ID   HGD_CAEEL               Reviewed;         437 AA.
AC   Q9Y041; O62087; Q9NJP3;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   27-APR-2001, sequence version 2.
DT   27-MAR-2024, entry version 160.
DE   RecName: Full=Homogentisate 1,2-dioxygenase;
DE            EC=1.13.11.5;
DE   AltName: Full=Homogentisate oxygenase;
DE   AltName: Full=Homogentisic acid oxidase;
DE   AltName: Full=Homogentisicase;
GN   Name=hgo-1 {ECO:0000312|WormBase:W06D4.1};
GN   ORFNames=W06D4.1 {ECO:0000312|WormBase:W06D4.1};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Bristol N2;
RA   Schmidt S.R., Werner E., Mueller C.R., Kress W.;
RT   "Cloning and characterization of the homogentisate 1,2-dioxygenase gene in
RT   A. thaliana and C. elegans.";
RL   Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Bristol N2; TISSUE=Embryo;
RA   Schmidt S.R., Werner E., Mueller C.R., Kress W.;
RT   "Sequence homology of HGO genes in eukaryotic organisms.";
RL   Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2;
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [4]
RP   FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP   GLY-173.
RX   PubMed=18227072; DOI=10.1074/jbc.m708341200;
RA   Fisher A.L., Page K.E., Lithgow G.J., Nash L.;
RT   "The Caenorhabditis elegans K10C2.4 gene encodes a member of the
RT   fumarylacetoacetate hydrolase family: a Caenorhabditis elegans model of
RT   type I tyrosinemia.";
RL   J. Biol. Chem. 283:9127-9135(2008).
CC   -!- FUNCTION: Plays a role in the tyrosine degradation pathway.
CC       {ECO:0000305|PubMed:18227072}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=homogentisate + O2 = 4-maleylacetoacetate + H(+);
CC         Xref=Rhea:RHEA:15449, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:16169, ChEBI:CHEBI:17105; EC=1.13.11.5;
CC   -!- COFACTOR:
CC       Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC   -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC       acetoacetate and fumarate from L-phenylalanine: step 4/6.
CC   -!- TISSUE SPECIFICITY: Expressed in the hypodermis and intestine.
CC       {ECO:0000269|PubMed:18227072}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown together with fah-1 RNAi
CC       rescues the impaired growth and fertility defects in the single fah-1
CC       RNAi mutant. {ECO:0000269|PubMed:18227072}.
CC   -!- SIMILARITY: Belongs to the homogentisate dioxygenase family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF136150; AAF61419.1; -; Genomic_DNA.
DR   EMBL; U95181; AAD00776.1; -; mRNA.
DR   EMBL; BX284601; CAA22255.4; -; Genomic_DNA.
DR   EMBL; Z93778; CAA22255.4; JOINED; Genomic_DNA.
DR   PIR; T19626; T19626.
DR   PIR; T37469; T37469.
DR   RefSeq; NP_492433.1; NM_060032.6.
DR   AlphaFoldDB; Q9Y041; -.
DR   SMR; Q9Y041; -.
DR   BioGRID; 38158; 6.
DR   STRING; 6239.W06D4.1.1; -.
DR   iPTMnet; Q9Y041; -.
DR   EPD; Q9Y041; -.
DR   PaxDb; 6239-W06D4-1; -.
DR   PeptideAtlas; Q9Y041; -.
DR   EnsemblMetazoa; W06D4.1.1; W06D4.1.1; WBGene00001843.
DR   GeneID; 172726; -.
DR   KEGG; cel:CELE_W06D4.1; -.
DR   UCSC; W06D4.1; c. elegans.
DR   AGR; WB:WBGene00001843; -.
DR   WormBase; W06D4.1; CE29602; WBGene00001843; hgo-1.
DR   eggNOG; KOG1417; Eukaryota.
DR   GeneTree; ENSGT00390000004601; -.
DR   HOGENOM; CLU_027174_0_0_1; -.
DR   InParanoid; Q9Y041; -.
DR   OMA; MLPHGPD; -.
DR   OrthoDB; 525at2759; -.
DR   PhylomeDB; Q9Y041; -.
DR   Reactome; R-CEL-8963684; Tyrosine catabolism.
DR   UniPathway; UPA00139; UER00339.
DR   PRO; PR:Q9Y041; -.
DR   Proteomes; UP000001940; Chromosome I.
DR   Bgee; WBGene00001843; Expressed in material anatomical entity and 5 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; HDA:WormBase.
DR   GO; GO:0055120; C:striated muscle dense body; HDA:WormBase.
DR   GO; GO:0004411; F:homogentisate 1,2-dioxygenase activity; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006559; P:L-phenylalanine catabolic process; IBA:GO_Central.
DR   GO; GO:0006572; P:tyrosine catabolic process; IEA:UniProtKB-KW.
DR   CDD; cd07000; cupin_HGO_N; 1.
DR   Gene3D; 2.60.120.10; Jelly Rolls; 1.
DR   InterPro; IPR046451; HgmA_C.
DR   InterPro; IPR046452; HgmA_N.
DR   InterPro; IPR005708; Homogentis_dOase.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   InterPro; IPR011051; RmlC_Cupin_sf.
DR   NCBIfam; TIGR01015; hmgA; 1.
DR   PANTHER; PTHR11056; HOMOGENTISATE 1,2-DIOXYGENASE; 1.
DR   PANTHER; PTHR11056:SF0; HOMOGENTISATE 1,2-DIOXYGENASE; 1.
DR   Pfam; PF04209; HgmA_C; 1.
DR   Pfam; PF20510; HgmA_N; 1.
DR   SUPFAM; SSF51182; RmlC-like cupins; 1.
PE   1: Evidence at protein level;
KW   Dioxygenase; Iron; Metal-binding; Oxidoreductase; Phenylalanine catabolism;
KW   Reference proteome; Tyrosine catabolism.
FT   CHAIN           1..437
FT                   /note="Homogentisate 1,2-dioxygenase"
FT                   /id="PRO_0000220243"
FT   REGION          15..34
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         336
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250"
FT   BINDING         342
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250"
FT   BINDING         372
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         173
FT                   /note="G->R: Suppresses fah-1 RNAi-mediated toxicity."
FT                   /evidence="ECO:0000269|PubMed:18227072"
FT   CONFLICT        156
FT                   /note="D -> N (in Ref. 2; AAD00776)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        176
FT                   /note="L -> P (in Ref. 2; AAD00776)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        193
FT                   /note="V -> G (in Ref. 2; AAD00776)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        242
FT                   /note="V -> G (in Ref. 2; AAD00776)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        265
FT                   /note="D -> E (in Ref. 2; AAD00776)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        433
FT                   /note="F -> Y (in Ref. 2; AAD00776)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   437 AA;  49239 MW;  C14E7077C7CF9703 CRC64;
     MSEFDELKYL TGFGNEHATS DPRVPDALPV GQNSPQKCSH GLYAEQLSGT AFTAPRSQNQ
     RSWLYRIRPS VIHRPFEAMK ENDQHWTNNF SSIPPNPNQY RWNPFPLPTK EGVTFVDNLY
     TVCGGGDVIS RTGLAIHQFS CNASMEHTAM YNSDGDFLIV PQQGALEITT EFGRLLVNPQ
     EIAVIPQGIR FSVAVRGPSR GYILEVYGTH FQLPDLGPIG ANGLANPRDF EAPVAWFEDL
     DVEFTIINKY QGSWFQAKQG HSPFDVVGWH GNYVPYKYDL KKFMVINTVS FDHCDPSIFT
     VLTAPSVKHG TAIADFVIFP PRWGCADNTF RPPYYHRNCM SEYMGLITGC YEAKEGGFKP
     GGGSLHSMMT PHGPDFNCFE MASNADLKPQ RVAEGTMSFM FESSLNMAIT NWAVYQNVDK
     DYYKDWQPLK KHFTMPK
//