Stromal interaction molecule (STIM) (STIM)

Stromal interaction molecule (STIM) proteins, primarily STIM1 and STIM2, are essential endoplasmic reticulum (ER)-resident calcium sensors that regulate store-operated calcium entry (SOCE) [1, 10]. Upon depletion of ER calcium stores, STIM proteins undergo a conformational change and oligomerize, translocating to ER-plasma membrane junctions where they bind and activate Orai1 calcium channels [7, 13]. This interaction facilitates the influx of extracellular calcium, which is critical for refilling intracellular stores and activating downstream signaling pathways such as the NFAT transcription factor family [1, 5]. STIM proteins are vital for diverse physiological processes, including immune cell activation, muscle contraction, and gene expression [1, 11]. Dysregulation of STIM-mediated signaling is implicated in a wide range of diseases, including severe combined immunodeficiency, Stormorken syndrome, and various cancers where STIM1 overexpression promotes tumor cell migration and proliferation [5, 9, 15]. Consequently, STIM proteins have emerged as significant therapeutic targets, with small-molecule inhibitors being developed to treat inflammatory conditions, autoimmune disorders, and malignancies by modulating aberrant calcium signaling [4, 6].

Other names

STIM1STIM2GOKStromal interaction molecule 1Stromal interaction molecule 2D11S4896EIMD10STRMKTAMTAM1

Inhibition of STIM-Orai interaction and blockade of store-operated calcium entry (SOCE)