ID   HEM4_PSEAE              Reviewed;         251 AA.
AC   P48246;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   08-DEC-2000, sequence version 2.
DT   04-NOV-2026, entry version 131.
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; OrderedLocusNames=PA5259;
OS   Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS   14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC   Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC   Pseudomonadales; Pseudomonadaceae; Pseudomonas.
OX   NCBI_TaxID=208964;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8159168; DOI=10.1007/bf00391011;
RA   Mohr C.D., Sonsteby S.K., Deretic V.;
RT   "The Pseudomonas aeruginosa homologs of hemC and hemD are linked to the
RT   gene encoding the regulator of mucoidy AlgR.";
RL   Mol. Gen. Genet. 242:177-184(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 /
RC   1C / PRS 101 / PAO1;
RX   PubMed=10984043; DOI=10.1038/35023079;
RA   Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA   Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA   Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA   Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA   Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA   Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT   "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT   pathogen.";
RL   Nature 406:959-964(2000).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY OF APOPROTEIN, AND SUBUNIT.
RX   PubMed=23295481; DOI=10.1107/s1744309112044739;
RA   Moynie L., Schnell R., McMahon S.A., Sandalova T., Boulkerou W.A.,
RA   Schmidberger J.W., Alphey M., Cukier C., Duthie F., Kopec J., Liu H.,
RA   Jacewicz A., Hunter W.N., Naismith J.H., Schneider G.;
RT   "The AEROPATH project targeting Pseudomonas aeruginosa: crystallographic
RT   studies for assessment of potential targets in early-stage drug
RT   discovery.";
RL   Acta Crystallogr. F 69:25-34(2013).
CC   -!- FUNCTION: Catalyzes cyclization of the linear tetrapyrrole,
CC       hydroxymethylbilane, to the macrocyclic uroporphyrinogen III.
CC       {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=hydroxymethylbilane = uroporphyrinogen III + H2O;
CC         Xref=Rhea:RHEA:18965, ChEBI:CHEBI:15377, ChEBI:CHEBI:57308,
CC         ChEBI:CHEBI:57845; EC=4.2.1.75;
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC       biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 3/4.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23295481}.
CC   -!- SIMILARITY: Belongs to the uroporphyrinogen-III synthase family.
CC       {ECO:0000305}.
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DR   EMBL; M74844; AAA18908.1; -; Genomic_DNA.
DR   EMBL; AE004091; AAG08644.1; -; Genomic_DNA.
DR   PIR; A82989; A82989.
DR   PIR; S41587; S41587.
DR   RefSeq; NP_253946.1; NC_002516.2.
DR   RefSeq; WP_003114032.1; NC_002516.2.
DR   PDB; 4ES6; X-ray; 2.22 A; A=1-251.
DR   PDB; 6TH8; NMR; -; A=130-251.
DR   BMRB; P48246; -.
DR   SMR; P48246; -.
DR   STRING; 208964.PA5259; -.
DR   PaxDb; 208964-PA5259; -.
DR   DNASU; 879724; -.
DR   GeneID; 879724; -.
DR   KEGG; pae:PA5259; -.
DR   PATRIC; fig|208964.12.peg.5512; -.
DR   PseudoCAP; PA5259; -.
DR   HOGENOM; CLU_011276_9_4_6; -.
DR   InParanoid; P48246; -.
DR   OMA; AACHQSV; -.
DR   OrthoDB; 9787650at2; -.
DR   PhylomeDB; P48246; -.
DR   BioCyc; PAER208964:G1FZ6-5380-MONOMER; -.
DR   UniPathway; UPA00251; UER00320.
DR   EvolutionaryTrace; P48246; -.
DR   CDD; cd06578; HemD; 1.
DR   Gene3D; 3.40.50.10090; -; 2.
DR   InterPro; IPR036108; 4pyrrol_syn_uPrphyn_synt_sf.
DR   InterPro; IPR003754; 4pyrrol_synth_uPrphyn_synth.
DR   InterPro; IPR039793; UROS/Hem4.
DR   PANTHER; PTHR38042; UROPORPHYRINOGEN-III SYNTHASE, CHLOROPLASTIC; 1.
DR   PANTHER; PTHR38042:SF1; UROPORPHYRINOGEN-III SYNTHASE, CHLOROPLASTIC; 1.
DR   Pfam; PF02602; HEM4; 1.
DR   SUPFAM; SSF69618; HemD-like; 1.
DR   NCBIfam; NF004395; PRK05752.1; 1.
DR   GO; GO:0004852; F:uroporphyrinogen-III synthase activity; ISS:PseudoCAP.
DR   GO; GO:0006780; P:uroporphyrinogen III biosynthetic process; IEA:InterPro.
DR   Proteomes; UP000002438; Chromosome.
DR   AlphaFoldDB; P48246; -.
DR   FunCoup; P48246; 169.
PE   1: Evidence at protein level;
KW   3D-structure; Lyase; Porphyrin biosynthesis; Reference proteome.
FT   CHAIN           1..251
FT                   /note="Uroporphyrinogen-III synthase"
FT                   /id="PRO_0000135245"
FT   CONFLICT        195..203
FT                   /note="QNLYQLAAA -> PKSVSVGGS (in Ref. 1; AAA18908)"
FT                   /evidence="ECO:0000305"
FT   STRAND          5..8
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           12..24
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          28..31
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          36..39
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           40..43
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           44..51
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           53..55
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          57..61
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           64..77
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          85..90
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           91..100
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           113..117
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           120..125
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          128..130
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          132..137
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           144..151
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          155..160
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          162..165
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           173..180
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          185..187
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           191..201
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           202..204
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           205..208
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          213..217
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           218..226
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          230..234
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   STRAND          236..239
FT                   /evidence="ECO:0007829|PDB:4ES6"
FT   HELIX           240..249
FT                   /evidence="ECO:0007829|PDB:4ES6"
SQ   SEQUENCE   251 AA;  27279 MW;  EEF61A160175264A CRC64;
     MSGWRLLLTR PDEECAALAA SLGEAGVHSS SLPLLAIDPL EETPEQRTLM LDLDRYCAVV
     VVSKPAARLG LERLDRYWPQ PPQQTWCSVG AATAAILEAY GLDVTYPEQG DDSEALLALP
     AFQDSLRVHD PKVLIMRGEG GREFLAERLR GQGVQVDYLP LYRRRAPDYP AGELLARVRA
     ERLNGLVVSS GQGLQNLYQL AAADWPEIGR LPLFVPSPRV AEMARELGAQ RVIDCRGASA
     PALLAALTSA A
//