TRPM8
Domain
The coiled coil region is required for multimerization.
Cooling agents bind within a pocket formed entirely by the S1-S4 helices that opens to the cytoplasm.
Function
Non-selective ion channel permeable to monovalent and divalent cations, including Na(+), K(+), and Ca(2+), with higher permeability for Ca(2+). Activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality. Activated by cool temperatures (<23-28 degrees Celsius) and by chemical ligands evoking a sensation of coolness, such as menthol and icilin therefore plays a central role in the detection of environmental cold temperatures (PubMed:15306801, PubMed:15852009, PubMed:16174775, PubMed:25559186, PubMed:37857704). TRPM8 is a voltage-dependent channel; its activation by cold or chemical ligands shifts its voltage thresholds towards physiological membrane potentials, leading to the opening of the channel (PubMed:15306801). In addition to its critical role in temperature sensing, regulates basal tear secretion by sensing evaporation-induced cooling and changes in osmolality (By similarity). May plays a role in prostate cancer cell migration (PubMed:16174775, PubMed:25559186).
Isoform 2
Negatively regulates menthol- and cold-induced channel activity by stabilizing the closed state of the channel.
Isoform 3
Negatively regulates menthol- and cold-induced channel activity by stabilizing the closed state of the channel.
Sequence Similarities
Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM8 sub-subfamily.
Tissue Specificity
Expressed in prostate. Also expressed in prostate tumors and in non-prostatic primary tumors such as colon, lung, breast and skin tumors.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Membrane raft
- Endoplasmic reticulum membrane
- Lipid raft association modulates TRPM8 channel activity (By similarity). Located in the endoplasmic reticulum in prostate cancer cells (PubMed:11325849, PubMed:16174775).
Alternative names
LTRPC6, TRPP8, TRPM8, Transient receptor potential cation channel subfamily M member 8, Long transient receptor potential channel 6, Transient receptor potential p8, LTrpC-6, LTrpC6, Trp-p8