Protein: Transient receptor potential cation channel subfamily M member 8 (Long transient receptor potential channel 6) (LTrpC-6) (LTrpC6) (Transient receptor potential p8) (Trp-p8) (Q7Z2W7)
Organism: Homo sapiens (Human)
Function: Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable 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 agonist 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. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity. Plays a role in prostate cancer cell migration. Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel.
Subcellular location: Cell membrane {ECO:0000269|PubMed:16174775}; Multi-pass membrane protein {ECO:0000269|PubMed:37857704}. Membrane raft {ECO:0000250|UniProtKB:Q8R4D5}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:11325849, ECO:0000269|PubMed:16174775}. Note=Lipid raft association modulates TRPM8 channel activity (By similarity). Located in the endoplasmic reticulum in prostate cancer cells (PubMed:11325849, PubMed:16174775). {ECO:0000250|UniProtKB:Q8R4D5, ECO:0000269|PubMed:11325849, ECO:0000269|PubMed:16174775}.
Interaction partners:
- Transient receptor potential cation channel subfamily V member 1
- Transient receptor potential cation channel subfamily A member 1
- Transient receptor potential cation channel subfamily V member 3
- Transient receptor potential cation channel subfamily V member 2
- ADP-ribose pyrophosphatase, mitochondrial
- Serine/threonine-protein phosphatase PP1-gamma catalytic subunit
- Serine/threonine-protein phosphatase PP1-beta catalytic subunit
- Serine/threonine-protein phosphatase PP1-alpha catalytic subunit
- Transient receptor potential cation channel subfamily V member 4
- Ankyrin-1
Sequence:
MSFRAARLSMRNRRNDTLDSTRTLYSSASRSTDLSYSESDLVNFIQANFKKRECVFFTKDSKATENVCKCGYAQSQHMEGTQINQSEKWNYKKHTKEFPTDAFGDIQFETLGKKGKYIRLSCDTDAEILYELLTQHWHLKTPNLVISVTGGAKNFALKPRMRKIFSRLIYIAQSKGAWILTGGTHYGLMKYIGEVVRDNTISRSSEENIVAIGIAAWGMVSNRDTLIRNCDAEGYFLAQYLMDDFTRDPLYILDNNHTHLLLVDNGCHGHPTVEAKLRNQLEKYISERTIQDSNYGGKIPIVCFAQGGGKETLKAINTSIKNKIPCVVVEGSGQIADVIASLVEVEDALTSSAVKEKLVRFLPRTVSRLPEEETESWIKWLKEILECSHLLTVIKMEEAGDEIVSNAISYALYKAFSTSEQDKDNWNGQLKLLLEWNQLDLANDEIFTNDRRWESADLQEVMFTALIKDRPKFVRLFLENGLNLRKFLTHDVLTELFSNHFSTLVYRNLQIAKNSYNDALLTFVWKLVANFRRGFRKEDRNGRDEMDIELHDVSPITRHPLQALFIWAILQNKKELSKVIWEQTRGCTLAALGASKLLKTLAKVKNDINAAGESEELANEYETRAVELFTECYSSDEDLAEQLLVYSCEAWGGSNCLELAVEATDQHFIAQPGVQNFLSKQWYGEISRDTKNWKIILCLFIIPLVGCGFVSFRKKPVDKHKKLLWYYVAFFTSPFVVFSWNVVFYIAFLLLFAYVLLMDFHSVPHPPELVLYSLVFVLFCDEVRQWYVNGVNYFTDLWNVMDTLGLFYFIAGIVFRLHSSNKSSLYSGRVIFCLDYIIFTLRLIHIFTVSRNLGPKIIMLQRMLIDVFFFLFLFAVWMVAFGVARQGILRQNEQRWRWIFRSVIYEPYLAMFGQVPSDVDGTTYDFAHCTFTGNESKPLCVELDEHNLPRFPEWITIPLVCIYMLSTNILLVNLLVAMFGYTVGTVQENNDQVWKFQRYFLVQEYCSRLNIPFPFIVFAYFYMVVKKCFKCCCKEKNMESSVCCFKNEDNETLAWEGVMKENYLVKINTKANDTSEEMRHRFRQLDTKLNDLKGLLKEIANKIK