ID CYSG_NEIMB Reviewed; 483 AA. AC P95370; Q9JQK6; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 3. DT 27-MAR-2024, entry version 157. 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}; Synonyms=cysG1; GN OrderedLocusNames=NMB1156; GN and GN Name=cysG2 {ECO:0000255|HAMAP-Rule:MF_01646}; GN OrderedLocusNames=NMB1194; OS Neisseria meningitidis serogroup B (strain MC58). OC Bacteria; Pseudomonadota; Betaproteobacteria; Neisseriales; Neisseriaceae; OC Neisseria. OX NCBI_TaxID=122586; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=MC58; RA McVeigh T., Wilkie S.E., Woodcock S.C., Mortuza G., Peters S.E., RA Warren M.J.; RT "Sirohaem synthase from Neisseria meningitidis."; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=MC58; RX PubMed=10710307; DOI=10.1126/science.287.5459.1809; RA Tettelin H., Saunders N.J., Heidelberg J.F., Jeffries A.C., Nelson K.E., RA Eisen J.A., Ketchum K.A., Hood D.W., Peden J.F., Dodson R.J., Nelson W.C., RA Gwinn M.L., DeBoy R.T., Peterson J.D., Hickey E.K., Haft D.H., RA Salzberg S.L., White O., Fleischmann R.D., Dougherty B.A., Mason T.M., RA Ciecko A., Parksey D.S., Blair E., Cittone H., Clark E.B., Cotton M.D., RA Utterback T.R., Khouri H.M., Qin H., Vamathevan J.J., Gill J., Scarlato V., RA Masignani V., Pizza M., Grandi G., Sun L., Smith H.O., Fraser C.M., RA Moxon E.R., Rappuoli R., Venter J.C.; RT "Complete genome sequence of Neisseria meningitidis serogroup B strain RT MC58."; RL Science 287:1809-1815(2000). 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; Y10177; CAA71251.1; -; Genomic_DNA. DR EMBL; AE002098; AAF41542.1; -; Genomic_DNA. DR EMBL; AE002098; AAF41577.1; -; Genomic_DNA. DR PIR; D81111; D81111. DR PIR; T46867; T46867. DR RefSeq; NP_274184.1; NC_003112.2. DR RefSeq; NP_274220.1; NC_003112.2. DR RefSeq; WP_002225211.1; NC_003112.2. DR AlphaFoldDB; P95370; -. DR SMR; P95370; -. DR STRING; 122586.NMB1156; -. DR PaxDb; 122586-NMB1156; -. DR KEGG; nme:NMB1156; -. DR KEGG; nme:NMB1194; -. DR PATRIC; fig|122586.8.peg.1461; -. DR HOGENOM; CLU_011276_2_0_4; -. DR InParanoid; P95370; -. DR OrthoDB; 9815856at2; -. DR UniPathway; UPA00148; UER00211. DR UniPathway; UPA00148; UER00222. DR UniPathway; UPA00262; UER00211. DR UniPathway; UPA00262; UER00222. DR UniPathway; UPA00262; UER00376. DR Proteomes; UP000000425; Chromosome. DR GO; GO:0051287; F:NAD binding; IEA:InterPro. DR GO; GO:0043115; F:precorrin-2 dehydrogenase activity; IBA:GO_Central. 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; IBA:GO_Central. 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; IPR028161; Met8-like. 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; PTHR35330; SIROHEME BIOSYNTHESIS PROTEIN MET8; 1. DR PANTHER; PTHR35330:SF1; SIROHEME BIOSYNTHESIS PROTEIN MET8; 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..483 FT /note="Siroheme synthase" FT /id="PRO_0000150382" FT REGION 1..203 FT /note="Precorrin-2 dehydrogenase /sirohydrochlorin FT ferrochelatase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT REGION 217..483 FT /note="Uroporphyrinogen-III C-methyltransferase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT ACT_SITE 249 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT ACT_SITE 271 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 226 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 302..304 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 307 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 332..333 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 384 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 413 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" FT CONFLICT 475..483 FT /note="GLNAGQRAA -> D (in Ref. 1; CAA71251)" FT /evidence="ECO:0000305" SQ SEQUENCE 483 AA; 52111 MW; 279C4F458B19582F CRC64; MNYFPIFANL AGRPVLVVGG GAVAARKISL LLKAGAEVRV AAKHLNAELS ALAAENKILW LAEEFRAEHI RTVFLIIAAS SDQALNRRVF HLAESCQKPV NVVDDRDHCS FIFPSVIDRN PVQIAVSSSG SAPVLARLLR ERLEALLPPS LGDMAEISGR WRDAVKGKLK SVTERRRFWE KQFNGRFAAL VKNRQNTLAE RELAGQLEQS RQNDQGGSVS LVGAGPGDAG LLTLKGLQEI QQADVVLYDA LVSDGILSLV RRDAERIFVG KRARGERTPQ EDTNALMVRL AREGRRVVRL KGGDPFVFGR GGEELETLAR HQIPFSVVPG ITAAVGATAY AGIPLTHRDY AQSAVFVTGH RKADAPDIEW QTLARSRQTL VIYMGALKAA LIAERLQQHG RSPDTPAAVI SQGTLPAQKT ATGTLANLAE LAETAPNPAL IVIGEVVGLH EKLAWFGENG EGENRVGQTY PALGGLNAGQ RAA //