TRPA1

The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control. [provided by RefSeq]

transient receptor potential cation channel, subfamily A, member 1

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:21873995, PubMed:23199233, PubMed:25389312, PubMed:25855297).
Shows 8-fold preference for divalent over monovalent cations (PubMed:31447178).
Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of irritants, such as allylthiocyanate (AITC) from mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from garlic, and acrolein, an irritant from tears gas and vehicle exhaust fumes (PubMed:25389312, PubMed:27241698, PubMed:30878828, PubMed:20547126).
Acts also as an ionotropic cannabinoid receptor by being activated by delta9-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312).
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 (By similarity).

Biological Process calcium ion transmembrane transport Source:UniProtKB2 Publications
Biological Process cell surface receptor signaling pathway Source:Ensembl
Biological Process cellular calcium ion homeostasis Source:MGI1 Publication
Biological Process cellular response to hydrogen peroxide Source:MGI1 Publication
Biological Process cellular response to organic substance Source:Ensembl
Biological Process detection of chemical stimulus involved in sensory perception of pain Source:Ensembl
Biological Process detection of mechanical stimulus involved in sensory perception of pain Source:Ensembl
Biological Process ion transport Source:ProtInc1 Publication
Biological Process protein homotetramerization Source:UniProtKB1 Publication
Biological Process response to cold Source:Ensembl
Biological Process response to organic cyclic compound Source:Ensembl
Biological Process response to organic substance Source:UniProtKB1 Publication
Biological Process response to pain Source:Ensembl
Biological Process response to xenobiotic stimulus Source:Ensembl
Biological Process sensory perception of pain Source:UniProtKB1 Publication
Biological Process thermoception Source:Ensembl

Cell membrane

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.

Cytoplasmic: 1-719
Helical: 720-740
Extracellular: 741-764
Helical: 765-785
Cytoplasmic: 786-803
Helical: 804-824
Extracellular: 825-829
Helical: 830-850
Cytoplasmic: 851-873
Helical: 874-894
Extracellular: 895-901
Helical: 902-922
Cytoplasmic: 923-934
Helical: 935-956
Extracellular: 957-1119

TRPA1 activation by electrophiles occurs though covalent modification of specific cysteine residues in the N-terminal cytoplasmic domain (PubMed:25389312).
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.