Receptor-activated non-selective cation channel involved in pain detection and possibly also in cold perception, oxygen concentration perception, cough, itch, and inner ear function (PubMed:24140646). Shows 8-fold preference for divalent over monovalent cations. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of irritants, such as allylthiocyanate (AITC) found in mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from garlic, and acrolein, an irritant from tears gas and vehicle exhaust fumes (PubMed:16564016). Acts also as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Is activated by a large variety of structurally unrelated electrophilic and non-electrophilic chemical compounds. Electrophilic ligands activate TRPA1 by interacting with critical N-terminal Cys residues in a covalent manner, whereas mechanisms of non-electrophilic ligands are not well determined. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system. A cytosolic factor (probably pyrophosphate, polytriphosphate, polyP4, polyP25, polyP45, and/or polyP65) is necessary for TRPA1 activation by irritants (PubMed:17567811). Such factor acts by keeping TRPA1 in a agonist-sensitive state (PubMed:17567811). Inhibited by the potent blocker of TRPV channels ruthenium red, A-967079 (PubMed:15843607, PubMed:29703838, PubMed:31447178). Activated by icilin, sulfhydryl reactive agent MTSEA, N-methyl maleimide (NMM), and PF-4840154 (PubMed:17237762, PubMed:29703838). Homotetramer (PubMed:21908607). Interacts with TMEM100 (PubMed:25640077). Interacts with EGLN1 (PubMed:21873995). Interacts with the scorpion wasabi receptor toxin at the same site that electrophiles but in a non-covalent manner (By similarity). Expressed in inner ear (at protein level). Specifically expressed in a subset of nociceptive neurons. Expressed in the same neurons that TRPV1. In contrast, it is not expressed in neurons expressing TRPM8. Expressed in the superior cervical ganglion of vagus nerve. Expressed in the inferior ganglion (nodose ganglion) of vagus nerve (PubMed:21873995). Expressed in dorsal root ganglia neurons (PubMed:21873995). During utricle development, it is first expressed at 15 dpc and 16 dpc and peaks at 17 dpc. It drops at 18 dpc but increases again at 19 dpc, possibly corresponding to a second wave of hair cells that are generated at 15 dpc. 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 followed by a crescent-shaped structure that surrounds the protein core. TRPA1 activation by electrophiles occurs though covalent modification of specific cysteine residues in the N-terminal cytoplasmic domain (PubMed:17237762, PubMed:22207754). 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-634 and Cys-859 in hyperoxia may override the hydroxylase EGLN1-mediated inhibition, causing TRPA1 activation. Mice display normal cold sensitivity and unimpaired auditory function, suggesting that this channel is not required for the initial detection of noxious cold or sound. However, they exhibit pronounced deficits in bradykinin-evoked nociceptor excitation and pain hypersensitivity. Belongs to the transient receptor (TC 1.A.4) family. The power behind pain - Issue 82 of May 2007