TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.4.1.1









Transient receptor potential (TRP) protein.  Assembles in vivo as a homomultimeric channel, not as a heteromeric channel with TrpL as the subunit (Katz et al. 2013).

Eukaryota
Metazoa
TRP protein of Drosophila melanogaster (P19334)
*1.A.4.1.2









TRP7 receptor-activated capacitative Ca2+ entry channel

Eukaryota
Metazoa
TRP7 of Mus musculus (Q9WVC5)
*1.A.4.1.3









TRPC1 store-operated Ca2+ channel (Liu et al., 2003) (activated by the metabotropic [G- protein-dependent] glutamate receptor, mGluR1) (Kim et al., 2003) (controls salivary gland fluid secretion in mice (Liu et al., 2007a).  Constitutively active TRPC1/C4-dependent background Ca2+ entry fine-tunes Ca2+ cycling in beating adult cardiomyocytes. Double TRPC1/C4-gene inactivation protects against development of maladaptive cardiac remodelling without altering cardiac or extracardiac functions contributing to this pathogenesis (Camacho Londoño et al. 2015).

Eukaryota
Metazoa
TRPC1 of Homo sapiens (P48995)
*1.A.4.1.4









TRPC3 store-operated non-selective cation channel (activated by thapsigargin and 2 acyl glycerol; forms a heteromeric channel with TrpC1, TC #1.A.4.1.3) (Liu et al., 2005).  A  structural model of the TRPC3 permeation pathway based on a sodium channel (TC# 1.A.1.14.5) with a localized selectivity filter and an occluding gate with evidence for allosteric coupling between the gate and the selectivity filter has been proposed (Ko et al. 2009; Lichtenegger et al. 2013). The channel may have a large internal chamber surrounded by signal sensing antennas (Mio et al. 2007).

Eukaryota
Metazoa
TRPC3 of Homo sapiens (Q13507)
*1.A.4.1.5









transient receptor potential canonical-6, TRPC6,  a non-selective cation channel that is directly activated by diacylglycerol (DAG (Szabó et al. 2015). Mutation causes a particularly aggressive form of familial focal segmental glomerulosclerosis (Winn et al., 2005; Mukerji et al., 2007). 

Eukaryota
Metazoa
TRPC6 of Homo sapiens (Q9Y210)
*1.A.4.1.6









Sperm TRP-3 (SPE-41) Ca2+-permeable channel. Translocated from vesicles to the plasma membrane upon sperm activation in a process dependent on the 4TMS SPE-38 protein (8.A.36.1.1) (Singaravelu et al., 2012) during sperm-egg interactions leading to fertilization (Xu et al., 2003).

Eukaryota
Metazoa
TRP-3 of Caenorhabditis elegans (AAQ22724)
*1.A.4.1.7









Short transient receptor channel 5 (TrpC5 or Htrp5) (transports Ca2+ and Sr2+ in the presence of Orai1 and STIM1 (TC# 1.A.52.1.1) (Ma et al., 2008). It is a cold-transducer in the peripheral nervous system (Zimmermann et al., 2011).

Eukaryota
Metazoa
TrpC5 of Homo sapiens (Q9UL62)
*1.A.4.1.8









TrpL (Trp-like), isoform A (1124 aas).  Assembles in vivo as homomultimeric channes, not as heteromeric channels with Trp as had been reported (Katz et al. 2013).

Eukaryota
Metazoa
TrpL of Drosophila melanogaster (P48994)
*1.A.4.1.9









Trp-1 isoform channel; controls nicotne-dependent behavior (Xiao and Xu 2009). TRPC orthologues TRP-1 and -2 genetically complement the loss of syndecan by suppressing neuronal guidance and locomotory defects related to increases in neuronal calcium levels. The widespread and conserved syndecan-TRPC axis therefore fine tunes cytoskeletal organization and cell behavior (Gopal et al. 2015).

Eukaryota
Metazoa
Trp-1 of Caenorhabditis elegans
*1.A.4.1.10









Trp-2 channel; controls nicotine-dependent behavior (Xiao and Xu 2009).  The TRPC orthologues TRP-1 and -2 genetically complement the loss of syndecan by suppressing neuronal guidance and locomotory defects related to increases in neuronal calcium levels. The widespread and conserved syndecan-TRPC axis therefore fine tunes cytoskeletal organization and cell behavior (Gopal et al. 2015).

Eukaryota
Metazoa
Trp-2 of Caenorhabditis elegans
*1.A.4.1.11









TRP channel homologue, Trp1, of 766 aas and 6 - 9 TMSs.  Contains Ankyrin - PKD1 - TrpC channel domains.  Exhibits properties of mammalian signal transduction Trp channels (Arias-Darraz et al. 2015).

Eukaryota
Viridiplantae
TRP channel homologue of Chlamydomonas reinhardtii (Chlamydomonas smithii)
*1.A.4.1.12









TrpC4 of 977aas.  In epidermal keratinocytes, a syndecan-TRPC4 complex controls adhesion, adherens junction composition, and early differentiation in vivo and in vitro (Gopal et al. 2015).  Constitutively active TRPC1/C4-dependent background Ca2+ entry fine-tunes Ca2+ cycling in beating adult cardiomyocytes. Double TRPC1/C4-gene inactivation protects against development of maladaptive cardiac remodelling without altering cardiac or extracardiac functions contributing to this pathogenesis (Camacho Londoño et al. 2015).

Eukaryota
Metazoa
TrpC4 of Homo sapiens
*1.A.4.1.13









Transient receptor potential ion channel protein, TRP6, OF 2341 aas and 6 - 9 TMSs.

Eukaryota
Viridiplantae
TRP6 OF Chlamydomonas reinhardtii (Chlamydomonas smithii)
*1.A.4.1.14









Flagellar associated calcium channel protein of 1,729 aas, FAP148 (Wheeler and Brownlee 2008).

FAP148 of Chlamydomonas reinhardtii
*1.A.4.2.1









Vanilloid receptor subtype 1 (VR1 or TRPV1) (noxious, heat-sensitive [opens with increasing temperatures; e.g., >42°C]; also sensitive to acidic pH and voltage; serves as the receptor for the alkaloid irritant, capsaicin, for resiniferatoxin and for endo-cannabinoids (Murillo-Rodriguez et al. 2017). It is regulated by bradykinin and prostaglandin E2) (contains a C-terminal region, adjacent to the channel gate, that determines the coupling of stimulus sensing and channel opening (Garcia-Sanz et al., 2007; Matta and Ahern, 2007). Activated and sensitized by local anesthetics in sensory neurons (Leffler et al., 2008). A bivalent tarantula toxin activates the capsaicin receptor (TRPV1) by targeting the outer pore domain (Bohlen et al., 2010). Single-channel properties of TRPV1 are modulated by phosphorylation (Studer and McNaughton, 2010). TRPV1 mediates an itch associated response (Kim et al., 2011). The thermosensitive TRP channel pore turret is part of the temperature activation apparatus (Yang et al., 2010). Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels have been identified (Yao et al., 2011). TRPV1 opening is associated with major structural rearrangements in the outer pore, including the pore helix and selectivity filter, as well as pronounced dilation of a hydrophobic constriction at the lower gate, suggesting a dual gating mechanism (Cao et al. 2013). Allosteric coupling between upper and lower gates may account for modulation exhibited by TRPV1 and other TRP channels (Liao et al. 2013).  Regulates longevity and metabolism by neuropeptides in mice (Riera et al. 2014).

Eukaryota
Metazoa
VR1 of Rattus norvegicus
*1.A.4.2.2









Stretch-inhibitable non-selective cation channel, SIC

Eukaryota
Metazoa
SIC of Rattus norvegicus
*1.A.4.2.3









Vitamin D-responsive, apical, epithelial Ca2+ channel, ECaC

Eukaryota
Metazoa
ECaC of Oryctolagus cuniculus
*1.A.4.2.4









Insulin-like growth factor I-regulated Ca2+ channel

Eukaryota
Metazoa
IGF-regulated Ca2+ channel of Mus musculus
*1.A.4.2.5









Vanilloid receptor-related, osmotically activated channel, VR-OAC (also called TRPV4 and Trp12); required for bladder voiding in mice (Gevaert et al., 2007). Regulated by Pacsin3 via its SH3 domain which affects its subcellular localization and inhibits its activity in a stimulus-specific fashion (D'hoedt et al., 2008). Responsible for autosomal dominant brachyolmia (Rock et al., 2008). Multiple gating mechanisms have been demonstrated for TRPV4 (Loukin et al., 2010). TRPV4 Ca2+ signalling regulates endothelial vascular function (Sonkusare et al., 2012) and adipose oxidative metabolism, inflammation and energy homeostasis (Ye et al. 2012).  H2O2 induces Ca2+ influx into microvascular endothelial cells via TrpV4 (Suresh et al. 2015). TrpV4 orthologs are volume-sensors, rather than osmo-sensors (Toft-Bertelsen et al. 2017) that mediate fluid secretion by the ciliary body. They are important for vertebrate vision by providing nutritive support to the cornea and lens, and by maintaining intraocular pressure (Jo et al. 2016). Interacts with the A-kinase anchor protein 5 (AKAP5 or AKAP79 of 427 aas; TC# 8.A.28.1.6; P24588) (Mack and Fischer 2017).

Eukaryota
Metazoa
VR-OAC of Rattus norvegicus
*1.A.4.2.6









Osmosensitive transient receptor potential channel 3, O-TRP3
Eukaryota
Metazoa
O-TRP3 of Mus musculus
*1.A.4.2.7









Intestinal endocyte Ca2+ (Sr2+; Ba2+) entry channel, CaT1. Excision of the Trpv6 gene leads to severe defects in epididymal Ca2+ absorption and male fertility as does the single D541A pore mutation (Weissgerber et al., 2012).

Eukaryota
Metazoa
CaT1 of Rattus norvegicus
*1.A.4.2.8









The noxious heat (>52°C)-sensitive vanilloid-like receptor cation selective channel, TRPV2. Ca2+-dependent desensitization of TRPV2 channels is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate (Mercado et al., 2010).  Deleting the first N-terminal 74 residues preceding the ankyrin repeat domain (ARD) shows a key role for this region in targeting the protein to the membrane. Co-translational insertion of the membrane-embedded region occurs with the TM1-TM4 and TM5-TM6 regions assembling as independent folding domains. ARD is not required for TM domain insertion into the membrane (Doñate-Macian et al. 2015).  The TRPV2 structure has been solved at 4 Å resolution by cryoEM (Zubcevic et al. 2016).

Eukaryota
Metazoa
TRPV2 of Homo sapiens
*1.A.4.2.9









The temperature (heat; >39°C)-sensitive, capsaicin-insensitive receptor cation-selective channel, TRPV3 or TRL3 (may form heterooligomers with VR1 (TRPV1; TC #1.A.4.2.1)). Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain (Moussaieff et al., 2008).  TRPV3 is activated by synthetic small-molecule chemicals and natural compounds from plants as well as warm temperatures. Its function is regulated by a variety of physiological factors including extracellular divalent cations and acidic pH, intracellular ATP, membrane voltage, and arachidonic acid. It shows a broad expression pattern in both neuronal and non-neuronal tissues including epidermal keratinocytes, epithelial cells in the gut, endothelial cells in blood vessels, and neurons in dorsal root ganglia and the CNS. TRPV3 null mice exhibit abnormal hair morphogenesis and compromised skin barrier function, and it may play critical roles in inflammatory skin disorders, itch, and pain sensation (Luo and Hu 2014).

Eukaryota
Metazoa
TRPV3 of Homo sapiens
*1.A.4.2.10









TRPV5 epithelial Ca2+ channel (ECaCl) (forms homo- and heterotetrameric channels with TRPV6; requires the S100A10-annexin 2 complex for routing to the plasma membrane) (Hoenderop et al., 2003; van de Graaf et al., 2003).  The kidney maintains whole body calcium homoeostasis due to the reabsorption of Ca2+ filtered by the kidney glomerulus. TRPV5 regulates urinary Ca2+ excretion by mediating active Ca2+ reabsorption in the distal convoluted tubule of the kidney. The histidine kinase, nucleoside diphosphate kinase B (NDPK-B), activates TRPV5 channel activity and Ca2+ flux, and this activation requires histidine 711 in the carboxy terminal tail of TRPV5. In addition, the histidine phosphatase, protein histidine phosphatase 1 (PHPT1), inhibits NDPK-B activated TRPV5 (Cai et al. 2014).  TRPV5 also transports cadmium (Cd2+).

Eukaryota
Metazoa
TRPV5 of Homo sapiens (NP_062815)
*1.A.4.2.11









TRPV6 epithelial Ca2+ channel (ECaC2) (forms homo- and heterotetrameric channels with TRPV5; requires the S100A10-annexin 2 complex for routing to the plasma membrane) (Hoenderop et al., 2003; van de Graaf et al., 2003). Epithelial TrpV6, but not TrpV5, is inhibited by the regulator of G-protein signaling 2 (RGS2; Q9JHX0; 211 aas) by direct binding (Schoeber et al., 2006). Cyclophilin B is an accessory activating protein (Stumpf et al., 2008).  The crystal structure of rat TRPV6 at 3.25 A resolution revealed shared and unique features compared with other TRP channels (Saotome et al. 2016). Intracellular domains engage in extensive interactions to form an intracellular 'skirt' involved in allosteric modulation. In the K+ channel-like transmembrane domain, Ca2+ selectivity is determined by direct coordination of Ca2+ by a ring of aspartate side chains in the selectivity filter (Saotome et al. 2016).  Replacing Gly-516 within the cytosolic S4-S5 linker (conserved in all TRP channel proteins) by ser forces the channels into an open conformation, thereby enhancing constitutive Ca2+ entry and preventing inactivation (Hofmann et al. 2016).

Eukaryota
Metazoa
TRPV6 of Homo sapiens (NP_071858)
*1.A.4.2.12









Epithelial calcium channel, ECaC (Liao et al., 2007).
Eukaryota
Metazoa
ECaC of Danio rerio (Q6JQN0)
*1.A.4.2.13









TrpV1 of 839 aas.  Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia (Benemei et al. 2015).  The 3.4 Å resolution structure shows that the overall fold is the same as for voltage-gated ion channel (TC# 1.A.1) (Liao et al. 2013). Capsaicin-induced apoptosis in Glioma is mediated by TRPV1 (Amantini et al. 2007). Capsaicin binds to a pocket formed by the channel's TMSs, where it takes a "tail-up, head-down" configuration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, capsaicin stabilizes the open state of TRPV1 by "pull-and-contact" with the S4-S5 linker (Yang and Zheng 2017).

Eukaryota
Metazoa
TrpV1 of Homo sapiens
*1.A.4.3.1









Olfactory, mechanosensitive channel. Forms a complex with Stim1 and Orai1 (TC# 1.A.52.1.1) which is required for SOC currents (Cheng et al., 2008) (most similar to 1.A.4.8.1, but both are most closely related to 1.A.4.2).  Serves as a chemo-, osmo- and touch sensation receptor (Xiao and Xu 2009).

Eukaryota
Metazoa
Olfactory channel of Caenorhabditis elegans
*1.A.4.3.2









The Nanchung (Nan) hearing ion channel; mediates hypo-osmotically activated Ca2+ influx in chordotonal neurons of insects (Kim et al., 2003). Nanchung is the "dry" humidity receptor, one of two hygrosensation receptors. These two transient receptor potential channels are needed for sensing humidity.  The other is Water witch (Wtrw), involved in detecting moist air. Neurons associated with specialized sensory hairs in the third segment of the antenna express these channels, and neurons expressing Wtrw and Nan project to central nervous system regions associated with mechanosensation. Construction of the hygrosensing system with opposing receptors may allow an organism to very sensitively detect changes in environmental humidity (Liu et al. 2007).

Eukaryota
Metazoa
Nan of Drosophila melanogaster (833 aas; Q9VUD5)
*1.A.4.3.3









TrpV-type Osm-2 (OSM2) chemo-, osmo- and touch sensation receptor channel (Xiao and Xu 2009).

Eukaryota
Metazoa
Osm-2 of Caenorhabditis elegans
*1.A.4.3.4









TRP channel homologue of 1240 aas

Eukaryota
Phaeophyceae
TRP channel homologue of Ectocarpus siliculosus
*1.A.4.3.5









TRP channel homologue of 1724 aas

Eukaryota
Phaeophyceae
TRP channel homologue of Ectocarpus siliculosus (Brown alga)
*1.A.4.4.1









Vacuolar, voltage-dependent cation-selective, Ca2+-activated channel, YVC1. (Yeast vacuolar conductance protein 1; also called TrpY1; Yor088w) (Chang et al., 2009). Activated by stretch to release vacuolar Ca2+ into the cytoplasm upon osmotic upshock. (Activated by glucose, indole and other aromatic compounds (Haynes et al., 2008; Groppi et al. 2011)).  Glutathione activates by reversible glutathionylation of specific cysteyl residues in YVC1 (Chandel et al. 2016).

Eukaryota
Fungi
YVC1 (Yor088w) of Saccharomyces cerevisiae (Q12324)
*1.A.4.5.1









Mg2+-selective channel/kinase-1; Mg2+-ATP-regulated divalent cation channel, LTRPC7, TRPM7, or TRP-PLIK, of 1862 aas. Bradykinin regulates TRPM7 and its downstream target annexin-1 through a phospholipase C-dependent, protein kinase C-dependent and c-Src-dependent pathway that is cAMP-independent; effects are mediated through the bradykinin type 2 receptor (Callera et al. 2009).  TRPM7 is a Mg2+ sensor and transducer of signaling pathways during stressful environmental conditions. Its kinase can act on its own in chromatin remodeling processes, but TRPM6's kinase activity regulates intracellular trafficking of TRPM7 and TRPM7-dependent cell growth (Cabezas-Bratesco et al. 2015).  Syndecans (proteoglycans) regulate TRPC channels to control cytosolic calcium equilibria and consequent cell behavior. In fibroblasts, ligand interactions with heparan sulfate of syndecan-4 recruit cytoplasmic protein kinase C to target serine714 of TRPC7 with subsequent control of the cytoskeleton and the myofibroblast phenotype (Gopal et al. 2015).  May be associated with melanocytic tumors.  Phenanthrenes, naltriben derivatives, are stimulatory agonist of the TRPM7 channel (Liu et al. 2016).

Eukaryota
Metazoa
Channel-kinase-1 (LTRPC7) of Homo sapiens
*1.A.4.5.2









Melastatin 1 or transient receptor potential melastatin-1 (TRPM1; LTRPC1, MLSN, MLSN1) (a non-selective, Ca2+-permeable cation channel, implicated in cell death (Wilkinson et al., 2008).  Required for dim light vision.  Purified TRPM1 is mostly dimeric. The three-dimensional structure of TRPM1 dimers is characterized by a small putative transmembrane domain and a larger domain with a hollow cavity (Agosto et al. 2014). Since dimers are not likely to be functional ion channels, the authors suggested that additional partner subunits participate in forming the transduction channel required for dim light vision and the ON pathway.  The N-terminal region of TRPM1 (residues L242 to E344) regulates activity by direct interaction by the S100A1 calcium-binding protein (TC# 8.A.81) (Jirku et al. 2016).

Eukaryota
Metazoa
Melastatin 1 of Homo sapiens
*1.A.4.5.3









MLSN1- and TRP-related MTR1 of 1165 aas.  Associated with the Beckman-Wiedemann Syndrum and causes a predisposition for neoplasia (Prawitt et al. 2000).

Eukaryota
Metazoa
MTR1 of Homo sapiens
*1.A.4.5.4









Ca2+-activated nonselective cation (Na+ and K+) channel (non-permeable to Ca2+), TRPM4b. Forms a protein-protein interaction with the TRPC3 channel and suppresses store-operated Ca+ entry (Park et al., 2008).  Contributes to the mammalian atrial action potential (Simard et al. 2013).

Eukaryota
Metazoa
TRPM4b of Homo sapiens
*1.A.4.5.5









ADP-ribose/NAD/pyrimidine nucleotide-gated Ca2+ permeable, cation nonselective, long transient receptor potential channel-2, LTRPC2; Melastatin 2; TRPM2 (ATP inhibitable). The 3-D structure resembles a swollen bell shaped structure (Maruyama et al., 2007). Can be converted to an anion selective channel by introducing a lysyl residue in TMS 6 (Kuhn et al., 2007). Transports Ca2+ and Mg2+ with equal facility (Xia et al., 2008).  Four Ca2+ ions activate TRPM2 channels by binding in deep crevices near the pore but intracellularly of the gate (Csanády and Törocsik, 2009). Protons also regulate activity (Starkus et al., 2010). Present in the plasma membrane and lysosomes; plays a role in ROS-induced inflammatory processes and cell death. Melastatin is required for innate immunity against Listeria monocytogenes (Knowles et al., 2011). Functions in pathogen-evoked phagocyte activation, postischemic neuronal apoptosis, and glucose-evoked insulin secretion, by linking these cellular responses to oxidative stress (Tóth and Csanády, 2012).  Pore collapse upon prolonged stimulation underlies irreversible inactivation (Tóth and Csanády 2012).  TRPM2 is preferentially expressed in cells of the myeloid lineage and modulates signaling pathways converging into NF-kB but does not seem to play a major role in myeloid leukemogenesis. Its loss does not augment the cytotoxicity of standard AML chemotherapeutic agents (Haladyna et al. 2016).  TrpM2, expressed in hypothalamic neurons in the brain is a thermosensitive, redox-sensitive channel, required for thermoregulation.  It regulates body temperature, limiting fever and driving hypothermia (Song et al. 2016). 

Eukaryota
Metazoa
LTRPC2 of Homo sapiens
*1.A.4.5.6









Transient receptor potential cation channel subfamily, member 3. Activated by muscarinic receptor activation.

Eukaryota
Metazoa
TrpM3 of Homo sapiens (Q9HCF6)
*1.A.4.5.7









Cold-sensitive (opens with decreasing temperatures; e.g., <22°C) and menthol-sensitive cation-selective channel, TRPM8. TRPM8 is activated by low temperatures and cooling agents such as menthol. It underlies the cold-induced excitation of sensory neurons. Its gating is regulated by voltage and lysophospholipids which induce prolonged channel opening (Vanden Abeele et al., 2006; Bautista et al., 2007; Matta and Ahern, 2007). Can be converted to an anion-selective channel by introducing a lysyl residue in TMS 6 (Kuhn et al., 2007). Gating of transient receptor potential melastatin 8 (TRPM8) channels is activated by cold and chemical agonists in planar lipid bilayers (Zakharian et al., 2010). Residues involved in intra- and intersubunit interactions have been identified, and their link with the channel activity, sensitivity to icilin, menthol and cold, and impact on channel oligomerization have been measured (Bidaux et al. 2015).  Targeting the small isoform of TrpM8 may be useful to fight prostate cancer (Bidaux et al. 2016).

Eukaryota
Metazoa
TRPM8 of Homo sapiens
*1.A.4.5.8









The intestinal/renal Mg2+ absorption Mg2+ influx channel, Melastatin6 or TRPM6 (5x higher affinity for Mg2+ than Ca2+; regulated by internal Mg2+) (Voets et al., 2004). TRPM6 and its closest homologue TRPM7 (also a Mg2+-permeable cation channel) assemble to form a functional heterooligomeric channel (Chubanov et al., 2004).  Mutations in TRPM6 promotes hypomagnesemia with secondary hypocalcemia (Chubanov et al., 2007). TRPM6 and the closely related TRPM7 are large channel-kinase proteins (Li et al., 2007; Schmitz et al., 2007). TRPM7 also transports protons competitively with Mg2+ and Ca2+ (Numata and Okada, 2008). Intracellular ATP regulates TRPM6 channel activity via its α-kinase domain independently of α-kinase activity (Thébault et al., 2008). Also plays a role in Zn2+ homeostasis and Zn2+- mediated neuronal injury (Inoue et al., 2010).  The protein is cleaved to release a chromatin-modifying kinase (Krapivinsky et al. 2014).  TRPM7 is a Mg2+ sensor and transducer of signaling pathways under stressful environmental conditions. Its kinase can act on its own in chromatin remodeling processes, but TRPM6's kinase activity regulates intracellular trafficking of TRPM7 and TRPM7-dependent cell growth (Cabezas-Bratesco et al. 2015).  Residues involved in cation selectivity have been identified (Topala et al. 2007).

Eukaryota
Metazoa
TRPM6 of Homo sapiens (NP_060132)
TRPM7 of Homo sapiens (TC #1.A.4.5.1)
*1.A.4.5.9









Transient receptor potential cation channel TrpM

Eukaryota
Metazoa
T9.a.14.4.12rpM of Drosophila melanogaster
*1.A.4.5.10









TrpCC family member, Gon2. Required for initiation and continuation of postembryonic mitotic cell division of gonadal cells Z1 and Z4. Zygotic expression is necessary for hermaphrodite fertility. Probably a cation channel that functions together with Gem1 (TC#2.A.1.13.22) (Kemp et al. 2009).
Eukaryota
Metazoa
Gon-2 of Caenorhabditis elegans
*1.A.4.6.1









Cold-activated cation channel in nociceptive sensory neurons, ANKTM1, with lower activation temperature (in the noxious cold range) than TRPM8 (TC #1.A.4.5.7) (Story et al., 2003). Also called TRPA1 (Acc #AAS78661) which translates sound into electric signals in the ear. It sits at the tips of cilia in the inner ear and allows passage of K+ and Ca2+ into the cell. Vibrations in the hair cause the channel to open and close. The frequency of the sound waves generate an electrical signal of the same frequency (Jordt et al., 2004). (Shows 25% identity with α-latrotoxin precursor (TC #1.C.6.3.1.1) in its N-terminal half.) TRPA1 is a polyunsaturated fatty acid sensor in mammals, but not in flies and fish (Motter and Ahern, 2012). TRPA1 is regulated by its N-terminal ankyrin repeat domain (Zayats et al., 2012).

Eukaryota
Metazoa
ANKTM1 of Mus musculus (Q8BLA8)
*1.A.4.6.2









Warm-activated thermosensory cation channel of insects, ANKTM1 or TrpA1 (Viswanath et al., 2003). It is required to control activity during the warm part of the day (Roessingh et al. 2015). The TrpA1(A) transcript spliced with exon10b (TrpA1(A)10b) that is present in a subset of midgut enteroendocrine cells (EECs) is critical for uracil-dependent defecation of microorganisms (Du et al. 2016).

Eukaryota
Metazoa
ANKTM1 of Drosophila melanogaster (1197 aas; Q7Z020)
*1.A.4.6.3









The nociceptive neuron TRPA1 (Trp-ankyrin 1) senses peripheral damage by transmitting pain signals (activated by cold temperatures, pungent compounds and environmental irritants). Noxious compounds also activate through covalent modification of cysteyl residues (Macpherson et al., 2007). TRPA1 is an excitatory, nonselective cation channel implicated in somatosensory function, pain, and neurogenic inflammation. Through covalent modification of cysteine and lysine residues, TRPA1 can be activated by electrophilic compounds, including active ingredients of pungent natural products (e.g., allyl isothiocyanate), environmental irritants (e.g., acrolein), and endogenous ligands (4-hydroxynonenal) (Chen et al., 2008). General anesthetics activate TRPA1 nociceptive ion channels to enhance pain and inflammation (Matta et al., 2008; Leffler et al., 2011). TMS5 is a critical molecular determinant of menthol sensitivity (Xiao et al., 2008). TRPA1 is a component of the nociceptive response to CO2 (Wang et al., 2010). TRPA1 is a polyunsaturated fatty acid sensor in mammals but not in flies and fish (Motter and Ahern, 2012). It  is regulated by its N-terminal ankyrin repeat domain (Zayats et al., 2012).  Mutations in TrpA1 cause alterred pain perception (Kremeyer et al. 2010). The hop compound, eudesmol, an oxygenated sesquiterpene, activates the channel (Ohara et al. 2015).  These channels regulate heat and cold perception, mechanosensitivity, hearing, inflammation, pain, circadian rhythms, chemoreception, and other processes (Laursen et al. 2014).  TRPA1 is a polymodal ion channel sensitive to temperature and chemical stimuli, but its resposes are species specific (Laursen et al. 2015). A probable binding site for general anesthetics has been identified (Ton et al. 2017).

Eukaryota
Metazoa
TRPA1 of Homo sapiens (O75762)
*1.A.4.6.4









The Pyrexia (Pyx) thermal TRP channel allowing increased tolerance to high temperature (Lee et al., 2005)
Eukaryota
Metazoa
Pyx of Drosophila melanogaster (Q9W0T5)
*1.A.4.6.5









Thermosensitive TPR channel TRPA1 (TrpA-1) of 1211 aas.  Detects a temperature drop promoting increased longevity.  This requires TPRA1-mediated Ca2+ influx and activation of protein kinase C.  Human TRPA1 (TC# 1.A.4.6.3) can functionally substitute for worm TRPA-1 in promoting longevity (Xiao et al. 2013).  Also mediates touch sensation.

Eukaryota
Metazoa
TRPA1 of Caenorhabditis elegans
*1.A.4.6.6









Water witch (Wtrw) of 986 aas, the "moist" humidity receptor, one of two hygrosensation receptors. These two transient receptor potential channels are needed for sensing humidity.  The other is Nanchung (Nan), involved in detecting dry air. Neurons associated with specialized sensory hairs in the third segment of the antenna express these channels, and neurons expressing Wtrw and Nan project to central nervous system regions associated with mechanosensation. Construction of the hygrosensing system with opposing receptors may allow an organism to very sensitively detect changes in environmental humidity (Liu et al. 2007).

Eukaryota
Metazoa
WtrW of Drosophila melanogaster
*1.A.4.6.7









TRP ankyrin 1 (TRPA1 of 1188 aas).  It is a homotetrameric, non-selective, cation channel with multiple ankyrin repeats at the N-terminus.  The systems from insects to birds are heat activatable, and this activation is dependent on an extracellular Ca2+ binding site near the vestibule surface. Neutralization of acidic amino acids by extracellular Ca2+ seems to be important for heat-evoked activation (Kurganov et al. 2017).

Eukaryota
Metazoa
TRPA1 of Anolis carolinensis (Green anole) (American chameleon)
*1.A.4.7.1









The mechanically gated hearing and balance ion channel in sensory hair cells of the vertebrate inner ear, NompC (Sidi et al., 2003)
Eukaryota
Metazoa
NompC of Danio rerio (zebrafish) (1614 aas; Q7T1G6)
*1.A.4.7.2









The sensory ion channel in tactile bristles of insects, NompC
Eukaryota
Metazoa
NompC of Drosophila melanogaster (1619 aas; AAF59842)
*1.A.4.7.3









The pore forming subunit, Trp-4, a mechanosensitive cation/Ca2+ channel. Present in ciliated mechanosensitive neurons; Activation and latency occur in the microsecond range. trp-4 mutations alter ion selectivity (Kang et al., 2010; Xiao and Xu 2009). 

Eukaryota
Metazoa
Trp-4 of Caenorhabditis elegans (Q9GRV5)
*1.A.4.9.1









Flavin carrier protein 1 (Bypass of PAM1 protein 1) (FAD transporter 1) (Heme utilization factor 1) (TRP-like ion channel protein FLC1)
Eukaryota
Fungi
FLC1 of Saccharomyces cerevisiae
*1.A.4.9.2









TRP-like ion channel PKD2 (Polycystic kidney disease-related ion channel 2).  Regulates cytoplasmic calcium ion concentrations (Ma et al. 2011).

Eukaryota
Fungi
Pkd2 of Schizosaccharomyces pombe
*1.A.4.9.3









Flavin carrier protein 2, Flc2p. May be responsible for the transport of FAD (and heme) into the endoplasmic reticulum lumen, where FAD may be required for oxidative protein folding involved in disulfide bridge formation (Protchenko et al. 2006).

Eukaryota
Fungi
Flc2 of Saccharomyces cerevisiae
*1.A.4.9.4









Trp-like channel protein

Eukaryota
Fungi
TRP-like channel protein of Schizosaccharomyes pombe (O94543)
*1.A.4.10.1









TRP cation-slective channel homologue of 1177 aas

Eukaryota
Viridiplantae
TRP channel homologue of Chlamydomonas reinhardtii (Chlamydomonas smithii)
*1.A.4.10.2









TRP channel homologue of 962 aas

Eukaryota
Intramacronucleata
TRP channel homologue of Oxytricha trifallax
*1.A.4.10.3









TRP channel homologue of 1486 aas

Eukaryota
Viridiplantae
TRP channel homologue of Volvox carteri