This superfamily includes Drosophila Orai and human Orai1, Orai2 and Orai3. Orai is a plasma membrane protein which forms the pore of the CRAC channel (calcium release-activated calcium channel) and generates sustained cytosolic calcium signals when triggered by depletion of calcium from the endoplasmic reticulum. Six Orai subunits assemble around a central ion pore to form a hexameric channel. The pore traverses the membrane and extends 20 angstroms into the cytosol. A ring of glutamates on its extracellular side forms the selectivity filter and a basic region near the intracellular side is able to bind anions that may stabilize the closed state. The architecture of this channel greatly differs from other ion channels, giving insight into the way selective calcium permeation and gating is achieved PMID:23180775.