[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. PubMed=8504803 [NCBI, ExPASy, EBI, Israel, Japan] Rueetschi U., Dellsen A., Sahlin P., Stenman G., Rymo L., Lindstedt S.; "Human 4-hydroxyphenylpyruvate dioxygenase. Primary structure and chromosomal localization of the gene."; Eur. J. Biochem. 213:1081-1089(1993).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1006/geno.1994.1540; PubMed=7851880 [NCBI, ExPASy, EBI, Israel, Japan] Awata H., Endo F., Matsuda I.; "Structure of the human 4-hydroxyphenylpyruvic acid dioxygenase gene (HPD)."; Genomics 23:534-539(1994).
[3]	NUCLEOTIDE SEQUENCE [MRNA]. PubMed=8521727 [NCBI, ExPASy, EBI, Israel, Japan] Stenman G., Roijer E., Rueetschi U., Dellsen A., Rymo L., Lindstedt S.; "Regional assignment of the human 4-hydroxyphenylpyruvate dioxygenase gene (HPD) to 12q24-->qter by fluorescence in situ hybridization."; Cytogenet. Cell Genet. 71:374-376(1995).
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Liver; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	VARIANTS TYROSINEMIA TYPE III CYS-160 AND MET-335, AND VARIANTS THR-33; PHE-267 AND LEU-340. DOI=10.1007/s004390050039; PubMed=10942115 [NCBI, ExPASy, EBI, Israel, Japan] Rueetschi U., Cerone R., Perez-Cerda C., Schiaffino M.C., Standing S., Ugarte M., Holme E.; "Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III."; Hum. Genet. 106:654-662(2000).
[6]	VARIANT TYROSINEMIA TYPE III VAL-268, AND VARIANT HAWKINSINURIA THR-33. DOI=10.1006/mgme.2000.3085; PubMed=11073718 [NCBI, ExPASy, EBI, Israel, Japan] Tomoeda K., Awata H., Matsuura T., Matsuda I., Ploechl E., Milovac T., Boneh A., Scott C.R., Danks D.M., Endo F.; "Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria."; Mol. Genet. Metab. 71:506-510(2000).

Comments

CATALYTIC ACTIVITY: 4-hydroxyphenylpyruvate + O₂ = homogentisate + CO₂.
COFACTOR: Binds 1 iron ion per subunit (By similarity).
PATHWAY: Amino-acid degradation; L-phenylalanine degradation; acetoacetic acid and fumarate from L-phenylalanine: step 3/6 .
SUBUNIT: Homodimer.
DISEASE: Defects in HPD are the cause of tyrosinemia type III [MIM:276710]. It is an autosomal recessive disorder presenting with acute intermittent ataxia and mild mental retardation.
DISEASE: Defects in HPD are a cause of hawkinsinuria [MIM:140350]. Hawkinsinuria is an autosomal dominant inborn error of metabolism. Metabolic acidosis and tyrosinemia are transient and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life.
SIMILARITY: Belongs to the 4HPPD family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=HPD";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U29895; AAC73008.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
D31628; BAA06498.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X72389; CAA51082.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC024287; AAH24287.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

S32458; S32458.

NP_002141.1; -.

3D structure databases

P32754; 8-366.

PTM databases

P32754; -.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-12030; -.

Reactome

REACT_13; Metabolism of amino acids.

Organism-specific databases

HIX0011091; -.

HGNC:5147; HPD.

HPD.

140350; phenotype. [NCBI / EBI]
276710; phenotype. [NCBI / EBI]
609695; gene. [NCBI / EBI]

Orphanet

2118; Hawkinsinuria.
69723; Tyrosinemia type 3.

PharmGKB

PA29420; -.

GeneCards

P32754.

Gene expression databases

ArrayExpress

P32754; -.

CleanEx

HS_HPD; -.

GermOnline

ENSG00000158104; Homo sapiens.

Ontologies

GO:0006572;	Biological process: tyrosine catabolic process (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR005956; 4OHPhenylPyrv_dOase.
IPR004360; Glyas_bleo-R_dOase.
Graphical view of domain structure.

PANTHER

PTHR11959; HPP_dOase; 1.

Pfam

PF00903; Glyoxalase; 2.
Pfam graphical view of domain structure.

PIRSF

PIRSF009283; HPP_dOase; 1.

TIGRFAMs

TIGR01263; 4HPPD; 1.

BLOCKS

P32754.

Genome annotation databases

Ensembl

ENSG00000158104; Homo sapiens. [Contig view]

GeneID

3242; -.

KEGG

hsa:3242; -.

Phylogenomic databases

HOGENOM

P32754; -.

HOVERGEN

P32754; -.

Other

DB00348; Nitisinone.

HPD; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Acetylation; Dioxygenase; Disease mutation; Iron; Metal-binding; Oxidoreductase; Phenylalanine catabolism; Phosphoprotein; Polymorphism; Tyrosine catabolism.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`INIT_MET`	`1 1`		`Removed (By similarity).`
`CHAIN`	`2 393`	`392`	`4-hydroxyphenylpyruvate dioxygenase.`	`PRO_0000088388`
`METAL`	`183 183`		`Iron (By similarity).`
`METAL`	`266 266`		`Iron (By similarity).`
`METAL`	`349 349`		`Iron (By similarity).`
`MOD_RES`	`2 2`		`N-acetylthreonine (By similarity).`
`MOD_RES`	`250 250`		`Phosphoserine (By similarity).`
`VARIANT`	`33 33`	`1`	`A -> T (in two patients with hawkinsinuria; dbSNP:rs1154510 [NCBI]).`	`VAR_015444 [3D]`
`VARIANT`	`160 160`	`1`	`Y -> C (in tyrosinemia type III).`	`VAR_015445 [3D]`
`VARIANT`	`267 267`	`1`	`I -> F.`	`VAR_015446 [3D]`
`VARIANT`	`268 268`	`1`	`A -> V (in tyrosinemia type III).`	`VAR_015447 [3D]`
`VARIANT`	`335 335`	`1`	`I -> M (in tyrosinemia type III).`	`VAR_015448 [3D]`
`VARIANT`	`340 340`	`1`	`V -> L.`	`VAR_015449 [3D]`
`CONFLICT`	`162 162`		`A -> P (in Ref. 3; AAC73008).`

Sequence information

Length: 393 AA [This is the length of the unprocessed precursor]

Molecular weight: 44934 Da [This is the MW of the unprocessed precursor]

CRC64: 4314A16532C33A2F [This is a checksum on the sequence]

        10         20         30         40         50         60 
MTTYSDKGAK PERGRFLHFH SVTFWVGNAK QAASFYCSKM GFEPLAYRGL ETGSREVVSH 

        70         80         90        100        110        120 
VIKQGKIVFV LSSALNPWNK EMGDHLVKHG DGVKDIAFEV EDCDYIVQKA RERGAKIMRE 

       130        140        150        160        170        180 
PWVEQDKFGK VKFAVLQTYG DTTHTLVEKM NYIGQFLPGY EAPAFMDPLL PKLPKCSLEM 

       190        200        210        220        230        240 
IDHIVGNQPD QEMVSASEWY LKNLQFHRFW SVDDTQVHTE YSSLRSIVVA NYEESIKMPI 

       250        260        270        280        290        300 
NEPAPGKKKS QIQEYVDYNG GAGVQHIALK TEDIITAIRH LRERGLEFLS VPSTYYKQLR 

       310        320        330        340        350        360 
EKLKTAKIKV KENIDALEEL KILVDYDEKG YLLQIFTKPV QDRPTLFLEV IQRHNHQGFG 

       370        380        390 
AGNFNSLFKA FEEEQNLRGN LTNMETNGVV PGM

P32754 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools