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Receptor Name
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Transient receptor potential cation channel subfamily M member 4
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Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:29211723). While it is activated by increase in intracellular Ca2+, it is impermeable to it (PubMed:12015988). Mediates 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 Ca2+ 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 Ca2+ 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.
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Gating is voltage-dependent and repressed by decavanadate (PubMed:15331675, PubMed:29211723). Calmodulin-binding confers the Ca2+ sensitivity (PubMed:15590641). ATP is able to restore Ca2+ sensitivity after desensitization (PubMed:15590641). ATP inhibits channel activity (PubMed:15331675, PubMed:14758478, PubMed:29211723). Phosphatidylinositol 4,5-bisphosphate (PIP2)-binding strongly enhances activity, by increasing the channel's Ca2+ sensitivity and shifting its voltage dependence of activation towards negative potentials (PubMed:16186107, PubMed:16424899). Activity is also enhanced by 3,5-bis(trifluoromethyl)pyrazole derivative (BTP2) (PubMed:16407466).
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