Transient receptor potential cation channel subfamily

ts, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)- tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system. Belongs to the transient receptor (TC 1.A.4) family.

Protein type: Membrane protein, integral; Membrane protein, multi-pass

Cellular Component: apical plasma membrane; axon; integral to membrane; integral to plasma membrane; stereocilium bundle

Molecular Function: calcium channel activity; calcium-release channel activity; channel activity; ion channel activity; protein binding; voltage-gated calcium channel activity

Biological Process: calcium ion transport; cell surface receptor linked signal transduction; detection of chemical stimulus involved in sensory perception of pain; detection of mechanical stimulus involved in sensory perception of pain; protein homotetramerization; response to cold; response to drug; response to hydrogen peroxide; response to organic cyclic substance; response to organic substance; response to pain; sensory perception of pain; signal transduction; thermoception; urinary bladder smooth muscle contraction

osomal Location of Human Ortholog: 15q13.3

Cellular Component: integral to plasma membrane; plasma membrane

Molecular Function: calcium channel activity

Biological Process: metabotropic glutamate receptor signaling pathway; transport; visual perception

Disease: Night Blindness, Congenital Stationary, Type 1c

butes to Ca2+ release from intracellular stores in response to ADP-ribose (PubMed:19454650). Plays a role in numerous processes that involve signaling via intracellular Ca2+ levels (Probable). Besides, mediates the release of lysosomal Zn2+ stores in response to reactive oxygen species, leading to increased cytosolic Zn2+ levels (PubMed:25562606). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Activated by intracellular ADP-ribose, beta-NAD (NAD+) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:16260005, PubMed:16601673, PubMed:25562606). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate. Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca2+ levels (PubMed:16601673). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca2+ levels (). Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its function in increasing cytoplasmic Ca2+ and Zn2+ levels (). Confers susceptibility to cell death following oxidative stress (PubMed:16651700, PubMed:11804595, PubMed:19454650, PubMed:25562606).

e been described.

Protein type: Channel, cation; Membrane protein, integral; Membrane protein, multi-pass

Chromosomal Location of Human Ortholog: 9q21.12

Cellular Component: plasma membrane

Molecular Function: calcium channel activity; cation channel activity

Biological Process: cation transport

of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway. Defects in TRPM4 are the cause of progressive familial heart block type 1B (PFHB1B). It is a cardiac bundle branch disorder characterized by progressive alteration of cardiac conduction through the His-Purkinje system, with a pattern of a right bundle-branch block and/or left anterior hemiblock occurring individually or together. It leads to complete atrioventricular block causing syncope and sudden death. Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM4 sub-subfamily. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: Membrane protein, integral; Membrane protein, multi-pass

Cellular Component: cell soma; cytosol; endoplasmic reticulum; Golgi apparatus; integral to membrane; nucleoplasm; plasma membrane

Molecular Function: calcium activated cation channel activity; calcium channel activity; voltage-gated ion channel activity

Biological Process: calcium ion transport; dendritic cell chemotaxis; elevation of cytosolic calcium ion concentration; negative regulation of bone mineralization; negative regulation of osteoblast differentiation; positive regulation of cell proliferation; positive regulation of fat cell differentiation; positive regulation of heart rate; positive regulation of vasoconstriction; protein sumoylation; regulation of membrane potential; regulation of T cell cytokine production

displays rapid activation and deactivation kinetics upon channel stimulation even during sustained elevations in Ca(2+). Also activated by a fast intracellular Ca(2+) increase in response to inositol 1,4,5- triphosphate-producing receptor agonists. The channel is blocked by extracellular acidification. External acidification has 2 effects, a fast reversible block of the current and a slower irreversible enhancement of current inactivation. Is a highly temperature-sensitive, heat activated channel showing a steep increase of inward currents at temperatures between 15 and 35 degrees Celsius. Heat activation is due to a shift of the voltage- dependent activation curve to negative potentials. Activated by arachidonic acid in vitro. May be involved in perception of bitter, sweet and umami tastes. May also be involved in sensing semiochemicals. Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM5 sub-subfamily. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: Membrane protein, integral; Membrane protein, multi-pass

Cellular Component: cell soma; dendrite; integral to membrane

Molecular Function: calcium activated cation channel activity; potassium channel activity; sodium channel activity

the active magnesium absorption in the gut and kidney. ChaK2 mutations cause hereditary hypomagnesemia and secondary hypocalcemia (HSH). The TRP voltage-independent calcium-permeable cation channels are divided into six subfa milies, two of which (TRPC and TRPM) have members that are widely expressed and activated by oxidative stress. Related to ChaK1, another Atypical alpha kinase fused to a TRP ion channel protein. Forms homodimers or heterodimers with ChaK1. Six alternatively spliced isoforms have been described, three of which lack the ion channel region.

Protein type: ATYPICAL group; Alpha family; ChaK subfamily; Channel, cation; EC 2.7.11.1; Kinase, protein; Membrane protein, integral; Membrane protein, multi-pass; Protein kinase, atypical

Cellular Component: apical plasma membrane; brush border membrane

Molecular Function: cation channel activity

Biological Process: metal ion transport; response to toxin

here it binds chromatin-remodeling complexes including Polycomb, and phosphorylates specific histone residues. The kinase activity is essential for the channel function, and channel function is critical to maintain physiological intracellular magnesium levels. Plays a key role in oxidative stress-induced cell death. TRP voltage-independent calcium-permeable cation channels are divided into six subfamilies, two of which (TRPC and TRPM) have members that are widely expressed and activated by oxidative stress. Is activated by reactive oxygen/nitrogen species, resulting in cation conductance and anoxic neuronal cell death. This phenotype is rescued by suppression of ChaK1 expression. Related to ChaK2, another Atypical alpha kinase fused to a TRP ion channel protein.

Protein type: ATYPICAL group; Alpha family; ChaK subfamily; Channel, cation; EC 2.7.11.1; Kinase, protein; Membrane protein, integral; Membrane protein, multi-pass; Protein kinase, atypical

Chromosomal Location of Human Ortholog: 15q21

Cellular Component: plasma membrane

Molecular Function: calcium channel activity

Disease: Amyotrophic Lateral Sclerosis-parkinsonism/dementia Complex 1

meable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonists menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM8 sub-subfamily. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: Channel, cation; Membrane protein, integral; Membrane protein, multi-pass

Cellular Component: external side of plasma membrane; membrane; plasma membrane

Molecular Function: calcium channel activity; ion channel activity; protein homodimerization activity

Biological Process: calcium ion transport; cellular calcium ion homeostasis; protein homotetramerization; response to cold; response to temperature stimulus; thermoception

s as a transducer of painful thermal stimuli in vivo.

Protein type: Channel, cation; Membrane protein, integral; Membrane protein, multi-pass; Receptor, misc.

Chromosomal Location of Human Ortholog: 17p13.2

Cellular Component: integral to membrane; integral to plasma membrane; intrinsic to plasma membrane; plasma membrane; postsynaptic membrane

Molecular Function: ATP binding; calcium channel activity; calcium-release channel activity; excitatory extracellular ligand-gated ion channel activity; extracellular ligand-gated ion channel activity; phosphoinositide binding; phosphoprotein binding; transmembrane receptor activity

Biological Process: cell surface receptor linked signal transduction; chemosensory behavior; protein homotetramerization; thermoception; transport

vated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV2 sub-subfamily.

Protein type: Channel, cation; Membrane protein, integral; Membrane protein, multi-pass

Cellular Component: axon; cell surface; cytoplasm; endomembrane system; integral to plasma membrane; intracellular; lamellipodium; plasma membrane

Molecular Function: calcium channel activity; cation channel activity

Biological Process: apoptosis; negative regulation of cell proliferation; positive regulation of axon extension; response to heat; response to temperature stimulus

ts activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen). May form a heteromeric channel with TRPV1. Interacts with TRPV1. Abundantly expressed in CNS. Widely expressed at low levels. Detected in dorsal root ganglion. Expressed in the keratinocyte layers of the outer root sheath and, to lesser extent, to the matrix of the hair follicles. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV3 sub-subfamily. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: Channel, cation; Membrane protein, integral; Membrane protein, multi-pass

Cellular Component: integral to plasma membrane; membrane; receptor complex

Molecular Function: calcium channel activity; cation channel activity; ion channel activity

Biological Process: negative regulation of hair cycle; response to temperature stimulus

ease of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers. Acts as a regulator of intracellular Ca(2+) in synoviocytes. Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV4 sub-subfamily. 6 isoforms of the human protein are produced by alternative splicing.

Protein type: Channel, cation; Membrane protein, integral; Membrane protein, multi-pass

Cellular Component: adherens junction; cell surface; cilium; cortical actin cytoskeleton; cytoplasmic microtubule; cytoplasmic vesicle; filopodium; focal adhesion; growth cone; integral to plasma membrane; lamellipodium; plasma membrane

Molecular Function: actin binding; actin filament binding; alpha-tubulin binding; beta-tubulin binding; calcium channel activity; calmodulin binding; cation channel activity; microtubule binding; osmosensor activity; protein binding; protein kinase binding; protein kinase C binding; SH2 domain binding; stretch-activated, cation-selective, calcium channel activity

Biological Process: actin cytoskeleton reorganization; actin filament organization; calcium ion transport; cellular calcium ion homeostasis; cortical microtubule organization and biogenesis; diet induced thermogenesis; elevation of cytosolic calcium ion concentration; glucose homeostasis; hyperosmotic salinity response; hypotonic response; intercellular junction assembly; microtubule polymerization; multicellular organismal water homeostasis; negative regulation of transcription from RNA polymerase II promoter; osmosensory signaling pathway; positive regulation of inflammatory response; positive regulation of JNK cascade; positive regulation of microtubule depolymerization; positive regulation of vascular permeability; regulation of response to osmotic stress; response to insulin stimulus; response to lipopolysaccharide; response to osmotic stress; vasopressin secretion

d the current exhibits an inward rectification. A Ca(2+)- dependent feedback regulation includes fast channel inactivation and slow current decay. Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV5 sub-subfamily.

Protein type: Channel, cation; Membrane protein, integral; Membrane protein, multi-pass; Motility/polarity/chemotaxis

Chromosomal Location of Human Ortholog: 7q35

Cellular Component: integral to plasma membrane; plasma membrane

Molecular Function: calcium channel activity; protein binding

Biological Process: calcium ion homeostasis; calcium ion transport; protein tetramerization

um store depletion, and the current exhibits an inward rectification. Inactivation includes both, a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin- dependent mechanism, the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV6 sub-subfamily. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Channel, calcium; Membrane protein, integral; Membrane protein, multi-pass

Cellular Component: apical plasma membrane; integral to plasma membrane; plasma membrane

Molecular Function: calcium activated cation channel activity; calcium channel activity; calmodulin binding

Biological Process: calcium ion homeostasis; calcium ion transport; protein homotetramerization; response to calcium ion