NRPS5_GIBZE
ID NRPS5_GIBZE Reviewed; 11197 AA.
AC I1SAJ7; A0A098DZ30;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Nonribosomal peptide synthetase 5 {ECO:0000303|PubMed:17043871};
DE Short=NRPS 5 {ECO:0000303|PubMed:30804501};
DE EC=6.3.2.- {ECO:0000305|PubMed:30804501};
DE AltName: Full=C64 cluster protein NRPS5 {ECO:0000303|PubMed:25333987};
DE AltName: Full=Fg3_54 cluster protein NRPS5 {ECO:0000303|PubMed:30804501};
DE AltName: Full=Fusaoctaxin A biosynthesis cluster protein NRPS5 {ECO:0000303|PubMed:30804501};
GN Name=NRPS5 {ECO:0000303|PubMed:30804501};
GN Synonyms=NPS5 {ECO:0000303|PubMed:17043871}; ORFNames=FGRAMPH1_01T20955;
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 IDENTIFICATION.
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RG EnsemblFungi;
RL Submitted (JAN-2017) to UniProtKB.
RN [5]
RP IDENTIFICATION, AND DOMAIN.
RX PubMed=17043871; DOI=10.1007/s00294-006-0103-0;
RA Tobiasen C., Aahman J., Ravnholt K.S., Bjerrum M.J., Grell M.N., Giese H.;
RT "Nonribosomal peptide synthetase (NPS) genes in Fusarium graminearum, F.
RT culmorum and F. pseudograminearium and identification of NPS2 as the
RT producer of ferricrocin.";
RL Curr. Genet. 51:43-58(2007).
RN [6]
RP INDUCTION.
RX PubMed=23266949; DOI=10.1105/tpc.112.105957;
RA Zhang X.W., Jia L.J., Zhang Y., Jiang G., Li X., Zhang D., Tang W.H.;
RT "In planta stage-specific fungal gene profiling elucidates the molecular
RT strategies of Fusarium graminearum growing inside wheat coleoptiles.";
RL Plant Cell 24:5159-5176(2012).
RN [7]
RP IDENTIFICATION, AND INDUCTION.
RX PubMed=25333987; DOI=10.1371/journal.pone.0110311;
RA Sieber C.M., Lee W., Wong P., Muensterkoetter M., Mewes H.W., Schmeitzl C.,
RA Varga E., Berthiller F., Adam G., Gueldener U.;
RT "The Fusarium graminearum genome reveals more secondary metabolite gene
RT clusters and hints of horizontal gene transfer.";
RL PLoS ONE 9:e110311-e110311(2014).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=30804501; DOI=10.1038/s41467-019-08726-9;
RA Jia L.J., Tang H.Y., Wang W.Q., Yuan T.L., Wei W.Q., Pang B., Gong X.M.,
RA Wang S.F., Li Y.J., Zhang D., Liu W., Tang W.H.;
RT "A linear nonribosomal octapeptide from Fusarium graminearum facilitates
RT cell-to-cell invasion of wheat.";
RL Nat. Commun. 10:922-922(2019).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=31100892; DOI=10.3390/toxins11050277;
RA Westphal K.R., Nielsen K.A.H., Wollenberg R.D., Moellehoej M.B.,
RA Bachleitner S., Studt L., Lysoee E., Giese H., Wimmer R., Soerensen J.L.,
RA Sondergaard T.E.;
RT "Fusaoctaxin A, an example of a two-step mechanism for non-ribosomal
RT peptide assembly and maturation in fungi.";
RL Toxins 11:0-0(2019).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the Fg3_54/C64 gene
CC cluster that mediates the biosynthesis of the octapeptide fusaoctaxin
CC A, a virulence factor that is required for cell-to-cell invasiveness of
CC plant host (PubMed:30804501). The 2 nonribosomal peptide synthetases
CC NRPS9 and NRPS5 form an assembly line which likely utilizes GABA as a
CC starter unit (loaded on the unique module M1 of NRPS9) and sequentially
CC incorporates seven extender units composed of the residues L-Ala, L-
CC allo-Ile, L-Ser, L-Val, L-Ser, L-Leu and L-Leu, respectively
CC (PubMed:30804501, PubMed:31100892). During the process, each of the
CC residues that are tethered on modules M3-M7 of NRPS5 containing an E
CC domain can undergo an epimerization reaction to produce a D-
CC configuration before the transpeptidation reaction occurs
CC (PubMed:30804501, PubMed:31100892). The elongation of the peptidyl
CC chain might be terminated by module M8-mediated L-Leu incorporation,
CC followed by R domain-catalyzed 4 electron reduction to release the
CC resulting octapeptide from the assembly line as an alcohol
CC (PubMed:30804501, PubMed:31100892). Fusaoctaxin A is cleaved by the
CC cluster specific ABC transporter FGM5 to the pentapeptide fusapentaxin
CC A and the tripeptide fusatrixin A (PubMed:31100892). The other enzymes
CC from the cluster, FGM1, FGM2, FGM3 and FGM9 seem not to be involved in
CC the biosynthesis of fusaoctaxin A and their functions have still to be
CC determined (Probable). {ECO:0000269|PubMed:30804501,
CC ECO:0000269|PubMed:31100892, ECO:0000305|PubMed:30804501}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30804501, ECO:0000269|PubMed:31100892}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor FGM4 and is induced during infection of
CC coleoptiles of wheat seedlings (PubMed:23266949, PubMed:25333987). The
CC fusaoctaxin A gene cluster is silenced by H3K27 trimethylation by the
CC histone methyltransferase KMT6 (PubMed:31100892).
CC {ECO:0000269|PubMed:23266949, ECO:0000269|PubMed:25333987,
CC ECO:0000269|PubMed:31100892}.
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. NRPS5 has the following 7 module
CC architecture: A-C-A-T-C-A-T-E-C-A-T-E-C-A-T-E-C-A-T-E-C-A-T-E-C-A-T-TE.
CC {ECO:0000305|PubMed:17043871, ECO:0000305|PubMed:30804501}.
CC -!- DISRUPTION PHENOTYPE: Produces significantly smaller lesions on
CC susceptible wheat cultivars. {ECO:0000269|PubMed:30804501}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; HG970334; CEF87111.1; -; Genomic_DNA.
DR RefSeq; XP_011325382.1; XM_011327080.1.
DR STRING; 5518.FGSG_13878P0; -.
DR GeneID; 23560681; -.
DR KEGG; fgr:FGSG_13878; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G20955; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_60_6_1; -.
DR InParanoid; I1SAJ7; -.
DR PHI-base; PHI:9042; -.
DR Proteomes; UP000070720; Chromosome 3.
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 GO; GO:0009058; P:biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 6.
DR Gene3D; 3.30.300.30; -; 7.
DR Gene3D; 3.30.559.10; -; 13.
DR Gene3D; 3.40.50.12780; -; 9.
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; IPR013120; Far_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 8.
DR Pfam; PF00668; Condensation; 13.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 7.
DR SMART; SM00823; PKS_PP; 7.
DR SUPFAM; SSF47336; SSF47336; 6.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 6.
DR PROSITE; PS00455; AMP_BINDING; 5.
DR PROSITE; PS50075; CARRIER; 7.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Repeat; Virulence.
FT CHAIN 1..11197
FT /note="Nonribosomal peptide synthetase 5"
FT /id="PRO_0000449944"
FT DOMAIN 1446..1522
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:30804501"
FT DOMAIN 2945..3021
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:30804501"
FT DOMAIN 4508..4584
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:30804501"
FT DOMAIN 6068..6141
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:30804501"
FT DOMAIN 7636..7712
FT /note="Carrier 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:30804501"
FT DOMAIN 9173..9248
FT /note="Carrier 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:30804501"
FT DOMAIN 10663..10749
FT /note="Carrier 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:30804501"
FT REGION 19..413
FT /note="Adenylation (A) domain 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 426..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 690..897
FT /note="Condensation (C) domain 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 918..1310
FT /note="Adenylation (A) domain 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 1952..2380
FT /note="Condensation (C) domain 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 2406..2805
FT /note="Adenylation (A) domain 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 3041..3481
FT /note="Epimerase (E) domain 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 3515..3957
FT /note="Condensation (C) domain 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 3976..4371
FT /note="Adenylation (A) domain 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 4603..5022
FT /note="Epimerase (E) domain 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 5069..5501
FT /note="Condensation (C) domain 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 5521..5918
FT /note="Adenylation (A) domain 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 6162..6512
FT /note="Epimerase (E) domain 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 6636..7076
FT /note="Condensation (C) domain 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 7097..7491
FT /note="Adenylation (A) domain 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 7733..8162
FT /note="Epimerase (E) domain 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 8205..8638
FT /note="Condensation (C) domain 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 8660..8832
FT /note="Adenylation (A) domain 7"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 9565..9683
FT /note="Epimerase (E) domain 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 9721..10116
FT /note="Condensation (C) domain 7"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 10136..10529
FT /note="Adenylation (A) domain 8"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT REGION 10806..11104
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30804501"
FT MOD_RES 1483
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2982
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4545
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 6102
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 7673
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 9209
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 10708
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 11197 AA; 1225540 MW; 2A473FE7E5354F07 CRC64;
MLAGRPPPPV SSLVHDMIAQ RARKQPDAEA SISWDTTMTY ADLDELSDTV ASHLVSIGLQ
VGSTVVTCLD KSGWVPAIYL SILKAGGAFA PVSPGLSADQ LTSAMRRLSP SIVISSTPNL
SKFVGLAEHV LDISEILKTP KNTNTQLLSS LTVAVQDPAC VLFTSKGEGE ETLLVLDHVA
VCTSIVTNSN VHDFSPATRT LQFAPYDSRA SISDVLFTLA AGGCVCTVSE EEQTGRIADA
CTRMNPSLVC LTPSSAAVLN QDDLPGIDTI ILAGEHLDKD SVGKWATVAN LINAYAPTAA
LGYACCTAPL ITISSPRNIG WPRGCAAWVM DPQDPTRLAP PGAVGQLLVE SPFLGQSYES
GDGGSASALV PRPECLSRPM FSLKPAGDER CFLTEHLVQF DIGDGTLQVV GHKNSKGQLL
QFDSHHASSS ASSVGETPGV TGPISTPMGD SVSETSLDTT AIDVNLETTD TRTTLLGLSP
EKLSRLEALL QPLGQVQQCY PCCSVQEGIL VSQVKSPGTY NILVVWELVN ASTVSLDRLR
TAWERVVKRH APLRSTFVES LRDGSVFDQV VLTSPSVDVV ELPWIEDLTE DDDMLKLTSV
TWDMGRPHHR LGLSKAADGR LRCQLLISHA VIDGLSVQAL GHDLERSLND LLPNSGSMDL
QSRYFQQLQQ IPSEGGPRVY TKRRLLPNIK QLRQFCQEQG TTLFSLTQTA WALVLRAYTL
SDDVCFAYMA TDRHLLGDDA DRAVGFFINL MLCRVGLDGS TPIADVLNKL RQDFVEGFPY
QHHPLAEIAH EQGVPASQLF NTTITFMSDD ETVEPHCDGV QLHRVADQDV AEYDVVLRVF
DSYQDNVAVE FSYWSSSLSS AQAENVFGAF LAAITSIPQS TTVDDVQLMD ESMKQQIQQW
NSQLPMHVDT CTHDLILDAA QDYPDAPAVE SHDGSLSYGE FDVMTGKLAA HLKSLDVGHG
IPVVFRMEKS LWAIVAMVGI MRAGCHFVPL DPAWPVERTQ FIIDNVGASI LLTTESTPAL
PVQHINHTVV LSPELLNKLP TENSLLPHVK PSDPAYILYT SGSTGQPKGV VVEHQTLSSS
STAHGKAMLM DRQTRAFQFS SFTFDVSLGE IMTTLVHGGC VCIPSSDDRL SNISGAISKL
RANQLFMTTT TLGTFSPEDC PTVKTVVCGG ELLSQAIKDV WAPHVNLLHG YGPTEACIYA
VSGHANDPTL PPSVIGHAMD GNRVWVCRPD DPRILSPIGA LGELIIEGPI VAREYFNDSD
RTNTSFLDRI PESWGTPSPY RLYRTGDLVR WNMDGSLTFF GRHDGQLKVR GQRCEAGDIE
NHLTTIEPDI AHCAALVPKQ GACASMLVAV LSFKTTHPVL STTTGEVQLL DTQQVSGIIA
KLQESLAQQV PGYMVPQVWL PVVSLPSTTA CKTDRRRVSR WVDQLDKATL DNVLNLATTH
SATPLADRSP VHMMLATAWG EVLGTPVEFI PDDRSFFSLG GDSILAILVV NRCRAQGIEL
SVSDILRGRT INDMANNIAI SEQHSTSDSS TQGHVTAAHS LALGSGYDLE SPVLSQSRTA
QLQLASSIDQ HTLEDAVRQL IHLHPALRTT YVKEDDAWFA RESTDVSKVL LFVSHDGTEA
KSSALLDATE GPLLAVDYFP GHNRVAVSAL HITLDLASWN LVLRDLDCIL SGSPVIPHAR
PAMDTRASPS HTDEPSVVAN LDYWELDPEE TYLPHESKYE LRIDADASQL LFESCSRSML
TVVDVVVAAA AESFSRSFTD RTVPVIHAAD TPRTHVGYGD SVYPVQLTND LVSSGTAVVA
ATAKNARLAS SKEISSYMAE SYTPKVLAAR LPEILVRCLD NARFQGNLLQ QQGDDLDTAT
LIPSCISITV SPNDDKSLGV VVAHSWDLGQ QKKVRKWVRV LQTALLDTIR AVARANFVSP
ADFPLVKVSD DKAWEQLRST INEAVGPSGP TVEDVYPCSP VQQGMLISQA KSTSSYTVDV
VWKIHAPSGS PAVSIAKLEN AWAKVVQRHS ALRTIFVDGS AANEAFLATV LRNPSARVIH
QTVVGEDAVE SLLAFDPELP VASHEPPHVL TIADAQDKIL VHLRINHAVV DGISLDVLQR
DLHRAYVDEV GSEWSVSDHS FRDYVAYVKA QDSDKSLDFW KNRLNTVSAC RFPQLQVPDV
AIANEKRIFK TQIDDIAPLL KLCQTNGVSI SNLAQLAWAL VLRGYTNNHH VCFGYMTSGR
DAPVSGIESA AGVFINLVIS DLALDDAMTV KEALESSRAG LADSMDHQYC PLSKVQKALD
MGGEPFFNTV LSCYREDDVT PSKTGVAVDL VHLDDTSEFA IAAKIAYTRS TMELSLTYRT
EVICPEAADV IGDVWLRTLQ SLPSLSDTKI SDISLMDPLS SKLVKRWNEH VPGPVDACLH
DIITDVARIE PDKMALYSSA GTLTYAELDE FSTRLGHHLV SMGVGPEVIV PLLFEKSIWA
VVAMLGVLKA GGAFVALDPA HPAERLALII SDTGSPVMVM SANQATTPLV TGDLSNLEVA
MFTVTHESIL ELPALSDKPC PTVTPDNAAY VIFTSGSTGR PKGVVIEHRA VSTGTKEHGS
QMNYTSTSRV LQFASYAFDA TIGEVFTTLV YNGTVCIATE TERIEDLTGF INRANVDWAF
LTPAVARMMT PSDVPTLETL ICGGEPIGDL TPRIWSEIKF IQAYGPTETC VFASISDRQH
REVRPAIIGH MMGSAAWVVS PSNSDLLVPV GSVGEMLIEG PILGRGYRND PDKTDASFIR
DPEWSVHYPR HSNGRRLYKT GDLVRYNLDG SMDFVQRKDT QIKIRGQRVE AGEIESHVTS
AHKDVQHVYV TFVKNGRLSS RLVAIISLKG FGSTESSSSG SLQVLKGDDY DRAKELLRTV
TEYLSSKLPR HMVPAVWAVV EGSSVPLTTS GKIDRRLMTN WLEKADEDLV RQILALGQEE
SVSDDSLTST EVTIRSVWAL VLNLDPQKIN SEHRFFSLGG DSITAMQVVS HCRSQGIALT
VKDIFKHQTI ASLAAFVDYD SAGKIGAPAT GNEFDLSDPV EESFALSPIQ KMFFDIYPDG
VNHFNQSFLV QIASGNKVAS PTLHAALNQL VSRHSMLRAR YTRSQGQWVQ RVTDDVNGSL
QYQEHKNTSL GQISNLIDLA QQSLDIQHGP LVSAKLIQLP SRQILALVAH HLVVDMVSWR
VLLEELEAIL TGKPLAPASV QPVPFQAWVR VQSTLAEELS AHNVLPYPVP EPRQDYWGID
LAKSNGWAST REISFELNEA MTKAILGPCN EPLQTDPQDL FLAAAFRSFA QAFPDRPLPA
IFTEGHGRDA DVDVDLSRTV GWFTCIVPVA LAQDVPEDLL ETTMRIKDSR RSVPGHGVPY
FSYRYMSGDG VTGNEFRQHD QMEILFNYHG QYQQLERDGA LLQTIPEGEF AQRDVDNSAR
RLAVFDISVA VVSGRARVSM LMPQSLAPTL AQQVEVWSDS FQDKLADVVY KTSTMKSEFT
LNDTPLIKDM SYPNLAEMKT LCLEHTGKWG PGSIEEIFPC SPMQEGILLS QMRTPDLYDV
RFAFEVSSHD SSPQVSRLHE AWEQVVKRQP MLRTVFLPNL RGSGSFDQAI LRKTLATVHH
IELEELAEPS SHLVKRVLET MEKAPASSFE YGKVPHELSI YTVGDRMFIL LRLSHALVDG
ASLPYIIKDL QQAYMHKLPA APGLGYRELV SFIQKQPMDE ALEYWSGYLD GAGPCRLPLL
LDDAVIPSPG KLEARDIPVP VPDAKALRSL CAKYGVTMAS IFHAAWALIL RAYIGDDEVH
FGYLASGRDA PIQGITSLIG PLINMLISRV NFDRSKTVAQ LLQDICEDFA SSMSNQYASL
AQVQHSLGLG SEPLFTTVVS FQRHDPTSAG ADGGSDGIKL TGIDSRDPTE YDVSLNVVDS
DQELSFTFTY WTSKISSAHA THMIRALLSA LTSFAENVDQ PIVNVNLVSP ETRCELDSWN
AIGMQELHTE CAHTLFEQQV EKIPDQQAIC AWDGNFTYRE LNEASNAFAH HLYSLGEATP
KPDEFVITCF DKSAWATVSQ MAILKAGAAF AAVDPTYPIV RVKTIVNDLR ASVLFTETKY
KDRFQGIFSK VIVVDQEMLD SIGGPQLDAP STPVNGNNLS YSIFTSGSTG QPKGILIEHQ
SLSTVAKHFA KPYQIDQNTR TLQFAAYTFD LSVGETFMTL LNGGCLCITS ERRRLEDLTG
AINDFQVNWA FLTPTMADIL DPAQVPSMKS LALAGEAATS ENIRKWHDKV HFVIAYGPAE
TTICCNATDG VKATSDPANF GPARGAGIWV ADMDDPSILL PVGAVGELLV EGPIVGRGYV
DPIKTAEVFI DPPTWLTTQY PRVYRSGDIV RYNPDGTCSF VRRRDNQVKV RGQRIELNEV
EVHVSQADAD LQHTVVLLPK TGACQGRLTT VLSRHQQQEK VEAQRVLCPV TSEEDRSRNS
TLRNKLSSTL PGYMIPKIWI TVEQLPLTTN GKMDRRKIQD WVHALTEQEL AAIVSSTETT
VTGTQDTRKL TPMEQQLVKA WSQVLNLPAS SLPLDQSFTS LGGDSISAMQ IVSKARECGV
TVSVDKVLRS ESLSELANHA RFKALAPNSN GIQSLVVEKT EPFPLLPIQR MFFEMNPSGN
NHFNQTFTVR LSKTLSAERI ESAITTVVKH HPMLRARFLK DHNSDWTQQI VPDAESSLGF
RQQSFASLSD AVPVLDELQT SLDIHNGPLV ASCLINLPDA QVLSLAAHHL VVDLVSWRVI
LSDLEILLSS ESKSLPSLAP AAVTMPAWTD ALLSRAKDYN VESVLPFTVP SANFGFWDMD
NGRENVMADT VVIQSRLDAS STAALLGRAN IAFRTDPDDL MLAALVFSFL RVFPERSVPT
IYAEGHGRNA WDDSIDLSRT VGWFTTMYPL VASATTRDLV ETVRQVKDIR HSIRDKGFPY
FASRYLTAQG RDAFKEHTNM EVLFNYLGQY QQLQQSDTVL RELQEPLEIQ DAAPSTPRMA
LIDILAAVEG SEMVLSIGYN GRMGHRDRLQ LWLNEYTAAL RSLSTELPTM SPSFTPGDFP
LLGIDDAGLK SLAATCKAKV GSLDPTMVES IYPCSPLQQG ILVSQAQDAK SYIVYAAWKI
RPARGTSFNV NQLKDAWRRL VRYHPVLRTV FCENGTSDGG HAQVLLRADT AAAEPTIKEI
QCQRSDVAEF LRSSASSLPT DKPPHILSIC TTDDDTYVSL QVSHALIDGT SMNLVMDDLV
RSYNGNLQGS GPSYNDYISH ICSEPIARSL SYWTETLADT QPCLFPVLST EGTKRVLNKI
TLDVPSSTTD AMRQLGRAHA ISVSNIFQLA WSLVLRAFTG SDSVCFGYLT SGRDVPVDRI
EAMVGPLISM LVSSTQFGSS DDEAQSALDL LKSINRSYID SLPHQHCSLG SIQNALGVSN
TGLFNTVMSL QKINEEAETP EEFGFDLLDS HDPSEYNMTL NILDFNNIVE LHFTYWTDKL
SDSYASTVVD ATLRAVEAIV KDPSRKMPVV DLVGDSERQG LVSRINQDHP TLQTTVHALI
EAQVKAIPDN CAVTSWEGDL SYTELDHHAT RLAVHLRSLG VGPEVTVPLC FKKSIWTVVA
ILAVMKAGGV FVPLDPAHPA DRIKGIVEQL PSRIVALTSP QCVLTVAHLV DNTISVDASS
IAQLENVSSA ESLSPGATPS NAVYIIFTSG STGQPKGVVL EHSAAASGTT AHGHDMSYSR
DSRVLQFSSY SFDASILEIL TTLVYGGCIC VLSEEERIND LVGGINRLRV NWAFLTPAVA
MMVEPSQVPT LRLLALGGAP LWLAVLQKWT AVGTIRVVNG YGPTECCALS THNYYSRSYM
RPEVIGKAMG CNTWVVDPRD PNILMPIGAV GELLIEGPIV ARGYLNDLVK TQDAFLNGVS
WLPSGRLYRT GDIVSYATEG NGDKISYIRR KDTQVKVRGQ RIELGEISYQ IGASHGSIVA
HLVVLGSRGK FSGQIVAIFA LDGFPTHQQG NDEPLQLLDS PQDLAKVRAI ISEVSEFISD
KLPSSMQPSA MVPVNRMPIN TSGKIEARRV SAWVDGLDDA TYARIMRIAD EPDDEPDNEP
EANVIQKSEA EDIIRAVVAE VVNVPLEQIP LRRSFFAIGG DSISAMAVVS RCRSRGITFT
VSDIFKHKTI TALAQFVSQS TQQITKKDGD GIDRSDKVNV DFSLSPIQQM FFDMYPDGVN
HFNQSFLVQL PSTEALTSTV VHEAIRQLVD RHSMLRARFS DEDGDWVQRV TPSGDAKSLK
YQVHNGVNVD QVVKLIDVAQ TSLDIRTGPV MAASLLNLTD KRRILVLVAH HLVIDMVSWR
VLLEELEVIL SGNGHSLQNM PTSLPFQAWV RTQPRRVSKW SPSRVLPYDI PKPRMDYWLK
RGEDNTCGDT RELGFTLDAD ATKALLGSCN EAFQTDPQDL FLAAAFQSFA DAFPDRGPPA
IFVEGHGRGD GASEGLDLSR TVGWFTSIVP VALPDGVVAT NVVDTLMRIK DVRRSVPGQG
VPYFSYRYLS AAGVRKFRNH DKMEILFNYF GQYQQLERDD ALLRPVVGDE FPQYDADASV
ERLAIFDVAG AVTSGRASVT ITMPGTLAKA RVDGVSLWLD RLKHHLTSLV QVTSDMSTAF
TLHDLPLIKN MSYDELSDMR EVCLEHTGLW GPGAIEEIFP CSPIQQGILL SQAHRPDLYD
VRVALEVSSR NGSLSAQSLG DAWRHVVQRQ PMLRTVFLPN MRGNGSFDQA VLRDPVPSIR
HVDLGDATDD EMALQTVKQS IAETKGDIFS YGKLPHEFTT YTIGNKTFVF IRLSHALVDG
FSLPIVLNDL REAFAHRLST TPGLSYRELV SFINEQPADQ AIGHWVDFLK GSTPCRLPPL
LDDASVPSSP ELLAIEVEVP CSNALRALCA EHGVTMAIVF QLAWALVLRA YTGEDDVMFG
YLTSGRDAPI EGVSTLVGPL INMLTCRAIF NDRSKTVLQL LSQLQDDFIN GISNQHVSLA
EIQHHLGIGS EGLFTSIISF QRHDAAAGAA NDDDGLLKMT PIDGRDPTEY DLSVNVLDEA
DKDIQIHFTH WTSKASPSHA KHMMQALSAA LVAISTKPNQ PLVKVDLVGA ETRREMDSWN
ATGIQFVSDE CIHNIIERNS QAMPDRQAIC GWDRTFTYGE LDQAANAFAH HIHSLVDLKP
DTFVATCFGK SAWTIVAQLA ILKSGGAFVA IDPTHPADRV ETILSELGSP PILLTESKHQ
DRFKTLFPNI VTVNEDTLSS LSVPNGPPST RVRHSNTAYA IFTSGSTGRP KGIVIEHGSL
STAALTHAGP YQITSDTRAL QFAAYTFDVS IGETFYPLSQ GGCVCVPSDA ARLEDLAGAI
NGLSADWAFL TPTVADLLDP SLVPGLKTLV LGGEAPTSVN IRRWHDKVFL ISGYGPAETT
IWCNATGRLN GSSDPANLGP PMGARVWVTD ADDPSVLLPV GAVGELLIEG PLVSRGYTDP
EKTAAAFISP PGWMTTAYPG KLIYRSGDIG RSRPDGTFSF VRRRDNQVKV RGQRVELNEV
EVHISQAETS IRHAVVLYPK SGACQGRLTA VLSHHSLGGE ELEQKQTVPG SGGIIAVQSD
EAISASDLIQ DRLLSTLPPY MIPKIWITVE HLPSTTNGKM DRRQILTWVE SLTDDNLASI
VQRKSNMTGS VESPTKPKTK MEEHFLQIWS NALNLPIDAI PHNQPFTSLG GDSITAMQVL
ARARERGITT TVHDILRSRS IADLAGRSRF KNIQLNGSED SKALTVITDQ PFALLPIQRL
FFRTQTSVNH HFNQSFIVCL SRPFTADQVR MAIRAIVEHH PMLRARFLAD GNEWKQKISP
DIAGSFKFQQ HHCSSLPDSV ETLDDLQASL NISQGPLLVS CLLELSDGQA LFLAAHHLVV
DLVSWRVILA DLEKLLAATS GTTSLPSLEQ EGISMPAWTE ALIQKSTEYD INSVLPFTVP
AADFSFWDMD PTKETNIMAD TASLQVRVDG VSTAALLGPA NAAFGTDPDD LMIAALIFSF
RSIFHERSSI PAVYTESHGR NAWDDGIDLS RTVGWLTTIY PVAVSDIDNA ERDLLRVVRQ
VKDIRRSIPG KGLPYFAYRY LTEEGRAAFE HHDEMEILFN YLGQYQQLQK TDTIIQQIGE
TTLSTQDASD STNRLALMDV VAAVEGSELV LSLGYNTKMQ HKHRFQAWLD SFKYMLETLA
SQLPVIPATF TPSDLPLLSL GEDGLSTLAA ACHAKVGSWG PDVVEASYPC SPLQQGILLS
QAKDESAYVV SGIWKVSPAK GGSPVNLDQL QNAWRRLVQY HQILRTVFCE SGRNDGIYAQ
VVLRENTTES QPTIEVRKCD GPDPLAFLHS STPALPSDKP PHALLICDAG TDVYLSFNIS
HALMDGTSLG LMMDDLLRGY HGTLEGVGPS YEPYIAHVYN KPASESLSYW SDTLANARPC
HFPVLVDAEG DDTVRSLNKI MRPVPGVEAM RQLGRTHGVS IANFFQVAWA LVLRAFTGSD
DICFGYLTSG RDVPVDRIEE IVGPLISMLV SSADFSMSDG APSAIELLQT MNSAYVDSLP
HQHCSLADIQ RVLRIGNKGL FNTALSLQRV TTGDETQDQI EINVVEGDDP SEYNITVNVV
DYGETIDLHF TYWSDKISDS HASDVVEALI RALDAIVQDP NRTLPAVDML GDSGRKRIME
WNGDGQAPAA LNSTVHALIE AHVKESPNRC AVTSSWEGEL SYAELDNHAT RLSVYLRSLG
VGPEVTVPLI FTKSIWMVVS MLAVMKAGGV FVPLDPAHPP ERIAMIVEQL PNRAVALASP
DRTGLISGLV DNVVALDADE AACIAKDADG DNKLPSDEAT PDNAVYIIFT SGSTGQPKGV
VLDHRATATE IVTTLVYGGC VCVLSEDERI NDLAAAINRL QATWMLLTPA VASTLDPSEV
PCIRYIALGG ESSSHATNKK WSKGCKVLHA YGPTECCVMC AYDDRTGLLT RPEVIGGSVG
CNNWVVDPRD PSVLMPIGAV GELLVQGPIM ARGYLNNPDK TQESFLDTGL PSVSGLSRAY
KTGDLVSYCS EGKGNKLTFV RRKDTQVKVR GQRIELGEIS HQISASNDKV ATQMVTLGSR
GTLNGKIVAV LTLRGLQTTE DGGDTEPLQI LDNPKDIQIA RDIVAEVQNY IADKLPGYMH
PSVMIVVNRM PINSSGKLET RRVAQWVDEV TDEMYERIIK NLADNEPEAG SESAQTAVVQ
IISEAVAEVI NLPGKVSLRR SFISMGGDSI TAMQVMALCR RRGVSLPVQD ILKSNNIIAM
AAKAQQIGGS SVDSAKDEDE FAPFPLSPIQ KLHLTQFRDG ENHYNQSMLL KLRRPISETV
LHEALLQLVR RHPMLRARFD NDSTRGQWTQ RVTNDIQGSL SYAVTEFNTL EEAMGTMIEA
ERGLDITAGP LVAARVVRVH DSMSIFLVAH HLVIDLVSWR IVLQDLEQLI AGTSLPGTQM
SWSYQRWAHS LMKYAETNAS TALALPFTPT EPDLDFWGVK KTSNDFNNLV QGDFTLDPSL
TSALLDSADK NLKAEVLDVL LAMAAHTFSS VFSDRAAPTF HTETHGRDHP QDTTASVHET
IGWFTAIAPL VLDTPSDEYI DSVIRVKDMR RAIPGLGIPY FTAKTLQGSQ TLPVEILFNY
LGRFQQLERD DGLFESLPKS MGPVDVNLSA ARLSVIDISA VVEKDALTVS WNYSAQIQHQ
DKLSKWFALY EQALHEVVSA LQKTSLQLTK SDVPLLPISH QQLKPLNKAL AAVSRNGVEA
VEDVYPTSPM QRGILLSQSK DASQYDVHAV WEITPANRHD SVDVSRLQRA WYRVIQRHSM
LRTVFIDSVV DNSPFDQVVL NKFRPSIKLL TYDDDEEDHD SMMEELWESA NGSFAQNAPP
HRLALCSDTQ GKVYAHFQVS HALIDAGSLR TIIKDWSLAY ASPNLTMTPD QSEIRHLHTD
VDSGTRLKAL AKELNISMAS IFQLAWALVL RSYTNLQDIC FGYVSSGRDV ELDGIVDAVG
PFINILVSRI VFGKGDTAAA MLKQLFSTYL DSLPHQHASL ADITHALKMP GGKLFNTAFS
FQKISQSNGG GKAQDLPLSF STIGGADPTE FDVTITVIEN DSSIEFSIQY STSFLSEPQA
NNLSQSLIQA LDAIEATPSE AIETLDLVPA KHMEQLKTWG DRLPPTVDRH VHDLFDDMVR
STPTAPAIHA WDGEFTYAEL DRESSRLAGL LLKQGVKPDT FVALCFEKSA WVAVAYLAIL
KAGAAFMLLD PEAPIERIQY MMEQTKTSMV LCSPTYKDMV DDWDATAIVI SKEVMGTLPD
FAGPFPNIST SSAAYIIFTS GTTGKPKGAV IEHGAYSSSA IAQKKALYIG PGSRFLQFAS
FMFDATMIEM VTPLLSGGCV CIPRRQDIIS DLPRVVREMN INMAILTSSF IRTMSPEEVP
TIKRLIQGGE PLSQKDIDIW ADKVILGNAY GPSECSVMAS CLSDVLRTSE PSNIGYPAAC
AHWVTEPANM HRLVPIGAIG ELLLQGPTLS RGYINNPDKT AEAFVTGLNW ATQVGRDPDT
RFYATGDLVR LNSDGSVTFV GRKDTQIKIH GQRMELGEIQ HHLTTIDEIR HSVVLSPSEG
PLQKRLVAVL ELANLSSTAA SSEEIKLIEP SLRSKATESI QRIRDIITQR LPSYMIPSTW
IVVQSMPTMI SGKLNLPAVQ FWVQNINDET YQELHAAEAV SELDSSDYVA MQVSRKLSSL
LVDAPGSTGK LEDFVGKDIV PMQCGLDSIT AITFSTWLRK TFGVTISLAT LLSLDTSIQT
LAVTIKADMA KVGSSGPSNV ESVTESTSTT KAAIDLHSEF QHYDQALSQL PVSEIPNTGV
AKIPSNFLVT GSTGFLGSQI VRQLILRPNI NKVFCLVRAE DDIQAQERMM EVARKGQWWQ
PELSERIEAW SGDLAKPHLG LDDTRWASVV GGSIDAIIHN GAMVHWHLGY RDLKDANVGS
TFDLLSALSK APSPPRFAYV TGGYFPDEER TDNEVLDLLQ GGDGYSQTKF LSEALVRSHG
QRLCRHSATF PMPVVIQPGL VIGDADHGVS NLDDFLWRVV ASALRIGAYN VDEFNDPNAW
LLVAGSDQIA TSTIDACMTT VSASATTTIP PSIRFVDGVP VKELWNLLID EFDFSLRPMS
GPEWLQALEN DMDSQGPSHP LFPVFEFLQL KQGAVGTLKP TNGDSICPQV ETLYRLRQSV
DYLNNIGFFA SSDSVSPFAS KAAFRRTGLR PAKTAHF
