CYSG_ECOLI
ID CYSG_ECOLI Reviewed; 457 AA.
AC P0AEA8; P11098; P76685; Q2M734;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Siroheme synthase {ECO:0000255|HAMAP-Rule:MF_01646, ECO:0000303|PubMed:8243665};
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, ECO:0000269|PubMed:2407234, ECO:0000269|PubMed:8573073, ECO:0000269|PubMed:9461500};
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, ECO:0000269|PubMed:8243665, ECO:0000269|PubMed:9461500};
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, ECO:0000269|PubMed:8243665, ECO:0000269|PubMed:9461500};
GN Name=cysG {ECO:0000255|HAMAP-Rule:MF_01646};
GN OrderedLocusNames=b3368, JW3331;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=2543955; DOI=10.1093/nar/17.10.3865;
RA Bell A.I., Gaston K.L., Cole J.A., Busby S.J.W.;
RT "Cloning of binding sequences for the Escherichia coli transcription
RT activators, FNR and CRP: location of bases involved in discrimination
RT between FNR and CRP.";
RL Nucleic Acids Res. 17:3865-3874(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=2200672; DOI=10.1111/j.1432-1033.1990.tb19125.x;
RA Peakman T., Crouzet J., Mayaux J.F., Busby S.J.W., Mohan S., Harborne N.,
RA Wootton J., Nicolson R., Cole J.A.;
RT "Nucleotide sequence, organisation and structural analysis of the products
RT of genes in the nirB-cysG region of the Escherichia coli K-12 chromosome.";
RL Eur. J. Biochem. 191:315-323(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP PROTEIN SEQUENCE OF 1-18, AND FUNCTION.
RX PubMed=2407558; DOI=10.1016/0014-5793(90)80640-5;
RA Warren M.J., Stolowich N.J., Santander P.J., Roessner C.A., Sowa B.A.,
RA Scott A.I.;
RT "Enzymatic synthesis of dihydrosirohydrochlorin (precorrin-2) and of a
RT novel pyrrocorphin by uroporphyrinogen III methylase.";
RL FEBS Lett. 261:76-80(1990).
RN [6]
RP FUNCTION AS A METHYLTRANSFERASE, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=2407234; DOI=10.1042/bj2650725;
RA Warren M.J., Roessner C.A., Santander P.J., Scott A.I.;
RT "The Escherichia coli cysG gene encodes S-adenosylmethionine-dependent
RT uroporphyrinogen III methylase.";
RL Biochem. J. 265:725-729(1990).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8243665; DOI=10.1016/0014-5793(93)80438-z;
RA Spencer J.B., Stolowich N.J., Roessner C.A., Scott A.I.;
RT "The Escherichia coli cysG gene encodes the multifunctional protein,
RT siroheme synthase.";
RL FEBS Lett. 335:57-60(1993).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8573073; DOI=10.1042/bj3130415;
RA Woodcock S.C., Warren M.J.;
RT "Evidence for a covalent intermediate in the S-adenosyl-L-methionine-
RT dependent transmethylation reaction catalysed by sirohaem synthase.";
RL Biochem. J. 313:415-421(1996).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLY-21; GLY-224; ASP-227;
RP LYS-270; ARG-298; ASP-303 AND ARG-309.
RX PubMed=9461500; DOI=10.1042/bj3300121;
RA Woodcock S.C., Raux E., Levillayer F., Thermes C., Rambach A., Warren M.J.;
RT "Effect of mutations in the transmethylase and dehydrogenase/chelatase
RT domains of sirohaem synthase (CysG) on sirohaem and cobalamin
RT biosynthesis.";
RL Biochem. J. 330:121-129(1998).
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, ECO:0000269|PubMed:2407234,
CC ECO:0000269|PubMed:2407558, ECO:0000269|PubMed:8243665,
CC ECO:0000269|PubMed:8573073, ECO:0000269|PubMed:9461500}.
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 ECO:0000269|PubMed:2407234, ECO:0000269|PubMed:8573073,
CC ECO:0000269|PubMed:9461500};
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 ECO:0000269|PubMed:8243665, ECO:0000269|PubMed:9461500};
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 ECO:0000269|PubMed:8243665, ECO:0000269|PubMed:9461500};
CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis;
CC precorrin-2 from uroporphyrinogen III: step 1/1. {ECO:0000255|HAMAP-
CC Rule:MF_01646, ECO:0000305|PubMed:2407234}.
CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis;
CC sirohydrochlorin from precorrin-2: step 1/1. {ECO:0000255|HAMAP-
CC Rule:MF_01646, ECO:0000305|PubMed:8243665}.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; precorrin-2 from uroporphyrinogen III: step 1/1.
CC {ECO:0000255|HAMAP-Rule:MF_01646, ECO:0000305|PubMed:2407234}.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; siroheme from sirohydrochlorin: step 1/1.
CC {ECO:0000255|HAMAP-Rule:MF_01646, ECO:0000305|PubMed:8243665}.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; sirohydrochlorin from precorrin-2: step 1/1.
CC {ECO:0000255|HAMAP-Rule:MF_01646, ECO:0000305|PubMed:8243665}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:2407234}.
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; X14202; CAA32419.1; -; Genomic_DNA.
DR EMBL; U18997; AAA58165.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76393.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77922.1; -; Genomic_DNA.
DR PIR; C65131; C65131.
DR RefSeq; NP_417827.1; NC_000913.3.
DR RefSeq; WP_000349855.1; NZ_STEB01000004.1.
DR AlphaFoldDB; P0AEA8; -.
DR SMR; P0AEA8; -.
DR BioGRID; 4262478; 6.
DR IntAct; P0AEA8; 1.
DR STRING; 511145.b3368; -.
DR jPOST; P0AEA8; -.
DR PaxDb; P0AEA8; -.
DR PRIDE; P0AEA8; -.
DR EnsemblBacteria; AAC76393; AAC76393; b3368.
DR EnsemblBacteria; BAE77922; BAE77922; BAE77922.
DR GeneID; 66672751; -.
DR GeneID; 947880; -.
DR KEGG; ecj:JW3331; -.
DR KEGG; eco:b3368; -.
DR PATRIC; fig|1411691.4.peg.3361; -.
DR EchoBASE; EB0185; -.
DR eggNOG; COG0007; Bacteria.
DR eggNOG; COG1648; Bacteria.
DR HOGENOM; CLU_011276_2_0_6; -.
DR InParanoid; P0AEA8; -.
DR OMA; GRFMAQE; -.
DR PhylomeDB; P0AEA8; -.
DR BioCyc; EcoCyc:SIROHEMESYN-MON; -.
DR BioCyc; MetaCyc:SIROHEMESYN-MON; -.
DR UniPathway; UPA00148; UER00211.
DR UniPathway; UPA00148; UER00222.
DR UniPathway; UPA00262; UER00211.
DR UniPathway; UPA00262; UER00222.
DR UniPathway; UPA00262; UER00376.
DR PRO; PR:P0AEA8; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; 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; IDA:EcoCyc.
DR GO; GO:0009236; P:cobalamin biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006970; P:response to osmotic stress; IMP:EcoCyc.
DR GO; GO:0019354; P:siroheme biosynthetic process; IBA:GO_Central.
DR CDD; cd11642; SUMT; 1.
DR Gene3D; 1.10.8.210; -; 1.
DR Gene3D; 3.30.950.10; -; 1.
DR Gene3D; 3.40.1010.10; -; 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 Pfam; PF10414; CysG_dimeriser; 1.
DR Pfam; PF14824; Sirohm_synth_M; 1.
DR Pfam; PF00590; TP_methylase; 1.
DR PIRSF; PIRSF036426; Sirohaem_synth; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53790; SSF53790; 1.
DR TIGRFAMs; TIGR01469; cobA_cysG_Cterm; 1.
DR TIGRFAMs; TIGR01470; cysG_Nterm; 1.
DR PROSITE; PS00839; SUMT_1; 1.
DR PROSITE; PS00840; SUMT_2; 1.
PE 1: Evidence at protein level;
KW Cobalamin biosynthesis; Direct protein sequencing; Lyase;
KW Methyltransferase; Multifunctional enzyme; NAD; Oxidoreductase;
KW Phosphoprotein; Porphyrin biosynthesis; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..457
FT /note="Siroheme synthase"
FT /id="PRO_0000150378"
FT REGION 4..204
FT /note="Precorrin-2 dehydrogenase /sirohydrochlorin
FT ferrochelatase"
FT /evidence="ECO:0000250"
FT REGION 216..448
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"
FT MUTAGEN 21
FT /note="G->D: It has methyltransferase and ferrochelatase
FT activities but a greatly reduced dehydrogenase activity. It
FT is able to bind AdoMet."
FT /evidence="ECO:0000269|PubMed:9461500"
FT MUTAGEN 224
FT /note="G->A: It abolishes methyltransferase activity, but
FT has dehydrogenase and ferrochelatase activities. It is
FT unable to bind AdoMet."
FT /evidence="ECO:0000269|PubMed:9461500"
FT MUTAGEN 227
FT /note="D->A: It has all activities of CysG."
FT /evidence="ECO:0000269|PubMed:9461500"
FT MUTAGEN 248
FT /note="D->A: It abolishes methyltransferase activity, but
FT has dehydrogenase and ferrochelatase activities. It is able
FT to bind AdoMet."
FT MUTAGEN 270
FT /note="K->I: It has all activities of CysG. It is able to
FT bind AdoMet."
FT /evidence="ECO:0000269|PubMed:9461500"
FT MUTAGEN 298
FT /note="R->L: It abolishes methyltransferase activity, but
FT has dehydrogenase and ferrochelatase activities. It is
FT unable to bind AdoMet."
FT /evidence="ECO:0000269|PubMed:9461500"
FT MUTAGEN 303
FT /note="D->A: It has all activities of CysG. It is able to
FT bind AdoMet."
FT /evidence="ECO:0000269|PubMed:9461500"
FT MUTAGEN 309
FT /note="R->L: It abolishes methyltransferase activity, but
FT has dehydrogenase and ferrochelatase activities. It is able
FT to bind AdoMet."
FT /evidence="ECO:0000269|PubMed:9461500"
FT CONFLICT 26
FT /note="R -> P (in Ref. 1; CAA32419 and 2; AAA58165)"
FT /evidence="ECO:0000305"
FT CONFLICT 90..91
FT /note="SE -> RQ (in Ref. 1; CAA32419 and 2; AAA58165)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 457 AA; 49951 MW; DDDE0DC90C5CF2F4 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 QQKLIEHGMP GEMPVAIVEN GTAVTQRVID
GTLTQLGELA QQMNSPSLII IGRVVGLRDK LNWFSNH
