STIM1

Stromal interaction molecule 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2K60​, 2MAJ​, 2MAK​, 3TEQ​, 4O9B​
Identifiers
Symbols	STIM1 ; D11S4896E; GOK; IMD10; STRMK; TAM; TAM1
External IDs	OMIM: 605921 MGI: 107476 HomoloGene: 20681 GeneCards: STIM1 Gene
Gene ontology Molecular function • protease binding • calcium channel regulator activity • calcium ion binding • protein binding • identical protein binding • microtubule plus-end binding Cellular component • endoplasmic reticulum • endoplasmic reticulum membrane • microtubule • integral component of plasma membrane • integral component of endoplasmic reticulum membrane • cortical endoplasmic reticulum Biological process • detection of calcium ion • calcium ion transport • blood coagulation • activation of store-operated calcium channel activity • regulation of calcium ion transport • enamel mineralization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6786	20866
Ensembl	ENSG00000167323	ENSMUSG00000030987
UniProt	Q13586	P70302
RefSeq (mRNA)	NM_001277961	NM_009287
RefSeq (protein)	NP_001264890	NP_033313
Location (UCSC)	Chr 11: 3.85 – 4.09 Mb	Chr 7: 102.27 – 102.44 Mb
PubMed search

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 protein interaction with ORAI isoforms.^[7][8][9] 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.^[10]

Interactions

STIM1 has been shown to interact with ORAI1, TMEM110 (STIMATE^[11]), SERCA, TMEM66 (SARAF), and STIM2.^[2]

References

1. 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. PMID 8921403.
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 (Aug 2001). "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. doi:10.1042/0264-6021:3570673. PMC 1221997. PMID 11463338.
3. 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. PMID 11983428.
4. Soboloff J, Rothberg BS, Madesh M, Gill DL (Sep 2012). "STIM proteins: dynamic calcium signal transducers". Nature Reviews Molecular Cell Biology 13 (9): 549–65. doi:10.1038/nrm3414. PMC 3458427. PMID 22914293.
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 (May 2005). "STIM1, an essential and conserved component of store-operated Ca2+ channel function". The Journal of Cell Biology 169 (3): 435–45. doi:10.1083/jcb.200502019. PMC 2171946. PMID 15866891.
6. Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE, Meyer T (Jul 2005). "STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx". Current Biology 15 (13): 1235–41. doi:10.1016/j.cub.2005.05.055. PMC 3186072. PMID 16005298.
7. Putney JW (Sep 2009). "Capacitative calcium entry: from concept to molecules". Immunological Reviews 231 (1): 10–22. doi:10.1111/j.1600-065X.2009.00810.x. PMID 19754887.
8. Zhou Y, Srinivasan P, Razavi S, Seymour S, Meraner P, Gudlur A, Stathopulos PB, Ikura M, Rao A, Hogan PG (Aug 2013). "Initial activation of STIM1, the regulator of store-operated calcium entry". Nature Structural & Molecular Biology 20 (8): 973–81. doi:10.1038/nsmb.2625. PMC 3784406. PMID 23851458.
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 (2015-07-17). "Inside-out Ca(2+) signalling prompted by STIM1 conformational switch". Nature Communications 6: 7826. doi:10.1038/ncomms8826. PMC 4509486. PMID 26184105.
10. 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.x. PMID 22842488.
11. 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 (Aug 2015). "Proteomic mapping of ER-PM junctions identifies STIMATE as a regulator of Ca(2+) influx". Nature Cell Biology 17: 1339–47. doi:10.1038/ncb3234. PMID 26322679.