motifs/domains
| a large N terminal hydrophilic domain with eight potential N-linked glycosylation sites, and 30 amino acid signal peptide followed by a 29 AA TIP39 precursor-related peptide |
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seven C terminal transmembrane alpha helices |
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an Arg-Arg processing site, and the actual 39 AA TIP39 sequence |
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a N-x-x-D motif playing specific roles in TRPM8 and TRPM2, reflecting different requirements for voltage-dependent and voltage-independent channel gating |
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region adjacent to the C-end of the inner gate in TRPM8 channels plays a central role in allosteric channel activation |
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C terminus of TRPM8 is known to be regulated by PIP2, which is essential for TRPM8 activity |
basic 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 |
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involved in menthol sensation |
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cold- and menthol-sensing ion channel that converts thermal and chemical stimuli into neuronal signals and sensations of cooling/cold |
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may play multiple functional roles, likely to be in a tissue- and activation state-dependent manner |
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TRPM8 channels may also contribute to human cutaneous vasculature control, likely with the involvement of additional neuronal mechanisms |
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presence of TRPM8 in sperm, and this channel could be involved in cell signaling events such as thermotaxis or chemotaxis |
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in epidermal keratinocytes plays a role in epidermal permeability barrier homoeostasis and epidermal proliferation after barrier insult |
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might work as cold and l-menthol receptors on tongue |
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major sensor of environmental cold temperatures |
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gated by cold and its chemical agonists directly, and dependence of its gating on PIP4K2A is a result of direct specific interactions with the lipid |
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major cold receptor in the body, but is found in other tissues, including the testis and on the tail and head of spermatozoa |
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acts as a non-painful cooling sensor |
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functions as a cold receptor in sensory neurons |
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could play a modulatory role in cold thermoreceptor activity |
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post-translational modification of TRPM8 is an important mechanism modulating cold thermoreceptor function, explaining the marked differences in temperature sensitivity observed between recombinant and native TRPM8 ion channels |
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N-glycosylation of TRPM8 has an important role in the intrinsic activity of native TRPM8 channels, could play an important modulatory role in sensory neurons, contributing to the setting of the temperature sensitivity of cold thermoreceptor terminals |
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TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain |
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white adipocytes express the cold receptor TRPM8 which activation induces their "browning" supporting a possible role of this receptor in the control of adipose tissue metabolism and body energy balance |
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TRPV1, TRPA1, and TRPM8 are important to start up a systemic response of energy expenditure, energy allocation, and water retention |
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is gated by physiologically relevant cold temperatures and chemical ligands that induce cold sensations, such as the analgesic compound menthol |
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initiated the cold-shock response by differentially modulating cold- and heat-shock proteins |
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