Target has curated data in GtoImmuPdb
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Functional Characteristics
- Ion Selectivity and Conductance
- Voltage Dependence
- Rank order lists
- Activators
- Inhibitors
- Gating Inhibitors
- Antagonists
- Channel Blockers
- Immunopharmacology Comments
- Immuno Cell Type Associations
- Tissue Distribution
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Gene Expression and Pathophysiology
- Biologically Significant Variants
- General Comments
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| 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 |
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| 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 |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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]. |
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| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Gating inhibitors
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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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| Note that expression is upregulated by de-ubiquitination by the tumor suppressor (ubiquitin hydrolase) CYLD. | ||||||||
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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. |
References
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]
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