ID CYSG_ECOL6 Reviewed; 457 AA. AC Q8FCW8; DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 27-MAR-2024, entry version 120. DE RecName: Full=Siroheme synthase {ECO:0000255|HAMAP-Rule:MF_01646}; DE Includes: DE RecName: Full=Uroporphyrinogen-III C-methyltransferase {ECO:0000255|HAMAP-Rule:MF_01646}; DE Short=Urogen III methylase {ECO:0000255|HAMAP-Rule:MF_01646}; DE EC=2.1.1.107 {ECO:0000255|HAMAP-Rule:MF_01646}; DE AltName: Full=SUMT {ECO:0000255|HAMAP-Rule:MF_01646}; DE AltName: Full=Uroporphyrinogen III methylase {ECO:0000255|HAMAP-Rule:MF_01646}; DE Short=UROM {ECO:0000255|HAMAP-Rule:MF_01646}; DE Includes: DE RecName: Full=Precorrin-2 dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01646}; DE EC=1.3.1.76 {ECO:0000255|HAMAP-Rule:MF_01646}; DE Includes: DE RecName: Full=Sirohydrochlorin ferrochelatase {ECO:0000255|HAMAP-Rule:MF_01646}; DE EC=4.99.1.4 {ECO:0000255|HAMAP-Rule:MF_01646}; GN Name=cysG {ECO:0000255|HAMAP-Rule:MF_01646}; OrderedLocusNames=c4144; OS Escherichia coli O6:H1 (strain CFT073 / ATCC 700928 / UPEC). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Escherichia. OX NCBI_TaxID=199310; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=CFT073 / ATCC 700928 / UPEC; RX PubMed=12471157; DOI=10.1073/pnas.252529799; RA Welch R.A., Burland V., Plunkett G. III, Redford P., Roesch P., Rasko D., RA Buckles E.L., Liou S.-R., Boutin A., Hackett J., Stroud D., Mayhew G.F., RA Rose D.J., Zhou S., Schwartz D.C., Perna N.T., Mobley H.L.T., RA Donnenberg M.S., Blattner F.R.; RT "Extensive mosaic structure revealed by the complete genome sequence of RT uropathogenic Escherichia coli."; RL Proc. Natl. Acad. Sci. U.S.A. 99:17020-17024(2002). CC -!- FUNCTION: Multifunctional enzyme that catalyzes the SAM-dependent CC methylations of uroporphyrinogen III at position C-2 and C-7 to form CC precorrin-2 via precorrin-1. Then it catalyzes the NAD-dependent ring CC dehydrogenation of precorrin-2 to yield sirohydrochlorin. Finally, it CC catalyzes the ferrochelation of sirohydrochlorin to yield siroheme. CC {ECO:0000255|HAMAP-Rule:MF_01646}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 S-adenosyl-L-methionine + uroporphyrinogen III = H(+) + CC precorrin-2 + 2 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:32459, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57308, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:58827, ChEBI:CHEBI:59789; EC=2.1.1.107; CC Evidence={ECO:0000255|HAMAP-Rule:MF_01646}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NAD(+) + precorrin-2 = 2 H(+) + NADH + sirohydrochlorin; CC Xref=Rhea:RHEA:15613, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:58351, ChEBI:CHEBI:58827; EC=1.3.1.76; CC Evidence={ECO:0000255|HAMAP-Rule:MF_01646}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 H(+) + siroheme = Fe(2+) + sirohydrochlorin; CC Xref=Rhea:RHEA:24360, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, CC ChEBI:CHEBI:58351, ChEBI:CHEBI:60052; EC=4.99.1.4; CC Evidence={ECO:0000255|HAMAP-Rule:MF_01646}; CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis; CC precorrin-2 from uroporphyrinogen III: step 1/1. {ECO:0000255|HAMAP- CC Rule:MF_01646}. CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis; CC sirohydrochlorin from precorrin-2: step 1/1. {ECO:0000255|HAMAP- CC Rule:MF_01646}. CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme CC biosynthesis; precorrin-2 from uroporphyrinogen III: step 1/1. CC {ECO:0000255|HAMAP-Rule:MF_01646}. CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme CC biosynthesis; siroheme from sirohydrochlorin: step 1/1. CC {ECO:0000255|HAMAP-Rule:MF_01646}. CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme CC biosynthesis; sirohydrochlorin from precorrin-2: step 1/1. CC {ECO:0000255|HAMAP-Rule:MF_01646}. CC -!- SIMILARITY: In the N-terminal section; belongs to the precorrin-2 CC dehydrogenase / sirohydrochlorin ferrochelatase family. CC {ECO:0000255|HAMAP-Rule:MF_01646}. CC -!- SIMILARITY: In the C-terminal section; belongs to the precorrin CC methyltransferase family. {ECO:0000255|HAMAP-Rule:MF_01646}. 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; AE014075; AAN82582.1; -; Genomic_DNA. DR RefSeq; WP_000349860.1; NZ_CP051263.1. DR AlphaFoldDB; Q8FCW8; -. DR SMR; Q8FCW8; -. DR STRING; 199310.c4144; -. DR KEGG; ecc:c4144; -. DR eggNOG; COG0007; Bacteria. DR eggNOG; COG1648; Bacteria. DR HOGENOM; CLU_011276_2_0_6; -. DR BioCyc; ECOL199310:C4144-MONOMER; -. DR UniPathway; UPA00148; UER00211. DR UniPathway; UPA00148; UER00222. DR UniPathway; UPA00262; UER00211. DR UniPathway; UPA00262; UER00222. DR UniPathway; UPA00262; UER00376. DR Proteomes; UP000001410; Chromosome. DR GO; GO:0051287; F:NAD binding; IEA:InterPro. DR GO; GO:0043115; F:precorrin-2 dehydrogenase activity; IEA:UniProtKB-UniRule. DR GO; GO:0051266; F:sirohydrochlorin ferrochelatase activity; IEA:UniProtKB-EC. DR GO; GO:0004851; F:uroporphyrin-III C-methyltransferase activity; IEA:UniProtKB-UniRule. DR GO; GO:0009236; P:cobalamin biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0019354; P:siroheme biosynthetic process; IEA:UniProtKB-UniRule. DR CDD; cd11642; SUMT; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 1.10.8.210; Sirohaem synthase, dimerisation domain; 1. DR HAMAP; MF_01646; Siroheme_synth; 1. DR InterPro; IPR000878; 4pyrrol_Mease. DR InterPro; IPR035996; 4pyrrol_Methylase_sf. DR InterPro; IPR014777; 4pyrrole_Mease_sub1. DR InterPro; IPR014776; 4pyrrole_Mease_sub2. DR InterPro; IPR006366; CobA/CysG_C. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR037115; Sirohaem_synt_dimer_dom_sf. DR InterPro; IPR012409; Sirohaem_synth. DR InterPro; IPR028281; Sirohaem_synthase_central. DR InterPro; IPR019478; Sirohaem_synthase_dimer_dom. DR InterPro; IPR006367; Sirohaem_synthase_N. DR InterPro; IPR003043; Uropor_MeTrfase_CS. DR NCBIfam; TIGR01469; cobA_cysG_Cterm; 1. DR NCBIfam; TIGR01470; cysG_Nterm; 1. DR PANTHER; PTHR45790:SF1; SIROHEME SYNTHASE; 1. DR PANTHER; PTHR45790; SIROHEME SYNTHASE-RELATED; 1. DR Pfam; PF10414; CysG_dimeriser; 1. DR Pfam; PF13241; NAD_binding_7; 1. DR Pfam; PF14824; Sirohm_synth_M; 1. DR Pfam; PF00590; TP_methylase; 1. DR PIRSF; PIRSF036426; Sirohaem_synth; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR SUPFAM; SSF75615; Siroheme synthase middle domains-like; 1. DR SUPFAM; SSF53790; Tetrapyrrole methylase; 1. DR PROSITE; PS00839; SUMT_1; 1. DR PROSITE; PS00840; SUMT_2; 1. PE 3: Inferred from homology; KW Cobalamin biosynthesis; Lyase; Methyltransferase; Multifunctional enzyme; KW NAD; Oxidoreductase; Phosphoprotein; Porphyrin biosynthesis; KW Reference proteome; S-adenosyl-L-methionine; Transferase. FT CHAIN 1..457 FT /note="Siroheme synthase" FT /id="PRO_0000330510" FT REGION 1..204 FT /note="Precorrin-2 dehydrogenase /sirohydrochlorin FT ferrochelatase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT REGION 216..457 FT /note="Uroporphyrinogen-III C-methyltransferase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT ACT_SITE 248 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT ACT_SITE 270 FT /note="Proton donor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 22..23 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 43..44 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 225 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 301..303 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 306 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 331..332 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 382 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 411 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT MOD_RES 128 FT /note="Phosphoserine" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" SQ SEQUENCE 457 AA; 49977 MW; C76E0DC91D4DF2E5 CRC64; MDHLPIFCQL RDRDCLIVGG GDVAERKARL LLDAGARLTV NALAFIPQFT AWADAGMLTL VEGPFDESLL DTCWLAIAAT DDDALNQRVS EAAEARRIFC NVVDAPKAAS FIMPSIIDRS PLMVAVSSGG TSPVLARLLR EKLESLLPLH LGQVAKYAGQ LRGRVKQQFA TMGERRRFWE KLFVNDRLAQ SLANNDQKAI TETTEQLINE PLDHRGEVVL VGAGPGDAGL LTLKGLQQIQ QADVVVYDRL VSDDIMNLVR RDADRVFVGK RAGYHCVPQE EINQILLREA QKGKRVVRLK GGDPFIFGRG GEELETLCNA GIPFSVVPGI TAASGCSAYS GIPLTHRDYA QSVRLITGHL KTGGELDWEN LAAEKQTLVF YMGLNQAATI QQKLIEYGMP GEMPVAIVEN GTAVTQRVID GTLTQLGELA QQMNSPSLII IGRVVGLRDK LNWFSNH //