TRPA1/TSA

Expressed in embryos at 12 weeks of age.

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.

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). Acts also 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).

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.

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.

Belongs to the transient receptor (TC 1.A.4) family.

• Cell membrane
• Multi-pass membrane protein

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

• entrezGene:8989
• omim:604775
• swissprot:O75762

Proteins

Neuroscience

127501Da