Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Phenylalanine-4-hydroxylase

Gene

Pah

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin.

Cofactori

Enzyme regulationi

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: L-phenylalanine degradation

This protein is involved in step 1 of the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine.
Proteins known to be involved in the 6 steps of the subpathway in this organism are:
  1. Phenylalanine-4-hydroxylase (Pah)
  2. Tyrosine aminotransferase (Tat)
  3. 4-hydroxyphenylpyruvate dioxygenase (Hpd)
  4. Homogentisate 1,2-dioxygenase (Hgd)
  5. Maleylacetoacetate isomerase (Gstz1)
  6. Fumarylacetoacetase (Fah)
This subpathway is part of the pathway L-phenylalanine degradation, which is itself part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine, the pathway L-phenylalanine degradation and in Amino-acid degradation.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi285 – 2851Iron; via tele nitrogenBy similarity
Metal bindingi290 – 2901Iron; via tele nitrogenBy similarity
Metal bindingi330 – 3301IronBy similarity

GO - Molecular functioni

  • amino acid binding Source: InterPro
  • iron ion binding Source: InterPro
  • phenylalanine 4-monooxygenase activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Phenylalanine catabolism

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_336040. Phenylalanine and tyrosine catabolism.
UniPathwayiUPA00139; UER00337.

Names & Taxonomyi

Protein namesi
Recommended name:
Phenylalanine-4-hydroxylase (EC:1.14.16.1)
Short name:
PAH
Alternative name(s):
Phe-4-monooxygenase
Gene namesi
Name:Pah
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:97473. Pah.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Mouse strains deficient in phenylalanine hydroxylase (Pah) were created as models of phenylketonuria (PKU).

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 453452Phenylalanine-4-hydroxylasePRO_0000205549Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei16 – 161Phosphoserine; by PKABy similarity

Post-translational modificationi

Phosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP16331.
PaxDbiP16331.
PRIDEiP16331.

PTM databases

PhosphoSiteiP16331.

Expressioni

Gene expression databases

BgeeiP16331.
CleanExiMM_PAH.
ExpressionAtlasiP16331. baseline and differential.
GenevisibleiP16331. MM.

Interactioni

Subunit structurei

Homodimer and homotetramer.By similarity

Protein-protein interaction databases

IntActiP16331. 3 interactions.
MINTiMINT-1855311.
STRINGi10090.ENSMUSP00000020241.

Structurei

3D structure databases

ProteinModelPortaliP16331.
SMRiP16331. Positions 19-427.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini36 – 11479ACTPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 ACT domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG3186.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP16331.
KOiK00500.
OMAiTITEFQP.
OrthoDBiEOG7KM5T1.
TreeFamiTF313327.

Family and domain databases

Gene3Di1.10.800.10. 1 hit.
InterProiIPR002912. ACT_dom.
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]
PANTHERiPTHR11473. PTHR11473. 1 hit.
PfamiPF01842. ACT. 1 hit.
PF00351. Biopterin_H. 1 hit.
[Graphical view]
PIRSFiPIRSF000336. TH. 1 hit.
PRINTSiPR00372. FYWHYDRXLASE.
SUPFAMiSSF56534. SSF56534. 1 hit.
TIGRFAMsiTIGR01268. Phe4hydrox_tetr. 1 hit.
PROSITEiPS51671. ACT. 1 hit.
PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P16331-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAVVLENGV LSRKLSDFGQ ETSYIEDNSN QNGAVSLIFS LKEEVGALAK
60 70 80 90 100
VLRLFEENEI NLTHIESRPS RLNKDEYEFF TYLDKRSKPV LGSIIKSLRN
110 120 130 140 150
DIGATVHELS RDKEKNTVPW FPRTIQELDR FANQILSYGA ELDADHPGFK
160 170 180 190 200
DPVYRARRKQ FADIAYNYRH GQPIPRVEYT EEERKTWGTV FRTLKALYKT
210 220 230 240 250
HACYEHNHIF PLLEKYCGFR EDNIPQLEDV SQFLQTCTGF RLRPVAGLLS
260 270 280 290 300
SRDFLGGLAF RVFHCTQYIR HGSKPMYTPE PDICHELLGH VPLFSDRSFA
310 320 330 340 350
QFSQEIGLAS LGAPDEYIEK LATIYWFTVE FGLCKEGDSI KAYGAGLLSS
360 370 380 390 400
FGELQYCLSD KPKLLPLELE KTACQEYTVT EFQPLYYVAE SFNDAKEKVR
410 420 430 440 450
TFAATIPRPF SVRYDPYTQR VEVLDNTQQL KILADSINSE VGILCHALQK

IKS
Length:453
Mass (Da):51,900
Last modified:July 27, 2011 - v4
Checksum:i551F181FA59DEA5B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti383 – 3831Q → R in CAA36205 (PubMed:2334400).Curated
Sequence conflicti432 – 4321I → N in CAA36205 (PubMed:2334400).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti106 – 1061V → A in PAH-ENU1; mild PKU phenotype. 1 Publication
Natural varianti263 – 2631F → S in PAH-ENU2; severe PKU phenotype. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51942 mRNA. Translation: CAA36205.1.
AC122360 Genomic DNA. No translation available.
BC013458 mRNA. Translation: AAH13458.1.
CCDSiCCDS24102.1.
PIRiS15758.
RefSeqiNP_032803.2. NM_008777.3.
UniGeneiMm.263539.

Genome annotation databases

EnsembliENSMUST00000020241; ENSMUSP00000020241; ENSMUSG00000020051.
GeneIDi18478.
KEGGimmu:18478.
UCSCiuc007gqt.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51942 mRNA. Translation: CAA36205.1.
AC122360 Genomic DNA. No translation available.
BC013458 mRNA. Translation: AAH13458.1.
CCDSiCCDS24102.1.
PIRiS15758.
RefSeqiNP_032803.2. NM_008777.3.
UniGeneiMm.263539.

3D structure databases

ProteinModelPortaliP16331.
SMRiP16331. Positions 19-427.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP16331. 3 interactions.
MINTiMINT-1855311.
STRINGi10090.ENSMUSP00000020241.

PTM databases

PhosphoSiteiP16331.

Proteomic databases

MaxQBiP16331.
PaxDbiP16331.
PRIDEiP16331.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020241; ENSMUSP00000020241; ENSMUSG00000020051.
GeneIDi18478.
KEGGimmu:18478.
UCSCiuc007gqt.2. mouse.

Organism-specific databases

CTDi5053.
MGIiMGI:97473. Pah.

Phylogenomic databases

eggNOGiCOG3186.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP16331.
KOiK00500.
OMAiTITEFQP.
OrthoDBiEOG7KM5T1.
TreeFamiTF313327.

Enzyme and pathway databases

UniPathwayiUPA00139; UER00337.
ReactomeiREACT_336040. Phenylalanine and tyrosine catabolism.

Miscellaneous databases

ChiTaRSiPah. mouse.
NextBioi294182.
PROiP16331.
SOURCEiSearch...

Gene expression databases

BgeeiP16331.
CleanExiMM_PAH.
ExpressionAtlasiP16331. baseline and differential.
GenevisibleiP16331. MM.

Family and domain databases

Gene3Di1.10.800.10. 1 hit.
InterProiIPR002912. ACT_dom.
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]
PANTHERiPTHR11473. PTHR11473. 1 hit.
PfamiPF01842. ACT. 1 hit.
PF00351. Biopterin_H. 1 hit.
[Graphical view]
PIRSFiPIRSF000336. TH. 1 hit.
PRINTSiPR00372. FYWHYDRXLASE.
SUPFAMiSSF56534. SSF56534. 1 hit.
TIGRFAMsiTIGR01268. Phe4hydrox_tetr. 1 hit.
PROSITEiPS51671. ACT. 1 hit.
PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
    Tissue: Liver.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Kidney.
  4. 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, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: C57BL/6.
    Tissue: Liver.
  5. "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] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 12-21.
  6. "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] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 277-294.
  7. "Characterization of mutations at the mouse phenylalanine hydroxylase locus."
    McDonald J.D., Charlton C.K.
    Genomics 39:402-405(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PAH-ENU1 ALA-106 AND PAH-ENU2 SER-263.

Entry informationi

Entry nameiPH4H_MOUSE
AccessioniPrimary (citable) accession number: P16331
Secondary accession number(s): Q91WV1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: July 27, 2011
Last modified: June 24, 2015
This is version 153 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.