PIKA1_STRVZ
ID PIKA1_STRVZ Reviewed; 4613 AA.
AC Q9ZGI5;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Narbonolide/10-deoxymethynolide synthase PikA1, modules 1 and 2 {ECO:0000305};
DE EC=2.3.1.239 {ECO:0000269|PubMed:10421766, ECO:0000305|PubMed:19437523};
DE EC=2.3.1.240 {ECO:0000269|PubMed:10421766, ECO:0000305|PubMed:19437523};
DE AltName: Full=Narbonolide/10-deoxymethynolide synthase PikAI {ECO:0000305};
DE AltName: Full=Pikromycin polyketide synthase component PikAI {ECO:0000303|PubMed:19437523};
DE Short=Pikromycin PKS component PikAI {ECO:0000303|PubMed:19437523};
DE AltName: Full=Type I modular polyketide synthase PikAI {ECO:0000303|PubMed:19437523};
DE Short=PKS {ECO:0000303|PubMed:19437523};
GN Name=pikAI {ECO:0000303|PubMed:9770448};
OS Streptomyces venezuelae.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=54571;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 15439 / DSM 41110 / IMRU3627 / M-2140;
RX PubMed=9770448; DOI=10.1073/pnas.95.21.12111;
RA Xue Y., Zhao L., Liu H.W., Sherman D.H.;
RT "A gene cluster for macrolide antibiotic biosynthesis in Streptomyces
RT venezuelae: architecture of metabolic diversity.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:12111-12116(1998).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10421766; DOI=10.1016/s1074-5521(99)80087-8;
RA Tang L., Fu H., Betlach M.C., McDaniel R.;
RT "Elucidating the mechanism of chain termination switching in the
RT picromycin/methymycin polyketide synthase.";
RL Chem. Biol. 6:553-558(1999).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18512859; DOI=10.1002/cbic.200700635;
RA Gupta S., Lakshmanan V., Kim B.S., Fecik R., Reynolds K.A.;
RT "Generation of novel pikromycin antibiotic products through
RT mutasynthesis.";
RL ChemBioChem 9:1609-1616(2008).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-1281, SUBUNIT, AND ACTIVE
RP SITE.
RX PubMed=19437523; DOI=10.1002/cbic.200900098;
RA Yan J., Gupta S., Sherman D.H., Reynolds K.A.;
RT "Functional dissection of a multimodular polypeptide of the pikromycin
RT polyketide synthase into monomodules by using a matched pair of
RT heterologous docking domains.";
RL ChemBioChem 10:1537-1543(2009).
RN [5]
RP FUNCTION, PATHWAY, COFACTOR, AND SUBUNIT.
RX PubMed=19027305; DOI=10.1016/j.bmc.2008.10.082;
RA Kittendorf J.D., Sherman D.H.;
RT "The methymycin/pikromycin pathway: a model for metabolic diversity in
RT natural product biosynthesis.";
RL Bioorg. Med. Chem. 17:2137-2146(2009).
CC -!- FUNCTION: Involved in the biosynthesis of 12- and 14-membered ring
CC macrolactone antibiotics such as methymycin and neomethymycin, and
CC pikromycin and narbomycin, respectively. Component of the pikromycin
CC PKS which catalyzes the biosynthesis of both precursors 10-
CC deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-
CC membered ring macrolactone) (PubMed:18512859, PubMed:19437523). Chain
CC elongation through PikAI, PikAII and PikAIII followed by thioesterase
CC catalyzed termination results in the production of 10-deoxymethynolide,
CC while continued elongation through PikAIV, followed by thioesterase
CC (TE) catalyzed cyclization results in the biosynthesis of the
CC narbonolide. {ECO:0000269|PubMed:10421766, ECO:0000269|PubMed:18512859,
CC ECO:0000269|PubMed:19437523, ECO:0000305|PubMed:19027305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5 (S)-methylmalonyl-CoA + 11 H(+) + malonyl-CoA + 5 NADPH =
CC 10-deoxymethynolide + 6 CO2 + 6 CoA + 2 H2O + 5 NADP(+);
CC Xref=Rhea:RHEA:43056, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:29461, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57327, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=2.3.1.239;
CC Evidence={ECO:0000269|PubMed:10421766, ECO:0000305|PubMed:19437523};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6 (S)-methylmalonyl-CoA + 12 H(+) + malonyl-CoA + 5 NADPH = 7
CC CO2 + 7 CoA + 2 H2O + 5 NADP(+) + narbonolide; Xref=Rhea:RHEA:42844,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:29650, ChEBI:CHEBI:57287, ChEBI:CHEBI:57327,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=2.3.1.240; Evidence={ECO:0000269|PubMed:10421766,
CC ECO:0000305|PubMed:19437523};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305|PubMed:19027305};
CC Note=Binds 3 phosphopantetheines covalently. {ECO:0000305};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:19027305,
CC ECO:0000305|PubMed:9770448}.
CC -!- SUBUNIT: Homodimer (By similarity). Pikromycin PKS consists of a
CC combination of multimodular (PikAI and PikAII) and monomodular (PikAIII
CC and PikAIV) polypeptides each coding for a functional synthase subunit
CC which participates in 1 (monomodular) or 2 (multimodular) of the six
CC FAS-like elongation steps required for formation of the polyketide.
CC Module 1, 2, 3, 4, 5, and 6 participating in biosynthesis steps 1, 2,
CC 3, 4, 5, and 6, respectively. {ECO:0000250|UniProtKB:Q03131,
CC ECO:0000250|UniProtKB:Q9ZGI4, ECO:0000305|PubMed:19027305,
CC ECO:0000305|PubMed:19437523}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are unable to produce
CC methymycin, neomethymycin, narbomycin and pikromycin.
CC {ECO:0000269|PubMed:18512859, ECO:0000269|PubMed:9770448}.
CC -!- MISCELLANEOUS: Type I modular polyketide synthases (PKSs) catalyze the
CC step-wise condensation of simple carboxylic acid derivatives.
CC Organizationally, type I PKSs are arranged into modules, wherein each
CC module is comprised of a set of catalytic activities that is
CC responsible for a single elongation of the polyketide chain and the
CC appropriate reductive processing of the beta-keto functionality. A
CC minimal elongation module contains an acyl transferase (AT) domain, an
CC acyl-carrier protein (ACP) domain, and a ketosynthase (KS) domain. The
CC AT domain is responsible for loading the methylmalonyl-CoA extender
CC unit onto the phosphopantetheinylated ACP domain. Subsequently, the KS
CC domain decarboxylates and then condenses the ACP-bound extender unit
CC with the growing polyketide chain obtained from the preceding module to
CC yield an ACP-bound beta-ketoacyl intermediate. In addition to the three
CC core domains, each elongation module may contain up to three additional
CC domains: a ketoreductase (KR), dehydratase (DH), and an enoyl reductase
CC (ER) that are responsible for the reductive processing of the beta-keto
CC functionality prior to the next extension step. The presence of a KR
CC domain alone gives rise to a beta-hydroxyl functionality, the presence
CC of both a KR and a DH domain generates an alkene, while the combination
CC of KR, DH, and ER results in complete reduction to the alkane. Finally,
CC a thioesterase (TE) domain, typically found at the terminus of the last
CC elongation module, catalyzes the termination of polyketide
CC biosynthesis. The activity of this domain results in cleavage of the
CC acyl chain from the adjacent ACP and formation of the macrocyclic ring.
CC {ECO:0000305|PubMed:19027305}.
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DR EMBL; AF079138; AAC69329.1; -; Genomic_DNA.
DR PIR; T17409; T17409.
DR SMR; Q9ZGI5; -.
DR KEGG; ag:AAC69329; -.
DR BioCyc; MetaCyc:MON-18411; -.
DR BRENDA; 2.3.1.239; 6106.
DR BRENDA; 2.3.1.240; 6106.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IDA:UniProtKB.
DR GO; GO:0031177; F:phosphopantetheine binding; TAS:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0033068; P:macrolide biosynthetic process; IDA:UniProtKB.
DR Gene3D; 1.10.1200.10; -; 3.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 3.
DR Gene3D; 3.40.47.10; -; 3.
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; 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; 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; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 3.
DR Pfam; PF16197; KAsynt_C_assoc; 3.
DR Pfam; PF00109; ketoacyl-synt; 3.
DR Pfam; PF02801; Ketoacyl-synt_C; 3.
DR Pfam; PF08659; KR; 2.
DR Pfam; PF00550; PP-binding; 3.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 3.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 3.
DR SMART; SM00823; PKS_PP; 3.
DR SUPFAM; SSF47336; SSF47336; 3.
DR SUPFAM; SSF51735; SSF51735; 4.
DR SUPFAM; SSF52151; SSF52151; 3.
DR SUPFAM; SSF53901; SSF53901; 3.
DR SUPFAM; SSF55048; SSF55048; 3.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 2.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 1: Evidence at protein level;
KW Acyltransferase; Antibiotic biosynthesis; Multifunctional enzyme; NADP;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..4613
FT /note="Narbonolide/10-deoxymethynolide synthase PikA1,
FT modules 1 and 2"
FT /id="PRO_0000436357"
FT DOMAIN 1007..1085
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2495..2570
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 4404..4482
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 31..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..1082
FT /note="Loading domain"
FT /evidence="ECO:0000305"
FT REGION 91..518
FT /note="Beta-ketoacyl synthase 1"
FT /evidence="ECO:0000305"
FT REGION 634..917
FT /note="Acyltransferase 1"
FT /evidence="ECO:0000305"
FT REGION 1111..2567
FT /note="Module 1"
FT /evidence="ECO:0000305"
FT REGION 1111..1539
FT /note="Beta-ketoacyl synthase 2"
FT /evidence="ECO:0000305"
FT REGION 1650..1956
FT /note="Acyltransferase 2"
FT /evidence="ECO:0000305"
FT REGION 2208..2385
FT /note="Beta-ketoacyl reductase 1"
FT /evidence="ECO:0000305"
FT REGION 2606..4479
FT /note="Module 2"
FT /evidence="ECO:0000305"
FT REGION 2606..3032
FT /note="Beta-ketoacyl synthase 3"
FT /evidence="ECO:0000305"
FT REGION 3057..3079
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3180..3470
FT /note="Acyltransferase 3"
FT /evidence="ECO:0000305"
FT REGION 3471..3494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3579..3877
FT /note="Dehydratase"
FT /evidence="ECO:0000305"
FT REGION 4100..4281
FT /note="Beta-ketoacyl reductase 2"
FT /evidence="ECO:0000305"
FT REGION 4363..4383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4483..4508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4551..4613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4364..4378
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4491..4508
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 724
FT /note="Acyl-ester intermediate; for acyltransferase 1
FT activity"
FT /evidence="ECO:0000305"
FT ACT_SITE 1281
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022,
FT ECO:0000305|PubMed:19437523"
FT ACT_SITE 1740
FT /note="Acyl-ester intermediate; for acyltransferase 2
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q03133,
FT ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2355
FT /note="For beta-ketoacyl reductase 1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03131,
FT ECO:0000250|UniProtKB:Q03132"
FT ACT_SITE 2776
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 3 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 3273
FT /note="Acyl-ester intermediate; for acyltransferase 3
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q03133,
FT ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 4250
FT /note="For beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03131,
FT ECO:0000250|UniProtKB:Q03132"
FT BINDING 2216..2219
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /ligand_note="for beta-ketoacyl reductase 1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 2239..2242
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /ligand_note="for beta-ketoacyl reductase 1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 2268..2269
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /ligand_note="for beta-ketoacyl reductase 1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 2318
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /ligand_note="for beta-ketoacyl reductase 1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 2340..2341
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /ligand_note="for beta-ketoacyl reductase 1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 4108..4111
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /ligand_note="for beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000305"
FT BINDING 4132..4135
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /ligand_note="for beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000305"
FT BINDING 4161..4162
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /ligand_note="for beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000305"
FT BINDING 4211
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /ligand_note="for beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000305"
FT BINDING 4235..4236
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /ligand_note="for beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000305"
FT MOD_RES 1045
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2530
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4442
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 1281
FT /note="C->A: Does not produce any detectable levels of
FT methymycin or pikromycin."
FT /evidence="ECO:0000269|PubMed:19437523"
SQ SEQUENCE 4613 AA; 477293 MW; A3BAF8D37CEC9383 CRC64;
MSSAGITRTG ARTPVTGRGA AAWDTGEVRV RRGLPPAGPD HAEHSFSRAP TGDVRAELIR
GEMSTVSKSE SEEFVSVSND AGSAHGTAEP VAVVGISCRV PGARDPREFW ELLAAGGQAV
TDVPADRWNA GDFYDPDRSA PGRSNSRWGG FIEDVDRFDA AFFGISPREA AEMDPQQRLA
LELGWEALER AGIDPSSLTG TRTGVFAGAI WDDYATLKHR QGGAAITPHT VTGLHRGIIA
NRLSYTLGLR GPSMVVDSGQ SSSLVAVHLA CESLRRGESE LALAGGVSLN LVPDSIIGAS
KFGGLSPDGR AYTFDARANG YVRGEGGGFV VLKRLSRAVA DGDPVLAVIR GSAVNNGGAA
QGMTTPDAQA QEAVLREAHE RAGTAPADVR YVELHGTGTP VGDPIEAAAL GAALGTGRPA
GQPLLVGSVK TNIGHLEGAA GIAGLIKAVL AVRGRALPAS LNYETPNPAI PFEELNLRVN
TEYLPWEPEH DGQRMVVGVS SFGMGGTNAH VVLEEAPGGC RGASVVESTV GGSAVGGGVV
PWVVSAKSAA ALDAQIERLA AFASRDRTDG VDAGAVDAGA VDAGAVARVL AGGRAQFEHR
AVVVGSGPDD LAAALAAPEG LVRGVASGVG RVAFVFPGQG TQWAGMGAEL LDSSAVFAAA
MAECEAALSP YVDWSLEAVV RQAPGAPTLE RVDVVQPVTF AVMVSLARVW QHHGVTPQAV
VGHSQGEIAA AYVAGALSLD DAARVVTLRS KSIAAHLAGK GGMLSLALSE DAVLERLAGF
DGLSVAAVNG PTATVVSGDP VQIEELARAC EADGVRARVI PVDYASHSRQ VEIIESELAE
VLAGLSPQAP RVPFFSTLEG AWITEPVLDG GYWYRNLRHR VGFAPAVETL ATDEGFTHFV
EVSAHPVLTM ALPGTVTGLA TLRRDNGGQD RLVASLAEAW ANGLAVDWSP LLPSATGHHS
DLPTYAFQTE RHWLGEIEAL APAGEPAVQP AVLRTEAAEP AELDRDEQLR VILDKVRAQT
AQVLGYATGG QIEVDRTFRE AGCTSLTGVD LRNRINAAFG VRMAPSMIFD FPTPEALAEQ
LLLVVHGEAA ANPAGAEPAP VAAAGAVDEP VAIVGMACRL PGGVASPEDL WRLVAGGGDA
ISEFPQDRGW DVEGLYHPDP EHPGTSYVRQ GGFIENVAGF DAAFFGISPR EALAMDPQQR
LLLETSWEAV EDAGIDPTSL RGRQVGVFTG AMTHEYGPSL RDGGEGLDGY LLTGNTASVM
SGRVSYTLGL EGPALTVDTA CSSSLVALHL AVQALRKGEV DMALAGGVAV MPTPGMFVEF
SRQRGLAGDG RSKAFAASAD GTSWSEGVGV LLVERLSDAR RNGHQVLAVV RGSALNQDGA
SNGLTAPNGP SQQRVIRRAL ADARLTTSDV DVVEAHGTGT RLGDPIEAQA LIATYGQGRD
DEQPLRLGSL KSNIGHTQAA AGVSGVIKMV QAMRHGLLPK TLHVDEPSDQ IDWSAGAVEL
LTEAVDWPEK QDGGLRRAAV SSFGISGTNA HVVLEEAPVV VEGASVVEPS VGGSAVGGGV
TPWVVSAKSA AALDAQIERL AAFASRDRTD DADAGAVDAG AVAHVLADGR AQFEHRAVAL
GAGADDLVQA LADPDGLIRG TASGVGRVAF VFPGQGTQWA GMGAELLDSS AVFAAAMAEC
EAALSPYVDW SLEAVVRQAP GAPTLERVDV VQPVTFAVMV SLARVWQHHG VTPQAVVGHS
QGEIAAAYVA GALPLDDAAR VVTLRSKSIA AHLAGKGGML SLALNEDAVL ERLSDFDGLS
VAAVNGPTAT VVSGDPVQIE ELAQACKADG FRARIIPVDY ASHSRQVEII ESELAQVLAG
LSPQAPRVPF FSTLEGTWIT EPVLDGTYWY RNLRHRVGFA PAIETLAVDE GFTHFVEVSA
HPVLTMTLPE TVTGLGTLRR EQGGQERLVT SLAEAWVNGL PVAWTSLLPA TASRPGLPTY
AFQAERYWLE NTPAALATGD DWRYRIDWKR LPAAEGSERT GLSGRWLAVT PEDHSAQAAA
VLTALVDAGA KVEVLTAGAD DDREALAARL TALTTGDGFT GVVSLLDGLV PQVAWVQALG
DAGIKAPLWS VTQGAVSVGR LDTPADPDRA MLWGLGRVVA LEHPERWAGL VDLPAQPDAA
ALAHLVTALS GATGEDQIAI RTTGLHARRL ARAPLHGRRP TRDWQPHGTV LITGGTGALG
SHAARWMAHH GAEHLLLVSR SGEQAPGATQ LTAELTASGA RVTIAACDVA DPHAMRTLLD
AIPAETPLTA VVHTAGALDD GIVDTLTAEQ VRRAHRAKAV GASVLDELTR DLDLDAFVLF
SSVSSTLGIP GQGNYAPHNA YLDALAARRR ATGRSAVSVA WGPWDGGGMA AGDGVAERLR
NHGVPGMDPE LALAALESAL GRDETAITVA DIDWDRFYLA YSSGRPQPLV EELPEVRRII
DARDSATSGQ GGSSAQGANP LAERLAAAAP GERTEILLGL VRAQAAAVLR MRSPEDVAAD
RAFKDIGFDS LAGVELRNRL TRATGLQLPA TLVFDHPTPL ALVSLLRSEF LGDEETADAR
RSAALPATVG AGAGAGAGTD ADDDPIAIVA MSCRYPGDIR SPEDLWRMLS EGGEGITPFP
TDRGWDLDGL YDADPDALGR AYVREGGFLH DAAEFDAEFF GVSPREALAM DPQQRMLLTT
SWEAFERAGI EPASLRGSST GVFIGLSYQD YAARVPNAPR GVEGYLLTGS TPSVASGRIA
YTFGLEGPAT TVDTACSSSL TALHLAVRAL RSGECTMALA GGVAMMATPH MFVEFSRQRA
LAPDGRSKAF SADADGFGAA EGVGLLLVER LSDARRNGHP VLAVVRGTAV NQDGASNGLT
APNGPSQQRV IRQALADARL APGDIDAVET HGTGTSLGDP IEAQGLQATY GKERPAERPL
AIGSVKSNIG HTQAAAGAAG IIKMVLAMRH GTLPKTLHAD EPSPHVDWAN SGLALVTEPI
DWPAGTGPRR AAVSSFGISG TNAHVVLEQA PDAAGEVLGA DEVPEVSETV AMAGTAGTSE
VAEGSEASEA PAAPGSREAS LPGHLPWVLS AKDEQSLRGQ AAALHAWLSE PAADLSDADG
PARLRDVGYT LATSRTAFAH RAAVTAADRD GFLDGLATLA QGGTSAHVHL DTARDGTTAF
LFTGQGSQRP GAGRELYDRH PVFARALDEI CAHLDGHLEL PLLDVMFAAE GSAEAALLDE
TRYTQCALFA LEVALFRLVE SWGMRPAALL GHSVGEIAAA HVAGVFSLAD AARLVAARGR
LMQELPAGGA MLAVQAAEDE IRVWLETEER YAGRLDVAAV NGPEAAVLSG DADAAREAEA
YWSGLGRRTR ALRVSHAFHS AHMDGMLDGF RAVLETVEFR RPSLTVVSNV TGLAAGPDDL
CDPEYWVRHV RGTVRFLDGV RVLRDLGVRT CLELGPDGVL TAMAADGLAD TPADSAAGSP
VGSPAGSPAD SAAGALRPRP LLVALLRRKR SETETVADAL GRAHAHGTGP DWHAWFAGSG
AHRVDLPTYS FRRDRYWLDA PAADTAVDTA GLGLGTADHP LLGAVVSLPD RDGLLLTGRL
SLRTHPWLAD HAVLGSVLLP GAAMVELAAH AAESAGLRDV RELTLLEPLV LPEHGGVELR
VTVGAPAGEP GGESAGDGAR PVSLHSRLAD APAGTAWSCH ATGLLATDRP ELPVAPDRAA
MWPPQGAEEV PLDGLYERLD GNGLAFGPLF QGLNAVWRYE GEVFADIALP ATTNATAPAT
ANGGGSAAAA PYGIHPALLD ASLHAIAVGG LVDEPELVRV PFHWSGVTVH AAGAAAARVR
LASAGTDAVS LSLTDGEGRP LVSVERLTLR PVTADQAAAS RVGGLMHRVA WRPYALASSG
EQDPHATSYG PTAVLGKDEL KVAAALESAG VEVGLYPDLA ALSQDVAAGA PAPRTVLAPL
PAGPADGGAE GVRGTVARTL ELLQAWLADE HLAGTRLLLV TRGAVRDPEG SGADDGGEDL
SHAAAWGLVR TAQTENPGRF GLLDLADDAS SYRTLPSVLS DAGLRDEPQL ALHDGTIRLA
RLASVRPETG TAAPALAPEG TVLLTGGTGG LGGLVARHVV GEWGVRRLLL VSRRGTDAPG
ADELVHELEA LGADVSVAAC DVADREALTA VLDAIPAEHP LTAVVHTAGV LSDGTLPSMT
TEDVEHVLRP KVDAAFLLDE LTSTPAYDLA AFVMFSSAAA VFGGAGQGAY AAANATLDAL
AWRRRAAGLP ALSLGWGLWA ETSGMTGELG QADLRRMSRA GIGGISDAEG IALLDAALRD
DRHPVLLPLR LDAAGLRDAA GNDPAGIPAL FRDVVGARTV RARPSAASAS TTAGTAGTPG
TADGAAETAA VTLADRAATV DGPARQRLLL EFVVGEVAEV LGHARGHRID AERGFLDLGF
DSLTAVELRN RLNSAGGLAL PATLVFDHPS PAALASHLDA ELPRGASDQD GAGNRNGNEN
GTTASRSTAE TDALLAQLTR LEGALVLTGL SDAPGSEEVL EHLRSLRSMV TGETGTGTAS
GAPDGAGSGA EDRPWAAGDG AGGGSEDGAG VPDFMNASAE ELFGLLDQDP STD
