NRPS4_GIBZE
ID NRPS4_GIBZE Reviewed; 7639 AA.
AC I1RF49; A0A098D813;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Nonribosomal peptide synthetase 4 {ECO:0000303|PubMed:22862913};
DE Short=NRPS 4 {ECO:0000303|PubMed:22862913};
DE EC=6.3.2.- {ECO:0000269|PubMed:34292732};
DE AltName: Full=Fusahexin biosynthesis cluster protein NPRS4 {ECO:0000303|PubMed:34292732};
GN Name=NRPS4 {ECO:0000303|PubMed:34292732};
GN ORFNames=FG02315, FGRAMPH1_01T05575;
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 FUNCTION, DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=22862913; DOI=10.1016/j.funbio.2012.04.014;
RA Hansen F.T., Droce A., Soerensen J.L., Fojan P., Giese H.,
RA Sondergaard T.E.;
RT "Overexpression of NRPS4 leads to increased surface hydrophobicity in
RT Fusarium graminearum.";
RL Fungal Biol. 116:855-862(2012).
RN [5]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=34292732; DOI=10.1021/acs.jnatprod.0c00947;
RA Westphal K.R., Bachleitner S., Severinsen M.M., Brundtoe M.L., Hansen F.T.,
RA Soerensen T., Wollenberg R.D., Lysoee E., Studt L., Soerensen J.L.,
RA Sondergaard T.E., Wimmer R.;
RT "Cyclic, hydrophobic hexapeptide fusahexin is the product of a nonribosomal
RT peptide synthetase in Fusarium graminearum.";
RL J. Nat. Prod. 84:2070-2080(2021).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of the fusahexin, a cyclic hydrophobic
CC hexapeptide with the amino acid sequence cyclo-(D-Ala-L-Leu-D-allo-Thr-
CC L-Pro-D-Leu-L-Leu) that plays an important role in cell surface
CC hydrophobicity (PubMed:22862913, PubMed:34292732). Fusahexin might also
CC play a role in virulence, sensitivity to osmotic stress and oxidative
CC stress (PubMed:34292732). NRPS4 is the only enzyme within the cluster
CC and its 5 catalytic modules are sufficient to produce fusahexin
CC (PubMed:34292732). The modules 1 to 4 incorporate respectively D-
CC alanine, L-leucine, D-allo-threonine, and L-proline, which is supported
CC by the presence of epimerase domains in modules 1 and 3, which
CC incorporate D-amino acids (PubMed:34292732). The terminal module is
CC responsible for incorporation of the two adjacent leucine units, where
CC the epimerase domain is only used to convert the first unit to D-
CC leucine (PubMed:34292732). The terminal condensation domain (Ct) is
CC involved in cyclization with D-alanine and thereby releasing of
CC fusahexin (PubMed:34292732). {ECO:0000269|PubMed:22862913,
CC ECO:0000269|PubMed:34292732}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:34292732}.
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 methyltransferase domains (responsible for amino acid methylation) are
CC present within the NRP synthetase. NRPS4 has the following
CC architecture: A-T-E-C-A-T-C-A-T-E-C-A-T-C-A-T-E-C-T-Ct.
CC {ECO:0000305|PubMed:22862913, ECO:0000305|PubMed:34292732}.
CC -!- DISRUPTION PHENOTYPE: Does not affect conidiation but results in
CC reduction of cell surface hydrophobicity. {ECO:0000269|PubMed:22862913,
CC ECO:0000269|PubMed:34292732}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; HG970332; CEF74592.1; -; Genomic_DNA.
DR RefSeq; XP_011318224.1; XM_011319922.1.
DR STRING; 5518.FGSG_02315P0; -.
DR GeneID; 23549697; -.
DR KEGG; fgr:FGSG_02315; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G05575; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_60_0_1; -.
DR InParanoid; I1RF49; -.
DR Proteomes; UP000070720; Chromosome 1.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
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; -; 6.
DR Gene3D; 3.30.300.30; -; 5.
DR Gene3D; 3.30.559.10; -; 9.
DR Gene3D; 3.40.50.12780; -; 5.
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; 5.
DR Pfam; PF00668; Condensation; 9.
DR Pfam; PF00550; PP-binding; 6.
DR SMART; SM00823; PKS_PP; 4.
DR SUPFAM; SSF47336; SSF47336; 6.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 5.
DR PROSITE; PS00455; AMP_BINDING; 4.
DR PROSITE; PS50075; CARRIER; 6.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 3.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..7639
FT /note="Nonribosomal peptide synthetase 4"
FT /id="PRO_0000455674"
FT DOMAIN 776..852
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22862913, ECO:0000305|PubMed:34292732"
FT DOMAIN 2313..2389
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22862913, ECO:0000305|PubMed:34292732"
FT DOMAIN 3403..3479
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22862913, ECO:0000305|PubMed:34292732"
FT DOMAIN 4944..5020
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22862913, ECO:0000305|PubMed:34292732"
FT DOMAIN 6039..6115
FT /note="Carrier 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22862913, ECO:0000305|PubMed:34292732"
FT DOMAIN 7088..7164
FT /note="Carrier 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22862913, ECO:0000305|PubMed:34292732"
FT REGION 244..636
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 865..1295
FT /note="Epimerization 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 1337..1767
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 1786..2181
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 2426..2852
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 2878..3269
FT /note="Adenylation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 3491..3928
FT /note="Epimerization 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 3961..4389
FT /note="Condensation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 4407..4810
FT /note="Adenylation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 5058..5478
FT /note="Condensation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 5498..5900
FT /note="Adenylation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 6133..6567
FT /note="Epimerization 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 6607..7032
FT /note="Condensation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT REGION 7254..7603
FT /note="Condensation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22862913,
FT ECO:0000305|PubMed:34292732"
FT MOD_RES 813
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2350
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3440
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4981
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 6076
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 7125
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 7639 AA; 843997 MW; F11CB81AFFCF07A1 CRC64;
MAPATCCCCA DSASQAMPDM EPTIFPASEI KEEIQTMISS YSSRLGHDFN QDLAKPCNMF
CLAWAILLER FTGLDNVCFG FRSEHMVTAG SERTGGVASA MQVQVTADHS VQENLDENAF
VSVMIPETKA ETLFNTTLSI CNLGNQPLCE DEARKIDVLC KLHMSVDPAT MKTLLSWDST
FMTREQAETI SNTYDKIFRE LSSKKRTTVS AIHCCSEQDE LKILSWNGSP LNNVQKCIHQ
AVSWQGAMRP DAEAVCSWDG SFSYAQLLSL SDRLAFHLKK LGVGAETFVP ICFDKSKWTI
VAMLAILKAG GIFVPLDPTQ PLLRLQNLTR KVDADTILCS PQHQEMIESI ASKVIPVDAQ
LFESLAEQRG EVDCGSWSSG AYMIFTSGTT GEPKGALIQH GALLSSALAH GPAMMMDNNT
RSLHFAASTF DVSITEILTC LILGGCVCIP SEEARLNAIE EAITQLRVNW ALLTPTFVKF
INPDNVPSLK TLVTGGEAMT QAVIRSWSHI NLINCYGPAE TSVVSHVHRG MREGKNPLNI
GHQVGIHCWV VDRYNHNRLM PVGAVGELVI ESHTLAREYY KEPEKTSEAF IVDPEWALNQ
PHHSSPRRMY KTGDLVRYNY DSSFHIAGRK DAQIKFHGQR IELGEIEYHI NVGINIKHGM
VVLPKAGFCE GRLLAIVQLS DASGHDLVPN GRPYQLIDGP LEQVAIAKVE ETKQLLTERL
PSYMVPSMWL AVEFIPRLQS GKLDRKQTGK WVEDMTEETY RKLNPVAVGD PSESLTFSNG
TESQLHNIWT HVLNLKPEQL GLSQSFLSVG GDSISAMQVM SECKKRGLGL TVSHIISCKS
ISALARHVKE IEKPMLLQET TETPFELSPI QRLYFSRSNH DQGHYNQSFL LRVSRRIDES
AMRRAIEVVI RKHSMLRARF SRDDTGRWQQ RVTDKVESSY RLRSIQLSSN EELSHALIDS
QTCLDYANGP LLAADLLDEE GQDQRLFVVA HHLVIDLVSW RIVLQELEEL LLRPELKPDM
DRPLPFQTWC QMQREHASAQ TPEQALPIHG IPDGDPTYWG MEDTPNIYGQ MVHEGFEVGS
AQTSLLLSKC HDALRTEIPD VLMAAMVYSF GQTFTDRQTP AIFAEGHGRE SWDPSIDLSN
VVGWFTTIYP VFADSDATST LIDTIKMVKD GRRKVPDNGR PYFASRWLTE SGEKAFARHW
PLEITFNYLG QYQQLEREGA LFIPVKGIAG EVSSATDGAD VGSLATCISL FEVSAVITKG
TLRFSFLFNQ NMKHQPKIRQ WIASCEQNLS LLVESLAVMS PEPTLSDFPL VSLTYDRLRL
LTQEKLPEVG IEDMGRVEDI YPCSPMQSGL LVSTTKDSAA YAAYTLHQVK SRSGGAVDVT
KLADAWKRMV DYHPMLRTVF VESVTLDESL FDQVLLKEVK VPLVMSELGT DEEAIKTLDK
ARHHDEYSQL LHVFEICKTT SGNVFCKLDI SHVIMDGTSL SILFRDLSLA YAGILGPDKG
PPYSEYIRSL QHQGLQHGIE YWKSYLMGIE PCHFPVLDDG EVVDTRESKC FRVEFDELAQ
LQRLCDDRGV TIVNAIYAAW ALVLRLYTAS EEVCFGYLTS ARDSQIEGIE DVVGPVINMV
TCRANISDST TLGDTMTVVQ NDFLNSLKHR HIPLAQVQHA LKLSDVALFN TALSYRKLPP
ALQDAPDVMF EEVRPTYDPD EYDVSINIEA GENDMMIDLT YWSDTMSDGQ ATNVASAFTT
ALSNILHHSD KPVAQLNHLG PRHHQQISQW NNVIPEAVES CVHGLFEEQA ILRPEAPAIT
SWDADFTYAE LDTTSTKLAH YLADLGVGLE QFVLVCFDKS AFAIVAMLAV LKAGGVCVPL
DPAHPDAAIR LRAEDTGASI AAVSSSMASR LSNIVDKAVV VDSNLLQNIS ENAILPQINP
HNACFVIYTS GSTGRPKGVV LEHRGIATNA KSSGPKLGYS EESRVLQFAS YTFDNSLAEI
FTTLALGGCV CVPSEHERFN DLAGAISRYR VTLADITPTV ACLINPLDVP TLKTLALGGE
AVTHKCVDIW RDFVSLQCCY GPSECSVNST YSGEIAQPGK ATNIGRAVGS VTWVVDATDH
NRLVPIGCIG ELLIDGPIVS RGYLNLPEKM AQSFVAPPAS LGDMCREGNL SRKLYKTGDL
VRYNSDGTLT YFGRKDTQVK LHGQRIELEE IEHHLEQNLP QDWTSAVELI QFEGKKSLAS
FICADLGSVR SASNEKNTVL AMDDSFRSLA KELEIALSNN LPAYMIPSVW LPVSEMPMTS
SGKLDRRSLR SMVQSLPASE MTSYKLALKS GRAPASDMEK QLASMWAHVL NVDANTIGVE
DHFFRLGGDS IAAMQLVTLA RKSNINLTVT GVFQKGSLLD MAQSALPLSR TAVATVYAFS
LLPEVVSLDA LKEEIGSCAR IQVGDVEDIY PCTPLQQGLM ALSAKEPGAY VAQLVFRLPN
GTDLDNFKMA WRLVIEAEGT LRTRLVQTTD HGILNVVVKG DVPQWSTDRS LSDLQRLRSH
LPSSNGGRLT DYAIVEDGSD VSFVWTIHHA LYDGWCLPLI LDRVKQCYEG IQSSTSEPIA
SGPTYSRFIR YLNETDSSQD VKFWESYLSD ISTQHFPRLP DPDYKPSASG LIIHKTCFDN
TRDGMKSVGL GITTATMIRS AWALTVSTYA ASDDVVFWET MTGRDVPVEG IEEMVGATLS
TVPTRIALDR SQKVSDLLSS VQAQSAVVRM HQFAGIHTIK RINTDTAFAC GAQNLLAINY
GPRTSTDSFW CDQTNEMAGT NFYSYPLMLS CHVADGELET VVHFDPDVIC ESQMHRVMDQ
FALMLTAVTS KDLVDEKLSE LDLISTRDYQ SLSEMNGQMV PSCDMCVHDV IKASGIAQPL
DKLAVCAWDQ NLTYEGLDSQ STHLSSALIE AGVRPNTFVP FCMEKSSMVV VSILAILKSG
AAFVPLDYAH PDARISGIIA DVEAEFVLSS PQYAERLTKL GAKVISVSKD TIQDSMPLQQ
HDLSVSTKSP AYCIFTSGTT GRPKGTIIDH SAFCTGALAH GKAMGMNESS RVLQFASHTF
DASIMETLST LIHGGTVCVP SEEERSQDIA GFIRRMSVNW ALLTPSVAQL IEPSTVPELK
TLVLGGEAMS RAHLSTWAPS VQLMNAYGPS ETSVVATVNS NVTLDSSPAN IGRAVGGLCW
VVDSANADRL LPIGVVGELF VEGPILSQGY LKNSQKNAES FITNPRWCSK FTSETASSER
RFYRTGDLVK ITEDGSIEFQ GRKDNQVKIN GQRLELSEIE HHLNTDAIVQ ACLAFIPTTG
PLKSRLVAVL SLHSTFVSRG PDEMQLVIDF ARSELTSVRD SLTGQLASYM IPSMWIVVNR
IPLLPSGKLD RRRVANWVEA MSPEQYQLAI GAQDESYASG LDREATETET KLRAAWAKVL
GIEVESVPFT RSFIQLGGDS ISAMQLVAIC RSSNMALSVS QIMQSKSIVK LASFVQAVED
VTQDDEQEDK AFPLSPIQKL YFERMYSDST HFNQSMVLET TRKITPQDLS NALEAIVKTH
SMLRARFSDV DGAYSQRITS DIAGSYAFES HVGMDQCRVS ELIEKTQKSL NIFQGPLLAA
ASIEMEDIDK QIVFLAVHHL VVDVVSWNII LQDLEGLLSS SASNLGKPLS FQTWNTLQLE
ESRNQTPDRV FHNLPTPAQD LAYWGMQAVP NIHGDAIAET IEIASDVSLQ LLGPCHEALN
TNVVDVLLAS LLSSFHQAFP DRLSMPTIFN EGHGREPADN KLDLSRTVGW FTTLCPVYLP
DSLPVQPDIL DIICWVRDFR RRIPGNGRPY FAHQMLSESG QKESAEWPAE LAFNYLGQRQ
KTELEGSLFK SPDGVLASVG SETDIGADVP RLALIEISAS FSRDDLSFSF SYSRQMKHQP
CIREWVKNFS ATLQTAVERM TQAKAEPQDL DTSLLPLAFR ATSKVDTRLA ELGISCCADV
EAVYPCSPVQ MGILFAQIRN PEFYSYSVTF GVNCIEPSRV VDVQRLKDAW QRVVQRHSTL
RTTFVDGLLE EGGINQVVLR NHCADISVFE RADNDELQMI TERIKPKIMS NKPPHHLSIF
SSAEGKVTCV LEMSHALSDG TSMPILFRDL AMAYEGSLDP TIVSAYRDYV SYLQCQGPND
IEYWREYLTG AEPCHLPLAS KSTLPRALGY LDQTISCAAD LQAFCTGAGV TLSNVIQLAW
ALVLQAYTGH DDVCFGYLLA DRDAPVDNID NAIGVFINML VLRVRLGSSQ SVGDALGAVQ
QDLSAAIGHK NISLTDIQRV TGLLNEPLFN TAYSFQRRSI SKSMANGSLS FDVREAQDPN
EYDLTVNVEV WDQAAELQLC YWTDKISNSQ AKTIASTFDK ILTSIATCDL SLPTNQLDIV
SDDCAQQLTR WNNTEPTLLD QCVHHVFERN VQSLPHDTPA IEAWDARFTY SEVDMLSSRL
AHHLVSLGIL PEMYVPLCFE KSAWTPIAML AVLKAGAAFV PIDPTHPPER IEFLVQNTSA
KLILCSTSLA EKFDIGVPFL AIDHETMSTL SALPVTSPSI AVQPNNAAYI IFTSGTTGLP
KGTIVEHAAF TTGGTAHAAA IKMTCSSRVL QFASYTFDAS IMEILTTFLV GGCVCVPSDE
ERMNDLAGTM AKYDVNWALL TPSVAKVLKP GSVPGLKVLV TGGEAMSTDH ITKWLGHAAL
INAYGPSEAS VIAASHTKVD ENGVILNEEP ANIGHAVGCR TWVVDPHNHN HLMPIGSIGE
LLLEGPILAR GYLKNETKTT DAFIDYPPWR ANMSLSGDRV DRMYKTGDLV SQNSDGSLNY
VSRKDTQIKL NGQRIELGEI EHHVRANLPA HVQSAVELVV PQSKTSTKTL AAFFTVDDHE
VLKETSDPLL PMSSAYMEIG QSLKTALRVA LPTHMVPTMY VPLTKMPWTS AGKLDRQKLK
TIVQSIAPQD IGGYKLVGAS NSRAPTTMMQ RKLQKIWAGI LNIHPSTISI DDSFFRLGGD
SISAMKVVSA ARMEEISLTV MDILTSPTLS EMATCCGHSE NTTVMEVEPF SLLHDVDSPP
SLLDEVADCC DVPTSQIQDL YPCSSLQEGL VAASMQQPGA YVARYIFKVP STIDMERLKM
AWQNTSNHVD ILRSRIVNAR SLKTYQAILE PHAINWEHYT SLEAIADKTI QLPERNGGVL
AKYAIIDSSD PDLRYFVWSV HHALYDAWSM PSLLNLVSQF YHEATTEQLA PPVPYANFAR
YLVDSDAQAS DEFWKATFQN ASGVSHFPTA TLSDEESTYS SLQHTIQCRR DDLGADITIP
TIVRAAWALL LGAHTGSDDV GFGETLSGRD IALEHVEDIL GPTLTTVPWR VQIDRSATVG
HFLHSLHKKS AEVIPHQHAG LQHIKRLGGS IAVASDFRNL LVIQASDEAT DHQDLLQPLE
ENGNHKNFFT YPLVVECSIE LNNLVLTIHH NETVMTSWQV ERLAHQFDAL VNQLSRLSQE
PDRKVAELQF CSEEDLQMIK GWNNGTCDAV YDTIPSLFWQ SVATYHDATS IRAWDGHLTY
GSLAQHAGHL AKRLIQEGVK AETMVPCCMD KSLWTTVAML AVVLAGGTII PMDPAHPRAR
HAEIARECKA IIALCSPEYR DRFIGVVPTV IAIDQTLFTK QLCQDHIASE DLPLVADKDA
AFVIYTSGST GKAKGVVIEH GSFVASSRAY IKHMNLSATS SVFHFTSYAF DIAMGETFGA
LTTGACLCVP SEEMRVTDLP GVMNTLGATW AFLTPSLANM QDPSMFKTLQ ALVCGGEAMT
SETVSKWSNK VKLINGYGPA ECTVFALSNS NVSEDQDHSN IGRAMDGCQT WIVDTRDHNK
LVPVGCEGEL LISGPILSRG YLNDSAKTSK SFIENPAWMH HFDDKKHQNP VRLYKTGDLV
RYRPDGNLTF IGRKDNQVKL HGQRMELGEI EACLESDPRL RNALVALPKS GVFKGRLVAV
LSFKDSDSHN PGLVSSQFSP ISESDMDVAR LHLPDLQQIL SENLPPYMMP SSWLVVEAIP
LLLSGKLDRA STQKWLTEMV AETPEFLLDQ QLGQDAGATD TTFVGQLLRK IWASVLRIPD
ESKLSGRSFI SLGGDSIMAM QVMSRCRDHS IQLTMRDIMS GKSISDLVTL IEKEGRGKQT
VNPEYEEDNS RPFALSPIQQ LFFNNSNDKD RGDRFNQSQL FSITESIDKD TFANAIHALV
QRHPMLRARF NKSSTTGQWS QQVAPDTEDS YGLHFHEVSD ASQIARQIAA SQESIGISGP
VFIVDLFKMP DGHHHVSMIA HHLVVDVVSW INIAQDLETL LSTSPSMSSK PLSFRKWNAA
QTEHATSVAK KNEDLLPFTV RPANLDYWGV SGVSNSYSQV TQQSFSLSDV DTVSLLLGDA
HQALRTEPLD LFISALLISF GQCFPDRELP TLFNEGHGRE PWDDSIDLSQ TVGWFTSLCP
IDISHHNADP TYTIDYVRKV KDVRRAIPGN GRPYFAQRYL TDSGKQSLDA HEPMEILLNF
LGRSQQSGED DSILRLSNLS MSDEDMASMS DVGPETRRLA LFELSISILD EGIQFTFMYN
KNMLHQDLIQ QWVITCKEVL GNMAMELSTA PSCPTISDFP LMSLDYAELN KLVTKSLPTA
HVRFDEVEDM YPCSPMQMGI LISQLLDPSQ YLFYAVLEVS ASSRSAIDSA KLAQACSEVV
ERHDALRTVF IESVRSGGSF DQVVLRPGKP RIATFKCREI DVMAKLNTRS LGKTNKRHGV
PILPYQITIC ETPQGKVFIK LEMNHAVTDG ASTAIVLRDI SSAYANNLHP TKAPSYKEYI
NYITKQPSDS SLMYWKSYLY GARNTEFPAM NSDHISGRSL GSIAVDFDRF SELQSLGLDA
GVTFSNMIMV AWALVLRKYT NSQDVCFGYL GSGRDADIDG VDEIVGPLIN MLVFRFQFTH
SMLLKRLFLD TQEDYANSLP HQHFSLARVS HELGQSKRGF FNTAVSIQNA GASSDADFSA
LKFESVDAFD PSEYAVTLNA NTTRGDEGIV FRYWTNILSH SQAKELAIVM SEVLSDMIDH
SEEALSHLRV SQDSSLPTNP AQDLHGWTFE HSDTSEQFKT TNSTISSYST GPGATLFSPA
TSWGSLPRDK DQVYNKLSAL WKQHLDVATT DLTYDGSFFE YGGDSIIAMA MVGDARDRDL
PLTVADIFKN PSFGTLLNCL RDKSYREGDM VSSDGNISLS GSKKEGIVVD EHTYEPLSLL
PQQNAEQFVR EHVCPVVGVS RASITDVLPT TDFQAQAIEG SLLDSRWMLN YFHLDGEGPL
DVALLQESIT NVIASYDVLR TVFVPYEATY LQVILRHVQS ELIFHDVDDV EQFTLDLESD
HLRQIPSPEK PSLRFILARH EPSERHRLFI RLSHALYDGV CFPAILNALK ASYEGEPIAT
TPSYATYIHG LFSKANPDQH TYWRSLLEGS APTNLIPREC RSMRTNPTQA LRKIVATPSL
ATVNITTATV IKAAWSVVLA KNTGTRDVVF GHLISGRNSC HVPGIEAIVG PCLNVVPVRV
QYQDSWMVLD LLQHIQHQQV DNIPHESLGF REIIRNCTNW DDDGANGFST VVQHQSMAQT
GSLDIGDNTY EVGVIASQED TADFSVVTTP QDSSNTEVCF LYREGGVERT EFAEKLFDCL
CSTIGDLSRD VKTPLVSWL
