TH

The protein encoded by this gene is involved in the conversion of tyrosine to dopamine. It is the rate-limiting enzyme in the synthesis of catecholamines, hence plays a key role in the physiology of adrenergic neurons. Mutations in this gene have been associated with autosomal recessive Segawa syndrome. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

TH Tyrosine Hydroxylase

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 (PubMed:17391063, PubMed:1680128, PubMed:15287903, PubMed:8528210, Ref.18, PubMed:34922205, PubMed:24753243).
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).
Isoform 5
Lacks catalytic activity.
Isoform 6
Lacks catalytic activity.

Aminergic neurotransmitter loading into synaptic vesicleIEA:Ensembl
Anatomical structure morphogenesisManual Assertion Based On ExperimentTAS:ProtInc
Animal organ morphogenesisISS:BHF-UCL
Cellular response to alkaloidIEA:Ensembl
Cellular response to glucose stimulusIEA:Ensembl
Cellular response to growth factor stimulusIEA:Ensembl
Cellular response to manganese ionIEA:Ensembl
Cellular response to nicotineIEA:Ensembl
Cellular response to xenobiotic stimulusIEA:Ensembl
Cerebral cortex developmentIEA:Ensembl
Circadian sleep/wake cycleIEA:Ensembl
Dopamine biosynthetic processManual Assertion Based On ExperimentIDA:BHF-UCL
Dopamine biosynthetic process from tyrosineManual Assertion Based On ExperimentIBA:GO_Central
Eating behaviorIEA:Ensembl
Embryonic camera-type eye morphogenesisISS:BHF-UCL
Epinephrine biosynthetic processManual Assertion Based On ExperimentIDA:BHF-UCL
Eye photoreceptor cell developmentISS:BHF-UCL
Fatty acid metabolic processIEA:Ensembl
Glycoside metabolic processIEA:Ensembl
Heart developmentISS:BHF-UCL
Heart morphogenesis1 PublicationNAS:BHF-UCL
Hyaloid vascular plexus regressionISS:UniProtKB
Isoquinoline alkaloid metabolic processIEA:Ensembl
LearningISS:BHF-UCL
Locomotory behaviorISS:BHF-UCL
Mating behaviorIEA:Ensembl
MemoryISS:BHF-UCL
Multicellular organism agingIEA:Ensembl
Neurotransmitter biosynthetic processIEA:UniProtKB-KW
Norepinephrine biosynthetic processManual Assertion Based On ExperimentIDA:BHF-UCL
Phthalate metabolic processIEA:Ensembl
Phytoalexin metabolic processIEA:Ensembl
PigmentationManual Assertion Based On ExperimentTAS:BHF-UCL
Regulation of heart contractionISS:BHF-UCL
Response to activityIEA:Ensembl
Response to amphetamineIEA:Ensembl
Response to corticosteroneIEA:Ensembl
Response to electrical stimulusIEA:Ensembl
Response to estradiolIEA:Ensembl
Response to ethanolManual Assertion Based On ExperimentIDA:BHF-UCL
Response to etherIEA:Ensembl
Response to herbicideIEA:Ensembl
Response to hypoxiaManual Assertion Based On ExperimentIDA:BHF-UCL
Response to immobilization stressIEA:Ensembl
Response to isolation stressIEA:Ensembl
Response to light stimulusIEA:Ensembl
Response to lipopolysaccharideIEA:Ensembl
Response to nutrient levelsIEA:Ensembl
Response to peptide hormoneIEA:Ensembl
Response to pyrethroidIEA:Ensembl
Response to salt stressIEA:Ensembl
Response to water deprivationIEA:Ensembl
Response to zinc ionIEA:Ensembl
Sensory perception of soundIEA:Ensembl
Social behaviorIEA:Ensembl
Sphingolipid metabolic processIEA:Ensembl
Synaptic transmission, dopaminergicISS:BHF-UCL
Terpene metabolic processIEA:Ensembl
Visual perceptionISS:BHF-UCL

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 at Ser-40 shows a cytosolic distribution (By similarity).
Expressed in dopaminergic axons and axon terminals.

Segawa syndrome autosomal recessive (ARSEGS):
A form of DOPA-responsive dystonia presenting in infancy or early childhood. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Some cases present with parkinsonian symptoms in infancy. Unlike all other forms of dystonia, it is an eminently treatable condition, due to a favorable response to L-DOPA.

Phosphorylated on Ser-19, Ser-62 and Ser-71 by several protein kinases with different site specificities. Phosphorylation at Ser-62 and Ser-71 leads to an increase of TH activity (PubMed:7901013).
Phosphorylation at Ser-71 activates the enzyme and also counteracts the feedback inhibition of TH by catecholamines (PubMed:15287903).
Phosphorylation of Ser-19 and Ser-62 triggers the proteasomal degradation of TH through the ubiquitin-proteasome pathway (By similarity).
Phosphorylation at Ser-62 facilitates transport of TH from the soma to the nerve terminals via the microtubule network (PubMed:28637871).
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 (PubMed:24947669).
Ser-19 increases the phosphorylation at Ser-71 in a hierarchical manner, leading to increased activity (By similarity).