游动放线菌雷帕霉素生物合成基因及其分离方法和应用的制作方法

专利名称：游动放线菌雷帕霉素生物合成基因及其分离方法和应用的制作方法
技术领域：
本发明涉及基因工程领域，尤其涉及来自游动放线菌的雷帕霉素生物合成基因及其分离方法和应用。
背景技术：
免疫抑制剂的发展大大提高器官移植的成功率，在上个世纪60年代Murray等 人将硫唑嘌呤(Azathioprine，Aza)应用于器官移植，在肾移植中取得一系列的成功。为 此，硫唑嘌呤和泼尼松(Prednisone，PRD)成为第一代免疫抑制剂。由于选择性差、毒副 作用大等缺点，影响器官移植的成功率。1976年微生物来源的免疫抑制剂一一环孢菌素 A (Cyclosporin, CSA)被发现，并于1978年成功地应用于器官移植，开辟了器官移植的新纪 元，大大降低免疫抑制剂的毒副作用，成为选择性佳的免疫抑制剂药物。环孢菌素A也成为 第二代免疫抑制剂的代表。伴随着从微生物代谢产物中寻找新型免疫抑制剂的热潮，第三 代免疫抑制剂如n(-506、麦考酚酸酯(Mycophenolate)和雷帕霉素(Rapamycin)等应运而 生，使得器官移植再次出现新的飞跃。目前，第三代免疫抑制剂已经成为临床器官移植的主 要药物，在免疫抑制效率、选择性等方面大大优于第二代。雷帕霉素本身在临床应用效果良 好，成为生物利用度更好的免疫抑制剂药物。另外，雷帕霉素具有多种生物活性如抗真菌、 抗肿瘤、抗病毒等活性，其新的适应症开发正在进行中。鉴于雷帕霉素良好的临床效果，其生物合成途径也成为科学家研究的热点。自 1995年获得吸水链霉菌雷帕霉素生物合成基因簇以来，各国科学家针对该基因簇中的聚酮 合成基因和后修饰基因进行了大量的研究。而对于1995年发现的另一株雷帕霉素高产菌 游动放线菌的雷帕霉素生物合成基因簇的研究未见报道。因此本领域迫切需要了解来自游动放线菌的功能未知的基因及其应用。

发明内容
本发明旨在提供一种新的来自游动放线菌的雷帕霉素生物合成基因。本发明的另一个目的是提供上述基因的应用。在本发明的第一方面，提供了一种如SEQ ID NO 1的核苷酸序列。本发明还提供了一种如SEQ ID NO 1的核苷酸序列的功能变异体。本发明提供了一种含有如SEQ ID NO 1或其功能变异体的载体。本发明提供了一种用含有如SEQ ID NO 1或其功能变异体的载体转化的微生物。本发明一种如SEQ ID NO 1的核苷酸序列编码的氨基酸序列；较佳地，是如SEQID NO 2的氨基酸序列。本发明提供了一种如SEQ ID NO :1的核苷酸序列编码的氨基酸序列的功能变异体 或突变体；较佳地是如SEQ ID NO 2的氨基酸序列的功能变异体或突变体。本发明提供了一种含有如SEQ ID NO 1的核苷酸序列编码的氨基酸序列或其功能 变异体或突变体或其部分的蛋白质。较佳地，是如SEQ ID NO :2的氨基酸序列或其功能变异体或突变体或其部分的蛋白质。
在本发明的第二方面，提供了一种游动放线菌雷帕霉素生物合成聚酮合成酶的制 备方法，所述的方法包括步骤培养用含有如SEQ ID NO :1或其功能变异体的载体转化的 微生物，从培养基中分离游动放线菌雷帕霉素生物合成聚酮合成酶。在本发明的第三方面，提供了如SEQ ID NO 1的核苷酸序列的用途。本发明提供了如SEQ ID NO 1的核苷酸序列在鉴定游动放线菌雷帕霉素生物合成 聚酮合成酶结构基因和调节基因中的应用。本发明提供了如SEQ ID NO 1的核苷酸序列在通过增加基因剂量，或使用更有效 的启动子或通过基因操作(如对调节基因蛋白表达或调节基因识别位点的基因操作)改变 调控作用来提高游动放线菌雷帕霉素生物合成聚酮合成酶合成的产量上的应用。本发明提供了如SEQ ID NO 1的核苷酸序列在分离与游动放线菌雷帕霉素生物合 成聚酮合成酶相关的天然物质的生物合成基因中的应用。本发明提供了如SEQ ID NO 1的核苷酸序列在消除不需要的游动放线菌雷帕霉素 生物合成聚酮合成酶额外组分生物合成途径中的应用。本发明提供了如SEQ ID NO 1的核苷酸序列在获得游动放线菌雷帕霉素生物合成 聚酮合成酶中的应用。本发明提供了如SEQ ID NO 1的核苷酸序列在获得雷帕霉素中的应用。本发明提供了如SEQ ID NO :1的核苷酸序列在由合成的或由微生物制备的前体合 成雷帕霉素或类似化合物中的应用。据此，本发明提供了来自游动放线菌的功能未知的基因及其应用。


图1显示了 1214bpPCR产物编码的氨基酸与已知的雷帕霉素产生菌吸水链霉菌中 聚酮合成酶保守区的同源性比较结果。图2显示了 actin-rapA蛋白的5个模块和24个结构域。
具体实施例方式发明人经过广泛而深入的研究，以分子生物学手段，在雷帕霉素产生菌游动放线 菌中以聚酮类化合物合成酶的保守序列克隆相关基因片段，并以该基因片段为探针，从雷 帕霉素产生菌游动放线菌基因组中克隆并获得雷帕霉素生物合成相关基因rapA，从而完成 了本发明，也为提高雷帕霉素发酵产量和优化改造其结构奠定了基础。利用生物软件MegAlign程序对NCBI数据库中部分I型聚酮合成酶编码序列分 析，根据其氨基酸序列的保守区设计一对简并引物上游引物5，TSAAGTCSAACATCGGBCA3，下游引物5，CGCAGGTTSCSGTACCAGTA3，其中S = G/C，B = T/G/C以游动放线菌基因组DNA为模板，在taq酶作用下进行PCR反应，结果扩增出 1214bp特异性条带。将1214bpPCR产物测序分析，结果显示，该PCR产物编码的氨基酸与已 知的雷帕霉素产生菌吸水链霉菌中聚酮合成酶保守区同源性最高，其同源性如图1所示。
1214bpPCR产物序列分析结果说明已克隆到了聚酮合成酶的部分编码基因。因此 以此PCR产物为探针，选择高严谨性的杂交条件与游动放线菌基因组文库进行菌落原位杂 交。最终从文库中获得阳性克隆。将该阳性克隆所含Fosmid质粒通过鸟枪法进行大规模 测序。测序结果通过Blast程序与NCBI数据库中序列进行同源性比较及保守序列分析，确 定了一个完整的基因阅读框序列，大小为23817bp (SEQ ID NO 1)，并证明该基因参与雷帕 霉素的生物合成，本发明中命名为actin-rapA。本发明提到的上述特征，或实施例提到的特征可以任意组合。本案说明书所揭示 的所有特征可与任何组合物形式并用，说明书中所揭示的各个特征，可以任何可提供相同、 均等或相似目的的替代性特征取代。因此除有特别说明，所揭示的特征仅为均等或相似特 征的一般性例子。本发明的主要优点在于 1、通过本发明成功地获得了游动放线菌雷帕霉素生物合成中关键的聚酮合成酶基因。2、通过对该基因的结构改造或者通过基因倍增可以提高游动放线菌雷帕霉素产 量，可以获得新的雷帕霉素衍生物。3、本发明的结果可以应用于雷帕霉素生产菌株的遗传选育，提高其发酵水平。下面将结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本 发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法，通常按照 常规条件，例如Sambrook等人，分子克隆实验室手册(New York =Cold SpringHarbor Laboratory Press, 1989)中所述的条件，或按照制造厂商所建议的条件。除非另外说明，否 则所有的百分数、比率、比例、或份数按重量计。本发明中的重量体积百分比中的单位是本领域技术人员所熟知的，例如是指在 100毫升的溶液中溶质的重量。除非另行定义，文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意 义相同。此外，任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。文 中所述的较佳实施方法与材料仅作示范之用。实施例1雷帕霉素产生菌游动放线菌总DNA的提取菌种来源游动放线菌与文献来源菌种一致Nishida，H.，T. Sakakibara, et al. (1995). “ Generation of novel rapamycin structures by microbial manipulations. " J Antibiot (Tokyo)48(7) :657_66.取少量游动放线菌菌丝体接种于含5ml YEME培养基的试管中，30°C，振荡培养约 72小时，接种5%至50ml YEME培养基中，30°C，振荡培养24小时，3500rpm离心手机菌丝 体，用裂解液洗两次，存于-20°C供提取基因组DNA用。向手机的菌丝体在中加入IOml裂 解液(含溶菌酶5mg/ml)，涡旋至均一，37°C水浴60分钟，加入0. Iml蛋白酶K (4mg/ml)， Iml 10% SDS,混勻迅速放入55°C水浴60分钟，待溶液澄清。置于冰上冷却，加入2. 5ml 5M KAc，冰上冷却15分钟。加入IOml饱和酚，混勻，IOml氯仿，混勻，12000rpm, 4°C离心20分 钟。用破口的Iml枪头将水相吸出转移至新的离心管，加等当量的氯仿抽提，12000rpm，4°C离心10分钟，用破口的Iml枪头将水相吸出转移至新的离心管，加入0. 1体积的3M NaAc, 两倍体积的无水乙醇，混勻，有絮状DNA出现。将其勾出至于新的离心管中，加入5ml 70% 的乙醇洗涤，用枪吸净液体，加入5ml TE溶解，加入32ul RNA酶(终浓度为50ul/ml)，37°C 水浴30分钟。一次用等体积的饱和酚抽提两次，氯仿抽提两次，向水相中加入加入0. 1体 积的3M NaAc，两倍体积的无水乙醇，混勻，有絮状DNA出现。将乙醇吸出，在加入Iml无水 乙醇洗涤，吸出，超净台中吹干，溶于Iml TE中。
实施例2雷帕霉素产生菌基因组文库的建立首先通过机械打断实施例1得到的游动放线菌总DNA，获得大小为20_40kb的DNA 片段，回收。将大肠杆菌EPIlOO划线于空白LB平板上37°C过夜培养。挑取EPI100单克隆 接种于3mlLB (含IOmM MgSO4)液体培养基中，37°C摇菌培养至OD6tltl = 0. 8-1. 0至于4°C备 用。将总DNA大小为20-30kb片段与fosmid载体连接过夜。从_80°C冰箱中取出包装混合 物(含包装蛋白50ul)置于干冰桶中，将包装物在直接迅速融化，在刚刚开始融化取出25ul 包装蛋白置于1. 5ml离心管中并加入6ul的连接产物，枪混勻30°C水浴90min。剩余25ul 包装蛋白放回-80°C冰箱待用。水浴结束后加入剩余25ul包装蛋白液30°C水浴90min。水 浴结束后向离心管中加入Phage Dilution Buffer 600ul，15ul氯仿，轻轻混勻，置于4°C 备用。将蛋白包装液每5ul于IOOuld大肠杆菌EPIlOO菌液混合，37°C水浴20min。水浴 后将混合液分别涂布于含12. 5ug/ml氯霉素的LB平板上，37°C培养过夜。测定噬菌斑形成 单位(pfu)以估算文库的效价。然后随机挑取3840个单克隆于10块含12. 5ug/ml氯霉素 LB培养基的384孔板中，过夜培养。容纳后加入甘油，甘油终浓度为20%，将10块384孔 板保存于_80°C。实施例3核酸分子杂交1. DIG DNA标记将待标记的DNA用无菌水稀释至总体积15ul，沸水中加热变性 10分钟，立即至于冰中冷却。接着加入2ul引物混合物，2ul dNTP混合物，Iul酶，混合均与 后，37°C水浴约16小时。加入0. 8ul 0. 8M EDTA (pH8. 0)以终止反应，加入2. 5ul4M LiCl 混合均勻，再加入75ul预冷的无水乙醇沉淀标记后的DNA，置于_80°C沉淀40分钟。4°C， 12000rpm离心20分钟收集DNA，用预冷的70%乙醇洗涤DNA沉淀，真空干燥后重新溶于 50ul TE (pH8. 0)中。2. DIG DNA探针标记后的质量检测稀释标记的DNA探针，至以下六个梯度，1、 ΙΟ—^ΙΟ—^ΙΟΛΙΟΛΙΟ—5。稀释标记的对照 DNA 至浓度 lug/ml、100ng/ml、10ng/ml、lng/ml、 100pg/mlU0pg/mL·按步骤3. 5进行显色反应，对比标记的DNA探针和DIG标记的对照DNA 的显色强度以决定标记的DNA探针浓度。3.菌落原位杂交的膜转移将保存于-80°C的基因组文库菌液混合后，取50ul，用 450ul LB稀释得到10—1的稀释倍数。倍比稀释得到10-2、10-3、10-4、10_5、10-6。300ul涂布平 板(15cmX 15cm，平板为LB/12. 5ug/ml氯霉素)。选取合适的比例，使每块平板约1200-1500 个克隆。找选定的比例均勻涂布四块平板，37°C培养过夜。根据平板大小剪取滤膜，用软铅 铅笔或圆珠笔在干滤膜上作好标记，用水浸湿后将湿滤膜夹在干的3匪滤纸之间，用铝箔 松散地包好，液相循环高温高压消毒。将干的无菌无去污剂污染的尼龙膜标记面向下铺于平板表面与菌落接触，直至滤膜完全浸湿。滤膜接触琼脂后，不要移动滤膜。滤膜一就位， 立即在平板对应位置进行标记，将滤膜和平板进行定位。用平口镊子加紧滤膜边缘，以平稳 的一次性动作将滤膜从琼脂板表面揭下。原始的平板置于培养箱中4-5小时，使克隆重新 生长作为原平板。将3MM滤纸(与滤膜形状大小一致)置于适于的平板底部，分别浸泡在 下面4种液体中10% SDS、变性液、中和液、2XSSC。倾去多余的液体，用一根IOml移液管 滚压滤纸，以出去滤纸与托盘底部的气泡。用钝口镊子揭下琼脂板上的尼龙膜，菌落面向上 至于SDS浸湿的3MM滤纸上放置3min。第一张滤膜在SDS溶液中浸泡3min后，将其转到用 变性液浸湿的第二张滤膜上，其余从琼脂版上揭下的滤膜也以同样次序进行转移，每张滤 膜都要在变性液中浸泡5min。将滤膜转到已经在中和液中浸泡的第三张3MM滤纸上，并浸 泡 5min。将滤膜转到已经在2 X SSC液中浸泡的最后一张3匪滤纸上，并浸泡5min。待滤膜晾干后，与紫外交联机上进行交联。交联后将滤膜平铺在搪瓷盒中，用吸水纸分隔开，80°C 烘烤2h。4.预杂交和杂交准备水浴锅开启调好至杂交温度，配置预杂交工作液，计算好tm值。将DIG Easy Hyb预热(37°C _42°C )，用手套封塑成合适滤膜大小的空间，每两张 滤膜放入一只手套中，标记面均朝外。加入5ml预热的杂交液，出去气泡后封口。将杂交袋 放入预热水浴锅中轻微晃动，预杂交30min。将DIG标记DNA探针煮沸5min使变性后立即 至于冰上。将变性的DIG标记DNA探针加入到预热的DIG Easy Hyb中混合均勻但避免产 生气泡。(气泡会导致背景)将杂交袋剪开小口，倒出预杂交液，加入含有探针的杂交液， 封口后放回水浴锅中，轻微摇晃过夜。用2XSSC，0. 1% SDS为洗脱液，室温2X 5min洗脱。 用0. 5XSSC，0. 1% SDS为洗脱液(预热至洗脱温度)，68°C 2X15min洗脱。5.显色反应(所有步骤均在15-25 °C下操作)在杂交和严谨洗脱之后，将滤膜置于Washing buffer中漂洗l-5min。在 IOOmlBlocking buffer中漂洗30min。用手套封塑成合适滤膜大小的空间，每两张滤膜放 入一只手套中，标记面均朝外。加入5ml Antibody solution除去气泡后封口，摇晃30min。 将滤膜置于Washing buffer中漂洗2X 15min。在20ml Detection buffer中摇晃平衡 2-5min。用手套封塑成合适滤膜大小的空间，每两张滤膜放入一只手套中，标记面均朝外。 加入5ml color substrate solution除去气泡后封口，放置于显色的避光暗盒中。在显色 过程中需静止，不能晃动。隔一段时间观察显色结果。将滤膜取出用双蒸水漂洗5min终止 显色反应。实施例4蛋白功能分析根据 ASMPKS (Analysis System for Modular Polyketide Synthesis)软件对所 获得的actin-rapA蛋白进行了结构和功能的分析，结果如下actin-rapA蛋白全长为7939个氨基酸，一共包含了 5个模块，共计24个结构域 (见图2所示)。该蛋白的功能为负责雷帕霉素合成的起始及其链的延伸。以上所述仅为本发明的较佳实施例而已，并非用以限定本发明的实质技术内容范围，本发明的实质技术内容是广义地定义于申请的权利要求范围中，任何他人完成的技术 实体或方法，若是与申请的权利要求范围所定义的完全相同，也或是一种等效的变更，均将 被视为涵盖于该权利要求范围之中。序列表 〈110〉上海医药工业研究院〈120〉游动放线菌雷帕霉素生物合成基因及其分离方法和应用<130)092092<160>7<170>PatentIn version 3.3<210>1<211>23817<212>DNA<213>Actinoplanes<400>1atgtcacgcg cggaattgat acggccgctc cacgaattgc ttcgcgtgaa tgccgggcga60cgcggcgaca aggtggccta cgcggattcc cggcggtccg tgacgcacgccgagctgctt120ctccggaccg ggcggctcgc cggtcatctg gccgggctcg gcgtcgagcg cggcgaccgg180gtggcgatcc tgctgggcaa ccgcgtcgag acgatggaga gctacctggccatcgcccgc240gccggcgcga tcgccgtgcc gctcaacacc gaggcctccg acgccgagatcgagcactgc300ctgtccgaca gcggcgccgt ggccgtcctg accggtgaag cccatctcga cctggtacgc360cgggtggccc ccgccgcggc tgccgtcccg gccggcgaca tcgacgagctggccggcacc420gaaccggtca ccccggcccg cgacgacctg aggctcgacg agccggcctg gatgctctac480acctccggca ccacgggcac ccccaagggc gtcgtgtcca cccagggcag cgggctgtgg540tcggccgcga actgcgacgt gcccgcctgg cagctgaccg aggacgacgtcctgctctgg600ccggcgccgc tgttccacag cctcgcccac cacctgtgcc tgctggccgtcaccgccgtc660ggcgcgaccg cgcggatcct cggcaccttc gtggccggcg aggtcctcga ccagttgcgc720gaacacaact gcaccgtcct cgtcggcgtc cccaccatgc accgctacctggtggccgcg780gccggtgccg gcggagcccg tacccccgcg ctcaagatgg gcctggtcgccggcgcggtc840gcacccccgg cgctcatcca gggcttcgag gacgtcttcg gggtgccgctgctcgacacg900tacggctgca ccgagaccac cggctcgctc acggtgaact ggctcgacgg tccccgggtc960cccggctcgt gcgggcttcc cgtacccggg gtggcgctgc ggttcgtcga cccggtcacc1020ggtgccgacg tacccagcgg tgccgaaggt gaactctggg cgcgcacaccgagcgtcatg1080agcggctacc acggccagcc cgacgccacc agcgaggtgc tcaccgacgg ctggtaccgc1140accggtgacc tggcccggca gagcgcgtcg ggacacgtca ccatcaccgg ccggatcaag1200gagctcatca tccgcggcgg ggagaacatc cacccccgcg agategaaacggtggcgctc1260gacgtacccg gggtcaagga cgcggccgcg gcggggcgcc ggcatcccgtcctcggcgag1320atcccggcgc tgtacgtcgt tgccgagccc ggtggcgtgg acgccgaggcggtgctcgac1380cggtgccgcg accggctgtc gtacttcaag gtcccggagg agatctacca ggtcgccgcc1440atcccccgga cggcctcggg aaaggtgcga cggaaccggc tcacccagga gccggccgaa1500
ctgctcgccg gggccgcggg caccgagtcg ctgcaccggc tcgagtggac gcccatcgac1560ctgcccgccg tcagcctcgc cgagcggccg caggacgccg cccgggtgcg caccaccagg1620cacgcggtgc acgt cacgac cggcgacctg ccggaccccg ggcaagcagc ccggtgggac1680gcctaccggg ccgaacccga cgtcgtgctc gtcgacctcg acgacaccga ccccggcgac1740gccgtcctcg cgacgctggc cggcctgggc gagccgctca tcgcgctgcg cgagggcaag1800gcgtacgtcg cgcggctcgc cgacgccgcc agccgctcgc tcaccgtgcc cgccgaccgt1860gcctgggtcc tgcgccatcc gagcagcgga accctgcgcg acctcgccct ggtcgccgat1920gacacggccg ggcgcgccct gcaacccggc gaggtgcggc tcgccgtacg cgcagccgga1980ctgaacttcc gcgacgtgct catcgcgctg ggcacctacc ccggcgaggg cgtgatgggc2040ggcgaggccg ccggcgtcgt gctcgaggtc ggccccggcg tcaccgggct gaaccccggc2100gaccgggtgt tcggcctggt caccgcggcg ttcgggccga tcgccatcac cgaccaccgg2160acgctcggcg tgatccccgc cgactggtcg ttcgcgaccg cggcctccgt gcccatcgtc2220ttcgccaccg cctactacgg cctggtggac ctcgcggcgc tcggcgcggg cgaatccgtg2280ctcatccacg cgggcgcggg cggcgtcggc atggccgcca cccagatcgc ccagcacctc2340ggcgcccgga tcttcgccac ggcaagtgcc ggcaaacatc acatcctccg tacggcgggg2400ctggccgagg accagatcgc cgactcccgt accaccggct tccagaacgt gttcccgcgc2460ggcctagacg tcgtgctgaa ctcgctcagc ggggagttcg tcgacgcctc ggtcagcctg2520ctcgccgacg gcggccgctt cctcgagatg ggcaagaccg acatccggga cgcggaccac2580gtcgtcgccg accggcccgg cgccacctac caggcgttcg acctgctgga cgcgggcccg2640gaccggctgc gcgagatcat cgccgagctg ctcgacctgt tcgcccgggg ggtgctgcgg2700ccgctgccgc tgcgcgcctg ggacatccgt caggcgcggg acgcgttcag ctggatgagc2760cgcgcccggc acatcggcaa gatggtgctg accgtcccgc acgggctcga cgccgacggc2820acggtgctga tcaccggcga ctccggattc cgcgccggcc gcgtggcccg gcatctggtg2880tcccatcacg gggttcgcca tctggtgctg gacaccggcc agccggtcga cgagacgctc2940gtcgccgagc tgaccgccct cggcgcggcg gtcaccccca ctgcgcagca tccgttgacg3000gcagtggtcc acaccggcgg ccccggcctc gctgcactcg accagcagac ccgcagcctc3060gacctcgccg cattcgtggc cttcagcgag gacgccccgg ccaccgtcga agccctcacc3120cgccgccgcc gagccgacgg cttcccggcc acggcgatcg cctggggcct gcccgagggc3180gaaccggcgg cgatccgcgg cgagctgatc ggccgtgcgc tggcggcgcc cgacccggcg3240tacgtggtca cccggatcaa caccgccggc ctgcgcgccc tggcagccgc cggggagctg3300ccgcccgtac tgcggaacct ggcagcccgc cgcgaccaac ccgggacgcg caccggtgaa3360cggacccgga ccggcctgct cgatctggtg cggcgcagca tcatcgacat cctcgggccg3420gccgccggcg agcgcttcgc tccgggccgg acgttccggg agaccggcat cgactcgctg3480accgccgtgg agctgcgcaa cagcttggca caggccaccg ggctgccgct gccggccacg3540ctggtcttcg actacccgac cccggccgtg ctggtcgcgc ggctggaaga gctgaccggc3600ggcgcgcccg gtacgtcggc accggtgtcc gccacggtcg gtcaggacga accgctggcg3660atcgtgggta tggcttgccg gttgccgggt ggggtgtcgt cgccggagga cctgtggcgg3720ctggtggagt cgggcacgga tgcgatctcg ggtttcccgg ttgatcgtgg ctgggatgta3780gacgggttgt tcgatccgga tcccgacgcg gtgggcaaga cgtattgcgt gcagggtggt3840
ttcctggacacggcggcgga gttcgacgcg gcgttcttcg ggatcagtcc ccgtgaggcc3900ctggcgatggatccgcagca gcggctggtg ctggaggctt cgtgggaagc cttcgagcgg3960gccggtatcgaacccggctc ggtacgcggc agcgacaccg gcgtgttcat gggggccttc4020gccggaggctatgcggccga cctcgaaggc ttcggtgcga cggccggtgc gacaagtgtg4080ttgtcggggcgggtgtcgta cttcttcggg ttcgagggtc cggcgatgac ggtggacacg4140gcgtgttcgtcgtcgttggt ggctttgcat caggccgggt acgcgttgcg gcagggtgaa4200tgctcactggctcttgtcgg tggtgtcacc gttatggcaa gcccgcagag ttttgtggag4260 ttctcccggcagcgggggct ggctgcggac ggtcgtagta aggcgtttgc cgatgctgcc4320gatggtacgggctgggctga gggtgtcggt gtgctgctcg tcgagcggct gtcggatgcg4380caggctcaagggcatcaggt ccttgcggtg gtacggagct ccgccgtgaa ccaggacggt4440gcctcgaacgggctgtccgc gccgaacggg ccgtcgcagc agcgggtgat ccggcaggcg4500ctggccaatgcggtgctgac tgcggcggac gtcgatgttg tggaagccca tgggacgggt4560acgacgctgggtgatccgat cgaggcgcag gcggttatcg ccacgtacgg gcaggatcgc4620tcgacgccgttgttgctggg ctcgttgaag tcgaacatcg ggcatactca ggctgccgct4680ggtgtggctggtgtgatcaa gatggtgatg gcgttgcggc acggggtggt gccgcggtcg4740cttcatgttgacgtgccgtc gcgtcatgtt gactggtcgg ctggtgctgt tgatgtggtc4800acgtcgaatcaaccgtggcc gtcgtcggat cggccggggc gtgctggtgt gtcggcgttc4860ggggtcagtggcaccaacgc gcatgtgatt ctggagagtg cgcctttcga gccggcggat4920cagattgccgggccggtgcc cgtggtggcg gacgtcgtgc cgctggtgct gtctgctcgc4980actgtgccggcgttgacgga gcttgaggcg cgggtgcgcg cctatgtgtc ggcggccgag5040gatgacagggctgttgctgc gacgttggcg tcgtctcggg cggtgttcga gcaccgggct5100gtattgatcggcgaggacac cgtcaacggg tctgcgttga gcgatccccg cattgttttc5160gtgttccccggccagggctg gcagtggctc ggcatgggcg ttgcgttgcg cgactcgtcg5220gtcgtcttcgcctcccggat ggccgagtgt gctgccgcgc tcagcgagtt cgtcgattgg5280gatctgtttgctgccctcga cgacccggct gtggttgatc gggttgatgt ggtccagccg5340gtgtgctgggcggtcatggt gtcgctggcc gcggtctggc aagccgctgg tgtcaccccc5400gacgccgttgtcgggcactc ccaaggtgag atcgccgctg cggtggtcgc ggggtcactg5460tcgttgcgcgacggcgcacg ggtagtggcg ttgcgcagcc agctgatcgc ccagggcctg5520gccggacgtggtgccatggc ctcgattgcg ctgccggctg atgagatcac cctggttgag5580ggtgcgtggatcgcggcgct caatggcccg gtttccacgg tgattgcggg cacgccggat5640gcggtcgaggcggtgcttgc cgcgcaggat gccagggtgc ggcgtatcgc ggtggattat5700gcctcgcacaccccgcaggt tgaggcgatt cgtgatgagt tgctggcgtt gaccgctgat5760gttgactcgcgggcccctgc cgtgccgtgg ttgtcaactg ttgacggcac gtgggtggat5820ggcccgctgagcgttgacta ctggttccgc aacctgcgtg agcaagtcgg ttttgctcaa5880gcggtggacgtgctcgccgg caccgggccc gcggcggtgg gcgaggcagt cttcatcgag5940gtgtcggcaagccccgtatt gatgcagtcc atggttgacg cggtcacggt gccgacgttg6000cggcgtgatgatggatcggc cactcggctg gtgacctcgc tggctgaggc gttcgtgcag6060ggtgtcgccgttgattgggc ggcagtgctc ggagctggcg ctgagcgggt gctcgacctg6120ccgacgtatccgttccagcg gcagcgtttc tgggcgctgc ccgatcgggc gagcggggac6180
gtagcgggtctgggtttgga cgcggtgcag cacccgttgc tgggtgcggt ggtggcgttg6240ccgggctccgacagtgtcgt gttgaccggc cgggtatcgc tggcgacgca cagttggctg6300gccgatcacgcggtgcgggg caccgtgttg atgccgggca ccgggtttgt tgagctggtg6360gtgcgggccgctgacgaggt cggctgcggt gttgttgacg agctggtgat tgaggcgccg6420ttgcgcttgccggtggccgg tggggtgcag ttgtcggtgc cggtggggga ggccgacgag6480ggtgggcgtaggcaggtgac ggtccactcg cgtacggatg cggctgacac ctggacccgg6540cacgtgaccggcaccgtcag cgctgccagt gccccggcaa ccacgccgga cctggccgcc6600tggccacctggccaggcgca gccggtcgac ctctccggct tctacgacga gctcgctgcg6660gtgggctacgagtacggacc cgccttccag gggctgcggg ctgcctggcg cgccggggac6720acggtgtacgcggaggtggc gctcgccgac gccctggtgc aggacgcggg ccggttcgcc6780gtacacccggctctgctgga cgccgctctg cataccggtc ttctcaccgg gccggacaac6840cggcaaggcgtccggttgcc gttctcctgg aacaacgtca gcatccacgc gagcggccca6900gctcggctccgcgtcaccat gaccggcgaa ggcctgcgcc tcgccgacga gttcggacat6960cccgtggccgagatcggcgc gctggtgacc cggccgatga ccgacgatgc cgtcaccgac7020ctgctcgccgtcacctggac cgagatcccg gccgtggcgt cggccaccgg ggccgaggtg7080ttcacggcgcttccgtccga cgccgctgcc gacgtgccgg ccgagacccg ggcgctgacc7140gtccgtaccctggcggcgat ccagtcatgg ctggatcggg atgacggcac ccttgtcatc7200aatgttgacaccgggctcac cggcgcggct gtgtcgggtc tcgtacggtc ggcgcagtcg7260gagcacccgagccggttcgt gctggtggag agcgacgacg cactgaccac cgaacagctc7320gcggcgatggccgggctgga cgaaccgcgg gtccgcgtga tggccgggcg catcgaggtg7380ccacggctgacccgggcgaa ccagccgctc accatccccg cggagaggtc ctggctgctc7440gaacagccccgcagcggcac cctgcaggac ctcgcgctgc tcccgaccga caccggcgac7500cggcccctgcgccccggcga ggtacgcctg gaggtccgcg ccgccggact gaacttccgg7560gacgtcgtggtggcgctcgg catggtcacc gacacgcggc tggccggtgg ggaagccgcc7620ggagtcgtgctcgagaccgg gcccggcgtc accggcttcg ccgtgggaga ccacgtcttc7680ggactgctgggcggcgggtt cgggtcgata gcgatcgccg acagccgcac gctcgcgccg7740atacccgagggatggtcgtt caccacggcc gcctccgtgc cggtggtgtt cgcgactgcc7800tactacgcgctggttgatct ggccgtgctc ggtgcgggtg agtccgtgtt gattcatgcc7860gctgctggtggggtgggtat ggcggcgact cagcttgctc ggcatttggg tgcggaggtc7920tttgcgacggcgagtgcggg gaaacagcat gttcttcgta gggtggggtt ggacgattct7980cgggttgctgattcgcgtac cacggagttt cgggagaagt tcggtggtcg tgttgatgtg8040gtgttgaactcgcttagcgg tgagttcgtt gacgcctcgt tggatgtgtt gtctgacggt8100ggccggtttgtggagatggg taagaccgac atccgggccg gctcgggacg gccgggtgtc8160tcctaccgggcgttcgactt gctggaggcc ggtccggaac gtttgcggga gatcctggct8220gaactgttgacgttgttcga gcggggcgtg ctgcaaccgt tgccggtacg cgcgtgggac8280atccggcaggcgcgcgaggc gttcagctgg atgagccggg ctcggcatgt cggcaagatt8340gttctcaccgttccgcgtcg tcttgatggg gacggcacgg tgttgattac tggtggttcg8400ggtgtgctggccggcattgt ggcgcggcat ctggtgcgtg agtacgacgc ccggcacctg8460ttgctggtctcgcgtagtgc accggatgag ggtttgctgg ctgagctggg tgagcgggcg8520
gaggtggtgctgtgtgacgt ttccgaccgt acggcgctgg agagcgtgct ttccggccgt8580acgttgacggcggtcatcca cacggcgggc gccctggacg acggcgttgt cgaggcgcag8640acgccccaacggatcgactc ggtgttccgc cccaaggttg acggcgcctg gcacctgcac8700gaattgacccggaacatgga cctcgccgcg ttcatcatgt actcgtcggc cgcgggcatc8760atgggcagcgcggggcaggg caactacgcg gcggccaacg ccttcgtgga cgcgttggcc8820gtacagcgtcagcatgaagg tttgccgggc ttggcgctcg cctggggtct gtgggcggac8880gcaagcggcctgaccgccca gctcaccgac gccgaccacg accgcatccg acgcgccggg8940
cagcgcaccatctccgccga gcacgggatg cggctgttcg acggcgcgct gcgccacggt9000gagccgttcctggtgacggc ggcgctcgat ccggtgcgtg agggcgagat cccgccgctg9060ctgcggtcgctgcaccgccc ggtggtgcgg cgggccgtac cggccggcgg tgagtcgtcg9120cagcattggctggttcgctt gacgccggcc gagcgggaag cggcgctgct gaaggccgtt9180tcggaaagcgccgcaacggt gctgggacac gccgacgccc ggtccatccc gccgagcgca9240gtcttccgcgacctggggat ggactcgctg accgcggtcg aactccgcaa caacctggcc9300aaaaccaccggcctgcgcct accggccacg atggcgttcg actatcccac ccccaccgcc9360ctggcgtcccggctcgacga actgctcacc ggcgagaccc cggccccggc ggtcaaatcg9420gaggcacccacgtcgacagc cacggacgag ccgctcgcga ttgtcggtat ggcatgtcgc9480ttgccgggtggggtgtcgtc gccggaggag ttgtggcggt tggtggtgtc gggtggtgat9540gcgatttctgattttccggt ggatcgtggc tgggatgtct cgggtttgcg gggtggcttc9600ctggcgggtgcggctgattt cgatgcggcg ttcttcggga tcagtccgcg tgaggctttg9660gcgatggatccgcagcagcg ggttgttttg gagacgtcgt gggaggcgtt ggagcgggcg9720gggatccggcctgattcgct gcgtggtagt gacaccggtg tgttcatggg tgcctacccc9780ggtgggtacggggtcggggc cgacttgggt ggttttggtg cgaccgcggg tgcggtgagt9840gtcttgtcgggtcgggtctc ttacttcttc gggtttgagg gtccggcgat gacggtggac9900acggcgtgttcgtcgtcgtt ggtggcgttg catcaggccg gttatgcgtt gcggcagggt9960gagtgttcgatcgccttggt tggtggtgtg acggtgatgg cgacgccgca gacgttcgtg10020gagttcgctcggcagggtgg ccttgccgcc gatgggcgta gtaaggcttt cgcggacagt10080gcggacggtgcgggattctc cgagggtgtt ggtgtgctgg tcgtcgagcg gctgtcggat10140gcccaggccaagaaccatca gatccttgct gtggtacggg gttcggctgt caaccaggac10200ggcgcttccaacggtttgac ggcaccgaac ggcccgtcgc agcaacgggt gatccgccag10260gccctcgccaacgcctcgct caaccccgca gacgtcgacg tcgtggaggc gcacggcacc10320ggcaccaccctgggtgaccc gattgaagcc caagcgctgc tggccaccta tgggcagggc10380cgggcggtgccgttgttgct ggggtcggtg aagtccaacg tcggccacac ccaggccgca10440gcaggcgtcgccggtgtcat caagatggtg ctggctctgc agcacggcgt tgttccgcaa10500accctgcatgttgacgagcc gtcgcgacat gttgactggt cggctggttc ggttgagttg10560gcgacgtcgaaccggtcgtt gccttcgttc gatcgtccgt ggcgcgcggg tgtgtcgtcg10620ttcggcatcagcggcacgaa cgctcacgtc atcctcgaag ccgcccctgc ccctgcccct10680gcctttgatcctgattcgac ctccggcgcc acaggccttg ctggagcagc agcgctgccc10740ctggccatctcggcccgctc ggaatcagct ctagccgacc tgacaacccg gctgcgcgcc10800tacctgaccgccaaccccga caccgacctg cacaccaccg ccaccaccct ggccaccaca10860
cgctcatcat tcgaccaccg cgccgtcctg ctcggcgatg acaccatcac cggcaccgcc10920gccgtggatc cgcgtgtggt gttcgtgttc tccggccaag gctcacaacg cgcgggcatg10980
ggcgccgagt tggccgcggc gttccccgtc ttcgccgaca tccatcaacg tgtgtggggc11040ctgctcaatg ttgacgagga cctcaacgtt gacgacacgg gttatgccca gccggcgttg11100ttcgccctgc aggtggcgtt gttcgggttg ctggagtcgt ggggtgtgcg cccggatgcg11160ttgatcggcc attcgatcgg tgagcttgcc gctgcctatg ttgctggtgt ttggtcgttg11220gaggatgcct gcacgctggt gtcggcgcgg gcgcggttga tgcaggcgtt gccgtcgggc11280ggtgtgatgg tggcggtgcc ggtgtcggag gacgaggctc gcacggttct gcgtgatggt11340gtggagatcg ccgcggtcaa cggcccgtca tcggtggtgc tctccggtga cgaggacgcc11400gtgttgcaag cggtcgccgg gttcccacgg tggacccgac tgtcgaccag ccacgccttc11460cactcggcac gcatgaaccc gatgctcgag gagttccgtg cggtcgccga gcagctgact11520taccaccagc cgtcggtcga gatggctgct ggcgagcagg ttgttacgcc ggagtactgg11580gtgcgtcagg tccgtgatgc ggtgcggttt ggtgagcagg tcgcggcgta cgaggacgcg11640gttttcgtgg agatcgggcc gggccgcaac ctcgcccggt tgattgatgg cgttgcgatg11700ctcaacggcg agaacgagac acacgccgca ctgaccggcc tgtcacaact gttcgtccga11760ggcatcatgc ctgactggtc ggcggtgctg ggtgtgagca ccgggcgggt gctggacctg11820ccgacgtacc cgttccagca cgagcggtac tggctgcgcg gcgccgaccg ggtggaagga11880cacccgctgc tggggttgcc ggtgcggctg gcctcgtccg atgaggtggt gttcaccgcc11940aagattttcc gggacagcga ccagtggttg cgggatctgg ctgtcctgcc cgcggcggca12000ttcgtcgaga tcgcggtgtc ggcggcggat gaggtcggct gcggccaggt cgaagagttg12060gtcgtcgagt ccctgccgcg gcttcccgag gacgccgctg tcgaggtgca gacctggatc12120gggggaccgg aggacggggg caggcggcgg ctcaccgtct acgggcggta cacggagacc12180gagccgtgga tcccgcttgc caacggcatt ctgacatccg gcccagcacc gagtcccgac12240cacgcggacc cagcttggcc gccggtggga gcagtgcccg tggacgcgga tgtgccggcg12300tggcggcgcg gcagtgagct gttcgccgaa gtcgccctcg acggggagct ggacgcggcc12360aggttcgcga tgcacccggc cttgctggat gccgctgtcg acgtcgcggg tgacggcgtg12420gcggctgttt ggcgtggcct gactttgcat gcttcgaaag caaccgagct tcgtgttcac12480ctcacggacc acggtgtcgt cgccgtcgat ccagcgggct tgcccgtgct gtcggccggt12540gccctcatcc ggcgacccct tccgatccgg gaacctcact ccagcgacct gctcacggtg12600tcgtggaccg agattccggc gcctgcttct tccacgagtg acgtggctga ggtgttcacg12660gcactgcccg atgacagcac cgacgtattg acccagaccc gcgcgttgac cagtcaagtg12720ttgacggcca ttcagtcatg gcttgatcgt gacgacggca ccctcctcat ccggaccggc12780atgggactgg ccggtgcggc ggtgtcgggg ttggtgcggt cggcacagtc ggagcatccc12840ggccggttcg tgctggtgga aagcgacgat gacgtcgatg gtccggcact ggactcgcct12900gcctcgcccg gatcgtccgt ctggccggga tcgccggctt cgctggcctc gcttgatgag12960ccgcggctgc gtatgaccgg cggccgtatc gaggtgcccc ggctgacccg ggtgagctcc13020gaaccggctg gtgaggctgt gtgggacccg gaaggcacgg tggtcatcac cggtggctcg13080ggtgtcttgg ccgggatcct ggctcgccat ctggtgaacg agaggggtat gcgccgactg13140ctgctgctct cgcgtggtgc gccggatgag gcgctgctca ccgagctggg tgaccgggcg13200
gaggctgctg tttgcgacgtttcggatcgc gccgctctcg agcgggtgct ggcggggcgc13260cggttgacgg cagttgttca taccgccggt gtcattgacg acggcgtgat cgagtcgatg13320atacccgaac gtattgacgcggtgcttcgg gcgaaggttg acggtgcttg gcatctgcac13380gagttgaccc gtgagcaaga gctggccgct tttgtggtgt attcgtcggc ggctggggtg13440
ctgggcagtg ctgggcaggg caactatgcg gccgcgaacg catttgtgga tgcgttggct13500gagcggcgcc gggctgaggg tttgccgggg ctggctgtgg cgtgggggtt gtgggaggac13560agcagtgggc tgacagctca gctgtccgac gccgaccgcg aacgtatgcg gcgtagcggg13620
ttcacctcca tcaccgccga acacggcatg cgcttgttgg acatggccct gcgtcaccgt13680gaaccggccg tggttgcggcgccgacgact gcggtaggcg acggcgaagt cccggcgctg13740ctgcgttcct tgcaccgtacgggaagccgg aggaaggcat cgaccggcgc ggggcagtgg13800ctcgtcggcc tttcgccggtggagcgggaa cgggcgctgt tgacggctgt gcgggacaac13860gccgcagtcg tcctgggaca ccacggagct cgggccatcc cggcgaacgc cgccttccga13920gatctcggga tggactcgctgaccgccgtc gaactgcgca acagtctggc gaagaccacc13980gggctgcggc tgccggcgacgttggtgttc gactacccga ccccggcggc cctcgccgcc14040cggctcgacg agctgctggtcggccgtgcc gccgctcccg cccgtcgagc agcttcagcg14100gtgggccagg acgagccgctggcgatcgtg ggtatggctt gccggttgcc gggtggggtg14160tcgtcgccgg aagacctgtg gcggctggtc gagtcgggca cggacgcgat ttccggtttc14220ccgactgacc gtggctggga cgtcgagaac ctgttcgatc cggatccgga tgcggcgggt14280aagacatatt gcgtgcaggg tggtttcctg gacacggcgg cggagtttga tgccgggttc14340ttcgggatca gtccgcgtga ggccttggcg atggatccgc agcagcggct ggtgctggaa14400gcctcgtggg aggcgttcga gcgggccggc atcgaccccg gttcgatgcg cggcagcgac14460accggcgtgt tcatcggcgcctaccccggc gggtacggcg tcggcgtcga gttcggcggc14520ttgggtgcga cggcgggagcgggcagcgtg ctctcgggcc gggtgtccta cttcttcggc14580ctcgaaggtc cggcgatgacggtggacacg gcgtgttcgt cgtcgttggt ggcgttgcat14640caggccgggt acgcgctgcg gcagggcgac tgttcgctgg ccctcgtcgg cggggtcacc14700gtgatgtcta cgccgcacattttcgtggaa ttctcgcgtc aacgcgggct ctcggtggac14760gggcggtgca aggcgttcgg ggacggcgcc gacggcacgg gctgggccga gggtgtcggc14820gtgctgctcg tcgagcggctgtcggacgcg cgccgtaacg ggcaccgggt cctcgcggtg14880gtcaagggtt cggctgtcaa ccaggacggt gcatccaacg ggttgacggc gccgaacggg14940ccgtcgcagc agcgggtgatcgaggctgcg ctcgccagcg cgggcctcag cgcggcggat15000gtcgacgtcg tggaagccca tggcacgggt acgacgctgg gtgatccgat cgaggcgcag15060gcggtcctcg ccacgtacgg tcaaggtcgc tcgacgccgt tgttgctggg ctcgctgaag15120tcgaacatcg ggcacactca ggctgccgct ggtgtggctg gtgtgatcaa gatggtgatg15180gcgcttcaac acggggtcgttccacagact ttgcatattg acgtgccgtc gcgtcatgtt15240gactggtcgg ctggtgcggttgacgtggtc acgtcgaatc aaccgtggcc gtcgtcgggt15300cggccggggc gtgctggtgtgtcggcgttc ggggtcagtg gcaccaacgc gcacgtgatt15360ttggagagtg cgccggacga gccggtctcg gaggttgccg gtccggcgcc ggtggtcgcg15420gatgtggtgc cgctggtgctgtctgctcgc actgtgccgg ctttgggtga gcttgaggct15480cgggtgcgcg cctatgtggcggcggccgag gatgacaggg ctgttgctgc gacgttggcg15540
tggtctcggg cggtgttcga gcacagggct gtgctgatcg gtgaagacac catcaccggg15600gtggctgcgg tcgatccgcg ggtggtgttc gtgttcccgg gccagggctg gcagtggctg15660ggcatgggtg tccagctacg cgactcgtcg gtggtgttcg cctcacgcat ggccgagtgt15720 gctgccgcgt tgagcgagttcgttgactgg gacctgtttg ccgctctaga cgacccggcg15780gtggtggatc gggttgatgtagtccagccg gtgtgctggg ccgtcatggt gtcgctcgcc15840gctgtctggc aggccgctgg tgtcaccccc gacgccgtcg tcgggcactc ccagggcgag15900atcgccgctg cggtggtggcgggttcgctg tctctgcgcg acggcgcgag ggtggtggcg15960cagcgcagcc agctgatcgcacaaggcctg gccggtcacg gcgccatggc ctccatcgcc16020ctgcctgccg acgagatcaccctggtcgac ggtgcctgga tcgcggcgct caacggcccg16080gcatccacgg tgatcgcggg cacgcccgaa gcggtcgagg cggtgcttgc cgctcaggat16140gcccgggtgc ggcggatcgcggtggattat gcctcgcata ccccgcaggt tgaggcgatt16200cgtgatgagt tgctggcgttgaccgctgat gttgactcgc aggcccctgc tgtgccgtgg16260ttgtcaactg ttgacggcgcgtgggtggat ggcccgctga gtgtggacta ctggttccgt16320aatctgcgcg agcaggtcgg ttttgcgcag gcggtgcaga cgctgggtga tgcggtgttc16380gttgaggtgt cggcgagtccggtgttgatg cagtcgatgg ttgatgcggt cacggtgccg16440acgttgcggc gtgatgatgg cagtccggcc cggctggtga cttcgctggc tgaggcgttc16500gtgcagggcg tcgacgttga ttgggcggcg gtgctggggg cgggcgctga gcgggcgctg16560gacctgccga cgtatcccttcgaccgtcag cggtattggg ttgtcgctga ccgggtgagc16620ggggatgtgt cgggtgctgg tctgggcacg gtggagcatc cgttgctggg tgcggtggtg16680gcgttgccgg gctcggacgg gttggtgttg acgggtcggg tgtcgttggc gacgcacggt16740tggcttgccg atcatgcggtgcggggcagt gtgttgatgc cgggtaccgg gtttgttgag16800ctggtggtgc gggccgctga cgaggtcggc tgtgatgtcg tcgacgagtt ggtgagcgaa16860gcgcctctga tcgtcccggctgctggtgga gtccagctgt ccctggcggt tggcgaagcg16920gatgagggcg ggcgccggca agtcaccttg ttctcccggg cggatgacgc cgacgagtgg16980gttcggcatg ttacggcgaccatcagtgcc tccggggccg cgcttgcgac gccgctgctc17040gccgaatggc cgcctgccgg ggccgagtcg gtggacgtga ccggcttcta cgaacggctc17100gcggctgcgg gacacgagta tggcccggcc ttccaagggt tgcaggtcgc ctggcgtgcg17160ggggacaccg tctacgcaga ggtcgcgctc gccgaggagc aggagcgcga ggcggcacgg17220tacgcagtgc accccgcgctgctcgacgcc gcactgcacg ccgggatggt gagcggattc17280caggccgacg gcactgtgcg gttgccgttc acttggaaca acgttcgtgt gcagggcacc17340gggccgaagc ggctccgggtggccaccacg cgggggagcc tgcagcttgc cgacgagcag17400gggcgaccgg tggccggcatcggctcgctc gtgacccgcc ggatcgccga tgacaatcaa17460ctgttgaccg tgacatggacggaagtcacg gccggggcac ccgtcaacga tgctgaggtg17520ttcacggctc tccccggcaa cagcgccgat gtgctggcgg agatccgtac gttgacggaa17580cggttttccg aagcgatcca ggcatggctc gtacgggacg acgggacgct gatcgtccgg17640accggcacag ggttgcccag cgcggcaata tcggggctgg tgcggtcggc gcagtcggag17700tatccgggcc ggttcgtgctcgtggagagc gacgacgaaa ccctgccgga cctgaccgcg17760ctggtctcgc tggacgaaccacagctgcgt atcaacgacg gccgcatcga ggtgccgcgg17820ctgacgcggg tgacggccga accggtcgag cagactgcct gggatccgga tggcaccgtc17880
ctgatcaccg gtgatcaggctggccatgtt gcccgtcatc tggtgactgg gcgtgggatg17940cgtaacctgc tgctgctcccgaccggtgcc ccggacgaga ccctggtcga cgagctgacg18000aagctgggcg cgaaggttga ggtcgcggcg tgtgacctga cggatcgggc tgcgctggcc18060gaggtgctgg cggatgcaccggcgttgacg gtcgtcatcc acacggccgg cgctcccgac18120ggggacacga catcgctgatcgccagctcc tggcatctgc acgagttgac acgtgatcgc18180ggtctggcgg cgttcatcctgtactcgtcg gttgacgggt tgatgggcgc tgctcggcgg18240agcagctacg catttgtgga cgctctcgcc gtacaccgga gggatgaagg tctgccgggt18300ctttcccttg cctggggcga gatctccgcc gaagacgcga tgcgtgcgtt cgacagtgcg18360actcggcaga gcctgccgttggtggtcgct ggtgcggtca cgtccgctcg tgggggtgag18420attccggcgc tgctgcggtcgttgcgccgc ccgctcgtac ggcgcacggg gccggccgcc18480ggtgactcgc cactggccgccctgccgccg gcggaacggg agaaagcgct ggtgagggtg18540gtctgcgcga gcgctgcggcggtgctgggc catgccgaca cccgcgcggt accggccacg18600gcggcgttca aggatctggg cctggactcg ctcaccgcgg tggatctgcg caacagcctc18660ggcaaggcca ccgggctgca gctgccggcc acgctggtgt tcgattaccc aactccgacc18720gcgttggccg cgcggctggccgagctgctc accggtgaga gcgcgacgcc cgtacggaaa18780tcagcggtgt ccgcgtcgctggatgagccc ctcgcgatcg tgggcatggc ttgccggttg18840ccgggtggag tcgcatcgccggaggacctg tggcggctgg tggagtcggg cacggatgcg18900atttccgagt ttccggcgga tcggggctgg gatgtggacg ggttgttcga tccggatccg18960gatgcggcgg gcaagacgta ttgcgtgcag ggcggtttcc tggatgcggc tggtgagttc19020gatgccgggt tcttcgggatcagtccgcgt gaggcgctga tgatggatcc gcagcagcgg19080gtgttgctgg aggcgtcgtg ggaggcgttc gaacgcgcgg gcatcgagcc gacttcagtg19140cgtggcagcg acaccggcgtgttcatcggt gcgttcccgg tcggttacgg cgctggagtc19200gaccacgagg gctataccgcgactgcgggt gtgggcagcg tgctgtcagg ccggttgtcg19260tacttcttcg ggctcgaagg cccagccatg acaatggata cggcgtgttc gtcgtcgttg19320gtggcgttgc atctggcggcgcaggcgttg cgtaatggtg agtgttcgtt ggcgttggcc19380ggtggtgtga cggtgatggcgacgccggag gtgttcaccg agttcgcccg ccagcgcgga19440ctggcagcgg acggccggtg caagccgttc gctgatgcgg ccgatggagc cggcttctcc19500gagggcgcgg gcttgctggtggtggaacgg ctttccgacg cgcgtcgtaa cgggcaccag19560gtgctggcgg ttattcgtgg atccgctgtc aatcaggacg gtgcatcgaa cggcttgaca19620gcaccgaacg ggccgtcgca gcagcgcgtc atccggcagg cgctggccaa cgccgggctg19680agttccgctg atgtcgatgtgctggaggcc cacggtacgg gtacgacgct gggtgatccg19740atcgaggcgc aggcggtcctggccacgtat gggcaggatc gttcggcgcc gttgttgatg19800gggtcgttga agtcgaacatcgggcacact caggcggctt cgggtgtggc tggtgtgatc19860aagatggtga tggcgttgcg gcatggggtg gtgccgcagt cgcttcatgt tgacgagttg19920tcgcgacatg ttgactggtcggccggtgcg gttgatgtgg tcacgtcgaa tcaaccctgg19980ccgtcgtcgg atcggccgcg ccgtgcgggt gtgtcagcct tcggggtcag cggcacgaac20040gttcacgtga tcctggagag tgcgccggtt gagtcggtgg ctgaggtcgc tggtgcggcg20100ccggtggtgg cggatgtggtgccgttggtg ctgtcggcga ggtcggcgcc ggcgttgagt20160gttcttgagg cgcgggtgcg cgcgtatgta gcggcggcgg agaatgaaag ggctgttgct20220
gcgacgttgg cgtcgtctcg cgcggtgttc gagcacaggg ctgtgctgat cggtgacgac20280agcgttgttg gggcggcggcggtcgacccg cgtgtggtgt tcgtattccc cggccagggc20340tggcaatggc tcggcatggg cgtccagcta cgcgactcgt cggtggtatt cgcctcccgc20400 atggccgaat gtgctgccgccttgagcgag ttcgttgact gggacctgtt tgccgccctc20460gacgacccgg ctgtagtgga tcgggttgat gtggtccagc cggtgtgctg ggccgtcatg20520gtgtcgctgg ccgcggtgtg gcaggccgct ggtgtcggcc ccgacgccgt cgtcgggcac20580tcccagggcg agatcgctgctgcggtggtc gcggggtcgc tgtcgttgcg tgatggcgct20640cgggtggtgg cgcagcgtag tcagttaatt gcgcgtggcc tggccggtca cggtgcgatg20700gcctcgattg cgctaccggctgatgagatc acgctggttg agggtgcgtg ggtcgcggcg20760ctcaacggtc cggcttccacggtgatcgcg ggcacgccgg atgcggttga ggcggtgctt20820gccgcccagg acgcgcgggtgcggcggatc gcggtggatt atgcctcgca taccccgcag20880gttgaggcga ttcgtgatga gttgctggcg ttgaccgctg atgttgactc gcaagctcct20940gctgtgccgt ggttgtcaactgttgacggc gcgtgggtgg atggcccgct gagtgtggac21000tactggttcc gtaacctgcg cgagcaggtc ggttttgcgc aggcggtgca gacgctgggt21060gatgcggtgt tcgttgaggtgtcggccagt ccggtgttga tgcagtcgat ggttgatgcg21120gtcacggtgg cgacgttgcg gcgtgatgat ggatcggcca ctcggctggt gagctcgctg21180gctgaggcgt tcgtgcaggg cgtcgatgtt gattggacgg cggtgctggg ggccggcggc21240gtgcgggtgc tggatctgccgacgtatccg ttccagcggc agcatttctg ggcgctgccc21300gatcaaacgg ctggtgatgtgtcgggtgcg ggtttggacg cggtgcggca tccgttgctg21360ggtgcggtgg tggcgttgccgggttccgac gggttggtgt tgacgggtcg ggtgtcgttg21420gcgacgcatg cctggttggcggatcatgcg gtgcggggca gtgtgttgat gccgggtacc21480gggtttgtgg agctggtggtgcgggccgct gacgaggtcg gctgtgatgt cgtcgacgag21540ctggtgatcg aggcgccgttgcggttgccc acggccggtg gggtgcagct gtccgtgtcg21600gtcggggagg ccgacgaggg tgggcgtagg caggtgacgg tccactcgcg tacggatgcg21660gctgaaacct ggacccggca cgtgaccgcc acggtcagca acgccgaagc gagcggccct21720ccgccggacc tgcggcagtg gccgccggcg aacggcactc cggtggacgt ctcaggcttc21780tacgacgcgc tcggtggcta cgagtacggg ccggcgttcc aggggctgcg ggctgcctgg21840aaggtggggg agacgatcta cgccgaggtc gctctggctg aggagcagcg ggccgaagcg21900gcgcggttcg gggtgcacccggcgttgctg gatgctgctc tgcacgcgat catgctgggt21960tccgctgagg gtgacggctcggtgcagttg ccgttctcgt ggagcggtgt gcgggttcat22020gctgctgggg cggctgcgttgcgggtcgtg gtggatcggg ggagtctgcg gctggcggac22080gagtccggtc ggccggttgccactgttgat gcgttggtga cgcggccgat ggctgacgac22140gtggccgatg atctgctcgcggtgtcgtgg accgagattg cggctgggcc ggtcggtgac22200gacgtcgagg tgttcacggcgcttcccggg gacggtgacg tgctggcgga gtcgcgtggg22260ttgacagggc gggtcttggcggcgatccag gcgtggctgg gtcgtgacga cgggacattg22320gtcatccgta cgggcaccgg gctggcgagt gcggcggtgt cggggctggt gcgctcggcg22380cagtcggagc atccgggccg gttcgtgctg gtggaaagcg atgatgtggt gaccgccggg22440cagctgtcga gcgtggccgg gttggacgag ccgcggttgc ggatcgtgga cggccgggtg22500gaggtgcccc ggctgacccg ggtggttgcc gagccggtcg aggcgcccgg gtgggatccg22560
gacggcacgg tgttgatcac cggtggttcc ggggtgctgg ccggcattgt ggcgcggcat 22620gtggtggccg aacggggtgt gcggcgggtg ctgctgctgt ctcgaaccgc gccggatgag 22680gtgctggtcg ctgacttgac tgacctgggt gccgaggtcg acgtggcgag gtgcgacgtg 22740tcggatcggg ctgcgctggc cgaagtgttg gcgggtgttc cggtgttgac tgcggtgatt 22800catacggcgg gtgtgctgga cgacggtgtc atcgagtcgt tgaccccgga gcggctggac 22860ggggtgttcc ggccgaaggt tgacggtgct tggcatctgc atgagttgac tcgtgatcgt 22920gatctggcgg cgttcgtggt gtattcgtcg gctgctggag tgctgggtag tgcggggcag 22980 ggcaactatg cggcagctaa tgctttcctg gacgctctgg ccgtacagcg aaggcttgag 23040gggttgccgg ggttggcgtt ggcctggggg ttgtgggcgg acgcgagcgg gctgaccgcg 23100acgatgaccg acgccgatcg cgaccggatc cggcgcggtg gcctgcgtgc catcaccgcc 23160gagtacggca tgcggctgtt cgacacggcg atgcaccgcg aggagccgat gttgatcgcg 23220gcggcgatcg ggacgccacg cgacgggcag gtgcccgccc tgctgcgctc gttgcatcgc 23280ccggtggccc ggcgctccgc tgcccctcgc gactcgtcgg cgcagtggct ggccaccttg 23340gcaccggagg aacgcgacgc cgcgctgctg caactggtgt gtgacagcgc cgcggtcgtg 23400ctgggccatg gcgatgggag tgccatcccg gtgaccgcga ctttcaagga cctgggagtg 23460gactcgctga ctgccgtgga ggtccgcaac cggctggcag cggccaccgg actgcggctg 23520ccggccacga tggtgttcga ctacccgacg cccggcgtgc tggcggctca cctcggtgtg 23580ctgttcgccc caccggaacc cgaacccaac gacatccagg agcgggagct gcgccgcgcg 23640ctcgccgcga tctcggtggc caagttccgc gaggccggcg tgctggacac gctgctccgg 23700ctggccgccg gggagacaaa gcccgacacc ggcggggatt ccggcgacga cgaagcgctc 23760gtcgacgaga tggacgccga tgctctgatc aagcacgtgc tggaggcagg acgatga 23817<210>2<211>7938<212>PRT<213>Actinoplanes<400>2Met Ser Arg Ala Glu Leu lie Arg Pro Leu His Glu Leu Leu Arg Val151015Asn Ala Gly Arg Arg Gly Asp Lys Val Ala Tyr Ala Asp Ser Arg Arg202530Ser Val Thr His Ala Glu Leu Leu Leu Arg Thr Gly Arg Leu Ala Gly354045His Leu Ala Gly Leu Gly Val Glu Arg Gly Asp Arg Val Ala lie Leu505560Leu Gly Asn Arg Val Glu Thr Met Glu Ser Tyr Leu Ala lie Ala Arg65707580Ala Gly Ala lie Ala Val Pro Leu Asn Thr Glu Ala Ser Asp Ala Glu859095lie Glu His Cys Leu Ser Asp Ser Gly Ala Val Ala Val Leu Thr Gly
100105110Glu Ala His Leu Asp Leu Val Arg Arg Val Ala Pro Ala Ala Ala Ala115120125Val Pro Ala Gly Asp lie Asp Glu Leu Ala Gly Thr Glu Pro Val Thr130135140Pro Ala Arg Asp Asp Leu Arg Leu Asp Glu Pro Ala Trp Met Leu Tyr
145150155160Thr Ser Gly Thr Thr Gly Thr Pro Lys Gly Val Val Ser Thr Gln Gly165170175Ser Gly Leu Trp Ser Ala Ala Asn Cys Asp Val Pro Ala Trp Gln Leu180185190Thr Glu Asp Asp Val Leu Leu Trp Pro Ala Pro Leu Phe His Ser Leu195200205Ala His His Leu Cys Leu Leu Ala Val Thr Ala Val Gly Ala Thr Ala210215220Arg lie Leu Gly Thr Phe Val Ala Gly Glu Val Leu Asp Gln Leu Arg225230235240Glu His Asn Cys Thr Val Leu Val Gly Val Pro Thr Met His Arg Tyr245250255Leu Val Ala Ala Ala Gly Ala Gly Gly Ala Arg Thr Pro Ala Leu Lys260265270Met Gly Leu Val Ala Gly Ala Val Ala Pro Pro Ala Leu lie Gln Gly275280285Phe Glu Asp Val Phe Gly Val Pro Leu Leu Asp Thr Tyr Gly Cys Thr290295300Glu Thr Thr Gly Ser Leu Thr Val Asn Trp Leu Asp Gly Pro Arg Val305310315320Pro Gly Ser Cys Gly Leu Pro Val Pro Gly Val Ala Leu Arg Phe Val325330335Asp Pro Val Thr Gly Ala Asp Val Pro Ser Gly Ala Glu Gly Glu Leu340345350Trp Ala Arg Thr Pro Ser Val Met Ser Gly Tyr His Gly Gln Pro Asp355360365Ala Thr Ser Glu Val Leu Thr Asp Gly Trp Tyr Arg Thr Gly Asp Leu370375380Ala Arg Gln Ser Ala Ser Gly His Val Thr lie Thr Gly Arg lie Lys385390395400Glu Leu lie lie Arg Gly Gly Glu Asn lie His Pro Arg Glu lie Glu405410415
Thr Val Ala Leu Asp Val Pro Gly Val Lys Asp Ala Ala Ala Ala Gly420425430
Arg Arg His Pro Val Leu Gly Glu lie Pro Ala Leu Tyr Val Val Ala435440445Glu Pro Gly Gly Val Asp Ala Glu Ala Val Leu Asp Arg Cys Arg Asp450455460Arg Leu Ser Tyr Phe Lys Val Pro Glu Glu lie Tyr Gln Val Ala Ala465470475480lie Pro Arg Thr Ala Ser Gly Lys Val Arg Arg Asn Arg Leu Thr Gln485490495Glu Pro Ala Glu Leu Leu Ala Gly Ala Ala Gly Thr Glu Ser Leu His500505510Arg Leu Glu Trp Thr Pro lie Asp Leu Pro Ala Val Ser Leu Ala Glu515520525Arg Pro Gln Asp Ala Ala Arg Val Arg Thr Thr Arg His Ala Val His530535540Val Thr Thr Gly Asp Leu Pro Asp Pro Gly Gln Ala Ala Arg Trp Asp545550555560Ala Tyr Arg Ala Glu Pro Asp Val Val Leu Val Asp Leu Asp Asp Thr565570575Asp Pro Gly Asp Ala Val Leu Ala Thr Leu Ala Gly Leu Gly Glu Pro580585590Leu lie Ala Leu Arg Glu Gly Lys Ala Tyr Val Ala Arg Leu Ala Asp595600605Ala Ala Ser Arg Ser Leu Thr Val Pro Ala Asp Arg Ala Trp Val Leu610615620Arg His Pro Ser Ser Gly Thr Leu Arg Asp Leu Ala Leu Val Ala Asp625630635640Asp Thr Ala Gly Arg Ala Leu Gln Pro Gly Glu Val Arg Leu Ala Val645650655Arg Ala Ala Gly Leu Asn Phe Arg Asp Val Leu lie Ala Leu Gly Thr660665670Tyr Pro Gly Glu Gly Val Met Gly Gly Glu Ala Ala Gly Val Val Leu675680685Glu Val Gly Pro Gly Val Thr Gly Leu Asn Pro Gly Asp Arg Val Phe690695700Gly Leu Val Thr Ala Ala Phe Gly Pro lie Ala lie Thr Asp His Arg705710715720Thr Leu Gly Val lie Pro Ala Asp Trp Ser Phe Ala Thr Ala Ala Ser
725730735Val Pro lie Val Phe Ala Thr Ala Tyr Tyr Gly Leu Val Asp Leu Ala740745750Ala Leu Gly Ala Gly Glu Ser Val Leu lie His Ala Gly Ala Gly Gly755760765Val Gly Met Ala Ala Thr Gln lie Ala Gln His Leu Gly Ala Arg lie770775780 Phe Ala Thr Ala Ser Ala Gly Lys His His lie Leu Arg Thr Ala Gly785790795800Leu Ala Glu Asp Gln lie Ala Asp Ser Arg Thr Thr Gly Phe Gln Asn805810815Val Phe Pro Arg Gly Leu Asp Val Val Leu Asn Ser Leu Ser Gly Glu820825830Phe Val Asp Ala Ser Val Ser Leu Leu Ala Asp Gly Gly Arg Phe Leu835840845Glu Met Gly Lys Thr Asp lie Arg Asp Ala Asp His Val Val Ala Asp850855860Arg Pro Gly Ala Thr Tyr Gln Ala Phe Asp Leu Leu Asp Ala Gly Pro865870875880Asp Arg Leu Arg Glu lie lie Ala Glu Leu Leu Asp Leu Phe Ala Arg885890895Gly Val Leu Arg Pro Leu Pro Leu Arg Ala Trp Asp lie Arg Gln Ala900905910Arg Asp Ala Phe Ser Trp Met Ser Arg Ala Arg His lie Gly Lys Met915920925Val Leu Thr Val Pro His Gly Leu Asp Ala Asp Gly Thr Val Leu lie930935940Thr Gly Asp Ser Gly Phe Arg Ala Gly Arg Val Ala Arg His Leu Val945950955960Ser His His Gly Val Arg His Leu Val Leu Asp Thr Gly Gln Pro Val965970975Asp Glu Thr Leu Val Ala Glu Leu Thr Ala Leu Gly Ala Ala Val Thr980985990Pro Thr Ala Gln His Pro Leu Thr Ala Val Val His Thr Gly Gly Pro99510001005Gly Leu Ala Ala Leu Asp Gln Gln Thr Arg Ser Leu Asp Leu Ala101010151020Ala Phe Val Ala Phe Ser Glu Asp Ala Pro Ala Thr Val Glu Ala102510301035
Leu Thr Arg Arg Arg Arg AlaAsp Gly Phe Pro Ala Thr Ala lie104010451050
Ala Trp GlyLeu Pro Glu GlyGlu Pro Ala Ala lie Arg Gly Glu105510601065Leu lie GlyArg Ala Leu AlaAla Pro Asp Pro Ala Tyr Val Val107010751080Thr Arg lieAsn Thr Ala GlyLeu Arg Ala Leu Ala Ala Ala Gly108510901095Glu Leu ProPro Val Leu ArgAsn Leu Ala Ala Arg Arg Asp Gln110011051110Pro Gly ThrArg Thr Gly GluArg Thr Arg Thr Gly Leu Leu Asp111511201125Leu Val Arg Arg Ser lie lieAsp lie Leu Gly Pro Ala Ala Gly113011351140Glu Arg PheAla Pro Gly ArgThr Phe Arg Glu Thr Gly lie Asp114511501155Ser Leu ThrAla Val Glu LeuArg Asn Ser Leu Ala Gln Ala Thr116011651170Gly Leu ProLeu Pro Ala ThrLeu Val Phe Asp Tyr Pro Thr Pro117511801185Ala Val LeuVal Ala Arg LeuGlu Glu Leu Thr Gly Gly Ala Pro119011951200Gly Thr SerAla Pro Val SerAla Thr Val Gly Gln Asp Glu Pro120512101215Leu Ala lieVal Gly Met AlaCys Arg Leu Pro Gly Gly Val Ser122012251230Ser Pro GluAsp Leu Trp ArgLeu Val Glu Ser Gly Thr Asp Ala123512401245lie Ser GlyPhe Pro Val AspArg Gly Trp Asp Val Asp Gly Leu125012551260Phe Asp ProAsp Pro Asp AlaVal Gly Lys Thr Tyr Cys Val Gln126512701275Gly Gly PheLeu Asp Thr AlaAla Glu Phe Asp Ala Ala Phe Phe128012851290Gly lie SerPro Arg Glu AlaLeu Ala Met Asp Pro Gln Gln Arg129513001305Leu Val LeuGlu Ala Ser TrpGlu Ala Phe Glu Arg Ala Gly lie131013151320Glu Pro GlySer Val Arg GlySer Asp Thr Gly Val Phe Met Gly
132513301335Ala PheAla Gly Gly Tyr Ala Ala Asp LeuGlu Gly Phe Gly Ala134013451350Thr AlaGly Ala Thr Ser Val Leu Ser GlyArg Val Ser Tyr Phe135513601365Phe GlyPhe Glu Gly Pro Ala Met Thr ValAsp Thr Ala Cys Ser137013751380 Ser SerLeu Val Ala Leu His Gln Ala GlyTyr Ala Leu Arg Gln138513901395Gly GluCys Ser Leu Ala Leu Val Gly GlyVal Thr Val Met Ala140014051410Ser ProGln Ser Phe Val Glu Phe Ser ArgGln Arg Gly Leu Ala141514201425Ala AspGly Arg Ser Lys Ala Phe Ala AspAla Ala Asp Gly Thr143014351440Gly TrpAla Glu Gly Val Gly Val Leu LeuVal Glu Arg Leu Ser144514501455Asp AlaGln Ala Gln Gly His Gln Val LeuAla Val Val Arg Ser146014651470Ser AlaVal Asn Gln Asp Gly Ala Ser AsnGly Leu Ser Ala Pro147514801485Asn GlyPro Ser Gln Gln Arg Val lie ArgGln Ala Leu Ala Asn149014951500Ala ValLeu Thr Ala Ala Asp Val Asp ValVal Glu Ala His Gly150515101515Thr GlyThr Thr Leu Gly Asp Pro lie GluAla Gln Ala Val lie152015251530Ala ThrTyr Gly Gln Asp Arg Ser Thr ProLeu Leu Leu Gly Ser153515401545Leu LysSer Asn lie Gly His Thr Gln AlaAla Ala Gly Val Ala155015551560Gly Vallie Lys Met Val Met Ala Leu ArgHis Gly Val Val Pro156515701575Arg SerLeu His Val Asp Val Pro Ser ArgHis Val Asp Trp Ser158015851590Ala GlyAla Val Asp Val Val Thr Ser AsnGln Pro Trp Pro Ser159516001605Ser AspArg Pro Gly Arg Ala Gly Val SerAla Phe Gly Val Ser161016151620
Gly Thr AsnAla His Val lieLeu Glu Ser Ala Pro Phe Glu Pro162516301635Ala Asp Glnlie Ala Gly ProVal Pro Val Val Ala Asp Val Val164016451650Pro Leu ValLeu Ser Ala ArgThr Val Pro Ala Leu Thr Glu Leu165516601665Glu Ala Arg Val Arg Ala TyrVal Ser Ala Ala Glu Asp Asp Arg167016751680Ala Val Ala Ala Thr Leu AlaSer Ser Arg Ala Val Phe Glu His168516901695Arg Ala ValLeu lie Gly GluAsp Thr Val Asn Gly Ser Ala Leu170017051710Ser Asp ProArg lie Val PheVal Phe Pro Gly Gln Gly Trp Gln171517201725Trp Leu GlyMet Gly Val AlaLeu Arg Asp Ser Ser Val Val Phe173017351740Ala Ser Arg Met Ala Glu CysAla Ala Ala Leu Ser Glu Phe Val1 74517501755Asp Trp AspLeu Phe Ala AlaLeu Asp Asp Pro Ala Val Val Asp176017651770Arg Val AspVal Val Gln ProVal Cys Trp Ala Val Met Val Ser177517801785Leu Ala Ala Val Trp Gln AlaAla Gly Val Thr Pro Asp Ala Val179017951800Val Gly HisSer Gln Gly Glulie Ala Ala Ala Val Val Ala Gly180518101815Ser Leu SerLeu Arg Asp GlyAla Arg Val Val Ala Leu Arg Ser182018251830Gln Leu lieAla Gln Gly LeuAla Gly Arg Gly Ala Met Ala Ser183518401845lie Ala LeuPro Ala Asp Glulie Thr Leu Val Glu Gly Ala Trp185018551860lie Ala Ala Leu Asn Gly ProVal Ser Thr Val lie Ala Gly Thr186518701875Pro Asp Ala Val Glu Ala ValLeu Ala Ala Gln Asp Ala Arg Val188018851890Arg Arg lieAla Val Asp TyrAla Ser His Thr Pro Gln Val Glu189519001905Ala lie Arg Asp Glu Leu LeuAla Leu Thr Ala Asp Val Asp Ser
19101915 1920Arg Ala ProAla Val Pro TrpLeu Ser Thr Val Asp Gly Thr Trp19251930 1935Val Asp GlyPro Leu Ser ValAsp Tyr Trp Phe Arg Asn Leu Arg19401945 1950Glu Gln ValGly Phe Ala GlnAla Val Asp Val Leu Ala Gly Thr19551960 1965
Gly Pro AlaAla Val Gly GluAla Val Phe lie Glu Val Ser Ala19701975 1980Ser Pro ValLeu Met Gln SerMet Val Asp Ala Val Thr Val Pro19851990 1995Thr Leu ArgArg Asp Asp GlySer Ala Thr Arg Leu Val Thr Ser20002005 2010Leu Ala GluAla Phe Val GlnGly Val Ala Val Asp Trp Ala Ala20152020 2025Val Leu GlyAla Gly Ala GluArg Val Leu Asp Leu Pro Thr Tyr20302035 2040Pro Phe GlnArg Gln Arg PheTrp Ala Leu Pro Asp Arg Ala Ser20452050 2055Gly Asp ValAla Gly Leu GlyLeu Asp Ala Val Gln His Pro Leu20602065 2070Leu Gly AlaVal Val Ala LeuPro Gly Ser Asp Ser Val Val Leu20752080 2085Thr Gly ArgVal Ser Leu AlaThr His Ser Trp Leu Ala Asp His20902095 2100Ala Val ArgGly Thr Val LeuMet Pro Gly Thr Gly Phe Val Glu21052110 2115Leu Val ValArg Ala Ala AspGlu Val Gly Cys Gly Val Val Asp21202125 2130Glu Leu Vallie Glu Ala ProLeu Arg Leu Pro Val Ala Gly Gly21352140 2145Val Gln LeuSer Val Pro ValGly Glu Ala Asp Glu Gly Gly Arg21502155 2160Arg Gln ValThr Val His SerArg Thr Asp Ala Ala Asp Thr Trp21652170 2175Thr Arg HisVal Thr Gly ThrVal Ser Ala Ala Ser Ala Pro Ala21802185 2190Thr Thr ProAsp Leu Ala AlaTrp Pro Pro Gly Gln Ala Gln Pro21952200 2205
Val Asp LeuSer Gly Phe TyrAsp Glu Leu Ala Ala Val Gly Tyr221022152220Glu Tyr GlyPro Ala Phe GlnGly Leu Arg Ala Ala Trp Arg Ala222522302235Gly Asp ThrVal Tyr Ala GluVal Ala Leu Ala Asp Ala Leu Val224022452250
Gln Asp Ala Gly Arg Phe AlaVal His Pro Ala Leu Leu Asp Ala225522602265Ala Leu HisThr Gly Leu LeuThr Gly Pro Asp Asn Arg Gln Gly227022752280Val Arg LeuPro Phe Ser TrpAsn Asn Val Ser lie His Ala Ser228522902295Gly Pro Ala Arg Leu Arg ValThr Met Thr Gly Glu Gly Leu Arg230023052310Leu Ala AspGlu Phe Gly HisPro Val Ala Glu lie Gly Ala Leu231523202325Val Thr Arg Pro Met Thr AspAsp Ala Val Thr Asp Leu Leu Ala233023352340Val Thr TrpThr Glu lie ProAla Val Ala Ser Ala Thr Gly Ala234523502355Glu Val PheThr Ala Leu ProSer Asp Ala Ala Ala Asp Val Pro236023652370Ala Glu ThrArg Ala Leu ThrVal Arg Thr Leu Ala Ala lie Gln237523802385Ser Trp LeuAsp Arg Asp AspGly Thr Leu Val lie Asn Val Asp239023952400Thr Gly LeuThr Gly Ala AlaVal Ser Gly Leu Val Arg Ser Ala240524102415Gln Ser GluHis Pro Ser ArgPhe Val Leu Val Glu Ser Asp Asp242024252430Ala Leu ThrThr Glu Gln LeuAla Ala Met Ala Gly Leu Asp Glu243524402445Pro Arg ValArg Val Met AlaGly Arg lie Glu Val Pro Arg Leu245024552460Thr Arg Ala Asn Gln Pro LeuThr lie Pro Ala Glu Arg Ser Trp246524702475Leu Leu GluGln Pro Arg SerGly Thr Leu Gln Asp Leu Ala Leu248024852490Leu Pro ThrAsp Thr Gly AspArg Pro Leu Arg Pro Gly Glu Val
249525002505
ArgLeuGluValArgAlaAlaGlyLeuAsnPheArgAspVal
251025152520
ValAlaLeuGlyMetValThrAspThrArgLeuAlaGlyGly
252525302535
AlaAlaGlyValValLeuGluThrGlyProGlyValThrGly
254025452550
AlaValGlyAspHisValPheGlyLeuLeuGlyGlyGlyPhe
255525602565
SerlieAlalieAlaAspSerArgThrLeuAlaProliePro
257025752580
GlyTrpSerPheThrThrAlaAlaSerValProValValPhe
258525902595
ThrAlaTyrTyrAlaLeuValAspLeuAlaValLeuGlyAla
260026052610
GluSerValLeulieHisAlaAlaAlaGlyGlyValGlyMet
261526202625
AlaThrGinLeuAlaArgHisLeuGlyAlaGluValPheAla
263026352640
AlaSerAlaGlyLysGinHisValLeuArgArgValGlyLeu
264526502655
AspSerArgValAlaAspSerArgThrThrGluPheArgGlu
266026652670
PheGlyGlyArgValAspValValLeuAsnSerLeuSerGly
267526802685
PheValAspAlaSerLeuAspValLeuSerAspGlyGlyArg
269026952700
ValGluMetGlyLysThrAsplieArgAlaGlySerGlyArg
270527102715
GlyValSerTyrArgAlaPheAspLeuLeuGluAlaGlyPro
272027252730
ArgLeuArgGlulieLeuAlaGluLeuLeuThrLeuPheGlu
273527402745
GlyValLeuGinProLeuProValArgAlaTrpAsplieArg
275027552760
AlaArgGluAlaPheSerTrpMetSerArgAlaArgHisVal
276527702775
LyslieValLeuThrValProArgArgLeuAspGlyAspGly
278027852790
Val Glu Phe Gly Glu Ala Gly Ala Thr Asp Lys Glu Phe Pro Glu Arg Gin Gly Thr
ValLeulieThrGlyGlySerGlyValLeuAlaGlylieVal
279528002805
ArgHisLeuValArgGluTyrAspAlaArgHisLeuLeuLeu
281028152820
SerArgSerAlaProAspGluGlyLeuLeuAlaGluLeuGly
282528302835
ArgAlaGluValValLeuCysAspValSerAspArgThrAla
284028452850
GluSerValLeuSerGlyArgThrLeuThrAlaVallieHis
285528602865
AlaGlyAlaLeuAspAspGlyValValGluAlaGlnThrPro
287028752880
ArglieAspSerValPheArgProLysValAspGlyAlaTrp
288528902895
LeuHisGluLeuThrArgAsnMetAspLeuAlaAlaPhelie
290029052910
TyrSerSerAlaAlaGlylieMetGlySerAlaGlyGlnGly
291529202925
TyrAlaAlaAlaAsnAlaPheValAspAlaLeuAlaValGln
293029352940
GlnHisGluGlyLeuProGlyLeuAlaLeuAlaTrpGlyLeu
294529502955
AlaAspAlaSerGlyLeuThrAlaGlnLeuThrAspAlaAsp
296029652970
AspArglieArgArgAlaGlyGlnArgThrlieSerAlaGlu
297529802985
GlyMetArgLeuPheAspGlyAlaLeuArgHisGlyGluPro
299029953000
LeuValThrAlaAlaLeuAspProValArgGluGlyGlulie
300530103015
ProLeuLeuArgSerLeuHisArgProValValArgArgAla
302030253030
ProAlaGlyGlyGluSerSerGlnHisTrpLeuValArgLeu
303530403045
ProAlaGluArgGluAlaAlaLeuLeuLysAlaValSerGlu
305030553060
AlaAlaThrValLeuGlyHisAlaAspAlaArgSerliePro
306530703075
SerAlaValPheArgAspLeuGlyMetAspSerLeuThrAla
308030853090
GluLeuArgAsnAsnLeuAlaLysThrThrGlyLeuArgLeu
309531003105
AlaThrMetAlaPheAspTyrProThrProThrAlaLeuAla
311031153120
ArgLeuAspGluLeuLeuThrGlyGluThrProAlaProAla
312531303135
LysSerGluAlaProThrSerThrAlaThrAspGluProLeu
314031453150
lieValGlyMetAlaCysArgLeuProGlyGlyValSerSer
315531603165
GluGluLeuTrpArgLeuValValSerGlyGlyAspAlalie
317031753180
AspPheProValAspArgGlyTrpAspValSerGlyLeuArg
318531903195
GlyPheLeuAlaGlyAlaAlaAspPheAspAlaAlaPhePhe
320032053210
lieSerProArgGluAlaLeuAlaMetAspProGinGinArg
321532203225
ValLeuGluThrSerTrpGluAlaLeuGluArgAlaGlylie
323032353240
ProAspSerLeuArgGlySerAspThrGlyValPheMetGly
324532503255
TyrProGlyGlyTyrGlyValGlyAlaAspLeuGlyGlyPhe
326032653270
AlaThrAlaGlyAlaValSerValLeuSerGlyArgValSer
327532803285
PhePheGlyPheGluGlyProAlaMetThrValAspThrAla
329032953300
SerSerSerLeuValAlaLeuHisGinAlaGlyTyrAlaLeu
330533103315
GinGlyGluCysSerlieAlaLeuValGlyGlyValThrVal
332033253330
AlaThrProGinThrPheValGluPheAlaArgGinGlyGly
333533403345
AlaAlaAspGlyArgSerLysAlaPheAlaAspSerAlaAsp
335033553360
AlaGlyPheSerGluGlyValGlyValLeuValValGluArg
336533703375
Pro Ser Val Ala Pro Ser Gly Gly Val Arg Ala Gly Tyr Cys Arg Met Leu Gly Leu
SerAspAlaGlnAlaLysAsnHisGlnlieLeuAlaValVal
338033853390
GlySerAlaValAsnGlnAspGlyAlaSerAsnGlyLeuThr
339534003405
ProAsnGlyProSerGlnGlnArgVallieArgGlnAlaLeu
341034153420
AsnAlaSerLeuAsnProAlaAspValAspValValGluAla
342534303435
GlyThrGlyThrThrLeuGlyAspProlieGluAlaGlnAla
344034453450
LeuAlaThrTyrGlyGlnGlyArgAlaValProLeuLeuLeu
345534603465
SerValLysSerAsnValGlyHisThrGlnAlaAlaAlaGly
347034753480
AlaGlyVallieLysMetValLeuAlaLeuGlnHisGlyVal
348534903495
ProGlnThrLeuHisValAspGluProSerArgHisValAsp
350035053510
SerAlaGlySerValGluLeuAlaThrSerAsnArgSerLeu
351535203525
SerPheAspArgProTrpArgAlaGlyValSerSerPheGly
353035353540
SerGlyThrAsnAlaHisVallieLeuGluAlaAlaProAla
354535503555
AlaProAlaPheAspProAspSerThrSerGlyAlaThrGly
356035653570
AlaGlyAlaAlaAlaLeuProLeuAlalieSerAlaArgSer
357535803585
SerAlaLeuAlaAspLeuThrThrArgLeuArgAlaTyrLeu
359035953600
AlaAsnProAspThrAspLeuHisThrThrAlaThrThrLeu
360536103615
ThrThrArgSerSerPheAspHisArgAlaValLeuLeuGly
362036253630
AspThrlieThrGlyThrAlaAlaValAspProArgValVal
363536403645
ValPheSerGlyGlnGlySerGlnArgAlaGlyMetGlyAla
365036553660
LeuAlaAlaAlaPheProValPheAlaAsplieHisGlnArg
Arg Ala Ala His Leu Gly Val Val Trp Pro lie Pro Leu Glu Thr Ala Asp Phe Glu Val
30
366536703675
TrpGlyLeuLeuAsnValAspGluAspLeuAsnValAspAsp
368036853690
GlyTyrAlaGinProAlaLeuPheAlaLeuGinValAlaLeu
369537003705
GlyLeuLeuGluSerTrpGlyValArgProAspAlaLeulie
371037153720
HisSerlieGlyGluLeuAlaAlaAlaTyrValAlaGlyVal
372537303735
SerLeuGluAspAlaCysThrLeuValSerAlaArgAlaArg
374037453750
MetGinAlaLeuProSerGlyGlyValMetValAlaValPro
375537603765
SerGluAspGluAlaArgThrValLeuArgAspGlyValGlu
377037753780
AlaAlaValAsnGlyProSerSerValValLeuSerGlyAsp
378537903795
AspAlaValLeuGinAlaValAlaGlyPheProArgTrpThr
380038053810
LeuSerThrSerHisAlaPheHisSerAlaArgMetAsnPro
381538203825
LeuGluGluPheArgAlaValAlaGluGinLeuThrTyrHis
383038353840
ProSerValGluMetAlaAlaGlyGluGinValValThrPro
384538503855
TyrTrpValArgGinValArgAspAlaValArgPheGlyGlu
386038653870
ValAlaAlaTyrGluAspAlaValPheValGlulieGlyPro
387538803885
ArgAsnLeuAlaArgLeulieAspGlyValAlaMetLeuAsn
389038953900
GluAsnGluThrHisAlaAlaLeuThrGlyLeuSerGinLeu
390539103915
ValArgGlylieMetProAspTrpSerAlaValLeuGlyVal
392039253930
ThrGlyArgValLeuAspLeuProThrTyrProPheGinHis
393539403945
ArgTyrTrpLeuArgGlyAlaAspArgValGluGlyHisPro
395039553960
Thr Phe Gly Trp Leu Val lie Glu Arg Met Gin Glu Gin Gly Gly Phe Ser Glu Leu0999]LeuGlyLeuProValArgLeuAlaSerSerAspGluValVal1000]3965397039751001]ThrAlaLysliePheArgAspSerAspGlnTrpLeuArgAsp1002]3980398539901003]AlaValLeuProAlaAlaAlaPheValGlulieAlaValSer1004]3995400040051005]AlaAspGluValGlyCysGlyGlnValGluGluLeuValVal1006]4010401540201007]SerLeuProArgLeuProGluAspAlaAlaValGluValGln1008]4025403040351009]TrplieGlyGlyProGluAspGlyGlyArgArgArgLeuThr1010]4040404540501011]TyrGlyArgTyrThrGluThrGluProTrplieProLeuAla1012]4055406040651013]GlylieLeuThrSerGlyProAlaProSerProAspHisAla1014]4070407540801015]ProAlaTrpProProValGlyAlaValProValAspAlaAsp1016]4085409040951017]ProAlaTrpArgArgGlySerGluLeuPheAlaGluValAla1018]4100410541101019]AspGlyGluLeuAspAlaAlaArgPheAlaMetHisProAla1020]4115412041251021]LeuAspAlaAlaValAspValAlaGlyAspGlyValAlaAla1022]4130413541401023]TrpArgGlyLeuThrLeuHisAlaSerLysAlaThrGluLeu1024]4145415041551025]ValHisLeuThrAspHisGlyValValAlaValAspProAla1026]4160416541701027]LeuProValLeuSerAlaGlyAlaLeulieArgArgProLeu1028]4175418041851029]lieArgGluProHisSerSerAspLeuLeuThrValSerTrp1030]4190419542001031]GlulieProAlaProAlaSerSerThrSerAspValAlaGlu1032]4205421042151033]PheThrAlaLeuProAspAspSerThrAspValLeuThrGln1034]4220422542301035]ArgAlaLeuThrSerGlnValLeuThrAlalieGlnSerTrp1036]4235424042451037]AspArgAspAspGlyThrLeuLeulieArgThrGlyMetGly1038]4250425542601039]AlaGlyAlaAlaValSerGlyLeuValArgSerAlaGinSer1040]4265427042751041]HisProGlyArgPheValLeuValGluSerAspAspAspVal1042]4280428542901043]GlyProAlaLeuAspSerProAlaSerProGlySerSerVal1044]4295430043051045]ProGlySerProAlaSerLeuAlaSerLeuAspGluProArg1046]4310431543201047]ArgMetThrGlyGlyArglieGluValProArgLeuThrArg1048]4325433043351049]SerSerGluProAlaGlyGluAlaValTrpAspProGluGly1050]4340434543501051]ValVallieThrGlyGlySerGlyValLeuAlaGlylieLeu1052]4355436043651053]ArgHisLeuValAsnGluArgGlyMetArgArgLeuLeuLeu1054]4370437543801055]SerArgGlyAlaProAspGluAlaLeuLeuThrGluLeuGly1056]4385439043951057]ArgAlaGluAlaAlaValCysAspValSerAspArgAlaAla1058]4400440544101059]GluArgValLeuAlaGlyArgArgLeuThrAlaValValHis1060]4415442044251061]AlaGlyVallieAspAspGlyVallieGluSerMetliePro1062]4430443544401063]ArglieAspAlaValLeuArgAlaLysValAspGlyAlaTrp1064]4445445044551065]LeuHisGluLeuThrArgGluGinGluLeuAlaAlaPheVal1066]4460446544701067]TyrSerSerAlaAlaGlyValLeuGlySerAlaGlyGinGly1068]4475448044851069]TyrAlaAlaAlaAsnAlaPheValAspAlaLeuAlaGluArg1070]4490449545001071]ArgAlaGluGlyLeuProGlyLeuAlaValAlaTrpGlyLeu1072]4505451045151073]GluAspSerSerGlyLeuThrAlaGinLeuSerAspAlaAsp1074]4520452545301075]GluArgMetArgArgSerGlyPheThrSerlieThrAlaGlu1076]453545404545
Glu Asp Trp Leu Val Thr Ala Leu Asp Leu Thr Glu His Val Asn Arg Trp Arg His
331077]GlyMetArgLeuLeuAspMetAlaLeuArgHisArgGluProAla1078]4550455545601079]ValValAlaAlaProThrThrAlaValGlyAspGlyGluValPro1080]4565457045751081]AlaLeuLeuArgSerLeuHisArgThrGlySerArgArgLysAla1082]4580458545901083]SerThrGlyAlaGlyGinTrpLeuValGlyLeuSerProValGlu1084]4595460046051085]ArgGluArgAlaLeuLeuThrAlaValArgAspAsnAlaAlaVal1086]4610461546201087]ValLeuGlyHisHisGlyAlaArgAlalieProAlaAsnAlaAla1088]4625463046351089]PheArgAspLeuGlyMetAspSerLeuThrAlaValGluLeuArg1090]4640464546501091]AsnSerLeuAlaLysThrThrGlyLeuArgLeuProAlaThrLeu1092]4655466046651093]ValPheAspTyrProThrProAlaAlaLeuAlaAlaArgLeuAsp1094]4670467546801095]GluLeuLeuValGlyArgAlaAlaAlaProAlaArgArgAlaAla1096]4685469046951097]SerAlaValGlyGinAspGluProLeuAlalieValGlyMetAla1098]4700470547101099]CysArgLeuProGlyGlyValSerSerProGluAspLeuTrpArg1100]4715472047251101]LeuValGluSerGlyThrAspAlalieSerGlyPheProThrAsp1102]4730473547401103]ArgGlyTrpAspValGluAsnLeuPheAspProAspProAspAla1104]4745475047551105]AlaGlyLysThrTyrCysValGinGlyGlyPheLeuAspThrAla1106]4760476547701107]AlaGluPheAspAlaGlyPhePheGlylieSerProArgGluAla1108]4775478047851109]LeuAlaMetAspProGinGinArgLeuValLeuGluAlaSerTrp1110]4790479548001111]GluAlaPheGluArgAlaGlylieAspProGlySerMetArgGly1112]4805481048151113]SerAspThrGlyValPhelieGlyAlaTyrProGlyGlyTyrGly1114]4820482548301115]ValGlyValGluPheGlyGlyLeuGlyAlaThrAlaGlyAlaGly1116]4835484048451117]SerValLeuSerGlyArgValSerTyrPhePheGlyLeuGlu1118]4850485548601119]ProAlaMetThrValAspThrAlaCysSerSerSerLeuVal1120]4865487048751121]LeuHisGlnAlaGlyTyrAlaLeuArgGlnGlyAspCysSer1122]4880488548901123]AlaLeuValGlyGlyValThrValMetSerThrProHislie1124]4895490049051125]ValGluPheSerArgGlnArgGlyLeuSerValAspGlyArg1126]4910491549201127]LysAlaPheGlyAspGlyAlaAspGlyThrGlyTrpAlaGlu1128]4925493049351129]ValGlyValLeuLeuValGluArgLeuSerAspAlaArgArg1130]4940494549501131]GlyHisArgValLeuAlaValValLysGlySerAlaValAsn1132]4955496049651133]AspGlyAlaSerAsnGlyLeuThrAlaProAsnGlyProSer1134]4970497549801135]GlnArgVallieGluAlaAlaLeuAlaSerAlaGlyLeuSer1136]4985499049951137]AlaAspValAspValValGluAlaHisGlyThrGlyThrThr1138]5000500550101139]GlyAspProlieGluAlaGlnAlaValLeuAlaThrTyrGly1140]5015502050251141]GlyArgSerThrProLeuLeuLeuGlySerLeuLysSerAsn1142]5030503550401143]GlyHisThrGlnAlaAlaAlaGlyValAlaGlyVallieLys1144]5045505050551145]ValMetAlaLeuGlnHisGlyValValProGlnThrLeuHis1146]5060506550701147]AspValProSerArgHisValAspTrpSerAlaGlyAlaVal1148]5075508050851149]ValValThrSerAsnGlnProTrpProSerSerGlyArgPro1150]5090509551001151]ArgAlaGlyValSerAlaPheGlyValSerGlyThrAsnAla1152]5105511051151153]VallieLeuGluSerAlaProAspGluProValSerGluVal1154]512051255130
Gly Ala Leu Phe Cys Gly Asn Gln Gln Ala Leu Gln Ile Met Ile Asp Gly His Ala1155]GlyProAlaProValValAlaAspValValProLeuValLeuSer1156]5135514051451157]AlaArgThrValProAlaLeuGlyGluLeuGluAlaArgValArg1158]5150515551601159]AlaTyrValAlaAlaAlaGluAspAspArgAlaValAlaAlaThr1160]5165517051751161]LeuAlaTrpSerArgAlaValPheGluHisArgAlaValLeulie1162]5180518551901163]GlyGluAspThrlieThrGlyValAlaAlaValAspProArgVal1164]5195520052051165]ValPheValPheProGlyGinGlyTrpGinTrpLeuGlyMetGly1166]5210521552201167]ValGinLeuArgAspSerSerValValPheAlaSerArgMetAla1168]5225523052351169]GluCysAlaAlaAlaLeuSerGluPheValAspTrpAspLeuPhe1170]5240524552501171]AlaAlaLeuAspAspProAlaValValAspArgValAspValVal1172]5255526052651173]GinProValCysTrpAlaValMetValSerLeuAlaAlaValTrp1174]5270527552801175]GinAlaAlaGlyValThrProAspAlaValValGlyHisSerGin1176]5285529052951177]GlyGlulieAlaAlaAlaValValAlaGlySerLeuSerLeuArg1178]5300530553101179]AspGlyAlaArgValValAlaGinArgSerGinLeulieAlaGin1180]5315532053251181]GlyLeuAlaGlyHisGlyAlaMetAlaSerlieAlaLeuProAla1182]5330533553401183]AspGlulieThrLeuValAspGlyAlaTrplieAlaAlaLeuAsn1184]5345535053551185]GlyProAlaSerThrVallieAlaGlyThrProGluAlaValGlu1186]5360536553701187]AlaValLeuAlaAlaGinAspAlaArgValArgArglieAlaVal1188]5375538053851189]AspTyrAlaSerHisThrProGinValGluAlalieArgAspGlu1190]5390539554001191]LeuLeuAlaLeuThrAlaAspValAspSerGinAlaProAlaVal1192]5405541054151193]ProTrpLeuSerThrValAspGlyAlaTrpValAspGlyProLeu1194]5420542554301195]SerValAspTyrTrpPheArgAsnLeuArgGluGlnValGly1196]5435544054451197]AlaGlnAlaValGlnThrLeuGlyAspAlaValPheValGlu1198]5450545554601199]SerAlaSerProValLeuMetGlnSerMetValAspAlaVal1200]5465547054751201]ValProThrLeuArgArgAspAspGlySerProAlaArgLeu1202]5480548554901203]ThrSerLeuAlaGluAlaPheValGlnGlyValAspValAsp1204]5495550055051205]AlaAlaValLeuGlyAlaGlyAlaGluArgAlaLeuAspLeu1206]5510551555201207]ThrTyrProPheAspArgGlnArgTyrTrpValValAlaAsp1208]5525553055351209]ValSerGlyAspValSerGlyAlaGlyLeuGlyThrValGlu1210]5540554555501211]ProLeuLeuGlyAlaValValAlaLeuProGlySerAspGly1212]5555556055651213]ValLeuThrGlyArgValSerLeuAlaThrHisGlyTrpLeu1214]5570557555801215]AspHisAlaValArgGlySerValLeuMetProGlyThrGly1216]5585559055951217]ValGluLeuValValArgAlaAlaAspGluValGlyCysAsp1218]5600560556101219]ValAspGluLeuValSerGluAlaProLeulieValProAla1220]5615562056251221]GlyGlyValGlnLeuSerLeuAlaValGlyGluAlaAspGlu1222]5630563556401223]GlyArgArgGlnValThrLeuPheSerArgAlaAspAspAla1224]5645565056551225]GluTrpValArgHisValThrAlaThrlieSerAlaSerGly1226]5660566556701227]AlaLeuAlaThrProLeuLeuAlaGluTrpProProAlaGly1228]5675568056851229]GluSerValAspValThrGlyPheTyrGluArgLeuAlaAla1230]5690569557001231]GlyHisGluTyrGlyProAlaPheGlnGlyLeuGlnValAla1232]570557105715
Phe Val Thr Val Trp Pro Arg His Leu Ala Phe Val Ala Gly Asp Ala Ala Ala Trp1233]ArgAlaGlyAspThrValTyrAlaGluValAlaLeuAlaGluGlu1234]5720572557301235]GinGluArgGluAlaAlaArgTyrAlaValHisProAlaLeuLeu1236]5735574057451237]AspAlaAlaLeuHisAlaGlyMetValSerGlyPheGinAlaAsp1238]5750575557601239]GlyThrValArgLeuProPheThrTrpAsnAsnValArgValGin1240]5765577057751241]GlyThrGlyProLysArgLeuArgValAlaThrThrArgGlySer1242]5780578557901243]LeuGinLeuAlaAspGluGinGlyArgProValAlaGlylieGly1244]5795580058051245]SerLeuValThrArgArglieAlaAspAspAsnGinLeuLeuThr1246]5810581558201247]ValThrTrpThrGluValThrAlaGlyAlaProValAsnAspAla1248]5825583058351249]GluValPheThrAlaLeuProGlyAsnSerAlaAspValLeuAla1250]5840584558501251]GlulieArgThrLeuThrGluArgPheSerGluAlalieGinAla1252]5855586058651253]TrpLeuValArgAspAspGlyThrLeulieValArgThrGlyThr1254]5870587558801255]GlyLeuProSerAlaAlalieSerGlyLeuValArgSerAlaGin1256]5885589058951257]SerGluTyrProGlyArgPheValLeuValGluSerAspAspGlu1258]5900590559101259]ThrLeuProAspLeuThrAlaLeuValSerLeuAspGluProGin1260]5915592059251261]LeuArglieAsnAspGlyArglieGluValProArgLeuThrArg1262]5930593559401263]ValThrAlaGluProValGluGinThrAlaTrpAspProAspGly1264]5945595059551265]ThrValLeulieThrGlyAspGinAlaGlyHisValAlaArgHis1266]5960596559701267]LeuValThrGlyArgGlyMetArgAsnLeuLeuLeuLeuProThr1268]5975598059851269]GlyAlaProAspGluThrLeuValAspGluLeuThrLysLeuGly1270]5990599560001271]AlaLysValGluValAlaAlaCysAspLeuThrAspArgAlaAla1272]6005601060151273]LeuAlaGluValLeuAlaAspAlaProAlaLeuThrValVal1274]6020602560301275]HisThrAlaGlyAlaProAspGlyAspThrThrSerLeulie1276]6035604060451277]SerSerTrpHisLeuHisGluLeuThrArgAspArgGlyLeu1278]6050605560601279]AlaPhelieLeuTyrSerSerValAspGlyLeuMetGlyAla1280]6065607060751281]ArgArgSerSerTyrAlaPheValAspAlaLeuAlaValHis1282]6080608560901283]ArgAspGluGlyLeuProGlyLeuSerLeuAlaTrpGlyGlu1284]6095610061051285]SerAlaGluAspAlaMetArgAlaPheAspSerAlaThrArg1286]6110611561201287]SerLeuProLeuValValAlaGlyAlaValThrSerAlaArg1288]6125613061351289]GlyGlulieProAlaLeuLeuArgSerLeuArgArgProLeu1290]6140614561501291]ArgArgThrGlyProAlaAlaGlyAspSerProLeuAlaAla1292]6155616061651293]ProProAlaGluArgGluLysAlaLeuValArgValValCys1294]6170617561801295]SerAlaAlaAlaValLeuGlyHisAlaAspThrArgAlaVal1296]6185619061951297]AlaThrAlaAlaPheLysAspLeuGlyLeuAspSerLeuThr1298]6200620562101299]ValAspLeuArgAsnSerLeuGlyLysAlaThrGlyLeuGln1300]6215622062251301]ProAlaThrLeuValPheAspTyrProThrProThrAlaLeu1302]6230623562401303]AlaArgLeuAlaGluLeuLeuThrGlyGluSerAlaThrPro1304]6245625062551305]ArgLysSerAlaValSerAlaSerLeuAspGluProLeuAla1306]6260626562701307]ValGlyMetAlaCysArgLeuProGlyGlyValAlaSerPro1308]6275628062851309]AspLeuTrpArgLeuValGluSerGlyThrAspAlalieSer1310]629062956300
391311]PheProAlaAspArgGlyTrpAspValAspGlyLeuPheAsp1312]6305631063151313]AspProAspAlaAlaGlyLysThrTyrCysValGinGlyGly1314]6320632563301315]LeuAspAlaAlaGlyGluPheAspAlaGlyPhePheGlylie1316]6335634063451317]ProArgGluAlaLeuMetMetAspProGinGinArgValLeu1318]6350635563601319]GluAlaSerTrpGluAlaPheGluArgAlaGlylieGluPro1320]6365637063751321]SerValArgGlySerAspThrGlyValPhelieGlyAlaPhe1322]6380638563901323]ValGlyTyrGlyAlaGlyValAspHisGluGlyTyrThrAla1324]6395640064051325]AlaGlyValGlySerValLeuSerGlyArgLeuSerTyrPhe1326]6410641564201327]GlyLeuGluGlyProAlaMetThrMetAspThrAlaCysSer1328]6425643064351329]SerLeuValAlaLeuHisLeuAlaAlaGinAlaLeuArgAsn1330]6440644564501331]GluCysSerLeuAlaLeuAlaGlyGlyValThrValMetAla1332]6455646064651333]ProGluValPheThrGluPheAlaArgGinArgGlyLeuAla1334]6470647564801335]AspGlyArgCysLysProPheAlaAspAlaAlaAspGlyAla1336]6485649064951337]PheSerGluGlyAlaGlyLeuLeuValValGluArgLeuSer1338]6500650565101339]AlaArgArgAsnGlyHisGinValLeuAlaVallieArgGly1340]6515652065251341]AlaValAsnGinAspGlyAlaSerAsnGlyLeuThrAlaPro1342]6530653565401343]GlyProSerGinGinArgVallieArgGinAlaLeuAlaAsn1344]6545655065551345]GlyLeuSerSerAlaAspValAspValLeuGluAlaHisGly1346]6560656565701347]GlyThrThrLeuGlyAspProlieGluAlaGinAlaValLeu1348]6575658065851349]ThrTyrGlyGinAspArgSerAlaProLeuLeuMetGlySer
Pro Phe Ser Leu Thr Pro Thr Phe Ser Gly Thr Ala Gly Asp Ser Asn Ala Thr Ala Leu1350]6590659566001351]LysSerAsnlieGlyHisThrGlnAlaAlaSerGlyValAla1352]6605661066151353]ValIleLysMetValMetAlaLeuArgHisGlyValValPro1354]6620662566301355]SerLeuHisValAspGluLeuSerArgHisValAspTrpSer1356]6635664066451357]GlyAlaValAspValValThrSerAsnGlnProTrpProSer1358]6650665566601359]AspArgProArgArgAlaGlyValSerAlaPheGlyValSer1360]6665667066751361]ThrAsnValHisVallieLeuGluSerAlaProValGluSer1362]6680668566901363]AlaGluValAlaGlyAlaAlaProValValAlaAspValVal1364]6695670067051365]LeuValLeuSerAlaArgSerAlaProAlaLeuSerValLeu1366]6710671567201367]AlaArgValArgAlaTyrValAlaAlaAlaGluAsnGluArg1368]6725673067351369]ValAlaAlaThrLeuAlaSerSerArgAlaValPheGluHis1370]6740674567501371]AlaValLeulieGlyAspAspSerValValGlyAlaAlaAla1372]6755676067651373]AspProArgValValPheValPheProGlyGlnGlyTrpGln1374]6770677567801375]LeuGlyMetGlyValGlnLeuArgAspSerSerValValPhe1376]6785679067951377]SerArgMetAlaGluCysAlaAlaAlaLeuSerGluPheVal1378]6800680568101379]TrpAspLeuPheAlaAlaLeuAspAspProAlaValValAsp1380]6815682068251381]ValAspValValGlnProValCysTrpAlaValMetValSer1382]6830683568401383]AlaAlaValTrpGlnAlaAlaGlyValGlyProAspAlaVal1384]6845685068551385]GlyHisSerGlnGlyGlulieAlaAlaAlaValValAlaGly1386]6860686568701387]LeuSerLeuArgAspGlyAlaArgValValAlaGlnArgSer1388]687568806885
Gly Gln Ala Ser Gly Val Pro Glu Ala Arg Val Trp Ala Asp Arg Leu Val Ser Gln1389]LeulieAlaArgGlyLeuAlaGlyHisGlyAlaMetAlaSerlie1390]6890689569001391]AlaLeuProAlaAspGlulieThrLeuValGluGlyAlaTrpVal1392]6905691069151393]AlaAlaLeuAsnGlyProAlaSerThrVallieAlaGlyThrPro1394]6920692569301395]AspAlaValGluAlaValLeuAlaAlaGinAspAlaArgValArg1396]6935694069451397]ArglieAlaValAspTyrAlaSerHisThrProGinValGluAla1398]6950695569601399]lieArgAspGluLeuLeuAlaLeuThrAlaAspValAspSerGin1400]6965697069751401]AlaProAlaValProTrpLeuSerThrValAspGlyAlaTrpVal1402]6980698569901403]AspGlyProLeuSerValAspTyrTrpPheArgAsnLeuArgGlu1404]6995700070051405]GinValGlyPheAlaGinAlaValGinThrLeuGlyAspAlaVal1406]7010701570201407]PheValGluValSerAlaSerProValLeuMetGinSerMetVal1408]7025703070351409]AspAlaValThrValAlaThrLeuArgArgAspAspGlySerAla1410]7040704570501411]ThrArgLeuValSerSerLeuAlaGluAlaPheValGinGlyVal1412]7055706070651413]AspValAspTrpThrAlaValLeuGlyAlaGlyGlyValArgVal1414]7070707570801415]LeuAspLeuProThrTyrProPheGinArgGinHisPheTrpAla1416]7085709070951417]LeuProAspGinThrAlaGlyAspValSerGlyAlaGlyLeuAsp1418]7100710571101419]AlaValArgHisProLeuLeuGlyAlaValValAlaLeuProGly1420]7115712071251421]SerAspGlyLeuValLeuThrGlyArgValSerLeuAlaThrHis1422]7130713571401423]AlaTrpLeuAlaAspHisAlaValArgGlySerValLeuMetPro1424]7145715071551425]GlyThrGlyPheValGluLeuValValArgAlaAlaAspGluVal1426]7160716571701427]GlyCysAspValValAspGluLeuVallieGluAlaProLeuArg1428]7175718071851429]LeuProThrAlaGlyGlyValGlnLeuSerValSerValGly1430]7190719572001431]AlaAspGluGlyGlyArgArgGlnValThrValHisSerArg1432]7205721072151433]AspAlaAlaGluThrTrpThrArgHisValThrAlaThrVal1434]7220722572301435]AsnAlaGluAlaSerGlyProProProAspLeuArgGlnTrp1436]7235724072451437]ProAlaAsnGlyThrProValAspValSerGlyPheTyrAsp1438]7250725572601439]LeuGlyGlyTyrGluTyrGlyProAlaPheGlnGlyLeuArg1440]7265727072751441]AlaTrpLysValGlyGluThrlieTyrAlaGluValAlaLeu1442]7280728572901443]GluGluGlnArgAlaGluAlaAlaArgPheGlyValHisPro1444]7295730073051445]LeuLeuAspAlaAlaLeuHisAlalieMetLeuGlySerAla1446]7310731573201447]GlyAspGlySerValGlnLeuProPheSerTrpSerGlyVal1448]7325733073351449]ValHisAlaAlaGlyAlaAlaAlaLeuArgValValValAsp1450]7340734573501451]GlySerLeuArgLeuAlaAspGluSerGlyArgProValAla1452]7355736073651453]ValAspAlaLeuValThrArgProMetAlaAspAspValAla1454]7370737573801455]AspLeuLeuAlaValSerTrpThrGlulieAlaAlaGlyPro1456]7385739073951457]GlyAspAspValGluValPheThrAlaLeuProGlyAspGly1458]7400740574101459]ValLeuAlaGluSerArgGlyLeuThrGlyArgValLeuAla1460]7415742074251461]lieGlnAlaTrpLeuGlyArgAspAspGlyThrLeuVallie1462]7430743574401463]ThrGlyThrGlyLeuAlaSerAlaAlaValSerGlyLeuVal1464]7445745074551465]SerAlaGlnSerGluHisProGlyArgPheValLeuValGlu1466]746074657470
Glu Thr Ser Pro Ala Ala Ala Ala Glu Arg Arg Thr Asp Val Asp Ala Arg Arg Ser1467]AspAspValValThrAlaGlyGinLeuSerSerValAlaGlyLeu1468]7475748074851469]AspGluProArgLeuArglieValAspGlyArgValGluValPro1470]7490749575001471]ArgLeuThrArgValValAlaGluProValGluAlaProGlyTrp1472]7505751075151473]AspProAspGlyThrValLeulieThrGlyGlySerGlyValLeu1474]7520752575301475]AlaGlylieValAlaArgHisValValAlaGluArgGlyValArg1476]7535754075451477]ArgValLeuLeuLeuSerArgThrAlaProAspGluValLeuVal1478]7550755575601479]AlaAspLeuThrAspLeuGlyAlaGluValAspValAlaArgCys1480]7565757075751481]AspValSerAspArgAlaAlaLeuAlaGluValLeuAlaGlyVal1482]7580758575901483]ProValLeuThrAlaVallle His Thr Ala Gly Val Leu Asp Asp1484]7595760076051485]GlyVallieGluSerLeuThrProGluArgLeuAspGlyValPhe1486]7610761576201487]ArgProLysValAspGlyAlaTrpHisLeuHisGluLeuThrArg1488]7625763076351489]AspArgAspLeuAlaAlaPheValValTyrSerSerAlaAlaGly1490]7640764576501491]ValLeuGlySerAlaGlyGinGlyAsnTyrAlaAlaAlaAsnAla1492]7655766076651493]PheLeuAspAlaLeuAlaValGinArgArgLeuGluGlyLeuPro1494]7670767576801495]GlyLeuAlaLeuAlaTrpGlyLeuTrpAlaAspAlaSerGlyLeu1496]7685769076951497]ThrAlaThrMetThrAspAlaAspArgAspArglieArgArgGly1498]7700770577101499]GlyLeuArgAlalieThrAlaGluTyrGlyMetArgLeuPheAsp1500]7715772077251501]ThrAlaMetHisArgGluGluProMetLeulieAlaAlaAlalie1502]7730773577401503]GlyThrProArgAspGlyGinValProAlaLeuLeuArgSerLeu1504]7745775077551505]HisArgProValAlaArgArgSerAlaAlaProArgAspSerSer[1506776077657770[1507Ala Gln TrpLeuAlaThrLeuAlaProGluGluArgAspAlaAla[1508777577807785[1509Leu Leu GlnLeuValCysAspSerAlaAlaValValLeuGlyHis[1510779077957800[1511Gly Asp GlySerAlalieProValThrAlaThrPheLysAspLeu[1512780578107815[1513Gly Val AspSerLeuThrAlaValGluValArgAsnArgLeuAla[1514782078257830[1515Ala Ala ThrGlyLeuArgLeuProAlaThrMetValPheAspTyr[1516783578407845[1517Pro Thr ProGlyValLeuAlaAlaHisLeuGlyValLeuPheAla[1518785078557860[1519Pro Pro GluProGluProAsnAsplieGlnGluArgGluLeuArg[1520786578707875[1521Arg Ala LeuAlaAlalieSerValAlaLysPheArgGluAlaGly[1522788078857890[1523Val Leu AspThrLeuLeuArgLeuAlaAlaGlyGluThrLysPro[1524789579007905[1525Asp Thr GlyGlyAspSerGlyAspAspGluAlaLeuValAspGlu[1526791079157920[1527Met Asp AlaAspAlaLeulieLysHisValLeuGluAlaGlyArg[1528792579307935[1529<210>3[1530<211>19[1531<212>DNA[1532<213>引物[1533<400>3[1534tsaagtcsaa catcggbca[1535<210>4[1536<211>20[1537<212>DNA[1538<213>引物[1539<400>4[1540cgcaggttsc sgtaccagta[1541<210>5[1542<211>403[1543<212>PRT[1544<213>Actinoplanes
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451545]<400>51546]LysSerAsnlieGlyHisThrGinAlaAlaAlaGlyValAlaGlyVal1547]1510151548]lieLysMetValMetAlaLeuArgHisGlyValValProArgSerLeu1549]2025301550]HisValAspValProSerArgHisValAspTrpSerAlaGlyAlaVal1551]3540451552]AspValValThrSerAsnGinProTrpProSerSerAspArgProGly1553]5055601554]ArgAlaGlyValSerAlaPheGlyValSerGlyThrAsnAlaHisVal1555]657075801556]lieLeuGluSerAlaProPheGluProAlaAspGinlieAlaGlyPro1557]8590951558]ValProValValAlaAspValValProLeuValLeuSerAlaArgThr1559]1001051101560]ValProAlaLeuThrGluLeuGluAlaArgValArgAlaTyrValSer1561]1151201251562]AlaAlaGluAspAspArgAlaValAlaAlaThrLeuAlaSerSerArg1563]1301351401564]AlaValPheGluHisArgAlaValLeulieGlyGluAspThrValAsn1565]1451501551601566]GlySerAlaLeuSerAspProArglieValPheValPheProGlyGin1567]1651701751568]GlyTrpGinTrpLeuGlyMetGlyValAlaLeuArgAspSerSerVal1569]1801851901570]ValPheAlaSerArgMetAlaGluCysAlaAlaAlaLeuSerGluPhe1571]1952002051572]ValAspTrpAspLeuPheAlaAlaLeuAspAspProAlaValValAsp1573]2102152201574]ArgValAspValValGinProValCysTrpAlaValMetValSerLeu1575]2252302352401576]AlaAlaValTrpGinAlaAlaGlyValThrProAspAlaValValGly1577]2452502551578]HisSerGinGlyGlulieAlaAlaAlaValValAlaGlySerLeuSer1579]2602652701580]LeuArgAspGlyAlaArgValValAlaGinArgSerGinLeulieAla1581]2752802851582]GinGlyLeuAlaGlyHisGlyAlaMetAlaSerlieAlaLeuProAla1583]2902953001584]AspGlulieThrLeuValAspGlyAlaTrpValAlaAlaLeuAsnGly1585]3053103153201586]ProAlaSerThrVallieAlaGlyThrProGluAlaValGluThrVal1587]3253303351588]LeuAlaAlaGlnAspAlaArgValArgArglieAlaValAspTyrAla1589]3403453501590]SerHisThrProGlnValGluAlalieArgAspGluLeuLeuAlaLeu1591]3553603651592]ThrAlaAspValAspSerGlnAlaProAlaValSerTrpLeuSerThr1593]3703753801594]ValAspGlyThrTrpValAspSerProLeuSerValAspTyrTrpTyr1595]3853903954001596]ArgAsnLeu1597]<210>61598]<211>4121599]<212>PRT1600]<213>Streptomyces hygroscopicus1601]<400>61602]LysSerAsnlieGlyHisAlaGlnAlaAlaAlaGlyValSerGlyVal1603]1510151604]IleLysMetValMetAlaLeuArgHisGlyPheValProArgThrLeu1605]2025301606]HisValAspGluProSerArgHisValAspTrpSerAlaGlyAlaVal1607]3540451608]GluLeuValAlaGluAsnArgSerTrpProAlaThrGlyArgProArg1609]5055601610]ArgAlaGlyValSerAlaPheGlyValSerGlyThrAsnAlaHisVal1611]657075801612]lieLeuGluGlyAlaProAlaGlnSerValAspAspAlaAlaGlySer1613]8590951614]ThrProValValAspSerGluLeuValProLeuValValSerAlaLys1615]1001051101616]SerLeuProAlaLeuAlaGluValGluGlyArgLeuArgAlaTyrLeu1617]1151201251618]AlaAlaSerProGlyAlaAspValArgAlaValGlySerThrLeuAla1619]1301351401620]ValThrArgSerLeuPheGluHisArgAlaValLeuLeuGlyAspAsp1621]1451501551601622]SerValThrGlyThrGlyThrAlaValSerAspProArgValValPhe[1623]165170175[1624]ValPheProGlyGinGlyTrpGinTrpLeuGlyMetGlySerAlaLeu[1625]180185190[1626]ArgThrSerSerMetValPheAlaGluArgMetAlaGluCysAlaAla[1627]195200205[1628]AlaLeuSerGluPheValAspTrpAspLeuPheAlaValLeuAspAsp[1629]210215220[1630]ProAlaValValAlaArgValAspValValGinProAlaSerTrpAla[1631]225230235240[1632]ValMetValSerLeuAlaAlaValTrpGinAlaAlaGlyValArgPro[1633]245250255[1634]AspAlaValValGlyHisSerGinGlyGlulieAlaAlaAlaCysVal[1635]260265270[1636]AlaGlyAlaValSerLeuArgAspAlaAlaArgValValThrLeuArg[1637]275280285[1638]SerGinVallieAlaArgGlyLeuAlaGlyArgGlyAlaMetAlaSer[1639]290295300[1640]ValAlaLeuProAlaGinAspValGluLeuValAspGlyAlaTrpVal[1641]305310315320[1642]AlaAlaArgAsnGlyProAlaSerThrValValAlaGlyAlaProGlu[1643]325330335[1644]AlaValAspArgValLeuAlaValHisGluAlaArgGlyValArgVal[1645]340345350[1646]ArgArglieAlaValAspTyrAlaSerHisThrProHisValGluLeu[1647]355360365[1648]lieArgAspGluLeuLeuGlyVallieAlaGlyValAspSerArgAla[1649]370375380[1650]ProValValProTrpLeuSerThrValAspGlyThrTrpValGluGly[1651]385390395400[1652]ProLeuAspAlaGluTyrTrpTyrArgAsnLeuArg[1653]405410[1654]<210>7[1655]<211>8563[1656]<212>PRT[1657]<213>Streptomyces hygroscopicus[1658]<400>7[1659]MetSerArgAlaGluLeu Val ArgProlieTyrAspLeuLeuArgAla[1660]151015[1661]AsnAlaGluArgLeuGly Asp LyslieAlaTyrValAspSerArgLeu
481662]2025301663]AlaLeuThrHisAlaGluLeuAlaThrArgThrGlyArglieAlaGly1664]3540451665]HisLeuValAspMetGlyValAspArgGlyAspArgValAlalieLeu1666]5055601667]LeuGlyAsnArgValGluAsnlieGluSerTyrLeuAlalieAlaArg1668]657075801669]AlaSerAlaValAlaValProLeuAsnProAspAlaThrGluAlaGlu1670]8590951671]ValAlaHisPheLeuSerAspSerGlyAlaValAlaVallieThrAsp1672]1001051101673]SerAlaHisLeuAspAspValArgArgThrAlaProAlaAlaAsnlie1674]1151201251675]ValLeuValGlyGluGluArgThrProProGlyValArgSerPheAla1676]1301351401677]GluLeuAlaThrThrGluProLeuArgProProArgAspAspLeuGly1678]1451501551601679]LeuAspGluProAlaTrpMetLeuTyrThrSerGlyThrThrGlyThr1680]1651701751681]ProLysGlyValLeuSerThrGlnGlySerGlyLeuTrpSerAlaAla1682]1801851901683]TyrCysAsplieProAlaTrpGluLeuThrGluAsnAspValLeuLeu1684]1952002051685]TrpProAlaProLeuPheHisArgLeuAlaLeuHisLeuCysLeuLeu1686]2102152201687]AlaThrThrAlaValGlyAlaThrAlaArglieMetAsnGlyPheVal1688]2252302352401689]AlaSerGluValLeuGluGluLeuThrGluHisArgCysThrValLeu1690]2452502551691]ValGlyValProThrMetSerArgTyrLeuLeuGlyAlaAlaAspThr1692]2602652701693]PheGluProArgThrSerSerLeuLysMetGlyLeuValAlaGlySer1694]2752802851695]ValAlaProAlaSerLeulieGluGlyPheGluAspValPheGlyVal1696]2902953001697]ProLeuLeuAspThrTyrGlyCysThrGluThrSerGlySerLeuThr1698]3053103153201699]ValAsnTrpLeuSerGlyGlnArglieProGlySerCysGlyLeuPro1700]325330335[1701]ValProGly LeuSerLeuArgPheValAspProlieSer GlyAlaAsp[1702]340345350[1703]ValAlaAspGlyGluGluGlyGluLeuTrpAlaSerGlyProSerlie[1704]355360365[1705]MetlieGlyTyrHisGluGinProGluAlaThrAlaGluValLeuSer[1706]370375380[1707]AspGlyTrpTyrArgThrGlyAspLeuAlaArgArgSerGluThrGly[1708]385390395400[1709]HisValThrlieThrGlyArglieLysGluLeulielieArgGlyGly[1710]405410415[1711]GluAsnlieHisProHisGlulieGluAlaValAlaLeuAspValPro[1712]420425430[1713]GlyValLysAspAlaAlaAlaAlaGlyLysGinHisProValLeuGly[1714]435440445[1715]GlulieProValLeuTyrValValProGluThrGlyGlyValAspThr[1716]450455460[1717]AspMetValLeuAlaValCysArgGluArgLeuSerTyrPheLysVal[1718]465470475480[1719]ProGluGlulieTyrArgValAspAlalieProArgThrAlaSerGly[1720]485490495[1721]LysValLysArgSerSerLeuThrGluLysProAlaGluLeuLeuAla[1722]500505510[1723]GlyAlaSerGlyGlyGluThrLeuHisArgLeuGluTrplieProLeu[1724]515520525[1725]AspProProLysGinAlaSerProAspGlyArgHisValValValArg[1726]530535540[1727]ValAspSerLeuProSerAspAlaAlaAspLeuAlaGlyAlaValArg[1728]545550555560[1729]AspLeuAlaGinSerTrpLeuAlaAspLysArgArgAlaAspSerThr[1730]565570575[1731]LeuValPheValThrArgArgAlaValHisThrGlyProSerAspLeu[1732]580585590[1733]ProValProGluHisAlaAlaAlaTrpAspAlalieArgArgGluGin[1734]595600605[1735]ThrGluAsnProGlyValPheValVallieAspValAspPheAspAsp[1736]610615620[1737]AlaAspProAspProAspAspThrLeuLeuArgAlaLeuAlaGlyLeu[1738]625630635640[1739]GlyGluProGinLeuAlaLeuArgAspGlyAsnProLeuValProArg[1740]645650655[1741]LeuAlaHisAlaAsnThrAlaAspSerAspSerLeuThrlieProGlu[1742]660665670[1743]AspArgAlaTrpLeuLeuGluHisSerArgSerGlyThrLeuArgAsp[1744]675680685[1745]LeuAlaLeuValProAlaAspThrAlaGluArgProLeuArgProGly[1746]690695700[1747]GluValArglieAlaValArgAlaAlaGlyLeuAsnPheArgAspVal[1748]705710715720[1749]LeulieAlaLeuGlyThrTyrProGlyGluGlyLeuMetGlyGlyGlu[1750]725730735[1751]AlaAlaGlyValValLeuGluValGlyProGluValHisAspLeuThr[1752]740745750[1753]ProGlyAspArgValPheGlyLeuValGlySerAlaPheGlyGlyVal[1754]755760765[1755]AlalieThrAspArgArgLeuLeuGlyAlalieProAspThrTrpSer[1756]770775780[1757]PheThrThrAlaAlaSerlieProlieValPheAlaThrAlaTyrTyr[1758]785790795800[1759]GlyLeuValAspLeuSerGlyLeuSerAlaGlyGluThrValLeulie[1760]805810815[1761]HisAlaThrAlaGlyGlyValGlyMetAlaAlaThrGlnSerAlaCys[1762]820825830[1763]ArgHisLeuGlyProArglieHisAlaThrAlaSerAlaAlaLysGln[1764]835840845[1765]HislieLeuArgGluAlaGlyLeuGluAspThrArglieAlaAspSer[1766]850855860[1767]ArgThrLeuAlaPheArgGluAlaPheLeuAsnThrThrAspGlyGln[1768]865870875880[1769]GlyValAspValValLeuAsnSerLeuSerGlyAspPheValAspAla[1770]885890895[1771]SerLeuAspLeuLeuProArgGlyGlyArgPheLeuGluMetGlyLys[1772]900905910[1773]ThrAsplieArgAspAlaAspArglieThrAlaAspArgProGlyThr[1774]915920925[1775]ThrTyrGlnAlaPheAspLeuLeuAspAlaGlyProAspArgLeuArg[1776]930935940[1777]GlulielieAlaGluLeuLeuGluLeuPheAlaGlnGlyValLeuArg[1778]9459509559601779]ProLeu Pro Val Leu Thr Trp Asp lie Arg Lys Ala Arg Asp Ala Phe1780]9659709751781]SerTrp Met Ser Arg Ala Arg His Thr Gly Lys lie Thr Phe Thr lie1782]9809859901783]ProArg Arg Leu Asp Pro Asp Gly Thr Val Leu lie Ala Asp Gly Ala1784]995100010051785]GlyAlaLeuThrGlyThrValAlaArgHisLeuValAlaGluGin1786]1010101510201787]GlyValArgHisLeuLeuLeuLeuSerArgSerThrProAspGlu1788]1025103010351789]AlaLeulieAsnGluLeulieGluSerGlyAlaArgValAspThr1790]1040104510501791]AlaValCysAspValSerAspArgAlaGlyLeuValArgThrLeu1792]1055106010651793]AlaGlylieAlaProGluArgProLeuThrAlaVallieHisThr1794]1070107510801795]GlyGlyProAlaValAlaHisGluSerHisGinLeuHisArgLeu1796]1085109010951797]ThrLysGlyLeuAspLeuAlaAlaPheValValPheSerGinAsp1798]1100110511101799]AlaProAlaSerValAspAlaLeuAlaArgSerArgArgAlaGlu1800]1115112011251801]GlyLeuProlieThrAlalieAlaTrpGlylieProGluAlaGlu1802]1130113511401803]AlaValValValArgGlyProLeuLeuGlyArgAlaMetAlaSer1804]1145115011551805]AlaAspSerAlaHislieValThrArgLeuAsnThrValGlyLeu1806]1160116511701807]ArgAlaLeuAlaAlaAlaAspThrLeuProProLeuLeuGinAsn1808]1175118011851809]LeuValGlyAlaHisThrAspThrThrGluGinGinAlaTrpSer1810]1190119512001811]ArgGinPheLeuAlaAlaGluAlaAlaArgGluGinAlaLeuArg1812]1205121012151813]AspLeuValArgSerSerValThrAsplieLeuGlyLeuSerAla1814]1220122512301815]AlaAspArgTyrAlaProAspLysThrSerArgGluMetGlylie1816]1235124012451817]AspSerLeuThrSerValGluLeuArgAsnSerLeuAlaLysAla
521818]1250125512601819]ThrGlyLeuArgLeuProAlaThrLeuValPheAspTyrPro1820]1265127012751821]ProAlaValLeuValValArgLeuGlyGluLeuPheThrGly1822]1280128512901823]SerProAlaProGluArgAlaValSerAlaValGlyGlnGly1824]1295130013051825]ProLeuAlalieValGlyMetAlaCysArgLeuProGlyGly1826]1310131513201827]SerSerProGluAspLeuTrpArgLeuValGluSerGlyThr1828]1325133013351829]AlalieSerGlyPheProThrAspArgGlyTrpAspValAsp1830]1340134513501831]LeuPheAspProAspProAspAlaSerGlyLysSerTyrCys1832]1355136013651833]GlnGlyGlyPheLeuAspThrAlaAlaGlyPheAspAlaSer1834]1370137513801835]PheGlylieSerProArgGluAlaLeuAlaMetAspProGln1836]1385139013951837]ArgLeuValLeuGluValSerTrpGluAlaPheGluArgAla1838]1400140514101839]lieGluProGlySerValArgGlySerAspThrGlyValPhe1840]1415142014251841]GlyGlyPheProGlyGlyTyrGlyAlaGlyAlaAspLeuGlu1842]1430143514401843]PheGlyAlaThrAlaGlyAlaAlaSerValLeuSerGlyArg1844]1445145014551845]SerTyrPhePheGlyLeuGluGlyProAlalieThrValAsp1846]1460146514701847]AlaCysSerSerSerLeuValAlaLeuHisGlnAlaGlyTyr1848]1475148014851849]LeuArgGlnGlyGluCysSerLeuAlaLeuValGlyGlyVal1850]1490149515001851]ValMetProThrProGlnSerPheValGluPheSerArgGln1852]1505151015151853]GlyLeuSerAlaAspGlyArgCysLysAlaTyrAlaAspAla1854]1520152515301855]AspGlyThrGluTrpAlaGluGlyValGlyValLeuLeuVal1856]153515401545
Thr Glu Glu Val Asp Gly Val Phe Gln Gly Met Gly Val Thr Ala Thr Arg Ala Glu1857]ArgLeuSerAspAlaGinAlaLysGlyHisGinValLeuAla1858]1550155515601859]ValArgGlySerAlaValAsnGinAspGlyAlaSerAsnGly1860]1565157015751861]SerAlaProAsnGlyProSerGinGinArgVallieArgAla1862]1580158515901863]LeuSerAsnAlaGlyLeuAlaProHisGluValAspValVal1864]1595160016051865]AlaHisGlyThrGlyThrThrLeuGlyAspProlieGluAla1866]1610161516201867]AlaVallieAlaThrTyrGlyGinAspArgGluGinProVal1868]1625163016351869]LeuGlySerLeuLysSerAsnlieGlyHisAlaGinAlaAla1870]1640164516501871]GlyValSerGlyVallieLysMetValMetAlaLeuArgHis1872]1655166016651873]PheValProArgThrLeuHisValAspGluProSerArgHis1874]1670167516801875]AspTrpSerAlaGlyAlaValGluLeuValAlaGluAsnArg1876]1685169016951877]TrpProAlaThrGlyArgProArgArgAlaGlyValSerAla1878]1700170517101879]GlyValSerGlyThrAsnAlaHisVallieLeuGluGlyAla1880]1715172017251881]AlaGinSerValAspAspAlaAlaGlySerThrProValVal1882]1730173517401883]SerGluLeuValProLeuValValSerAlaLysSerLeuPro1884]1745175017551885]LeuAlaGluValGluGlyArgLeuArgAlaTyrLeuAlaAla1886]1760176517701887]ProGlyAlaAspValArgAlaValGlySerThrLeuAlaVal1888]1775178017851889]ArgSerLeuPheGluHisArgAlaValLeuLeuGlyAspAsp1890]1790179518001891]ValThrGlyThrGlyThrAlaValSerAspProArgValVal1892]1805181018151893]ValPheProGlyGinGlyTrpGinTrpLeuGlyMetGlySer1894]1820182518301895]LeuArgThrSerSerMetValPheAlaGluArgMetAlaGlu
Val Leu Ala Glu Gin Leu Ala Gly Val Ser Phe Pro Asp Ala Ser Thr Ser Phe Ala Cys1896]1835184018451897]AlaAlaAlaLeuSerGluPheValAspTrpAspLeuPheAla1898]1850185518601899]LeuAspAspProAlaValValAlaArgValAspValValGin1900]1865187018751901]AlaSerTrpAlaValMetValSerLeuAlaAlaValTrpGin1902]1880188518901903]AlaGlyValArgProAspAlaValValGlyHisSerGinGly1904]1895190019051905]lieAlaAlaAlaCysValAlaGlyAlaValSerLeuArgAsp1906]1910191519201907]AlaArgValValThrLeuArgSerGinVallieAlaArgGly1908]1925193019351909]AlaGlyArgGlyAlaMetAlaSerValAlaLeuProAlaGin1910]1940194519501911]ValGluLeuValAspGlyAlaTrpValAlaAlaArgAsnGly1912]1955196019651913]AlaSerThrValValAlaGlyAlaProGluAlaValAspArg1914]1970197519801915]LeuAlaValHisGluAlaArgGlyValArgValArgArglie1916]1985199019951917]ValAspTyrAlaSerHisThrProHisValGluLeulieArg1918]2000200520101919]GluLeuLeuGlyVallieAlaGlyValAspSerArgAlaPro1920]2015202020251921]ValProTrpLeuSerThrValAspGlyThrTrpValGluGly1922]2030203520401923]LeuAspAlaGluTyrTrpTyrArgAsnLeuArgGluProVal1924]2045205020551925]PheGluProAlaAlaGlyGinLeuGinAlaGinGlyAspThr1926]2060206520701927]PheValGluValSerAlaSerProValLeuLeuGinAlaMet1928]2075208020851929]AspAspValValThrValAlaThrLeuArgArgAspAspGly1930]2090209521001931]AlaThrArgMetLeuThrAlaLeuAlaGinAlaTyrValGlu1932]2105211021151933]ValThrValAspTrpProAlaValLeuGlyThrThrAlaAla1934]212021252130
Val Pro Ala Glu Ala Leu Asp Pro Val Ala Asp Val Pro Gly Val Asp Asp Gly Arg1935]ValLeuAspLeuProThrTyrAlaPheGinHisGinArgTyrTrp1936]2135214021451937]LeuLysGlyValAspArgAlaAlaAlaAspGlyHisProLeuLeu1938]2150215521601939]GlyThrValValAlaLeuProGlySerAspGlyValValLeuThr1940]2165217021751941]GlyArgValSerLeuAlaThrHisAlaTrpLeuAlaAspHisAla1942]2180218521901943]ValArgGlySerValLeuLeuProGlyThrAlaPheValGluLeu1944]2195220022051945]ValValArgAlaAlaGlyGluValGlyCysAspValValAspGlu1946]2210221522201947]LeuVallieGluThrProLeuLeuLeuProGinThrGlyGlyVal1948]2225223022351949]GinMetSerValSerValAlaGluAlaAspGluSerGlyHisArg1950]2240224522501951]AlaValMetValPheSerGinAlaAspAsnThrAspThrTrpThr1952]2255226022651953]ArgHisValThrAlaThrValSerThrSerAspSerThrValSer1954]2270227522801955]GinProGluPheAlaAlaTrpProProProAlaGlyAlaGluPro1956]2285229022951957]LeuAspLeuSerAspPheTyrAspGinLeuThrGlyAlaGlyTyr1958]2300230523101959]GluTyrGlyProAlaPheGinGlyLeuArgThrAlaTrpArgAsp1960]2315232023251961]GlyAsnThrValPheAlaGluValAlaLeuAlaGluGluGinAla1962]2330233523401963]GinGluAlaAlaArgPheAlaValHisProAlaLeuLeuAspAla1964]2345235023551965]AlaLeuHisAlaSerAsnLeuSerThrLeuAspThrAlaGluGin1966]2360236523701967]GlyValArgLeuProPheSerTrpAsnGinValTrpValHisAla1968]2375238023851969]ThrGlyProValMetLeuArgValAlalieThrArgThrAlaAsp1970]2390239524001971]GlyTrpSerValLeuValAlaAspAspSerGlyArgProValAla1972]2405241024151973]SerValGlySerLeuValThrArgValValThrAlaAspAlaLeu1974]2420242524301975]GlySerAlaAlaAspGluLeuLeuAlaLeuThrTrpMetGlu1976]2435244024451977]ProAlaProGinGlyThrGlyLeuThrValGlyArgPheGlu1978]2450245524601979]LeuValSerGlyGlyAspValProValProGluValValVal1980]2465247024751981]ThrAlaLeuProGlySerSerGluThrProLeuAspProLeu1982]2480248524901983]ProLeuAlaGinThrArgThrLeuThrAlaGinValLeuGin1984]2495250025051985]ValGinAlaTrpLeuAlaGlyGluGlyPheThrAsnSerThr1986]2510251525201987]ValValArgThrGlyThrGlyLeuAlaAlaAlaGlyValSer1988]2525253025351989]LeuMetArgSerValGinSerGluHisProGlyArgPheVal1990]2540254525501991]ValGluCysAspAspAspThrLeuThrProAspGinLeuAla1992]2555256025651993]ThrValGlyLeuAspGluProArgLeuArgValCysAspGly1994]2570257525801995]PheGluValProArgLeuAlaArgAlaAsnThrProGluSer1996]2585259025951997]ProLeuThrlieProAspSerArgAlaTrpLeuLeuGluGin1998]2600260526101999]ArgSerGlyThrLeuArgAspLeuAlaLeuValProThrAsp2000]2615262026252001]AlaGluArgProLeuGinSerGlyGluValArgValAspVal2002]2630263526402003]AlaAlaGlyLeuAsnPheArgAspValValValAlaLeuGly2004]2645265026552005]ValAspAspLysArgLeuAlaGlyGlyGluAlaAlaGlyVal2006]2660266526702007]LeuGluValGlyProGluValGinAspLeuAlaProGlyAsp2008]2675268026852009]ValPheGlyLeuValGlyGlyGlyPheGlyArgSerAlalie2010]2690269527002011]AspArgArgMetLeuGlyVallieProAspGlyTrpSerPhe2012]270527102715
lie Asp Phe Asp Ala Leu Gly Leu Ala Arg Ser Pro Thr Arg Met Val Arg Ala Thr
57[2013]ThrAlaAlaSerValProValValPheAlaThrAlaTyrTyr[2014]272027252730[2015]LeuValAspLeuAlaGlyLeuSerAlaGlyGluSerValLeu[2016]273527402745[2017]HisAlaAlaAlaGlyGlyValGlyMetAlaAlaThrGinlie[2018]275027552760[2019]ArgHisLeuGlyAlaArglieTyrAlaThrAlaSerThrGly[2020]276527702775[2021]GinHislieLeuArgGluAlaGlyLeuGluAspThrHislie[2022]278027852790[2023]AspSerArgThrLeuSerPheGinGluThrPheLeuAsnAsn[2024]279528002805[2025]HisGlyGinGlyValAspValValLeuAsnSerLeuSerGly[2026]281028152820[2027]PheValAspAlaSerLeuAspLeuLeuProArgGlyGlyArg[2028]282528302835[2029]lieGluMetGlyLysThrAsplieArgAspProHisGinVal[2030]284028452850[2031]AlaAspArgProGlyThrThrTyrGinAlaPheAspLeuMet[2032]285528602865[2033]AlaGlyProAspArgLeuArgGlulielieThrGluLeuLeu[2034]287028752880[2035]LeuPheThrGinGlyValLeuLeuProLeuProValGinAla[2036]288528902895[2037]AsplieArgGinAlaArgAspAlaPheSerTrpMetSerArg[2038]290029052910[2039]ArgHislieGlyLyslieValLeuThrlieProArgArgPro[2040]291529202925[2041]ProAspGlyThrlieLeulieThrGlyGlySerGlyValLeu[2042]293029352940[2043]GlylieLeuAlaArgHisLeuAlaAlaGluHisGlyAlaArg[2044]294529502955[2045]LeuLeuLeuLeuSerArgThrThrProAspGinAlaLeulie[2046]296029652970[2047]GluLeuAlaGluLeuGlyAlaHisValAspThrAlaThrCys[2048]297529802985[2049]ValSerAspArgAlaGlyLeuAlaArgValLeuAlaGlyVal[2050]299029953000[2051]ProGluHisProLeuThrAlaVallieHisThrAlaGlyAla
Gly lie Ala Lys Ala Thr Asp Phe Thr Asp Thr Trp Ala Asp Ala His Lys Asp Ser Leu[2052]300530103015[2053]AspAspGlyValValGluSerLeuThrThrGinGinLeuAsp[2054]302030253030[2055]ValLeuArgProLysAlaAspGlyAlaTrpHisLeuHisGlu[2056]303530403045[2057]ThrGinAsnThrAspLeuAlaAlaPheValMetTyrSerSer[2058]305030553060[2059]AlaGlyValLeuGlySerAlaGlyGinGlyAsnTyrAlaAla[2060]306530703075[2061]AsnAlaPheValAspAlaLeuAlaGluGinArgArgGlyGlu[2062]308030853090[2063]LeuProAlaLeuAlaValAlaTrpGlyLeuTrpGluAspThr[2064]309531003105[2065]GlyLeuThrAlaLysMetThrAspThrAspArgAspArglie[2066]311031153120[2067]ArgGlyGlyLeuArgAlalieSerAlaGlyArgGlyMetGly[2068]312531303135[2069]LeuAspAlaAlaSerArgHisGlyGluProValLeuLeuAla[2070]314031453150[2071]SerMetGluProValArgAspValGluValProAlaLeuLeu[2072]315531603165[2073]LeuLeuHisArgProValAlaArgArgAlaAlaSerThrGly[2074]317031753180[2075]SerSerValGinTrpLeuAlaArgLeuAlaProValGluArg[2076]318531903195[2077]LysAlaLeuLeuLysLeuValCysAspGlyAlaAlaThrVal[2078]320032053210[2079]GlyHisAlaAspAlaSerThrlieProAlaThrGlyAlaPhe[2080]321532203225[2081]AspLeuGlyValAspSerLeuThrAlaValGluLeuArgAsn[2082]323032353240[2083]LeuAlaLysAlaThrGlyLeuArgLeuProAlaThrLeuVal[2084]324532503255[2085]AspTyrProThrProAlaAlaLeuAlaAlaArgLeuGluGlu[2086]326032653270[2087]PheThrGlyGluAsnProAlaProValArgThrSerValSer[2088]327532803285[2089]ValAlaGinAspGluProLeuAlalieValGlyMetAlaCys[2090]329032953300
Thr Leu Ala Ala Gly Ser Arg Leu Ala Arg Asp Glu Leu Arg Gly Phe Leu Val Arg2091]LeuProGlyGlyValSerSerProGluAspLeuTrpArgLeuLeu2092]3305331033152093]GluSerGlyThrAspAlaValSerGlyPheProThrAspArgGly2094]3320332533302095]TrpAspValGluAsnLeuPheGlyProAlaValGlyAsnSerTyr2096]3335334033452097]ArgLeuGinGlyGlyPheLeuAspAlaAlaAlaGlyPheAspAla2098]3350335533602099]SerPhePheGlylieSerProArgGluAlaLeuAlaMetAspPro2100]3365337033752101]GinGinArgLeuValLeuGluValSerTrpGluAlaPheGluArg2102]3380338533902103]AlaGlylieLysProGlySerValArgGlyThrAspThrGlyVal2104]3395340034052105]PheMetGlyAlaTyrProGlyGlyTyrGlylieGlyAlaAspLeu2106]3410341534202107]GlyGlyPheGlyThrThrAlaGlyAlaValSerValLeuSerGly2108]3425343034352109]ArgValSerTyrPhePheGlyPheGluGlyProAlaPheThrVal2110]3440344534502111]AspThrAlaCysSerSerSerLeuValAlaLeuHisGinAlaGly2112]3455346034652113]TyrAlaLeuArgGinGlyGluCysSerLeuAlaLeuValGlyGly2114]3470347534802115]ValThrValMetAlaThrProGinThrPheValGluPheAlaArg2116]3485349034952117]GinGlyGlyLeuAlaGlyAspGlyArgSerLysAlaPheAlaAsp2118]3500350535102119]SerAlaAspGlyAlaGlyPheSerGluGlyValGlyValLeuLeu2120]3515352035252121]ValGluArgLeuSerAspAlaArgArgAsnGlyHisGinValLeu2122]3530353535402123]AlaValValArgGlySerAlaValAsnGinAspGlyAlaSerAsn2124]3545355035552125]GlyLeuThrAlaProAsnGlyProSerGinGinArgVallieArg2126]3560356535702127]AlaAlaLeuSerAsnAlaGlyLeuSerThrAlaGluValAspVal2128]3575358035852129]ValGluAlaHisGlyThrGlyThrThrLeuGlyAspProlieGlu2130]3590359536002131]AlaGinAlaLeuMetAlaThrTyrGlyGinAspArgGluGin2132]3605361036152133]LeuLeuLeuGlySerValLysSerAsnLeuGlyHisThrGin2134]3620362536302135]AlaAlaGlyValSerGlyVallieLysMetValMetAlaLeu2136]3635364036452137]ArgGlyPheValProArgThrLeuHisValAspGluProSer2138]3650365536602139]HisValAspTrpSerAlaGlyAlaValGinLeuValThrGlu2140]3665367036752141]GinProTrpProGlyThrAspArgProArgArgAlaGlyVal2142]3680368536902143]SerPheGlylieSerGlyThrAsnAlaHisVallieLeuGlu2144]3695370037052145]AlaLeuProThrGinProAlaGlyAsnThrValValGluSer2146]3710371537202147]ProGluTrpValProLeuVallieSerAlaArgThrGinSer2148]3725373037352149]LeuAlaGluTyrGluGlyArgLeuArgAlaTyrLeuAlaAla2150]3740374537502151]ProGlyAlaAspThrArgAlaValAlaSerThrLeuAlaMet2152]3755376037652153]ArgSerValPheGluTyrArgAlaValLeulieGlyAspAsp2154]3770377537802155]ValThrGlyThrAlaAlaThrAspProArgValValPheVal2156]3785379037952157]ProGlyGinGlySerGinArgAlaGlyMetGlyGluGluLeu2158]3800380538102159]AlaAlaPheProValPheAlaArglieHisGinGinValTrp2160]3815382038252161]LeuLeuAspValProAspLeuAspValAsnGluThrGlyTyr2162]3830383538402163]GinProAlaLeuPheAlaLeuGinValAlaLeuPheGlyLeu2164]3845385038552165]GluSerTrpGlyValArgProAspAlaValValGlyHisSer2166]3860386538702167]GlyGluLeuAlaAlaGlyTyrValSerGlyLeuTrpSerLeu2168]387538803885
612169]AspAlaCysThrLeuValSerAlaArgAlaArgLeuMetGinAla2170]3890389539002171]LeuProAlaGlyGlyValMetAlaAlaValProValSerGluAsp2172]3905391039152173]GluAlaArgAlaValLeuGlyGluGlyValGlulieAlaAlaVal2174]3920392539302175]AsnGlyProSerSerValValLeuSerGlyAspGluAlaAlaVal2176]3935394039452177]LeuGinAlaAlaGluGlyLeuGlyLysTrpThrArgLeuProThr2178]3950395539602179]SerHisAlaPheHisSerAlaArgMetGluProMetLeuGluGlu2180]3965397039752181]PheArgAlaValAlaGluGlyLeuThrTyrArgThrProGinVal2182]3980398539902183]AlaMetAlaAlaGlyAspGinValMetThrAlaGluTyrTrpVal2184]3995400040052185]ArgGinValArgAspThrValArgPheGlyGluGinValAlaSer2186]4010401540202187]PheGluAspAlaValPheValGluLeuGlyAlaAspArgSerLeu2188]4025403040352189]AlaArgLeuValAspGlylieAlaMetLeuHisGlyAspHisGlu2190]4040404540502191]AlaGinAlaAlaValGlyAlaLeuAlaHisLeuTyrValAsnGly2192]4055406040652193]ValSerValGluTrpSerAlaValLeuGlyAspValProValThr2194]4070407540802195]ArgValLeuAspLeuProThrTyrAlaPheGinHisGinArgTyr2196]4085409040952197]TrpLeuGluGlyThrAspArgAlaThrAlaGlyGlyHisProLeu2198]4100410541102199]LeuGlySerValValArgLeuAlaGluAlaSerGlyValLeuPhe2200]4115412041252201]ThrAlaArgValSerArgSerGlyAspLeuTrpLeuArgAspGin2202]4130413541402203]ThrValLeuProAlaThrValPheValGluMetAlaLeuAlaAla2204]4145415041552205]AlaAspGluValGlyCysGlyLeuValGluAspLeuSerValGlu2206]4160416541702207]AlaLeuLeuLeuLeuProAspAspGlyAlaValGluValGinThr[2208]417541804185[2209]TrpValGlyGluProAspGluGlyGlyArgArgArgLeuSer[2210]419041954200[2211]HisAlaArgTyrGlyAspGlyGluProTrpThrCysLeuAla[2212]420542104215[2213]AlaThrLeuAlaThrThrThrGlyValAlaAlaAlaAlaVal[2214]422042254230[2215]TrpGlnAlaGlyGlyValTrpProProAlaGlyAlaValPro[2216]423542404245[2217]GlyThrSerAlaProSerLeuArgAlaValTrpArgLeuGly[2218]425042554260[2219]AspliePheAlaGluValAlaLeuAspAspAlaHisAspAla[2220]426542704275[2221]ArgPheValLeuHisProAlaLeuMetAlaAlaAlaLeuThr[2222]428042854290[2223]ValGlyGluGluThrProAlaValTrpGlnGlyLeuThrLeu[2224]429543004305[2225]AlaGlyAsnProGlyGluLeuArgValArgLeuThrSerHis[2226]431043154320[2227]AspGlyThrLeuSerAlaGluAlaThrAspSerThrGlyLeu[2228]432543304335[2229]ValLeuThrAlaArgSerLeuThrLeuArgThrValProVal[2230]434043454350[2231]GluProAlaThrSerThrAspAspLeuLeuThrLeuThrTrp[2232]435543604365[2233]GlylieProThrProGlnGlnThrGlyLeuThrValGlyAla[2234]437043754380[2235]GluAspLeuAlaAlaAspGlyAspValProValProGluVal[2236]438543904395[2237]ValPheThrAlaLeuProAspSerAspAspProLeuGluGln[2238]440044054410[2239]ArgLysLeuThrAlaGlnValLeuHisThrLeuGlnGluTrp[2240]441544204425[2241]GlyGlyGluArgPheSerAspSerThrLeuValValArgThr[2242]443044354440[2243]ThrGlyLeuAlaAlaAlaGlyValSerGlyLeuMetArgSer[2244]444544504455[2245]GlnSerGluHisProGlyArgPheValLeuValGluSerAsp[2246]446044654470
Val Thr Gly Val Ser Thr Thr His Asp Pro Tyr Ala Phe Ala Thr Leu Gly Ala Asp[2247]AlaLeuThrGlnAspGlnLeuAlaAlaAlaValGlyLeuAsp[2248]447544804485[2249]ProArgLeuArgValSerAspGlyArgTyrGluValProArg[2250]449044954500[2251]ThrArgThrHisAlaGluGluProGluProGluArgThrTrp[2252]450545104515[2253]ProAspGlyThrValLeulieThrGlyGlySerGlyValLeu[2254]452045254530[2255]GlylieAlaAlaArgHisLeuValThrGluArgGlyValArg[2256]453545404545[2257]LeuLeuLeuLeuSerArgSerAlaProAspGluAlaLeulie[2258]455045554560[2259]GluLeuGlyGluLeuGlyAlaArgValGluThrAlaAlaCys[2260]456545704575[2261]ValSerAspProAlaAlaLeuThrGlnValLeuAlaGlyVal[2262]458045854590[2263]ProGluHisProLeuThrAlaVallieHisThrAlaGlyVal[2264]459546004605[2265]AspAspGlyValValGluSerLeuThrValGlnArgLeuGlu[2266]461046154620[2267]ValLeuArgProLysAlaAspGlyAlaTrpAsnLeuHisGlu[2268]462546304635[2269]ThrArgAspAlaAspLeuAlaAlaPheValMetTyrSerSer[2270]464046454650[2271]AlaGlyValLeuGlySerAlaGlyGlnAlaAsnTyrAlaAla[2272]465546604665[2273]AsnAlaPheLeuAspAlaLeuAlaGluGlnArgHisAlaGlu[2274]467046754680[2275]LeuProAlaLeuAlaValAlaTrpGlyLeuTrpGluAspAla[2276]468546904695[2277]GlyLeuThrAlaGlnLeuThrAspThrAspArgAspArglie[2278]470047054710[2279]ArgGlyGlyLeuArgAlalieSerAlaGluHisGlyMetGly[2280]471547204725[2281]PheAspSerAlaSerArgHisSerGluProValLeuValAla[2282]473047354740[2283]ProMetGluProValArgAspAlaGluValProAlaLeuLeu[2284]474547504755[2285]SerLeuHisArgProlieAlaArgArgAlaAlaAlaAlaGly
Glu Leu Asp Ala His Gly Asp Ser Val Thr Leu Ala Ala Gly Ser Arg Leu Ala Arg Gly[2286]476047654770[2287]AlaArgTrpLeuAlaAlaLeuAlaProAlaGluArgGluLys[2288]477547804785[2289]LeuLeuLysLeuValCysAspSerAlaAlaThrValLeuGly[2290]479047954800[2291]AlaAspThrSerThrValSerValAlaAlaValPheArgAsp[2292]480548104815[2293]GlyValAspSerLeuThrAlaValGluLeuArgAsnSerLeu[2294]482048254830[2295]LysAlaThrGlyLeuArgLeuProAlaThrLeuValPheAsp[2296]483548404845[2297]ProThrProThrAlaLeuAlaValArgLeuGlyGluLeuPhe[2298]485048554860[2299]GlyGluAsnProValProValArgGlyProValSerAlaVal[2300]486548704875[2301]GinAspGluProLeuAlalieValGlyMetAlaCysArgLeu[2302]488048854890[2303]GlyGlyValSerSerProGluAspLeuTrpArgLeuLeuGlu[2304]489549004905[2305]GlyThrAspAlaValSerGlyPheProThrAspArgGlyTrp[2306]491049154920[2307]ValGluAsnLeuTyrAspMetAlaGlyLysSerHisArgAla[2308]492549304935[2309]GlyGlyPheLeuAspAlaAlaAlaGlyPheAspAlaGlyPhe[2310]494049454950[2311]GlylieSerProArgGluAlaLeuAlaMetAspProGinGin[2312]495549604965[2313]LeuValLeuGluValSerTrpGluAlaPheGluArgAlaGly[2314]497049754980[2315]GluProGlySerValArgGlySerAspThrGlyValPheMet[2316]498549904995[2317]AlaTyrProGlyGlyTyrGlyAlaGlyAlaAspLeuGlyGly[2318]500050055010[2319]AlaAlaThrAlaSerAlaThrSerValLeuSerGlyArgVal[2320]501550205025[2321]TyrPhePheGlyLeuGluGlyProAlaPheThrValAspThr[2322]503050355040[2323]CysSerSerSerLeuValAlaLeuHisGinAlaGlyTyrAla[2324]504550505055
Ala His Leu Ala Tyr Thr Ala Pro Ser Asp Glu Phe Arg lie Gly Phe Ser Ala Leu[2325]ArgGlnGlyGluCysSerLeuAlaLeuValGlyGlyValThr[2326]506050655070[2327]MetAlaThrProGluLeuPheThrGluPheSerArgGlnArg[2328]507550805085[2329]LeuAlaSerAspGlyArgCysLysAlaPheAlaAspSerAla[2330]509050955100[2331]GlyThrGlyTrpAlaGluGlyValGlyValLeuLeuValGlu[2332]510551105515[2333]LeuSerAspAlaGlnAlaLysGlyHisGlnValLeuAlaVal[2334]512051255130[2335]ArgSerSerAlaValAsnGlnAspGlyAlaSerAsnGlyLeu[2336]513551405145[2337]AlaProAsnGlyProSerGlnGlnArgVallieGlnAlaAla[2338]515051555160[2339]SerAsnAlaGlyLeuAlaAlaHisGluValAspValValGlu[2340]516551705175[2341]HisGlyThrGlyThrThrLeuGlyAspProlieGluAlaGln[2342]518051855190[2343]VallieAlaThrTyrGlyGlnAspArgGluArgProLeuLeu[2344]519552005205[2345]GlySerLeuLysSerAsnlieGlyHisAlaGlnAlaAlaSer[2346]521052155220[2347]ValSerValVallieLysMetValMetAlaLeuGlnHisAsn[2348]522552305235[2349]ValProArgThrLeuHisValAspGluProSerArgHisVal[2350]524052455250[2351]TrpAlaAlaGlyAlaValGluLeuValArgGluAsnGlnPro[2352]525552605265[2353]ProGlyThrAspArgProArgArgAlaGlyValSerSerPhe[2354]527052755280[2355]ValSerGlyThrAsnAlaHisVallieLeuGluSerAlaPro[2356]528552905295[2357]AlaGlnProAlaGluGluAlaGlnProValGluThrProVal[2358]530053055310[2359]AlaSerAspValLeuProLeuVallieSerAlaLysThrGln[2360]531553205325[2361]AlaLeuThrGluHisGluAspArgLeuArgAlaTyrLeuAla[2362]533053355340[2363]SerProGlyAlaAspThrArgAlaValAlaSerThrLeuAla[2364]534553505355[2365]ThrArgSerValPheGluHisArgAlaValLeuLeuGlyAsp[2366]536053655370[2367]ThrValThrGlyThrAlaValSerAspProArgValValPhe[2368]537553805385[2369]PheProGlyGlnGlyTrpGlnTrpLeuGlyMetGlySerAla[2370]539053955400[2371]ArgAspSerSerValValPheAlaGluArgMetAlaGluCys[2372]540554105415[2373]AlaAlaLeuSerGluPheValAspTrpAspLeuThrValLeu[2374]542054255430[2375]AspProAlaValValAspArgValAspValValGlnProAla[2376]543554405445[2377]TrpAlaValMetValSerLeuAlaAlaValTrpGlnAlaAla[2378]545054555460[2379]ValArgProAspAlaVallieGlyHisSerGlnGlyGlulie[2380]546554705475[2381]AlaAlaCysValAlaGlyAlaValSerLeuArgAspAlaAla[2382]548054855490[2383]lieValThrLeuArgSerGlnAlalieAlaArgGlyLeuAla[2384]549555005505[2385]ArgGlyAlaMetAlaSerValAlaLeuProAlaGlnAspVal[2386]551055155520[2387]LeuValAspGlyAlaTrplieAlaAlaHisAsnGlyProAla[2388]552555305535[2389]ThrVallieAlaGlyThrProGluAlaValAspHisValLeu[2390]554055455550[2391]AlaHisGluAlaArgGlyValArgValArgArglieThrVal[2392]555555605565[2393]TyrAlaSerHisThrProHisValGluLeulieArgAspGlu[2394]557055755580[2395]LeuAsplieThrSerAspSerSerSerGlnAlaProLeuVal[2396]558555905595[2397]TrpLeuSerThrValAspGlySerTrpValAspSerProLeu[2398]560056055610[2399]GlyGluTyrTrpTyrArgAsnLeuArgGluProValGlyPhe[2400]561556205625[2401]ProAlaValGlyGlnLeuGlnAlaGlnGlyAspThrValPhe[2402]563056355640
Asp Val Leu Ala Asp Ser Gly Ala Arg Gly Glu Ser Thr Asp Leu Pro Asp His Val[2403]GluValSerAlaSerProValLeuLeuGinAlaMetAspAsp[2404]564556505655[2405]ValValThrValAlaThrLeuArgArgAspAspGlyAspAla[2406]566056655670[2407]ArgMetLeuThrAlaLeuAlaGinAlaTyrValHisGlyVal[2408]567556805685[2409]ValAspTrpProAlalieLeuGlyThrThrThrThrArgVal[2410]569056955700[2411]AspLeuProThrTyrAlaPheGinHisGinArgTyrTrpVal[2412]570557105715[2413]GlyValAspArgSerAlaAlaGlyGlyHisProLeuLeuGly[2414]572057255730[2415]AlaValGluLeuProAspSerAsnGlyValValLeuThrGly[2416]573557405745[2417]ValSerLeuAlaThrHisThrTrpLeuAlaAspHisAlaVal[2418]575057555760[2419]GlySerValLeuLeuProGlyThrAlaPheValGluLeuVal[2420]576557705775[2421]ArgAlaAlaAspGluValGluCysAspVallieAspGluLeu[2422]578057855790[2423]lieGluThrProLeuLeuLeuProGinThrGlyGlyValGin[2424]579558005805[2425]SerValSerValAlaGluAlaAspGluSerGlyHisArgAla[2426]581058155820[2427]ThrValPheSerArgAlaAspAsnAlaAspThrTrpThrArg[2428]582558305835[2429]ValSerAlaThrlieSerAlaSerAspAlaProLeuSerLeu[2430]584058455850[2431]GluPheAlaSerTrpProProAlaGinAlaGinProThrAsn[2432]585558605865[2433]GlyAspLeuTyrAspArgLeuAlaAlaAlaGlyThrGluTyr[2434]587058755880[2435]ProAlaPheGinGlyLeuGinAlaAlaTrpArgAspGlyAsp[2436]588558905895[2437]AlaTyrAlaGluValAlaLeuAlaGluGluGinAlaGinGlu[2438]590059055910[2439]AlaArgPheAlaValHisProAlaLeuLeuAspAlaAlaLeu[2440]591559205925[2441]AlaSerValLeuHisThrProAspAlaGluGinGinSerLeu
Asp Thr Thr Leu Glu Val Arg Arg Val Val Leu Val His Pro Val Gly Thr Ala His Arg
68[2442]593059355940[2443]MetProPheSerTrpSerHisValGlnValHisAlaThrGly[2444]594559505955[2445]AlaThrLeuArgValAlaMetThrProThrThrAspGlyTrp[2446]596059655970[2447]ValHisValAlaAspAspAspGlyArgProValAlaThrlie[2448]597559805985[2449]SerPheValThrArgProValThrAlaAspAlaLeuGlySer[2450]599059956000[2451]AlaAspAspLeuLeuArgValValTrpThrGlulieProlie[2452]600560106015[2453]GlnGlnThrGlyLeuThrThrGlyArgPheGluAspLeuVal[2454]602060256030[2455]AlaAspValProValProGluValValValTyrThrAlaArg[2456]603560406045[2457]AspThrAspGlySerProAspProLeuAlaGlnThrArgThr[2458]605060556060[2459]ThrAlaGlnValLeuGlnAlaValGlnAlaTrpLeuAlaGly[2460]606560706075[2461]ArgPheThrAspSerThrLeuValValArgThrGlyThrGly[2462]608060856090[2463]AlaAlaAlaAlaValSerGlyLeuMetArgSerValGlnSer[2464]609561006105[2465]HisProGlyArgPheValLeuValGluGlyAspAspAspThr[2466]611061156120[2467]ThrProAspGlnLeuAlaAlaThrAlaGlyLeuAspGluPro[2468]612561306135[2469]LeuArgValCysAspGlyArgPheGluValProArgLeuAla[2470]614061456150[2471]AlaAsnThrProGluSerSerProLeuThrlieProAspAsp[2472]615561606165[2473]AlaTrpLeuLeuGluGlnProArgSerGlyThrLeuGlnAsp[2474]617061756180[2475]AlaLeuValProThrAspThrAlaGluArgProLeuArgPro[2476]618561906195[2477]GluValArglieAspValArgAlaAlaGlyLeuAsnPheArg[2478]620062056210[2479]ValLeulieAlaLeuGlyThrTyrProGlyGluAlaVallie[2480]621562206225[2481]AlaGluAlaAlaGlyValValLeuGluValGlyProGluAla[2482]623062356240[2483]AspLeuAlaProGlyAspArgValPheGlyLeuValGlyGly[2484]624562506255[2485]PheGlyAlaValAlalieAlaAspArgArgMetLeuAlaVal[2486]626062656270[2487]ProAspGlyTrpSerPheThrThrAlaAlaSerValProVal[2488]627562806285[2489]PheAlaThrAlaTyrTyrGlyLeuValAspLeuGlyGlyLeu[2490]629062956300[2491]AlaGlyGluSerValLeulieHisAlaAlaAlaGlyGlyVal[2492]630563106315[2493]MetAlaAlaThrGlnlieAlaArgHisLeuGlyAlaGlnlie[2494]632063256330[2495]AlaThrAlaSerAlaGlyLysGlnHislieLeuTyrGluAla[2496]633563406345[2497]LeuAspGlyThrArglieAlaAspSerArgThrThrGlyPhe[2498]635063556360[2499]GluAlaPheLeuAsnThrThrAspGlyArgGlyValAspVal[2500]636563706375[2501]LeuAsnSerLeuSerGlyAspPheValAspAlaSerLeuAsp[2502]638063856390[2503]LeuProArgGlyGlyArgPheValGlulieGlyLysThrAsp[2504]639564006405[2505]ArgAspProHisArglieThrAlaAspArgProGlyThrThr[2506]641064156420[2507]GlnAlaCysAspLeuMetAspValGlyProAspArgLeuArg[2508]642564306435[2509]lielieThrGlulieLeuSerLeuPheGlyGlnGlyValLeu[2510]644064456450[2511]ProLeuProValGlnThrTrpAsplieArgGlnAlaArgAsp[2512]645564606465[2513]PheSerTrpMetSerArgAlaArgHislieGlyLyslieVal[2514]647064756480[2515]ThrlieProArgArgProAspProAspGlyThrlieLeulie[2516]648564906495[2517]GlyGlySerGlyValLeuAlaGlylieLeuAlaArgHisLeu[2518]650065056510[2519]AlaGluHisGlyAlaArgHisLeuLeuLeuLeuSerArgThr
His Gly Ile Val Ser Gly Tyr Gly Arg Val Leu Ile Tyr Glu Gln Ala Leu Thr Ala Ala[2520]651565206525[2521]ProAspGluAlaLeulieLysGluLeuAlaGluLeuGlyAla[2522]653065356540[2523]ValGluThrAlaAlaCysAspValSerAspArgAlaGlyLeu[2524]654565506555[2525]ArgValLeuAlaGlyValSerProGluHisProLeuThrAla[2526]656065656570[2527]lieHisThrAlaGlyAlaLeuAspAspGlyValValGluSer[2528]657565806585[2529]ThrThrGinGinLeuAspThrValLeuArgProLysAlaAsp[2530]659065956600[2531]AlaTrpHisLeuHisGluLeuThrArgAspAlaAspLeuAla[2532]660566106615[2533]PheValValTyrSerSerAlaAlaAlaValLeuGlyAsnGlu[2534]662066256630[2535]GinGlyAsnTyrAlaAlaAlaAsnAlaPheLeuAspAlaLeu[2536]663566406645[2537]GluGinArgArgThrGinGlyLeuProAlaLeuAlaLeuAla[2538]665066556660[2539]GlyProTrpGluTyrThrGlyAspLeuThrAlaGinLeuThr[2540]666566706675[2541]ThrAspGinAspArglieArgCysSerGlyMetArgThrlie[2542]668066856690[2543]AlaGluAspGlyMetArgLeuPheAspThrAlaSerHisHis[2544]669567006705[2545]GluProLeuLeuValProAlaValLeuAspProThrArgAsp[2546]671067156720[2547]GluValProAlaLeuLeuArgSerLeuArgArgProlieAla[2548]672567306735[2549]ArgAlaAlaSerAlaAspGlyGlyValGinTrpLeuAlaAla[2550]674067456750[2551]AlaProAlaGluArgGluLysAlaLeuLeuLysLeuValCys[2552]675567606765[2553]SerAlaAlaMetValLeuGlyHisAlaAspAlaArgSerlie[2554]677067756780[2555]AlaAlaGlyAlaPheLysAspLeuGlyValAspSerLeuMet[2556]678567906795[2557]ValGluLeuArgAsnGlyLeuValLysAlaThrGlyLeuArg[2558]680068056810
Arg Ala Val Leu Gly Ala Gly Ala Trp Gly Thr Gly Gly Arg Leu Asp Pro Ala Leu[2559]ProAlaThrLeuValPheAspTyrProThrProThrValLeu[2560]681568206825[2561]AlaArgLeuAspGluLeuPheThrGlyGluAsnProAlaPro[2562]683068356840[2563]ArgGlyProValSerValValGlyGlnAspGluProLeuAla[2564]684568506855[2565]ValGlyMetAlaCysArgLeuProGlyGlyValSerSerPro[2566]686068656870[2567]AspLeuTrpArgLeuValGluSerGlyThrAspAlaValSer[2568]687568806885[2569]PheProThrAspArgGlyTrpAspValGluAsnLeuTyrAsp[2570]689068956900[2571]AspProGluAlaAlaGlyLysSerTyrCysValGlnGlyGly[2572]690569106915[2573]LeuAspThrAlaAlaGlyPheAspAlaGlyPhePheGlylie[2574]692069256930[2575]ProArgGluAlaLeuAlaMetAspProGlnGlnArgLeuLeu[2576]693569406945[2577]GluValSerTrpGluAlaPheGluArgAlaGlylieGluPro[2578]695069556960[2579]SerValArgGlySerAspThrGlyValPhelieGlyAlaPhe[2580]696569706975[2581]ValGlyTyrGlyAlaGlyPheAspArgGluGlyTyrGlyAla[2582]698069856990[2583]SerGlyProSerValLeuSerGlyArgValSerTyrValPhe[2584]699570007005[2585]LeuGluGlyProAlalieThrMetAspThrAlaCysSerSer[2586]701070157020[2587]LeuValAlaLeuHisLeuAlaAlaGlnAlaLeuArgAsnGly[2588]702570307035[2589]CysSerMetAlaLeuAlaGlyGlyValThrValMetAlaThr[2590]704070457050[2591]GluValPheThrGluPheAlaArgGlnArgGlyLeuAlaSer[2592]705570607065[2593]GlyArgCysLysAlaPheAlaAspSerAlaAspGlyAlaGly[2594]707070757080[2595]SerGluGlyAlaGlyLeuLeuLeuValGluArgLeuSerAsp[2596]708570907095[2597]ArgArgAsnGlyHisGlnValLeuAlaValValArgGlySer
Ala Val Ile Glu Gly Ser Phe Ser Leu Gly Pro Thr Gly Ser Glu Pro Asp Phe Ala Ala
72[2598]710071057110[2599]ValAsnGinAspGlyAlaSerAsnGlyLeuThrAlaProAsn[2600]711571207125[2601]ProSerGinGinArgVallieArgAlaAlaLeuSerAsnAla[2602]713071357140[2603]LeuSerThrAlaAspValAspValValGluAlaHisGlyThr[2604]714571507155[2605]ThrThrLeuGlyAspProlieGluAlaGinAlaLeuLeuAla[2606]716071657170[2607]TyrGlyGinAspArgGluGinProLeuLeuLeuGlySerLeu[2608]717571807185[2609]SerAsnlieGlyHisThrGinAlaAlaSerGlyValSerGly[2610]719071957200[2611]lieLysMetValMetAlaLeuArgHisGlyPheValProArg[2612]720572107215[2613]LeuHisValAspGluProSerArgHisValAspTrpAlaAla[2614]722072257230[2615]AlaValGluLeuValArgGluAsnGinProTrpProGlyThr[2616]723572407245[2617]ArgProArgArgAlaGlyValSerSerPheGlyValSerGly[2618]725072557260[2619]AsnAlaHisValValLeuGluSerAlaProProAlaGinPro[2620]726572707275[2621]GluGluGluGinProValGluThrProValValAlaSerAsp[2622]728072857290[2623]LeuProLeuVallieSerAlaLysThrGinProAlaLeuThr[2624]729573007305[2625]HisGluAspArgLeuArgAlaTyrLeuAlaAlaSerProGly[2626]731073157320[2627]AspThrArgAlaValAlaSerThrLeuAlaValThrArgSer[2628]732573307335[2629]PheGluHisArgAlaValLeuLeuGlyAspAspAlaValThr[2630]734073457350[2631]ThrAlaValThrAspProArgValValPheValPheProGly[2632]735573607365[2633]GlyTrpGinTrpLeuGlyMetGlySerAlaLeuArgAspSer[2634]737073757380[2635]ValValPheAlaGluArgMetAlaGluCysAlaAlaAlaLeu[2636]738573907395
Gly Gly Gly Thr Lys Val Thr Gly Asp Thr Ala Val Glu Ala Val Gly Gin Ser Ser[2637]GluPheValAspTrpAspLeuPheAlaValLeuAspAspPro[2638]740074057410[2639]ValValAspArgValAspValValGlnProAlaSerTrpAla[2640]741574207425[2641]MetValSerLeuAlaAlaValTrpGlnAlaAlaGlyValArg[2642]743074357440[2643]AspAlaVallieGlyHisSerGlnGlyGlulieAlaAlaAla[2644]744574507455[2645]ValAlaGlyAlaValSerLeuArgAspAlaAlaArglieVal[2646]746074657470[2647]LeuArgSerGlnAlalieAlaArgGlyLeuAlaGlyArgAla[2648]747574807485[2649]MetAlaSerValAlaLeuProAlaHisGlulieGluLeuVal[2650]749074957500[2651]GlyAlaTrplieAlaAlaHisAsnGlyProAlaSerThrVal[2652]750575107515[2653]AlaGlyThrProGluAlaValAspHisValLeuThrAlaHis[2654]752075257530[2655]AlaArgGlyValArgValArgArglieThrValAspTyrAla[2656]753575407545[2657]HisThrProHisValGluLeulieArgAspGluLeuLeuGly[2658]755075557560[2659]ThrAlaGlylieGlySerGlnProProValValProTrpLeu[2660]756575707575[2661]ThrValAspGlySerTrpValAspSerProLeuAspGlyGlu[2662]758075857590[2663]TrpTyrArgAsnLeuArgGluProValGlyPheHisProAla[2664]759576007605[2665]SerGlnLeuGlnAlaGlnGlyAspAlaValPheValGluVal[2666]761076157620[2667]AlaSerProValLeuLeuGlnAlaMetAspAspAspValVal[2668]762576307635[2669]ValAlaThrLeuArgArgAspAspGlyAspAlaThrArgMet[2670]764076457650[2671]ThrAlaLeuAlaGlnAlaTyrValHisGlyValThrValAsp[2672]765576607665[2673]ProAlalieLeuGlyThrThrThrAlaArgValLeuAspLeu[2674]767076757680[2675]ThrTyrAlaPheGlnHisGlnArgTyrTrpValLysSerVal
Ala Val Pro Cys Thr Ala Asp Ile Glu Ser Ile Ser Tyr Val Ser Thr Leu Trp Pro Asp2676]7685769076952677]ArgAlaAlaAlaAspGlyHisProLeuLeuGlyAlaValVal2678]7700770577102679]LeuProGluSerAspGlyValLeuLeuThrGlyArgValSer2680]7715772077252681]AlaThrHisAlaTrpLeuAlaAspHisAlaValTrpGlyArg2682]7730773577402683]LeuLeuProGlyThrAlaPheValGluLeuValValHisAla2684]7745775077552685]GlyGluValGlyCysAspValValAspGluLeuVallieGlu2686]7760776577702687]ProLeuLeuLeuProGinThrGlyGlyValGinLeuSerVal2688]7775778077852689]ValGlyGluAlaAspGluSerGlyHisArgValValThrVal2690]7790779578002691]SerArgAlaAspAsnAlaAspThrTrpThrArgHisValSer2692]7805781078152693]ThrValArgValSerAspThrThrValProProSerAspLeu2694]7820782578302695]AlaTrpProProAlaGinAlaLysProValAspValAlaGly2696]7835784078452697]TyrAspGinLeuThrGlyMetGlyTyrGluTyrGlyProAla2698]7850785578602699]GinGlyLeuGinAlaAlaTrpArgAspGlyAspThrValPhe2700]7865787078752701]GluValAlaLeuAlaGluGluGinValArgGluAlaAlaArg2702]7880788578902703]AlaValHisProAlaLeuLeuAspAlaAlaLeuHisAlaCys2704]7895790079052705]LeuAsnAlaSerAspAlaGluValGlyValGlyLeuProPhe2706]7910791579202707]TrpAsnGlyValArgValHisAlaGlyGlySerAlaMetLeu2708]7925793079352709]ValAlaValThrGinAlaAlaAspGlyTrpSerValArgVal2710]7940794579502711]AspAsplieGlyArgProValAlaSerValGlySerLeuVal2712]7955796079652713]ArgProValThrAlaAspAlaLeuGlySerAlaAlaAspAsp2714]7970797579802715]LeuAlaLeuThrTrpAlaGlylieProThrProGlnGlnThrGly2716]7985799079952717]LeuThrValGlyArgPheGluGluLeuValSerAspGlyAspVal2718]8000800580102719]ProValProGluValAlaValPheThrAlaLeuProAspAsnAsp2720]8015802080252721]AspAspProLeuGluGlnThrArgLysLeuThrGlyGlnValLeu2722]8030803580402723]GlnAlaValGlnGluTrpLeuGlyGlyGluArgPheSerAspSer2724]8045805080552725]ThrLeuValValArgThrGlyThrGlyLeuAlaAlaAlaAlaVal2726]8060806580702727]SerGlyTrpMetArgSerAlaGlnSerGluHisProGlyArgPhe2728]8075808080852729]ValLeuValGluSerAspAspAspAlaLeuAlaProAspGlnLeu2730]8090809581002731]AlaAlaAlaValGlyLeuAspGluProArgLeuArglieSerAsp2732]8105811081152733]GlyArgPheGluAlaProArgLeuThrArgThrHisAlaAlaGlu2734]8120812581302735]ProGluSerGluLysValTrpAspProAspGlyThrValLeulie2736]8135814081452737]ThrGlyGlySerGlyValLeuAlaGlylieAlaAlaArgHisLeu2738]8150815581602739]ValAlaGluArgGlyValArgHisLeuLeuLeuLeuSerArgSer2740]8165817081752741]AlaProAspGluAlaLeulieAsnGlnLeuGlyGluLeuGlyAla2742]8180818581902743]ArgValGluThrAlaAlaCysAspValSerAspArgAlaAlaLeu2744]8195820082052745]AlaGlnValLeuAlaGlyValSerProGluHisProLeuThrAla2746]8210821582202747]VallieHisThrAlaGlyAlaLeuAspAspGlyValValGluSer2748]8225823082352749]LeuThrAlaGlnArgLeuAspAlaValLeuArgProLysAlaAsp2750]8240824582502751]GlyAlaTrpAsnLeuHisGluLeuThrArgAspAlaAspLeuAla2752]8255826082652753]AlaPheValMetTyrSerSerAlaAlaGlyValLeuGlySerAla[2754]827082758280[2755]GlyGlnAlaAsnTyrAlaAlaAlaAsnAlaPheValAspAlaLeu[2756]828582908295[2757]AlaGluGlnArgArgAlaGluGlyLeuProAlaLeuAlaValAla[2758]830083058310[2759]TrpGlyLeuTrpGluAspAlaSerGlyLeuThrAlaAspLeuThr[2760]831583208325[2761]AspThrAspArgAspArglieArgArgGlyGlyLeuArgAlalie[2762]833083358340[2763]SerAlaGluTyrGlyMetGlyLeuPheAspSerAlaSerArgHis[2764]834583508355[2765]SerGluProValLeuValGlyAlaAlaMetGluProValArgAsp[2766]836083658370[2767]AlaGluValProAlaLeuLeuArgSerLeuHisArgProlieAla[2768]837583808385[2769]ArgArgAlaAlaSerThrGlyAspSerSerValGlnTrpLeuAla[2770]839083958400[2771]AlaLeuAlaProGluGluArgAlaLysAlaLeuLeuArgValVal[2772]840584108415[2773]CysAspSerAlaAlaThrValLeuGlyHisAlaAsplieAspSer[2774]842084258430[2775]lieProValThrAlaAlaPheLysAspLeuGlyValAspSerLeu[2776]843584408445[2777]ThrAlaValAspLeuArgAsnSerLeuAlaLysAlaThrGlyLeu[2778]845084558460[2779]ArgLeuProProThrLeuValPheAspTyrProThrProThrAla[2780]846584708475[2781]LeuAlaAlaArgLeuAspGluLeuPheAlaProAlaGluProGlu[2782]848084858490[2783]ProArgLeuHisGluGlnGluLeuArgArgAlaLeuAlaGlylie[2784]849585008505[2785]SerlieAspLysPheArgGluAlaGlyValLeuAspThrLeuLeu[2786]851085158520[2787]ArgLeuAlaAlaMetGluGlyLeuAlaValProLysProAspSer[2788]852585308535[2789]GluSerAspAspGluAlaPheValAspGluMetAspAlaAspAla[2790]854085458550[2791]LeulieLysHisValLeuGluGluGluArg
权利要求
一种如SEQ ID NO1的核苷酸序列。
2.—种如SEQ ID NO :1的核苷酸序列的功能变异体。
3.一种含有如权利要求1或2任一所述的核苷酸序列的载体。
4.一种用权利要求4所述的载体转化的微生物。
5.一种权利要求1所述的核苷酸序列编码的氨基酸序列。
6.一种如权利要求5所述的氨基酸序列的功能变异体或突变体。
7.一种含有权利要求5或6任一所述的氨基酸序列或其部分的蛋白质。
8.一种游动放线菌雷帕霉素生物合成聚酮合成酶的制备方法，其特征在于，所述的方 法包括步骤培养如权利要求4所述的微生物，从培养基中分离游动放线菌雷帕霉素生物 合成聚酮合成酶。
9.一种如权利要求1所述的核苷酸序列在鉴定游动放线菌雷帕霉素生物合成聚酮合 成酶结构基因和调节基因中的应用。
10.一种如权利要求1所述的核苷酸序列在通过增加基因剂量，或使用更有效的启动 子或通过基因操作(如对调节基因蛋白表达或调节基因识别位点的基因操作)改变调控作 用来提高游动放线菌雷帕霉素生物合成聚酮合成酶合成的产量上的应用。
11.一种如权利要求1所述的核苷酸序列在分离与游动放线菌雷帕霉素生物合成聚酮 合成酶相关的天然物质的生物合成基因中的应用。
12.—种如权利要求1所述的核苷酸序列在消除不需要的游动放线菌雷帕霉素生物合 成聚酮合成酶额外组分生物合成途径中的应用。
13.—种如权利要求1所述的核苷酸序列在获得游动放线菌雷帕霉素生物合成聚酮合 成酶中的应用。
14.一种如权利要求1所述的核苷酸序列在获得雷帕霉素中的应用。
15.一种如权利要求1所述的核苷酸序列在由合成的或由微生物制备的前体合成雷帕 霉素或类似化合物中的应用。
全文摘要
本发明公开了来自游动放线菌的雷帕霉素生物合成基因及其分离方法和应用。所述基因为如SEQ ID NO1的核苷酸序列。
文档编号C12N1/00GK101886085SQ20091005130
公开日2010年11月17日 申请日期2009年5月15日 优先权日2009年5月15日
发明者朱宝泉, 胡海峰, 郭铭 申请人:上海医药工业研究院