ORAI1
Calcium release-activated calcium channel protein 1 is a calcium selective ion channel that in humans is encoded by the ORAI1 gene. Orai channels play an important role in the activation of T-lymphocytes. The loss of function mutation of Orai1 causes severe combined immunodeficiency (SCID) in humans The mammalian orai family has two additional homologs, Orai2 and Orai3. Orai proteins share no homology with any other ion channel family of any other known proteins. They have 4 transmembrane domains and form hexamers. Structure and function Orai channels are activated upon the depletion of internal calcium stores, which is called the "store-operated" or the "capacitative" mechanism. They are molecular constituents of the "calcium release activated calcium currents" (ICRAC). Upon activation of phospholipase C by various cell surface receptors, inositol trisphosphate is formed that releases calcium from the endoplasmic reticulum. The decreased calcium concentration in the endoplasmic reticulum is sensed by the STIM1 protein. STIM1 clusters upon the depletion of the calcium stores and forms "puncta", and relocates near the plasma membrane, where it activates Orai1 via protein-protein interaction. In 2012, a 3.35-angstrom (Å) crystal structure of the Drosophila Orai channel, which shares 73% sequence identity with human Orai1 within its transmembrane region,