P17289 · TY3H_BOVIN
- ProteinTyrosine 3-monooxygenase
- GeneTH
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids491 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of cathecolamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to L-Dopa (By similarity).
In addition to tyrosine, is able to catalyze the hydroxylation of phenylalanine and tryptophan with lower specificity (By similarity).
Positively regulates the regression of retinal hyaloid vessels during postnatal development (By similarity).
In addition to tyrosine, is able to catalyze the hydroxylation of phenylalanine and tryptophan with lower specificity (By similarity).
Positively regulates the regression of retinal hyaloid vessels during postnatal development (By similarity).
Catalytic activity
- (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-dopaThis reaction proceeds in the forward direction.
Cofactor
Activity regulation
Inhibited in feedback fashion by the catecholamine neurotransmitters, especially by dopamine in competition with tetrahydrobiopterin. Phosphorylation of several Ser/Thr residues in the N-terminus regulates the catalytic activity. Ser-31 and Ser-40 are readily phosphorylated to activate the catalytic activity. A Cysteine modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-monooxygenase activity through the modification of the Cys-170.
Pathway
Catecholamine biosynthesis; dopamine biosynthesis; dopamine from L-tyrosine: step 1/2.
Features
Showing features for binding site, site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | axon | |
Cellular Component | cytoplasm | |
Cellular Component | nucleus | |
Cellular Component | perikaryon | |
Cellular Component | perinuclear region of cytoplasm | |
Cellular Component | synaptic vesicle | |
Molecular Function | iron ion binding | |
Molecular Function | tyrosine 3-monooxygenase activity | |
Biological Process | dopamine biosynthetic process from tyrosine | |
Biological Process | heart development | |
Biological Process | hyaloid vascular plexus regression | |
Biological Process | response to ethanol | |
Biological Process | response to hypoxia |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosine 3-monooxygenase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionP17289
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: When phosphorylated at Ser-19 shows a nuclear distribution and when phosphorylated at Ser-31 as well at Ser-40 shows a cytosolic distribution (By similarity).
Expressed in dopaminergic axons and axon terminals (By similarity).
Expressed in dopaminergic axons and axon terminals (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Chain | PRO_0000205560 | 2-491 | Tyrosine 3-monooxygenase | |||
Sequence: PTPNAASPQAKGFRRAVSELDAKQAEAIMSPRFVGRRQSLIQDARKEREKAEAAASSSESAEAAAWLERDGEAVLTLLFALPPTRPPALTRAIKVFETFEAHLHHLETRPAQPLRAGSPPLECFVRCEVPGPVVPALLSALRRVAEDVRAAGESKVLWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQAYRQRRKLIAEIAFQYKQGDPIPHVEYTAEETATWKEVYSTLRGLYPTHACREHLEAFELLERFCGYREDRIPQLEDVSRFLKERTGFQLRPAAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPECCHELLGHVPMLADRTFAQFSQDIGLASLGVSDEEIEKLSTLYWFTVEFGLCKQNGEVKAYGAGLLSSYGELLHSLSEEPEIRAFDPDAAAVQPYQDQTYQPVYFVSESFSDAKDKLRSYASRIQRPFSVKFDPYTLAIDVLDSPHAIRHALDGVQDEMQALAHALNAIS | ||||||
Modified residue | 19 | Phosphoserine; by CaMK2 | ||||
Sequence: S | ||||||
Modified residue | 31 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 40 | Phosphoserine; by CaMK2 and PKA | ||||
Sequence: S | ||||||
Modified residue | 465 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated on Ser-19, Ser-31 and Ser-40 by several protein kinases with different site specificities. Phosphorylation at Ser-31 and Ser-40 leads to an increase of TH activity. Phosphorylation at Ser-40 activates the enzyme and also counteracts the feedback inhibition of TH by catecholamines (By similarity).
Phosphorylation of Ser-19 and Ser-31 triggers the proteasomal degradation of TH through the ubiquitin-proteasome pathway (By similarity).
Phosphorylation at Ser-31 facilitates transport of TH from the soma to the nerve terminals via the microtubule network (By similarity).
Phosphorylation at Ser-19 induces the high-affinity binding to the 14-3-3 protein YWHAG; this interaction may influence the phosphorylation and dephosphorylation of other sites (By similarity).
Ser-19 increases the phosphorylation at Ser-40 in a hierarchical manner, leading to increased activity (By similarity).
Phosphorylation of Ser-19 and Ser-31 triggers the proteasomal degradation of TH through the ubiquitin-proteasome pathway (By similarity).
Phosphorylation at Ser-31 facilitates transport of TH from the soma to the nerve terminals via the microtubule network (By similarity).
Phosphorylation at Ser-19 induces the high-affinity binding to the 14-3-3 protein YWHAG; this interaction may influence the phosphorylation and dephosphorylation of other sites (By similarity).
Ser-19 increases the phosphorylation at Ser-40 in a hierarchical manner, leading to increased activity (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Structure
Sequence
- Sequence statusComplete
- Length491
- Mass (Da)55,123
- Last updated2007-01-23 v5
- Checksum86707712238F12F2
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 65-68 | in Ref. 2; AAA30798 | ||||
Sequence: AAWL → GSLV | ||||||
Sequence conflict | 73 | in Ref. 2; AAA30798 | ||||
Sequence: E → K | ||||||
Sequence conflict | 83 | in Ref. 2; AAA30798 | ||||
Sequence: P → R | ||||||
Sequence conflict | 86 | in Ref. 2; AAA30798 | ||||
Sequence: R → K | ||||||
Sequence conflict | 284 | in Ref. 2; AAA30798 | ||||
Sequence: A → V | ||||||
Sequence conflict | 321 | in Ref. 2; AAA30798 | ||||
Sequence: E → D | ||||||
Sequence conflict | 328-330 | in Ref. 2; AAA30798 | ||||
Sequence: GHV → AHG | ||||||
Sequence conflict | 380 | in Ref. 2; AAA30798 | ||||
Sequence: K → N | ||||||
Sequence conflict | 471 | in Ref. 2; AAA30798 | ||||
Sequence: H → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M36794 EMBL· GenBank· DDBJ | AAA30779.1 EMBL· GenBank· DDBJ | mRNA | ||
M36705 EMBL· GenBank· DDBJ | AAA30798.1 EMBL· GenBank· DDBJ | mRNA |