TRPA1
GeneName
TRPA1
Summary
TRPA1, also known as TSA, INS, or p120, is a 128 kDa transmembrane protein primarily expressed in sensory neurons and various tissues, including the respiratory and gastrointestinal tracts. It functions as a calcium-permeable cation channel that is activated by environmental stimuli such as temperature changes, mechanical stress, and chemical irritants. TRPA1 plays a crucial role in nociception, the detection of pain, and is involved in various cellular responses, including the regulation of insulin secretion and blood circulation. It is localised to the plasma membrane, axon, and apical plasma membrane, and is known for its involvement in the cellular response to a range of stimuli, including cold, heat, and toxic substances.
Importance
TRPA1 is relevant to: - Pain pathways and the sensory perception of pain, making it a target for analgesic drug development - Regulation of insulin secretion, which has implications for diabetes research - Responses to environmental stressors, including temperature and chemical irritants, highlighting its role in sensory biology - Potential therapeutic target in conditions related to inflammation and neurogenic pain due to its activation by inflammatory mediators and irritants
Top Products
For researchers investigating TRPA1, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-TRPA1/TSA antibody (ab62053), which has garnered 14 citations and is particularly effective for immunohistochemistry (IHC). This product is trusted for its performance in the field. Additionally, we offer the recombinant antibody, Anti-TRPA1/TSA antibody [EPR26211-139] (ab320715), which is suitable for both Western blotting (WB) and IHC applications. This recombinant option provides the added benefit of batch-to-batch consistency, making it a reliable choice for your TRPA1 research needs.
Abcam Product Citation Summary
The data indicates that the TRPA1 target has been studied in the context of mouse dorsal root ganglion neurons, highlighting its relevance in sensory neuron research. The use of immunofluorescence and IHC-IF suggests a focus on visualising TRPA1 expression in these specific neuronal tissues.
Abcam Product Citation Table
Developmental stage
Expressed in embryos at 12 weeks of age.
Domain
C-terminal helices from the four subunits associate to form atypical coiled coil structure; this region is probably involved in binding the inositol polyphosphates that are required for optimal channel activity (in vitro).
The ANK repeat domain consists of a convex stem structure formed by five ANK repeats and 11 additional ANK repeats that form a crescent-shaped structure that surrounds the protein core.
Function
Ligand-activated Ca(2+)-permeable, nonselective cation channel involved in pain detection and possibly also in cold perception, oxygen concentration perception, cough, itch, and inner ear function (PubMed:17259981, PubMed:21195050, PubMed:21873995, PubMed:23199233, PubMed:25389312, PubMed:33152265). Has a relatively high Ca(2+) selectivity, with a preference for divalent over monovalent cations (Ca(2+) > Ba(2+) > Mg(2+) > NH4(+) > Li(+) > K(+)), the influx of cation into the cytoplasm leads to membrane depolarization (PubMed:19202543, PubMed:21195050). Has a central role in the pain response to endogenous inflammatory mediators, such as bradykinin and to a diverse array of irritants. Activated by a large variety of structurally unrelated electrophilic and non-electrophilic chemical compounds, such as allylthiocyanate (AITC) from mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from garlic, and acrolein, an environmental irritant (PubMed:20547126, PubMed:25389312, PubMed:27241698, PubMed:30878828). Electrophilic ligands activate TRPA1 by interacting with critical N-terminal Cys residues in a covalent manner (PubMed:17164327, PubMed:27241698, PubMed:31866091, PubMed:32641835). Non-electrophile agonists bind at distinct sites in the transmembrane domain to promote channel activation (PubMed:33152265). Also acts as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds (By similarity).
Involvement in disease
Episodic pain syndrome, familial, 1
FEPS1
An autosomal dominant neurologic disorder characterized by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold, and physical stress. The period of intense pain is accompanied by breathing difficulties, tachycardia, sweating, generalized pallor, peribuccal cyanosis, and stiffness of the abdominal wall. Affected individuals do not manifest altered pain sensitivity outside the episodes.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
TRPA1 activation by electrophiles occurs though covalent modification of specific cysteine residues in the N-terminal cytoplasmic domain.
Hydroxylation is required for TRPA1 activity inhibition in normoxia. In hypoxia, the decrease in oxygen concentration diminishes the activity of the hydroxylase EGLN1, thus relieving TRPA1 from inhibition and ultimately leading to channel activation.
Oxidation of Cys-633 and Cys-856 in hyperoxia may override the hydroxylase EGLN1-mediated inhibition, causing TRPA1 activation.
Sequence Similarities
Belongs to the transient receptor (TC 1.A.4) family.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
ANKTM1, TRPA1, Transient receptor potential cation channel subfamily A member 1, Ankyrin-like with transmembrane domains protein 1, Transformation-sensitive protein p120, Wasabi receptor, p120