ID KK1B_CURCL Reviewed; 13041 AA.
AC A0A348AXX4;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 1.
DT 28-JAN-2026, entry version 29.
DE RecName: Full=Nonribosomal peptide synthetase kk1B {ECO:0000303|PubMed:37746209};
DE Short=NRPS kk1B {ECO:0000303|PubMed:37746209};
DE EC=2.1.1.- {ECO:0000269|PubMed:29686660, ECO:0000269|PubMed:37746209};
DE EC=6.3.2.- {ECO:0000269|PubMed:29686660, ECO:0000269|PubMed:37746209};
DE AltName: Full=KK-1 biosynthesis cluster protein B {ECO:0000303|PubMed:37746209};
GN Name=kk1B {ECO:0000303|PubMed:37746209};
GN Synonyms=NRPS {ECO:0000303|PubMed:29686660}; ORFNames=TRAF135001;
OS Curvularia clavata.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Pleosporaceae; Curvularia.
OX NCBI_TaxID=95742;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=BAUA-2787;
RX PubMed=29686660; DOI=10.3389/fmicb.2018.00690;
RA Yoshimi A., Yamaguchi S., Fujioka T., Kawai K., Gomi K., Machida M.,
RA Abe K.;
RT "Heterologous production of a novel cyclic peptide compound, KK-1, in
RT Aspergillus oryzae.";
RL Front. Microbiol. 9:690-690(2018).
RN [2]
RP FUNCTION, INDUCTION, DOMAIN, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=37746209; DOI=10.3389/ffunb.2022.1081179;
RA Yamaguchi S., Fujioka T., Yoshimi A., Kumagai T., Umemura M., Abe K.,
RA Machida M., Kawai K.;
RT "Discovery of a gene cluster for the biosynthesis of novel cyclic peptide
RT compound, KK-1, in Curvularia clavata.";
RL Front. Fungal Biol. 3:1081179-1081179(2022).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of KK-1, a novel cyclic depsipeptide
CC with 10 residues which is a promising active compound with high
CC activity against many plant pathogens, especially Botrytis cinerea
CC (PubMed:29686660, PubMed:37746209). The nonribosomal peptide synthetase
CC (NRPS) kk1B catalyzes the elongation and cyclization of the decapeptide
CC chain composed of 1 D-lactic acid residue (D-Lac), 1 pipecolic acid
CC residue (Pip), 1 aspartic acid residue (Asp), 1 isoleucine residue
CC (Ile), 1 glycine residue (Gly), 1 tyrosine residue (Tyr) and 4 valine
CC residues (Val) (PubMed:29686660, PubMed:37746209). The Asp, Ile and 3
CC Val residues are N-methylated by the 5 methyltransferase domains from
CC the NRPS (found in modules 3, 5, 6, 7 and 9), whereas the Tyr residue
CC is O-methylated by the cluster encoded O-methyltransferase kk1A
CC (PubMed:29686660, PubMed:37746209). Cyclization with the hydroxy group
CC of the D-lactic acid as a nucleophile is presumed to occur in the final
CC module of NRPS, resulting in the formation of the depsipeptide ester
CC bond through macrocyclization by the C-terminal C domain (Probable).
CC The thioesterase kk1J is likely to be involved in the corrective
CC mechanism of peptide chain synthesis. The D-lactate dehydrogenase kk1H
CC is involved in the synthesis of D-lactic acid from pyruvic acid, which
CC is recognized by the A domain of the first kk1B module. The pyrroline-
CC 5-carboxylate reductase kk1I is involved in the synthesis of the L-
CC pipecolic acid residue of KK-1 from delta-1-pyrroline-5-carboxylate
CC (P5C), a metabolic intermediate of lysine. It is still unclear how kk1C
CC and kk1D are involved in the production of KK-1 (Probable).
CC {ECO:0000269|PubMed:29686660, ECO:0000269|PubMed:37746209,
CC ECO:0000305|PubMed:37746209}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:29686660, ECO:0000269|PubMed:37746209}.
CC -!- INDUCTION: Expression is positively regulated by the KK-1 cluster-
CC specific transcription factor kk1F. {ECO:0000269|PubMed:37746209}.
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 synthetaseTES has the following 10 modules
CC architecture: A1-T1-C1-A2-T2-C2-A3-M3-T3-C3-A4-T4-C4-A5-M5-T5-C5-A6-M6-
CC T6-C6-A7-M7-T7-C7-A8-T8-C8-A9-M9-T9-C9-A10-T10-C10.
CC {ECO:0000305|PubMed:29686660, ECO:0000305|PubMed:37746209}.
CC -!- DISRUPTION PHENOTYPE: Abolishes completely the production of KK-1.
CC {ECO:0000269|PubMed:37746209}.
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; LC371755; BBC83957.1; -; Genomic_DNA.
DR VEuPathDB; FungiDB:yc1106_06630; -.
DR GO; GO:0005737; C:cytoplasm; IEA:TreeGrafter.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0043041; P:amino acid activation for nonribosomal peptide biosynthetic process; IEA:TreeGrafter.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:TreeGrafter.
DR CDD; cd05930; A_NRPS; 9.
DR CDD; cd05918; A_NRPS_SidN3_like; 1.
DR CDD; cd02440; AdoMet_MTases; 1.
DR CDD; cd19542; CT_NRPS-like; 1.
DR CDD; cd19531; LCL_NRPS-like; 9.
DR FunFam; 3.30.300.30:FF:000084; Enniatin synthase; 5.
DR FunFam; 3.30.559.30:FF:000001; Non-ribosomal peptide synthetase; 1.
DR FunFam; 3.40.50.980:FF:000001; Non-ribosomal peptide synthetase; 1.
DR FunFam; 3.30.300.30:FF:000015; Nonribosomal peptide synthase SidD; 5.
DR FunFam; 1.10.1200.10:FF:000005; Nonribosomal peptide synthetase 1; 1.
DR Gene3D; 3.30.300.30; -; 15.
DR Gene3D; 3.40.50.980; -; 16.
DR Gene3D; 1.10.1200.10; ACP-like; 9.
DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1.
DR Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 10.
DR Gene3D; 2.30.38.10; Luciferase, Domain 3; 8.
DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 2.
DR Gene3D; 3.30.559.30; Nonribosomal peptide synthetase, condensation domain; 11.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 5.
DR InterPro; IPR010071; AA_adenyl_dom.
DR InterPro; IPR029058; AB_hydrolase_fold.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_synth/lig_dom.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensation_dom.
DR InterPro; IPR041698; Methyltransf_25.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR NCBIfam; TIGR01733; AA-adenyl-dom; 9.
DR NCBIfam; NF003417; PRK04813.1; 15.
DR NCBIfam; NF004282; PRK05691.1; 19.
DR PANTHER; PTHR45527:SF1; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR45527; NONRIBOSOMAL PEPTIDE SYNTHETASE; 1.
DR Pfam; PF00501; AMP-binding; 10.
DR Pfam; PF13193; AMP-binding_C; 3.
DR Pfam; PF00668; Condensation; 10.
DR Pfam; PF13649; Methyltransf_25; 1.
DR Pfam; PF00550; PP-binding; 10.
DR SMART; SM00823; PKS_PP; 10.
DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 10.
DR SUPFAM; SSF47336; ACP-like; 10.
DR SUPFAM; SSF52777; CoA-dependent acyltransferases; 21.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 5.
DR PROSITE; PS00455; AMP_BINDING; 10.
DR PROSITE; PS50075; CARRIER; 10.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 6.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Methyltransferase; Multifunctional enzyme;
KW Phosphopantetheine; Phosphoprotein; Repeat; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..13041
FT /note="Nonribosomal peptide synthetase kk1B"
FT /id="PRO_0000450430"
FT DOMAIN 788..864
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1865..1939
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3353..3427
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 4412..4486
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 5897..5971
FT /note="Carrier 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 7386..7460
FT /note="Carrier 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 8871..8945
FT /note="Carrier 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 9943..10017
FT /note="Carrier 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 11428..11502
FT /note="Carrier 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 12495..12569
FT /note="Carrier 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 267..663
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 882..1313
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 1341..1736
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 1957..2383
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 2418..2812
FT /note="Adenylation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 2891..3023
FT /note="Methyltransferase (M) domain 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 3445..3869
FT /note="Condensation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 3901..4300
FT /note="Adenylation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 4504..4935
FT /note="Condensation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 4963..5362
FT /note="Adenylation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 5430..5567
FT /note="Methyltransferase (M) domain 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 5989..6416
FT /note="Condensation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 6451..6845
FT /note="Adenylation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 6924..7056
FT /note="Methyltransferase (M) domain 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 7478..7901
FT /note="Condensation 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 7934..8335
FT /note="Adenylation 7"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 8404..8540
FT /note="Methyltransferase (M) domain 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 8963..9392
FT /note="Condensation 7"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 9422..9822
FT /note="Adenylation 8"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 10035..10462
FT /note="Condensation 8"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 10494..10892
FT /note="Adenylation 9"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 10959..11105
FT /note="Methyltransferase (M) domain 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 11520..11945
FT /note="Condensation 9"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 11977..12377
FT /note="Adenylation 10"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT REGION 12647..13032
FT /note="Condensation 10"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29686660"
FT MOD_RES 825
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1899
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3387
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4446
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 5931
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 7420
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 8905
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 9977
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 11462
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 12529
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 13041 AA; 1442979 MW; 7B7033EBAC8C5A63 CRC64;
MASDINTHPE GATKFWQQHF DGLNASVFPA LSSHLTVPRP NAQTAHRISY STLAKQKWDN
TSLCRAALAI LLARYSNASE ALFGVLVEQF LPSNGEQAST EESPQSILPI RIRLDLEEAG
LGLLQAINTL DASLREWKHI GLDAIRGTGE YGSAGCEFQT VLAVTTGKTP RTHRLASCTD
RALLLDCRMD DDSATLLARY DPSVIDDLQV ARFLKQLGHV IEQLRVQAVD LPLWELGIVT
QEDSAEIQKW NSQQLQFSQE CIHDVFANRV VDTPQKIAVS AWNGELTFAE LDSFSSCLAQ
HIQSLELGDA KAIPLCFEKS KWAIVGMLGV LKAGRAFTLI DPSNPPARAR QICRQTAATI
SIASPYQCDM MRALVPDCIV VDDDFFKSLA FDTDQFQPTA TPQTLAYILF TSGSTGEPKG
SMMEHHGFVS CCLEFGAALG INSNTRALQF ASYAFGACLL EILTTLMHGG TVCIPSDDER
INDAPGFIRR ANVNWAILTP SFIGAIQPTT VPNLKTLVLV GEAMPSDIRD VWASHVQLKN
AYGQSESATI CSVTEVTPAT VEAHNIGHAV GARFWITDPN NPNKLAPIGC VGELLVESPG
IARGYLIPLP ADATPFIDTL PDWYPRTQPL DNFKFYRTGD LVCYRSDGTV VYLGRRDSQI
KIRGQRVEIG EVETCLRQQL PSQLVPVVEA VSLSGMSKSM TLIAFLVGEN TILEEDVYVL
EGSAAQRISS KLRQIVPGYC IPSHYIRINH LPTTATGKCD RKALRAIGTK LLREAVEGMA
SQEEQESASL MTEGITLERI WFQSLGLKPN STRHKSNFFN LGGDSIAAIR MVNMARAAGL
LLSISDIFQN PSLAGLINVM QQSSTAQDAI PATEYSGPVE QSFAQGRLWF LDQLTTGASW
YLMPLAVRIH GPLRVQALSS ALHALEQRHE TLRTTFEQQD GMGVQIVHPS SKRELRVIDV
SGKQNGGYDQ VLKREQTTPI DLAKEPGWRA ALLRVGDDEH ILSIVIHHII YDGWSLGVLR
EELGDLYAAA LRGPDPLAHM APLPIQYRDF SVWQKQPQQV AQHQQQLVYW TKQLEDSAPA
ELLTDFPRPA ELSGRAGEVR FTIEGSVFDS LLAFRRVHQT TSFAVLLAVF RAAHYRLTGT
EDATIGTPIA NRTRAEVEKL IGFFVNTQCM RIAVADDDTF ASLVSQVWSV ATAAFEHQDV
PFERIVSALL PGARDTSRNP LAQLLFALHL EQDLDKINLE GLACETVPTP MATRFDVEFH
LFQEDDRLNG VVNFSTDLFE PQTIHSLVSV FQEILRRGLD QPQTPIAHLQ LTDGLEELRN
AGLLDIKRID YPREASVVDM FQKQVAACPN VTAVKDSTSQ LTYAQLDQES DKIAVWLRKR
NIPAETLIAL LAPRSCDSVA AFLGILKANL AYLPLDVNVP AARIEAILST VAGHKLVLLG
RDVPLLGTQL ADLELVRIGE ALRGSSSGSV AADKAIRPTA TSLAYVIFTS GSTGQPKGIM
VPHRSLVNVI KQRPAYGNVA HMTNLAFDPS LFEMCTALFN GNTLICIDTL VALDATQLPT
IFKQEAIRVA MMTPALLTRL LAQATDALHE LEALYVLGDR FPPKDAARAS ELVKTAVYNA
YGPSENSICT TLFHAATGAM CTNGVPVGRV INNSGVYVMD PKQSLVSYGV MGELVVAGEG
LAIGYTKPEL NEGRFLTLTM DGKPVRAFRT GDRVRYRPTD GQLEFFGRMD FQIKIRGHRV
ELAEVERVLN RHPAIKDAIT LLRQHGSSAQ DTELVSFIVL GEQKPVKPHR NATDHGGMEI
EQLDQKLEAN LRAMMQATLP SYMVPSRIIV LDHMPLDKNG KVDRRGLTGL TLSPAMETSS
RVVVAARNEI EAVLCEEFAH ILGVEIGVTD NFFDLGGHSL MATTLAARLA RRLNASISVK
DVFDQPIVAN LAATIKRGST PHNAIPPTKY SGPVEQSFAQ GRLWFLDQLN LGAAWYHMPL
AVRLRGPLHL EALTAALHAL EERHETLRTV FEEQDGVGMQ IVRPSSKTPL RIIDVSTKER
GYAELLKQEQ TTPFDLATEL GWRVALLRQG KDDHILSIVI HHIISDGWSL DILCEELGQF
YAAVLRGQDP LAQISPLPIQ YRDFSLWQKQ PEQVAEHHRQ LEYWTTQLEG SVPAELLTDL
PRPTIQSGKA GVIPITVNGP VYERLRAFSR AHQTTAFAVL LAAFRATHYR LSGVADATIG
TPIANRNRPE LENMIGFFVN AQCMRITVEQ DDTFETLVRQ IRFTATAAFA NQDVPFEHIV
SALMPDSRDT SRNPLVQLMF ALHAYKDLGK IELEGYVAEP VHTTLSTRFD LEFHMFQETN
HLSGYVLYAT DLFEPESIEG MVSIFKEILA RALDQPQTPL ALLPLTDGLA ELRRRGLLEI
ERPSYPRESS VVDVFCSQVA ASPNATAVKD SISQLTYAQL NEQSDKVAAW LHQCNLPTET
LVAVLAPRSC QTVVAFLGIL KANLAYLPLD VNVPAARIEA ILSEVSGHIL VLLGSHVSAP
KIELADVEFV KIDNTVEHNL PGRIGSAPSA TSLAYVIFTS GSTGKPKGVK VEHRGIVRLV
KESNVVAKMP QAARIAHLSN IAFDAATWEL YAALLNGGTL VCINYLTTLD SKALEAVFEQ
EKIQAAMLPP ALLKQYLVNI PAAIGALEVV LVAGDRFDRR DAAATQALVG AGVYNAYGPT
ENTTLSTIYN VVQGDANVNG VPIGRPVSNS GAYIMNMNQE LVPIGVIGEL VVVGDGVARG
YTDPALDVNR FVNVTIEGQT MRAYRTGDRA RYRPKDAQIE FFGRMDQQIK IRGHRIEPAE
VEHALLNNDL LQDAAVIIRK QQNDELEMVA FVEANSNKSI EQEASNQVED WGAQFESNVY
AEIEAIDASA VGNDFMGWTS MYDGSAIDKA EMQEWLDDTM QTILDGRPAG RVLEIGTGTG
MILFNLGEGL QSYVGLEPST SAAAFVNRRI QTLPAFAGKA EVHVGTATDI SQLQDLRPEV
VVINSVAQYF PSPEYLSKVL YALAQIPGVK RLFFGDMRSY AINDQFLAAR ALHNIGSKAT
KSAIRSKMVD LENSEEELLV DPTFFTNLAT ELPEVEHVEI LPKRMQATNE LSAYRYAAVV
HIRDSSERAQ TVHAIKSSAW VDFSKSQMDR KALISLLQSS VNTEAVAIGN IPYSKTIMAR
HVVQSLDEDN ADKDIAQDKP DKPTWISAVR SNAEHCPSLS ALDLVQLGEE AGFCVELSWA
QQRSHHGAID AVFHHYQPAR EGSRVLFQFP TDTYRRQSGP LTNRPLQRIQ SRRMETQVRE
KLRAVLPSYM IPSLIVLVDQ MPLNPNGKVD RKALERRAQA VLRVEKPTSE RVGARNETEA
VLCEEFTDVL GLEVGITDNF FDLGGHSLMA TKLAARISRR LDARVSVKDV FDQPVIVDLA
ASIRRGSTPH NPITPTEYSG PVEQSFAQGR LWFLDQLNLG ASLYLMPLAL RLRGPLRIDA
LTAALFALEQ RHETLRTVFK EQDGVGIQII QPSQKKKLRT IDVSAGDFSE ALHHERTAPF
DLASEPGFRV ALLQLEPSDH VLSIVMHHII YDGWSIDILC QELGQFYAAA IQGQDPLGQV
SPLPIQYRDF SVWQKQPEQV AEHERQLAYW IDQLADSAPA EFLVDLPRPP VLSGDAGLVH
LTIDGPIYDR LRAFCRVHQT TTFAVLLAAF RATHYRLTGA EDATVGTPIA NRNRPELENL
VGFFVNTQCM RISVGDDDTF EQLVRQVRST ATAAFANQDV PFERIVSTLL PGSRDTARNP
LVQLMFAVHS LKDLGKIQFE GLVGETIPTA SFTRFDVEFH LFQEVGRLSG NVLFSTDLFE
PETIQGMVSV FMEILRGALD QPQIPIAVLP LTDGLTELRN RGLLEVEQPQ YPRDSSVIDV
FRAQVVACPD AIAVKDSTSQ LTYAQLDEQS DEVAVWLHQR KLPAESLVAV LAPRSCETII
TFFGILKANL AYLPLDINVP AARIQAILSS VAGKKILLLG SDQAQPEIRL DDVEFVQINE
TIDHNMAKDN TTRSGPLATS LAYVIFTSGS TGQPKGVKVE HRGIVRLVKN SNVVAKMPEA
ACVAHLSNLA FDAATWEIYA ALLNGGSLIC IDYFTTLDSK VLEAVFEREQ IRAAMFPPAL
LKQCLLNIPT TISALDVILA AGDRFDRRDA IAAQALVGGG VYNAYGPTEN TTLSTIYNVV
DGDTNVNGIP IGLPVSNSGV YVMDPNQQLV PLGVMGELVV VGDGVARGYT DPALDVDRFI
KVEIDGQIVR AYRTGDRVRH RPKDGQIEFF GRMDQQVKIR GHRIELAEVE HVILDNSLVQ
DAAVIVHKQA DQEIEMIAFA IVRGDNDSKH PEKDILDRVK ALLPSYMVPA QMVLLNSMPL
NANGKVDRKE LAKRAGTVPR SEMAYVAPER VPPRNEIETI LCEEYAEVLG VEVGVMDNFF
DLGGHSLMAT KLAARATRRL DAKLSVKDIF DYPILANLAA AVQRGSTPHN AILATTYSGP
VEQSFAQGRL WFLDQLNVGS NWYLQPIAIR IRGSLNINAL TTALHALEQR HETLRTTFEE
EDGVGMQVVQ EYDPIELRIM DIAADYDGDY TEALKGEQTT PFDLESEPGW RVSLLRMNDN
DHILSLVLHH IISDGWSVDV LRQELKQFYA AALQGLDPLS GADPLPIQYR DFSLWQKQPE
QVAEHERQLK YWVEQLADNS PATLLADRPR PSVLSGQAGS VPLSIEGQVY EKLQAFCRAH
QTTSFSVLLA AFRAAHFRLT GVDDATIGIP IANRNRPELE HLIGFFVNRQ CMRITVGEDD
TFESLIRQVH STATAAYANQ DVPFERIVSS LLSGSRDTSR NPLVQLVFAV HSQKNLGKFE
LQDLTSEPVA GAISTRFDAE FHLFQEEERL NGVVYYATDL FDAETIQGVV SVFQEILRRG
LNHPRTPIAA LSLTDGLDNL RKMNLVHFKR TDYPRDSSMV DIFREQVATY PDVIAVKDST
LQLTYAQLDQ QSDEIATWLR NKKMAPETLV GVLAPRSCQT IVAFLGVLKA NLAYLPLDVN
APMARVETIM SSVPGSKLLL LGSDVPAQEI QLQNVELVRI EDTLGHAASA GTATTEPSPT
SLAYVIFTSG STGKPKGVMV EHRSVIRLVR KESNSMSKMS SRARVAHLTN IAFDVSAWEV
YATLLNGGTL VCVDYFTSFD AKALGLLFER EQITAAMITP TLLKQCITIV PEALRKLSVL
YTGGDRFDRR DAIATKALVK GPVYNAWGPT ETTIVSTIYE LADDDQFTNG VPIGKAVSNS
WAYVMDLNQQ LVPVGVMGEA VVIGDGLARG YTDPALDCNR FVHITIDGKR VRAYRTGDRA
RYRPKDGEIE FFGRMDRQLK IRGHRIEPAE IEHAMLGHND IVDVAIVTRH QDGAGLEMVA
FVTAHTNKSI ERNEATNQVA GWGDHFESST YAELDTLVKS DVGKDFVGWT NMYDGGAIDQ
AEMQEWLDDT IQTIVDGQPA GHVFEIGTGT GMIMFGLGKQ GLQSYVGLEP STSATTYVNR
KIKTAPTVAG KAKVYVGTAM EAAQLNGLHP EVVVINSVAQ YFPTPEYLLE VVGILTQMPG
VKRLFFGDIR SYATNRKFLA ARALHMLGSN AKKHDIRRKM AELDEFEEEL IVDPSFFTGL
VSRLPGQVKH VEILPKQMIA TNELSAYRYA AVVHLALPEE QHIAKIEKGA WVDFTATKMD
RSALVHHLQS SSNAEIVAIS NIPFSKTNFD CHLLASLDED EEHSLDGSAW IKTIHSSAEQ
CPSLSATDLV EVAKEVGFRV ELSWARQKSQ NGALDAIFHQ YQSPKEGSRV LIQFPTDDQG
RSMESLTNRP LQRVQSRRIE TQIRERLQAV LPSYMIPARI VVLNEMPVNA NGKVDRKELT
RRAKVVPRIE TAAERIQPRN EVEAVLCEEF SEVLGVEVGV TDNFFDLGGH SLMATKLAAR
TGRRLDAKVS VKDVFDHPVL ADLAAAIQRG STPHSAIVTT EYSGPVEQSY AQGRLWFLEQ
LNFKATWYLL PLAVRIRGPL NIKALTTALH ALEQRHETLR TTFIERDGVG KQAVQPFQPK
ELEIVDIAAD HQGDYLKVLR DEQTTMFNLA TQPGWRVTLH RVDQNTHNLS IVMHHIISDG
WSVDVLRHEL RQFYAAALRG QDPLAHISPL PIQYRDFSLW QKQPDQIIEH AKQLEYWTKQ
LADSSPAELP TDLPRPAVLS GKAGEVALSV KGPLYERLQA FCKTHQTTAF ATLLAAFRAT
HHRLTGAEDA TIGTPIANRN RPELENLIGF FVNAQCMRIT IDGDETFESL IRQVRATATA
AIANQDVPFE RIVSTMQSTS RDTSRNPLVQ LMFALHSQQD LGKIQLEGCE TEPIPRAVRT
RFDLEFHLYQ EQGSLGGIVY FATDLFEPES IEGMVSIFKE ILARALDQPQ TPLALLPLTD
GLAELRRRGL LEIERPSYPR ESSVVDVFCS QVAASPNATA VKDSISQLTY AQLNEQSDKV
AAWLHQCNLP TETLVAVLAP RSCQTVVAFL GILKANLAYL PLDVNVPAAR IEAILSEVSG
HILVLLGSHV SAPKIELADV EFVKIDNTVE HNLPGRIGSA PSATSLAYVI FTSGSTGKPK
GVKVEHRGIV RLVKESNVVA KMPQAARIAH LSNIAFDAAT WELYAALLNG GTLVCINYLT
TLDSKALEAV FEQEKIQAAM LPPALLKQYL VNIPAAIGAL EVVLVAGDRF DRRDAAATQA
LVGAGVYNAY GPTENTTLST IYNVVQGDAN VNGVPIGRPV SNSGAYIMNM NQELVPIGVI
GELVVVGDGV ARGYTDPALD VNRFVNVTIE GQTMRAYRTG DRARYRPKDA QIEFFGRMDQ
QIKIRGHRIE PAEVEHALLN NDLLQDAAVI IRKQQNDELE MVAFVEANSN KSIEQEASNQ
VEDWGAQFES NVYAEIEAID ASAVGNDFMG WTSMYDGSAI DKAEMQEWLD DTMQTILDGR
PAGRVLEIGT GTGMILFNLG EGLQSYVGLE PSTSAAAFVN RRIQTLPAFA GKAEVHVGTA
TDISQLQDLR PEVVVINSVA QYFPSPEYLS KVLYALAQIP GVKRLFFGDM RSYAINDQFL
AARALHNIGS KATKSAIRSK MVDLENSEEE LLVDPTFFTN LATELPEVEH VEILPKRMQA
TNELSAYRYA AVVHIRDPAR QAQTVHTIDP TAWIDFSASQ MNRTALANLL QNSADAAAIA
VSNIPYSKTI LARHIVQSLD DDLTDSDDPQ DELEGAAWMS AIRSNIKTCA SLSAFDLAQL
AQEKGFRVEL SWARQRTHHG ALDAVFHHYK SNQDGGRVLV QFPTDSRPRL SGQLTNQPLQ
RLQSRRLEAQ IRDQLSALLP SYMIPSLIVM VDEMPLNANG KVDRKALERR ARMVQKVEKP
ASERVGARNE IEAALCEVFV DLLGTEVSIT DNFFNLGGHS LMATKLAARI SRRLDARISV
KDVFDYPVLA DLAGAVQRGS TPHNPIVATP YSGPVEQSFA QGRLWFLDQL NAGSLWYIQP
IAVRVRGSLN IGALTTALNA LEKRHEPLRT TFEEHDGIGV QVVQPHQPKK LRIVDTVANY
QGDFIRALRK EQQTLFNLAT EPGWRVSLLR IGEDDNILSI VMHHIISDGW SVDILRQDLK
LFYAAALKSQ EPQVDALPIQ YRDFAFWQKQ PEQVAEHQRQ LDYWIEQLKD SKPAELITDF
PRPEVLSGTA GIVQLAVDGQ VYEGLRAFCR IHQTTSFVVL LAAFRAAHYR LTGTEDATIG
SPIANRNRPE LESLIGFFVN TQCMRIMVGE DDTFERLVQQ VRSTTTAAFA NQDVPFERIV
SSVQSTSRDA SRNPLVQLMF ALHSQQGIGL MELEGVETEP IARDVSTRFD IEFHLYQKEE
SLHGVVHFAA DLFEPETIQG LVSVFQEILR RGLETPRLPI SILPLDNNIP ELLVGMLDVD
TPEYPRDSSV VDVFRTQVAA SPDAIAVKDS TSQLTYAQLD EESNKVATWL SQRQLAPETL
VGVLAPRSCP TIVTFFGILK ASLAYLPLDV NVPSARIEAI LSAVPDHKLV FLGADVPDPE
APLVNVELVR IDDILRQSIH ASNAGLLANH PLATSLAYVM FTSGSTGKPK GVMVEHRSIV
RLVKETNLVP AVEAVSSVAH ISNVAFDAAT WEIYAALLNG GTTVCIDHIT VLDPAKLALV
FSSEKIKAAF FSTALLKQRL YEEPSTITGL DLLYAGGERM RPQDALKTRE LVRGSFCHVY
GPTENTTFST VYPMGVEERC VNGLPIGRAV SHSGAVIMDA NQRLVPLGVM GELVVTGDGL
ARGYTDPALN RDRFVEVNIH GQVLRAYRTG DQARYRPKDG QIEFSGRMDR QLKIRGHRIE
PAEVEHAILS HDDIRNAVVV TRQQEGQDLE MVAFVSTPND QTVERDEARN QVEDWGAQFE
SNVYAEIEEI DSSAVGNDFM GWTSMYDGTA IDKAEMQEWL DDTMRTLHDG RDPGHVLEVG
TGTGMILFNL GKGLQSYVGL EPSTSAAAFV NRKIETISSL AGKAKVEIGT ATDVGQLKNL
RSDLVVINSV AQYFPSPEYL VEAVTALVHI PGVKRLFFGD MRSYAMNKQF LVARALRTLG
AKANKDDVRR KMVELEEFEE ELLVDPAFFT GLANWLSEVE HVEILPKQMT STNELSSYRY
AAIVHLRLPG QEAQPVVTVN QDAWVDFGGS KMDRHALLHH LQSSPKAETV AISNIPYSKT
IYERHVLASL DDDEVEDSLD GSAWLSAVRS TAEQCASLSG VDLVQIAKEA GFRVELSWAR
QRSQKGGIDA VFHHYESVHD GARVMVKFPT DDQGRALDSL ANRPLQRLQS RRIEVQIRER
LQAVLPSYMM PVRIVVLDEM PMNANGKVDR KVLTRRAKMI SRVETTAERV GPRNEIEALL
CEEFAEVLGV EVGINDDFFD LGGHSLMATK LAARSSRRFD AKVSVKDVFD HPILADLAAS
IQRGSTPHNP ILATQYSGPV EQSFAQGRLW FLEQLNVSST WYLQPIAVRM RGPLKIEALA
AAFHALEERH ETLRTTFEEH DGIGMQVVQP HRPKELRVID VQAEHDGDYT QALHTEQTTT
FNLETEPGWR VSVFRLNEDD NILSIVMHHI ISDGWSFDIL RKEIREFYNA ALKGKDPLAQ
MSPLHIQYRD FSVWQKQLNQ ITEHKRQLDY WTKNLADNTP AELPTDLPRP AVLSGKAGVI
QLSITGPVYD RLRAFCRVHQ TTLFTVLLTV FRATHYRLTG AEDATIGTPI ANRNRPELEN
LIGFFVNTQC MRITVEEEDT FETLIHQVRT TTTAAFANQD VPFERIVSAL LPGSRDTSRN
PLSQIMFAVH SQKNISKIEL DGLESEAISR ATSTRFDLEF HLFQEEKGLG GIVLFAADLF
EPETIDSLVF VFQEILRQSL ETPKTPIAVL PLTNGIAQLR SMCVLDIEKT AYPQDSSVID
IFRQQVAARP DATAVTDSTS QLTYAQLDLH SDELASWLRQ KKMAPETLVG VLAPRSCQTI
VTFLGILKAS LAYLPLDVKV PVARIEAILS SISGQKLILL GQDVPVPEIQ LPDVDVVPIS
EILGRSVPSR ATDKSLGPLA RNLAYVLFTS GSTGKPKGVM IEHRSIVRLV KETNLISKLP
NAPRTAHLTN LVFDNSAWEI YSTLLNGGTL VCIDYATVLD SKALETVFKE QRIQTSLMPP
ALLKECLANM PTMFDDVEVL YALGDRFDKQ DAMKARSIVK TAVYNAYGPT ENTVISTIYE
IAKDDSFVNG VPIGRSISNS GAFIMDSRQQ LVPVGVLGEL VVSGDGLARG YTDPTLDVNR
FVEVTVDGQH VRVYRTGDRV RFRPKDGQIE FFSRMDQQVK IRGHRIEPAE VEHVILTNKI
IRDAAVAIRR PEGQEPEMVA FVTTHENTSI EKQSVEEFAA RIENEVRRWI KTLLPLYMVP
TQIVVLDRMP VNANGKVDRK ELAQRAQTLQ KSEAGSLPSV RVPPTNDMER ILCEEFADVL
GVEVGITDNF FDFGGHSLMA TKLAARISRR VNARVSVKSV FDHPVLVDLA STIKQDSIMH
KPIPQTAYTG PVEQSFAQGR LWFLDQLNFG ASWYLMPLAL RLQGSLHVKS LTTALFALEQ
RHETLRTTFE EQDGVGIQIV HPANKKDLRI LDVSKEQNSD YAKVLHKERT IPIDLTSEPG
WRVSLIRLGE DDHILSIVMH HIISDGWSVD VLRQELKQFY TAALKGQDPL AQIDALPIQY
RDFSLWQKLP DQVAEHQRQL EYWAEQLADN TPAELLTDLP RPDVLSGKAG AVQLTIDGPV
FDQLQAFCRA HQTTMFTVLL AVFRTTHYRL TGATDATIGT PIANRNRPEL ERLVGFFVNT
QCIRITVDVE DTFEALVRQV HSTSTTAFAN QDVPFERIVS TILPGSRDAS RNPLAQLMFA
VHSQRDISKF QLEGLDTKPI PTAASTRFDI EFHMFQQAER LSGRVLFAED LFELETIQGM
VVIFKEILRR GLETPQTPLA VLPLTDGLAH LRSQGLLEIE RPEYPRDSSM IDVFRAQVAA
CPDAIAVKDS TSQLTYSQLD DQSDKITAWL LQRKIPAESL VAVYAPRTCQ TIITFFGILK
ANLAYLPLDI NVPAARIEAI LSTISGHKLV LLGSQVSAPA VQLKDVEYVW IDEAMAETVR
TCTSPEPSAT SLAYVIFTSG STGLPKGVKV EHRGVVRLVK QSNVVAKMPQ AARVAHLSNI
AFDAATWEIY AALLNGGSLI CIDYFTTLDS KELEAVFARE KIQAAMLPPA LLKQCLVNIP
ATISALDVVL AAGDRFDRRD AAATQALVGG CVYNAYGPTE NTTLSTIYNV VKGDANVNGV
PIGRPVSNSG AYIMDPNQQL VPKGVMGELI VVGDGVARGY TDPALDVNRF IEIAIDGDQA
VRAYRTGDRA RYRPKDGQIE FFGRMDQQIK IRGHRIEPAE VEHAVLDNSM VQDAAVITRK
QDQELEMIAF VTTRSDKEID NDEASNQVED WGNQFESNIY AEIEEIDSSA IGKDFMGWTS
MYDGSAIDKD EMQEWLDDTM STLLDGRQPG HVLEIGTGTG MILFNLAERM GLKSYVGLDP
SEKATSFVKQ AIKSRPSLAG KAEVHVGTAT DVARMRDLHP EVVVINSVAQ YFPSPEYLAD
VVGALVRIPG VKRLFFGDIR SYATNNHFLA ARALHKLGEK ATRDTVRSKM AELEGYEEEL
LVDPTFFTSL TAKLHGQVEH VEILPKRMQA TNELSAYRYA AIVYIRDPKR AQTVQTVKSD
AWVDFSTSQM DRSVLVSLLQ SSDAEAIAVS NIPYSKTIVA RHIVESLSAE DSQEMLDGPA
WISAVRSSAE QCASLSAIDL VQVAKENGFR VELSCARQRS HNGAIDAVFH HYKPAQEGSR
VLLQFPTDNH IRAGSLTNRP LQRLESRRVE TKLKEHLFSV LPSYMIPSHI VMVDQMPLNA
NGKVDRKALA QRAEAVLKIE KPASERVSAR NEVEAVLCEE FTDVLGVEVG ITDNFFDLGG
HSLMATKLAA RISKHLDARV SVKDVFDYPV VADLAASIER NSIPHNPIPS TNYSGPVEQS
FAQGRLWFLD QLNMGVSELY LMPLALRLRG PLRVDAFAAA VSALEARHET LRTTFMDHDG
VGMQVILPSN SKKLRVIDAS ENDYIDILRQ ERTAPFNLTT EPGFRIALLQ LGQTDFILSI
VMHHIIYDGW SIDVLCRELG RFYSAALQGQ DPLAQVSPLP IQYRDFSIWQ KRPEQVAEHE
RQLQYWTEQL ADSSPAELLT DLPRPLVPTG KAGIVQLTIE GAVYERLRAF CRVHQTTSFA
VLLAAFRATH YRLTGAEDAT IGSPIANRNR PELESLIGFF VNTQCIRVTI REDDTFDKLV
QQVRATTTAA QVNQDVPFER IVSALMPGSR DTSRNPLVQL SFALHSQHDL GRIDLQDLTG
EALPTPVFTR LDVEFHLFQQ AEKFGGSVLF ATDLFEPETI QGLVSVFQEV LRRGLEQPQT
PIAVLPLDNA SEDLRSMGLL QMERTNYPRD SSVVDVFRDQ VAANPRAIAV KDSVLELTYA
QLDEKSDQLA AWLCQHNIPA ETIVGVLAPR SCETIIAFLG ILKANLAYLP LDDNVPAARI
ETILSAVPGH TLVLLGSHVA APSIGLADAE FVNINHTLGH SLQLNSTCAK LQPSATSLAY
VIFTSGSTGK PKGVMIEHRS IVRLVKNSNT LAKLPRAARV AHQFNLAFDA ANYEIYGTLL
NGGALICVDY STLLDIDALV AMFKREKITA SSLSPGLLKQ CVNSAPEMLK ALQVIYTGGD
RLDGRDAIEL QALVPGGVYN MYGPTENTVI STLYNLGDKH SYVNGVPIGT TVSNSGAYVM
DALQQLVPVG VMGELVVTGD GLARGYTDPE LDRNRFIKVN IDGQVVRAYR TGDRVRYRRI
DGQLEFFGRM DQQIKIRGFR IETAEVENAM LSHSAVRNAA VVVPTQDIQE KGMIGFVVIE
NNTPKNEESK EEHLLQTELA ILNRMKSILP PYMLPSRIII LDQMPSNFNG KVDRKELDRM
AQSVPRQKTT AGRIVPRNEL EASLCKEFAE VLGVEVGITD NFFDLGGHSL LATKLAARIS
RRLDTRVSVK DVFDQPVPAD LALKVSSYIS QGHAMDNGTL STTNSIPFQL LHFEDSQKFI
DRDIVPQLAH QSAKIVDVYP VTWIQKHFLV DPATGLPRTP SLFFVDFPAN ADCDKICNAS
RSLIQLFDIF RTVFVQAAGN FYQVVLEELD IPISVIETED ISTATRVLKE QDQQNPLQFG
QGFLRFAVVK TRSAVRLVLR ISHCLYDGLS FEHVVQSLHA LYNGDRIPTQ PKFVQYVQHL
TDSRKEGYDF WLSVLEESSM TVVETGRRAQ QLSSPEGAWF VEKIIKAVIP ANSDGITQAT
VFTTASTILL ARMTGSSDIT FSRLVSGRQS LPINDQHIVG PCTNIVPVRI RMTDGTNARE
LLGMVQDQYI DSLPFETLGF DDIKENCTKW PASTTNYGCC STFQNFEMQP QSQVQDERVR
LAGLTNFKDA ELLNGATATN KRVLDDVPMH EIDMIGIPEP DGLHVRVVLT ASRQIFEEEV
VDRMHEEFCD IILGLNKILQ K
//
