ID STING_HUMAN Reviewed; 379 AA. AC Q86WV6; A8K3P6; B6EB35; D6RBX0; D6RE01; D6RID9; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 27-MAR-2024, entry version 163. DE RecName: Full=Stimulator of interferon genes protein {ECO:0000303|PubMed:18724357}; DE Short=hSTING {ECO:0000303|PubMed:18724357, ECO:0000303|PubMed:23910378, ECO:0000303|PubMed:26669264}; DE AltName: Full=Endoplasmic reticulum interferon stimulator {ECO:0000303|PubMed:19433799}; DE Short=ERIS {ECO:0000303|PubMed:19433799}; DE AltName: Full=Mediator of IRF3 activation {ECO:0000303|PubMed:18818105, ECO:0000303|PubMed:19285439}; DE Short=hMITA {ECO:0000303|PubMed:18818105, ECO:0000303|PubMed:19285439}; DE AltName: Full=Transmembrane protein 173 {ECO:0000305}; GN Name=STING1 {ECO:0000312|HGNC:HGNC:27962}; GN Synonyms=ERIS {ECO:0000303|PubMed:19433799}, MITA GN {ECO:0000303|PubMed:18818105, ECO:0000303|PubMed:19285439}, STING GN {ECO:0000303|PubMed:18724357, ECO:0000303|PubMed:26669264}, TMEM173 GN {ECO:0000312|HGNC:HGNC:27962}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, INTERACTION WITH MAVS, PHOSPHORYLATION AT SER-358, AND RP MUTAGENESIS OF 324-SER--SER-326 AND SER-358. RX PubMed=18818105; DOI=10.1016/j.immuni.2008.09.003; RA Zhong B., Yang Y., Li S., Wang Y.-Y., Li Y., Diao F., Lei C., He X., RA Zhang L., Tien P., Shu H.-B.; RT "The adaptor protein MITA links virus-sensing receptors to IRF3 RT transcription factor activation."; RL Immunity 29:538-550(2008). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-232. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH RP RIGI AND SSR2. RX PubMed=18724357; DOI=10.1038/nature07317; RA Ishikawa H., Barber G.N.; RT "STING is an endoplasmic reticulum adaptor that facilitates innate immune RT signalling."; RL Nature 455:674-678(2008). RN [6] RP UBIQUITINATION AT LYS-150, INTERACTION WITH RNF5, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF LYS-150. RX PubMed=19285439; DOI=10.1016/j.immuni.2009.01.008; RA Zhong B., Zhang L., Lei C., Li Y., Mao A.P., Yang Y., Wang Y.Y., RA Zhang X.L., Shu H.B.; RT "The ubiquitin ligase RNF5 regulates antiviral responses by mediating RT degradation of the adaptor protein MITA."; RL Immunity 30:397-407(2009). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19776740; DOI=10.1038/nature08476; RA Ishikawa H., Ma Z., Barber G.N.; RT "STING regulates intracellular DNA-mediated, type I interferon-dependent RT innate immunity."; RL Nature 461:788-792(2009). RN [8] RP INTERACTION WITH IFIT1; IFIT2; MAVS AND TBK1. RX PubMed=19416887; DOI=10.1073/pnas.0900818106; RA Li Y., Li C., Xue P., Zhong B., Mao A.P., Ran Y., Chen H., Wang Y.Y., RA Yang F., Shu H.B.; RT "ISG56 is a negative-feedback regulator of virus-triggered signaling and RT cellular antiviral response."; RL Proc. Natl. Acad. Sci. U.S.A. 106:7945-7950(2009). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, HOMODIMERIZATION, PHOSPHORYLATION, RP UBIQUITINATION, AND MUTAGENESIS OF 76-ARG--ARG-78 AND 178-ARG--ARG-180. RX PubMed=19433799; DOI=10.1073/pnas.0900850106; RA Sun W., Li Y., Chen L., Chen H., You F., Zhou X., Zhou Y., Zhai Z., RA Chen D., Jiang Z.; RT "ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune RT signaling through dimerization."; RL Proc. Natl. Acad. Sci. U.S.A. 106:8653-8658(2009). RN [10] RP INTERACTION WITH TOMM70. RX PubMed=20628368; DOI=10.1038/cr.2010.103; RA Liu X.Y., Wei B., Shi H.X., Shan Y.F., Wang C.; RT "Tom70 mediates activation of interferon regulatory factor 3 on RT mitochondria."; RL Cell Res. 20:994-1011(2010). RN [11] RP FUNCTION, HOMODIMERIZATION, UBIQUITINATION AT LYS-150, AND MUTAGENESIS OF RP LYS-20; LYS-137 AND LYS-150. RX PubMed=21074459; DOI=10.1016/j.immuni.2010.10.013; RA Tsuchida T., Zou J., Saitoh T., Kumar H., Abe T., Matsuura Y., Kawai T., RA Akira S.; RT "The ubiquitin ligase TRIM56 regulates innate immune responses to RT intracellular double-stranded DNA."; RL Immunity 33:765-776(2010). RN [12] RP FUNCTION, AND C-DI-GMP-BINDING. RX PubMed=21947006; DOI=10.1038/nature10429; RA Burdette D.L., Monroe K.M., Sotelo-Troha K., Iwig J.S., Eckert B., RA Hyodo M., Hayakawa Y., Vance R.E.; RT "STING is a direct innate immune sensor of cyclic di-GMP."; RL Nature 478:515-518(2011). RN [13] RP FUNCTION. RX PubMed=23027953; DOI=10.1073/pnas.1211302109; RA Orzalli M.H., DeLuca N.A., Knipe D.M.; RT "Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection RT and degradation of IFI16 by the viral ICP0 protein."; RL Proc. Natl. Acad. Sci. U.S.A. 109:E3008-E3017(2012). RN [14] RP FUNCTION, INTERACTION WITH IRF3, AND MUTAGENESIS OF VAL-341; THR-342; RP SER-358; GLU-360; SER-366; GLY-367; LEU-374; ARG-375 AND ASP-377. RX PubMed=22394562; DOI=10.1126/scisignal.2002521; RA Tanaka Y., Chen Z.J.; RT "STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA RT signaling pathway."; RL Sci. Signal. 5:RA20-RA20(2012). RN [15] RP FUNCTION. RX PubMed=23707065; DOI=10.1016/j.celrep.2013.05.009; RA Diner E.J., Burdette D.L., Wilson S.C., Monroe K.M., Kellenberger C.A., RA Hyodo M., Hayakawa Y., Hammond M.C., Vance R.E.; RT "The innate immune DNA sensor cGAS produces a noncanonical cyclic RT dinucleotide that activates human STING."; RL Cell Rep. 3:1355-1361(2013). RN [16] RP FUNCTION. RX PubMed=23722158; DOI=10.1038/nature12306; RA Ablasser A., Goldeck M., Cavlar T., Deimling T., Witte G., Rohl I., RA Hopfner K.P., Ludwig J., Hornung V.; RT "cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that RT activates STING."; RL Nature 498:380-384(2013). RN [17] RP FUNCTION. RX PubMed=23258412; DOI=10.1126/science.1229963; RA Wu J., Sun L., Chen X., Du F., Shi H., Chen C., Chen Z.J.; RT "Cyclic GMP-AMP is an endogenous second messenger in innate immune RT signaling by cytosolic DNA."; RL Science 339:826-830(2013). RN [18] RP INTERACTION WITH ZDHHC1, AND REGION. RX PubMed=25299331; DOI=10.1016/j.chom.2014.09.006; RA Zhou Q., Lin H., Wang S., Wang S., Ran Y., Liu Y., Ye W., Xiong X., RA Zhong B., Shu H.B., Wang Y.Y.; RT "The ER-associated protein ZDHHC1 is a positive regulator of DNA virus- RT triggered, MITA/STING-dependent innate immune signaling."; RL Cell Host Microbe 16:450-461(2014). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP ACTIVITY REGULATION. RX PubMed=25344812; DOI=10.1038/nchembio.1661; RA Li L., Yin Q., Kuss P., Maliga Z., Millan J.L., Wu H., Mitchison T.J.; RT "Hydrolysis of 2'3'-cGAMP by ENPP1 and design of nonhydrolyzable analogs."; RL Nat. Chem. Biol. 10:1043-1048(2014). RN [21] RP UBIQUITINATION AT LYS-150, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP LYS-150. RX PubMed=25254379; DOI=10.1371/journal.ppat.1004358; RA Qin Y., Zhou M.T., Hu M.M., Hu Y.H., Zhang J., Guo L., Zhong B., Shu H.B.; RT "RNF26 temporally regulates virus-triggered type I interferon induction by RT two distinct mechanisms."; RL PLoS Pathog. 10:E1004358-E1004358(2014). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [23] RP MUTAGENESIS OF SER-162, AND ACTIVITY REGULATION. RX PubMed=26669264; DOI=10.1038/srep18035; RA Zhang H., Han M.J., Tao J., Ye Z.Y., Du X.X., Deng M.J., Zhang X.Y., RA Li L.F., Jiang Z.F., Su X.D.; RT "Rat and human STINGs profile similarly towards anticancer/antiviral RT compounds."; RL Sci. Rep. 5:18035-18035(2015). RN [24] RP FUNCTION, AND CHARACTERIZATION OF VARIANT ARG-232. RX PubMed=26300263; DOI=10.1016/j.molcel.2015.07.022; RA Kranzusch P.J., Wilson S.C., Lee A.S., Berger J.M., Doudna J.A., RA Vance R.E.; RT "Ancient origin of cGAS-STING reveals mechanism of universal 2',3' cGAMP RT signaling."; RL Mol. Cell 59:891-903(2015). RN [25] RP FUNCTION. RX PubMed=26229117; DOI=10.1126/science.aab3632; RA Bridgeman A., Maelfait J., Davenne T., Partridge T., Peng Y., Mayer A., RA Dong T., Kaever V., Borrow P., Rehwinkel J.; RT "Viruses transfer the antiviral second messenger cGAMP between cells."; RL Science 349:1228-1232(2015). RN [26] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH PAPILLOMAVIRUS PROTEIN RP E7 AND ADENOVIRUS EARLY E1A PROTEIN (MICROBIAL INFECTION). RX PubMed=26405230; DOI=10.1126/science.aab3291; RA Lau L., Gray E.E., Brunette R.L., Stetson D.B.; RT "DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway."; RL Science 350:568-571(2015). RN [27] RP FUNCTION, DOMAIN, INTERACTION WITH IRF3, PHOSPHORYLATION AT SER-358 AND RP SER-366, AND MUTAGENESIS OF SER-358 AND SER-366. RX PubMed=25636800; DOI=10.1126/science.aaa2630; RA Liu S., Cai X., Wu J., Cong Q., Chen X., Li T., Du F., Ren J., Wu Y.T., RA Grishin N.V., Chen Z.J.; RT "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF RT induces IRF3 activation."; RL Science 347:AAA2630-AAA2630(2015). RN [28] RP FUNCTION, AND DEUBIQUITIATION BY USP20. RX PubMed=27801882; DOI=10.1038/cr.2016.125; RA Zhang M., Zhang M.X., Zhang Q., Zhu G.F., Yuan L., Zhang D.E., Zhu Q., RA Yao J., Shu H.B., Zhong B.; RT "USP18 recruits USP20 to promote innate antiviral response through RT deubiquitinating STING/MITA."; RL Cell Res. 26:1302-1319(2016). RN [29] RP INTERACTION WITH IRF3 AND ZDHHC11, AND REGION. RX PubMed=28331227; DOI=10.1038/leu.2017.94; RA Dzikiewicz-Krawczyk A., Kok K., Slezak-Prochazka I., Robertus J.L., RA Bruining J., Tayari M.M., Rutgers B., de Jong D., Koerts J., Seitz A., RA Li J., Tillema B., Guikema J.E., Nolte I.M., Diepstra A., Visser L., RA Kluiver J., van den Berg A.; RT "ZDHHC11 and ZDHHC11B are critical novel components of the oncogenic MYC- RT miR-150-MYB network in Burkitt lymphoma."; RL Leukemia 31:1470-1473(2017). RN [30] RP DEUBIQUITINATION BY USP13. RX PubMed=28534493; DOI=10.1038/ncomms15534; RA Sun H., Zhang Q., Jing Y.Y., Zhang M., Wang H.Y., Cai Z., Liuyu T., RA Zhang Z.D., Xiong T.C., Wu Y., Zhu Q.Y., Yao J., Shu H.B., Lin D., RA Zhong B.; RT "USP13 negatively regulates antiviral responses by deubiquitinating RT STING."; RL Nat. Commun. 8:15534-15534(2017). RN [31] RP INTERACTION WITH TRIM29. RX PubMed=29038422; DOI=10.1038/s41467-017-00101-w; RA Xing J., Zhang A., Zhang H., Wang J., Li X.C., Zeng M.S., Zhang Z.; RT "TRIM29 promotes DNA virus infections by inhibiting innate immune RT response."; RL Nat. Commun. 8:945-945(2017). RN [32] RP MUTAGENESIS OF SER-358. RX PubMed=29478775; DOI=10.1016/j.chom.2018.01.006; RA Xie J., Li Y., Shen X., Goh G., Zhu Y., Cui J., Wang L.F., Shi Z.L., RA Zhou P.; RT "Dampened STING-dependent interferon activation in bats."; RL Cell Host Microbe 23:297-301(2018). RN [33] RP INTERACTION WITH IFI16-BETA. RX PubMed=30104205; DOI=10.15252/embr.201845737; RA Wang P.H., Ye Z.W., Deng J.J., Siu K.L., Gao W.W., Chaudhary V., Cheng Y., RA Fung S.Y., Yuen K.S., Ho T.H., Chan C.P., Zhang Y., Kok K.H., Yang W., RA Chan C.P., Jin D.Y.; RT "Inhibition of AIM2 inflammasome activation by a novel transcript isoform RT of IFI16."; RL EMBO Rep. 19:0-0(2018). RN [34] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN ICP34.5 (MICROBIAL RP INFECTION). RX PubMed=30045990; DOI=10.1128/jvi.01015-18; RA Pan S., Liu X., Ma Y., Cao Y., He B.; RT "34.5 Protein Inhibits STING Activation That Restricts Viral Replication."; RL J. Virol. 0:0-0(2018). RN [35] RP FUNCTION, ACTIVITY REGULATION, PALMITOYLATION AT CYS-91, AND MUTAGENESIS OF RP CYS-91. RX PubMed=29973723; DOI=10.1038/s41586-018-0287-8; RA Haag S.M., Gulen M.F., Reymond L., Gibelin A., Abrami L., Decout A., RA Heymann M., van der Goot F.G., Turcatti G., Behrendt R., Ablasser A.; RT "Targeting STING with covalent small-molecule inhibitors."; RL Nature 559:269-273(2018). RN [36] RP FUNCTION. RX PubMed=30568238; DOI=10.1038/s41418-018-0251-z; RA Liu D., Wu H., Wang C., Li Y., Tian H., Siraj S., Sehgal S.A., Wang X., RA Wang J., Shang Y., Jiang Z., Liu L., Chen Q.; RT "STING directly activates autophagy to tune the innate immune response."; RL Cell Death Differ. 26:1735-1749(2019). RN [37] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS RP OF 238-ARG--TYR-240; GLN-273; ALA-277; PRO-371; LEU-374 AND ARG-375. RX PubMed=30842653; DOI=10.1038/s41586-019-1000-2; RA Zhang C., Shang G., Gui X., Zhang X., Bai X.C., Chen Z.J.; RT "Structural basis of STING binding with and phosphorylation by TBK1."; RL Nature 567:394-398(2019). RN [38] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC24C, AND MUTAGENESIS OF RP 238-ARG--TYR-240; ARG-238 AND 333-LEU-ARG-334. RX PubMed=30842662; DOI=10.1038/s41586-019-1006-9; RA Gui X., Yang H., Li T., Tan X., Shi P., Li M., Du F., Chen Z.J.; RT "Autophagy induction via STING trafficking is a primordial function of the RT cGAS pathway."; RL Nature 567:262-266(2019). RN [39] RP INTERACTION WITH SURF4. RX PubMed=29251827; DOI=10.1002/pmic.201700403; RA Shang J., Xia T., Han Q.Q., Zhao X., Hu M.M., Shu H.B., Guo L.; RT "Quantitative Proteomics Identified TTC4 as a TBK1 Interactor and a RT Positive Regulator of SeV-Induced Innate Immunity."; RL Proteomics 18:0-0(2018). RN [40] RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL42 (MICROBIAL INFECTION). RX PubMed=31107917; DOI=10.1371/journal.ppat.1007691; RA Fu Y.Z., Guo Y., Zou H.M., Su S., Wang S.Y., Yang Q., Luo M.H., Wang Y.Y.; RT "Human cytomegalovirus protein UL42 antagonizes cGAS/MITA-mediated innate RT antiviral response."; RL PLoS Pathog. 15:e1007691-e1007691(2019). RN [41] RP INTERACTION WITH HNRNPA2B1. RX PubMed=31320558; DOI=10.1126/science.aav0758; RA Wang L., Wen M., Cao X.; RT "Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to RT DNA viruses."; RL Science 0:0-0(2019). RN [42] RP PHOSPHORYLATION AT SER-366, AND DEPHOSPHORYLATION. RX PubMed=32753499; DOI=10.1128/mbio.01728-20; RA Ni G., Ma Z., Wong J.P., Zhang Z., Cousins E., Major M.B., Damania B.; RT "PPP6C negatively regulates STING-dependent innate immune responses."; RL MBio 11:0-0(2020). RN [43] RP INTERACTION WITH STEEP1; SEC24A AND SEC24B, SUBCELLULAR LOCATION, DOMAIN, RP PHOSPHORYLATION AT SER-366, AND MUTAGENESIS OF 273-GLN--ALA-277. RX PubMed=32690950; DOI=10.1038/s41590-020-0730-5; RA Zhang B.C., Nandakumar R., Reinert L.S., Huang J., Laustsen A., Gao Z.L., RA Sun C.L., Jensen S.B., Troldborg A., Assil S., Berthelsen M.F., RA Scavenius C., Zhang Y., Windross S.J., Olagnier D., Prabakaran T., RA Bodda C., Narita R., Cai Y., Zhang C.G., Stenmark H., Doucet C.M., Noda T., RA Guo Z., Goldbach-Mansky R., Hartmann R., Chen Z.J., Enghild J.J., Bak R.O., RA Thomsen M.K., Paludan S.R.; RT "STEEP mediates STING ER exit and activation of signaling."; RL Nat. Immunol. 21:868-879(2020). RN [44] RP ERRATUM OF PUBMED:32690950. RX PubMed=32929276; DOI=10.1038/s41590-020-0803-5; RA Zhang B.C., Nandakumar R., Reinert L.S., Huang J., Laustsen A., Gao Z.L., RA Sun C.L., Jensen S.B., Troldborg A., Assil S., Berthelsen M.F., RA Scavenius C., Zhang Y., Windross S.J., Olagnier D., Prabakaran T., RA Bodda C., Narita R., Cai Y., Zhang C.G., Stenmark H., Doucet C.M., Noda T., RA Guo Z., Goldbach-Mansky R., Hartmann R., Chen Z.J., Enghild J.J., Bak R.O., RA Thomsen M.K., Paludan S.R.; RL Nat. Immunol. 21:1468-1469(2020). RN [45] RP INTERACTION WITH CHIKUNGUNYA VIRUS NON-STRUCTURAL PROTEIN 1 (MICROBIAL RP INFECTION). RX PubMed=33057424; DOI=10.1371/journal.ppat.1008999; RA Webb L.G., Veloz J., Pintado-Silva J., Zhu T., Rangel M.V., Mutetwa T., RA Zhang L., Bernal-Rubio D., Figueroa D., Carrau L., Fenutria R., Potla U., RA Reid S.P., Yount J.S., Stapleford K.A., Aguirre S., Fernandez-Sesma A.; RT "Chikungunya virus antagonizes cGAS-STING mediated type-I interferon RT responses by degrading cGAS."; RL PLoS Pathog. 16:e1008999-e1008999(2020). RN [46] RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL94 (MICROBIAL INFECTION). RX PubMed=32238587; DOI=10.1128/jvi.00022-20; RA Zou H.M., Huang Z.F., Yang Y., Luo W.W., Wang S.Y., Luo M.H., Fu Y.Z., RA Wang Y.Y.; RT "Human Cytomegalovirus Protein UL94 Targets MITA to Evade the Antiviral RT Immune Response."; RL J. Virol. 94:0-0(2020). RN [47] RP FUNCTION, DEUBIQUITIATION BY USP44, AND MUTAGENESIS OF LYS-236. RX PubMed=31968013; DOI=10.1371/journal.ppat.1008178; RA Zhang H.Y., Liao B.W., Xu Z.S., Ran Y., Wang D.P., Yang Y., Luo W.W., RA Wang Y.Y.; RT "USP44 positively regulates innate immune response to DNA viruses through RT deubiquitinating MITA."; RL PLoS Pathog. 16:e1008178-e1008178(2020). RN [48] RP SUBCELLULAR LOCATION, AND INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN RP UL138 (MICROBIAL INFECTION). RX PubMed=34903048; DOI=10.1128/mbio.02267-21; RA Albright E.R., Mickelson C.K., Kalejta R.F.; RT "Human Cytomegalovirus UL138 Protein Inhibits the STING Pathway and Reduces RT Interferon Beta mRNA Accumulation during Lytic and Latent Infections."; RL MBio 12:e0226721-e0226721(2021). RN [49] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=35045565; DOI=10.1038/s41586-022-04421-w; RA Di Domizio J., Gulen M.F., Saidoune F., Thacker V.V., Yatim A., Sharma K., RA Nass T., Guenova E., Schaller M., Conrad C., Goepfert C., De Leval L., RA von Garnier C., Berezowska S., Dubois A., Gilliet M., Ablasser A.; RT "The cGAS-STING pathway drives type I IFN immunopathology in COVID-19."; RL Nature 603:145-151(2022). RN [50] RP FUNCTION, INTERACTION WITH VARICELLA-ZOSTER VIRUS PROTEIN 39 (MICROBIAL RP INFECTION), AND SUBCELLULAR LOCATION. RX PubMed=36808561; DOI=10.1007/s12275-023-00019-7; RA Lee G.M., Gong S., Seo S.W., Ko H., Chung W.C., Lee J., Shin O.S., RA Ahn J.H.; RT "Varicella-Zoster Virus ORF39 Transmembrane Protein Suppresses Interferon- RT Beta Promoter Activation by Interacting with STING."; RL J. Microbiol. 0:0-0(2023). RN [51] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STEEP1 AND TAB1, RP PHOSPHORYLATION AT THR-229; SER-241; THR-354; SER-355 AND THR-356, AND RP MUTAGENESIS OF GLY-158 AND SER-355. RX PubMed=37832545; DOI=10.1016/j.molcel.2023.09.009; RA Ma M., Dang Y., Chang B., Wang F., Xu J., Chen L., Su H., Li J., Ge B., RA Chen C., Liu H.; RT "TAK1 is an essential kinase for STING trafficking."; RL Mol. Cell 0:0-0(2023). RN [52] RP DEUBIQUITINATION BY EPSTEIN-BARR VIRUS PROTEIN BPLF1 (MICROBIAL INFECTION). RX PubMed=36802409; DOI=10.1371/journal.ppat.1011186; RA Lui W.Y., Bharti A., Wong N.M., Jangra S., Botelho M.G., Yuen K.S., RA Jin D.Y.; RT "Suppression of cGAS- and RIG-I-mediated innate immune signaling by RT Epstein-Barr virus deubiquitinase BPLF1."; RL PLoS Pathog. 19:e1011186-e1011186(2023). RN [53] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION, RP AND MUTAGENESIS OF 273-GLN--ALA-277. RX PubMed=37535724; DOI=10.1126/science.adf8974; RA Liu B., Carlson R.J., Pires I.S., Gentili M., Feng E., Hellier Q., RA Schwartz M.A., Blainey P.C., Irvine D.J., Hacohen N.; RT "Human STING is a proton channel."; RL Science 381:508-514(2023). RN [54] {ECO:0007744|PDB:4EF4, ECO:0007744|PDB:4EF5} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 139-379 IN COMPLEX WITH C-DI-GMP, RP AND SUBUNIT. RX PubMed=22579474; DOI=10.1016/j.immuni.2012.03.019; RA Ouyang S., Song X., Wang Y., Ru H., Shaw N., Jiang Y., Niu F., Zhu Y., RA Qiu W., Parvatiyar K., Li Y., Zhang R., Cheng G., Liu Z.J.; RT "Structural analysis of the STING adaptor protein reveals a hydrophobic RT dimer interface and mode of cyclic di-GMP binding."; RL Immunity 36:1073-1086(2012). RN [55] {ECO:0007744|PDB:4F9E, ECO:0007744|PDB:4F9G} RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 139-379 IN COMPLEX WITH C-DI-GMP, RP AND SUBUNIT. RX PubMed=22705373; DOI=10.1016/j.molcel.2012.05.029; RA Yin Q., Tian Y., Kabaleeswaran V., Jiang X., Tu D., Eck M.J., Chen Z.J., RA Wu H.; RT "Cyclic di-GMP sensing via the innate immune signaling protein STING."; RL Mol. Cell 46:735-745(2012). RN [56] {ECO:0007744|PDB:4EMT, ECO:0007744|PDB:4EMU} RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 155-341 IN COMPLEX WITH C-DI-GMP, RP SUBUNIT, AND MUTAGENESIS OF SER-162; GLY-166; TYR-240; ASN-242; GLU-260; RP THR-263; PRO-264 AND THR-267. RX PubMed=22728658; DOI=10.1038/nsmb.2331; RA Shu C., Yi G., Watts T., Kao C.C., Li P.; RT "Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic RT dinucleotide recognition by the immune system."; RL Nat. Struct. Mol. Biol. 19:722-724(2012). RN [57] {ECO:0007744|PDB:4F5W, ECO:0007744|PDB:4F5Y} RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 149-379 IN COMPLEX WITH C-DI-GMP, RP AND SUBUNIT. RX PubMed=22728660; DOI=10.1038/nsmb.2332; RA Shang G., Zhu D., Li N., Zhang J., Zhu C., Lu D., Liu C., Yu Q., Zhao Y., RA Xu S., Gu L.; RT "Crystal structures of STING protein reveal basis for recognition of cyclic RT di-GMP."; RL Nat. Struct. Mol. Biol. 19:725-727(2012). RN [58] {ECO:0007744|PDB:4F5D, ECO:0007744|PDB:4F5E} RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 141-379 IN COMPLEX WITH C-DI-GMP, RP AND SUBUNIT. RX PubMed=22728659; DOI=10.1038/nsmb.2333; RA Huang Y.H., Liu X.Y., Du X.X., Jiang Z.F., Su X.D.; RT "The structural basis for the sensing and binding of cyclic di-GMP by RT STING."; RL Nat. Struct. Mol. Biol. 19:728-730(2012). RN [59] {ECO:0007744|PDB:4LOH, ECO:0007744|PDB:4LOI} RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 155-341 IN COMPLEX WITH CGAMP, RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF SER-162; ARG-238; RP TYR-240; ASN-242 AND GLU-260. RX PubMed=23910378; DOI=10.1016/j.cell.2013.07.023; RA Gao P., Ascano M., Zillinger T., Wang W., Dai P., Serganov A.A., RA Gaffney B.L., Shuman S., Jones R.A., Deng L., Hartmann G., Barchet W., RA Tuschl T., Patel D.J.; RT "Structure-function analysis of STING activation by c[G(2',5')pA(3',5')p] RT and targeting by antiviral DMXAA."; RL Cell 154:748-762(2013). RN [60] {ECO:0007744|PDB:4KSY} RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 138-379 IN COMPLEX WITH CGAMP, RP AND FUNCTION. RX PubMed=23747010; DOI=10.1016/j.molcel.2013.05.022; RA Zhang X., Shi H., Wu J., Zhang X., Sun L., Chen C., Chen Z.J.; RT "Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous RT high-affinity ligand for STING."; RL Mol. Cell 51:226-235(2013). RN [61] {ECO:0007744|PDB:4QXO, ECO:0007744|PDB:4QXP, ECO:0007744|PDB:4QXQ, ECO:0007744|PDB:4QXR} RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 155-341 OF MUTANTS IN COMPLEX RP WITH DMXAA, ACTIVITY REGULATION, AND MUTAGENESIS OF SER-162; GLY-230 AND RP GLN-266. RX PubMed=25199835; DOI=10.1016/j.celrep.2014.08.010; RA Gao P., Zillinger T., Wang W., Ascano M., Dai P., Hartmann G., Tuschl T., RA Deng L., Barchet W., Patel D.J.; RT "Binding-pocket and lid-region substitutions render human STING sensitive RT to the species-specific drug DMXAA."; RL Cell Rep. 8:1668-1676(2014). RN [62] {ECO:0007744|PDB:5BQX} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 138-379 IN COMPLEX WITH RP 3'2'-CGAMP. RX PubMed=26150511; DOI=10.1073/pnas.1507317112; RA Shi H., Wu J., Chen Z.J., Chen C.; RT "Molecular basis for the specific recognition of the metazoan cyclic GMP- RT AMP by the innate immune adaptor protein STING."; RL Proc. Natl. Acad. Sci. U.S.A. 112:8947-8952(2015). RN [63] {ECO:0007744|PDB:5JEJ} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 342-379, INTERACTION WITH IRF3, RP PHOSPHORYLATION AT SER-366, AND MUTAGENESIS OF SER-358; GLU-362; LEU-363; RP LEU-364; ILE-365; SER-366; THR-376 AND SER-379. RX PubMed=27302953; DOI=10.1073/pnas.1603269113; RA Zhao B., Shu C., Gao X., Sankaran B., Du F., Shelton C.L., Herr A.B., RA Ji J.Y., Li P.; RT "Structural basis for concerted recruitment and activation of IRF-3 by RT innate immune adaptor proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 113:E3403-E3412(2016). RN [64] RP STRUCTURE BY ELECTRON MICROSCOPY (4.1 ANGSTROMS) OF 1-379, FUNCTION, RP SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF ILE-10; ARG-14; RP GLU-68; GLU-69; PHE-153 AND GLY-158, AND CHARACTERIZATION OF VARIANT SAVI RP MET-155. RX PubMed=30842659; DOI=10.1038/s41586-019-0998-5; RA Shang G., Zhang C., Chen Z.J., Bai X.C., Zhang X.; RT "Cryo-EM structures of STING reveal its mechanism of activation by cyclic RT GMP-AMP."; RL Nature 567:389-393(2019). RN [65] {ECO:0007744|PDB:6MX0, ECO:0007744|PDB:6MX3, ECO:0007744|PDB:6MXE} RP X-RAY CRYSTALLOGRAPHY (1.36 ANGSTROMS) OF 155-341 IN COMPLEX WITH COMPOUND RP 18 INHIBITOR, AND ACTIVITY REGULATION. RX PubMed=30655953; DOI=10.1021/acsmedchemlett.8b00466; RA Siu T., Altman M.D., Baltus G.A., Childers M., Ellis J.M., Gunaydin H., RA Hatch H., Ho T., Jewell J., Lacey B.M., Lesburg C.A., Pan B.S., RA Sauvagnat B., Schroeder G.K., Xu S.; RT "Discovery of a novel cGAMP competitive ligand of the inactive form of RT STING."; RL ACS Med. Chem. Lett. 10:92-97(2019). RN [66] {ECO:0007744|PDB:7SII} RP STRUCTURE BY ELECTRON MICROSCOPY (3.45 ANGSTROMS) OF 1-344 IN COMPLEX WITH RP 2'3'-CGAMP, FUNCTION, ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF RP LEU-26; LEU-30; LEU-44 AND TYR-104. RX PubMed=35388221; DOI=10.1038/s41586-022-04559-7; RA Lu D., Shang G., Li J., Lu Y., Bai X.C., Zhang X.; RT "Activation of STING by targeting a pocket in the transmembrane domain."; RL Nature 604:557-562(2022). RN [67] {ECO:0007744|PDB:8GJX} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 154-341 IN COMPLEX WITH CUAMP, RP AND FUNCTION. RX PubMed=37379839; DOI=10.1016/j.cell.2023.05.038; RA Li Y., Slavik K.M., Toyoda H.C., Morehouse B.R., de Oliveira Mann C.C., RA Elek A., Levy S., Wang Z., Mears K.S., Liu J., Kashin D., Guo X., Mass T., RA Sebe-Pedros A., Schwede F., Kranzusch P.J.; RT "cGLRs are a diverse family of pattern recognition receptors in innate RT immunity."; RL Cell 186:3261-3276(2023). RN [68] RP VARIANT SAVI MET-155, AND CHARACTERIZATION OF VARIANT SAVI MET-155. RX PubMed=25401470; DOI=10.1172/jci79100; RA Jeremiah N., Neven B., Gentili M., Callebaut I., Maschalidi S., RA Stolzenberg M.C., Goudin N., Fremond M.L., Nitschke P., Molina T.J., RA Blanche S., Picard C., Rice G.I., Crow Y.J., Manel N., Fischer A., RA Bader-Meunier B., Rieux-Laucat F.; RT "Inherited STING-activating mutation underlies a familial inflammatory RT syndrome with lupus-like manifestations."; RL J. Clin. Invest. 124:5516-5520(2014). RN [69] RP VARIANTS SAVI LEU-147; SER-154 AND MET-155, AND TISSUE SPECIFICITY. RX PubMed=25029335; DOI=10.1056/nejmoa1312625; RA Liu Y., Jesus A.A., Marrero B., Yang D., Ramsey S.E., RA Montealegre Sanchez G.A., Tenbrock K., Wittkowski H., Jones O.Y., RA Kuehn H.S., Lee C.C., DiMattia M.A., Cowen E.W., Gonzalez B., Palmer I., RA DiGiovanna J.J., Biancotto A., Kim H., Tsai W.L., Trier A.M., Huang Y., RA Stone D.L., Hill S., Kim H.J., St Hilaire C., Gurprasad S., Plass N., RA Chapelle D., Horkayne-Szakaly I., Foell D., Barysenka A., Candotti F., RA Holland S.M., Hughes J.D., Mehmet H., Issekutz A.C., Raffeld M., RA McElwee J., Fontana J.R., Minniti C.P., Moir S., Kastner D.L., Gadina M., RA Steven A.C., Wingfield P.T., Brooks S.R., Rosenzweig S.D., Fleisher T.A., RA Deng Z., Boehm M., Paller A.S., Goldbach-Mansky R.; RT "Activated STING in a vascular and pulmonary syndrome."; RL N. Engl. J. Med. 371:507-518(2014). RN [70] RP VARIANT SER-284, CHARACTERIZATION OF VARIANT SER-284, AND SUBCELLULAR RP LOCATION. RX PubMed=29694889; DOI=10.1016/j.celrep.2018.03.115; RA Konno H., Chinn I.K., Hong D., Orange J.S., Lupski J.R., Mendoza A., RA Pedroza L.A., Barber G.N.; RT "Pro-inflammation associated with a gain-of-function mutation (R284S) in RT the innate immune sensor STING."; RL Cell Rep. 23:1112-1123(2018). CC -!- FUNCTION: Facilitator of innate immune signaling that acts as a sensor CC of cytosolic DNA from bacteria and viruses and promotes the production CC of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, CC PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:23027953, CC PubMed:23910378, PubMed:23747010, PubMed:29973723, PubMed:30842659, CC PubMed:35045565, PubMed:27801882, PubMed:36808561, PubMed:37832545, CC PubMed:35388221). Innate immune response is triggered in response to CC non-CpG double-stranded DNA from viruses and bacteria delivered to the CC cytoplasm (PubMed:26300263). Acts by binding cyclic dinucleotides: CC recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger CC produced by bacteria, cyclic UMP-AMP (2',3'-cUAMP), and cyclic GMP-AMP CC (cGAMP), a messenger produced by CGAS in response to DNA virus in the CC cytosol (PubMed:21947006, PubMed:23258412, PubMed:23707065, CC PubMed:23722158, PubMed:26229117, PubMed:23910378, PubMed:23747010, CC PubMed:30842659, PubMed:35388221, PubMed:37379839). Upon binding to c- CC di-GMP, cUAMP or cGAMP, STING1 oligomerizes, translocates from the CC endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, CC leading to recruitment and subsequent activation of the transcription CC factor IRF3 to induce expression of type I interferon and exert a CC potent anti-viral state (PubMed:22394562, PubMed:25636800, CC PubMed:29973723, PubMed:30842653, PubMed:35045565, PubMed:35388221). CC Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can CC bind both 2'-3' linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but CC is preferentially activated by 2'-3' linked cGAMP (PubMed:26300263, CC PubMed:23910378, PubMed:23747010). The preference for 2'-3'-cGAMP, CC compared to other linkage isomers is probably due to the ligand itself, CC whichs adopts an organized free-ligand conformation that resembles the CC STING1-bound conformation and pays low energy costs in changing into CC the active conformation (PubMed:26150511). In addition to promote the CC production of type I interferons, plays a direct role in autophagy CC (PubMed:30568238, PubMed:30842662). Following cGAMP-binding, STING1 CC buds from the endoplasmic reticulum into COPII vesicles, which then CC form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) CC (PubMed:30842662). The ERGIC serves as the membrane source for WIPI2 CC recruitment and LC3 lipidation, leading to formation of autophagosomes CC that target cytosolic DNA or DNA viruses for degradation by the CC lysosome (PubMed:30842662). Promotes autophagy by acting as a proton CC channel that directs proton efflux from the Golgi to facilitate CC MAP1LC3B/LC3B lipidation (PubMed:37535724). The autophagy- and CC interferon-inducing activities can be uncoupled and autophagy induction CC is independent of TBK1 phosphorylation (PubMed:30568238, CC PubMed:30842662). Autophagy is also triggered upon infection by CC bacteria: following c-di-GMP-binding, which is produced by live Gram- CC positive bacteria, promotes reticulophagy (By similarity). May be CC involved in translocon function, the translocon possibly being able to CC influence the induction of type I interferons (PubMed:18724357). May be CC involved in transduction of apoptotic signals via its association with CC the major histocompatibility complex class II (MHC-II) (By similarity). CC {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:18724357, CC ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, CC ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:21947006, CC ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:23027953, CC ECO:0000269|PubMed:23258412, ECO:0000269|PubMed:23707065, CC ECO:0000269|PubMed:23722158, ECO:0000269|PubMed:23747010, CC ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:25636800, CC ECO:0000269|PubMed:26150511, ECO:0000269|PubMed:26229117, CC ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:27801882, CC ECO:0000269|PubMed:29973723, ECO:0000269|PubMed:30568238, CC ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, CC ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:35045565, CC ECO:0000269|PubMed:35388221, ECO:0000269|PubMed:36808561, CC ECO:0000269|PubMed:37379839, ECO:0000269|PubMed:37535724, CC ECO:0000269|PubMed:37832545}. CC -!- FUNCTION: (Microbial infection) Antiviral activity is antagonized by CC oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus CC early E1A protein (PubMed:26405230). Such oncoproteins prevent the CC ability to sense cytosolic DNA (PubMed:26405230). CC {ECO:0000269|PubMed:26405230}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378; CC Evidence={ECO:0000269|PubMed:37535724}; CC -!- ACTIVITY REGULATION: Activated upon binding to the hydrolysis-resistant CC 2'3'-cG(s)A(s)MP, an analog of cGAMP, in which phosphodiester linkages CC are replaced by phosphothioate linkages (PubMed:25344812). Specifically CC inhibited by small-molecule H-151 (N-(4-ethylphenyl)-N'-1H-indol-3-yl- CC urea), which covalently binds Cys-91 and prevents palmitoylation and CC subsequent activation of STING1 (PubMed:29973723, PubMed:35045565). In CC contrast to mouse protein, not activated by anticancer molecule 5,6- CC dimethylxanthenone 4-acetic acid (DMXAA) (PubMed:26669264, CC PubMed:23910378, PubMed:25199835). Inhibited by compound 18 ([(3S,4S)- CC 2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7- CC fluoro-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl]acetate), a competitive CC inhibitor with slow dissociation kinetics and good oral bioavailability CC (PubMed:30655953). Homooligomerization and ability to promote the CC production of type I interferons is activated by C53, a small CC benzothiazinone-like compound that binds to the transmembrane regions. CC in the area of the putative pore (PubMed:35388221). In contrast, CC compound C53, directly inhibits the proton channel activity and CC facilitate MAP1LC3B/LC3B lipidation and autophagosome formation CC (PubMed:37535724). {ECO:0000269|PubMed:23910378, CC ECO:0000269|PubMed:25199835, ECO:0000269|PubMed:25344812, CC ECO:0000269|PubMed:26669264, ECO:0000269|PubMed:29973723, CC ECO:0000269|PubMed:30655953, ECO:0000269|PubMed:35045565, CC ECO:0000269|PubMed:35388221, ECO:0000269|PubMed:37535724}. CC -!- SUBUNIT: Homodimer; forms a homodimer in absence of cyclic nucleotide CC (c-di-GMP or cGAMP); 'Lys-63'-linked ubiquitination at Lys-150 is CC required for homodimerization (PubMed:22579474, PubMed:22705373, CC PubMed:22728658, PubMed:22728660, PubMed:22728659, PubMed:19285439, CC PubMed:30842659). Homotetramer; in presence of cyclic nucleotide (c-di- CC GMP or cGAMP), forms tetramers and higher-order oligomers through side- CC by-side packing (PubMed:30842653, PubMed:35388221). Interacts (when CC phosphorylated) with IRF3; following activation and phosphorylation on CC the pLxIS motif by TBK1, recruits IRF3 (PubMed:22394562, CC PubMed:25636800, PubMed:28331227, PubMed:27302953). Interacts with CC RIGI, MAVS and SSR2 (PubMed:18818105, PubMed:18724357). Interacts with CC RNF5 and TRIM56 (PubMed:19285439, PubMed:21074459). Interacts with CC TBK1; when homodimer, leading to subsequent production of IFN-beta CC (PubMed:19416887). Interacts with IFIT1 and IFIT2 (PubMed:19416887). CC Interacts with TRIM29; this interaction induces STING1 ubiquitination CC and subsequent degradation (PubMed:29038422). Associates with the MHC- CC II complex (By similarity). Interacts with STEEP1; interaction takes CC place upon cGAMP-activation and STING1 phosphorylation by MAP3K7/TAK1 CC and promotes STING1 translocation to COPII vesicles (PubMed:32690950, CC PubMed:37832545). Interacts with SEC24A, SEC24B, and SEC24C; promoting CC translocation to COPII vesicles (PubMed:32690950, PubMed:30842662). CC Interacts (when ubiquitinated) with SQSTM1; leading to relocalization CC to autophagosomes (By similarity). Interacts with SURF4 CC (PubMed:29251827). Interacts with HNRNPA2B1 (PubMed:31320558). CC Interacts with ZDHHC1; ZDHHC1 constitutively interacts with STING1 and CC in presence of DNA viruses activates it by promoting its cGAMP-induced CC oligomerization and the recruitment of downstream signaling components CC (PubMed:25299331). Interacts with ZDHHC11; in presence of DNA viruses CC promotes the recruitment of IRF3 to STING1 (PubMed:28331227). Interacts CC with TOMM70 (PubMed:20628368). Interacts with isoform IFI16-beta of CC IFI16 (PubMed:30104205). Interacts with TAB1; promoting recruitment of CC TAB1 to the endoplasmic reticulum membrane and subsequent activation of CC MAP3K7/TAK1 (PubMed:37832545). Interacts (via transmembrane domain) CC with TMEM203 (By similarity). {ECO:0000250|UniProtKB:Q3TBT3, CC ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:18818105, CC ECO:0000269|PubMed:19285439, ECO:0000269|PubMed:19416887, CC ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:21074459, CC ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:22579474, CC ECO:0000269|PubMed:22705373, ECO:0000269|PubMed:22728658, CC ECO:0000269|PubMed:22728659, ECO:0000269|PubMed:22728660, CC ECO:0000269|PubMed:25299331, ECO:0000269|PubMed:25636800, CC ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:28331227, CC ECO:0000269|PubMed:29038422, ECO:0000269|PubMed:29251827, CC ECO:0000269|PubMed:30104205, ECO:0000269|PubMed:30842659, CC ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:31320558, CC ECO:0000269|PubMed:35388221, ECO:0000269|PubMed:37832545, CC ECO:0000305|PubMed:30842653}. CC -!- SUBUNIT: (Microbial infection) Interacts with human papillomavirus CC (HPV) protein E7. {ECO:0000269|PubMed:26405230}. CC -!- SUBUNIT: (Microbial infection) Interacts with adenovirus early E1A CC protein. {ECO:0000269|PubMed:26405230}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1 CC protein ICP34.5; this interaction inhibits the intracellular DNA CC sensing pathway. {ECO:0000269|PubMed:30045990}. CC -!- SUBUNIT: (Microbial infection) Interacts with Chikungunya virus non- CC structural protein 1; this interaction results in inhibition of cGAS- CC STING signaling and increased levels of palmitoylated nsP1 and protein CC stabilization. {ECO:0000269|PubMed:33057424}. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC proteins UL94, UL42 and UL138; these interactions result in the CC inhibition of cGAS-STING signaling. {ECO:0000269|PubMed:31107917, CC ECO:0000269|PubMed:33057424, ECO:0000269|PubMed:34903048}. CC -!- SUBUNIT: (Microbial infection) Interacts with varivella virus protein CC 39; this interaction results in the inhibition of cGAS-STING signaling. CC {ECO:0000269|PubMed:36808561}. CC -!- INTERACTION: CC Q86WV6; Q96A33: CCDC47; NbExp=2; IntAct=EBI-2800345, EBI-720151; CC Q86WV6; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-2800345, EBI-11522780; CC Q86WV6; P39656: DDOST; NbExp=2; IntAct=EBI-2800345, EBI-358866; CC Q86WV6; Q16666: IFI16; NbExp=2; IntAct=EBI-2800345, EBI-2867186; CC Q86WV6; P09914: IFIT1; NbExp=3; IntAct=EBI-2800345, EBI-745117; CC Q86WV6; P09913: IFIT2; NbExp=3; IntAct=EBI-2800345, EBI-3507167; CC Q86WV6; P51617: IRAK1; NbExp=2; IntAct=EBI-2800345, EBI-358664; CC Q86WV6; O95214: LEPROTL1; NbExp=3; IntAct=EBI-2800345, EBI-750776; CC Q86WV6; O94822: LTN1; NbExp=2; IntAct=EBI-2800345, EBI-1044684; CC Q86WV6; Q7Z434: MAVS; NbExp=9; IntAct=EBI-2800345, EBI-995373; CC Q86WV6; Q7Z434-1: MAVS; NbExp=7; IntAct=EBI-2800345, EBI-15577799; CC Q86WV6; Q96N66: MBOAT7; NbExp=2; IntAct=EBI-2800345, EBI-6116499; CC Q86WV6; Q9Y342: PLLP; NbExp=3; IntAct=EBI-2800345, EBI-3919291; CC Q86WV6; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-2800345, EBI-14065960; CC Q86WV6; O95786-1: RIGI; NbExp=2; IntAct=EBI-2800345, EBI-15577823; CC Q86WV6; O95470: SGPL1; NbExp=2; IntAct=EBI-2800345, EBI-1046170; CC Q86WV6; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-2800345, EBI-12188413; CC Q86WV6; P43308: SSR2; NbExp=4; IntAct=EBI-2800345, EBI-2822012; CC Q86WV6; P42226: STAT6; NbExp=12; IntAct=EBI-2800345, EBI-1186478; CC Q86WV6; Q86WV6: STING1; NbExp=14; IntAct=EBI-2800345, EBI-2800345; CC Q86WV6; P46977: STT3A; NbExp=2; IntAct=EBI-2800345, EBI-719212; CC Q86WV6; Q13190: STX5; NbExp=3; IntAct=EBI-2800345, EBI-714206; CC Q86WV6; O15260: SURF4; NbExp=3; IntAct=EBI-2800345, EBI-1044848; CC Q86WV6; Q9UHD2: TBK1; NbExp=9; IntAct=EBI-2800345, EBI-356402; CC Q86WV6; Q9NZ01: TECR; NbExp=3; IntAct=EBI-2800345, EBI-2877718; CC Q86WV6; Q9NV29: TMEM100; NbExp=3; IntAct=EBI-2800345, EBI-8644968; CC Q86WV6; Q9BWQ6: YIPF2; NbExp=3; IntAct=EBI-2800345, EBI-751204; CC Q86WV6; PRO_0000283876 [P0C6X5]: rep; Xeno; NbExp=4; IntAct=EBI-2800345, EBI-25622115; CC Q86WV6; PRO_0000037311 [P0C6X7]: rep; Xeno; NbExp=2; IntAct=EBI-2800345, EBI-25474079; CC Q86WV6; P03255; Xeno; NbExp=2; IntAct=EBI-2800345, EBI-2603114; CC Q86WV6; PRO_0000037575 [P27958]; Xeno; NbExp=5; IntAct=EBI-2800345, EBI-8763498; CC Q86WV6; PRO_0000045601 [Q99IB8]; Xeno; NbExp=5; IntAct=EBI-2800345, EBI-6928570; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:19285439, CC ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740, CC ECO:0000269|PubMed:25254379, ECO:0000269|PubMed:29694889, CC ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, CC ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:37832545}; Multi-pass CC membrane protein {ECO:0000255, ECO:0000269|PubMed:30842659, CC ECO:0000269|PubMed:32690950}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:29694889, CC ECO:0000269|PubMed:30842653}. Endoplasmic reticulum-Golgi intermediate CC compartment membrane {ECO:0000269|PubMed:30842662, CC ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:37832545}; Multi-pass CC membrane protein {ECO:0000255, ECO:0000269|PubMed:32690950}. Golgi CC apparatus membrane {ECO:0000269|PubMed:30842653, CC ECO:0000269|PubMed:34903048, ECO:0000269|PubMed:36808561, CC ECO:0000269|PubMed:37535724}; Multi-pass membrane protein CC {ECO:0000255}. Cytoplasmic vesicle, autophagosome membrane CC {ECO:0000269|PubMed:30842662}; Multi-pass membrane protein CC {ECO:0000255}. Mitochondrion outer membrane CC {ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:19285439, CC ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740}; Multi-pass CC membrane protein {ECO:0000255}. Cell membrane CC {ECO:0000250|UniProtKB:Q3TBT3}; Multi-pass membrane protein CC {ECO:0000255}. Note=In response to double-stranded DNA stimulation, CC translocates from the endoplasmic reticulum through the endoplasmic CC reticulum-Golgi intermediate compartment and Golgi to post-Golgi CC vesicles, where the kinase TBK1 is recruited (PubMed:19433799, CC PubMed:30842659, PubMed:30842653, PubMed:29694889). Upon cGAMP-binding, CC translocates to the endoplasmic reticulum-Golgi intermediate CC compartment (ERGIC) in a process that is dependent on COPII vesicles; CC STING1-containing ERGIC serves as a membrane source for LC3 lipidation, CC which is a key step in autophagosome biogenesis (PubMed:30842662, CC PubMed:37832545). Localizes in the lysosome membrane in a TMEM203- CC dependent manner (By similarity). {ECO:0000250|UniProtKB:Q3TBT3, CC ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:29694889, CC ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, CC ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:32690950, CC ECO:0000269|PubMed:37832545}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:18724357, CC PubMed:18818105). Expressed in skin endothelial cells, alveolar type 2 CC pneumocytes, bronchial epithelium and alveolar macrophages CC (PubMed:25029335). {ECO:0000269|PubMed:18724357, CC ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:25029335}. CC -!- DOMAIN: In absence of cGAMP, the transmembrane and cytoplasmic regions CC interact to form an integrated, domain-swapped dimeric assembly (By CC similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the CC protein is autoinhibited by an intramolecular interaction between the CC cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) CC (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660, CC PubMed:22728659). Following cGAMP-binding, the cyclic dinucleotide- CC binding domain (CBD) is closed, leading to a 180 degrees rotation of CC the CBD domain relative to the transmembrane domain. This rotation is CC coupled to a conformational change in a loop on the side of the CBD CC dimer, which leads to the formation of the STING1 tetramer and higher- CC order oligomers through side-by-side packing (By similarity). The N- CC terminal part of the CBD region was initially though to contain a fifth CC transmembrane region (TM5) but is part of the folded, soluble CBD CC (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660, CC PubMed:22728659). {ECO:0000250|UniProtKB:E1C7U0, CC ECO:0000269|PubMed:22579474, ECO:0000269|PubMed:22705373, CC ECO:0000269|PubMed:22728658, ECO:0000269|PubMed:22728659, CC ECO:0000269|PubMed:22728660}. CC -!- DOMAIN: The pLxIS motif constitutes an IRF3-binding motif: following CC phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 CC recruits IRF3 (PubMed:25636800). IRF3 is then phosphorylated and CC activated by TBK1 to induce type-I interferons and other cytokines CC (PubMed:25636800). {ECO:0000269|PubMed:25636800}. CC -!- DOMAIN: The N-terminal domain interacts with glycerophospholipids and CC phospholipids. {ECO:0000269|PubMed:32690950}. CC -!- PTM: Phosphorylation by TBK1 leads to activation and production of IFN- CC beta (PubMed:18818105, PubMed:19433799, PubMed:25636800, CC PubMed:30842659, PubMed:30842653, PubMed:27302953). Following cyclic CC nucleotide (c-di-GMP or cGAMP)-binding, activation and translocation CC from the endoplasmic reticulum, STING1 is phosphorylated by TBK1 at CC Ser-366 in the pLxIS motif (PubMed:25636800, PubMed:32690950). The CC phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading CC to recruitment of the transcription factor IRF3 to induce type-I CC interferons and other cytokines (PubMed:25636800). The phosphorylated CC pLxIS motif facilitates SENP2 recruitment during late phase of viral CC infection (By similarity). Phosphorylated on tyrosine residues upon CC MHC-II aggregation (By similarity). Dephosphorylation by PPP6C leads to CC inactivation and decreased production of IFN-beta (PubMed:32753499). CC Phosphorylation at Ser-358 is also required to activate IRF3 CC (PubMed:25636800). Phosphorylation at Ser-355 by MAP3K7/TAK1 CC facilitates its interaction with STEEP1, promoting STING1 translocation CC to COPII vesicles (PubMed:37832545). {ECO:0000250|UniProtKB:Q3TBT3, CC ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, CC ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, CC ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, CC ECO:0000269|PubMed:32753499, ECO:0000269|PubMed:37832545}. CC -!- PTM: Ubiquitinated (PubMed:19285439, PubMed:19433799, PubMed:21074459, CC PubMed:25254379). Ubiquitinated via 'Lys-63'-linked ubiquitin chains in CC response to double-stranded DNA treatment, leading to relocalization to CC autophagosomes and subsequent degradation; this process is dependent on CC SQSTM1 (By similarity). 'Lys-63'-linked ubiquitination mediated by CC TRIM56 at Lys-150 promotes homodimerization and recruitment of the CC antiviral kinase TBK1 and subsequent production of IFN-beta CC (PubMed:21074459). 'Lys-48'-linked polyubiquitination at Lys-150 CC occurring after viral infection is mediated by RNF5 and leads to CC proteasomal degradation (PubMed:19285439). 'Lys-11'-linked CC polyubiquitination at Lys-150 by RNF26 leads to stabilize STING1: it CC protects STING1 from RNF5-mediated 'Lys-48'-linked polyubiquitination CC (PubMed:25254379). 'Lys-33'-linked and 'Lys-48'-linked deubiquitinated CC by USP20; leading to its stabilization and promotion of innate CC antiviral response (PubMed:27801882). 'Lys-48'-linked deubiquitinated CC by USP44; leading to its stabilization and promotion of innate CC antiviral response (PubMed:31968013). Deubiquitinated by USP13; leading CC to inhibition of innate antiviral response (PubMed:28534493). CC {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:19285439, CC ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:21074459, CC ECO:0000269|PubMed:25254379, ECO:0000269|PubMed:27801882, CC ECO:0000269|PubMed:28534493, ECO:0000269|PubMed:31968013}. CC -!- PTM: (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 CC on both 'Lys-48' and 'Lys-63'-linked ubiquitin chains; leading to CC inhibition of cGAS-STING signaling. {ECO:0000269|PubMed:36802409}. CC -!- PTM: Sumoylated at Lys-338 by TRIM38 during the early phase of viral CC infection, promoting its stability by preventing its relocalization to CC autophagosomes and subsequent degradation. Desumoylated by SENP2 during CC the late phase of viral infection. {ECO:0000250|UniProtKB:Q3TBT3}. CC -!- PTM: Palmitoylation takes place in the Golgi apparatus and creates a CC platform for the recruitment of TBK1. {ECO:0000269|PubMed:29973723}. CC -!- DISEASE: STING-associated vasculopathy, infantile-onset (SAVI) CC [MIM:615934]: An autoinflammatory disease characterized by early-onset CC systemic inflammation and cutaneous vasculopathy, resulting in severe CC skin lesions. Violaceous, scaling lesions of fingers, toes, nose, CC cheeks and ears progress to acral necrosis in most of the patients. CC Some patients have severe interstitial lung disease. CC {ECO:0000269|PubMed:25029335, ECO:0000269|PubMed:25401470, CC ECO:0000269|PubMed:30842659}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: The cGAS-STING signaling pathway drives sterile CC inflammation leading to type I interferon immunopathology in severe CC COVID-19 disease caused by SARS-CoV-2 virus infection CC (PubMed:35045565). Tissue damages in the lung and skin lesions are CC caused by activation of the cGAS-STING signaling leading to aberrant CC inflammation (PubMed:35045565). Endothelial cell damage is also caused CC by activation of the cGAS-STING pathway: SARS-CoV-2 infection triggers CC mitochondrial DNA release into the cytosol (PubMed:35045565). Released CC mitochondrial DNA is then detected by CGAS, leading to activation of CC the cGAS-STING pathway, triggering type-I interferon production and CC autoinflammation (PubMed:35045565). {ECO:0000269|PubMed:35045565}. CC -!- SIMILARITY: Belongs to the STING family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; FJ222241; ACI46648.1; -; mRNA. DR EMBL; AK290661; BAF83350.1; -; mRNA. DR EMBL; AC138517; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC047779; AAH47779.1; -; mRNA. DR CCDS; CCDS4215.1; -. DR RefSeq; NP_938023.1; NM_198282.3. DR PDB; 4EF4; X-ray; 2.15 A; A/B=139-379. DR PDB; 4EF5; X-ray; 2.45 A; A=139-379. DR PDB; 4EMT; X-ray; 1.50 A; A/B=155-341. DR PDB; 4EMU; X-ray; 1.90 A; A/B=155-341. DR PDB; 4F5D; X-ray; 3.00 A; A/B=141-379. DR PDB; 4F5E; X-ray; 2.60 A; A=141-379. DR PDB; 4F5W; X-ray; 2.20 A; A=149-379. DR PDB; 4F5Y; X-ray; 2.40 A; A/B=149-379. DR PDB; 4F9E; X-ray; 2.75 A; A=139-379. DR PDB; 4F9G; X-ray; 2.95 A; A/C=139-379. DR PDB; 4KSY; X-ray; 1.88 A; A=138-379. DR PDB; 4LOH; X-ray; 2.25 A; A/B=155-341. DR PDB; 4LOI; X-ray; 1.89 A; A/B=155-341. DR PDB; 4QXO; X-ray; 1.88 A; A=155-341. DR PDB; 4QXP; X-ray; 2.51 A; A/B=155-341. DR PDB; 4QXQ; X-ray; 2.42 A; A/B=155-341. DR PDB; 4QXR; X-ray; 2.37 A; A/B=155-341. DR PDB; 5BQX; X-ray; 2.00 A; A=138-379. DR PDB; 5JEJ; X-ray; 2.00 A; C/D/E=342-377. DR PDB; 6CFF; X-ray; 2.40 A; A=139-379. DR PDB; 6CY7; X-ray; 2.20 A; A=139-379. DR PDB; 6DNK; X-ray; 1.95 A; A=154-337. DR PDB; 6DXG; X-ray; 1.91 A; A=153-343. DR PDB; 6DXL; X-ray; 2.45 A; A/B=153-343. DR PDB; 6MX0; X-ray; 1.73 A; A/B=155-341. DR PDB; 6MX3; X-ray; 1.36 A; A/B=155-341. DR PDB; 6MXE; X-ray; 2.47 A; A/B=155-341. DR PDB; 6NT5; EM; 4.10 A; A/B=1-379. DR PDB; 6O8B; X-ray; 3.40 A; D/E=155-379. DR PDB; 6O8C; X-ray; 3.17 A; D/E=342-379. DR PDB; 6S26; X-ray; 2.05 A; A/B=140-343. DR PDB; 6S27; X-ray; 2.80 A; A=140-343. DR PDB; 6S86; X-ray; 2.60 A; A/B=140-343. DR PDB; 6UKM; X-ray; 1.74 A; A=155-341. DR PDB; 6UKU; X-ray; 1.68 A; A=155-341. DR PDB; 6UKV; X-ray; 1.83 A; A/B=155-341. DR PDB; 6UKW; X-ray; 1.97 A; A/B=155-341. DR PDB; 6UKX; X-ray; 1.93 A; A/B=155-341. DR PDB; 6UKY; X-ray; 1.95 A; A=155-341. DR PDB; 6UKZ; X-ray; 1.52 A; A/B=155-341. DR PDB; 6UL0; X-ray; 1.76 A; A=155-341. DR PDB; 6XF3; X-ray; 2.38 A; A/B=155-341. DR PDB; 6XF4; X-ray; 2.77 A; A/B=155-341. DR PDB; 6XNP; X-ray; 1.77 A; A/B=155-341. DR PDB; 6Y99; X-ray; 2.98 A; A=140-343. DR PDB; 6YDB; X-ray; 2.80 A; A=140-343. DR PDB; 6YDZ; X-ray; 2.90 A; A=140-343. DR PDB; 6YEA; X-ray; 2.81 A; A=140-343. DR PDB; 6YWA; X-ray; 2.31 A; A/B=140-343. DR PDB; 6YWB; X-ray; 2.50 A; A=140-343. DR PDB; 6Z0Z; X-ray; 2.50 A; A=140-343. DR PDB; 6Z15; X-ray; 2.50 A; A=140-343. DR PDB; 7A90; X-ray; 3.19 A; A=140-343. DR PDB; 7KVX; X-ray; 2.48 A; A=140-379. DR PDB; 7KVZ; X-ray; 2.35 A; A=140-379. DR PDB; 7KW1; X-ray; 1.80 A; A=140-379. DR PDB; 7MHC; X-ray; 2.32 A; A=154-341. DR PDB; 7OB3; X-ray; 2.30 A; A=140-343. DR PDB; 7Q3B; X-ray; 2.56 A; A=140-343. DR PDB; 7Q85; X-ray; 2.36 A; A=140-343. DR PDB; 7R4H; EM; 2.34 A; L=359-367. DR PDB; 7SHO; X-ray; 2.25 A; B=155-341. DR PDB; 7SHP; X-ray; 2.20 A; A/B/C/D=155-341. DR PDB; 7SII; EM; 3.45 A; A/B/C/D=1-344. DR PDB; 7SSM; X-ray; 1.96 A; A=155-341. DR PDB; 7T9U; X-ray; 2.46 A; A=149-345. DR PDB; 7T9V; X-ray; 2.68 A; A/B=149-345. DR PDB; 7X9P; X-ray; 2.70 A; A=150-379. DR PDB; 7X9Q; X-ray; 2.40 A; A=150-379. DR PDB; 8A2H; X-ray; 2.69 A; A/B=140-379. DR PDB; 8A2I; X-ray; 2.16 A; A/B=140-379. DR PDB; 8A2J; X-ray; 2.32 A; A/B=140-379. DR PDB; 8A2K; X-ray; 1.89 A; A/B=140-379. DR PDB; 8B2J; X-ray; 2.17 A; A/B=138-379. DR PDB; 8FLK; EM; 4.00 A; A/B/C/D=1-344. DR PDB; 8FLM; EM; 2.90 A; A/B/C/D=1-344. DR PDB; 8GJX; X-ray; 2.60 A; A/B=154-341. DR PDB; 8GSZ; EM; 3.65 A; A/B=1-379. DR PDB; 8GT6; EM; 3.47 A; A/B=1-379. DR PDB; 8IK3; EM; 3.30 A; A/B/C/D/E/F/G/H=1-379. DR PDB; 8STH; X-ray; 1.97 A; A=153-339. DR PDB; 8STI; X-ray; 1.72 A; A=153-339. DR PDB; 8T5K; X-ray; 1.95 A; B=154-341. DR PDB; 8T5L; X-ray; 2.01 A; B=154-341. DR PDBsum; 4EF4; -. DR PDBsum; 4EF5; -. DR PDBsum; 4EMT; -. DR PDBsum; 4EMU; -. DR PDBsum; 4F5D; -. DR PDBsum; 4F5E; -. DR PDBsum; 4F5W; -. DR PDBsum; 4F5Y; -. DR PDBsum; 4F9E; -. DR PDBsum; 4F9G; -. DR PDBsum; 4KSY; -. DR PDBsum; 4LOH; -. DR PDBsum; 4LOI; -. DR PDBsum; 4QXO; -. DR PDBsum; 4QXP; -. DR PDBsum; 4QXQ; -. DR PDBsum; 4QXR; -. DR PDBsum; 5BQX; -. DR PDBsum; 5JEJ; -. DR PDBsum; 6CFF; -. DR PDBsum; 6CY7; -. DR PDBsum; 6DNK; -. DR PDBsum; 6DXG; -. DR PDBsum; 6DXL; -. DR PDBsum; 6MX0; -. DR PDBsum; 6MX3; -. DR PDBsum; 6MXE; -. DR PDBsum; 6NT5; -. DR PDBsum; 6O8B; -. DR PDBsum; 6O8C; -. DR PDBsum; 6S26; -. DR PDBsum; 6S27; -. DR PDBsum; 6S86; -. DR PDBsum; 6UKM; -. DR PDBsum; 6UKU; -. DR PDBsum; 6UKV; -. DR PDBsum; 6UKW; -. DR PDBsum; 6UKX; -. DR PDBsum; 6UKY; -. DR PDBsum; 6UKZ; -. DR PDBsum; 6UL0; -. DR PDBsum; 6XF3; -. DR PDBsum; 6XF4; -. DR PDBsum; 6XNP; -. DR PDBsum; 6Y99; -. DR PDBsum; 6YDB; -. DR PDBsum; 6YDZ; -. DR PDBsum; 6YEA; -. DR PDBsum; 6YWA; -. DR PDBsum; 6YWB; -. DR PDBsum; 6Z0Z; -. DR PDBsum; 6Z15; -. DR PDBsum; 7A90; -. DR PDBsum; 7KVX; -. DR PDBsum; 7KVZ; -. DR PDBsum; 7KW1; -. DR PDBsum; 7MHC; -. DR PDBsum; 7OB3; -. DR PDBsum; 7Q3B; -. DR PDBsum; 7Q85; -. DR PDBsum; 7R4H; -. DR PDBsum; 7SHO; -. DR PDBsum; 7SHP; -. DR PDBsum; 7SII; -. DR PDBsum; 7SSM; -. DR PDBsum; 7T9U; -. DR PDBsum; 7T9V; -. DR PDBsum; 7X9P; -. DR PDBsum; 7X9Q; -. DR PDBsum; 8A2H; -. DR PDBsum; 8A2I; -. DR PDBsum; 8A2J; -. DR PDBsum; 8A2K; -. DR PDBsum; 8B2J; -. DR PDBsum; 8FLK; -. DR PDBsum; 8FLM; -. DR PDBsum; 8GJX; -. DR PDBsum; 8GSZ; -. DR PDBsum; 8GT6; -. DR PDBsum; 8IK3; -. DR PDBsum; 8STH; -. DR PDBsum; 8STI; -. DR PDBsum; 8T5K; -. DR PDBsum; 8T5L; -. DR AlphaFoldDB; Q86WV6; -. DR EMDB; EMD-0502; -. DR EMDB; EMD-25142; -. DR EMDB; EMD-29281; -. DR EMDB; EMD-29282; -. DR EMDB; EMD-34244; -. DR EMDB; EMD-34245; -. DR SMR; Q86WV6; -. DR BioGRID; 130988; 109. DR ComplexPortal; CPX-2127; STING complex. DR ComplexPortal; CPX-6018; STING-TRAF3-TBK1 complex. DR CORUM; Q86WV6; -. DR DIP; DIP-48847N; -. DR IntAct; Q86WV6; 81. DR STRING; 9606.ENSP00000498596; -. DR BindingDB; Q86WV6; -. DR ChEMBL; CHEMBL4523377; -. DR GuidetoPHARMACOLOGY; 2902; -. DR TCDB; 1.A.140.1.1; the stimulator of interferon genes protein (sting) family. DR iPTMnet; Q86WV6; -. DR PhosphoSitePlus; Q86WV6; -. DR SwissPalm; Q86WV6; -. DR BioMuta; TMEM173; -. DR DMDM; 74727720; -. DR EPD; Q86WV6; -. DR jPOST; Q86WV6; -. DR MassIVE; Q86WV6; -. DR MaxQB; Q86WV6; -. DR PaxDb; 9606-ENSP00000331288; -. DR PeptideAtlas; Q86WV6; -. DR ProteomicsDB; 70211; -. DR Pumba; Q86WV6; -. DR Antibodypedia; 26796; 917 antibodies from 42 providers. DR CPTC; Q86WV6; 1 antibody. DR DNASU; 340061; -. DR Ensembl; ENST00000330794.9; ENSP00000331288.4; ENSG00000184584.14. DR Ensembl; ENST00000651699.1; ENSP00000499166.1; ENSG00000184584.14. DR Ensembl; ENST00000652271.1; ENSP00000498596.1; ENSG00000184584.14. DR Ensembl; ENST00000672096.1; ENSP00000500685.1; ENSG00000288243.1. DR Ensembl; ENST00000672102.1; ENSP00000500793.1; ENSG00000288243.1. DR Ensembl; ENST00000672865.1; ENSP00000500823.1; ENSG00000288243.1. DR GeneID; 340061; -. DR KEGG; hsa:340061; -. DR MANE-Select; ENST00000330794.9; ENSP00000331288.4; NM_198282.4; NP_938023.1. DR UCSC; uc003lep.4; human. DR AGR; HGNC:27962; -. DR CTD; 340061; -. DR DisGeNET; 340061; -. DR GeneCards; STING1; -. DR HGNC; HGNC:27962; STING1. DR HPA; ENSG00000184584; Low tissue specificity. DR MalaCards; STING1; -. DR MIM; 612374; gene. DR MIM; 615934; phenotype. DR neXtProt; NX_Q86WV6; -. DR OpenTargets; ENSG00000184584; -. DR Orphanet; 481662; Familial Chilblain lupus. DR Orphanet; 425120; STING-associated vasculopathy with onset in infancy. DR VEuPathDB; HostDB:ENSG00000184584; -. DR eggNOG; ENOG502R15M; Eukaryota. DR GeneTree; ENSGT00390000008582; -. DR HOGENOM; CLU_062449_0_0_1; -. DR InParanoid; Q86WV6; -. DR OMA; QYGQAGF; -. DR OrthoDB; 5352585at2759; -. DR PhylomeDB; Q86WV6; -. DR TreeFam; TF324444; -. DR PathwayCommons; Q86WV6; -. DR Reactome; R-HSA-1834941; STING mediated induction of host immune responses. DR Reactome; R-HSA-3134975; Regulation of innate immune responses to cytosolic DNA. DR Reactome; R-HSA-3249367; STAT6-mediated induction of chemokines. DR Reactome; R-HSA-3270619; IRF3-mediated induction of type I IFN. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9692916; SARS-CoV-1 activates/modulates innate immune responses. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR SignaLink; Q86WV6; -. DR SIGNOR; Q86WV6; -. DR BioGRID-ORCS; 340061; 13 hits in 1159 CRISPR screens. DR ChiTaRS; TMEM173; human. DR GenomeRNAi; 340061; -. DR Pharos; Q86WV6; Tchem. DR PRO; PR:Q86WV6; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q86WV6; Protein. DR Bgee; ENSG00000184584; Expressed in right uterine tube and 98 other cell types or tissues. DR ExpressionAtlas; Q86WV6; baseline and differential. DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB. DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB. DR GO; GO:0005777; C:peroxisome; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome. DR GO; GO:1902554; C:serine/threonine protein kinase complex; NAS:ComplexPortal. DR GO; GO:1990231; C:STING complex; IPI:ComplexPortal. DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; IDA:UniProtKB. DR GO; GO:0035438; F:cyclic-di-GMP binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IDA:BHF-UCL. DR GO; GO:0015252; F:proton channel activity; IDA:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IDA:BHF-UCL. DR GO; GO:0035591; F:signaling adaptor activity; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl. DR GO; GO:0002218; P:activation of innate immune response; IDA:ComplexPortal. DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProt. DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProtKB. DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IMP:BHF-UCL. DR GO; GO:0035458; P:cellular response to interferon-beta; IEA:Ensembl. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:UniProtKB. DR GO; GO:0140896; P:cGAS/STING signaling pathway; IDA:UniProtKB. DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB. DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IDA:UniProt. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:BHF-UCL. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:UniProtKB. DR GO; GO:0016239; P:positive regulation of macroautophagy; IDA:UniProtKB. DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0032481; P:positive regulation of type I interferon production; IDA:UniProtKB. DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IDA:ComplexPortal. DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0061709; P:reticulophagy; ISS:UniProtKB. DR CDD; cd22658; STING_C_metazoan-like; 1. DR DisProt; DP01602; -. DR Gene3D; 1.20.5.5200; -; 1. DR Gene3D; 3.40.50.12100; Stimulator of interferon genes protein; 1. DR InterPro; IPR029158; STING. DR InterPro; IPR047191; STING_C_chordates. DR InterPro; IPR038623; STING_C_sf. DR PANTHER; PTHR34339; STIMULATOR OF INTERFERON GENES PROTEIN; 1. DR PANTHER; PTHR34339:SF1; STIMULATOR OF INTERFERON GENES PROTEIN; 1. DR Pfam; PF15009; TMEM173; 1. DR Genevisible; Q86WV6; HS. PE 1: Evidence at protein level; KW 3D-structure; Autophagy; Cell membrane; Cytoplasm; Cytoplasmic vesicle; KW Disease variant; Endoplasmic reticulum; Golgi apparatus; KW Host-virus interaction; Immunity; Innate immunity; Ion channel; KW Ion transport; Isopeptide bond; Lipoprotein; Membrane; Mitochondrion; KW Mitochondrion outer membrane; Nucleotide-binding; Palmitate; KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix; KW Transport; Ubl conjugation. FT CHAIN 1..379 FT /note="Stimulator of interferon genes protein" FT /id="PRO_0000271116" FT TOPO_DOM 1..17 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30842659" FT TRANSMEM 18..34 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:30842659" FT TOPO_DOM 35..44 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:30842659" FT TRANSMEM 45..69 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:30842659" FT TOPO_DOM 70..91 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30842659" FT TRANSMEM 92..106 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:30842659" FT TOPO_DOM 107..116 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:30842659" FT TRANSMEM 117..134 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:30842659" FT TOPO_DOM 135..379 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30842659" FT REGION 1..190 FT /note="Mediates interaction with ZDHHC1 and ZDHHC11" FT /evidence="ECO:0000269|PubMed:25299331, FT ECO:0000269|PubMed:28331227" FT REGION 153..340 FT /note="Cyclic dinucleotide-binding domain (CBD)" FT /evidence="ECO:0000269|PubMed:22705373" FT REGION 340..379 FT /note="C-terminal tail (CTT)" FT /evidence="ECO:0000269|PubMed:22705373" FT REGION 341..370 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 363..366 FT /note="pLxIS motif" FT /evidence="ECO:0000269|PubMed:25636800" FT COMPBIAS 346..362 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 162 FT /ligand="2',3'-cGAMP" FT /ligand_id="ChEBI:CHEBI:143093" FT /evidence="ECO:0000269|PubMed:23910378, FT ECO:0000269|PubMed:35388221, ECO:0007744|PDB:4LOH, FT ECO:0007744|PDB:7SII" FT BINDING 162 FT /ligand="3',3'-c-di-GMP" FT /ligand_id="ChEBI:CHEBI:58805" FT /evidence="ECO:0000269|PubMed:22728660, FT ECO:0007744|PDB:4F5Y" FT BINDING 167 FT /ligand="2',3'-cGAMP" FT /ligand_id="ChEBI:CHEBI:143093" FT /evidence="ECO:0000269|PubMed:23747010, FT ECO:0000269|PubMed:23910378, ECO:0007744|PDB:4KSY, FT ECO:0007744|PDB:4LOH" FT BINDING 167 FT /ligand="2',3'-cUAMP" FT /ligand_id="ChEBI:CHEBI:228269" FT /evidence="ECO:0000269|PubMed:37379839, FT ECO:0007744|PDB:8GJX" FT BINDING 167 FT /ligand="3',3'-c-di-GMP" FT /ligand_id="ChEBI:CHEBI:58805" FT /evidence="ECO:0000269|PubMed:22579474, FT ECO:0000269|PubMed:22705373, ECO:0000269|PubMed:22728658, FT ECO:0000269|PubMed:22728659, ECO:0000269|PubMed:22728660, FT ECO:0007744|PDB:4EF4, ECO:0007744|PDB:4EMT, FT ECO:0007744|PDB:4F5D, ECO:0007744|PDB:4F5Y, FT ECO:0007744|PDB:4F9G" FT BINDING 238..241 FT /ligand="3',3'-c-di-GMP" FT /ligand_id="ChEBI:CHEBI:58805" FT /evidence="ECO:0000269|PubMed:22728658, FT ECO:0000269|PubMed:22728659, ECO:0000269|PubMed:22728660, FT ECO:0007744|PDB:4EMT, ECO:0007744|PDB:4F5D, FT ECO:0007744|PDB:4F5Y" FT BINDING 238 FT /ligand="2',3'-cGAMP" FT /ligand_id="ChEBI:CHEBI:143093" FT /evidence="ECO:0000269|PubMed:23747010, FT ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:35388221, FT ECO:0007744|PDB:4KSY, ECO:0007744|PDB:4LOH, FT ECO:0007744|PDB:7SII" FT BINDING 238 FT /ligand="2',3'-cUAMP" FT /ligand_id="ChEBI:CHEBI:228269" FT /evidence="ECO:0000269|PubMed:37379839, FT ECO:0007744|PDB:8GJX" FT BINDING 263 FT /ligand="2',3'-cGAMP" FT /ligand_id="ChEBI:CHEBI:143093" FT /evidence="ECO:0000269|PubMed:23747010, FT ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:35388221, FT ECO:0007744|PDB:4KSY, ECO:0007744|PDB:4LOH, FT ECO:0007744|PDB:7SII" FT BINDING 263 FT /ligand="2',3'-cUAMP" FT /ligand_id="ChEBI:CHEBI:228269" FT /evidence="ECO:0000269|PubMed:37379839, FT ECO:0007744|PDB:8GJX" FT BINDING 263 FT /ligand="3',3'-c-di-GMP" FT /ligand_id="ChEBI:CHEBI:58805" FT /evidence="ECO:0000269|PubMed:22579474, FT ECO:0000269|PubMed:22705373, ECO:0000269|PubMed:22728658, FT ECO:0000269|PubMed:22728660, ECO:0007744|PDB:4EF4, FT ECO:0007744|PDB:4EMT, ECO:0007744|PDB:4F5Y, FT ECO:0007744|PDB:4F9G" FT MOD_RES 229 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:37832545" FT MOD_RES 241 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:37832545" FT MOD_RES 354 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:37832545" FT MOD_RES 355 FT /note="Phosphoserine; by MAP3K7" FT /evidence="ECO:0000269|PubMed:37832545" FT MOD_RES 356 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:37832545" FT MOD_RES 358 FT /note="Phosphoserine; by TBK1" FT /evidence="ECO:0000269|PubMed:18818105, FT ECO:0000269|PubMed:25636800" FT MOD_RES 366 FT /note="Phosphoserine; by TBK1" FT /evidence="ECO:0000269|PubMed:25636800, FT ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:32753499" FT LIPID 88 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:Q3TBT3" FT LIPID 91 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:29973723" FT CROSSLNK 150 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:19285439, FT ECO:0000269|PubMed:21074459" FT CROSSLNK 236 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:31968013" FT CROSSLNK 338 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250|UniProtKB:Q3TBT3" FT VARIANT 71 FT /note="R -> H (in dbSNP:rs11554776)" FT /id="VAR_029863" FT VARIANT 147 FT /note="V -> L (in SAVI; dbSNP:rs587777611)" FT /evidence="ECO:0000269|PubMed:25029335" FT /id="VAR_071878" FT VARIANT 154 FT /note="N -> S (in SAVI; dbSNP:rs587777609)" FT /evidence="ECO:0000269|PubMed:25029335" FT /id="VAR_071879" FT VARIANT 155 FT /note="V -> M (in SAVI; constitutively active mutant that FT promotes the production of type I interferon in absence of FT cGAMP ligand; dbSNP:rs587777610)" FT /evidence="ECO:0000269|PubMed:25029335, FT ECO:0000269|PubMed:25401470, ECO:0000269|PubMed:30842659" FT /id="VAR_071880" FT VARIANT 232 FT /note="H -> R (activated by both 2'-3' linked cGAMP and FT 3'-3' linked cGAMP; dbSNP:rs1131769)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:26300263" FT /id="VAR_029864" FT VARIANT 284 FT /note="R -> S (found in a 9-month-old patient who died FT following a fever and severe neck abscess without FT indication of any severe bacterial infection; likely FT pathogenic; may affect splicing; constitutively active FT mutant that promotes the production of type I interferon in FT absence of cyclic dinucleotide ligand; localizes to the FT perinuclear region in absence of cyclic dinucleotide FT ligand)" FT /evidence="ECO:0000269|PubMed:29694889" FT /id="VAR_081660" FT VARIANT 293 FT /note="R -> Q (in dbSNP:rs7380824)" FT /id="VAR_029865" FT MUTAGEN 10 FT /note="I->Q: Abolished ability to induce the production of FT type I interferon." FT /evidence="ECO:0000269|PubMed:30842659" FT MUTAGEN 14 FT /note="R->A: Abolished ability to induce the production of FT type I interferon." FT /evidence="ECO:0000269|PubMed:30842659" FT MUTAGEN 20 FT /note="K->R: Does not affect amount of ubiquitination." FT /evidence="ECO:0000269|PubMed:21074459" FT MUTAGEN 26 FT /note="L->A: Reduced homooligomerization and activation in FT presence of coumpond C53." FT /evidence="ECO:0000269|PubMed:35388221" FT MUTAGEN 30 FT /note="L->A: Reduced homooligomerization and activation in FT presence of coumpond C53." FT /evidence="ECO:0000269|PubMed:35388221" FT MUTAGEN 44 FT /note="L->A: Reduced homooligomerization and activation in FT presence of coumpond C53." FT /evidence="ECO:0000269|PubMed:35388221" FT MUTAGEN 68 FT /note="E->A: Abolished ability to induce the production of FT type I interferon." FT /evidence="ECO:0000269|PubMed:30842659" FT MUTAGEN 69 FT /note="E->A: Abolished ability to induce the production of FT type I interferon." FT /evidence="ECO:0000269|PubMed:30842659" FT MUTAGEN 76..78 FT /note="RYR->AYA: Abolishes the endoplasmic reticulum FT location." FT /evidence="ECO:0000269|PubMed:19433799" FT MUTAGEN 91 FT /note="C->S: Abolished inhibition by small-molecule H-151; FT abolished palmitoylation." FT /evidence="ECO:0000269|PubMed:29973723" FT MUTAGEN 104 FT /note="Y->A: Reduced homooligomerization and activation in FT presence of coumpond C53." FT /evidence="ECO:0000269|PubMed:35388221" FT MUTAGEN 137 FT /note="K->R: Does not affect amount of ubiquitination." FT /evidence="ECO:0000269|PubMed:21074459" FT MUTAGEN 150 FT /note="K->R: Abolishes ubiquitination, homodimerization and FT subsequent production of IFN-beta." FT /evidence="ECO:0000269|PubMed:19285439, FT ECO:0000269|PubMed:21074459, ECO:0000269|PubMed:25254379" FT MUTAGEN 153 FT /note="F->A: Partially constitutively active mutant that FT promotes the production of type I interferon in absence of FT cGAMP ligand." FT /evidence="ECO:0000269|PubMed:30842659" FT MUTAGEN 158 FT /note="G->A: Constitutively active mutant that promotes the FT production of type I interferon in absence of cGAMP FT ligand." FT /evidence="ECO:0000269|PubMed:30842659" FT MUTAGEN 158 FT /note="G->E: Abolished homodimerization and activation." FT /evidence="ECO:0000269|PubMed:37832545" FT MUTAGEN 158 FT /note="G->S,V: Partially constitutively active mutant that FT promotes the production of type I interferon in absence of FT cGAMP ligand." FT /evidence="ECO:0000269|PubMed:30842659" FT MUTAGEN 162 FT /note="S->A: Slight decrease in c-di-GMP-binding. Renders FT the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic FT acid (DMXAA) drug, leading to activation of the STING1 FT pathway. Renders the enzyme sensitive to FT 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug; when FT associated with I-266." FT /evidence="ECO:0000269|PubMed:22728658, FT ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:25199835, FT ECO:0000269|PubMed:26669264" FT MUTAGEN 166 FT /note="G->S: Slight decrease in c-di-GMP-binding." FT /evidence="ECO:0000269|PubMed:22728658" FT MUTAGEN 178..180 FT /note="RIR->AIA: Abolishes the endoplasmic reticulum FT location." FT /evidence="ECO:0000269|PubMed:19433799" FT MUTAGEN 230 FT /note="G->I: Renders the enzyme sensitive to FT 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading FT to activation of the STING1 pathway." FT /evidence="ECO:0000269|PubMed:25199835" FT MUTAGEN 236 FT /note="K->R: Loss of deubiquitination by USP44." FT /evidence="ECO:0000269|PubMed:31968013" FT MUTAGEN 238..240 FT /note="RVY->AVA: Strong decrease in cGAMP-binding without FT affecting interaction with TBK1. Abolished ability to FT induce autophagy." FT /evidence="ECO:0000269|PubMed:30842653, FT ECO:0000269|PubMed:30842662" FT MUTAGEN 238 FT /note="R->A: Abolished cGAMP-binding. Abolished ability to FT induce autophagy." FT /evidence="ECO:0000269|PubMed:23910378, FT ECO:0000269|PubMed:30842662" FT MUTAGEN 240 FT /note="Y->A: Abolished cGAMP-binding." FT /evidence="ECO:0000269|PubMed:23910378" FT MUTAGEN 240 FT /note="Y->S: Strong decrease in c-di-GMP-binding." FT /evidence="ECO:0000269|PubMed:22728658" FT MUTAGEN 242 FT /note="N->A: Strong decrease in c-di-GMP and FT cGAMP-binding." FT /evidence="ECO:0000269|PubMed:22728658, FT ECO:0000269|PubMed:23910378" FT MUTAGEN 260 FT /note="E->A: Strong decrease in c-di-GMP and FT cGAMP-binding." FT /evidence="ECO:0000269|PubMed:22728658, FT ECO:0000269|PubMed:23910378" FT MUTAGEN 263 FT /note="T->A: Strong decrease in c-di-GMP-binding." FT /evidence="ECO:0000269|PubMed:22728658" FT MUTAGEN 264 FT /note="P->A: Strong decrease in c-di-GMP-binding." FT /evidence="ECO:0000269|PubMed:22728658" FT MUTAGEN 266 FT /note="Q->I: Renders the enzyme sensitive to FT 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading FT to activation of the STING1 pathway; when associated with FT A-162." FT /evidence="ECO:0000269|PubMed:25199835" FT MUTAGEN 267 FT /note="T->A: Strong decrease in c-di-GMP-binding." FT /evidence="ECO:0000269|PubMed:22728658" FT MUTAGEN 273..277 FT /note="QYSQA->AYSQQ: In AQQA mutant reduced FT homooligomerization and ability to induce type I FT interferons. Abrogates interaction with STEEP." FT /evidence="ECO:0000269|PubMed:32690950, FT ECO:0000269|PubMed:37535724" FT MUTAGEN 273 FT /note="Q->A: Abolished translocation from the endoplasmic FT reticulum in response to cGAMP-binding. Reduced FT phosphorylation by TBK1." FT /evidence="ECO:0000269|PubMed:30842653, FT ECO:0000269|PubMed:30842659" FT MUTAGEN 277 FT /note="A->Q: Abolished translocation from the endoplasmic FT reticulum in response to cGAMP-binding. Reduced FT phosphorylation by TBK1." FT /evidence="ECO:0000269|PubMed:30842653, FT ECO:0000269|PubMed:30842659" FT MUTAGEN 324..326 FT /note="SLS->ALA: Induces a decrease in phosphorylation by FT TBK1." FT /evidence="ECO:0000269|PubMed:18818105" FT MUTAGEN 333..334 FT /note="LR->AA: Abolished ability to induce autophagy. FT Abolished interaction with SEC24C." FT /evidence="ECO:0000269|PubMed:30842662" FT MUTAGEN 341 FT /note="V->A: Does not affect ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:22394562" FT MUTAGEN 342 FT /note="T->A: Does not affect ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:22394562" FT MUTAGEN 355 FT /note="S->A: Impaired ability to induce the production of FT type I interferon." FT /evidence="ECO:0000269|PubMed:37832545" FT MUTAGEN 358 FT /note="S->A: Decreased phosphorylation by TBK1, leading to FT reduced ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:18818105, FT ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:25636800, FT ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:29478775" FT MUTAGEN 360 FT /note="E->A: Does not affect ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:22394562" FT MUTAGEN 362 FT /note="E->A: Slightly affects ability to induce the FT production of type I interferon." FT /evidence="ECO:0000269|PubMed:27302953" FT MUTAGEN 363 FT /note="L->A: Abolished ability to induce the production of FT type I interferon." FT /evidence="ECO:0000269|PubMed:27302953" FT MUTAGEN 364 FT /note="L->A: Slightly affects ability to induce the FT production of type I interferon." FT /evidence="ECO:0000269|PubMed:27302953" FT MUTAGEN 365 FT /note="I->A: Abolished ability to induce the production of FT type I interferon." FT /evidence="ECO:0000269|PubMed:27302953" FT MUTAGEN 366 FT /note="S->A,N,C: Induces a decrease in phosphorylation by FT TBK1. Abolished ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:22394562, FT ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953" FT MUTAGEN 366 FT /note="S->D: Phosphomimetic mutant; retains some ability to FT activate IRF3. It probably incompletely mimics FT phosphorylation." FT /evidence="ECO:0000269|PubMed:25636800" FT MUTAGEN 367 FT /note="G->A: Does not affect ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:22394562" FT MUTAGEN 371 FT /note="P->Q: Abolished ability to induce the production of FT type I interferon." FT /evidence="ECO:0000269|PubMed:30842653" FT MUTAGEN 374 FT /note="L->A: Abolished ability to activate IRF3 and induce FT the production of type I interferon." FT /evidence="ECO:0000269|PubMed:22394562, FT ECO:0000269|PubMed:30842653" FT MUTAGEN 375 FT /note="R->A: Does not affect ability to activate IRF3. FT Abolished ability to induce the production of type I FT interferon." FT /evidence="ECO:0000269|PubMed:22394562, FT ECO:0000269|PubMed:30842653" FT MUTAGEN 376 FT /note="T->A: Does not affect ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:27302953" FT MUTAGEN 377 FT /note="D->A: Does not affect ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:22394562" FT MUTAGEN 379 FT /note="S->A: Does not affect ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:27302953" FT CONFLICT 262 FT /note="A -> T (in Ref. 2; BAF83350)" FT /evidence="ECO:0000305" FT CONFLICT 363 FT /note="L -> F (in Ref. 2; BAF83350)" FT /evidence="ECO:0000305" FT HELIX 17..36 FT /evidence="ECO:0007829|PDB:7SII" FT HELIX 40..69 FT /evidence="ECO:0007829|PDB:7SII" FT HELIX 70..72 FT /evidence="ECO:0007829|PDB:7SII" FT TURN 73..79 FT /evidence="ECO:0007829|PDB:7SII" FT HELIX 81..89 FT /evidence="ECO:0007829|PDB:7SII" FT HELIX 92..108 FT /evidence="ECO:0007829|PDB:7SII" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:7SII" FT HELIX 117..134 FT /evidence="ECO:0007829|PDB:7SII" FT HELIX 141..151 FT /evidence="ECO:0007829|PDB:7SII" FT HELIX 156..166 FT /evidence="ECO:0007829|PDB:6MX3" FT HELIX 168..185 FT /evidence="ECO:0007829|PDB:6MX3" FT TURN 186..189 FT /evidence="ECO:0007829|PDB:4EMT" FT HELIX 190..192 FT /evidence="ECO:0007829|PDB:6UKM" FT STRAND 196..203 FT /evidence="ECO:0007829|PDB:6MX3" FT HELIX 212..215 FT /evidence="ECO:0007829|PDB:4EMT" FT STRAND 219..224 FT /evidence="ECO:0007829|PDB:6MX3" FT STRAND 228..232 FT /evidence="ECO:0007829|PDB:6UKZ" FT STRAND 235..240 FT /evidence="ECO:0007829|PDB:6UKZ" FT STRAND 243..249 FT /evidence="ECO:0007829|PDB:6MX3" FT STRAND 252..261 FT /evidence="ECO:0007829|PDB:6MX3" FT HELIX 265..272 FT /evidence="ECO:0007829|PDB:6MX3" FT HELIX 275..277 FT /evidence="ECO:0007829|PDB:6MX3" FT HELIX 281..301 FT /evidence="ECO:0007829|PDB:6MX3" FT HELIX 303..306 FT /evidence="ECO:0007829|PDB:4EMT" FT STRAND 309..314 FT /evidence="ECO:0007829|PDB:6MX3" FT STRAND 317..319 FT /evidence="ECO:0007829|PDB:7X9Q" FT HELIX 320..322 FT /evidence="ECO:0007829|PDB:6XNP" FT HELIX 325..335 FT /evidence="ECO:0007829|PDB:6MX3" FT HELIX 372..374 FT /evidence="ECO:0007829|PDB:5JEJ" SQ SEQUENCE 379 AA; 42193 MW; CB54D6A4D4D8E7C0 CRC64; MPHSSLHPSI PCPRGHGAQK AALVLLSACL VTLWGLGEPP EHTLRYLVLH LASLQLGLLL NGVCSLAEEL RHIHSRYRGS YWRTVRACLG CPLRRGALLL LSIYFYYSLP NAVGPPFTWM LALLGLSQAL NILLGLKGLA PAEISAVCEK GNFNVAHGLA WSYYIGYLRL ILPELQARIR TYNQHYNNLL RGAVSQRLYI LLPLDCGVPD NLSMADPNIR FLDKLPQQTG DHAGIKDRVY SNSIYELLEN GQRAGTCVLE YATPLQTLFA MSQYSQAGFS REDRLEQAKL FCRTLEDILA DAPESQNNCR LIAYQEPADD SSFSLSQEVL RHLRQEEKEE VTVGSLKTSA VPSTSTMSQE PELLISGMEK PLPLRTDFS //