Novel findings suggest the existence of a complex comprised of Orai1, STIM1 and additional proteins. One of these proteins is an EF-hand protein named CRACR2A which regulates Orai-STIM interaction. An EF-hand is a structural domain found in Ca2+ binding proteins consisting of two alpha helices linked by a short loop region.nCRACR2A interacts with the cytoplasmic regions of both Orai1 and STIM1 thus creating a tertiary complex. Under high concentrations of Ca2+, CRACR2A causes a dissociation of Orai1 and STIM1 and a mutated CRACR2A was found, in one study, to cause elevated Ca2+ levels that caused cell death in T cells.nFurther research is required to fully determine the activation and regulation mechanisms of CRACs and this can be performed by better understanding CRACR2A and its binding proteins.
