Names & Taxonomy

Uniprot ID:
P00439
Entry Name:
PH4H_HUMAN
Status:
reviewed
Protein Names:
Phenylalanine-4-hydroxylase (PAH) (EC 1.14.16.1) (Phe-4-monooxygenase)
Gene Names:
PAH
Gene Names Primary:
PAH
Organism:
Homo sapiens (Human)

Structure

Length:
452
Sequence:
MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEEVGALAKVLRLFEENDVNLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRHDIGATVHELSRDKKKDTVPWFPRTIQELDRFANQILSYGAELDADHPGFKDPVYRARRKQFADIAYNYRHGQPIPRVEYMEEEKKTWGTVFKTLKSLYKTHACYEYNHIFPLLEKYCGFHEDNIPQLEDVSQFLQTCTGFRLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFAQFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLCKQGDSIKAYGAGLLSSFGELQYCLSEKPKLLPLELEKTAIQNYTVTEFQPLYYVAESFNDAKEKVRNFAATIPRPFSVRYDPYTQRIEVLDNTQQLKILADSINSEIGILCSALQKIK
Proteomes:
UP000005640

Function

Pathway:
Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 1/6.
Catalytic Activity:
L-phenylalanine + tetrahydrobiopterin + O(2) = L-tyrosine + 4a-hydroxytetrahydrobiopterin.
Cofactor:
COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=150 uM for L-Phe with BH(4) as cofactor
Enzyme Regulation:
ENZYME 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.
Cross Reference Drug Bank:
DB06262 DB00668 DB00120 DB00368 DB00360
Gene Ontology Go:
cytosol
extracellular exosome
amino acid binding
cofactor binding
iron ion binding
phenylalanine 4-monooxygenase activity
catecholamine biosynthetic process
cellular amino acid biosynthetic process
cellular nitrogen compound metabolic process
L-phenylalanine catabolic process
neurotransmitter biosynthetic process
protein hydroxylation
small molecule metabolic process
tetrahydrobiopterin metabolic process
tyrosine biosynthetic process
Gene Ontology Biological Process:
catecholamine biosynthetic process
cellular amino acid biosynthetic process
cellular nitrogen compound metabolic process
L-phenylalanine catabolic process
neurotransmitter biosynthetic process
protein hydroxylation
small molecule metabolic process
tetrahydrobiopterin metabolic process
tyrosine biosynthetic process
Gene Ontology Molecular Function:
amino acid binding
cofactor binding
iron ion binding
phenylalanine 4-monooxygenase activity
Gene Ontology Cellular Component:
cytosol
extracellular exosome
Keywords:
3D-structure
Allosteric enzyme
Complete proteome
Direct protein sequencing
Disease mutation
Iron
Metal-binding
Monooxygenase
Oxidoreductase
Phenylalanine catabolism
Phenylketonuria
Phosphoprotein
Polymorphism
Reference proteome

Publication

PubMed ID:
2986678 15489334 2461704 12185072 18835579 21269460 24275569 9406548 9843368 9642259 10694386 11718561 1679029 2246858 1301187 8594560 2840952 2564729 2615649 1975559 1671810 2014802 1672294 1672290 1679030 1709636 1358789 1355066 1363837 1363838 8406445 8098245 8364546 8068076 8088845 7833954 8889583 8889590 9048935 9101291 9450897 9521426 9600453 10200057 9452061 9452062 9792407 9792411 9852673 9950317 10679941 11326337 11180595 11385716 11461196 11935335 12501224 18538294 23792259 22526846 22513348