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Showing Protein Phenylalanine-4-hydroxylase (HMDBP00280)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 11 metabolites
Identification
HMDB Protein ID HMDBP00280
Secondary Accession Numbers
  • 5512
  • HMDBP05339
Name Phenylalanine-4-hydroxylase
Synonyms
  1. PAH
  2. Phe-4-monooxygenase
Gene Name PAH
Protein Type Enzyme
Biological Properties
General Function Involved in amino acid binding
Specific Function Not Available
Pathways
  • L-phenylalanine degradation
  • Phenylalanine and Tyrosine Metabolism
  • Phenylalanine metabolism
  • Phenylalanine, tyrosine and tryptophan biosynthesis
  • Phenylketonuria
  • Tyrosinemia Type 2 (or Richner-Hanhart syndrome)
  • Tyrosinemia Type 3 (TYRO3)
Reactions
L-Phenylalanine + Tetrahydrobiopterin + Oxygen → L-Tyrosine + 4a-Hydroxytetrahydrobiopterin details
Tetrahydrobiopterin + L-Phenylalanine + Oxygen → 4a-Carbinolamine tetrahydrobiopterin + L-Tyrosine + Water details
GO Classification
Biological Process
protein hydroxylation
cellular nitrogen compound metabolic process
tetrahydrobiopterin metabolic process
tyrosine biosynthetic process
neurotransmitter biosynthetic process
cellular amino acid biosynthetic process
L-phenylalanine catabolic process
catecholamine biosynthetic process
Cellular Component
cytosol
Function
ion binding
cation binding
metal ion binding
phenylalanine 4-monooxygenase activity
binding
catalytic activity
transition metal ion binding
iron ion binding
monooxygenase activity
carboxylic acid binding
amino acid binding
oxidoreductase activity
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen
Molecular Function
phenylalanine 4-monooxygenase activity
cofactor binding
iron ion binding
amino acid binding
Process
l-phenylalanine metabolic process
l-phenylalanine catabolic process
metabolic process
cellular metabolic process
oxidation reduction
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 12q22-q24.2
SNPs PAH
Gene Sequence 
>1359 bp
ATGTCCACTGCGGTCCTGGAAAACCCAGGCTTGGGCAGGAAACTCTCTGACTTTGGACAG
GAAACAAGCTATATTGAAGACAACTGCAATCAAAATGGTGCCATATCACTGATCTTCTCA
CTCAAAGAAGAAGTTGGTGCATTGGCCAAAGTATTGCGCTTATTTGAGGAGAATGATGTA
AACCTGACCCACATTGAATCTAGACCTTCTCGTTTAAAGAAAGATGAGTATGAATTTTTC
ACCCATTTGGATAAACGTAGCCTGCCTGCTCTGACAAACATCATCAAGATCTTGAGGCAT
GACATTGGTGCCACTGTCCATGAGCTTTCACGAGATAAGAAGAAAGACACAGTGCCCTGG
TTCCCAAGAACCATTCAAGAGCTGGACAGATTTGCCAATCAGATTCTCAGCTATGGAGCG
GAACTGGATGCTGACCACCCTGGTTTTAAAGATCCTGTGTACCGTGCAAGACGGAAGCAG
TTTGCTGACATTGCCTACAACTACCGCCATGGGCAGCCCATCCCTCGAGTGGAATACATG
GAGGAAGAAAAGAAAACATGGGGCACAGTGTTCAAGACTCTGAAGTCCTTGTATAAAACC
CATGCTTGCTATGAGTACAATCACATTTTTCCACTTCTTGAAAAGTACTGTGGCTTCCAT
GAAGATAACATTCCCCAGCTGGAAGACGTTTCTCAATTCCTGCAGACTTGCACTGGTTTC
CGCCTCCGACCTGTGGCTGGCCTGCTTTCCTCTCGGGATTTCTTGGGTGGCCTGGCCTTC
CGAGTCTTCCACTGCACACAGTACATCAGACATGGATCCAAGCCCATGTATACCCCCGAA
CCTGACATCTGCCATGAGCTGTTGGGACATGTGCCCTTGTTTTCAGATCGCAGCTTTGCC
CAGTTTTCCCAGGAAATTGGCCTTGCCTCTCTGGGTGCACCTGATGAATACATTGAAAAG
CTCGCCACAATTTACTGGTTTACTGTGGAGTTTGGGCTCTGCAAACAAGGAGACTCCATA
AAGGCATATGGTGCTGGGCTCCTGTCATCCTTTGGTGAATTACAGTACTGCTTATCAGAG
AAGCCAAAGCTTCTCCCCCTGGAGCTGGAGAAGACAGCCATCCAAAATTACACTGTCACG
GAGTTCCAGCCCCTGTATTACGTGGCAGAGAGTTTTAATGATGCCAAGGAGAAAGTAAGG
AACTTTGCTGCCACAATACCTCGGCCCTTCTCAGTTCGCTACGACCCATACACCCAAAGG
ATTGAGGTCTTGGACAATACCCAGCAGCTTAAGATTTTGGCTGATTCCATTAACAGTGAA
ATTGGAATCCTTTGCAGTGCCCTCCAGAAAATAAAGTAA
Protein Properties
Number of Residues 452
Molecular Weight 51861.565
Theoretical pI 6.595
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence 
>Phenylalanine-4-hydroxylase
MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEEVGALAKVLRLFEENDV
NLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRHDIGATVHELSRDKKKDTVPW
FPRTIQELDRFANQILSYGAELDADHPGFKDPVYRARRKQFADIAYNYRHGQPIPRVEYM
EEEKKTWGTVFKTLKSLYKTHACYEYNHIFPLLEKYCGFHEDNIPQLEDVSQFLQTCTGF
RLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFA
QFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLCKQGDSIKAYGAGLLSSFGELQYCLSE
KPKLLPLELEKTAIQNYTVTEFQPLYYVAESFNDAKEKVRNFAATIPRPFSVRYDPYTQR
IEVLDNTQQLKILADSINSEIGILCSALQKIK
GenBank ID Protein 189937
UniProtKB/Swiss-Prot ID P00439
UniProtKB/Swiss-Prot Entry Name PH4H_HUMAN
PDB IDs
GenBank Gene ID K03020
GeneCard ID PAH
GenAtlas ID PAH
HGNC ID HGNC:8582
References
General References
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  8. Erlandsen H, Bjorgo E, Flatmark T, Stevens RC: Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase. Biochemistry. 2000 Mar 7;39(9):2208-17. [PubMed:10694386 ]
  9. Andersen OA, Flatmark T, Hough E: High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J Mol Biol. 2001 Nov 23;314(2):279-91. [PubMed:11718561 ]
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  20. Okano Y, Wang T, Eisensmith RC, Longhi R, Riva E, Giovannini M, Cerone R, Romano C, Woo SL: Phenylketonuria missense mutations in the Mediterranean. Genomics. 1991 Jan;9(1):96-103. [PubMed:1672294 ]
  21. Dworniczak B, Grudda K, Stumper J, Bartholome K, Aulehla-Scholz C, Horst J: Phenylalanine hydroxylase gene: novel missense mutation in exon 7 causing severe phenylketonuria. Genomics. 1991 Jan;9(1):193-9. [PubMed:1672290 ]
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  23. Caillaud C, Lyonnet S, Rey F, Melle D, Frebourg T, Berthelon M, Vilarinho L, Vaz Osorio R, Rey J, Munnich A: A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria. J Biol Chem. 1991 May 25;266(15):9351-4. [PubMed:1709636 ]
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