Transient receptor potential cation channel subfamily A member 1
Also known as: ANKTM1, TRPA1
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. 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. 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. Electrophilic ligands activate TRPA1 by interacting with critical N-terminal Cys residues in a covalent manner. Non-electrophile agonists bind at distinct sites in the transmembrane domain to promote channel activation. Also acts as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds (By similarity).
Classification
- Family (Pfam)
- PF00023 Ank, PF12796 Ank_2, PF13637 Ank_4, PF00520 Ion_trans
- InterPro
- Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ion_trans_dom, TRP_cation_channel
- Functional cluster
- Serine/Threonine Protein Kinases
Experimental structures · PDB · 17
- 3J9P EM 4.24A
- 6HC8 X-ray 1.90A
- 6PQO EM 2.88A
- 6PQP EM 3.06A
- 6PQQ EM 2.81A
- 6V9V EM 2.60A
- 6V9W EM 3.10A
- 6V9X EM 3.30A
- 6V9Y EM 3.60A
- 6WJ5 EM 3.60A
- 6X2J EM 3.00A
- 7JUP EM 3.05A
- … and 5 more
A predicted model is available from AlphaFold.
Gene Ontology · 34
- GO:0016324 apical plasma membrane
- GO:0030424 axon
- GO:0005886 plasma membrane
- GO:0032421 stereocilium bundle
- GO:0005262 calcium channel activity
- GO:0015267 channel activity
- GO:0042802 identical protein binding
- GO:0015278 intracellularly gated calcium channel activity
- GO:1990760 osmolarity-sensing monoatomic cation channel activity
- GO:0097604 temperature-gated cation channel activity
- GO:0005245 voltage-gated calcium channel activity
- GO:0097553 calcium ion transmembrane import into cytosol
- GO:0070588 calcium ion transmembrane transport
- GO:0007166 cell surface receptor signaling pathway
- GO:0071313 cellular response to caffeine
- GO:0071244 cellular response to carbon dioxide
- GO:0070417 cellular response to cold
- GO:0071240 cellular response to food
- GO:0034605 cellular response to heat
- GO:0070301 cellular response to hydrogen peroxide
- GO:0097237 cellular response to toxic substance
- GO:0050968 detection of chemical stimulus involved in sensory perception of pain
- GO:0050974 detection of mechanical stimulus involved in sensory perception
- GO:0006874 intracellular calcium ion homeostasis
- GO:0006811 monoatomic ion transport
- GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
- GO:1903793 positive regulation of monoatomic anion transport
- GO:0051289 protein homotetramerization
- GO:1903522 regulation of blood circulation
- GO:0098908 regulation of neuronal action potential
- GO:0009409 response to cold
- GO:0019233 sensory perception of pain
- GO:0050955 thermoception
- GO:0014832 urinary bladder smooth muscle contraction
Disease associations
Drugs targeting this protein · 3
- BUTAMBEN inhibitor
- MENTHOL opener
- BUTAMBEN PICRATE inhibitor
Related proteins · sequence + function similarity
- Transient receptor potential cation channel subfamily A member 1 0.99
- Transient receptor potential cation channel subfamily A member 1 0.98
- Transient receptor potential cation channel subfamily A member 1 0.79
- Transient receptor potential cation channel subfamily A member 1 homolog 0.79
- Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit C 0.71
- Ankyrin repeat and SOCS box protein 7 0.70
- Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit B 0.70
- Ankyrin repeat and SOCS box protein 7 0.70
- Ankyrin repeat and SOCS box protein 7 0.70
- Transient receptor potential cation channel subfamily V member 3 0.70
- Ankyrin repeat and SOCS box protein 7 0.70
- Transient receptor potential cation channel subfamily V member 3 0.70
Co-cited proteins · studied together in the literature
- Transient receptor potential cation channel subfamily A member 1 3 shared papers
- Transient receptor potential cation channel subfamily A member 1 1 shared papers
- Wasabi receptor toxin 1 shared papers
Literature · 20 cited papers
- A Non-covalent Ligand Reveals Biased Agonism of the TRPA1 Ion Channel. Neuron · 2021
- Irritant-evoked activation and calcium modulation of the TRPA1 receptor. Nature · 2020
- Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel. Neuron · 2020
- A cell-penetrating scorpion toxin enables mode-specific modulation of TRPA1 and pain. Cell · 2019
- N-Cinnamoylanthranilates as human TRPA1 modulators: structure-activity relationships and channel binding sites. Eur. J. Med. Chem. · 2019
- The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1. J. Gen. Physiol. · 2016
- PMID 26200340 Nature · 2015
- Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature · 2015
- Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain. Proc. Natl. Acad. Sci. U.S.A. · 2014
- Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels. Cough · 2012
- TRPA1 underlies a sensing mechanism for O2. Nat. Chem. Biol. · 2011
- Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation. Pain · 2011
- … and 8 more in the literature graph