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Gene and Protein Information | |||||||
Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 6 | 0 | 1119 | 8q21.11 | TRPA1 | transient receptor potential cation channel subfamily A member 1 | 61 |
Mouse | 6 | 0 | 1125 | 1 A3 | Trpa1 | transient receptor potential cation channel, subfamily A, member 1 | 129 |
Rat | 6 | 0 | 1125 | 5q11 | Trpa1 | transient receptor potential cation channel, subfamily A, member 1 | 62 |
Previous and Unofficial Names |
ANKTM1 | TRPN1 | ankyrin-like with transmembrane domains 1 | transient receptor potential cation channel |
Database Links | |
Alphafold | O75762 (Hs), Q8BLA8 (Mm), Q6RI86 (Rn) |
CATH/Gene3D | 1.25.40.20 |
ChEMBL Target | CHEMBL6007 (Hs), CHEMBL1075310 (Mm), CHEMBL5160 (Rn) |
DrugBank Target | O75762 (Hs) |
Ensembl Gene | ENSG00000104321 (Hs), ENSMUSG00000032769 (Mm), ENSRNOG00000007354 (Rn) |
Entrez Gene | 8989 (Hs), 277328 (Mm), 312896 (Rn) |
Human Protein Atlas | ENSG00000104321 (Hs) |
KEGG Gene | hsa:8989 (Hs), mmu:277328 (Mm), rno:312896 (Rn) |
OMIM | 604775 (Hs) |
Pharos | O75762 (Hs) |
RefSeq Nucleotide | NM_007332 (Hs), NM_177781 (Mm), NM_207608 (Rn) |
RefSeq Protein | NP_015628 (Hs), NP_808449 (Mm), NP_997491 (Rn) |
UniProtKB | O75762 (Hs), Q8BLA8 (Mm), Q6RI86 (Rn) |
Wikipedia | TRPA1 (Hs) |
Functional Characteristics | |
γ = 87–100 pS; conducts mono- and di-valent cations non-selectively (PCa/PNa = 0.84); outward rectification; activated by elevated intracellular Ca2+ |
Ion Selectivity and Conductance | ||||||
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Ion Selectivity and Conductance Comments | ||||||
TRPA1 exhibits conductance of 98pS in physiological solution, dependent on Ca2+ and Mg2+ concentration [96]. |
Voltage Dependence Comments |
Voltage-dependence not yet described, inactivation by extracellular Ca2+ might be voltage dependent [96]. |
Chemical activators (Human) |
Isothiocyanates (covalent) and 1,4-dihydropyridines (non-covalent) |
Oxidative stress compounds (Mouse) |
4-oxo-nonenal: pEC50 5.7, H2O2 : pEC50 3.6, hypochlorite: EC50 11 ppm (human) and 7 ppm (mouse) [3,20,121] |
Physical activators (Human) |
Cooling (<17°C) (disputed) [62,96,144] |
Download all structure-activity data for this target as a CSV file
Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific activator tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Activator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
TRPA1 is activated by covalent modification of intracellular cysteines [57], activated by bradykinin [9,14,62], probably activated by noxious cold [9,129], but this is disputed [62,96], mechano-activation is still under discussion. TRPA1 is modulated by intra- and extracellular Ca2+ [96]. Snake and fly TRPA1 are a heat-activated channels [50,105,146]. In a calcium imaging study the PGD2 metabolite 15-deoxy-Δ12,14-prostaglandin J2 activated the human TRPA1 expressed in HEK293 cells and in a subset of chemosensitive mouse trigeminal neurons, where this activation was blocked by both the nonselective TRP channel blocker ruthenium red, and the TRPA1 inhibitor HC-030031. Δ12-PGJ2 and 8-iso-PGA2 are also activators of TRPA1 [138]. Further compounds which are reported to activate TRPA1 in vitro include: 2-pentenal (mouse) [14], clotrimazole (human and mouse) [92], WIN55212-2 (mouse) [1] and AM1241 (mouse) [1], sodium hypochlorite (NaOCl; mouse and human) [20], 5,6-EET (mouse) [126], hepoxilin A3 (mouse, rat) [52], 12S-HPETE (mouse, rat) [52], carbon dioxide (rat, mouse) [148], acetic, propinoic, formic, and lactic acids (human, rat, mouse) [147]. |
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Gating inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific gating inhibitor tables |
Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Channel Blockers | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Channel Blocker Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Blocking effects are modulated by divalent cations [96]. |
Immunopharmacology Comments |
Several lines of evidence implicate TRPA1 in inflammation, inflammatory pain and inflammatory diseases [74,82,91,112,130,154]. |
Cell Type Associations | ||||||
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Tissue Distribution | ||||||||
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Tissue Distribution Comments | ||||||||
Note that expression is upregulated by de-ubiquitination by the tumor suppressor (ubiquitin hydrolase) CYLD. |
Functional Assays | ||||||||||
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Physiological Functions | ||||||||
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Physiological Consequences of Altering Gene Expression | ||||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||||||||||||||||||
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Gene Expression and Pathophysiology | ||||||||||||
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Biologically Significant Variant Comments |
A single nucleotide polymorphism (SNP), which results in the Glu179Lys substitution, has been found in pain patients who experience paradoxical heat sensation [21]. TRPA1 SNPs are associated with preference for mentholated cigarettes in heavy smokers [143]. |
General Comments |
Note that Drs Liu and Fan contributed equally to the September 2013 update of this page. |
1. Akopian AN, Ruparel NB, Patwardhan A, Hargreaves KM. (2008) Cannabinoids desensitize capsaicin and mustard oil responses in sensory neurons via TRPA1 activation. J Neurosci, 28 (5): 1064-75. [PMID:18234885]
2. Andersson DA, Gentry C, Alenmyr L, Killander D, Lewis SE, Andersson A, Bucher B, Galzi JL, Sterner O, Bevan S et al.. (2011) TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ(9)-tetrahydrocannabiorcol. Nat Commun, 2: 551. [PMID:22109525]
3. Andersson DA, Gentry C, Moss S, Bevan S. (2008) Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci, 28 (10): 2485-94. [PMID:18322093]
4. Andersson DA, Gentry C, Moss S, Bevan S. (2009) Clioquinol and pyrithione activate TRPA1 by increasing intracellular Zn2+. Proc Natl Acad Sci USA, 106 (20): 8374-9. [PMID:19416844]
5. Andrade EL, Forner S, Bento AF, Leite DF, Dias MA, Leal PC, Koepp J, Calixto JB. (2011) TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury. Am J Physiol Renal Physiol, 300 (5): F1223-34. [PMID:21367919]
6. Andrè E, Campi B, Materazzi S, Trevisani M, Amadesi S, Massi D, Creminon C, Vaksman N, Nassini R, Civelli M et al.. (2008) Cigarette smoke-induced neurogenic inflammation is mediated by alpha,beta-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest, 118 (7): 2574-82. [PMID:18568077]
7. Andrè E, Gatti R, Trevisani M, Preti D, Baraldi PG, Patacchini R, Geppetti P. (2009) Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents. Br J Pharmacol, 158 (6): 1621-8. [PMID:19845671]
8. Balestrini A, Joseph V, Dourado M, Reese RM, Shields SD, Rougé L, Bravo DD, Chernov-Rogan T, Austin CD, Chen H et al.. (2021) A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment. J Exp Med, 218 (4). [PMID:33620419]
9. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A. (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron, 41 (6): 849-57. [PMID:15046718]
10. Bang S, Kim KY, Yoo S, Kim YG, Hwang SW. (2007) Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci, 26 (9): 2516-23. [PMID:17970723]
11. Bang S, Yoo S, Yang TJ, Cho H, Kim YG, Hwang SW. (2010) Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception. Br J Pharmacol, 161 (3): 707-20. [PMID:20880407]
12. Baraldi PG, Preti D, Materazzi S, Geppetti P. (2010) Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. J Med Chem, 53 (14): 5085-107. [PMID:20356305]
13. Barrière DA, Rieusset J, Chanteranne D, Busserolles J, Chauvin MA, Chapuis L, Salles J, Dubray C, Morio B. (2012) Paclitaxel therapy potentiates cold hyperalgesia in streptozotocin-induced diabetic rats through enhanced mitochondrial reactive oxygen species production and TRPA1 sensitization. Pain, 153 (3): 553-61. [PMID:22177224]
14. Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D. (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell, 124 (6): 1269-82. [PMID:16564016]
15. Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Högestätt ED, Julius D, Jordt SE, Zygmunt PM. (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci USA, 102 (34): 12248-52. [PMID:16103371]
16. Bautista DM, Pellegrino M, Tsunozaki M. (2013) TRPA1: A gatekeeper for inflammation. Annu Rev Physiol, 75: 181-200. [PMID:23020579]
17. Bellono NW, Kammel LG, Zimmerman AL, Oancea E. (2013) UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes. Proc Natl Acad Sci USA, 110 (6): 2383-8. [PMID:23345429]
18. Bessac BF, Jordt SE. (2010) Sensory detection and responses to toxic gases: mechanisms, health effects, and countermeasures. Proc Am Thorac Soc, 7 (4): 269-77. [PMID:20601631]
19. Bessac BF, Sivula M, von Hehn CA, Caceres AI, Escalera J, Jordt SE. (2009) Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J, 23 (4): 1102-14. [PMID:19036859]
20. Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt SE. (2008) TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest, 118 (5): 1899-910. [PMID:18398506]
21. Binder A, May D, Baron R, Maier C, Tölle TR, Treede RD, Berthele A, Faltraco F, Flor H, Gierthmühlen J et al.. (2011) Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients. PLoS ONE, 6 (3): e17387. [PMID:21468319]
22. Birrell MA, Belvisi MG, Grace M, Sadofsky L, Faruqi S, Hele DJ, Maher SA, Freund-Michel V, Morice AH. (2009) TRPA1 agonists evoke coughing in guinea pig and human volunteers. Am J Respir Crit Care Med, 180 (11): 1042-7. [PMID:19729665]
23. Bonet IJ, Fischer L, Parada CA, Tambeli CH. (2013) The role of transient receptor potential A 1 (TRPA1) in the development and maintenance of carrageenan-induced hyperalgesia. Neuropharmacology, 65: 206-12. [PMID:23098993]
24. Brierley SM, Castro J, Harrington AM, Hughes PA, Page AJ, Rychkov GY, Blackshaw LA. (2011) TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. J Physiol (Lond.), 589 (Pt 14): 3575-93. [PMID:21558163]
25. Brierley SM, Hughes PA, Page AJ, Kwan KY, Martin CM, O'Donnell TA, Cooper NJ, Harrington AM, Adam B, Liebregts T et al.. (2009) The ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimuli. Gastroenterology, 137 (6): 2084-2095.e3. [PMID:19632231]
26. Brône B, Peeters PJ, Marrannes R, Mercken M, Nuydens R, Meert T, Gijsen HJ. (2008) Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor. Toxicol Appl Pharmacol, 231 (2): 150-6. [PMID:18501939]
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