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

Basic Information

Enzyme Number

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


Human (9606)

Genome localization

11p15.5[7054 ],


The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC, [acetyl-CoA carboxylase] kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.

Rate-limiting Description

"The TH (tyrosine hydroxylase) gene encodes the rate-limiting enzyme of catecholamine biosynthesis, and is involved in the pathogenesis of hypertension, but the relationship of its variants with hypertension has not been extensively studied." (18208403)

Regulatory Information

Upstream transcription factor


Regulatory type



"Phosphorylation of human recombinant tyrosine hydroxylase isoforms 1 and 2: an additional phosphorylated residue in isoform 2, generated through alternative splicing." (1680128#11359875#7901013#11359875#7901013)

signal pathway;"ERK,calcium-mediated events"

"hierarchical phosphorylation provides a mechanism whereby the two major human TH isoforms (1 and 2) can be differentially regulated with only isoform 1 responding to the ERK pathway, whereas isoform 2 is more sensitive to calcium-mediated events" (16644734)

transcriptional factor;DJ-1(11315)

"DJ-1 transcriptionally up-regulates the human tyrosine hydroxylase by inhibiting the sumoylation of pyrimidine tract-binding protein-associated splicing factor" (16731528)

transcriptional factor;NRSF(5978)/REST(5978)

"NRSF/REST functions as a repressor of TH transcription in NSCs via a mechanism dependent on the TH NRSE/RE1 sites." (16764822)








P07101:from_uniprot:71_Phosphoserine; by PKA

transcriptional factor;"ATF-2(1386),CREB(1385)"

"Identification of ATF-2 as a transcriptional regulator for the tyrosine hydroxylase gene.First, by using reporter constructs, we found that the transcription mediated by cAMP-responsive element (CRE) was selectively enhanced in the V-1 cells, and TH promoter activity was totally dependent on the CRE in the promoter region of the TH gene" (12196528)

transcriptional factor;YWHAZ(7534)

"Interaction of phosphorylated tyrosine hydroxylase with 14-3-3 proteins: evidence for a phosphoserine 40-dependent association." (11359875)

Gene ontology

Gene ontology

GO:0009072 (P) aromatic amino acid family metabolic process [Q16846, Q15587, O43816 ];
GO:0004511 (F) tyrosine 3-monooxygenase activity [Q16846, P07101, Q15587, O43816 ];
GO:0043473 (P) pigmentation [P07101 ];
GO:0042136 (P) neurotransmitter biosynthetic process [P07101 ];
GO:0043005 (C) neuron projection [P07101 ];
GO:0005790 (C) smooth endoplasmic reticulum [P07101 ];
GO:0003007 (P) heart morphogenesis [P07101 ];
GO:0043204 (C) perikaryon [P07101 ];
GO:0007613 (P) memory [P07101 ];
GO:0005515 (F) protein binding [P07101 ];
GO:0042462 (P) eye photoreceptor cell development [P07101 ];
GO:0001666 (P) response to hypoxia [P07101 ];
GO:0007601 (P) visual perception [P07101 ];
GO:0006585 (P) dopamine biosynthetic process from tyrosine [P07101 ];
GO:0045471 (P) response to ethanol [P07101 ];
GO:0033162 (C) melanosome membrane [P07101 ];
GO:0042421 (P) norepinephrine biosynthetic process [P07101 ];
GO:0005506 (F) iron ion binding [Q16846, P07101, Q15587, O43816 ];
GO:0009898 (C) internal side of plasma membrane [P07101 ];
GO:0007626 (P) locomotory behavior [P07101 ];
GO:0001963 (P) synaptic transmission, dopaminergic [P07101 ];
GO:0007612 (P) learning [P07101 ];
GO:0048596 (P) embryonic camera-type eye morphogenesis [P07101 ];
GO:0005634 (C) nucleus [P07101 ];
GO:0008016 (P) regulation of heart contraction [P07101 ];
GO:0042418 (P) epinephrine biosynthetic process [P07101 ];
GO:0055114 (P) oxidation reduction [Q16846, P07101, Q15587, O43816 ];

Tissue expression

Tissue From HPRD

Nervous system [01865 ];

Tissue specificity

Mainly expressed in the brain and adrenal glands [P07101 ];

Disease relevance


Defects in TH are the cause of autosomal recessive Segawa syndrome [MIM:605407];
also known as DOPA-responsive dystonia. Typically, it begins in childhood or adolescence with progressive difficulty in walking and, in some cases, spasticity. Some cases present with parkinsonian symptoms in infancy and are referred to as autosomal recessive infantile parkinsonism [P07101 ];



O43816; P07101; Q15587; Q16846

Entrez Gene




  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min