P90925 · PH4H_CAEEL
- ProteinPhenylalanine-4-hydroxylase
- Genepah-1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids457 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine (PubMed:10928216, PubMed:18460651).
Catalyzes the hydroxylation of tryptophan to 5-hydroxy-L-tryptophan (PubMed:10928216).
Plays a role in the biosynthesis of a melanin-like cuticle pigment (PubMed:18460651).
Catalyzes the hydroxylation of tryptophan to 5-hydroxy-L-tryptophan (PubMed:10928216).
Plays a role in the biosynthesis of a melanin-like cuticle pigment (PubMed:18460651).
Catalytic activity
- (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-phenylalanine + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine
Cofactor
Activity regulation
Inhibited by tetrahydrobiopterin. Unlike its mammalian orthologs, pah-1 does not exhibit allosteric binding behavior for phenylalanine.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
146 μM | L-phenylalanine | 25 | ||||
33 μM | tetrahydrobiopterin (BH4) | 25 |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
3.3 μmol/min/mg | 25 | towards L-phenylalanine | |||
3.22 μmol/min/mg | 25 | towards tetrahydrobiopterin (BH4) |
Pathway
Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 1/6.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Molecular Function | iron ion binding | |
Molecular Function | phenylalanine 4-monooxygenase activity | |
Molecular Function | tryptophan 5-monooxygenase activity | |
Biological Process | collagen and cuticulin-based cuticle development | |
Biological Process | determination of adult lifespan | |
Biological Process | L-phenylalanine catabolic process | |
Biological Process | melanin biosynthetic process | |
Biological Process | reproductive process | |
Biological Process | response to oxidative stress | |
Biological Process | tryptophan catabolic process | |
Biological Process | tyrosine biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePhenylalanine-4-hydroxylase
- EC number
- Short namesPAH
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Nematoda > Chromadorea > Rhabditida > Rhabditina > Rhabditomorpha > Rhabditoidea > Rhabditidae > Peloderinae > Caenorhabditis
Accessions
- Primary accessionP90925
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Reduced L-phenylalanine hydroxylation. Lack of a yellow-orange pheomelanine-like pigment in the cuticle. Higher cuticle resistance to physical or chemical disintegration factors or oxidizing environments. Increase in superoxide dismutase activity. Increased life span. In a bli-3(e767) mutant background, growth arrest in early larval development, severe cuticle abnormalities with large blisters and increased superoxide dismutase activity. RNAi-mediated knockdown together with fah-1 RNAi partially rescues the impaired growth and fertility defects in the single fah-1 RNAi mutant (PubMed:18227072).
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000205551 | 1-457 | Phenylalanine-4-hydroxylase | |||
Sequence: MPPAGQDDLDFLKYAMESYVADVNADIGKTTIVFTLREKAGALAETLKLFQAHDVNLSHIESRPSKTHEGCYEVLVEFAEAEDHRKIEGVIEHFQQKAEKKVLVQDWNTKNKQNKDSVPWFPQKINDIDQFANRILSYGAELDADHPGFKDMTYRERRKFFADIAFNFKHGDKIPTITYTDEEIATWRTVYNELTVMYPKNACQEFNYIFPLLQQNCGFGPDRIPQLQDVSDFLKDCTGYTIRPVAGLLSSRDFLAGLAFRVFHSTQYIRHHSAPKYTPEPDICHELLGHVPLFADVEFAQFSQEIGLASLGAPDDVIEKLATLYWFTIEFGICQQDGEKKAYGAGLLSSFGELQYALSDKPEVVDFDPAVCCVTKYPITEYQPKYFLAESFASAKNKLKSWAATINRPFQIRYNAYTQRVEILDKVAALQRLARDIRSDISTLEEALGKVNNLKMK |
Proteomic databases
Expression
Tissue specificity
Expressed in the seam cells of the lateral hypodermis, in the ventral hypodermis and in the hyp7 hypodermal syncytium, in hypodermal cells in the tail and in body wall muscle cells (at protein level).
Developmental stage
Expressed during all larval stages and in adult animals (at protein level).
Gene expression databases
Interaction
Subunit
Homotetramer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P90925 | rps-10 O01869 | 3 | EBI-318020, EBI-314419 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 31-108 | ACT | ||||
Sequence: TIVFTLREKAGALAETLKLFQAHDVNLSHIESRPSKTHEGCYEVLVEFAEAEDHRKIEGVIEHFQQKAEKKVLVQDWN |
Sequence similarities
Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P90925-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Namea
- Length457
- Mass (Da)52,129
- Last updated2000-05-30 v2
- Checksum68365836DFEC8D4F
P90925-2
- Nameb
- Differences from canonical
- 1-12: MPPAGQDDLDFL → MNIDEIRK
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_059801 | 1-12 | in isoform b | |||
Sequence: MPPAGQDDLDFL → MNIDEIRK | ||||||
Sequence conflict | 251 | in Ref. 1; AAD31643 | ||||
Sequence: S → P | ||||||
Sequence conflict | 258 | in Ref. 1; AAD31643 | ||||
Sequence: L → W |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF119388 EMBL· GenBank· DDBJ | AAD31643.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
Z66497 EMBL· GenBank· DDBJ | CAA91286.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BX284602 EMBL· GenBank· DDBJ | CCH63805.1 EMBL· GenBank· DDBJ | Genomic DNA |