A single lysine in the N-terminal region of store-operated channels

Stromal interaction molecules (STIMs) STIM1 and STIM2 in the ER function as luminal Ca sensors that activate the calcium release–activated calcium (CRAC) channels CRACM1/2/3 (Orai1/2/3) in the plasma membrane after store depletion and give rise to the store-operated CRAC current (ICRAC) (Liou et al., 2005; Roos et al., 2005; Zhang et al., 2005; Feske et al., 2006; Spassova et al., 2006; Vig et al., 2006b; Lis et al., 2007; Parvez et al., 2008). Only the combined overexpression of sensor and channel proteins reconstitutes amplified CRAC currents (Mercer et al., 2006; Peinelt et al., 2006; Soboloff et al., 2006; Zhang et al., 2006; Parvez et al., 2008). All three mammalian CRAC channel homologues (CRACM1, CRACM2, and CRACM3) represent functional store-operated channels, but with distinct characteristics (Lis et al., 2007). STIM1 functions as a Ca sensor in the ER (Liou et al., 2005; Roos et al., 2005; Zhang et al., 2005), and store depletion causes it to redistribute from a diffuse localization throughout