ERYA3_SACER
ID ERYA3_SACER Reviewed; 3172 AA.
AC Q03133; Q54097; Q99270;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=6-deoxyerythronolide-B synthase EryA3, modules 5 and 6 {ECO:0000305};
DE Short=DEBS 3 {ECO:0000303|PubMed:1740151};
DE EC=2.3.1.94 {ECO:0000269|PubMed:21095573};
DE AltName: Full=6-deoxyerythronolide B synthase III {ECO:0000303|PubMed:1740151};
DE AltName: Full=Erythronolide synthase;
DE AltName: Full=ORF C {ECO:0000303|PubMed:1740151};
GN Name=eryA {ECO:0000303|PubMed:1740151};
OS Saccharopolyspora erythraea (Streptomyces erythraeus).
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Saccharopolyspora.
OX NCBI_TaxID=1836;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBUNIT.
RC STRAIN=ATCC 11635 / DSM 40517 / IFO 13426 / JCM 4026 / NCIB 8594;
RX PubMed=2234082; DOI=10.1038/348176a0;
RA Cortes J., Haydock S.F., Roberts G.A., Bevitt D.J., Leadlay P.F.;
RT "An unusually large multifunctional polypeptide in the erythromycin-
RT producing polyketide synthase of Saccharopolyspora erythraea.";
RL Nature 348:176-178(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBUNIT.
RX PubMed=2024119; DOI=10.1126/science.2024119;
RA Donadio S., Staver M.J., McAlpine J.B., Swanson S.J., Katz L.;
RT "Modular organization of genes required for complex polyketide
RT biosynthesis.";
RL Science 252:675-679(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 11635 / DSM 40517 / IFO 13426 / JCM 4026 / NCIB 8594;
RX PubMed=1740151; DOI=10.1111/j.1432-1033.1992.tb16603.x;
RA Bevitt D.J., Cortes J., Haydock S.F., Leadlay P.F.;
RT "6-deoxyerythronolide-B synthase 2 from Saccharopolyspora erythraea.
RT Cloning of the structural gene, sequence analysis and inferred domain
RT structure of the multifunctional enzyme.";
RL Eur. J. Biochem. 204:39-49(1992).
RN [4]
RP PROTEIN SEQUENCE OF 2-11.
RC STRAIN=CA340;
RX PubMed=1618327; DOI=10.1016/0014-5793(92)80624-p;
RA Caffrey P., Bevitt D.J., Staunton J., Leadlay P.F.;
RT "Identification of DEBS 1, DEBS 2 and DEBS 3, the multienzyme polypeptides
RT of the erythromycin-producing polyketide synthase from Saccharopolyspora
RT erythraea.";
RL FEBS Lett. 304:225-228(1992).
RN [5]
RP FUNCTION, PATHWAY, AND SUBUNIT.
RX PubMed=17328673; DOI=10.1146/annurev.biochem.76.053105.093515;
RA Khosla C., Tang Y., Chen A.Y., Schnarr N.A., Cane D.E.;
RT "Structure and mechanism of the 6-deoxyerythronolide B synthase.";
RL Annu. Rev. Biochem. 76:195-221(2007).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=21095573; DOI=10.1016/j.chembiol.2010.09.013;
RA Zhang H., Wang Y., Wu J., Skalina K., Pfeifer B.A.;
RT "Complete biosynthesis of erythromycin A and designed analogs using E. coli
RT as a heterologous host.";
RL Chem. Biol. 17:1232-1240(2010).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 2893-3172, ACTIVE SITE, AND
RP SUBUNIT.
RX PubMed=11752428; DOI=10.1073/pnas.011399198;
RA Tsai S.-C., Miercke L.J.W., Krucinski J., Gokhale R., Chen J.C.-H.,
RA Foster P.G., Cane D.E., Khosla C., Stroud R.M.;
RT "Crystal structure of the macrocycle-forming thioesterase domain of the
RT erythromycin polyketide synthase: versatility from a unique substrate
RT channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:14808-14813(2001).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 2890-3172, AND SUBUNIT.
RX PubMed=12379102; DOI=10.1021/bi0260177;
RA Tsai S.-C., Lu H., Cane D.E., Khosla C., Stroud R.M.;
RT "Insights into channel architecture and substrate specificity from crystal
RT structures of two macrocycle-forming thioesterases of modular polyketide
RT synthases.";
RL Biochemistry 41:12598-12606(2002).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS) OF 1-917, COFACTOR, ACTIVE SITE, AND
RP SUBUNIT.
RX PubMed=16844787; DOI=10.1073/pnas.0601924103;
RA Tang Y., Kim C.Y., Mathews I.I., Cane D.E., Khosla C.;
RT "The 2.7-Angstrom crystal structure of a 194-kDa homodimeric fragment of
RT the 6-deoxyerythronolide B synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11124-11129(2006).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 2904-3172 IN COMPLEX WITH
RP SUBSTRATE ANALOG, ACTIVITY REGULATION, AND ACTIVE SITE.
RX PubMed=26592346; DOI=10.1016/j.bbagen.2015.11.007;
RA Argyropoulos P., Bergeret F., Pardin C., Reimer J.M., Pinto A., Boddy C.N.,
RA Schmeing T.M.;
RT "Towards a characterization of the structural determinants of specificity
RT in the macrocyclizing thioesterase for deoxyerythronolide B biosynthesis.";
RL Biochim. Biophys. Acta 1860:486-497(2016).
CC -!- FUNCTION: Involved in the biosynthesis of antibiotic erythromycin via
CC the biosynthesis of its aglycone precursor, 6-deoxyerythronolide B (6-
CC dEB). {ECO:0000269|PubMed:21095573, ECO:0000305|PubMed:17328673}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6 (S)-methylmalonyl-CoA + 12 H(+) + 6 NADPH + propanoyl-CoA =
CC 6-deoxyerythronolide B + 6 CO2 + 7 CoA + H2O + 6 NADP(+);
CC Xref=Rhea:RHEA:23068, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16089, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57327, ChEBI:CHEBI:57392, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=2.3.1.94;
CC Evidence={ECO:0000269|PubMed:21095573};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305|PubMed:16844787};
CC Note=Binds 2 phosphopantetheines covalently. {ECO:0000305};
CC -!- ACTIVITY REGULATION: Inhibited by diphenyl phosphonates derivatives
CC such as diphenyl allylphosphonate. {ECO:0000269|PubMed:26592346}.
CC -!- PATHWAY: Antibiotic biosynthesis; erythromycin biosynthesis.
CC {ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:21095573}.
CC -!- SUBUNIT: Homodimer (PubMed:11752428, PubMed:12379102, PubMed:16844787).
CC Erythronolide synthase is composed of EryAI, EryAII and EryAIII
CC multimodular (2 modules) polypeptides each coding for a functional
CC synthase subunit which participates in 2 of the six FAS-like elongation
CC steps required for formation of the polyketide. Module 1, 2, 3, 4, 5,
CC and 6 participating in biosynthesis steps 1, 2, 3, 4, 5, and 6,
CC respectively. {ECO:0000269|PubMed:11752428,
CC ECO:0000269|PubMed:12379102, ECO:0000269|PubMed:16844787,
CC ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:1740151,
CC ECO:0000305|PubMed:2024119}.
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:17328673, ECO:0000305|PubMed:21095573}.
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DR EMBL; X56107; CAA39583.1; -; Genomic_DNA.
DR EMBL; M63677; AAA26495.1; -; Genomic_DNA.
DR EMBL; X62569; CAA44449.1; -; Genomic_DNA.
DR PIR; S13595; S13595.
DR PIR; S22012; S22012.
DR PDB; 1KEZ; X-ray; 2.80 A; A/B/C=2893-3172.
DR PDB; 1MO2; X-ray; 3.00 A; A/B=2893-3172.
DR PDB; 1PZR; NMR; -; A/B=1-39.
DR PDB; 2HG4; X-ray; 2.73 A; A/B/C/D/E/F=1-917.
DR PDB; 5D3K; X-ray; 1.70 A; A=2904-3172.
DR PDB; 5D3Z; X-ray; 2.10 A; A=2904-3172.
DR PDB; 6MLK; X-ray; 2.45 A; A=2893-3172.
DR PDB; 7M7E; EM; 3.20 A; A/B=2896-3172.
DR PDB; 7M7F; EM; 3.20 A; A/B=2896-3172.
DR PDB; 7M7G; EM; 4.10 A; A/B=2896-3172.
DR PDB; 7M7H; EM; 4.10 A; A/B=2896-3172.
DR PDBsum; 1KEZ; -.
DR PDBsum; 1MO2; -.
DR PDBsum; 1PZR; -.
DR PDBsum; 2HG4; -.
DR PDBsum; 5D3K; -.
DR PDBsum; 5D3Z; -.
DR PDBsum; 6MLK; -.
DR PDBsum; 7M7E; -.
DR PDBsum; 7M7F; -.
DR PDBsum; 7M7G; -.
DR PDBsum; 7M7H; -.
DR SMR; Q03133; -.
DR DIP; DIP-61229N; -.
DR ESTHER; sacer-ery3; Thioesterase.
DR PRIDE; Q03133; -.
DR ABCD; Q03133; 1 sequenced antibody.
DR BioCyc; MetaCyc:MON-17079; -.
DR BRENDA; 2.3.1.94; 5518.
DR UniPathway; UPA00240; -.
DR EvolutionaryTrace; Q03133; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0047879; F:erythronolide synthase activity; 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; -; 2.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 2.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
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; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR020802; PKS_thioesterase.
DR InterPro; IPR015083; Polyketide_synth_docking.
DR InterPro; IPR036299; Polyketide_synth_docking_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 2.
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; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 2.
DR SMART; SM00825; PKS_KS; 2.
DR SMART; SM00823; PKS_PP; 2.
DR SMART; SM00824; PKS_TE; 1.
DR SUPFAM; SSF101173; SSF101173; 1.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 4.
DR SUPFAM; SSF52151; SSF52151; 2.
DR SUPFAM; SSF53474; SSF53474; 1.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Antibiotic biosynthesis;
KW Direct protein sequencing; Multifunctional enzyme; NADP;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1618327"
FT CHAIN 2..3172
FT /note="6-deoxyerythronolide-B synthase EryA3, modules 5 and
FT 6"
FT /id="PRO_0000180295"
FT DOMAIN 1392..1467
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2819..2894
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 41..1464
FT /note="Module 5"
FT /evidence="ECO:0000305"
FT REGION 41..455
FT /note="Beta-ketoacyl synthase 1"
FT /evidence="ECO:0000305"
FT REGION 557..874
FT /note="Acyltransferase 1"
FT /evidence="ECO:0000305"
FT REGION 1117..1294
FT /note="Beta-ketoacyl reductase 1"
FT /evidence="ECO:0000305"
FT REGION 1492..2891
FT /note="Module 6"
FT /evidence="ECO:0000305"
FT REGION 1492..1919
FT /note="Beta-ketoacyl synthase 2"
FT /evidence="ECO:0000305"
FT REGION 2022..2331
FT /note="Acyltransferase 2"
FT /evidence="ECO:0000305"
FT REGION 2557..2731
FT /note="Beta-ketoacyl reductase 2"
FT /evidence="ECO:0000305"
FT REGION 2960..3166
FT /note="Thioesterase"
FT /evidence="ECO:0000305"
FT ACT_SITE 199
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 1 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022,
FT ECO:0000305|PubMed:16844787"
FT ACT_SITE 643
FT /note="Acyl-ester intermediate; for acyltransferase 1
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1264
FT /note="Acyl-ester intermediate; for beta-ketoacyl reductase
FT 1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q03132,
FT ECO:0000250|UniProtKB:Q9ZGI4"
FT ACT_SITE 1661
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2112
FT /note="Acyl-ester intermediate; for acyltransferase 2
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2701
FT /note="Acyl-ester intermediate; for beta-ketoacyl reductase
FT 2 activity"
FT /evidence="ECO:0000305"
FT ACT_SITE 3031
FT /note="Nucleophile; for thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q9ZGI2,
FT ECO:0000305|PubMed:11752428, ECO:0000305|PubMed:26592346"
FT ACT_SITE 3148
FT /note="Proton acceptor; for thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q9ZGI2,
FT ECO:0000305|PubMed:11752428, ECO:0000305|PubMed:26592346"
FT BINDING 1125..1128
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1148..1151
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1177..1178
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1229
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 1249..1250
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 2565..2568
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 2588..2591
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 2617..2618
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 2666
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 2686..2687
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 2965
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ZGI2"
FT BINDING 3032
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26592346"
FT BINDING 3058
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26592346"
FT SITE 644
FT /note="Important for discrimination between malonyl and
FT methylmalonyl polyketide chain extension units"
FT /evidence="ECO:0000305|PubMed:16844787"
FT SITE 744
FT /note="Important for discrimination between malonyl and
FT methylmalonyl polyketide chain extension units"
FT /evidence="ECO:0000305|PubMed:16844787"
FT MOD_RES 1427
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2854
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT CONFLICT 289
FT /note="A -> R (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 493..517
FT /note="PEPRNSLRDTGFTLATRASAMEHRA -> ASRGTRCATPVSRWPPAAAPWEQ
FT (in Ref. 1; CAA39583)"
FT /evidence="ECO:0000305"
FT CONFLICT 493
FT /note="P -> R (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="A -> R (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 513
FT /note="M -> W (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 525
FT /note="E -> D (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 536
FT /note="R -> G (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 547..551
FT /note="GPNSP -> ARTR (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 673
FT /note="R -> A (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 716
FT /note="Missing (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 734..736
FT /note="AHK -> GIT (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 896
FT /note="R -> RELPVYPFQRQR (in Ref. 1; CAA39583)"
FT /evidence="ECO:0000305"
FT CONFLICT 896
FT /note="R -> RQR (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 988..994
FT /note="GVAAVPH -> VSLLSRD (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1108..1116
FT /note="RTHPLEPLA -> ARTRWSPR (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1123..1125
FT /note="Missing (in Ref. 1; CAA39583)"
FT /evidence="ECO:0000305"
FT CONFLICT 1132
FT /note="L -> V (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1192
FT /note="A -> R (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1194
FT /note="Missing (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1277..1278
FT /note="AA -> RR (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1385..1390
FT /note="LCDGRE -> STAER (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1485
FT /note="Missing (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1518
FT /note="G -> R (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1601
FT /note="V -> L (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1724..1725
FT /note="LP -> FA (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1732
FT /note="Q -> L (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1739..1743
FT /note="GPAEG -> ARRA (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 1762
FT /note="T -> S (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 2252
FT /note="D -> DGAD (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 2275..2277
FT /note="QSP -> AVA (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 2408
FT /note="G -> GR (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 2420..2421
FT /note="LA -> S (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 2443..2444
FT /note="NA -> TH (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 2596
FT /note="A -> G (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 2609
FT /note="P -> A (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT CONFLICT 2715..2722
FT /note="RRAEGRAA -> AVRKAVRR (in Ref. 1; CAA39583)"
FT /evidence="ECO:0000305"
FT CONFLICT 2754
FT /note="D -> E (in Ref. 2; AAA26495)"
FT /evidence="ECO:0000305"
FT HELIX 10..38
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 41..50
FT /evidence="ECO:0007829|PDB:2HG4"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 57..65
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:2HG4"
FT TURN 93..96
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 107..112
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 115..130
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 143..149
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 163..168
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 169..173
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 175..186
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 192..196
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 201..214
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 219..227
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 233..238
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 265..273
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 274..279
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 286..295
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 300..303
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 307..321
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 341..350
FT /evidence="ECO:0007829|PDB:2HG4"
FT TURN 351..355
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 369..372
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 376..378
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 381..393
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 433..439
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 443..452
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 468..476
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 477..493
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 499..508
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 514..522
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 523..534
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 542..546
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 554..558
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 570..575
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 577..590
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 598..603
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 611..631
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 637..641
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 645..652
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 658..671
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 672..675
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 680..686
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 688..695
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 696..698
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 701..709
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 712..715
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 722..733
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 737..741
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 749..754
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 755..761
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 771..774
FT /evidence="ECO:0007829|PDB:2HG4"
FT TURN 777..779
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 785..787
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 790..798
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 803..812
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 817..820
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 822..824
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 828..838
FT /evidence="ECO:0007829|PDB:2HG4"
FT STRAND 846..848
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 858..869
FT /evidence="ECO:0007829|PDB:2HG4"
FT TURN 870..872
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 878..880
FT /evidence="ECO:0007829|PDB:2HG4"
FT HELIX 2906..2916
FT /evidence="ECO:0007829|PDB:5D3K"
FT HELIX 2920..2931
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 2939..2942
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 2948..2951
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 2954..2956
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 2958..2962
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 2966..2968
FT /evidence="ECO:0007829|PDB:1MO2"
FT HELIX 2971..2974
FT /evidence="ECO:0007829|PDB:5D3K"
FT HELIX 2975..2981
FT /evidence="ECO:0007829|PDB:5D3K"
FT TURN 2982..2984
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 2987..2990
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 3001..3004
FT /evidence="ECO:0007829|PDB:5D3K"
FT HELIX 3005..3020
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 3021..3023
FT /evidence="ECO:0007829|PDB:1MO2"
FT STRAND 3025..3030
FT /evidence="ECO:0007829|PDB:5D3K"
FT HELIX 3032..3046
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 3052..3058
FT /evidence="ECO:0007829|PDB:5D3K"
FT TURN 3062..3064
FT /evidence="ECO:0007829|PDB:1KEZ"
FT HELIX 3066..3070
FT /evidence="ECO:0007829|PDB:5D3K"
FT HELIX 3072..3081
FT /evidence="ECO:0007829|PDB:5D3K"
FT HELIX 3089..3104
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 3114..3121
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 3127..3129
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 3136..3138
FT /evidence="ECO:0007829|PDB:5D3K"
FT STRAND 3140..3146
FT /evidence="ECO:0007829|PDB:5D3K"
FT HELIX 3150..3152
FT /evidence="ECO:0007829|PDB:5D3K"
FT TURN 3153..3155
FT /evidence="ECO:0007829|PDB:5D3K"
FT HELIX 3156..3167
FT /evidence="ECO:0007829|PDB:5D3K"
SQ SEQUENCE 3172 AA; 331479 MW; DBBD5094E77DDD5F CRC64;
MSGDNGMTEE KLRRYLKRTV TELDSVTARL REVEHRAGEP IAIVGMACRF PGDVDSPESF
WEFVSGGGDA IAEAPADRGW EPDPDARLGG MLAAAGDFDA GFFGISPREA LAMDPQQRIM
LEISWEALER AGHDPVSLRG SATGVFTGVG TVDYGPRPDE APDEVLGYVG TGTASSVASG
RVAYCLGLEG PAMTVDTACS SGLTALHLAM ESLRRDECGL ALAGGVTVMS SPGAFTEFRS
QGGLAADGRC KPFSKAADGF GLAEGAGVLV LQRLSAARRE GRPVLAVLAG SAVNQDGASN
GLTAPSGPAQ QRVIRRALEN AGVRAGDVDY VEAHGTGTRL GDPIEVHALL STYGAERDPD
DPLWIGSVKS NIGHTQAAAG VAGVMKAVLA LRHGEMPRTL HFDEPSPQIE WDLGAVSVVS
QARSWPAGER PRRAGVSSFG ISGTNAHVIV EEAPEADEPE PAPDSGPVPL VLSGRDEQAM
RAQAGRLADH LAPEPRNSLR DTGFTLATRA SAMEHRAVVV GDRDEALAGL RAVADRRIAD
RTATGQGPNS PRRVAMVFPG QGAQWQGMAR DLLRESQVFA DSIRDCERAL APHVDWSLTD
LLSGARPLDR VDVVQPALFA VMVSLAALWR SHGVEPAAVV GHSQGEIAAA HVAGALTLED
AAKLVAVRSR VLRRLGGQGG MASFGLGTEQ AAERIGRFAG ALSIASVNGP RSVVVVAGES
GPLDELIAEC EAEAHKARRI PVDYASHSPQ VESLREELLT ELAGISPVSA DVALYSTTTG
QPIDTATMDT AYWYANLREQ VRFQDATRQL AEAGFDAFVE VSPHPVLTVG IEATLDSALP
ADAGACVVGT LRRDRGGLAD FHTALGEAYA QGVEVDWSPA FADARPVELP VYPFQRYWLP
IPTGGRARDE DDDWRYQVVW REAEWESASL AGRVLLVTGP GVPSELSDAI RSGLEQSGAT
VLTCDVESRS TIGTALEAAD TDALSTVGVA AVPHGEAVDP SLDALALVQA LGAAGVEAPL
WVLTRNAVQV ADGELVDPAQ AMVGGLGRVV GIEQPGRWGG LVDLVDADAA SIRSLAAVLA
DPRGEEQVAI RADGIKVARL VPAPARARTH PLEPLAGTVL VTGGTGGIGA HLARWLARSG
AEHLVLLGRR GADAPGASEL REELTALGTG VTIAACDVAD RARLEAVLAA EAAAEGRTVS
AVMHAAGVST STPLDDLTEA EFTEIADVKV RGTVNLDELC PDLDAFVLFS SNAGVWGSPG
LASYAAANAF LDGFARAARS EGAPVTSIAW GLWAGQNMAG DEGGEYLRSQ GLRAMDPDRA
VEELHITLDH GQTSVSVVDM DRRRFVELFT AARHRPLFDE IAGARAEARQ SEEGPALAQR
LAALLCDGRE REHLAHLIRA EVAAVLGHGD DAAIDRDRAF RDLGFDSMTA VDLRNRLAAV
TGVREAATVV FDHPTITRLA DHYLERLVGA AEAEQAPALV REVPPKDADD PIAIVGMACR
FPGGVHNPGE LWEFIVGGGD AVTEMPTDRG WDLDALFDPD PQRHGTSYSR HGAFLDGAAD
FDAAFFGISP REALAMDPQQ RQVLETTWEL FENAGIDPHS VRGSDTGVFL GAAYQGYGQD
AVVPEDSEGY LLTGNSSAVV SGRVAYVLGL EGPAVTVDTA CSSSLVALHS ACGSLRDGDC
GLAVAGGVSV MAGPEVFTEF SRQGGLAVDG RCKAFSAEAD GFGLPEGVAV VQLQRLSDGP
AEGGRQVLGV VAGSAINQDG ATNGLAAPSG VAQQRVIRKA WARAGITGAD VAVVEAHGTG
TRLGDPVEAS ALLATYGKSR GSSGPVLLGS VKSNIGHAQA AAGVAGVIKV VLGLNRGLVP
PMLCRGERSP LIEWSSGGVE LAEAVSPWPP AADGVRRAGV SAFGVSGTNA HVIIAEPPEP
EPLPEPGPVG VLAAANSVPV LLSARTETAL AAQARLLESA VDDSVPLTAL ASALATGRAH
LPRRAALLAG DHEQLRGQLR AVAEGVAAPG ATTGTASAGG VVFVFPGQGA QWEGMARGLL
SVPVFAESIA ECDAVLSEVA GFSASEVLEQ RPDAPSLERV DVVQPVLFSV MVSLARLWGA
CGVSPSAVIG HSQGEIAAAV VAGVLSLEDG VRVVALRAKA LRALAGKGGM VSLAAPGERA
RALIAPWEDR ISVAAVNSPS SVVVSGDPEA LAELVARCED EGVRAKTLPV DYASHSRHVE
EIRETILADL DGISARRAAI PLYSTLHGER RDMGPRYWYD NLRSQVRFDE AVSAQSPDGH
ATFVEMSPHP VLTAAVQEIA ADAVAIGSLH RDTAEEHLIA ELARAHVHGV AVDWRNVFPA
APPVALPNYP FEPQRYWLAP EVSDQLADSR YRVDWRPLAT TPVDLEGGFL VHGSAPESLT
SAVEKAGGVV PVASADREAL AAALREVPGE VAGVLSVHTG AANALALHQS LGEAGVRAPL
WLVTSRAVAL GESEPVDPEQ AMVWGLGRVM GLETPERWGG LVDLPAEPAP GDGEAFVACL
GADGHEDQVA IRDHARYGRR LVRAPLGTRE SSWEPAGTAL VTGGTGALGG HVARHLARCG
VEDLVLVSRR GVDAPAAAEL EAELVALGPK TTITACDVAD REQLSKLLEE LRGQGRPVRT
VVHTAGVPES RPLHEIGELE SVCAAKVTGA RLLDELCPDA ETFVLFSSGA GVWGSANLGA
YSAANAYLDA LAHRRRAEGR AATSVAWGAW AGEGMATGDL EGLTRRGLRP MAPDRAIRAL
HQALDNGDTC VSIADVDWEA FAVGFTAARP RPLLDELVTP AVGAVPAVQA APAREMTSQE
LLEFTHSHVA AILGHSSPDA VGQDQPFTEL GFDSLTAVGL RNQLQQATGL ALPATLVFEH
PTVRRLADHI GQQLDSGTPA REASSALRDG YRQAGVSGRV RSYLDLLAGL SDFREHFDGS
DGFSLDLVDM ADGPGEVTVI CCAGTAAISG PHEFTRLAGA LRGIAPVRAV PQPGYEEGEP
LPSSMAAVAA VQADAVIRTQ GDKPFVVAGH SAGALMAYAL ATELLDRGHP PRGVVLIDVY
PPGHQDAMNA WLEELTATLF DRETVRMDDT RLTALGAYDR LTGQWRPRET GLPTLLVSAG
EPMGPWPDDS WKPTWPFEHD TVAVPGDHFT MVQEHADAIA RHIDAWLGGG NS
