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STIM1 Orai1-activating region STIM1 (stromal interaction module 1) is a metazoan transmembrane protein located in the endoplasmic reticulum (ER) membrane, which functions as a sensor for ER calcium ion levels and activates store-operated Ca2+ influx channels (SOCs), such as the Orai1 Ca2+ channel located in the plasma membrane. STIM1 has an N-terminal Ca-binding EF-hand domain, which is located in the ER lumen. Responding to the release of Ca2+ from the ER, STIM1 was found to aggregate near the plasma membrane and contact Orai1. This model describes a region near the C-terminus of STIM1, which has been shown to mediate the interaction with Orai1 and has been labeled SOAR (STIM1 Orai1-activating region). STIM1 has also been linked to sensing oxidative and temperature-variation stress and may play a rather general role in mediating calcium signaling in response to stress. Dimerization of STIM1 via the SOAR domain appears required for the activation of the Orai1 calcium channel. A model for STIM1 activation has been proposed, in which an inhibitory helix N-terminal to the SOAR domain prevents STIM1 clustering or aggregation, and in which conformational changes triggered by depletion of the calcium stores allow the clustering and activation of Orai1. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",