TMEM110 , also designated as STIMATE (representing STIM-activating enhancer), is an ER-resident multi-transmembrane protein discovered through a proteomic study on the ER-PM junctions, a specialized junctional sites that connect the plasma membrane (PM) and endoplasmic reticulum (ER) to play critical roles in controlling lipid metabolism and calcium signaling. TMEM110/ STIMATE functions as a positive modulate of calcium influx mediated by STIM-ORAI signaling in vertebrates. STIMATE has been demonstrated to physically interact with STIM1 to promote STIM1 conformational switch. Genetic depletion of STIMATE substantially reduces STIM1 puncta formation at ER-PM junctions and suppresses the calcium/calcineurin/NFAT signaling axis. Further genetic studies are required to fully elucidate the function of STIMATE in normal physiology and disease, and to uncover more uncharted functions of this recently discovered molecules at ER-PM junctions. [1]
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