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Reviewed, UniProtKB/Swiss-Prot P32754 (HPPD_HUMAN)

Last modified June 16, 2009. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length393 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 3933924-hydroxyphenylpyruvate dioxygenase
PRO_0000088388

Sites

Metal binding1831Iron By similarity
Metal binding2661Iron By similarity
Metal binding3491Iron By similarity

Amino acid modifications

Modified residue21N-acetylthreonine By similarity
Modified residue2501Phosphoserine By similarity

Natural variations

Natural variant331A → T in two patients with hawkinsinuria. dbSNP rs1154510. Ref.5 Ref.6
VAR_015444
Natural variant1131R → Q: dbSNP rs11833399.
VAR_048101
Natural variant1601Y → C in TYRO3. Ref.5
VAR_015445
Natural variant2671I → F Ref.5
VAR_015446
Natural variant2681A → V in TYRO3. Ref.6
VAR_015447
Natural variant3351I → M in TYRO3. Ref.5
VAR_015448
Natural variant3401V → L: dbSNP rs36023382. Ref.5
VAR_015449

Experimental info

Sequence conflict1621A → P in AAC73008. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P32754-1 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 4314A16532C33A2F

FASTA39344,934
        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 

« Hide

References

« Hide '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

Cross-references

Sequence databases

U29895 Genomic DNA. Translation: AAC73008.1.
D31628 Genomic DNA. Translation: BAA06498.1.
X72389 mRNA. Translation: CAA51082.1.
BC024287 mRNA. Translation: AAH24287.1.
IPIIPI00218297.
PIRS32458.
RefSeqNP_002141.1.
UniGeneHs.2899

3D structure databases

SMRP32754. Positions 8-366.
ModBaseSearch...

PTM databases

PhosphoSiteP32754.

Proteomic databases

PRIDEP32754.

Genome annotation databases

EnsemblENSG00000158104. Homo sapiens. [Contig view]
GeneID3242.
KEGGhsa:3242.

Organism-specific databases

GeneCardsGC12M120740.
H-InvDBHIX0011091.
HGNCHGNC:5147. HPD.
MIM140350. phenotype.
276710. phenotype.
609695. gene.
Orphanet2118. Hawkinsinuria.
69723. Tyrosinemia, type 3.
PharmGKBPA29420.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP32754.
HOVERGENP32754.

Enzyme and pathway databases

BioCycMetaCyc:MON-12030.
BRENDA1.13.11.27. 247.
ReactomeREACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpressP32754.
BgeeP32754.
CleanExHS_HPD.
GermOnlineENSG00000158104. Homo sapiens.

Family and domain databases

InterProIPR005956. 4OHPhenylPyrv_dOase.
IPR004360. Glyas_bleo-R_dOase.
[Graphical view]
PANTHERPTHR11959. HPP_dOase. 1 hit.
PfamPF00903. Glyoxalase. 2 hits.
[Graphical view]
PIRSFPIRSF009283. HPP_dOase. 1 hit.
TIGRFAMsTIGR01263. 4HPPD. 1 hit.
ProtoNetSearch...

Other Resources

DrugBankDB00348. Nitisinone.
NextBio12905.
SOURCESearch...

Entry information

Entry nameHPPD_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents