Even though the protein has been identified earlier, its function was unknown until recently. In 2005, it was discovered that STIM1 functions as a calcium sensor in the endoplasmic reticulum. Upon activation of the IP3 receptor, the calcium concentration in the endoplasmic reticulum decreases, which is sensed by STIM1, via its EF hand domain. STIM1 activates the "store-operated" ORAI1 calcium ion channels in the plasma membrane, via intracellular STIM1 movement, clustering under plasma membrane and protein protein interaction with ORAI isoforms. STIM1-mediated calcium entry is required for thrombin-induced disassembly of VE-cadherinadherens junctions.2-Aminoethoxydiphenyl borate (2-APB) and 4-chloro-3-ethylphenol (4-CEP) cause STIM1 clustering in a cell and prevent STIM1 moving toward plasma membrane.
^Parker NJ, Begley CG, Smith PJ, Fox RM (Oct 1996). "Molecular cloning of a novel human gene (D11S4896E) at chromosomal region 11p15.5". Genomics. 37 (2): 253–6. doi:10.1006/geno.1996.0553. PMID8921403.
^Williams RT, Senior PV, Van Stekelenburg L, Layton JE, Smith PJ, Dziadek MA (Apr 2002). "Stromal interaction molecule 1 (STIM1), a transmembrane protein with growth suppressor activity, contains an extracellular SAM domain modified by N-linked glycosylation". Biochimica et Biophysica Acta. 1596 (1): 131–7. doi:10.1016/S0167-4838(02)00211-X. PMID11983428.
^Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, Malik AB, Tiruppathi C (Apr 2017). "Pyk2 Phosphorylation of VE-PTP Downstream of STIM1 induced Ca2+ entry Regulates Disassembly of Adherens Junctions". American Journal of Physiology. Lung Cellular and Molecular Physiology. doi:10.1152/ajplung.00008.2017. PMID28385807.
^Zeng B, Chen GL, Xu SZ (Oct 2012). "Store-independent pathways for cytosolic STIM1 clustering in the regulation of store-operated Ca(2+) influx". Biochemical Pharmacology. 84 (8): 1024–35. doi:10.1016/j.bcp.2012.07.013. PMID22842488.