ID   CYSG_NEIMA              Reviewed;         486 AA.
AC   P57001; A1IRZ2;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 1.
DT   27-MAR-2024, entry version 140.
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=NMA1367;
OS   Neisseria meningitidis serogroup A / serotype 4A (strain DSM 15465 /
OS   Z2491).
OC   Bacteria; Pseudomonadota; Betaproteobacteria; Neisseriales; Neisseriaceae;
OC   Neisseria.
OX   NCBI_TaxID=122587;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=DSM 15465 / Z2491;
RX   PubMed=10761919; DOI=10.1038/35006655;
RA   Parkhill J., Achtman M., James K.D., Bentley S.D., Churcher C.M.,
RA   Klee S.R., Morelli G., Basham D., Brown D., Chillingworth T., Davies R.M.,
RA   Davis P., Devlin K., Feltwell T., Hamlin N., Holroyd S., Jagels K.,
RA   Leather S., Moule S., Mungall K.L., Quail M.A., Rajandream M.A.,
RA   Rutherford K.M., Simmonds M., Skelton J., Whitehead S., Spratt B.G.,
RA   Barrell B.G.;
RT   "Complete DNA sequence of a serogroup A strain of Neisseria meningitidis
RT   Z2491.";
RL   Nature 404:502-506(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}.
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DR   EMBL; AL157959; CAM08540.1; -; Genomic_DNA.
DR   PIR; A81906; A81906.
DR   RefSeq; WP_002246198.1; NC_003116.1.
DR   AlphaFoldDB; P57001; -.
DR   SMR; P57001; -.
DR   EnsemblBacteria; CAM08540; CAM08540; NMA1367.
DR   KEGG; nma:NMA1367; -.
DR   HOGENOM; CLU_011276_2_0_4; -.
DR   UniPathway; UPA00148; UER00211.
DR   UniPathway; UPA00148; UER00222.
DR   UniPathway; UPA00262; UER00211.
DR   UniPathway; UPA00262; UER00222.
DR   UniPathway; UPA00262; UER00376.
DR   Proteomes; UP000000626; 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; 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   S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..486
FT                   /note="Siroheme synthase"
FT                   /id="PRO_0000150381"
FT   REGION          1..203
FT                   /note="Precorrin-2 dehydrogenase /sirohydrochlorin
FT                   ferrochelatase"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT   REGION          217..486
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"
SQ   SEQUENCE   486 AA;  52484 MW;  F70D6A5F50FF23CF 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 KRARGGRTPQ EDTNALMVRL AREGRRVVRL
     KGGDPFVFGR GGEELETLAR HQIPFSVVPG ITAAVGATAY AGIPLTHRDY AQSAVFVTGH
     RKADAPDIEW QTLARSRQTL VIYMGALKAA LIAERLQQHG RSPDTPAAVI SQGTLPAQKT
     ATGTLANLAE LAETAPNPAL IVIGEVVGLH EKLAWFGENA KKESNPAEHA YFALDGLGTG
     QEQQAA
//