Pah phenylalanine hydroxylase [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Pahprovided by RGD
Official Full Name: phenylalanine hydroxylaseprovided by RGD
Primary source: RGD:3248
See related: Ensembl:ENSRNOG00000004302 AllianceGenome:RGD:3248
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Enables several functions, including identical protein binding activity; iron ion binding activity; and phenylalanine 4-monooxygenase activity. Involved in L-phenylalanine metabolic process; protein hydroxylation; and tyrosine biosynthetic process, by oxidation of phenylalanine. Human ortholog(s) of this gene implicated in intellectual disability and phenylketonuria. Orthologous to human PAH (phenylalanine hydroxylase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Liver (RPKM 3669.4) and Kidney (RPKM 3394.4) See more
Orthologs: human mouse all
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Genomic context

Location:: 7q13

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	7	NC_086025.1 (23793096..23885631)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	7	NC_051342.1 (21933179..21998134)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	7	NC_005106.4 (28066639..28129772)

Chromosome 7 - NC_086025.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Manipulation of a cation-pi sandwich reveals conformational flexibility in phenylalanine hydroxylase.
Title: Manipulation of a cation-π sandwich reveals conformational flexibility in phenylalanine hydroxylase.
results support a model for allostery in PheH in which phenylalanine stabilizes the dimerization of the regulatory domains and exposes the active site for substrate binding and other structural changes needed for activity
Title: Domain Movements upon Activation of Phenylalanine Hydroxylase Characterized by Crystallography and Chromatography-Coupled Small-Angle X-ray Scattering.
The results identify the location of the allosteric site as the interface of the regulatory domain dimer formed in activated PheH.
Title: Identification of the Allosteric Site for Phenylalanine in Rat Phenylalanine Hydroxylase.
use of SAXS and X-ray crystallography together to inspect PAH structure provides, to our knowledge, the first complete view of the enzyme in a tetrameric form that was not possible with prior partial crystal structures
Title: First structure of full-length mammalian phenylalanine hydroxylase reveals the architecture of an autoinhibited tetramer.
allosteric activation of phenylalanine hydroxylase is linked to dimerization of regulatory domains
Title: The Amino Acid Specificity for Activation of Phenylalanine Hydroxylase Matches the Specificity for Stabilization of Regulatory Domain Dimers.
Data suggest that phenylalanine [concentration-dependent] activation of phenylalanine hydroxylase does not involve the active site; mutating the active-site residue Arg270 to lysine abolishes phenylalanine-dependent enzyme activation.
Title: Activation of phenylalanine hydroxylase by phenylalanine does not require binding in the active site.
the conformational change upon phosphorylation of phenylalanine hydroxylase is different from and less extensive than that upon phenylalanine activation.
Title: Regulation of phenylalanine hydroxylase: conformational changes upon phosphorylation detected by H/D exchange and mass spectrometry.
A new model for allosteric regulation of phenylalanine hydroxylase: implications for disease and therapeutics.
Title: A new model for allosteric regulation of phenylalanine hydroxylase: implications for disease and therapeutics.
the regulatory domain of phenylalanine hydroxylase can bind phenylalanine
Title: Direct evidence for a phenylalanine site in the regulatory domain of phenylalanine hydroxylase.
Metal ligand mutants of Pah are characterized.
Title: Characterization of metal ligand mutants of phenylalanine hydroxylase: Insights into the plasticity of a 2-histidine-1-carboxylate triad.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PAH (e-PCR), detects polymorphism
- UniSTS:266309

D7Rat225 (e-PCR), detects polymorphism
- UniSTS:228173

RH94480 (e-PCR)
- UniSTS:119728

RH127306 (e-PCR)
- UniSTS:210616

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables amino acid binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables iron ion binding	IDA Inferred from Direct Assay more info	PubMed
enables iron ion binding	IEA Inferred from Electronic Annotation more info
enables phenylalanine 4-monooxygenase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phenylalanine 4-monooxygenase activity	IDA Inferred from Direct Assay more info	PubMed
enables phenylalanine 4-monooxygenase activity	IEA Inferred from Electronic Annotation more info
enables phenylalanine 4-monooxygenase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in L-phenylalanine catabolic process	IEA Inferred from Electronic Annotation more info
involved_in L-phenylalanine metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in tyrosine biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in tyrosine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in tyrosine biosynthetic process, by oxidation of phenylalanine	IDA Inferred from Direct Assay more info	PubMed
involved_in tyrosine biosynthetic process, by oxidation of phenylalanine	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within tyrosine biosynthetic process, by oxidation of phenylalanine	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: phenylalanine-4-hydroxylase

Names: phe-4-monooxygenase

NP_036751.2

EC 1.14.16.1

XP_038934345.1

EC 1.14.16.1

XP_063119065.1

EC 1.14.16.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_012619.2 → NP_036751.2 phenylalanine-4-hydroxylase

See identical proteins and their annotated locations for NP_036751.2

Status: PROVISIONAL

Source sequence(s)

BC078881

UniProtKB/Swiss-Prot

P04176

UniProtKB/TrEMBL

F7FDL3, Q6AYW2

Related

ENSRNOP00000005844.4, ENSRNOT00000005844.8

Conserved Domains (3) summary

TIGR01268
Location:20 → 452

Phe4hydrox_tetr; phenylalanine-4-hydroxylase, tetrameric form

cd04931
Location:21 → 110

ACT_PAH; ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, phenylalanine hydroxylases (PAH)

pfam00351
Location:119 → 449

Biopterin_H; Biopterin-dependent aromatic amino acid hydroxylase

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086025.1 Reference GRCr8

Range

23793096..23885631

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063262995.1 → XP_063119065.1 phenylalanine-4-hydroxylase isoform X1

UniProtKB/TrEMBL

F7FDL3, Q6AYW2
XM_039078417.2 → XP_038934345.1 phenylalanine-4-hydroxylase isoform X2

Conserved Domains (1) summary

pfam00351
Location:32 → 362

Biopterin_H; Biopterin-dependent aromatic amino acid hydroxylase