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Gene Review

STIM1  -  stromal interaction molecule 1

Homo sapiens

Synonyms: D11S4896E, GOK, IMD10, STRMK, Stromal interaction molecule 1, ...
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Disease relevance of STIM1


Psychiatry related information on STIM1

  • Such cognitive functions as attention, memory, executive function and problem solving were evaluated using subtests of STIM [6].

High impact information on STIM1

  • STIM1, the putative calcium sensor in the endoplasmic reticulum, and the calcium release-activated calcium (CRAC) modulator CRACM1 (also known as Orai1) in the plasma membrane have recently been shown to be essential for controlling the store-operated CRAC current (I(CRAC)) [7].
  • Overexpression of both proteins greatly potentiates I(CRAC), suggesting that STIM1 and CRACM1 mutually limit store-operated currents and that CRACM1 may be the long-sought CRAC channel [7].
  • Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane [8].
  • CRAC channels open only in the immediate vicinity of STIM1 puncta, restricting Ca(2+) entry to discrete sites comprising a small fraction of the cell surface [9].
  • Stromal interacting molecule 1 (STIM1), reported to be an endoplasmic reticulum (ER) Ca(2+) sensor controlling store-operated Ca(2+) entry, redistributes from a diffuse ER localization into puncta at the cell periphery after store depletion [8].

Biological context of STIM1

  • Mutants in the EF hand and cytoplasmic C terminus of STIM1 alter operational parameters of CRAC channels, including pharmacological profile and inactivation properties [10].
  • As a cell surface signaling protein, STIM1 represents a key pharmacological target to control fundamental Ca(2+)-regulated processes including secretion, contraction, metabolism, cell division, and apoptosis [10].
  • Introducing a point mutation in the STIM1 Ca(2+) binding domain resulted in prelocalization of the protein in puncta, and this mutant failed to respond to store depletion [11].
  • The genetic tools developed in the present work will help to determine whether pathogenetic mechanisms that associate STIM1 with tumorigenesis involve mutations in coding sequences and/or promoter, and whether methylation could determine STIM1 transcriptional down-regulation in tumor samples [1].
  • Here, we describe the STIM1 genomic organization including the identification of the promoter region [1].

Anatomical context of STIM1


Associations of STIM1 with chemical compounds


Physical interactions of STIM1

  • Direct Ca(2+) entry into the store is regulated by its filling status in a negative and positive manner through a Ca(2+)-binding protein and Stim1/Orai complex, respectively [19].

Regulatory relationships of STIM1

  • Store depletion induces redistribution of STIM1 into distinct "puncta." STIM2 translocates into puncta upon store depletion only when coexpressed with STIM1 [14].
  • Aggregation of STIM1 underneath the plasma membrane induces clustering of Orai1 [20].

Other interactions of STIM1

  • Here, we monitored receptor-triggered Ca(2+) signals in cells transfected with siRNAs against 2,304 human signaling proteins, and we identified two proteins required for Ca(2+)-store-depletion-mediated Ca(2+) influx, STIM1 and STIM2 [11].
  • However, these experiments did not establish whether Orai is an essential intracellular link between STIM and the CRAC channel, an accessory protein in the plasma membrane, or an actual pore subunit [21].
  • Restriction mapping by pulsed-field electrophoresis indicates that GOK is located 1.7 kb telomeric of RRM1, and both genes are transcribed in the same direction [22].
  • A novel gene (GOK) has been cloned from human chromosome region 11p15.5 that is believed to contain a gene or genes associated with a number of pediatric malignancies, including Wilms tumor [22].

Analytical, diagnostic and therapeutic context of STIM1


  1. Exon structure and promoter identification of STIM1 (alias GOK), a human gene causing growth arrest of the human tumor cell lines G401 and RD. Sabbioni, S., Veronese, A., Trubia, M., Taramelli, R., Barbanti-Brodano, G., Croce, C.M., Negrini, M. Cytogenet. Cell Genet. (1999) [Pubmed]
  2. STIM1: a novel phosphoprotein located at the cell surface. Manji, S.S., Parker, N.J., Williams, R.T., van Stekelenburg, L., Pearson, R.B., Dziadek, M., Smith, P.J. Biochim. Biophys. Acta (2000) [Pubmed]
  3. Identification and characterization of the STIM (stromal interaction molecule) gene family: coding for a novel class of transmembrane proteins. Williams, R.T., Manji, S.S., Parker, N.J., Hancock, M.S., Van Stekelenburg, L., Eid, J.P., Senior, P.V., Kazenwadel, J.S., Shandala, T., Saint, R., Smith, P.J., Dziadek, M.A. Biochem. J. (2001) [Pubmed]
  4. Murine Stim1 maps to distal chromosome 7 and is not imprinted. Overall, M.L., Parker, N.J., Scarcella, D.L., Smith, P.J., Dziadek, M. Mamm. Genome (1998) [Pubmed]
  5. GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development. Sabbioni, S., Barbanti-Brodano, G., Croce, C.M., Negrini, M. Cancer Res. (1997) [Pubmed]
  6. Frontal P300 decrement and executive dysfunction in adolescents with conduct problems. Kim, M.S., Kim, J.J., Kwon, J.S. Child psychiatry and human development. (2001) [Pubmed]
  7. Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Peinelt, C., Vig, M., Koomoa, D.L., Beck, A., Nadler, M.J., Koblan-Huberson, M., Lis, A., Fleig, A., Penner, R., Kinet, J.P. Nat. Cell Biol. (2006) [Pubmed]
  8. Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane. Wu, M.M., Buchanan, J., Luik, R.M., Lewis, R.S. J. Cell Biol. (2006) [Pubmed]
  9. The elementary unit of store-operated Ca2+ entry: local activation of CRAC channels by STIM1 at ER-plasma membrane junctions. Luik, R.M., Wu, M.M., Buchanan, J., Lewis, R.S. J. Cell Biol. (2006) [Pubmed]
  10. STIM1 has a plasma membrane role in the activation of store-operated Ca(2+) channels. Spassova, M.A., Soboloff, J., He, L.P., Xu, W., Dziadek, M.A., Gill, D.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Liou, J., Kim, M.L., Heo, W.D., Jones, J.T., Myers, J.W., Ferrell, J.E., Meyer, T. Curr. Biol. (2005) [Pubmed]
  12. Stromal interaction molecule 1 (STIM1), a transmembrane protein with growth suppressor activity, contains an extracellular SAM domain modified by N-linked glycosylation. Williams, R.T., Senior, P.V., Van Stekelenburg, L., Layton, J.E., Smith, P.J., Dziadek, M.A. Biochim. Biophys. Acta (2002) [Pubmed]
  13. Dynamic Assembly of TRPC1-STIM1-Orai1 Ternary Complex Is Involved in Store-operated Calcium Influx: EVIDENCE FOR SIMILARITIES IN STORE-OPERATED AND CALCIUM RELEASE-ACTIVATED CALCIUM CHANNEL COMPONENTS. Ong, H.L., Cheng, K.T., Liu, X., Bandyopadhyay, B.C., Paria, B.C., Soboloff, J., Pani, B., Gwack, Y., Srikanth, S., Singh, B.B., Gill, D., Ambudkar, I.S. J. Biol. Chem. (2007) [Pubmed]
  14. STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ Entry. Soboloff, J., Spassova, M.A., Hewavitharana, T., He, L.P., Xu, W., Johnstone, L.S., Dziadek, M.A., Gill, D.L. Curr. Biol. (2006) [Pubmed]
  15. Calcium signals mediated by STIM and Orai proteins-A new paradigm in inter-organelle communication. Soboloff, J., Spassova, M.A., Dziadek, M.A., Gill, D.L. Biochim. Biophys. Acta (2006) [Pubmed]
  16. A key role for STIM1 in store operated calcium channel activation in airway smooth muscle. Peel, S.E., Liu, B., Hall, I.P. Respir. Res. (2006) [Pubmed]
  17. Role of the microtubule cytoskeleton in the function of the store-operated Ca2+ channel activator STIM1. Smyth, J.T., DeHaven, W.I., Bird, G.S., Putney, J.W. J. Cell. Sci. (2007) [Pubmed]
  18. Lipid rafts determine clustering of STIM1 in endoplasmic reticulum-plasma membrane junctions and regulation of store-operated Ca2+ entry (SOCE). Pani, B., Ong, H.L., Liu, X., Rauser, K., Ambudkar, I.S., Singh, B.B. J. Biol. Chem. (2008) [Pubmed]
  19. Calcium signaling in non-excitable cells: Ca(2+) release and influx are independent events linked to two plasma membrane Ca(2+) entry channels. Chakrabarti, R., Chakrabarti, R. J. Cell. Biochem. (2006) [Pubmed]
  20. Aggregation of STIM1 underneath the plasma membrane induces clustering of Orai1. Xu, P., Lu, J., Li, Z., Yu, X., Chen, L., Xu, T. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  21. Orai1 is an essential pore subunit of the CRAC channel. Prakriya, M., Feske, S., Gwack, Y., Srikanth, S., Rao, A., Hogan, P.G. Nature (2006) [Pubmed]
  22. Molecular cloning of a novel human gene (D11S4896E) at chromosomal region 11p15.5. Parker, N.J., Begley, C.G., Smith, P.J., Fox, R.M. Genomics (1996) [Pubmed]
  23. Effect of voluntary vs. artificial activation on the relationship of muscle torque to speed. Dudley, G.A., Harris, R.T., Duvoisin, M.R., Hather, B.M., Buchanan, P. J. Appl. Physiol. (1990) [Pubmed]
  24. Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease. Schneider, F., Habel, U., Volkmann, J., Regel, S., Kornischka, J., Sturm, V., Freund, H.J. Arch. Gen. Psychiatry (2003) [Pubmed]
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