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Protein

Phenylalanine-4-hydroxylase

Gene

PAH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine.2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Fe2+By similarity

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity 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.2 Publications

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=150 µM for L-phenylalanine1 Publication
  2. KM=154 µM for L-phenylalanine (at 25 degrees Celsius)1 Publication
  3. KM=30 µM for tetrahydrobiopterin (BH4)1 Publication
  4. KM=36 µM for tetrahydrobiopterin (BH4) (at 25 degrees Celsius)1 Publication
  1. Vmax=3500 nmol/min/mg enzyme towards L-phenylalanine (at 25 degrees Celsius)1 Publication
  2. Vmax=3600 nmol/min/mg enzyme towards tetrahydrobiopterin (BH4) (at 25 degrees Celsius)1 Publication
  3. Vmax=3640 nmol/min/mg enzyme towards L-phenylalanine (preincubated with L-Phe)1 Publication
  4. Vmax=1230 nmol/min/mg enzyme towards L-phenylalanine (preincubated with BH4)1 Publication

Temperature dependencei

Optimum temperature is 50 degrees Celsius.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>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. 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)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi285Iron; via tele nitrogenBy similarity1
Metal bindingi290Iron; via tele nitrogenBy similarity1
Metal bindingi330IronBy similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

  • iron ion binding Source: InterPro
  • phenylalanine 4-monooxygenase activity Source: CACAO

GO - Biological processi

  • catecholamine biosynthetic process Source: BHF-UCL
  • cellular amino acid biosynthetic process Source: ProtInc
  • L-phenylalanine catabolic process Source: Reactome
  • neurotransmitter biosynthetic process Source: BHF-UCL
  • tyrosine biosynthetic process Source: GO_Central

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionAllosteric enzyme, Monooxygenase, Oxidoreductase
Biological processPhenylalanine catabolism
LigandIron, Metal-binding

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

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BioCyci
MetaCyc:HS10374-MONOMER

BRENDA Comprehensive Enzyme Information System

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BRENDAi
1.14.16.1 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-2160456 Phenylketonuria
R-HSA-71182 Phenylalanine and tyrosine catabolism

SABIO-RK: Biochemical Reaction Kinetics Database

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SABIO-RKi
P00439

SIGNOR Signaling Network Open Resource

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SIGNORi
P00439

UniPathway: a resource for the exploration and annotation of metabolic pathways

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UniPathwayi
UPA00139;UER00337

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Phenylalanine-4-hydroxylase (EC:1.14.16.12 Publications)
Short name:
PAH
Alternative name(s):
Phe-4-monooxygenase
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:PAH
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 12

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000171759.9

Human Gene Nomenclature Database

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HGNCi
HGNC:8582 PAH

Online Mendelian Inheritance in Man (OMIM)

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MIMi
612349 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P00439

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Phenylketonuria (PKU)38 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.
See also OMIM:261600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_00086916S → P in PKU. Corresponds to variant dbSNP:rs62642946EnsemblClinVar.1
Natural variantiVAR_00087039F → L in HPA and PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62642926EnsemblClinVar.1
Natural variantiVAR_00087139Missing in PKU; haplotypes 9,21. 2 Publications1
Natural variantiVAR_00087240S → L in PKU. 1 PublicationCorresponds to variant dbSNP:rs62642938EnsemblClinVar.1
Natural variantiVAR_00087341L → F in PKU. Corresponds to variant dbSNP:rs62642928EnsemblClinVar.1
Natural variantiVAR_00924041L → P in PKU; mild. Corresponds to variant dbSNP:rs62642916EnsemblClinVar.1
Natural variantiVAR_00087442K → I in PKU; haplotype 21. Corresponds to variant dbSNP:rs62635346EnsemblClinVar.1
Natural variantiVAR_06799445V → A in PKU. 1 Publication1
Natural variantiVAR_00087546G → S in PKU; haplotype 5; significantly reduces phenylalanine binding. 1 PublicationCorresponds to variant dbSNP:rs74603784EnsemblClinVar.1
Natural variantiVAR_00087748L → S in PKU; mild; haplotypes 3,4. 5 PublicationsCorresponds to variant dbSNP:rs5030841EnsemblClinVar.1
Natural variantiVAR_00087853R → H in PKU. 1 PublicationCorresponds to variant dbSNP:rs118092776EnsemblClinVar.1
Natural variantiVAR_00087955F → L in HPA and PKU; does not affect oligomerization; results in loss of substrate activation. 3 PublicationsCorresponds to variant dbSNP:rs199475598EnsemblClinVar.1
Natural variantiVAR_00088056E → D in PKU; haplotype 10. Corresponds to variant dbSNP:rs199475567EnsemblClinVar.1
Natural variantiVAR_06799561N → D in PKU. 1 PublicationCorresponds to variant dbSNP:rs199475651EnsemblClinVar.1
Natural variantiVAR_06799662L → P in PKU. 1 Publication1
Natural variantiVAR_00088163 – 64TH → PN in PKU; haplotype 1; abolishes phenylalanine binding. 2
Natural variantiVAR_00088265I → N in PKU. 1 PublicationCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_06799765I → S in PKU; results in disturbed oligomerization; results in loss of substrate activation. 2 PublicationsCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_00088365I → T in PKU; haplotypes 1,5,9,21,B; abolishes phenylalanine binding. 3 PublicationsCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_06799865I → V in HPA and PKU. 2 PublicationsCorresponds to variant dbSNP:rs199475643EnsemblClinVar.1
Natural variantiVAR_00088467S → P in PKU; haplotype 4. Corresponds to variant dbSNP:rs5030842EnsemblClinVar.1
Natural variantiVAR_00088568R → S in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs76394784EnsemblClinVar.1
Natural variantiVAR_00088676E → A in PKU. Corresponds to variant dbSNP:rs62507347EnsemblClinVar.1
Natural variantiVAR_00088784D → Y in PKU; haplotype 4. Corresponds to variant dbSNP:rs62514902EnsemblClinVar.1
Natural variantiVAR_00088992T → I in PKU. Corresponds to variant dbSNP:rs62514903EnsemblClinVar.1
Natural variantiVAR_00089094Missing in PKU; mild; haplotype 2. 1 Publication1
Natural variantiVAR_000892104A → D in PKU; mild; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62642929EnsemblClinVar.1
Natural variantiVAR_000893124T → I in PKU; haplotype 28. Corresponds to variant dbSNP:rs199475571EnsemblClinVar.1
Natural variantiVAR_000894129D → Y in PKU. Corresponds to variant dbSNP:rs199475606EnsemblClinVar.1
Natural variantiVAR_000895143D → G in PKU; haplotype 11. 1 PublicationCorresponds to variant dbSNP:rs199475572EnsemblClinVar.1
Natural variantiVAR_011566145D → V in PKU. Corresponds to variant dbSNP:rs140175796EnsemblClinVar.1
Natural variantiVAR_000896146H → Y in PKU. Corresponds to variant dbSNP:rs199475599EnsemblClinVar.1
Natural variantiVAR_000897148G → S in PKU; haplotypes 1,2,7. Corresponds to variant dbSNP:rs80297647EnsemblClinVar.1
Natural variantiVAR_000898151D → H in PKU; haplotypes 1,8. Corresponds to variant dbSNP:rs199475597EnsemblClinVar.1
Natural variantiVAR_000899154Y → N in PKU. Corresponds to variant dbSNP:rs199475587EnsemblClinVar.1
Natural variantiVAR_009242155R → P in PKU. Corresponds to variant dbSNP:rs199475663EnsemblClinVar.1
Natural variantiVAR_000900157R → N in PKU; severe; 5% activity; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_068000157R → S in PKU. 1 PublicationCorresponds to variant dbSNP:rs199475612EnsemblClinVar.1
Natural variantiVAR_000901158R → Q in PKU; haplotypes 1,2,4,7,16, 28. 3 PublicationsCorresponds to variant dbSNP:rs5030843EnsemblClinVar.1
Natural variantiVAR_000902158R → W in PKU. Corresponds to variant dbSNP:rs75166491EnsemblClinVar.1
Natural variantiVAR_000903160Q → P in PKU. Corresponds to variant dbSNP:rs199475601EnsemblClinVar.1
Natural variantiVAR_000904161F → S in PKU; haplotype 4. Corresponds to variant dbSNP:rs79635844EnsemblClinVar.1
Natural variantiVAR_000905164I → T in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs199475595EnsemblClinVar.1
Natural variantiVAR_000906167N → I in PKU. 1 PublicationCorresponds to variant dbSNP:rs77554925EnsemblClinVar.1
Natural variantiVAR_011568169R → H in PKU. Corresponds to variant dbSNP:rs199475679EnsemblClinVar.1
Natural variantiVAR_068001170H → Q in PKU; does not affect oligomerization. 2 PublicationsCorresponds to variant dbSNP:rs199475652EnsemblClinVar.1
Natural variantiVAR_000907170H → R in PKU. Corresponds to variant dbSNP:rs199475573EnsemblClinVar.1
Natural variantiVAR_000908171G → A in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs199475596EnsemblClinVar.1
Natural variantiVAR_000909171G → R in PKU. Corresponds to variant dbSNP:rs199475613EnsemblClinVar.1
Natural variantiVAR_000910173P → T in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475574EnsemblClinVar.1
Natural variantiVAR_000911174I → T in PKU; haplotype 1. Corresponds to variant dbSNP:rs138809906EnsemblClinVar.1
Natural variantiVAR_011570174I → V in PKU. Corresponds to variant dbSNP:rs199475632EnsemblClinVar.1
Natural variantiVAR_000912175P → A in PKU. Corresponds to variant dbSNP:rs199475604EnsemblClinVar.1
Natural variantiVAR_000914176R → P in PKU. Corresponds to variant dbSNP:rs74486803EnsemblClinVar.1
Natural variantiVAR_000915177V → L in PKU; haplotype 6. 1 PublicationCorresponds to variant dbSNP:rs199475602EnsemblClinVar.1
Natural variantiVAR_009243183E → Q in PKU. Corresponds to variant dbSNP:rs199475664EnsemblClinVar.1
Natural variantiVAR_000917190V → A in PKU; haplotype 3. 2 PublicationsCorresponds to variant dbSNP:rs62514919EnsemblClinVar.1
Natural variantiVAR_000918194L → P in PKU. Corresponds to variant dbSNP:rs5030844EnsemblClinVar.1
Natural variantiVAR_000919194Missing in PKU. 1
Natural variantiVAR_000920197Missing in PKU. 1
Natural variantiVAR_000921198Missing in PKU; haplotype 2. 1
Natural variantiVAR_000922201H → R in PKU. Corresponds to variant dbSNP:rs62517180EnsemblClinVar.1
Natural variantiVAR_000924204Y → C in PKU; mild; haplotypes 3,4. 1 PublicationCorresponds to variant dbSNP:rs62514927EnsemblClinVar.1
Natural variantiVAR_011571205E → A in PKU. Corresponds to variant dbSNP:rs62508593EnsemblClinVar.1
Natural variantiVAR_000925206Y → D in PKU. Corresponds to variant dbSNP:rs62517170EnsemblClinVar.1
Natural variantiVAR_000926207N → D in PKU. 1 PublicationCorresponds to variant dbSNP:rs62508572EnsemblClinVar.1
Natural variantiVAR_000927207N → S in PKU; severe; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62508721EnsemblClinVar.1
Natural variantiVAR_000928211P → T in PKU; haplotype 4. Corresponds to variant dbSNP:rs62514931EnsemblClinVar.1
Natural variantiVAR_000929212L → P in PKU. Corresponds to variant dbSNP:rs62517198EnsemblClinVar.1
Natural variantiVAR_000930213L → P in PKU; severe. 1 PublicationCorresponds to variant dbSNP:rs62516109EnsemblClinVar.1
Natural variantiVAR_000931217C → G in PKU. Corresponds to variant dbSNP:rs62508718EnsemblClinVar.1
Natural variantiVAR_000932218G → V in PKU; haplotypes 1,2. Corresponds to variant dbSNP:rs62514933EnsemblClinVar.1
Natural variantiVAR_000933221E → G in PKU; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62514934EnsemblClinVar.1
Natural variantiVAR_000934222D → V in PKU; haplotypes 3,4. Corresponds to variant dbSNP:rs62507319EnsemblClinVar.1
Natural variantiVAR_000935224I → M in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475576EnsemblClinVar.1
Natural variantiVAR_000936225P → R in PKU. Corresponds to variant dbSNP:rs62517204EnsemblClinVar.1
Natural variantiVAR_000937225P → T in PKU; haplotype 1. Corresponds to variant dbSNP:rs199475589EnsemblClinVar.1
Natural variantiVAR_068003226Q → H in PKU. 1 PublicationCorresponds to variant dbSNP:rs62508615EnsemblClinVar.1
Natural variantiVAR_009244231S → F in PKU. Corresponds to variant dbSNP:rs62508577EnsemblClinVar.1
Natural variantiVAR_000939231S → P in PKU. Corresponds to variant dbSNP:rs5030845EnsemblClinVar.1
Natural variantiVAR_000940233F → L in PKU; haplotypes 2,3. Corresponds to variant dbSNP:rs62517208EnsemblClinVar.1
Natural variantiVAR_000941238T → P in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475577EnsemblClinVar.1
Natural variantiVAR_000942239G → S in PKU. 1 PublicationCorresponds to variant dbSNP:rs62517178EnsemblClinVar.1
Natural variantiVAR_011572240F → S in PKU. Corresponds to variant dbSNP:rs62508594EnsemblClinVar.1
Natural variantiVAR_000943241R → C in non-PKU HPA and PKU; haplotype 34. 3 PublicationsCorresponds to variant dbSNP:rs76687508EnsemblClinVar.1
Natural variantiVAR_000944241R → H in PKU; haplotypes 1,5. Corresponds to variant dbSNP:rs62508730EnsemblClinVar.1
Natural variantiVAR_000945241R → L in PKU. Corresponds to variant dbSNP:rs62508730EnsemblClinVar.1
Natural variantiVAR_000946242L → F in PKU. Corresponds to variant dbSNP:rs199475578EnsemblClinVar.1
Natural variantiVAR_000947243R → Q in non-PKU HPA and PKU; haplotypes 4,7,9. 2 PublicationsCorresponds to variant dbSNP:rs62508588EnsemblClinVar.1
Natural variantiVAR_000948244P → L in PKU; haplotype 12. 1 PublicationCorresponds to variant dbSNP:rs118203923EnsemblClinVar.1
Natural variantiVAR_000949245V → A in PKU, HPA and non-PKU HPA; haplotypes 3,7. 4 PublicationsCorresponds to variant dbSNP:rs796052017EnsemblClinVar.1
Natural variantiVAR_000950245V → E in PKU; haplotype 11. Corresponds to variant dbSNP:rs76212747EnsemblClinVar.1
Natural variantiVAR_000951245V → L in PKU. Corresponds to variant dbSNP:rs62508694EnsemblClinVar.1
Natural variantiVAR_000952246A → D in PKU. Corresponds to variant dbSNP:rs199475610EnsemblClinVar.1
Natural variantiVAR_000953247G → V in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475579EnsemblClinVar.1
Natural variantiVAR_000954248L → P in PKU. Corresponds to variant dbSNP:rs62507340EnsemblClinVar.1
Natural variantiVAR_000955249L → F in PKU; haplotype 1. Corresponds to variant dbSNP:rs74503222EnsemblClinVar.1
Natural variantiVAR_000956252R → G in PKU; haplotype 7. Corresponds to variant dbSNP:rs5030847EnsemblClinVar.1
Natural variantiVAR_000957252R → Q in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62644503EnsemblClinVar.1
Natural variantiVAR_000958252R → W in PKU; haplotypes 1,6,7,8,42, 69; complete loss of activity. 4 PublicationsCorresponds to variant dbSNP:rs5030847EnsemblClinVar.1
Natural variantiVAR_000960255L → S in PKU; haplotype 36. 1 PublicationCorresponds to variant dbSNP:rs62642930EnsemblClinVar.1
Natural variantiVAR_000959255L → V in PKU; haplotypes 18,21. Corresponds to variant dbSNP:rs62642931EnsemblClinVar.1
Natural variantiVAR_000961257G → C in PKU. Corresponds to variant dbSNP:rs5030848EnsemblClinVar.1
Natural variantiVAR_000962259A → T in PKU; haplotype 3. Corresponds to variant dbSNP:rs62642932EnsemblClinVar.1
Natural variantiVAR_000963259A → V in PKU; haplotypes 7,42. Corresponds to variant dbSNP:rs118203921EnsemblClinVar.1
Natural variantiVAR_000964261R → P in PKU. Corresponds to variant dbSNP:rs5030849EnsemblClinVar.1
Natural variantiVAR_000965261R → Q in HPA and PKU; mild; haplotypes 1,2,4,22, 24,28. 5 PublicationsCorresponds to variant dbSNP:rs5030849EnsemblClinVar.1
Natural variantiVAR_000966263F → L in PKU. Corresponds to variant dbSNP:rs62642944EnsemblClinVar.1
Natural variantiVAR_000967264H → L in PKU. Corresponds to variant dbSNP:rs199475580EnsemblClinVar.1
Natural variantiVAR_000968265C → G in PKU. Corresponds to variant dbSNP:rs62517181EnsemblClinVar.1
Natural variantiVAR_000970270R → K in PKU. Corresponds to variant dbSNP:rs62514950EnsemblClinVar.1
Natural variantiVAR_000971270R → S in PKU; haplotype 1. Corresponds to variant dbSNP:rs62514951EnsemblClinVar.1
Natural variantiVAR_000972271H → Y in PKU. Corresponds to variant dbSNP:rs62517164EnsemblClinVar.1
Natural variantiVAR_000973273S → F in PKU; haplotype 7. Corresponds to variant dbSNP:rs62514953EnsemblClinVar.1
Natural variantiVAR_068004275P → L in PKU; reduced activity; increased affinity for the substrate; mildly reduced substrate activation; decreased cofactor affinity. 2 PublicationsCorresponds to variant dbSNP:rs62508715EnsemblClinVar.1
Natural variantiVAR_000974276M → I in PKU. Corresponds to variant dbSNP:rs62514954EnsemblClinVar.1
Natural variantiVAR_000975276M → V in PKU; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62516149EnsemblClinVar.1
Natural variantiVAR_000976277Y → C in PKU. Corresponds to variant dbSNP:rs62516155EnsemblClinVar.1
Natural variantiVAR_000977277Y → D in PKU; haplotype 2. Corresponds to variant dbSNP:rs78655458EnsemblClinVar.1
Natural variantiVAR_000978278T → A in PKU. Corresponds to variant dbSNP:rs62516156EnsemblClinVar.1
Natural variantiVAR_000979278T → N in PKU. Corresponds to variant dbSNP:rs62507262EnsemblClinVar.1
Natural variantiVAR_000980280E → K in PKU; haplotypes 1,2,4,16,38; partial residual activity. 3 PublicationsCorresponds to variant dbSNP:rs62508698EnsemblClinVar.1
Natural variantiVAR_000981281P → L in PKU; haplotypes 1,4. 5 PublicationsCorresponds to variant dbSNP:rs5030851EnsemblClinVar.1
Natural variantiVAR_000982282D → N in PKU; haplotype 1. Corresponds to variant dbSNP:rs199475582EnsemblClinVar.1
Natural variantiVAR_000983283I → F in PKU; haplotype 21. Corresponds to variant dbSNP:rs62517168EnsemblClinVar.1
Natural variantiVAR_000984283I → N in PKU; severe. 1 PublicationCorresponds to variant dbSNP:rs62508693EnsemblClinVar.1
Natural variantiVAR_067758290H → Y in PKU. 1 PublicationCorresponds to variant dbSNP:rs1486763160Ensembl.1
Natural variantiVAR_000985297R → C in PKU; haplotype 4. Corresponds to variant dbSNP:rs62642945EnsemblClinVar.1
Natural variantiVAR_000986297R → H in PKU. Corresponds to variant dbSNP:rs62642939EnsemblClinVar.1
Natural variantiVAR_000987299F → C in PKU; haplotype 8. 1 PublicationCorresponds to variant dbSNP:rs62642933EnsemblClinVar.1
Natural variantiVAR_000988300A → S in PKU and HPA; haplotype 1; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 4 PublicationsCorresponds to variant dbSNP:rs5030853EnsemblClinVar.1
Natural variantiVAR_000989300A → V in PKU. Corresponds to variant dbSNP:rs199475609EnsemblClinVar.1
Natural variantiVAR_000990303S → P in PKU; haplotype 5. Corresponds to variant dbSNP:rs199475608EnsemblClinVar.1
Natural variantiVAR_000991304Q → R in PKU. Corresponds to variant dbSNP:rs199475592EnsemblClinVar.1
Natural variantiVAR_000993309A → D in PKU; haplotype 7. Corresponds to variant dbSNP:rs62642935EnsemblClinVar.1
Natural variantiVAR_000994309A → V in PKU. Corresponds to variant dbSNP:rs62642935EnsemblClinVar.1
Natural variantiVAR_000995310S → F in PKU; haplotype 7. Corresponds to variant dbSNP:rs62642913EnsemblClinVar.1
Natural variantiVAR_000996311L → P in PKU; haplotypes 1,7,10. 2 PublicationsCorresponds to variant dbSNP:rs62642936EnsemblClinVar.1
Natural variantiVAR_000997314P → H in PKU. Corresponds to variant dbSNP:rs62642940EnsemblClinVar.1
Natural variantiVAR_011574318I → T in PKU; partial loss of activity. 1 PublicationCorresponds to variant dbSNP:rs62642918EnsemblClinVar.1
Natural variantiVAR_000998322A → G in PKU; haplotype 12. Corresponds to variant dbSNP:rs62514958EnsemblClinVar.1
Natural variantiVAR_000999322A → T in PKU; haplotype 1. Corresponds to variant dbSNP:rs62514957EnsemblClinVar.1
Natural variantiVAR_067759322A → V in PKU. 1 PublicationCorresponds to variant dbSNP:rs62514958EnsemblClinVar.1
Natural variantiVAR_009245325Y → C in PKU. Corresponds to variant dbSNP:rs62508578EnsemblClinVar.1
Natural variantiVAR_009246330E → D in PKU. Corresponds to variant dbSNP:rs62508580EnsemblClinVar.1
Natural variantiVAR_001000331F → L in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62517179EnsemblClinVar.1
Natural variantiVAR_001001333L → F in PKU. Corresponds to variant dbSNP:rs62516060EnsemblClinVar.1
Natural variantiVAR_001002334C → S in PKU. Corresponds to variant dbSNP:rs62517174EnsemblClinVar.1
Natural variantiVAR_001003337G → V in PKU. Corresponds to variant dbSNP:rs62517206EnsemblClinVar.1
Natural variantiVAR_001004338D → Y in PKU; haplotype 4. Corresponds to variant dbSNP:rs62516150EnsemblClinVar.1
Natural variantiVAR_001005341K → R in PKU. Corresponds to variant dbSNP:rs62516153EnsemblClinVar.1
Natural variantiVAR_001006341K → T in PKU. Corresponds to variant dbSNP:rs62516153EnsemblClinVar.1
Natural variantiVAR_001007342A → T in PKU; haplotype 5. Corresponds to variant dbSNP:rs62507282EnsemblClinVar.1
Natural variantiVAR_001008343Y → C in PKU. Corresponds to variant dbSNP:rs62507265EnsemblClinVar.1
Natural variantiVAR_009247344G → R in PKU. Corresponds to variant dbSNP:rs62508679EnsemblClinVar.1
Natural variantiVAR_009248344G → V in PKU. Corresponds to variant dbSNP:rs62508582EnsemblClinVar.1
Natural variantiVAR_001009345A → S in PKU. Corresponds to variant dbSNP:rs62516062EnsemblClinVar.1
Natural variantiVAR_001010345A → T in PKU; haplotype 7. Corresponds to variant dbSNP:rs62516062EnsemblClinVar.1
Natural variantiVAR_001011347L → F in PKU. Corresponds to variant dbSNP:rs62516154EnsemblClinVar.1
Natural variantiVAR_001012348L → V in PKU; mild haplotype 9. Corresponds to variant dbSNP:rs62516092EnsemblClinVar.1
Natural variantiVAR_001013349S → L in PKU; severe. 1 PublicationCorresponds to variant dbSNP:rs62507279EnsemblClinVar.1
Natural variantiVAR_001014349S → P in PKU; haplotypes 1,4. 1 PublicationCorresponds to variant dbSNP:rs62508646EnsemblClinVar.1
Natural variantiVAR_001015350S → T in PKU; haplotype 2. Corresponds to variant dbSNP:rs62517183EnsemblClinVar.1
Natural variantiVAR_011575357C → G in PKU. Corresponds to variant dbSNP:rs62508595EnsemblClinVar.1
Natural variantiVAR_001016362P → T in PKU. 1 PublicationCorresponds to variant dbSNP:rs62507329EnsemblClinVar.1
Natural variantiVAR_001018364 – 368Missing in PKU. 1 Publication5
Natural variantiVAR_001017364Missing in PKU; haplotype 5. 1 Publication1
Natural variantiVAR_001019366P → H in PKU. Corresponds to variant dbSNP:rs62516098EnsemblClinVar.1
Natural variantiVAR_001020372T → S in PKU. Corresponds to variant dbSNP:rs62517163EnsemblClinVar.1
Natural variantiVAR_001021377Y → C in PKU; haplotype 4. Corresponds to variant dbSNP:rs62642942EnsemblClinVar.1
Natural variantiVAR_001023386Y → C in PKU; common mutation. Corresponds to variant dbSNP:rs62516141EnsemblClinVar.1
Natural variantiVAR_001024387Y → H in PKU; haplotype 1. Corresponds to variant dbSNP:rs62517194EnsemblClinVar.1
Natural variantiVAR_001025388V → L in PKU. 1 PublicationCorresponds to variant dbSNP:rs62516101EnsemblClinVar.1
Natural variantiVAR_001026388V → M in PKU; haplotypes 1,4. Corresponds to variant dbSNP:rs62516101EnsemblClinVar.1
Natural variantiVAR_001027390E → G in PKU and non-PKU HPA; haplotype 4. 5 PublicationsCorresponds to variant dbSNP:rs5030856EnsemblClinVar.1
Natural variantiVAR_001028394D → A in PKU. Corresponds to variant dbSNP:rs62516102EnsemblClinVar.1
Natural variantiVAR_001029394D → H in PKU. 1 PublicationCorresponds to variant dbSNP:rs62516142EnsemblClinVar.1
Natural variantiVAR_001030395A → G in PKU. Corresponds to variant dbSNP:rs62508736EnsemblClinVar.1
Natural variantiVAR_001031395A → P in PKU; haplotype 1. Corresponds to variant dbSNP:rs62516103EnsemblClinVar.1
Natural variantiVAR_001032399 – 400Missing in PKU; haplotype 7. 2
Natural variantiVAR_001033403A → V in non-PKU HPA and PKU; haplotype 43. 4 PublicationsCorresponds to variant dbSNP:rs5030857EnsemblClinVar.1
Natural variantiVAR_068007407P → L in PKU. 1 PublicationCorresponds to variant dbSNP:rs62644473EnsemblClinVar.1
Natural variantiVAR_011576407P → S in PKU. Corresponds to variant dbSNP:rs62644465EnsemblClinVar.1
Natural variantiVAR_001034408R → Q in PKU; haplotypes 4,12. 1 PublicationCorresponds to variant dbSNP:rs5030859EnsemblClinVar.1
Natural variantiVAR_001035408R → W in HPA and PKU; haplotypes 1,2,4,5,13,34, 41,44; most common mutation; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 8 PublicationsCorresponds to variant dbSNP:rs5030858EnsemblClinVar.1
Natural variantiVAR_009249410F → S in PKU; mild. Corresponds to variant dbSNP:rs62644475EnsemblClinVar.1
Natural variantiVAR_001036413R → P in non-PKU HPA and PKU; haplotype 4. 2 PublicationsCorresponds to variant dbSNP:rs79931499EnsemblClinVar.1
Natural variantiVAR_001037413R → S in PKU; haplotype 1. Corresponds to variant dbSNP:rs62644467EnsemblClinVar.1
Natural variantiVAR_001038414Y → C in HPA and PKU; haplotype 4; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 3 PublicationsCorresponds to variant dbSNP:rs5030860EnsemblClinVar.1
Natural variantiVAR_001039415D → N in PKU, HPA and non-PKU HPA; haplotype 1. 3 PublicationsCorresponds to variant dbSNP:rs62644499EnsemblClinVar.1
Natural variantiVAR_068008417Y → H in PKU; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 2 PublicationsCorresponds to variant dbSNP:rs62644471EnsemblClinVar.1
Natural variantiVAR_001040418T → P in PKU; haplotype 4. Corresponds to variant dbSNP:rs62644501EnsemblClinVar.1
Natural variantiVAR_067760421I → S in PKU. 1 Publication1
Natural variantiVAR_001041430L → P in PKU. Corresponds to variant dbSNP:rs199475607EnsemblClinVar.1
Natural variantiVAR_001042447A → D in PKU. Corresponds to variant dbSNP:rs76542238EnsemblClinVar.1
Non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one.
See also OMIM:261600
Hyperphenylalaninemia (HPA)9 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMildest form of phenylalanine hydroxylase deficiency.
See also OMIM:261600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00923920Q → L in HPA. Corresponds to variant dbSNP:rs199475662EnsemblClinVar.1
Natural variantiVAR_00087039F → L in HPA and PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62642926EnsemblClinVar.1
Natural variantiVAR_00087955F → L in HPA and PKU; does not affect oligomerization; results in loss of substrate activation. 3 PublicationsCorresponds to variant dbSNP:rs199475598EnsemblClinVar.1
Natural variantiVAR_06799865I → V in HPA and PKU. 2 PublicationsCorresponds to variant dbSNP:rs199475643EnsemblClinVar.1
Natural variantiVAR_009241110S → C in HPA. 1
Natural variantiVAR_069776121F → L in HPA. 1 Publication1
Natural variantiVAR_011567167N → S in HPA. Corresponds to variant dbSNP:rs77554925EnsemblClinVar.1
Natural variantiVAR_011569170H → D in HPA. Corresponds to variant dbSNP:rs199475655EnsemblClinVar.1
Natural variantiVAR_068002177V → M in HPA. 1 PublicationCorresponds to variant dbSNP:rs199475602EnsemblClinVar.1
Natural variantiVAR_069777196S → Y in HPA. 1 PublicationCorresponds to variant dbSNP:rs865899394EnsemblClinVar.1
Natural variantiVAR_000965261R → Q in HPA and PKU; mild; haplotypes 1,2,4,22, 24,28. 5 PublicationsCorresponds to variant dbSNP:rs5030849EnsemblClinVar.1
Natural variantiVAR_000988300A → S in PKU and HPA; haplotype 1; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 4 PublicationsCorresponds to variant dbSNP:rs5030853EnsemblClinVar.1
Natural variantiVAR_068005310S → Y in HPA; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 2 PublicationsCorresponds to variant dbSNP:rs62642913EnsemblClinVar.1
Natural variantiVAR_068006314P → S in HPA; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 2 PublicationsCorresponds to variant dbSNP:rs199475650EnsemblClinVar.1
Natural variantiVAR_001035408R → W in HPA and PKU; haplotypes 1,2,4,5,13,34, 41,44; most common mutation; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 8 PublicationsCorresponds to variant dbSNP:rs5030858EnsemblClinVar.1
Natural variantiVAR_001038414Y → C in HPA and PKU; haplotype 4; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 3 PublicationsCorresponds to variant dbSNP:rs5030860EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi283I → C: Loss of positive cooperativity and reduction of fold-activation by L-Phe preincubation. 1 Publication1

Keywords - Diseasei

Disease mutation, Phenylketonuria

Organism-specific databases

DisGeNET

More...
DisGeNETi
5053

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
PAH

MalaCards human disease database

More...
MalaCardsi
PAH
MIMi261600 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000171759

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
79254 Classic phenylketonuria
2209 Maternal phenylketonuria
79651 Mild hyperphenylalaninemia
79253 Mild phenylketonuria
293284 Tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA32911

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL3076

Drug and drug target database

More...
DrugBanki
DB03673 Beta(2-Thienyl)Alanine
DB06262 Droxidopa
DB00668 Epinephrine
DB00120 L-Phenylalanine
DB00368 Norepinephrine
DB04419 Norleucine
DB00360 Sapropterin

IUPHAR/BPS Guide to PHARMACOLOGY

More...
GuidetoPHARMACOLOGYi
1240

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
PAH

Domain mapping of disease mutations (DMDM)

More...
DMDMi
129973

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002055481 – 452Phenylalanine-4-hydroxylaseAdd BLAST452

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei16Phosphoserine; by PKACombined sources1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
P00439

MaxQB - The MaxQuant DataBase

More...
MaxQBi
P00439

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P00439

PeptideAtlas

More...
PeptideAtlasi
P00439

PRoteomics IDEntifications database

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PRIDEi
P00439

ProteomicsDB human proteome resource

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ProteomicsDBi
51249

2D gel databases

University College Dublin 2-DE Proteome Database

More...
UCD-2DPAGEi
P00439

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P00439

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P00439

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000171759 Expressed in 108 organ(s), highest expression level in nephron tubule

CleanEx database of gene expression profiles

More...
CleanExi
HS_PAH

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
P00439 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
P00439 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA028407
HPA031642

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer and homotetramer.1 Publication

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
111090, 4 interactors

Database of interacting proteins

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DIPi
DIP-58927N

Protein interaction database and analysis system

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IntActi
P00439, 3 interactors

Molecular INTeraction database

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MINTi
P00439

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000448059

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
P00439

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1452
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DMWX-ray2.00A118-424[»]
1J8TX-ray1.70A103-427[»]
1J8UX-ray1.50A103-427[»]
1KW0X-ray2.50A103-427[»]
1LRMX-ray2.10A103-427[»]
1MMKX-ray2.00A103-427[»]
1MMTX-ray2.00A103-427[»]
1PAHX-ray2.00A117-424[»]
1TDWX-ray2.10A117-424[»]
1TG2X-ray2.20A117-424[»]
2PAHX-ray3.10A/B118-452[»]
3PAHX-ray2.00A117-424[»]
4ANPX-ray2.11A104-427[»]
4PAHX-ray2.00A117-424[»]
5FIIX-ray1.80A/B/C/D19-118[»]
5PAHX-ray2.10A117-424[»]
6PAHX-ray2.15A117-424[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P00439

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P00439

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P00439

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini36 – 114ACTPROSITE-ProRule annotationAdd BLAST79

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG3820 Eukaryota
COG3186 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000155802

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000233373

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG006841

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P00439

KEGG Orthology (KO)

More...
KOi
K00500

Identification of Orthologs from Complete Genome Data

More...
OMAi
YEFFVEC

Database of Orthologous Groups

More...
OrthoDBi
1253228at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P00439

TreeFam database of animal gene trees

More...
TreeFami
TF313327

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.10.800.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR002912 ACT_dom
IPR001273 ArAA_hydroxylase
IPR018301 ArAA_hydroxylase_Fe/CU_BS
IPR036951 ArAA_hydroxylase_sf
IPR036329 Aro-AA_hydroxylase_C_sf
IPR019774 Aromatic-AA_hydroxylase_C
IPR005961 Phe-4-hydroxylase_tetra
IPR019773 Tyrosine_3-monooxygenase-like

The PANTHER Classification System

More...
PANTHERi
PTHR11473 PTHR11473, 1 hit

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF01842 ACT, 1 hit
PF00351 Biopterin_H, 1 hit

PIRSF; a whole-protein classification database

More...
PIRSFi
PIRSF000336 TH, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR00372 FYWHYDRXLASE

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF56534 SSF56534, 1 hit

TIGRFAMs; a protein family database

More...
TIGRFAMsi
TIGR01268 Phe4hydrox_tetr, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS51671 ACT, 1 hit
PS00367 BH4_AAA_HYDROXYL_1, 1 hit
PS51410 BH4_AAA_HYDROXYL_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

P00439-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSTAVLENPG LGRKLSDFGQ ETSYIEDNCN QNGAISLIFS LKEEVGALAK
60 70 80 90 100
VLRLFEENDV NLTHIESRPS RLKKDEYEFF THLDKRSLPA LTNIIKILRH
110 120 130 140 150
DIGATVHELS RDKKKDTVPW FPRTIQELDR FANQILSYGA ELDADHPGFK
160 170 180 190 200
DPVYRARRKQ FADIAYNYRH GQPIPRVEYM EEEKKTWGTV FKTLKSLYKT
210 220 230 240 250
HACYEYNHIF PLLEKYCGFH EDNIPQLEDV SQFLQTCTGF RLRPVAGLLS
260 270 280 290 300
SRDFLGGLAF RVFHCTQYIR HGSKPMYTPE PDICHELLGH VPLFSDRSFA
310 320 330 340 350
QFSQEIGLAS LGAPDEYIEK LATIYWFTVE FGLCKQGDSI KAYGAGLLSS
360 370 380 390 400
FGELQYCLSE KPKLLPLELE KTAIQNYTVT EFQPLYYVAE SFNDAKEKVR
410 420 430 440 450
NFAATIPRPF SVRYDPYTQR IEVLDNTQQL KILADSINSE IGILCSALQK

IK
Length:452
Mass (Da):51,862
Last modified:July 21, 1986 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i018F00EBBBDDCE2F
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KND8J3KND8_HUMAN
Phenylalanine-4-hydroxylase
PAH
447Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8W1D4F8W1D4_HUMAN
Phenylalanine-4-hydroxylase
PAH
117Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8W0A0F8W0A0_HUMAN
Phenylalanine-4-hydroxylase
PAH
136Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A0U1RQY4A0A0U1RQY4_HUMAN
Phenylalanine-4-hydroxylase
PAH
143Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A0U1RQI3A0A0U1RQI3_HUMAN
Phenylalanine-4-hydroxylase
PAH
149Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti183E → G in AAH26251 (PubMed:15489334).Curated1

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

The Glu-274 variant occurs on approximately 4% of African-American PAH alleles. The enzyme activity of the variant protein is indistinguishable from that of the wild-type form.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00086916S → P in PKU. Corresponds to variant dbSNP:rs62642946EnsemblClinVar.1
Natural variantiVAR_00923920Q → L in HPA. Corresponds to variant dbSNP:rs199475662EnsemblClinVar.1
Natural variantiVAR_00087039F → L in HPA and PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62642926EnsemblClinVar.1
Natural variantiVAR_00087139Missing in PKU; haplotypes 9,21. 2 Publications1
Natural variantiVAR_00087240S → L in PKU. 1 PublicationCorresponds to variant dbSNP:rs62642938EnsemblClinVar.1
Natural variantiVAR_00087341L → F in PKU. Corresponds to variant dbSNP:rs62642928EnsemblClinVar.1
Natural variantiVAR_00924041L → P in PKU; mild. Corresponds to variant dbSNP:rs62642916EnsemblClinVar.1
Natural variantiVAR_00087442K → I in PKU; haplotype 21. Corresponds to variant dbSNP:rs62635346EnsemblClinVar.1
Natural variantiVAR_06799445V → A in PKU. 1 Publication1
Natural variantiVAR_00087546G → S in PKU; haplotype 5; significantly reduces phenylalanine binding. 1 PublicationCorresponds to variant dbSNP:rs74603784EnsemblClinVar.1
Natural variantiVAR_00087647A → V in non-PKU HPA; haplotype 4; significantly reduces phenylalanine binding. 1 PublicationCorresponds to variant dbSNP:rs118203925EnsemblClinVar.1
Natural variantiVAR_00087748L → S in PKU; mild; haplotypes 3,4. 5 PublicationsCorresponds to variant dbSNP:rs5030841EnsemblClinVar.1
Natural variantiVAR_00087853R → H in PKU. 1 PublicationCorresponds to variant dbSNP:rs118092776EnsemblClinVar.1
Natural variantiVAR_00087955F → L in HPA and PKU; does not affect oligomerization; results in loss of substrate activation. 3 PublicationsCorresponds to variant dbSNP:rs199475598EnsemblClinVar.1
Natural variantiVAR_00088056E → D in PKU; haplotype 10. Corresponds to variant dbSNP:rs199475567EnsemblClinVar.1
Natural variantiVAR_06799561N → D in PKU. 1 PublicationCorresponds to variant dbSNP:rs199475651EnsemblClinVar.1
Natural variantiVAR_06799662L → P in PKU. 1 Publication1
Natural variantiVAR_00088163 – 64TH → PN in PKU; haplotype 1; abolishes phenylalanine binding. 2
Natural variantiVAR_00088265I → N in PKU. 1 PublicationCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_06799765I → S in PKU; results in disturbed oligomerization; results in loss of substrate activation. 2 PublicationsCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_00088365I → T in PKU; haplotypes 1,5,9,21,B; abolishes phenylalanine binding. 3 PublicationsCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_06799865I → V in HPA and PKU. 2 PublicationsCorresponds to variant dbSNP:rs199475643EnsemblClinVar.1
Natural variantiVAR_00088467S → P in PKU; haplotype 4. Corresponds to variant dbSNP:rs5030842EnsemblClinVar.1
Natural variantiVAR_00088568R → S in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs76394784EnsemblClinVar.1
Natural variantiVAR_00088676E → A in PKU. Corresponds to variant dbSNP:rs62507347EnsemblClinVar.1
Natural variantiVAR_06799976E → G in non-PKU HPA. 1 PublicationCorresponds to variant dbSNP:rs62507347EnsemblClinVar.1
Natural variantiVAR_00088784D → Y in PKU; haplotype 4. Corresponds to variant dbSNP:rs62514902EnsemblClinVar.1
Natural variantiVAR_00088887S → R in non-PKU HPA; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62516151EnsemblClinVar.1
Natural variantiVAR_00088992T → I in PKU. Corresponds to variant dbSNP:rs62514903EnsemblClinVar.1
Natural variantiVAR_00089094Missing in PKU; mild; haplotype 2. 1 Publication1
Natural variantiVAR_00089198L → S in non-PKU HPA. 1 PublicationCorresponds to variant dbSNP:rs62517167EnsemblClinVar.1
Natural variantiVAR_000892104A → D in PKU; mild; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62642929EnsemblClinVar.1
Natural variantiVAR_009241110S → C in HPA. 1
Natural variantiVAR_069776121F → L in HPA. 1 Publication1
Natural variantiVAR_000893124T → I in PKU; haplotype 28. Corresponds to variant dbSNP:rs199475571EnsemblClinVar.1
Natural variantiVAR_000894129D → Y in PKU. Corresponds to variant dbSNP:rs199475606EnsemblClinVar.1
Natural variantiVAR_000895143D → G in PKU; haplotype 11. 1 PublicationCorresponds to variant dbSNP:rs199475572EnsemblClinVar.1
Natural variantiVAR_011566145D → V in PKU. Corresponds to variant dbSNP:rs140175796EnsemblClinVar.1
Natural variantiVAR_000896146H → Y in PKU. Corresponds to variant dbSNP:rs199475599EnsemblClinVar.1
Natural variantiVAR_000897148G → S in PKU; haplotypes 1,2,7. Corresponds to variant dbSNP:rs80297647EnsemblClinVar.1
Natural variantiVAR_000898151D → H in PKU; haplotypes 1,8. Corresponds to variant dbSNP:rs199475597EnsemblClinVar.1
Natural variantiVAR_000899154Y → N in PKU. Corresponds to variant dbSNP:rs199475587EnsemblClinVar.1
Natural variantiVAR_009242155R → P in PKU. Corresponds to variant dbSNP:rs199475663EnsemblClinVar.1
Natural variantiVAR_000900157R → N in PKU; severe; 5% activity; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_068000157R → S in PKU. 1 PublicationCorresponds to variant dbSNP:rs199475612EnsemblClinVar.1
Natural variantiVAR_000901158R → Q in PKU; haplotypes 1,2,4,7,16, 28. 3 PublicationsCorresponds to variant dbSNP:rs5030843EnsemblClinVar.1
Natural variantiVAR_000902158R → W in PKU. Corresponds to variant dbSNP:rs75166491EnsemblClinVar.1
Natural variantiVAR_000903160Q → P in PKU. Corresponds to variant dbSNP:rs199475601EnsemblClinVar.1
Natural variantiVAR_000904161F → S in PKU; haplotype 4. Corresponds to variant dbSNP:rs79635844EnsemblClinVar.1
Natural variantiVAR_000905164I → T in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs199475595EnsemblClinVar.1
Natural variantiVAR_000906167N → I in PKU. 1 PublicationCorresponds to variant dbSNP:rs77554925EnsemblClinVar.1
Natural variantiVAR_011567167N → S in HPA. Corresponds to variant dbSNP:rs77554925EnsemblClinVar.1
Natural variantiVAR_011568169R → H in PKU. Corresponds to variant dbSNP:rs199475679EnsemblClinVar.1
Natural variantiVAR_011569170H → D in HPA. Corresponds to variant dbSNP:rs199475655EnsemblClinVar.1
Natural variantiVAR_068001170H → Q in PKU; does not affect oligomerization. 2 PublicationsCorresponds to variant dbSNP:rs199475652EnsemblClinVar.1
Natural variantiVAR_000907170H → R in PKU. Corresponds to variant dbSNP:rs199475573EnsemblClinVar.1
Natural variantiVAR_000908171G → A in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs199475596EnsemblClinVar.1
Natural variantiVAR_000909171G → R in PKU. Corresponds to variant dbSNP:rs199475613EnsemblClinVar.1
Natural variantiVAR_000910173P → T in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475574EnsemblClinVar.1
Natural variantiVAR_000911174I → T in PKU; haplotype 1. Corresponds to variant dbSNP:rs138809906EnsemblClinVar.1
Natural variantiVAR_011570174I → V in PKU. Corresponds to variant dbSNP:rs199475632EnsemblClinVar.1
Natural variantiVAR_000912175P → A in PKU. Corresponds to variant dbSNP:rs199475604EnsemblClinVar.1
Natural variantiVAR_000913176R → L in non-PKU HPA. 1 PublicationCorresponds to variant dbSNP:rs74486803EnsemblClinVar.1
Natural variantiVAR_000914176R → P in PKU. Corresponds to variant dbSNP:rs74486803EnsemblClinVar.1
Natural variantiVAR_000915177V → L in PKU; haplotype 6. 1 PublicationCorresponds to variant dbSNP:rs199475602EnsemblClinVar.1
Natural variantiVAR_068002177V → M in HPA. 1 PublicationCorresponds to variant dbSNP:rs199475602EnsemblClinVar.1
Natural variantiVAR_000916178E → G in non-PKU HPA. 1 PublicationCorresponds to variant dbSNP:rs77958223EnsemblClinVar.1
Natural variantiVAR_009243