Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

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

Upstream transcription factor

81647;29452;24817;81646;24705

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

Gene ontology

GO:0043195 (C) terminal button [P97904 ];
GO:0016597 (F) amino acid binding [P97904 ];
GO:0004511 (F) tyrosine 3-monooxygenase activity [P04177, P97904 ];
GO:0005829 (C) cytosol [P97904 ];
GO:0042136 (P) neurotransmitter biosynthetic process [P04177 ];
GO:0035240 (F) dopamine binding [P97904 ];
GO:0008021 (C) synaptic vesicle [P97904 ];
GO:0008198 (F) ferrous iron binding [P97904 ];
GO:0008199 (F) ferric iron binding [P97904 ];
GO:0001666 (P) response to hypoxia [P97904 ];
GO:0005739 (C) mitochondrion [P04177 ];
GO:0006585 (P) dopamine biosynthetic process from tyrosine [P04177, P97904 ];
GO:0051289 (P) protein homotetramerization [P97904 ];
GO:0005506 (F) iron ion binding [P04177 ];
GO:0048545 (P) response to steroid hormone stimulus [P97904 ];
GO:0030659 (C) cytoplasmic vesicle membrane [P04177 ];
GO:0055114 (P) oxidation reduction [P04177 ];

Links

SwissProt

P04177; P97904

Entrez Gene

25085



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  Last Modified: 2009-03-24  
  Design by Zhao Min