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Identification
HMDB Protein ID HMDBP00841
Secondary Accession Numbers
  • 6122
  • HMDBP05699
Name 4-hydroxyphenylpyruvate dioxygenase
Synonyms
  1. 4-hydroxyphenylpyruvic acid oxidase
  2. 4HPPD
  3. HPD
  4. HPPDase
Gene Name HPD
Protein Type Unknown
Biological Properties
General Function Involved in 4-hydroxyphenylpyruvate dioxygenase activity
Specific Function Key enzyme in the degradation of tyrosine.
Pathways
  • Alkaptonuria
  • Disulfiram Action Pathway
  • Dopamine beta-hydroxylase deficiency
  • Hawkinsinuria
  • L-phenylalanine degradation
  • Monoamine oxidase-a deficiency (MAO-A)
  • Phenylalanine and Tyrosine Metabolism
  • Phenylalanine metabolism
  • Phenylketonuria
  • Tyrosine Metabolism
  • Tyrosine metabolism
  • Tyrosinemia Type 2 (or Richner-Hanhart syndrome)
  • Tyrosinemia Type 3 (TYRO3)
  • Tyrosinemia Type I
  • Tyrosinemia, transient, of the newborn
  • Ubiquinone and other terpenoid-quinone biosynthesis
Reactions
4-Hydroxyphenylpyruvic acid + Oxygen → Homogentisic acid + CO(2) details
Phenylpyruvic acid + Oxygen → Ortho-Hydroxyphenylacetic acid + Carbon dioxide details
4-Hydroxyphenylpyruvic acid + Oxygen → Homogentisic acid + Carbon dioxide details
GO Classification
Biological Process
cellular nitrogen compound metabolic process
L-phenylalanine catabolic process
tyrosine catabolic process
Cellular Component
endoplasmic reticulum membrane
cytosol
Golgi membrane
Function
catalytic activity
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
oxidoreductase activity
4-hydroxyphenylpyruvate dioxygenase activity
Molecular Function
metal ion binding
4-hydroxyphenylpyruvate dioxygenase activity
Process
metabolic process
cellular metabolic process
cellular amino acid and derivative metabolic process
cellular amino acid metabolic process
aromatic amino acid family metabolic process
Cellular Location Not Available
Gene Properties
Chromosome Location 12
Locus 12q24-qter
SNPs HPD
Gene Sequence
>1182 bp
ATGACGACTTACAGTGACAAAGGGGCAAAGCCTGAGAGAGGCCGATTCCTCCACTTCCAC
TCTGTGACCTTCTGGGTTGGCAACGCCAAGCAGGCCGCGTCATTCTACTGCAGCAAGATG
GGCTTTGAACCTCTAGCCTACAGGGGCCTGGAGACCGGTTCCCGGGAGGTGGTCAGCCAT
GTAATCAAACAAGGGAAGATTGTGTTTGTCCTCTCCTCAGCGCTCAACCCCTGGAACAAA
GAGATGGGCGATCACCTGGTGAAACACGGTGACGGAGTGAAGGACATTGCGTTCGAGGTG
GAAGATTGTGACTACATCGTGCAGAAAGCACGGGAACGGGGCGCCAAAATCATGCGGGAG
CCCTGGGTAGAGCAAGACAAGTTTGGGAAGGTGAAGTTTGCTGTGCTGCAGACGTATGGG
GACACCACACACACCCTGGTGGAGAAGATGAACTACATCGGCCAATTCTTGCCTGGATAT
GAGGCCCCAGCGTTCATGGACCCCCTACTTCCTAAACTGCCCAAATGCAGTCTGGAGATG
ATCGACCACATTGTGGGAAACCAGCCTGATCAGGAGATGGTGTCCGCCTCCGAATGGTAC
CTGAAAAACCTGCAGTTCCACCGCTTCTGGTCCGTGGATGACACGCAGGTGCACACGGAA
TATAGCTCTCTGCGATCCATTGTGGTGGCCAACTATGAAGAGTCCATCAAGATGCCCATC
AATGAGCCAGCGCCTGGCAAGAAGAAGTCCCAGATCCAGGAATATGTGGACTATAACGGG
GGCGCTGGGGTCCAGCACATCGCTCTCAAGACCGAAGACATCATCACAGCGATTCGCCAC
TTGAGAGAGAGAGGCCTGGAGTTCTTATCTGTTCCCTCCACGTACTACAAACAACTGCGG
GAGAAGCTGAAGACGGCCAAGATCAAGGTGAAGGAGAACATTGATGCCCTGGAGGAGCTG
AAAATCCTGGTGGACTACGACGAGAAAGGCTACCTCCTGCAGATCTTCACCAAACCGGTG
CAGGACCGGCCCACGCTCTTCCTGGAAGTCATCCAGCGCCACAACCACCAGGGTTTTGGA
GCCGGCAACTTCAACTCACTGTTCAAGGCTTTCGAGGAGGAGCAGAACCTGCGGGGTAAC
CTCACCAACATGGAGACCAATGGGGTGGTGCCCGGCATGTAA
Protein Properties
Number of Residues 393
Molecular Weight 40497.105
Theoretical pI 6.343
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>4-hydroxyphenylpyruvate dioxygenase
MTTYSDKGAKPERGRFLHFHSVTFWVGNAKQAASFYCSKMGFEPLAYRGLETGSREVVSH
VIKQGKIVFVLSSALNPWNKEMGDHLVKHGDGVKDIAFEVEDCDYIVQKARERGAKIMRE
PWVEQDKFGKVKFAVLQTYGDTTHTLVEKMNYIGQFLPGYEAPAFMDPLLPKLPKCSLEM
IDHIVGNQPDQEMVSASEWYLKNLQFHRFWSVDDTQVHTEYSSLRSIVVANYEESIKMPI
NEPAPGKKKSQIQEYVDYNGGAGVQHIALKTEDIITAIRHLRERGLEFLSVPSTYYKQLR
EKLKTAKIKVKENIDALEELKILVDYDEKGYLLQIFTKPVQDRPTLFLEVIQRHNHQGFG
AGNFNSLFKAFEEEQNLRGNLTNMETNGVVPGM
GenBank ID Protein 288105
UniProtKB/Swiss-Prot ID P32754
UniProtKB/Swiss-Prot Entry Name HPPD_HUMAN
PDB IDs
GenBank Gene ID X72389
GeneCard ID HPD
GenAtlas ID HPD
HGNC ID HGNC:5147
References
General References
  1. 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, 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Ruetschi 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. 1993 May 1;213(3):1081-9. [PubMed:8504803 ]
  4. Awata H, Endo F, Matsuda I: Structure of the human 4-hydroxyphenylpyruvic acid dioxygenase gene (HPD). Genomics. 1994 Oct;23(3):534-9. [PubMed:7851880 ]
  5. Stenman G, Roijer E, Ruetschi 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. 1995;71(4):374-6. [PubMed:8521727 ]
  6. Ruetschi U, Cerone R, Perez-Cerda C, Schiaffino MC, Standing S, Ugarte M, Holme E: Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. Hum Genet. 2000 Jun;106(6):654-62. [PubMed:10942115 ]
  7. Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F: Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. Mol Genet Metab. 2000 Nov;71(3):506-10. [PubMed:11073718 ]