synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 domain-containing protein 2-like (C2CD2L) and similar proteins
This family includes C2 domain-containing protein 2 (C2CD2) and C2CD2-like (C2CD2L). C2CD2 (also called transmembrane protein 24-like or TMEM24L), may be a lipid-binding protein that shows high sequence similarity with C2 domain-containing protein 2-like (C2CD2L; also called transmembrane protein 24 or TMEM24). C2CD2L is a 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 (ER) to the cell membrane. It is a Ca2+-regulated component of ER-plasma membrane contacts in mammalian neurons. This model corresponds to the SMP domain of C2CD2 and C2CD2L which binds glycerolipids with a preference for phosphatidylinositol (PI). The bound PI is then transferred to the plasma membrane (PM) where it is converted to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to replenish pools of this lipid hydrolyzed during glucose-stimulated signaling. PI(4,5)P2 is required for Ca2+-dependent exocytosis; hence, the SMP domain of TMEM24 is essential for sustaining the intracellular Ca2+ oscillations that trigger bursts of insulin granule release and subsequent insulin secretion.
Jiyao W et al.(2023). "The conserved domain database in 2023.",