ID   CYSG_SALA4              Reviewed;         459 AA.
AC   B5F8J0;
DT   28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT   14-OCT-2008, sequence version 1.
DT   27-MAR-2024, entry version 84.
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=SeAg_B3675;
OS   Salmonella agona (strain SL483).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Salmonella.
OX   NCBI_TaxID=454166;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=SL483;
RX   PubMed=21602358; DOI=10.1128/jb.00297-11;
RA   Fricke W.F., Mammel M.K., McDermott P.F., Tartera C., White D.G.,
RA   Leclerc J.E., Ravel J., Cebula T.A.;
RT   "Comparative genomics of 28 Salmonella enterica isolates: evidence for
RT   CRISPR-mediated adaptive sublineage evolution.";
RL   J. Bacteriol. 193:3556-3568(2011).
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}.
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DR   EMBL; CP001138; ACH52886.1; -; Genomic_DNA.
DR   RefSeq; WP_000349898.1; NC_011149.1.
DR   AlphaFoldDB; B5F8J0; -.
DR   SMR; B5F8J0; -.
DR   KEGG; sea:SeAg_B3675; -.
DR   HOGENOM; CLU_011276_2_1_6; -.
DR   UniPathway; UPA00148; UER00211.
DR   UniPathway; UPA00148; UER00222.
DR   UniPathway; UPA00262; UER00211.
DR   UniPathway; UPA00262; UER00222.
DR   UniPathway; UPA00262; UER00376.
DR   Proteomes; UP000008819; 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   S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..459
FT                   /note="Siroheme synthase"
FT                   /id="PRO_1000186950"
FT   REGION          1..204
FT                   /note="Precorrin-2 dehydrogenase /sirohydrochlorin
FT                   ferrochelatase"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT   REGION          216..459
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   459 AA;  50437 MW;  66B7EF2C8CA8D578 CRC64;
     MDHLPIFCQL RDRDCLIVGG GDVAERKARL LLEAGARLTV NALTFIPQFT VWANEGMLTL
     VEGPFDETLL DSCWLAIAAT DDDTVNQRVS DAAESRRIFC NVVDAPKAAS FIMPSIIDRS
     PLMVAVSSGG TSPVLARLLR EKLESLLPQH LGQVARYAGQ LRARVKKQFA TMGERRRFWE
     KFFVNDRLAQ SLANADEKAV NATTERLFSE PLDHRGEVVL VGAGPGDAGL LTLKGLQQIQ
     QADIVVYDRL VSDDIMNLVR RDADRVFVGK RAGYHCVPQE EINQILLREA QKGKRVVRLK
     GGDPFIFGRG GEELETLCHA GIPFSVVPGI TAASGCSAYS GIPLTHRDYA QSVRLVTGHL
     KTGGELDWEN LAAEKQTLVF YMGLNQAATI QEKLIAFGMQ ADMPVALVEN GTSVKQRVVH
     GVLTQLGELA QQVESPALII VGRVVGLRDK LNWFSNYYD
//