Editing Transient receptor potential channel (section)

== Families ==
[[File:TRP Channel Phylogeny.svg|right|thumb|500px|TRP channel groups and families.]]

In the animal TRP superfamily there are currently 9 proposed families split into two groups, each family containing a number of subfamilies.<ref name="TRP_review" /> Group one consists of TRPC, TRPV, TRPVL, TRPA, TRPM, TRPS, and TRPN, while group two contains TRPP and TRPML. There is an additional family labeled TRPY that is not always included in either of these groups. All of these sub-families are similar in that they are molecular sensing, non-selective cation channels that have six transmembrane segments, however, each sub-family is unique and shares little structural homology with one another. This uniqueness gives rise to the various sensory perception and regulation functions that TRP channels have throughout the body. Group one and group two vary in that both TRPP and TRPML of group two have a much longer extracellular loop between the S1 and S2 transmembrane segments. Another differentiating characteristic is that all the group one sub-families either contain an N-terminal intracellular ankyrin repeat sequence, a C-terminal TRP domain sequence, or both—whereas both group two sub-families have neither.<ref name="Kadowaki_evodyn">{{cite journal | vauthors = Kadowaki T | title = Evolutionary dynamics of metazoan TRP channels | journal = Pflügers Archiv | volume = 467 | issue = 10 | pages = 2043–53 | date = October 2015 | pmid = 25823501 | doi = 10.1007/s00424-015-1705-5 | s2cid = 9190224 }}</ref> Below are members of the sub-families and a brief description of each:

===TRPA===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa<ref>{{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>
|-
|rowspan="7" |TRPA
|[[TRPA1]]
|[[Vertebrates]], [[arthropods]], and [[molluscs]]
|-
|TRPA-like
|[[Choanoflagellates]], [[cnidarians]], [[nematodes]], arthropods (only crustaceans and myriapods), molluscs, and [[echinoderms]]
|-
|TRPA5
|rowspan="4" |Arthropods (only crustaceans and insects)
|-
|painless
|-
|pyrexia
|-
|waterwitch
|-
|HsTRPA
|Specific to [[hymenopteran]] insects
|}
TRPA, A for "ankyrin", is named for the large amount of ankyrin repeats found near the N-terminus.<ref name=":4">{{cite journal | vauthors = Moran MM, McAlexander MA, Bíró T, Szallasi A | title = Transient receptor potential channels as therapeutic targets | journal = Nature Reviews. Drug Discovery | volume = 10 | issue = 8 | pages = 601–20 | date = August 2011 | pmid = 21804597 | doi = 10.1038/nrd3456 | s2cid = 8809131 }}</ref> TRPA is primarily found in afferent nociceptive nerve fibers and is associated with the amplification of pain signaling as well as cold pain hypersensitivity. These channels have been shown to be both mechanical receptors for pain and chemosensors activated by various chemical species, including isothiocyanates (pungent chemicals in substances such as mustard oil and wasabi), cannabinoids, general and local analgesics, and cinnamaldehyde.<ref name=":3" />

While TRPA1 is expressed in a wide variety of animals, a variety of other TRPA channels exist outside of vertebrates.  TRPA5, painless, pyrexia, and waterwitch are distinct phylogenetic branches within the TRPA clade, and are only evidenced to be expressed in crustaceans and insects,<ref name="Kadowaki_evodyn"/> while HsTRPA arose as a Hymenoptera-specific duplication of waterwitch.<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> Like TRPA1 and other TRP channels, these function as ion channels in a number of sensory systems. TRPA- or TRPA1-like channels also exists in a variety of species as a phylogenetically distinct clade, but these are less well understood.<ref name="Drosophila menthol sensitivity"/>

===TRPC===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa<ref name="Peng" /><ref>{{cite journal | vauthors = French AS, Meisner S, Liu H, Weckström M, Torkkeli PH | title = Transcriptome analysis and RNA interference of cockroach phototransduction indicate three opsins and suggest a major role for TRPL channels | journal = Frontiers in Physiology | volume = 6 | pages = 207 | date = 2015 | pmid = 26257659 | pmc = 4513288 | doi = 10.3389/fphys.2015.00207 | doi-access = free }}</ref><ref name="Himmel2">{{cite journal |vauthors=Himmel NJ, Gray TR, Cox DN |date=July 2020 |title=Phylogenetics Identifies Two Eumetazoan TRPM Clades and an Eighth TRP Family, TRP Soromelastatin (TRPS) |journal=Molecular Biology and Evolution |volume=37 |issue=7 |pages=2034–2044 |doi=10.1093/molbev/msaa065 |pmc=7306681 |pmid=32159767 |doi-access=free}}</ref>
|-
|rowspan="11" |TRPC
|[[TRPC1]]
|rowspan="7" |Vertebrates
|-
|[[TRPC2]]
|-
|[[TRPC3]]
|-
|[[TRPC4]]
|-
|[[TRPC5]]
|-
|[[TRPC6]]
|-
|[[TRPC7]]
|-
|TRP
|rowspan="3" |Arthropods
|-
|TRPgamma
|-
|TRPL
|-
|Unknown
|Choanoflagellates, cnidarians, [[xenacoelomorpha|xenacoelomorphs]], [[lophotrochozoa]]ns, and nematodes
|}
TRPC, C for "canonical", is named for being the most closely related to ''Drosophila'' TRP, the namesake of TRP channels.  The phylogeny of TRPC channels has not been resolved in detail, but they are present across animal taxa.  There are actually only six TRPC channels expressed in humans because TRPC2 is found to be expressed solely in mice and is considered a [[Pseudogene|pseudo-gene]] in humans; this is partly due to the role of TRPC2 in detecting pheromones, which mice have an increased ability compared to humans. Mutations in TRPC channels have been associated with respiratory diseases along with [[focal segmental glomerulosclerosis]] in the kidneys.<ref name=":3">{{Cite book|title=TRP channels as therapeutic targets : from basic science to clinical use|others=Szallasi, Arpad, 1958-, McAlexander, M. Allen|isbn=9780124200791|location=Amsterdam [Netherlands]|oclc=912315205| vauthors = Szallasi A |date=2015-04-09}}</ref> All TRPC channels are activated either by [[phospholipase C]] (PLC) or [[Diglyceride|diacyglycerol]] (DAG).

===TRPML===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa<ref name="Peng" /><ref name="Garcia TRML">{{cite book | vauthors = García-Añoveros J, Wiwatpanit T | chapter = TRPML2 and Mucolipin Evolution | title = Mammalian Transient Receptor Potential (TRP) Cation Channels | series = Handbook of Experimental Pharmacology | volume = 222 | pages = 647–58 | date = 2014 | pmid = 24756724 | doi = 10.1007/978-3-642-54215-2_25 | isbn = 978-3-642-54214-5 }}</ref>
|-
| rowspan="4" |TRPML
|Unknown
| Cnidarians, basal vertebrates, [[tunicates]], [[cephalochordates]], [[hemichordates]], echinoderms, arthropods, and nematodes
|-
|[[MCOLN1|TRPML1]]
| rowspan="3" |Specific to jawed vertebrates
|-
|[[MCOLN2|TRPML2]]
|-
|[[MCOLN3|TRPML3]]
|}
TRPML, ML for "mucolipin", gets its name from the neurodevelopmental disorder [[Mucolipidosis type IV|mucolipidosis IV]]. Mucolipidosis IV was first discovered in 1974 by E.R. Berman who noticed abnormalities in the eyes of an infant.<ref>{{cite journal | vauthors = Berman ER, Livni N, Shapira E, Merin S, Levij IS | title = Congenital corneal clouding with abnormal systemic storage bodies: a new variant of mucolipidosis | journal = The Journal of Pediatrics | volume = 84 | issue = 4 | pages = 519–26 | date = April 1974 | pmid = 4365943 | doi = 10.1016/s0022-3476(74)80671-2 }}</ref> These abnormalities soon became associated with mutations to the MCOLN1 gene which encodes for the TRPML1 ion channel. TRPML is still not highly characterized.  The three known vertebrate copies are restricted to jawed vertebrates, with some exceptions (e.g. ''[[Xenopus tropicalis]]'').<ref name="Garcia TRML" />

===TRPM===
{| class="wikitable"
!Family !!Sub-Family !! Known Taxa
|-
|rowspan="2" |TRPM
|Alpha/α (inc. TRPM1, 3, 6, and 7)
| rowspan="2"|All [[choanoflagellate]]s and [[eumetazoa]] (except [[tardigrades]])
|-
|Beta/β (inc. TRPM2, 4, 5, and 8)
|}
TRPM, M for "melastatin", was found during a comparative genetic analysis between benign [[Nevus|nevi]] and malignant nevi (melanoma).<ref name=":4" /> Mutations within TRPM channels have been associated with hypomagnesemia with secondary hypocalcemia. TRPM channels have also become known for their cold-sensing mechanisms, such is the case with TRPM8.<ref name=":3" />  Comparative studies have shown that the functional domains and critical amino acids of TRPM channels are highly conserved across species.<ref>{{cite journal |vauthors=Mederos y Schnitzler M, Wäring J, Gudermann T, Chubanov V |date=May 2008 |title=Evolutionary determinants of divergent calcium selectivity of TRPM channels |journal=FASEB Journal |volume=22 |issue=5 |pages=1540–51 |doi=10.1096/fj.07-9694com |doi-access=free |pmid=18073331 |s2cid=25474094}}</ref><ref name="Drosophila menthol sensitivity" /><ref>{{cite journal |vauthors=Iordanov I, Tóth B, Szollosi A, Csanády L |date=April 2019 |title=Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates |journal=eLife |volume=8 |doi=10.7554/eLife.44556 |pmc=6461439 |pmid=30938679 |doi-access=free }}</ref>

[[Phylogenetics]] has shown that TRPM channels are split into two major clades, αTRPM and βTRPM.<ref name="Drosophila menthol sensitivity" /><ref name="Himmel2" /> αTRPMs include vertebrate TRPM1, TRPM3, and the "chanzymes" TRPM6 and TRPM7, as well as the only insect TRPM channel, among others. βTRPMs include, but are not limited to, vertebrate TRPM2, TRPM4, TRPM5, and TRPM8 (the cold and menthol sensor).  Two additional major clades have been described: TRPMc, which is present only in a variety of arthropods,<ref name="Himmel2" /> and a basal clade,<ref name="Peng" /><ref name="Drosophila menthol sensitivity" /> which has since been proposed to be a distinct and separate TRP channel family (TRPS).<ref name="Himmel2" />

===TRPN===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa<ref name="Schuler">{{cite journal | vauthors = Schüler A, Schmitz G, Reft A, Özbek S, Thurm U, Bornberg-Bauer E | title = The Rise and Fall of TRP-N, an Ancient Family of Mechanogated Ion Channels, in Metazoa | journal = Genome Biology and Evolution | volume = 7 | issue = 6 | pages = 1713–27 | date = June 2015 | pmid = 26100409 | pmc = 4494053 | doi = 10.1093/gbe/evv091 }}</ref><ref name="Peng" />
|-
|TRPN
|TRPN/nompC
|Placozoans, cnidarians, nematodes, arthropods, molluscs, [[annelids]], and vertebrates (excluding amniotes)
|}
TRPN was originally described in ''Drosophila melanogaster'' and ''Caenorhabditis elegans'' as nompC, a mechanically gated ion channel.<ref>{{cite journal | vauthors = Walker RG, Willingham AT, Zuker CS | title = A Drosophila mechanosensory transduction channel | journal = Science | volume = 287 | issue = 5461 | pages = 2229–34 | date = March 2000 | pmid = 10744543 | doi = 10.1126/science.287.5461.2229 | bibcode = 2000Sci...287.2229W }}</ref><ref name="Schuler" /> Only a single TRPN, N for "no mechanoreceptor potential C," or "nompC", is known to be broadly expressed in animals (although some Cnidarians have more), and is notably only a [[pseudogene]] in [[amniote]] vertebrates.<ref name="Schuler" /><ref name="Peng" /> Despite TRPA being named for ankyrin repeats, TRPN channels are thought to have the most of any TRP channel, typically around 28, which are highly conserved across taxa <ref name="Schuler" /> Since its discovery, ''Drosophila'' nompC has been implicated in mechanosensation (including mechanical stimulation of the cuticle and sound detection) and cold [[nociception]].<ref name="Himmel_InvNoc">{{cite book | vauthors =Himmel N, Patel A, Cox D | chapter = Invertebrate Nociception | title = The Oxford Research Encyclopedia of Neuroscience |date=March 2017 |doi=10.1093/acrefore/9780190264086.013.166 |isbn=9780190264086 }}</ref>

===TRPP===
{| class="wikitable"
!Family
!Sub-Family<ref name="Peng" /><ref name="Montell_2001" /><ref name="Gallio_Brivido">{{cite journal | vauthors = Gallio M, Ofstad TA, Macpherson LJ, Wang JW, Zuker CS | title = The coding of temperature in the Drosophila brain | journal = Cell | volume = 144 | issue = 4 | pages = 614–24 | date = February 2011 | pmid = 21335241 | pmc = 3336488 | doi = 10.1016/j.cell.2011.01.028 | doi-access = free }}</ref><ref name="TRP_review">{{cite journal | vauthors = Himmel NJ, Cox DN | title = Transient receptor potential channels: current perspectives on evolution, structure, function and nomenclature | journal = Proceedings. Biological Sciences | volume = 287 | issue = 1933 | pages = 20201309 | date = August 2020 | pmid = 32842926 | pmc = 7482286 | doi = 10.1098/rspb.2020.1309 | doi-access = free }}</ref>
!Known Taxa<ref name="BC 2018">{{cite journal | vauthors = Bezares-Calderón LA, Berger J, Jasek S, Verasztó C, Mendes S, Gühmann M, Almeda R, Shahidi R, Jékely G | display-authors = 6 | title = Neural circuitry of a polycystin-mediated hydrodynamic startle response for predator avoidance | journal = eLife | volume = 7 | date = December 2018 | pmid = 30547885 | pmc = 6294549 | doi = 10.7554/eLife.36262 | doi-access = free }}</ref><ref name="Gallio_Brivido" />
|-
|rowspan="3" |TRPP
|PKD1-like
|Animals (excluding arthropods)
|-
|PKD2-like
|Animals
|-
|Brividos
|Insects
|}
[[TRPP]], P for "polycistin", is named for [[Autosomal dominant polycystic kidney disease|polycystic kidney disease]], which is associated with these channels.<ref name=":4" /> These channels are also referred to as PKD (polycistic kidney disease) ion channels.

PKD2-like genes (examples include [[TRPP2]], [[TRPP3]], and [[TRPP5]]) encode canonical TRP channels.  PKD1-like genes encode much larger proteins with 11 transmembrane segments, which do not have all the features of other TRP channels.  However, 6 of the transmebrane segments of PKD1-like proteins have substantial sequence homology with TRP channels, indicating they may simply have diversified greatly from other closely related proteins.<ref name="BC 2018" />

Insects have a third sub-family of TRPP, called brividos, which participate in cold sensing.<ref name="Gallio_Brivido" /><ref name="TRP_review" />

===TRPS===
TRPS, S for Soromelastatin, was named as it forms a sister group to TRPM. TRPS is broadly present in animals, but notably absent in vertebrates and insects (among others).<ref name="Himmel2" /> TRPS has not yet been well described functionally, though it is known that the ''C. elegans'' TRPS, known as CED-11, is a calcium channel which participates in [[apoptosis]].<ref>{{cite journal | vauthors = Driscoll K, Stanfield GM, Droste R, Horvitz HR | title = Presumptive TRP channel CED-11 promotes cell volume decrease and facilitates degradation of apoptotic cells in ''Caenorhabditis elegans'' | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 33 | pages = 8806–8811 | date = August 2017 | pmid = 28760991 | pmc = 5565440 | doi = 10.1073/pnas.1705084114 | doi-access = free | bibcode = 2017PNAS..114.8806D }}</ref>

===TRPV===
{| class="wikitable"
!Family
!Sub-Family
!Known Taxa <ref name="Peng" /><ref>{{cite journal | vauthors = Cattaneo AM, Bengtsson JM, Montagné N, Jacquin-Joly E, Rota-Stabelli O, Salvagnin U, Bassoli A, Witzgall P, Anfora G | display-authors = 6 | title = TRPA5, an Ankyrin Subfamily Insect TRP Channel, is Expressed in Antennae of Cydia pomonella (Lepidoptera: Tortricidae) in Multiple Splice Variants | journal = Journal of Insect Science | volume = 16 | issue = 1 | pages = 83 | date = 2016 | pmid = 27638948 | pmc = 5026476 | doi = 10.1093/jisesa/iew072 }}</ref>
|-
|rowspan="8" |TRPV
|[[Nanchung]]
|rowspan="2" |[[Placozoans]], cnidarians, nematodes, annelids, molluscs, and arthropods (possibly excluding [[arachnids]])
|-
|[[Inactive]]
|-
|[[TRPV1]]
|rowspan="6" |Specific to vertebrates
|-
|[[TRPV2]]
|-
|[[TRPV3]]
|-
|[[TRPV4]]
|-
|[[TRPV5]]
|-
|[[TRPV6]]
|-
|}
TRPV, V for "vanilloid", was originally discovered in ''Caenorhabditis elegans'', and is named for the vanilloid chemicals that activate some of these channels.<ref name="Montell_2001">{{cite journal | vauthors = Montell C | title = Physiology, phylogeny, and functions of the TRP superfamily of cation channels | journal = Science's STKE | volume = 2001 | issue = 90 | pages = re1 | date = July 2001 | pmid = 11752662 | doi = 10.1126/stke.2001.90.re1 | s2cid = 37074808 }}</ref><ref>{{cite journal | vauthors = Colbert HA, Smith TL, Bargmann CI | title = OSM-9, a novel protein with structural similarity to channels, is required for olfaction, mechanosensation, and olfactory adaptation in Caenorhabditis elegans | journal = The Journal of Neuroscience | volume = 17 | issue = 21 | pages = 8259–69 | date = November 1997 | pmid = 9334401 | pmc = 6573730 | doi = 10.1523/JNEUROSCI.17-21-08259.1997 }}</ref> These channels have been made famous for their association with molecules such as [[capsaicin]] (a TRPV1 agonist).<ref name=":3" />  In addition to the 6 known vertebrate paralogues, 2 major clades are known outside of the deterostomes: nanchung and Iav. Mechanistic studies of these latter clades have been largely restricted to ''Drosophila'', but phylogenetic analyses has placed a number of other genes from Placozoa, Annelida, Cnidaria, Mollusca, and other arthropods within them.<ref name="Peng" /><ref>{{cite journal | vauthors = Gong Z, Son W, Chung YD, Kim J, Shin DW, McClung CA, Lee Y, Lee HW, Chang DJ, Kaang BK, Cho H, Oh U, Hirsh J, Kernan MJ, Kim C | display-authors = 6 | title = Two interdependent TRPV channel subunits, inactive and Nanchung, mediate hearing in Drosophila | journal = The Journal of Neuroscience | volume = 24 | issue = 41 | pages = 9059–66 | date = October 2004 | pmid = 15483124 | pmc = 6730075 | doi = 10.1523/JNEUROSCI.1645-04.2004 }}</ref><ref>{{cite journal | vauthors = Kim J, Chung YD, Park DY, Choi S, Shin DW, Soh H, Lee HW, Son W, Yim J, Park CS, Kernan MJ, Kim C | display-authors = 6 | title = A TRPV family ion channel required for hearing in Drosophila | journal = Nature | volume = 424 | issue = 6944 | pages = 81–4 | date = July 2003 | pmid = 12819662 | doi = 10.1038/nature01733 | s2cid = 4426696 | bibcode = 2003Natur.424...81K }}</ref> TRPV channels have also been described in protists.<ref name="Peng" />

===TRPVL===
TRPVL has been proposed to be a sister clade to TRPV, and is limited to the cnidarians ''[[Nematostella vectensis]]'' and ''[[Hydra magnipapillata]]'', and the annelid ''[[Capitella teleta]]''.<ref name="Peng" /> Little is known concerning these channels.

===TRPY===
TRPY, Y for "yeast", is highly localized to the yeast vacuole, which is the functional equivalent of a lysosome in a mammalian cell, and acts as a mechanosensor for vacuolar osmotic pressure. Patch clamp techniques and hyperosmotic stimulation have illustrated that TRPY plays a role in intracellular calcium release.<ref>{{cite journal | vauthors = Dong XP, Wang X, Xu H | title = TRP channels of intracellular membranes | journal = Journal of Neurochemistry | volume = 113 | issue = 2 | pages = 313–28 | date = April 2010 | pmid = 20132470 | pmc = 2905631 | doi = 10.1111/j.1471-4159.2010.06626.x }}</ref> Phylogenetic analysis has shown that TRPY1 does not form a part with the other metazoan TRP groups one and two, and is suggested to have evolved after the divergence of metazoans and fungi.<ref name="Kadowaki_evodyn"/> Others have indicated that TRPY are more closely related to TRPP.<ref>{{cite journal | vauthors = Palovcak E, Delemotte L, Klein ML, Carnevale V | title = Comparative sequence analysis suggests a conserved gating mechanism for TRP channels | journal = The Journal of General Physiology | volume = 146 | issue = 1 | pages = 37–50 | date = July 2015 | pmid = 26078053 | pmc = 4485022 | doi = 10.1085/jgp.201411329 }}</ref>