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 27-MAR-2024, entry version 118. 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; Actinomycetota; Actinomycetes; Kitasatosporales; OC Streptomycetaceae; 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}. 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; AF079138; AAC69329.1; -; Genomic_DNA. DR PIR; T17409; T17409. DR PDB; 7UWR; EM; 2.61 A; A/B=89-974. DR PDB; 8CZC; EM; 2.86 A; B=628-942. DR PDBsum; 7UWR; -. DR PDBsum; 8CZC; -. DR EMDB; EMD-26839; -. DR EMDB; EMD-27094; -. DR SMR; Q9ZGI5; -. DR KEGG; ag:AAC69329; -. DR BioCyc; MetaCyc:MONOMER-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 CDD; cd08952; KR_1_SDR_x; 1. DR CDD; cd08956; KR_3_FAS_SDR_x; 1. DR CDD; cd00833; PKS; 3. DR Gene3D; 3.30.70.3290; -; 3. DR Gene3D; 3.40.47.10; -; 3. DR Gene3D; 1.10.1200.10; ACP-like; 3. DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 3. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2. DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 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; 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; IPR042104; PKS_dehydratase_sf. DR InterPro; IPR020807; PKS_DH. DR InterPro; IPR049551; PKS_DH_C. DR InterPro; IPR049552; PKS_DH_N. 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 PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1. DR PANTHER; PTHR43775:SF51; PHENOLPHTHIOCEROL_PHTHIOCEROL POLYKETIDE SYNTHASE SUBUNIT E; 1. 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; PF21089; PKS_DH_N; 1. 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; SM00822; PKS_KR; 2. DR SMART; SM00825; PKS_KS; 3. DR SMART; SM00823; PKS_PP; 3. DR SMART; SM01294; PKS_PP_betabranch; 3. DR SUPFAM; SSF47336; ACP-like; 3. DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 3. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 4. DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 3. DR SUPFAM; SSF53901; Thiolase-like; 3. DR PROSITE; PS50075; CARRIER; 3. DR PROSITE; PS00606; KS3_1; 2. DR PROSITE; PS52004; KS3_2; 3. DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2. DR PROSITE; PS52019; PKS_MFAS_DH; 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..4613 FT /note="Narbonolide/10-deoxymethynolide synthase PikA1, FT modules 1 and 2" FT /id="PRO_0000436357" FT DOMAIN 88..515 FT /note="Ketosynthase family 3 (KS3) 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT DOMAIN 1007..1085 FT /note="Carrier 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258" FT DOMAIN 1108..1536 FT /note="Ketosynthase family 3 (KS3) 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT DOMAIN 2495..2570 FT /note="Carrier 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258" FT DOMAIN 2603..3029 FT /note="Ketosynthase family 3 (KS3) 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT DOMAIN 3579..3878 FT /note="PKS/mFAS DH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363" 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 634..917 FT /note="Acyltransferase 1" FT /evidence="ECO:0000305" FT REGION 1111..2567 FT /note="Module 1" 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 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 3579..3712 FT /note="N-terminal hotdog fold" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363" FT REGION 3727..3878 FT /note="C-terminal hotdog fold" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363" 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 1 activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348, FT ECO:0000305|PubMed:19437523" FT ACT_SITE 1416 FT /note="For beta-ketoacyl synthase 1 activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT ACT_SITE 1456 FT /note="For beta-ketoacyl synthase 1 activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" 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 2 activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT ACT_SITE 2911 FT /note="For beta-ketoacyl synthase 2 activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT ACT_SITE 2951 FT /note="For beta-ketoacyl synthase 2 activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" 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 3611 FT /note="Proton acceptor; for dehydratase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363" FT ACT_SITE 3800 FT /note="Proton donor; for dehydratase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363" 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" FT STRAND 91..100 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 103..105 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 106..114 FT /evidence="ECO:0007829|PDB:7UWR" FT TURN 125..127 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 131..133 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 148..150 FT /evidence="ECO:0007829|PDB:7UWR" FT TURN 153..156 FT /evidence="ECO:0007829|PDB:7UWR" FT TURN 160..164 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 167..172 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 175..190 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 195..198 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 203..208 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 213..220 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 230..234 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 237..247 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 253..257 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 259..261 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 262..275 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 280..288 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 293..302 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 326..334 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 335..340 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 347..356 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 368..381 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 386..388 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 389..393 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 402..413 FT /evidence="ECO:0007829|PDB:7UWR" FT TURN 414..417 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 424..427 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 430..433 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 437..439 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 440..454 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 464..466 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 472..475 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 477..479 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 496..502 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 506..515 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 540..548 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 549..563 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 583..592 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 598..607 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 608..615 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 618..620 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 621..625 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 630..636 FT /evidence="ECO:0007829|PDB:7UWR" FT TURN 644..647 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 648..653 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 655..672 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 676..680 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 692..712 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 718..722 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 726..733 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 739..756 FT /evidence="ECO:0007829|PDB:7UWR" FT TURN 757..760 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 762..768 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 770..776 FT /evidence="ECO:0007829|PDB:7UWR" FT TURN 777..779 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 783..790 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 793..798 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 800..812 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 817..821 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 830..834 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 835..841 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 854..856 FT /evidence="ECO:0007829|PDB:7UWR" FT TURN 857..860 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 861..863 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 870..878 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 883..892 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 896..901 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 903..905 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 909..911 FT /evidence="ECO:0007829|PDB:7UWR" FT STRAND 916..919 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 929..940 FT /evidence="ECO:0007829|PDB:7UWR" FT TURN 941..943 FT /evidence="ECO:0007829|PDB:7UWR" FT HELIX 949..951 FT /evidence="ECO:0007829|PDB:7UWR" 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 //