ID   HEM4_RUMJO              Reviewed;         504 AA.
AC   Q59294;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   25-MAY-2022, entry version 98.
DE   RecName: Full=Porphyrin biosynthesis protein HemD;
DE   Includes:
DE     RecName: Full=Uroporphyrinogen-III C-methyltransferase;
DE              Short=Urogen III methylase;
DE              EC=2.1.1.107;
DE     AltName: Full=SUMT;
DE     AltName: Full=Uroporphyrinogen III methylase;
DE              Short=UROM;
DE   Includes:
DE     RecName: Full=Uroporphyrinogen-III synthase;
DE              Short=UROS;
DE              EC=4.2.1.75;
DE     AltName: Full=Hydroxymethylbilane hydrolyase [cyclizing];
DE     AltName: Full=Uroporphyrinogen-III cosynthase;
GN   Name=hemD;
OS   Ruminiclostridium josui (Clostridium josui).
OC   Bacteria; Firmicutes; Clostridia; Eubacteriales; Oscillospiraceae;
OC   Ruminiclostridium.
OX   NCBI_TaxID=1499;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC   STRAIN=DSM 25723 / FERM P-9684 / JCM 17888 / KCTC 15379 / III;
RX   PubMed=7665501; DOI=10.1128/jb.177.17.5169-5175.1995;
RA   Fujino E., Fujino T., Karita S., Sakka K., Ohmiya K.;
RT   "Cloning and sequencing of some genes responsible for porphyrin
RT   biosynthesis from the anaerobic bacterium Clostridium josui.";
RL   J. Bacteriol. 177:5169-5175(1995).
CC   -!- FUNCTION: May catalyze sequential reactions to synthesize
CC       uroporphyrinogen III from hydroxymethylbilane (HMB) and then precorrin-
CC       2, which are intermediate compounds in both vitamin B12 and siroheme
CC       biosyntheses. {ECO:0000305|PubMed:7665501}.
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=hydroxymethylbilane = H2O + uroporphyrinogen III;
CC         Xref=Rhea:RHEA:18965, ChEBI:CHEBI:15377, ChEBI:CHEBI:57308,
CC         ChEBI:CHEBI:57845; EC=4.2.1.75;
CC   -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis;
CC       precorrin-2 from uroporphyrinogen III: step 1/1.
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC       biosynthesis; precorrin-2 from uroporphyrinogen III: step 1/1.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the precorrin
CC       methyltransferase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the uroporphyrinogen-
CC       III synthase family. {ECO:0000305}.
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DR   EMBL; D28503; BAA05862.1; -; Genomic_DNA.
DR   PIR; I40811; I40811.
DR   AlphaFoldDB; Q59294; -.
DR   SMR; Q59294; -.
DR   UniPathway; UPA00148; UER00211.
DR   UniPathway; UPA00262; UER00211.
DR   GO; GO:0004851; F:uroporphyrin-III C-methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004852; F:uroporphyrinogen-III synthase 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; cd06578; HemD; 1.
DR   CDD; cd11642; SUMT; 1.
DR   Gene3D; 3.30.950.10; -; 1.
DR   Gene3D; 3.40.1010.10; -; 1.
DR   Gene3D; 3.40.50.10090; -; 2.
DR   InterPro; IPR000878; 4pyrrol_Mease.
DR   InterPro; IPR035996; 4pyrrol_Methylase_sf.
DR   InterPro; IPR036108; 4pyrrol_syn_uPrphyn_synt_sf.
DR   InterPro; IPR003754; 4pyrrol_synth_uPrphyn_synth.
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   Pfam; PF02602; HEM4; 1.
DR   Pfam; PF00590; TP_methylase; 1.
DR   SUPFAM; SSF53790; SSF53790; 1.
DR   SUPFAM; SSF69618; SSF69618; 1.
DR   TIGRFAMs; TIGR01469; cobA_cysG_Cterm; 1.
DR   PROSITE; PS00839; SUMT_1; 1.
DR   PROSITE; PS00840; SUMT_2; 1.
PE   3: Inferred from homology;
KW   Lyase; Methyltransferase; Multifunctional enzyme; Porphyrin biosynthesis;
KW   S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..504
FT                   /note="Porphyrin biosynthesis protein HemD"
FT                   /id="PRO_0000150383"
FT   REGION          1..248
FT                   /note="Uroporphyrinogen-III C-methyltransferase"
FT   REGION          249..504
FT                   /note="Uroporphyrinogen-III synthase"
SQ   SEQUENCE   504 AA;  55211 MW;  86FB0DACEFD641D7 CRC64;
     MEHGFVALVG AGPGDKGLIT IRGAELLSQA DVVVYDRLVS QEIIKMIPTT AEKIDVGKEN
     KFHPVKQEEI NHILLEKSLE GKKVIRLKGG DPFVFGRGGE ELELLYENNI PFEVVPGVTS
     AVAALCYGGI PATHRDFCSS LHIITGHARE GGQLSIPFHE LKELNGTIVF LMGDSSLSYL
     MNGLINAGME KDMPAAIVEN GTRPNQRKLV ATVGTLEQKA LEMEIKSPAI IAVGKVCSLS
     EKFSWFMKKP LFGTKILVTR PKESSGTLVE KLRQLGAEPV EYPCIEVVPI PQNEKLYHAC
     ENIREYGWIL LTSKNGIQIF FDYLNSKGLD ARVLANTKIG TVGSQTAKAL KEVGLISDFT
     PEIFDGRHLA LGIAERVGEN EKVLICDAAI ASDDIVNILR SNNIKFDRVP LYNTNYINEN
     SNKVKKSIVH GELKYITFTS ASTVEGFIAS MKDIPLESLT AVCIGNKTAE AAKKYNLRYV
     VAEKSTIDSM IDKLLEIGGG NIYD