FEATURES

FAMILY

calcium channel alpha-1 subunit (TC 1.A.1.11) family

DESCRIPTION

Also known as TPC2_HUMAN, TPCN2, TPC2. 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) (Probable). 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). 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)., (Microbial infection) During Ebola virus (EBOV) infection, controls the movement of endosomes containing virus particles and is required by EBOV to escape from the endosomal network into the cell cytoplasm., (Microbial infection) Required for cell entry of coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus EMC (HCoV-EMC), by endocytosis. Homodimer (PubMed:30860481). Interacts with LRRK2 (PubMed:22012985). Interacts with HAX1 (PubMed:24188827). Interacts with MTOR; the interaction is required for TPCN2 ATP sensitivity (PubMed:23394946).

EXTERNAL LINKS

TPCN2

Two pore channel protein 2

TPCN2

Molecular Synopsis