NMR structure of calcium-loaded STIM1 EF-SAMNMR structure of calcium-loaded STIM1 EF-SAM
Structural highlights
2k60 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
STIM1_HUMAN Defects in STIM1 are the cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 2 (IDTICED2) [MIM:612783. IDTICED2 is an immune disorder characterized by recurrent infections, impaired T-cell activation and proliferative response, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, non-progressive myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition.[1]
Function
STIM1_HUMAN Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit, TMEM142A/ORAI1.[2][3][4][5][6][7][8][9][10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
↑Picard C, McCarl CA, Papolos A, Khalil S, Luthy K, Hivroz C, LeDeist F, Rieux-Laucat F, Rechavi G, Rao A, Fischer A, Feske S. STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity. N Engl J Med. 2009 May 7;360(19):1971-80. doi: 10.1056/NEJMoa0900082. PMID:19420366 doi:http://dx.doi.org/10.1056/NEJMoa0900082
↑Sabbioni S, Barbanti-Brodano G, Croce CM, Negrini M. GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development. Cancer Res. 1997 Oct 15;57(20):4493-7. PMID:9377559
↑Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr, Meyer T. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol. 2005 Jul 12;15(13):1235-41. PMID:16005298 doi:10.1016/j.cub.2005.05.055
↑Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Velicelebi G, Stauderman KA. STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol. 2005 May 9;169(3):435-45. Epub 2005 May 2. PMID:15866891 doi:jcb.200502019
↑Zhang SL, Yu Y, Roos J, Kozak JA, Deerinck TJ, Ellisman MH, Stauderman KA, Cahalan MD. STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature. 2005 Oct 6;437(7060):902-5. PMID:16208375 doi:nature04147
↑Mercer JC, Dehaven WI, Smyth JT, Wedel B, Boyles RR, Bird GS, Putney JW Jr. Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1. J Biol Chem. 2006 Aug 25;281(34):24979-90. Epub 2006 Jun 28. PMID:16807233 doi:M604589200
↑Peinelt C, Vig M, Koomoa DL, Beck A, Nadler MJ, Koblan-Huberson M, Lis A, Fleig A, Penner R, Kinet JP. Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Nat Cell Biol. 2006 Jul;8(7):771-3. Epub 2006 May 30. PMID:16733527 doi:ncb1435
↑Spassova MA, Soboloff J, He LP, Xu W, Dziadek MA, Gill DL. STIM1 has a plasma membrane role in the activation of store-operated Ca(2+) channels. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4040-5. Epub 2006 Mar 6. PMID:16537481 doi:0510050103
↑Palty R, Raveh A, Kaminsky I, Meller R, Reuveny E. SARAF inactivates the store operated calcium entry machinery to prevent excess calcium refilling. Cell. 2012 Apr 13;149(2):425-38. doi: 10.1016/j.cell.2012.01.055. Epub 2012 Mar, 29. PMID:22464749 doi:10.1016/j.cell.2012.01.055
