Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P32754 (HPPD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
4-hydroxyphenylpyruvate dioxygenase

EC=1.13.11.27
Alternative name(s):
4-hydroxyphenylpyruvic acid oxidase
Short name=4HPPD
Short name=HPD
Short name=HPPDase
Gene names
Name:HPD
Synonyms:PPD
OrganismHomo sapiens (Human) [Reference proteome]
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)

Function

Key enzyme in the degradation of tyrosine.

Catalytic activity

4-hydroxyphenylpyruvate + O2 = homogentisate + CO2.

Cofactor

Binds 1 iron ion per subunit By similarity.

Pathway

Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 3/6.

Subunit structure

Homodimer.

Involvement in disease

Tyrosinemia 3 (TYRSN3) [MIM:276710]: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild mental retardation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12

Hawkinsinuria (HAWK) [MIM:140350]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities

Belongs to the 4HPPD family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P32754-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P32754-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.9
Chain2 – 3933924-hydroxyphenylpyruvate dioxygenase
PRO_0000088388

Sites

Metal binding1831Iron Probable
Metal binding2661Iron Probable
Metal binding3491Iron Probable

Amino acid modifications

Modified residue21N-acetylthreonine Ref.9
Modified residue1321N6-succinyllysine By similarity
Modified residue2111Phosphoserine By similarity
Modified residue2261Phosphoserine By similarity
Modified residue2501Phosphoserine By similarity

Natural variations

Alternative sequence1 – 3939Missing in isoform 2.
VSP_044302
Natural variant331A → T in two patients with hawkinsinuria. Ref.11 Ref.12
Corresponds to variant rs1154510 [ dbSNP | Ensembl ].
VAR_015444
Natural variant1131R → Q.
Corresponds to variant rs11833399 [ dbSNP | Ensembl ].
VAR_048101
Natural variant1601Y → C in TYRSN3. Ref.11
Corresponds to variant rs28934278 [ dbSNP | Ensembl ].
VAR_015445
Natural variant2671I → F. Ref.11
VAR_015446
Natural variant2681A → V in TYRSN3. Ref.12
VAR_015447
Natural variant3351I → M in TYRSN3. Ref.11
VAR_015448
Natural variant3401V → L. Ref.11
Corresponds to variant rs36023382 [ dbSNP | Ensembl ].
VAR_015449

Experimental info

Sequence conflict1621A → P in AAC73008. Ref.3

Secondary structure

............................................................ 393
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 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

Isoform 2 [UniParc].

Checksum: 45F3E405EBD38707
Show »

FASTA35440,497

References

« Hide 'large scale' references
[1]"Structure of the human 4-hydroxyphenylpyruvic acid dioxygenase gene (HPD)."
Awata H., Endo F., Matsuda I.
Genomics 23:534-539(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[2]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Human 4-hydroxyphenylpyruvate dioxygenase gene (HPD)."
Ruetschi U., Rymo L., Lindstedt S.
Genomics 44:292-299(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Liver and Testis.
[5]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Liver.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[10]"Crystal structure of human 4-hydroxyphenylpyruvate dioxygenase."
Structural genomics consortium (SGC)
Submitted (SEP-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 8-393 IN COMPLEX WITH COBALT IONS.
[11]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS TYRSN3 CYS-160 AND MET-335, VARIANTS THR-33; PHE-267 AND LEU-340.
[12]"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] [Europe PMC] [Abstract]
Cited for: VARIANT TYRSN3 VAL-268, VARIANT HAWK THR-33.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D31628 Genomic DNA. Translation: BAA06498.1.
X72389 mRNA. Translation: CAA51082.1.
U29895 Genomic DNA. Translation: AAC73008.1.
AK057510 mRNA. Translation: BAG51925.1.
AK290826 mRNA. Translation: BAF83515.1.
AC069503 Genomic DNA. No translation available.
AC079360 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW98292.1.
BC024287 mRNA. Translation: AAH24287.1.
CCDSCCDS53839.1. [P32754-2]
CCDS9224.1. [P32754-1]
PIRS32458.
RefSeqNP_001165464.1. NM_001171993.1. [P32754-2]
NP_002141.1. NM_002150.2. [P32754-1]
UniGeneHs.2899.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3ISQX-ray1.75A8-393[»]
ProteinModelPortalP32754.
SMRP32754. Positions 9-384.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109482. 5 interactions.
IntActP32754. 4 interactions.
STRING9606.ENSP00000289004.

Chemistry

ChEMBLCHEMBL1861.
DrugBankDB00348. Nitisinone.

PTM databases

PhosphoSiteP32754.

Polymorphism databases

DMDM417144.

Proteomic databases

MaxQBP32754.
PaxDbP32754.
PRIDEP32754.

Protocols and materials databases

DNASU3242.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000543163; ENSP00000441677; ENSG00000158104. [P32754-2]
GeneID3242.
KEGGhsa:3242.
UCSCuc001ubj.3. human. [P32754-1]

Organism-specific databases

CTD3242.
GeneCardsGC12M122277.
HGNCHGNC:5147. HPD.
HPAHPA038321.
HPA038322.
MIM140350. phenotype.
276710. phenotype.
609695. gene.
neXtProtNX_P32754.
Orphanet2118. Hawkinsinuria.
69723. Tyrosinemia type 3.
PharmGKBPA29420.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3185.
HOGENOMHOG000188687.
HOVERGENHBG005987.
InParanoidP32754.
KOK00457.
OrthoDBEOG75F4D7.
PhylomeDBP32754.

Enzyme and pathway databases

BioCycMetaCyc:HS08267-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00139; UER00362.

Gene expression databases

BgeeP32754.
CleanExHS_HPD.
GenevestigatorP32754.

Family and domain databases

Gene3D3.10.180.10. 2 hits.
InterProIPR005956. 4OHPhenylPyrv_dOase.
IPR029068. Glyas_Bleomycin-R_OHBP_Dase.
IPR004360. Glyas_Fos-R_dOase_dom.
[Graphical view]
PANTHERPTHR11959. PTHR11959. 1 hit.
PfamPF00903. Glyoxalase. 1 hit.
[Graphical view]
PIRSFPIRSF009283. HPP_dOase. 1 hit.
SUPFAMSSF54593. SSF54593. 1 hit.
TIGRFAMsTIGR01263. 4HPPD. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP32754.
GenomeRNAi3242.
NextBio12905.
PROP32754.
SOURCESearch...

Entry information

Entry nameHPPD_HUMAN
AccessionPrimary (citable) accession number: P32754
Secondary accession number(s): A8K461, B3KQ63, Q13234
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

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