ID  P07101;
PN  Tyrosine 3-monooxygenase;
GN  TH;
OS  9606;
SL  Nucleus Position: SL-0198;
SL  Comments: 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}.
DR  UNIPROT: P07101;
DR  UNIPROT: B7ZL70;
DR  UNIPROT: B7ZL73;
DR  UNIPROT: Q0PWM2;
DR  UNIPROT: Q0PWM3;
DR  UNIPROT: Q15585;
DR  UNIPROT: Q15588;
DR  UNIPROT: Q15589;
DR  UNIPROT: Q2M3B4;
DR  PDB: 2XSN;
DR  PDB: 4J6S;
DR  PDB: 6ZN2;
DR  PDB: 6ZVP;
DR  PDB: 6ZZU;
DR  PDB: 7A2G;
DR  PDB: 7PIM;
DR  Pfam: PF00351;
DR  Pfam: PF12549;
DR  PROSITE: PS00367;
DR  PROSITE: PS51410;
DR  OMIM: 191290;
DR  OMIM: 605407;
DR  DisGeNET: 7054;
DE  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 (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). {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}. [Isoform 5]: Lacks catalytic activity. {ECO:0000269|PubMed:17391063}. [Isoform 6]: Lacks catalytic activity. {ECO:0000269|PubMed:17391063}.
DE  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. 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}.
DE  Reference Proteome: Yes;
DE  Interaction: P68509; IntAct: EBI-7146814; Score: 0.35
DE  Interaction: P63104; IntAct: EBI-7275920; Score: 0.53
DE  Interaction: P61981; IntAct: EBI-7275933; Score: 0.35
DE  Interaction: P63103; IntAct: EBI-7846709; Score: 0.35
DE  Interaction: P07101; IntAct: EBI-24276311; Score: 0.63
DE  Interaction: P29762; IntAct: EBI-24285006; Score: 0.56
DE  Interaction: Q9UJ04; IntAct: EBI-24312149; Score: 0.56
DE  Interaction: O75928; IntAct: EBI-24482857; Score: 0.56
DE  Interaction: Q9UHX1; IntAct: EBI-24487537; Score: 0.56
DE  Interaction: Q5MCW4; IntAct: EBI-24530033; Score: 0.56
DE  Interaction: P08651; IntAct: EBI-24703454; Score: 0.56
DE  Interaction: C9J7I0; IntAct: EBI-24710004; Score: 0.56
DE  Interaction: Q99750; IntAct: EBI-24384608; Score: 0.56
DE  Interaction: P61978; IntAct: EBI-24440007; Score: 0.56
DE  Interaction: P0DJD3; IntAct: EBI-24469611; Score: 0.56
DE  Interaction: Q8NCN2; IntAct: EBI-21751771; Score: 0.35
DE  Interaction: Q9UL54; IntAct: EBI-21751771; Score: 0.35
DE  Interaction: Q9UKB3; IntAct: EBI-21751771; Score: 0.35
DE  Interaction: Q8IUW5; IntAct: EBI-21751771; Score: 0.35
DE  Interaction: Q7LBC6; IntAct: EBI-21751771; Score: 0.35
DE  Interaction: Q6P444; IntAct: EBI-21751771; Score: 0.35
DE  Interaction: Q15750; IntAct: EBI-21751771; Score: 0.35
DE  Interaction: O43318; IntAct: EBI-21751771; Score: 0.35
GO  GO:0070161;
GO  GO:0030424;
GO  GO:0005737;
GO  GO:0009898;
GO  GO:0031410;
GO  GO:0005829;
GO  GO:0030425;
GO  GO:0033162;
GO  GO:0005739;
GO  GO:0043005;
GO  GO:0005634;
GO  GO:0043204;
GO  GO:0048471;
GO  GO:0005790;
GO  GO:0008021;
GO  GO:0043195;
GO  GO:0016597;
GO  GO:0035240;
GO  GO:0019899;
GO  GO:0008199;
GO  GO:0008198;
GO  GO:0042802;
GO  GO:0019825;
GO  GO:0019904;
GO  GO:0034617;
GO  GO:0004511;
GO  GO:0015842;
GO  GO:0009653;
GO  GO:0009887;
GO  GO:0071312;
GO  GO:0071333;
GO  GO:0071363;
GO  GO:0071287;
GO  GO:0071316;
GO  GO:0071466;
GO  GO:0021987;
GO  GO:0042745;
GO  GO:0042416;
GO  GO:0006585;
GO  GO:0042755;
GO  GO:0048596;
GO  GO:0042418;
GO  GO:0042462;
GO  GO:0006631;
GO  GO:0016137;
GO  GO:0007507;
GO  GO:0003007;
GO  GO:1990384;
GO  GO:0033076;
GO  GO:0007612;
GO  GO:0007626;
GO  GO:0007617;
GO  GO:0007613;
GO  GO:0010259;
GO  GO:0042136;
GO  GO:0042421;
GO  GO:0018963;
GO  GO:0052314;
GO  GO:0043473;
GO  GO:0008016;
GO  GO:0014823;
GO  GO:0001975;
GO  GO:0051412;
GO  GO:0051602;
GO  GO:0032355;
GO  GO:0045471;
GO  GO:0045472;
GO  GO:0009635;
GO  GO:0001666;
GO  GO:0035902;
GO  GO:0035900;
GO  GO:0009416;
GO  GO:0032496;
GO  GO:0031667;
GO  GO:0043434;
GO  GO:0046684;
GO  GO:0009651;
GO  GO:0009414;
GO  GO:0010043;
GO  GO:0007605;
GO  GO:0035176;
GO  GO:0006665;
GO  GO:0001963;
GO  GO:0042214;
GO  GO:0007601;
TP  Membrane Topology: Unknown; Source: UniProt - Sequence Analysis;
SQ  MPTPDATTPQAKGFRRAVSELDAKQAEAIMVRGQGAPGPSLTGSPWPGTAAPAASYTPTPRSPRFIGRRQSLIEDARKER
SQ  EAAVAAAAAAVPSEPGDPLEAVAFEEKEGKAVLNLLFSPRATKPSALSRAVKVFETFEAKIHHLETRPAQRPRAGGPHLE
SQ  YFVRLEVRRGDLAALLSGVRQVSEDVRSPAGPKVPWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQVYRQRRKLIAEI
SQ  AFQYRHGDPIPRVEYTAEEIATWKEVYTTLKGLYATHACGEHLEAFALLERFSGYREDNIPQLEDVSRFLKERTGFQLRP
SQ  VAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPDCCHELLGHVPMLADRTFAQFSQDIGLASLGASDEEIEKLSTL
SQ  YWFTVEFGLCKQNGEVKAYGAGLLSSYGELLHCLSEEPEIRAFDPEAAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYAS
SQ  RIQRPFSVKFDPYTLAIDVLDSPQAVRRSLEGVQDELDTLAHALSAIG
//