4-hydroxyphenylpyruvate dioxygenase

Function

Catalyzes the conversion of 4-hydroxyphenylpyruvic acid to homogentisic acid, one of the steps in tyrosine catabolism. In addition may act as a N6-methyltransferase that methylates adenosine residues at the N(6) position of some RNAs.

Classification

Family (Pfam)

PF00903 Glyoxalase

InterPro

4OHPhenylPyrv_dOase, 4OHPhenylPyrv_dOase_C, 4OHPhenylPyrv_dOase_N, Glyas_Bleomycin-R_OHBP_Dase, Glyas_Fos-R_dOase_dom, VOC_core

Functional cluster

RuBisCO & Carbon-Fixation Enzymes

Experimental structures · PDB · 4

• 3ISQ X-ray 1.75A
• 5EC3 X-ray 2.10A
• 8IM2 X-ray 2.81A
• 8IM3 X-ray 2.78A

A predicted model is available from AlphaFold.

Gene Ontology · 9

• GO:0005829 cytosol
• GO:0005789 endoplasmic reticulum membrane
• GO:0070062 extracellular exosome
• GO:0000139 Golgi membrane
• GO:0003868 4-hydroxyphenylpyruvate dioxygenase activity
• GO:0046872 metal ion binding
• GO:0042803 protein homodimerization activity
• GO:0006559 L-phenylalanine catabolic process
• GO:0006572 L-tyrosine catabolic process

Disease associations

• hawkinsinuria MONDO:0007700
• tyrosinemia type III MONDO:0010162

Drugs targeting this protein · 1

• NITISINONE inhibitor

Related proteins · sequence + function similarity

• 4-hydroxyphenylpyruvate dioxygenase 0.99
• 4-hydroxyphenylpyruvate dioxygenase 0.99
• 4-hydroxyphenylpyruvate dioxygenase 0.99
• 4-hydroxyphenylpyruvate dioxygenase a 0.96
• 4-hydroxyphenylpyruvate dioxygenase 0.95
• 4-hydroxyphenylpyruvate dioxygenase 0.92
• 4-hydroxyphenylpyruvate dioxygenase 0.90
• 4-hydroxyphenylpyruvate dioxygenase 0.89
• 4-hydroxyphenylpyruvate dioxygenase 0.89
• 4-hydroxyphenylpyruvate dioxygenase 0.89
• 4-hydroxyphenylpyruvate dioxygenase 0.89
• 4-hydroxyphenylpyruvate dioxygenase 0.88

Co-cited proteins · studied together in the literature

• 4-hydroxyphenylpyruvate dioxygenase 1 shared papers
• 4-hydroxyphenylpyruvate dioxygenase 1 shared papers

Literature · 18 cited papers

• HPD is an m6A Methyltransferase that Protects Colorectal Cancer Cells from Ferroptotic Cell Death by m6A Methylating SLC7A11/GPX4. Adv. Sci. · 2025
• Structure-based discovery of pyrazole-benzothiadiazole hybrid as human HPPD inhibitors. Structure · 2023
• Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase. Biochem. J. · 2021
• Hawkinsinuria in two unrelated Greek newborns: identification of a novel variant, biochemical findings and treatment. J. Pediatr. Endocrinol. Metab. · 2016
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Product analysis and inhibition studies of a causative Asn to Ser variant of 4-hydroxyphenylpyruvate dioxygenase suggest a simple route to the treatment of Hawkinsinuria. Biochemistry · 2010
• Manifestation of hawkinsinuria in a patient compound heterozygous for hawkinsinuria and tyrosinemia III. Mol. Genet. Metab. · 2007
• The finished DNA sequence of human chromosome 12. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• … and 6 more in the literature graph