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FLASH GENE
Symbol TH contributors: mct/npt - updated : 20-04-2020
HGNC name tyrosine hydroxylase
HGNC id 11782
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal sequence (residues 1-43), which corresponds to an extension to the TH regulatory domain, interacts with negatively charged membranes, is a conformationally versatile motif, and binds 14-3-3 proteins and membranes ; phosphorylation of the N-terminal portion of TH regulates the degradation of this enzyme by the ubiquitin-proteasome pathway
    • mono polymer tetramer
    HOMOLOGY
    interspecies homolog to murine Th
    Homologene
    FAMILY
  • biopterin-dependent aromatic amino acid hydroxylase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus
    basic FUNCTION
  • tyrosine 3-monooxygenase
  • potentially associated with longevity in the male
  • catalyzes the rate limiting step in the biosynthesis of catecholamines in the central and peripheral nervous system
  • the promoter is able to direct GFP expression to TH+ neurons of substantia nigra
  • POU3F4 and TH synergistically promote the differentiation of neural stem cells into dopaminergic neurons
  • rate-limiting enzyme in catecholamine biosynthesis, and the regulation of its transcription is critical for the specification and maintenance of catecholaminergic neuron phenotypes
  • could represent a pathomechanism whereby obesity contributes to periodontitis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    catecholamines
    a component
  • is a tetramer composed of regulatory, catalytic and tetramerization domains
    • INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • ferrous ion
    • protein
  • up-regulating retinal genes (OPN1MW, OPN1LW, TIMP3, RP1L1, GNGT2, CRX, ARR3, GUCA1A, IMPDH1, and PDE6C) (Liu 2007)
  • down-regulating retinal genes GNGT1 and GNB3 (Liu 2007)
  • role for MTA1 as an upstream coactivator of TH
  • during dopaminergic (DA) neurogenesis, NR4A2 directly targets human tyrosine hydroxylase (TH)
  • NR4A2 represses TH expression via SIRT1 in human neural stem cells
  • SLC6A3 expression affects TH expression and phosphorylation largely in Dopamine (DA) terminal field compartments
  • CTCF is a novel regulator of TH transcription in the forebrain
  • TH induced mitochondrial biogenesis, fission, and mitophagy in an ESRRA-dependent manner
  • NR4A2 is an orphan transcription factor that influences the expression of several key proteins of dopaminergic (DA) neurons, including tyrosine hydroxylase (TH), dopamine transporter (SLC6A3), and vesicular monoamine transporter (SLC18A1)
    • cell & other
    REGULATION
    Other catalytic activity increased by phosphorylation
    TH is highly regulated, notably by phosphorylation of several Ser/Thr residues in the N-terminal tail, and Ser-31 phosphorylation may regulate TH subcellular localization by enabling its transport along microtubules, notably toward the projection terminals
    expression of TH is epigenetically regulated in neural stem cells
    ASSOCIATED DISORDERS
    corresponding disease(s) DPDV
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in schizophrenia, bipolar disorder and alcoholism
    constitutional     --over  
    obesity-associated stimuli induce a TH upregulation in periodontal cells and tissues
    tumoral germinal mutation      
    in familial isolated pituitary adenoma
    Susceptibility
  • to alterations in autonomic activity and blood pressure
    • Variant & Polymorphism SNP
  • common genetic variants in the proximal TH promoter, especially at C-824T and A-581G, are associated to alterations in autonomic activity and blood pressure
    • Candidate gene
    Marker
  • tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma is a marker of worse outcome
  • in high-risk metastatic Neuroblastoma, TH and DCX mRNA quantification could be used for the assessment of response to treatment and for early detection of progressive disease or relapses
    • Therapy target
    ANIMAL & CELL MODELS