{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T09:58:02Z","timestamp":1794650282950,"version":"4.9.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T00:00:00Z","timestamp":1547424000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Immunol"],"published-print":{"date-parts":[[2019,2]]},"DOI":"10.1038\/s41590-018-0287-8","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T08:17:44Z","timestamp":1545380264000},"page":"152-162","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":378,"title":["The Ca2+ sensor STIM1 regulates the type I interferon response by retaining the signaling adaptor STING at the endoplasmic reticulum"],"prefix":"10.1038","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-095X","authenticated-orcid":false,"given":"Sonal","family":"Srikanth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Seok","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4791-3475","authenticated-orcid":false,"given":"Yasser M.","family":"El-Sherbiny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koollawat","family":"Chupradit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil Ju","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Calmettes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandran","family":"Ramakrishna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2352-710X","authenticated-orcid":false,"given":"Edouard","family":"Cantin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Sung","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4559-8774","authenticated-orcid":false,"given":"Jae U.","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7910-0554","authenticated-orcid":false,"given":"Sinisa","family":"Savic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2821-9245","authenticated-orcid":false,"given":"Yousang","family":"Gwack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,14]]},"reference":[{"key":"287_CR1","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/nature07317","volume":"455","author":"H Ishikawa","year":"2008","unstructured":"Ishikawa, H. & Barber, G. N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455, 674\u2013678 (2008).","journal-title":"Nature"},{"key":"287_CR2","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.immuni.2008.09.003","volume":"29","author":"B Zhong","year":"2008","unstructured":"Zhong, B. et al. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 29, 538\u2013550 (2008).","journal-title":"Immunity"},{"key":"287_CR3","doi-asserted-by":"publisher","first-page":"8653","DOI":"10.1073\/pnas.0900850106","volume":"106","author":"W Sun","year":"2009","unstructured":"Sun, W. et al. ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. Proc. Natl Acad. Sci. USA 106, 8653\u20138658 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"287_CR4","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/nri3921","volume":"15","author":"GN Barber","year":"2015","unstructured":"Barber, G. N. STING: infection, inflammation and cancer. Nat. Rev. Immunol. 15, 760\u2013770 (2015).","journal-title":"Nat. Rev. Immunol."},{"key":"287_CR5","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/ni.3558","volume":"17","author":"Q Chen","year":"2016","unstructured":"Chen, Q., Sun, L. & Chen, Z. J. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat. Immunol. 17, 1142\u20131149 (2016).","journal-title":"Nat. Immunol."},{"key":"287_CR6","first-page":"1142","volume":"17","author":"T Li","year":"2018","unstructured":"Li, T. & Chen, Z. J. The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer. J. Exp. Med. 17, 1142\u20131149 (2018).","journal-title":"J. Exp. Med."},{"key":"287_CR7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12950-017-0159-2","volume":"14","author":"Y Li","year":"2017","unstructured":"Li, Y., Wilson, H. L. & Kiss-Toth, E. Regulating STING in health and disease. J. Inflamm. (Lond.) 14, 11 (2017).","journal-title":"J. Inflamm. (Lond.)"},{"key":"287_CR8","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/ni.1941","volume":"11","author":"N Yan","year":"2010","unstructured":"Yan, N., Regalado-Magdos, A. D., Stiggelbout, B., Lee-Kirsch, M. A. & Lieberman, J. The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. Nat. Immunol. 11, 1005\u20131013 (2010).","journal-title":"Nat. Immunol."},{"key":"287_CR9","doi-asserted-by":"publisher","first-page":"19386","DOI":"10.1073\/pnas.1215006109","volume":"109","author":"J Ahn","year":"2012","unstructured":"Ahn, J., Gutman, D., Saijo, S. & Barber, G. N. STING manifests self DNA-dependent inflammatory disease. Proc. Natl Acad. Sci. USA 109, 19386\u201319391 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"287_CR10","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/nri3850","volume":"15","author":"YJ Crow","year":"2015","unstructured":"Crow, Y. J. & Manel, N. Aicardi\u2013Goutieres syndrome and the type I interferonopathies. Nat. Rev. Immunol. 15, 429\u2013440 (2015).","journal-title":"Nat. Rev. Immunol."},{"key":"287_CR11","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1056\/NEJMoa1312625","volume":"371","author":"Y Liu","year":"2014","unstructured":"Liu, Y. et al. Activated STING in a vascular and pulmonary syndrome. N. Engl. J. Med. 371, 507\u2013518 (2014).","journal-title":"N. Engl. J. Med."},{"key":"287_CR12","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.jaci.2016.10.031","volume":"140","author":"I Melki","year":"2017","unstructured":"Melki, I. et al. Disease-associated mutations identify a novel region in human STING necessary for the control of type I interferon signaling. J. Allergy Clin. Immunol. 140, 543\u2013552.e545 (2017).","journal-title":"J. Allergy Clin. Immunol."},{"key":"287_CR13","doi-asserted-by":"publisher","first-page":"5516","DOI":"10.1172\/JCI79100","volume":"124","author":"N Jeremiah","year":"2014","unstructured":"Jeremiah, N. et al. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J. Clin. Invest. 124, 5516\u20135520 (2014).","journal-title":"J. Clin. Invest."},{"key":"287_CR14","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.chom.2015.07.001","volume":"18","author":"N Dobbs","year":"2015","unstructured":"Dobbs, N. et al. STING activation by translocation from the ER is associated with infection and autoinflammatory disease. Cell Host Microbe 18, 157\u2013168 (2015).","journal-title":"Cell Host Microbe"},{"key":"287_CR15","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.molcel.2013.05.022","volume":"51","author":"X Zhang","year":"2013","unstructured":"Zhang, X. et al. Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol. Cell 51, 226\u2013235 (2013).","journal-title":"Mol. Cell"},{"key":"287_CR16","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1152\/physrev.00020.2014","volume":"95","author":"M Prakriya","year":"2015","unstructured":"Prakriya, M. & Lewis, R. S. Store-operated calcium channels. Physiol. Rev. 95, 1383\u20131436 (2015).","journal-title":"Physiol. Rev."},{"key":"287_CR17","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1038\/nri3233","volume":"12","author":"S Feske","year":"2012","unstructured":"Feske, S., Skolnik, E. Y. & Prakriya, M. Ion channels and transporters in lymphocyte function and immunity. Nat. Rev. Immunol. 12, 532\u2013547 (2012).","journal-title":"Nat. Rev. Immunol."},{"key":"287_CR18","first-page":"143","volume":"393","author":"Y Baba","year":"2016","unstructured":"Baba, Y. & Kurosaki, T. Role of calcium signaling in B cell activation and biology. Curr. Top. Microbiol. Immunol. 393, 143\u2013174 (2016).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"287_CR19","doi-asserted-by":"crossref","unstructured":"Srikanth, S., Woo, J. S., Sun, Z. & Gwack, Y. Immunological disorders: regulation of Ca2+ signaling in T lymphocytes. Adv. Exp. Med. Biol. 993, 397\u2013424 (2017).","DOI":"10.1007\/978-3-319-57732-6_21"},{"key":"287_CR20","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/nyas.12938","volume":"1356","author":"RS Lacruz","year":"2015","unstructured":"Lacruz, R. S. & Feske, S. Diseases caused by mutations in ORAI1 and STIM1. Ann. N. Y. Acad. Sci. 1356, 45\u201379 (2015).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"287_CR21","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nri.2016.28","volume":"16","author":"LD Notarangelo","year":"2016","unstructured":"Notarangelo, L. D., Kim, M. S., Walter, J. E. & Lee, Y. N. Human RAG mutations: biochemistry and clinical implications. Nat. Rev. Immunol. 16, 234\u2013246 (2016).","journal-title":"Nat. Rev. Immunol."},{"key":"287_CR22","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.cell.2007.11.039","volume":"131","author":"O Brandman","year":"2007","unstructured":"Brandman, O., Liou, J., Park, W. S. & Meyer, T. STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. Cell 131, 1327\u20131339 (2007).","journal-title":"Cell"},{"key":"287_CR23","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/nrm3414","volume":"13","author":"J Soboloff","year":"2012","unstructured":"Soboloff, J., Rothberg, B. S., Madesh, M. & Gill, D. L. STIM proteins: dynamic calcium signal transducers. Nat. Rev. Mol. Cell Biol. 13, 549\u2013565 (2012).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"287_CR24","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1056\/NEJMoa0900082","volume":"360","author":"C Picard","year":"2009","unstructured":"Picard, C. et al. STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity. N. Engl. J. Med. 360, 1971\u20131980 (2009).","journal-title":"N. Engl. J. Med."},{"key":"287_CR25","doi-asserted-by":"publisher","unstructured":"Rice, A. et al. A report of novel STIM1 deficiency and 6 year follow up of two previous cases associated with mild immunological phenotype. Preprint at \n                    https:\/\/doi.org\/10.31219\/osf.io\/4duxt\n                    \n                   (2018).","DOI":"10.31219\/osf.io\/4duxt"},{"key":"287_CR26","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.chom.2016.03.001","volume":"19","author":"H Guo","year":"2016","unstructured":"Guo, H. et al. NLRX1 sequesters STING to negatively regulate the interferon response, thereby facilitating the replication of HIV-1 and DNA viruses. Cell Host Microbe 19, 515\u2013528 (2016).","journal-title":"Cell Host Microbe"},{"key":"287_CR27","doi-asserted-by":"publisher","first-page":"20842","DOI":"10.1073\/pnas.0911267106","volume":"106","author":"T Saitoh","year":"2009","unstructured":"Saitoh, T. et al. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc. Natl Acad. Sci. USA 106, 20842\u201320846 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"287_CR28","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1126\/science.aab3291","volume":"350","author":"L Lau","year":"2015","unstructured":"Lau, L., Gray, E. E., Brunette, R. L. & Stetson, D. B. DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway. Science 350, 568\u2013571 (2015).","journal-title":"Science"},{"key":"287_CR29","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/ncb1842","volume":"11","author":"JP Yuan","year":"2009","unstructured":"Yuan, J. P. et al. SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat. Cell Biol. 11, 337\u2013343 (2009).","journal-title":"Nat. Cell Biol."},{"key":"287_CR30","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/nature08476","volume":"461","author":"H Ishikawa","year":"2009","unstructured":"Ishikawa, H., Ma, Z. & Barber, G. N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461, 788\u2013792 (2009).","journal-title":"Nature"},{"key":"287_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11932","volume":"7","author":"K Mukai","year":"2016","unstructured":"Mukai, K. et al. Activation of STING requires palmitoylation at the Golgi. Nat. Commun. 7, 11932 (2016).","journal-title":"Nat. Commun."},{"key":"287_CR32","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.immuni.2012.03.019","volume":"36","author":"S Ouyang","year":"2012","unstructured":"Ouyang, S. et al. Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding. Immunity 36, 1073\u20131086 (2012).","journal-title":"Immunity"},{"key":"287_CR33","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1126\/science.1240933","volume":"341","author":"D Gao","year":"2013","unstructured":"Gao, D. et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science 341, 903\u2013906 (2013).","journal-title":"Science"},{"key":"287_CR34","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1083\/jcb.200301084","volume":"163","author":"N Cheshenko","year":"2003","unstructured":"Cheshenko, N. et al. Herpes simplex virus triggers activation of calcium-signaling pathways. J. Cell Biol. 163, 283\u2013293 (2003).","journal-title":"J. Cell Biol."},{"key":"287_CR35","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.immuni.2009.01.008","volume":"30","author":"B Zhong","year":"2009","unstructured":"Zhong, B. et al. The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. Immunity 30, 397\u2013407 (2009).","journal-title":"Immunity"},{"key":"287_CR36","doi-asserted-by":"publisher","first-page":"e1005012","DOI":"10.1371\/journal.ppat.1005012","volume":"11","author":"Y Wang","year":"2015","unstructured":"Wang, Y. et al. TRIM30alpha is a negative-feedback regulator of the intracellular DNA and DNA virus-triggered response by targeting STING. PLoS Pathog. 11, e1005012 (2015).","journal-title":"PLoS Pathog."},{"key":"287_CR37","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/ncb2045","volume":"12","author":"S Srikanth","year":"2010","unstructured":"Srikanth, S. et al. A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells. Nat. Cell Biol. 12, 436\u2013446 (2010).","journal-title":"Nat. Cell Biol."},{"key":"287_CR38","doi-asserted-by":"publisher","first-page":"5209","DOI":"10.1128\/MCB.00360-08","volume":"28","author":"Y Gwack","year":"2008","unstructured":"Gwack, Y. et al. Hair loss and defective T- and B-cell function in mice lacking ORAI1. Mol. Cell. Biol. 28, 5209\u20135222 (2008).","journal-title":"Mol. Cell. Biol."},{"key":"287_CR39","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.immuni.2005.12.003","volume":"24","author":"DB Stetson","year":"2006","unstructured":"Stetson, D. B. & Medzhitov, R. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity 24, 93\u2013103 (2006).","journal-title":"Immunity"},{"key":"287_CR40","doi-asserted-by":"publisher","first-page":"5066","DOI":"10.1074\/jbc.M109.072736","volume":"285","author":"S Srikanth","year":"2010","unstructured":"Srikanth, S., Jung, H. J., Ribalet, B. & Gwack, Y. The intracellular loop of Orai1 plays a central role in fast inactivation of Ca2+ release-activated Ca2+ channels. J. Biol. Chem. 285, 5066\u20135075 (2010).","journal-title":"J. Biol. Chem."}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41590-018-0287-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41590-018-0287-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41590-018-0287-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T17:50:48Z","timestamp":1684605048000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41590-018-0287-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,14]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["287"],"URL":"https:\/\/doi.org\/10.1038\/s41590-018-0287-8","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734855958.793559501","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.734855958.793555886","asserted-by":"object"}]},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,14]]},"assertion":[{"value":"30 April 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}