Figure 1.

STIM1 and SOC activation. In this example, cell activation begins with an agonist binding to a surface membrane receptor (R), coupled to PLC through a G-protein (G) mechanism. PLC activation leads to the production of IP₃, which in turn activates the IP₃ receptor (IP₃R) causing release of Ca²⁺ from a critical compartment of the ER. The fall in ER Ca²⁺ then signals to plasma membrane store-operated channels (SOC) through a mechanism that involves STIM1 in the ER, plasma membrane, or both. The structure of STIM1 includes an EF hand and SAM domain NH₂-terminal to a single transmembrane (TM) domain; these domains would face the lumen of the ER and extracellular space, and the EF hand in particular may be involved in sensing ER Ca²⁺ levels, or in Ca²⁺ regulation at the plasma membrane. COOH-terminal to the TM domain are two coiled-coil (CC) domains, and a serine/proline-rich (S/P Rich) and lysine (K Rich) domain. The EF hand domain is shown in red on the signaling diagram as well as the domain map to indicate the presumed orientation of the protein across ER and plasma membranes.