STIM1

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Template:Short description Template:Infobox gene Stromal interaction molecule 1 is a protein that in humans is encoded by the STIM1 gene.[1][2][3] STIM1 has a single transmembrane domain, and is localized to the endoplasmic reticulum, and to a lesser extent to the plasma membrane.[4]

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.[5][6] 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.[7][8][9] STIM1-mediated calcium entry is required for thrombin-induced disassembly of VE-cadherin adherens junctions.[10] 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.[11]

Interactions

STIM1 has been shown to interact with ORAI1, TMEM110 (STIMATE[12]), SERCA, TMEM66 (SARAF), and STIM2.[2]

Clinical relevance

STIM1 mutations are associated with Immunodeficiency 10, Tubular aggregate myopathy type 1 (TAM1), and Stormorken syndrome.[13]

References

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