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MGP002194

UniProt Annotations

Entry Information
Gene Namephenylalanine hydroxylase
Protein EntryPH4H_HUMAN
UniProt IDP00439
SpeciesHuman
Comments
Comment typeDescription
Biophysicochemical PropertiesKinetic parameters: KM=150 uM for L-Phe with BH(4) as cofactor {ECO:0000269|PubMed:18835579}; KM=30 uM for BH(4) {ECO:0000269|PubMed:18835579}; Vmax=3640 nmol/min/mg enzyme with BH(4) as cofactor (preincubated with L-Phe) {ECO:0000269|PubMed:18835579}; Vmax=1230 nmol/min/mg enzyme with BH(4) as cofactor (preincubated with BH(4)) {ECO:0000269|PubMed:18835579}; Temperature dependence: Optimum temperature is 50 degrees Celsius. {ECO:0000269|PubMed:18835579};
Catalytic ActivityL-phenylalanine + tetrahydrobiopterin + O(2) = L-tyrosine + 4a-hydroxytetrahydrobiopterin.
CofactorName=Fe(2+); Xref=ChEBI:CHEBI:29033;
DiseaseHyperphenylalaninemia (HPA) [MIM:261600]: Mildest form of phenylalanine hydroxylase deficiency. {ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:11935335, ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1358789, ECO:0000269|PubMed:23792259, ECO:0000269|PubMed:8088845, ECO:0000269|PubMed:8098245, ECO:0000269|PubMed:9521426, ECO:0000269|PubMed:9852673}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseNon-phenylketonuria hyperphenylalaninemia (Non-PKU HPA) [MIM:261600]: Mild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseasePhenylketonuria (PKU) [MIM:261600]: Autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor. {ECO:0000269|PubMed:10200057, ECO:0000269|PubMed:10679941, ECO:0000269|PubMed:11180595, ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:11461196, ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1355066, ECO:0000269|PubMed:1363837, ECO:0000269|PubMed:1363838, ECO:0000269|PubMed:1671810, ECO:0000269|PubMed:1672290, ECO:0000269|PubMed:1672294, ECO:0000269|PubMed:1679030, ECO:0000269|PubMed:1709636, ECO:0000269|PubMed:1975559, ECO:0000269|PubMed:2014802, ECO:0000269|PubMed:22513348, ECO:0000269|PubMed:22526846, ECO:0000269|PubMed:23792259, ECO:0000269|PubMed:2564729, ECO:0000269|PubMed:2615649, ECO:0000269|PubMed:2840952, ECO:0000269|PubMed:7833954, ECO:0000269|PubMed:8068076, ECO:0000269|PubMed:8406445, ECO:0000269|PubMed:8889590, ECO:0000269|PubMed:9048935, ECO:0000269|PubMed:9101291, ECO:0000269|PubMed:9452061, ECO:0000269|PubMed:9452062, ECO:0000269|PubMed:9521426, ECO:0000269|PubMed:9600453, ECO:0000269|PubMed:9792407, ECO:0000269|PubMed:9950317}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationN-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an "inhibitory" domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule.
PathwayAmino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 1/6.
PolymorphismThe Glu-274 variant occurs on approximately 4% of African-American PAH alleles. The enzyme activity of the variant protein is indistinguishable from that of the wild-type form.
PtmPhosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine. {ECO:0000269|PubMed:12185072}.
SimilarityBelongs to the biopterin-dependent aromatic amino acid hydroxylase family. {ECO:0000305}.
SimilarityContains 1 ACT domain. {ECO:0000255|PROSITE- ProRule:PRU01007}.
SubunitHomodimer and homotetramer. {ECO:0000269|PubMed:9642259}.
Web ResourceName=PAHdb; Note=Phenylalanine hydroxylase locus knowledgebase; URL="http://www.pahdb.mcgill.ca/";
Web ResourceName=Wikipedia; Note=Phenylalanine hydroxylase entry; URL="http://en.wikipedia.org/wiki/Phenylalanine_hydroxylase";
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