TH
entrez
7054
canonical
uniprot
P07101
canonical
ensembl
ENSG00000180176
resolver
ensp
ENSP00000325951
resolver
ensp
ENSP00000328814
resolver
ensp
ENSP00000370567
resolver
ensp
ENSP00000370571
resolver
ensp
ENSP00000523176
resolver
genesymbol
TH
resolver
genesymbol_syn
TYH
resolver
hgnc
HGNC:11782
resolver
uniprot
B7ZL70
resolver
uniprot
B7ZL73
resolver
uniprot
P78428
resolver
uniprot
Q0PWM2
resolver
uniprot
Q0PWM3
resolver
uniprot
Q15585
resolver
uniprot
Q15588
resolver
uniprot
Q15589
resolver
uniprot
Q2M3B4
resolver
uniprot_entry
P78428_HUMAN
resolver
uniprot_entry
TY3H_HUMAN
resolver
uniprot_sec
B7ZL70
resolver
uniprot_sec
B7ZL73
resolver
uniprot_sec
Q0PWM2
resolver
uniprot_sec
Q0PWM3
resolver
uniprot_sec
Q15585
resolver
uniprot_sec
Q15588
resolver
uniprot_sec
Q15589
resolver
uniprot_sec
Q2M3B4
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited in feedback fashion by the catecholamine neurotransmitters, especially by dopamine in competition with tetrahydrobiopterin (PubMed:15287903). Phosphorylation of several Ser/Thr residues in the N-terminus regulates the catalytic activity (PubMed:1680128, PubMed:7901013). Ser-62 and Ser-71 are readily phosphorylated to activate the catalytic activity (PubMed:1680128, PubMed:7901013). A Cysteine modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-monooxygenase activity through the modification of the Cys-207 (PubMed:34922205). {ECO:0000269|PubMed:15287903, ECO:0000269|PubMed:1680128, ECO:0000269|PubMed:34922205, ECO:0000269|PubMed:7901013}.
uniprot
proteins
amino_acid_sequence
MPTPDATTPQAKGFRRAVSELDAKQAEAIMVRGQGAPGPSLTGSPWPGTAAPAASYTPTPRSPRFIGRRQSLIEDARKEREAAVAAAAAAVPSEPGDPLEAVAFEEKEGKAVLNLLFSPRATKPSALSRAVKVFETFEAKIHHLETRPAQRPRAGGPHLEYFVRLEVRRGDLAALLSGVRQVSEDVRSPAGPKVPWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQVYRQRRKLIAEIAFQYRHGDPIPRVEYTAEEIATWKEVYTTLKGLYATHACGEHLEAFALLERFSGYREDNIPQLEDVSRFLKERTGFQLRPVAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPDCCHELLGHVPMLADRTFAQFSQDIGLASLGASDEEIEKLSTLYWFTVEFGLCKQNGEVKAYGAGLLSSYGELLHCLSEEPEIRAFDPEAAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYASRIQRPFSVKFDPYTLAIDVLDSPQAVRRSLEGVQDELDTLAHALSAIG
uniprot
proteins
disease_involvement
DISEASE: Segawa syndrome autosomal recessive (ARSEGS) [MIM:605407]: 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. {ECO:0000269|PubMed:10585338, ECO:0000269|PubMed:11196107, ECO:0000269|PubMed:11246459, ECO:0000269|PubMed:15505183, ECO:0000269|PubMed:15747353, ECO:0000269|PubMed:16049992, ECO:0000269|PubMed:17696123, ECO:0000269|PubMed:18058633, ECO:0000269|PubMed:18554280, ECO:0000269|PubMed:19491146, ECO:0000269|PubMed:20056467, ECO:0000269|PubMed:20430833, ECO:0000269|PubMed:21940685, ECO:0000269|PubMed:22264700, ECO:0000269|PubMed:22815559, ECO:0000269|PubMed:23762320, ECO:0000269|PubMed:23939262, ECO:0000269|PubMed:24753243, ECO:0000269|PubMed:7814018, ECO:0000269|PubMed:8528210, ECO:0000269|PubMed:8817341, ECO:0000269|PubMed:9613851, ECO:0000269|PubMed:9703425}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=May play a role in the pathogenesis of Parkinson disease (PD). A genome-wide copy number variation analysis has identified a 34 kilobase deletion over the TH gene in a PD patient but not in any controls. {ECO:0000269|PubMed:20809526}.
uniprot
proteins
ec_number
1.14.16.2
uniprot
proteins
function
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 (PubMed:15287903, PubMed:1680128, PubMed:17391063, PubMed:24753243, PubMed:34922205, PubMed:8528210, Ref.18). 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). {ECO:0000250|UniProtKB:P04177, ECO:0000250|UniProtKB:P24529, ECO:0000269|PubMed:15287903, ECO:0000269|PubMed:1680128, ECO:0000269|PubMed:17391063, ECO:0000269|PubMed:24753243, ECO:0000269|PubMed:34922205, ECO:0000269|PubMed:8528210, ECO:0000269|Ref.18}.; FUNCTION: [Isoform 5]: Lacks catalytic activity. {ECO:0000269|PubMed:17391063}.; FUNCTION: [Isoform 6]: Lacks catalytic activity. {ECO:0000269|PubMed:17391063}.
uniprot
proteins
mass_dalton
58600
uniprot
proteins
mutagenesis
MUTAGEN 62; /note="S->A: Affects subcellular localization. Accumulates mainly in the soma of the neuroblastoma cells."; /evidence="ECO:0000269|PubMed:28637871"; MUTAGEN 62; /note="S->E: Does not affect subcellular localization. Distributed throughout the soma and neurites."; /evidence="ECO:0000269|PubMed:28637871"; MUTAGEN 71; /note="S->E: Suppresses feedback inhibition induced by dopamine. Suppresses feedback inhibition induced by dopamine; when associated with A-207."; /evidence="ECO:0000269|PubMed:34922205"; MUTAGEN 207; /note="C->A: Suppresses the decrease in tyrosine 3-monooxygenase activity induced by NEM modification. Suppresses feedback inhibition induced by dopamine; when associated with E-71."; /evidence="ECO:0000269|PubMed:34922205
uniprot
proteins
pathway_participation
PATHWAY: Catecholamine biosynthesis; dopamine biosynthesis; dopamine from L-tyrosine: step 1/2. {ECO:0000269|PubMed:17391063}.
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000250|UniProtKB:P04177, ECO:0000269|PubMed:15287903, ECO:0000269|PubMed:24947669, ECO:0000269|PubMed:28637871, ECO:0000269|PubMed:7901013}.
uniprot
proteins
protein_family
Biopterin-dependent aromatic amino acid hydroxylase family
uniprot
proteins
pubmed
10391209
uniprot
proteins
pubmed
10585338
uniprot
proteins
pubmed
11196107
uniprot
proteins
pubmed
11246459
uniprot
proteins
pubmed
15287903
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15505183
uniprot
proteins
pubmed
15747353
uniprot
proteins
pubmed
16049992
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
1680128
uniprot
proteins
pubmed
17391063
uniprot
proteins
pubmed
17696123
uniprot
proteins
pubmed
18058633
uniprot
proteins
pubmed
18554280
uniprot
proteins
pubmed
19491146
uniprot
proteins
pubmed
20056467
uniprot
proteins
pubmed
20430833
uniprot
proteins
pubmed
20809526
uniprot
proteins
pubmed
21940685
uniprot
proteins
pubmed
22264700
uniprot
proteins
pubmed
22815559
uniprot
proteins
pubmed
23762320
uniprot
proteins
pubmed
23939262
uniprot
proteins
pubmed
24753243
uniprot
proteins
pubmed
24947669
uniprot
proteins
pubmed
28637871
uniprot
proteins
pubmed
2882428
uniprot
proteins
pubmed
2887169
uniprot
proteins
pubmed
2888085
uniprot
proteins
pubmed
2892893
uniprot
proteins
pubmed
2896667
uniprot
proteins
pubmed
2902075
uniprot
proteins
pubmed
34922205
uniprot
proteins
pubmed
7789962
uniprot
proteins
pubmed
7814018
uniprot
proteins
pubmed
7901013
uniprot
proteins
pubmed
8528210
uniprot
proteins
pubmed
8817341
uniprot
proteins
pubmed
9613851
uniprot
proteins
pubmed
9703425
uniprot
proteins
pubmed
9754624
uniprot
proteins
sequence_length
528
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P24529}. Nucleus {ECO:0000250|UniProtKB:P04177}. Cell projection, axon {ECO:0000250|UniProtKB:P24529}. Cytoplasm {ECO:0000250|UniProtKB:P04177}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle {ECO:0000250|UniProtKB:P04177}. 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. {ECO:0000250|UniProtKB:P04177}.
uniprot
proteins