HGD_HUMAN
ID HGD_HUMAN Reviewed; 445 AA.
AC Q93099; A8K417; B2R8Z0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Homogentisate 1,2-dioxygenase;
DE EC=1.13.11.5 {ECO:0000269|PubMed:8782815};
DE AltName: Full=Homogentisate oxygenase;
DE AltName: Full=Homogentisic acid oxidase;
DE AltName: Full=Homogentisicase;
GN Name=HGD; Synonyms=HGO;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-80; AKU SER-230 AND GLY-300,
RP CHARACTERIZATION OF VARIANT AKU SER-230, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8782815; DOI=10.1038/ng0996-19;
RA Fernandez-Canon J.M., Granadino B., Beltran-Valero de Bernabe D.,
RA Renedo M., Fernandez-Ruiz E., Penalva M.A., Rodriguez de Cordoba S.;
RT "The molecular basis of alkaptonuria.";
RL Nat. Genet. 14:19-24(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT HIS-80.
RC TISSUE=Liver;
RA Ramos S., Hernandez M., Rozes A., Larruga J., Gonzalez P., Cabrera V.M.;
RT "Homogentisate 1,2-dioxygenase human cDNA sequence.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-80.
RX PubMed=9244427; DOI=10.1006/geno.1997.4805;
RA Granadino B., Beltran-Valero de Bernabe D., Fernandez-Canon J.M.,
RA Penalva M.A., Rodriguez de Cordoba S.;
RT "The human homogentisate 1,2-dioxygenase (HGO) gene.";
RL Genomics 43:115-122(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-80.
RC TISSUE=Kidney, and Prostate;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT HIS-80.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-80.
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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-98, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), METAL-BINDING SITES, SUBUNIT, AND
RP COFACTOR.
RX PubMed=10876237; DOI=10.1038/76756;
RA Titus G.P., Mueller H.A., Burgner J., Rodriguez de Cordoba S.,
RA Penalva M.A., Timm D.E.;
RT "Crystal structure of human homogentisate dioxygenase.";
RL Nat. Struct. Biol. 7:542-546(2000).
RN [11]
RP VARIANT AKU ARG-161.
RX PubMed=9154114; DOI=10.1159/000134501;
RA Gehrig A., Schmidt S.R., Mueller C.R., Srsen S., Srsnova K., Kress W.;
RT "Molecular defects in alkaptonuria.";
RL Cytogenet. Cell Genet. 76:14-16(1997).
RN [12]
RP VARIANTS AKU ALA-42; GLY-97; GLY-153; ILE-189; THR-216; HIS-225; SER-227
RP AND VAL-368.
RX PubMed=9529363; DOI=10.1086/301805;
RA Beltran-Valero de Bernabe D., Granadino B., Chiarelli I., Porfirio B.,
RA Mayatepek E., Aquaron R., Moore M.M., Festen J.J.M., Sanmarti R.,
RA Penalva M.A., de Cordoba S.R.;
RT "Mutation and polymorphism analysis of the human homogentisate 1, 2-
RT dioxygenase gene in alkaptonuria patients.";
RL Am. J. Hum. Genet. 62:776-784(1998).
RN [13]
RP VARIANT AKU LYS-168.
RX PubMed=9630082; DOI=10.1111/j.1399-0004.1998.tb02684.x;
RA Higashino K., Liu W., Ohkawa T., Yamamoto T., Fukui K., Ohno M.,
RA Imanishi H., Iwasaki A., Amuro Y., Hada T.;
RT "A novel point mutation associated with alkaptonuria.";
RL Clin. Genet. 53:228-229(1998).
RN [14]
RP VARIANTS AKU GLY-60; CYS-62; ASP-122; THR-230 AND GLU-291.
RX PubMed=10205262; DOI=10.1086/302376;
RA Beltran-Valero de Bernabe D., Jimenez F.J., Aquaron R.,
RA Rodriguez de Cordoba S.;
RT "Analysis of alkaptonuria (AKU) mutations and polymorphisms reveals that
RT the CCC sequence motif is a mutational hot spot in the homogentisate 1,2
RT dioxygenase gene (HGO).";
RL Am. J. Hum. Genet. 64:1316-1322(1999).
RN [15]
RP VARIANTS AKU PRO-25 AND VAL-368.
RC TISSUE=Leukocyte;
RX PubMed=10340975; DOI=10.1136/bjo.83.6.680;
RA Felbor U., Mutsch Y., Grehn F., Mueller C.R., Kress W.;
RT "Ocular ochronosis in alkaptonuria patients carrying mutations in the
RT homogentisate 1,2-dioxygenase gene.";
RL Br. J. Ophthalmol. 83:680-683(1999).
RN [16]
RP VARIANTS AKU PRO-25; ARG-161; SER-230; ARG-270; GLY-300 AND VAL-368.
RC TISSUE=Lymphocyte;
RX PubMed=10482952; DOI=10.1038/sj.ejhg.5200343;
RA Mueller C.R., Fregin A., Srsen S., Srsnova K., Halliger-Keller B.,
RA Felbor U., Seemanova E., Kress W.;
RT "Allelic heterogeneity of alkaptonuria in Central Europe.";
RL Eur. J. Hum. Genet. 7:645-651(1999).
RN [17]
RP VARIANTS AKU SER-330; VAL-368 AND ARG-371.
RX PubMed=10594001;
RA Beltran-Valero de Bernabe D., Peterson P., Luopajarvi K., Matintalo P.,
RA Alho A., Konttinen Y., Krohn K., Rodriguez de Cordoba S., Ranki A.;
RT "Mutational analysis of the HGO gene in Finnish alkaptonuria patients.";
RL J. Med. Genet. 36:922-923(1999).
RN [18]
RP VARIANTS AKU ALA-3; ALA-42; GLY-60; PRO-61; CYS-62; LEU-73; THR-92; ARG-97;
RP PHE-120; TRP-120; VAL-122; ARG-123; PRO-137; LEU-158; ARG-161; ASP-168;
RP LYS-168; ARG-183; GLY-187; TRP-217; LEU-225; SER-230; PRO-258; ARG-269;
RP ARG-270; GLY-300; PRO-321; LEU-359; ARG-360; GLU-362; VAL-368; LEU-373 AND
RP GLN-401.
RX PubMed=19862842; DOI=10.1002/humu.21120;
RA Vilboux T., Kayser M., Introne W., Suwannarat P., Bernardini I.,
RA Fischer R., O'Brien K., Kleta R., Huizing M., Gahl W.A.;
RT "Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuria.";
RL Hum. Mutat. 30:1611-1619(2009).
RN [19]
RP VARIANTS AKU ARG-33; PHE-44; ARG-115; PRO-116; ALA-123; ALA-152; LEU-169;
RP GLY-178; GLY-197; SER-219; ASN-276; ALA-360; ARG-361 AND HIS-374.
RX PubMed=23430897; DOI=10.1007/8904_2011_68;
RA Zatkova A., Sedlackova T., Radvansky J., Polakova H., Nemethova M.,
RA Aquaron R., Dursun I., Usher J.L., Kadasi L.;
RT "Identification of 11 novel homogentisate 1,2 dioxygenase variants in
RT alkaptonuria patients and establishment of a novel LOVD-based HGD mutation
RT database.";
RL JIMD Rep. 4:55-65(2012).
RN [20]
RP VARIANTS AKU SER-227 AND ASN-369.
RX PubMed=21437689; DOI=10.1007/s00296-011-1868-0;
RA Al-sbou M.;
RT "Novel mutations in the homogentisate 1,2 dioxygenase gene identified in
RT Jordanian patients with alkaptonuria.";
RL Rheumatol. Int. 32:1741-1746(2012).
RN [21]
RP VARIANT AKU CYS-329.
RX PubMed=23353776; DOI=10.1016/j.gene.2013.01.020;
RA Yang Y.J., Guo J.H., Chen W.J., Zhao R., Tang J.S., Meng X.H., Zhao L.,
RA Tu M., He X.Y., Wu L.Q., Zhu Y.M.;
RT "First report of HGD mutations in a Chinese with alkaptonuria.";
RL Gene 518:467-469(2013).
RN [22]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-80, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP VARIANTS AKU LYS-13; ASN-18; ALA-42; GLN-53; ARG-115; PHE-120; ARG-123;
RP ARG-161; LEU-169; ASN-171; GLY-197; SER-219; HIS-225; PRO-225; SER-230;
RP PHE-245; ARG-270; ASN-276; GLY-300; ASP-337; LEU-359; ARG-360; ARG-361;
RP VAL-368 AND HIS-374, AND VARIANT THR-172.
RX PubMed=25681086; DOI=10.1007/8904_2014_380;
RA Usher J.L., Ascher D.B., Pires D.E., Milan A.M., Blundell T.L.,
RA Ranganath L.R.;
RT "Analysis of HGD gene mutations in patients with alkaptonuria from the
RT United Kingdom: identification of novel mutations.";
RL JIMD Rep. 24:3-11(2015).
CC -!- FUNCTION: Catalyzes the conversion of homogentisate to
CC maleylacetoacetate. {ECO:0000269|PubMed:8782815}.
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:8782815};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15450;
CC Evidence={ECO:0000305|PubMed:8782815};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:10876237};
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:0000269|PubMed:10876237}.
CC -!- INTERACTION:
CC Q93099; Q93099: HGD; NbExp=4; IntAct=EBI-3907760, EBI-3907760;
CC Q93099; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-3907760, EBI-741158;
CC Q93099; P54274: TERF1; NbExp=2; IntAct=EBI-3907760, EBI-710997;
CC -!- TISSUE SPECIFICITY: Highest expression in the prostate, small
CC intestine, colon, kidney and liver.
CC -!- DISEASE: Alkaptonuria (AKU) [MIM:203500]: An autosomal recessive error
CC of metabolism characterized by an increase in the level of homogentisic
CC acid. The clinical manifestations are urine that turns dark on standing
CC and alkalinization, black ochronotic pigmentation of cartilage and
CC collagenous tissues, and spine arthritis. {ECO:0000269|PubMed:10205262,
CC ECO:0000269|PubMed:10340975, ECO:0000269|PubMed:10482952,
CC ECO:0000269|PubMed:10594001, ECO:0000269|PubMed:19862842,
CC ECO:0000269|PubMed:21437689, ECO:0000269|PubMed:23353776,
CC ECO:0000269|PubMed:23430897, ECO:0000269|PubMed:25681086,
CC ECO:0000269|PubMed:8782815, ECO:0000269|PubMed:9154114,
CC ECO:0000269|PubMed:9529363, ECO:0000269|PubMed:9630082}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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; U63008; AAB16836.1; -; mRNA.
DR EMBL; Z75048; CAA99340.1; -; mRNA.
DR EMBL; AF000573; AAC51650.1; -; Genomic_DNA.
DR EMBL; AF045167; AAC02698.1; -; mRNA.
DR EMBL; AK290782; BAF83471.1; -; mRNA.
DR EMBL; AK313563; BAG36337.1; -; mRNA.
DR EMBL; AC126182; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133474; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79524.1; -; Genomic_DNA.
DR EMBL; BC071757; AAH71757.1; -; mRNA.
DR CCDS; CCDS3000.1; -.
DR RefSeq; NP_000178.2; NM_000187.3.
DR PDB; 1EY2; X-ray; 2.30 A; A=1-445.
DR PDB; 1EYB; X-ray; 1.90 A; A=1-445.
DR PDBsum; 1EY2; -.
DR PDBsum; 1EYB; -.
DR AlphaFoldDB; Q93099; -.
DR SMR; Q93099; -.
DR BioGRID; 109329; 7.
DR IntAct; Q93099; 6.
DR MINT; Q93099; -.
DR STRING; 9606.ENSP00000283871; -.
DR iPTMnet; Q93099; -.
DR PhosphoSitePlus; Q93099; -.
DR BioMuta; HGD; -.
DR jPOST; Q93099; -.
DR MassIVE; Q93099; -.
DR MaxQB; Q93099; -.
DR PaxDb; Q93099; -.
DR PeptideAtlas; Q93099; -.
DR PRIDE; Q93099; -.
DR ProteomicsDB; 75725; -.
DR Antibodypedia; 32802; 244 antibodies from 30 providers.
DR DNASU; 3081; -.
DR Ensembl; ENST00000283871.10; ENSP00000283871.5; ENSG00000113924.12.
DR GeneID; 3081; -.
DR KEGG; hsa:3081; -.
DR MANE-Select; ENST00000283871.10; ENSP00000283871.5; NM_000187.4; NP_000178.2.
DR UCSC; uc003edw.4; human.
DR CTD; 3081; -.
DR DisGeNET; 3081; -.
DR GeneCards; HGD; -.
DR GeneReviews; HGD; -.
DR HGNC; HGNC:4892; HGD.
DR HPA; ENSG00000113924; Group enriched (kidney, liver).
DR MalaCards; HGD; -.
DR MIM; 203500; phenotype.
DR MIM; 607474; gene.
DR neXtProt; NX_Q93099; -.
DR OpenTargets; ENSG00000113924; -.
DR Orphanet; 56; Alkaptonuria.
DR PharmGKB; PA29268; -.
DR VEuPathDB; HostDB:ENSG00000113924; -.
DR eggNOG; KOG1417; Eukaryota.
DR GeneTree; ENSGT00390000004601; -.
DR HOGENOM; CLU_027174_0_0_1; -.
DR InParanoid; Q93099; -.
DR OMA; FMFETRW; -.
DR OrthoDB; 795654at2759; -.
DR PhylomeDB; Q93099; -.
DR TreeFam; TF300490; -.
DR BioCyc; MetaCyc:HS03728-MON; -.
DR BRENDA; 1.13.11.5; 2681.
DR PathwayCommons; Q93099; -.
DR Reactome; R-HSA-8963684; Tyrosine catabolism.
DR SignaLink; Q93099; -.
DR UniPathway; UPA00139; UER00339.
DR BioGRID-ORCS; 3081; 13 hits in 1066 CRISPR screens.
DR ChiTaRS; HGD; human.
DR EvolutionaryTrace; Q93099; -.
DR GenomeRNAi; 3081; -.
DR Pharos; Q93099; Tbio.
DR PRO; PR:Q93099; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q93099; protein.
DR Bgee; ENSG00000113924; Expressed in right lobe of liver and 140 other tissues.
DR ExpressionAtlas; Q93099; baseline and differential.
DR Genevisible; Q93099; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0004411; F:homogentisate 1,2-dioxygenase activity; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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; TAS:ProtInc.
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 3D-structure; Acetylation; Dioxygenase; Disease variant; Iron;
KW Metal-binding; Oxidoreductase; Phenylalanine catabolism;
KW Reference proteome; Tyrosine catabolism.
FT CHAIN 1..445
FT /note="Homogentisate 1,2-dioxygenase"
FT /id="PRO_0000220240"
FT BINDING 335
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:10876237,
FT ECO:0007744|PDB:1EY2"
FT BINDING 341
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:10876237,
FT ECO:0007744|PDB:1EY2"
FT BINDING 371
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:10876237,
FT ECO:0007744|PDB:1EY2"
FT MOD_RES 98
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 414
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O09173"
FT VARIANT 3
FT /note="E -> A (in AKU; dbSNP:rs200412910)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073076"
FT VARIANT 13
FT /note="E -> K (in AKU; dbSNP:rs1458752246)"
FT /evidence="ECO:0000269|PubMed:25681086"
FT /id="VAR_073077"
FT VARIANT 18
FT /note="D -> N (in AKU)"
FT /evidence="ECO:0000269|PubMed:25681086"
FT /id="VAR_073078"
FT VARIANT 25
FT /note="L -> P (in AKU)"
FT /evidence="ECO:0000269|PubMed:10340975,
FT ECO:0000269|PubMed:10482952"
FT /id="VAR_009618"
FT VARIANT 33
FT /note="Q -> R (in AKU)"
FT /evidence="ECO:0000269|PubMed:23430897"
FT /id="VAR_073079"
FT VARIANT 42
FT /note="E -> A (in AKU; dbSNP:rs373921680)"
FT /evidence="ECO:0000269|PubMed:19862842,
FT ECO:0000269|PubMed:25681086, ECO:0000269|PubMed:9529363"
FT /id="VAR_005272"
FT VARIANT 44
FT /note="L -> F (in AKU; dbSNP:rs1049246177)"
FT /evidence="ECO:0000269|PubMed:23430897"
FT /id="VAR_073080"
FT VARIANT 53
FT /note="R -> Q (in AKU; dbSNP:rs200808744)"
FT /evidence="ECO:0000269|PubMed:25681086"
FT /id="VAR_073081"
FT VARIANT 60
FT /note="W -> G (in AKU)"
FT /evidence="ECO:0000269|PubMed:10205262,
FT ECO:0000269|PubMed:19862842"
FT /id="VAR_005273"
FT VARIANT 61
FT /note="L -> P (in AKU; dbSNP:rs1324654414)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073082"
FT VARIANT 62
FT /note="Y -> C (in AKU; dbSNP:rs1174584850)"
FT /evidence="ECO:0000269|PubMed:10205262,
FT ECO:0000269|PubMed:19862842"
FT /id="VAR_005274"
FT VARIANT 73
FT /note="F -> L (in AKU)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073083"
FT VARIANT 80
FT /note="Q -> H (in dbSNP:rs2255543)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8782815,
FT ECO:0000269|PubMed:9244427, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.6, ECO:0007744|PubMed:24275569"
FT /id="VAR_049353"
FT VARIANT 92
FT /note="P -> T (in AKU)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073084"
FT VARIANT 97
FT /note="W -> G (in AKU)"
FT /evidence="ECO:0000269|PubMed:9529363"
FT /id="VAR_005275"
FT VARIANT 97
FT /note="W -> R (in AKU)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073085"
FT VARIANT 115
FT /note="G -> R (in AKU; dbSNP:rs755734596)"
FT /evidence="ECO:0000269|PubMed:23430897,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073086"
FT VARIANT 116
FT /note="L -> P (in AKU; dbSNP:rs569846003)"
FT /evidence="ECO:0000269|PubMed:23430897"
FT /id="VAR_073087"
FT VARIANT 120
FT /note="C -> F (in AKU; dbSNP:rs752153829)"
FT /evidence="ECO:0000269|PubMed:19862842,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073088"
FT VARIANT 120
FT /note="C -> W (in AKU; dbSNP:rs149165166)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073089"
FT VARIANT 122
FT /note="A -> D (in AKU)"
FT /evidence="ECO:0000269|PubMed:10205262"
FT /id="VAR_005276"
FT VARIANT 122
FT /note="A -> V (in AKU; dbSNP:rs544956641)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073090"
FT VARIANT 123
FT /note="G -> A (in AKU; dbSNP:rs374473331)"
FT /evidence="ECO:0000269|PubMed:23430897"
FT /id="VAR_073091"
FT VARIANT 123
FT /note="G -> R (in AKU; dbSNP:rs564979861)"
FT /evidence="ECO:0000269|PubMed:19862842,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073092"
FT VARIANT 137
FT /note="L -> P (in AKU)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073093"
FT VARIANT 152
FT /note="G -> A (in AKU; dbSNP:rs1553717936)"
FT /evidence="ECO:0000269|PubMed:23430897"
FT /id="VAR_073094"
FT VARIANT 153
FT /note="D -> G (in AKU; dbSNP:rs775274569)"
FT /evidence="ECO:0000269|PubMed:9529363"
FT /id="VAR_005277"
FT VARIANT 158
FT /note="P -> L (in AKU; dbSNP:rs375396766)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073095"
FT VARIANT 161
FT /note="G -> R (in AKU; loss of activity; most prevalent
FT mutation in Slovak and Czech patients; dbSNP:rs28941783)"
FT /evidence="ECO:0000269|PubMed:10482952,
FT ECO:0000269|PubMed:19862842, ECO:0000269|PubMed:25681086,
FT ECO:0000269|PubMed:9154114"
FT /id="VAR_005278"
FT VARIANT 168
FT /note="E -> D (in AKU; dbSNP:rs780173554)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073096"
FT VARIANT 168
FT /note="E -> K (in AKU; loss of activity;
FT dbSNP:rs375283568)"
FT /evidence="ECO:0000269|PubMed:19862842,
FT ECO:0000269|PubMed:9630082"
FT /id="VAR_009619"
FT VARIANT 169
FT /note="F -> L (in AKU; dbSNP:rs756134838)"
FT /evidence="ECO:0000269|PubMed:23430897,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073097"
FT VARIANT 171
FT /note="K -> N (in AKU)"
FT /evidence="ECO:0000269|PubMed:25681086"
FT /id="VAR_073098"
FT VARIANT 172
FT /note="M -> T"
FT /evidence="ECO:0000269|PubMed:25681086"
FT /id="VAR_073099"
FT VARIANT 178
FT /note="E -> G (in AKU)"
FT /evidence="ECO:0000269|PubMed:23430897"
FT /id="VAR_073100"
FT VARIANT 183
FT /note="Q -> R (in AKU; dbSNP:rs1349543050)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073101"
FT VARIANT 187
FT /note="R -> G (in AKU; dbSNP:rs756255206)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073102"
FT VARIANT 189
FT /note="S -> I (in AKU)"
FT /evidence="ECO:0000269|PubMed:9529363"
FT /id="VAR_005279"
FT VARIANT 197
FT /note="R -> G (in AKU; dbSNP:rs1414279737)"
FT /evidence="ECO:0000269|PubMed:23430897,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073103"
FT VARIANT 216
FT /note="I -> T (in AKU; dbSNP:rs767201131)"
FT /evidence="ECO:0000269|PubMed:9529363"
FT /id="VAR_005280"
FT VARIANT 217
FT /note="G -> W (in AKU)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073104"
FT VARIANT 219
FT /note="N -> S (in AKU)"
FT /evidence="ECO:0000269|PubMed:23430897,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073105"
FT VARIANT 225
FT /note="R -> H (in AKU; dbSNP:rs562853291)"
FT /evidence="ECO:0000269|PubMed:25681086,
FT ECO:0000269|PubMed:9529363"
FT /id="VAR_005281"
FT VARIANT 225
FT /note="R -> L (in AKU)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073106"
FT VARIANT 225
FT /note="R -> P (in AKU; dbSNP:rs562853291)"
FT /evidence="ECO:0000269|PubMed:25681086"
FT /id="VAR_073107"
FT VARIANT 227
FT /note="F -> S (in AKU)"
FT /evidence="ECO:0000269|PubMed:21437689,
FT ECO:0000269|PubMed:9529363"
FT /id="VAR_005282"
FT VARIANT 230
FT /note="P -> S (in AKU; complete loss of activity;
FT dbSNP:rs28942100)"
FT /evidence="ECO:0000269|PubMed:10482952,
FT ECO:0000269|PubMed:19862842, ECO:0000269|PubMed:25681086,
FT ECO:0000269|PubMed:8782815"
FT /id="VAR_005283"
FT VARIANT 230
FT /note="P -> T (in AKU)"
FT /evidence="ECO:0000269|PubMed:10205262"
FT /id="VAR_005284"
FT VARIANT 245
FT /note="V -> F (in AKU)"
FT /evidence="ECO:0000269|PubMed:25681086"
FT /id="VAR_073108"
FT VARIANT 258
FT /note="Q -> P (in AKU; dbSNP:rs759843592)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073109"
FT VARIANT 269
FT /note="H -> R (in AKU; dbSNP:rs756522409)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073110"
FT VARIANT 270
FT /note="G -> R (in AKU; dbSNP:rs120074174)"
FT /evidence="ECO:0000269|PubMed:10482952,
FT ECO:0000269|PubMed:19862842, ECO:0000269|PubMed:25681086"
FT /id="VAR_009620"
FT VARIANT 276
FT /note="K -> N (in AKU; dbSNP:rs1160502581)"
FT /evidence="ECO:0000269|PubMed:23430897,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073111"
FT VARIANT 291
FT /note="D -> E (in AKU; dbSNP:rs754428438)"
FT /evidence="ECO:0000269|PubMed:10205262"
FT /id="VAR_005285"
FT VARIANT 300
FT /note="V -> G (in AKU; dbSNP:rs120074170)"
FT /evidence="ECO:0000269|PubMed:10482952,
FT ECO:0000269|PubMed:19862842, ECO:0000269|PubMed:25681086,
FT ECO:0000269|PubMed:8782815"
FT /id="VAR_005286"
FT VARIANT 321
FT /note="R -> P (in AKU)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073112"
FT VARIANT 329
FT /note="F -> C (in AKU)"
FT /evidence="ECO:0000269|PubMed:23353776"
FT /id="VAR_073113"
FT VARIANT 330
FT /note="R -> S (in AKU; dbSNP:rs120074171)"
FT /evidence="ECO:0000269|PubMed:10594001"
FT /id="VAR_008744"
FT VARIANT 337
FT /note="N -> D (in AKU)"
FT /evidence="ECO:0000269|PubMed:25681086"
FT /id="VAR_073114"
FT VARIANT 359
FT /note="P -> L (in AKU; dbSNP:rs764037565)"
FT /evidence="ECO:0000269|PubMed:19862842,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073115"
FT VARIANT 360
FT /note="G -> A (in AKU)"
FT /evidence="ECO:0000269|PubMed:23430897"
FT /id="VAR_073116"
FT VARIANT 360
FT /note="G -> R (in AKU; dbSNP:rs368717991)"
FT /evidence="ECO:0000269|PubMed:19862842,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073117"
FT VARIANT 361
FT /note="G -> R (in AKU; dbSNP:rs765219004)"
FT /evidence="ECO:0000269|PubMed:23430897,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073118"
FT VARIANT 362
FT /note="G -> E (in AKU)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073119"
FT VARIANT 368
FT /note="M -> V (in AKU; loss of activity;
FT dbSNP:rs120074173)"
FT /evidence="ECO:0000269|PubMed:10340975,
FT ECO:0000269|PubMed:10482952, ECO:0000269|PubMed:10594001,
FT ECO:0000269|PubMed:19862842, ECO:0000269|PubMed:25681086,
FT ECO:0000269|PubMed:9529363"
FT /id="VAR_005287"
FT VARIANT 369
FT /note="T -> N (in AKU; dbSNP:rs765912447)"
FT /evidence="ECO:0000269|PubMed:21437689"
FT /id="VAR_073120"
FT VARIANT 371
FT /note="H -> R (in AKU; dbSNP:rs120074172)"
FT /evidence="ECO:0000269|PubMed:10594001"
FT /id="VAR_008745"
FT VARIANT 373
FT /note="P -> L (in AKU; dbSNP:rs138558042)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073121"
FT VARIANT 374
FT /note="D -> H (in AKU; dbSNP:rs981454067)"
FT /evidence="ECO:0000269|PubMed:23430897,
FT ECO:0000269|PubMed:25681086"
FT /id="VAR_073122"
FT VARIANT 401
FT /note="E -> Q (in AKU; dbSNP:rs767159114)"
FT /evidence="ECO:0000269|PubMed:19862842"
FT /id="VAR_073123"
FT CONFLICT 383
FT /note="K -> R (in Ref. 4; BAF83471)"
FT /evidence="ECO:0000305"
FT STRAND 6..8
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 58..65
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:1EYB"
FT TURN 105..107
FT /evidence="ECO:0007829|PDB:1EYB"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 116..123
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 131..138
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 144..161
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 170..174
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 178..182
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 193..205
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 238..249
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 252..260
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 265..271
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 275..278
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 288..291
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 295..298
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 299..304
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 311..318
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 320..323
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 340..347
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 375..383
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:1EYB"
FT STRAND 396..404
FT /evidence="ECO:0007829|PDB:1EYB"
FT HELIX 410..415
FT /evidence="ECO:0007829|PDB:1EYB"
SQ SEQUENCE 445 AA; 49964 MW; F99B51C134FFF965 CRC64;
MAELKYISGF GNECSSEDPR CPGSLPEGQN NPQVCPYNLY AEQLSGSAFT CPRSTNKRSW
LYRILPSVSH KPFESIDEGQ VTHNWDEVDP DPNQLRWKPF EIPKASQKKV DFVSGLHTLC
GAGDIKSNNG LAIHIFLCNT SMENRCFYNS DGDFLIVPQK GNLLIYTEFG KMLVQPNEIC
VIQRGMRFSI DVFEETRGYI LEVYGVHFEL PDLGPIGANG LANPRDFLIP IAWYEDRQVP
GGYTVINKYQ GKLFAAKQDV SPFNVVAWHG NYTPYKYNLK NFMVINSVAF DHADPSIFTV
LTAKSVRPGV AIADFVIFPP RWGVADKTFR PPYYHRNCMS EFMGLIRGHY EAKQGGFLPG
GGSLHSTMTP HGPDADCFEK ASKVKLAPER IADGTMAFMF ESSLSLAVTK WGLKASRCLD
ENYHKCWEPL KSHFTPNSRN PAEPN
