GRA1_GIBZE
ID GRA1_GIBZE Reviewed; 7839 AA.
AC A0A098D1P1; A0A0E0RKU6;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 1.
DT 23-FEB-2022, entry version 43.
DE RecName: Full=Nonribosomal peptide synthetase GRA1 {ECO:0000303|PubMed:30395461};
DE EC=6.3.2.- {ECO:0000269|PubMed:30395461};
DE AltName: Full=Gramillins biosynthetic cluster protein 1 {ECO:0000303|PubMed:30395461};
DE AltName: Full=Nonribosomal peptide synthetase 8 {ECO:0000303|PubMed:26693688};
DE Short=NRPS8 {ECO:0000303|PubMed:26693688};
GN Name=GRA1 {ECO:0000303|PubMed:30395461}; Synonyms=NRPS8;
GN ORFNames=FG00042, FGRAMPH1_01T00143, FGSG_15673;
OS Gibberella zeae (strain ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084
OS / PH-1) (Wheat head blight fungus) (Fusarium graminearum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=229533;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=17823352; DOI=10.1126/science.1143708;
RA Cuomo C.A., Gueldener U., Xu J.-R., Trail F., Turgeon B.G., Di Pietro A.,
RA Walton J.D., Ma L.-J., Baker S.E., Rep M., Adam G., Antoniw J., Baldwin T.,
RA Calvo S.E., Chang Y.-L., DeCaprio D., Gale L.R., Gnerre S., Goswami R.S.,
RA Hammond-Kosack K., Harris L.J., Hilburn K., Kennell J.C., Kroken S.,
RA Magnuson J.K., Mannhaupt G., Mauceli E.W., Mewes H.-W., Mitterbauer R.,
RA Muehlbauer G., Muensterkoetter M., Nelson D., O'Donnell K., Ouellet T.,
RA Qi W., Quesneville H., Roncero M.I.G., Seong K.-Y., Tetko I.V., Urban M.,
RA Waalwijk C., Ward T.J., Yao J., Birren B.W., Kistler H.C.;
RT "The Fusarium graminearum genome reveals a link between localized
RT polymorphism and pathogen specialization.";
RL Science 317:1400-1402(2007).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=20237561; DOI=10.1038/nature08850;
RA Ma L.-J., van der Does H.C., Borkovich K.A., Coleman J.J., Daboussi M.-J.,
RA Di Pietro A., Dufresne M., Freitag M., Grabherr M., Henrissat B.,
RA Houterman P.M., Kang S., Shim W.-B., Woloshuk C., Xie X., Xu J.-R.,
RA Antoniw J., Baker S.E., Bluhm B.H., Breakspear A., Brown D.W.,
RA Butchko R.A.E., Chapman S., Coulson R., Coutinho P.M., Danchin E.G.J.,
RA Diener A., Gale L.R., Gardiner D.M., Goff S., Hammond-Kosack K.E.,
RA Hilburn K., Hua-Van A., Jonkers W., Kazan K., Kodira C.D., Koehrsen M.,
RA Kumar L., Lee Y.-H., Li L., Manners J.M., Miranda-Saavedra D.,
RA Mukherjee M., Park G., Park J., Park S.-Y., Proctor R.H., Regev A.,
RA Ruiz-Roldan M.C., Sain D., Sakthikumar S., Sykes S., Schwartz D.C.,
RA Turgeon B.G., Wapinski I., Yoder O., Young S., Zeng Q., Zhou S.,
RA Galagan J., Cuomo C.A., Kistler H.C., Rep M.;
RT "Comparative genomics reveals mobile pathogenicity chromosomes in
RT Fusarium.";
RL Nature 464:367-373(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=26198851; DOI=10.1186/s12864-015-1756-1;
RA King R., Urban M., Hammond-Kosack M.C.U., Hassani-Pak K.,
RA Hammond-Kosack K.E.;
RT "The completed genome sequence of the pathogenic ascomycete fungus Fusarium
RT graminearum.";
RL BMC Genomics 16:544-544(2015).
RN [4]
RP INDUCTION.
RX PubMed=26693688; DOI=10.1016/j.funbio.2015.10.010;
RA Harris L.J., Balcerzak M., Johnston A., Schneiderman D., Ouellet T.;
RT "Host-preferential Fusarium graminearum gene expression during infection of
RT wheat, barley, and maize.";
RL Fungal Biol. 120:111-123(2016).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, AND PATHWAY.
RX PubMed=30395461; DOI=10.1021/jacs.8b10017;
RA Bahadoor A., Brauer E.K., Bosnich W., Schneiderman D., Johnston A.,
RA Aubin Y., Blackwell B., Melanson J.E., Harris L.J.;
RT "Gramillin A and B: cyclic lipopeptides identified as the nonribosomal
RT biosynthetic products of Fusarium graminearum.";
RL J. Am. Chem. Soc. 140:16783-16791(2018).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of gramillins A and B, bicyclic
CC lipopeptides that induce cell death in maize leaves but not in wheat
CC leaves (PubMed:30395461). The nonribosomal peptide synthetase GRA1
CC incorporates respectively a glutamic adic (Glu), a leucine (Leu), a
CC serine (Ser), a hydroxyglutamine (HOGln), a 2-amino decanoic acid, and
CC 2 cysteins (CysB and CysA) (Probable). The biosynthesis of 2-amino
CC decanoic acid incorporated in gramillins could be initiated by a fatty
CC acid synthase composed of the alpha and beta subunits FGSG_00036 and
CC FGSG_11656 (Probable). The cytochrome P450 monooxygenase FGSG_15680
CC could hydroxylate the fatty acid chain (Probable). Subsequent oxidation
CC to the ketone by the oxidoreductase FGSG_00048 and transamination by
CC aminotransferase FGSG_00049 could form 2-amino-decanoic acid
CC (Probable). On the other hand, FGSG_15680 could also be responsible for
CC the HO-modified glutamine at the gamma-position (Probable). Whether
CC hydroxylation occurs on the fully assembled product or on the Gln
CC residue prior to assembly into the gramillins requires further proof
CC (Probable). The thioredoxin FGSG_00043 could also be required for the
CC disulfide-bond formation between CysA and CysB (Probable). The specific
CC involvement of the remaining proteins from the cluster is more
CC difficult to discern, but could have broader regulatory (FGSG_00040 and
CC FGSG_11657) or enzymatic functions (FGSG_00044 and FGSG_00045)
CC (Probable). The final C-domain of GRA1 does not possess the expected
CC sequence of a termination CT domain, often implicated in
CC macrocyclization and release of a cyclopeptidein fungal NRPs; and the
CC thioesterase FGSG_00047 may act in concert with the terminal C-domain
CC of GRA1 to catalyze the formation of the macrocyclic anhydride and
CC release of the products (Probable). {ECO:0000269|PubMed:30395461,
CC ECO:0000305|PubMed:30395461}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:26693688}.
CC -!- INDUCTION: Expressed during infection of maize kernels and exhibits
CC transient expression during barley and wheat spike infection
CC (PubMed:26693688). Coexpressed alongside the trichothecene biosynthesis
CC gene cluster (PubMed:26693688). {ECO:0000269|PubMed:26693688}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module. Each module is responsible for the recognition (via the A
CC domain) and incorporation of a single amino acid into the growing
CC peptide product. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC epimerase (E) domains (responsible for L- to D-amino acid conversion)
CC are present within the NRP synthetase. GRA1 has the following
CC architecture: A-T-C-A-T-C-A-T-C-A-T-C-A-T-C-A-T-C-A-T-C.
CC {ECO:0000305|PubMed:30395461}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of gramillins A and B.
CC {ECO:0000269|PubMed:30395461}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; HG970332; CEF71871.1; -; Genomic_DNA.
DR SMR; A0A098D1P1; -.
DR STRING; 5518.FGSG_11659P0; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G00143; -.
DR eggNOG; KOG1176; Eukaryota.
DR eggNOG; KOG1178; Eukaryota.
DR Proteomes; UP000070720; Chromosome 1.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 7.
DR Gene3D; 3.30.300.30; -; 7.
DR Gene3D; 3.30.559.10; -; 8.
DR Gene3D; 3.40.50.12780; -; 7.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 7.
DR Pfam; PF00668; Condensation; 7.
DR Pfam; PF00550; PP-binding; 7.
DR SMART; SM00823; PKS_PP; 6.
DR SUPFAM; SSF47336; SSF47336; 7.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 7.
DR PROSITE; PS00455; AMP_BINDING; 6.
DR PROSITE; PS50075; CARRIER; 7.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 2: Evidence at transcript level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..7839
FT /note="Nonribosomal peptide synthetase GRA1"
FT /id="PRO_0000450560"
FT DOMAIN 793..866
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1880..1957
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2963..3040
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 4057..4134
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 5113..5189
FT /note="Carrier 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 6207..6282
FT /note="Carrier 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 7290..7366
FT /note="Carrier 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..650
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 916..1332
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 1351..1742
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 1997..2413
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 2432..2828
FT /note="Adenylation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 3084..3496
FT /note="Condensation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 3520..3923
FT /note="Adenylation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 4234..4569
FT /note="Condensation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 4591..4982
FT /note="Adenylation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 5224..5653
FT /note="Condensation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 5671..6069
FT /note="Adenylation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 6321..6730
FT /note="Condensation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 6756..7147
FT /note="Adenylation 7"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT REGION 7404..7704
FT /note="Condensation7"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30395461"
FT COMPBIAS 8..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 827
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1918
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3001
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4095
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 5150
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 6243
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 7327
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 7839 AA; 863791 MW; ACF11A5B8B677BF0 CRC64;
MALLNGKSTL PNGHNSSIES PNGYTEHEMP IPSDWQRYLI DIDHAAVSLF KSPRPDDPVA
TVKSTHRFVL TEETLLVSIP STIYAAFAIV MSEYSNSQDV LFGVRAESRV VPFRVLVDKN
DQISSFLDQV ASKWKMAQNF PPDMPVPAVP NVLAFVDDKM SASGNGLVLE ENEEISMVIS
LDSKEITIQV LFNPACADLV AVQRFLKQLE TVFHQLCKPS AGQLIKEVKS ITADDIRDMT
TWNSASMTPY TPECIHDVVK QHVLASPNSC AVHGWDGDLS YVQLDEESSR LANYLYRKGV
RPHDLVPLAF YKSIWFTICA LALSKLGAAI VPLDPQWPKD RQMYIINDIE SSRIITNIPN
SASAYAGLEI IDISQLSLAN EPATARYPVT PEHAIYAYYT SGTTGQPKGC VIEHGAFVSS
SSKRIKFMGR NKDSRLLQVT TYTFDVAMDD IFFTLMAGGC LCVPTREECL NDIVGAVEKY
NCNTLHVAPS LARDLQPSQL PSLRTLILGG EAMSANILRT WAGRVGLYNS YGPTECCIAC
CVNLIQSADE NPRNIGRPID CSYWLVRPGD IDTLAAIGTV GEILIHGPNL GRGYLNKPEL
TAKAFPQNIS WASEVGLPAE ARFYRTGDLA RFNADGSVCL LGRIDDQVKI HGQRIELGEI
DYRLSQCLPA GIEAISGVVN FRDREVATLV AFIQTVNSDS NSAKSSGSLA LADTDNWNQF
HRLRSHVMEQ LSHNLPSYMV PSVFLPVQNF LYFNQGKLNR RGMFQQASRF RLDDILTINT
SAGHKADDTS SWSAEALVLR QLWAIALGLE EKNIHLDSRF ADLGGDSLAA IRLGILCRPY
DIELSVDDIL QQSTILLQAE MSEKKKKQNI EKHEVAQEAI LPAGQRFGLL GQDVDVGMLC
EQTSAQCHID SGAIDDIYPA SPLQESLMAL SMDDSPYISQ FVFRLPDNLD MYRFRKAWKS
TFSDIPILRT RIIYLQDFGT LQVVVDEDIE WTEHKNITLS QFLKDDQERL MQVGDRLVRF
TIVQESPGTS FLVWTCHHAC HDGRTVDQTL RVVGAKYLDR PVSSPVPYRY YIQFQQDVYR
RDWQEYWTRN LAGASVSAFP AQDKAVHQPV TDASHQYSFS MPRISTERSD TSVFSPSSIL
RAAWALIVSR YEESEDVTFG TIVGANASTI ADADAIVGPT NNTIPVRVLA SEGWTVEAFV
SHVKQQFEYS PFQHVGLANL KDLSPEMQDI VNIRNIFVVQ SHFVGQTGSE MNLERVAVSA
HEGFKYPLVV ECFQENASQV LVNFIYDSHI LDQSQISRLA LQLENTINLL VHNPHKTLNQ
IEILSPSDVA QILEWQADMP SPSSLCLHQQ FFTQVKRSPD AIALCTWEGQ FTYLEVQNLV
ESMAIYLQDA GVRRGDRILC QIEKSACAVI SFLAILKLGG TCVLLGTTWP RIRSEVIAED
TKAQYLLVSP TLSNALISLV PNILEVSTSF IQRLPRPTQY VDSVYQPSDL AFILFTSGST
GTPKGVQLAH SGLVTNFASM AQHMQYTSET RLFQFSDFTF DLSIYDIFGM LMVGGCICMP
SEQERHEDLM GSMNRMKVNT VTATPSIAKM IKPSSVPTLR CIKLGGEALD STTLATLAGS
LDTENGYGVT ECSVWSTCTD RLSPDADPRN VGRGINCYTW IVDAKNPNRL RPIGAVGELI
LQGPGVALGY VNKPEESKRV FLDALPWSTD KGRSYRTGDL VKYAPDGSLI YVQRKDAQLK
IRGQRFESSE VESHLQQCGL PEGNFCVDLV KTQTGPVVVV FLCMNKEVEM KDASKLGVVP
LDQQDSSIVD QMAQAMRMLI PRLPGYMIPQ AVIPVTQMPV SNSGKLDRRA LRSLADGMSP
GQLRQLLRPS EDSIYHKRTE LETEAERTMA VLWSQVLAID DSHVFHTDDD FFQLGGHSIA
LMRLISAGKG HGMSISYRDA FLHPSLGAMS RQATVSDAEE HALPRLIQPF AMAPSDVDGL
IQESSRACQV DPQDIVDLYP CTPFQESTMT LSLSKPGLYT AQFVWSLPDT IDLARLRSAW
ETLVRSDAIL RTRLIYSSKY WQVVTRTGID FALADMSIDS YLEEDKARPI RLGQPLNRLA
IIQDQTSATQ YLAWTAHHST YDGHSWSSIQ DRLSDLYTQG GSKLPLVPYN VFVDHIVNNP
LPETGLSFWK DMMSGARMPS FPKLPLNNDL QSTNSVVTQS VSLPRQTSSD VTVASAIQGA
WAILLGQYEN SDDVLFAATL SGRNVPVDGI ENIAGPTSCT VPMRVRTDPG QSTRSWLRSV
QQSYVDAATY GQIGMNEISL VNKDAEVARH IRSLLIVQAI TSKTVSGLER IGCTKIETKA
KGFLSYALVV ECKPSMENNE MEVMVSYDAN LLDGPSVYRL VWQLEFTLQQ LLSDNCKTIR
DLCLISPSDM ETISTWNKEL PKTVETTVHA LFDRRLSQKH SATAISSWDG EMTYVELDNY
SSSLAAHLMA SGVKPGQYIP LCFEKTMWMV VSMLAVLKAG GACVSLDPNH PSRHHQVILS
RVSADIVITS PANKHRFPGN RVLSVSAALM TKIAHEPYAA PLVSAHQPAF VVFTSGTTGE
PKGIILEHRA LCTSIEAHGQ FMEFGPESRV LQFASYTFDV SIAEMLTTLA FGGCICIPSD
HARLNNLSGA IKTLRVNQAY LTASVAALLD PDTLNGSLKV LSVGGEQVGQ EVLTRWGDRT
KLLNMYGPAE TTIWCGGKHS VKPDGDAANI GYGVGARMWL TDVNDVQKLA PIGAVGEIVI
EGPLLARGYI NGNNDVFVES PDWAKAFNVF DGFDQVTGRV YRSGDLGRYQ SDGSIAICGR
RDTQLKIRGQ RVEVSQIEDQ LQRLAPDFKC VVGVLRTDTP TLVAFIGLEG PTKDQGLTDS
MDLVVRTRDL SEEVRDLMGS LESRLANILP PYSVPAHYLV LRNIPLMTSG KTDRKKLQVI
ASEHLEHSVD ASKPQMLQQV KKIPTTQMEW NLFGLWAQVL GINNLASLGT DDNFFRCGGD
SLKAMQLASL ASQRGITLQV SDLFKNPVLA DLAQAIVLDT PKEIETSPVQ DIPDPYSLLP
NDTKEQVQAQ AALDCDVSPN LIDDIYPCTP LQDGLFALSQ KQPGAYVAQF KFSVANRINI
RRLRQAWETV CDQAPILRSR LVSTPSGIVQ VVLTEDFWWY ERHDIDTSAE LEQDKAAIGG
LGQPLQRFRL VQDVARGQKT LVWTIHHAAF DGWSIERILE SVRLVYQDQP IPNPYVPFNA
FIRYSSGIVE NHESKEFWQS YLSNITPPTF PALPSPSYQA LADTVIESKM SNLKLPDSFT
LTSILRAAWA IVVSTYQGSD DVVFLTTVFG RNAPLAGIDK IIGPTITTIP IRVKLNDPST
TVDMLLQAVQ ESATETMAFE QLGLQSIRNL NADCKAACMA QNLLVIQTSR GEDATVPFGG
FEKLPDETKG FSTIPFTLEC TATSEGGLSI EASFDSKIVD PAQANRIIKT FEHVTQQMCH
KHLKLNQVDL ISDSDHDLIR NWNSTMPCAK EECIHHRLDR LAVSNPDAEA VCAWDGIFTF
KELNSLSNRY AVYLQSQGIK PGNIVPFCFD KSKWVVVAML AIMKVGAASV TVDPKHPPGR
RDGILSAVSA SAVVTTSGYT HLFDHNASHG LKTLVLDGKT MDSIADSLQP ADIESTPNDA
AFVVYTSGST GTPKAVVIEH RGICTGAFHL AKLIHLGPQT RCLQFAAFTF DQSFGDIFHT
LLLGGCVCIP SESDRLNDLV GSILRLRANT AILTPTVACS IDPSELGSHK MDVLTVGGEP
VTAEAIRTWA PHVRLFNTYG PAECSVTTIG RPINMQNVTQ PANIGRGLGA LVWLTYPDDP
ERLTPIGTVG EILMEGPQLA RGYLNDSRNT NAAYITDPAW SHRFPVPGMS TPRRFYRTGD
LGQYQADGTI VCLGRRDSQV KLRGQRMELG EVEHHISTYS QSALEIIADV FTPPNGTATL
AACISLKGYE TKGDECQVEV DEQVLTIFSA MLSGLDSYLS RMLPAYMIPT LYVPVTHIPL
TPSGKKDRKS IRLMLARITV DQVQKMRTIL GESEPSRPLT EREKDLQQLW VKVLKLDGET
VINANTNFFH SGGDSVRAMA LVAAARRKGT HLTVAEIFSH PKLCDMAAMT TSLSQKGQPV
QLAPYSLLRS TPSADTMSEA CGACGVDHSQ IQDMYPTTPL QQALVALSIK DSGAYVSNFV
FLLPSHLDVE LFQRAWECVY VVVSEKVRWN YGDNLEEFVG RQSQKGFKLG QRMAESAIVR
QKDGKTFFIL ILHHAIYDGW SLRRLLEAAE QIYHGQAIPR FVIFNHFVAH VSRSEDNRAP
AFWRSYLEGL PKTSFIQQPT TAYKPTADHI ISQDVSLRDN FTARSGVTIT SLMRAAWAMV
LATYNSDQTP DVVFGTVVGG RSLDLADIEY IDGPTIATVP FRVTFDPTAP VDMLLQSVQT
MSTQILQHEQ FGVQNIIKVS DDGRLACDFE TLLVVQDSAE IKASSGFLDM DNIYQRPDRP
PGIPLVVECS PSAGNLHLEI HFDAKLLEET QAKRLIRQLA HVIKQLANSV PSLSLSCIDM
MNPDDAEEIK SWNKKPPPTF DGCLHEMVLQ HSKGCPDRIA IQSWDTSLTY SELDHLSSIL
AQYLNSLGVR PEDKVPFCMD KSAFAIVAML AILRSGGCFV PLDMSSPTKR LKNIIKRVNA
KFILVSPKTR PLFEDVEGQL VEVTKSMIDG LPELSKSLYI PSATHPAYVL FTSGSTGTPK
GVVVEHGAIA TSVSSFSSYL GFNPDVRVLQ FAPYVFDVSI GEIFACLVSG GCLCIASESS
LMDDLPLCIQ QLDVNFAVLT PTFARTLTPS EVPSLKTLVL GGEPLRKRDV ETWATTVRLF
NGYGPTEASV LAMAYRVPDS QSPCNLIGLS VGCRSWIVSP SDPNILPPIG AVGELVLEGN
TLARGYLDTE SAQGAFIEDP KFLDSLVPEA TGSRVYKTGD LVRYNAEGIV EFVSRKDTQV
KFHGRRIELE DIEHNAMEAM PEAKHLVVEL VRLGNSQQEA LALFFHTDNQ RTANEKDPIL
PIGQDLVARL RGVKSNLAVT LPSYMVPSLY IPLSTWPSTS NGKVNRHLLR NLVLHFTSEA
AAAYSLHTGD SSALSSDEES QLAQLWATTL NIDARTIGSS DSFFQHGGDS IAAVRLVTLA
REQGIGLSVD TLLSKPILRD MALCMTSAQP VRETIVRPFN QIHSHQEEVL LAASQFGVEP
AMIEDIYPCS ALQNSLMAVS LKNSSAYLSQ FVVAIPEGLD IDVLQAAWNT VYSDSPILRT
RFYQPSLNNM QHPILQAVVD QKPIWGTEEN LDEFLGRDKQ TPTGLGSPLT RFTIVVDKTN
QERLFVLTAH HAIYDGWSIA STFEKVDMIL KGIALPKSVG YNIFIHHLQS LNTQENKAFW
SSTLEGATQT LFPQLPSHSY EPATDNSLKH QFAYPADLAP HSTVTMATIV RGAWGLLVSK
YCDSPDVVFG TTVNGRMAPI PGIEMVQGPT MATIPFRTRI STNQSVLSYL EQLHVQQIES
IPHEQYGLQN IKHLSEPIAR VCEFQNLLVI QSSRDSSLSD SGFAFGTVKN MDQGSFSMQG
FHNMALVVEC SIDSEVIHVT LNFDSNVIPK TQVQRIAHHF EHLILQLQAG STEPDLKIDQ
IDHVSPSDQA EILEWNSSIP GSVLCCVHEL FESRARLQPS APAICARDGQ LTYFELQAKA
TTLAAYLSLQ GLGRGVLVPL LFEKSCWAVV AMMAVLKAGA ANVALNPEHP QARLEDSINA
TQGEVILCSR KHFELASSFD MQVIVVDEDL FHHIDLPSLA SSDPWSPTYP AGPDDPCFVL
FTSGTTGKPK GIVINHAAMC SSINGHSSTL RYSTGPGSRN FQFTAYTSDV SIGEIFTSLA
VGSCVCVPSD YDRMNNLAGS MRDLNVTWAF LTPSVAALLK PEEVPCLRTL LFGGETATPE
NISTWADSLY LINSAGPAEC CIWTHCNPGI STADIGSNWG YNLGCATWIT DPNNPSVLMP
IGVTGEMLIE GPNLAQGYLN DPERTQKSFV EIYLAGKKRR LYRTGDLARF MADGKTQFLG
RRDTQVKLRG QRVEIGEIEN QIRRHIPDST LVAVEMVRIA EGKSAPLLAA FHAPKDPRAI
DDTGDTPQAE VLSAAMVQEL GVILDELAAK LAETLPQHMI PTAFIPLTSM PLTASAKTDR
NVLSALASTI SVEQLSYYAL TSAEKQFPSS LAEQQMAKLW QEVLNTKIDI GIHDSFFRIG
GDSISAMHLV SRSRAVGISL TVEQIFKNPT LQHMAAIATT FTESMGSTTV EPFSLISPTV
TFDIVCSEAQ EQCQVTAQQI QDIYPCSALQ EGLLALSLKT AGSYLAQMVF EIPDELDLER
FKDAWAHMVA KAAPILRTQF FESPSQGHQL MQAVIDAPLE WTYSDKLDEY LMTDSTKIVQ
LGQPTSRYAI ISNTQRYFVF TAHHAVYDGA SLGPMFEAVE KIYSENYVSS SSPYSLFVQY
LLGMDSDSSK AYWEMSLQGA SAPTFPRLPS IGYRPMTNDA LKRTIALPAR HDTEFTMSSI
ARAAWSLVVA SYSDTDDIVF ASTVGGRTLP IAGIENIIGP TLATVPVRVT IDRTASVSDF
LTMIQEQSTS MMPHEQYGLQ NIKRISPSVS AASDLHNLLV INTSSVEGLG SGGLGLKQVD
LGRADGFHNF ALSIECTAEA DALSLAVSFD DHVIDPRQIR RVVNQFEHML QQLSTCAIHT
RLADMDLTGP ADIAEIHLWN SHVPPPQQNY VHTLVEQRVK SQPDSPAVCS WEGELTYREL
DELSSSLANH LITAFAVAPG TLIPILFEKS IWTVVTMLAV LKAGGANVPM DPQQPLARLQ
ELAADIGASL AISSSKYQDK AQNVTARSMF VDREVLTTIE KTPICPASTV SYEDPAFILF
TSGSTGKPKA ILIDHTAFTS SIKGHGEILR YRKGSRNLQF TAYISDVSIG EIFTSLSAGA
CVCVPSDFER MNDLAGSINR MRVDWAFLTP SVASLLDATK VPSLKTLVFG GETATPENIA
AWAPRLFLIN SFGPAECSIW THCDPGVGIT HNGSHIGYAI GCATWIVDPN DYNKLAPIGS
IGELIVEGPN VARGYLDEAK TKEAFLKTAA WMPSGRKNRL YKMGDLVRYL PDGKIQFLGR
KDSQIKLHGQ RIELGEIEHQ LRVALAKHDA DRNVQVAVEM VSLSTDTSTS SLLTAFVDYE
GISSDDGPAQ LSSGEKAQQW ARQMFRVAHE HLALTLPRHM IPSVLLPLTR MPLNGSAKTD
RKVLKQIVSG MDTMQRALYS LARVETNIIK AATPNEKTLH HIWSEILSIS PESFGVEANF
MSLGGDSIAA MKLIPIAQAA GLSISVEDLF TRPVLHDLAR VSRQSITEHS QDIPPFYIME
QAQNQDELLA EASTHCNLPP DAIHDIYPCT QVQERFISTT QIQPGAYTLQ DVFKISSDMD
LAQFKKAWTR TVASHVALRT RIFLSNDRHQ HLQVVQKASE TLDWIHSENL EEYLKADKAK
SMEYGGSLVR SAIVSEGVER HFVVTYHHSI YDAVSLGIIM NDLEAFYLDD LYEVNEPKYN
AFVHHLTQVK SQELSSQFWR DHLAGDRSTI TPLYQPVDGA RVDSLLRHTI TFPMHYQQSQ
LSLTVAAFTY AALSLVTARL TGSSSAVLEL TLLGRSVPVK GIERMVGTTV TSAPLRIDTT
AGNDKPWTVT VEDYLDYAKK RASSIVLHEH TSMPDPETKH ITSAALPIVV HPSNPHKEAL
GTGIGLQRHE IQSMGQNSSA FYMDIAALDG EGLEINLPFD MPLDEVTRNV DHETDLRMCD
IIEQEFRGYI ILALVNRLNF VPSCWTMGRW LNEAPRSTY
