Reviewed, UniProtKB/Swiss-Prot P16331 (PH4H_MOUSE)

Names and origin

Protein names

Recommended name:
    Phenylalanine-4-hydroxylase
      Short name=PAH
    EC=1.14.16.1
Alternative name(s):
    Phe-4-monooxygenase

Gene names

Name:

Pah

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	453 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin.
Cofactor	Fe2+ ion.
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.
Pathway	Amino-acid degradation; L-phenylalanine degradation; acetoacetic acid and fumarate from L-phenylalanine: step 1/6.
Subunit structure	Homodimer.
Involvement in disease	Mouse strains deficient in phenylalanine hydroxylase (Pah) were created as models of phenylketonuria (PKU).
Sequence similarities	Belongs to the biopterin-dependent aromatic amino acid hydroxylase family. Contains 1 ACT domain.

Ontologies

Keywords
Biological process	Phenylalanine catabolism
Disease	Disease mutation
Ligand	Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Allosteric enzyme Direct protein sequencing
Gene Ontology (GO)
Biological process	L-phenylalanine catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	amino acid binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW phenylalanine 4-monooxygenase activity Inferred from mutant phenotype. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.2
	Chain	2 – 453	452	Phenylalanine-4-hydroxylase		PRO_0000205549
Regions
	Domain	36 – 111	76	ACT
Sites
	Metal binding	285	1	Iron By similarity
	Metal binding	290	1	Iron By similarity
	Metal binding	330	1	Iron By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.2
	Modified residue	16	1	Phosphoserine; by PKA By similarity
Natural variations
	Natural variant	106	1	V → A in PAH-ENU1; mild PKU phenotype. Ref.5
	Natural variant	263	1	F → S in PAH-ENU2; severe PKU phenotype.

Sequences

	Sequence		Length	Mass (Da)
	P16331-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: FA1CD4D0A598E8D9	FASTA	453	51,929
	10 20 30 40 50 60 MAAVVLENGV LSRKLSDFGQ ETSYIEDNSN QNGAVSLIFS LKEEVGALAK VLRLFEENEI 70 80 90 100 110 120 NLTHIESRPS RLNKDEYEFF TYLDKRSKPV LGSIIKSLRN DIGATVHELS RDKEKNTVPW 130 140 150 160 170 180 FPRTIQELDR FANQILSYGA ELDADHPGFK DPVYRARRKQ FADIAYNYRH GQPIPRVEYT 190 200 210 220 230 240 EEERKTWGTV FRTLKALYKT HACYEHNHIF PLLEKYCGFR EDNIPQLEDV SQFLQTCTGF 250 260 270 280 290 300 RLRPVAGLLS SRDFLGGLAF RVFHCTQYIR HGSKPMYTPE PDICHELLGH VPLFSDRSFA 310 320 330 340 350 360 QFSQEIGLAS LGAPDEYIEK LATIYWFTVE FGLCKEGDSI KAYGAGLLSS FGELQYCLSD 370 380 390 400 410 420 KPKLLPLELE KTACQEYTVT EFRPLYYVAE SFNDAKEKVR TFAATIPRPF SVRYDPYTQR 430 440 450 VEVLDNTQQL KNLADSINSE VGILCHALQK IKS

References

[1]	"Mouse phenylalanine hydroxylase. Homology and divergence from human phenylalanine hydroxylase." Ledley F.D., Grenett H.E., Dunbar B.S., Woo S.L.C. Biochem. J. 267:399-406(1990) [PubMed: 2334400] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6J. Tissue: Liver.
[2]	Bienvenut W.V. Submitted (JUL-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-13; 54-68; 160-169 AND 253-261, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Liver.
[3]	"Amino acid sequence at the phosphorylated site of rat liver phenylalanine hydroxylase and phosphorylation of a corresponding synthetic peptide." Wretborn M., Humble E., Ragnarsson U., Engstrom L. Biochem. Biophys. Res. Commun. 93:403-408(1980) [PubMed: 7387651] [Abstract] Cited for: PROTEIN SEQUENCE OF 12-21.
[4]	"Sequence comparison of rat liver phenylalanine hydroxylase and its cDNA clones." Robson K.J.H., Beattie W., James R.J., Cotton R.C.H., Morgan F.J., Woo S.L.C. Biochemistry 23:5671-5675(1984) [PubMed: 6098294] [Abstract] Cited for: PROTEIN SEQUENCE OF 277-294.
[5]	"Characterization of mutations at the mouse phenylalanine hydroxylase locus." McDonald J.D., Charlton C.K. Genomics 39:402-405(1997) [PubMed: 9119379] [Abstract] Cited for: VARIANTS PAH-ENU1 ALA-106 AND PAH-ENU2 SER-263.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X51942 mRNA. Translation: CAA36205.1.
IPI	IPI00133549.
PIR	S15758.
UniGene	Mm.263539
3D structure databases
HSSP	HSSP built from PDB template 2PAH based on UniProtKB P00439.
SMR	P16331. Positions 18-426, 19-427.
ModBase	Search...
PTM databases
PhosphoSite	P16331.
Proteomic databases
PRIDE	P16331.
Genome annotation databases
Ensembl	ENSMUSG00000020051. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:97473. Pah.
Phylogenomic databases
HOGENOM	P16331.
HOVERGEN	P16331.
Enzyme and pathway databases
BRENDA	1.14.16.1. 244.
Gene expression databases
ArrayExpress	P16331.
Bgee	P16331.
CleanEx	MM_PAH.
GermOnline	ENSMUSG00000020051. Mus musculus.
Family and domain databases
InterPro	IPR002912. ACT_bd. IPR001273. ArAA_hydroxylase. IPR018301. ArAA_hydroxylase_Fe/CU_BS. IPR019774. Aromatic-AA_hydroxylase_C. IPR005961. Phe-4-hydroxylase_tetra. IPR019773. Tyrosine_3-monooxygenase-like. [Graphical view]
Gene3D	G3DSA:1.10.800.10. Aaa_hydroxylase. 1 hit.
PANTHER	PTHR11473. Aaa_hydroxylase. 1 hit.
Pfam	PF01842. ACT. 1 hit. PF00351. Biopterin_H. 1 hit. [Graphical view]
PIRSF	PIRSF000336. TH. 1 hit.
PRINTS	PR00372. FYWHYDRXLASE.
ProDom	PD002559. Aaa_hydroxylase. 1 hit. [Graphical view] [Entries sharing at least one domain]
TIGRFAMs	TIGR01268. Phe4hydrox_tetr. 1 hit.
PROSITE	PS00367. BIOPTERIN_HYDROXYL. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

PH4H_MOUSE

Accession

Primary (citable) accession number: P16331

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 95 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)