View source for TRPA (ion channel)

{{Short description|Family of transport proteins}}
{{infobox protein
|Name=[[transient receptor potential cation channel, member A1|transient receptor potential cation channel, subfamily A, member 1]]
|caption=
|image=
|width=
|HGNCid=497
|Symbol=TRPA1
|AltSymbols=ANKTM1
|IUPHAR_id=yes
|EntrezGene=8989
|OMIM=604775
|RefSeq=NM_007332
|UniProt=O75762
|PDB=
|ECnumber=
|Chromosome=8
|Arm=q
|Band=13
|LocusSupplementaryData=
}}
[[File:TRPA Phylogeny.svg|left|thumb|250px|TRPA subfamilies.<ref name="Drosophila menthol sensitivity" /><ref name="Kang 2010" /><ref name="Peng" />]]
'''TRPA''' is a family of [[Transient receptor potential channel|transient receptor potential]] [[ion channel]]s. The TRPA family is made up of 7 subfamilies: TRPA1, TRPA- or TRPA1-like, TRPA5, painless, pyrexia, waterwitch, and HsTRPA.  TRPA1 is the only subfamily widely expressed across animals, while the other subfamilies (collectively referred to as the basal clade) are largely absent in [[deuterostomes]] (and in the case of HsTRPA, only expressed in [[hymenopteran]] insects).<ref name="Kang 2010">{{cite journal | vauthors = Kang K, Pulver SR, Panzano VC, Chang EC, Griffith LC, Theobald DL, Garrity PA | title = Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception | journal = Nature | volume = 464 | issue = 7288 | pages = 597–600 | date = March 2010 | pmid = 20237474 | pmc = 2845738 | doi = 10.1038/nature08848 | bibcode = 2010Natur.464..597K }}</ref><ref name="Drosophila menthol sensitivity">{{cite journal | vauthors = Himmel NJ, Letcher JM, Sakurai A, Gray TR, Benson MN, Cox DN | title = Drosophila menthol sensitivity and the Precambrian origins of transient receptor potential-dependent chemosensation | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 374 | issue = 1785 | pages = 20190369 | date = November 2019 | pmid = 31544603 | pmc = 6790378 | doi = 10.1098/rstb.2019.0369 }}</ref><ref name="Peng">{{cite journal | vauthors = Peng G, Shi X, Kadowaki T | title = Evolution of TRP channels inferred by their classification in diverse animal species | journal = Molecular Phylogenetics and Evolution | volume = 84 | pages = 145–57 | date = March 2015 | pmid = 24981559 | doi = 10.1016/j.ympev.2014.06.016 | bibcode = 2015MolPE..84..145P }}</ref><ref name="Chemoreceptor proteins in the Carib">{{cite journal | vauthors = Kozma MT, Schmidt M, Ngo-Vu H, Sparks SD, Senatore A, Derby CD | title = Chemoreceptor proteins in the Caribbean spiny lobster, Panulirus argus: Expression of Ionotropic Receptors, Gustatory Receptors, and TRP channels in two chemosensory organs and brain | journal = PLOS ONE | volume = 13 | issue = 9 | pages = e0203935 | date = 2018 | pmid = 30240423 | pmc = 6150509 | doi = 10.1371/journal.pone.0203935 | bibcode = 2018PLoSO..1303935K | doi-access = free }}</ref>

[[transient receptor potential cation channel, member A1|TRPA1s]] have been the most extensively studied subfamily; they typically contain 14 N-terminal [[ankyrin]] repeats and are believed to function as mechanical stress, temperature, and chemical sensors. TRPA1 is known to be activated by compounds such as [[isothiocyanate]] (which are the pungent chemicals in substances such as [[mustard oil]] and [[wasabi]]) and [[Michael acceptor]]s (e.g. [[cinnamaldehyde]]). These compounds are capable of forming covalent chemical bonds with the protein's [[cystein]]s.<ref name=Nilius_2007>{{cite journal | vauthors = Nilius B, Owsianik G, Voets T, Peters JA | title = Transient receptor potential cation channels in disease | journal = Physiological Reviews | volume = 87 | issue = 1 | pages = 165–217 | date = January 2007 | pmid = 17237345 | doi = 10.1152/physrev.00021.2006 | url = https://lirias.kuleuven.be/handle/123456789/137085 }}</ref> Non-covalent activators of TRPA1 also exists, such as [[methyl salicylate]], [[menthol]], and the synthetic compound [[PF-4840154]].<ref name="pmid21741838">{{cite journal | vauthors = Ryckmans T, Aubdool AA, Bodkin JV, Cox P, Brain SD, Dupont T, Fairman E, Hashizume Y, Ishii N, Kato T, Kitching L, Newman J, Omoto K, Rawson D, Strover J | display-authors = 6 | title = Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel | journal = Bioorganic & Medicinal Chemistry Letters | volume = 21 | issue = 16 | pages = 4857–9 | date = August 2011 | pmid = 21741838 | doi = 10.1016/j.bmcl.2011.06.035 }}</ref><ref name="Drosophila menthol sensitivity" /><ref>{{cite book | vauthors = Zygmunt PM, Högestätt ED | title = Mammalian Transient Receptor Potential (TRP) Cation Channels | chapter = TRPA1 | series = Handbook of Experimental Pharmacology | volume = 222 | pages = 583–630 | date = 2014 | pmid = 24756722 | doi = 10.1007/978-3-642-54215-2_23 | isbn = 978-3-642-54214-5 }}</ref>

The thermal sensitivity of TRPAs varies by species. For example, TRPA1 functions as a high-temperature sensor in insects and snakes, but as a cold sensor in mammals.<ref>{{cite journal | vauthors = Panzano VC, Kang K, Garrity PA | title = Infrared snake eyes: TRPA1 and the thermal sensitivity of the snake pit organ | journal = Science Signaling | volume = 3 | issue = 127 | pages = pe22 | date = June 2010 | pmid = 20571127 | doi = 10.1126/scisignal.3127pe22 | s2cid = 13504270 }}</ref> The basal TRPAs have evolved some degree of thermal sensitivity as well: painless and pyrexia function in high-temperature sensing in [[Drosophila melanogaster]], and the honey bee HsTRPA underwent [[neofunctionalization]] following its divergence from waterwitch, gaining function as a high-temperature sensor.<ref>{{cite journal | vauthors = Kohno K, Sokabe T, Tominaga M, Kadowaki T | title = Honey bee thermal/chemical sensor, AmHsTRPA, reveals neofunctionalization and loss of transient receptor potential channel genes | journal = The Journal of Neuroscience | volume = 30 | issue = 37 | pages = 12219–29 | date = September 2010 | pmid = 20844118 | pmc = 6633439 | doi = 10.1523/JNEUROSCI.2001-10.2010 }}</ref>

TRPA1s promiscuity with respect to sensory modality has been the source of controversy, particularly when considering its ability to detect cold.<ref>{{cite journal | vauthors = Caspani O, Heppenstall PA | title = TRPA1 and cold transduction: an unresolved issue? | journal = The Journal of General Physiology | volume = 133 | issue = 3 | pages = 245–9 | date = March 2009 | pmid = 19237589 | pmc = 2654088 | doi = 10.1085/jgp.200810136 }}</ref> More recent work has alternatively (or additionally) proposed that [[reactive oxygen species]] activate TRPA1, across species.<ref>{{cite journal | vauthors = Arenas OM, Zaharieva EE, Para A, Vásquez-Doorman C, Petersen CP, Gallio M | title = Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for animal nociception | journal = Nature Neuroscience | volume = 20 | issue = 12 | pages = 1686–1693 | date = December 2017 | pmid = 29184198 | pmc = 5856474 | doi = 10.1038/s41593-017-0005-0 }}</ref><ref>{{cite journal | vauthors = Miyake T, Nakamura S, Zhao M, So K, Inoue K, Numata T, Takahashi N, Shirakawa H, Mori Y, Nakagawa T, Kaneko S | display-authors = 6 | title = Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS | journal = Nature Communications | volume = 7 | pages = 12840 | date = September 2016 | pmid = 27628562 | pmc = 5027619 | doi = 10.1038/ncomms12840 | bibcode = 2016NatCo...712840M }}</ref>

== References ==
{{Reflist}}

== External links ==
* {{MeshName|TRPA1+protein,+human}}
* {{cite web | url = http://www.trpchannel.org | title = TRIP Database | work = a manually curated database of protein-protein interactions for mammalian TRP channels}}

{{Ion channels|g4}}
{{Transient receptor potential channel modulators}}

[[Category:Membrane proteins]]
[[Category:Ion channels]]