Domains of STIM proteins. Drosophila and human STIM proteins are situated in the ER membrane. Modules of STIM1, STIM2 and Stim include: the signal peptide, the predicted EF-hand and SAM domains, the transmembrane region and two regions predicted to form coiled-coil structures comprising the ERM domain. Proline-rich domains (P) and the lysine-rich C-terminal regions are unique to the mammalian STIM family members. Drosophila Stim contains an N-terminal sequence in the ER that is not present in either STIM1 or STIM2. The N-linked glycosylation sites at the SAM domain, experimentally verified for STIM1 (refs , ), are also indicated. Background colours represent basal Ca2+ concentrations of ~50 nM in the cytosol and > 400 µM in the ER lumen. Ca2+ ions are shown as red dots, including Ca2+ bound to the EF-hand domain.