BRPI0709896A2 - proteìnas de fusão entre enzimas degradadoras da parede de celular de plantas e uma swolenina, e seus usos - Google Patents

Abstract

<B>PROTEìNAS DE FUSãO ENTRE ENZIMAS DEGRADADORAS DA PAREDE DE CELULAR DE PLANTAS E UMA SWOLENINA, E SEUS USOS <D>A invenção refere-se a proteínas de fusão compreendendo pelo menos uma swolenina e pelo menos uma enzima degradadora da parede celular de plantas, a referida swolenina e a enzima degradadora da parede celular de plantas sendo proteínas recombinantes correspondendo a proteínas nativas em fungos, ou suas formas mutadas. A invenção também se refere ao uso de proteínas de fusão conforme definidas acima, para realizar processos de degradação da parede celular de plantas no âmbito da preparação, a partir de plantas ou subprodutos vegetais, de compostos de interesse localizados na parede celular de plantas, ou no âmbito do branqueamento da polpa e do papel, para a produção de biocombustíveis ou nas indústrias alimentícias.

Description

Relatório Descritivo da Patente de Invençãopara "PROTEÍNAS DE FUSÃO ENTRE ENZIMASDEGRADADORAS DA PAREDE DE CELULAR DEPLANTAS E UMA SWOLENINA, E SEUS USOS".

A invenção refere-se à construção esuperprodução de proteínas de fusão multifuncionais criadas porengenharia genética entre pelo menos uma swolenina e pelomenos uma enzima degradadora da parede celular de plantas, e aseus usos como ferramentas enzimáticas aperfeiçoadas para avalorização de subprodutos agrícolas.

ANTECEDENTES DA INVENÇÃO

A parede celular das plantas desenvolveu umaarquitetura complexa com uma composição intrínseca de diversoscarboidratos para, dessa forma, proteger a célula de ataquesmicrobianos. Como conseqüência, os microorganismosdegradadores da parede celular de plantas desenvolveram diversossistemas enzimáticos com o intuito de decompor a biomassavegetal e, finalmente, assimilar os substratos de açúcares. Dentreos microorganismos bacterianos e fúngicos, são encontradasenzimas modulares contendo Módulos de Ligação a Carboidratos(CBMs) que auxiliam as enzimas no direcionamento aossubstratos. Recentemente, foi identificado, no Trichodermareesei, uma nova espécie de proteína, envolvida na dissolução daparede celular de plantas, a qual foi chamada de "swolenina"(Saloheimo M. e col. 2002). Essa proteína apresenta altasimilaridade com as expansinas das plantas, que decompõe asligações de hidrogênio entre as microfibrilas de celulose, ou acelulose e outros polímeros da parede celular (Cosgrove 2000).De fato, imagina-se que as expansinas das plantas desempenhamuma função da extensão da parede celular, sendo consideradas umregulador endógeno fundamental para o crescimento da paredecelular da planta (Li Y e col. 2003). Ao contrário das expansinasde plantas, a swolenina tem uma estrutura bimodular composta deum CMB conectado por uma região de ligação ao domíniohomólogo da expansina de plantas. Essa estrutura modular étípica das celulases fungicas e de algumas hemicelulases queapresentam um CBM para direcionar o módulo enzimático. Nocaso específico da swolenina, não há atividade hidrolíticaassociada, mas sim um módulo de expansina com capacidade dedissolução da parede celular. Paralelamente, a célula dosmicroorganismos desenvolveu sistemas livres que não possuemum módulo CBM, sendo em vez disso segregados em grandesquantidades no meio extracelular. Esses tipos de enzimas podemser encontrados nas celulases, hemicelulases e pectinases. Osestudos de engenharia genética têm se focado no aperfeiçoamentodas enzimas livres por meio da associação de um módulo CBMpara direciojiar enzimas a um substrato especifico da planta, talcomo a celulose (Ito e col. 2004; Limón e col. 2004). No primeirocaso, Ito e col. demonstraram que a atividade hidrolítica de umeendoglucanase de T. reesei foi aumentada com o número de CBMadicionado à enzima. No segundo trabalho, um módulo CBM foigeneticamente fusionado a uma enzima sem ser de celulase, aquitinase de Trichoderma harzanium, e os resultados mostraramque tanto as atividades antifungicas como da quitinaseaumentaram com o aumento da capacidade de ligação à celulose.Esse ganho de desempenho é de grande interesse para aplicaçõesindustriais em que a degradação da parede celular de plantas é umponto essencial, por exemplo, nos setores de biocombustíveis e depolpa e papel.

Recentemente, os inventores passaram a seinteressar em cinamoil esterases capazes de hidrolizar diferentestipos de ácidos hidroxicinâmicos ligados a ésteres de açüc,e,Essas enzimas foram classificadas com base na especificidade dosubstrato e na identidade de seqüência primária (Crepin e col.2003). As primeiras cinamoil esterases a serem totalmentecaracterizadas pertencem ao Aspergillus niger. A feruloil esterase(FAEIII, tipo A) foi descrita como sendo preferivelmente ativacontra o éster metílico de ácidos ferúlicos e sinápicos (Faulds eWilliamson 1994), ao passo que a cinamoil esterase demonstrouter preferência pelo éster metílico de ácidos caféicos e p-coumáticos (Kroon e col. 1996). Ambos os genes codificadoresforam clonados e caracterizados. Eles foram superexpressos emPichia pastoris e A. niger para produzir quantidades suficientesde proteínas recombinantes e permitir sua utilização emaplicações industriais (Juge e col. 2001 ; Record e col. 2003,Levasseur e col. 2003). A feruloil esterase foi avaliada quanto aobranqueamento da palha de trigo e da polpa de linho, emcombinação com um tratamento com lacase, a redução do teorfinal de lignina (Record e col. 2003; Sigoillot e col; 2005). Defato, a feruloil esterase é conhecida por hidrolizaroligossacarídeos feruloilados, mas também ligações cruzadas dediferulato encontradas na hemicelulose e na pectina (Williamsone col. 1998; Saulnier e Thibault 1999), facilitando o acesso deoutros enzimas lignocelulolíticas.

O objetivo do presente trabalho é o dedesenvolver novas ferramentas enzimáticas para degradar abiomassa vegetal ou biotransformar os componentes da paredecelular de plantas. Duas estratégias foram desenvolvidasparalelamente. Em um trabalho anterior (Levasseur e col. 2004), oobjetivo era o de desenvolver um novo tipo de enzima fúngicafusionada a uma doquerina bacteriana que posse, portanto, capazde ser incorporada em celulossomas da Clostridiumthermocellum. De fato, a celulosoma bacteriana é um sistemamuito eficaz no aumento do efeito sinérgico das enzimas (Ciruelae col. 1998, Fierobe e col. 2002). De forma alternativa,demonstrou-se que enzimas quiméricas associando duas enzimaspossuem grande eficácia na degradação da biomassa vegetal,especialmente se um módulo CBM tiver sido integrado nocomplexo enzimático(Levasseur e col 2005. Em outrostrabalhos, a fusão dos módulos CBM aos parceiros enzimáticosdemonstrou ser uma boa maneira de melhorar a eficiência doparceiro enzimático pelo auxílio do direcionamento enzimático ao25 substrato e pelo aumento da concentração local das enzimas(Pages et al. 1997, Boraston et al. 2004). Além disso, foiverificado que apenas alguns CBMs mediam o efeito dedissolução não-catalítica da estrutura cristalina da celulose (Din ecol. 1994, GaoecoL 2001).

Na presente invenção, os inventores descrevempela primeira vez a associação de uma swolenina a uma enzimadegradadora da parede celular de plantas, tal como a feruloilesterase utilizada como modelo enzimático, utilizando-se umafusão genética de ambos os genes correspondentes.

SUMÁRIO DA INVENÇÃOA presente invenção se baseia na demonstraçãodo efeito da eficiência enzimática, relacionado à associação físicaem uma única proteína quimérica, de enzimas degradadoras daparede celular de plantas e da swolenina, quando comparado aouso das enzimas livres degradadoras da parede celular de plantas.

Assim, o principal objetivo da presenteinvenção é obter novas proteínas de fusão entre a swolenina eenzimas de degradação da parede celular de plantas.

Outro objetivo da presente invenção é o depropor um novo processo para a preparação dos compostos deinteresse ligados às paredes das células vegetais, por meio da

„aplicacão. das_referidas___proteínas- de—fusão—às -plantas^—e—

vantajosamente aos subprodutos agrícolas, como substratos.

BREVE DESCRIÇÃO DOS DESENHOSA Figura 1 representa a produção da Feruloilesterase (FAEA) em Trichoderma reesei. A atividade da feruloilesterase foi medida no meio extracelular obtido a partir dosmelhores transformantes FAEA de T. reesei Rut-C (·) e CL847(■). Utilizou-se ferulato de metila como substrato para testes deatividade.

A Figura 2 ilustra a análise Western blot e onúmero de cópia dos cassetes integrados no genoma de T. reesei.Utilizaram-se anticorpos contra FAEA para a imunodetecção daFAEA e transformantes SWOI-FAEA a partir do meioextracelular total. Pista 1 e 2: transformantes Rut-C30 produzindoFAEA e SWOI-FAEA, respectivamente. Pista 3 e 4:transformantes CL847 produzindo FAEA e SWOI-FAEA,respectivamente. O número de cópia dos cassetes de expressão foiestimado pela análise Southern blot. Utilizou-se o BRFM dalinhagem de Aspergillus niger do tipo selvagem como controlecontendo a cópia do gene faeA. Sd: padrões de peso molecular.

A Figura 3 representa um gel SDS-PAGE deproteínas extracelulares e purificadas de Trichoderma reesei.Pista 1: linhagem CL847 de T. reesei não-transformada. Pista 2 e3: Meio extracelular total da linhagem CL847 de T. reeseitransformado pelos cassetes de expressão para produção de FAEAou SWOI-FAEA, respectivamente. Pistas 4 e 5: FAEA é SWOI-faea PURIFICADOS sD: padroes de peso molecular.

A Figura 4 mostra a estabilidade de temperaturada FAEA e SWOI-FAEA obtidas da linhagem 847 deTrichoderma reesei. A atividade da proteína purificada (♦) eSWOI-FAEA (■) após 60 min de incubação à temperaturaindicada é representada. Utilizou-se ferulato de metila comosubstrato para testes de atividade.

A Figura 5 ilustra a liberação de ácido ferúlicoutilizando-se a FAWA ou SWOI-FAEA de Trichoderma reeseiCL847. Utilizou-se farelo de trigo como substrato, sendo aliberação de ácido ferúlico determinada por HPLC após 4 h(barras brancas), 16 h (barras cinzas) e 24 h (barras pretas) dehidrólise. As atividades foram expressas como a porcentagem daconcentração total de ácido ferúlico no farelo de trigo. R:referência contendo apenas o tampão; S: meio extracelular dalinhagem não transformada; C: controle como a feruloil esterasede Aspergillus niger; F: feruloil esterase (FAEA) de T. reesei, S:Swolenina (SWOI) de T. reesei; proteína de fusão S-F (SWOI-FAEA) de T. reesei.

DESCRIÇÃO DETALHADA DA INVENÇÃO

A invenção refere-se a proteínas de fusão,compreendendo:

- pelo menos uma swolenina, isto é, umaproteína contendo um domínio de molécula de ligação acarboidratos (CBM) que direciona para a celulose das plantas, eum domínio_de. -expansina- que—decompõe—as- ligações—de-hidrogênio entre as microfibrilas da celulose,

- e pelo menos uma enzima degradadora daparede celular de plantas,a referida enzima sendo de tal forma que elacontém um domínio CBM ou não, contanto que contenha umCBM, o último pode ser excluído, se necessário, a referidaswolenina e a enzima degradadora da parede celular de plantassendo proteínas recombinantes correspondendo a proteínasnativas em fungos, ou formas mutadas destes.

A expressão "enzimas degradadoras da paredecelular de plantas" refere-se a enzimas que são capazes de efetuara digestão dos componentes de parede celular, como a celulose,hemicelulose e lignina. As enzimas degradadoras da paredecelular de plantas nas referidas proteínas de fusão são idênticas,ou diferentes uma da outra.

A expressão "molécula de ligação acarboidratos" refere-se a uma molécula com afinidade porcelulose, que direciona sua enzima associada à celulose.

A invenção refere-se mais especificamente aproteínas de fusão conforme definidas acima, em que a swoleninacorresponde a proteínas nativas, ou suas formas mutadas, defungos escolhidos dentre ascomicetes, como por exemplo:

- Linhagens de Trichoderma, e maisparticularmente Trichoderma reesei, ou

- linhagens de Aspergillusi e maispatícularmente Aspezgillus fumigatus. A invencão refere-se maisespecificamente a proteínas de fusão conforme definidas acima,em que a swolenina corresponde a enzimas nativas, ou suasformas mutadas, de linhagens de Trichoderma, tal como

Trichoderma reesei.A invenção refere-se mais especificamente aproteínas de fusão conforme definidas acima, em que a swoleninaé a proteína da Trichoderma reesei, representada pela:

- SEQ ID NO: 2 em seu estado pré-proteína, ouseja, contendo o peptídeo de sinal SEQ ID NO : 102 dos seguintes18 aminoácidos: MAGKLILVALASLVSLSI,

- ou pela SEQ ID NO : 4 em seu estado maduro,ou seja, sem o peptídeo de sinal supramencionado.

A invenção refere-se mais especificamente aproteínas de fusão conforme definidas acima, em que a swoleninacorresponde a enzimas nativas, ou suas formas mutadas, delinhagens de Aspergillus, tal como Aspergillus fumigatus.

A invenção refere-se mais especificamente aproteínas de fusão conforme definidas acima, em que a swoleninaé a proteína de Aspergillus fumigatus, representada pela:

- SEQ ID NO: 6 em seu estado pré-proteína, ouseja, contendo o peptídeo de sinal SEQ ID NO : 104 dos seguintes17 aminoácidos: MTLLFGIFLARLAVAAA,

- ou pela SEQ ID NO : 8 em seu estado maduro,ou seja, sem o peptídeo de sinal supramencionado.

A invencao refere-se, mais particulamente, aproteínas de fusão conforme definidas acima, em que as enzimasdegradadoras da parede celular de plantas são escolhidas dentreenzimas capazes de hidrolizar a celulose, a hemicelulose edegradar a lignina.A invenção refere-se mais particularmente aproteínas de fusão conforme definidas acima, em que as enzimasdegradadoras da parede celular de plantas são hidrolasesescolhidas dentre:

celulases, tais como endoglucanases,exoglucanases, tais como celobiohidrolases, ou β-glucosidases,

- hemicelulases, tais como xilanases,

- Iigninases capazes de degradar ligninas, taiscomo lacases, manganês peroxidases, lignina peroxidases,peroxidases versáteis ou enzimas suplementares, tais comocelobiose deidrogenases, e aril álcool oxidases,

- cinamoil éster hidrolases capazes de liberarácidos cinâmicos, tais como ácidos ferúlicos e de hidrolizarligações cruzadas de ácido diferúlico entre cadeias dehemicelulose, tais como feruloil esterases, cinamoil esterases eácido clorogênico hidrolases.

A invenção refere-se, mais especificamente, aproteínas de fusão conforme definidas acima, em que as enzimasdegradadoras da parede celular de plantas são escolhidas entreferuloil esterases, celobiohidrolases com ou sem seus domíniosCBM, endoglucanases com ou sem seus dominios CBM,xilanases e lacases.

A invenção refere-se, mais particularmente, aproteínas de fusão conforme definidas acima, em que as enzimasdegradadoras da parede celular de plantas correspondem aenzimas nativas, ou a suas formas mutadas, de fungosselecionados entre:

* ascomicetes, tal como:

linhagens de Aspergillusi e maisparticularmente Aspergillus niger,

linhagens de Trichoderma^ e maisparticularmente Triehoderma reesei,

linhagens de Magnaporthei e maisparticularmente Magnaporthe grisea,

* basidiomicetes, como linhagens dePycnoporus, Haloeiphina ou Phanerochaete, e maisparticularmente, Pycnoporus cinnabarinus, Pycnoporussanguineus ou Haloeyphina villosa, ou Phaneroehaeteehrysosporium.

A invenção refere-se mais especificamente aproteínas de fusão conforme definidas acima, em que as enzimasdegradadoras da parede celular de plantas correspondem aenzimas nativas, ou suas formas mutadas, de linhagens deAspergillus, tal como Aspergillus fumigatus.

A invenção refere-se mais especificamente a,proteímsdeJfusão^^ peio-menos

uma das enzimas degradadoras da parede celular de plantas é umaferuloil esterase, tal como a selecionada dentre:

- a feruloil esterase A de A. niger, representadapela SEQIDNO : 10,- ou a feruloil esterase B de A. niger,representada pelo SEQ ID NO : 12.

A invenção refere-se mais particularmente aproteínas de fusão conforme definidas acima, em que pelo menosuma das enzimas degradadoras da parede celular de plantas é umaxilanase, tal como a xilanase B de A. niger, representada pelaSEQIDNO : 14.

A invenção refere-se mais especificamente aproteínas de fusão conforme definidas acima, em que as enzimasdegradadoras da parede celular de plantas correspondem aenzimas nativas, ou suas formas mutadas, de linhagens deTrichoderma, tal como Trichoderma reesei.

A invenção refere-se mais especificamente aproteínas de fusão conforme definidas acima, em que pelo menosuma das enzimas degradadoras da parede celular de plantas é umacelobiohidrolase, tal como a selecionada dentre:

- A celobiohidrolase I de T. reesei, erepresentada pela SEQ ID NO : 16,

- a celobiohidrolase I de T. reesei, em que odomínio CBM foi deletado, e representada pela SEQ ID NO : 18,celobiGhidrolase- II de T reesei,erepresentada pela SEQ ID NO : 20,

- a celobiohidrolase II de T. reesei, em que odomínio CBM foi deletado, e representada pela SEQ ID NO : 22.

A invenção refere-se mais especificamente aproteínas de fusão conforme definidas acima, em que pelo menosuma das enzimas degradadoras da parede celular de plantas é umaendoglucanase, tal como a selecionada dentre:

- a endoglucanase I de T. reesei, e representadapela SEQID NO : 24,

- a endoglucanase I de T. reesei, em que odomínio CBM foi deletado, e representada pela SEQ ID NO : 26.

A invenção refere-se mais particularmente aproteínas de fusão conforme definidas acima, compreendendopeptídeos de ligação entre pelo menos duas das proteínascompreendidas nas referidas proteínas de fusão, os referidospeptídeos de ligação sendo polipeptídeos de 10 a 100aminoácidos, de preferência de cerca de 50 aminoácidos.

A invenção refere-se mais especificamente aproteínas de fusão conforme definidas acima, em que um peptídeode ligação está incluído entre cada proteína compreendida nasreferidas proteínas de fusão.

A invenção também se refere maisespecificamente a proteínas de fusão conforme definidas acima,em que o peptídeo de ligação é um polipeptídeo hiperglicosilado,tal como a seqüência representada pela SEQ ID NO : 28, presentena celobiohidrolase B de A. niger.

A invenção refere-se mais particularmente aproteínas de fusão conforme descritas acima, escolhidas dentre asproteínas de fusão da swolenina de Trichoderma reeseirepresentada pela SEQ ID NO : 4, com:- a feruloil esterase A de A. niger, representadapela SEQ ID NO : 10, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 30,

- a feruloil esterase A de A. niger, representadapela SEQ ID NO : 10, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 10, e sendo representada pela SEQ ID NO :32,

- a feruloil esterase B de A. niger, representadapela SEQ ID NO : 12, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 34,

- a feruloil esterase B de A. niger, representadapela SEQ ID NO : 12, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 12, e sendo representada pela SEQ ID NO :36,

- a xilanase B de A. niger, representada pelaSEQ ID NO : 14, a referida proteína de fusão sendo representadapela SEQ ID NO : 38,

- a xilanase B de A. niger, representada pelaSEQ ID NO : 14, a referida proteína de fusão compreendendo aseqüência representada pela SEQ ID NO : 28 como um peptídeode ligação hiperglicosilado entre a SEQ ID NO : 4 e a SEQ IDNO : 14, e sendo representada pela SEQ ID NO : 40,- a celobiohidrolase I de T. reesei representadapela SEQ ID NO : 16, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 42,

- a celobiohidrolase I de T. reesei, representadapela SEQ ID NO : 16, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 16, e sendo representada pela SEQ ID NO :44,

- a celobiohidrolase I de T. reesei sem sua CBMendógena representada pela SEQ ID NO : 18, a referida proteínade fusão sendo representada pela SEQID NO : 46,

- a celobiohidrolase I de T. reesei, sem suaCBM endógena representada pela SEQ ID NO : 18, a referidaproteína de fusão compreendendo a seqüência representada pelaSEQ ID NO : 28 como um peptídeo de ligação hiperglicosiladoentre a SEQ ID NO : 4 e a SEQ ID NO : 18, e sendo representadapela SEQ ID NO : 48,

- a celobiohidrolase II de T. reesei pela SEQ IDNO : 20, a referida proteína de fusão sendo representada pelaSEQ ID NO : 50,

- a celobiohidrolase II de T. reesei, representadapela SEQ ID NO : 20, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 20, e sendo representada pela SEQ ID NO :52,

- a celobiohidrolase II de T. reesei sem suaCBM endógena representada pela SEQ ID NO : 22, a referidaproteína de fusão sendo representada pela SEQ ID NO : 54,

- a celobiohidrolase II de T. reesei, sem suaCBM endógena representada pela SEQ ID NO : 22, a referidaproteína de fusão compreendendo a seqüência representada pelaSEQ ID NO : 28 como um peptídeo de ligação hiperglicosiladoentre a SEQ ID NO : 4 e a SEQ ID NO : 22, e sendo representadapela SEQ ID NO : 56,

- a endoglucanase I de T. reesei representadapela SEQ ID NO : 24, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 58,

- a endoglucanase I de T. reesei, representadapela SEQ ID NO : 24, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 24, e sendo representada pela SEQ ID NO :60,

- a endoglucanase I de T. reesei sem sua CBMendógena representada pela SEQ ID NO : 26, a referida proteínade fusão sendo representada pela SEQ ID NO : 62,

- a endoglucanase I de T. reesei, sem sua CBMendógena representada pela SEQ ID NO : 26, a referida proteínade fusão compreendendo a seqüência representada pela SEQ IDNO : 28 como um peptídeo de ligação hiperglicosilado entre aSEQ ID NO : 4 e a SEQ ID NO : 26, e sendo representada pelaSEQ ID NO : 64.

A invenção refere-se mais especificamente aproteínas de fusão conforme descritas acima, escolhidas dentre asproteínas de fusão da swolenina de Aspergillus fumigatusrepresentada pela SEQ ID NO : 8, com:

- a feruloil esterase A de A. niger, representadapelo SEQ ID NO : 10, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 66,

- a feruloil esterase A de A. niger, representadapela SEQ ID NO : 10, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 10, e sendo representada pela SEQ ID NO :68,

- a feruloil esterase B de A. niger, representadapela SEQ ID NO : 12, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 70,

- a feruloil esterase B de A. niger, representadapela SEQ ID NO : 12, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 12, e sendo representada pela SEQ ID NO :72,- a xilanase B de A. niger, representada pelaSEQ ID NO : 14, a referida proteína de fusão sendo representadapela SEQ ID NO : 74,

- a xilanase B de A. niger, representada pelaSEQ ID NO : 14, a referida proteína de fusão compreendendo aseqüência representada pela SEQ ID NO : 28 como um peptídeode ligação hiperglicosilado entre a SEQ ID NO : 8 e a SEQ IDNO : 14, e sendo representada pela SEQ ID NO : 76,

- a celobiohidrolase I de T. reesei representadapela SEQ ID NO : 16, a referida proteína de fusão sendorepresentada pela SEQID NO : 78,

- a celobiohidrolase I de T. reesei, representadapela SEQ ID NO : 16, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 16, e sendo representada pela SEQ ID NO :80,

- a celobiohidrolase I de T. reesei sem sua CBMendógena representada pela SEQ ID NO : 18, a referida proteínade fusão sendo representada pela SEQ ID NO : 82,

- a celobiohidrolase I de T. reesei, sem suaCBM endógena representada pela SEQ ID NO : 18, a referidaproteína de fusão compreendendo a seqüência representada pelaSEQ ID NO : 28 como um peptídeo de ligação hiperglicosiladoentre a SEQ ID NO : 8 e a SEQ ID NO : 18, e sendo representadapela SEQ ID NO : 84,- a celobiohidrolase II de T. reesei pela SEQ IDNO : 20, a referida proteína de fusão sendo representada pelaSEQ ID NO : 86,

- a celobiohidrolase II de T. reesei, representadapela SEQ ID NO : 20, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 20, e sendo representada pela SEQ ID NO :88,

- a celobiohidrolase II de T. reesei sem suaCBM endógena representada pela SEQ ID NO : 22, a referidaproteína de fusão sendo representada pela SEQ ID NO : 90,

- a celobiohidrolase II de T. reesei, sem suaCBM endógena representada pela SEQ ID NO : 22, a referidaproteína de fusão compreendendo a seqüência representada pelaSEQ ID NO : 28 como um peptídeo de ligação hiperglicosiladoentre a SEQ ID NO : 8 e a SEQ ID NO : 22, e sendo representadapela SEQ ID NO : 92,

- a endoglucanase I de T. reesei representadapela SEQ ID NO : 24, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 94,

- a endoglucanase I de T. reesei, representadapela SEQ ID NO : 24, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 24, e sendo representada pela SEQ ID NO : 96,

- a endoglucanase I de T. reesei sem sua CBMendógena representada pela SEQ ID NO : 26, a referida proteínade fusão sendo representada pela SEQ ID NO : 98,

- a endoglucanase I de T. reesei, sem sua CBMendógena representada pela SEQ ID NO : 26, a referida proteínade fusão compreendendo a seqüência representada pela SEQ IDNO : 28 como um peptídeo de ligação hiperglicosilado entre aSEQ ID NO : 4 e a SEQ ID NO : 26, e sendo representada pelaSEQ ID NO : 100.

A invenção também se refere a ácidos nucléicoscodificando uma proteína de fusão conforme definida acima, emais particularmente ácidos nucléicos escolhidos entre a SEQ IDNO : 29 a 99 codificando a SEQ ID NO : 30 a 100, os referidosácidos nucléicos opcionalmente começando com a seqüência SEQID NO : 101 ou 103 codificando, respectivamente, os peptídeosde sinal SEQ ID NO : 102 ou 104 mencionados acima,localizados a montante dos aminoácidos da SEQ ID NO : 30 a100.

A invenção também se refere a vetorestransformados com um ácido nucléico conforme definido acima.

A invenção também se refere a célulashospedeiras transformadas com um ácido nucléico conformedefinido acima, usando um vetor conforme definido acima.A invenção também se refere a célulashospedeiras transformadas conforme definido acima, escolhidasentre células de fungos, tais como os fungos conforme definidosacima, e mais especificamente A. niger, A. fumigatus,Trichoderma reesei ou Pycnoporus cinnabarinus.

A invenção também se refere maisespecificamente a um processo para a preparação de proteínas defusão conforme definidas acima, compreendendo a cultura in vitrode células hospedeiras conforme definidas acima, a recuperação,e, se necessária, a purificação das proteínas de fusão produzidaspelas referidas células hospedeiras na cultura. A invenção refere-se, mais especificamente, ao uso de proteínas de fusão conformedefinidas acima, para realizar processos de degradação da paredecelular de plantas no âmbito da preparação a partir de plantas ousubprodutos vegetais, de compostos de interesse localizados naparede celular da planta, ou no âmbito do branqueamento dapolpa e do papel, para a produção de biocombustíveis ou nas® indústrias alimentícias.

A invenção também se refere, maisparticularmente, ao uso, conforme definido acima, para realizarprocessos de degradação de parede celular de plantas no âmbitoda preparação dos seguintes compostos de interesse:

- bioetanol,

- antioxidantes, como ácido ferúlico ou ácidocaféico, que são ácidos cinâmicos, e hidroxitirosol, ou ácidogálico,aromas, como vanilina ou ρ-hidroxibenzaldeído, obtidos da biotransformação do ácidoferúlico ou do ácido p-coumárico, respectivamente.

A invenção também se refere ao uso, conformedefinido acima, em que as referidas proteínas de fusão sãoadicionadas diretamente às plantas ou subprodutos vegetais comosubstratos para sua hidrólise.

A invenção também se refere ao uso, conformedefinido acima, em que células hospedeiras transformadas comácidos nucléicos codificando as referidas proteínas de fusão, taiscomo os fungos mencionados acima, mais especificamente A.niger e Pycnoporus cinnabarinus, são colocadas em contato comas referidas plantas ou subprodutos vegetais como substratos parasua hidrólise.

A invenção se refere mais especificamente a umprocesso de degradação da parede celular de plantas no âmbito dapreparação, a partir de plantas ou subprodutos vegetais, decompostos de interesse localizados na parede celular de plantas,caracterizado por compreender as seguintes etapas:

- o tratamento enzimático de plantas ousubprodutos vegetais ou resíduos industriais, com proteínas defusão conforme definidas acima, ou com células transformadasconforme definido acima,

- opcionalmente, o tratamento físico de plantasou subprodutos vegetais por explosão a vapor em combinaçãocom a ação das proteínas de fusão,- opcionalmente a biotransformação commicroorganismos ou enzimas apropriados dos compostos contidosnas paredes celulares e liberados destas durante o tratamentoenzimático anterior,

- a recuperação, e se necessária, a purificação docomposto de interesse liberado pelas paredes celulares durante otratamento enzimático anterior ou obtido durante a etapa debiotransformação anterior.

De preferência, as plantas tratadas comproteínas de fusão no processo de acordo com a invenção sãoselecionadas entre beterraba, trigo, milho, arroz, ou todas asárvores usadas nas indústrias papeleiras.

De preferência, os subprodutos vegetais ouresíduos industriais tratados com proteínas de fusão no processode acordo com a invenção são selecionados entre palha de trigo,farelo de milho, farelo de trigo, farelo de arroz, bagaço de maçã,bagaço de café, subprodutos do café e água residual de usinas deoliva.

A invenção refere-se, mais particularmente, aum processo, conforme definido acima, para a preparação deantioxidantes, tais como ácidos cinâmicos, e mais especificamenteácido ferúlico, como compostos de interesse, o referido processocompreendendo: o tratamento das plantas ou subprodutos vegetaiscom proteínas de fusão conforme definido acima compreendendouma da swolenina mencionada acima e pelo menos uma dasenzimas degradadoras da parede celular: feruloil esterases, comoa feruloil esterase Aea feruloil esterase B, xinalanases, como axilanase B, tal como definida acima, a recuperação, e, senecessária, a purificação, dos antioxidantes liberados das paredescelulares das referidas plantas ou subprodutos vegetais. De formavantajosa, no âmbito da preparação de antioxidantes, tal comoácido ferúlico, as plantas tratadas com as proteínas de fusãodefinidas acima são escolhidas entre as seguintes: beterraba, trigo,trigo, arroz, subprodutos vegetais ou resíduos industriais tratadoscom proteínas de fusão definidas acima, sendo selecionadosdentre o seguinte: palha de trigo, farelo de milho, farelo de trigo,farelo de arroz, bagaço de maçã, bagaço de café, subprodutos docafé, água residual de usinas de oliva.

A invenção refere-se ainda a um processo,conforme definido acima, para a preparação de aromas comocompostos de interesse, o referido processo compreendendo:

- o tratamento de plantas ou subprodutosvegetais com as proteínas de fusão conforme definidas acima,usadas no âmbito da preparação dos antioxidantes, conformedefinido acima,

- a biotransformação dos compostos liberadospelas paredes celulares durante a etapa anterior, pela colocaçãodos referidas compostos em contato com enzimas não definidasproduzidas por microorganismos selecionados entre ascomicetesou basidiomicetes, tal como A. niger ou P. cinnabarinus,respectivamente,- a recuperação, e, se necessária, a purificação,dos aromas obtidos na etapa de biotransformação anterior.

A invenção refere-se, mais particularmente, aum processo conforme definido acima, para a preparação devanilina como o aroma de interesse, em que a proteína de fusãousada é selecionada entre as usadas para a preparação de ácidoferúlico conforme definido acima, e a etapa de biotransformação érealizada colocando o ácido ferúlico liberado pelas paredescelulares em contato com enzimas não definidas produzidas porascomicetes ou basidiomicetes, tal como A. niger ou P.cinnabarinus, respectivamente.

De forma vantajosa, as plantas e subprodutosvegetais, ou resíduos industriais usados no âmbito da preparaçãodos aromas, tal como vanilina, são selecionados entre osmencionados acima para a preparação dos antioxidantes.

A invenção refere-se ainda a um processo,conforme definido acima, para a preparação de bioetanol como ocomposto de interesse, o referido processo compreendendo:

- o tratamento das plantas ou subprodutosvegetais com proteínas de fusão conforme definido acimacompreendendo uma da swolenina mencionada acima e pelomenos uma das enzimas degradadoras da parede celular: Feruloilesterases, como a feruloil esterase Aea feruloil esterase B,xilanases, como a xilanase B, celulases, como a endoglucanase I,celobiohidrolase I e celobiohidrolase II, tal como definido acima,o referido tratamento sendo preferivelmente combinado com umtratamento físico das referidas plantas ou subprodutos vegetais,

- a biotransformação das plantas ou subprodutosvegetais tratados obtidos pela etapa anterior em açúcaresfermentáveis, pelo uso das proteínas de fusão descritas acima oucom um fungo transformado segregando as referidas proteínas defusão, em combinação com enzimas selecionadas entre celulases,hemicelulases ou esterases, ou microorganismos selecionadosentre ascomicetes, tal como A. niger ou Trichoderma reesei,

- a biotransformação dos açúcares fermentáveisem bioetanol por levedura;

De maneira vantajosa, as plantas e subprodutosvegetais ou resíduos industriais usados no âmbito da preparaçãodo bioetanol são selecionados entre os seguintes: madeira, plantasanuais ou subprodutos agrícolas.

A invenção também se refere a um processopara o branqueamento da polpa e do papel, o referido processocompreendendo:

- o tratamento químico e físico das plantas ousubprodutos vegetais em combinação com proteínas de fusãoconforme definidas acima compreendendo uma da swoleninamencionada acima e pelo menos uma das seguintes enzimasdegradadoras da parede celular: Feruloil esterases, como a feruloilesterase Aea feruloil esterase B, xilanases, como a xilanase B,ligninases, como as lacases, manganês peroxidases, ligninaperoxidases, peroxidases versáteis, ou enzimas suplementarescomo celobiose deidrogenases, e álcool arílico oxidases, tal comodefinido acima,

- opcionalmente, a biopolpação das plantas ousubprodutos vegetais tratados obtidos na etapa anterior, com umfungo transformado, tal como P. cinnabarinus, T. reesei ou A.niger, segregando proteínas de fusão conforme definidas acima,compreendendo uma da swolenina mencionada acima e pelomenos uma das seguintes enzimas degradadoras da parede celularde plantas: feruloil esterases, como a feruloil esterase Aeaferuloil esterase B, xilanases, como a xilanase B, ligninasescapazes de degradar ligninas, como as lacases, manganêsperoxidases, lignina peroxidases, peroxidases versáteis, ouenzimas suplementares como celobiose deidrogenases, e álcoolarílico oxidases, como definido acima,

- o biobranqueamento das plantas ousubprodutos vegetais tratados obtidos na etapa anterior comproteínas de fusão conforme definidas acima compreendendo umada swolenina mencionada acima e pelo menos uma das seguintesenzimas degradadoras da parede celular: feruloil esterases, comoa feruloil esterase Aea feruloil esterase B, xilanases, como axilanase B, ligninases capazes de degradar ligninas, como aslacases, manganês peroxidases, lignina peroxidases, peroxidasesversáteis, ou enzimas suplementares como celobiosedeidrogenases, e álcool arílico oxidases, tal como definido acima.

A invenção é ilustrada adicionalmente nadescrição detalhada seguinte da preparação e das propriedades daproteína de fusão entre uma swolenina e uma enzima degradadorada parede celular de plantas, tal como a esterase feruloil.

Resumidamente, a ação de uma proteína do tipoexpansina foi avaliada, em combinação física com a feruloilesterase, para a liberação de ácidos ferúlicos, que são compostosde alto valor derivados de produtos agrícolas. Esse ácidohidroxicinâmico é um ácido aromático atrativo, conhecido comoantioxidante e precursor aromático, nos setores alimentício efarmacêutico. A enzima recombinante foi produzida em T. reesei,conhecido por ser um hospedeiro muito eficaz, para segregar umagrande quantidade de proteínas extracelulares de interesseindustrial. A nova enzima recombinante foi caracterizada epurificada para ser testada em um substrato natural. Finalmente, alinhagem recombinante produzindo a enzima multimodular foicomparada com a linhagem parental para avaliar a capacidade dalinhagem quanto à liberação de ácido ferúlico.

O objetivo do presente trabalho era estudar oefeito da associação de uma nova categoria de proteína, aswolenina de T. reesei (Saloheimo e col. 2002), que estáenvolvida na dissolução da estrutura da parede celular, a umdomínio catalítico. Para o parceiro enzimático, uma enzimasuplementar livre, a feruloil esterase de A. niger, foi selecionadacomo modelo. Ao contrário dos módulos CBM convencionais, aswolenina fungica é composta de dois domínios diferentes, umsendo responsável pelo direcionamento aos substratos eidentificado como um CBM. O segundo domínio apresenta fortesimilaridade com as expansinas de plantas que foram propostaspara dissolver a ligação de hidrogênio entre as microfibrilas dacelulose sem ter atividade hidrolítica (Cosgrove 2000, Li e col. Ecol. 2003). O gene da swolenina foi expresso em levedura e em A.niger (Saloheimo e col. 2002) e ensaios de atividade foramanalisados em fibras de algodão, papéis-filtro e nas paredescelulares da alga Valonia. A swolenina de T. reesei demonstroumodificar a estrutura das fibras de celulose sem quantidadesdetectáveis de açúcares redutores. Além disso, o efeito daswolenina foi atribuído principalmente ao domínio da expansina,e especialmente à celulose das fibras de algodão e papéis-filtro.Como conclusão, imagina-se que a swolenina seja um bomcandidato para representar o "fator de intumescimento", Cl, comoum componente não hidrolítico necessário para tornar o substratomais acessível aos componentes hidrolíticos, Cx (Reese et ai.1950).

O potencial biotecnológico de tal proteína émuito atrativo no contexto da valorização da biomassa vegetal e oefeito do enxerto físico da swolenina na esterase feruloil para aliberação de ácido ferúlico foi estudado. Assim, esse trabalhorepresenta o primeiro trabalho da associação de três domíniosdiferentes e complementares em uma única ferramenta enzimáticapara uma ação integrante de direcionamento, dissolução ehidrólise. A produção da proteína quimérica foi obtida em duaslinhagens industriais de T. reesei, RutC30 e CL847, com oobjetivo de comparar a capacidade de produção das duaslinhagens. O Τ. reesei é um fungo filamentoso bem conhecido,utilizado pelo setor industrial pela sua incrível capacidade deproduzir celulases (Montenecourt e Eveleigh 1979, Durand e col.1988), sendo uma linhagem de referência para a produção denovas enzimas a nível industrial. Paralelamente, a produçãoheteróloga da FAEA separadamente foi realizada para serutilizada como controle em nossos ensaios de aplicação.

Com o objetivo de avaliar o efeito gerado pelaproximidade física de ambos os parceiros, a SWO (SEQ ID NO :4) foi fiisionada a montante da FAEA (SEQ ID NO : 10) sempeptídeo de ligação. Portanto, a SWOI foi utilizada como proteínatransportadora para facilitar a secreção da FAEA heteróloga. Paraa produção da FAEA, o peptídeo de sinal da FAEA foi mantidopara direcionar a secreção da proteína. As proteínasrecombinantes, FAEA e SWOI-FAEA (SEQ ID NO : 30) foramproduzidas com êxito por ambas as linhagens de T. reesei. Comrespeito à FAEA, a linhagem CL 847 demonstrou produzirrendimentos maiores se comparado à linhagem Rut-C30, isto é,70 contra 30 mg l-1, enquanto que para a proteína SWOI-FAEA, aprodução atingiu o mesmo nível de 25 mg Γ1 para ambas aslinhagens.

A eficiência da proteína SWOI-FAEAquimérica foi testada quanto à liberação de ácido ferúlico usandofarelo de trigo desamidado como substrato. Nesses ensaios deaplicação, o substrato não foi pré-tratado pela temperatura, umavez que as propriedades de dissolução e intumescimento daswolenina devem ser um indicador específico da ação da proteínasobre o substrato. O ácido ferúlico foi liberado com concentraçõessimilares usando a FAEA obtida de A. niger (Record e col. 2003)ou T. reesei. Esse resultado confirma que ambas as proteínas têmas mesmas propriedades, mesmo se forem produzidas por duaslinhagens de hospedeiros diferentes. Se a swolenina livre fosseadicionada à FAEA, nenhuma liberação adicional foi observada.Por outro lado, foi observado um aumento de 50% na liberação deácido ferúlico com a SWOI-FAEA se comparado à ação dosmódulos livres correspondentes. Além disso, a linhagem de T.reesei produzindo a proteína SWOI-FAEA quimérica foi avaliadapara estimar a capacidade da linhagem transformada quanto àliberação do ácido ferúlico. Usando o meio extracelularconcentrado de T. reesei CL847 por um curto período deincubação de 4 h, 45% do ácido ferúlico total foram obtidos,correspondendo a 1,8 g de ácido ferúlico por kg de farelo de trigo.Como conclusão, nossos testes de aplicação demonstraram que a9 SWOI-FAEA é mais eficiente para a liberação de ácido ferúlicose comparada ao módulo livre SWOI e FAEA. O efeito positivopoderia ser o resultado do direcionamento ao substrato da proteínadevido ao CBM endógeno da SWOI. Assim, o CBM da SWOIpoderia aumentar a concentração local da enzima para aproximidade do substrato e aumentar os rendimentos finais dahidrólise. Além disso, a eficiência da proteína quimérica poderiaser aperfeiçoada pela mobilidade específica do módulo deexpansina da SWOI (Cosgrove e col. 2000). De fato, supõe-se queo módulo de expansina facilite a difusão lateral da FAEA aolongo da superfície das microfibrilas da celulose, e ao mesmotempo dissolva a estrutura da parede celular, ambas as açõessendo sinérgicas para a liberação final do ácido ferúlico. Naverdade, o parceiro de swolenina da enzima quimérica deveráfacilitar o acesso do módulo catalítico aumentando o espectro deação da enzima para a área menos acessível.

Esse estudo demonstra pela primeira vez oefeito positivo da proximidade física de uma enzimacomplementar a uma proteína envolvida na dissolução da paredecelular. Portanto, essas ferramentas enzimáticas representam umaalternativa não poluente e um processo de custo reduzido para oprocesso biotecnológico existente de biotransformação deprodutos agrícolas. Por exemplo, tais enzimas quiméricas podemser usadas na produção de polpa e papel, e bioetanol, com outrascombinações de parceiros, dependendo das aplicaçõesbiotecnológicas.

EXEMPLOS

Materiais e métodos

Linhagens

Utilizou-se Echerichia coli JM 109 (Promega,Charbonnieres, França) para a construção e propagação dosvetores. A linhagem Rut-C30 (Montenecourt a Eveleigh 1979) eCL847 (Durand e col. 1998) de Triehoderma reesei foi utilizadapara expressão heteróloga usando os diferentes cassetes deexpressão.Meios e condições de culturaAs linhagens de T. reesei foram mantidas emtubos inclinados contendo ágar-batata-dextrose (Difco, Sparks,MD). Os transformantes foram regenerados em meio sólidomínimo contendo, por litro: (NH4)2SO4 5,0 g, KH2PO4 15,0 g,CaCl2 0,45 g, MgSO4 0,6 g, CoCl2 3,7 mg, FeSO4-H2O 5 mg,ZnSO4-H2O 1,4 mg; MnSO4-H2O 1,6 mg, glicose como fonte decarbono, sorbitol 182 g como estabilizante osmótico ehidgromicina 125 mg para a seleção. As placas foramsolidificadas e o crescimento das colônias foi restritoadicionando-se 2% de ágar 0,1% de Triton X-100 ao meio. Osprotoplastos transformados foram distribuídos em placas em ágarde superfície seletivo a 3% contendo IM sorbitol.

De modo a examinar a atividade da FAEA dediferentes transformantes, os fungos foram cultivados em meiomínimo contendo, por litro: (NH4)2SO4 5,0 g, KH2PO4 15,0 g,CaCl2 0,6 g, MgSO4 0,6 g, CoCl2 3,7 mg, FeSO4-H2O 5 mg,® ZnSO4-H2O 1,4 mg; MnS04.H20 1,6 mg, peptona 5 g e lactose 40g e celulose Solka floe (International Fiber Corporation, NorthTonawanda, NY) 20 g como fontes de carbono e indutores, Pipes33 g para ajustar o pH para 5.2 com KOH. O meio de cultura foiinoculado com IxlO esporos por 50 ml e cultivado em frascoscônicos a 30°C com agitação a 200 rpm.

Vetores de expressão e transformação fungica

A FAEA e SWOI de codificação do cDNAforam amplificadas por PCR a partir do plasmídeo pF (Record ecol. 2003) e, pMS89, incluindo o peptídeo de sinal, foiamplificado utilizando-se

tanto o iniciador direto Fl 5'-GATACCGCGGATGAAGCAATTCTCTGC -3 '(com o sítioSacII sublinhado)

quanto o iniciador F2 5'-GTGCAGTTTAGCAATGCCTCCACGCAAGGCATC -3 * e oiniciador reverso Rl 5'-

AAT ACAT ATGTTAGTGGTGGTGGTGGTGGTGCCAAGTACAAGCTCCGCTCG-3' (com o sítio NM sublinhado, His-tagsublinhado com pontos).

O primeiro par de iniciadores (Fl/Rl) foi usadopara obter um fragmento de DNA amplificado que será usado nocassete de expressão pFaeA para a expressão do gene decodificação da faeA (SEQ ID NO : 9) (Y09330) em T. reesei. Asegunda construção foi obtida fusionando o gene faeA ao gene(AK245918) codificando a SWOl (SEQ ID NO : 1) utilizando-seuma PCR de extensão por sobreposição (Ho e col. 1989). Noprimeiro experimento PCR, o gene faeA foi amplificado usando opar de iniciadores F2/R1 e o iniciador direto F3 5-ATATCCGCGGATGGCTGGTAAGCTTATC-3 ' (com o sítioSacII sublinhado) e o iniciador reverso R2 5'-GATGCCTTGCGTGGAGGCATTCTGGCTAAACTGCAC-3'.

Ambos os fragmentos sobrepostos resultantesforam misturados e um fragmento fiisionado foi sintetizadousando apenas iniciadores externos. Esse fragmento recém-obtidofoi clonado no cassete de expressão para expressar o gene defusão Swol-FaeA (pSwo-Faea).

Ambos os fragmentos amplificados foramverificados por sequenciamento, e então ligados no vetor deexpressão pAMHllO (sítios de clonagem, SacII e Ndei) apósdigestão com as enzimas de restrição SacII e NdeI. Neste vetor, opromotor do gene de codificação (cbhl) da celobiohidrolase I deT. reesei foi utilizado para conduzir a expressão de ambos osinsertos. No primeiro (pFaeA) e no segundo (pSwo-FaeA)cassetes de expressão, o peptídeo de sinal da FAEA e SWOl,respectivamente, foram usados para iniciar a secreção dasproteínas recombinantes.

A transformação fungica foi realizada comodescrito anteriormente (Penttila e col. 1987) utilizando-se osvetores de expressão. Os transformantes foram purificados pelaseleção de conídios no meio seletivo.

Separação da atividade da feruloil esterase

As culturas foram monitoradas por 10 dias a3O0C em uma incubadora agitadora e o pH foi ajustado para 5.5diariamente com um 1 M KOH. Cada condição de cultura foirealizada em duplicata. A partir do meio de cultura líquido,alíquotas (de 1 mL) foram coletadas diariamente, removendo osmicélios por filtração. A atividade da esterase foi analisada,conforme descrito anteriormente, usando ferulato de metila(MFA) como substrato (Ralet e col. 1994). As atividades foramexpressas em nkatal (nkat), com 1 nkat sendo definido como aquantidade de enzima que catalisa a liberação de 1 nmol de ácidosferúlicos por segundo sob condições estabelecidas. Cadaexperimento foi realizado em duplicata, e as medições emtriplicata. O desvio padrão foi registrado como menos de 2% paraa média.

Análise Protéica e Western blot

A concentração protéica foi determinada deacordo com Lowry et al. (1951) com soroalbumina bovina comopadrão. A purificação protéica foi seguida de eletroforese em gelde poliacrilamida-SDS em géis em placa de poliacrilamida a 10%(Laemli 1970). Em seguida, as proteínas foram coradas com azulCoomassie. A seqüência N-terminal foi determinada a partir deuma amostra de FAEA analisada por eletroblotting (40 μg) sobreuma membrana de poli(difluoreto de vinilidina) (Millipore, Saint-Quentin-Yvelines, França) segundo a degradação de Edman. Asanálises foram realizadas em um Applied Biosystem 470A.

Para a análise Western blot, as proteínas totais epurificadas foram submetidas à eletroforese em gel depoliacrilamida/SDS a 11% analisadas por "electroblotting" emmembranas de nitrocelulose BA85 (Schleicher e Schuell, Dassel,Alemanha) à temperatura ambiente durante 45 minutos. Asmembranas foram incubadas em solução de bloqueio (50 mM deTris, 150 mM de NaCl e 2% (v/v) de leite, pH 7,5) durante a noitea 4°C. Em seguida, as membranas foram lavadas com TBS a 0,2%Tween e tratadas com solução de bloqueio contendo soro anti-FAEA a uma diluição de 1/6000. Para anticorpos anti-FAEA, asmembranas foram subseqüentemente incubadas com anti-imunoglobina G de coelho produzido em cabra, conjugado comperoxidase alcalina (1/2500) (Promega). A fosfatase alcalina foirevelada a cores usando o ensaio do fosfato de 5-bromo-4-cloro-3-indoilo-azul de nitrotetrazólio (Roche Applied Science, Meylan,France) segundo o procedimento do fabricante.

Purificação e caracterização das proteínas

Para purificar ambas as proteínasrecombinantes, o melhor isolado para cada construção foiinoculado nas mesmas condições que o procedimento deseparação. A cultura foi coletada após 8 dias de crescimento,filtrada (0,7 μηι) e concentrada por ultrafiltração por meio de umamembrana de polietersulfona (corte de massa molecular de 30kDa) (Millipore). As frações concentradas foram dialisadas emum tampão de ligação de 30 mM de Tris-HCl, pH 7,0, e apurificação das proteínas marcadas com His foi realizada em umacoluna de Fluxo Rápido de Sefarose Quelante (13x15 cm)(Amersham Biosciences) (Porath e col. 1975).

As principais características enzimáticas foramdeterminadas para ambas as proteínas recombinantes. Atermoestabilidade das proteínas purificadas (100% refere-se a 4,3e 0,2 nanokatals ml"1 de FAEA e SWOI-FAEA, respectivamente)foi testada na faixa de 30 a 70°C. As alíquotas foram pré-incubadas na temperatura designada por 60 min e, apósresfriamento a 0°C, as atividades da esterase foram entãoanalisadas conforme indicado anteriormente, em condiçõespadrão. As amostras foram analisadas por SDS-PAGE após aincubação com o objetivo de verificar a integridade das proteínasrecombinantes. O efeito do pH sobre a estabilidade protéica foitambém estudado pela incubação, durante 60 minutos, dasproteínas recombinantes purificadas em tampão citrato-fosfato(pH 2,5 a 7,0) e fosfato de sódio (pH 7,0 a 8,0). Todas asincubações foram realizadas durante 90 minutos, e então asalíquotas foram transferidas em mistura reacional convencionalpara determinar a quantidade de atividade restante. A atividadedeterminada antes das pré-incubações foi de 100% (4,3 e 0,2nanokatals ml"1 de FAEA e FAES-SWO, respectivamente).

Para determinar a temperatura ideal sob ascondições utilizadas, alíquotas das proteínas recombinantespurificadas (100% refere-se a 4,3 e 0,2 nanokatals ml"1 de FAEAe SWEOI-FAEA, respectivamente) foram incubadas a váriastemperaturas (de 30 a 70°C) e as atividades da esterase foramanalisadas. O pH ideal foi determinado usando tampão citrato-fosfato (pH 2,5 a 7,0) e tampão fosfato de sódio (pH 7,0 a 8,0)usando condições padrão.

Análise Southern blot

O DNA genômico de cada um dostransformantes (10 μg) foi digerido durante a noite com váriasenzimas de restrição e submetido à eletroforese em um gel deagarose-TAE a 0,5%. O DNA foi então submetido ao "blotting"sobre uma membrana Hybond N+ e sondado com uma sondamarcada com P consistindo da seqüência amplificada por PCRfaeA. A hibridização foi realizada em um tampão contendofosfato de sódio a 0,5M pH7,2, EDTA a O5OlM, SDS a 7% (p/v),agente de bloqueio a 2% (p/v) (Roche Applied Science) durante anoite a 65°C. As lavagens pós-hibridização consistiram de 2 χ 15min em SSC a 0,2 (1 χ SSC é NaCl a 0,15 M mais tampão citratode sódio 0,015 M pH 7,0), contendo SDS a 1% a 65°C e 1 χ 5 minem 0,2 X SSC à temperatura ambiente. Os blots foram expostos aum filme radiográfico (Biomax MR, Eastman Kodak Company,Nova Iorque, EUA). A linhagem BRFM 281 de A. niger tiposelvagem (Banque de Ressources Fongique de Marseille) foiutilizada como controle contendo uma cópia do gene faeA.

Testes de aplicação

O farelo de trigo (WB) foi desamidado efornecido pela AED (Agro-industrie Recherche etDéveloppement, Pomacle, França). A hidrólise enzimática foirealizada em tampão ácido 3-(N-morfolino)propanosulfônico(MOPS) a 0,1 M contendo azida de sódio a 0,01% ao pH 6,0, emuma incubadora com agitação controlada termostaticamente (120rpm) a 37°C. O WB (180 mg) foi incubado com a FAEA, SWOI+ FAEA e SWOI-FAEA purificadas, de forma independente, emum volume final de 5 mL. Com respeito às aplicações de testecom meio de cultura dos transformantes, o volume final foiaumentado para 9 mL. As concentrações enzimáticas foram de 1,8nkatal de atividade da esterase por 180 mg de farelo seco paracada ensaio. Cada ensaio foi realizado em duplicata, e o desviopadrão foi menor do que 5% da média do valor para WB.Para estimarmos o teor de ácidohidroxicinâmico, o total extraível de álcali dos compostosfenólicos foi determinado pela adição de 20 mg de WB ou MBem NaOH a 2 N e incubada durante 30 minutos a 35 0C emescuridão. O pH foi ajustado para 2 com HCl a 2N. Os ácidosfenólicos foram extraídos três vezes com 3 ml de éter. A faseorgânica foi transferida para um tubo de ensaio e seca a 40°C.Um mililitro de metanol/H20 (50:50) (v/v) foi adicionado aoextrato seco e as amostras foram injetadas em um sistema HPLC,conforme descrito na próxima seção. O teor total de ácido ferúlicoextraível de álcali foi considerado como 100% para a hidróliseenzimática.

Finalmente, para determinarmos o teor de ácidoferúlico, os hidrolisatos enzimáticos foram diluídos a 1A comácido acético a 5%, centrifugados a 12.000 χ g durante 5 minutos,e os sobrenadantes foram filtrados através de um filtro de náilonde 0,2 μM (Gelman Sciences, Acrodisc 13, Ann Arbor, MI). Oslíquidos filtrados foram analisados por HPLC (25 μΣ, injetados).As análises HPLC foram efetuadas a 280 nm e 3O0C em ummodelo HPllOO (Hewlett-Packard Rockville, MD) equipado comum detector UV/VIS variável, um autoamostrador-autoinjetor de100 posições. As separações foram obtidas em uma coluna de faseinvertida Merck RPl8 (Chromolith 3,5 μηι, 4,6x100 mm, Merck).A vazão foi de 1,4 mL/min. A fase móvel usada foi ácido acéticoa 1% e acetonitrilo a 10% em água (A) versus acetonitrilo a 100%(B) durante um tempo de execução total de 20 minutos, e ogradiente se modificou como segue: o solvente B começou em0% durante 2 minutos, aumentando então para 50% em 10minutos, para 100% em 3 minutos até o final da execução. Osdados foram processados por uma HP 3365 ChemStation e aquantificação foi realizada por calibração externa padrão.

Exemplo 1: Transformação fungica e produçãodas enzimas recombinantes.

Duas linhagens de T. reesei, Rut-C30 e CL847,utilizadas por companhias industriais para produzir, em processosde fermentação controlada, uma grande quantidade de enzimas,foram transformadas pelos vetores de expressão contendo osgenes de interesse. Na primeira construção, o gene faeA de A.niger foi colocado sob controle do promotor do gene cbhl usandoo peptídeo de sinal da FAEA para direcionar a secreção. A FAEArecombinante foi utilizada nos seguintes testes de aplicação comocontrole. Na segunda construção, o gene faeA foi fusionado aogene de codificação de SwoI para produzir uma proteínaquimérica associando a FAEA de A. niger à proteína SWOI de T.reesei. Nesta construção, o peptídeo de sinal da SWOI foiutilizado para a secreção da proteína recombinante. Protoplastosobtidos de ambas as linhagens foram transformados de formaindependente por ambos os cassetes genéricos clonados no vetorde expressão pAMHllO. Os transformantes foram entãoselecionados pela sua capacidade de crescer em meio mínimocontendo higromicina. Aproximadamente trezentostransformantes foram adicionalmente purificados pela seleção deconídios em meio seletivo, e mais ou menos 150 colôniasresistentes à higromicina foram separadas detectando-se aatividade da feruloil esterase produzida no meio de cultura erealizando-se uma análise western blot. Considerando todos ostransformantes, somente uma atividade da feruloil foi detectávelpara aqueles transformados por pFaeA (transformantes FaeA).Além disso, a produção da FAEA foi confirmada pela análisewestern blot. Com respeito às colônias de T. reesei transformadaspor pSwo-FaeA (transformantes Swo-FaeA), uma produção deFAEA só foi detectada pela análise western blot, pois a atividadeda feruloil esterase teve pouquíssima produção. No entanto, paraos transformantes FaeA, 1,3 e 23,3% das colônias demonstraramproduzir uma atividade da feruloil esterase, respectivamente, paraas linhagens Rut-C30 e CL847. No segundo evento detransformação usando pSwo-FaeA, a porcentagem foi maior, com23,3 e 51,7% das colônias, respectivamente. Para cada construçãoe linhagem de T. reesei, os transformantes que apresentarammelhor produção foram então cultivados para estudarmos o cursode tempo da atividade da feruloil esterase.

A atividade da esterase foi estimada tanto emRut-C30 como em CL847 transformadas, que foramtransformadas por pFAEA, e relatada em função do tempo (Fig.1). Em ambos os casos, a atividade da esterase já era detectávelno segundo dia e aumentou progressivamente a 0,45 e 1,15 nkatal,respectivamente. Com respeito à T. reesei transformada porpSwo-FaeA, uma pequena atividade foi medida no oitavo dia, deaproximadamente 0,06 nkatal HiIZ1j para ambas as linhagens,análises Western blot foram realizadas a partir do meio de culturados transformantes FaeA (Fig. 2) e uma banda deaproximadamente 40 kDa correspondendo à FAEA recombinantefoi apresentada (Fig. 2, pistas 1 e 3). Além desse primeiroconjunto de transformantes fungicos, os transformantes Swo-FaeA produziram uma banda principal de aproximadamente 120kDa correspondendo à fusão da FAEA (36 kDa) e da proteínaSWOI (75 kDa) (Fig. 2, pistas 2 e 4). Além disso, apareceu umabanda fraca de 40 kDa, a qual corresponde ao tamanho da FAEA.Finalmente, o número de cópia dos cassetes de expressãointegrados no genoma fungico foi estimado pela análise Southernblot e revelou que os transformantes FaeA contêm de 4 a 5 e 9 a10 cópias, respectivamente, para as linhagens Rut-C30 e CL847.Com respeito ao conjunto de transformantes Swo-FaeA, foramestimadas 6 a 7 e 14 a 15 cópias para as duas linhagens,respectivamente. Uma vez que o T. reesei CL847 produz a mesma® quantidade de SWOI-FAEA que a linhagem Rut-C30, mas umrendimento maior de FAEA, os seguintes experimentos foramrealizados com as proteínas obtidas dessa linhagem.

Exemplo 2: Caracterização das enzimasrecombinantes

A FAEA purificada e a SWOI-FAEA quiméricaforam purificadas em uma coluna de Sefarose Quelante e ahomogeneidade das proteínas foi verificada em um gel deSDS/poliacrilamida (Fig. 3). A massa molecular da FAEArecombinante foi ligeiramente maior que a esperada, secomparado à FAEA produzida em A. niger. Ambas as seqüênciasN-terminais da FAEA (ASTQF) e da SWOI-FAEA (QQNCA)foram seqüenciadas, e foi constatado que elas são 100% idênticasàquelas das proteínas nativas correspondentes, demonstrando queo processamento foi correto. Todas as propriedades físico-químicas e cinéticas principais foram adicionalmentedeterminadas e comparadas com a FAEA de A. niger (Record ecol. 2003) (Tabela I e Fig. 4). Considerando o efeito datemperatura e do pH, bem como a estabilidade do pH, não foiencontrada nenhuma diferença significativa. A estabilidade detemperatura de ambas as proteínas também foi estimada e nossosresultados demonstraram que a FAEA recombinante foi estávelaté 45°C e que a atividade diminuiu em 60% após uma incubaçãode 60 min a 5 50C. Nenhuma atividade restante foi encontrada a60°C. Por outro lado, com respeito à proteína SWOI-FAEA, aatividade permaneceu estável até 40°C e nenhuma atividaderestante foi detectada após 60 minutos de incubação a 50°C. Nãofoi encontrada nenhuma diferença grande para o valor de Km.Entretanto, embora o Vm e as atividades específicas estivessemna mesma faixa para a FAEA produzida por A. niger e T. reesei,um claro desvio foi observado para a proteína SWOI-FAEA, quedemonstrou ser menos eficiente para hidrolisar o ferulato demetila do que a FAEA correspondente.

Exemplo 3: Liberação enzimática de ácidoferúlico a partir de farelo de trigoO efeito sinérgico gerado pela proximidadefísica da FAEA e da SWOI foi estudada para a liberação de ácidoferúlico a partir de farelo de trigo. O farelo de trigo foi incubadocom enzimas purificadas (Fig. 5), e os resultados mostraram que aFAEA produzida em A. niger e T. reesei foi capaz de liberara amesma quantidade de ácido ferúlico, isto é, de 6 a 9%,dependendo do tempo de incubação. Considerando a SWOI, aproteína nativa sozinha, ou em adição com a FAEA (S ou F+S)não foi eficiente se comparada com a referência ou experimentocom a FAEA, respectivamente. Por outro lado, um valorsignificativamente maior de liberação de ácido ferúlico, isto é, de7 a 13,5%, foi obtido com a proteína S WOI-FAEAcorrespondendo a um fator de aperfeiçoamento de 1,5 após 24horas de hidrólise.

A linhagem CL847 recombinante produzindo aSWOI-FAEA recombinante foi avaliada quanto à liberação deácido ferúlico usando o coquetel extracelular total dasenzimas segregadas. Embora o meio extracelular obtido dalinhagem parenteral não transformada fosse capaz deliberar 0,5 a 1,8% de ácido ferúlico de 4 a 24 horas deincubação, A linhagem CL847 transformada segregou umcoquetel enzimático incluindo a SWOI-FAEA que liberou até45% até 4 horas, isto é, 1,8 g de ácido ferúlico por kg de farelo detrigo. Esse rendimento não aumentou mesmo após 24 horas deincubação.Tabela 1: Características físico-químicas ecinéticas da feruloil esterase recombinante e da enzima quiméricade Trichoderma reesei.

<table>table see original document page 47</column></row><table>

aestimado a partir da esterase feruloil deAspergillus niger (Record e col. 2003)

bKm foram expressos em milimols

cVm foram expressos em nanokatal por mg deproteína

d as atividades específicas foram expressas emnanokatal por mg de proteína

As atividades foram analisadas utilizando-seferulato de metila como substrato.

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<110> INSTITUT FRANCAIS DU PETROLE

VTT TECHNICAL RESEARCH CENTRE OF FINLANDINSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE

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aca tcc gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg 480

Thr Ser Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser145 150 155 160

gcg gac tgc.aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc 528

Ala Asp Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser165 170 175

age aac gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg 576

Ser Asn Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu. Thr180 185 190

age ggc ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc 624

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly195 200 205

agt gtt aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac 672

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp 210 215 220

gct ttt tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act 720

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro. Thr Gly Thr225 230 235 240

acc ctt cgt ggc aac ttc gea gct cca. âac ggc gat tác tac acc caa 768

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln245 250 255

ttc tgg tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc 816

Phe Trp Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys,Gly260 265 270

gag tgc att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct 8 64

Glu Cys Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala·275 280 285

gtc gga gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac 912

Val Gly Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp290 ' 295 300

age tgc ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc 960 .

Ser Cys Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala305 310 315 320

gat cat tgc. gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct 1008

Asp His Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala325 330 335

gac age att cat ctc gac.ctg tca gac att gcc atg ggc·cgt ttg cag 1056

Asp Ser Ile His Leu Asp.Leu Ser Asp Ile Ala Met Gly Arg Leu Gln340 345 350

ggc aat gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga 1104

Gly Asn Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg355 360 365

gtc caa tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc 1152Val Gln Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly370 375 380

gga 'ggg cct tac tat ttt gct ctc acg gca gtc aac acc aac gga ccg 1200

Gly Gly Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro385 390 395 400

ggc tca gtc acc aaa. ate gag ate aag ggc gca gac acc gac aac tgg 1248

Gly Ser Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp405 410 .415

gtt gcc ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa 1296Val Ala Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu420 425 430

cgc tat ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg 134 4

Arg Tyr Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu435 440 . 445

cct gtt gga att cgt ctg act age cca acg ggg gaa cag att gtg aat 13'92

Pro Val Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn450 455 460

gaa cag gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat 14 40Glu Gln Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn465 470 475 480

1479

ttt tac tac att gac att ggt gtg cag ttt age cag aatPhe Tyr Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn 485 490

<210> 2 <211> 493 <212> PRT <213> Trichoderma reesei < 4 0 0 > 2

Met Ala Gly Lys Leu Ile Leu Val Ala Leu Ala Ser Leu Val Ser Leu1 5 10 15

Ser Ile Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile20 25 30

Gly Trp Ser GlyThr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe35 4 0 4 5

Val Asn Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro50 55 60

Pro Asn Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala65 70 75 80

Ser Ser Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly85 90 95Ser Ala Ser Thr Tyr Thr Thr Thr Asp Thr. Ala Thr Val Ala Pro His100 105 110

Ser Gln Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp115 120 125

Thr Leu Val Asp Asn Val Cys-Cys Pro Ser Tyr Cys Ala Asn Asp Asp130 135 140

Thr Ser Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser145 150 155 160

Ala Asp Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser165 170 175

Ser Asn Glu Ser .Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr180 185 190

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly195 200 205

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp210 215 220

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr225 230 235 240

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln245 250 255

Phe Trp Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly260 265 270

Glu Cys Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala275 280 285

Val Gly Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp290 295 300

Ser Cys Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala305 310 315 320

Asp His Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala325 330 335Asp Ser Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln340 345 350

Gly Asn Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg355 360 365

Val Gln Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly370 375 380

Gly Gly Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro385 390 395 4Ό0

Gly Ser Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp405 410 415

Val Ala Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu420 425 430

Arg Tyr Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu435 440 445

Pro Val Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn450 455 460

Glu Gln Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn465 470 475 480

Phe Tyr Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn485 490

<210> 3

<211> 1425

<212> DNA

<213> Trichoderma reesei

<220>

<221> CDS<222> (1)..(1425)

<400> 3

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

96

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 144li

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro. Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gea tcc tca 192

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag 288

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc age att gcc gea tcc agt tgc gga tcg tgg acc ctc 33 6

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 .120 125

gag tca tgc tca ggc ^tgc ggt acc tgc act acg ccg ccc tcg gcg gac 432

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 4 80

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn14.5 150 "'155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age "ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His^ Phe Gly Leu Thr Ser Gly165 170 ■■■■■·■ 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 57 6

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Glv Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt .gac gct ttt 624

Thr Ala Ser Trpi Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgcGlu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys

864275

280

285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat catPro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

912

tgc gga gag ate gac .ttc aaa tac ggc tgt cct ctt cct gct gac ageCys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

960

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aatIle His Leu Asp Leu Ser Asp Ile Ala Met. Gly Arg Leu Gln Gly Asn325 330 335

1008

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc câaGly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

1056

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga gggCys Pro Lys Val Gly Asn Ala Tyr Ile ^Trp Leu Arg Asn Gly Gly Gly355 360 365

1104

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tcaPro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

1152

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gccVal Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

1200

ttg gtc cat gac cca aac tat acg agt age cgc cça caa gaa cgc tatLeu Val His Asp Pro Asn Tyr -Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

1248

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gttGly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

1296

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cagGly Ile Arg Leu Thr Ser Pro Thr Gly'Glu Gln Ile Val Asn Glu Gln435 440 445"

1344

gcc ate aag aca ttc act cct ccg gcc aca .ggt gac ccc aat ttt tacAla Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

1392

tac att gac att ggt gtg cag ttt àgc cag aatTyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn465 470 475

1425

<210> 4

<211> 475

<212> PRT

<213> Triehoderma reesei

<4 00>

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asri20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 . 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asj260 265

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu IIe275 280

Tyr Ala Val Gly270

Val Asp Ser Cys285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Prq Gly Ala Asp His290 295 30u

Cys Gly Glu Ile Asp Phe Lys. Tyr Gly Cys Pro LediPro Ala Asp Ser305 310. 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arçj325 330

Gly Ser Leu Thr Asn Gly'Val Ile Pro Thr Arg Tyr 340 345

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg355 360

Leu Gln Gly Asn 335

Arg Arg Val Gln350

Asn Gly Gly Gly365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr AsrijGly Pro Gly Ser370 375 380

Val Thr Lys IleGluIle Lys Gly Ala Asp Thr Asp385 390 395

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Proi405 410

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe420 425

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ilel435 440 Ij

Asn Trp Val Ala400

Gln Glu Arg Tyr 415

Asn Leu Pro Val430

Val Asn Glu Gln445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly AspijPro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn465 470 475

<210> 5

<211> 1503

<212> DNA

<213> Aspergillus fumigatus<220>

<221> CDS<222> (1)..(1503)

<4 00> 5

atg act ctt cta ttt ggt ata ttt ctt gcc cgg ctt gcg gtg gct gcc 48

Met Thr Leu Leu Phe Gly Ile Phe Leu Ala Arg Leu Ala Val Ala Ala1 5 10 15

gcc cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet 96

Ala Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser

20 25 30

tat acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att 14 4

Tyr Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile

35 40 45

aac tcg tac tac tac cag tgc ata cca gea aca gct gtg. agt act tca 192

m-

mmps-5

ι»

m

Ste

Asn Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser

m: 50 55 60

act acc aca gtg -aca tet ccc tet age tet ggt tcg tet tet gcc aac 240

Thr Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn65 70 75 80

acg tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca 288

Thr Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro' Thr Ala Thr85 90 95

cag aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct 336

Gln Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala

100 105 110

ctc gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa 384

Leu Va.l Asp Asri Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu115 120 125

tcc gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat 432

Ser Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp130 1 135 140

tcc tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta 480

Ser Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val145 150 155 160

act tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg 528

Thr Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu165 170 175

acc age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag 576

Thr Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys180 185 190

aac agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc 624

Asn Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys195 200 205

gac gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac 672

Asp Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn210 215 220gtc act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act 720

Val Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr

225 230 235 240

cag ttc tgg cct tcc ctg gct gca tcc ggc aat ccc gac aac tac ctc 7 68

Gln Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu

245 250 255

tct tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca 816

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

260 265 270

gac tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag 8 64

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

275 280 285

gta gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag 912

Val Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys

290 295 300

cgg ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat 960

Arg Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn

305 310 315 320

ctc aca aga cca ggc ggc age ggc gca gac cac tgc ggc gaa ate gac 1008

Leu Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp

325 330 335

ttc aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc 1056

Phe Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu340 345 350

tcc gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac 1104

Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp355 360 365

ggt gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg·ggg 1152

Gly Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly

370 375 380

aac ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg 1200

Asn Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala

385 390 395 400

ctg age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa 1248

Leu Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu

405 410 415

gtc cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg 1296

Val Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro

420 425 430

aac tac acc agt age cgg ccg cag gag cgg tat ggc tct tgg gtc ctc 134 4

Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu

435 440 445

ccg cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg 1392

Pro Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr

450 455 460gcg ccc aat ggg cag cag gtg gtt aagAla Pro Asn Gly Gln Gln Val Val Lys465 470 475 480

acc ccg ccg gcg act gcg gtc gag ggcThr Pro Pro Ala Thr Ala Val Glu Gly485 490 495

gtg cag ttc acc tagVal Gln Phe Thr500

<210> 6

<211> 500

<212> PRT

<213> Aspergillus fumigatus

<400> 6

Met Thr Leu Leu Phe Gly Ile Phe Leu Ala Arg Leu Ala Val Ala Ala1 5 10 15

Ala Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser20 25 30

Tyr Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile35 40 45

Asn Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser50 55 60

Thr Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn65 70 75 80

Thr Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr'85 90 95

Gln Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala100 105 110

Leu Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu115 120 125

Ser Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp130 ·. 135 140

Ser.Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val145 150 155 160

Thr Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu165

170

175

Thr Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys180 185 190

Asn Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys195 200 205

Asp Ala Phe Cys Thr Ala Tyr Pro Leu Leu. Cys Lys Asp Pro Ala Asn210 215 220

Val Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr225 230 235 240

Gln Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Piro Asp Asn Tyr Leu245 250 255

Ser Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr260 265 270

Asp Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu275 280 285

Val Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys290 295 300

Arg Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn305 310 315 320

Leu Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp325 330 335

Phe Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu340 345 350

Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp355 360 365

Gly Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly370 375 380

Asn Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala385 390 395 400

Leu Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu405 410 415Val Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro420 425 430

Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu435 440 445

Pro Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr450 455 460

Ala Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr465 470 475 480

Thr Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly

485 490 495

Val Gln Phe Thr500

<210> 7

<211> 1449

<212> DNA

<213> Aspergillus fumigatus

<220>

<221> . CDS<222> (1)..(1449)

<4 00> 7

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat 4 8

Gln Ser Ser .Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr

1 5 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac 96

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca act 14 4

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acg 192

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cag 240

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct etc 288

Asn Pro Tyr -Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 4 32Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 4 80Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg' aca gac cca atg ctg ggc tet acc tgc gac 576Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672Thr Leu Arg Gly Asn.Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gea tcc ggc aat ccc gac aac tac ctc tet 720Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816Tyr Ala Vai Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 8 64Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaa ate gac ttc 960Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 . 3.20

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gce gac ggt 1056Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly ,340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pró Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 1344

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr lie. Asp Leu Gly Val465 470 475 480

cag ttc acc 1449

Gln Phe Thr

<210> 8

<211> 483

<212> PRT

<213> Aspergillus fumigatus

<400> 8

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125.

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr;Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300ThrArg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser. Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr

<210> 9

<211> 780

<212> DNA

<213> Aspergillus niger

<220>

<221> CDS

<222> (1)..(780)

<400> 9

gcc tcc acg caa ggc ate tcc gaa gac ctc tac aat cgc ttg gta gagAla Ser Thr Gln Gly Ile Ser Glu Asp Leu Tyr Asn Arg Leu Val Glu 1 5 10 15

atg gcc act ate tcc caa gcc gcc tac gcc gac cta tgc aat att cca 96

Met Ala Thr Ile Ser Gln Ala Ala Tyr Ala Asp Leu Cys Asn Ile Pro20 25 30

tcg act att ate aaa gga gag aaa att tac aac gct caa act gat ate 144

Ser Thr Ile Ile Lys Gly Glu Lys Ile Tyr Asn Ala Gln Thr Asp Ile35 40 45

aac gga tgg ate etc cgc gac gac acc age aaa gaa att ate acc gtc 192

Asn Gly Trp Ile Leu Arg Asp Asp Thr Ser Lys Glu Ile Ile Thr Val50 55 60

ttc cgt ggc act ggc agt gac aca aac cta cag ctc gat act aac tac 240

Phe Arg Gly Thr Gly Ser Asp Thr Asn Leu Gln Leu Asp Thr Asn Tyr65 70 75 80

acg etc acg cca ttc gac act cta cct caa tgc aac gat tgc gag gta 288

Thr Leu Thr Pro Phe Asp Thr Leu Pro Gln Cys Asn Asp Cys Glu Val85 90 95

cac ggt gga tac tat att gga tgg ate tca gtc caa gac caa gtc gag 33 6

His Gly Gly Tyr Tyr Ile Gly Trp Ile Se.r Val Gln. Asp Gln Val Glu100 105 110

tcg ctt gtc aaa caa cag gct age cag tat ccg gac tat gcg ctt acc 384

Ser Leu Val Lys Gln Gln Ala Ser Gln Tyr Pro Asp Tyr Ala Leu Thr115 120 125

gtg aca ggc cat agt ctg gga gcg tcg atg gea gea ctc act gcc gcc 4 32

Val -Thr Gly His Ser Leu Gly Ala Ser Met Ala Ala Leu Thr Ala Ala130 135 140

cag ctg tcc gcg aca tac gac aac·gtc cgt çtg tac aca ttc ggc gaa 480

Gln Leu Ser Ala Thr Tyr Asp Asn Val Arg Leu Tyr Thr Phe Gly Glu145 150 · 155 160

ccg cgc age ggc aac cag gcc ttc gcg tcg tac atg aac gat gcg ttc 528

Pro Arg Ser Gly Asn Gln Ala Phe Ala Ser Tyr Met Asn Asp Ala Phe165 170 175

cag gtc tcg age ccg gag acg acc cag tac ttc cgg gtc act cat tcc 576

Gln Val Ser Ser Pro Glu Thr Thr Gln Tyr Phe Arg Val Thr His Ser180 185 190

aac gac ggc ate cca aac ttg ccc ccg gcg gac gag ggt tac gcc cat 624

Asn Asp Gly Ile Pro Asn Leu Pro Pro Ala Asp Glu Gly Tyr Ala. His195 200 205

ggt ggt gta gag tac tgg age gtt gat cct tac age gcc cag aac acg 672

Gly Gly Val Glu Tyr Trp Ser Val Asp Pro Tyr Ser Ala Gln Asn Thr210 215 220

ttt gtc tgt act ggg gat gaa gta cag tgc tgt gag gea cag ggc gga 720

Phe Val Cys Thr Gly Asp.Glu Val Gln Cys Cys Glu Ala Gln Gly Gly225 230 235 240

cag ggg gtg aat gat gcg cat act act tat ttt ggg atg acg age gga 768

Gln Gly Val Asn Asp Ala His Thr Thr Tyr Phe Gly Met Thr Ser Gly245

250

255

gct tgt act tggAla Cys Thr Trp260

780

<210> 10<211> 260<212> PRT<213> Aspergillus niger<4 00> 10Ala Ser Thr Gln Gly Ile Ser

10 15

Met Ala Thr Ile Ser Gln Ala Ala Tyr Ala Asp Leu Cys Asn Ile Pro20 25 30

Ser Thr Ile Ile Lys Gly Glu Lys Ile Tyr Asn Ala Gln Thr Asp Ile35 40 45

Asn Gly Trp Ile Leu Arg Asp Asp Thr Sér Lys Glu Ile Ile Thr Val50 55 60

Phe Arg Gly Thr .Gly Ser Asp Thr Asn Leu Gln Leu Asp Thr Asn Tyr65 70 75 80

Thr Leu Thr Pro, Phe Asp Thr Leu Pro Gln Cys Asn Asp Cys Glu Val85 90 95

His Gly Gly Tyr Tyr Ile Gly Trp Ile Ser Val Gln Asp Gln Val GluIOO1 105 110

Ser Leu Val Lys. Gln Gln Ala Ser Gln Tyr Pro Asp Tyr Ala Leu Thr115 120 125

Val Thr Gly His Ser Leu Gly Ala Ser Met Ala Ala Leu Thr Ala Ala130 13-5 140

Gln Leu Ser Ala Thr Tyr, Asp Asn Val Arg Leu Tyr Thr Phe Gly Glu145 150 155 160

Pro Arg Ser Gly Asn Gln Ala Phe Ala Ser Tyr Met Asn Asp Ala Phe165 170 175

Gln Val Ser Ser Pro Glu Thr Thr Gln Tyr Phe Arg Val Thr His Ser180 185 190Asn Asp Gly Ile Pro Asn Leu Pro Pro Ala Asp Glu Gly Tyr Ala His195 200 205

Gly Gly Val Glu Tyr Trp Ser Val Asp Pro Tyr Ser Ala Gln Asn Thr210 215 220

Phe Val Cys Thr Gly Asp Glu Val Gln Cys Cys Glu Ala Gln Gly Gly225 230 235 240

Gln Gly Val Asn Asp Ala His Thr Thr Tyr Phe Gly Met Thr Ser Gly245 250 255

Ala Cys Thr Trp260

<210> 11

<2Í1> 1512

<212> DNA

<213> Aspergillus niger

<220>

<221> CDS<222> (1)..(1512)

<400> 11

gcg acc gac ccc ttc cag tcg cgg tgc aat gaa ttc cag aac aag ate 4 8

Ala Thr Asp Pro Phe Gln Ser Arg Cys Asn Glu Phe GlnAsn Lys Ile1 5 10 15

gac ate gcc aat gtc acc gtc aga tcg gtc gea tac gtt gct gct gga 96

Asp Ile Ala Asn Val Thr Val Arg Ser Val Ala Tyr Val Ala Ala Gly20 25 30

cag aac ate tcc caa gcg gag gtc gcc tcc gtg tgt aaa gea tcg gtt 14 4

Gln Asn Ile Ser Gln Ala Glu Val Ala Ser Val Cys Lys Ala Ser Val35 40 45

caa gcc agt gtc gac ctg tgc cgg gta acc atg aac ate tcg acg tcg 192Gln Ala Ser Val Asp Leu Cys Arg Vâl Thr Met Asn Ile Ser Thr Ser50 55 60

gat cgc age cat ctg tgg gct gag gcc tgg ctc cca aga aat tat acc 240

Asp Arg Ser His Leu Trp Ala Glu Ala Trp Leu Pro Arg Asn Tyr Thr65 70 75 80

ggt cgc- ttc gtg age acg ggg aat gga ggt cta gcc ggc tgt gtc caa 288

Gly Arg Phe Val Ser Thr Gly Asn Gly Gly Leu Ala Gly Cys Val Gln8 5 90 95

gaa acg gac ctc aac ttt gea gcc aac ttt ggt ttc gct acc gtg ggc 336

Glu Thr Asp Leu Asn Phe Ala Ala Asn Phe Gly Phe Ala Thr Val Gly100 105 110

acc aac ggt gga cat gac ggg gac acg gcc aaa tac ttc ctc aac aac

384Thr Asn Gly Gly His Asp Gly Asp Thr115 120

tcg gag gtt ctg gcc gat ttt gcc tatSer Glu Val Leu Ala Asp Phe Ala Tyr130 135

Ala Lys Tyr Phe Leu Asn Asn125

cgc tca gtg cac gaa ggg acc 432

Arg Ser Val His Glu Gly Thr140

gtg gtg ggt aag caa cta act caa ttg ttt tat gac gag gga tac aac 480

Val Val Gly Lys Gln Leu Thr Gln Leu Phe Tyr Asp Glu Gly Tyr Asn145 150 155 160

tac tcc tac tat ttg ggt tgc tcc acc gga ggc cgc caa ggc tac cag 528

Tyr Ser Tyr Tyr Leu Gly Cys Ser Thr Gly Gly Arg Gln Gly Tyr Gln165 170 175

caa gtc caa cgg ttt ccc gac gac tat gac gga gtg att gcg ggc tcc 576

Gln Val Gln Arg Phe Pro Asp Asp Tyr Asp Gly Val Ile Ala Gly Ser180 185 190

gca gcg atg aa,c ttt ate aac ctg ate tcc tgg ggg gcc ttc ttg tgg 624

Ala Ala Met Asn Phe Ile Asn Leu Ile Ser Trp Gly Ala Phe Leu Trp195 200 205

aag gcg acg gg.g tta gcg gat gat cca gac ttt ate tet gca. aac ctg 672

Lys Ala Thr Gly Leu Ala Asp Asp Pro Asp Phe Ile Ser Ala Asn Leu210 215 220

tgg tcc gta ate cac cag gag att gtt cgt cag tgc gac ctg gtc gat 720

Trp Ser Val Ile His Gln Glu Ile Val Arg Gln Cys Asp Leu Val Asp225 230 235 240

ggg gct ctg gat gga ate ate gaa gac cct gat ttc tgt gct cca gtc 7 68

Gly Ala Leu Asp Gly Ile Ile Glu Asp Pro Asp Phe Cys Ala Pro Val245 250 255

ate gag cgc ttg ate tgc gac ggg act acc aac ggc acc tet tgt ate 816

Ile Glu Arg Leu Ile Cys Asp Gly Thr Thr Asn Gly Thr Ser Cys Ile260 265 270

acg gga gcc cag gca gca aag gtc aac cgg gcc- ttg agt gac ttc tat 8 64

Thr Gly Ala Gln Ala Ala Lys Val Asn Arg Ala Leu Ser Asp Phe Tyr275 280 285

ggc ccc gac ggg aca gtg tac tac ccg cgc ctg aac tat ggg ggt gag 912

Gly Pro Asp Gly Thr Val Tyr Tyr Pro Arg Leu Asn Tyr Gly Gly Glu290 295 300

gcc gac tcg gct tcc ctg tac ttc acg ggg tcg atg tac age cgt acg 960

Ala Asp Ser Ala Ser Leu Tyr Phe Thr Gly Ser Met- Tyr Ser Arg Thr305 310 315 320

gag gaa tgg tac aaa tat gtg gtc tat aac gac acc aac tgg aac tcc 1008

Glu Glu Trp Tyr Lys Tyr Val Val Tyr Asn Asp Thr Asn Trp Asn Ser325 330 335

age cag tgg acg ctg gag agt gcc aag ctg gcc ctg gag cag aat ccg 1056

Ser Gln Trp Thr Leu Glu Ser Ala Lys Leu Ala Leu Glu Gln Asn Pro340 345 350

ttc aat ate cag gcg ttt gat ccc aac ate acg gcc ttc cgg gac cgg 1104

Phe Asn Ile Gln Ala Phe Asp Pro Asn Ile Thr Ala Phe Arg Asp Arg355 360 365

ggt ggc aag ctg ctg tcc tac cac ggc acg'cag gat ccc att ate age 1152

Gly Gly Lys Leu Leu Ser Tyr His Gly Thr Gln Asp Pro Ile Ile Ser370 375 380

tcc acg gat age aag ctc tac tac cga cgg gta gcg aat gcc ctg aat 1200

Ser Thr Asp Ser Lys Leu Tyr Tyr Arg Arg Val Ala Asn Ala Leu Asn385 390 395 400

gcc gcg ccg tcc gag cta gat gag ttc tat cgg ttc ttc cag ate tcc 1248

Ala Ala Pro Ser Glu Leu Asp Glu Phe Tyr Arg Phe Phe Gln Ile Ser405 410 415

ggc atg ggc cac tgt ggc gat ggc acg gga gea tcg tac ate ggc cag 1296

Gly Met Gly His Cys Gly Asp Gly Thr Gly Ala Ser Tyr Ile Gly Gln-420 425 430

gga tat ggc acg tac acc tcc aag gcg ccc caa gtc aac ctg ctg cgc 134 4

Gly Tyr Gly Thr Tyr Thr Ser Lys Ala Pro Gln Val Asn Leu Leu Arg435 440 445

acg atg gtg gac tgg gtg gaa aac gga aag gcg ccc gag tat atg ccg 1392Thr Met Val Asp Trp Val Glu Asn Gly Lys Ala Pro Glu Tyr Met Pro450 455 460

ggc aac aag ctc aac gcg aac ggg tca att gag tac atg cgc aag cac 1440

Gly Asn Lys Leu Asn Ala Asn Gly Ser Ile Glu Tyr Met Arg Lys His465 470 475 480

tgc cgg tat ccg aag cat aac att cac acg ggg ccg ggt aac tac acc 1488

Cys Arg Tyr Pro Lys His Asn Ile His Thr Gly Pro Gly Asn Tyr Thr485 490 495

gat cct aac tcc·tgg act tgc gta 1512

Asp Pro Asn Ser Trp Thr Cys Val500

<210> 12

<211> 504

<212> PRT

<213> Aspergillus niger

<400> 12

Ala Thr Asp Pro Phe Gln Ser Arg Cys Asn Glu Phe Gln Asn Lys Ile1 5 10 15

Asp Ile Ala Asn Val Thr Val Arg Ser Val Ala Tyr Val Ala Ala Gly20 25 30

Gln Asn Ile Ser Gln Ala Glu Val Ala Ser Val Cys Lys. Ala Ser Val35 40 45

Gln Ala Ser Val Asp Leu Cys Arg Val Thr Met Asn Ile Ser Thr Ser50 55 60Asp Arg Ser His Leu Trp Ala Glu Ala Trp Leu Pro Arg Asn Tyr Thr65 70 75 80

Gly Arg Phe Val Ser Thr Gly Asn Gly Gly Leu Ala Gly Cys Val Gln85 90 95

Glu Thr Asp Leu Asn Phe Ala Ala Asn Phe Gly Phe Ala Thr Val Gly100 105 110

Thr Asn Gly Gly His Asp Gly Asp Thr Ala Lys Tyr Phe Leu Asn Asn115 120 125

Ser Glu Val Leu Ala Asp Phe Ala Tyr Arg Ser Val His Glu Gly Thr130 135 140

Val Val Gly Lys Gln Leu Thr Gln Leu Phe Tyr Asp Glu Gly Tyr Asn145 150 155 160

Tyr Ser Tyr Tyr Leu Gly Cys Ser Thr Gly Gly Arg Gln Gly Tyr Gln165 170 175

Gln Val Gln Arg Phe Pro Asp Asp Tyr Asp Gly Val Ile Ala Gly Ser180 185 190

Ala Ala Met Asn Phe Ile Asn Leu Ile Ser Trp Gly Ala Phe Leu Trp195 200 205

Lys Ala Thr Gly Leu Ala Asp Asp Pro Asp Phe Ile Ser Ala Asn Leu210 215 220

Trp Ser Val Ile His Gln Glu He -Val Arg Gln Cys Asp Leu Val Asp225 230 235 240

Gly Ala Leu Asp Gly Ile Ile Glu Asp Pro Asp Phe Cys Ala Pro Val245 250 255

Ile Glu Arg Leu Ile Cys Asp Gly Thr Thr Asn Gly Thr Ser Cys Ile260 265 270

Thr Gly Ala Gln Ala Ala Lys Val Asn Arg Ala Leu Ser Asp Phe Tyr275 280 285

Gly Pro Asp Gly Thr Val Tyr Tyr Pro Arg Leu Asn Tyr Gly Gly Glu290 295 300Ala Asp Ser Ala. Ser Leu Tyr Phe Thr Gly Ser Met Tyr Ser Arg Thr305 310 315 320

Glu Glu Trp Tyr Lys Tyr Val Val Tyr Asn Asp Thr Asn Trp Asn Ser325 330 335

Ser Gln Trp Thr Leu Glu Ser Ala Lys Leu Ala Leu Glu Gln Asn Pro340 345 350

Phe. Asn Ile Gln Ala Phe Asp Pro Asn Ile Thr Ala Phe Arg Asp Arg355 360 365

Gly Gly Lys Leu Leu Ser Tyr His Gly Thr Gln Asp Pro Ile Ile Ser370 375 380

Ser Thr Asp Ser Lys Leu Tyr Tyr Arg Arg Val Ala Asn Ala Leu Asn385 390 ' 395 . 400

Ala Ala Pro Ser Glu Leu Asp Glu Phe Tyr Arg Phe Phe Gln Ile Ser405 410 415

Gly Met Gly His Cys Gly Asp Gly Thr Gly Ala Ser Tyr Ile Gly Gln420 425 430

Gly Tyr Gly Thr Tyr Thr Ser Lys Ala Pro Gln Val Asn Leu Leu Arg435 440 445

Thr Met Val Asp Trp Val Glu Asn Gly Lys Ala Pro Glu Tyr Met Pro450 455 460

Gly Asn Lys Leu Asn Ala Asn Gly Ser Ile Glu Tyr Met Arg Lys His465 470' 475 480

Cys Arg Tyr Pro Lys His Asn Ile His Thr Gly Pro Gly Asn Tyr Thr485 490 495

Asp Pro Asn Ser Trp Thr Cys Val500

<210> 13

<211> 564

<212> DNA

<213> Aspergillus niger

<220>

<221> CDS<222> (1) . . (564)<400> 13

tcg acc ccg age tcg acc ggc gag aac aac ggc ttc tac tac tcc ttc 48

S-er Thr Pro Ser Ser Thr Gly Glu Asn Asn Gly Phe Tyr Tyr Ser Phe1 5 10 15

tgg acc gac ggc ggt gga gac gtg acc tac acc aac gga gat gct ggt 96

Trp Thr Asp Gly Gly Gly Asp Val Thr Tyr Thr Asn Gly Asp Ala Gly20 25 30

gcc tac act gtt gag tgg t.cc aac gtg ggc aac ttt gtc ggt gga aag 144

Ala- Tyr Thr Val Glu Trp Ser Asn Val Gly Asn Phe Val Gly Gly Lys35 40 45

ggc tgg aac ccc gga agt gcg cag gac ate acc tac age ggc acc ttc 192

Gly Trp Asn Pro Gly Ser Ala Gln Asp Ile Thr Tyr Ser Gly Thr Phe50 55 60

acc cct age ggc aac ggc tac ctc tcc gtc tat ggc tgg acc act gac 240

Thr Pro Ser Gly Asn Gly Tyr Leu Ser Val Tyr Gly Trp Thr Thr Asp65 70 75 80

cct ctg ate gag tac tac ate gtc gag tet tac ggc gac tac aac ccc 288

Pro Leu Ile Glu Tyr. Tyr Ile Val Glu Ser Tyr Gly Asp Tyr Asn Pro85 90 95

ggc agt gga ggc acg tac aag ggc acc gtc acc tcg gac gga tcc gtt 336

Gly Ser Gly Gly Thr Tyr Lys Gly Thr Val Thr Ser Asp Gly Ser Val100 105 110

tac gat ate tac acg gct acc cgt acc aat gct gct tcc att cag gga 384

Tyr Asp Ile Tyr Thr Ala Thr Arg Thr Asn Ala Ala Ser Ile Gln Gly115 120 125

acc gct acc. ttc act cag tac tgg tcc gtt cgc cag aac aag aga gtt 432

Thr Ala Thr Phe Thr Gln Tyr Trp Ser Val Arg Gln Asn Lys Arg Val130 135 140

ggc gga acc gtt acc acc tcc aac cac ttc aat gct tgg gct aag ctg 480

Gly Gly Thr Vali Thr Thr Ser Asn His Phe Asn Ala Trp Ala Lys Leu145 150 155 160

gga atg aac ctg ggt act cac aac tac cag ate gtg gct acc gag ggt 528

Gly Met Asn Leu Gly Thr His Asn Tyr Gln Ile Val Ala Thr Glu Gly165 170 175

tac cag age agt gga tet tcg tcc ate act gtt cag 564

Tyr Gln Ser Ser Gly Ser Ser Ser Ile Thr Val Gln180 185

<210> 14 <211> 188 <212> PRT <213> Aspergillus niger <400> 14

Ser Thr Pro Ser Ser Thr Gly Glu Asn Asn Gly Phe Tyr Tyr Ser1 5 10 15Trp Thr Asp Gly Gly Gly Asp Val Thr Tyr Thr Asn Gly Asp Ala Gly20 25 30

Ala Tyr Thr Val Glu Trp Ser Asn Val Gly Asn Phe Val Gly Gly Lys35 40 45

Gly Trp Asn Pro Gly Ser Ala Gln Asp Ile Thr Tyr Ser Gly Thr Phe50 55 60

Thr Pro Ser Gly Asn Gly Tyr Leu Ser Val Tyr Gly Trp Thr Thr Asp65 70 75 80

Pro Leu Ile Glu Tyr Tyr Ile Val Glu Ser Tyr Gly Asp Tyr Asn Pro85 90 95

Gly Ser Gly Gly Thr Tyr Lys Gly Thr Val Thr Ser Asp Gly Ser Val100 105 110

Tyr Asp Ile Tyr Thr Ala Thr Arg Thr Asn Ala Ala Ser Ile Gln Gly115 120 125

Thr Ala Thr Phe Thr Gln Tyr Trp Ser Val Arg Gln Asn Lys Arg Val130 135 140

Gly Gly Thr Val Thr Thr Ser Asn His Phe Asn Ala Trp Ala Lys Leu145 150 155 160

Gly Met Asn Leu Gly Thr His Asn Tyr Gln Ile Val Ala Thr Glu Gly165 170 175

Tyr Gln Ser Ser Gly Ser Ser Ser Ile Thr Val Gln180 185

<210> 15

<211> 1494

<212> DNA

<213> Trichoderma reesei

<220>

<221> CDS

<222> (1)..(1494)

<400> 15

cag tcg gcc tgc act ctc caa tcg gag act cac ccg cct ctg aca tggGln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro Leu Thr Trp15 10 15

cag aaa tgc tcg tct ggt ggc acg tgc act caa cag aca ggc tcc gtgGln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser Val20 25 30

gtc ate gac gcc aac tgg cgc tgg act cac gct acg aac age age acg 14 4

Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn Ser Ser Thr35 40 45

aac tgc tac gat ggc aac act tgg age tcg acc cta tgt cct gac aac 192

Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp Asn50 55 60

gag acc tgc gcg aag aac tgc tgt ctg gac ggt gcc gcc tac gcg tcc 240

Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala Ser65 70 75 80

acg tac gga gtt acc acg age ggt aac age etc tcc att ggc ttt gtc 288

Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe Val85 90 95

acc cag tet gcg cag aag aac gtt ggc gct cgc ctt tac ctt atg gcg 336

Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr Leu Met Ala100 105 110

age gac acg acc tac cag gaa ttc acc ctg ctt ggc aac gag ttc tet 384

Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe Ser115 120 125

ttc gat gtt gat gtt tcg cag ctg ccg tgc ggc ttg .aac gga gct ctc 4 32

Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala Leu 130 135 140

tac ttc gtg tcc atg gac gcg gat ggt ggc gtg age aag tat ccc acc 480

Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro Thr145 150 155 160

aac acc gct ggc gcc aag tac ggc acg ggg t.ac tgt gac age cag tgt 528

Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln Cys165 170 175

ccc cgc gat ctg aag ttc ate aat ggc cag gcc aac gtt gag ggc tgg 576 .

Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val Glu Gly Trp 180 185 190

gag ccg tca tcc aac aac gcg aac acg ggc att gga gga cac gga age 624

Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly His Gly Ser195 200 205

tgc tgc tet gag atg gat ate tgg gag gcc aac tcc ate tcc gag gct 672

Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu Ala210 215 220

ctt acc ccc cac cct tgc acg act gtc ggc cag gag ate tgc gag ggt 720

Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile Cys Glu Gly225 230 235 240

gat ggg tgc ggc gga act tac tcc gat aac aga tat ggc ggc act tgc 768

Asp Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr Cys245 250 255

gat ccc gat ggc tgc gac tgg aac cca tac cgc ctg ggc aac acc ageAsp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr Ser

816260

ttc tac ggc cct ggc tcaPhe Tyr Gly Pro Gly Ser275

acc gtt gtc acc cag ttcThr Val Val Thr Gln Phe295

265

age ttt acc ctc gat accSer Phe Thr Leu Asp Thr280

gag acg tcg ggt gcc ateGlu Thr Ser Gly Ala Ile295 300

270

acc aag aaa ttg 864

Thr Lys Lys Leu

285

aac cga tac tat 912

Asn Arg Tyr Tyr

gtc cag aat ggc gtc act ttc cag cag ccc aac gcc gag ctt ggt .agt 960

Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly Ser305 310 315 320

tac tet ggc aac gag ctc aac gat gat tàc tgc aca gct gag gag gea 1008

Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu Ala325 330 335

gaa ttc ggc gga tcc tet ttc tca gac aag ggc ggc ctg act cag ttc 1056Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln Phe340 345 350

aag aag gct acc tet ggc ggc atg gtt ctg gtc atg agt ctg tgg gat 1104

Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser Leu Trp Asp355 360 365

gat tac tac gcc aac atg ctg tgg ctg gac tcc acc tac. ccg aca aac 1152

Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr Asn370 375 380

gag acc tcc tcc aca ccc ggt gcc gtg cgc gga age tgc tcc acc age 1200

Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys Ser Thr Ser385 390 395 400

tcc ggt gtc cct, gct cag gtc gaa tet cag tet ccc aac gcc aag gtc 1248

Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn Ala Lys Val405 410 415

acc ttc tcc aac ate aag ttc gga ccc att ggc age acc ggc aac cct 1296

Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn Pro420 425 430

age ggc ggc aac cct ccc ggc gga.aac ccg cct ggc acc acc acc acc 134 4

Ser Gly Gly Asn Pro Pro' Gly Gly Asn Pro Pro Gly Thr Thr Thr Thr435 440 445

cgc cgc cca gcc act acc act gga age tet ccc gga cct acc cag tet 1392

Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro Thr Gln Ser450 455 460

cac tac ggc cag tgc ggc ggt att ggc tac age ggc ccc acg gtc tgc 1440

His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro ThrVal Cys465 470 475 480

gcc age ggc aca act tgc cag gtc ctg aac cct tac tac tet cag tgc' 1488Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr Ser Gln- Cys485 490 495

ctg taa 1494

Leu<210> 16

<211> 497

<212> PRT

<213> Trichoderma reesei

<400> 16

Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro Leu Thr Trp1 5 10 15

Gln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser Val20 25 30

Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn Ser Ser Thr35 40 45

Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp Asn50 55 60

Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala Ser65 70 75 80

Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe Val85 90 95

Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr Leu Met Ala100 105 110

Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe Ser115 120 125

Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala Leu130 135 140

Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro Thr145 150 155 160

Asn Thr Ala Gly Ala Lys Tyr GlyiThr Gly Tyr Cys Asp Ser Gln Cys165 170 175

Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val Glu Gly Trp180 185 190

Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly His Gly Ser195 200 205Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu Ala210 215 220

Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile Cys Glu Gly225 230 235 240

Asp Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr Cys245 250 255

Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr Ser260 265 270

Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys Leu275 280 285

Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr Tyr290 295 300

Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly Ser305 310 315 320

Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu Ala325 330 335

Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln Phe340 345 350

Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser Leu Trp Asp355 360 365

Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr Asn370 375 380

Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys Ser Thr Ser385 390 395 400

Ser Gly Val Pro Ala Gln Val Glu Ser' Gln Ser Pro Asn Ala Lys Val405 410 415

Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn Pro420 425 430

Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr Thr Thr Thr435 440 445

Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro Thr Gln Ser450 455 460

His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val Cys465 470 475 480

Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr Ser Gln Cys485 490 495

Leu

<210> 17

<211> 1494

<212> DNA

<213> Trichoderma reesei

<220>

<221> CDS<222> (1)..(1494)

<400> 17

cag tcg gcc tgc act ctc caa tcg gag act cac ccg cct ctg aca tgg 48

Gln Ser. Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro Leu Thr Trp1 5 10 15

cag aaa tgc tcg tct ggt ggc acg tgc ..act caa ca.g aca ggc tcc gtg 96

Gln Lys Cys Ser Ser Gly Gly Thr Cys:Thr Gln Gln Thr Gly Ser Val

20 25 30

gtc ate gac gcc aac tgg cgc tgg act cac gct acg aac age age acg 144

Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala-Thr Asn Ser Ser Thr35 40 45

aac tgc tac gat ggc aac act tgg age tcg- acc cta tgt cct gac aac 192

Asn Cys Tyr AspiGly Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp Asn50 1 55 60

gag acc tgc gcg aag aac tgc tgt ctg gac ggt gcc gcc tac gcg tcc 240

Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala Ser65 70 75 80

acg tac gga gtt acc acg age ggt aac age ctc tcc att ggc ttt gtc 288

Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe Val85 90 95

acc cag tct gcg cag aag aac gtt ggc gct cgc ctt tac ctt atg gcg 336

Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr Leu Met Ala100 105 110

age gac acg acc tac cag gaa ttc acc ctg ctt ggc aac gag ttc tct 384

Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe Ser115 120 125

ttc gat gtt gat gtt tcg cag ctg ccg tgc ggc ttg aac gga gct ctcPhe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala Leu130 135 140

432tac ttc gtg tcc atg gac gcg gat ggt ggc gtg age aag tat ccc acc 480

Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro Thr145 150 155 160

aac acc gct ggc gcc aag tac ggc acg ggg tac tgt gac age cag tgt 528

Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln Cys165 170 175

ccc cgc gat ctg aag ttc ate aat ggc cag gcc aac gtt gag ggc tgg 576

Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val Glu Gly Trp180 185 190

gag ccg tcá tcc aac aac gcg aac acg ggc att gga gga cac gga age 624

Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly His Gly Ser195 200 205

tgc tgc tet gag atg gat ate tgg gag gcc aac tcc ate tcc gag gct 672

Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu Ala210 215 220

ctt acc ccc cac cct tgc acg act gtc ggc cag gag ate tgc gag ggt 720

Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile Cys Glu Gly225 230 235 240

gat ggg tgc ggc gga act tac tcc gat aac aga tat ggc ggc act tgc 768

Asp- Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr Cys245 25.0 255

gat ccc gat ggc tgc gac tgg aac cca tac cgc ctg ggc aac acc age 816

Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr Ser260 265 270

ttc tac ggc cct ggc tca age ttt acc ctc gat acc acc aag aaa ttg 864

Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys Leu275 280 285

acc gtt gtc acc cag ttc gag acg tcg ggt gcc ate aac cga tac tat 912

Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr Tyr290 295 300

gtc cag aat ggc gtc act ttc cag cag ccc aac gcc gag ctt ggt agt 960

Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly Ser305 310 315 320

tac tet ggc aac gag ctc aac gat gat tac tgc aca gct gag gag gea 1008

Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu Ala325 330 335

gaa ttc ggc gga tcc tet ttc tca gac aag ggc ggc ctg act cag ttc 1056

Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln Phe340 345 350

aag aag gct acc tet ggc ggc atg gtt ctg gtc atg agt ctg tgg gat 1104

Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser Leu Trp Asp355 360 365

gat tac tac gcc aac atg ctg tgg ctg gac tcc acc tac ccg aca aacAsp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr Asn370 375 380

1152gag acc tcc tcc aca ccc ggt gcc gtg cgc gga age tgc tcc acc age - 1200Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys Ser Thr Ser385 390 395 400

tcc ggt gtc cct gct cag gtc gaa tet cag tet ccc aac gcc aag gtc 1248

Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn Ala Lys Val405 410 415

acc ttc tcc aac ate aag ttc gga ccc att ggc age acc ggc aac cct 1296

Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn Pro420 425 430

age ggc ggc aac cct ccc ggc gga aac ccg cct ggc acc acc acc acc 1344

Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr Thr Thr Thr435 440 445

cgc cgc cca gcc act acc act gga age tet ccc gga cct acc cag tet 1392

Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro Thr Gln Ser450 455 460

cac tac ggc cag tgc ggc ggt att ggc tac age ggc ccc acg gtc tgc 14 40

His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val Cys465 470 475 480

gcc age ggc aca act tgc cag gtc ctg aac cct tac tac tet cag tgc 1488

Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr Ser Gln Cys485 490 495

ctg taa 1494

Leu

<210> 18

<211> 497

<212> PRT -

<213> Trichoderma reesei

<4 00> 18

Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro Leu Thr Trp1 5 10 15

Gln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser Val20 25 30

Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn Ser Ser Thr35 40 45

Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp Asn50 55 60

Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala Ser65 70 75 80

Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe Val85 90 95

Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr Leu Met Ala100 105 110

Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe Ser115 120 125

Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala Leu130 135 140

Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro Thr145 150 155 160

Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln Cys165 170 175

Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val Glu Gly Trp180 185 190

Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly His Gly Ser195 200 205

Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu Ala210 215 220

Leu Thr Pro His Pro Cys Thr Thr Val Gly Gl-n Glu Ile Cys Glu Gly225 230 235 240

Asp Gly Cys GlyjGly Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr Cys245 250 255

Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr Ser260 265 270

Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys Leu275 280 285

Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr Tyr290 295 300

Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly Ser305 310 315 320

Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu Ala325 330 335Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln Phe340 345 350

Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser Leu Trp Asp355 360 365

Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr Asn370 375 380

Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys Ser Thr Ser385 390 395 400

Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn Ala Lys Val405 410 415.

Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn Pro420 425 430

Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr Thr Thr Thr4 35 440 445

Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser. Pro Gly Pro Thr Gln Ser450 455 . . 460

His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val Cys465' 470 475 480

Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr Ser Gln Cys'485 490 495

Leu

<210> 19

<211> 1344

<212> DNA

<213> Trichodérma reesei

<220>

<221> CDS

<222> (1)..(1344)

<4 00> 19

caa gct tgc tca age gtc tgg ggc caa tgt ggt ggc cag aat tgg tcg 48

Gln Ala Cys Ser Ser Val Trp Gly Gln Cys Gly Gly Gln Asn Trp Ser1 5 10 15ggt ccg act tgc tgt gct tcc gga age aca tgc gtc tac tcc aac gacGly Pro Thr Cys Cys Ala Ser Gly Ser Thr Cys Val Tyr Ser Asn Asp20 25 30

tat tac tcc cag tgt ctt ccc ggc gct gea age tca age tcg tcc acgTyr Tyr Ser Gln Cys Leu Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr35 40 45

cgc gcc gcg tcg acg act tet cga gta tcc ccc aca aca tcc cgg tcgArg Ala Ala Ser Thr Thr Ser Arg Val Ser Pro Thr Thr Ser Arg Ser50 55 60

age tcc gcg acg cct cca cct ggt tet act act acc aga gta cct ccaSer Ser Ala Thr Pro Pro Pro Gly Ser Thr Thr Thr Arg Val Pro Pro65 70 75 80

gtc gga tcg gga acc gct acg tat tca ggc aac cct ttt gtt ggg gtcVal Gly Ser Gly Thr Ala Thr Tyr Ser Gly Asn Pro Phe Val Gly Val85 90 95

act cct tgg gcc aat gea tat tac gcc tet gaa gtt age age ctc gctThr Pro Trp Ala Asn Ala Tyr Tyr Ala Ser Glu Val Ser Ser Leu Ala100 105 110

att cct age ttg act gga gcc atg gcc act gct gea gea gct gtc geaIle Pro Ser Leu Thr Gly Ala Met Ala Thr Ala Ala Ala Ala Val Ala115 120 125

aag gtt ccc tet ttt atg tgg cta gat act ctt gaç aag acc cct ctcLys Val Pro Ser Phe Met Trp Leu Asp Thr Leu Asp Lys Thr Pro Leu130 135 140

atg gag eaa acc ttg gcc gac ate cgc acc gcc aac aag aat ggc ggtMet Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala Asn Lys Asn Gly Gly145 150 155 ' 160

aac tat gcg gga cag ttt gtg gtg tat gac ttg ccg gat cgc gat tgcAsn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu Pro Asp Arg Asp Cys165 170 175

gct gcc ctt gcc tcg aat ggc gaa tac tet att gcc gat ggt ggc gtcAla Ala Leu1Ala Ser Asn Gly Glu Tyr Ser Ile Ala Asp Gly Gly Val180 185 190

'gcc aaa tat aag aac tat ate gac acc att cgt caa att gtc gtg gaaAla Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg Gln Ile' Val Val Glu195 200 205

tat tcc gat ate cgg acc ctc ctg gtt att gág cct gac tet ctt gccTyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu Pro Asp Ser Leu Ala210 215 220

aac ctg gtg acc aac ctc ggt act cca aag tgt gcc aat gct cag tcaAsn Leu Val Thr Asn Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser225 230 235 240

gcc tac ctt gag tgc ate aac tac gcc gtc aca cag ctg'aac ctt ccaAla Tyr Leu Glu Cys Ile Asn Tyr Ala Val Thr Gln Leu Asn Leu Pro245 250 255

aat gtt gcg atg tat ttg gac gct ggc cat gea gga tgg ctt ggc tggAsn Val Ala Met Tyr Leu Asp Ala Gly His Ala Gly Trp Leu Gly Trp260 265 270

ccg gca aac caa gac ccg gcc gct cag cta ttt gca aat gtt tac aag 864

Pro Ala Asn Gln Asp Pro Ala Ala Gln Leu Phe Ala Asn Val Tyr Lys275 280 285

aat gca tcg tct ccg aga gct ctt cgc gga ttg gca acc aat gtc gcc 912

Asn Ala Ser Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr Asn Vai,Ala290 295 300

aac tac aac ggg tgg aac att acc age ccc cca tcg tac acg caa ggc 960

Asn Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln Gly305 310 315 320

aac gct gtc tac aac gag aag ctg tac ate cac gct att gga cgt ctt 1008

Asn Ala Val Tyr Asn Glu Lys Leu Tyr Ile His Ala Ile Gly Arg Leu325 330 335

ctt gcc aat cac gg.c tgg tcc aac gcc ttc ttc ate act gat caa ggt 105 6

Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe Ile Thr Asp Gln Gly340 '345 350

cga tcg gga aag cag cct acc gga cag caa cag tgg gga gac tgg tgc 1104

Arg Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp Cys355 360 365

aat g.tg ate ggc acc gga ttt ggt att cgc cca tcc gca aac act ggg 1152Asn Val Ile Gly Thr Gly Phe Gly Ile Arg Pro Ser Ala Asn Thr Gly370 375 380

gac tcg ttg ctg gat tcg ttt gtc tgg gtc aag cca ggc ggc gag tgt 1200

Asp Ser Leu Leu Asp Ser Phe Val Trp Val Lys Pro Gly Gly Glu Cys385 390 395 400

gac ggc acc age gac age agt gcg cca cga ttt gac tcc cac tgt gcg 1248

Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser His Cys Ala405 410 415

etc cca gat gcc ttg caa ccg gcg gct caa gct ggt gct tgg ttc caa 1296

Leu Pro Asp Ala Leu Gln Pro Ala Ala Gln Ala Gly Ala Trp Phe Gln420 425 430

gcc tac ttt gtg cag ctt etc a ca aac gca aac cca tcg ttc ctg taa 1344

Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu435 440 445

<210> 20<211> 447<212> PRT

<213> Trichoderma reesei<400> 20

Gln Ala Cys Ser Ser Val Trp Gly Gln Cys Gly Gly Gln Asn Trp Ser1 5 10 15

Gly Pro Thr Cys Cys Ala Ser Gly Ser Thr Cys Val Tyr Ser Asn Asp20 25 30Tyr Tyr Ser Gln Cys Leu Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr35 40 45

Arg Ala Ala Ser Thr Thr Ser Arg Val Ser Pro Thr Thr Ser Arg Ser50 55 60

Ser Ser Ala Thr Pro Pro Pro Gly Ser Thr Thr Thr Arg Val Pro Pro65 70 75 80

Val Gly Ser Gly Thr Ala Thr Tyr Ser Gly Asn Pro Phe Val Gly Val85 90 95

Thr Pro Trp Ala Asn Ala Tyr Tyr Ala Ser Glu Val Ser Ser Leu Ala100 105 110

Ile Pro Ser Leu Thr Gly Ala Met Ala Thr Ala Ala Ala Ala Val Ala115 ■ 120 125

Lys Val Pro Ser Phe Met Trp Leu Asp Thr Leu Asp Lys Thr Pro Leu130 135 140

Met Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala Asn Lys Asn Gly Gly145 150 155 160

Asn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu Pro Asp Arg Asp Cys165 170 175

Ala Ala Leu Ala Ser Asn Gly Glu Tyr Ser Ile Ala Asp Gly Gly Val180 ' 185 190

Ala Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg Gln Ile Val Val Glu195 200 205

Tyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu Pro Asp Ser Leu Ala210 215 220

Asn Leu Val Thr Asn Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser225 230. 235 240

Ala Tyr Leu Glu Cys Ile Asn Tyr Ala .Val Thr Gln Leu Asn Leu Pro245 250 255

Asn Val Ala Met Tyr Leu Asp Ala Gly His Ala Gly Trp Leu Gly Trp260 265 270Pro Ala Asn Gln Asp Pro Ala Ala Gln Leu .Phe Ala Asn Val Tyr Lys275 280 285

Asn Ala Ser Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr Asn Val Ala290 295 300

Asn Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln Gly305 310 315 320

Asn Ala Val Tyr Asn Glu Lys Leu Tyr Ile His Ala Ile Gly Arg Leu325 330 335

Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe Ile Thr Asp Gln Gly340 345 350

Arg Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp Cys355 360 365

Asn Val He Gly Thr Gly Phe Gly Ile Arg Pro Ser Ala Asn Thr Gly370 375 380

Asp Ser Leu Leu Asp Ser Phe Val Trp Val Lys Pro Gly Gly Glu Cys385 390 39.5 400

Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser His Cys Ala405 410 415

Leu Pro Asp Ala Leu Gln Pro Ala Ala Gln Ala Gly Ala Trp Phe Gln420 425 430

Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu435 440 445

<210> 21

<211> 1230

<212> DNA

<213> Trichoderma reesei

<220>

<221> CDS<222> (1)..(1230)

<400> 21

ccc ggc gct gca age tca age tcg tcc acg cgc gcc gcg tcg acg act 4Í

Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr Thr1 5 10 15

tet cga gta tcc ccc aca aca tcc cgg tcg age tee gcg acg cct cca

96Ser Arg Val Ser Pro Thr Thr Ser Arg Ser Ser Ser Ala Thr Pro Pro20 25 30

cct ggt tct act act acc aga gta cct cca gtc gga tcg gga acc gct 144

Pro Gly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser Gly Thr Ala35 40 45

acg tat tca ggc aac cct ttt gtt ggg gtc act cct tgg gcc aat gca 192

Thr Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp Ala Asn Ala50 55 60

tat tac gcc tct gaa gtt age age ctc gct att cct age ttg act gga 240

Tyr Tyr Ala Ser Glu Val Ser Ser Leu Ala Ile Pro Ser Leu Thr Gly65 70 75 . 80

gcc atg gcc act gct gca gca gct gtc gca aag gtt ccc tct ttt atg 288

Ala Met Ala Thr Ala Ala Ala Ala Val Ala Lys Val Pro Ser Phe Met85 90 95

tgg cta gat act ctt gac aag acc cct ctc atg gag ca.a acc ttg gcc 336

Trp Leu Asp Thr Leu Asp Lys Thr Pro Leu Met Glu Gln Thr Leu Ala100 105 110

gac ate cgc acc gcc aac aag aat ggc ggt aac tat gcg gga çag ttt 384

Asp Ile Arg Thr Ala Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln Phe115 120 125

gtg gtg tat gac ttg ccg gat cgc gat tgc gct gcc ctt gcc tcg aat 432

Val Val Tyr Asp Leu Pro Asp Arg Asp Cys Ala Ala Leu Ala Ser Asn130 135 140

ggc gaa tac tct att gcc gat ggt ggc gtc gcc aaa tat aag aac tat 480

Gly Glu Tyr Ser Ile Ala Asp Gly Gly Val Ala Lys Tyr Lys Asn Tyr145 150 155 160

ate gac acc att cgt caa att gtc gtg gaa tat tcc gat ate cgg acc 528

Ile Asp Thr Ile Arg Gln Ile Val Val Glu Tyr Ser Asp Ile Arg Thr165 170 175

ctc ctg gtt att gag cct gac tct ctt gcc aac ctg gtg acc aac ctc 576

Leu Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val Thr Asn Leu180 185 190

ggt act cca aag tgt gcc aat gct cag tca gcc tac ctt gag tgc ate 624

Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala Tyr Leu Glu Cys Ile195 200 205

aac tac gcc gtc aca cag ctg aac ctt cca aat gtt gcg atg. tat ttg 672

Asn Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala Met Tyr Leu210 215 220

gac gct ggc cat gca gga tgg ctt ggc tgg ccg gca aac caa gac ccg 720

Asp Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp Pro225 230 235 240

gcc gct cag cta ttt gca aat gtt tac aag aat gca tcg tct ccg aga 768

Ala Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro Arg245 250 255

gct ctt cgc gga ttg gca acc aat gtc gcc aac tac aac ggg tgg aacAla Leu Arg Gly Leu Ala Thr Asn Val Ala Asn Tyr Asn Gly Trp Asn

816260 265 270

att acc age ccc cca tcg tac acg caa ggc aac gct gtc tac aac gagIle Thr Ser Pro Pro Ser Tyr Thr Gln Gly Asn Ala Val Tyr Asn Glu275 280 285

aag ctg tac ate cac gct att gga cgt ctt ctt gcc aat cac ggc tggLys Leu Tyr Ile His Ala Ile Gly Arg Leu Leu Ala Asn His Gly Trp290 295 300

tcc aac gcc ttc ttc ate act gat caa ggt cga tcg gga aag cag cctSer Asn Ala Phe Phe Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln Pro305 310 315 320

acc gga cag caa cag tgg gga gac tgg tgc aat gtg ate ggc acc ggaThr Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile Gly Thr Gly325 330 335

ttt ggt att cgc cca tcc gea aac act ggg gac tcg ttg ctg gat tcgPhe Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp Ser340 345 350

ttt gtc tgg gtc aag cca ggc ggc gag tgt gac ggc acc age gac agePhe Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp Ser355 360 3 65

agt gcg cca cga ttt gac tcc cac tgt gcg ctc cca gat gcc ttg caaSer Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp Ala Leu Gln370 375 380

ccg gcg gct caa gct ggt gct tgg ttc caa gcc tac ttt gtg cag cttPro Ala Ala Gln Ala Gly Ala Trp Phe Gln "Ala Tyr Phe VaI Gln Leu385 390 395 400

ctc aca aac gea aac cca tcg ttc ctg taaLeu Thr Asn Ala Asn Pró Ser Phe Leu405

<210> 22

<22I> 409

<212> PRT

<213> Trichoderma reesei

<400> 22

Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr Thr1 5 10 15

Ser Arg Val Ser Pro Thr Thr Ser Arg Ser Ser Ser Ala Thr Pro Pro20 25 30

Pro Gly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser Gly Thr Ala35 40 45

Thr Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp Ala Asn Ala50 55 60Tyr Tyr Ala Ser Glu Val Ser Ser Leu Ala Ile Pro Ser Leu Thr Gly65 70 75 80

Ala Met Ala Thr Ala Ala Ala Ala Val Ala Lys Val Pro Ser Phe Met85 90 95

Trp Leu Asp Thr Leu Asp Lys Thr Pro Leu Met Glu Gln Thr Leu Ala100 105 110

Asp Ile Arg Thr Ala Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln Phe115 120 125

Val Val Tyr Asp Leu Pro Asp Arg Asp Cys Ala Ala Leu Ala Ser Asn130 135 140

Gly Glu Tyr Ser Ile Ala Asp Gly Gly Val Ala Lys Tyr Lys Asn.,,Tyr145 150 155 160

Ile Asp Thr Ile Arg Gln Ile Val Val Glu Tyr Ser Asp Ile Arg Thr165 170 175

Leu Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val Thr Asn Leu180 185 190

Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala,Tyr Leu Glu Cys Ile195 200 205

Asn Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala Met Tyr:Leu210 215 220

Asp Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp..Pro225 230 235 240

Ala Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro Arg245 250 255

Ala Leu Arg Gly Leu Ala Thr Asn Val Ala Asn Tyr Asn Gly Trp Asn260 265 270

Ile Thr Ser Pro Pro Ser Tyr Thr Gln Gly Asn Ala Val Tyr Asn Glu275 280 285

Lys Leu Tyr Ile His Ala Ile Gly Arg Leu Leu Ala Asn His Gly Trp290 295 300Ser Asn Ala Phe Phe Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln Pro 305 310 315 320

Thr Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile Gly Thr Gly325 330 335

Phe Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp Ser340 345 350

Phe Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp Ser355 360 365

Ser Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp Ala Leu Gln370 375 380

Pro Ala Ala Gln Ala Gly Ala Trp Phe Gln Ala Tyr Phe Val Gln Leu385 330 395 400

Leu Thr Asn Ala Asn Pro Ser Phe Leu405

<210> 23<211> 1314<212> DNA<213> Trichoderma reesei

<220><221> CDS<222> (1)..(1314)

<400> 23

cag caa ccg ggt acc age acc ccc gag gtc cat ccc aag ttg aca acc 48Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys Leu Thr Thr1 5 10 15

tac aag tgt aca aag tcc ggg ggg tgc gtg gcc cag gac acc tcg gtg 96Tyr Lys Cys Thr Lys Ser Gly Gly Cys Val Ala Gln Asp Thr Ser Val20 25 30

gtc ctt gac tgg aac tacVal Leu Asp Trp Asn Tyr35

tgc acc gtc aac ggc ggcCys Thr Val Asn Gly Gly50

acc tgt ggc aag aac tgcThr Cys Gly Lys Asn Cys65 70

ggc gtc acg acc tcg ggcGly Val Thr Thr Ser Gly

cgc tgg atg cac gac geaArg Trp Met His Asp Ala40

gtc aac acc acg ctc tgcVal Asn Thr Thr Leu Cys55 60

ttc ate gag ggc gtc gacPhe Ile Glu Gly Val Asp75

age age ctc acc atg aacSer Ser Leu Thr Het Asn

aac tac aac tcg 144

Asn Tyr Asn Ser45

cct gac gag gcg 192

Pro Asp Glu Ala

tac gcc gcc tcg 240

Tyr Ala Ala Ser80

cag tac atg ccc 288

Gln Tyr Met Pro85 90 95

age age tet ggc ggc tac age age gtc tet cct cgg ctg tat etc ctg 336

Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu Leu100 105 110

gac tet gac ggt gag tac gtg atg ctg aag etc aac ggc cag gaçr ctg 384

Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly Gln Glu Leu115 120 125

age ttc gac gtc gac ctc tet gct ctg ccg tgt gga gag aac. ggc tcg 432

Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly Ser130 135 140

ctc tac ctg tet cag atg gac gag aac ggg ggc gcc aac.cag tat aac 480

Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr Asn145 150 155 160

acg gcc ggt gcc aac tac ggg age ggc tac tgc gat gct cag tgc ccc 528

Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala Gln Cys Pro165 170 175

gtc cag aca tgg agg aac ggc acc ctc aac act age cac cag ggc ttc 576

Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His Gln Gly Phe180 185 190

tgc tgc aac gag atg gat ate ctg gag ggc aac tcg agg gcg aat gccCys Cys-Asn Glu Met Asp Ile Leu Glu GlyAsn Ser Arg Ala Asn Ala195 200 205

624

ttg acc cct cac tet tgc acg gcc acg gcc. tgc gac tet gcc ggt tgc 672

Leu Thr Pro His Ser Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly Cys210 215 220

ggc ttc aac ccc tat ggc age ggc tac aaa age tac tac ggc. ccc gga 720

Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly225 230 235 240

gat acc gtt gac acc tcc aag ate ttc acc ate ate acc cag ttc aac 768

Asp Thr Val Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr Gln Phe Asn

245 250 255

acg. gac aac ggc tcg ccc tcg ggc aac ctt gtg age ate acc cgc aag 816

Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile Thr Arg Lys260 265 270

tac cag caa aac ggc gtc gac ate ccc age gcc cag ccc ggc ggc gac 864

Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro Gly Gly Asp275 280 285

acc ate tcg tcc tgc.ccg tcc gcc tca gcc tac ggc ggc etc gcc acc 912

Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala Thr290 295 300

atg ggc aag gcc ctg age áge ggc atg gtg ctc gtg ttc age att tgg 960

Met Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe Ser Ile Trp305 310 315 320

aac gac aac age cag tac atg aac tgg ctc gac age ggc aac gcc ggc 1008

Asn Asp Asn Ser Gln Tyr Meit Asn Trp Leu Asp Ser Gly Asn Ala Gly

325 330 335ccc tgc age age acc gag ggc aac cca tcc aac ate ctg gcc aac aac 1056

Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Ásn Ile Leu Ala Asn Asn340 345 350

ccc aac acg cac gtc gtc ttc tcc aac ate cgc tgg gga gac att ggg 1104

Pro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly Asp Ile Gly355 360 365

tet act acg aac tcg act gcg ccc ecg ccc ccg cct gcg tcc age acg 1152

Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser Thr370 375 380

acg ttt tcg act aca cgg agg age tcg acg act tcg age age ccg age 1200Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser Ser Pro Ser385 390 395 400

tgc acg cag act cac tgg ggg cag tgc ggt ggc att ggg tac age ggg 1248

Cys Thr Gln Thr His Trp Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly405 410 415

tgc aag acg tgc acg tcg ggc act acg tgc cag tat age aac gac tac 1296Cys Lys Thr Cys Thr Ser Gly Thr Thr Cys Gln Tyr Ser Asn Asp Tyr420 425 430

tac tcg caa tgc ctt tag 1314

Tyr Ser Gln Cys Leu435

<210> 24<211> 437<212> PRT

<213> Trichoderma reesei

<400> 24

Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys Leu Thr Thr1 5 10 15

Tyr Lys Cys1Thr Lys Ser Gly Gly Cys Val Ala Gln Asp Thr Ser Val20 25 30

Val Leu Asp Trp Asn Tyr Arg Trp Met His Asp Ala Asn Tyr Asn Ser35 40 45

Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro Asp Glu Ala50 55 60

Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala Ser65 70 75 80

Gly Val Thr Thr Ser Gly Ser Ser Leu Thr Met Asn Gln Tyr Met Pro85 90 95Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu Leu100 105 110

Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly Gln Glu Leu115 120 125

Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly Ser130 135 140

Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr Asn145 150 155 160

Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala Gln Cys Pro165 170 175

Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His Gln Gly Phe180 185 190

Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn Ala195 200 205

Leu Thr Pro His Ser _Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly Cys210 215 220

Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly225 230 235 240

Asp Thr Val Asp ThrSer Lys Thr Phe Thr Ile Ile Thr Gln Phe Asn245 250 255

Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile Thr Arg Lys' 260 265 270

Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro Gly Gly Asp275 280 285

Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala Thr290 295 300

Met Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe Ser Ile Trp305 310 315 320

Asn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala Gly325 330 335

Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn AsnPro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly Asp Ile Gly355 360 365

Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser Thr370 375 380

Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser Ser Pro Ser385 390 395 400

Cys Thr Gln Thr His Trp Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly405 410 415

Cys Lys Thr Cys Thr Ser Gly Thr Thr Cys Gln Tyr Ser Asn Asp Tyr420 425 430

Tyr Ser Gln Cys Leu435

<210> 25

<211> 1200

<212> DNA

<213> Trichoderma reesei

<220>

<221> CDS

<222> (1)..(1200)

<400> 25

cag caa ccg ggt acc age acc ccc gagGln Gln Pro Gly lThr Ser Thr Pro Glu1 5

tac aag tgt aca aag tcc ggg ggg tgcTyr Lys Cys Thr Lys Ser Gly Gly Cys20 25

gtc ctt gac tgg aac tac cgc tgg atgVal Leu Asp Trp Asn Tyr Arg Trp Met35 40

gtc cat ccc aag ttg aca acc 4 8

Val His Pro Lys Leu Thr Thr10 15

gtg gcc cag gac acc tcg gtg 96

Val Ala Gln Asp Thr Ser Val30

cac gac gea aac tac aac tcg 144

His Asp Ala Asn Tyr Asn Ser45

tgc acc gtc aac ggc ggc gtc aac acc acg ctc tgc cct gac gag gcg 192

Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro Asp Glu Ala50 55 60

acc tgt ggc aag aac tgc ttc ate gag ggc gtc gac tac gcc gcc tcg 240

Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala Ser65 70 75 80

ggc gtc acg acc tcg ggc age-age ctc acc atg aac cag tac atg ccc 288

Gly Val Thr Thr Ser Gly Ser Ser Leu Thr Met Asn Gln Tyr Met Pro85 90 95age age tet ggc ggc tac age age gtc tet cct cgg ctg tat ctc ctg 336

Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu Leu100 105 110

gac tet gac ggt gag tac gtg atg ctg aag ctc aac ggc cag gag ctg 384

Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly Gln Glu Leu115 120 125

age ttc gac gtc gac ctc tet gct ctg ccg tgt gga gag aac ggc tcg 432

Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly Ser130 135 140

ctc tac ctg tet cag atg gac gag aac ggg ggc gcc aac cag tat aac 480

Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr Asn145 150 155 160

acg gcc ggt gcc aac tac ggg age ggc tac tgc gat gct cag tgc ccc 528

Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala Gln Cys Pro165 170 175

gtc cag aca tgg agg aac ggc acc ctc aac act age cac cag ggc ttc 576

Val Gln Thr Trp Arg Asn Gly Thr Leu AsnThr Ser His Gln Gly Phe180 185 190

tgc tgc aac gag atg gat ate ctg gag.ggc aac tcg agg gcg aat gcc 624

Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn Ala195 200 205

ttg acc cct cac tet tgc acg gcc acg gce·tgc gac tet gcc ggt tgc 672

Leu Thr Pro His Ser Cys Thr Ala Thr Alá Cys Asp Ser Ala Gly Cys210 215 220

ggc ttc aac ccc tat ggc age ggc tac aaa age tac tac ggc ccc gga 720

Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly225 230 235 240

gat acc gtt gac acc tcc aag acc ttc acc ate ate acc cag ttc aac 768

Asp Thr Val Asp Thr Ser Lys Thr Phe .Thr Ile Ile Thr Gln Phe Asn245 250 255

acg gac aac' ggc tcg ccc tcg ggc aac ctt gtg age ate acc cgc aag 816

Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile Thr Arg Lys260 265 270

tac cag caa aac ggc gtc gac ate ccc age gcc cag ccc ggc ggc gac 864

Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro Gly Gly Asp275 280 285

acc ate tcg tcc tgc.ccg tcc gcc tca gcc tac ggc ggc ctc gcc acc 912

Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala Thr290 295 300

atg ggc aag gcc ctg age age ggc atg gtg ctc gtg ttc age att tgg 960

Met Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe Ser Ile Trp305 310 315 320

aac gac aac age cag tac atg aac tgg ctc gac age ggc aac gcc ggcAsn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala Gly325 330 335

1008ccc tgc age age acc gag ggc aac cca tcc aac ate ctg gcc aac aac 1056Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn Asn340 345 350

ccc aac acg cac gtc gtc ttc tcc aac ate cgc tgg gga gac att ggg 1104

Pro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly Asp Ile Gly355 360 365

tet act acg aac tcg act gcg ccc ccg ccc ccg cct gcg tcc age acg 1152

Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser Thr370 375 380

1200

acg ttt tcg Thr Phe Ser 385 act Thr acá Thr cgg Arg 390 agg Arg age Ser tcg Ser acg Thr act Thr 395 tcg Ser age Ser age Ser ccg Pro age Ser 400<210> 26 <211> 400 <212> PRT <213> Trichoderma reesei <400> 26 Gln Gln Pro Ί Gly Thr 5 Ser Thr Pro Glu Val 10 His Pro Lys Leu Thr 15 ThrTyr Lys Cys Thr 20 Lys Ser Gly Gly Cys 25 Val Ala Gln Asp Thr 30 Ser ValVal Leu Asp 35 Trp Asn Tyr Arg Trp 40 Met His Asp Ala Asn 4 5. Tyr Asn SerCys Thr Val 50 Asn Gly Gly Val Asn Thr Thr Leu Cys 60 Pro Asp Glu Ala

Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala Ser65 70 .75 80

Gly Val Thr Thr Ser Gly Ser Ser Leu Thr Met Asn Gln Tyr Met Pro85 90 95

Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu Leu100 105 110

Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly Gln Glu Leu115 120 125

Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly Ser130 135 140

Leu Tyr Leu. Ser Gln Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr Ásn145 150 155 160

Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala Gln Cys Pro165 170 175

Val Gln. Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His Gln Gly Phe180 185 190

Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn Ala195 200 205

Leu Thr Pro His Ser Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly Cys210 215 220

Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly225 230 235 240

Asp Thr Val Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr Gln Phe Asn245 250 255

Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile Thr Arg Lys260 265 270

Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro Gly Gly Asp275 280 285

Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala Thr290 295 300

Met Gly Lys Alá Leu Ser Ser Gly Met Val Leu Val Phe Ser Ile Trp305 310 315 320

Asn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala Gly325 330 335

Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn Asn340 345 350

Pro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly Asp Ile Gly355 360 365

Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser Thr370 375 380

Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser Ser Pro Ser385 390 395 400<210> 27

<211> 138

<212> DNA

<213> Trichoderma reesei

<220>

<221> CDS<222> (1)..(138)

<400> 27

ggc tcg act tac tcc agt gga tct tct tcg ggg tcg ggg tct age tccGly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser1 5 10 15

age tcg agt tcg act acc act aag gcc act tcg acg acc ttg aag actSer Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr20 25 30

acc tcg acc acc age agt gga age agt tcg aca tcg-gcg gcgThr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala Ala35 40 45

<210> 28

<2l1> 46

<212> PRT

<213> Trichoderma reesei

<4 00> 28

Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser1 5 10 15

Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr20 25 30

Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala Ala35 40 45

<210> 29

<211> 2205

<212> DNA

<213> Seqüência artificial

<220>

<223> Proteína de fusão

<220>

<221> CDS

<222> (1)..(2205)

<400> 29

cag cag aat. tgc gea gea tta ttt ggc caa tgt gga ggc ata ggg tggGln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp.tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

96

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aacAsp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

144

pfeàSse

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gea tcc tca 192

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cagSer Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

288,

tet cct tac ccc age att gcc gea tcc agt tgc gga tcg tgg acc etcSer Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

336

gtg gat .aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tccVal Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

384

gag tca tgc tca ggc tgc ggt acc tgc ,act acg çcg ccc tcg gcg gacGlu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

432

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aacCys Lys Ser Gly Thr Met Tyr Pro Glu Val His- His Val Ser Ser Asn145 150 155 160

480

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggcGlu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

528

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gttGly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

576

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct tttThr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

624

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc cttCys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

672

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tggArg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

720

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgcSer Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

768att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln ThrLys Pro Asp Gly'Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

He, His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcç tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat. 1248Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att'gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat gcc tcc acg caa ggc 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Ala Ser Thr Gln Gly465 470 475 480

ate tcc gaa gac ctc tac aat cgc ttg gta gag atg gcc act ate tccIle Ser Glu Asp Leu Tyr Asn Arg Leu Val Glu Met Ala Thr Ile Ser485 490 495caa gcc gcc tac gcc gac cta tgc aat att cca tcg act att ate aaa ,· 1536Gln Ala Ala Tyr Ala Asp Leu Cys Asn Ile Pro Ser Thr Ile Ile Lys500 .505 510

gga gag aaa att tac aac gct caa act gat ate aac gga tgg ate ctc 1584

Gly Glu Lys Ile Tyr Asn Ala Gln Thr Asp Ile Asn Gly Trp Ile Leu515 520 525

cgc gac gac acc age aaa gaa att ate acc gtc ttc cgt ggc act ggc 1632

Arg Asp Asp Thr Ser Lys Glu Ile Ile Thr Val Phe Arg Gly Thr Gly530 535 540

agt gac aca aac cta cag ctc gat act aac tac acg ctc acg cca ttc 1680

Ser Asp Thr Asn Leu Gln Leu Asp Thr Asn Tyr Thr Leu Thr Pro Phe545 550 555 560

gac act cta cct caa tgc aac gat tgc gag gta cac ggt gga tac tat 1728

Asp Thr Leu Pro Gln Cys Asn Asp Cys Glu Val His Gly Gly Tyr Tyr565 - 570 575

att gga tgg ate tea gtc caa gac caa gtc gag tcg ctt gtc aaa caa 177 6

Ile Gly Trp Ile Ser Val Gln Asp Gln Val Glu Ser Leu Val Lys Gln580 " 585 . 590

cag gct age cag tat ccg gac tat gcg ctt acc gtg aca ggc cat agt 1824

Gln Ala Ser Gln Tyr Pro Asp Tyr Ala Leu Thr Val Thr Gly His Ser595 600 605

ctg gga gcg tcg atg gea gea ctc act gcc gcc ca.g ctg tcc gcg aca 1872

Leu Gly Ala Ser Met Ala Ala Leu Thr Ala Ala Gln Leu Ser Ala Thr610 615 620

tac gac aac gtc cgt ctg tac aca ttc ggc gaa ccg cgc age ggc aac 1920

Tyr Asp Asn Val Arg Leu Tyr Thr Phe Gly Glu Pro Arg Ser Gly Asn625 630 635 640

cag gcc ttc gcg tcg tac atg aac gat gcg ttc cag gtc tcg age ccg 1968

Gln Ala Phe Ala Ser Tyr Met Asn Asp Ala Phe Gln Val Ser Ser Pro645 650 655

gag acg acc cag tac ttc cgg gtc act cat tcc aac gac ggc ate cca 2016

Glu Thr Thr- Gln Tyr Phe Arg Val Thr His Ser Asn Asp Gly Ile Pro660 665 670

aac ttg ccc ccg gcg gac gag ggt tac gcc cat ggt ggt gta gag tac 2064

Asn Leu Pro Pro Ala Asp Glu Gly Tyr Ala His Gly Gly Val Glu Tyr675 680 685

tgg age gtt gat cct tac age gcc cag aac acg ttt gtc tgt act ggg 2112

Trp Ser Val Asp Pro Tyr Ser Ala Gln Asn Thr Phe Val Cys Thr Gly690 695 700

gat gaa gta cag tgc tgt gag gea cag ggc gga cag ggg gtg aat gat 2160

Asp Glu Val Gln Cys Cys Glu Ala Gln Gly Gly Gln Gly Val Asn Asp705 710 715 720

gcg cat act act tat ttt ggg atg acg age gga gct tgt act tggAla His Thr Thr Tyr Phe Gly Met Thr Ser Gly Ala Cys Thr Trp725 730 735

2205<210> 30

<211> 735

< 212 > PR-T

<213> Seqüência artificial<220>

<223> Construção Sintética

<400> 30

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln-85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 1 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met- Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp.Ala Phe195 200 205Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 ~ 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys -Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met;,Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 .350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr iPhe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Ala Ser Thr Gln Gly465 470 475 480

Ile Ser Gla Asp Leu Tyr Asn Arg Leu Val Glu Met Ala Thr Ile Ser485 490 495

Gln Ala Ala Tyr Ala Asp Leu Cys Asn Ile Pro Ser Thr Ile Ile Lys500 505 510

Gly Glu Lys Ile Tyr Asn Ala Gln Thr Asp Ile Asn Gly Trp Ile Leu515 520 525

Arg Asp Asp Thr Ser Lys Glu Ile Ile Thr Val Phe Arg Gly Thr Gly530 535 540

Ser Asp Thr Asn Leu Gln Leu Asp Thr Asn Tyr Thr Leu Thr Pro Phe545 550 555 560

Asp Thr Leu Pro Gln Cys Asn Asp Cys Glu Val His G'ly Gly Tyr Tyr565 570 575

Ile Gly Trp Ile Ser Val Gln Asp Gln Val Glu.Ser Leu Val Lys Gln580 585 590

Gln Ala Ser Gln Tyr Pro Asp Tyr Ala Leu Thr Val Thr Gly His Ser595 600 605

Leu Gly Ala Ser Met Ala Ala Leu Thr Ala Ala GlnLeu Ser Ala Thr610 615 620

Tyr Asp Asn Val Arg Leu Tyr Thr Phe Gly Glu Pro Arg Ser Gly Asn625 630 635 640

Gln Ala Phe Ala Ser Tyr Met Asn Asp Ala Phe Gln Val Ser Ser Pro645 650 655

Glu Thr Thr Gln Tyr Phe Arg Val Thr His Ser Asn Asp Gly Ile Pro660 665 670

Asn Leu Pro Pro Ala Asp Glu Gly Tyr Ala His Gly Gly Val Glu Tyr675 680 685

Trp Ser Val Asp Pro Tyr Ser Ala Gln Asn Thr Phe Val Cys Thr Gly690 695 700Asp Glu Val Gln Cys Cys Glu Ala Gln Gly Gly Gln Gly Val Asn Asp705 710 715 720

Ala His Thr Thr Tyr Phe Gly Met Thr Ser Gly Ala Cys Thr Trp725 730 735

<210> 31

<211> 2343

<213 > Seqüência artiticial

<223> Proteína de fusão

<220>

<221> CDS

<222> (1)..(2343)

<400> 31

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg 48Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

tcc ggc acc aca tgt tgc gtt .gct ggc gcc cag tgc agt ttt gtc aat 96Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 144Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tca 192Gly Thr Thr Ser ,Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 '55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg. cag 288Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc age att gcc gca tcc agt tgc gga tcg tgg acc ctc 336Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 432Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140tgc aaa tcc ggá acc atg tat cca gag gtc.cat cac gta tcc age aac 480

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt.ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 57 6

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

. aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 · 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 .230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Lau Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 . 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 8 64

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser.Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 i 295 300

tgc gga gag. ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser

305 310 315 320 '

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly ■ '·355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gcc 1200Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct çcg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat ggc tcg act tac tcc 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

agt gga tet tet tcg ggg tcg ggg tet age tcc age tcg agt tcg act 14 88

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

acc act aag gcc act tcg acg acc ttg aag act acc tcg acc acc age 1536

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

agt gga age agt tcg aca t.cg gcg gcg gcc tcc acg caa ggc ate tcc 1584

Ser Gly Ser Ser Ser Thr Ser Ala Ala Ala Ser Thr Gln Gly Ile Ser515 520 525

gaa gac ctc tac aat cgc ttg gta gag atg gcc act ate tcc caa gcc 1632

Glu Asp Leu Tyr Asn Arg Leu Val Glu Met Ala Thr Ile Ser Gln Ala530 535 540

gcc tac gcc gac cta tgc aat att cca tcg act att ate aaa gga gag 1680

Ala Tyr Ala Asp Leu Cys Asn Ile Pro Ser Thr Ile Ile Lys Gly Glu545 550 555 560

aaa att tac aac gct caa act gat ate aac gga tgg ate ctc cgc gac 1728

Lys Ile Tyr Asn Ala Gln Thr Asp Ile AsnGly Trp Ile Leu Arg Asp565 570 575

gac acc age aaa gaa att ate acc gtc ttc cgt ggc act ggc agt gac 1776

Asp Thr Ser Lys Glu Ile Ile Thr Val Phe Arg Gly Thr Gly Ser Asp580 585 590

aca aac cta cag ctc gat act aac tac acg ctc acg cca ttc gac act 1824

Thr Asn Leu Gln Leu Asp Thr Asn Tyr Thr Leu Thr Pro Phe Asp Thr595 600 605

cta cct caa tgc aac gat tgc gag gta cac ggt gga tac tat att gga 1872

Leu Pro Gln Cys Asn Asp Cys Glu Val His Gly Gly Tyr Tyr Ile Gly610 615 620

tgg ate tca gtc caa gac caa gtc gag tcg ctt gtc aaa caa cag gct 1920

Trp Ile Ser Val Gln Asp Gln Val Glu Ser Leu Val Lys Gln Gln Ala625

630

635

640

age cag tat ccg gac tat gcg ctt acc gt'g aca ggc cat agt ctg ggaSer Gln Tyr Pro Asp Tyr Ala Leu Thr Val Thr Gly His Ser Leu Gly645 650 655

1968

gcg tcg atg gea gea ctc act gcc gcc cag ctg tcc gcg aca tac gacAla Ser Met Ala Ala Leu Thr Ala Ala Gln Leu Ser Ala Thr Tyr Asp660 665 670

2016

aac gtc cgt ctg tac aca ttc ggc gaa ccg cgc age ggc aac cag gccAsn Val Arg Leu Tyr Thr Phe Gly Glu Pro Arg Ser Gly Asn Gln Ala675 680 685

2064

ttc gcg tcg tac atg aac gat gcg ttc cag gtc tcg age ccg gag acgPhe Ala Ser Tyr Met Asn Asp Ala Phe Gln Val Ser Ser Pro Glu Thr690 695 700

2112

acc cag tac ttc cgg gtc act cat tcc aac gac ggc ate cca aac ttgThr Gln Tyr Phe Arg Val Thr His Ser Asn Asp Gly Ile Pro Asn Leu705 710 -715 720

2160

CCC ccg gcg gac gag ggt tac gcc cat ggt ggt gta gag tac tgg agePro Pro Ala Asp Glu Gly Tyr Ala His Gly Gly Val Glu Tyr Trp Ser725 730 735

2208

gtt gat cct tac age gcc cag aac acg ttt gtc tgt act ggg gat gaaVal Asp Pro Tyr Ser Ala Gln Asn Thr-Phe Val Cys -Thr Gly Asp Glu740 745 750

2256

gta cag tgc tgt gag gea cag ggc gga cag ggg gtg aat gat gcg catVal Gln Cys Cys Glu Ala Gln Gly Gly Gln Gly Val Asn Asp Ala His755 760 765

2304

act act tat ttt ggg atg acg age gga gct tgt act tggThr Thr Tyr Phe Gly Met Thr Ser Gly Ala Cys Thr Trp770 775 780

2343

<210> 32 <211> 781 <212> <213> Seqüência artificial<220> <223> Construção Sintética< 400 > 32

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 -60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Glrv85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr.Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 ,155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His,Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys.Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 ; 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe.Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val4 20 425 ; 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr! Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 4 90 4 95

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 ■ 505 510

Ser Gly Ser Ser Ser Thr Ser Ala Ala Ala Ser Thr Gln Gly Ile Ser515 520 525

Glu Asp Leu Tyr Asn Arg Leu Val Glu Met Ala Thr Ile Ser Gln Ala530 535 540Ala Tyr Ala Asp Leu Cys Asn Ile Pro Ser Thr Ile Ile Lys Gly Glu545 550 555 560

Lys Ile Tyr Asn Ala Gln Thr Asp Ile Asn Gly Trp Ile Leu Arg Asp565 570 575

Asp Thr Ser Lys Glu Ile Ile Thr Val Phe Arg Gly Thr Gly Ser Asp580 585 590

Thr Asn Leu Gln Leu Asp Thr Asn Tyr Thr Leu Thr Pro Phe Asp Thr595 600 605

Leu Pro Gln Cys Asn Asp Cys Glu Val His Gly Gly Tyr Tyr Ile Gly610 615 620

Trp Ile Ser Val Gln Asp Gln Val Glu Ser Leu Val Lys Gln Gln Ala625 630 635 640

Ser Gln Tyr Pro Asp Tyr Ala Leu Thr Val Thr Gly His Ser Leu Gly64 5 650 655

Ala Ser Met Ala Ala Leu Thr Ala Ala Gln Leu Ser Ala Thr Tyr Asp660 665 670

Asn Val Arg Leu Tyr Thr Phe Gly Glu Pro Arg Ser Gly Asn Gln Ala

675 680 685

Phe Ala Ser Tyr Met Asn Asp Ala Phe Gln Val Ser Ser Pro Glu Thr690 695 700

Thr Gln Tyr Phe Arg Val Thr His Ser Asn Asp Gly Ile Pro Asn Leu705 710 715 720

Pro Pro Ala Asp Glu Gly Tyr Ala His Gly Gly Val Glu Tyr Trp Ser725 730 735

Val Asp Pro Tyr Ser Ala Gln Asn Thr Phe Val Cys Thr Gly Asp Glu740 745 750

Val Gln Cys Cys Glu Ala Gln Gly Gly Gln Gly Val Asn Asp Ala His755 760 765

Thr Thr Tyr Phe Gly Met Thr Ser Gly Ala Cys Thr Trp770 775 780<210> 33

<211> 2937

<212> DNA

<213 > Seqüência artificial

<220>

<223> Prpteinaide fusão

<220>

<221> CDS

<222> (1)..(2937)

<400> 33

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg 48Gln Gln Asn Cys Ala Ála Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp

1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aat 96Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 144Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tca 192Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag 288Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc age att gcc gca tcc agt tgc gga tcg tgg acc ctc 336Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 432Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 480Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 576Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln.' Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag -tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pr.o Gly Ala Asp His2 90 2 95 300

tgc gga gag ate gae ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 . 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt; ttg cag ggc aat 1008 .

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc- cca caa gaa cgc tat 124 8

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gttGly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

1296gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1.392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat gcg acc' gac ccc ttc 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Ala Thr Asp Pro Phe465 470 475 480

cag tcg cgg tgc aat gaa ttc cag aac aag ate gac ate gcc aat gtc 1488

Gln Ser Arg Cys Asn Glu Phe Gln Asn Lys Ile Asp Ile Ala Asn Val485 490 495

acc gtc aga tcg gtc gea tac gtt gct gct ggá cag aac ate tcc caa 1536

jgf Thr Val Arg Ser Val Ala Tyr Val Ala Ala Gly Gln Asn Ile Ser Gln

m .500 .505 510

gcg gag gtc gcc tcc gtg tgt aa-a gea tcg gtt caa gcc agt gtc gac 1584

Ala Glu Val Ala Ser Val Cys Lys Ala Ser Val Gln Ala Ser Val Asp515 520 525

ctg tgc cgg gta acc atg aac ate tcg acg tcg gat cgc age cat ctg 1632

Leu Cys Arg Val Thr.Met Asn Ile Ser Thr Ser Asp Arg Ser His Leu530 535 54 0

tgg gct gag gcc tgg ctc cca aga aat tat acc ggt cgc ttc gtg age 1680

Trp Ala Glu Ala Trp Leu Pro Arg Asri Tyr Thr Gly Arg Phe Val Ser545 550 555 560

acg ggg aat gga ggt cta gcc ggc tgt gtc caa gaa acg gac ctc aac 1728

Thr Gly Asn Gly Gly Leu Ala Gly Cys Vai Gln Glu Thr Asp Leu Asn5 65 570 575

ttt gea gcc aac ttt ggt ttc gct acc gtg ggc acc aac ggt gga cat 1776

Phe Ala Ala Asn Phe Gly Phe Ala Thr Val Gly Thr Asn Gly Gly His580 : 585 590

gac ggg gac acg gcc aaa tac ttc ctc aac aac tcg gag gtt ctg gcc 1824

Asp Gly Asp Thr Ala Lys Tyr Phe Leu Asn Asn Ser Glu Val Leu Ala595 600 605

gat ttt gcc tat cgc tca gtg cac gaa ggg acc gtg gtg ggt aag caa 1872

Asp Phe Ala Tyr Arg Ser Val His Glu Gly Thr Val Val Gly Lys Gln610 615 620.

cta act caa ttg ttt tat gac gag gga tac aac tac t.cc tac tat ttg 1920

Leu Thr Gln Leu Phe Tyr Asp Glu Gly Tyr Asn Tyr Ser Tyr Tyr Leu625 630 635 640

ggt tgc tcc acc gga ggc cgc caa ggc tac cag caa gtc caa cgg ttt 1968

Gly Cys Ser Thr Gly Gly Arg Gln Gly Tyr Gln Gln Val Gln Arg Phe645 650 655

ccc gac gac tat gac gga gtg att gcg ggc tcc gea gcg atg aac ttt 2016

Pro Asp Asp Tyr Asp Gly Val Ile Ala Gly Ser Ala Ala Met Asn Phe660 665 670ate aac ctg ate tcc tgg ggg gcc ttc ttg tgg aag gcg acg ggg tta 2064Ile Asn Leu Ile Ser Trp Gly Ala Phe Leu Trp Lys Ala Thr Gly Leu675 680 685

gcg gat gat cca gac ttt ate tet gea aac ctg tgg tcc gta ate cac 2112

Ala Asp Asp Pro Asp Phe Ile Ser Ala Asn Leu Trp Ser Val Ile His690 695 700

cag gag att gtt cgt cag tgc gac ctg gtc gat ggg gct ctg gat gga 2160Gln Glu Ile Val Arg Gln Cys Asp Leu Val Asp Gly Ala Leu Asp Gly705 710 715 720

ate ate gaa gac cct gat ttc tgt gct cca gtc ate gag cgc ttg ate 2208

Ile Ile Glu Asp Pro Asp Phe Cys Ala Pro Val Ile Glu Arg Leu Ile725 730 735

tgc gac ggg act acc aac ggc acc tet tgt ate acg gga gcc cag gea 2256

Cys Asp Gly Thr Thr Asn Gly Thr Ser Cys Ile Thr Gly Ala Gln Ala740 745 750

gea aag gtc aac cgg gcc ttg agt gac ttc tat ggc ccc gac ggg aca 2304

Ala Lys Val Asn Arg Ala Leu Ser Asp Phe Tyr Gly Pro Asp Gly Thr755 760 765

gtg tac tac ccg cgc ctg aac tat ggg ggt gag gcc gac.tcg gct tcc 2352Val Tyr Tyr Pro Arg Leu Asn Tyr -Gly Gly Glu Ala Asp Ser Ala Ser770 775 780

ctg. tac ttc acg ggg tcg atg tac age cgt acg gag gaa tgg tac aaa 2400

Leu Tyr Phe Thr Gly Ser Met Tyr Ser Arg Thr Glu Glu Trp Tyr Lys785 790 795 800

tat gtg gtc tat aac gac acc aac tgg aac tcc age cag tgg acg ctg 2448

Tyr Val Val Tyr Asn Asp Thr Asn Trp Asn Ser Ser Gln Trp Thr Leu805 810 815

gag agt gcc aag ctg gcc ctg gag cag aat ccg ttc aat ate cag gcg 2496

Glu Ser Ala Lys Leu Ala Leu Glu Gln Asn Pro Phe. Asn Ile Gln Ala820 825 830

ttt gat ccc aac ate acg gcc ttc cgg gac cgg ggt ggc aag ctg ctg 2544Phe Asp Pro Asn Ile Thr Ala Phe Arg Asp Arg Gly Gly Lys Leu Leu835 840 845

tcc tac cac ggc acg cag gat ccc att ate age tcc acg gat age aag 2592

Ser Tyr His Gly Thr Gln Asp Pro Ile Ile Ser Ser Thr Asp Ser Lys850 855 860

etc tac tac cga cgg gta gcg aat gcc ctg aat gcc gcg ccg tcc gag 2640

Leu Tyr Tyr Arg Arg Val Ala Asn Ala Leu Asn Ala Ala Pro Ser Glu865 870 875 880

cta gat gag ttc tat cgg ttc ttc cag ate tcc ggc atg ggc cac tgt 2688

Leu Asp Glu Phe Tyr Arg Phe Phe Gln Ile Ser Gly Met Gly His Cys885 890 895

ggc gat ggc acg gga gea tcg tac ate ggc cag gga tat ggc acg tac 2736

Gly Asp Gly Thr Gly Ala Ser Tyr Ile Gly Gln Gly Tyr Gly Thr Tyr900 905 910

acc tcc aag gcg ccc caa gtc aac ctg ctg cgc acg atg gtg gac tgg 2784Thr Ser Lys Ala Pro Gln Val Asn Leu Leu Arg Thr Met Val Asp Trp915 920 925

gtg gaa aac gga aag gcg ccc gag tat atg ccg ggc aac aag ctc aac 2832

Val Glu Asn Gly Lys Ala Pro Glu Tyr Met Pro Gly Asn Lys Leu Asn930 935 940

gcg aac ggg tca att gag tac atg cgc aag cac tgc cgg tat ccg aag 2880

Ala Asn Gly Ser Ile Glu Tyr Met Arg Lys His Cys Arg Tyr Pro Lys

945 950 955 960

cat aac att cac acg ggg ccg ggt aac tac acc gat cct aac tcc tgg 2928

His Asn Ile His Thr Gly Pro Gly Asn Tyr Thr Asp Pro Asn Ser Trp965 970 975

act tgc gta 2937

Thr Cys Val

<210> 34<211> 979

<213> Seqüência àrtifictal

<221>

<223> Construção Sintética

<400

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

GlyThr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Gla Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly. Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro ;Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly.260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Ala Thr Asp Pro Phe465 470 475 480

Gln Ser Arg' Cys Asn Glu Phe Gln Asn Lys Ile Asp Ile Ala Asn Val485 490 495

Thr Val Arg Ser Val Ala Tyr Val Ala Ala Gly Gln Asn lie. Ser Gln500 505 510

Ala Glu Val Ala Ser Val Cys Lys Ala Ser Val Gln Ala Ser Val Asp515 520 525

Leu Cys Arg Val Thr Met Asn Ile Ser Thr Ser Asp Arg Ser His Leu530 535 540

Trp Ala Glu Ala Trp Leu Pro Arg Asn Tyr Thr Gly Arg Phe Val Ser545 550 555 560

Thr Gly Asn Gly Gly Leu Ala Gly Cys Val Gln Glu Thr Asp Leu Asn565 570 575

Phe Ala Ala Asn Phe Gly Phe Ala Thr Val Gly Thr Asn Gly Gly His580 585 590

Asp Gly Asp Thr Ala Lys Tyr Phe Leu Asn Asn Ser Glu Val Leu Ala595 600 605

Asp Phe Ala Tyr Arg Ser Val His Glu Gly Thr Val Val Gly Lys Gln610 615 620

Lea Thr Gln Leu Phe Tyr Asp Glu Gly Tyr Asn Tyr Ser Tyr Tyr Leu625 630 635 640

Gly Cys Ser Thr Gly Gly Arg Gln Gly Tyr Gln Gln Val Gln Arg Phe645 650 655

Pro Asp Asp Tyr Asp Gly Val Ile Ala Gly Ser Ala Ala Met Asn Phe660 665 670

Ile Asn Leu Ile Ser Trp Gly Ala Phe Leu Trp Lys Ala Thr Gly Leu675 680 685

Ala Asp Asp Pro Asp Phe Ile Ser Ala Asn Leu Trp Ser Val Ile His690 695 700

Gln Glu Ile Val Arg Gln Cys Asp Leu Val Asp Gly Ala Leu Asp Gly705 710 715 720

IleIle Glu Asp Pro Asp Phe Cys Ala Pro Val Ile Glu Arg Leu Ile725 730 735

Cys Asp Gly Thr Thr Asn Gly Thr Ser Cys Ile Thr Gly Ala Gln Ala

740 745 750

Ala Lys Val Asn Arg Ala Leu Ser Asp Phe Tyr Gly Pro Asp Gly Thr755 760 765

Val Tyr Tyr Pro Arg Leu Asn Tyr Gly Gly Glu Ala Asp Ser Ala Ser770 775 780

Leu Tyr Phe Thr Gly Ser Met Tyr Ser Arg Thr Glu Glu Trp Tyr. Lys785 790 795 800

Tyr Val Val Tyr Asn Asp Thr Asn Trp Asn Ser Ser Gln Trp Thr Leu805 810 815

Glu Ser Ala Lys Leu Ala Leu Glu Gln Asn Pro Phe Asn IleGln Ala820 825 830

Phe Asp Pro Asn Ile Thr Ala Phe Arg Asp Arg Gly Gly Lys Leu Leu835 840 845

Ser Tyr His Gly Thr Gln Asp Pro Ile Ile Ser Ser Thr Asp Ser Lys850 855 860Leu Tyr Tyr Arg Arg Val Ala Asn Ala Leu Asn Ala Ala Pro Ser Glu865 870 875 880

Leu Asp Glu Phe Tyr Arg Phe Phe Gln Ile Ser Gly Met Gly His Cys885 890 895

Gly Asp Gly Thr Gly Ala Ser Tyr Ile Gly Gln Gly Tyr Gly Thr Tyr900 905 910

Thr Ser Lys Ala Pro Gln Val Asn Leu Leu Arg Thr Met Val Asp Trp915 920 925

Val Glu Asn Gly Lys Ala Pro Glu Tyr Met Pro Gly Asn Lys Leu Asn930 935 940

Ala Asn Gly Ser Ile Glu Tyr Met Arg Lys His Cys Arg Tyr Pro Lys945 950 955 960

His Asn Ile His Thr Gly Pro Gly Asn Tyr Thr Asp Pro Asn Ser-Trp' 965 970 975

Thr Cys Val

<210> 35

<211> 3075

<212> DNA

<213> Seqüência artificial

<220> Proteina de fusao

<223>

<220>

<221> CDS

<222> (1)..(3075)

<4 00> 35

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aacAsp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tca 192Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser ·>50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 . 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag 288

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc age att gcc gea tcc agttgc gga tcg tgg acc ctc 336

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct.aat gat gac aca tcc 384

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 432

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc ,atg tat cca gag gtc cat cac gta tcc age aac 480

Cys Lys Ser Gly Thr .Met Tyr Pro Glu Val His His Val Ser Ser Asn.145 150 .155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc-et,a acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 576

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser VaL180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 . 200 205

tgt aca gcg tat.ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala. Ala Pro Asn Gly Asp Tyr Tyr Thr.Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asri Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat catPro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His

912290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly. Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat etc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 105 6

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pró Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val-Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr jPhe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 ' 455 460

tac att gac a.tt ggt gtg cag ttt age cag aat ggc tcg act tac tcc 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

agt gga tet tet tcg ggg tcg ggg tet age tcc age tcg agt tcg act 1488

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

acc act aag gcc act tcg acg acc ttg aag act acc tcg acc acc age 1536

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

agt gga age agt tcg aca tcg gcg gcg gcg acc gac ccc ttc c.ag tcg 1584

Ser Gly Ser Ser Ser Thr. Ser Ala Ala Ala Thr Asp Pro Phe Gln Ser515 520 525

cgg tgc aat gaa ttc cag aac aag ate gac ate gcc aat gtc acc gtcArg Cys Asn Glu Phe Gln Asn Lys Ile Asp Ile Ala Asn Val Thr Val530 535 540

1632aga tcg gtc gca tac gtt gct gct gga cag aac ate tcc caa gcg gag 1680Arg Ser Val Ala Tyr Val Ala Ala Gly Gln Asn Ile Ser Gln Ala Glu545 550 555 560

gtc gcc tcc gtg tgt aaa gca tcg gtt caa gcc agt gtc gac ctg tgc 1728Val Ala Ser Val Cys Lys Ala Ser Val Gln Ala Ser Val Asp Leu Cys565 570 575

cgg gta acc atg aac ate tcg acg tcg gat cgc age cat ctg tgg gct 1776Arg Val Thr Met Asn Ile Ser Thr Ser Asp Arg Ser His Leu Trp Ala580 585 590

gag gcc tgg ctc cca aga aat tat acc ggt cgc ttc gtg age acg ggg 1824Glu Ala Trp Leu Pro Arg Asn Tyr Thr Gly Arg Phe Val Ser Thr Gly595 600 605

aat gga ggt cta gcc ggc tgt gtc caa gaa acg gac ctc aac ttt gca 1872Asn Gly Gly Leu Ala Gly Cys Val Gln Glu Thr Asp Leu Asn Phe Ala610 615 620

gcc aac ttt ggt ttc gct acc gtg ggc acc aac ggt gga cat gac ggg 1920Ala Asn Phe Gly Phe Ala Thr Val Gly Thr Asn Gly Gly His Asp Gly625 630 635 640

gac acg gcc aaa tac ttc ctc aac aac tcg gag gtt ctg gcc gat ttt 1968Asp Thr Ala Lys Tyr Phe Leu Asn Asn Ser Glu Val Leu Ala Asp Phe645 650 655

gcc tat cgc tca gtg cac gaa ggg acc gtg gtg ggt aag caa cta act 2016Ala Tyr Arg Ser Val His Glu Gly Thr Val Val GlyLys-Gln Leu Thr660 665 670

caa ttg ttt tat gac gag gga tac aac tac tcc tac tat ttg ggt tgc 2064Gln Leu Phe Tyr Asp Glu Gly Tyr Asn Tyr Ser Tyr Tyr Leu.Gly Cys675 680 685

tcc acc gga ggc cgc caa ggc tac cag caa gtc caa cgg ttt ccc gac 2112Ser Thr Gly Gly Arg Gln Gly Tyr Gln Gln Val Gln Arg Phe Pro Asp690 695 700

gac tat gac gga gtg att gcg ggc tcc.gca gcg atg aac ttt ate aac 2160Asp Tyr Asp Gly Val Ile Ala Gly Ser Ala Ala Met Asn Phe Ile Asn705 710 715 720

ctg ate tcc tgg ggg gcc ttc ttg tgg aag gcg acg ggg tta gcg gat 2208Leu Ile Ser Trp Gly Ala Phe Leu Trp Lys Ala Thr Gly Leu Ala Asp725 730 735

gat cca gac ttt ate tet gca aac ctg tgg tcc gta ate cac cag gag 2256Asp Pro Asp Phe Ile Ser Ala Asn Leu Trp Ser Val Ile His Gln Glu740 745 750

att gtt cgt cag tgc gac ctg gtc gat ggg gct ctg gat gga ate ate 2304Ile Val Arg Gln Cys Asp Leu Val Asp Gly Ala Leu Asp Gly Ile Ile755 760 765

gaa gac cct gat ttc tgt gct cca gtc ate gag cgc ttg ate tgc gac 2352Glu Asp Pro Asp Phe Cys Ala Pro Val Ile Glu Arg Leu Ile Cys Asp770 775 780ggg act acc aac ggc acc tct tgt ate acg gga gcc cag gea gea aag 2400

Gly Thr Thr Asn Gly Thr Ser Cys Ile Thr-Gly Ala Gln Ala Ala Lys785 790 795 800

gtc aac cgg gcc ttg agt gac ttc tat ggc ccc gac ggg aca gtg tac 2448

Val Asn Arg Ala Leu Ser Asp Phe Tyr Gly Pro Asp Gly Thr Val Tyr805 810 815

tac ccg cgc ctg aac tat ggg ggt gag gcc gac tcg gct tcc ctg tac 2496

Tyr Pro Arg Leu Asn Tyr Gly Gly Glu Ala Asp Ser Ala Ser Leu Tyr820 825 830 ·

ttc acg ggg tcg atg tac age cgt acg gag gaa tgg tac aaa tat gtg 2544

Phe Thr Gly Ser Met Tyr Ser Arg Thr Glu Glu Trp Tyr Lys Tyr Val835 840 845

gtc tat aac gac acc aac tgg aac tcc age cag tgg acg ctg gag agt 2592

Val Tyr Asn Asp Thr Asn Trp Asn Ser Ser Gln Trp Thr Leu Glu Ser850 855 860

gcc aag ctg gcc ctg gag cag aat ccg ttc aat ate cag gcg ttt gat 2640

Ala Lys Leu Ala Leu Glu Gln Asn Pro Phe Asn Ile Gln Ala Phe Asp865 870 875 880

ccc aac ate acg gcc ttc cgg gac cgg ggt ggc aag ctg ctg tcc tac 2688

Pro Asn Ile Thr Ala Phe Arg Asp Arg Gly Gly Lys Leu Leu Ser Tyr885 890 895

cac ggc acg cag gat ccc att ate age tcc acg gat age aag ctc tac 2736His Gly Thr Gln Asp Pro Ile Ile Ser Ser Thr Asp Ser Lys Leu Tyr900 905 910

tac cga cgg gta gcg aat gcc ctg aat gcc gcg ccg tcc gag cta gat 2784

Tyr Arg Arg Val Ala Asn Ala Leu Asn Alá Ala Pro Ser Glu Leu Asp915 920 925

gag ttc tat cgg ttc ttc cag ate tcc ggc atg ggc cac tgt ggc gat 2832

Glu Phe Tyr Arg Phe Phe Gln Ile Ser Gly Met Gly His Cys Gly Asp930 935 940

ggc acg gga gea tcg tac ate ggc cag gga tat ggc acg tac acc tcc 2880

Gly Thr Gly Ala Ser Tyr Ile Gly Gln Gly Tyr Gly Thr Tyr Thr Ser945 950 955 960

aag gcg ccc caa gtc aac ctg ctg cgc acg atg gtg gac tgg gtg gaa 2928

Lys Ala Pro Gln Val Asn Leu Leu Arg Thr Met Val Asp Trp Val Glu965 970 975

aac gga aag gcg ccc gag tat atg ccg ggc aac aag ctc aac gcg aac 2976

Asn Gly Lys Ala Pro Glu Tyr Met Pro Gly Asn Lys Leu Asn Ala Asn980 985 990

ggg tca att gag tac atg cgc aag cac tgc cgg tat ccg aag cat aac 3024Gly Ser Ile Glu Tyr Met Arg Lys His Cys Arg Tyr Pro Lys His Asn995 1000 1005

att cac acg ggg ccg ggt aac tac acc gat cct aac tcc tgg act 3069

Ile His Thr Gly Pro Gly Asn Tyr Thr Asp Pro Asn Ser Trp Thr1010 1015 1020

tgc gta

3075Cys Val1025

<210> 36

<211> 1025

<212> PRT

< 213 > Seqüência: artificial

<220>

<223> "Construção^Sintética

<400> 36

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Vai. Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 4 0 4 5

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr .Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Ash Ser,Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr 'Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln8 5 90 95

Ser Pro Tyr Pro Ser íle Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro.Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Il.e Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Ar.g Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln34b 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly,Gly355 360 365

Pro Tyr Tyr' Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430Gly Ile Arg Leu Thr Ser Pro Thr Gly Gla Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser.-Thr485 490 495

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr 'Ser500 505 510

Ser Gly Ser Ser Ser Thr Ser Ala Ala Ala Thr Asp Pro Phe Gln Ser515 .520 525

Arg Cys Asn Glu Phe Gln Asn Lys Ile Asp Ile Ala Asn Val Thr Val530 535 540

Arg Ser Val Ala Tyr Val Ala Ala Gly Gln Asn Ile Ser Gln Ala Glu545 550 555 560

Val Ala Ser Val Cys Lys Ala Ser Val Gln Ala Ser Vai, Asp Leu Cys5 65 57 0 ' 57.5

Arg Val Thr Met Asn Ile Ser Thr Ser Asp Arg Ser His Leu Trp Ala580 585 590

Glu Ala Trp Leu Pro Arg Asn Tyr Thr Gly Arg Phe Val Ser Thr Gly595 600 605

Asn Gly Gly Leu Ala Gly Cys Val Gln Glu Thr Asp Leu Asn Phe Ala610 615 620

Ala Asn Phe Gly Phe Ala Thr Val Gly. Thr Asn Gly Gly His Asp Gly625 630 635 640

Asp Thr Ala Lys Tyr Phe Leu Asn Asn Ser Glu Val Leu Ala Asp Phe645 650 655

Ala Tyr Arg Ser Val His Glu Gly Thr Val Val Gly Lys Gln Leu Thr660 665 670

Gln Leu Phe Tyr Asp Glu Gly Tyr Asn Tyr Ser Tyr Tyr Leu Gly Cys675

680

685

Ser Thr Gly Gly Arg Gln Gly Tyr Gln Gln Val Gln Arg Phe Pro Asp690 695 700

Asp Tyr Asp Gly Val Ile Ala Gly Ser Ala Ala Met Asn Phe Ile Asn705 710 715 720

Leu Ile Ser Trp Gly Ala Phe Leu Trp Lys Ala Thr Gly Leu Ala Asp725 730 735

Asp Pro Asp Phe Ile Ser Ala Asn Leu Trp Ser Val Ile His Gln Glu740 745 750

Ile Val Arg Gln Cys Asp Leu Val Asp Gly Ala Leu Asp Gly Ile Ile755 760 765

Glu Asp Pro Asp Phe Cys Ala Pro Val Ile Glu Arg Leu Ile Cys Asp770 775 780

Gly Thr Thr Asn Gly -Thr Ser Cys Ile Thr Gly Ala Gln Ala AlajrLys785 790 795 800

Val Asn Arg Ala Leu Ser Asp Phe Tyr Gly Pro Asp Gly Thr Val Tyr805 810 815

Tyr Pro Arg Leu Asn Tyr Gly Gly Glu Ala Asp Ser Ala Ser Leu Tyr820 825 830

Phe Thr Gly Ser Met Tyr Ser Arg Thr Glu Glu Trp Tyr Lys Tyr Val835 840 845

Val Tyr Asn Asp Thr Asn Trp Asn Ser Ser Gln Trp Thr Leu Glu Ser850 855 860

Ala Lys Leu Ala Leu Glu Gln Asn Pro Phe Asn Ile Gln Ala Phe Asp865 870 875 880

Pro Asn Ile Thr Ala Phe Arg Asp Arg Gly Gly Lys Leu Leu Ser Tyr885 890 895

His Gly Thr Gln Asp Pro Ile Ile Ser Ser Thr Asp Ser Lys Leu Tyr900 905 910

Tyr Arg Arg Val Ala Asn Ala Leu Asn Ala Ala Pro Ser Glu Leu Asp915 920 925Glu Phe Tyr Arg Phe Phe Gln Ile Ser Gly Met Gly His Cys Gly Asp930 935 940

Gly Thr Gly Ala Ser Tyr Ile Gly Gln Gly Tyr Gly Thr Tyr Thr Ser945 950 955 960

Lys Ala Pro Gln Val Asn Leu Leu Arg Thr Met Val Asp Trp Val Glu965 970 975

Asn Gly Lys Ala Pro Glu Tyr Met Pro Gly Asn Lys Leu Asn Ala Asn980 985 990

Gly Ser Ile Glu Tyr Met Arg Lys995 1000

His Cys Arg Tyr Pro Lys His Asn1005

Ile His Thr Gly Pro Gly Asn Tyr Thr Asp Pro Asn Ser Trp Thr1010 1015 1020

Cys Val1025

<210>>211>

<213>

<22Ò>*<223>

37

1989DNA

Seqüência artificial

Proteí na de fusão

<220><221><222>

CDS

(1) - · (1989)

<400> 37

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg

Gln Gln Asn Cys Ala .Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

96

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 144

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tca 192

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag 288

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc age att gcc gea tcc agt tgc gga tcg tgg acc ctc 336

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc stgc cca tca tat tgt gct aat gat gac aca tcc 384

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 432

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 480

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 576

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val .180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg.tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320 ,

att cat ctc gac ctg tca gac att gcc atgggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln. 340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc -gea gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 12 4 8

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ,ttc act cct ccg gcc aca ggt.gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly- Asp Pro Asn ~Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat tcg acc ccg age tcg 1440

Tyr Ile Asp Ile ;Gly Val Gln Phe Ser Gln Asn Ser Thr Pro Ser Ser465 470 475 480

acc ggc gag aac aac ggc ttc tac tac tcc ttc tgg acc gac ggc ggt 1488

Thr Gly Glu Asn Asn Gly Phe Tyr Tyr Ser Phe Trp Thr Asp Gly Gly485 490 495

gga gac gtg acc tac acc aac gga gat gct ggt gcc tac act gtt gag 1536

Gly Asp Val Thr Tyr Thr Asn Gly Asp Ala Gly Ala Tyr Thr Val Glu500 505 510

tgg tcc aac gtg ggc aac ttt gtc ggt gga aag ggc tgg aac ccc gga 1584

Trp Ser Asn Val Gly Asn Phe Val Gly Gly Lys Gly Trp Asn Pro Gly515 520 525

agt gcg cag gac ate acc tac age ggc acc ttc acc cct age ggc aac 1632

Ser Ala Gln Asp Ile Thr Tyr Ser Gly Thr Phe Thr Pro Ser Gly Asn530 535 540

ggc tac ctc tcc gtc tat ggc tgg acc act gac cct ctg ate gag tacGly Tyr Leu Ser Val Tyr Gly Trp Thr Thr Asp Pro Leu Ile Glu Tyr545 550 555 560

1680tac ate gtc gag tet tac ggc gac tac aac ccc ggc agt gga ggc acgTyr Ile Val Glu Ser Tyr Gly Asp Tyr Asn Pro Gly Ser Gly Gly Thr565 570 575

tac aag ggc acc gtc acc tcg gac gga tcc gtt tac gat ate tac acgTyr Lys Gly Thr Val Thr Ser Asp Gly Ser Val Tyr Asp Ile Tyr Thr580 585 590

gct acc cgt acc aat gct gct tcc att cag gga acc gct acc ttc actAla Thr Arg Thr Asn Ala Ala Ser Ile Gln Gly Thr Ala Thr Phe Thr595 600 605

cag tac tgg tcc gtt cgc cag aac aag aga gtt ggc gga acc gtt accGln Tyr Trp Ser Vai.Arg Gln Asn Lys Arg Val Gly Gly Thr Val Thr610 615 620

acc tcc aac cac ttc aat gct tgg gct aag ctg gga atg aac ctg ggtThr Ser Asn His Phe Asn Ala Trp Ala Lys Leu Gly Met Asn Leu Gly625 630 635 640

act cac aac tac cag ate gtg gct acc gag ggt tac cag age agt ggaThr His Asn Tyr Gln Ile Val Ala Thr Glu Gly Tyr Gln Ser Ser Gly645 650 655

tet tcg tcc ate act gtt cagSer Ser Ser Ile Thr Val Gln660

<210> 38<211> 663<212> .....PRT.....<213> Seqüência artificial<22Ò> <223> Construção:Sintética<400> 38.......

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser GlnSer Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr .Jlet Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu ProiGly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335.Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Al-a385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala·Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Ser Thr Pro Ser.Ser465 470 475 480

Thr Gly Glu Asn Asn Gly Phe Tyr Tyr Ser Phe Trp Thr Asp Gly Gly485 490 495

Gly Asp Val Thr Tyr Thr Asn Gly Asp Ala Gly Ala Tyr Thr Val Glu500 '505 510

Trp Ser Asn Val Gly Asn Phe Val Gly Gly Lys Gly Trp Asn Pro Gly515 520 525

Ser Ala Gln Asp Ile Thr Tyr Ser Gly Thr Phe Thr Pro Ser Gly Asn530 535 540

Gly Tyr Leu Ser Val Tyr Gly Trp Thr Thr Asp Pro Leu Ile Glu Tyr545 550 555 560

Tyr Ile Val Glu Ser Tyr Gly Asp Tyr Asn Pro Gly Ser Gly Gly Thr565 570 575Tyr Lys Gly Thr Val Thr Ser Asp Gly Ser Val Tyr Asp Ile Tyr Thr580 585 590

Ala Thr Arg Thr Asn Ala Ala Ser Ile Gln Gly Thr Ala Thr Phe Thr595 600 605

Gln Tyr Trp Ser Val Arg Gln Asn Lys Arg Val Gly Gly Thr Val Thr610 615 620

Thr Ser Asn His Phe Asn Ala Trp Ala Lys Leu Gly Met Asn Leu Gly625 630 635 640

Thr His Asn Tyr Gln Ile Val Ala Thr Glu Gly Tyr Gln Ser Ser Gly645 650 655

Ser Ser Ser Ile Thr Val Gln660

<210> 39<21l> 2127<212> DNA

<213> Seqüência artificial

<220>

<223> Proteína de fusão

<220>

<221> CDS<222> (1) (2127)

<400> 39

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg 48

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp

1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aat 96

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc. cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 14 4

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tca 192

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cagSer Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln

28885 90 95

tct cct tac ccc age att gcc gea tcc agt tgc gga tcg tgg acc ctc 336

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 432

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 480

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 ' 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 . 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 57 6

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ct.t ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc ,gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly.Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro ^Gly Ala Leu Asp Asn'Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa- aca aag ccc gat ggg acc gat tat- gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 . 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aatIle His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

1008gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caaGly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

1056

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga gggCys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

1104

cct tac tat ttt gct etc acg gea gtc aac acc aac gga ccg ggc tcaPro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

1152

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gccVal Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

1200

P

O

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 12 4 8

Leu. Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr40.5 410 415 '

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 " 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cagGly Ile Arg Leu Thr :Ser Pro Thr. Gly Glu Gln Ile Val Asn Glu Gln435 440 445

1344

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tacAla Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 '460

1392

tac att gac att ggt ;gtg cag ttt age cag aat ggc tcg act tac tccTyr Ile Asp Ile ,Gly'Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr;Ser4 65 470 47.5 480

1440

agt gga tet tet tcg .ggg tcg ggg tet age tcc age tcg agt tcg actSer Gly Ser Ser Ser -Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr;485 490 495

1488

acc act aag gcc act tcg acg acc ttg aag act acc tcg acc acc ageThr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

1536

agt gga age agt tcg aca tcg gcg gcg tcg acc ccg. age tcg acc ggcSer Gly Ser Ser Ser Thr Ser Ala Ala Ser Thr Pro Ser Ser Thr Gly515 520 525

1584

gag aac aac ggc ttc tac tac tcc ttc tgg acc gac ggc ggt gga gacGlu Asn Asn Gly Phe Tyr Tyr Ser Phe Trp Thr Asp Gly Gly Gly Asp530 535 540

1632

gtg acc tac acc aac gga gat gct ggt gcc- tac act gtt gag tgg tccVal Thr Tyr Thr Asn .Gly Asp Ala Gly Ala Tyr Thr Val Glu Trp Ser545 550 555 560

1680

aac gtg ggc aac ttt gtc ggt gga aag ggc tgg aac ccc gga agt gcgAsn Val Gly Asn Phe Val Gly Gly Lys Gly Trp Asn Pro Gly Ser Ala565 570 575

1728cag gac ate acc tac age ggc acc ttc acc cct age ggc aac ggc tacGln Asp Ile Thr Tyr Ser Gly Thr Phe Thr Pro Ser Gly Asn Gly Tyr580 585 590

etc tcc gtc tat ggc tgg acc act gac cct ctg ate gag tac tac ateLeu Ser Val Tyr Gly Trp Thr Thr Asp Pro Leu Ile Glu Tyr Tyr Ile595 600 605

gtc gag tet tac ggc gac tac aac ccc ggc agt gga ggc acg tac aagVal Glu Ser Tyr Gly Asp Tyr Asn Pro Gly Ser Gly Gly Thr Tyr Lys610 615 620

ggc acc gtc acc tcg gac gga tcc gtt tac gat ate tac acg gct accGly Thr Val Thr Ser Asp Gly Ser Val Tyr Asp Ile Tyr Thr Ala Thr625 630 635 640

cgt acc aat gct gct tcc att cag gga acc gct acc ttc act cag tacArg Thr Asn Ala Ala Ser Ile Gln Gly Thr Ala Thr Phe Thr Gln Tyr645 650 655

tgg tcc gtt cgc cag aac aag aga gtt ggc gga acc gtt acc acc tccTrp Ser Val Arg Gln Asn Lys Arg Val. Gly Gly Thr Val Thr Thr Ser660 665 670

aac cac ttc aat gct tgg gct aag ctg gga atg aac ctg ggt act cacAsn His Phe Asn Ala Trp Ala Lys Leu Gly Met Asn Leu Gly Thr His675 680 685

aac tac cag ate gtg gct acc gag ggt tac cag age agt gga tet tcgAsn Tyr Gln Ile Val Ala Thr Glu Gly Tyr Gln Se.r Ser Gly Ser Ser690 695 700

tcc ate act gtt cagSer Ile Thr Val Gln705

<210>. 40<211> 709<212> PRT..

<213> Seqüência artificiar '

<2 2 3> Construção Sintética

<400> 40"

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser.Ser Ala Ser Ser50 55 60Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys LysSer Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val AspSer Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln. Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

Ser Gly Ser Ser Ser Thr Ser Ala Ala Ser Thr Pro Ser Ser Thr Gly515 520 525

Glu Asn Asn Gly Phe Tyr Tyr Ser Phe Trp Thr Asp Gly Gly Gly Asp530 535 540Val Thr Tyr Thr Asn Gly Asp Ala Gly Ala Tyr Thr Val Glu Trp Ser545 550 555 560

Asn Val Gly Asn Phe Val Gly Gly Lys Gly Trp Asn Pro Gly Ser Ala565 570 575

Gln Asp Ile Thr Tyr Ser Gly Thr Phe Thr Pro Ser Gly Asn Gly Tyr580 585 590

Leu Ser Val Tyr Gly Trp Thr Thr Asp Pro Leu Ile Glu Tyr Tyr Ile595 600 605

Val Glu Ser Tyr Gly Asp Tyr Asn Pro Gly Ser Gly Gly Thr Tyr Lys610 615 620

Gly Thr Val Thr Ser Asp Gly Ser.Val Tyr Asp Ile Tyr Thr Ala Thr625 630 635 640

Arg Thr Asn Ala Ala Ser Ile Gln Gly Thr Ala Thr Phe Thr Gln Tyr645 650 655

Trp Ser Val Arg Gln Asn Lys Arg Val Gly Gly Thr Val Thr Thr Ser660 665 670

Asn His Phe Asn Ala Trp Ala Lys Leu Gly Met Asn Leu Gly Thr His675 680 685

Asn Tyr Gln Ile Val Ala Thr Glu Gly Tyr Gln Ser Ser Gly Ser Ser690 695 700

Ser Ile Thr Val Gln705

<210> 41

<211> 2919

<212 > DNA

<213> Seqüência artificial

<220>

<223 > Proteína de fusão

<220>

<221> CDS<222> (1)..(2919)

<400> 41

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp15 10 15tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aacAsp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gea tcc tcaGly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gctSer Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cagSer Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc a.gc att gcc gea tcc agt tgc gga tcg tgg acc ctcSer Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tccVal Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gacGlu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aacCys Lys Ser GlyThr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggcGlu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgti ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gttGly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct tttThr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc cttCys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tggArg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgcSer Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

144

192

240

288

336

384

432

480

528

576

624

672

720

768att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc ggaIle Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

816

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgcGlu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

864

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat catPro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

912

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac ageCys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

960

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aatIle His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

1008

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caaGLy Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

1056

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga gggCys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly.355 3 60 3 65

1104

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tcaPro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn. Gly Pro Gly Ser370 375 380

1152

gtc acc aaa ate gàg ate aag ggc gea gac acé gac aac tgg gtt gccVal Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

1200

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tatLeu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

1248

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gttGly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

1296

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cagGly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

1344

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tacAla Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

1392

tac att gac att ggt gtg cag ttt age cag aat cag tcg gcc tgc actTyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Ser Ala Cys Thr465 470 475 480

1440

ctc caa tcg gag act cac ccg cct ctg aca tgg cag aaa tgc tcg tetLeu Gln Ser Glu Thr His Pro Pro Leu Thr Trp Gln Lys Cys Ser Ser485 490 495

1488

ggt ggc acg tgc act caa cag aca ggc tcc gtg gtc ate gac gcc aac 1536Glv Gly Thr Cys Thr Gln Gln Thr Gly Ser Val Val Ile Asp Ala Asn 500 505 510

tgg cgc tgg act cac gct acg aac age age acg aac tgc tac gat ggc 1584

Trp Arg Trp Thr His Ala Thr.Asn Ser Ser Thr Asn Cys Tyr Asp Gly515 520 525

aac act tgg age tcg acc cta tgt cct gac aac gag acc tgc gcg aag 1632

Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp Asn Glu Thr Cys' Ala Lys530 535 540

aac tgc tgt ctg gac ggt gcc gcc ta.c gcg tcc acg tac gga gtt acc 1680

Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala Ser Thr Tyr Gly Val Thr545 550 555 560

acg age ggt aac age ctc tcc att ggc ttt gtc acc cag tet gcg cag 1728

Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe Val Thr Gln Ser Ala Gln565 570 575

aag aac gtt ggc gct cgc ctt tac ctt atg gcg age gac acg acc tac 1776

Lys Asn Val Gly Ala Arg Leu Tyr Leu Met Ala Ser Asp Thr Thr Tyr580 585 590

caggaa ttc acc ctg ctt ggc aac gag ttc tet ttc gat gtt gat gtt 1824

Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe Ser Phe Asp Val Asp Val595 600 605

tcg cag ctg ccg tgc ggc ttg aac gga gct ctc tac ttc gtg tcc atg 1872

Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala Leu Tyr Phe Val Ser Met610 615 620

gac gcg gat ggt ggc gtg age aag tat ccc acc aac acc gct ggc gcc 1920

Asp Ala Asp Gly Gly Val Ser:Lys Tyr Pro Thr Asn Thr Ala Gly Ala625 630 635 640

aag tac ggc acg ggg tac tgt gac age cag tgt ccc cgc gat ctg aag 1968

Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln Cys Pro Arg Asp Leu Lys645 650 655

ttc ate aat ggc cag gcc aac gtt gag ggc tgg gag ccg tca tcc aac 2016

Phe Ile Asn Gly Óln Ala Asn Val Glu Gly Trp Glu Pro Ser Ser Asn660 665 670

aac gcg aac acg ggc att gga gga cac gga age tgc tgc tet gag atg 2064

Asn Ala Asn Thr Gly Ile Gly Gly His Gly Ser Cys Cys Ser Glu Met675 680 685

gat ate tgg gag gcc aac tcc ate tcc gag gct ctt acc ccc cac cct 2112

Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu Ala Leu Thr Pro His Pro690 695 700

tgc acg act gtc ggc cag gag ate tgc gag ggt gat ggg tgc ggc gga 2160

Cys Thr Thr Val Gly Gln Glu Ile Cys Glu Gly Asp Gly Cys Gly Gly705 710 715 720

act tac tcc gat aac aga tat ggc ggc act tgc gat ccc gat ggc tgc 2208

Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr Cys Asp Pro Asp Gly Cys725 730 735

gac tgg aac cca tac cgc ctg ggc aac acc age ttc tac ggc cct ggcAsp Trp Asn Pro Tyr Arg Leu Gly Asn Thr Ser Phe Tyr Gly Pro Gly

2256740 745 750

tca age ttt acc ctc gat acc acc aag aaa ttg acc gtt gtc acc cag 2304

Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys Leu Thr Val Val Thr Gln755 760 765

ttc gag acg tcg ggt gcc ate aac cga tac tat gtc cag aat ggc gtc 2352

Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr Tyr Val Gln Asn Gly Val770 775 780

act ttc cag cag ccc aac gcc gag ctt ggt agt tac tet ggc aac gag 2400

Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly Ser Tyr Ser Gly Asn Glu785 790 795 800

ctc aac gat gat tac tgc aca gct gag gag gea gaa ttc ggc gga tcc 2448

Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu Ala Glu Phe Gly Gly Ser805 810 815

tet ttc tca gac aag ggc ggc ctg act cag ttc aag aag gct acc tet 2496

Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln Phe Lys Lys Ala Thr Ser820 825 830

ggc ggc atg gtt ctg gtc atg agt ctg tgg gat gat tac tac gcc aac 25 4

Gly Gly Met Val Leu Val Met Ser Leu Trp Asp Asp Tyr Tyr Ala Asn835 840 845

atg ctg tgg ctg gac tcc acc tac ccg aca aac gag acc tcc tcc aca 2592

Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr Asn Glu Thr Ser Ser Thr850 855 860

ccc ggt gcc gtg cgc gga age tgc tcc acc age tcc ggt gtc cct gct 2640

Pro Gly Ala Val Arg Gly Ser Cys Ser Thr Ser Ser Gly Val Pro Ala865 870 875 880

cag gtc gaa tet cag tet ccc aac gcc aag gtc acc ttc tcc aac ate 2688

Gln Val Glu Ser Gln Ser Pro Asn Ala Lys Val Thr Phe Ser Asn Ile885 890 895

aag ttc gga ccc att ggc age acc ggc aac cct age ggc ggc aac cct 2736

Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn Pro Ser Gly Gly Asn Pro900 905 910

ccc ggc gga aac ccg cct ggc acc acc acc acc cgc cgc cca gcc act 2784

Pro Gly Gly Asn Pro Pro Gly Thr Thr Thr Thr Arg Arg Pro Ala Thr915 920 925

acc act gga age tet ccc gga cct acc cag tet cac tac ggc cag tgc 2832

Thr Thr Gly Ser Ser Pro Gly Pro Thr Gln Ser His Tyr Gly Gln Cys930 935 940

ggc ggt att ggc tac age ggc ccc acg gtc tgc gcc age ggc aca act 2880

Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val Cys Ala Ser Gly Thr Thr945 950 955 960

tgc' cag gtc ctg aac cct tac tac tet cag tgc ctg taa 2919

Cys Gln Val Leu Asn Pro Tyr Tyr Ser Gln Cys Leu965 970

<210> 42<211> 972<212> PRT

<213> Seqüência artificial

<220>

<223> Construção Sintética

<400> 42

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp

1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr 'Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr PheiAla Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln He Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Ser Ala Cys Thr465 470 475 480

Leu Gln Ser Glu Thr His Pro Pro Leu Thr Trp Gln Lys Cys Ser Ser485 490 495

Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser Val Val Ile Asp Ala Asn500 505 510

Trp Arg Trp Thr His Ala Thr Asn Ser Ser Thr Asn Cys Tyr Asp Gly515 520 525

Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp Asn Glu Thr Cys Ala Lys530 535 540

Asn Cys Cys-Leu Asp Gly Ala Ala Tyr Ala Ser Thr Tyr Gly Val Thr545 550 555 560

Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe Val Thr Gln Ser Ala Gln565 570 575

Lys Asn Val Gly Ala Arg Leu Tyr Leu Met Ala Ser Asp Thr Thr Tyr580 585 590

Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe Ser Phe Asp Val Asp Val595 600 605

Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala Leu Tyr Phe Val Ser Met610 615 620

Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro Thr Asn Thr Ala Gly Ala625 630 635 640

Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln Cys Pro Arg Asp Leu Lys645 650 655

Phe Ile Asn Gly Gln Ala Asn Val Glu Gly Trp Glu Pro Ser Ser Asn660 665 670

Asn Ala Asn Thr Gly Ile Gly Gly His Gly Ser Cys Cys Ser Glu Met675 680 685

Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu Ala Leu Thr Pro His Pro690 695 700Cys Thr Thr Val Gly Gln Glu Ile Cys Glu Gly Asp Gly Cys Gly Gly705 710 715 720

Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr Cys Asp Pro Asp Gly Cys725 730 735

Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr Ser Phe Tyr Gly Pro Gly740 745 750

Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys Leu Thr Val Val Thr Gln755 760 765

Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr Tyr Val Gln Asn Gly Val770 775 780

Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly Ser Tyr Ser Gly Asn Glu785 790 795 800

Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu Ala Glu Phe Gly Gly Ser805 810 815

Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln Phe Lys -Lys Ala Thr Ser820 825 830

Gly Gly Met Val Leu Val Met Ser Leu Trp Asp Asp Tyr Tyr Ala Asn835 840 845

Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr Asn Glu Thr Ser Ser Thr850 855 860

Pro Gly Ala Val Arg Gly Ser Cys Ser Thr Ser Ser Gly Val Pro Ala865 870 875 880

Gln Val Glu Ser Gln885

Lys Phe Gly Pro Ile900

Pro Gly Gly Asn Pro915

Thr Thr Gly Ser Ser930

Ser Pro Asn Ala Lys Val8 90

Gly Ser Thr Gly Asn Pro905

Pro Gly Thr Thr Thr Thr920

Pro Gly Pro Thr Gln Ser935

Thr Phe Ser Asn Ile895

Ser Gly Gly Asn Pro910

Arg Arg Pro Ala Thr925

His Tyr Gly Gln Cys940Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val Cys Ala Ser Gly Thr Thr945 950 955 960

Cys Gln Val Leu Asn Pro Tyr Tyr Ser Gln Cys Leu965 970

fêSSí·

<220><221><222>

<210> 43

<211> 3057

<212> DNA<213>

<223> Proteína de fusão

Seqüência: artificial

CDS

(1)..(3057)

<4 00> 43 ·

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp15 10 15

48

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt t.tt .gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala- Gln Cys Ser Phe Val Asn20 25 30

96

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aacAsp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn/Pro Pro Asn

3545

144

gga aca act tcc tet age ttg gtt tca çggacgtcg tca gca tcc tcaGly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

192

tcc gtc ggc tcg tet tca ccc ggc ggc aac tca cca.act ggc agt gctSer Val Gly Ser: Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 7® 75 80

tcc acc tac aca acc aca" gat aca gct acc gtg gct cct cat tcg cagSer Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

240

288

tet cct tac ccc age att gcc gca tcc agt tgc gga tcg tgg acc ctcSer Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

336

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tccVal Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

384

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gacGlu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

432

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aacCys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

480gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 576Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly -260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro. Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 10.08Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att t.gg ctt cga aat ggc gga ggg 1104Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac' gga ccg ggc tca 1152Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380.

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gccVal Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

1200ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 12 96

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 13 4 4

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat ggc tcg act tac tcc 14 40

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

agt gga tet tet tcg ggg tcg ggg tet age tcc age tcg agt tcg act 1488

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

acc act aag gcc act tcg acg acc ttg aag act acc tcg acc acc age 1536

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

agt gga age agt tcg aca tcg gcg gcg cag tcg gcc tgc act ctc caa 1584

Ser Gly Ser Ser Ser Thr Ser Ala Ala Gln Ser Ala Cys Thr Leu Gln515 520 525

tcg gag act cac ccg cct ctg aca tgg cag aaa tgc tcg tet ggt ggc 1632

Ser Glu Thr His Pro Pro Leu Thr Trp Gln Lys Cys Ser Ser Gly Gly530 535 540

acg tgc act caa cag aca ggc tcc gtg gtc ate gac gcc aac tgg cgc 1680

Thr Cys Thr Gln Gln Thr Gly Ser Val Val Ile Asp Ala Asn Trp Arg545 550 555 560

tgg act cac gct acg aac age age acg aac tgc tac gat ggc aac act 1728

Trp Thr His1 Ala Thr Asn Ser Ser Thr Asn Cys Tyr Asp Gly Asn Thr565 570 575

tgg age tcg acc cta tgt cct gac aac gag acc tgc gcg aag aac tgc 1776

Trp Ser Ser Thr Leu Cys Pro Asp Asn Glu Thr Cys Ala Lys Asn Cys580 585 590

tgt ctg gac ggt gcc gcc tac gcg tcc acg tac gga gtt acc acg age 1824

Cys Leu Asp Gly Ala Ala Tyr Ala Ser Thr Tyr Gly Val Thr Thr Ser595 600 605

ggt aac age ctc tcc att ggc ttt gtc acc cag tet gcg cag aag aac 1872

Gly Asn Ser Leu Ser Ile Gly Phe Val Thr Gln Ser Ala Gln Lys Asn610 615 620

gtt ggc gct cgc ctt tac ctt atg gcg age gac acg acc tac cag gaa 1920

Val Gly Ala Arg Leu Tyr Leu Met Ala Ser Asp Thr Thr Tyr Gln Glu625 630 635 640

ttc acc ctg ctt ggc aac gag ttc tet ttc gat gtt gat gtt tcg cag 1963Phe Thr Leu Leu Gly Asn Glu Phe Ser Phe Asp Val Asp Val Ser Gln^645 650 655

ctg ccg tgc ggc ttg aac gga gct ctc tac ttc gtg tcc atg gac gcg 2016

Leu Pro Cys Gly Leu Asn Gly Ala Leu Tyr Phe Val Ser Met Asp Ala660 665 670

gat ggt ggc gtg age aag tat ccc acc aac acc gct ggc gcc aag tac 2064

Asp Gly Gly Val Ser Lys Tyr Pro Thr Asn Thr Ala Gly Ala Lys Tyr675 680 685

.ggc acg ggg tac tgt gac age cag tgt ccc cgc gat ctg aag ttc ate 2112

Gly Thr Gly Tyr Cys Asp Ser Gln Cys Pro Arg Asp Leu Lys Phe Ile690 695 700

aat ggc cag gcc aac gtt gag ggc tgg gag ccg tca tcc aac aac gcg . 2160Asn Gly Gln Ala Asn Val Glu Gly Trp Glu Pro Ser Ser Asn Asn Ala705 710 715 720

aac acg ggc att gga gga cac gga age tgc tgc tet gag atg gat ate 2208

Asn Thr Gly Ile Gly Gly His Gly Ser Cys Cys Ser Glu Met Asp Ile725 730 735 :

tgg gag gcc aac tcc ate tcc gag gct ctt acc ccc cac cct tgc acg 2256

Trp Glu Ala Asn Ser Ile Ser Glu Ala Leu Thr Pro His Pro Cys Thr740 745 750

act gtc ggc cag gag ate tgc gag ggt gat ggg tgc ggc gga act tac 2304

Thr Val Gly Gln Glu Ile Cys Glu Gly Asp Gly Cys Gly Gly Thr Tyr755 760 765

tcc gat aac aga tat ggc ggc act tgc gat ccc gat ggc tgc gac tgg 2352

Ser Asp Asn Arg Tyr Gly Gly Thr Cys Asp Pro Asp Gly Cys Asp Trp770 775 780

aac cca tac cgc ctg ggc aac acc age ttc tac ggc cct ggc tca age' 2400Asn Pro Tyr Arg Leu Gly Asn Thr Ser Phe Tyr Gly Pro Gly Ser Ser785 790 795 800

ttt acc ctc gat acc acc aag aaa ttg acc gtt gtc acc cag ttc gag 2448

Phe Thr Leu Asp Thr Thr Lys Lys Leu Thr Val Val Thr Gln Phe Glu805 810 815

acg tcg ggt gcc ate aac cga tac tat gtc cag aat ggc gtc act ttc 2496

Thr Ser Gly Ala Ile Asn Arg Tyr Tyr Val Gln Asn Gly Val Thr Phe820 825 830

cag cag ccc aac gcc gag ctt ggt agt tac tet ggc aac gag ctc aac 2544

Gln Gln Pro Asn Ala Glu Leu Gly Ser Tyr Ser Gly Asn Glu Leu Asn835 840 845

gat gat tac tgc aca gct gag gag gea gaa ttc ggc gga tcc tet ttc 2592

Asp Asp Tyr Cys Thr Ala Glu Glu Ala Glu Phe Gly Gly Ser Ser Phe850 855 86Ó

tca' gac aag ggc ggc ctg act cag ttc aag aag gct acc tet ggc ggc 2640

Ser Asp Lys Gly Gly Leu Thr Gln Phe Lys Lys Ala Thr Ser Gly Gly865 870 875 880

atg gtt ctg gtc atg agt ctg tgg gat gat tac tac gcc aac atg ctg 2688

Met Val Leu Val Met Ser Leu Trp Asp Asp Tyr Tyr Ala Asn Met Leu885 890 895

tgg ctg gac tcc acc tac ccg aca aac gag acc tcc tcc aca ccc ggt 2736Trp Leu Asp Ser Thr Tyr Pro Thr Asn Glu Thr Ser Ser Thr Pro Gly900 905 910

gcc gtg cgc gga age tgc tcc acc age tcc ggt gtc cct gct cag gtc 2784Ala Val Arg Gly Ser Cys Ser Thr Ser Ser Gly Val Pro Ala Gln Val915 920 925

gaa tet cag tet ccc aac gcc aag gtc acc ttc tcc aac ate aag ttc 2832Glu Ser Gln Ser Pro Asn Ala Lys Val Thr Phe Ser Asn Ile Lys Phe930 935 940

gga ccc att ggc age acc ggc aac cct age ggc ggc aac cct ccc ggc 2880Gly Pro Ile Gly Ser Thr Gly Asn Pro Ser Gly Gly Asn Pro Pro Gly945 950 955 960

gga aac ccg cct ggc acc acc acc acc cgc cgc cca gcc act acc act 2928Gly Asn Pro Pro Gly Thr Thr Thr Thr Arg Arg Pro Ala Thr Thr Thr965 970 975

gga age tet ccc gga cct acc cag tet cac tac ggc cag tgc ggc ggt 2976Gly Ser Ser Pro Gly Pro Thr Gln Ser His Tyr Gly Gln Cys Gly Gly980 985 990

att ggc tac age ggc ccc acg gtc tgc gcc age ggc aca act tgc cag 3024Ile Gly Tyr Ser Gly Pro Thr Val Cys Ala Ser Gly Thr Thr Cys Gln995 1000 1005

gtc ctg aac cct tac tac tet cag tgc ctg taa 3057Val Leu Asn Pro Tyr Tyr Ser Gln Cys Leu1010 1015

<210> 44<211> 1018<212> PRT<213> Seqüência artificial

<220>

<223> Construção Sintética

<400> 4 4

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 '70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met. Tyr Pro Glu Val His Hls Val Ser Ser Asn145 150 ' 155 ' 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180· 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 ' 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305

310

315

320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gl.y Asp Pro Asn Phe Tyr

450 455 460

Tyr Ile Asp Ile ,Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

Ser Gly Ser Ser Ser Thr Ser Ala Ala Gln Ser Ala Cys Thr Leu Gln515 520 525

Ser Glu Thr His Pro Pro Leu Thr Trp Gln Lys Cys Ser Ser Gly Gly530 535 540

Thr Cys Thr Gln Gln Thr Gly Ser Val Val Ile Asp Ala Asn Trp Arg545 550 555 560Trp Thr His Ala Thr Asn Ser Ser Thr Asn Cys Tyr Asp Gly Asn Thr565 570 575

Trp Ser Ser Thr Leu Cys Pro Asp Asn Glu Thr Cys Ala Lys Asn Cys580 585 590

Cys Leu Asp Gly Ala Ala Tyr Ala Ser Thr Tyr Gly Val Thr Thr Ser595 600 605

Gly Asn Ser Leu Ser Ile Gly Phe Val Thr Gln Ser Ala Gln Lys Asn610 615 620

Val Gly Ala Arg Leu Tyr Leu Met Ala Ser Asp Thr Thr Tyr Gln Glu625 630 635 640

Phe Thr Leu Leu Gly Asn Glu Phe Ser Phe Asp Val Asp Val Ser Gln645 650 655

Leu Pro Cys Gly Leu Asn Gly Ala Leu Tyr Phe Val Ser Met- Asp Ala660 665 670

Asp Gly Gly Val Ser Lys Tyr Pro Thr Asn Thr Ala Gly Ala Lys Tyr675 680 685

Gly Thr Gly Tyr Cys Asp Ser Gln Cys Pro Arg Asp Leu Lys Phe Ile690 695 700

Asn Gly Gln Ala Asn Val Glu Gly Trp Glu Pro Ser Ser Asn Asn Ala705 710 715 720

Asn Thr Gly Ile Gly Gly His Gly Ser Cys Cys Ser Glu Met Asp Ile725 730 735

Trp Glu Ala Asn Ser Ile Ser Glu Ala Leu Thr Pro His Pro Cys Thr740 745 750

Thr Val Gly Gln Glu Ile Cys Glu Gly Asp Gly Cys Gly Gly Thr Tyr755 760 765

Ser Asp Asn Arg Tyr Gly Gly Thr Cys Asp Pro Asp Gly Cys.Asp Trp770 775 780

Asn Pro Tyr Arg Leu Gly Asn Thr Ser Phe Tyr Gly Pro Gly Ser Ser735 790 795 800Phe Thr Leu Asp Thr Thr Lys Lys Leu Thr Val Val Thr Gln Phe Glu805 810 815

Thr Ser Gly Ala Ile Asn Arg Tyr Tyr Val Gln Asn Gly Val Thr Phe820 825 830 .

Gln Gln Pro Asn Ala Glu Leu Gly Ser Tyr. Ser Gly Asn Glu Leu Asn835 840 845

Asp Asp Tyr Cys Thr Ala Glu Glu Ala Glu Phe Gly Gly Ser Ser Phe850 855 860

Ser Asp Lys Gly Gly Leu Thr Gln Phe Lys Lys Ala Thr Ser Gly Gly865 870 875 880

Met Val Leu Val Met Ser Leu Trp Asp Asp Tyr Tyr Ala Asn Met Leu885 890 895

Trp Leu Asp Ser Thr Tyr Pro Thr Asn Glu Thr Ser Ser Thr Pro Gly900 905 910

Ala Val Arg Gly Ser Cys Ser Thr Ser Ser Gly Val Pro Ala Gln Val915 920 925

Glu Ser Gln Ser Pro Asn Ala Lys Val Thr. Phe Ser Asn Ile Lys Phe930 935 940

Gly Pro Ile Gly Ser Thr Gly Asn Pro Ser Gly Gly Asn Pro Pro Gly945 950 955 960

Gly Asn Prò Pro Gly Thr Thr Thr Thr Arg Arg Pro Ala Thr Thr Thr• 965 970 975

Gly Ser Ser Pro Gly Pro Thr Gln Ser His Tyr Gly Gln Cys Gly Gly980 · 985 990

Ile Gly Tyr Ser Gly Pro Thr Val Cys Ala Ser Gly Thr Thr Cys Gln995 1000 1005

Val Leu Asn Pro Tyr Tyr Ser Gln Cys Leu1010 1015

<210> 45

<211> 2919

<212> DNA

<213> Seqüência artificial<220>

<223> Proteína de fusão

<220>

<221> CDS<222> (1)..(2919)

<400> 45

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg 4 8

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys .Gly Gly Ile Gly Trp1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aat 96

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 144

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tca 192

Gly Thr Thr Ser Ser Ser Leu Val·Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 24 0

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag 288

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc a.gc att gcc gca tcc agt tgc gga tcg tgg acc ctc 336

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384

Val Asp Asn Val ,Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 432

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 480

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 57 6

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct tttThr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

624tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gca gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Vai. Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa taç ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr-Asn -Gly Val Ile Pro Thr Arg Tyr Arg Ar-g Val Gln34 0 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg çtt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp' Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gca gtc aac acc· aac gga ccg ggc tca . 11.52Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag atç aag ggc gca gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cagGly Ile Arg Leu Thr Ser Pro Thr Gly GluGln Ile Val Asn Glu Gln435 440 445

1344gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat cag tcg gcc tgc act 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Ser Ala Cys Thr465 470 475 480

ctc caa tcg gag act cac ccg cct ctg aca tgg cag aaa tgc tcg tet 1488

Leu Gln Ser Glu Thr His Pro Pro Leu Thr Trp Gln Lys Cys Ser Ser485 490 495

ggt ggc acg tgc act caa cag aca ggc tcc gtg gtc ate gac gcc aac 1536

Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser Val Val Ile Asp Ala Asn500 505 510

tgg cgc tgg act cac gct acg aac age age acg aac tgc tac gat ggc 1584

Trp Arg Trp Thr His Ala Thr Asn Ser Ser Thr Asn Cys Tyr Asp Gly515 520 525

aac act tgg age tcg acc cta tgt cct gac aac gag acc tgc gcg aag 1632

Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp Asn Glu Thr Cys Ala Lys530 535 540

aac tgc tgt ctg gac ggt gcc gcc tac gcg tcc acg tac gga.gtt acc 1680Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala Ser Thr Tyr Gly Val Thr545 550 555 560·

acg age ggt aac age ctc tcc att ggc ttt gtc acc cag tet gcg cag 1728

Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe Val Thr Gln Ser Ala Gln565 570 575

aag aac gtt ggc gct cgc ctt tac ctt atg gcg age gac acg acc tac 1776

Lys Asn Val Gly Ala Arg Leu Tyr Leu Met Ala Ser Asp Thr Thr Tyr580 585 590

cag gaa ttc acc ctg ctt ggc ãac gag ttc tet ttc gat gtt gat gtt 1824

Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe Ser Phe Asp Val Asp Val595 600 605

tcg cag ctg ccg tgc ggc ttg aac gga gct ctc tac ttc gtg tcc atg 1872

Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala Leu Tyr Phe Val Ser Met610 615 620

gac gcg gat ggt ggc gtg age aag tat ccc acc aac acc gct ggc gcc 1920

Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro Thr Asn Thr'Ala Gly Ala625 630 635 640

aag tac ggc acg ggg tac tgt gac age cag tgt ccc cgc gat ctg aag 1968

Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln Cys Pro Arg Asp Leu Lys645 650 655

ttc ate aat ggc cag gcc aac gtt gag ggc tgg gag ccg tca tcc aac 2016

Phe Ile Asn Gly Gln Ala Asn Val Glu Gly Trp Glu Pro Ser Ser Asn660 665 670

aac gcg aac acg ggc att gga gga cac gga age tgc tgc tet gag atg 2064

Asn Ala Asn Thr Gly Ile Gly Gly His Gly Ser Cys Cys Ser Glu Met675 680 685

gat ate tgg gag gcc aac tcc ate tcc gag gct ctt acc ccc cac cct 2112Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu Ala Leu Thr Pro His Pro690 695 700

tgc acg ac.t gtc ggc cag gag ate tgc gag ggt gat ggg tgc ggc gga 2160

Cys Thr Thr Val Gly Gln Glu Ile Cys Glu Gly Asp Gly Cys Gly Gly705 710 715 720

act tac tcc gat aac aga tat ggc ggc act tgc gat ccc gat ggc tgc 2208

Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr Cys. Asp Pro Asp Gly Cys725 730 735

gac tgg aac cca tac cgc ctg ggc aac acc age ttc tac ggc cct ggc 2256

Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr Ser Phe Tyr Gly Pro Gly740 745 750

tca age ttt acc ctc gat acc acc aag aaa ttg acc gtt gtc acc cag 2304

Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys Leu Thr Val Val Thr Gln755 760 765

ttc gag acg tcg ggt gcc ate aac cga tac tat gtc cag aat ggc gtc 2352

Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr Tyr Val Gln Asn Gly Val770 775 780 '

act ttc cag cag ccc aac gcc gag ctt ggt agt tac tet ggc aac gag 2400

Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly Ser Tyr Ser Gly Asn Glu785 790 795 800

etc aac gat gat tac tgc.aca gct gag gag gea gaa ttc ggc gga tcc 2448

Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu Ala Glu Phe Gly Gly Ser805 810 815.

tet ttc tca gac aag ggc ggc ctg act cag ttc aag aag gct acc tet 24 96

Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln Phe Lys Lys Ala Thr Ser820 825 830

ggc ggc atg gtt ctg gtc atg agt ctg tgg gat gat tac tac gcc aac 254 4

Gly Gly Met Val Leu Val Met Ser Leu Trp Asp Asp Tyr Tyr Ala Asn835 840 845

atg ctg tgg ctg gac tcc acc tac ccg aca aac gag acc tcc tcc aca 2592

Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr Asn Glu Thr Ser Ser Thr850 855 860

ccc ggt gcc gtg cgc gga age tgc tcc acc age tcc ggt gtc cct gct 2640

Pro Gly Ala Val Arg Gly Ser Cys Ser Thr Ser Ser Gly Val Pro Ala865 870 875 ■ 880

cag gtc gaa tet cag tet ccc aac gcc aag gtc acc.ttc tcc aac ate 2688

Gln Val Glu Ser Gln Ser Pro Asn Ala Lys Val Thr Phe Ser Asn Ile885 890 895

aag ttc gga ccc att ggc age acc ggc aac cct age ggc ggc aac cct 2736

Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn Pro Ser Gly Gly Asn Pro900 905 910

ccc ggc gga aac ccg cct ggc acc acc acc acc cgc cgc cca gcc act 2784

Pro Gly Gly Asn Pro Pro Gly Thr Thr Thr Thr Arg Arg Pro Ala Thr915 920 925

acc act gga age tet ccc gga cct acc cag tet cac tac ggc cag tgcThr Thr Gly Ser Ser Pro Gly Pro Thr Gln Ser His Tyr Gly Gln Cys

2832930 935 940

ggc ggt att ggc tac age ggc ccc acg gtc tgc gcc age ggc aca act 2880

Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val Cys Ala Ser Gly Thr Thr945 950 955 960

tgc cag gtc ctg aac cct tac tac tet cag tgc ctg taa 2919

Cys Gln Val Leu Asn Pro Tyr Tyr Ser Gln Cys Leu965 970

<210> 46<211> 972<2i2> PHT

<2I3> Seqüência artificial

<223> Construção Sintética

Pbln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp15 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Tnr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr P145 150

Glu Val His His Val Ser Ser Asn155 160Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys24 5 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys ProLeu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg. Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Ser Ala Cys Thr465 470 475 480

Leu Gln Ser Glu. Thr His Pro Pro Leu Thr Trp Gln Lys Cys Ser Ser485 490 495

Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser Val Val Ile Asp Ala Asn500 505 510

Trp Arg Trp Thr His Ala Thr Asn Ser Ser Thr Asn Cys Tyr Asp Gly515 520 525

Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp Asn Glu Thr Cys Ala Lys530 535 540

Asn Cys Cys Leu Asp Gly Ala Ala'Tyr Ala Ser Thr Tyr. Gly Val Thr545 550 555 560

JThr Ser Gly Asn Ser Leu Ser Ile Gly Phe Val Thr Gln Ser Ala Gln565 570 575

Lys Asn Val Gly Ala Arg Leu Tyr Leu Met Ala Ser Asp Thr Thr Tyr580 585 590

Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe Ser. Phe Asp Val Asp Val595 600 605

Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala Leu Tyr Phe Val Ser Met610 615 620

Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro Thr Asn Thr Ala Gly Ala625 630 635 640

Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln Cys Pro Arg Asp Leu Lys645 650 655Phe Ile Asn Gly Gln Ala Asn Val Glu Gly Trp Glu Pro Ser Ser Asn660 665 670

Asn Ala Asn Thr Gly Ile Gly Gly His Gly Ser Cys Cys Ser Glu Met675 680 685

Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu Ala Leu Thr Pro His Pro690 695 700

Cys Thr Thr Val Gly Gln Glu Ile Cys Glu Gly Asp Gly Cys Gly Gly705 710 715 720

Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr Cys Asp Pro Asp Gly Cys725 730 735

Asp Trp Asn Pro Tyr Arg Lèu Gly Asn Thr Ser Phe Tyr Gly Pro Gly740 745 750

Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys Leu Thr Val Val Thr Gln755 760 765

Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr Tyr Val Gln Asn Gly Val770 775 780

Thr Phe Gln Gln Pró Asn Ala Glu Leu Gly Ser Tyr Ser Gly Asn Glu

785 790 795 800

Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu Ala Glu Phe Gly Gly Ser805 810 815

Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln Phe Lys Lys Ala Thr Ser820 825 830

Gly Gly Met Val Leu Val Met Ser Leu Trp Asp Asp Tyr Tyr Ala Asn835 840 845

Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr Asn Glu Thr Ser Ser Thr850 855 860

Pro Gly Ala Val Arg Gly Ser Cys Ser Thr Ser Ser Gly. Val Pro Ala865 870 875 880

Gln Val Glu. Ser Gln Ser Pro Asn Ala Lys Val Thr Phe Ser Asn Ile885 890 895Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn Pro Ser Gly Gly Asn Pro900 905 910

Pro Gly Gly Asn Pro Pro Gly Thr Thr Thr Thr Arg Arg Pro Ala Thr915 920 925

Thr Thr Gly Ser Ser Pro Gly Pro Thr Gln Ser His Tyr Gly Gln Cys930 935 940

Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val Cys Ala Ser Gly Thr Thr945 950 955 960

Cys Gln Val Leu Asn Pro Tyr Tyr Ser Gln Cys Leu965 970

<210> 47<211> 3057 <2&2> DNA-

<213> Seqüência artificial

<220>

<223> Proteína de fusão

<220>

<221> CDS<222> (1)..(3057)

<400> 47

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg 48

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aat . 96

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 144

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tçt age ttg gtt tca cgg acg tcg tca gca tcc tca 192

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser- Ser50 55 60

tcc gtc ggc tcg tet tca ccc ggc ggc aac tca cca act ggc agt gct 240

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag 288

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tet cct tac ccc age att gcc gca tcc agt tgc gga tcg tgg acc ctc 336

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 4 32

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 4 80

Cys Lys Ser Gly Thr Met Tyr Pro. Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 576

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly.Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caaGly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

1056tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gca gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gca gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu He Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat ggc tcg act tac tcc 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

agt gga tet tet tcg ggg tcg ggg tet age tcc age tcg agt tcg act 1488

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

acc act aag gcc act tcg acg acc ttg aag act acc tcg acc acc age 1536

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

agt gga agç agt tcg aca tcg gcg gcg cag tcg gcc tgc act ct.c caa 1584

Ser Gly Ser Ser Ser Thr Ser Ala Ala Gln Ser Ala Cys Thr Leu Gln515 520 525

tcg gag act cac ccg cct ctg aca tgg cag aaa tgc tcg tet'ggt ggc 1632

Ser Glu Thr His Pro Pro Leu Thr Trp Gln Lys Cys Ser Ser Gly Gly530 535 540

acg tgc act caa cag aca ggc tcc gtg gtc ate gac gcc aac tgg cgc 1680

Thr Cys Thr Gln Gln Thr Gly Ser Val Val Ile Asp Ala Asn Trp Arg545 550 555 560

tgg act cac gct acg aac age age acg aac tgc tac gat ggc aac act 1728

Trp Thr His Ala Thr Asn Ser Ser Thr Asn Cys Tyr Asp Gly Asn Thr

565 570 575

tgg age tcg acc cta tgt cct gac aac gag acc tgc gcg aag aac tgc 1776Trp Ser Ser Thr Leu Cys Pro Asp Asn Glu Thr Cys Ala Lys Asn Cys580 585 590tgt ctg gac ggt gcc gcc tac gcg tcc acg tac gga gtt acc acg age L824

Cys Leu Asp Gly Ala Ala Tyr Ala Ser Thr Tyr Gly Val Thr Thr Ser595 600 605

ggt aac age ctc tcc att ggc ttt gtc acc cag tet gcg cag aag aac 1872

Gly Asn Ser Leu Ser Ile Gly Phe Val Thr Gln Ser Ala Gln Lys Asn610 615 620

gtt ggc gct cgc ctt tac ctt atg gcg age gac acg acc tac cag gaa 1920

Val Gly Ala Arg Leu Tyr Leu Met Ala Ser Asp Thr Thr Tyr Gln Glu625 630 635 640

ttc acc ctg ctt ggc aac gag ttc tet ttc gat gtt gat gtt tcg cag 1968

Phe Thr Leu Leu Gly Asn Glu Phe Ser Phe Asp Val Asp Val Ser Gln645 650 655

ctg ccg tgc ggc ttg aac gga gct ctc tac ttc gtg tcc atg gac gcg 2016

Leu Pro Cys Gly Leu Asn Gly Ala Leu Tyr Phe Val Ser Met Asp Ala660 665 670

t ggt ggc gtg age aag tat ccc acc aac acc gct ggc gcc aag tac 2064

Gly Gly Val Ser Lys Tyr Pro Thr Asn Thr Ala Gly Ala Lys Tyr675 680 685

ggc acg ggg tac tgt gac age cag tgt ccc cgc gat ctg aag ttc ate 2112

Gly Thr Gly Tyr Cys Asp Ser Gln Cys Pro Arg Asp Leu Lys Phe Ile690 695 700

aat ggc cag gcc aac gtt gag ggc tgg gag ccg tca tcc aac aac gcg 2160

Asn Gly Gln Ala Asn Val Glu Gly Trp Glu Pro Ser Ser Asn Asn Ala705 710 715 720

aac acg ggc att gga gga cac gga age tgc tgc tet gag atg gat ate 2208

Asn Thr Gly Ile Gly Gly His Gly Ser Cys Cys Ser Glu Met Asp Ile725 730 735

tgg gag gcc aac tcc ate tcc gag gct ctt acc ccc cac cct tgc acg 2256Trp Glu Ala Asn Ser Ile Ser Glu Ala Leu Thr Pro His Pro Cys Thr740 745 750

ct gtc ggc cag gag ate tgc gag ggt gat ggg tgc ggc gga act tac 2304

ir Val Gly Gln Glu Ile Cys Glu Gly Asp Gly Cys Gly Gly Thr Tyr755 760 765

tcc gat aac aga tat ggc ggc act tgc gat ccc gat ggc tgc gac tgg 2352

Ser Asp Asn Arg Tyr Gly Gly Thr Cys Asp Pro Asp Gly Cys Asp Trp770 775 780

aac cca tac cgc ctg ggc aac acc age ttc tac ggc cct ggc tca age 2400

Asn Pro Tyr Arg Leu Gly Asn Thr Ser Phe Tyr Gly Pro Gly Ser Ser785 790 795 800

ttt acc ctc gat acc acc aag aaa ttg acc gtt gtc acc cag ttc gag 2448

Phe Thr Leu Asp.Thr Thr Lys Lys Leu Thr Val Val Thr Gln Phe Glu805 810 815

acg tcg ggt gcc ate aac cga tac tat gtc cag aat ggc gtc act ttc 2496

Thr Ser C-Iy Ala Ile Asn Arg Tyr Tyr Val Gln Asn Gly Val Thr Phe820 825 830

cag cag ccc aac gcc gag ctt ggt agt tac tet ggc aac gag ctc aac

2544Gln Gln Pro Asn Ala Glu Leu Gly Ser Tyr Ser Gly Asn Glu Leu Asn835 840 845

gat gat tac tgc aca gct gag gag gca gaa ttc ggc gga tcc tct ttc 2592

Asp Asp Tyr Cys Thr Ala Glu Glu Ala Glu Phe Gly Gly Ser Ser Phe850 855 860

tca gac aag ggc gga ctg act cag ttc aag aag gct acc tct ggc ggc 2640

Ser Asp Lys Gly Gly Leu Thr Gln Phe Lys Lys Ala Thr Ser Gly Gly865 870 875 880

atg gtt ctg gtc atg agt ctg tgg gat gat tac tac gcc aac atg ctg 2688

Met Val Leu Val Met Ser Leu Trp Asp Asp Tyr Tyr Ala Asn Met Leu885 890 895

tgg ctg gac tcc acc tac ccg aca aac gag acc tcc tcc aca ccc ggt 2736

Trp Leu Asp Ser Thr Tyr Pro Thr Asn Glu Thr Ser Ser Thr Pro Gly900 905 910

gcc gtg cgc gga age tgc tcc acc age tcc ggt gtc cct gct cag gtc 2784

lia Val Arg Gly Ser Cys Ser Thr Ser Ser Gly Val Pro Ala Gln Val915 920 925

gaa tct cag tct ccc aac gcc aag gtc acc ttc tcc aac ate aag ttc 2832Glu Ser Gln Ser Pro Asn Ala Lys Val Thr Phe Ser Asn Ile Lys Phe930 935 940

gga ccc att ggc age acc ggc aac cct age ggc ggc aac cct ccc ggc 2880

Gly Pro Ile Gly Ser Thr Gly Asn Pro Ser Gly Gly Asn Pro Pro Gly945 950 955 960

gga aac ccg cct ggc acc acc acc acc cgc cgc cca gcc act acc act 2928

Gly Asn Pro Pro Gly Thr Thr Thr Thr Arg Arg Pro Ala Thr Thr Thr965 970 975

gga age tct ccc gga cct acc cag tct cac tac- ggc cag tgc ggc ggt 2976

Gly Ser Ser Pro Gly Pro Thr Gln Ser His Tyr Gly Gln Cys Gly Gly980 985 990

att ggc tac age ggc ccc acg gtc tgc gcc age ggc aca act tgc cag 3024Ile Gly Tyr Ser Gly Pro Thr Val Cys Ala Ser Gly Thr Thr Cys Gln995 1000 1005

gtc ctg aac cct tac tac tct cag tgc ctg taa 3057

Val Leu Asn Pro Tyr Tyr Ser Gln'Cys Leu1010 1015

<210> 48

<211> .. 1018 -

<212> .PRT____

<213> Seqüêiicia artificial

<220> _ __ _____

<223> Construção Sintética

<400> 48

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

ler Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 ' 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

Ser Gly Ser Ser Ser Thr Ser Ala Ala Gln Ser Ala Cys Thr Leu Gln515 520 525

Ser Glu Thr His Pro Pro Leu Thr Trp Gln Lys Cys Ser Ser Gly Gly530 535 540

Thr Cys Thr Gln Gln Thr Gly Ser Val Val Ile Asp Ala Asn Trp Arg545 550 555 560

Trp Thr His Ala Thr Asn Ser Ser Thr Asn Cys Tyr Asp Gly Asn Thr565 570 575

Trp Ser Ser Thr Leu Cys Pro Asp Asn Glu Thr Cys Ala Lys Asn Cys580 585 590

Cys Leu Asp Gly Ala Ala Tyr Ala Ser Thr Tyr Gly Val Thr Thr Ser595 600 605

Gly Asn Ser Leu Ser Ile Gly Phe Val Thr Gln Ser Ala Gln Lys Asn610 615 620

Val Gly Ala Arg Leu Tyr Leu Met Ala Ser Asp Thr Thr Tyr Gln Glu625 630 635 640

Phe Thr Leu Leu Gly Asn Glu Phe Ser Phe Asp Val Asp Val Ser Gln645 650 655

Leu Pro Cys Gly Leu Asn Gly Ala Leu Tyr Phe Val Ser Mét. Asp Ala660 665 670

Asp Gly Gly Val Ser Lys Tyr Pro Thr Asn Thr Ala Gly Ala Lys Tyr675 680 685

Gly Thr Gly Tyr Cys Asp Ser Gln Cys Pro Arg Asp Leu Lys Phe Ile690 695 700

Asn Gly Gln Ala Asn Val Glu Gly Trp Glu Pro Ser Ser Asn Asn Ala705 710 715 720

Asn Thr Gly Ile Gly Gly His Gly Ser Cys Cys Ser Glu Met Asp Ile725 730 735

Trp Glu Ala Asn Ser Ile Ser Glu Ala Leu Thr Pro His Pro Cys Thr740 745 750Thr Val Gly Gln Glu Ile Cys Glu Gly Asp Gly Cys Gly Gly Thr Tyr755 760 765

Ser Asp Asn Arg Tyr Gly Gly Thr Cys Asp Pro Asp Gly Cys Asp Trp770 775 780

Asn Pro Tyr Arg Leu Gly Asn Thr Ser Phe Tyr Gly Pro Gly Ser Ser785 790 795 800

Phe Thr Leu Asp Thr Thr Lys Lys Leu Thr Val Val Thr Gln Phe Glu805 810 815

Thr Ser Gly Ala Ile Asn Arg Tyr Tyr Val Gln Asn Gly Val Thr Phe820 825 830

Gln Gln Pro Asn Ala Glu Leu Gly Ser Tyr Ser Gly Asn Glu Leu Asn835 840 845

Asp Asp Tyr Cys Thr Ala Glu Glu Ala Glu Phe Gly Gly Ser Ser Phe850 855 860

Ser Asp Lys Gly Gly Leu Thr Gln Phe Lys Lys Ala Thr Ser Gly Gly865 870 875 880

Met Val Leu Val Met Ser Leu.Trp Asp Asp Tyr Tyr Ala Asn Met Leu885 890 895

Trp Leu Asp Ser Thr Tyr Pro Thr Asn Glu Thr Ser Ser Thr Pro Gly900 905 910

Ala Val Arg Gly Ser Cys Ser Thr Ser Ser Gly Val Pro Ala Gln Val915 920 925

Glu Ser Gln Ser Pro Asn Ala Lys Val Thr Phe Ser Asn Ile Lys Phe930 935 940

Gly Pro Ile Gly Ser Thr Gly Asn Pro Ser Gly Gly Asn Pro Pro Gly945 950 955 960

Gly Asn Pro Pro Gly Thr Thr Thr Thr Arg Arg Pro Ala Thr Thr Thr965 970 975

Gly Ser Ser Pro Gly Pro Thr Gln Ser His Tyr Gly Gln Cys Gly Gly980 985 990Ile Gly Tyr Ser Gly Pro Thr Val Cys Ala Ser Gly Thr Thr Cys Gln995 1000 1005

Val Leu Asn Pro Tyr Tyr Ser Gln Cys Leu1010 1015

<210> 49<211> 27;69

DNA

Seqüência: artificial

<212><213>

<220>

<223> Proteína de fusão

<220><221><222>

CDS(1)

(2769)

Γ400> 49cag cag aatGln Gln Asn

tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tggCys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp5 10 15

48

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

96

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aacAsp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

144

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tcaGly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

192

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gctSer Val Gly Ser Sèr Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala5 70 75 80

240

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg.cagSer Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

288

tct cct tac ccc age att gcc gca tcc agt tgc gga tcg tgg acc ctcSer Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

336

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tccVal Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

38

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gacGlu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

432

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aacCvs Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn

480145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt, ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 576

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc çtg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg ^ac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gccVal Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

1200ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cg.t ctg act age cca acg ggg gaa cag att gtg aat gaa cag 134 4

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat caa gct tgc tca age 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Ala Cys Ser Ser465 470 475 480

tc tgg ggc caa tgt ggt ggc cag aat tgg tcg ggt ccg act tgc tgt 1488

Val Trp Gly Gln Cys Gly Gly Gln Asn Trp Ser Gly Pro Thr Cys Cys485 490 495

gct tcc gga age aca tgc gtc tac tcc aac gac tat tac tcc cag tgt 1536

Ala Ser Gly Ser Thr Cys Val Tyr Ser Asn Asp Tyr Tyr Ser Gln Cys500 505 510

ctt ccc ggc gct gea age tca age tcg tcc acg cgc gcc gcg tcg acg 1584

Leu Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr515 520 525

act tet cga gta tcc ccc aca aca tcc cgg tcg age tcc gcg acg cct 1632

Thr Ser Arg Val Ser Pro Thr Thr Ser Arg Ser Ser Ser Ala Thr Pro530 535 540

cca cct ggt tet act act acc aga gta cct cca gtc gga tcg gga acc 1680

Pro Pro Gly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser Gly Thr545 550 555 560

gct acg tat tca ggc aac cct ttt gtt ggg gtc act cct tgg gcc aat 1728

Ala Thr Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp Ala Asn565 570 575

gea tat tac gcc tet gaa gtt age age ctc gct att cct age ttg act 177 6

Ala Tyr Tyr Ala Ser Glu Val Ser Ser Leu Ala Ile Pro Ser Leu Thr580 585 590

gga gcc atg gcc act gct gea gea gct gtc gea aag gtt ccc tet ttt 1824

Gly Ala Met Ala Thr Ala Ala Ala Ala Val Ala Lys Val Pro Ser Phe595 600 605

atg tgg cta gat act ctt gac aag acc cct ctc atg gag caa acc ttg 1872

Met Trp Leu Asp Thr Leu Asp Lys Thr Pro Leu Met Glu Gln Thr Leu610 615 620

gcc gac ate cgc acc gcc aac aag aat ggc ggt aac tat gcg gga cag 1920

Ala Asp Ile Arg Thr Ala Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln625 630 635 640ttt gtg gtg tat gac ttg ccg gat cgc gat tgc gct gcc ctt gcc tcg 1968

Phe Val Val Tyr Asp Leu Pro Asp Arg Asp Cys Ala Ala Leu Ala Ser645 650 655

aat ggc gaa tac tct att gcc gat ggt ggc gtc gcc aaa tat aag aac 2016

Asn Gly Glu Tyr Ser Ile Ala Asp Gly Gly Val Ala Lys Tyr Lys Asn660 665 670

tat ate gac acc att cgt caa att gtc gtg gaa tat tcc gat ate cgg 2064

Tyr Ile Asp Thr Ile Arg Gln Ile Val Val Glu Tyr Ser Asp Ile Arg675 680 685

acc ctc ctg gtt att gag cct gac tct ctt gcc aac ctg gtg acc aac 2112

Thr Leu Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val Thr Asn690 695 700

ctc ggt act cca aag tgt gcc aat gct cag tca gcc tac ctt gag tgc 2160

Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala Tyr Leu Glu Cys705 710 715 720

ate aac tac gcc gtc aca cag ctg aac ctt cca aat gtt gcg atg tat 2208

|Ile Asn Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala ,Met.. Tyr725 730 7-35

ttg gac gct ggc cat gea gga tgg ctt ggc tgg ccg gea aac caa gac 225 6Leu Asp Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp740 745 750

ccg gcc gct cag cta' ttt gea aat gtt tac aag aat gea tcg tct ccg 2304

Pro Ala Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro755 760 765

aga gct ctt cgc gga ttg gea acc aat gtc gcc aac tac aac ggg tgg 2352

Arg Ala Leu Arg Gly Leu Ala Thr Asn Vàl Ala Asn Tyr Asn Gly Trp770 775 780

aac att acc age ccc cca tcg tac acg caa ggc aac gct gtc tac aac 2400

Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln Gly Asn Ala Val Tyr Asn785 790 795 800

gag aag ctg tac ate cac gct att gga cgt ctt ctt gcc aat cac ggc 2448

Glu Lys Leu Tyr Ile His Ala Ile Gly Arg Leu Leu Ala Asn His Gly805 810 815

tgg tcc aac gcc ttc ttc ate act gat caa ggt cga tcg gga aag cag 24 96

Trp Ser Asn Ala Phe Phe Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln820 825 830

cct acc gga cag caa cag tgg gga gac tgg tgc aat gtg ate ggc acc 254 4

Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile Gly Thr835 840 845

gga ttt ggt att cgc cca tcc gea aac act ggg gac tcg ttg ctg gat 2592

Gly Phe Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp850 855 860

tcg ttt gtc tgg gtc aag cca ggc ggc gag tgt gac ggc acc age gac 2640

Ser Phe Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp865 870 875 880

age agt gcg cca cga ttt gac tcc cac tgt gcg ctc cca gat gcc ttg 2688Ser Ser Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp Ala Leu885 890 895

caa ccg gcg gct caa gct ggt gct tgg ttc caa gcc tac ttt gtg cag 2736Gln Pro Ala Ala Gln Ala Gly Ala Trp Phe Gln Ala Tyr Phe Val Gln900 905 910

ctt ctc aca aac gca aac cca tcg ttc ctg taa 2769

Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu915 920

<210> 50

<211> 922

<212> PRT,

<213> Sequencia artificial

<220> Construcao SIntetica

<223>

<400> 50

Gln Glri Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp

1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu -Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155' 160Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 · 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala: Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Ala Cys Ser Ser465 470 475 480

|al Trp Gly Gln Cys Gly Gly Gln Asn Trp Ser Gly Pro Thr Cys Cys485 490 495

Ala Ser Gly Ser Thr Cys Val Tyr Ser Asn Asp Tyr Tyr Ser Gln Cys500 505 510

Leu Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr515 520 525

Thr Ser Arg Val Ser Pro Thr Thr Ser Arg Ser Ser Ser Ala Thr Pro530 535 540

Pro ProGly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser Gly Thr545 550 555 560

JAla Thr Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp Ala Asn565 570 575

Ala Tyr Tyr Ala Ser Glu Val Ser Ser Leu Ala Ile Pro Ser Leu Thr580 585 590

Gly Ala Met Ala Thr Ala Ala Ala Ala Val Ala Lys Val Pro Ser Phe595 600 605

Met Trp Leu Asp Thr Leu Asp Lys Thr Pro Leu Met Glu Gln Thr Leu610 615 620

Ala Asp Ile Arg Thr Ala Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln625 630 635 640

Phe Val Val Tyr Asp Leu Pro Asp Arg Asp Cys Ala Ala Leu Ala Ser645 650 655

Asn Gly Glu Tyr Ser Ile Ala Asp Gly Gly Val Ala Lys Tyr Lys Asn660 665 670

Tyr Ile Asp Thr Ile Arg Gln Ile Val Val Glu Tyr Ser Asp Ile Arg675 680 685

Thr Leu Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val Thr Asn690 695 700

Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala Tyr Leu Glu Cys705 710 715 720

Ile Asn Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala Met Tyr725 730 735

Leu Asp Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp740 745 750

Pro Ala Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro755 760 765

Arg Ala Leu.Arg Gly Leu Ala Thr Asn Val Ala Asn Tyr Asn Gly Trp770 775 780

Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln Gly..Asn Ala Val Tyr Asn785 790 795 800

Glu Lys Leu Tyr Ile His Ala Ile Gly Arg Leu Leu Ala Asn His Gly805 810 815

Trp Ser Asn Ala Phe Phe Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln820 825 830

Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile Gly Thr835 840 845

Gly Phe Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp850 855 860

Ser Phe Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp865 870 875 880

Ser Ser Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp Ala Leu885 890 895Gln Pro Ala Ala Gln Ala Gly Ala Trp Phe Gln Ala Tyr Phe Val Gln900 905 910

Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu915 920

<210><211>

51-2907

<211> DNA<213> Seqüência artificial

<220>

<230> 1 Proteína de fusão1 l

<220>

<221> CDS<222> (1)..(2907)

<400> 51

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp15 10 15

48

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

96

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aacAsp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

144

gga aca act tcc tct age.ttg gtt tca cgg acg tcg tca gca tcc tcaGly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

192

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct|Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 · 70 75 80

240

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cagSer Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

288

tct cct tac ccc age att gcc gca tcc agt tgc gga tcg tgg acc ctcSer Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

336

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tccVal Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser'115 120 125

384

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gacGlu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

432

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac

480Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 57 6

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr'Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aág ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 8 64

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

^ys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 105 6

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gca gac acc gac aac tgg gtt gccVal Thr Lys Ile Glu Ile Lys Glv Ala Asp Thr Asp Asn Trp Val Ala 1200385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 12 96:

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat ggc tcg act tac tcc 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

igt gga tet tet tcg ggg tcg ggg tet age tcc age tcg agt tcg act 14 88

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

acc act aag gcc act tcg acg acc ttg aag act acc tcg acc acc age 1536

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

agt gga age agt tcg aca tcg gcg gcg caa gct tgc- tca age gtc tgg 1584

Ser Gly Ser Ser Ser Thr Ser Ala Ala Gln Ala Cys Ser Ser Val Trp515 520 525

ggc caa tgt ggt ggc. cag aat tgg tcg ggt ccg act tgc tgt gct tcc 1632

Gly Gln Cys Gly Gly Gln Asn Trp Ser Gly Pro Thr Cys Cys Ala Ser530 535 540

gga age aca tgc gtc tac tcc aac gac tat tac tcc cag tgt ctt ccc 1680

Gly Ser Thr Cys Val Tyr Ser Asn Asp Tyr Tyr Ser Gln Cys Leu Pro

545 550 555 560

ggc gct gea age tca age tcg tcc acg cgc gcc gcg tcg acg act tet 1728

Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr Thr Ser565 570 575

cga gta tcc ccc aca aca tcc cgg tcg age tcc gcg acg cct cca cct 177 6

Arg Val Ser Pro Thr Thr Ser Arg Ser Ser Ser Ala Thr Pro Pro Pro580 585 590

ggt tet act act acc aga gta cct cca gtc gga tcg gga acc gct acg 1824

Gly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser Gly Thr Ala Thr595 600 605

tat tca ggc aac cct ttt gtt ggg gtc act cct tgg gcc aat gea tat 1872

Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp Ala Asn Ala Tyr610 615 620

tac gcc tet gaa gtt age age etc gct att cct age ttg act gga gccTyr Ala Ser Glu Val Ser Ser Leu Ala Ile Pro Ser Leu Thr Gly Ala625 630 635 640

1920atg gcc act gct gca gca gct gtc gca aag gtt ccc tct ttt atg tgg 1968

Met Ala Thr Ala Ala Ala Ala Val Ala Lys Vai Pro Ser Phe Met Trp645 650 655

cta gat act ctt gac aag acc cct ctc atg gag caa acc ttg gcc gac 2016

Leu Asp Thr Leu Asp Lys Thr Pro Leu Met Glu Gln Thr Leu Ala Asp660 665 670

ate cgc acc gcc aac aag aat ggc ggt aac tat gcg gga cag ttt gtg 2064

Ile Arg Thr Ala Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln Phe Val675 680 685

gtg .tat gac ttg ccg gat cgc gat tgc gct gcc ctt gcc tcg aat ggc 2112

Val Tyr Asp Leu Pro Asp Arg Asp Cys. Ala Ala Leu Ala Ser Asn Gly690 695 700

gaa tac tct att gcc gat ggt ggc gtc gcc aaa tat aag aac tat ateGlu Tyr Ser Ile Ala Asp Gly Gly Val Ala Lys Tyr Lys Asn Tyr Ile705 710 715 720

2160

^ac acc att cgt caa att gtc gtg gaa tat tcc gat ate cgg acc ctc 2208

wAsp Thr Ile Arg Gln Ile Val Val Glu Tyr Ser Asp Ile Arg Thr Leu725 730 735

ctg gtt att gag cct gac tct ctt gcc aac ctg gtg acc aac ctc ggt 2256. Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val Thr Asn Leu Gly740 745 750

act cca aag tgt gcc aat gct cag tca gcc tac ctt gag tgc ate aac 2304

Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala Tyr Leu Glu Cys Ile Asn755 760 765

tac gcc gtc aca cag ctg aac ctt cca aat gtt gcg atg tat ttg gac 2352

Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala Met Tyr Leu Asp770 775 .780

gct ggc cat gca gga tgg ctt ggc tgg ccg gca aac caa gac ccg gcc 2400

Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp Pro Ala785 790. 795 800

^gct cag cta ttt gca aat gtt tac aag aat gca. t.c,g t.ct ccg aga gct 2448

Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro Arg Ala805 810 815

ctt cgc gga ttg gca acc aat gtc gcc aac tac aac ggg tgg aac att 24 96

Leu Arg Gly Leu Ala Thr Asn Val Ala Asn Tyr Asn Gly Trp Asn Ile820 825 830

acc age ccc cca tcg tac acg caa ggc aac gct gtc tac aac gag aag 254 4

Thr Ser Pro Pro Ser Tyr Thr Gln Gly Asn Ala Val Tyr Asn Glu Lys835 840 845

ctg tac ate cac gct att gga cgt ctt ctt gcc aat cac ggc tgg tcc 2592

Leu Tyr Ile His Ala Ile Gly Arg Leu Leu Ala Asn His Gly Trp Ser850 855 860

aac gcc ttc ttc ate act gat caa ggt cga tcg gga aag cag cct accAsn Ala Phe Phe Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln Pro Thr865 870 875 .880

2640gga cag caa cag tgg gga gac tgg tgc aat gtg ate ggc acc gga ttt 2688Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile Gly Thr Gly Phe885 890 895

ggt att cgc cca tcc gea aac act ggg gac tcg ttg ctg gat tcg ttt 2736

Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp Ser Phe900 905 910

gtc tgg gtc aag cca ggc ggc gag tgt gac ggc acc age gac age agt 278 4

Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp Ser Ser'915 920 925

gcg cca cga ttt gac tcc cac tgt gcg ctc cca gat gcc ttg caa ccg 2832

Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp Ala Leu Gln Pro930 935 940

gcg gct caa gct ggt gct tgg ttc caa gcc tac ttt gtg cag ctt ctc 2880

Ala Ala Gln Ala Gly Ala Trp Phe Gln Ala Tyr Phe Val Gln Leu Leu945 950 955 960

aca aac gea aac cca tcg ttc ctg taa 2907

IThr Asn Ala Asn Pro Ser Phe Leu ·965

<210> 52<211> 968<212> PRT

<213> Seqüência artificial

<220>

<223> Construção Sintética

<400> 52

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75' 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln 85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro He. Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

^ftly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln^^ 435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

ser Gly Ser Ser Ser Thr Ser Ala Ala Gln Ala Cys Ser Ser Val Trp515 520 525

Gly Gln Cys Gly Gly Gln Asn Trp Ser Gly Pro Thr Cys Cys Ala Ser530 535 540

Gly Ser Thr Cys Val Tyr Ser Asn Asp Tyr Tyr Ser. Gln Cys Leu Pro545 550 555 560

Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr Thr Ser565 570 575

Arg Val Ser Pro Thr Thr Ser Arg Ser Ser Ser Ala Thr Pro Pro Pro580 585 590Gly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser Gly Thr Ala Thr595 600 605

Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp Ala Asn Ala Tyr610 615 620

Tyr Ala Ser Glu Val Ser Ser Leu Ala Ile Pro Ser Leu Thr Gly Ala625 630 635 640

Met Ala Thr Ala Ala Ala Ala Val Ala Lys Val Pro Ser Phe Met Trp645 650 655

Leu Asp Thr Leu Asp Lys Thr Pro Leu Met Glu Gln Thr Leu Ala Asp660 665 670

Jle Arg Thr Ala Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln Phe Val675 680 685

Val Tyr Asp Leu Pro Asp Arg Asp Cys Ala Ala Leu Ala Ser Asn Gly690 695 700

Glu Tyr Ser Ile Ala Asp Gly Gly Val Ala Lys Tyr Lys Asn Tyr Ile705 710 715 720

Asp Thr Ile Arg Gln Ile Val Val Glu Tyr Ser Asp Ile Arg Thr Leu725 730 735

Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val Thr Asn Leu Gly740 745 750

Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala Tyr Leu Glu Cys Ile Asn755 760 765

Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala Met Tyr Leu Asp770 775 780

Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp Pro Ala785 790 795 800

Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro Arg Ala805 810 815

Leu Arg Gly Leu Ala Thr Asn Val Ala Asn Tyr Asn Gly Trp Asn Ile820 825 830

Thr Ser Pro Pro Ser Tyr Thr Gln Gly Asn Ala Val Tyr Asn Glu Lys835

840

845

Leu Tyr "He His Ala Ile Gly Arg Leu Leu Ala Asn His Gly Trp Ser850 855 860

Asn Ala Phe Phe Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln Pro Thr865 870 875 880

Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile Gly Thr Gly Phe885 890 895

Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp Ser Phe900 905 910

Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp Ser Ser915 920 925

Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp Ala Leu Glh Pro930 935 940

Ala Ala Gln Ala Gly Ala Trp Phe Gln Ala Tyr Phe Val Gln Leu Leu945 950 955 960

Thr Asn Ala Asn Pro Ser Phe Leu965

<210> 53 <211> 2655 <212> DNA Seqüência artificial l<220> <223> Proteína de fusão <220> <221> CDS <222> (1) (2655) <400> 53 cag cag aat tgc gca g ca tta ttt ggc caa tgt gga ggc ata ggg tggGln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15 tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys 20 Cys Val Ala Gly 25 Ala Gln Cys Ser Phe 30 Val Asngac tgg tac tcc cag tgc Ctt gcg tca acc ggc gga aac ccc cca aacAsp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn

48

96

144

35 40 45gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gea tcc tca .» 192Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 24 0

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 - 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag 288

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc age att gcc gea tcc agt tgc gga tcg tgg acc ctc 336

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 38 4

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 432

Glu Ser Cys Ser Gly Cys Gly Thr' Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 480

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 57 6

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 ' 185 ■ 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 62 4

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 7 68

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250. 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 '375 ; - ' -380

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc cca caa.gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

I Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat ccc ggc gct gea age 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Pro Gly Ala Ala Ser465 470 475 480

tca age tcg tcc acg cgc gcc gcg tcg acg act .tct cga gta tcc ccc 1488

Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr Thr Ser Arg Val Ser Pro

485 490 495

aca aca tcc cgg tcg age tcc gcg acg cct cca cct ggt tct act act 1536

Thr Thr Ser Arg Ser Ser Ser Ala Thr Pro Pro Pro Gly Ser Thr Thr500 505 510

acc aga gta cct cca gtc gga tcg gga acc gct acg tat tca ggc aac 1584

Thr Arg Val Pro Pro Val Gly Ser Gly Thr Ala Thr Tyr Ser Gly Asn515 520 525

cct ttt gtt ggg gtc act cct tgg gcc aat gea tat tac gcc tct gaa 1632

Pro Phe Val Gly Val Thr Pro Trp Ala Asn Ala Tyr Tyr Ala Ser Glu530 535 540

gtt age age ctc gct att cct age ttg act gga gcc atg gcc act gct 1680

Val Ser Ser Leu Ala Ile Pro Ser Leu Thr Gly Ala Met Ala Thr Ala545 5.50 555 560

gea gea gct gtc gea aag gtt ccc tet ttt atg tgg cta gat act ctt 1728

Ala Ala Ala Val Ala Lys Val Pro Ser Phe Met Trp Leu Asp Thr Leu.565 570 575

gac aag acc cct ctc atg gag caa acc ttg gcc gac ate cgc acc gcc 1776

Asp Lys Thr Pro Leu Met Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala580 585 590

aac aag aat ggc ggt aac tat gcg gga cag ttt gtg gtg tat gac ttg 1824

Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu595 6Ò0 605

ccg gat cgc gat tgc gct gcc ctt gcc tcg aat ggc gaa tac tet att 1872

Pro Asp Arg Asp Cys Ala Ala Leu Ala Ser Asn Gly Glu Tyr Ser Ile610 615 620

gcc gat ggt ggc gtc gcc aaa tat aag aac tat ate gac acc att cgtAla Asp Gly Gly Val Ala Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg625 630 635 640

1920

caa att gtc gtg gaa tat tcc gat ate cgg acc ctc ctg gtt att gag 1968

Gln Ile Val Val Glu Tyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu645 650 655

cct gac tet ctt gcc aac ctg gtg acc aac ctc ggt act cca aag tgt 2016

Pro Asp Ser Leu Ala Asn Leu Val Thr Asn Leu Gly Thr Pro Lys Cys660 665 670

gcc aat gct cag tca gcc tac ctt gag tgc ate aac tac gcc gtc aca 2064

Ala Asn Ala Gln Ser Ala Tyr Leu Glu Cys Ile Asn Tyr Ala Val Thr675 680 685

cag ctg aac ctt cca aat gtt gcg atg tat ttg gac gct ggc cat gea 2112

Gln Leu Asn Leu Pro Asn Val Ala Met Tyr Leu Asp Ala Gly His Ala690 695 700

gga tgg ctt ggc tgg ccg gea aac caa gac ccg gcc gct cag cta ttt 2160

Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp Pro Ala Ala Gln Leu- Phe705 710 715 720

gea aat gtt tac aag aat gea tcg tet ccg aga gct ctt cgc gga ttg 2208

Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro.Arg Ala Leu Arg Gly Leu725 730 735

gea acc aat gtc gcc aac tac aac ggg tgg aac att acc age ccc cca 225 6

Ala Thr Asn Val Ala Asn Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro740 745 750

tcg tac acg caa ggc aac gct gtc tac aac gag aag ctg tac ate cac 2304

Ser Tyr Thr Gln Gly Asn Ala Val Tyr Asn Glu Lys Leu Tyr Ile His755 760 765

gct att gga cgt ctt ctt gcc aat cac ggc tgg tcc aac gcc ttc ttc 2352

Ala Ile Gly Arg Leu Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe770 775 780ate act gat caa ggt cga tcg gga aag cag cct acc gga cag caa cag 2400

Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln785 790 795 800

tgg gga gac tgg tgc aat gtg ate ggc acc gga ttt ggt att cgc cca 2448

Trp Gly Asp Trp Cys Asn Val Ile Gly Thr Gly Phe Gly Ile Arg Pro805 810 815

tcc gea aac act ggg gac tcg ttg ctg gat tcg ttt gtc tgg gtc aag 2496Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp Ser Phe Val. Trp Val Lys820 825 830

cca ggc ggc gag tgt gac ggc acc age gac age agt gcg cca cga ttt 2544

Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe835 840 845

gac tcc cac tgt gcg ctc cca gat gcc ttg caa ccg gcg gct caa gct 2592

Asp Ser His Cys Ala Leu Pro Asp Ala Leu Gln Pro Ala Ala Gln Ala850 855 860

ggt gct tgg ttc caa gcc tac ttt gtg cag ctt ctc aca aac gea aac 2640

Gly Ala Trp Phe Gln Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn865 870 875 880

cca tcg ttc ctg taa 2655

Pro Ser Phe Leu

<210> 54

<211> 884

<212> PRT

<213 > Seqüência artificial

<223>Construção, Sintética

<400> 54

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr- Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn• 325 330 335Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr.Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Pro Gly Ala Ala Ser465 470 475 480

Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr Thr Ser Arg Val Ser Pro485 490 495

Thr Thr Ser Arg Ser Ser Ser Ala Thr Pro Pro Pro Gly Ser Thr Thr500 505 510

Thr Arg Val Pro Pro Val Gly Ser Gly Thr; Ala Thr Tyr Ser Gly Asn515 520 525

Pro Phe Val Gly Val Thr Pro Trp Ala Asn Ala Tyr Tyr Ala Ser Glu530 535 540

Val Ser Ser Leu Ala Ile Pro Ser Leu Thr Gly Ala Met Ala Thr Ala545 550 555 560

Ala Ala Ala Val Ala Lys Val Pro Ser Phe Met Trp Leu Asp Thr Leu565 570 575Asp Lys Thr Pro Leu Met Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala580 585 590

Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu595 600 605

Pro Asp Arg Asp Cys Ala Ala Leu Ala Ser Asn Gly Glu Tyr Ser Ile610 615 620

Ala Asp Gly Gly Val Ala Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg625 630 635 640

Gln Ile Val Val Glu Tyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu645 650 655

Pro Asp Ser Leu Ala Asn Leu Val Thr Asn Leu Gly Thr Pro Lys Cys660 665 670

Ala Asn Ala Gln Ser Ala Tyr Leu Glu Cys Ile Asn Tyr Ala Val Thr675 680 685

Gln Leu Asn Leu Pro Asn Val Ala Met Tyr Leu Asp Ala Gly His Ala690 695 700

Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp Pro Ala Ala Gln Leu Phe705 710 715 720.

Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro Arg Ala Leu Arg Gly Leu725 730 735

Ala Thr Asn Val Ala-Asn Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro740 745 750

Ser Tyr Thr Gln Gly Asn Ala Val Tyr Asn Glu Lys Leu Tyr Ile His755 760 765

Ala Ile Gly Arg Leu Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe770 775 780

Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln785 790 795 800

Trp Gly Asp Trp Cys Asn Val Ile Gly Thr Gly Phe Gly Ile Arg Pro805 810 815Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp Ser Phe Val Trp Val Lys820 825 830

Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe835 840 845

Asp Ser His Cys Ala Leu Pro Asp Ala Leu Gln Pro Ala Ala Gln Ala850 855 860

Gly Ala Trp Phe Gln Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn865 870 875 880

Pro Ser Phe Leu

<210> 55<211> 2793

<213> 1 Seqüência artificial1

k.2 2r3 > I Proteína de fusão

<220><22Í> CDS<222> (1)

(2793)

<400> 55

cag cag aat tgc ígca gca tta ttt ggc caa tgt gga ggc ata ggg tgg

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp

1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc.gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

96

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aacAsp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro' Asn35 40 45

144

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tcaGly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

192

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gctSer Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

240

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cagSer Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

288

tct cct tac ccc age att gcc gca tcc agt tgc gga tcg tgg acc ctcSer Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

336gtg gat aat gtt tgc tgc cca tca tat'tgt gct aat gat gac aca tcc 384

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 4 32

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gtâ tcc age aac 480

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 57 6

Gly Ala Cys Gly Phe Gly Leu Tyr Gly.Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Alá Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea g.ct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac.ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 8 64

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp. Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300·

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caaGly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

1056tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gca gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gca gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat. gac cca aac tat acg agt age cgc cca caa gaa cgc tat 124 8

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 ' 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

íg.a att cg.t ctg act age cca acg ggg gaa cag att gtg aat gaa cag 134 4

Ly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg .cag ttt age cag aat ggc tcg act tac tcc 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

agt gga tet tet tcg ggg tcg ggg tet age tcc age tcg agt tcg act 1488

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

acc act aag gcc act tcg acg acc ttg aag act acc tcg acc acc age 1536

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

igt gga age agt tcg aca tcg gcg gcg ccc ggc gct gca age tca age 1584

Ser Gly Ser Ser Ser Thr Ser Ala Ala Pro Gly-Ala Ala Ser Ser Ser515 520 525

tcg tcc acg cgc gcc gcg tcg acg act tet cga gta tcc ccc aca aca 1632

Ser Ser Thr Arg Ala Ala Ser Thr Thr Ser Arg Val Ser Pro Thr Thr530 535 540

tcc cgg tcg age tcc gcg acg cct cca cct ggt tet act act acc aga 1680

Ser Arg Ser Ser Ser Ala Thr Pro Pro Pro Gly Ser Thr Thr Thr Arg545 550 555 560

gta cct cca gtc gga' tcg gga acc gct acg tat tca ggc aac cct ttt. 1728

Val Pro Pro Val Gly Ser Gly Thr Ala Thr Tyr Ser Gly Asn Pro Phe565 570 575

gtt ggg gtc act cct tgg gcc aat gca tat tac gcc tet gaa gtt age 1776

Val Gly Val Thr Pro Trp Ala Asn Ala Tyr Tyr Ala Ser Glu Val Ser58 0 585 5 90

age ctc gct att cct age ttg act gga gcc atg gcc act gct gca gca 1824Ser Leu Ala Ile Pro Ser Leu Thr Gly Ala Met Ala Thr Ala Ala Ala595 600 605

gct gtc gca aag gtt ccc tct ttt atg tgg cta gat act ctt gac aag 1872

Ala Val Ala Lys Val Pro Ser Phe Met Trp Leu Asp Thr Leu Asp. Lys610 615 620

acc cct ctc atg gag caa acc ttg gcc gac ate cgc acc gcc aac aag 1920

Thr Pro Leu Met Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala Asn Lys625 630 635 640

aat ggc ggt aac tat gcg gga cag ttt gtg gtg tat gac ttg ccg gat 1968

Asn Gly Gly Asn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu Pro Asp645 650 655

cgc gat tgc gct gcc ctt gcc tcg aat ggc gaa tac tct att gcc gat 2016

Arg Asp Cys Ala Ala Leu Ala Ser Asn Gly Glu Tyr Ser Ile Ala Asp660 665 670

ggt ggc gtc gcc aaa tat aag aac tat ate gac acc att cgt caa att 2064

Gly Gly Val Ala Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg Gln Ile675 68 0 685

gtc gtg gaa tat tcc gat ate cgg acc ctc ctg gtt att gag cct gac 2112

Val Val Glu Tyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu Pro Asp690 695 700

tct ctt gcc aac ctg gtg acc aac ctc ggt act cca aag tgt gcc aat 2160

Ser Leu Ala Asn Leu Val Thr Asn Leu Gly Thr Pro Lys Cys Ala Asn705 710 715 720

gct cag tca gcc tac ctt gag tgc ate aac tac gcc gtc aca cag ctg 2208

Ala Gln Ser Ala Tyr Leu Glu Cys Ile Asn Tyr Ala Val Thr Gln Leu725 730 735

aac ctt cca aat gtt gcg atg tat ttg gac gct ggc cat gca gga tgg 2256

Asn Leu Pro Asn Val Ala Met Tyr Leu Asp- Ala Gly His Ala Gly Trp740 745 750

ctt ggc tgg ccg gca aac caa gac ccg gcc gct cag cta ttt gca aat 2304

Leu Gly Trp Pro Ala Asn Gln Asp Pro Ala Ala Gln Leu Phe Ala Asn755 760 765

gtt tac aag aat gca tcg tct ccg aga gct ctt cgc gga ttg gca acc 2352

Val Tyr Lys Asn Ala Ser Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr770 775 780

aat gtc gcc aac tac aac ggg tgg aac att acc age ccc cca tcg tac 2400

Asn Val Ala Asn Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr785 790 795 800

acg caa ggc aac gct gtc tac aac gag aag ctg tac ate cac gct att 2448

Thr Gln Gly Asn Ala Val Tyr Asn Glu.Lys Leu Tyr Ile His Ala Ile805 810 815

gga cgt ctt ctt gcc aat cac ggc tgg tcc aac gcc ttc ttc ate act 24 96

Gly Arg Leu Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe Ile Thr820 825 830

gat caa ggt cga tcg gga aag cag cct acc gga cag caa cag tgg ggaAsp Gln Gly Arg Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly

2544835 840 845

gac tgg tgc aat gtg ate ggc acc gga ttt ggt att cgc cca tcc gea 2592

Asp Trp Cys Asn Val Ile Gly Thr Gly Phe Gly Ile Arg Pro Ser Ala850 855 860

aac act ggg gac tcg ttg ctg gat tcg ttt gtc tgg gtc aag cca ggc 2640

Asn Thr Gly Asp Ser Leu Leu Asp Ser Phe Val Trp Val Lys Pro Gly865 870 875 880

ggc gag tgt. gac ggc acc age gac age agt gcg cca cga ttt gac tcc 2688

Gly Glu Cys Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser885 890 895

cac tgt gcg ctc cca gat gcc ttg caa ccg gcg gct caa gct ggt gct 2736

His Cys Ala Leu Pro Asp Ala Leu Gln Pro Ala Ala Gln Ala Gly Ala900 905 910

tgg ttc caa gcc tac ttt gtg cag ctt ctc aca aac gea aac cca tcg 2784

Trp Phe Gln Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn Pro Ser915 920 ' 925

ttc ctg taa 2793

Phe Leu930

<210> 56<211>. .-9.3iQ·.<2L2¥>

<213> Seqüência artificial

<2 2-3> Construção Sintética

<400> . 56

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp15 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr GlySer Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Vai. Ala Pro His Ser Gln85 . 90 95Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ster Trp Thr Leu

100

105

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Ά115 120

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro E130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Vál Ser Ser Asn

110

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly 1165 170

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr 180 185

160

Leu Thr Ser Gly175

Iys Gly Ser Val190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr C

195

200

iys Asp Ala Phe205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr 210 215 220

fly Thr Thr Leu

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr225 230 235

Hihr Gln Phe Trp240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser 245 250

Gly Glu Cys255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp260 265

Tjyr Ala Val Gly270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile V275 280

kl Asp Ser Cys

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro GSLy Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Rro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg L325 330

jau Gln Gly Asn335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr A

rg Arg Val Gln340

345

350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

Ser Gly Ser Ser Ser Thr Ser Ala Ala Pro Gly Ala Ala Ser Ser Ser515 520 525

Ser Ser Thr Arg Ala Ala Ser Thr Thr Ser Arg Val Ser Pro Thr Thr530 535 540

Ser Arg Ser Ser Ser Ala Thr Pro Pro Pro Gly Ser Thr Thr Thr Arg545 550 555 560

Val Pro Pro Val Gly Ser Gly Thr Ala Thr Tyr Ser Gly Asn Pro Phe565 570 575

Val Gly Val Thr Pro Trp Ala Asn Ala Tyr Tyr Ala Ser Glu Val Ser580 585 590Ser Leu Ala Ile Pro Ser Leu Thr Gly Ala Met' Ala Thr Ala Ala Ala595 600 605

Ala Val Ala Lys Val Pro Ser Phe Met Trp Leu Asp Thr Leu Asp Lys-610 615 620

Thr Pro Leu Met Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala Asn Lys625 630 635 640

Asn Gly Gly Asn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu Pro Asp645 650 655

Arg Asp Cys Ala Ala Leu Ala Ser Asn Gly Glu Tyr Ser Ile Ala Asp660 665 670

Gly Gly Val Ala Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg Gln Ile675 680 685

Val Val Glu Tyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu Pro Asp690 695 700

Ser Leu Ala Asn Leu Val Thr Asn Leu Gly Thr Pro Lys Cys Ala Asn705 710 715 720

Ala Gln Ser Ala Tyr.Leu Glu Cys Ile Asn Tyr Ala Val Thr Gln Leu725 730 735

Asn Leu Pro Asn Val Ala Met Tyr Leu Asp Ala Gly His Ala Gly Trp740 7.45 750

Leu Gly Trp Pro Ala Asn Gln Asp Pro Ala Ala Gln Leu Phe Ala Asn755 760 765

Val Tyr Lys Asn Ala Ser Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr770 775 780

Asn Val Ala Asn Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr785 790 795 800

Thr Gln Gly Asn Ala Val Tyr Asn Glu Lys Leu Tyr Ile His Ala Ile805 810 815

Gly Arg Leu Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe Ile Thr820 825 830Asp Gln Gly Arg Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly835 840 845

Asp Trp Cys Asn Val Ile Gly Thr Gly Phe Gly Ile Arg Pro Ser Ala850 855 860

Asn Thr Gly Asp Ser Leu Leu Asp Ser Phe Val Trp Val Lys Pro Gly865 870 875 880

Gly Glu Cys Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser885 890 895

His Cys Ala Leu Pro Asp Ala Leu Gln Pro Ala Ala Gln Ala' Gly Ala900 905 910

Trp Phe Gln Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn Pro Ser915 920 925

Phe Leu930

<210> 57<211> 2739<212> DNA<213> Sequencia artificial

<220><223> Proteina de fusao

<220> <221> CDS<222> (1)..(2739)

<400> 57

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg 48Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aat 96Ser Gly Thr Thr Cys Cys Val Ala .Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 144Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tca 192Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag 288

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc age att gcc gea tcc agt tgc gga tcg tgg acc ctc 336

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act' acg ccg ccc tcg gcg gac 432

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 480

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn|45 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 57 6

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Jhr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg . 720

kArg Gly Asn Phe Ala Ala Pro- Asn Gly Asp Tyr Tyr Thr Gln Phe Trp>25 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 864

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 124 8

bu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat cag caa ccg ggt acc 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Gln Pro Gly Thr465 470 475 480

c acc ccc gag gtc cat ccc aag ttg aca acc tac aag.tgt aca aag 1488

rer. Thr Pro Glu. Val His Pro Lys Leu Thr Thr Tyr Lys Cys Thr Lys485 490 495

tcc ggg ggg tgc gtg gcc cag gac acc tcg gtg gtc ctt gac tgg aac 1536

Ser Gly Gly Cys Val Ala Gln Asp Thr Ser Val Val Leu Asp Trp Asn500 505 510

tac cgc tgg atg cac gac gea aac tac aac tcg tgc acc gtc aac ggc 1584

Tyr Arg Trp Met His Asp Ala Asn Tyr Asn Ser Cys Thr Val Asn Gly515 520 525

ggc gtc aac acc acg ctc tgc cct gac gag gcg acc tgt ggc aag aac 1632

Gly Val Asn Thr Thr Leu Cys Pro Asp Glu Ala Thr Cys Gly Lys Asn530 535 540

tgc ttc ate gag ggc .gtc gac tac gcc gcc tcg ggc gtc acg acc tcg 1680

Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala Ser Gly Val Thr Thr Ser545 550 555 560ggc age age ctc acc atg aac cag tac atg ccc age age tet ggc ggc 1728

Gly Ser Ser Leu Thr Met Asn Gln Tyr Met Pro Ser Ser Ser Gly Gly565 570 575

tac age age gtc tet cct cgg ctg tat ctc ctg gac tet gac ggt gag 177 6

Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu Leu Asp Ser Asp Gly Glu580 585 590

tac gtg atg ctg aag ctc aac ggc cag gag ctg age ttc gac gtc gac 1824

Tyr Val Met Leu Lys Leu Asn Gly Gln Glu Leu Ser Phe Asp Val Asp595 600 605

ctc tet gct ctg ccg tgt gga gag aac ggc tcg ctc tac ctg tet cag 1872

Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly Ser Leu Tyr Leu Ser Gln610 615 620

atg gac gag aac ggg ggc gcc aac cag tat aac'acg gcc ggt gcc aac 1920

Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr Asn Thr Ala Gly Ala Asn625 630 635 640

tac ggg age ggc tac tgc gat gct cag tgc ccc gtc cag aca tgg agg 1968

yr Gly Ser Gly Tyr Cys. Asp Ala Gln Cys Pro Val Gln Thr Trp Arg645 650 655

aac ggc acc ctc aac act age cac cag ggc ttc tgc tgc aac gag atg 2016

Asn Gly Thr Leu Asn Thr Ser His Gln Gly Phe Cys Cys Asn Glu Met660 665 670

gat ate ctg gag ggc aac tcg agg gcg aat gcc ttg acc cct cac tet 2064

Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn Ala Leu Thr Pro His Ser675 680 685

tgc acg gcc acg gcc tgc gac tet gcc ggt tgc ggc ttc aac ccc tat 2112

Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly Cys Gly Phe Asn Pro Tyr690 695 700

ggc age ggc tac aaa age tac tac ggc ccc gga gat acc gtt gac acc 2160

Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly Asp Thr Val Asp Thr705 710 .715 720

ccaag acc ttc acc ate ate acc cag ttc aac acg gac aac ggc tcg 2208

jer Lys Thr Phe Thr Ile Ile Thr Gln Phe Asn Thr Asp AsnGly Ser725 730 735

ccc tcg ggc aac ctt gtg age ate acc cgc aag tac cag caa aac ggc 2256

Pro Ser Gly Asn Leu Val Ser Ile Thr Arg Lys Tyr Gln Gln Asn Gly740 745 750

gtc gac ate ccc age gcc cag ccc ggc ggc gac acc ate tcg tcc tgc 2304

Val Asp Ile Pro Ser Ala Gln PrO Gly Gly Asp Thr Ile Ser Ser Cys755 760 765

ccg tcc gcc tca gcc tac ggc ggc ctc gcc acc atg ggc aag gcc ctg 2352

Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala Thr Met Gly Lys Ala Leu770 775 780

age age ggc atg gtg ctc gtg ttc age att tgg aac gac aac age cag 2400

Ser Ser Gly Met Val Leu Val Phe Ser Ile Trp Asn Asp Asn Ser Gln785 790 795 800

tac atg aac tgg ctc gac age ggc aac gcc ggc ccc tgc age age acc

2448Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala Gly Pro Cys Ser Ser Thr805 810 815

gag ggc aac cca tcc aac ate ctg gcc aac. aac ccc aac acg cac gtc 2496

Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn Asn Pro Asn Thr His Val820 825 830

gtc ttc tcc aac ate cgc tgg gga gac att ggg tet act acg aac tcg 2544

Val Phe Ser Asn Ile Arg Trp Gly Asp Ile Gly Ser Thr Thr Asn Ser835 840 845

act gcg ccc ccg ccc ccg cct gcg tcc age acg acg ttt tcg act aca 2592

Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser Thr Thr Phe Ser Thr Thr850 855 860

cgg agg age tcg acg act tcg age age ccg age tgc acg cag act cac 2640

Arg Arg Ser Ser Thr Thr Ser Ser Ser Pro Ser Cys Thr Gln Thr His865 870 875 880

tgg ggg cag tgc ggt ggc att ggg tac age ggg tgc aag acg tgc acg 2688

Trp Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Cys Lys Thr Cys Thr885 890 895

tcg ggc act acg tgc cag tat age aac gac tac tac tcg caa tgc ctt 2736

Ser Gly Thr Thr Cys Gln Tyr Ser Asn Asp Tyr Tyr Ser Gln Cys Leu900 905 910

tag 2739

<210> 58<211> 912<212> PRT

<213> Seqyência· artificial

<220

<223> Construção Sintética

<400> 58

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala'Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys. Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 - 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly .Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn32-5 330 335Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp .Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Iy Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Gln Pro Gly Thr465 470 475 480

Ser Thr Pro Glu Val His Pro Lys Leu Thr Thr Tyr Lys Cys Thr Lys485 490 495

Ser Gly Gly Cys Val Ala Gln Asp Thr Ser Val Val Leu Asp Trp Asn500 505 510

Tyr Arg Trp Met HisAsp Ala Asn Tyr Asn Ser Cys Thr Val Asn Gly515 520 525

Gly Val Asn Thr Thr Leu Cys Pro Asp Glu Ala Thr Cys Gly Lys Asn530 535 540

Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala Ser Gly Val Thr Thr Ser545 550 555 560

Gly Ser Ser Leu Thr Met Asn Gln Tyr Met Pro Ser Ser Ser Gly Gly565 570 575Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu Leu Asp Ser Asp Gly Glu580 585 590

Tyr Val Met Leu Lys Leu Asn Gly Gln Glu Leu Ser Phe Asp Val Asp595 600 605

Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly Ser Leu Tyr Leu Ser Gln610 615 620

Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr Asn Thr Ala Gly Ala Asn625 630 635 640

Tyr Gly Ser Gly Tyr Cys Asp Ala Gln Cys Pro Val Gln Thr Trp Arg645 650 655

PAsn Gly Thr Leu Asn Thr Ser His Gln Gly Phe Cys Cys Asn Glu Met660 665 670

Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn Ala Leu Thr Pro His Ser675 680 685

Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly Cys Gly Phe Asn Pro Tyr690 695 700

Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly Asp Thr Val Asp Thr705 ' 710 715 720

Ser Lys Thr Phe Thr Ile Ile Thr Gln Phe Asn Thr Asp Asn Gly Ser725 730 735

^^ Pro Ser Gly Asn Leu Val Ser Ile Thr Arg Lys Tyr Gln Gln Asn Gly' 740 745 750

Val Asp Ile Pro Ser Ala Gln Pro Gly Gly Asp Thr Ile Ser Ser Cys755 760 765

Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala Thr Met Gly Lys Ala Leu770 775 780

Ser Ser Gly Met Val Leu Val Phe Ser He. Trp Asn Asp Asn Ser Gln785 790 795 800

Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala Gly Pro Cys Ser Ser Thr805 810 815Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn Asn Pro Asn Thr His Val820 825 830

Val Phe Ser Asn Ile Arg Trp Gly835 840

Thr Ala Pro Pro Pro Pro Pro Ala850 855

Arg Arg Ser Ser Thr Thr Ser Ser865 870

Asp Ile Gly Ser Thr Thr Asn Ser845

Ser Ser Thr Thr Phe Ser Thr Thr8 60

Ser Pro Ser Cys Thr Gln Thr His875 880

Trp Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Cys Lys Thr Cys Thr885 890 895

Ser Gly Thr Thr Cys Gln Tyr Ser Asn Asp Tyr Tyr Ser Gln Cys Leu900 905 910

<210> 59<211> 2877

< fetlglfclfilISMái

<213> Seqüência artificial<223> Proteína de fusão

<220>

<221> CDS

<222> (1)(2877)

<4 00> 59

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg 4 8

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp 15 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aat 96

Ser Gly Thr.Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc cag tgcAsp Trp Tyr Ser Gln Cys35

gga aca act tcc tct ageGly Thr Thr Ser Ser Ser50

tcc gtc ggc tcg tct tcaSer Val Gly Ser Ser Ser65 70

ctt gcg tca acc ggc ggaLeu Ala Ser Thr Gly Gly40

ttg gtt tca cgg acg tcgLeu Val Ser Arg Thr Ser55 60

ccc ggc ggc aac tca ccaPro Gly Gly Asn Ser Pro75

aac ccc cca aac 144

Asn Pro Pro Asn45

tca gca tcc tca 192

Ser Ala Ser Ser

act ggc agt gct 240

Thr Gly Ser Ala80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cagSer Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

288tct cct tac ccc age att gcc gea tcc agt tgc gga tcg tgg acc ctc 336

Ser Pro Tyr Pro Ser Ile Ala Ala Ser .Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 432

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 480

Cys Lys Ser Gly Thr Met^Tyr Pro Glu Val His His Val Ser Ser Asn 145 15θ" - 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

gg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 576

Iy Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 8 64

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser.Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aatIle His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

1008gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccg aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152Pro Tyr Tyr Phe Ala. Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gcc 1200Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age .cgc cca caa gaa cgc tat 124 8Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

c agt tgg gta ate. cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296Iy Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 134 4Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat ggc tcg act tac tcc 1440Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr. Tyr Ser465 470 475 480

agt gga tet tet tcg ggg tcg ggg tet age tcc age tcg agt tcg actSer Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

agt gga age agt tcg aca tcg gcg gcg cag caa ccg ggt acc age acc 1584Ser Gly Ser Ser Ser Thr Ser. Ala Ala Gln Gln Pro Gly Thr Ser Thr515 520 525

ccc gag gtc cat ccc aag ttg aca acc tac aag tgt aca aag tcc ggg 1632Pro Glu Val His. Pro Lys Leu Thr Thr Tyr Lys Cys Thr Lys Ser Gly530 535 540

ggg tgc gtg gcc cag gac acc tcg gtg gtc. ctt gac tgg aac tac cgc 1680

Gly Cys Val Ala Gln Asp Thr Ser Val Val Leu Asp Trp Asn Tyr Arg545 550 555 560

tgg atg cac gac gea aac tac aac tcg tgc acc gtc aac ggc ggc gtc 1728Trp Met His Asp Ala Asn Tyr Asn Ser Cys Thr Val Asn Gly Gly Val565 570 575

aac acc acg ctc tgc cct gac gag gcg acc tgt ggc aag aac tgc ttc 177 6Asn Thr Thr Leu Cys Pro Asp Glu Ala Thr Cys Gly Lys Asn Cys Phe580 585 590

ate gag ggc gtc gac tac gcc gcc tcg ggc gtc acg acc tcg ggc age 1824

Ile Glu Gly Val Asp Tyr Ala Ala Ser Gly Val Thr Thr Ser Gly Ser595 600 605

age ctc acc atg aac cag tac atg ccc age age tet ggc ggc tac age 1872

Ser Leu Thr Met Asn Gln Tyr Met Pro Ser Ser Ser Gly Gly Tyr Ser610 615 620

age gtc tet cct cgg ctg tat ctc ctg gac tet gac ggt gag tac gtg 1920

Ser Val Ser Pro Arg Leu Tyr Leu Leu Asp Ser Asp Gly Glu Tyr Val625 630 635 640

atg ctg aag ctc aac ggc cag gag ctg age ttc gac gtc gac ctc tet 1968

Met Leu Lys Leu Asn Gly Gln Glu Leu Ser Phe Asp Val Asp Leu Ser645 .650 655

kgct ctg ccg tgt gga gag aac ggc tcg ctc tac ctg tet cag atg gac 2016

'Ala Leu Pro Cys Gly Glu Asn Gly Ser Leu Tyr Leu Ser Gln Met Asp660 665 670

gag aac ggg ggc gcc aac cag tat aac acg gcc ggt gcc aac tac ggg 2064

Glu Asn Gly. Gly Ala Asn Gln Tyr Asn Thr Ala Gly Ala Asn Tyr Gly675 680 685

âgc ggc tac.tgc gat gct cag tgc ccc gtc cag aca tgg agg. aac ggc 2112

Ser Gly Tyr Cys Asp Ala Gln Cys Pro Val Gln Thr Trp Arg Asn Gly690 695 700

acc ctc aac act age cac cag ggc ttc tgc tgc aac gag atg gat ate 2160

Thr Leu Asn Thr Ser His Gln Gly Phe Cys Cys Asn Glu Met Asp Ile705 '710 ■ 715 720

ctg gag ggc aac tcg agg gcg aat gcc ttg acc cct cac tet tgc acg 2208

Leu Glu Gly Asn Ser Arg Ala Asn Ala Leu Thr Pro His Ser Cys Thr725 730 735

gcc acg gcc tgc gac tet gcc ggt tgc ggc ttc aac ccc tat ggc age 2256

Ala Thr Ala Cys Asp Ser Ala Gly Cys Gly Phe Asn Pro Tyr Gly Ser740 745 750

ggc tac aaa age tac tac ggc ccc gga gat acc gtt gac acc tcc aag 2304

Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly Asp Thr Val Asp Thr Ser Lys755 760 765

acc ttc acc ate ate acc cag ttc aac acg gac aac ggc tcg ccc tcg 2352

Thr Phe Thr Ile Ile Thr Gln Phe Asn Thr Asp Asn Gly Ser Pro Ser770 775 780

ggc aac ctt gtg age ate acc cgc aag tac cag caa aac ggc gtc gac 2400

Gly Asn Leu Val Ser Ile Thr Arg Lys Tyr Gln Gln Asn Gly Val Asp785 790 795 800

ate ccc age gcc cag ccc ggc ggc gac acc ate tcg tcc tgc ccg tcc 2448

Ile Pro Ser Ala Gln Pro Gly Gly Asp Thr Ile Ser Ser Cys Pro Ser805 - 810 815

gcc tca gcc tac ggc ggc ctc gcc acc atg ggc aag gcc ctg age ageAla Ser Ala Tyr Gly Gly Leu Ala Thr Met Gly Lys Ala Leu Ser Ser

24 96820 825 830

ggc atg gtg ctc gtg ttc age att tgg aac gac aac age cag tac atg 2544

Gly Met Val Leu Val Phe Ser Ile Trp Asn Asp Asn Ser Gln Tyr Met835 840 845

aac tgg ctc gac age ggc aac gcc ggc ccc tgc age age a.cc gag ggc 2592

Asn Trp Leu Asp Ser Gly Asn Ala Gly Pro Cys Ser Ser Thr Glu Gly850 855 860

aac cca tcc aac ate ctg gcc aac aac ccc aac acg cac gtc gtc ttc 2640

Asn Pro Ser Asn Ile Leu Ala Asn Asn Pro Asn Thr His Val Val Phe865 870 875 880

tcc aac ate cgc tgg gga gac att ggg tet act acg aac tcg act gcg 2688

Ser Asn Ile Arg Trp Gly Asp Ile Gly Ser Thr Thr Asn Ser Thr Ala885 890 895

ccc ccg ccc ccg cct gcg tcc age acg acg ttt tcg act aca cgg agg 2736

kPro Pro Pro Pro Pro Ala Ser Ser· Thr Thr Phe Ser Thr Thr Arg Arg900 '905 910

age tcg acg act tcg age age ccg age tgc acg cag act cac tgg ggg 2784

Ser Ser Thr Thr Ser Ser Ser Pro Ser Cys Thr Gln Thr His Trp Gly915 920 925

cag tgc ggt ggc att ggg tac age ggg tgc aag acg tgc acg tcg ggc 2832

Gln Cys Gly Gly Ile Gly Tyr Ser Gly Cys Lys Thr Cys Thr Ser Gly930 935 940

act acg tgc cag tat age aac gac tac tac tcg caa tgc ctt tag 2877

Thr Thr Cys Gln Tyr Ser Asn Asp Tyr Tyr Ser Gln Cys Leu945 950 955

<210> 60

<211> 958

<212> PRT

<213> Sequência.artificial

<220>

<223> Cohstrução Sintética

<400> 60

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp

1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

FCys Lys Ser Gly Thr.Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

^^ Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

ÍVal Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

iTyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

Ser Gly Ser Ser Ser Thr Ser Ala Ala Gln Gln Pro Gly. Thr Ser Thr515 520 525

Pro Glu Val His Pro Lys Leu Thr Thr Tyr Lys Cys Thr Lys Ser Gly530 535 540

Gly Cys Val Ala Gln Asp Thr Ser Val Val Leu Asp Trp Asn Tyr Arg545 550 555 560Trp Met His Asp Ala Asn Tyr Asn Ser Cys Thr Val Asn Gly Gly Val565 570 575

Asn Thr Thr Leu Cys Pro Asp Glu Ala Thr Cys Gly Lys Asn Cys Phe580 585 590

Ile Glu Gly Val Asp Tyr Ala Ala Ser Gly Val Thr Thr Ser Gly Ser595 600 605

Ser Leu Thr Met Asn Gln Tyr Met Pro Ser Ser Ser Gly Gly Tyr Ser610 615 620

Ser Val Ser Pro Arg Leu Tyr Leu Leu Asp Ser Asp Gly Glu Tyr Val625 630 635 640

Met Leu Lys Leu Asn Gly Gln Glu Leu Ser Phe Asp Val Asp Leu Ser645 650 655

Ala Leu Pro Cys Gly Glu Asn Gly Ser Leu Tyr Leu Ser Gln Met Asp660 665 670

Glu Asn Gly Gly Ala Asn Gln Tyr Asn Thr Ala Gly Ala Asn Tyr Gly675 680 685

Ser Gly Tyr Cys Asp Ala Gln Cys Pro Val Gln Thr Trp Arg Asn Gly690 695 700

Thr Leu Asn Thr Ser His Gln Gly Phe Cys Cys Asn Glu Met Asp Ile705 710 715 720

Leu Glu Gly.Asn Ser Arg Ala Asn Ala Leu Thr Pro His Ser Cys Thr725 730 735

Ala Thr Ala Cys Asp Ser Ala Gly Cys Gly Phe Asn Pro Tyr Gly Ser740 745 750

Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly Asp Thr Val Asp Thr Ser Lys755 760 765

Thr Phe Thr Ile Ile Thr Gln Phe Asn Thr Asp Asn Gly Ser Pro Ser770 775 780

Gly Asn Leu Val Ser Ile Thr Arg Lys Tyr Gln Gln Asn Gly Val Asp785 790 795 800Ile Pro Ser Ala Gln Pro Gly Gly Asp Thr Ile-Ser Ser Cys Pro Ser805 810 815

Ala Ser Ala Tyr Gly Gly Leu Ala Thr Met Gly Lys Ala Leu Ser Ser820 825 830

Gly Met Val Leu Val Phe Ser Ile Trp Asn Asp Asn Ser Gln Tyr Met835 840 845

Asn Trp Leu Asp Ser Gly Asn Ala Gly Pro Cys Ser Ser Thr Glu Gly850 855 860

Asn Pro Ser Asn Ile Leu Ala Asn Asn Pro Asn Thr His Val Val Phe865 870 875 880

t

er Asn Ile Arg Trp Gly Asp Ile Gly Ser Thr Thr Asn Ser Thr Ala885 890 895

Pro Pro Pro Pro Pro Ala Ser Ser Thr Thr Phe Ser Thr Thr Arg Arg900 905 910

Ser Ser Thr Thr Ser Ser Ser Pro Ser Cys Thr Gln Thr His Trp Gly915 920 925

Gln Cys Gly Gly Ile Gly Tyr Ser Gly Cys Lys Thr Cys Thr Ser Gly930 935 940

Thr Thr Cys Gln Tyr Ser Asn Asp Tyr Tyr Ser Gln Cys Leu945 950 955

<210> 61<211> 2625<212> λ DNA

<213> ' Seqüência artificial . . ; . ......' J

<220 >' .■' -i-V-'·' ·■-■- ^s"'

<223> Proteína de fusão |

<220>

<221> CDS

<222> (1).-(2625).

<4 00> 61

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg

Gln Gln Asn Cys Ala. Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aatSer Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

gac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 144

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gea tcc tca 192

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag 288

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

^ct cct tac ccc age att gcc gea tcc agt tgc gga tcg tgg acc ctc 336

ir Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 4 32

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc ca.t cac gta tcc age aac 4 80

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly

165 170 175

gjgg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 576

ly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

aca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe .195 200 ' 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 7 68

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255 .

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 ' 265 270gaa gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 8 64

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser. Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc aat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga ggg 1104

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

cct tac tat ttt gct ctc acg gea gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gea gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac ccã aac tat acg agt age cgc cca caa gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 1296

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 1344

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat cag caa ccg ggt acc 1440

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Gln Pro Gly Thr465 470 475 480

age acc ccc gag gtc cat ccc aagttg aca acc tac aag tgt aca aag 1488

Ser Thr Pro Glu Val His Pro Lys Leu Thr Thr Tyr Lys Cys Thr Lys485 490 495

tcc ggg ggg tgc gtg gcc cag gac acc tcg gtg gtc ctt gac tgg aac 1536

Ser Gly Gly Cvs Val Ala Gln Asp Thr Ser Val Val Leu Asp Trp Asn500 505 510tac cgc tgg atg cac gac gca aac tac aac tcg tgc acc gtc aac ggc 1584

Tyr Arg Trp Met His Asp Ala Asn Tyr Asn Ser Cys Thr Val Asn Gly515 520 525

ggc gtc aac acc acg ctc tgc cct gac gag gcg acc tgt ggc aag aac 1632

Gly Val Asn Thr Thr Leu Cys Pro Asp Glu Ala Thr Cys Gly Lys Asn530 535 540

tgc ttc ate gag ggc gtc gac tac gcc gcc tcg ggc gtc acg acc tcg 1680

Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala Ser Gly Val Thr Thr Ser545 550 555 560

ggc age age ctc acc atg aac cag tac atg ccc age age tet ggc ggc 1728

Gly Ser Ser Leu Thr Met Asn Gln Tyr Met Pro Ser Ser Ser Gly Gly565 570 575

tac age age gtc tet cct cgg ctg tat ctc ctg gac tet gac ggt gag 177 6

Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu Leu Asp Ser Asp Gly Glu580 585 590

cgtg atg ctg aag ctc aac ggc çag. gag ctg age ttc gac gtc gac 1824

yr Val Met Leu Lys Leu Asn Gly Gln Glu.Leu Ser Phe Asp Val Asp595 600 605

ctc tet gct ctg ccg tgt gga gag aac ggc tcg ctc tac ctg tet cag 1872

Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly Ser Leu Tyr Leu Ser Gln610 615 620

atg gac gag aac ggg ggc gcc aac cag tat aac acg gcc ggt gcc aac 1920

Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr Asn Thr Ala Gly Ala Asn625 630 635 640

tac ggg age ggc tac tgc gat gct cag tgc ccc gtc cag aca tgg agg 1968

Tyr Gly Ser Gly Tyr Cys Asp Ala Gln Cys Pro Val Gln Thr Trp Arg645 650 655

aac ggc acc ctc aac act age cac cag ggc ttc tgc tgc aac gag atg 2016

Asn Gly Thr Leu Asn Thr Ser His Gln Gly Phe Cys Cys Asn Glu Met660 665 670

Jrat ate ctg gag ggc aac tcg agg gcg aat gcc ttg acc cct cac tet 2064

Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn Ala Leu Thr Pro His Ser675 680 685

tgc acg gcc acg gcc tgc gac tet gcc ggt tgc ggc ttc aac ccc tat 2112

Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly Cys Gly Phe Asn Pro. Tyr690 695 700

ggc age ggc tac aaa age tac tac ggc ccc gga gat acc gtt gac acc 2160

Gly Ser Gly Tyr Lys Ser. Tyr Tyr Gly Pro Gly Asp Thr Val Asp Thr705 710 715 720

tcc aag acc ttc acc ate ate acc cag ttc aac acg gac aac ggc tcg 2208

Ser Lys Thr Phe Thr Ile Ile Thr Gln Phe Asn Thr Asp Asn Gly Ser725 730 735

ccc tcg ggc aac ctt gtg age ate acc cgc aag tac cag caa aac ggc 2256

Pro Ser Gly Asn Leu Val Ser Ile Thr Arg Lys Tyr Gln Gln Asn Gly740 745 750

gtc gac ate ccc age gcc cag ccc ggc ggc gac acc ate tcg tcc tgc

2304Val Asp Ile Pro Ser Ala Gln Pro Gly Gly Asp Thr Ile Ser Ser Cys755 760 765

ccg tcc gcc tca gcc tac ggc ggc ctc gcc acc atg ggc aag gcc ctg 2352

Pro Ser Ala Ser AIa Tyr Gly Gly Leu Ala Thr Met Gly Lys Ala Leu770 775 780

age age ggc atg gtg ctc gtg ttc age att tgg aac gac aac age cag 2400

Ser Ser Gly Met Val Leu Val Phe Ser Ile Trp Asn Asp Asn Ser Gln785 7 90 795 800

tac atg aac tgg ctc gac age ggc aac gcc ggc ccc tgc age age acc 2448

Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala Gly Pro Cys Ser Ser Thr805 810 815

gag ggc aac cca tcc aac ate ctg gcc aac aac ccc aac acg.cac gtc 2496

Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn Asn Pro Asn Thr His Val820 825 830

pc ttc tcc aac ate cgc tgg gga gac att ggg tet act acg aac tcg 2544

Va 1 Phe Ser Asn Ile Arg Trp Gly Asp Ile Gly Ser Thr Thr Asn Ser835 840 845

act gcg ccc ccg ccc ccg cct gcg tcc age acg acg ttt tcg act aca 2592

Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser Thr Thr Phe Ser Thr Thr850 855 860

cgg agg age tcg acg act tcg age age ccg age 2625

Arg Arg Ser Ser Thr Thr Ser Ser Ser Pro Ser865 870 875

<210> 62

<211> 875

<212> PRT

<213> Seqüência artificial

<220>

<223> Construção Sintética

<400> 62

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 . 150 155 160

Lu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170· 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

>er Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

5u Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gln Gln Pro Gly Thr465 470 475 480

ler Thr Pro Glu Val His Pro Lys Leu Thr Thr Tyr Lys Cys Thr Lys485 490 495

Ser Gly Gly Cys Val Ala Gln Asp Thr Ser Val Val Leu Asp Trp Asn500 505 510

Tyr Arg Trp Met His Asp Ala Asn Tyr Asn Ser Cys Thr Val Asn Gly.515 520 525

Gly Val Asn Thr Thr Leu Cys Pro Asp Glu Ala Thr Cys Gly Lys Asn530 535 540

Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala Ser Gly Val Thr Thr Ser545 550 555 560

Gly Ser Ser Leu Thr Met Asn Gln Tyr Met Pro Ser Ser Ser Gly GlyTyr Ser Ser Val Ser Pro Arg Leu Tyr Leu Leu Asp Ser Asp Gly Glu580 585 590

Tyr Val Met Leu Lys Leu Asn Gly Gln Glu Leu Ser Phe Asp Val Asp595 600 605

Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly Ser Leu Tyr Leu Ser Gln610 615 620

Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr Asn Thr Ala Gly Ala Asn625 630 635 640

Gly Ser Gly Tyr Cys Asp Ala Gln Cys Pro Val Gln Thr Trp Arg645 650 655

Asn Gly Thr Leu Asn Thr Ser His Gln Gly Phe Cys Cys Asn Glu Met660 665 670

Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn Ala Leu Thr Pro His Ser675 680 685

Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly Cys Gly Phe Asn Pro Tyr690 695 700

Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly Asp Thr Val Asp Thr705 710 715 720

Ser LysThr Phe Thr Ile Ile Thr Gln Phe Asn Thr Asp Asn Gly Ser725 730 735

Pro Ser Gly Asn Leu Val Ser Ile Thr Arg Lys Tyr Gln Gln Asn Gly740 745 750

Val Asp Ile Pro Ser Ala Gln Pro Gly Gly Asp Thr Ile Ser Ser Cys755 760 765

Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala Thr Met Gly Lys Ala Leu770 775 780

Ser Ser Gly Met Val Leu Val Phe Ser Ile Trp Asn Asp Asn Ser Gln785 790 795 800

Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala Gly Pro Cys Ser Ser Thr805 810 815Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn Asn Pro Asn Thr His Val820 825 830

Val Phe Ser Asn Ile Arg Trp Gly Asp Ile Gly Ser Thr Thr Asn Ser835 840 845

Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser Thr Thr Phe Ser Thr Thr850 855 860

Arg Arg Ser Ser Thr Thr Ser Ser Ser Pro Ser865 870 875

<210> 63<211> 2763;20S2>· ,--DNA ■,..·

-2I3> Seqüência artificial

<>2 2 3 > Proteína de fusão

<220>

<221> CDS

<222> (1)..(2763)

<4 00> 63

cag cag aat tgc gca gca tta ttt ggc caa tgt gga ggc ata ggg tgg 48

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp1 5 10 15

tcc ggc acc aca tgt tgc gtt gct ggc gcc cag tgc agt ttt gtc aat 96

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

|[ac tgg tac tcc cag tgc ctt gcg tca acc ggc gga aac ccc cca aac 144

isp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 4 5

gga aca act tcc tct age ttg gtt tca cgg acg tcg tca gca tcc tca 192

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 55 60

tcc gtc ggc tcg tct tca ccc ggc ggc aac tca cca act ggc agt gct 240

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

tcc acc tac aca acc aca gat aca gct acc gtg gct cct cat tcg cag- 288

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

tct cct tac ccc age att gcc gca tcc agt tgc gga tcg tgg acc ctc 336

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

gtg gat aat gtt tgc tgc cca tca tat tgt gct aat gat gac aca tcc 384Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 120 125

gag tca tgc tca ggc tgc ggt acc tgc act acg ccg ccc tcg gcg gac 4 32

Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

tgc aaa tcc gga acc atg tat cca gag gtc cat cac gta tcc age aac 480

Cys Lys Ser Gly. Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 . 155 160

gag age tgg cac tac agt aga tca acc cac ttt ggc cta acg age ggc 528

Glu Ser Trp His Tyr Ser Arg. Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

ggg gcc tgt ggc ttt ggc ctg tac ggt ctc tgc aca aag ggc agt gtt 576

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

^ca gcc age tgg acg gat ccc atg ctt ggc gcg acg tgt gac gct ttt 624

fhr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

tgt aca gcg tat ccc ctg ctt tgc aaa gac cct acc ggc act acc ctt 672

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

cgt ggc aac ttc gea gct cca aac ggc gat tac tac acc caa ttc tgg 720

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

tcc tcg ttg cca gga gcc ctc gat aac tac ctg tcc tgc ggc gag tgc 768

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

att gag ctg ata caa aca aag ccc gat ggg acc gat tat gct gtc gga 816

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

ia a gcc ggc tac acg gat cca att act ctc gag att gtg gac age tgc 8 64

Lu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

ccg tgc age gcg aac tcc aag tgg tgc tgt ggt ccg ggc gcc gat cat . 912

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

tgc gga gag ate gac ttc aaa tac ggc tgt cct ctt cct gct gac age 960

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

att cat ctc gac ctg tca gac att gcc atg ggc cgt ttg cag ggc áat 1008

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

gga tca cta acc aat ggc gtc ate ccg act cga tat aga aga gtc caa 1056

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

tgc ccc aaa gtt ggg aac gcc tac att tgg ctt cga aat ggc gga gggCys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly

1104355 360 365

cct tac tat ttt gct ctc acg gca gtc aac acc aac gga ccg ggc tca 1152

Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

gtc acc aaa ate gag ate aag ggc gca gac acc gac aac tgg gtt gcc 1200

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

ttg gtc cat gac cca aac tat acg agt age cgc cca caa gaa cgc tat 1248

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

ggc agt tgg gta ate cca cag gga tca ggg ccc ttt aac ttg cct gtt 12 96

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

gga att cgt ctg act age cca acg ggg gaa cag att gtg aat gaa cag 134 4

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

gcc ate aag aca ttc act cct ccg gcc aca ggt gac ccc aat ttt tac 1392

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

tac att gac att ggt gtg cag ttt age cag aat ggc tcg act tac tcc 1440

Tyr Ile Asp He Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

agt gga tet tet tcg ggg tcg ggg tet age tcc age tcg agt tcg act 1488

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

acc act aag gcc act tcg acg acc ttg aag act,acc tcg acc acc age 1536

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

agt gga age agt tcg aca tcg gcg gcg cag caa ccg ggt acc age acc 1584

Ser Gly Ser Ser Ser Thr Ser Ala Ala Gln Gln Pro Gly Thr Ser Thr515 520 525

ccc gag gtc cat ccc,aag ttg aca acc tac aag tgt aca aag tcc ggg 1632

Pro Glu Val His Pro Lys Leu Thr Thr Tyr Lys, Cys Thr Lys Ser Gly530 535 540

ggg tgc gtg gcc cag gac acc tcg gtg gtc ctt gac tgg aac tac cgc 1680

Gly Cys Val Ala Gln Asp Thr Ser Val Val Leu Asp Trp Asn Tyr Arg ·545 · 550 555 560

tgg atg cac gac gca aac tac aac tcg tgc acc gtc aac ggc ggc gtc 1728

Trp Met His Asp Ala Asn Tyr Asn Ser Cys Thr Val Asn Gly Gly Val565 570 575

aac acc acg ctc tgc cct gac gag gcg acc tgt ggc aag aac tgc ttc 1776

Asn Thr Thr Leu Cys Pro Asp Glu Ala Thr Cys Gly Lys Asn Cys Phe580 585 590

ate gag ggc gtc gac tac gcc gcc tcg ggc gtc acg acc tcg ggc ageIle Glu Gly Val Asp Tyr Ala Ala Ser Gly Val Thr Thr Ser Gly Ser595 600 605

1824age ctc acc atg aac cag tac atg ccc age age tet ggc ggc tac age 1872

Ser Leu Thr Met Asn Gln Tyr Met Pro Ser Ser Ser Gly Gly Tyr Ser610 615 620

age gtc tet cet cgg ctg tat ete ctg gac tet gac ggt gag tac gtg 1920

Ser Val Ser Pro Arg Leu Tyr Leu Leu Asp Ser Asp Gly Glu Tyr Val625 630 635 640

atg ctg aag ctc aac ggc cag gag ctg age ttc gac gtc gac ctc tet 1968

Met Leu Lys Leu Asn Gly Gln Glu Leu Ser Phe Asp Val Asp Leu Ser645 650 655

gct ctg ccg tgt· gga gag aac ggc tcg ctc tac ctg tet cag atg gac 2016

Ala Leu Pro Cys Gly Glu Asn Gly Ser Leu Tyr Leu Ser Gln Met Asp660 665 670

gag aac ggg ggc gcc aac cag tat aac acg gcc ggt gcc aac tac ggg 2064

Glu Asn Gly Gly Ala Asn Gln Tyr Asn Thr Ala Gly Ala Asn Tyr Gly675 680 685

age ggc tac tgc gat gct cag tgc ccc gtc cag aca tgg agg aac ggc 2112

Ser Gly Tyr Cys Asp Ala Gln Cys Pro Val Gln Thr Trp Arg Asn Gly.690 695 700

acc ctc aac act age cac cag ggc ttc tgc tgc aac gag atg gat ate 2160

Thr Leu Asn Thr Ser His Gln Gly Phe Cys Cys Asn Glu Met Asp Ile705 710 715 720

ctg gag ggc aac tcg agg gcg aat gcc ttg acc cct cac tet tgc acg 2208

Leu Glu Gly Asn Ser Arg Ala Asn Ala Leu Thr Pro His Ser Cys Thr725 730 735

gcc acg gcc tgc gac tet gcc ggt tgc ggc ttc aac ccc tat ggc age 2256

Ala Thr Ala Cys Asp Ser Ala Gly Cys Gly Phe' Asn Pro Tyr Gly Ser740 745 750

ggc tac aaa age tac tac ggc ccc gga gat acc gtt gac acc tcc aag 2304

Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly Asp Thr Val Asp Thr Ser Lys755 760 765

acc ttc acc ate ate acc cag ttc aac acg gac aac ggc tcg ccc tcg 2352

Thr Phe Thr Ile Ile Thr Gln Phe Asn Thr Asp Asn Gly Ser Pro Ser770 775 780

ggc aac ctt gtg age ate acc cgc aag tac cag caa aac ggc gtc gac 2400

Gly Asn Leu Val Ser Ile Thr Arg Lys Tyr Gln Gln Asn Gly Val Asp785 790 795 800

ate ccc age gcc cag ccc ggc ggc gac acc ate tcg tcc tgc ccg tcc 2448

Ile Pro Ser Ala Gln Pro Gly Gly Asp Thr Ile Ser Ser Cys Pró Ser805 810 815

gcc tca gcc tac ggc ggc ctc gcc acc atg ggc aag gcc ctg age age 2496

Ala Ser Ala Tyr Gly Gly Leu Ala Thr Met Gly Lys Ala Leu Ser Ser820 825 830

ggc atg gtg ctc gtg ttc age att tgg aac gac aac age cag tac atgGly Met Val Leu Val Phe Ser Ile Trp Asn Asp Asn Ser Gln Tyr Met835 840 845

2544aac tgg ctc gac age ggc aac gcc ggc ccc tgc age age acc gag ggc 2592

Asn Trp Leu Asp Ser Gly Asn Ala Gly Pro Cys Ser Ser Thr Glu Gly850 855 860

aac cca tcc aac ate ctg gcc aac aac ccc aac acg cac gtc gtc ttc 2640

Asn Pro Ser Asn Ile Leu Ala Asn Asn Pro Asn Thr His Val Val Phe865 870 875 880

tcc aac ate cgc tgg gg-a gac att ggg tet act acg aac tcg act gcg 2688

Ser Asn Ile Arg Trp Gly Asp Ile Gly Ser Thr Thr Asn Ser Thr Ala885 890 895

ccc ccg ccc ccg cct gcg tcc age acg acg ttt tcg act aca cgg agg 2736

Pro Pro Pro Pro Pro Ala Ser Ser Thr Thr Phe Ser Thr Thr Arg Arg900 905 910

age tcg acg act tcg age age ccg age 27 63

Ser Ser Thr Thr Ser Ser Ser Pro Ser915 920

<210> 64<211> 921

<213> ι 'Seqüência artificial

<220> _______—

<223> ConstruçãoSintética________)

<400> 64

Gln Gln Asn Cys Ala Ala Leu Phe Gly Gln Cys Gly Gly Ile Gly Trp15 10 15

Ser Gly Thr Thr Cys Cys Val Ala Gly Ala Gln Cys Ser Phe Val Asn20 25 30

Asp Trp Tyr Ser Gln Cys Leu Ala Ser Thr Gly Gly Asn Pro Pro Asn35 40 45

Gly Thr Thr Ser Ser Ser Leu Val Ser Arg Thr Ser Ser Ala Ser Ser50 -55 60

Ser Val Gly Ser Ser Ser Pro Gly Gly Asn Ser Pro Thr Gly Ser Ala65 70 75 80

Ser Thr Tyr Thr Thr Thr Asp Thr Ala Thr Val Ala Pro His Ser Gln85 90 95

Ser Pro Tyr Pro Ser Ile Ala Ala Ser Ser Cys Gly Ser Trp Thr Leu100 105 110

Val Asp Asn Val Cys Cys Pro Ser Tyr Cys Ala Asn Asp Asp Thr Ser115 " 120 125Glu Ser Cys Ser Gly Cys Gly Thr Cys Thr Thr Pro Pro Ser Ala Asp130 135 140

Cys Lys Ser Gly Thr Met Tyr Pro Glu Val His His Val Ser Ser Asn145 150 155 160

Glu Ser Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr Ser Gly165 170 175

Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Gly Ser Val180 185 190

Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ala Thr Cys Asp Ala Phe195 200 205

Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Thr Gly Thr Thr Leu210 215 220

Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln Phe Trp225 230 235 240

Ser Ser Leu Pro Gly Ala Leu Asp Asn Tyr Leu Ser Cys Gly Glu Cys245 250 255

Ile Glu Leu Ile Gln Thr Lys Pro Asp Gly Thr Asp Tyr Ala Val Gly260 265 270

Glu Ala Gly Tyr Thr Asp Pro Ile Thr Leu Glu Ile Val Asp Ser Cys275 280 285

Pro Cys Ser Ala Asn Ser Lys Trp Cys Cys Gly Pro Gly Ala Asp His290 295 300

Cys Gly Glu Ile Asp Phe Lys Tyr Gly Cys Pro Leu Pro Ala Asp Ser305 310 315 320

Ile His Leu Asp Leu Ser Asp Ile Ala Met Gly Arg Leu Gln Gly Asn325 330 335

Gly Ser Leu Thr Asn Gly Val Ile Pro Thr Arg Tyr Arg Arg Val Gln340 345 350

Cys Pro Lys Val Gly Asn Ala Tyr Ile Trp Leu Arg Asn Gly Gly Gly355 360 365Pro Tyr Tyr Phe Ala Leu Thr Ala Val Asn Thr Asn Gly Pro Gly Ser370 375 380

Val Thr Lys Ile Glu Ile Lys Gly Ala Asp Thr Asp Asn Trp Val Ala385 390 395 400

Leu Val His Asp Pro Asn Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr405 410 415

Gly Ser Trp Val Ile Pro Gln Gly Ser Gly Pro Phe Asn Leu Pro Val420 425 430

Gly Ile Arg Leu Thr Ser Pro Thr Gly Glu Gln Ile Val Asn Glu Gln435 440 445

Ala Ile Lys Thr Phe Thr Pro Pro Ala Thr Gly Asp Pro Asn Phe Tyr450 455 460

Tyr Ile Asp Ile Gly Val Gln Phe Ser Gln Asn Gly Ser Thr Tyr Ser465 470 475 480

Ser Gly Ser Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr485 490 495

Thr Thr Lys Ala Thr Ser Thr Thr Leu Lys Thr Thr Ser Thr Thr Ser500 505 510

Ser Gly Ser Ser Ser Thr Ser Ala Ala Gln Gln Pro Gly Thr Ser Thr515 520 525

Pro Glu Val His Pro Lys Leu Thr Thr Tyr Lys Cys Thr Lys Ser Gly530 535 540

Gly Cys Val Ala Gln Asp Thr Ser Val Val Leu Asp Trp Asn Tyr Arg545 550 555 560

Trp Met His Asp Ala Asn Tyr Asn Ser Cys Thr Val Asn Gly Gly Val565 570 575

Asn Thr Thr Leu Cys Pro Asp Glu Ala Thr Cys Gly Lys Asn Cys Phe580 585 590

Ile Glu Gly Val Asp Tyr Ala Ala Ser Gly Val Thr Thr Ser Gly Ser595 600 605Ser Leu Thr Met Asn Gln Tyr Met Pro Ser Ser Ser Gly Gly Tyr Ser610 615 620

Ser Val Ser Pro Arg Leu Tyr Leu Leu Asp Ser Asp Gly Glu Tyr Val625 630 635 640

Met Leu Lys Leu Asn Gly Gln Glu Leu Ser Phe Asp Val Asp Leu Ser645 650 . 655

Ala Leu Pro Cys Gly Glu Asn Gly Ser Leu Tyr Leu Ser Gln Met Asp660 665 670

Glu Asn Gly Gly Ala Asn Gln Tyr Asn Thr Ala Gly Ala Asn Tyr Gly675 680 685

^er Gly Tyr Cys Asp Ala Gln Cys Pro Val Gln Thr Trp Arg Asn Gly690 695 700

Thr Leu Asn Thr Ser His Gln Gly Phe Cys Cys Asn Glu Met Asp Ile705 710 715 720

Leu Glu Gly Asn Ser Arg Ala Asn Ala Leu Thr Pro His Ser Cys Thr725 .730 735

Ala Thr Ala Cys Asp Ser Ala Gly Cys Gly Phe Asn Pro Tyr Gly Ser740 745 750

Gly Tyr Lys Ser Tyr Tyr Gly Pro Gly Asp Thr Val Asp Thr Ser Lys755 760 765

ir Phe Thr Ile Ile Thr Gln Phe Asn Thr Asp Asn Gly Ser Pro Ser770 775 780

Gly Asn Leu Val Ser Ile Thr Arg Lys Tyr Gln Gln Asn Gly Val Asp785 790 795 800

Ile Pro Ser Ala Gln Pro Gly Gly Asp Thr Ile Ser Ser Cys Pro Ser805 810 815

Ala Ser Ala Tyr Gly Gly Leu Ala Thr Met Gly Lys Ala Leu Ser Ser820 825 830

Gly Met Val Leu Val Phe Ser Ile Trp Asn Asp Asn Ser Gln Tyr Met835 840 845

Asn Trp Leu Asp Ser Gly Asn Ala Gly Pro Cys Ser Ser Thr Glu Gly850 855 860

Asn Pro Ser Asn Ile Leu Ala Asn Asn Pro Asn Thr His Val Val Phe865 870 875 880

Ser Asn Ile Arg Trp Gly Asp Ile Gly Ser Thr Thr Asn Ser Thr Ala885 890 895

Pro Pro Pro Pro Pro Ala Ser Ser Thr Thr Phe Ser Thr Thr Arg Arg900 905 910

Ser Ser Thr Thr Ser Ser Ser Pro Ser915 920

<210> 65U-> 2ZZ9

<213> SequênvcialaMficml"l~

<220>

<223> Proteinat de-fusao-

<220>

<221> CDS<222> (1)..(2229)

<400> 65

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr

1 5 10 15

48

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aacThr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

96

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca actSer Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

144

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acgThr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser.Ser Ser Ala Asn Thr50 55 60

192

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cagSer Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

240

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct etcAsn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

288

gtt gat aac gtt tgc tgc cca tac tac tgt etc tcg gat aat gaa tccVal Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

336gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly CysGly Ser Pro Asp Ser115 120 125

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 432

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 480

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 576

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

fc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

La Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gea tcc ggc aat ccc gac aac tac ctc tet 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 7 68

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc etc gag gta 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

fta gac age tgt ccc tgc aat gcc aat 'tca aaa tgg tgc tgt aag cgg 8 64

"Vai Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp. Cys Cys Lys Arg275 280 28.5

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro .Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc. 1008Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu'370 375 380

age gcg gtc aat acc aac ggc çcc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro .420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 134 4

^n Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat at.t gat ctg gga gtg 14 0

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc gcc tcc acg caa ggc ate tcc gaa gac ctc tac aat cgc 1488

Gln Phe Thr Ala Ser Thr Gln Gly Ile Ser Glu Asp Leu Tyr Asn Arg485 490 495

ttg gta gag atg gcc act ate tcc caa gcc gcc tac gcc gac cta tgc 1536

Leu Val Glu Met Ala Thr Ile Ser Gln Ala Ala Tyr Ala Asp Leu Cys500 505 510

aat att cca tcg act att ate aaa gga gag aaa att tac aac gct caa 158 4

sn Ile Pro Ser Thr Ile Ile Lys Gly Glu Lys Ile Tyr Asn Ala Gln515 520 525

act gat ate aac gga tgg ate ctc cgc gac gac acc age aaa gaa att 1632

Thr Asp Ile Asn Gly Trp Ile Leu Arg Asp Asp Thr Ser Lys Glu Ile530 535 540

ate acc gtc ttc cgt ggc act ggc agt gac aca aac cta cag ctc gat 1680

Ile Thr Val Phe Arg Gly Thr Gly Ser Asp Thr Asn Leu Gln Leu Asp545 550 555 560

act aac tac acg ctc acg cca ttc gac act cta cct caa tgc aac gat 1728

Thr Asn Tyr Thr Leu Thr Pro Phe Asp Thr Leu Pro Gln Cys Asn Asp

565 570 575

tgc gag gta cac ggt gga tac tat att gga tgg ate tca gtc caa gac 177 6

Cys Glu Val His Gly Gly Tyr Tyr Ile Gly Trp Ile Ser Val Gln Asp530 585 590

caa gtc gag tcg ctt gtc aaa caa cag gct age cag tat ccg gac tatGln Val Glu Ser Leu Val Lys Gln Gln Ala Ser Gln Tyr Pro Asp Tyr

1824595 600 605

gcg ctt acc gtg aca ggc cat agt ctg gga gcg tcg atg gca gca ctc 1872

Ala Leu Thr Val Thr Gly His Ser Leu Gly Ala Ser Met Ala Ala Leu610 615 620

act gcc gcc cag ctg tcc gcg aca tac gac aac gtc cgt ctg tac aca 1920

Thr Ala Ala Gln Leu Ser Ala Thr Tyr Ãsp Asn Val Arg Leu Tyr Thr625 630 635 640

ttc ggc gaa ccg cgc age ggc aac cag gcc ttc gcg tcg tac atg aac 1968

Phe Gly Glu Pro Arg Ser Gly Asn Gln Ala Phe Ala Ser Tyr Met Asn645 650 655

gat gcg ttc cag gtc tcg age ccg gag acg acc cag tac ttc cgg gtc 2016

Asp Ala Phe Gln Val Ser Ser Pro Glu Thr Thr Gln Tyr Phe Arg Val660 665 670

act cat tcc aac gac ggc ate cca aac ttg ccc ccg gcg gac gag ggt 2064

^hr His Ser Asn Asp Gly Ile Pro Asn Leu Pro Pro Ala Asp Glu Gly675 680 685

tac gcc cat ggt ggt gta gag tac tgg age gtt gat cct tac age gcc 2112

Tyr Ala His Gly Gly Vai Glu Tyr Trp Ser Val Asp Pro Tyr Ser Ala690 695 700

cag aac acg ttt gtc tgt act ggg gat gaa gta cag tgc tgt gag gcaGln Asn Thr Phe Val Cys Thr Gly Asp Glu Val Gln Cys Cys Glu Ala705 710 715 720

2160

cag ggc gga cag ggg gtg aat gat gcg cat act act tat ttt ggg atg 2208Gln Gly Gly Gln Gly Val Asn Asp Ala His Thr Thr Tyr Phe Gly Met725 730 735

acg age gga gct tgt act tgg 2229

Thr Ser Gly Ala Cys Thr Trp740

<210> 66

<211> 743

<212> PRT

<213> sequencia artificial

<220>

<223> Construção Sintética <400> 66

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr15 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu IleAsn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 -60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

\r Met Cys Lys Ser Gly Thr Met Txp Gly Glu Gln His Thr Val Thr130 1 135 14 0

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145. 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

rhr Leu Arg Gly Asn Phe-. Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 22.0

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val-260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn LeuThr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu.His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 38Ό

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Vai. Ser Met Arg Leu Thr Ala435 440 445

Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Ala Ser Thr Gln Gly Ile Ser Glu Asp Leu Tyr Asn Arg485 490 4 95

Leu Val Glu Met Ala Thr Ile Ser Gln Ala Ala Tyr Ala Asp Leu Cys500 505 510

Asn Ile Pro Ser Thr Ile Ile Lys Gly Glu Lys Ile Tyr Asn Ala Gln515 520 525

Thr Asp Ile Asn Gly Trp Ile Leu Arg Asp Asp Thr Ser Lys Glu Ile530 535 540Ile Thr Val Phe Arg Gly Thr Gly Ser Asp Thr Asn Leu Gln Leu Asp545 550 555 560

Thr Asn Tyr Thr Leu Thr Pro Phe Asp Thr Leu Pro Gln Cys Asn Asp565 570 575

Cys Glu Val His Gly Gly Tyr Tyr Ile Gly Trp Ile Ser Val Gln Asp580 585 590

Gln Val Glu Ser Leu Val Lys Gln Gln Ala Ser Gln Tyr Pro Asp Tyr595 600 605

Ala Leu Thr Val Thr Gly His Ser Leu Gly Ala Ser Met Ala Ala Leu610 615 620

f( Thr Ala Ala Gln Leu Ser Ala Thr Tyr Asp Asn Val Arg Leu Tyr Thr625 630 635 640

Phe Gly Glu Pro Arg Ser Gly Asn Gln Ala Phe Ala Ser Tyr Met Asn645 650 655

Asp Ala Phe Gln Val Ser Ser Pro Glu Thr Thr Gln Tyr Phe Arg Val660 665 670

Thr His Ser Asn Asp Gly Ile Pro Asn Leu Pro Pro Ala Asp Glu Gly675 680 685

Tyr Ala His Gly Gly Val Glu Tyr Trp Ser Val Asp Pro Tyr Ser Ala690 695 700

Gln Asn Thr Phe Val Cys Thr Gly Asp Glu Val Gln Cys Cys Glu Ala705 710 715 720

Gln Gly Gly Gln Gly Val Asn Asp Ala His ThrThr Tyr Phe Gly Met725 730 735

Thr Ser Gly Ala Cys Thr Trp740

<210> 67<211> 2367<212> DNA<213> Seqüência artificial<220><223> Proteína de fusão<220>

<221> CDS

<222> (1)..(2367)

<400> 67

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat 4 8

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac 96

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys -Ala Glu Ile Asn20 25 30

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca act 14 4

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

?c aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acg 192

r Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cag 240

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 7 5 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct etc 288

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser-" 100 105 110

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

;cc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 432

'Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 480

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg'age tgg aca gac cca atg ctg ggc tet acc tgc gac 57 6

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gca tcc ggc aat ccc" gac aac tac ctc tct 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gtá 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 864

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

>ro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gca gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

^le Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 -375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser.Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val- Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tct tgg gtc ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 1344

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg.Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc ggc tcg act tac tcc agt gga tct tct tcg ggg tcg ggg 1488Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

tct age tcc age tcg agt tcg act acc act aag gcc act tcg acg acc. 1536Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

ttg aag act acc tcg acc acc age agt gga age agt tcg aca tcg gcg 158 4

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

gcg gcc tcc acg caa ggc ate tcc gaa gac ctc tac aat cgc ttg gta 1632

Ala Ala Ser Thr Gln Gly Ile Ser Glu Asp Leu- Tyr Asn Arg Leu Val530 535 540

gag atg gcc act ate tcc caa gcc gcc tac gcc gac cta tgc aat att 1680

Glu Met Ala Thr Ile Ser Gln Ala Ala Tyr Ala Asp Leu Cys Asn Ile545 550 555 560

cca tcg act att ate aaa gga gag aaa att tac aac gct caa act gat 1728

Pro Ser Thr Ile Ile Lys Gly Glu Lys Ile Tyr Asn Ala Gln Thr Asp565 570 575

ate aac gga tgg ate ctc cgc gac gac acc age aaa gaa att ate acc 1776Ile Asn Gly Trp Ile Leu Arg Asp Asp Thr Ser Lys Glu Ile Ile Thr580 585 590

gtc ttc cgt.ggc act ggc agt gac aca aac cta cag ctc gat act aac 1824

Val Phe Arg Gly Thr Gly Ser Asp Thr Asn Leu Gln Leu Asp Thr Asn595 600 605

tac acg ctc acg cca ttc gac act cta cct caa tgc aac gat tgc gag 1872

Tyr Thr Leu Thr Pro Phe Asp Thr Leu Pro Gln Cys Asn Asp Cys Glu610 615 620

gta cac ggt gga tac tat att gga tgg ate tca gtc caa gac caa gtc 1920

Val His Gly Gly Tyr Tyr Ile Gly Trp Ile Ser Val Gln Asp Gln Val625 630 635 640

gag tcg ctt gtc aaa caa cag gct age cag tat ccg gac tat gcg ctt 1968

Glu Ser Leu Val Lys Gln Gln Ala Ser Gln Tyr Pro Asp Tyr Ala Leu645 650 655

acc gtg aca ggc cat agt ctg gga gcg tcg atg gea gea ctc act gcc 2016

Thr Val Thr Gly His Ser Leu Gly Ala Ser Met Ala Ala Leu Thr Ala660 665 670

gcc cag ctg tcc gcg aca tac gac aac gtc cgt ctg tac aca ttc ggc 2064

Ala Gln Leu Ser Ala Thr Tyr Asp Asn Val Arg Leu Tyr Thr Phe Gly675 680 685

gaa ccg cgc age ggc aac cag gcc ttc gcg tcg tac atg aac gat gcgGlu Pro Arg Ser Gly Asn Gln Ala Phe Ala Ser Tyr Met Asn Asp Ala690 695 700ttc cag gtc tcg age ccg gag acg acc cag tac ttc cgg gtc act cat 2160

Phe Gln Val Ser Ser Pro Glu Thr Thr Gln Tyr Phe Arg Val.Thr His705 710 715 720

tcc aac gac ggc ate cca aac ttg ccc ccg gcg gac gag ggt tac gcc 2208

Ser Asn Asp Gly Ile Pro Asn Leu Pro Pro Ala Asp Glu Gly Tyr Ala725 730 735

cat ggt ggt gta gag tac tgg age gtt gat cct tac age gcc cag aac 2256

His Gly Gly Val Glu Tyr Trp Ser Val Asp Pro Tyr Ser Ala Gln Asn740 745 750

acg ttt gtc tgt act ggg gat gaa gta cag tgc tgt gag gea cag ggc 2304

Thr Phe Val Cys Thr Gly Asp Glu Val Gln Cys Cys Glu Ala Gln Gly755 760 765

gga cag ggg gtg aat gat gcg cat act act tat ttt ggg atg acg age 2352Gly Gln Gly Val Asn Asp Ala His Thr Thr Tyr Phe Gly Met Thr Ser770 775 780

jga gct tgt act tgg 2367

'Gly Ala Cys Thr Trp7 8 5

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Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr .Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 ' 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe. Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 -v 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 . 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu-Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Gly Ser. Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

Ala Ala Ser Thr Gln Gly Ile Ser Glu Asp Leu Tyr Asn Arg Leu Val530 535 540

Glu Met Ala Thr Ile Ser Gln Ala Ala Tyr Ala AspLeu Cys Asn Ile545 550 555 560

Pro Ser Thr Ile Ile Lys Gly Glu Lys Ile Tyr Asn Ala Gln Thr Asp565 570 575

Ile Asn Gly Trp Ile Leu Arg Asp Asp Thr Ser Lys Glu Ile Ile Thr580 585 590Val Phe Arg Gly Thr Gly Ser Asp Thr Asn Leu Gln Leu Asp Thr Asn595 600 605

Tyr Thr Leu Thr Pro Phe Asp Thr Leu Pro Gln Cys Asn Asp Cys Glu610 615 620

Val His Gly Gly Tyr Tyr Ile Gly Trp Ile Ser Val Gln Asp Gln Val625 630 635 640

Glu Ser Leu Val Lys Gln Gln Ala Ser Gln Tyr Pro Asp Tyr Ala Leu645 650 655

Thr Val Thr Gly His Ser Leu Gly Ala Ser Met Ala Ala Leu Thr Ala660 665 670

ÊbJLa Gln Leu Ser Ala Thr Tyr Asp Asn Val Arg Leu Tyr Thr Phe Gly 675 680 685

Glu Pro Arg Ser Gly Asn Gln Ala Phe Ala Ser Tyr Met Asn Asp Ala690 695 700

Phe Gln Val Ser Ser Pro Glu Thr Thr Gln Tyr Phe Arg Val Thr His705 710 715 720

Ser Asn Asp Gly Ile Pro Asri Leu Pro Pro Ala Asp Glu Gly Tyr Ala725 730 735

His Gly Gly Val Glu Tyr Trp Ser Val Asp Pro Tyr Ser Ala Gln Asn740 745 750

JThr Phe Val Cys Thr Gly Asp Glu Val Gln Cys Cys Glu Ala Gln Gly755 760 765

Gly Gln Gly Val Asn Asp Ala His Thr Thr Tyr Phe Gly Met Thr Ser770 775 780

Gly Ala Cys Thr Trp785

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cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat 48

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 '15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac 96

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca act 14 4

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acg 192

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gca aca cag 240

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctc 288

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys^Gly Ser Pro Asp Ser115 120 ~ 125.

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 432

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 480

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 576

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tvr Tyr Thr Gln210 . 215 220ttc tgg cct tcc ctg gct gca tcc ggc aat ccc gac aac tac ctc tct 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 8 64

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aga cca ggc ggc age ggc gca gac cac tgc ggc gaa ate gac ttc 960

hr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys ProGly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu

370 375 380

gc gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn4.05 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tct tgg gtc ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 1344

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg

1440Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc gcg acc gac ccc ttc cag tcg cgg tgc aat gaa ttc cag 1488

Gln Phe Thr Ala Thr Asp Pro Phe Gln Ser Arg Cys Asn Glu Phe Gln485 490 495

aac aag ate gac ate gcc aat gtc acc gtc aga tcg gtc gea tac gtt 1536

Asn Lys Ile Asp Ile Ala Asn Val Thr Val Arg Ser Val Ala Tyr Val500 505 510

gct gct gga cag aac ate tcc caa gcg gag gtc gcc tcc gtg tgt aaa 1584

Ala Ala Gly Gln Asn Ile Ser Gln Ala Glu Val Ala Ser Val Cys Lys515 520 525

gea tcg gtt caa gcc agt gtc gac ctg tgc cgg gta acc atg aac ate 1632

Ala Ser Val Gln Ala Ser Val Asp Leu Cys Arg Val Thr Met Asn Ile530 535 540

tcg acg tcg gat cgc age cat ctg tgg gct gag gçc tgg ctc cca aga 1680

Ser Thr Ser Asp Arg Ser His Leu Trp Ala Glu Ala Trp Leu Pro Arg545 550 555 560

aat tat acc ggt cgc ttc gtg age acg ggg aat gga ggt cta gcc ggc 1728

Asn Tyr Thr Gly Arg Phe Val Ser Thr Gly Asn Gly Gly Leu Ala Gly565 570 575

tgt gtc caa gaa acg gac ctc aac ttt gea gcc aac ttt ggt ttc gct 1776Cys Val Gln Glu Thr Asp Leu Asn Phe Ala Ala Asn Phe Gly Phe Ala580. 585 590

acc gtg ggc acc aac ggt gga cat gac ggg gac acg gcc aaa tac ttc 1824Thr Val Gly Thr Asn Gly Gly His Asp Gly Asp Thr Ala' Lys Tyr Phe595 600 605

ctc aac aac tcg gag gtt ctg gcc gat ttt gcc tat cgc tca gtg cac 1872

Leu Asn Asn Ser Glu Val Leu Ala Asp Phe Ala Tyr Arg Ser Val His610 615 620

gaa ggg acc gtg gtg ggt aag caa cta act caa ttg ttt tat gac gag 1920Glu Gly Thr Val Val Gly Lys Gln Leu Thr Gln Leu Phe Tyr Asp Glu625 630 635 640

gga tac aac tac tcc tac tat ttg ggt tgc tcc acc gga ggc cgc caa 1968

Gly Tyr Asn Tyr Ser Tyr Tyr Leu Gly Cys Ser Thr Gly Gly Arg Gln645 650 655

ggc tac cag caa gtc caa cgg ttt ccc gac gac tat gac gga gtg att 2016

Gly Tyr Gln Gln Val Gln Arg Phe Pro Asp Asp Tyr Asp Gly Val Ile660 665 670

gcg ggc tcc gea gcg atg aac ttt ate aac ctg ate tcc tgg ggg gccAla Gly Ser Ala Ala Met Asn Phe Ile Asn Leu Ile Ser Trp Gly Ala675 680 685

2064

ttc ttg tgg aag gcg acg ggg tta gcg gat gat cca gac ttt ate tet 2112

Phe Leu Trp Lys Ala Thr Gly Leu Ala Asp Asp Pro Asp Phe Ile Ser690 695 700

gea aac ctg tgg tcc gta ate cac cag gag att gtt cgt cag tgc gacAla Asn Leu Trp Ser Val Ile His Gln Glu Ile Val Arg Gln Cys Asp

2160705 710 715 720

ctg gtc gat ggg gct ctg gat gga ate ate gaa gac cct gat ttc tgt 2208

Leu Val Asp Gly Ala Leu Asp Gly Ile Ile Glu Asp Pro Asp Phe Cys725 730 735

gct cca gtc ate gag cgc ttg ate tgc gac ggg act acc aac ggc acc 2256Ala Pro Val Ile Glu Arg Leu Ile Cys Asp Gly Thr Thr Asn Gly Thr740 745 750

tet tgt ate acg gga gcc cag gea gea aag gtc aac cgg gcc ttg agt 2304

Ser Cys Ile Thr Gly Ala Gln Ala Ala Lys Val Asn Arg Ala Leu Ser755 760 765

gac ttc tat ggc ccc gac ggg aca gtg tac tac ccg cgc ctg aac tat 2352

Asp Phe Tyr Gly Pro Asp Gly Thr Val Tyr Tyr Pro Arg Leu Asn Tyr770 775 780

ggg- ggt gag gcc gac tcg gct tcc ctg tac ttc acg ggg tcg atg tac 2400

Gly Gly Glu Ala Asp Ser Ala Ser Leu Tyr Phe Thr Gly Ser Met Tyr785 790 795 800

age cgt acg gag gaa tgg tac aaa tat gtg gtc tat aac gac acc aac 2448

Ser Arg Thr Glu Glu Trp Tyr Lys Tyr Val Val Tyr Asn Asp Thr Asn805 810 8.15

tgg aac tcc age cag tgg acg ctg gag agt gcc aag ctg gcc ctg gag 2496

Trp Asn Ser Ser Gln Trp Thr Leu Glu Ser Ala Lys Leu Ala Leu Glu820 825 830

cag aat ccg ttc aat ate cag gcg ttt gat ccc aac ate acg gcc ttc 2544

Gln Asn Pro Phe Asn Ile Gln Ala Phe Asp Pro Asn Ile Thr Ala Phe835 840 845

cgg gac cgg ggt ggc aag ctg ctg tcc tac cac ggc acg cag gat ccc 2592Arg Asp Arg Gly Gly Lys Leu Leu Ser Tyr His Gly Thr Gln Asp Pro850 855 : 860

att ate age tcc acg gat age aag ctc tac tac cga cgg gta, gcg aat 2640

Ile Ile Ser Ser Thr Asp Ser Lys Leu Tyr Tyr Arg Arg Val Ala Asn865 870 875 880

gcc ctg aat gcc gcg ccg tcc gag cta gat gag ttc tat cgg ttc ttc 2688

Ala Leu Asn Ala Ala Pro Ser Glu Leu Asp Glu Phe Tyr Arg Phe Phe885 890 895

cag ate tcc ggc atg ggc cac tgt ggc gat ggc acg gga gea tcg tac 2736

Gln Ile Ser Gly Met Gly His Cys Gly Asp Gly Thr Gly Ala Ser Tyr900 905 910

ate ggc cag gga tat ggc acg tac acc tcc aag gcg ccc caa gtc aac 2784

Ile Gly Gln Gly Tyr Gly Thr Tyr Thr Ser Lys Ala Pro Gln Val Asn915 920 925

ctg ctg cgc acg atg gtg gac tgg gtg gaa aac gga aag gcg ccc gagLeu Leu Arg Thr Met Val Asp Trp Val Glu Asn Gly Lys Ala Pro Glu930 935 940

2832

tat atg ccg ggc aac aag ctc aac gcg aac ggg tca att gag tac atg 2880

Tyr Met Pro Gly Asn Lys Leu Asn Ala Asn Gly Ser Ile Glu Tyr Met945 950 955 960cgc aag cac tgc cgg tat ccg aag catArg Lys His Cys Arg Tyr Pro Lys His965

aac tac acc gat cct aac tcc tgg actAsn Tyr Thr Asp Pro Asn Ser Trp Thr980 985

aac att cac acg ggg ccg ggt 2928

Asn Ile His Thr Gly Pro Gly970 975

tgc gta 2961

Cys Val

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Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 4 0 4 5

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala· Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 '300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Ala Thr Asp Pro Phe Gln Ser Arg Cys Asn. Glu Phe Gln485 490 495

Asn Lys Ile Asp Ile Ala Asn Val Thr Val Arg Ser Val Ala Tyr Val500 505 510

Ala Ala Gly Gln Asn Ile Ser Gln Ala Glu Val Ala Ser Val Cys Lys515 520 525

Ala Ser Val Gln Ala Ser Val Asp Leu Cys Arg Val Thr Met Asn Ile530 535 540

Ser Thr Ser Asp Arg Ser His Leu Trp Ala Glu Ala Trp Leu Pro Arg545 550 555 560

Asn Tyr Thr Gly Arg Phe Val Ser Thr Gly Asn Gly Gly Leu Ala Gly.565 570 575

Cys Val Gln Glu Thr Asp Leu Asn Phe Ala Ala Asn Phe Gly Phe Ala580 585 590

Thr Val Gly Thr Asn Gly Gly His Asp Gly Asp Thr Ala Lys Tyr Phe595 600 605

Leu Asn Asn Ser Glu Val Leu Ala Asp Phe Ala Tyr Arg Ser Val His610 ' 615 620

Glu Gly Thr Val Val Gly Lys Gln Leu Thr Gln Leu Phe Tyr Asp Glu625 630 635 640

Gly Tyr Asn Tyr Ser Tyr Tyr Leu Gly Cys Ser Thr Gly Gly Arg Gln645 650 655Gly Tyr Gln Gln -Val Gln Arg Phe Pro Asp Asp Tyr Asp Gly Val Ile660 665 670

Ala Gly Ser Ala Ala Met Asn Phe Ile Asn Leu Ile Ser Trp Gly Ala675 680 685

Phe Leu Trp Lys Ala Thr Gly Leu Ala Asp Asp Pro Asp Phe Ile Ser690 695 700

Ala Asn Leu Trp Ser Val Ile His Gln Glu Ile Val Arg Gln Cys Asp705 710 715 720

Leu Val Asp Gly Ala Leu Asp Gly Ile Ile Glu Asp Pro Asp Phe Cys725 730 735

Ala Pro Val Ile Glu Arg Leu He. Cys Asp Gly Thr Thr Asn Gly Thr740 745 750

Ser Cys Ile Thr Gly Ala Gln Ala Ala Lys Val Asn Arg Ala Leu Ser755 760 765

Asp Phe Tyr Gly Pro Asp Gly Thr Val Tyr Tyr Pro Arg Leu Asn Tyr770 775 780

Gly Gly Glu Ala As,p Ser Ala Ser Leu Tyr Phe Thr Gly Ser Met Tyr785 790 795 800

Ser Arg Thr Glu Glu Trp Tyr Lys Tyr Val Val Tyr Asn Asp Thr Asn805 810 815

Trp Asn Ser Ser Gln Trp Thr Leu Glu Ser Ala Lys Leu Ala Leu Glu820 825 830

Gln Asn Pro Phe Asn Ile Gln Ala Phe Asp Pro Asn Ile Thr Ala Phe835 840 845

Arg Asp Arg Gly Gly Lys Leu Leu Ser Tyr His Gly Thr Gln Asp Pro850 855 860

Ile Ile Ser Ser Thr Asp Ser Lys Leu Tyr Tyr Arg Arg Val Ala Asn865 870 875 880

Ala Leu Asn Ala Ala Pro Ser Glu Leu Asp Glu Phe Tyr Arg Phe Phe885 890 895Gln Ile Ser-Gly Met Gly His Cys Gly Asp Gly Thr Gly Ala Ser Tyr900 905 910

311

Ile Gly Gln Gly Tyr Gly Thr Tyr Thr Ser Lys Ala Pro Gln Val Asn915 920 925'

Leu Leu Arg Thr Met Val Asp Trp Val Glu Asn Gly Lys Ala Pro Glu930 935 940

Tyr Met Pro Gly Asn Lys Leu Asn Ala Asn Gly Ser Ile Glu Tyr Met945 950 . 955 960

Arg Lys His Cys Arg Tyr Pro Lys His Asn Ile His Thr Gly Pro Gly965 970 975

Asn Tyr Thr Asp Pro Asn Ser Trp Thr Cys Val980 985

<210> 71

<211> 3099

<212> DNA

<213> Seqüência artificial

<220>

<223> Prõteína dé fusão

<220>

<221> CDS

<222> (1)..(3099)

<400> 71

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat 48

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac 96

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

tçg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca act 144

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acg 192

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cag 240

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln 65 70 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct etc 288

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336

Val Asp Asn. Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 432

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 480

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 57 6

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gea tcc ggc aat ccc gac aac tac ctc tet 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 7 68

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp.245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta. 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta.gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 864

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc. ggc age ggc gea gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac.ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tccLys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

1008gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt .gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 124 8

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

:ac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296

Pyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 134 4

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe.Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc ggc tcg act tac tcc agt gga tet tet tcg ggg tcg ggg 1488

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

ct age tcc age tcg agt tcg act acc act aag gcc act tcg acg acc. 1536rSer Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

ttg aag act acc tcg acc acc age agt gga age agt tcg aca tcg gcg 1584

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

gcg gcg acc gac ccc ttc cag tcg cgg tgc aat gaa ttc cag aac aag 1632

Ala Ala Thr Asp Pro Phe Gln Ser Arg Cys Asn Glu Phe Gln Asn Lys530 535 540

ate gac ate gcc aat gtc acc gtc aga tcg gtc gea tac gtt gct gct 1680

Ile Asp Ile Ala Asn Val Thr Val Arg Ser Val Ala Tyr Val Ala Ala545 550 555 560

gga cag.aac ate tcc caa gcg gag gtc gcc tcc gtg tgt aaa gea tcg 1728

Gly Gln Asn Ile Ser Gln Ala Glu Val Ala Ser Val Cys Lys Ala Ser565 570 575

gtt caa gcc agt gtc gac ctg tgc cgg gta acc atg aac ate tcg acg 1776Val Gln Ala Ser Val Asp Leu Cys Arg Val Thr Met Asn Ile Ser Thr580 585 590

tcg gat cgc age cat ctg tgg gct gag gcc tgg ctc cca aga aat tat 1824

Ser Asp Arg Ser His Leu Trp Ala Glu Ala Trp Leu Pro Arg Asn Tyr595 600 605

acc ggt cgc ttc gtg age acg ggg aat gga ggt cta gcc ggc tgt gtc 1872

Thr Gly Arg Phe Val Ser Thr Gly Asn Gly. Gly Leu Ala Gly Cys Val610 615 620

caa gaa acg gac ctc aac ttt gea gcc aac ttt ggt ttc gct acc gtg 1920

Gln Glu Thr Asp Leu" Asn.Phe Ala Ala Asn Phe Gly Phe Ala Thr Val625 630 635 640

ggc acc aac ggt gga cat gac ggg gac acg gcc aaá tac ttc ctc aac 1968

Gly Thr Asn Gly Gly His Asp Gly Asp Thr Ala Lys Tyr Phe Leu Asn645 650 655

aac tcg gag gtt ctg gcc gat ttt gcc tat cgc tca gtg cac gaa ggg 2016

Asn Ser Glu Val Leu Ala Asp Phe Ala Tyr Arg Ser Val His Glu Gly660 665 670

acc gtg gtg ggt aag caa cta act caa ttg ttt tat gac gag gga tac 2064

Thr Val Val Gly Lys Gln Leu Thr Gln Leu Phe Tyr Asp Glu Gly Tyr675 680 685

aac tac tcc tac tat ttg ggt tgc.tcc acc gga ggc cgc caa ggc tac 2112

Asn Tyr Ser Tyr Tyr Leu Gly Cys Ser Thr Gly Gly Arg Gln Gly Tyr690 695 700

cag caa gtc caa cgg ttt ccc gac gac tat gac gga gtg att gcg ggc 2160

Gln Gln Val Gln Arg Phe Pro Asp Asp Tyr Asp Gly Val Ile Ala Gly705 710 715 720

tcc gea gcg atg aac ttt ate aac ctg ate tcc tgg ggg gcc ttc ttg 2208

Ser Ala Ala Met Asn Phe Ile Asn Leu Ile Ser Trp Gly Ala Phe Leu725 730 735

tgg aag gcg acg ggg tta gcg gat gat cca gac ttt ate tet gea aac 2256

Trp Lys Ala Thr Gly Leu Ala Asp Asp Pro Asp Phe Ile Ser Ala Asn740 745 750

ctg tgg tcc gta ate cac cag gag att gtt cgt cag tgc gac ctg gtc 2304

Leu Trp Ser Val Ile His Gln Glu Ile Val Arg Gln Cys Asp Leu Val755 760 765

gat ggg gct ctg gat gga ate ate gaa gac cct gat ttc tgt gct cca 2352

Asp Gly Ala Leu Asp Gly Ile Ile Glu Asp Pro Asp Phe Cys Ala Pro770 775 780

gtc ate gag cgc ttg ate tgc gac ggg act acc aac ggc acc tet tgt 2400

Val Ile Glu Arg Leu Ile Cys Asp Gly Thr Thr Asn Gly Thr Ser Cys785 790 795 800

ate acg gga gcc cag gea gea aag gtc aac cgg gcc ttg agt gac ttc 2448

Ile Thr Gly Ala Gln Ala Ala Lys Val Asn Arg Ala Leu Ser Asp Phe805 810 815

tat ggc ccc gac ggg aca gtg tac tac ccg cgc ctg aac tat ggg ggt 2496Tyr Gly Pro Asp Gly Thr Val Tyr Tyr Pro Arg Leu Asn Tyr Gly Gly820 825 830

gag gcc gac tcg gct tcc ctg tac ttc acg ggg tcg atg tac age cgt 2544

Glu Ala Asp Ser Ala Ser Leu Tyr Phe Thr Gly Ser Met Tyr Ser Arg835 840 845

acg gag gaa tgg tac aaa tat gtg gtc tat aac gac acc aac tgg aac 2592

Thr Glu Glu Trp Tyr Lys Tyr Val Val Tyr Asn Asp Thr Asn Trp Asn850 855 860

tcc age cag tgg acg ctg gag agt gcc aag ctg gcc ctg gag cag aat 2640

Ser Ser Gln Trp Thr Leu Glu Ser Ala Lys Leu Ala Leu Glu Gln Asn865 870 875 880

ccg ttc aat ate cag gcg ttt gat ccc aac ate acg gcc ttc cgg gac- 2688Pro Phe Asn Ile Gln Ala Phe Asp Pro Asn Ile Thr Ala Phe Arg Asp885 890 895

c99 gÇTt ggc aag ctg ctg tcc tac cac ggc acg cag gat ccc att ate 2736 -

Arg Gly Gly Lys Leu Leu Ser Tyr His Gly Thr Gln Asp Pro Ile Ile900 905 910

age tcc acg gat age aag ctc tac tac cga cgg gta gcg aat gcc ctg 2784

Ser Ser Thr Asp Ser Lys Leu Tyr Tyr Arg Arg Val Ala Asn Ala Leu915 920 925

aat gcc gcg ccg tcc gag cta gat gag ttc tat cgg ttc ttc cag ate 2832

Asn Ala Ala Pro Ser Glu Leu Asp Glu Phe Tyr Arg Phe Phe Gln Ile930 935 940

tcc ggc atg ggc cac tgt ggc gat ggc acg gga gea tcg tac ate ggc 2880

Ser Gly Met Gly -His Cys Gly Asp Gly Thr Gly Ala Ser Tyr Ile Gly .945 950 955 960

cag gga tat ggc acg tac acc tcc aag gcg ccc caa gtc aac ctg ctg 2 928

Gln Gly Tyr Gly Thr Tyr Thr Ser Lys Ala Pro Gln Val Asn Leu Leu965 970 975

cgc acg atg gtg gac tgg gtg gaa aac gga aag gcg ccc gag tat atg 2976

Arg Thr Met Val Asp Trp Val Glu Asn Gly Lys Ala Pro Glu Tyr Met980 985 990

ccg ggc aac aag ctc aac gcg aac ggg tca att gag tac atg cgc aag . 3024Pro Gly Asn Lys Leu Asn Ala Asn Gly Ser Ile Glu Tyr Met Arg Lys995 1000 1005

cac tgc cgg tat ccg aag cat aac att cac acg ggg ccg ggt aac 3069

His Cys Arg Tyr Pro Lys His Asn Ile His Thr Gly Pro Gly Asn 1010 1015 1020

tac acc gat cct aac tcc tgg act tgc gta 3099

Tyr Thr Asp Pro Asn Ser Trp Thr Cys Val1025 1030

<210> 72

<211> 1033

<212> PRT

<213> Seqüência artificiai<220><223> Construção Sintética<400> 72

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser. Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

3er Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 ' 95 .

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185' 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe"" )5 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

^er Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val15 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser485 490

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr500 505

Gly Ser Gly495

Ser Thr Thr510

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser515 520 525

;<Thr Ser Ala

Ala Ala Thr Asp Pro Phe Gln Ser Arg Cys Asn Glu Phe530 535 540

ι Gln Asn Lys

Ile Asp Ile Ala Asn Val Thr Val Arg Ser Val Ala Tyrf Val Ala Ala545 550 . 555 I 560

Gly Gln Asn Ile Ser Gln Ala Glu Val Ala Ser. Val Cysi, Lys. Ala Ser565 570 575

Val Gln Ala Ser Val Asp Leu Cys Arg Val Thr Met Asrii580 585 .

ii. Ile Ser Thr590

Ser Asp Arg Ser His Leu Trp Ala Glu Ala Trp Leu Prci Arg Asn Tyr595 : 600 ■ 605 '

Thr Gly Arg Phe Val Ser Thr Gly Asn Gly Gly Leu Ala Gly Cys Val610 615 620 , fj·

Gln Glu Thr Asp Leu Asn Phe Ala Ala Asn Phe Gly Phe Ala Thr Val625 . 630 635 f 640

Gly Thr Asn Gly Gly His Asp Gly Asp Thr Ala Lys Ty645 650

ir Phe Leu Asn655

Asn Ser Glu Val Leu Ala Asp Phe Ala Tyr Arg Ser Va660 665

Í His Glu Gly670

Thr Val Val Gly Lys Gln Leu Thr Gln Leu Phe Tyr As,p Glu Gly Tyr675 680 ; 68.5

Asn Tyr Ser Tyr Tyr Leu Gly Cys Ser Thr Gly Gly Arjg Gln Gly Tyr690 695 700

Gln Gln Val Gln Arg Phe Pro Asp Asp Tyr Asp Gly Vai Ile Ala Gly705 710 715 I 720Ser Ala Ala Met Asn Phe Ile Asn Leu Ile Ser.Trp Gly725 730 735

Trp Lys Ala Thr Gly Leu Ala Asp Asp Pro Asp Phe Il740 745 750

Leu Trp Ser Val Ile His Gln Glu Ile Val Arg Gln CyS Asp Leu Val755 760 765

Asp Gly Ala Leu Asp Gly Ile Ile Glu Asp Pro Asp Phjé Cys Ala Pro770 775 780

Val Ile Glu Arg Leu Ile Cys Asp Gly Thr Thr Asn Gly Thr Ser Cys785 790 795 800

Ile Thr Gly Ala Gln Ala Ala Lys Val Asn Arg Ala Leu Ser Asp Phe805 810 815

Tyr Gly Pro Asp Gly Thr Val Tyr Tyr Pro Arg Leu Asn Tyr Gly Gly820 825 830

Glu Ala Asp Ser Ala Ser Leu Tyr Phe Thr Gly Ser MeijL: Tyr Ser Arg835 840 845

Thr Glu Glu Trp Tyr Lys Tyr Val Val Tyr Asn Asp Thr Asn Trp Asn850 855 860

Ser Ser Gln Trp Thr Leu Glu Ser Ala Lys Leu Ala Leu Glu Gln Asn865 870 875 880

Pro Phe Asn Ile Gln Ala Phe Asp Pro Asn He- Thr AJia Phe Arg Asp885 890 895

Arg Gly Gly Lys Leu Leu Ser Tyr His Gly Thr Gln Asp Pro Ile Ile900 905 910

Ser Ser Thr Asp Ser Lys Leu Tyr Tyr Arg Arg Val Alia Asn Ala Leu915 920 925

Asn Ala Ala Pro Ser Glu Leu Asp Glu Phe Tyr Arg Phe Phe Gln Ile930 935 940

Ser Gly Met Gly His Cys Gly Asp Gly Thr Gly Ala Phe Leu Ser Ala Asn Sér Tyr Ile Gly 945 950 955 960Gln Gly Tyr Gly Thr Tyr Thr Ser Lys Ala Pro Gln Val Asn Leu Leu965 970 975

Arg Thr Met Vai. Asp Trp Val Glu Asn Gly Lys Ala Pro Glu Tyr Met980. 985 990

Pro Gly Asn Lys Leu Asn Ala Asn Gly Ser Ile Glu Tyr Met Arg Lys995 1000 1005

His Cys Arg Tyr Pro Lys His Asn Ile His Thr Gly Pro Gly Asn1010 1015 1020

Tyr Thr Asp Pro Asn Ser Trp Thr Cys Val1025 1030

<210> 7 3

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cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat 4 8

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac 96

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

tcg tac tac tac cag tgc ata cca gea aca gct gtg.agt act tca act· 144

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

acc aca gtg aca tet cec tet age tet ggt tcg tet- tet gcc aac acg 192

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cag 24 0

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80 '

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctc 288

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 .95

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110gag tcc tgc acg age age tgt.acc ggc ggc tgc ggc agtGlu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Serj115 120 12ΕΪ

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cacjSer Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln Hiss130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac tttSer Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phç145 150 155

qt

c

' Pi

gat tcco Asp Ser

OC

a

Tli

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgcSer Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cy^165 170

gta actr Val Thr

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tetSer Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Sei180 185 ' !

gcc ttc tgc acc gcg tat ccg. ctc ctc tgc aaa gac ccc'Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Prçj,195 200. 205

gç[t ctg accGJy Leu Thr160

aitc aag, aacTljir Lys Asn175

acc tgc gacTlir Cys Asp150

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac; t

Thr Leu Arg Gly Asn Phe Ala Ala. Pro Asn Gly Asp Tyr'210 215 220

ttc tgg cct tcc ctg gct gea tcc ggc aat ccc gac aab

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn225 230 235

AL

Ty

;t aac gtca Asn Val

ac act cagr Thr Gln

tgc ggg gag tgt ttc, gag gtc ate cgc. acc aag ccc gacCys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp245 250

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtlTyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile VaJl260 265

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgjcVal Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys275 280 285

ac ctc tetyr Leu Ser240

ggg aca gacGly Thr Asp255

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac ggPro Pro. Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gl,y290 295 300

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaaThr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Gly305 310 315

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atij:Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Mejt325 330

tc gag gtaeu Glu Val70 -

tgtC ys

aag cggLys Arg

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctAsp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Le340 345

caa aat ctcC-In Asn Leu

tc gac ttc|le Asp Phe320

gac ctc tcc^isp Leu Ser335

384

432

480

528

576

624

672

720

7 68

816

864

912

960

fcc gac ggta Asp Gly$50

1008

1056gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln. Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

kag ggc aag gga ccc att act gtg ect gtt tcg atg agg ctg acg gcg 134 4

íln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc tcg acc ccg age tcg acc ggc gag aac aac ggc ttc tac 1488

Gln Phe Thr Ser Thr Pro Ser Ser Thr Gly Glu Asn Asn Gly Phe Tyr485 490 495

tac tcc ttc tgg acc gac ggc ggt gga gac gtg acc tac acc aac gga 1536

Tyr Ser Phe Trp Thr Asp Gly Gly Gly Asp Val Thr Tyr Thr Asn Gly500 505 510

Jat gct ggt gcc tac act gtt gag tgg tcc aac gtg ggc aac ttt gtc 1584

Asp Ala Gly Ala Tyr Thr Val Glu Trp Ser Asn Val Gly Asn Phe Val515 520 525

ggt gga aag ggc tgg aac ccc gga agt gcg cag gac ate acc tac age 1632

Gly Gly Lys Gly Trp Asn Pro Gly Ser Ala Gln Asp Ile Thr Tyr Ser530 535 540

ggc acc ttc acc ect age ggc aac ggc tac ctc tcc gtc tat ggc tgg 1680

Gly Thr Phe Thr Pro Ser Gly Asn Gly Tyr Leu Ser Val Tyr Gly Trp545 550 555 560

acc act gac cct ctg ate gag tac tac ate gtc gag tet tac ggc gac 1728

Thr Thr Asp Pro Leu Ile Glu Tyr Tyr Ile Val Glu Ser Tyr Gly Asp565 570 575

tac aac ccc ggc agt gga ggc acg tác aag ggc acc gtc acc tcg gac 1776

Tyr Asn Pro Gly Ser Gly Gly Thr Tyr Lys Gly Thr Val Thr Ser Asp580 585 590

gga tcc gtt tac gat ate tac acg gct acc cgt acc aat gct gct tcc 1824Gly Ser Val Tyr Asp Ile Tyr Thr Ala Thr Arg Thr Asn Ala Ala Ser595 600 605

att cag gga acc gct acc ttc act cag tac tgg tcc gtt cgc cag aac 1872

Ile Gln Gly Thr Ala Thr Phe Thr Gln Tyr Trp Ser Val Arg Gln Asn610 615 620

aag aga gtt ggc gga acc gtt acc acc tcc aac cac ttc aat gct tgg 1920

Lys Arg Val Gly Gly Thr Val Thr Thr Ser Asn His Phe Asn Ala Trp625 630 635 640

gct aag ctg gga atg aac ctg ggt act cac aac tac cag ate gtg gct 1968

Ala Lys Leu Gly Met Asn Leu Gly Thr His Asn Tyr Gln Ile Val Ala.

645 650 655

acc gag ggt tac cag age agt gga tet tcg tcc ate act gtt cag 2013

Thr Glu Gly Tyr Gln Ser Ser Gly Ser Ser Ser Ile Thr Val Gln660 665 670

"210> 74<211> 671<212> PRT

<213> ( Seqüência artificial·"

<220>___

<223> Construção Sintética

<400> 74

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr15 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln Hisj Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe145 150 155

Gly Leu Thr160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cygi Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Se^ Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp 'Pr<É>: Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyiip Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Ash Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Var260 265

1 Leu Glu Val270

Val Asp Ser Cys . Pro Cys Asn Ala Asn Ser Lys Trp C^s Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe. Ser Pro Pro Ser Asn GTi290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 1 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr JPhe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val

385

390

395

400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His.;Àsp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp JVal Leu. Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg lLeu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys. Glu Gly Ala Ile Thr:,450 455 460

Ser Tyr Thr

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp (Leu Gly Val465 470 475 480

Gln Phe Thr Ser Thr Pro Ser Ser Thr Gly Glu Asn Asn -jGly Phe Tyr485 490 495

Tyr Ser Phe Trp Thr Asp Gly Gly Gly Asp Val Thr Tyr JiThr Asn Gly500 505 510

Asp Ala Gly Ala Tyr Thr Val Glu Trp Ser Asn Val Gly Asn Phe Val515 520 525

.Jly Gly Lys Gly Trp Asn Pro Gly Ser Ala Gln Asp Ilei Thr Tyr Ser

530

535

540

Gly Thr Phe Thr Pro Ser Gly Asn Gly Tyr Leu Ser Val

545

550

555

Tyr Gly Trp560

Thr Thr Asp Pro Leu Ile Glu Tyr Tyr. Ile Val Glu Ser iTyr Gly Asp565 '570 575

Tyr Asn Pro Gly Ser Gly Gly Thr Tyr Lys Gly Thr Val! Thr Ser Asp580 585 590

Gly Ser Val Tyr Asp Ile Tyr Thr Ala Thr Arg Thr AsnjjAla Ala Ser595 600 605

Ile Gln Gly Thr Ala Thr Phe Thr Gln Tyr Trp Ser Valjj Arg Gln Asn610

615

620

Lys Arg Val Gly Gly Thr Val Thr Thr Ser Asn His PhetAsn Ala Trp625 630 635 640

Ala Lys Leu Gly Met Asn Leu Gly Thr His Asn Tyr Glnil Ile Val Ala64 5 650 í 65.5

Thr Glu Gly Tyr Gln Ser Ser Gly Ser Ser Ser Ile Thr'Val Gln660 665 [670

<210> 75<211> 2151< 2 Γ2 >, * -DNA-..

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<400> 75

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt; att tet tatGln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr

10

15

acc ggg tet acc tgc tgt cag agt ggg aat acc.tgc gcç gag att aacThr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Aláf Glu Ile Asn20 25 30

48

96

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt*' act tca actSer Tyr Tyr Tyr.Gln Cys Ile Pro Ala Thr Ala Val Se^ Thr Ser Thr35 40 45

acc aca gtg aca tet ccc tet age tet.ggt. tcg tet tc|. gcc aac acgThr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Se$ Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccç agt ccc acsjSer Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Th^65 70 75

gea aca cagAla Thr Gln80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctcAsn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Sef Trp Ala Leu85 90 ! 95I.[

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gai aat gaa tccVal Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 ; 110

1.4 4

192

240

288

336

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc ag;t cct gat tccGlu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Sefc Pro Asp Ser115 120 12·β

384tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac §cc <?ta actSer Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt jggt ctg accSer Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe ifely Leu Thr145 150 155 160

432

480

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc ãcc aag aacSer Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys ;Thr Lys Asn165 170 175

528

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gacSer Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser ÍThr Cys Asp

180

185

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac cccAla Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr210 215 220

<190

gct aac ..gtcMa Asn Val

jtac. act cagiTyr Thr Gln

576

624

672

ttc tgg cct tcc ctg gct gea tcc ggc aat ccc gac aac jtac· ctc t.ctPhe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn225 230 235

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gacCys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp245 250

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc.jTyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Valj260 265

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgcjVal Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga!Pro Pro Pro.Pro Pro Phe Phe Ser Pro Pro Ser.Asn Glyj290 295 300

T.yr Leu Ser240

ggg aca gacGly Thr Aspf 255

ctc gag gtaLeu Glu Val270

tgt aag cggCys Lys Arg

caa aat ctcGln Asn Leu

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaaijl ate gac ttcThr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glujjlle Asp Phe305 310 315 320

720

768

816

864

912

960

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atgl gac ctc tccLys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His MetjAsp Leu Ser325 330 335

1008

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctcl gcc gac ggtAsp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leujj-Ala Asp Gly340 345 350

1056

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aagj' ccg ggg aacVal Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lysi Pro Gly Asn355 360 365

1104

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat;!; ttt gcg ctg

1152Ile Tyr Ile Trp Leu His Asp Gly Ala Gly. Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc etc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296

Tyr. Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly . Ser Trp Val Leu Pro'420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 1344

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

fro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc ggc tcg act tac tcc agt gga tet tet tcg ggg tcg ggg 1488

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

tet age tcc age tcg agt tcg act acc act aag gcc act tcg acg acc 1536

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

ttg aag act acc tcg acc acc age agt gga age agt tcg aca tcg gcg 1584

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

kgcg tcg acc ccg age tcg acc ggc gag aac aac ggc ttc tac tac tcc 1632

Ua Ser Thr Pro Ser Ser Thr Gly Glu Asn Asn Gly Phe Tyr Tyr Ser530 535 540

ttc tgg acc gac ggc ggt gga gac gtg acc tac acc aac gga gat gct 1680

Phe Trp Thr Asp Gly Gly Gly Asp Val Thr Tyr Thr Asn Gly Asp Ala545 550 555' 560

ggt gcc tac act gtt gag tgg tcc aac gtg ggc aac ttt gtc ggt gga 1728Gly Ala Tyr Thr Val Glu Trp Ser Asn Val Gly Asn Phe Val Gly Gly565 570 575

aag ggc tgg aac ccc gga agt gcg cag gac ate acc tac age ggc acc 1776Lys Gly Trp Asn Pro Gly Ser Ala Gln Asp Ile Thr Tyr Ser GIy Thr580 585 590

ttc acc cct age ggc aac ggc tac ctc tcc gtc tat ggc tgg acc act 1824

Phe Thr Pro Ser Gly Asn Gly Tyr Leu Ser Val Tyr Gly Trp Thr Thr595 600 605

gac cct ctg ate gag tac tac ate gtc gag tet tac ggc gac tac aac 1872Asp Pro Leu Ile Glu Tyr Tyr Ile Val Glu Ser Tyr Gly Asp Tyr Asn610 615 620

ccc ggc agt gga ggc acg tac aag ggc acc gtc acc tcg gac gga tccPro Gly Ser Gly Gly Thr Tyr Lys Gly Thr Val Thr Ser Asp Gly Ser625 630 635 640

gtt tac gat ate tac acg gct acc cgt acc aat gct gct tcc att cagVal Tyr Asp Ile Tyr Thr Ala Thr Arg Thr Asn Ala Ala Ser Ile Gln645 650 655

gga acc gct acc ttc act cag tac tgg tcc gtt cgc cag aac aag agaGly Thr Ala Thr Phe Thr Gln Tyr Trp Ser Val Arg Gln Asn Lys Arg660 665 670

gtt ggc gga acc gtt acc acc tcc aac cac ttc aat gct tgg gct aagVal Gly Gly Thr Val Thr Thr Ser Asn His Phe Asn Ala Trp Ala Lys675 680 685

ctg gga atg aac ctg ggt act cac aac tac cag ate gtg gct acc gagLeu Gly Met Asn Leu Gly Thr His Asn Tyr Gln Ile Val Ala Thr Glu690 695 700

gt tac cag age agt gga tet tcg tcc ate act gtt cagGly Tyr Gln Ser Ser Gly Ser Ser Ser Ile Thr Val Gln705 710 715

<210> 76<2,1.1 > 717

<213> Seqüência· artificial

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<400> 7 6

Gln Ser Ser Cvs Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

|r Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala.Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met LeU Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

[Some texts missing on original document] Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Aspi Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

yr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly

485 490

er Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 490 495

Leu Lys Thr Thr Ser Thr Thr. Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

Ala Ser Thr Pro Ser Ser Thr Gly Glu Asn Asn Gly Phe Tyr Tyr Ser530 535 540

Phe Trp Thr Asp Gly Gly Gly Asp Val Thr Tyr Thr Asn Gly Asp Ala545 550 555 560

Gly Ala Tyr Thr Val Glu Trp Ser Asn Val Gly Asn Phe Val Gly Gly565 570 575

Lys Gly Trp Asn Pro Gly Ser Ala Gln Asp Ile Thr Tyr Ser Gly Thr580 585 590Phe Thr Pro Ser Gly Asn Gly Tyr Leu Ser Val Tyr Gly Trp Thr Thr595 600 605

Asp Pro Leu Ile Glu Tyr Tyr Ile Val Glu Ser Tyr Gly Asp Tyr Asn610 615 620

Pro Gly Ser Gly Gly Thr Tyr Lys Gly Thr Val Thr Ser Asp Gly Ser625 630 635 640

Val Tyr Asp Ile Tyr Thr Ala Thr Arg Thr Asn Ala Ala Ser Ile Gln645 650 655

Gly Thr-Ala Thr Phe Thr Gln Tyr Trp Ser Val Arg Gln Asn Lys Arg660 665 670

Val Gly Gly Thr Val Thr Thr Ser Asn His Phe Asn Ala Trp Ala Lys675 680 685

Leu Gly Met Asn Leu Gly Thr His Asn Tyr Gln Ile Val Ala Thr Glu690 695 700

Gly Tyr Gln Ser Ser Gly Ser Ser Ser Ile Thr Val Gln705 710 715

<210> 77

<213> SeqúêncLa"artificiái'?

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3 > Proteína de fusão::

<220>

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<4 00> 77

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat 48

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr15- 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac . 96

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys-Ala Glu Ile Asn20 25 30

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca act 144

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acg 192Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gca aca cag 240Ser Gly tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctc 288Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu55 90 95

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

|cc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 432Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 480Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 576Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gca tcc ggc aat ccc gac aac tac ctc tet 720Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 864Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctcPro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu912290 295 300

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn ThrAsn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 12 96

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc -att act gtg cct gtt tcg atg agg ctg acg gcg' 1344Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

ro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 '470 475 480

cag ttc acc cag tcg gcc tgc act ctc caa tcg gag act cac ccg cct 1488

Gln Phe Thr Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro485 490 495

ctg aca tgg cag aaa tgc tcg tet ggt ggc acg tgc act caa cag aca 1536

Leu Thr Trp Gln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr500 505 510

ggc tcc gtg gtc ate gac gcc aac tgg cgc tgg act cac gct acg aac 1584

Gly Ser Val Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn515 520 525

age age acg aac tgc tac gat ggc aac act tgg age tcg acc cta tgtSer Ser Thr Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys530 535 540cct gac aac gag acc tgc gcg aag aac tgc tgt ctg gac ggt gcc gcc 1680

Pro Asp Asn Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala545 550 555 560

tac gcg tcc acg tac gga gtt acc acg age ggt aac age ctc tcc att 1728

Tyr Ala Ser Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile565 570 . 575

ggc ttt gtc acc cag tet gcg cag aag aac gtt ggc gct cgc ctt tac 177 6Gly Phe Val Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr580 585 590

ctt atg gcg age gac acg acc tac cag gaa ttc acc ctg ctt ggc aac 1824

Leu Met Ala Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn595 600 605

gag ttc tet ttc gat gtt gat gtt tcg cag ctg ccg tgc ggc ttg aac 1872Glu Phe Ser Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn '610 . 615 620

Pga gct ctc tac ttc gtg tcc atg gac gcg gat ggt ggc gtg age aag 1920

Gly Ala Leu Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys625 630 : 635 640

tat ccc acc aac acc gct ggc gcc aag tac ggc acg ggg tac tgt gac 1968

Tyr Pro Thr Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp645 650 655

age cag tgt ccc cgc gat ctg aag ttc ate aat ggc cag gcc aac gtt 2016

Ser Gln Cys Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val660 665 670

gag ggc tgg gag ccg tca tcc aac aac gcg aac acg ggc att gga gga 2064

Glu Gly Trp Glu Pro-Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly675 680 685

cac gga age tgc tgc tet gag atg gat ate tgg gag gcc aac tcc ate 2112

His Gly Ser Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile690 695 700

xc gag gct ctt acc ccc cac cct tgc acg act gtc ggc cag gag ate 2160

Ser Glu Ala .Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile705 710 715 ' 720

tgc gag ggt gat ggg tgc ggc gga act tac tcc gat aac aga tat ggc 2208

Cys Glu Gly Asp Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly725 730 735

ggc act tgc gat ccc gat ggc tgc gac tgg aac cca tac cgc ctg ggc 2256

Gly Thr Cys Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr. Arg Leu Gly740 745 750

aac acc age ttc tac ggc cct ggc tca age ttt acc ctc gat acc acc 2304

Asn Thr Ser Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu Asp Thr Thr755 760 765

aag aaa ttg acc gtt gtc acc cag ttc gag acg tcg ggt gcc ate aac 2352

Lys Lys Leu Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn770 775 · 780cga tac tat gtc cag aat ggc gtc act ttc cag cag ccc aac gcc gagArg Tyr Tyr Val Gln Asn Gly Val Thr Phe Glri Gln Pro Asn Ala Glu785 790 795 800

2400

ctt ggt agt tac tct ggc aac gag ctc aac gat gat tac tgc aca gct 2448

Leu Gly Ser Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ála805 810 815

gag gag gca gaa ttc ggc gga tcc tct ttc tca gac aag ggc ggc ctg 2496

Glu Glu Ala Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu820 825 830

act cag ttc aag aag gct acc tct ggc ggc atg gtt ctg gtc atg agt 254 4

Thr Gln Phe Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser835 840 845

ctg tgg gat gat tac tac gcc aac atg ctg tgg ctg gac tcc acc tac 2592

Leu Trp Asp Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr850 855 860

cg aca aac gag acc tcc tcc aca ccc ggt gcc gtg cgc gga age tgc 2640Pro Thr Asn Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys .865 870 875 880

tcc acc age tcc ggt gtc cct gct cag gtc gaa tct cag tct ccc aac 2688

Ser Thr Ser Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn885 890 895

gcc aag gtc acc ttc tcc aac ate aag. ttc gga ccc att ggc age acc 2736

Ala Lys Val Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr900 905 910

ggc aac cct age ggc ggc aac cct ccc ggc gga aac ccg cct ggc acc 2784

Gly Asn Pro Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr915 920 925

acc acc acc cgc cgc cca gcc act acc act gga age tct ccc gga cct 2832

Thr Thr Thr Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro930 935 940

acc cag tct cac tac ggc cag tgc ggc ggt att ggc tac age ggc ccc 2880

Thr Gln Ser His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro945 950 955 960

acg gtc tgc gcc age ggc aca act tgc cag gtc ctg aac cct tac tac 2928

Thr Val Cys Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr965 970 975

tct cag tgc ctg taa 2943

Ser Gln Cys Leu980

<210> 78

<211> 980

<212> PRT

<213> Seqüência artificial

<220><223>

Construção Sintética<400> 78

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr- Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

rs Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 - 375 -380

Ser Ala Val Asn Thr Asn Gly Pro. Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

?ln Ala Gly Gly Ser Gly. Pro Trp VarI Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gl-y Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 . 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 ' 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480Gln Phe Thr Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro485 490 495

Leu Thr Trp Gln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr500 505 510

Gly Ser Vàl Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn515 520 525

Ser Ser Thr Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys530 535 540

Pro Asp Asn Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala545 550 555 560

^Tyr Ala Ser Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile565 570 575

Gly Phe Val Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr580 585 590

Leu Met Ala Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn595 600 605

Glu Phe Ser Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn610 615 620

Gly Ala Leu Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys625 630 635 640

^Tyr Pro Thr Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp645 650 655

Ser Gln Cys Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val660 665 670

Glu Gly Trp Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly675 680 685

His Gly Ser Cys Cys Ser Glu Met Asp Ile Trp GlU Ala Asn Ser Ile690 695 700

Ser Glu Ala Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile705 710 715 720725 730 735

Gly Thr Cys Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly740 745 750

Asn Thr Ser Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu Asp Thr Thr755 760 765

Lys Lys Leu Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn770 775 780

Arg Tyr Tyr Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu785 790 795 800

Leu Gly Ser Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala805 810 815

Glu Glu Ala Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu820 825 830

Thr Gln Phe Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met. Ser835 840 845

Leu Trp Asp Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr850 855 860

Pro Thr Asn Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys865 870 875 880

Ser Thr Ser Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn885 890 895

Ala Lys Val Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr900 905 910

Gly Asn Pro Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr915 920 925

Thr Thr Thr Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro930 935 940

Thr Gln Ser His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro945 950 955 960

Thr Val Cys Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr965 970 975Ser Gln Cys Leu980

<210> 79<211> 3081

<212> DNA

<213> Seqüência; artificial

<220>

<223> rProtema'deifusã'o

<220>

<221> CDS

<222> (1)..(3081)

<400> 79

ag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat

ln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 . 10 15

48

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aacThr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

96

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca actSer Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

144

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acgThr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

192

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cagSer Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

ac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctcAsn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

240

288

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tccVal Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

336

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tccGlu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

384

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta actSer Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr'130 135 140

432

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg accSer Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

480

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac

528Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 576

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Âsn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gea tcc ggc aat ccc gac aac tac ctc tet 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768

rs Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 8 64

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

ag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

ys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu .370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aacGln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn

1248405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 134 4

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc ggc tcg act tac tcc agt gga tet tet tcg ggg tcg ggg 1488

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 .490 495

tet age tcc age tcg agt tcg act acc act aag gcc act tcg acg acc 1536Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

ttg aag act acc tcg acc acc age agt gga age agt tcg aca tcg gcg 1584Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 . 525

gcg cag tcg gcc tgc act ctc caa tcg gag act cac ccg. cct ctg aca 1632

Ala Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro Leu Thr530 535 540

tgg cag aaa tgc tcg tet ggt ggc acg tgc act caa cag aca ggc tcc 1680

Trp Gln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser545 550 555 560

gtg gtc ate gac gcc aac tgg cgc tgg act cac gct acg aac age age 1728Val Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn Ser Ser565 570 575

acg aac tgc tac gat ggc aac act tgg age tcg acc ctatgt cct gac 1776

Thr Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp580 585 590

aac gag acc tgc gcg aag aac tgc tgt ctg gac ggt gcc gcc tac gcg 1824

Asn Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala595 600 605

tcc acg tac gga gtt acc acg age ggt aac age ctc tcc att ggc ttt 1872

Ser Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser. Ile Gly Phe610 615 620

gtc acc cag tet gcg cag.aag aac gtt ggc gct cgc ctt tac ctt atg 1920

Val Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr Leu Met625 630 635 640

gcg age gac acg acc tac cag gaa ttc acc ctg ctt ggc aac gag ttc 1968

Ala Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe645 650 655tct ttc gat gtt gat gtt tcg cag ctg ccg tgc ggc ttg aac gga gct 2016

Ser Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala660 665 670

ctc tac ttc gtg tcc atg gac gcg gat ggt ggc gtg age aag tat ccc 2064

Leu Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro675 680 685

acc aac acc gct ggc gcc aag tac ggc acg ggg tac tgt gac age cag 2112

Thr Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln690 695 700

tgt ccc cgc gat ctg aag ttc ate aat ggc cag gcc aac gtt gag ggc 2160

Cys Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val Glu Gly705 710 715 720

tgg gag ccg tca tcc aac aac gcg aac acg ggc att gga gga cac gga 2208

Trp Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly His Gly725 730 735

c tgc tgc tct gag atg gat ate tgg gag gcc aac tcc ate tcc gag 225.6er Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu740 745 750

gct ctt "acc ccc cac cct tgc acg act gtc ggc cag gag ate tgc gag 2304

Ala Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile Cys Glu755 760 .765

ggt gat ggg tgc ggc gga act tac tcc gat aac aga tat ggc ggc act 2352

Gly Asp Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr770 775 780

tgc gat ccc gat ggc tgc gac tgg aac cca tac cgc ctg ggc aac acc 2400

Cys Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr785 ' 790 795 800

age ttc tac ggc cct ggc tca age ttt acc ctc gat acc acc aag aaa 2448

Ser Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys805 810 815

Itg acc gtt gtc acc cag ttc gag acg tcg ggt gcc ate aac cga tac 24 96

Leu Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr820 825 830

tat gtc cag aat ggc gtc act ttc cag cag ccc aac gcc gag ctt ggt 254 4

Tyr Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly835 840 845

agt tac tct ggc aac gag ctc aac gat gat tac tgc aca gct gag gag 2592

Ser Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu850 855 860

gea gaa ttc ggc gga tcc tct ttc tca gac aag ggc ggc ctg act cag 2640

Ala Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln865 870 875 880

ttc aag aag gct acc tct ggc- ggc atg gtt ctg gtc atg agt ctg tggPhe Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser Leu Trp885 890 895

2688gat gat tac tac gcc aac atg ctg tgg ctg gac tcc acc tac ccg acaAsp Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr900 905 910

2736

aac gag acc tcc tcc aca ccc ggt gcc gtg cgc gga age tgc tcc accAsn Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys Ser Thr91-5 920 925

2784

age tcc ggt gtc cct gct cag gtc gaa tet cag tet ccc aac gcc aagSer Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn Ala Lys930 935 940

2832

gtc acc ttc tcc aac ate aag ttc gga ccc att ggc age acc ggc aacVal Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn945 950 955 960

2880

cct age ggc ggc aac cct ccc ggc gga aac ccg cct ggc acc acc accPro Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr Thr Thr965 970 975

2928

kcc cgc cgc cca gcc act acc act gga age tet ccc gga cct acc cagThr Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro Thr Gln980 985 990

2976

tet cac tac ggc cag tgc ggc ggt att ggc tac age ggc ccc acg gtcSer His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val995 1000 1005

3024

tgc gcc age ggc aca act tgc cag gtc ctg aac cct tac tac tetCys Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr Ser1010 1015 1020

3069

cag tgc ctg taaGln Cys Leu1025

3081

<210> 80<211> 1026s< 212><7BRT

213> Seqüência artificial

<220>

<223> Construção Sintética

<400> 80

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 HO

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Mét Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 . 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

5er Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

pPro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser. Thr Ser Ala515 520 525

Ala Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro Leu Thr530 535 540Trp Gln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser545 550 555 560

Val Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn Ser Ser565 570 575

Thr Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp580 585 590

Asn Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala595 600 605

Ser Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe610 615 620

Sal Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr Leu Met25 630 635 640

Ala Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe645 650 655

Ser Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala660 665 670

Leu Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro675 680 685

Thr Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln690 695 700

F:ys Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val Glu Gly705 710 715 720

Trp Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly His Gly725 730 735

Ser Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu740 745 750

Ala Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile Cys Glu755 760 765

Gly Asp Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr770 775 780

Cys Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr785 790 795 800

Ser Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys805 810 815

Leu Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr820 825 830

Tyr Val Gln Asn Gly Val Thr.. Phe Gln Gln Pro Asn Ala Glu Leu Gly835 840 845

Ser Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu850 855 860

Ala Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln865 870 875 880

Phe Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser Leu Trp885 890 895

Asp Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr900 905 910

Asn Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys Ser Thr915 920 925

Ser Ser Gly Val Pro Ala Gln Val Glu Ser. Gln Ser Pro Asn Ala Lys930 935 940

,Val Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn345 950 955 960

Pro Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr Thr Thr965 970 975

Thr Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro Thr Gln980 985 990

Ser His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val995 1000 1005

Cys Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr Ser1010 1015 1020

Gln Cys Leu1025<210> 81

<211> 2943

<212> DNA

<213> "Seqüência artificial

<220><22 3>

Efoteina defusãb

<220>

<221> CDS<222> .(1) - · (2943)

<400> 81

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att-tct tatGln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

48

icc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aactar Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

96

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca actSer Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 .40 45

144

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acgThr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

192

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cagSer Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

240

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct etcAsn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 .95

288

jtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tccfal Asp Asn Val Cys Cys Pro Tyr Tyr. Cys Leu Ser Asp Asn Glu Ser100 105 110

336

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tccGlu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

384

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta actSer Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 " 135 140

432

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg accSer Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

480

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aacSer Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

528

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 57 6Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 . 205

act ctc cgc ggg aac.ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gca tcc ggc aat ccc gac aac tac ctc tct 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

{τ Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val"" 2 60 '·■""' 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 8 64

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc. ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gca gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

jp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 ■ 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tct tgg gtc ctc ccgTyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro

1296420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 1344

Gln Gly Lys Gly Pro Ile Thr'Val Pro Val Ser Het Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 14 40

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc cag tcg gcc tgc act ctc caa tcg gag act cac ccg cct 14 88

Gln Phe Thr Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro485 490 495

ctg aca tgg cag aaa tgc tcg tet ggt ggc acg tgc act caa cag aca 1536

ju Thr Trp Gln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr500 505 510

ggc tcc gtg gtc ate gac gcc aac tgg cgc tgg act cac-gct acg aac 1584

Gly Ser Val Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn515 520 525

age age acg aac tgc tac gat ggc aac act tgg age tcg acc cta tgt 1632

Ser Ser Thr Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys530 535 540

cct gac aac gag acc tgc gcg aag aac tgc tgt ctg gac ggt gcc gcc 1680

Pro Asp Asn Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala545 550 555 560

tac gcg tcc acg tac' gga gtt acc acg age ggt aac age ctc tcc att 1728

Tyr Ala Ser Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile565 570 575

gc ttt gtc acc cag tet gcg cag aag aac gtt ggc gct cgc ctt tac 1776.

Iy Phe Val Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr580 585 590

ctt atg gcg age gac acg acc tac cag gaa ttc acc ctg ctt ggc aac 1824

Leu Met Ala Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn595 600 605·

gag ttc tet ttc gat gtt gat gtt tcg cag ctg ccg tgc ggc ttg aac 1872

Glu Phe Ser Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn610 615 620

gga gct ctc tac ttc gtg tcc atg gac gcg gat ggt ggc gtg age aag 1920

Gly Ala Leu Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys625 630 635 640

tat ccc acc aac acc gct ggc gcc aag tac ggc acg ggg tac tgt-gac 1968

Tyr Pro Thr Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp645 650 655

age cag tgt ccc cgc gat ctg aag ttc ate aat ggc cag gcc aac gttSer Gln Cys Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val660 665 670

2016gag ggc tgg gag ccg tca tcc aac aac gcg aac acg ggc att gga gga 2064

Glu Gly Trp Glu Pro Ser Ser Asn Asn. Ala Asn Thr Gly Ile Gly Gly675 680 685

cac gga age tgc tgc tet gag atg gat ate tgg gag gcc aac tcc ate 2112

His Gly Ser Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile 690 695 700

tcc gag gct ctt acc ccc cac cct tgc acg act gtc ggc cag gag ate 2160

Ser Glu Ala Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile705 710 715 720

tgc gag ggt gat ggg tgc ggc gga act tac tcc gat aac aga tat ggc 2208

Cys Glu Gly Asp Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly725 730 735

ggc act tgc gat ccc gat ggc tgc gac tgg aac cca tac cgc ctg ggc 2256

Gly Thr Cys Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly740 745 750

ac acc age ttc tac ggc cct ggc tca age ttt acc etc gat acc acc 2304

Asn Thr Ser Phe Tyr Gly Pro Gly Ser. Ser Phe Thr Leu Asp Thr Thr755 760 765

aag aaa ttg acc gtt gtc acc cag ttc gag acg tcg ggt gcc ate aac 2352

Lys Lys Leu Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn770 775 780

cga tac tat gtc cag aat ggc gtc act ttc cag cag ccc aac gcc gag 2400

Arg Tyr Tyr Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu785 790 795 800

ctt ggt agt tac tet ggc aac gag ctc aac gat gat tac tgc aca gct 24 48

Leu Gly Ser Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala805 810 815

gag gag gea gaa ttc ggc gga tcc tet ttc tca gac aag ggc ggc ctg 2496

Glu Glu Ala Glu Phe Gly Gly Ser· Ser Phe Ser Asp Lys Gly Gly Leu820 825 830

act cag ttc aag aag gct acc tet ggc ggc atg gtt ctg gtc atg agt 2544

Thr Gln- Phe Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser835 840 845

ctg tgg gat gat tac tac gcc aac atg ctg tgg ctg gac tcc acc tac 2592

Leu Trp Asp Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr850 855 860

ccg aca aac gag acc tcc tcc aca ccc ggt gcc gtg cgc gga age tgc 2640

Pro Thr Asn Glu. Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys865 870 875 880

tcc acc age tcc ggt gtc cct gct cag gtc gaa.tet cag tet ccc aac 2688

Ser Thr Ser Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn885 890 895

gcc aag gtc acc ttc tcc aac ate aag ttc gga ccc att ggc age acc 2736

Ala Lys Val Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr900 905 910ggc aac cct age ggc ggc aac cct ccc ggc gga aac ccg cct ggc accGly Asn Pro Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr915 920 925

acc acc acc cgc cgc cca gcc act acc act gga age tet ccc gga cctThr Thr Thr Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro930 935 940

acc cag tet cac tac ggc cag tgc ggc ggt att ggc tac age ggc cccThr Gln Ser His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro945 950 955 960

acg gtc tgc gcc age ggc aca act tgc cag gtc ctg aac cct tac tacThr Val Cys Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr965 970 975

tet cag tgc ctg taaSer Gln Cys Leu980

<210> 82

<211> 980

<212> -PRT-

<213> Seqüência artfficial

<220>

<223> Construção Sintética

<400> 82

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Vál Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu'Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu'Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg. Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val435 440

Pro Asn Gly Gln Gln Val Val Lys450 455

Pro Pro Ala Thr Ala Val Glu Gly465 470

Pro Val Ser Met Arg Leu Thr Ala445

Glu Gly Ala Ile Thr Ser Tyr Thr460

Phe Trp Tyr Ile Asp Leu Gly Val475 480

Gln Phe Thr Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro485 490 495

Leu Thr Trp Gln Lys Cys Ser.Ser Gly Gly Thr Cys Thr Gln Gln Thr500 505 510

Gly Ser Val Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn515 520 525

Ser Ser Thr Asn Cys Tyr Asp Gly Asn Thr Trp Ser. Ser Thr Leu Cys530 535 540

Pro Asp Asn Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala545 550 555 560

Tyr Ala Ser Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile565 570 575

Gly Phe Val Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr580 585 590

Leu Met Ala Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn595 600 605Glu Phe Ser Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn610 615 620

Gly Ala Leu Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys625 630 635 640

Tyr Pro Thr Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp645 650 655.

Ser Gln Cys Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val660 665 670

Glu Gly Trp Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly675 680 685

-s Gly Ser Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile. 690 695 ' 700

Ser Glu Ala Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile705 710 715 720

Cys Glu Gly Asp Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly725 730 735

Gly Thr Cys Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly740 745 750

Asn Thr Ser Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu. Asp Thr Thr755 760 765

*

s Lys Leu Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn770 775 780

Arg Tyr Tyr Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu785 790 795 800

Leu Gly Ser Tyr Ser Gly Asn Glu.Leu Asn Asp Asp Tyr Cys Thr Ala805 810 815

Glu Glu Ala Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu820 825 830

Thr Gln Phe Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser8 35 840 '845

Leu Trp Asp Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr850 855 850

Pro Thr Asn Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys865 870 875 880

Ser Thr Ser Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn885 890 895

Ala Lys Val Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr900 905 910

Gly Asn Pro Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr915 320 925

Thr Thr Thr Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro930 935 94,0

Thr Gln Ser His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro945 950 955 960

Thr Val Cys Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr965 970 975

Ser Gln Cys Leu980

<210> 83

<211> 3081 .

<212> DNA

<213> Seqüência artificial

<220>

<223> Proteina de fusao

<220>

<221> CDS

<222> (1)..(3081)

<400> 83

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile' Ser Tyr

1 5 10 15

48

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aacThr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

96

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca actSer Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

144acc aca gtg aca tct ccc tct age tct ggt tcg tet tet gcc aac acg - 192Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 -60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cag 240

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctc 288

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 38 4

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

^tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 4 32

"ser Met Cys Lys Ser Gly Thr Met .Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 480

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tct acc tgc gac 57 6

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

ict ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gea tcc ggc aat ccc gac aac tac ctc tct . 720Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac ■ 7 68

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val'260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 864

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc

912Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152Jle Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate .gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 1344

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

ro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val.465 470 475 480

cag ttc acc ggc tcg act tac tcc agt gga tet tet tcg ggg tcg ggg 1488

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

tet age tcc age tcg agt tcg act acc act aag gcc act tcg acg acc 1536

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

ttg aag act acc tcg acc acc age agt gga age agt tcg aca tcg gcg 1584

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

gcg cag tcg gcc tgc act ctc caa tcg gag act cac ccg cct ctg aca 1632

Ala Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro Leu Thr530 535 540

tgg cag aaa tgc tcg tct ggt ggc acg tgc act caa cag aca ggc tcc 1680

Trp Gln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser545 550 555 560

gtg gtc ate gac gcc aac tgg cgc tgg act cac gct acg aac age age 1728

Val Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn Ser Ser565 570 575

acg aac tgc tac gat ggc aac act tgg age tcg acc cta tgt cct gac 177 6

Thr Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp580 585 590

aac gag acc tgc gcg aag aac tgc tgt ctg gac ggt gcc gcc tac gcg 1824

Asn Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala595 600 605

tcc acg tac gga gtt acc acg age ggt aac age etc tcc att ggc ttt 1872

Ser Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe610 615 620

gtc acc cag tct gcg cag aag aac gtt ggc gct cgc ctt tac ctt atg 1920

Val Thr Gln Ser Ala Gln Lys Asn Val Gly Ala Arg Leu Tyr Leu Met625 630 635 640

gcg age gac acg acc tac cag gaa ttc acc ctg ctt ggc aac gag ttc 1968

Ala Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu Gly Asn Glu Phe645 650 655

tct ttc gat gtt gat gtt tcg cag ctg ccg tgc ggc ttg aac gga gct 2016

Ser Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala660 665 670

ctc tac ttc gtg tcc atg gac gcg gat ggt ggc gtg age aag tat ccc 2064

Leu Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro675 680 685

acc aac acc gct ggc gcc aag tac ggc acg ggg tac tgt gac age cag 2112

Thr Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln690 695 700

tgt ccc cgc gat ctg aag ttc ate aat ggc cag gcc aac gtt gag ggc 2160

Cys Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val Glu Gly705 710 715 720

tgg gag ccg tca tcc aac aac gcg aac acg ggc att gga gga cac gga 2208

Trp Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly His Gly725 730 735

age tgc tgc tct gag atg gat ate tgg gag gcc aac tcc ate tcc gag 2256

Ser Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu740 745 750

gct ctt acc ccc cac cct tgc acg act gtc ggc cag gag ate tgc gag 2304

Ala Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile Cys Glu755 760 765

ggt gat ggg tgc ggc gga act tac tcc gat aac aga tat ggc ggc act 2352

Gly Asp Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr770 775 780tgc gat ccc gat ggc tgc gac tgg aac cca tac cgc ctg ggc aac acc 2400

Cys Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr785 790 795 800

age ttc tac ggc cct ggc tca age ttt acc ctc gat acc acc aag aaa 24 48

Ser Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys805 810 815

ttg acc gtt gtc acc cag ttc gag acg tcg ggt gcc ate aac cga tac 2496

Leu Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr '820 825 830

tat gtc cag aat ggc gtc act ttc cag cag ccc aac gcc gag ctt ggt 2544

Tyr Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly835 840 845

agt tac tet ggc aac gag ctc aac gat gat tac tgc aca gct gag gag 2592

Ser Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu850 855 860

:a gaa ttc ggc gga tcc tet ttc tca gac aag ggc ggc ctg act cag 2640

Ala Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln865 870 875 880

ttc aag aag gct acc tet ggc ggc atg gtt ctg gtc atg agt ctg tgg 2688

Phe Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser Leu Trp885 890 895

gat gat tac tac gcc aac atg ctg tgg ctg gac tcc acc tac ccg aca 2736

Asp Asp Tyr Tyr Ala Asn. Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr ·900 905· 910

aac gag acc tcc tcc aca ccc ggt gcc gtg cgc gga age tgc tcc acc 2784

Asn Glu Thr Ser Ser, Thr Pro Gly Ala Val Arg Gly Ser Cys Ser Thr915 920 925

age tcc ggt gtc cct gct cag gtc gaa tet cag tet ccc aac gcc aag 2832

Ser Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn Ala Lys930 935 940

tc acc ttc tcc aac ate aag ttc gga ccc att ggc age acc ggc aac 2880

Val Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn945 950 955 960

cct age ggc ggc aac cct ccc ggc gga aac ccg cct ggc acc acc acc 2928

Pro §er Gly Gly Asn Pro Pro Gly Gly Asn Pro. Pro Gly Thr Thr Thr965 970 975

acc cgc cgc cca gcc act acc act gga age tet ccc gga cct acc cag 2976

Thr Arg Arg Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro Thr Gln980 985 990

tet cac tac ggc cag tgc ggc ggt att ggc tac age ggc ccc acg gtc 3024Ser His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val995 1000 1005

tgc gcc age ggc aca act tgc cag gtc ctg aac cct tac tac tetCys Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro. Tyr Tyr Ser1010 1015 1020

3069cag tgc ctg taaGln Cys Leu1025

<210> 84

<211> 1026

<212> PRT

<213> SéqUência artificial

<220>

<223> Construção Sintética

<400>

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr15 10 15

Dhr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala' Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 '90 95

IVal Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn.Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr115 120

Ser Met Cys Lys Ser Gly Thr Met130 135

Ser Asn Glu Asp Trp His Tyr Ser145 150

Gly Gly Cys Gly Ser Pro Asp Ser125

Trp Gly Glu Gln His Thr Val Thr140

Arg Ser Thr His Phe Gly Leu Thr155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190Ala Phe Cys Thr Ala Tyr Pro Leu Leu .Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro .Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro ,Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu . Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430Gln Gly Lys Gly Pro Ile Thr Val435 440

Pro Asn Gly Gln Gln Val Val Lys450 455

Pro Pro Ala Thr Ala Val Glu Gly465 470

Pro Val Ser Met Arg Leu Thr Ala445

Glu Gly Ala Ile Thr Ser Tyr Thr460 ·

Phe Trp Tyr Ile Asp Leu Gly Val475 480

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

Ala Gln Ser Ala Cys Thr Leu Gln Ser Glu Thr His Pro Pro Leu Thr530 535 540

Trp Gln Lys Cys Ser Ser Gly Gly Thr Cys Thr Gln Gln Thr Gly Ser545 550 555 560

Val Val Ile Asp Ala Asn Trp Arg Trp Thr His Ala Thr Asn Ser Ser565 570 575

Thr Asn Cys Tyr Asp Gly Asn Thr Trp Ser Ser Thr Leu Cys Pro Asp580 585 590

Fn Glu Thr Cys Ala Lys Asn Cys Cys Leu Asp Gly Ala Ala Tyr Ala595 600 605

Ser Thr Tyr Gly Val Thr Thr Ser Gly Asn Ser Leu Ser Ile Gly Phe610 615 620

Val Thr Gln Ser Ala Gln Lys Asn. Val Gly Ala Arg Leu Tyr Leu Met625 630 635 640

Ala Ser Asp Thr Thr Tyr Gln Glu Phe Thr Leu Leu- Gly Asn Glu Phe645 650 655

Ser Phe Asp Val Asp Val Ser Gln Leu Pro Cys Gly Leu Asn Gly Ala660 665 670Leu Tyr Phe Val Ser Met Asp Ala Asp Gly Gly Val Ser Lys Tyr Pro675 680 685

Thr Asn Thr Ala Gly Ala Lys Tyr Gly Thr Gly Tyr Cys Asp Ser Gln690 695 700

Cys Pro Arg Asp Leu Lys Phe Ile Asn Gly Gln Ala Asn Val Glu Gly705 710 715 720

Trp Glu Pro Ser Ser Asn Asn Ala Asn Thr Gly Ile Gly Gly His Gly725 730 735

Ser Cys Cys Ser Glu Met Asp Ile Trp Glu Ala Asn Ser Ile Ser Glu740 745 750

fa Leu Thr Pro His Pro Cys Thr Thr Val Gly Gln Glu Ile Cys Glu755 760 765

Gly Asp Gly Cys Gly Gly Thr Tyr Ser Asp Asn Arg Tyr Gly Gly Thr770 775 780

Cys Asp Pro Asp Gly Cys Asp Trp Asn Pro Tyr Arg Leu Gly Asn Thr785 790 795 800

Ser Phe Tyr Gly Pro Gly Ser Ser Phe Thr Leu Asp Thr Thr Lys Lys805 810 815

Leu Thr Val Val Thr Gln Phe Glu Thr Ser Gly Ala Ile Asn Arg Tyr820 825 830

)t Val Gln Asn Gly Val Thr Phe Gln Gln Pro Asn Ala Glu Leu Gly835 840 845

Ser Tyr Ser Gly Asn Glu Leu Asn Asp Asp Tyr Cys Thr Ala Glu Glu850 855 860

Ala Glu Phe Gly Gly Ser Ser Phe Ser Asp Lys Gly Gly Leu Thr Gln865 870 875 880

Phe Lys Lys Ala Thr Ser Gly Gly Met Val Leu Val Met Ser Leu Trp885 890 895

Asp Asp Tyr Tyr Ala Asn Met Leu Trp Leu Asp Ser Thr Tyr Pro Thr900 905 910

Asn Glu Thr Ser Ser Thr Pro Gly Ala Val Arg Gly Ser Cys Ser Thr915

920

925

Ser Ser Gly Val Pro Ala Gln Val Glu Ser Gln Ser Pro Asn Ala Lys930 935 940

Val Thr Phe Ser Asn Ile Lys Phe Gly Pro Ile Gly Ser Thr Gly Asn945 950 955 960

Pro Ser Gly Gly Asn Pro Pro Gly Gly Asn Pro Pro Gly Thr Thr Thr965 970 975

Thr Arg Arg Pro Ala Thr Thr. Thr Gly Ser Ser Pro Gly Pro Thr Gln980 985 990

er His Tyr Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val995 1000 1005

Cys Ala Ser Gly Thr Thr Cys Gln Val Leu Asn Pro Tyr Tyr Ser1010 1015 1020

Gln Cys Leu1025

<210> 85 <211 > 2793<6212 > DNA

<213> Seqüência ârtificiál

<220>

<22 3 > Proteína de fusão

220><221> CDS<222> (1)(2793)

<4 00> 85

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat 48

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac 96

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca act 144

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acg 192

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn- Thr50 55 60tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gca aca cag - 240

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 . 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctc 288

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336

Val Asp Asn Val Cys. Cys.Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 432

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

:cc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 480

rSer Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 576

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

fttc tgg cct tcc ctg gct gca tcc ggc aat ccc gac aac tac ctc tet 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

Tyr Ala Val Gly Glu. Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 864

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gca gac cac tgc ggc gaa ate gac ttc

960Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly' Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 . 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr' Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Valr85 3 90 "'"" 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 1344

Gln Gly Lys Gly Pro Ile Thr Val Pro Val . Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

ro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val65 470 475 480

cag ttc acc caa gct tgc tca age gtc tgg ggc caa tgt ggt ggc.cag 1488

Gln Phe Thr Gln Ala Cys Ser Ser Val Trp Gly Gln Cys Gly Gly Gln485 490 495

aat tgg tcg ggt ccg actAsn Trp Ser Gly Pro Thr500

tcc aac gac tat tac tccSer Asn Asp Tyr Tyr Ser515

tcg tcc acg cgc gcc gcgSer Ser Thr Arg Ala Ala530

tcc cgg. tcg age tcc gcgSer Arg Ser Ser Ser Ala

tgc tgt gct tcc gga ageCys Cys Ala Ser Gly Ser505

cag tgt ctt ccc ggc gctGln Cys Leu Pro Gly Ala520

tcg acg act tet cga gtaSer Thr Thr Ser Arg Val535 540

acg cct cca cct ggt tetThr Pro Pro Pro Gly Ser

aca tgc gtc tac 1536

Thr Cys Val Tyr510

gea age tca age 1584

Ala Ser Ser Ser

525

tcc ccc aca aca 1632

Ser Pro Thr Thr

act act acc aga 1680

Thr Thr Thr Arg545 550 555 560

gta cct cca gtc gga tcg gga acc gct acg tat tca ggc aac cct ttt 1728

Val Pro Pro Val Gly Ser Gly Thr Ala Thr Tyr Ser Gly Asn Pro Phe565 570 575

gtt ggg gtc act cct tgg gcc aat gca tat tac gcc tct gaa gtt age 1776

Val Gly Val Thr Pro Trp Ala Asn Ala Tyr Tyr Ala Ser Glu Val Ser580 585 590

age ctc gct att cct age ttg act gga gcc atg gcc act gct gca gca 1824

Ser Leu Ala Ile Pro Ser Leu Thr Gly Ala Met Ala Thr Ala Ala Ala95 600 605

gct gtc gca aag gtt ccc tct ttt atg tgg cta gat act ctt gac aag . 1872Ala Val Ala Lys Val Pro Ser Phe Met Trp Leu Asp Thr Leu Asp Lys610 615 620

acc cct ctc atg gag caa acc ttg gcc gac ate cgc acc gcc aac aag 1920

Thr Pro Leu Met Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala Asn Lys630 635 640

aat ggc ggt aac tat gcg gga cag ttt gtg gtg tat gac ttg ccg gat 1968

Asn Gly Gly Asn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu Pro Asp645 650 655

cgc gat tgc gct gcc ctt gcc tcg aat ggc gaa tac tct att gcc gat 2016

Arg Asp Cys Ala Ala Leu Ala Ser Asn Gly Glu Tyr Ser Ile Ala Asp660 665 670

ggt ggc gtc gcc aaa tat aag aac tat ate gac acc att cgt caa att 2064

Gly Gly Val Ala Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg Gln Ile675 680 685

gtc gtg gaa tat tcc gat ate cgg acc' ctc ctg gtt att gag cct gac 2112

Val Val Glu Tyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu Pro Asp690 695 700

tct ctt gcc aac ctg gtg acc aac ctc ggt act cca aag tgt gcc aat 2160

Ser Leu Ala Asn Leu Val Thr Asn Leu Gly Thr Pro Lys Cys Ala Asn710 715 720

gct cag tca gcc tac ctt gag tgc ate aac tac gcc gtc aca cag ctg 2208

Ala Gln Ser Ala Tyr Leu Glu Cys Ile Asn Tyr Ala Val Thr Gln Leu725 730 735

aac ctt cca aat gtt gcg atg tat ttg gac gct ggc cat gca gga tgg 2256

Asn Leu Pro Asn Val Ala Met Tyr Leu Asp Ala Gly His Ala Gly Trp740 745 750

ctt ggc tgg ccg gca aac caa gac ccg gcc gct cag cta ttt gca aat 2304

Leu Gly Trp Pro Ala Asn Gln Asp Pro Ala Ala Gln Leu Phe .Ala. Asn755 760 765

gtt tac aag aat gca tcg tct ccg aga gct ctt cgc gga ttg gca acc 2352

Val Tyr Lys Asn Ala Ser Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr770 775 780

aat gtc gcc aac tac aac ggg tgg aac att acc age ccc cca tcg tac 2400Asn Val Ala Asn Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr785 790 795 800acg caa ggc aac gct gtc tac aac gag aag ctg. tac ate cac gct att 2448

Thr Gln Gly Asn Ala Val Tyr Asn Glu Lys Leu Tyr Ile His Ala Ile805 810 815

gga cgt ctt ctt gcc aat cac ggc tgg tcc aac gcc ttc ttc ate act 24 96

Gly Arg Leu Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe Ile Thr820 825 830

gat caa ggt cga tcg gga aag cag cct acc gga cag caa cag tgg gga 254 4

Asp Gln Gly Arg Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly-835 840 845

gac tgg tgc aat gtg ate ggc acc gga ttt ggt att cgc cca tcc gea 2592

Asp Trp Cys Asn Val Ile Gly Thr Gly Phe Gly He Arg Pro Ser Ala850 855 860

aac act ggg gac tcg ttg ctg gat tcg ttt gtc tgg gtc aag cca ggc 2 64 0

Asn Thr Gly Asp Ser Leu Leu Asp Ser Phe Val Trp Val Lys Pro Gly865 870 875 880

gc gag tgt gac ggc acc age gac age agt gcg cca cga ttt gac tcc 2688

Gly Glu Cys Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser885 890 895

cac tgt gcg ctc cca gat gcc ttg caa ccg gcg gct caa gct ggt gct 273 6

His Cys Ala Leu Pro Asp Ala Leu Gln Pro Ala Ala Gln Ala Gly Ala900 905 910

tgg ttc caa gcc tac ttt gtg. cag ctt ctc aca aac gea aac cca tcg 2784

Trp Phe Gln Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn Pro Ser915 920 925

ttc ctg taa _ ' . 2793

Phe Leu930

<210> 86:211> 930

l212> ■ ' PRT /; -- ■■.- V . ^<213> ;;; Seqüência artificial . .

<220> ..... .........

<223> Construção Sintética

<400> 86

Gln Ser Ser Cys Val Ser Ala Trp'.Gly Gln Cys Gly Gly Ile Ser Tyr15. 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 4 0 4 5

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120' 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

_Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 .380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Gln Ala Cys Ser Ser Val Trp Gly Gln Cys Gly Gly Gln485 490 495

Asn Trp Ser Gly Pro Thr Cys Cys Ala Ser Gly Ser Thr Cys Val Tyr500 505 510

Ser Asn Asp Tyr Tyr Ser Gln Cys Leu Pro Gly Ala Ala Ser Ser Ser515 520 525

Ser Ser Thr Arg Ala Ala Ser Thr Thr Ser Arg Val Ser Pro Thr Thr530 535 540Ser Arg Ser Ser Ser Ala Thr Pro Pro Pro Gly Ser Thr Thr Thr Arg545 550 555 560

Val Pro Pro Val Gly Ser Gly Thr Ala Thr Tyr Ser Gly Asn Pro Phe565 570 575

Val Gly Val Thr Pro Trp Ala Asn Ala Tyr Tyr Ala Ser Glu Val Ser580 585 590

Ser Leu Ala Ile Pro Ser Leu Thr Gly Ala Met Ala Thr Ala Ala Ala595 600 605

Ala Val Ala Lys Val Pro Ser Phe Met Trp Leu Asp Thr Leu Asp Lys610 615 620

^fchr Pro Leu Met Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala Asn Lys^^25 630 635 640

Asn Gly Gly Asn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu Pro Asp645 650 655

Arg Asp Cys Ala Ala Leu Ala Ser Asn Gly Glu Tyr Ser Ile Ala Asp660 665 670

Gly Gly Val Ala Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg Gln Ile675 680 685

Val Val Glu Tyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu Pro Asp

690 695 700

^Ber Leu Ala Asn Leu Val Thr Asn Leu Gly Thr Pro Lvs Cys Ala Asn^ 7 05 710 715 720

Ala Gln Ser Ala Tyr Leu Glu Cys Ile Asn Tyr Ala Val Thr Gln Leu725 730 735

Asn Leu Pro Asn Val Ala Met Tyr Leu Asp Ala Gly His Ala Gly Trp740 745 750

Leu Gly Trp Pro Ala Asn Gln Asp Pro Ala Ala Gln Leu Phe Ala Asn

755 760 765

Val Tyr Lys Asn Ala Ser Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr770 775 780Asn Val Ala Asn Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr785 790 795 800

Thr Gln Gly Asn Ala Val Tyr Asn Glu Lys Leu Tyr Ile His Ala Ile8 0.5 810 815

Gly Arg Leu Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe Ile Thr820 825 830

Asp Gln Gly Arg Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly835 840 845

Asp Trp Cys Asn Val Ile Gly Thr Gly Phe Gly Ile Arg Pro Ser Ala850 855 ' 860

Φ

sn Thr Gly Asp Ser Leu Leu Asp Ser Phe Val Trp Val Lys Pro Gly5 870 875 880

Gly Glu Cys Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser885 890 895

His Cys Ala Leu Pro Asp Ala Leu Gln Pro Ala Ala Gln Ala Gly Ala900 905 910

Trp Phe Gln Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn Pro Ser915 920 925

Phe Leu930

Í10> 87!ll> 2931<212> DNA

<213> ' .Seqüêríciàrártificral: í

<220>

< 2 2 3 > Proteína dé fusão':

<220>

<221> CDS<222> (1)..(2931)

<4 00> 87

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aacThr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30tcg tac tac tac cag tgc ata cca gca aca gct gtg agt act tca act 144Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

acc aca gtg aca tct ccc tct age tet ggt tcg tet tet gcc aac acg 192Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gca aca cag 240Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctc 288Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

jag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

tcc atg tgc ãag tcc ggg acg atg tgg gga gag caa cac acc gta act 432Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 480Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age· tgg aca gac cca atg ctg.ggc tct acc tgc gac 576Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Jcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gca tcc ggc aat ccc gac aac tac ctc tct 720Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270gta gac age tgt ccc tgc aat gcc aàt tca aaa tgg tgc. tgt aag cgg 864

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 10.5 6

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

g att CGC ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

1 Ile Pro Ile Arg Tyr Arg Arg Vàl Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 124 8

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

|g ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 134 4

Ln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act- gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc ggc tcg act tac tcc agt gga tet tet tcg ggg tcg ggg 1488

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

tet age tcc age tcg agt tcg act acc act aag gcc açt tcg acg acc 1536

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lvs Ala Thr Ser Thr Thr500 505 510

ttg aag act acc tcg acc acc age agt gga age agt tcg aca tcg gcg 1584Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

gcg caa gct tgc tca age gtc tgg ggc caa tgt ggt ggc cag aat tgg 1632

Ala Gln Ala Cys Ser Ser Val Trp Gly Gln Cys Gly Gly Gln Asn Trp530 535 540

tcg ggt ccg act tgc tgt gct tcc gga age aca tgc gtc tac tcc aac 1680

Ser Gly Pro Thr Cys Cys Ala Ser Gl-y. Ser Thr Cys Val Tyr Ser Asn545 550 555 560

gac tat tac tcc cag tgt ctt ccç ggc gct gea age tca age tcg tcc 1728

Asp Tyr Tyr Ser Gln Cys Leu Pro Gly Ala Ala Ser Ser Ser Ser Ser565 570 575

acg cgc gcc gcg tcg acg act tet cga gta tcc ccc aca aca tcc cgg 177.6

Thr Arg Ala Ala Ser Thr Thr Ser Arg Val Ser Pro Thr Thr Ser Arg580 585 590

tcg age tcc gcg acg cct cca cct ggt tet act act acc aga gta cct 1824

er Ser Ser Ala Thr Pro Pro Pro Gly Ser Thr Thr Thr Arg Val Pro595 600 ; 605

cca gtc gga tcg gga acc gct acg tat tca ggc aac cct ttt gtt ggg 1872

Pro Val Gly Ser Gly Thr Ala Thr Tyr Ser Gly Asn Pro Phe Val Gly610 615 620

gtc act cct tgg gcc aat gea tat tac gcc .tet gaa gtt age age etc 1920

Val Thr Pro Trp Ala.Asn Ala Tyr Tyr Ala Ser Glu Val Ser Ser Leu625 630 635 640

gct att cct age ttg act gga gcc atg gcc act gct gea gea gct gtc 1968

Ala Ile Pro Ser Leu Thr Gly Ala Met Ala Thr Ala Ala Ala Ala Val645 650 655

gea aag gtt ccc tet ttt atg tgg cta gat act ctt gac aag acc cct 2016

Ala Lys Val Pro Ser Phe Met Trp Leu Asp Thr Leu Asp Lys Thr Pro660 665 670

Φ

etc atg gag caa acc ttg gcc gac ate cgc acc gcc aac aag aat ggc 2064

u Met Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala Asn Lys Asn Gly675 680 685

ggt aac tat gcg gga cag ttt gtg gtg. tat gac ttg ccg gat cgc gat 2112

Gly Asn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu Pro Asp Arg Asp690 695 700

tgc gct gcc ctt gcc tcg aat ggc gaa tac tet att gcc gat ggt ggc 2160

Cys Ala Ala Leu Ala Ser Asn Gly Glu Tyr Ser Ile Ala Asp Gly Gly705 710 715 720

gtc gcc aaa tat aag aac tat ate gac acc att cgt caa att gtc gtg 2208

Val Ala Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg Gln Ile Val Val .

725 730 735

gaa tat tcc gat ate cgg acc ctc ctg gtt att gag cct gac tet ctt 2256

Glu Tyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu Pro Asp Ser Leu740 745 750

gcc aac ctg gtg acc aac ctc ggt act cca aag tgt gcc aat gct cagAla Asn Leu Val Thr Asn Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln

2304755 760 765

tca gcc tac ctt gag tgc ate aac tac gcc gtc aca cag ctg aac ctt 2352

Ser Ala Tyr Leu Glu Cys Ile Asn Tyr Ala Val Thr Gln Leu Asn Leu770 775 780

oca aat gtt gcg atg tat ttg gac gct ggc cat gea gga tgg ctt ggc 2400

Pro Asn Val Ala Met Tyr Leu Asp Ala Gly His Ala Gly Trp Leu Gly785 790 795 800

tgg ccg gea aac caa gac ccg gcc gct cag cta ttt gea aat gtt tac 2448

Trp Pro Ala Asn Gln Asp Pro Ala Ala Gln Leu Phe Ala Asn Val Tyr. 805 810 815

aag aat gea tcg tet ccg aga gct ctt cgc gga ttg gea acc aat gtc 24 96

Lys Asn Ala Ser Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr Asn Val820 825 830

gcc aac tac aac ggg tgg aac att acc age ccc cca tcg tac acg caa 2544

Ala Asn Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln835 840 845

ggc aac gct gtc tac aac gag aag ctg tac ate cac gct att gga cgt 2592

Gly Asn Ala Val Tyr Asn Glu Lys Leu Tyr Ile His Ala Ile Gly Arg850 855 860

ctt ctt gcc aat cac ggc tgg tcc aac gcc ttc ttc ate act gat caa 2640

Leu Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe Ile Thr Asp Gln865 870 . 875 880

ggt cga tcg gga aag cag cct acc gga cag.caa cag tgg gga gac tgg 2688

Gly Ar.g Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp885 890 895

tgc aat gtg ate ggc acc gga ttt ggt att cgc cca tcc gea aac act 2736

Cys Asn Val Ile Gly Thr Gly Phe Gly Ile Arg P.ro Ser Ala Asn Thr900 905 910

ggg gac tcg ttg ctg gat tcg ttt gtc tgg gtc aag cca ggc ggc gag 2784

JSly Asp Ser Leu Leu Asp Ser Phe Val Trp Val Lys Pro Gly Gly Glu915 920 925

tgt gac ggc acc age gac age agt gcg cca cga ttt gac tcc cac tgt 2832

Cys Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser His Cys930 935 940

gcg ctc cca gat gcc ttg caa ccg gcg gct caa gct ggt gct tgg ttc 2880

Ala Leu Pro. Asp Ala Leu Gln Pro Ala Ala Gln Ala Gly Ala Trp Phe945 950 955 960

caa gcc tac ttt gtg cag ctt ctc aca aac gea aac cca tcg ttc ctg 2928

Gln Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu965 97a 975

taa 2931

<210> 88

<211> 976

<212> PRT

<213> Seqüência artificiai<220>

<223> Construção Sintética<400> 88

Gln Ser Ser Cys Val Ser Ala Trp.Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu.Ile Asn20 25 30

Ser Tyr Tyç Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr' Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys'Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val.Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr1 Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

ir Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys . Pro Gly Asn355 ' 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ter Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 .455 460Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

Ala Gln Ala Cys Ser Ser Val Trp Gly Gln Cys Gly Gly Gln Asn Trp530 535 540

ír Gly Pro Thr Cys Cys Ala Ser Gly Ser Thr Cys Val Tyr Ser AsnΓ45 550 555 ' 560

Asp Tyr Tyr Ser Gln Cys Leu Pro Gly Ala Ala Ser Ser Ser Ser Ser565 570 575

Thr Arg Ala Ala Ser Thr Thr Ser Arg Val Ser Pro Thr Thr Ser Arg580- 585 590

Ser Ser Ser Ala Thr Pro Pro Pro Gly Ser Thr Thr Thr Arg Val Pro595 600 605

Pro Val Gly Ser Gly Thr Ala Thr Tyr Ser Gly Asn Pro Phe Val Gly

610 615 620

fl^tl Thr Pro Trp Ala Asn Ala Tyr Tyr Ala Ser Glu Val Ser Ser Leu

625 630 635 640

Ala Ile Pro Ser Leu Thr Gly Ala Met Ala Thr Ala Ala Ala Ala Val645 650 655

Ala Lys Val Pro Ser Phe Met Trp Leu Asp Thr Leu Asp Lys Thr Pro660 665 670

Leu Met Glu Gln Thr Leu Ala Asp Ile Arg Thr Ala Asn Lys Asn Gly675 680 685

Gly Asn Tyr Ala Gly Gln Phe Val Val Tyr Asp Leu Pro Asp Arg Asp690 695 700

Cys Ala Ala Leu Ala Ser Asn Gly Glu Tyr Ser Ile Ala Asp Gly Gly705 710 715 720

Val Ala Lys Tyr Lys Asn Tyr Ile Asp Thr Ile Arg Gln Ile Val Val725 730 735

Glu Tyr Ser Asp Ile Arg Thr Leu Leu Val Ile Glu Pro Asp Ser Leu740 745 750

Ala Asn Leu Val Thr Asn Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln755 760 765

Ser Ala Tyr Leu Glu Cys Ile Asn Tyr Ala Val Thr Gln Leu Asn Leu770 775 780

Pro Asn Val Ala Met Tyr Leu Asp Ala Gly His Ala Gly Trp Leu Gly785 790 795 800

Trp Pro Ala Asn Gln Asp Pro Ala Ala Gln. Leu Phe Ala Asn Val Tyr805 810 815

Lys Asn Ala Ser Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr Asn Val820 825 830

Ala Asn- Tyr Asn Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln835 840 845

Gly Asn Ala Val Tyr Asn Glu Lys Leu Tyr Ile His Ala Ile Gly Arg850 855 860

Leu Leu Ala Asn His Gly Trp Ser Asn Ala Phe Phe Ile Thr Asp Gln65 870 875 880

Gly Arg Ser Gly Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp885 890 895

Cys Asn Val Ile Gly Thr Gly Phe Gly Ile Arg Pro Ser Ala Asn Thr900 905 910

Gly Asp Ser Leu Leu Asp Ser Phe Val Trp Val Lys Pro Gly Gly Glu915 920 925

Cys Asp Gly Thr Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser His Cys930 935 940

Ala Leu Pro Asp Ala Leu Gln Pro Ala Ala Gln Ala Gly Ala Trp Phe945 950 955 960Gln Ala Tyr Phe Val Gln Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu965 970 975

<210> 89

<211> 2679

<212> /BNft ________

<213> Séqüêíiciá àríificíkí

<22o>

<223> Proteína dé fusão

<220>

<221> CDS

<222> (I)(2679)

400> 89

ag age age tgc gtc tcg gct tgg ggt caa tgt» ggc ggt att tet tat

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

48

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aacThr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

96

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca actSer Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

144

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acgThr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

192

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cagSer Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

240

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctcAsn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

288

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tccVal Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

336

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tccGlu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

384

tcc atg tgc aag'tcc ggg acg atg tgg gga gag caa cac acc gta actSer Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

432

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg accSer Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

480

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac

528Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 . 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 57 6

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gea tcc ggc aat ccc gac aac tac ctc tet 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 7 68

s Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 8 64

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

_aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008 .

^ys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 . 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc. ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser.Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 134 4

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro AIa Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc ccc ggc gct gea age tca age tcg tcc acg cgc gcc gcg 1488

Gln Phe Thr Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala 485 490 49-5

tcg acg act tet cga gta tcc ccc aca aca tcc cgg tcg age tcc gcg 1536

Ser Thr Thr Ser Arg Val Ser Pro Thr ThrSer Arg Ser Ser Ser Ala500 505 510

acg cct cca cct ggt tet act act acc aga gta cct cea gtc gga tcg 1584

Thr Pro Pro Pro Gly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser515 520 525

gga acc gct acg tat tca ggc aac cct ttt gtt ggg gtc act cct tgg 1632

Gly Thr Ala Thr Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp530 535 540

gcc aat gea

Ala Asn Ala545

ttg act ggaeu Thr Gly

tet ttt atgSer Phe Met

acc ttg gccThr Leu Ala595

gga cag tttGly Gln Phe610

gcc tcg aatAla Ser Asn625

aag aac tatLys Asn Tyr

tat tac gccTyr Tyr Ala550

gcc atg gccAla Met Ala565

tgg cta gatTrp Leu Asp580

gac ate cgcAsp Ile Arg

gtg gtg tatVal Val Tyr

ggc gaa tacGly Glu Tyr630

ate gac accIle Asp Thr645

tet gaa gttSer Glu Val

act gct geaThr Ala Ala

act ctt gacThr Leu Asp585

acc gcc aacThr Ala Asn600

gac ttg ccgAsp Leu Pro615

tet att gccSer Ile Ala

att cgt caaIle Arg Gln

age age ctcSer Ser Leu555

gea gct gtcAla Ala Val5 70

aag acc cctLys Thr Pro

aag aat ggcLys Asn Gly

gat cgc gatAsp Arg Asp620

gat ggt ggcAsp Gly Gly635

att gtc gtgIle Val Val650

gct att cctAla Ile Pro

gea aag gttAla Lys Val575

ctc atg gagLeu Met Glu590

ggt aac tatGly Asn Tyr605

tgc gct gccCys Ala Ala

gtc gcc aaaVal Ala Lys

gaa tat tccGlu Tyr Ser655

age 1680

Ser

560

ccc 1728

Pro

caa 1776

Gln

gcg 1824

Ala

ctt 1872

Leu

tat 1920

Tyr

640

gat 1968

Aspate cgg acc ctc ctg gtt att gag cct gac tet ctt gcc aac ctg gtg 2016

Ile Arg Thr Leu Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val660 665 670

acc aac ctc ggt act cca aag tgt gcc aat gct cag tca gcc tac ctt 2064

Thr Asn Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala Tyr Leu675 680 685

gag tgc ate aac tac gcc gtc aca cag ctg aac ctt cca aat gtt gcg 2112

Glu Cys Ile Asn Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala690 695 700

atg tat ttg gac gct ggc cat gea gga tgg ctt ggc tgg ccg gea aac 2160

Met Tyr Leu Asp Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn705 710 715 720

caa gac ccg gcc gct cag cta ttt gea aat gtt tac aag aat gea tcg 2208

Gln Asp Pro Ala Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser725 730 735

Jt ccg aga gct ctt cgc gga ttg gea acc aat gtc gcc aac tac aac 225 6

Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr Asn Val Ala Asn Tyr Asn740 745 750

ggg tgg aac att acc age ccc cca tcg tac acg caa ggc aac gct gtc 2304·

Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln Gly Asn Ala Val755 760 765

tac aac gag aag ctg tac ate cac gct att gga cgt ctt ctt gcc aat 2352

Tyr Asn Glu Lys Leu Tyr Ile His Ala Ile Gly Arg Leu Leu Ala Asn770 775 780

cac ggc tgg tcc aac gcc ttc ttc ate act gat caa ggt cga tcg gga 2400

His Gly Trp Ser Asn1Ala Phe Phé Ile Thr Asp Gln Gly Arg Ser Gly785 790 795 800

aag cag cct acc gga cag caa cag tgg gga gac tgg tgc aat gtg ate 2448

Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile805 810 815

fc acc gga ttt ggt att cgc cca tcc gea aac act ggg ga.c tcg ttg 24 96

Gly Thr Gly Phe Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu820 825 830

ctg gat tcg ttt gtc tgg. gtc aag cca ggc ggc gag tgt gac ggc acc 2544

Leu Asp Ser Phe Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr835 840 845

age gac age agt gcg cca cga ttt gac tcc cac tgt gcg ctc cca gat 2592

Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp850 855 860

gcc ttg caa ccg gcg gct caa gct ggt gct tgg ttc caa gcc tac ttt 2640

Ala Leu Gln Pro Ala Ala Gln Ala Gly Ala Trp Phe Gln Ala Tyr Phe865 870 875 880

gtg cag ctt ctc aca. aac gea aac cca tcg ttc ctg taa 2679 Val Gln Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu885 890<210> 90

<211> 892

<212> PRT

<213> Seqüência artificial

<220>

<223> Construção Sintética

<400> 90

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr

1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu-Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala275 280

Pro Pro Pro Pro Pro Phe Phe Ser290 295

Thr Arg Pro Gly Gly Ser Gly Ala305 310

Asn Ser Lys Trp Cys Cys Lys Arg285

Pro Pro Ser Asn Gly Gln Asn Leu300

Asp His Cys Gly Glu Ile Asp Phe315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 . 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415.

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala. Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala485 490 495

Ser Thr Thr Ser Arg Val Ser Pro Thr Thr Ser Arg Ser Ser Ser Ala500 505 510

Thr Pro Pro Pro Gly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser515 520 525

Iy Thr Ala Thr Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp530 535 540

Ala Asn Ala Tyr Tyr Ala Ser Glu Val Ser Ser Leu Ala Ile Pro Ser545 550 555 560

Leu Thr Gly Ala Met Ala Thr Ala Ala Ala Ala Val Ala Lys Val Pro565 570 575

Ser Phe Met Trp Leu Asp Thr Leu Asp Lys Thr Pro Leu Met Glu Gln580 585 590

Thr Leu Ala Asp Ile Arg Thr Ala Asn Lys Asn Gly Gly Asn Tyr Ala595 600 605

Gly Gln Phe Val Val Tyr Asp Leu Pro Asp Arg Asp Cys Ala Ala Leu610 615 620

Ala Ser Asn Gly Glu Tyr Ser Ile Ala Asp Gly Gly Val Ala Lys Tyr625 630 635 640

Lys Asn Tyr Ile Asp Thr Ile Arg Gln Ile Val Val Glu Tyr Ser Asp645 650 655

Ile Arg Thr Leu Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val660 665 670

Thr Asn Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala Tyr Leu675 680 685Glu Cys Ile Asn Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala690 695 700

Met Tyr Leu Asp Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn705 710 715 720

Gln Asp Pro Ala Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser725 730 735

Ser Pro Arg Ala Leu Arg Gly Leu Ala Thr Asn Val Ala Asn Tyr Asn740 745 . 750

Gly Trp Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln Gly Asn Ala Val755 760 765

m

r Asn Glu Lys Leu Tyr Ile His Ala Ile Gly Arg Leu Leu Ala Asn770 775 780

His Gly Trp Ser Asn Ala Phe Phe Ile Thr Asp Gln Gly Arg Ser Gly785 790 795 800

Lys Gln Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile805 810 815

Gly Thr Gly Phe Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu820 825 830

Leu Asp Ser Phe Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr835 840 845

Ser Asp Ser Ser Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp850 855 860

Ala Leu Gln. Pro Ala Ala Gln Ala Gly Ala Trp Phe Gln Ala Tyr Phe865 870 875 880

Val Gln Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu885 890

<210> 91<211> 2817<212> DNA

<213> Seqüência artificial

< 2 2 0 >

< 2 2 3> Proteína de fusão<220>

<221> CDS<222> (1) . . (2817)

<400> 91

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat 4 8

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac 96

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca act 144

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acg 192

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cag 240

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctc 288

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

gtt gat aac gtt tgc tgc cca tac tac.tgt ctc tcg gat aat gaa tcc 336

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 432

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 4 80

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc .aag aac 528

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 57 6

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act.cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220ttc tgg cct tcc ctg gct gca tcc ggc aat ccc gac aac tac ctc tct _ 720

Phe Trp Pro Ser-Leu Ala Ala·Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 7 68

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 8 64

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser.Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

^ca,aga Cca ggc ggc age ggc gca.gac cac tgc ggc gaa ate gac ttc 960

ir Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340- 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 , 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat. tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ígc gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

er Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctç gag cac gat ccg aac 124 8

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tct tgg gtc ctc ccg 1296

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 134 4

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc. gag ggc ttt tgg tat att gat ctg gga gtg 14 4 0Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc ggc tcg act tac tcc agt gga tct tct tcg ggg tcg ggg 1488

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

tct age tcc age tcg agt tcg act acc act aag gcc act tcg acg acc 1536

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

ttg aag act acc tcg acc acc age agt gga age agt tcg aca tcg gcg 1584

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

gcg ccc ggc gct gea age tca age tcg tcc acg cgc gcc gcg tcg acg 1632

Ala Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr530 535 540

ct tct cga gta7 tcc ccc aca aca tcc cgg tcg age tcc gcg acg cct 1680

ihr Ser Arg Val Ser Pro Thr Thr Ser Arg Ser Ser Ser Ala Thr'Pro45 550 555 560

cca cct ggt tct act act acc aga gta cct cca gtc gga tcg gga acc . 1728

Pro Pro Gly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser Gly Thr

565 570 575

gct acg tat tca ggc aac cct ttt gtt ggg gtc act cct tgg gcc.aat 1776

Ala Thr Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp Ala Asn

580 585 590

gea tat tac gcc tct gaa gtt age age ctc gct att cct age ttg actAla Tyr Tyr Ala Ser Glu Val Ser Ser Leu Ala Ile Pro Ser Leu Thr595 600 605

1824

gga gcc atg gcc act gct gea gea gct gtc gea aag gtt ccc tct ttt 1872

Gly Ala Met Ala Thr Ala Ala Ala Ala Val Ala Lys Val Pro Ser Phe610 615 620

itg tgg cta gat act ctt gac aag acc cct ctc atg gag caa acc ttg 1920

Iet Trp Leu Asp Thr Leu Asp Lys Thr Pro Leu Met Glu Gln Thr Leu625 630 635 640

gcc gac ate cgc acc gcc aac aag aat ggc ggt aac tat gcg gga cag 1968

Ala Asp Ile Arg Thr Ala Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln645 650 655

ttt gtg gtg tat gac ttg ccg gat cgc gat tgc gct gcc ctt gcc tcg 2016

Phe Val Val Tyr Asp Leu Pro Asp Arg Asp Cys Ala Ala Leu Ala Ser660 665 670

aat ggc gaa tac tct att gcc gat ggt ggc gtc gcc aaa tat aag aac 2064

Asn Gly Glu Tyr Ser Ile Ala Asp Gly Gly Val Ala Lys Tyr Lys Asn675 680 685

tat ate gac acc att cgt caa att gtc gtg gaa tat tcc gat ate cgg 2112

Tyr Ile Asp Thr Ile Arg Gln Ile Val Val Glu Tyr Ser Asp Ile Arg690 695 700

acc ctc ctg gtt att gag cct gac tct ctt gcc aac ctg gtg acc aac 2160

Thr Leu Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val Thr Asn705 710 715 720

ctc ggt act cca aag tgt gcc aat gct .cag tca gcc tac ctt gag tgc 2208

Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala Tyr Leu Glu Cys725 730 735

ate aac tac gcc gtc aca cag ctg aac ctt cca aat gtt gcg atg tat 2256

Ile Asn Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala Met Tyr740 745 750

ttg gac gct ggc cat gea gga tgg ctt ggc tgg ccg gea aac caa gac 2304

Leu Asp Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp755 760 765

ccg gcc gct cag cta ttt gea aat gtt tac aag aat gea tcg tet ccg 2352

Pro Ala Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro770 775 780

aga gct ctt cgc gga ttg gea acc aat gtc gcc aac tac aac ggg tgg 2400

g Ala Leu Arg Gly Leu Ala Thr Asn Val Ala Asn Tyr Asn Gly Trp5 790 795 800

aac att acc age ccc cca tcg tac acg caa ggc aac gct gtc tac aac 24 4 8Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln Gly Asn Ala Val Tyr Asn805 810 815

gag aag ctg tac ate cac gct att gga cgt ctt ctt gcc aat cac ggc 24 96Glu Lys Leu Tyr Ile His Ala Ile Gly Arg Leu Leu Ala Asn His Gly820 825 83.0

tgg tcc aac gcc ttc ttc ate act gat caa ggt cga tcg gga aag cag 254 4

Trp Ser Asn Ala Phe Phe Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln835 840 845

cet acc gga cag caa cag tgg gga gac tgg tgc aat gtg ate ggc acc 2592

Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile Gly Thr850 855 860

gga ttt ggt att cgc cca tcc gea aac act ggg gac tcg ttg ctg gat 2640

Uy Phe Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp165 '870 875 880

tcg ttt gtc tgg gtc aag cca ggc ggc gag tgt gac ggc acc age gac 2688

Ser Phe Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp885 890 895

age agt gcg cca cga ttt gac tcc cac tgt gcg etc cca gat gcc ttg 27 36

Ser Ser Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp Ala Leu900 905 910

caa ccg gcg gct caa gct ggt gct tgg ttc caa gcc tac ttt gtg cag 2784

Gln Pro Ala Ala Gln Ala Gly Ala Trp Phe Gln Ala Tyr Phe Val Gln915 920 925

ctt ctc aca aac gea aac cca tcg ttc ctg taa 2817

Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu930 935

<210> 92

<211> 938<212> PRT

<213> Seqüência artificial

<220>

<223> Cpnstrução Sintética<400> 92

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr15 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

[hr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser-Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

sr Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp HisTyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210

215

220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser.325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys P-ro Lys Pro Gly Asn355 360 365

:ie Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460Pro Pro Ala Thr Ala Val Glu Gly Phe. Trp Tyr.Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

Ala Pro Gly Ala Ala Ser Ser Ser Ser Ser Thr Arg Ala Ala Ser Thr530 535 540

Thr Ser Arg Val Ser Pro Thr Thr Ser Arg Ser Ser Ser Ala Thr Pro545 550 555 560

Pro Pro Gly Ser Thr Thr Thr Arg Val Pro Pro Val Gly Ser Gly Thr565 570 575

Ala Thr Tyr Ser Gly Asn Pro Phe Val Gly Val Thr Pro Trp Ala Asn580 585 590

Ala Tyr Tyr Ala Ser Glu Val Ser Ser Leu Ala Ile Pro Ser Leu Thr595 600 605

Gly Ala Met Ala Thr Ala Ala Ala Ala Val Ala Lys Val Pro Ser Phe610 615 620

Met Trp Leu Asp Thr Leu Asp Lys Thr Pro Leu Met Glu Gln Thr Leu625 630 635 640

Ala Asp Ile Arg Thr Ala Asn Lys Asn Gly Gly Asn Tyr Ala Gly Gln645 650 655

Phe Val Val Tyr Asp Leu Pro Asp Arg Asp Cys Ala Ala Leu Ala Ser660 665 670

Asn Gly Glu Tyr Ser Ile Ala Asp Gly Gly Val Ala Lys Tyr Lys Asn675 680 685

Tyr Ile Asp Thr Ile Arg Gln Ile Val Val Glu Tyr Ser Asp Ile Arg690 695 700Thr Leu Leu Val Ile Glu Pro Asp Ser Leu Ala Asn Leu Val Thr Asn705 710 715 720

Leu Gly Thr Pro Lys Cys Ala Asn Ala Gln Ser Ala Tyr Leu Glu Cys725 . 730 735

Ile Asn Tyr Ala Val Thr Gln Leu Asn Leu Pro Asn Val Ala Met Tyr740 745 750

Leu Asp Ala Gly His Ala Gly Trp Leu Gly Trp Pro Ala Asn Gln Asp755 760 765

Pro Ala Ala Gln Leu Phe Ala Asn Val Tyr Lys Asn Ala Ser Ser Pro770 775 780

Frg Ala Leu Arg Gly Leu Ala Thr Asn Val Ala Asn Tyr Asn Gly Trp785 790 795 800

Asn Ile Thr Ser Pro Pro Ser Tyr Thr Gln Gly Asn Ala Val Tyr Asn805 810 815

Glu Lys Leu Tyr Ile His Ala Ile Gly Arg Leu Leu Ala Asn His Gly820 825 830

Trp Ser Asn Ala Phe Phe Ile Thr Asp Gln Gly Arg Ser Gly Lys Gln835 840 845

Pro Thr Gly Gln Gln Gln Trp Gly Asp Trp Cys Asn Val Ile Gly Thr850 855 860

Sly Phe Gly Ile Arg Pro Ser Ala Asn Thr Gly Asp Ser Leu Leu Asp865 870 875 880

Ser Phe Val Trp Val Lys Pro Gly Gly Glu Cys Asp Gly Thr Ser Asp885 890 895

Ser Ser Ala Pro Arg Phe Asp Ser His Cys Ala Leu Pro Asp Ala Leu900 905 910

Gln Pro Ala Ala Gln Ala Gly Ala Trp Phe Gln Ala Tyr Phe Val' Gln915 920 925

Leu Leu Thr Asn Ala Asn Pro Ser Phe Leu930 935<210> 93

<211> 2763

<212> DNA

<213> Seqüêiíciá artificial

<220>

<223> Proteína de fusão .

<220><221><222>

CDS

(1)..(2763)

<400> 93

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

48

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aacThr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

96

tcg tac tac tac cag tgc .ata cca gea aca gct gtg agt act tca actSer Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 4 0 4 5

144

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acgThr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

192

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cagSer Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

240

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct etcAsn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

288

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc^Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

336

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tccGlu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

384

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta actSer Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

432

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg accSer Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

480

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aacSer Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 ' 175

528

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gacSer Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

576gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gca tcc ggc aat ccc gac aac tac ctc tct 720Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tác gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 864Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gca gac cac tgc ggc gaa ate gac ttc 960Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg .ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

jtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104fal Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tct tgg gtc ctc ccg 1296Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg Ί34 4Gln Gly Lys Gly Pro He. Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc cag caa ccg ggt acc age acc ccc gag gtc cat ccc aag 1488

Gln Phe Thr Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys485 490 495

ttg aca acc tac aag tgt aca aag tcc ggg ggg tgc gtg gcc cag gac 1536

Leu Thr Thr Tyr Lys Cys Thr Lys Ser Gly Gly Cys Val Ala Gln Asp500 505 510

icc tcg gtg gtc ctt gac tgg aac tac cgc tgg atg cac gac gea aac 1584)hr Ser Val Val Leu Asp Trp Asn Tyr Arg Trp Met His Asp Ala Asn515 520 525

tac aac tcg tgc acc gtc aac ggc ggc gtc aac acc acg ctc tgc cct 1632

Tyr Asn Ser Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro530 535 540

gac gag gcg acc tgt ggc aag aac tgc ttc ate gag ggc gtc gac tac 1680

Asp Glu Ala Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr545 550 555 560

gcc gcc tcg ggc gtc acg acc tcg ggc age age ctc acc atg aac cág 1728

Ala Ala Ser Gly Val Thr Thr Ser Gly Ser Ser Leu Thr- Met Asn Gln565 570 575

tac atg ccc age age tet ggc ggc tac age age gtc tet cct cgg ctg 1776

Tyr Met Pro Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu580 585 590

^at ctc ctg gac tet gac ggt gag tac gtg atg ctg aag ctc aac ggc 1824

/r Leu Leu Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly595 600 605

cag gag ctg age ttc gac gtc gac ctc tet gct ctg ccg tgt gga gag 1872

Gln Glu Leu Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu610 615 620

aac ggc tcg ctc tac ctg tet cag atg gac gag aac ggg ggc gcc aac 1920

Asn Gly Ser Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn625 630 635 640

cag tat aac acg gcc ggt gcc aac tac ggg age ggc tac tgc gat gct . 1968Gln Tyr Asn Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala645 650 655

cag tgc ccc gtc cag aca tgg agg aac ggc acc ctc aac act age cac 2016

Gln Cys Pro Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His660 665 670

cag ggc ttc tgc tgc aac gag atg gat ate ctg gag ggc aac tcg agg

2064Gln Gly Phe Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg675 680 685

gcg aat gcc ttg acc cct cac tct tgc acg gcc acg gcc tgc gac tct 2112

Ala Asn Ala Leu Thr Pro His Ser Cys Thr Ala Thr Ala Cys Asp Ser690 695 700

gcc ggt tgc ggc ttc aac ccc tat ggc age ggc tac aaa age tac tac 2160

Ala Gly Cys Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr705 710 715 720

ggc ccc gga gat acc gtt gac acc tcc aag acc ttc acc ate ate acc 2208

Gly Pro Gly Asp Thr Val Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr725 730 735

cag ttc aac acg gac aac ggc tcg ccc tcg ggc aac ctt gtg age ate 2256Gln Phe Asn Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile740 745 750

acc cgc aag tac cag caa aac ggc gtc gac ate ccc.age gcc cag ccc 2304

Thr Arg Lys.Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro755 760 765

ggc ggc gac acc ate tcg tcc tgc ccg tcc gcc tca gcc tac ggc ggc 2352Gly Gly Asp Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly770 775 780

ctc gcc acc atg ggc aag gcc ctg age age ggc atg gtg etc gtg.ttc 2 4 00

Leu Ala Thr Met Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe785 790 795 800

age att tgg aac gac aac age cag tac atg aac tgg ctc gac age ggc 2448

Ser Ile Trp Asn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly805 810 815

aac gcc ggc ccc tgc age age acc gag ggc aac cca tcc aac ate ctg 24 96

Asn Ala Gly Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu820 825 830

gcc aac aac ccc aac acg cac gtc gtc ttc tcc aac ate cgc tgg gga 2544

JVla Asn Asn Pro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly835 840 845

gac att ggg tct act acg aac tcg act gcg ccc ccg ccc ccg cct gcg 2592

Asp Ile Gly Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala850 855 860

tcc age acg acg ttt tcg act aca cgg agg age tcg acg act tcg age 2640

Ser Ser Thr Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser865 870 875 880

age ccg age tgc acg cag act cac tgg ggg cag tgc ggt ggc att ggg 2 688

Ser Pro Ser Cys Thr Gln Thr His Trp Gly Gln Cys Gly Gly Ile Gly885 890 895

tac age ggg tgc aag acg tgc acg tcg ggc act acg tgc cag tat age 2736

Tyr Ser Gly Cys Lys Thr Cys Thr Ser Gly Thr-Thr Cys Gln Tyr Ser900 905 910

aac gac tac tac tcg caa tgc ctt tagAsn Asp Tyr Tyr Ser Gln Cys Leu

2763915 920

<210> 94<211> 920<212> PRT<213> Sequencia artificial

<220> <223> Construção. Sintética

<400> 94

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 -60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

G1u Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

[al Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 ' 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

jal Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro'Val Ser Met Arg Leu Thr Ala435

440

445

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys4 85 4 90 4 95

Leu Thr Thr Tyr Lys Cys Thr Lys Ser Gly Gly Cys Val Ala Gln Asp500 505 510

Thr Ser Val Val Leu Asp Trp Asn Tyr Arg Trp Met His Asp Ala Asn515 520 525

Tyr Asn Ser Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro530 535 540

Asp Glu Ala Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr545 550 555 560

Ala Ala Ser Gly Val Thr Thr Ser. Gly Ser Ser Leu Thr Met Asn Gln565 570 575

Tyr Met Pro Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu580 585 590

Tyr Leu Leu Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly595 600 605

Gln Glu Leu Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu610 615 620

Asn Gly Ser Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn625 630 635 640

Gln Tyr Asn Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala645 650 655

Gln Cys Pro Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His660 665 670

Gln Gly Phe Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg675 680 685Ala Asn Ala Leu Thr Pro His Ser Cys Thr Ala Thr Ala Cys Asp Ser690 695 700

Ala Gly Cys Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr705 710 715 720

Gly Pro Gly Asp Thr Val Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr725 730 735

Gln Phe Asn Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile740 745 750

Thr Arg Lys Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro755 760 765

Gly Gly Asp Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly770 775 780

Leu Ala Thr Met Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe785 790 795 800

Ser Ile Trp Asn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly805 810 815

Asn Ala Gly Pro Cys· Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu820 825 830

Ala Asn Asn Pro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly835 840 845

Asp Ile Gly Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala850 855 860

Ser Ser Thr Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser865 870 875 880

Ser Pro Ser Cys Thr Gln Thr His Trp Gly Gln Cys Gly Gly Ile Gly885 890 895

Tyr Ser Gly Cys .Lys Thr Cys Thr Ser Gly Thr Thr Cys Gln Tyr Ser900 905 910

Asn Asp Tyr Tyr Ser Gln Cys Leu915 920<210> 95

<211> 2901

<212> DNA

< 213 > Seqüência artificial

<220><22 3>

Proteína de fusão

<220>

<221> CDS<222> (1)..(2901)

<4 00> 95

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

48

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aacfhr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

96

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca actSer Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

144

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acgThr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

192

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cagSer Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

240

aac cct tat cct ccg gcc aat gcc age tca tgt gga. tcg tgg gct ctcAsn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

288

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc[ai Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

336

gag tcc tgc acg age age tgt acc ggcGlu Ser Cys Thr Ser Ser Cys Thr Gly115 120

tcc atg tgc aag tcc ggg' acg atg tggSer Met Cys Lys Sex Gly Thr Met Trp130 135

tcc aac gag gac tgg cat tac age cgcSer Asn Glu Asp Trp His Tyr Ser Arg145 150

age ggt ggc gcc tgc ggg ttc ggt ctgSer Gly Gly Ala Cys Gly Phe Gly Leu165

agt gtc acc gcg age tgg aca gac ccaSer Val Thr Ala Ser Trp Thr Asp Pro

ggc tgc ggc agt cct gat tcc 384

Gly Cys Gly Ser Pro Asp Ser125

gga gag caa cac acc gta act 432

Gly Glu Gln His Thr Val Thr 140

tca aca cac ttt ggt ctg acc 480

Ser Thr His Phe Gly Leu Thr155 160

tac ggc ctc tgc acc aag aac 528

Tyr Gly Leu Cys Thr Lys Asn170 175

atg ctg ggc tet acc tgc gac 576

Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gca tcc ggc aat ccc gac aac tac ctc tct 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 768

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 864

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat etc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gca gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat- gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tct tgg gtc ctc ccgTyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro 12964 20 425 4 30cag ggc aag gga ccc attGln Gly Lys Gly Pro Ile435

ccc aat ggg cag cag gtgPro Asn Gly Gln Gln Val450

ccg ccg gcg act gcg gtcPro Pro Ala Thr Ala Val465 470

act gtg cct gtt tcg atgThr Val Pro Val Ser Met440

gtt aag gag ggc gcc att

Val Lys Glu Gly Ala Ile

455 460

gag ggc ttt tgg tat attGlu Gly Phe Trp Tyr Ile475

agg ctg acg gcg 1344

Arg Leu Thr Ala

445

acc age tat acc 1392

Thr Ser Tyr Thr

gat ctg gga gtg 1440

Asp Leu Gly Val480

cag ttc acc ggc tcg act tac tcc agt gga tet tet tcg ggg tcg ggg 1488

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

tet age tcc age tcg agt tcg act acc act aag gcc act tcg acg acc 1536

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

m

g aag act acc tcg acc acc age agt gga age agt tcg aca tcg gcg 1584

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

gcg cag caa ccg ggt acc age acc ccc gag gtc cat ccc aag ttg aea 1632

Ala Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys Leu Thr530 535 540

acc tac aag tgt aca aag tcc ggg ggg tgc gtg gcc cag gac acc tcg 1680

Thr Tyr Lys Cys Thr Lys Ser Gly Gly Cys Val Ala Gln Asp Thr Ser545 550 555 560

gtg gtc ctt gac tgg aac tac cgc tgg atg cac gac gea aac tac aac 1728

Val Val Leu Asp Trp Asn Tyr Arg Trp Met His Asp Ala Asn Tyr Asn565 570 575

tcg tgc acc gtc aac ggc ggc gtc aac acc açg ctc tgc cct gac gag 1776

Ser Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro Asp Glu580 585 590

Jcg acc tgt ggc aag aac tgc ttc ate gag ggc gtc gac tac gcc gcc 1824

Ala Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala595 600 605

tcg ggc gtc acg acc tcg ggc age age ctc acc atg aac cag tac atg 1872

Ser.Gly Val Thr Thr Ser Gly Ser Ser Leu Thr Met Asn Gln Tyr Met610 615 620

ccc age age tet ggc ggc tac age age gtc tet cct cgg ctg tat ctc 1920

Pro Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu625 630 635 640

ctg gac tet gac ggt gag tac gtg atg ctg aag ctc aac ggc cag gag 1968

Leu Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly Gln Glu645 650 655

ctg age ttc gac gtc gac ctc tet gct ctg ccg tgt gga gag aac ggc 2016

Leu Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly660 665 670tcg ctc tac ctg tct cag atg gac gag aac ggg ggc gcc aac cag tat -2064Ser Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr675 680 685

aac acg gcc ggt gcc aac tac ggg age ggc tac tgc gat gct cag tgc 2112

Asn Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala Gln Cys690 695 700

ccc gtc cag aca tgg agg aac ggc acc ctc aac act age cac cag ggc - 2160Pro Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His Gln Gly705 710 715 720

ttc tgc tgc aac gag atg gat ate ctg gag ggc aac tcg agg gcg aat 2208

Phe Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn725 730 735

gcc ttg acc cct cac tct tgc acg gcc acg gcc tgc gac tct gcc ggt 2256

Ala Leu Thr Pro His Ser Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly740 745 750

gc ggc ttc aac ccc tat ggc age ggc tac aaa age tac tac ggc ccc 2304ys Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro755 760 765

gga gat acc gtt gac acc tcc aag acc ttc acc ate ate acc cag ttcGly Asp Thr Val Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr Gln Phe770 775 780

2352

aac acg gac aac ggc tcg ccc tcg ggc aac ctt gtg age ate acc cgc 2400Asn Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile Thr Arg785 790 795 800

aag tac cag caa aac ggc gtc gac ate ccc age gcc cag ccc ggc ggc 2448

Lys Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro Gly Gly 805 810 815

gac acc ate tcg tcc tgc ccg tcc gcc tca gcc tac ggc ggc ctc gcc 2496

Asp Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala820 825 830

icc atg ggc aag gcc ctg age age ggc atg gtg ctc gtg ttc age att 2544

PhrMet Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe Ser Ile835 840 845

tgg aac gac aac age cag tac atg aac tgg ctc gac age ggc aac gcc 2592

Trp Asn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala850 855 860

ggc ccc tgc age age acc gag ggc aac cca tcc aac ate ctg gcc aac 2640

Gly Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn865 870 875 880

aac ccc aac acg cac gtc gtc ttc tcc aac ate cgc tgg gga gac att . 2688Asn Pro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly Asp Ile885 890 895

ggg tct act acg aac tcg act gcg ccc ccg ccc ccg cct gcg tcc age 2736

Gly Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser900 905 910

acg acg ttt tcg act aca cgg agg age tcg acg act tcg age age ccg

2784Thr Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser Ser Pro915 920 925

age tgc acg cag act cac tgg ggg cag tgc ggt ggc att ggg tac age 2832

Ser Cys Thr Gln Thr His Trp Gly Gln Cys Gly Gly Ile Gly Tyr Ser930 935 940

ggg tgc aag acg tgc acg tcg ggc act acg tgc cag tat age aac gac 2880

Gly Cys Lys Thr Cys Thr Ser Gly Thr Thr Cys Gln Tyr Ser Asn Asp945 950 95-5 960

tac tac tcg caa tgc ctt tag 2901

Tyr Tyr Ser Gln Cys Leu965

<210> 96

<211> 966

<213> Seqüência artificial

<220> ConstruçãoiSintetica

<400> 96

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Glri Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 4 0 4 5

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

e Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

rhr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

Pro.Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Bro. Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val

165

470

475

480

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

Ala Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys Leu Thr530 535 540

Shr Tyr Lys Cys Thr Lys Ser Gly Gly Cys Val Ala Gln Asp Thr Ser45 550 555 560

Val Val Leu Asp Trp Asn Tyr Arg Trp Met His Asp Ala Asn Tyr Asn565 570 575

Ser Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro Asp Glu580 585 590

Ala Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala595 600 605

Ser Gly Val Thr Thr Ser Gly Ser Ser Leu Thr Met Asn Gln Tyr Met610 615 620

Pro Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu625

630

635

640

Leu Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly Gln Glu645 650 655

Leu Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly660 665 670

Ser Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr675 680 685

Asn Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala Gln Cys690 695 700

Pro Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His Gln Gly705 710 715 720

Phe Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn725 730 735

Ala Leu Thr Pro His Ser Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly740 745 750

Cys Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro755 760 765

Gly Asp Thr Val Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr Gln Phe770 775 780

Asn Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile Thr Arg185 790 795 800

Lys Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro Gly Gly805 810 815

Asp Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala820 825 830

Thr Met Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe Ser Ile835 840 845

Trp Asn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala850 855 860

Gly Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn865 870 875 880Asn Pro Asn Thr His Val Val Phe Ser. Asn Ile Arg Trp Gly Asp Ile885 890 895

Gly Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser900 905 910

Thr Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser Ser Pro915 920 925

Ser Cys Thr Gln Thr His Trp Gly Gln Cys Gly Gly Ile Gly Tyr Ser930 935 940

Gly Cys Lys Thr Cys Thr Ser Gly Thr Thr Cys Gln Tyr Ser Asn Asp945 950 955 960

Tyr Tyr Ser Gln Cys Leu965

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<400> 97

ag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tat 4 8

In Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac 96

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca act 144

Ser Tyr Tyr Tyr Gln Cys Ile ProAla Thr Ala Val Ser Thr Ser Thr35 40 45

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acg 192

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cag 240

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct ctc 288Asn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

gtt gat aac gtt tgc tgc cca tac tac tgt ctc tcg gat aat gaa tcc 336

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tcc 384

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta act 432

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc 4 80

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 . 155 160 .

^gc ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528

er Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn

165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 576

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac gcc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttt gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ttc tgg cct tcc ctg gct gea tcc ggc aat ccc gac aac tac ctc tet 720

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

*

£gc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 7 68

s. Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 8 64

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

aca aga cca ggc ggc age ggc gea gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe

305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248η Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg .1296Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 134 4

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

ccg ccg gcg act gcg ,gtc gag ggc ttt tgg tat att gat ctg gga gtg 14 40

Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr ILe Asp Leu Gly Val465 470 475 480

cag ttc acc cag caa ccg ggt acc age acc ccc gag gtc cat ccc aag 1488

In Phe Thr Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys485 490 495

ttg aca acc tac aag tgt aca aag tcc ggg ggg tgc gtg gcc cag gac 1536

Leu Thr Thr Tyr Lys Cys Thr Lys Ser Gly Gly Cys Val Ala Gln Asp500 505 510

acc tcg gtg gtc ctt gac tgg aac tac cgc tgg atg cac gac gea aac 1584

Thr Ser Val Val Leu Asp Trp. Asn Tyr Arg Trp Met His Asp Ala Asn515 520 525

tac aac tcg tgc acc gtc aac ggc ggc gtc aac acc acg ctc tgc cct 1632

Tyr Asn Ser Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro530 535 540

gac gag gcg acc tgt ggc aag aac tgc ttc ate gag ggc gtc gac tac 1680

Asp Glu Ala Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr545 550 555 560

gcc gcc tcg ggc gtc acg acc tcg ggc age age ctc acc atg aac cag 1728AlaAla Ser Gly Val Thr Thr Ser Gly Ser Ser Leu Thr Met Asn Gln565 570 575tac atg ccc age age tet ggc ggc tac age age gtc tet cct cgg ctg 1776

Tyr Met Pro Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu580 585 590

tat ctc ctg gac tet gac ggt gag tac gtg atg ctg aag ctc aac ggc 1824

Tyr Leu Leu Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly595 600 605

cag gag ctg age ttc gac gtc gac ctc tet gct ctg ccg tgt gga gag 1872

Gln Glu Leu Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu610 615 620

aac ggc tcg ctc tac ctg tet cag atg gac gag aac ggg ggc gcc aac 1920

Asn Gly Ser Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn625 630 635 640

cag tat aac acg gcc ggt gcc aac tac ggg age ggc tac tgc gat gct 1968

Gln Tyr Asn Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala645 650 655

cag tgc ccc gtc cag aca tgg agg.aac ggc acc ctc aac act age cac 2016Gln Cys Pro Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His660 665 .670

cag ggc ttc tgc tgc aac gag atg gat ate ctg gag ggc aac tcg agg 2064Gln Gly Phe Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg675 680 685

gcg aat gcc ttg acc cct cac tet tgc acg gcc acg gcc tgc gac tet 2112

Ala Asn Ala Leu Thr Pro His Ser Cys Thr Ala Thr Ala Cys Asp Ser690 695 700

gcc ggt tgc ggc ttc aac ccc tat ggc age ggc tac aaa age tac tac 2160Ala Gly Cys Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr705 710 715 720

ggc ccc gga gat acc gtt gac acc tcc aag acc ttc acc ate ate acc 2208

Gly Pro Gly Asp Thr Val Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr725 730 735

cag ttc aac acg gac aac ggc tcg ccc tcg ggc aac ctt gtg age ate 2256

Gln Phe Asn Thr Asp Asn Gly Ser Pro Ser Gly Asn .Leu Val Ser Ile740 745 750

acc cgc aag tac cag caa aac ggc gtc gac ate ccc age gcc cag ccc 2304

Thr Arg Lys Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro755 760 . 765

ggc ggc gac acc ate tcg tcc tgc ccg tcc gcc tca gcc tac ggc ggc 2352

Gly Gly Asp Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly770 775 780

ctc gcc acc atg ggc aag gcc ctg age age ggc atg gtg ctc gtg ttc- 2400Leu Ala Thr Met Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe785 790 795 800

age att tgg aac gac aac age cag tac atg aac tgg ctc gac age ggcSer Ile Trp Asn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly805 810 815aac gcc ggc ccc tgc age age acc gag ggc aac cca tcc aac ate ctg 2496

Asn Ala Gly Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu820 825 830

gcc aac aac ccc aac acg cac gtc gtc ttc tcc aac ate cgc tgg gga 2544

Ala Asn Asn Pro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly835 840 845

gac att ggg tet act acg aac tcg act gcg ccc ccg ccc ccg cct gcg 2592

Asp Ile Gly Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala850 855 860

tcc age acg acg ttt tcg act aca cgg agg age tcg acg act tcg age 2640

Ser Ser Thr Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser865 870 875 880

age ccg age 264 9

Ser Pro Ser

98

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<400> 98

Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

r Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

Thr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

Ser Gly Tyr Thr Thr Thr Thr Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

Asn Pro Tyr Pro. Pro Ala Asn Ala Ser Ser Cys Gly Ser Trp Ala Leu85 90 95

Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 445

o Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

Pro Pro Ala Thr Ala Val Glu. Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys485 490 495

Leu Thr Thr Tyr Lys Cys Thr Lys Ser Gly Gly Cys Val Ala Gln Asp500 505 510

"Thr Ser Val Val Leu Asp Trp Asn Tyr Arg Trp Met His Asp Ala Asn515 520 525

Asn Ser Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro530 535 540

Asp Glu Ala Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr545 550 555 560

Ala Ala Ser Gly Val Thr Thr Ser Gly Ser Ser Leu Thr Met Asn Gln565 570 575

Tyr Met Pro Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu580 585 590

Tyr Leu Leu Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly595 600 605Gln Glu Leu Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu610 615 620

Asn Gly Ser Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn625 630 635 640

Gln Tyr Asn Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala645 650 655

Gln Cys Pro Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His660 665 670

Gln Gly Phe Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg675 680 685

Asn Ala Leu Thr Pro His Ser Cys Thr' Ala Thr Ala Cys Asp Ser690 695 ' 700

Ala Gly Cys Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr705 710 715 720

Gly Pro Gly Asp Thr Val Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr725 730 735

Gln Phe Asn Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile740 745 750

Thr Arg Lys Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro755 760 765

m

y Gly Asp Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly770 775 780

Leu Ala Thr Met Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe785 790 795 800

Ser Ile Trp Asn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly805 810 - 815

Asn Ala Gly Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu820 825 830

Ala Asn Asn Pro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly835 840 845

Asp Ile Gly Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala850 855 860

Ser Ser Thr Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser865 870 875 880

Ser Pro Ser

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<400> 99

cag age age tgc gtc tcg gct tgg ggt caa tgt ggc ggt att tet tatGln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr

1 5 10 15

acc ggg tet acc tgc tgt cag agt ggg aat acc tgc gcc gag att aac

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

48

96

tcg tac tac tac cag tgc ata cca gea aca gct gtg agt act tca actSer Tyr Tyr Tyr Gln 'Cys Ile Pro Ala Thr Ala Val Ser Thr Ser Thr35 40 45

144

acc aca gtg aca tet ccc tet age tet ggt tcg tet tet gcc aac acg 192

^hr Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

tca ggt tat aca acg acg act gtc ttg ccc agt ccc acg gea aca cag 240

Ser Gly Tyr Thr Thr Thr Thr- Val Leu Pro Ser Pro Thr Ala Thr Gln65 70 75 80

aac cct tat cct ccg gcc aat gcc age tca tgt gga tcg tgg gct etcAsn Pro Tyr Pro Pro Ala Asn Ala Ser Ser Cys Gly Ser.Trp Ala Leu85 90 95

288

gtt gat aac gtt tgc tgc cca tac tac tgt etc tcg gat aat gaa tccVal Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

336

gag tcc tgc acg age age tgt acc ggc ggc tgc ggc agt cct gat tccGlu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Pro Asp Ser115 120 125

384

tcc atg tgc aag tcc ggg acg atg tgg gga gag caa cac acc gta actSer Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140

432tcc aac gag gac tgg cat tac age cgc tca aca cac ttt ggt ctg acc '480

Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

age ggt ggc gcc tgc ggg ttc ggt ctg tac ggc ctc tgc acc aag aac 528

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

agt gtc acc gcg age tgg aca gac cca atg ctg ggc tet acc tgc gac 576

Ser Val Thr Ala Ser Trp Thr Asp Pro Met Leu Gly Ser Thr Cys Asp180 185 190

gcc ttc tgc acc gcg tat ccg ctc ctc tgc aaa gac ccc gct aac gtc 624

Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

act ctc cgc ggg aac ttft gct gcc ccg aac gga gac tac tac act cag 672

Thr Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

ctgg cct tcc ctg gct gea tcc ggc aat ccc gac aac tac ctc tet 720

lRe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

tgc ggg gag tgt ttc gag gtc ate cgc acc aag ccc gac ggg aca gac 7 68

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 .255

tac gcc gtc ggc gag age gga tat acc gac ccc ata gtc ctc gag gta 816

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

gta gac age tgt ccc tgc aat gcc aat tca aaa tgg tgc tgt aag cgg 864

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

ccc ccc ccc ccc ccc ttt ttt tcc ccg cct tcc aac gga caa aat ctc 912

Pro Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

a aga cca ggc ggc. age ggc gea gac cac tgc ggc gaa ate gac ttc 960

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

aag tac ggc tgt cct ctg ccg gaa gga tcc cat cac atg gac ctc tcc 1008

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

gat att gcc atg ggc cga ctc cag gga aac ggc agt ctc gcc gac ggt 1056

Asp Ile Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

gtg att ccc ate cgc tac cgg cgt gtc ccc tgt ccc aag ccg ggg aac 1104

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

ate tac ate tgg -ctt cat gat ggg gcg gga ccg tat tat ttt gcg ctg 1152

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380

age gcg gtc aat acc aac ggc ccc ggc tcc gta ate agt ate gaa gtc 1200Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

cag gct ggt ggc tcc ggg cca tgg gtt gcc ctc gag cac gat ccg aac 1248

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp- Pro Asn405 410 415

tac acc agt age cgg ccg cag gag cgg tat ggc tet tgg gtc ctc ccg 1296

Tyr Thx Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

cag ggc aag gga ccc att act gtg cct gtt tcg atg agg ctg acg gcg 1344

Gln Gly Lys Gly Pro Ile Thr Val Pro Val Ser Met Arg Leu Thr Ala435 440 4 4 5

ccc aat ggg cag cag gtg gtt aag gag ggc gcc att acc age tat acc 1392

Pro Asn Gly Gln Gln Val Val Lys Glu Gly Ala Ile Thr Ser Tyr Thr450 455 460

[Some texts missing on original document] ccg gcg act gcg gtc gag ggc ttt tgg tat att gat ctg gga gtg 1440 [Some texts missing on original document] Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

cag ttc acc ggc tcg act tac tcc agt gga tet tet tcg ggg tcg ggg 1488

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser. Gly Ser Gly485 490 495

tet age tcc age tcg agt tcg act acc act aag gcc act tcg acg acc 1536

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

ttg aag act acc tcg acc acc age agt gga age agt tcg aca tcg gcg 1584 .

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

gcg cag caa ccg ggt acc age acc ccc gag gtc cat ccc aag ttg aca 1632

Ala Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys Leu Thr530 535 540

[Some texts missing on original document] tac aag tgt aca aag tcc ggg ggg tgc gtg gcc cag gac acc tcg 1680

[Some texts missing on original document] Tyr Lys Cys Thr Lys Ser Gly Gly Cys Val Ala Gln Asp Thr Ser545 550 555 560

gtg gtc ctt gac tgg aac tac cgc tgg atg cac gac gea aac tac aac 1728

Val Val Leu Asp Trp Asn Tyr Arg Trp Met His Asp Ala Asn Tyr Asn565 570 575

tcg tgc acc gtc aac ggc ggc gtc aac acc acg ctc tgc cct gac gag -1776Ser Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro Asp Glu580 585 590

gcg acc tgt ggc aag aac tgc ttc ate gag ggc gtc gac tac gcc gcc 1824

Ala Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala595 600 605

tcg ggc gtc acg acc tcg ggc age age ctc acc atg aac cag tac atg 1872

Ser Gly Val Thr Thr Ser Gly Ser Ser Leu Thr Met Asn Gln Tyr Met610 615 620

ccc age age tet ggc ggc tac age age gtc tet cct cgg ctg tat etc 1920Pro Ser Ser Ser. Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu625 630 635 640

ctg gac tct gac ggt gag tac gtg atg ctg aag ctc aac ggc cag gag 1968Leu Asp Ser Asp Gly Glu Tyr Val Met Leu Lys Leu Asn Gly Gln Glu645 650 655

ctg age ttc gac gtc gac ctc tct gct ctg ccg tgt gga gag aac ggc 2016

Leu Ser Phe Asp Val Asp Leu Ser Ala Leu Pro Cys Gly Glu Asn Gly660 665 670

tcg ctc- tac ctg tct cag atg gac gag aac ggg ggc gcc aac cag tat 2064

Ser Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr675 680 685

aac acg gcc ggt gcc aaç tac ggg age ggc tac tgc gat gct cag tgc 2112

Asn Thr Ala Gly Ala Asn Tyr Gly Ser Gly Tyr Cys Asp Ala Gln Cys690 695 700

ccc gtc cag aca tgg agg aac ggc acc ctc aac act age cac cag ggc 2160

Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His Gln Gly5 710 715 720

ttc tgc tgc aac gag atg gat ate ctg gag ggc aac tcg agg gcg aat 2208

Phe Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn725 730 735

gcc ttg acc cct cac tct tgc acg gcc acg gcc tgc gac tct gcc ggt 2256

Ala Leu Thr Pro His Ser Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly740 745 750

tgc ggc ttc aac ccc tat ggc age ggc tac aaa age tac tac ggc ccc 2304

Cys Gly Phe Asn Pro Tyr Gly Ser Gly Tyr Lys Ser Tyr Tyr Gly Pro755 760 765

gga gat acc gtt gac' acc tcc aag acc ttc acc ate ate acc cag ttc 2352

Gly Asp Thr Vai.Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr Gln Phe770 775 780

ac acg gac aac ggc tcg ccc tcg ggc aac ctt gtg age ate acc cgc 24 00

η Thr Asp Asn Gly Ser Pro Ser Gly Asn Leu Val Ser Ile Thr Arg5 790 795 800

aag tac cag caa aac ggc gtc gac ate ccc age gcc cag ccc ggc ggc 2448

Lys Tyr Gln Gln Asn Gly Val Asp Ile Pro Ser Ala Gln Pro Gly Gly805 810 815

gac acc ate tcg tcc tgc ccg tcc gcc tca gcc tac ggc ggc ctc gcc 24 96

Asp Thr Ile Ser Ser Cys Pro Ser Ala Ser Ala Tyr Gly Gly Leu Ala820 825 830

acc atg ggc aag gcc ctg age age ggc atg gtg ctc gtg ttc age att 2544

Thr Met Gly Lys Ala Leu Ser Ser Gly Met Val Leu Val Phe Ser Ile835 840 845

tgg aac gac aac age cag tac atg aac tgg ctc gac age ggc aac gcc 2592

Trp Asn Asp Asn Ser Gln Tyr Met Asn Trp Leu Asp Ser Gly Asn Ala850 855 860

ggc ccc tgc age age acc gag ggc aac cca tcc aac ate ctg gcc aac 2640

Gly Pro Cys Ser Ser Thr Glu Gly Asn Pro Ser Asn Ile Leu Ala Asn865 870 875 880aac ccc aac acg cac gtc gtc ttc tcc aac ate cgc tgg gga gac attAsn Pro Asn Thr His Val Val Phe Ser Asn Ile Arg Trp Gly Asp Ile885 890 895

2688

ggg tet act acg aac tcg act gcg ccc ccg ccc ccg cct gcg tcc ageGly Ser Thr Thr Asn Ser Thr Ala Pro Pro Pro Pro Pro Ala Ser Ser900 905 910

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acg acg ttt tcg act aca cgg agg age tcg acg act tcg age age ccgThr Thr Phe Ser Thr Thr Arg Arg Ser Ser Thr Thr Ser Ser Ser Pro915 920 925

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Gln Ser Ser Cys Val Ser Ala Trp Gly Gln Cys Gly Gly Ile Ser Tyr1 5 10 15

Thr Gly Ser Thr Cys Cys Gln Ser Gly Asn Thr Cys Ala Glu Ile Asn20 25 30

Ser Tyr Tyr Tyr Gln Cys Ile Pro Ala Thr Ala Val Ser Thr. Ser Thr

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Thr Val Thr Ser Pro Ser Ser Ser Gly Ser Ser Ser Ala Asn Thr50 55 60

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Val Asp Asn Val Cys Cys Pro Tyr Tyr Cys Leu Ser Asp Asn Glu Ser100 105 110

Glu Ser Cys Thr Ser Ser Cys Thr Gly Gly Cys Gly Ser Prò Asp Ser115 120 125

Ser Met Cys Lys Ser Gly Thr Met Trp Gly Glu Gln His Thr Val Thr130 135 140Ser Asn Glu Asp Trp His Tyr Ser Arg Ser Thr His Phe Gly Leu Thr145 150 155 160

Ser Gly Gly Ala Cys Gly Phe Gly Leu Tyr Gly Leu Cys Thr Lys Asn165 170 175

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Ala Phe Cys Thr Ala Tyr Pro Leu Leu Cys Lys Asp Pro Ala Asn Val195 200 205

Leu Arg Gly Asn Phe Ala Ala Pro Asn Gly Asp Tyr Tyr Thr Gln210 215 220

Phe Trp Pro Ser Leu Ala Ala Ser Gly Asn Pro Asp Asn Tyr Leu Ser225 230 235 240

Cys Gly Glu Cys Phe Glu Val Ile Arg Thr Lys Pro Asp Gly Thr Asp245 250 255

Tyr Ala Val Gly Glu Ser Gly Tyr Thr Asp Pro Ile Val Leu Glu Val260 265 270

Val Asp Ser Cys Pro Cys Asn Ala Asn Ser Lys Trp Cys Cys Lys Arg275 280 285

o Pro Pro Pro Pro Phe Phe Ser Pro Pro Ser Asn Gly Gln Asn Leu290 295 300

Thr Arg Pro Gly Gly Ser Gly Ala Asp His Cys Gly Glu Ile Asp Phe305 310 315 320

Lys Tyr Gly Cys Pro Leu Pro Glu Gly Ser His His Met Asp Leu Ser325 330 335

Asp lie Ala Met Gly Arg Leu Gln Gly Asn Gly Ser Leu Ala Asp Gly340 345 350

Val Ile Pro Ile Arg Tyr Arg Arg Val Pro Cys Pro Lys Pro Gly Asn355 360 365

Ile Tyr Ile Trp Leu His Asp Gly Ala Gly Pro Tyr Tyr Phe Ala Leu370 375 380Ser Ala Val Asn Thr Asn Gly Pro Gly Ser Val Ile Ser Ile Glu Val385 390 395 400

Gln Ala Gly Gly Ser Gly Pro Trp Val Ala Leu Glu His Asp Pro Asn405 410 415

Tyr Thr Ser Ser Arg Pro Gln Glu Arg Tyr Gly Ser Trp Val Leu Pro420 425 430

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Pro Pro Ala Thr Ala Val Glu Gly Phe Trp Tyr Ile Asp Leu Gly Val465 470 475 480

Gln Phe Thr Gly Ser Thr Tyr Ser Ser Gly Ser Ser Ser Gly Ser Gly485 490 495

Ser Ser Ser Ser Ser Ser Ser Thr Thr Thr Lys Ala Thr Ser Thr Thr500 505 510

Leu Lys Thr Thr Ser Thr Thr Ser Ser Gly Ser Ser Ser Thr Ser Ala515 520 525

Ala Gln Gln Pro Gly Thr Ser Thr Pro Glu Val His Pro Lys Leu Thr530 535 540

Thr Tyr Lys Cys Thr Lys Ser Gly Gly Cys Val Ala Gln Asp Thr Ser545 550 555 560

Val Val Leu Asp Trp Asn Tyr Arg Trp Met His Asp Ala Asn Tyr Asn565 570 575

Ser Cys Thr Val Asn Gly Gly Val Asn Thr Thr Leu Cys Pro Asp Glu580 585 590

Ala Thr Cys Gly Lys Asn Cys Phe Ile Glu Gly Val Asp Tyr Ala Ala595 600 605

Ser Gly Val Thr Thr Ser Gly Ser Ser Leu Thr Met Asn Gln Tyr Met610 615 620Pro Ser Ser Ser Gly Gly Tyr Ser Ser Val Ser Pro Arg Leu Tyr Leu625 630 635 640

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Ser Leu Tyr Leu Ser Gln Met Asp Glu Asn Gly Gly Ala Asn Gln Tyr675 680 685

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to Val Gln Thr Trp Arg Asn Gly Thr Leu Asn Thr Ser His Gln Gly705 710 715 720

Phe Cys Cys Asn Glu Met Asp Ile Leu Glu Gly Asn Ser Arg Ala Asn725 730 735

Ala Leu Thr Pro His Ser Cys Thr Ala Thr Ala Cys Asp Ser Ala Gly740 745 750

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Gly Asp Thr Val Asp Thr Ser Lys Thr Phe Thr Ile Ile Thr Gln Phe770 775 780

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Ser

<210> 101<211> 54<212> DNA<213> Trichoderma reesei

<220><221> CDS<222> (1)..(54)

<400> 101

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tct attSer Ile

<210> 102<211> 18<212> DNA<213> Trichoderma reesei

<400> 102

Met Ala Gly Lys Leu Ile Leu Val Ala Leu Ala Ser Leu Val Ser Leu1 5 10 15

Ser Ile

<210> 103<211> 51<212> DNA<213> Trichoderma reesei

Claims (29)

1. - Proteínas de fusão, caracterizadas porcompreender:- pelo menos uma swolenina, isto é, umaproteína contendo um domínio de molécula de ligação acarboidratos (CBM) que direciona para a celulose das plantas, eum domínio de expansina que decompõe as ligações dehidrogênio entre as microfibrilas da celulose,- e pelo menos uma enzima degradadora daparede celular de plantas, a referida enzima sendo de tal formaque ela contém um domínio CBM ou não, contanto que contenhauma CBM, o último pode ser deletado, se necessário,a referida swolenina e a enzima degradadora daparede celular de plantas sendo proteínas recombinantescorrespondendo a proteínas nativas em fungos, ou formasmutadas destes.

2. - Proteínas de fusão, de acordo com areivindicação 1, caracterizadas pelo fato de que a swoleninacorresponde a proteínas nativas, ou a formas mutadas destas, defungos escolhidos entre ascomicetes, tais como:Linhagens de Trichodermai e maisparticularmente Triehoderma reesei, oulinhagens de Aspergillus, e maisparticularmente Aspergillus fumigatus.

3. - Proteínas de fusão, de acordo com areivindicação 1 ou 2, caracterizadas pelo fato de que a swoleninacorresponde a enzimas nativas, ou suas formas mutadas, delinhagens de Trichoderma, tal como Trichoderma reesei.

4. Proteínas de fusão, de acordo com qualqueruma das reivindicações 1 a 3, caracterizadas pelo fato de que aswolenina é a proteína de Trichoderma reesei, representada pelaSEQ ID NO : 2 com seu peptídeo de sinal, ou pela SEQ ID NO :-4 em seu estado maduro.

5. Proteínas de fusão, de acordo com areivindicação 1 ou 2, caracterizadas pelo fato de que a swolenina% corresponde a enzimas nativas, ou suas formas mutadas, delinhagens de Aspergillus, tal como Aspergillus fumigatus.

6. Proteínas de fusão, de acordo com areivindicação 5, caracterizadas pelo fato de que a swolenina é aproteína de Aspergillus fumigatus, representada pela SEQ ID NO: 6 com seu peptídeo de sinal, ou pela SEQ ID NO : 8 em seuestado maduro.

7. Proteínas de fusão, de acordo com qualqueruma das reivindicações 1 a 6, caracterizadas pelo fato de que emque as enzimas degradadoras da parede celular de plantas sãoescolhidas entre enzimas capazes de hidrolizar a celulose, ahemicelulose e degradar a lignina.

8. Proteínas de fusão, de acordo com qualqueruma das reivindicações 1 a 7, caracterizadas pelo fato de que asenzimas degradadoras da parede celular de plantas são hidrolasesescolhidas entre:celulases, tais como endoglucanases,exoglucanases, tais como celobiohidrolases, ou β-glucosidases,- hemicelulases, tais como xilanases,- Iigninases capazes de degradar ligninas, taiscomo lacases, manganês peroxidases, lignina peroxidases,peroxidases versáteis ou enzimas suplementares, tais comocelobiose deidrogenases, e aril álcool oxidases,- cinamoil éster hidrolases capazes de liberarácidos cinâmicos, tais como ácidos ferúlicos e de hidrolizar% ligações cruzadas de ácido diferúlico entre cadeias dehemicelulose, tais como feruloil esterases, cinamoil esterases eácido clorogênico hidrolases.

9. - Proteínas de fusão, de acordo com qualqueruma das reivindicações 1 a 8, caracterizadas pelo fato de que asenzimas degradadoras da parede celular de plantas são escolhidasentre feruloil esterases, celobiohidrolases com ou sem seusdomínios CBM, endoglucanases com ou sem seus domínios® CBM, xilanases e lacases.

10. - Proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 9, caracterizadas pelo fato deque as enzimas degradadoras da parede celular de plantascorrespondem a enzimas nativas, ou a suas formas mutadas, defungos selecionados entre:* ascomicetes, tais como:- linhagens de Aspergillusi e maisparticularmente, Aspergillus niger,linhagens de Trichoderma, e maisparticularmente, Trichoderma reesei,Linhagens de Magnaporthe, e maisparticularmente, Magnaporthe grisea,* basidiomicetes, como linhagens dePycnoporus, Halocyphina ou Phanerochaetei e maisparticularmente, Pycnoporus cinnabarinus, Pycnoporussanguineus ou Halocyphina villosa, ou Phanerochaetechrysosporium.

11. - Proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 10, caracterizadas pelo fatode que as enzimas degradadoras da parede celular de plantascorrespondem a enzimas nativas, ou a suas formas mutadas, delinhagens de Aspergillus, tal como Aspergillus niger.

12. - Proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 11, caracterizadas pelo fatode que pelo menos uma das enzimas degradadoras da paredecelular de plantas é uma feruloil esterase, tal como a escolhidaentre:- a feruloil esterase A de A. niger, representadapela SEQ ID NO : 10, ou- a feruloil esterase B de A. niger representadapela SEQ ID NO : 12.

13. - Proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 11, caracterizadas pelo fatode que pelo menos uma das enzimas degradadoras da paredecelular de plantas é uma xilanase, tal como a xilanase B de A.niger, representada pela SEQ ID NO : 14.

14. Proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 10, caracterizadas pelo fatode que as enzimas degradadoras da parede celular de plantascorrespondem a enzimas nativas, ou a suas formas mutadas, delinhagens de Trichoderma, tal como Triehoderma reesei.

15. Proteínas de fusão, de acordo com areivindicação 14, caracterizadas pelo fato de que pelo menos umadas enzimas degradadoras da parede celular de plantas é umacelobiohidrolase, tal como a escolhida entre:- a celobiohidrolase I de T. reesei, erepresentada pela SEQ ID NO : 16,- a celobiohidrolase I de T. reesei, em que odomínio CBM foi deletado, e representada pela SEQ ID NO : 18,- a celobiohidrolase II de T. reesei, erepresentada pela SEQ ID NO : 20,- a celobiohidrolase II de T. reesei, em que odomínio CBM foi deletado, e representada pela SEQ ID NO : 22.

16. Proteínas de fusão, de acordo com areivindicação 14, caracterizadas pelo fato de que pelo menos umadas enzimas degradadoras da parede celular de plantas é umaendoglucanase, tal como a escolhida entre:- a endoglucanase I de T. reesei, e representadapela SEQ ID NO : 24,- a endoglucanase I de T. reesei, em que odomínio CBM foi deletado, e representada pela SEQ ID NO : 26.

17. Proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 16, caracterizadas porcompreender peptídeos de ligação entre pelo menos duas dasproteínas compreendidas nas referidas proteínas de fusão, osreferidos peptídeos de ligação sendo polipeptídeos de 10 a 100aminoácidos, de preferência de cerca de 50 aminoácidos.

18. Proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 17, caracterizadas pelo fatode que um peptídeo de ligação é incluído entre cada proteínacompreendida nas referidas proteínas de fusão.

19. Proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 18, caracterizadas pelo fatode que o peptídeo de ligação é um polipeptídeo hiperglicosilado,tal como a seqüência representada pela SEQ ID NO : 28, presentena celobiohidrolase B de A. niger.

20. Proteínas de fusão, de acordo com qualqueruma das reivindicações 1 a 19, caracterizadas por seremescolhidas entre as proteínas de fusão da swolenina deTrichoderma reesei representada pela SEQID NO : 4, com:- a feruloil esterase A de A. niger, representadapelo SEQ ID NO : 10, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 30,- a feruloil esterase A de A. niger, representadapela SEQ ID NO : 10, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 10, e sendo representada pela SEQ ID NO :-32,- a feruloil esterase B de A. niger, representadapela SEQ ID NO : 12, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 34,- a feruloil esterase B de A. niger, representadapela SEQ ID NO : 12, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 12, e sendo representada pela SEQ ID NO :-36,- a xilanase B de A. niger, representada pelaSEQ ID NO : 14, a referida proteína de fusão sendo representadapela SEQ ID NO : 38,- a xilanase B de A. niger, representada pelaSEQ ID NO : 14, a referida proteína de fusão compreendendo aseqüência representada pela SEQ ID NO : 28 como um peptídeode ligação hiperglicosilado entre a SEQ ID NO : 4 e a SEQ IDNO : 14, e sendo representada pela SEQ ID NO : 40,- a celobiohidrolase I de T. reesei representadapela SEQ ID NO : 16, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 42,- a celobiohidrolase I de T. reesei, representadapela SEQ ID NO : 16, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 16, e sendo representada pela SEQ ID NO :44,a celobiohidrolase I de T. reesei sem sua CBMendógena representada pela SEQ ID NO : 18, a referida proteínade fusão sendo representada pela SEQ ID NO : 46,a celobiohidrolase I de T. reesei, sem suaCBM endógena representada pela SEQ ID NO : 18, a referidaproteína de fusão compreendendo a seqüência representada pelaSEQ ID NO : 28 como um peptídeo de ligação hiperglicosiladoentre a SEQ ID NO : 4 e a SEQ ID NO : 18, e sendo representadapela SEQ ID NO : 48,a celobiohidrolase II de T. reesei pela SEQ IDNO : 20, a referida proteína de fusão sendo representada pelaSEQ ID NO : 50,a celobiohidrolase II de T. reesei, representadapela SEQ ID NO : 20, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 20, e sendo representada pela SEQ ID NO :52,a celobiohidrolase II de T. reesei sem suaCBM endógena representada pela SEQ ID NO : 22, a referidaproteína de fusão sendo representada pela SEQ ID NO : 54,- a celobiohidrolase II de T. reesei, sem suaCBM endógena representada pela SEQ ID NO : 22, a referidaproteína de fusão compreendendo a seqüência representada pelaSEQ ID NO : 28 como um peptídeo de ligação hiperglicosiladoentre a SEQ ID NO : 4 e a SEQ ID NO : 22, e sendo representadapela SEQ ID NO : 56,- a endoglucanase I de T. reesei representadapela SEQ ID NO : 24, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 58,- a endoglucanase I de T. reesei, representadapela SEQ ID NO : 24, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 4 e a SEQ ID NO : 24, e sendo representada pela SEQ ID NO :-60,- a endoglucanase I de T. reesei sem sua CBMendógena representada pela SEQ ID NO : 26, a referida proteínade fusão sendo representada pela SEQ ID NO : 62,- a endoglucanase I de T. reesei, sem sua CBMendógena representada pela SEQ ID NO : 26, a referida proteínade fusão compreendendo a seqüência representada pela SEQ IDNO : 28 como um peptídeo de ligação hiperglicosilado entre aSEQ ID NO : 4 e a SEQ ID NO : 26, e sendo representada pelaSEQ ID NO : 64.

21. - Proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 19, caracterizadas por seremescolhidas entre as proteínas de fusão da swolenina de Aspergillusfumigatus representada pela SEQ ID NO : 8, com:- a feruloil esterase A de A. niger, representadapelo SEQ ID NO : 10, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 66,- a feruloil esterase A de A. niger, representadapela SEQ ID NO : 10, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 10, e sendo representada pela SEQ ID NO :-68,- a feruloil esterase B de A. niger, representadapela SEQ ID NO : 12, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 70,- a feruloil esterase B de A. niger, representadapela SEQ ID NO : 12, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 12, e sendo representada pela SEQ ID NO :-72,- a xilanase B de A. niger, representada pelaSEQ ID NO : 14, a referida proteína de fusão sendo representadapela SEQ ID NO : 74,- a xilanase B de A. niger, representada pelaSEQ ID NO : 14, a referida proteína de fusão compreendendo aseqüência representada pela SEQ ID NO : 28 como um peptídeode ligação hiperglicosilado entre a SEQ ID NO : 8 e a SEQ IDNO : 14, e sendo representada pela SEQ ID NO : 76,- a celobiohidrolase I de T. reesei representadapela SEQ ID NO : 16, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 78,- a celobiohidrolase I de T. reesei, representadapela SEQ ID NO : 16, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 16, e sendo representada pela SEQ ID NO :-80,- a celobiohidrolase I de T. reesei sem sua CBMendógena representada pela SEQ ID NO : 18, a referida proteínade fusão sendo representada pela SEQ ID NO : 82,- a celobiohidrolase I de T. reesei, sem suaCBM endógena representada pela SEQ ID NO : 18, a referidaproteína de fusão compreendendo a seqüência representada pelaSEQ ID NO : 28 como um peptídeo de ligação hiperglicosiladoentre a SEQ ID NO : 8 e a SEQ ID NO : 18, e sendo representadapela SEQ ID NO : 84,- a celobiohidrolase II de T. reesei pela SEQ IDNO : 20, a referida proteína de fusão sendo representada pelaSEQ ID NO : 86,- a celobiohidrolase II de T. reesei, representadapela SEQ ID NO : 20, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 20, e sendo representada pela SEQ ID NO :-88,- a celobiohidrolase II de T. reesei sem suaCBM endógena representada pela SEQ ID NO : 22, a referidaproteína de fusão sendo representada pela SEQ ID NO : 90,- a celobiohidrolase II de T. reesei, sem suaCBM endógena representada pela SEQ ID NO : 22, a referidaproteína de fusão compreendendo a seqüência representada pelaSEQ ID NO : 28 como um peptídeo de ligação hiperglicosiladoentre a SEQ ID NO : 8 e a SEQ ID NO : 22, e sendo representadapela SEQ ID NO : 92,- a endoglucanase I de T. reesei representadapela SEQ ID NO : 24, a referida proteína de fusão sendorepresentada pela SEQ ID NO : 94,- a endoglucanase I de T. reesei, representadapela SEQ ID NO : 24, a referida proteína de fusãocompreendendo a seqüência representada pela SEQ ID NO : 28como um peptídeo de ligação hiperglicosilado entre a SEQ ID NO: 8 e a SEQ ID NO : 24, e sendo representada pela SEQ ID NO :-96,- a endoglucanase I de T. reesei sem sua CBMendógena representada pela SEQ ID NO : 26, a referida proteínade fusão sendo representada pela SEQID NO : 98,- a endoglucanase I de T. reesei, sem sua CBMendógena representada pela SEQ ID NO : 26, a referida proteínade fusão compreendendo a seqüência representada pela SEQ IDNO : 28 como um peptídeo de ligação hiperglicosilado entre aSEQ ID NO : 4 e a SEQ ID NO : 26, e sendo representada pelaSEQ IDNO : 100.

22. - Ácidos nucléicos, caracterizados porcodificarem uma proteína de fusão, conforme definida emqualquer uma das reivindicações 1 a 21.

23. - Vetores, caracterizados por seremtransformados com um ácido nucléico conforme definido nareivindicação 22.

24. - Células hospedeiras, caracterizadas porserem transformadas com um ácido nucléico conforme definidona reivindicação 22, usando um vetor conforme definido nareivindicação 23.

25. - Células hospedeiras transformadas, deacordo com a reivindicação 24, caracterizadas por seremescolhidas entre células de fungos, tais como os fungos definidosna reivindicação 10, e mais especificamente A. niger, A.fumigatus, Trichoderma reesei ou Pycnoporus cinnabarinus.

26. - Processo para a preparação de proteínas defusão, de acordo com a reivindicação 1 a 21, caracterizado porcompreender a cultura in vitro de células hospedeiras de acordocom a reivindicação 24 ou 25, a recuperação, e, se necessária, apurificação das proteínas de fusão produzidas pelas referidascélulas hospedeiras na cultura.

27. Uso de proteínas de fusão, de acordo comqualquer uma das reivindicações 1 a 21, caracterizado por ser pararealizar processos de degradação da parede celular de plantas noâmbito da preparação, a partir de plantas ou subprodutos vegetais,de compostos de interesse localizados na parede celular deplantas, ou no âmbito do branqueamento da polpa e do papel, paraa produção de biocombustíveis ou nas indústrias alimentícias.

28. Uso, de acordo com a reivindicação 27,caracterizado por ser para realizar processos de degradação deparede celular de plantas no âmbito da preparação dos seguintescompostos de interesse:- bioetanol,- antioxidantes, como ácido ferúlico ou ácidocaféico, que são ácidos cinâmicos, e hidroxitirosol, ou ácidogálico,aromas, como vanilina ou p-hidroxibenzaldeído, obtidos da biotransformação do ácidoferúlico ou do ácido p-coumárico, respectivamente.

29. Processo de degradação de parede celularde plantas no âmbito da preparação, a partir de plantas ousubprodutos vegetais, de compostos de interesse localizados naparede celular de plantas, caracterizado por compreender asseguintes etapas:- o tratamento enzimático de plantas ousubprodutos vegetais ou resíduos industriais, com proteínas defusão de acordo com qualquer uma das reivindicações 1 a 21, oucom células transformadas de acordo com a reivindicação 24 ou-25,- opcionalmente, o tratamento físico de plantasou subprodutos vegetais por explosão a vapor em combinaçãocom a ação de proteínas de fusão,- opcionalmente, a biotransformação commicroorganismos ou enzimas apropriados dos compostos contidosnas paredes celulares e liberados durante o tratamento enzimáticoanterior,- a recuperação, e se necessária, a purificação docomposto de interesse liberado pelas paredes celulares durante otratamento enzimático anterior ou obtido durante a etapa debiotransformação anterior.