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    Pah phenylalanine hydroxylase [ Rattus norvegicus (Norway rat) ]

    Gene ID: 24616, updated on 9-Dec-2024

    Summary

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    Official Symbol
    Pahprovided by RGD
    Official Full Name
    phenylalanine hydroxylaseprovided by RGD
    Primary source
    RGD:3248
    See related
    EnsemblRapid: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, Dec 2024]
    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

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    See Pah in Genome Data Viewer
    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_086025.1Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC120093792 Neighboring gene uncharacterized LOC134479793 Neighboring gene achaete-scute family bHLH transcription factor 1 Neighboring gene mesoderm posterior bHLH transcription factor 2, pseudogene 1 Neighboring gene uncharacterized LOC120093845

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Insights into the catalytic mechanisms of phenylalanine and tryptophan hydroxylase from kinetic isotope effects on aromatic hydroxylation. Pavon JA, et al. Biochemistry, 2006 Sep 12. PMID 16953590, Free PMC Article
    2. Updated listing of haplotypes at the human phenylalanine hydroxylase (PAH) locus. Eisensmith RC, et al. Am J Hum Genet, 1992 Dec. PMID 1361103, Free PMC Article
    3. Structural basis of autoregulation of phenylalanine hydroxylase. Kobe B, et al. Nat Struct Biol, 1999 May. PMID 10331871
    4. Contrasting effects of N5-substituted tetrahydrobiopterin derivatives on phenylalanine hydroxylase, dihydropteridine reductase and nitric oxide synthase. Werner ER, et al. Biochem J, 2000 Jun 15. PMID 10839989, Free PMC Article
    5. Sequence analysis of the rat phenylalanine hydroxylase gene promoter. Rees D, et al. DNA Seq, 2001. PMID 11762195

    See all (30) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. the regulatory domain of phenylalanine hydroxylase can bind phenylalanine
      Title: Direct evidence for a phenylalanine site in the regulatory domain of phenylalanine hydroxylase.
    10. 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)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    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 protein hydroxylation 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
    		  

    General protein information

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    Preferred Names
    phenylalanine-4-hydroxylase
    Names
    phe-4-monooxygenase
    NP_036751.2
    XP_038934345.1
    XP_063119065.1

    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)

    1. 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, ENSRNOT00000005844.9
      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

    1. NC_086025.1 Reference GRCr8

      Range
      23793096..23885631
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      UniProtKB/Swiss-Prot
      P04176
      UniProtKB/TrEMBL
      F7FDL3, Q6AYW2
      Related
      ENSRNOP00000100444.1, ENSRNOT00000141209.1

    2. 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
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P04176.3 GenPept UniProtKB/Swiss-Prot:P04176

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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