ID CYSG_ZYMMO Reviewed; 471 AA. AC Q5NRM4; DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-2005, sequence version 1. DT 27-MAR-2024, entry version 117. 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}; GN OrderedLocusNames=ZMO0006; OS Zymomonas mobilis subsp. mobilis (strain ATCC 31821 / ZM4 / CP4). OC Bacteria; Pseudomonadota; Alphaproteobacteria; Sphingomonadales; OC Zymomonadaceae; Zymomonas. OX NCBI_TaxID=264203; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 31821 / ZM4 / CP4; RX PubMed=15592456; DOI=10.1038/nbt1045; RA Seo J.-S., Chong H., Park H.S., Yoon K.-O., Jung C., Kim J.J., Hong J.H., RA Kim H., Kim J.-H., Kil J.-I., Park C.J., Oh H.-M., Lee J.-S., Jin S.-J., RA Um H.-W., Lee H.-J., Oh S.-J., Kim J.Y., Kang H.L., Lee S.Y., Lee K.J., RA Kang H.S.; RT "The genome sequence of the ethanologenic bacterium Zymomonas mobilis RT ZM4."; RL Nat. Biotechnol. 23:63-68(2005). 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; AE008692; AAV88630.1; -; Genomic_DNA. DR RefSeq; WP_011239994.1; NZ_CP035711.1. DR AlphaFoldDB; Q5NRM4; -. DR SMR; Q5NRM4; -. DR STRING; 264203.ZMO0006; -. DR KEGG; zmo:ZMO0006; -. DR eggNOG; COG0007; Bacteria. DR eggNOG; COG1648; Bacteria. DR HOGENOM; CLU_011276_2_0_5; -. DR UniPathway; UPA00148; UER00211. DR UniPathway; UPA00148; UER00222. DR UniPathway; UPA00262; UER00211. DR UniPathway; UPA00262; UER00222. DR UniPathway; UPA00262; UER00376. DR Proteomes; UP000001173; 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; 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; 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..471 FT /note="Siroheme synthase" FT /id="PRO_0000330582" FT REGION 1..203 FT /note="Precorrin-2 dehydrogenase /sirohydrochlorin FT ferrochelatase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT REGION 215..471 FT /note="Uroporphyrinogen-III C-methyltransferase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT ACT_SITE 247 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT ACT_SITE 269 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 224 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 300..302 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 305 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646" FT BINDING 330..331 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 471 AA; 51585 MW; 595FEA404D465F49 CRC64; MDYLPLFADI RQRPVLVVGG GEVAARKVAL LKKAGAIIKI VAKNIHPELQ ILQENHEIEW LAKSFSPEQL DHVFLVIAAT NDSLLNQQIY QAAEQRHRLV NVVDDQQKCS FIFPSIVDRA PITLALSSAG TSPVLVRMLR EKLEALLPQS LGKMAEIAGK WRPRIKEKLP AIKDRRLFWE KAFNGLFAHK VASGDWESAE KTLAEQLEKD NPKQGEIILV GAGPGDAGLL TLRGLQALQQ ADIVLYDYLV SPAVLEMIRR DAQKICVGKR AGHHSVAQEE TNRRLIEWAQ QGKKVVRLKG GDPFIFGRGG EELQAAKQAS IPFQVVPGIT AASGAAAYAG IPLTHRDYSQ NVVFITGHCQ KDGNGLDWAT LARPHQTLVI YMGVMNAGKI SEALIKHGRK ADTPVAIIAH ATLPNQQILN GRLDQLESLA KQAETPALLI IGEVGGLQSD LSWFSSKTDK EDTKSSLINL A //