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FLASH GENE
Symbol TRPA1 contributors: mct - updated : 27-02-2016
HGNC name transient receptor potential cation channel, subfamily A, member 1
HGNC id 497
PROTEIN
PHYSICAL PROPERTIES Hydrophobic
STRUCTURE
motifs/domains
  • a N terminus related to the protein ankyrin (fiveteen ANK repeats)
  • five potential N glycosylation sites
  • a C terminus related to transmembrane proteins (seven hydrophobic regions), and basic residues in the C-terminus are strongly involved in TRPA1 voltage and chemical sensitivity , that is an important regulator of TRP channel activity , and mutations in C-terminal acidic domain affect kinetics of Ca2+-induced potentiation
  • HOMOLOGY
    interspecies homolog to Drosophila CG5751
    homolog to C.elegans Y71A12B.4
    homolog to murine Trpa1
    homolog to rattus Trpa1
    Homologene
    FAMILY
  • transient receptor family
  • TRP cation channel superfamily
  • CATEGORY regulatory , receptor membrane , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
    text type II membrane protein
    basic FUNCTION
  • playing a role in signal transduction and growth control
  • playing a role in the maintenance of the normal phenotype
  • having cation channel activity
  • candidate for the mechanosensitive transduction channel of cochlear ear cells, participating in the perception of sounds
  • is an important component of the transduction machinery through which environmental irritants and endogenous proalgesic agents depolarize nociceptors to elicit inflammatory pain
  • acting as a ionotropic cannabinoid receptor
  • implicated in the mediation of nociceptive and inflammatory signals in response to pungent ingredients, in the development of cold hyperalgesia following inflammation and nerve injury as well as a role in mechanosensation
  • acts as a major sensor for noxious cold
  • acts as a sensor molecule for enterochromaffin cells and may regulate gastrointestinal function
  • is an essential component of the signaling pathways that promote histamine-independent itch
  • TRPV1 and TRPA1, are necessary for development of inflammatory hypersensitivity and are functionally potentiated by growth factors
  • TRPV1 and TRPA1 induced MUC5B release in the nasal airways
  • activation mechanism of TRPA1 may involve N-terminal conformation changes and disulfide bonding between critical cysteine residues
  • activation of meningeal TRPA1 via endogenous or exogenous mechanisms can lead to afferent signaling and headache
  • regulates both itch transduction and pathophysiological changes in the skin that promote chronic itch
  • TRPV1 and TRPA1 in vestibular ganglion (VG) neurons might participate in vestibular function and/or dysfunction such as vertigo
  • function of TRPA1 in cellular function associated to the regulation of agonist-induced Ca(2+) entry by the modulation of STIM1/ORAI1 interaction
  • TRPA1, like TRPV1, mediates F2RL1-triggered pancreatic nociception and that TRPA1 in collaboration with TRPV1 latently contributes to pancreatitis-related pain
  • is essential to the nociceptive effects induced by one of the most important mediators of inflammatory pain, prostaglandin E2 (PGE2)
  • TRPV1, TRPA1, and TRPM8 are important to start up a systemic response of energy expenditure, energy allocation, and water retention
  • considered to be a key player in nociception and inflammatory pain
  • chemo-sensitive cation channel that can be activated by a variety of external and internal stimuli, leading to the influx of Ca2+
  • TRPA1 channels may be determinants of Airway smooth muscle (ASM) contractility and local inflammation control, positioning them as part of novel mechanisms that control (patho)physiological function of airways and ASM
  • BDKRB1 and the transient receptor potential ankyrin 1 (TRPA1) work as initiators and gatekeepers of nociception and inflammation
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS inflammation
    text ion transport (passive transporter); growth control
    PATHWAY
    metabolism
    signaling signal transduction
    response to stimulus
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • functional interaction of PAR2 and TRPA1 in dorsal root ganglion (DRG) neurons could contribute to the sensation of inflammatory pain
  • interaction of TRPV1 and TRPA1 signaling pathways (sensitization of TRPV1 via activation of TRPA1, which involves adenylyl cyclase, increased cAMP, subsequent translocation and activation of PKA, and phosphorylation of TRPV1 at PKA phosphorylation residues)
  • disruption of ZBTB20 in nociceptors led to a marked decrease in the expression levels of TRPV1, TRPA1 and TRPM8
  • TMEM100 selectively potentiates TRPA1 activity in a TRPV1-dependent manner
  • cell & other
    REGULATION
    activated by low temperatures
    allyl isothiocyanate and tetrahydrocannabinol (THC)
    bradykinin
    wasabi or garlic (activation that may stimulate cholecystokinin secretion from the intestine and thus improve the digestive functions)
    Other critically regulated by Ca2+ ions, and this mechanism represents a self-modulating feedback loop that first augments and then inhibits the initial activation
    ASSOCIATED DISORDERS
    corresponding disease(s) FEPS1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in mesenchymal tumor
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    represents a promising target for the prevention or treatment of cold-induced pain
    miscelleaneouspain 
    promising novel drug target for the treatment of chronic pain and hypersensitivity
    neurosensorial  
    future TRPA1 modulating drugs may modify the perception of odorants
    respiratory  
    TRPM8 and TRPA1 agonists may be promising new therapies for asthma
    ANIMAL & CELL MODELS
  • TRPA1-deficient mice displayed little to no scratching in response to the pruritogens