Phenylalanine-4-hydroxylase

Function

Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine.

Classification

Family (Pfam)

PF01842 ACT, PF00351 Biopterin_H

InterPro

ACT-like_dom_sf, ACT_dom, ArAA_hydroxylase, ArAA_hydroxylase_Fe/CU_BS, ArAA_hydroxylase_sf, Aro-AA_hydroxylase_C_sf, Aromatic-AA_hydroxylase_C, Euk_PheOH_cat, Phe-4-hydroxylase_tetra, Tyrosine_3-monooxygenase-like

Functional cluster

Central Metabolic Enzymes (KARI/Glycolysis)

Experimental structures · PDB · 20

• 1DMW X-ray 2.00A
• 1J8T X-ray 1.70A
• 1J8U X-ray 1.50A
• 1KW0 X-ray 2.50A
• 1LRM X-ray 2.10A
• 1MMK X-ray 2.00A
• 1MMT X-ray 2.00A
• 1PAH X-ray 2.00A
• 1TDW X-ray 2.10A
• 1TG2 X-ray 2.20A
• 2PAH X-ray 3.10A
• 3PAH X-ray 2.00A
• … and 8 more

A predicted model is available from AlphaFold.

Gene Ontology · 7

• GO:0005829 cytosol
• GO:0005506 iron ion binding
• GO:0004505 phenylalanine 4-monooxygenase activity
• GO:0008652 amino acid biosynthetic process
• GO:0042423 catecholamine biosynthetic process
• GO:0006559 L-phenylalanine catabolic process
• GO:0006571 L-tyrosine biosynthetic process

Disease associations

• phenylketonuria MONDO:0009861

Drugs targeting this protein · 1

• SAPROPTERIN DIHYDROCHLORIDE activator

Related proteins · sequence + function similarity

• Phenylalanine-4-hydroxylase 0.98
• Phenylalanine-4-hydroxylase 0.98
• Phenylalanine-4-hydroxylase 0.98
• Tryptophan 5-hydroxylase 1 0.94
• Tryptophan 5-hydroxylase 1 0.93
• Tryptophan 5-hydroxylase 1 0.92
• Tryptophan 5-hydroxylase 1 0.91
• Protein henna 0.90
• Tryptophan 5-hydroxylase 1 0.90
• Tryptophan 5-hydroxylase 0.89
• Phenylalanine-4-hydroxylase 0.88
• Phenylalanine-4-hydroxylase 0.88

Co-cited proteins · studied together in the literature

• Phenylalanine-4-hydroxylase 1 shared papers
• Phenylalanine-4-hydroxylase 1 shared papers
• Dual oxidase 1 1 shared papers

Literature · 64 cited papers

• The Genetic Landscape and Epidemiology of Phenylketonuria. Am. J. Hum. Genet. · 2020
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Mutation analysis in Hyperphenylalaninemia patients from South Italy. Clin. Biochem. · 2013
• Prevalence of tetrahydrobiopterine (BH4)-responsive alleles among Austrian patients with PAH deficiency: comprehensive results from molecular analysis in 147 patients. J. Inherit. Metab. Dis. · 2013
• Five novel mutations and two large deletions in a population analysis of the phenylalanine hydroxylase gene. Mol. Genet. Metab. · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• The phylogeny of the aromatic amino acid hydroxylases revisited by characterizing phenylalanine hydroxylase from Dictyostelium discoideum. Gene · 2008
• Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability. Am. J. Hum. Genet. · 2008
• Anabolic function of phenylalanine hydroxylase in Caenorhabditis elegans. FASEB J. · 2008
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. N. Engl. J. Med. · 2002
• Phosphorylation and mutations of Ser(16) in human phenylalanine hydroxylase. Kinetic and structural effects. J. Biol. Chem. · 2002
• … and 52 more in the literature graph