HPPD_HUMAN
ID HPPD_HUMAN Reviewed; 393 AA.
AC P32754; A8K461; B3KQ63; Q13234;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=4-hydroxyphenylpyruvate dioxygenase;
DE EC=1.13.11.27 {ECO:0000269|PubMed:1339442};
DE AltName: Full=4-hydroxyphenylpyruvic acid oxidase;
DE Short=4HPPD;
DE Short=HPD;
DE Short=HPPDase;
GN Name=HPD; Synonyms=PPD;
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 [GENOMIC DNA] (ISOFORM 1).
RX PubMed=7851880; DOI=10.1006/geno.1994.1540;
RA Awata H., Endo F., Matsuda I.;
RT "Structure of the human 4-hydroxyphenylpyruvic acid dioxygenase gene
RT (HPD).";
RL Genomics 23:534-539(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8521727; DOI=10.1159/000134142;
RA Stenman G., Roijer E., Rueetschi U., Dellsen A., Rymo L., Lindstedt S.;
RT "Regional assignment of the human 4-hydroxyphenylpyruvate dioxygenase gene
RT (HPD) to 12q24-->qter by fluorescence in situ hybridization.";
RL Cytogenet. Cell Genet. 71:374-376(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=9325050; DOI=10.1006/geno.1997.4887;
RA Ruetschi U., Rymo L., Lindstedt S.;
RT "Human 4-hydroxyphenylpyruvate dioxygenase gene (HPD).";
RL Genomics 44:292-299(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver, and Testis;
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=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC 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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=1339442; DOI=10.1016/s0021-9258(18)35755-7;
RA Endo F., Awata H., Tanoue A., Ishiguro M., Eda Y., Titani K., Matsuda I.;
RT "Primary structure deduced from complementary DNA sequence and expression
RT in cultured cells of mammalian 4-hydroxyphenylpyruvic acid dioxygenase.
RT Evidence that the enzyme is a homodimer of identical subunits homologous to
RT rat liver-specific alloantigen F.";
RL J. Biol. Chem. 267:24235-24240(1992).
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 ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, AND IDENTIFICATION BY
RP MASS 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 [12]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 8-393 IN COMPLEX WITH COBALT
RP IONS.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human 4-hydroxyphenylpyruvate dioxygenase.";
RL Submitted (SEP-2009) to the PDB data bank.
RN [13]
RP VARIANTS TYRSN3 CYS-160 AND MET-335, AND VARIANTS THR-33; PHE-267 AND
RP LEU-340.
RX PubMed=10942115; DOI=10.1007/s004390000307;
RA Rueetschi U., Cerone R., Perez-Cerda C., Schiaffino M.C., Standing S.,
RA Ugarte M., Holme E.;
RT "Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in
RT patients with tyrosinemia type III.";
RL Hum. Genet. 106:654-662(2000).
RN [14]
RP VARIANT TYRSN3 VAL-268, AND VARIANT HAWK THR-33.
RX PubMed=11073718; DOI=10.1006/mgme.2000.3085;
RA Tomoeda K., Awata H., Matsuura T., Matsuda I., Ploechl E., Milovac T.,
RA Boneh A., Scott C.R., Danks D.M., Endo F.;
RT "Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are
RT responsible for tyrosinemia type III and hawkinsinuria.";
RL Mol. Genet. Metab. 71:506-510(2000).
CC -!- FUNCTION: Catalyzes the conversion of 4-hydroxyphenylpyruvic acid to
CC homogentisic acid, one of the steps in tyrosine catabolism.
CC {ECO:0000269|PubMed:1339442}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(4-hydroxyphenyl)pyruvate + O2 = CO2 + homogentisate;
CC Xref=Rhea:RHEA:16189, ChEBI:CHEBI:15379, ChEBI:CHEBI:16169,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:36242; EC=1.13.11.27;
CC Evidence={ECO:0000269|PubMed:1339442};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16190;
CC Evidence={ECO:0000305|PubMed:1339442};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:P32755};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000250|UniProtKB:P32755};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 3/6.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:1339442, ECO:0000269|Ref.12}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P32755}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P32755};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P32755}. Golgi
CC apparatus membrane {ECO:0000250|UniProtKB:P32755}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:P32755}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P32754-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32754-2; Sequence=VSP_044302;
CC -!- DISEASE: Tyrosinemia 3 (TYRSN3) [MIM:276710]: An inborn error of
CC metabolism characterized by elevations of tyrosine in the blood and
CC urine, seizures and mild intellectual disability.
CC {ECO:0000269|PubMed:10942115, ECO:0000269|PubMed:11073718}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hawkinsinuria (HAWK) [MIM:140350]: An inborn error of tyrosine
CC metabolism characterized by failure to thrive, persistent metabolic
CC acidosis, fine and sparse hair, and excretion of the unusual cyclic
CC amino acid metabolite, hawkinsin, in the urine.
CC {ECO:0000269|PubMed:11073718}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the 4HPPD family. {ECO:0000305}.
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DR EMBL; D31628; BAA06498.1; -; Genomic_DNA.
DR EMBL; X72389; CAA51082.1; -; mRNA.
DR EMBL; U29895; AAC73008.1; -; Genomic_DNA.
DR EMBL; AK057510; BAG51925.1; -; mRNA.
DR EMBL; AK290826; BAF83515.1; -; mRNA.
DR EMBL; AC069503; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079360; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW98292.1; -; Genomic_DNA.
DR EMBL; BC024287; AAH24287.1; -; mRNA.
DR CCDS; CCDS53839.1; -. [P32754-2]
DR CCDS; CCDS9224.1; -. [P32754-1]
DR PIR; S32458; S32458.
DR RefSeq; NP_001165464.1; NM_001171993.1. [P32754-2]
DR RefSeq; NP_002141.1; NM_002150.2.
DR PDB; 3ISQ; X-ray; 1.75 A; A=8-393.
DR PDB; 5EC3; X-ray; 2.10 A; A=1-393.
DR PDBsum; 3ISQ; -.
DR PDBsum; 5EC3; -.
DR AlphaFoldDB; P32754; -.
DR SMR; P32754; -.
DR BioGRID; 109482; 17.
DR IntAct; P32754; 6.
DR STRING; 9606.ENSP00000289004; -.
DR BindingDB; P32754; -.
DR ChEMBL; CHEMBL1861; -.
DR DrugBank; DB02850; DAS869.
DR DrugBank; DB00348; Nitisinone.
DR DrugCentral; P32754; -.
DR iPTMnet; P32754; -.
DR PhosphoSitePlus; P32754; -.
DR BioMuta; HPD; -.
DR DMDM; 417144; -.
DR jPOST; P32754; -.
DR MassIVE; P32754; -.
DR MaxQB; P32754; -.
DR PaxDb; P32754; -.
DR PeptideAtlas; P32754; -.
DR PRIDE; P32754; -.
DR ProteomicsDB; 3550; -.
DR ProteomicsDB; 54881; -. [P32754-1]
DR Antibodypedia; 31595; 328 antibodies from 31 providers.
DR DNASU; 3242; -.
DR Ensembl; ENST00000543163.5; ENSP00000441677.1; ENSG00000158104.11. [P32754-2]
DR GeneID; 3242; -.
DR KEGG; hsa:3242; -.
DR UCSC; uc058ujk.1; human. [P32754-1]
DR CTD; 3242; -.
DR DisGeNET; 3242; -.
DR GeneCards; HPD; -.
DR HGNC; HGNC:5147; HPD.
DR HPA; ENSG00000158104; Tissue enriched (liver).
DR MalaCards; HPD; -.
DR MIM; 140350; phenotype.
DR MIM; 276710; phenotype.
DR MIM; 609695; gene.
DR neXtProt; NX_P32754; -.
DR OpenTargets; ENSG00000158104; -.
DR Orphanet; 2118; Hawkinsinuria.
DR Orphanet; 69723; Tyrosinemia type 3.
DR PharmGKB; PA29420; -.
DR VEuPathDB; HostDB:ENSG00000158104; -.
DR eggNOG; KOG0638; Eukaryota.
DR GeneTree; ENSGT00530000063474; -.
DR HOGENOM; CLU_034004_3_1_1; -.
DR InParanoid; P32754; -.
DR OrthoDB; 1087836at2759; -.
DR PhylomeDB; P32754; -.
DR BioCyc; MetaCyc:HS08267-MON; -.
DR BRENDA; 1.13.11.27; 2681.
DR PathwayCommons; P32754; -.
DR Reactome; R-HSA-8963684; Tyrosine catabolism.
DR SignaLink; P32754; -.
DR UniPathway; UPA00139; UER00362.
DR BioGRID-ORCS; 3242; 13 hits in 1070 CRISPR screens.
DR ChiTaRS; HPD; human.
DR EvolutionaryTrace; P32754; -.
DR GenomeRNAi; 3242; -.
DR Pharos; P32754; Tclin.
DR PRO; PR:P32754; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P32754; protein.
DR Bgee; ENSG00000158104; Expressed in right lobe of liver and 103 other tissues.
DR ExpressionAtlas; P32754; baseline and differential.
DR Genevisible; P32754; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IBA:GO_Central.
DR GO; GO:0003868; F:4-hydroxyphenylpyruvate dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006572; P:tyrosine catabolic process; IDA:MGI.
DR CDD; cd07250; HPPD_C_like; 1.
DR CDD; cd08342; HPPD_N_like; 1.
DR Gene3D; 3.10.180.10; -; 2.
DR InterPro; IPR005956; 4OHPhenylPyrv_dOase.
DR InterPro; IPR041735; 4OHPhenylPyrv_dOase_C.
DR InterPro; IPR041736; 4OHPhenylPyrv_dOase_N.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR037523; VOC.
DR PANTHER; PTHR11959; PTHR11959; 1.
DR Pfam; PF00903; Glyoxalase; 1.
DR PIRSF; PIRSF009283; HPP_dOase; 1.
DR SUPFAM; SSF54593; SSF54593; 1.
DR TIGRFAMs; TIGR01263; 4HPPD; 1.
DR PROSITE; PS51819; VOC; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Dioxygenase;
KW Disease variant; Endoplasmic reticulum; Golgi apparatus;
KW Intellectual disability; Iron; Membrane; Metal-binding; Oxidoreductase;
KW Phenylalanine catabolism; Phosphoprotein; Reference proteome; Repeat;
KW Tyrosine catabolism.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..393
FT /note="4-hydroxyphenylpyruvate dioxygenase"
FT /id="PRO_0000088388"
FT DOMAIN 18..149
FT /note="VOC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT DOMAIN 180..338
FT /note="VOC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT BINDING 183
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000305"
FT BINDING 266
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000305"
FT BINDING 349
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000305"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 132
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49429"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49429"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49429"
FT VAR_SEQ 1..39
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044302"
FT VARIANT 33
FT /note="A -> T (in two patients with hawkinsinuria;
FT dbSNP:rs1154510)"
FT /evidence="ECO:0000269|PubMed:10942115,
FT ECO:0000269|PubMed:11073718"
FT /id="VAR_015444"
FT VARIANT 113
FT /note="R -> Q (in dbSNP:rs11833399)"
FT /id="VAR_048101"
FT VARIANT 160
FT /note="Y -> C (in TYRSN3; dbSNP:rs137852865)"
FT /evidence="ECO:0000269|PubMed:10942115"
FT /id="VAR_015445"
FT VARIANT 267
FT /note="I -> F"
FT /evidence="ECO:0000269|PubMed:10942115"
FT /id="VAR_015446"
FT VARIANT 268
FT /note="A -> V (in TYRSN3)"
FT /evidence="ECO:0000269|PubMed:11073718"
FT /id="VAR_015447"
FT VARIANT 335
FT /note="I -> M (in TYRSN3)"
FT /evidence="ECO:0000269|PubMed:10942115"
FT /id="VAR_015448"
FT VARIANT 340
FT /note="V -> L (in dbSNP:rs36023382)"
FT /evidence="ECO:0000269|PubMed:10942115"
FT /id="VAR_015449"
FT CONFLICT 162
FT /note="A -> P (in Ref. 3; AAC73008)"
FT /evidence="ECO:0000305"
FT STRAND 15..25
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 29..40
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 56..64
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 67..76
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 80..89
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 91..101
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 103..113
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 117..126
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 129..137
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 178..187
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 193..204
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 207..212
FT /evidence="ECO:0007829|PDB:3ISQ"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 223..230
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 237..244
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 251..259
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 261..272
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 274..283
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 293..303
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 314..320
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 323..326
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 331..337
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:3ISQ"
FT STRAND 347..355
FT /evidence="ECO:0007829|PDB:3ISQ"
FT HELIX 361..377
FT /evidence="ECO:0007829|PDB:3ISQ"
SQ SEQUENCE 393 AA; 44934 MW; 4314A16532C33A2F CRC64;
MTTYSDKGAK PERGRFLHFH SVTFWVGNAK QAASFYCSKM GFEPLAYRGL ETGSREVVSH
VIKQGKIVFV LSSALNPWNK EMGDHLVKHG DGVKDIAFEV EDCDYIVQKA RERGAKIMRE
PWVEQDKFGK VKFAVLQTYG DTTHTLVEKM NYIGQFLPGY EAPAFMDPLL PKLPKCSLEM
IDHIVGNQPD QEMVSASEWY LKNLQFHRFW SVDDTQVHTE YSSLRSIVVA NYEESIKMPI
NEPAPGKKKS QIQEYVDYNG GAGVQHIALK TEDIITAIRH LRERGLEFLS VPSTYYKQLR
EKLKTAKIKV KENIDALEEL KILVDYDEKG YLLQIFTKPV QDRPTLFLEV IQRHNHQGFG
AGNFNSLFKA FEEEQNLRGN LTNMETNGVV PGM
