STIM1 explained

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]

Notes and References

  1. Parker NJ, Begley CG, Smith PJ, Fox RM . Molecular cloning of a novel human gene (D11S4896E) at chromosomal region 11p15.5 . Genomics . 37 . 2 . 253–6 . Oct 1996 . 8921403 . 10.1006/geno.1996.0553 .
  2. Williams RT, Manji SS, Parker NJ, Hancock MS, Van Stekelenburg L, Eid JP, Senior PV, Kazenwadel JS, Shandala T, Saint R, Smith PJ, Dziadek MA . Identification and characterization of the STIM (stromal interaction molecule) gene family: coding for a novel class of transmembrane proteins . The Biochemical Journal . 357 . Pt 3 . 673–85 . Aug 2001 . 11463338 . 1221997 . 10.1042/0264-6021:3570673 .
  3. Williams RT, Senior PV, Van Stekelenburg L, Layton JE, Smith PJ, Dziadek MA . 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 (BBA) - Protein Structure and Molecular Enzymology . 1596 . 1 . 131–7 . Apr 2002 . 11983428 . 10.1016/S0167-4838(02)00211-X .
  4. Soboloff J, Rothberg BS, Madesh M, Gill DL . STIM proteins: dynamic calcium signal transducers . Nature Reviews Molecular Cell Biology . 13 . 9 . 549–65 . Sep 2012 . 22914293 . 3458427 . 10.1038/nrm3414 .
  5. Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Veliçelebi G, Stauderman KA . STIM1, an essential and conserved component of store-operated Ca2+ channel function . The Journal of Cell Biology . 169 . 3 . 435–45 . May 2005 . 15866891 . 2171946 . 10.1083/jcb.200502019 .
  6. Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE, Meyer T . STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx . Current Biology . 15 . 13 . 1235–41 . Jul 2005 . 16005298 . 3186072 . 10.1016/j.cub.2005.05.055 .
  7. Putney JW . Capacitative calcium entry: from concept to molecules . Immunological Reviews . 231 . 1 . 10–22 . Sep 2009 . 19754887 . 10.1111/j.1600-065X.2009.00810.x . 32303982 .
  8. Zhou Y, Srinivasan P, Razavi S, Seymour S, Meraner P, Gudlur A, Stathopulos PB, Ikura M, Rao A, Hogan PG . Initial activation of STIM1, the regulator of store-operated calcium entry . Nature Structural & Molecular Biology . 20 . 8 . 973–81 . Aug 2013 . 23851458 . 3784406 . 10.1038/nsmb.2625 .
  9. Ma G, Wei M, He L, Liu C, Wu B, Zhang SL, Jing J, Liang X, Senes A, Tan P, Li S, Sun A, Bi Y, Zhong L, Si H, Shen Y, Li M, Lee MS, Zhou W, Wang J, Wang Y, Zhou Y . Inside-out Ca(2+) signalling prompted by STIM1 conformational switch . Nature Communications . 6 . 7826 . 2015-07-17 . 26184105 . 4509486 . 10.1038/ncomms8826 . 2015NatCo...6.7826M .
  10. Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, Malik AB, Tiruppathi C . 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 . 312. 6. L1003–L1017. Apr 2017 . 28385807 . 10.1152/ajplung.00008.2017 . 5495943 .
  11. Zeng B, Chen GL, Xu SZ . Store-independent pathways for cytosolic STIM1 clustering in the regulation of store-operated Ca(2+) influx . Biochemical Pharmacology . 84 . 8 . 1024–35 . Oct 2012 . 22842488 . 10.1016/j.bcp.2012.07.013 .
  12. Jing J, He L, Sun A, Quintana A, Ding Y, Ma G, Tan P, Liang X, Zheng X, Chen L, Shi X, Zhang SL, Zhong L, Huang Y, Dong MQ, Walker CL, Hogan PG, Wang Y, Zhou Y . Proteomic mapping of ER-PM junctions identifies STIMATE as a regulator of Ca(2+) influx . Nature Cell Biology . Aug 2015 . 26322679 . 10.1038/ncb3234 . 17 . 10 . 1339–47 . 4589512.
  13. Web site: STROMAL INTERACTION MOLECULE 1; STIM1 . 2023-11-13 . www.omim.org . en-us.

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