Stromal interaction molecule 1 is a protein that in humans is encoded by the STIM1 gene.[5][6][7] STIM1 has a single transmembrane domain, and is localized to the endoplasmic reticulum, and to a lesser extent to the plasma membrane.[8]
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.[9][10] 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 interaction with ORAI isoforms.[11][12][13] STIM1-mediated calcium entry is required for thrombin-induced disassembly of VE-cadherin adherens junctions.[14] 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.[15]
Interactions
STIM1 has been shown to interact with ORAI1, TMEM110 (STIMATE[16]), SERCA, TMEM66 (SARAF), and STIM2.[6]
Clinical relevance
STIM1 mutations are associated with Immunodeficiency 10, Tubular aggregate myopathy type 1 (TAM1), and Stormorken syndrome.[17]