Tyrosine 3-monooxygenase

Function

Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of catecholamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to L-Dopa. 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).

Classification

Family (Pfam)

PF00351 Biopterin_H, PF21417 TH_ACT, PF12549 TOH_N

InterPro

ACT-like_dom_sf, ArAA_hydroxylase, ArAA_hydroxylase_Fe/CU_BS, ArAA_hydroxylase_sf, Aro-AA_hydroxylase_C_sf, Aromatic-AA_hydroxylase_C, Eu_TyrOH_cat, TH_ACT, Tyr_3_mOase, Tyrosine_3-monooxygenase-like, Tyrosine_hydroxylase_CS

Functional cluster

Oxidoreductases, Catalases & Peroxidases

Experimental structures · PDB · 7

• 2XSN X-ray 2.68A
• 4J6S X-ray 3.08A
• 6ZN2 EM 4.30A
• 6ZVP EM 4.00A
• 6ZZU EM 3.50A
• 7A2G EM 4.10A
• 7PIM EM 4.60A

A predicted model is available from AlphaFold.

Gene Ontology · 39

• GO:0030424 axon
• GO:0005737 cytoplasm
• GO:0009898 cytoplasmic side of plasma membrane
• GO:0031410 cytoplasmic vesicle
• GO:0005829 cytosol
• GO:0033162 melanosome membrane
• GO:0043005 neuron projection
• GO:0005634 nucleus
• GO:0043204 perikaryon
• GO:0048471 perinuclear region of cytoplasm
• GO:0005790 smooth endoplasmic reticulum
• GO:0008021 synaptic vesicle
• GO:0019899 enzyme binding
• GO:0042802 identical protein binding
• GO:0005506 iron ion binding
• GO:0004511 tyrosine 3-monooxygenase activity
• GO:0009653 anatomical structure morphogenesis
• GO:0009887 animal organ morphogenesis
• GO:0050890 cognition
• GO:0042416 dopamine biosynthetic process
• GO:0006585 dopamine biosynthetic process from tyrosine
• GO:0048596 embryonic camera-type eye morphogenesis
• GO:0042418 epinephrine biosynthetic process
• GO:0042462 eye photoreceptor cell development
• GO:0007507 heart development
• GO:0003007 heart morphogenesis
• GO:1990384 hyaloid vascular plexus regression
• GO:0007612 learning
• GO:0007626 locomotory behavior
• GO:0007617 mating behavior
• GO:0007613 memory
• GO:0042421 norepinephrine biosynthetic process
• GO:0043473 pigmentation
• GO:0008016 regulation of heart contraction
• GO:0045471 response to ethanol
• GO:0001666 response to hypoxia
• GO:0042427 serotonin biosynthetic process
• GO:0001963 synaptic transmission, dopaminergic
• GO:0007601 visual perception

Disease associations

• TH-deficient dopa-responsive dystonia MONDO:0011551

Drugs targeting this protein · 1

• METYROSINE inhibitor

Related proteins · sequence + function similarity

• Tyrosine 3-monooxygenase 0.95
• Tyrosine 3-monooxygenase 0.94
• Tyrosine 3-monooxygenase 0.93
• Tyrosine 3-monooxygenase 0.91
• Tyrosine 3-monooxygenase 0.81
• Tyrosine 3-monooxygenase 0.81
• Tyrosine 3-monooxygenase 0.75
• Tyrosine 3-monooxygenase 0.74
• Phenylalanine 4-monooxygenase, chloroplastic 0.72
• Tryptophan 5-hydroxylase 2 0.68
• Tyrosine 3-monooxygenase 0.68
• Tryptophan 5-hydroxylase 1 0.67

Co-cited proteins · studied together in the literature

• GTP cyclohydrolase 1 1 shared papers

Literature · 42 cited papers

• Tyrosine hydroxylase activity is regulated through the modification of the 176th cysteine residue. Biochem. Biophys. Res. Commun. · 2022
• Phosphorylation at serine 31 targets tyrosine hydroxylase to vesicles for transport along microtubules. J. Biol. Chem. · 2017
• Phosphorylation dependence and stoichiometry of the complex formed by tyrosine hydroxylase and 14-3-3gamma. Mol. Cell. Proteomics · 2014
• Functional studies of tyrosine hydroxylase missense variants reveal distinct patterns of molecular defects in Dopa-responsive dystonia. Hum. Mutat. · 2014
• A novel compound heterozygous tyrosine hydroxylase mutation (p.R441P) with complex phenotype. J. Parkinson's Dis. · 2011
• GTP cyclohydrolase I and tyrosine hydroxylase gene mutations in familial and sporadic dopa-responsive dystonia patients. PLoS ONE · 2013
• Myoclonus-dystonia syndrome due to tyrosine hydroxylase deficiency. Neurology · 2012
• Tyrosine hydroxylase deficiency in Taiwanese infants. Pediatr. Neurol. · 2012
• A new tyrosine hydroxylase genotype associated with early-onset severe encephalopathy. J. Child Neurol. · 2012
• A rare novel deletion of the tyrosine hydroxylase gene in Parkinson disease. Hum. Mutat. · 2010
• Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis. Brain · 2010
• Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese. Mol. Genet. Metab. · 2010
• … and 30 more in the literature graph