PAH
entrez
5053
canonical
uniprot
P00439
canonical
ensembl
ENSG00000171759
resolver
ensp
ENSP00000448059
resolver
ensp
ENSP00000576752
resolver
ensp
ENSP00000654101
resolver
enst
ENST00000553106
resolver
enst
ENST00000906693
resolver
genesymbol
PAH
resolver
hgnc
HGNC:8582
resolver
uniprot
Q16717
resolver
uniprot
Q8TC14
resolver
uniprot_entry
PH4H_HUMAN
resolver
uniprot_sec
Q16717
resolver
uniprot_sec
Q8TC14
resolver
activity_regulation
ACTIVITY REGULATION: N-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. {ECO:0000269|PubMed:18460651, ECO:0000269|PubMed:18835579}.
uniprot
proteins
amino_acid_sequence
MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEEVGALAKVLRLFEENDVNLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRHDIGATVHELSRDKKKDTVPWFPRTIQELDRFANQILSYGAELDADHPGFKDPVYRARRKQFADIAYNYRHGQPIPRVEYMEEEKKTWGTVFKTLKSLYKTHACYEYNHIFPLLEKYCGFHEDNIPQLEDVSQFLQTCTGFRLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFAQFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLCKQGDSIKAYGAGLLSSFGELQYCLSEKPKLLPLELEKTAIQNYTVTEFQPLYYVAESFNDAKEKVRNFAATIPRPFSVRYDPYTQRIEVLDNTQQLKILADSINSEIGILCSALQKIK
uniprot
proteins
disease_involvement
DISEASE: Phenylalanine hydroxylase deficiency (PAH deficiency) [MIM:261600]: An autosomal recessive inborn error of phenylalanine metabolism characterized by intolerance to dietary intake of the essential amino acid phenylalanine. The disease spectrum depends on the degree of PAH deficiency and the phenylalanine levels in plasma. Severe deficiency causes classic phenylketonuria (PKU) that is characterized by plasma concentrations of phenylalanine persistently above 1200 umol/L. PKU patients develop profound and irreversible intellectual disability, 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. Less severe forms of PAH deficiency are characterized by phenylalanine levels above normal (120 umol/L) but below 1200 umol/L and include moderate PKU, mild PKU, non-PKU hyperphenylalaninemia (non-PKU HPA) and mild hyperphenylalaninemia. Individuals with PAH deficiency who have plasma phenylalanine concentrations consistently below 600 umol/L on an unrestricted diet are not at higher risk of developing intellectual, neurologic, and neuropsychological impairment than are individuals without PAH deficiency. {ECO:0000269|PubMed:10200057, ECO:0000269|PubMed:10679941, ECO:0000269|PubMed:11180595, ECO:0000269|PubMed:11326337, ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:11461196, ECO:0000269|PubMed:11935335, ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1301187, ECO:0000269|PubMed:1355066, ECO:0000269|PubMed:1358789, 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:18538294, 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:32668217, ECO:0000269|PubMed:7833954, ECO:0000269|PubMed:8068076, ECO:0000269|PubMed:8088845, ECO:0000269|PubMed:8098245, ECO:0000269|PubMed:8406445, ECO:0000269|PubMed:8889583, ECO:0000269|PubMed:8889590, ECO:0000269|PubMed:9048935, ECO:0000269|PubMed:9101291, ECO:0000269|PubMed:9450897, ECO:0000269|PubMed:9452061, ECO:0000269|PubMed:9452062, ECO:0000269|PubMed:9521426, ECO:0000269|PubMed:9600453, ECO:0000269|PubMed:9634518, ECO:0000269|PubMed:9792407, ECO:0000269|PubMed:9792411, ECO:0000269|PubMed:9852673, ECO:0000269|PubMed:9950317}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.14.16.1
uniprot
proteins
function
FUNCTION: Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine. {ECO:0000269|PubMed:18460651, ECO:0000269|PubMed:18835579}.
uniprot
proteins
mass_dalton
51862
uniprot
proteins
mutagenesis
MUTAGEN 283; /note="I->C: Loss of positive cooperativity and reduction of fold-activation by L-Phe preincubation."; /evidence="ECO:0000269|PubMed:18835579
uniprot
proteins
pathway_participation
PATHWAY: Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 1/6.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine. {ECO:0000269|PubMed:12185072}.
uniprot
proteins
protein_family
Biopterin-dependent aromatic amino acid hydroxylase family
uniprot
proteins
pubmed
10200057
uniprot
proteins
pubmed
10679941
uniprot
proteins
pubmed
10694386
uniprot
proteins
pubmed
11180595
uniprot
proteins
pubmed
11326337
uniprot
proteins
pubmed
11385716
uniprot
proteins
pubmed
11461196
uniprot
proteins
pubmed
11718561
uniprot
proteins
pubmed
11935335
uniprot
proteins
pubmed
12185072
uniprot
proteins
pubmed
12501224
uniprot
proteins
pubmed
1301187
uniprot
proteins
pubmed
1355066
uniprot
proteins
pubmed
1358789
uniprot
proteins
pubmed
1363837
uniprot
proteins
pubmed
1363838
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1671810
uniprot
proteins
pubmed
1672290
uniprot
proteins
pubmed
1672294
uniprot
proteins
pubmed
1679029
uniprot
proteins
pubmed
1679030
uniprot
proteins
pubmed
1709636
uniprot
proteins
pubmed
18460651
uniprot
proteins
pubmed
18538294
uniprot
proteins
pubmed
18835579
uniprot
proteins
pubmed
1975559
uniprot
proteins
pubmed
2014802
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
2246858
uniprot
proteins
pubmed
22513348
uniprot
proteins
pubmed
22526846
uniprot
proteins
pubmed
23792259
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
2461704
uniprot
proteins
pubmed
2564729
uniprot
proteins
pubmed
2615649
uniprot
proteins
pubmed
2840952
uniprot
proteins
pubmed
2986678
uniprot
proteins
pubmed
32668217
uniprot
proteins
pubmed
7833954
uniprot
proteins
pubmed
8068076
uniprot
proteins
pubmed
8088845
uniprot
proteins
pubmed
8098245
uniprot
proteins
pubmed
8364546
uniprot
proteins
pubmed
8406445
uniprot
proteins
pubmed
8594560
uniprot
proteins
pubmed
8889583
uniprot
proteins
pubmed
8889590
uniprot
proteins
pubmed
9048935
uniprot
proteins
pubmed
9101291
uniprot
proteins
pubmed
9406548
uniprot
proteins
pubmed
9450897
uniprot
proteins
pubmed
9452061
uniprot
proteins
pubmed
9452062
uniprot
proteins
pubmed
9521426
uniprot
proteins
pubmed
9600453
uniprot
proteins
pubmed
9634518
uniprot
proteins
pubmed
9642259
uniprot
proteins
pubmed
9792407
uniprot
proteins
pubmed
9792411
uniprot
proteins
pubmed
9843368
uniprot
proteins
pubmed
9852673
uniprot
proteins
pubmed
9950317
uniprot
proteins
sequence_length
452
uniprot
proteins