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 but with lower specificity (PubMed:10933781, PubMed:11922614). Positively regulates the regression of retinal hyaloid vessels during postnatal development (By similarity).
Catecholamine biosynthesis; dopamine biosynthesis; dopamine from L-tyrosine: step 1/2.
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 (PubMed:21392500). 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 (PubMed:11502746, PubMed:1672315).
Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
Tyrosine 3-monooxygenase, Tyrosine 3-hydroxylase, TH
Proteins
Neuroscience
55966Da
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