Th
Developmental stage
Expressed in the retinal inner nuclear layer and outer nuclear layer at postnatal day 8 (P8) (PubMed:30936473). Expressed in retinal dopaminergic amacrine cells in the retina at P8 and P15 (PubMed:30936473).
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 (PubMed:30936473).
Pathway
Catecholamine biosynthesis; dopamine biosynthesis; dopamine from L-tyrosine: step 1/2.
Post-translational modifications
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).
Sequence Similarities
Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
Tissue Specificity
Expressed in the adrenal gland (PubMed:1674869). Expressed in the retina (PubMed:30936473). Expressed in the in the striatum (at protein level) (PubMed:17296554).
Cellular localization
- Cytoplasm
- Perinuclear region
- Nucleus
- Cell projection
- Axon
- Cytoplasm
- Cytoplasmic vesicle
- Secretory vesicle
- Synaptic vesicle
- When phosphorylated at Ser-19 shows a nuclear distribution and when phosphorylated at Ser-31 as well as at Ser-40 shows a cytosolic distribution (By similarity). Expressed in dopaminergic axons and axon terminals (PubMed:17296554).
Alternative names
Tyrosine 3-monooxygenase, Tyrosine 3-hydroxylase, TH, Th