Reviewed, UniProtKB/Swiss-Prot P32754 (HPPD_HUMAN)

Names and origin

Protein names

Recommended name:
    4-hydroxyphenylpyruvate dioxygenase
    EC=1.13.11.27
Alternative name(s):
    4-hydroxyphenylpyruvic acid oxidase
      Short name=HPPDase
      Short name=4HPPD
      Short name=HPD

Gene names

Name:	HPD
Synonyms:	PPD

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	393 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (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 structure	Homodimer.
Involvement in disease	Defects in HPD are the cause of tyrosinemia type 3 (TYRO3) [MIM:276710]. TYRO3 is an inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild mental retardation. Ref.5 Ref.6 Defects in HPD are a cause of hawkinsinuria (HAWK) [MIM:140350]. HAWK is an inborn error of tyrosine metabolism characterized by failure to thrive, persistent metabolic acidosis, fine and sparse hair, and excretion of the unusual cyclic amino acid metabolite, hawkinsin, in the urine. Ref.6
Sequence similarities	Belongs to the 4HPPD family.

Ontologies

Keywords
Biological process	Phenylalanine catabolism Tyrosine catabolism
Coding sequence diversity	Polymorphism
Disease	Disease mutation Mental retardation
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
PTM	Acetylation Phosphoprotein
Gene Ontology (GO)
Biological process	L-phenylalanine catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW tyrosine catabolic process Ref.2 Traceable author statement. Source: ProtInc
Molecular function	4-hydroxyphenylpyruvate dioxygenase activity Inferred from electronic annotation. Source: EC iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 393	392	4-hydroxyphenylpyruvate dioxygenase		PRO_0000088388
Sites
	Metal binding	183	1	Iron By similarity
	Metal binding	266	1	Iron By similarity
	Metal binding	349	1	Iron By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylthreonine By similarity
	Modified residue	250	1	Phosphoserine By similarity
Natural variations
	Natural variant	33	1	A → T in two patients with hawkinsinuria. dbSNP rs1154510. Ref.5 Ref.6		VAR_015444
	Natural variant	113	1	R → Q: dbSNP rs11833399.		VAR_048101
	Natural variant	160	1	Y → C in TYRO3. Ref.5		VAR_015445
	Natural variant	267	1	I → F Ref.5		VAR_015446
	Natural variant	268	1	A → V in TYRO3. Ref.6		VAR_015447
	Natural variant	335	1	I → M in TYRO3. Ref.5		VAR_015448
	Natural variant	340	1	V → L: dbSNP rs36023382. Ref.5		VAR_015449
Experimental info
	Sequence conflict	162	1	A → P in AAC73008. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P32754-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 4314A16532C33A2F	FASTA	393	44,934
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human 4-hydroxyphenylpyruvate dioxygenase. Primary structure and chromosomal localization of the gene." Rueetschi U., Dellsen A., Sahlin P., Stenman G., Rymo L., Lindstedt S. Eur. J. Biochem. 213:1081-1089(1993) [PubMed: 8504803] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Structure of the human 4-hydroxyphenylpyruvic acid dioxygenase gene (HPD)." Awata H., Endo F., Matsuda I. Genomics 23:534-539(1994) [PubMed: 7851880] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Regional assignment of the human 4-hydroxyphenylpyruvate dioxygenase gene (HPD) to 12q24-->qter by fluorescence in situ hybridization." Stenman G., Roijer E., Rueetschi U., Dellsen A., Rymo L., Lindstedt S. Cytogenet. Cell Genet. 71:374-376(1995) [PubMed: 8521727] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[5]	"Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III." Rueetschi U., Cerone R., Perez-Cerda C., Schiaffino M.C., Standing S., Ugarte M., Holme E. Hum. Genet. 106:654-662(2000) [PubMed: 10942115] [Abstract] Cited for: VARIANTS TYRO3 CYS-160 AND MET-335, VARIANTS THR-33; PHE-267 AND LEU-340.
[6]	"Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria." Tomoeda K., Awata H., Matsuura T., Matsuda I., Ploechl E., Milovac T., Boneh A., Scott C.R., Danks D.M., Endo F. Mol. Genet. Metab. 71:506-510(2000) [PubMed: 11073718] [Abstract] Cited for: VARIANT TYRO3 VAL-268, VARIANT HAWK THR-33.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U29895 Genomic DNA. Translation: AAC73008.1. D31628 Genomic DNA. Translation: BAA06498.1. X72389 mRNA. Translation: CAA51082.1. BC024287 mRNA. Translation: AAH24287.1.
IPI	IPI00218297.
PIR	S32458.
RefSeq	NP_002141.1.
UniGene	Hs.2899
3D structure databases
SMR	P32754. Positions 8-366.
ModBase	Search...
PTM databases
PhosphoSite	P32754.
Proteomic databases
PRIDE	P32754.
Genome annotation databases
Ensembl	ENSG00000158104. Homo sapiens. [Contig view]
GeneID	3242.
KEGG	hsa:3242.
Organism-specific databases
GeneCards	GC12M120740.
H-InvDB	HIX0011091.
HGNC	HGNC:5147. HPD.
MIM	140350. phenotype. 276710. phenotype. 609695. gene.
Orphanet	2118. Hawkinsinuria. 69723. Tyrosinemia, type 3.
PharmGKB	PA29420.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P32754.
HOVERGEN	P32754.
Enzyme and pathway databases
BioCyc	MetaCyc:MON-12030.
BRENDA	1.13.11.27. 247.
Reactome	REACT_13. Metabolism of amino acids.
Gene expression databases
ArrayExpress	P32754.
Bgee	P32754.
CleanEx	HS_HPD.
GermOnline	ENSG00000158104. Homo sapiens.
Family and domain databases
InterPro	IPR005956. 4OHPhenylPyrv_dOase. IPR004360. Glyas_bleo-R_dOase. [Graphical view]
PANTHER	PTHR11959. HPP_dOase. 1 hit.
Pfam	PF00903. Glyoxalase. 2 hits. [Graphical view]
PIRSF	PIRSF009283. HPP_dOase. 1 hit.
TIGRFAMs	TIGR01263. 4HPPD. 1 hit.
ProtoNet	Search...
Other Resources
DrugBank	DB00348. Nitisinone.
NextBio	12905.
SOURCE	Search...

Entry information

Entry name

HPPD_HUMAN

Accession

Primary (citable) accession number: P32754
Secondary accession number(s): Q13234

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)