CN1617740A - 抗沙眼衣原体的免疫 - Google Patents
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Abstract
从已发表的沙眼衣原体基因组序列中可以推断出超过1000种其编码的蛋白质,但是单从其自身无法判断哪个可作为抗原用于免疫和疫苗,或者用于诊断。本发明解决了这一问题,本发明提供了许多适于制造和开发疫苗和/或适用于诊断的沙眼衣原体蛋白质序列。
Description
本文引用的所有文献都已完整纳入本文作为参考。
技术领域
本发明属于抗衣原体感染免疫领域,特别是抗沙眼衣原体感染。
背景领域
衣原体属于真核细胞内的寄生虫,能引起流行性性传播疾病及各种疾病综合征。衣原体在系统发生中属于唯一的真细菌分枝,与其他已知的微生物没有较近的关系,有其独特的分类系统(衣原体目(Chlamydiales)),只有一个科(衣原体科(Chlamydiaceae)),其中只有一个属(衣原体属(Chlamydia),也称为Chlamydophila)。衣原体的一个特殊的特征是其独特的生命周期,衣原体以两种不同的形态互相转换:细胞外感染形态(原生小体,EB)和细胞内非感染形态(网状体,RB)。RB重新组装成EB后完成一个生命周期,宿主细胞破裂,准备再感染其他细胞。
现在已知的衣原体有四种:沙眼衣原体(C.trachomatis)、肺炎衣原体(C.pneumoniae)、猫心衣原体(C.Pecorum)和鹦鹉热衣原体(C.psittaci){参考文献1,2},其基因组序列已知{参考文献3-9}。
沙眼衣原体的人类血清变种(“血清变型”)分为两个生物变种(“生物变型”)。血清变型A-K主要引起眼组织(A-C)或泌尿生殖道(D-K)的上皮感染。血清变性L1、L2和L3引起侵入性性病淋巴肉芽肿(LGV)。
虽然衣原体感染本身也可以致病,但是一般认为在某些病人中症状的严重性事实上是由于宿主体内的异常免疫应答。感染源不能被清除会产生持续的免疫刺激,其结果不是帮助宿主而是导致慢性感染,产生严重后果,如不孕和失明{10}。另外,对天然衣原体感染所产生的保护通常是不完全的、瞬时的和株特异性的。
由于这种疾病的严重性,因此迫切需要合适的疫苗。疫苗可用于(a)诱导抗衣原体感染的免疫或抗衣原体诱导疾病的免疫(预防性疫苗),或者(b)治疗已有的衣原体慢性感染(治疗性疫苗)。但是,由于衣原体是细胞内的寄生虫,因此通常情况下衣原体可以逃避抗体介导的免疫攻击。
沙眼衣原体的各种抗原蛋白都已被鉴定,其中细胞表面的蛋白是被研究的最多的靶位{如1,11}。其中包括pgp3{12、13、14}、MOMP{15}、Hsp60(GroEL){16}和Hsp70(DnaK样){17}。试验证明并不是所有的这些蛋白都能成为有效的疫苗,因此本发明的目的之一就是鉴定出能在自然感染时激发机体免疫应答的沙眼衣原体抗原以找到适于制造疫苗的抗原和免疫原。本发明的另一个目的是鉴定出可用于诊断沙眼衣原体的抗原。
本发明的详细描述
参考文献18描述了肺炎衣原体的各种蛋白质,根据经验这些蛋白是具有免疫活性的、免疫可影响的(immunoaccessible)和/或存在于原生小体内。蛋白的这些特性不是从其基因组序列信息中推导出来的。参考文献18中描述这些蛋白可用于治疗或预防衣原体引起的感染,特别是肺炎衣原体。由于存在种间交叉反应,肺炎衣原体的蛋白也可用于治疗或预防其他种的衣原体引起的感染。
通过比较全基因组序列发现肺炎衣原体与沙眼衣原体的亲缘关系很近。
本发明涉及参考文献18所描述的肺炎衣原体蛋白相应的沙眼衣原体蛋白(SEQIDs 1-261中奇数号的序列)。这些蛋白可用于治疗或预防衣原体引起的感染,特别是沙眼衣原体引起的感染。
特别优选的蛋白是那些以前被称为“假设蛋白”的蛋白质(见本文的表I)或那些以前被认为是位于胞浆中的蛋白质。
沙眼衣原体蛋白
本发明涉及含有一个或多个SEQ IDs 1-261中奇数号氨基酸序列的蛋白质。
本发明涉及的另外一些蛋白质含有与一个或多个奇数号氨基酸序列SEQ IDs 1-261至少有x%序列一致性的序列。根据不同的序列,x优选50%或更高(即60%,70%,80%,90%,95%,99%或更高)。一般来说,两个蛋白之间具有50%或更高的序列一致性就被认为是功能等价的。蛋白质之间的一致性优选用Smith-Waterman同源性搜索算法来确定,该算法被用在MPSRCH程序(Oxford Molecular)中,利用仿射缺口(affine gap)搜索,裂隙开放补偿参数为12,裂隙延伸补偿参数为1。
本发明还涉及含有奇数号氨基酸序列SEQ IDs 1-261片段的蛋白质。该片段应至少含有n个该序列上的连续氨基酸,根据不同的序列,n等于7或更高(即8、10、12、14、16、18、20、30、40、50、75、100、150、200或更高)。优选的片段含有该序列的一个或多个表位。其他优选的片段省略了信号肽。
本发明的蛋白质可以各种方法制造,如化学合成法(至少部分是通过化学合成的)、利用蛋白酶消化较长的多肽、从RNA中翻译、从细胞培养物中纯化(如从重组表达物中或从沙眼衣原体培养物中)等。大肠杆菌内的异源表达也是优选的制造途径。
本发明的蛋白质可以是各种形式的,如天然的、融合的、糖基化的、非糖基化的、脂质化的等。
本发明的蛋白质优选以实质纯化的形式制造(即基本不含沙眼衣原体的蛋白或宿主细胞的蛋白)。
本发明的蛋白可以连接到固相支持物上。还可以含有可检测的标记(如放射性的或荧光标记物,或生物素标记物)。
本发明的蛋白优选衣原体蛋白。
沙眼衣原体核酸
本发明涉及含有一个或多个SEQ IDs 2-262中偶数号核苷酸序列的蛋白。
本发明涉及的另外一些核酸含有与一个或多个偶数号核苷酸序列SEQ IDs 2-262至少有x%序列一致性的序列。根据不同的序列,x优选50%或更高(即60%、70%、80%、90%、95%、99%或更高)。
另外,本发明还涉及能与偶数号核苷酸序列SEQ IDs 2-262组成的核酸杂交的核酸。杂交反应可在不同“严谨性”的条件下进行。增加杂交反应条件的严谨性是大家所熟知的,并且已发表在文献中。相关的杂交条件(以严谨性不断增加的顺序)如下:孵育温度25℃、37℃、50℃、55℃和68℃;缓冲液浓度10×SSC、6×SSC、1×SSC、0.1×SSC以及其他缓冲系统等价的体系;甲酰胺浓度0%、25%、50%和75%;孵育时间从5分钟到24小时;1、2或更多洗涤步骤;洗涤孵育时间1、2或15分钟;洗涤溶液6×SSC、1×SSC、0.1×SSC或去离子水。在一些实施方式中,本发明的分离的核酸选择在低严谨性条件下杂交;在另外一些实施方式中,本发明的分离的核酸选择在中等严谨性条件下杂交;在另一些实施方式中,本发明的分离的核酸选择在高严谨性条件下杂交。低严谨性杂交条件的例子是50℃、10×SSC。中等严谨性杂交条件的例子是55℃、1×SSC。高严谨性杂交条件的例子是68℃、0.1×SSC。
本发明还涉及含有偶数号核苷酸序列SEQ IDs 2-262片段的核酸。该片段应至少含有n个沙眼衣原体序列上的连续核苷酸,根据不同的序列,n等于7或更高(即10、12、14、15、18、20、25、30、35、40、50、75、100、200、300或更高)。
本发明的另外一个方面涉及编码本发明蛋白和蛋白片段的核酸。
本发明涉及与上述核酸序列互补的核酸序列(如作为反义核酸或探针的序列)。
本发明的核酸可以通过许多途径制造,如化学合成(至少部分可通过化学方法合成)、用限制性内切酶消化较长的多聚核苷酸、从基因组文库或cDNA文库中钓取、或者从生物体内提取等。
本发明的核酸可以有各种形式(如单链、双链、线性、环状、载体、引物、探针等)。
本发明的核酸可以连接到固相支持物(小珠、平板、滤膜、胶片、波片、树脂等)上。本发明的核酸可以含有可检测的标记(如放射性的或荧光标记物,或生物素标记物)。这在用核酸检测技术检测多聚核苷酸时特别有用,如,以核酸为引物或探针用于PCR,LCR,TMA,NASBA,bDNA等。
本发明的核酸优选衣原体核酸。
术语“核酸”包括DNA、RNA、DNA/RNA杂合子以及DNA或RNA类似物,如那些含修饰骨架或碱基的核酸,以及肽核酸(PNA)等。
本发明的核酸可以实质纯化的形式被分离和制造,一般包括除了染色体外其他形式。通常来说,获得的多聚核苷酸基本不含其他天然的核酸序列,一般至少有约50%(重量百分比)的纯度,通常至少约90%的纯度。
核酸可用于制造多肽;作为探针检测生物样品中的核酸;制造更多的多聚核苷酸拷贝;制造核酶或反义寡核苷酸;以及作为单链DNA探针或三链形式的寡核苷酸等。
本发明涉及含本发明核酸序列的载体(即克隆载体或表达载体)以及该载体转化的宿主细胞。
组合物
本发明的另外一个方面涉及含有本发明蛋白质和/或核酸的组合物。这些组合物优选具有免疫原性的组合物,如疫苗,以及适于免疫和制造疫苗的组合物。本发明的疫苗可以是预防性的,也可以是治疗性的,一般来说这些组合物都含有能诱导抗体产生的抗原,该抗体能抑制(a)衣原体粘附,(b)衣原体进入,和/或(c)衣原体在宿主细胞内成功复制。疫苗优选能诱导任何细胞介导的T细胞反应,这是从宿主体内清除衣原体所必须的。
本发明还涉及根据本发明能用作药物(如作为疫苗)的核酸或蛋白质。
本发明还涉及根据本发明用核酸或蛋白制造药物(如疫苗或免疫原性组合物)以治疗或预防衣原体感染。一般来说是指沙眼衣原体,但是由于存在种内交叉反应,也可以是肺炎衣原体、猫心衣原体或鹦鹉热衣原体。对于预防来说,药物优选能激发衣原体EB形态特异性的免疫应答;对于治疗老说,药物优选能激发衣原体RB形态特异性的免疫应答。
本发明还涉及根据本发明利用核酸或蛋白质制造药物(如疫苗或免疫原性组合物)以中和沙眼衣原体原生小体。
本发明还涉及治疗(如免疫)患者(如人)的方法,该方法包括给予患者以有效治疗剂量的本发明的核酸或蛋白质。
本发明还涉及提高患者体内免疫应答的方法,该方法包括给予患者以免疫有效剂量的本发明的核酸或蛋白质。免疫应答包括诱导患者体内产生抗体和/或细胞免疫应答(如CTL反应)。免疫应答可以是EB或RB特异性的,或者宿主胞浆所表达的蛋白特性的。抗体反应优选EB特异性的,细胞免疫应答优选胞浆蛋白特异性的或RB蛋白特异性的。
本发明还涉及诱导机体产生能识别本发明蛋白的抗体的方法,该方法包括给予患者衣原体原生小体或网状体的步骤。抗体优选EB特异性的。
本发明还涉及中和沙眼衣原体感染的方法,该方法包括给予患者本发明的蛋白、核酸或抗体的步骤。该方法最好能中和EB感染。
本发明还涉及从生物样品中检测衣原体EB或RB的方法,该方法包括本发明的抗体与样品接触的步骤。样品可以是血样、其他体液或组织。该方法可用于诊断衣原体感染。
本发明的免疫原性组合物还可以包含下面的一种或多种抗原:
-幽门螺旋菌来源的蛋白,如VacA、CagA、NAP、HopX、HopY{见WO98/04702}和/或尿素酶。
-脑膜炎奈瑟球菌(N.meningitidis)血清型B来源的蛋白抗原,如WO99/24578、WO99/36544、WO99/57280、WO00/22430、Tettelin等,(2000)Science 287:1809-1815;Pizza等,(2000)Science 287:1816-1820和WO96/29412中所描述的,以及蛋白“287”及其特别优选的衍生物。
-脑膜炎奈瑟球菌血清型B来源的外膜小泡(OMV)制造物,如WO01/52885;Bjune等,(1991)Lancet 338(8775):1093-1096;Fukasawa等,(1999)Vaccine17:2951-2958;Rosenqvist等,(1998)Dev,Biol,Stand,92:323-333等文献所描述的。
-脑膜炎奈瑟球菌血清型A、C、W135和/或Y来源的糖类抗原,如Costantino等,(1992)Vaccine 10:691-698中所描述的血清型C来源的寡糖{也可参见Costantino等,(1999)Vaccine 17:1251-1263}。
-肺炎链球菌来源的糖类抗原,{见Watson(2000)Pediatr Infect Dis J 19:331-332;Rubin(2000)Pediatr Clin North Am 47:269-285,v;Jedrzejas(2001)Microbiol MolBiol Rev 65:187-207}。
-甲型肝炎病毒来源的抗原,如灭活病毒{见Bell(2000)Pediatr Infect Dis J19:1187-1188;Iwarson(1995)APMIS 103:321-326}。
-乙型肝炎病毒来源的抗原,如表面抗原或核心抗原{见Gerlich等,(1990)Vaccine & Suppl:S63-68和79-80}。
-丙型肝炎病毒来源的抗原{见Hsu等,(1999)Clin Liver Dis 3:901-915}。
-百日咳博德特氏菌来源的抗原,如百日咳海参毒素(PT)和丝状血凝素(filamentous haemagglutinin)(FHA),还可以选择性地与百日咳杆菌粘附素和/或凝集原2和3结合{见Gustafsson等,(1996)N,Engl,J.Med,334:349-355;Rappuoli等,(1991)TIBTECH9:232-238}。
-白喉抗原,如白喉类毒素{见《疫苗》(1988)第三章,编,Plotkin和Mortimer。ISBN 0-7216-1946-0},或CRM197突变株{见Del Guidice等,(1998)MolecularAspects of Medicine 19:1-70}。
-破伤风抗原,如破伤风类毒素{见Plotkin和Mortimer的第4章}。
-流感嗜血杆菌B来源的糖类抗原。
-淋病奈瑟氏球菌(N.gonorrhoeae)来源的抗原{见WO99/24578,WO99/36544,WO99/57280}。
-肺炎衣原体来源的抗原{见PCT/IB01/01445;Kalman等,(1999)NatureGenetics 21:385-389;Read等,(2000)Nucleic Acids Res 28:1397-406;Shirai等,(2000)J.Infect,Dis,181(Suppl 3):S524-S527;WO99/27105;WO00/27994;WO00/37494}。
-沙眼衣原体来源的抗原{见WO99/28475}。
-牙龈卟啉单胞菌(Porphyromonas gingivalis)来源的抗原{见Ross等,(2001)Vaccine 19:4135-4142}。
-脊髓灰质炎抗原{见Sutter等,(2000)Pediatr Clin North Am 47:287-308;Zimmerman和Spann(1999)Am Fam Physician 59:113-118,125-126}如IPV或OPV。
-狂犬病抗原{见Dreesen(1997)Vaccine 15 Suppl:S2-6},如冻干的灭活病毒{见MMWR Morb Mortal Wkly Rep 1998 Jan 16;47(1):12,19;RabAVertTM}。
-麻疹、流行性腮腺炎和/或风疹抗原{见Plotkin和Mortimer第9、10和11章}。
-流感抗原{见Plotkin和Mortimer第19章},如血凝集素和/或神经酰胺酶表面蛋白。
-粘膜炎莫拉菌来源的抗原{见McMichael(2000)Vaccine 19增补1:S101-107}。
-金黄色葡萄球菌来源的抗原{见Kuroda等,(2001)Lancet 357(9264):1225-1240;也见1218-1219页}。
-无乳链球菌来源的抗原{见WO02/34771}。
-酿脓链球菌(Streptococcus pyogenes)来源的抗原{见WO02/34771}。
如果这些抗原中包含糖链或碳水化合物成分,优选与载体蛋白连接以提高其免疫原性{见Ramsay等,(2001)Lancet 357(9251):195-196;Lindberg(1999)Vaccine 17增补2:S28-36;Conjugate Vaccines(Cruse等编)ISBN 3805549326,特别是10:48-114等}。优选的载体蛋白是细菌毒素或类毒素,乳白喉类毒素或破伤风类毒素。CRM197是特别优选的。其他适宜的载体蛋白包括脑膜炎奈瑟球菌外膜蛋白{见EP-0372501}、合成肽{见EP-0378881,EP-0427347}、热休克蛋白{见WO93/17712}、百日咳蛋白{见WO98/58668;EP-0471177}、流感病毒的蛋白D{见WO00/56360}、C,difficile的毒素A或B{见WO00/61761}等。任何适宜的连接反应都可以使用,必要时可以用任何适宜的连接子。
毒素蛋白抗原必要时可脱毒(如通过化学方法和/或基因工程方法使百日咳毒素脱毒)。
如果组合物中包含白喉抗原,那么最好也包含破伤风抗原和百日咳抗原,同样,如果组合物中包含破伤风抗原,那么最好也包含白喉抗原和百日咳抗原,如果组合物中包含百日咳抗原,那么最好也包含白喉抗原和破伤风抗原。
抗原最好可以吸附到铝盐上。
组合物中每种抗原的浓度一般至少为1μg/ml。一般来说,任何给定的抗原的浓度都要足以激发出抗该抗原的免疫应答。
本发明还涉及含有两种或多种本发明蛋白的组合物。
处理方法
本发明还涉及本发明蛋白的制造方法,该方法包括按照本发明培养宿主细胞的步骤,培养条件要能够诱导蛋白的表达。
本发明涉及制造本发明蛋白或核酸的方法,其中蛋白或核酸的部分或全长是通过化学方法合成的。
本发明涉及检测样品中沙眼衣原体的方法,其中包括使样品与本发明蛋白特异性的抗体接触的步骤。
下面概括描述了用于实现本发明的标准技术和方法(如利用所描述的序列进行免疫)。这种概括并不是对本发明的限制,而是举例说明可以使用的方法,但不是必须使用的。
概述
除非另外说明,实现本发明都是应用分子生物学、微生物学、重组DNA和免疫学的常规技术方法,这些方法都是本领域技术人员所熟知的。这些技术在文献中已有了详细的描述,如Sambrook《分子克隆:实验室手册》,第二版(1989)和第三版(2001);《DNA克隆》,I和ii卷(D,N Glover编,1985);《寡核苷酸合成》(M,J.Gait编,1984);《核酸杂交》(B,D,Hames和S,J.Higgins编,1984);《转录和翻译》(B,D,Hames和S,J.Higgins编,1984);《动物细胞培养》(R,I,Freshney编,1986);《固定化细胞和酶》(IRL Press,1986);B,Perbal,《分子克隆操作指南》(1984);《酶学方法》系列(Academic Press,INC.),特别是154和155卷;《哺乳动物细胞基因转移载体》(J.H,Miller和M,P,Calos编,1987,ColdSpring Harbor Laboratory);Mayer和Walker编(1987),《细胞生物学和分子生物学中的免疫化学方法》(Academic Press,London);Scopes(1987),《蛋白质纯化:原理和操作方法》,第二版(Springer-Verlag,N,Y,);以及《实验免疫学手册》I-IV卷(D,M,Weir和C,C,Blackwell编,1986)。
本说明书使用核苷酸和氨基酸的标准缩写。
定义
含有X的组合物中X的重量如果占X+Y总重量的85%以上则指该组合物“基本不含”Y。较好的是X占X+Y总重量的90%以上,更好的是95%、甚至99%以上。
术语“含有”可以指“包括”,也可以指“由……组成”,如,组合物“含有X”可以指只含有X,也可以指除了含X外还可以含有其他物质,如Y。
术语“异源的”是指在自然界中不会同时存在的两种生物组分。组分可以是宿主细胞、基因或调节区如启动子。尽管在自然界中异源组分不会同时存在,但是可以将他们连接起来,如可以将一个基因的启动子人工连接到另一个异源基因上。再比如衣原体序列对于鼠宿主细胞来说就是异源的。另外,可以将同一蛋白或不同蛋白的两个表位连接成一个蛋白,其排列方式与天然方式不同。
“复制起点”是指一种能起始和调节多聚核苷酸如表达载体复制的多聚核苷酸序列。复制起点在细胞内作为多聚核苷酸自主复制单位来发挥功能,并且在自身的控制下复制。复制起点是载体在特定宿主细胞内复制所必须的。具有特定复制起点的表达载体能在细胞内存在适当蛋白的情况下以高拷贝数增殖。复制起点的例子有在酵母中起作用的自主复制序列和在COS-7细胞内起作用的病毒T抗原。
“突变”序列被定义为一段DNA、RNA或氨基酸序列,该序列与天然的或描述的序列不同但又有一定的序列一致性。对于不同的序列来说,天然的或描述的序列与突变序列之间的序列一致性最好大于50%(如60%,70%,80%,90%,95%,99%或更高,这是根据上述的Smith-Waterman算法来计算的)。
如本文所描述,一个核酸分子或区的“等位基因突变株”是指这个核酸分子或区位于另一个或第二个分离株基因组相同的位点上,由于突变或重组二发生的自然突变使该序列与天然序列相似但不完全一致。等位基因突变株的编码区一般编码与其天然基因所编码的蛋白具有相似活性的蛋白。等位基因突变株也可以包含5’或3’非翻译区的改变,如调节控制区的改变(见美国专利5,753,235号)。
表达系统
衣原体核苷酸序列可在各种不同的表达系统内表达;例如,利用哺乳动物细胞、杆状病毒、植物、细菌和酵母的表达系统。
i.哺乳动物表达系统
哺乳动物表达系统使本领域所熟知的。哺乳动物启动子是指任何能与哺乳动物RNA多聚酶结合并能启动编码序列(即结构基因)下游(3’)转录子转录成mRNA的DNA序列。启动子具有通常位于编码序列的5’端的转录起始区和位于转录起始位点上有25-30bp处的TATA盒。TATA盒被认为可以指导RNA多聚酶II在正确的位点开始合成RNA。哺乳动物启动子还可以包含上游启动子元件,通常位于TATA盒上游200bp处。上游启动子元件决定了转录起始的速率,并且在两个方向上都能发挥作用{Sambrook等,(1989)“克隆基因在哺乳动物细胞内的表达”(″Expression ofCloned Genes in Mammalian Cells.″)《分子克隆:实验室手册》第二版(In Molecular Cloning:A Laboratory Manual,第二版)}。
哺乳动物病毒基因的表达水平一般很高并且具有广泛的宿主范围;因此编码哺乳动物病毒基因的序列具有特别有用的启动子序列。例如,SV40早期启动子、鼠乳头瘤病毒LTR启动子、腺病毒主要的晚期启动子(Ad MLP)和单纯疱疹病毒启动子。另外,非病毒基因来源的序列,如鼠金属硫蛋白基因,也具有很有用的启动子序列。基因的表达可以是组成性的,也可以是可调节的(可诱导的),在激素反应性细胞内可依赖启动子而被糖皮质激素诱导。
通常来说增强子元件(增强子)与上面所描述的启动子元件一起可以提高表达水平。当增强子与同源的或异源的启动子连接在一起时最多可以使转录水平提高1000倍,其合成是起始于正常的RNA起始位点。增强子位于转录起始位点的上游或下游,以正常的方向或相反方向,位于启动子远端1000bp以上都可以是有活性的{Maniatis等,(1987)Science 236:1237;Alberts等,(1989)《细胞分子生物学》第二版(Molecular Biology of the Cell,2nd ed.)}。来源于各种病毒的增强子元件是特别有用的,因为这些元件的宿主范围一般很宽。例如SV40早期基因的增强子{Dijkema等,(1985)EMBO J.4:761}和来源于劳氏肉瘤病毒{Gorman等,(1982)PNAS USA 79:6777}和人巨细胞病毒{Boshart等,(1985)Cell 41:521}长末端重复序列(LTR)来源的增强子/启动子。
另外,有些增强子是可调节的,只有在存在诱导子如激素或金属离子的条件下才有活性{Sassone-Corsi和Borelli(1986)Trends Genet,2:215;Maniatis等,(1987)Science 236:1237}。
DNA分子可在哺乳动物细胞内表达。启动子序列可以直接连接到DNA分子上,在这种情况下重组蛋白N端的第一个氨基酸一般都是蛋氨酸,这个氨基酸是由ATG起始密码子编码的。如果需要,蛋白的N端可以通过在体外与溴化氰共孵育而被切除。
通过制造编码融合蛋白的嵌合DNA分子可以使表达的外源蛋白从细胞中分泌到生长介质内,这种融合蛋白包含一个前导序列,该序列负责哺乳动物细胞内外源蛋白的分泌。在前导片段与外源基因之间最好有一个处理位点,这样在体内或体外都可以在该位点裂解蛋白。前导序列通常编码由疏水氨基酸组成的信号肽,该信号肽可以引导蛋白从细胞内分泌出来。腺病毒的一种分三部分的前导序列是一个很典型的例子,它可以使外源蛋白从哺乳动物细胞内分泌出来。
一般来说,能被哺乳动物细胞识别的转录终止子和多聚腺苷酸序列位于翻译终止密码子的3’端,因此和启动子一起位于编码序列的两侧。成熟mRNA的3’末端是通过位点特异性的转录后剪接和多聚腺苷酸化而形成的{Birnstiel等,(1985)Cell41:349;Proudfoot和Whitelaw(1988)“真核RNA终止子及3’末端的处理”,《转录和剪接》(″Termination and 3′end processing of eukaryotic RNA,In Transcription andsplicing)(B,D,Hames和D,M,Glover编);Proudfoot(1989)Trends,Biochem,Sci,14:105}。这些序列指导mRNA的转录,mRNA被翻译成DNA编码的多肽。转录终止子/多聚腺苷酸信号的例子包括那些SV40来源的{Sambrook等,(1989)“克隆基因在哺乳动物细胞内的表达”《分子克隆:实验室手册》}。
一般来说,上述元件,包括启动子、多聚腺苷酸信号和转录终止序列一起被放入表达载体内。如果需要增强子、内含子和前导序列也可以放入表达载体内,其中内含子是供体和受体的剪接位点。表达载体通常以复制子的形式存在,如染色体外元件(即质粒),能在宿主如哺乳动物细胞或细菌内稳定存在。哺乳动物复制系统包括那些来源于动物病毒的复制系统,这些系统需要反式作用因子才能复制。例如,含有乳头多瘤空泡病毒如SV40{Gluzman(1981)Cell 23:175}或多瘤病毒复制系统的质粒如果存在适当的病毒T抗原可以以极高的拷贝数复制。哺乳动物复制子的其他例子包括那些来源于牛乳头状瘤病毒和Epstein-Barr病毒的复制子。另外,复制子可以有两个复制系统,这样这种复制子就可以在哺乳动物细胞内用于表达,而在原核细胞内用于克隆和扩增。这种哺乳动物-细菌穿梭载体的例子包括pMT2{Kaufman等,(1989)Mol.Cell.Biol.9:946}和pHEBO{Shimizu等,(1986)Mol.Cell.Biol.6:1074}。
不同的宿主细胞可以采用不同的转化方法。将异源多聚核苷酸导入哺乳动物细胞的方法是本领域所熟知的,其中包括葡聚糖介导的转染、钙磷酸盐沉淀、多聚季胺介导的转染、原生质体融合、电穿孔、脂质体包裹多聚核苷酸、直接将DNA微注射到核内。
能用作宿主细胞进行表达的哺乳动物细胞系是本领域所熟知的,其中包括美国典型培养物收集中心(ATCC)的许多永生化的细胞系,包括而不限于中国仓鼠卵巢(CHO)细胞、HeLa细胞、婴儿仓鼠肾(BHK)细胞、猴肾细胞(COS)、人肝细胞癌细胞(即Hep G2)和其他细胞系相连接。
ii.杆状病毒系统
编码蛋白的多聚核苷酸也可以插入到适宜的昆虫细胞表达载体内,并与载体内适当的控制元件。载体构建所用的方法是本领域所熟知的。一般来说,表达系统的组分包括一个转移载体转移载体,通常是细菌质粒,质粒包含一个杆状病毒基因组片段和一个限制性酶切位点,限制性酶切位点便于插入外源基因或要表达的目的基因;表达系统的组分还包括一个序列与转移载体中杆状病毒特异性的片段同源的野生型杆状病毒(这样可以使外源基因与杆状病毒基因组发生同源重组),以及适当的昆虫宿主细胞和生长介质。
将编码蛋白的DNA序列插入到转移载体后,载体和野生型病毒基因组一起转染到昆虫宿主细胞内,载体和病毒基因组在其中发生重组。包装好的重组病毒得以表达,然后鉴定和纯化重组斑。杆状病毒/昆虫细胞表达系统的材料和方法都可以买到,一般是以试剂盒的形式,如Invitrogen,San Diego CA(″MaxBac″试剂盒)。这些方法是本领域技术人员所熟知的,在Summers和Smith,Texas AgriculturalExperiment Station Bulletin No,1555(1987)(本文以下称为″Summers和Smith″)中有详细描述。
在将编码蛋白的DNA序列插入到杆状病毒基因组内之前,上面所描述的元件,包括启动子、前导序列(如果需要)、目的编码序列和转录终止序列通常被装配到中间过渡载体(转移载体)内。这个载体可能含有与调节元件连接在一起的单个基因;与各自的调节序列连接在一起的多个基因;或者由同一组调节序列控制的多个基因。中间过渡载体一般位于一个复制子内,如染色体外的元件(即质粒),钙元件能在宿主如细菌内稳定存在。复制子含有一个复制系统,从而可以使其在适宜的宿主内克隆和扩增。
目前最常用的将外源基因导入AcNPV内的转移载体是pAc373。本领域所熟知的其他载体也可以使用。其中包括pVL985(该载体将多角体蛋白的起始密码子ATG改变成ATT,在ATT下游32bp处有一BamHI克隆位点,见Luckow和Summers,Virology(1989)17:31)。
质粒通常也含有多角体蛋白的多聚腺苷酸信号(Miller等,(1988)Ann,Rev,Microbiol.,42:177)和原核细胞的氨苄青霉素耐药(amp)基因以及用于在大肠杆菌内筛选和传播的复制起点。
杆状病毒转移载体通常含有杆状病毒启动子。杆状病毒启动子是能结合杆状病毒RNA多聚酶和能将编码序列(即结构基因)下游(5’到3’)起始转录成mRNA的任何DNA序列。启动子含有转录起始区,该起始区一般靠近编码序列的5’末端。这个转录起始区一般都含有RNA多聚酶结合位点和一个转录起始位点。杆状病毒转移载体还可以包含被称为增强子的第二区,该区一般位于结构基因的远端。表达可以是调节的,也可以是组成的。
结构基因在病毒感染周期的晚期大量转录,特别是有启动子序列时。结构基因的例子包括编码病毒多角体蛋白的基因Friesen等,(1986)“杆状病毒基因表达的调节”《杆状病毒分子生物学》(Walter Doerfler编);EPO Publ,Nos,127 839和155 476;以及编码p10蛋白的基因,Vlak等,(1988),J.Gen,Virol,69:765。
编码适宜信号序列的DNA可以来源于分泌的昆虫蛋白或杆状病毒蛋白基因,如杆状病毒多角体蛋白基因(Carbonell等,(1988)Gene,73:409)。另外,由于哺乳动物细胞翻译后修饰(如信号肽的剪切、蛋白裂解以及磷酸化)信号可被昆虫细胞识别,并且分泌和核积聚所需的信号在无脊椎动物细胞和脊椎动物细胞之间是高度保守的,因此非昆虫来源的前导序列如编码人α-干扰素基因(Maeda等,(1985),Nature315:592);人胃泌素释放肽基因(Lebacq-Verheyden等,(1988),Molec.Cell.Biol,8:3129);人IL-2基因(Smith等,(1985)Proc,Nat,Acad,Sci,USA,82:8404);鼠IL-3基因(Miyajima等,(1987)Gene 58:273);以及人葡糖脑苷脂酶基因(Martin等,(1988)DNA,7:99)也可用于在昆虫内的分泌。
重组多肽或多聚蛋白可以在细胞内表达,如果含有合适的调节序列,也可以是分泌型的。非融合的外源蛋白如果要达到高水平的表达通常需要异源基因,该异源基因较理想的是具有一个短前导序列,前导序列内含有位于ATG起始信号前端的适宜的翻译起始信号。如果需要,在体外通过与溴化氰共孵育可以将N端的蛋氨酸从成熟蛋白上切下。
另外,如果重组多聚蛋白或蛋白质不能自然地分泌,就可以通过制造嵌合DNA分子使其从昆虫细胞内分泌出来,嵌合DNA分子编码含有前导序列的融合蛋白,该前导序列可以使外源蛋白从昆虫细胞内分泌出来。前导序列片段通常编码由疏水氨基酸组成的信号肽,这种信号肽可以指导蛋白质定位到内质网上。
将DNA序列和/或编码蛋白表达产物前体的基因插入以后,通过共转染将转移载体的异源DNA和野生型杆状病毒基因组DNA导入到昆虫宿主细胞内。载体的启动子和转录终止序列一般包含杆状病毒基因组的一个2-5kb的片段。将异源DNA导入到杆状病毒指定位点的方法是本领域所熟知的(见上述Summers和Smith;Ju等,(1987);Smith等Mol.Cell.Biol.(1983)3:2156;以及Luckow和Summers(1989))。例如,通过同源双交换重组可以将一个片段插入到一个基因内;插入片段也可以被插入到指定杆状病毒基因的限制性酶切位点上(Miller等,(1989),Bioessays 4:91)。一个DNA序列如果被克隆到表达载体内的多角体蛋白基因的位置上,其5’和3’两侧就是多角体蛋白特异性的序列,位于多角体蛋白启动子的下游。
新形成的杆状病毒表达载体随后被包装成有感染性的重组杆状病毒。同源重组发生的频率很低(约1%到约5%之间);因此主要的病毒都产生在共转染野生型病毒时。这样就需要一种方法来鉴定重组病毒。表达系统的一个优点是通过肉眼观察就可以鉴别出重组病毒。多角体蛋白是由天然病毒产生的,在病毒感染的后期感染细胞核内该蛋白的表达水平很高。积聚的多角体蛋白形成封闭小体,小体内也包含包被颗粒。这些封闭小体最大可达15im,具有很高的折光性,因此外观很量,在光学显微镜下可以很容易地看到它们。感染重组病毒的细胞缺乏封闭小体。为了区别重组病毒和野生型病毒,利用本领域技术人员所熟知的方法将感染上清液铺到单层昆虫细胞上使之形成噬菌斑。换言之,就是在光学显微镜下观察噬菌斑从而判断存在封闭小体(说明是野生型病毒)或是不存在封闭小体(说明是重组病毒)。《微生物学的最新方法》(Ausubel等编)卷2,16.8(Supp,10,1990)(″Current Protocols inMicrobiology″Vol,2(Ausubel等编)at 16.8(Supp,10,1990));上述的Summers和Smith;Miller等,(1989)。
现已研制出能感染多种昆虫细胞的重组杆状病毒表达载体。例如能感染下列细胞的重组感染病毒:埃及伊蚊(Aedes aegypti)、苜蓿银纹夜蛾(Autographacalifornica)、家蚕(Bombyx mori)、黑腹果蝇(Drosophila melanogaster)、草地夜蛾(Spodoptera frugiperda)和粉纹夜蛾(Trichoplusia ni)(WO 89/046699;Carbonell等,(1985)J.Virol,56:153;Wright(1986)Nature 321:718;Smith等,(1983)Mol.Cell.Biol.3:2156;以及Fraser等(1989)In Vitro Cell,Dev,Biol,25:225)。
杆状病毒/表达系统内异源多肽的直接表达和融合表达所需要的细胞和细胞培养基都可以买到;细胞培养技术是本领域技术人员所熟知的。见上述的Summers和Smith。
经修饰的昆虫细胞可以在合适的营养介质中生长,其中的质粒可以稳定存在。如果表达产物的基因是在可诱导控制序列的控制之下,宿主细胞可以高密度生长,表达产物被诱导表达。另外,如果表达是组成性的,表达产物会不断地释放到培养基中,因此营养培养基需要不断更换以去除目的产物并且补充消耗掉的营养物质。产物可通过这样一些技术纯化,其中包括色谱技术,如HPLC、亲和层析、离子交换层析等;电泳技术;密度梯度离心技术;溶剂提取等。
如果合适的话,产物可进一步纯化以基本去除分泌到介质中的或由于昆虫细胞裂解而产生的昆虫蛋白,这样所得到的产物至少基本不含宿主碎片,如蛋白、脂质和多糖。
为了使蛋白表达,转化细胞来源的重组宿主细胞要在适当的条件下孵育,该条件可以使重组蛋白编码序列表达。所选择的宿主细胞不同培养条件也不同。但是,本领域的技术人员根据本领域已知的知识很容易确定这些条件。
iii.植物系统
本领域中已知有许多植物细胞培养物和完整的植物基因表达系统。植物细胞基因表达系统的例子包括专利US 5,693,506;US 5,659,122和US 5,608,143中所描述的那些。植物细胞培养物基因表达的其他例子见Zenk,Phytochemistry 30:3861-3863(1991)的描述。除了上面所描述的参考文献以外,在下列参考文献中也有植物蛋白信号肽的描述:Vaulcombe等,Mol.Gen.Genet.209:33-40(1987);Chandler等,PlantMolecular Biology 3:407-418(1984);Rogers,J Biol,Chem,260:3731-3738(1985);Rothstein等,Gene 55:353-356(1987);Whittier等,Nucleic Acids Research 15:2515-2535(1987);Wirsel等,Molecular Microbiology 3:3-14(1989);Yu等,Gene 122:247-253(1992)。下列文献描述了植物激素对植物基因表达的调节、赤霉酸及赤霉酸所诱导的分泌酶:R,L,Jones和J,MacMillin,“赤霉素”《高级植物生理学》,MalcolmB,Wilkins编,1984,Pitman Publishing Limited,London,21-52页。描述其他代谢调节基因的文献有:Sheen,Plant Cell,2:1027-1038(1990);Maas等,EMBO J.9:3447-3452(1990);Benkel和Hickey,Proc.Natl.Acad.Sci.84:1337-1339(1987)。
通常利用本领域熟知的技术将所需的多聚核苷酸序列插入到表达盒中,该表达盒含有适于在植物内其作用的基因调节序列。将表达盒插入到理想的表达载体内,该载体在表达盒的上游和下游含有适于在植物宿主内表达的伴随序列。伴随序列可以来源于质粒,也可以来源于病毒,该序列赋予载体一些必须的功能,这些功能可以使载体从其来源克隆宿主如细菌内将DNA转移到植物宿主中。基本的细菌/植物载体构建最好能有一个较宽的宿主范围,如用于转化土壤杆菌的原核复制起点和原核筛选标记,土壤杆菌接到的植物转移所需的T DNA序列。如果异源基因不易于检测,载体内最好携带适于确定植物细胞是否被转化的筛选标记基因。文献Wilmink和Dons,1993,Plant Mol,Biol,Reptr,11(2):165-185中综述了合适的标记基因,例如筛选草家族成员的标记。
本文也涉及适用于将异源序列整合到植物基因组中的序列。这些序列包括用于同源重组的转座子序列和使异源表达盒随机整合到植物基因组中的Ti序列。适宜的原核筛选标记包括抗生素如氨苄青霉素或四环素耐药标记。编码其他功能的DNA序列也可以插入到载体内,如本领域所熟知的那样。
本发明所涉及的核酸分子可以包含在表达盒内用于表达目的蛋白。一般来说一个载体只含有一个表达盒,但是两个或多个也是可以的。重组表达盒除了含有异源蛋白编码序列外还可以包含如下元件:启动子区、植物5’非翻译区、根据结构基因有无起始密码子而添加的起始密码子以及翻译终止序列。表达盒5’末端和3’末端的独特限制性酶切位点便于将序列插入到载体内。
异源编码序列可以编码本发明有关的任何蛋白。编码本发明蛋白的序列编码蛋白适当加工和转运的信号肽,但是一般都缺少使目的蛋白与膜结合的序列。因此,大多数情况下,转录起始区都是为了一种基因,该基因在出芽时表达和易位(借助用于易位的信号肽),转录起始区也可使感兴趣的蛋白质易位,目的蛋白以这种方式从其表达的细胞内转运出来,从而被有效地收获。一般来说,种子内分泌的蛋白是穿过糊粉上皮(aleurone epithelium)或盾片状上皮进入种子的胚乳。这时不需要蛋白从其所产生的细胞内分泌出来,这有利于重组蛋白的分离和纯化。
如果目的基因的产物最终是在真核细胞内表达的,就需要确定克隆基因内是否含有被宿主剪接体作为内含子剪切掉的序列。如果有,那么可以在“内含子”区进行位点特异性的突变以防止这部分基因信息被错误地当作内含子密码被切除,Reed和Maniatis,Cell 41:95-105,1985。
载体可以用微注射器直接注射到植物细胞内。Crossway,Mol,Gen,Genet,202:179-185,1985。遗传物质也可以用聚乙烯甘油转移到植物细胞内,Krens等,Nature,296,72-74,1982。其他的核酸片段导入方法有小颗粒的高速弹道渗透,小颗粒内小珠或粒子的基质内或小颗粒的表面带有核酸,Klein等,Nature,327,70-73,1987以及Knudsen和Muller,1991,Planta,185:330-336,其中描述了颗粒轰击大麦胚乳制造转基因大麦的方法。其他基因导入的方法有原生质体与其他植物实体如小细胞、细胞、溶酶体或其他可融合的脂质表面小体融合,Fraley等,Proc.Natl.Acad.Sci.USA,79,1859-1863,1982。
载体也可以通过电穿孔导入到植物细胞内(Fromm等Proc.Natl.Acad.Sci.USA82:5824,1985)。这种方法是在含目的基因的质粒存在的情况下电穿孔植物原生质体。高频电子脉冲可使生物膜反向渗透从而允许质粒进入。经电穿孔的植物原生质体从新形成细胞壁,分裂并形成植物胼胝体。
所有能分离出原生质体并培养成完整再生植物的植物都可以用本发明的方法转化,这样就可以复原包含转移基因的植物。现在已知道所有的植物都可以从培养的细胞或组织中再生,包括而不限于所有主要种类的甘蔗、甜菜、棉花、水果或其他树种、荚果以及蔬菜。例如,某些适宜的植物有下列属的物种:草莓属、百脉根属、苜蓿属、红豆草(Onobrychis)、红花草属、葫芦巴属、豇豆、柑桔属、亚麻属、老鹳草属、木薯属、胡萝卜属、阿布属、芸苔属、萝卡属、芥子属、茄属、辣椒属、曼陀罗属、天仙子属、番茄属、烟草属、茄属、牵牛花属、毛地黄属、Maiorana、菊苣属、向日葵属、莴苣属、Bromus、天冬属、金鱼草属、Hererocallis、龙面花(Nemesia)、天竺葵属、黍属、狼尾草属、毛茛属、千里光属、喇叭舌属、香瓜属、Browaalia,大豆属、黑麦草属、玉蜀黍属、小麦属、高梁属以及曼陀罗属。
植物的再生方式因其种类不同而不同,但是,通常首先要得到含异源基因拷贝的转化原生质体悬液。胼胝体组织形成后要诱导其发芽,然后生根。另外,也可以从原生质体悬液中诱导胚胎形成。这些胚胎会如天然胚胎一样发育成植物。培养基内通常含有各种氨基酸和激素,如植物生长激素和细胞激肽。如果在培养基内加入谷氨酸和脯氨酸就更好,特别是对于玉米和苜蓿这类植物。发芽和生根常常同时发生。植物的有效再生以来于培养介质、植物的基因型以及培养过程。如果这三个因素都可以控制,那么再生完全可以被重复。
在某些植物细胞培养系统中,本发明的目的蛋白可以是分泌出来的,也可以从全植物中提取。如果本发明的目的蛋白分泌到培养介质中,就可以收集这些蛋白。另外,也可以将胚和除去一半胚的种子或其他植物组织机械磨碎使其释放出细胞和组织中的分泌蛋白。混合物悬浮于缓冲液中使可溶性蛋白复性。然后用常规的蛋白分离和纯化方法纯化重组蛋白。常规方法中的时间、温度、pH、氧气以及体积等参数可以调整以优化异源蛋白的表达和回收。
iv.细菌系统
细菌表达技术是本领域所熟知的。细菌启动子是指任何能与细菌RNA多聚酶结合并能启动编码序列(即结构基因)下游(3’)转录子转录成mRNA的DNA序列。启动子具有位于靠近编码序列的5’端的转录起始区。这个转录起始区通常包含一个RNA多聚酶结合位点和一个转录起始位点。细菌启动子还可以含有被称为操作子的第二区,该区与临近的RNA多聚酶结合位点重叠,RNA合成在此开始。
操作子可对转录进行负调节(可诱导的),例如,基因抑制蛋白可以结合到操作子上从而抑制特定基因的转录。组成性的表达可以不需要负性调节元件如操作子。另外,正性调节可由基因活化蛋白结合序列来完成,该序列如果存在一般靠近(5’)RNA多聚酶结合序列。基因活化蛋白的例子包括分解代谢活化蛋白(CAP),它可以辅助大肠杆菌内的lac操作子的转录起始{Raibaud等,(1984)Annu,Rev,Genet,18:173}。因此,表达的调节可以是正性的,也可以是负性的,从而增强或降低转录水平。
编码代谢通路中酶的序列具有特别有用的启动子序列。例如,来源于糖代谢酶如半乳糖、乳糖(lac){Chang等,(1977)Nature 198:1056}和麦芽糖的启动子序列。其他的例子包括来源于生物合成酶如色氨酸(TRP)合成酶的启动子序列{Goeddel等,(1980)Nuc,Acids Res,8:4057;Yelverton等,(1981)Nucl,Acids Res,9:731;美国专利4,738,921;EP-A-0036776和EP-A-0121775}。g-laotamase(bla)启动子系统{Weissmann(1981)″The cloning of interferon and other mistakes.″引自Interferon3(I,Gresser编)},噬菌体λPL{Shimatake等,(1981)Nature 292:128}和T5{美国专利4,689,406}启动子系统也是有用的启动子序列。
另外,自然界中不存在的合成启动子也可以用作细菌启动子。例如,一种细菌和噬菌体的转录活化序列与另一种细菌和噬菌体的操作子序列相连接就形成了一种杂合的合成启动子{美国专利4,551,433}。例如,tac启动子就是trp-lac启动子的杂合产物,是由trp启动子和lac操纵子序列组成的,受lac抑制因子的调节{Amann等,(1983)Gene 25:167;de Boer等,(1983)Proc.Natl.Acad.Sci.80:21}。另外,细菌启动子还包括非细菌来源的天然启动子,这些启动子能与细菌RNA多聚酶结合并启动转录。非细菌来源的天然启动子还可以与相匹配的RNA聚合酶结合使某些基因在原核细胞内高水平表达。噬菌体T7 RNA聚合酶/启动子系统就是一个耦合启动子系统的例子{Studier等,(1986)J Mol,Biol,189:113;Tabor等,(1985)ProcNatl,Acad,Sci,82:1074}。另外,杂合启动子也可以由噬菌体启动子和大肠杆菌操纵子区组成(EPO-A-0 267 851)。
除了功能性的启动子序列之外,外源基因在原核细胞内的表达还需要有效的核糖体结合位点。大肠杆菌内的核糖体结合位点被称为Shine-Dalgarno(SD)序列,其中包含一个起始密码子(ATG)和一个位于起始密码子上游3-11bp处长度为3-9bp的序列{Shine等,(1975)Nature 254:34}。SD序列被认为是通过SD序列与大肠杆菌16S rRNA 3’端碱基配对而促进mRNA与核糖体的结合。{Steitz等,(1979)”mRNA中的遗传信号和核苷酸序列“《生物学调节和发育:基因表达》(R,F,Goldberger编)(″Genetic signals and nucleotide sequences in messenger RNA.″In BiologicalRegulation and Development:Gene Expression(R,F,Goldberger编))}。用弱核糖体结合位点表达真核基因和原核基因{Sambrook等,(1989)“大肠杆菌内克隆基因的表达”《分子克隆:实验室手册》}。
DNA分子可在细胞内表达。启动子序列可与DNA分子直接相连,这种情况下N端的第一个氨基酸一般都是蛋氨酸,是由起始密码子ATG编码。如果需要,N端的蛋氨酸可以通过在体外与溴化氰共孵育从蛋白上切下,或者通过在体内或体外与细菌蛋氨酸N端肽酶共孵育从蛋白上切下(EPO-A-0 219 237)。
除了直接表达以外还可以以融合蛋白的形式表达。一般都是将编码内源性细菌蛋白或其他稳定蛋白N端部分的DNA序列与异源编码序列的5’末端融合。这种载体表达以后就可以得到两种氨基酸序列融合的蛋白。例如,噬菌体λ细胞基因与外源基因的5’末端连接后在细菌内表达。
所得到的融合蛋白最好保留一个酶(因子Xa)作用位点以便从融合蛋白上切去噬菌体蛋白{Nagai等,(1984)Nature 309:810}。融合蛋白也可以从lacZ{Jia等,(1987)Gene 60:197}、trpE{Allen等1987}J.Biotechnol,5:93;Makoff等,(1989)J.Gen.Microbiol.135:11}和Chey{EP-A-0 324 647}基因来源的序列制造。两个氨基酸序列连接处的DNA序列可以编码剪接位点也可以不编码剪接位点。另外一个例子是泛素蛋白。这种融合蛋白是用泛素区序列制造的,该区内最好保留酶作用位点(即泛素特异性加工酶)以便于从融合蛋白上将泛素切下。通过这种方法可以分离出天然外源蛋白{Miller等,(1989)Bio/Technology 7:698}。
另外,外源蛋白也可以通过制造编码融合蛋白的嵌合DNA分子来使其从细胞内分泌出来,融合蛋白含有使外源蛋白从细菌内分泌出来的信号肽序列{美国专利4,336,336}。信号序列片段通常编码由疏水氨基酸组成的信号肽,该信号肽能引导蛋白从细胞内分泌出来。蛋白或者分泌到生长介质中(革兰氏阳性细菌),或者分泌到位于细胞内外膜之间的壁膜间隙内(革兰氏阴性细菌)。嵌合DNA分子最好含有加工位点,这样不论体内还是体外信号肽片段与外源基因之间都可以被切开。
编码适宜信号序列的DNA可以来源于细菌分泌蛋白的基因,如大肠杆菌外膜蛋白基因(ompA){Masui等,(1983),《基因表达的实验操作》;Ghrayeb等,(1984)EMBO J.3:2437}和大肠杆菌碱性磷酸酶信号序列(phoA){Oka等,(1985)Proc.Natl.Acad.Sci.82:7212}。信号序列的其他例子有各种杆菌的α-淀粉酶来源的信号序列,这些信号序列可用于使外源蛋白从B,subtilis中分泌{Palva等,(1982)Proc.Natl.Acad.Sci.USA 79:5582;EP-A-0 244 042}。
一般来说,细菌所识别的转录终止序列是位于翻译终止密码子3’端的调节区,因此它和启动子分别位于编码序列的两侧。这些序列可以指导mRNA的转录,mRNA翻译成DNA编码的多肽。转录终止序列一般为约50bp的DNA序列,能形成柄状的环,帮助转录终止。转录终止序列的例子有来源于具有强启动子的基因如大肠杆菌的trp基因和其他生物合成基因的转录终止序列。
上述的元件,包括启动子、信号序列(如果需要)、目的基因编码序列以及转录终止序列一般都被一起放入表达构建物内,表达构建物一般位于复制子内,例如能在宿主如细菌内稳定存活的染色体外元件(即质粒)。复制子含有一个复制系统,因此可以在原核宿主内存活用于表达或克隆和扩增。另外,复制子可以是高拷贝数目的质粒,也可以是低拷贝数目的质粒,高拷贝数目的质粒一般的拷贝数约在5到200之间,大多数约在20到150之间。含有高拷贝数目质粒的宿主优选至少含有约10个质粒,更优选的是至少约含20个质粒。高低数目拷贝载体的选择要根据载体和外源蛋白在宿主内的效应。
另外,利用整合载体可以将表达构建物整合到细菌基因组中。整合载体一般至少含有一个与细菌染色体同源的序列而使载体整合。整合是载体与细菌染色体之间同源序列重组的结果。例如,具有各种杆菌来源的DNA的整合载体可以整合到杆菌染色体内(EP-A-0 127 328)。整合载体也可以含有噬菌体序列或转座子序列。
一般来说,染色体外的整合表达构建物都含有筛选标记以便于筛选转化的细菌克隆。筛选标记可在细菌宿主内表达,含有使细菌对药物如氨苄青霉素、氯霉素、红霉素、卡那霉素(新霉素)和四环素耐药的基因{Davies等,(1978)Annu,Rev,Microbiol,32:469}。筛选标记还可以包括生物合成基因,如组氨酸、色氨酸和亮氨酸生物合成通路中的基因。
另外,上面所描述的组分中有些也被一起放入到转化载体内。转化载体通常都含有筛选标记,筛选标记存在于复制子内或如上面所述的位于整合载体内。
表达和转化载体或者作为染色体外复制子或者作为整合载体被研制出来用于转化到多种细菌中。例如,用于转化下列细菌的表达载体:枯草芽孢杆菌{Palva等,(1982)Proc.Natl.Acad.Sci.USA 79:5582;EP-A-0 036 259和EP-A-0 063 953;WO84/04541},大肠杆菌{Shimatake等,(1981)Nature 292:128;Amann等,(1985)Gene40:183;Studier等,(1986)J.Mol,Biol,189:113;EP-A-0 036 776,EP-A-0 136 829和EP-A-0 136 907},Streptococcus cremoris{Powell等,(1988)Appl,Environ,Microbiol,54:655};Streptococcus lividans{Powell等,(1988)Appl,Environ,Microbiol,54:655},Streptomyces lividans{美国专利4,745,056}。
将外源DNA导入到细菌宿主内的方法是本领域所熟知的,通常所用的方法是用CaCl2或其他试剂如二价阳离子和DMSO处理细菌使其转化。DNA也可以通过电穿孔导入到细菌中。不同的细菌种类选用不同的转化方法。见{Masson等,(1989)FEMS Microbiol,Lett,60:273;Palva等,(1982)Proc.Natl.Acad.Sci.USA 79:5582;EP-A-0 036 259和EP-A-0 063 953;WO 84/04541,杆菌属},{Miller等,(1988)Proc.Natl.Acad.Sci.85:856;Wang等,(1990)J Bacteriol.172:949,弯曲杆菌属},{Cohen等,(1973)Proc.Natl.Acad.Sci.69:2110;Dower等,(1988)Nucleic Acids Res,16:6127;Kushner(1978)“一种用ColE1来源的质粒转化大肠杆菌的改进方法”《基因工程:基因工程国际论坛论文集》,(H,W,Boyer和S,Nicosia编);Mandel等,(1970)J.Mol,Biol,53:159;Taketo(1988)Biochim.Biophys.Acta 949:318;大肠杆菌属},{Chassy等,(1987)FEMS Microbiol,Lett,44:173乳酸杆菌属};{Fiedler等,(1988)Anal,Biochem 170:38,假单孢菌属};{Augustin等,(1990)FEMS Microbiol,Lett,66:203,葡萄球菌属},{Barany等,(1980)J.Bacteriol.144:698;Harlander(1987)“电穿孔方法转化乳酸链球菌”《链球菌遗传学》(J,Ferretti和R,Curtiss III编);Perry等,(1981)Infect,Immun,32:1295;Powell等,(1988)Appl,Environ,Microbiol,54:655;Somkuti等,(1987)Proc,4th Evr,Cong,Biotechnology 1:412,链球菌属}。
v.酵母表达
酵母表达系统也是本领域普通技术人员所熟知的。酵母启动子是指任何能与酵母RNA多聚酶结合并能启动编码序列(即结构基因)下游(3’)转录子转录成mRNA的DNA序列。启动子具有位于靠近编码序列的5’端的转录起始区。这个转录起始区通常包含一个RNA多聚酶结合位点(“TATA盒”)和一个转录起始位点。酵母启动子还可以含有被称为上游活化序列(UAS)的第二区,该区如果存在一般位于结构基因的远端。UAS的存在使表达称为可调控的(可诱导的)。UAS布存在时发生组成性的表达。表达的调节可以是正性的,也可以是负性的,因此可以增强转录也可以抑制转录。
酵母是具有活性代谢途径的发酵微生物,因此编码代谢通路中的酶的序列具有特别有用的启动子序列。例如,乙醇脱氢酶(ADH)(EP-A-0 284 044)、烯醇化酶、葡糖激酶、葡萄糖-6-磷酸异构酶、甘油醛-3-磷酸脱氢酶(GAP或GAPDH)、己糖激酶、磷酸果糖激酶、3-磷酸甘油变位酶和丙酮酸激酶(PyK)(EPO-A-0 329 203)。编码酸性磷酸酶的酵母PHO5基因也含有有用的启动子序列{Myanohara等,(1983)Proc.Natl.Acad.Sci.USA 80:1}。
另外,自然界中不存在的合成启动子也可以作为酵母启动子。例如,一种酵母启动子的UAS序列可以与另一种酵母启动子的转录活化区相连接形成杂合的合成启动子。这种杂合启动子的例子包括与GAP转录活化区相连接的ADH调节序列(美国专利Nos,4,876,197和4,880,734)。其他杂合启动子的例子包括由ADH2、GAL4、GAL10或PHO5基因的调节序列与糖分解酶基因如GAP或PyK(EP-A-0 164 556)的转录活化区组合成的启动子。另外,酵母启动子也包括非酵母来源的能与酵母RNA聚合酶结合并启动转录的天然启动子。这种启动子的例子包括下列文献中所描述的那些{Cohen等,(1980)Proc.Natl.Acad.Sci.USA 77:1078;Henikoff等,(1981)Nature 283:835;Hollenberg等,(1981)Curr,Topics Microbiol,Immunol,96:119;Hollenberg等,(1979)“细菌抗生素耐药基因在酿酒酵母中的表达”《质粒在医疗、环境和商业领域的重要性》(K,N,Timmis和A,Puhler编);Mercerau-Puigalon等,(1980)Gene 11:163;Panthier等,(1980)Curr.Genet.2:109;}。
DNA分子可在酵母细胞内表达。启动子序列可与DNA分子直接相连,这种情况下N端的第一个氨基酸一般都是蛋氨酸,是由起始密码子ATG编码。如果需要,N端的蛋氨酸可以通过在体外与溴化氰共孵育从蛋白上切下。
融合蛋白是蛋白在酵母表达系统中表达的另外一种形式,就象在哺乳动物细胞表达系统、杆状病毒表达系统、和细菌表达系统一样。一般都是将编码内源性酵母蛋白或其他稳定蛋白N端部分的DNA序列与异源编码序列的5’末端融合。例如,酵母或人的超氧化物歧化酶(SOD)基因可连接到外源基因的5’端并在酵母中表达。两个氨基酸序列连接处的DNA序列可以编码裂解位点,也可以不编码,见EP-A-0 196 056。另外一个例子是泛素融合蛋白。这种融合蛋白是用泛素区序列制造的,该区内最好保留酶作用位点(即泛素特异性加工酶)以便于从外源蛋白上将泛素切下。通过这种方法可以分离出天然外源蛋白(见WO88/024066)。
另外,外源蛋白也可以通过制造编码融合蛋白的嵌合DNA分子使其从细胞内分泌到生长介质中,融合蛋白含有使外源蛋白从酵母内分泌出来的前导序列片段。前导序列片段与外源基因之间最好含有一个加工位点以便于在体内或体外将外源蛋白切下。前导序列片段通常编码由疏水氨基酸组成的信号肽,该信号肽能引导蛋白从细胞内分泌出来。
编码适宜信号序列的DNA分子可以来源于酵母分泌蛋白的基因,如转化酶的基因(EP-A-0012873;JPO 62,096,086)和A-因子(美国专利4,588,684)。另外,非酵母来源的前导序列如干扰素的前导序列也可用于酵母中(EP-A-0060057)。
一类优选的分泌前导序列是那些利用酵母α-因子基因片段的前导序列,该片段中含有一个″pre″信号序列和一个″pro″区。这类α-因子片段可以包含全长的pre-proα-因子前导序列(约含83个氨基酸残基),也可以包含截短的α-因子前导序列(通常约25到50个氨基酸残基)(美国专利4,546,083和4,870,008;EP-A-0 324 274)。其他利用α-因子前导序列片段提供分泌的前导序列包括杂合的α-因子前导序列,该序列是由一种酵母的原序列与另一种酵母α-因子的pro区杂合而成的(见WO89/02463.)。一般来说,酵母所识别的转录终止序列是位于翻译终止密码子3’端的调节区,和启动子一起分别位于编码序列的两侧。这些序列指导mR NA的转录,后者翻译成DNA编码的多肽。转录终止子序列和酵母所识别的其他终止子序列包括编码糖分解酶的那些基因来源的序列。
上述的元件,包括启动子、前导序列(如果需要)、目的基因编码序列以及转录终止序列一般都被一起放入表达构建物内,表达构建物一般位于复制子内,例如能在宿主如酵母或细菌内稳定存活的染色体外元件(即质粒)。复制子含有两个复制系统,因此可以在酵母内存活用于表达,在原核宿主内存活用于克隆和扩增。这种酵母-细菌穿梭载体的例子包括YEp24{Bostein等,(1979)Gene 8:17-24},pC1/1{Brake等,(1984)Proc.Natl.Acad.Sci USA 81:4642-4646},和YRp17{Stinchcomb等,(1982)JMol,Biol,158:157}。另外,复制子可以是高拷贝数目的质粒,也可以是低拷贝数目的质粒,高拷贝数目的质粒一般的拷贝数约在5到200之间,大多数约在10到150之间。含有高拷贝数目质粒的宿主优选至少含有约10个质粒,更优选的是至少约含20个质粒。高低数目拷贝载体的选择要根据载体和外源蛋白在宿主内的效应。见上述的Brake等。
另外,利用整合载体可以将表达构建物整合到酵母基因组中。整合载体一般至少含有一个与酵母染色体同源的序列而使载体整合,优选的是含有两个位于表达构建物两侧的同源序列。整合是载体与酵母染色体之间同源序列重组的结果{Orr-Weaver等,(1983)Methods in Enzymol,101:228-245}。整合载体可以通过载体内适当的同源序列直接整合到酵母基因组特异性的位点上。见上述Orr-Weaver等。整合可以是一个或多个表达构建物,可能会影响重组蛋白的表达水平{Rine等,(1983)Proc.Natl.Acad.Sci.USA 80:6750}。载体内的染色体序列可能是一个片段,这是由于整个载体的整合形成的,也可能是与染色体上相邻片段同源的两个片段,分别位于载体内表达构建物的两侧,这样就只有表达构建物可以稳定整合。
染色体外的整合表达表达构建物一般都含有筛选标记,用于筛选转化的酵母克隆。筛选标记包括酵母宿主内表达的生物合成基因,如ADE2、His4、LEU2、TRP1和ALG7,以及G418耐药基因,分别使酵母细胞对衣霉素和418耐药。另外,适宜的筛选标记还可以是能使酵母在毒性化合物如金属存在的条件下生长的基因。例如,CUP1就可以使酵母能在铜离子存在的条件下生长{Butt等,(1987)Microbiol.Rev.51:351}。
另外,上述的某些元件可以一起放入到转化载体中。转化载体通常含有筛选标记,如上所述筛选标记位于复制子内或整合载体内。
表达和转化载体或者以染色体外复制子的形式,或者以整合载体的形式,以被用于转化多种酵母。例如,表达载体可用于转化下列酵母:白色念珠菌{Kurtz等,(1986)Mol.Cell.Biol.6:142},Candida maltosa{Kunze,等,(1985)J.Basic Microbiol,25:141},多形汉森酵母{Gleeson等,(1986)J.Gen.Microbiol.132:3459;Roggenkamp等,(1986)Mol.Gen.Genet.202:302};脆壁克鲁维酵母{Das等,(1984)J.Bacteriol.158:1165},Kluyveromyces lactis{De Louvencourt等,(1983)J.Bacteriol.154:737;Van den Berg等,(1990)Bio/Technology 8:135},Pichia guillerimondii{Kunze等,(1985)J Basic Microbiol,25:141},Pichia pastoris{Cregg等,(1985)Mol.Cell.Biol.5:3376;美国专利Nos,4,837,148和4,929,555},酿酒酵母{Hinnen等,(1978)Proc.Natl.Acad.Sci.USA 75:1929;Ito等,(1983)J Bacteriol,153:163},稷酒裂殖酵母{Beach和Nurse(1981)Nature 300:706},以及Yarrowia lipolytica{Davidow等,(1985)Curr.Genet.10:380471 Gaillardin等,(1985)Curr,Genet.10:49}。
将外源DNA导入酵母宿主的方法是本领域所熟知的,通常包括转化原生质球或转化经碱性阳离子处理的完整酵母细胞。不同种类的酵母采用不同的转化方法。见{Kurtz等,(1986)Mol.Cell.Biol.6:142;Kunze等,(1985)J.Basic Microbiol,25:141;念珠菌属};{Gleeson等,(1986)J.Gen.Microbiol.132:3459;Roggenkamp等,(1986)Mol.Gen.Genet.202:302;汉森酵母属};{Das等,(1984)J.Bacterol,158:1165;DeLouvencourt等,(1983)J Bacteriol 154:1165;Van den Berg等,(1990)Bio/Technology8:135;克鲁维酵母属};{Cregg等,(1985)Mol.Cell.Biol.5:3376;Kunze等,(1985)J.Basic Microbiol,25:141;美国专利4,837,148和4,929,555;毕赤酵母属};{Hinnen等,(1978)Proc.Natl.Acad.Sci.USA 75;1929;Ito等,(1983)J.Bacteriol.153:163酵母属};{Beach和Nurse(1981)Nature 300:706;裂殖酵母属};{Davidow等,(1985)Curr.Genet.10:39;Gaillardin等,(1985)Curr.Genet.10:49;Yarrowia}。
药用组合物
药用组合物可以含有本发明的多肽和/或核酸。药用组合物含有治疗有效量的本发明权利要求所述的多肽、抗体或多聚核苷酸。
本文所用的术语“治疗有效量”是指治疗药物的剂量可以治疗、改善或预防特定的疾病或状态,或者具有可检测的治疗或预防效果。例如,效果可以通过化学标记或抗原水平来检测。治疗效果也包括生理体征的减轻,如体温降低。具体到每个个体所需的精确有效治疗剂量则要根据患者的体重和健康状况、疾病的性质和严重程度以及治疗方案或联合使用的药物来确定。因此,预先确定准确的有效量是没有必要的。但是,根据常规试验可以确定特定状况所需的有效剂量,临床医生可以作出判断。
本发明的有效剂量为每个个体给予约0.01mg/kg到50mg/kg或0.05mg/kg到10mg/kg DNA构建物。
药用组合物也可以包含药用载体。术语“药用载体”是指注射治疗药物如抗体、多肽、基因或其他治疗药物时所需的载体。这个术语是指其自身不能诱导产生对接受组合物的个体有害的抗体以及注射后无任何特殊毒性的任何药用载体。适宜的载体可以是大的、代谢较慢的大分子,如蛋白质、多糖、聚乳酸、聚乙醇酸、多聚氨基酸、氨基酸共聚物以及无活性的病毒颗粒。这些载体是本领域普通技术人员所熟知的。
本文所用的药用盐,例如矿物质酸的盐如盐酸、溴化氢、磷酸盐、硫酸盐等;以及有机酸的盐,如乙酸盐、丙酸盐、丙二酸盐、苯甲酸盐等。对于药用赋形剂在《Remington药物学》(Mack Pub,Co.,N,J,1991)中有详细的讨论。
治疗组合物中的药用载体可以包含液体成分,如水、盐、甘油和乙醇。另外,辅助物质如湿润剂或乳化剂、pH缓冲物质等也可以包含在这种载体内。一般来说,治疗组合物制造成液体或悬液这种可注射的形式;在注射前适于溶解到液体中形成溶液或悬液的固体也可以制造。脂质体也包括在药用载体的范围内。
转移方法
组合物制造成制剂后可以直接注射给治疗对象,治疗对象可以是动物,但是特别适用于治疗人。
组合物的直接转移一般通过注射来完成,皮下、腹腔、静脉或肌肉注射,或者直接注射到组织的间质间隙。组合物也可以被注射到损伤部位。其他给药模式包括口服、肺吸入、栓剂、经真皮或经皮肤给药(见WO98/20734),利用针头以及基因泵或无针注射器给药。治疗剂量可以是单次剂量方案,也可以是多次剂量方案。
疫苗
本发明的疫苗可以是预防性的(即预防感染),也可以是治疗性的(即治疗感染后引起的疾病)。这种疫苗含有免疫抗原、免疫原、多肽、蛋白质或核酸,通常还包括“药用载体”,药用载体包括任何载体,只要其自身不能诱导产生对接受组合物的个体有害的抗体。适宜载体一般是大的慢代谢的大分子,如蛋白质、多糖、聚乳酸、聚乙醇酸、多聚氨基酸、氨基酸共聚物、脂质聚集物(如液滴或脂质体)以及灭活的病毒颗粒。这种载体是本领域技术人员所熟知的。
另外,这些载体还可以作为免疫刺激剂(“免疫佐剂”)。而且抗原或免疫原可以和细菌类毒素结合,如白喉、破伤风、霍乱、幽门螺旋菌等致病原来源的类毒素。
优选的能增强组合物效应的佐剂包括而不限于:(1)铝盐(明矾),如氢氧化铝、磷酸铝、硫酸铝等;(2)水包油乳化制剂(包含或不包含其他特异性的免疫刺激剂如胞壁酰肽(见下)或细菌细胞壁成分),如(a)MF59TM(WO 90/14837;《疫苗设计:亚单位和佐剂方法》第10章,Powell和Newman编,Plenum Press 1995),含有5%鲨烯、0.5%Tween 80和0.5%Span 85(尽管不是必须的,也可以选择添加不等量的MTP-PE(见下)),将这些物质用微粒液化器如Model 110Y微粒液化器(Microfluidics,Newton,MA)制造成亚微粒,(b)SAF,含有10%的鲨烯、0.4%Tween 80、5%pluronic封闭的聚合物L121、以及thr-MDP(见下),将这些物质液化成亚微粒乳液或剧烈搅拌成大颗粒乳液,以及(c)RiBiTM佐剂系统(RAS),(Ribi Immunochem,Hamilton,MT),含有2%的鲨烯、0.2%Tween 80和一种或多种细菌细胞壁成分,如单磷酸脂A(MPL)、海藻糖二真菌烷(TDM)和细胞壁骨架(CWS),优选MPL+CWS(DetoxTM);(3)皂甙佐剂,如StimulonTM(Cambridge Bioscience,Worcester,MA)或用其制成的颗粒如ISCOMs(免疫刺激复合物);(4)完全福氏佐剂(CFA)和不完全福氏佐剂(IFA);(5)细胞因子如白细胞介素(如IL-1、IL-2、IL-4、IL-5、IL-6、IL-7、IL-12等)、干扰素(如γ干扰素)、巨噬细胞集落刺激因子(M-CSF)、肿瘤坏死因子(TNF)等;以及(6)其他能增强组合物效应的免疫刺激因子。明矾和MF59TM是优选的。
如上所述,胞壁酰肽包括而不限于N-乙酰-胞壁酰-L-苏氨酰-D-异谷酰胺(thr-MDP)、N-乙酰-去甲胞壁酰-L-内氨酰-D-异谷酰胺(nor-MDP)、N-乙酰胞壁酰-L-内氨酰-D-异谷氨酰-L-丙氨酸-2-(1’-2’-棕榈酰-sn-甘油-3-羟基磷酰基氧基)-乙基酰胺(MTP-PE)等。
免疫原性组合物(即免疫抗原/免疫原/多肽/蛋白质/核酸、药用载体和佐剂)一般都含有稀释剂,如水、盐、甘油、乙醇等。另外,辅助物质如湿润剂或乳化剂、pH缓冲物质等也可以包含在这种载体中。
一般来说,免疫原性组合物制造成可注射的形式,如液体溶液或悬液;在注射前适于溶于液体介质中制造成溶液或悬液的固体形式也可以。另外,制剂也可以乳化或包裹到脂质体中以增强佐剂的效应,如上面所讨论的位于药用载体之下。
用作疫苗的免疫原性组合物含有免疫有效量的抗原性或免疫原性多肽,以及如果需要还可以添加上述任何其他组分。“免疫有效量”是指一次或多次给个体注射这个剂量后可以达到治疗或预防的效果。确定这个剂量的多少要根据患者健康状况和生理条件、所要处理的物种(即非人灵长类、人等)、个体免疫系统合成抗体的能力、期望得到的保护程度、疫苗的剂型、医生对医疗状况的评价以其他相关因素。剂量最好落在一个较宽的范围内,这个范围可以通过常规的试验来确定。
免疫原性组合物一般通过系统给药,如通过皮下、肌肉或真皮内/皮肤内注射(见WO98/20734)。适于其他给药模式的制剂包括口服制剂和肺吸入制剂、栓剂和真皮内给药。治疗剂量可以是单次剂量给药或多次剂量给药。疫苗也可以和其他免疫调节剂一起给药。
除了蛋白疫苗以外,也可以利用DNA进行免疫{见Robinson和Torres(1997)Seminars in Immunology 9:271-283;Donnelly等,(1997)Annu,Rev,Immunol,15:617-648;见本文下面的描述}。
基因转移载体
转移含本发明的治疗性编码序列的构建物所用的基因治疗载体可以通过局部或全身给药转移到哺乳动物体内使其表达。这些构建物可以利用病毒或非病毒载体在体内或体外表达。这种编码序列的表达可以用内源性的哺乳动物启动子或异源启动子来诱导。编码序列的体内表达可以是组成性的也可以是可调节的。
本发明包含能表达本发明所涉及的核酸序列的基因转移载体。基因转移载体优选病毒载体,更优选的是逆转录病毒、腺病毒、腺相关病毒(AAV)、疱疹病毒或甲病毒载体。病毒载体也可以是星状病毒、冠状病毒、正粘病毒、乳头多瘤空泡病毒、副粘液病毒、细小病毒、细小核糖核酸病毒、痘病毒或披膜病毒载体。见Jolly(1994)Cancer Gene Therapy 1:51-64;Kimura(1994)Human Gene Therapy 5:845-852;Connelly(1995)Human Gene Therapy 6:185-193;以及Kaplitt(1994)Nature Genetics6:148-153。
逆转录病毒是本领域所熟知的,我们认为任何逆转录病毒基因治疗载体都可用于本发明,其中包括B、C和D型逆转录病毒、嗜异性逆转录病毒(例如NZB-XL、NZB-X2和NZB9-1(见O’NEILL(1985)J Virol,53:160)、多嗜性逆转录病毒如MCF和MCF-MLV(见Kelly(1983)J Virol,45:291)、泡沫病毒和慢病毒。见《RNA肿瘤病毒》,第二版,Cold Spring Harbor Laboratory,1985。
逆转录病毒基因治疗载体的不同元件可以来源于不同的逆转录病毒,例如,逆转录病毒载体的LTRs可以来自鼠肉瘤病毒,tRNA结合位点可以来自劳氏肉瘤病毒,包装信号可以来自鼠白血病病毒,第二链合成起点可以来自禽类白血病病毒。
将这些重组逆转录病毒载体导入到适当的包装细胞系内可以制造出具有完全感染能力的逆转录病毒载体颗粒(见美国专利5,591,624)。通过将嵌合的整合酶掺入到逆转录病毒颗粒内可以构建出能以位点特异性的方式整合到宿主细胞DNA中的逆转录病毒载体(见WO96/37626)。重组病毒载体优选复制缺陷的重组病毒。
适于上述逆转录病毒载体的包装细胞是本领域所熟知的,也是易于制造的(见WO95/30763和WO92/05266),可用于制造病毒生产细胞(也称为载体细胞系或″VCLs″)以生产重组载体颗粒。优选的包装细胞系是来源于人的细胞(如HT1080细胞)或水貂的细胞系,这种细胞系在人血清中不被灭活。
用于构建逆转录病毒基因治疗载体的优选逆转录病毒包括禽类白血病病毒、牛白血病病毒、鼠白血病病毒、Mink-Cell Focus-Inducing Virus、鼠肉瘤病毒、网状内皮组织增生病病毒以及劳氏肉瘤病毒。特别优选的鼠白血病病毒包括4070A和1504A(Hartley和Rowe(1976)J Virol 19:19-25),Abelson(ATCC No,VR-999),Friend(ATCC No,VR-245),Graffi,Gross(ATCC Nol VR-590),Kirsten,Harvey肉瘤病毒和Rauscher(ATCC No,VR-998)以及莫洛尼鼠白血病病毒(ATCC No,VR-190)。这种病毒可从各个储藏中心或收集中心获得,如美国典型培养物收集中心(″ATCC″),Rockville,Maryland,或者利用常规的方法从已知的样品中分离。
本发明可用的逆转录病毒基因治疗载体的例子有下列文献中所描述的那些:专利申请GB2200651、EP0415731、EP0345242、EP0334301、WO89/02468、WO89/05349、WO89/09271、WO90/02806、WO90/07936、WO94/03622、WO93/25698、WO93/25234、WO93/11230、WO93/10218、WO91/02805、WO91/02825、WO95/07994、US 5,219,740、US 4,405,712、US 4,861,719、US4,980,289、US 4,777,127、US 5,591,624。也见于Vile(1993)Cancer Res 53:3860-3864;Vile(1993)Cancer Res 53:962-967;Ram(1993)Cancer Res 53(1993)83-88;Takamiya(1992)J Neurosci Res 33:493-503;Baba(1993)J Neurosurg 79:729-735;Mann(1983)Cell 33:153;Cane(1984)Proc Natl Acad Sci 81:6349;以及Miller(1990)Human GeneTherapy 1。
人腺病毒基因治疗载体也是本领域所熟知的,可用于本发明中。见Berkner(1988)Biotechniques 6:616和Rosenfeld(1991)Science 252:431,以及WO93/07283、WO93/06223和WO93/07282。可用于本发明的已知的腺病毒基因治疗载体的例子见上述参考文献以及下列专利文献中所描述的:WO94/12649、WO93/03769、WO93/19191、WO94/28938、WO95/11984、WO95/00655、WO95/27071、WO95/29993、WO95/34671、WO96/05320、WO94/08026、WO94/11506、WO93/06223、WO94/24299、WO95/14102、WO95/24297、WO95/02697、WO94/28152、WO94/24299、WO95/09241、WO95/25807、WO95/05835、WO94/18922和WO95/09654。另外,Curiel(1992)Hum,Gene Ther,3:147-154所描述的连接到灭活的腺病毒上的DNA也可以应用。本发明的基因转移载体还包括腺相关病毒(AAV)载体。本发明所用的优选载体是Srivastava,WO93/09239中所描述的AAV-2来源的载体。最好的AAV载体含有两个AAV末端反向重复序列,其中的天然D-序列中的某些核苷酸被替代,至少保留5个天然核苷酸到18个天然核苷酸,优选的是保留至少10到18个天然核苷酸,最优选的是至少保留10个天然核苷酸,D-序列上的其他核苷酸或者被删除或者被非天然核苷酸替代。AAV末端反向重复序列中的天然D-序列是一种每个AAV末端反向重复序列中都含有的20个连续核苷酸的序列(即每个末端都有一个D-序列),该序列不参与HP形成。替代的非天然核苷酸可以是任何一个和天然D序列相同位置上核苷酸不同的核苷酸。其他可用的AAV载体包括pWP-19和pWN-1,这两个载体都描述于Nahreini(1993)Gene 124:257-262。这种载体的另一个例子是psub201(见Samulski(1987)J.Virol,61:3096)。另外一种AAV载体是双D ITR载体。双D ITR载体的构建见美国专利5,478,745的描述。其他的载体见下列文献的描述:Carter的美国专利4,797,368和Muzyczka的美国专利5,139,941,Chartejee的美国专利5,474,935以及Kotin的WO94/288157。本发明可用的AAV载体的其他例子是SSV9AFABTKneo,其中含有AFP增强子和白蛋白启动子,这种载体在肝脏内高表达。其结构及构建方法见Su(1996)HumanGene therapy 7:463-470的描述。其他AAV基因治疗载体见US 5,354,678、US5,173,414、US 5,139,941和US 5,252,479的描述。
本发明的基因治疗载体还包括疱疹病毒。优选的例子是含胸腺激酶多肽编码序列的单纯疱疹病毒,如US 5,288,641和EP0176170(Roizman)所描述的。其他的单纯疱疹病毒载体包括HFEM/ICP6-LacZ,见WO95/04139(Wistar)的描述,pHSVlac,见Geller(1988)Science 241:1667-1669、WO90/09441和WO92/07945的描述,HSVUs3∷pgC-lacZ,见Fink(1992)Human Gene Therapy 3:11-19的描述,以及HSV 7134、2 RH 105和GAL4,见EP 0453242(Breakefield)的描述,还有ATCC所收藏的检索号为ATCC VR-977和ATCC VR-260的那些。
α病毒基因治疗载体也可用于本发明中。优选的α病毒载体是新培斯病毒载体。披膜病毒,塞姆利基森林病毒(ATCC VR-67;ATCC VR-1247),Middleberg病毒,(ATCC VR-370),罗斯河病毒(ATCC VR-373;ATCC VR-1246),委内瑞拉马脑炎病毒(ATCC VR923;ATCC VR-1250;ATCC VR-1249;ATCC VR-532),以及美国专利5,091,309、5,217,879和WO92/10578所描述的那些病毒。比较特殊的α病毒载体是US Serial No,08/405,627中所描述的那些病毒,出版日1995年3月15日,以及WO94/21792、WO92/10578、WO95/07994、US 5,091,309和US 5,217,879所描述的载体也可以使用。这种α病毒可以从各个储藏中心或收集中心获得,如ATCC,Rockville,Maryland,或者利用常规技术从已知样品中分离。优选的α病毒载体是具有减弱的细胞毒性的病毒(见USSN 08/679640)。
DNA载体系统如真核分层表达系统也可用于表达本发明的核酸。见WO95/07994对真核分层表达系统的详细描述。本发明优选的真核分层表达系统是来源于α病毒载体的,最优选的是来源于Sindbis病毒载体的。
适用于本发明的其他病毒载体包括来源于脊髓灰质炎病毒的载体,如ATCCVR-58以及Evans,Nature 339(1989)385和Sabin(1973)J Biol Standardization 1:115所描述的那些病毒;鼻病毒,如ATCC VR-1110和Arnold(1990)J Cell Biochem L401所描述的那些病毒;痘病毒如金丝雀痘病毒或痘苗病毒如ATCC VR-111和ATCCVR-2010以及Fisher-Hoch(1989)Proc Natl Acad Sci 86:317;Flexner(1989)Ann NYAcad Sci 569:86,Flexner(1990)Vaccine 8:17;US 4,603,112、US 4,769,330和WO89/01973所描述的那些病毒;SV40病毒,如ATCC VR-305以及Mulligan(1979)Nature 277:108和Madzak(1992)J Gen Virol 73:1 533所描述的那些病毒;流感病毒,如ATCC VR-797以及利用反向重组技术制造的重组流感病毒,这些技术描述于US5,166,057和Enami(1990)Proc Natl Acad Sci 87:3802-3805;Enami和Palese(1991)JVirol 65:2711-2713和Luytjes(1989)Cell 59:110,(也见于McMichael(1983)NEJ Med309:13和Yap(1978)Nature 273:238和Nature(1979)277:108);如EP-0386882和Buchschacher(1992)J.Virol,66:2731所描述的人免疫缺陷病毒;麻疹病毒,如ATCCVR-67和VR-1247以及EP-0440219所描述的那些病毒;奥拉病毒,如ATCCVR-368;毕巴汝病毒,如ATCC VR-600和ATCC VR-1240;犰狳病毒,如ATCCVR-922;屈曲病毒,如ATCC VR-64和ATCC VR-1241;摩根堡病毒,如ATCCVR-924;盖塔病毒,如ATCC VR-369和ATCC VR-1243;Kyzylagach病毒,如ATCC VR-927;马亚罗病毒,如ATCC VR-66;穆茨布病毒,如ATCC VR-580和ATCC VR-1244;恩杜姆病毒,如ATCC VR-371;Pixuna病毒,如ATCC VR-372和ATCC VR-1245;托纳特病毒,如ATCC VR-925;Triniti病毒,如ATCC VR-469;乌纳病毒,如ATCC VR-374;Whataroa病毒,如ATCC VR-926;Y-62-33病毒,如ATCC VR-375;O’Nyong病毒,东方脑炎病毒,如ATCC VR-65和ATCC VR-1242;西方脑炎病毒,如ATCC VR-70、ATCC VR-1251、ATCC VR-622和ATCCVR-1252;以及冠状病毒,如ATCC VR-740以及Hamre(1966)Proc Soc Exp Biol Med121:190所描述的那些病毒。
能转移到细胞内的本发明的组合物并不限于上面所提到的那些载体,其他的转移方法及培养介质也可以使用,例如核酸表达载体,连接或未连接灭活腺病毒的多聚阳离子浓缩DNA,见US Serial No,08/366,787,出版日期1994年12月30日,以及Curiel(1992)Hum Gene Ther 3:147-154的描述;连接DNA的配基,如Wu(1989)J Biol Chem 264:16985-16987所描述的;真核细胞转移载体细胞,如US Serial No,08/240,030,出版日期1994年5月9日,以及US Serial No,08/404,796所描述的;光聚合水凝胶材料的沉淀物,手持基因转移颗粒枪,见美国专利5,149,655的描述,电离辐射,如US5,206,152和WO92/11033的描述,核电荷中和或与细胞膜融合。其他的方法见Philip(1994)Mol Cell Biol 14:2411-2618和Woffendin(1994)Proc NatlAcad Sci 91:1581-1585的描述。
颗粒介导的基因转移也可以应用,见US Serial No,60/023,867。简言之,将序列插入到含常规控制序列的常规载体中进行高水平表达,然后与合成的基因转移分子进行共孵育,例如多聚DNA结合阳离子如多聚赖氨酸、鱼精蛋白和白蛋白,这些分子连接到细胞的靶配基如非唾液血清类粘蛋白(见Wu和Wu(1987)J.Biol,Chem,262:4429-4432)、胰岛素(见Hucked(1990)Biochem Pharmacol 40:253-263)、半乳糖(见Plank(1992)Bioconjugate Chem 3:533-539)、乳糖或运铁蛋白上。
裸DNA也可以使用。裸DNA的转导方法见WO90/11092和US 5,580,859的描述。利用可生物降解的乳胶珠可提高摄取的效率。DNA包被的乳胶珠经胞饮作用可以有效地转运到细胞内。乳胶珠经处理提高其疏水性后可以进一步改进这种方法,从而可以促进内体的破裂并将DNA释放到胞浆内。
如US 5,422,120、WO95/13796、WO94/23697、WO91/14445和EP-524,968所描述,脂质体也可以作为基因转移工具。如USSN,60/023,867所描述,在非病毒的基因转移中,编码多肽的核酸序列可以插入到含常规控制序列的常规载体中进行高水平表达,然后与合成的基因转移分子进行共孵育,例如多聚DNA结合阳离子如多聚赖氨酸、鱼精蛋白和白蛋白,这些分子连接到细胞的靶配基如非唾液血清类粘蛋白、胰岛素、半乳糖、乳糖或运铁蛋白上。其他的转移系统包括利用脂质体包裹DNA,DNA中所包含的基因位于各种组织特异性或全能启动子的控制之下。适宜的非病毒转移方法还包括机械转移系统,如Woffendin等,(1994)Proc.Natl.Acad.Sci.USA 91(24):11581-11585所描述的方法。
而且,编码序列及其表达产物还可以通过光聚合水凝胶材料的沉淀来转移。其他基因转移方法也可用于转移编码序列,例如,US 5,149,655所描述的利用手持基因颗粒枪;如US 5,206,152和WO92/11033所描述的利用电离辐射活化要转移的基因。脂质体和多聚阳离子基因转移载体见于下列文献的描述:US 5,422,120和4,762,915;WO95/13796;WO94/23697和WO91/14445;EP-0524968;以及Stryer,《生物化学》,236-240页(1975),W,H,Freeman,San Francisco;Szoka(1980)BiochemBiophys Acta 600:1;Bayer(1979)Biochem Biophys Acta 550:464;Rivnay(1987)MethEnzymol 149:119;Wang(1987)Proc Natl Acad Sci 84:7851;Plant(1989)Anal Biochem176:420。
多聚核苷酸组合物可以含有治疗有效量的基因治疗载体,如上面所述的那样。为了实现本发明,有效剂量应为每个治疗个体给予约0.01mg/kg到50mg/kg或0.05mg/kg到10mg/kg的DNA构建物。
基因转移方法
本发明的多聚核苷酸组合物制造好以后,可以(1)直接注射给受体;(2)在体外导入受体来源的细胞;(3)在体外进行重组蛋白表达。受体可以是哺乳动物或鸟类,也可以是人。
组合物的直接转移一般通过注射来完成,皮下、腹腔、静脉或肌肉注射,或者直接注射到组织的间质间隙。组合物也可以被注射到损伤部位。其他给药模式包括口服、肺吸入、栓剂、经真皮或经皮肤给药(见WO98/20734),利用针头以及基因泵或无针注射器给药。治疗剂量可以是单次剂量方案,也可以是多次剂量方案。在体外进行基因转导然后将转化的细胞再移植到受体内的方法是本领域所熟知的,见于WO93/14778的描述。能用于体外转导的细胞包括干细胞,特别是造血干细胞、淋巴细胞、巨噬细胞、树突状细胞或肿瘤细胞。
一般来说,体内和体外的基因转移采用如下方法:葡聚糖介导的转染、钙磷酸盐沉淀、多聚季胺介导的转染、原生质体融合、电穿孔、脂质体包裹以及将DNA直接微注射到细胞核内,这些方法都是本领域所熟知的。
多聚核苷酸和多肽药用组合物
除了上述的药用载体以外,下列试剂也可用于多聚核苷酸和/或多肽组合物:
A.多肽
多肽的例子包括而不限于:非唾液血清类粘蛋白(ASOR);运铁蛋白;唾液酸糖蛋白;抗体;抗体片段;铁蛋白;白细胞介素;干扰素;粒细胞-巨噬细胞集落刺激因子(GM-CSF);粒细胞集落刺激因子(G-CSF);巨噬细胞集落刺激因子(M-CSF);干细胞因子和促红细胞生成素。病毒抗原如包膜蛋白也可以使用。其他侵入性微生物来源的蛋白,如恶性疟原虫环孢子蛋白的17氨基酸肽,被称为RII。
B.激素、维生素等
其中包括:促黑激素、类固醇、雄激素、雌激素、甲状腺激素或维生素、叶酸。
C.多聚烷烯、多糖等
聚烷烯甘油也可以与多聚核苷酸/多肽组合。在个优选实施方式中,聚烷烯甘油是聚乙烯甘油。另外,也可以包括单糖、二糖或多糖。在一个优选实施方式中,多糖是二乙氨乙基葡聚糖。还可以是壳聚糖和聚(丙交酯-共-乙交酯)。
D.脂质和脂质体
本发明的多聚核苷酸/多肽在注射给受体前或导入到受体来源的细胞前也可以包裹在脂质内,或脂质体内。
脂质包裹一般用脂质体,脂质体能结合或包裹和保留核酸。浓缩多聚核苷酸与脂质的比例可以变化但是一般约为1∶1(mg DNA:mmol脂质),或者更多一点脂质。利用脂质体作为载体转移核酸的方法在下列文献中作了综述:Hug和Sleight(1991)Biochem.Biophys.Acta.1097:1-17;Straubinger(1983)Meth.Enzymol.101:512-527。
本发明所用的脂质体制剂包括阳离子制剂(带正电荷)、阴离子制剂(带负电荷)以及中性制剂。阳离子脂质体能介导质粒DNA(Felgner(1987)Proc.Natl.Acad.Sci.USA 84:7413-7416)、mRNA(Malone(1989)Proc.Natl.Acad.Sci.USA 86:6077-6081)以及纯化的转录因子(Debs(1990)J Biol,Chem,265:10189-10192)以功能形式向细胞内转移。
阳离子脂质体很容易得到。例如,N{1-2,3-二油酰氧基}丙基}-N,N,N-三乙基铵(DOTMA)脂质体的商品名是Lipofectin,是GIBCO BRL,Grand Island,NY的产品。(也见上述的Felgner)。其他商品化的脂质体包括转染体(DDAB/DOPE)和DOTAP/DOPE(Boerhinger)。另外,也可以利用易于获得的材料通过本领域熟知的方法制造阳离子脂质体。见Szoka(1978)Proc.Natl.Acad.Sci.USA 75:4194-4198;WO90/11092,其中描述了DOTAP(1,2-二(油酰氧基)-3-(三乙基氨基)丙烷)脂质体的制造方法。
阴离子脂质体和中性脂质体也很容易获得,如Avanti Polar Lipids(Birmingham,AL)的产品,或者利用易于获得的材料制造。这些材料包括磷脂酰胆碱、胆固醇、磷脂酰乙醇胺、二油酰磷脂酰胆碱(DOPC)、二油酰磷脂酰甘油(DOPG)、二油酰磷脂酰乙醇胺(DOPE)等。这些材料可以与DOTMA和DOTAP起始材料以适当的比例混合。利用这些材料制造脂质体的方法是本领域所熟知的。
脂质体包括多层囊泡(MLVs)、小的单层囊泡(SUVs)和大的单层囊泡(LUVs)。各种脂质体-核酸混合物都可以用本领域熟知的方法制造。见Straubinger(1983)Meth.Immunol.101:512-527;Szoka(1978)Proc.Natl.Acad.Sci.USA 75:4194-4198;Papahadjopoulos(1975)Biochim.Biophys.Acta 394:483;Wilson(1979)Cell 17:77;Deamer和Bangham(1976)Biochim.Biophys.Acta 443:629;Ostro(1977)Biochem.Biophys.Res.Commun.76:836;Fraley(1979)Proc.Natl.Acad.Sci.USA 76:3348;Enoch和Strittmatter(1979)Proc.Natl.Acad.Sci.USA 76:145;Fraley(1980)J Biol,Chem,(1980)255:10431;Szoka和Papahadjopoulos(1978)Proc.Natl.Acad.Sci.USA 75:145;以及Schaefer-Ridder(1982)Science 215:166。
E.脂蛋白
脂蛋白也可以和多聚核苷酸/多肽一起转移。可以利用的脂蛋白包括:乳糜微粒、HDL、IDL、LDL和VLDL。这些蛋白的突变体、片段或融合产物也可以使用。经修饰的天然脂蛋白也可以使用,如乙酰化的LDL。这些脂蛋白能使多聚核苷酸靶向性地导入到表达脂蛋白受体的细胞内。如果用脂蛋白与多聚核苷酸一起转移,那么最好在组合物中不包含其他的靶向性配基。
天然脂蛋白包括脂质和蛋白两部分。蛋白部分已知为载脂蛋白。到目前为止,共分离和鉴定出了载脂蛋白A、B、C、D和E。这几种蛋白中至少有两个包含几种亚型,分别用罗马数字表示,AI,AII,AIV;CI,CII,CIII。
一种脂蛋白可以包含多种载脂蛋白。例如,天然乳糜微粒包含载脂蛋白A、B、C以及E,经过一段时间的代谢后丢失掉A,又获得了C和E。VLDL含有载脂蛋白A、B、C和E,LDL含有载脂蛋白D;HDL含有载脂蛋白A、C和E。
载脂蛋白的氨基酸组成是已知的,例如在下列文献中有描述:Breslow(1985)Annu Rev.Biochem 54:699;Law(1986)Adv,Exp Med,Biol,151:162;Chen(1986)JBiol Chem 261:12918;Kane(1980)Proc Natl Acad Sci USA 77:2465;以及Utermann(1984)Hum Genet 65:232。
脂蛋白含有各种脂质,其中包括甘油三酯、胆固醇(游离胆固醇或胆固醇酯)和磷脂。天然脂蛋白内所包含的脂质组合是各种各样的。例如,乳糜微粒只要包含甘油三酯。天然脂蛋白内脂质成分的详细描述见Meth.Enzymol.128(1986)。脂质组合的选择要有助于载脂蛋白的受体结合活性,也要有助于提高其疏水活性以及和多聚核苷酸结合分子的结合。
天然脂蛋白可以从血清中分离,比如通过超速离心。这种方法描述于Meth.Enzymol.(如上所述);Pitas(1980)J Biochem,255:5454-5460以及Mahey(1979)J Clin,Invest,64:743-750。脂蛋白也可以在体外制造,或通过载脂蛋白基因在宿主细胞内表达的重组方法制造。见Atkinson(1986)Annu Rev Biophys Chem 15:403和Radding(1958)Biochim Biophys Acta 30:443。另外也可以从厂家购买,如Biomedical Techniologies,Inc.,Stoughton,Massachusetts,USA。关于脂蛋白的其他描述见Zuckermann等,PCT/US97/14465。
F.多聚阳离子试剂
多聚阳离子试剂可以包含在需转移的多聚核苷酸/多肽组合物中,其中可以含有,也可以不含有脂蛋白。
一般来说,多聚阳离子试剂在生理pH条件下带有的净电荷为正电荷,能中和核酸分子的电荷以促进其转移到指定部位。这些试剂在体内和体外都可以使用。多聚阳离子试剂可通过肌肉注射或皮下注射等方式用于将核酸转移到活体内。
下面是一些可用作多聚阳离子试剂的多肽:多聚赖氨酸、多聚精氨酸、多聚鸟氨酸以及鱼精蛋白。其他的例子包括组蛋白、已经蛋白、人血清白蛋白、DNA结合蛋白、非组蛋白的染色体蛋白、DNA病毒的包被蛋白如X174,转录因子也含有DNA结合区,因而也可以作为核酸浓缩试剂。简言之,转录因子如C/CEBP、c-iun、c-fos、AP-L、AP-2、AP-3、CPF、Prot-1、Sp-1、Oct-1、Oct-2、CREP以及TFIID都含有基本的DNA序列结合区。
有机多聚阳离子试剂包括:精胺、精醚和purtrescine。
根据上面所描述的多聚阳离子试剂的结构及生理特性可以构建出其他的多肽型多聚阳离子试剂或制造出合成的多聚阳离子试剂。
合成的多聚阳离子试剂包括二乙胺乙基葡聚糖、多聚季胺。Lipofectin和Lipofectamine是单体,与多聚核苷酸/多肽结合可以形成多聚阳离子复合物。
核酸杂交
“核酸杂交”是指两个核酸序列通过氢键彼此相连。通常的情况是一个序列固定在固相支持物上,另一个序列游离于溶液中。然后在适于氢键形成的条件下使两个序列彼此接触。影响氢键形成的因素包括:溶剂的类型和体积;反应温度;杂交时间;搅拌速度;封闭液相中的序列非特异地吸附到固相支持物上的试剂(Denhardt试剂或BLOTTO);序列的浓度;增加序列结合所使用的化合物(糖酐酯或聚乙烯甘油);以及杂交后洗涤条件的严谨性。见上述的Sambrook等,第2卷,第9章,9.47-9.57。
“严谨性”用于指杂交反应的条件,该条件适于两个不同序列之间极其相似的部分相结合。例如,温度和盐浓度的结合应选择在计算出的杂交Tm下约120℃到200℃。温度和盐浓度的确定一般通过预试验来确定,其中固定在膜上的基因组DNA与目的序列杂交,然后在不同严谨性的条件下洗涤。见Sambrook等,9.50页。
杂交试验是需要考虑的变量,例如,对于Southern印迹来说是(1)需杂交的DNA的复杂性和(2)探针与需检测的序列之间的同源性。试验中所需的片段总量可以10的数量级来变化,对于质粒和噬菌体消化产物来说,从0.1μg到10μg;对于含有单拷贝基因的高复杂性的真核基因组来说,从10-9g到10-8g。对于低复杂性的多聚核苷酸来说,较短的转膜、杂交和曝光时间,较少量的起始多聚核苷酸以及较低特异性的探针就可以。例如,检测单拷贝的酵母基因只需要1小时的曝光时间,1pg的起始酵母DNA,转膜2小时,杂交4-8小时,探针108cpm/μg。对于单拷贝的哺乳动物基因来说,保守的方法是以10μg DNA起始,转膜过夜,在10%硫酸葡聚糖存在的条件下杂交过夜,探针的量大于108cpm/μg,曝光时间为24小时。
几种因素可影响探针与目的片段之间DNA-DNA杂合子的解链温度(Tm),因此也会影响杂交和洗涤的条件。在许多情况下探针和目的片段并不是100%同源的。其他常遇到的变量包括杂交序列的长度和其G+C的总含量以及杂交缓冲液的离子强度和甲酰胺的含量。所有这些因素对Tm的影响可以用下面一个简单的等式近似地表示:
Tm=81+16.6(Log10Ci)+0.4{%(G+C)}-0.6(甲酰胺%)-600/n-1.5(不匹配%)
其中Ci代表盐浓度(单价离子),n代表杂合子碱基对的长度(根据Meinkoth和Wahl(1984)Anal,Biochem,138:267-284所描述的公式稍加修改)。
在设计杂交试验时,某些影响核酸杂交的条件可以适当改变。杂交和洗涤的温度以及洗涤的盐浓度是最容易改变的。如果杂交温度升高(即严谨性增加),非同源链之间杂交的可能性就会下降,同时背景也降低。如果放射性标记的探针与固定的片段不完全同源(在基因家族内和种间杂交试验时经常会出现),杂交温度应该降低,从而背景也会提高。洗涤温度也会以同样的方式影响杂交条带的强度和背景的高低。随着洗涤盐浓度的降低洗涤条件的严谨性增高。
在50%甲酰胺存在的条件下,探针与靶片段95%到100%同源时所需的杂交温度为42℃,90%到95%同源时所需的杂交温度为37℃,85%到90%同源时所需的杂交温度为32℃。如果同源性更低,那么就要降低甲酰胺的含量,同时根据上面的公式相应地调整温度。如果探针与靶片段之间的同源性是未知的,最简单的方法是以非严谨性的杂交条件和洗涤条件开始。如果经放射自显影后发现非特异性的条带和较高的背景,那么就用高严谨性的条件洗膜并从新曝光。如果曝光时间还无法使这种方法具有实用性,那么就需要采用几种严谨性的杂交和/或洗涤条件进行平行试验。
核酸探针分析
利用PCR、分支DNA探针分析或利用本发明的核酸探针进行印迹杂交可以确定是否存在cDNA或mRNA。如果一个探针可以和本发明的序列形成双链复合物,并且其稳定性足以被检测,那么就说这个探针可以和本发明的序列“杂交”。
核酸探针可以和本发明的衣原体核苷酸序列杂交(包括正义链和反义链)。虽然许多不同的核苷酸序列都可以编码同一个氨基酸序列,但是天然的衣原体序列是优选的,因为这种序列是细胞内实际存在的序列。MRNA代表了编码序列,因此探针应当与编码序列互补;单链cDNA与mRNA互补,因此cDNA探针应当与非编码序列互补。
探针序列并不需要与衣原体序列(或其互补链)完全一致-如果核酸探针能与靶核苷酸序列形成可检测的双链,那么序列的组成及长度发生某些改变可以提高分析的灵敏度。另外,核酸探针还可以包含能稳定所形成的双链的额外的核苷酸。例如,非互补的核苷酸序列可以连接到探针的5’端,探针的其余序列与衣原体序列互补。另外,非互补的碱基或较长的序列也可以分散在探针内,只要探针序列足以与衣原体序列互补并与之杂交从而形成可检测的双链。
探针的长度及序列组成要根据杂交的条件而定,如温度、盐浓度等。例如,如果用于诊断则要根据所分析序列的复杂性,一般选择至少含10-20个核苷酸的探针,优选15-25个,更好的是30个以上的核苷酸,尽管有时可能短一些。较短的探针一般需要较低的温度才能与模板形成稳定的杂合子。
探针可以通过合成的方法制造,如Matteucci等{J.Am.Chem.Soc.(1981)103:3185}或Urdea等,{Proc.Natl.Acad.Sci.USA(1983)80:7461}所述的三酯法,或者利用寡核苷酸自动合成仪合成。
根据参考文献可以选择探针的化学性质。对于某些应用来说,DNA或RNA就可以了。但是对于另外一些应用来说可以加入一些修饰,例如骨架修饰,如可通过硫代磷酸酯或甲基膦酸酯来增加体内的半衰期、改变RNA的亲和性、增加对核酶的耐受等{见Agrawal和Iyer(1995)Curr Opin,Biotechnol,6:12-19;Agrawal(1996)TIBTECH 14:376-387};类似物如肽核酸{见Corey(1997)TIBTECH 15:224-229;Buchardt等,(1993)TIBTECH 11:384-386}。
另外,多聚酶链式反应(PCR)是另外一种大家所熟知的检测小量靶核酸的方法。这种方法描述于Mullis等,{Meth.Enzymol.(1987)155:335-350};美国专利4,683,195和4,683,202。两个“引物”与靶核酸杂交后启动合成反应。引物种可以含有不与扩增靶序列(或其互补链)杂交的序列以增加双链的稳定性或为了添加限制性酶切位点。一般来说这种序列位于所要扩增的衣原体序列的两侧。
耐热的聚合酶以原始的靶核酸为模板从引物开始合成靶核酸序列的拷贝。靶核酸量的阈值是由聚合酶决定的,可以用不止一种常规方法检测,如Southern印迹。用Southern印迹方法时,标记的探针与衣原体序列(或其互补链)杂交。
MRNA或cDNA也可以用上述Sambrook等所描述的常规印迹技术检测。MRNA或利用聚合酶由mRNA合成的cDNA可用凝胶电泳分离和纯化。然后将凝胶上的核酸转到固相支持物上,如硝酸纤维素膜。固相支持物与标记的探针杂交,然后洗涤去掉未杂交的探针。再检测含标记探针的双链。探针一般用放射性基团标记。
附图的简要描述
图1到14显示的是实施例1到14的数据。图形为凝胶电泳图,泳道1位于图的左边。
对于Western印迹来说,每种蛋白检测两种样品。每对条带中的左侧条带用原免疫血清染色的一条膜,右侧条带用免疫血清染色的一条膜。在图1到5、图35B、图37B、图38B和图39的Western印迹图中,分子量标记分别为66、45、30、20.1和14.4kDa。在图6到16、图20B、23C、24D、27E、38A、40、41、42和43的Western印迹图中,分子量标记分别为172.6、111.4、79.6、61.3、49.0、36.4、24.7、19.2和13.1kDa。
图1到5的Western印迹图形中,条带1和2表示的抗GST融合对照抗原的对照血清,条带4和5表示的是抗His标记对照抗原的对照血清。
低分子量标记位于凝胶中的条带1中。
本发明的实施模式
表I列出了参考文献18所述的肺炎衣原体蛋白的名称、GenBank检索号及其滴度,以及与这些蛋白相应的本发明的沙眼衣原体蛋白的GenBank检索号和滴度,同时也列出了这些沙眼衣原体蛋白的序列号(SEQ IDs 1-262中奇数号代表氨基酸序列,偶数号代表核苷酸序列)。如参考文献18所描述的,相应的肺炎衣原体蛋白也可以用同样的方式表示。沙眼衣原体蛋白可用于诊断和免疫。这些特性单从序列上看是不明显的。
可用利用各种试验评价本发明的蛋白质的体内免疫原性。例如,重组表达这些蛋白后用免疫印迹技术筛选病人的血清。蛋白和病人血清如果发生阳性反应说明病人体内以前发生过针对该蛋白的免疫应答,即该蛋白是免疫原。这种方法也可用于鉴定蛋白的免疫优势表位。
通过常规方法可用重组蛋白制造抗体,如在小鼠体内。这样就可以直接确定蛋白质是否位于沙眼衣原体的细胞表面(即利用抗完整沙眼衣原体的抗体进行Western印迹)。标记的抗体(如用荧光标记进行FACS)可与完整的细菌共孵育,如果细菌表面存在标记物则可以确定蛋白的位置。FACS图说明了衣原体制造物在FACS分析中的分散情况,当重组抗原的抗体与衣原体细胞结合时会发生峰值漂移(空白区=对照样品;填充区=抗体反应样品),利用定量的Kolmogorov-Smirnov(K-S)方法进行统计学分析,利用FACS分析软件进行计算。
实施例1
在大肠杆菌中表达CT242(SEQ ID 57和SEQ ID 58)。重组产物以GST融合蛋白(图1A:条带4和5,色谱组分1和2,预计分子量为42.4kDa)和His标记融合蛋白(图1B:条带2-4,色谱组分1、2和3,预计分子量为16.4kDa)的形式纯化。
重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图1C:His标记融合蛋白:条带12和13;GST融合蛋白:条带20和21)。条带12显示的是用His标记CT242的原血清染色的膜条带,而条带13显示的是用His标记CT242的血清染色的膜条带。条带20显示的是用GST融合蛋白CT242的原血清染色的膜条带,而条带13显示的是用GST融合蛋白CT242的血清染色的膜条带。
这些试验说明CT242是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例2
在大肠杆菌中表达CT045(SEQ ID 71和SEQ ID 72)。重组产物以His标记融合蛋白(图2A:条带4-6,色谱组分1、2和3,预计分子量为55.8kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图2B,条带8和9)和FACS分析(图2C,K-S值为16.81)。
这些试验说明CT045是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例3
在大肠杆菌中表达CT381(SEQ ID 105和SEQ ID 106)。重组产物以GST融合蛋白(图3A:条带2和3,色谱组分1和2,预计分子量为52.7kDa)和His标记融合蛋白(图3A:条带7-9,色谱组分1、2和3,预计分子量为26.7kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Westem印迹分析(图3B:His标记融合蛋白:条带6和7;GST融合蛋白:条带16和17)和FACS分析(图3C:GST标记融合蛋白,K-S值为35.98;图3D:His标记融合蛋白,K-S值为32.54)。
这些试验说明CT381是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例4
在大肠杆菌中表达CT396(SEQ ID 107和SEQ ID 108)。重组产物以GST融合蛋白(图4A:条带6和7,色谱组分1和2,预计分子量为99.5kDa)和His标记融合蛋白(图4B:条带5-7,色谱组分1、2和3,预计分子量为73.5kDa)的形式纯化。重组His标记融合蛋白用于免疫小鼠,其血清用于Western印迹分析(图4C,条带14和15)和FACS分析(图4D:His标记融合蛋白,K-S值为34.50;图4E:GST标记融合蛋白,K-S值为32.76)。
这些试验说明CT396是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例5
在大肠杆菌中表达CT398(SEQ ID 111和SEQ ID 112)。重组产物以GST融合蛋白(图5A:条带8和9,色谱组分1和2,预计分子量为54.8kDa)和His标记融合蛋白(图5B:条带8-10,色谱组分1、2和3,预计分子量为28.8kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图5C:His标记融合蛋白:条带10和11;GST融合蛋白:条带18和19)和FACS分析(图5D:GST融合蛋白,K-S值为31.24;图5E:His标记融合蛋白,K-S值为26.10)。
这些试验说明CT398是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例6:在大肠杆菌中表达CT089(SEQ ID 61和SEQ ID 62)。重组产物以GST融合蛋白(图6C:条带2,色谱组分1,预计分子量为70.8kDa)和His标记融合蛋白(图6C:条带3、4和5,色谱组分1、2和3,预计分子量为44.8kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图6A:GST融合蛋白:条带14和15;His标记融合蛋白:条带16和17)和FACS分析(图6B:His标记融合蛋白,K-S值为26.59)。
这些试验说明CT089是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例7
在大肠杆菌中表达CT443(SEQ ID 125和SEQ ID 126)。重组产物以His标记融合蛋白的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图7A:条带10和11)和FACS分析(图7B:K-S值为21.28)。
这些试验说明CT443是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例8
在大肠杆菌中表达CT541(SEQ ID 149和SEQ ID 150)。重组产物以GST融合蛋白(图8C:条带2和3,色谱组分1和2,预计分子量为51.6kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图8A:条带6和7)和FACS分析(图8B:K-S值为9.94)。
这些试验说明CT541是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例9
在大肠杆菌中表达CT547(SEQ ID 151和SEQ ID 152)。重组产物以GST融合蛋白(图9D:条带4和5,色谱组分1和2,预计分子量为58.3kDa)和His标记融合蛋白的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图9A:His标记融合蛋白:条带20和21)和FACS分析(图9B:GST融合蛋白,K-S值为14.60和15.57;图9C:His标记融合蛋白,K-S值为28.21)。
这些试验说明CT547是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例10
在大肠杆菌中表达CT587(SEQ ID 189和SEQ ID 152)。重组产物以His标记融合蛋白(图10C:条带5、6和7,色谱组分1、2和3,预计分子量为47.5kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图10A:条带12和13)和FACS分析(图10B:His标记融合蛋白,K-S值为20.85)。
这些试验说明CT587是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例11
在大肠杆菌中表达CT266(SEQ ID 77和SEQ ID 78)。重组产物以His标记融合蛋白(图11C:条带11和12,色谱组分1和2,预计分子量为44.1kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图11A:条带4和5)和FACS分析(图11B:K-S值为21.29)。
这些试验说明CT266是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例12
在大肠杆菌中表达CT444(SEQ ID 127和SEQ ID 128)。重组产物以GST融合蛋白(图12B:条带2和3,色谱组分1和2,预计分子量为87.3kDa)和His标记融合蛋白(图12C:条带3和4,色谱组分2和3,预计分子量为9.0kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图12A:条带16和17)和FACS分析(图12D:GST融合蛋白,K-S值为14.98和15.57;图12E:His标记融合蛋白,K-S值为13.28)。
这些试验说明CT444是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例13
在大肠杆菌中表达CT559(SEQ ID 199和SEQ ID 200)。重组产物以His标记融合蛋白(图13C:条带2、3和4,色谱组分1、2和3,预计分子量为34.9kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图13A:条带6和7)和FACS分析(图13B:K-S值为23.21)。
这些试验说明CT559是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例14
在大肠杆菌中表达CT681(SEQ ID 155和SEQ ID 156)。重组产物以His标记融合蛋白(图14C:条带5和6,色谱组分1和2,预计分子量为41.8kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图14A:条带10和11)和FACS分析(图14B:K-S值为34.66)。
这些试验说明CT681是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例15
在大肠杆菌中表达CT713(SEQ ID 201和SEQ ID 202)。重组产物以His标记融合蛋白(图15B:条带4、5和6,色谱组分1、2和3,预计分子量为35.4kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图15A:条带12和13)和FACS分析(图15C:K-S值为25.82)。
这些试验说明CT713是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例16
在大肠杆菌中表达CT823(SEQ ID 229和SEQ ID 230)。重组产物以His标记融合蛋白(图16C:条带7、8和9,色谱组分1、2和3,预计分子量为53.9kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Wesrern印迹分析(图16A:条带14和15)和FACS分析(图16B:K-S值为26.62)。
这些试验说明CT823是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例17
在大肠杆菌中表达CT114(SEQ ID 243和SEQ ID 244)。重组产物以His标记融合蛋白(图17:条带6和7,色谱组分1和2,预计分子量为48.5kDa)的形式纯化。
实施例18
在大肠杆菌中表达CT198(SEQ ID 43和SEQ ID 44)。重组产物以His标记融合蛋白(图18A:条带6,色谱组分1,预计分子量为56.3kDa)的形式纯化。重组His标记融合蛋白用于免疫小鼠,其血清用于FACS分析(图18B)。
这些试验说明CT198只存在于部分EB异源群体中(如衣原体制造物一样)。如果存在则是一种暴露于细胞表面的免疫原性蛋白。这些特性单从序列上看是不明显的。
实施例19
在大肠杆菌中表达CT241(SEQ ID 55和SEQ ID 56)。重组产物以His标记融合蛋白(图19:条带4,色谱组分3,预计分子量为85.3kDa)的形式纯化。
实施例20
在大肠杆菌中表达CT350(SEQ ID 27和SEQ ID 28)。重组产物以His标记融合蛋白(图20A:条带2、3和4,色谱组分1、2和3,预计分子量为61.3kDa)和GST融合蛋白(图20A:条带7、8和9,色谱组分1、2和3,预计分子量为87.3kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图20B:His标记融合蛋白,条带4和5;GST融合蛋白:条带8和9)。
实施例21
在大肠杆菌中表达CT351(SEQ ID 25和SEQ ID 26)。重组产物以His标记融合蛋白(图21:条带2和3,色谱组分1和2,预计分子量为76.1kDa)的形式纯化。
实施例22
在大肠杆菌中表达CT391(SEQ ID 251和SEQ ID 252)。重组产物以His标记融合蛋白(图22:条带8和9,色谱组分1和2,预计分子量为32.6kDa)的形式纯化。
实施例23
在大肠杆菌中表达CT077(SEQ ID 65和SEQ ID 66)。重组产物以GST融合蛋白(图23:条带2和3,色谱组分1和2,预计分子量为59.7kDa)和His标记融合蛋白的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图23C:条带6和7)和FACS分析(图23B,His标记融合蛋白,K-S值为9.17)。
这些试验说明CT077是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例24
在大肠杆菌中表达CT181(SEQ ID 245和SFQ ID 246)。重组产物以GST融合蛋白(图24A:条带4,色谱组分1,预计分子量为50.1kDa)和His标记融合蛋白(图24B:条带2、3和4,色谱组分1、2和3,预计分子量为32.0kDa)的形式纯化。重组GST融合蛋白用于免疫小鼠,其血清用于Western印迹分析(图24D:条带4和5(箭头所指))和FACS分析(图24C:K-S值为7.62)。
这些试验说明CT181是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例25
在大肠杆菌中表达CT589(SEQ ID 185和SEQ ID 186)。重组产物以GST融合蛋白(图25A:条带4和5,色谱组分1和2,预计分子量为89.4kDa)和His标记融合蛋白(图25B:条带2和3,色谱组分1和2,预计分子量为63.4kDa)的形式纯化。重组GST融合蛋白用于免疫小鼠,其血清用于FACS分析(图25C)。
这些试验说明CT589只存在于部分EB异源群体中(如衣原体制造物一样)。如果存在则是一种暴露于细胞表面的免疫原性蛋白。这些特性单从序列上看是不明显的。
实施例26
在大肠杆菌中表达CT597(SEQ ID 179和SEQ ID 180)。重组产物以GST融合蛋白(图26A:条带5和6,色谱组分1和2,预计分子量为36.0kDa)和His标记融合蛋白(图26B:条带2、3和4,色谱组分1、2和3,预计分子量为10.3kDa)的形式纯化。
实施例27
在大肠杆菌中表达CT623(SEQ ID 163和SEQ ID 164)。重组产物以GST融合蛋白(图27A:条带3和4,色谱组分1和2,预计分子量为71.8kDa)和His标记融合蛋白(图27B:条带2、3和4,色谱组分1、2和3,预计分子量为45.8 kDa)的形式纯化。重组GST融合蛋白用于免疫小鼠,其血清用于Western印迹分析(图27E:GST标记融合蛋白,条带4(箭头所指);His标记融合蛋白,条带13(箭头所指))和FACS分析(图27C:GST标记融合蛋白:K-S值为15.89;图27D:His标记融合蛋白:K-S值为20.27)。
这些试验说明CT623是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例28
在大肠杆菌中表达CT700(SEQ ID 261和SEQ ID 262)。重组产物以GST融合蛋白(图28A:条带5、6和7,色谱组分1、2和3,预计分子量为73.7kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于FACS分析(图28B:K-S值为8.72)。
这些试验说明CT700是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例29
在大肠杆菌中表达CT761(SEQ ID 217和SEQ ID 218)。重组产物以GST融合蛋白(图29A:条带6和7,色谱组分1和2,预计分子量为63.9kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于FACS分析(图29B:K-S值为11.45)。
这些试验说明CT761是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例30
在大肠杆菌中表达CT415(SEQ ID 117和SEQ ID 118)。重组产物以GST融合蛋白(图30:条带3和4,色谱组分1和2,预计分子量为55.4kDa)的形式纯化。
实施例31
在大肠杆菌中表达CT454(SEQ ID 253和SEQ ID 254)。重组产物以His标记融合蛋白(图31:条带2和3,色谱组分1和2,预计分子量为56.2kDa)的形式纯化。
实施例32
在大肠杆菌中表达CT467(SEQ ID 129和SEQ ID 130)。重组产物以GST融合蛋白(图32:条带3和4,色谱组分1和2,预计分子量为65.6kDa)的形式纯化。
实施例33
在大肠杆菌中表达CT551(SEQ ID 257和SEQ ID 258)。重组产物以His标记融合蛋白(图33A:条带5、6和7,色谱组分1、2和3,预计分子量为34.1kDa)和GST融合蛋白(图33B:条带4和5,色谱组分1和2,预计分子量为60.1kDa)的形式纯化。
实施例34
在大肠杆菌中表达CT567(SEQ ID 195和SEQ ID 196)。重组产物以GST融合蛋白(图34A:条带8和9,色谱组分1和2,预计分子量为44.0kDa)和His标记融合蛋白(图34B:条带7和8,色谱组分1和2,预计分子量为18.3kDa)的形式纯化。
实施例35
在大肠杆菌中表达CT569(SEQ ID 193和SEQ ID 194)。重组产物以His标记融合蛋白(图35A:条带2、3和4,色谱组分1、2和3,预计分子量为11.2kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图35B:条带8和9,箭头所指)。
实施例36
在大肠杆菌中表达CT647(SEQ ID 169和SEQ ID 170)。重组产物以GST标记融合蛋白(图36:条带6和7,色谱组分1和2,预计分子量为45.7kDa)的形式纯化。
实施例37
在大肠杆菌中表达CT600(SEQ ID 173和SEQ ID 174)。重组产物以His融合蛋白(图37A:条带5、6和7,色谱组分1、2和3,预计分子量为19.5kDa)的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图37B:条带10和11,箭头所指)和FACS分析(图37C:K-S值为10.46)。
这些试验说明CT600是一种暴露于细胞表面的免疫原性蛋白,可作为免疫原。这些特性单从序列上看是不明显的。
实施例38
在大肠杆菌中表达CT279(SEQ ID 247和SEQ ID 248)。重组产物以GST标记融合蛋白和His融合蛋白的形式纯化。重组GST标记融合蛋白和His标记融合蛋白用于免疫小鼠,其血清用于Western印迹分析(图38A:His标记融合蛋白:条带5(箭头所指);图38B:GST标记融合蛋白:条带12和13(箭头所指)。
实施例39
在大肠杆菌中表达CT560(SEQ ID 259和SEQ ID 260)。重组产物以His标记融合蛋白的形式纯化。重组His标记融合蛋白用于免疫小鼠,其血清用于Western印迹分析(图39:条带6和7(箭头所指))。
实施例40
在大肠杆菌中表达CT389(SEQ ID 249和SEQ ID 250)。重组产物以GST标记融合蛋白的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图40:条带16和17(箭头所指))。
实施例41
在大肠杆菌中表达CT456(SEQ ID 255和SEQ ID 256)。重组产物以GST标记融合蛋白的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图41:条带2和3(箭头所指))。
实施例42
在大肠杆菌中表达CT622(SEQ ID 161和SEQ ID 162)。重组产物以His标记融合蛋白的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图42:条带9(箭头所指))。
实施例43
在大肠杆菌中表达CT759(SEQ ID 213和SEQ ID 214)。重组产物以His标记融合蛋白的形式纯化。重组蛋白用于免疫小鼠,其血清用于Western印迹分析(图43:条带8和9(箭头所指))。
实施例44
体外中和试验用于分析用本发明的不同重组蛋白免疫的小鼠的血清抑制沙眼衣原体感染培养物中真核细胞的能力,所用的细胞为LLCMK2(猕猴肾上皮细胞)。用SP(蔗糖-磷酸盐缓冲液)缓冲液制造4倍系列稀释的鼠多克隆血清。用完整EB的鼠抗血清作为阳性对照,以未免疫血清和SP缓冲液为阴性对照。从沙眼衣原体(血清型D)中纯化出EB,用SP缓冲液稀释,使其含有EB的浓度为3×105IFU/ml,将10μl这种悬液加到每个稀释度的血清中,终体积为100μl。在37℃使抗体与EB反应30分钟,然后从每个样品中取100pl反应混和液加到96孔板内用PBS洗涤的单层LLCMK2细胞上面,37℃、805×g离心1小时。
所有血清和对照都设双复孔。去除多余的接种物后细胞再用PBS漂洗一次,补充200μl添加20%FCS和1μg/ml放线菌酮的DMEM培养基,37℃孵育48小时。细胞用甲醇固定,细胞内衣原体感染产生的典型胞浆包涵体用荧光素标记的抗衣原体单克隆抗体(Meridian Diagnostics)染色。在稀释度及EB与宿主细胞比例合适的情况下,所观察到的包涵体数量被认为是等于能存活的衣原体数量,即这些衣原体能成功地感染宿主细胞(被命名为包涵体形成单位,IFU)。
荧光素标记的包涵体用40×的显微镜计数,每个孔内数四个视野。抗体反应产生的感染抑制以样品与SP(只有缓冲液)对照组相比其平均IFU降低的百分数来表示。根据平时的经验,如果一种血清能使感染性下降50%以上就被认为是“中和性的”,但是,考虑到整个筛选试验的复杂性(例如,宿主细胞或衣原体分离株的变化,在制造感染性接种物时环境条件的变化),能将EB感染性抑制到更低程度的血清也可以作为疫苗的候选者进行进一步的研究。图44A显示的是一个中和阳性血清的结果,而图44B显示的是一个中和阴性血清的结果。进行体外中和试验所用的血清来自于用上述实施例1-10、13-22、24-26以及29-37所提到的重组蛋白免疫的小鼠。结果见表II。这些结果说明CT045、CT242、CT381、CT396、CT398、CT467、CT547、CT587和CT681是特别优选的抑制试验衣原体感染的疫苗候选者。这些特性单从序列上看是不明显的。
在另一个试验中,利用交叉中和试验检测抗沙眼衣原体的血清抑制肺炎衣原体EB的能力。这种方法在上文中已有描述,但是从肺炎衣原体中纯化的EB是用SP稀释的,浓度为3×106IFU/ml,将10μl这种悬液加到每个稀释度的血清中,终体积为100μl。用CT242和CT467免疫所得到的血清可以于肺炎衣原体EB发生交叉中和反应。
本发明只是利用实施例进行描述,但是根据本发明的精神,在本发明的范围内作出某种变化也是值得赞许的。
参考文献(其内容已全部纳入本文作为参考)
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表II
Ref,18 | 肺炎衣原体检索号及注释 | 沙眼衣原体检索号及注释 | SEQ IDs |
Cp0010 | qi|4376729|gb|AAD18590.1|多形性的外膜蛋白G家族 | gi|3329346|gb|AAC68469.1|推测的外膜蛋白G | 1,2 |
Cp0014 | gi|4376729|gb|AAD18590.1|多形性的外膜蛋白G家族 | gi|3329346|gb|AAC68469.1|推测的外膜蛋白G | 3,4 |
cp0015 | gi|4376731|gb|AAD18591.1|多形性的外膜蛋白G/I家族 | gi|3329346|gb|AAC68469.1|推测的外膜蛋白G | 5,6 |
cp0016 | gi|4376731|gb|AAD18591.1|多形性的外膜蛋白G/I家族 | gi|3329350|gb|AAC68472.1|推测的外膜蛋白I | 7,8 |
cp0017 | gi|4376731|gb|AAD18591.1|多形性的外膜蛋白GII家族 | gi|3329346|gb|AAC68469.1|推测的外膜蛋白G | 9,10 |
cp0018 | gi|4376733|gb|AAD18593.1|多形性的外膜蛋白G家族 | gi|3328840|gb|AAC68009.1|推测的外膜蛋白A | 11,12 |
cp0019 | gi|4376731|gb|AAD18591.1|多形性的外膜蛋白G/I家族 | gi|3329346|gb|AAC68469.1|推测的外膜蛋白G | 13,14 |
cp0468 | gi|4376754|gb|AAD18611.1|多形性的外膜蛋白(C移码突变) | gi|13329344|gb|AAC68467.1|推测的外膜蛋白E | 15,16 |
cp6260 | gi|4376260|gb|AAD18163.1|多形性的外膜蛋白G家族 | gi|3329346|gb|AAC68469.1|推测的外膜蛋白G | 17,18 |
cp6262 | gi|4376262|gb|AAD18165.1|假设的蛋白 | gi|3328765|gb|AAC67940.1|假设的蛋白 | 19,20 |
cp6269 | gi|4376269|gb|AAD18171.1|假设的蛋白 | gi|3328825|gb|AAC67995.1|假设的蛋白 | 21,22 |
cp6270 | gi|4376270|gb|AAD18172.1|多形性的外膜蛋白G家族 | gi|3329350|gb|AAC68472.1|推测的外膜蛋白I | 23,24 |
cp6272 | gi|4376272|gb|AAD18173.1|预测的OMP{前导肽:外膜} | gi|33328772|gb|AAC67946.1|假设的蛋白 | 25,26 |
cp6273 | gi|4376273|gb|AAD18174.1|预测的OMP{前导肽} | gi|332871|gb|AAC67945.1|假设的蛋白 | 27,28 |
cp6296 | gi|4376296|gb|AAD18195.1|假设的蛋白 | gi|3328520|gb|AAC67712.1|核酮糖-P表位酶 | 29,30 |
cp6362 | gi|4376362|gb|AAD18254.1|YbbP家族假设的蛋白 | gi|3328401|gb|AAC67602.1|假设的蛋白 | 31,32 |
cp6372 | gi|4376372|gb|AAD18263.1|信号肽酶I | gi|3328410|gb|AAC67610.1|信号肽酶I | 33,34 |
cp6397 | gi|4376397|gb|AAD18286.1|CHLPS假设的蛋白 | gi|3328506|gb|AAC67700.1|CHLPS假设的蛋白 | 35,36 |
cp6402 | gi|4376402|gb|AAD18290.1|ACR家族 | gi|3328505|gb|AAC67699.1 ACR家族 | 37,38 |
cp6419 | gi|4376419|gb|AAD18305.1|CT149假设的蛋白 | gi|3328551|gb|AAC67740.1|可能的水解酶 | 39,40 |
cp6446 | gi|4376446|gb|AAD18330.1|假设的蛋白 | gi|3329261|gb|AAC68390.1|假设的蛋白 | 41,42 |
cp6466 | gi|4376466|gb|AAD18348.1|寡肽结合蛋白 | gi|3328604|gb|AAC67790.1|寡肽结合蛋白 | 43,44 |
cp6467 | gi|4376467|gb|AAD18349.1|寡肽结合蛋白 | gi|3328604|gb|AAC67790.1|寡肽结合蛋白 | 45,46 |
cp6468 | gi|4376468|gb|AAD18350.1|寡肽结合蛋白 | gi|3328539|gb|AAC67730.1|寡肽结合蛋白 | 47,48 |
cp6469 | gi|4376469|gb|AAD18351.1|寡肽结合蛋白 | gi|3328579|gb|AAC67766.1|寡肽结合蛋白permease | 49,50 |
cp6520 | gi|4376520|gb|AAD18398.1|多糖水解酶-透明质酸重复序列家族 | gi|3328526|gb|AAC67718.1|预测的多糖水解酶-透明质酸重复序列家族 | 51,52 |
cp6567 | gi|4376561|gb|AAD18441.1|包涵体膜蛋白C | gi|3328642|gb|AAC67825.1|包涵体膜蛋白C | 53,54 |
cp6576 | gi|4376576|gb|AAD18449.1|Omp85类似物 | gi|3328651|gb|AAC67834.1|Omp85类似物 | 55,56 |
cp6577 | gi|4376577|gb|AAD18450.1|(OmpH样外膜蛋白) | gi|3328652|gb|AAC67835.1|(OmpH样外膜蛋白) | 57,58 |
cp6601 | gi|4376601|gb|AAD18472.1|低钙反应性蛋白D | gi|3328486|gb|AAC67681.1|低钙反应性蛋白D | 59,60 |
cp6602 | gi|4376602|gb|AAD18473.1|低钙反应性蛋白E | gi|3328485|gb|AAC67680.1|低钙反应性蛋白E | 61,62 |
cp6607 | gi|4376607|gb|AAD18478.1|磷脂酶D超家族 | gi|3328479|gb|AAC67675.1|磷脂酶D超家族{前导(33)肽} | 63,64 |
cp6615 | gi|4376615|gb|AAD18485.1|YojL假设的蛋白 | gi|3328472|gb|AAC67668.1|假设的蛋白 | 65,66 |
cp6624 | gi|4376624|gb|AAD18493.1|溶质结合蛋白家族 | gi|3328461|gb|AAC67658.1|溶质结合蛋白家族 | 67,68 |
cp6639 | gi|4376639|gb|AAD18507.1|鞭毛分泌蛋白 | gi|3328453|gb|AAC67651.1|鞭毛分泌蛋白 | 69,70 |
cp6664 | gi|4376664|gb|AAD18529.1|亮氨酰氨肽酶A | gi|3328437|gb|AAC67636.1|亮氨酰氨肽酶A | 71,72 |
cp6672 | gi|4376672|gb|AAD18537.1|CBS域蛋白(红细胞溶解素类似物) | gi|3328667|gb|AAC67849.1|含CBS域的假设蛋白 | 73,74 |
cp6679 | gi|4376679|gb|AAD18543.1|CT253假设的蛋白 | gi|328664|gb|AAC67846.1|假设的蛋白 | 75,76 |
cp6696 | gi|4376696|gb|AAD18559.1|CT266假设的蛋白 | gi|3328678|gb|AAC67859.1假设的蛋白 | 77,78 |
cp6717 | gi|4376717|gb|AAD18579.1|磷脂酶D超家族 | gi|3328698|gb|AAC67877.1|磷脂酶D超家族 | 79,80 |
cp6727 | gi|4376727|gb|AAD18588.1|多形性的外膜蛋白G/I家族 | gi|3329346|gb|AAC68469.1|推测的外膜蛋白G | 81,82 |
cp6728 | gi|4376728|gb|AAD18589.1|多形性的外膜蛋白G家族 | gi|3329346|gb|AAC68469.1|推测的外膜蛋白G | 83,84 |
cp6729 | gi|4376729|gb|AAD18590.1|多形性的外膜蛋白G家族 | gi|329350|gb|AAC68472.1|推测的外膜蛋白1 | 85,86 |
cp6731 | gi|4376731|gb|AAD18591.1|多形性的外膜蛋白G/I家族 | gi|3329350|gb|AAC68472.1|推测的外膜蛋白I | 87,88 |
cp6733 | gi|4376733|gb|AAD18593.1|多形性的外膜蛋白G家族 | gi|3328840|gb|AAC68009.1|推测的外膜蛋白A | 89,90 |
cp6735 | gi|4376735|gb|AAD18594.1|多形性的外膜蛋白(截短的)A/I家族 | gi|3328840|gb|AAC68009.1|推测的外膜蛋白A | 91,92 |
cp6736 | gi|4376736|gb|AAD18595.1|多形性的外膜蛋白G家族 | gi|3329346|gb|AAC68469.1|推测的外膜蛋白G | 93,94 |
cp6737 | gi|4376737|gb|AAD18596.1|多形性的外膜蛋白H家族 | gi|3329347|gb|AAC68470.1|推测的外膜蛋白H | 95,96 |
cp6751 | gi|4376751|gb|AAD18608.1|多形性的外膜蛋白E家族 | gi|3329344|gb|AAC68467.1|推测的外膜蛋白E | 97,98 |
cp6752 | gi|4376752|gb|AAD18609.1|多形性的外膜蛋白E家族 | gi|3329344|gb|AAC68467.1|推测的外膜蛋白E | 99,100 |
cp6753 | gi|4376753|gb|AAD18610.1|多形性的外膜蛋白E/F家族 | gi|332934|gb|AAC68467.1|推测的外膜蛋白E | 101,102 |
cp6757 | gi|4376757|gb|AAD18613.1|假设的蛋白 | gi|3328701|gb|AAC67880.1|PP-loop超家族ATP酶 | 103,104 |
cp6767 | gi|4376767|gb|AAD18622.1|精氨酸胞质结合蛋白 | gi|3328806|gb|AAC67977.1|精氨酸结合蛋白 | 105,106 |
cp6790 | gi|4376790|gb|AAD18643.1|热休克蛋白-70 | gi|3328822|gb|AAC67993.1|HSP-70 | 107,108 |
cp6802 | gi|4376802|gb|AAD18654.1|CT427假设的蛋白 | gi|3328857|gb|AAC68024.1|假设的蛋白 | 109,110 |
cp6814 | gi|4376814|gb|AAD18665.1|CT398假设的蛋白 | gi|3328825|gb|AAC67995.1|假设的蛋白 | 111,112 |
cp6829 | gi|4376829|gb|AAD18679.1|多形性的膜蛋白A家族 | gi|3328840|gb|AAC68009.1|推测的外膜蛋白A | 113,114 |
cp6830 | gi|4376830|gb|AAD18680.1|多形性的膜蛋白B家族 | gi|3328841|gb|AAC68010.1|推测的外膜蛋白B | 115,116 |
cp6832 | gi|4376832|gb|AAD18681.1|溶质结合蛋白 | gi|3328844|gb|AAC68012.1|溶质结合蛋白 | 117,118 |
cp6834 | gi|4376834|gb|AAD18683.1|(金属转运蛋白) | gi|3328846|gb|AAC68014.2|(金属转运蛋白) | 119,120 |
cp6847 | gi|4376847|gb|AAD18695.1|尾巴特异性蛋白酶 | gi|3328872|gb|AAC68040.1|尾巴特异性蛋白酶 | 121,122 |
cp6848 | gi|4376848|gb|AAD18696.1|15kDa富含半胱氨酸的蛋白 | gi|3328873|gb|AAC68041.1|15kDa富含半胱氨酸的蛋白 | 123,124 |
cp6849 | gi|4376849|gb|AAD18697.1|60kDa富含半胱氨酸的OMP | gi|3328874|gb|AAC68042.1|60kDa富含半胱氨酸的OMP | 125,126 |
cp6850 | gi|4376850|gb|AAD18698.1|9kDa-富含半胱氨酸的脂蛋白 | gi|3328876|gb|AAC68043.1|9kDa-富含半胱氨酸的脂蛋白 | 127,128 |
cp6878 | gi|4376878|gb|AAD98723.1|2-组分传感器 | gi|3328901|gb|AAC68067.1|2-组分调节系统-传感器组氨酸激酶 | 129,130 |
cp6879 | gi|4376879|gb|AAD18724.1|CHLPS IncA类似物 | gi|3328451|gb|AAC67649.1|假设的蛋白 | 131,132 |
cp6884 | gi|4376884|gb AAD18729.1|CT471假设的蛋白 | gi|3328905|gb|AAC68071.1|假设的蛋白 | 133,134 |
cp6886 | gi|4376886|gb AAD18731.1|YidD家族 | gi|3328908|gb|AAC68073.1|假设的蛋白 | 135,136 |
cp6890 | gi|4376890|gb|AAD18734.1|CT476假设的蛋白 | gi|332891|gb|AAC68076.1|假设的蛋白 | 137,138 |
cp6892 | gi|4376892|gb|AAD18736.1|寡肽渗透酶 | gi|3328913|gb|AAC68078.1|寡肽渗透酶 | 139,140 |
cp6894 | gi|4376894|gb|AAD18738.1|寡肽结合脂蛋白 | gi|3328915|gb|AAC68080.1|寡肽结合脂蛋白 | 141,142 |
cp6900 | gi|4376900|gb|AAD18743.1|谷氨酰胺结合蛋白 | gi|3328922|gb|AAC68086.1|谷氨酰胺结合蛋白 | 143,144 |
cp6952 | gi|4376952|gb|AAD18792.1|载脂蛋白N-乙酰转移酶 | gi|3328972|gb|AAC68136.1|载脂蛋白N-乙酰转移酶 | 147,148 |
cp6960 | gi|4376960|gb|AAD18800.1|FKBP-型肽酰-脯氨酰-顺反式异构酶 | gi|3328979|gb|AAC68143.1|FKBP-型肽酰-脯氨酰-顺反式异构酶 | 149,150 |
cp6968 | gi|4376968|gb|AAD18807.1|CT547假设的蛋白 | gi|3328986|gb|AAC68149.1|假设的蛋白 | 151,152 |
cp6969 | gi|4376969|gb|AAD18808.1|CT548假设的蛋白 | gi|3328987|gb|AAC68150.1|假设的蛋白 | 153,154 |
cp6998 | gi|4376998|gb|AAD18834.1|主要外膜蛋白 | gi|3329133|gb|AAC68276.1|主要外膜蛋白 | 155,156 |
cp7005 | gi|4377005|gb|AAD18841.1|YopC/Gen分泌蛋白D | gi|3329125|gb|AAC68269.1|可能的Yop蛋白异位蛋白 | 157,158 |
cp7015 | gi|4377015|gb|AAD18851.1|FHA域;(与腺苷酸环化酶同源) | gi|3329115|gb|AAC68259.1|FHA域;(与腺苷酸环化酶同源) | 159,160 |
cp7033 | gi|4377033|gb|AAD18867.1|CHLPN 76kDa类似物_1(CT622) | gi|3329069|gb|AAC68226.1|CHLPN 76kDa类似物 | 161,162 |
cp7034 | gi|4377034|gb|AAD18868.1|CHLPN 76kDa类似物_2(CT623) | gi|6578109|gb|AAC68227.2|CHLPN 76kDa类似物 | 163,164 |
cp7035 | gi|4377035|gb|AAD18869.1|整合膜蛋白 | gi|3329071|gb|AAC68228.1|整合膜蛋白 | 165,166 |
cp7072 | gi|4377072|gb|AAD18902.1|CT648假设的蛋白 | gi|3329097|gb|AAC68825.1|假设的蛋白 | 167,168 |
cp7073 | gi|4377073|gb|AAD18903.1|CT647假设的蛋白 | gi|3329096|gb|AAC68824.1|假设的蛋白 | 169,170 |
cp7085 | gi|4377085|gb|AAD18914.1|CT605假设的蛋白 | gi|3329050|gb|AAC68208.1|假设的蛋白 | 171,172 |
cp7090 | gi|4377090|gb|AAD18919.1|肽聚糖相关脂蛋白 | gi|3329044|gb|AAC68202.1|肽聚糖相关脂蛋白 | 173,174 |
cp7091 | gi|4377091|gb|AAD18920.1|大分子转运蛋白 | gi|3329043|gb|AAC68201.1|大分子转运系统的组分 | 175,176 |
cp7092 | gi|4377092|gb|AAD18921.1|CT598假设的蛋白 | gi|3329042|gb|AAC68200.1|假设的蛋白 | 177,178 |
cp7093 | gi|4377093|gb|AAD18922.1|生物聚合物转运蛋白 | gi|3329041|gb|AAC68199.1|生物聚合物转运蛋白 | 179,180 |
cp7094 | gi|4377094|gb|AAD18923.1|大分子转运蛋白 | gi|3329040|gb|AAC68198.1|多糖转运蛋白 | 181,182 |
cp7101 | gi|4377101|gb|AAD18929.1|CT590假设的蛋白 | gi|3329033|gb|AAC68192.1|假设的蛋白 | 183,184 |
cp7102 | gi|4377102|gb|AAD18930.1|CT589假设的蛋白 | gi|3329032|gb|AAC68191.1|假设的蛋白 | 185,186 |
cp7106 | gi|4377106|gb|AAD18933.1|假设的蛋白 | gi|3328796|gb|AAC67968.1|假设的蛋白 | 187,188 |
cp7111 | gi|4377111|gb|AAD18938.1|烯醇化酶 | gi|3329030|gb|AAC68189.1|烯醇化酶 | 189,190 |
cp7127 | gi|4377127|gb|AAD18953.1|普通分泌蛋白D | gi|3329013|gb|AAC68174.1|普通分泌蛋白D | 191,192 |
cp7130 | gi|4377130|gb|AAD18956.1|预测的OMP{前导肽} | gi|3329010|gb|AAC68171.1|预测的OMP | 193,194 |
cp7132 | gi|4377132|gb|AAD18958.1|CT567假设的蛋白 | gi|3329008|gb|AAC68169.1|假设的蛋白 | 195,196 |
Cp7133 | gi|4377133|gb|AAD18959.1|CT566假设的蛋白 | gi|3329007|gb|AAC68168.1|假设的蛋白 | 197,198 |
Cp7140 | gi|4377140|gb|AAD18965.1|Yop异位J | gi|3329000|gb|AAC68161.1|Yop蛋白异位脂蛋白J | 199,200 |
Cp7170 | gi|4377170|gb|AAD18992.1|外膜蛋白B | gi|3329169|gb|AAC68308.1|外膜蛋白类似物 | 201,202 |
Cp7177 | gi|4377177|gb|AAD18998.1|鞭毛M-环蛋白 | gi|3329175|gb|AAC68314.1|鞭毛M-环蛋白 | 203,204 |
Cp7182 | gi|4377182|gb|AAD19003.1|CT724假设的蛋白 | gi|3329181|gb|AAC68319.1|假设的蛋白 | 205,206 |
Cp7184 | gi|4377184|gb|AAD19005.1|柱形蛋白 | gi|3329183|gb|AAC68321.1|柱形蛋白 | 207,208 |
Cp7193 | gi|4377193|gb|AAD19013.1|CT734假设的蛋白 | gi|3329192|gb|AAC68329.1|假设的蛋白 | 209,210 |
Cp7206 | gi|4377206|gb|AAD19025.1|CHLTR可能的磷蛋白 | gi|3329204|gb|AAC68339.1|CHLTR可能的磷蛋白 | 211,212 |
Cp7222 | gi|4377222|gb|AAD19040.1|溶菌酶(透明质酸酶重复序列家族) | gi|3329221|gb|AAC68354.1|溶菌酶(透明质酸酶重复序列家族) | 213,214 |
Cp7223 | gi|4377223|gb|lAAD19041.1|细胞分裂蛋白FtsW | gi|3329222|gb|AAC68355.1|细胞分裂蛋白FtsW | 215,216 |
Cp7224 | gi|4377224|gb|AAD19042.1|肽聚糖转移酶 | gi|3329223|gb|AAC68356.1|肽聚糖转移酶 | 217,218 |
Cp7225 | gi|4377225|gb|AAD19043.1|胞壁酸-丙氨酸连接酶&D-Ala-D-Ala连接酶 | gi|3329224|gb|AAC68357.1|UDP-N-乙酰胞壁酸丙氨酸连接酶 | 219,220 |
Cp7248 | gi|4377248|gb|AAD19064.1|硫氧还蛋白二硫化物异构酶 | gi|3329244|gb|AAC68375.1|硫氧还蛋白二硫化物异构酶 | 221,222 |
Cp7261 | gi|4377261|gb|AAD19076.1|CT788假设的蛋白{前导肽-胞质的} | gi|3329253|gb|AAC68383.1|{前导60肽-胞质的} | 223,224 |
Cp7280 | gi|4377280|gb|AAD19093.1|胰岛素酶家族/蛋白酶III | gi|3329273|gb|AAC68402.1|胰岛素酶家族/蛋白酶III | 225,226 |
Cp7287 | gi|4377287|gb|AAD19099.1|推测的外膜蛋白D家族 | gi|3329279|gb|AAC68408.1|推测的外膜蛋白D | 227,228 |
Cp7306 | gi|4377306|gb|AAD19116.1|DO丝氨酸蛋白酶 | gi|3329293|gb|AAC68420.1|DO丝氨酸蛋白酶 | 229,230 |
Cp7342 | gi|4377342|gb|AAD19149.1|ABC转运子渗透酶 | gi|3329327|gb|AAC68451.1|ABC转运子渗透酶-嘧啶生物合成蛋白 | 231,232 |
Cp7347 | gi|4377347|gb|AAD19153.1|CT858假设的蛋白 | gi|6578118|gb|AAC68456.2|预测的含IRBP和DHR域的蛋白酶 | 233,234 |
Cp7353 | gi|4377353|gb|AAD19159.1|CT863假设的蛋白 | gi|3329337|gb|AAC68461.1|假设的蛋白 | 235,236 |
Cp7367 | gi|4377367|gb|AAD19171.1|预测的OMP | gi|3328795|gb|AAC67967.1|假设的蛋白 | 237,238 |
Cp7408 | gi|4377408|gb|AAD19209.1|假设的蛋白 | gi|3328795|gb|AAC67967.1|假设的蛋白 | 239,240 |
Cp7409 | gi|4377409|gb|AAD19210.1|预测的外膜蛋白CT371 | gi|3328795|gb|AAC67967.1|假设的蛋白 | 241,242 |
gi14376411|gb| | gi|3328512|gb|AAC67705.1|假设的蛋白 | 243,244 | |
gi|4376508|gb| | gi|3328585|gb|AAC67772.1|假设的蛋白 | 245,246 | |
gi|4376710|gb| | gi|3328692|gb|AAC67872.1|NADH(泛醌)氧化还原酶,γ | 247,248 | |
gi|4376777|gb| | gi|3328815|gb|AAC67986.1|假设的蛋白 | 249,250 | |
gi|4376782|gb| | gi|3328817|gb|AAC67988.1|假设的蛋白 | 251,252 | |
gi|4376863|gb| | gi|3328887|gb|AAC68054.1|精氨酰tRNA转移酶 | 253,254 | |
gi|4376866|gb| | gi|3328889|gb|AAC68056.1|假设的蛋白 | 255,256 | |
gi|4376972|gb| | gi|3328991|gb|AAC68153.1|D-Ala-D-Ala羧肽酶 | 257,258 | |
gi|4377139|gb| | gi|3329001|gb|AAC68162.1|假设的蛋白 | 259,260 | |
gi|4377154|gb| | gi|3329154|gb|AAC68295.1|1假设的蛋白 | 261,262 |
表II
CT | 融合蛋白类型 | 中和50%时的滴度 | LLCMK2细胞培养物内EB感染在不同的血清稀释度下的中和百分率(%) | |||
1/40 | 1/160 | 1/640 | 1/2560 | |||
CT045 | His | 1∶160 | 32 | 50 | 18 | |
CT089 | His | 44 | 37 | 0 | ||
GST | 6 | 25 | 37 | |||
CT114 | His | 0 | 18 | |||
CT181 | GST | 19 | 0 | |||
CT198 | His | 19 | 0 | 13 | ||
CT241 | His | 5 | 42 | |||
CT242 | His | 1∶100 | 58 | 45 | 0 | |
GST | 46 | 24 | 40 | |||
CT350 | GST | 0 | 39 | |||
CT351 | His | 1 | 5 | |||
CT381 | His | 1∶450 | 67 | 56 | 48 | |
GST | 24 | 0 | 0 | |||
CT391 | His | 0 | 14 | |||
CT396 | His | 1∶300 | 55 | 62 | 35 | |
GST | 8 | 33 | 25 | |||
CT398 | His | 1∶640 | 57 | 45 | 50 | |
GST | 1∶>640 | 68 | 60 | 60 | ||
CT415 | GST | 21 | 21 | |||
CT427 | His | 25 | 13 | 13 | ||
CT443 | His | 25 | 25 | |||
CT454 | His | 16 | 4 | |||
CT467 | GST | 1∶1100 | 65 | 67 | 62 | 48 |
CT541 | GST | 10 | 24 | 13 | ||
CT547 | His | 1∶40 | 50 | 13 | 18 | |
GST | 0 | 0 | 18 | |||
CT551 | His | 5 | 11 | |||
CT559 | His | 20 | 23 | |||
CT567 | GST | 0 | 26 | |||
CT569 | His | 0 | 5 | |||
CT587 | His | 1∶1200 | 51 | 61 | 56 | 42 |
CT589 | His | 37 | 21 | |||
GST | 0 | 33 | ||||
CT597 | GST | 0 | 4 | |||
CT600 | His | 0 | 11 | |||
CT647 | GST | 15 | 0 | |||
CT681 | His | 1∶160 | 95 | 53 | ||
CT713 | His | 10 | 10 | |||
CT761 | GST | 0 | 16 | |||
CT823 | His | 5 | 23 | |||
NN-GST | 0 | 0 | 0 | |||
NN-His | 0 | 0 | 0 |
序列表
SEQ ID 1:
MQTSFHKFFLSMILAYSCCSLSGGGYAAEIMIPQGIYDGETLTVSFPYTVIGDPSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLTF
ENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATTNNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAIDAKSLTVQ
GISKLCVFQENTAQADGGACQVVTSFSAMANEAPIAFIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFDGNVARVGGGIYSYGNVAFL
NNGKTLFLNNVASPVYIAAEQPTNGQASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSSNVAAGKGGAIYAKKLSVANCGPVQFLGNIAN
DGGAIYLGESGELSLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKITTLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTG
DIVFANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGSTLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPPAQDSHP
AIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKIDVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTANNGPYTLKATWTKTGYNP
GPERVASLVPNSLWGSILDIRSAHSAIQASVDGRSYCRGLWVSGVSNFFYHDRDALGQGYRYISGGYSLGANSYFGSSMFGLAFTEVFGRSKDYVVCRSN
HHACIGSVYLSTKQALCGSYLFGDAFIRASYGFGNQHMKTSYTFAEESDVRWDNNCLVGEIGVGLPIVITPSKLYLNELRPFVQAEFSYADHESFTEEGD
QARAFRSGHLMNLSVPVGVKFDRCSSTHPNKYSFMGAYICDAYRTISGTQTTLLSHQETWTTDAFHLARHGVIVRGSMYASLTSNIEVYGHGRYEYRDTS
RGYGLSAGSKVRF
SEQ ID 2:
ATGCAAACGTCTTTCCATAAGTTCTTTCTTTCAATGATTCTAGCTTATTCTTGCTGCTCTTTAAGTGGGGGGGGGTATGCAGCAGAAATCATGATTCCTC
AAGGAATTTACGATGGGGAGACGTTAACTGTATCATTTCCCTATACTGTTATAGGAGATCCGAGTGGGACTACTGTTTTTTCTGCAGGAGAGTTAACGTT
AAAAAATCTTGACAATTCTATTGCAGCTTTGCCTTTAAGTTGTTTTGGGAACTTATTAGGGAGTTTTACTGTTTTAGGGAGAGGACACTCGTTGACTTTC
GAGAACATACGGACTTCTACAAATGGAGCTGCACTAAGTGACAGCGCTAATAGCGGGTTATTTACTATTGAGGGTTTTAAAGAATTATCTTTTTCCAATT
GCAACTCATTACTTGCCGTACTGCCTGCTGCAACGACTAATAATGGTAGCCAGACTCCGACGACAACATCTACACCGTCTAATGGTACTATTTATTCTAA
AACAGATCTTTTGTTACTCAATAATGAGAAGTTCTCATTCTATAGTAATTTAGTCTCTGGAGATGGGGGAGCTATAGATGCTAAGAGCTTAACGGTTCAA
GGAATTAGCAAGCTTTGTGTCTTCCAAGAAAATACTGCTCAAGCTGATGGGGGAGCTTGTCAAGTAGTCACCAGTTTCTCTGCTATGGCTAACGAGGCTC
CTATTGCCTTTATAGCGAATGTTGCAGGAGTAAGAGGGGGAGGGATTGCTGCTGTTCAGGATGGGCAGCAGGGAGTGTCATCATCTACTTCAACAGAAGA
TCCAGTAGTAAGTTTTTCCAGAAATACTGCGGTAGAGTTTGATGGGAACGTAGCCCGAGTAGGAGGAGGGATTTACTCCTACGGGAACGTTGCTTTCCTG
AATAATGGAAAAACCTTGTTTCTCAACAATGTTGCTTCTCCTGTTTACATTGCTGCTGAGCAACCAACAAATGGACAGGCTTCTAATACGAGTGATAATT
ACGGAGATGGAGGAGCTATCTTCTGTAAGAATGGTGCGCAAGCAGCAGGATCCAATAACTCTGGATCAGTTTCCTTTGATGGAGAGGGAGTAGTTTTCTT
TAGTAGCAATGTAGCTGCTGGGAAAGGGGGAGCTATTTATGCCAAAAAGCTCTCGGTTGCTAACTGTGGCCCTGTACAATTCTTAGGGAATATCGCTAAT
GATGGTGGAGCGATTTATTTAGGAGAATCTGGAGAGCTCAGTTTATCTGCTGATTATGGAGATATTATTTTCGATGGGAATCTTAAAAGAACAGCCAAAG
AGAATGCTGCCGATGTTAATGGCGTAACTGTGTCCTCACAAGCCATTTCGATGGGATCGGGAGGGAAAATAACGACATTAAGAGCTAAAGCAGGGCATCA
GATTCTCTTTAATGATCCCATCGAGATGGCAAACGGAAATAACCAGCCAGCGCAGTCTTCCGAACCTCTAAAAATTAACGATGGTGAAGGATACACAGGG
GATATTGTTTTTGCTAATGGAAACAGTACTTTGTACCAAAATGTTACGATAGAGCAAGGAAGGATTGTTCTTCGTGAAAAGGCAAAATTATCAGTGAATT
CTCTAAGTCAGACAGGTGGGAGTCTGTATATGGAAGCTGGGAGTACATTGGATTTTGTAACTCCACAACCACCACAACAGCCTCCTGCCGCTAATCAGTT
GATCACGCTTTCCAATCTGCATTTGTCTCTTTCTTCTTTGTTAGCAAACAATGCAGTTACGAATCCTCCTACCAATCCTCCAGCGCAAGATTCTCATCCT
GCAATCATTGGTAGCACAACTGCTGGTTCTGTTACAATTAGTGGGCCTATCTTTTTTGAGGATTTGGATGATACAGCTTATGATAGGTATGATTGGCTAG
GTTCTAATCAAAAAATCGATGTCCTGAAATTACAGTTAGGGACTCAGCCCTCAGCTAATGCCCCATCAGATTTGACTCTAGGGAATGAGATGCCTAAGTA
TGGCTATCAAGGAAGCTGGAAGCTTGCGTGGGATCCTAATACAGCAAATAATGGTCCTTATACTCTGAAAGCTACATGGACTAAAACTGGGTATAATCCT
GGGCCTGAGCGAGTAGCTTCTTTGGTTCCAAATAGTTTATGGGGATCCATTTTAGATATACGATCTGCGCATTCAGCAATTCAAGCAAGTGTGGATGGGC
GCTCTTATTGTCGAGGATTATGGGTTTCTGGAGTTTCGAATTTCTTCTATCATGACCGCGATGCTTTAGGTCAGGGATATCGGTATATTAGTGGGGGTTA
TTCCTTAGGAGCAAACTCCTACTTTGGATCATCGATGTTTGGTCTAGCATTTACCGAAGTATTTGGTAGATCTAAAGATTATGTAGTGTGTCGTTCCAAT
CATCATGCTTGCATAGGATCCGTTTATCTATCTACCAAACAAGCTTTATGTGGATCCTATTTGTTCGGAGATGCGTTTATCCGTGCTAGCTACGGGTTTG
GGAACCAGCATATGAAAACCTCATACACATTTGCAGAGGAGAGCGATGTTCGTTGGGATAATAACTGTCTGGTTGGAGAGATTGGAGTGGGATTACCGAT
TGTGATTACTCCATCTAAGCTCTATTTGAATGAGTTGCGTCCTTTCGTGCAAGCTGAGTTTTCTTATGCCGATCATGAATCTTTTACAGAGGAAGGCGAT
CAAGCTCGGGCATTCAGGAGTGGACATCTCATGAATCTATCAGTTCCTGTTGGAGTAAAATTTGATCGATGTTCTAGTACACACCCTAATAAATATAGCT
TTATGGGGGCTTATATCTGTGATGCTTATCGCACCATCTCTGGGACTCAGACAACACTCCTATCCCATCAAGAGACATGGACAACAGATGCCTTTCATTT
GGCAAGACATGGAGTCATAGTTAGAGGGTCTATGTATGCTTCTCTAACAAGCAATATAGAAGTATATGGCCATGGAAGATATGAGTATCGAGATACTTCT
CGAGGTTATGGTTTGAGTGCAGGAAGTAAAGTCCGGTTCTAA
SEQ ID 3:
MQTSFHKFFLSMILAYSCCSLSGGGYAAEIMIPQGIYDGETLTVSFPYTVIGDPSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLTF
ENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATTNNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAIDAKSLTVQ
GISKLCVFQENTAQADGGACQVVTSFSAMANEAPIAFIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFDGNVARVGGGIYSYGNVAFL
NNGKTLFLNNVASPVYIAAEQPTNGQASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSSNVAAGKGGAIYAKKLSVANCGPVQFLGNIAN
DGGAIYLGESGELSLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKITTLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTG
DIVFANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGSTLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPPAQDSHP
AIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKIDVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTANNGPYTLKATWTKTGYNP
GPERVASLVPNSLWGSILDIRSAHSAIQASVDGRSYCRGLWVSGVSNFFYHDRDALGQGYRYISGGTSLGANSYFGSSMFGLAFTEVFGRSKDYVVCRSN
HHACIGSVYLSTKQALCGSYLFGDAFIRASYGFGNQHMKTSYTFAEESDVRWDNNCLVGEIGVGLPIVITPSKLYLNELRPFVQAEFSYADHESFTEEGD
QARAFRSGHLMNLSVPVGVKFDRCSSTHPNKYSFMGAYICDAYRTISGTQTTLLSHQETWTTDAFHLARHGVIVRGSMYASLTSNIEVYGHGRYEYRDTS
RGYGLSAGSKVRF
SEQ ID 4:
ATGCAAACGTCTTTCCATAAGTTCTTTCTTTCAATGATTCTAGCTTATTCTTGCTGCTCTTTAAGTGGGGGGGGGTATGCAGCAGAAATCATGATTCCTC
AAGGAATTTACGATGGGGAGACGTTAACTGTATCATTTCCCTATACTGTTATAGGAGATCCGAGTGGGACTACTGTTTTTTCTGCAGGAGAGTTAACGTT
AAAAAATCTTGACAATTCTATTGCAGCTTTGCCTTTAAGTTGTTTTGGGAACTTATTAGGGAGTTTTACTGTTTTAGGGAGAGGACACTCGTTGACTTTC
GAGAACATACGGACTTCTACAAATGGAGCTGCACTAAGTGACAGCGCTAATAGCGGGTTATTTACTATTGAGGGTTTTAAAGAATTATCTTTTTCCAATT
GCAACTCATTACTTGCCGTACTGCCTGCTGCAACGACTAATAATGGTAGCCAGACTCCGACGACAACATCTACACCGTCTAATGGTACTATTTATTCTAA
AACAGATCTTTTGTTACTCAATAATGAGAAGTTCTCATTCTATAGTAATTTAGTCTCTGGAGATGGGGGAGCTATAGATGCTAAGAGCTTAACGGTTCAA
GGAATTAGCAAGCTTTGTGTCTTCCAAGAAAATACTGCTCAAGCTGATGGGGGAGCTTGTCAAGTAGTCACCAGTTTCTCTGCTATGGCTAACGAGGCTC
CTATTGCCTTTATAGCGAATGTTGCAGGAGTAAGAGGGGGAGGGATTGCTGCTGTTCAGGATGGGCAGCAGGGAGTGTCATCATCTACTTCAACAGAAGA
TCCAGTAGTAAGTTTTTCCAGAAATACTGCGGTAGAGTTTGATGGGAACGTAGCCCGAGTAGGAGGAGGGATTTACTCCTACGGGAACGTTGCTTTCCTG
AATAATGGAAAAACCTTGTTTCTCAACAATGTTGCTTCTCCTGTTTACATTGCTGCTGAGCAACCAACAAATGGACAGGCTTCTAATACGAGTGATAATT
ACGGAGATGGAGGAGCTATCTTCTGTAAGAATGGTGCGCAAGCAGCAGGATCCAATAACTCTGGATCAGTTTCCTTTGATGGAGAGGGAGTAGTTTTCTT
TAGTAGCAATGTAGCTGCTGGGAAAGGGGGAGCTATTTATGCCAAAAAGCTCTCGGTTGCTAACTGTGGCCCTGTACAATTCTTAGGGAATATCGCTAAT
GATGGTGGAGCGATTTATTTAGGAGAATCTGGAGAGCTCAGTTTATCTGCTGATTATGGAGATATTATTTTCGATGGGAATCTTAAAAGAACAGCCAAAG
AGAATGCTGCCGATGTTAATGGCGTAACTGTGTCCTCACAAGCCATTTCGATGGGATCGGGAGGGAAAATAACGACATTAAGAGCTAAAGCAGGGCATCA
GATTCTCTTTAATGATCCCATCGAGATGGCAAACGGAAATAACCAGCCAGCGCAGTCTTCCGAACCTCTAAAAATTAACGATGGTGAAGGATACACAGGG
GATATTGTTTTTGCTAATGGAAACAGTACTTTGTACCAAAATGTTACGATAGAGCAAGGAAGGATTGTTCTTCGTGAAAAGGCAAAATTATCAGTGAATT
CTCTAAGTCAGACAGGTGGGAGTCTGTATATGGAAGCTGGGAGTACATTGGATTTTGTAACTCCACAACCACCACAACAGCCTCCTGCCGCTAATCAGTT
GATCACGCTTTCCAATCTGCATTTGTCTCTTTCTTCTTTGTTAGCAAACAATGCAGTTACGAATCCTCCTACCAATCCTCCAGCGCAAGATTCTCATCCT
GCAATCATTGGTAGCACAACTGCTGGTTCTGTTACAATTAGTGGGCCTATCTTTTTTGAGGATTTGGATGATACAGCTTATGATAGGTATGATTGGCTAG
GTTCTAATCAAAAAATCGATGTCCTGAAATTACAGTTAGGGACTCAGCCCTCAGCTAATGCCCCATCAGATTTGACTCTAGGGAATGAGATGCCTAAGTA
TGGCTATCAAGGAAGCTGGAAGCTTGCGTGGGATCCTAATACAGCAAATAATGGTCCTTATACTCTGAAAGCTACATGGACTAAAACTGGGTATAATCCT
GGGCCTGAGCGAGTAGCTTCTTTGGTTCCAAATAGTTTATGGGGATCCATTTTAGATATACGATCTGCGCATTCAGCAATTCAAGCAAGTGTGGATGGGC
GCTCTTATTGTCGAGGATTATGGGTTTCTGGAGTTTCGAATTTCTTCTATCATGACCGCGATGCTTTAGGTCAGGGATATCGGTATATTAGTGGGGGTTA
TTCCTTAGGAGCAAACTCCTACTTTGGATCATCGATGTTTGGTCTAGCATTTACCGAAGTATTTGGTAGATCTAAAGATTATGTAGTGTGTCGTTCCAAT
CATCATGCTTGCATAGGATCCGTTTATCTATCTACCAAACAAGCTTTATGTGGATCCTATTTGTTCGGAGATGCGTTTATCCGTGCTAGCTACGGGTTTG
GGAACCAGCATATGAAAACCTCATACACATTTGCAGAGGAGAGCGATGTTCGTTGGGATAATAACTGTCTGGTTGGAGAGATTGGAGTGGGATTACCGAT
TGTGATTACTCCATCTAAGCTCTATTTGAATGAGTTGCGTCCTTTCGTGCAAGCTGAGTTTTCTTATGCCGATCATGAATCTTTTACAGAGGAAGGCGAT
CAAGCTCGGGCATTCAGGAGTGGACATCTCATGAATCTATCAGTTCCTGTTGGAGTAAAATTTGATCGATGTTCTAGTACACACCCTAATAAATATAGCT
TTATGGGGGCTTATATCTGTGATGCTTATCGCACCATCTCTGGGACTCAGACAACACTCCTATCCCATCAAGAGACATGGACAACAGATGCCTTTCATTT
GGCAAGACATGGAGTCATAGTTAGAGGGTCTATGTATGCTTCTCTAACAAGCAATATAGAAGTATATGGCCATGGAAGATATGAGTATCGAGATACTTCT
CGAGGTTATGGTTTGAGTGCAGGAAGTAAAGTCCGGTTCTAA
SEQ ID 5:
MQTSFHKFFLSMILAYSCCSLSGGGYAAEIMIPQGIYDGETLTVSFPYTVIGDPSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLTF
ENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATTNNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAIDAKSLTVQ
GISKLCVFQENTAQADGGACQVVTSFSAMANEAPIAFIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFDGNVARVGGGIYSYGNVAFL
NNGKTLFLNNVASPVYIAAEQPTNGQASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSSNVAAGKGGAIYAKKLSVANCGPVQFLGNIAN
DGGAIYLGESGELSLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKITTLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTG
DIVFANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGSTLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPPAQDSHP
AIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKIDVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTANNGPYTLKATWTKTGYNP
GPERVASLVPNSLWGSILDIRSAHSAIQASVDGRSYCRGLWVSGVSNFFYHDRDALGQGYRYISGGYSLGANSYFGSSMFGLAFTEVFGRSKDYVVCRSN
HHACIGSVYLSTKQALCGSYLFGDAFIRASYGFGNQHMKTSYTEAEESDVRWDNNCLVGEIGVGLPIVITPSKLYLNELRPFVQAEFSYADHESFTEEGD
QARAFRSGHLMNLSVPVGVKFDRCSSTHPNKYSFMGAYICDAYRTISGTQTTLLSHQETWTTDAFHLARHGVIVRGSMYASLTSNIEVYGHGRYEYRDTS
RGYGLSAGSKVRF
SEQ ID 6:
ATGCAAACGTCTTTCCATAAGTTCTTTCTTTCAATGATTCTAGCTTATTCTTGCTGCTCTTTAAGTGGGGGGGGGTATGCAGCAGAAATCATGATTCCTC
AAGGAATTTACGATGGGGAGACGTTAACTGTATCATTTCCCTATACTGTTATAGGAGATCCGAGTGGGACTACTGTTTTTTCTGCAGGAGAGTTAACGTT
AAAAAATCTTGACAATTCTATTGCAGCTTTGCCTTTAAGTTGTTTTGGGAACTTATTAGGGAGTTTTACTGTTTTAGGGAGAGGACACTCGTTGACTTTC
GAGAACATACGGACTTCTACAAATGGAGCTGCACTAAGTGACAGCGCTAATAGCGGGTTATTTACTATTGAGGGTTTTAAAGAATTATCTTTTTCCAATT
GCAACTCATTACTTGCCGTACTGCCTGCTGCAACGACTAATAATGGTAGCCAGACTCCGACGACAACATCTACACCGTCTAATGGTACTATTTATTCTAA
AACAGATCTTTTGTTACTCAATAATGAGAAGTTCTCATTCTATAGTAATTTAGTCTCTGGAGATGGGGGAGCTATAGATGCTAAGAGCTTAACGGTTCAA
GGAATTAGCAAGCTTTGTGTCTTCCAAGAAAATACTGCTCAAGCTGATGGGGGAGCTTGTCAAGTAGTCACCAGTTTCTCTGCTATGGCTAACGAGGCTC
CTATTGCCTTTATAGCGAATGTTGCAGGAGTAAGAGGGGGAGGGATTGCTGCTGTTCAGGATGGGCAGCAGGGAGTGTCATCATCTACTTCAACAGAAGA
TCCAGTAGTAAGTTTTTCCAGAAATACTGCGGTAGAGTTTGATGGGAACGTAGCCCGAGTAGGAGGAGGGATTTACTCCTACGGGAACGTTGCTTTCCTG
AATAATGGAAAAACCTTGTTTCTCAACAATGTTGCTTCTCCTGTTTACATTGCTGCTGAGCAACCAACAAATGGACAGGCTTCTAATACGAGTGATAATT
ACGGAGATGGAGGAGCTATCTTCTGTAAGAATGGTGCGCAAGCAGCAGGATCCAATAACTCTGGATCAGTTTCCTTTGATGGAGAGGGAGTAGTTTTCTT
TAGTAGCAATGTAGCTGCTGGGAAAGGGGGAGCTATTTATGCCAAAAAGCTCTCGGTTGCTAACTGTGGCCCTGTACAATTCTTAGGGAATATCGCTAAT
GATGGTGGAGCGATTTATTTAGGAGAATCTGGAGAGCTCAGTTTATCTGCTGATTATGGAGATATTATTTTCGATGGGAATCTTAAAAGAACAGCCAAAG
AGAATGCTGCCGATGTTAATGGCGTAACTGTGTCCTCACAAGCCATTTCGATGGGATCGGGAGGGAAAATAACGACATTAAGAGCTAAAGCAGGGCATCA
GATTCTCTTTAATGATCCCATCGAGATGGCAAACGGAAATAACCAGCCAGCGCAGTCTTCCGAACCTCTAAAAATTAACGATGGTGAAGGATACACAGGG
GATATTGTTTTTGCTAATGGAAACAGTACTTTGTACCAAAATGTTACGATAGAGCAAGGAAGGATTGTTCTTCGTGAAAAGGCAAAATTATCAGTGAATT
CTCTAAGTCAGACAGGTGGGAGTCTGTATATGGAAGCTGGGAGTACATTGGATTTTGTAACTCCACAACCACCACAACAGCCTCCTGCCGCTAATCAGTT
GATCACGCTTTCCAATCTGCATTTGTCTCTTTCTTCTTTGTTAGCAAACAATGCAGTTACGAATCCTCCTACCAATCCTCCAGCGCAAGATTCTCATCCT
GCAATCATTGGTAGCACAACTGCTGGTTCTGTTACAATTAGTGGGCCTATCTTTTTTGAGGATTTGGATGATACAGCTTATGATAGGTATGATTGGCTAG
GTTCTAATCAAAAAATCGATGTCCTGAAATTACAGTTAGGGACTCAGCCCTCAGCTAATGCCCCATCAGATTTGACTCTAGGGAATGAGATGCCTAAGTA
TGGCTATCAAGGAAGCTGGAAGCTTGCGTGGGATCCTAATACAGCAAATAATGGTCCTTATACTCTGAAAGCTACATGGACTAAAACTGGGTATAATCCT
GGGCCTGAGCGAGTAGCTTCTTTGGTTCCAAATAGTTTATGGGGATCCATTTTAGATATACGATCTGCGCATTCAGCAATTCAAGCAAGTGTGGATGGGC
GCTCTTATTGTCGAGGATTATGGGTTTCTGGAGTTTCGAATTTCTTCTATCATGACCGCGATGCTTTAGGTCAGGGATATCGGTATATTAGTGGGGGTTA
TTCCTTAGGAGCAAACTCCTACTTTGGATCATCGATGTTTGGTCTAGCATTTACCGAAGTATTTGGTAGATCTAAAGATTATGTAGTGTGTCGTTCCAAT
CATCATGCTTGCATAGGATCCGTTTATCTATCTACCAAACAAGCTTTATGTGGATCCTATTTGTTCGGAGATGCGTTTATCCGTGCTAGCTACGGGTTTG
GGAACCAGCATATGAAAACCTCATACACATTTGCAGAGGAGAGCGATGTTCGTTGGGATAATAACTGTCTGGTTGGAGAGATTGGAGTGGGATTACCGAT
TGTGATTACTCCATCTAAGCTCTATTTGAATGAGTTGCGTCCTTTCGTGCAAGCTGAGTTTTCTTATGCCGATCATGAATCTTTTACAGAGGAAGGCGAT
CAAGCTCGGGCATTCAGGAGTGGACATCTCATGAATCTATCAGTTCCTGTTGGAGTAAAATTTGATCGATGTTCTAGTACACACCCTAATAAATATAGCT
TTATGGGGGCTTATATCTGTGATGCTTATCGCACCATCTCTGGGACTCAGACAACACTCCTATCCCATCAAGAGACATGGACAACAGATGCCTTTCATTT
GGCAAGACATGGAGTCATAGTTAGAGGGTCTATGTATGCTTCTCTAACAAGCAATATAGAAGTATATGGCCATGGAAGATATGAGTATCGAGATACTTCT
CGAGGTTATGGTTTGAGTGCAGGAAGTAAAGTCCGGTTCTAA
SEQ ID 7:
MRPDHMNFCCLCAAILSSTAVLFGQDPLGETALLTKNPNHVVCTFFEDCTMESLFPALCAHASQDDPLYVLGNSYCWFVSKLHITDPKEALFKEKGDLSI
QNFRFLSFTDCSSKESSPSIIHQKNGQLSLRNNGSMSFCRNHAEGSGGAISADAFSLQHNYLFTAFEENSSKGNGGAIQAQTFSLSRNVSPISFARNRAD
LNGGAICCSNLICSGNVNPLFFTGNSATNGGAICCISDLNTSEKGSLSLACNQETLFASNSAKEKGGAIYAKHMVLRYNGPVSFINNSAKIGGAIAIQSG
GSLSILAGEGSVLFQNNSQRTSDQGLVRNAIYLEKDAILSSLEARNGDILFFDPIVQESSSKESPLPSSLQASVTSPTPATASPLVIQTSANRSVIFSSE
RLSEEEKTPDNLTSQLQQPIELKSGRLVLKDRAVLSAPSLSQDPQALLIMEAGTSLKTSSDLKLATLSIPLHSLDTEKSVTIHAPNLSIQKIFLSNSGDE
NFYENVELLSKEQNNIPLLTLSKEQSHLHLPDGNLSSHFGYQGDWTFSWKDSDEGHSLIANWTPKNYVPHPERQSTLVANTLWNTYSDMQAVQSMINTIA
HGGAYLFGTWGSAVSNLFYAHDSSGKPIDNWHHRSLGYLFGISTHSLDDHSFCLAAGQLLGKSSDSFITSTETTSYIATVQAQLATPLMKISAQACYNES
IHELKTKYRSFSKEGFGSWHSVAVSGEVCASIPIVSNGSGLFSSFSIFSKLQGFSGTQDGFEESSGEIRSFSASSFRNISLPMGITFEKKSQKTRNYYYF
LGAYIQDLKRDVESGPVVLLKNAVSWDAPMANLDSRAYMFRLTNQRALHRLQTLLNVSYVLRGQSHSYSLDLGTTYRF
SEQ ID 8:
ATGCGACCTGATCATATGAACTTCTGTTGTCTATGTGCTGCTATTTTGTCATCCACAGCGGTCCTCTTTGGCCAGGATCCCTTAGGTGAAACCGCCCTCC
TCACTAAAAATCCTAATCATGTCGTCTGTACATTTTTTGAGGACTGTACCATGGAGAGCCTCTTTCCTGCTCTTTGTGCTCATGCATCACAAGATGATCC
TTTGTATGTACTTGGAAATTCCTACTGTTGGTTCGTATCTAAACTCCATATCACGGACCCCAAAGAGGCTCTTTTTAAAGAAAAAGGAGATCTTTCCATT
CAAAATTTTCGCTTCCTTTCCTTCACAGATTGCTCTTCCAAGGAAAGCTCTCCTTCTATTATTCATCAAAAGAATGGTCAGTTATCCTTGCGCAATAATG
GTAGCATGAGTTTCTGTCGAAATCATGCTGAAGGCTCTGGAGGAGCCATCTCTGCGGATGCCTTTTCTCTACAACACAACTATCTTTTCACAGCTTTTGA
AGAGAATTCTTCTAAAGGAAATGGCGGAGCCATTCAGGCTCAAACCTTCTCTTTATCTAGAAATGTGTCGCCTATTTCTTTCGCCCGTAATCGTGCGGAT
TTAAATGGCGGCGCTATTTGCTGTAGTAATCTTATTTGTTCAGGGAATGTAAACCCTCTCTTTTTCACTGGAAACTCCGCCACGAATGGAGGCGCTATTT
GTTGTATCAGCGATCTAAACACCTCAGAAAAAGGCTCTCTCTCTCTTGCTTGTAACCAAGAAACGCTATTTGCAAGCAATTCTGCTAAAGAAAAAGGCGG
GGCTATTTATGCCAAGCACATGGTATTGCGTTATAACGGTCCTGTTTCCTTCATTAACAACAGCGCTAAAATAGGTGGAGCTATCGCCATCCAGTCCGGA
GGGAGTCTCTCTATCCTTGCAGGTGAAGGATCTGTTCTGTTCCAGAATAACTCCCAACGCACCTCCGACCAAGGTCTAGTAAGAAACGCCATCTACTTAG
AGAAAGATGCGATTCTTTCTTCCTTAGAAGCTCGCAACGGAGATATTCTTTTCTTTGATCCTATTGTACAAGAAAGTAGCAGCAAAGAATCGCCTCTTCC
CTCCTCTTTGCAAGCCAGCGTGACTTCTCCCACCCCAGCCACCGCATCTCCTTTAGTTATTCAGACAAGTGCAAACCGTTCAGTGATTTTCTCGAGCGAA
CGTCTTTCTGAAGAAGAAAAAACTCCTGATAACCTCACTTCCCAACTACAGCAGCCTATCGAACTGAAATCCGGACGCTTAGTTTTAAAAGATCGCGCTG
TCCTTTCCGCGCCTTCTCTCTCTCAGGATCCTCAAGCTCTCCTCATTATGGAAGCGGGAACTTCTTTAAAAACTTCCTCTGATTTGAAGTTAGCTACGCT
AAGTATTCCCCTTCATTCCTTAGATACTGAAAAAAGCGTAACTATCCACGCCCCTAACCTTTCTATCCAAAAGATCTTCCTCTCTAATTCTGGAGATGAG
AATTTTTATGAAAATGTAGAGCTTCTCAGTAAAGAGCAAAACAATATTCCTCTCCTTACTCTCTCTAAAGAGCAATCTCATTTACATCTTCCTGATGGGA
ACCTCTCTTCTCACTTTGGATATCAAGGAGATTGGACTTTTTCTTGGAAAGATTCTGATGAAGGGCATTCTCTGATTGCTAATTGGACGCCTAAAAACTA
TGTGCCTCATCCAGAACGTCAATCTACACTCGTTGCGAACACTCTTTGGAACACCTATTCCGATATGCAAGCTGTGCAGTCGATGATTAATACAATAGCG
CACGGAGGAGCCTATCTATTTGGAACGTGGGGATCTGCTGTTTCTAATTTATTCTATGCTCACGACAGCTCTGGGAAACCTATCGATAATTGGCATCATA
GAAGCCTTGGCTACCTATTCGGTATCAGTACTCACAGTTTAGATGACCATTCTTTCTGCTTGGCTGCAGGACAATTACTCGGGAAATCGTCCGATTCCTT
TATTACGTCTACAGAAACGACCTCCTATATAGCTACTGTACAAGCGCAACTCGCTACCCCTCTAATGAAAATCTCTGCACAGGCATGCTATAATGAAAGT
ATCCATGAGCTAAAAACAAAATATCGCTCCTTCTCTAAAGAAGGATTCGGATCCTGGCATAGCGTTGCAGTATCCGGAGAAGTGTGCGCATCGATTCCTA
TTGTATCCAATGGTTCCGGACTGTTCAGCTCCTTCTCTATTTTCTCTAAACTGCAAGGATTTTCAGGAACACAGGACGGTTTTGAGGAGAGTTCGGGAGA
GATTCGGTCCTTTTCTGCCAGCTCTTTCAGAAATATTTCACTTCCTATGGGAATAACATTTGAAAAAAAATCCCAAAAAACACGAAACTACTATTACTTT
CTGGGAGCCTACATCCAAGACCTAAAACGTGATGTGGAATCGGGACCTGTAGTGTTACTCAAAAATGCCGTCTCCTGGGATGCTCCTATGGCGAACTTGG
ATTCGCGAGCCTACATGTTCAGGCTTACGAATCAAAGAGCTCTGCATAGACTTCAGACGCTGTTAAATGTGTCTTACGTACTGCGCGGGCAAAGCCATAG
TTACTCCCTGGATCTGGGGACCACTTACAGGTTCTAG
SEQ ID 9:
MQTSFHKFFLSMILAYSCCSLSGGGYAAEIMIPQGIYDGETLTVSFPYTVIGDPSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLTF
ENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATTNNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAIDAKSLTVQ
GISKLCVFQENTAQADGGACQVVTSFSAMANEAPIAFIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFDGNVARVGGGIYSYGNVAFL
NNGKTLFLNNVASPVYIAAEQPTNGQASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSSNVAAGKGGAIYAKKLSVANCGPVQFLGNIAN
DGGAIYLGESGELSLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKITTLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTG
DIVFANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGSTLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPPAQDSHP
AIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKIDVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTANNGPYTLKATWTKTGYNP
GPERVASLVPNSLWGSILDIRSAHSAIQASVDGRSYCRGLWVSGVSNFFYHDRDALGQGYRYISGGYSLGANSYFGSSMFGLAFTEVFGRSKDYVVCRSN
HHACIGSVYLSTKQALCGSYLFGDAFIRASYGFGNQHMKTSYTFAEESDVRWDNNCLVGEIGVGLPIVITPSKLYLNELRPFVQAEFSYADHESFTEEGD
QARAFRSGHLMNLSVPVGVKFDRCSSTHPNKYSFMGAYICDAYRTISGTQTTLLSHQETWTTDAFHLARHGVIVRGSMYASLTSNIEVYGHGRYEYRDTS
RGYGLSAGSKVRF
SEQ ID 10:
ATGCAAACGTCTTTCCATAAGTTCTTTCTTTCAATGATTCTAGCTTATTCTTGCTGCTCTTTAAGTGGGGGGGGGTATGCAGCAGAAATCATGATTCCTC
AAGGAATTTACGATGGGGAGACGTTAACTGTATCATTTCCCTATACTGTTATAGGAGATCCGAGTGGGACTACTGTTTTTTCTGCAGGAGAGTTAACGTT
AAAAAATCTTGACAATTCTATTGCAGCTTTGCCTTTAAGTTGTTTTGGGAACTTATTAGGGAGTTTTACTGTTTTAGGGAGAGGACACTCGTTGACTTTC
GAGAACATACGGACTTCTACAAATGGAGCTGCACTAAGTGACAGCGCTAATAGCGGGTTATTTACTATTGAGGGTTTTAAAGAATTATCTTTTTCCAATT
GCAACTCATTACTTGCCGTACTGCCTGCTGCAACGACTAATAATGGTAGCCAGACTCCGACGACAACATCTACACCGTCTAATGGTACTATTTATTCTAA
AACAGATCTTTTGTTACTCAATAATGAGAAGTTCTCATTCTATAGTAATTTAGTCTCTGGAGATGGGGGAGCTATAGATGCTAAGAGCTTAACGGTTCAA
GGAATTAGCAAGCTTTGTGTCTTCCAAGAAAATACTGCTCAAGCTGATGGGGGAGCTTGTCAAGTAGTCACCAGTTTCTCTGCTATGGCTAACGAGGCTC
CTATTGCCTTTATAGCGAATGTTGCAGGAGTAAGAGGGGGAGGGATTGCTGCTGTTCAGGATGGGCAGCAGGGAGTGTCATCATCTACTTCAACAGAAGA
TCCAGTAGTAAGTTTTTCCAGAAATACTGCGGTAGAGTTTGATGGGAACGTAGCCCGAGTAGGAGGAGGGATTTACTCCTACGGGAACGTTGCTTTCCTG
AATAATGGAAAAACCTTGTTTCTCAACAATGTTGCTTCTCCTGTTTACATTGCTGCTGAGCAACCAACAAATGGACAGGCTTCTAATACGAGTGATAATT
ACGGAGATGGAGGAGCTATCTTCTGTAAGAATGGTGCGCAAGCAGCAGGATCCAATAACTCTGGATCAGTTTCCTTTGATGGAGAGGGAGTAGTTTTCTT
TAGTAGCAATGTAGCTGCTGGGAAAGGGGGAGCTATTTATGCCAAAAAGCTCTCGGTTGCTAACTGTGGCCCTGTACAATTCTTAGGGAATATCGCTAAT
GATGGTGGAGCGATTTATTTAGGAGAATCTGGAGAGCTCAGTTTATCTGCTGATTATGGAGATATTATTTTCGATGGGAATCTTAAAAGAACAGCCAAAG
AGAATGCTGCCGATGTTAATGGCGTAACTGTGTCCTCACAAGCCATTTCGATGGGATCGGGAGGGAAAATAACGACATTAAGAGCTAAAGCAGGGCATCA
GATTCTCTTTAATGATCCCATCGAGATGGCAAACGGAAATAACCAGCCAGCGCAGTCTTCCGAACCTCTAAAAATTAACGATGGTGAAGGATACACAGGG
GATATTGTTTTTGCTAATGGAAACAGTACTTTGTACCAAAATGTTACGATAGAGCAAGGAAGGATTGTTCTTCGTGAAAAGGCAAAATTATCAGTGAATT
CTCTAAGTCAGACAGGTGGGAGTCTGTATATGGAAGCTGGGAGTACATTGGATTTTGTAACTCCACAACCACCACAACAGCCTCCTGCCGCTAATCAGTT
GATCACGCTTTCCAATCTGCATTTGTCTCTTTCTTCTTTGTTAGCAAACAATGCAGTTACGAATCCTCCTACCAATCCTCCAGCGCAAGATTCTCATCCT
GCAATCATTGGTAGCACAACTGCTGGTTCTGTTACAATTAGTGGGCCTATCTTTTTTGAGGATTTGGATGATACAGCTTATGATAGGTATGATTGGCTAG
GTTCTAATCAAAAAATCGATGTCCTGAAATTACAGTTAGGGACTCAGCCCTCAGCTAATGCCCCATCAGATTTGACTCTAGGGAATGAGATGCCTAAGTA
TGGCTATCAAGGAAGCTGGAAGCTTGCGTGGGATCCTAATACAGCAAATAATGGTCCTTATACTCTGAAAGCTACATGGACTAAAACTGGGTATAATCCT
GGGCCTGAGCGAGTAGCTTCTTTGGTTCCAAATAGTTTATGGGGATCCATTTTAGATATACGATCTGCGCATTCAGCAATTCAAGCAAGTGTGGATGGGC
GCTCTTATTGTCGAGGATTATGGGTTTCTGGAGTTTCGAATTTCTTCTATCATGACCGCGATGCTTTAGGTCAGGGATATCGGTATATTAGTGGGGGTTA
TTCCTTAGGAGCAAACTCCTACTTTGGATCATCGATGTTTGGTCTAGCATTTACCGAAGTATTTGGTAGATCTAAAGATTATGTAGTGTGTCGTTCCAAT
CATCATGCTTGCATAGGATCCGTTTATCTATCTACCAAACAAGCTTTATGTGGATCCTATTTGTTCGGAGATGCGTTTATCCGTGCTAGCTACGGGTTTG
GGAACCAGCATATGAAAACCTCATACACATTTGCAGAGGAGAGCGATGTTCGTTGGGATAATAACTGTCTGGTTGGAGAGATTGGAGTGGGATTACCGAT
TGTGATTACTCCATCTAAGCTCTATTTGAATGAGTTGCGTCCTTTCGTGCAAGCTGAGTTTTCTTATGCCGATCATGAATCTTTTACAGAGGAAGGCGAT
CAAGCTCGGGCATTCAGGAGTGGACATCTCATGAATCTATCAGTTCCTGTTGGAGTAAAATTTGATCGATGTTCTAGTACACACCCTAATAAATATAGCT
TTATGGGGGCTTATATCTGTGATGCTTATCGCACCATCTCTGGGACTCAGACAACACTCCTATCCCATCAAGAGACATGGACAACAGATGCCTTTCATTT
GGCAAGACATGGAGTCATAGTTAGAGGGTCTATGTATGCTTCTCTAACAAGCAATATAGAAGTATATGGCCATGGAAGATATGAGTATCGAGATACTTCT
CGAGGTTATGGTTTGAGTGCAGGAAGTAAAGTCCGGTTCTAA
SEQ ID 11:
MNRVIEIHAHYDQRQLSQSPNTNFLVHHPYLTLIPKFLLGALIVYAPYSEAEMELAISGHKQGKDRDTFTMISSCPEGTNYIINRKLILSDFSLLNKVSS
GGAFRNLAGKISFLGKNSSASIHFKHININGFGAGVFSESSIEFTDLRKLVAFGSESTGGIFTAKEDISFKNNHHIAFRNNITKGNGGVIQLQGDMKGSV
SFVDQRGAIIFTNNQAVTSSSMKHSGRGGAISGDFAGSRILFLNNQQITFEGNSAVHGGAIYNKNGLVEFLGNAGPLAFKENTTIANGGAIYTSNFKANQ
QTSPILFSQNHANKKGGAIYAQYVNLEQNQDTIRFEKNTAKEGGGAITSSQCSITAHNTIIFSDNAAGDLGGGAILLEGKKPSLTLIAHSGNIAFSGNTM
LHITKKASLDRHNSILIKEAPYKIQLAANKNHSIHFFDPVMALSASSSPIQINAPEYETPFFSPKGMIVFSGANLLDDAREDVANRTSIFNQPVHLYNGT
LSIENGAHLIVQSFKQTGGRISLSPGSSLALYTMNSFFHGNISSKEPLEINGLSFGVDISPSNLQAEIRAGNAPLRLSGSPSIHDPEGLFYENRDTAASP
YQMEILLTSDKIVDISKFTTDSLVTNKQSGFQGAWHFSWQPNTINNTKQKILRASWLPTGEYVLESNRVGRAVPNSLWSTFLLLQTASHNLGDHLCNNRS
LIPTSYFGVLIGGTGAEMSTHSSEEESFISRLGATGTSIIRLTPSLTLSGGGSHMFGDSFVADLPEHITSEGIVQNVGLTHVWGPLTVNSTLCAALDHNA
MVRICSKKDHTYGKWDTFGMRGTLGASYTFLEYDQTMRVFSFANIEATNILQRAFTETGYNPRSFSKTKLLNIAIPIGIGYEFCLGNSSFALLGKGSIGY
SRDIKRENPSTLAHLAMNDFAWTTNGCSVPTSAHTLANQLILRYKACSLYITAYTINREGKNLSNSLSCGGYVGF
SEQ ID 12:
ATGAATCGAGTTATAGAAATCCATGCTCACTACGATCAAAGACAACTTTCTCAATCTCCAAATACAAACTTCTTAGTACATCATCCTTATCTTACTCTTA
TTCCCAAGTTTCTACTAGGAGCTCTAATCGTCTATGCTCCTTATTCGTTTGCAGAAATGGAATTAGCTATTTCTGGACATAAACAAGGTAAAGATCGAGA
TACCTTTACCATGATCTCTTCCTGTCCTGAAGGCACTAATTACATCATCAATCGCAAACTCATACTCAGTGATTTCTCGTTACTAAATAAAGTTTCATCA
GGGGGAGCCTTTCGGAATCTAGCAGGGAAAATTTCCTTCTTAGGAAAAAATTCTTCTGCGTCCATTCATTTTAAACACATTAATATCAATGGTTTTGGAG
CCGGAGTCTTTTCTGAATCCTCTATTGAATTTACTGATTTACGAAAACTTGTTGCTTTTGGATCTGAAAGCACAGGAGGAATTTTTACTGCGAAAGAGGA
CATCTCTTTTAAAAACAACCACCACATTGCCTTCCGCAATAATATCACCAAAGGGAATGGTGGCGTTATCCAGCTCCAAGGAGATATGAAAGGAAGCGTA
TCCTTTGTAGATCAACGTGGAGCTATCATCTTTACCATAAACCAAGCTGTAACTTCTTCATCAATGAAACATAGTGGTCGTGGAGGAGCAATTAGCGGTG
ACTTCGCAGGATCCAGAATTCTTTTTCTTAATAACCAACAAATTACTTTCGAAGGCAATAGCGCTGTGCATGGAGGTGCTATCTACAATAAGAATGGCCT
TGTCGAGTTCTTAGGAAATGCAGGACCTCTTGCCTTTAAAGAGAACACAACAATAGCTAACGGGGGAGCTATATACACAAGTAATTTCAAAGCGAATCAA
CAAACATCCCCCATTCTATTCTCTCAAAATCATGCGAATAAGAAAGGCGGAGCGATTTACGCGCAATATGTGAACTTAGAACAGAATCAAGATACTATTC
GCTTTGAAAAAAATACCGCTAAAGAAGGCGGTGGAGCCATCACCTCTTCTCAATGCTCAATTACTGCTCATAATACCATCATTTTTTCCGATAATGCTGC
CGGAGATCTTGGAGGAGGAGCAATTCTTCTAGAAGGGAAAAAACCTTCTCTAACCTTGATTGCTCATAGTGGTAATATTGCATTTAGCGGCAATACCATG
CTTCATATCACCAAAAAAGCTTCCCTAGATCGACACAATTCTATCTTAATCAAAGAAGCTCCCTATAAAATCCAACTTGCAGCGAACAAAAACCATTCTA
TTCATTTCTTTGATCCTGTCATGGCATTGTCAGCATCATCTTCCCCTATACAAATCAATGCTCCTGAGTATGAAACTCCCTTCTTCTCACCTAAGGGTAT
GATCGTTTTCTCGGGTGCGAATCTTTTAGATGATGCTAGGGAAGATGTTGCAAATAGAACATCGATTTTTAACCAACCCGTTCATCTATATAATGGCACC
CTATCTATCGAAAATGGAGCCCATCTGATTGTCCAAAGCTTCAAACAGACCGGAGGACGTATCAGTTTATCTCCAGGATCCTCCTTGGCTCTATACACGA
TGAACTCGTTCTTCCATGGCAACATATCCAGCAAAGAACCCCTAGAAATTAATGGTTTAAGCTTTGGAGTAGATATCTCTCCTTCTAATCTTCAAGCAGA
GATCCGTGCCGGCAACGCTCCTTTACGATTATCCGGATCCCCATCTATCCATGATCCTGAAGGATTATTCTACGAAAATCGCGATACTGCAGCATCACCA
TACCAAATGGAAATCTTGCTCACCTCTGATAAAATTGTAGATATCTCCAAATTTACTACTGATTCTCTAGTTACGAACAAACAATCAGGATTCCAAGGAG
CCTGGCATTTTAGCTGGCAGCCAAATACTATAAACAATACTAAACAAAAAATATTAAGAGCTTCTTGGCTCCCAACAGGAGAATATGTCCTTGAATCCAA
TCGAGTGGGGCGTGCCGTTCCTAATTCCTTATGGAGCACATTTTTACTTTTACAGACAGCCTCTCATAACTTAGGCGATCATCTATGTAATAATCGATCT
CTTATTCCTACTTCATACTTCGGAGTTTTAATTGGAGGAACTGGAGCAGAAATGTCTACCCACTCCTCAGAAGAAGAAAGCTTTATATCTCGTTTAGGAG
CTACAGGAACCTCTATCATACGCTTAACTCCCTCCCTGACACTCTCTGGAGGAGGCTCACATATGTTCGGAGATTCGTTCGTTGCAGACTTACCAGAACA
CATCACTTCAGAAGGAATTGTTCAGAATGTCGGTTTAACCCATGTCTGGGGACCCCTTACTGTCAATTCTACATTATGTGCAGCCTTAGATCACAACGCG
ATGGTCCGCATATGCTCCAAAAAAGATCACACCTATGGGAAATGGGATACATTCGGTATGCGAGGAACATTAGGAGCCTCTTATACATTCCTAGAATATG
ATCAAACTATGCGCGTATTCTCATTCGCCAACATCGAAGCCACAAATATCTTGCAAAGAGCTTTTACTGAAACAGGCTATAACCCAAGAAGTTTTTCCAA
GACAAAACTTCTAAACATCGCCATCCCCATAGGGATTGGTTATGAATTCTGCTTAGGGAATAGCTCTTTTGCTCTACTAGGTAAGGGATCCATCGGTTAC
TCTCGAGATATTAAACGAGAAAACCCATCCACTCTTGCTCACCTGGCTATGAATGATTTTGCTTGGACTACCAATGGCTGTTCAGTTCCAACCTCTGCAC
ACACATTGGCAAATCAATTGATTCTTCGCTATAAAGCATGTTCCTTATACATCACGGCATATACTATCAACCGTGAAGGGAAGAACCTCTCCAATAGCTT
ATCCTGCGGAGGCTATGTTGGCTTCTAA
SEQ ID 13:
MQTSFHKFFLSMILAYSCCSLSGGGYAAEIMIPQGIYDGETLTVSFPYTVIGDPSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLTF
ENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATTNNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAIDAKSLTVQ
GISKLCVFQENTAQADGGACQVVTSFSAMANEAPIAFIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFDGNVARVGGGIYSYGNVAFL
NNGKTLFLNNVASPVYIAAEQPTNGQASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSSNVAAGKGGAIYAKKLSVANCGPVQFLGNIAN
DGGAIYLGESGELSLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKITTLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTG
DIVFANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGSTLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPPAQDSHP
AIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKIDVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTANNGPYTLKATWTKTGYNP
GPERVASLVPNSLWGSILDIRSAHSAIQASVDGRSYCRGLWVSGVSNFFYHDRDALGQGYRYISGGYSLGANSYFGSSMFGLAFTEVFGRSKDYVVCRSN
HHACIGSVYLSTKQALCGSYLFGDAFIRASYGFGNQHMKTSYTFAEESDVRWDNNCLVGEIGVGLPIVITPSKLYLNELRPFVQAEFSYADHESFTEEGD
QARAFRSGHLMNLSVPVGVKFDRCSSTHPNKYSFMGAYICDAYRTISGTQTTLLSHQETWTTDAFHLARHGVIVRGSMYASLTSNIEVYGHGRYEYRDTS
RGYGLSAGSKVRF
SEQ ID 14:
ATGCAAACGTCTTTCCATAAGTTCTTTCTTTCAATGATTCTAGCTTATTCTTGCTGCTCTTTAAGTGGGGGGGGGTATGCAGCAGAAATCATGATTCCTC
AAGGAATTTACGATGGGGAGACGTTAACTGTATCATTTCCCTATACTGTTATAGGAGATCCGAGTGGGACTACTGTTTTTTCTGCAGGAGAGTTAACGTT
AAAAAATCTTGACAATTCTATTGCAGCTTTGCCTTTAAGTTGTTTTGGGAACTTATTAGGGAGTTTTACTGTTTTAGGGAGAGGACACTCGTTGACTTTC
GAGAACATACGGACTTCTACAAATGGAGCTGCACTAAGTGACAGCGCTAATAGCGGGTTATTTACTATTGAGGGTTTTAAAGAATTATCTTTTTCCAATT
GCAACTCATTACTTGCCGTACTGCCTGCTGCAACGACTAATAATGGTAGCCAGACTCCGACGACAACATCTACACCGTCTAATGGTACTATTTATTCTAA
AACAGATCTTTTGTTACTCAATAATGAGAAGTTCTCATTCTATAGTAATTTAGTCTCTGGAGATGGGGGAGCTATAGATGCTAAGAGCTTAACGGTTCAA
GGAATTAGCAAGCTTTGTGTCTTCCAAGAAAATACTGCTCAAGCTGATGGGGGAGCTTGTCAAGTAGTCACCAGTTTCTCTGCTATGGCTAACGAGGCTC
CTATTGCCTTTATAGCGAATGTTGCAGGAGTAAGAGGGGGAGGGATTGCTGCTGTTCAGGATGGGCAGCAGGGAGTGTCATCATCTACTTCAACAGAAGA
TCCAGTAGTAAGTTTTTCCAGAAATACTGCGGTAGAGTTTGATGGGAACGTAGCCCGAGTAGGAGGAGGGATTTACTCCTACGGGAACGTTGCTTTCCTG
AATAATGGAAAAACCTTGTTTCTCAACAATGTTGCTTCTCCTGTTTACATTGCTGCTGAGCAACCAACAAATGGACAGGCTTCTAATACGAGTGATAATT
ACGGAGATGGAGGAGCTATCTTCTGTAAGAATGGTGCGCAAGCAGCAGGATCCAATAACTCTGGATCAGTTTCCTTTGATGGAGAGGGAGTAGTTTTCTT
TAGTAGCAATGTAGCTGCTGGGAAAGGGGGAGCTATTTATGCCAAAAAGCTCTCGGTTGCTAACTGTGGCCCTGTACAATTCTTAGGGAATATCGCTAAT
GATGGTGGAGCGATTTATTTAGGAGAATCTGGAGAGCTCAGTTTATCTGCTGATTATGGAGATATTATTTTCGATGGGAATCTTAAAAGAACAGCCAAAG
AGAATGCTGCCGATGTTAATGGCGTAACTGTGTCCTCACAAGCCATTTCGATGGGATCGGGAGGGAAAATAACGACATTAAGAGCTAAAGCAGGGCATCA
GATTCTCTTTAATGATCCCATCGAGATGGCAAACGGAAATAACCAGCCAGCGCAGTCTTCCGAACCTCTAAAAATTAACGATGGTGAAGGATACACAGGG
GATATTGTTTTTGCTAATGGAAACAGTACTTTGTACCAAAATGTTACGATAGAGCAAGGAAGGATTGTTCTTCGTGAAAAGGCAAAATTATCAGTGAATT
CTCTAAGTCAGACAGGTGGGAGTCTGTATATGGAAGCTGGGAGTACATTGGATTTTGTAACTCCACAACCACCACAACAGCCTCCTGCCGCTAATCAGTT
GATCACGCTTTCCAATCTGCATTTGTCTCTTTCTTCTTTGTTAGCAAACAATGCAGTTACGAATCCTCCTACCAATCCTCCAGCGCAAGATTCTCATCCT
GCAATCATTGGTAGCACAACTGCTGGTTCTGTTACAATTAGTGGGCCTATCTTTTTTGAGGATTTGGATGATACAGCTTATGATAGGTATGATTGGCTAG
GTTCTAATCAAAAAATCGATGTCCTGAAATTACAGTTAGGGACTCAGCCCTCAGCTAATGCCCCATCAGATTTGACTCTAGGGAATGAGATGCCTAAGTA
TGGCTATCAAGGAAGCTGGAAGCTTGCGTGGGATCCTAATACAGCAAATAATGGTCCTTATACTCTGAAAGCTACATGGACTAAAACTGGGTATAATCCT
GGGCCTGAGCGAGTAGCTTCTTTGGTTCCAAATAGTTTATGGGGATCCATTTTAGATATACGATCTGCGCATTCAGCAATTCAAGCAAGTGTGGATGGGC
GCTCTTATTGTCGAGGATTATGGGTTTCTGGAGTTTCGAATTTCTTCTATCATGACCGCGATGCTTTAGGTCAGGGATATCGGTATATTAGTGGGGGTTA
TTCCTTAGGAGCAAACTCCTACTTTGGATCATCGATGTTTGGTCTAGCATTTACCGAAGTATTTGGTAGATCTAAAGATTATGTAGTGTGTCGTTCCAAT
CATCATGCTTGCATAGGATCCGTTTATCTATCTACCAAACAAGCTTTATGTGGATCCTATTTGTTCGGAGATGCGTTTATCCGTGCTAGCTACGGGTTTG
GGAACCAGCATATGAAAACCTCATACACATTTGCAGAGGAGAGCGATGTTCGTTGGGATAATAACTGTCTGGTTGGAGAGATTGGAGTGGGATTACCGAT
TGTGATTACTCCATCTAAGCTCTATTTGAATGAGTTGCGTCCTTTCGTGCAAGCTGAGTTTTCTTATGCCGATCATGAATCTTTTACAGAGGAAGGCGAT
CAAGCTCGGGCATTCAGGAGTGGACATCTCATGAATCTATCAGTTCCTGTTGGAGTAAAATTTGATCGATGTTCTAGTACACACCCTAATAAATATAGCT
TTATGGGGGCTTATATCTGTGATGCTTATCGCACCATCTCTGGGACTCAGACAACACTCCTATCCCATCAAGAGACATGGACAACAGATGCCTTTCATTT
GGCAAGACATGGAGTCATAGTTAGAGGGTCTATGTATGCTTCTCTAACAAGCAATATAGAAGTATATGGCCATGGAAGATATGAGTATCGAGATACTTCT
CGAGGTTATGGTTTGAGTGCAGGAAGTAAAGTCCGGTTCTAA
SEQ ID 15:
MKKAFFFFLIGNSLSGLAREVPSRIFLMPNSVPDPTKESLSNKISLTGDTHNLTNCYLDNLRYILAILQKTPNEGAAVTITDYLSFFDTQKEGIYFAKNL
TPESGGAIGYASPNSPTVEIRDTIGPVIFENNTCCRLFTWRNPYAADKIREGGAIHAQNLYINHNHDVVGFMKNFSYVQGGAISTANTFVVSENQSCFLF
MDNICIQTNTAGKGGAIYAGTSNSFESNNCDLFFINNACCAGGAIFSPICSLTGNRGNIVFYNNRCFKNNETASSEASDGGAIKVTTRLDVTGNRGRIFF
SDNITKNYGGAIYAPVVTLVDNGPTYFINNIANNKGGAIYIDGTSNSKISADRHAIIFNENIVTNVTNANGTSTSANPPRRNAITVASSSGEILLGAGSS
QNLIFYDPIEVSNAGVSVSFNKEADQTGSVVFSGATVNSADFHQRNLQTKTPAPLTLSNGFLCIEDHAQLTVNRFTQTGGVVSLGNGAVLSCYKNGTGDS
ASNASITLKHIGLNLSSILKSGAEIPLLWVEPTNNSNNYTADTAATFSLSDVKLSLIDDYGNSPYESTDLTHALSSQPMLSISEASDNQLQSENIDFSGL
NVPHYGWQGLWTWGWAKTQDPEPASSATITDPQKANRFHRTLLLTWLPAGYVPSPKHRSPLIANTLWGNMLLATESLKNSAELTPSGHPFWGITGGGLGM
MVYQDPRENHPGFHMRSSGYSAGMIAGQTHTFSLKFSQTYTKLNERYAKNNVSSKNYSCQGEMLFSLQEGFLLTKLVGLYSYGDHNCHHFYTQGENLTSQ
GTFRSQTMGGAVFFDLPMKPFGSTHILTAPFLGALGIYSSLSHFTEVGAYPRSFSTKTPLINVLVPIGVKGSFMNATHRPQAWTVELAYQPVLYRQEPGI
AAQLLASKGIWFGSGSPSSRHAMSYKISQQTQPLSWLTLHFQYHGFYSSSTFCNYLNGEIALRF
SEQ ID 16:
ATGAAAAAAGCGTTTTTCTTTTTCCTTATCGGAAACTCCCTATCAGGACTAGCTAGAGAGGTTCCTTCTAGAATCTTTCTTATGCCCAACTCAGTTCCAG
ATCCTACGAAAGAGTCGCTATCAAATAAAATTAGTTTGACAGGAGACACTCACAATCTCACTAACTGCTATCTCGATAACCTACGCTACATACTGGCTAT
TCTACAAAAAACTCCCAATGAAGGAGCTGCTGTCACAATAACAGATTACCTAAGCTTTTTTGATACACAAAAAGAAGGTATTTATTTTGCAAAAAATCTC
ACCCCTGAAAGTGGTGGTGCGATTGGTTATGCGAGTCCCAATTCTCCTACCGTGGAGATTCGTGATACAATAGGTCCTGTAATCTTTGAAAATAATACTT
GTTGCAGACTATTTACATGGAGAAATCCTTATGCTGCTGATAAAATAAGAGAAGGCGGAGCCATTCATGCTCAAAATCTTTACATAAATCATAATCATGA
TGTGGTCGGATTTATGAAGAACTTTTCTTATGTCCAAGGAGGAGCCATTAGTACCGCTAATACCTTTGTTGTGAGCGAGAATCAGTCTTGTTTTCTCTTT
ATGGACAACATCTGTATTCAAACTAATACAGCAGGAAAAGGTGGCGCTATCTATGCTGGAACGAGCAATTCTTTTGAGAGTAATAACTGCGATCTCTTCT
TCATCAATAACGCCTGTTGTGCAGGAGGAGCGATCTTCTCCCCTATCTGTTCTCTAACAGGAAATCGTGGTAACATCGTTTTCTATAACAATCGCTGCTT
TAAAAATGTAGAAACAGCTTCTTCAGAAGCTTCTGATGGAGGAGCAATTAAAGTAACTACTCGCCTAGATGTTACAGGCAATCGTGGTAGGATCTTTTTT
AGTGACAATATCACAAAAAATTATGGCGGAGCTATTTACGCTCCTGTAGTTACCCTAGTGGATAATGGCCCTACCTACTTTATAAACAATATCGCCAATA
ATAAGGGGGGCGCTATCTATATAGACGGAACCAGTAACTCCAAAATTTCTGCCGACCGCCATGCTATTATTTTTAATGAAAATATTGTGACTAATGTAAC
TAATGCAAATGGTACCAGTACGTCAGCTAATCCTCCTAGAAGAAATGCAATAACAGTAGCAAGCTCCTCTGGTGAAATTCTATTAGGAGCAGGGAGTAGC
CAAAATTTAATTTTTTATGATCCTATTGAAGTTAGCAATGCAGGGGTCTCTGTGTCCTTCAATAAGGAAGCTGATCAAACAGGCTCTGTAGTATTTTCAG
GAGCTACTGTTAATTCTGCAGATTTTCATCAACGCAATTTACAAACAAAAACACCTGCACCCCTTACTCTCAGTAATGGTTTTCTATGTATCGAAGATCA
TGCTCAGCTTACAGTGAATCGATTCACACAAACTGGGGGTGTTGTTTCTCTTGGGAATGGAGCAGTTCTGAGTTGCTATAAAAATGGTACAGGAGATTCT
GCTAGCAATGCCTCTATAACACTGAAGCATATTGGATTGAATCTTTCTTCCATTCTGAAAAGTGGTGCTGAGATTCCTTTATTGTGGGTAGAGCCTACAA
ATAACAGCAATAACTATACAGCAGATACTGCAGCTACCTTTTCATTAAGTGATGTAAAACTCTCACTCATTGATGACTACGGGAACTCTCCTTATGAATC
CACAGATCTGACCCATGCTCTGTCATCACAGCCTATGCTATCTATTTCTGAAGCTAGCGATAACCAGCTACAATCAGAAAATATAGATTTTTCGGGACTA
AATGTCCCTCATTATGGATGGCAAGGACTTTGGACTTGGGGCTGGGCAAAAACTCAAGATCCAGAACCAGCATCTTCAGCAACAATCACTGATCCACAAA
AAGCCAATAGATTTCATAGAACCTTACTACTAACATGGCTTCCTGCCGGGTATGTTCCTAGCCCAAAACACAGAAGTCCCCTCATAGCTAACACCTTATG
GGGGAATATGCTGCTTGCAACAGAAAGCTTAAAAAATAGTGCAGAGCTGACACCTAGTGGTCATCCTTTCTGGGGAATTACAGGAGGAGGACTAGGCATG
ATGGTTTACCAAGATCCTCGAGAAAATCATCCTGGATTCCATATGCGCTCTTCCGGATACTCTGCGGGGATGATAGCAGGGCAGACACACACCTTCTCAT
TGAAATTCAGTCAGACCTACACCAAACTCAATGAGCGTTACGCAAAAAACAACGTATCTTCTAAAAATTACTCATGCCAAGGAGAAATGCTCTTCTCATT
GCAAGAAGGTTTCTTGCTGACTAAATTAGTTGGGCTTTACAGCTATGGAGACCATAACTGTCACCATTTCTATACTCAAGGAGAAAATCTAACATCTCAA
GGGACGTTCCGCAGTCAAACGATGGGAGGTGCTGTCTTTTTTGATCTCCCTATGAAACCCTTTGGATCAACGCATATACTGACAGCTCCCTTTTTAGGTG
CTCTTGGTATTTATTCTAGCCTGTCTCACTTTACTGAGGTGGGAGCCTATCCGCGAAGCTTTTCTACAAAGACTCCTTTGATCAATGTCCTAGTCCCTAT
TGGAGTTAAAGGTAGCTTTATGAATGCTACCCACAGACCTCAAGCCTGGACTGTAGAATTGGCATACCAACCCGTTCTGTATAGACAAGAACCAGGGATC
GCAGCCCAGCTCCTAGCCAGTAAGGGTATTTGGTTCGGTAGTGGAAGCCCCTCATCGCGTCATGCCATGTCCTATAAAATCTCACAGCAAACACAACCTT
TGAGTTGGTTAACTCTCCATTTCCAGTATCATGGATTCTACTCCTCTTCAACCTTCTGTAATTATCTCAATGGGGAAATTGCTCTGCGATTCTAG
SEQ ID 17:
MQTSFHKFFLSMILAYSCCSLSGGGYAAEIMIPQGIYDGETLTVSFPYTVIGDPSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLTF
ENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATTNNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAIDAKSTTVQ
GTSKLCVFQENTAQADGGACQVVTSFSAMANEAPIAFIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFDGNVARVGGGIYSYGNVAFL
NNGKTLFLNNVASPVYIAAEQPTNGQASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSSNVAAGKGGAIYAKKLSVANCGPVQFLGNIAN
DGGAIYLGESGELSLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKITTLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTG
DIVFANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGSTLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPPAQDSHP
AIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKIDVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTANNGPYTLKATWTKTGYNP
GPERVASLVPNSLWGSILDIRSAHSAIQASVDGRSYCRGLWVSGVSNFFYHDRDALGQGYRYISGGYSLGANSYFGSSMFGLAFTEVFGRSKDYVVCRSN
HHACIGSVYLSTKQALCGSYLFGDAFIRASYGFGNQHMKTSYTFAEESDVRWDNNCLVGEIGVGLPIVITPSKLYLNELRPFVQAEFSYADHESFTEEGD
QARAFRSGHLMNLSVPVGVKFDRCSSTHPNKYSFMGAYICDAYRTISGTQTTLLSHQETWTTDAFHLARHGVIVRGSMYASLTSNIEVYGHGRYEYRDTS
RGYGLSAGSKVRF
SEQ ID 18:
ATGCAAACGTCTTTCCATAAGTTCTTTCTTTCAATGATTCTAGCTTATTCTTGCTGCTCTTTAAGTGGGGGGGGGTATGCAGCAGAAATCATGATTCCTC
AAGGAATTTACGATGGGGAGACGTTAACTGTATCATTTCCCTATACTGTTATAGGAGATCCGAGTGGGACTACTGTTTTTTCTGCAGGAGAGTTAACGTT
AAAAAATCTTGACAATTCTATTGCAGCTTTGCCTTTAAGTTGTTTTGGGAACTTATTAGGGAGTTTTACTGTTTTAGGGAGAGGACACTCGTTGACTTTC
GAGAACATACGGACTTCTACAAATGGAGCTGCACTAAGTGACAGCGCTAATAGCGGGTTATTTACTATTGAGGGTTTTAAAGAATTATCTTTTTCCAATT
GCAACTCATTACTTGCCGTACTGCCTGCTGCAACGACTAATAATGGTAGCCAGACTCCGACGACAACATCTACACCGTCTAATGGTACTATTTATTCTAA
AACAGATCTTTTGTTACTCAATAATGAGAAGTTCTCATTCTATAGTAATTTAGTCTCTGGAGATGGGGGAGCTATAGATGCTAAGAGCTTAACGGTTCAA
GGAATTAGCAAGCTTTGTGTCTTCCAAGAAAATACTGCTCAAGCTGATGGGGGAGCTTGTCAAGTAGTCACCAGTTTCTCTGCTATGGCTAACGAGGCTC
CTATTGCCTTTATAGCGAATGTTGCAGGAGTAAGAGGGGGAGGGATTGCTGCTGTTCAGGATGGGCAGCAGGGAGTGTCATCATCTACTTCAACAGAAGA
TCCAGTAGTAAGTTTTTCCAGAAATACTGCGGTAGAGTTTGATGGGAACGTAGCCCGAGTAGGAGGAGGGATTTACTCCTACGGGAACGTTGCTTTCCTG
AATAATGGAAAAACCTTGTTTCTCAACAATGTTGCTTCTCCTGTTTACATTGCTGCTGAGCAACCAACAAATGGACAGGCTTCTAATACGAGTGATAATT
ACGGAGATGGAGGAGCTATCTTCTGTAAGAATGGTGCGCAAGCAGCAGGATCCAATAACTCTGGATCAGTTTCCTTTGATGGAGAGGGAGTAGTTTTCTT
TAGTAGCAATGTAGCTGCTGGGAAAGGGGGAGCTATTTATGCCAAAAAGCTCTCGGTTGCTAACTGTGGCCCTGTACAATTCTTAGGGAATATCGCTAAT
GATGGTGGAGCGATTTATTTAGGAGAATCTGGAGAGCTCAGTTTATCTGCTGATTATGGAGATATTATTTTCGATGGGAATCTTAAAAGAACAGCCAAAG
AGAATGCTGCCGATGTTAATGGCGTAACTGTGTCCTCACAAGCCATTTCGATGGGATCGGGAGGGAAAATAACGACATTAAGAGCTAAAGCAGGGCATCA
GATTCTCTTTAATGATCCCATCGAGATGGCAAACGGAAATAACCAGCCAGCGCAGTCTTCCGAACCTCTAAAAATTAACGATGGTGAAGGATACACAGGG
GATATTGTTTTTGCTAATGGAAACAGTACTTTGTACCAAAATGTTACGATAGAGCAAGGAAGGATTGTTCTTCGTGAAAAGGCAAAATTATCAGTGAATT
CTCTAAGTCAGACAGGTGGGAGTCTGTATATGGAAGCTGGGAGTACATTGGATTTTGTAACTCCACAACCACCACAACAGCCTCCTGCCGCTAATCAGTT
GATCACGCTTTCCAATCTGCATTTGTCTCTTTCTTCTTTGTTAGCAAACAATGCAGTTACGAATCCTCCTACCAATCCTCCAGCGCAAGATTCTCATCCT
GCAATCATTGGTAGCACAACTGCTGGTTCTGTTACAATTAGTGGGCCTATCTTTTTTGAGGATTTGGATGATACAGCTTATGATAGGTATGATTGGCTAG
GTTCTAATCAAAAAATCGATGTCCTGAAATTACAGTTAGGGACTCAGCCCTCAGCTAATGCCCCATCAGATTTGACTCTAGGGAATGAGATGCCTAAGTA
TGGCTATCAAGGAAGCTGGAAGCTTGCGTGGGATCCTAATACAGCAAATAATGGTCCTTATACTCTGAAAGCTACATGGACTAAAACTGGGTATAATCCT
GGGCCTGAGCGAGTAGCTTCTTTGGTTCCAAATAGTTTATGGGGATCCATTTTAGATATACGATCTGCGCATTCAGCAATTCAAGCAAGTGTGGATGGGC
GCTCTTATTGTCGAGGATTATGGGTTTCTGGAGTTTCGAATTTCTTCTATCATGACCGCGATGCTTTAGGTCAGGGATATCGGTATATTAGTGGGGGTTA
TTCCTTAGGAGCAAACTCCTACTTTGGATCATCGATGTTTGGTCTAGCATTTACCGAAGTATTTGGTAGATCTAAAGATTATGTAGTGTGTCGTTCCAAT
CATCATGCTTGCATAGGATCCGTTTATCTATCTACCAAACAAGCTTTATGTGGATCCTATTTGTTCGGAGATGCGTTTATCCGTGCTAGCTACGGGTTTG
GGAACCAGCATATGAAAACCTCATACACATTTGCAGAGGAGAGCGATGTTCGTTGGGATAATAACTGTCTGGTTGGAGAGATTGGAGTGGGATTACCGAT
TGTGATTACTCCATCTAAGCTCTATTTGAATGAGTTGCGTCCTTTCGTGCAAGCTGAGTTTTCTTATGCCGATCATGAATCTTTTACAGAGGAAGGCGAT
CAAGCTCGGGCATTCAGGAGTGGACATCTCATGAATCTATCAGTTCCTGTTGGAGTAAAATTTGATCGATGTTCTAGTACACACCCTAATAAATATAGCT
TTATGGGGGCTTATATCTGTGATGCTTATCGCACCATCTCTGGGACTCAGACAACACTCCTATCCCATCAAGAGACATGGACAACAGATGCCTTTCATTT
GGCAAGACATGGAGTCATAGTTAGAGGGTCTATGTATGCTTCTCTAACAAGCAATATAGAAGTATATGGCCATGGAAGATATGAGTATCGAGATACTTCT
CGAGGTTATGGTTTGAGTGCAGGAAGTAAAGTCCGGTTCTAA
SEQ ID 19:
MQLPSIIQSFFFPKAPPSPLKKPIYQQTERIINIAYLVLLSLSVVGIISGVFLSLSFPLLGAGICLISLAVGSCLLVLFPLLPDIEKIIARREPKVSITT
SSPLPTLMRYFKSIGLGKAAH
SEQ ID 20:
ATGCAACTTCCGTCTATTATTCAGTCTTTCTTCTTCCCTAAAGCTCCCCCATCTCCACTTAAAAAACCTATTTATCAACAAACTGAACGCATCATCAATA
TAGCTTATCTTGTTCTGTTATCCCTATCCGTTGTAGGAATTATCTCTGGAGTATTCCTTTCCCTTAGCTTCCCCCTATTAGGCGCAGGCATTTGTTTAAT
CTCTTTAGCCGTAGGTTCCTGCCTACTTGTTTTGTTTCCATTGCTCCCGGATATTGAAAAAATAATTGCTCGAAGAGAACCCAAGGTCTCGATTACAACT
AGCTCCCCATTACCAACATTAATGCGCTACTTCAAATCGATTGGCCTTGGAAAAGCAGCTCATTAG
SEQ ID 21:
MHDALQSILAIQELDIKMIRLMRVKKEHQNELAKIQALKTDIRRKVEEKEQEMEKLKDQIKGGEKRIQEISDQINKLENQQAAVKKMDEFNALTQEMTAA
NKERRTLEHQLSDLMDKQAGSEDLLISLKESLSSTENSSSAIEEEIRENIRKINEEGRSLLSQRTQLKETTDPELFSIYERLLNNKKDRVVVPIENRVCS
GCHIALTPQHENLVRKQDHLVFCEHCSRILYWQELQSPSAEGATTKRRRRRTAV
SEQ ID 22:
ATGCATGACGCCCTCCAAAGTATTTTGGCTATCCAAGAGCTCGATATTAAAATGATCCGTTTAATGCGGGTCAAAAAAGAACATCAGAACGAGCTCGCTA
AAATTCAAGCTTTAAAAACGGATATCCGTCGCAAGGTGGAAGAAAAAGAACAAGAAATGGAGAAGCTGAAAGATCAGATCAAAGGCGGAGAAAAACGTAT
TCAAGAAATTTCTGATCAGATCAATAAATTAGAAAATCAGCAAGCTGCTGTAAAAAAAATGGATGAGTTTAATGCTCTAACCCAAGAGATGACCGCAGCT
AATAAAGAGCGTCGCACTTTGGAGCACCAACTTAGCGATCTTATGGATAAGCAAGCTGGTAGCGAAGATCTTCTTATCTCTCTGAAAGAAAGTCTCTCTT
CTACGGAAAATAGTAGCAGTGCTATCGAAGAAGAAATTCGAGAGAATATTCGAAAAATTAATGAAGAAGGTCGTTCTTTACTAAGTCAGAGAACACAGCT
GAAAGAAACGACAGATCCAGAATTATTTAGCATCTACGAGCGCTTGCTCAACAACAAGAAAGACCGAGTTGTTGTCCCTATCGAAAATCGTGTTTGCAGT
GGCTGTCATATAGCTCTTACCCCGCAACATGAGAATTTGGTACGTAAACAAGATCATCTTGTATTTTGTGAACACTGCTCAAGAATTCTTTACTGGCAAG
AGTTGCAATCTCCATCAGCAGAAGGCGCAACTACAAAACGTCGTCGTCGTCGTACTGCAGTATAA
SEQ ID 23:
MRPDHMNFCCLCAAILSSTAVLFGQDPLGETALLTKNPNHVVCTFFEDCTMESLFPALCAHASQDDPLYVLGNSYCWFVSKLHITDPKEALFKEKGDLSI
QNFRFLSFTDCSSKESSPSIIHQKNGQLSLRNNGSMSFCRNHAEGSGGAISADAFSLQHNYLFTAFEENSSKGNGGAIQAQTFSLSRNVSPISFARNRAD
LNGGAICCSNLICSGNVNPLFFTGNSATNGGAICCISDLNTSEKGSLSLACNQETLFASNSAKEKGGAIYAKHMVLRYNGPVSFINNSAKIGGAIAIQSG
GSLSILAGEGSVLFQNNSQRTSDQGLVRNAIYLEKDAILSSLEARNGDILFFDPIVQESSSKESPLPSSLQASVTSPTPATASPLVIQTSANRSVIFSSE
RLSEEEKTPDNLTSQLQQPIELKSGRLVLKDRAVLSAPSLSQDPQALLIMEAGTSLKTSSDLKLATLSIPLHSLDTEKSVTIHAPNLSIQKIFLSNSGDE
NFYENVELLSKEQNNIPLLTLSKEQSHLHLPDGNLSSHFGYQGDWTFSWKDSDEGHSLIANWTPKNYVPHPERQSTLVANTLWNTYSDMQAVQSMINTIA
HGGAYLFGTWGSAVSNLFYAHDSSGKPIDNWHHRSLGYLFGISTHSLDDHSFCLAAGQLLGKSSDSFITSTETTSYIATVQAQLATPLMKISAQACYNES
IHELKTKYRSFSKEGFGSWHSVAVSGEVCASIPIVSNGSGLFSSFSIFSKLQGFSGTQDGFEESSGEIRSFSASSFRNISLPMGITFEKKSQKTRNYYYF
LGAYIQDLKRDVESGPVVLLKNAVSWDAPMANLDSRAYMFRLTNQRALHRLQTLLNVSYVLRGQSHSYSLDLGTTYRF
SEQ ID 24:
ATGCGACCTGATCATATGAACTTCTGTTGTCTATGTGCTGCTATTTTGTCATCCACAGCGGTCCTCTTTGGCCAGGATCCCTTAGGTGAAACCGCCCTCC
TCACTAAAAATCCTAATCATGTCGTCTGTACATTTTTTGAGGACTGTACCATGGAGAGCCTCTTTCCTGCTCTTTGTGCTCATGCATCACAAGATGATCC
TTTGTATGTACTTGGAAATTCCTACTGTTGGTTCGTATCTAAACTCCATATCACGGACCCCAAAGAGGCTCTTTTTAAAGAAAAAGGAGATCTTTCCATT
CAAAATTTTCGCTTCCTTTCCTTCACAGATTGCTCTTCCAAGGAAAGCTCTCCTTCTATTATTCATCAAAAGAATGGTCAGTTATCCTTGCGCAATAATG
GTAGCATGAGTTTCTGTCGAAATCATGCTGAAGGCTCTGGAGGAGCCATCTCTGCGGATGCCTTTTCTCTACAACACAACTATCTTTTCACAGCTTTTGA
AGAGAATTCTTCTAAAGGAAATGGCGGAGCCATTCAGGCTCAAACCTTCTCTTTATCTAGAAATGTGTCGCCTATTTCTTTCGCCCGTAATCGTGCGGAT
TTAAATGGCGGCGCTATTTGCTGTAGTAATCTTATTTGTTCAGGGAATGTAAACCCTCTCTTTTTCACTGGAAACTCCGCCACGAATGGAGGCGCTATTT
GTTGTATCAGCGATCTAAACACCTCAGAAAAAGGCTCTCTCTCTCTTGCTTGTAACCAAGAAACGCTATTTGCAAGCAATTCTGCTAAAGAAAAAGGCGG
GGCTATTTATGCCAAGCACATGGTATTGCGTTATAACGGTCCTGTTTCCTTCATTAACAACAGCGCTAAAATAGGTGGAGCTATCGCCATCCAGTCCGGA
GGGAGTCTCTCTATCCTTGCAGGTGAAGGATCTGTTCTGTTCCAGAATAACTCCCAACGCACCTCCGACCAAGGTCTAGTAAGAAACGCCATCTACTTAG
AGAAAGATGCGATTCTTTCTTCCTTAGAAGCTCGCAACGGAGATATTCTTTTCTTTGATCCTATTGTACAAGAAAGTAGCAGCAAAGAATCGCCTCTTCC
CTCCTCTTTGCAAGCCAGCGTGACTTCTCCCACCCCAGCCACCGCATCTCCTTTAGTTATTCAGACAAGTGCAAACCGTTCAGTGATTTTCTCGAGCGAA
CGTCTTTCTGAAGAAGAAAAAACTCCTGATAACCTCACTTCCCAACTACAGCAGCCTATCGAACTGAAATCCGGACGCTTAGTTTTAAAAGATCGCGCTG
TCCTTTCCGCGCCTTCTCTCTCTCAGGATCCTCAAGCTCTCCTCATTATGGAAGCGGGAACTTCTTTAAAAACTTCCTCTGATTTGAAGTTAGCTACGCT
AAGTATTCCCCTTCATTCCTTAGATACTGAAAAAAGCGTAACTATCCACGCCCCTAACCTTTCTATCCAAAAGATCTTCCTCTCTAATTCTGGAGATGAG
AATTTTTATGAAAATGTAGAGCTTCTCAGTAAAGAGCAAAACAATATTCCTCTCCTTACTCTCTCTAAAGAGCAATCTCATTTACATCTTCCTGATGGGA
ACCTCTCTTCTCACTTTGGATATCAAGGAGATTGGACTTTTTCTTGGAAAGATTCTGATGAAGGGCATTCTCTGATTGCTAATTGGACGCCTAAAAACTA
TGTGCCTCATCCAGAACGTCAATCTACACTCGTTGCGAACACTCTTTGGAACACCTATTCCGATATGCAAGCTGTGCAGTCGATGATTAATACAATAGCG
CACGGAGGAGCCTATCTATTTGGAACGTGGGGATCTGCTGTTTCTAATTTATTCTATGCTCACGACAGCTCTGGGAAACCTATCGATAATTGGCATCATA
GAAGCCTTGGCTACCTATTCGGTATCAGTACTCACAGTTTAGATGACCATTCTTTCTGCTTGGCTGCAGGACAATTACTCGGGAAATCGTCCGATTCCTT
TATTACGTCTACAGAAACGACCTCCTATATAGCTACTGTACAAGCGCAACTCGCTACCCCTCTAATGAAAATCTCTGCACAGGCATGCTATAATGAAAGT
ATCCATGAGCTAAAAACAAAATATCGCTCCTTCTCTAAAGAAGGATTCGGATCCTGGCATAGCGTTGCAGTATCCGGAGAAGTGTGCGCATCGATTCCTA
TTGTATCCAATGGTTCCGGACTGTTCAGCTCCTTCTCTATTTTCTCTAAACTGCAAGGATTTTCAGGAACACAGGACGGTTTTGAGGAGAGTTCGGGAGA
GATTCGGTCCTTTTCTGCCAGCTCTTTCAGAAATATTTCACTTCCTATGGGAATAACATTTGAAAAAAAATCCCAAAAAACACGAAACTACTATTACTTT
CTGGGAGCCTACATCCAAGACCTAAAACGTGATGTGGAATCGGGACCTGTAGTGTTACTCAAAAATGCCGTCTCCTGGGATGCTCCTATGGCGAACTTGG
ATTCGCGAGCCTACATGTTCAGGCTTACGAATCAAAGAGCTCTGCATAGACTTCAGACGCTGTTAAATGTGTCTTACGTACTGCGCGGGCAAAGCCATAG
TTACTCCCTGGATCTGGGGACCACTTACAGGTTCTAG
SEQ ID 25:
MKRFFPLFIGVLLAHTLPSEGLSHQQAVQKKISYLSHFKGITGIMDVEDGVLHIHDDLRLQANKAYVENRTDCGIKIVAHGNVMVNYRGKILICDYLEYY
EDTDSCLLTNGRCSLYPWFIGGSTITISPSSIIIHKGYISTSEGPQKHICLSGDYLKYSSDSVLSMGPSRLSICNTPVLLLPQISIMPMEIPKPPITFRG
GSGGFLGSYLGVSYSPISKKHCSTTLFLDGFFKHGIGLGYNMRFSSQENPSNAINIKSYYAHRLAIDSSGAKDRYRLHGDFTFSKERAHLAGEFHLSDSW
ETVVDIFPNNFSLKNTGPTEVSLSWRDNNLFGKMTSSVKVNSFQNVKQELPQAILHHRPVRIRRSRIFLENRLEAGFLDFHFSSNIPGSNFSSWRFSSAH
KVYRGLVLPIGTLTPSLSGTAIYYTRMLSPNAAHCQLSGSLSFDYRVALQKEYRHARHIVEPFCSFLKTTRPVLSSDEPHIFSIKDAFHSINLLHVGLES
KVLNKHSTPSHLKLWTTYIFDEPHAKDTFPKTACWFSLPLTLQNTLSLDAEWIWKKSRWDHLNVIWEWILNDNLGLTLEFLHRSKYGFIKCAKDNYTLDV
SRSLDTLLASPLSDRRNLITGKLFVRPHPHWNYNLNLRYGWHRPDSPSYLEYQMILGHKIFEHWQLFSVYEKREADKRCFFYLKLDKRKQKHRHPFG
SEQ ID 26:
GTGAAACGATTTTTCCCACTTTTTATTGGAGTGCTGCTCGCGCACACTTTGCCGTCAGAAGGTCTTTCTCATCAACAAGCTGTCCAAAAAAAAATTTCTT
ATCTGAGCCATTTTAAAGGCATTACAGGAATTATGGATGTTGAGGATGGGGTATTACATATCCATGATGATCTACGTCTTCAAGCCAATAAAGCCTATGT
TGAAAATCGCACGGATTGTGGGATCAAAATCGTTGCTCATGGCAACGTTATGGTCAATTATCGCGGGAAAATTTTAATCTGTGATTATCTTGAGTACTAT
GAAGATACAGATTCTTGTTTACTCACCAATGGCCGCTGTTCGTTATACCCATGGTTCATTGGAGGATCCACTATAACGATCTCACCATCTTCTATTATCA
TTCATAAAGGGTATATCTCGACTTCTGAAGGTCCTCAGAAACATATTTGTTTATCCGGAGATTATTTAAAATACTCTTCAGACAGCGTATTATCTATGGG
ACCCTCACGTCTTTCTATCTGTAATACGCCTGTGTTATTGCTTCCTCAAATCTCCATTATGCCTATGGAGATTCCTAAGCCTCCGATTACTTTTCGAGGT
GGGAGTGGAGGATTTCTGGGATCCTACTTAGGTGTTAGTTATTCCCCTATATCTAAAAAGCATTGTTCTACGACTTTGTTCTTGGATGGTTTTTTTAAAC
ATGGAATAGGTCTCGGCTATAACATGCGCTTTTCCTCTCAGGAAAATCCAAGCAATGCCATAAATATTAAAAGCTATTACGCACATCGATTAGCTATTGA
TTCATCAGGAGCAAAAGATCGCTATCGATTACATGGAGACTTCACTTTTTCCAAAGAACGAGCCCATCTTGCTGGTGAATTCCATTTAAGTGATAGCTGG
GAAACAGTTGTGGATATCTTCCCAAATAACTTCTCTTTAAAAAATACAGGCCCTACAGAAGTTAGCCTATCATGGCGCGATAACAATTTATTTGGGAAAA
TGACTTCCTCTGTCAAAGTCAACTCCTTTCAAAATGTTAAACAAGAATTGCCTCAAGCAATTCTTCATCACCGACCAGTACGTATCAGGCGCTCTCGCAT
TTTCCTAGAGAATCGCTTAGAAGCTGGTTTTTTAGATTTTCATTTCAGTAGTAATATTCCAGGCTCTAACTTCTCATCATGGAGGTTCTCATCCGCTCAC
AAAGTCTACCGTGGGCTTGTTCTTCCTATAGGAACGTTAACCCCTTCGCTATCTGGAACTGCTATCTACTATACCCGCATGCTCTCCCCAAATGCAGCCC
ATTGTCAATTATCTGGATCGCTATCTTTTGATTATCGCGTTGCTTTACAAAAAGAATATCGGCATGCAAGACATATTGTAGAGCCTTTTTGCTCCTTTTT
AAAAACCACTCGTCCTGTATTATCCTCTGATGAGCCTCATATTTTCTCGATTAAAGATGCTTTTCACTCTATCAACCTTCTACATGTAGGATTGGAGTCA
AAAGTCTTAAACAAACATTCCACTCCTTCGCATCTGAAACTATGGACGACCTATATCTTTGATGAACCTCACGCTAAGGACACTTTCCCTAAAACTGCTT
GCTGGTTCTCTCTTCCTCTTACACTCCAAAATACTTTATCCTTAGATGCGGAATGGATTTGGAAAAAAAGCCGATGGGATCATCTCAATGTAATCTGGGA
ATGGATTTTGAATGATAATCTCGGTCTTACTTTAGAATTTTTACATAGAAGTAAGTATGGCTTTATTAAGTGCGCTAAAGATAACTACACACTCGATGTA
AGCCGATCTTTAGACACATTACTAGCCTCTCCTCTTTCCGATCGAAGAAATTTGATTACTGGCAAACTTTTTGTTCGTCCACATCCTCATTGGAATTATA
ATCTTAATCTTCGTTATGGATGGCATCGTCCAGACTCTCCATCCTATTTAGAATACCAGATGATTCTGGGTCATAAAATCTTTGAGCACTGGCAGCTATT
CTCTGTCTACGAAAAACGTGAAGCTGATAAGCGCTGCTTCTTTTATCTAAAATTAGATAAACGAAAACAGAAACACCGCCATCCTTTTGGATAA
SEQ ID 27:
MGLSRLAFISFLSFTLSASCDFPSSVSQRILFSCRKSVPQALEAYLEASATYQQHDFSVLRVIAESYLQQSFLSEDTYIRKSAIIGAGLSGSSEALELLS
EAIETQDLYEQLLILNAATSQLSKTSDKLLFKGLTASHPVIRLEAAYRLACMKNSKVSDYLYSFIYKLPEEIQNLAATIFLQLETEEADAYIHHLLSSPN
NLTRNYVAYLIGEYKQKRFLPTLRSLLTSASPLDQEGALYALGKLEDSGSYPRIKALSSRSNPEVVLAAAQTLLFLEKEEEALPILTNLCQQKLLRALYT
ARFLSQEKGEELLLPIFYNATQEEIRLNTALALVHQGCTDPQVLHYLTEILESKVLHRIFLPTRSTGKAIQFWKECTTFPLMSQEDKMRTLAMYRVAEDT
ILSALLKLPNDAYLPYLERILASQKTILAAKAIAFLSVTAHPQALSLVSKAALTPGDPIIRAYANLALYTMTKDPEKKAVLYRYAEQLIEDTILFTDAEN
PLPSPSSSYLRYQVSPETRTQLMLAILETLVSSKTDEDIRVFLSLMKKTHYKNIPILSGLLMRIVE
SEQ ID 28:
ATGGGACTATCTCGTCTAGCCTTCATTAGTTTCCTCTCTTTTACACTCTCAGCCAGCTGTGATTTTCCTTCCTCAGTTTCTCAGAGAATCTTGTTTTCTT
GCCGAAAATCAGTCCCTCAAGCTCTAGAAGCCTATCTCGAAGCTTCAGCAACTTATCAACAACACGATTTCTCCGTATTACGCGTAATAGCAGAATCGTA
TTTACAACAAAGCTTTCTCTCTGAGGACACCTACATACGTAAAAGTGCAATTATTGGAGCAGGGCTATCTGGTTCATCAGAAGCTTTAGAGTTACTGTCT
GAGGCTATAGAAACGCAAGATCTCTATGAGCAACTACTCATTTTAAATGCTGCAACCAGCCAATTAAGCAAAACTTCTGACAAACTTTTATTCAAGGGAT
TAACAGCTTCTCATCCTGTCATCCGCTTAGAAGCTGCTTATCGTCTTGCCTGTATGAAAAATAGCAAGGTAAGTGATTACCTTTATTCTTTTATCTACAA
GTTACCAGAAGAAATTCAAAACCTAGCGGCAACTATTTTCTTACAACTCGAAACAGAAGAAGCTGATGCTTATATTCATCATTTGCTCTCTTCTCCCAAT
AACCTGACAAGAAACTATGTTGCCTATTTAATTGGAGAGTACAAACAAAAAAGATTTCTTCCAACACTACGCTCTTTACTTACAAGTGCCTCTCCTTTAG
ATCAAGAAGGCGCTTTGTATGCGTTAGGCAAACTGGAAGACTCTGGTAGCTATCCTAGAATTAAAGCTCTAAGCTCTAGATCCAATCCTGAAGTAGTACT
CGCTGCAGCTCAGACATTATTATTCTTAGAGAAAGAAGAAGAAGCTCTACCGATCCTAACCAACCTTTGCCAACAAAAACTTCTTCGAGCCCTGTATACC
GCACGTTTCCTCTCGCAAGAGAAGGGTGAAGAGCTTCTTCTTCCAATCTTTTATAACGCAACACAAGAAGAAATTAGACTGAATACTGCTTTAGCACTTG
TTCATCAAGGGTGTACAGATCCTCAAGTCCTCCACTATCTAACAGAAATCTTAGAAAGTAAAGTTCTCCATCGCATATTTTTACCTACTCACTCGACAGG
AAAAGCTATACAGTTCTGGAAAGAATGCACCACTTTTCCTCTCATGAGCCAAGAAGACAAAATGAGAACGTTGGCTATGTATCGGGTAGCGGAAGATACC
ATCCTCTCAGCGTTACTAAAATTACCCAATGACGCCTATCTTCCTTACCTAGAGCGCATCCTCGCCTCACAAAAAACTATACTAGCAGCTAAAGCTATTG
CTTTTTTATCGGTAACAGCTCATCCTCAGGCACTTTCTTTAGTCTCGAAAGCTGCATTAACTCCTGGAGACCCTATCATTCGCGCTTACGCTAATCTAGC
TTTATATACAATGACCAAAGATCCTGAGAAAAAAGCTGTGCTATACCGATATGCTGAACAATTAATAGAGGATACCATTTTATTCACAGATGCTGAAAAT
CCGCTTCCCTCTCCAAGCTCTTCTTATTTACGCTACCAAGTATCCCCTGAGACCCGCACACAACTTATGCTAGCTATTTTGGAAACCTTAGTTTCTTCCA
AAACGGATGAAGATATCCGCGTTTTTCTTTCCCTAATGAAAAAAACCCATTACAAAAATATCCCGATCTTATCAGGATTGTTAATGAGAATAGTGGAGTG
A
SEQ ID 29:
MREEAMKKQGVLVAPSIMGADLACIGREARNIEESGADLIHIDVMDGHFVPNITFGPGVVAAINRSTELFLEVHAMIYTPFEFVEAFVKAGADRIIVHFE
AAENIKEIISYIQKCGVQAGVAFSPETSIEFVTSFIPLCDVILLMSVHPGFCGQKFIPDTIERIQFVKQAIQVLGREGSCLIEVDGGIDKESARACREAG
ADILVAASYFFEKDSINMKEKVLLLQGEEHGAK
SEQ ID 30:
ATGAGAGAAGAGGCCATGAAAAAACAAGGGGTGTTGGTAGCTCCATCTATTATGGGAGCTGACTTAGCTTGCATAGGAAGAGAAGCGCGAAATATAGAAG
AGTCCGGAGCAGATCTTATTCATATAGACGTTATGGATGGACATTTTGTTCCCAATATTACTTTTGGTCCCGGAGTTGTTGCTGCGATTAATCGGTCAAC
AGAGCTATTTCTGGAAGTTCATGCTATGATTTATACGCCTTTTGAATTTGTAGAGGCTTTTGTTAAGGCCGGGGCGGATCGTATCATTGTGCATTTTGAG
GCAGCGGAAAATATTAAAGAAATTATTAGCTATATTCAAAAATGCGGAGTGCAAGCAGGGGTAGCTTTCTCTCCAGAGACTTCTATAGAGTTTGTCACAT
CTTTCATACCTCTATGCGATGTCATCTTGCTTATGTCTGTGCATCCTGGTTTTTGTGGGCAAAAGTTCATTCCTGATACGATAGAAAGAATTCAATTCGT
TAAACAAGCTATACAAGTCCTAGGAAGAGAAGGAAGTTGCTTGATTGAAGTTGACGGTGGTATTGATAAAGAGTCTGCACGAGCATGTAGGGAAGCAGGC
GCAGATATTTTGGTTGCAGCCTCCTATTTTTTTGAGAAAGACTCTATAAATATGAAAGAAAAAGTTTTGTTACTTCAAGGGGAAGAACATGGTGCTAAGT
AG
SEQ ID 31:
MFVGITYYTTPLLEIALIWVVLNYLLKFFWGTGAMDLVFGLLSFLCLFVLAEKLHLPVIRNLMLHVVNIAAIVVFIIFQPEIRLALSRIRLRRGKFVINM
QDEFIDHLTACIYRMAERQIGALIVLENERLLNDLLNLSAVKINADFSEELLEAIFEPSSHLHDGAVLMRGETISYARVILPLAHDTTQLSRSMGTRHRA
ALGASQRTDALVIVVSEKTGAVSLARDGILTRGVKMDRFKAILRSILTRNERKTNPIISWMRKK
SEQ ID 32:
ATGTTCGTAGGTATAACGTATTACACCACACCTCTGTTGGAGATAGCTTTAATTTGGGTGGTCCTTAATTATTTGCTAAAGTTTTTCTGGGGAACAGGCG
CCATGGACCTCGTCTTTGGCTTGTTGTCTTTTCTTTGCCTATTTGTTCTAGCAGAAAAACTTCATCTCCCCGTTATTCGCAATTTGATGCTTCATGTAGT
GAATATTGCGGCTATCGTGGTATTTATTATCTTCCAACCAGAAATTCGCCTTGCTCTCTCTAGGATACGCTTGCGTAGAGGGAAATTTGTCATCAATATG
CAAGACGAATTCATTGACCATTTGACAGCATGCATCTATCGCATGGCTGAACGACAAATCGGAGCTCTCATTGTATTAGAAAATGAGCGTCTTTTGAATG
ATCTGCTTAATCTCTCTGCCGTGAAAATTAATGCAGATTTTTCAGAAGAACTTCTCGAAGCTATTTTTGAGCCCTCCTCCCATCTACATGATGGAGCCGT
GTTAATGAGAGGCGAGACTATCTCTTACGCTAGAGTAATTCTTCCTCTTGCTCATGATACCACACAACTGTCGCGATCCATGGGAACGCGTCATCGTGCA
GCACTCGGTGCTAGTCAGCGTACCGATGCTCTCGTGATTGTAGTATCAGAAAAGACCGGTGCAGTTTCCTTAGCTCGTGATGGAATTTTAACTCGTGGAG
TAAAGATGGATAGATTTAAAGCCATCCTGCGAAGTATCCTAACGCGCAATGAACGAAAAACAAACCCTATTATCTCCTGGATGCGTAAAAAATGA
SEQ ID 33:
MTSSYMSRLYSLNKSRRILHSSFRLLKSTKMLSHPETQKELQEVLKQLEEAILDQNREDASLFAKQAQAIQKRFPKSKLRATFDLIYALTFAAILAFLIR
QFWFELYEVPTGSMRPTILEQDRILVSKTTFGLRLPFSNKSIGYTPEAITRGELVVFTVGDLPIPSADTKYFGIIPGKKRYIKRCMGKPGDTVYFYGGKI
YGIDCDGEPIFPQNTENLYHVPYISFDGTPEILTHSEEQTDVIFNQFHTPCGKISLPQQASYGQFFYKNAWHNDTPYALKDPHNEPVSYADLFGIKNFAM
VRILTKKQAALTHVLPSPLSDTYLEIAHTPNVSYPHPHLRPFETQLIPTIEPMKTLLPLRKEHIHLIRNNLTTSRFTVVDGYAYKYQPAPMNTSGMARMF
ALPMPNIPDGCYEFSKGDVFKINMSGFRTKLKQPHPLTQLSNSQVIDLFNCGISFHTIYIPKNPQYAPFPNRYAFFHQGNLFVMDSPVFIDSDPALQKFI
VSEEEKELQSSEDKPYIAFIDRGPPPESTEEFVSFITNFGLKIPEGHVLVLGDNCPMSADSRDFGFVPVENLLGSPVGIFWPINRLGLLSSNITPLSLPG
YLVNGLALGAFLYCIGLWYYRKNHRLFP
SEQ ID 34:
ATGACGAGCAGTTACATGAGTCGCTTATATTCCCTGAATAAGAGTCGTCGCATTCTTCATTCTTCCTTTAGATTGCTGAAAAGCACAAAAATGCTCTCTC
ATCCGGAAACTCAAAAAGAACTACAAGAAGTCTTGAAACAGCTTGAAGAGGCTATTTTGGATCAGAATAGGGAAGATGCTTCCCTTTTTGCTAAGCAAGC
TCAAGCCATACAAAAAAGATTCCCTAAATCCAAACTCCGAGCTACTTTTGATCTTATCTATGCTTTGACGTTTGCTGCCATTCTTGCTTTTTTAATCCGC
CAGTTCTGGTTTGAGCTATATGAAGTTCCTACAGGATCTATGCGGCCTACTATTCTTGAACAAGATCGTATTCTTGTTTCCAAAACAACATTTGGACTCC
GGCTACCTTTTAGTAACAAAAGTATTGGCTATACACCTGAGGCTATCACTCGAGGAGAACTGGTAGTCTTCACTGTTGGAGATCTTCCTATCCCTAGCGC
CGACACTAAGTATTTTGGAATCATCCCTGGGAAAAAACGCTATATAAAACGGTGCATGGGTAAACCTGGAGATACCGTATATTTTTATGGAGGGAAAATT
TATGGGATCGATTGCGACGGAGAGCCCATCTTCCCCCAAAATACAGAGAATCTCTACCACGTCCCCTATATTTCTTTTGACGGAACTCCAGAAATCCTTA
CCCATTCAGAAGAGCAAACAGATGTGATCTTTAACCAATTTCACACACCTTGTGGAAAGATTTCTCTCCCTCAACAGGCTTCTTATGGACAATTTTTCTA
TAAGAATGCTTGGCATAATGATACTCCCTATGCTTTAAAAGATCCTCATAATGAGCCTGTTAGCTATGCCGATCTATTCGGAATAAAAAATTTTGCAATG
GTTCGCATCCTTACCAAAAAACAAGCTGCTCTTACTCATGTCCTTCCCTCTCCTCTTTCGGACACCTACCTAGAAATTGCCCACACTCCTAATGTTTCCT
ATCCTCACCCTCACTTACGTCCATTTGAAACACAGCTTATTCCTACTATCGAACCTATGAAAACCTTGCTTCCTTTAAGGAAGGAACATATTCATTTGAT
TCGTAATAACCTCACAACATCCCGTTTTACAGTTGTAGATGGATATGCTTACAAGTACCAACCTGCTCCCATGAATACCTCAGGCATGGCCAGGATGTTT
GCCCTACCTATGCCAAATATTCCTGACGGATGTTATGAATTTTCTAAAGGAGACGTGTTTAAAATTAATATGAGTGGCTTTCGAACGAAACTCAAACAGC
CGCATCCTTTAACGCAATTAAGCAATTCTCAGGTCATTGACTTATTTAATTGCGGCATTAGTTTCCACACGATCTATATTCCTAAAAACCCTCAATATGC
TCCGTTCCCTAATCGCTATGCATTTTTCCATCAAGGGAACCTGTTCGTTATGGATTCTCCAGTTTTTATTGATAGCGATCCTGCCTTACAGAAATTCATT
GTGTCTGAAGAGGAAAAAGAACTTCAATCATCTGAAGACAAACCTTACATCGCGTTTATTGACAGAGGTCCTCCTCCAGAATCTACAGAGGAATTTGTTT
CCTTTATTACTAATTTCGGTCTTAAAATTCCGGAAGGCCACGTGCTTGTCTTAGGAGATAATTGTCCTATGAGCGCTGATAGCCGTGATTTTGGTTTTGT
TCCCGTTGAAAATCTTTTGGGATCTCCTGTTGGGATCTTCTGGCCTATTAATCGTCTAGGATTGTTATCTTCCAATATAACGCCCTTGAGTTTACCTGGC
TACCTCGTAAATGGATTGGCTCTAGGAGCTTTTCTTTACTGCATAGGATTATGGTACTATCGAAAAAACCATAGGCTATTCCCTTAA
SEQ ID 35:
MFKLIKSAFLIACCIVGYFWIKKESIVEQWLSQQLHAQVTVGNISPGLSKTKIRHLCIHNPLSSDKYPYAVEIEYVSLKYSIVTMILSKKIDISDVILQG
TSLTVFPCEGSSKTNWSFFWDSFINHSNELTKFHSSQFESSVDTIPVFIKRCLCTNTRVSGIKNNYKEIPTTPVPSLEFRGSLSCSPLPTLGETARALLY
LIVEESFYHANVSGDIARPLSKQARAYFNSSLSDYSYLKKRGTFPSNLTNELEGFMKELLFR
SEQ ID 36:
ATGTTTAAACTAATCAAGAGCGCATTTCTCATAGCCTGTTGTATTGTAGGGTACTTCTGGATAAAAAAAGAAAGTATTGTTGAGCAGTGGCTATCCCAAC
AGTTGCATGCTCAAGTGACCGTTGGCAATATTTCCCCCGGTCTTTCCAAAACGAAGATTCGCCATTTATGTATCCACAATCCTCTTTCTTCCGATAAGTA
TCCCTATGCGGTAGAAATTGAGTACGTGAGTCTCAAGTACTCTATTGTTACCATGATTCTTTCGAAAAAGATCGATATTTCTGATGTAATCCTACAAGGA
ACATCTCTAACTGTATTCCCCTGCGAAGGATCTTCTAAGACAAACTGGTCATTCTTTTGGGATAGCTTTATCAATCATTCTAATGAGCTGACCAAGTTTC
ATTCTTCACAGTTTGAGTCATCTGTTGATACAATCCCCGTATTCATTAAACGTTGTCTATGTACAAACACGAGAGTCAGTGGCATCAAAAACAACTATAA
GGAAATCCCTACTACACCTGTGCCGTCTCTCGAATTTAGAGGGTCTTTATCTTGTTCTCCTCTACCAACTTTAGGAGAAACTGCGAGAGCCTTACTGTAT
CTCATCGTGGAAGAGAGTTTTTATCACGCAAATGTTTCGGGAGATATCGCTCGTCCTCTTTCTAAACAGGCTCGAGCATACTTCAATTCTTCTCTATCCG
ATTACTCTTATCTAAAAAAACGAGGAACATTTCCTTCGAATCTTACCAATGAACTTGAGGGTTTTATGAAAGAGTTGCTATTCCGATAG
SEQ ID 37:
MNVSDLLNILNELLHPEYFSDYGPNGLQVGNAQTAIRKVAVAVTADLATIEKAIACEANVLLVHHGIFWKGMPYSITGILYQRMQRLMEGNIQLIAYHLP
LDAHTTIGNNWKVARDLGWEQLESFGSSQPSLGVKGVFPEMEVHDFISQLSAYYQTPVLAKALGGKKRVSSAALISGGAYREISEAKNQQNDCFITGNFD
EPAWSLAHELAIHFLAFGHTATEKVGPKALAQYLKGAGLESVVFLDTDNPF
SEQ ID 38:
ATGAACGTTTCAGACCTTCTCAATATTTTGAATGAACTGTTACATCCTGAATATTTTAGTGACTATGGCCCTAATGGTTTACAAGTTGGTAATGCACAAA
CTGCGATTCGTAAGGTGGCGGTTGCAGTCACAGCGGATTTAGCAACTATTGAGAAGGCAATAGCTTGCGAAGCCAATGTTTTGCTTGTACATCACGGGAT
ATTTTGGAAGGGGATGCCCTATTCCATCACAGGGATACTCTATCAGCGTATGCAACGCTTGATGGAAGGGAATATTCAGTTGATAGCTTATCATTTACCG
TTAGACGCGCATACAACGATTGGTAATAACTGGAAAGTAGCAAGGGATCTAGGTTGGGAACAACTAGAATCTTTCGGAAGCTCTCAGCCTTCTTTAGGAG
TTAAGGGAGTCTTCCCAGAAATGGAGGTTCATGATTTCATATCTCAATTATCTGCATACTATCAAACACCGGTATTAGCGAAAGCTCTTGGAGGAAAGAA
AAGAGTTTCTTCTGCAGCGCTTATTTCTGGCGGGGCTTATCGTGAAATTTCCGAAGCTAAAAACCAGCAGGTAGACTGCTTCATCACTGGTAATTTTGAT
GAGCCGGCATGGTCTTTAGCGCATGAGCTGGCTATTCATTTTTTGGCTTTTGGACATACAGCTACTGAAAAAGTTGGTCCAAAAGCCTTGGCTCAATATT
TAAAAGGAGCGGGTTTAGAATCAGTTGTGTTTTTGGATACGGACAACCCTTTTTAA
SEQ ID 39:
MKKFATFLCVLLSGSGFAAPVEVPGFPSIPETYITINDKELGLQEHCRGVNVLSCGYNLVGMFHTPTTPMPLGGYPTVIFFHGFRGNCTGKDGVYRDLAR
LLTANGIAVARFDMAGCGNSEGICDQIPARTYLRNGEDILATVAKYPEVNPHRIGIAGISLGCHTTIHLASTYRPRDYTVQAISVWAPIADGVILLKEIC
ATIGLTMTQFSDMGEVGKAFGFKQLPLKLCRDDIDFFLGIQDHILLLSLPRRIPVLHQQGLEDHVVSTAHQRLFLGAAPAQMLSKSYPETPHEIASSPYR
QEVLQEILTHFQSNL
SEQ ID 40:
ATGAAAAAGTTTGCTACTTTCCTGTGTGTACTCTTATCTGGAAGTGGTTTTGCAGCTCCTGTTGAAGTGCCTGGGTTTCCCTCTATTCCTGAAACCTACA
TTACTATCAATGATAAGGAATTAGGTCTTCAAGAGCATTGCCGTGGTGTTAATGTTCTCAGCTGCGGATATAATTTAGTTGGTATGTTCCATACCCCAAC
CACTCCTATGCCTCTAGGAGGATATCCTACTGTAATCTTTTTCCATGGATTCCGCGGAAATTGTACAGGAAAGGATGGGGTCTATCGAGACTTAGCCCGC
CTTCTTACGGCAAATGGAATCGCTGTAGCCAGATTCGATATGGCTGGCTGTGGAAATAGCGAAGGAATATGTGATCAAATCCCTGCACGAACCTACCTGC
GCAACGGCGAAGATATCTTAGCCACCGTAGCTAAATACCCAGAAGTCAACCCTCACCGCATTGGTATTGCAGGAATTTCCTTAGGTTGTCACACTACCAT
TCATCTGGCTAGCACCTATAGACCTAGAGACTATACGGTTCAAGCCATCTCCGTCTGGGCTCCTATTGCTGACGGAGTCATCCTTCTCAAAGAGATCTGT
GCTACTATTGGCCTAACCATGACCCAGTTTTCGGATATGGGTGAAGTGGGTAAAGCATTTGGATTCAAACAACTTCCCCTCAAGCTGTGTCGAGATGATA
TCGATTTCTTCTTAGGTATTCAGGATCACATCCTCCTGCTATCCTTACCAAGAAGAATCCCCGTTCTCCACCAACAAGGACTAGAAGATCACGTAGTTTC
TACGGCTCACCAACGCCTATTTTTAGGGGCTGCTCCAGCGCAAATGCTGTCTAAGAGTTACCCCGAAACTCCCCATGAAATCGCTTCATCTCCTTATCGC
CAAGAGGTTTTGCAGGAAATCTTAACGCATTTCCAATCAAATCTTTAA
SEQ ID 41:
MRFLLALFSLILVLPATEAFSTEDKQCQQEAEEDCSQVADTCVFYSYAEGLEHARDEGKLTLVVLLDTSGYSFETLADAAHAMESSLLSTFADFVVLSRR
EAVPLIYPPVPDPMVGEIALFLEAFSDQTFPSQPVIVTLAIGASSAEIMDITEIPSINPEFVE
SEQ ID 42:
ATGAGATTCTTGTTAGCTTTATTCTCACTGATACTAGTTCTTCCTGCGACTGAGGCATTCTCAACAGAGGATAAGCAGTGTCAACAAGAAGCAGAGGAAG
ACTGTAGTCAGGTAGCGGACACCTGCGTATTTTATAGCTATGCAGAGGGTTTAGAACACGCAAGGGACGAAGGGAAACTCACCTTAGTAGTATTGTTAGA
TACTTCTGGGTATTCCTTCGAGACTCTTGCTGATGCAGCCCATGCTATGGAAAGTTCGTTGCTATCCACATTTGCTGATTTTGTGGTTCTTTCTAGGAGG
GAAGCAGTTCCACTGATTTATCCTCCGGTTCCAGATCCTATGGTTGGCGAGATAGCGTTGTTCTTAGAAGCTTTCTCAGATCAAACATTTCCATCACAGC
CTGTGATTGTTACCTTAGCTATTGGGGCTTCTTCTGCAGAGATCATGGATATTACCGAGATTCCGTCAATAAATCCTGAATTTGTTGAGTAG
SEQ ID 43:
MRKISVGICLLLALATSGCSKSSSNATHRSPATHTVAVSVKDDPRTFDPREVRLLSDLNLIHHLYEGLVQETPSGEVFPALAESFFLSEDKKTYTFNLKK
AFWSNGDLITAHDFVRSWNDVLQNRVASIYSFAFLPIDVNKDSGFFAKDDHTLVINLLTPTPHFLKLLTLPVFYPVHSQHQIRKEEKSLPISTGAFFLKE
KKDRRWLKLEKSPYYYNKDQVAVQEICIHIIPDQQTASALFNQGKLDWQGLPWGHSIPQETLATTNKRRAPRSFDISGTSWLTFNTAKKPFSHSKLRQAL
SLVLNKEALASLAFVKPAKHLLPAHLHTYPEQPSYKQQEAITLAKSLLEEALTELNMTIEDLEKYPLTFSATSTMNSQIAQMLRDQWRRSLGITFPICGK
EYALLQNDLIGNTFFMSIGGWFADFSDPLAFLSIFSSKGVKPYALQDPQFDQLILSIETEKNPQKRSALISEASLYIERQNVIEPLYHDVFHYTTNNKLS
FVRLHPSGLVDMRYAKNS
SEQ ID 44:
ATGCGCAAGATATCAGTGGGAATCTGCTTGCTCCTAGCATTAGCAACTTCTGGATGTTCAAAATCCTCCTCTAACGCAACCCATCGGTCTCCAGCTACTC
ACACAGTTGCTGTAAGCGTAAAAGATGATCCTCGCACATTTGATCCTCGAGAGGTTCGCCTTCTTTCTGATATCAATTTGATTCATCATCTCTATGAAGG
ATTGGTACAAGAAACTCCTTCTGGAGAAGTCTTCCCTGCTTTAGCGGAGAGTTTCTTCTTATCCGAAGATAAAAAAACTTATACTTTCAACTTGAAAAAA
GCTTTTTGGAGCAATGGAGATCTTATTACCGCTCATGATTTTGTTCGTTCCTGGAATGATGTGTTACAAAATCGTGTCGCTAGTATTTATTCTTTCGCCT
TTCTCCCTATTGACGTGAATAAGGATTCTGGATTTTTTGCCAAAGATGATCATACTCTTGTTATCAATCTCCTCACTCCAACTCCACATTTTCTAAAGCT
GCTTACCCTCCCCGTATTTTATCCTGTGCATTCGCAGCATCAGATACGGAAAGAAGAAAAATCTCTTCCGATATCTACTGGAGCTTTTTTCTTAAAAGAG
AAGAAAGACCGAAGATGGTTAAAGCTAGAGAAGAGCCCTTACTACTATAATAAAGACCAGGTAGCTGTACAGGAGATCTGTATACACATCATTCCTGATC
AACAAACTGCTTCTGCTTTATTCAACCAAGGGAAGCTAGATTGGCAAGGTCTCCCTTGGGGACATAGTATTCCGCAAGAAACTTTAGCCACAACAAACAA
ACGACGAGCTCCCCGATCATTTGATATATCTGGTACTTCCTGGCTTACATTTAACACTGCCAAAAAGCCTTTTAGTCATTCCAAGCTTCGCCAAGCTTTG
AGTCTAGTTTTAAACAAAGAAGCTCTTGCCTCCTTGGCTTTTGTTAAACCTGCAAAACATCTCCTTCCTGCACATTTGCACACCTACCCAGAGCAGCCTT
CTTATAAGCAACAAGAGGCCATCACTTTAGCTAAATCTTTACTAGAAGAAGCTCTGACTGAGCTTAACATGACTATTGAGGATCTAGAGAAGTATCCTCT
TACCTTTTCCGCAACGTCTACTATGAACTCACAGATAGCTCAGATGTTGCGCGATCAGTGGCGAAGAAGTTTAGGAATTACTTTCCCTATCTGCGGGAAA
GAATATGCTTTGTTGCAAAACGATCTAATAGGCAATACTTTCTTTATGTCTATAGGTGGCTGGTTTGCCGACTTTTCTGACCCTTTAGCGTTTCTTTCCA
TTTTCTCCTCGAAAGGAGTCAAACCTTATGCTTTACAAGATCCTCAATTTGATCAACTGATTCTCTCTATAGAAACGGAAAAAAACCCTCAAAAACGCTC
AGCTTTAATTTCCGAAGCTTCTCTATACATAGAAAGACAAAACGTCATAGAACCCCTCTATCACGACGTGTTCCATTATACAACAAATAATAAACTTTCT
TTTGTTAGACTACATCCTTCGGGCCTAGTTGATATGCGGTATGCTAAAAACTCTTAA
SEQ ID 45:
MRKISVGICLLLALATSGCSKSSSNATHRSPATHTVAVSVKDDPRTFDPREVRLLSDINLIHHLYEGLVQETPSGEVFPALAESFFLSEDKKTYTFNLKK
AFWSNGDLITAHDFVRSWNDVLQNRVASIYSFAFLPIDVNKDSGFFAKDDHTLVINLLTPTPHFLKLLTLPVFYPVHSQHQIRKEEKSLPISTGAFFLKE
KKDRRWLKLEKSPYYYNKDQVAVQEICIHIIPDQQTASALFNQGKLDWQGLPWGHSIPQETLATTNKRRAPRSFDISGTSWLTFNTAKKPFSHSKLRQAL
SLVLNKEALASLAFVKPAKHLLPAHLHTYPEQPSYKQQEAITLAKSLLEEALTELNMTIEDLEKYPLTFSATSTMNSQIAQMLRDQWRRSLGITFPICGK
EYALLQNDLIGNTFFMSIGGWFADFSDPLAFLSIFSSKGVKPYALQDPQFDQLILSIETEKNPQKRSALISEASLYIERQNVIEPLYHDVFHYTTNNKLS
FVRLHPSGLVDMRYAKNS
SEQ ID 46:
ATGCGCAAGATATCAGTGGGAATCTGCTTGCTCCTAGCATTAGCAACTTCTGGATGTTCAAAATCCTCCTCTAACGCAACCCATCGGTCTCCAGCTACTC
ACACAGTTGCTGTAAGCGTAAAAGATGATCCTCGCACATTTGATCCTCGAGAGGTTCGCCTTCTTTCTGATATCAATTTGATTCATCATCTCTATGAAGG
ATTGGTACAAGAAACTCCTTCTGGAGAAGTCTTCCCTGCTTTAGCGGAGAGTTTCTTCTTATCCGAAGATAAAAAAACTTATACTTTCAACTTGAAAAAA
GCTTTTTGGAGCAATGGAGATCTTATTACCGCTCATGATTTTGTTCGTTCCTGGAATGATGTGTTACAAAATCGTGTCGCTAGTATTTATTCTTTCGCCT
TTCTCCCTATTGACGTGAATAAGGATTCTGGATTTTTTGCCAAAGATGATCATACTCTTGTTATCAATCTCCTCACTCCAACTCCACATTTTCTAAAGCT
GCTTACCCTCCCCGTATTTTATCCTGTGCATTCGCAGCATCAGATACGGAAAGAAGAAAAATCTCTTCCGATATCTACTGGAGCTTTTTTCTTAAAAGAG
AAGAAAGACCGAAGATGGTTAAAGCTAGAGAAGAGCCCTTACTACTATAATAAAGACCAGGTAGCTGTACAGGAGATCTGTATACACATCATTCCTGATC
AACAAACTGCTTCTGCTTTATTCAACCAAGGGAAGCTAGATTGGCAAGGTCTCCCTTGGGGACATAGTATTCCGCAAGAAACTTTAGCCACAACAAACAA
ACGACGAGCTCCCCGATCATTTGATATATCTGGTACTTCCTGGCTTACATTTAACACTGCCAAAAAGCCTTTTAGTCATTCCAAGCTTCGCCAAGCTTTG
AGTCTAGTTTTAAACAAAGAAGCTCTTGCCTCCTTGGCTTTTGTTAAACCTGCAAAACATCTCCTTCCTGCACATTTGCACACCTACCCAGAGCAGCCTT
CTTATAAGCAACAAGAGGCCATCACTTTAGCTAAATCTTTACTAGAAGAAGCTCTGACTGAGCTTAACATGACTATTGAGGATCTAGAGAAGTATCCTCT
TACCTTTTCCGCAACGTCTACTATGAACTCACAGATAGCTCAGATGTTGCGCGATCAGTGGCGAAGAAGTTTAGGAATTACTTTCCCTATCTGCGGGAAA
GAATATGCTTTGTTGCAAAACGATCTAATAGGCAATACTTTCTTTATGTCTATAGGTGGCTGGTTTGCCGACTTTTCTGACCCTTTAGCGTTTCTTTCCA
TTTTCTCCTCGAAAGGAGTCAAACCTTATGCTTTACAAGATCCTCAATTTGATCAACTGATTCTCTCTATAGAAACGGAAAAAAACCCTCAAAAACGCTC
AGCTTTAATTTCCGAAGCTTCTCTATACATAGAAAGACAAAACGTCATAGAACCCCTCTATCACGACGTGTTCCATTATACAACAAATAATAAACTTTCT
TTTGTTAGACTACATCCTTCGGGCCTAGTTGATATGCGGTATGCTAAAAACTCTTAA
SEQ ID 47:
MYVRSIFFSIIAFLTVGCSFSPPESGLIIAIHDDPRSLSPEKGENAFHFSLSKALFATLFREELSGLTPALVSSYQVSEDGRFYRFCIRKDAKWSDGSLL
LAEDVIAAWEHTKQAGRYSLLFEKLSFRASSSSEILIELKEPEPQLLAILASPFFAVYRPENPFLSSGPFMPKTYVQGQTLVLQKNPYYYDHAHVELHSI
DFRIIPNIYTALHLLRRGDVDWVGQPWHQGIPFELRTTSALYTHYSVDGTFWLILNPKDPVLSSLSNRQRLIAAVQKEKLVKQALGTQYRVAESSPSPEG
IIAHQEASTPFPGKITLIYPNNITRCQRLAEVLQEQCRDAGIQLTLEGLEYHVFVQKRATQDFSVSTATSIAFHPLAKSKFDQTALDNFTCLPLYHIEYD
YILSRPLDQIVHYPSGSVDLTYAHFH
SEQ ID 48:
ATGTATGTTCGCTCTATCTTTTTTAGTATTATCGCCTTCCTAACGGTCGGATGCTCCTTTTCTCCTCCAGAATCGGGCTTAATCATAGCCATTCACGATG
ATCCTCGCTCTCTTTCTCCAGAAAAAGGAGAAAATGCTTTCCATTTTTCTTTGTCCAAGGCTTTATTTGCTACTCTCTTCAGAGAAGAGCTCTCTGGATT
AACCCCTGCTCTGGTCTCCTCCTATCAAGTTTCGGAAGACGGGCGGTTTTATCGTTTTTGTATTCGTAAAGATGCTAAGTGGAGTGACGGCTCTCTTTTA
CTTGCAGAAGATGTAATAGCTGCTTGGGAACACACTAAACAAGCTGGGCGATATTCCCTACTTTTTGAAAAGCTATCTTTTCGAGCCTCTTCTTCTTCAG
AAATCCTTATTGAACTCAAAGAACCCGAGCCTCAACTATTGGCGATATTAGCCTCTCCGTTTTTTGCTGTGTATCGTCCAGAAAATCCTTTTCTTTCTTC
TGGACCTTTTATGCCAAAAACCTATGTGCAAGGGCAAACGCTCGTTCTACAAAAAAACCCTTATTACTATGACCATGCGCATGTGGAATTACATTCCATA
GACTTTCGCATCATTCCCAACATTTACACAGCTCTACACCTCTTAAGAAGAGGTGACGTGGATTGGGTGGGGCAGCCTTGGCACCAAGGGATTCCTTTTG
AGCTTCGGACTACCTCTGCTCTCTACACCCATTACTCTGTAGATGGCACATTCTGGCTTATTCTTAATCCCAAAGATCCTGTACTTTCCTCTCTATCTAA
TCGTCAGCGATTGATTGCTGCCGTCCAAAAGGAAAAACTGGTGAAGCAAGCTTTAGGAACACAATATCGAGTAGCTGAAAGCTCTCCATCTCCAGAGGGA
ATCATAGCTCATCAAGAAGCTTCTACTCCTTTTCCTGGGAAAATTACTTTGATATATCCCAATAATATTACGCGCTGTCAGCGTTTGGCCGAGGTATTGC
AAGAACAATGCCGAGACGCAGGTATCCAGCTGACTCTTGAAGGACTCGAATACCATGTATTTGTTCAAAAACGAGCCACTCAAGATTTCTCTGTCTCCAC
AGCAACTTCTATAGCTTTCCATCCCCTTGCTAAATCTAAGTTCGATCAAACGGCTCTAGACAATTTCACTTGTCTGCCCTTGTACCACATAGAATATGAT
TATATTTTGAGCAGACCGCTAGATCAAATTGTTCACTATCCTTCAGGTAGTGTTGATTTGACCTATGCACACTTTCACTAG
SEQ ID 49:
MHHRKFLAVSIAFVSLAFGLTSCYHKKEEPKDVLRIAICHDPMSLDPRQVFLSKDVSIVKALYEGLVREKEAAFQLALAERYHQSDDGCVYTFFLKNTFW
SNGDVVTAYDFEESIKQIYFREIDNPSLRSLALIKNSHAVLTGALPVEDLGVRALNAKTLEIVLENPFPYFLEILAHPVFYPVRTSLREYYKDKRNKRVF
PIISNGPFAIQCYEPQRYLLINKNPLYHAKHDVLLNSVCLQIVPDIHTAMQLFQKNHIDLVGLPWSSSFSLEEQRNLPREKLFDYPVLSCSVLKCNIHQT
PLNNPSLRTALSLAINRETLLKLAGKGCSATSFVHPQLSQIPATTLSQDERIALAKGYLTEALKTLSQEDLEKITLIYPIESVCLRAVVQEIRQQLFDVL
GFKISTLGLEYHCFLDKRSRGEFSLATGNWIADYHQASAFLSVLGNGTRYKDFQLINWQNQKYTNIVAQLLIQESSDLQLMAEQLLLKESPLIPLYHLDY
VYAKQPRVSDLQTSSRGEIDLKRVSLAEG
SEQ ID 50:
ATGCATCACAGGAAGTTTTTAGCAGTTTCCATTGCTTTCGTAAGTTTAGCTTTTGGGCTAACATCTTGTTATCATAAAAAAGAAGAACCAAAAGATGTTT
TGCGGATTGCGATCTGTCATGATCCAATGTCTTTAGATCCGCGTCAGGTTTTTTTAAGCAAAGATGTTTCTATTGTAAAAGCTCTCTATGAAGGGTTAGT
CCGGGAAAAAGAAGCTGCGTTCCAGCTAGCTTTGGCAGAAAGATATCATCAATCTGATGATGGTTGTGTTTATACTTTTTTTCTAAAAAATACATTCTGG
AGCAACGGAGATGTTGTAACAGCATATGATTTTGAAGAGTCTATTAAACAAATTTATTTCCGAGAAATTGATAACCCTTCGTTACGCTCTCTTGCATTAA
TTAAAAATTCTCATGCTGTTTTAACAGGAGCTCTCCCTGTTGAAGATTTAGGTGTTAGAGCTTTGAATGCGAAAACTCTAGAAATTGTTTTAGAAAACCC
GTTTCCTTATTTTCTAGAGATATTGGCGCACCCGGTTTTTTATCCGGTGCACACCTCTTTACGAGAATATTACAAAGATAAGCGTAACAAACGCGTTTTC
CCGATAATTTCTAATGGTCCTTTTGCGATTCAATGTTATGAGCCGCAAAGATATTTACTAATCAACAAAAACCCTCTGTATCATGCCAAGCACGATGTTC
TGTTAAATTCGGTATGTTTGCAGATAGTTCCTGATATCCATACAGCTATGCAGTTATTCCAAAAAAATCATATCGATTTAGTTGGGTTACCCTGGAGCTC
CTCCTTTTCTTTAGAAGAACAAAGAAATCTCCCTAGAGAAAAATTATTTGATTATCCTGTATTGAGTTGCTCTGTTTTATTCTGTAACATTCATCAAACA
CCTTTAAATAATCCCTCGCTGAGAACAGCCCTCTCTTTAGCAATCAATCGAGAAACTTTATTAAAACTAGCAGGTAAAGGCTGTAGCGCTACGAGCTTTG
TTCACCCACAATTATCTCAGATACCTGCTACTACTTTGTCTCAAGATGAGCGGATTGCTTTAGCAAAAGGCTACTTGACCGAAGCTTTAAAGACTTTATC
TCAAGAAGATTTAGAAAAAATTACATTAATTTATCCTATAGAATCTGTTTGCTTACGAGCCGTTGTTCAAGAAATTCGCCAACAATTATTTGATGTACTG
GGATTTAAAATTTCTACATTAGGATTAGAATATCATTGTTTTTTAGACAAACGTTCCAGAGGAGAATTCTCCTTAGCAACTGGTAATTGGATTGCAGACT
ATCATCAAGCTAGTGCTTTCCTGTCTGTCCTAGGTAATGGGACAAGATATAAAGACTTTCAATTGATTAACTGGCAGAACCAAAAGTACACAAATATAGT
TGCTCAACTTCTGATTCAAGAATCAAGCGACCTACAGCTTATGGCAGAGCAGTTGTTGCTTAAAGAAAGTCCTCTTATTCCTCTATACCACCTCGATTAT
GTGTATGCGAAACAGCCTCGGGTGTCTGATCTCCAAACCTCTTCTCGTGGAGAAATTGATTTAAAAAGAGTTTCATTAGCTGAAGGATAG
SEQ ID 51:
MPHQVLLSPVCDLLSNAEGIETQVLFGERICNHNHRHYAYSQLVFSSIWKPYPGDSLQNIPLFSSQLQPPNAVVCSQEAFLDPWHIPLPFAAPLHIDNQN
QVSLSPASIALLNSNSRSNYAKAFCSTKEIRFLNSSFSPRDLVSFAEQLIDTPYVWGGRCIHKQLPRNGVDCSGYIQLLYQVTGRNIPRNARDQYRDCSP
VKDFSSLPIGGLIFLKKASTGQINHVMMKISEHEFIHAAEKIGKVEKVILGNRAFFKGNLFCSLGEPPIEAVFGVPKNRKAFF
SEQ ID 52:
ATGCCGCACCAAGTCTTATTGTCTCCTGTTTGCGATCTTTTATCGAATGCTGAAGGTATAGAGACGCAAGTACTGTTTGGAGAAAGGATATGCAACCATA
ACCATCGACACTATGCCTATTCTCAACTAGTCTTTTCTTCTATATGGAAGCCATACCCTGGCGACTCTCTACAGAATATTCCTCTATTCTCTTCCCAACT
GCAGCCTCCTAATGCTGTTGTCTGCTCTCAAGAAGCTTTTTTAGATCCTTGGCATATCCCCTTACCTTTTGCCGCTCCGCTCCACATAGATAACCAAAAT
CAAGTGTCCCTATCTCCTGCTAGCATAGCATTATTAAATTCCAATTCCAGAAGTAACTATGCAAAAGCTTTCTGCTCTACCAAAGAGATTCGTTTTTTAA
ATTCTTCATTCTCTCCAAGAGATTTAGTTTCTTTCGCAGAACAATTGATAGATACTCCGTACGTTTGGGGTGGCCGGTGCATTCATAAACAGCTTCCTCG
TAATGGTGTAGATTGTTCGGGGTATATTCAACTACTTTACCAAGTCACAGGAAGAAATATCCCTCGCAATGCTAGAGATCAATACAGAGACTGTTCTCCA
GTAAAAGATTTCTCGTCTCTACCTATAGGAGGACTTATCTTCCTCAAGAAAGCAAGCACGGGACAAATCAACCATGTTATGATGAAAATCTCGGAGCATG
AATTCATTCATGCTGCGGAAAAAATAGGGAAAGTAGAAAAAGTAATCCTAGGAAATAGGGCTTTCTTTAAAGGGAATCTATTCTGCTCATTAGGTGAACC
GCCTATAGAAGCTGTTTTTGGCGTTCCTAAAAATAGAAAAGCCTTCTTTTGA
SEQ ID 53:
MTYSISDIAHKSDISNPTSPAPSRKRGSFPPQSPSAVGSLEGANFSTWGPGPFFTVPVYPQQLAAMQNNLFTLQTEVSALKKKLVQSSQTRGSLGLGPQF
LAACLVAATILAVAVIVLASLGLGGVLPFVLVCLAGSTNAIWAIVSASITTLICCVSIACIFLAKCDKGSDPQTLYVS
SEQ ID 54:
ATGACGTACTCTATATCCGATATAGCACACAAATCTGATATTTCTAATCCCACGTCTCCCGCTCCATCAAGAAAACGAGGATCCTTTCCCCCACAATCTC
CTTCTGCCGTGGGCTCTTTAGAGGGAGCTAATTTCTCTACATGGGGGCCAGGCCCCTTCTTCACTGTCCCTGTTTATCCACAACAACTCGCTGCAATGCA
AAACAACCTTTTTACATTGCAAACAGAGGTTTCTGCTCTCAAGAAAAAATTAGTTCAGTCTAGTCAGACACGCGGATCTTTAGGACTCGGCCCGCAGTTT
TTAGCGGCATGCTTAGTTGCTGCGACAATCCTTGCAGTAGCTGTTATCGTACTTGCTTCCTTAGGACTTGGCGGTGTTCTTCCTTTTGTCCTTGTTTGTC
TGGCTGGGTCAACTAATGCAATTTGGGCTATTGTGAGCGCCTCCATCACTACACTGATTTGTTGCGTTTCCATCGCTTGCATCTTCTTAGCAAAATGTGA
TAAGGGATCTGATCCTCAAACTTTATATGTAAGCTAA
SEQ ID 55:
MLGIRKKTILQLAVLLLLTFSRSSFCSTSEGRMVVESITITTQGENTQNKRAIPKIKTKQGTLFSQADFDEDLRTLSKDFDRVEPIVEFRNGQAVISLIL
TAKPVIREINISGNEAIPTHKILKTLELYKNDLFDRELFFKNFDALRTLYLKRGYYDSQLSYSHNHNEKEGFIDISIEIKEGRHGRIKKLTISGITRTEA
SDLGDIVLTKQYSTTTSWFTGAGVYHPDMVEQDLFAITNYFQNKGYADAKVSKEVSTDAKGNITLLIVVDKGPLYTLGHVHIEGFTALSKRLLDKQLLVG
PNSLYCPDKIWTGAQKIRSAYARYGYVNTNVDVSFSAHPTLPVYDVTYRVSEGSPYKIGLIKIKGNTHTKHDVILHETSLFPGDTFDRLKLEGTETRLRN
TGYFKSVSVYTVRSQLDPLDSNDLYRDVFIEVKETETGNLGLFLGFSSIDHLFGGAEIAESNFDLFGARNFLKKGFKSLRGGGEYLFLKANLGDKVTDYT
VKWTKPHFLNTPWILGVELDKSINKALSKDYSVDTYGGNISTTYILNDKLKYGMYYRGSQTSLSLRKKTSSSNRPGPDLDSNKGFVSAAGLNVLYDSIDN
PRKPTMGIRSSLNFELSGLGGTYQFTKLTASGSIYRLLTKKGVLKVRAEAKFIKPFGTTTAQGIPVSERFFLGGETTVRGYKPFIIGPKFSPTEPQGGLS
SLLLTEEFQYPLISQPCINAFVFLDSGFIGIEEYTIRLKDLCSSAGFGLRFDMMNNVPIMLGWGWPFRPTEILNNEKIDVSQRFFFALGGVF
SEQ ID 56:
ATGCTTGGAATACGCAAAAAAACGATTCTGCAACTCGCTGTTTTACTGTTGCTCACCTTTTCACGAAGTTCTTTCTGTTCAACTTCAGAAGGACGTATGG
TCGTAGAGTCTATCACCATTACGACTCAAGGAGAGAATACTCAAAATAAACGAGCTATTCCTAAAATAAAAACAAAGCAGGGGACGTTGTTCTCTCAAGC
AGATTTTGATGAAGATCTAAGAACACTTTCGAAAGATTTTGATCGAGTAGAGCCTATCGTAGAGTTTCGTAATGGACAAGCTGTGATCTCTCTGATTCTG
ACGGCAAAACCTGTTATCAGAGAGATCAATATTTCAGGAAATGAAGCTATCCCCACTCATAAAATTCTGAAAACTTTAGAGCTTTATAAAAATGATCTTT
TTGATCGGGAATTATTCTTTAAAAATTTTGATGCGCTAAGAACTCTTTATTTGAAACGAGGGTACTACGATTCTCAACTCTCCTATTCTCATAATCATAA
TGAGAAAGAGGGCTTTATCGATATTTCCATCGAGATTAAAGAAGGACGTCACGGTCGCATAAAAAAATTAACGATTTCGGGAATTACGCGAACAGAAGCA
TCAGACTTAGGTGACATTGTTTTAACTAAACAATACTCCACAACAACGAGCTGGTTCACTGGTGCCGGAGTGTATCATCCGGACATGGTAGAGCAAGACT
TATTTGCTATCACAAATTACTTCCAAAATAAAGGATATGCTGATGCTAAAGTAAGCAAAGAGGTCTCTACAGATGCTAAAGGAAACATTACTTTGCTTAT
CGTTGTAGACAAAGGACCTTTATACACATTAGGTCACGTACATATAGAAGGATTCACAGCGTTATCCAAAAGACTGCTCGATAAACAACTATTGGTTGGA
CCTAACTCCTTATATTGCCCAGATAAAATTTGGACTGGAGCACAAAAGATTCGTAGCGCATACGCTAGATATGGCTACGTGAACACTAACGTTGATGTCT
CCTTCTCAGCGCACCCCACTCTACCTGTTTACGATGTTACCTATCGAGTGAGTGAAGGATCTCCCTACAAAATCGGGTTAATTAAAATCAAAGGGAACAC
TCATACTAAGCATGATGTGATTTTGCATGAGACTAGTCTTTTCCCTGGAGACACTTTTGATAGATTAAAACTGGAAGGTACAGAGACTCGTTTACGCAAC
ACCGGCTACTTTAAAAGTGTAAGTGTCTATACGGTTCGTTCCCAATTAGATCCTCTTGATTCTAACGACCTTTATCGAGATGTTTTTATTGAAGTCAAAG
AGACTGAAACAGGAAATCTTGGGCTATTCTTAGGATTCAGCTCCATTGACCATTTATTTGGAGGGGCAGAAATTGCAGAAAGCAACTTTGATTTATTTGG
AGCCCGAAACTTTCTCAAAAAAGGATTCAAATCTTTAAGAGGTGGTGGAGAATACCTCTTCCTAAAAGCTAATTTAGGAGATAAGGTCACCGATTACACT
GTTAAATGGACGAAACCACACTTCTTAAATACCCCTTGGATTCTTGGAGTAGAATTAGATAAATCAATTAATAAAGCTTTATCAAAAGACTACTCTGTGG
ATACCTATGGAGGGAATATCAGTACCACCTACATTCTTAACGATAAGTTAAAATATGGGATGTATTACCGTGGTAGCCAAACAAGCTTAAGTTTGCGCAA
AAAAACGTCCAGCTCTAATAGACCTGGACCAGATTTAGATAGTAATAAAGGATTTGTTTCCGCAGCGGGACTCAATGTTCTCTATGATTCTATTGATAAT
CCTAGAAAACCTACTATGGGAATCCGCAGCTCCTTAAACTTTGAATTATCTGGTTTAGGCGGAACTTACCAATTTACTAAACTAACAGCTAGTGGTTCTA
TCTATCGCTTATTAACTAAAAAAGGTGTTTTGAAAGTCCGTGCAGAAGCTAAGTTTATCAAACCTTTCGGAACAACAACTGCACAAGGCATTCCTGTCAG
CGAACGGTTCTTCTTAGGAGGTGAAACCACTGTTCGCGGTTACAAACCTTTTATTATTGGACCGAAATTTTCTCCTACTGAACCACAAGGAGGCTTGTCT
TCCCTACTATTAACAGAAGAATTTCAATATCCTTTGATTTCTCAACCTTGCATTAATGCCTTTGTATTTCTAGATTCCGGATTCATTGGGATAGAAGAGT
ACACTATTCGCCTGAAAGACCTTTGCAGTAGCGCCGGATTTGGTCTACGCTTTGATATGATGAATAATGTGCCAATTATGCTAGGCTGGGGTTGGCCGTT
CCGCCCAACAGAAATCCTCAATAATGAAAAAATTGATGTATCTCAAAGATTCTTTTTTGCCTTGGGAGGAGTATTCTAG
SEQ ID 57:
MKKFLLLSLMSLSSLPTFAANSTGTIGIVNLRRCLEESALGKKESAEFEKMKNQFSNSMGKMEEELSSIYSKLQDDDYMEGLSETAAAELRKKFEDLSAE
YNTAQGQYYQILNQSNLKRMQKIMEEVKKASETVRIQEGLSVLLNEDIVLSIDSSADKTDAVIKVLDDSFQNN
SEQ ID 58:
ATGAAAAAGTTCTTATTACTTAGCTTAATGTCTTTGTCATCTCTACCTACATTTGCAGCTAATTCTACAGGCACAATTGGAATCGTTAATTTACGTCGCT
GCCTAGAAGAGTCTGCTCTTGGGAAAAAAGAATCTGCTGAATTCGAAAAGATGAAAAACCAATTCTCTAACAGCATGGGGAAGATGGAGGAAGAACTGTC
TTCTATCTATTCCAAGCTCCAAGACGACGATTACATGGAAGGTCTATCCGAGACCGCAGCTGCCGAATTAAGAAAAAAATTCGAAGATCTATCTGCAGAA
TACAACACAGCTCAAGGGCAGTATTACCAAATATTAAACCAAAGTAATCTCAAGCGCATGCAAAAGATTATGGAAGAAGTGAAAAAAGCTTCTGAAACTG
TGCGTATTCAAGAAGGCTTGTCAGTCCTTCTTAACGAAGATATTGTCTTATCTATCGATAGTTCGGCAGATAAAACCGATGCTGTTATTAAAGTTCTTGA
TGATTCTTTTCAAAATAATTAA
SEQ ID 59:
MNKLLNFVSRTFGGDAALNMINKSSDLILAMWMLGVVLMIILPLPPAMVDFMITINLAISVFLLMVALYIPSALQLSVFPSLLLITTMFRLGINISSSRQ
ILLHAYAGHVIQAFGDFVVGGNYVVGFIIFLIITIIQFIVVTKGAERVAEVAARFRLDAMPGKQMAIDADLRAGMIDATQARDKRSQIQKESELYGAMDG
AMKFIKGDVIAGIVISLINIVGGLVIGVTMKGMTMAQAAHIYTLITIGDGLVSQIPSLLISLTAGIVTTRVSSDKDTNLGKEISSQLVKEPRALLLSAGA
TLGIGFFKGFPLWSFALMAVLFAVLGILLITKKNSPGKKGGASSTTTVGAADGAAASGENSDDYALTLPVILELGKDLSKLIQQRTKSGQSFVDDMIPKM
RQALYQDIGIRYPGIHVRTDSPSLEGNDYMILLNEVPYVRGKIPPNHVLTNEVEENLSRYNLPFITYKNAAGLPSTWVSTDALTILEKAAIKYWSPLEVI
ILHLSYFFHRNSQEFLGIQEVRSMIEFMERSFPDLVKEVTRLIPLQKLTEIFKRLVQEQISIKDLRTILESLSEWAQTEKDTVLLTEYVRSSLKLYISFK
FSQGQSAISVYLLDPEIEEMIRGAIKQTSAGSYLALDPDSVNLILKSMRMTITPTPPGGQPPVLLTAIDVRRYVRKLIETEFPDIAVISYQEVLPEIRIQ
PLGRIQIF
SEQ ID 60:
ATGAACAAGCTACTCAACTTTGTCAGTAGAACATTCGGGGGAGATGCGGCCCTGAATATGATAAACAAGTCCAGTGACCTGATCCTCGCCATGTGGATGT
TAGGCGTGGTCTTGATGATCATTTTGCCATTGCCTCCAGCTATGGTGGACTTTATGATCACCATTAACTTGGCGATCTCTGTGTTCCTGCTGATGGTTGC
CTTGTATATTCCCAGCGCATTACAACTTTCTGTTTTCCCCTCCTTACTCTTAATCACCACAATGTTCCGATTGGGGATTAACATTTCTTCCTCCCGACAA
ATTCTCCTTCATGCTTATGCTGGTCACGTGATCCAAGCCTTCGGAGACTTCGTCGTTGGAGGAAACTATGTCGTTGGATTTATTATCTTCCTAATCATCA
CCATCATTCAGTTTATCGTGGTAACAAAAGGTGCGGAGAGGGTCGCTGAGGTAGCTGCTCGATTCCGATTAGATGCCATGCCTGGTAAACAGATGGCCAT
CGATGCCGACCTACGAGCAGGAATGATTGATGCGACACAAGCTCGTGATAAGCGATCTCAGATTCAGAAAGAAAGTGAACTTTATGGAGCTATGGACGGA
GCCATGAAGTTCATTAAGGGAGACGTGATCGCAGGGATTGTTATCTCCTTGATTAACATCGTAGGAGGATTAGTCATCGGAGTGACCATGAAGGGCATGA
CGATGGCTCAAGCCGCGCACATCTACACGTTGATTACGATCGGTGACGGGTTAGTTTCTCAAATCCCCTCTCTGTTAATCTCTTTAACAGCTGGTATCGT
AACCACTCGAGTATCTAGTGATAAAGACACTAACCTTGGTAAGGAAATTTCTAGCCAGTTGGTTAAAGAACCTCGGGCACTTCTCCTATCCGCAGGCGCA
ACCTTAGGAATCGGATTCTTCAAAGGTTTCCCTTTATGGTCATTTGCTTTAATGGCCGTTCTCTTTGCAGTATTAGGTATTCTGTTAATCACTAAGAAAA
ACTCTCCAGGGAAAAAAGGCGGAGCCAGCTCTACTACTACAGTAGGTGCCGCTGATGGAGCTGCGGCTTCAGGAGAAAATTCTGATGATTATGCTCTGAC
TCTTCCTGTAATTCTTGAACTTGGAAAAGATCTTTCTAAACTCATCCAACAACGAACCAAATCGGGGCAAAGTTTTGTGGATGATATGATTCCTAAAATG
CGTCAGGCTCTCTATCAGGATATTGGAATTCGTTATCCAGGAATCCATGTACGTACAGACTCCCCTTCCTTGGAAGGTAATGACTATATGATTCTGCTGA
ATGAGGTTCCCTACGTTCGCGGAAAAATTCCACCAAATCATGTGTTAACAAATGAAGTAGAAGAAAACTTATCTCGGTATAACTTACCTTTTATTACTTA
CAAAAATGCTGCAGGATTGCCTTCCACTTGGGTTAGTACAGATGCTCTCACTATCTTAGAGAAAGCTGCGATTAAATACTGGTCTCCTTTGGAAGTGATT
ATTCTTCACTTGTCCTACTTCTTCCATAGAAATTCTCAAGAGTTCTTAGGCATTCAGGAAGTACGCTCTATGATTGAATTTATGGAACGTTCCTTCCCTG
ATCTTGTTAAAGAGGTTACCCGTCTTATTCCTCTACAGAAGCTTACAGAAATCTTTAAGCGTTTAGTTCAAGAACAAATATCCATTAAGGATTTACGAAC
TATTTTGGAATCTTTGAGCGAATGGGCACAGACGGAAAAAGATACAGTATTACTTACTGAATATGTGCGCTCTTCCTTGAAACTCTATATCAGCTTCAAG
TTCTCTCAAGGGCAATCCGCTATTTCTGTATATCTACTCGATCCTGAAATTGAAGAGATGATCCGCGGAGCAATCAAACAAACTTCTGCAGGATCTTATT
TGGCTTTAGATCCAGATTCTGTAAACCTCATCTTAAAATCTATGCGGATGACTATTACTCCTACACCTCCTGGAGGACAGCCTCCTGTGCTGTTGACAGC
AATTGATGTCAGACGCTATGTACGGAAATTGATAGAGACAGAATTCCCTGATATCGCTGTGATTTCTTACCAAGAAGTTTTACCTGAAATTAGAATCCAG
CCTTTGGGAAGAATTCAAATTTTCTAA
SEQ ID 61:
MTASGGAGGLGSTQTVDVARAQAAAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKGEKFESLEARRKPTADKAEKKSESTEEKGDTPLEDRF
TEDLSEVSGEDFRGLKNSFDDDSSPDEILDALTSKFSDPTIKDLALDYLIQTAPSDGKLKSTLIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTSPS
SLRSLYFQVTSSPSNCANLHQMLASYLPSEKTAVMEFLVNGMVADLKSEGPSIPPAKLQVYMTELSNLQALHSVNSFFDRNIGNLENSLKHEGHAPIPSL
TTGNLTKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQTEVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDYPKPGDFPRSSFSSTPP
HAPVPQSEIPTSPTSTQPPSP
SEQ ID 62:
ATGACTGCATCAGGAGGAGCTGGAGGGCTAGGCAGCACCCAAACAGTAGACGTTGCGCGAGCACAAGCTGCTGCAGCTACTCAAGATGCACAAGAGGTTA
TCGGCTCTCAGGAAGCTTCTGAGGCAAGTATGCTCAAAGGATGTGAGGATCTCATAAATCCTGCAGCTGCAACCCGAATCAAAAAAAAAGGAGAGAAGTT
TGAATCATTAGAAGCTCGTCGCAAACCAACAGCGGATAAAGCAGAAAAGAAATCCGAGAGCACAGAGGAAAAAGGCGATACTCCTCTTGAAGATCGTTTC
ACAGAAGATCTTTCCGAAGTCTCCGGAGAAGATTTTCGAGGATTGAAAAATTCGTTCGATGATGATTCTTCTCCTGACGAAATTCTCGATGCGCTCACAA
GTAAATTTTCTGATCCCACAATAAAGGATCTAGCTCTTGATTATCTAATTCAAACAGCTCCCTCTGATGGGAAACTTAAGTCCACTCTCATTCAGGCAAA
GCATCAACTGATGAGCCAGAATCCTCAGGCGATTGTTGGAGGACGCAATGTTCTGTTAGCTTCAGAAACCTTTGCTTCCAGAGCAAATACATCTCCTTCA
TCGCTTCGCTCCTTATATTTCCAAGTAACCTCATCCCCCTCTAATTGCGCTAATTTACATCAAATGCTTGCTTCTTACTTGCCATCAGAGAAAACCGCTG
TTATGGAGTTTCTAGTAAATGGCATGGTAGCAGATTTAAAATCGGAGGGCCCTTCCATTCCTCCTGCAAAATTGCAAGTATATATGACGGAACTAAGCAA
TCTCCAAGCCTTACACTCTGTAAATAGCTTTTTTGATAGAAATATTGGGAACTTGGAAAATAGCTTAAAGCATGAAGGACATGCCCCTATTCCATCCTTA
ACGACAGGAAATTTAACTAAAACCTTCTTACAATTAGTAGAAGATAAATTCCCTTCCTCTTCCAAAGCTCAAAAGGCATTAAATGAACTGGTAGGCCCAG
ATACTGGTCCTCAAACTGAAGTTTTAAACTTATTCTTCCGCGCTCTTAATGGCTGTTCGCCTAGAATATTCTCTGGAGCTGAAAAAAAACAGCAGCTGGC
ATCGGTTATCACAAATACGCTAGATGCGATAAATGCGGATAATGAGGATTATCCTAAACCAGGTGACTTCCCACGATCTTCCTTCTCTAGTACGCCTCCT
CATGCTCCAGTACCTCAATCTGAGATTCCAACGTCACCTACCTCAACACAGCCTCCATCACCCTAA
SEQ ID 63:
MKKTKHLISKIMFSLVSLFVGGFLLKAPAPTQSADTFQTLIESKEPVIFTKQCGDNVTQILCDAIDSAKKDIFLSIYDLSAPAITTSLKKQVSARIPVCI
HYQRISKNAEFSQSPYLTLGEHPPMHRKLMHQKTMAIDGELAWIGSANFTLASLEKSANLIIGLKSAEICHFIKTQTSGRCFINNQLIEYFSFDGGSSAA
LETVLHHIRSAKESIQVGMFALTLPQIIAELNAAQNCGVDVVILVDKGYKSFTVQQIKQLEHPSLSIYEKVTPYQLHHKFGIFDKKTLITGSVNWSENGF
LINTEDMIVIENLTEKQQSKIQAIWEGLVRECALYYSPDQEEKEKDPLIIPFPPSEKKQAA
SEQ ID 64:
ATGAAAAAAACAAAACACCTTATTTCCAAAATAATGTTCAGCTTAGTTTCCCTTTTTGTTGGAGGATTTTTACTAAAAGCCCCAGCCCCGACTCAATCTG
CTGATACCTTCCAAACGCTTATTGAATCCAAGGAACCTGTTATCTTCACCAAACAGTGTGGAGACAATGTAACGCAAATACTATGTGATGCGATAGACTC
TGCAAAAAAAGATATTTTTCTCAGTATTTATGACCTATCTGCTCCCGCTATCACGACAAGTTTGAAAAAACAAGTGTCCGCTCGCATTCCTGTATGTATT
CATTACCAACGTATCTCTAAAAATGCGGAGTTCTCTCAGTCTCCCTATCTTACCTTGGGAGAACATCCTCCCATGCACAGAAAACTCATGCATCAAAAAA
CTATGGCAATAGATGGAGAACTCGCTTGGATCGGATCTGCTAATTTTACATTAGCTTCGTTAGAGAAGAGCGCTAACCTAATAATTGGATTAAAAAGCGC
AGAAATTTGTCATTTTATTAAAACGCAAACCTCTGGTCGGTGCTTTATTAACAATCAACTCATCGAGTATTTTTCCTTTGATGGGGGGAGTTCTGCTGCT
CTAGAAACAGTTCTTCACCATATTCGATCAGCGAAAGAATCCATCCAAGTAGGTATGTTTGCTCTCACTTTACCTCAGATTATTGCTGAATTGAATGCCG
CACAAAACTGTGGTGTTGATGTAGTGATCCTCGTCGACAAAGGATACAAATCCTTTACCGTACAGCAAATTAAGCAATTGGAACATCCTAGTCTCTCTAT
TTATGAAAAGGTAACCCCGTACCAACTACATCATAAATTTGGCATTTTCGATAAAAAGACGCTAATTACAGGATCTGTCAATTGGTCTGAGAATGGCTTC
CTTATTAATACAGAAGACATGATTGTCATTGAAAATCTGACAGAAAAACAGCAAAGCAAAATACAGGCGATATGGGAAGGATTAGTAAGAGAGTGTGCTT
TGTATTACTCCCCAGATCAAGAGGAAAAAGAAAAAGATCCTTTAATCATTCCGTTCCCTCCTAGCGAAAAAAAACAAGCTGCTTGA
SEQ ID 65:
MGKFFASYLLILAPFFLQSCSAPSRTTLEGVRMTIPYRIVFGEALSPDAFQQAQKEIDRVFDHIDQTFNNWNPLSEISRINRTTKQTPIPLSPALFAFLC
EIDHFHAFSDGRFDPTLGALKSLWLLHLKSHTIPSQELQHLYKHSSGWHLISLDKTQQTLRKLSPLVQLDLCGTVKGFAVDLLGTACAQFCQNYYVEWGG
EIKTKGKHPSGRSWAVASSATPEILHLHDHAIATSGSQYQRWHVDNKTYTHILDPLTGTPLEDSSHPILAVSVINESCAFADAMATALTTFSSKQEALDW
ANKKHLCAYITDKNVS
SEQ ID 66:
ATGGGAAAGTTTTTTGCGTCATACCTCCTGATCCTAGCCCCCTTCTTCCTCCAATCCTGTTCAGCTCCTTCAAGAACTACTCTTGAAGGGGTCCGTATGA
CAATTCCTTATCGCATTGTATTTGGAGAAGCACTTTCTCCAGATGCATTCCAACAAGCGCAAAAGGAAATTGATCGAGTGTTTGATCATATCGATCAAAC
TTTTAATAATTGGAATCCTCTATCCGAAATTTCCCGTATTAATCGCACCACAAAACAAACCCCTATCCCCTTATCGCCAGCACTCTTTGCTTTTCTATGC
GAAATAGACCATTTCCACGCCTTCTCTGATGGCCGTTTTGATCCCACCTTAGGCGCTTTAAAAAGCTTATGGCTACTGCACCTAAAATCCCATACCATCC
CTTCTCAAGAGCTCCAACACCTCTACAAACACAGCTCTGGATGGCATCTGATTTCTCTTGATAAAACCCAGCAAACTTTAAGGAAACTTTCGCCTCTCGT
CCAATTAGATCTCTGCGGAACTGTAAAAGGTTTTGCTGTAGATCTATTAGGAACAGCTTGTGCTCAATTCTGTCAAAATTACTACGTAGAATGGGGAGGA
GAAATCAAAACCAAAGGGAAACATCCTTCCGGAAGATCTTGGGCTGTCGCTTCATCAGCTACCCCAGAGATTCTTCATCTGCATGATCATGCTATAGCGA
CGAGCGGGAGTCAATATCAACGATGGCATGTGGACAACAAAACCTACACCCACATTCTTGACCCATTAACGGGAACTCCTCTAGAAGATAGCAGCCATCC
CATCCTTGCAGTTTCCGTGATCAACGAAAGCTGCGCCTTTGCGGATGCTATGGCTACTGCACTGACGACCTTCTCCTCTAAACAAGAAGCTCTTGACTGG
GCAAATAAGAAACATCTTTGCGCATATATTACCGATAAGAACGTTTCATAG
SEQ ID 67:
MSFFHTRKYKLILRGLLCLAGCFLMNSCSSSRGNQPADESIYVLSMNRMICDCVSRITGDRVKNIVLIDGAIDPHSYEMVKGDEDRMAMSQLIFCNGLGL
EHSASLRKHLEGNPKVVDLGQRLLNKNCFDLLSEEGFPDPHIWTDMRVWGAAVKEMAAALIQQFPQYEEDFQKNADQILSEMEELDRWAARSLSTIPEKN
RYLVTGHNAFSYFTRRYLSSDAERVSGEWRSRCISPEGLSPEAQISIRDIMRVVEYISANDVEVVFLEDTLNQDALRKIVSCSKSGQKIRLAKSPLYSDN
VCDNYFSTFQHNVRTITEELGGTVLE
SEQ ID 68:
ATGTCTTTTTTTCATACTAGAAAATATAAGCTTATCCTCAGAGGACTCTTGTGTTTAGCAGGCTGTTTCTTAATGAACAGCTGTTCCTCTAGTCGAGGAA
ATCAACCCGCTGATGAAAGCATCTATGTCTTGTCTATGAATCGCATGATTTGTGATTGCGTGTCTCGCATAACTGGGGATCGAGTCAAGAATATTGTTCT
GATTGATGGAGCGATTGATCCTCATTCATATGAGATGGTGAAGGGGGATGAAGACCGAATGGCTATGAGCCAGCTGATTTTTTGCAATGGTTTAGGTTTA
GAGCATTCAGCTAGTTTACGTAAACATTTAGAGGGTAACCCAAAAGTCGTTGATTTAGGTCAACGTTTGCTTAACAAAAACTGTTTTGATCTTCTGAGTG
AAGAAGGATTCCCTGACCCACATATTTGGACGGATATGAGAGTATGGGGTGCTGCTGTAAAAGAGATGGCTGCGGCATTAATTCAACAATTTCCTCAATA
TGAAGAAGATTTTCAAAAGAATGCGGATCAGATCTTATCAGAGATGGAGGAACTTGATCGTTGGGCAGCGCGTTCTCTCTCTACGATTCCTGAAAAAAAT
CGCTATTTAGTCACAGGCCACAATGCGTTCAGTTACTTTACTCGTCGGTATCTATCCTCTGATGCGGAGAGAGTGTCTGGGGAGTGGAGATCGCGTTGCA
TTTCTCCAGAAGGGTTGTCTCCTGAGGCTCAGATTAGTATCCGAGATATTATGCGTGTAGTGGAGTATATCTCTGCAAACGATGTAGAAGTTGTCTTTTT
AGAGGATACCTTAAATCAAGATGCTTTGAGAAAGATTGTTTCTTGCTCTAAGAGCGGACAAAAGATTCGTCTCGCTAAGTCTCCTTTATATAGCGATAAT
GTCTGTGATAACTATTTTAGCACGTTCCAGCACAATGTTCGCACAATTACAGAAGAATTGGGAGGGACTGTTCTTGAATAG
SEQ ID 69:
MQNILRTSSCRYMFLLGIRSVWNRVAVVNNFRGSSWKIVAIPSCILFTLIFHLPRWLIDFGVCTNLACSLSIIFWVFSLRSSASARIFPSLLLYLCLLRL
GLNLASTRWILSSGWASPLIFALGNFFSLGSIPVALTVCLLLFLVNFLVITKGAERIAEVRARFSLEALPGKQMSLDADIAAGRIGYSRASVKKSSLLEE
SDYFSAMEGVFRFVKGDAIMSWVLLGVNILAALFLGRATHVGDLWLTVLGDALVSQIPALLTSCAAATLIAKVGEKESLAQHLLDYYEQSRQSFLFIALI
LCGMACIPGAPKALILGFSVLLFLGYKNPSSGETLLFQKERVEFVLPDEGVGNPANLYKDARNQIYQELGVVFPEAIVVRHVTGSSPRLIFSGQEVALRE
LSCPAILESIRQLAPETISERFVTRLVDEFREHAFLSIEEILPLKISENSLIFLLRALVRERVSLHLFPKILEAIDVYGSQPKNSQELVECVRKYLGKQI
GLSLWNRQDVLEVITIDSLVEQFVRDSQEKVVLDLNEKVVAQVKHLLRVGEGNFRAIVTGSETRKELKRIVDPYFPDLLVLAHSELPEEIPITLLGAVSD
EVLLS
SEQ ID 70:
ATGCAAAATATTCTTCGAACTTCTTCTTGCAGATATATGTTTTTGCTGGGTATTCGTTCGGTGTGGAATCGGGTGGCTGTTGTGAATAACTTTAGAGGAA
GTTCATGGAAAATTGTAGCAATCCCCAGTTGTATACTGTTTACTTTGATATTCCATTTACCTAGATGGCTGATTGATTTTGGGGTATGTACAAATTTAGC
GTGCTCCTTGTCGATCATTTTTTGGGTGTTTTCTCTACGCTCTTCAGCTTCGGCTCGTATTTTCCCTTCTCTCCTTTTGTATCTTTGTCTATTGCGACTT
GGCCTGAATTTAGCCTCCACCCGATGGATTTTATCTTCTGGATGGGCTTCTCCTTTAATTTTTGCGTTAGGGAATTTCTTTTCCCTTGGGAGCATCCCGG
TTGCTCTTACGGTATGTTTACTCCTGTTTTTAGTGAATTTTCTCGTCATAACTAAAGGAGCAGAGCGTATTGCGGAAGTGCGAGCTCGTTTTTCATTAGA
AGCGCTCCCAGGTAAACAAATGTCTTTAGATGCTGATATTGCTGCTGGAAGGATCGGGTATAGCAGAGCGTCTGTTAAAAAAAGCTCTCTTTTAGAAGAG
AGTGATTACTTCTCCGCCATGGAGGGCGTATTCCGCTTTGTAAAAGGCGATGCGATAATGAGTTGGGTGTTGTTAGGAGTGAATATCCTAGCTGCTCTGT
TTTTAGGACGAGCTACTCATGTTGGCGATTTGTGGTTAACTGTATTAGGCGATGCTTTAGTGAGTCAAATTCCAGCATTGCTTACATCGTGTGCAGCAGC
AACGCTTATAGCTAAAGTTGGGGAAAAAGAAAGTCTAGCGCAGCATCTGCTAGATTATTATGAGCAGAGTCGCCAGAGTTTTCTTTTTATCGCTTTGATC
CTATGTGGGATGGCTTGTATTCCAGGAGCTCCTAAAGCTCTGATCCTAGGTTTTTCAGTTTTATTATTCTTAGGGTATAAGAATCCTTCTTCAGGAGAGA
CTCTTCTCTTCCAGAAAGAACGGGTAGAGTTTGTATTGCCTGATGAGGGAGTGGGAAATCCTGCTAATTTGTACAAGGACGCCCGCAATCAGATTTATCA
AGAGTTAGGCGTAGTTTTCCCGGAAGCTATTGTTGTACGTCATGTAACAGGATCTTCTCCACGTTTAATCTTTTCTGGGCAAGAGGTCGCTTTGAGAGAG
CTGTCTTGCCCAGCTATACTAGAATCGATTAGGCAGCTAGCTCCAGAAACGATCAGTGAACGCTTCGTTACTCGCTTAGTTGATGAGTTTCGAGAGCATG
CATTCTTATCGATAGAAGAGATCCTTCCGTTAAAAATATCAGAGAATTCTTTGATTTTCTTATTGAGAGCTCTTGTTAGAGAACGAGTGTCTTTGCATTT
ATTCCCTAAGATTCTCGAAGCTATAGATGTATATGGCTCTCAACCAAAGAATTCTCAGGAATTGGTAGAGTGTGTACGAAAATATCTTGGGAAGCAAATT
GGTTTATCCTTATGGAATCGCCAAGATGTCTTAGAGGTAATTACGATAGACTCTCTGGTTGAGCAGTTTGTGAGAGATTCACAAGAAAAGGTTGTGTTGG
ATTTAAATGAAAAAGTAGTTGCTCAGGTGAAGCATTTATTGCGGGTAGGGGAGGGGAATTTTCGAGCTATCGTAACGGGATCCGAAACAAGAAAAGAACT
GAAACGCATAGTGGATCCTTATTTCCCAGATTTATTGGTTTTAGCACATAGCGAACTTCCAGAAGAGATCCCTATAACTTTGTTAGGAGCGGTGTCTGAT
GAGGTTTTATTATCATAA
SEQ ID 71:
MVLLYSQASWDKRSKADALVLPFWMKNSKAQEAAVVDEDYKLVYQNALSNFSGKKGETAFLFGNDHTKEQKIVLLGLGKSEEVSGTTVLEAYAQATTVLR
KAKCKTVNILLPTISQLRFSVEEFLTNLAAGVLSLNYNYPTYHKVDTSLPFLEKVTVMGIVSKVGDKIFRKEESLFEGVYLTRDLVNTNADEVTPEKLAA
VAKDLAGEFASLDVKILDRKAILKEKMGLLAAVAKGAAVEPRFIVLDYQGKPKSKDRTVLIGKGVTFDSGGLDLKPGKAMITMKEDMAGAATVLGIFSAL
ASLELPINVTGIIPATENAIGSAAYKMGDVYVGMTGLSVEIGSTDAEGRLILADAISYALKYCNPTRIIDFATLTGAMVVSLGESVAGFFANNDVLARDL
AEASSETGEALWRMPLVEKYDQALHSDIADMKNIGSNRAGSITAALFLQRFLEDNPVAWAHLDIAGTAYHEKEELPYPKYATGFGVRCLIHYMEKFLSK
SEQ ID 72:
GTGGTATTACTCTATTCTCAAGCGAGTTGGGATAAACGATCAAAAGCGGATGCTCTTGTTCTTCCTTTTTGGATGAAGAATTCTAAAGCTCAAGAAGCTG
CGGTTGTTGATGAGGACTACAAGCTTGTCTATCAAAACGCATTATCCAATTTTTCAGGGAAGAAAGGGGAAACGGCTTTTCTTTTTGGAAATGATCACAC
AAAAGAACAAAAAATTGTTCTTCTTGGTCTAGGGAAGAGCGAAGAAGTATCCGGAACAACCGTTTTAGAAGCCTACGCTCAGGCTACTACTGTTTTAAGA
AAAGCTAAGTGTAAGACTGTAAATATTTTACTCCCAACAATTTCACAGTTGCGCTTCTCCGTAGAAGAGTTTTTAACGAACTTGGCAGCAGGGGTGCTAT
CTCTGAACTATAATTACCCAACCTATCACAAAGTGGATACGTCTTTGCCTTTCCTAGAGAAAGTGACTGTAATGGGTATTGTCTCTAAGGTAGGGGACAA
GATCTTTAGAAAAGAAGAGAGCCTATTTGAAGGGGTATATTTAACTAGAGATTTAGTGAATACCAATGCAGATGAAGTCACTCCAGAAAAACTTGCTGCG
GTAGCAAAAGATCTAGCAGGGGAGTTCGCGAGTCTGGATGTAAAAATTCTAGATAGGAAGGCGATATTAAAAGAAAAAATGGGATTGTTGGCTGCTGTTG
CCAAGGGCGCTGCTGTTGAGCCTCGGTTTATTGTTCTGGATTACCAAGGTAAACCTAAATCTAAAGATAGAACCGTACTCATTGGTAAAGGGGTAACATT
CGATTCCGGAGGACTAGATTTGAAACCTGGGAAGGCAATGATTACCATGAAGGAAGACATGGCTGGAGCGGCTACCGTTCTAGGAATTTTTTCTGCTTTA
GCTTCCTTAGAGCTTCCGATCAATGTGACCGGGATCATTCCAGCTACAGAGAATGCAATTGGATCGGCTGCCTATAAGATGGGAGATGTATATGTTGGAA
TGACCGGCCTTTCTGTAGAAATTGGCAGCACTGATGCGGAAGGGCGTTTGATTTTAGCAGATGCCATCTCCTATGCTTTGAAATATTGTAATCCTACCCG
CATCATTGACTTTGCTACCTTGACGGGTGCTATGGTTGTTTCTTTAGGAGAATCTGTGGCTGGATTTTTTGCAAATAACGACGTGTTGGCAAGAGATCTA
GCAGAAGCTTCATCAGAGACGGGGGAAGCTCTATGGAGAATGCCTTTGGTAGAGAAATATGACCAGGCACTTCATTCAGATATTGCAGATATGAAAAATA
TCGGCAGCAATCGTGCAGGATCGATTACTGCAGCGCTATTTTTACAACGTTTCCTCGAAGACAATCCAGTAGCATGGGCACATTTGGACATTGCAGGTAC
TGCTTACCATGAAAAAGAAGAGTTGCCTTACCCCAAATATGCAACAGGATTTGGTGTGCGTTGTTTAATTCATTATATGGAGAAATTCCTATCTAAATAG
SEQ ID 73:
MFSSAIVILTAIFVLCSGFVSLSHIALFSLPSSLIAHYSHSKNRQLRQIANLMAYPNHLLMTLVFFDIGINIGVQNCIATLVGDSASLLLTVGVPLALTL
VLGEIVPKVIAIPYNARIAKIVTPIIFASTKSFRPIFDWAISGINFIVQKMLARQESDFIQPQELKEVLRSCKDFGVVNHEESRLLFGYLSMEEGSIKER
MTPKQEIIFYDVLTPIENLYKLFSGPKQSYSKVLVCKGGLQNLLGVCSAKLLLLYKEKLQSAEELLPLLRKPHYIPETVSAKTALYHLAGEDCGLGIIID
EYGSIEGLITQNDLFKIVSDGVAHNRPSFKQFAHSDKNVVIAAGTYELSDFYDLFGVDLPTTANCVTIGGWLTEQLGEIPETGTKFAWGQFVFQILDAAP
NCVKRVYIRKTHGN
SEQ ID 74:
ATGTTTTCTTCAGCAATTGTTATTCTAACTGCAATTTTTGTCTTGTGCTCGGGGTTTGTTTCTTTATCGCATATAGCTTTATTCTCGCTCCCTTCTTCCC
TTATTGCTCATTACAGTCACTCAAAAAATAGGCAGCTCCGACAAATTGCCAATCTTATGGCCTACCCCAATCATTTGCTCATGACCCTAGTCTTCTTCGA
CATAGGGATTAATATTGGAGTGCAAAACTGCATAGCAACCTTAGTAGGCGATTCGGCATCTCTATTGCTTACCGTAGGAGTTCCCCTCGCTTTGACACTA
GTTTTGGGAGAAATTGTCCCTAAGGTTATCGCAATCCCTTACAATGCACGAATTGCAAAGATTGTAACCCCAATCATCTTTGCCTCAACTAAAAGCTTCC
GCCCTATATTTGATTGGGCTATCTCGGGTATCAATTTTATCGTTCAGAAAATGTTGGCCCGTCAAGAAAGTGATTTTATTCAACCCCAAGAATTAAAAGA
AGTCCTCCGAAGCTGTAAAGATTTCGGAGTTGTAAATCATGAGGAAAGTCGTCTTCTATTTGGCTATCTATCCATGGAAGAAGGTAGCATTAAAGAACGC
ATGACGCCCAAACAAGAAATCATTTTTTATGATGTCCTTACTCCGATTGAAAATTTATATAAACTCTTCTCTGGACCTAAACAAAGCTATTCCAAAGTTC
TAGTTTGTAAAGGTGGTCTACAAAATCTCTTAGGAGTTTGTTCTGCAAAATTGCTTCTTCTCTACAAAGAAAAATTACAATCTGCCGAAGAACTCTTGCC
TCTCCTTCGTAAACCTCACTACATTCCTGAAACAGTATCAGCTAAGACAGCTTTGTATCATCTAGCAGGAGAAGACTGTGGTTTAGGTATTATCATTGAT
GAATATGGGTCTATAGAAGGATTGATCACCCAAAATGATCTATTTAAAATAGTCTCTGATGGGGTAGCTCATAATCGCCCATCTTTTAAACAATTCGCTC
ACTCAGACAAGAATGTTGTTATTGCTGCAGGCACCTATGAGCTTTCTGATTTCTATGACCTGTTTGGAGTTGATCTTCCTACTACAGCTAATTGCGTTAC
CATAGGCGGATGGCTGACAGAACAATTAGGAGAAATCCCTGAAACAGGAACAAAATTCGCTTGGGGACAATTTGTATTCCAAATACTAGACGCGGCTCCT
AATTGTGTGAAACGGGTGTATATAAGGAAAACCCATGGAAACTAA
SEQ ID 75:
MRKFWLLASFGLLSLTTTTLSSCAVSNSGSYNARLYTKGSKAKGVVAMLPVFYRTEKSAELLPWNLQAEFSEEISRRLHSSDKLLLIKHHASAGVAAQFF
SPTPNISPELATQLLPAEFVVAAEILEQKTTEDVLNPSISASVRVRVFDIRHNKVSMIYQEILDASQSLASGSNDYHRYGWRSKNFDSTPMGLMHQRLFR
EIVARVEGYVCANYS
SEQ ID 76:
ATGCGAAAATTCTGGTTACTTGCTTCTTTCGGCCTTTTGTCTTTAACTACGACTACTCTTTCTAGCTGTGCTGTATCTAATTCTGGCAGCTACAATGCTA
GACTATACACTAAAGGGAGCAAGGCTAAAGGAGTCGTCGCCATGCTACCTGTTTTTTATCGAACAGAAAAGTCTGCAGAACTACTCCCTTGGAATTTACA
AGCAGAGTTTTCCGAAGAGATTAGCAGACGTTTGCACTCTTCTGATAAACTACTTTTAATCAAACACCACGCTTCAGCTGGTGTTGCTGCACAATTTTTT
TCTCCTACTCCTAATATTTCGCCCGAATTAGCGACTCAGCTGTTGCCTGCGGAATTCGTAGTTGCGGCAGAAATTTTAGAACAGAAAACAACGGAAGATG
TTTTAAACCCTTCTATTTCAGCATCTGTTCGTGTGCGAGTGTTTGATATTCGTCACAATAAAGTCTCTATGATATACCAAGAGATTTTAGACGCGAGTCA
ATCTCTCGCCTCTGGAAGCAACGATTATCATCGTTATGGCTGGCGTTCGAAAAACTTCGATTCGACTCCGATGGGCCTCATGCATCAGAGATTATTTAGA
GAGATTGTTGCTCGCGTAGAGGGATATGTCTGCGCAAACTACTCTTGA
SEQ ID 77:
MLVESQLGLEDVLEAFSERNFDIQSKSFIESFQDKKLRRTVIQRFLHHPLLHIHDIARAAYLLAALEEGVDLGYQFLCMHQTQSGAALLFRRAGFLWGGL
PYPGEHAEMAMLLSRIAEFYDTSYEQVQKMIAFQHALFSHERNIFPALWSQEGSRSNQEKTAVSKLLFCQKEARIEDQFTLTDMSLGFWMRRTPSFSAYV
SGSGCKSGVGAFLIGDVGVLNYGPCVGDPGECLGFGLCGQVKEFSCQEKDEEVSISFAGALSQPSSRRTGFSYLQDALFSTNSCYCIDITEQKCHVASSL
DRENQDAFFAIFCKGSQCQVCNGPKLRTGSPDSYKGPAYDVLIKGEKETVRILSSSPHMEIFSLQGKDRFWGSNFLINLPYTQNSINILFEKA
SEQ ID 78:
ATGCTAGTAGAATCGCAGTTAGGGTTAGAGGACGTATTAGAGGCGTTCTCTGAGAGGAATTTTGATATTCAAAGTAAGAGTTTCATAGAGTCTTTCCAGG
ATAAGAAGCTGCGAAGAACCGTTATACAGCGTTTTCTACATCATCCATTGTTACATATTCATGATATCGCTCGTGCCGCTTATTTGCTGGCAGCTTTGGA
AGAAGGGGTAGACTTAGGATACCAGTTCCTTTGTATGCATCAGACGCAGTCTGGAGCGGCTTTATTATTTCGTCGAGCAGGTTTTTTATGGGGAGGCCTT
CCTTATCCTGGGGAGCATGCTGAGATGGCTATGTTGTTGTCTCGTATTGCAGAGTTTTATGACACAAGCTACGAGCAAGTTCAAAAAATGATAGCTTTTC
AACACGCATTATTTTCTCATGAGAGAAACATTTTCCCTGCATTGTGGAGTCAAGAAGGCTCTAGATCCAACCAGGAAAAAACAGCTGTTAGTAAATTGTT
ATTTTGCCAAAAAGAAGCCCGTATAGAAGATCAGTTCACGCTAACAGATATGTCTCTTGGTTTTTGGATGCGCAGAACGCCTTCTTTTTCTGCTTATGTT
AGTGGTAGTGGTTGTAAGAGCGGAGTGGGGGCTTTTTTGATAGGAGATGTGGGGGTTCTCAACTATGGTCCTTGCGTTGGGGATCCAGGAGAATGTTTGG
GATTTGGTTTATGCGGCCAAGTGAAAGAGTTCTCATGTCAAGAAAAAGACGAAGAAGTATCAATATCTTTTGCAGGAGCTTTGTCACAGCCTTCTTCTAG
GAGAACAGGCTTTTCTTATTTGCAAGATGCTTTGTTTAGCACTAATTCATGTTATTGTATAGACATTACTGAGCAAAAGTGTCATGTTGCTTCTTCTTTG
GATAGGGAAAATCAGGATGCGTTTTTTGCTATCTTTTGTAAGGGATCGCAATGTCAAGTATGCAATGGTCCAAAATTGCGTACAGGATCTCCAGACTCTT
ATAAAGGCCCAGCCTATGATGTATTGATTAAAGGAGAAAAAGAGACTGTTCGGATTTTATCTTCTAGTCCGCATATGGAAATTTTTTCTTTACAAGGCAA
AGATCGGTTTTGGGGAAGTAATTTTTTGATCAATCTTCCCTACACACAAAATAGTATAAACATTTTATTTGAAAAGGCTTGA
SEQ ID 79:
MKMAFLRKIFVFVACVVSLNGFAHTIAIPDGDKKAKVLIHDNGYEMYEHLLAAISSAKYTVELCPCLAGGEILSTVLQRLEQRMEEVPALVSYILVQPTC
IDDNDRKNLKTLQENYPDRFFYLFSDWPPYCNVFFPNVTESHTKLSIVDGKYIFIGGSNLEDLQCSKGDVDLEVSDSPRAVIGGVLRPSAMRDQDVTIVS
EEYGALLRKEFCAHYALWKDFTQKLWLNKKLDDFRGIDPINLSIEKARSSFCAMIETSLCAVSVPLDKMHFIFSGPDESNNTIAEEYVRLINQAQHSIRI
AQMFFIPVAKIYDSLMAACWDRGVEIYLVTNGRTDRSPEITRSYAWGNRINYFPLTFGSRPLLWERFLYSPSRASMKFYVSEFYVANTQLHKKCMLVDDH
ILVIGSYNFGKKSNDCDYECIVVIDSKEAVSKAQVVFEKDLRLSKSVTHDDIINWYFDPVHYCLGYLEQRYMPS
SEQ ID 80:
ATGAAAATGGCTTTTTTACGGAAAATATTTGTATTTGTAGCTTGTGTTGTCTCGTTGAATGGTTTTGCACACACTATAGCTATTCCGGATGGAGACAAAA
AAGCTAAGGTTCTTATTCATGATAACGGCTATGAAATGTACGAACACCTGTTGGCCGCTATTAGTAGTGCTAAATATACTGTAGAATTGTGTCCTTGTTT
AGCAGGAGGAGAGATTTTATCCACAGTTCTTCAGCGCTTGGAGCAGCGTATGGAAGAAGTGCCTGCGCTTGTAAGCTACATATTGGTCCAACCTACATGT
ATTGATGATAATGATCGGAAGAATTTAAAAACTCTGCAAGAAAATTATCCTGACAGGTTTTTCTACCTGTTTTCAGATTGGCCACCGTATTGTAATGTAT
TTTTCCCTAACGTGACAGAGTCGCATACTAAGTTGTCCATTGTTGATGGGAAGTACATTTTTATCGGAGGTTCAAATTTAGAGGATCTTCAATGTTCTAA
AGGGGATGTGGATTTAGAAGTCTCTGATTCCCCTCGTGCTGTGATAGGAGGAGTGCTTCGGCCTTCAGCTATGCGAGATCAAGATGTAACGATTGTCTCG
GAAGAATATGGAGCATTGCTGAGAAAAGAATTTTGTGCTCACTATGCTTTGTGGAAGGATTTCACTCAAAAACTATGGTTAAACAAAAAATTAGATGATT
TTAGAGGCATTGATCCAATCAATCTTTCTATAGAAAAAGCTAGATCCTCTTTCTGTGCTATGATTGAGACGAGCCTTTGTGCTGTATCTGTACCTTTAGA
TAAAATGCATTTTATCTTTTCCGGACCGGATGAATCGAACAACACGATTGCTGAAGAATATGTTCGGCTGATTAACCAAGCTCAACATTCTATCCGGATA
GCGCAGATGTTTTTTATTCCGGTAGCGAAAATATATGATAGTCTCATGGCTGCTTGCTGGGATAGAGGCGTAGAAATCTATTTAGTAACCAATGGGAGAA
CGGATCGGAGTCCCGAAATCACTAGAAGCTATGCTTGGGGAAATCGAATTAATTATTTCCCATTGACTTTCGGTTCTCGGCCGCTTTTGTGGGAACGCTT
TTTGTATTCTCCCAGTCGAGCCTCTATGAAGTTTTATGTGAGCGAGTTTTATGTAGCTAATACACAACTGCATAAAAAGTGCATGCTTGTAGATGATCAT
ATTTTAGTTATAGGCAGTTACAATTTTGGAAAGAAGAGTAACGATTGCGATTACGAATGCATTGTGGTGATTGATTCAAAAGAAGCAGTCTCTAAAGCTC
AGGTAGTATTTGAAAAAGATTTGCGACTTTCTAAATCAGTGACTCATGATGACATTATAAACTGGTATTTTGATCCTGTACATTATTGTTTAGGGTACTT
AGAACAGAGATACATGCCATCTTAA
SEQ ID 81:
MQTSFHKFFLSMILAYSCCSLSGGGYAAEIMIPQGIYDGETLTVSFPYTVIGDPSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLTF
ENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATTNNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAIDAKSLTVQ
GISKLCVFQENTAQADGGACQVVTSFSAMANEAPIAFIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFDGNVARVGGGIYSYGNNAFL
NNGKTLELNNVASPVYIAAEQPTNGQASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSSNVAAGKGGAIYAKKLSVANCGPVQFLGNIAN
DGGAIYLGESGELSLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKITTLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTG
DIVFANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGSTLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPPAQDSHP
AIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKIDVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTANNGPYTLKATWTKTGYNP
GPERVASLVPNSLWGSILDIRSAHSAIQASVDGRSYCRGLWVSGVSNFFYHDRDALGQGYRYISGGYSLGANSYFGSSMFGLAFTEVFGRSKDYVVCRSN
HHACIGSVYLSTKQALCGSYLFGDAFIRASYGFGNQHMKTSYTFAEESDVRWDNNCLVGEIGVGLPIVITPSKLYLNELRPFVQAEFSYADHESFTEEGD
QARAFRSGHLMNLSVPVGVKFDRCSSTHPNKYSFMGAYICDAYRTISGTQTTLLSHQETWTTDAFHLARHGVIVRGSMYASLTSNIEVYGHGRYEYRDTS
RGYGLSAGSKVRF
SEQ ID 82:
ATGCAAACGTCTTTCCATAAGTTCTTTCTTTCAATGATTCTAGCTTATTCTTGCTGCTCTTTAAGTGGGGGGGGGTATGCAGCAGAAATCATGATTCCTC
AAGGAATTTACGATGGGGAGACGTTAACTGTATCATTTCCCTATACTGTTATAGGAGATCCGAGTGGGACTACTGTTTTTTCTGCAGGAGAGTTAACGTT
AAAAAATCTTGACAATTCTATTGCAGCTTTGCCTTTAAGTTGTTTTGGGAACTTATTAGGGAGTTTTACTGTTTTAGGGAGAGGACACTCGTTGACTTTC
GAGAACATACGGACTTCTACAAATGGAGCTGCACTAAGTGACAGCGCTAATAGCGGGTTATTTACTATTGAGGGTTTTAAAGAATTATCTTTTTCCAATT
GCAACTCATTACTTGCCGTACTGCCTGCTGCAACGACTAATAATGGTAGCCAGACTCCGACGACAACATCTACACCGTCTAATGGTACTATTTATTCTAA
AACAGATCTTTTGTTACTCAATAATGAGAAGTTCTCATTCTATAGTAATTTAGTCTCTGGAGATGGGGGAGCTATAGATGCTAAGAGCTTAACGGTTCAA
GGAATTAGCAAGCTTTGTGTCTTCCAAGAAAATACTGCTCAAGCTGATGGGGGAGCTTGTCAAGTAGTCACCAGTTTCTCTGCTATGGCTAACGAGGCTC
CTATTGCCTTTATAGCGAATGTTGCAGGAGTAAGAGGGGGAGGGATTGCTGCTGTTCAGGATGGGCAGCAGGGAGTGTCATCATCTACTTCAACAGAAGA
TCCAGTAGTAAGTTTTTCCAGAAATACTGCGGTAGAGTTTGATGGGAACGTAGCCCGAGTAGGAGGAGGGATTTACTCCTACGGGAACGTTGCTTTCCTG
AATAATGGAAAAACCTTGTTTCTCAACAATGTTGCTTCTCCTGTTTACATTGCTGCTGAGCAACCAACAAATGGACAGGCTTCTAATACGAGTGATAATT
ACGGAGATGGAGGAGCTATCTTCTGTAAGAATGGTGCGCAAGCAGCAGGATCCAATAACTCTGGATCAGTTTCCTTTGATGGAGAGGGAGTAGTTTTCTT
TAGTAGCAATGTAGCTGCTGGGAAAGGGGGAGCTATTTATGCCAAAAAGCTCTCGGTTGCTAACTGTGGCCCTGTACAATTCTTAGGGAATATCGCTAAT
GATGGTGGAGCGATTTATTTAGGAGAATCTGGAGAGCTCAGTTTATCTGCTGATTATGGAGATATTATTTTCGATGGGAATCTTAAAAGAACAGCCAAAG
AGAATGCTGCCGATGTTAATGGCGTAACTGTGTCCTCACAAGCCATTTCGATGGGATCGGGAGGGAAAATAACGACATTAAGAGCTAAAGCAGGGCATCA
GATTCTCTTTAATGATCCCATCGAGATGGCAAACGGAAATAACCAGCCAGCGCAGTCTTCCGAACCTCTAAAAATTAACGATGGTGAAGGATACACAGGG
GATATTGTTTTTGCTAATGGAAACAGTACTTTGTACCAAAATGTTACGATAGAGCAAGGAAGGATTGTTCTTCGTGAAAAGGCAAAATTATCAGTGAATT
CTCTAAGTCAGACAGGTGGGAGTCTGTATATGGAAGCTGGGAGTACATTGGATTTTGTAACTCCACAACCACCACAACAGCCTCCTGCCGCTAATCAGTT
GATCACGCTTTCCAATCTGCATTTGTCTCTTTCTTCTTTGTTAGCAAACAATGCAGTTACGAATCCTCCTACCAATCCTCCAGCGCAAGATTCTCATCCT
GCAATCATTGGTAGCACAACTGCTGGTTCTGTTACAATTAGTGGGCCTATCTTTTTTGAGGATTTGGATGATACAGCTTATGATAGGTATGATTGGCTAG
GTTCTAATCAAAAAATCGATGTCCTGAAATTACAGTTAGGGACTCAGCCCTCAGCTAATGCCCCATCAGATTTGACTCTAGGGAATGAGATGCCTAAGTA
TGGCTATCAAGGAAGCTGGAAGCTTGCGTGGGATCCTAATACAGCAAATAATGGTCCTTATACTCTGAAAGCTACATGGACTAAAACTGGGTATAATCCT
GGGCCTGAGCGAGTAGCTTCTTTGGTTCCAAATAGTTTATGGGGATCCATTTTAGATATACGATCTGCGCATTCAGCAATTCAAGCAAGTGTGGATGGGC
GCTCTTATTGTCGAGGATTATGGGTTTCTGGAGTTTCGAATTTCTTCTATCATGACCGCGATGCTTTAGGTCAGGGATATCGGTATATTAGTGGGGGTTA
TTCCTTAGGAGCAAACTCCTACTTTGGATCATCGATGTTTGGTCTAGCATTTACCGAAGTATTTGGTAGATCTAAAGATTATGTAGTGTGTCGTTCCAAT
CATCATGCTTGCATAGGATCCGTTTATCTATCTACCAAACAAGCTTTATGTGGATCCTATTTGTTCGGAGATGCGTTTATCCGTGCTAGCTACGGGTTTG
GGAACCAGCATATGAAAACCTCATACACATTTGCAGAGGAGAGCGATGTTCGTTGGGATAATAACTGTCTGGTTGGAGAGATTGGAGTGGGATTACCGAT
TGTGATTACTCCATCTAAGCTCTATTTGAATGAGTTGCGTCCTTTCGTGCAAGCTGAGTTTTCTTATGCCGATCATGAATCTTTTACAGAGGAAGGCGAT
CAAGCTCGGGCATTCAGGAGTGGACATCTCATGAATCTATCAGTTCCTGTTGGAGTAAAATTTGATCGATGTTCTAGTACACACCCTAATAAATATAGCT
TTATGGGGGCTTATATCTGTGATGCTTATCGCACCATCTCTGGGACTCAGACAACACTCCTATCCCATCAAGAGACATGGACAACAGATGCCTTTCATTT
GGCAAGACATGGAGTCATAGTTAGAGGGTCTATGTATGCTTCTCTAACAAGCAATATAGAAGTATATGGCCATGGAAGATATGAGTATCGAGATACTTCT
CGAGGTTATGGTTTGAGTGCAGGAAGTAAAGTCCGGTTCTAA
SEQ ID 83:
MQTSFHKFFLSMILAYSCCSLSGGGYAAEIMIPQGIYDGETLTVSFPYTVIGDPSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLTF
ENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATTNNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAIDAKSLTVQ
GISKLCVFQENTAQADGGACQVVTSFSAMANEAPIAFIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFDGNVARVGGGIYSYGNVAFL
NNGKTLFLNNVASPVYIAAEQPTNGQASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSSNVAAGKGGAIYAKKLSVANCGPVQFLGNIAN
DGGAIYLGESGELSLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKITTLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTG
DIVFANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGSTLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPPAQDSHP
AIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKIDVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTANNGPYTLKATWTKTGYNP
GPERVASLVPNSLWGSILDIRSAHSAIQASVDGRSYCRGLWVSGVSNFFYHDRDALGQGYRYISGGYSLGANSYFGSSMFGLAFTEVFGRSKDYVVCRSN
HHACIGSVYLSTKQALCGSYLFGDAFIRASYGFGNQHMKTSYTFAEESDVRWDNNCLVGEIGVGLPIVITPSKLYLNELRPFVQAEFSYADHESFTEEGD
QARAFRSGHLMNLSVPVGVKFDRCSSTHPNKYSFMGAYICDAYRTISGTQTTLLSHQETWTTDAFHLARHGVIVRGSMYASLTSNIEVYGHGRYEYRDTS
RGYGLSAGSKVRF
SEQ ID 84:
ATGCAAACGTCTTTCCATAAGTTCTTTCTTTCAATGATTCTAGCTTATTCTTGCTGCTCTTTAAGTGGGGGGGGGTATGCAGCAGAAATCATGATTCCTC
AAGGAATTTACGATGGGGAGACGTTAACTGTATCATTTCCCTATACTGTTATAGGAGATCCGAGTGGGACTACTGTTTTTTCTGCAGGAGAGTTAACGTT
AAAAAATCTTGACAATTCTATTGCAGCTTTGCCTTTAAGTTGTTTTGGGAACTTATTAGGGAGTTTTACTGTTTTAGGGAGAGGACACTCGTTGACTTTC
GAGAACATACGGACTTCTACAAATGGAGCTGCACTAAGTGACAGCGCTAATAGCGGGTTATTTACTATTGAGGGTTTTAAAGAATTATCTTTTTCCAATT
GCAACTCATTACTTGCCGTACTGCCTGCTGCAACGACTAATAATGGTAGCCAGACTCCGACGACAACATCTACACCGTCTAATGGTACTATTTATTCTAA
AACAGATCTTTTGTTACTCAATAATGAGAAGTTCTCATTCTATAGTAATTTAGTCTCTGGAGATGGGGGAGCTATAGATGCTAAGAGCTTAACGGTTCAA
GGAATTAGCAAGCTTTGTGTCTTCCAAGAAAATACTGCTCAAGCTGATGGGGGAGCTTGTCAAGTAGTCACCAGTTTCTCTGCTATGGCTAACGAGGCTC
CTATTGCCTTTATAGCGAATGTTGCAGGAGTAAGAGGGGGAGGGATTGCTGCTGTTCAGGATGGGCAGCAGGGAGTGTCATCATCTACTTCAACAGAAGA
TCCAGTAGTAAGTTTTTCCAGAAATACTGCGGTAGAGTTTGATGGGAACGTAGCCCGAGTAGGAGGAGGGATTTACTCCTACGGGAACGTTGCTTTCCTG
AATAATGGAAAAACCTTGTTTCTCAACAATGTTGCTTCTCCTGTTTACATTGCTGCTGAGCAACCAACAAATGGACAGGCTTCTAATACGAGTGATAATT
ACGGAGATGGAGGAGCTATCTTCTGTAAGAATGGTGCGCAAGCAGCAGGATCCAATAACTCTGGATCAGTTTCCTTTGATGGAGAGGGAGTAGTTTTCTT
TAGTAGCAATGTAGCTGCTGGGAAAGGGGGAGCTATTTATGCCAAAAAGCTCTCGGTTGCTAACTGTGGCCCTGTACAATTCTTAGGGAATATCGCTAAT
GATGGTGGAGCGATTTATTTAGGAGAATCTGGAGAGCTCAGTTTATCTGCTGATTATGGAGATATTATTTTCGATGGGAATCTTAAAAGAACAGCCAAAG
AGAATGCTGCCGATGTTAATGGCGTAACTGTGTCCTCACAAGCCATTTCGATGGGATCGGGAGGGAAAATAACGACATTAAGAGCTAAAGCAGGGCATCA
GATTCTCTTTAATGATCCCATCGAGATGGCAAACGGAAATAACCAGCCAGCGCAGTCTTCCGAACCTCTAAAAATTAACGATGGTGAAGGATACACAGGG
GATATTGTTTTTGCTAATGGAAACAGTACTTTGTACCAAAATGTTACGATAGAGCAAGGAAGGATTGTTCTTCGTGAAAAGGCAAAATTATCAGTGAATT
CTCTAAGTCAGACAGGTGGGAGTCTGTATATGGAAGCTGGGAGTACATTGGATTTTGTAACTCCACAACCACCACAACAGCCTCCTGCCGCTAATCAGTT
GATCACGCTTTCCAATCTGCATTTGTCTCTTTCTTCTTTGTTAGCAAACAATGCAGTTACGAATCCTCCTACCAATCCTCCAGCGCAAGATTCTCATCCT
GCAATCATTGGTAGCACAACTGCTGGTTCTGTTACAATTAGTGGGCCTATCTTTTTTGAGGATTTGGATGATACAGCTTATGATAGGTATGATTGGCTAG
GTTCTAATCAAAAAATCGATGTCCTGAAATTACAGTTAGGGACTCAGCCCTCAGCTAATGCCCCATCAGATTTGACTCTAGGGAATGAGATGCCTAAGTA
TGGCTATCAAGGAAGCTGGAAGCTTGCGTGGGATCCTAATACAGCAAATAATGGTCCTTATACTCTGAAAGCTACATGGACTAAAACTGGGTATAATCCT
GGGCCTGAGCGAGTAGCTTCTTTGGTTCCAAATAGTTTATGGGGATCCATTTTAGATATACGATCTGCGCATTCAGCAATTCAAGCAAGTGTGGATGGGC
GCTCTTATTGTCGAGGATTATGGGTTTCTGGAGTTTCGAATTTCTTCTATCATGACCGCGATGCTTTAGGTCAGGGATATCGGTATATTAGTGGGGGTTA
TTCCTTAGGAGCAAACTCCTACTTTGGATCATCGATGTTTGGTCTAGCATTTACCGAAGTATTTGGTAGATCTAAAGATTATGTAGTGTGTCGTTCCAAT
CATCATGCTTGCATAGGATCCGTTTATCTATCTACCAAACAAGCTTTATGTGGATCCTATTTGTTCGGAGATGCGTTTATCCGTGCTAGCTACGGGTTTG
GGAACCAGCATATGAAAACCTCATACACATTTGCAGAGGAGAGCGATGTTCGTTGGGATAATAACTGTCTGGTTGGAGAGATTGGAGTGGGATTACCGAT
TGTGATTACTCCATCTAAGCTCTATTTGAATGAGTTGCGTCCTTTCGTGCAAGCTGAGTTTTCTTATGCCGATCATGAATCTTTTACAGAGGAAGGCGAT
CAAGCTCGGGCATTCAGGAGTGGACATCTCATGAATCTATCAGTTCCTGTTGGAGTAAAATTTGATCGATGTTCTAGTACACACCCTAATAAATATAGCT
TTATGGGGGCTTATATCTGTGATGCTTATCGCACCATCTCTGGGACTCAGACAACACTCCTATCCCATCAAGAGACATGGACAACAGATGCCTTTCATTT
GGCAAGACATGGAGTCATAGTTAGAGGGTCTATGTATGCTTCTCTAACAAGCAATATAGAAGTATATGGCCATGGAAGATATGAGTATCGAGATACTTCT
CGAGGTTATGGTTTGAGTGCAGGAAGTAAAGTCCGGTTCTAA
SEQ ID 85:
MRPDHMNFCCLCAAILSSTAVLFGQDPLGETALLTKNPNHVVCTFFEDCTMESLFPALCAHASQDDPLYVLGNSYCWFVSKLHITDPKEALFKEKGDLSI
QNFRFLSFTDCSSKESSPSIIHQKNGQLSLRNNGSMSFCRNHAEGSGGAISADAFSLQHNYLFTAFEENSSKGNGGAIQAQTFSLSRNVSPISFARNRAD
LNGGAICCSNLICSGNVNPLFFTGNSATNGGAICCISDLNTSEKGSLSLACNQETLFASNSAKEKGGAIYAKHMVLRYNGPVSFINNSAKIGGAIAIQSG
GSLSILAGEGSVLFQNNSQRTSDQGLVRNAIYLEKDAILSSLEARNGDILFFDPIVQESSSKESPLPSSLQASVTSPTPATASPLVIQTSANRSVIFSSE
RLSEEEKTPDNLTSQLQQPIELKSGRLVLKDRAVLSAPSLSQDPQALLLMEAGTSLKTSSDLKLATLSIPLHSLDTEKSVTIHAPNLSIQKIFLSNSGDE
NFYENVELLSKEQNNIPLLTLSKEQSHLHLPDGNLSSHFGYQGDWTFSWKDSDEGHSLIANWTPKNYVPHPERQSTLVANTLWNTYSDMQAVQSMINTIA
HGGAYLFGTWGSAVSNLFYAHDSSGKPIDNWHHRSLGYLFGISTHSLDDHSFCLAAGQLLGKSSDSFITSTETTSYIATVQAQLATPLMKISAQACYNES
IHELKTKYRSFSKEGFGSWHSVAVSGEVCASIPIVSNGSGLFSSFSIFSKLQGFSGTQDGFEESSGEIRSFSASSFRNISLPMGITFEKKSQKTRNYYYF
LGAYIQDLKRDVESGPVVLLKNAVSWDAPMANLDSRAYMFRLTNQRALHRLQTLLNVSYVLRGQSHSYSLDLGTTYRF
SEQ ID 86:
ATGCGACCTGATCATATGAACTTCTGTTGTCTATGTGCTGCTATTTTGTCATCCACAGCGGTCCTCTTTGGCCAGGATCCCTTAGGTGAAACCGCCCTCC
TCACTAAAAATCCTAATCATGTCGTCTGTACATTTTTTGAGGACTGTACCATGGAGAGCCTCTTTCCTGCTCTTTGTGCTCATGCATCACAAGATGATCC
TTTGTATGTACTTGGAAATTCCTACTGTTGGTTCGTATCTAAACTCCATATCACGGACCCCAAAGAGGCTCTTTTTAAAGAAAAAGGAGATCTTTCCATT
CAAAATTTTCGCTTCCTTTCCTTCACAGATTGCTCTTCCAAGGAAAGCTCTCCTTCTATTATTCATCAAAAGAATGGTCAGTTATCCTTGCGCAATAATG
GTAGCATGAGTTTCTGTCGAAATCATGCTGAAGGCTCTGGAGGAGCCATCTCTGCGGATGCCTTTTCTCTACAACACAACTATCTTTTCACAGCTTTTGA
AGAGAATTCTTCTAAAGGAAATGGCGGAGCCATTCAGGCTCAAACCTTCTCTTTATCTAGAAATGTGTCGCCTATTTCTTTCGCCCGTAATCGTGCGGAT
TTAAATGGCGGCGCTATTTGCTGTAGTAATCTTATTTGTTGAGGGAATGTAAACCCTCTCTTTTTCACTGGAAACTCCGCCACGAATGGAGGCGCTATTT
GTTGTATCAGCGATCTAAACACCTCAGAAAAAGGCTCTCTCTCTCTTGCTTGTAACCAAGAAACGCTATTTGCAAGCAATTCTGCTAAAGAAAAAGGCGG
GGCTATTTATGCCAAGCACATGGTATTGCGTTATAACGGTCCTGTTTCCTTCATTAACAACAGCGCTAAAATAGGTGGAGCTATCGCCATCCAGTCCGGA
GGGAGTCTCTCTATCCTTGCAGGTGAAGGATCTGTTCTGTTCCAGAATAACTCCCAACGCACCTCCGACCAAGGTCTAGTAAGAAACGCCATCTACTTAG
AGAAAGATGCGATTCTTTCTTCCTTAGAAGCTCGCAACGGAGATATTCTTTTCTTTGATCCTATTGTACAAGAAAGTAGCAGCAAAGAATCGCCTCTTCC
CTCCTCTTTGCAAGCCAGCGTGACTTCTCCCACCCCAGCCACCGCATCTCCTTTAGTTATTCAGACAAGTGCAAACCGTTGAGTGATTTTCTCGAGCGAA
CGTCTTTCTGAAGAAGAAAAAACTCCTGATAACCTCACTTCCCAACTACAGGAGCCTATCGAACTGAAATCCGGACGCTTAGTTTTAAAAGATCGCGCTG
TCCTTTCCGCGCCTTCTCTCTCTCAGGATCCTCAAGCTCTCCTCATTATGGAAGCGGGAACTTCTTTAAAAACTTCCTCTGATTTGAAGTTAGCTACGCT
AAGTATTCCCCTTCATTCCTTAGATACTGAAAAAAGCGTAACTATCCACGCCCCTAACCTTTCTATCCAAAAGATCTTCCTCTCTAATTCTGGAGATGAG
AATTTTTATGAAAATGTAGAGCTTCTCAGTAAAGAGCAAAACAATATTCCTGTCCTTACTCTCTCTAAAGAGCAATCTCATTTACATCTTCCTGATGGGA
ACCTCTCTTCTCACTTTGGATATCAAGGAGATTGGACTTTTTCTTGGAAAGATTCTGATGAAGGGCATTCTCTGATTGCTAATTGGACGCCTAAAAACTA
TGTGCCTCATCCAGAACGTCAATCTACACTCGTTGCGAACACTCTTTGGAACACCTATTCCGATATGCAAGCTGTGCAGTCGATGATTAATACAATAGCG
CACGGAGGAGCCTATCTATTTGGAACGTGGGGATCTGCTGTTTCTAATTTATTCTATGCTCACGACAGCTCTGGGAAACCTATCGATAATTGGCATCATA
GAAGCCTTGGCTACCTATTCGGTATCAGTACTCACAGTTTAGATGACCATTCTTTCTGCTTGGCTGCAGGACAATTACTCGGGAAATCGTCCGATTCCTT
TATTACGTCTACAGAAACGACCTCCTATATAGCTACTGTACAAGCGCAACTCGCTACCCCTCTAATGAAAATCTCTGCACAGGCATGCTATAATGAAAGT
ATCCATGAGCTAAAAACAAAATATCGCTCCTTCTCTAAAGAAGGATTCGGATCCTGGCATAGCGTTGCAGTATCCGGAGAAGTGTGCGCATCGATTCCTA
TTGTATCCAATGGTTCCGGACTGTTCAGCTCCTTCTCTATTTTCTCTAAACTGCAAGGATTTTCAGGAACACAGGACGGTTTTGAGGAGAGTTCGGGAGA
GATTCGGTCCTTTTCTGCCAGCTCTTTCAGAAATATTTCACTTCCTATGGGAATAACATTTGAAAAAAAATCCCAAAAAACACGAAACTACTATTACTTT
CTGGGAGCCTACATCCAAGACCTAAAACGTGATGTGGAATCGGGACCTGTAGTGTTACTCAAAAATGCCGTCTCCTGGGATGCTCCTATGGCGAACTTGG
ATTCGCGAGCCTACATGTTCAGGCTTACGAATCAAAGAGCTCTGCATAGACTTCAGACGCTGTTAAATGTGTCTTACGTAGTGCGCGGGCAAAGCCATAG
TTACTCCCTGGATCTGGGGACCACTTACAGGTTCTAG
SEQ ID 87:
MRPDHMNFCCLCAAILSSTAVLFGQDPLGETALLTKNPNHVVCTFFEDCTMESLFPALCAHASQDDPLYVLGNSYCWFVSKLHITDPKEALFKEKGDLSI
QNFRFLSFTDCSSKESSPSIIHQKNGQLSLRNNGSMSFCRNHAEGSGGAISADAFSLQHNYLFTAFEENSSKGNGGAIQAQTFSLSRNVSPISFARNRAD
LNGGAICCSNLICSGNVNPLFFTGNSATNGGAICCISDLNTSEKGSLSLACNQETLFASNSAKEKGGAIYAKHMVLRYNGPVSFINNSAKIGGAIAIQSG
GSLSIIAGEGSVLFQNNSQRTSDQGLVRNAIYLEKDAILSSLEARNGDILPFDPIVQESSSKESPLPSSLQASVTSPTPATASPLVIQTSANRSVIFSSE
RLSEEEKTPDNLTSQLQQPIELKSGRLVLKDRAVLSAPSLSQDPQALLIMEAGTSLKTSSDLKLATLSIPLHSLDTEKSVTIHAPNLSIQKIFLSNSGDE
NFYENVELLSKEQNNIPLLTLSKEQSHLHLPDGNLSSHFGYQGDWTFSWKDSDEGHSLIANWTPKNYVPHPERQSTLVANTLWNTYSDMQAVQSMINTIA
HGGAYLFGTWGSAVSNLFYAHDSSGKPIDNWHHRSLGYLFGISTHSLDDHSFCLAAGQLLGKSSDSFITSTETTSYIATVQAQLATPLMKISAQACYNES
IHELKTKYRSFSKEGFGSWHSVAVSGEVCASIPIVSNGSGLFSSFSIFSKLQGFSGTQDGFEESSGEIRSFSASSFRNISLPMGITFEKKSQKTRNYYYF
LGAYIQDLKRDVESGPVVLLKNAVSWDAPMANLDSRAYMFRLTNQRALHRLQTLLNVSYVLRGQSHSYSLDLGTTYRF
SEQ ID 88:
ATGCGACCTGATCATATGAACTTCTGTTGTCTATGTGCTGCTATTTTGTCATCCACAGCGGTCCTCTTTGGCCAGGATCCCTTAGGTGAAACCGCCCTCC
TCACTAAAAATCCTAATCATGTCGTCTGTACATTTTTTGAGGACTGTACCATGGAGAGCCTCTTTCCTGCTCTTTGTGCTCATGCATCACAAGATGATCC
TTTGTATGTACTTGGAAATTCCTAGTGTTGGTTCGTATCTAAACTCCATATCACGGACCCCAAAGAGGCTCTTTTTAAAGAAAAAGGAGATCTTTCCATT
CAAAATTTTCGCTTCCTTTCCTTCACAGATTGCTCTTCCAAGGAAAGCTCTCCTTCTATTATTCATCAAAAGAATGGTCAGTTATCCTTGCGCAATAATG
GTAGCATGAGTTTCTGTCGAAATCATGCTGAAGGCTCTGGAGGAGCCATCTCTGCGGATGCCTTTTCTCTACAACACAACTATCTTTTCACAGCTTTTGA
AGAGAATTCTTCTAAAGGAAATGGCGGAGCCATTCAGGCTCAAACCTTCTCTTTATCTAGAAATGTGTCGCCTATTTCTTTCGCCCGTAATCGTGCGGAT
TTAAATGGCGGCGCTATTTGCTGTAGTAATCTTATTTGTTCAGGGAATGTAAACCCTCTCTTTTTCACTGGAAACTCCGCCACGAATGGAGGCGCTATTT
GTTGTATCAGCGATCTAAACACCTCAGAAAAAGGCTCTCTCTCTCTTGCTTGTAACCAAGAAACGCTATTTGCAAGCAATTCTGCTAAAGAAAAAGGCGG
GGCTATTTATGCCAAGCACATGGTATTGCGTTATAACGGTCCTGTTTCCTTCATTAACAACAGCGCTAAAATAGGTGGAGCTATCGCCATCCAGTCCGGA
GGGAGTCTCTCTATCCTTGCAGGTGAAGGATCTGTTCTGTTCCAGAATAACTCCCAACGCACCTCCGACCAAGGTCTAGTAAGAAACGCCATCTACTTAG
AGAAAGATGCGATTCTTTCTTCCTTAGAAGCTCGCAACGGAGATATTCTTTTCTTTGATCCTATTGTACAAGAAAGTAGCAGCAAAGAATCGCCTCTTCC
CTCCTCTTTGCAAGCCAGCGTGACTTCTCCCACCCCAGCCACCGCATCTCCTTTAGTTATTCAGACAAGTGCAAACCGTTCAGTGATTTTCTCGAGCGAA
CGTCTTTCTGAAGAAGAAAAAACTCCTGATAACCTCACTTCCCAACTACAGCAGCCTATCGAACTGAAATCCGGACGCTTAGTTTTAAAAGATCGCGCTG
TCCTTTCCGCGCCTTCTCTCTCTCAGGATCCTCAAGCTCTCCTCATTATGGAAGCGGGAACTTCTTTAAAAACTTCCTCTGATTTGAAGTTAGCTACGCT
AAGTATTCCCCTTCATTCCTTAGATACTGAAAAAAGCGTAACTATCCACGCCCCTAACCTTTCTATCCAAAAGATCTTCCTCTCTAATTCTGGAGATGAG
AATTTTTATGAAAATGTAGAGCTTCTCAGTAAAGAGCAAAACAATATTCCTCTCCTTACTCTCTCTAAAGAGCAATCTCATTTACATCTTCCTGATGGGA
ACCTCTCTTCTCACTTTGGATATCAAGGAGATTGGACTTTTTCTTGGAAAGATTCTGATGAAGGGCATTCTCTGATTGCTAATTGGACGCCTAAAAACTA
TGTGCCTCATCCAGAACGTCAATCTACACTCGTTGCGAACACTCTTTGGAACACCTATTCCGATATGCAAGCTGTGCAGTCGATGATTAATACAATAGCG
CACGGAGGAGCCTATCTATTTGGAACGTGGGGATCTGCTGTTTCTAATTTATTCTATGCTCACGACAGCTCTGGGAAACCTATCGATAATTGGCATCATA
GAAGCCTTGGCTACCTATTCGGTATCAGTACTCACAGTTTAGATGACCATTCTTTCTGCTTGGCTGCAGGACAATTACTCGGGAAATCGTCCGATTCCTT
TATTACGTCTACAGAAACGACCTCCTATATAGCTACTGTACAAGCGCAACTCGCTACCCCTCTAATGAAAATCTCTGCACAGGCATGCTATAATGAAAGT
ATCCATGAGCTAAAAACAAAATATCGCTCCTTCTCTAAAGAAGGATTCGGATCCTGGCATAGCGTTGCAGTATCCGGAGAAGTGTGCGCATCGATTCCTA
TTGTATCCAATGGTTCCGGACTGTTCAGCTCCTTCTCTATTTTCTCTAAACTGCAAGGATTTTCAGGAACACAGGACGGTTTTGAGGAGAGTTCGGGAGA
GATTCGGTCCTTTTCTGCCAGCTCTTTCAGAAATATTTCACTTCCTATGGGAATAACATTTGAAAAAAAATCCCAAAAAACACGAAACTACTATTACTTT
CTGGGAGCCTACATCCAAGACCTAAAACGTGATGTGGAATCGGGACCTGTAGTGTTACTCAAAAATGCCGTCTCCTGGGATGCTCCTATGGCGAACTTGG
ATTCGCGAGCCTACATGTTCAGGCTTACGAATCAAAGAGCTCTGCATAGACTTCAGACGCTGTTAAATGTGTCTTACGTACTGCGCGGGCAAAGCCATAG
TTACTCCCTGGATCTGGGGACCACTTACAGGTTCTAG
SEQ ID 89:
MNRVIEIHAHYDQRQLSQSPNTNFLVHHPYLTLIPKFLLGALIVYAPYSFAEMELAISGHKQGKDRDTFTMISSCPEGTNYIINRKLILSDFSLLNKVSS
GGAFRNLAGKISFLGKNSSASIHFKHININGFGAGVFSESSIEFTDLRKLVAFGSESTGGIFTAKEDISFKNNHHIAFRNNITKGNGGVIQLQGDMKGSV
SFVDQRGAIIFTNNQAVTSSSMKHSGRGGAISGDFAGSRILFLNNQQITFEGNSAVHGGAIYNKNGLVEFLGNAGPLAFKENTTIANGGAIYTSNFKANQ
QTSPILFSQNHANKKGGAIYAQYVNLEQNQDTIRFEKNTAKEGGGAITSSQCSITAHNTIIFSDNAAGDLGGGAILLEGKKPSLTLIAHSGNIAFSGNTM
LHITKKASLDRHNSILIKEAPYKIQIAANKNHSIHFFDPVMALSASSSPIQINAPEYETPFFSPKGMIVFSGANLLDDAREDVANRTSIFNQPVHLYNGT
LSIENGAHLIVQSFKQTGGRISLSPGSSLALYTMNSFFHGNISSKEPLEINGLSFGVDISPSNLQAEIRAGNAPLRLSGSPSIHDPEGLFYENRDTAASP
YQMEILLTSDKIVDISKFTTDSLVTNKQSGFQGAWHFSWQPNTINNTKQKILRASWLPTGEYVLESNRVGRAVPNSLWSTFLLLQTASHNLGDHLCNNRS
LIPTSYFGVLIGGTGAEMSTHSSEEESFISRLGATGTSIIRLTPSLTLSGGGSHMFGDSFVADLPEHITSEGIVQNVGLTHVWGPLTVNSTLCAALDHNA
MVRICSKKDHTYGKWDTFGMRGTLGASYTFLEYDQTMRVFSFANIEATNILQRAFTETGYNPRSFSKTKLLNIAIPIGIGYEFCLGNSSFALLGKGSIGY
SRDIKRENPSTLAHLAMNDFAWTTNGCSVPTSAHTLANQLILRYKACSLYITAYTINREGKNLSNSLSCGGYVGF
SEQ ID 90:
ATGAATCGAGTTATAGAAATCCATGCTCACTACGATCAAAGACAACTTTCTCAATCTCCAAATACAAACTTCTTAGTACATCATCCTTATCTTACTCTTA
TTCCCAAGTTTCTACTAGGAGCTCTAATCGTCTATGCTCCTTATTCGTTTGCAGAAATGGAATTAGCTATTTCTGGACATAAACAAGGTAAAGATCGAGA
TACCTTTACCATGATCTCTTCCTGTCCTGAAGGCACTAATTACATCATCAATCGCAAACTCATACTCAGTGATTTCTCGTTACTAAATAAAGTTTCATCA
GGGGGAGCCTTTCGGAATCTAGCAGGGAAAATTTCCTTCTTAGGAAAAAATTCTTCTGCGTCCATTCATTTTAAACACATTAATATCAATGGTTTTGGAG
CCGGAGTCTTTTCTGAATCCTCTATTGAATTTACTGATTTACGAAAACTTGTTGCTTTTGGATCTGAAAGCACAGGAGGAATTTTTACTGCGAAAGAGGA
CATCTCTTTTAAAAACAACCACCACATTGCCTTCCGCAATAATATCACCAAAGGGAATGGTGGCGTTATCCAGCTCCAAGGAGATATGAAAGGAAGCGTA
TCCTTTGTAGATCAACGTGGAGCTATCATCTTTACCAATAACCAAGCTGTAACTTCTTCATCAATGAAACATAGTGGTCGTGGAGGAGCAATTAGCGGTG
ACTTCGCAGGATCCAGAATTCTTTTTCTTAATAACCAACAAATTACTTTCGAAGGCAATAGCGCTGTGCATGGAGGTGCTATCTACAATAAGAATGGCCT
TGTCGAGTTCTTAGGAAATGCAGGACCTCTTGCCTTTAAAGAGAACACAACAATAGCTAACGGGGGAGCTATATACACAAGTAATTTCAAAGCGAATCAA
CAAACATCCCCCATTCTATTCTCTCAAAATCATGCGAATAAGAAAGGCGGAGCGATTTACGCGCAATATGTGAACTTAGAACAGAATCAAGATACTATTC
GCTTTGAAAAAAATACCGCTAAAGAAGGCGGTGGAGCCATCACCTCTTCTCAATGCTCAATTACTGCTCATAATACCATCATTTTTTCCGATAATGCTGC
CGGAGATCTTGGAGGAGGAGCAATTCTTCTAGAAGGGAAAAAACCTTCTCTAACCTTGATTGCTCATAGTGGTAATATTGCATTTAGCGGCAATACCATG
CTTCATATCACCAAAAAAGCTTCCCTAGATCGACACAATTCTATCTTAATCAAAGAAGCTCCCTATAAAATCCAACTTGCAGCGAACAAAAACCATTCTA
TTCATTTCTTTGATCCTGTCATGGCATTGTCAGCATCATCTTCCCCTATACAAATCAATGCTCCTGAGTATGAAACTCCCTTCTTCTCACCTAAGGGTAT
GATCGTTTTCTCGGGTGCGAATCTTTTAGATGATGCTAGGGAAGATGTTGCAAATAGAACATCGATTTTTAACCAACCCGTTCATCTATATAATGGCACC
CTATCTATCGAAAATGGAGCCCATCTGATTGTCCAAAGCTTCAAACAGACCGGAGGACGTATCAGTTTATCTCCAGGATCCTCCTTGGCTCTATACACGA
TGAACTCGTTCTTCCATGGCAACATATCCAGCAAAGAACCCCTAGAAATTAATGGTTTAAGCTTTGGAGTAGATATCTCTCCTTCTAATCTTCAAGCAGA
GATCCGTGCCGGCAACGCTCCTTTACGATTATCCGGATCCCCATCTATCCATGATCCTGAAGGATTATTCTACGAAAATCGCGATACTGCAGCATCACCA
TACCAAATGGAAATCTTGCTCACCTCTGATAAAATTGTAGATATCTCCAAATTTACTACTGATTCTCTAGTTACGAACAAACAATCAGGATTCCAAGGAG
CCTGGCATTTTAGCTGGCAGCCAAATACTATAAACAATACTAAACAAAAAATATTAAGAGCTTCTTGGCTCCCAACAGGAGAATATGTCCTTGAATCCAA
TCGAGTGGGGCGTGCCGTTCCTAATTCCTTATGGAGCACATTTTTACTTTTACAGACAGCCTCTCATAACTTAGGCGATCATCTATGTAATAATCGATCT
CTTATTCCTACTTCATACTTCGGAGTTTTAATTGGAGGAACTGGAGCAGAAATGTCTACCCACTCCTCAGAAGAAGAAAGCTTTATATCTCGTTTAGGAG
CTACAGGAACCTCTATCATACGCTTAACTCCCTCCCTGACACTCTCTGGAGGAGGCTCACATATGTTCGGAGATTCGTTCGTTGCAGACTTACCAGAACA
CATCACTTCAGAAGGAATTGTTCAGAATGTCGGTTTAACCCATGTCTGGGGACCCCTTACTGTCAATTCTACATTATGTGCAGCCTTAGATCACAACGCG
ATGGTCCGCATATGCTCCAAAAAAGATCACACCTATGGGAAATGGGATACATTCGGTATGCGAGGAACATTAGGAGCCTCTTATACATTCCTAGAATATG
ATCAAACTATGCGCGTATTCTCATTCGCCAACATCGAAGCCACAAATATCTTGCAAAGAGCTTTTACTGAAACAGGCTATAACCCAAGAAGTTTTTCCAA
GACAAAACTTCTAAACATCGCCATCCCCATAGGGATTGGTTATGAATTCTGCTTAGGGAATAGCTCTTTTGCTCTACTAGGTAAGGGATCCATCGGTTAC
TCTCGAGATATTAAACGAGAAAACCCATCCACTCTTGCTCACCTGGCTATGAATGATTTTGCTTGGACTACCAATGGCTGTTCAGTTCCAACCTCTGCAC
ACACATTGGCAAATCAATTGATTCTTCGCTATAAAGCATGTTCCTTATACATCACGGCATATACTATCAACCGTGAAGGGAAGAACCTCTCCAATAGCTT
ATCCTGCGGAGGCTATGTTGGCTTCTAA
SEQ ID 91:
MNRVIEIHAHYDQRQLSQSPNTNFLVHHPYLTLIPKFLLGALIVYAPYSFAEMELAISGHKQGKDRDTFTMISSCPEGTNYIINRKLILSDFSLLNKVSS
GGAFRNLAGKISFLGKNSSASIHFKHININGFGAGVFSESSIEFTDLRKLVAFGSESTGGIFTAKEDISFKNNHHIAFRNNITKGNGGVIQLQGDMKGSV
SFVDQRGAIIFTNNQAVTSSSMKHSGRGGAISGDFAGSRILFLNNQQITFEGNSAVHGGAIYNKNGLVEFLGNAGPLAFKENTTIANGGAIYTSNFKANQ
QTSPILFSQNHANKKGGAIYAQYVNLEQNQDTIRFEKNTAKEGGGAITSSQCSITAHNTIIFSDNAAGDLGGGAILLEGKKPSLTLIAHSGNIAFSGNTM
LHITKKASLDRHNSILIKEAPYKIQLAANKNHSIHFFDPVMALSASSSPIQINAPEYETPFFSPKGMIVFSGANLLDDAREDVANRTSIFNQPVHLYNGT
LSIENGAHLIVQSFKQTGGRISLSPGSSLALYTMNSFFHGNISSKEPLEINGLSFGVDISPSNLQAEIRAGNAPLRLSGSPSIHDPEGLFYENRDTAASP
YQMEILLTSDKIVDISKFTTDSLVTNKQSGFQGAWHFSWQPNTINNTKQKILRASWLPTGEYVLESNRVGRAVPNSLWSTFLLLQTASHNLGDHLCNNRS
LIPTSYFGVLIGGTGAEMSTHSSEEESFISRLGATGTSIIRLTPSLTLSGGGSHMFGDSFVADLPEHITSEGIVQNVGLTHVWGPLTVNSTLCAALDHNA
MVRICSKKDHTYGKWDTFGMRGTLGASYTFLEYDQTMRVFSFANIEATNILQRAFTETGYNPRSFSKTKLLNIAIPIGIGYEFCLGNSSFALLGKGSIGY
SRDIKRENPSTLAHLAMNDFAWTTNGCSVPTSAHTLANQLILRYKACSLYITAYTINREGKNLSNSLSCGGYVGF
SEQ ID 92:
ATGAATCGAGTTATAGAAATCCATGCTCACTACGATCAAAGACAACTTTCTCAATCTCCAAATACAAACTTCTTAGTACATCATCCTTATCTTACTCTTA
TTCCCAAGTTTCTACTAGGAGCTCTAATCGTCTATGCTCCTTATTCGTTTGCAGAAATGGAATTAGCTATTTCTGGACATAAACAAGGTAAAGATCGAGA
TACCTTTACCATGATCTCTTCCTGTCCTGAAGGCACTAATTACATCATCAATCGCAAACTCATACTCAGTGATTTCTCGTTACTAAATAAAGTTTCATCA
GGGGGAGCCTTTCGGAATCTAGCAGGGAAAATTTCCTTCTTAGGAAAAAATTCTTCTGCGTCCATTCATTTTAAACACATTAATATCAATGGTTTTGGAG
CCGGAGTCTTTTCTGAATCCTCTATTGAATTTACTGATTTACGAAAACTTGTTGCTTTTGGATCTGAAAGCACAGGAGGAATTTTTACTGCGAAAGAGGA
CATCTCTTTTAAAAACAACCACCACATTGCCTTCCGCAATAATATCACCAAAGGGAATGGTGGCGTTATCCAGCTCCAAGGAGATATGAAAGGAAGCGTA
TCCTTTGTAGATCAACGTGGAGCTATCATCTTTACCAATAACCAAGCTGTAACTTCTTCATCAATGAAACATAGTGGTCGTGGAGGAGCAATTAGCGGTG
ACTTCGCAGGATCCAGAATTCTTTTTCTTAATAACCAACAAATTACTTTCGAAGGCAATAGCGCTGTGCATGGAGGTGCTATCTACAATAAGAATGGCCT
TGTCGAGTTCTTAGGAAATGCAGGACCTCTTGCCTTTAAAGAGAACACAACAATAGCTAACGGGGGAGCTATATACACAAGTAATTTCAAAGCGAATCAA
CAAACATCCCCCATTCTATTCTCTCAAAATCATGCGAATAAGAAAGGCGGAGCGATTTACGCGCAATATGTGAACTTAGAACAGAATCAAGATACTATTC
GCTTTGAAAAAAATACCGCTAAAGAAGGCGGTGGAGCCATCACCTCTTCTCAATGCTCAATTACTGCTCATAATACCATCATTTTTTCCGATAATGCTGC
CGGAGATCTTGGAGGAGGAGCAATTCTTCTAGAAGGGAAAAAACCTTCTCTAACCTTGATTGCTCATAGTGGTAATATTGCATTTAGCGGCAATACCATG
CTTCATATCACCAAAAAAGCTTCCCTAGATCGACACAATTCTATCTTAATCAAAGAAGCTCCCTATAAAATCCAACTTGCAGCGAACAAAAACCATTCTA
TTCATTTCTTTGATCCTGTCATGGCATTGTCAGCATCATCTTCCCCTATACAAATCAATGCTCCTGAGTATGAAACTCCCTTCTTCTCACCTAAGGGTAT
GATCGTTTTCTCGGGTGCGAATCTTTTAGATGATGCTAGGGAAGATGTTGCAAATAGAACATCGATTTTTAACCAACCCGTTCATCTATATAATGGCACC
CTATCTATCGAAAATGGAGCCCATCTGATTGTCCAAAGCTTCAAACAGACCGGAGGACGTATCAGTTTATCTCCAGGATCCTCCTTGGCTCTATACACGA
TGAACTCGTTCTTCCATGGCAACATATCCAGCAAAGAACCCCTAGAAATTAATGGTTTAAGCTTTGGAGTAGATATCTCTCCTTCTAATCTTCAAGCAGA
GATCCGTGCCGGCAACGCTCCTTTACGATTATCCGGATCCCCATCTATCCATGATCCTGAAGGATTATTCTACGAAAATCGCGATACTGCAGCATCACCA
TACCAAATGGAAATCTTGCTCACCTCTGATAAAATTGTAGATATCTCCAAATTTACTACTGATTCTCTAGTTACGAACAAACAATCAGGATTCCAAGGAG
CCTGGCATTTTAGCTGGCAGCCAAATACTATAAACAATACTAAACAAAAAATATTAAGAGCTTCTTGGCTCCCAACAGGAGAATATGTCCTTGAATCCAA
TCGAGTGGGGCGTGCCGTTCCTAATTCCTTATGGAGCACATTTTTACTTTTACAGACAGCCTCTCATAACTTAGGCGATCATCTATGTAATAATCGATCT
CTTATTCCTACTTCATACTTCGGAGTTTTAATTGGAGGAACTGGAGCAGAAATGTCTACCCACTCCTCAGAAGAAGAAAGCTTTATATCTCGTTTAGGAG
CTACAGGAACCTCTATCATACGCTTAACTCCCTCCCTGACACTCTCTGGAGGAGGCTCACATATGTTCGGAGATTCGTTCGTTGCAGACTTACCAGAACA
CATCACTTCAGAAGGAATTGTTCAGAATGTCGGTTTAACCCATGTCTGGGGACCCCTTACTGTCAATTCTACATTATGTGCAGCCTTAGATCACAACGCG
ATGGTCCGCATATGCTCCAAAAAAGATCACACCTATGGGAAATGGGATACATTCGGTATGCGAGGAACATTAGGAGCCTCTTATACATTCCTAGAATATG
ATCAAACTATGCGCGTATTCTCATTCGCCAACATCGAAGCCACAAATATCTTGCAAAGAGCTTTTACTGAAACAGGCTATAACCCAAGAAGTTTTTCCAA
GACAAAACTTCTAAACATCGCCATCCCCATAGGGATTGGTTATGAATTCTGCTTAGGGAATAGCTCTTTTGCTCTACTAGGTAAGGGATCCATCGGTTAC
TCTCGAGATATTAAACGAGAAAACCCATCCACTCTTGCTCACCTGGCTATGAATGATTTTGCTTGGACTACCAATGGCTGTTCAGTTCCAACCTCTGCAC
ACACATTGGCAAATCAATTGATTCTTCGCTATAAAGCATGTTCCTTATACATCACGGCATATACTATCAACCGTGAAGGGAAGAACCTCTCCAATAGCTT
ATCCTGCGGAGGCTATGTTGGCTTCTAA
SEQ ID 93:
MQTSFHKFFLSMILAYSCCSLSGGGYAAEIMIPQGIYDGETLTVSFPYTVIGDPSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLTF
ENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATTNNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAIDAKSLTVQ
GISKLCVFQENTAQADGGACQVVTSFSAMANEAPIAFIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFDGNVARVGGGIYSYGNVAFL
NNGKTLFLNNVASPVYIAAEQPTNGQASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSSNVAAGKGGAIYAKKLSVANCGPVQFLGNIAN
DGGAIYLGESGELSLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKITTLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTG
DIVFANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGSTLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPPAQDSHP
AIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKIDVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTANNGPYTLKATWTKTGYNP
GPERVASLVPNSLWGSILDIRSAHSAIQASVDGRSYCRGLWVSGVSNFFYHDRDALGQGYRYISGGYSLGANSYFGSSMFGLAFTEVFGRSKDYVVCRSN
HHACIGSVYLSTKQALCGSYLFGDAFIRASYGFGNQHMKTSYTFAEESDVRWDNNCLVGEIGVGLPIVITPSKLYLNELRPFVQAEFSYADHESFTEEGD
QARAFRSGHLMNLSVPVGVKFDRCSSTHPNKYSFMGAYICDAYRTISGTQTTLLSHQETWTTDAFHLARHGVIVRGSMYASLTSNIEVYGHGRYEYRDTS
RGYGLSAGSKVRF
SEQ ID 94:
ATGCAAACGTCTTTCCATAAGTTCTTTCTTTCAATGATTCTAGCTTATTCTTGCTGCTCTTTAAGTGGGGGGGGGTATGCAGCAGAAATCATGATTCCTC
AAGGAATTTACGATGGGGAGACGTTAACTGTATCATTTCCCTATACTGTTATAGGAGATCCGAGTGGGACTACTGTTTTTTCTGCAGGAGAGTTAACGTT
AAAAAATCTTGACAATTCTATTGCAGCTTTGCCTTTAAGTTGTTTTGGGAACTTATTAGGGAGTTTTACTGTTTTAGGGAGAGGACACTCGTTGACTTTC
GAGAACATACGGACTTCTACAAATGGAGCTGCACTAAGTGACAGCGCTAATAGCGGGTTATTTACTATTGAGGGTTTTAAAGAATTATCTTTTTCCAATT
GCAACTCATTACTTGCCGTACTGCCTGCTGCAACGACTAATAATGGTAGCCAGACTCCGACGACAACATCTACACCGTCTAATGGTACTATTTATTCTAA
AACAGATCTTTTGTTACTCAATAATGAGAAGTTCTCATTCTATAGTAATTTAGTCTCTGGAGATGGGGGAGCTATAGATGCTAAGAGCTTAACGGTTCAA
GGAATTAGCAAGCTTTGTGTCTTCCAAGAAAATACTGCTCAAGCTGATGGGGGAGCTTGTCAAGTAGTCACCAGTTTCTCTGCTATGGCTAACGAGGCTC
CTATTGCCTTTATAGCGAATGTTGCAGGAGTAAGAGGGGGAGGGATTGCTGCTGTTCAGGATGGGCAGCAGGGAGTGTCATCATCTACTTCAACAGAAGA
TCCAGTAGTAAGTTTTTCCAGAAATACTGCGGTAGAGTTTGATGGGAACGTAGCCCGAGTAGGAGGAGGGATTTACTCCTACGGGAACGTTGCTTTCCTG
AATAATGGAAAAACCTTGTTTCTCAACAATGTTGCTTCTCCTGTTTACATTGCTGCTGAGCAACCAACAAATGGACAGGCTTCTAATACGAGTGATAATT
ACGGAGATGGAGGAGCTATCTTCTGTAAGAATGGTGCGCAAGCAGCAGGATCCAATAACTCTGGATCAGTTTCCTTTGATGGAGAGGGAGTAGTTTTCTT
TAGTAGCAATGTAGCTGCTGGGAAAGGGGGAGCTATTTATGCCAAAAAGCTCTCGGTTGCTAACTGTGGCCCTGTACAATTCTTAGGGAATATCGCTAAT
GATGGTGGAGCGATTTATTTAGGAGAATCTGGAGAGCTCAGTTTATCTGCTGATTATGGAGATATTATTTTCGATGGGAATCTTAAAAGAACAGCCAAAG
AGAATGCTGCCGATGTTAATGGCGTAACTGTGTCCTCACAAGCCATTTCGATGGGATCGGGAGGGAAAATAACGACATTAAGAGCTAAAGCAGGGCATCA
GATTCTCTTTAATGATCCCATCGAGATGGCAAACGGAAATAACCAGCCAGCGCAGTCTTCCGAACCTCTAAAAATTAACGATGGTGAAGGATACACAGGG
GATATTGTTTTTGCTAATGGAAACAGTACTTTGTACCAAAATGTTACGATAGAGCAAGGAAGGATTGTTCTTCGTGAAAAGGCAAAATTATCAGTGAATT
CTCTAAGTCAGACAGGTGGGAGTCTGTATATGGAAGCTGGGAGTACATTGGATTTTGTAACTCCACAACCACCACAACAGCCTCCTGCCGCTAATCAGTT
GATCACGCTTTCCAATCTGCATTTGTCTCTTTCTTCTTTGTTAGCAAACAATGCAGTTACGAATCCTCCTACCAATCCTCCAGCGCAAGATTCTCATCCT
GCAATCATTGGTAGCACAACTGCTGGTTCTGTTACAATTAGTGGGCCTATCTTTTTTGAGGATTTGGATGATACAGCTTATGATAGGTATGATTGGCTAG
GTTCTAATCAAAAAATCGATGTCCTGAAATTACAGTTAGGGACTCAGCCCTCAGCTAATGCCCCATCAGATTTGACTCTAGGGAATGAGATGCCTAAGTA
TGGCTATCAAGGAAGCTGGAAGCTTGCGTGGGATCCTAATACAGCAAATAATGGTCCTTATACTCTGAAAGCTACATGGACTAAAACTGGGTATAATCCT
GGGCCTGAGCGAGTAGCTTCTTTGGTTCCAAATAGTTTATGGGGATCCATTTTAGATATACGATCTGCGCATTCAGCAATTCAAGCAAGTGTGGATGGGC
GCTCTTATTGTCGAGGATTATGGGTTTCTGGAGTTTCGAATTTCTTCTATCATGACCGCGATGCTTTAGGTCAGGGATATCGGTATATTAGTGGGGGTTA
TTCCTTAGGAGCAAACTCCTACTTTGGATCATCGATGTTTGGTCTAGCATTTACCGAAGTATTTGGTAGATCTAAAGATTATGTAGTGTGTCGTTCCAAT
CATCATGCTTGCATAGGATCCGTTTATCTATCTACCAAACAAGCTTTATGTGGATCCTATTTGTTCGGAGATGCGTTTATCCGTGCTAGCTACGGGTTTG
GGAACCAGCATATGAAAACCTCATACACATTTGCAGAGGAGAGCGATGTTCGTTGGGATAATAACTGTCTGGTTGGAGAGATTGGAGTGGGATTACCGAT
TGTGATTACTCCATCTAAGCTCTATTTGAATGAGTTGCGTCCTTTCGTGCAAGCTGAGTTTTCTTATGCCGATCATGAATCTTTTACAGAGGAAGGCGAT
CAAGCTCGGGCATTCAGGAGTGGACATCTCATGAATCTATCAGTTCCTGTTGGAGTAAAATTTGATCGATGTTCTAGTACACACCCTAATAAATATAGCT
TTATGGGGGCTTATATCTGTGATGCTTATCGCACCATCTCTGGGACTCAGACAACACTCCTATCCCATCAAGAGACATGGACAACAGATGCCTTTCATTT
GGCAAGACATGGAGTCATAGTTAGAGGGTCTATGTATGCTTCTCTAACAAGCAATATAGAAGTATATGGCCATGGAAGATATGAGTATCGAGATACTTCT
CGAGGTTATGGTTTGAGTGCAGGAAGTAAAGTCCGGTTCTAA
SEQ ID 95:
MPFSLRSTSFCFLACLCSYSYGFASSPQVLTPNVTTPFKGDDVYLNGDCAFVNVYAGAENGSIISANGDWLTITGQNHTLSFTDSQGPVLQNYAFISAGE
TLTLKDFSSLMFSKNVSCGEKGMISGKTVSISGAGEVIFWDNSVGYSPLSIVPASTPTPPAPAPAPAASSSLSPTVSDARKGSIFSVETSLEISGVKKGV
MFDNNAGNFGTVFRGNSNNNAGSGGSGSATTPSFTVKNCKGKVSFTDNVASCGGGVVYKGTVLFKDNEGGIFFRGNTAYDDLGILAATSRDQNTETGGGG
GVICSPDDSVKFEGNKGSIVFDYNFAKGRGGSILTKEFSLVADDSVVFSNNTAEKGGGAIYAPTIDISTNGGSILFERNRAAEGGAICVSEASSGSTGNL
TLSASDGDIVFSGNMTSDRPGERSAARILSDGTTVSLNASGLSKLIFYDPVVQNNSAAGASTPSPSSSSMPGAVTINQSGNGSVIFTAESLTPSEKLQVL
NSTSNFPGALTVSGGELVVTEGATLTTGTITATSGRVTLGSGASLSAVAGAANNNYTCTVSKLGIDLESFLTPNYKTAILGADGTVTVNSGSTLDLVMES
EAEVYDNPLFVGSLTIPFVTLSSSSASNGVTKNSVTINDADAAHYGYQGSWSADWTKPPLAPDAKGMVPPNTNNTLYLTWRPASNYGEYRLDPQRKGELV
PNSLWVAGSALRTFTNGLKEHYVSRDVGFVASLHALGDYILNYTQDDRDGFLARYGGFQATAASHYENGSIFGVAFGQLYGQTKSRMYYSKDAGNMTMLS
CFGRSYVDIKGTETVMYWETAYGYSVHRMHTQYFNDKTQKFDHSKCHWHNNNYYAFVGAEHNFLEYCIPTRQFARDYELTGFMRFEMAGGWSSSTRETGS
LTRYFARGSGHNMSLPIGIVAHAVSHVRRSPPSKLTLNMGYRPDIWRVTPHCNMEIIANGVKTPIQGSPLARHAFFLEVHDTLYIHHFGRAYMNYSLDAR
RRQTAHFVSMGLNRIF
SEQ ID 96:
ATGCCTTTTTCTTTGAGATCTACATCATTTTGTTTTTTAGCTTGTTTGTGTTCCTATTCGTATGGATTCGCGAGCTCTCCTCAAGTGTTAACACCTAATG
TAACCACTCCTTTTAAGGGGGACGATGTTTACTTGAATGGAGACTGCGCTTTTGTCAATGTCTATGCAGGGGCAGAGAACGGCTCAATTATCTCAGCTAA
TGGCGACAATTTAACGATTACCGGACAAAACCATACATTATCATTTACAGATTCTCAAGGGCCAGTTCTTCAAAATTATGCCTTCATTTCAGCAGGAGAG
ACACTTACTCTGAAAGATTTTTCGAGTTTGATGTTCTCGAAAAATGTTTCTTGCGGAGAAAAGGGAATGATCTCAGGGAAAACCGTGAGTATTTCCGGAG
CAGGCGAAGTGATTTTTTGGGATAACTCTGTGGGGTATTCTCCTTTGTCTATTGTGCCAGCATCGACTCCAACTCCTCCAGCACCAGCACCAGCTCCTGC
TGCTTCAAGCTCTTTATCTCCAACAGTTAGTGATGCTCGGAAAGGGTCTATTTTTTCTGTAGAGACTAGTTTGGAGATCTCAGGCGTCAAAAAAGGGGTC
ATGTTCGATAATAATGCCGGGAATTTTGGAACAGTTTTTCGAGGTAATAGTAATAATAATGCTGGTAGTGGGGGTAGTGGGTCTGCTACAACACCAAGTT
TTACAGTTAAAAACTGTAAAGGGAAAGTTTCTTTCACAGATAACGTAGCCTCCTGTGGAGGCGGAGTAGTCTACAAAGGAACTGTGCTTTTCAAAGACAA
TGAAGGAGGCATATTCTTCCGAGGGAACACAGCATACGATGATTTAGGGATTCTTGCTGCTACTAGTCGGGATCAGAATACGGAGACAGGAGGCGGTGGA
GGAGTTATTTGCTCTCCAGATGATTCTGTAAAGTTTGAAGGCAATAAAGGTTCTATTGTTTTTGATTACAACTTTGCAAAAGGCAGAGGCGGAAGCATCC
TAACGAAAGAATTCTCTCTTGTAGCAGATGATTCGGTTGTCTTTAGTAACAATACAGCAGAAAAAGGCGGTGGAGCTATTTATGCTCCTACTATCGATAT
AAGCACGAATGGAGGATCGATTCTATTTGAAAGAAACCGAGCTGCAGAAGGAGGCGCCATCTGCGTGAGTGAAGCAAGCTCTGGTTCAACTGGAAATCTT
ACTTTAAGCGCTTCTGATGGGGATATTGTTTTTTCTGGGAATATGACGAGTGATCGTCCTGGAGAGCGCAGCGCAGCAAGAATCTTAAGTGATGGAACGA
CTGTTTCTTTAAATGCTTCCGGACTATCGAAGCTGATCTTTTATGATCCTGTAGTACAAAATAATTCAGCAGCGGGTGCATCGACACCATCACCATCTTC
TTCTTCTATGCCTGGTGCTGTCACGATTAATCAGTCCGGTAATGGATCTGTGATTTTTACCGCCGAGTCATTGACTCCTTCAGAAAAACTTCAAGTTCTT
AACTCTACTTCTAACTTCCCAGGAGCTCTGACTGTGTCAGGAGGGGAGTTGGTTGTGACGGAAGGAGCTACCTTAACTACTGGGACCATTACAGCCACCT
CTGGACGAGTGACTTTAGGATCCGGAGCTTCGTTGTCTGCCGTTGCAGGTGCTGCAAATAATAATTATACTTGTACAGTATCTAAGTTGGGGATTGATTT
AGAATCCTTTTTAACTCCTAACTATAAGACGGCCATACTGGGTGCGGATGGAACAGTTACTGTTAACAGCGGCTCTACTTTAGACCTAGTGATGGAGAGT
GAGGCAGAGGTATATGATAATCCGCTTTTTGTGGGATCGCTGACAATTCCTTTTGTTACTCTATCTTCTAGTAGTGCTAGTAACGGAGTTACAAAAAATT
CTGTCACTATTAATGATGCAGACGCTGCGCACTATGGGTATCAAGGCTCTTGGTCTGCAGATTGGACGAAACCGCCTCTGGCTCCTGATGCTAAGGGGAT
GGTACCTCCTAATACCAATAACACTCTGTATCTGACATGGAGACCTGCTTCGAATTACGGTGAATATCGACTGGATCCTCAGAGAAAGGGAGAACTAGTA
CCCAACTCTCTTTGGGTAGCGGGATCTGCATTAAGAACCTTTACTAATGGTTTGAAAGAACACTATGTTTCTAGAGATGTTGGATTTGTAGCATCTCTGC
ATGCTCTCGGGGATTATATTTTGAATTATACGCAAGATGATCGGGATGGCTTTTTAGCTAGATATGGGGGATTCCAGGCGACCGCAGCCTCCCATTATGA
AAATGGGTCAATATTTGGAGTGGCTTTTGGACAACTCTATGGTCAGACAAAGAGCAGAATGTATTACTCTAAAGATGCTGGGAACATGACGATGTTGTCC
TGTTTCGGAAGAAGTTACGTAGATATTAAAGGAACAGAAACTGTTATGTATTGGGAGACGGCTTATGGCTATTCTGTGCACAGAATGCATACGCAGTATT
TTAATGACAAAACGCAGAAGTTCGATCATTCGAAATGTCATTGGCACAACAATAACTATTATGCGTTTGTGGGTGCCGAGCATAATTTCTTAGAGTACTG
CATTCCTACTCGTCAGTTCGCTAGAGATTATGAGCTTACAGGGTTTATGCGTTTTGAAATGGCCGGAGGATGGTCCAGTTCTACACGAGAAACTGGCTCC
CTAACTAGATATTTCGCTCGCGGGTCAGGGCATAATATGTCGCTTCCAATAGGAATTGTAGCTCATGCAGTTTCTCATGTGCGAAGATCTCCTCCTTCTA
AACTGACACTAAATATGGGATATAGACCAGACATTTGGCGTGTCACTCCACATTGCAATATGGAAATTATTGCTAACGGAGTGAAGACACCTATACAAGG
ATCTCCGCTGGCACGGCATGCCTTCTTCTTAGAAGTGCATGATACTTTGTATATTCATCATTTTGGAAGAGCCTATATGAACTATTCGCTGGATGCTCGT
CGTCGACAAACGGCACATTTTGTATCCATGGGCTTGAATAGAATCTTTTAA
SEQ ID 97:
MKKAFFFFLIGNSLSGLAREVPSRIFLMPNSVPDPTKESLSNKISLTGDTHNLTNCYLDNLRYILAILQKTPNEGAAVTLTDYLSFFDTQKEGIYFAKNL
TPESGGAIGYASPNSPTVEIRDTIGPVIFENNTCCRLFTWRNPYAADKIREGGAIHAQNLYINHNHDVVGFMKNFSYVQGGAISTANTFVVSENQSCFLF
MDNICIQTNTAGKGGAIYAGTSNSFESNNCDLFFINNACCAGGAIFSPICSLTGNRGNIVFYNNRCFKNVETASSEASDGGAIKVTTRLDVTGNRGRIFF
SDNITKNYGGAIYAPVVTLVDNGPTYFINNIANNKGGAIYIDGTSNSKISADRHAIIFNENIVTNVTNANGTSTSANPPRRNAITVASSSGEILLGAGSS
QNLIFYDPIEVSNAGVSVSFNKEADQTGSVVFSGATVNSADFHQRNLQTKTPAPLTLSNGFLCIEDHAQLTVNRFTQTGGVVSLGNGAVLSCYKNGTGDS
ASNASITLKHIGLNLSSILKSGAEIPLLWVEPTNNSNNYTADTAATFSLSDVKLSLIDDYGNSPYESTDLTHALSSQPMLSISEASDNQLQSENIDFSGL
NVPHYGWQGLWTWGWAKTQDPEPASSATITDPQKANRFHRTLLLTWLPAGYVPSPKHRSPLIANTLWGNMLLATESLKNSAELTPSGHPFWGITGGGLGM
MVYQDPRENHPGFHMRSSGYSAGMIAGQTHTFSLKFSQTYTKLNERYAKNNVSSKNYSCQGEMLFSLQEGFLLTKLVGLYSYGDHNCHHFYTQGENLTSQ
GTFRSQTMGGAVFFDLPMKPFGSTHILTAPFLGALGIYSSLSHFTEVGAYPRSFSTKTPLINVLVPIGVKGSFMNATHRPQAWTVELAYQPVLYRQEPGI
AAQLLASKGIWFGSGSPSSRHAMSYKISQQTQPLSWLTLHFQYHGFYSSSTFCNYLNGEIALRF
SEQ ID 98:
ATGAAAAAAGCGTTTTTCTTTTTCCTTATCGGAAACTCCCTATCAGGACTAGCTAGAGAGGTTCCTTCTAGAATCTTTCTTATGCCCAACTCAGTTCCAG
ATCCTACGAAAGAGTCGCTATCAAATAAAATTAGTTTGACAGGAGACACTCACAATCTCACTAACTGCTATCTCGATAACCTACGCTACATACTGGCTAT
TCTACAAAAAACTCCCAATGAAGGAGCTGCTGTCACAATAACAGATTACCTAAGCTTTTTTGATACACAAAAAGAAGGTATTTATTTTGCAAAAAATCTC
ACCCCTGAAAGTGGTGGTGCGATTGGTTATGCGAGTCCCAATTCTCCTACCGTGGAGATTCGTGATACAATAGGTCCTGTAATCTTTGAAAATAATACTT
GTTGCAGACTATTTACATGGAGAAATCCTTATGCTGCTGATAAAATAAGAGAAGGCGGAGCCATTCATGCTCAAAATCTTTACATAAATCATAATCATGA
TGTGGTCGGATTTATGAAGAACTTTTCTTATGTCCAAGGAGGAGCCATTAGTACCGCTAATACCTTTGTTGTGAGCGAGAATCAGTCTTGTTTTCTCTTT
ATGGACAACATCTGTATTCAAACTAATACAGCAGGAAAAGGTGGCGCTATCTATGCTGGAACGAGCAATTCTTTTGAGAGTAATAACTGCGATCTCTTCT
TCATCAATAACGCCTGTTGTGCAGGAGGAGCGATCTTCTCCCCTATCTGTTCTCTAACAGGAAATCGTGGTAACATCGTTTTCTATAACAATCGCTGCTT
TAAAAATGTAGAAACAGCTTCTTCAGAAGCTTCTGATGGAGGAGCAATTAAAGTAACTACTCGCCTAGATGTTACAGGCAATCGTGGTAGGATCTTTTTT
AGTGACAATATCACAAAAAATTATGGCGGAGCTATTTACGCTCCTGTAGTTACCCTAGTGGATAATGGCCCTACCTACTTTATAAACAATATCGCCAATA
ATAAGGGGGGCGCTATCTATATAGACGGAACCAGTAACTCCAAAATTTCTGCCGACCGCCATGCTATTATTTTTAATGAAAATATTGTGACTAATGTAAC
TAATGCAAATGGTACCAGTACGTCAGCTAATCCTCCTAGAAGAAATGCAATAACAGTAGCAAGCTCCTCTGGTGAAATTCTATTAGGAGCAGGGAGTAGC
CAAAATTTAATTTTTTATGATCCTATTGAAGTTAGCAATGCAGGGGTCTCTGTGTCCTTCAATAAGGAAGCTGATCAAACAGGCTCTGTAGTATTTTCAG
GAGCTACTGTTAATTCTGCAGATTTTCATCAACGCAATTTACAAACAAAAACACCTGCACCCCTTACTCTCAGTAATGGTTTTCTATGTATCGAAGATCA
TGCTCAGCTTACAGTGAATCGATTCACACAAACTGGGGGTGTTGTTTCTCTTGGGAATGGAGCAGTTCTGAGTTGCTATAAAAATGGTACAGGAGATTCT
GCTAGCAATGCCTCTATAACACTGAAGCATATTGGATTGAATCTTTCTTCCATTCTGAAAAGTGGTGCTGAGATTCCTTTATTGTGGGTAGAGCCTACAA
ATAACAGCAATAACTATACAGCAGATACTGCAGCTACCTTTTCATTAAGTGATGTAAAACTCTCACTCATTGATGACTACGGGAACTCTCCTTATGAATC
CACAGATCTGACCCATGCTCTGTCATCACAGCCTATGCTATCTATTTCTGAAGCTAGCGATAACCAGCTACAATCAGAAAATATAGATTTTTCGGGACTA
AATGTCCCTCATTATGGATGGCAAGGACTTTGGACTTGGGGCTGGGCAAAAACTCAAGATCCAGAACCAGCATCTTCAGCAACAATCACTGATCCACAAA
AAGCCAATAGATTTCATAGAACCTTACTACTAACATGGCTTCCTGCCGGGTATGTTCCTAGCCCAAAACACAGAAGTCCCCTCATAGCTAACACCTTATG
GGGGAATATGCTGCTTGCAACAGAAAGCTTAAAAAATAGTGCAGAGCTGACACCTAGTGGTCATCCTTTCTGGGGAATTACAGGAGGAGGACTAGGCATG
ATGGTTTACCAAGATCCTCGAGAAAATCATCCTGGATTCCATATGCGCTCTTCCGGATACTCTGCGGGGATGATAGCAGGGCAGACACACACCTTCTCAT
TGAAATTCAGTCAGACCTACACCAAACTCAATGAGCGTTACGCAAAAAACAACGTATCTTCTAAAAATTACTCATGCCAAGGAGAAATGCTCTTCTCATT
GCAAGAAGGTTTCTTGCTGACTAAATTAGTTGGGCTTTACAGCTATGGAGACCATAACTGTCACCATTTCTATACTCAAGGAGAAAATCTAACATCTCAA
GGGACGTTCCGCAGTCAAACGATGGGAGGTGCTGTCTTTTTTGATCTCCCTATGAAACCCTTTGGATCAACGCATATACTGACAGCTCCCTTTTTAGGTG
CTCTTGGTATTTATTCTAGCCTGTCTCACTTTACTGAGGTGGGAGCCTATCCGCGAAGCTTTTCTACAAAGACTCCTTTGATCAATGTCCTAGTCCCTAT
TGGAGTTAAAGGTAGCTTTATGAATGCTACCCACAGACCTCAAGCCTGGACTGTAGAATTGGCATACCAACCCGTTCTGTATAGACAAGAACCAGGGATC
GCAGCCCAGCTCCTAGCCAGTAAGGGTATTTGGTTCGGTAGTGGAAGCCCCTCATCGCGTCATGCCATGTCCTATAAAATCTCACAGCAAACACAACCTT
TGAGTTGGTTAACTCTCCATTTCCAGTATCATGGATTCTACTCCTCTTCAACCTTCTGTAATTATCTCAATGGGGAAATTGCTCTGCGATTCTAG
SEQ ID 99:
MKKAFFFFLIGNSLSGLAREVPSRIFLMPNSVPDPTKESLSNKISLTGDTHNLTNCYLDNLRYILAILQKTPNEGAAVTITDYLSFFDTQKEGIYFAKNL
TPESGGAIGYASPNSPTVEIRDTIGPVIFENNTCCRLFTWRNPYAADKIREGGAIHAQNLYINHNHDVVGFMKNFSYVQGGAISTANTFVVSENQSCFLF
MDNICIQTNTAGKGGAIYAGTSNSFESNNCDLFFINNACCAGGAIFSPICSLTGNRGNIVFYNNRCFKNVETASSEASDGGAIKVTTRLDVTGNRGRIFF
SDNITKNYGGAIYAPVVTLVDNGPTYFINNIANNKGGAIYIDGTSNSKISADRHAIIFNENIVTNVTNANGTSTSANPPRRNAITVASSSGEILLGAGSS
QNLIFYDPIEVSNAGVSVSFNKEADQTGSVVFSGATVNSADFHQRNLQTKTPAPLTLSNGFLCIEDHAQLTVNRFTQTGGVVSLGNGAVLSCYKNGTGDS
ASNASITLKHIGLNLSSILKSGAEIPLLWVEPTNNSNNYTADTAATFSLSDVKLSLIDDYGNSPYESTDLTHALSSQPMLSISEASDNQLQSENIDFSGL
NVPHYGWQGLWTWGWAKTQDPEPASSATITDPQKANRFHRTLLLTWLPAGYVPSPKHRSPLIANTLWGNMLLATESLKNSAELTPSGHPFWGITGGGLGM
MVYQDPRENHPGFHMRSSGYSAGMIAGQTHTFSLKFSQTYTKLNERYAKNNVSSKNYSCQGEMLFSLQEGFLLTKLVGLYSYGDHNCHHFYTQGENLTSQ
GTFRSQTMGGAVFFDLPMKPFGSTHILTAPFLGALGIYSSLSHFTEVGAYPRSFSTKTPLINVLVPIGVKGSFMNATHRPQAWTVELAYQPVLYRQEPGI
AAQLLASKGIWFGSGSPSSRHAMSYKISQQTQPLSWLTLHFQYHGFYSSSTFCNYLNGEIALRF
SEQ ID 100:
ATGAAAAAAGCGTTTTTCTTTTTCCTTATCGGAAACTCCCTATCAGGACTAGCTAGAGAGGTTCCTTCTAGAATCTTTCTTATGCCCAACTCAGTTCCAG
ATCCTACGAAAGAGTCGCTATCAAATAAAATTAGTTTGACAGGAGACACTCACAATCTCACTAACTGCTATCTCGATAACCTACGCTACATACTGGCTAT
TCTACAAAAAACTCCCAATGAAGGAGCTGCTGTCACAATAACAGATTACCTAAGCTTTTTTGATACACAAAAAGAAGGTATTTATTTTGCAAAAAATCTC
ACCCCTGAAAGTGGTGGTGCGATTGGTTATGCGAGTCCCAATTCTCCTACCGTGGAGATTCGTGATACAATAGGTCCTGTAATCTTTGAAAATAATACTT
GTTGCAGACTATTTACATGGAGAAATCCTTATGCTGCTGATAAAATAAGAGAAGGCGGAGCCATTCATGCTCAAAATCTTTACATAAATCATAATCATGA
TGTGGTCGGATTTATGAAGAACTTTTCTTATGTCCAAGGAGGAGCCATTAGTACCGCTAATACCTTTGTTGTGAGCGAGAATCAGTCTTGTTTTCTCTTT
ATGGACAACATCTGTATTCAAACTAATACAGCAGGAAAAGGTGGCGCTATCTATGCTGGAACGAGCAATTCTTTTGAGAGTAATAACTGCGATCTCTTCT
TCATCAATAACGCCTGTTGTGCAGGAGGAGCGATCTTCTCCCCTATCTGTTCTCTAACAGGAAATCGTGGTAACATCGTTTTCTATAACAATCGCTGCTT
TAAAAATGTAGAAACAGCTTCTTCAGAAGCTTCTGATGGAGGAGCAATTAAAGTAACTACTCGCCTAGATGTTACAGGCAATCGTGGTAGGATCTTTTTT
AGTGACAATATCACAAAAAATTATGGCGGAGCTATTTACGCTCCTGTAGTTACCCTAGTGGATAATGGCCCTACCTACTTTATAAACAATATCGCCAATA
ATAAGGGGGGCGCTATCTATATAGACGGAACCAGTAACTCCAAAATTTCTGCCGACCGCCATGCTATTATTTTTAATGAAAATATTGTGACTAATGTAAC
TAATGCAAATGGTACCAGTACGTCAGCTAATCCTCCTAGAAGAAATGCAATAACAGTAGCAAGCTCCTCTGGTGAAATTCTATTAGGAGCAGGGAGTAGC
CAAAATTTAATTTTTTATGATCCTATTGAAGTTAGCAATGCAGGGGTCTCTGTGTCCTTCAATAAGGAAGCTGATCAAACAGGCTCTGTAGTATTTTCAG
GAGCTACTGTTAATTCTGCAGATTTTCATCAACGCAATTTACAAACAAAAACACCTGCACCCCTTACTCTCAGTAATGGTTTTCTATGTATCGAAGATCA
TGCTCAGCTTACAGTGAATCGATTCACACAAACTGGGGGTGTTGTTTCTCTTGGGAATGGAGCAGTTCTGAGTTGCTATAAAAATGGTACAGGAGATTCT
GCTAGCAATGCCTCTATAACACTGAAGCATATTGGATTGAATCTTTCTTCCATTCTGAAAAGTGGTGCTGAGATTCCTTTATTGTGGGTAGAGCCTACAA
ATAACAGCAATAACTATACAGCAGATACTGCAGCTACCTTTTCATTAAGTGATGTAAAACTCTCACTCATTGATGACTACGGGAACTCTCCTTATGAATC
CACAGATCTGACCCATGCTCTGTCATCACAGCCTATGCTATCTATTTCTGAAGCTAGCGATAACCAGCTACAATCAGAAAATATAGATTTTTCGGGACTA
AATGTCCCTCATTATGGATGGCAAGGACTTTGGACTTGGGGCTGGGCAAAAACTCAAGATCCAGAACCAGCATCTTCAGCAACAATCACTGATCCACAAA
AAGCCAATAGATTTCATAGAACCTTACTACTAACATGGCTTCCTGCCGGGTATGTTCCTAGCCCAAAACACAGAAGTCCCCTCATAGCTAACACCTTATG
GGGGAATATGCTGCTTGCAACAGAAAGCTTAAAAAATAGTGCAGAGCTGACACCTAGTGGTCATCCTTTCTGGGGAATTACAGGAGGAGGACTAGGCATG
ATGGTTTACCAAGATCCTCGAGAAAATCATCCTGGATTCCATATGCGCTCTTCCGGATACTCTGCGGGGATGATAGCAGGGCAGACACACACCTTCTCAT
TGAAATTCAGTCAGACCTACACCAAACTCAATGAGCGTTACGCAAAAAACAACGTATCTTCTAAAAATTACTCATGCCAAGGAGAAATGCTCTTCTCATT
GCAAGAAGGTTTCTTGCTGACTAAATTAGTTGGGCTTTACAGCTATGGAGACCATAACTGTCACCATTTCTATACTCAAGGAGAAAATCTAACATCTCAA
GGGACGTTCCGCAGTCAAACGATGGGAGGTGCTGTCTTTTTTGATCTCCCTATGAAACCCTTTGGATCAACGCATATACTGACAGCTCCCTTTTTAGGTG
CTCTTGGTATTTATTCTAGCCTGTCTCACTTTACTGAGGTGGGAGCCTATCCGCGAAGCTTTTCTACAAAGACTCCTTTGATCAATGTCCTAGTCCCTAT
TGGAGTTAAAGGTAGCTTTATGAATGCTACCCACAGACCTCAAGCCTGGACTGTAGAATTGGCATACCAACCCGTTCTGTATAGACAAGAACCAGGGATC
GCAGCCCAGCTCCTAGCCAGTAAGGGTATTTGGTTCGGTAGTGGAAGCCCCTCATCGCGTCATGCCATGTCCTATAAAATCTCACAGCAAACACAACCTT
TGAGTTGGTTAACTCTCCATTTCCAGTATCATGGATTCTACTCCTCTTCAACCTTCTGTAATTATCTCAATGGGGAAATTGCTCTGCGATTCTAG
SEQ ID 101:
MKKAFFFFLIGNSLSGLAREVPSRIFLMPNSVPDPTKESLSNKISLTGDTHNLTNCYLDNLRYILAILQKTPNEGAAVTITDYLSFFDTQKEGIYFAKNL
TPESGGAIGYASPNSPTVEIRDTIGPVIFENNTCCRLFTWRNPYAADKIREGGAIHAQNLYINHNHDVVGFMKNFSYVQGGAISTANTFVVSENQSCFLF
MDNICIQTNTAGKGGAIYAGTSNSFESNNCDLFFINNACCAGGAIFSPICSLTGNRGNIVFYNNRCFKNVETASSEASDGGAIKVTTRLDVTGNRGRIFF
SDNITKNYGGAIYAPVVTLVDNGPTYFINNIANNKGGAIYIDGTSNSKISADRHAIIFNENIVTNVTNANGTSTSANPPRRNAITVASSSGEILLGAGSS
QNLIFYDPIEVSNAGVSVSFNKEADQTGSVVFSGATVNSADFHQRNLQTKTPAPLTLSNGFLCIEDHAQLTVNRFTQTGGVVSLGNGAVLSCYKNGTGDS
ASNASITLKHIGLNLSSILKSGAEIPLLWVEPTNNSNNYTADTAATFSLSDVKLSLIDDYGNSPYESTDLTHALSSQPMLSISEASDNQLQSENIDFSGL
NVPHYGWQGLWTWGWAKTQDPEPASSATITDPQKANRFHRTLLLTWLPAGYVPSPKHRSPLIANTLWGNMLLATESLKNSAELTPSGHPFWGITGGGLGM
MVYQDPRENHPGFHMRSSGYSAGMIAGQTHTFSLKFSQTYTKLNERYAKNNVSSKNYSCQGEMLFSLQEGFLLTKLVGLYSYGDHNCHHFYTQGENLTSQ
GTFRSQTMGGAVFFDLPMKPFGSTHILTAPFLGALGIYSSLSHFTEVGAYPRSFSTKTPLINVLVPIGVKGSFMNATHRPQAWTVELAYQPVLYRQEPGI
AAQLLASKGIWFGSGSPSSRHAMSYKISQQTQPLSWLTLHFQYHGFYSSSTFCNYLNGEIALRF
SEQ ID 102:
ATGAAAAAAGCGTTTTTCTTTTTCCTTATCGGAAACTCCCTATCAGGACTAGCTAGAGAGGTTCCTTCTAGAATCTTTCTTATGCCCAACTCAGTTCCAG
ATCCTACGAAAGAGTCGCTATCAAATAAAATTAGTTTGACAGGAGACACTCACAATCTCACTAACTGCTATCTCGATAACCTACGCTACATACTGGCTAT
TCTACAAAAAACTCCCAATGAAGGAGCTGCTGTCACAATAACAGATTACCTAAGCTTTTTTGATACACAAAAAGAAGGTATTTATTTTGCAAAAAATCTC
ACCCCTGAAAGTGGTGGTGCGATTGGTTATGCGAGTCCCAATTCTCCTACCGTGGAGATTCGTGATACAATAGGTCCTGTAATCTTTGAAAATAATACTT
GTTGCAGACTATTTACATGGAGAAATCCTTATGCTGCTGATAAAATAAGAGAAGGCGGAGCCATTCATGCTCAAAATCTTTACATAAATCATAATCATGA
TGTGGTCGGATTTATGAAGAACTTTTCTTATGTCCAAGGAGGAGCCATTAGTACCGCTAATACCTTTGTTGTGAGCGAGAATCAGTCTTGTTTTCTCTTT
ATGGACAACATCTGTATTCAAACTAATACAGCAGGAAAAGGTGGCGCTATCTATGCTGGAACGAGCAATTCTTTTGAGAGTAATAACTGCGATCTCTTCT
TCATCAATAACGCCTGTTGTGCAGGAGGAGCGATCTTCTCCCCTATCTGTTCTCTAACAGGAAATCGTGGTAACATCGTTTTCTATAACAATCGCTGCTT
TAAAAATGTAGAAACAGCTTCTTCAGAAGCTTCTGATGGAGGAGCAATTAAAGTAACTACTCGCCTAGATGTTACAGGCAATCGTGGTAGGATCTTTTTT
AGTGACAATATCACAAAAAATTATGGCGGAGCTATTTACGCTCCTGTAGTTACCCTAGTGGATAATGGCCCTACCTACTTTATAAACAATATCGCCAATA
ATAAGGGGGGCGCTATCTATATAGACGGAACCAGTAACTCCAAAATTTCTGCCGACCGCCATGCTATTATTTTTAATGAAAATATTGTGACTAATGTAAC
TAATGCAAATGGTACCAGTACGTCAGCTAATCCTCCTAGAAGAAATGCAATAACAGTAGCAAGCTCCTCTGGTGAAATTCTATTAGGAGCAGGGAGTAGC
CAAAATTTAATTTTTTATGATCCTATTGAAGTTAGCAATGCAGGGGTCTCTGTGTCCTTCAATAAGGAAGCTGATCAAACAGGCTCTGTAGTATTTTCAG
GAGCTACTGTTAATTCTGCAGATTTTCATCAACGCAATTTACAAACAAAAACACCTGCACCCCTTACTCTCAGTAATGGTTTTCTATGTATCGAAGATCA
TGCTCAGCTTACAGTGAATCGATTCACACAAACTGGGGGTGTTGTTTCTCTTGGGAATGGAGCAGTTCTGAGTTGCTATAAAAATGGTACAGGAGATTCT
GCTAGCAATGCCTCTATAACACTGAAGCATATTGGATTGAATCTTTCTTCCATTCTGAAAAGTGGTGCTGAGATTCCTTTATTGTGGGTAGAGCCTACAA
ATAACAGCAATAACTATACAGCAGATACTGCAGCTACCTTTTCATTAAGTGATGTAAAACTCTCACTCATTGATGACTACGGGAACTCTCCTTATGAATC
CACAGATCTGACCCATGCTCTGTCATCACAGCCTATGCTATCTATTTCTGAAGCTAGCGATAACCAGCTACAATCAGAAAATATAGATTTTTCGGGACTA
AATGTCCCTCATTATGGATGGCAAGGACTTTGGACTTGGGGCTGGGCAAAAACTCAAGATCCAGAACCAGCATCTTCAGCAACAATCACTGATCCACAAA
AAGCCAATAGATTTCATAGAACCTTACTACTAACATGGCTTCCTGCCGGGTATGTTCCTAGCCCAAAACACAGAAGTCCCCTCATAGCTAACACCTTATG
GGGGAATATGCTGCTTGCAACAGAAAGCTTAAAAAATAGTGCAGAGCTGACACCTAGTGGTCATCCTTTCTGGGGAATTACAGGAGGAGGACTAGGCATG
ATGGTTTACCAAGATCCTCGAGAAAATCATCCTGGATTCCATATGCGCTCTTCCGGATACTCTGCGGGGATGATAGCAGGGCAGACACACACCTTCTCAT
TGAAATTCAGTCAGACCTACACCAAACTCAATGAGCGTTACGCAAAAAACAACGTATCTTCTAAAAATTACTCATGCCAAGGAGAAATGCTCTTCTCATT
GCAAGAAGGTTTCTTGCTGACTAAATTAGTTGGGCTTTACAGCTATGGAGACCATAACTGTCACCATTTCTATACTCAAGGAGAAAATCTAACATCTCAA
GGGACGTTCCGCAGTCAAACGATGGGAGGTGCTGTCTTTTTTGATCTCCCTATGAAACCCTTTGGATCAACGCATATACTGACAGCTCCCTTTTTAGGTG
CTCTTGGTATTTATTCTAGCCTGTCTCACTTTACTGAGGTGGGAGCCTATCCGCGAAGCTTTTCTACAAAGACTCCTTTGATCAATGTCCTAGTCCCTAT
TGGAGTTAAAGGTAGCTTTATGAATGCTACCCACAGACCTCAAGCCTGGACTGTAGAATTGGCATACCAACCCGTTCTGTATAGACAAGAACCAGGGATC
GCAGCCCAGCTCCTAGCCAGTAAGGGTATTTGGTTCGGTAGTGGAAGCCCCTCATCGCGTCATGCCATGTCCTATAAAATCTCACAGCAAACACAACCTT
TGAGTTGGTTAACTCTCCATTTCCAGTATCATGGATTCTACTCCTCTTCAACCTTCTGTAATTATCTCAATGGGGAAATTGCTCTGCGATTCTAG
SEQ ID 103:
MRKTVIVAMSGGVDSSVVAYLLKKQGEYNVVGLFMKNWGEQDENGECTATKDFRDVERIAEQLSIPYYTVSFSKEYKERVFSRFLREYANGYTPNPDVLC
NREIKFDLLQKKVRELKGDFLATGHYCRGGADGTGLSRGIDPNKDQSYFLCGTPKDALSNVLFPLGGMYKTEVRRIAQEAGLATATKKDSTGICFIGKRP
FKSFLEQFVADSPGDIIDFDTQQVVGRHEGAHYYTIGQRRGLNIGGMEKPCYVLSKNMEKNIVYIVRGEDHPLLYRQELLAKELNWFVPLQEPMICSAKV
RYRSPDEKCSVYPLEDGTVKVIFDVPVKAVTPGQTVAFYQGDICLGGGVIEVPMIHQL
SEQ ID 104:
GTGCGTAAAACTGTCATTGTTGCTATGTCTGGAGGAGTGGATTCCTCGGTTGTTGCTTATCTCTTAAAGAAGCAAGGGGAGTATAATGTTGTTGGGCTCT
TCATGAAAAATTGGGGAGAGCAGGACGAGAATGGTGAGTGTACTGCAACCAAAGATTTTCGCGATGTAGAGCGGATCGCAGAACAATTGTCCATTCCATA
TTACACAGTTTCCTTTTCTAAGGAATATAAAGAGCGAGTGTTTTCTAGATTTCTAAGAGAATATGCGAACGGCTACACTCCCAATCCTGATGTGTTATGC
AATCGAGAAATCAAATTTGATTTATTACAGAAGAAGGTACGTGAGCTAAAAGGTGATTTTTTAGCCACGGGACATTATTGTCGAGGAGGGGCTGATGGAA
CTGGTTTGTCCAGAGGAATAGACCCCAATAAAGACCAAAGTTATTTCTTATGTGGCACTCCTAAGGATGCTTTATCCAATGTACTTTTCCCCCTGGGAGG
TATGTATAAAACGGAGGTACGTCGAATTGCTCAAGAAGCTGGTTTAGCTACCGCCACAAAAAAAGATAGCACAGGGATTTGCTTCATTGGTAAACGGCCT
TTTAAGAGTTTCCTTGAGCAGTTTGTAGCAGACTCTCCTGGAGACATTATTGATTTTGATACACAACAGGTAGTCGGCCGACATGAAGGAGCCCATTATT
ATACGATTGGACAGCGTCGAGGGTTAAACATAGGAGGAATGGAAAAGCCTTGTTATGTTCTTAGCAAGAATATGGAAAAGAATATTGTTTACATTGTAAG
GGGTGAAGATCATCCTTTACTTTATCGACAAGAGCTTTTAGCTAAGGAACTTAATTGGTTTGTTCCCTTGCAGGAGCCTATGATCTGTAGTGCTAAAGTT
CGGTACAGATCCCCTGACGAGAAATGTTCTGTATATCCTTTGGAAGATGGAACGGTAAAAGTGATTTTCGATGTCCCTGTGAAAGCTGTCACCCCTGGAC
AGACTGTAGCTTTCTACCAGGGGGACATTTGTTTAGGAGGAGGAGTGATTGAAGTGCCTATGATTCATCAGCTGTAA
SEQ ID 105:
MCIKRKKTWIAFLAVVCSFCLTGCLKEGGDSNSEKFIVGTNATYPPFEFVDKRGEVVGFDIDLAREISNKLGKTLDVREFSFDALILNLKQHRIDAVITG
MSITPSRLKEILMIPYYGEEIKHLVLVFKGENKHPLPLTQYRSVAVQTGTYQEAYLQSLSEVHIRSFDSTLEVLMEVMHGKSPVAVLEPSIAQVVLKDFP
ALSTATIDLPEDQWVLGYGIGVASDRPALATKIEAAVQEIRKEGVLAELEQKWGLNN
SEQ ID 106:
ATGTGCATAAAAAGAAAAAAAACATGGATAGCTTTTTTAGCAGTTGTCTGTAGTTTTTGTTTGACGGGTTGTTTAAAAGAAGGGGGAGACTCCAATAGTG
AAAAATTTATTGTAGGGACTAATGCAACCTACCCTCCTTTTGAGTTTGTTGATAAGCGAGGAGAGGTTGTAGGCTTCGATATAGACTTGGCTAGAGAGAT
TAGTAACAAGCTGGGGAAAACGCTGGACGTTCGGGAGTTTTCCTTTGATGCACTCATTCTAAACCTAAAACAGCATCGGATTGATGCGGTTATAACAGGG
ATGTCCATTACTCCTTCTAGATTGAAGGAAATTCTTATGATTCCCTATTATGGGGAGGAAATAAAACACTTGGTTTTAGTGTTTAAAGGAGAGAATAAGC
ATCCATTGCCACTCACTCAATATCGTTCTGTAGCTGTTCAAACAGGAACCTATCAAGAGGCCTATTTACAGTCTCTTTCTGAAGTTCATATTCGCTCTTT
TGATAGCACTCTAGAAGTACTCATGGAAGTCATGCATGGTAAATCTCCCGTCGCTGTTTTAGAGCCATCTATCGCTCAAGTTGTCTTGAAAGATTTCCCG
GCTCTTTCTACAGCAACCATAGATCTCCCTGAAGATCAGTGGGTTTTAGGATACGGGATTGGCGTTGCTTCAGATCGCCCAGCTTTAGCCTTGAAAATCG
AGGCAGCTGTGCAAGAGATCCGAAAAGAAGGAGTGCTAGCAGAGTTGGAACAGAAGTGGGGTTTGAACAACTAA
SEQ ID 107:
MSEKRKSNKIIGIDLGTTNSCVSVMEGGQPKVIASSEGTRTTPSIVAFKGGETLVGIPAKRQAVTNPEKTLASTKRFIGRKFSEVESEIKTVPYKVAPNS
KGDAVFDVEQKLYTPEEIGAQILMKMKETAEAYLGETVTEAVITVPAYFNDSQRASTKDAGRIAGLDVKRIIPEPTAAALAYGIDKEGDKKIAVFDLGGG
TFDISILEIGDGVFEVLSTNGDTHLGGDDFDGVIINWMLDEFKKQEGIDLSKDNMALQRLKDAAEKAKIELSGVSSTEINQPFITIDANGPKHLALTLTR
AQFEHLASSLIERTKQPCAQALKDAKLSASDIDDVLLVGGMSRMPAVQAVVKEIFGKEPNKGVNPDEVVAIGAAIQGGVLGGEVKDVLLLDVIPLSLGIE
TLGGVMTPLVERNTTIPTQKKQIFSTAADNQPAVTIVVLQGERPMAKDNKEIGRFDLTDIPPAPRGHPQIEVTFDIDANGILHVSAKDAASGREQKIRIE
ASSGLKEDEIQQMIRDAELHKEEDKQRKEASDVKNEADGMIFRAEKAVKDYHDKIPAELVKEIEEHIEKVRQAIKEDASTTAIKAASDELSTHMQKIGEA
MQAQSASAAASSAAKAQGGPNINSEDLKKHSFSTRPPAGGSASSTDNIEDADVEIVDKPE
SEQ ID 108:
ATGAGCGAAAAAAGAAAGTCTAACAAAATTATTGGTATCGACCTAGGGACGACCAACTCTTGCGTCTCTGTTATGGAAGGTGGCCAACCTAAAGTTATTG
CCTCTTCTGAAGGAACTCGTACTACTCCTTCTATCGTTGCTTTTAAAGGTGGCGAAACTCTTGTTGGAATTCCTGCAAAACGTCAGGCAGTAACCAATCC
TGAAAAAACATTGGCTTCTACTAAGCGATTCATCGGTAGAAAATTCTCTGAAGTCGAATCTGAAATTAAAACAGTCCCCTACAAAGTTGCTCCTAACTCG
AAAGGAGATGCGGTCTTTGATGTGGAACAAAAACTGTACACTCCAGAAGAAATCGGCGCTCAGATCCTCATGAAGATGAAGGAAACTGCTGAGGCTTATC
TCGGAGAAACAGTAACGGAAGCAGTCATTACCGTACCAGCTTACTTTAACGATTCTCAAAGAGCTTCTACAAAAGATGCTGGACGTATCGCAGGATTAGA
TGTTAAACGCATTATTCCTGAACCAACAGCGGCCGCTCTTGCTTATGGTATTGATAAGGAAGGAGATAAAAAAATCGCCGTCTTCGACTTAGGAGGAGGA
ACTTTCGATATTTCTATCTTGGAAATCGGTGACGGAGTTTTTGAAGTTCTCTCAACCAACGGGGATACTCACTTGGGAGGAGACGACTTCGATGGAGTCA
TCATCAACTGGATGCTTGATGTTTTCAAAAAACAAGAAGGCATTGATCTAAGCAAAGATAACATGGCTTTGCAAAGATTGAAAGATGCTGCTGAAAAAGC
AAAAATAGAATTGTCTGGTGTATCGTCTACTGAAATCAATCAGCCATTCATCACTATCGACGCTAATGGACCTAAACATTTGGCTTTAACTCTAACTCGC
GCTCAATTCGAACACCTAGCTTCCTCTCTCATTGAGCGAACCAAACAACCTTGTGCTCAGGCTTTAAAAGATGCTAAATTGTCCGCTTCTGACATTGATG
ATGTTCTTCTAGTTGGCGGAATGTCCAGAATGCCTGCGGTACAAGCAGTTGTAAAAGAGATCTTTGGTAAAGAGCCTAATAAAGGCGTCAATCCAGATGA
AGTTGTAGCGATTGGAGCTGCTATTCAGGGTGGTGTCCTCGGCGGAGAAGTGAAAGACGTTCTGTTGTTGGATGTGATTCCCCTCTCTTTAGGAATTGAG
ACTCTAGGTGGGGTCATGACTCCTTTGGTAGAGAGAAACACTACAATCCCTACTCAGAAGAAGCAAATCTTCTCTACAGCCGCTGACAATCAGCCAGCAG
TGACTATCGTCGTTCTTCAAGGTGAACGGCCTATGGCGAAAGACAATAAGGAAATTGGAAGATTTGATCTAACAGACATTCCTCCTGCTCCTCGCGGCCA
TCCACAAATTGAGGTAACCTTCGATATTGATGCCAACGGAATTTTACACGTTTCTGCTAAAGATGCTGCTAGTGGACGCGAACAAAAAATCCGTATTGAA
GCAAGCTCTGGATTAAAAGAAGATGAAATTCAACAAATGATCCGCGATGCAGAGCTTCATAAAGAGGAAGACAAACAACGAAAAGAAGCTTCTGATGTGA
AAAATGAAGCCGATGGAATGATCTTTAGAGCCGAAAAAGCTGTGAAAGATTACCACGACAAAATTCCTGCAGAACTTGTTAAAGAAATTGAAGAGCATAT
TGAGAAAGTACGCCAAGCAATCAAAGAAGATGCTTCCACAACAGCTATCAAAGCAGCTTCTGATGAGTTGAGTACTCATATGCAAAAAATCGGAGAAGCT
ATGCAGGCTCAATCCGCATCCGCAGCAGCATCTTCTGCAGCGAATGCTCAAGGAGGGCCAAACATTAACTCCGAAGATCTGAAAAAACATAGTTTCAGCA
CACGACCTCCAGCAGGAGGAAGCGCCTCTTCTACAGACAACATTGAAGATGCTGATGTTGAAATTGTTGATAAACCTGAGTAA
SEQ ID 109:
MLSQFQDRLNIGCVRYVNALPFSSGLSQAPGVSLLMDTPTNLVPKLLSREIDYALTSVAATFSSPLHRVSSFGIAAYKKILSVNLHATSQFFAKEAPHIA
ATKESLSSILLLRVLCENLWNIPFPSVTLLSSDSILTQAEHYDALLLIGDTALRHPIIPGFHTYDLAASWYDLTAKPFVFAGILSLSSTISFQLQQEFSS
ALNYFQNHKEDITSKAAALLKLPESLMQEYYTLCRYELSEEDFAGLEQFRDYYDRLPQQAKYPNHVRFSCAYL
SEQ ID 110:
ATGCTTAGTCAATTCCAAGACCGTTTAAACATTGGTTGTGTACGCTACGTTAACGCTTTACCTTTTTCTAGCGGCTTATCACAAGCTCCAGGCGTCTCCT
TGCTTATGGATACCCCTACCAATCTGGTGCCTAAACTCCTGTCACGAGAAATAGATTATGCGTTAACCTCTGTAGCAGCAACATTCTCTTCTCCCTTACA
CAGAGTATCTTCCTTTGGGATCGCGGCTTATAAAAAAATCCTAAGCGTAAACTTACATGCTACTTCGCAATTTTTTGCTAAGGAAGCTCCTCATATAGCG
GCTACTAAAGAGAGTCTTTCTTCTATTTTGCTGCTACGAGTTCTATGCGAAAACCTATGGAATATTCCGTTCCCTTCCGTTACCCTACTTTCCTCGGACA
GCATTCTTACACAAGCTGAACACTATGATGCTTTATTATTGATAGGAGATACGGCATTACGCCATCCTATAATCCCAGGATTCCACACTTATGACCTAGC
AGCTTCTTGGTATGACCTGACTGCAAAACCTTTTGTTTTTGCTGGGATTCTCAGCCTTTCTTCAACTATTTCATTTCAGCTTCAACAGGAGTTCTCTTCC
GCATTGAATTATTTTCAGAATCATAAAGAAGATATTACCAGCAAAGCAGCTGCATTACTAAAACTCCCAGAATCGCTTATGCAAGAATACTATACTTTAT
GTCGCTATGAGCTTTCTGAAGAGGATTTTGCAGGGTTAGAACAGTTTAGAGACTATTATGACCGACTTCCACAACAAGCCAAATATCCAAATCATGTTCG
ATTCTCTTGCGCCTACCTATGA
SEQ ID 111:
MHDALQSILAIQELDIKMIRLMRVKKEHQNELAKIQALKTDIRRKVEEKEQEMEKLKDQIKGGEKRIQEISDQINKLENQQAAVKKMDEFNALTQEMTAA
NKERRTLEHQLSDLMDKQAGSEDLLISLKESLSSTENSSSAIEEEIRENIRKINEEGRSLLSQRTQLKETTDPELFSIYERLLNNKKDRVVVPIENRVCS
GCHIALTPQHENLVRKQDHLVFCEHCSRILYWQELQSPSAEGATTKRRRRRTAV
SEQ ID 112:
ATGCATGACGCCCTCCAAAGTATTTTGGCTATCCAAGAGCTCGATATTAAAATGATCCGTTTAATGCGGGTCAAAAAAGAACATCAGAACGAGCTCGCTA
AAATTCAAGCTTTAAAAACGGATATCCGTCGCAAGGTGGAAGAAAAAGAACAAGAAATGGAGAAGCTGAAAGATCAGATCAAAGGCGGAGAAAAACGTAT
TCAAGAAATTTCTGATCAGATCAATAAATTAGAAAATCAGCAAGCTGCTGTAAAAAAAATGGATGAGTTTAATGCTCTAACCCAAGAGATGACCGCAGCT
AATAAAGAGCGTCGCACTTTGGAGCACCAACTTAGCGATCTTATGGATAAGCAAGCTGGTAGCGAAGATCTTCTTATCTCTCTGAAAGAAAGTCTCTCTT
CTACGGAAAATAGTAGCAGTGCTATCGAAGAAGAAATTCGAGAGAATATTCGAAAAATTAATGAAGAAGGTCGTTCTTTACTAAGTCAGAGAACACAGCT
GAAAGAAACGACAGATCCAGAATTATTTAGCATCTACGAGCGCTTGCTCAACAACAAGAAAGACCGAGTTGTTGTCCCTATCGAAAATCGTGTTTGCAGT
GGCTGTCATATAGCTCTTACCCCGCAACATGAGAATTTGGTACGTAAACAAGATCATCTTGTATTTTGTGAACACTGCTCAAGAATTCTTTACTGGCAAG
AGTTGCAATCTCCATCAGCAGAAGGCGCAACTACAAAACGTCGTCGTCGTCGTACTGCAGTATAA
SEQ ID 113:
MNRVIEIHAHYDQRQLSQSPNTNFLVHHPYLTLIPKFLLGALIVYAPYSFAEMELAISGHKQGKDRDTFTMISSCPEGTNYIINRKLILSDFSLLNKVSS
GGAFRNLAGKISFLGKNSSASIHFKHININGFGAGVFSESSIEFTDLRKLVAFGSESTGGIFTAKEDISFKNNHHIAFRNNITKGNGGVIQLQGDMKGSV
SFVDQRGAIIFTNNQAVTSSSMKHSGRGGAISGDFAGSRILFLNNQQITFEGNSAVHGGAIYNKNGLVEFLGNAGPLAFKENTTIANGGAIYTSNFKANQ
QTSPILFSQNHANKKGGAIYAQYVNLEQNQDTIRFEKNTAKEGGGAITSSQCSITAHNTIIFSDNAAGDLGGGAILLEGKKPSLTLIAHSGNIAFSGNTM
LHITKKASLDRHNSILIKEAPYKIQLAANKNHSIHFFDPVMALSASSSPIQINAPEYETPFFSPKGMIVFSGANLLDDAREDVANRTSIFNQPVHLYNGT
LSIENGAHLIVQSFKQTGGRISLSPGSSLALYTMNSFFHGNISSKEPLEINGLSFGVDISPSNLQAEIRAGNAPLRLSGSPSIHDPEGLFYENRDTAASP
YQMEILLTSDKIVDISKFTTDSLVTNKQSGFQGAWHFSWQPNTINNTKQKILRASWLPTGEYVLESNRVGRAVPNSLWSTFLLLQTASHNLGDHLCNNRS
LIPTSYEGVLIGGTGAEMSTHSSEEESFISRLGATGTSIIRLTPSLTLSGGGSHMFGDSFVADLPEHITSEGIVQNVGLTHVWGPLTVNSTLCAALDHNA
MVRICSKKDHTYGKWDTFGMRGTLGASYTFLEYDQTMRVFSFANIEATNILQRAFTETGYNPRSFSKTKLLNIAIPIGIGYEFCLGNSSFALLGKGSIGY
SRDIKRENPSTLAHLAMNDFAWTTNGCSVPTSAHTLANQLILRYKACSLYITAYTINREGKNLSNSLSCGGYVGF
SEQ ID 114:
ATGAATCGAGTTATAGAAATCCATGCTCACTACGATCAAAGACAACTTTCTCAATCTCCAAATACAAACTTCTTAGTACATCATCCTTATCTTACTCTTA
TTCCCAAGTTTCTACTAGGAGCTCTAATCGTCTATGCTCCTTATTCGTTTGCAGAAATGGAATTAGCTATTTCTGGACATAAACAAGGTAAAGATCGAGA
TACCTTTACCATGATCTCTTCCTGTCCTGAAGGCACTAATTACATCATCAATCGCAAACTCATACTCAGTGATTTCTCGTTACTAAATAAAGTTTCATCA
GGGGGAGCCTTTCGGAATCTAGCAGGGAAAATTTCCTTCTTAGGAAAAAATTCTTCTGCGTCCATTCATTTTAAACACATTAATATCAATGGTTTTGGAG
CCGGAGTCTTTTCTGAATCCTCTATTGAATTTACTGATTTACGAAAACTTGTTGCTTTTGGATCTGAAAGCACAGGAGGAATTTTTACTGCGAAAGAGGA
CATCTCTTTTAAAAACAACCACCACATTGCCTTCCGCAATAATATCACCAAAGGGAATGGTGGCGTTATCCAGCTCCAAGGAGATATGAAAGGAAGCGTA
TCCTTTGTAGATCAACGTGGAGCTATCATCTTTACCAATAACCAAGCTGTAACTTCTTCATCAATGAAACATAGTGGTCGTGGAGGAGCAATTAGCGGTG
ACTTCGCAGGATCCAGAATTCTTTTTCTTAATAACCAACAAATTACTTTCGAAGGCAATAGCGCTGTGCATGGAGGTGCTATCTACAATAAGAATGGCCT
TGTCGAGTTCTTAGGAAATGCAGGACCTCTTGCCTTTAAAGAGAACACAACAATAGCTAACGGGGGAGCTATATACACAAGTAATTTCAAAGCGAATCAA
CAAACATCCCCCATTCTATTCTCTCAAAATCATGCGAATAAGAAAGGCGGAGCGATTTACGCGCAATATGTGAACTTAGAACAGAATCAAGATACTATTC
GCTTTGAAAAAAATACCGCTAAAGAAGGCGGTGGAGCCATCACCTCTTCTCAATGCTCAATTACTGCTCATAATACCATCATTTTTTCCGATAATGCTGC
CGGAGATCTTGGAGGAGGAGCAATTCTTCTAGAAGGGAAAAAACCTTCTCTAACCTTGATTGCTCATAGTGGTAATATTGCATTTAGCGGCAATACCATG
CTTCATATCACCAAAAAAGCTTCCCTAGATCGACACAATTCTATCTTAATCAAAGAAGCTCCCTATAAAATCCAACTTGCAGCGAACAAAAACCATTCTA
TTCATTTCTTTGATCCTGTCATGGCATTGTCAGCATCATCTTCCCCTATACAAATCAATGCTCCTGAGTATGAA CTCCCTTCTTCTCACCTAAGGGTAT
GATCGTTTTCTCGGGTGCGAATCTTTTAGATGATGCTAGGGAAGATGTTGCAAATAGAACATCGATTTTTAACCAACCCGTTCATCTATATAATGGCACC
CTATCTATCGAAAATGGAGCCCATCTGATTGTCCAAAGCTTCAAACAGACCGGAGGACGTATCAGTTTATCTCCAGGATCCTCCTTGGCTCTATACACGA
TGAACTCGTTCTTCCATGGCAACATATCCAGCAAAGAACCCCTAGAAATTAATGGTTTAAGCTTTGGAGTAGATATCTCTCCTTCTAATCTTCAAGCAGA
GATCCGTGCCGGCAACGCTCCTTTACGATTATCCGGATCCCCATCTATCCATGATCCTGAAGGATTATTCTACGAAAATCGCGATACTGCAGCATCACCA
TACCAAATGGAAATCTTGCTCACCTCTGATAAAATTGTAGATATCTCCAAATTTACTACTGATTCTCTAGTTACGAACAAACAATCAGGATTCCAAGGAG
CCTGGCATTTTAGCTGGCAGCCAAATACTATAAACAATACTAAACAAAAAATATTAAGAGCTTCTTGGCTCCCAACAGGAGAATATGTCCTTGAATCCAA
TCGAGTGGGGCGTGCCGTTCCTAATTCCTTATGGAGCACATTTTTACTTTTACAGACAGCCTCTCATAACTTAGGCGATCATCTATGTAATAATCGATCT
CTTATTCCTACTTCATACTTCGGAGTTTTAATTGGAGGAACTGGAGCAGAAATGTCTACCCACTCCTCAGAAGAAGAAAGCTTTATATCTCGTTTAGGAG
CTACAGGAACCTCTATCATACGCTTAACTCCCTCCCTGACACTCTCTGGAGGAGGCTCACATATGTTCGGAGATTCGTTCGTTGCAGACTTACCAGAACA
CATCACTTCAGAAGGAATTGTTCAGAATGTCGGTTTAACCCATGTCTGGGGACCCCTTACTGTCAATTCTACATTATGTGCAGCCTTAGATCACAACGCG
ATGGTCCGCATATGCTCCAAAAAAGATCACACCTATGGGAAATGGGATACATTCGGTATGCGAGGAACATTAGGAGCCTCTTATACATTCCTAGAATATG
ATCAAACTATGCGCGTATTCTCATTCGCCAACATCGAAGCCACAAATATCTTGCAAAGAGCTTTTACTGAAACAGGCTATAACCCAAGAAGTTTTTCCAA
GACAAAACTTCTAAACATCGCCATCCCCATAGGGATTGGTTATGAATTCTGCTTAGGGAATAGCTCTTTTGCTCTACTAGGTAAGGGATCCATCGGTTAC
TCTCGAGATATTAAACGAGAAAACCCATCCACTCTTGCTCACCTGGCTATGAATGATTTTGCTTGGACTACCAATGGCTGTTCAGTTCCAACCTCTGCAC
ACACATTGGCAAATCAATTGATTCTTCGCTATAAAGCATGTTCCTTATACATCACGGCATATACTATCAACCGTGAAGGGAAGAACCTCTCCAATAGCTT
ATCCTGCGGAGGCTATGTTGGCTTCTAA
SEQ ID 115:
MKWLSATAVFAAVLPSVSGFCFPEPKELNFSRVGTSSSTTFTETVGEAGAEYIVSGNASFTKFTNIPTTDTTTPTNSNSSSSNGETASVSEDSDSTTTTP
DPKGGGAFYNAHSGVLSFMTRSGTEGSLTLSEIKITGEGGAIFSQGELLFTDLTGLTIQNNLSQLSGGAIFGESTISLSGITKATFSSNSAEVPAPVKKP
TEPKAQTASETSGSSSSSGNDSVSSPSSSRAEPAAANLQSHFICATATPAAQTDTETSTPSHKPGSGGAIYAKGDLTIADSQEVLFSINKATKDGGAIFA
EKDVSFENITSLKVQTNGAEEKGGAIYAKGDLSIQSSKQSLFNSNYSKQGGGALYVEGDINFQDLEEIRIKYNKAGTFETKKITLPKAQASAGNADAWAS
SSPQSGSGATTVSNSGDSSSGSDSDTSETVPATAKGGGLYTDKNLSITNITGIIEIANNKATDVGGGAYVKGTLTCENSHRLQFLKNSSDKQGGGIYGED
NITLSNLTGKTLFQENTAKEEGGGLFIKGTDKALTMTGLDSFCLINNTSEKHGGGAFVTKEISQTYTSDVETIPGITPVHGETVITGNKSTGGNGGGVCT
KRLALSNLQSISISGNSAAENGGGAHTCPDSFPTADTAEQPAAASAATSTPESAPVVSTALSTPSSSTVSSLTLLAASSQASPATSNKETQDPNADTDLL
IDYVVDTTISKNTAKKGGGIYAKKAKMSRIDQLNISENSATEIGGGICCKESLELDALVSLSVTENLVGKEGGGLHAKTVNISNLKSGFSFSNNKANSSS
TGVATTASAPAAAAASLQAAAAAVPSSPATPTYSGVVGGAIYGEKVTFSQCSGTCQFSGNQAIDNNPSQSSLNVQGGAIYAKTSLSIGSSDAGTSYIFSG
NSVSTGKSQTTGQIAGGAIYSPTVTLNCPATFSNNTASMATPKTSSEDGSSGNSIKDTIGGAIAGTAITLSGVSRFSGNTADLGAAIGTLANANTPSATS
GSQNSITEKITLENGSFIFERNQANKRGAIYSPSVSIKGNNITFNQNTSTHDGSAIYFTKDATIESLGSVLFTGNNVTATQASSATSGQNTNTANYGAAI
FGDPGTTQSSQTDAILTLLASSGNITFSNNSLQNNQGDTPASKFCSIAGYVKLSLQAAKGKTISFFDCVHTSTKKIGSTQNVYETLDINKEENSNPYTGT
IVFSSELHENKSYIPQNAILHNGTLVLKEKTELHVVSFEQKEGSKLIMKPGAVLSNQNIANGALVINGLTIDLSSMGTPQAGEIFSPPELRIVATTSSAS
GGSGVSSSIPTNPKRISAAAPSGSAATTPTMSENKVFLTGDLTLIDPNGNFYQNPMLGSDLDVPLIKLPTNTSDVQVYDLTLSGDLFPQKGYMGTWTLDS
NPQTGKLQARWTFDTYRRWVYIPRDNHFYANSILGSQNSMIVVKQGLINNMLNNARFDDIAYNNFWVSGVGTFLAQQGTPLSEEFSYYSRGTSVAIDAKP
RQDFILGAAFSKMVGKTKAIKKMHNYFHKGSEYSYQASVYGGKFLYFLLNKQHGWALPFLIQGVVSYGHIKHDTTTLYPSIHERNKGDWEDLGWLADLRI
SMDLKEPSKDSSKRITVYGELEYSSIRQKQFTEIDYDPRHFDDCAYRNLSLPVGCAVEGAIMNCNILMYNKLALAYMPSIYRNNPVCKYRVLSSNEAGQV
ICGVPTRTSARAEYSTQLYLGPFWTLYGNYTIDVGMYTLSQMTSCGARMIF
SEQ ID 116:
ATGAAATGGCTGTCAGCTACTGCGGTGTTTGCTGCTGTTCTCCCCTCAGTTTCAGGGTTTTGCTTCCCAGAACCTAAAGAATTAAATTTCTCTCGCGTAG
GAACTTCTTCCTCTACCACTTTTACTGAAACAGTTGGAGAAGCTGGGGCAGAATATATCGTCTCTGGTAACGCATCTTTCACAAAATTTACCAACATTCC
TACTACCGATACAACAACTCCCACGAACTCAAACTCCTCTAGCTCTAACGGAGAGACTGCTTCCGTTTCTGAGGATAGTGACTCTACAACAACGACTCCT
GATCCTAAAGGTGGCGGCGCCTTTTATAACGCGCACTCCGGAGTTTTATCCTTTATGACACGATCAGGAACAGAAGGTTCCTTAACTCTGTCTGAGATAA
AAATAACTGGTGAAGGCGGTGCTATCTTCTCTCAAGGAGAGCTGCTATTTACAGATCTGACAGGTCTAACCATCCAAAATAACTTATCCCAGCTATCCGG
AGGAGCGATTTTTGGAGAATCTACAATCTCCCTATCAGGGATTACTAAAGCGACTTTCTCCTCCAACTCTGCAGAAGTTCCTGCTCCTGTTAAGAAACCT
ACAGAACCTAAAGCTCAAACAGCAAGCGAAACGTCGGGTTCTAGTAGTTCTAGCGGAAATGATTCGGTGTCTTCCCCCAGTTCCAGTAGAGCTGAACCCG
CAGCAGCTAATCTTCAAAGTCACTTTATTTGTGCTACAGCTACTCCTGCTGCTCAAACCGATACAGAAACATCAACTCCCTCTCATAAGCCAGGATCTGG
GGGAGCTATCTATGCTAAAGGCGACCTTACTATCGCAGACTCTCAAGAGGTACTATTCTCAATAAATAAAGCTACTAAAGATGGAGGAGCGATCTTTGCT
GAGAAAGATGTTTCTTTCGAGAATATTACATCATAAAAAGTACAAACTAACGGTGCTGAAGAAAAGGGAGGAGCTATCTATGCTAAAGGTGACCTCTCAA
TTCAATCTTCTAAACAGAGTCTTTTTAATTCTAACTACAGTAAACAAGGTGGTGGGGCTCTATATGTTGAAGGAGATATAAACTTCCAAGATCTTGAAGA
AATTCGCATTAAGTACAATAAAGCTGGAACGTTCGAAACAAAAAAAATCACTTTACCAAAAGCTCAAGCATCTGCAGGAAATGCAGATGCTTGGGCCTCT
TCCTCTCCTCAATCTGGTTCTGGAGCAACTACAGTCTCCAACTCAGGAGACTCTAGCTCTGGCTCAGACTCGGATACCTCAGAAACAGTTCCAGCCACAG
CTAAAGGCGGTGGGCTTTATACTGATAAGAATCTTTCGATTACTAACATCACAGGAATTATCGAAATTGCAAATAACAAAGCGACAGATGTTGGAGGTGG
TGCTTACGTAAAAGGAACCCTTACTTGTGAAAACTCTCACCGTCTACAATTTTTGAAAAACTCTTCCGATAAACAAGGTGGAGGAATCTACGGAGAAGAC
AACATCACCCTATCTAATTTGACAGGGAAGACTCTATTCCAAGAGAATACTGCCAAAGAAGAGGGCGGTGGACTCTTCATAAAAGGTACAGATAAAGCTC
TTACAATGACAGGACTGGATAGTTTCTGTTTAATTAATAACACATCAGAAAAACATGGTGGTGGAGCCTTTGTTACCAAAGAAATCTCTCAGACTTACAC
CTCTGATGTGGAAACAATTCCAGGAATCACGCCTGTACATGGTGAAACAGTCATTACTGGCAATAAATCTACAGGAGGTAATGGTGGAGGCGTGTGTACA
AAACGTCTTGCCTTATCTAACCTTCAAAGCATTTCTATATCCGGGAATTCTGCAGCTGAAAATGGTGGTGGAGCCCACACATGCCCAGATAGCTTCCCAA
CGGCGGATACTGCAGAACAGCCCGCAGCAGCTTCTGCCGCGACGTCTACTCCCGAGTCTGCCCCAGTGGTCTCAACTGCTCTAAGCACACCTTCATCTTC
TACCGTCTCTTCATTAACCTTACTAGCAGCCTCTTCACAAGCCTCTCCTGCAACCTCTAATAAGGAAACTCAAGATCCTAATGCTGATACAGACTTATTG
ATCGATTATGTAGTTGATACGACTATCAGCAAAAACACTGCTAAGAAAGGCGGTGGAATCTATGCTAAAAAAGCCAAGATGTCCCGCATAGACCAACTGA
ATATCTCTGAGAACTCCGCTACAGAGATAGGTGGAGGTATCTGCTGTAAAGAATCTTTAGAACTAGATGCCCTAGTCTCCTTATCTGTAACAGAGAACCT
TGTTGGGAAAGAAGGTGGAGGCTTACATGCTAAAACTGTAAATATTTCTAATCTGAAATCAGGCTTCTCTTTCTCGAACAACAAAGCAAACTCCTCATCC
ACAGGAGTCGCAACAACAGCTTCAGCACCTGCTGCAGCTGCTGCTTCCCTACAAGCAGCCGCAGCAGCCGTACCATCATCTCCAGCAACACCAACTTATT
CAGGTGTAGTAGGAGGAGCTATCTATGGAGAAAAGGTTACATTCTCTCAATGTAGCGGGACTTGTCAGTTCTCTGGGAACCAAGCTATCGATAACAATCC
CTCCCAATCATCGTTGAACGTACAAGGAGGAGCCATCTATGCCAAAACCTCTTTGTCTATTGGATCTTCCGATGCTGGAACCTCCTATATTTTCTCGGGG
AACAGTGTCTCCACTGGGAAATCTCAAACAACAGGGCAAATAGCGGGAGGAGCGATCTACTCCCCTACTGTTACATTGAATTGTCCTGCGACATTCTCTA
ACAATACAGCCTCTATGGCTACACCAAAGACTTCTTCTGAAGATGGATCCTCAGGAAATTCTATTAAAGATACCATTGGAGGAGCCATTGCAGGGACAGC
CATTACCCTATCTGGAGTCTCTCGATTTTCAGGGAATACGGCTGATTTAGGAGCTGCAATAGGAACTCTAGCTAATGCAAATACACCCAGTGCAACTAGC
GGATCTCAAAATAGCATTACAGAAAAAATTACTTTAGAAAACGGTTCTTTTATTTTTGAAAGAAACCAAGCTAATAAACGTGGAGCGATTTACTCTCCTA
GCGTTTCCATTAAAGGGAATAATATTACCTTCAATCAAAATACATCCACTCATGATGGAAGTGCTATCTACTTTACAAAAGATGCTACGATTGAGTCTTT
AGGATCTGTTCTTTTTACAGGAAATAACGTTACAGCTACACAAGCTAGTTCTGCAACATCTGGACAAAATACAAATACTGCCAACTATGGGGCAGCCATC
TTTGGAGATCCAGGAACCACTCAATCGPCTCAAACAGATGCCATTTTAACCCTTCTTGCTTCTTCTGGAAACATTACTTTTAGCAACAACAGTTTACAGA
ATAACCAAGGTGATACTCCCGCTAGCAAGTTTTGTAGTATTGCAGGATACGTCAAACTCTCTCTACAAGCCGCTAAAGGGAAGACTATTAGCTTTTTCGA
TTGTGTGCACACCTCTACCAAAAAAATAGGTTCAACACAAAACGTTTATGAAACTTTAGATATTAATAAAGAAGAGAACAGTAATCCATATACAGGAACT
ATTGTGTTCTCTTCTGAATTACATGAAAACAAATCTTACATCCCACAGAATGCAATCCTTCACAACGGAACTTTAGTTCTTAAAGAGAAAACAGAACTCC
ACGTAGTCTCTTTTGAGCAGAAAGAAGGGTCTAAATTAATTATGAAACCCGGAGCTGTGTTATCTAACCAAAACATAGCTAACGGAGCTCTAGTTATCAA
TGGGTTAACGATTGATCTTTCCAGTATGGGGACTCCTCAAGCAGGGGAAATCTTCTCTCCTCCAGAATTACGTATCGTTGCCACGACCTCTAGTGCATCC
GGAGGAAGCGGGGTCAGCAGTAGTATACCAACAAATCCTAAAAGGATTTCTGCAGCAGCGCCTTCAGGTTCTGCCGCAACTACTCCAACTATGAGCGAGA
ACAAAGTTTTCCTAACAGGAGACCTTACTTTAATAGATCCTAATGGAAACTTTTACCAAAACCCTATGTTAGGAAGCGATCTAGATGTACCACTAATTAA
GCTTCCGACTAACACAAGTGACGTCCAAGTCTATGATTTAACTTTATCTGGGGATCTTTTCCCTCAGAAAGGGTACATGGGAACCTGGACATTAGATTCT
AATCCACAAACAGGGAAACTTCAAGCCAGATGGACATTCGATACCTATCGTCGCTGGGTATACATACCTAGGGATAATCATTTTTATGCGAACTCTATCT
TAGGCTCCCAAAACTCAATGATTGTTGTGAAGCAAGGGCTTATCAACAACATGTTGAATAATGCCCGCTTCGATGATATCGCTTACAATAACTTCTGGGT
TTCAGGAGTAGGAACTTTCTTAGCTCAACAAGGAACTCCTCTTTCCGAAGAATTCAGTTACTACAGCCGCGGAACTTCAGTTGCCATCGATGCCAAACCT
AGACAAGATTTTATCCTAGGAGCTGCATTTAGTAAGATGGTGGGGAAAACCAAAGCCATCAAAAAAATGCATAATTACTTCCATAAGGGCTCTGAGTACT
CTTACCAAGCTTCTGTCTATGGAGGTAAATTCCTGTATTTCTTGCTCAATAAGCAACATGGTTGGGCACTTCCTTTCCTAATACAAGGAGTCGTGTCCTA
TGGACATATTAAACATGATACAACAACACTTTACCCTTCTATCCATGAAAGAAATAAAGGAGATTGGGAAGATTTAGGATGGTTAGCGGATCTTCGTATC
TCTATGGATCTTAAAGAACCTTCTAAAGATTCTTCTAAACGGATCACTGTCTATGGGGAACTTGAGTATTCCAGCATTCGCCAGAAACAGTTCACAGAAA
TCGATTACGATCCAAGACACTTCGATGATTGTGCTTACAGAAATCTGTCGCTTCCTGTGGGATGCGCTGTCGAAGGAGCTATCATGAACTGTAATATTCT
TATGTATAATAAGCTTGCATTAGCCTACATGCCTTCTATCTACAGAAATAATCCTGTCTGTAAATATCGGGTATTGTCTTCGAATGAAGCTGGTCAAGTT
ATCTGCGGAGTGCCAACTAGAACCTCTGCTAGAGCAGAATACAGTACTCAACTATATCTTGGTCCCTTCTGGACTCTCTACGGAAACTATACTATCGATG
TAGGCATGTATACGCTATCGCAAATGACTAGCTGCGGTGCTCGCATGATCTTCTAA
SEQ ID 117:
MRLLFLLLFSLGITCSYGDEVSTRKQILVSIVPYKFLVEQIAGDTCQVFSIVMDNHDPHNYELSPKYIEKIRQVELWFKIGEGFEKTCERIISCKQVDLA
ANIDKITNGACCQRFLSFDTHTWLSPKNLKIQIQAITEALVETAPEHETLYRKNCSLLQSQLDLLDQKISSIVSSTSQRNVLVTHGAFAYFCRDYGFIQH
TIERANHSELSPKDVVRVERTIRDHNLHSVILLKHAGKRSSAALVRKFNMTPILLDPYAEDVFNNLLAIATAFANL
SEQ ID 118:
ATGCGTTTACTCTTTTTACTCCTCTTTTCTTTGGGGATCACTTGTTCCTATGGAGACGAGGTTTCTACTCGCAAGCAGATTTTGGTCAGCATTGTCCCCT
ATAAATTTCTTGTGGAACAAATCGCGGGGGATACCTGTCAGGTGTTCTCTATTGTTATGGATAACCATGACCCTCATAACTATGAGCTTTCGCCTAAATA
TATAGAAAAGATCCGCCAGGTTGAACTTTGGTTTAAAATTGGTGAGGGATTTGAAAAAACTTGTGAGAGAATTATTTCGTGCAAGCAAGTAGATCTAGCA
GCAAATATCGATAAAATTACAAATGGGGCCTGCTGCCAGCGTTTTCTTAGTTTTGATACCCACACCTGGTTAAGTCCTAAAAACCTAAAAATTCAAATCC
AGGCCATTACAGAAGCTTTAGTGGAGACCGCCCCTGAACACGAAACTCTGTACCGTAAAAACTGTTCTCTATTACAGTCTCAACTAGATCTTTTGGATCA
AAAGATTTCTTCTATTGTTTCTAGTACATCACAACGCAATGTTCTAGTTACCCACGGAGCTTTTGCTTATTTTTGTAGAGATTACGGCTTTATACAACAT
ACTATCGAGCGAGCTAACCACTCAGAGTTATCTCCTAAAGATGTTGTTCGTGTAGAGCGAACCATTCGTGATCACAACTTGCACTCTGTAATTTTGCTCA
AGCATGCGGGGAAACGTAGTAGCGCCGCCTTAGTACGGAAGTTTAATATGACGCCTATTCTATTGGATCCCTATGCTGAAGATGTCTTCAATAATTTACT
AGCTATCGCAACGGCTTTTGCAAATCTATGA
SEQ ID 119:
MPMISILCSLFPPLLFPSLLAAFGASIAAGIIGSYIVVKRIVSISGSIAHSILGGVGIALWLQYQFNLPISPLHGAIASAIFVAICIGNVHLKYHEREDS
IISMIWSIGMAIGIICISKLPSFNSELSDFLFGNILWVTPQDLYFLGILDLFIVATVSICHTRFLALCFDEKYMALNHYSIKTWYLLLLILTAITTVVLM
YVMGVILMLSMLVLPVSIACRFSYKMSHIIYIASILNIVCSFLGIMLAYLLDLPVGPVIAILMGGAYSLSLLLKRSYNASTPSPVSPESKINS
SEQ ID 120:
ATGCCCATGATCTCTATTCTCTGTTCTTTGTTCCCGCCTCTTCTATTCCCTTCGCTGCTGGCGGCTTTCGGCGCCTCCATTGCTGCAGGAATCATAGGCT
CTTATATTGTAGTGAAACGCATTGTGTCGATTAGTGGAAGCATAGCACATTCCATTCTAGGAGGAGTTGGTATCGCCCTATGGCTTCAATACCAATTTAA
TCTCCCTATATCCCCACTACACGGGGCTATTGCTAGTGCTATCTTCGTAGCGATCTGTATTGGGAATGTCCATCTTAAATACCATGAACGCGAAGACTCC
ATCATTTCTATGATCTGGTCCATTGGTATGGCTATAGGCATTATATGTATATCTAAGCTCCCTTCCTTTAACTCAGAGCTTTCTGATTTTCTTTTTGGCA
ATATCTTATGGGTCACCCCACAAGATCTTTATTTCCTTGGGATCCTAGATCTGTTTATCGTTGCTACCGTATCCATTTGTCACACACGATTCTTAGCCCT
ATGCTTCGATGAGAAATACATGGCGTTGAATCATTACTCCATAAAAACTTGGTACCTATTGCTGCTTATCTTAACAGCAATTACGACTGTTGTTCTTATG
TATGTCATGGGAGTTATTCTAATGTTGAGCATGTTAGTCCTCCCAGTATCAATAGCCTGTCGTTTCTCCTACAAAATGAGCCACATCATTTACATCGCAT
CTATCTTAAATATCGTCTGCTCATTCCTAGGAATTATGCTTGCTTATCTCCTAGACTTGCCAGTTGGGCCTGTCATAGCGATTCTCATGGGAGGAGCTTA
CTCACTGAGTTTACTCTTGAAGAGATCATACAATGCATCTACCCCTTCTCCTGTCAGCCCTGAAAGCAAAATAAATTCTTGA
SEQ ID 121:
MMRFARFCLLVLTLFPQLAFSAEPLRRQDVRKTVDKLVEHHIDTQQISPYILSRSLEDYVRSFDSHKAYLTQDEVFSHAFSEEATRPLFKQYQEDNFSSF
KELDTCIQQSISRAREWRSSWLTDSIRVIQDAMSHTIEKKPSAWASSIEEVKQRQYDLLLSYASIYLEDAAKNRYQGKEHALVKLCIRQIENHENPYIGI
NDHGYRMSPEEEANSFHVRIIKSIAHSLDAHTAYFSQEEALSMRAQLEKGMCGIGVVLKEDIDGVVVKEVLAGGPADKTGSLRVGDIIYRVNGKNIENTP
FPGVLDSLRGSPGSSVTLDIHRQNNDHVIQLRREKILLDSRRVDVSYEPYGNGIIGKITLHSFYEGENQVSSEQDLRKAIRELQEKNLLGLVLDIRENTG
GFLSQAIKVSGLFLTNGVVVVSRYADGSVKRYRTISPQKFYDGPLAVLVSKSSASAAEIVAQTLQDYGVALIVGDQQTYGKGTIQHQTITGSNSQEDFFK
VTVGRYYSPSGKSTQLEGVKSDIVIPSRYAEDKLGERFLEYALPADQYENVINDNLGDLDINIRPWFQKYYSPHLQKPELVWREMLPQLAHNSQERLEKN
KNFEIFVQHLKKTNKQDRSFGSNDLQMEESVNIVKDMILLKSIS
SEQ ID 122:
ATGATGAGATTCGCTCGCTTTTGTCTGCTAGTTTTAACCCTATTTCCACAACTTGCGTTTTCAGCAGAGCCTCTTCGACGACAAGATGTCCGCAAAACCG
TAGATAAACTAGTCGAACATCATATTGATACGCAACAGATCTCTCCTTACATTCTCTCTCGATCTTTGGAAGATTATGTTCGTTCTTTTGATTCTCACAA
AGCGTACCTTACTCAAGACGAGGTCTTCTCCCACGCTTTTTCAGAAGAAGCAACACGTCCCCTATTTAAGCAATATCAAGAAGATAACTTTTCTTCTTTC
AAGGAATTAGATACCTGTATCCAACAAAGTATTTCTCGAGCCAGAGAATGGCGCTCATCCTGGCTCACTGATTCCATAAGAGTAATTCAAGATGCCATGT
CTCATACTATTGAGAAAAAACCAAGCGCTTGGGCTTCTTCAATTGAAGAAGTAAAGCAAAGACAATACGATCTTCTTCTTTCCTACGCATCTATCTATTT
AGAAGATGCAGCAAAAAATCGTTATCAAGGGAAAGAACATGCTTTAGTTAAACTCTGTATCCGCCAGATTGAAAACCATGAAAATCCTTATATCGGCATT
AACGATCATGGATACAGAATGTCTCCAGAGGAAGAGGCCAATAGCTTCCATGTTCGTATTATCAAATCTATTGCTCACAGCCTAGATGCGCATACCGCCT
ACTTTAGTCAGGAAGAAGCTCTATCCATGAGAGCTCAGCTGGAGAAAGGCATGTGTGGCATAGGAGTCGTGCTTAAAGAAGATATTGATGGGGTTGTGGT
TAAAGAAGTCCTTGCTGGAGGCCCTGCTGATAAAACGGGTAGCCTTCGTGTAGGTGATATTATTTACCGTGTAAATGGGAAAAATATTGAAAACACCCCT
TTCCCCGGGGTTTTAGATTCTCTAAGAGGTTCTCCAGGATCCTCCGTTACTTTAGATATCCACAGACAAAATAATGACCACGTCATTCAGTTACGTCGTG
AAAAAATTCTCTTAGATAGTCGTCGTGTCGACGTGTCTTACGAGCCGTACGGTAATGGCATTATCGGTAAGATCACCTTGCACTCTTTCTATGAAGGAGA
AAACCAAGTATCGAGCGAACAAGATCTACGTAAAGCCATTCGAGAATTACAAGAAAAAAACCTGCTTGGCTTAGTTCTTGATATTCGAGAGAATACGGGA
GGATTTTTATCTCAAGCCATCAAAGTGTCTGGGTTATTTTTAACGAATGGGGTTGTGGTTGTCTCCCGCTATGCAGATGGTTCGGTAAAACGCTACCGCA
CTATTTCTCCTCAAAAATTTTATGATGGGCCGCTAGCTGTTTTGGTTTCTAAAAGTTCCGCTTCGGCAGCAGAAATTGTTGCACAAACACTCCAGGATTA
CGGAGTAGCCCTGATCGTGGGAGATCAACAAACTTATGGAAAAGGAACCATCCAACATCAGACTATCACTGGAAGCAACAGTCAAGAAGATTTCTTTAAA
GTGACAGTGGGGAGATATTACTCTCCTTCGGGAAAATCCACACAACTCGAAGGAGTGAAATCAGACATTGTTATCCCCTCACGTTATGCAGAAGATAAAC
TCGGAGAACGCTTTTTAGAGTATGCTCTACCAGCTGATCAATACGAAAATGTGATCAATGACAACCTGGGAGACCTAGATATCAACATCCGTCCTTGGTT
TCAAAAATACTATTCTCCACATTTACAAAAACCAGAACTGGTTTGGAGAGAAATGCTTCCTCAGCTTGCTCACAATAGCCAAGAACGTCTTGAAAAAAAC
AAAAACTTTGAGATTTTTGTCCAACACTTGAAAAAAACAAACAAACAGGATCGATCGTTTGGAAGCAACGATCTGCAAATGGAAGAAAGTGTGAACATCG
TTAAGGATATGATCCTTCTAAAATCTATATCATAA
SEQ ID 123:
MSTVPVVQGAGSSNSAQDISTRPLTLKERISNLLSSTAFKVGLVVIGLLLVIATLIFLVSAASFVNAIYLVAIPAILGCVNICVGILSMEGHCSPERWIL
CKKVLKTSEDIIDDGQINNSNKVFTDERLNAIGGVVESLSRRNSLVDQTQ
SEQ ID 124:
ATGAGCACTGTACCCGTTGTTCAAGGAGCTGGATCTTCCAATTCGGCACAGGATATTTCCACTAGACCATTAACACTGAAAGAGCGTATATCGAATCTTC
TATCTTCCACTGCATTTAAGGTGGGATTAGTGGTGATAGGACTACTTTTAGTGATTGCTACTTTGATATTCCTAGTTTCGGCAGCTTCGTTTGTAAATGC
CATCTATCTAGTAGCTATTCCTGCTATTTTGGGATGCGTGAATATCTGCGTAGGAATTTTATCCATGGAAGGACACTGTTCTCCGGAGAGATGGATCTTA
TGTAAGAAGGTATTAAAGACTTCAGAAGATATCATCGATGATGGGCAGATAAACAACTCTAATAAAGTGTTTACTGATGAGAGGTTGAATGCCATAGGTG
GGGTAGTGGAATCTCTATCTAGAAGAAATAGTCTGGTGGATCAGACCCAATGA
SEQ ID 125:
MRIGDPMNKLIRRAVTIFAVTSVASLFASGVLETSMAESLSTNVISLADTKAKDNTSHKSKKARKNHSKETPVDRKEVAPVHESKATGPKQDSCFGRMYT
VKVNDDRNVEITQAVPEYATVGSPYPIEITATGKRDCVDVIITQQLPCEAEFVRSDPATTPTADGKLVWKIDRLGQGEKSKITVWVKPLKEGCCFTAATV
CACPEIRSVTKCGQPAICVKQEGPENACLRCPVVYKINIVNQGTATARNVVVENPVPDGYAHSSGQRVLTFTLGDMQPGEHRTITVEFCPLKRGRATNIA
TVSYCGGHKNTASVTTVINEPCVQVSIAGADWSYVCKPVEYVISVSNPGDLVLRDVVVEDTLSPGVTVLEAAGAQISCNKVVWTVKELNPGESLQYKVLV
RAQTPGQFTNNVVVKSCSDCGTCTSCAEATTYWKGVAATHMCVVDTCDPVCVGENTVYRICVTNRGSAEDTNVSLMLKFSKELQPVSFSGPTKGTITGNT
VVFDSLPRLGSKETVEFSVTLKAVSAGDARGEAILSSDTLTVPVSDTENTHIY
SEQ ID 126:
ATGCGAATAGGAGATCCTATGAACAAACTCATCAGACGAGCAGTGACGATCTTCGCGGTGACTAGTGTGGCGAGTTTATTTGCTAGCGGGGTGTTAGAGA
CCTCTATGGCAGAGTCTCTCTCTACAAACGTTATTAGCTTAGCTGACACCAAAGCGAAAGACAACACTTCTCATAAAAGCAAAAAAGCAAGAAAAAACCA
CAGCAAAGAGACTCCCGTAGACCGTAAAGAGGTTGCTCCGGTTCATGAGTCTAAAGCTACAGGACCTAAACAGGATTCTTGCTTTGGCAGAATGTATACA
GTCAAAGTTAATGATGATCGCAATGTTGAAATCACACAAGCTGTTCCTGAATATGCTACGGTAGGATCTCCCTATCCTATTGAAATTACTGCTACAGGTA
AAAGGGATTGTGTTGATGTTATCATTACTCAGCAATTACCATGTGAAGCAGAGTTCGTACGCAGTGATCCAGCGACAACTCCTACTGCTGATGGTAAGCT
AGTTTGGAAAATTGACCGCTTAGGACAAGGCGAAAAGAGTAAAATTACTGTATGGGTAAAACCTCTTAAAGAAGGTTGCTGCTTTACAGCTGCAACAGTA
TGCGCTTGTCCAGAGATCCGTTCGGTTACAAAATGTGGACAACCTGCTATCTGTGTTAAACAAGAAGGCCCAGAGAATGCTTGTTTGCGTTGCCCAGTAG
TTTACAAAATTAATATAGTGAACCAAGGAACAGCAACAGCTCGTAACGTTGTTGTTGAAAATCCTGTTCCAGATGGTTACGCTCATTCTTCTGGACAGCG
TGTACTGACGTTTACTCTTGGAGATATGCAACCTGGAGAGCACAGAACAATTACTGTAGAGTTTTGTCCGCTTAAACGTGGTCGTGCTACCAATATAGCA
ACGGTTTCTTACTGTGGAGGACATAAAAATACAGCAAGCGTAACAACTGTGATCAACGAGCCTTGCGTACAAGTAAGTATTGCAGGAGCAGATTGGTCTT
ATGTTTGTAAGCCTGTAGAATATGTGATCTCCGTTTCCAATCCTGGAGATCTTGTGTTGCGAGATGTCGTCGTTGAAGACACTCTTTCTCCCGGAGTCAC
AGTTCTTGAAGCTGCAGGAGCTCAAATTTCTTGTAATAAAGTAGTTTGGACTGTGAAAGAACTGAATCCTGGAGAGTCTCTACAGTATAAAGTTCTAGTA
AGAGCACAAACTCCTGGACAATTCACAAATAATGTTGTTGTGAAGAGCTGCTCTGACTGTGGTACTTGTACTTCTTGCGCAGAAGCGACAACTTACTGGA
AAGGAGTTGCTGCTACTCATATGTGCGTAGTAGATACTTGTGACCCTGTTTGTGTAGGAGAAAATACTGTTTACCGTATTTGTGTCACCAACAGAGGTTC
TGCAGAAGATACAAATGTTTCTTTAATGCTTAAATTCTCTAAAGAACTGCAACCTGTATCCTTCTCTGGACCAACTAAAGGAACGATTACAGGCAATACA
GTAGTATTCGATTCGTTACCTAGATTAGGTTCTAAAGAAACTGTAGAGTTTTCTGTAACATTGAAAGCAGTATCAGCTGGAGATGCTCGTGGGGAAGCGA
TTCTTTCTTCCGATACATTGACTGTTCCAGTTTCTGATACAGAGAATACACACATCTATTAA
SEQ ID 127:
MKKTALLAALCSVVSLSSCCRIVDCCFEDPCAPIQCSPCESKKKDVDGGCNSCNGYVPACKPCGGDTHQDAKHGPQARGIPVDGKCRQ
SEQ ID 128:
ATGAAAAAAACTGCTTTACTCGCTGCTTTATGTAGTGTTGTTTCTTTAAGTAGTTGTTGTCGTATCGTTGACTGTTGCTTCGAAGATCCATGCGCACCTA
TCCAATGTTCACCTTGTGAATCTAAGAAGAAAGACGTAGACGGTGGTTGCAACTCTTGTAACGGGTATGTCCCAGCTTGCAAACCTTGCGGAGGGGATAC
GCACCAAGATGCTAAACATGGCCCTCAAGCTAGAGGAATTCCAGTTGACGGCAAATGCAGACAATAG
SEQ ID 129:
MPKIDTCDSCVSNTELLAIRTRVTQSYNEAQTILSSIPDGIFLLSESGEILICNPQARAILGIPEDIQLVTRMFHDFFPDTFFGFSVQEALEKEVPPKTI
RLTLSQELSQKEVEVFVRKNISHDFLFLLIRDRSDYRQLEQAIEKYRSISELGKLAATLAHEIRNPLTSISGFATLLKEELSSERHQRMLNVIIEGTRSL
NSLVSSMLEYTKIQPLNLRSIDLQDFFSSLIPELSLTFPSCTFRRTILSPIQRSIDPDRLRCVIWNLVKNAVEASDEEIFLELHEKGFSVINTGTLPPNI
QEKLFIPFFTTKPQGNGLGLAEAHKIMRLHGGDLVVSTQDNRTTFTILWTPA
SEQ ID 130:
ATGCCAAAAATCGACACTTGTGATTCTTGCGTTTCCAATACCGAACTTTTGGCCATTCGTACGCGAGTAACACAATCGTATAACGAAGCTCAAACCATCC
TATCTTCGATTCCCGATGGCATTTTTCTACTTTCTGAATCTGGAGAGATTCTGATTTGCAATCCCCAAGCCCGCGCTATTTTAGGCATCCCTGAGGACAT
CCAGCTGGTCACACGGATGTTCCATGATTTTTTCCCCGATACTTTTTTTGGATTCTCAGTACAAGAAGCTTTAGAAAAAGAAGTCCCTCCTAAAACGATT
CGACTAACCCTATCTCAAGAACTCTCCCAAAAAGAGGTAGAAGTTTTTGTTAGGAAAAATATCTCTCACGACTTCCTCTTCCTTCTCATCCGCGACCGGT
CGGACTATAGGCAATTAGAACAAGCGATTGAAAAATACCGCAGCATTTCCGAGTTAGGGAAAATAGCTGCAACTCTAGCACATGAAATCCGTAATCCTCT
AACTAGTATTTCAGGATTCGCAACCTTACTGAAAGAAGAGCTCTCTTCAGAACGCCACCAACGCATGCTCAATGTCATCATAGAAGGTACTCGCTCATTA
AATTCTCTTGTTTCTTCTATGCTTGAATATACAAAAATTCAACCTCTGAACCTTCGTTCTATAGACCTACAGGATTTCTTTTCTTCTCTCATTCCAGAAC
TCTCTTTAACCTTTCCTTCTTGTACATTTAGAAGAACCATCTTATCTCCTATACAGCGCTCTATAGATCCTGATCGCTTGCGATGTGTGATATGGAACCT
TGTAAAAAATGCCGTCGAAGCATCGGATGAAGAAATCTTTCTAGAACTACATGAAAAAGGGTTTTCCGTTATCAATACCGGCACTCTTCCTCCTAATATC
CAAGAAAAGCTTTTTATTCCTTTCTTCACTACGAAACCTCAAGGGAACGGTCTAGGCCTAGCAGAGGCTCATAAAATCATGCGCCTGCATGGCGGAGATC
TGGTTGTTTCAACCCAGGATAATCGTACTACCTTTACCATCCTATGGACTCCCGCTTAA
SEQ ID 131:
MFTSLSAIQNAIRPSCQLPVLTPRRALITSLASGIILGLAGCVVGVLASFPALIAVSAVILGVSLFASGLFLCRYVCPPKIVSRRPSTELPAEPTPELPE
IKRPKPIAPPPPDFIPPRPLRRTIGEMLFGWNCIGSIRQMPFFLANDKTPLSFRNPSARFRAWNIPSTHTIFVSTSGQFSSLRMQSNLPAAIANATQSAA
FAKRGQGGLGVNDAFPAVLTDKCWEESKPDSGILLPGECSSATWEDKNHLVPCWDEETKTYNKPLLFIQMLAPKASMYQDDSKSCYEITLRAYTACFEEA
IRCGCRIIQIPLIAAFGDFVPRALSKQPKWIESAKLSLLHAVEKTAKKHASKDLVIVLTNIPQPVNL
SEQ ID 132:
ATGTTTACGTCGCTGTCCGCAATACAGAATGCTATACGTCCTTCTTGTCAACTTCCTGTTTTGACTCCTAGACGCGCTCTCATTACTTCTCTTGCGTCTG
GAATCATTTTAGGACTTGCTGGTTGCGTGGTTGGCGTTTTAGCCTCCTTTCCTGCCCTAATCGCCGTTTCTGCTGTTATTTTAGGTGTCAGTCTTTTTGC
TTCAGGACTATTTCTCTGTCGATATGTTTGTCCCCCAAAAATTGTGTCCCGAAGACCTTCTACCGAACTCCCTGCTGAACCTACTCCCGAGCTGCCTGAA
ATCAAAAGACCTAAACCTATAGCTCCTCCTCCTCCAGATTTCATACCTCCAAGACCACTGAGAAGAACGATCGGTGAAATGCTTTTTGGATGGAACTGCA
TAGGATCGATAAGACAGATGCCGTTTTTCCTTGCTAATGACAAAACGCCTCTGTCCTTCAGAAATCCTTCAGCAAGATTTAGAGCCTGGAATATTCCTTC
CACTCATACTATTTTTGTCTCTACTTCAGGCCAATTTTCTTCTTTGAGAATGCAATCGAATCTACCTGCTGCGATTGCAAATGCCACGCAATCGGCAGCC
TTCGCGAAGAGAGGCCAAGGAGGATTAGGAGTGAACGATGCATTCCCTGCTGTGCTTACCGACAAGTGCTGGGAAGAATCGAAACCCGACTCAGGCATCC
TACTTCCAGGAGAATGCTCTTCTGCCACCTGGGAAGACAAAAATCATCTAGTGCCTTGCTGGGATGAGGAAACAAAGACCTATAACAAGCCTCTATTGTT
CATCCAAATGCTAGCTCCTAAAGCTTCTATGTATCAAGATGACTCTAAATCTTGCTATGAGATAACCTTACGAGCTTACACAGCTTGTTTCGAAGAGGCT
ATTCGTTGTGGTTGTCGTATAATCCAAATTCCTTTAATCGCTGCTTTCGGAGATTTTGTTCCAAGAGCGCTAAGCAAACAGCCAAAATGGATCGAGTCTG
CTAAACTATCCTTACTCCATGCCGTAGAAAAAACCGCGAAAAAACACGCATCCAAAGATCTAGTGATTGTTTTAACGAACATCCCTCAACCCGTGAATTT
ATAA
SEQ ID 133:
MEKRGVIVHILVCLLTIFGTFSLPAFGAHFLAEEEQFYMDRFVFSGQYPDMETMEIHAERKKRVQFDVTGSFPKLESVVYKGSFGLLRSKIKGECPELSS
VNLSCTSCRMDLDFRGEWKKNASIYIRNEQEPITIMLPKDIGVVVYTQVDMNSKVVAEGSLIKRGRGFWKKTFRNSLVGESPVTLTFHVETRNGGVIFLR
SEQ ID 134:
ATGGAGAAGAGAGGCGTTATTGTGCATATACTAGTTTGTTTGTTGACAATCTTCGGAACGTTCAGTTTACCCGCTTTCGGCGCGCATTTTCTCGCGGAAG
AAGAGCAGTTTTATATGGATCGGTTTGTTTTCTCTGGGCAGTATCCAGATATGGAAACTATGGAAATCCATGCAGAAAGAAAAAAACGTGTACAATTTGA
TGTGACGGGAAGCTTCCCTAAGTTGGAGAGCGTGGTTTATAAGGGATCTTTTGGATTGCTGCGTTCGAAAATAAAGGGAGAGTGTCCAGAACTGTCTTCT
GTAAATCTTTCTTGTACCTCCTGCAGAATGGATTTAGATTTTCGAGGGGAGTGGAAAAAGAATGCGTCTATTTATATTCGTAATGAGCAAGAGCCAATTA
CAATTATGTTGCCTAAAGACATTGGTGTAGTTGTCTATACGCAGGTTGATATGAATAGTAAAGTAGTTGCAGAGGGATCACTAATCAAGAGAGGAAGAGG
TTTTTGGAAGAAAACTTTTCGGAATTCTTTGGTAGGAGAATCCCCTGTGACGCTAACTTTTCATGTAGAGACTCGTAATGGAGGAGTTATTTTTCTCCGT
TAG
SEQ ID 135:
MQTSRISSFFRGLVHLYRWAISPFLGAPCRFFPTCSEYALVALKKHPLRKSLFLIAKRLLKCGPWCIGGIDLVPRTSVEEYLSSPTPLAESPDDRTVPHT
QETS
SEQ ID 136:
ATGCAAACTTCCCGGATCAGCTCTTTTTTCCGAGGGCTTGTTCACCTGTACCGTTGGGCGATTTCTCCTTTTCTCGGGGCTCCTTGTCGCTTTTTCCCTA
CATGCTCTGAGTACGCTCTTGTTGCACTAAAGAAACATCCGCTCAGAAAAAGCCTTTTTCTCATCGCCAAGCGCTTACTCAAATGCGGCCCTTGGTGCAT
AGGAGGTATCGATCTCGTCCCTAGAACTTCTGTTGAAGAATATCTCAGTTCCCCTACCCCTCTAGCAGAATCCCCAGACGACAGGACTGTGCCACACACC
CAAGAAACTTCTTAG
SEQ ID 137:
MKRLFFICALALSPLAYGAVQKDPMLMKETFRNNYGIIVSKQEWNKRGCDGSITRVFKDGTTTLEVYAQGALHGEVTRTFPHSTTLAVIETYDQGRLLSK
KTFFPNALPAKEEVYHEDGSFSLTRWPDNNNSDTITDPCFVEKTYGGRVLEGHYTSFNGKYSSTILNGEGVRSTFSSDSILLTEESFNDGVMVKKTTFYS
TREPETVTHYVNGYPHGVRFTYLPGGIPNTIEEWRYGHQDGLTILFKNGCKIAEVPFVRGAKNGIELRYNEQENIAEEISWQHNILHGVRKIHAAGVCKS
EWYYKGKPVSQIKFERLSAAR
SEQ ID 138;
ATGAAGCGTTTATTTTTTATCTGCGCCCTCGCCCTTTCTCCTCTAGCATATGGAGCTGTTCAAAAGGATCCTATGTTAATGAAGGAGACTTTCCGTAATA
ACTACGGGATCATTGTCTCTAAGCAAGAATGGAACAAACGTGGATGCGATGGCTCCATCACTAGAGTATTCAAAGATGGAACTACAACCTTAGAAGTTTA
TGCGCAAGGTGCTTTACATGGGGAAGTCACACGAACGTTTCCTCACTCTACTACCCTGGCCGTTATAGAAACTTATGATCAGGGAAGGCTTCTTTCTAAG
AAGACCTTCTTCCCAAATGCTTTGCCTGCTAAAGAAGAAGTTTACCACGAAGATGGGTCTTTCTCCCTAACACGTTGGCCTGACAATAACAACTCTGACA
CAATCACAGACCCCTGCTTTGTAGAAAAAACTTATGGGGGAAGAGTATTGGAAGGTCATTACACCTCTTTTAATGGAAAATACTCTTCAACAATCCTTAA
CGGCGAGGGAGTTCGCTCTACTTTTTCTTCGGATAGTATCTTGTTGACAGAAGAGTCGTTTAATGATGGCGTAATGGTCAAAAAAACGACATTTTACTCG
ACTCGAGAACCCGAAACCGTCACTCATTATGTCAATGGGTACCCTCACGGAGTTCGGTTTACCTATCTTCCTGGTGGGATTCCAAATACGATTGAAGAAT
GGCGATATGGACATCAAGACGGCCTTACAATCTTATTTAAAAATGGTTGTAAGATTGCTGAAGTCCCATTTGTACGCGGAGCAAAAAATGGAATCGAACT
CCGATACAATGAACAAGAGAATATCGCTGAAGAGATTTCTTGGCAGCAGAACATCTTGCATGGAGTCCGTAAAATCCATGCGGCGGGGGTATGCAAATCC
GAATGGTATTACAAAGGCAAACCTGTCTCGCAAATCAAGTTTGAACGACTCAGCGCTGCCAGATAA
SEQ ID 139:
MKEPQTSYQRFFRAYNRRALPSIALKFFIGLMLIGIYAPLFASSKPILVRWHGEWYFPLFRYLLFPGFYTKSIDLFFNVLMLTLPFFILGFRYLSGVWKK
LFLGVVTGIHIAVFSFALSGRVQDPCRDELLKQKRAKHLQQELKTTPKTEFLPTIAKRTRTWESERAYMSKYEQLGMLVKAKYRKMQHDHLEKQREAYEL
CKQSPMPTLRFLEMKNETASLRFLKNKINKLKPSYPEGFEGWGTLLEDYRPYFMARARSEHALNMAIYEQHPQEELRAAFEALEEKEAPFREQLAFVRSL
LEEREALNNSIAFIMDKRNWIETESEQVQMVLNPLLSSFHWEDDAGGSREMNKYVHWWQLTRINRKDLLASLIFGIRIAIVVGGLGVSIALFIGIIVGLL
SGYFGGKVDMLLSRVTEIWETMPMLFILMLVVAITQKKSLILDSVLLGCFGWVSISRYVRIETLKQRNLGYVLAATNLCYSHYHIMVHQILPNVIVPVIS
LLPFSMMAMISCEAGLTFLGLGEESSASWGNLLREGVTAFPSESAILWPPAIMLTLLLMAIAVIGDGIRDALDPKMQD
SEQ ID 140:
ATGAAGGAACCCCAAACATCTTATCAACGATTTTTTCGTGCTTATAATAGACGGGCACTTCCCTCTATAGCTTTAAAGTTCTTTATTGGACTTATGCTTA
TTGGTATTTACGCTCCTTTATTTGCTTCTAGTAAACCGATTCTTGTTCGTTGGCACGGGGAGTGGTATTTCCCCTTGTTCCGTTATTTGCTTTTCCCAGG
TTTTTACACTAAGTCTATCGATTTATTTTTTAATGTCTTAATGCTCACACTGCCGTTTTTTATTTTAGGCTTTCGTTATCTCAGTGGTGTGTGGAAAAAG
CTGTTTCTAGGTGTAGTGACTGGAATACATATTGCGGTATTCTCTTTTGCTTTGAGTGGGAGAGTTCAAGATCCTTGTCGGGATGAGCTGTTAAAGCAGA
AACGGGCTAAGCATCTGCAACAGGAATTGAAAACAACTCCAAAGACAGAGTTTCTTCCAACAATTGCTAAAAGAACACGCACTTGGGAAAGTGAGCGTGC
TTATATGAGTAAATATGAGCAGCTGGGAATGCTTGTAAAAGCCAAATATCGCAAGATGCAGCACGATCATCTTGAAAAACAAAGGGAGGCATACGAGTTG
TGTAAGCAATCTCCGATGCCGACTCTGCGTTTTCTAGAAATGAAGAACGAAACAGCAAGCCTGCGTTTTCTCAAAAATAAGATCAACAAGTTAAAACCTT
CCTATCCGGAAGGTTTTGAAGGATGGGGAACTTTGCTGGAAGATTACCGTCCTTATTTCATGGCTAGAGCACGTTCAGAACATGCTCTGAATATGGCGAT
ATACGAGCAACATCCCCAAGAAGAGTTGCGTGCAGCGTTTGAGGCTCTTGAGGAAAAAGAGGCTCCTTTTAGAGAGCAGTTGGCCTTTGTACGTAGTCTT
TTAGAAGAGCGTGAAGCTTTAAATAATTCGATTGCGTTTATCATGGATAAGCGTAATTGGATAGAAACCGAGTCTGAACAGGTACAAATGGTTTTGAATC
CATTATTAAGCAGCTTTCACTGGGAAGATGATGCCGGCGGATCTCGAGAGATGAACAAGTATGTGCATTGGTGGCAGCTTACACGCATTAATAGAAAGGA
TTTACTCGCTTCTCTGATCTTTGGGATTCGTATTGCGATCGTTGTTGGTGGATTGGGTGTTTCTATAGCTTTATTTATAGGCATCATTGTGGGATTGTTA
TCTGGCTACTTTGGTGGCAAGGTAGACATGTTATTATCACGAGTGACAGAAATTTGGGAGACTATGCCCATGTTGTTTATTCTTATGCTCGTGGTAGCTA
TTACACAAAAAAAATCTCTCATATTAGATTCGGTATTGCTGGGATGTTTTGGATGGGTCAGTATTAGTCGCTATGTGCGTATAGAAACCTTAAAGCAAAG
GAATTTAGGGTATGTTCTAGCTGCTACCAACTTGTGCTACAGCCATTACCATATTATGGTGCATCAGATCCTTCCTAACGTGATTGTTCCGGTTATTTCT
TTATTGCCGTTCTCGATGATGGCTATGATTAGCTGTGAAGCAGGGCTCACTTTTTTAGGGTTAGGAGAGGAGAGTTCGGCATCTTGGGGAAATCTTTTGC
GAGAAGGAGTCACAGCATTTCCATCAGAGAGCGCCATTCTATGGCCTCCCGCTATTATGTTGACATTGTTGTTAATGGCTATTGCTGTGATTGGAGATGG
GATTCGGGATGCGTTAGATCCTAAGATGCAGGATTAA
SEQ ID 141:
MIDKIIRTILVLSLFLLYWSSDLLEKDVKSIKRELKALHEDVLELVRISHQQKNWVQSTDFSVSPEISVLKDCGDPAFPNLLCEDPYVEKVVPSLLKEGF
VPKGILRTAQVGRPDNLSPFNGFVNIVRFYELCVPNLAVEHVGKYEEFAPSLALKIEEHYVEDGSGDKEFHIYLRPNMFWEPIDPTLFPKNITLADSFLR
PHPVTAHDVKFYYDVVMNPYVAEMRAVAMRSYFEDMVSVRVENDLKLIVRWRAHTVRNEQGEEEKKVLYSAFANTLALQPLPCFVYQHFANGEKIVPEDS
DPDTYRKDSVWAQNFSSHWAYNYIVSCGAFRFAGMDDEKITLVRNPNYHNPFAALVEKRYIYMKDSTDSLFQDFKAGKVDIAYFPPNHVDNLASFMQTSA
YKEQAARGEAILEKNSSDRSYSYIGWNCLSLFFNNRSVRQAMNMLIDRDRIIEQCLDGRGVSVSGPFSLCSPSYNRDVEGWQYSPEEAARKLEEEGWIDA
DGDGIREKVIDGVVVPFRFRLCYYVKSVTARTIAEYVATVCKEVGIECCLLGLDMADYSQALEEKNFDAILSGWCLGTPPEDPRALWHSEGALEKGSANA
VGFCNEEADRIIEQLSYEYDSNKRQALYHRFHEVIHEESPYAFLYSRQYSLVYKEFVKNIFVPTEHQDLIPGAQDETVNLSMLWVDKEEGRCSAIS
SEQ ID 142:
ATGATAGATAAAATTATACGAACAATACTGGTTCTGTCCTTATTCCTGTTGTATTGGTCTTCAGATCTACTTGAAAAAGATGTGAAATCGATCAAAAGAG
AACTCAAGGCTTTACATGAAGATGTTCTTGAGTTAGTCCGGATCTCGCATCAGCAAAAAAATTGGGTCCAGTCTACAGATTTTTCTGTTTCTCCAGAGAT
CAGTGTATTGAAGGATTGCGGAGATCCTGCGTTCCCTAATTTATTATGCGAAGACCCTTATGTTGAAAAAGTGGTCCCTTCGTTGTTAAAGGAAGGTTTT
GTTCCGAAAGGTATTTTGCGTACAGCTCAAGTAGGAAGGCCTGATAACCTAAGTCCGTTTAATGGCTTTGTTAATATCGTTCGATTTTATGAATTGTGCG
TTCCTAATTTGGCTGTTGAGCATGTTGGTAAATACGAGGAGTTTGCGCCTAGTTTAGCCTTAAAGATAGAAGAGCATTATGTAGAGGATGGGTCTGGGGA
TAAAGAATTTCATATTTATTTGCGTCCTAATATGTTTTGGGAGCCGATAGATCCTACGCTGTTCCCTAAAAATATAACTTTAGCAGACAGCTTCTTAAGA
CCACATCCTGTCACCGCTCATGATGTGAAGTTCTATTACGATGTAGTCATGAATCCCTATGTTGCAGAAATGCGTGCAGTGGCTATGAGATCTTATTTTG
AGGATATGGTTTCGGTTCGGGTAGAAAACGATTTGAAATTAATCGTTCGTTGGAGAGCTCATACTGTACGTAATGAACAGGGAGAGGAAGAGAAAAAAGT
GCTCTATTCTGCTTTCGCGAATACATTGGCACTCCAACCGTTACCTTGTTTCGTGTATCAGCATTTCGCAAATGGAGAGAAGATCGTTCCAGAAGATTCT
GATCCCGATACGTATCGCAAAGATTCGGTATGGGCGCAAAACTTTTCTTCACATTGGGCGTATAATTACATAGTGAGCTGTGGAGCATTCCGATTTGCAG
GGATGGATGATGAGAAAATTACTTTAGTTCGTAATCCTAATTATCATAATCCGTTTGCGGCTCTTGTGGAGAAGCGCTATATCTATATGAAAGATAGTAC
AGATTCTCTCTTCCAAGATTTCAAAGCTGGGAAGGTGGATATTGCGTATTTCCCTCCTAACCATGTCGATAATCTAGCGAGCTTCATGCAAACCTCTGCT
TATAAGGAACAAGCTGCTAGAGGAGAGGCAATTTTAGAAAAAAATTCATCAGACCGGTCCTATTCTTACATCGGATGGAATTGTCTTTCTCTTTTCTTTA
ACAATCGTTCGGTACGACAAGCCATGAATATGTTGATCGATCGGGATCGCATTATTGAGCAGTGCTTGGATGGTCGTGGAGTCTCTGTGAGTGGGCCTTT
TTCTCTCTGCTCTCCATCATACAACAGAGATGTAGAGGGATGGCAATACTCTCCGGAAGAGGCCGCACGTAAATTAGAGGAAGAGGGCTGGATCGATGCT
GATGGAGATGGTATTCGTGAGAAAGTAATCGATGGAGTTGTAGTGCCTTTCCGTTTCCGGTTATGCTACTATGTGAAAAGTGTAACAGCACGAACGATTG
CCGAATATGTAGCTACGGTATGTAAAGAGGTGGGTATCGAGTGTTGCTTACTCGGGTTAGATATGGCGGATTATTCACAAGCCCTCGAGGAGAAAAATTT
CGATGCTATTCTTTCCGGATGGTGTTTAGGAACCCCTCCAGAAGATCCTCGTGCTCTATGGCATTCGGAAGGAGCTTTGGAGAAAGGATCTGCCAATGCT
GTTGGATTTTGTAATGAGGAAGCAGACCGTATCATCGAACAGCTCAGTTACGAGTATGATTCTAATAAGCGCCAAGCCTTGTATCACCGTTTTCACGAGG
TGATTCATGAGGAATCTCCTTACGCGTTTCTCTATTCAAGACAGTACTCCCTTGTCTATAAGGAGTTTGTAAAAAATATTTTTGTGCCAACAGAACATCA
GGATTTGATTCCTGGAGCTCAAGATGAGACAGTGAATTTATCCATGTTGTGGGTAGATAAAGAGGAGGGTCGATGCTCCGCTATATCTTAA
SEQ ID 143:
MIRGSSLISEVRVKFKYLRPLSFLVLVIVAFCYGCSREKQEILVGRDATWFPQQFGIYTSGINAFVNDLVSEINYKEGLNISIVNQDWVHLFENLDDKKT
SGAFTSASPSIEMLARYQFSDPVLLTGPVLVVLENSPYHSLQDLEGKLIGVTKFDSSVLIAQNVPNAVIDSYQHIPVALEALSTQRYDALLVPVIEATAL
VETAYKGRLRIASEPLNEEGLRLVVLRGGGSDSLLEGFNAGLAKIRRSGRYKAIKMQSRLP
SEQ ID 144:
ATGATTCGGGGATCTAGTCTGATCTCTGAGGTTAGAGTGAAATTTAAGTATTTGCGTCCATTAAGCTTTTTAGTCTTGGTTATTGTAGCGTTTTGCTACG
GATGTTCCAGAGAGAAACAAGAGATTCTCGTCGGAAGGGATGCTACTTGGTTCCCTCAACAATTTGGTATTTATACATCAGGAATTAACGCCTTTGTGAA
TGATTTAGTTTCTGAGATCAATTACAAGGAAGGGTTGAATATCTCTATAGTGAACCAAGATTGGGTTCATCTTTTTGAGAATTTAGATGATAAGAAGACT
AGCGGAGCCTTTACTTCAGCCTCTCCTTCAATAGAAATGTTAGCTCGGTACCAGTTTTCAGATCCCGTTTTATTAACCGGGCCTGTGCTTGTTGTTTTAG
AAAATTCTCCGTATCATTCTCTCCAGGATTTAGAAGGAAAGTTGATCGGAGTATATAAATTCGATTCATCCGTTCTTATTGCACAGAATGTTCCCAATGC
TGTGATTGATTCCTATCAGCATATTCCTGTAGCCTTAGAAGCTTTGTCTACTCAGCGTTATGATGCGTTATTGGTGCCTGTAATAGAGGCAACTGCTTTA
GTAGAAACGGCTTATAAAGGACGTTTGCGAATCGCTTCAGAACCTCTTAATGAGGAAGGTTTGCGTTTAGTTGTGTTACGAGGAGGAGGATCGGATTCCC
TATTGGAAGGATTTAATGCAGGATTGGCAAAAATTCGTCGATCAGGAAGATACAAAGCCATTAAAATGCAATCCCGGCTTCCTTAG
SEQ ID 145:
MKNFFRFLLKGFLSVCGLFLGVIGAAGFIFVLSASVLGAGDGVLFVNFPNAQGVVQELGKTAPIIAVIDINDAIMASGGAAKRLQSALQPLNEAPYKGRV
KGILVKIDCPGGEVFEIDRMCATLSFWKKQWGIPVHVFVSGLCASGGYYVACIADKIGTTSSSLIGSIGVRSGPYFSVKEGLQRHGVETAILTAGDDKAP
LNPFSSWTEEEYAERQGIVDAFYEQFVDHVVKYRSKLSKEKLTKVLGARVFIAKQALEEGLVDAINQTQEQALEELAEACGIKDNYRVIGLGSGHFLKRF
SSYLSNSPLVTGKLQVTALPDQQQKSLWYMG
SEQ ID 146:
ATGAAGAATTTTTTTCGATTTTTATTAAAAGGTTTTTTATCTGTCTGCGGTTTGTTTTTAGGTGTGATAGGAGCTGCCGGATTCATTTTTGTCCTATCGG
CCTCTGTTCTTGGGGCGGGAGACGGAGTTTTGTTTGTCAACTTCCCCAACGCTCAAGGAGTTGTTCAAGAGCTTGGGAAAACTGCTCCCATTATTGCAGT
GATTGATATTAACGATGCTATTATGGCTAGCGGTGGCGCTGCAAAGCGTTTACAATCCGCTTTACAGCCTTTAAATGAAGCTCCTTACAAAGGAAGAGTA
AAAGGGATCTTAGTCAAAATAGATTGTCCTGGTGGTGAGGTTTTTGAAATTGATCGGATGTGCGCAACACTCTCTTTCTGGAAGAAACAGTGGGGAATCC
CTGTCCACGTCTTTGTATCTGGACTCTGTGCTTCCGGAGGATATTATGTTGCTTGTATTGCCGATAAAATTGGAACCACTTCGAGTTCTCTGATTGGTTC
AATAGGAGTACGTTCGGGCCCATATTTTAGTGTTAAAGAAGGCTTACAACGACATGGCGTGGAAACTGCTATTCTTACAGCGGGAGATGACAAAGCGCCG
TTAAATCCTTTTTCTTCATGGACAGAGGAAGAGTACGCCGAGCGCCAGGGGATAGTGGATGCTTTCTATGAACAGTTTGTGGATCATGTTGTTAAATATC
GTTCGAAGCTGTCTAAGGAAAAACTAACGAAGGTTTTGGGAGCCCGTGTATTTATTGCGAAGCAAGCTCTGGAAGAAGGGTTGGTGGATGCGATCAATCA
AACTCAAGAACAAGCTTTAGAAGAACTGGCTGAAGCCTGTGGTATCAAAGACAATTATCGAGTCATTGGGTTGGGTTCTGGCCATTTTTTAAAACGTTTT
TCTAGCTATCTAAGTAATAGCCCGCTTGTAACAGGGAAACTCCAAGTGACGGCTTTACCTGATCAGCAACAAAAATCTTTGTGGTACATGGGTTGA
SEQ ID 147:
MFKLVSYIILSWVLVCLAQPDVSVVASVVSCICGYSLLWAGLFALVEQLSWKKVWCIAFIWTWTVEGAHFSWMLEDLYVGTSIYFVWGILLSYLATLFAS
FSCLVVWCCRKQYRGALVWLPGVWVAIEAIRYYGLLSGVSFDFIGWPLTATAYGRQFGSFFGWAGQSFLVIAANICCFAVCLLKHSFSKGLWLTLCAFPY
LLGGAHYEYLKKHFSDSEVLRVAIVQPGYSPHMHAGRTASAIWRGLVSLCQTIQTPVDVIVFPEVSVPFGLHRQAYTLHENQPVLESLLPNKSWGEFFTN
LDWIQAIAERYQCTVIMGMERWENKGGILHLYNAAECVSREGEITSYDKRILVPGGEYIPGGKIGFSLCQTFFPEFALPFQRLPGEFSGVVNITERIKAG
ISICYEETFGYAIRPYKRQQADILVNLTNDGWYPRSRLPLVHFYHGMLRNQELGIPCIRACRTGVSAAVDSLGRIVGILPWESRTCPVSTGVLQVSVPLY
SYHTVYARLGDAPLLLIAVCSVIGAIAYFYRKKKETPPQTFF
SEQ ID 148:
GTGTTTAAACTTGTGTCATACATCATCCTTTCTTGGGTGCTGGTCTGTTTGGCTCAGCCGGATGTAAGTGTTGTAGCTTCTGTTGTTAGTTGTATTTGCG
GTTACAGCTTACTTTGGGCTGGGCTTTTTGCTTTAGTAGAGCAATTATCTTGGAAGAAAGTTTGGTGCATCGCTTTTATTTGGACTTGGACTGTCGAAGG
CGCTCATTTCTCTTGGATGCTTGAAGATCTTTATGTAGGGACAAGCATCTATTTTGTTTGGGGTATACTGCTTTCTTATCTCGCCACCCTATTTGCTAGT
TTTTCTTGTTTGGTTGTGTGGTGTTGTCGCAAGCAATATAGGGGAGCTCTTGTTTGGCTTCCAGGGGTTTGGGTGGCGATAGAAGCAATACGCTATTATG
GGTTGCTTTCAGGAGTTTCTTTTGATTTTATTGGCTGGCCTCTTACAGCGACAGCCTATGGCCGGCAATTCGGCAGCTTTTTTGGATGGGCTGGACAAAG
CTTTCTAGTTATTGCTGCCAATATATGCTGTTTTGCAGTATGTTTATTAAAACACTCTTTTTCCAAAGGTTTGTGGTTGACGTTGTGCGCGTTCCCTTAT
CTGTTAGGCGGAGCGCATTACGAATACCTAAAGAAGCATTTTTCCGACTCTGAAGTGCTTCGAGTTGCCATCGTGCAGCCTGGATATAGTCCTCATATGC
ATGCAGGGAGGACGGCTAGTGCTATTTGGAGAGGTTTGGTTTCTTTGTGCCAGACTATTCAAACTCCTGTAGATGTGATCGTTTTCCCAGAAGTAAGTGT
TCCTTTTGGCTTACATAGACAAGCCTATACTCTTCATGAAAATCAGCCTGTATTAGAAAGTTTGCTTCCTAACAAATCTTGGGGCGAGTTTTTCACAAAT
TTGGATTGGATCCAAGCGATAGCTGAACGTTATCAATGCACCGTTATCATGGGAATGGAACGATGGGAAAATAAAGGGGGAATACTGCATTTGTATAATG
CTGCTGAATGCGTATCGCGAGAAGGGGAAATAACTAGCTATGATAAGCGGATTCTTGTTCCTGGAGGTGAGTACATCCCTGGAGGGAAAATAGGTTTTTC
CTTGTGTCAAACCTTTTTCCCAGAATTTGCTCTTCCCTTTCAACGTTTGCCAGGAGAGTTTTCTGGAGTTGTGAATATAACAGAGCGAATAAAAGCTGGG
ATCTCTATTTGTTATGAGGAGACATTTGGGTATGCAATTCGCCCTTACAAAAGGCAACAAGCCGATATTTTAGTAAATCTTACTAATGACGGTTGGTATC
CGCGTTCAAGGCTGCCTCTAGTACATTTTTATCATGGCATGTTACGTAATCAAGAGTTGGGTATACCTTGTATTCGCGCCTGTCGCACAGGAGTTTCTGC
TGCAGTGGATTCTTTGGGTAGAATTGTCGGCATACTTCCCTGGGAATCGAGAACTTGCCCAGTTTCTACAGGAGTACTCCAAGTTTCCGTCCCTCTTTAC
AGTTATCATACTGTATATGCAAGGCTGGGTGATGCTCCTCTGTTACTGATTGCAGTTTGTTCGGTTATCGGAGCGATTGCCTATTTTTATAGGAAAAAGA
AAGAGACCCCACCACAAACATTTTTTTGA
SEQ ID 149:
MKNILSWMLMFAVALPIVGCDNGGGSQTSATEKSMVEDSALTDNQKLSRTFGHLLSRQLSRTEDFSLDLVEVIKGMQSEIDGQSAPLTDTEYEKQMAEVQ
KASFEAKCSENLASAEKFLKENKEKAGVIELEPNKLQYRVVKEGTGRVLSGKPTALLHYTGSFIDGKVFDSSEKNKEPILLPLTKVIPGFSQGMQGMKEG
EVRVLYIHPDLAYGTAGQLPPNSLLIFEVKLIEANDDNVSVTE
SEQ ID 150:
ATGAAGAATATATTAAGTTGGATGCTTATGTTTGCAGTCGCTCTGCCTATCGTAGGATGTGATAACGGAGGCGGTTCGCAAACATCGGCTACGGAGAAAA
GCATGGTAGAAGACTCTGCATTGACAGACAATCAAAAGTTATCAAGAACTTTTGGGCATTTATTGTCTCGTCAGTTGAGCCGAACGGAAGATTTTTCGTT
AGATCTTGTTGAAGTGATTAAAGGGATGCAATCTGAAATAGATGGACAGAGTGCTCCTTTAACAGACACAGAATATGAAAAACAAATGGCAGAAGTACAA
AAAGCTAGTTTCGAAGCAAAATGCTCGGAAAATTTAGCTTCTGCAGAAAAATTCTTAAAAGAAAATAAAGAGAAGGCTGGGGTTATTGAGTTAGAGCCTA
ATAAGTTACAGTACCGTGTTGTGAAAGAGGGTACAGGACGGGTTCTTTCTGGGAAGCCTACAGCTTTGCTTCACTATACAGGGAGCTTCATCGATGGGAA
GGTTTTTGATTCTTCAGAGAAGAATAAAGAGCCCATTTTACTGCCTTTGACCAAAGTAATTCCTGGATTTTCCCAAGGTATGCAAGGTATGAAAGAAGGA
GAGGTTCGAGTTCTTTACATACATCCAGATTTAGCTTACGGAACAGCTGGACAATTACCTCCAAACTCTCTACTCATTTTTGAAGTGAAGTTAATTGAAG
CAAACGACGATAATGTATCTGTTACAGAATAG
SEQ ID 151:
MKVILRALCLFLVLPCGCYARVPSFEPFRGAIAPNRYTPKHSPELYFEMGDKYFQAKKFKQALLCFGMITHHFPEHALHPKAQFLVGLCYLEMGHPDLAD
KALTQYQELADTEYSEQLFAIKYSIAQSFANGKRKNIVPLEGFPKLLKADTDALRIFEEIVTASSDADLKASALYAKGALLFDRKEYSEAIKTLKKVSLQ
FPSHSLSPESFTLIAKIHCLQALQEPYNEQYLQDARMNAAALRKQHPNHPSNTEVENYIHHMCEAYASCLYSTGRFYEKKRKASSAKIYYSIALENFPDT
SYVAKCNKRLERLSKQMS
SEQ ID 152:
ATGAAAGTCATTTTAAGAGCGCTTTGCTTGTTTCTTGTGTTGCCCTGCGGATGTTATGCACGAGTGCCCTCTTTTGAACCTTTCCGAGGCGCTATCGCCC
CAAACCGGTACACTCCTAAACATTCCCCAGAACTCTATTTCGAGATGGGAGATAAATACTTTCAGGCTAAAAAATTTAAGCAAGCTCTTCTTTGTTTTGG
AATGATAACACATCATTTCCCAGAACATGCTCTTCATCCTAAAGCACAGTTTCTTGTAGGGCTCTGCTATCTTGAAATGGGCCATCCTGACTTAGCAGAT
AAAGCGCTAACTCAATATCAAGAGCTCGCCGATACAGAATATTCTGAACAATTATTCGCCATTAAGTATTCTATCGCACAAAGTTTCGCTAACGGAAAAC
GTAAAAATATCGTTCCTTTGGAAGGGTTTCCTAAGTTGTTGAAAGCAGATACAGATGCTCTGCGTATTTTTGAAGAAATTGTGACAGCATCTTCCGACGC
AGACCTCAAAGCTTCTGCTCTCTACGCAAAAGGTGCTCTTTTGTTCGACCGAAAAGAATATTCGGAAGCGATCAAAACTCTAAAAAAAGTTTCTCTTCAG
TTTCCTTCACACTCTCTTTCTCCAGAGTCTTTTACCCTTATTGCAAAAATCCATTGCTTACAAGCTTTGCAAGAGCCCTATAATGAACAGTATCTTCAAG
ATGCTCGGATGAATGCAGCAGCTTTACGTAAACAACACCCTAATCATCCTAGCAATACAGAAGTAGAGAACTATATTCATCACATGTGCGAAGCTTACGC
TTCTTGCTTATATTCAACCGGACGCTTTTATGAGAAAAAGCGAAAAGCCTCTTCTGCAAAAATTTATTACTCAATAGCTCTAGAAAACTTCCCTGATACC
TCCTATGTTGCTAAATGCAATAAACGATTAGAACGGCTCTCTAAACAAATGAGTTAA
SEQ ID 153:
MLKMFWLNSLVFFSLLLSACGYTVLSPHYVEKKFSLSEGIYVCPIEGDSLGDLVSSLSYELEKRGLHTRSQGTSSGYVLKVSLFNETDENIGFAYTPQKP
DEKPVKHFIVSNEGRLALSAKVQLIKNRTQEILVEKCLRKSVTFDFQPDLGTANAHQLALGQFENHNEAIKSASRILYSQLAETIVQQVYYDLF
SEQ ID 154:
ATGCTGAAAATGTTTTGGTTGAATAGCCTCGTTTTCTTCTCGTTACTACTATCAGCCTGCGGCTATACAGTGCTCTCCCCCCACTATGTAGAAAAGAAAT
TCTCGCTTTCCGAAGGCATCTATGTCTGCCCTATCGAAGGAGATTCATTAGGAGATCTCGTATCCTCTCTTTCTTACGAATTAGAAAAGCGAGGACTCCA
CACACGATCTCAAGGAACCTCTTCTGGTTATGTACTCAAAGTCTCTCTTTTCAATGAGACTGATGAAAATATTGGATTCGCATACACTCCCCAAAAACCT
GATGAAAAACCTGTAAAACACTTCATTGTCTCTAATGAAGGGCGCTTAGCGTTATCAGCAAAAGTCCAACTAATCAAAAACCGCACACAAGAAATATTAG
TGGAGAAATGCCTGAGAAAATCGGTTACTTTTGATTTTCAACCTGACCTCGGAACCGCGAATGCTCATCAGCTAGCTCTCGGACAATTTGAAATGCATAA
TGAAGCAATAAAAAGCGCTTCTCGTATATTGTATTCGCAATTAGCAGAGACTATTGTACAACAGGTATACTATGACCTTTTCTGA
SEQ ID 155:
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMIDGILWEGFGGDPCDPCATWCDAISMRVGYYGDFVFDRVLKTDVNKEFQMGAKPTTDTGNSAAPST
LTARENPAYGRHMQDAEMFTNAACMALNIWDRFDVFCTLGATSGYLKGNSASFNLVGLFGDNENQKTVKAESVPNMSFDQSVVELYTDTTFAWSVGARAA
LWECGCATLGASFQYAQSKPKVEELNVLCNAAEFTINKPKGYVGKEFPLDLTAGTDAATGTKDASIDYHEWQASLALSYRLNMFTPYIGVKWSRASFDAD
TIRIAQPKSATAIFDTTTLNPTIAGAGDVKTGAEGQLGDTMQIVSLQLNKMKSRKSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRF
SEQ ID 156:
ATGAAAAAACTCTTGAAATCGGTATTAGTATTTGCCGCTTTGAGTTCTGCTTCCTCCTTGCAAGCTCTGCCTGTGGGGAATCCTGCTGAACCAAGCCTTA
TGATCGACGGAATTCTGTGGGAACGTTTCGGCGGAGATCCTTGCGATCCTTGCGCCACTTGGTGTGACGCTATCAGCATGCGTGTTGGTTACTACGGAGA
CTTTGTTTTCGACCGTGTTTTGAAAACTGATGTGAATAAAGAATTTCAGATGGGTGCCAAGCCTACAACTGATACAGGCAATAGTGCAGCTCCATCCACT
CTTACAGCAAGAGAGAATCCTGCTTACGGCCGACATATGCAGGATGCTGAGATGTTTACAAATGCCGCTTGCATGGCATTGAATATTTGGGATCGTTTTG
ATGTATTCTGTACATTAGGAGCCACCAGTGGATATCTTAAAGGAAACTCTGCTTCTTTCAATTTAGTTGGATTGTTTGGAGATAATGAAAATCAAAAAAC
GGTCAAAGCGGAGTCTGTACCAAATATGAGCTTTGATCAATCTGTTGTTGAGTTGTATACAGATACTACTTTTGCGTGGAGCGTCGGCGCTCGCGCAGCT
TTGTGGGAATGTGGATGTGCAACTTTAGGAGCTTCATTCCAATATGCTCAATCTAAACCTAAAGTAGAAGAATTAAACGTTCTCTGCAATGCAGCAGAGT
TTACTATTAATAAACCTAAAGGGTATGTAGGTAAGGAGTTTCCTCTTGATCTTACAGCAGGAACAGATGCTGCGACAGGAACTAAGGATGCCTCTATTGA
TTACCATGAATGGCAAGCAAGTTTAGCTCTCTCTTACAGACTGAATATGTTCACTCCCTACATTGGAGTTAAATGGTCTCGAGCAAGCTTTGATGCCGAT
ACGATTCGTATAGCCCAGCCAAAATCAGCTACAGCTATTTTTGATACTACCACGCTTAACCCAACTATTGCTGGAGCTGGCGATGTGAAAACTGGCGCAG
AGGGTCAGCTCGGAGACACAATGCAAATCGTTTCCTTGCAATTGAACAAGATGAAATCTAGAAAATCTTGCGGTATTGCAGTAGGAACAACTATTGTGGA
TGCAGACAAATACGCAGTTACAGTTGAGACTCGCTTGATCGATGAGAGAGCAGCTCACGTAAATGCACAATTCCGCTTCTAA
SEQ ID 157:
MNIVTSKIGSKILRIIQNNKKLGLLSALVVLDAALLSVNSRSSEGLIGQSASLPNYHETEQQIAACPKNIAKNLAKKSSPGSKPTVGASFPSQPVSVKAA
PAKPQTPVAQTRHFKKSHQIFSPNFTQSPQQVNKPEERRRPLESRYLQGAVKQAAAAKEKKALEQEVSKQEEEASKLWEEKQSYARRAVNAINFSVRKQI
EEQQKTISNPGNDQTLPRKKDPQTSGEPVIQTVQDCSQDQEEEKKVLERLNKRSLTCQDLKEVEYTVNFEDISILELLQFVSKISGTNFVFDSNDLQFNV
TIVSHDPTSVDDLATILLQVLKMHDLKVVEQGNNVLIYRNPKLSKLSTVVTDGSAKDTCEAVVVTRVFRLYSVSPSAAVGIIQPLLSHDAIISASESTRH
IIVSDIAGNIEKVRELLQALDSPGTAIDMSEYDVQFANPAALVSYCQDVLGAMAEEEAFQIFIQPGTNKIFVISSPRLTAKTIQLLESLDIPEMAHTLDD
VTSPAAALGSSGAANPKSLRFFMYKLKYQNGAAIAQAIQDIGYNLYVTTAMDEDFINTLNSIQWLPVNNSIVVIGNQANVDKVVSLLNGLDLPPKQVYIE
VLILETSLEKSWDFGVQWAALGDEQGKVAYASGLLSNTGLTDPLRNQSLPVAPNPGNISLPTPGQLAGISDMMYGSSAFGLGIIGNVLSHNGKSYLTLGG
LLSALDQDGDTTVVLNPRIMAQDTQQASFFVGQTIPFQTTSTVIQETGSVTQNIEYEDIGVNLVVTSTIAPNNVVTLQIEQTISELHSAQGVLTPVTDKT
FAATRLQVPDGCFLVMSGHIRDKLTKIVSGVPLLSSLPLIKGLFSRSIDQRQKRNIMIFIKPKVISSFEEGTALSNTEGYRYNWESERGSLEVAPRHAPE
CQHIPKVQAESDFKMLEIEAE
SEQ ID 158:
GTGAACATAGTGACGTCGAAAATAGGAAGCAAGATTTTAAGAATCATTCAAAATAACAAGAAATTAGGCCTCTTGTCTGCGTTAGTTGTTCTAGATGCGG
CGTTGTTAAGTGTGAATTCACGATCTAGCGAAGGCTTAATAGGCCAATCCGCTTCTTTGCCGAATTATCATGAGACAGAACAGCAGATCGCTGCTTGTCC
TAAAAATATTGCTAAGAATTTAGCAAAGAAAAGCTCTCCGGGGTCTAAACCTACAGTAGGAGCTTCATTTCCTTCACAGCCAGTTTCCGTGAAGGCAGCT
CCTGCAAAGCCACAAACTCCTGTTGCACAAACACGGCATTTTAAAAAGAGCCATCAGATTTTCTCTCCTAATTTTACACAGTCTCCCCAACAGGTTAATA
AACCTGAGGAAAGAAGACGTCCTTTGGAGTCTCGGTATTTACAAGGTGCGGTTAAGCAGGCAGCTGCTGCAAAGGAAAAGAAGGCTCTTGAACAGGAAGT
ATCCAAACAAGAAGAAGAGGCATCTAAACTCTGGGAAGAGAAGCAAAGTTATGCTCGTCGTGCAGTTAATGCCATCAATTTCAGTGTAAGAAAGCAGATA
GAAGAGCAACAGAAAACCATTTCCAATCCAGGAAATGACCAGACTCTTCCTAGGAAGAAAGATCCGCAGACATCTGGAGAACCTGTTATCCAAACGGTAC
AAGACTGTTCTCAGGATCAAGAAGAAGAGAAAAAAGTTTTAGAGCGATTAAATAAACGTTCTCTGACGTGTCAGGATCTGAAAGAAGTTGAATATACCGT
CAATTTTGAGGACATTTCTATCTTAGAATTGCTCCAGTTTGTCAGTAAGATCTCAGGAACGAATTTCGTTTTCGATAGCAATGACTTGCAATTCAATGTC
ACTATCGTTTCTCATGATCCTACTTCCGTGGATGATTTAGCAACGATTCTATTGCAAGTCTTGAAAATGCATGACTTGAAAGTCGTTGAACAAGGAAATA
ATGTATTGATCTACCGCAATCCTAAGCTTTCCAAGCTTTCTACGGTGGTTACAGATGGATCAGCAAAAGATACTTGTGAGGCTGTAGTAGTTACACGAGT
ATTTCGCTTGTACAGCGTCAGTCCTTCCGCTGCGGTAGGCATTATTCAACCGCTGCTCTCTCATGATGCAATTATTAGTGCTTCCGAGTCTACGAGACAC
ATTATCGTATCAGATATAGCAGGAAATATTGAGAAAGTCCGGGAGTTATTGCAAGCATTGGATAGCCCAGGCACCGCTATTGACATGTCGGAATATGATG
TGCAGTTTGCAAATCCCGCTGCTTTGGTCAGCTATTGTCAGGATGTTCTCGGTGCCATGGCTGAGGAAGAGGCTTTTCAAATTTTTATTCAGCCTGGGAC
CAATAAAATTTTTGTTATTTCCTCGCCACGATTAACAGCAAAGACAATTCAATTATTGGAGTCCTTGGACATTCCAGAAATGGCACATACGCTAGACGAT
GTCACAAGTCCTGCTGCTGCTTTGGGAAGCTCTGGAGCTGCTAATCCTAAGAGTTTGCGCTTCTTCATGTACAAATTAAAATATCAAAATGGGGCAGCTA
TCGCTCAGGCGATTCAAGATATTGGATACAATCTATACGTGACAACAGCAATGGATGAGGATTTCATCAACACATTGAATAGTATTCAATGGTTGCCTGT
AAACAACTCCATCGTTGTCATTGGAAATCAAGCTAACGTCGATAAGGTCGTTAGCTTGCTAAATGGGTTGGACCTCCCTCCAAAACAAGTGTACATTGAA
GTATTGATTCTAGAGACAAGCTTAGAGAAGTCTTGGGACTTCGGAGTACAATGGGCGGCTCTTGGAGATGAACAAGGGAAGGTGGCATATGCTTCCGGAT
TGTTGAGTAATACAGGATTAACGGATCCCCTTCGTAATCAATCTCTACCTGTAGCACCAAACCCAGGGAATATCTCATTGCCAACACCCGGTCAGTTAGC
AGGGATCAGTGATATGATGTACGGATCCTCTGCATTTGGACTAGGAATTATTGGAAACGTTCTCAGCCATAATGGGAAATCGTATTTAACATTAGGGGGG
TTATTGAGCGCCTTAGATCAAGATGGGGATACCACAGTGGTACTTAACCCTAGAATTATGGCGCAAGATACACAACAGGCATCGTTCTTTGTAGGACAAA
CGATTCCGTTCCAGACTACGAGTACAGTGATTCAGGAAACCGGATCTGTTACACAAAATATTGAATACGAAGATATCGGAGTCAATCTTGTTGTAACTTC
GACAATAGCTCCTAATAACGTAGTAACTTTACAAATCGAGCAAACGATTTCTGAGTTGCATTCGGCACAAGGAGTGCTGACTCCTGTAACAGATAAAACA
TTTGCAGCTACGAGACTACAAGTGCCGGATGGATGTTTCCTCGTCATGAGTGGGCATATTCGTGATAAACTGACAAAAATTGTATCCGGAGTGCCGTTAC
TCAGTTCTCTTCCTCTGATCAAAGGACTCTTTAGTCGGTCTATCGATCAGCGTCAGAAACGGAATATTATGATTTTCATTAAGCCGAAAGTCATCAGTAG
CTTCGAGGAAGGAACAGCGTTATCAAACACAGAAGGATATCGTTATAACTGGGAAAGCGAAAGAGGATCTTTAGAGGTAGCCCCTCGTCATGCCCCTGAA
TGCCAACATATTCCTAAGGTCCAAGCAGAAAGTGATTTTAAAATGCTGGAAATAGAAGCGGAATAA
SEQ ID 159:
MGIRLVIDKGPLSGTVLILENGTSWSLGSDGKASDILLQDEKLAPSQIRITLKDGEYYLENLDALRPVSVDGTVITAPVLLKDGVSFVMGSCQVSFFKGE
EVEGDIELSFQTEGGNEGEPAAQGSSSVSSEAPKKETGNPSLPSEAKASGEVSSSAIAKEQELAASFLASVEKEPGTPKEVSEPKVSSQEGQTPSVTGEK
KDLELPLASQEQPKQTTPSGSGEPTQSQNASMEENRTSPDQNQQPQLSSASESGSQSPENQEQQPSQTPPPSPETPEPSGEPNSATEENSPSPMEKASVT
EEGSSGTSEEEKEGEEDTAESAANEEPKAEASQEEEKKEEDKGEVLAPFNVQDLFRFDQGIFPAEIEDLAQKQVAVDLTQPSRFLLKVLAGANIGAEFHL
DSGKTYIVGSDPQVADIVLSDMSISRQHAKIIIGNDNSVLIEDLGSKNGVIVEGRKIEHQSTLSANQVVALGTTLFLLVDYAAPSDTVMATISSEDYGLF
GRPQSPEEIAARAAEEEEEKRKRATLPTGAFILTLFIGGLALLFGIGTASLFHTKEVVSIDQIDLIHDIEHVIQQFPTVRFTFNKNNGQLFLIGHVRNSI
DKSELLYKVDALSFVKSVDDNVIDDEAVWQEMNILLSKNPEFKGISMQSPEPGIFVISGYLKTEEQAACLADYLNLHFNYLSLLDNKVIIESQVMKALAG
HLVQSGFANVHVSFTNGEAVLTGYINNKDADKFRTVVQELQDIAGIRAVKNFVVLLPAEEGVIDLNMRYPGRYRVTGFSKCGDISINVVVNGRILTRGDI
LDGMTVTSIQSHCIFLEREGLKYKIEYNK
SEQ ID 160:
ATGGGTATACGCTTAGTTATTGATAAAGGGCCCTTGTCTGGAACTGTTCTTATTTTAGAAAATGGGACGAGTTGGTCTCTTGGCAGTGATGGAAAAGCTA
GTGATATTCTCCTGCAAGATGAAAAGCTTGCTCCCTCTCAGATTCGCATCACTTTAAAAGATGGCGAGTATTATTTAGAAAATTTAGATGCTTTGAGGCC
GGTTTCTGTTGATGGAACAGTTATCACTGCCCCTGTTTTGTTAAAAGATGGGGTTTCCTTTGTAATGGGAAGCTGCCAAGTCTCGTTTTTTAAAGGGGAA
GAGGTAGAAGGAGATATAGAGTTATCGTTCCAGACAGAAGGTGGTAATGAGGGAGAGCCTGCAGCGCAAGGCTCTTCAAGCGTTTCGTCCGAAGCTCCTA
AAAAGGAGACAGGGAATCCAAGTCTTCCTTCGGAGGCAAAGGCTTCTGGAGAAGTATCTAGTTCAGCAATAGCGAAAGAACAAGAGTTAGCGGCGTCCTT
TTTAGCTTCTGTTGAGAAGGAGCCTGGAACACCAAAAGAAGTCTCTGAGCCAAAGGTCTCTTCACAAGAAGGACAGACTCCTTCTGTTACAGGAGAAAAA
AAGGATCTTGAGCTTCCTTTGGCAAGTCAAGAACAACCTAAACAAACTACTCCATCAGGCAGTGGTGAACCAACCCAATCTCAAAACGCGAGTATGGAAG
AAAACAGAACGTCGCCCGATCAAAATCAGCAGCCACAGCTTTCTTCTGCTTCAGAATCGGGTTCTCAAAGTCCCGAAAATCAGGAGCAACAACCTTCTCA
AACGCCTCCCCCATCCCCGGAAACTCCAGAGCCGTCAGGAGAACCTAATAGCGCTACGGAAGAAAACTCGCCATCTCCAATGGAGAAAGCTTCCGTAACA
GAAGAAGGCAGCTCAGGGACGAGTGAAGAAGAAAAAGAGGGTGAAGAAGATACTGCTGAAAGCGCAGCAAATGAAGAGCCAAAGGCAGAGGCTTCTCAAG
AAGAAGAGAAGAAAGAGGAAGATAAAGGAGAGGTTCTTGCTCCCTTTAATGTTCAGGATCTTTTCCGTTTTGATCAAGGAATCTTCCCTGCTGAGATAGA
AGATCTTGCACAGAAACAAGTTGCGGTTGATTTGACGCAACCATCACGATTTTTGTTGAAGGTTCTTGCTGGTGCGAATATCGGTGCTGAATTCCATTTG
GATAGTGGGAAAACCTATATCGTAGGAAGTGATCCGCAGGTTGCAGACATTGTCTTAAGTGATATGAGTATTTCGCGCCAACATGCGAAGATCATTATCG
GAAATGATAATTCAGTTTTGATTGAAGATCTGGGTAGTAAGAATGGCGTGATTGTTGAAGGGCGCAAGATTGAACATCAATCTACGCTCTCTGCGAATCA
AGTTGTTGCTCTAGGAACAACGTTATTCTTACTTGTCGACTATGCTGCTCCTTCCGATACGGTAATGGCGACGATTTCTTCTGAAGATTATGGGTTATTT
GGTCGTCCGCAATCTCCTGAAGAGATTGCTGCCAGAGCTGCGGAAGAGGAAGAAGAGAAGAGAAAACGTGCTACGTTGCCAACAGGTGCTTTTATATTAA
CCTTGTTCATTGGAGGGTTAGCTCTGCTCTTTGGAATAGGAACAGCTTCTTTGTTCCATACGAAGGAAGTAGTTTCTATAGATCAAATCGATTTGATTCA
TGATATTGAACATGTAATTCAGCAGTTTCCAACTGTACGGTTTACGTTCAATAAGAACAACGGACAGTTGTTCTTAATTGGGCATGTAAGAAATAGCATT
GATAAGAGCGAGTTACTTTACAAAGTGGATGCTCTCTCGTTTGTCAAGTCGGTAGATGATAACGTGATCGATGACGAGGCAGTATGGCAAGAGATGAATA
TTCTCTTGTCTAAGAATCCAGAATTTAAAGGTATCAGCATGCAATCTCCAGAGCCGGGGATTTTTGTAATCAGCGGGTATCTAAAGACAGAAGAACAAGC
AGCTTGTTTGGCTGATTATCTAAATCTACATTTTAATTACCTTTCACTATTGGATAATAAGGTGATTATCGAATCACAAGTCATGAAAGCTCTTGCTGGA
CATCTTGTGCAATCAGGTTTTGCGAACGTTCATGTGTCCTTCACCAATGGTGAAGCTGTTTTGACAGGATATATCAATAATAAAGATGCAGATAAATTCC
GAACGGTTGTGCAAGAACTGCAAGATATTGCAGGGATTCGTGCGGTGAAGAATTTTGTCGTTTTGCTGCCTGCAGAAGAAGGTGTTATTGATCTAAATAT
GCGGTATCCAGGCCGTTATCGGGTAACCGGTTTTTCAAAGTGCGGGGATATTAGTATTAATGTTGTAGTTAATGGGCGTATTTTAACTCGAGGCGATATT
TTAGATGGAATGACGGTAACAAGCATTCAATCGCATTGTATCTTTTTAGAACGGGAAGGGTTGAAATATAAAATTGAGTACAATAAATAG
SEQ ID 161:
MESGPESVSSNQSSMNPIINGQIASNSETKESTKESEASPSASSSVSSWSFLSSAKHALISLRDAILNKNSSPTDSLSQLEASTSTSTVTRVAARDYNEA
KSNFDTAKSGLENATTLAEYETKMADLMAALQDMERLAKQKAEVTRIKEALQEKQEVIDKLNQLVKLEKQNQTLKETLTTTDSADQIPAINSQLEINKNS
ADQIIKDLEGQNISYEAVLTNAGEVIKASSEAGIKLGQALQSIVDAGDQSQAAVLQAQQNNSPDNIAATKKLIDAAETKVNELKQEHTGLTDSPLVKKAE
EQISQAQKDIQEIKPSGSDIPIVGPSGSAASAGSAVGALKSSNNSGRISLLLDDVDNEMAAIAMQGFRSMIEQFNVNNPATAKELQAMEAQLTAMSDQLV
GADGELPAEIQAIKDALAQALKQPSTDGLATAMGQVAFAAAKVGGGSAGTAGTVQMNVKQLYKTAFSSTSSSSYAAALSDGYSAYKTLNSLYSESRSGVQ
SAISQTANPALSRSVSRSGIESQGRSADASQRAAETIVRDSQTLGDVYSRLQVLDSLMSTIVSNPQVNQEEIMQKLTASISKAPQFGYPAVQNSADSLQK
FAAQLEREFVDGERSLAESRENAFRKQPAFIQQVLVNIASLFSGYLS
SEQ ID 162:
ATGGAATCAGGACCAGAATCAGTTTCTTCTAATCAGAGCTCGATGAATCCAATTATTAATGGGCAAATCGCTTCTAATTCGGAGACCAAAGAGTCCACGA
AGGAGTCAGAAGCGAGTCCTTCAGCATCGTCCTCTGTAAGCAGCTGGAGTTTTTTATCCTCAGCAAAGCATGCATTAATCTCTCTTCGTGATGCCATCTT
GAATAAAAATTCTAGTCCAACAGACTCTCTCTCTCAATTAGAGGCCTCTACTTCTACCTCTACGGTTACACGTGTAGCTGCGCGAGATTATAATGAGGCT
AAATCGAATTTTGATACGGCGAAAAGTGGATTAGAGAACGCTACGACACTTGCTGAATACGAGACGAAAATGGCTGATTTAATGGCAGCTCTCCAAGATA
TGGAGCGTTTGGCTAAACAGAAGGCTGAAGTTACAAGAATTAAAGAAGCTCTTCAAGAGAAACAAGAGGTTATTGATAAGCTCAATCAGTTAGTTAAACT
TGAAAAACAGAATCAGACTTTAAAGGAAACTTTAACAACCACAGACTCTGCAGATCAGATTCCAGCGATTAATAGTCAGTTAGAGATCAACAAAAATTCT
GCAGATCAAATTATCAAAGATCTGGAAGGACAAAACATAAGTTATGAAGCTGTTCTCACTAACGCAGGAGAGGTTATCAAAGCTTCTTCTGAAGCGGGAA
TTAAGTTAGGACAAGCTTTGCAGTCTATTGTGGATGCTGGGGATCAAAGCCAGGCTGCAGTTCTTCAAGCACAGCAAAATAATAGCCCAGATAATATCGC
AGCCACGAAGAAATTAATTGATGCTGCTGAAACGAAGGTAAACGAGTTAAAACAAGAGCATACAGGGCTAACGGACTCGCCTTTAGTGAAAAAAGCTGAG
GAGCAGATTAGTCAAGCACAAAAAGATATTCAAGAGATCAAACCTAGTGGTTCGGATATTCCTATCGTTGGTCCGAGTGGGTCAGCTGCTTCCGCAGGAA
GTGCGGTAGGAGCGTTGAAATCCTCTAACAATTCAGGAAGAATTTCCTTGTTGCTTGATGATGTAGACAATGAAATGGCAGCGATTGCAATGCAAGGTTT
TCGATCTATGATCGAACAATTTAATGTAAACAATCCTGCAACAGCTAAAGAGCTACAAGCTATGGAGGCTCAGCTGACTGCGATGTCAGATCAACTGGTT
GGTGCGGATGGCGAGCTCCCAGCCGAAATACAAGCAATCAAAGATGCTCTTGCGCAAGCTTTGAAACAACCATCAACAGATGGTTTAGCTACAGCTATGG
GACAAGTGGCTTTTGCAGCTGCCAAGGTTGGAGGAGGCTCCGCAGGAACAGCTGGCACTGTCCAGATGAATGTAAAACAGCTTTACAAGACAGCGTTTTC
TTCGACTTCTTCCAGCTCTTATGCAGCAGCACTTTCCGATGGATATTCTGCTTACAAAACACTGAACTCTTTATATTCCGAAAGCAGAAGCGGCGTGCAG
TCAGCTATTAGTCAAACTGCAAATCCCGCGCTTTCCAGAAGCGTTTCTCGTTCTGGCATAGAAAGTCAAGGACGCAGTGCAGATGCTAGCCAAAGAGCAG
CAGAAACTATTGTCAGAGATAGCCAAACGTTAGGTGATGTATATAGCCGCTTACAGGTTCTGGATTCTTTGATGTCTACGATTGTGAGCAATCCGCAAGT
AAATCAAGAAGAGATTATGCAGAAGCTCACGGCATCTATTAGCAAAGCTCCACAATTTGGGTATCCTGCTGTTCAGAATTCTGCGGATAGCTTGCAGAAG
TTTGCTGCGCAATTGGAAAGAGAGTTTGTTGATGGGGAACGTAGTCTCGCAGAATCTCGAGAGAATGCGTTTAGAAAACAGCCCGCTTTCATTCAACAGG
TGTTGGTAAACATTGCTTCTCTATTCTCTGGTTATCTTTCTTAA
SEQ ID 163:
MKKYFYKGFVGALLLACGSTNLAFAQASSMDSQLWSVEDLDSYLSSKGFVETRKRDGVLRLAGDVRARWIYAKEDLETTQTPAKPMLPTNRYRSEFNLYV
DYTAANSWMTSKMNWVTIAGGESSAAGLDINRAFLGYRFYKNPETQAEVFAEIGRSGLGDIFDSDVQFNSNFDGIHLYAARRISEKLPFTMIVHGGPFVV
NMAEKEYAWVVEAILNKLPGNFVVKTSVVDWNTLTAKTNDPADASAAQPAKPNTKYDYLVWQWLVGKSTAMPWFNGQTKNLYTYGAYLFNPLAEIPENWK
QSTTPTTKITNGKENHAWFIGCSLGGVRRAGDWSATVRYEYVEALAIPEIDVAGIGRGNQMKYWFAQAIKQGLDPKESNGFTNYKGVSYQFVMGLTDSVS
FRAYAAYSKPANDNLGSDFTYRKYDLGLISSF
SEQ ID 164:
ATGAAAAAATACTTTTATAAAGGGTTTGTAGGCGCGCTTTTATTAGCTTGTGGGTCTACAAACTTGGCTTTTGCGCAGGCTAGTTCGATGGATAGCCAGC
TATGGTCTGTTGAAGATTTAGATTCTTATTTGAGTTCCAAAGGTTTTGTCGAGACTCGTAAGCGCGATGGAGTTCTACGTTTAGCTGGAGATGTCCGCGC
TCGATGGATTTATGCAAAAGAGGATCTTGAGACAACTCAGACTCCTGCTAAACCTATGTTACCTACCAATCGGTATCGTAGTGAATTCAATTTGTATGTG
GATTACACCGCTGCTAATAGTTGGATGACTTCGAAAATGAATTGGGTAACGATTGCTGGCGGAGAATCTTCTGCAGCAGGGTTAGATATTAATCGTGCCT
TCTTAGGATACCGATTCTACAAAAACCCAGAAACGCAAGCAGAAGTATTTGCAGAGATTGGTCGCTCTGGATTGGGAGATATTTTTGATTCCGACGTTCA
GTTTAATAGTAATTTCGACGGAATTCATTTATACGCTGCGCGACGTATTAGTGAGAAACTTCCTTTCACCATGATTGTTCATGGTGGTCCTTTTGTCGTG
AATATGGCAGAGAAAGAGTATGCTTGGGTCGTGGAAGCTATTTTGAATAAACTCCCAGGAAATTTCGTTGTGAAAACGAGTGTTGTTGACTGGAATACGT
TAACAGCAAAAACGAATGATCCAGCAGACGCAAGCGCTGCACAACCAGCTAAACCTAATACCAAGTACGATTATTTAGTATGGCAATGGTTGGTTGGGAA
GAGCACAGCTATGCCATGGTTTAATGGACAAACAAAAAATCTTTACACTTACGGAGCCTATCTCTTTAATCCATTAGCGGAAATACCAGAGAACTGGAAA
CAATCAACAACTCCTACAACCAAAATTACAAATGGTAAGGAAAACCATGCTTGGTTCATCGGCTGCTCTCTAGGCGGTGTTCGACGAGCTGGAGACTGGT
CTGCAACAGTTCGTTATGAGTATGTTGAAGCTTTAGCGATTCCAGAAATTGATGTCGCGGGTATTGGTCGCGGAAACCAAATGAAATATTGGTTTGCTCA
AGCTATCAAACAAGGATTGGATCCTAAAGAATCTAACGGCTTTACTAACTATAAAGGAGTTTCCTATCAGTTTGTTATGGGTCTGACAGATTCGGTTTCT
TTCCGAGCTTATGCTGCTTATTCTAAGCCTGCTAACGATAACCTTGGTAGCGACTTCACCTATCGTAAGTATGACCTAGGTTTAATTTCTTCATTCTAA
SEQ ID 165:
MRKDDEGSIVRSLFNLLSGTFFSRLTGMLREIVMATYFGADPLVASFWLAFRTIFFLRKLLGGPILGLAFIPHFEFLRAQNISRATFFFRSFSRFFCYSA
ILFTLIIELGLCVWCSCVTGSLFDTLLLTIILLPSGIFLMMYTVNSTLLHCEKKFFSVGLAPSVVNVSWIGTVFLARNYDPRNRIFGLAVVLVIGFILEW
AVTLPGVMKFLGQSKEVPQERDSIRALIAPLSLGLLSMGIFQLNLLCDMWLARYINEVGPLYLMYSVRIQQLPVHLFGLGVFTVLLPAISRCVQDQEHQQ
GYDLLRFSLKLTVAVMVVMTMGLLLFALPGVRVLYEHGVFPKTAVHAIVEVLRGYSGSIIPMALAPLVSALFYARRNYKVPMLVGIIAAVVNMVLNVIGC
LVCKQVAVLAYATSLVSWGQLAMLWYCAGKSLPTYKGIMWRTFKESGKTVITTILAAVITIGVNIVTHTTYVVFIEPLTVPTKPLVSFLDQCGVFFAESA
LFLSVLFGLAKLLKTEDLMNLISFQYWKGHQSILRN
SEQ ID 166:
ATGAGGAAAGATGATGAAGGATCGCTAGTGCGCTCATTGTTTAATTTGCTGTCCGGAACGTTTTTTAGTCGTCTTACTGGGATGTTACGAGAAATTGTTA
TGGCTACATATTTCGGAGCCGATCCCTTAGTAGCATCTTTTTGGCTGGCTTTTCGGACGATCTTTTTTTTAAGAAAGCTTTTAGGTGGGCCTATTCTTGG
ACTCGCTTTTATTCCGCATTTCGAGTTTTTACGTGCGCAAAATATTTCTCGAGCAACGTTTTTCTTTAGAAGCTTTTCGAGATTCTTTTGTTACAGCGCT
ATATTATTTACTTTAATTATAGAATTAGGACTCTGTGTTTGGTGTTCTTGCGTTACAGGAAGCCTATTTGATACCCTACTTTTAACAATCATACTGCTAC
CTTCCGGGATCTTTCTGATGATGTATACAGTGAATTCCACGCTGTTGCATTGTGAGAAGAAGTTTTTCAGCGTAGGACTTGCTCCTTCTGTTGTTAATGT
GTCGTGGATTGGAACGGTCTTTTTAGCACGGAATTATGATCCGAGGAATCGTATTTTTGGATTAGCTGTAGTCCTTGTTATAGGCTTCATTTTAGAATGG
GCTGTTACGCTTCCTGGAGTCATGAAGTTTTTGGGACAAAGTAAAGAGGTTCCTCAGGAGCGGGATAGTATCCGTGCTCTGATTGCCCCACTGTCTCTAG
GATTGTTATCCATGGGAATCTTTCAGTTGAACTTACTATGTGATATGTGGCTCGCGCGATATATCAATGAGGTAGGACCTCTGTATCTGATGTATTCCGT
GCGAATACAACAGTTACCTGTCCATTTATTTGGTCTTGGAGTCTTCACAGTGTTGCTACCTGCGATTTCTCGTTGCGTTCAAGATCAAGAACATCAACAA
GGATATGATCTCTTGCGGTTTTCGTTGAAGCTCACTGTTGCTGTTATGGTGGTTATGACGATGGGGCTATTGCTTTTTGCTTTGCCTGGGGTGCGAGTGT
TATATGAGCACGGAGTGTTTCCTAAAACAGCTGTGCACGCTATTGTAGAAGTTCTAAGGGGATATAGTGGAAGTATTATTCCTATGGCTTTAGCTCCTCT
CGTATCGGCTCTATTCTATGCAAGAAGGAATTACAAAGTTCCGATGCTGGTAGGGATCATTGCTGCCGTAGTGAATATGGTTCTTAATGTGATCGGATGT
TTAGTTTGCAAACAGGTTGCTGTTTTAGCCTACGCTACTTCTTTAGTGTCGTGGGGTCAGTTAGCGATGCTATGGTATTGTGCTGGTAAGAGTCTTCCTA
CTTACAAAGGATTGATGTGGAGAACGTTTAAAGAGAGTGGGAAAACTGTCATTACAACCATTCTAGCAGCGGTTATTACGATTGGTGTGAACATAGTAAC
GCATACCACGTACGTAGTATTTATCGAGCCATTAACAGTCCCAACAAAACCTTTAGTATCTTTTTTAGATCAGTGTGGAGTCTTTTTTGCAGAATCGGCA
CTTTTCTTATCAGTATTGTTTGGATTAGCTAAATTACTAAAGACAGAAGATCTTATGAATCTTATTTCTTTCCAATACTGGAAAGGGCATCAGTCTATCC
TAAGAAACTAG
SEQ ID 167:
MCVSRSLRWCLCFLLLCGWVDAGVYDKLRLTGINIIDRNGLSETICSKEKLQKYTKIDFLSPQPYQKVMRTYKNAAGESVACLTTYYPNGQIRQYLECLN
NRAFGRYREWHSNGKIHIQAEVIGGIADLHPSAEAGWLFDGTTYAHDSEGRLEAVIHYEKGLLEGISLYYHANGNVWKECPYHKGVAHGDFLVFTEEGSL
LKKQTFCKGQLSGCVLRYEPGSQSLLSEEEYKQGKLRSGKYYDPLTKEEIACVVNGKGKQVIYGKYAIIETRQIVHGVPHGEVLLFDEHGKSLLQAYSLI
NGQKEGEEVFFYPGGEGRKMLLTWSQGILQGAVKTWYPNGALESSKELVQNKKTGILMLYYPEGQVMATEEYVDDLLIKGEYFRPNDRYPYAKVEKGCGT
AVFFSATGGLLKKVLYEDGKPVIH
SEQ ID 168:
ATGTGTGTAAGTAGAAGCTTAAGATGGTGTTTATGTTTTCTTTTGCTGTGCGGATGGGTGGACGCTGGGGTTTATGATAAGCTCCGACTGACAGGCATTA
ACATTATCGATAGGAATGGTCTTTCTGAGACGATCTGTTCTAAAGAAAAATTACAAAAGTATACGAAAATCGATTTTCTCTCTCCTCAGCCTTACCAAAA
AGTCATGCGTACATACAAAAACGCAGCAGGCGAGTCGGTTGCTTGTTTAACGACGTACTATCCGAATGGCCAAATCCGACAATATCTCGAGTGTTTAAAT
AATCGTGCTTTTGGACGTTATCGTGAGTGGCATAGTAATGGCAAAATTCATATCCAGGCAGAAGTTATTGGAGGGATAGCAGATTTGCATCCTTCCGCAG
AAGCCGGATGGTTGTTCGATGGAACAACGTATGCACATGATAGCGAAGGGCGGTTAGAAGCTGTTATTCATTATGAAAAAGGCTTGCTGGAAGGGATTTC
GCTGTATTACCACGCGAATGGGAATGTATGGAAGGAATGTCCTTACCATAAAGGTGTTGCTCATGGAGACTTTTTGGTCTTCACCGAAGAAGGAAGTTTG
TTAAAGAAACAAACTTTTTGTAAAGGGCAGTTGTCTGGATGTGTATTACGCTACGAGCCAGGTTCACAGTCATTGTTGTCAGAAGAAGAATATAAACAAG
GGAAACTGCGCAGTGGTAAATATTACGATCCTCTTACTAAGGAAGAAATCGCGTGCGTAGTGAATGGCAAAGGTAAACAAGTAATTTATGGGAAATATGC
GATTATAGAGACCCGACAGATTGTACATGGCGTTCCTCACGGGGAAGTCTTGTTATTTGATGAACATGGTAAATCTCTGTTGCAAGCATATTCTCTAATC
AATGGGCAGAAAGAGGGAGAAGAAGTATTTTTCTATCCAGGCGGAGAAGGTAGAAAAATGTTATTAACATGGTCCCAAGGTATTCTACAAGGAGCTGTGA
AAACTTGGTACCCAAATGGCGCTTTGGAAAGTAGCAAAGAACTTGTTCAAAATAAAAAGACTGGGATTCTCATGCTATACTATCCCGAAGGACAAGTGAT
GGCTACCGAGGAATATGTAGACGATCTTCTCATAAAAGGAGAATATTTCCGGCCGAACGACCGATATCCATATGCTAAAGTGGAAAAAGGTTGTGGGACA
GCGGTCTTTTTCAGTGCTACAGGAGGACTGTTAAAGAAAGTCCTCTATGAAGATGGGAAGCCTGTTATTCATTAG
SEQ ID 169:
MRRLGVWVLLLLASGAASLPAIGAWCWRQRTAEAWENLLIDMRDFQSKRERSSQVAIKNARLKAAHKQASFPNWIAQGENLVFLNKERDALAKLPATAWV
VRSRAVKDRKAFLEDNRLSWQEQTLGEKSTLFSFQKELQIDDEDIPVLLGLFDPKYTQIPIVFLSYWEMTKQVSSLGNEVWVVHAEAWGRCV
SEQ ID 170:
ATGCGACGCTTAGGAGTATGGGTGCTGTTACTATTAGCGAGTGGGGCTGCTTCTCTTCCTGCAATAGGAGCATGGTGTTGGCGTCAGCGTACAGCAGAGG
CTTGGGAAAATTTACTCATCGATATGAGAGATTTTCAGTCTAAACGAGAGCGATCTTCTCAGGTAGCAATCAAGAATGCGCGGCTGAAAGCAGCGCATAA
ACAAGCGAGTTTCCCCAATTGGATTGCCCAAGGAGAGAATCTCGTTTTCTTGAATAAGGAGCGAGATGCTCTAGCTAAACTTCCTGCAACAGCCTGGGTG
GTGAGAAGTCGTGCAGTCAAGGATCGGAAGGCTTTCTTAGAAGATAACCGCTTGTCATGGCAGGAGCAGACTTTAGGAGAGAAAAGCACGCTGTTTTCTT
TCCAAAAAGAGCTCCAAATAGATGACGAGGACATTCCTGTATTATTAGGATTGTTTGATCCTAAGTATACCCAAATACCCATTGTTTTTCTTTCTTACTG
GGAAATGACGAAGCAGGTGTCATCATTAGGAAATGAGGTGTGGGTCGTTCACGCGGAGGCTTGGGGACGATGTGTGTAA
SEQ ID 171:
MKTICKLVILALLFPNVSYALVQVGLERVFQEEKYLEKIRGKRVALISHSAAINRQGEYSLCVFNKHKGVCKLSALCTLEHGYFGASIAETPGYDPILED
IPVISLFASKEIPAEVIEACDVFVYDVQDIGVRSYSFISALLQVVKASASSKKELIVLDRPNPMGGNLVDGPLPDKEAFPAIPYCYGMTPGELALLYRAR
YAPNASVTVVPMQGWKRSMIEADTGLIWVPTSPQIPDAQSAYFYATTGIIGALSITNIGIGYTLPFKVLGAPWMDGCKVAQELNKARLPGVHFLPFMYEP
FFGKFKMEMCSGVLVVLQDPKQFLPMETQSVILGVLKTLYPKEVEQAFLLLDRLVPRRKAIQNLLGHSEFLNVCLHKKYITWPLRTLCAEGRKQFIEQRQ
PFLLPEYAR
SEQ ID 172:
ATGAAAACAATCTGTAAGCTAGTGATCCTTGCGCTACTATTTCCTAATGTGAGCTATGCTCTTGTACAGGTAGGCTTGGAACGCGTGTTTCAAGAAGAAA
AATATCTTGAGAAAATACGTGGCAAGCGGGTTGCATTGATTTCTCATAGTGCAGCCATTAATCGACAAGGGGAACATTCGCTTTGTGTTTTTAACAAGCA
TAAAGGGGTTTGTAAGCTCAGTGCTTTATGCACACTAGAACATGGGTATTTTGGGGCATCCATTGCTGAGACACCAGGATATGATCCTATCTTAGAAGAT
ATCCCAGTCATTTCTCTATTTGCTTCTAAAGAGATTCCTGCTGAAGTCATTGAGGCCTGCGATGTTTTTGTGTACGATGTACAAGATATTGGTGTGCGGT
CCTATTCATTCATTTCTGCATTGTTGCAAGTCGTAAAAGCATCTGCGAGCAGCAAGAAGGAATTAATTGTTCTGGATCGTCCCAATCCTATGGGAGGGAA
TCTTGTCGATGGCCCTCTCCCTGATAAAGAGGCTTTCCCTGCGATTCCCTATTGCTATGGGATGACACCAGGTGAACTAGCTTTATTGTATCGAGCTCGA
TATGCACCCAATGCCTCGGTGACAGTTGTCCCTATGCAAGGGTGGAAGCGCTCCATGATTTTTGCTGATACAGGATTGATTTGGGTTCCTACAAGTCCTC
AGATTCCAGATGCGCAGTCTGCATATTTTTACGCTACAACAGGTATTATAGGAGCTTTATCTATCACAAACATAGGGATAGGCTATACGCTTCCCTTTAA
AGTTTTAGGGGCTCCCTGGATGGATGGGTGTAAGGTCGCTCAGGAGTTAAATAAAGCGCGGCTACCAGGCGTCCATTTTCTTCCTTTTATGTATGAGCCG
TTTTTTGGGAAATTTAAAATGGAAATGTGTTCTGGAGTTTTGGTCGTACTTCAAGATCCTAAACAATTTCTTCCTATGGAAACACAAAGTGTGATTTTGG
GAGTTTTGAAAACTTTATACCCTAAAGAGGTAGAGCAAGCCTTCTTATTATTAGATCGGTTAGTGCCTCGACGTAAGGCAATTCAAAATTTATTAGGGCA
TTCGGAATTTTTGAATGTCTGTTTACACAAAAAGTATATCACATGGCCGTTACGAACTCTGTGTGCGGAAGGTAGAAAACAATTTATAGAACAGCGACAA
CCCTTCCTTCTCCCAGAATATGCTCGATAG
SEQ ID 173:
MRKTIFKAFNLLFSLLFLSSCSYPCRDWECHGCDSARPRKSSFGFVPFYSDEEIQQAFVEDFDSKEEQLYKTSAQSTSFRNITFATDSYSIKGEDNLTIL
ASLVRHLHKSPKATLYIEGHTDERGAAAYNLALGARRANAVKQYLIKQGIAADRLFTISYGKEHPVHPGHNELAWQQNRRTEFKIHAR
SEQ ID 174:
ATGAGAAAGACTATTTTTAAAGCGTTTAATTTATTATTCTCCCTTCTTTTTCTTTCTTCATGCTCTTATCCTTGCAGAGATTGGGAATGCCATGGTTGCG
ACTCCGCAAGACCTCGTAAATCCTCTTTTGGATTCGTACCTTTCTACTCCGATGAAGAAATTCAACAAGCTTTTGTTGAAGATTTTGATTCCAAAGAAGA
GCAGCTGTACAAAACGAGCGCACAGAGTACCTCTTTCCGAAATATCACTTTCGCTACAGATAGTTATTCTATTAAAGGAGAGGATAACCTCACGATTCTT
GCAAGCTTAGTTCGTCATTTGCATAAATCTCCTAAAGCTACGCTATATATAGAGGGCCATACAGATGAACGTGGAGCTGCAGCTTATAACCTAGCTTTAG
GAGCTCGTCGTGCGAATGCTGTAAAACAATACCTCATCAAACAGGGAATCGCTGCAGACCGCTTATTCACTATTTCTTACGGAAAAGAACATCCTGTTCA
TCCAGGCCATAATGAATTAGCTTGGCAACAAAATCGTCGTACTGAATTTAAGATCCATGCTCGCTAA
SEQ ID 175:
MKGSVVFLRSLLCLLCLLPSTLHCEDLEIHVRSESSLLPIAVSLLSSPKDSRQASYLASLRDLFARDLALGDLLAPTKELAPQTIFIEASYPELIFSLKK
EGKGSQKIFSLELSGDPSKDHQAIHEAADRIHFLLTRVPGISSGKIIFSLCATNSSTELKQGELWSVDYDGQHLYPLTNEHSLSVTPTWMHISHIPAYMY
VSYKLGVPKIFLNTLNQPAGKKILAMQGNQFMPTFSPKTKLLAFISDRDGNPDLFVQSFSLATGAIGTPKKLLNEAFGTQGNPSFSPDGTRLVFVSNKDG
TPRIYQMQISPEQHSPRLLTKKYRNSSCPTWSPDGKKIAFCSVIKGVRQICVYDLASGRDEQLTTSTEHKESPSWAADSNHLVYSAGSSNTSELFLLSLI
TKKSRKIVIGSGEKRFPCWGAFPSQHIKKTS
SEQ ID 176:
ATGAAAGGCTCCGTTGTGTTTCTCCGTTCTCTTCTCTGTCTACTTTGTCTTCTCCCTTCCACTCTCCACTGTGAAGATTTGGAAATTCATGTACGATCAG
AAAGCTCTCTCCTTCCAATCGCAGTCTCTTTGCTCTCATCACCAAAAGACTCTCGTCAAGCTTCCTATCTTGCATCCCTCCGAGACTTATTTGCTCGCGA
TTTGGCTTTAGGAGACCTGTTGGCGCCTACAAAAGAGCTGGCTCCGCAAACGATCTTTATAGAAGCGTCCTATCCAGAACTGATTTTTTCTTTAAAAAAA
GAGGGTAAAGGATCTCAAAAAATTTTCTCTCTAGAGCTCTCTGGAGATCCTTCTAAAGATCATCAAGCGATTCATGAGGCTGCAGATCGCATCCATTTTC
TTCTTACACGCGTTCCTGGAATTAGCTCAGGAAAAATTATTTTTTCCCTATGTGCTACAAACTCTTCCACAGAATTAAAACAAGGGGAACTCTGGTCCGT
TGATTACGATGGACAACATCTTTACCCACTTACCAATGAACATTCCTTATCTGTAACTCCAACCTGGATGCATATCAGTCACATTCCCGCTTATATGTAT
GTTTCCTACAAATTAGGGGTCCCAAAAATCTTTCTGAATACTCTGAACCAGCCTGCAGGGAAAAAAATCCTTGCTATGCAAGGGAATCAGTTTATGCCGA
CTTTCTCTCCTAAAACTAAACTCCTCGCCTTTATTTCTGATAGAGACGGCAATCCTGATCTTTTTGTACAATCATTCTCACTAGCTACCGGAGCAATTGG
CACACCAAAAAAACTCCTAAATGAAGCTTTTGGAACACAAGGAAACCCTTCCTTTAGCCCTGACGGCACCCGTTTAGTTTTTGTTTCTAACAAAGACGGA
ACGCCTCGTATTTATCAGATGCAAATCTCTCCCGAACAACATTCTCCTCGCTTACTAACAAAAAAATATCGAAATAGCAGTTGCCCAACATGGTCTCCAG
ATGGTAAAAAAATAGCCTTCTGCTCAGTCATTAAAGGTGTCCGTCAGATTTGTGTGTATGATCTGGCTTCAGGAAGAGATGAGCAATTAACTACATCTAC
TGAACATAAAGAAAGCCCTTCTTGGGCTGCGGATAGTAACCACCTTGTTTATAGTGCCGGATCTTCCAATACATCCGAACTATTCCTGCTGAGCCTAATT
ACCAAAAAAAGTAGGAAAATTGTTATAGGATCAGGAGAGAAACGTTTCCCATGCTGGGGAGCATTTCCTTCACAACATATAAAGAAAACCTCATGA
SEQ ID 177:
MPKFQYAPFLCTSIIIHIALGGMLFFSAPQKKKPRLSPFKERIVALPPEPKITTTLQTPSPQPIRKPVKNAPAPEKKAAKPPAISNPQKSPQKPNKASPT
PRNETLEKKQATLKKLAQLANQLAEEAETQESYIAQFSWPAQAQVLTENTSYQQDAFCALFQQYVSLPFPGEVRLKLEFSSEGALLHCSILSTISHADKQ
HILNQIQKIPFQSFFSAYKTSKNIVFHIRLQGNSA
SEQ ID 178:
ATGCCAAAATTTCAATATGCCCCTTTTCTTTGCACTTCTATAATCATCCATATTGCTCTTGGAGGAATGCTCTTTTTCTCCGCGCCTCAAAAAAAGAAGC
CTCGTCTCTCCCCTTTTAAAGAACGTATCGTCGCCCTACCCCCTGAACCTAAAATCACTACCACTTTACAGACTCCCTCTCCACAACCTATTCGTAAACC
GGTAAAAAACGCTCCAGCTCCCGAGAAAAAAGCTGCAAAACCTCCCGCGATCTCTAACCCTCAAAAATCTCCTCAAAAACCAAACAAAGCGAGTCCTACG
CCGCGTAATGAGACACTAGAGAAAAAACAAGCTACTCTCAAAAAATTAGCTCAACTAGCTAATCAGCTGGCCGAAGAGGCTGAGACACAAGAATCCTACA
TCGCACAATTTTCTTGGCCTGCTCAAGCGCAAGTTCTTACTGAAAACACATCCTATCAGCAAGATGCCTTCTGTGCTTTATTTCAGCAGTACGTGAGTCT
TCCTTTCCCTGGAGAGGTTCGCCTAAAACTAGAATTTTCTAGTGAAGGCGCTCTTCTCCATTGCTCAATCTTATCTACTATTAGCCATGCTGATAAACAA
CATATCCTGAACCAAATTCAGAAAATTCCTTTTCAATCTTTCTTTAGCGCATACAAAACCTCGAAAAATATCGTTTTTCATATTAGACTGCAGGGAAATT
CTGCTTGA
SEQ ID 179:
MKRFVYEDLEEDPSVSLTPLIDIVFVILMAFMIAMPLIKIDRISLATGSSSHQAFKKQESQQAEIKVFRNHTITLNDLPMSLQELRSQLTVIHAQHPNIV
PLLLQDGDTAFKLYQEIKSTIEEAGFQELHIALKN
SEQ ID 180:
ATGAAACGCTTCGTTTACGAAGATCTAGAAGAAGACCCTAGTGTCAGTCTTACTCCTCTGATCGATATCGTCTTTGTAATTTTGATGGCGTTCATGATCG
CCATGCCTCTTATTAAAATTGATCGTATCTCTTTAGCCACAGGATCTTCCTCACACCAAGCCTTTAAAAAACAAGAGTCTCAGCAAGCTGAAATTAAAGT
GTTTCGAAACCATACCATTACTCTCAATGACCTTCCTATGTCTCTCCAAGAGTTACGCTCGCAACTAACAGTCATCCATGCGCAACACCCTAATATAGTT
CCGCTGCTCTTACAAGACGGTGATACAGCTTTCAAACTGTATCAAGAGATCAAATCGACTATCGAAGAAGCCGGATTTCAGGAACTTCATATTGCTTTGA
AGAACTAA
SEQ ID 181:
MFQLANNPIIQSFQEADLFGKVIFFSLFALSICTWTVLHQKLSIQKKFLKSGKSLKEFLIKNRHSPLSLDIHPESTPFTDLYFTIKRGTLELLDKNRQLA
PERTPLLSVEDIQSLETLFNAVMPKYRALLNKNNFIPATTISIAPFLGLLGTVWGILLAFAHISTGQANGTIMMEGLATALGTTIVGLFVAIPSLVGFNY
LRAHAFQVSLEIEQTAFLLLNSIEVKYRQTSL
SEQ ID 182:
ATGTTCCAACTCGCAAATAATCCCATCATTCAGTCCTTTCAAGAAGCCGATCTTTTTGGAAAGGTCATTTTCTTTTCGCTGTTCGCTCTTTCGATATGTA
CATGGACAGTCCTTCATCAGAAACTCTCCATTCAAAAGAAATTTCTAAAATCAGGGAAATCTTTAAAAGAGTTTTTAATAAAAAATCGTCATTCTCCTCT
CTCCTTAGATATTCATCCTGAATCCACGCCTTTTACAGACCTCTATTTTACTATCAAACGTGGAACCCTGGAATTACTAGATAAGAATAGACAGTTGGCT
CCAGAACGAACTCCTTTGCTTTCCGTGGAAGATATTCAATCGTTGGAAACGCTTTTTAATGCAGTGATGCCGAAATATAGAGCTCTCTTAAATAAAAATA
ACTTCATTCCAGCAACGACCATTAGTCTCGCTCCTTTTCTAGGACTATTAGGGACCGTTTGGGGGATTCTATTAGCTTTTGCGCACATTAGTACCGGACA
AGCCAATGGGACGATCATGATGGAAGGCTTAGCAACAGCATTAGGAACAACTATTGTAGGGCTATTTGTTGCCATCCCCTCACTAGTAGGTTTCAATTAT
CTACGCGCCCACGCCTTCCAAGTCTCTCTGGAAATCGAGCAAACTGCTTTTCTTTTACTTAACTCTATTGAAGTCAAATATCGACAAACTAGCTTATGA
SEQ ID 183:
MSRLDVSVFDSLANKEKASLLEEVLCGENLQDFTTYSKVALAKKNLAIARKLASYILNEEGDLELSRVVESIQLLTKCLYPLGPYRQEEGPIREHVLKML
EFLRDDQEIKNRFRRFFVPSYARVQDLIRNTLALPASETVTVRHVREAALVALFTYLRQDVGSCFATALAILIHREYPLLFIRDLEDLLSSGKISRIVGD
REISVPINLLPCVGDLFKPICVMDLYPNPVATLAASSDLQAAFVASGIFPTTGDIAGEVQTLLANEFIYQKVQDIHGKITAHDVIQDSLLHHYQLSLSTV
QASVLQEGFRKERGDGTVLLSTNSQRVLSYLESHEQAKLGFIRDTQNVLLKSWEYTLATLADASQTTTTKHLQIALGWTSDDEDGLREIIRRFLAEEVAT
TQAFAGQCEETYQEAKAQLEHVESRMRNPINKQDSQILAMDHVRFRQELNQALQDWNAAQEKLKKMIMLPDFLLSFYSREIPNYFRSVYDAFIREFSGNY
QDVPAGFRILFTYGRSHPNTWEPIYSIEEFIHALTEFFTSIEGDLLAKHNVSGLEKETSILLHRIVSALHEPRFQEAAMERILKAYNCPIPQGIFQHLDQ
VTHTPWVYVSGGTVTTLVGDYFENSKPLVKLEKLPADPHELAAFFADALKDLPEAVKDYVENGDHSLLAAAPSHVFSVMAGAPLFRDAWTNDWYSYTWLR
DVWLSKHQDFLKRTLFDKSAIYAFITRFCTRYYLQELTQDFLYFCDDLSLSIPEFYEKSSRFFQSTVHDEKVVATLQKYLASQFVHEAPYVSEQQLPQII
SDLSSYLGISSRISYDRFATLLEENVGKHSLLSSSDLRHLYKGLLMAGYQRVYHEEDLSMRLIAAMRHYGLAYPAPLLFGDTNWAYRYFGFILHPGTQEM
DLWEFNYLGLVGRPSENKERWFVVRDPWALYPNPIDYGMAPPPGYRSGLPKGFF
SEQ ID 184:
ATGTCTCGTTTGGACGTTTCTGTATTTGATTCCTTAGCTAATAAAGAAAAAGCTTCCTTACTGGAGGAGGTTTTGTGTGGTGAGAACCTGCAAGATTTCA
CAACGTATAGCAAAGTTGCTTTAGCAAAAAAAAATCTTGCTATTGCAAGGAAGTTAGCCAGTTATATCCTGAATGAAGAAGGAGATTTGGAGCTTAGTCG
AGTTGTTGAAAGTATTCAGCTGTTGACGAAATGTTTATATCCCTTAGGACCGTATCGCCAGGAAGAAGGGCCGATTCGTGAGCATGTATTAAAGATGCTG
GAGTTTTTACGGGATGATCAAGAAATTAAAAATCGTTTTCGAAGGTTTTTTGTACCTTCTTACGCTAGAGTTCAAGATTTAATTCGGAATACGTTAGCGT
TGCCCGCTAGTGAGACAGTAACCGTACGGCATGTACGTGAAGCCGCTTTAGTCGCATTATTTACCTATTTGCGACAAGATGTCGGATCTTGTTTCGCAAC
AGCATTAGCAATTCTTATCCATCGGGAGTATCCATTATTATTTATTCGTGATTTGGAAGATTTATTATCTTCCGGGAAAATATCCCGTATCGTTGGTGAT
CGAGAGATTTCCGTTCCGATCAATCTTCTACCGTGTGTAGGAGATTTATTTAAGCCTATTTGTGTAATGGATTTATATCCCAATCCTGTGGCTACTCTTG
CTGCTTCGTCAGATTTACAAGCAGCATTCGTAGCTTCTGGCATATTTCCAACAACAGGGGATATCGCAGGTGAGGTGCAAACGCTACTAGCTAATGAGTT
TATCTATCAAAAAGTTCAGGATATTCATGGGAAGATAACAGCTCATGATGTCATTCAGGATAGTTTGTTACATCACTATCAGCTTTCTCTTTCTACAGTG
CAAGCTTCCGTTTTGCAGGAAGGTTTCCGTAAAGAGCGAGGGGATGGTACGGTTTTGTTGTCTACGAATAGTCAACGTGTACTTAGCTATTTAGAATCTC
ACGAGCAAGCAAAACTGGGATTTATTCGTGATACACAGAATGTATTATTGAAATCGTGGGAATATACGTTAGCAACGTTAGCAGATGCGAGTCAAACAAC
AACCACCAAGCATTTACAAATTGCTTTAGGTTGGACCAGTGATGATGAGGATGGTTTACGTGAAATTATACGTAGATTTTTAGCAGAAGAAGTAGCTACG
ACACAAGCCTTTGCAGGACAATGTGAAGAGACGTATCAAGAAGCAAAAGCGCAGTTAGAACATGTGGAAAGTCGGATGCGTAATCCGATCAATAAACAAG
ATAGCCAAATTCTGGCTATGGATCATGTGCGTTTTCGACAAGAATTGAATCAAGCTTTACAAGATTGGAATGCTGCGCAAGAGAAGCTGAAAAAAATGAT
CATGCTACCAGACTTTCTCTTGTCTTTTTATTCACGAGAAATCCCTAACTATTTCCGTAGCGTATACGATGCTTTTATTAGAGAGTTTTCTGGGAATTAT
CAAGATGTTCCTGCGGGCTTTCGTATATTATTTACCTATGGGAGGAGTCATCCTAACACGTGGGAGCCGATTTATTCTATCGAAGAATTTATTCATGCTT
TGACGGAGTTTTTTACTTCTATAGAAGGAGATCTCCTAGCGAAGCATAATGTTTCTGGATTAGAAAAAGAAACTTCTATTCTTTTGCATCGTATTGTATC
GGCTTTACATGAACCTCGTTTTCAGGAGGCTGCAATGGAAAGGATCTTGAAAGCTTATAATTGTCCTATTCCACAGGGGATTTTCCAGCATTTAGATCAA
GTTACGCATACCCCTTGGGTTTATGTTTCTGGAGGAACAGTAACGACTTTAGTAGGCGATTATTTTGAAAATTCGAAACCACTCGTCAAACTAGAAAAAT
TGCCTGCGGATCCGCATGAGTTGGCAGCATTTTTTGCTGATGCATTGAAAGATCTTCCTGAGGCTGTGAAAGATTATGTAGAAAATGGGGATCATTCTTT
ATTAGCAGCAGCCCCTTCGCATGTGTTTTCTGTTATGGCAGGAGCTCCGTTATTTAGAGATGCATGGACTAATGATTGGTATAGCTATACTTGGCTGAGA
GATGTGTGGCTTTCTAAGCATCAGGATTTTTTGAAGCGTACTCTTTTCGATAAATCGGCAATATATGCGTTTATTACACGTTTCTGTACACGGTATTATC
TCCAAGAACTTACCCAAGATTTCTTATATTTTTGTGATGATCTCTCGTTATCTATTCCTGAATTCTATGAAAAGAGCTCGCGTTTCTTTCAGTCGACTGT
TCATGATGAGAAAGTAGTAGCTACTTTACAGAAATATTTAGCGAGCCAGTTCGTACATGAAGCGCCTTATGTTTCTGAACAGCAGTTACCCCAGATTATC
AGTGATCTTTCTTCTTATTTAGGGATTTCTTCTCGGATATCCTATGATCGATTCGCTACCCTACTAGAAGAGAATGTAGGGAAGCATTCGCTATTATCTT
CCTCGGATCTCAGACATCTGTATAAAGGTTTATTAATGGCTGGGTATCAGCGTGTTTATCATGAAGAAGATCTTTCTATGAGGCTGATTGCTGCTATGCG
TCACTATGGGTTAGCCTATCCTGCTCCGCTTCTTTTTGGTGATACGAATTGGGCTTACCGGTATTTTGGTTTTATTTTGCATCCTGGAACCCAAGAGATG
GATTTGTGGGAATTTAATTATTTAGGATTGGTAGGACGTCCTTCAGAAAATAAAGAACGATGGTTTGTTGTTCGAGATCCTTGGGCGTTGTATCCGAATC
CCATAGATTACGGAATGGCCCCTCCACCAGGCTATCGAAGTGGATTGCCGAAAGGCTTTTTTTAG
SEQ ID 185:
MRLTFTKRILLFLFLVIPAPLLLNLVVLSFFSFVAVKTTIIQDLHTRTMNFNLELEKKIAIQNIFLKRLAETLALKTLTTSHDFFTEAYSEMIALGDTDL
SLCLLSSANDSIRTKNPRDPFVRYIKAHPEIRDKLIQNPGNASLISISERPDTEDHYLIFAEPLPIYEDPSLAGWVIAFYSMQKLRNYLFHNKQSYQDLL
CYLNHKGELLFSNSSPFQNGAFSLSMEGYPALSSEKASYPLEPSPELFKAKELLKVSIHGKTFLAYLSPWQPIPHTHSLALIPLSTCITQALRLPINVIL
FYILAFSLMGWVLSCTSKRLNRPLQELSVSMESAWKGNHNVRYEPQPYGYEINELGNIFNCTLLLLLNVKEKAEIEYISGNLLQKELALLSSLKDTLLCQ
RSNSLPGGTFSLHYLQGEQQTGYFYGWVATPEKDRLFGVIGIAGDIGLPSYLYALSARSLFLTYASLGYSLPSICHKTMRSFDETTVGNEASISIACLEY
DLSSKSLSVLTEGANPPTLFIKRQEHLLTMSEQQRIETGDILVCLTGGPHIIQYLKTLPIEALLKDPLAPLNSENFAEMLTTMLRNKNQTQIDGAVGFLS
FI
SEQ ID 186:
ATGAGACTGACATTCACCAAAAGAATCCTTCTTTTTCTTTTCCTAGTGATTCCTGCTCCTCTCCTTCTCAATCTCGTTGTCCTTTCTTTCTTTTCCTTCG
TGGCTGTTAAAACAACGATCATTCAGGATCTGCATACCCGCACCATGAACTTTAATTTAGAACTCGAAAAGAAAATCGCTATTCAAAATATTTTTCTGAA
ACGTTTAGCGGAAACGTTAGCATTAAAAACCCTCACAACCTCACATGATTTTTTCACTGAAGCTTATAGTGAGATGATTGCTCTCGGAGATACCGATTTA
TCCCTCTGCCTACTTTCTTCCGCTAACGATAGCATCCGTACAAAGAATCCTCGGGATCCTTTTGTTCGTTATATAAAAGCTCATCCAGAAATACGTGATA
AGCTTATCCAAAATCCTGGGAATGCTAGCCTTATCTCTATTTCTGAACGCCCAGACACCGAAGATCATTACCTTATTTTTGCAGAACCACTTCCTATCTA
CGAAGACCCCTCATTAGCCGGCTGGGTAATTGCTTTCTATTCGATGCAAAAACTACGCAACTATCTCTTCCATAACAAACAATCCTATCAAGATCTTCTT
TGCTATCTCAACCATAAGGGAGAACTTCTCTTTTCAAACTCATCTCCTTTTCAAAATGGAGCTTTTTCTCTCTCCATGGAAGGATATCCCGCTCTCTCTT
CAGAAAAAGCTTCTTATCCTTTAGAACCTTCTCCTGAATTATTTAAAGCTAAAGAGCTGTTAAAAGTTTCCATACACGGGAAAACTTTCTTAGCCTATTT
ATCTCCTTGGCAGCCTATACCACATACCCATTCTCTTGCGCTGATCCCTCTATCCACTTGCATTACACAAGCCTTACGGCTTCCCATCAACGTAATCTTA
TTCTATATCCTCGCTTTTTCTTTGATGGGATGGGTGCTCTCTTGCACTAGCAAACGATTAAATCGTCCCTTACAAGAGCTTTCTGTCAGTATGGAATCCG
CGTGGAAAGGCAACCATAATGTCCGCTATGAGCCGCAACCTTATGGCTATGAAATCAATGAACTGGGGAATATTTTTAACTGTACTTTACTTCTTCTGCT
GAACGTCAAAGAAAAAGCTGAAATAGAATATATTTCCGGAAATTTATTACAAAAAGAGCTTGCTCTTCTCTCTTCCTTAAAAGATACCCTTCTCTGTCAA
CGTTCGAATTCTCTCCCAGGAGGAACTTTCTCTTTGCATTATTTACAAGGAGAACAACAAACCGGATATTTTTATGGTTGGGTTGCCACTCCTGAAAAAG
ATCGCCTCTTCGGAGTGATTGGAATAGCTGGAGATATCGGACTGCCTTCTTATCTCTACGCACTCTCTGCCCGCAGTTTATTCCTAACGTATGCAAGTTT
AGGCTACTCATTACCTTCTATTTGCCATAAAACGATGCGAAGCTTTGATGAAACAACTGTAGGCAATGAAGCTTCTATTTCTATAGCTTGTCTTGAATAC
GACCTTTCTTCCAAGTCATTGTCTGTTCTAACAGAAGGTGCTAATCCTCCAACTCTATTCATAAAACGACAAGAACATCTCCTCACGATGTCAGAACAAC
AACGTATTGAGACCGGAGATATCCTTGTTTGCCTTACTGGAGGGCCCCACATCATTCAGTACTTGAAAACACTCCCTATAGAAGCATTACTAAAAGATCC
TCTCGCTCCACTCAATTCTGAAAACTTTGCAGAGATGTTAACAACGATGCTGAGAAATAAAAATCAAACGCAGATCGATGGAGCTGTAGGCTTTTTATCC
TTTATCTAA
SEQ ID 187:
MQAAHHHYHRYTDKLHRQNHKKDLISPKPTEQEACNTSSLSKELIPLSEQRGLLSPICDFISERPCLHGVSVRNLKQALKNSAGTQIALDWSILPQWFNP
RVSHAPKLSIRDFGYSAHQTVTEATPPCWQNCFNPSAAVTIYDSSYGKGVFQISYTLVRYWRENAATAGDAMMLAGSINDYPSRQNIFSQFTFSQNFPNE
RVSLTIGQYSLYAIDGTLYNNDQQLGFISYALSQNPTATYSSGSLGAYLQVAPTASTSLQIGFQDAYNISGSSIKWSNLTKNRYNFHGFASWAPRCCLGS
GQYSVLLYVTRQVPEQMEQTMGWSVNASQHISSKLYVFGRYSGVTGHVFPINRTYSFGMASANLFNRNPQDLFGIACAFNNVHLSASPNTKRKYETVIEG
FATIGCGPYLSFAPDFQLYLYPALRPNKQSARVYSVRANLAI
SEQ ID 188:
ATGCAGGCTGCACACCATCACTATCACCGCTACACAGATAAACTGCACAGACAAAACCATAAAAAAGATCTCATCTCTCCCAAACCTACCGAACAAGAGG
CGTGCAATACTTCTTCCCTTAGTAAGGAATTAATCCCTCTATCAGAACAAAGAGGCCTTTTATCCCCCATCTGTGACTTTATTTCGGAACGCCCTTGCTT
ACACGGAGTTTCTGTTAGAAATCTCAAGCAAGCGCTAAAAAATTCTGCAGGAACCCAAATTGCACTGGATTGGTCTATTCTCCCTCAATGGTTCAATCCT
CGGGTCTCTCATGCCCCTAAGCTTTCTATCCGAGACTTTGGGTATAGCGCACACCAAACTGTTACCGAAGCCACTCCTCCTTGCTGGCAAAACTGCTTTA
ATCCATCTGCGGCCGTTACTATCTATGATTCCTCATATGGGAAAGGGGTCTTTCAAATATCCTATACCCTTGTCCGCTATTGGAGAGAGAATGCTGCGAC
TGCTGGCGATGCTATGATGCTCGCAGGGAGTATCAATGATTATCCCTCTCGTCAGAACATTTTCTCTCAGTTTACTTTCTCCCAAAACTTCCCAAATGAA
CGGGTGAGTCTGACAATTGGTCAGTACTCACTCTATGCAATAGACGGAACATTATACAATAACGATCAACAACTTGGATTCATTAGTTACGCATTATCAC
AAAATCCAACAGCAACTTATTCCTCTGGAAGTCTTGGAGCTTACCTACAAGTCGCTCCTACCGCAAGCACAAGTCTTCAAATAGGATTTCAAGACGCTTA
TAATATCTCCGGATCCTCTATCAAATGGAGTAACCTTACAAAAAATAGATACAATTTTCACGGTTTTGCTTCCTGGGCTCCCCGCTGTTGCTTAGGATCT
GGCCAGTACTCCGTGCTTCTTTATGTGACTAGACAAGTTCCAGAACAGATGGAACAAACAATGGGATGGTCAGTCAATGCGAGTCAACACATATCTTCTA
AACTGTATGTGTTTGGAAGATACAGCGGTGTTACAGGACATGTGTTCCCGATTAACCGCACGTATTCATTCGGTATGGCCTCTGCAAATTTATTTAACCG
TAACCCACAAGATTTATTTGGAATTGCTTGCGCATTCAATAATGTACACCTCTCTGCTTCTCCAAATACTAAAAGAAAATACGAAACTGTAATCGAAGGG
TTTGCAACTATCGGTTGCGGCCCCTATCTTTCTTTCGCTCCAGACTTCCAACTCTACCTCTACCCAGCTCTTCGTCCAAACAAACAATCTGCCCGTGTTT
ATAGCGTGCGAGCTAATTTAGCTATCTAA
SEQ ID 189:
MFDVVISDIEAREILDSRGYPTLCVKVITNTGTFGEACVPSGASTGIKEALELRDKDPKRYQGKGVLQAISNVEKVLMPALQGFSVFDQITADAIMIDAD
GTPNKEKLGANAILGVSLALAKAAANTLQRPLYRYLGGSFSHVLPCPMMNLINGGMHATNGLQFQEFMIRPISAPSLTEAVRMGAEVFNALKKILQNRQL
ATGVGDEGGFAPNLASNAEALDLLLTAIETAGFTPREDISLALDCAASSFYNTQDKTYDGKSYADQVGILAELCEHYPIDSIEDGLAEEDFEGWKLLSET
LGDRVQLVGDDLFVTNSALIAEGIAQGLANAVLIKPNQIGTLTETAEAIRLATIQGYATILSHRSGETEDTTIADLAVAFNTGQIKTGSLSRSERIAKYN
RLMAIEEEMGPEALFQDSNPFSKA
SEQ ID 190:
ATGTTTGATGTCGTCATCTCCGATATAGAAGCGAGAGAAATTTTAGATTCTCGAGGCTATCCCACATTATGTGTTAAAGTCATCACTAATACAGGAACCT
TTGGTGAAGCGTGCGTTCCTTCTGGAGCATCTACAGGCATCAAGGAAGCTTTGGAACTGCGTGACAAAGATCCTAAACGTTACCAAGGGAAAGGGGTCTT
ACAAGCCATTTCTAATGTCGAAAAAGTGCTGATGCCCGCTTTACAAGGATTCAGCGTATTTGACCAAATTACAGCTGATGCGATTATGATTGATGCTGAT
GGAACTCCGAACAAAGAAAAGTTAGGAGCTAATGCGATTCTTGGAGTCTCCCTAGCATTAGCAAAAGCTGCTGCAAATACTTTACAGAGACCTTTATATC
GGTATCTTGGTGGATCTTTCTCGCATGTGCTTCCTTGCCCTATGATGAATCTTATCAATGGCGGTATGCATGCTACAAATGGTCTCCAATTCCAAGAATT
TATGATTCGTCCAATTAGCGCTCCTTCTCTAACAGAGGCTGTGCGGATGGGAGCAGAAGTCTTCAACGCCTTAAAAAAAATCTTACAGAATCGACAGCTG
GCTACAGGTGTTGGTGATGAAGGCGGATTTGCTCCTAATCTTGCCTCTAATGCCGAAGCTCTGGATCTACTCTTAACAGCAATCGAAACTGCAGGATTCA
CACCTAGAGAAGATATTTCTTTAGCTCTCGACTGCGCTGCTTCTTCTTTCTATAATACCCAAGATAAAACCTATGATGGGAAATCGTATGCAGATCAAGT
GGGTATACTTGCAGAACTCTGTGAGCACTATCCTATAGATTCTATCGAAGATGGGCTAGCCGAAGAAGATTTTGAGGGCTGGAAACTCCTATCCGAGACT
TTAGGAGATCGTGTGCAACTAGTTGGAGACGACCTATTTGTGACGAATTCTGCATTGATTGCTGAAGGAATCGCTCAAGGACTTGCCAATGCCGTTCTCA
TCAAACCAAACCAAATTGGAACACTTACAGAAACTGCAGAAGCTATTCGTTTAGCAACTATACAAGGCTACGCTACCATTCTTTCGCATAGATCAGGAGA
AACAGAAGATACTACCATAGCAGACCTTGCTGTCGCTTTTAATACAGGTCAGATTAAAACAGGGTCTCTTTCCCGTTCTGAGCGTATCGCTAAGTATAAC
CGTCTAATGGCAATTGAAGAAGAGATGGGTCCAGAAGCTCTATTCCAAGATTCAAATCCCTTTTCTAAAGCATAG
SEQ ID 191:
MKNILGYGFLGTFCLGSLTVPSFSITITEKLASLEGKTESLAPFSHISSFNAELKEANDVLKSLYEEALSLRSRGETSQAVWDELRSRLIGAKQRLRSLE
DLWSVEVAERGGDPEDYALWNHPETTIYNLVSDYGDEQSIYVIPQNVGAMRITAMSKLVVPKEGFEECLSLLLMRLGIGIRQVSPWIKELYLTNREESGV
LGIFGSRQELDSLPMTAHIAFVLSSKNLDARADVQALRKFANSDTMLIDFIGGKVWLFGAVSEITELLKIYEFLQSDNIRQEHRIVSLSKIEPLEMLAIL
KAAFREDLAKEGEDSSGVGLKVVPLQNHGRSLFLSGALPIVQKAIDLIRELEEGIESPTDKTVFWYHVKHSDPQELAALLSQVHDIFSNGAFGASSSCDT
GVVSSKAGSSSNGLAVHIDTSLGSSVKEGSAKYGSFIADSKTGTLIMVIEKEALPKIKMLLKKLDVPKKMVRIEVLLFERKLSNQRKSGLNLLRLGEEVC
KQGTQAVSWASGGILEFLFKGGAKGIVPSYDFAYQFLMAQEDVRINASPSVVTMNQTPARIAIVEEMSIVVSSDKDKAQYNRAQYGIMIKILPVINIGEE
DGKSFITLETDITFDSTGRNHADRPDVTRRNITNKVRIQDGETVIIGGLRCNQTMDSRDGIPFLGELPGIGKLFGMDSASDSQTEMFMFITPKILDNPSE
TEEKLECAFLAARPGENDDFLRALVAGQQAAKQAIERKESTVWGEESSGSRGRVEYDGRE
SEQ ID 192:
GTGAAAAATATTTTGGGCTATGGGTTTCTAGGGACTTTTTGTTTGGGAAGTTTGACGGTTCCTAGTTTTTCCATCACGATTACAGAAAAATTGGCTTCTC
TAGAAGGAAAAACGGAATCGCTAGCCCCTTTTTCGCATATTTCATCTTTTAATGCTGAATTGAAAGAGGCAAATGATGTTCTCAAATCTTTATACGAAGA
AGCTTTGTCTCTCCGTTCTCGAGGAGAGACTTCGCAGGCGGTATGGGACGAGTTGCGAAGCCGATTGATCGGCGCTAAACAACGGATACGTTCATTGGAA
GATTTATGGTCAGTAGAGGTTGCAGAAAGGGGGGGGGATCCCGAAGACTATGCCCTTTGGAATCATCCAGAAACTACGATTTATAATCTGGTCAGTGATT
ACGGAGATGAACAGAGTATCTATGTGATTCCTCAAAATGTTGGGGCGATGCGTATCACAGCCATGTCTAAGCTAGTGGTCCCTAAAGAAGGATTTGAGGA
ATGTTTGTCTTTGCTTTTAATGCGGCTGGGTATTGGGATCAGACAGGTTAGTCCTTGGATTAAGGAGCTGTATTTAACTAATAGGGAAGAGTCTGGTGTT
TTAGGTATCTTTGGATCTAGACAAGAGCTAGATAGCTTGCCTATGACGGCACATATTGCTTTTGTACTTTCTTCTAAAAATTTAGATGCACGAGCGGATG
TACAAGCTTTGCGCAAGTTCGCAAATAGCGATACCATGTTAATTGATTTTATAGGGGGGAAAGTTTGGTTATTTGGAGCTGTCAGCGAGATTACCGAGCT
CCTTAAAATCTATGAATTCTTACAATCAGACAACATTCGACAAGAGCATCGCATTGTTTCTTTATCAAAAATAGAACCCTTAGAAATGCTGGCTATTTTG
AAAGCAGCTTTCCGAGAAGATTTAGCTAAAGAGGGAGAAGATTCTTCTGGAGTGGGATTAAAAGTGGTCCCTTTACAAAACCATGGACGCTCGCTTTTCT
TAAGTGGAGCTCTTCCCATCGTTCAGAAGGCAATAGATCTTATTCGGGAACTAGAAGAGGGGATAGAGAGCCCTACCGACAAAACGGTATTTTGGTATCA
TGTCAAACACTCAGATCCTCAGGAGCTTGCAGCGCTTCTTTCTCAAGTACATGATATTTTCTCAAATGGTGCTTTTGGGGCATCTAGTAGTTGTGATACT
GGCGTAGTCTCAAGTAAAGCGGGATCCTCTTCGAATGGATTAGCGGTACATATAGATACGTCGCTGGGGAGCTCCGTAAAAGAAGGTTCTGCGAAATATG
GGAGTTTTATTGCAGATTCCAAGACCGGAACCTTGATTATGGTTATTGAGAAAGAAGCTTTACCCAAGATCAAGATGTTGTTGAAGAAACTGGATGTGCC
CAAAAAAATGGTACGTATAGAGGTTCTGCTTTTTGAAAGAAAACTATCCAATCAACGTAAATCTGGATTGAACCTATTGCGTTTAGGAGAAGAGGTTTGT
AAGCAGGGAACGCAAGCCGTTTCGTGGGCAAGTGGGGGCATTCTGGAGTTCCTGTTCAAAGGTGGAGCAAAAGGGATTGTTCCTAGTTATGACTTTGCTT
ATCAGTTTCTCATGGCGCAAGAGGATGTCCGTATTAATGCAAGTCCTTCCGTCGTGACTATGAACCAAACCCCGGCGAGAATTGCGATTGTGGAAGAAAT
GTCAATTGTAGTTTCTTCTGATAAGGATAAAGCCCAATACAATCGAGCTCAATACGGGATTATGATTAAGATTCTTCCCGTTATTAATATCGGAGAAGAG
GATGGGAAGAGCTTTATTACTTTAGAGACCGACATCACGTTTGATTCGACTGGGAGAAATCATGCGGATCGTCCCGATGTTACACGCAGAAATATTACGA
ACAAGGTTCGGATTCAAGATGGCGAAACGGTCATTATTGGGGGGCTTCGTTGTAATCAAACTATGGATTCTCGTGACGGGATTCCATTTTTAGGAGAGTT
GCCAGGAATAGGAAAATTATTTGGTATGGATTCTGCTTCGGACTCACAAACAGAGATGTTTATGTTTATCACTCCGAAGATTTTGGATAATCCTAGTGAG
ACAGAAGAAAAATTAGAATGTGCTTTCCTGGCTGCTCGCCCCGGGGAGAACGATGATTTCCTCAGAGCTTTAGTAGCAGGACAGCAGGCTGCTAAACAGG
CTATAGAAAGAAAAGAGTCTACCGTATGGGGAGAAGAATCCTCCGGCTCTCGAGGAAGGGTGGAGTATGATGGACGGGAATAA
SEQ ID 193:
MMVVITLIGIIGGALAFNMRGSLQKGKIFQTEQNCARVYDVLMMEYASGNLSLKEVIANKEAILEDSAWCKEGKKLLKDAWGEDLLVKMNDKGDDIVVFS
KKVRNEQRG
SEQ ID 194:
ATGATGGTTGTCATTACCCTCATTGGTATTATTGGTGGAGCCTTGGCTTTTAATATGCGAGGGAGTTTGCAAAAAGGGAAAATCTTCCAAACAGAGCAAA
ATTGCGCTCGCGTGTATGACGTCCTTATGATGGAATATGCTTCCGGAAATTTGTCTCTAAAAGAGGTCATCGCAAATAAGGAAGCGATTTTAGAAGATTC
TGCGTGGTGCAAGGAAGGAAAGAAACTTCTTAAAGATGCTTGGGGAGAAGATCTTCTTGTTAAAATGAATGACAAGGGTGACGATATTGTTGTGTTCTCT
AAGAAAGTAAGGAATGAACAGCGAGGGTAA
SEQ ID 195:
MFRKIKKKRAFLLSELLIACVLISLLLGSLGYWTRRIWISHKEKEHVYRIFLNESKTYRFLRGTFLSTIAMEAQEELVFSFDRGVYVDPHLAGVVQGTLH
YDPITQEISLIVASEREEARQEKISLWTHVLSMEWKVLRYQGLGEGPDRVYLTLVRKVGALPPRTLSYIFAVGR
SEQ ID 196:
ATGTTTAGAAAGATAAAAAAGAAACGAGCATTTTTACTTTCAGAACTTCTCATCGCTTGCGTGCTTATCAGTTTGCTGCTCGGCTCTTTAGGGTATTGGA
CACGGAGGATATGGATATCTCATAAAGAGAAAGAGCACGTGTATAGAATCTTTCTCAATGAGAGCAAGACGTATCGATTTTTAAGAGGTACCTTTTTATC
CACTATTGCCATGGAAGCTCAGGAAGAGTTAGTTTTTTCTTTCGATCGGGGAGTGTATGTCGATCCTCACTTAGCAGGTGTTGTGCAAGGGACGTTACAC
TATGACCCCATCACTCAGGAAATTTCTCTAATAGTAGCGAGTGAAAGAGAGGAGGCCCGTCAGGAGAAAATTTCCTTATGGACGCATGTTCTTTCTATGG
AATGGAAAGTTCTTAGATATCAAGGTCTAGGAGAGGGACCAGATAGAGTGTACTTAACACTAGTAAGGAAGGTTGGGGCCTTGCCACCAAGAACCCTTTC
CTATATTTTTGCTGTGGGTAGATAG
SEQ ID 197:
MHFIFTLLCLTSLVTVVSLDAAGTRKRISYAKLQEKEEVAFSAQQSAISEVIYRDKTKRLSSQAKRAEPRTQDKERDSVVVRQKRYRLLEIPFSRPPNNS
RFNLYSLLKESPENYGDPSSAYAIFARLLQGLYVQSELIPQGAEYRVIEALLAQKDEIISRAQELGSDCLETVVLPEEEAGWLYKMLKGTKTTRSLLHFL
NYEEKNTNQGRLNLLFTDPVILQAFINDSKAYSELERVRQEVWESARQQELAIKAYGQAAALEIFKTRTDFRTELQDKTQVILHRYDLLSLLNKKVFDYT
LGTAGDYIFVVDPENEGVNRSRCVSRRKTN
SEQ ID 198:
ATGCATTTTATTTTCACACTACTATGTTTAACCTCGTTGGTGACCGTGGTATCTTTGGATGCTGCCGGAACTCGTAAGAGAATTTCCTATGCAAAACTTC
AAGAAAAGGAAGAAGTAGCTTTTTCTGCGCAACAATCTGCTATTTCTGAAGTGATCTACAGAGATAAAACGAAACGATTGTCTTCCCAGGCGAAAAGAGC
AGAGCCTCGTACGCAAGATAAGGAGCGTGATAGTGTCGTTGTTCGGCAGAAGCGCTATCGACTGTTAGAAATCCCTTTTTCTCGGCCGCCAAATAATTCT
AGGTTCAATCTTTATTCTTTGCTGAAAGAGTCTCCGGAGAATTATGGAGATCCTTCTTCAGCATATGCTATTTTTGCTAGGTTGCTACAAGGACTGTATG
TGCAGTCAGAGCTCATTCCTCAAGGTGCGGAGTATCGTGTTATAGAGGCTTTGCTTGCTCAAAAGGATGAGATTATTTCTCGAGCTCAAGAGCTTGGTTC
GGATTGTCTTGAGACGGTAGTCCTCCCTGAAGAGGAAGCCGGTTGGTTGTACAAGATGCTAAAAGGCACTAAGACAACGCGTTCTTTATTGCATTTTCTC
AACTATGAAGAGAAAAATACCAATCAGGGTAGGTTGAATTTATTGTTCACAGATCCCGTTATTCTTCAAGCATTTATCAATGATTCTAAAGCTTATTCTG
AATTAGAACGTGTACGGCAAGAGGTTTGGGAGAGCGCGCGACAGCAGGAGTTGGCTATTAAAGCTTATGGGCAAGCTGCTGCATTAGAAATTTTTAAAAC
TAGAACGGATTTCCGCACAGAGTTGCAAGACAAAACGCAGGTAATTCTCCATCGATATGATCTTCTTTCTTTACTGAATAAGAAGGTTTTTGATTACACA
TTAGGGACTGCTGGGGATTATATTTTTGTGGTAGACCCAGAAAATGAAGGGGTTAACAGAAGTCGTTGCGTTTCAAGAAGAAAAACTAATTAA
SEQ ID 199:
MFRYTLSRSLFFILALFFCSACDSRSMITHGLSGRDANEIVVLLVSKGVAAQKVPQAASSTGGSGEQLWDISVPAAQITEALAILNQAGLPRMKGTSLLD
LFAKQGLVPSEMQEKIRYQEGLSEQMATTIRKMDGIVDASVQISFSPEEEDQRPLTASVYIKHRGVLDNPNSIMVSKIKRLVASAVPGLCPENVSVVSDR
ASYSDITINGPWGLSDEMNYVSVWGIILAKHSLTKFRLVFYFLILLLFILSCGLLWVIWKTHTLISALGGTKGFFDPAPYSQLSFTQNKPAPKETPGAAE
GAEAQTASEQPSKENAEKQEENNEDA
SEQ ID 200:
ATGTTTCGTTATACTCTTTCTCGATCCTTATTTTTCATTTTGGCTCTTTTCTTCTGCTCGGCTTGTGATAGTCGTTCCATGATTACACACGGCTTGTCAG
GACGTGATGCTAATGAAATCGTAGTGCTTCTAGTCAGTAAAGGGGTCGCTGCACAGAAAGTTCCCCAAGCAGCGTCCTCAACAGGAGGATCTGGAGAACA
ACTCTGGGATATTTCGGTTCCTGCAGCACAAATTACAGAGGCTCTAGCTATTCTGAACCAAGCTGGGCTTCCAAGAATGAAAGGAACCAGCCTTCTTGAT
CTATTCGCTAAACAAGGGCTGGTCCCTTCTGAAATGCAAGAAAAAATCCGCTACCAAGAAGGTCTTTCAGAACAAATGGCTACGACCATTAGAAAGATGG
ACGGTATCGTCGATGCGAGCGTACAGATTTCCTTTTCTCCTGAAGAAGAAGATCAACGGCCGCTAACAGCCTCTGTATATATCAAACACAGAGGGGTATT
AGACAACCCTAACAGTATTATGGTGTCTAAGATTAAACGTTTAGTTGCGAGTGCTGTCCCAGGACTATGTCCCGAGAACGTTTCCGTAGTCAGTGACCGA
GCTTCTTATAGTGACATTACTATTAATGGCCCTTGGGGACTCTCCGATGAAATGAATTATGTTTCTGTATGGGGGATCATTCTAGCTAAGCATTCCCTTA
CTAAATTCCGCCTTGTTTTCTATTTCTTAATTCTCCTTCTCTTCATTCTTTCCTGTGGGCTACTCTGGGTCATTTGGAAAACACACACACTGATTTCTGC
TCTGGGTGGAACAAAAGGATTCTTTGATCCTGCTCCTTACTCACAGCTCTCTTTCACTCAGAATAAGCCAGCTCCAAAAGAAACTCCTGGAGCAGCAGAA
GGTGCAGAAGCGCAAACCGCTTCGGAACAACCCTCTAAAGAAAACGCAGAAAAACAAGAAGAGAATAACGAGGACGCTTAA
SEQ ID 201:
MSSKLVNYLRLTFLSFLGIASTSLDAMPAGNPAFPVIPGINIEQKNACSFDLCNSYDVLSALSGNLKLCFCGDYIFSEEAQVKDVPVVTSVTTAGVGPSP
DITSTTKTRNFDLVNCNLNTNCVAVAFSLPDRSLSAIPLFDVSFEVKVGGLKQYYRLPMNAYRDFTSEPLNSESEVTDGMIEVQSNYGFVWDVSLKKVIW
KDGVSFVGVGADYRHASCPIDYIIANSQANPEVFIADSDGKLNFKEWSVCVGLTTYVNDYVLPYLAFSIGSVSRQAPDDSFKKLEDRFTNLKFKVRKITS
SHRGNICIGATNYVADNFFYNVEGRWGSQRAVNVSGGFQF
SEQ ID 202:
ATGAGTAGCAAGCTAGTGAACTATCTCCGTTTGACTTTCCTATCTTTTTTAGGGATCGCATCTACTTCATTAGACGCTATGCCTGCGGGGAATCCGGCGT
TTCCAGTCATCCCGGGGATTAATATTGAACAGAAAAATGCCTGTTCTTTCGATTTATGTAATTCTTATGATGTACTATCCGCACTGTCCGGTAACCTGAA
GCTCTGCTTCTGCGGAGATTATATCTTTTCAGAAGAAGCTCAGGTAAAAGATGTCCCTGTCGTTACCTCTGTGACAACAGCTGGGGTTGGTCCTTCTCCT
GATATTACTTCGACAACCAAAACGCGAAATTTCGATCTCGTGAACTGTAATCTCAATACAAACTGTGTAGCTGTAGCTTTTTCCCTTCCTGATCGTTCGC
TGAGCGCGATTCCTCTGTTTGATGTGAGTTTCGAAGTGAAAGTAGGAGGACTGAAACAATACTACCGCCTTCCCATGAATGCCTATCGAGACTTCACCTC
GGAACCTCTCAATTCTGAATCAGAAGTTACGGACGGGATGATTGAAGTACAGTCCAATTACGGATTTGTTTGGGATGTTAGCTTGAAAAAAGTCATATGG
AAAGATGGCGTTTCCTTTGTAGGCGTCGGTGCAGACTATCGCCATGCTTCTTGCCCTATTGACTACATCATTGCAAACAGTCAAGCTAATCCAGAAGTAT
TCATCGCTGACTCGGATGGGAAACTGAACTTCAAGGAGTGGAGTGTCTGCGTAGGTCTTACTACCTATGTGAATGACTACGTTCTTCCTTACTTAGCGTT
TTCTATAGGGAGTGTTTCTCGCCAAGCTCCGGACGACAGCTTCAAAAAATTAGAAGATCGCTTCACTAACCTCAAATTTAAAGTTCGTAAAATTACCAGC
TCTCATCGTGGAAACATCTGCATCGGAGCGACAAACTATGTCGCCGATAACTTCTTCTACAACGTAGAAGGAAGATGGGGAAGCCAGCGCGCTGTGAACG
TCTCCGGAGGATTCCAATTCTAA
SEQ ID 203:
MPVLPRFLKNKIAYTKSLGYLLAAILIGFIMLYKPSSPQPTPTVASTEKKPSHWLKLSHLGNLQSIEIQAKKEQLEKDLTLFEPVLQATVALSQEEDSLA
EISVILSLPQASTLSPSLVHSITDYLTRSVPGLTKEHITLSDQHGNLYSPLFEQSNTLLTTSLERSLQTILPQTHFALNYIPVADEGHLQLLVDEDYLNT
LPKGARVKLLSHMQEILSAFPEMHPSVDIVPFLKPVAHKTSRLSSIVLSITIVLLSLGILGFATFYLAFHTYDHVSQQKEKIQSINIPKLIEMMKRESPE
KVALILSYLDSAKAEELLNKLPEEMKSAVLKLRT
SEQ ID 204:
ATGCCGGTGCTACCTCGCTTTCTAAAAAATAAGATCGCCTACACTAAATCTTTAGGCTACCTTCTTGCAGCTATTCTTATTGGCTTCATCATGTTGTATA
AACCATCCTCTCCTCAGCCTACCCCTACTGTAGCCTCTACAGAGAAAAAACCCTCACATTGGCTGAAGCTCTCCCATTTAGGGAATCTTCAATCGATAGA
AATCCAAGCAAAGAAAGAGCAATTAGAAAAAGATCTGACTCTATTTGAGCCTGTGCTCCAAGCAACGGTTGCTCTATCCCAAGAAGAAGACTCCTTAGCA
GAAATCTCCGTGATCCTTTCTCTTCCTCAGGCTTCGACATTATCCCCATCACTCGTGCACTCAATCACTGATTACCTGACACGCAGCGTCCCTGGGTTAA
CTAAAGAACATATCACCTTGTCCGATCAGCATGGTAATCTCTACTCCCCTCTCTTCGAACAAAGTAATACCCTACTCACTACCTCATTAGAACGCTCACT
ACAAACGATTCTTCCTCAAACGCATTTCGCCTTAAACTATATTCCTGTAGCGGATGAAGGCCATTTGCAACTTCTCGTCGATGAGGACTACCTCAATACT
CTTCCTAAAGGTGCACGTGTTAAGTTGCTCTCGCATATGCAAGAGATTCTCTCAGCATTCCCAGAAATGCATCCGTCTGTAGATATTGTCCCTTTCCTAA
AACCCGTAGCACACAAAACTTCTCGCCTATCCTCAATTGTCTTGAGTATTACTATTGTGTTACTAAGCCTTGGAATTCTAGGCTTTGCTACCTTCTATCT
TGCTTTTCATACCTATGACCATGTCTCTCAACAGAAAGAAAAAATACAGAGCATAAATATACCAAAGCTGATAGAGATGATGAAAAGAGAATCCCCAGAA
AAAGTTGCATTGATTCTCTCCTATCTAGACTCAGCAAAAGCGGAAGAACTTCTTAATAAACTTCCTGAAGAAATGAAGAGTGCTGTGTTAAAGTTAAGAA
CATAA
SEQ ID 205:
MLFWGIFSLCLGGLFGGYCRLRYTAKALLLSWRQLLRLALKKREVLQEIAALQTFPLLRLEEEIAFLKQGSFYSLKEFLKASDADGVTFYEMERFFTLRL
KQTLASLQESLHQEAVQHLMEELLAYENAFSFEAFAFEKAAETYATLHGHPVIQFSGKLFRFPQISFPPLDEAI
SEQ ID 206:
ATGCTTTTTTGGGGCATTTTTAGTTTGTGCTTAGGAGGGTTATTCGGGGGTTATTGTCGCTTGCGCTATACAGCAAAGGCTCTTTTGTTATCCTGGCGAC
AACTCCTTCGGCTTGCCTTAAAAAAAAGAGAGGTTTTACAAGAGATCGCAGCGTTGCAAACATTCCCTCTCCTTCGTTTAGAAGAGGAGATAGCCTTTTT
AAAGCAAGGCTCCTTCTATTCTTTGAAAGAATTTCTTAAAGCTAGTGATGCGGATGGAGTTACTTTCTATGAGATGGAACGATTTTTTACTCTCCGATTG
AAACAGACATTAGCATCGTTGCAAGAAAGTTTGCATCAAGAGGCTGTCCAGCATTTAATGGAAGAACTACTTGCGTATGAGAATGCGTTTTCTTTTGAGG
CCTTTGCTTTCGAAAAAGCCGCGGAAACCTATGCGACTCTTCACGGTCATCCGGTAATCCAATTTTCTGGGAAACTTTTTCGTTTTCCGCAAATCTCCTT
TCCGCCTTTAGATGAAGCGATATAG
SEQ ID 207:
MKKTKYLRQVNLWVFVVIILLMSISVIVISSQDPSSMLVHTSRGLFSAKSKKQLDHFALGWCAYFICLYVDYHQFKRWAWVLYSLILFSLIGLFFVPAVQ
NVHRWYRIPIINLSVQPSEYAKLVVVIMLSYILEMRKARISSKTTAFVACIIVGIPFLLILKEPDLGTALVLCPIALTIFYLGNIYPPLVKVCSVLVALG
MFCSLLIFSGIIPHDKVKPYALKVLKEYQYERLSPSNHHQRASLISIGVGGLKGQGWKSGEFAGRGWLPYGYTDSVFPAIGEEFGLLGLLFVLWLFYNLV
CFGCRTVAVAVDDFGRFLAGGVTVNLVMHVLINVSMMSGLLPITGVPLVLISYGGSSVISTMASLGILQSIYSRRFAKY
SEQ ID 208:
ATGAAAAAAACAAAATACTTGCGTCAAGTGAACTTGTGGGTCTTTGTAGTCATCATTCTACTTATGAGCATAAGTGTGATTGTGATCTCTTCTCAAGATC
CCTCTTCTATGTTAGTCCACACTTCACGAGGGCTGTTCTCTGCCAAAAGCAAAAAACAGTTGGATCACTTTGCTCTAGGATGGTGTGCCTACTTCATTTG
CTTGTATGTAGACTACCATCAATTCAAAAGATGGGCTTGGGTTCTCTATTCTTTGATTCTTTTCAGTCTTATTGGACTATTTTTCGTGCCCGCTGTACAA
AATGTACACCGCTGGTACCGCATACCCATTATTAATCTTAGCGTCCAACCTTCGGAATATGCCAAACTTGTCGTTGTCATTATGCTAAGCTATATTCTAG
AGATGCGCAAAGCACGGATTTCTTCTAAAACGACAGCATTCGTTGCATGTATTATTGTGGGGATTCCTTTTCTGCTTATCTTGAAAGAACCGGATCTGGG
AACAGCCTTGGTGCTATGCCCAATAGCCCTTACCATTTTTTATCTCGGAAATATCTATCCTCCACTAGTCAAAGTCTGTTCTGTGCTTGTCGCTTTGGGC
ATGTTCTGCTCTCTACTAATCTTCTCTGGGATTATCCCTCATGACAAGGTAAAACCTTACGCTCTTAAAGTATTAAAAGAATATCAGTACGAACGGCTCA
GCCCTTCCAACCATCACCAAAGAGCCTCTCTTATTTCCATTGGAGTAGGAGGGCTAAAAGGCCAAGGATGGAAATCTGGCGAATTCGCAGGGAGGGGCTG
GCTTCCTTACGGATATACAGACTCTGTGTTCCCTGCTATAGGAGAAGAATTCGGACTATTAGGACTCTTATTCGTATTATGGTTGTTTTACAACTTAGTC
TGTTTCGGCTGCCGTACTGTGGCTGTCGCGGTTGATGATTTTGGACGATTTTTAGCTGGAGGAGTGACCGTAAACCTGGTCATGCACGTACTTATCAATG
TCAGCATGATGAGTGGTCTCCTGCCTATTACCGGAGTCCCCTTGGTGTTAATTTCTTATGGAGGTTCTTCTGTAATTTCTACTATGGCTTCTTTAGGTAT
TTTACAAAGCATCTACAGTCGACGCTTTGCAAAATACTAA
SEQ ID 209:
MKKFIYKYSFGALLLLSGLSGLSSCCANSYGSTLAKNTAEIKEESVTLREKPDAGCKKKSSCYLRKFFSRKKPKEKTEPVLPNFKSYADPMTDSERKDLS
FVVSAAADKSSIALAMAQGEIKGALSRIREIHPLALLQALAEDPALIAGMKKMQGRDWVWNIFITELSKVFSQAASLGAFSVADVAAEASTLGLDSGTVT
SIVDGERWAELIDVVIQNPAI
SEQ ID 210:
ATGAAAAAGTTTATCTATAAGTATAGCTTTGGAGCTCTCTTGTTGCTCTCCGGGCTCTCCGGATTGAGCAGCTGTTGCGCCAACTCTTATGGATCGACTC
TTGCAAAAAATACAGCCGAGATAAAAGAAGAATCTGTTACACTTCGCGAGAAGCCGGATGCCGGCTGTAAAAAGAAATCTTCTTGTTACTTGAGAAAATT
TTTCTCGCGCAAGAAACCTAAAGAGAAGACAGAGCCTGTGTTGCCGAACTTTAAGTCTTACGCAGATCCAATGACAGATTCCGAAAGAAAAGACCTTTCT
TTCGTAGTATCTGCTGCTGCTGATAAGTCTTCTATTGCTTTGGCTATGGCTCAGGGGGAAATTAAAGGCGCATTATCGCGTATTAGAGAGATCCATCCTC
TTGCATTGTTACAAGCTCTTGCAGAAGATCCTGCTTTAATTGCTGGAATGAAAAAGATGCAAGGACGGGATTGGGTCTGGAATATCTTTATCACAGAATT
AAGCAAAGTTTTTTCTCAAGCAGCATCTTTAGGGGCTTTCAGCGTTGCAGACGTTGCCGCGTTCGCGTCGACCTTAGGATTAGACTCGGGGACCGTTACC
TCAATTGTTGATGGGGAAAGGTGGGCTGAGCTGATCGATGTCGTGATTCAGAACCCTGCTATATAA
SEQ ID 211:
MNIYRFISGSCSWFLIGWGICFGADVPLSFGHQCADVRKAMQEGKPLLPIFDAFIRRIVNDSSSLSEKDWETATWLICEYIRGSLKRGEQELCSELVKPL
FSLAVMPPQSKARIKQVWQVLNPQGASLKDLVRLLESSGCSSSPQDHLLLSLYNMTLHSSYENKKAEILFAREQKNYQDALRLCEELQENLTSGLCSPLS
TVYEVEQAFLKRISLAIRWEQEKELQGSPSIELLLAYCSAEESYAEAVEQLIKKIELGSLDRSQEVDALLFAHALSKLPWEETLGEHELEVLISGGHYLT
SIYSQHAYFSLLEQYFKKSQIQEISRLLDFGKTVFVETHKKYPEYLFFLGKYWFYLRDFSRAEEAFSSVIRYADRLGVSLAETYEYLGCLACYKGHYASA
KEFFLKAYKGWGREDAGIGLYLLAVLEKDPILCQQVREQVSLSFSHQEFLKWMDRNFLPEPGKEGSSFFKVLGSSRSLSEEEFHGLLLKEMISRHHREKL
SCSPIQRLVYDQLDREIQLRLTETLIQTEDLLVRRKLSLWRALYEGSLVSWGSAHQNQTLFEKSILQCFSALSQQDPSAIQQIAEAFSSGASLWQSSLRM
VWAVSHTSENPISKAYSLGISDRPWGDRLYLLQYSLEQYLSGDTELLEYLTQFPELFPNSPLLPLVYYLQARGEGDPIRKIAWLTKALETFTENSLLAKE
MKAWAPLYYLMRMDLAETYLYLGNVSKSQTLFEAIQEEWDAPHHPYVKLIDPPHIRVSLEMRWVSGLAHVYEAIQATEQRNALLISHIEKRFFQMRPRQE
YIGKMLTFTSSLCRELLADAS
SEQ ID 212:
ATGAATATTTATAGATTCATCTCTGGAAGCTGTTCATGGTTTCTGATAGGTTGGGGGATATGCTTCGGAGCTGACGTGCCACTTTCTTTTGGGCACCAAT
GCGCAGACGTTCGCAAGGCGATGCAAGAGGGCAAGCCGCTTTTGCCTATTTTTGATGCGTTTATTCGTCGTATCGTGAATGACAGCTCATCTTTATCTGA
GAAAGATTGGGAAACAGCAACATGGTTAATTTGTGAATATATACGAGGGAGTTTAAAGCGGGGAGAACAAGAGTTATGCTCGGAGCTTGTAAAACCTCTG
TTTTCTTTAGCTGTAATGCCTCCGCAGTCAAAAGCTCGTATTAAGCAAGTGTGGCAGGTACTCAATCCTCAAGGAGCTTCTTTAAAGGACTTAGTCCGTT
TACTGGAAAGTAGCGGATGCTCCTCTTCACCGCAAGATCATCTCCTACTTTCTTTATATAATATGACACTGCATAGCAGTTATGAGAACAAGAAAGCAGA
GATCCTTTTTGCAAGAGAACAAAAAAATTATCAGGACGCTTTACGTTTATGCGAGGAGTTGCAAGAAAATCTGACTTCAGGGCTTTGTTCACCTCTTTCA
ACGGTATATGAGGTGGAGCAAGCCTTCTTAAAGCGAATCTCCTTAGCCATACGGTGGGAACAAGAGAAGGAGCTGCAAGGGAGCCCCTCTATAGAGTTGC
TATTGGCCTATTGTAGTGCGGAAGAGAGTTACGCAGAGGCTGTGGAGCAGTTAATCAAAAAAATAGAATTAGGAAGCTTAGACCGATCACAAGAAGTCGA
CGCAATTTTATTTGCACATGCGTTAAGTAAACTTCCATGGGAAGAGACTCTTGGAGAACACGAACTGGAGGTTCTCATATCAGGAGGACACTATCTCACA
TCGATTTATTCTCAACATGCTTACTTTTCGCTTCTCGAACAATATTTTAAAAAATCTCAAATACAAGAAATATCTCGCTTATTAGATTTTGGGAAAACCG
TCTTTGTTGAGACCCATAAGAAATATCCGGAATACCTCTTCTTTCTAGGCAAGTACTGGTTTTACTTGCGGGATTTCTCTCGTGCAGAAGAGGCTTTTTC
TTCTGTAATTCGGTATGCAGATCGACTGGGAGTGTCTTTAGCGGAAACTTATGAGTATTTAGGGTGTTTAGCTTGTTACAAAGGGCACTATGCTTCCGCT
AAAGAATTCTTTCTTAAAGCTTACAAGGGGTGGGGGAGAGAGGATGCCGGTATAGGATTGTATCTATTGGCAGTCTTAGAAAAAGATCCTATTTTATGTC
AGCAGGTCAGAGAACAGGTGTCTTTATCCTTTTCACATCAGGAATTTTTAAAATGGATGGATAGAAATTTCTTACCTGAGCCAGGGAAAGAAGGCTCTTC
TTTTTTTAAGGTATTGGGAAGCTCGCGTTCTTTATCTGAAGAAGAGTTTCATGGATTACTGCTAAAGGAGATGATTAGTCGTCATCATAGAGAGAAGCTC
TCTTGCTCTCCTATACAACGGCTAGTGTACGACCAGTTGGATCGAGAGATACAACTTCGGTTGACAGAAACATTAATTCAAACAGAAGATCTTCTGGTGA
GACGCAAGCTCTCTTTATGGAGAGCTCTATATGAAGGATCGTTGGTATCTTGGGGGTCTGCTCATCAGAATCAGACTTTATTTGAGAAAAGTATTTTGCA
GTGTTTTTCTGCTCTGTCGCAGCAGGACCCTAGCGCAATACAGCAAATAGCAGAAGCTTTTTCTTCAGGAGCCTCTTTATGGCAATCCTCTTTGAGGATG
GTGTGGGCAGTTAGTCATACTAGTGAAAATCCTATATCGAAGGCATATTCGTTAGGCATATCTGATCGGCCTTGGGGAGATCGACTGTATCTTTTACAGT
ATTCATTAGAGCAATATCTTTCTGGAGATACAGAATTATTAGAGTATTTAACACAATTCCCAGAATTATTCCCGAACTCGCCTTTGTTGCCTTTGGTTTA
TTATTTGCAGGCAAGAGGTGAGGGAGATCCAATTCGAAAGATCGCTTGGTTAACAAAAGCTTTAGAGACTTTTACGGAAAATTCTTTGTTAGCAAAGGAG
ATGAAAGCTTGGGCTCCTTTGTATTATTTAATGCGAATGGATTTAGCAGAAACCTACCTATATTTAGGGAATGTGTCTAAATCACAAACTCTTTTCGAAG
CGATCCAAGAAGAGTGGGATGCTCCGCACCATCCTTATGTAAAGTTGATAGATCCGCCGCACATCCGTGTGTCTTTGGAGATGCGTTGGGTTTCGGGGCT
TGCTCATGTGTATGAAGCTATACAAGCAACTGAACAAAGAAATGCGTTATTAATCAGCCACATTGAAAAACGTTTCTTTCAAATGCGACCAAGACAGGAA
TATATTGGGAAGATGTTAACATTCACGAGTTCTCTATGCAGAGAACTATTAGCAGATGCCTCATGA
SEQ ID 213:
MNRRNTMIVATAVNAVLLAVLFMTARHSEQEIEYSQKIAPIKILEPVPVVDKAPEKLEKKPEVIAKPSQVVRNPVVSKAELAAQFADKNPKTEKESSGGS
KEISSTPVESTTPVAPEISVVNAKVVEKTPEKEEFSTVIVKKGDFLERIARSNHTTVSALMQLNDLSSTQLQIGQVLRVPKTNKTEKDLQVKTPNLEDYY
VVKEGDSPWAIALSNGIRLDELLKLNGLDEQKARRLRPGDRLRIR
SEQ ID 214:
ATGAATCGTAGAAACACGATGATTGTAGCAACTGCTGTGAATGCAGTGCTATTGGCAGTGCTGTTTATGACCGCGCGCCATTCAGAGCAAGAAATAGAGT
ATTCTCAGAAAATAGCTCCTATTAAAATCTTAGAGCCCGTTCCGGTTGTTGATAAGGCTCCAGAGAAGTTAGAGAAAAAGCCTGAGGTGATTGCGAAGCC
TTCTCAGGTCGTTAGAAATCCTGTCGTTTCTAAAGCTGAACTTGCTGCGCAATTTGCAGACAAAAATCCTAAGACAGAGAAGGAATCTAGCGGGGGCTCT
AAAGAGATTTCATCTACCCCTGTAGAATCGACGACTCCTGTCGCTCCAGAAATTTCTGTTGTGAACGCTAAGGTAGTAGAGAAAACTCCTGAAAAAGAGG
AATTCTCTACTGTTATTGTTAAGAAAGGAGACTTTTTAGAACGTATAGCTAGATCCAATCACACTACAGTTTCTGCATTGATGCAGTTGAATGACTTATC
TTCGACACAGTTACAGATAGGACAAGTGTTACGAGTTCCTAAAACGAATAAGACAGAGAAGGATCTTCAAGTGAAGACTCCAAATCTGGAAGATTACTAT
GTAGTCAAGGAAGGAGATAGTCCTTGGGCCATTGCATTGAGTAATGGTATTCGTTTGGATGAGCTGTTGAAGTTAAATGGATTAGATGAGCAGAAAGCTC
GTAGATTACGTCCAGGGGATAGATTACGAATTCGATAA
SEQ ID 215:
MKWFLISCLLGIFSLGLIMVFDTSSAEVLDRALSCSTHKALIRQITYLGLGLGIASFVYILGWKDFLKMSPMLLIFVGITLVLVLIPGIGVCRNGAKRWL
GVGQLTLQPSEFVKYLVPCVAIECLTTKPSIRSSFKRFVAFVALLFIPIMLIAIEPDNGSAAVISFSLIPVFIVTAVRLRYWLLPLLCILCIGGTFAYRL
PYVQNRLQVYLHPELDIKGRGHQPYQAKIAAGSGRVFGKGPGKGLQKLTYLPEAQNDYIAAIYAEEFGFIGMLLLILLYMGFIYSGYVIAMRASLLSGAA
LAISITVIIGMQAFINLGVVSGLLPSKGVNLPFFSQGGSSLIANMCGMGLLLRICDEENQQNRIGSGGNRRAHYPCSSSKRDFYS
SEQ ID 216:
ATGAAATGGTTCCTGATTTCCTGTTTATTAGGAATTTTTTCTCTCGGGCTGATCATGGTGTTTGATACCTCATCAGCAGAGGTTTTGGATCGAGCTTTGT
CGTGTAGTACACACAAAGCTCTGATCCGGCAGATTACTTATCTTGGATTGGGACTTGGTATCGCTTCATTTGTGTACATCTTAGGATGGAAGGATTTCTT
GAAAATGAGCCCTATGTTGCTGATTTTCGTGGGGATTACTCTTGTTTTGGTTCTTATTCCAGGTATTGGTGTTTGTAGAAATGGAGCTAAGCGTTGGCTA
GGAGTGGGGCAGTTAACTTTACAGCCTTCTGAATTTGTTAAATATTTAGTTCCATGTGTTGCTATCGAATGTTTAACAACAAAACCTTCTATTCGTAGTA
GTTTTAAACGATTCGTAGCTTTCGTTGCTCTGTTGTTTATCCCCATTATGTTGATAGCGATTGAACCTGACAATGGATCTGCGGCCGTGATCTCATTTTC
CTTAATTCCAGTTTTTATCGTAACTGCAGTGCGATTACGCTATTGGCTGCTTCCTTTGCTATGTATTCTGTGTATTGGAGGTACATTTGCCTATCGGCTC
CCTTATGTTCAGAATCGTTTGCAAGTTTACCTACATCCTGAATTAGATATTAAAGGAAGAGGCCATCAACCTTACCAAGCTAAAATTGCAGCAGGCTCTG
GAAGAGTGTTTGGTAAAGGTCCAGGAAAAGGATTACAAAAATTAACTTATCTTCCAGAAGCTCAGAATGATTACATTGCTGCTATTTACGCAGAAGAGTT
TGGATTTATTGGGATGCTCCTATTGATTCTTCTCTACATGGGATTTATTTATAGCGGGTATGTCATTGCAATGCGAGCCTCCCTTTTATCTGGAGCGGCT
CTTGCTATTTCAATCACTGTGATTATTGGGATGCAAGCTTTTATTAACTTGGGTGTTGTTTCTGGGTTATTGCCTAGCAAGGGAGTGAACCTTCCATTTT
TTAGTCAGGGAGGCTCTTCTCTAATTGCTAATATGTGTGGCATGGGATTGCTATTAAGGATATGTGATGAAGAAAATCAACAAAATCGTATTGGCAGTGG
GGGGAACAGGAGGGCACATTATCCCTGCTCTAGCAGCAAGAGAGACTTTTATTCATGA
SEQ ID 217:
MKKINKIVLAVGGTGGHIIPALAARETFIHEDIEVLLLGKGLAHFLGDDSEVAYCDIPSGSPFSLRVNRMFSGAKQLYKGYVAALQKIRDFTPDLAIGFG
SYHSLPAMLASIRSRIPLFLHEQNIVPGKVNKLFSRFAKGVGMSFAAAGEHFHCRAEEVFLPIRKLSEQIVFPGASPVICVVGGSQGAKILNDVVPKALA
RIRESYSNLYVHHIVGPKGDLQAVSQVYQDAGINHTVTAFDHNMLGVLQASDLVISRSGATMLNELLWVQVPAILIPYPGAYGHQEVNAKFFTHTVGGGT
MILQKYLTEESLSKQVLLALDPATSENRRKAMLSAQQKKSFKSLYQFICESL
SEQ ID 218:
ATGAAGAAAATCAACAAAATCGTATTGGCAGTGGGGGGAACAGGAGGGCACATTATCCCTGCTCTAGCAGCAAGAGAGACTTTTATTCATGAAGACATAG
AAGTCTTACTTTTAGGGAAAGGATTAGCTCATTTTTTAGGGGATGATTCAGAGGTCGCCTATTGTGATATCCCTTCAGGATCGCCTTTTTCTTTGCGTGT
CAATCGGATGTTCTCTGGGGCTAAGCAGTTATATAAAGGTTATGTCGCAGCTCTACAAAAGATCAGAGATTTTACTCCTGATTTAGCAATAGGATTTGGG
AGTTACCATTCCTTACCTGCTATGCTTGCTTCTATAAGAAGTAGGATTCCTCTTTTTCTGCATGAACAGAATATTGTTCCTGGGAAAGTGAATAAGTTAT
TTTCACGTTTTGCTAAAGGTGTAGGGATGTCTTTTGCAGCAGCAGGGGAACATTTCCATTGCCGAGCCGAAGAAGTCTTTCTCCCTATCAGGAAACTGTC
TGAGCAGATCGTTTTCCCTGGAGCTTCTCCTGTCATTTGTGTGGTAGGAGGATCCCAAGGAGCAAAAATTTTAAATGATGTTGTTCCAAAAGCCTTGGCT
CGTATTCGAGAAAGTTATTCGAATTTATATGTTCATCATATTGTAGGGCCTAAAGGAGACCTTCAAGCGGTTTCTCAAGTTTATCAAGATGCTGGTATCA
ATCATACAGTTACCGCATTTGATCACAATATGCTCGGCGTACTACAGGCAAGCGATTTAGTGATTAGTAGATCTGGAGCAACGATGCTTAATGAGTTGCT
TTGGGTTCAGGTGCCTGCCATTCTTATTCCTTATCCAGGTGCTTATGGACATCAAGAAGTGAATGCAAAATTCTTCACGCATACTGTAGGTGGAGGGACT
ATGATTTTGCAGAAGTATTTAACAGAAGAAAGTTTGAGTAAGCAGGTTTTACTTGCTTTAGATCCTGCAACCAGTGAAAATAGGCGCAAGGCTATGCTTT
CCGCACAACAGAAGAAGTCTTTCAAATCACTGTATCAGTTTATTTGTGAATCTCTATAG
SEQ ID 219:
MMKSLFYHFIGIGGIGMSALAHVLLDRGYSVSGSDLSEGKVVEKLKNKGAEFFLGNQEEHIPEGAVVVYSSSISKKNPEFLSAKSRGNRVVHRAELLAEL
AQDQISIFVTGSHGKTTVSSLITAILQEAKKNPSFAIGGLNQEGINGGSGSEYFVAEADESDGSIRCYTPEFSVITNIDDEHLSNFEGDRELLLASLKDF
ALKTQQICWYNGDCPRLRSCLQGHTFGLDSSCDLHILSYYQEGWRLYFTAKYQDVVYADIEVQLVGMHNVLNAAAAMGIALSLGIDEGAIRNAFRGFSGV
QRRLQRKNSSETFLFLEDYAHHPSEISCTLRAVRTAVGQRRILAIYQPHRFSRLRECIDSFPSAFKDADEVLLTEVYSAGEEAEDISYQKLAEAISQESI
VKCTHIPFHELQRHLEQSIRVHDVCVSLGAGNIVNLGEKLRDFEPQKLHLGIICGGKSCEHEISVLSAKNIAKHLSKSFYDVSYFLITREGLWESVSSLE
TAEDSGKSVFDPEIAQRLEKVDVVLPILHGPYGEDGAMQGFLETIGKPYTGPAIAFSAIAMNKVFTKRFMSDLGIPVVPYLPLTLAGWKQEQDKWLAHIV
EAFSFPIFVKSSHLGSSIGVFEVHNVIELRDAINEAFMRDNDVFVEENRLGCKEIEVSVLGDGSGAFVVAGLHERRGSGGFIDYQEKYGLSGKSSAQIVF
DTDLSKEIQEQILEAADKIYRLLLGKGSCRIDFFVDEEGNFWLSEMNPIPGMTETSPFLTSFIRKGWSYEQIVHQLVIDGLQRFNQRQRLISTSFVDQAF
AIQ
SEQ ID 220:
ATGATGAAAAGCTTGTTTTACCACTTTATTGGTATTGGTGGGATTGGAATGAGTGCTTTAGCACATGTTCTGCTCGATCGAGGATATAGCGTATCGGGAA
GTGATCTTTCCGAGGGGAAAGTGGTAGAGAAGCTGAAGAATAAAGGAGCGGAATTCTTTTTAGGGAATCAAGAAGAACATATCCCTGAAGGCGCTGTAGT
TGTATACAGTTCAAGTATTTCTAAAAAAAATCCTGAATTTTTATCAGCTAAAAGTAGAGGGAACCGCGTAGTTCATCGAGCCGAATTATTAGCCGAGCTT
GCTCAAGATCAGATTTCTATTTTTGTTACAGGAAGTCATGGAAAGACAACAGTCTCTTCTTTAATTACAGCCATTTTGCAGGAAGCGAAGAAAAATCCGT
CCTTTGCTATAGGAGGTTTGAATCAAGAAGGCATCAATGGTGGTTCGGGATCGGAATATTTTGTTGCTGAAGCAGATGAGAGCGATGGGTCTATTCGGTG
TTATACTCCAGAGTTTTCTGTTATTACGAATATAGATGATGAGCATCTGTCTAATTTTGAAGGAGATCGAGAGCTTCTTCTGGCTTCTTTGAAAGACTTT
GCACTCAAGACTCAGCAGATCTGTTGGTATAATGGAGATTGTCCTCGCTTGCGTTCATGCTTGCAAGGGCATACTTTTGGATTGGACTCTTCTTGTGATC
TACATATTCTATCTTATTATCAAGAAGGATGGAGACTGTACTTTACAGCAAAGTATCAAGATGTAGTGTATGCAGATATAGAAGTGCAATTGGTCGGCAT
GCATAACGTTTTGAATGCTGCAGCAGCTATGGGAATAGCTCTGTCATTGGGTATAGATGAAGGTGCTATAAGAAATGCTTTCAGAGGGTTTTCAGGAGTT
CAAAGACGATTACAAAGAAAGAATTCTTCTGAGACCTTTCTCTTTTTAGAAGATTATGCACACCATCCTTCAGAGATTTCTTGTACATTACGTGCTGTTC
GTACTGCTGTTGGACAGAGACGTATTTTAGCTATTTACCAGCCTCATCGTTTTTCTCGATTAAGAGAGTGTATAGACAGCTTCCCGTCAGCATTTAAAGA
TGCTGATGAAGTCTTGTTAACAGAAGTGTACAGTGCAGGAGAGGAGGCGGAAGATATTTCGTATCAGAAGCTTGCTGAAGCTATTAGTCAAGAGTCGATA
GTAAAGTGTACGCATATTCCGTTTCATGAGTTGCAGAGACATTTAGAGCAGTCCATCCGTGTACACGATGTGTGTGTATCTTTAGGTGCTGGTAATATTG
TGAATTTGGGAGAAAAGTTAAGAGATTTTGAGCCTCAAAAACTGCACTTAGGAATTATTTGTGGAGGGAAATCATGCGAACACGAGATTTCCGTTCTATC
TGCAAAAAATATAGCTAAACATCTTTCAAAATCCTTTTATGATGTGAGTTATTTTTTAATTACTCGAGAAGGATTATGGGAGAGCGTCTCTTCATTAGAG
ACTGCTGAAGACTCAGGGAAATCCGTTTTTGATCCAGAAATAGCTCAGAGACTAGAAAAAGTAGACGTAGTGTTGCCGATACTACATGGTCCCTATGGTG
AAGATGGAGCTATGCAAGGATTTCTAGAGACTATTGGCAAGCCTTATACAGGTCCTGCTATCGCTTTTTCTGCGATAGCAATGAATAAAGTGTTTACTAA
GCGTTTTATGAGTGATTTAGGGATTCCTGTCGTTCCTTATCTCCCTTTAACATTAGCAGGATGGAAGCAAGAACAAGATAAGTGGTTAGCACATATTGTA
GAGGCTTTTTCATTTCCTATATTTGTGAAATCTTCGCATTTAGGATCTAGTATCGGCGTCTTCGAAGTTCATAATGTTATAGAATTACGAGATGCCATTA
ATGAAGCTTTTATGCGAGATAACGACGTGTTTGTAGAAGAAAATCGCTTAGGTTGCAAAGAAATAGAAGTTTCTGTCTTAGGAGATGGATCTGGTGCGTT
TGTCGTTGCTGGTCTGCATGAGCGTCGTGGGAGTGGAGGTTTTATAGACTATCAAGAGAAGTATGGGTTAAGTGGTAAGTCTAGTGCGCAGATCGTATTT
GATACAGATCTCTCTAAAGAAATACAGGAACAAATACTAGAAGCTGCGGATAAAATTTACCGTTTATTGCTAGGGAAAGGGTCGTGTCGTATTGACTTTT
TTGTAGATGAAGAAGGAAATTTCTGGTTATCTGAGATGAACCCCATTCCTGGAATGACAGAAACGAGCCCATTTCTTACATCTTTCATTCGTAAAGGGTG
GAGTTATGAACAGATAGTCCATCAACTTGTTATTGATGGGCTGCAACGATTTAACCAACGCCAACGCTTGATATCGACGTCTTTTGTAGATCAAGCGTTC
GCTATTCAGTAA
SEQ ID 221:
MRNWLLGSLLIACMAVTAPCFAAKRRAAGSQKINRVAETGIHWMSYQDALNKAKQEGKHVAVFFTGSDWCIWCMRMQDQILQTAAFSEFAKQYLCMVEID
FPHNKEQTAEQKEQNRHLKSLYSVDGFPTLVLLDSEGKEVAKMGFEPGGGEAYVYRLKKALHIS
SEQ ID 222:
ATGAGAAACTGGTTATTAGGGAGCTTGCTCATCGCATGTATGGCGGTCACAGCTCCTTGTTTTGCTGCAAAACGTCGTGCTGCGGGTTCGCAGAAGATCA
ATAGGGTTGCAGAGACCGGAATTCACTGGATGTCTTATCAAGATGCTTTGAATAAGGCAAAACAGGAAGGAAAGCATGTAGCCGTATTTTTCACAGGATC
CGATTGGTGTATTTGGTGTATGAGAATGCAGGATCAGATTTTACAAACAGCTGCATTTTCCGAGTTTGCTAAACAATATTTGTGTATGGTGGAGATAGAT
TTCCCTCACAACAAAGAACAAACTGCAGAACAAAAAGAGCAGAATCGTCATTTGAAAAGTTTATATTCTGTAGACGGATTCCCCACCCTAGTTTTACTCG
ATTCCGAAGGTAAAGAAGTCGCAAAAATGGGATTTGAGCCTGGAGGCGGAGAGGCATATGTTTATAGATTAAAGAAAGCATTACATATCTCCTGA
SEQ ID 223:
MNSGMFPFTFFLLYICLGMLTAYLANKKNRNLIGWFLAGMFFGIFAIIFLLILPPLPSSTQDNRSMDQQDSEEFLLQNTLEDSEIISIPDTMNQIAIDTE
KWFYLNKDYTNVGPISIVQLTAFLKECKHSPEKGIDPQELWVWKKGMPNWEKVKNIPELSGTVKDE
SEQ ID 224:
ATGAACTCCGGAATGTTCCCATTCACCTTTTTTTTACTGTACATCTGTCTGGGAATGCTTACGGCGTACCTAGCTAATAAAAAAAATCGCAATCTAATAG
GCTGGTTTTTGGCAGGAATGTTTTTTGGTATTTTTGCCATTATCTTCCTATTAATTCTCCCTCCTCTTCCTTCTTCTACACAAGATAATCGTTCCATGGA
CCAGCAAGATTCCGAAGAATTCCTTTTACAGAATACTTTAGAGGACTCAGAAATTATTTCCATCCCAGATACAATGAATCAAATTGCGATTGATACAGAA
AAGTGGTTCTACTTAAATAAAGACTATACTAATGTCGGTCCTATTTCCATCGTACAGCTGACCGCATTCTTAAAAGAATGCAAACACTCTCCTGAAAAAG
GGATCGATCCCCAAGAATTATGGGTATGGAAGAAAGGAATGCCTAACTGGGAAAAGGTGAAGAATATACCGGAACTTTCAGGAACAGTAAAAGACGAGTA
A
SEQ ID 225:
MDNHPPVINDPTNDPKNMKRSLSLLLLCIPSFLTACSKSFQTIRDENPLTILTPALADQKTAKILCPNGLSLMIVSSPHAAESGAALVVKTGNNADPVEF
PGLAHFTEHCVFLGNEKYPEPSGFPAFLSTHGGIYNAFTYPDKTCFLFSVNNADLDNALDQFVHLFIQPLFRQEDLNKEVHAVEQEFAMHPTKDSRRMHR
IQQLIAPKNHPLKRFGCGNLSTLNSVTTQDMQTWFATHYSPENMAAIVYTTAPLDTAVPYIASLFSEIPISAQYTPQKPFPKTQDTTALNKLFINKAVEP
SPQLAIYWHFYDAPQSLQGWAQSLISILSSEKENSLVALLKKEQLITEMEAELYSTSHNTQDFEILYKLTNKGEREYQRVLQLTFAFLDYVRHERLPAYS
LPEIQKINSLEYTYSTQTELFSTLSRMVPNFTSEPLATYPYRSLVYPEYSQEDEQTFATFLADPQQARYILSATLPSSWENADEFYDPIFDDTFYEKPLD
FTPIQDSSSLGFAFPNPNKFIPQTVQLLSQKKQHEGFAFSPQLTYDQNAITLYTCEDSFYTIPKMAMELRIRSPQIQRTDVRSLVLRDLYSLLANETLIK
RYDDALKAGMTFAVSPGATGVDLSLLGYTETSPVLINALLSSLRDLPVEESLFLYYKDQLSEQYQKNLIACPIRAGLNKLYSQILVDTVSLEDKLNTLNT
LSYEEFANFTNKLLQELAVESLALGTLSAQDLSNLLSTLSNFAEASSPYAAPSYYPQRKPLSSTKLSFQYPLSGNGMLLLEQNEDPHQYKDSVATSMLLS
WIHNLYFSDLRTEQQLGYMVGSKYLEFAETPCGLFYIRSNNYSPEELVHRTQLFIQKIATDPESAGLSEEIFEQLTETYIQSILLPSSTPLAMAKKLFSI
AFETKKQDFSRPDQKIAAARSMDYSYFKKYCEEFLSQKFGPEIQLLVYGANSSQEK
SEQ ID 226:
ATGGACAACCACCCTCCTGTTATCAATGACCCTACCAATGACCCCAAAAATATGAAGCGTTCCCTATCCCTATTACTTCTTTGCATTCCTTCTTTTCTAA
CTGCTTGCTCGAAATCCTTTCAAACGATTCGAGATGAAAATCCTTTGACTATTTTGACCCCTGCATTAGCAGATCAAAAAATTGCTAAAATTCTATGCCC
TAACGGACTCTCTCTCATGATTGTATCCTCCCCTCATGCTGCTGAGTCCGGAGCCGCTTTAGTTGTCAAAACAGGAAATAATGCAGATCCTGTCGAGTTC
CCAGGCTTAGCCCATTTTACAGAACACTGTGTGTTCCTCGGGAATGAAAAATATCCCGAGCCCTCAGGATTTCCTGCCTTCCTAAGCACACATGGGGGTA
TCTATAACGCATTTACTTACCCAGATAAAACCTGCTTCCTATTCTCCGTAAACAATGCAGATTTAGATAATGCTCTGGATCAGTTTGTACATCTCTTTAT
CCAACCTCTCTTCCGCCAAGAAGATTTAAACAAAGAAGTTCATGCTGTTGAGCAAGAATTTGCGATGCATCCAACTAAAGATTCTCGTCGTATGCATCGT
ATTCAACAACTTATAGCTCCTAAAAATCACCCATTAAAACGCTTTGGCTGCGGCAATCTCTCTACCCTCAACTCCGTCACTACTCAAGATATGCAAACAT
GGTTTGCCACTCACTACTCTCCAGAAAATATGGCAGCAATTGTTTACACTACAGCTCCGTTGGACACCGCAGTGCCGTATATCGCGTCCCTATTCTCTGA
AATCCCTATATCTGCACAGTACACACCACAAAAACCGTTTCCAAAGACACAGGATACTACTGCTCTTAATAAACTGTTCATCAATAAGGCTGTCGAACCT
TCTCCACAACTAGCTATTTACTGGCATTTTTATGATGCTCCACAGTCCTTACAAGGATGGGCTCAGTCACTGATTTCTATTTTATCTAGTGAAAAAGAAA
ATAGTCTTGTTGCTTTACTCAAAAAAGAACAGCTCATTACTGAGATGGAAGCAGAACTTTACAGCACTTCTCATAATACACAAGATTTTGAAATTCTTTA
TAAACTCACCAATAAGGGGGAACGCGAATATCAAAGAGTTTTGCAGCTAACTTTTGCTTTTCTTGATTATGTTCGTCATGAACGACTTCCTGCCTACTCC
TTGCCAGAGATACAGAAAATCAACTCTTTAGAATATACTTACAGCACGCAAACCGAGTTATTCTCGACACTATCACGAATGGTCCCCAATTTTACTTCTG
AACCATTAGCAACATACCCTTATCGCTCTCTTGTCTATCCAGAATACTCCCAAGAAGATGAACAAACCTTTGCTACATTTTTAGCAGACCCTCAACAGGC
ACGTTATATCTTATCTGCTACCCTACCGAGTTCTTGGGAGAATGCAGATGAATTCTATGATCCCATCTTTGACGACACTTTCTATGAAAAACCCTTAGAT
TTCACACCTATACAGGACTCCTCCTCCTTAGGATTTGCTTTTCCGAATCCCAATAAATTTATTCCTCAAACAGTCCAATTATTATCTCAAAAGAAACAAC
ACGAAGGGTTTGCTTTTTCTCCGCAGCTGACCTATGATCAAAATGCGATCACTTTATATACTTGTGAAGACTCTTTCTATACGATTCCTAAAATGGCTAT
GGAGTTGCGCATCCGTTCTCCTCAAATTCAACGAACAGATGTGCGTTCTTTAGTATTACGAGACCTATATAGTCTACTAGCTAATGAAACATTAATAAAA
CGTTATGACGATGCTTTAAAAGCTGGAATGACTTTTGCAGTATCTCCTGGAGCGACAGGGGTTGATCTTTCTCTTTTAGGATATACTGAGACCTCTCCTG
TTCTTATCAATGCTTTGCTGTCTTCTTTACGAGATCTTCCTGTGGAAGAAAGTCTGTTTCTATATTACAAAGATCAGCTATCAGAACAATATCAGAAGAA
TCTTATTGCCTGCCCTATAAGAGCTGGTCTCAATAAACTATACTCTCAGATTCTTGTTGATACCGTTTCCTTAGAAGATAAGCTCAATACTTTAAACACC
CTCTCCTACGAAGAGTTTGCGAACTTCACGAATAAACTACTCCAAGAACTAGCTGTAGAATCTTTAGCACTAGGAACGCTCTCGGCTCAAGATCTCTCCA
ATTTATTATCGACTCTCTCTAACTTTGCAGAAGCTTCGTCTCCTTATGCTGCTCCTAGCTATTATCCTCAAAGAAAACCTCTCTCTTCTACAAAGCTTTC
GTTCCAATATCCTCTCTCTGGAAATGGTATGCTGCTGCTCGAACAAAACGAAGATCCCCATCAATATAAGGACTCTGTAGCTACTAGTATGTTGTTATCT
TGGATCCATAACTTGTACTTCTCTGATTTACGTACAGAGCAACAACTTGGGTATATGGTAGGTTCTAAATATCTGGAATTCGCAGAAACTCCTTGTGGAC
TTTTCTATATTCGATCCAATAACTATTCTCCTGAGGAGCTTGTGCATAGAACACAACTCTTTATACAAAAGATTGCTACTGATCCAGAATCTGCAGGCTT
GTCCGAAGAGATCTTTGAACAGCTTCGAGAAACATATATCCAGTCCATATTGCTTCCAAGTTCCACACCTTTAGCTATGGCGAAAAAATTATTCTCTATA
GCTTTTGAAACGAAAAAACAGGATTTTTCTCGCCCAGACCAAAAAATAGCTGCTGCCCGTTCTATGGATTACAGCTATTTCAAAAAGTACTGTGAAGAAT
TTTTGAGTCAAAAGTTTGGCCCAGAAATCCAACTCCTCGTCTATGGAGCCAACTCGTCTCAGGAAAAATAA
SEQ ID 227:
MSSEKDIKSTCSKFSLSVVAAILASVSGLASCVDLHAGGQSVNELVYVGPQAVLLLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQS
TLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLGIAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCSSLEQGGAC
AAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFGGGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANGGAIAASGKVLFVANDKKTSF
IENRALSGGAIAASSDIAFQNCAELVFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQGGAIFGKNCQISDNEGPVVFRDSTACLGGG
AIAAQEIVSIQNNQAGISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTLCTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIV
KTFASNGKILGGGAILATGKVEITNNSEGISFTGNARAPQALPTQEEFPLFSKKEGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATLLG
CCGGGAVHGMDSTSIVGNSSVRFGNNYAMGQGVSGGALLSKTVQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDNRGRVYGGAISCLRGD
VVISGNKGRVEFKDNIATRLYVEETVEKVEEVEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPESSISSEELAKRRECAGGAIFAKRVRIV
DNQEAVVFSNNFSDIYGGAIFTGSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGAICTQNLTISQNTGNVLFYNNVACSGGAVEIEDH
GNVLLEAFGGDIVFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFENLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQG
SLELLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGHAISKPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQQEGTVE
APQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNEAKVPLMSFVASGDEASAEISNLSVSDLQIHVVTPEIEEDTYGHMGDWSEAKIQDGTLVISWN
PTGYRLDPQKAGALVFNALWEEGAVLSALKNARFAHNLTAQRMEFDYSTNVWGFAFGGFRTLSAENLVAIDGYKGAYGGASAGVDIQLMEDFVLGVSGAA
FLGKMDSQKFDAEVSRKGVVGSVYTGFLAGSWFFKGQYSLGETQNDMKTRYGVLGESSASWTSRGVLADALVEYRSLVGPVRPTFYALHFNPYVEVSYAS
MKFPGFTEQGREARSFEDASLTNITIPLGMKFELAFIKGQFSEVNSLGISYAWEAYRKVEGGAVQLLEAGFDWEGAPMDLPRQELRVALENNTEWSSYFS
TVLGLTAFCGGFTSTDSKLGYEANTGLRLIF
SEQ ID 228:
ATGAGTTCCGAGAAAGATATAAAAAGCACCTGTTCTAAGTTTTCTTTGTCTGTAGTAGCAGCTATCCTTGCCTCTGTTAGCGGGTTAGCTAGTTGCGTAG
ATCTTCATGCTGGAGGACAGTCTGTAAATGAGCTGGTATATGTAGGCCCTCAAGCGGTTTTATTGTTAGACCAAATTCGAGATCTATTCGTTGGGTCTAA
AGATAGTCAGGCTGAAGGACAGTATAGGTTAATTGTAGGAGATCCAAGTTCTTTCCAAGAGAAAGATGCGGATACTCTTCCCGGGAAGGTAGAGCAAAGT
ACTTTGTTCTCAGTAACCAATCCCGTGGTTTTCCAAGGTGTGGACCAACAGGATCAAGTCTCTTCCCAAGGGTTAATTTGTAGTTTTACGAGCAGCAACC
TTGATTCTCCTCGTGACGGAGAATCTTTTTTAGGTATTGCTTTTGTTGGGGATAGTAGTAAGGCTGGAATCACATTAACTGACGTGAAAGCTTCTTTGTC
TGGAGCGGCTTTATATTCTACAGAAGATCTTATCTTTGAAAAGATTAAGGGTGGATTGGAATTTGCATCATGTTCTTCTCTAGAACAGGGGGGAGCTTGT
GCAGCTCAAAGTATTTTGATTCATGATTGTCAAGGATTGCAGGTTAAACACTGTACTACAGCCGTGAATGCTGAGGGGTCTAGTGCGAATGATCATCTTG
GATTTGGAGGAGGCGCTTTCTTTGTTACGGGTTCTCTTTCTGGAGAGAAAAGTCTCTATATGCCTGCAGGAGATATGGTAGTTGCGAATTGTGATGGGGC
TATATCTTTTGAAGGAAACAGCGCGAACTTTGCTAATGGAGGAGCGATTGCTGCCTCTGGGAAAGTGCTTTTTGTCGCTAATGATAAAAAGACTTCTTTT
ATAGAGAACCGAGCTTTGTCTGGAGGAGCGATTGCAGCCTCTTCTGATATTGCCTTTCAAAACTGCGCAGAACTAGTTTTCAAAGGCAATTGTGCAATTG
GAACAGAGGATAAAGGTTCTTTAGGTGGAGGGGCTATATCTTCTCTAGGCACCGTTCTTTTGCAAGGGAATCACGGGATAACTTGTGATAAGAATGAGTC
TGCTTCGCAAGGAGGCGCCATTTTTGGCAAAAATTGTCAGATTTCTGACAACGAGGGGCCAGTGGTTTTCAGAGATAGTACAGCTTGCTTAGGAGGAGGC
GCTATTGCAGCTCAAGAAATTGTTTCTATTCAGAACAATCAGGCTGGGATTTCCTTCGAGGGAGGTAAGGCTAGTTTCGGAGGAGGTATTGCGTGTGGAT
CTTTTTCTTCCGCAGGTGGTGCTTCTGTTTTAGGGACCATTGATATTTCGAAGAATTTAGGCGCGATTTCGTTCTCTCGTACTTTATGTACGACCTCAGA
TTTAGGACAAATGGAGTACCAGGGAGGAGGAGCTCTATTTGGTGAAAATATTTCTCTTTCTGAGAATGCTGGTGTGCTCACCTTTAAAGACAACATTGTG
AAGACTTTTGCTTCGAATGGGAAAATTCTGGGAGGAGGAGCGATTTTAGCTACTGGTAAGGTGGAAATTACTAATAATTCCGAAGGAATTTCTTTTACAG
GAAATGCGAGAGCTCCACAAGCTCTTCCAACTCAAGAGGAGTTTCCTTTATTCAGCAAAAAAGAAGGGCGACCACTCTCTTCAGGATATTCTGGGGGAGG
AGCGATTTTAGGAAGAGAAGTAGCTATTCTCCACAACGCTGCAGTAGTATTTGAGCAAAATCGTTTGCAGTGCAGCGAAGAAGAAGCGACATTATTAGGT
TGTTGTGGAGGAGGCGCTGTTCATGGGATGGATAGCACTTCGATTGTTGGCAACTCTTCAGTAAGATTTGGTAATAATTACGCAATGGGACAAGGAGTCT
CAGGAGGAGCTCTTTTATCTAAAACAGTGCAGTTAGCTGGGAATGGAAGCGTCGATTTTTCTCGAAATATTGCTAGTTTGGGAGGAGGAGCTCTTCAAGC
TTCTGAAGGAAATTGTGAGCTAGTTGATAACGGCTATGTGCTATTCAGAGATAATCGAGGGAGGGTTTATGGGGGTGCTATTTCTTGCTTACGTGGAGAT
GTAGTCATTTCTGGAAACAAGGGTAGAGTTGAATTTAAAGACAACATAGCAACACGTCTTTATGTGGAAGAAACTGTAGAAAAGGTTGAAGAGGTAGAGC
CAGCTCCTGAGCAAAAAGACAATAATGAGCTTTCTTTCTTAGGGAGAGCAGAACAGAGTTTTATTACTGCAGCTAATCAAGCTCTTTTCGCATCTGAAGA
TGGGGATTTATCACCTGAGTCATCCATTTCTTCTGAAGAACTTGCGAAAAGAAGAGAGTGTGCTGGAGGAGCTATTTTTGCAAAACGGGTTCGTATTGTA
GATAACCAAGAGGCCGTTGTATTCTCGAATAACTTCTCTGATATTTATGGCGGCGCCATTTTTACAGGTTCTCTTCGAGAAGAGGATAAGTTAGATGGGC
AAATCCCTGAAGTCTTGATCTCAGGCAATGCAGGGGATGTTGTTTTTTCCGGAAATTCCTCGAAGCGTGATGAGCATCTTCCTCATACAGGTGGGGGAGC
CATTTGTACTCAAAATTTGACGATTTCTCAGAATACAGGGAATGTTCTGTTTTATAACAACGTGGCCTGTTCGGGAGGAGCTGTTCGTATAGAGGATCAT
GGTAATGTTCTTTTAGAAGCTTTTGGAGGAGATATTGTTTTTAAAGGAAATTCTTCTTTCAGAGCACAAGGATCCGATGCTATCTATTTTGCAGGTAAAG
AATCGCATATTACAGCCCTGAATGCTACGGAAGGACATGCTATTGTTTTCCACGACGCATTAGTTTTTGAAAATCTAGAAGAAAGGAAATCTGCTGAAGT
ATTGTTAATCAATAGTCGAGAAAATCCAGGTTACACTGGATCTATTCGATTTTTAGAAGCAGAAAGTAAAGTTCCTCAATGTATTCATGTACAACAAGGA
AGCCTTGAGTTGCTAAATGGAGCCACATTATGTAGTTATGGTTTTAAACAAGATGCTGGAGCTAAGTTGGTATTGGCTGCTGGAGCTAAACTGAAGATTT
TAGATTCAGGAACTCCTGTACAACAAGGGCATGCTATCAGTAAACCTGAAGCAGAAATCGAGTCATCTTCTGAACCAGAGGGTGCACATTCTCTTTGGAT
TGCGAAGAATGCTCAAACAACAGTTCCTATGGTTGATATCCATACTATTTCTGTAGATTTAGCCTCCTTCTCTTCTAGTCAACAGGAGGGGACAGTAGAA
GCTCCTCAGGTTATTGTTCCTGGAGGAAGTTATGTTCGATCTGGAGAGCTTAATTTGGAGTTAGTTAACACAACAGGTACTGGTTATGAAAATCATGCTT
TATTGAAGAATGAGGCTAAAGTTCCATTGATGTCTTTCGTTGCTTCTGGTGATGAAGCTTCAGCCGAAATCAGTAACTTGTCGGTTTCTGATTTACAGAT
TCATGTAGTAACTCCAGAGATTGAAGAAGACACATACGGCCATATGGGAGATTGGTCTGAGGCTAAAATTCAAGATGGAACTCTTGTCATTAGTTGGAAT
CCTACTGGATATCGATTAGATCCTCAAAAAGCAGGGGCTTTAGTATTTAATGCATTATGGGAAGAAGGGGCTGTCTTGTCTGCTCTGAAAAATGCACGCT
TTGCTCATAATCTCACTGCTCAGCGTATGGAATTCGATTATTCTACAAATGTGTGGGGATTCGCCTTTGGTGGTTTCCGAACTCTATCTGCAGAGAATCT
GGTTGCTATTGATGGATACAAAGGAGCTTATGGTGGTGCTTCTGCTGGAGTCGATATTCAATTGATGGAAGATTTTGTTCTAGGAGTTAGTGGAGCTGCT
TTCCTAGGTAAAATGGATAGTCAGAAGTTTGATGCGGAGGTTTCTCGGAAGGGAGTTGTTGGTTCTGTATATACAGGATTTTTAGCTGGATCCTGGTTCT
TCAAAGGACAATATAGCCTTGGAGAAACACAGAACGATATGAAAACGCGTTATGGAGTACTAGGAGAGTCGAGTGCTTCTTGGACATCTCGAGGAGTACT
GGCAGATGCTTTAGTTGAATACCGAAGTTTAGTTGGTCCTGTGAGACCTACTTTTTATGCTTTGCATTTCAATCCTTATGTCGAAGTATCTTATGCTTCT
ATGAAATTCCCTGGCTTTACAGAACAAGGAAGAGAAGCGCGTTCTTTTGAAGACGCTTCCCTTACCAATATCACCATTCCTTTAGGGATGAAGTTTGAAT
TGGCGTTCATAAAAGGACAGTTTTCAGAGGTGAACTCTTTGGGAATAAGTTATGCATGGGAAGCTTATCGAAAAGTAGAAGGAGGCGCGGTGCAGCTTTT
AGAAGCTGGGTTTGATTGGGAGGGAGCTCCAATGGATCTTCCTAGACAGGAGCTGCGTGTCGCTCTGGAAAATAATACGGAATGGAGTTCTTACTTCAGC
ACAGTCTTAGGATTAACAGCTTTTTGTGGAGGATTTACTTCTACAGATAGTAAACTAGGATATGAGGCGAATACTGGATTGCGATTGATCTTTTAA
SEQ ID 229:
MMKRLLCVLLSTSVFSSPMLGYSASKKDSKADICLAVSSGDQEVSQEDLLKEVSRGFSRVAAKATPGVVYIENFPKTGNQAIASPGNKRGFQENPFDYFN
DEFFNRFFGLPSHREQQRPQQRDAVRGTGFIVSEDGYVVTNHHVVEDAGKIHVTLHDGQKYTAKIVGLDPKTDLAVIKIQAEKLPFLTFGNSDQLQIGDW
AIAIGNPFGLQATVTVGVISAKGRNQLHIVDFEDFIQTDAAINPGNSGGPLLNINGQVIGVNTAIVSGSGGYIGIGFAIPSLMAKRVIDQLISDGQVTRG
FLGVTLQPIDSELATCYKLEKVYGALVTDVVKGSPAEKAGLRQEDVIVAYNGKEVESLSALRNAISIMMPGTRVVLKIVREGKTIEIPVTVTQIPTEDGV
SALQKMGVRVQNITPEICKKLGLAADTRGILVVAVEAGSPAASAGVAPGQLILAVNRQRVASVEELNQVLKNSKGENVLLMVSQGDVVRFIVLKSDE
SEQ ID 230:
ATGATGAAAAGATTATTATGTGTGTTGCTATCGACATCAGTTTTCTCTTCGCCAATGCTAGGCTATAGTGCGTCAAAGAAAGATTCTAAGGCTGATATTT
GTCTTGCAGTATCCTCAGGAGATCAAGAGGTTTCACAAGAAGATCTGCTCAAAGAAGTATCCCGAGGATTTTCTCGGGTCGCTGCTAAGGCAACGCCTGG
AGTTGTATATATAGAAAATTTTCCTAAAACAGGGAACCAGGCTATTGCTTCTCCAGGAAACAAAAGAGGCTTTCAAGAGAACCCTTTTGATTATTTTAAT
GACGAATTTTTTAATCGATTTTTTGGATTGCCTTCGCATAGAGAGCAGCAGCGTCCGCAGCAGCGTGATGCTGTAAGAGGAACTGGGTTCATTGTTTCTG
AAGATGGTTATGTTGTTACTAACCATCATGTAGTCGAGGATGCAGGAAAAATTCATGTTACTCTCCACGACGGACAAAAATACACAGCTAAGATCGTGGG
GTTAGATCCAAAAACAGATCTTGCTGTGATCAAAATTCAAGCGGAGAAATTACCATTTTTGACTTTTGGGAATTCTGATCAGCTGCAGATAGGTGACTGG
GCTATTGCTATTGGAAATCCTTTTGGATTGCAAGCAACGGTCACTGTCGGGGTCATTAGTGCTAAAGGAAGAAATCAGCTACATATTGTAGATTTCGAAG
ACTTTATTCAAACAGATGCTGCCATTAATCCTGGGAATTCAGGCGGTCCATTGTTAAACATCAATGGTCAAGTTATCGGGGTTAATACTGCCATTGTCAG
TGGTAGCGGGGGATATATTGGAATAGGGTTTGCTATTCCTAGCTTGATGGCTAAACGAGTCATTGATCAATTGATTAGTGATGGGCAGGTAACAAGAGGC
TTTTTGGGAGTTACCTTGCAACCGATAGATTCTGAATTGGCTACTTGTTACAAATTGGAAAAAGTGTACGGAGCTTTGGTGACGGATGTTGTTAAAGGTT
CTCCAGCAGAAAAAGCAGGGCTGCGCCAAGAAGATGTCATTGTGGCTTACAATGGAAAAGAAGTAGAGTCTTTGAGTGCGTTGCGTAATGCCATTTCCCT
AATGATGCCAGGGACTCGTGTTGTTTTAAAAATCGTTCGTGAAGGGAAAACAATCGAGATACCTGTGACGGTTACACAGATCCCAACAGAGGATGGCGTT
TCAGCGTTGCAGAAGATGGGAGTCCGTGTTCAGAACATTACTCCAGAAATTTGTAAGAAACTCGGATTGGCAGCAGATACCCGAGGGATTCTGGTAGTTG
CTGTGGAGGCAGGCTCGCCTGCAGCTTCTGCAGGCGTCGCTCCTGGACAGCTTATCTTAGCGGTGAATAGGCAGCGAGTCGCTTCCGTTGAAGAGTTAAA
TCAGGTTTTGAAAAACTCGAAAGGAGAGAATGTTCTCCTTATGGTTTCTCAAGGAGATGTGGTGCGATTCATCGTCTTGAAATCAGACGAGTAG
SEQ ID 231:
MKKFISYLLIILPLIGLWEFCAQNYPSFGFICPPPSKVLTTGIHSFPVLFQHSCYTAQGILGGFFLALLLAILFSATMLLFPSTQGLLHPLCVLVQCLPM
FTLAPLIVLWFGWGTRAVIIPTALSIFFPLALTIHQGIKNSPEELLEQFTLYQATTWQKLFKLRIPNGLPHIFSGLKIAMSAAGFATIAGEWVATQSGLG
ILILESRRNYDMAMALAGLFVLTMLTLSLFYSVLLLERSTFFFFRMEKTSKRSFGKKWVFALIPITVLPCLFYLKDDPKLAAPVPTKSFTLLLDWTPNPN
HIPLYAGVEKGFFVDEGISLTLQKNTDTCSSIPHLLLEKVDYTLYHSLGVLKTAVRGAPVQVAGRLIDSSLQGLIYRKNEGIEKLEDLNGRVLGFCLNDS
KNLPNLLEALRKHHVVPSEIKNVSADMISPMLTYQIDFLYGGFYNVEGVTIALKGTPTGCFLSDTYGSPTGPQLLICGKKGSPAMTPQTLQSLQKALSRS
LDFCREYPQEAFAIYVEATKDSPKVLSDERAQWEVTLPLLAKTQEPLSRELLESLLVTLSTTCPDLRTSIDTFSIETLISDVSETIASS
SEQ ID 232:
ATGAAAAAATTTATTAGCTATTTACTCATCATCCTTCCCTTGATTGGACTCTGGGAGTTTTGTGCTCAAAACTATCCGAGTTTTGGCTTTATATGCCCTC
CTCCATCGAAGGTACTTACGACAGGGATCCATTCTTTCCCGGTACTATTCCAGCATTCTTGCTATACAGCCCAAGGCATTTTAGGAGGATTCTTTTTAGC
ATTACTACTTGCTATCCTCTTTTCTGCTACCATGCTTCTATTTCCTTCTACTCAAGGCTTGTTGCACCCCTTGTGTGTTCTGGTGCAATGCCTTCCTATG
TTCACTCTAGCCCCTTTAATCGTTCTTTGGTTTGGTTGGGGGACAAGGGCAGTAATCATCCCAACAGCTCTTAGCATCTTTTTCCCTTTAGCTCTGACCA
TTCATCAGGGAATTAAAAATTCTCCTGAGGAACTCTTAGAACAATTTACGCTTTACCAAGCAACTACTTGGCAGAAACTCTTTAAATTAAGAATTCCTAA
CGGTCTGCCACATATTTTCTCTGGGCTTAAAATTGCTATGAGTGCCGCAGGATTTGCGACCATTGCTGGAGAATGGGTTGCAACACAATCTGGTCTAGGT
ATTCTTATTCTGGAAAGCCGCAGAAACTATGACATGGCAATGGCTCTAGCGGGTTTATTTGTCCTAACCATGCTGACTCTAAGTCTGTTTTATAGCGTTT
TACTTCTTGAGCGCAGCACCTTTTTTTTCTTTAGAATGGAAAAAACTTCCAAAAGATCTTTTGGGAAAAAATGGGTCTTTGCTCTAATTCCAATTACTGT
ATTGCCCTGTCTTTTCTACTTAAAAGACGATCCAAAATTAGCCGCTCCCGTCCCTACTAAATCCTTTACTCTACTCTTGGATTGGACTCCGAATCCTAAT
CACATTCCCCTCTATGCAGGTGTAGAAAAAGGATTTTTTGTAGATGAAGGGATTTCCTTAACCTTACAAAAAAATACGGATACTTGTTCTTCTATTCCTC
ATCTGCTTCTTGAGAAAGTAGATTACACGCTTTACCACAGCTTAGGGGTATTGAAAACTGCAGTTCGAGGAGCTCCTGTTCAAGTAGCAGGCAGACTTAT
CGACAGCTCCTTGCAAGGTCTGATCTATAGAAAAAATGAAGGCATTGAAAAACTTGAAGATCTTAACGGACGCGTACTAGGCTTTTGCCTCAATGACTCC
AAGAACCTGCCTAATCTGCTAGAGGCTTTACGCAAGCATCATGTGGTTCCTTCAGAAATCAAAAACGTCAGCGCAGATATGATTTCTCCTATGCTCACTT
ATCAAATTGATTTCTTGTATGGAGGTTTTTACAATGTTGAGGGCGTCACTATCGCCTTAAAGGGAACCCCTACCGGTTGTTTTCTTTCTGACACTTATGG
ATCCCCTACAGGCCCGCAGCTCCTTATTTGCGGGAAAAAAGGGTCTCCAGCGATGACACCTCAAACACTCCAAAGCTTGCAAAAAGCTTTATCTCGCAGT
CTGGATTTCTGTCGTGAATATCCCCAAGAGGCTTTCGCTATCTACGTAGAAGCAACTAAAGACTCTCCTAAAGTGTTATCCGATGAGCGGGCTCAATGGG
AAGTTACCCTTCCTTTGTTGGCCAAAACTCAGGAACCTTTATCACGAGAATTGCTAGAATCTCTACTCGTAACATTGTCTACAACTTGCCCTGATCTGCG
AACTTCCATCGATACTTTTTCTATTGAAACCTTGATTAGTGATGTATCTGAGACAATAGCTTCTTCCTAA
SEQ ID 233:
MKMNRIWLLLLTFSSAIHSPVQGESLVCKNALQDLSFLEHLLQVKYAPKTWKEQYLGWDLVQSSVSAQQKLRTQENPSTSFCQQVLADFIGGLNDFHAGV
TFFAIESAYLPYTVQKSSDGRFYFVDIMTFSSEIRVGDELLEVDGAPVQDVLATLYGSNHKGTAAEESAALRTLFSRMASLGHKVPSGRTTLKIRRPFGT
TREVRVKWRYVPEGVGDLATIAPSIRAPQLQKSMRSFFPKKDDAFHRSSSLFYSPMVPHFWAELRNHYATSGLKSGYNIGSTDGFLPVIGPVIWESEGLF
RAYISSVTDGDGKSHKVGFLRIPTYSWQDMEDFDPSGPPPWEEFAKIIQVFSSNTEALIIDQTNNPGGSVLYLYALLSMLTDRPLELPKHRMILTQDEVV
DALDWLTLLENVDTNVESRLALGDNMEGYTVDLQVAEYLKSFGRQVLNCWSKGDIELSTPIPLFGFEKIHPHPRVQYSKPICVLINEQDFSCADFFPVVL
KDNDRALIVGTRTAGAGGFVFNVQFPNRTGIKTCSLTGSLAVREHGAFIENIGVEPHIDLPFTANDIRYKGYSEYLDKVKKLVCQLINNDGTIIIAEDGS
F
SEQ ID 234:
ATGAAAATGAATAGGATTTGGCTATTACTGCTTACCTTTTCTTCTGCCATACATTCTCCTGTACAAGGAGAAAGCTTGGTTTGCAAGAATGCTCTTCAAG
ATTTGAGTTTTTTAGAGCATTTATTACAGGTTAAATATGCTCCTAAAACATGGAAAGAGCAATACTTAGGATGGGATCTTGTTCAAAGCTCCGTTTCTGC
ACAGCAGAAGCTTCGTACACAAGAAAATCCATCAACAAGTTTTTGCCAGCAGGTCCTTGCTGATTTTATCGGAGGATTAAATGACTTTCACGCTGGAGTA
ACTTTCTTTGCGATAGAAAGTGCTTACCTTCCTTATACCGTACAAAAAAGTAGTGACGGCCGTTTCTACTTTGTAGATATCATGACTTTTTCTTCAGAGA
TCCGTGTTGGAGATGAGTTGCTAGAGGTGGATGGGGCGCCTGTCCAAGATGTACTCGCTACTCTATATGGAAGCAATCACAAAGGGACTGCAGCTGAAGA
GTCGGCTGCTTTAAGAACACTATTTTCTCGCATGGCCTCTTTAGGGCACAAAGTACCTTCTGGGCGCACTACTTTAAAGATTCGTCGTCCTTTTGGTACT
ACGAGAGAAGTTCGTGTGAAATGGCGTTATGTTCCTGAAGGTGTAGGAGATTTGGCTACCATAGCTCCTTCTATCAGGGCTCCACAGTTACAGAAATCGA
TGAGAAGCTTTTTCCCTAAGAAAGATGATGCGTTTCATCGGTCTAGTTCGCTATTCTACTCTCCAATGGTTCCGCATTTTTGGGCAGAGCTTCGCAATCA
TTATGCAACGAGTGGTTTGAAAAGCGGGTACAATATTGGGAGTACCGATGGGTTTCTCCCTGTCATTGGGCCTGTTATATGGGAGTCGGAGGGTCTTTTC
CGCGCTTATATTTCTTCGGTGACTGATGGGGATGGTAAGAGCCATAAAGTAGGATTTCTAAGAATTCCTACATATAGTTGGCAGGACATGGAAGATTTTG
ATCCTTCAGGACCGCCTCCTTGGGAAGAATTTGCTAAGATTATTCAAGTATTTTCTTCTAATACAGAAGCTTTGATTATCGACCAAACGAACAACCCAGG
TGGTAGTGTCCTTTATCTTTATGCACTGCTTTCCATGTTGACAGACCGTCCTTTAGAACTTCCTAAACATAGAATGATTCTGACTCAGGATGAAGTGGTT
GATGCTTTAGATTGGTTAACCCTGTTGGAAAACGTAGACACAAACGTGGAGTCTCGCCTTGCTCTGGGAGACAACATGGAAGGATATACTGTGGATCTAC
AGGTTGCCGAGTATTTAAAAAGCTTTGGACGTCAAGTATTGAATTGTTGGAGTAAAGGGGATATCGAGTTATCAACGCCTATTCCTCTTTTTGGTTTTGA
GAAGATTCATCCACATCCTCGAGTTCAATACTCTAAACCGATTTGTGTTTTGATCAATGAGCAAGACTTTTCTTGTGCTGACTTCTTCCCTGTAGTTTTG
AAAGACAATGATCGAGCTCTTATTGTTGGTACTCGAACAGCTGGAGCTGGAGGATTTGTCTTTAATGTGCAGTTCCCAAATAGAACTGGAATAAAAACTT
GTTCTTTAACAGGATCATTAGCTGTTAGAGAGCATGGTGCCTTCATTGAGAACATCGGAGTCGAACCGCATATCGATCTGCCTTTTACAGCGAATGATAT
TCGCTATAAAGGCTATTCCGAGTATCTTGATAAGGTCAAAAAATTGGTTTGTCAGCTGATCAATAACGACGGTACCATTATTCTTGCGGAAGATGGTAGT
TTTTAA
SEQ ID 235:
MDTPTPLSSVPTNASLKGEPGSSSQFSSAEKGVLKTSVGDVVLSQSIEDGGNETQISLVGVVNINMAQEELPTLVSPRTFIFLPPETVELEIQIAEMFQA
LEETPSSDSRSLQQKETSAQTPPAPSGKVSIFSLQAQGSSQTRSLPSSQESLSPQQPARAIQGLNTPFSPAARCTIRAVPLSIVPHRRANPTSSQSVSHH
SSRTYQTGHSTGTAQLSSQEWEFSSQTVKTCSTGREKRDGQQERHSDQEQNSDHSYQEEDLSDDMQVSSSKRSSHPEDENTEEVFSVSHFAYHAAPHPSS
NLDQESNQSTFQKRPPSPMSLFSSQNATEEAPKEARVENVFLRFMRLMARILGQAEAEAHELYLRVKERTDNVDALTLLLSKINNEKGAIDWNQDEEMRA
LVDQAKKLGVPIGDSYDWSEEGKKLLKENIQNRKENMEKITQLERTDMQRHLQEVSQCHQARSNVLKLLKELMDTFIYNMRP
SEQ ID 236:
ATGGATACTCCCACACCCCTTTCCTCCGTACCGACAAACGCTTCTCTTAAGGGAGAACCAGGGAGCTCCTCTCAATTTTCTTCTGCAGAAAAAGGGGTTC
TAAAAACAAGCGTAGGAGACGTTGTTCTGTCTCAATCTATTGAAGACGGTGGTAATGAGACTCAGATCTCTCTGGTAGGTGTTGTGAATATTAATATGGC
TCAAGAAGAACTCCCCACTCTTGTTAGCCCTCGAACCTTCATTTTCCTTCCTCCCGAGACTGTCGAGCTGGAAATTCAGATTGCAGAAATGTTCCAAGCT
CTAGAAGAGACCCCTTCTTCTGATAGTCGATCCCTCCAACAGAAGGAAACCTCTGCTCAGACACCTCCAGCACCTTCTGGGAAAGTTTCCATATTTTCTT
TACAGGCGCAGGGATCCTCACAGACTCGCTCCTTACCTTCTTCTCAGGAGTCCCTATCTCCCCAACAACCAGCTCGTGCTATACAGGGACTGAATACTCC
CTTCTCTCCAGCAGCGCGCTGCACAATAAGAGCCGTTCCTTTGTCTATCGTGCCTCACCGTAGAGCAAATCCAACATCTTCTCAAAGTGTTTCTCATCAT
AGCTCTCGTACTTACCAGACAGGCCATTCAACAGGAACGGCTCAACTTTCTTCCCAGGAATGGGAATTTTCTTCTCAAACAGTTAAAACCTGCTCAACAG
GAAGAGAAAAAAGAGACGGTCAACAAGAAAGACATTCTGATCAAGAACAGAATAGTGATCATTCTTACCAAGAGGAAGATCTCTCGGATGATATGCAAGT
GTCTTCTTCTAAAAGATCCTCTCATCCGGAAGATGAAAATACTGAGGAAGTATTTTCTGTCTCTCACTTTGCTTATCATGCGGCCCCTCATCCTTCGTCC
AATTTAGATCAGGAGTCGAATCAGAGTACTTTCCAAAAAAGACCGCCCTCCCCTATGTCCTTGTTTTCTTCCCAGAATGCTACGGAAGAAGCTCCTAAAG
AAGCTCGTGTCGAAAACGTTTTCTTACGATTCATGCGACTCATGGCTAGAATTTTAGGCCAAGCAGAAGCCGAGGCACACGAGTTGTATCTCCGCGTCAA
AGAACGCACAGATAATGTCGATGCGCTGACGTTACTCCTGTCAAAAATTAACAATGAAAAAGGAGCCATTGACTGGAATCAAGATGAGGAAATGCGCGCT
CTCGTAGATCAAGCTAAAAAACTAGGCGTCCCAATTGGAGACTCCTACGACTGGTCTGAGGAAGGAAAAAAGCTTCTGAAAGAAAATATCCAAATGCGCA
AAGAAAATATGGAGAAAATCACTCAGCTAGAACGCACTGATATGCAACGCCATCTCCAAGAAGTGTCTCAATGCCACCAAGCAAGATCCAATGTCTTGAA
ACTTTTAAAAGAACTTATGGACACCTTTATCTACAACATGCGTCCCTAA
SEQ ID 237:
MRLCFILFLLLSPLISEASQHIITVKTIHEIASDILYDDANYWLIFDIDDVLFEGAEALSHSAWFERSIQGMRALGTSEQEAWDTLYPDWLSIQRQGSIK
QIETAIPLLITKVQNQNKIVFAYSERKVCAQDVTLEQLAKINLSFEKANLPYTSLPSNICFTKGVLFGSEIHKGPGLQRFLDAQPSLPEKVIYIDNEKYN
VLRIGEVCKQKNIPYLGIVYTASKYHPPIYLPDIARIQYLYRQKLISNEAAALLSRHRLDK
SEQ ID 238:
ATGCGTCTTTGTTTTATTCTTTTTCTATTGCTATCTCCTTTAATCTCCGAAGCTTCGCAGCACATTATTACTGTGAAAACTATTCATGAGATTGCTTCGG
ACATCTTGTATGATGATGCAAATTACTGGCTGATCTTTGATATCGATGACGTTTTGTTTGAGGGAGCTGAAGCTCTCAGCCATTCAGCTTGGTTTGAACG
CTCCATACAAGGAATGCGGGCATTAGGAACATCCGAGCAAGAAGCTTGGGACACTCTATATCCTGATTGGCTATCTATTCAACGTCAAGGCTCTATTAAA
CAGATAGAAACTGCTATTCCTCTATTAATTACCAAAGTTCAGAATCAAAACAAAATCGTCTTTGCCTATTCAGAGCGCAAAGTATGCGCGCAAGATGTGA
CATTAGAACAACTTGCTAAGATTAACCTCTCTTTTGAGAAAGCGAATCTTCCCTATACCAGTCTCCCATCAAACATCTGTTTCACAAAAGGCGTTCTTTT
TGGATCTGAAATTCATAAAGGACCTGGATTACAACGTTTCCTAGACGCCCAACCCTCTTTACCAGAGAAAGTCATCTACATTGACAATGAGAAATACAAT
GTCTTACGTATTGGAGAAGTCTGTAAACAAAAAAACATCCCTTATCTAGGGATTGTCTATACTGCCTCTAAATATCATCCCCCAATTTATCTTCCAGATA
TTGCCAGAATACAATACCTATACCGCCAAAAGCTCATTAGCAACGAAGCCGCAGCACTCTTATCTCGTCACAGGCTAGATAAGTAA
SEQ ID 239:
MRLCFILFLLLSPLISEASQHIITVKTIHEIASDILYDDANYWLIFDIDDVLFEGAEALSHSAWFERSIQGMRALGTSEQEAWDTLYPDWLSIQRQGSIK
QIETAIPLLITKVQNQNKIVFAYSERKVCAQDVTLEQLAKINLSFEKANLPYTSLPSNICFTKGVLFGSEIHKGPGLQRFLDAQPSLPEKVIYIDNEKYN
VLRIGEVCKQKNIPYLGIVYTASKYHPPIYLPDIARIQYLYRQKLISNEAAALLSRHRLDK
SEQ ID 240:
ATGCGTCTTTGTTTTATTCTTTTTCTATTGCTATCTCCTTTAATCTCCGAAGCTTCGCAGCACATTATTACTGTGAAAACTATTCATGAGATTGCTTCGG
ACATCTTGTATGATGATGCAAATTACTGGCTGATCTTTGATATCGATGACGTTTTGTTTGAGGGAGCTGAAGCTCTCAGCCATTCAGCTTGGTTTGAACG
CTCCATACAAGGAATGCGGGCATTAGGAACATCCGAGCAAGAAGCTTGGGACACTCTATATCCTGATTGGCTATCTATTCAACGTCAAGGCTCTATTAAA
CAGATAGAAACTGCTATTCCTCTATTAATTACCAAAGTTCAGAATCAAAACAAAATCGTCTTTGCCTATTCAGAGCGCAAAGTATGCGCGCAAGATGTGA
CATTAGAACAACTTGCTAAGATTAACCTCTCTTTTGAGAAAGCGAATCTTCCCTATACCAGTCTCCCATCAAACATCTGTTTCACAAAAGGCGTTCTTTT
TGGATCTGAAATTCATAAAGGACCTGGATTACAACGTTTCCTAGACGCCCAACCCTCTTTACCAGAGAAAGTCATCTACATTGACAATGAGAAATACAAT
GTCTTACGTATTGGAGAAGTCTGTAAACAAAAAAACATCCCTTATCTAGGGATTGTCTATACTGCCTCTAAATATCATCCCCCAATTTATCTTCCAGATA
TTGCCAGAATACAATACCTATACCGCCAAAAGCTCATTAGCAACGAAGCCGCAGCACTCTTATCTCGTCACAGGCTAGATAAGTAA
SEQ ID 241:
MRLCFILFLLLSPLISEASQHIITVKTIHEIASDILYDDANYWLIFDIDDVLFEGAEALSHSAWFERSIQGMRALGTSEQEAWDTLYPDWLSIQRQGSIK
QIETAIPLLITKVQNQNKIVFAYSERKVCAQDVTLEQLAKINLSFEKANLPYTSLPSNICFTKGVLFGSEIHKGPGLQRFLDAQPSLPEKVIYIDNEKYN
VLRIGEVCKQKNIPYLGIVYTASKYHPPIYLPDIARIQYLYRQKLISNEAAALLSRHRLDK
SEQ ID 242:
ATGCGTCTTTGTTTTATTCTTTTTCTATTGCTATCTCCTTTAATCTCCGAAGCTTCGCAGCACATTATTACTGTGAAAACTATTCATGAGATTGCTTCGG
ACATCTTGTATGATGATGCAAATTACTGGCTGATCTTTGATATCGATGACGTTTTGTTTGAGGGAGCTGAAGCTCTCAGCCATTCAGCTTGGTTTGAACG
CTCCATACAAGGAATGCGGGCATTAGGAACATCCGAGCAAGAAGCTTGGGACACTCTATATCCTGATTGGCTATCTATTCAACGTCAAGGCTCTATTAAA
CAGATAGAAACTGCTATTCCTCTATTAATTACCAAAGTTCAGAATCAAAACAAAATCGTCTTTGCCTATTCAGAGCGCAAAGTATGCGCGCAAGATGTGA
CATTAGAACAACTTGCTAAGATTAACCTCTCTTTTGAGAAAGCGAATCTTCCCTATACCAGTCTCCCATCAAACATCTGTTTCACAAAAGGCGTTCTTTT
TGGATCTGAAATTCATAAAGGACCTGGATTACAACGTTTCCTAGACGCCCAACCCTCTTTACCAGAGAAAGTCATCTACATTGACAATGAGAAATACAAT
GTCTTACGTATTGGAGAAGTCTGTAAACAAAAAAACATCCCTTATCTAGGGATTGTCTATACTGCCTCTAAATATCATCCCCCAATTTATCTTCCAGATA
TTGCCAGAATACAATACCTATACCGCCAAAAGCTCATTAGCAACGAAGCCGCAGCACTCTTATCTCGTCACAGGCTAGATAAGTAA
SEQ ID 243:
MCFIGIGSLLLPTALRATERMRKEPIPLLDKQQSFWNVDPYCLESICACFVAHRDPLSAKQLMYLFPQLSEEDVSVFARCILSSKRPEYLFSKSEEELFA
KLILPRVSLGVHRDDDLARVLVLAEPSAEEQKARYYSLYLDVLALRAYVERERLASAAHGDPERIDLATIEAINTILFQEEGWRYPSKQEMFENRFSELA
AVTDSKFGVCLGTVVLYQAVAQRLDLSLDPVTPPGHIYLRYKDKVNIETTSGGRHLPTERYCECIKESQLKVRSQMELIGLTFMNRGAFFLQKGEFLQAS
LAYEQAQSYLSDEQISDLLGITYVLLGKKAAGEALLKKSAEKTRRGSSIYDYFQGYISPEILGVLFADSGVTYQETLEYRKKLVMLSKKYPKSGSLRLRL
ATTALELGLVKEGVQLLEESVKDAPEDLSLRLQFCKILCNRHDYVRAKYHFDQAQALLIKEGLFSEKTSYTLLKTIGKKLSLFAPS
SEQ ID 244:
ATGTGCTTTATTGGGATAGGCAGTCTTCTGTTACCGACCGCTCTGCGAGCGACTGAACGGATGAGAAAGGAGCCTATCCCGCTCCTAGATAAGCAACAAA
GCTTTTGGAATGTAGATCCTTATTGTCTGGAATCTATATGCGCTTGTTTTGTAGCGCATCGAGATCCTTTGAGTGCAAAACAGTTAATGTATCTGTTTCC
TCAGCTCTCAGAAGAGGATGTATCTGTTTTTGCTCGATGCATTTTGTCTTCAAAGCGTCCAGAATACCTCTTTTCAAAATCGGAGGAAGAGCTCTTTGCA
AAATTGATTTTGCCAAGGGTTTCTCTAGGTGTTCATCGGGACGATGATTTAGCGAGAGTGTTGGTGTTAGCGGAGCCTTCTGCAGAAGAGCAGAAGGCTC
GATACTATTCATTGTATCTGGATGTTTTAGCTTTGCGTGCATACGTTGAAAGAGAGCGTTTGGCGAGTGCTGCACACGGAGATCCTGAGCGGATAGATTT
GGCAACCATAGAAGCTATTAATACCATCCTTTTTCAGGAAGAAGGATGGAGGTATCCTTCAAAACAAGAGATGTTTGAAAACAGGTTTTCTGAGTTAGCT
GCTGTTACAGATAGTAAGTTTGGAGTTTGCTTGGGAACTGTAGTGCTTTATCAAGCTGTCGCCCAGCGGCTTGATTTGTCTCTGGACCCTGTCACCCCTC
CTGGACATATTTACTTACGCTATAAGGACAAGGTGAATATTGAAACCACTTCTGGAGGAAGGCATCTTCCTACTGAAAGGTATTGTGAATGCATAAAAGA
GTCGCAGTTAAAGGTGCGTTCGCAGATGGAGCTTATAGGGTTAACTTTTATGAATAGAGGAGCTTTCTTTTTGCAAAAAGGAGAGTTTCTTCAGGCGTCC
TTAGCTTATGAGCAAGCTCAATCATATTTATCAGACGAGCAGATTTCTGATTTGTTAGGGATTACTTATGTTCTTTTAGGAAAGAAGGCGGCGGGAGAGG
CTCTTTTAAAGAAATCTGCAGAAAAGACTCGGCGAGGGTCATCTATCTATGACTATTTCCAAGGATATATTTCCCCCGAAATCCTAGGGGTGTTGTTTGC
CGATTCAGGGGTGACCTATCAAGAAACTTTGGAGTATCGAAAAAAACTAGTGATGCTTTCCAAGAAGTATCCAAAAAGTGGATCTCTTAGGTTGAGGTTG
GCGACAACAGCATTGGAGCTAGGGCTGGTCAAGGAGGGGGTGCAGTTGTTAGAAGAGAGTGTTAAGGATGCCCCAGAGGACCTCTCTTTACGTCTGCAGT
TTTGTAAAATTCTTTGCAATCGACATGATTATGTCCGAGCAAAATATCATTTTGATCAAGCGCAAGCTCTTCTCATTAAAGAAGGGTTGTTTTCCGAAAA
AACTTCCTATACTCTCTTAAAAACTATCGGGAAAAAGCTATCTCTTTTTGCTCCGAGTTAA
SEQ ID 245:
MLSKFCKLSLSAILLINTLAPSETFSEEGTSGFLGRMKSWILKDKTILSTTEESQTSAIEKVSDLLSWKRYDYTQESGFAIQFPESPEHSEQVIEVPQSD
LAIRYDTYVAETPSDSTVVVVSIWEYPEKIDISRPELNLQEGFAGMLYALPESQVLYLKATALQGHKALEFWIACDDVYFRGMLVSVNHTLYQVFMVYKG
RSPEILDKEYSTFIQSFKVTKVRNSKKMDIRKRVSL
SEQ ID 246:
ATGCTTTCAAAGTTCTGCAAACTTTCTTTATCTGCTATCCTTTTAATTAATACTTTGGCTCCTTCAGAAACTTTTTCTGAAGAAGGAACCTCAGGGTTTT
TAGGGAGGATGAAGTCCTGGATCTTAAAGGACAAGACTATTCTCTCTACCACAGAGGAATCTCAAACCTCTGCTATCGAAAAGGTTTCGGATCTCTTGTC
TTGGAAGCGTTATGATTACACACAGGAAAGCGGTTTTGCTATCCAATTTCCTGAGTCTCCCGAACATTCGGAGCAAGTGATAGAAGTCCCTCAATCAGAT
TTGGCTATTCGTTACGATACCTATGTAGCAGAAACTCCTAGTGATAGCACAGTTTATGTAGTGTCTATTTGGGAATATCCAGAGAAAATTGATATCAGTA
GACCGGAATTGAACCTTCAAGAAGGTTTTGCAGGAATGTTATACGCACTTCCTGAATCGCAAGTTCTATATCTTAAAGCAACAGCTCTACAAGGACACAA
AGCTTTGGAATTTTGGATCGCATGCGACGATGTGTATTTTCGAGGAATGCTTGTCTCTGTTAATCACACGCTGTACCAAGTTTTCATGGTGTATAAGGGA
CGTTCCCCAGAAATTTTAGATAAGGAATACAGCACCTTCATTCAATCTTTCAAAGTCACTAAGGTACGAAACTCCAAAAAAATGGACATAAGAAAGCGTG
TATCTTTATAG
SEQ ID 247:
MASKSRHYLNQPWYIILFIFVLSLIAGTLLSSVYYVLAPIQQQAAEFDRNQQMLMAAQVISSDNTFQVYEKGDWHPALYNTKKQLLEISSTPPKVTVTTL
SSYFQNFVRVLLTDTQGNLSSFEDHNLNLEEFLSQPTPVIHGLALYVVYAILHNDAASSKLSASQVAKNPTAIESIVLPIEGFGLWGPIYGFLALEKDGN
TVLGTSWYQHGETPGLGANIANPQWQKNFRGKKVFLVSASGETDFAKTTLGLEVIKGSVSAALGDSPKAASSIDGISGATLTCNGVTESFSHSLAPYRAL
LTFFANSKPSGESHDH
SEQ ID 248:
ATGGCATCCAAGTCTCGCCATTATCTTAATCAGCCTTGGTACATTATCTTATTCATCTTTGTTCTTAGTTTAATTGCTGGTACCCTCCTGTCTTCTGTGT
ATTATGTCCTTGCACCTATCCAACAGCAAGCTGCGGAATTCGATCGCAATCAACAAATGCTAATGGCTGCACAAGTAATTTCTTCCGATAACACATTCCA
AGTCTATGAAAAGGGAGATTGGCACCCAGCCCTATATAATACTAAAAAGCAGTTGCTAGAGATCTCCTCTACTCCTCCTAAAGTAACCGTGACAACTTTA
AGCTCATATTTTCAAAACTTTGTTAGAGTCTTGCTTACAGATACACAAGGAAATCTTTCTTCATTCGAAGACCATAATCTCAATCTAGAAGAATTTTTAT
CTCAACCAACTCCTGTAATACATGGTCTTGCCCTTTATGTGGTCTACGCTATCCTACACAACGATGCAGCTTCCTCTAAATTATCTGCTTCCCAAGTAGC
GAAAAATCCAACAGCTATAGAATCTATAGTTCTTCCTATAGAAGGTTTTGGTTTGTGGGGACCTATCTATGGATTCCTTGCTCTAGAAAAAGACGGGAAT
ACTGTTCTTGGTACTTCTTGGTATCAACATGGCGAGACTCCTGGATTAGGAGCAAATATCGCTAACCCTCAATGGCAAAAAAATTTCAGAGGCAAAAAAG
TATTTCTAGTCTCAGCTTCTGGAGAAACAGATTTTGCTAAGACAACCCTAGGACTGGAAGTTATAAAAGGATCTGTATCTGCAGCATTAGGAGACTCACC
TAAAGCTGCTTCTTCCATCGACGGAATTTCAGGAGCTACTTTGACTTGTAATGGTGTTACCGAATCCTTCTCTCATTCTCTAGCTCCCTACCGCGCTTTG
TTGACTTTCTTCGCCAACTCTAAACCTAGTGGAGAGTCTCATGACCACTAA
SEQ ID 249:
MMKPLRFGYFFCAIYFTLLQAAFAKEPNSCPDCQNNWKEVTHTDQLPENIIHADDACYHSGYVQALIDMHFLDSCCQVIVENQTAYLFSLPTDDVTRNAI
INLIKDLPFIHSVEICQASYQTCHHQGPHGKTSLPEQRSFCTKVCGKEAIWLPQNTILFSPLVADPRQATNSAGIRFNDEVLGKRVGSATFGGDFIFLRL
FDISRFHGDMDIGLQGAVFSVFDLDHPEACMVNSDFFVAALCNFAVNKWSYRFRLWHLSSHLGDEFILANQLPPKKRYNRSDEAVDFFASFRYTPQIRVY
GGIGYIISRDLTFPEDPLYFEGGIELRPFGLREDNLHAQPVFAMHFRFWEEHDFSIDQTYIVGMEWSKFQDVGRKVRAVLEYHQGFSHEGQFVREECDYY
GFRLSYGF
SEQ ID 250:
ATGATGAAACCTCTACGTTTCGGTTATTTCTTTTGCGCAATCTATTTTACTTTGTTACAGGCAGCGTTTGCTAAAGAACCGAATTCTTGTCCCGACTGCC
AGAATAATTGGAAAGAAGTCACCCACACGGATCAACTCCCAGAAAACATCATTCATGCTGATGATGCTTGTTATCACTCTGGTTATGTACAGGCTCTCAT
TGATATGCATTTCTTAGATAGCTGCTGCCAGGTCATCGTTGAAAACCAAACTGCTTACTTATTTTCTCTTCCTACAGATGATGTTACGCGCAACGCCATT
ATCAACCTAATTAAAGACCTTCCATTCATTCACTCCGTAGAAATCTGCCAAGCATCCTATCAAACCTGTCATCATCAAGGCCCTCATGGAAAGACTTCTC
TTCCAGAACAACGTTCTTTCTGTACAAAGGTCTGTGGAAAAGAAGCTATTTGGTTACCACAGAATACCATCCTATTCTCGCCTCTTGTAGCAGATCCTAG
ACAAGCAACTAATAGTGCAGGTATCCGTTTTAACGACGAAGTCTTAGGAAAACGTGTTGGCTCTGCTACCTTCGGTGGAGATTTCATCTTCTTACGATTA
TTTGATATCTCCCGATTCCATGGAGACATGGATATTGGTCTCCAAGGAGCTGTATTCTCTGTTTTCGACCTGGATCATCCAGAAGCTTGCATGGTCAACT
CTGACTTTTTTGTCGCCGCTTTGTGCAACTTTGCAGTGAACAAATGGAGCTACCGCTTCAGACTATGGCATCTTTCTTCTCATCTTGGCGACGAATTTAT
TCTTGCCAACCAGTTACCTCCTAAAAAACGTTATAATCGAAGCGATGAAGCCGTCGATTTCTTTGCTTCTTTTCGTTACACTCCACAGATCCGTGTTTAT
GGAGGTATTGGGTATATCATTAGTCGAGATTTAACATTCCCTGAAGATCCTCTTTACTTTGAAGGAGGTATCGAACTACGTCCTTTCGGATTACGGGAAG
ACAACCTTCATGCCCAACCCGTCTTTGCTATGCATTTTCGCTTTTGGGAAGAGCATGACTTTTCTATAGACCAAACTTATATAGTAGGCATGGAGTGGTC
CAAATTCCAGGATGTAGGGAGAAAAGTGCGCGCTGTATTGGAATACCACCAAGGTTTCTCCCACGAAGGACAATTTGTCCGAGAAGAATGCGATTATTAT
GGCTTTCGATTAAGTTATGGCTTCTAG
SEQ ID 251:
MLLRKFCGYLFCSSLVCSFISVIVVSFRSEPITPSVAIFSSFSHNSLSECIESCQKELTSFGNMPTISLFNSEDNVVKARKIARTLHKDPNVVMIITLGP
IATKVMSQIETQKPIIYAVVPAGEALRFPKEQVNIYGVNDSVDTNQCCFAIHAVTNNANSLVYLQPHEPFPSSLQEEITNKLRASGIKVTELPISAANMS
SRIQFIAENRPSAVFFPLSSLSEKNGTTLIKSILKENIPLITDDSSLVMEGACAACSVDYKLSGKQIACIVRYLLSKKNNEEHLNQISAEPILSKITFNE
EIIRFLGLPFNVAPAHQFISFHSADNTGLVTLQIP
SEQ ID 252:
ATGCTTTTGCGAAAATTTTGTGGCTATCTTTTTTGTAGTTCCCTAGTTTGTTCTTTTATTTCCGTCATTGTTGTTTCCTTTCGTTCAGAACCAATAACGC
CTAGCGTTGCTATCTTCTCTTCCTTTTCCCATAATTCTCTTAGTGAATGCATAGAGAGTTGTCAAAAAGAACTGACCAGCTTTGGGAACATGCCCACTAT
CTCCCTATTTAATTCTGAGGATAATGTAGTCAAAGCAAGAAAAATCGCTCGCACCCTTCATAAAGACCCTAATGTTGTCATGATCATTACTTTAGGCCCC
ATTGCAACTAAAGTAATGAGTCAAATCGAAACACAAAAACCGATCATTTATGCTGTTGTCCCTGCAGGAGAAGCTCTCCGATTCCCAAAAGAGCAGGTTA
ATATATACGGGGTTAATGATAGCGTAGACACAAACCAATGTTGTTTCGCGATTCATGCGGTAACCAACAACGCGAATTCGTTGGTTTATCTACAACCCCA
CGAACCTTTCCCTTCTTCCTTACAGGAAGAAATTACAAATAAACTCCGCGCGTCAGGCATTAAAGTGACAGAACTTCCTATTTCTGCAGCCAACATGTCG
TCTCGCATTCAGTTTATTGCAGAAAATCGTCCTTCCGCAGTCTTTTTCCCTCTTTCTTCCCTATCAGAAAAAATGGGAACGACGCTCATTAAAAGCATCT
TAAAAGAAAATATTCCTCTGATCACAGATGACTCTTCCCTTGTTATGGAAGGTGCTTGTGCAGCATGTAGCGTTGATTATAAACTATCAGGCAAACAAAT
AGCCTGTATCGTTCGTTATTTGCTCAGCAAGAAAAACAATGAAGAGCATTTGAACCAGATTAGCGCAGAGCCGATCCTTTCCAAAATTACTTTCAATGAG
GAAATTATCCGGTTCTTAGGACTTCCATTTAATGTGGCTCCGGCTCACCAATTTATCTCTTTCCACTCTGCAGATAATACTGGATTAGTGACTTTACAAA
TCCCTTAA
SEQ ID 253:
MTTLLSFLTSLCSAAIHQAFPELEELTLDITPSTKEHFGHYQCNDAMKLARVLHKSPRAIAESIVAHIPPTPFSSIEIAGAGFINFTFSKEFLASQLQTF
SKELANGFRAASPQKVIIDFSSPNIAKDMHVGHLRSTIIGDCLARCFSFVGHDVLRLNHIGDWGTAFGMLITYLQETSQEAIHQLEDLTALYKKAHARFA
EDSEFKKRSQHNVVALQSGDAQALALWKQICSVSEKSFQTIYSILDVELHTRGESFYNPFLAEVVADLESKNLVTLSDGAKCVFHFAFSIPLMIQKSDGG
YNYATTDVAAMRYRIQQDQADRILIVTDSGQSLHFQLLEATCLAAGYLPSKGIFSHVGFGLVLDTQGRKFKTRSGENIKLRELLDTAVEKAKESLKAHRP
DISEEELAYQGPILGINAIKYADLSSHRINDYVFSFEKMLRFEGNTAMSLLYAYVRIQGIKRRMGLESPPQEGPLAVHEPAEFALALTLLRFPEILDLTL
RELCPHFLTDYLYALTNKFNAFFRDCHIEGSDSQQERLYLCGLTERTLSTGMHLLGLKTLNHL
SEQ ID 254:
ATGACAACACTTCTTTCTTTTCTGACTTCGCTATGTTCTGCAGCGATTCATCAAGCCTTCCCTGAGTTGGAAGAGCTAACCTTAGACATCACTCCCTCTA
CTAAGGAGCATTTTGGACATTATCAATGTAACGATGCAATGAAACTTGCACGTGTATTACACAAATCCCCTCGTGCCATTGCCGAATCGATCGTTGCGCA
TATTCCTCCCACTCCTTTTTCCTCTATAGAGATTGCAGGAGCTGGATTTATCAATTTTACTTTCTCAAAAGAATTCCTAGCTAGTCAGCTCCAAACCTTC
TCAAAAGAATTAGCAAATGGGTTTCGTGCTGCGTCTCCTCAAAAAGTTATTATTGATTTTTCTTCTCCTAATATTGCTAAAGATATGCATGTAGGCCATC
TGCGCTCCACGATTATCGGAGATTGTTTAGCACGATGCTTTTCCTTTGTCGGCCATGACGTCTTACGCTTAAACCATATTGGAGATTGGGGTACAGCTTT
TGGTATGCTAATCACCTATCTGCAAGAGACCTCTCAGGAGGCGATTCATCAACTAGAAGATCTCACTGCATTATATAAAAAGGCTCACGCGCGTTTCGCA
GAAGACTCTGAATTTAAAAAACGCTCCCAACATAACGTTGTAGCCTTACAATCCGGAGATGCTCAAGCTCTTGCACTATGGAAACAAATCTGTTCCGTTT
CTGAGAAATCCTTTCAGACAATCTACTCGATTTTGGATGTTGAGCTCCATACACGCGGCGAATCATTTTATAATCCTTTCCTAGCAGAGGTTGTCGCAGA
CTTAGAATCTAAAAACCTTGTCACGCTTTCTGATGGCGCAAAATGCGTATTCCATGAAGCCTTCTCTATTCCTCTCATGATTCAAAAGAGTGATGGCGGA
TACAATTACGCAACAACCGATGTCGCAGCTATGCGCTATCGCATCCAACAAGATCAGGCCGATAGAATTCTTATCGTTACAGACTCAGGACAATCCTTAC
ACTTCCAGCTTCTAGAAGCAACGTGCTTAGCAGCAGGCTATCTTCCTTCTAAAGGGATCTTTTCACATGTAGGATTTGGACTTGTCTTGGATACTCAAGG
AAGAAAATTCAAAACACGTTCGGGAGAGAACATCAAATTACGAGAACTTCTCGATACAGCAGTGGAAAAAGCGAAAGAGTCTCTAAAAGCACATCGTCCA
GACATCTCAGAAGAAGAACTGGCATATCAAGGCCCTATCCTTGGTATTAATGCAATTAAATATGCAGACCTTTCTTCTCATAGAATCAATGACTACGTGT
TCTCTTTCGAGAAGATGCTCCGCTTCGAAGGAAATACAGCGATGTCTCTCCTGTATGCCTATGTACGTATCCAAGGAATTAAACGCAGAATGGGATTAGA
ATCTCCGCCTCAAGAAGGGCCTCTTGCTGTTCATGAGCCTGCAGAAGAAGCGTTAGCACTTACTCTTTTACGTTTCCCTGAAATTTTGGACCTCACCCTC
AGAGAACTCTGTCCTCATTTCCTAACTGACTATCTCTATGCACTCACCAATAAGTTCAATGCTTTCTTCCGCGATTGCCATATCGAAGGATCCGATTCTC
AGCAAGAACGTCTTTATCTCTGCGGACTTACCGAACGAACGCTATCAACAGGTATGCACTTACTAGGTCTTAAAACCTTGAATCACCTGTAA
SEQ ID 255:
MTNSISGYQPTVTTSTSSTTSASGASGSLGASSVSTTANATVTQTANATNSAATSSIQTTGETVVNYTNSASAPNVTVSTSSSSTQATATSNKTSQAVAG
KITSPDTSESSETSSTSSSDHIPSDYDDVGSNSGDISNNYDDVGSNNGDISSNYDDAAADYEPIRTTENIYESIGGSRTSGPENTSGGAAAALNSLRGSS
YSNYDDAAADYEPIRTTENIYESIGGSRTSGPENTSGGAAAALNSLRGSSYSNYDDAAADYEPIRTTENIYESIGGSRTSGPENTSDGAAAAALNSLRGS
SYTTGPRNEGVFGPGPEGLPDMSLPSYDPTNKTSLLTFLSNPHVKSKMLENSGHFVFIDTDRSSFILVPNGNWDQVCSIKVQNGKTKEDLDIKDLENMCA
KFCTGFSKFSGDWDSLVEPMVSAKAGVASGGNLPNTVIINNKFKTCVAYGPWNSQEASSGYTPSAWRRGHRVDFGGIFEKANDFNKINWGTQAGPSSEDD
GISFSNETPGAGPAAAPSPTPSSIPIINVNVNVGGTNVNIGDTNVNTTNTTPTTQSTDASTDTSDIDDINTNNQTDDINTTDKDSDGAGGVNGDISETES
SSGDDSGSVSSSESDKNASVGNDGPAMKDILSAVRKHLDVVYPGENGGSTEGPLPANQTLGDVISDVENKGSAQDTKLSGNTGAGDDDPTTTAAVGNGAE
EITLSDTDSGIGDDVSDTASSSGDESGGVSSPSSESNKNTAVGNDGPSGLDILAAVRKHLDKVYPGDNGGSTEGPLQANQTLGDIVQDMETTGTSQETVV
SPWKGSTSSTESAGGSGSVQTLLPSPPPTPSTTTLRTGTGATTTSLMMGGPIKADIITTGGGGRIPGGGTLEKLLPRIRAHLDISFDAQGDLVSTEEPQL
GSIVNKFRQETGSRGILAFVESAPGKPGSAQVLTGTGGDKGNLFQAAAAVTQALGNVAGKVNLAIQGQKLSSLVNDDGKGSVGRDLFQAAAQTTQVLSAL
IDTVG
SEQ ID 256:
ATGACGAATTCTATATCAGGTTATCAACCTACTGTTACAACTTCTACATCATCAACCACTTCGGCATCAGGTGCTTCCGGATCTCTGGGAGCTTCTTCTG
TATCTACTACCGCAAACGCTACAGTTACACAAACAGCAAACGCAACAAATTCAGCGGCTACATCTTCTATCCAAACGACTGGAGAGACTGTAGTAAACTA
TACGAATTCAGCCTCCGCCCCCAATGTAACTGTATCGACCTCCTCTTCTTCCACACAAGCCACAGCCACTTCGAATAAAACTTCCCAAGCCGTTGCTGGA
AAAATCACTTCTCCAGATACTTCAGAAAGCTCAGAAACTAGCTCTACCTCATCAAGCGATCATATCCCTAGCGATTACGATGACGTTGGTAGCAATAGTG
GAGATATTAGCAACAACTACGATGACGTAGGTAGTAACAACGGAGATATCAGTAGCAATTATGACGATGCTGCTGCTGATTACGAGCCGATAAGAACTAC
TGAAAATATTTATGAGAGTATTGGTGGCTCTAGAACAAGTGGCCCAGAAAATACAAGTGGTGGTGCAGCAGCAGCACTCAATTCTCTAAGAGGCTCCTCC
TACAGCAATTATGACGATGCTGCTGCTGATTACGAGCCGATAAGAACTACTGAAAATATTTATGAGAGTATTGGTGGCTCTAGAACAAGTGGCCCAGAAA
ATACGAGTGGTGGTGCAGCAGCAGCACTCAATTCTCTAAGAGGCTCCTCCTACAGCAATTATGACGATGCTGCTGCTGATTACGAGCCGATAAGAACTAC
TGAAAATATTTATGAGAGTATTGGTGGCTCTAGAACAAGTGGCCCAGAAAATACGAGTGATGGTGCAGCAGCAGCAGCACTCAATTCTCTAAGAGGCTCC
TCCTACACAACAGGGCCTCGTAACGAGGGTGTATTCGGCCCTGGACCGGAAGGACTACCAGACATGTCTCTTCCTTCATACGATCCTACAAATAAAACCT
CGTTATTGACTTTCCTCTCCAACCCTCATGTAAAGTCGAAAATGCTTGAAAACTCGGGGCATTTCGTCTTCATTGATACAGATAGAAGTAGTTTCATTCT
TGTTCCTAACGGAAATTGGGACCAAGTCTGTTCAATTAAAGTTCAAAATGGAAAGACCAAAGAAGATCTCGACATCAAAGACTTGGAAAACATGTGTGCA
AAATTCTGTACAGGGTTTAGCAAATTCTCTGGTGACTGGGACAGTCTTGTAGAACCTATGGTGTCAGCCAAAGCTGGAGTGGCCAGCGGAGGCAATCTTC
CCAATACAGTGATTATCAATAATAAATTCAAAACTTGCGTTGCTTATGGTCCTTGGAATAGCCAGGAAGCAAGTTCTGGTTATACACCTTCTGCTTGGAG
ACGTGGTCATCGAGTAGATTTTGGAGGAATTTTTGAGAAAGCCAACGACTTTAATAAAATCAACTGGGGAACTCAAGCCGGGCCTAGTAGCGAAGACGAT
GGCATTTCCTTCTCCAATGAAACTCCTGGAGCTGGTCCTGCAGCTGCTCCATCACCAACGCCATCCTCTATTCCTATCATCAATGTCAATGTCAATGTTG
GCGGAACTAATGTGAATATTGGAGATACGAATGTCAACACGACTAACACCACACCAACAACTCAATCTACAGACGCCTCTACAGATACAAGCGATATCGA
TGACATAAATACCAACAACCAAACTGATGATATCAATACGACAGACAAAGACTCTGACGGAGCTGGTGGAGTCAATGGCGATATATCCGAAACAGAATCC
TCTTCTGGAGATGATTCAGGAAGTGTCTCTTCCTCAGAATCAGACAAGAATGCCTCTGTCGGAAATGACGGACCTGCTATGAAAGATATCCTTTCTGCCG
TGCGTAAACACCTAGACGTCGTTTACCCTGGCGAAAATGGCGGTTCTACAGAAGGGCCTCTCCCAGCTAACCAAACTCTCGGAGACGTAATCTCTGATGT
AGAGAATAAAGGCTCCGCTCAGGATACAAAATTGTCAGGAAATACAGGAGCTGGGGATGACGATCCAACAACCACAGCTGCTGTAGGTAATGGAGCGGAA
GAGATCACTCTTTCCGACACAGATTCTGGTATCGGAGATGATGTATCCGATACAGCGTCTTCATCTGGGGATGAATCCGGAGGAGTCTCCTCTCCCTCTT
CAGAATCCAATAAAAATACTGCCGTTGGAAATGACGGACCTTCTGGACTAGATATCCTCGCTGCCGTACGTAAACATTTAGATAAGGTTTACCCTGGCGA
CAATGGTGGTTCTACAGAAGGGCCTCTCCAAGCTAACCAAACTCTTGGAGATATCGTCCAGGATATGGAAACAACAGGGACATCCCAAGAAACCGTTGTA
TCCCCATGGAAAGGAAGCACTTCTTCAACGGAATCAGCAGGAGGAAGTGGTAGCGTACAAACACTACTGCCTTCACCACCTCCAACCCCGTCAACTACAA
CATTAAGAACGGGCACAGGAGCTACCACCACATCCTTGATGATGGGAGGACCAATCAAAGCTGACATAATAACAACTGGTGGCGGAGGACGAATTCCTGG
AGGAGGAACGTTAGAAAAGCTGCTCCCTCGTATACGTGCGCACTTAGACATATCCTTTGATGCGCAAGGCGATCTCGTAAGTACTGAAGAGCCTCAGCTT
GGCTCGATTGTAAACAAATTCCGCCAAGAAACTGGTTCAAGAGGAATCTTAGCTTTCGTTGAGAGTGCTCCAGGCAAGCCGGGATCTGCACAGGTCTTAA
CGGGTACAGGGGGAGATAAAGGCAACCTATTCCAAGCAGCTGCCGCAGTCACCCAAGCCTTAGGAAATGTTGCAGGGAAAGTCAACCTTGCGATACAAGG
CCAAAAACTATCATCCCTAGTCAATGACGACGGGAAGGGGTCTGTTGGAAGAGATTTATTCCAAGCAGCAGCCCAAACAACTCAAGTGCTAAGCGCACTG
ATTGATACCGTAGGATAA
SEQ ID 257:
MRTFFLLYRFFICLAPFFLSFPLYADPHTVLTKGIAAAVVHADSGAILKEKNLDHKIFPASMTKIATALLILRQYPDVLTRFITTRREPLTSITPQAKQQ
SGYRSPPHWLETDGMTIQLKVKEEVSGWDLFHALLISSANDAANVLADACCQSVSAFMRQLNEFLRELGCQNTHFNSPHGLHHPDHYTTARDLSLIMKEA
LKEPLFRQVIHTASYTMEATNLSPERVLSSTNKLLSSSSTYFYPPCLGGKTGTTKSAGKNIIFAAEKNNRSIIVVAAGYFGPAAQLYQDAIALCEDLFNE
QLLRCFLIPPASHYPVPTRFGTVTAPVAQGIYYDFYPSEEIPS
SEQ ID 258:
ATGCGTACTTTTTTCTTGTTGTATCGGTTCTTTATCTGCTTGGCTCCCTTTTTTCTCTCGTTTCCTTTGTACGCAGATCCCCATACTGTTCTTACAAAAG
GAATCGCAGCCGCAGTCGTTCATGCAGATTCCGGAGCGATTCTGAAAGAAAAAAATCTGGACCACAAGATTTTCCCTGCAAGCATGACCAAGATTGCAAC
CGCTTTACTCATTTTAAGGCAGTATCCTGATGTGTTAACTCGTTTCATCACTACTCGCAGAGAGCCACTGACTTCTATCACTCCTCAGGCTAAACAACAA
TCCGGATACCGAAGCCCTCCCCATTGGCTAGAAACTGATGGTATGACTATTCAACTAAAAGTGAAGGAAGAGGTGTCTGGATGGGACCTTTTTCACGCTC
TACTTATTAGCTCTGCAAATGATGCTGCCAATGTTTTAGCAGATGCCTGCTGCCAAAGCGTCTCTGCTTTCATGCGCCAACTTAATGAGTTTTTGAGGGA
ACTCGGTTGCCAAAATACTCATTTTAATTCTCCTCATGGACTCCATCATCCTGATCACTACACGACAGCTAGAGATCTATCACTCATCATGAAAGAAGCT
TTAAAAGAGCCTCTTTTCCGCCAAGTCATTCACACAGCGTCCTATACCATGGAGGCCACCAACTTAAGTCCAGAAAGAGTTCTGTCTTCCACGAACAAAC
TTCTTTCTTCCTCTTCGACTTACTTTTATCCACCTTGTTTAGGAGGGAAAACAGGAACTACAAAAAGTGCAGGGAAAAATATCATTTTCGCTGCAGAAAA
GAACAATCGCTCAATTATTGTTGTAGCAGCAGGATATTTTGGCCCTGCTGCTCAACTATACCAAGATGCTATAGCTCTGTGCGAAGATCTATTTAATGAA
CAGCTATTACGATGCTTTTTAATCCCTCCCGCAAGTCACTATCCTGTACCAACTCGATTTGGCACTGTGACAGCTCCGGTAGCACAAGGCATTTATTACG
ACTTTTATCCTTCCGAAGAGATCCCCTCTTAA
SEQ ID 259:
MTANTFGILNILMKQAKADDLAQFLPEHLLLDSPHHQDIPLQSLSFNMRWLATIHPSWISVAMKEFPPVVQSQLLAWLPLPLTQELLPLLDSGVTPATKR
CLDFGAFYLLDLLSKKVRPPGITEEIFLPASPFNAMLYYVGPTKMALINCLGLYTLAQEMRNVVDRVVIDRVQRVLSETERMFLNYCKTHPMKHLEPMAF
LASWEEDQALRHFIHVQGLRFLARALAKEDSSFLWYFIRRLDVGRGYIFEKALQSSIDSPHNEYFRERLEHCISILVQ
SEQ ID 260:
GTGACAGCGAATACCTTTGGGATTCTTAATATCCTGATGAAGCAGGCAAAAGCTGATGATTTAGCTCAGTTTCTGCCGGAACATCTTCTACTAGATTCTC
CGCATCATCAGGATATTCCTCTGCAGTCCTTATCTTTCAATATGCGTTGGTTAGCAACCATTCATCCTTCCTGGATTAGTGTTGCTATGAAAGAATTCCC
TCCCGTTGTGCAATCGCAATTATTAGCTTGGTTACCTCTCCCTCTAACGCAAGAACTACTCCCTCTTTTAGATTCTGGAGTTACCCCTGCTACAAAACGC
TGCTTAGACTTTGGAGCTTTCTACCTACTTGACTTACTCAGTAAGAAAGTACGTCCTCCAGGCATTACAGAAGAGATTTTTCTCCCCGCTTCTCCTTTCA
ATGCTATGCTGTACTATGTAGGCCCTACCAAAATGGCCTTGATCAATTGTCTAGGGCTTTATACCTTAGCTCAAGAAATGCGAAACGTAGTCGATCGTGT
AGTCATTGATCGCGTGCAGCGTGTGTTATCCGAAACGGAACGGATGTTTCTAAATTATTGTAAAACACATCCTATGAAACATCTGGAACCTATGGCCTTT
TTAGCCTCTTGGGAGGAAGATCAAGCTTTACGTCATTTCATCCATGTTCAAGGTTTGCGCTTCTTAGCTCGCGCTCTAGCAAAAGAAGATAGCTCTTTCC
TTTGGTATTTTATTCGCAGACTTGATGTCGGAAGAGGCTATATTTTCGAAAAAGCATTGCAGAGTTCGATAGATAGTCCCCATAATGAGTATTTTCGAGA
GCGCTTAGAACACTGTATCAGTATTCTTGTGCAATAA
SEQ ID 261:
MWLIVASTLLACLAMALVFKAYRHVISFRSYVNQVIRDVRLSVDLKEWAVAEMRLAPILKKRQYRRKYLFEYIRILRELERFEEAEKLLGEAKKLKLAGA
HFFLEVAHKAFRHGAYKEAAHAFSLLSAELMGEREVARYTISLVYLGEVDAACRIIEPWIGPLAHQEVFISVGHIYFATKRYADAIDFYRRARSLGSCPI
DVLYNLAHSLRICGQYVDAGMLFRELLGDPVYKDEAMFNIGLCEQKLGNSKKALLIYQNSELWVRGDALMMRYAALAAADQQDYQLAEHCWTLAFRCQSY
ADDWNCCVHYGLALCHLKKYAEAEKVYLRVIQKTPDcLVACKALAWLAGVGHATMISAREGIAYAKRALQIKRSPEVLELLSACEAREGNFDVAYDIQAI
LAERDTTAKERERRSQILKNLRQKLPIDQQHIVEVSLLLAA
SEQ ID 262:
ATGTGGCTAATCGTAGCATCGACACTCTTGGCTTGCTTAGCGATGGCTTTAGTCTTTAAAGCTTATAGGCATGTTATCAGCTTCCGCAGCTACGTGAATC
AAGTGATACGGGATGTGCGCTTGAGCGTAGATTTAAAAGAGTGGGCGGTCGCAGAAATGCGCTTGGCCCCGATCCTGAAAAAACGTCAATATCGACGTAA
ATATTTATTCGAATATATCCGTATTCTTCGAGAGCTCGAACGTTTTGAAGAAGCTGAAAAGCTTTTGGGAGAAGCTAAGAAATTGAAATTAGCAGGTGCC
CATTTTTTCTTAGAGGTTGCACATAAGGCTTTCCGGCATGGCGCCTATAAAGAGGCTGCACATGCTTTTTCTCTTCTTTCCGCTGAGCTTATGGGCGAGC
GAGAGGTCGCTCGCTACACCATTTCTCTGGTATATCTTGGAGAAGTAGATGCTGCTTGTCGGATCATTGAACCATGGATTGGTCCACTTGCTCACCAAGA
AGTCTTTATTAGCGTAGGACATATCTATTTTGCGACGAAGCGCTATGCAGATGCTATCGATTTCTATCGACGCGCACGGTCCCTAGGATCTTGCCCTATC
GATGTTTTGTACAACTTAGCACATTCTTTGCGTATTTGCGGGCAGTATGTCGATGCTGGGATGCTCTTTAGAGAGCTTTTAGGGGATCCGGTTTATAAAG
ACGAAGCGATGTTTAATATCGGCTTATGTGAGCAAAAATTAGGGAATTCGAAAAAGGCTCTGCTGATCTATCAAAATAGTGAGTTATGGGTTCGCGGAGA
TGCTTTGATGATGCGGTATGCAGCTCTTGCGGCGGCGGATCAGCAAGATTATCAGCTCGCAGAGCACTGCTGGACATTAGCTTTCCGTTGTCAAAGTTAT
GCTGATGATTGGAATTGCTGTGTTCATTATGGTTTAGCATTATGCCATTTAAAGAAATATGCCGAGGCTGAGAAGGTATATTTAAGAGTGATTCAAAAGA
CTCCGGATTGTTTGGTTGCTTGTAAAGCACTGGCTTGGCTCGCAGGAGTCGGACATGCGACGATGATTTCTGCTCGAGAAGGAATAGCTTATGCTAAGCG
AGCGCTGCAGATCAAACGATCTCCGGAAGTACTCGAGTTATTGAGTGCTTGTGAAGCTCGAGAAGGTAATTTTGATGTTGCTTATGATATTCAGGCTATT
TTAGCCGAGCGAGATACGACGGCGAAGGAACGTGAGCGACGGTCACAGATTTTGAAGAATTTACGACAGAAACTTCCTATAGACCAACAGCATATAGTAG
AGGTTTCTTTACTGCTAGCTGCCTAG
Claims (13)
1.蛋白质在制造治疗或预防沙眼衣原体感染的药物中的应用,其中,所述蛋白质是(a)含有选自以下氨基酸序列的蛋白质:SEQ IDs 1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、33、35、37、39、41、43、45、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75、77、79、81、83、85、87、89、91、93、95、97、99、101、103、105、107、109、111、113、115、117、119、121、123、125、127、129、131、133、135、137、139、141、143、145、147、149、151、153、155、157、159、161、163、165、167、169、171、173、175、177、179、181、183、185、187、189、191、193、195、197、199、201、203、205、207、209、211、213、215、217、219、221、223、225、227、229、231、233、235、237、239、241、243、245、247、249、251、253、255、257、259和261,(b)含有与(a)中的氨基酸序列具有50%或更高一致性的氨基酸序列的蛋白质,或(c)含有(a)中氨基酸序列片段的蛋白质。
2.核酸在制造治疗或预防沙眼衣原体感染的药物中的应用,其中,所述核酸是(a)含有选自以下核苷酸序列的核酸:SEQ IDs 2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、34、36、38、40、42、44、46、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76、78、80、82、84、86、88、90、92、94、96、98、100、102、104、106、108、110、112、114、116、118、120、122、124、126、128、130、132、134、136、138、140、142、144、146、148、150、152、154、156、158、160、162、164、166、168、170、172、174、176、178、180、182、184、186、188、190、192、194、196、198、200、202、204、206、208、210、212、214、216、218、220、222、224、226、228、230、232、234、236、238、240、242、244、246、248、250、252、254、256、258、260和262。
3.&242,(b)含有的序列与(a)中的核苷酸序列具有50%或更高一致性的核苷酸序列的核酸,或(c)含有(a)中核苷酸序列片段的核酸。
4.如权利要求1或2所述的应用,其中,治疗或预防感染是用激发免疫应答的药物来完成的,该免疫应答是衣原体原生小体特异性的。
5.如权利要求1所述的蛋白质或如权利要求2所述的核酸在制造用于中和沙眼衣原体原生小体的药物中的应用。
6.一种含蛋白质和佐剂的免疫原性组合物,其中,所述蛋白质是(a)含有选自以下氨基酸序列的蛋白质:SEQ IDs 1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、33、35、37、39、41、43、45、47、49、51、53、55、57、59、61、63、65、67、69、71、73、75、77、79、81、83、85、87、89、91、93、95、97、99、101、103、105、107、109、111、113、115、117、119、121、123、125、127、129、131、133、135、137、139、141、143、145、147、149、151、153、155、157、159、161、163、165、167、169、171、173、175、177、179、181、183、185、187、189、191、193、195、197、199、201、203、205、207、209、211、213、215、217、219、221、223、225、227、229、231、233、235、237、239、241、243、245、247、249、251、253、255、257、259和261,(b)含有与(a)中的氨基酸序列具有50%或更高一致性的氨基酸序列的蛋白质,或(c)含有(a)中氨基酸序列片段的蛋白质。
7.一种含核酸和佐剂的免疫原性组合物,其中,所述核酸是(a)含有选自以下核苷酸序列的核酸:SEQ IDs 2、4、6、8、10、12、14、16、18、20、22、24、26、28、30、32、34、36、38、40、42、44、46、48、50、52、54、56、58、60、62、64、66、68、70、72、74、76、78、80、82、84、86、88、90、92、94、96、98、100、102、104、106、108、110、112、114、116、118、120、122、124、126、128、130、132、134、136、138、140、142、144、146、148、150、152、154、156、158、160、162、164、166、168、170、172、174、176、178、180、182、184、186、188、190、192、194、196、198、200、202、204、206、208、210、212、214、216、218、220、222、224、226、228、230、232、234、236、238、240、242、244、246、248、250、252、254、256、258、260和262,(b)含有的序列与(a)中的核苷酸序列具有50%或更高一致性的核苷酸序列的核酸,或(c)含有(a)中核苷酸序列片段的核酸。
8.如权利要求5或6所述的组合物用作药物。
9.一种中和患者沙眼衣原体感染的方法,其特征在于,所述方法包括给予患者权利要求5或6所述的组合物或能识别权利要求1所述的蛋白质的抗体的步骤。
10.一种免疫患者抗沙眼衣原体感染的方法,其特征在于,所述方法包括给予患者权利要求5或6所述的组合物。
11.一种产生沙眼衣原体原生小体特异性抗体的方法,其特征在于,所述方法包括给予患者权利要求5或6所述的组合物。
12.一种产生能识别权利要求1所定义的蛋白质的抗体的方法,其特征在于,所述方法包括给予患者沙眼衣原体原生小体的步骤。
13.一种在生物样品中检测沙眼衣原体原生小体的方法,其特征在于,所述方法包括使样品与能识别权利要求1所定义的蛋白质的抗体接触的步骤。
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GB0129732.4 | 2001-12-12 | ||
GB0129732A GB0129732D0 (en) | 2001-12-12 | 2001-12-12 | Immunisation against chlamydia trachomatis |
GB0218233.5 | 2002-08-06 | ||
GB0218233A GB0218233D0 (en) | 2001-12-12 | 2002-08-06 | Immunisation against chlamydia trachomatis |
GB0218924A GB0218924D0 (en) | 2001-12-12 | 2002-08-14 | Immunisation against chlamydia trachtomatis |
GB0218924.9 | 2002-08-14 |
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WO2009062399A1 (en) * | 2007-11-05 | 2009-05-22 | Shanghai Jiaotong University | Peptide ligand directed drug delivery |
CN101855237A (zh) * | 2007-11-05 | 2010-10-06 | 上海交通大学 | 肽配体定向药物递送 |
CN101855237B (zh) * | 2007-11-05 | 2014-10-22 | 上海交通大学 | 肽配体定向药物递送 |
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NZ546711A (en) | 2008-06-30 |
EP2168596B1 (en) | 2012-05-23 |
CA2469620A1 (en) | 2003-06-19 |
EP2335724A1 (en) | 2011-06-22 |
ES2312649T3 (es) | 2009-03-01 |
JP4413617B2 (ja) | 2010-02-10 |
US7361353B2 (en) | 2008-04-22 |
US20060216308A1 (en) | 2006-09-28 |
WO2003049762A3 (en) | 2004-05-13 |
US20080305112A1 (en) | 2008-12-11 |
KR100982204B1 (ko) | 2010-09-14 |
ATE406912T1 (de) | 2008-09-15 |
AU2002366592A1 (en) | 2003-06-23 |
RU2331435C2 (ru) | 2008-08-20 |
AU2002366592B2 (en) | 2008-01-10 |
EP1463520A2 (en) | 2004-10-06 |
RU2004121149A (ru) | 2005-04-20 |
EP1463520B1 (en) | 2008-09-03 |
JP2005511076A (ja) | 2005-04-28 |
EP2168596A3 (en) | 2010-07-28 |
US20050106162A1 (en) | 2005-05-19 |
US7842297B2 (en) | 2010-11-30 |
JP2011250797A (ja) | 2011-12-15 |
KR20040074085A (ko) | 2004-08-21 |
ES2386386T3 (es) | 2012-08-20 |
NZ533428A (en) | 2008-03-28 |
CN100515494C (zh) | 2009-07-22 |
NZ562929A (en) | 2009-07-31 |
EP2335723A1 (en) | 2011-06-22 |
DE60228758D1 (de) | 2008-10-16 |
WO2003049762A2 (en) | 2003-06-19 |
EP2168596A2 (en) | 2010-03-31 |
JP2009072192A (ja) | 2009-04-09 |
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