Patent Application: US-32080002-A

Abstract:
a composition is provided comprising n . meningitidis outer membrane vesicles , wherein said outer membrane vesicles are enriched with at least one antigenic component . the composition is suitable for use in vaccines and for treatment of infection , particularly meningococcal infection , demonstrating a broad spectrum of protection . a number of preferred antigenic components are described and include antigenic proteins and proteoglycans derived from n . meningitidis .

Description:
mice ( camr - nih ) were immunised with tbps and / or outer membrane vesicles and challenged with either the homologous or a heterologous meningococcal strain . survivors per group of mice immunised with tbps from strain k454 and the outer membrane vesicle vaccine following challenge by strain k454 are shown in fig1 . compared to tbps , the outer membrane vesicle vaccine gave reduced protection but this may be because it is produced from a different group b strain ( h44 / 76 ). animals immunised with tbpa + b isolated from strain k454 were also protected against challenge with other serogroup b organisms ( fig1 ), with greater protection seen with the homologous strain and strains expressing a tbpb with a similar molecular weight . little or no protection was observed against challenge with meningococci possessing tbpb with a very different molecular weight ( strain b16b6 ). with the heterologous challenge strains , there is a slightly greater number survivors in the groups vaccinated with the combination of tbps + outer membrane vesicles . however , the numbers involved are small and no definite conclusions can be reached . it is interesting to observe that mice immunised with tbpa + b from strain k454 were also protected against infection with a serogroup c but not a serogroup a strain ( fig2 ). protection against challenge with strain k454 with mice immunised with co - purified tbpa + b and isolated tbpa and tbpb is shown in fig3 . it can be seen that tbpb is the predominant antigen responsible for protection , with little protection afforded by tbpa alone . tbpa and tbpb from n . meningitidis strain k454 were cloned and overexpressed in e . coli . the proteins were purified using affinity chromatography and used to determine their protective potency in a mouse model of meningococcal disease . recombinant tbps showed equivalent protection to that provided by tbps isolated from iron - stressed n . meningitidis ( fig4 a and 4b ). these recombinant tbps were also utilised in two further larger ip challenge experiments ( fig5 a - b ). the strong and consistent protective potency of tbps against mouse i . p . infection with n . meningitidis is probably the most compelling evidence for their vaccine potential . interestingly , the results shown in fig4 b and 5 a - b , although arising from experiments of similar design , show the surprising variability associated with vaccine compositions that depend solely upon either tbpa or tbpb alone . in fig4 b the recombinant tbpa composition displayed low levels of protection compared to tbpb or tbpa + b . however , in fig5 a and 5b the recombinant tbpa vaccine composition that showed high levels of protection comparable to the tbpa + b complex and the tbpb alone composition demonstrated poor protection to infection . this latter result is completely contrary to the teaching of the prior art . we have undertaken a number of studies looking at the antibody response in humans to tbpa and tbpb following meningococcal disease . the general conclusions are that both tbpa and tbpb are expressed during meningococcal disease and that an immune response is raised against them . the response is functional ( opsonic ) and is more cross - reactive between different meningococcal strains than is the response induced by immunisation of animals with tbps . the immune response to tbpa appears to be stronger and more cross - reactive than that to tbpb , confirming the importance of the vaccine potential of tbpa . our structural studies indicate that the transferrin receptor on the meningococcal surface consists of two tbpa molecules and one tbpb molecule that act together . we carried out further tests of the efficacy of recombinant tbpb versus recombinant tbpa + b containing vaccine formulations against challenge from n . meningitidis strains l91 705 and b16b6 , the results of which are illustrated in fig6 and 7 respectively . in both cases some improved protection was conferred by a + b compared to b alone . these methods can be used to enhance expression of tbpb but can equally be applied to other meningococcal outer membrane proteins with known sequence such as nspa ( martin et al ., 1997 ), omp85 ( manning et al ., 1998 ) or frpb ( pettersson et al ., 1995 ). any of the antigenic component sequences disclosed herein ( seq id nos : 1 ; 3 ; 5 ; 7 ; 9 ; 11 ; 13 ; 15 ; 17 ; 19 ; 21 ; 23 ; 25 ; 27 ; 29 ; 31 ; 33 ; 35 ; 37 ; 39 ; 41 ; 43 ; 45 ; 47 ; 49 ; 51 ; 53 ; 55 ; 57 ; 59 ; 61 ; 63 ; 65 ; 67 ; 69 ; and 71 ) would also be suitable for over expression in this system as would any immunogenic meningococcal sequence . in the following methods primers are designed using the primer select program from the ‘ dna star ’ software package ( www . dnastar . com ). primers to flanking sequences are designed following sequencing from the known coding region . up regulation of tbpb in n . meningitidis by promoter delivery using homologous recombination ( frosch et al ., 1990 , van der ley et al ., 1995 ) a strong promoter such as the pora promoter is inserted into the n . meningitidis genome upstream of the tbpb coding region ( legrain et al ., 1993 ). a selectable marker , encoding resistance to kanamycin , is also included in the delivery cassette upstream from the promoter . the integration locus is selected by sequencing upstream from the tbpb coding region . pcr primers are designed to the regions flanking the pora promoter and incorporate restriction endonuclease sites for ligation into this amplified sequence . this is then inserted into the multiple cloning site of a vector containing the kanamycin resistance gene . also inserted through pcr produced products are integration loci that complement a region directly before the coding region for tbpb in the n . meningitidis genome . through homologous recombination the construct shown in fig8 will be produced . from the published sequence of pora ( mcguinnes et al . 1990 ) ( seq id no : 1 ) a primer is constructed at the n - terminal region in order to sequence up steam of the coding region . this sequence data yields the promoter region of the highly expressed pora gene . primers are designed to this sequence so as to amplify any conserved hexamers centred around − 35 and − 10 the consensus sequences of ttgaca and tataat with a 16 - 18 bp gap between them and up to 67 bp upstream of the start of transcription ( atg ). the designed primers have restriction endonuclease sites incorporated in order to insert the amplified region into a suitable vector . in order to identify a suitable integration locus in front of the tbpb coding region a primer is designed to the start of the tbpb coding region , using the published sequence ( legrain et al . 1993 ), running up stream into the tbpb promoter region . the promoter region itself as well as some sequence upstream is suitable as the integration locus . this section is amplified in two halves using 4 primers and restriction endonucleases are incorporated in order to ligate the sections into a suitable vector . the vector used already contains an antibiotic resistance marker ( such as kanamycin ) and this is suitably positioned between the integration loci but upstream from the incorporated pora promoter , as illustrated in fig8 . this means that the vector used has cloning sites either side of the selectable marker . up regulation of tbpb in n . meningitidis by gene delivery a construct is produced containing a selectable marker , such as kanamycin resistance , up stream from a strong promoter ( pora ) which is in turn upstream from the coding region for tbpb . using homologous recombination ( frosch et al ., 1990 , van der ley et al ., 1995 ), the cassette is inserted into the n . meningitidis genome . the integration locus is selected by sequencing upstream from a known sequenced area that is also known to actively expressed . pcr is used to amplify the tbpb coding region and pora promoter region with suitable restriction endonucleases incorporated so they can be inserted in series , into a vector containing kanamycin resistance . also inserted into the construct are two flanking integration loci complementing a region of the n . meningitidis genome ( see fig9 ). from the published sequence of pora ( mcguinness et al . 1990 ) ( seq id no : 1 ) a primer can be constructed to complement the n - terminal region in order to sequence up steam of the coding region . this sequence data yields the promoter region of the highly expressed pora gene . primers are designed to this sequence so as to amplify any conserved hexamers centred around − 35 and − 10 the consensus sequences of ttgaca and tataat with a 16 - 18 bp gap between them and up to 67 bp upstream of the start of transcription ( atg ). the reverse primer is designed to be as close as possible to the start of the coding region , but does not actually include any of it . this ensures that when it is positioned in series with any inserted dna it acts as an efficient promoter . the designed primers have restriction endonuclease sites incorporated in order to insert the amplified region into a suitable vector . from the published sequence of tbpb ( legrain et al . 1993 ) primers are constructed to complement the c - terminal and n - terminal regions in order to sequence the flanking regions of the gene . from this sequence primers are constructed which amplify the entire gene . the forward primer incorporates the first coding triplet ( atg ) of the gene and does not include the full native promoter region . the reverse is as close to the end of the coding region as possible while still being a good partner to the forward primer . it is accepted that this means the reverse primer may be some distance downstream of the gene of interest . from the foregoing , it will be appreciated that although specific embodiments of the invention have been described herein for purposes of illustration , various modifications may be made without deviating from the spirit and scope of the invention . accordingly , the invention is not limited except as by the appended claims . atg cga aaa aaa ctt acc gcc ctc gta ttg tcc gca ctg ccg ctt gcg 48 gcc gtt gcc gat gtc agc cta tac ggc gaa atc aaa gcc ggc gtg gaa 96 ggc agg aac tac cag ctg caa ttg act gaa gca caa gcc gct aac ggt 144 gga gcg agc ggt cag gta aaa gtt act aaa gtt act aag gcc aaa agc 192 cgc atc agg acg aaa atc agt gat ttc ggc tcg ttt atc ggc ttt aag 240 ggg agt gag gat ttg ggc gac ggg ctg aag gct gtt tgg cag ctt gag 288 caa gac gta tcc gtt gcc ggc ggc ggc gcg acc cag tgg ggc aac agg 336 gaa tcc ttt atc ggc ttg gca ggc gaa ttc ggt acg ctg cgc gcc ggt 384 cgc gtt gcg aat cag ttt gac gat gcc agc caa gcc att gat cct tgg 432 arg val ala asn gln phe asp asp ala ser gln ala ile asp pro trp gac agc aat aat gat gtg gct tcg caa ttg ggt att ttc aaa cgc cac 480 asp ser asn asn asp val ala ser gln leu gly ile phe lys arg his gac gac atg ccg gtt tcc gta cgc tac gat tcc ccc gaa ttt tcc ggt 528 ttc agc ggc agc gtt caa ttc gtt ccg atc caa aac agc aag tcc gcc 576 tat acg ccg gct tat tat act aag aat aca aac aat aat ctt act ctc 624 gtt ccg gct gtt gtc ggc aag ccc gga tcg gat gtg tat tat gcc ggt 672 ctg aat tac aaa aat ggc ggt ttt gcc ggg aac tat gcc ttt aaa tat 720 gcg aga cac gcc aat gtc gga cgt aat gct ttt gag ttg ttc ttg atc 768 ggc agc ggg agt gat caa gcc aaa ggt acc gat ccc ttg aaa aac cat 816 gly ser gly ser asp gln ala lys gly thr asp pro leu lys asn his cag gta cac cgt ctg acg ggc ggc tat gag gaa ggc ggc ttg aat ctc 864 gcc ttg gcg gct cag ttg gat ttg tct gaa aat ggc gac aaa acc aaa 912 aac agt acg acc gaa att gcc gcc act gct tcc tac cgc ttc ggt aat 960 gca gtt cca cgc atc agc tat gcc cat ggt ttc gac ttt atc gaa cgc 1008 ala val pro arg ile ser tyr ala his gly phe asp phe ile glu arg ggt aaa aaa ggc gaa aat acc agc tac gat caa atc atc gcc ggc gtt 1056 gly lys lys gly glu asn thr ser tyr asp gln ile ile ala gly val gat tat gat ttt tcc aaa cgc act tcc gcc atc gtg tct ggc gct tgg 1104 asp tyr asp phe ser lys arg thr ser ala ile val ser gly ala trp ctg aaa cgc aat acc ggc atc ggc aac tac act caa att aat gcc gcc 1152 arg val ala asn gln phe asp asp ala ser gln ala ile asp pro trp asp ser asn asn asp val ala ser gln leu gly ile phe lys arg his gly ser gly ser asp gln ala lys gly thr asp pro leu lys asn his ala val pro arg ile ser tyr ala his gly phe asp phe ile glu arg gly lys lys gly glu asn thr ser tyr asp gln ile ile ala gly val asp tyr asp phe ser lys arg thr ser ala ile val ser gly ala trp atg aaa aaa gca ctt gcc aca ctg att gcc ctc gct ctc ccg gcc gcc 48 gca ctg gcg gaa ggc gca tcc ggc ttt tac gtc caa gcc gat gcc gca 96 cac gca aaa gcc tca agc tct tta ggt tct gcc aaa ggc ttc agc ccg 144 cgc atc tcc gca ggc tac cgc atc aac gac ctc cgc ttc gcc gtc gat 192 arg ile ser ala gly tyr arg ile asn asp leu arg phe ala val asp tac acg cgc tac aaa aac tat aaa gcc cca tcc acc gat ttc aaa ctt 240 tyr thr arg tyr lys asn tyr lys ala pro ser thr asp phe lys leu tac agc atc ggc gcg tcc gcc att tac gac ttc gac acc caa tcg ccc 288 gtc aaa ccg tat ctc ggc gcg cgc ttg agc ctc aac cgc gcc tcc gtc 336 gac ttg ggc ggc agc gac agc ttc agc caa acc tcc atc ggc ctc ggc 384 gta ttg acg ggc gta agc tat gcc gtt acc ccg aat gtc gat ttg gat 432 gcc ggc tac cgc tac aac tac atc ggc aaa gtc aac act gtc aaa aac 480 gtc cgt tcc ggc gaa ctg tcc gcc ggt gtg cgc gtc aaa ttc 522 arg ile ser ala gly tyr arg ile asn asp leu arg phe ala val asp tyr thr arg tyr lys asn tyr lys ala pro ser thr asp phe lys leu atg aaa ctg aaa cag att gct tcc gca ctg atg atg ttg ggc ata tcg 48 cct ttg gca ctt gcc gac ttc acc atc caa gac atc cgc gtc gaa ggc 96 pro leu ala leu ala asp phe thr ile gln asp ile arg val glu gly ttg cag cgt acc gag ccg agt acc gta ttc aac tac ctg ccc gtc aaa 144 leu gln arg thr glu pro ser thr val phe asn tyr leu pro val lys gtc ggc gac acc tac aac gac aca cac ggc agt gcc atc atc aaa agc 192 val gly asp thr tyr asn asp thr his gly ser ala ile ile lys ser ctg tac gcc acc ggt ttc ttt gac gac gta cgc gtc gaa act gcg gac 240 ggg cag ctc ctg ctg acc gtt atc gaa cgc ccc acc atc ggc tcg ctc 288 aac atc acc ggc gca aaa atg ctg caa aac gac gcc att aag aaa aac 336 ctc gaa tcg ttc ggg ctg gcg cag tcg caa tac ttt aat cag gcg aca 384 ctc aat cag gca gtc gcc ggc ctg aaa gaa gaa tac ctc ggg cgc ggc 432 aaa ctc aat atc caa atc acg ccc aaa gta acc aaa ctc gcc cgc aac 480 cgc gtc gac atc gac atc acg att gac gag ggc aaa tcc gcc aaa atc 528 acc gac atc gaa ttt gaa ggc aac caa gtc tat tcc gac cgc aaa ctg 576 thr asp ile glu phe glu gly asn gln val tyr ser asp arg lys leu atg cgg caa atg tcc ctg acc gaa ggc ggc att tgg aca tgg ctg aca 624 cga agc aac caa ttc aac gag cag aaa ttt gcc caa gat atg gaa aaa 672 gta acc gac ttc tac caa aat aac ggc tac ttc gat ttc cgt atc ctc 720 val thr asp phe tyr gln asn asn gly tyr phe asp phe arg ile leu gat acc gac atc caa acc aac gaa gac aaa acc aag cag acc atc aaa 768 atc acc gtc cac gaa ggc gga cgt ttc cgt tgg ggc aaa gtc tcc atc 816 ile thr val his glu gly gly arg phe arg trp gly lys val ser ile gaa ggc gac acc aac gaa gtc ccc aaa gcc gaa ctg gaa aaa ctg ctg 864 acc atg aag ccc ggc aaa tgg tac gaa cgc cag cag atg acc gcc gtt 912 thr met lys pro gly lys trp tyr glu arg gln gln met thr ala val ttg ggt gag att cag aac cgc atg ggc tcg gca ggc tac gca tac agc 960 leu gly glu ile gln asn arg met gly ser ala gly tyr ala tyr ser gaa atc agc gta cag ccg ctg ccg aac gct gaa acc aaa acc gtc gat 1008 glu ile ser val gln pro leu pro asn ala glu thr lys thr val asp ttc gtc ctg cac atc gaa ccg ggc cgg aaa atc tac gtc aac gaa ata 1056 phe val leu his ile glu pro gly arg lys ile tyr val asn glu ile cac atc acc ggc aac aac aaa acc cgc gac gaa gtc gtc cgc cgt gaa 1104 tta cgc caa atg gaa tcc gca cct tac gac acc tcc aag ctg caa cgt 1152 leu arg gln met glu ser ala pro tyr asp thr ser lys leu gln arg tcc aaa gag cgc gtc gag ctt ttg ggc tac ttc gac aat gtc cag ttt 1200 ser lys glu arg val glu leu leu gly tyr phe asp asn val gln phe gat gct gtc ccg ctt gcc ggc acg ccc gac aaa gtc gat ttg aac atg 1248 agt ctg acc gaa cgt tcc acc ggt tcc ctg gat ttg agc gcg ggt tgg 1296 gtt caa gat acc ggg ttg gtc atg tcc gca ggc gtt tcc caa gac aac 1344 ctg ttc ggt acg ggc aag tcg gcc gca ctg cgc gcc tcc agg agc aaa 1392 acc acg ctt aac ggc tcg ctg tcg ttt act gac ccg tac ttc acg gca 1440 gac ggg gtc agc ctg ggc tac gat gtt tac gga aaa gcc ttc gac ccg 1488 cgc aaa gca tcg acc agc atc aaa caa tat aaa acc acc acg gca ggc 1536 gca ggc atc cgc atg agc gtg cct gtt acc gaa tac gac cgc gtg aat 1584 ala gly ile arg met ser val pro val thr glu tyr asp arg val asn ttc ggt ttg gtg gca gaa cac ctg acc gtc aac acc tac aac aaa gcg 1632 phe gly leu val ala glu his leu thr val asn thr tyr asn lys ala ccc aaa cac tat gcc gac ttt atc aag aaa tac ggc aaa acc gac ggc 1680 aca gac ggc agc ttc aaa ggc tgg ctg tac aaa ggt acc gtc ggc tgg 1728 ggg cgc aac aaa acc gac agc gcg tta tgg ccg acg cgc ggc tac ctg 1776 gly arg asn lys thr asp ser ala leu trp pro thr arg gly tyr leu acg ggc gtg aac gcc gaa atc gcc ctg cct ggc agc aaa ctg caa tac 1824 thr gly val asn ala glu ile ala leu pro gly ser lys leu gln tyr tac tcc gcc acc cac aac caa acc tgg ttc ttc ccc ctg agc aaa acc 1872 tyr ser ala thr his asn gln thr trp phe phe pro leu ser lys thr ttc acg ctg atg ctc ggc ggc gaa gtc ggc att gcg ggc ggc tac ggc 1920 aga acc aaa gaa atc ccc ttc ttt gaa aac ttc tac ggc ggc ggc ctg 1968 arg thr lys glu ile pro phe phe glu asn phe tyr gly gly gly leu ggt tcg gtg cgc gga tac gaa agc ggc acg ctc ggt ccg aaa gtc tat 2016 gac gaa tac ggc gaa aaa atc agc tac ggc ggc aac aaa aaa gcc aac 2064 gtc tcc gcc gag ctg ctc ttc ccg atg ccc ggc gcg aaa gac gcg cgc 2112 val ser ala glu leu leu phe pro met pro gly ala lys asp ala arg acc gtc cgc ctg agc ctg ttt gcc gac gca ggc agc gtg tgg gac ggc 2160 aaa acc tac gac gac aac agc agt tcc gcg acc ggc ggc agg gtt caa 2208 lys thr tyr asp asp asn ser ser ser ala thr gly gly arg val gln aac att tac ggc gcc ggc aat acc cat aaa tcc acc ttt acc aac gaa 2256 asn ile tyr gly ala gly asn thr his lys ser thr phe thr asn glu ttg cgc tat tcc gcc ggc ggc gcg gtt acc tgg ctc tcg cct tta ggc 2304 ccg atg aaa ttc agc tac gcc tac ccg ctg aag aaa aaa ccg gaa gac 2352 pro leu ala leu ala asp phe thr ile gln asp ile arg val glu gly leu gln arg thr glu pro ser thr val phe asn tyr leu pro val lys val gly asp thr tyr asn asp thr his gly ser ala ile ile lys ser thr asp ile glu phe glu gly asn gln val tyr ser asp arg lys leu val thr asp phe tyr gln asn asn gly tyr phe asp phe arg ile leu ile thr val his glu gly gly arg phe arg trp gly lys val ser ile thr met lys pro gly lys trp tyr glu arg gln gln met thr ala val leu gly glu ile gln asn arg met gly ser ala gly tyr ala tyr ser glu ile ser val gln pro leu pro asn ala glu thr lys thr val asp phe val leu his ile glu pro gly arg lys ile tyr val asn glu ile leu arg gln met glu ser ala pro tyr asp thr ser lys leu gln arg ser lys glu arg val glu leu leu gly tyr phe asp asn val gln phe ala gly ile arg met ser val pro val thr glu tyr asp arg val asn phe gly leu val ala glu his leu thr val asn thr tyr asn lys ala gly arg asn lys thr asp ser ala leu trp pro thr arg gly tyr leu thr gly val asn ala glu ile ala leu pro gly ser lys leu gln tyr tyr ser ala thr his asn gln thr trp phe phe pro leu ser lys thr arg thr lys glu ile pro phe phe glu asn phe tyr gly gly gly leu val ser ala glu leu leu phe pro met pro gly ala lys asp ala arg lys thr tyr asp asp asn ser ser ser ala thr gly gly arg val gln asn ile tyr gly ala gly asn thr his lys ser thr phe thr asn glu atg aat acc cca ttg ttc cgt ctc agc ctg ctc tcg ctt acc ctg gcg 48 gca ggt ttt gcc cat gcg gca gaa aat aat gcc aag gtc gta ctg gat 96 acc gtt acc gta aaa ggc gac cgc caa ggc agc aaa atc cgt acc aac 144 atc gtt acg ctg caa caa aaa gac gaa agc acc gca acc gat atg cgc 192 ile val thr leu gln gln lys asp glu ser thr ala thr asp met arg gaa ctc tta aaa gaa gag ccc tcc atc gat ttc ggc ggc ggc aac ggc 240 acg tcc caa ttc ctg acg ctg cgc ggc atg ggt caa aac tct gtc gac 288 thr ser gln phe leu thr leu arg gly met gly gln asn ser val asp atc aag gtg gac aac gcc tat tcc gac agc caa atc ctt tac cac caa 336 ile lys val asp asn ala tyr ser asp ser gln ile leu tyr his gln ggc aga ttt att gtc gat ccc gct ttg gtt aaa gtc gtt tcc gta caa 384 gly arg phe ile val asp pro ala leu val lys val val ser val gln aaa ggc gcg ggt tcc gcc tct gcc ggt atc ggc gcg acc aac ggc gcg 432 atc atc acc aaa acc gtc gat gcc caa gac ctg ctc aaa ggc ttg gat 480 aaa aac tgg ggc gtg cgc ctc aac agc ggc ttt gcc agc aac gaa ggc 528 lys asn trp gly val arg leu asn ser gly phe ala ser asn glu gly gta agc tac ggc gca agc gta ttc ggg aaa gag ggc aac ttc gac ggc 576 ttg ttc tct tac aac cgc aac aat gaa aaa gat tac gaa gca ggt aaa 624 leu phe ser tyr asn arg asn asn glu lys asp tyr glu ala gly lys ggc ttc cgt aat aat ttc aac ggc ggc aaa acc gta ccg tac agc gcg 672 gly phe arg asn asn phe asn gly gly lys thr val pro tyr ser ala ctg gac aaa cgc agc tac ctc gcc aaa atc gga aca agc ttc ggc gac 720 leu asp lys arg ser tyr leu ala lys ile gly thr ser phe gly asp ggc gac cac cgc atc gta ttg agc cat atg aaa gac cag cac cgg ggc 768 gly asp his arg ile val leu ser his met lys asp gln his arg gly atc cgt acc gtc cgt gaa gaa ttt acc gtc ggc ggc gat aaa gag cga 816 ata agt atg gaa cgc caa gcc cct gct tac cgc gaa acc aca caa tcc 864 aac acc aat ttg gcg tac acg ggt aaa aac ctg ggc ttt gtc gaa aaa 912 ctg gat gcc aac gcc tat gtg ttg gaa aaa gaa cgc tat tcc gcc gat 960 gac agc ggc acc ggt tac gca ggc aat gta aaa ggc ccc aac cat acc 1008 asp ser gly thr gly tyr ala gly asn val lys gly pro asn his thr caa atc acc act cgg ggt atg aac ttc aac ttc gac agc cgc ctt gcc 1056 gln ile thr thr arg gly met asn phe asn phe asp ser arg leu ala gaa caa acc ctg ctg aaa tac ggt atc aac tac cgc cat cag gaa atc 1104 glu gln thr leu leu lys tyr gly ile asn tyr arg his gln glu ile aaa ccg caa gcg ttt ttg aat tca caa ttt aaa att gaa gat aaa gaa 1152 lys pro gln ala phe leu asn ser gln phe lys ile glu asp lys glu aaa gca act gat gaa gag aaa aat aag aac cgt gaa aat gaa aaa att 1200 gcc aaa gcc tac cgt ctg acc aac ccg acc aaa acc gat acc ggc gcg 1248 tat atc gaa gcc att cac gag att gac ggc ttt acc ctg acc ggc ggg 1296 ctg cgt tac gac cgc ttc aag gtg aaa acc cac gac ggc aaa acc gtt 1344 tca agc aac aac ctt aac ccg agt ttc ggc gtg att tgg cag ccg cac 1392 ser ser asn asn leu asn pro ser phe gly val ile trp gln pro his gaa cac tgg agc ttc agc gcg agc cac aac tac gcc agc cgc agc ccg 1440 cgc ctg tat gac gcg ctg caa acc cac ggc aaa cgc ggc atc atc tcg 1488 arg leu tyr asp ala leu gln thr his gly lys arg gly ile ile ser att gcc gac ggc acg aaa gcc gaa cgc gcg cgc aat acc gaa atc ggc 1536 ttc aac tac aac gac ggc acg ttt gcc gca aac ggc agc tac ttc tgg 1584 cag acc atc aaa gac gcg ctt gcc aat ccg caa aac cgc cac gac tct 1632 gln thr ile lys asp ala leu ala asn pro gln asn arg his asp ser gtc gcc gtc cgt gaa gcc gtc aat gcc ggt tac atc aaa aac cac ggt 1680 tac gaa ttg ggc gcg tcc tac cgc acc ggc ggc ctg act gcc aaa gtc 1728 ggc gta agc cac agc aaa ccg cgc ttt tac gat acg cac aaa gac aag 1776 gly val ser his ser lys pro arg phe tyr asp thr his lys asp lys ctg ttg agc gcg aat cct gaa ttt ggc gca caa gtc ggc cgc act tgg 1824 leu leu ser ala asn pro glu phe gly ala gln val gly arg thr trp acg gct tcc ctt gcc tac cgc ttc caa aac ccg aat ctg gaa atc ggc 1872 thr ala ser leu ala tyr arg phe gln asn pro asn leu glu ile gly tgg cgc ggc cgt tat gtt caa aaa gcc gtg ggt tcg ata ttg gtg gca 1920 trp arg gly arg tyr val gln lys ala val gly ser ile leu val ala ggt caa aaa gac cgc aac ggc aaa ttg gaa aac gtt gta cgc aaa ggt 1968 ttc ggt gtg aac gat gtc ttc gcc aac tgg aaa ccg ctg ggc aaa gac 2016 acg ctc aat gtt aat ctt tcg gtt aac aac gtg ttc aac acg ttc tac 2064 tat ccg cac agc caa cga tgg acc aat acc ctg ccg ggc gtg gga cgt 2112 tyr pro his ser gln arg trp thr asn thr leu pro gly val gly arg gat gta cgc ttg ggc gtg aac tac aag ttc 2142 ile val thr leu gln gln lys asp glu ser thr ala thr asp met arg thr ser gln phe leu thr leu arg gly met gly gln asn ser val asp ile lys val asp asn ala tyr ser asp ser gln ile leu tyr his gln gly arg phe ile val asp pro ala leu val lys val val ser val gln lys asn trp gly val arg leu asn ser gly phe ala ser asn glu gly leu phe ser tyr asn arg asn asn glu lys asp tyr glu ala gly lys gly phe arg asn asn phe asn gly gly lys thr val pro tyr ser ala leu asp lys arg ser tyr leu ala lys ile gly thr ser phe gly asp gly asp his arg ile val leu ser his met lys asp gln his arg gly asp ser gly thr gly tyr ala gly asn val lys gly pro asn his thr gln ile thr thr arg gly met asn phe asn phe asp ser arg leu ala glu gln thr leu leu lys tyr gly ile asn tyr arg his gln glu ile lys pro gln ala phe leu asn ser gln phe lys ile glu asp lys glu ser ser asn asn leu asn pro ser phe gly val ile trp gln pro his arg leu tyr asp ala leu gln thr his gly lys arg gly ile ile ser gln thr ile lys asp ala leu ala asn pro gln 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288 glu tyr ala asp pro leu leu ser lys ile ser ala ala gln asn ser agc cgt gcg cgt ctg gtt ctg aat ctg aac aaa ccg ggc caa tac aat 336 ser arg ala arg leu val leu asn leu asn lys pro gly gln tyr asn acc gaa gta cgc ggg aac aaa gtt tgg ata ttc att aac gaa tcg gac 384 thr glu val arg gly asn lys val trp ile phe ile asn glu ser asp gat acc gtg tcc gcc ccc gca cgc ccc gcc gta aaa gcc gcg cct gcc 432 gca ccg gca aaa caa cag gct gcc gca ccg tct acc aag tcc gca gta 480 tcc gta tcc gaa ccc ttt acc ccg gca aaa caa cag gct gcc gca ccg 528 ttt acc gag tcc gta gta tcc gta tcc gca ccg ttc agc ccg gca aaa 576 caa acc aat atc gat ttc cgc aaa gac ggc aaa aat gcc ggc att atc 720 gaa ttg gct gca ttg ggc ttt gcc ggg cag ccc gac atc agc caa cag 768 cac gac cac atc atc gtt acg ctg aaa aac cat acc ctg ccg acc acg 816 ctc caa cgc agt ttg gat gtg gca gac ttt aaa aca ccg gtt caa aag 864 leu gln arg ser leu asp val ala asp phe lys thr pro val gln lys gtt acg ctg aaa cgc ctc aat aac gac acc cag ctg att atc aca 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acc gta acc tca atc gcg aac 1920 ile glu ser gly tyr glu ile pro phe thr val thr ser ile ala asn ggc ggc agc agc acg aac acg gaa ctc aaa aaa gcc gtc ttg ggg ctg 1968 acc gtt acg ccg aac atc acg ccc gac ggc caa atc att atg acc gtc 2016 aaa atc aac aag gac tcg cct gcg caa tgt gcc tcc ggt aat cag acg 2064 lys ile asn lys asp ser pro ala gln cys ala ser gly asn gln thr atc ctg tgt att tcg acc aaa aac ctg aat acg cag gct atg gtt gaa 2112 ile leu cys ile ser thr lys asn leu asn thr gln ala met val glu aac ggc ggc aca ttg att gtc ggc ggt att tat gaa gaa gac aac ggc 2160 aat acg ctg acc aaa gtc ccc ctg ttg ggc gac atc ccc gtt atc ggc 2208 aac ctc ttt aaa aca cgc ggg aaa aaa acc gac cgc cgc gaa ctg ctg 2256 att ttc att acc ccg agg att atg ggt acg gcc ggc aac agc ctg cgc 2304 ile phe ile thr pro arg ile met gly thr ala gly asn ser leu arg met asn thr lys leu thr lys ile ile ser gly leu phe val ala thr ala ala phe gln thr ala ser ala gly asn ile thr asp ile lys val glu ile val asn pro thr gly phe val thr ser ser pro ala arg ile ala leu asp phe glu gln thr gly ile ser met asp gln gln val leu glu tyr ala asp pro leu leu ser lys ile ser ala ala gln asn ser ser arg ala arg leu val leu asn leu asn lys pro gly gln tyr asn thr glu val arg gly asn lys val trp ile phe ile asn glu ser asp leu gln arg ser leu asp val ala asp phe lys thr pro val gln lys ala gly asn trp glu leu val asn lys ser ala ala pro gly tyr phe thr phe gln val leu pro lys lys gln asn leu glu ser gly gly val asn asn ala pro lys thr phe thr gly arg lys ile ser leu asp phe gln asp val glu ile arg thr ile leu gln ile leu ala lys glu ser gly met asn ile val ala ser asp ser val asn gly lys met thr leu lys asp ile ala asp leu gly ala leu tyr ser gln asn phe gln leu lys tyr lys asn val glu glu phe arg ser ile leu arg leu asp asn leu lys asn asp thr ser ala phe gly trp gly val asn ser gly phe gly gly asp asp lys trp gly ala glu thr lys ile asn leu pro ile ile glu ser gly tyr glu ile pro phe thr val thr ser ile ala asn lys ile 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met met ala ile gly ggc ggc act tat cgc ggc gaa gcc ggt tac gcc atc ggc tac tcc agt 1680 att tcc gac ggc gga aat tgg att atc aaa ggc acg gct tcc ggc aat 1728 tcg cgc ggc cat ttc ggt gct tcc gca tct gtc ggt tat cag tgg 1773 val gln arg thr val ala val leu ile val asn ser asp lys glu gly thr gly glu lys glu lys val glu glu asn ser asp trp ala val tyr phe asn glu lys gly val leu thr ala arg glu ile thr leu lys ala gly asp asn leu lys ile lys gln asn gly thr asn phe thr tyr ser ile lys gly val lys pro gly thr thr ala ser asp asn val asp phe val arg thr tyr asp thr val glu phe leu ser ala asp thr lys thr asn gly lys asn ile asp ile ala thr ser met thr pro gln phe ser gly leu val gln ala tyr leu pro gly lys ser met met ala ile gly atg aaa gtt ttg aac ggt tgg tcg gac agg aag atg tgg cgg gtt ttg 48 agt gct ttg ccg ata ggc gtg gtg ttt ttt gat ttg atc tac ggt ttt 96 gtg ttg aat gtg ttg cag ggt ttg gat ttg cag cgt gcc gtg ccg gat 144 tcg gaa ggc gtg ttg gcg gtt acg ccc gat att gca ttc aac agt ttg 192 ser glu gly val leu ala val thr pro asp ile ala phe asn ser leu cag att gtc gcc aac ggc ggt atg gcg gcg gtg gtc tgt ttc ggg ttg 240 gcg gtt gtg ttt ttg ctc aac cgt tcg gtg cgg cgg cgg cag gtg ttg 288 gaa atc ggg gtg ttc cgg atg ttg ggg ctg gtg gcg gta ttg gcg ttc 336 agc gcg ccg tcg gtg tgg gag tgg gcg aac gcg ctg ccg ctg ctg ctg 384 aag ggc gcg gac gtg gtc aat acg ggg aat gcg cgt tat gtg ctg acg 432 gct ttg tgt atg ccc ttt cct gcg gtg tcg tgc gtc atc ggg ctg gtg 480 ggg cgg ttc agg ctt cag acg gca tcg ggc agg gcg gca aag tca ggg 528 ser glu gly val leu ala val thr pro asp ile ala phe asn ser leu atg aat aaa aat att aaa tct tta aat tta cgg gaa aaa gac ccg ttt 48 met asn lys asn ile lys ser leu asn leu arg glu lys asp pro phe tta agt cgt gaa aaa cag cgt tat gaa cat cct ttg ccc agt cgg gaa 96 tgg ata atc gag ctg ctt gaa cgt aaa ggc gta cca tcc aag att gaa 144 gct ttg gta cgc gaa ttg tcg att aag gaa gaa gag tac gaa ttt ttc 192 gaa cgt cgt ctg aag gcg atg gcg cgg gac ggt cag gtt tta 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atc 672 gaa gtt ttg ggc gat tat gcc gac agc ggc atg gag att gaa att gcc 720 gtg cgc aag cat cat ttg ccg cac caa ttc agt gaa gcg tgt gcc aaa 768 val arg lys his his leu pro his gln phe ser glu ala cys ala lys gcc gcg aaa aaa att ccc gac cat gta cgc aaa agc gat ttg aaa ggc 816 ala ala lys lys ile pro asp his val arg lys ser asp leu lys gly cgc gtc gat ttg cgc gac ctg cct ttg gta acg ata gac ggc gaa acg 864 gct cga gat ttt gac gat gcg gtg ttt gcc gag aaa atc gga cgc aat 912 tac cgt ctg gtc gtg gcg att gcc gat gtc agc cat tat gtc cgc ccc 960 gat gac gct atc gac acg gac gct cag gaa cgc agc acc agt gtt tac 1008 ttc ccg cgc cgc gtg att ccc atg ttg ccg gaa aac ctg tcc aac ggc 1056 phe pro arg arg val ile pro met leu pro glu asn leu ser asn gly atc tgc tcg ctc aat cct cat gtc gag cgt ttg tgt gtg gtg tgc gat 1104 ile cys ser leu asn pro his val glu arg leu cys val val cys asp atg gtt atc act tac gcg ggc aat atc aaa gaa tac cgc ttc tac ccc 1152 met val ile thr tyr ala gly asn ile lys glu tyr arg phe tyr pro gcc gtg atg cgc tct cat gcc cgc ctg acc tac aac caa gtt tgg aaa 1200 ala val met arg ser his ala arg leu thr tyr asn gln val trp lys tgg ctt tca ggc ggc atc gag cat ccg ttc aaa acc caa atc gac acg 1248 trp leu ser gly gly ile glu his pro phe lys thr gln ile asp thr ctt tac aaa ctc ttc aaa atc ctt cag aaa aag cgt ttc gaa cgc ggg 1296 gcg gtg gag ttt gac agc atc gaa acc caa atg ctt ttc gac gac aac 1344 ala val glu phe asp ser ile glu thr gln met leu phe asp asp asn ggt aaa att gaa aaa atc gtc ccc gtt gtc cgc aac gat gcc cac aag 1392 gly lys ile glu lys ile val pro val val arg asn asp ala his lys ctg att gaa gaa tgt atg ttg gcg gca aac gtt tgc gca gcg gat ttt 1440 ctg ttg aaa aac aag cat acc gca ttg ttc cgc aac cat ttg ggg ccc 1488 acg ccc gaa aaa ctc gcc gcc ttg cgc gag cag ctc ggt ctg ttg ggg 1536 ctt caa ctt ggc ggc ggc gac aac ccg tcg ccg aaa gac tat gcc gcg 1584 ctt gcc gga cag ttc aaa ggc agg ccg gat gcc gaa ttg ctg caa gtc 1632 leu ala gly gln phe lys gly arg pro asp ala glu leu leu gln val atg atg ttg cgc tcc atg caa cag gcg gtt tac gaa ccg cat tgc gac 1680 met met leu arg ser met gln gln ala val tyr glu pro his cys asp gga cac ttt ggt ctt gcc tac gaa gca tac gcc cac ttc acc tcg ccc 1728 atc cgc cgc tat ccc gac ctg acc gta cac cgc gcc atc aaa gcc gtg 1776 ile arg arg tyr pro asp leu thr val his arg ala ile lys ala val ttg aat cag caa acc tac acg cca aaa aaa agc tgg cag gct ttg ggc 1824 leu asn gln gln thr tyr thr pro lys lys ser trp gln ala leu gly gtg cat acc tcg ttc tgt gag cgc cgt gcc gac gac gcc agc cgc gac 1872 gtg gaa aac tgg ctg aaa acc tat tat atg cgc gat aag gtc ggc gaa 1920 val glu asn trp leu lys thr tyr tyr met arg asp lys val gly glu gta ttc gaa ggt aaa atc tcc ggc atg acc agt ttt ggt atc ttt gta 1968 aca ctg gac ggc atc cac att gac ggc ttg gtg cat atc agc gat ttg 2016 ggc gaa gac tat ttc aac ttc cgc ccc gaa atc atg gca atc gaa ggc 2064 gly glu asp tyr phe asn phe arg pro glu ile met ala ile glu gly gaa cgc agc ggc atc cgt ttc aac atg ggg gac agg gtt gcc gtc cgg 2112 glu arg ser gly ile arg phe asn met gly asp arg val ala val arg gtc gcc cgt gcc gat ttg gat gac gga aaa atc gat ttt gtc ctg att 2160 gcc ggg ggg agc ggc agg ggg cgg aaa gtt aaa tca tcc gcg tct gcc 2208 aaa ccg gca ggg acg gcg ggg aaa ggg aag ccg aaa acc gcc gcc gag 2256 aaa aaa aca gcc cga ggc ggc aaa gta agg gga agg ggc gcg tct gcc 2304 gcc gca gaa tcg agg aaa aag gca aag aaa ccg gtt ccg att aag gta 2352 met asn lys asn ile lys ser leu asn leu arg glu lys asp pro phe glu arg arg leu lys ala met ala arg asp gly gln val leu ile asn arg val glu ala his lys asp gly phe gly phe ala val pro leu thr pro ala lys asp gly asp phe val leu tyr glu arg gln met arg gly ser lys val val gly arg phe tyr met asp arg gly val ala ile leu glu pro glu asp lys arg leu asn gln ser ile val leu glu pro asp gly val ala arg phe lys pro glu ser gly gln val ile val gly glu val arg lys his his leu pro his gln phe ser glu ala cys ala lys ala ala lys lys ile pro asp his val arg lys ser asp leu lys gly phe pro arg arg val ile pro met leu pro glu asn leu ser asn gly ile cys ser leu asn pro his val glu arg leu cys val val cys asp met val ile thr tyr ala gly asn ile lys glu tyr arg phe tyr pro ala val met arg ser his ala arg leu thr tyr asn gln val trp lys trp leu ser gly gly ile glu his pro phe lys thr gln ile asp thr ala val glu phe asp ser ile glu thr gln met leu phe asp asp asn gly lys ile glu lys ile val pro val val arg asn asp ala his lys leu ala gly gln phe lys gly arg pro asp ala glu leu leu gln val met met leu arg ser met gln gln ala val tyr glu pro his cys asp ile arg arg tyr pro asp leu thr val his arg ala ile lys ala val leu asn gln gln thr tyr thr pro lys lys ser trp gln ala leu gly val glu asn trp leu lys thr tyr tyr met arg asp lys val gly glu gly glu asp tyr phe asn phe arg pro glu ile met ala ile glu gly glu arg ser gly ile arg phe asn met gly asp arg val ala val arg atg agt atc gta gaa atc aaa gtc ccc gat atc ggc ggt cac gaa aac 48 met ser ile val glu ile lys val pro asp ile gly gly his glu asn gtc gac atc atc gcc gta gaa gtt aaa gcg ggc gac acc atc gcc gtt 96 gac gac acc ctg att aca ctg gaa acc gac aaa gcc acg atg gat gtg 144 cct gcc gat gcg gcc ggt gtc gtg aaa gaa gtg aaa gtc aaa gtc ggc 192 gac aaa atc tcc gaa ggc ggc gta att ctg acc gtt gaa acc ggt gcc 240 gct gcc gca ccc gct gcc gca ggc ggt gca acc gtt caa gta gcc gtt 336 ccc gat atc ggc ggc cat acc gat gtg gat gta atc gcc gtt gaa atc 384 aaa gtg ggc gac acc gtt gcc gaa gac gac acg ctg att act ttg gaa 432 acc gat aaa gcg aca atg gac gta cct tgt acc gct gcc ggt gtc gtt 480 aaa gcc gta ttc tta aaa gtc ggc gac aaa gta tcc gaa ggc tct gcc 528 att atc gaa gta gaa acc gtc ggc tct gcc gca gca gcc cct gct caa 576 atc gac gag gcc gct ttc gcc aaa gca cac gcc ggc cct tcc gca cgc 720 ile asp glu ala ala phe ala lys ala his ala gly pro ser ala arg aaa ctg gcg cgc gaa ttg ggc gtg gat ttg ggc caa gtc aaa ggt acc 768 ggc ttg aaa ggc cgc atc gtg ggc gac gac atc aaa gcc ttt gtg aaa 816 tcc gta atg cag ggc ggc gcg gca aaa cct gcc gca gtc ggc gcg tct 864 tta ggc ggc ggt ctg gac ttg ctg ccc tgg cct aaa gtg gac ttc tcc 912 aaa ttc ggt aat gtc gaa gtt aaa gaa ttg tcc cgc att aag aaa att 960 tcc ggt caa aac ctg tct cgc aac tgg gtg gtg att ccc cac gtt acc 1008 ser gly gln asn leu ser arg asn trp val val ile pro his val thr gta cac gaa gaa gca gat atg acc gag ctg gaa gaa ttc cgc aaa caa 1056 val his glu glu ala asp met thr glu leu glu glu phe arg lys gln ctg aac aaa gaa tgg gaa cgc gaa ggc gtg aaa ctg tca ccg ttg gcg 1104 leu asn lys glu trp glu arg glu gly val lys leu ser pro leu ala ttc atc atc aaa gcc tcc gtt tcc gcg ctg aaa gcc ttc ccc gaa ttc 1152 aac gct tct ctg gac ggc gac aac ttg gtg ctg aaa aac tac ttc aac 1200 atc ggt ttc gca gca gac acg ccg aac ggc ttg gtt gtt cca gta atc 1248 aaa gac gtg gat caa aaa ggc ttg aaa caa atc agc caa gag ctg acc 1296 gaa ttg tct aaa aaa gcc cgc gaa ggc aag ctc aaa cca caa gaa atg 1344 caa ggc gca tgc ttt acc att tcc agc ttg ggc ggc atc ggc ggc aca 1392 ggt ttc acg ccg att gtg aac gct ccc gaa gtc gcc atc ttg ggc gtg 1440 tgc aaa tcc caa atc aaa ccg gtt tgg aac ggc aaa gaa ttc gct cct 1488 cys lys ser gln ile lys pro val trp asn gly lys glu phe ala pro cgc ctg atg tgc cca ttg agc ctg tcc ttt gac cac cgt gtc atc gac 1536 arg leu met cys pro leu ser leu ser phe asp his arg val ile asp ggc gcg gcc ggt atg cgc ttc acc gta ttc ctg gcc aac ctg ttg aaa 1584 met ser ile val glu ile lys val pro asp ile gly gly his glu asn ile asp glu ala ala phe ala lys ala his ala gly pro ser ala arg ser gly gln asn leu ser arg asn trp val val ile pro his val thr val his glu glu ala asp met thr glu leu glu glu phe arg lys gln leu asn lys glu trp glu arg glu gly val lys leu ser pro leu ala cys lys ser gln ile lys pro val trp asn gly lys glu phe ala pro arg leu met cys pro leu ser leu ser phe asp his arg val ile asp atg ttt aag gac gaa cta aat gaa ttt atc cga ttg ata tcc gat ccg 48 met phe lys asp glu leu asn glu phe ile arg leu ile ser asp pro gaa agt gaa ttg gat gaa tgg tat ttg agt gat ttt aaa gat gaa cat 96 ata tgg gaa atg caa agt tac gaa gca ttt tca tgt ttg cgg gaa gca 144 ile trp glu met gln ser tyr glu ala phe ser cys leu arg glu ala gtc ccc tat ttg ttt gct tat ccc cga tac ggg tat gaa ctg ttg gag 192 ata att tcc gcg tta aaa gaa aca tct gat acg aca gaa tta ttt tat 240 gag ccg ggt atc gtg cct ttg ctg att gct tta tat aaa gaa gat agt 288 glu pro gly ile val pro leu leu ile ala leu tyr lys glu asp ser tat ctg gta aat atg gtc aaa cgg ata ttc aaa 321 met phe lys asp glu leu asn glu phe ile arg leu ile ser asp pro ile trp glu met gln ser tyr glu ala phe ser cys leu arg glu ala glu pro gly ile val pro leu leu ile ala leu tyr lys glu asp ser atg gaa aac ggg caa cgg aat aac cgg ttt cct ttg gaa aaa cga att 48 met glu asn gly gln arg asn asn arg phe pro leu glu lys arg ile ttt tat ctg gag cat tcg ggg cgg tat ctg atg att tgc gcc tta tcg 96 phe tyr leu glu his ser gly arg tyr leu met ile cys ala leu ser gat tat tcc caa aac aaa cat act gtc gtt atg gca aat ttc atc tat 144 asp tyr ser gln asn lys his thr val val met ala asn phe ile tyr ccg gat gaa aaa acg gat tgg cgg aat ttg gat gat tta ttc aat gag 192 ttg gtt tta gag gaa ttg cag gct tca ttt atg gat tgg cat ccg act 240 leu val leu glu glu leu gln ala ser phe met asp trp his pro thr gtt gaa gag gca atc agc cgt cat ttg gaa gac ttt tcg 279 met glu asn gly gln arg asn asn arg phe pro leu glu lys arg ile phe tyr leu glu his ser gly arg tyr leu met ile cys ala leu ser asp tyr ser gln asn lys his thr val val met ala asn phe ile tyr leu val leu glu glu leu gln ala ser phe met asp trp his pro thr atg aac ctt gat tta acc gcg caa aaa gtc cgt ctt tct tgg aag gat 48 met asn leu asp leu thr ala gln lys val arg leu ser trp lys asp att ctg tgg ggg tat ggg aat aaa tac ttg ggt tgg gct gat gtg gca 96 gct tat gcc cga aaa atg acg ctt tca gat cat gat gaa cgt gtg ttc 144 ala tyr ala arg lys met thr leu ser asp his asp glu arg val phe aaa cta tct tta atc aac aaa tcc aat att ctt gaa tta aag cct gtt 192 ctg gaa gat ttg gct tcg gaa atg agg gat tat tcc cct aaa aat tgg 240 leu glu asp leu ala ser glu met arg asp tyr ser pro lys asn trp ctg tac gtc ctc tta agc gat gta ttc cat aga aaa gaa gaa ttt gag 288 gat cct ttg ggg gaa gtt gaa aaa att tat gca gat ttt gat tat ccg 336 asp pro leu gly glu val glu lys ile tyr ala asp phe asp tyr pro gaa gaa ata gaa tca ttt gtc agg tat atg ccg ccc aaa gac ggt tat 384 glu glu ile glu ser phe val arg tyr met pro pro lys asp gly tyr att cct tct gcc cac acc tat gaa gaa aat att gcc cgg tta tat tct 432 ile pro ser ala his thr tyr glu glu asn ile ala arg leu tyr ser cac tgg gaa cac tat ttg aac aac ggc gga ggg cag ggt 471 met asn leu asp leu thr ala gln lys val arg leu ser trp lys asp ala tyr ala arg lys met thr leu ser asp his asp glu arg val phe leu glu asp leu ala ser glu met arg asp tyr ser pro lys asn trp asp pro leu gly glu val glu lys ile tyr ala asp phe asp tyr pro glu glu ile glu ser phe val arg tyr met pro pro lys asp gly tyr ile pro ser ala his thr tyr glu glu asn ile ala arg leu tyr ser atg acg gtt gat aag gaa caa gta gaa aag atg att tat tct gaa aat 48 met thr val asp lys glu gln val glu lys met ile tyr ser glu asn aaa cag agt gtt att gac ggt atg ctc ggt atg acc ttc agc tcg gag 96 lys gln ser val ile asp gly met leu gly met thr phe ser ser glu gag gat gaa atc ccc tgg att tcc gag aag ttg acg gag ttg tcg aaa 144 cat aaa gac ttg gat att gcc aga ttg tca tta acc tgt ttc gga cat 192 his lys asp leu asp ile ala arg leu ser leu thr cys phe gly his ctc gcc agg atg cat gaa aat atc ggc gat tgc gat aaa gtg att gct 240 leu ala arg met his glu asn ile gly asp cys asp lys val ile ala tta ttg ctc tca aaa caa ggt gat ccg gat ttt caa ggt ttt gcc gaa 288 gat gcg tta gac gag att tct tta ttt ata ttt aaa aag cgt ccg 333 met thr val asp lys glu gln val glu lys met ile tyr ser glu asn lys gln ser val ile asp gly met leu gly met thr phe ser ser glu his lys asp leu asp ile ala arg leu ser leu thr cys phe gly his leu ala arg met his glu asn ile gly asp cys asp lys val ile ala atg ttg aat cca tcc cga aaa ctg gtt gag ctg gtc cgt att ttg gac 48 met leu asn pro ser arg lys leu val glu leu val arg ile leu asp gaa ggc ggt ttt att ttc agc ggc gat ccc gta cag gcg acg gag gct 96 glu gly gly phe ile phe ser gly asp pro val gln ala thr glu ala ttg cgc cgc gtg gac ggc agt acg gag gaa aaa atc atc cgt cgg gcg 144 leu arg arg val asp gly ser thr glu glu lys ile ile arg arg ala gag atg att gac agg aac cgt atg ctg cgg gag acg ttg gaa cgt gtg 192 cgt gcg ggg tcg ttc tgg ttg tgg gtg gtg gcg gcg acg ttt gca ttt 240 ttt acc ggt ttt tca gtc act tat ctt cta atg gac aat cag ggt ctg 288 phe thr gly phe ser val thr tyr leu leu met asp asn gln gly leu aat ttc ttt ttg gtt ttg gcg ggc gtg ttg ggc atg aat acg ctg atg 336 ctg gca gta tgg ttg gca atg ttg ttc ctg cgt gtg aaa gtg ggg cgt 384 ttt ttc agc agt ccg gcg acg tgg ttt cgg ggc aaa gac cct gta aat 432 phe phe ser ser pro ala thr trp phe arg gly lys asp pro val asn cag gcg gtg ttg cgg ctg tat gcg gac gag tgg cgg caa cct tcg gta 480 gln ala val leu arg leu tyr ala asp glu trp arg gln pro ser val cgt tgg aaa ata ggc gca acg tcg cac agc ctg tgg ctc tgc acg ctg 528 arg trp lys ile gly ala thr ser his ser leu trp leu cys thr leu ctc gga atg ctg gtg tcg gta ttg ttg ctg ctt ttg gtg cgg caa tat 576 acg ttc aac tgg gaa agc acg ctg ttg agc aat gcc gct tcg gta cgc 624 gcg gtg gaa atg ttg gca tgg ctg ccg tcg aaa ctc ggt ttc cct gtc 672 ala val glu met leu ala trp leu pro ser lys leu gly phe pro val ccc gat gcg cgg gcg gtc atc gaa ggc cgt ctg aac ggc aat att gcc 720 gat gcg cgg gct tgg tcg ggg ctg ctg gtc ggc agt atc gcc tgc tac 768 asp ala arg ala trp ser gly leu leu val gly ser ile ala cys tyr ggc atc ctg ccg cgc ctg ctg gct tgg gta gtg tgt aaa atc ctt ttg 816 aaa aca agc gaa aac gga ttg gat ttg gaa aag ccc tat tat cag gcg 864 lys thr ser glu asn gly leu asp leu glu lys pro tyr tyr gln ala gtc atc cgc cgc tgg cag aac aaa atc acc gat gcg gat acg cgt cgg 912 gaa acc gtg tcc gcc gtt tca ccg aaa atc atc ttg aac gat gcg ccg 960 glu thr val ser ala val ser pro lys ile ile leu asn asp ala pro aaa tgg gcg gtc atg ctg gag acc gag tgg cag gac ggc gaa tgg ttc 1008 lys trp ala val met leu glu thr glu trp gln asp gly glu trp phe gag ggc agg ctg gcg cag gaa tgg ctg gat aag ggc gtt gcc acc aat 1056 glu gly arg leu ala gln glu trp leu asp lys gly val ala thr asn cgg gaa cag gtt gcc gcg ctg gag aca gag ctg aag cag aaa ccg gcg 1104 caa ctg ctt atc ggc gtg cgc gcc caa act gtg ccg gac cgc ggc gtg 1152 ttg cgg cag att gtc cga ctc tcg gaa gcg gcg cag ggc ggc gcg gtg 1200 gtg cag ctt ttg gcg gaa cag ggg ctt tca gac gac ctt tcg gaa aag 1248 ctg gaa cat tgg cgt aac gcg ctg gcc gaa tgc ggc gcg gcg tgg ctt 1296 gag cct gac agg gcg gcg cag gaa ggg cgt ttg aaa gac caa 1338 met leu asn pro ser arg lys leu val glu leu val arg ile leu asp glu gly gly phe ile phe ser gly asp pro val gln ala thr glu ala leu arg arg val asp gly ser thr glu glu lys ile ile arg arg ala phe thr gly phe ser val thr tyr leu leu met asp asn gln gly leu phe phe ser ser pro ala thr trp phe arg gly lys asp pro val asn gln ala val leu arg leu tyr ala asp glu trp arg gln pro ser val arg trp lys ile gly ala thr ser his ser leu trp leu cys thr leu ala val glu met leu ala trp leu pro ser lys leu gly phe pro val asp ala arg ala trp ser gly leu leu val gly ser ile ala cys tyr lys thr ser glu asn gly leu asp leu glu lys pro tyr tyr gln ala glu thr val ser ala val ser pro lys ile ile leu asn asp ala pro lys trp ala val met leu glu thr glu trp gln asp gly glu trp phe glu gly arg leu ala gln glu trp leu asp lys gly val ala thr asn atg aac aaa caa ccc ctt tcc ctc gcc gtc gtc ggg cat acc aat acc 48 met asn lys gln pro leu ser leu ala val val gly his thr asn thr ggc aaa acc tcg ctc ctg cgc acc cta ttg cgc gac agc ggc ttc ggc 96 gaa gtc aaa aat gcc ccg tcc act acg cgc cat gtc gaa gaa gcc gcc 144 atc agc gac ggc gca gac acg ctg gtt ttc ctg tat gac acg ccc gga 192 ile ser asp gly ala asp thr leu val phe leu tyr asp thr pro gly ctc gaa gac gcg ggc ggt gtt ttg gaa tgg ctg gaa acc cat acg gat 240 acg cgt tca gac ggc atc gaa cgg ctg caa cag ttt ctc ggc agc cac 288 thr arg ser asp gly ile glu arg leu gln gln phe leu gly ser his ggc gcg cac cat gat ttc aat cag gaa gcc aaa gtc tta cgg caa gtc 336 gly ala his his asp phe asn gln glu ala lys val leu arg gln val ttg caa agc gat atg gca atg tac gtc atc gac gcg cgc gaa ccc gtc 384 leu gln ser asp met ala met tyr val ile asp ala arg glu pro val ctc gac aaa tac agg gac gag ttg acc atc ctt tca tgg tgt gcc aaa 432 leu asp lys tyr arg asp glu leu thr ile leu ser trp cys ala lys ccg gtt atg ccc gtg ttc aac ttt acc ggc gga cag cct ccc gaa tcg 480 tgg aca acc atg ctg gcg agg aga aac ctg cac gtt ttc gca ggg ttc 528 trp thr thr met leu ala arg arg asn leu his val phe ala gly phe gac acc gtc gcc ttt gat ttt gaa ggc gaa cta cgc ctg tgg gaa aac 576 asp thr val ala phe asp phe glu gly glu leu arg leu trp glu asn ctc gcc acc atg ttg ccc gaa cgc agc aca ctt gac cgc ctg aca gcc 624 atg cgc cgg cgc gaa tgg cag cgg ctg gac ggc gaa gcg cgc cgc gaa 672 atc gcc gac ttt tta att gat gcc gcc gcc ttc agg cag gaa gtg gac 720 gaa aac gag gat acc gcc acc gtg ccg caa acc atg cag gcg gaa ata 768 cgc caa ctc gaa cgg cag atg cag cag cgg ctg ttt gcc ctt tac cgt 816 ttc tac cac agc gaa atc gac ggc ggc gac tgg atg ccg caa gcc ttc 864 phe tyr his ser glu ile asp gly gly asp trp met pro gln ala phe cgc caa gac ccg ttc gac agc gaa ttg ctc aaa caa tac ggc atc cgc 912 arg gln asp pro phe asp ser glu leu leu lys gln tyr gly ile arg acc ggc acg ggc gcg gca acc ggc gcg ctc atc ggc ttg ggg ctg gac 960 atc gcc aca ctc ggc ggc tcg ctc gga ttg ggt acg gca atc ggc ggc 1008 ttt ttg ggc ggc atc ctg ccc aat acc cgc acc att tct gac aaa ctc 1056 phe leu gly gly ile leu pro asn thr arg thr ile ser asp lys leu gcc ggc cgt caa acc ctg cac acc gac ccc gaa acc ctg acc ctg ctc 1104 gcc gcc cgc gcc ctc gat ctg ctc cac gtc ctg caa acg cgc gga cac 1152 gcg gca cag tcg gat atc gag ctg cac agc cgc aaa gtc ccg tgg gat 1200 ala ala gln ser asp ile glu leu his ser arg lys val pro trp asp gcc gcc aga ctc ccg ccc gaa ctc aac aaa gcc cgc agt cat tgg aaa 1248 tgg tcg tcg ctc aat acg cac cgc ccg gaa acc agc cgc gcc gaa cgc 1296 gcc gga tat gtg gag aaa ctt caa atc cgc ctg tcg gga aaa tat agt 1344 ala gly tyr val glu lys leu gln ile arg leu ser gly lys tyr ser gaa tta aat tta aat cag gac aag gcg gcg agc cgc aga cag tac aaa 1392 met asn lys gln pro leu ser leu ala val val gly his thr asn thr ile ser asp gly ala asp thr leu val phe leu tyr asp thr pro gly thr arg ser asp gly ile glu arg leu gln gln phe leu gly ser his gly ala his his asp phe asn gln glu ala lys val leu arg gln val leu gln ser asp met ala met tyr val ile asp ala arg glu pro val leu asp lys tyr arg asp glu leu thr ile leu ser trp cys ala lys trp thr thr met leu ala arg arg asn leu his val phe ala gly phe asp thr val ala phe asp phe glu gly glu leu arg leu trp glu asn phe tyr his ser glu ile asp gly gly asp trp met pro gln ala phe arg gln asp pro phe asp ser glu leu leu lys gln tyr gly ile arg phe leu gly gly ile leu pro asn thr arg thr ile ser asp lys leu ala ala gln ser asp ile glu leu his ser arg lys val pro trp asp ala gly tyr val glu lys leu gln ile arg leu ser gly lys tyr ser atg aaa acc tcc gaa ctg cgc caa aaa ttc cta aaa ttt ttt gaa acc 48 aaa ggc cac acc gtc gtc cgc tct tcc agc ctc gtg ccg cac gac gac 96 ccg acc ctg ctg ttt acc aac gcg ggc atg aac cag ttt aaa gac gta 144 pro thr leu leu phe thr asn ala gly met asn gln phe lys asp val ttc tta ggt ttc gac aaa cgc ccg tac agc cgc gcc acc acc gcg caa 192 phe leu gly phe asp lys arg pro tyr ser arg ala thr thr ala gln aaa tgc gta cgc gca ggc ggc aaa cac aac gac ttg gaa aac gtc ggc 240 lys cys val arg ala gly gly lys his asn asp leu glu asn val gly tac acc gcc cgc cac cac acc ttc ttt gaa atg atg ggc aac ttc tcc 288 tyr thr ala arg his his thr phe phe glu met met gly asn phe ser ttc ggc gac tac ttc aaa cgc gac gcc atc cac ttc gct tgg gaa ttt 336 phe gly asp tyr phe lys arg asp ala ile his phe ala trp glu phe ctg act tcc ccc gaa tgg ctc aac atc cct aaa gac aaa ctg ttg gcg 384 leu thr ser pro glu trp leu asn ile pro lys asp lys leu leu ala acc gtt tac gcg gaa gac gac gaa gcc tac aac atc tgg ttg aac gaa 432 atc ggt atg ccg tcc gag cgc atc gtc cgc atc ggc gac aac aaa ggc 480 ile gly met pro ser glu arg ile val arg ile gly asp asn lys gly gcg aaa tac gca tcc gac aac ttc tgg caa atg ggc gac acc ggc cct 528 ala lys tyr ala ser asp asn phe trp gln met gly asp thr gly pro tgc ggc ccc tgc tcc gaa att ttc tac gac cac ggc gaa gaa atc tgg 576 cys gly pro cys ser glu ile phe tyr asp his gly glu glu ile trp ggc ggc att ccc ggc agt ccc gaa gaa gac ggc gac cgc tgg atc gaa 624 att tgg aac tgc gta ttt atg cag ttc aac cgc gac gaa caa ggc aat 672 ile trp asn cys val phe met gln phe asn arg asp glu gln gly asn atg aac ccg ctt ccc aaa cct tcc gtc gat acc ggt atg ggc ttg gaa 720 met asn pro leu pro lys pro ser val asp thr gly met gly leu glu cgc ata gcc gcc gtc atg cag cat gtt cac agc aac tac gaa atc gac 768 arg ile ala ala val met gln his val his ser asn tyr glu ile asp ttg ttc caa gac ctg ctc aaa gcc gtt gcc cgc gaa acc ggc gcg ccg 816 leu phe gln asp leu leu lys ala val ala arg glu thr gly ala pro ttc aga atg gaa gaa ccc agc ctg aaa gtc atc gcc gac cac atc cgc 864 phe arg met glu glu pro ser leu lys val ile ala asp his ile arg tcc tgc tcg ttc ctg att gca gac ggc gtc ttg cct tcc aac gaa ggc 912 ser cys ser phe leu ile ala asp gly val leu pro ser asn glu gly cgc ggc tac gta ttg cgc cgc att atc cgc cgc gcc gtg cgc cac ggt 960 tac aaa ctg ggt caa agc aaa ccg ttc ttc cac aaa ctc gtt gcc gat 1008 tyr lys leu gly gln ser lys pro phe phe his lys leu val ala asp ttg gtc aaa gag atg ggc ggt gcc tac cct gaa ttg aaa gaa aaa caa 1056 gcc caa atc gaa gaa gca ttg aaa aac gaa gaa agc cgt ttt gcc caa 1104 acg ctg gaa acc ggt atg gct ttg ttg gaa aac gcg ctg gtc aaa ggc 1152 ggc aaa aca ctc ggc ggc gaa atc atc ttc aaa ctc tac gat acc tac 1200 ggt ttc cca tac gac ttg act gcc gac atc tgc cgc gaa cgc aat atc 1248 gly phe pro tyr asp leu thr ala asp ile cys arg glu arg asn ile gaa ccg gac gaa gca ggc ttc gag cgc gaa atg gaa gcc caa cgc gca 1296 cgc gca cgc gcc gcc caa agc ttc aaa gcc aac gcc caa ctg cct tat 1344 gac ggt caa gac acc gag ttt aaa ggt tat agc gaa cgc caa acc gaa 1392 tcc aaa gtc ctc gcc ctc tac aaa gac ggc gag caa gtc aac gaa ttg 1440 ser lys val leu ala leu tyr lys asp gly glu gln val asn glu leu aac gaa ggc gac agc ggc gca gtc gtc atc gac ttt acc ccg ttc tat 1488 asn glu gly asp ser gly ala val val ile asp phe thr pro phe tyr gca gaa tcc ggc ggc caa gtc ggc gat gtc ggc tat atc ttc tca ggc 1536 gaa aac cgc ttt gaa gta cgc gat acc caa aaa atc aaa gcg gcc gta 1584 glu asn arg phe glu val arg asp thr gln lys ile lys ala ala val ttc ggt caa ttc ggc gta caa act tca ggc cgt ctg aaa gtc ggc gac 1632 agc gtt acc gcc aaa gtg gac gac gaa atc cgc aat gcc aat atg cgc 1680 ser val thr ala lys val asp asp glu ile arg asn ala asn met arg aac cac agc gca acc cac ttg atg cac aaa gcc ctg cgc gat gta ttg 1728 asn his ser ala thr his leu met his lys ala leu arg asp val leu ggc aga cac gtc gaa caa aaa ggc tct ttg gtt acc gcc gaa tcc acc 1776 gly arg his val glu gln lys gly ser leu val thr ala glu ser thr cgt ttc gac att tcc cat ccc caa gcg gta act gcc gaa gaa att gcc 1824 arg phe asp ile ser his pro gln ala val thr ala glu glu ile ala gaa gta gaa cgc cgc gtc aac gaa gcc att ttg gcg aac gtt gcc gtc 1872 aat gca gcc att atg agc atg gaa gac gcg caa aaa acc ggc gcg atg 1920 asn ala ala ile met ser met glu asp ala gln lys thr gly ala met atg ctc ttc ggc gaa aaa tac ggc gaa gaa gtg cgc gta ctg caa atg 1968 ggc ggt ttc tct acc gaa ttg tgc ggc ggc aca cac gtt tca cgc acc 2016 ggc gac atc ggc ctc ttc aaa atc atc agc gaa ggc ggt att gcc gca 2064 ggc gtg cgc cgt atc gaa gcc atc acc ggc ctg aac gca ctc aaa tgg 2112 gly val arg arg ile glu ala ile thr gly leu asn ala leu lys trp gcg caa gag caa gag cgt ttg gtg aaa gac att att gcc gaa acc aaa 2160 gcc caa acc gaa aaa gac gta ctg gca aaa atc caa gca ggc gcg gca 2208 gcc gtc cac gca ggc gcc aaa ctc ttg gac gat gca aaa gac ttg ggc 2304 gca gcc aaa ctc gtt gcc gcc caa atc gaa gcc gac gca gcc gcc ctg 2352 cgc gaa atc gtt acc gat tta acc ggt aaa tcc gac aac gcc gtg att 2400 arg glu ile val thr asp leu thr gly lys ser asp asn ala val ile ctt tta gcg gca gta aac gac ggc aaa gtc tcc ctg tgc gcc ggc gta 2448 tcc aaa ccg ttg acc ggc aaa gtg aaa gca ggc gat ctg gtt aaa ttt 2496 gca gcc gaa caa gtc ggc ggc aaa ggc ggc ggc aga cca gat ttg gcg 2544 caa gcc ggc ggc acg gat gcc gac aaa ttg ccc gcc gtg ttg gat agc 2592 gtg aaa gac tgg gtc ggc gcg aag ctg gtt 2622 pro thr leu leu phe thr asn ala gly met asn gln phe lys asp val phe leu gly phe asp lys arg pro tyr ser arg ala thr thr ala gln lys cys val arg ala gly gly lys his asn asp leu glu asn val gly tyr thr ala arg his his thr phe phe glu met met gly asn phe ser phe gly asp tyr phe lys arg asp ala ile his phe ala trp glu phe leu thr ser pro glu trp leu 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lys asp ala pro lys asp phe ser ala arg ile gca ggc aaa gac ccc gcg caa agc atc cgc atc aaa ccc gaa gac gat 336 ttg gca ggc atc aaa agc cgt gcc aaa tac acc gag gtt tac ttg gta 384 leu ala gly ile lys ser arg ala lys tyr thr glu val tyr leu val aaa ggt gaa gac ggc aaa atc ggc caa atc atc ctg cct atg cac ggt 432 aac ggt ttg tgg tcg gtc atg tac ggc ttt gtc gcc atc caa ccc gac 480 asn gly leu trp ser val met tyr gly phe val ala ile gln pro asp ggc aac acc atc aac ggc att acc tac tac gag caa ggc gaa acc ccg 528 ggc tta ggc ggc gaa atc ggc aat cct ttg tgg cag caa aaa ttc gtc 576 gly leu gly gly glu ile gly asn pro leu trp gln gln lys phe val ggc aaa aaa ctg ttt gac gga caa ggc aaa ctc gcc ctg cac gtc ggc 624 aaa ggc gcg ggt tcg gac aaa gaa cac ggc gta gat gcc ctc tcc ggc 672 gcg tcg ctg aca tcc aaa ggc gta caa ggt tcg ttc gcc tac tgg ttc 720 ala ser leu thr ser lys gly val gln gly ser phe ala tyr trp phe ggc gaa aac ggc tat atc ccc tac ctg aac aaa ttg aaa tca gca gga 768 met ala lys lys phe 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cat gcc agc atc gat acc gcc gtg gaa gcc acc aaa 288 met met ser gly his ala ser ile asp thr ala val glu ala thr lys atc ggc gcg atc gat ttt ttg gaa aaa ccg att tcc ctg caa aag ctg 336 ile gly ala ile asp phe leu glu lys pro ile ser leu gln lys leu ctg tct gcc gtc gaa aac gcg ttg aag tac ggt gcg gcg caa acc gaa 384 leu ser ala val glu asn ala leu lys tyr gly ala ala gln thr glu acg ggg cct gta ttc gac aag ctg ggc aac agt gcg gcg att cag gaa 432 thr gly pro val phe asp lys leu gly asn ser ala ala ile gln glu atg aac cgt gag gta ggg gct gcg gtg aaa tgt gcc tct ccc gta ctt 480 met asn arg glu val gly ala ala val lys cys ala ser pro val leu ttg acg ggc gag gcg ggt tcg ccg ttt gaa acg gtg gca cgc tat ttc 528 leu thr gly glu ala gly ser pro phe glu thr val ala arg tyr phe cat aaa aac ggt acg ccg tgg gtc agc ccg gca agg gtc gaa tat ctg 576 his lys asn gly thr pro trp val ser pro ala arg val glu tyr leu atc gat atg ccg atg gaa ctg ttg cag aag gcg gag ggc ggc gtt ttg 624 ile asp met pro met glu leu leu gln lys ala glu gly gly val leu tat gtc ggc gac atc gcc cag tac agc cgc aac atc caa gcc ggt att 672 gcc ttt att gtc gga aag gcg gaa cac cgc cgc gtc agg gtg gtc gca 720 tcg ggc agc agg gcg gca ggt tca gac ggc att gcc tgc gag gaa aag 768 atg cag cat gaa gac att ccc ttc ctg ata cag ggg att gcc tgc aat 864 met gln his glu asp ile pro phe leu ile gln gly ile ala cys asn gtg gcg gaa agc caa aag att gcg cct gcc tca ttc agt gaa gag gca 912 ctt gcc gca ttg acc cgt tac gac tgg ccg gga aat ttc gac caa ctg 960 leu ala ala leu thr arg tyr asp trp pro gly asn phe asp gln leu caa agc gtc gtt gca acg ctg ttg ttg gag gcg gac gga cag gaa atc 1008 ggc gca ggg gcg gtt tct tcc ctt ttg ggg cag aat gtg cct gcc gag 1056 ggg gcg gaa gat atg gtg ggc ggg ttt aat ttc aac ctg ccc ctg cgc 1104 gly ala glu asp met val gly gly phe asn phe asn leu pro leu arg gaa ttg agg gag gag gtg gag cgg cgt tat ttc gag tac cac atc gcc 1152 caa gaa ggt cag aat atg agc caa gtg gcg cag aaa gtt ggt ttg gaa 1200 cgc acg cac ctt tac cgc aaa ctc aaa cag ctc ggc atc ggc gtt tcg 1248 arg thr his leu tyr arg lys leu lys gln leu gly ile gly val ser ala met val leu leu asp ile trp met pro asp cys asp gly ile thr leu leu lys glu trp ala lys asn gly gln leu asn met pro val val met met ser gly his ala ser ile asp thr ala val glu ala thr lys ile gly ala ile asp phe leu glu lys pro ile ser leu gln lys leu leu ser ala val glu asn ala leu lys tyr gly ala ala gln thr glu thr gly pro val phe asp lys leu gly asn ser ala ala ile gln glu met asn arg glu val gly ala ala val lys cys ala ser pro val leu leu thr gly glu ala gly ser pro phe glu thr val ala arg tyr phe his lys asn gly thr pro trp val ser pro ala arg val glu tyr leu ile asp met pro met glu leu leu gln lys ala glu gly gly val leu met gln his glu asp ile pro phe leu ile gln gly ile ala cys asn leu ala ala leu thr arg tyr asp trp pro gly asn phe asp gln leu gly ala glu asp met val gly gly phe asn phe asn leu pro leu arg arg thr his leu tyr arg lys leu lys gln leu gly ile gly val ser atg aca gag gac gaa cgt ttc gcg tgg ctg caa ttg gcg ttt acg ccc 48 met thr glu asp glu arg phe ala trp leu gln leu ala phe thr pro tat atc ggc gcg gaa agt ttc ctg ctg ctg atg cgc cgt ttc ggc agc 96 gcg caa aat gcc ctg tcc gca ccg gcg gaa cag gtg gcg gca ctg ata 144 cgg cac aaa cag gcg ctt gag gct tgg cgc aat gcg gaa aaa cgc gct 192 ctg gcg cgg cag gcg gca gaa gcg gca ttg gaa tgg gaa atg cgg gac 240 gga tgc cgc ctg atg ctg ctt cag gat gaa gat ttt ccc gaa atg ctg 288 acg cag ggg ctg acc gcg cca ccg gtt ttg ttt ttg cgc ggc aac gtg 336 caa ctg ctg cac aaa cct tcc gcc gcc atc gtc ggc agc cgt cat gcc 384 gln leu leu his lys pro ser ala ala ile val gly ser arg his ala acg ccg cag gcg atg cgg att gcc aaa gat ttc ggc aag tcg ttg ggt 432 thr pro gln ala met arg ile ala lys asp phe gly lys ser leu gly ggg aaa ggc att ccc gtt gtg tcg ggt atg gct tcg ggc atc gat acc 480 gcc gcc cat cag ggt gcg ttg cag gca gaa ggc ggc acc atc gcc gtg 528 tgg ggg acg ggc ata gac cgc att tat ccg ccg gtc aac aaa aac ctt 576 trp gly thr gly ile asp arg ile tyr pro pro val asn lys asn leu gcc tat gaa atc gcc gaa aaa gga ttg att gtc agc gag ttc ccc atc 624 ala tyr glu ile ala glu lys gly leu ile val ser glu phe pro ile ggc acg cgg ccg tat gcc ggc aat ttt ccg cgc cgc aac cgc ctg att 672 gcc gcc ctg tcg caa gta acg ctg gtg gtt gaa gcc gcg ttg gaa tcc 720 ggt tcg ctg att act gcc aga ttg gcg gcg gag atg ggg cgc gaa gtg 768 atg gcg gta ccc ggc tcg ata gac aat cca cac agt aaa ggc tgc cac 816 met ala val pro gly ser ile asp asn pro his ser lys gly cys his aaa ctg att aaa gac ggc gca aaa ttg gtg gaa tgc ctg gac gac atc 864 ctg aac gaa tgc ccg ggg cta ttg caa aat acg ggt gct tca tca tat 912 leu asn glu cys pro gly leu leu gln asn thr gly ala ser ser tyr tct ata aat aag gga ata cct gaa aag cgc atc act gcc gtt cag acg 960 ser ile asn lys gly ile pro glu lys arg ile thr ala val gln thr gca tcc gac cag ctg tct ctg cct gaa ggc aaa atg ccg tct gaa aag 1008 acg gag aac cga ccc gtc ggc ggc agt atc ttg gac agg atg ggt ttc 1056 thr glu asn arg pro val gly gly ser ile leu asp arg met gly phe gac cca gtt cat ccc gac gtg ctt gcc gga cag ttg gct atg cct gcc 1104 gca gat ttg tat gcc gca ctg ttg gaa ttg gaa ttg gac ggc agc gtt 1152 gcc gca atg ccc ggc ggc aga tac cag cgt atc cga act 1191 met thr glu asp glu arg phe ala trp leu gln leu ala phe thr pro gln leu leu his lys pro ser ala ala ile val gly ser arg his ala thr pro gln ala met arg ile ala lys asp phe gly lys ser leu gly trp gly thr gly ile asp arg ile tyr pro pro val asn lys asn leu ala tyr glu ile ala glu lys gly leu ile val ser glu phe pro ile met ala val pro gly ser ile asp asn pro his ser lys gly cys his leu asn glu cys pro gly leu leu gln asn thr gly ala ser ser tyr ser ile asn lys gly ile pro glu lys arg ile thr ala val gln thr thr glu asn arg pro val gly gly ser ile leu asp arg met gly phe atg acc gaa gtc atc gcc tac ctc atc gaa cat ttc caa gat ttc gat 48 met thr glu val ile ala tyr leu ile glu his phe gln asp phe asp acc tgc ccg ccg ccc gaa gac ttg ggt atg ctg ctt gaa gaa gcg ggt 96 ttc gat acg atg gaa atc ggc aac acc ctg atg atg atg gaa gta ttg 144 ctc aac agc tcc gaa ttt tcc gcc gaa ccc gcc gac agc ggc gca ttg 192 cgc gtg tac agc aaa gaa gaa acc gac aac ctg ccg cag gaa gtg atg 240 arg val tyr ser lys glu glu thr asp asn leu pro gln glu val met ggg ctg atg cag tat ctg att gaa gaa aaa gcc gtc agc tgc gaa cag 288 gly leu met gln tyr leu ile glu glu lys ala val ser cys glu gln cgg gaa atc atc atc cac gcg ctc atg cac att ccg ggc gac gaa att 336 acc gta gat acc gcc aaa gtg ctg acc ctg ctg ctt tta tgg gca aac 384 aag agc gag ctg ccc gtg ttg gtc ggc gac gag ctg atg agc gcg ctt 432 met thr glu val ile ala tyr leu ile glu his phe gln asp phe asp arg val tyr ser lys glu glu thr asp asn leu pro gln glu val met gly leu met gln tyr leu ile glu glu lys ala val ser cys glu gln atg acg gtt ttg aag ctt tcg cac tgg cgg gtg ttg gcg gag ctt gcc 48 met thr val leu lys leu ser his trp arg val leu ala glu leu ala gac ggt ttg ccg caa cac gtc tcg caa ctg gcg cgt atg gcg gat atg 96 asp gly leu pro gln his val ser gln leu ala arg met ala asp met aag ccg cag cag ctc aac ggt ttt tgg cag cag atg ccg gcg cac ata 144 lys pro gln gln leu asn gly phe trp gln gln met pro ala his ile cgc ggg ctg ttg cgc caa cac gac ggc tat tgg cgg ctg gtg cgc cca 192 ttg gcg gtt ttc gat gcc gaa ggt ttg cgc gag ctg ggg gaa agg tcg 240 ggt ttt cag acg gca ttg aag cac gag tgc gcg tcc agc aac gac gag 288 gly phe gln thr ala leu lys his glu cys ala ser ser asn asp glu ata ctg gaa ttg gcg cgg att gcg ccg gac aag gcg cac aaa acc ata 336 tgc gtg acc cac ctg caa agt aag ggc agg ggg cgg cag ggg cgg aag 384 tgg tcg cac cgt ttg ggc gag tgt ctg atg ttc agt ttt ggc tgg gtg 432 trp ser his arg leu gly glu cys leu met phe ser phe gly trp val ttt gac cgg ccg cag tat gag ttg ggt tcg ctg tcg cct gtt gcg gca 480 phe asp arg pro gln tyr glu leu gly ser leu ser pro val ala ala gtg gcg tgt cgg cgc gcc ttg tcg cgt tta ggt ttg gat gtg cag att 528 aag tgg ccc aat gat ttg gtt gtc gga cgc gac aaa ttg ggc ggc att 576 ctg att gaa acg gtc agg acg ggc ggc aaa acg gtt gcc gtg gtc ggt 624 atc ggc atc aat ttt gtc ctg ccc aag gaa gta gaa aat gcc gct tcc 672 ile gly ile asn phe val leu pro lys glu val glu asn ala ala ser gtg caa tcg ctg ttt cag acg gca tcg cgg cgg ggc aat gcc gat gcc 720 val gln ser leu phe gln thr ala ser arg arg gly asn ala asp ala caa tat gcg cgg gac gga ttt gcg cct ttt gtg gcg gaa tat cag gct 816 gcc aac cgc gac cac ggc aag gcg gta ttg ctg ttg cgc gac ggc gaa 864 acc gtg ttc gaa ggc acg gtt aaa ggc gtg gac gga caa ggc gtt ttg 912 cac ttg gaa acg gca gag ggc aaa cag acg gtc gtc agc ggc gaa atc 960 his leu glu thr ala glu gly lys gln thr val val ser gly glu ile agc ctg cgg tcc gac gac agg ccg gtt tcc gtg ccg aag cgg cgg gat 1008 tcg gaa cgt ttt ctg ctg ttg gac ggc ggc aac agc cgg ctc aag tgg 1056 gcg tgg gtg gaa aac ggc acg ttc gca acc gtc ggt agc gcg ccg tac 1104 ala trp val glu asn gly thr phe ala thr val gly ser ala pro tyr cgc gat ttg tcg cct ttg ggc gcg gag tgg gcg gaa aag gcg gat gga 1152 aat gtc cgc atc gtc ggt tgc gct gtg tgc gga gaa ttc aaa aag gca 1200 caa gtg cag gaa cag ctc gcc cga aaa atc gag tgg ctg ccg tct tcc 1248 gln val gln glu gln leu ala arg lys ile glu trp leu pro ser ser gca cag gct ttg ggc ata cgc aac cac tac cgc cac ccc gaa gaa cac 1296 ala gln ala leu gly ile arg asn his tyr arg his pro glu glu his ggt tcc gac cgc tgg ttc aac gcc ttg ggc agc cgc cgc ttc agc cgc 1344 aac gcc tgc gtc gtc gtc agt tgc ggc acg gcg gta acg gtt gac gcg 1392 ctc acc gat gac gga cat tat ctc ggg gga acc atc atg ccc ggt ttc 1440 cac ctg atg aaa gaa tcg ctc gcc gtc cga acc gcc aac ctc aac cgg 1488 his leu met lys glu ser leu ala val arg thr ala asn leu asn arg cac gcc ggt aag cgt tat cct ttc ccg acc aca acg ggc aat gcc gtc 1536 his ala gly lys arg tyr pro phe pro thr thr thr gly asn ala val gcc agc ggc atg atg gat gcg gtt tgc ggc tcg gtt atg atg atg cac 1584 ggg cgt ttg aaa gaa aaa acc ggg gcg ggc aag cct gtc gat gtc 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ile lys gly leu leu gly lys trp ser his val gcc agc agg agc gtc gaa aaa cgc acc gcc caa gcc aaa cct gcc gac 528 aaa acc tac cgc gtc gtc ctg ccc gtt tcc gcc gat gcc gaa aat cag 576 lys thr tyr arg val val leu pro val ser ala asp ala glu asn gln gcg gcg gag ctg tct gcc aaa ggt ttc aac ccc ata ccg ttt gac ggc 624 ala ala glu leu ser ala lys gly phe asn pro ile pro phe asp gly gca ttg agt ttg ggt gtc ggc aac agc cgg gaa aac gcc caa gcc ctg 672 caa aac cgg ctt gcc ggc gcc gga ttc ggc ggg gcg cat att gtc gaa 720 gln asn arg leu ala gly ala gly phe gly gly ala his ile val glu cac ttt gcc gaa gcc gac agg cag gac gat tct ttg agc gtg tcg cgt 768 atg acg gtt ttg ttt acc ggc gtg aat gcc gcc gat gcg gac gaa att 816 met thr val leu phe thr gly val asn ala ala asp ala asp glu ile cgt aaa atc acg tcc cta tac ggc aaa ctg aac ctc aag tct tgc aaa 864 asp asp tyr his arg ile lys gly leu leu gly lys trp ser his val lys thr tyr arg val val leu pro val ser ala asp ala glu asn gln ala ala glu leu ser ala lys gly phe asn pro ile pro phe asp gly gln asn arg leu ala gly ala gly phe gly gly ala his ile val glu met thr val leu phe thr gly val asn ala ala asp ala asp glu ile atg aaa caa gct atg aaa aat tgg ttt gct gcc ttg ctg ttg gca gta 48 ccc atg ggt gcg gca ttt gct tcg ggc ggt cat gca cac tat gag aaa 96 gtc gat atc gat ttg cgc gac caa gtc agc ctg cag cgc ggc gca caa 144 atc ttt acc aac tat tgc ctg tcc tgc cac tcg gca agc ggt atg cgt 192 ile phe thr asn tyr cys leu ser cys his ser ala ser gly met arg ttc aac cgt ttg aaa gac atc ggt ttg act gac gaa gaa atc aag aaa 240 aac ctg atg ttt acc acc gat aat gtc ggc gat gtc atg cat tcg gcg 288 asn leu met phe thr thr asp asn val gly asp val met his ser ala atg aac ccg aaa gat gcg gca aaa tgg ttt ggt gct gct ccg ccc gat 336 ttg aca ttg att gcg cgt tcc aaa ggt gca gac tac ctt tac gct tat 384 atg cgc ggc ttc tat aaa gat ccg acc cgt ccg agc ggc tgg aac aat 432 met arg gly phe tyr lys asp pro thr arg pro ser gly trp asn asn act gta ttc gat aaa gtc ggt atg ccc cac ccg ttg tgg gaa cag caa 480 thr val phe asp lys val gly met pro his pro leu trp glu gln gln ggc gtt caa gcc gtt gag ttg gat gcc aaa ggt cag ccg gtt atg gta 528 aaa gac gaa cac ggc gag atg aag cct aag ctg tat tgg gaa tct acc 576 lys asp glu his gly glu met lys pro lys leu tyr trp glu ser thr ggt ttg cac agc cgc cgt ctg cct aac ggc aaa gtg atc caa aaa gag 624 gly leu his ser arg arg leu pro asn gly lys val ile gln lys glu tac gac gca tat gta cgc gat ttg gtc aat tac ctt gtg tac atg ggc 672 gaa cct gca caa ctg caa cgc aaa cgt ata ggc tat gtc gtg atg att 720 glu pro ala gln leu gln arg lys arg ile gly tyr val val met ile ttc cta ttt gcg gtt atg ctg cct ttg gcg tat ttc ctg aaa aaa gaa 768 ile phe thr asn tyr cys leu ser cys his ser ala ser gly met arg asn leu met phe thr thr asp asn val gly asp val met his ser ala met arg gly phe tyr lys asp pro thr arg pro ser gly trp asn asn thr val phe asp lys val gly met pro his pro leu trp glu gln gln lys asp glu his gly glu met lys pro lys leu 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caa atc cgc 432 caa aga atc gaa acc gat ttg gaa gaa agc cgc caa act gtc cgc gac 480 gtg caa aac gac ctt tcc gat gtc ggc aac cgt ttt gcc gca gcc gaa 528 val gln asn asp leu ser asp val gly asn arg phe ala ala ala glu aaa cag att gcc cat ttg cag gaa aaa gag gcg gaa gcg gag cgg ttg 576 agg cag tcg cat acc gag ttg cag gaa aag gca cag ggt ttg gcg gtt 624 arg gln ser his thr glu leu gln glu lys ala gln gly leu ala val gaa aac gaa cgt ttg gca acg caa atc gaa cag gaa cgc ctt gct tct 672 gaa gag aag ctg tcc ttg ctg ggc gag gcg cgc aaa agt ttg agc gat 720 cag ttt caa aat ctt gcc aac acg att ttg gaa gaa aaa agc cgc cgt 768 gln phe gln asn leu ala asn thr ile leu glu glu lys ser arg arg ttt acc gag cag aac cgc gag cag ctc cat cag gtt ttg aac ccg cta 816 aac gaa cgc atc cac ggt ttc ggc gag ttg gtc aag caa acc tat gat 864 asn glu arg ile his gly phe gly glu leu val lys gln thr tyr asp aaa gaa tcg cgc gag cgg ctg acg ttg gaa aac gaa ttg aaa cgg ctt 912 cag ggg ttg aac gcg cag ctg cac agc gag gca aag 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gtg atc 192 gaa ggg ccg acc ggc gtg ggc aaa tcg ttg gcc tac ctt ttg gcc ggc 240 ggc atc atg gcg caa aca cgc ggc aag cgg ctg att gtg agc agc gcg 288 gly ile met ala gln thr arg gly lys arg leu ile val ser ser ala acg gtt gcc ttg cag gag cag ttg gta gac cgc gac ctg ccg ttt ctg 336 gtc gaa aaa agc ggt ttg gaa ctg acc ttc gca ctt gcc aaa ggg cgc 384 ggc cgc tat ctc tgc ccc tac aaa ctc tat cga ctg acg caa agc aat 432 gly arg tyr leu cys pro tyr lys leu tyr arg leu thr gln ser asn gcc cag caa aac ctg ctc ggc ttt gaa gcc ccc gcc gtc ttg tgg gac 480 ala gln gln asn leu leu gly phe glu ala pro ala val leu trp asp agc aaa ccc aag ccc gaa gaa ttg aag ctg ctg cgc gac atc gcc gac 528 gaa ttt tcc gcc cga cgg ttc aac ggc gac cgc gac act tgg ccg gaa 576 glu phe ser ala arg arg phe asn gly asp arg asp thr trp pro glu aaa atc gat gac gcg att tgg ctc aaa gtg acc aac gac cgc cac ggc 624 lys ile asp asp ala ile trp leu lys val thr asn asp arg his gly tgc ctg aaa acc gcc tgt ccc aac cgt ccg gaa tgt ccg ttt tac cta 672 cys leu lys thr ala cys pro asn arg pro glu cys pro phe tyr leu gca cgc gat gtc ttg gaa acc gtc gat gtc gtc gtt gcc aac cac gat 720 ctt ctg ctt gcc gac atc agt atg ggc ggc ggc gtg att ctg cct gcg 768 ccc gaa aac agt ttc tat tgc atc gac gaa gcg cac cac ctg ccc aaa 816 pro glu asn ser phe tyr cys ile asp glu ala his his leu pro lys aaa gcc ctc agc cgt ttt gcc gcc gaa cat tca tgg aat att gcc gtt 864 lys ala leu ser arg phe ala ala glu his ser trp asn ile ala val tgg acg ctg gaa aaa ctg ccg cag ctg acc ggc aaa att gcc gcg ctg 912 acc gat aaa gcc gaa ctt gcc aac cta gcc gac gaa gcc gcc gca tcc 960 ttg ctc gac agc ctg cat gaa tgg caa ttc cat ttg gcg gaa gag ccg 1008 tct tta agt ctg ggg gtg tct gaa aac gac aga cga acc aac agc gaa 1056 ccg act tgg ctg tgg gaa gac ggc aaa atc ccc gaa ggc ctc gaa acc 1104 acc gtt tcc aat acg gcc att gct gcg cgc agc ctg ctc aaa cac gtt 1152 atc ggg ctg aac gat gcg ctt tct gcc gca cgc cgc gaa aaa gaa cag 1200 ile gly leu asn asp ala leu ser ala ala arg arg glu lys glu gln gac ggc gcg ctc ctc gac cgc ctg acc agc gag ttc ggt ctt ttt atc 1248 gcc cgt atc gaa caa atc agc gcg gtt tgg gat ttg ctc tcc act gtc 1296 ala arg ile glu gln ile ser ala val trp asp leu leu ser thr val ccc ctc gag ggt gaa gaa ccg ttg gcg aaa tgg ata acc cgc cgc gcc 1344 gac gac aaa aac gac tac att ttc aac gcc agc ccc atc agc agc gca 1392 tcc cac ctt gcc aac agc ctg tgg cgg cgt gcg gca ggc gcg gta ttg 1440 act tcc gcc acc ctg caa tcc ttg ggc aac ttc aac ctg atg ctg cgc 1488 caa acc ggg ctg caa tgg ctg ccc gaa acc acc acc ctc gcc ctc aaa 1536 agc ccc ttt gac ttt gaa aaa cag ggc gaa ctc tac atc ccc ccc ata 1584 ser pro phe asp phe glu lys gln gly glu leu tyr ile pro pro ile tac gcc agc ccc aaa gac ccc gaa gcc cac acc gcc gcc gtc atc gaa 1632 tyr ala ser pro lys asp pro glu ala his thr ala ala val ile glu tgg ctg ccc aag ctt att tcg ccc acc gaa gcc atc ggc acg ctc gtc 1680 trp leu pro lys leu ile ser pro thr glu ala ile gly thr leu val ttg ttt tcc tcg cgc aaa caa atg cag gat gtc gcc ctg cgc ctg ccc 1728 leu phe ser ser arg lys gln met gln asp val ala leu arg leu pro gga gac tac ctg ccg ctc ttg ctc gta caa ggc gaa tta ccc aaa gcc 1776 gtc ctc ctg caa aaa cac cac cgg gcc ata gaa gaa ggc aaa gcc agc 1824 val leu leu gln lys his his arg ala ile glu glu gly lys ala ser atc atc ttc gga ctc gac agc ttt gcc gaa gga ctc gac ctg ccc ggc 1872 acc gcc tgc gtg caa gtc atc atc gcc aaa ctt ccc ttc gcc atg ccc 1920 thr ala cys val gln val ile ile ala lys leu pro phe ala met pro gac aac ccc atc gaa aaa acc caa aac cgc tgg ata gaa cag cgc ggc 1968 asp asn pro ile glu lys thr gln asn arg trp ile glu gln arg gly ggc aac ccc ttc atc gaa atc acc gtc ccc gaa gcc ggc atc aaa ctc 2016 gly asn pro phe ile glu ile thr val pro glu ala gly ile lys leu atc cag gcc gtc ggc cgc ctc atc cgc acc gaa caa gac tac ggc cgc 2064 ile gln ala val gly arg leu ile arg thr glu gln asp tyr gly arg gta acc atc ctc gac aac cgc atc aaa aca cag cgg tac ggc caa caa 2112 val thr ile leu asp asn arg ile lys thr gln arg tyr gly gln gln tta ttg gcc ggc ctg ccg ccg ttt aaa agg ata ggg 2148 met leu thr asp leu glu lys asn ala ile arg asp his tyr gln asn ile gly lys asn leu pro gly phe arg pro arg ala ser gln arg glu met ile ala ala val ala asn ala phe ser arg thr leu ala arg glu gly ile met ala gln thr arg gly lys arg leu ile val ser ser ala gly arg tyr leu cys pro tyr lys leu tyr arg leu thr gln ser asn ala gln gln asn leu leu gly phe glu ala pro ala val leu trp asp glu phe ser ala arg arg phe asn gly asp arg asp thr trp pro glu lys ile asp asp ala ile trp leu lys val thr asn asp arg his gly cys leu lys thr ala cys pro asn arg pro glu cys pro phe tyr leu pro glu asn ser phe tyr cys ile asp glu ala his his leu pro lys lys ala leu ser arg phe ala ala glu his ser trp asn ile ala val ile gly leu asn asp ala leu ser ala ala arg arg glu lys glu gln ala arg ile glu gln ile ser ala val trp asp leu leu ser thr val ser pro phe asp phe glu lys gln gly glu leu tyr ile pro pro ile tyr ala ser pro lys asp pro glu ala his thr ala ala val ile glu trp leu pro lys leu ile ser pro thr glu ala ile gly thr leu val leu phe ser ser arg lys gln met gln asp val ala leu arg leu pro val leu leu gln lys his his arg ala ile glu glu gly lys ala ser thr ala cys val gln val ile ile ala lys leu pro phe ala met pro asp asn pro ile glu lys thr gln asn arg trp ile glu gln arg gly gly asn pro phe ile glu ile thr val pro glu ala gly ile lys leu ile gln ala val gly arg leu ile arg thr glu gln asp tyr gly arg val thr ile leu asp asn arg ile lys thr gln arg tyr gly gln gln atg aat atg aaa acc tta tta gca cta gcg gtt agt gca gta tgt tca 48 gtt ggt gtt gcg caa gca cac gag cat aat acg ata cct aaa ggt gct 96 val gly val ala gln ala his glu his asn thr ile pro lys gly ala tct att gaa gtg aaa gtg caa caa ctt gat cca gta aac ggt aac aaa 144 ser ile glu val lys val gln gln leu asp pro val asn gly asn lys gat gtg ggt aca gtg act att act gaa tct aac tat ggt ctt gtg ttt 192 asp val gly thr val thr ile thr glu ser 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ctt gcc gtt tcg att att ttg gtg tcg gcg gca tac att gct tcg 96 aca gag agg acg gag cgc gtc aga ccg cag cgc gtg gaa caa aat ctg 144 ccg ccg ctg tct tgg ggc ggc agc ggc gtt cag acg gca tat tgg gtg 192 cag gag gcg gtg cag ccg ggc gac tcg ctg gcg gac gtg ctg gcg cgt 240 tcg ggt atg gcg cgg gac gag att gcc cga atc acg gaa aaa tat ggc 288 ser gly met ala arg asp glu ile ala arg ile thr glu lys tyr gly ggc gaa gcc gat ttg cgg cat ttg cgt gcc gac cag tcg gtt cat gtt 336 ttg gtc ggc ggc gac ggc ggc gcg cgc gaa gtg cag ttt ttt acc gac 384 gaa gac ggc gag cgc aat ctg gtc gct ttg gaa aag aaa ggc ggc ata 432 tgg cgg cgg tcg gct tct gag gcg gat atg aag gtt ttg ccg acg ctg 480 trp arg arg ser ala ser glu ala asp met lys val leu pro thr leu cgt tcg gtc gtg gtc aaa acg tcg gcg cgc ggt tcg ctg gcg cgg gcg 528 gaa gtg ccc gtc gaa atc cgc gaa tcc tta agc ggg att ttc gcc ggc 576 cgc ttc agc ctt gac ggt ttg aag gaa ggc gat gcc gtg cgc ctg atg 624 arg phe ser leu asp gly leu lys glu gly asp ala val arg leu met tac gac agc ctg tat ttc cac ggg cag cag gtg gcg gcg ggc gat att 672 tyr asp ser leu tyr phe his gly gln gln val ala ala gly asp ile ttg gcg gct gaa gtc gtt aag ggc ggc aca agg cat cag gcg ttc tat 720 leu ala ala glu val val lys gly gly thr arg his gln ala phe tyr tac cgt tcg gac aag gaa ggc gga ggg ggc ggc aat tat tat gat gaa 768 gac ggc aag gtg ttg cag gaa aaa ggc ggc ttc aac atc gag ccg ctg 816 asp gly lys val leu gln glu lys gly gly phe asn ile glu pro leu gtc tat acg cgc att tct tcg ccg ttc ggc tac cgt atg cac ccc atc 864 val tyr thr arg ile ser ser pro phe gly tyr arg met his pro ile ctg cac aca tgg cgg ctg cac acg ggc atc gat tat gcc gca ccg cag 912 leu his thr trp arg leu his thr gly ile asp tyr ala ala pro gln gga acg ccg gtc agg gct tcc gcc gac ggc gtg att acc ttt aaa ggc 960 gly thr pro val arg ala ser ala asp gly val ile thr phe lys gly cgg aag ggc gga tac ggc aac gcg gtg atg ata cgc cac gcc aac ggt 1008 gtg gaa acg ctg tac gcg cac ttg agc gcg ttt tcg cag gcg gaa ggc 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gca agg ggc gtg gaa 432 ala pro thr pro met leu ala gln ile ala ala ala arg gly val glu ttg gac gtt ttg att gaa aaa gtt atc gaa aaa tcc gcc cgc ctg gct 480 gtt gcc gcc ggc gcg att atc gga aag cgt cag cag ctc gaa gac aaa 528 ttg aac acc atc gaa acc gcg ccc gga ttg gac gcg ctg gaa aag gaa 576 arg pro val leu thr pro pro arg pro ser asp tyr his glu trp asp leu lys asn ser leu leu ala gly tyr pro gln val glu ile asp ser ala pro thr pro met leu ala gln ile ala ala ala arg gly val glu atg ccg tct gaa aaa tgt tca gac ggc att tct tat aac ctt ttg ttt 48 met pro ser glu lys cys ser asp gly ile ser tyr asn leu leu phe gca gca cat aac caa tca gtc ttt cct att ccg ttc cga aat gca tac 96 ala ala his asn gln ser val phe pro ile pro phe arg asn ala tyr cat gcg ccc gta ccc aat att tgc gaa caa gga aag aaa atg gca cgt 144 his ala pro val pro asn ile cys glu gln gly lys lys met ala arg tta acc gta cac acc ctc gaa acc gcc ccc gaa gcc gcc aaa gcg cgc 192 gtc gag gcg gta ctt caa aac aac ggc ttt atc ccc aac ctt atc ggc 240 gta tta tca aac gcc ccc gaa gcc ttg gcg ttt tac caa gaa gtc ggc 288 val leu ser asn ala pro glu ala leu ala phe tyr gln glu val gly aag ctc aac gcc gcc aac agc ctg acc gcc ggc gaa gtc gaa gtc atc 336 cag atc atc gcc gcc cgt acc aac caa tgc ggt ttt tgc gtg gca ggg 384 cac acc aaa ctc gca acc ctg aaa aaa ctc ctg tcc gaa caa tcc gtc 432 aaa gcc gcg cgc gct ttg gca gca ggc gaa ttt gac gat gcc aaa ctc 480 ggc gcg ctc gcc gcc ttc acc caa gcc gta atg gcg aaa aaa ggc gcg 528 gta tcc gac gag gaa ctc aaa gca ttt ttc gat gcg ggc tac aac cag 576 val ser asp glu glu leu lys ala phe phe asp ala gly tyr asn gln cag cag gca gtc gaa gtc gtg atg ggc gta gcc ttg gca acc ctg tgc 624 aac tac gtc aac aac ctc gga caa acc gaa atc aac ccc gaa ttg cag 672 met pro ser glu lys cys ser asp gly ile ser tyr asn leu leu phe ala ala his asn gln ser val phe pro ile pro phe arg asn ala tyr his ala pro val pro asn ile cys glu gln gly lys lys met ala arg val leu ser asn ala pro glu ala leu ala phe tyr gln glu val gly val ser asp glu glu leu lys ala phe phe asp ala gly tyr asn gln atg ccg tct gaa aaa tgt tca gac ggc att tct tat aac ctt ttg ttt 48 met pro ser glu lys cys ser asp gly ile ser tyr asn leu leu phe gca gca cat aac caa tca gtc ttt cct att ccg ttc cga aat gca tac 96 ala ala his asn gln ser val phe pro ile pro phe arg asn ala tyr cat gcg ccc gta ccc aat att tgc gaa caa gga aag aaa atg gca cgt 144 his ala pro val pro asn ile cys glu gln gly lys lys met ala arg tta acc gta cac acc ctc gaa acc gcc ccc gaa gcc gcc aaa gcg cgc 192 gtc gag gcg gta ctt caa aac aac ggc ttt atc ccc aac ctt atc ggc 240 gta tta tca aac gcc ccc gaa gcc ttg gcg ttt tac caa gaa gtc ggc 288 val leu ser asn ala pro glu ala leu ala phe tyr gln glu val gly aag ctc aac gcc gcc aac agc ctg acc gcc ggc gaa gtc gaa gtc atc 336 cag atc atc gcc gcc cgt acc aac caa tgc ggt ttt tgc gtg gca ggg 384 cac acc aaa ctc gca acc ctg aaa aaa ctc ctg tcc gaa caa tcc gtc 432 aaa gcc gcg cgc gct ttg gca gca ggc gaa ttt gac gat gcc aaa ctc 480 ggc gcg ctc gcc gcc ttc acc caa gcc gta atg gcg aaa aaa ggc gcg 528 gta tcc gac gag gaa ctc aaa gca ttt ttc gat gcg ggc tac aac cag 576 val ser asp glu glu leu lys ala phe phe asp ala gly tyr asn gln cag cag gca gtc gaa gtc gtg atg ggc gta gcc ttg gca acc ctg tgc 624 aac tac gtc aac aac ctc gga caa acc gaa atc aac ccc gaa ttg cag 672 met pro ser glu lys cys ser asp gly ile ser tyr asn leu leu phe ala ala his asn gln ser val phe pro ile pro phe arg asn ala tyr his ala pro val pro asn ile cys glu gln gly lys lys met ala arg val leu ser asn ala pro glu ala leu ala phe tyr gln glu val gly val ser asp glu glu leu lys ala phe phe asp ala gly tyr asn gln atg aaa acc ctg ctc ctc ctc atc ccc ctc gtc ctc aca gcc tgc ggc 48 aca ctg acc ggc ata ccc gcc cac ggc ggc ggc aaa cgc ttt gcc gtc 96 thr leu thr gly ile pro ala his gly gly gly lys arg phe ala val gaa caa gaa ctc gtc gcc gca tcg tcc cgc gcc gcc gtc aaa gaa atg 144 gat ttg tcc gcc cta aaa gga cgc aaa gcc gcc ctt tac gtc tcc gtt 192 atg ggc gac caa ggt tcg ggc aac ata agc ggc gga cgc tac tct atc 240 gac gca ctg ata cgc ggc ggc tac cac aac aac ccc gaa agt gcc acc 288 asp ala leu ile arg gly gly tyr his asn asn pro glu ser ala thr caa tac agc tac ccc gcc tac gac act acc gcc acc acc aaa tcc gac 336 gcg ctc tcc agc gta acc act tcc aca tcg ctt ttg aac gcc ccc gcc 384 gcc gcc ctg acg aaa aac agc gga cgc aaa ggc gaa cgc tcc gcc gga 432 ctg tcc gtc aac ggc acg ggc gac tac cgc aac gaa acc ctg ctc gcc 480 leu ser val asn gly thr gly asp tyr arg asn glu thr leu leu ala aac ccc cgc gac gtt tcc ttc ctg acc aac ctc atc caa acc gtc ttc 528 asn pro arg asp val ser phe leu thr asn leu ile gln thr val phe tac ctg cgc ggc atc gaa gtc gta ccg ccc gaa tac gcc gac acc gac 576 tyr leu arg gly ile glu val val pro pro glu tyr ala asp thr asp gta ttc gta acc gtc gac gta ttc ggc acc gtc cgc agc cgt acc gaa 624 ctg cac ctc tac aac gcc gaa acc ctt aaa gcc caa acc aag ctc gaa 672 tat ttc gcc gtt gac cgc gac agc cgg aaa ctg ctg att acc cct aaa 720 tyr phe ala val asp arg asp ser arg lys leu leu ile thr pro lys ggc cct tac aaa gtc agc aaa acc gtc aaa gcc tca gac cgc ctg atg 816 gly pro tyr lys val ser lys thr val lys ala ser asp arg leu met gtc gat ttc tcc gac att acc ccc tac ggc gac aca acc gcc caa aac 864 val asp phe ser asp ile thr pro tyr gly asp thr thr ala gln asn cgt ccc gac ttc aaa caa aac aac ggt aaa aaa ccc gat gtc ggc aac 912 thr leu thr gly ile pro ala his gly gly gly lys arg phe ala val asp ala leu ile arg gly gly tyr his asn asn pro glu ser ala thr leu ser val asn gly thr gly asp tyr arg asn glu thr leu leu ala asn pro arg asp val ser phe leu thr asn leu ile gln thr val phe tyr leu arg gly ile glu val val pro pro glu tyr ala asp thr asp tyr phe ala val asp arg asp ser arg lys leu leu ile thr pro lys gly pro tyr lys val ser lys thr val lys ala ser asp arg leu met val asp phe ser asp ile thr pro tyr gly asp thr thr ala gln asn atg agc gcg ccc gac ctc ttt gtc gcc cac ttc cgc gaa gcc gtc ccc 48 met ser ala pro asp leu phe val ala his phe arg glu ala val pro tac atc cgc caa atg cgc ggc aaa acg ctg gtc gcc ggc ata gac gac 96 tyr ile arg gln met arg gly lys thr leu val ala gly ile asp asp cgc ctg ctc gaa ggt gat acc tta aac aag ctc gcc gcc gac atc ggg 144 ctg ttg tcg caa ctg ggc atc agg ctc gtc ctc atc cac ggc gcg cgc 192 cac ttc ctc gac cgc cac gcc gcc gct caa ggc cgc acg ccg cat tat 240 his phe leu asp arg his ala ala ala gln gly arg thr pro his tyr tgc cgg ggc ttg cgc gtt acc gac gaa acc tcg ctc gaa cag gcg cag 288 cys arg gly leu arg val thr asp glu thr ser leu glu gln ala gln cag ttt gcc ggc acc gtc cgc agc cgt ttt gaa gcc gca ttg tgc ggc 336 gln phe ala gly thr val arg ser arg phe glu ala ala leu cys gly agc gtt tcc ggg ttc gcg cgc gcg cct tcc gtc ccg ctc gta tcg ggc 384 aac ttc ctg acc gcc cgt ccg ata ggt gtg att gac gga acc gat atg 432 asn phe leu thr ala arg pro ile gly val ile asp gly thr asp met gaa tac gcg ggc gtt atc cgc aaa acc gac acc gcc gcc ctc cgt ttc 480 glu tyr ala gly val ile arg lys thr asp thr ala ala leu arg phe caa ctc gac gcg ggc aat atc gtc tgg ctg ccg ccg ctc gga cat tcc 528 gln leu asp ala gly asn ile val trp leu pro pro leu gly his ser tac agc ggc aag acc ttc tat ctc gat atg ctt caa acc gcc gcc tcc 576 tyr ser gly lys thr phe tyr leu asp met leu gln thr ala ala ser gcc gcc gtc tcg ctt cag gcc gaa aaa ctc gtt tac ctg acc ctt tca 624 gac ggc att tcc cgc ccc gac ggc acg ctc gcc gaa acc ctc tcg gca 672 cag gaa gcg caa tcg ctg gcg gaa cac gcc ggc ggc gaa acg cga cgg 720 ctg att tcg tcc gcc gtt gcc gcg ctc gaa ggc ggc gtg cat cgc gtc 768 caa atc ctc aac gga gcc gcc gac ggc agc ctg ctg caa gaa ctc ttc 816 acc cgc aac ggc atc ggc acg tcc att gcc aaa gaa gcc ttc gtc tcc 864 thr arg asn gly ile gly thr ser ile ala lys glu ala phe val ser atc cgg cag gcg cac agc ggc gac atc ccg cac atc gcc gcc ctc atc 912 cgc ccg ctg gaa gaa cag ggc atc ctg ctg cac cgc agc cgc gaa tac 960 ctc gaa aac cac att tcc gaa ttt tcc atc ctc gaa cac gac ggc aac 1008 ctg tac ggt tgc gcc gcc ctg aaa acc ttt gcc gaa gcc gat tgc ggc 1056 gaa atc gcc tgc ctt gcc gtc tcg ccg cag gca cag gac ggc ggc tac 1104 glu ile ala cys leu ala val ser pro gln ala gln asp gly gly tyr ggc gaa cgc ctg ctt gcc cac att atc gat aag gcg cgc ggc ata ggc 1152 ata agc agg ctg ttc gca ctg tcc aca aat acc ggc gaa tgg ttt gcc 1200 ile ser arg leu phe ala leu ser thr asn thr gly glu trp phe ala gaa cgc ggc ttt cag acg gca tcg gaa gac gag ttg ccc gaa acg cgg 1248 glu arg gly phe gln thr ala ser glu asp glu leu pro glu thr arg cgc aaa gac tac cgc agc aac gga cgg aac tcg cat att ctg gta cgt 1296 arg lys asp tyr arg ser asn gly arg asn ser his ile leu val arg met ser ala pro asp leu phe val ala his phe arg glu ala val pro tyr ile arg gln met arg gly lys thr leu val ala gly ile asp asp his phe leu asp arg his ala ala ala gln gly arg thr pro his tyr cys arg gly leu arg val thr asp glu thr ser leu glu gln ala gln gln phe ala gly thr val arg ser arg phe glu ala ala leu cys gly asn phe leu thr ala arg pro ile gly val ile asp gly thr asp met glu tyr ala gly val ile arg lys thr asp thr ala ala leu arg phe gln leu asp ala gly asn ile val trp leu pro pro leu gly his ser tyr ser gly lys thr phe tyr leu asp met leu gln thr ala ala ser thr arg asn gly ile gly thr ser ile ala lys glu ala phe val ser glu ile ala cys leu ala val ser pro gln ala gln asp gly gly tyr ile ser arg leu phe ala leu ser thr asn thr gly glu trp phe ala glu arg gly phe gln thr ala ser glu asp glu leu pro glu thr arg arg lys asp tyr arg ser asn gly arg asn ser his ile leu val arg val asp thr glu ala pro arg pro ala pro lys tyr gln asp val phe met arg leu lys arg arg asn trp tyr pro gln ala lys glu asp glu val lys leu asp glu ser asp trp glu ala thr gly leu pro asp glu gln ala lys asp tyr glu asn phe lys tyr val tyr ser gly trp phe tyr lys his ala lys arg glu phe asn leu lys val glu pro lys ser ala lys asn gly asp asp gly tyr ile phe tyr his gly lys glu pro ser arg gln leu pro ala ser gly lys ile thr tyr lys gly val trp his phe ala thr asp thr lys lys gly gln lys phe arg glu ile ile gln glu gly tyr gly phe thr ser asn leu glu val asp phe his asn asn ser glu thr lys glu his pro phe val ser asp ser ser ser leu leu lys tyr gly met leu thr arg lys asn ser lys ser ala met gln gln ser met phe leu gln gly glu arg thr asp glu lys glu ile pro ser glu gln asn ile val tyr arg gly ser trp tyr gly tyr ile ala gly asn arg ala glu phe thr val asn phe ala asp lys lys ile thr gly thr leu thr ala asp asn arg gln glu ala thr phe thr ile asp ser gly phe asp leu asp gln ser asn thr thr arg thr pro lys ala tyr ile thr asp ala lys val gln gly gly phe tyr gly pro lys ala glu glu leu gly gly trp phe ala tyr pro gly asp lys gln thr lys ala ile gly val tyr gly ser leu gly arg gln thr asp gly pro tyr ser his glu trp thr thr gly glu trp lys val glu val asn phe asp pro leu thr his gly gln phe phe ser ile leu pro ile tyr asp ser gln thr phe his asp ala ile cys ala leu ile val glu glu leu phe glu tyr ala gly lys trp arg asn ile arg val gln gly pro thr thr ile gly leu his his arg ile cys tyr thr thr ser ala ser val leu thr glu ala val lys gln ser asp leu pro ser gly tyr asp his leu cys gln phe val met ser gly gln leu ser asp ser glu lys leu leu glu ser leu glu asn phe trp asn gly ile gln glu trp thr glu arg his gly tyr ile val asp val ser lys arg ile pro phe