PIKA2_STRVZ
ID PIKA2_STRVZ Reviewed; 3739 AA.
AC Q9ZGI4;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Narbonolide/10-deoxymethynolide synthase PikA2, modules 3 and 4 {ECO:0000305};
DE EC=2.3.1.239 {ECO:0000269|PubMed:10421766, ECO:0000305|PubMed:21570406};
DE EC=2.3.1.240 {ECO:0000269|PubMed:10421766, ECO:0000305|PubMed:21570406};
DE AltName: Full=Narbonolide/10-deoxymethynolide synthase PikAII {ECO:0000305};
DE AltName: Full=Pikromycin polyketide synthase component PikAII {ECO:0000303|PubMed:10421766};
DE Short=Pikromycin PKS component PikAII {ECO:0000303|PubMed:10421766};
DE AltName: Full=Type I modular polyketide synthase PikAII {ECO:0000303|PubMed:10421766};
DE Short=PKS {ECO:0000303|PubMed:10421766};
GN Name=pikAII {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], AND PATHWAY.
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, PATHWAY, 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).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 920-1423, FUNCTION, CATALYTIC
RP ACTIVITY, REACTION MECHANISM, COFACTOR, ACTIVE SITE, AND SUBUNIT.
RX PubMed=21570406; DOI=10.1016/j.jmb.2011.04.065;
RA Zheng J., Keatinge-Clay A.T.;
RT "Structural and functional analysis of C2-type ketoreductases from modular
RT polyketide synthases.";
RL J. Mol. Biol. 410:105-117(2011).
CC -!- FUNCTION: Involved in the biosynthesis of 12- and 14-membered ring
CC macrolactone antibiotics such as methymycin/neomethymycin and
CC pikromycin/narbomycin, respectively. Component of the pikromycin PKS
CC which catalyzes the biosynthesis of both precursors 10-deoxymethynolide
CC (12-membered ring macrolactone) and narbonolide (14-membered ring
CC macrolactone). Chain elongation through PikAI, PikAII and PikAIII
CC followed by thioesterase catalyzed termination results in the
CC production of 10-deoxymethynolide, while continued elongation through
CC PikAIV, followed by thioesterase (TE) catalyzed cyclization results in
CC the biosynthesis of the narbonolide. {ECO:0000269|PubMed:10421766,
CC ECO:0000269|PubMed:21570406, 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:21570406};
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:21570406};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305|PubMed:21570406};
CC Note=Binds 2 phosphopantetheines covalently. {ECO:0000305};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:19027305,
CC ECO:0000305|PubMed:9770448}.
CC -!- SUBUNIT: Homodimer (PubMed:21570406). 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:0000269|PubMed:21570406,
CC ECO:0000305|PubMed:19027305}.
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, ECO:0000305|PubMed:21570406}.
CC -!- MISCELLANEOUS: C2-type beta-ketoacyl reductase 1 is unable to bind NADP
CC and seems to act as a racemase. {ECO:0000269|PubMed:21570406}.
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DR EMBL; AF079138; AAC69330.1; -; Genomic_DNA.
DR PIR; T17410; T17410.
DR PDB; 3QP9; X-ray; 1.88 A; A/B/C/D=920-1423.
DR PDBsum; 3QP9; -.
DR SMR; Q9ZGI4; -.
DR KEGG; ag:AAC69330; -.
DR BioCyc; MetaCyc:MON-18412; -.
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:0016491; F:oxidoreductase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; TAS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 2.
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; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
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; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR015083; Polyketide_synth_docking.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR002364; Quin_OxRdtase/zeta-crystal_CS.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 2.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF08990; Docking; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 2.
DR Pfam; PF00109; ketoacyl-synt; 2.
DR Pfam; PF02801; Ketoacyl-synt_C; 2.
DR Pfam; PF08659; KR; 2.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 2.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 2.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 5.
DR SUPFAM; SSF52151; SSF52151; 2.
DR SUPFAM; SSF53901; SSF53901; 2.
DR SUPFAM; SSF55048; SSF55048; 2.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 2.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
DR PROSITE; PS01162; QOR_ZETA_CRYSTAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Antibiotic biosynthesis;
KW Multifunctional enzyme; NADP; Phosphopantetheine; Phosphoprotein; Repeat;
KW Transferase.
FT CHAIN 1..3739
FT /note="Narbonolide/10-deoxymethynolide synthase PikA2,
FT modules 3 and 4"
FT /id="PRO_0000436358"
FT DOMAIN 1445..1520
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3570..3645
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 38..1517
FT /note="Module 3"
FT /evidence="ECO:0000305"
FT REGION 38..466
FT /note="Beta-ketoacyl synthase 1"
FT /evidence="ECO:0000305"
FT REGION 572..877
FT /note="Acyltransferase 1"
FT /evidence="ECO:0000305"
FT REGION 1150..1343
FT /note="C2-type beta-ketoacyl reductase 1"
FT /evidence="ECO:0000305|PubMed:21570406"
FT REGION 1542..3642
FT /note="Module 4"
FT /evidence="ECO:0000305"
FT REGION 1542..1970
FT /note="Beta-ketoacyl synthase 2"
FT /evidence="ECO:0000305"
FT REGION 2069..2374
FT /note="Acyltransferase 2"
FT /evidence="ECO:0000305"
FT REGION 2428..2703
FT /note="Dehydratase"
FT /evidence="ECO:0000305"
FT REGION 2959..3267
FT /note="Enoyl reductase"
FT /evidence="ECO:0000305"
FT REGION 3277..3458
FT /note="Beta-ketoacyl reductase 2"
FT /evidence="ECO:0000305"
FT ACT_SITE 208
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 1 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 662
FT /note="Acyl-ester intermediate; for acyltransferase 1
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1313
FT /note="For C2-type beta-ketoacyl reductase 1 and probable
FT racemase activities"
FT /evidence="ECO:0000250|UniProtKB:Q03132,
FT ECO:0000305|PubMed:21570406"
FT ACT_SITE 1712
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2159
FT /note="Acyl-ester intermediate; for acyltransferase 2
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2460
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132"
FT ACT_SITE 2629
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132"
FT ACT_SITE 3005
FT /note="For enoyl reductase activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132"
FT ACT_SITE 3427
FT /note="For beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000305"
FT BINDING 3092..3109
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /ligand_note="for enoyl reductase activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132"
FT BINDING 3285..3288
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 3309..3312
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 3338..3339
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 3388
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:0000250|UniProtKB:Q03131"
FT BINDING 3412..3413
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 1480
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3605
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT HELIX 924..926
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 927..934
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 948..955
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 956..958
FT /evidence="ECO:0007829|PDB:3QP9"
FT TURN 960..962
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 963..971
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 975..981
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 987..1000
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1006..1010
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1012..1014
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1028..1042
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1049..1055
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1068..1083
FT /evidence="ECO:0007829|PDB:3QP9"
FT TURN 1085..1087
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1088..1094
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1100..1110
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1117..1122
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1125..1133
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1150..1156
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1160..1172
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1176..1181
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1202..1211
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1214..1219
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1225..1233
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1241..1246
FT /evidence="ECO:0007829|PDB:3QP9"
FT TURN 1256..1258
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1261..1284
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1294..1300
FT /evidence="ECO:0007829|PDB:3QP9"
FT TURN 1301..1305
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1311..1324
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1333..1339
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1346..1348
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1351..1358
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1366..1379
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1382..1386
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1391..1399
FT /evidence="ECO:0007829|PDB:3QP9"
FT STRAND 1400..1402
FT /evidence="ECO:0007829|PDB:3QP9"
FT TURN 1406..1409
FT /evidence="ECO:0007829|PDB:3QP9"
FT HELIX 1411..1414
FT /evidence="ECO:0007829|PDB:3QP9"
SQ SEQUENCE 3739 AA; 387178 MW; 3D3910824DA5B080 CRC64;
MSTVNEEKYL DYLRRATADL HEARGRLREL EAKAGEPVAI VGMACRLPGG VASPEDLWRL
VAGGEDAISE FPQDRGWDVE GLYDPNPEAT GKSYAREAGF LYEAGEFDAD FFGISPREAL
AMDPQQRLLL EASWEAFEHA GIPAATARGT SVGVFTGVMY HDYATRLTDV PEGIEGYLGT
GNSGSVASGR VAYTLGLEGP AVTVDTACSS SLVALHLAVQ ALRKGEVDMA LAGGVTVMST
PSTFVEFSRQ RGLAPDGRSK SFSSTADGTS WSEGVGVLLV ERLSDARRKG HRILAVVRGT
AVNQDGASSG LTAPNGPSQQ RVIRRALADA RLTTSDVDVV EAHGTGTRLG DPIEAQAVIA
TYGQGRDGEQ PLRLGSLKSN IGHTQAAAGV SGVIKMVQAM RHGVLPKTLH VEKPTDQVDW
SAGAVELLTE AMDWPDKGDG GLRRAAVSSF GVSGTNAHVV LEEAPAAEET PASEATPAVE
PSVGAGLVPW LVSAKTPAAL DAQIGRLAAF ASQGRTDAAD PGAVARVLAG GRAEFEHRAV
VLGTGQDDFA QALTAPEGLI RGTPSDVGRV AFVFPGQGTQ WAGMGAELLD VSKEFAAAMA
ECESALSRYV DWSLEAVVRQ APGAPTLERV DVVQPVTFAV MVSLAKVWQH HGVTPQAVVG
HSQGEIAAAY VAGALTLDDA ARVVTLRSKS IAAHLAGKGG MISLALSEEA TRQRIENLHG
LSIAAVNGPT ATVVSGDPTQ IQELAQACEA DGVRARIIPV DYASHSAHVE TIESELAEVL
AGLSPRTPEV PFFSTLEGAW ITEPVLDGTY WYRNLRHRVG FAPAVETLAT DEGFTHFIEV
SAHPVLTMTL PETVTGLGTL RREQGGQERL VTSLAEAWTN GLTIDWAPVL PTATGHHPEL
PTYAFQRRHY WLHDSPAVQG SVQDSWRYRI DWKRLAVADA SERAGLSGRW LVVVPEDRSA
EAAPVLAALS GAGADPVQLD VSPLGDRQRL AATLGEALAA AGGAVDGVLS LLAWDESAHP
GHPAPFTRGT GATLTLVQAL EDAGVAAPLW CVTHGAVSVG RADHVTSPAQ AMVWGMGRVA
ALEHPERWGG LIDLPSDADR AALDRMTTVL AGGTGEDQVA VRASGLLARR LVRASLPAHG
TASPWWQADG TVLVTGAEEP AAAEAARRLA RDGAGHLLLH TTPSGSEGAE GTSGAAEDSG
LAGLVAELAD LGATATVVTC DLTDAEAAAR LLAGVSDAHP LSAVLHLPPT VDSEPLAATD
ADALARVVTA KATAALHLDR LLREAAAAGG RPPVLVLFSS VAAIWGGAGQ GAYAAGTAFL
DALAGQHRAD GPTVTSVAWS PWEGSRVTEG ATGERLRRLG LRPLAPATAL TALDTALGHG
DTAVTIADVD WSSFAPGFTT ARPGTLLADL PEARRALDEQ QSTTAADDTV LSRELGALTG
AEQQRRMQEL VREHLAVVLN HPSPEAVDTG RAFRDLGFDS LTAVELRNRL KNATGLALPA
TLVFDYPTPR TLAEFLLAEI LGEQAGAGEQ LPVDGGVDDE PVAIVGMACR LPGGVASPED
LWRLVAGGED AISGFPQDRG WDVEGLYDPD PDASGRTYCR AGGFLDEAGE FDADFFGISP
REALAMDPQQ RLLLETSWEA VEDAGIDPTS LQGQQVGVFA GTNGPHYEPL LRNTAEDLEG
YVGTGNAASI MSGRVSYTLG LEGPAVTVDT ACSSSLVALH LAVQALRKGE CGLALAGGVT
VMSTPTTFVE FSRQRGLAED GRSKAFAASA DGFGPAEGVG MLLVERLSDA RRNGHRVLAV
VRGSAVNQDG ASNGLTAPNG PSQQRVIRRA LADARLTTAD VDVVEAHGTG TRLGDPIEAQ
ALIATYGQGR DTEQPLRLGS LKSNIGHTQA AAGVSGIIKM VQAMRHGVLP KTLHVDRPSD
QIDWSAGTVE LLTEAMDWPR KQEGGLRRAA VSSFGISGTN AHIVLEEAPV DEDAPADEPS
VGGVVPWLVS AKTPAALDAQ IGRLAAFASQ GRTDAADPGA VARVLAGGRA QFEHRAVALG
TGQDDLAAAL AAPEGLVRGV ASGVGRVAFV FPGQGTQWAG MGAELLDVSK EFAAAMAECE
AALAPYVDWS LEAVVRQAPG APTLERVDVV QPVTFAVMVS LAKVWQHHGV TPQAVVGHSQ
GEIAAAYVAG ALSLDDAARV VTLRSKSIGA HLAGQGGMLS LALSEAAVVE RLAGFDGLSV
AAVNGPTATV VSGDPTQIQE LAQACEADGV RARIIPVDYA SHSAHVETIE SELADVLAGL
SPQTPQVPFF STLEGAWITE PALDGGYWYR NLRHRVGFAP AVETLATDEG FTHFVEVSAH
PVLTMALPET VTGLGTLRRD NGGQHRLTTS LAEAWANGLT VDWASLLPTT TTHPDLPTYA
FQTERYWPQP DLSAAGDITS AGLGAAEHPL LGAAVALADS DGCLLTGSLS LRTHPWLADH
AVAGTVLLPG TAFVELAFRA GDQVGCDLVE ELTLDAPLVL PRRGAVRVQL SVGASDESGR
RTFGLYAHPE DAPGEAEWTR HATGVLAARA DRTAPVADPE AWPPPGAEPV DVDGLYERFA
ANGYGYGPLF QGVRGVWRRG DEVFADVALP AEVAGAEGAR FGLHPALLDA AVQAAGAGRG
VRRGHAAAVR LERDLLYAVG ATALRVRLAP AGPDTVSVSA ADSSGQPVFA ADSLTVLPVD
PAQLAAFSDP TLDALHLLEW TAWDGAAQAL PGAVVLGGDA DGLAAALRAG GTEVLSFPDL
TDLVEAVDRG ETPAPATVLV ACPAAGPDGP EHVREALHGS LALMQAWLAD ERFTDGRLVL
VTRDAVAARS GDGLRSTGQA AVWGLGRSAQ TESPGRFVLL DLAGEARTAG DATAGDGLTT
GDATVGGTSG DAALGSALAT ALGSGEPQLA LRDGALLVPR LARAAAPAAA DGLAAADGLA
ALPLPAAPAL WRLEPGTDGS LESLTAAPGD AETLAPEPLG PGQVRIAIRA TGLNFRDVLI
ALGMYPDPAL MGTEGAGVVT ATGPGVTHLA PGDRVMGLLS GAYAPVVVAD ARTVARMPEG
WTFAQGASVP VVFLTAVYAL RDLADVKPGE RLLVHSAAGG VGMAAVQLAR HWGVEVHGTA
SHGKWDALRA LGLDDAHIAS SRTLDFESAF RAASGGAGMD VVLNSLAREF VDASLRLLGP
GGRFVEMGKT DVRDAERVAA DHPGVGYRAF DLGEAGPERI GEMLAEVIAL FEDGVLRHLP
VTTWDVRRAR DAFRHVSQAR HTGKVVLTMP SGLDPEGTVL LTGGTGALGG IVARHVVGEW
GVRRLLLVSR RGTDAPGAGE LVHELEALGA DVSVAACDVA DREALTAVLD SIPAEHPLTA
VVHTAGVLSD GTLPSMTAED VEHVLRPKVD AAFLLDELTS TPGYDLAAFV MFSSAAAVFG
GAGQGAYAAA NATLDALAWR RRTAGLPALS LGWGLWAETS GMTGGLSDTD RSRLARSGAT
PMDSELTLSL LDAAMRRDDP ALVPIALDVA ALRAQQRDGM LAPLLSGLTR GSRVGGAPVN
QRRAAAGGAG EADTDLGGRL AAMTPDDRVA HLRDLVRTHV ATVLGHGTPS RVDLERAFRD
TGFDSLTAVE LRNRLNAATG LRLPATLVFD HPTPGELAGH LLDELATAAG GSWAEGTGSG
DTASATDRQT TAALAELDRL EGVLASLAPA AGGRPELAAR LRALAAALGD DGDDATDLDE
ASDDDLFSFI DKELGDSDF
