HGD_MOUSE
ID HGD_MOUSE Reviewed; 445 AA.
AC O09173; Q7TPP2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Homogentisate 1,2-dioxygenase;
DE EC=1.13.11.5 {ECO:0000269|PubMed:7705358};
DE AltName: Full=Homogentisate oxygenase;
DE AltName: Full=Homogentisic acid oxidase;
DE AltName: Full=Homogentisicase;
GN Name=Hgd; Synonyms=Aku, Hgo;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=9069115; DOI=10.1007/s003359900383;
RA Schmidt S.R., Gehrig A., Koehler M.R., Schmid M., Mueller C.R., Kress W.;
RT "Cloning of the homogentisate 1,2-dioxygenase gene, the key enzyme of
RT alkaptonuria in mouse.";
RL Mamm. Genome 8:168-171(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RC TISSUE=Liver;
RX PubMed=7705358; DOI=10.1111/j.1432-1033.1995.00425.x;
RA Schmidt S.R., Muller C.R., Kress W.;
RT "Murine liver homogentisate 1,2-dioxygenase. Purification to homogeneity
RT and novel biochemical properties.";
RL Eur. J. Biochem. 228:425-430(1995).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-414, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Catalyzes the conversion of homogentisate to
CC maleylacetoacetate. {ECO:0000269|PubMed:7705358}.
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 Evidence={ECO:0000269|PubMed:7705358};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15450;
CC Evidence={ECO:0000269|PubMed:7705358};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:7705358};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=188 uM for homogentisate {ECO:0000269|PubMed:7705358};
CC pH dependence:
CC Optimum pH is 6.1. {ECO:0000269|PubMed:7705358};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 4/6.
CC -!- SUBUNIT: Homohexamer arranged as a dimer of trimers.
CC {ECO:0000250|UniProtKB:Q93099}.
CC -!- DISEASE: Note=Defects in Hgd are the cause of alkaptonuria (aku). Aku
CC is an autosomal recessive error of metabolism which is characterized by
CC an increase in the level of homogentisic acid.
CC -!- SIMILARITY: Belongs to the homogentisate dioxygenase family.
CC {ECO:0000305}.
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DR EMBL; U58988; AAC53224.1; -; mRNA.
DR EMBL; CH466521; EDK97961.1; -; Genomic_DNA.
DR EMBL; BC055029; AAH55029.1; -; mRNA.
DR CCDS; CCDS49849.1; -.
DR RefSeq; NP_038575.2; NM_013547.3.
DR AlphaFoldDB; O09173; -.
DR SMR; O09173; -.
DR BioGRID; 200293; 1.
DR STRING; 10090.ENSMUSP00000125492; -.
DR iPTMnet; O09173; -.
DR PhosphoSitePlus; O09173; -.
DR SwissPalm; O09173; -.
DR jPOST; O09173; -.
DR MaxQB; O09173; -.
DR PaxDb; O09173; -.
DR PeptideAtlas; O09173; -.
DR PRIDE; O09173; -.
DR ProteomicsDB; 269784; -.
DR Antibodypedia; 32802; 244 antibodies from 30 providers.
DR DNASU; 15233; -.
DR Ensembl; ENSMUST00000160847; ENSMUSP00000125492; ENSMUSG00000022821.
DR GeneID; 15233; -.
DR KEGG; mmu:15233; -.
DR UCSC; uc007zeg.2; mouse.
DR CTD; 3081; -.
DR MGI; MGI:96078; Hgd.
DR VEuPathDB; HostDB:ENSMUSG00000022821; -.
DR eggNOG; KOG1417; Eukaryota.
DR GeneTree; ENSGT00390000004601; -.
DR HOGENOM; CLU_027174_0_0_1; -.
DR InParanoid; O09173; -.
DR OMA; FMFETRW; -.
DR OrthoDB; 795654at2759; -.
DR PhylomeDB; O09173; -.
DR TreeFam; TF300490; -.
DR Reactome; R-MMU-8963684; Tyrosine catabolism.
DR SABIO-RK; O09173; -.
DR UniPathway; UPA00139; UER00339.
DR BioGRID-ORCS; 15233; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Hgd; mouse.
DR PRO; PR:O09173; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; O09173; protein.
DR Bgee; ENSMUSG00000022821; Expressed in left lobe of liver and 95 other tissues.
DR ExpressionAtlas; O09173; baseline and differential.
DR Genevisible; O09173; MM.
DR GO; GO:0004411; F:homogentisate 1,2-dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006520; P:cellular amino acid metabolic process; IMP:MGI.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IBA:GO_Central.
DR GO; GO:0006572; P:tyrosine catabolic process; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR005708; Homogentis_dOase.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR PANTHER; PTHR11056; PTHR11056; 1.
DR Pfam; PF04209; HgmA; 1.
DR SUPFAM; SSF51182; SSF51182; 1.
DR TIGRFAMs; TIGR01015; hmgA; 1.
PE 1: Evidence at protein level;
KW Acetylation; Dioxygenase; Direct protein sequencing; Iron; Metal-binding;
KW Oxidoreductase; Phenylalanine catabolism; Reference proteome;
KW Tyrosine catabolism.
FT CHAIN 1..445
FT /note="Homogentisate 1,2-dioxygenase"
FT /id="PRO_0000220241"
FT BINDING 335
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q93099"
FT BINDING 341
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q93099"
FT BINDING 371
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q93099"
FT MOD_RES 98
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q93099"
FT MOD_RES 414
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 267
FT /note="A -> T (in Ref. 1; AAC53224)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 445 AA; 49960 MW; 27DEB34D38DB1C25 CRC64;
MAELKYISGF GNECASEDPR CPGSLPKGQN NPQVCPYNLY AEQLSGSAFT CPRNTNKRSW
LYRILPSVSH KPFESIDQGH VTHNWDEVGP DPNQLRWKPF EIPKASEKKV DFVSGLYTLC
GAGDIKSNNG LAVHIFLCNS SMENRCFYNS DGDFLIVPQK GKLLIYTEFG KMSLQPNEIC
VIQRGMRFSV DVFEETRGYI LEVYGVHFEL PDLGPIGANG LANPRDFLIP VAWYEDRRVP
GGYTVINKFQ GKLFACKQDV SPFNVVAWHG NYTPYKYNLE NFMVINAVAF DHADPSIFTV
LTAKSLRPGV AIADFVIFPP RWGVADKTFR PPYYHRNCMS EFMGLIKGHY EAKQGGFLPG
GGSLHSAMTP HGPDADCFEK ASKAKLEPER IADGTMAFMF ESSLSLAVTK WGLKTCSCLD
ENYYKCWEPL RSHFTPNSRS PTEPK
