C2CD2L
Domain
The SMP-LBD domain is a lipid transport module, which binds glycerolipids with a preference for phosphatidylinositol (PI).
Function
Lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane (PubMed:28209843). It thereby maintains the pool of cell membrane phosphoinositides, which are degraded during phospholipase C (PLC) signaling (PubMed:28209843). Plays a key role in the coordination of Ca(2+) and phosphoinositide signaling: localizes to sites of contact between the endoplasmic reticulum and the cell membrane, where it tethers the two bilayers (PubMed:28209843). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C-terminus and dissociates from the cell membrane, abolishing phosphatidylinositol transport to the cell membrane (PubMed:28209843). Positively regulates insulin secretion in response to glucose: phosphatidylinositol transfer to the cell membrane allows replenishment of PI(4,5)P2 pools and calcium channel opening, priming a new population of insulin granules (PubMed:28209843).
Post-translational modifications
Phosphorylation at the C-terminus acidifies the protein and leads to disassociation from the acidic cell membrane. Reassociates with the cell membrane upon dephosphorylation.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass membrane protein
- Cell membrane
- Peripheral membrane protein
- Localizes to sites of contact between the endoplasmic reticulum and the cell membrane (PubMed:28209843). Embedded into the endoplasmic reticulum membrane via its N-terminal transmembrane domain and associates with cell membrane via its C-terminus (PubMed:28209843). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C-terminus and dissociates from the cell membrane and localizes to the reticular endoplasmic reticulum (PubMed:28209843). Reassociates with cell membrane upon dephosphorylation (PubMed:28209843).
Alternative names
KIAA0285, TMEM24, DLNB23, C2CD2L, Phospholipid transfer protein C2CD2L, C2 domain-containing protein 2-like, Transmembrane protein 24, C2CD2-like