CCSA_ASPCL
ID CCSA_ASPCL Reviewed; 4043 AA.
AC A1CLY8;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Polyketide synthase-nonribosomal peptide synthetase {ECO:0000303|PubMed:21983160};
DE Short=PKS-NRPS {ECO:0000303|PubMed:21983160};
DE EC=2.3.1.- {ECO:0000305|PubMed:21983160, ECO:0000305|PubMed:27551732};
DE EC=6.3.2.- {ECO:0000305|PubMed:21983160, ECO:0000305|PubMed:27551732};
DE AltName: Full=Cytochalasin biosynthesis protein A {ECO:0000303|PubMed:21983160};
GN Name=ccsA {ECO:0000303|PubMed:21983160}; ORFNames=ACLA_078660;
OS Aspergillus clavatus (strain ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 /
OS NRRL 1 / QM 1276 / 107).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=344612;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 / NRRL 1;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
RN [2]
RP FUNCTION, DOMAIN, DISRUPTION PHENOTYPE, AND PATHWAY.
RC STRAIN=ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 / NRRL 1;
RX PubMed=21983160; DOI=10.1016/j.ymben.2011.09.008;
RA Qiao K., Chooi Y.H., Tang Y.;
RT "Identification and engineering of the cytochalasin gene cluster from
RT Aspergillus clavatus NRRL 1.";
RL Metab. Eng. 13:723-732(2011).
RN [3]
RP FUNCTION.
RC STRAIN=ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 / NRRL 1;
RX PubMed=24838010; DOI=10.1038/nchembio.1527;
RA Hu Y., Dietrich D., Xu W., Patel A., Thuss J.A., Wang J., Yin W.B.,
RA Qiao K., Houk K.N., Vederas J.C., Tang Y.;
RT "A carbonate-forming Baeyer-Villiger monooxygenase.";
RL Nat. Chem. Biol. 10:552-554(2014).
RN [4]
RP FUNCTION.
RX PubMed=27551732; DOI=10.1371/journal.pone.0161199;
RA Nielsen M.L., Isbrandt T., Petersen L.M., Mortensen U.H., Andersen M.R.,
RA Hoof J.B., Larsen T.O.;
RT "Linker flexibility facilitates module exchange in fungal hybrid PKS-NRPS
RT engineering.";
RL PLoS ONE 11:E0161199-E0161199(2016).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of the mycotoxins cytochalasins E and K
CC (PubMed:21983160). The hybrid PKS-NRPS synthetase ccsA and the enoyl
CC reductase ccsC are responsible for fusion of phenylalanine with an
CC octaketide backbone and subsequent release of the stable tetramic acid
CC precursor (PubMed:21983160, PubMed:27551732). The polyketide synthase
CC module (PKS) of the PKS-NRPS ccsA is responsible for the synthesis of
CC the octaketide backbone (PubMed:21983160). The downstream nonribosomal
CC peptide synthetase (NRPS) amidates the carboxyl end of the octaketide
CC with a phenylalanine (PubMed:21983160). A reductase-like domain (R) at
CC the C-terminus catalyzes the reductive release of the polyketide-amino
CC acid intermediate (PubMed:21983160). Because ccsA lacks a designated
CC enoylreductase (ER) domain, the required activity is provided the enoyl
CC reductase ccsC (PubMed:21983160, PubMed:27551732). Upon formation of
CC the 11-membered carbocycle-fused perhydroisoindolone intermediate, a
CC number of oxidative steps are required to afford the final cytochalasin
CC E and K, including two hydroxylations at C17 and C18, one alcohol
CC oxidation at C17, one epoxidation at C6 and C7 and two Baeyer-Villiger
CC oxidations (PubMed:21983160). The oxidative modification at C17, C18
CC and the C6-C7 epoxidation are likely to be catalyzed by the two
CC cytochrome P450 oxygenases ccsD and ccsG (PubMed:21983160). CcsD may be
CC responsible for the epoxidation of the C6-C7 double bond
CC (PubMed:21983160). CcsG may be responsible for the successive oxidative
CC modifications at C17 and C18 (PubMed:21983160). The double Baeyer-
CC Villiger oxidations of ketocytochalasin to precytochalasin and
CC cytochalasin Z(16) are among the final steps leading to cytochalasin E
CC and K and are catalyzed by ccsB (PubMed:21983160, PubMed:24838010). The
CC first oxygen insertion step follows that of the classic BVMO mechanism,
CC generating the ester precytochalasin (PubMed:24838010). Release of
CC precytochalasin into an aqueous environment can generate the shunt
CC product iso-precytochalasin through spontaneous isomerization
CC (PubMed:24838010). Alternatively, precytochalasin can undergo further
CC oxidation by ccsB to yield the in-line carbonate-containing
CC cytochalasin Z(16) (PubMed:24838010). Cytochalasin Z(16) is a precursor
CC to cytochalasin E and cytochalasin K, whereas iso-precytochalasin is a
CC precursor to cytochalasin Z(17) and rosellichalasin (PubMed:21983160,
CC PubMed:24838010). The hydrolyase ccsE may catalyze hydrolysis of
CC epoxide bond in cytochalasin E to afford cytochalasin K
CC (PubMed:21983160). The function of ccsF has not been assigned but it
CC may play a role in post-PKS-NRPS biosynthetic step, resistance or
CC transport of cytochalasins and related PKS-NRPS products
CC (PubMed:21983160). {ECO:0000269|PubMed:21983160,
CC ECO:0000269|PubMed:24838010, ECO:0000269|PubMed:27551732}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:21983160}.
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 (By similarity). CcsA contains
CC also a polyketide synthase module (PKS) consisting of several catalytic
CC domains including a ketoacyl synthase domain (KS), an acyl transferase
CC domain (AT), a dehydratase domain (DH), a methyltransferase domain
CC (MT), and a ketoreductase domain (KR). Instead of a thioesterase domain
CC (TE), CcsA finishes with a reductase-like domain (R) for peptide
CC release. CcsA has the following architecture: KS-AT-DH-KR-PCP-C-A-T-R
CC (PubMed:21983160). {ECO:0000250|UniProtKB:Q4WAZ9,
CC ECO:0000305|PubMed:21983160}.
CC -!- DISRUPTION PHENOTYPE: Loss of cytochalasin E and cytochalasin K
CC production. {ECO:0000269|PubMed:21983160}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; DS027057; EAW09117.1; -; Genomic_DNA.
DR RefSeq; XP_001270543.1; XM_001270542.1.
DR SMR; A1CLY8; -.
DR STRING; 5057.CADACLAP00007112; -.
DR PRIDE; A1CLY8; -.
DR EnsemblFungi; EAW09117; EAW09117; ACLA_078660.
DR GeneID; 4702673; -.
DR KEGG; act:ACLA_078660; -.
DR VEuPathDB; FungiDB:ACLA_078660; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_37_5_1; -.
DR OMA; NEQMRFG; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000006701; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
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:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
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; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
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 InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Isomerase; Ligase; Methyltransferase;
KW Multifunctional enzyme; NADP; Oxidoreductase; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Repeat; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..4043
FT /note="Polyketide synthase-nonribosomal peptide synthetase"
FT /id="PRO_0000431479"
FT DOMAIN 2394..2475
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3617..3697
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 11..449
FT /note="Ketoacyl synthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT REGION 557..877
FT /note="Acyl transferase"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT REGION 945..1243
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT REGION 1400..1585
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT REGION 2115..2288
FT /note="Ketoreductase (KR)domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT REGION 2395..2472
FT /note="Peptidyl carrier protein"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT REGION 2476..2575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2587..2630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2640..3069
FT /note="Condensation"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT REGION 3102..3502
FT /note="Adenylation"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT REGION 3622..3694
FT /note="Thiolation"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT REGION 3735..3954
FT /note="Reductase-like"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21983160"
FT COMPBIAS 2492..2534
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2559..2573
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2594..2608
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2615..2630
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 181
FT /note="For ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2435
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3657
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 4043 AA; 445741 MW; E914ABF892E54658 CRC64;
MGSFQNSSEP IAIIGTGCRF PGGCDSPSKL WELLRAPRDL LKEIPESRFS VDSFYHPDNA
HHGTSNVRHS YFLEEDLRQF DVQFFGIKPI EANAVDPQQR LLLETVYEGL ESAGLSIQRL
QGSDTAVYVG VMSADFTDLV GRDTETFPTY FATGTARSIL SNRLSYFFDW HGPSLTIDTA
CSSSLIAMHH AVQTLRSGDS SLAIVAGSNL ILGPEQYIAE SKLQMLSPTG RSRMWDAAAD
GYARGEGVAA IVLKRLSQAI ADGDHIECVI RETGVNQDGK TPGITMPSAT AQAALIRSTY
AKAGLDLSNR SDRPQYFEAH GTGTPAGDPI EARAIQTAFF GPDLNFTADS RKDTLFVGSI
KTVVGHTEGT AGLAAVIKAS LALQSGTIPP NRLLEQLNPA IKPFYNSLKI LAAAEDWPQL
SRGGVRRVSV NSFGFGGANS HAILESYEPS LHSHKGTRDI SFSPFTFSAA SETALVASLR
AYRDLLSTRS DVRLTDLAWT LNSRRSTLAS RVAIAASDKD DLVLKLDDRA ENYDGSDTFM
DAGHRKPNAN ELRILGVFTG QGAQWARMGA ELIEQCPGAS KVVDALEQSL RSLPPQDRPT
WSLREQLLAP PSSSMVSTAS ISQPLCTAIQ IMLVDMLREA GIQFSAVVGH SSGEIGAAYA
AGCLSAKDAI RVAYYRGVHL KSALQKGSML AVGTTFEDAQ DLCNLPTFED RLCVAASNSP
SSVTISGDSD AIEEIKVVFD EEKKFTRLLK VDRAYHSHHM QDCVEPYVRS LRQCSVTFRP
PNRNQCVWIS SVFVQDIHQL SEDGSDRYWG SNLARPVMFA EALQLLLSLE GSFDLAVEVG
PHPALKGPAS QTIQDALGYS IPYTGVLSRG NSDVEAFAAA LGSIWTAFGD GAVDFSRLQK
FTSGSAAQPQ LLKGLPTYQW DHNRVFWHES RVSKAFRTRK DVPNELLGRQ VLDGAPNQLR
WRNILRPREI AWLEGHQVQG QMVFPCAGYV SACAEASMRL AVGQNVESIE LEEFVVGQAI
VFNDSNSEVE TLATLTEVVH RQQTISANFA FYSCPTGGES LELVRNASCR LRITVGDSAV
DLLQPQAEAD FALLEVESDR FYNALGQLGF GYTGPFRSLT ALKRKLGIAR GLIENAPPSF
NHSQPLLIHP ATLDAAIQSI MLAYCYPGDS MLRAIHLPTG IEKLTLNPVN CLKFAGQSVQ
VPFDSSASTG SGRSLQGDVS IYSLDGSRAV QLEGLQTQPL SSPTEASDLN IFTELVWGVD
RPDCEEILRT TVVEDFDAEL LFSLERVAYF YLRSLGEAVP ERERNGLEWH HKRLFAYVDH
VLSRVARGVN RFARPEWAAD SKNDILKILQ KYPDNIDLRL MRAVGENLPA VVRGQLTMLE
PMIQDNMLND FYVIAHGMPR YTKYLAAMAS QISHRYPHMN VLEIGAGTGG ATKSFLKELG
EGFSTYTFTD ISSGFFEKAS QVFASYSAKM NFKVLDIEKD IESQGFAPES FDLIIASLVL
HATRDLAQTV RNVRRLLKPG GYLLLLEITE NEQMRFGLIF GGLPGWWLGY EDGRPFSPCV
DIEEWSRVLE QNGFSGIETA IPHHDTLPAP LSVIVSQAVN EKVQFLHNPL DSIRGSTVIP
RLTIIGGGGR RSAQLIDAVS SLVQPQCGQL RVVDSLQKIC SEVLPVGGSV LSLTDFDEPV
FKSMDADKLR GFQEIFKQSK NVLWVTQGSR SGDPYARMVV GFGRTIVLEM LHLRLQFLDV
SPSSSPDASA IAEAMLRLEV SGSWEDEGAE DGAVLHSVEP ELSISDGRCW VPRFKPNKEQ
NERYNSVRRS IETEQSFSDT CVELVYRDNS LSLLEVTHSS SEPLAEPSTK YLELDVNYSV
SKAVEVVPGC YLFLILGRDT DTGDRFIALS PKQSSRVRIP RALVLPQHTS HGTINENSLD
AFFHEIVARS ILRDVPYGSA AIALQPNSLL ADALREAAQD KGVTLHLWST QASDLESEWT
YIHRKASKTE VQNAIPRNVT CFFDMGGDES IATKILACLP DHTQAKKEAS ITAHEAHLIP
TVLPDIRSLL MDIGRAMRTR GKSSSPDLRI VDLTDIVKGQ ADSETSIINW LESSSRVPVA
VEPIEARVQF RSDRTYWLVG LTGGLGLSLC EWMAQQGARY IVLSSRSPKV DGRWLAKMNR
MGVTVEVVAN DISNRDSVQR VYNKIRTELP PISGVAQGAM VLHDTMFLDL DMERMNKVLR
PKVDGSTYLE EIFHDTELEF FVFFSSMAAV TGNPGQSAYA AANMFMASLA NQRRQRGLNA
SAVHIGAIFG NGYVTRELTL VQQEFLRKVG NLWLSEHDFR RLFAEAVYAG RHHRGRSPEL
STGLKILESD ESESITWFNN PVFQHCIKQS GRVDLISETS TSAAPVKVRL AEASSSADIY
DIISDAFVTK LKTSLQVEGD RPIVDLTADT LGIDSLVAVD IRSWFIKELQ VEIPVLKILS
GATVGEMVTQ AQELLPKELT PNLDPNAEAK PSKPKNTVQP KQQTKKTIQL QNVAKAPQPA
LSQQVSSGVQ NMIKTNPPKE AEAKQPRPEV KQAAPKDSQY PTALETPSKL QDPSRNIVVA
KDLAAEEKHL TDQEPVPSNM SSSSWSEIDE SEGKVETSSS SSSTSASQII TKTKPVEVKK
SVPMAFGQSR FWFLRHYLED PSSFNITVSI QLDGPLKIDH FARAVQVVGQ RHEALRTRFV
TDEAQGTTKQ EVLALSNLTL EERTISTDEE AEGVYQELKG YAFDLEKGEN IRIILLKRSN
RSFTLIIAYH HINMDGVSLE VLLRDLQMAY DSKFLSPRIL QYADFSEQQR RDYQSGKWAE
DLAFWKKEFQ TMPGPLPLLS MARTSTRSPL TAYKTHSAEF HIDPATLDTI QSTCQRMKVT
PFHFHLAVFY TMLIRLVDVE NLCIGISSAN RSQQDTLQSV GLYLNLLPLN FTPQLDQTFT
NVLHIVREKS VQAFAHSKVP FDVIVNELGA ARSATHSPLF QVLVNYRAGV SERRSFCNCD
SKVLTFEQGQ TPYDLSLDVI DNPGGDCHVI MAGQSVLYGA EHVAVLRGVY QNLLVAFSRN
PALRLNVPPL YDTDEVKHAI KLGHGPAYNY QWPATIPERI DEIVERYPTH VALIDGDGRK
MSYTEMARRV NTLAVVLLRQ DIGQGSKVGV FMEPGSSWIC SLLAILRLDA IYIPLDSRMG
LDRLSTIVRD CKPDLLLVDN TTLSNVALLG LSCPTLNVDV VSPGSDQQHV PNTAQPSSTA
VIMYTSGSTG VPKGIVMQHH TFRNNIETST EKWDFREGRE TTLQQSSYSF DMSLSQTFLT
LSNGGTLRIV PKKLRGDPKA IASLITAEGI TFTETTPSEY ISWLRYGDVD DLRKSKWRIA
VSGGETITTN LTGLLRQLEK SDLRLIDCYG PTEITFCSHG REVQYDGEGD ILSPAFRTWP
NYSVYIVDSH MKPVPIGIPG EILIGGAGVV AGYVHSELDA RGFARNNFMN TMFLENAWTR
LHRTGDFGRL DQEGNLILGG RIAGDTQVKL RGIRIDLQEI ESAILSSGDG KIVDAAVTVR
ESADSGSEYL MAFVTTLDAG DLSLERIRQE LPLPQHMRPA NIITLDQLPM TASNKVDRLA
LKSLPLPPGS HVADTGTDES PSMAKMRDVW ATVIPQEVLA HFELGPASNF FQVGGDSMLL
VRLQTEINKV FGTSISLFQL FDASSLTGMV SLIDHSESTS QRSEVDWETE TTISPSLLQV
PATKRFFAHP AVVVLTGATG FLGRAIVNRL LKDCSVQKIH CVAVRRDPSS LPDDFKSPKV
VLHRGDLTLP QLGLTDRAAT EIFAEADAVI HNGADVSFMK TYQSLKQANL EATKELVRLS
APHRLSFHYI SSASVTRLAG QESFDQSSVS AFPPSAEDGY VASKWASERY LEKVSDQCGL
PIWIHRPSSI VGEGAPDTDM MASLLGYSRT LRAIPQTDGW TGWLDFVSAD RVAMQIADEV
YEDYSWPGTV KYLYEAGDRE IPLSDLRGVL ERETGESFES IPLEEWVLRA EGQGLHPLLG
EYLRRVSGIP LVLPRLVQQG SFF
