asn Gln Arg
210 215 220
Leu Val Pro Lys Ile Ala Thr Arg Ser Lys Val Asn Gly Gln Ser Gly
225 230 235 240
Arg Met Glu Phe Phe Trp Thr Ile Leu Lys Pro Asn Asp Ala Ile Asn
245 250 255
Phe Glu Ser Asn Gly Asn Phe Ile Ala Pro Glu Tyr Ala Tyr Lys Ile
260 265 270
Val Lys Lys Gly Asp Ser Ala Ile Met Lys Ser Glu Leu Glu Tyr Gly
275 280 285
Asn Cys Asn Thr Lys Cys Gln Thr Pro Met Gly Ala Ile Asn Ser Ser
290 295 300
Met Pro Phe His Asn Ile His Pro Leu Thr Ile Gly Glu Cys Pro Lys
305 310 315 320
Tyr Val Lys Ser Asn Arg Leu Val Leu Ala Thr Gly Leu Arg Asn Ser
325 330 335
Pro Gln Arg Glu Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile
340 345 350
Ala Gly Phe Ile Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr
355 360 365
Gly Tyr His His Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys
370 375 380
Glu Ser Thr Gln Lys Ala Ile Asp Gly Val Thr Asn Lys Val Asn Ser
385 390 395 400
Ile Ile Asp Lys Met Asn Thr Gln Phe Glu Ala Val Gly Arg Glu Phe
405 410 415
Asn Asn Leu Glu Arg Arg Ile Glu Asn Leu Asn Lys Lys Met Glu Asp
420 425 430
Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Met
435 440 445
Glu Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu
450 455 460
Tyr Asp Lys Val Arg Leu Gln Leu Arg Asp Asn Ala Lys Glu Leu Gly
465 470 475 480
Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys Met Glu
485 490 495
Ser Ile Arg Asn Gly Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu Glu Ala
500 505 510
Arg Leu Lys Arg Glu Glu Ile Ser Gly Val Lys Leu Glu Ser Ile Gly
515 520 525
Thr Tyr Gln Ile Leu Ser Ile Tyr Ser Thr Val Ala Ser Ser Leu Ala
530 535 540
Leu Ala Ile Met Met Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly
545 550 555 560
Ser Leu Gln Cys Arg Ile Cys Ile
565
<210> 18
<211> 1704
<212> DNA
<213> A流感病毒
<400> 18
gatgcagatc ctgcactgca ggctgccatt gctgcacatc cacaggctca gtccggccat 60
cataatggcc agggccagag aagaggccac tgtgctgtag atgctcagga tctggtaggt 120
gccgatggat tccagtttca cgccgctgat ctcttccctc ttcagcctgg cttcctcgct 180
gtactgaggg tagttgtagg tgccgttccg gatgctttcc atgcactcgt tgtcgcactt 240
gtggtagaac tcgaagcagc cgttgcccag ctctttggcg ttgtctctca gctgcagccg 300
cactttgtcg tacaggttct tcacgttgct gtcgtggaag tccagggtcc gctcgttttc 360
catcagcacc agcagttcgg cattgtaggt ccacacatcc aggaagccat cttccatttt 420
cttgttcagg ttctcgatcc gccgttccag gttgttgaac tctctgccca cagcctcgaa 480
ctgggtgttc atcttgtcga tgatgctgtt caccttgttg gtgacgccgt cgatggcctt 540
ctgggtagac tctttgtcgg cggcatatcc agagccctgc tcattgctgt ggtggtagcc 600
gtaccagcca tccaccattc cctgccagcc gccttcaata aagccggcga tggctccaaa 660
caggcccctc ttctttcttc tgctctcccg ctgggggcta tttctcaggc ctgtggccag 720
caccagtctg ttgctcttca cgtacttagg gcactcgccg atggtcagag ggtggatgtt 780
gtggaagggc atgctgctgt tgatggcgcc cataggtgtc tggcacttgg tgttgcagtt 840
gccgtattcc agctcgctct tcatgatggc gctgtcgccc ttcttcacga tcttgtaggc 900
gtactcaggg gcgataaagt tgccgttgct ctcgaagttg atggcgtcgt tgggcttcag 960
gatggtccag aagaattcca tcctgccgct ctggccgttc accttggatc tggtggcgat 1020
cttgggcacc agtctctgat tcagggtgct ggtgccgatg ctgatatagg tggtggggtt 1080
ctggtacagt ctggtctgct cggcggcatc attagggtgg tggattcccc acaggaccag 1140
cagatcttcc tggttggtgt tgttgtagct cttcttgatg gtggggtagg tgctgttctt 1200
cttgatcagc cacaccacgt ttctgaagaa gctggggctg cccaggtaag gacaggcgct 1260
agacactccg ctagaggctt cgtgatcgct ccaagaggac ttggggatga tctggatctt 1320
ctcgaagtgg ttgatccggg acagcaggtg cttcagttcc tcgtaatcgt tgaagctgcc 1380
ggggtaacac agatcgttgg tggggttggc cttctccacg atatagctcc actcgggcac 1440
gttgatgaac tcgtcgcaca tagggttgcc cagcagccat ccagccacgc tacaatctct 1500
caggatcaga ggcttcacgc cgtccagatc acacagcttg ccgttgtggg tcttttccag 1560
gatgtcctga gcgtgggtca cggtcacgtt tttttccatg atggtgtcca cctgctctgt 1620
gctattgttg gcgtggtagc caatgcagat ctggtcgctc ttcaccaggc tcacaatggc 1680
cagcagcagc acgatctttt ccat 1704
<210> 19
<211> 147
<212> DNA
<213> A流感病毒
<400> 19
atgaaggcca aactgctggt gctgctgtgt acctttaccg ccacctacgc cgacacaatc 60
tgtatcggct accacgccaa caatagcacc gacaccgtgg atacagtgct ggagaagaac 120
gtgaccgtga cccactctgt gaacctg 147
<210> 20
<211> 49
<212> PRT
<213> A流感病毒
<400> 20
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu
<210> 21
<211> 147
<212> DNA
<213> A流感病毒
<400> 21
caggttcaca gagtgggtca cggtcacgtt cttctccagc actgtatcca cggtgtcggt 60
gctattgttg gcgtggtagc cgatacagat tgtgtcggcg taggtggcgg taaaggtaca 120
cagcagcacc agcagtttgg ccttcat 147
<210> 22
<211> 678
<212> DNA
<213> A流感病毒
<400> 22
gatgccaagt gccagacacc tcagggcgcc atcaatagca gcctgccctt ccagaatgtg 60
caccctgtga ccatcggcga gtgccccaag tatgtgagaa gcgccaagct gagaatggtg 120
accggcctga gaaacatccc tagcatccag agcagaggac tgtttggagc catcgccgga 180
ttcatcgagg gaggatggac aggcatggtg gatggctggt acggctacca ccaccagaat 240
gagcagggct ctggatatgc cgccgatcag aagtctaccc agaacgccat caacggcatc 300
accaacaagg tgaacagcgt gatcgagaag atgaacaccc agtttaccgc tgtgggcaag 360
gagttcaaca agctggagcg gaggatggag aacctgaaca agaaggtgga cgacggcttt 420
ctggacatct ggacctacaa tgccgaactc ctggtcctcc tcgagaatga gaggaccctg 480
gacttccacg acagcaacgt gaagaacctg tatgagaagg tgaagagcca gctgaagaac 540
aacgccaagg agatcggcaa cggctgcttc gagttctacc acaagtgtaa caacgagtgt 600
atggagagcg tgaagaacgg cacctacgac taccctaagt acagcgagga gagcaagctg 660
aaccgggaga agatcgat 678
<210> 23
<211> 226
<212> PRT
<213> A流感病毒
<400> 23
Asp Ala Lys Cys Gln Thr Pro Gln Gly Ala Ile Asn Ser Ser Leu Pro
1 5 10 15
Phe Gln Asn Val His Pro Val Thr Ile Gly Glu Cys Pro Lys Tyr Val
20 25 30
Arg Ser Ala Lys Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
35 40 45
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
50 55 60
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
65 70 75 80
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
85 90 95
Ile Asn Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Asn
100 105 110
Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn Lys Leu Glu Arg Arg
115 120 125
Met Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe Leu Asp Ile Trp
130 135 140
Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn Glu Arg Thr Leu
145 150 155 160
Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys Val Lys Ser
165 170 175
Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly Cys Phe Glu Phe
180 185 190
Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser Val Lys Asn Gly Thr
195 200 205
Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu Asn Arg Glu Lys
210 215 220
Ile Asp
225
<210> 24
<211> 678
<212> DNA
<213> A流感病毒
<400> 24
atcgatcttc tcccggttca gcttgctctc ctcgctgtac ttagggtagt cgtaggtgcc 60
gttcttcacg ctctccatac actcgttgtt acacttgtgg tagaactcga agcagccgtt 120
gccgatctcc ttggcgttgt tcttcagctg gctcttcacc ttctcataca ggttcttcac 180
gttgctgtcg tggaagtcca gggtcctctc attctcgagg aggaccagga gttcggcatt 240
gtaggtccag atgtccagaa agccgtcgtc caccttcttg ttcaggttct ccatcctccg 300
ctccagcttg ttgaactcct tgcccacagc ggtaaactgg gtgttcatct tctcgatcac 360
gctgttcacc ttgttggtga tgccgttgat ggcgttctgg gtagacttct gatcggcggc 420
atatccagag ccctgctcat tctggtggtg gtagccgtac cagccatcca ccatgcctgt 480
ccatcctccc tcgatgaatc cggcgatggc tccaaacagt cctctgctct ggatgctagg 540
gatgtttctc aggccggtca ccattctcag cttggcgctt ctcacatact tggggcactc 600
gccgatggtc acagggtgca cattctggaa gggcaggctg ctattgatgg cgccctgagg 660
tgtctggcac ttggcatc 678
<210> 25
<211> 576
<212> DNA
<213> A流感病毒
<400> 25
gatgccaagt gccagacacc tcagggcgcc atcaatagca gcctgccctt ccagaatgtg 60
caccctgtga ccatcggcga gtgccccaag tatgtgagaa gcgccaagct gagaatggtg 120
accggcctga gaaacatccc tagcatccag agcagaggac tgtttggagc catcgccgga 180
ttcatcgagg gaggatggac aggcatggtg gatggctggt acggctacca ccaccagaat 240
gagcagggct ctggatatgc cgccgatcag aagtctaccc agaacgccat caacggcatc 300
accaacaagg tgaacagcgt gatcgagaag atgtacaatg ccgaactcct ggtcctcctc 360
gagaatgaga ggaccctgga cttccacgac agcaacgtga agaacctgta tgagaaggtg 420
aagagccagc tgaagaacaa cgccaaggag atcggcaacg gctgcttcga gttctaccac 480
aagtgtaaca acgagtgtat ggagagcgtg aagaacggca cctacgacta ccctaagtac 540
agcgaggaga gcaagctgaa ccgggagaag atcgat 576
<210> 26
<211> 193
<212> PRT
<213> A流感病毒
<400> 26
Asp Ala Lys Cys Gln Thr Pro Gln Gly Ala Ile Asn Ser Ser Leu Pro
1 5 10 15
Phe Gln Asn Val His Pro Val Thr Ile Gly Glu Cys Pro Lys Tyr Val
20 25 30
Arg Ser Ala Lys Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
35 40 45
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
50 55 60
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
65 70 75 80
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
85 90 95
Ile Asn Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Thr
100 105 110
Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn Glu Arg Thr Leu Asp
115 120 125
Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys Val Lys Ser Gln
130 135 140
Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly Cys Phe Glu Phe Tyr
145 150 155 160
His Lys Cys Asn Asn Glu Cys Met Glu Ser Val Lys Asn Gly Thr Tyr
165 170 175
Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu Asn Arg Glu Lys Ile
180 185 190
Asp
<210> 27
<211> 576
<212> DNA
<213> A流感病毒
<400> 27
atcgatcttc tcccggttca gcttgctctc ctcgctgtac ttagggtagt cgtaggtgcc 60
gttcttcacg ctctccatac actcgttgtt acacttgtgg tagaactcga agcagccgtt 120
gccgatctcc ttggcgttgt tcttcagctg gctcttcacc ttctcataca ggttcttcac 180
gttgctgtcg tggaagtcca gggtcctctc attctcgagg aggaccagga gttcggcatt 240
gtacatcttc tcgatcacgc tgttcacctt gttggtgatg ccgttgatgg cgttctgggt 300
agacttctga tcggcggcat atccagagcc ctgctcattc tggtggtggt agccgtacca 360
gccatccacc atgcctgtcc atcctccctc gatgaatccg gcgatggctc caaacagtcc 420
tctgctctgg atgctaggga tgtttctcag gccggtcacc attctcagct tggcgcttct 480
cacatacttg gggcactcgc cgatggtcac agggtgcaca ttctggaagg gcaggctgct 540
attgatggcg ccctgaggtg tctggcactt ggcatc 576
<210> 28
<211> 570
<212> DNA
<213> A流感病毒
<400> 28
ctgagaatgg tgaccggcct gagaaacatc cctagcatcc agagcagagg actgtttgga 60
gccatcgccg gattcatcga gggaggatgg acaggcatgg tggatggctg gtacggctac 120
caccaccaga atgagcaggg ctctggatat gccgccgatc agaagtctac ccagaacgcc 180
atcaacggca tcaccaacaa ggtgaacagc gtgatcgaga agatgaacac ccagtttacc 240
gctgtgggca aggagttcaa caagctggag cggaggatgg agaacctgaa caagaaggtg 300
gacgacggct ttctggacat ctggacctac aatgccgaac tcctggtcct cctcgagaat 360
gagaggaccc tggacttcca cgacagcaac gtgaagaacc tgtatgagaa ggtgaagagc 420
cagctgaaga acaacgccaa ggagatcggc aacggctgct tcgagttcta ccacaagtgt 480
aacaacgagt gtatggagag cgtgaagaac ggcacctacg actaccctaa gtacagcgag 540
gagagcaagc tgaaccggga gaagatcgat 570
<210> 29
<211> 194
<212> PRT
<213> A流感病毒
<400> 29
Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln Arg Glu Thr Ser
1 5 10 15
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
20 25 30
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
35 40 45
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
50 55 60
Ile Asn Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Asn
65 70 75 80
Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn Lys Leu Glu Arg Arg
85 90 95
Met Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe Leu Asp Ile Trp
100 105 110
Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn Glu Arg Thr Leu
115 120 125
Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys Val Lys Ser
130 135 140
Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly Cys Phe Glu Phe
145 150 155 160
Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser Val Lys Asn Gly Thr
165 170 175
Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu Asn Arg Glu Lys
180 185 190
Ile Asp
<210> 30
<211> 570
<212> DNA
<213> A流感病毒
<400> 30
atcgatcttc tcccggttca gcttgctctc ctcgctgtac ttagggtagt cgtaggtgcc 60
gttcttcacg ctctccatac actcgttgtt acacttgtgg tagaactcga agcagccgtt 120
gccgatctcc ttggcgttgt tcttcagctg gctcttcacc ttctcataca ggttcttcac 180
gttgctgtcg tggaagtcca gggtcctctc attctcgagg aggaccagga gttcggcatt 240
gtaggtccag atgtccagaa agccgtcgtc caccttcttg ttcaggttct ccatcctccg 300
ctccagcttg ttgaactcct tgcccacagc ggtaaactgg gtgttcatct tctcgatcac 360
gctgttcacc ttgttggtga tgccgttgat ggcgttctgg gtagacttct gatcggcggc 420
atatccagag ccctgctcat tctggtggtg gtagccgtac cagccatcca ccatgcctgt 480
ccatcctccc tcgatgaatc cggcgatggc tccaaacagt cctctgctct ggatgctagg 540
gatgtttctc aggccggtca ccattctcag 570
<210> 31
<211> 468
<212> DNA
<213> A流感病毒
<400> 31
ctgagaatgg tgaccggcct gagaaacatc cctagcatcc agagcagagg actgtttgga 60
gccatcgccg gattcatcga gggaggatgg acaggcatgg tggatggctg gtacggctac 120
caccaccaga atgagcaggg ctctggatat gccgccgatc agaagtctac ccagaacgcc 180
atcaacggca tcaccaacaa ggtgaacagc gtgatcgaga agatgtacaa tgccgaactc 240
ctggtcctcc tcgagaatga gaggaccctg gacttccacg acagcaacgt gaagaacctg 300
tatgagaagg tgaagagcca gctgaagaac aacgccaagg agatcggcaa cggctgcttc 360
gagttctacc acaagtgtaa caacgagtgt atggagagcg tgaagaacgg cacctacgac 420
taccctaagt acagcgagga gagcaagctg aaccgggaga agatcgat 468
<210> 32
<211> 157
<212> PRT
<213> A流感病毒
<400> 32
Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln Arg Glu Thr Arg
1 5 10 15
Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp Thr Gly
20 25 30
Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu Gln Gly Ser
35 40 45
Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala Ile Asn Gly Ile
50 55 60
Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Thr Tyr Asn Ala Glu
65 70 75 80
Leu Leu Val Leu Leu Glu Asn Glu Arg Thr Leu Asp Phe His Asp Ser
85 90 95
Asn Val Lys Asn Leu Tyr Glu Lys Val Lys Ser Gln Leu Lys Asn Asn
100 105 110
Ala Lys Glu Ile Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asn
115 120 125
Asn Glu Cys Met Glu Ser Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys
130 135 140
Tyr Ser Glu Glu Ser Lys Leu Asn Arg Glu Lys Ile Asp
145 150 155
<210> 33
<211> 468
<212> DNA
<213> A流感病毒
<400> 33
atcgatcttc tcccggttca gcttgctctc ctcgctgtac ttagggtagt cgtaggtgcc 60
gttcttcacg ctctccatac actcgttgtt acacttgtgg tagaactcga agcagccgtt 120
gccgatctcc ttggcgttgt tcttcagctg gctcttcacc ttctcataca ggttcttcac 180
gttgctgtcg tggaagtcca gggtcctctc attctcgagg aggaccagga gttcggcatt 240
gtacatcttc tcgatcacgc tgttcacctt gttggtgatg ccgttgatgg cgttctgggt 300
agacttctga tcggcggcat atccagagcc ctgctcattc tggtggtggt agccgtacca 360
gccatccacc atgcctgtcc atcctccctc gatgaatccg gcgatggctc caaacagtcc 420
tctgctctgg atgctaggga tgtttctcag gccggtcacc attctcag 468
<210> 34
<211> 147
<212> DNA
<213> A流感病毒
<400> 34
atgaaggcta ttttggtcgt gctcctgtac acctttgcca cagccaatgc cgataccctt 60
tgtattggct accatgcaaa caactctacc gatacggtcg acacggtgct cgaaaagaat 120
gttactgtca cccactctgt gaacttg 147
<210> 35
<211> 49
<212> PRT
<213> A流感病毒
<400> 35
Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Ala Thr Ala Asn
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu
<210> 36
<211> 147
<212> DNA
<213> A流感病毒
<400> 36
caagttcaca gagtgggtga cagtaacatt cttttcgagc accgtgtcga ccgtatcggt 60
agagttgttt gcatggtagc caatacaaag ggtatcggca ttggctgtgg caaaggtgta 120
caggagcacg accaaaatag ccttcat 147
<210> 37
<211> 672
<212> DNA
<213> A流感病毒
<400> 37
acatgtcaga caccgaaggg cgccatcaac acgagcttgc cctttcagaa tatacatcca 60
atcacaatcg gaaaatgccc caagtacgtg aaaagcacta aactgagact cgccaccgga 120
ctcaggaata tcccaagcat ccagtcacgg ggtctgttcg gcgctatcgc cggatttatt 180
gaaggcggct ggacggggat ggtggacggt tggtacggct accatcatca aaatgagcag 240
ggctccggat acgccgctga cctgaaatct acgcagaatg ccatagatga gatcacaaac 300
aaggtcaata gtgtgataga aaaaatgaat actcagttca cagctgttgg aaaggagttt 360
aaccacctcg agaagcgaat tgagaacctg aacaagaagg tggacgatgg ctttttggat 420
atctggacgt ataacgctga gctgcttgtt ctgctggaga acgaaagaac ccttgactac 480
cacgattcca acgtgaagaa tctgtatgag aaagtgcgaa gccagttgaa aaacaacgca 540
aaagaaatag gcaacggctg tttcgagttc taccacaaat gcgataacac ctgcatggag 600
agtgtgaaga acggaacgta cgattatcca aaatactccg aggaggccaa actcaatagg 660
gaggagatag ac 672
<210> 38
<211> 224
<212> PRT
<213> A流感病毒
<400> 38
Thr Cys Gln Thr Pro Lys Gly Ala Ile Asn Thr Ser Leu Pro Phe Gln
1 5 10 15
Asn Ile His Pro Ile Thr Ile Gly Lys Cys Pro Lys Tyr Val Lys Ser
20 25 30
Thr Lys Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Ser Ile Gln
35 40 45
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
50 55 60
Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu Gln
65 70 75 80
Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala Ile Asp
85 90 95
Glu Ile Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Asn Thr Gln
100 105 110
Phe Thr Ala Val Gly Lys Glu Phe Asn His Leu Glu Lys Arg Ile Glu
115 120 125
Asn Leu Asn Lys Lys Val Asp Asp Gly Phe Leu Asp Ile Trp Thr Tyr
130 135 140
Asn Ala Glu Leu Leu Val Leu Leu Glu Asn Glu Arg Thr Leu Asp Tyr
145 150 155 160
His Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys Val Arg Ser Gln Leu
165 170 175
Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly Cys Phe Glu Phe Tyr His
180 185 190
Lys Cys Asp Asn Thr Cys Met Glu Ser Val Lys Asn Gly Thr Tyr Asp
195 200 205
Tyr Pro Lys Tyr Ser Glu Glu Ala Lys Leu Asn Arg Glu Glu Ile Asp
210 215 220
<210> 39
<211> 672
<212> DNA
<213> A流感病毒
<400> 39
gtctatctcc tccctattga gtttggcctc ctcggagtat tttggataat cgtacgttcc 60
gttcttcaca ctctccatgc aggtgttatc gcatttgtgg tagaactcga aacagccgtt 120
gcctatttct tttgcgttgt ttttcaactg gcttcgcact ttctcataca gattcttcac 180
gttggaatcg tggtagtcaa gggttctttc gttctccagc agaacaagca gctcagcgtt 240
atacgtccag atatccaaaa agccatcgtc caccttcttg ttcaggttct caattcgctt 300
ctcgaggtgg ttaaactcct ttccaacagc tgtgaactga gtattcattt tttctatcac 360
actattgacc ttgtttgtga tctcatctat ggcattctgc gtagatttca ggtcagcggc 420
gtatccggag ccctgctcat tttgatgatg gtagccgtac caaccgtcca ccatccccgt 480
ccagccgcct tcaataaatc cggcgatagc gccgaacaga ccccgtgact ggatgcttgg 540
gatattcctg agtccggtgg cgagtctcag tttagtgctt ttcacgtact tggggcattt 600
tccgattgtg attggatgta tattctgaaa gggcaagctc gtgttgatgg cgcccttcgg 660
tgtctgacat gt 672
<210> 40
<211> 573
<212> DNA
<213> A流感病毒
<400> 40
acatgtcaga caccgaaggg cgccatcaac acgagcttgc cctttcagaa tatacatcca 60
atcacaatcg gaaaatgccc caagtacgtg aaaagcacta aactgagact cgccaccgga 120
ctcaggaata tcccaagcat ccagtcacgg ggtctgttcg gcgctatcgc cggatttatt 180
gaaggcggct ggacggggat ggtggacggt tggtacggct accatcatca aaatgagcag 240
ggctccggat acgccgctga cctgaaatct acgcagaatg ccatagatga gatcacaaac 300
aaggtcaata gtgtgataga aaaaatgacg tataacgctg agctgcttgt tctgctggag 360
aacgaaagaa cccttgacta ccacgattcc aacgtgaaga atctgtatga gaaagtgcga 420
agccagttga aaaacaacgc aaaagaaata ggcaacggct gtttcgagtt ctaccacaaa 480
tgcgataaca cctgcatgga gagtgtgaag aacggaacgt acgattatcc aaaatactcc 540
gaggaggcca aactcaatag ggaggagata gac 573
<210> 41
<211> 191
<212> PRT
<213> A流感病毒
<400> 41
Thr Cys Gln Thr Pro Lys Gly Ala Ile Asn Thr Ser Leu Pro Phe Gln
1 5 10 15
Asn Ile His Pro Ile Thr Ile Gly Lys Cys Pro Lys Tyr Val Lys Ser
20 25 30
Thr Lys Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Ser Ile Gln
35 40 45
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
50 55 60
Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu Gln
65 70 75 80
Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala Ile Asp
85 90 95
Glu Ile Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Thr Tyr Asn
100 105 110
Ala Glu Leu Leu Val Leu Leu Glu Asn Glu Arg Thr Leu Asp Tyr His
115 120 125
Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys Val Arg Ser Gln Leu Lys
130 135 140
Asn Asn Ala Lys Glu Ile Gly Asn Gly Cys Phe Glu Phe Tyr His Lys
145 150 155 160
Cys Asp Asn Thr Cys Met Glu Ser Val Lys Asn Gly Thr Tyr Asp Tyr
165 170 175
Pro Lys Tyr Ser Glu Glu Ala Lys Leu Asn Arg Glu Glu Ile Asp
180 185 190
<210> 42
<211> 573
<212> DNA
<213> A流感病毒
<400> 42
gtctatctcc tccctattga gtttggcctc ctcggagtat tttggataat cgtacgttcc 60
gttcttcaca ctctccatgc aggtgttatc gcatttgtgg tagaactcga aacagccgtt 120
gcctatttct tttgcgttgt ttttcaactg gcttcgcact ttctcataca gattcttcac 180
gttggaatcg tggtagtcaa gggttctttc gttctccagc agaacaagca gctcagcgtt 240
atacgtcatt ttttctatca cactattgac cttgtttgtg atctcatcta tggcattctg 300
cgtagatttc aggtcagcgg cgtatccgga gccctgctca ttttgatgat ggtagccgta 360
ccaaccgtcc accatccccg tccagccgcc ttcaataaat ccggcgatag cgccgaacag 420
accccgtgac tggatgcttg ggatattcct gagtccggtg gcgagtctca gtttagtgct 480
tttcacgtac ttggggcatt ttccgattgt gattggatgt atattctgaa agggcaagct 540
cgtgttgatg gcgcccttcg gtgtctgaca tgt 573
<210> 43
<211> 507
<212> DNA
<213> A流感病毒
<400> 43
ctgagactcg ccaccggact caggaatatc ccaagcatcc agtcacgggg tctgttcggc 60
gctatcgccg gatttattga aggcggctgg acggggatgg tggacggttg gtacggctac 120
catcatcaaa atgagcaggg ctccggatac gccgctgacc tgaaatctac gcagaatgcc 180
atagatgaga tcacaaacaa ggtcaatagt gtgatagaaa aaatgaatac tcagttcaca 240
gctgttggaa aggagtttaa ccacctcgag aagcgaattg agaacctgaa caagaaggtg 300
gacgatggct ttttggatat ctggacgtat aacgctgagc tgcttgttct gctggagaac 360
gaaagaaccc ttgactacca cgattccaac gtgaagaatc tgtatgagaa agtgcgaagc 420
cagttgaaaa acaacgcaaa agaaataggc aacggctgtt tcgagttcta ccacaaatgc 480
gataacacct gcatggagag tgtgaag 507
<210> 44
<211> 190
<212> PRT
<213> A流感病毒
<400> 44
Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Ser Ile Gln Ser Arg
1 5 10 15
Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp Thr Gly
20 25 30
Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu Gln Gly Ser
35 40 45
Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala Ile Asp Glu Ile
50 55 60
Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Asn Thr Gln Phe Thr
65 70 75 80
Ala Val Gly Lys Glu Phe Asn His Leu Glu Lys Arg Ile Glu Asn Leu
85 90 95
Asn Lys Lys Val Asp Asp Gly Phe Leu Asp Ile Trp Thr Tyr Asn Ala
100 105 110
Glu Leu Leu Val Leu Leu Glu Asn Glu Arg Thr Leu Asp Tyr His Asp
115 120 125
Ser Asn Val Lys Asn Leu Tyr Glu Lys Val Arg Ser Gln Leu Lys Asn
130 135 140
Asn Ala Lys Glu Ile Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys
145 150 155 160
Asp Asn Thr Cys Met Glu Ser Val Lys Asn Gly Thr Tyr Asp Tyr Pro
165 170 175
Lys Tyr Ser Glu Glu Ala Lys Leu Asn Arg Glu Glu Ile Asp
180 185 190
<210> 45
<211> 507
<212> DNA
<213> A流感病毒
<400> 45
cttcacactc tccatgcagg tgttatcgca tttgtggtag aactcgaaac agccgttgcc 60
tatttctttt gcgttgtttt tcaactggct tcgcactttc tcatacagat tcttcacgtt 120
ggaatcgtgg tagtcaaggg ttctttcgtt ctccagcaga acaagcagct cagcgttata 180
cgtccagata tccaaaaagc catcgtccac cttcttgttc aggttctcaa ttcgcttctc 240
gaggtggtta aactcctttc caacagctgt gaactgagta ttcatttttt ctatcacact 300
attgaccttg tttgtgatct catctatggc attctgcgta gatttcaggt cagcggcgta 360
tccggagccc tgctcatttt gatgatggta gccgtaccaa ccgtccacca tccccgtcca 420
gccgccttca ataaatccgg cgatagcgcc gaacagaccc cgtgactgga tgcttgggat 480
attcctgagt ccggtggcga gtctcag 507
<210> 46
<211> 471
<212> DNA
<213> A流感病毒
<400> 46
ctgagactcg ccaccggact caggaatatc ccaagcatcc agtcacgggg tctgttcggc 60
gctatcgccg gatttattga aggcggctgg acggggatgg tggacggttg gtacggctac 120
catcatcaaa atgagcaggg ctccggatac gccgctgacc tgaaatctac gcagaatgcc 180
atagatgaga tcacaaacaa ggtcaatagt gtgatagaaa aaatgacgta taacgctgag 240
ctgcttgttc tgctggagaa cgaaagaacc cttgactacc acgattccaa cgtgaagaat 300
ctgtatgaga aagtgcgaag ccagttgaaa aacaacgcaa aagaaatagg caacggctgt 360
ttcgagttct accacaaatg cgataacacc tgcatggaga gtgtgaagaa cggaacgtac 420
gattatccaa aatactccga ggaggccaaa ctcaataggg aggagataga c 471
<210> 47
<211> 157
<212> PRT
<213> A流感病毒
<400> 47
Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Ser Ile Gln Ser Arg
1 5 10 15
Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp Thr Gly
20 25 30
Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu Gln Gly Ser
35 40 45
Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala Ile Asp Glu Ile
50 55 60
Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Thr Tyr Asn Ala Glu
65 70 75 80
Leu Leu Val Leu Leu Glu Asn Glu Arg Thr Leu Asp Tyr His Asp Ser
85 90 95
Asn Val Lys Asn Leu Tyr Glu Lys Val Arg Ser Gln Leu Lys Asn Asn
100 105 110
Ala Lys Glu Ile Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp
115 120 125
Asn Thr Cys Met Glu Ser Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys
130 135 140
Tyr Ser Glu Glu Ala Lys Leu Asn Arg Glu Glu Ile Asp
145 150 155
<210> 48
<211> 471
<212> DNA
<213> A流感病毒
<400> 48
gtctatctcc tccctattga gtttggcctc ctcggagtat tttggataat cgtacgttcc 60
gttcttcaca ctctccatgc aggtgttatc gcatttgtgg tagaactcga aacagccgtt 120
gcctatttct tttgcgttgt ttttcaactg gcttcgcact ttctcataca gattcttcac 180
gttggaatcg tggtagtcaa gggttctttc gttctccagc agaacaagca gctcagcgtt 240
atacgtcatt ttttctatca cactattgac cttgtttgtg atctcatcta tggcattctg 300
cgtagatttc aggtcagcgg cgtatccgga gccctgctca ttttgatgat ggtagccgta 360
ccaaccgtcc accatccccg tccagccgcc ttcaataaat ccggcgatag cgccgaacag 420
accccgtgac tggatgcttg ggatattcct gagtccggtg gcgagtctca g 471
<210> 49
<211> 141
<212> DNA
<213> A流感病毒
<400> 49
atggccatca tctacctgat cctgctgttt acagctgtga gaggcgacca gatctgtatc 60
ggctaccacg ccaacaatag caccgagaag gtggacacca tcctggagag aaacgtgaca 120
gtgacccacg ccaaggacat c 141
<210> 50
<211> 47
<212> PRT
<213> A流感病毒
<400> 50
Met Ala Ile Ile Tyr Leu Ile Leu Leu Phe Thr Ala Val Arg Gly Asp
1 5 10 15
Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Lys Val Asp
20 25 30
Thr Ile Leu Glu Arg Asn Val Thr Val Thr His Ala Lys Asp Ile
35 40 45
<210> 51
<211> 141
<212> DNA
<213> A流感病毒
<400> 51
gatgtccttg gcgtgggtca ctgtcacgtt tctctccagg atggtgtcca ccttctcggt 60
gctattgttg gcgtggtagc cgatacagat ctggtcgcct ctcacagctg taaacagcag 120
gatcaggtag atgatggcca t 141
<210> 52
<211> 672
<212> DNA
<213> A流感病毒
<400> 52
aagtgccaga cacctctggg cgccatcaat accaccctgc ccttccacaa tgtgcaccct 60
ctgaccatcg gcgagtgccc taagtatgtg aagagcgaga agctggtgct ggccacagga 120
ctgagaaacg tgccccagat cgagagcaga ggcctgtttg gagccatcgc cggattcatc 180
gagggaggat ggcagggaat ggtcgatggc tggtacggct accaccacag caatgatcag 240
ggctctggct atgccgccga taaggagtct acccagaagg cctttgacgg catcaccaac 300
aaggtgaaca gcgtgatcga gaagatgaac acccagtttg aggctgtggg caaggagttt 360
agcaacctgg agcggagact ggagaacctg aacaagaaga tggaggacgg cttcctggat 420
gtgtggacct acaatgccga actgctggtg ctgatggaga atgagcggac cctggacttc 480
cacgacagca acgtgaagaa cctgtacgac aaagtgagga tgcagctgag ggacaacgtg 540
aaggaactgg gcaatggctg cttcgagttc taccacaagt gtgacgacga gtgtatgaac 600
tccgtgaaga acggcaccta cgactaccct aagtacgagg aggagagcaa gctgaaccgg 660
aacgagatca ag 672
<210> 53
<211> 224
<212> PRT
<213> A流感病毒
<400> 53
Lys Cys Gln Thr Pro Leu Gly Ala Ile Asn Thr Thr Leu Pro Phe His
1 5 10 15
Asn Val His Pro Leu Thr Ile Gly Glu Cys Pro Lys Tyr Val Lys Ser
20 25 30
Glu Lys Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu
35 40 45
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
50 55 60
Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln
65 70 75 80
Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp
85 90 95
Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Asn Thr Gln
100 105 110
Phe Glu Ala Val Gly Lys Glu Phe Ser Asn Leu Glu Arg Arg Leu Glu
115 120 125
Asn Leu Asn Lys Lys Met Glu Asp Gly Phe Leu Asp Val Trp Thr Tyr
130 135 140
Asn Ala Glu Leu Leu Val Leu Met Glu Asn Glu Arg Thr Leu Asp Phe
145 150 155 160
His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys Val Arg Met Gln Leu
165 170 175
Arg Asp Asn Val Lys Glu Leu Gly Asn Gly Cys Phe Glu Phe Tyr His
180 185 190
Lys Cys Asp Asp Glu Cys Met Asn Ser Val Lys Asn Gly Thr Tyr Asp
195 200 205
Tyr Pro Lys Tyr Glu Glu Glu Ser Lys Leu Asn Arg Asn Glu Ile Lys
210 215 220
<210> 54
<211> 672
<212> DNA
<213> A流感病毒
<400> 54
cttgatctcg ttccggttca gcttgctctc ctcctcgtac ttagggtagt cgtaggtgcc 60
gttcttcacg gagttcatac actcgtcgtc acacttgtgg tagaactcga agcagccatt 120
gcccagttcc ttcacgttgt ccctcagctg catcctcact ttgtcgtaca ggttcttcac 180
gttgctgtcg tggaagtcca gggtccgctc attctccatc agcaccagca gttcggcatt 240
gtaggtccac acatccagga agccgtcctc catcttcttg ttcaggttct ccagtctccg 300
ctccaggttg ctaaactcct tgcccacagc ctcaaactgg gtgttcatct tctcgatcac 360
gctgttcacc ttgttggtga tgccgtcaaa ggccttctgg gtagactcct tatcggcggc 420
atagccagag ccctgatcat tgctgtggtg gtagccgtac cagccatcga ccattccctg 480
ccatcctccc tcgatgaatc cggcgatggc tccaaacagg cctctgctct cgatctgggg 540
cacgtttctc agtcctgtgg ccagcaccag cttctcgctc ttcacatact tagggcactc 600
gccgatggtc agagggtgca cattgtggaa gggcagggtg gtattgatgg cgcccagagg 660
tgtctggcac tt 672
<210> 55
<211> 573
<212> DNA
<213> A流感病毒
<400> 55
aagtgccaga cacctctggg cgccatcaat accaccctgc ccttccacaa tgtgcaccct 60
ctgaccatcg gcgagtgccc taagtatgtg aagagcgaga agctggtgct ggccacagga 120
ctgagaaacg tgccccagat cgagagcaga ggcctgtttg gagccatcgc cggattcatc 180
gagggaggat ggcagggaat ggtcgatggc tggtacggct accaccacag caatgatcag 240
ggctctggct atgccgccga taaggagtct acccagaagg cctttgacgg catcaccaac 300
aaggtgaaca gcgtgatcga gaagatgacc tacaatgccg aactgctggt gctgatggag 360
aatgagcgga ccctggactt ccacgacagc aacgtgaaga acctgtacga caaagtgagg 420
atgcagctga gggacaacgt gaaggaactg ggcaatggct gcttcgagtt ctaccacaag 480
tgtgacgacg agtgtatgaa ctccgtgaag aacggcacct acgactaccc taagtacgag 540
gaggagagca agctgaaccg gaacgagatc aag 573
<210> 56
<211> 191
<212> PRT
<213> A流感病毒
<400> 56
Lys Cys Gln Thr Pro Leu Gly Ala Ile Asn Thr Thr Leu Pro Phe His
1 5 10 15
Asn Val His Pro Leu Thr Ile Gly Glu Cys Pro Lys Tyr Val Lys Ser
20 25 30
Glu Lys Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu
35 40 45
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
50 55 60
Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln
65 70 75 80
Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp
85 90 95
Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Thr Tyr Asn
100 105 110
Ala Glu Leu Leu Val Leu Met Glu Asn Glu Arg Thr Leu Asp Phe His
115 120 125
Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys Val Arg Met Gln Leu Arg
130 135 140
Asp Asn Val Lys Glu Leu Gly Asn Gly Cys Phe Glu Phe Tyr His Lys
145 150 155 160
Cys Asp Asp Glu Cys Met Asn Ser Val Lys Asn Gly Thr Tyr Asp Tyr
165 170 175
Pro Lys Tyr Glu Glu Glu Ser Lys Leu Asn Arg Asn Glu Ile Lys
180 185 190
<210> 57
<211> 573
<212> DNA
<213> A流感病毒
<400> 57
cttgatctcg ttccggttca gcttgctctc ctcctcgtac ttagggtagt cgtaggtgcc 60
gttcttcacg gagttcatac actcgtcgtc acacttgtgg tagaactcga agcagccatt 120
gcccagttcc ttcacgttgt ccctcagctg catcctcact ttgtcgtaca ggttcttcac 180
gttgctgtcg tggaagtcca gggtccgctc attctccatc agcaccagca gttcggcatt 240
gtaggtcatc ttctcgatca cgctgttcac cttgttggtg atgccgtcaa aggccttctg 300
ggtagactcc ttatcggcgg catagccaga gccctgatca ttgctgtggt ggtagccgta 360
ccagccatcg accattccct gccatcctcc ctcgatgaat ccggcgatgg ctccaaacag 420
gcctctgctc tcgatctggg gcacgtttct cagtcctgtg gccagcacca gcttctcgct 480
cttcacatac ttagggcact cgccgatggt cagagggtgc acattgtgga agggcagggt 540
ggtattgatg gcgcccagag gtgtctggca ctt 573
<210> 58
<211> 570
<212> DNA
<213> A流感病毒
<400> 58
ctggtgctgg ccacaggact gagaaacgtg ccccagatcg agagcagagg cctgtttgga 60
gccatcgccg gattcatcga gggaggatgg cagggaatgg tcgatggctg gtacggctac 120
caccacagca atgatcaggg ctctggctat gccgccgata aggagtctac ccagaaggcc 180
tttgacggca tcaccaacaa ggtgaacagc gtgatcgaga agatgaacac ccagtttgag 240
gctgtgggca aggagtttag caacctggag cggagactgg agaacctgaa caagaagatg 300
gaggacggct tcctggatgt gtggacctac aatgccgaac tgctggtgct gatggagaat 360
gagcggaccc tggacttcca cgacagcaac gtgaagaacc tgtacgacaa agtgaggatg 420
cagctgaggg acaacgtgaa ggaactgggc aatggctgct tcgagttcta ccacaagtgt 480
gacgacgagt gtatgaactc cgtgaagaac ggcacctacg actaccctaa gtacgaggag 540
gagagcaagc tgaaccggaa cgagatcaag 570
<210> 59
<211> 190
<212> PRT
<213> A流感病毒
<400> 59
Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu Ser Arg
1 5 10 15
Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp Gln Gly
20 25 30
Met Val Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln Gly Ser
35 40 45
Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp Gly Ile
50 55 60
Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Asn Thr Gln Phe Glu
65 70 75 80
Ala Val Gly Lys Glu Phe Ser Asn Leu Glu Arg Arg Leu Glu Asn Leu
85 90 95
Asn Lys Lys Met Glu Asp Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala
100 105 110
Glu Leu Leu Val Leu Met Glu Asn Glu Arg Thr Leu Asp Phe His Asp
115 120 125
Ser Asn Val Lys Asn Leu Tyr Asp Lys Val Arg Met Gln Leu Arg Asp
130 135 140
Asn Val Lys Glu Leu Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys
145 150 155 160
Asp Asp Glu Cys Met Asn Ser Val Lys Asn Gly Thr Tyr Asp Tyr Pro
165 170 175
Lys Tyr Glu Glu Glu Ser Lys Leu Asn Arg Asn Glu Ile Lys
180 185 190
<210> 60
<211> 570
<212> DNA
<213> A流感病毒
<400> 60
cttgatctcg ttccggttca gcttgctctc ctcctcgtac ttagggtagt cgtaggtgcc 60
gttcttcacg gagttcatac actcgtcgtc acacttgtgg tagaactcga agcagccatt 120
gcccagttcc ttcacgttgt ccctcagctg catcctcact ttgtcgtaca ggttcttcac 180
gttgctgtcg tggaagtcca gggtccgctc attctccatc agcaccagca gttcggcatt 240
gtaggtccac acatccagga agccgtcctc catcttcttg ttcaggttct ccagtctccg 300
ctccaggttg ctaaactcct tgcccacagc ctcaaactgg gtgttcatct tctcgatcac 360
gctgttcacc ttgttggtga tgccgtcaaa ggccttctgg gtagactcct tatcggcggc 420
atagccagag ccctgatcat tgctgtggtg gtagccgtac cagccatcga ccattccctg 480
ccatcctccc tcgatgaatc cggcgatggc tccaaacagg cctctgctct cgatctgggg 540
cacgtttctc agtcctgtgg ccagcaccag 570
<210> 61
<211> 471
<212> DNA
<213> A流感病毒
<400> 61
ctggtgctgg ccacaggact gagaaacgtg ccccagatcg agagcagagg cctgtttgga 60
gccatcgccg gattcatcga gggaggatgg cagggaatgg tcgatggctg gtacggctac 120
caccacagca atgatcaggg ctctggctat gccgccgata aggagtctac ccagaaggcc 180
tttgacggca tcaccaacaa ggtgaacagc gtgatcgaga agatgaccta caatgccgaa 240
ctgctggtgc tgatggagaa tgagcggacc ctggacttcc acgacagcaa cgtgaagaac 300
ctgtacgaca aagtgaggat gcagctgagg gacaacgtga aggaactggg caatggctgc 360
ttcgagttct accacaagtg tgacgacgag tgtatgaact ccgtgaagaa cggcacctac 420
gactacccta agtacgagga ggagagcaag ctgaaccgga acgagatcaa g 471
<210> 62
<211> 157
<212> PRT
<213> A流感病毒
<400> 62
Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu Ser Arg
1 5 10 15
Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp Gln Gly
20 25 30
Met Val Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln Gly Ser
35 40 45
Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp Gly Ile
50 55 60
Thr Asn Lys Val Asn Ser Val Ile Glu Lys Met Thr Tyr Asn Ala Glu
65 70 75 80
Leu Leu Val Leu Met Glu Asn Glu Arg Thr Leu Asp Phe His Asp Ser
85 90 95
Asn Val Lys Asn Leu Tyr Asp Lys Val Arg Met Gln Leu Arg Asp Asn
100 105 110
Val Lys Glu Leu Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp
115 120 125
Asp Glu Cys Met Asn Ser Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys
130 135 140
Tyr Glu Glu Glu Ser Lys Leu Asn Arg Asn Glu Ile Lys
145 150 155
<210> 63
<211> 471
<212> DNA
<213> A流感病毒
<400> 63
cttgatctcg ttccggttca gcttgctctc ctcctcgtac ttagggtagt cgtaggtgcc 60
gttcttcacg gagttcatac actcgtcgtc acacttgtgg tagaactcga agcagccatt 120
gcccagttcc ttcacgttgt ccctcagctg catcctcact ttgtcgtaca ggttcttcac 180
gttgctgtcg tggaagtcca gggtccgctc attctccatc agcaccagca gttcggcatt 240
gtaggtcatc ttctcgatca cgctgttcac cttgttggtg atgccgtcaa aggccttctg 300
ggtagactcc ttatcggcgg catagccaga gccctgatca ttgctgtggt ggtagccgta 360
ccagccatcg accattccct gccatcctcc ctcgatgaat ccggcgatgg ctccaaacag 420
gcctctgctc tcgatctggg gcacgtttct cagtcctgtg gccagcacca g 471
<210> 64
<211> 150
<212> DNA
<213> A流感病毒
<400> 64
gccaccatgg aaaagatcgt gctgctgctg gccattgtga gcctggtgaa gagcgaccag 60
atctgcattg gctaccacgc caacaatagc acagagcagg tggacaccat catggaaaaa 120
aacgtgaccg tgacccacgc tcaggacatc 150
<210> 65
<211> 48
<212> PRT
<213> A流感病毒
<400> 65
Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser
1 5 10 15
Asp Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gln Val
20 25 30
Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gln Asp Ile
35 40 45
<210> 66
<211> 150
<212> DNA
<213> A流感病毒
<400> 66
gatgtcctga gcgtgggtca cggtcacgtt tttttccatg atggtgtcca cctgctctgt 60
gctattgttg gcgtggtagc caatgcagat ctggtcgctc ttcaccaggc tcacaatggc 120
cagcagcagc acgatctttt ccatggtggc 150
<210> 67
<211> 681
<212> DNA
<213> A流感病毒
<400> 67
aagtgccaga cacctatggg cgccatcaac agcagcatgc ccttccacaa catccaccct 60
ctgaccatcg gcgagtgccc taagtacgtg aagagcaaca gactggtgct ggccacaggc 120
ctgagaaata gcccccagcg ggagagcaga agaaagaaga ggggcctgtt tggagccatc 180
gccggcttta ttgaaggcgg ctggcaggga atggtggatg gctggtacgg ctaccaccac 240
agcaatgagc agggctctgg atatgccgcc gacaaagagt ctacccagaa ggccatcgac 300
ggcgtcacca acaaggtgaa cagcatcatc gacaagatga acacccagtt cgaggctgtg 360
ggcagagagt tcaacaacct ggaacggcgg atcgagaacc tgaacaagaa aatggaagat 420
ggcttcctgg atgtgtggac ctacaatgcc gaactgctgg tgctgatgga aaacgagcgg 480
accctggact tccacgacag caacgtgaag aacctgtacg acaaagtgcg gctgcagctg 540
agagacaacg ccaaagagct gggcaacggc tgcttcgagt tctaccacaa gtgcgacaac 600
gagtgcatgg aaagcatccg gaacggcacc tacaactacc ctcagtacag cgaggaagcc 660
aggctgaaga gggaagagat c 681
<210> 68
<211> 227
<212> PRT
<213> A流感病毒
<400> 68
Lys Cys Gln Thr Pro Met Gly Ala Ile Asn Ser Ser Met Pro Phe His
1 5 10 15
Asn Ile His Pro Leu Thr Ile Gly Glu Cys Pro Lys Tyr Val Lys Ser
20 25 30
Asn Arg Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg Glu
35 40 45
Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile
50 55 60
Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His His
65 70 75 80
Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln
85 90 95
Lys Ala Ile Asp Gly Val Thr Asn Lys Val Asn Ser Ile Ile Asp Lys
100 105 110
Met Asn Thr Gln Phe Glu Ala Val Gly Arg Glu Phe Asn Asn Leu Glu
115 120 125
Arg Arg Ile Glu Asn Leu Asn Lys Lys Met Glu Asp Gly Phe Leu Asp
130 135 140
Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Met Glu Asn Glu Arg
145 150 155 160
Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys Val
165 170 175
Arg Leu Gln Leu Arg Asp Asn Ala Lys Glu Leu Gly Asn Gly Cys Phe
180 185 190
Glu Phe Tyr His Lys Cys Asp Asn Glu Cys Met Glu Ser Ile Arg Asn
195 200 205
Gly Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu Glu Ala Arg Leu Lys Arg
210 215 220
Glu Glu Ile
225
<210> 69
<211> 681
<212> DNA
<213> A流感病毒
<400> 69
gatctcttcc ctcttcagcc tggcttcctc gctgtactga gggtagttgt aggtgccgtt 60
ccggatgctt tccatgcact cgttgtcgca cttgtggtag aactcgaagc agccgttgcc 120
cagctctttg gcgttgtctc tcagctgcag ccgcactttg tcgtacaggt tcttcacgtt 180
gctgtcgtgg aagtccaggg tccgctcgtt ttccatcagc accagcagtt cggcattgta 240
ggtccacaca tccaggaagc catcttccat tttcttgttc aggttctcga tccgccgttc 300
caggttgttg aactctctgc ccacagcctc gaactgggtg ttcatcttgt cgatgatgct 360
gttcaccttg ttggtgacgc cgtcgatggc cttctgggta gactctttgt cggcggcata 420
tccagagccc tgctcattgc tgtggtggta gccgtaccag ccatccacca ttccctgcca 480
gccgccttca ataaagccgg cgatggctcc aaacaggccc ctcttctttc ttctgctctc 540
ccgctggggg ctatttctca ggcctgtggc cagcaccagt ctgttgctct tcacgtactt 600
agggcactcg ccgatggtca gagggtggat gttgtggaag ggcatgctgc tgttgatggc 660
gcccataggt gtctggcact t 681
<210> 70
<211> 582
<212> DNA
<213> A流感病毒
<400> 70
aagtgccaga cacctatggg cgccatcaac agcagcatgc ccttccacaa catccaccct 60
ctgaccatcg gcgagtgccc taagtacgtg aagagcaaca gactggtgct ggccacaggc 120
ctgagaaata gcccccagcg ggagagcaga agaaagaaga ggggcctgtt tggagccatc 180
gccggcttta ttgaaggcgg ctggcaggga atggtggatg gctggtacgg ctaccaccac 240
agcaatgagc agggctctgg atatgccgcc gacaaagagt ctacccagaa ggccatcgac 300
ggcgtcacca acaaggtgaa cagcatcatc gacaagatga cctacaatgc cgaactgctg 360
gtgctgatgg aaaacgagcg gaccctggac ttccacgaca gcaacgtgaa gaacctgtac 420
gacaaagtgc ggctgcagct gagagacaac gccaaagagc tgggcaacgg ctgcttcgag 480
ttctaccaca agtgcgacaa cgagtgcatg gaaagcatcc ggaacggcac ctacaactac 540
cctcagtaca gcgaggaagc caggctgaag agggaagaga tc 582
<210> 71
<211> 194
<212> PRT
<213> A流感病毒
<400> 71
Lys Cys Gln Thr Pro Met Gly Ala Ile Asn Ser Ser Met Pro Phe His
1 5 10 15
Asn Ile His Pro Leu Thr Ile Gly Glu Cys Pro Lys Tyr Val Lys Ser
20 25 30
Asn Arg Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg Glu
35 40 45
Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile
50 55 60
Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His His
65 70 75 80
Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln
85 90 95
Lys Ala Ile Asp Gly Val Thr Asn Lys Val Asn Ser Ile Ile Asp Lys
100 105 110
Met Thr Tyr Asn Ala Glu Leu Leu Val Leu Met Glu Asn Glu Arg Thr
115 120 125
Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys Val Arg
130 135 140
Leu Gln Leu Arg Asp Asn Ala Lys Glu Leu Gly Asn Gly Cys Phe Glu
145 150 155 160
Phe Tyr His Lys Cys Asp Asn Glu Cys Met Glu Ser Ile Arg Asn Gly
165 170 175
Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu Glu Ala Arg Leu Lys Arg Glu
180 185 190
Glu Ile
<210> 72
<211> 582
<212> DNA
<213> A流感病毒
<400> 72
gatctcttcc ctcttcagcc tggcttcctc gctgtactga gggtagttgt aggtgccgtt 60
ccggatgctt tccatgcact cgttgtcgca cttgtggtag aactcgaagc agccgttgcc 120
cagctctttg gcgttgtctc tcagctgcag ccgcactttg tcgtacaggt tcttcacgtt 180
gctgtcgtgg aagtccaggg tccgctcgtt ttccatcagc accagcagtt cggcattgta 240
ggtcatcttg tcgatgatgc tgttcacctt gttggtgacg ccgtcgatgg ccttctgggt 300
agactctttg tcggcggcat atccagagcc ctgctcattg ctgtggtggt agccgtacca 360
gccatccacc attccctgcc agccgccttc aataaagccg gcgatggctc caaacaggcc 420
cctcttcttt cttctgctct cccgctgggg gctatttctc aggcctgtgg ccagcaccag 480
tctgttgctc ttcacgtact tagggcactc gccgatggtc agagggtgga tgttgtggaa 540
gggcatgctg ctgttgatgg cgcccatagg tgtctggcac tt 582
<210> 73
<211> 579
<212> DNA
<213> A流感病毒
<400> 73
ctggtgctgg ccacaggcct gagaaatagc ccccagcggg agagcagaag aaagaagagg 60
ggcctgtttg gagccatcgc cggctttatt gaaggcggct ggcagggaat ggtggatggc 120
tggtacggct accaccacag caatgagcag ggctctggat atgccgccga caaagagtct 180
acccagaagg ccatcgacgg cgtcaccaac aaggtgaaca gcatcatcga caagatgaac 240
acccagttcg aggctgtggg cagagagttc aacaacctgg aacggcggat cgagaacctg 300
aacaagaaaa tggaagatgg cttcctggat gtgtggacct acaatgccga actgctggtg 360
ctgatggaaa acgagcggac cctggacttc cacgacagca acgtgaagaa cctgtacgac 420
aaagtgcggc tgcagctgag agacaacgcc aaagagctgg gcaacggctg cttcgagttc 480
taccacaagt gcgacaacga gtgcatggaa agcatccgga acggcaccta caactaccct 540
cagtacagcg aggaagccag gctgaagagg gaagagatc 579
<210> 74
<211> 193
<212> PRT
<213> A流感病毒
<400> 74
Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg Glu Ser Arg
1 5 10 15
Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
20 25 30
Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Ser Asn
35 40 45
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala
50 55 60
Ile Asp Gly Val Thr Asn Lys Val Asn Ser Ile Ile Asp Lys Met Asn
65 70 75 80
Thr Gln Phe Glu Ala Val Gly Arg Glu Phe Asn Asn Leu Glu Arg Arg
85 90 95
Ile Glu Asn Leu Asn Lys Lys Met Glu Asp Gly Phe Leu Asp Val Trp
100 105 110
Thr Tyr Asn Ala Glu Leu Leu Val Leu Met Glu Asn Glu Arg Thr Leu
115 120 125
Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys Val Arg Leu
130 135 140
Gln Leu Arg Asp Asn Ala Lys Glu Leu Gly Asn Gly Cys Phe Glu Phe
145 150 155 160
Tyr His Lys Cys Asp Asn Glu Cys Met Glu Ser Ile Arg Asn Gly Thr
165 170 175
Tyr Asn Tyr Pro Gln Tyr Ser Glu Glu Ala Arg Leu Lys Arg Glu Glu
180 185 190
Ile
<210> 75
<211> 579
<212> DNA
<213> A流感病毒
<400> 75
gatctcttcc ctcttcagcc tggcttcctc gctgtactga gggtagttgt aggtgccgtt 60
ccggatgctt tccatgcact cgttgtcgca cttgtggtag aactcgaagc agccgttgcc 120
cagctctttg gcgttgtctc tcagctgcag ccgcactttg tcgtacaggt tcttcacgtt 180
gctgtcgtgg aagtccaggg tccgctcgtt ttccatcagc accagcagtt cggcattgta 240
ggtccacaca tccaggaagc catcttccat tttcttgttc aggttctcga tccgccgttc 300
caggttgttg aactctctgc ccacagcctc gaactgggtg ttcatcttgt cgatgatgct 360
gttcaccttg ttggtgacgc cgtcgatggc cttctgggta gactctttgt cggcggcata 420
tccagagccc tgctcattgc tgtggtggta gccgtaccag ccatccacca ttccctgcca 480
gccgccttca ataaagccgg cgatggctcc aaacaggccc ctcttctttc ttctgctctc 540
ccgctggggg ctatttctca ggcctgtggc cagcaccag 579
<210> 76
<211> 480
<212> DNA
<213> A流感病毒
<400> 76
ctggtgctgg ccacaggcct gagaaatagc ccccagcggg agagcagaag aaagaagagg 60
ggcctgtttg gagccatcgc cggctttatt gaaggcggct ggcagggaat ggtggatggc 120
tggtacggct accaccacag caatgagcag ggctctggat atgccgccga caaagagtct 180
acccagaagg ccatcgacgg cgtcaccaac aaggtgaaca gcatcatcga caagatgacc 240
tacaatgccg aactgctggt gctgatggaa aacgagcgga ccctggactt ccacgacagc 300
aacgtgaaga acctgtacga caaagtgcgg ctgcagctga gagacaacgc caaagagctg 360
ggcaacggct gcttcgagtt ctaccacaag tgcgacaacg agtgcatgga aagcatccgg 420
aacggcacct acaactaccc tcagtacagc gaggaagcca ggctgaagag ggaagagatc 480
<210> 77
<211> 160
<212> PRT
<213> A流感病毒
<400> 77
Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg Glu Ser Arg
1 5 10 15
Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
20 25 30
Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Ser Asn
35 40 45
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala
50 55 60
Ile Asp Gly Val Thr Asn Lys Val Asn Ser Ile Ile Asp Lys Met Thr
65 70 75 80
Tyr Asn Ala Glu Leu Leu Val Leu Met Glu Asn Glu Arg Thr Leu Asp
85 90 95
Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys Val Arg Leu Gln
100 105 110
Leu Arg Asp Asn Ala Lys Glu Leu Gly Asn Gly Cys Phe Glu Phe Tyr
115 120 125
His Lys Cys Asp Asn Glu Cys Met Glu Ser Ile Arg Asn Gly Thr Tyr
130 135 140
Asn Tyr Pro Gln Tyr Ser Glu Glu Ala Arg Leu Lys Arg Glu Glu Ile
145 150 155 160
<210> 78
<211> 480
<212> DNA
<213> A流感病毒
<400> 78
gatctcttcc ctcttcagcc tggcttcctc gctgtactga gggtagttgt aggtgccgtt 60
ccggatgctt tccatgcact cgttgtcgca cttgtggtag aactcgaagc agccgttgcc 120
cagctctttg gcgttgtctc tcagctgcag ccgcactttg tcgtacaggt tcttcacgtt 180
gctgtcgtgg aagtccaggg tccgctcgtt ttccatcagc accagcagtt cggcattgta 240
ggtcatcttg tcgatgatgc tgttcacctt gttggtgacg ccgtcgatgg ccttctgggt 300
agactctttg tcggcggcat atccagagcc ctgctcattg ctgtggtggt agccgtacca 360
gccatccacc attccctgcc agccgccttc aataaagccg gcgatggctc caaacaggcc 420
cctcttcttt cttctgctct cccgctgggg gctatttctc aggcctgtgg ccagcaccag 480
<210> 79
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 79
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 80
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 80
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 81
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 81
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 82
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 82
atgaaggcaa tcctggtcgt cctgctgtat actttcgcta ccgctaacgc tgacaccctg 60
tgcatcggct atcacgctaa caactcaacc gacacagtgg atactgtcct ggagaagaac 120
gtgactgtca cccactctgt gaatctgggc agtggactga ggctggcaac tggactgcga 180
aacatcccac agcgggaaac cagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaacga gcagggatca 300
ggctacgccg ctgacctgaa gagcacacag aatgcaatcg atgaaattac taacatggtg 360
aattccgtca tcgagaaaat gggcagcgga ggctccggaa ccgacctggc agaactgctg 420
gtgctgctgc tgaaccagtg gacactgctg taccacgata gtaacgtgaa gaatctgtat 480
gagaaagtcc gatcacagct gaagaacaat gctaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcgacaa cacctgtatg gagagcgtga aaaatggcac atacgattat 600
cccaagtatt ccgaggaagc caaactgaac agagaggaaa ttgac 645
<210> 83
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 83
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asp Glu Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Tyr His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys
195 200 205
Leu Asn Arg Glu Glu Ile Asp
210 215
<210> 84
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 84
gtcaatttcc tctctgttca gtttggcttc ctcggaatac ttgggataat cgtatgtgcc 60
atttttcacg ctctccatac aggtgttgtc gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttagcattgt tcttcagctg tgatcggact ttctcataca gattcttcac 180
gttactatcg tggtacagca gtgtccactg gttcagcagc agcaccagca gttctgccag 240
gtcggttccg gagcctccgc tgcccatttt ctcgatgacg gaattcacca tgttagtaat 300
ttcatcgatt gcattctgtg tgctcttcag gtcagcggcg tagcctgatc cctgctcgtt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctctggtttc ccgctgtggg atgtttcgca gtccagttgc 480
cagcctcagt ccactgccca gattcacaga gtgggtgaca gtcacgttct tctccaggac 540
agtatccact gtgtcggttg agttgttagc gtgatagccg atgcacaggg tgtcagcgtt 600
agcggtagcg aaagtataca gcaggacgac caggattgcc ttcat 645
<210> 85
<211> 639
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 85
atggctatca tctacctgat cctgctgttc actgctgtgc ggggggacca gatttgcatc 60
ggctaccacg ctaataattc aactgagaag gtggatacta tcctggagcg gaacgtgacc 120
gtcacacacg ctaaagacat tggcagcgga ctggtgctgg caaccggact gaggaatgtc 180
ccacagatcg agtcccgcgg actgttcggc gctatcgcag ggtttattga aggcgggtgg 240
cagggaatga ttgatgggtg gtacggctac caccattcta acgaccaagg aagtggctac 300
gccgctgata aggagagtac tcagaaagcc ttcgatggca tcaccaacat ggtgaattca 360
gtcattgaga agatgggcag cggaggctcc ggaaccgacc tggcagaact gctggtgctg 420
ctgctgaatc agtggacact gctgtttcac gactctaacg tgaagaatct gtatgataaa 480
gtccggatgc agctgagaga caacgtgaag gagctgggga atggatgctt cgaattttac 540
cataagtgcg acgatgagtg tatgaacagt gtcaaaaatg gcacatacga ttatcccaag 600
tatgaggaag agtcaaaact gaaccgaaat gaaatcaag 639
<210> 86
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 86
Met Ala Ile Ile Tyr Leu Ile Leu Leu Phe Thr Ala Val Arg Gly Asp
1 5 10 15
Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Lys Val Asp
20 25 30
Thr Ile Leu Glu Arg Asn Val Thr Val Thr His Ala Lys Asp Ile Gly
35 40 45
Ser Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu
50 55 60
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
65 70 75 80
Gln Gly Met Ile Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln
85 90 95
Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp
100 105 110
Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser Gly
115 120 125
Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn Gln
130 135 140
Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys
145 150 155 160
Val Arg Met Gln Leu Arg Asp Asn Val Lys Glu Leu Gly Asn Gly Cys
165 170 175
Phe Glu Phe Tyr His Lys Cys Asp Asp Glu Cys Met Asn Ser Val Lys
180 185 190
Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Glu Glu Glu Ser Lys Leu Asn
195 200 205
Arg Asn Glu Ile Lys
210
<210> 87
<211> 639
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 87
cttgatttca tttcggttca gttttgactc ttcctcatac ttgggataat cgtatgtgcc 60
atttttgaca ctgttcatac actcatcgtc gcacttatgg taaaattcga agcatccatt 120
ccccagctcc ttcacgttgt ctctcagctg catccggact ttatcataca gattcttcac 180
gttagagtcg tgaaacagca gtgtccactg attcagcagc agcaccagca gttctgccag 240
gtcggttccg gagcctccgc tgcccatctt ctcaatgact gaattcacca tgttggtgat 300
gccatcgaag gctttctgag tactctcctt atcagcggcg tagccacttc cttggtcgtt 360
agaatggtgg tagccgtacc acccatcaat cattccctgc cacccgcctt caataaaccc 420
tgcgatagcg ccgaacagtc cgcgggactc gatctgtggg acattcctca gtccggttgc 480
cagcaccagt ccgctgccaa tgtctttagc gtgtgtgacg gtcacgttcc gctccaggat 540
agtatccacc ttctcagttg aattattagc gtggtagccg atgcaaatct ggtccccccg 600
cacagcagtg aacagcagga tcaggtagat gatagccat 639
<210> 88
<211> 651
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 88
atggaaaaaa tcgtgctgct gctggctatc gtgtccctgg tgaagtccga ccagatctgt 60
attgggtatc atgctaacaa ctccacagaa caggtggata ctatcatgga gaagaacgtg 120
accgtcacac acgctcagga cattggatgg ggactggtcc tggcaaccgg actgagaaat 180
tcaccacaga gggaaagccg gagaaagaaa cgcggactgt tcggcgctat cgcagggttt 240
attgagggcg ggtggcaggg aatggtggat gggtggtacg gctaccacca ttccaacgaa 300
cagggatctg gctacgccgc tgataaggag tctactcaga aagctatcga cggcgtgacc 360
aacatggtca atagtatcat tgataagatg ggctctggag gcagtggaac cgacctggca 420
gagctgctgg tgctgctgct gaaccagtgg acactgctgt tccacgactc taacgtgaag 480
aatctgtatg ataaagtccg actgcagctg cgggacaacg ccaaggaact ggggaatgga 540
tgcttcgagt tctaccataa gtgcgataac gaatgtatgg agagcatccg aaacggcaca 600
tacaattatc cccagtattc cgaggaagct aggctgaaac gcgaggaaat t 651
<210> 89
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 89
Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser
1 5 10 15
Asp Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gln Val
20 25 30
Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gln Asp Ile
35 40 45
Gly Trp Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg
50 55 60
Glu Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe
65 70 75 80
Ile Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His
85 90 95
His Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr
100 105 110
Gln Lys Ala Ile Asp Gly Val Thr Asn Met Val Asn Ser Ile Ile Asp
115 120 125
Lys Met Gly Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val
130 135 140
Leu Leu Leu Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys
145 150 155 160
Asn Leu Tyr Asp Lys Val Arg Leu Gln Leu Arg Asp Asn Ala Lys Glu
165 170 175
Leu Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys
180 185 190
Met Glu Ser Ile Arg Asn Gly Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu
195 200 205
Glu Ala Arg Leu Lys Arg Glu Glu Ile
210 215
<210> 90
<211> 651
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 90
aatttcctcg cgtttcagcc tagcttcctc ggaatactgg ggataattgt atgtgccgtt 60
tcggatgctc tccatacatt cgttatcgca cttatggtag aactcgaagc atccattccc 120
cagttccttg gcgttgtccc gcagctgcag tcggacttta tcatacagat tcttcacgtt 180
agagtcgtgg aacagcagtg tccactggtt cagcagcagc accagcagct ctgccaggtc 240
ggttccactg cctccagagc ccatcttatc aatgatacta ttgaccatgt tggtcacgcc 300
gtcgatagct ttctgagtag actccttatc agcggcgtag ccagatccct gttcgttgga 360
atggtggtag ccgtaccacc catccaccat tccctgccac ccgccctcaa taaaccctgc 420
gatagcgccg aacagtccgc gtttctttct ccggctttcc ctctgtggtg aatttctcag 480
tccggttgcc aggaccagtc cccatccaat gtcctgagcg tgtgtgacgg tcacgttctt 540
ctccatgata gtatccacct gttctgtgga gttgttagca tgatacccaa tacagatctg 600
gtcggacttc accagggaca cgatagccag cagcagcacg attttttcca t 651
<210> 91
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 91
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 92
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 92
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 93
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 93
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 94
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 94
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccattct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgatgc tgaaccagtt cactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 95
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 95
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Ile Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Met Leu
130 135 140
Asn Gln Phe Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 96
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 96
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtgaactg gttcagcatc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccagaat 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 97
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 97
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcaatgga acaggcggag ctgacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 98
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 98
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Asn Gly Thr Gly Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 99
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 99
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtcagctccg cctgttccat tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 100
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 100
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcggaaat ggcactggag ctgacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 101
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 101
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 102
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 102
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtcagctcca gtgccatttc cgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 103
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 103
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggcaacggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 104
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 104
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Asn Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 105
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 105
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtctgttccg ttgcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 106
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 106
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 107
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 107
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 108
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 108
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaac agcagagtcc actggttcag 720
cagcagcacc agcagctcag ccaggtctgt tccggagcct ccgctgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 109
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 109
atgaaggcaa tcctggtcgt cctgctgtat actttcgcta ccgctaacgc tgacaccctg 60
tgcatcggct atcacgctaa caactcaacc gacacagtgg atactgtcct ggagaagaac 120
gtgactgtca cccactctgt gaatctgggc agtggactga ggctggcaac tggactgcga 180
aacatcccac agcgggaaac cagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaacga gcagggatca 300
ggctacgccg ctgacctgaa gagcacacag aatgcaatcg atgaaattac taacatggtg 360
aattccgtca tcgagaaaat gggcagcgga ggctccggaa ccgacctggc agaactgctg 420
gtgctgctgc tgaaccagtg gacactgctg taccacgata gtaacgtgaa gaatctgtat 480
gagaaagtcc gatcacagct gaagaacaat gctaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcgacaa cacctgtatg gagagcgtga aaaatggcac atacgattat 600
cccaagtatt ccgaggaagc caaactgaac agagaggaaa ttgactctgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtcaacaag gagatgcaga gctccaatct gtacatgtcc 720
atgtctagtt ggtgttatac ccactctctg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaacga gaacaatgtg 840
cccgtccagc tgacatcaat cagcgcccct gaacataagt tcgagggcct gactcagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagtaaaga tcatgctacc ttcaattttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gagccggaaa 1140
agtgggtca 1149
<210> 110
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 110
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asp Glu Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Tyr His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 111
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 111
tgacccactt ttccggctct tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaaattgaag gtagcatgat ctttactctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgagtca ggccctcgaa cttatgttca ggggcgctga ttgatgtcag 300
ctggacgggc acattgttct cgttcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agagagtggg tataacacca 420
actagacatg gacatgtaca gattggagct ctgcatctcc ttgttgacct gttcgttcag 480
cagcttgatg atgtcgcccc cagagtcaat ttcctctctg ttcagtttgg cttcctcgga 540
atacttggga taatcgtatg tgccattttt cacgctctcc atacaggtgt tgtcgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttagca ttgttcttca gctgtgatcg 660
gactttctca tacagattct tcacgttact atcgtggtac agcagtgtcc actggttcag 720
cagcagcacc agcagttctg ccaggtcggt tccggagcct ccgctgccca ttttctcgat 780
gacggaattc accatgttag taatttcatc gattgcattc tgtgtgctct tcaggtcagc 840
ggcgtagcct gatccctgct cgttctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctctgg tttcccgctg 960
tgggatgttt cgcagtccag ttgccagcct cagtccactg cccagattca cagagtgggt 1020
gacagtcacg ttcttctcca ggacagtatc cactgtgtcg gttgagttgt tagcgtgata 1080
gccgatgcac agggtgtcag cgttagcggt agcgaaagta tacagcagga cgaccaggat 1140
tgccttcat 1149
<210> 112
<211> 1143
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 112
atggctatca tctacctgat cctgctgttc actgctgtgc ggggggacca gatttgcatc 60
ggctaccacg ctaataattc aactgagaag gtggatacta tcctggagcg gaacgtgacc 120
gtcacacacg ctaaagacat tggcagcgga ctggtgctgg caaccggact gaggaatgtc 180
ccacagatcg agtcccgcgg actgttcggc gctatcgcag ggtttattga aggcgggtgg 240
cagggaatga ttgatgggtg gtacggctac caccattcta acgaccaagg aagtggctac 300
gccgctgata aggagagtac tcagaaagcc ttcgatggca tcaccaacat ggtgaattca 360
gtcattgaga agatgggcag cggaggctcc ggaaccgacc tggcagaact gctggtgctg 420
ctgctgaatc agtggacact gctgtttcac gactctaacg tgaagaatct gtatgataaa 480
gtccggatgc agctgagaga caacgtgaag gagctgggga atggatgctt cgaattttac 540
cataagtgcg acgatgagtg tatgaacagt gtcaaaaatg gcacatacga ttatcccaag 600
tatgaggaag agtcaaaact gaaccgaaat gaaatcaaga gcgggggcga catcatcaag 660
ctgctgaacg agcaagtgaa taaggaaatg cagagctcca acctgtacat gtccatgtct 720
agttggtgtt atactcactc tctggatggc gccgggctgt tcctgtttga ccacgcagcc 780
gaagagtacg agcatgctaa gaaactgatc attttcctga acgaaaacaa cgtgcccgtc 840
cagctgacat caatcagcgc acctgagcat aagttcgaag gcctgactca gatctttcag 900
aaagcttacg agcacgaaca gcatatttcc gagtctatca acaatattgt ggaccacgcc 960
atcaagagca aagatcatgc taccttcaac tttctgcagt ggtacgtggc cgagcagcac 1020
gaagaggaag tcctgtttaa ggacatcctg gataaaatcg agctgattgg aaacgaaaat 1080
catggcctgt acctggcaga ccagtatgtg aagggcattg ccaagtccag aaaaagtggg 1140
tca 1143
<210> 113
<211> 381
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 113
Met Ala Ile Ile Tyr Leu Ile Leu Leu Phe Thr Ala Val Arg Gly Asp
1 5 10 15
Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Lys Val Asp
20 25 30
Thr Ile Leu Glu Arg Asn Val Thr Val Thr His Ala Lys Asp Ile Gly
35 40 45
Ser Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu
50 55 60
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
65 70 75 80
Gln Gly Met Ile Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln
85 90 95
Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp
100 105 110
Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser Gly
115 120 125
Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn Gln
130 135 140
Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys
145 150 155 160
Val Arg Met Gln Leu Arg Asp Asn Val Lys Glu Leu Gly Asn Gly Cys
165 170 175
Phe Glu Phe Tyr His Lys Cys Asp Asp Glu Cys Met Asn Ser Val Lys
180 185 190
Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Glu Glu Glu Ser Lys Leu Asn
195 200 205
Arg Asn Glu Ile Lys Ser Gly Gly Asp Ile Ile Lys Leu Leu Asn Glu
210 215 220
Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser Met Ser
225 230 235 240
Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe Leu Phe
245 250 255
Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile Ile Phe
260 265 270
Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser Ala Pro
275 280 285
Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala Tyr Glu
290 295 300
His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp His Ala
305 310 315 320
Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp Tyr Val
325 330 335
Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu Asp Lys
340 345 350
Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala Asp Gln
355 360 365
Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 114
<211> 1143
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 114
tgacccactt tttctggact tggcaatgcc cttcacatac tggtctgcca ggtacaggcc 60
atgattttcg tttccaatca gctcgatttt atccaggatg tccttaaaca ggacttcctc 120
ttcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
gatggcgtgg tccacaatat tgttgataga ctcggaaata tgctgttcgt gctcgtaagc 240
tttctgaaag atctgagtca ggccttcgaa cttatgctca ggtgcgctga ttgatgtcag 300
ctggacgggc acgttgtttt cgttcaggaa aatgatcagt ttcttagcat gctcgtactc 360
ttcggctgcg tggtcaaaca ggaacagccc ggcgccatcc agagagtgag tataacacca 420
actagacatg gacatgtaca ggttggagct ctgcatttcc ttattcactt gctcgttcag 480
cagcttgatg atgtcgcccc cgctcttgat ttcatttcgg ttcagttttg actcttcctc 540
atacttggga taatcgtatg tgccattttt gacactgttc atacactcat cgtcgcactt 600
atggtaaaat tcgaagcatc cattccccag ctccttcacg ttgtctctca gctgcatccg 660
gactttatca tacagattct tcacgttaga gtcgtgaaac agcagtgtcc actgattcag 720
cagcagcacc agcagttctg ccaggtcggt tccggagcct ccgctgccca tcttctcaat 780
gactgaattc accatgttgg tgatgccatc gaaggctttc tgagtactct ccttatcagc 840
ggcgtagcca cttccttggt cgttagaatg gtggtagccg taccacccat caatcattcc 900
ctgccacccg ccttcaataa accctgcgat agcgccgaac agtccgcggg actcgatctg 960
tgggacattc ctcagtccgg ttgccagcac cagtccgctg ccaatgtctt tagcgtgtgt 1020
gacggtcacg ttccgctcca ggatagtatc caccttctca gttgaattat tagcgtggta 1080
gccgatgcaa atctggtccc cccgcacagc agtgaacagc aggatcaggt agatgatagc 1140
cat 1143
<210> 115
<211> 1158
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 115
atggaaaaaa tcgtgctgct gctggctatc gtgtccctgg tgaagtccga ccagatctgt 60
attgggtatc atgctaacaa ctccacagaa caggtggata ctatcatgga gaagaacgtg 120
accgtcacac acgctcagga cattggatgg ggactggtcc tggcaaccgg actgagaaat 180
tcaccacaga gggaaagccg gagaaagaaa cgcggactgt tcggcgctat cgcagggttt 240
attgagggcg ggtggcaggg aatggtggat gggtggtacg gctaccacca ttccaacgaa 300
cagggatctg gctacgccgc tgataaggag tctactcaga aagctatcga cggcgtgacc 360
aacatggtca atagtatcat tgataagatg ggctctggag gcagtggaac cgacctggca 420
gagctgctgg tgctgctgct gaaccagtgg acactgctgt tccacgactc taacgtgaag 480
aatctgtatg ataaagtccg actgcagctg cgggacaacg ccaaggaact ggggaatgga 540
tgcttcgagt tctaccataa gtgcgataac gaatgtatgg agagcatccg aaacggcaca 600
tacaattatc cccagtattc cgaggaagct aggctgaaac gcgaggaaat tagctccggg 660
ggagacatca ttaagctgct gaacgaacag gtgaacaagg agatgcagtc tagtaacctg 720
tacatgagta tgtcaagctg gtgttatact cactcactgg atggcgccgg gctgttcctg 780
tttgaccacg cagccgagga atacgaacat gctaagaaac tgatcatttt cctgaatgag 840
aacaatgtgc ccgtccagct gacatccatc tctgcacctg aacataagtt cgagggcctg 900
actcagatct ttcagaaagc ctacgaacac gagcagcata ttagtgagtc aatcaacaat 960
attgtggacc acgccatcaa gagcaaagat catgctacct tcaattttct gcagtggtac 1020
gtggccgagc agcacgagga agaggtcctg tttaaggaca tcctggataa aatcgaactg 1080
attggaaacg agaatcatgg cctgtacctg gcagaccagt atgtgaaggg cattgccaag 1140
tccaggaaaa gcgggtcc 1158
<210> 116
<211> 386
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 116
Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser
1 5 10 15
Asp Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gln Val
20 25 30
Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gln Asp Ile
35 40 45
Gly Trp Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg
50 55 60
Glu Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe
65 70 75 80
Ile Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His
85 90 95
His Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr
100 105 110
Gln Lys Ala Ile Asp Gly Val Thr Asn Met Val Asn Ser Ile Ile Asp
115 120 125
Lys Met Gly Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val
130 135 140
Leu Leu Leu Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys
145 150 155 160
Asn Leu Tyr Asp Lys Val Arg Leu Gln Leu Arg Asp Asn Ala Lys Glu
165 170 175
Leu Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys
180 185 190
Met Glu Ser Ile Arg Asn Gly Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu
195 200 205
Glu Ala Arg Leu Lys Arg Glu Glu Ile Ser Ser Gly Gly Asp Ile Ile
210 215 220
Lys Leu Leu Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu
225 230 235 240
Tyr Met Ser Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala
245 250 255
Gly Leu Phe Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys
260 265 270
Lys Leu Ile Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr
275 280 285
Ser Ile Ser Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe
290 295 300
Gln Lys Ala Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn
305 310 315 320
Ile Val Asp His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe
325 330 335
Leu Gln Trp Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys
340 345 350
Asp Ile Leu Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu
355 360 365
Tyr Leu Ala Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser
370 375 380
Gly Ser
385
<210> 117
<211> 1158
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 117
ggacccgctt ttcctggact tggcaatgcc cttcacatac tggtctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcttc 120
ctcgtgctgc tcggccacgt accactgcag aaaattgaag gtagcatgat ctttgctctt 180
gatggcgtgg tccacaatat tgttgattga ctcactaata tgctgctcgt gttcgtaggc 240
tttctgaaag atctgagtca ggccctcgaa cttatgttca ggtgcagaga tggatgtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttcttagcat gttcgtattc 360
ctcggctgcg tggtcaaaca ggaacagccc ggcgccatcc agtgagtgag tataacacca 420
gcttgacata ctcatgtaca ggttactaga ctgcatctcc ttgttcacct gttcgttcag 480
cagcttaatg atgtctcccc cggagctaat ttcctcgcgt ttcagcctag cttcctcgga 540
atactgggga taattgtatg tgccgtttcg gatgctctcc atacattcgt tatcgcactt 600
atggtagaac tcgaagcatc cattccccag ttccttggcg ttgtcccgca gctgcagtcg 660
gactttatca tacagattct tcacgttaga gtcgtggaac agcagtgtcc actggttcag 720
cagcagcacc agcagctctg ccaggtcggt tccactgcct ccagagccca tcttatcaat 780
gatactattg accatgttgg tcacgccgtc gatagctttc tgagtagact ccttatcagc 840
ggcgtagcca gatccctgtt cgttggaatg gtggtagccg taccacccat ccaccattcc 900
ctgccacccg ccctcaataa accctgcgat agcgccgaac agtccgcgtt tctttctccg 960
gctttccctc tgtggtgaat ttctcagtcc ggttgccagg accagtcccc atccaatgtc 1020
ctgagcgtgt gtgacggtca cgttcttctc catgatagta tccacctgtt ctgtggagtt 1080
gttagcatga tacccaatac agatctggtc ggacttcacc agggacacga tagccagcag 1140
cagcacgatt ttttccat 1158
<210> 118
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 118
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 119
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 119
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 120
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 120
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaaa tccagagtcc gctcgttcag 720
cagcagcacc agcagctcag ccaggtctgt tccggagcct ccgctgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 121
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 121
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccattct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgatgc tgaaccagtt cactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 122
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 122
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Ile Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Met Leu
130 135 140
Asn Gln Phe Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 123
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 123
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaac agcagagtga actggttcag 720
catcagcacc agcagctcag ccaggtctgt tccggagcct ccgctgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca gaatggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 124
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 124
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcaatgga acaggcggag ctgacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 125
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 125
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Asn Gly Thr Gly Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 126
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 126
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaac agcagagtcc actggttcag 720
cagcagcacc agcagctcag ccaggtcagc tccgcctgtt ccattgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 127
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 127
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcggaaat ggcactggag ctgacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 128
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 128
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 129
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 129
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaac agcagagtcc actggttcag 720
cagcagcacc agcagctcag ccaggtcagc tccagtgcca tttccgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 130
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 130
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggcaacggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 131
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 131
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Asn Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 132
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 132
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaac agcagagtcc actggttcag 720
cagcagcacc agcagctcag ccaggtctgt tccgttgcct ccgctgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 133
<211> 33
<212> PRT
<213> A流感病毒
<400> 133
Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn Lys Leu Glu Arg
1 5 10 15
Arg Met Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe Leu Asp Ile
20 25 30
Trp
<210> 134
<211> 12
<212> PRT
<213> A流感病毒
<400> 134
Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn
1 5 10
<210> 135
<211> 12
<212> PRT
<213> A流感病毒
<400> 135
Asn Lys Leu Glu Arg Arg Met Glu Asn Leu Asn Lys
1 5 10
<210> 136
<211> 11
<212> PRT
<213> A流感病毒
<400> 136
Lys Lys Val Asp Asp Gly Phe Leu Asp Ile Trp
1 5 10
<210> 137
<211> 33
<212> PRT
<213> A流感病毒
<400> 137
Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn His Leu Glu Lys
1 5 10 15
Arg Ile Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe Leu Asp Ile
20 25 30
Trp
<210> 138
<211> 11
<212> PRT
<213> A流感病毒
<400> 138
Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe
1 5 10
<210> 139
<211> 11
<212> PRT
<213> A流感病毒
<400> 139
Phe Asn His Leu Glu Lys Arg Ile Glu Asn Leu
1 5 10
<210> 140
<211> 13
<212> PRT
<213> A流感病毒
<400> 140
Leu Asn Lys Lys Val Asp Asp Gly Phe Leu Asp Ile Trp
1 5 10
<210> 141
<211> 33
<212> PRT
<213> A流感病毒
<400> 141
Asn Thr Gln Phe Glu Ala Val Gly Lys Glu Phe Ser Asn Leu Glu Arg
1 5 10 15
Arg Leu Glu Asn Leu Asn Lys Lys Met Glu Asp Gly Phe Leu Asp Val
20 25 30
Trp
<210> 142
<211> 11
<212> PRT
<213> A流感病毒
<400> 142
Asn Thr Gln Phe Glu Ala Val Gly Lys Glu Phe
1 5 10
<210> 143
<211> 12
<212> PRT
<213> A流感病毒
<400> 143
Phe Ser Asn Leu Glu Arg Arg Leu Glu Asn Leu Asn
1 5 10
<210> 144
<211> 12
<212> PRT
<213> A流感病毒
<400> 144
Asn Lys Lys Met Glu Asp Gly Phe Leu Asp Val Trp
1 5 10
<210> 145
<211> 33
<212> PRT
<213> A流感病毒
<400> 145
Asn Thr Gln Phe Glu Ala Val Gly Arg Glu Phe Asn Asn Leu Glu Arg
1 5 10 15
Arg Ile Glu Asn Leu Asn Lys Lys Met Glu Asp Gly Phe Leu Asp Val
20 25 30
Trp
<210> 146
<211> 11
<212> PRT
<213> A流感病毒
<400> 146
Asn Thr Gln Phe Glu Ala Val Gly Arg Glu Phe
1 5 10
<210> 147
<211> 12
<212> PRT
<213> A流感病毒
<400> 147
Phe Asn Asn Leu Glu Arg Arg Ile Glu Asn Leu Asn
1 5 10
<210> 148
<211> 12
<212> PRT
<213> A流感病毒
<400> 148
Asn Lys Lys Met Glu Asp Gly Phe Leu Asp Val Trp
1 5 10
<210> 149
<211> 53
<212> PRT
<213> A流感病毒
<400> 149
Lys Val Asn Ser Val Ile Glu Lys Met Asn Thr Gln Phe Thr Ala Val
1 5 10 15
Gly Lys Glu Phe Asn Lys Leu Glu Arg Arg Met Glu Asn Leu Asn Lys
20 25 30
Lys Val Asp Asp Gly Phe Leu Asp Ile Trp Thr Tyr Asn Ala Glu Leu
35 40 45
Leu Val Leu Leu Glu
50
<210> 150
<211> 20
<212> PRT
<213> A流感病毒
<400> 150
Lys Val Asn Ser Val Ile Glu Lys Met Thr Tyr Asn Ala Glu Leu Leu
1 5 10 15
Val Leu Leu Glu
20
<210> 151
<211> 53
<212> PRT
<213> A流感病毒
<400> 151
Lys Val Asn Ser Val Ile Glu Lys Met Asn Thr Gln Phe Thr Ala Val
1 5 10 15
Gly Lys Glu Phe Asn His Leu Glu Lys Arg Ile Glu Asn Leu Asn Lys
20 25 30
Lys Val Asp Asp Gly Phe Leu Asp Ile Trp Thr Tyr Asn Ala Glu Leu
35 40 45
Leu Val Leu Leu Glu
50
<210> 152
<211> 20
<212> PRT
<213> A流感病毒
<400> 152
Lys Val Asn Ser Val Ile Glu Lys Met Thr Tyr Asn Ala Glu Leu Leu
1 5 10 15
Val Leu Leu Glu
20
<210> 153
<211> 53
<212> PRT
<213> A流感病毒
<400> 153
Lys Val Asn Ser Val Ile Glu Lys Met Asn Thr Gln Phe Glu Ala Val
1 5 10 15
Gly Lys Glu Phe Ser Asn Leu Glu Arg Arg Leu Glu Asn Leu Asn Lys
20 25 30
Lys Met Glu Asp Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala Glu Leu
35 40 45
Leu Val Leu Met Glu
50
<210> 154
<211> 20
<212> PRT
<213> A流感病毒
<400> 154
Lys Val Asn Ser Val Ile Glu Lys Met Thr Tyr Asn Ala Glu Leu Leu
1 5 10 15
Val Leu Met Glu
20
<210> 155
<211> 53
<212> PRT
<213> A流感病毒
<400> 155
Lys Val Asn Ser Ile Ile Asp Lys Met Asn Thr Gln Phe Glu Ala Val
1 5 10 15
Gly Arg Glu Phe Asn Asn Leu Glu Arg Arg Ile Glu Asn Leu Asn Lys
20 25 30
Lys Met Glu Asp Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala Glu Leu
35 40 45
Leu Val Leu Met Glu
50
<210> 156
<211> 20
<212> PRT
<213> A流感病毒
<400> 156
Lys Val Asn Ser Ile Ile Asp Lys Met Thr Tyr Asn Ala Glu Leu Leu
1 5 10 15
Val Leu Met Glu
20
<210> 157
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 157
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctga tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 158
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 158
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Met
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 159
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 159
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcatcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 160
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 160
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctga tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 161
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 161
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Met
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 162
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 162
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaaa tccagagtcc gctcgttcat 720
cagcagcacc agcagctcag ccaggtctgt tccggagcct ccgctgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 163
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 163
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatcgtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctga tcaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 164
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 164
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Ile Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 165
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 165
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttgatcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacga tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 166
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 166
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatcgtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctga tcaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 167
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 167
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Ile Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 168
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 168
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaaa tccagagtcc gctcgttgat 720
cagcagcacc agcagctcag ccaggtctgt tccggagcct ccgctgccca ttttttcgat 780
gacagaattc acgatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 169
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 169
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacctggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctga tcaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 170
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 170
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 171
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 171
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttgatcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca ggttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 172
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 172
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacctggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctga tcaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 173
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 173
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 174
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 174
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaaa tccagagtcc gctcgttgat 720
cagcagcacc agcagctcag ccaggtctgt tccggagcct ccgctgccca ttttttcgat 780
gacagaattc accaggttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 175
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 175
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacctggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 176
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 176
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 177
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 177
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca ggttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 178
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 178
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacctggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 179
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 179
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 180
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 180
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaaa tccagagtcc gctcgttcag 720
cagcagcacc agcagctcag ccaggtctgt tccggagcct ccgctgccca ttttttcgat 780
gacagaattc accaggttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 181
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 181
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc ataacaatac ccagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcggaaat ggcactggag ctgacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 182
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 182
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 183
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 183
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtcagctcca gtgccatttc cgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgggtatt 360
gttatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 184
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 184
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc ataacaatac ccagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcggaaat ggcactggag ctgacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgaaca gcaccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 185
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 185
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Asn Ser Thr Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 186
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 186
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggtgct gttcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaac agcagagtcc actggttcag 720
cagcagcacc agcagctcag ccaggtcagc tccagtgcca tttccgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctggg tattgttatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 187
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 187
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc ataacaatac ccagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcggaaat ggcactggag ctgacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 188
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 188
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 189
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 189
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtcagctcca gtgccatttc cgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgggtatt 360
gttatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 190
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 190
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc ataacaatac ccagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcggaaat ggcactggag ctgacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgaaca gcaccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtcaacc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 191
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 191
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Asn Ser Thr Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Asn Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 192
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 192
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
gttgacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggtgct gttcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaac agcagagtcc actggttcag 720
cagcagcacc agcagctcag ccaggtcagc tccagtgcca tttccgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctggg tattgttatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 193
<211> 465
<212> DNA
<213> Aquifex aeolicus
<400> 193
atgcaaattt acgaagggaa actaaccgct gaagggctga ggttcggtat agtggcttcc 60
aggttcaacc acgcactcgt ggatagacta gttgagggag ctatagactg catagtaaga 120
cacgggggaa gggaagaaga cataacgctc gttagagtgc cgggctcctg ggaaattccc 180
gtggctgcgg gagagcttgc gagaaaagag gacatagacg ctgtgatagc gataggagtt 240
ctaataaggg gggctactcc ccactttgat tacatagcct ctgaagtgtc aaaagggctt 300
gcgaaccttt ccttagaact gagaaaaccc ataaccttcg gtgttataac tgcggacacc 360
ttggagcagg cgatagaaag ggcgggaaca aagcacggga ataagggctg ggaagctgca 420
ctttccgcaa tagaaatggc aaacttattt aagagtctga gatga 465
<210> 194
<211> 154
<212> PRT
<213> Aquifex aeolicus
<400> 194
Met Gln Ile Tyr Glu Gly Lys Leu Thr Ala Glu Gly Leu Arg Phe Gly
1 5 10 15
Ile Val Ala Ser Arg Phe Asn His Ala Leu Val Asp Arg Leu Val Glu
20 25 30
Gly Ala Ile Asp Cys Ile Val Arg His Gly Gly Arg Glu Glu Asp Ile
35 40 45
Thr Leu Val Arg Val Pro Gly Ser Trp Glu Ile Pro Val Ala Ala Gly
50 55 60
Glu Leu Ala Arg Lys Glu Asp Ile Asp Ala Val Ile Ala Ile Gly Val
65 70 75 80
Leu Ile Arg Gly Ala Thr Pro His Phe Asp Tyr Ile Ala Ser Glu Val
85 90 95
Ser Lys Gly Leu Ala Asn Leu Ser Leu Glu Leu Arg Lys Pro Ile Thr
100 105 110
Phe Gly Val Ile Thr Ala Asp Thr Leu Glu Gln Ala Ile Glu Arg Ala
115 120 125
Gly Thr Lys His Gly Asn Lys Gly Trp Glu Ala Ala Leu Ser Ala Ile
130 135 140
Glu Met Ala Asn Leu Phe Lys Ser Leu Arg
145 150
<210> 195
<211> 465
<212> DNA
<213> Aquifex aeolicus
<400> 195
tcatctcaga ctcttaaata agtttgccat ttctattgcg gaaagtgcag cttcccagcc 60
cttattcccg tgctttgttc ccgccctttc tatcgcctgc tccaaggtgt ccgcagttat 120
aacaccgaag gttatgggtt ttctcagttc taaggaaagg ttcgcaagcc cttttgacac 180
ttcagaggct atgtaatcaa agtggggagt agcccccctt attagaactc ctatcgctat 240
cacagcgtct atgtcctctt ttctcgcaag ctctcccgca gccacgggaa tttcccagga 300
gcccggcact ctaacgagcg ttatgtcttc ttcccttccc ccgtgtctta ctatgcagtc 360
tatagctccc tcaactagtc tatccacgag tgcgtggttg aacctggaag ccactatacc 420
gaacctcagc ccttcagcgg ttagtttccc ttcgtaaatt tgcat 465
<210> 196
<211> 642
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 196
atgaaggcca agctgctggt gctcctgtgc accttcaccg ccacctacgc cgacaccatc 60
tgcatcggct accacgccaa caacagcacc gacaccgtgg ataccgtgct ggaaaagaac 120
gtgaccgtga cccacagcgt gaacctgggc agcggcctgc ggatggtgac aggcctgcgg 180
aacatccccc agagagagac acggggcctg ttcggcgcca ttgccggctt tatcgagggc 240
ggctggaccg gcatggtgga cgggtggtac ggctaccacc accagaacga gcagggcagc 300
ggctacgccg ccgaccagaa gtccacccag aacgccatca acggcatcac caacatggtg 360
aacagcgtga tcgagaagat gggctccggc ggcagcggca ccgatctggc tgaactgctg 420
gtcctgctgc tgaacgagcg gaccctggac ttccacgaca gcaacgtgaa gaacctgtac 480
gagaaagtga agtcccagct gaagaacaac gccaaagaga tcggcaacgg ctgcttcgag 540
ttctaccaca agtgcaacaa cgagtgcatg gaaagcgtga agaacggcac ctacgactac 600
cccaagtaca gcgaggaaag caagctgaac cgcgagggag gc 642
<210> 197
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 197
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Gly Gly
210
<210> 198
<211> 642
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 198
gcctccctcg cggttcagct tgctttcctc gctgtacttg gggtagtcgt aggtgccgtt 60
cttcacgctt tccatgcact cgttgttgca cttgtggtag aactcgaagc agccgttgcc 120
gatctctttg gcgttgttct tcagctggga cttcactttc tcgtacaggt tcttcacgtt 180
gctgtcgtgg aagtccaggg tccgctcgtt cagcagcagg accagcagtt cagccagatc 240
ggtgccgctg ccgccggagc ccatcttctc gatcacgctg ttcaccatgt tggtgatgcc 300
gttgatggcg ttctgggtgg acttctggtc ggcggcgtag ccgctgccct gctcgttctg 360
gtggtggtag ccgtaccacc cgtccaccat gccggtccag ccgccctcga taaagccggc 420
aatggcgccg aacaggcccc gtgtctctct ctgggggatg ttccgcaggc ctgtcaccat 480
ccgcaggccg ctgcccaggt tcacgctgtg ggtcacggtc acgttctttt ccagcacggt 540
atccacggtg tcggtgctgt tgttggcgtg gtagccgatg cagatggtgt cggcgtaggt 600
ggcggtgaag gtgcacagga gcaccagcag cttggccttc at 642
<210> 199
<211> 1104
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 199
atgaaggcca agctgctggt gctcctgtgc accttcaccg ccacctacgc cgacaccatc 60
tgcatcggct accacgccaa caacagcacc gacaccgtgg ataccgtgct ggaaaagaac 120
gtgaccgtga cccacagcgt gaacctgggc agcggcctgc ggatggtgac aggcctgcgg 180
aacatccccc agagagagac acggggcctg ttcggcgcca ttgccggctt tatcgagggc 240
ggctggaccg gcatggtgga cgggtggtac ggctaccacc accagaacga gcagggcagc 300
ggctacgccg ccgaccagaa gtccacccag aacgccatca acggcatcac caacatggtg 360
aacagcgtga tcgagaagat gggctccggc ggcagcggca ccgatctggc tgaactgctg 420
gtcctgctgc tgaacgagcg gaccctggac ttccacgaca gcaacgtgaa gaacctgtac 480
gagaaagtga agtcccagct gaagaacaac gccaaagaga tcggcaacgg ctgcttcgag 540
ttctaccaca agtgcaacaa cgagtgcatg gaaagcgtga agaacggcac ctacgactac 600
cccaagtaca gcgaggaaag caagctgaac cgcgagggag gcatgcaaat ctacgagggc 660
aagctgacag ccgagggcct gagattcggc atcgtggcca gccggttcaa ccacgccctg 720
gtggacagac tggtggaagg cgccatcgac tgcatcgtgc ggcacggcgg cagagaagag 780
gacatcaccc tggtccgcgt gcccggcagc tgggaaattc ctgtggctgc cggcgagctg 840
gcccggaaag aggatatcga cgccgtcatc gccatcggcg tgctgatcag aggcgccacc 900
ccccacttcg actatatcgc cagcgaggtg tccaagggcc tggccaacct gagcctggaa 960
ctgcggaagc ccatcacctt cggagtgatc accgccgaca ccctggaaca ggccatcgag 1020
agagccggca ccaagcacgg caacaaggga tgggaagccg ccctgagcgc catcgagatg 1080
gccaatctgt tcaagagcct gcgc 1104
<210> 200
<211> 368
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 200
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Gly Gly Met Gln Ile Tyr Glu Gly Lys Leu Thr Ala
210 215 220
Glu Gly Leu Arg Phe Gly Ile Val Ala Ser Arg Phe Asn His Ala Leu
225 230 235 240
Val Asp Arg Leu Val Glu Gly Ala Ile Asp Cys Ile Val Arg His Gly
245 250 255
Gly Arg Glu Glu Asp Ile Thr Leu Val Arg Val Pro Gly Ser Trp Glu
260 265 270
Ile Pro Val Ala Ala Gly Glu Leu Ala Arg Lys Glu Asp Ile Asp Ala
275 280 285
Val Ile Ala Ile Gly Val Leu Ile Arg Gly Ala Thr Pro His Phe Asp
290 295 300
Tyr Ile Ala Ser Glu Val Ser Lys Gly Leu Ala Asn Leu Ser Leu Glu
305 310 315 320
Leu Arg Lys Pro Ile Thr Phe Gly Val Ile Thr Ala Asp Thr Leu Glu
325 330 335
Gln Ala Ile Glu Arg Ala Gly Thr Lys His Gly Asn Lys Gly Trp Glu
340 345 350
Ala Ala Leu Ser Ala Ile Glu Met Ala Asn Leu Phe Lys Ser Leu Arg
355 360 365
<210> 201
<211> 1104
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 201
gcgcaggctc ttgaacagat tggccatctc gatggcgctc agggcggctt cccatccctt 60
gttgccgtgc ttggtgccgg ctctctcgat ggcctgttcc agggtgtcgg cggtgatcac 120
tccgaaggtg atgggcttcc gcagttccag gctcaggttg gccaggccct tggacacctc 180
gctggcgata tagtcgaagt ggggggtggc gcctctgatc agcacgccga tggcgatgac 240
ggcgtcgata tcctctttcc gggccagctc gccggcagcc acaggaattt cccagctgcc 300
gggcacgcgg accagggtga tgtcctcttc tctgccgccg tgccgcacga tgcagtcgat 360
ggcgccttcc accagtctgt ccaccagggc gtggttgaac cggctggcca cgatgccgaa 420
tctcaggccc tcggctgtca gcttgccctc gtagatttgc atgcctccct cgcggttcag 480
cttgctttcc tcgctgtact tggggtagtc gtaggtgccg ttcttcacgc tttccatgca 540
ctcgttgttg cacttgtggt agaactcgaa gcagccgttg ccgatctctt tggcgttgtt 600
cttcagctgg gacttcactt tctcgtacag gttcttcacg ttgctgtcgt ggaagtccag 660
ggtccgctcg ttcagcagca ggaccagcag ttcagccaga tcggtgccgc tgccgccgga 720
gcccatcttc tcgatcacgc tgttcaccat gttggtgatg ccgttgatgg cgttctgggt 780
ggacttctgg tcggcggcgt agccgctgcc ctgctcgttc tggtggtggt agccgtacca 840
cccgtccacc atgccggtcc agccgccctc gataaagccg gcaatggcgc cgaacaggcc 900
ccgtgtctct ctctggggga tgttccgcag gcctgtcacc atccgcaggc cgctgcccag 960
gttcacgctg tgggtcacgg tcacgttctt ttccagcacg gtatccacgg tgtcggtgct 1020
gttgttggcg tggtagccga tgcagatggt gtcggcgtag gtggcggtga aggtgcacag 1080
gagcaccagc agcttggcct tcat 1104
<210> 202
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 202
atgaaggcca agctgctggt gctcctgtgc accttcaccg ccacctacgc cgacaccatc 60
tgcatcggct accacgccaa caacagcacc gacaccgtgg ataccgtgct ggaaaagaac 120
gtgaccgtga cccacagcgt gaacctgggc agcggcctgc ggatggtgac aggcctgcgg 180
aacatccccc agagagagac acggggcctg ttcggcgcca ttgccggctt tatcgagggc 240
ggctggaccg gcatggtgga cgggtggtac ggctaccacc accagaacga gcagggcagc 300
ggctacgccg ccgaccagaa gtccacccag aacgccatca acggcatcac caacatggtg 360
aacagcgtga tcgagaagat gggctccggc ggcagcggca ccgatctggc tgaactgctg 420
gtcctgctgc tgaacgagcg gaccctggac ttccacgaca gcaacgtgaa gaacctgtac 480
gagaaagtga agtcccagct gaagaacaac gccaaagaga tcggcaacgg ctgcttcgag 540
ttctaccaca agtgcaacaa cgagtgcatg gaaagcgtga agaacggcac ctacgactac 600
cccaagtaca gcgaggaaag caagctgaac cgcgagggaa gcggc 645
<210> 203
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 203
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Gly Ser Gly
210 215
<210> 204
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 204
gccgcttccc tcgcggttca gcttgctttc ctcgctgtac ttggggtagt cgtaggtgcc 60
gttcttcacg ctttccatgc actcgttgtt gcacttgtgg tagaactcga agcagccgtt 120
gccgatctct ttggcgttgt tcttcagctg ggacttcact ttctcgtaca ggttcttcac 180
gttgctgtcg tggaagtcca gggtccgctc gttcagcagc aggaccagca gttcagccag 240
atcggtgccg ctgccgccgg agcccatctt ctcgatcacg ctgttcacca tgttggtgat 300
gccgttgatg gcgttctggg tggacttctg gtcggcggcg tagccgctgc cctgctcgtt 360
ctggtggtgg tagccgtacc acccgtccac catgccggtc cagccgccct cgataaagcc 420
ggcaatggcg ccgaacaggc cccgtgtctc tctctggggg atgttccgca ggcctgtcac 480
catccgcagg ccgctgccca ggttcacgct gtgggtcacg gtcacgttct tttccagcac 540
ggtatccacg gtgtcggtgc tgttgttggc gtggtagccg atgcagatgg tgtcggcgta 600
ggtggcggtg aaggtgcaca ggagcaccag cagcttggcc ttcat 645
<210> 205
<211> 1107
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 205
atgaaggcca agctgctggt gctcctgtgc accttcaccg ccacctacgc cgacaccatc 60
tgcatcggct accacgccaa caacagcacc gacaccgtgg ataccgtgct ggaaaagaac 120
gtgaccgtga cccacagcgt gaacctgggc agcggcctgc ggatggtgac aggcctgcgg 180
aacatccccc agagagagac acggggcctg ttcggcgcca ttgccggctt tatcgagggc 240
ggctggaccg gcatggtgga cgggtggtac ggctaccacc accagaacga gcagggcagc 300
ggctacgccg ccgaccagaa gtccacccag aacgccatca acggcatcac caacatggtg 360
aacagcgtga tcgagaagat gggctccggc ggcagcggca ccgatctggc tgaactgctg 420
gtcctgctgc tgaacgagcg gaccctggac ttccacgaca gcaacgtgaa gaacctgtac 480
gagaaagtga agtcccagct gaagaacaac gccaaagaga tcggcaacgg ctgcttcgag 540
ttctaccaca agtgcaacaa cgagtgcatg gaaagcgtga agaacggcac ctacgactac 600
cccaagtaca gcgaggaaag caagctgaac cgcgagggaa gcggcatgca aatctacgag 660
ggcaagctga cagccgaggg cctgagattc ggcatcgtgg ccagccggtt caaccacgcc 720
ctggtggaca gactggtgga aggcgccatc gactgcatcg tgcggcacgg cggcagagaa 780
gaggacatca ccctggtccg cgtgcccggc agctgggaaa ttcctgtggc tgccggcgag 840
ctggcccgga aagaggatat cgacgccgtc atcgccatcg gcgtgctgat cagaggcgcc 900
accccccact tcgactatat cgccagcgag gtgtccaagg gcctggccaa cctgagcctg 960
gaactgcgga agcccatcac cttcggagtg atcaccgccg acaccctgga acaggccatc 1020
gagagagccg gcaccaagca cggcaacaag ggatgggaag ccgccctgag cgccatcgag 1080
atggccaatc tgttcaagag cctgcgc 1107
<210> 206
<211> 369
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 206
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Gly Ser Gly Met Gln Ile Tyr Glu Gly Lys Leu Thr
210 215 220
Ala Glu Gly Leu Arg Phe Gly Ile Val Ala Ser Arg Phe Asn His Ala
225 230 235 240
Leu Val Asp Arg Leu Val Glu Gly Ala Ile Asp Cys Ile Val Arg His
245 250 255
Gly Gly Arg Glu Glu Asp Ile Thr Leu Val Arg Val Pro Gly Ser Trp
260 265 270
Glu Ile Pro Val Ala Ala Gly Glu Leu Ala Arg Lys Glu Asp Ile Asp
275 280 285
Ala Val Ile Ala Ile Gly Val Leu Ile Arg Gly Ala Thr Pro His Phe
290 295 300
Asp Tyr Ile Ala Ser Glu Val Ser Lys Gly Leu Ala Asn Leu Ser Leu
305 310 315 320
Glu Leu Arg Lys Pro Ile Thr Phe Gly Val Ile Thr Ala Asp Thr Leu
325 330 335
Glu Gln Ala Ile Glu Arg Ala Gly Thr Lys His Gly Asn Lys Gly Trp
340 345 350
Glu Ala Ala Leu Ser Ala Ile Glu Met Ala Asn Leu Phe Lys Ser Leu
355 360 365
Arg
<210> 207
<211> 1107
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 207
gcgcaggctc ttgaacagat tggccatctc gatggcgctc agggcggctt cccatccctt 60
gttgccgtgc ttggtgccgg ctctctcgat ggcctgttcc agggtgtcgg cggtgatcac 120
tccgaaggtg atgggcttcc gcagttccag gctcaggttg gccaggccct tggacacctc 180
gctggcgata tagtcgaagt ggggggtggc gcctctgatc agcacgccga tggcgatgac 240
ggcgtcgata tcctctttcc gggccagctc gccggcagcc acaggaattt cccagctgcc 300
gggcacgcgg accagggtga tgtcctcttc tctgccgccg tgccgcacga tgcagtcgat 360
ggcgccttcc accagtctgt ccaccagggc gtggttgaac cggctggcca cgatgccgaa 420
tctcaggccc tcggctgtca gcttgccctc gtagatttgc atgccgcttc cctcgcggtt 480
cagcttgctt tcctcgctgt acttggggta gtcgtaggtg ccgttcttca cgctttccat 540
gcactcgttg ttgcacttgt ggtagaactc gaagcagccg ttgccgatct ctttggcgtt 600
gttcttcagc tgggacttca ctttctcgta caggttcttc acgttgctgt cgtggaagtc 660
cagggtccgc tcgttcagca gcaggaccag cagttcagcc agatcggtgc cgctgccgcc 720
ggagcccatc ttctcgatca cgctgttcac catgttggtg atgccgttga tggcgttctg 780
ggtggacttc tggtcggcgg cgtagccgct gccctgctcg ttctggtggt ggtagccgta 840
ccacccgtcc accatgccgg tccagccgcc ctcgataaag ccggcaatgg cgccgaacag 900
gccccgtgtc tctctctggg ggatgttccg caggcctgtc accatccgca ggccgctgcc 960
caggttcacg ctgtgggtca cggtcacgtt cttttccagc acggtatcca cggtgtcggt 1020
gctgttgttg gcgtggtagc cgatgcagat ggtgtcggcg taggtggcgg tgaaggtgca 1080
caggagcacc agcagcttgg ccttcat 1107
<210> 208
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 208
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccaa gcatccagag cagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 209
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 209
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 210
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 210
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctctgctctg gatgcttggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 211
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 211
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccaa gcatccagag cagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaaccagtg gactctgctg ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 212
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 212
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 213
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 213
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaac agcagagtcc actggttcag 720
cagcagcacc agcagctcag ccaggtctgt tccggagcct ccgctgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctctgc tctggatgct 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattca ctgagtgggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 214
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 214
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asp Glu Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Tyr His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 215
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 215
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asp Glu Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Tyr His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 216
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 216
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa catacaacgc tgagctgctg 420
gtgctgctgc tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 217
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 217
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 218
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 218
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcagcagc agcaccagca gctcagcgtt 240
gtatgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 219
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 219
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca cccactcagt gaatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa catacaacgc tgagctgctg 420
gtgctgctgc tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 220
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 220
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 221
<211> 1151
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 221
rctgacccac tttttctgga cttggcaatg cccttcacat actgatctgc caggtacagg 60
ccatgattct cgtttccaat cagttcgatt ttatccagga tgtccttaaa caggacctcc 120
tcctcgtgct gctcggccac gtaccactgc agaaagttga aggtagcatg atctttgctc 180
ttaatggcgt ggtccacaat attgttgata gattcggaaa tatgctgctc gtgttcgtaa 240
gctttctgaa agatctgggt caggccctcg aacttatgtt caggggcgct gattgaagtc 300
agctggacgg gcacattgtt ctcattcagg aaaatgatca gtttctttgc atgttcgtat 360
tcctcggctg cgtgatcaaa caggaacagc ccagcgccgt ccagtgagtg tgtataacac 420
caactagaca tactcatgta caggttggag ctctgcatct ccttgttcac ctgttcgttc 480
agcagcttga tgatgtcgcc cccactgtca attttctctc gattcagctt actctcttca 540
gaatatttgg gatagtcgta agtgccgttc ttcacagact ccatacattc attgttgcac 600
ttatggtaaa actcgaagca tccattcccg atttctttgg cattgttctt cagctgggat 660
ttgaccttct catacagatt cttcacgttg ctatcgtgga aatccagagt ccgctcgttc 720
agcagcagca ccagcagctc agcgttgtat gttccggagc ctccgctgcc cattttttcg 780
atgacagaat tcaccatgtt agtaatgcca ttgattgcgt tctgtgtaga cttctgatca 840
gcggcgtagc cgctgccctg ctcattctga tggtggtagc cgtaccaccc gtccaccatt 900
cctgtccacc cgccctcaat aaaccctgcg atagcgccga acagtcctct tgtttcccgc 960
tgtgggatgt tgcgcagtcc ggtgaccatc ctcagtccgc tgcccagatt cactgagtgg 1020
gtgacagtca cgttcttctc caggacggta tccactgtgt cggtggagtt gtttgcgtga 1080
tagccgatgc agatagtgtc agcgtaggtt gcggtaaaag tacacagcag gaccagcagt 1140
ttggccttca t 1151
<210> 222
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 222
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 223
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 223
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 224
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 224
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Ile Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 225
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 225
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Ile Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 226
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 226
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 227
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 227
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 228
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 228
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 229
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 229
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 230
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 230
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Met
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 231
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 231
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Met
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 232
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 232
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Gln Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Gln
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 233
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 233
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Gln Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Gln
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 234
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 234
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca ccaactcaac taatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgac 645
<210> 235
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 235
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr Asn Ser Thr Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 236
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 236
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattagttga gttggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 237
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 237
atgaaggcca aactgctggt cctgctgtgt acttttaccg caacctacgc tgacactatc 60
tgcatcggct atcacgcaaa caactccacc gacacagtgg ataccgtcct ggagaagaac 120
gtgactgtca ccaactcaac taatctgggc agcggactga ggatggtcac cggactgcgc 180
aacatcccac agcgggaaac aagaggactg ttcggcgcta tcgcagggtt tattgagggc 240
gggtggacag gaatggtgga cgggtggtac ggctaccacc atcagaatga gcagggcagc 300
ggctacgccg ctgatcagaa gtctacacag aacgcaatca atggcattac taacatggtg 360
aattctgtca tcgaaaaaat gggcagcgga ggctccggaa cagacctggc tgagctgctg 420
gtgctgctgc tgaacgagcg gactctggat ttccacgata gcaacgtgaa gaatctgtat 480
gagaaggtca aatcccagct gaagaacaat gccaaagaaa tcgggaatgg atgcttcgag 540
ttttaccata agtgcaacaa tgaatgtatg gagtctgtga agaacggcac ttacgactat 600
cccaaatatt ctgaagagag taagctgaat cgagagaaaa ttgacagtgg gggcgacatc 660
atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga gctccaacct gtacatgagt 720
atgtctagtt ggtgttatac acactcactg gacggcgctg ggctgttcct gtttgatcac 780
gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt tcctgaatga gaacaatgtg 840
cccgtccagc tgacttcaat cagcgcccct gaacataagt tcgagggcct gacccagatc 900
tttcagaaag cttacgaaca cgagcagcat atttccgaat ctatcaacaa tattgtggac 960
cacgccatta agagcaaaga tcatgctacc ttcaactttc tgcagtggta cgtggccgag 1020
cagcacgagg aggaggtcct gtttaaggac atcctggata aaatcgaact gattggaaac 1080
gagaatcatg gcctgtacct ggcagatcag tatgtgaagg gcattgccaa gtccagaaaa 1140
agtgggtca 1149
<210> 238
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 238
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr Asn Ser Thr Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 239
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 239
tgacccactt tttctggact tggcaatgcc cttcacatac tgatctgcca ggtacaggcc 60
atgattctcg tttccaatca gttcgatttt atccaggatg tccttaaaca ggacctcctc 120
ctcgtgctgc tcggccacgt accactgcag aaagttgaag gtagcatgat ctttgctctt 180
aatggcgtgg tccacaatat tgttgataga ttcggaaata tgctgctcgt gttcgtaagc 240
tttctgaaag atctgggtca ggccctcgaa cttatgttca ggggcgctga ttgaagtcag 300
ctggacgggc acattgttct cattcaggaa aatgatcagt ttctttgcat gttcgtattc 360
ctcggctgcg tgatcaaaca ggaacagccc agcgccgtcc agtgagtgtg tataacacca 420
actagacata ctcatgtaca ggttggagct ctgcatctcc ttgttcacct gttcgttcag 480
cagcttgatg atgtcgcccc cactgtcaat tttctctcga ttcagcttac tctcttcaga 540
atatttggga tagtcgtaag tgccgttctt cacagactcc atacattcat tgttgcactt 600
atggtaaaac tcgaagcatc cattcccgat ttctttggca ttgttcttca gctgggattt 660
gaccttctca tacagattct tcacgttgct atcgtggaaa tccagagtcc gctcgttcag 720
cagcagcacc agcagctcag ccaggtctgt tccggagcct ccgctgccca ttttttcgat 780
gacagaattc accatgttag taatgccatt gattgcgttc tgtgtagact tctgatcagc 840
ggcgtagccg ctgccctgct cattctgatg gtggtagccg taccacccgt ccaccattcc 900
tgtccacccg ccctcaataa accctgcgat agcgccgaac agtcctcttg tttcccgctg 960
tgggatgttg cgcagtccgg tgaccatcct cagtccgctg cccagattag ttgagttggt 1020
gacagtcacg ttcttctcca ggacggtatc cactgtgtcg gtggagttgt ttgcgtgata 1080
gccgatgcag atagtgtcag cgtaggttgc ggtaaaagta cacagcagga ccagcagttt 1140
ggccttcat 1149
<210> 240
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 240
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Ile Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Met Leu
130 135 140
Asn Gln Phe Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 241
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 241
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Ile Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Met Leu
130 135 140
Asn Gln Phe Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 242
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 242
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Asn Gly Thr Gly Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 243
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 243
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Asn Gly Thr Gly Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 244
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 244
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 245
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 245
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 246
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 246
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Asn Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 247
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 247
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Asn Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 248
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 248
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 249
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 249
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Asn Ser Thr Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 250
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 250
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 251
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 251
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Asn Ser Thr Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Asn Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 252
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 252
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Gly Gly
210
<210> 253
<211> 368
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 253
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Gly Gly Met Gln Ile Tyr Glu Gly Lys Leu Thr Ala
210 215 220
Glu Gly Leu Arg Phe Gly Ile Val Ala Ser Arg Phe Asn His Ala Leu
225 230 235 240
Val Asp Arg Leu Val Glu Gly Ala Ile Asp Cys Ile Val Arg His Gly
245 250 255
Gly Arg Glu Glu Asp Ile Thr Leu Val Arg Val Pro Gly Ser Trp Glu
260 265 270
Ile Pro Val Ala Ala Gly Glu Leu Ala Arg Lys Glu Asp Ile Asp Ala
275 280 285
Val Ile Ala Ile Gly Val Leu Ile Arg Gly Ala Thr Pro His Phe Asp
290 295 300
Tyr Ile Ala Ser Glu Val Ser Lys Gly Leu Ala Asn Leu Ser Leu Glu
305 310 315 320
Leu Arg Lys Pro Ile Thr Phe Gly Val Ile Thr Ala Asp Thr Leu Glu
325 330 335
Gln Ala Ile Glu Arg Ala Gly Thr Lys His Gly Asn Lys Gly Trp Glu
340 345 350
Ala Ala Leu Ser Ala Ile Glu Met Ala Asn Leu Phe Lys Ser Leu Arg
355 360 365
<210> 254
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 254
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Gly Ser Gly
210 215
<210> 255
<211> 369
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 255
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Gly Ser Gly Met Gln Ile Tyr Glu Gly Lys Leu Thr
210 215 220
Ala Glu Gly Leu Arg Phe Gly Ile Val Ala Ser Arg Phe Asn His Ala
225 230 235 240
Leu Val Asp Arg Leu Val Glu Gly Ala Ile Asp Cys Ile Val Arg His
245 250 255
Gly Gly Arg Glu Glu Asp Ile Thr Leu Val Arg Val Pro Gly Ser Trp
260 265 270
Glu Ile Pro Val Ala Ala Gly Glu Leu Ala Arg Lys Glu Asp Ile Asp
275 280 285
Ala Val Ile Ala Ile Gly Val Leu Ile Arg Gly Ala Thr Pro His Phe
290 295 300
Asp Tyr Ile Ala Ser Glu Val Ser Lys Gly Leu Ala Asn Leu Ser Leu
305 310 315 320
Glu Leu Arg Lys Pro Ile Thr Phe Gly Val Ile Thr Ala Asp Thr Leu
325 330 335
Glu Gln Ala Ile Glu Arg Ala Gly Thr Lys His Gly Asn Lys Gly Trp
340 345 350
Glu Ala Ala Leu Ser Ala Ile Glu Met Ala Asn Leu Phe Lys Ser Leu
355 360 365
Arg
<210> 256
<211> 211
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 256
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Gly Gly
210
<210> 257
<211> 364
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 257
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Gly Gly Gln Ile Tyr Glu Gly Lys Leu Thr Ala Glu Gly Leu Arg
210 215 220
Phe Gly Ile Val Ala Ser Arg Phe Asn His Ala Leu Val Asp Arg Leu
225 230 235 240
Val Glu Gly Ala Ile Asp Cys Ile Val Arg His Gly Gly Arg Glu Glu
245 250 255
Asp Ile Thr Leu Val Arg Val Pro Gly Ser Trp Glu Ile Pro Val Ala
260 265 270
Ala Gly Glu Leu Ala Arg Lys Glu Asp Ile Asp Ala Val Ile Ala Ile
275 280 285
Gly Val Leu Ile Arg Gly Ala Thr Pro His Phe Asp Tyr Ile Ala Ser
290 295 300
Glu Val Ser Lys Gly Leu Ala Asn Leu Ser Leu Glu Leu Arg Lys Pro
305 310 315 320
Ile Thr Phe Gly Val Ile Thr Ala Asp Thr Leu Glu Gln Ala Ile Glu
325 330 335
Arg Ala Gly Thr Lys His Gly Asn Lys Gly Trp Glu Ala Ala Leu Ser
340 345 350
Ala Ile Glu Met Ala Asn Leu Phe Lys Ser Leu Arg
355 360
<210> 258
<211> 212
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 258
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Gly Ser Gly
210
<210> 259
<211> 365
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 259
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Ser
50 55 60
Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Gly Ser Gly Gln Ile Tyr Glu Gly Lys Leu Thr Ala Glu Gly Leu
210 215 220
Arg Phe Gly Ile Val Ala Ser Arg Phe Asn His Ala Leu Val Asp Arg
225 230 235 240
Leu Val Glu Gly Ala Ile Asp Cys Ile Val Arg His Gly Gly Arg Glu
245 250 255
Glu Asp Ile Thr Leu Val Arg Val Pro Gly Ser Trp Glu Ile Pro Val
260 265 270
Ala Ala Gly Glu Leu Ala Arg Lys Glu Asp Ile Asp Ala Val Ile Ala
275 280 285
Ile Gly Val Leu Ile Arg Gly Ala Thr Pro His Phe Asp Tyr Ile Ala
290 295 300
Ser Glu Val Ser Lys Gly Leu Ala Asn Leu Ser Leu Glu Leu Arg Lys
305 310 315 320
Pro Ile Thr Phe Gly Val Ile Thr Ala Asp Thr Leu Glu Gln Ala Ile
325 330 335
Glu Arg Ala Gly Thr Lys His Gly Asn Lys Gly Trp Glu Ala Ala Leu
340 345 350
Ser Ala Ile Glu Met Ala Asn Leu Phe Lys Ser Leu Arg
355 360 365
<210> 260
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 260
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 261
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 261
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 262
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 262
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 263
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 263
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 264
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 264
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 265
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 265
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaacagca gagtccactg 720
gttcagcagc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 266
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 266
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acagacctgg 1800
ctgagctgct ggtgctgctg ctgaaccagt ggactctgct gttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 267
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 267
atg aag gca atc ctg gtc gtc ctg ctg tat act ttc gct acc gct aac 48
Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Ala Thr Ala Asn
1 5 10 15
gct gac acc ctg tgc atc ggc tat cac gct aac aac tca acc gac aca 96
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat act gtc ctg gag aag aac gtg act gtc acc cac tct gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agt gga ctg agg ctg gca act gga ctg cga aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa acc aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aac 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag gga tca ggc tac gcc gct gac ctg aag agc aca cag aat gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala
100 105 110
atc gat gaa att act aac atg gtg aat tcc gtc atc gag aaa atg ggc 384
Ile Asp Glu Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga acc gac ctg gca gaa ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg aca ctg ctg tac cac gat agt aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Tyr His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aaa gtc cga tca cag ctg aag aac aat gct aaa gaa atc ggg aat 528
Glu Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc gac aac acc tgt atg gag agc 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser
180 185 190
gtg aaa aat ggc aca tac gat tat ccc aag tat tcc gag gaa gcc aaa 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys
195 200 205
ctg aac aga gag gaa att gac 645
Leu Asn Arg Glu Glu Ile Asp
210 215
<210> 268
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 268
Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Ala Thr Ala Asn
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asp Glu Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Tyr His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys
195 200 205
Leu Asn Arg Glu Glu Ile Asp
210 215
<210> 269
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 269
gtcaatttcc tctctgttca gtttggcttc ctcggaatac ttgggataat cgtatgtgcc 60
atttttcacg ctctccatac aggtgttgtc gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttagcattgt tcttcagctg tgatcggact ttctcataca gattcttcac 180
gttactatcg tggtacagca gtgtccactg gttcagcagc agcaccagca gttctgccag 240
gtcggttccg gagcctccgc tgcccatttt ctcgatgacg gaattcacca tgttagtaat 300
ttcatcgatt gcattctgtg tgctcttcag gtcagcggcg tagcctgatc cctgctcgtt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctctggtttc ccgctgtggg atgtttcgca gtccagttgc 480
cagcctcagt ccactgccca gattcacaga gtgggtgaca gtcacgttct tctccaggac 540
agtatccact gtgtcggttg agttgttagc gtgatagccg atgcacaggg tgtcagcgtt 600
agcggtagcg aaagtataca gcaggacgac caggattgcc ttcat 645
<210> 270
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 270
atg aag gca atc ctg gtc gtc ctg ctg tat act ttc gct acc gct aac 48
Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Ala Thr Ala Asn
1 5 10 15
gct gac acc ctg tgc atc ggc tat cac gct aac aac tca acc gac aca 96
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat act gtc ctg gag aag aac gtg act gtc acc cac tct gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agt gga ctg agg ctg gca act gga ctg cga aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa acc aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aac 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag gga tca ggc tac gcc gct gac ctg aag agc aca cag aat gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala
100 105 110
atc gat gaa att act aac atg gtg aat tcc gtc atc gag aaa atg ggc 384
Ile Asp Glu Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga acc gac ctg gca gaa ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg aca ctg ctg tac cac gat agt aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Tyr His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aaa gtc cga tca cag ctg aag aac aat gct aaa gaa atc ggg aat 528
Glu Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc gac aac acc tgt atg gag agc 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser
180 185 190
gtg aaa aat ggc aca tac gat tat ccc aag tat tcc gag gaa gcc aaa 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys
195 200 205
ctg aac aga gag gaa att gac tct ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Glu Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtc aac aag gag atg cag agc tcc aat ctg tac atg tcc 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat acc cac tct ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aac gag aac aat gtg ccc gtc cag ctg aca tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg act cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agt aaa gat cat gct acc ttc aat ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag agc cgg aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 271
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 271
Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Ala Thr Ala Asn
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Leu Ala Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asp Glu Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Tyr His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys
195 200 205
Leu Asn Arg Glu Glu Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 272
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 272
tcatcatgac ccacttttcc ggctcttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaaa ttgaaggtag catgatcttt 180
actcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gagtcaggcc ctcgaactta tgttcagggg cgctgattga 300
tgtcagctgg acgggcacat tgttctcgtt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagag agtgggtata 420
acaccaacta gacatggaca tgtacagatt ggagctctgc atctccttgt tgacctgttc 480
gttcagcagc ttgatgatgt cgcccccaga gtcaatttcc tctctgttca gtttggcttc 540
ctcggaatac ttgggataat cgtatgtgcc atttttcacg ctctccatac aggtgttgtc 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttagcattgt tcttcagctg 660
tgatcggact ttctcataca gattcttcac gttactatcg tggtacagca gtgtccactg 720
gttcagcagc agcaccagca gttctgccag gtcggttccg gagcctccgc tgcccatttt 780
ctcgatgacg gaattcacca tgttagtaat ttcatcgatt gcattctgtg tgctcttcag 840
gtcagcggcg tagcctgatc cctgctcgtt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctctggtttc 960
ccgctgtggg atgtttcgca gtccagttgc cagcctcagt ccactgccca gattcacaga 1020
gtgggtgaca gtcacgttct tctccaggac agtatccact gtgtcggttg agttgttagc 1080
gtgatagccg atgcacaggg tgtcagcgtt agcggtagcg aaagtataca gcaggacgac 1140
caggattgcc ttcat 1155
<210> 273
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 273
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggca atcctggtcg tcctgctgta tactttcgct accgctaacg 1440
ctgacaccct gtgcatcggc tatcacgcta acaactcaac cgacacagtg gatactgtcc 1500
tggagaagaa cgtgactgtc acccactctg tgaatctggg cagtggactg aggctggcaa 1560
ctggactgcg aaacatccca cagcgggaaa ccagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaacg 1680
agcagggatc aggctacgcc gctgacctga agagcacaca gaatgcaatc gatgaaatta 1740
ctaacatggt gaattccgtc atcgagaaaa tgggcagcgg aggctccgga accgacctgg 1800
cagaactgct ggtgctgctg ctgaaccagt ggacactgct gtaccacgat agtaacgtga 1860
agaatctgta tgagaaagtc cgatcacagc tgaagaacaa tgctaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcgaca acacctgtat ggagagcgtg aaaaatggca 1980
catacgatta tcccaagtat tccgaggaag ccaaactgaa cagagaggaa attgactctg 2040
ggggcgacat catcaagctg ctgaacgaac aggtcaacaa ggagatgcag agctccaatc 2100
tgtacatgtc catgtctagt tggtgttata cccactctct ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaacg 2220
agaacaatgt gcccgtccag ctgacatcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgactcagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagtaaag atcatgctac cttcaatttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agagccggaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 274
<211> 639
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(639)
<400> 274
atg gct atc atc tac ctg atc ctg ctg ttc act gct gtg cgg ggg gac 48
Met Ala Ile Ile Tyr Leu Ile Leu Leu Phe Thr Ala Val Arg Gly Asp
1 5 10 15
cag att tgc atc ggc tac cac gct aat aat tca act gag aag gtg gat 96
Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Lys Val Asp
20 25 30
act atc ctg gag cgg aac gtg acc gtc aca cac gct aaa gac att ggc 144
Thr Ile Leu Glu Arg Asn Val Thr Val Thr His Ala Lys Asp Ile Gly
35 40 45
agc gga ctg gtg ctg gca acc gga ctg agg aat gtc cca cag atc gag 192
Ser Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu
50 55 60
tcc cgc gga ctg ttc ggc gct atc gca ggg ttt att gaa ggc ggg tgg 240
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
65 70 75 80
cag gga atg att gat ggg tgg tac ggc tac cac cat tct aac gac caa 288
Gln Gly Met Ile Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln
85 90 95
gga agt ggc tac gcc gct gat aag gag agt act cag aaa gcc ttc gat 336
Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp
100 105 110
ggc atc acc aac atg gtg aat tca gtc att gag aag atg ggc agc gga 384
Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser Gly
115 120 125
ggc tcc gga acc gac ctg gca gaa ctg ctg gtg ctg ctg ctg aat cag 432
Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn Gln
130 135 140
tgg aca ctg ctg ttt cac gac tct aac gtg aag aat ctg tat gat aaa 480
Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys
145 150 155 160
gtc cgg atg cag ctg aga gac aac gtg aag gag ctg ggg aat gga tgc 528
Val Arg Met Gln Leu Arg Asp Asn Val Lys Glu Leu Gly Asn Gly Cys
165 170 175
ttc gaa ttt tac cat aag tgc gac gat gag tgt atg aac agt gtc aaa 576
Phe Glu Phe Tyr His Lys Cys Asp Asp Glu Cys Met Asn Ser Val Lys
180 185 190
aat ggc aca tac gat tat ccc aag tat gag gaa gag tca aaa ctg aac 624
Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Glu Glu Glu Ser Lys Leu Asn
195 200 205
cga aat gaa atc aag 639
Arg Asn Glu Ile Lys
210
<210> 275
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 275
Met Ala Ile Ile Tyr Leu Ile Leu Leu Phe Thr Ala Val Arg Gly Asp
1 5 10 15
Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Lys Val Asp
20 25 30
Thr Ile Leu Glu Arg Asn Val Thr Val Thr His Ala Lys Asp Ile Gly
35 40 45
Ser Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu
50 55 60
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
65 70 75 80
Gln Gly Met Ile Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln
85 90 95
Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp
100 105 110
Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser Gly
115 120 125
Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn Gln
130 135 140
Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys
145 150 155 160
Val Arg Met Gln Leu Arg Asp Asn Val Lys Glu Leu Gly Asn Gly Cys
165 170 175
Phe Glu Phe Tyr His Lys Cys Asp Asp Glu Cys Met Asn Ser Val Lys
180 185 190
Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Glu Glu Glu Ser Lys Leu Asn
195 200 205
Arg Asn Glu Ile Lys
210
<210> 276
<211> 639
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 276
cttgatttca tttcggttca gttttgactc ttcctcatac ttgggataat cgtatgtgcc 60
atttttgaca ctgttcatac actcatcgtc gcacttatgg taaaattcga agcatccatt 120
ccccagctcc ttcacgttgt ctctcagctg catccggact ttatcataca gattcttcac 180
gttagagtcg tgaaacagca gtgtccactg attcagcagc agcaccagca gttctgccag 240
gtcggttccg gagcctccgc tgcccatctt ctcaatgact gaattcacca tgttggtgat 300
gccatcgaag gctttctgag tactctcctt atcagcggcg tagccacttc cttggtcgtt 360
agaatggtgg tagccgtacc acccatcaat cattccctgc cacccgcctt caataaaccc 420
tgcgatagcg ccgaacagtc cgcgggactc gatctgtggg acattcctca gtccggttgc 480
cagcaccagt ccgctgccaa tgtctttagc gtgtgtgacg gtcacgttcc gctccaggat 540
agtatccacc ttctcagttg aattattagc gtggtagccg atgcaaatct ggtccccccg 600
cacagcagtg aacagcagga tcaggtagat gatagccat 639
<210> 277
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1149)
<400> 277
atg gct atc atc tac ctg atc ctg ctg ttc act gct gtg cgg ggg gac 48
Met Ala Ile Ile Tyr Leu Ile Leu Leu Phe Thr Ala Val Arg Gly Asp
1 5 10 15
cag att tgc atc ggc tac cac gct aat aat tca act gag aag gtg gat 96
Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Lys Val Asp
20 25 30
act atc ctg gag cgg aac gtg acc gtc aca cac gct aaa gac att ggc 144
Thr Ile Leu Glu Arg Asn Val Thr Val Thr His Ala Lys Asp Ile Gly
35 40 45
agc gga ctg gtg ctg gca acc gga ctg agg aat gtc cca cag atc gag 192
Ser Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu
50 55 60
tcc cgc gga ctg ttc ggc gct atc gca ggg ttt att gaa ggc ggg tgg 240
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
65 70 75 80
cag gga atg att gat ggg tgg tac ggc tac cac cat tct aac gac caa 288
Gln Gly Met Ile Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln
85 90 95
gga agt ggc tac gcc gct gat aag gag agt act cag aaa gcc ttc gat 336
Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp
100 105 110
ggc atc acc aac atg gtg aat tca gtc att gag aag atg ggc agc gga 384
Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser Gly
115 120 125
ggc tcc gga acc gac ctg gca gaa ctg ctg gtg ctg ctg ctg aat cag 432
Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn Gln
130 135 140
tgg aca ctg ctg ttt cac gac tct aac gtg aag aat ctg tat gat aaa 480
Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys
145 150 155 160
gtc cgg atg cag ctg aga gac aac gtg aag gag ctg ggg aat gga tgc 528
Val Arg Met Gln Leu Arg Asp Asn Val Lys Glu Leu Gly Asn Gly Cys
165 170 175
ttc gaa ttt tac cat aag tgc gac gat gag tgt atg aac agt gtc aaa 576
Phe Glu Phe Tyr His Lys Cys Asp Asp Glu Cys Met Asn Ser Val Lys
180 185 190
aat ggc aca tac gat tat ccc aag tat gag gaa gag tca aaa ctg aac 624
Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Glu Glu Glu Ser Lys Leu Asn
195 200 205
cga aat gaa atc aag agc ggg ggc gac atc atc aag ctg ctg aac gag 672
Arg Asn Glu Ile Lys Ser Gly Gly Asp Ile Ile Lys Leu Leu Asn Glu
210 215 220
caa gtg aat aag gaa atg cag agc tcc aac ctg tac atg tcc atg tct 720
Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser Met Ser
225 230 235 240
agt tgg tgt tat act cac tct ctg gat ggc gcc ggg ctg ttc ctg ttt 768
Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe Leu Phe
245 250 255
gac cac gca gcc gaa gag tac gag cat gct aag aaa ctg atc att ttc 816
Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile Ile Phe
260 265 270
ctg aac gaa aac aac gtg ccc gtc cag ctg aca tca atc agc gca cct 864
Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser Ala Pro
275 280 285
gag cat aag ttc gaa ggc ctg act cag atc ttt cag aaa gct tac gag 912
Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala Tyr Glu
290 295 300
cac gaa cag cat att tcc gag tct atc aac aat att gtg gac cac gcc 960
His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp His Ala
305 310 315 320
atc aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg tac gtg 1008
Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp Tyr Val
325 330 335
gcc gag cag cac gaa gag gaa gtc ctg ttt aag gac atc ctg gat aaa 1056
Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu Asp Lys
340 345 350
atc gag ctg att gga aac gaa aat cat ggc ctg tac ctg gca gac cag 1104
Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala Asp Gln
355 360 365
tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga tga 1149
Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 278
<211> 381
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 278
Met Ala Ile Ile Tyr Leu Ile Leu Leu Phe Thr Ala Val Arg Gly Asp
1 5 10 15
Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Lys Val Asp
20 25 30
Thr Ile Leu Glu Arg Asn Val Thr Val Thr His Ala Lys Asp Ile Gly
35 40 45
Ser Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Val Pro Gln Ile Glu
50 55 60
Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly Gly Trp
65 70 75 80
Gln Gly Met Ile Asp Gly Trp Tyr Gly Tyr His His Ser Asn Asp Gln
85 90 95
Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr Gln Lys Ala Phe Asp
100 105 110
Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser Gly
115 120 125
Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn Gln
130 135 140
Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Asp Lys
145 150 155 160
Val Arg Met Gln Leu Arg Asp Asn Val Lys Glu Leu Gly Asn Gly Cys
165 170 175
Phe Glu Phe Tyr His Lys Cys Asp Asp Glu Cys Met Asn Ser Val Lys
180 185 190
Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Glu Glu Glu Ser Lys Leu Asn
195 200 205
Arg Asn Glu Ile Lys Ser Gly Gly Asp Ile Ile Lys Leu Leu Asn Glu
210 215 220
Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser Met Ser
225 230 235 240
Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe Leu Phe
245 250 255
Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile Ile Phe
260 265 270
Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser Ala Pro
275 280 285
Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala Tyr Glu
290 295 300
His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp His Ala
305 310 315 320
Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp Tyr Val
325 330 335
Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu Asp Lys
340 345 350
Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala Asp Gln
355 360 365
Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 279
<211> 1149
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 279
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactggt ctgccaggta 60
caggccatga ttttcgtttc caatcagctc gattttatcc aggatgtcct taaacaggac 120
ttcctcttcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttgatg gcgtggtcca caatattgtt gatagactcg gaaatatgct gttcgtgctc 240
gtaagctttc tgaaagatct gagtcaggcc ttcgaactta tgctcaggtg cgctgattga 300
tgtcagctgg acgggcacgt tgttttcgtt caggaaaatg atcagtttct tagcatgctc 360
gtactcttcg gctgcgtggt caaacaggaa cagcccggcg ccatccagag agtgagtata 420
acaccaacta gacatggaca tgtacaggtt ggagctctgc atttccttat tcacttgctc 480
gttcagcagc ttgatgatgt cgcccccgct cttgatttca tttcggttca gttttgactc 540
ttcctcatac ttgggataat cgtatgtgcc atttttgaca ctgttcatac actcatcgtc 600
gcacttatgg taaaattcga agcatccatt ccccagctcc ttcacgttgt ctctcagctg 660
catccggact ttatcataca gattcttcac gttagagtcg tgaaacagca gtgtccactg 720
attcagcagc agcaccagca gttctgccag gtcggttccg gagcctccgc tgcccatctt 780
ctcaatgact gaattcacca tgttggtgat gccatcgaag gctttctgag tactctcctt 840
atcagcggcg tagccacttc cttggtcgtt agaatggtgg tagccgtacc acccatcaat 900
cattccctgc cacccgcctt caataaaccc tgcgatagcg ccgaacagtc cgcgggactc 960
gatctgtggg acattcctca gtccggttgc cagcaccagt ccgctgccaa tgtctttagc 1020
gtgtgtgacg gtcacgttcc gctccaggat agtatccacc ttctcagttg aattattagc 1080
gtggtagccg atgcaaatct ggtccccccg cacagcagtg aacagcagga tcaggtagat 1140
gatagccat 1149
<210> 280
<211> 5573
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 280
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catggctatc atctacctga tcctgctgtt cactgctgtg cggggggacc 1440
agatttgcat cggctaccac gctaataatt caactgagaa ggtggatact atcctggagc 1500
ggaacgtgac cgtcacacac gctaaagaca ttggcagcgg actggtgctg gcaaccggac 1560
tgaggaatgt cccacagatc gagtcccgcg gactgttcgg cgctatcgca gggtttattg 1620
aaggcgggtg gcagggaatg attgatgggt ggtacggcta ccaccattct aacgaccaag 1680
gaagtggcta cgccgctgat aaggagagta ctcagaaagc cttcgatggc atcaccaaca 1740
tggtgaattc agtcattgag aagatgggca gcggaggctc cggaaccgac ctggcagaac 1800
tgctggtgct gctgctgaat cagtggacac tgctgtttca cgactctaac gtgaagaatc 1860
tgtatgataa agtccggatg cagctgagag acaacgtgaa ggagctgggg aatggatgct 1920
tcgaatttta ccataagtgc gacgatgagt gtatgaacag tgtcaaaaat ggcacatacg 1980
attatcccaa gtatgaggaa gagtcaaaac tgaaccgaaa tgaaatcaag agcgggggcg 2040
acatcatcaa gctgctgaac gagcaagtga ataaggaaat gcagagctcc aacctgtaca 2100
tgtccatgtc tagttggtgt tatactcact ctctggatgg cgccgggctg ttcctgtttg 2160
accacgcagc cgaagagtac gagcatgcta agaaactgat cattttcctg aacgaaaaca 2220
acgtgcccgt ccagctgaca tcaatcagcg cacctgagca taagttcgaa ggcctgactc 2280
agatctttca gaaagcttac gagcacgaac agcatatttc cgagtctatc aacaatattg 2340
tggaccacgc catcaagagc aaagatcatg ctaccttcaa ctttctgcag tggtacgtgg 2400
ccgagcagca cgaagaggaa gtcctgttta aggacatcct ggataaaatc gagctgattg 2460
gaaacgaaaa tcatggcctg tacctggcag accagtatgt gaagggcatt gccaagtcca 2520
gaaaaagtgg gtcatgatga acacgtggga tccagatctg ctgtgccttc tagttgccag 2580
ccatctgttg tttgcccctc ccccgtgcct tccttgaccc tggaaggtgc cactcccact 2640
gtcctttcct aataaaatga ggaaattgca tcgcattgtc tgagtaggtg tcattctatt 2700
ctggggggtg gggtggggca ggacagcaag ggggaggatt gggaagacaa tagcaggcat 2760
gctggggatg cggtgggctc tatgggtacc caggtgctga agaattgacc cggttcctcc 2820
tgggccagaa agaagcaggc acatcccctt ctctgtgaca caccctgtcc acgcccctgg 2880
ttcttagttc cagccccact cataggacac tcatagctca ggagggctcc gccttcaatc 2940
ccacccgcta aagtacttgg agcggtctct ccctccctca tcagcccacc aaaccaaacc 3000
tagcctccaa gagtgggaag aaattaaagc aagataggct attaagtgca gagggagaga 3060
aaatgcctcc aacatgtgag gaagtaatga gagaaatcat agaattttaa ggccatgatt 3120
taaggccatc atggccttaa tcttccgctt cctcgctcac tgactcgctg cgctcggtcg 3180
ttcggctgcg gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat 3240
caggggataa cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta 3300
aaaaggccgc gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa 3360
atcgacgctc aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgtttc 3420
cccctggaag ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt 3480
ccgcctttct cccttcggga agcgtggcgc tttctcatag ctcacgctgt aggtatctca 3540
gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg 3600
accgctgcgc cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat 3660
cgccactggc agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta 3720
cagagttctt gaagtggtgg cctaactacg gctacactag aagaacagta tttggtatct 3780
gcgctctgct gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac 3840
aaaccaccgc tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa 3900
aaggatctca agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa 3960
actcacgtta agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt 4020
taaattaaaa atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca 4080
gttaccaatg cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca 4140
tagttgcctg actcgggggg ggggggcgct gaggtctgcc tcgtgaagaa ggtgttgctg 4200
actcatacca ggcctgaatc gccccatcat ccagccagaa agtgagggag ccacggttga 4260
tgagagcttt gttgtaggtg gaccagttgg tgattttgaa cttttgcttt gccacggaac 4320
ggtctgcgtt gtcgggaaga tgcgtgatct gatccttcaa ctcagcaaaa gttcgattta 4380
ttcaacaaag ccgccgtccc gtcaagtcag cgtaatgctc tgccagtgtt acaaccaatt 4440
aaccaattct gattagaaaa actcatcgag catcaaatga aactgcaatt tattcatatc 4500
aggattatca ataccatatt tttgaaaaag ccgtttctgt aatgaaggag aaaactcacc 4560
gaggcagttc cataggatgg caagatcctg gtatcggtct gcgattccga ctcgtccaac 4620
atcaatacaa cctattaatt tcccctcgtc aaaaataagg ttatcaagtg agaaatcacc 4680
atgagtgacg actgaatccg gtgagaatgg caaaagctta tgcatttctt tccagacttg 4740
ttcaacaggc cagccattac gctcgtcatc aaaatcactc gcatcaacca aaccgttatt 4800
cattcgtgat tgcgcctgag cgagacgaaa tacgcgatcg ctgttaaaag gacaattaca 4860
aacaggaatc gaatgcaacc ggcgcaggaa cactgccagc gcatcaacaa tattttcacc 4920
tgaatcagga tattcttcta atacctggaa tgctgttttc ccggggatcg cagtggtgag 4980
taaccatgca tcatcaggag tacggataaa atgcttgatg gtcggaagag gcataaattc 5040
cgtcagccag tttagtctga ccatctcatc tgtaacatca ttggcaacgc tacctttgcc 5100
atgtttcaga aacaactctg gcgcatcggg cttcccatac aatcgataga ttgtcgcacc 5160
tgattgcccg acattatcgc gagcccattt atacccatat aaatcagcat ccatgttgga 5220
atttaatcgc ggcctcgagc aagacgtttc ccgttgaata tggctcataa caccccttgt 5280
attactgttt atgtaagcag acagttttat tgttcatgat gatatatttt tatcttgtgc 5340
aatgtaacat cagagatttt gagacacaac gtggctttcc cccccccccc attattgaag 5400
catttatcag ggttattgtc tcatgagcgg atacatattt gaatgtattt agaaaaataa 5460
acaaataggg gttccgcgca catttccccg aaaagtgcca cctgacgtct aagaaaccat 5520
tattatcatg acattaacct ataaaaatag gcgtatcacg aggccctttc gtc 5573
<210> 281
<211> 654
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(654)
<400> 281
atg gaa aaa atc gtg ctg ctg ctg gct atc gtg tcc ctg gtg aag tcc 48
Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser
1 5 10 15
gac cag atc tgt att ggg tat cat gct aac aac tcc aca gaa cag gtg 96
Asp Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gln Val
20 25 30
gat act atc atg gag aag aac gtg acc gtc aca cac gct cag gac att 144
Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gln Asp Ile
35 40 45
gga tgg gga ctg gtc ctg gca acc gga ctg aga aat tca cca cag agg 192
Gly Trp Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg
50 55 60
gaa agc cgg aga aag aaa cgc gga ctg ttc ggc gct atc gca ggg ttt 240
Glu Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe
65 70 75 80
att gag ggc ggg tgg cag gga atg gtg gat ggg tgg tac ggc tac cac 288
Ile Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His
85 90 95
cat tcc aac gaa cag gga tct ggc tac gcc gct gat aag gag tct act 336
His Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr
100 105 110
cag aaa gct atc gac ggc gtg acc aac atg gtc aat agt atc att gat 384
Gln Lys Ala Ile Asp Gly Val Thr Asn Met Val Asn Ser Ile Ile Asp
115 120 125
aag atg ggc tct gga ggc agt gga acc gac ctg gca gag ctg ctg gtg 432
Lys Met Gly Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val
130 135 140
ctg ctg ctg aac cag tgg aca ctg ctg ttc cac gac tct aac gtg aag 480
Leu Leu Leu Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys
145 150 155 160
aat ctg tat gat aaa gtc cga ctg cag ctg cgg gac aac gcc aag gaa 528
Asn Leu Tyr Asp Lys Val Arg Leu Gln Leu Arg Asp Asn Ala Lys Glu
165 170 175
ctg ggg aat gga tgc ttc gag ttc tac cat aag tgc gat aac gaa tgt 576
Leu Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys
180 185 190
atg gag agc atc cga aac ggc aca tac aat tat ccc cag tat tcc gag 624
Met Glu Ser Ile Arg Asn Gly Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu
195 200 205
gaa gct agg ctg aaa cgc gag gaa att agc 654
Glu Ala Arg Leu Lys Arg Glu Glu Ile Ser
210 215
<210> 282
<211> 218
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 282
Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser
1 5 10 15
Asp Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gln Val
20 25 30
Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gln Asp Ile
35 40 45
Gly Trp Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg
50 55 60
Glu Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe
65 70 75 80
Ile Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His
85 90 95
His Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr
100 105 110
Gln Lys Ala Ile Asp Gly Val Thr Asn Met Val Asn Ser Ile Ile Asp
115 120 125
Lys Met Gly Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val
130 135 140
Leu Leu Leu Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys
145 150 155 160
Asn Leu Tyr Asp Lys Val Arg Leu Gln Leu Arg Asp Asn Ala Lys Glu
165 170 175
Leu Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys
180 185 190
Met Glu Ser Ile Arg Asn Gly Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu
195 200 205
Glu Ala Arg Leu Lys Arg Glu Glu Ile Ser
210 215
<210> 283
<211> 654
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 283
gctaatttcc tcgcgtttca gcctagcttc ctcggaatac tggggataat tgtatgtgcc 60
gtttcggatg ctctccatac attcgttatc gcacttatgg tagaactcga agcatccatt 120
ccccagttcc ttggcgttgt cccgcagctg cagtcggact ttatcataca gattcttcac 180
gttagagtcg tggaacagca gtgtccactg gttcagcagc agcaccagca gctctgccag 240
gtcggttcca ctgcctccag agcccatctt atcaatgata ctattgacca tgttggtcac 300
gccgtcgata gctttctgag tagactcctt atcagcggcg tagccagatc cctgttcgtt 360
ggaatggtgg tagccgtacc acccatccac cattccctgc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc cgcgtttctt tctccggctt tccctctgtg gtgaatttct 480
cagtccggtt gccaggacca gtccccatcc aatgtcctga gcgtgtgtga cggtcacgtt 540
cttctccatg atagtatcca cctgttctgt ggagttgtta gcatgatacc caatacagat 600
ctggtcggac ttcaccaggg acacgatagc cagcagcagc acgatttttt ccat 654
<210> 284
<211> 1164
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1164)
<400> 284
atg gaa aaa atc gtg ctg ctg ctg gct atc gtg tcc ctg gtg aag tcc 48
Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser
1 5 10 15
gac cag atc tgt att ggg tat cat gct aac aac tcc aca gaa cag gtg 96
Asp Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gln Val
20 25 30
gat act atc atg gag aag aac gtg acc gtc aca cac gct cag gac att 144
Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gln Asp Ile
35 40 45
gga tgg gga ctg gtc ctg gca acc gga ctg aga aat tca cca cag agg 192
Gly Trp Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg
50 55 60
gaa agc cgg aga aag aaa cgc gga ctg ttc ggc gct atc gca ggg ttt 240
Glu Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe
65 70 75 80
att gag ggc ggg tgg cag gga atg gtg gat ggg tgg tac ggc tac cac 288
Ile Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His
85 90 95
cat tcc aac gaa cag gga tct ggc tac gcc gct gat aag gag tct act 336
His Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr
100 105 110
cag aaa gct atc gac ggc gtg acc aac atg gtc aat agt atc att gat 384
Gln Lys Ala Ile Asp Gly Val Thr Asn Met Val Asn Ser Ile Ile Asp
115 120 125
aag atg ggc tct gga ggc agt gga acc gac ctg gca gag ctg ctg gtg 432
Lys Met Gly Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val
130 135 140
ctg ctg ctg aac cag tgg aca ctg ctg ttc cac gac tct aac gtg aag 480
Leu Leu Leu Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys
145 150 155 160
aat ctg tat gat aaa gtc cga ctg cag ctg cgg gac aac gcc aag gaa 528
Asn Leu Tyr Asp Lys Val Arg Leu Gln Leu Arg Asp Asn Ala Lys Glu
165 170 175
ctg ggg aat gga tgc ttc gag ttc tac cat aag tgc gat aac gaa tgt 576
Leu Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys
180 185 190
atg gag agc atc cga aac ggc aca tac aat tat ccc cag tat tcc gag 624
Met Glu Ser Ile Arg Asn Gly Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu
195 200 205
gaa gct agg ctg aaa cgc gag gaa att agc tcc ggg gga gac atc att 672
Glu Ala Arg Leu Lys Arg Glu Glu Ile Ser Ser Gly Gly Asp Ile Ile
210 215 220
aag ctg ctg aac gaa cag gtg aac aag gag atg cag tct agt aac ctg 720
Lys Leu Leu Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu
225 230 235 240
tac atg agt atg tca agc tgg tgt tat act cac tca ctg gat ggc gcc 768
Tyr Met Ser Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala
245 250 255
ggg ctg ttc ctg ttt gac cac gca gcc gag gaa tac gaa cat gct aag 816
Gly Leu Phe Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys
260 265 270
aaa ctg atc att ttc ctg aat gag aac aat gtg ccc gtc cag ctg aca 864
Lys Leu Ile Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr
275 280 285
tcc atc tct gca cct gaa cat aag ttc gag ggc ctg act cag atc ttt 912
Ser Ile Ser Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe
290 295 300
cag aaa gcc tac gaa cac gag cag cat att agt gag tca atc aac aat 960
Gln Lys Ala Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn
305 310 315 320
att gtg gac cac gcc atc aag agc aaa gat cat gct acc ttc aat ttt 1008
Ile Val Asp His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe
325 330 335
ctg cag tgg tac gtg gcc gag cag cac gag gaa gag gtc ctg ttt aag 1056
Leu Gln Trp Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys
340 345 350
gac atc ctg gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg 1104
Asp Ile Leu Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu
355 360 365
tac ctg gca gac cag tat gtg aag ggc att gcc aag tcc agg aaa agc 1152
Tyr Leu Ala Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser
370 375 380
ggg tcc tga tga 1164
Gly Ser
385
<210> 285
<211> 386
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 285
Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser
1 5 10 15
Asp Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gln Val
20 25 30
Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gln Asp Ile
35 40 45
Gly Trp Gly Leu Val Leu Ala Thr Gly Leu Arg Asn Ser Pro Gln Arg
50 55 60
Glu Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe
65 70 75 80
Ile Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr Gly Tyr His
85 90 95
His Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr
100 105 110
Gln Lys Ala Ile Asp Gly Val Thr Asn Met Val Asn Ser Ile Ile Asp
115 120 125
Lys Met Gly Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val
130 135 140
Leu Leu Leu Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys
145 150 155 160
Asn Leu Tyr Asp Lys Val Arg Leu Gln Leu Arg Asp Asn Ala Lys Glu
165 170 175
Leu Gly Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys
180 185 190
Met Glu Ser Ile Arg Asn Gly Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu
195 200 205
Glu Ala Arg Leu Lys Arg Glu Glu Ile Ser Ser Gly Gly Asp Ile Ile
210 215 220
Lys Leu Leu Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu
225 230 235 240
Tyr Met Ser Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala
245 250 255
Gly Leu Phe Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys
260 265 270
Lys Leu Ile Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr
275 280 285
Ser Ile Ser Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe
290 295 300
Gln Lys Ala Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn
305 310 315 320
Ile Val Asp His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe
325 330 335
Leu Gln Trp Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys
340 345 350
Asp Ile Leu Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu
355 360 365
Tyr Leu Ala Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser
370 375 380
Gly Ser
385
<210> 286
<211> 1164
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 286
tcatcaggac ccgcttttcc tggacttggc aatgcccttc acatactggt ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcttcctcg tgctgctcgg ccacgtacca ctgcagaaaa ttgaaggtag catgatcttt 180
gctcttgatg gcgtggtcca caatattgtt gattgactca ctaatatgct gctcgtgttc 240
gtaggctttc tgaaagatct gagtcaggcc ctcgaactta tgttcaggtg cagagatgga 300
tgtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct tagcatgttc 360
gtattcctcg gctgcgtggt caaacaggaa cagcccggcg ccatccagtg agtgagtata 420
acaccagctt gacatactca tgtacaggtt actagactgc atctccttgt tcacctgttc 480
gttcagcagc ttaatgatgt ctcccccgga gctaatttcc tcgcgtttca gcctagcttc 540
ctcggaatac tggggataat tgtatgtgcc gtttcggatg ctctccatac attcgttatc 600
gcacttatgg tagaactcga agcatccatt ccccagttcc ttggcgttgt cccgcagctg 660
cagtcggact ttatcataca gattcttcac gttagagtcg tggaacagca gtgtccactg 720
gttcagcagc agcaccagca gctctgccag gtcggttcca ctgcctccag agcccatctt 780
atcaatgata ctattgacca tgttggtcac gccgtcgata gctttctgag tagactcctt 840
atcagcggcg tagccagatc cctgttcgtt ggaatggtgg tagccgtacc acccatccac 900
cattccctgc cacccgccct caataaaccc tgcgatagcg ccgaacagtc cgcgtttctt 960
tctccggctt tccctctgtg gtgaatttct cagtccggtt gccaggacca gtccccatcc 1020
aatgtcctga gcgtgtgtga cggtcacgtt cttctccatg atagtatcca cctgttctgt 1080
ggagttgtta gcatgatacc caatacagat ctggtcggac ttcaccaggg acacgatagc 1140
cagcagcagc acgatttttt ccat 1164
<210> 287
<211> 5588
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 287
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catggaaaaa atcgtgctgc tgctggctat cgtgtccctg gtgaagtccg 1440
accagatctg tattgggtat catgctaaca actccacaga acaggtggat actatcatgg 1500
agaagaacgt gaccgtcaca cacgctcagg acattggatg gggactggtc ctggcaaccg 1560
gactgagaaa ttcaccacag agggaaagcc ggagaaagaa acgcggactg ttcggcgcta 1620
tcgcagggtt tattgagggc gggtggcagg gaatggtgga tgggtggtac ggctaccacc 1680
attccaacga acagggatct ggctacgccg ctgataagga gtctactcag aaagctatcg 1740
acggcgtgac caacatggtc aatagtatca ttgataagat gggctctgga ggcagtggaa 1800
ccgacctggc agagctgctg gtgctgctgc tgaaccagtg gacactgctg ttccacgact 1860
ctaacgtgaa gaatctgtat gataaagtcc gactgcagct gcgggacaac gccaaggaac 1920
tggggaatgg atgcttcgag ttctaccata agtgcgataa cgaatgtatg gagagcatcc 1980
gaaacggcac atacaattat ccccagtatt ccgaggaagc taggctgaaa cgcgaggaaa 2040
ttagctccgg gggagacatc attaagctgc tgaacgaaca ggtgaacaag gagatgcagt 2100
ctagtaacct gtacatgagt atgtcaagct ggtgttatac tcactcactg gatggcgccg 2160
ggctgttcct gtttgaccac gcagccgagg aatacgaaca tgctaagaaa ctgatcattt 2220
tcctgaatga gaacaatgtg cccgtccagc tgacatccat ctctgcacct gaacataagt 2280
tcgagggcct gactcagatc tttcagaaag cctacgaaca cgagcagcat attagtgagt 2340
caatcaacaa tattgtggac cacgccatca agagcaaaga tcatgctacc ttcaattttc 2400
tgcagtggta cgtggccgag cagcacgagg aagaggtcct gtttaaggac atcctggata 2460
aaatcgaact gattggaaac gagaatcatg gcctgtacct ggcagaccag tatgtgaagg 2520
gcattgccaa gtccaggaaa agcgggtcct gatgaacacg tgggatccag atctgctgtg 2580
ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt gaccctggaa 2640
ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca ttgtctgagt 2700
aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga ggattgggaa 2760
gacaatagca ggcatgctgg ggatgcggtg ggctctatgg gtacccaggt gctgaagaat 2820
tgacccggtt cctcctgggc cagaaagaag caggcacatc cccttctctg tgacacaccc 2880
tgtccacgcc cctggttctt agttccagcc ccactcatag gacactcata gctcaggagg 2940
gctccgcctt caatcccacc cgctaaagta cttggagcgg tctctccctc cctcatcagc 3000
ccaccaaacc aaacctagcc tccaagagtg ggaagaaatt aaagcaagat aggctattaa 3060
gtgcagaggg agagaaaatg cctccaacat gtgaggaagt aatgagagaa atcatagaat 3120
tttaaggcca tgatttaagg ccatcatggc cttaatcttc cgcttcctcg ctcactgact 3180
cgctgcgctc ggtcgttcgg ctgcggcgag cggtatcagc tcactcaaag gcggtaatac 3240
ggttatccac agaatcaggg gataacgcag gaaagaacat gtgagcaaaa ggccagcaaa 3300
aggccaggaa ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc cgcccccctg 3360
acgagcatca caaaaatcga cgctcaagtc agaggtggcg aaacccgaca ggactataaa 3420
gataccaggc gtttccccct ggaagctccc tcgtgcgctc tcctgttccg accctgccgc 3480
ttaccggata cctgtccgcc tttctccctt cgggaagcgt ggcgctttct catagctcac 3540
gctgtaggta tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac 3600
cccccgttca gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag tccaacccgg 3660
taagacacga cttatcgcca ctggcagcag ccactggtaa caggattagc agagcgaggt 3720
atgtaggcgg tgctacagag ttcttgaagt ggtggcctaa ctacggctac actagaagaa 3780
cagtatttgg tatctgcgct ctgctgaagc cagttacctt cggaaaaaga gttggtagct 3840
cttgatccgg caaacaaacc accgctggta gcggtggttt ttttgtttgc aagcagcaga 3900
ttacgcgcag aaaaaaagga tctcaagaag atcctttgat cttttctacg gggtctgacg 3960
ctcagtggaa cgaaaactca cgttaaggga ttttggtcat gagattatca aaaaggatct 4020
tcacctagat ccttttaaat taaaaatgaa gttttaaatc aatctaaagt atatatgagt 4080
aaacttggtc tgacagttac caatgcttaa tcagtgaggc acctatctca gcgatctgtc 4140
tatttcgttc atccatagtt gcctgactcg gggggggggg gcgctgaggt ctgcctcgtg 4200
aagaaggtgt tgctgactca taccaggcct gaatcgcccc atcatccagc cagaaagtga 4260
gggagccacg gttgatgaga gctttgttgt aggtggacca gttggtgatt ttgaactttt 4320
gctttgccac ggaacggtct gcgttgtcgg gaagatgcgt gatctgatcc ttcaactcag 4380
caaaagttcg atttattcaa caaagccgcc gtcccgtcaa gtcagcgtaa tgctctgcca 4440
gtgttacaac caattaacca attctgatta gaaaaactca tcgagcatca aatgaaactg 4500
caatttattc atatcaggat tatcaatacc atatttttga aaaagccgtt tctgtaatga 4560
aggagaaaac tcaccgaggc agttccatag gatggcaaga tcctggtatc ggtctgcgat 4620
tccgactcgt ccaacatcaa tacaacctat taatttcccc tcgtcaaaaa taaggttatc 4680
aagtgagaaa tcaccatgag tgacgactga atccggtgag aatggcaaaa gcttatgcat 4740
ttctttccag acttgttcaa caggccagcc attacgctcg tcatcaaaat cactcgcatc 4800
aaccaaaccg ttattcattc gtgattgcgc ctgagcgaga cgaaatacgc gatcgctgtt 4860
aaaaggacaa ttacaaacag gaatcgaatg caaccggcgc aggaacactg ccagcgcatc 4920
aacaatattt tcacctgaat caggatattc ttctaatacc tggaatgctg ttttcccggg 4980
gatcgcagtg gtgagtaacc atgcatcatc aggagtacgg ataaaatgct tgatggtcgg 5040
aagaggcata aattccgtca gccagtttag tctgaccatc tcatctgtaa catcattggc 5100
aacgctacct ttgccatgtt tcagaaacaa ctctggcgca tcgggcttcc catacaatcg 5160
atagattgtc gcacctgatt gcccgacatt atcgcgagcc catttatacc catataaatc 5220
agcatccatg ttggaattta atcgcggcct cgagcaagac gtttcccgtt gaatatggct 5280
cataacaccc cttgtattac tgtttatgta agcagacagt tttattgttc atgatgatat 5340
atttttatct tgtgcaatgt aacatcagag attttgagac acaacgtggc tttccccccc 5400
cccccattat tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg 5460
tatttagaaa aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga 5520
cgtctaagaa accattatta tcatgacatt aacctataaa aataggcgta tcacgaggcc 5580
ctttcgtc 5588
<210> 288
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 288
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca tac aac gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 289
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 289
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 290
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 290
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcagcagc agcaccagca gctcagcgtt 240
gtatgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 291
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 291
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca tac aac gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 292
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 292
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 293
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 293
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaaatcca gagtccgctc 720
gttcagcagc agcaccagca gctcagcgtt gtatgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 294
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 294
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acatacaacg 1800
ctgagctgct ggtgctgctg ctgaacgagc ggactctgga tttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 295
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 295
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 296
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 296
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 297
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 297
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 298
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 298
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 299
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 299
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 300
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 300
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaaatcca gagtccgctc 720
gttcagcagc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 301
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 301
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acagacctgg 1800
ctgagctgct ggtgctgctg ctgaacgagc ggactctgga tttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 302
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 302
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atc gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Ile Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg atc 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 303
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 303
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Ile Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 304
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 304
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttgatcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacga tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 305
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 305
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atc gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Ile Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg atc 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 306
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 306
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Ile Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 307
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 307
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaaatcca gagtccgctc 720
gttgatcagc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacga tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 308
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 308
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatcgt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acagacctgg 1800
ctgagctgct ggtgctgctg atcaacgagc ggactctgga tttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 309
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 309
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac ctg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg atc 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 310
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 310
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 311
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 311
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttgatcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca ggttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 312
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 312
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac ctg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg atc 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 313
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 313
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Ile
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 314
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 314
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaaatcca gagtccgctc 720
gttgatcagc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacca ggttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 315
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 315
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacctggt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acagacctgg 1800
ctgagctgct ggtgctgctg atcaacgagc ggactctgga tttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 316
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 316
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac ctg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 317
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 317
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 318
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 318
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca ggttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 319
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 319
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac ctg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 320
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 320
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Leu Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 321
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 321
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaaatcca gagtccgctc 720
gttcagcagc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacca ggttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 322
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 322
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacctggt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acagacctgg 1800
ctgagctgct ggtgctgctg ctgaacgagc ggactctgga tttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 323
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 323
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg atg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Met
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 324
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 324
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Met
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 325
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 325
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcatcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 326
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 326
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg atg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Met
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 327
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 327
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Met
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 328
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 328
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaaatcca gagtccgctc 720
gttcatcagc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 329
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 329
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acagacctgg 1800
ctgagctgct ggtgctgctg atgaacgagc ggactctgga tttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 330
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 330
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac cag gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Gln Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg cag 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Gln
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 331
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 331
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Gln Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Gln
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 332
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 332
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttctgcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacct ggttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 333
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 333
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac cag gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Gln Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg cag 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Gln
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 334
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 334
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Gln Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Gln
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 335
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 335
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaaatcca gagtccgctc 720
gttctgcagc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacct ggttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 336
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 336
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaaccaggt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acagacctgg 1800
ctgagctgct ggtgctgctg cagaacgagc ggactctgga tttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 337
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 337
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc aac tca act aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr Asn Ser Thr Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 338
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 338
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr Asn Ser Thr Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 339
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 339
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaaatcca gagtccgctc gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattagttga gttggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 340
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 340
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc aac tca act aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr Asn Ser Thr Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac gag cgg act ctg gat ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 341
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 341
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr Asn Ser Thr Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 342
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 342
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaaatcca gagtccgctc 720
gttcagcagc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattagttga 1020
gttggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 343
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 343
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc accaactcaa ctaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acagacctgg 1800
ctgagctgct ggtgctgctg ctgaacgagc ggactctgga tttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 344
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 344
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc att ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Ile Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg atg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Met Leu
130 135 140
aac cag ttc act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Phe Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 345
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 345
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Ile Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Met Leu
130 135 140
Asn Gln Phe Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 346
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 346
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtgaactg gttcagcatc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccagaat 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 347
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 347
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc att ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Ile Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg atg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Met Leu
130 135 140
aac cag ttc act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Phe Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 348
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 348
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Ile Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Met Leu
130 135 140
Asn Gln Phe Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 349
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 349
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaacagca gagtgaactg 720
gttcagcatc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccagaat ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 350
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 350
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccattc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcagcgg aggctccgga acagacctgg 1800
ctgagctgct ggtgctgatg ctgaaccagt tcactctgct gttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 351
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 351
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
aat gga aca ggc gga gct gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Asn Gly Thr Gly Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 352
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 352
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Asn Gly Thr Gly Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 353
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 353
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtcagctccg cctgttccat tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 354
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 354
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
aat gga aca ggc gga gct gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Asn Gly Thr Gly Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 355
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 355
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Asn Gly Thr Gly Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 356
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 356
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaacagca gagtccactg 720
gttcagcagc agcaccagca gctcagccag gtcagctccg cctgttccat tgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 357
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 357
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcaatgg aacaggcgga gctgacctgg 1800
ctgagctgct ggtgctgctg ctgaaccagt ggactctgct gttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 358
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 358
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
gga aat ggc act gga gct gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 359
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 359
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 360
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 360
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtcagctcca gtgccatttc cgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 361
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 361
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
gga aat ggc act gga gct gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 362
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 362
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 363
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 363
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaacagca gagtccactg 720
gttcagcagc agcaccagca gctcagccag gtcagctcca gtgccatttc cgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 364
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 364
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcggaaa tggcactgga gctgacctgg 1800
ctgagctgct ggtgctgctg ctgaaccagt ggactctgct gttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 365
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 365
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc aac gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Asn Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 366
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 366
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Asn Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 367
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 367
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtctgttccg ttgcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 368
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 368
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
agc gga ggc aac gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Ser Gly Gly Asn Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 369
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 369
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Asn Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 370
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 370
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaacagca gagtccactg 720
gttcagcagc agcaccagca gctcagccag gtctgttccg ttgcctccgc tgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 371
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 371
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac catcagaatg 1680
agcagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcagcgg aggcaacgga acagacctgg 1800
ctgagctgct ggtgctgctg ctgaaccagt ggactctgct gttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgcag agctccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 372
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 372
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat aac aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
acc cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
gga aat ggc act gga gct gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 373
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 373
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 374
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 374
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtcagctcca gtgccatttc cgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgggtatt 360
gttatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 375
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 375
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat aac aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
acc cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
gga aat ggc act gga gct gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg aac agc acc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Asn Ser Thr Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 376
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 376
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Asn Ser Thr Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 377
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 377
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggtgctgttc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaacagca gagtccactg 720
gttcagcagc agcaccagca gctcagccag gtcagctcca gtgccatttc cgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgggtatt gttatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 378
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 378
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac cataacaata 1680
cccagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcggaaa tggcactgga gctgacctgg 1800
ctgagctgct ggtgctgctg ctgaaccagt ggactctgct gttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgaac agcaccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtccag ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 379
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(645)
<400> 379
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat aac aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
acc cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
gga aat ggc act gga gct gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac 645
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 380
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 380
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp
210 215
<210> 381
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 381
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtcagctcca gtgccatttc cgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgggtatt 360
gttatggtgg tagccgtacc acccgtccac cattcctgtc cacccgccct caataaaccc 420
tgcgatagcg ccgaacagtc ctcttgtttc ccgctgtggg atgttgcgca gtccggtgac 480
catcctcagt ccgctgccca gattcactga gtgggtgaca gtcacgttct tctccaggac 540
ggtatccact gtgtcggtgg agttgtttgc gtgatagccg atgcagatag tgtcagcgta 600
ggttgcggta aaagtacaca gcaggaccag cagtttggcc ttcat 645
<210> 382
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1155)
<400> 382
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac atc cca cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
cgg gaa aca aga gga ctg ttc ggc gct atc gca ggg ttt att gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggg tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat aac aat 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
acc cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca 336
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
gga aat ggc act gga gct gac ctg gct gag ctg ctg gtg ctg ctg ctg 432
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat 480
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
gga tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg 672
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
aac gaa cag gtg aac aag gag atg aac agc acc aac ctg tac atg agt 720
Asn Glu Gln Val Asn Lys Glu Met Asn Ser Thr Asn Leu Tyr Met Ser
225 230 235 240
atg tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc 768
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
ctg ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc 816
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
att ttc ctg aat gag aac aat gtg ccc gtc aac ctg act tca atc agc 864
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Asn Leu Thr Ser Ile Ser
275 280 285
gcc cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct 912
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
tac gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac 960
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
cac gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg 1008
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
tac gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg 1056
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
gat aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca 1104
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
gat cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga 1152
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
tga 1155
<210> 383
<211> 383
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 383
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Asn Asn
85 90 95
Thr Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Gly Asn Gly Thr Gly Ala Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu
210 215 220
Asn Glu Gln Val Asn Lys Glu Met Asn Ser Thr Asn Leu Tyr Met Ser
225 230 235 240
Met Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe
245 250 255
Leu Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile
260 265 270
Ile Phe Leu Asn Glu Asn Asn Val Pro Val Asn Leu Thr Ser Ile Ser
275 280 285
Ala Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala
290 295 300
Tyr Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp
305 310 315 320
His Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp
325 330 335
Tyr Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu
340 345 350
Asp Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala
355 360 365
Asp Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
370 375 380
<210> 384
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 384
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcaggttg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggtgctgttc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaacagca gagtccactg 720
gttcagcagc agcaccagca gctcagccag gtcagctcca gtgccatttc cgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgggtatt gttatggtgg tagccgtacc acccgtccac 900
cattcctgtc cacccgccct caataaaccc tgcgatagcg ccgaacagtc ctcttgtttc 960
ccgctgtggg atgttgcgca gtccggtgac catcctcagt ccgctgccca gattcactga 1020
gtgggtgaca gtcacgttct tctccaggac ggtatccact gtgtcggtgg agttgtttgc 1080
gtgatagccg atgcagatag tgtcagcgta ggttgcggta aaagtacaca gcaggaccag 1140
cagtttggcc ttcat 1155
<210> 385
<211> 5579
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 385
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacatccca cagcgggaaa caagaggact gttcggcgct atcgcagggt 1620
ttattgaggg cgggtggaca ggaatggtgg acgggtggta cggctaccac cataacaata 1680
cccagggcag cggctacgcc gctgatcaga agtctacaca gaacgcaatc aatggcatta 1740
ctaacatggt gaattctgtc atcgaaaaaa tgggcggaaa tggcactgga gctgacctgg 1800
ctgagctgct ggtgctgctg ctgaaccagt ggactctgct gttccacgat agcaacgtga 1860
agaatctgta tgagaaggtc aaatcccagc tgaagaacaa tgccaaagaa atcgggaatg 1920
gatgcttcga gttttaccat aagtgcaaca atgaatgtat ggagtctgtg aagaacggca 1980
cttacgacta tcccaaatat tctgaagaga gtaagctgaa tcgagagaaa attgacagtg 2040
ggggcgacat catcaagctg ctgaacgaac aggtgaacaa ggagatgaac agcaccaacc 2100
tgtacatgag tatgtctagt tggtgttata cacactcact ggacggcgct gggctgttcc 2160
tgtttgatca cgcagccgag gaatacgaac atgcaaagaa actgatcatt ttcctgaatg 2220
agaacaatgt gcccgtcaac ctgacttcaa tcagcgcccc tgaacataag ttcgagggcc 2280
tgacccagat ctttcagaaa gcttacgaac acgagcagca tatttccgaa tctatcaaca 2340
atattgtgga ccacgccatt aagagcaaag atcatgctac cttcaacttt ctgcagtggt 2400
acgtggccga gcagcacgag gaggaggtcc tgtttaagga catcctggat aaaatcgaac 2460
tgattggaaa cgagaatcat ggcctgtacc tggcagatca gtatgtgaag ggcattgcca 2520
agtccagaaa aagtgggtca tgatgaacac gtgggatcca gatctgctgt gccttctagt 2580
tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact 2640
cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat 2700
tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc 2760
aggcatgctg gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt 2820
tcctcctggg ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc 2880
ccctggttct tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct 2940
tcaatcccac ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac 3000
caaacctagc ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg 3060
gagagaaaat gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc 3120
atgatttaag gccatcatgg ccttaatctt ccgcttcctc gctcactgac tcgctgcgct 3180
cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca 3240
cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga 3300
accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc 3360
acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg 3420
cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat 3480
acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt 3540
atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc 3600
agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg 3660
acttatcgcc actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg 3720
gtgctacaga gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg 3780
gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg 3840
gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca 3900
gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga 3960
acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga 4020
tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt 4080
ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt 4140
catccatagt tgcctgactc gggggggggg ggcgctgagg tctgcctcgt gaagaaggtg 4200
ttgctgactc ataccaggcc tgaatcgccc catcatccag ccagaaagtg agggagccac 4260
ggttgatgag agctttgttg taggtggacc agttggtgat tttgaacttt tgctttgcca 4320
cggaacggtc tgcgttgtcg ggaagatgcg tgatctgatc cttcaactca gcaaaagttc 4380
gatttattca acaaagccgc cgtcccgtca agtcagcgta atgctctgcc agtgttacaa 4440
ccaattaacc aattctgatt agaaaaactc atcgagcatc aaatgaaact gcaatttatt 4500
catatcagga ttatcaatac catatttttg aaaaagccgt ttctgtaatg aaggagaaaa 4560
ctcaccgagg cagttccata ggatggcaag atcctggtat cggtctgcga ttccgactcg 4620
tccaacatca atacaaccta ttaatttccc ctcgtcaaaa ataaggttat caagtgagaa 4680
atcaccatga gtgacgactg aatccggtga gaatggcaaa agcttatgca tttctttcca 4740
gacttgttca acaggccagc cattacgctc gtcatcaaaa tcactcgcat caaccaaacc 4800
gttattcatt cgtgattgcg cctgagcgag acgaaatacg cgatcgctgt taaaaggaca 4860
attacaaaca ggaatcgaat gcaaccggcg caggaacact gccagcgcat caacaatatt 4920
ttcacctgaa tcaggatatt cttctaatac ctggaatgct gttttcccgg ggatcgcagt 4980
ggtgagtaac catgcatcat caggagtacg gataaaatgc ttgatggtcg gaagaggcat 5040
aaattccgtc agccagttta gtctgaccat ctcatctgta acatcattgg caacgctacc 5100
tttgccatgt ttcagaaaca actctggcgc atcgggcttc ccatacaatc gatagattgt 5160
cgcacctgat tgcccgacat tatcgcgagc ccatttatac ccatataaat cagcatccat 5220
gttggaattt aatcgcggcc tcgagcaaga cgtttcccgt tgaatatggc tcataacacc 5280
ccttgtatta ctgtttatgt aagcagacag ttttattgtt catgatgata tatttttatc 5340
ttgtgcaatg taacatcaga gattttgaga cacaacgtgg ctttcccccc ccccccatta 5400
ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa 5460
aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga 5520
aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 5579
<210> 386
<211> 384
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(384)
<400> 386
atg aag gcc aag ctg ctg gtg ctc ctg tgc acc ttc acc gcc acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gcc gac acc atc tgc atc ggc tac cac gcc aac aac agc acc gac acc 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtg ctg gaa aag aac gtg acc gtg acc cac agc gtg aac 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc ggc ctg cgg atg gtg aca ggc ctg cgg aac atc ccc cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
aga gag aca cgg ggc ctg ttc ggc gcc att gcc ggc ttt atc gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggc tgg acc ggc atg gtg gac ggg tgg tac ggc tac cac cac cag aac 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gcc gac cag aag tcc acc cag aac gcc 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aac ggc atc acc aac atg gtg aac agc gtg atc gag aag atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
<210> 387
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 387
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
<210> 388
<211> 384
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 388
gcccatcttc tcgatcacgc tgttcaccat gttggtgatg ccgttgatgg cgttctgggt 60
ggacttctgg tcggcggcgt agccgctgcc ctgctcgttc tggtggtggt agccgtacca 120
cccgtccacc atgccggtcc agccgccctc gataaagccg gcaatggcgc cgaacaggcc 180
ccgtgtctct ctctggggga tgttccgcag gcctgtcacc atccgcaggc cgctgcccag 240
gttcacgctg tgggtcacgg tcacgttctt ttccagcacg gtatccacgg tgtcggtgct 300
gttgttggcg tggtagccga tgcagatggt gtcggcgtag gtggcggtga aggtgcacag 360
gagcaccagc agcttggcct tcat 384
<210> 389
<211> 1110
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1110)
<400> 389
atg aag gcc aag ctg ctg gtg ctc ctg tgc acc ttc acc gcc acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gcc gac acc atc tgc atc ggc tac cac gcc aac aac agc acc gac acc 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtg ctg gaa aag aac gtg acc gtg acc cac agc gtg aac 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc ggc ctg cgg atg gtg aca ggc ctg cgg aac atc ccc cag 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
aga gag aca cgg ggc ctg ttc ggc gcc att gcc ggc ttt atc gag ggc 240
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
ggc tgg acc ggc atg gtg gac ggg tgg tac ggc tac cac cac cag aac 288
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
gag cag ggc agc ggc tac gcc gcc gac cag aag tcc acc cag aac gcc 336
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
atc aac ggc atc acc aac atg gtg aac agc gtg atc gag aag atg ggc 384
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
tcc ggc ggc agc ggc acc gat ctg gct gaa ctg ctg gtc ctg ctg ctg 432
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
aac gag cgg acc ctg gac ttc cac gac agc aac gtg aag aac ctg tac 480
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
gag aaa gtg aag tcc cag ctg aag aac aac gcc aaa gag atc ggc aac 528
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
ggc tgc ttc gag ttc tac cac aag tgc aac aac gag tgc atg gaa agc 576
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
gtg aag aac ggc acc tac gac tac ccc aag tac agc gag gaa agc aag 624
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
ctg aac cgc gag gga ggc atg caa atc tac gag ggc aag ctg aca gcc 672
Leu Asn Arg Glu Gly Gly Met Gln Ile Tyr Glu Gly Lys Leu Thr Ala
210 215 220
gag ggc ctg aga ttc ggc atc gtg gcc agc cgg ttc aac cac gcc ctg 720
Glu Gly Leu Arg Phe Gly Ile Val Ala Ser Arg Phe Asn His Ala Leu
225 230 235 240
gtg gac aga ctg gtg gaa ggc gcc atc gac tgc atc gtg cgg cac ggc 768
Val Asp Arg Leu Val Glu Gly Ala Ile Asp Cys Ile Val Arg His Gly
245 250 255
ggc aga gaa gag gac atc acc ctg gtc cgc gtg ccc ggc agc tgg gaa 816
Gly Arg Glu Glu Asp Ile Thr Leu Val Arg Val Pro Gly Ser Trp Glu
260 265 270
att cct gtg gct gcc ggc gag ctg gcc cgg aaa gag gat atc gac gcc 864
Ile Pro Val Ala Ala Gly Glu Leu Ala Arg Lys Glu Asp Ile Asp Ala
275 280 285
gtc atc gcc atc ggc gtg ctg atc aga ggc gcc acc ccc cac ttc gac 912
Val Ile Ala Ile Gly Val Leu Ile Arg Gly Ala Thr Pro His Phe Asp
290 295 300
tat atc gcc agc gag gtg tcc aag ggc ctg gcc aac ctg agc ctg gaa 960
Tyr Ile Ala Ser Glu Val Ser Lys Gly Leu Ala Asn Leu Ser Leu Glu
305 310 315 320
ctg cgg aag ccc atc acc ttc gga gtg atc acc gcc gac acc ctg gaa 1008
Leu Arg Lys Pro Ile Thr Phe Gly Val Ile Thr Ala Asp Thr Leu Glu
325 330 335
cag gcc atc gag aga gcc ggc acc aag cac ggc aac aag gga tgg gaa 1056
Gln Ala Ile Glu Arg Ala Gly Thr Lys His Gly Asn Lys Gly Trp Glu
340 345 350
gcc gcc ctg agc gcc atc gag atg gcc aat ctg ttc aag agc ctg cgc 1104
Ala Ala Leu Ser Ala Ile Glu Met Ala Asn Leu Phe Lys Ser Leu Arg
355 360 365
tga tga 1110
<210> 390
<211> 368
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 390
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Ile Pro Gln
50 55 60
Arg Glu Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Gly
65 70 75 80
Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn
85 90 95
Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala
100 105 110
Ile Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly
115 120 125
Ser Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu
130 135 140
Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr
145 150 155 160
Glu Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn
165 170 175
Gly Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser
180 185 190
Val Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys
195 200 205
Leu Asn Arg Glu Gly Gly Met Gln Ile Tyr Glu Gly Lys Leu Thr Ala
210 215 220
Glu Gly Leu Arg Phe Gly Ile Val Ala Ser Arg Phe Asn His Ala Leu
225 230 235 240
Val Asp Arg Leu Val Glu Gly Ala Ile Asp Cys Ile Val Arg His Gly
245 250 255
Gly Arg Glu Glu Asp Ile Thr Leu Val Arg Val Pro Gly Ser Trp Glu
260 265 270
Ile Pro Val Ala Ala Gly Glu Leu Ala Arg Lys Glu Asp Ile Asp Ala
275 280 285
Val Ile Ala Ile Gly Val Leu Ile Arg Gly Ala Thr Pro His Phe Asp
290 295 300
Tyr Ile Ala Ser Glu Val Ser Lys Gly Leu Ala Asn Leu Ser Leu Glu
305 310 315 320
Leu Arg Lys Pro Ile Thr Phe Gly Val Ile Thr Ala Asp Thr Leu Glu
325 330 335
Gln Ala Ile Glu Arg Ala Gly Thr Lys His Gly Asn Lys Gly Trp Glu
340 345 350
Ala Ala Leu Ser Ala Ile Glu Met Ala Asn Leu Phe Lys Ser Leu Arg
355 360 365
<210> 391
<211> 1110
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 391
tcatcagcgc aggctcttga acagattggc catctcgatg gcgctcaggg cggcttccca 60
tcccttgttg ccgtgcttgg tgccggctct ctcgatggcc tgttccaggg tgtcggcggt 120
gatcactccg aaggtgatgg gcttccgcag ttccaggctc aggttggcca ggcccttgga 180
cacctcgctg gcgatatagt cgaagtgggg ggtggcgcct ctgatcagca cgccgatggc 240
gatgacggcg tcgatatcct ctttccgggc cagctcgccg gcagccacag gaatttccca 300
gctgccgggc acgcggacca gggtgatgtc ctcttctctg ccgccgtgcc gcacgatgca 360
gtcgatggcg ccttccacca gtctgtccac cagggcgtgg ttgaaccggc tggccacgat 420
gccgaatctc aggccctcgg ctgtcagctt gccctcgtag atttgcatgc ctccctcgcg 480
gttcagcttg ctttcctcgc tgtacttggg gtagtcgtag gtgccgttct tcacgctttc 540
catgcactcg ttgttgcact tgtggtagaa ctcgaagcag ccgttgccga tctctttggc 600
gttgttcttc agctgggact tcactttctc gtacaggttc ttcacgttgc tgtcgtggaa 660
gtccagggtc cgctcgttca gcagcaggac cagcagttca gccagatcgg tgccgctgcc 720
gccggagccc atcttctcga tcacgctgtt caccatgttg gtgatgccgt tgatggcgtt 780
ctgggtggac ttctggtcgg cggcgtagcc gctgccctgc tcgttctggt ggtggtagcc 840
gtaccacccg tccaccatgc cggtccagcc gccctcgata aagccggcaa tggcgccgaa 900
caggccccgt gtctctctct gggggatgtt ccgcaggcct gtcaccatcc gcaggccgct 960
gcccaggttc acgctgtggg tcacggtcac gttcttttcc agcacggtat ccacggtgtc 1020
ggtgctgttg ttggcgtggt agccgatgca gatggtgtcg gcgtaggtgg cggtgaaggt 1080
gcacaggagc accagcagct tggccttcat 1110
<210> 392
<211> 5528
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 392
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
ccaccatgaa ggccaagctg ctggtgctcc tgtgcacctt caccgccacc tacgccgaca 1440
ccatctgcat cggctaccac gccaacaaca gcaccgacac cgtggatacc gtgctggaaa 1500
agaacgtgac cgtgacccac agcgtgaacc tgggcagcgg cctgcggatg gtgacaggcc 1560
tgcggaacat cccccagaga gagacacggg gcctgttcgg cgccattgcc ggctttatcg 1620
agggcggctg gaccggcatg gtggacgggt ggtacggcta ccaccaccag aacgagcagg 1680
gcagcggcta cgccgccgac cagaagtcca cccagaacgc catcaacggc atcaccaaca 1740
tggtgaacag cgtgatcgag aagatgggct ccggcggcag cggcaccgat ctggctgaac 1800
tgctggtcct gctgctgaac gagcggaccc tggacttcca cgacagcaac gtgaagaacc 1860
tgtacgagaa agtgaagtcc cagctgaaga acaacgccaa agagatcggc aacggctgct 1920
tcgagttcta ccacaagtgc aacaacgagt gcatggaaag cgtgaagaac ggcacctacg 1980
actaccccaa gtacagcgag gaaagcaagc tgaaccgcga gggaggcatg caaatctacg 2040
agggcaagct gacagccgag ggcctgagat tcggcatcgt ggccagccgg ttcaaccacg 2100
ccctggtgga cagactggtg gaaggcgcca tcgactgcat cgtgcggcac ggcggcagag 2160
aagaggacat caccctggtc cgcgtgcccg gcagctggga aattcctgtg gctgccggcg 2220
agctggcccg gaaagaggat atcgacgccg tcatcgccat cggcgtgctg atcagaggcg 2280
ccacccccca cttcgactat atcgccagcg aggtgtccaa gggcctggcc aacctgagcc 2340
tggaactgcg gaagcccatc accttcggag tgatcaccgc cgacaccctg gaacaggcca 2400
tcgagagagc cggcaccaag cacggcaaca agggatggga agccgccctg agcgccatcg 2460
agatggccaa tctgttcaag agcctgcgct gatgaacacg tgggatccag atctgctgtg 2520
ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt gaccctggaa 2580
ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca ttgtctgagt 2640
aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga ggattgggaa 2700
gacaatagca ggcatgctgg ggatgcggtg ggctctatgg gtacccaggt gctgaagaat 2760
tgacccggtt cctcctgggc cagaaagaag caggcacatc cccttctctg tgacacaccc 2820
tgtccacgcc cctggttctt agttccagcc ccactcatag gacactcata gctcaggagg 2880
gctccgcctt caatcccacc cgctaaagta cttggagcgg tctctccctc cctcatcagc 2940
ccaccaaacc aaacctagcc tccaagagtg ggaagaaatt aaagcaagat aggctattaa 3000
gtgcagaggg agagaaaatg cctccaacat gtgaggaagt aatgagagaa atcatagaat 3060
tttaaggcca tgatttaagg ccatcatggc cttaatcttc cgcttcctcg ctcactgact 3120
cgctgcgctc ggtcgttcgg ctgcggcgag cggtatcagc tcactcaaag gcggtaatac 3180
ggttatccac agaatcaggg gataacgcag gaaagaacat gtgagcaaaa ggccagcaaa 3240
aggccaggaa ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc cgcccccctg 3300
acgagcatca caaaaatcga cgctcaagtc agaggtggcg aaacccgaca ggactataaa 3360
gataccaggc gtttccccct ggaagctccc tcgtgcgctc tcctgttccg accctgccgc 3420
ttaccggata cctgtccgcc tttctccctt cgggaagcgt ggcgctttct catagctcac 3480
gctgtaggta tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac 3540
cccccgttca gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag tccaacccgg 3600
taagacacga cttatcgcca ctggcagcag ccactggtaa caggattagc agagcgaggt 3660
atgtaggcgg tgctacagag ttcttgaagt ggtggcctaa ctacggctac actagaagaa 3720
cagtatttgg tatctgcgct ctgctgaagc cagttacctt cggaaaaaga gttggtagct 3780
cttgatccgg caaacaaacc accgctggta gcggtggttt ttttgtttgc aagcagcaga 3840
ttacgcgcag aaaaaaagga tctcaagaag atcctttgat cttttctacg gggtctgacg 3900
ctcagtggaa cgaaaactca cgttaaggga ttttggtcat gagattatca aaaaggatct 3960
tcacctagat ccttttaaat taaaaatgaa gttttaaatc aatctaaagt atatatgagt 4020
aaacttggtc tgacagttac caatgcttaa tcagtgaggc acctatctca gcgatctgtc 4080
tatttcgttc atccatagtt gcctgactcg gggggggggg gcgctgaggt ctgcctcgtg 4140
aagaaggtgt tgctgactca taccaggcct gaatcgcccc atcatccagc cagaaagtga 4200
gggagccacg gttgatgaga gctttgttgt aggtggacca gttggtgatt ttgaactttt 4260
gctttgccac ggaacggtct gcgttgtcgg gaagatgcgt gatctgatcc ttcaactcag 4320
caaaagttcg atttattcaa caaagccgcc gtcccgtcaa gtcagcgtaa tgctctgcca 4380
gtgttacaac caattaacca attctgatta gaaaaactca tcgagcatca aatgaaactg 4440
caatttattc atatcaggat tatcaatacc atatttttga aaaagccgtt tctgtaatga 4500
aggagaaaac tcaccgaggc agttccatag gatggcaaga tcctggtatc ggtctgcgat 4560
tccgactcgt ccaacatcaa tacaacctat taatttcccc tcgtcaaaaa taaggttatc 4620
aagtgagaaa tcaccatgag tgacgactga atccggtgag aatggcaaaa gcttatgcat 4680
ttctttccag acttgttcaa caggccagcc attacgctcg tcatcaaaat cactcgcatc 4740
aaccaaaccg ttattcattc gtgattgcgc ctgagcgaga cgaaatacgc gatcgctgtt 4800
aaaaggacaa ttacaaacag gaatcgaatg caaccggcgc aggaacactg ccagcgcatc 4860
aacaatattt tcacctgaat caggatattc ttctaatacc tggaatgctg ttttcccggg 4920
gatcgcagtg gtgagtaacc atgcatcatc aggagtacgg ataaaatgct tgatggtcgg 4980
aagaggcata aattccgtca gccagtttag tctgaccatc tcatctgtaa catcattggc 5040
aacgctacct ttgccatgtt tcagaaacaa ctctggcgca tcgggcttcc catacaatcg 5100
atagattgtc gcacctgatt gcccgacatt atcgcgagcc catttatacc catataaatc 5160
agcatccatg ttggaattta atcgcggcct cgagcaagac gtttcccgtt gaatatggct 5220
cataacaccc cttgtattac tgtttatgta agcagacagt tttattgttc atgatgatat 5280
atttttatct tgtgcaatgt aacatcagag attttgagac acaacgtggc tttccccccc 5340
cccccattat tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg 5400
tatttagaaa aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga 5460
cgtctaagaa accattatta tcatgacatt aacctataaa aataggcgta tcacgaggcc 5520
ctttcgtc 5528
<210> 393
<211> 594
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(594)
<400> 393
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac ggg tca ggc 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Gly Ser Gly
50 55 60
tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat gag 240
Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu
65 70 75 80
cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca atc 288
Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala Ile
85 90 95
aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc agc 336
Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser
100 105 110
gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg aac 384
Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn
115 120 125
cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat gag 432
Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu
130 135 140
aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat gga 480
Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly
145 150 155 160
tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct gtg 528
Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser Val
165 170 175
aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag ctg 576
Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu
180 185 190
aat cga gag aaa att gac 594
Asn Arg Glu Lys Ile Asp
195
<210> 394
<211> 198
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 394
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Gly Ser Gly
50 55 60
Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu
65 70 75 80
Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala Ile
85 90 95
Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser
100 105 110
Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn
115 120 125
Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu
130 135 140
Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly
145 150 155 160
Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser Val
165 170 175
Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu
180 185 190
Asn Arg Glu Lys Ile Asp
195
<210> 395
<211> 594
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 395
gtcaattttc tctcgattca gcttactctc ttcagaatat ttgggatagt cgtaagtgcc 60
gttcttcaca gactccatac attcattgtt gcacttatgg taaaactcga agcatccatt 120
cccgatttct ttggcattgt tcttcagctg ggatttgacc ttctcataca gattcttcac 180
gttgctatcg tggaacagca gagtccactg gttcagcagc agcaccagca gctcagccag 240
gtctgttccg gagcctccgc tgcccatttt ttcgatgaca gaattcacca tgttagtaat 300
gccattgatt gcgttctgtg tagacttctg atcagcggcg tagccgctgc cctgctcatt 360
ctgatggtgg tagccgtacc acccgtccac cattcctgtc cagcctgacc cgttgcgcag 420
tccggtgacc atcctcagtc cgctgcccag attcactgag tgggtgacag tcacgttctt 480
ctccaggacg gtatccactg tgtcggtgga gttgtttgcg tgatagccga tgcagatagt 540
gtcagcgtag gttgcggtaa aagtacacag caggaccagc agtttggcct tcat 594
<210> 396
<211> 1104
<212> DNA
<213> 人工序列
<220>
<223> 合成
<220>
<221> CDS
<222> (1)..(1104)
<400> 396
atg aag gcc aaa ctg ctg gtc ctg ctg tgt act ttt acc gca acc tac 48
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
gct gac act atc tgc atc ggc tat cac gca aac aac tcc acc gac aca 96
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
gtg gat acc gtc ctg gag aag aac gtg act gtc acc cac tca gtg aat 144
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
ctg ggc agc gga ctg agg atg gtc acc gga ctg cgc aac ggg tca ggc 192
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Gly Ser Gly
50 55 60
tgg aca gga atg gtg gac ggg tgg tac ggc tac cac cat cag aat gag 240
Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu
65 70 75 80
cag ggc agc ggc tac gcc gct gat cag aag tct aca cag aac gca atc 288
Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala Ile
85 90 95
aat ggc att act aac atg gtg aat tct gtc atc gaa aaa atg ggc agc 336
Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser
100 105 110
gga ggc tcc gga aca gac ctg gct gag ctg ctg gtg ctg ctg ctg aac 384
Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn
115 120 125
cag tgg act ctg ctg ttc cac gat agc aac gtg aag aat ctg tat gag 432
Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu
130 135 140
aag gtc aaa tcc cag ctg aag aac aat gcc aaa gaa atc ggg aat gga 480
Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly
145 150 155 160
tgc ttc gag ttt tac cat aag tgc aac aat gaa tgt atg gag tct gtg 528
Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser Val
165 170 175
aag aac ggc act tac gac tat ccc aaa tat tct gaa gag agt aag ctg 576
Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu
180 185 190
aat cga gag aaa att gac agt ggg ggc gac atc atc aag ctg ctg aac 624
Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu Asn
195 200 205
gaa cag gtg aac aag gag atg cag agc tcc aac ctg tac atg agt atg 672
Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser Met
210 215 220
tct agt tgg tgt tat aca cac tca ctg gac ggc gct ggg ctg ttc ctg 720
Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe Leu
225 230 235 240
ttt gat cac gca gcc gag gaa tac gaa cat gca aag aaa ctg atc att 768
Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile Ile
245 250 255
ttc ctg aat gag aac aat gtg ccc gtc cag ctg act tca atc agc gcc 816
Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser Ala
260 265 270
cct gaa cat aag ttc gag ggc ctg acc cag atc ttt cag aaa gct tac 864
Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala Tyr
275 280 285
gaa cac gag cag cat att tcc gaa tct atc aac aat att gtg gac cac 912
Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp His
290 295 300
gcc att aag agc aaa gat cat gct acc ttc aac ttt ctg cag tgg tac 960
Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp Tyr
305 310 315 320
gtg gcc gag cag cac gag gag gag gtc ctg ttt aag gac atc ctg gat 1008
Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu Asp
325 330 335
aaa atc gaa ctg att gga aac gag aat cat ggc ctg tac ctg gca gat 1056
Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala Asp
340 345 350
cag tat gtg aag ggc att gcc aag tcc aga aaa agt ggg tca tga tga 1104
Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
355 360 365
<210> 397
<211> 366
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 397
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Gly Ser Gly
50 55 60
Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu
65 70 75 80
Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala Ile
85 90 95
Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser
100 105 110
Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn
115 120 125
Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu
130 135 140
Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly
145 150 155 160
Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser Val
165 170 175
Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu
180 185 190
Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu Asn
195 200 205
Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser Met
210 215 220
Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe Leu
225 230 235 240
Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile Ile
245 250 255
Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser Ala
260 265 270
Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala Tyr
275 280 285
Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp His
290 295 300
Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp Tyr
305 310 315 320
Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu Asp
325 330 335
Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala Asp
340 345 350
Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
355 360 365
<210> 398
<211> 1104
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 398
tcatcatgac ccactttttc tggacttggc aatgcccttc acatactgat ctgccaggta 60
caggccatga ttctcgtttc caatcagttc gattttatcc aggatgtcct taaacaggac 120
ctcctcctcg tgctgctcgg ccacgtacca ctgcagaaag ttgaaggtag catgatcttt 180
gctcttaatg gcgtggtcca caatattgtt gatagattcg gaaatatgct gctcgtgttc 240
gtaagctttc tgaaagatct gggtcaggcc ctcgaactta tgttcagggg cgctgattga 300
agtcagctgg acgggcacat tgttctcatt caggaaaatg atcagtttct ttgcatgttc 360
gtattcctcg gctgcgtgat caaacaggaa cagcccagcg ccgtccagtg agtgtgtata 420
acaccaacta gacatactca tgtacaggtt ggagctctgc atctccttgt tcacctgttc 480
gttcagcagc ttgatgatgt cgcccccact gtcaattttc tctcgattca gcttactctc 540
ttcagaatat ttgggatagt cgtaagtgcc gttcttcaca gactccatac attcattgtt 600
gcacttatgg taaaactcga agcatccatt cccgatttct ttggcattgt tcttcagctg 660
ggatttgacc ttctcataca gattcttcac gttgctatcg tggaacagca gagtccactg 720
gttcagcagc agcaccagca gctcagccag gtctgttccg gagcctccgc tgcccatttt 780
ttcgatgaca gaattcacca tgttagtaat gccattgatt gcgttctgtg tagacttctg 840
atcagcggcg tagccgctgc cctgctcatt ctgatggtgg tagccgtacc acccgtccac 900
cattcctgtc cagcctgacc cgttgcgcag tccggtgacc atcctcagtc cgctgcccag 960
attcactgag tgggtgacag tcacgttctt ctccaggacg gtatccactg tgtcggtgga 1020
gttgtttgcg tgatagccga tgcagatagt gtcagcgtag gttgcggtaa aagtacacag 1080
caggaccagc agtttggcct tcat 1104
<210> 399
<211> 5528
<212> DNA
<213> 人工序列
<220>
<223> 合成
<400> 399
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcagattgg 240
ctattggcca ttgcatacgt tgtatccata tcataatatg tacatttata ttggctcatg 300
tccaacatta ccgccatgtt gacattgatt attgactagt tattaatagt aatcaattac 360
ggggtcatta gttcatagcc catatatgga gttccgcgtt acataactta cggtaaatgg 420
cccgcctggc tgaccgccca acgacccccg cccattgacg tcaataatga cgtatgttcc 480
catagtaacg ccaataggga ctttccattg acgtcaatgg gtggagtatt tacggtaaac 540
tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa 600
tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac 660
ttggcagtac atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta 720
catcaatggg cgtggatagc ggtttgactc acggggattt ccaagtctcc accccattga 780
cgtcaatggg agtttgtttt ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa 840
ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg tgggaggtct atataagcag 900
agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt ttgacctcca 960
tagaagacac cgggaccgat ccagcctcca tcggctcgca tctctccttc acgcgcccgc 1020
cgccctacct gaggccgcca tccacgccgg ttgagtcgcg ttctgccgcc tcccgcctgt 1080
ggtgcctcct gaactgcgtc cgccgtctag gtaagtttaa agctcaggtc gagaccgggc 1140
ctttgtccgg cgctcccttg gagcctacct agactcagcc ggctctccac gctttgcctg 1200
accctgcttg ctcaactcta gttaacggtg gagggcagtg tagtctgagc agtactcgtt 1260
gctgccgcgc gcgccaccag acataatagc tgacagacta acagactgtt cctttccatg 1320
ggtcttttct gcagtcaccg tcgtcgacac gtgtgatcag atatcgcggc cgctctagag 1380
atatcgccac catgaaggcc aaactgctgg tcctgctgtg tacttttacc gcaacctacg 1440
ctgacactat ctgcatcggc tatcacgcaa acaactccac cgacacagtg gataccgtcc 1500
tggagaagaa cgtgactgtc acccactcag tgaatctggg cagcggactg aggatggtca 1560
ccggactgcg caacgggtca ggctggacag gaatggtgga cgggtggtac ggctaccacc 1620
atcagaatga gcagggcagc ggctacgccg ctgatcagaa gtctacacag aacgcaatca 1680
atggcattac taacatggtg aattctgtca tcgaaaaaat gggcagcgga ggctccggaa 1740
cagacctggc tgagctgctg gtgctgctgc tgaaccagtg gactctgctg ttccacgata 1800
gcaacgtgaa gaatctgtat gagaaggtca aatcccagct gaagaacaat gccaaagaaa 1860
tcgggaatgg atgcttcgag ttttaccata agtgcaacaa tgaatgtatg gagtctgtga 1920
agaacggcac ttacgactat cccaaatatt ctgaagagag taagctgaat cgagagaaaa 1980
ttgacagtgg gggcgacatc atcaagctgc tgaacgaaca ggtgaacaag gagatgcaga 2040
gctccaacct gtacatgagt atgtctagtt ggtgttatac acactcactg gacggcgctg 2100
ggctgttcct gtttgatcac gcagccgagg aatacgaaca tgcaaagaaa ctgatcattt 2160
tcctgaatga gaacaatgtg cccgtccagc tgacttcaat cagcgcccct gaacataagt 2220
tcgagggcct gacccagatc tttcagaaag cttacgaaca cgagcagcat atttccgaat 2280
ctatcaacaa tattgtggac cacgccatta agagcaaaga tcatgctacc ttcaactttc 2340
tgcagtggta cgtggccgag cagcacgagg aggaggtcct gtttaaggac atcctggata 2400
aaatcgaact gattggaaac gagaatcatg gcctgtacct ggcagatcag tatgtgaagg 2460
gcattgccaa gtccagaaaa agtgggtcat gatgaacacg tgggatccag atctgctgtg 2520
ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt gaccctggaa 2580
ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca ttgtctgagt 2640
aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga ggattgggaa 2700
gacaatagca ggcatgctgg ggatgcggtg ggctctatgg gtacccaggt gctgaagaat 2760
tgacccggtt cctcctgggc cagaaagaag caggcacatc cccttctctg tgacacaccc 2820
tgtccacgcc cctggttctt agttccagcc ccactcatag gacactcata gctcaggagg 2880
gctccgcctt caatcccacc cgctaaagta cttggagcgg tctctccctc cctcatcagc 2940
ccaccaaacc aaacctagcc tccaagagtg ggaagaaatt aaagcaagat aggctattaa 3000
gtgcagaggg agagaaaatg cctccaacat gtgaggaagt aatgagagaa atcatagaat 3060
tttaaggcca tgatttaagg ccatcatggc cttaatcttc cgcttcctcg ctcactgact 3120
cgctgcgctc ggtcgttcgg ctgcggcgag cggtatcagc tcactcaaag gcggtaatac 3180
ggttatccac agaatcaggg gataacgcag gaaagaacat gtgagcaaaa ggccagcaaa 3240
aggccaggaa ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc cgcccccctg 3300
acgagcatca caaaaatcga cgctcaagtc agaggtggcg aaacccgaca ggactataaa 3360
gataccaggc gtttccccct ggaagctccc tcgtgcgctc tcctgttccg accctgccgc 3420
ttaccggata cctgtccgcc tttctccctt cgggaagcgt ggcgctttct catagctcac 3480
gctgtaggta tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac 3540
cccccgttca gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag tccaacccgg 3600
taagacacga cttatcgcca ctggcagcag ccactggtaa caggattagc agagcgaggt 3660
atgtaggcgg tgctacagag ttcttgaagt ggtggcctaa ctacggctac actagaagaa 3720
cagtatttgg tatctgcgct ctgctgaagc cagttacctt cggaaaaaga gttggtagct 3780
cttgatccgg caaacaaacc accgctggta gcggtggttt ttttgtttgc aagcagcaga 3840
ttacgcgcag aaaaaaagga tctcaagaag atcctttgat cttttctacg gggtctgacg 3900
ctcagtggaa cgaaaactca cgttaaggga ttttggtcat gagattatca aaaaggatct 3960
tcacctagat ccttttaaat taaaaatgaa gttttaaatc aatctaaagt atatatgagt 4020
aaacttggtc tgacagttac caatgcttaa tcagtgaggc acctatctca gcgatctgtc 4080
tatttcgttc atccatagtt gcctgactcg gggggggggg gcgctgaggt ctgcctcgtg 4140
aagaaggtgt tgctgactca taccaggcct gaatcgcccc atcatccagc cagaaagtga 4200
gggagccacg gttgatgaga gctttgttgt aggtggacca gttggtgatt ttgaactttt 4260
gctttgccac ggaacggtct gcgttgtcgg gaagatgcgt gatctgatcc ttcaactcag 4320
caaaagttcg atttattcaa caaagccgcc gtcccgtcaa gtcagcgtaa tgctctgcca 4380
gtgttacaac caattaacca attctgatta gaaaaactca tcgagcatca aatgaaactg 4440
caatttattc atatcaggat tatcaatacc atatttttga aaaagccgtt tctgtaatga 4500
aggagaaaac tcaccgaggc agttccatag gatggcaaga tcctggtatc ggtctgcgat 4560
tccgactcgt ccaacatcaa tacaacctat taatttcccc tcgtcaaaaa taaggttatc 4620
aagtgagaaa tcaccatgag tgacgactga atccggtgag aatggcaaaa gcttatgcat 4680
ttctttccag acttgttcaa caggccagcc attacgctcg tcatcaaaat cactcgcatc 4740
aaccaaaccg ttattcattc gtgattgcgc ctgagcgaga cgaaatacgc gatcgctgtt 4800
aaaaggacaa ttacaaacag gaatcgaatg caaccggcgc aggaacactg ccagcgcatc 4860
aacaatattt tcacctgaat caggatattc ttctaatacc tggaatgctg ttttcccggg 4920
gatcgcagtg gtgagtaacc atgcatcatc aggagtacgg ataaaatgct tgatggtcgg 4980
aagaggcata aattccgtca gccagtttag tctgaccatc tcatctgtaa catcattggc 5040
aacgctacct ttgccatgtt tcagaaacaa ctctggcgca tcgggcttcc catacaatcg 5100
atagattgtc gcacctgatt gcccgacatt atcgcgagcc catttatacc catataaatc 5160
agcatccatg ttggaattta atcgcggcct cgagcaagac gtttcccgtt gaatatggct 5220
cataacaccc cttgtattac tgtttatgta agcagacagt tttattgttc atgatgatat 5280
atttttatct tgtgcaatgt aacatcagag attttgagac acaacgtggc tttccccccc 5340
cccccattat tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg 5400
tatttagaaa aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga 5460
cgtctaagaa accattatta tcatgacatt aacctataaa aataggcgta tcacgaggcc 5520
ctttcgtc 5528
<210> 400
<211> 198
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 400
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Gly Ser Gly
50 55 60
Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu
65 70 75 80
Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala Ile
85 90 95
Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser
100 105 110
Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn
115 120 125
Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu
130 135 140
Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly
145 150 155 160
Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser Val
165 170 175
Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu
180 185 190
Asn Arg Glu Lys Ile Asp
195
<210> 401
<211> 366
<212> PRT
<213> 人工序列
<220>
<223> 合成
<400> 401
Met Lys Ala Lys Leu Leu Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Gly Ser Gly Leu Arg Met Val Thr Gly Leu Arg Asn Gly Ser Gly
50 55 60
Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His His Gln Asn Glu
65 70 75 80
Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr Gln Asn Ala Ile
85 90 95
Asn Gly Ile Thr Asn Met Val Asn Ser Val Ile Glu Lys Met Gly Ser
100 105 110
Gly Gly Ser Gly Thr Asp Leu Ala Glu Leu Leu Val Leu Leu Leu Asn
115 120 125
Gln Trp Thr Leu Leu Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu
130 135 140
Lys Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly
145 150 155 160
Cys Phe Glu Phe Tyr His Lys Cys Asn Asn Glu Cys Met Glu Ser Val
165 170 175
Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu
180 185 190
Asn Arg Glu Lys Ile Asp Ser Gly Gly Asp Ile Ile Lys Leu Leu Asn
195 200 205
Glu Gln Val Asn Lys Glu Met Gln Ser Ser Asn Leu Tyr Met Ser Met
210 215 220
Ser Ser Trp Cys Tyr Thr His Ser Leu Asp Gly Ala Gly Leu Phe Leu
225 230 235 240
Phe Asp His Ala Ala Glu Glu Tyr Glu His Ala Lys Lys Leu Ile Ile
245 250 255
Phe Leu Asn Glu Asn Asn Val Pro Val Gln Leu Thr Ser Ile Ser Ala
260 265 270
Pro Glu His Lys Phe Glu Gly Leu Thr Gln Ile Phe Gln Lys Ala Tyr
275 280 285
Glu His Glu Gln His Ile Ser Glu Ser Ile Asn Asn Ile Val Asp His
290 295 300
Ala Ile Lys Ser Lys Asp His Ala Thr Phe Asn Phe Leu Gln Trp Tyr
305 310 315 320
Val Ala Glu Gln His Glu Glu Glu Val Leu Phe Lys Asp Ile Leu Asp
325 330 335
Lys Ile Glu Leu Ile Gly Asn Glu Asn His Gly Leu Tyr Leu Ala Asp
340 345 350
Gln Tyr Val Lys Gly Ile Ala Lys Ser Arg Lys Ser Gly Ser
355 360 365

Claims (44)

1.蛋白质构建体，其包含来自流感病毒血凝素(HA)蛋白的茎区的第一氨基酸序列和来自流感病毒血凝素(HA)蛋白的茎区的第二氨基酸序列，所述第一和第二氨基酸序列通过接头序列共价连接，
其中所述第一氨基酸序列包含来自头部区序列的氨基端末端上游的氨基酸序列的至少20个连续氨基酸残基，且
其中所述第二氨基酸序列包含来自头部区序列的羧基端末端下游的氨基酸序列的至少20个连续氨基酸残基。
2.权利要求1的蛋白质构建体，其中所述接头序列包含来自流感HA蛋白的所述头部区的少于5个连续氨基酸。
3.权利要求1的蛋白质构建体，其中所述接头序列的长度小于5个氨基酸。
4.权利要求1的蛋白质构建体，其中所述第一氨基酸序列来自选自下组的病毒的流感HA蛋白：A/新喀里多尼亚/20/1999(1999NC，H1)，A/加利福尼亚/04/2009(2009CA，H1)，A/新加坡/1/1957(1957Sing，H2)，A/香港/1/1968(1968HK，H3)，A/布里斯班/10/2007(2007Bris，H3)，A/印度尼西亚/05/2005(2005Indo，H5)，B/佛罗里达/4/2006(2006Flo，B)，A/珀斯/16/2009(2009Per，H3)，A/布里斯班/59/2007(2007Bris，H1)，B/布里斯班/60/2008(2008Bris，B)。
5.权利要求1的蛋白质构建体，其中所述第一氨基酸序列包含与来自选自下组的序列的至少40个连续氨基酸残基至少80％相同的序列：SEQ ID NO:20，SEQ ID NO:35，SEQ IDNO:50和SEQ ID NO:65。
6.权利要求1的蛋白质构建体，其中所述第一氨基酸序列包含与选自下组的序列至少80％相同的序列：SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65。
7.权利要求1的蛋白质构建体，其中所述第一氨基酸序列包含选自下组的序列：SEQ IDNO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65。
8.权利要求1的蛋白质构建体，其中所述第二氨基酸序列来自选自下组的病毒的流感HA蛋白：A/新喀里多尼亚/20/1999(1999NC，H1)，A/加利福尼亚/04/2009(2009CA，H1)，A/新加坡/1/1957(1957Sing，H2)，A/香港/1/1968(1968HK，H3)，A/布里斯班/10/2007(2007Bris，H3)，A/印度尼西亚/05/2005(2005Indo，H5)，B/佛罗里达/4/2006(2006Flo，B)，A/珀斯/16/2009(2009Per，H3)，A/布里斯班/59/2007(2007Bris，H1)，B/布里斯班/60/2008(2008Bris，B)。
9.权利要求1的蛋白质构建体，其中所述第二氨基酸序列包含与来自选自下组的序列的至少40个连续氨基酸残基至少80％相同的序列：SEQ ID NO:23，SEQ ID NO:26，SEQ IDNO:29，SEQ ID NO:32，SEQ ID NO:38，SEQ ID NO:41，SEQ ID NO:44，SEQ ID NO:47，SEQ IDNO:53，SEQ ID NO:56，SEQ ID NO:59，SEQ ID NO:62，SEQ ID NO:68，SEQ ID NO:71，SEQ IDNO:74和SEQ ID NO:77。
10.权利要求1的蛋白质构建体，其中所述第二氨基酸序列包含与选自的序列至少80％相同的序列：SEQ ID NO:23，SEQ ID NO:26，SEQ ID NO:29，SEQ ID NO:32，SEQ ID NO:38，SEQ ID NO:41，SEQ ID NO:44，SEQ ID NO:47，SEQ ID NO:53，SEQ ID NO:56，SEQ ID NO:59，SEQ ID NO:62，SEQ ID NO:68，SEQ ID NO:71，SEQ ID NO:74和SEQ ID NO:77。
11.权利要求1的蛋白质构建体，其中所述第二氨基酸序列包含选自下组的序列：SEQID NO:23，SEQ ID NO:26，SEQ ID NO:29，SEQ ID NO:32，SEQ ID NO:38，SEQ ID NO:41，SEQID NO:44，SEQ ID NO:47，SEQ ID NO:53，SEQ ID NO:56，SEQ ID NO:59，SEQ ID NO:62，SEQID NO:68，SEQ ID NO:71，SEQ ID NO:74和SEQ ID NO:77。
12.权利要求1的蛋白质构建体，其中所述第一或第二氨基酸序列连接到允许所述蛋白质构建体形成纳米颗粒的单体亚基蛋白。
13.蛋白质构建体，其包含来自流感病毒血凝素(HA)蛋白的茎区的第一氨基酸序列和来自流感病毒血凝素(HA)蛋白的茎区的第二氨基酸序列，所述第一和第二氨基酸序列通过接头序列共价连接，
其中所述第一氨基酸序列包含来自所述头部区序列的氨基端末端上游的氨基酸序列的至少20个连续氨基酸残基，
其中所述第二氨基酸序列包含来自所述头部区序列的羧基端末端下游的氨基酸序列的至少60个连续氨基酸，
其中所述60个连续氨基酸包含对应于来自H1N1NC的SEQ ID NO:149或SEQ ID NO:150的序列的多肽序列，且
其中对应于149的K1或SEQ ID NO:150的K1的所述多肽序列中的氨基酸残基被取代为除赖氨酸之外的氨基酸，并且对应于SEQ ID NO:149的E53或SEQ ID NO:50的E20的氨基酸残基被取代为除了谷氨酸之外的氨基酸残基取代，使得取代的氨基酸残基之间的相互作用的强度大于野生型蛋白质中的相互作用的强度。
14.权利要求13的蛋白质构建体，其中所述接头序列包含来自流感HA蛋白的所述头部区的少于5个连续氨基酸。
15.权利要求13的蛋白质构建体，其中所述接头序列的长度小于5个氨基酸。
16.权利要求13的蛋白质构建体，其中所述第一或第二氨基酸序列连接到单体亚基。
17.权利要求13的蛋白质构建体，其中所述第一氨基酸序列来自选自下组的病毒的流感HA蛋白：A/新喀里多尼亚/20/1999(1999NC，H1)，A/加利福尼亚/04/2009(2009CA，H1)，A/新加坡/1/1957(1957Sing，H2)，A/香港/1/1968(1968HK，H3)，A/布里斯班/10/2007(2007Bris，H3)，A/印度尼西亚/05/2005(2005Indo，H5)，B/佛罗里达/4/2006(2006Flo，B)，A/珀斯/16/2009(2009Per，H3)，A/布里斯班/59/2007(2007ris，H1)，B/布里斯班/60/2008(2008Bris，B)。
18.权利要求13的蛋白质，其中所述第一氨基酸序列包含与来自选自下组的序列的至少40个连续氨基酸残基至少80％相同的序列：SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65。
19.权利要求13的蛋白质，其中所述第一氨基酸序列包含与选自下组的序列至少80％相同的序列：SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65。
20.权利要求13的蛋白质，其中所述第一氨基酸序列包含SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50和SEQ ID NO:65。
21.权利要求13的蛋白质构建体，其中所述第二氨基酸序列来自选自下组的病毒的流感HA蛋白：A/新喀里多尼亚/20/1999(1999NC，H1)，A/加利福尼亚/04/2009(2009CA，H1)，A/新加坡/1/1957(1957Sing，H2)，A/香港/1/1968(1968HK，H3)，A/布里斯班/10/2007(2007Bris，H3)，A/印度尼西亚/05/2005(2005Indo，H5)，B/佛罗里达/4/2006(2006Flo，B)，A/珀斯/16/2009(2009Per，H3)，A/布里斯班/59/2007(2007Bris，H1)，B/布里斯班/60/2008(2008Bris，B)。
22.权利要求13的蛋白质，其中所述第二氨基酸序列包含与来自选自下组的序列的至少60个连续氨基酸残基至少80％相同的序列：SEQ ID NO:23，SEQ ID NO:26，SEQ ID NO:29，SEQ ID NO:32，SEQ ID NO:38，SEQ ID NO:41，SEQ ID NO:44，SEQ ID NO:47，SEQ IDNO:53，SEQ ID NO:56，SEQ ID NO:59，SEQ ID NO:62，SEQ ID NO:68，SEQ ID NO:71，SEQ IDNO:74和SEQ ID NO:77。
23.权利要求13的蛋白质，其中所述第二氨基酸序列包含与选自的序列至少80％相同的序列：SEQ ID NO:23，SEQ ID NO:26，SEQ ID NO:29，SEQ ID NO:32，SEQ ID NO:38，SEQID NO:41，SEQ ID NO:44，SEQ ID NO:47，SEQ ID NO:53，SEQ ID NO:56，SEQ ID NO:59，SEQID NO:62，SEQ ID NO:68，SEQ ID NO:71，SEQ ID NO:74和SEQ ID NO:77。
24.权利要求13的蛋白质，其中所述第二氨基酸序列包含选自下组的序列：SEQ ID NO:23，SEQ ID NO:26，SEQ ID NO:29，SEQ ID NO:32，SEQ ID NO:38，SEQ ID NO:41，SEQ IDNO:44，SEQ ID NO:47，SEQ ID NO:53，SEQ ID NO:56，SEQ ID NO:59，SEQ ID NO:62，SEQ IDNO:68，SEQ ID NO:71，SEQ ID NO:74和SEQ ID NO:77。
25.权利要求13的蛋白质构建体，其中所述第一或第二氨基酸序列连接到允许所述蛋白质构建体形成纳米颗粒的单体亚基蛋白。
26.包含HA蛋白和接头蛋白的蛋白质构建体，其中所述HA结构域包含流感血凝素(HA)蛋白的序列，其中所述头部区氨基酸序列的至少95％用所述接头蛋白替换，其中接头多肽的长度小于10个氨基酸。
27.权利要求26的蛋白质构建体，其中所述HA蛋白与单体亚基蛋白质连接，使得所述蛋白质构建体能够形成纳米颗粒。
28.权利要求26的蛋白质构建体，其中所述HA蛋白来自选自下组的流感病毒：A/新喀里多尼亚/20/1999(1999NC，H1)，A/加利福尼亚/04/2009(2009CA，H1)，A/新加坡/1/1957(1957Sing，H2)，A/香港/1/1968(1968HK，H3)，A/布里斯班/10/2007(2007Bris，H3)，A/印度尼西亚/05/2005(2005Indo，H5)，B/佛罗里达/4/2006(2006Flo，B)，A/珀斯/16/2009(2009Per，H3)，A/布里斯班/59/2007(2007Bris，H1)，B/布里斯班/60/2008(2008Bris，B)。
29.权利要求26的蛋白质构建体，其中所述流感HA蛋白包含来自选自下组的序列的至少50个连续氨基酸：SEQ ID NO:20，SEQ ID NO:35，SEQ ID NO:50，SEQ ID NO:6，SEQ IDNO:23，SEQ ID NO:26，SEQ ID NO:29，SEQ ID NO:32，SEQ ID NO:38，SEQ ID NO:41，SEQ IDNO:44，SEQ ID NO:47，SEQ ID NO:53，SEQ ID NO:56，SEQ ID NO:59，SEQ ID NO:62，SEQ IDNO:68，SEQ ID NO:71，SEQ ID NO:74和SEQ ID NO:77。
30.权利要求26的蛋白质构建体，其中所述流感HA蛋白具有与选自下组的HA序列至少80％相同的氨基酸序列：SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17。
31.权利要求26的蛋白质构建体，其中所述流感HA蛋白具有选自下组的氨基酸序列：SEQ ID NO:8，SEQ ID NO:11，SEQ ID NO:14和SEQ ID NO:17。
32.权利要求26的蛋白质构建体，其中所述接头多肽的长度小于5个氨基酸。
33.权利要求26的蛋白质构建体，其中所述接头多肽是三肽。
34.权利要求26的蛋白质构建体，其中所述茎区中的一个或多个氨基酸残基被突变而增加所述折叠蛋白中相邻氨基酸残基之间的疏水或氢相互作用的强度。
35.权利要求26的蛋白质构建体，其中所述接头肽是甘氨酸丝氨酸环。
36.根据权利要求12、25或27中任一项所述的蛋白质构建体，其中所述单体亚基蛋白能够装配成纳米颗粒。
37.根据权利要求12、25或27中任一项所述的蛋白质构建体，其中所述单体亚基蛋白是单体铁蛋白亚基。
38.核酸，其选自：
a)编码权利要求1-37中任一项的蛋白质的核酸分子；和
b)与(a)的核酸分子完全互补的核酸分子。
39.纳米颗粒，其包含权利要求1-37中任一项所述的蛋白质构建体。
40.权利要求39的纳米颗粒，其中所述纳米颗粒具有八面体对称。
41.权利要求39的纳米颗粒，其中所述纳米颗粒引发针对流感病毒血凝素蛋白的所述茎区的免疫应答。
42.权利要求39的纳米颗粒，其中所述纳米颗粒引发对流感毒株的免疫应答，所述流感毒株对于获得所述第一和第二氨基酸序列的流感病毒株是异源的。
43.权利要求39的纳米颗粒，其中所述纳米颗粒引发对流感毒株的免疫应答，所述流感毒株与获得所述第一和第二氨基酸序列的流感病毒是抗原趋异的。
44.权利要求39的纳米颗粒，其中所述纳米颗粒包含第二融合蛋白，其包含来自流感病毒血凝素(HA)蛋白的茎区的第三氨基酸序列和来自流感病毒血凝素(HA)蛋白的茎区的第四氨基酸序列，其中所述第三和第四氨基酸序列来自与获得所述第一和第二氨基酸序列的病毒不同的流感病毒，其中所述第三和第四氨基酸序列通过接头序列连接，以及其中所述第二融合蛋白在与单体亚基蛋白连接时能够形成三聚体。
CN201580041202.3A 2014-05-27 2015-05-27 稳定化的流感血凝素茎区三聚体及其用途 Active CN106715474B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110772479.0A CN114014937A (zh) 2014-05-27 2015-05-27 稳定化的流感血凝素茎区三聚体及其用途

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462003471P 2014-05-27 2014-05-27
US62/003,471 2014-05-27
PCT/US2015/032695 WO2015183969A1 (en) 2014-05-27 2015-05-27 Stabilized influenza hemagglutinin stem region trimers and uses thereof

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN202110772479.0A Division CN114014937A (zh) 2014-05-27 2015-05-27 稳定化的流感血凝素茎区三聚体及其用途

Publications (2)

Publication Number Publication Date
CN106715474A true CN106715474A (zh) 2017-05-24
CN106715474B CN106715474B (zh) 2021-07-27

Family

ID=53366322

Family Applications (2)

Application Number Title Priority Date Filing Date
CN202110772479.0A Pending CN114014937A (zh) 2014-05-27 2015-05-27 稳定化的流感血凝素茎区三聚体及其用途
CN201580041202.3A Active CN106715474B (zh) 2014-05-27 2015-05-27 稳定化的流感血凝素茎区三聚体及其用途

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN202110772479.0A Pending CN114014937A (zh) 2014-05-27 2015-05-27 稳定化的流感血凝素茎区三聚体及其用途

Country Status (9)

Country Link
US (4) US10363301B2 (zh)
EP (2) EP4134096A1 (zh)
CN (2) CN114014937A (zh)
CA (1) CA2950085A1 (zh)
DK (1) DK3148578T3 (zh)
ES (1) ES2924721T3 (zh)
PL (1) PL3148578T3 (zh)
PT (1) PT3148578T (zh)
WO (1) WO2015183969A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113423718A (zh) * 2019-02-08 2021-09-21 美国政府(由卫生和人类服务部的部长所代表) 基于纳米颗粒的流感病毒疫苗及其用途
CN114014937A (zh) * 2014-05-27 2022-02-08 美利坚合众国, 由健康及人类服务部部长代表 稳定化的流感血凝素茎区三聚体及其用途

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107427571A (zh) 2014-12-31 2017-12-01 美利坚合众国,由健康及人类服务部部长代表 基于纳米颗粒的新型多价疫苗
US10961283B2 (en) 2016-06-27 2021-03-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Self-assembling insect ferritin nanoparticles for display of co-assembled trimeric antigens
KR20240042570A (ko) * 2016-09-02 2024-04-02 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 안정화된 그룹 2 인플루엔자 헤마글루티닌 줄기 영역 삼량체 및 그의 용도
JP2021519596A (ja) 2018-04-03 2021-08-12 サノフイＳａｎｏｆｉ フェリチンタンパク質
WO2019195284A1 (en) * 2018-04-03 2019-10-10 Sanofi Antigenic influenza-ferritin polypeptides
CA3095174A1 (en) * 2018-04-03 2019-10-10 Sanofi Antigenic ospa polypeptides
WO2019195314A2 (en) 2018-04-03 2019-10-10 Sanofi Antigenic epstein barr virus polypeptides
KR20210018206A (ko) * 2018-04-03 2021-02-17 사노피 항원성 호흡기 세포융합 바이러스 폴리펩타이드
EP4114460A4 (en) * 2020-03-06 2024-04-17 Henry M Jackson Found Advancement Military Medicine Inc VACCINES AGAINST SARS-COV-2 AND OTHER CORONAVIRUS
CN111560074B (zh) * 2020-03-20 2021-07-09 中山大学 一种基于幽门螺旋杆菌铁蛋白的新型冠状病毒s蛋白单区域亚单位纳米疫苗
KR20230021649A (ko) * 2020-04-22 2023-02-14 메디카고 인코포레이티드 시알산과의 상호작용이 감소된 변형된 인플루엔자 헤마글루티닌을 포함하는 상부구조
WO2021231729A1 (en) 2020-05-13 2021-11-18 Sanofi Adjuvanted stabilized stem hemagglutinin nanoparticles and methods of using the same to induce broadly neutralizing antibodies against influenza
WO2022200574A1 (en) 2021-03-26 2022-09-29 Glaxosmithkline Biologicals Sa Immunogenic compositions
WO2022200582A1 (en) 2021-03-26 2022-09-29 Glaxosmithkline Biologicals Sa Immunogenic compositions
CA3222568A1 (en) 2021-06-28 2023-01-05 Glaxosmithkline Biologicals Sa Novel influenza antigens
WO2023044388A1 (en) * 2021-09-16 2023-03-23 Emergent Product Development Gaithersburg Inc. Vaccine compositions
WO2023061993A1 (en) 2021-10-13 2023-04-20 Glaxosmithkline Biologicals Sa Polypeptides
CN117586425A (zh) * 2024-01-19 2024-02-23 北京安百胜生物科技有限公司 一种重组呼吸道合胞病毒颗粒抗原其制备方法和应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1149888A (zh) * 1994-01-11 1997-05-14 福拉姆斯大学生物技术研究所 流感疫苗
WO2013044203A2 (en) * 2011-09-23 2013-03-28 THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPTARTMENT OF HEALTH & HUMAN SERVICES Novel influenza hemagglutinin protein-based vaccines

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005508916A (ja) 2001-10-01 2005-04-07 アメリカ合衆国 霊長類におけるフィロウイルス感染に対する予防ワクチンの開発
WO2003094849A2 (en) 2002-05-10 2003-11-20 New Century Pharmaceuticals, Inc. Ferritin fusion proteins for use in vaccines and other applications
US7897408B2 (en) 2005-09-12 2011-03-01 Japan Science And Technology Agency Method for producing CdS-apoferritin and ZnS-apoferritin complexes
JP5382489B2 (ja) 2008-03-29 2014-01-08 国立大学法人 奈良先端科学技術大学院大学 円偏光発光性ナノ微粒子
WO2010036948A2 (en) 2008-09-26 2010-04-01 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Dna prime/inactivated vaccine boost immunization to influenza virus
DK3148578T3 (da) * 2014-05-27 2022-08-01 Us Health Stabiliserede influenza-hæmagglutininstammeområdetrimerer og anvendelser deraf

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1149888A (zh) * 1994-01-11 1997-05-14 福拉姆斯大学生物技术研究所 流感疫苗
WO2013044203A2 (en) * 2011-09-23 2013-03-28 THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPTARTMENT OF HEALTH & HUMAN SERVICES Novel influenza hemagglutinin protein-based vaccines

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
FLORIAN KRAMMER,ET AL.: "Influenza virus hemagglutinin stalk-based antibodies and vaccines", 《CURRENT OPINION IN VIROLOGY》 *
杨文等: "基于血凝素关键序列的流感病毒疫苗", 《生命科学研究》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114014937A (zh) * 2014-05-27 2022-02-08 美利坚合众国, 由健康及人类服务部部长代表 稳定化的流感血凝素茎区三聚体及其用途
CN113423718A (zh) * 2019-02-08 2021-09-21 美国政府(由卫生和人类服务部的部长所代表) 基于纳米颗粒的流感病毒疫苗及其用途

Also Published As

Publication number Publication date
DK3148578T3 (da) 2022-08-01
US11679151B2 (en) 2023-06-20
PT3148578T (pt) 2022-08-23
PL3148578T3 (pl) 2022-10-17
EP3148578B1 (en) 2022-07-06
US20170202946A1 (en) 2017-07-20
US10363301B2 (en) 2019-07-30
ES2924721T3 (es) 2022-10-10
US20230330210A1 (en) 2023-10-19
WO2015183969A1 (en) 2015-12-03
CN106715474B (zh) 2021-07-27
US11147867B2 (en) 2021-10-19
US20190314490A1 (en) 2019-10-17
US20220031834A1 (en) 2022-02-03
EP4134096A1 (en) 2023-02-15
CN114014937A (zh) 2022-02-08
CA2950085A1 (en) 2015-12-03
US11969466B2 (en) 2024-04-30
EP3148578A1 (en) 2017-04-05

Similar Documents

Publication Publication Date Title
CN106715474A (zh) 稳定化的流感血凝素茎区三聚体及其用途
AU2016207099C1 (en) Virus-like particle with efficient epitope display
US6534312B1 (en) Vaccines comprising synthetic genes
AU728422B2 (en) Vaccines comprising synthetic genes
CZ290315B6 (cs) Konstrukty DNA, jejich pouľití a polynukleotidová vakcína
CN107106689A (zh) 用于治疗帕金森病的aadc多核苷酸
CZ259096A3 (en) Polynucleotide, method of provoking immune response and vaccine
AU3567797A (en) Hiv envelope polypeptides and vaccine
CN108884149A (zh) Hiv-1 gp41中和抗体及其用途
KR102416194B1 (ko) 재조합 이스파한 바이러스 벡터
CA3005474A1 (en) Compositions and methods for correction of heritable ocular disease
ES2854726T3 (es) Partícula similar a virus con presentación eficiente de epítopos
US20230174588A1 (en) A vaccine against sars-cov-2 and preparation thereof
Pastori et al. Induction of HIV-blocking anti-CCR5 IgA in Peyers's patches without histopathological alterations
US20140234360A1 (en) Influenza vaccine
KR20010085326A (ko) 바이러스 질환의 예방과 치료
CN1312171C (zh) 可编码hiv辅助蛋白的dna疫苗
CN101022834A (zh) 通过破坏病毒衣壳－间隔肽1蛋白的加工而抑制hiv－1复制
WO2022251208A1 (en) Compositions and methods for improved treatment of x-linked myotubular myopathy
CN105968211A (zh) 一种重组抗病毒蛋白及其制备方法和应用
WO2005070459A1 (ja) 繰返し投与を伴うベクターの発現を継続させる方法
Kirschstein l. The Virus and Poliomyelitis Vaccine
KR20060059257A (ko) 도파민 수용체를 사용한 근육 질량 또는 기능의 조절을위한 화합물의 동정 방법

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant