ID   SUMT_SINSX              Reviewed;         280 AA.
AC   P21631;
DT   01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1991, sequence version 1.
DT   13-SEP-2023, entry version 105.
DE   RecName: Full=Uroporphyrinogen-III C-methyltransferase {ECO:0000305|PubMed:2546914};
DE            Short=Urogen III methylase;
DE            EC=2.1.1.107 {ECO:0000269|PubMed:2546914};
DE   AltName: Full=S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase {ECO:0000303|PubMed:2546914};
DE            Short=SUMT {ECO:0000303|PubMed:2546914};
DE   AltName: Full=Uroporphyrinogen III methylase;
DE            Short=UROM;
GN   Name=cobA {ECO:0000312|EMBL:AAA25773.1};
OS   Sinorhizobium sp.
OC   Bacteria; Pseudomonadota; Alphaproteobacteria; Hyphomicrobiales;
OC   Rhizobiaceae; Sinorhizobium/Ensifer group; Sinorhizobium.
OX   NCBI_TaxID=42445;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-10.
RC   STRAIN=SC510;
RX   PubMed=2211520; DOI=10.1128/jb.172.10.5968-5979.1990;
RA   Crouzet J., Cauchois L., Blanche F., Debussche L., Thibaut D.,
RA   Rouyez M.-C., Rigault S., Mayaux J.-F., Cameron B.;
RT   "Nucleotide sequence of a Pseudomonas denitrificans 5.4-kilobase DNA
RT   fragment containing five cob genes and identification of structural genes
RT   encoding S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase
RT   and cobyrinic acid a,c-diamide synthase.";
RL   J. Bacteriol. 172:5968-5979(1990).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP   SPECIFICITY, ACTIVITY REGULATION, SUBUNIT, DISRUPTION PHENOTYPE, AND
RP   PATHWAY.
RX   PubMed=2546914; DOI=10.1128/jb.171.8.4222-4231.1989;
RA   Blanche F., Debussche L., Thibaut D., Crouzet J., Cameron B.;
RT   "Purification and characterization of S-adenosyl-L-methionine:
RT   uroporphyrinogen III methyltransferase from Pseudomonas denitrificans.";
RL   J. Bacteriol. 171:4222-4231(1989).
RN   [3] {ECO:0007744|PDB:1S4D}
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH
RP   S-ADENOSYL-L-HOMOCYSTEINE, SUBUNIT, AND MUTAGENESIS OF ASP-47; LEU-49;
RP   PHE-106; THR-130; TYR-183 AND MET-184.
RX   PubMed=15522295; DOI=10.1016/j.jmb.2004.09.020;
RA   Vevodova J., Graham R.M., Raux E., Schubert H.L., Roper D.I.,
RA   Brindley A.A., Ian Scott A., Roessner C.A., Stamford N.P.J., Stroupe M.E.,
RA   Getzoff E.D., Warren M.J., Wilson K.S.;
RT   "Structure/function studies on a S-adenosyl-L-methionine-dependent
RT   uroporphyrinogen III C methyltransferase (SUMT), a key regulatory enzyme of
RT   tetrapyrrole biosynthesis.";
RL   J. Mol. Biol. 344:419-433(2004).
CC   -!- FUNCTION: Catalyzes the two successive C-2 and C-7 methylation
CC       reactions involved in the conversion of uroporphyrinogen III to
CC       precorrin-2 via the intermediate formation of precorrin-1. It is a step
CC       in the biosynthesis of both cobalamin (vitamin B12) and siroheme.
CC       Neither uroporphyrin III nor the chlorin (factor I) is a substrate of
CC       SUMT. {ECO:0000269|PubMed:2546914}.
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:0000269|PubMed:2546914};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32460;
CC         Evidence={ECO:0000305|PubMed:2546914};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-adenosyl-L-methionine + uroporphyrinogen III = H(+) +
CC         precorrin-1 + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:19089,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57308, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:58893, ChEBI:CHEBI:59789;
CC         Evidence={ECO:0000269|PubMed:2546914};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19090;
CC         Evidence={ECO:0000305|PubMed:2546914};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=precorrin-1 + S-adenosyl-L-methionine = precorrin-2 + S-
CC         adenosyl-L-homocysteine; Xref=Rhea:RHEA:21972, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:58827, ChEBI:CHEBI:58893, ChEBI:CHEBI:59789;
CC         Evidence={ECO:0000269|PubMed:2546914};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21973;
CC         Evidence={ECO:0000305|PubMed:2546914};
CC   -!- ACTIVITY REGULATION: S-adenosylhomocysteine is an extremely powerful
CC       competitive inhibitor of the uroporphyrinogen III methylation. SUMT
CC       exhibits a substrate inhibition phenomenon at uroporphyrinogen III
CC       concentrations above 2 uM; this property might play a regulatory role
CC       in cobalamin biosynthesis. The enzyme activity is completely
CC       insensitive to feedback inhibition by cobalamin and corrinoid
CC       intermediates. {ECO:0000269|PubMed:2546914}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=6.3 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:2546914};
CC         KM=1 uM for uroporphyrinogen III {ECO:0000269|PubMed:2546914};
CC         Vmax=640 nmol/h/mg enzyme {ECO:0000269|PubMed:2546914};
CC         Note=kcat is 38 h(-1). {ECO:0000269|PubMed:2546914};
CC       pH dependence:
CC         Optimum pH is 7.7. {ECO:0000269|PubMed:2546914};
CC   -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis;
CC       precorrin-2 from uroporphyrinogen III: step 1/1.
CC       {ECO:0000269|PubMed:2546914}.
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC       biosynthesis; precorrin-2 from uroporphyrinogen III: step 1/1.
CC       {ECO:0000305|PubMed:2546914}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15522295,
CC       ECO:0000269|PubMed:2546914}.
CC   -!- DISRUPTION PHENOTYPE: Cells lacking this gene are deficient in
CC       cobalamin biosynthesis. {ECO:0000269|PubMed:2546914}.
CC   -!- MISCELLANEOUS: Uroporphyrinogen III is a key intermediate because of
CC       its position at the branch point of two divergent pathways. One pathway
CC       leads to protoheme, and the other one is the cobalamin and siroheme
CC       pathway. {ECO:0000305|PubMed:2546914}.
CC   -!- SIMILARITY: Belongs to the precorrin methyltransferase family.
CC       {ECO:0000305}.
CC   -!- CAUTION: Was originally thought to originate from Pseudomonas
CC       denitrificans, but similarity searches show that the sequence is much
CC       closer to Sinorhizobium. The entry's taxonomy has been changed.
CC       {ECO:0000305}.
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DR   EMBL; M59236; AAA25773.1; -; Genomic_DNA.
DR   PDB; 1S4D; X-ray; 2.70 A; A/B/D/E/F/G/H/I/J/K/L/M=1-280.
DR   PDBsum; 1S4D; -.
DR   AlphaFoldDB; P21631; -.
DR   SMR; P21631; -.
DR   DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR   BioCyc; MetaCyc:MONOMER-82; -.
DR   UniPathway; UPA00148; UER00211.
DR   UniPathway; UPA00262; UER00211.
DR   EvolutionaryTrace; P21631; -.
DR   GO; GO:0004851; F:uroporphyrin-III C-methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0009236; P:cobalamin biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0019354; P:siroheme biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd11642; SUMT; 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; IPR003043; Uropor_MeTrfase_CS.
DR   NCBIfam; TIGR01469; cobA_cysG_Cterm; 1.
DR   PANTHER; PTHR45790:SF3; S-ADENOSYL-L-METHIONINE-DEPENDENT UROPORPHYRINOGEN III METHYLTRANSFERASE, CHLOROPLASTIC; 1.
DR   PANTHER; PTHR45790; SIROHEME SYNTHASE-RELATED; 1.
DR   Pfam; PF00590; TP_methylase; 1.
DR   SUPFAM; SSF53790; Tetrapyrrole methylase; 1.
DR   PROSITE; PS00839; SUMT_1; 1.
DR   PROSITE; PS00840; SUMT_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cobalamin biosynthesis; Direct protein sequencing;
KW   Methyltransferase; Porphyrin biosynthesis; S-adenosyl-L-methionine;
KW   Transferase.
FT   CHAIN           1..280
FT                   /note="Uroporphyrinogen-III C-methyltransferase"
FT                   /id="PRO_0000150372"
FT   BINDING         24
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000269|PubMed:15522295,
FT                   ECO:0007744|PDB:1S4D"
FT   BINDING         100..102
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000269|PubMed:15522295,
FT                   ECO:0007744|PDB:1S4D"
FT   BINDING         130..131
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000269|PubMed:15522295,
FT                   ECO:0007744|PDB:1S4D"
FT   BINDING         184
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000269|PubMed:15522295,
FT                   ECO:0007744|PDB:1S4D"
FT   BINDING         213
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000269|PubMed:15522295,
FT                   ECO:0007744|PDB:1S4D"
FT   BINDING         241
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000269|PubMed:15522295,
FT                   ECO:0007744|PDB:1S4D"
FT   MUTAGEN         47
FT                   /note="D->N: Reduces S-adenosyl-L-methionine binding by
FT                   about 75%. Causes accumulation of precorrin-1."
FT                   /evidence="ECO:0000269|PubMed:15522295"
FT   MUTAGEN         49
FT                   /note="L->A: Reduces S-adenosyl-L-methionine binding by
FT                   about 50%. Causes slow synthesis of precorrin-2 and
FT                   accumulation of precorrin-1."
FT                   /evidence="ECO:0000269|PubMed:15522295"
FT   MUTAGEN         106
FT                   /note="F->A: Strongly reduces S-adenosyl-L-methionine
FT                   binding. Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:15522295"
FT   MUTAGEN         130
FT                   /note="T->A: Strongly reduces S-adenosyl-L-methionine
FT                   binding. Causes slow synthesis of precorrin-2."
FT                   /evidence="ECO:0000269|PubMed:15522295"
FT   MUTAGEN         183
FT                   /note="Y->A: Strongly reduces S-adenosyl-L-methionine
FT                   binding. Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:15522295"
FT   MUTAGEN         184
FT                   /note="M->A: Strongly reduces S-adenosyl-L-methionine
FT                   binding. Causes drastic effects on enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:15522295"
FT   STRAND          17..21
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          23..25
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          29..31
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           32..40
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          42..46
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           54..57
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          64..66
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           78..90
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          95..101
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          105..108
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           109..117
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   TURN            118..120
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          123..126
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   TURN            131..133
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           134..138
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   TURN            146..148
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          150..156
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           170..174
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          178..184
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           189..198
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          206..212
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          219..224
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   TURN            225..227
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           228..235
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   STRAND          239..246
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           247..251
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           252..255
FT                   /evidence="ECO:0007829|PDB:1S4D"
FT   HELIX           257..261
FT                   /evidence="ECO:0007829|PDB:1S4D"
SQ   SEQUENCE   280 AA;  29253 MW;  3D593C535CF0610E CRC64;
     MIDDLFAGLP ALEKGSVWLV GAGPGDPGLL TLHAANALRQ ADVIVHDALV NEDCLKLARP
     GAVLEFAGKR GGKPSPKQRD ISLRLVELAR AGNRVLRLKG GDPFVFGRGG EEALTLVEHQ
     VPFRIVPGIT AGIGGLAYAG IPVTHREVNH AVTFLTGHDS SGLVPDRINW QGIASGSPVI
     VMYMAMKHIG AITANLIAGG RSPDEPVAFV CNAATPQQAV LETTLARAEA DVAAAGLEPP
     AIVVVGEVVR LRAALDWIGA LDGRKLAADP FANRILRNPA
//