GRAM domain-containing 2A protein (GRAMD2A; formerly GRAMD2) is a protein encoded by the GRAMD2A gene.[1] Like GRAMD2B, the protein consists of a GRAM domain and a transmembrane domain that anchors it to the endoplasmic reticulum.[2] [3]
GRAMD2A is a mammalian representative of the yeast lipid transfer proteins anchored at a membrane contact site (LAM) family.[3] It has four paralogs: GRAMD1A, GRAMD1B, GRAMD1C and GRAMD2B. Unlike LAM and its paralogs except GRAMD2B, GRAMD2A lacks a VASt domain.
The protein localizes to sites where membranes from different organelles are in close apposition.[3] There, it tethers the endoplasmic reticulum to the plasma membrane through its GRAM domain binding phosphatidylinositol 4,5-bisphosphate in the plasma membrane at sites enriched for the phospholipid.[3] The protein ensures proper stromal interaction molecule 1 (STIM1) recruitment to these sites of membrane contact as part of the store-operated calcium entry pathway – a component of intracellular calcium homeostasis.[3]