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
Rattus norvegicus (Rat)
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

Fe2+1 Publication

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.

Pathwayi: 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. no protein annotated in this organism
  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)DescriptionActionsGraphical viewLength
Metal bindingi285Iron; via tele nitrogenCombined sources1 Publication1
Metal bindingi290Iron; via tele nitrogenCombined sources1 Publication1
Metal bindingi330IronCombined sources1 Publication1

GO - Molecular functioni

  • amino acid binding Source: RGD
  • cofactor binding Source: RGD
  • iron ion binding Source: RGD
  • phenylalanine 4-monooxygenase activity Source: RGD
  • protein homodimerization activity Source: RGD

GO - Biological processi

  • L-phenylalanine catabolic process Source: UniProtKB-UniPathway
  • L-phenylalanine metabolic process Source: RGD
  • protein hydroxylation Source: RGD
  • pteridine-containing compound metabolic process Source: RGD
  • tetrahydrobiopterin metabolic process Source: RGD
  • tyrosine biosynthetic process Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Phenylalanine catabolism

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.16.1. 5301.
SABIO-RKP04176.
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3248. Pah.

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3077.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002055502 – 453Phenylalanine-4-hydroxylaseAdd BLAST452

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei16Phosphoserine; by PKACombined sources1 Publication1

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

PaxDbiP04176.
PRIDEiP04176.

PTM databases

iPTMnetiP04176.
PhosphoSitePlusiP04176.

Interactioni

Subunit structurei

Homodimer and homotetramer.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000005844.

Chemistry databases

BindingDBiP04176.

Structurei

Secondary structure

1453
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 42Combined sources8
Helixi47 – 56Combined sources10
Turni57 – 59Combined sources3
Beta strandi64 – 69Combined sources6
Beta strandi76 – 81Combined sources6
Helixi85 – 87Combined sources3
Helixi88 – 100Combined sources13
Beta strandi106 – 110Combined sources5
Beta strandi117 – 119Combined sources3
Helixi125 – 129Combined sources5
Turni130 – 133Combined sources4
Turni147 – 150Combined sources4
Helixi152 – 166Combined sources15
Helixi181 – 201Combined sources21
Helixi204 – 216Combined sources13
Helixi227 – 238Combined sources12
Beta strandi241 – 244Combined sources4
Helixi251 – 258Combined sources8
Turni259 – 261Combined sources3
Beta strandi262 – 265Combined sources4
Helixi283 – 289Combined sources7
Helixi291 – 294Combined sources4
Helixi297 – 310Combined sources14
Helixi315 – 326Combined sources12
Turni327 – 331Combined sources5
Beta strandi333 – 336Combined sources4
Beta strandi339 – 342Combined sources4
Helixi345 – 348Combined sources4
Helixi351 – 357Combined sources7
Beta strandi359 – 366Combined sources8
Helixi369 – 372Combined sources4
Beta strandi379 – 382Combined sources4
Beta strandi384 – 390Combined sources7
Helixi392 – 403Combined sources12
Beta strandi409 – 415Combined sources7
Turni416 – 419Combined sources4
Beta strandi420 – 424Combined sources5
Helixi426 – 448Combined sources23

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PHZX-ray2.20A1-429[»]
2PHMX-ray2.60A1-429[»]
5DENX-ray2.90A/B/C/D1-453[»]
5EGQX-ray2.50A/B/C/D1-453[»]
5FGJX-ray3.60A/B/C/D1-453[»]
ProteinModelPortaliP04176.
SMRiP04176.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04176.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 114ACTPROSITE-ProRule annotationAdd BLAST79

Sequence similaritiesi

Contains 1 ACT domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3820. Eukaryota.
COG3186. LUCA.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP04176.
PhylomeDBiP04176.

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.

P04176-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAVVLENGV LSRKLSDFGQ ETSYIEDNSN QNGAISLIFS LKEEVGALAK
60 70 80 90 100
VLRLFEENDI NLTHIESRPS RLNKDEYEFF TYLDKRTKPV LGSIIKSLRN
110 120 130 140 150
DIGATVHELS RDKEKNTVPW FPRTIQELDR FANQILSYGA ELDADHPGFK
160 170 180 190 200
DPVYRARRKQ FADIAYNYRH GQPIPRVEYT EEEKQTWGTV 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 KTACQEYSVT EFQPLYYVAE SFSDAKEKVR
410 420 430 440 450
TFAATIPRPF SVRYDPYTQR VEVLDNTQQL KILADSINSE VGILCNALQK

IKS
Length:453
Mass (Da):51,822
Last modified:January 23, 2007 - v3
Checksum:i365D9E8A7E498D52
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12337 mRNA. Translation: AAA41843.1.
K02599 mRNA. Translation: AAA41794.1.
PIRiA25321. WHRTF.
UniGeneiRn.1652.

Genome annotation databases

UCSCiRGD:3248. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12337 mRNA. Translation: AAA41843.1.
K02599 mRNA. Translation: AAA41794.1.
PIRiA25321. WHRTF.
UniGeneiRn.1652.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PHZX-ray2.20A1-429[»]
2PHMX-ray2.60A1-429[»]
5DENX-ray2.90A/B/C/D1-453[»]
5EGQX-ray2.50A/B/C/D1-453[»]
5FGJX-ray3.60A/B/C/D1-453[»]
ProteinModelPortaliP04176.
SMRiP04176.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000005844.

Chemistry databases

BindingDBiP04176.
ChEMBLiCHEMBL3077.

PTM databases

iPTMnetiP04176.
PhosphoSitePlusiP04176.

Proteomic databases

PaxDbiP04176.
PRIDEiP04176.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:3248. rat.

Organism-specific databases

RGDi3248. Pah.

Phylogenomic databases

eggNOGiKOG3820. Eukaryota.
COG3186. LUCA.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP04176.
PhylomeDBiP04176.

Enzyme and pathway databases

UniPathwayiUPA00139; UER00337.
BRENDAi1.14.16.1. 5301.
SABIO-RKP04176.

Miscellaneous databases

EvolutionaryTraceiP04176.
PROiP04176.

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...

Entry informationi

Entry nameiPH4H_RAT
AccessioniPrimary (citable) accession number: P04176
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 155 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.