TRPA1
entrez
8989
canonical
uniprot
O75762
canonical
ensembl
ENSG00000104321
resolver
ensp
ENSP00000262209
resolver
ensp
ENSP00000529869
resolver
enst
ENST00000262209
resolver
enst
ENST00000859810
resolver
genesymbol
TRPA1
resolver
genesymbol_syn
ANKTM1
resolver
hgnc
HGNC:497
resolver
uniprot
A6NIN6
resolver
uniprot_entry
TRPA1_HUMAN
resolver
uniprot_sec
A6NIN6
resolver
activity_regulation
ACTIVITY REGULATION: Electrophilic ligands activate the channel by covalent modification of intracellular cysteines; Cys-621 plays a key role in covalent binding of electrophiles (PubMed:25389312, PubMed:27241698, PubMed:31866091, PubMed:32641835). Extracellular Ca(2+) both potentiates and inactivates TRPA1; a rapid potentiation follows by slow desensitization (By similarity). Activated by increase in intracellular Ca(2+) concentration (PubMed:17259981). Inhibited by the potent blocker of TRPV channels ruthenium red, A-967079, AP-18, HC-030031, and aryl sulfonamide derivative (S)-N-(4-chlorobenzyl)-1-((4-fluorophenyl)sulfonyl)pyrrolidine-2-carboxamide (ASD) (PubMed:17567811, PubMed:20547126, PubMed:21402443, PubMed:21873995, PubMed:30878828). Activated by benzyl isothiocyanate (BITC), iodoacetamide, sulfhydryl reactive agent MTSEA, N-methyl maleimide (NMM), N-ethylmaleimide (NEM), and 2-aminoethyldiphenylborinate (2-APB) (PubMed:17164327, PubMed:17567811, PubMed:21873995, PubMed:25855297, PubMed:27241698). Also activated by hyperoxia (PubMed:21873995). Activated by intracellular Zn(2+) (PubMed:19202543). TRPA1 activation may critically depend on the presence of small intracellular compounds such as polyphosphates (PubMed:17567811). {ECO:0000250|UniProtKB:Q6RI86, ECO:0000269|PubMed:17164327, ECO:0000269|PubMed:17259981, ECO:0000269|PubMed:17567811, ECO:0000269|PubMed:19202543, ECO:0000269|PubMed:20547126, ECO:0000269|PubMed:21402443, ECO:0000269|PubMed:21873995, ECO:0000269|PubMed:25389312, ECO:0000269|PubMed:25855297, ECO:0000269|PubMed:27241698, ECO:0000269|PubMed:30878828, ECO:0000269|PubMed:31447178, ECO:0000269|PubMed:31866091, ECO:0000269|PubMed:32641835}.
uniprot
proteins
amino_acid_sequence
MKRSLRKMWRPGEKKEPQGVVYEDVPDDTEDFKESLKVVFEGSAYGLQNFNKQKKLKRCDDMDTFFLHYAAAEGQIELMEKITRDSSLEVLHEMDDYGNTPLHCAVEKNQIESVKFLLSRGANPNLRNFNMMAPLHIAVQGMNNEVMKVLLEHRTIDVNLEGENGNTAVIIACTTNNSEALQILLKKGAKPCKSNKWGCFPIHQAAFSGSKECMEIILRFGEEHGYSRQLHINFMNNGKATPLHLAVQNGDLEMIKMCLDNGAQIDPVEKGRCTAIHFAATQGATEIVKLMISSYSGSVDIVNTTDGCHETMLHRASLFDHHELADYLISVGADINKIDSEGRSPLILATASASWNIVNLLLSKGAQVDIKDNFGRNFLHLTVQQPYGLKNLRPEFMQMQQIKELVMDEDNDGCTPLHYACRQGGPGSVNNLLGFNVSIHSKSKDKKSPLHFAASYGRINTCQRLLQDISDTRLLNEGDLHGMTPLHLAAKNGHDKVVQLLLKKGALFLSDHNGWTALHHASMGGYTQTMKVILDTNLKCTDRLDEDGNTALHFAAREGHAKAVALLLSHNADIVLNKQQASFLHLALHNKRKEVVLTIIRSKRWDECLKIFSHNSPGNKCPITEMIEYLPECMKVLLDFCMLHSTEDKSCRDYYIEYNFKYLQCPLEFTKKTPTQDVIYEPLTALNAMVQNNRIELLNHPVCKEYLLMKWLAYGFRAHMMNLGSYCLGLIPMTILVVNIKPGMAFNSTGIINETSDHSEILDTTNSYLIKTCMILVFLSSIFGYCKEAGQIFQQKRNYFMDISNVLEWIIYTTGIIFVLPLFVEIPAHLQWQCGAIAVYFYWMNFLLYLQRFENCGIFIVMLEVILKTLLRSTVVFIFLLLAFGLSFYILLNLQDPFSSPLLSIIQTFSMMLGDINYRESFLEPYLRNELAHPVLSFAQLVSFTIFVPIVLMNLLIGLAVGDIAEVQKHASLKRIAMQVELHTSLEKKLPLWFLRKVDQKSTIVYPNKPRSGGMLFHIFCFLFCTGEIRQEIPNADKSLEMEILKQKYRLKDLTFLLEKQHELIKLIIQKMEIISETEDDDSHCSFQDRFKKEQMEQRNSRWNTVLRAVKAKTHHLEP
uniprot
proteins
disease_involvement
DISEASE: Episodic pain syndrome, familial, 1 (FEPS1) [MIM:615040]: 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. {ECO:0000269|PubMed:20547126}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q8BLA8, ECO:0000269|PubMed:17164327, ECO:0000269|PubMed:17259981, ECO:0000269|PubMed:19202543, ECO:0000269|PubMed:20547126, ECO:0000269|PubMed:21195050, ECO:0000269|PubMed:21873995, ECO:0000269|PubMed:23199233, ECO:0000269|PubMed:25389312, ECO:0000269|PubMed:27241698, ECO:0000269|PubMed:30878828, ECO:0000269|PubMed:31866091, ECO:0000269|PubMed:32641835, ECO:0000269|PubMed:33152265}.
uniprot
proteins
mass_dalton
127501
uniprot
proteins
mutagenesis
MUTAGEN 173; /note="C->S: Decrease in activation by hyperoxia and diallyl disulfide."; /evidence="ECO:0000269|PubMed:21873995"; MUTAGEN 192; /note="C->S: Decrease in activation by hyperoxia and diallyl disulfide."; /evidence="ECO:0000269|PubMed:21873995"; MUTAGEN 394; /note="P->A: Loss of answer to hypoxia and hydroxylase inhibitor DMOG, but not to AITC and hyperoxia."; /evidence="ECO:0000269|PubMed:21873995"; MUTAGEN 620; /note="K->A: Important decrease in electrophile-evoked response."; /evidence="ECO:0000269|PubMed:27241698"; MUTAGEN 621; /note="C->A,S: Do not exhibit detectable current upon electrophile stimulation. No change in answer to hyperoxia and diallyl disulfide. Do not exhibit detectable currents upon stimulation with agonist JT010."; /evidence="ECO:0000269|PubMed:21873995, ECO:0000269|PubMed:27241698, ECO:0000269|PubMed:30878828, ECO:0000269|PubMed:31866091, ECO:0000269|PubMed:32641835"; MUTAGEN 622; /note="P->A: Loss of activation by the scorpion wasabi receptor toxin."; /evidence="ECO:0000269|PubMed:31447178"; MUTAGEN 633; /note="C->S: Decrease in activation by hyperoxia and diallyl disulfide. Important decrease in activation by hyperoxia and diallyl disulfide; when associated with S-856."; /evidence="ECO:0000269|PubMed:21873995"; MUTAGEN 634; /note="M->L: Loss of activation by the scorpion wasabi receptor toxin."; /evidence="ECO:0000269|PubMed:31447178"; MUTAGEN 641; /note="C->A,S: Decrease in electrophile-evoked and hyperoxia response."; /evidence="ECO:0000269|PubMed:21873995"; MUTAGEN 641; /note="C->S: Does not affect activation by electrophiles."; /evidence="ECO:0000269|PubMed:32641835"; MUTAGEN 646; /note="T->P: Loss of activation by the scorpion wasabi receptor toxin."; /evidence="ECO:0000269|PubMed:31447178"; MUTAGEN 665; /note="C->A,L,S: Decrease in electrophile-evoked and hyperoxia response. Does not affect covalent agonist BITC electrophile-evoked."; /evidence="ECO:0000269|PubMed:21873995, ECO:0000269|PubMed:27241698, ECO:0000269|PubMed:31866091, ECO:0000269|PubMed:32641835"; MUTAGEN 788; /note="E->S: Lacks calcium-mediated potentiation but retains calcium-mediated desensitization. Lacks calcium-mediated potentiation and lacks calcium-mediated desensitization; when associated with S-191 and S-805."; /evidence="ECO:0000269|PubMed:32641835"; MUTAGEN 791; /note="Q->S: Lacks calcium-mediated potentiation and lacks desensitization; when associated with S-788 and S-805."; /evidence="ECO:0000269|PubMed:32641835"; MUTAGEN 805; /note="N->S: Lacks calcium-mediated potentiation and lacks desensitization; when associated with S-788 and S-791."; /evidence="ECO:0000269|PubMed:32641835"; MUTAGEN 856; /note="C->S: Decrease in activation by hyperoxia and diallyl disulfide. Important decrease in activation by hyperoxia and diallyl disulfide; when associated with S-633."; /evidence="ECO:0000269|PubMed:21873995"; MUTAGEN 909; /note="F->A,T: Loss of inhibition by A-967079, AP-18, and ASD. Increase in activation by cinnamaldehyde, AITC and acrolein."; /evidence="ECO:0000269|PubMed:25855297, ECO:0000269|PubMed:30878828"; MUTAGEN 915; /note="D->A: Abolishes zinc influx. Abolishes activation by extracellular but not by intracellular zinc."; /evidence="ECO:0000269|PubMed:19202543"; MUTAGEN 944; /note="F->A: Loss of inhibition by A-967079, AP-18, and ASD. Weak or no change in activation by cinnamaldehyde, AITC and acrolein."; /evidence="ECO:0000269|PubMed:30878828
uniprot
proteins
post_translational_modification
PTM: TRPA1 activation by electrophiles occurs though covalent modification of specific cysteine residues in the N-terminal cytoplasmic domain. {ECO:0000269|PubMed:32641835, ECO:0000305|PubMed:25389312}.; PTM: 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. {ECO:0000269|PubMed:21873995}.; PTM: Oxidation of Cys-633 and Cys-856 in hyperoxia may override the hydroxylase EGLN1-mediated inhibition, causing TRPA1 activation. {ECO:0000269|PubMed:21873995}.
uniprot
proteins
protein_family
Transient receptor (TC 1.A.4) family
uniprot
proteins
pubmed
10066796
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
17164327
uniprot
proteins
pubmed
17259981
uniprot
proteins
pubmed
17567811
uniprot
proteins
pubmed
19202543
uniprot
proteins
pubmed
20547126
uniprot
proteins
pubmed
21195050
uniprot
proteins
pubmed
21402443
uniprot
proteins
pubmed
21873995
uniprot
proteins
pubmed
23199233
uniprot
proteins
pubmed
25389312
uniprot
proteins
pubmed
25855297
uniprot
proteins
pubmed
26200340
uniprot
proteins
pubmed
27241698
uniprot
proteins
pubmed
30878828
uniprot
proteins
pubmed
31447178
uniprot
proteins
pubmed
31866091
uniprot
proteins
pubmed
32641835
uniprot
proteins
pubmed
33152265
uniprot
proteins
sequence_length
1119
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20547126, ECO:0000269|PubMed:21873995, ECO:0000269|PubMed:25389312, ECO:0000269|PubMed:25855297}; Multi-pass membrane protein {ECO:0000269|PubMed:31866091}.
uniprot
proteins
transmembrane_region
TRANSMEM 719..739; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:31866091, ECO:0007744|PDB:6PQO"; TRANSMEM 768..793; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:31866091, ECO:0007744|PDB:6PQO"; TRANSMEM 799..823; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:31866091, ECO:0007744|PDB:6PQO"; TRANSMEM 830..850; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:31866091, ECO:0007744|PDB:6PQO"; TRANSMEM 863..892; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:31866091, ECO:0007744|PDB:6PQO"; TRANSMEM 934..960; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:31866091, ECO:0007744|PDB:6PQO
uniprot
proteins