Two pore channel protein 2

UniProtKB accession:  Q8NHX9

Grouped By:  Matching UniProtKB accession

UniProtKB description:  Intracellular channel initially characterized as a non-selective Ca(2+)-permeable channel activated by NAADP (nicotinic acid adenine dinucleotide phosphate), it is also a highly-selective Na(+) channel activated directly by PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) (PubMed:19387438, PubMed:19620632, PubMed:20880839, PubMed:30860481, PubMed:32167471, PubMed:31825310, PubMed:23063126, PubMed:24776928, PubMed:23394946, PubMed:24502975). Localizes to the lysosomal and late endosome membranes where it regulates organellar membrane excitability, membrane trafficking, and pH homeostasis. Is associated with a plethora of physiological processes, including mTOR-dependent nutrient sensing, skin pigmentation and autophagy (PubMed:32167471, PubMed:23394946, PubMed:18488028). Ion selectivity is not fixed but rather agonist-dependent and under defined ionic conditions, can be readily activated by both NAADP and PI(3,5)P2 (PubMed:31825310, PubMed:32167471, PubMed:24502975). As calcium channel, it increases the pH in the lysosomal lumen, as sodium channel, it promotes lysosomal exocytosis (PubMed:31825310, PubMed:32167471). Plays a crucial role in endolysosomal trafficking in the endolysosomal degradation pathway and is potentially involved in the homeostatic control of many macromolecules and cell metabolites (By similarity) (PubMed:18488028, PubMed:19387438, PubMed:19620632, PubMed:20880839, PubMed:23063126, PubMed:23394946, PubMed:24502975, PubMed:24776928, PubMed:31825310, PubMed:32167471, PubMed:32679067). Also expressed in melanosomes of pigmented cells where mediates a Ca(2+) channel and/or PI(3,5)P2-activated melanosomal Na(+) channel to acidify pH and inhibit tyrosinase activity required for melanogenesis and pigmentation (PubMed:27140606). Unlike the voltage-dependent TPCN1, TPCN2 is voltage independent and can be activated solely by PI(3,5)P2 binding. In contrast, PI(4,5)P2, PI(3,4)P2, PI(3)P and PI(5)P have no obvious effect on channel activation (PubMed:30860481).