ID   HPPD_HUMAN              Reviewed;         393 AA.
AC   P32754; Q13234;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   04-NOV-2008, entry version 86.
DE   RecName: Full=4-hydroxyphenylpyruvate dioxygenase;
DE            EC=1.13.11.27;
DE   AltName: Full=4-hydroxyphenylpyruvic acid oxidase;
DE            Short=HPPDase;
DE            Short=4HPPD;
DE            Short=HPD;
GN   Name=HPD; Synonyms=PPD;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=93279307; PubMed=8504803;
RA   Rueetschi U., Dellsen A., Sahlin P., Stenman G., Rymo L.,
RA   Lindstedt S.;
RT   "Human 4-hydroxyphenylpyruvate dioxygenase. Primary structure and
RT   chromosomal localization of the gene.";
RL   Eur. J. Biochem. 213:1081-1089(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=95154822; 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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=96103473; PubMed=8521727;
RA   Stenman G., Roijer E., Rueetschi U., Dellsen A., Rymo L.,
RA   Lindstedt S.;
RT   "Regional assignment of the human 4-hydroxyphenylpyruvate dioxygenase
RT   gene (HPD) to 12q24-->qter by fluorescence in situ hybridization.";
RL   Cytogenet. Cell Genet. 71:374-376(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   VARIANTS TYROSINEMIA TYPE III CYS-160 AND MET-335, AND VARIANTS
RP   THR-33; PHE-267 AND LEU-340.
RX   MEDLINE=20395563; PubMed=10942115; DOI=10.1007/s004390050039;
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   [6]
RP   VARIANT TYROSINEMIA TYPE III VAL-268, AND VARIANT HAWKINSINURIA
RP   THR-33.
RX   MEDLINE=20528790; 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   -!- CATALYTIC ACTIVITY: 4-hydroxyphenylpyruvate + O(2) = homogentisate
CC       + CO(2).
CC   -!- COFACTOR: Binds 1 iron ion per subunit (By similarity).
CC   -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC       acetoacetic acid and fumarate from L-phenylalanine: step 3/6.
CC   -!- SUBUNIT: Homodimer.
CC   -!- DISEASE: Defects in HPD are the cause of tyrosinemia type III
CC       [MIM:276710]. It is an autosomal recessive disorder presenting
CC       with acute intermittent ataxia and mild mental retardation.
CC   -!- DISEASE: Defects in HPD are a cause of hawkinsinuria [MIM:140350].
CC       Hawkinsinuria is an autosomal dominant inborn error of metabolism.
CC       Metabolic acidosis and tyrosinemia are transient and symptoms
CC       improve within the first year of life. Patients continue to
CC       excrete the hawkinsin metabolite in their urine throughout life.
CC   -!- SIMILARITY: Belongs to the 4HPPD family.
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.genetests.org/query?gene=HPD";
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DR   EMBL; U29895; AAC73008.1; -; Genomic_DNA.
DR   EMBL; D31628; BAA06498.1; -; Genomic_DNA.
DR   EMBL; X72389; CAA51082.1; -; mRNA.
DR   EMBL; BC024287; AAH24287.1; -; mRNA.
DR   PIR; S32458; S32458.
DR   RefSeq; NP_002141.1; -.
DR   UniGene; Hs.2899; -.
DR   SMR; P32754; 8-366.
DR   PhosphoSite; P32754; -.
DR   Ensembl; ENSG00000158104; Homo sapiens.
DR   GeneID; 3242; -.
DR   KEGG; hsa:3242; -.
DR   H-InvDB; HIX0011091; -.
DR   HGNC; HGNC:5147; HPD.
DR   MIM; 140350; phenotype.
DR   MIM; 276710; phenotype.
DR   MIM; 609695; gene.
DR   Orphanet; 2118; Hawkinsinuria.
DR   Orphanet; 69723; Tyrosinemia type 3.
DR   PharmGKB; PA29420; -.
DR   HOGENOM; P32754; -.
DR   HOVERGEN; P32754; -.
DR   BioCyc; MetaCyc:MON-12030; -.
DR   Reactome; REACT_13; Metabolism of amino acids.
DR   DrugBank; DB00348; Nitisinone.
DR   NextBio; 12905; -.
DR   ArrayExpress; P32754; -.
DR   CleanEx; HS_HPD; -.
DR   GermOnline; ENSG00000158104; Homo sapiens.
DR   GO; GO:0006572; P:tyrosine catabolic process; TAS:ProtInc.
DR   InterPro; IPR005956; 4OHPhenylPyrv_dOase.
DR   InterPro; IPR004360; Glyas_bleo-R_dOase.
DR   PANTHER; PTHR11959; HPP_dOase; 1.
DR   Pfam; PF00903; Glyoxalase; 2.
DR   PIRSF; PIRSF009283; HPP_dOase; 1.
DR   TIGRFAMs; TIGR01263; 4HPPD; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Dioxygenase; Disease mutation; Iron; Metal-binding;
KW   Oxidoreductase; Phenylalanine catabolism; Phosphoprotein;
KW   Polymorphism; Tyrosine catabolism.
FT   INIT_MET      1      1       Removed (By similarity).
FT   CHAIN         2    393       4-hydroxyphenylpyruvate dioxygenase.
FT                                /FTId=PRO_0000088388.
FT   METAL       183    183       Iron (By similarity).
FT   METAL       266    266       Iron (By similarity).
FT   METAL       349    349       Iron (By similarity).
FT   MOD_RES       2      2       N-acetylthreonine (By similarity).
FT   MOD_RES     250    250       Phosphoserine (By similarity).
FT   VARIANT      33     33       A -> T (in two patients with
FT                                hawkinsinuria; dbSNP:rs1154510).
FT                                /FTId=VAR_015444.
FT   VARIANT     160    160       Y -> C (in tyrosinemia type III).
FT                                /FTId=VAR_015445.
FT   VARIANT     267    267       I -> F.
FT                                /FTId=VAR_015446.
FT   VARIANT     268    268       A -> V (in tyrosinemia type III).
FT                                /FTId=VAR_015447.
FT   VARIANT     335    335       I -> M (in tyrosinemia type III).
FT                                /FTId=VAR_015448.
FT   VARIANT     340    340       V -> L.
FT                                /FTId=VAR_015449.
FT   CONFLICT    162    162       A -> P (in Ref. 3; AAC73008).
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
//