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Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases |
Basic Information |
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Enzyme Number | 1.14.16.2 |
Official Name | tyrosine 3-monooxygenase |
Name from literature | tyrosine hydroxylase |
Pathway from literature | the catecholamine biosynthetic pathway |
Pathway from KEGG |
Human Diseases; Neurodegenerative Diseases; Parkinson's disease; map05020 |
Amino Acid Metabolism; Tyrosine metabolism; map00350 | |
Organisms | Rat (10116) |
Genome localization | 1q41[25085 ], |
Comments | The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC 2.7.11.27, [acetyl-CoA carboxylase] kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin. |
Rate-limiting Description | "We have employed buoyant density fractionation to separate the dopaminergic neurons of the two compartments and compare their subsequent phenotype development with respect to their expression of the gene encoding tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine biosynthetic pathway." (10476677) |
Regulatory Information |
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Upstream transcription factor | |
Regulatory type | Detail |
phosphorylation; | P04177 |
phosphorylation; | P04177:from_uniprot:19_Phosphoserine; by CaMK2 |
phosphorylation; | P04177:from_uniprot:31_Phosphoserine |
phosphorylation; | P04177:from_uniprot:40_Phosphoserine; by PKA |
transcriptional factor;Atranscriptional factor-2(81647) | "transcriptional regulation by Atranscriptional factor-2" (12196528) |
transcriptional factor;"HIF1alpha(24817),HIF2alpha(29452)" | "Tyrosine hydroxylase promoter activity is regulated by the von Hippel-Lindau tumor suppressor protein and HIF1alpha and HIF2alpha in PC12 cells" (12675925) |
transcriptional factor; | "TH is transcriptionally regulated by estradiol in opposite directions depending on ER subtype. The overlapping ERE and CRE/CaRE may integrate interactions elicited by various regulators of TH transcription including cAMP and estrogens." (15935066) |
transcriptional factor;"Atranscriptional factor-2(81647),CREB(81646)" | "both Atranscriptional factor-2 and CREB mediate activation of tyrosine hydroxylase gene transcription by nicotine" (16452470) |
phosphorylation; | "Intermittent hypoxia-induced phosphorylation of TH facilitates removal of endogenous inhibition of TH, leading to increased synthesis of dopamine." (12692140) |
phosphorylation; | "data suggest that cyclin-dependent kinase 5 (cdk5) phosphorylation of tyrosine hydroxylase(TH) is an important regulator of TH activity through stabilization of TH protein levels" (15471880) |
phosphorylation; | "Urocotin 2 induces noradrenaline secretion and TH phosphorylation through the Protein Kinase A (PKA) pathway and the PKA-Mitogen-Activated Protein Kinase 1/2 pathway, respectively" (15809070) |
phosphorylation; | "The kinetics of reduction of ferric TyrH by several reductants were determined by anaerobic stopped-flow spectroscopy. phosphorylation does not directly regulate the interconversion of the ferric and ferrous forms" (16475826) |
phosphorylation; | "Neither PKA nor ERK2 phosphorylation of tyrosine hydroxylase is affected by pre-existing negative charge at regulatory serines. S40 phosphorylation by PKA is regulated by bound dopamine, but ERK2 action on S31 is unaffected." (16503426) |
phosphorylation; | "Results suggest that morphine withdrawal increases noradrenaline turnover in the PVN, at least in part, via ERK(1/2)-dependent phosphorylation of TH at Ser31." (17823252) |
phosphorylation; | "Our results suggest that subthalamic stimulation may increase tyrosine hydroxylase activity via increased phosphorylation." (18185104) |
transcriptional factor;retinoic acid receptor(24705) | "In this study, we investigated whether the retinoic acid receptor (RAR), a transcription factor specifically activated by all-trans-RA, could directly regulate transcription of tyrosine hydroxylase (TH), the first and rate-limiting step in the catecholamine biosynthesis pathway." (16805833) |
Gene ontology |
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Gene ontology |
GO:0043195 (C) terminal button [P97904 ]; |
Links |
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SwissProt | |
Entrez Gene |
Copyright 2009, Center for Bioinformatics | |||
Last Modified: 2009-03-24 | |||
Design by Zhao Min |